bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexual-biased necroinflammation is revealed as a predictor of bevacizumab benefit in glioblastoma
Authors: Hiller-Vallina Sara , Mondejar-Ruescas Lucia , Caamaño-Moreno Marta , Cómitre-Mariano Blanca , Alcivar-López Denisse , Sepulveda Juan M , Hernández-Laín Aurelio , Pérez-Núñez Ángel , Segura-Collar Berta , Gargini Ricardo
Published: February 2024

Background

Glioblastoma (GBM) is a highly malignant brain tumor that affects men more often than women. In addition, the former shows a poorer survival prognosis. To date, the reason for this sex-specific aggressiveness remains unclear. Therefore, the aim of this study is to investigate tumor processes that explain these sex differences.

Methods

This was a retrospective study of GBM patients which was stratified according to sex. A cohort with 73 tumors was analyzed with immunohistochemistry, RNA-seq and RT–qPCR to characterize differences in vascular and immunological profiles. Transcriptomic profiling, gene set enrichment analysis, and pathway enrichment analysis were used for discovering molecular pathways predominant in each group. We further investigated the therapeutic effect of bevacizumab (vascular endothelial growth factor A (VEGFA) blocking antibody) in a retrospective GBM cohort (36 tumors) based on sex differences.

Results

We found that under hypoxic tumor conditions, 2 distinct tumor immuno-angiogenic ecosystems develop linked to sex differences and ESR1 expression is generated. One of these subgroups, which includes male patients with low ESR1 expression, is characterized by vascular fragility associated with the appearance of regions of necrosis and high inflammation (called necroinflamed tumors). This male-specific tumor subtype shows high inflammation related to myeloid-derived suppressor cells infiltration. Using this stratification, we identified a possible group of patients who could respond to bevacizumab (BVZ) and revealed a genetic signature that may find clinical applications as a predictor of those who may benefit most from this treatment.

Conclusions

This study provides a stratification based on the sexual differences in GBM, which associates the poor prognosis with the presence of immunosuppressive myeloid cells in the necrotic areas. This new stratification could change the current prognosis of GBM and identifies those who respond to BVZ treatment.
High-quality genome assembly enables prediction of allele-specific gene expression in hybrid poplar
Authors: Shi Tian-Le , Jia Kai-Hua , Bao Yu-Tao , Nie Shuai , Tian Xue-Chan , Yan Xue-Mei , Chen Zhao-Yang , Li Zhi-Chao , Zhao Shi-Wei , Ma Hai-Yao , Zhao Ye , Li Xiang , Zhang Ren-Gang , Guo Jing , Zhao Wei , El-Kassaby Yousry Aly , Müller Niels , Van de Peer Yves , Wang Xiao-Ru , Street Nathaniel Robert , Porth Ilga , An Xinmin , Mao Jian-Feng
Published: February 2024

Poplar (Populus) is a well-established model system for tree genomics and molecular breeding, and hybrid poplar is widely used in forest plantations. However, distinguishing its diploid homologous chromosomes is difficult, complicating advanced functional studies on specific alleles. In this study, we applied a trio-binning design and PacBio high-fidelity long-read sequencing to obtain haplotype-phased telomere-to-telomere genome assemblies for the 2 parents of the well-studied F1 hybrid “84K” (Populus alba × Populus tremula var. glandulosa). Almost all chromosomes, including the telomeres and centromeres, were completely assembled for each haplotype subgenome apart from 2 small gaps on one chromosome. By incorporating information from these haplotype assemblies and extensive RNA-seq data, we analyzed gene expression patterns between the 2 subgenomes and alleles. Transcription bias at the subgenome level was not uncovered, but extensive-expression differences were detected between alleles. We developed machine-learning (ML) models to predict allele-specific expression (ASE) with high accuracy and identified underlying genome features most highly influencing ASE. One of our models with 15 predictor variables achieved 77% accuracy on the training set and 74% accuracy on the testing set. ML models identified gene body CHG methylation, sequence divergence, and transposon occupancy both upstream and downstream of alleles as important factors for ASE. Our haplotype-phased genome assemblies and ML strategy highlight an avenue for functional studies in Populus and provide additional tools for studying ASE and heterosis in hybrids.
Genetic effects of inflammatory cytokines on coronary artery disease and myocardial infarction and the mediating roles of lipid traits
Authors: Liu Junsong , Ying Jiajun , Hu Teng
Published: February 2024

Background

Chronic inflammation has been connected by epidemiological evidence to coronary artery disease (CAD) along with myocardial infarction (MI). Nevertheless, it is still unclear whether reverse causality or confounders account for these connections. Our objectives are to examine the causality between inflammatory cytokines and CAD/MI as well as the potential mediating influence of lipid characteristics.

Methods

We acquired instrumental variables through genome-wide association studies meta-analyses of 41 inflammatory cytokines (8293 individuals). Genetic associations with CAD (122 733 cases and 424 528 controls), MI (~61 505 cases and 577 716 controls) and five candidate lipid mediators were obtained from the corresponding genome-wide association studies. A two-step, two-sample Mendelian randomization analysis was applied, followed with comprehensive sensitivity analyses.

