bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluating homophily in networks via HONTO (HOmophily Network TOol): a case study of chromosomal interactions in human PPI networks
Authors: Apollonio Nicola , Blankenberg Daniel , Cumbo Fabio , Franciosa Paolo Giulio , Santoni Daniele
Published: November 2022

It has been observed in different kinds of networks, such as social or biological ones, a typical behavior inspired by the general principle ‘similarity breeds connections’. These networks are defined as homophilic as nodes belonging to the same class preferentially interact with each other. In this work, we present HONTO (HOmophily Network TOol), a user-friendly open-source Python3 package designed to evaluate and analyze homophily in complex networks. The tool takes in input from the network along with a partition of its nodes into classes and yields a matrix whose entries are the homophily/heterophily z-score values. To complement the analysis, the tool also provides z-score values of nodes that do not interact with any other node of the same class. Homophily/heterophily z-scores values are presented as a heatmap allowing a visual at-a-glance interpretation of results.

Availability and implementation

Tool’s source code is available at https://github.com/cumbof/honto under the MIT license, installable as a package from PyPI (pip install honto) and conda-forge (conda install -c conda-forge honto), and has a wrapper for the Galaxy platform available on the official Galaxy ToolShed (Blankenberg et al., 2014) at https://toolshed.g2.bx.psu.edu/view/fabio/honto.
Mitochondria as disease-relevant organelles in rheumatoid arthritis
Authors: Weyand Cornelia M , Wu Bowen , Huang Tao , Hu Zhaolan , Goronzy Jörg J
Published: November 2022

Mitochondria are the controllers of cell metabolism and are recognized as decision makers in cell death pathways, organizers of cytoplasmic signaling networks, managers of cellular stress responses, and regulators of nuclear gene expression. Cells of the immune system are particularly dependent on mitochondrial resources, as they must swiftly respond to danger signals with activation, trafficking, migration, and generation of daughter cells. Analogously, faulty immune responses that lead to autoimmunity and tissue inflammation rely on mitochondria to supply energy, cell building blocks and metabolic intermediates. Emerging data endorse the concept that mitochondrial fitness, and the lack of it, is of particular relevance in the autoimmune disease rheumatoid arthritis (RA) where deviations of bioenergetic and biosynthetic flux affect T cells during early and late stages of disease. During early stages of RA, mitochondrial deficiency allows naïve RA T cells to lose self-tolerance, biasing fundamental choices of the immune system toward immune-mediated tissue damage and away from host protection. During late stages of RA, mitochondrial abnormalities shape the response patterns of RA effector T cells engaged in the inflammatory lesions, enabling chronicity of tissue damage and tissue remodeling. In the inflamed joint, autoreactive T cells partner with metabolically reprogrammed tissue macrophages that specialize in antigen-presentation and survive by adapting to the glucose-deplete tissue microenvironment. Here, we summarize recent data on dysfunctional mitochondria and mitochondria-derived signals relevant in the RA disease process that offer novel opportunities to deter autoimmune tissue inflammation by metabolic interference.
Functional reconfiguration of task-active frontoparietal control network facilitates abstract reasoning
Authors: Morin Thomas M , Moore Kylie N , Isenburg Kylie , Ma Weida , Stern Chantal E
Published: November 2022

While the brain’s functional network architecture is largely conserved between resting and task states, small but significant changes in functional connectivity support complex cognition. In this study, we used a modified Raven’s Progressive Matrices Task to examine symbolic and perceptual reasoning in human participants undergoing fMRI scanning. Previously, studies have focused predominantly on discrete symbolic versions of matrix reasoning, even though the first few trials of the Raven’s Advanced Progressive Matrices task consist of continuous perceptual stimuli. Our analysis examined the activation patterns and functional reconfiguration of brain networks associated with resting state and both symbolic and perceptual reasoning. We found that frontoparietal networks, including the cognitive control and dorsal attention networks, were significantly activated during abstract reasoning. We determined that these same task-active regions exhibited flexibly-reconfigured functional connectivity when transitioning from resting state to the abstract reasoning task. Conversely, we showed that a stable network core of regions in default and somatomotor networks was maintained across both resting and task states. We propose that these regionally-specific changes in the functional connectivity of frontoparietal networks puts the brain in a “task-ready” state, facilitating efficient task-based activation.
How Fiscal Rules Matter for Successful Fiscal Consolidations: New Evidence
Authors: Aaskoven Lasse , Wiese Rasmus
Published: November 2022

Fiscal rules are increasingly promoted by international organizations. We investigate whether fiscal rules are effective in achieving sustained debt reduction during periods of fiscal consolidation using data from 19 OECD countries. The analysis is based on an extended version of the International Monetary Fund’s fiscal rules database. Fiscal consolidation periods are identified using a novel method that takes differences in the variability of fiscal balances into account. We find: (i) the EU’s Stability and Growth Pact is associated with sustained debt reduction while it is more doubtful if the mere existence of national fiscal rules has an effect. (ii) Fiscal rules have a stronger association with sustained debt reduction when they are embedded in a stricter national institutional framework (JEL codes: H6).
Prevalence, Distribution, and Characteristics Associated With Possession of Buprenorphine Waivers Among Infectious Diseases Physicians in the United States
Authors: Fujita Ayako Wendy , Loughry Nora , Moore DeLante E , Carter Andrea E , Hussen Sophia A , Cooper Hannah , Colasanti Jonathan A , Sheth Anandi N
Published: November 2022

Background

Persons with opioid use disorder (OUD) may present with infectious complications from injection drug use; thus, infectious diseases (ID) physicians are uniquely positioned to treat OUD. Buprenorphine is safe and effective for OUD but remains underutilized. The prevalence and geographic distribution of ID physicians who are waivered to prescribe buprenorphine are unknown.

