bluuebunny/crossref_metadata_2025 huggingface dataset:
Household chaos and childhood obesity-related health outcomes
Authors: Burton E Thomaseo , Choquette Adora E , Gray Emily , Odulana Adebowale , Kim Ahlee , Smith Webb A
Published: July 2024

Objective

Household chaos, defined as a lack of organization, structure, and predictability, has been linked to deleterious childhood health outcomes and may hinder attempts to initiate and maintain healthy lifestyle changes. This study examined the associations of household chaos and obesity-related health conditions in a sample of youth being treated for obesity.

Methods

Participants were 715 patients (61.8% girls; Mage = 12.3 years; 68.7% non-Hispanic Black; M% of 95th BMI %-ile = 146.9%) enrolled in a pediatric weight management clinic. Caregiver report of household chaos was measured using the Confusion, Hubbub and Order Scale (CHAOS). Physiological obesity-related comorbidities (e.g., insulin resistance, hypertension, dyslipidemia) were assessed by a medical clinician and abstracted from electronic medical records; health conditions were dichotomized as present or not present. Psychological functioning was measured with the Pediatric Symptom Checklist, a caregiver-completed mental health screen that assesses internalizing, externalizing, and attention concerns.

Results

The Wilcoxon rank-sum test was used to test differences in household chaos scores for each obesity-related health condition. Caregivers of youth diagnosed with hypertension and obstructive sleep apnea reported significantly lower levels of household chaos, while caregivers who reported clinical levels of psychological dysfunction reported higher levels of chaos.

Conclusions

Traditional management of childhood obesity requires changes across multiple health domains (e.g., dietary, exercise, sleep), and such change may be facilitated by structure and consistency. Present findings suggest that psychological resources within pediatric weight management settings should address individual patient-level factors associated with physiological and mental health as well as household functioning.
The X-ray rise and fall of the symbiotic recurrent nova system T CrB
Authors: Toalá Jesús A , González-Martín Omaira , Sacchi Andrea , Vasquez-Torres Diego A
Published: July 2024

We present the analysis of publicly available NuSTAR, Suzaku, and XMM–Newton observations of the symbiotic recurrent nova T CrB covering the 2006.77–2022.66 yr period. The X-ray spectra are analysed by adopting a model that includes a reflection component produced by the presence of a disc that mimics the accretion disc and the immediate surrounding medium. Our best-fitting model requires this disc to have a radius of 1 au, effective thickness of 0.1 au, averaged column density 10$^{25}$ cm$^{-2}$ and orientation of 50$^{\circ }$ with respect to the line of sight. This disc is about a factor of two larger than recent estimations for the accretion disc and its presence contributes significantly via reflection to the total X-ray flux detected from T CrB, which naturally produces the emission of the 6.4 keV Fe line. Our analysis suggests that the temperature of the boundary layer evolved from 14.8 keV in the steady-state phase (before 2016), to 2.8 keV in the 2017.24 epoch, to finally stabilize to about $\sim$8 keV in the subsequent epochs. These variations in the plasma temperature of the boundary layer are attributed to the evolution of the mass accretion rate ($\dot{M}_\mathrm{acc}$), which is estimated to have an averaged value of $\dot{M}_\mathrm{acc}$ = 2.6$\times \,10^{-8}$ M$_\odot$ yr$^{-1}$ for the current active phase. The presence of emission lines in the XMM–Newton Reflection Grating Spectrometer spectrum of 2017.24 prevents from adopting a blackbody emission model to fit the soft X-ray range. Instead, we use plasma emission models that suggest the presence of adiabatically shocked gas produced by gas velocities of 110–200 km s$^{-1}$, very likely tracing jet-like ejections similar to what is found in other symbiotic systems. The analysis of X-ray and optical data together show that T CrB has a similar evolution as black hole binaries, accreting neutron stars and active galactic nuclei in the hardness–intensity diagram.
The three-dimensional structure of black hole accretion flows within the plunging region
Authors: Mummery Andrew , Stone James M
Published: July 2024

We analyse, using new analytical models and numerical general relativistic magnetohydrodynamic simulations, the three-dimensional properties of accretion flows inside the plunging region of black hole spacetimes (i.e. at radii smaller than the innermost stable circular orbit). These simulations are of thick discs, with aspect ratios of order unity $h/r \sim 1$, and with a magnetic field geometry given by the standard low-magnetization ‘SANE’ configuration. This work represents the first step in a wider analysis of this highly relativistic region. We show that analytical expressions derived in the ‘thin disc’ limit describe the numerical results remarkably well, despite the large aspect ratio of the flow. We further demonstrate that accretion within this region is typically mediated via spiral arms, and that the geometric properties of these spiral structures can be understood with a simple analytical model. These results highlight how accretion within the plunging region is fundamentally two-dimensional in character, which may have a number of observational implications. We derive a modified theoretical description of the pressure within the plunging region which accounts for turbulent heating and may be of use to black hole image modelling.
Diffuse glioma molecular profiling with arterial spin labeling and dynamic susceptibility contrast perfusion MRI: A comparative study
Authors: Prysiazhniuk Yeva , Server Andres , Leske Henning , Bech-Aase Øystein , Helseth Eirik , Eijgelaar Roelant Sjouke , Fuster-García Elies , Brandal Petter , Bjørnerud Atle , Otáhal Jakub , Petr Jan , Nordhøy Wibeke
Published: July 2024