Results

Genetically determined growth regulated oncogene-α was causally linked to a decreased incidence of CAD [odds ratio (OR), 0.97; 95% confidence interval (CI), 0.95-0.99; P = .007] and MI (OR, 0.95; 95% CI, 0.92-0.98; P = .002). There is suggestive evidence indicating a causal impact of macrophage inflammatory protein-1β upon CAD (OR, 1.04; 95% CI, 1.01–1.07; P = .010) and MI (OR, 1.07; 95% CI, 1.02–1.11; P = .002). Furthermore, we discovered suggestive causal connections between tumor necrosis factor-related apoptosis-inducing ligand and CAD (OR, 0.97; 95% CI, 0.95–1.00; P = .020). Two-step Mendelian randomization analysis revealed that triglycerides partially mediate the effect of growth regulated oncogene-α on CAD (proportion-mediated: 13.28%) and MI (8.05%).

Conclusions

We provided novel genetic evidence supporting the causality of inflammatory cytokines on CAD/MI and elucidate the mediating effect of triglycerides in the causal pathways linking inflammatory cytokines and CAD/MI.
Application of the Staged Approach for Rehabilitation Classification System and Associated Improvements in Patient-Reported Outcomes Following Rehabilitation for Shoulder Pain
Authors: Podschun Laura , Hill Cheryl , Kolber Morey J , McClure Philip
Published: February 2024

Objective

The Staged Approach for Rehabilitation Classification for the Shoulder (STAR-Shoulder) has been proposed as a model to guide management and improve outcomes for patients with shoulder pain; however, the effect of its utilization on patient outcomes has not been established. Therefore, the primary purpose of this study was to determine whether patient outcomes were improved if care was matched to the STAR-Shoulder system compared with unmatched care.

Methods

Collected and reviewed demographic, examination, and intervention data for all patients receiving physical therapist treatment for shoulder pain during a 1-year period within a single health care system. Outcome variables included the numeric pain rating scale, the Quick Disabilities of the Arm, Shoulder and Hand Questionnaire (QuickDASH), and the number of visits. Clinical records from patients receiving care at the discretion of the therapist were systematically audited to determine whether care provided was considered matched or unmatched.

Results

A total of 692 patient records were examined. The interrater reliability of classifying care as matched or unmatched was substantial (κ = 0.6; 95% CI = 0.4 to 0.9), with 82% agreement. Changes in patient outcome scores were significantly better for those patients whose care matched the STAR-Shoulder system for pain changes (mean difference = −1.2; 95% CI = 0.8 to 1.6; effect size [d] = 0.5) and QuickDASH score (mean difference = 12.7; 95% CI = 9.9 to 15.5; d = 0.7). No difference was noted for number of visits.

Conclusion

The STAR-Shoulder system appears to be a meaningful way to classify patients and guide intervention to improve patient outcomes.

Impact

Application of the STAR-Shoulder system to help align physical therapist interventions more closely with tissue irritability and physical impairments appears to improve patient outcomes. These findings support this model as a promising approach to advance evidence-based practice for shoulder pain.
The lived experience of food insecurity among adults with obesity: a quantitative and qualitative systematic review
Authors: Briggs Rebecca , Rowden Hope , Lagojda Lukasz , Robbins Timothy , Randeva Harpal S
Published: February 2024

Background

Food insecurity and obesity are increasing both globally and in the UK. In this review we systematically assess the lived experiences of people with obesity who are food insecure and often turn to food banks.

Methods

We systematically searched electronic databases from January 2007 until October 2022. Data from eligible studies were extracted and the studies assessed for quality. Thematic analysis and narrative synthesis approach was used to analyse the extracted data.

Results

Six themes were identified among 25 included studies, including: the financial cost of food; psychological aspects related to food insecurity; geographical access and the food environment; food practices in the home; experience of food assistance; and parental-child relationships. The cost of healthy food and psychological factors were identified as key driving factors of the relationship between food insecurity and obesity. Psychological factors such as depression, low self-esteem and stress played an important part in the lived experience of people with obesity and food insecurity.

Conclusion

The food environment provides context in which food decisions are made, therefore, systems change is necessary to ensure families can afford the food that enables a healthy diet. For clinicians, identification, and attention to the impact of food insecurity on people with obesity are important.
Surviving Competition: Neighbourhood Shops versus Convenience Chains
Authors: Talamas Marcos Miguel Ángel
Published: February 2024

Hundreds of millions of microenterprises in emerging economies face increased competition from the entry and expansion of large firms that offer similar products. This paper examines the impacts of the opening of chain-run convenience stores on one of the world’s most ubiquitous microenterprises: owner-operated shops. To address endogeneity in time and location of chains’ opening, I pair two-way fixed effects with a novel instrument that shifts the profitability of chains but not of shops at the neighbourhood level. Expanding the number of chain outlets from zero to the neighbourhood average of 6.7 stores reduces the number of shops by 15%, a decline driven not by increased shop exits but by decreased shop entries. Shops retain their sales of fresh products and keep 96% of their customers, but customers visit shops less frequently and spend less on packaged goods. Surviving shops leverage competitive advantages stemming from being owner operated, such as lower agency costs, cultivating relationships with neighbours, and offering customers informal credit. The welfare gains of convenience chains replacing shops increase with household income; the poorest households experience a welfare loss.
Policy Responses To Fake News On Social Media Platforms: A Law And Economics Analysis
Authors: Kaushik Devansh
Published: February 2024

Fake News is one of the major techno-policy challenges faced by modern societies. As popular discourse shifts to social media platforms, Fake News on the internet has increased drastically, generating significant costs for society. Consequently, there is a regulatory movement across the globe to mitigate fake news on these platforms. A law and economics analysis offers valuable insights towards devising an appropriate regulatory approach to tackling this issue.