Methods

This cross-sectional study merged data from several publicly available datasets from 1 November 2021 to 15 January 2022. Our primary outcome was the proportion of ID physicians possessing buprenorphine waivers in the United States. We identified individual- and county-level characteristics associated with buprenorphine waiver possession. We then used geospatial analysis to determine the geographic distribution of waivered ID physicians.

Results

We identified 6372 ID physicians in the United States, among whom 170 (2.7%) possessed waivers. Most ID physicians (97.3%) practiced in metropolitan counties. In our multivariable analysis, ID physicians had lower odds of having a waiver for every 10-year increase since graduating medical school (OR: .79; 95% CI: .68–.91). ID physicians practicing in counties with a higher proportion of uninsured residents had lower odds of having a waiver (OR: .75; 95% CI: .62–.90). Among counties with ≥1 ID physician (n = 729), only 11.2% had ≥1 waivered ID physician.

Conclusions

We found an extremely low prevalence and skewed geographic distribution of ID physicians with buprenorphine waivers. Our findings suggest an urgent need to increase the workforce of ID physicians waivered to prescribe buprenorphine and a call for increased integration of OUD education into ID training and continuing medical education.
Who Stands Up for the ICC? Explaining Variation in State Party Responses to US Sanctions
Authors: Broache M P , Reed Kyle
Published: November 2022

On September 2, 2020, the United States sanctioned two International Criminal Court (ICC) officials, under an executive order issued 3 months previously. In response, over two-thirds of ICC States Parties issued or joined public statements supporting the Court. Why did some ICC members condemn the sanctions or otherwise express support for the Court, while others did not? We begin by documenting variation in the type and timing of statements before proposing and testing a theory focused on the interaction between security dependence on the United States and domestic rule of law norms. We find that states more dependent on the United States for security were less likely to issue statements; furthermore, among states that issued statements, security dependence was associated with issuing weaker—and fewer—statements. Conversely, states with stronger domestic rule of law issued stronger—and more—statements, although rule of law was not significantly associated with issuing any statement.
Discrimination and Education Quality Moderate the Association of Sleep With Cognitive Function in Older Black Adults: Results From the Einstein Aging Study
Authors: Ji Linying , Zhaoyang Ruixue , Jiao June L , Schade Margeaux M , Bertisch Suzanne , Derby Carol A , Buxton Orfeu M , Gamaldo Alyssa A
Published: November 2022

Objectives

Heterogeneity among Black adults’ experiences of discrimination and education quality independently influence cognitive function and sleep, and may also influence the extent to which sleep is related to cognitive function. We investigated the effect of discrimination on the relationship between objective sleep characteristics and cognitive function in older Black adults with varying education quality.

Method

Cross-sectional analyses include Black participants in the Einstein Aging Study (N = 104, mean age = 77.2 years, 21% males). Sleep measures were calculated from wrist actigraphy (15.4 ± 1.3 days). Mean ambulatory cognitive function (i.e., spatial working memory, processing speed/visual attention, and short-term memory binding) was assessed with validated smartphone-based cognitive tests (6 daily). A modified Williams Everyday Discrimination Scale measured discriminatory experiences. Linear regression, stratified by reading literacy (an indicator of education quality), was conducted to investigate whether discrimination moderated associations between sleep and ambulatory cognitive function for individuals with varying reading literacy levels. Models controlled for age, income, sleep-disordered breathing, and sex assigned at birth.

Results

Higher reading literacy was associated with better cognitive performance. For participants with both lower reading literacy and more discriminatory experiences, longer mean sleep time was associated with slower processing speed, and lower sleep quality was associated with worse working memory. Later sleep midpoint and longer nighttime sleep were associated with worse spatial working memory for participants with low reading literacy, independent of their discriminatory experiences.