Background

Evaluation of molecular markers (IDH, pTERT, 1p/19q codeletion, and MGMT) in adult diffuse gliomas is crucial for accurate diagnosis and optimal treatment planning. Dynamic Susceptibility Contrast (DSC) and Arterial Spin Labeling (ASL) perfusion MRI techniques have both shown good performance in classifying molecular markers, however, their performance has not been compared side-by-side.

Methods

Pretreatment MRI data from 90 patients diagnosed with diffuse glioma (54 men/36 female, 53.1 ± 15.5 years, grades 2–4) were retrospectively analyzed. DSC-derived normalized cerebral blood flow/volume (nCBF/nCBV) and ASL-derived nCBF in tumor and perifocal edema were analyzed in patients with available IDH-mutation (n = 67), pTERT-mutation (n = 39), 1p/19q codeletion (n = 33), and MGMT promoter methylation (n = 31) status. Cross-validated uni- and multivariate logistic regression models assessed perfusion parameters’ performance in molecular marker detection.

Results

ASL and DSC perfusion parameters in tumor and edema distinguished IDH-wildtype (wt) and pTERT-wt tumors from mutated ones. Univariate classification performance was comparable for ASL-nCBF and DSC-nCBV in IDH (maximum AUROCC 0.82 and 0.83, respectively) and pTERT (maximum AUROCC 0.70 and 0.81, respectively) status differentiation. The multivariate approach improved IDH (DSC-nCBV AUROCC 0.89) and pTERT (ASL-nCBF AUROCC 0.8 and DSC-nCBV AUROCC 0.86) classification. However, ASL and DSC parameters could not differentiate 1p/19q codeletion or MGMT promoter methylation status. Positive correlations were found between ASL-nCBF and DSC-nCBV/-nCBF in tumor and edema.

Conclusions

ASL is a viable gadolinium-free replacement for DSC for molecular characterization of adult diffuse gliomas.
The Frequently Used Industrial Food Process Additive, Microbial Transglutaminase: Boon or Bane
Authors: Lerner Aaron , Benzvi Carina , Vojdani Aristo
Published: July 2024

Microbial transglutaminase (mTG) is a frequently consumed processed food additive, and use of its cross-linked complexes is expanding rapidly. It was designated as a processing aid and was granted the generally recognized as safe (GRAS) classification decades ago, thus avoiding thorough assessment according to current criteria of toxicity and public health safety. In contrast to the manufacturer's declarations and claims, mTG and/or its transamidated complexes are proinflammatory, immunogenic, allergenic, pathogenic, and potentially toxic, hence raising concerns for public health. Being a member of the transglutaminase family and functionally imitating the tissue transglutaminase, mTG was recently identified as a potential inducer of celiac disease. Microbial transglutaminase and its docked complexes have numerous detrimental effects. Those harmful aspects are denied by the manufacturers, who claim the enzyme is deactivated when heated or by gastric acidity, and that its covalently linked isopeptide bonds are safe. The present narrative review describes the potential side effects of mTG, highlighting its thermostability and activity over a broad pH range, thus, challenging the manufacturers' and distributers' safety claims. The national food regulatory authorities and the scientific community are urged to reevaluate mTG's GRAS status, prioritizing public health protection against the possible risks associated with this enzyme and its health-damaging consequences.
Tyrosine phenol-lyase inhibitor quercetin reduces fecal phenol levels in mice
Authors: Kobayashi Takuma , Oishi Shiori , Matsui Misaki , Hara Kodai , Hashimoto Hiroshi , Watanabe Kenji , Yoshioka Yasukiyo , Miyoshi Noriyuki
Published: July 2024