In economic terms, Fake News can be conceptualized as a negative externality, while Fact-Checking and Content Moderation Services may be defined as public goods. There exists a misplaced individual incentive to create fake news on social media platforms. A clear case of market failure and thus a need for state intervention can be made out.

While direct state regulation of platforms is the preferred approach by regulators for mitigating fake news, this paper cautions against over-reliance on such a ‘negative state’ regime, due to censorship risks and enforcement costs. This paper recommends adoption of a multi-pronged strategy, including a statutory Pigouvian tax to internalize social costs of fake news on social media platforms within the market, by channelling resources towards promoting positive state measures to mitigate the broader effects of fake news on these platforms. This paper’s analysis is largely located in the Indian context, with references to other jurisdictions.
Modification of vertebral regions explains heart position in arboreal colubrids (Serpentes: Colubridae)
Authors: Nash-Hahn Tamika , Stepanova Natasha , Davis Rabosky Alison R , Sherratt Emma
Published: February 2024

Recent research into the snake vertebral column has highlighted the importance of considering regionalization and its implications for the life history of snakes. Our research delves into the distinctions in vertebral column morphology and regionalization within the snake family Colubridae, comparing arboreal and terrestrial species. Our results provide significant support for dissociation between two pre-cloacal regions: the ‘pre-atrial’ (anterior to heart) and the ‘post-atrial’ (posterior to heart). Furthermore, the two ecological groups display distinct proportional compositions between the two pre-cloacal regions and the one post-cloacal region (caudal); arboreal species tend to possess a higher proportion of caudal vertebrae, whereas terrestrial species exhibit a higher proportion of post-atrial vertebrae. Our study reveals that the axial morphology of arboreal species is distinct from that of terrestrial species; however, this was not attributable to a convergent evolution process. By estimating the evolutionary history of vertebral number in each region between the ecological groups, we find each region has a unique pattern, further highlighting evolutionary disassociation between the regions. This study adds to the growing evidence on regionalization of the pre-cloacal snake vertebral column and underscores the importance in continuing to develop our understanding of snake evolution.
It’s a Trap! Part I: Exploring the Applications of Rotating-Arm Impaction Samplers in Plant Pathology
Authors: Check Jill C. , Harkness Rebecca J. , Heger Lexi , Sakalidis Monique L. , Chilvers Martin I. , Mahaffee Walter F. , Miles Timothy D.
Published: February 2024

Although improved knowledge on the movement of airborne plant pathogens is likely to benefit plant health management, generating this knowledge is often far more complicated than anticipated. This complexity is driven by the dynamic nature of environmental variables, diversity among pathosystems that are targeted, and the unique needs of each research group. When using a rotating-arm impaction sampler, particle collection is dependent on the pathogen, environment, research objectives, and limitations (monetary, environmental, or labor). Consequently, no design will result in 100% collection efficiency. Fortunately, it is likely that multiple approaches can succeed despite these constraints. Choices made during design and implementation of samplers can influence the results, and recognizing this influence is crucial for researchers. This article is for beginners in the art and science of using rotating-arm impaction samplers; it provides a foundation for designing a project, from planning the experiment to processing samples. We present a relatively nontechnical discussion of the factors influencing pathogen dispersal and how placement of the rotating-arm air samplers alters propagule capture. We include a discussion of applications of rotating-arm air samplers to demonstrate their versatility and potential in plant pathology research as well as their limitations.
Application of the 4-Element Movement Model to Cardiovascular and Pulmonary Physical Therapy Practice
Authors: Bills Sara , Skrzat Julie , Tevald Michael A.
Published: February 2024

The 4-Element Movement Model (4EMM) has been proposed as framework to guide clinical decision making in the physical therapy management of individuals with movement disorders. The model is centered on the primary elements of movement, including motion, force, control, and energy. Clinical application of the model begins with the selection of a movement task, followed by systematic observation of the performance of the task, including control, amount, speed, symmetry, and symptoms provoked during the movement. Testable hypotheses about the impairments contributing to movement problems are then generated, which inform the examination and intervention. A major advantage of the model is its broad applicability to a range of patient populations and settings. In this clinical perspective, we describe the application of the 4EMM to patients with cardiac, vascular, and pulmonary impairments.
Acute Myocardial Infarction in Pregnancy
Authors: Kim Jitae A. , Kim Sophie Y. , Virk Hafeez Ul Hassan , Alam Mahboob , Sharma Samin , Johnson Mark R. , Krittanawong Chayakrit
Published: February 2024