Discussion

Sociocultural factors (i.e., discrimination and education quality) can further explain the association between sleep and cognitive functioning and cognitive impairment risk among older Black adults.
Postoperative aortic injury caused by a staple line formed during wedge resection of the lung
Authors: Yamaji Masayuki , Yano Motoki , Okamaoto Sawako , Fukui Takayuki
Published: November 2022

We report a case of aortic perforation caused by the staple line formed during a wedge resection for lung cancer. Six hours after an uneventful wedge resection, sudden frank drainage of blood from the chest tube occurred. A reoperation was performed, and we found bleeding from the aorta. After suturing the bleeding spot on the aorta, we found that the stapling line of the lung rode on the aorta with longitudinal contact. We speculated that the stapling line scratched the aorta in synchrony with the patient's breathing and injured the aorta.
Surgical management of cardiac cystic echinococcosis in a paediatric patient: a case report
Authors: Biçer Mehmet , Kozan Şima , Altın Hüsnü Fırat , Aydemir Numan Ali
Published: November 2022

Cystic echinococcosis, a zoonotic parasitic disease, is endemic to many countries worldwide. This slowly progressing disease is seen rarely in the paediatric age group. In terms of cyst localization, cardiac involvement is infrequent. We report the case of a successful surgical and medical management of a paediatric hydatid disease patient with involvement of the heart.
Firearms and Clinical Practice
Authors: Pirelli Gianni , DeMarco Sarah
Published: November 2022

Firearms and Clinical Practice: A Handbook for Medical and Mental Health Professionals provides medical and mental health professionals with a practical handbook on the key connections between mental health and firearms, including but not limited to violence and suicide. This handbook will assist readers in applying firearm-related information and concepts grounded in the empirical literature and best practices in the clinical and forensic treatment and assessment arenas. As such, in addition to being an informational and educational source, its primary goal is to facilitate clinical decision-making for medical and mental health professionals practicing in a wide range of settings and contexts. Concepts are presented using a best-practices model that encourages and promotes engaging in empirically-supported clinical work. The handbook is divided into six chapters: a primer on guns; guns and the law; a review of the professional literature vis-à-vis firearms and mental health as well as emerging roles for medical and mental health professionals; therapeutic contexts; forensic mental health assessment and firearm-specific evaluations; and ethical considerations for medical and mental health professionals. The handbook also contains numerous case examples/vignettes and professional tips to consider.
Formal and Informal Social Control of Family Violence
Authors: Emery Clifton R. , Abdullah Alhassan
Published: November 2022

When intimate partner violence (IPV) is deterred or completely avoided, children benefit by living in a more stable, secure familial environment free from violence. This chapter reviews the research literature, with a particular focus on the relationship between social control and IPV, organizing the literature on both formal and informal social control into protective and punitive subtypes. Restorative justice approaches are conceptualized as situated primarily within the protective subtype, but evidence suggests that they may merit their own subtype, termed restitute social control. Finally, the chapter argues that social control of IPV and family violence must be based on an appropriate understanding of the role of family heterogeneity in the trajectory of IPV and family violence.
Physical background: X-ray generation, interaction with matter, and radiation dosimetry concepts
Authors: de Knegt Martina Chantal , Hove Jens Dahlgaard , Rossi Alexia
Published: November 2022

Cardiac CT uses X-rays to create images of the heart and coronary arteries. The main mechanisms involved in the interaction of X-rays and matter, and therefore in the creation of the CT image, are photoelectric absorption and Compton scattering. The knowledge of these mechanisms is of paramount importance as they strongly influence patient radiation dose and image quality. In dual-energy CT, the application of two X-ray beams with different energetic spectra allows for the differentiation of multiple materials. The use of X-rays has important biological implications as it may damage DNA and lead to cell death (deterministic effects) and mutation (stochastic effects). An effective radiation dose is the parameter currently employed to estimate radiation risk.
Image reconstruction, postprocessing, and fundamentals of image analysis
Authors: Khan Jamal , Moharem-Elgamal Sarah , Pugliese Francesca
Published: November 2022

Image reconstruction process produces diagnostic images from raw CT data and uses two main approaches: filtered back projection and iterative reconstruction. A CT image consists of a matrix of pixels, typically a square matrix of 512 × 512 pixels. Pixels are assigned a CT number (Hounsfield units (HUs)) that reflects the mean attenuation of the tissues included in the corresponding voxel. HUs are also affected by the energy of the X-ray beam and are normalized by the attenuation coefficient of water. The CT number scale in the image is mapped to a visual grey scale. Window settings (level/width) allow adjustment of the way CT numbers are mapped to the grey scale. Window settings determine image brightness and contrast, and are modifiable by the user. Although coronary CT angiography raw data are first reconstructed in a series of axial images, image data are isotropic and coronary artery stenosis analysis is based on multiplanar reconstructions (MPRs) and curved MPRs constructed along the vessel of interest. Maximum intensity projection and volume-rendered views display anatomical relationships between structures and are not primarily intended for fine coronary stenosis assessment.
Common CT imaging artefacts
Authors: Gaemperli Oliver
Published: November 2022

Cardiac CT image artefacts can be patient- or scan-related, and failure to recognize them can lead to misdiagnosis. Some artefacts can be avoided or reduced by appropriate patient and device selection, optimal preparation, and by adjustments in scan protocols or image reconstruction. The most common cardiac CT artefacts are blurring or discontinuity artefacts from motion (mostly cardiac); hence, the most effective measure to improve image quality is to decrease heart rate and heart rate variability. Other common artefacts include partial volume effects, beam hardening, excessive image noise, slab or banding artefacts, and low contrast enhancement.
Coronary artery calcium imaging
Authors: Willemink Martin J.
Published: November 2022