Tyrosine phenol-lyase (TPL), which is expressed in intestinal bacteria, catalyzes the formation of phenol from the substrate L-Tyr. Bacterial metabolite phenol and the sulfate conjugate (phenyl sulfate) are known as a type of uremic toxins, some of which exert cytotoxicity. Therefore, pathologically elevated phenol and phenyl sulfate levels are strongly implicated in the etiology and outcome of uremia. In this study, we explored the inhibitory effects of dietary polyphenols on TPL-catalyzed phenol production using a TPL activity assay. Quercetin, one of the most popular polyphenols, exhibited the strongest inhibitory activity (Ki = 19.9 µM). Quercetin competitively inhibited TPL, and its activity was stronger than that of a known TPL inhibitor (Tyr analog; 2-aza-Tyr, Ki = 42.0 µM). Additionally, quercetin significantly inhibited phenol production in TPL-expressing bacterial cultures (Morganella morganii and Citrobacter koseri) and Tyr-rich (5%) diet-fed C57BL/6J mouse feces. Our findings suggest that quercetin is the most promising polyphenol for reducing phenol levels. Because quercetin has a low gastrointestinal absorption rate, TPL inhibition in the intestinal tract by quercetin may be an effective strategy for treating uremia.
Deep Generative Model of the Distal Tibial Classic Metaphyseal Lesion in Infants: Assessment of Synthetic Images
Authors: Wu Shaoju , Kurugol Sila , Kleinman Paul K , Ecklund Kirsten , Walters Michele , Connolly Susan A , Johnston Patrick , Tsai Andy
Published: July 2024

Background

The classic metaphyseal lesion (CML) is a distinctive fracture highly specific to infant abuse. To increase the size and diversity of the training CML database for automated deep-learning detection of this fracture, we developed a mask conditional diffusion model (MaC-DM) to generate synthetic images with and without CMLs.

Purpose

To objectively and subjectively assess the synthetic radiographic images with and without CMLs generated by MaC-DM.

Materials and Methods

For retrospective testing, we randomly chose 100 real images (50 normals and 50 with CMLs; 39 infants, male = 22, female = 17; mean age = 4.1 months; SD = 3.1 months) from an existing distal tibia dataset (177 normal, 73 with CMLs), and generated 100 synthetic distal tibia images via MaC-DM (50 normals and 50 with CMLs). These test images were shown to three blinded radiologists. In the 1st session, radiologists determined if the images were normal or had CMLs. In the 2nd session, they determined if the images were real or synthetic. We analyzed the radiologists’ interpretations, and employed t-distributed stochastic neighbor embedding (t-SNE) technique to analyze the data distribution of the test images.

Results

When presented with the 200 images (100 synthetic, 100 with CMLs), radiologists reliably and accurately diagnosed CMLs (kappa = 0.90, 95% CI = [0.88, 0.92]; accuracy = 92%, 95% CI = [89%, 97%]). However, they were inaccurate in differentiating between real and synthetic images (kappa = 0.05, 95% CI = [0.03, 0.07]; accuracy = 53%, 95% CI = [49%, 59%]). The t-SNE analysis showed substantial differences in the data distribution between normal images and those with CMLs (AUC = 0.996, 95% CI = [0.992, 1.000], P < 0.01), but minor differences between real and synthetic images (AUC = 0.566, 95% CI = [0.486, 0.647], P = 0.11).

Conclusion

Radiologists accurately diagnosed images with distal tibial CMLs but were unable to distinguish real from synthetically generated ones, indicating that our generative model could synthesize realistic images. Thus, MaC-DM holds promise as an effective strategy for data augmentation in training machine-learning models for diagnosis of distal tibial CMLs.
Housing Market Appreciation and the White-Black Wealth Gap
Authors: LaBriola Joe
Published: July 2024

Real house prices in the United States have risen by 55 percent over the last four decades, driving substantial wealth benefits to homeowners. However, research has not explored how this rise in house prices has affected White-Black wealth gaps, or the mechanisms that may underlie this relationship. Using geocoded longitudinal household-level wealth data from the Panel Study of Income Dynamics and tract-level house price index data, I estimate that housing market appreciation between 1984 and 2021 explains 70 percent of the increase in the median White-Black wealth gap over this period. I find that most of this effect is due to White-Black gaps in homeownership, with White-Black gaps in house values playing a smaller role. In contrast to recent findings about racialized housing markets, I do not find that gaps in neighborhood house price appreciation between White and Black homeowners contributed to White-Black wealth gaps in the 2000s and 2010s. These results highlight the importance of cumulative advantage processes in driving wealth inequalities and demonstrate how the legacies of institutional racism contribute to contemporary racial wealth gaps.
Sevoflurane augments neuroinflammation by regulating DUSP6 via YTHDF1 in postoperative cognitive dysfunction
Authors: Ding Jie , Zhang Kai , Wang DongWei , Wang QingDong
Published: July 2024

Background

Postoperative cognitive dysfunction (POCD) is a generally recognized complication experienced by patients who receive anesthesia during surgery. Sevoflurane, the most commonly used inhaled anesthetic, has been shown to trigger neuroinflammation that promotes to POCD.