Pregnancy-associated myocardial infarction is an overall uncommon event, but can be associated with significant maternal and fetal morbidity and mortality. In contrast to myocardial infarction in the general nonpregnant population, the mechanism of pregnancy-associated myocardial infarction is most commonly due to nonatherosclerotic mechanisms such as coronary dissection, vasospasm, or thromboembolism. The diagnosis of pregnancy-associated myocardial infarction can be challenging, requiring a high index of suspicion for prompt recognition and management. Furthermore, the management of pregnancy-associated myocardial infarction can be complex due to maternal and fetal considerations and may vary based on the specific underlying mechanism of the myocardial infarction. This review aims to review the recent literature on pregnancy-associated myocardial infarction and summarize the epidemiology, mechanisms, diagnosis, and treatment strategies for this uncommon entity.
A Systematic Evaluation of the Quality of Health Information on Cleft Lip and Palate in the Arabic Language
Authors: Al Qurashi Abdullah A. , Shah Mardan Qutaiba N.M. , Mawad Tala N. , Alsubhi Razan Omar , Bokhari Abdulah , Daghistani Ghadeer , Abualjamal Rena Y. , Alharbi Amal Mohammed , Al Qarni Mohammed D. , Alhuzali Abdullah , Mrad Mohamed Amir
Published: February 2024

Background:

The internet serves as a vital health information resource, yet the quality of data on specific health conditions, especially in Arabic, is often overlooked. This research assesses the quality of Arabic online information about cleft lip and palate (CLP) and proposes avenues for enhancement.

Methods:

From July to August 2022, a systematic evaluation of Arabic articles on CLP was performed using the DISCERN tool for quality assessment. Searches on Google and Bing resulted in 119 articles that met the study’s criteria.

Results:

The quality of available Arabic information on CLP displayed substantial gaps. Commercial sources dominated (49.6%), followed by private (32.8%) and nonprofit entities (17.6%). The average DISCERN score was 2.26 of 5 (SD = 1.06), indicating the need for enhanced content, particularly concerning treatment risks.

Conclusions:

The study underscores the subpar quality of Arabic CLP information online, which might mislead patients and impede access to accurate advice. Nonprofit organizations should bolster their online footprint, offering refined health content. A deep dive into DISCERN scores reveals pinpointed improvement areas. Clinicians should direct patients and their families to reliable information sources. Addressing these gaps promises improved CLP knowledge in Arabic, fostering superior patient education and outcomes for those with this condition.
Mining Injuries 2012–2019
Authors: Heberger John R. , Wurzelbacher Steven J.
Published: February 2024

Objective

This study summarized the frequency and cost of mining-related injuries.

Methods

Mining-related workers’ compensation (WC) claims data from 35 states were summarized to report counts, claim rates, and costs for 2012–2019. These data were compared with Mine Safety and Health Administration injury and employment data for the same period.

Results

Despite system differences, both WC and Mine Safety and Health Administration counts and rates declined over time and injury patterns were similar. Total WC costs were approximately $2.325B. Medical-only claims represented 59.4% of the claims by count, but only 3.3% of costs. Lost-time nonfatal claims represented 40.2% of the claims by count, but 90.2% of costs. Claims frequency and costs varied greatly by injury event/exposure, part of body, and nature.

Conclusions

Injury frequency has declined but costs remain high. The most costly and disabling cases were identified.
More than Just Workload—Personnel’s Perspective on Workload at the Royal Netherlands Marechaussee
Authors: Stegerhoek Pablo M. , van der Zande Jesse , IJzerman Herman , Verhagen Evert A. L. M. , Kuijer P. Paul F. M. , Bolling Caroline
Published: February 2024

Objectives

We investigated the perspective on workload within the Royal Netherlands Marechaussee, part of the Dutch armed forces.

Methods

This qualitative study follows an emergent design based on grounded theory principles and used semistructured interviews and focus groups with 91 Royal Netherlands Marechaussee employees. The interviews (n = 31) and focus groups (n = 14) were transcribed verbatim and analyzed by two researchers (C.B. and J.v.d.Z.) according to comparative data analysis.

Results

Participants believed the perception of workload to be more important than the actual workload. Furthermore, participants mentioned that indirect factors, such as organizational factors and recruitment, could modulate their workload perception.

Conclusions

The perception of workload is key within the context of the Royal Netherlands Marechaussee. Modifiable factors related to the perceived workload could facilitate employee well-being without reducing the actual workload.
Parotid Gland Microcystic Lymphatic Malformation Producing Obstructive Symptoms
Authors: Guhan Maya , Lambert Elton M. , Pezeshkmehr Amir , Rosenberg Tara L.
Published: February 2024

Background:

Salivary gland obstruction can present as unilateral, episodic facial swelling. Vascular malformations as a cause of parotid duct obstruction with associated unilateral cheek swelling and pain are rare.

Case description:

We describe the case of a 16-year-old female with a protracted 2-year history of unilateral facial swelling and pain that was misdiagnosed as recurrent parotitis on computed tomography and sialoendoscopy. Eventually, the 16-year-old female was diagnosed by magnetic resonance imaging to have a microcystic lymphatic malformation of the parotid duct as the cause of her cheek swelling and pain. Afterwards, the patient was referred to undergo interstitial bleomycin sclerotherapy.