Coronary artery calcium correlates with the extent of coronary atherosclerosis and has been shown to be a strong and independent predictor of long-term cardiovascular. Coronary artery calcium estimates can be obtained from a non-contrast CT scan at low radiation exposure. The most common quantification metric is the Agatston score, but volume and mass scores can also be used. In clinical practice, coronary artery calcium scores are combined with traditional cardiovascular risk factors to improve risk stratification in asymptomatic individuals at intermediate risk. The absence of coronary artery calcium on a CT scan is associated with a very low 10-year risk. Conversely, elevated coronary artery calcium scores may identify individuals who are likely to benefit from treatment to reduce cardiovascular risk.
CT myocardial perfusion and scar imaging
Authors: Nieman Koen , Pontone Gianluca
Published: November 2022

Stress myocardial perfusion imaging by CT allows for identification of inducible myocardial ischaemia and haemodynamically significant coronary artery disease. Dynamic perfusion imaging allows for quantitative perfusion analyses but requires high-end CT technology. CT can identify acute and chronic myocardial injury based on low myocardial enhancement on CT angiograms or increased myocardial intensity on late acquired images.
Aortic valve disease
Authors: Muscogiuri Giuseppe
Published: November 2022

Aortic valve can be evaluated using coronary CT angiography (CCTA). Aortic calcification can be evaluated with non-contrast CT. In order to evaluate aortic valve morphology and function, CCTA should be acquired according to the usual protocol, including the entire cardiac cycle. The presence of aortic valve changes, as well as abnormalities of perivalvular aortic structures, can be assessed by CCTA.
Left atrium and pulmonary veins
Authors: Guglielmo Marco
Published: November 2022

Cardiac CT is a valuable tool for the detailed study of the pulmonary vein (PV), left atrium (LA), and left trial appendage (LAA) anatomy. Although transoesophageal echocardiography (TOE) remains the gold standard for ruling out LAA thrombus, cardiac CT may represent a valuable alternative to exclude LAA thrombosis when TOE is contraindicated. Preprocedural CT enables selection of the most suitable technique before an atrial fibrillation ablation procedure by providing detailed anatomical description of the PVs and LA. Furthermore, cardiac CT images can be merged with electroanatomical maps, which can be used to guide catheters during the procedure. With regard to LAA occlusion, cardiac CT is used before intervention for sizing devices and during follow-up, to identify complications such as peridevice leaks and device-related thromboses.
Dosimetry: Measuring radiation dose
Authors: Greener Tony , Byrne John
Published: November 2022

This chapter describes and explains the key concepts in determining radiation dose in tissue, which is crucial for effective radiotherapy. The key areas covered include: the variation of absorbed dose in different tissues and materials, the concepts of absorbed dose, exposure, and kerma (kinetic energy released per unit mass) and their relationship to each other. Also, the principles underlying radiation dose measurement, the methods of measurement (ionization methods, thermoluminescence, calorimetry), the importance and types of calibration standards (local and national) and factors that affect dose measurements.
X-ray beam physics
Authors: MacKay Ranald , Hounsell Alan
Published: November 2022

This chapter, ‘X-ray beam physics’, describes and discussed the physics of therapeutic X-ray beams including kilovoltage (kV) and megavoltage (MV) energy ranges. As X-ray beam is in reality a spectrum of energies, the chapter begins by explaining how the energy of a beam defined by the quality index and the different quality indices for kV and MV beams. The key clinical parameters are explored in a detailed description of beam characteristics. The physics behind the dose deposition is linked to clinically important concepts such as skin sparing explained. Other clinical characteristics such a field size, penumbra and the shape of the beam profile are defined. Finally, the chapter looks at the way the beam can be modified to improve dose deposition through the use of wedged beams.
Brachytherapy
Authors: Whitelaw Gemma , Corcoran Susan
Published: November 2022

‘Brachytherapy’ covers the use of sealed radioactive sources which are generally introduced into suitable body cavities to treat suitable cancers using automated equipment (remote afterloading) or applied directly to tumours by hand (manual afterloading). The requirements of a radioactive source to be used for brachytherapy are presented, leading into discussion on to various afterloading techniques for the treatment of prostatic and gynaecological tumours. The historically important Manchester and Paris ‘class solution’ dosimetry systems are discussed, leading into the modern practice of individualized dosimetry on a case-by-case basis. The chapter concludes with a section on quality assurance for brachytherapy and a robust presentation on the determination of reference air kerma rates for sources.
Geographic Variation in Influenza Vaccination Disparities Between Hispanic and Non-Hispanic White US Nursing Home Residents
Authors: Riester Melissa R , Roberts Anthony I , Silva Joe B B , Howe Chanelle J , Bardenheier Barbara H , van Aalst Robertus , Loiacono Matthew M , Zullo Andrew R
Published: November 2022

Background

Disparities in influenza vaccination exist between Hispanic and non-Hispanic White US nursing home (NH) residents, but the geographic areas with the largest disparities remain unknown. We examined how these racial/ethnic disparities differ across states and hospital referral regions (HRRs).