Objective

This study examined the pathological mechanism by which sevoflurane causes neuroinflammation, participating in POCD.

Methods

To establish a neurocyte injury model, the human neuroblastoma cell lines SH-SY5Y and SK-N-SH were treated with sevoflurane. Cell viability was determined using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays. The reactive oxygen species (ROS) level was evaluated by DCFH-DA assays. A lactate dehydrogenase (LDH) Cytotoxicity Assay Kit was used to measure LDH levels. Inflammatory cytokine levels were measured using enzyme-linked immunosorbent assay assays. Gene expression densities and protein abundance were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) or western blotting. The interaction between YTHDF1 and dual specific phosphatase 6 (DUSP6) was validated using RNA immunoprecipitation (RIP)-qPCR and methylated RIP (MeRIP)-qPCR assays. Flow cytometry was performed to determine apoptosis.

Results

Sevoflurane promoted apoptosis, oxidative stress, and neuroinflammation and repressed the expression levels of YTHDF1 and DUSP6. Furthermore, YTHDF1 overexpression reversed sevoflurane-induced neuroinflammation in neurocytes. DUSP6 overexpression could alleviate the neuroinflammation induced by sevoflurane via regulating the extracellular signal-regulated kinase (ERK)1/2 signaling pathway. Moreover, YTHDF1 enhanced DUSP6 expression.

Conclusion

Sevoflurane-stimulated neuroinflammation by regulating DUSP6 via YTHDF1. Sevoflurane promoted neuroinflammation by regulating DUSP6 via YTHDF1 in an in vitro model of POCD.
Identifying assessment criteria for in vitro studies: a method and item bank
Authors: Whaley Paul , Blain Robyn B , Draper Derek , Rooney Andrew A , Walker Vickie R , Wattam Stephen , Wright Rob , Hooijmans Carlijn R
Published: July 2024

To support the development of appraisal tools for assessing the quality of in vitro studies, we developed a method for literature-based discovery of study assessment criteria, used the method to create an item bank of assessment criteria of potential relevance to in vitro studies, and analyzed the item bank to discern and critique current approaches for appraisal of in vitro studies. We searched four research indexes and included any document that identified itself as an appraisal tool for in vitro studies, was a systematic review that included a critical appraisal step, or was a reporting checklist for in vitro studies. We abstracted, normalized, and categorized all criteria applied by the included appraisal tools to create an “item bank” database of issues relevant to the assessment of in vitro studies. The resulting item bank consists of 676 unique appraisal concepts from 67 appraisal tools. We believe this item bank is the single most comprehensive resource of its type to date, should be of high utility for future tool development exercises, and provides a robust methodology for grounding tool development in the existing literature. Although we set out to develop an item bank specifically targeting in vitro studies, we found that many of the assessment concepts we discovered are readily applicable to other study designs. Item banks can be of significant value as a resource; however, there are important challenges in developing, maintaining, and extending them of which researchers should be aware.
Artificial intelligence and human rights
Authors: Kamble R M
Published: July 2024

Artificial intelligence (AI) has become an ever-increasing necessity in day-to-day life. Technology can be a powerful tool for human rights. As rightly quoted by John F. Kennedy, ‘the rights of every man are diminished when the right of one man is threatened....’. The present article focuses on a brief history and also on various types of AI. The issue of whether AI is beneficial or detrimental for human rights has a direct relationship with the overall impact of AI on human beings. This article discusses the issue of AI and its lacunas and various challenges that will have adverse effects on human rights. The article also highlights the positive and negative aspects of this and its impact on society as well as on the perspective of human rights. The article further briefly discusses the implementation of AI in the judicial system.
Chiefs, Courts, and Upholding Property Rights: Quasi-Experimental Evidence from Sierra Leone
Authors: Kpaka Henry Musa
Published: July 2024

Land disputes are unavoidable and costly to resolve in the formal courts in contexts with weak property rights and low state capacity. In order to relax the pressure on strained formal courts, many countries permit parallel informal dispute-resolution forums. This paper studies the extent to which one such forum—Chiefdom Land Committees (CLCs)—in Sierra Leone is able to resolve land disputes. This paper constructs a data set of ligated cases at local courts across the country and implements a difference-in-difference design to estimate the effect of the CLCs on land caseload in the formal courts. Contrary to the policy goals, this paper finds that on average, chiefdoms with CLCs have higher land caseload in the formal courts three years on. By adopting the CLCs, chiefdoms plausibly made land issues more salient, but, instead of providing final resolutions, CLCs are conduits for the formalization of land disputes.
THUMPD3‐AS1 inhibits ovarian cancer cell apoptosis through the miR‐320d/ARF1 axis
Authors: Mu Qingling , Wang Xin , Huang Kui , Xia Baoguo , Bi Shuna , Kong Yujie
Published: July 2024