Conclusions:

This case demonstrates a unique microcystic lymphatic malformation producing obstructive symptoms as well as the utility of magnetic resonance imaging for the diagnosis of a patient presenting with recurrent unilateral facial pain and swelling.
Clinical observation of Otitis Media Secretory during Covid-19
Authors: Liang Xiuni , Zhang Bei , Ding Ying , Guan Yafeng , Zhou Ping , Deng Yihong , Zeng Dan , Su Rongfei
Published: February 2024

Objective

This study aims to analyze the onset of otitis media secretory, the peak period of infection with the Omicron strain of SARS-CoV-2 virus, and the time of transmigration during a pandemic of the Omicron strain. Additionally, the study aims to investigate to study the presence of SARS-CoV-2 virus in the middle ear cavity of patients with otitis media secretory and the survival time through a new method for detecting SARS-CoV-2 virus antigen in middle ear effusion.

Methods

Retrospective comparison of the incidence of otitis media secretory during infection with SARS-CoV-2 virus Omicron strain from December 15, 2022, to January 15, 2023, versus the noninfection period from December 15, 2021, to January 15, 2022. We used a questionnaire star application to investigate the demographic and epidemiological characteristics of the 40 patients with otitis media secretory who participated in this study were investigated. A novel coronavirus (2019-nCoV) antigen detection kit (colloidal gold method) was used to detect middle ear effusion in patients with otitis media secretory. The data were statistically analyzed using SPSS 29.0 software. The measurement data are expressed as x ± s, the count data are expressed as the number of cases (%), and the data were compared using the χ2 test. p < 0.05 indicated a statistically significant difference.

Results

During the SARS-CoV-2 virus Omicron strain pandemic, the incidence of otitis media secretory increased by 15% compared with the noninfection period. The peak infection period for the SARS-CoV-2 virus Omicron strain was December 25, 2022, and December 15, 2022, and the peak time of conversion was 7 to 9 days after the infection. Middle ear effusion SARS-CoV-2 virus antigen testing was performed in patients with otitis media secretory after conversion; 5 patients (12%) were positive, and 35 patients (88%) were negative. The disease duration in patients with negative results was more than 3 weeks.

Conclusions

Otitis media secretory is one of the most common ear complications after infection with the Omicron strain of SARS-CoV-2 virus, and the significantly higher incidence is associated with middle ear viral infection. Middle ear effusion SARS-CoV-2 virus antigen test detected the virus, which survived longer in the middle ear effusion than in the nasal cavity. The middle ear effusion test can detect SARS-CoV-2 virus antigen and determine whether the organism contains virus residue.
Validation of noninvasive blood pressure monitoring function of EDAN elite V5 patient monitor with reference invasive measurement according to the ISO 81060-2:2018 standard
Authors: Wan Yi , Li Duan , Chen Jin-Feng , Zhang Yang
Published: February 2024

Objective

To validate the noninvasive blood pressure monitoring function of the EDAN elite V5 patient monitor with reference invasive blood pressure monitoring equipment for clinical use in adults, adolescents or children according to the International Organization for Standardization (ISO) 81060-2:2018 standard.

Methods

Patients were recruited, and the ipsilateral sequential method was used for blood pressure measurement according to the standard. The validation results were assessed following the protocol and the Bland–Altman scatterplot was used to show the difference between the test device and reference invasive blood pressure results.

Results

A total of 71 patients were included in the study, with 35 and 36 patients for each iFAST and iCUFS mode, respectively. The validation results showed an average device-reference difference of −3.27 ± 5.60 mmHg for SBP and −0.09 ± 6.10 mmHg for DBP for the iFAST mode, and −2.04 ± 5.55 mmHg for SBP and −0.79 ± 5.86 mmHg for DBP for the iCUFS mode, respectively, which passed the criteria of the ISO 81060-2 : 2018 in adults, adolescents or children population for both SBP and DBP.

Conclusion

The noninvasive blood pressure monitoring function of the EDAN elite V5 patient monitor passed all the requirements of ISO 81060-2:2018 and can be recommended for clinical use in adults, adolescents, or children.
Sex differences in the impact of body mass index on outcomes of coronary artery disease in Koreans
Authors: Kim Won-Jang , Lim Ha Jeong , Moon Jae Youn , Kim Sang-Hoon , Sung Jung-Hoon , Kim In Jai , Lim Sang-Wook , Cha Dong-Hun , Kang Se Hun
Published: February 2024

Background

Obesity is often considered a risk factor for cardiovascular disease, but recent studies have shown conflicting results regarding the effect of BMI on the prognosis of coronary artery disease (CAD). This study aimed to evaluate the relationship between BMI and clinical outcomes of CAD according to sex in a Korean population.

Methods

A total of 3476 patients with a significant CAD who underwent percutaneous coronary intervention (PCI) were enrolled. Patients were classified as follows according to BMI using the Asia–Pacific cutoff points: underweight (<18.5 kg/m2), normal weight (18.5–22.9 kg/m2), overweight (23.0–24.9 kg/m2) and obese (≥25 kg/m2) patients. Underweight and normal weight patients were further categorized into the lower BMI group, whereas overweight and obese patients were categorized into the higher BMI group. The primary endpoint was all-cause mortality.