Methods

This retrospective cohort study included >14 million short-stay and long-stay US NH resident-seasons over 7 influenza seasons from October 1, 2011, to March 31, 2018, where residents could contribute to 1 or more seasons. Residents were aged ≥65 years and enrolled in Medicare fee-for-service. We used the Medicare Beneficiary Summary File to ascertain race/ethnicity and Minimum Data Set assessments for influenza vaccination. We calculated age- and sex-standardized percentage point (pp) differences in the proportions vaccinated between non-Hispanic White and Hispanic (any race) resident-seasons. Positive pp differences were considered disparities, where the proportion of non-Hispanic White residents vaccinated was greater than the proportion of Hispanic residents vaccinated. States and HRRs with ≥100 resident-seasons per age–sex stratum per racial/ethnic group were included in analyses.

Results

Among 7 442 241 short-stay resident-seasons (94.1% non-Hispanic White, 5.9% Hispanic), the median standardized disparities in influenza vaccination were 4.3 pp (minimum, maximum: 0.3, 19.2; n = 22 states) and 2.8 pp (minimum, maximum: −3.6, 10.3; n = 49 HRRs). Among 6 758 616 long-stay resident-seasons (93.7% non-Hispanic White, 6.5% Hispanic), the median standardized differences were −0.1 pp (minimum, maximum: −4.1, 11.4; n = 18 states) and −1.8 pp (minimum, maximum: −6.5, 7.6; n = 34 HRRs).

Conclusions

Wide geographic variation in influenza vaccination disparities existed across US states and HRRs. Localized interventions targeted toward areas with high disparities may be a more effective strategy to promote health equity than one-size-fits-all national interventions.
Impact of the Coronavirus Disease 2019 Pandemic on Antiretroviral Therapy Initiation and Care Delivery for People With Newly Diagnosed HIV in an Integrated Healthcare System
Authors: Mohr Kurtis B , Lee-Rodriguez Christian , Samiezade-Yazd Zahra , Lam Jennifer O , Imp Brandon M , Luu Mitchell N
Published: November 2022

The coronavirus disease 2019 (COVID-19) pandemic disrupted health systems. For patients newly diagnosed with human immunodeficiency virus, starting immediate antiretroviral therapy (ART) is recommended. For periods before and during the COVID-19 pandemic, Kaiser Permanente Northern California found similar rates of rapid ART initiation and time to viral suppression, concurrent with an increase in telemedicine.
The uprise of gun violence in the United States: consequences of a dual pandemic
Authors: Schellenberg Morgan , Walters Andrew
Published: November 2022

Purpose of review

The global coronavirus disease 2019 (COVID-19) viral outbreak and the rise of the anti-Black racism movement have produced a dual pandemic over the past few years, which has been associated with a dramatic rise in gun violence across the United States. This comprehensive review was performed to examine the current levels of gun violence in the context of these dual pandemics, delineate factors which have synergistically produced this surge in interpersonal violence, and propose future directions.

Recent findings

Dual pandemics have mutually contributed to a worsening in many social determinants of health and thereby have had a particularly dramatic impact on many of our most vulnerable patients, including patients of minority races and ethnicities, in terms of interpersonal violence. Firearm injuries are at their highest rate in decades. The challenges in the trauma care of these patients have been compounded by staffing and resource shortages related to the COVID-19 pandemic and attrition of medical workers related to burnout.

Consequences of the COVID-19 pandemic and the anti-Black racism movement have produced a social environment in the United States in recent years where interpersonal violence, especially firearm injuries, have surged. Particularly, during a time of challenged patient care delivery, the medical system struggles to support the increase in trauma volume. A broad approach to improving social determinants of health should be pursued in order to decrease the risk of gun violence from the recent near-historical high levels.
Thoracic irradiation as consolidation therapy in patients with extensive-stage small cell lung cancer
Authors: Berta Judit , Rózsás Anita , Megyesfalvi Zsolt , Ostoros Gyula , Döme Balázs
Published: November 2022

Purpose of review

Small cell lung cancer (SCLC) is marked by an exceptionally high proliferative rate and poor prognosis. Given its high propensity to metastasize, nearly two-thirds of SCLC patients are diagnosed with extensive-stage (ES) disease when surgery is not a treatment option anymore. Over several decades, only minimal changes have been made in the therapeutic armamentarium of ES-SCLC. Recently, however, several new therapeutic avenues were defined, thus renewing the hope for patients with this recalcitrant cancer. Here, we present an overview of the most current therapeutic advances in ES-SCLC focusing in particular on consolidative thoracic radiation therapy (cTRT) and chemo-immunotherapy.

Recent findings

The incorporation of immunotherapy in the standard-of-care of ES-SCLC patients and the resulting outcomes are both a remarkable hallmark of progress and a disappointment. Indeed, chemo-immunotherapy with or without cTRT and prophylactic cranial irradiation contributes to longer survival outcomes with minimal toxicity rates in well selected and properly monitored patients. Nevertheless, the gain in overall survival is still modest relative to that seen in many other solid tumors.