Ovarian cancer is one of the most common gynecologic malignancies that has a poor prognosis. THUMPD3‐AS1 is an oncogenic long noncoding RNA (lncRNA) in several cancers. Moreover, miR‐320d is downregulated and inhibited proliferation in ovarian cancer cells, whereas ARF1 was upregulated and promoted the malignant progression in epithelial ovarian cancer. Nevertheless, the role of THUMPD3‐AS1 in ovarian cancer and the underlying mechanism has yet to be elucidated. Human normal ovarian epithelial cells (IOSE80) and ovarian cancer cell lines (CAVO3, A2780, SKOV3, OVCAR3, and HEY) were adopted for in vitro experiments. The functional roles of THUMPD3‐AS1 in cell viability and apoptosis were determined using CCK‐8, flow cytometry, and TUNEL assays. Western blot was performed to assess the protein levels of ARF1, Bax, Bcl‐2, and caspase 3, whereas RT‐qPCR was applied to measure ARF1 mRNA, THUMPD3‐AS1, and miR‐320d levels. The targeting relationship between miR‐320d and THUMPD3‐AS1 or ARF1 was validated with dual luciferase assay. THUMPD3‐AS1 and ARF1 were highly expressed in ovarian cancer cells, whereas miR‐320d level was lowly expressed. THUMPD3‐AS1 knockdown was able to repress cell viability and accelerate apoptosis of OVCAR3 and SKOV3 cells. Also, THUMPD3‐AS1 acted as a sponge of miR‐320d, preventing the degradation of ARF1. MiR‐320d downregulation reversed the tumor suppressive function induced by THUMPD3‐AS1 depletion. Additionally, miR‐320d overexpression inhibited ovarian cancer cell viability and accelerated apoptosis, which was overturned by overexpression of ARF1. THUMPD3‐AS1 inhibited ovarian cancer cell apoptosis by modulation of miR‐320d/ARF1 axis. The discoveries might provide a prospective target for ovarian cancer treatment.
Tumor‐associated genetic amplifications impact extracellular vesicle miRNA cargo and their recruitment of nerves in head and neck cancer
Authors: Restaino Anthony C. , Walz Austin , Barclay Sarah M. , Fettig Robin R. , Vermeer Paola D.
Published: July 2024

Cancer neuroscience is an emerging field of cancer biology focused on defining the interactions and relationships between the nervous system, developing malignancies, and their environments. Our previous work demonstrates that small extracellular vesicles (sEVs) released by head and neck squamous cell carcinomas (HNSCCs) recruit loco‐regional nerves to the tumor. sEVs contain a diverse collection of biological cargo, including microRNAs (miRNAs). Here, we asked whether two genes commonly amplified in HNSCC, CCND1, and PIK3CA, impact the sEV miRNA cargo and, subsequently, sEV‐mediated tumor innervation. To test this, we individually overexpressed these genes in a syngeneic murine HNSCC cell line, purified their sEVs, and tested their neurite outgrowth activity on dorsal root ganglia (DRG) neurons in vitro. sEVs purified from Ccnd1‐overexpressing cells significantly increased neurite outgrowth of DRG compared to sEVs from parental or Pik3ca over‐expressing cells. When implanted into C57BL/6 mice, Ccnd1 over‐expressing tumor cells promoted significantly more tumor innervation in vivo. qPCR analysis of sEVs shows that increased expression of Ccnd1 altered the packaging of miRNAs (miR‐15‐5p, miR‐17‐5p, and miR‐21‐5p), many of which target transcripts important in regulating axonogenesis. These data indicate that genetic amplifications harbored by malignancies impose changes in sEV miRNA cargo, which can influence tumorc innervation.
Intermittent hypoxia exacerbates metabolic dysfunction‐associated fatty liver disease by aggravating hepatic copper deficiency‐induced ferroptosis
Authors: Wang Ruhua , Lv Yuerong , Ni ZiYan , Feng Wei , Fan Pei , Wang Yan , Lin Yiguang , Chen Xueqing
Published: July 2024