Results

Among women, the higher BMI group showed poor clinical features in the prevalence of hypertension and chest pain presentation, and among men, the higher BMI group had a significantly lower rate of chronic renal failure. At the end of the follow-up period (median 53.5 months), the all-cause mortality rate was lower in the higher BMI group in men, and cardiovascular death and stroke rates were significantly lower in the higher BMI group in women.

Conclusion

In Korean CAD patients treated with PCI, inverse correlations were observed between the clinical outcomes and BMI, but there were differences between men and women.
Has the time come for age-adapted glomerular filtration rate criteria to define chronic kidney disease: how soon is now?
Authors: Hundemer Gregory L. , Akbari Ayub , Sood Manish M.
Published: February 2024

Purpose of review

The conventional definition of chronic kidney disease (CKD) primarily relies on the identification of albuminuria or a decline in estimated glomerular filtration rate (eGFR). For many years, a straightforward eGFR threshold of <60 ml/min/1.73 m2 has been widely adopted as the standard for defining CKD. Nonetheless, this criterion fails to consider the natural aging process of the kidney, and this oversight may affect the accurate diagnosis of kidney disease particularly at the extremes of age.

Recent findings

The fixed eGFR threshold of <60 ml/min/1.73 m2 for defining CKD misses crucial opportunities for risk prevention. Studies have revealed that the eGFR threshold at which the risks for adverse long-term health outcomes such as mortality, cardiovascular events, and kidney failure begin to rise varies substantially by age. Specifically, this threshold is lower for the elderly and higher for young adults. Consequently, this results in the over-diagnosis of kidney disease in the elderly and the under-diagnosis of kidney disease in young adults.

To address these limitations of the current CKD definition, we discuss a number of proposed age-adapted eGFR criteria and weigh their pros and cons against the current, simple, and universally accepted approach.
New therapies for immunoglobulin A nephropathy: what's the standard of care in 2023?
Authors: Barr Bryce , Barbour Sean
Published: February 2024

Purpose of review

As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently, therapeutic options were limited. Fortunately, there have been numerous recent clinical trials demonstrating efficacy of new therapies in slowing chronic kidney disease (CKD) progression at varying stages of disease.

Recent findings

The TESTING trial has provided high-quality evidence for slowing estimated glomerular filtration rate (eGFR) decline with a reduced-dose glucocorticoid regimen, while demonstrating an improved safety profile. Targeted-release budesonide represents a well tolerated therapy for reducing eGFR decline. Mycophenolate mofetil may reduce CKD progression in some populations, while hydroxychloroquine is efficacious in reducing proteinuria. Sodium-glucose cotransporter (SGLT2) inhibitors and sparsentan are effective therapies for CKD due to IgAN, but should not be used in lieu of disease-modifying immunosuppressive therapy. Many new therapies are approaching readiness for clinical use.

Numerous therapeutic options now exist and include disease-modifying and nephroprotective drugs. Identifying the right treatment for the right patient is now the clinical challenge and, with new drugs on the horizon, represents the primary unmet research need in this rapidly-developing field.
Updates on the clinical integration of point-of-care ultrasound in pediatric emergency medicine
Authors: Lee Michelle Sin , Sweetnam-Holmes Danielle , Soffer Gili Palnizky , Harel-Sterling Maya
Published: February 2024

Purpose of review

There is expanding evidence for point-of-care ultrasound (POCUS) use in pediatric emergency medicine – this review highlights the benefits and challenges in the clinical integration of high-yield POCUS applications. Specifically, it will delve into POCUS applications during resuscitations, controversies of Focused Assessment with Sonography for Trauma (FAST) in pediatric trauma, POCUS-guided procedures, and examples of clinical pathways where POCUS can expedite definitive care.

Recent findings

POCUS can enhance diagnostic accuracy and aid in management of pediatric patients in shock and help identify reversible causes during cardiac arrest. The use of the FAST in pediatric blunt abdominal trauma remains nuanced – its proper use requires an integration with clinical findings and an appreciation of its limitations. POCUS has been shown to enhance safety and efficacy of procedures such as nerve blocks, incision & drainage, and intravenous access. Integrating POCUS into pathways for conditions such as intussusception and testicular torsion expedites downstream care.

POCUS enhances diagnostic efficiency and management in pediatric patients arriving at the ED with undifferentiated shock, cardiac arrest, or trauma. Additionally, POCUS improves procedural success and safety, and is integral to clinical pathways for expediting definitive care for various pediatric emergencies. Future research should continue to focus on the impact of POCUS on patient outcomes, ensuring user competency, and the expansion of POCUS into diverse settings.
Ileocecal knotting as a rare cause of small bowel obstruction: a case report
Authors: Dallakoti Nishanta , Pant Ved Prakash , Pokhrel Nabin , Bhatta Prashant , Rana Vijay Kumar , Sah Rupesh Prasad
Published: February 2024

Introduction:

Ileocecal knot syndrome, a rare cause of small bowel obstruction where the ileum wraps around the cecum, poses a significant challenge for preoperative diagnosis. Prompt intervention is crucial due to the risk of rapid bowel deterioration and increased mortality.