Despite the encouraging results, further clinical trials are needed to determine the efficacy and safety of these therapeutic approaches, and moreover, to identify new predictive biomarkers of response.
Role of Surgical Pathologist for Detection of Predictive Immuno-oncological Factors in Breast Cancer
Authors: Berner Mandy , Hartmann Arndt , Erber Ramona
Published: November 2022

Immune checkpoint inhibitors (ICIs) have changed therapy strategies in breast cancer (BC) patients suffering from triple-negative breast cancer (TNBC). For example, in Europe the anti-programmed cell death 1 ligand 1 (PD-L1) ICI Azetolizumab is approved for adult patients with locally advanced or metastasized TNBC (mTNBC), depending on the immunohistochemical (IHC) PD-L1 expression of immune cells in the tumor area [immune cell (IC) score ≥1%); the anti-programmed cell death 1 (PD-1) ICI pembrolizumab is approved for mTNBC if PD-L1 Combined Positive Score (CPS), that is PD-L1 expression on tumor and/or immune cells, is ≥10. For early TNBC, in contrast, neoadjuvant use of pembrolizumab is approved in the United States and Europe independent from PD-L1 IHC expression. The determination of PD-L1 expression in tumor tissue to predict response to ICI therapy requires sensitive immunostaining with appropriate primary antibodies and staining protocols and a standardized and meticulous assessment of PD-L1 IHC stained breast cancer tissue slides. For the selection of the test material and continuous quality control of the dyeing, high standards must be applied. The evaluation is carried out according to various evaluation algorithms (scores). Here, the role of PD-L1 in BC and the currently most relevant PD-L1 assays and scores for TNBC will be explained. Furthermore, other tissue-based biomarkers potentially predictive for ICI therapy response in BC, for example, tumor mutational burden (TMB), will be presented in this review.
Neuron Navigator 1Regulates Learning, Memory, and the Response to Multiple Potentially Addictive Drugs
Authors: Bagley Jared R. , Tan Yalun , Zhu Wan , Cheng Zhuanfen , Takeda Saori , Fang Zhouqing , Arslan Ahmed , Wang Meiyue , Guan Yuan , Jiang Lihua , Jian Ruiqi , Gu Feng , Parada Isabel , Prince David , Jentsch J. David , Peltz Gary
Published: November 2022

Genetic variation accounts for much of the risk for developing a substance use disorder (SUD). Inbred mouse strains exhibit substantial and heritable differences in the extent of voluntary cocaine intravenous self-administration (IVSA). Computational genetic analysis of IVSA data obtained from an inbred strain panel identifiedNav1,a member of the neuron navigator family that regulates dendrite formation and axonal guidance, as a candidate gene. To test this hypothesis, we generated and characterizedNav1knockout (KO) mice.Nav1KO mice exhibited increased cocaine intake during IVSA testing. Surprisingly,Nav1KO mice also displayed a reduced susceptibility to become opioid dependent or develop opioid-induced hyperalgesia after chronic morphine administration, and had impaired spatial learning/memory. Immunohistochemistry and electrophysiology studies revealed that inhibitory synapse density in the cortex ofNav1KO mice was reduced, and excitatory synaptic transmission was increased in theNav1KO cortex and hippocampus. Transcriptomic analysis revealed thatNav1KO mice had a marked increase in excitatory neurons in a deep cortical layer. Collectively, our results indicate thatNav1regulates learning, memory, and the response to multiple addictive drugs, and that changes in the excitatory and inhibitory synaptic balance in the cortex and hippocampus could possibly mediate these phenotypic effects.
The need for ecologically realistic studies on the health effects of microplastics
Authors: Mills C Lauren , Savanagouder Joy , de Almeida Monteiro Melo Ferraz Marcia , Noonan Michael J
Published: November 2022

Plastic pollution is now so widespread that microplastics are consistently detected in every biological sample surveyed for their presence. Despite their pervasiveness, very little is known about the effects of microplastics on the health of terrestrial species. While emerging studies are showing that microplastics represent a potentially serious threat to animal health, data have been limited toin vivostudies on laboratory rodents that were force fed plastics. The extent to which these studies are representative of the conditions that animals and humans might actually experience in the real world is largely unknown. Here, we review the peer-reviewed literature in order to understand how the concentrations and types of microplastics being administered in lab studies compare to those found in terrestrial soils. We found that lab studies have heretofore fed rodents microplastics at concentrations that were hundreds of thousands of times greater than they would be exposed to in nature. Furthermore, health effects have been studied for only 10% of the microplastic polymers that are known to occur in soils. The plastic pollution crisis is arguably one of the most pressing ecological and public health issues of our time, yet existing lab-based research on the health effects of terrestrial microplastics does not reflect the conditions that free-ranging animals are actually experiencing. Going forward, performing more true-to-life research will be of the utmost importance to understand the impacts of microplastics and maintain the public’s faith in the scientific process.
The Cation/H+exchanger OsCAX2 is involved in cadmium tolerance and accumulation through vacuolar sequestration in rice
Authors: Zou Wenli , Zhan Junhui , Meng Lijun , Chen Yuetong , Chen Dandan , Zhang Mingpei , He Haohua , Chen Jingguang , Ye Guoyou
Published: November 2022