Intermittent hypoxia (IH) is an independent risk factor for metabolic dysfunction‐associated fatty liver disease (MAFLD). Copper deficiency can disrupt redox homeostasis, iron, and lipid metabolism. Here, we investigated whether hepatic copper deficiency plays a role in IH‐associated MAFLD and explored the underlying mechanism(s). Male C57BL/6 mice were fed a western‐type diet with adequate copper (CuA) or marginally deficient copper (CuD) and were exposed separately to room air (RA) or IH. Hepatic histology, plasma biomarkers, copper–iron status, and oxidative stress were assessed. An in vitro HepG2 cell lipotoxicity model and proteomic analysis were used to elucidate the specific targets involved. We observed that there were no differences in hepatic phenotypes between CuA‐fed and CuD‐fed mice under RA. However, in IH exposure, CuD‐fed mice showed more pronounced hepatic steatosis, liver injury, and oxidative stress than CuA‐fed mice. IH induced copper accumulation in the brain and heart and exacerbated hepatic copper deficiency and secondary iron deposition. In vitro, CuD‐treated cells with IH exposure showed elevated levels of lipid accumulation, oxidative stress, and ferroptosis susceptibility. Proteomic analysis identified 360 upregulated and 359 downregulated differentially expressed proteins between CuA and CuD groups under IH; these proteins were mainly enriched in citrate cycle, oxidative phosphorylation, fatty acid metabolism, the peroxisome proliferator‐activated receptor (PPAR)α pathway, and ferroptosis. In IH exposure, CuD significantly upregulated the ferroptosis‐promoting factor arachidonyl‐CoA synthetase long chain family member (ACSL)4. ACSL4 knockdown markedly eliminated CuD‐induced ferroptosis and lipid accumulation in IH exposure. In conculsion, IH can lead to reduced hepatic copper reserves and secondary iron deposition, thereby inducing ferroptosis and subsequent MAFLD progression. Insufficient dietary copper may worsen IH‐associated MAFLD.
Interpretable Machine Learning Models Based on Shapley Additive Explanations for Predicting the Risk of Cerebrospinal Fluid Leakage in Lumbar Fusion Surgery
Authors: Guo ZongJie , Wang PeiYang , Ye SuHui , Li HaoYu , Bao JunPing , Shi Rui , Yang Shu , Yin Rui , Wu XiaoTao
Published: July 2024

Study Design.

Retrospective study.

Objectives.

The objective of this investigation was to formulate and internally verify a customized machine learning (ML) framework for forecasting cerebrospinal fluid leakage (CSFL) in lumbar fusion surgery. This was accomplished by integrating imaging parameters and using the SHapley Additive exPlanation (SHAP) technique to elucidate the interpretability of the model.

Summary of Background Data.

Given the increasing incidence and surgical volume of spinal degeneration worldwide, accurate predictions of postoperative complications are urgently needed. SHAP-based interpretable ML models have not been used for CSFL risk factor analysis in lumbar fusion surgery.

Methods.

Clinical and imaging data were retrospectively collected from 3505 patients who underwent lumbar fusion surgery. Six distinct machine learning models were formulated: extreme gradient boosting (XGBoost), decision tree (DT), random forest (RF), support vector machine (SVM), Gaussian naive Bayes (GaussianNB), and K-nearest neighbors (KNN) models. Evaluation of model performance on the test dataset was performed using performance metrics, and the analysis was executed through the SHAP framework.

Results.

CSFL was detected in 95 (2.71%) of 3505 patients. Notably, the XGBoost model exhibited outstanding accuracy in forecasting CSFLs, with high precision (0.9815), recall (0.6667), accuracy (0.8182), F1 score (0.7347), and AUC (0.7343). In addition, through SHAP analysis, significant predictors of CSFL were identified, including ligamentum flavum thickness, zygapophysial joint degeneration grade, central spinal stenosis grade, decompression segment count, decompression mode, intervertebral height difference, Cobb angle, intervertebral height index difference, operation mode, lumbar segment lordosis angle difference, Meyerding grade of lumbar spondylolisthesis, and revision surgery.

Conclusions.

The combination of the XGBoost model with the SHAP is an effective tool for predicting the risk of CSFL during lumbar fusion surgery. Its implementation could aid clinicians in making informed decisions, potentially enhancing patient outcomes and lowering healthcare expenses. This study advocates for the adoption of this approach in clinical settings to enhance the evaluation of CSFL risk among patients undergoing lumbar fusion.
Diaphragm-sparing efficacy of subparaneural upper trunk block for arthroscopic shoulder surgery
Authors: Jo Yumin , Oh Chahyun , Lee Woo-Yong , Lee Donggeun , Shin Suyeon , Chung Woosuk , Lim Chaeseong , Lee Sun Yeul , Hong Boohwi
Published: July 2024

BACKGROUND

Inter-scalene block (ISB) is associated with an inevitable risk of hemi-diaphragmatic paresis (HDP). To reduce the risk of HDP, an upper trunk block (UTB) has been proposed at the brachial plexus division level.

OBJECTIVE

We hypothesised that UTB would be associated with a lower incidence of HDP than ISB while providing sufficient analgesia following arthroscopic shoulder surgery.

DESIGN

Randomised controlled trial.

SETTING

A tertiary teaching hospital.

PATIENTS

Seventy patients aged 20 to 80 years undergoing arthroscopic rotator cuff repair.