Case presentation:

A 45-year-old female presented with central abdominal pain associated with vomiting, abdominal distension, and obstipation. On examination, she was ill-looking with hypotension, tachycardia with a feeble pulse, direct and rebound abdominal tenderness, and absent bowel sounds. Aggressive fluid resuscitation was done. Based on the clinical presentation and abdominal radiograph suggestive of intestinal obstruction, an emergency exploratory laparotomy was done, which showed an ileocecal knot and 130 cm of gangrenous ileum. Peritoneal lavage followed by resection of non-viable ileum with double barrel ileostomy was done.

Discussion:

Ileosigmoid, appendico-ileal, ileoileal, and ileocecal knotting are the various types of intestinal knotting, with very few cases of ileocecal knotting being reported. Intestinal knotting causes severe bowel obstruction, resulting in reduced mucosal perfusion, progressive ischemia, and peritonitis, leading to high mortality. X-ray findings of multiple air-fluid levels are non-specific, and for definitive diagnosis, laparotomy is required. Assessing bowel viability before definitive surgery is essential. Despite positive outcomes, extensive resection can lead to malabsorption and ileus, with potential risk for developing short bowel syndrome.

Conclusion:

Despite its rarity, the possibility of ileocecal knotting should be considered in cases of small bowel obstruction due to its potential for rapid deterioration. Prompt resuscitation followed by emergency laparotomy is necessary to prevent mortality.
PET/CT in a 65-Year-Old Woman With Epstein-Barr Virus–Associated Smooth Muscle Tumor After Chemotherapy for Follicular Lymphoma
Authors: Wu Chia-Shang , Wen Yu-Ching , Chen Wei-Yu , Chiou Tzeon-Jye
Published: February 2024

The Epstein-Barr virus–associated smooth muscle tumor (SMT) is an uncommon neoplasm. It arises mainly in 3 immunosuppression settings: HIV-associated SMT; drug-related immunosuppression in transplant recipients; and congenital immunodeficiency disorder–associated SMT. We present 18F-FDG PET/CT findings of an adrenal Epstein-Barr virus–associated SMT in a 65-year-old woman with a history of follicular lymphoma after chemotherapy.
Medial Epicanthal Fold Correction Using a Y-W Epicanthoplasty in Asian Eyelids
Authors: Park Hojin , Moon Yijun , Kim Da Som , Park Seung Ha
Published: February 2024

Many surgical techniques for managing epicanthal folds have been reported, but their main drawbacks include a noticeable scar in Asians, acute medial canthal angle, and applicability only in mild or moderate epicanthal folds. This study described a novel surgical technique, Y-W epicanthoplasty, and assessed the medial canthal shape and scarring in patients who underwent Y-W epicanthoplasty. Patients with moderate or severe epicanthal folds between January 2004 and February 2017 were included in this study. Pre- and postoperative intercanthal distance (ICD), inner canthal angle (ICA), and interpupillary distance (IPD) were measured. The ICD ratios (ICD/IPD) and extent of postoperative scarring were evaluated. A Y-W epicanthoplasty was performed on 18 patients. The ICD ratio of the total study cohort showed a significant reduction following surgery (preoperative ICD ratio=0.62±0.04, postoperative ICD ratio=0.58±0.03, P<0.001). The ICA was 51.8±7.7° and 49.8±5.6° in the pre- and postoperative periods, respectively (P=0.086) Eleven patients showed no apparent scar, and 6 patients were found to have minimal scarring that was visible only under close inspection. One patient had a hypertrophic scar that was successfully managed with triamcinolone acetonide injections. Y-W epicanthoplasty can provide good aesthetic results without a visible scar in patients with moderate-to-severe epicanthal folds. The Y-W epicanthoplasty avoids a medially extended skin incision and excessive tension on the skin flaps. Moreover, an acutely shaped or webbed medial canthus after epicanthoplasty can be prevented by adding a small triangular flap. The Y-W epicanthoplasty procedure is simple and straightforward, and it is appropriate for moderate-to-severe epicanthal fold correction.
Tuning a mechanical model to biological reality: A case study in the LaMSA system of the trap-jaw antStrumigenys
Authors: Anderson Philip S L , Jorge Justin F , Crofts Stephanie B , Castro Jackson T , Didcock Rosalie L , Cook Andrés , Larabee Fredrick J , Ilton Mark
Published: February 2024

Understanding the relationship between morphology and movement in biomechanical systems, particularly those composed of multiple complex elements, presents challenges due to the nonlinear nature of the interaction between components. This study focuses on the mandibular closing mechanisms in ants, specifically comparing muscle-driven actuation (MDA) and latch-mediated spring actuation (LaMSA) in the genusStrumigenys. Analyzing 3D structural data from diverseStrumigenysspecies, we employ mathematical models for both LaMSA and MDA systems. Our findings reveal distinct patterns of mechanical sensitivity between the two models, with sensitivity varying across kinematic output metrics. We explore the performance transition between MDA and LaMSA systems by incorporating biological data and correlations between morphological parameters into the models. In these models tuned specifically toStrumigenys, we find the LaMSA mechanism outperforms MDA at small relative mandible mass. Notably, the location and abruptness of the performance transition differs among various kinematic performance metrics. Overall, this work contributes a novel approach to understanding form-function relationships in complex biomechanical systems. By using morphological data to calibrate a general biomechanical model for a particular group, it strikes a balance between simplicity and specificity and allows for conclusions that are uniquely tuned to the morphological characteristics of the group.
Multimodal classification of neurons in the lateral septum
Authors: Reid Christopher M. , Ren Yuqi , Xie Yajun , Garcίa Miguel Turrero , Tran Diana , Vu Steve , Liu Jonathan , Adam Manal A. , Hanson Sarah M. , Pisco Angela O. , Harwell Corey C.
Published: February 2024