Excessive cadmium (Cd) in rice grains is a serious food safety problem. The development of Cd-safe varieties requires the identification of germplasms and genes with major effect on Cd accumulation but without negative effects on other important traits. Here, we reported that OsCAX2, a member of the rice Cation/H+exchanger (CAX) family, is an important Cd transporter.OsCAX2encodes a tonoplast-localized protein and is strongly upregulated by Cd, mainly expresses in root exodermis, parenchyma in cortex, endodermis and stele cells. Depletion ofOsCAX2resulted in enhanced Cd sensitivity and root-to-shoot translocation in rice, while overexpression ofOsCAX2significantly increased Cd tolerance and reduced Cd transport by promoting root Cd influx and vacuolar storage, which ultimately reduced Cd transport via xylem.OsCAX2also had significant effects on tissues/organs distribution of Cd but had no effects on grain yield and agronomic traits. Importantly, theOsCAX2overexpressing lines had more than 70% lower grain Cd accumulation, increased iron (Fe), zinc (Zn) and manganese (Mn) and reduced copper (Cu) accumulation. Therefore,OsCAX2is an ideal gene for developing Cd-safe rice varieties via transgenic approach.
MerCat2: a versatilek-mer counter and diversity estimator for database-independent property analysis obtained from omics data
Authors: Figueroa Jose L. , Panyala Ajay , Colby Sean , Friesen Maren , Tiemann Lisa , White Richard Allen
Published: November 2022

MerCat2 (“Mer-Catenate2”) is a versatile, parallel, scalable and modular property software package for robustly analyzing features in omics data. Using massively parallel sequencing raw reads, assembled contigs, and protein sequences from any platform as input, MerCat2 performsk-mer counting of any lengthk, resulting in feature abundance counts tables, quality control reports, protein feature metrics, ecological diversity metrics, and graphical representation (i.e., PCA). MerCat2 allows for direct analysis of data properties in a database-independent manner that initializes all data, which other profilers and assembly-based methods cannot perform. MerCat2 represents an integrated tool to illuminate omics data within a sample for rapid cross-examination and comparisons.

Availability and implementation

MerCat2 is written in Python and distributed under a BSD-3 license. The source code of MerCat2 is freely available athttps://github.com/raw-lab/mercat2. MerCat2 is compatible with Python 3 on Mac OS X and Linux. MerCat2 can also be easily installed using bioconda: conda install MerCat2.

Contact

Richard Allen White III, UNC Charlotte,rwhit101@uncc.edu

Supplementary information

Supplementary data are available online.
Behavioral signatures of face perception emerge in deep neural networks optimized for face recognition
Authors: Dobs Katharina , Yuan Joanne , Martinez Julio , Kanwisher Nancy
Published: November 2022

Human face recognition is highly accurate, and exhibits a number of distinctive and well documented behavioral “signatures” such as the use of a characteristic representational space, the disproportionate performance cost when stimuli are presented upside down, and the drop in accuracy for faces from races the participant is less familiar with. These and other phenomena have long been taken as evidence that face recognition is “special”. But why does human face perception exhibit these properties in the first place? Here we use deep convolutional neural networks (CNNs) to test the hypothesis that all of these signatures of human face perception result from optimization for the task of face recognition. Indeed, as predicted by this hypothesis, these phenomena are all found in CNNs trained on face recognition, but not in CNNs trained on object recognition, even when additionally trained to detect faces while matching the amount of face experience. To test whether these signatures are in principle specific to faces, we optimized a CNN on car discrimination and tested it on upright and inverted car images. As for face perception, the car-trained network showed a drop in performance for inverted versus upright cars. Similarly, CNNs trained only on inverted faces produce an inverted inversion effect. These findings show that the behavioral signatures of human face perception reflect and are well explained as the result of optimization for the task of face recognition, and that the nature of the computations underlying this task may not be so “special” after all.

Significance Statement

For decades, cognitive scientists have collected and characterized behavioral signatures of face recognition. Here we move beyond the mere curation of behavioral phenomena to asking why the human face system works the way it does. We find that many classic signatures of human face perception emerge spontaneously in CNNs trained on face discrimination, but not in CNNs trained on object classification (or on both object classification and face detection), suggesting that these long-documented properties of the human face perception system reflect optimizations for face recognition per se, not by-products of a generic visual categorization system. This work further illustrates how CNN models can be synergistically linked to classic behavioral findings in vision research, thereby providing psychological insights into human perception.
Mapping the content of comments on bioRxiv and medRxiv preprints
Authors: Carneiro Clarissa F. D. , Costa Gabriel , Neves Kleber , Abreu Mariana B. , Tan Pedro B. , Rayêe Danielle , Boos Flávia , Andrejew Roberta , Lubiana Tiago , Malički Mario , Amaral Olavo B.
Published: November 2022

Introduction

Preprints have been increasingly used in biomedical sciences, providing the opportunity for research to be publicly assessed before journal publication. With the increase in attention over preprints during the COVID-19 pandemic, we decided to assess the content of comments left on preprint platforms.