INTERVENTION

Ultrasound-guided ISB or UTB was performed with 5 ml 0.75% ropivacaine.

MAIN OUTCOME MEASURES

The primary outcome was the incidence of complete HDP, assessed by diaphragm excursion using ultrasound, defined as a decrease to 25% or less of baseline or occurrence of paradoxical movement. Postoperative pulmonary function change, pain scores, opioid consumption and pain-related outcomes were the secondary outcomes.

RESULTS

The UTB group had a significantly lower incidence of complete HDP than the ISB group [5.9% (2/34) vs. 41.7% (15/36); absolute difference, 35.8%; 95% confidence interval (CI), 17.8 to 53.7%; P < 0.001]. The postblockade decline in pulmonary function was more pronounced in the ISB group than that in the UTB group. The pain score at 1 h postoperatively was not significantly different between the groups (ISB vs. UTB group: median 0 vs. 1; median difference, −1; 95% CI, −2 to 0.5). No significant difference was observed in any other secondary outcomes.

CONCLUSION

UTB was associated with a lower incidence of HDP compared with ISB while providing excellent analgesia in arthroscopic shoulder surgery.

TRIAL REGISTRATION

Clinical Trial Registry of Korea (https://cris.nih.go.kr) identifier: KCT0007002.

IRB NUMBER

Chungnam National University Hospital Institutional Review Board No. 2021-12-069.
Contained hepatic vascular injuries following liver trauma: a retrospective monocentric study and review of the literature
Authors: Frey Sébastien , Bentellis Imad , Sedat Jacques , Poirier Florent , Baque Patrick , Massalou Damien
Published: July 2024

Background:

Over the past 30 years, there has been a major shift in the management of liver trauma. Contained hepatic vascular injuries (CHVI), including pseudoaneurysms and arteriovenous fistulas, are often feared because of the risk of secondary hemorrhage. However, little is known about CHVI. There are no guidelines for their management. Our aim was to validate the risk factors for CHVI, to identify the associated morbidities, and to establish a management protocol.

Materials and methods:

A retrospective study of 318 liver trauma cases from a level 1 trauma center over the past 15 years, comparing the presence or absence of CHVI. Univariable and multivariable analyses were conducted. The treatment used to manage CHVI was also compared.

Results:

Liver trauma with the following characteristics, AAST grade ≥III, bilateral injuries, and laceration-type lesions, were associated with a higher risk of CHVI. Grade AAST ≥III and bilateral injuries were confirmed in a multivariable study with odds ratios as high as 4.0 and 3.5, respectively. CHVI was associated with significantly more delayed bleeding and controlled computed tomography. After analyzing the noninterventional management of CHVI less than 2 cm, a management algorithm is proposed.

Conclusions:

This retrospective unicentric study and literature review provide additional insight into the patient profile at risk for developing CHVI, its associated morbidity, and its management.
Intestinal adaptation and rehabilitation in adults with short bowel syndrome
Authors: Pironi Loris
Published: July 2024

Purpose of review

Over the past decade, trophic gastrointestinal hormonal factors have been included in the intestinal rehabilitation programs for short bowel syndrome (SBS). Up today the only trophic factor approved for clinical practice is the glucagon-like peptide-2 (GLP-2) analogue, teduglutide. A literature review on the last 2-year data on GLP-2 analogues for the treatment of SBS in adults has been performed.

Recent findings

Several reports on real-world data on the efficacy and safety of teduglutide treatment for SBS, some case-reports on the use of teduglutide in non-SBS conditions as well as phase 2 trials on new GL-2 analogues on patients with SBS have been retrieved,

Real-world data confirmed the teduglutide efficacy not only in weaning off IVS in accurately selected patients but also increased the alert on the risk of development of gastrointestinal polyps related to the drug; the impact of the therapy on patients’ QoL deserves further studies and the cost-utility of the treatment is still uncertain. Some case reports highlighted the potential benefit of treatment with teduglutide in non-SBS gastrointestinal diseases, such as graft-versus-host disease, primary amyloidosis and refractory microscopic colitis. Phase 2 RCTs on safety and efficacy of two new long-acting GLP-2 analogues, glepaglutide and apraglutide, were published, and phase 3 RCTs have been completed.
Factors associated with hospital revisitation within 7 days among patients discharged at triage: a case–control study
Authors: Ylä-Mattila Jari , Koivistoinen Teemu , Siippainen Henna , Huhtala Heini , Mustajoki Sami
Published: July 2024

Background and importance

Existing data are limited for determining the medical conditions best suited for an emergency department (ED) redirection strategy in a heterogeneous, nonurgent patient population.

Objective

The aim was to establish factors associated with hospital revisits within 7 days among patients discharged or redirected by a triage team.