The lateral septum (LS) is a nucleus in the ventral forebrain that modulates complex social and affective behaviors. Several distinct neuronal types have been described in the LS; however, the full extent of this cellular and molecular diversity remains unclear. We address this gap by profiling the transcriptional identity of mature LS neurons originating from two progenitor lineages defined by their anatomical location and expression of the transcription factorNkx2.1. We describe 12 molecularly distinct subtypes of LS neurons that fall into two main groups: those with a history ofNkx2.1expression and those without. We discovered that LS neurons from theNkx2.1lineage share an enrichment of select cell adhesion and communication molecules. Despite this, we found that LS neurons that have distinct developmental origins can exhibit significant transcriptional similarities. We then examined the spatial relationships among neurons in the LS, revealing that each subtype occupies a discrete anatomical domain. These anatomical domains are defined by graded patterns of gene expression that correlate with the molecular taxonomy of LS neuron subtypes and encode proteins involved in synaptic signaling. Lastly, we genetically labeled non-overlapping subgroups of LS neurons, and detailed their connective, morphological, and electrophysiological properties. Our findings offer a deeper understanding of neuronal heterogeneity in the LS, paving the way for future studies into how these neuronal types contribute to regulating emotional and motivated behaviors.
Across Thermal Scales: Quantized Thermodynamics, Nested Resonant Structures, and the Entropic Stability of Life
Authors: Baker Josh E.
Published: February 2024

Biological systems are fundamentally containers of thermally fluctuating atoms that through unknown mechanisms are structurally layered across many thermal scales from atoms to amino acids to primary, secondary, and tertiary structures to functional proteins to functional macromolecular assemblies and up. Understanding how chemical thermodynamics sc ales across these layered structures is central to describing biological structure and function. Muscle – with chemical thermodynamics well-defined on two different thermal scales – provides a clear solution to this problem. In 1938, A.V. Hill made the extraordinary observation that the mechanics and chemistry of muscle contraction is defined independent of the structural components of muscle, implying that the mechanics and chemistry of myosin motor proteins within muscle do not classically scale up to muscle. We have demonstrated experimentally that thermal scaling bridges Hill’s top-down thermodynamics and the bottom-up philosophy of molecular biologists. That is, with thermal scalingNindividual myosin motor switches physically collapse into an ensemble ofNmyosin motor switches creating a functional entropy within the ensemble well defined by the statistical mechanics of a binary system of switches. This ensemble entropy stabilizes the resonant ensemble structure of muscle and energetically drives the irreversible kinetics and energetics of muscle contraction. Here I develop a general model of thermal scaling and show that it occurs when the ensemble state of a system is defined, at which point the number of ways constituent molecules can account for the ensemble state contributes to the entropy of the ensemble state. At that point, the statistical occupancy of molecular states physically replaces the physical occupancy of molecular states. This is not a classical mechanism and as shown here results in many quantum-like phenomena, which consistent with Hill’s observation means that biological function cannot be described by classical molecular mechanisms.
Non-canonical Metabolic and Molecular Effects of Calorie Restriction Are Revealed by Varying Temporal Conditions
Authors: Pak Heidi H. , Grossberg Allison N. , Sanderfoot Rachel R. , Babygirija Reji , Green Cara L. , Koller Mikaela , Dzieciatkowska Monika , Paredes Daniel A. , Lamming Dudley W.
Published: February 2024

Calorie restriction (CR) extends lifespan and healthspan in diverse species. However, comparingad libitum(AL) and CR-fed mice is challenging due to their significantly different feeding patterns. CR-fed mice consume their daily meal in approximately 2 hours, subjecting themselves to a prolonged self-imposed fast each day. To gain deeper insights into the effects of CR, we conducted a comprehensive examination of how AL and CR-fed mice respond to tests performed at various times relative to the completion of their once-daily CR meal. Our findings reveal that many well-known effects of CR, including its impact on insulin sensitivity, result from the specific temporal conditions. CR animals exhibit a divergent response to insulin, and this response varies based on the time elapsed since the CR-fed mice consumed their food. Utilizing an unbiased metabolomics approach, we discovered that the effects of CR on circulating metabolites are heavily dependent upon the time-of-day and feeding regimen. Finally, while it is widely believed that CR functions in part by reducing activity of the kinase mTORC1, our study suggests that the observed differences in mTORC1 activity between AL and CR-fed mice are dependent upon both fasting duration and the specific tissue examined. Furthermore, we find that the metabolic effects of CR are independent of hepatic mTORC1. Our results shed new light on the physiological, metabolic, and molecular effects of a CR diet, and highlight that much of our understanding of the effects of CR are related to when, relative to feeding, we choose to examine the mice.