Methods

Preprints posted on bioRxiv and medRxiv in 2020 were accessed through each platform’s API, and a random sample of preprints that had received between 1 and 20 comments was analyzed. Comments were evaluated in triplicate by independent evaluators using an instrument that assessed their features and general content.

Results

7.3% of preprints received at least 1 comment during a mean follow-up of 7.5 months. Analyzed comments had a median size of 43 words. Criticisms, corrections or suggestions were the most prevalent type of content, followed by compliments or positive appraisals and questions. Most critical comments regarded interpretation, data collection and methodological design, while compliments were usually about relevance and implications.

Conclusions

Only a small percentage of preprints posted in 2020 in bioRxiv and medRxiv received comments in these platforms. When present, however, these comments address content that is similar to that analyzed by traditional peer review. A more precise taxonomy of peer review functions would be desirable to describe whether post-publication peer review fulfills these roles.
Cooperative breeding in a plural breeder: the vulturine guineafowl (Acryllium vulturinum)
Authors: Nyaguthii Brendah , Dehnen Tobit , Klarevas-Irby James A. , Papageorgiou Danai , Kosgey Joseph , Farine Damien R.
Published: November 2022

Cooperative breeding is widely reported across the animal kingdom. In birds, it is hypothesised to be most common in altricial species (where chicks are dependent on parental care in the nest after hatching), with few described cases in precocial species (where chicks are more independent immediately after hatching). However, cooperative breeding may also be more difficult to detect in precocial species and therefore has been overlooked. In this study, we investigate whether vulturine guineafowl (Acryllium vulturinum)—which have precocial young—breed cooperatively and, if so, how care is distributed among group members. Using data collected from colour-banded individuals in one social group of vulturine guineafowl over three different breeding seasons, we found that multiple females can attempt to reproduce in the same breeding season. Broods had close adult associates, and most of these associates exhibited four distinct cooperative breeding behaviours: babysitting, within-group chick guarding, covering the chicks under the wings and calling the chicks to food. Further, we found that offspring care is significantly male-biased, that non-mother individuals provided most of the care each brood received, that breeding females differed in how much help they received, and that carers pay a foraging cost when providing care. Our results confirm that vulturine guineafowl are cooperative breeders, which they combine with an unusual plural-breeding social system. Our study also adds to growing evidence that cooperative breeding may be more widespread among species with precocial young than previously thought, thereby providing a counterpoint to the altriciality-cooperative breeding hypothesis.
Physiological adaptation of sulfate reducing bacteria in syntrophic partnership with anaerobic methanotrophic archaea
Authors: Murali Ranjani , Yu Hang , Speth Daan R. , Wu Fabai , Metcalfe Kyle S. , Crémière Antoine , Laso-Pèrez Rafael , Malmstrom Rex R. , Goudeau Danielle , Woyke Tanja , Hatzenpichler Roland , Chadwick Grayson L. , Orphan Victoria J.
Published: November 2022

Sulfate-coupled anaerobic oxidation of methane (AOM) is performed by multicellular consortia of anaerobic methanotrophic archaea (ANME) in obligate syntrophic partnership with sulfate-reducing bacteria (SRB). Diverse ANME and SRB clades co-associate but the physiological basis for their adaptation and diversification is not well understood. In this work, we explore the metabolic adaptation of four syntrophic SRB clades (HotSeep-1, Seep-SRB2, Seep-SRB1a and Seep-SRB1g) from a phylogenomics perspective, tracing the evolution of conserved proteins in the syntrophic SRB clades, and comparing the genomes of syntrophic SRB to their nearest evolutionary neighbors in the phylum Desulfobacterota. We note several examples of gain, loss or biochemical adaptation of proteins within pathways involved in extracellular electron transfer, electron transport chain, nutrient sharing, biofilm formation and cell adhesion. We demonstrate that the metabolic adaptations in each of these syntrophic clades are unique, suggesting that they have independently evolved, converging to a syntrophic partnership with ANME. Within the clades we also investigated the specialization of different syntrophic SRB species to partnerships with different ANME clades, using metagenomic sequences obtained from ANME and SRB partners in individual consortia after fluorescent-sorting of cell aggregates from anaerobic sediments. In one instance of metabolic adaptation to different partnerships, we show that Seep-SRB1a partners of ANME-2c appear to lack nutritional auxotrophies, while the related Seep-SRB1a partners of a different methanotrophic archaeal lineage, ANME-2a, are missing the cobalamin synthesis pathway, suggesting that the Seep-SRB1a partners of ANME-2a may have a nutritional dependence on its partner. Together, our paired genomic analysis of AOM consortia highlights the specific adaptation and diversification of syntrophic SRB clades linked to their associated ANME lineages.