Design, settings, and participants

An observational single-center case–control study was conducted at the Tampere University Hospital ED for the full calendar year of 2019. The cases comprised unplanned hospital revisits within 7 days of being discharged or redirected by triage, while the controls were discharged or redirected but did not revisit.

Outcome measures and analysis

The primary outcome was an unplanned hospital revisit within 7 days. A subgroup analysis was conducted for revisits leading to hospitalization. Basic demographics, comorbidities before triage, and triage visit characteristics were considered as predictive factors for the revisit. A backward stepwise conditional logistic regression analysis was performed.

Main Results

During the calendar year of 2019, there were a total of 92 406 ED visits. Of these, 7216 (7.8%) visits were discharged or redirected by triage, and 6.5% (n = 467) of all these patients revisited. Of the revisiting patients, 25% (n = 117) were hospitalized. In multivariable analysis, higher age was associated with both revisitation [odds ratio (OR): 1.01, 95% confidence interval (CI): 1.00–1.02] and hospitalization (OR: 1.02, 95% CI: 1.00–1.04). Furthermore, using other visits as a reference, abdominal pain was associated with revisitation and hospitalization (OR: 3.70, 95% CI: 2.24–6.11 and OR: 5.28, 95% CI: 2.08–13.4, respectively).

Conclusion

Higher age and abdominal pain were associated with hospital revisitation and hospitalization within 7 days among patients directly discharged or redirected by the triage team. Regardless of the triage system in use, there might be patient groups that should be evaluated more cautiously if a triage-based discharge or redirection strategy is to be considered.
Effect of melatonin as a therapeutic strategy against intrauterine growth restriction: a mini-review of current state
Authors: Rashidi Seyed Yasin , Rafiyan Mahdi , Asemi Reza , Asemi Zatollah , Mohammadi Sotoudeh
Published: July 2024

Intrauterine growth restriction (IUGR) or intrauterine growth retardation is a condition that the fetus does not grow as expected. And the biometric profile does not match with the age of fetus. This condition is associated with increased mortality and morbidity of the neonates along with increased risk of cardiovascular, lung, and central nervous system damage. Despite close monitoring of high-risk mothers and the development of new therapeutic approaches, the optimal outcome has not been achieved yet that it indicates the importance of investigations on new therapeutic approaches. Melatonin (MLT) is a neurohormone mainly produced by the pineal gland and has a wide range of effects on different organs due to the broad dispersion of its receptors. Moreover, melatonin is produced by the placenta and also its receptors have been found on the surface of this organ. Not only studies showed the importance of this neurohormone on growth and development of fetus but also they proved its highly anti-oxidant properties. As in IUGR the oxidative stress and inflammation increased melatonin could counteract these changes and improved organ’s function. In this study, we found that use of MLT could be a good clinical approach for the treatment of IUGR as its high anti-oxidant activity and vasodilation could dampen the mechanisms lead to the IUGR development.
Diagnostic Value of Combined BCOR, Cyclin D1, and CD10 in Differentiating Endometrial Stromal Sarcoma From Other Uterine Spindle Cell Lesions
Authors: Abouelkhair Mariam B. , Shakweer Marwa M. , Faisal Malames M. , Nasreldin Magda H. , Farid Laila M.
Published: July 2024

Uterine spindle cell lesions share a dilemmatic overlapped features that needed to be addressed by the pathologist to reach a conclusive accurate diagnosis for its prognostic value and different management decisions. Usage of combined IHC panel can be an aiding guiding tool in this context. The aim of this study is to evaluate the diagnostic value of combined BCOR, Cyclin D1, and CD10 IHC panel in differentiating endometrial stromal sarcoma from other uterine spindle cell lesions. This study included 60 cases categorized into endometrial stromal sarcoma group (ESS) (12 cases high-grade endometrial stromal sarcoma [HGESS] and 18 cases low-grade endometrial stromal sarcoma [LGESS]), malignant uterine spindle cell lesions group (5 cases adenosarcoma [AS], 6 cases leiomyosarcoma [LS], 4 cases carcinosarcoma [CS]), and benign uterine lesions group (5 cases endometrial stromal nodule [ESN], 5 cases leiomyoma, and 5 cases adenomyosis). IHC staining procedure and evaluation for BCOR, Cyclin D1, and CD10 was performed on all studied cases. BCOR IHC staining was positive in all HGESS (12/12) of ESS group cases, with diffuse pattern in 75% of cases. BCOR-diffuse staining pattern was not recorded in any of LGESS (0/18), malignant mesenchymal lesions group (0/15), and also benign lesions group (0/15). Cyclin D1 positivity was observed only in HGESS cases, in parallel with positive-BCOR expression. On the contrary, CD10 was negatively expressed in all HGESS and positive in all LGESS, ESN, and adenomyosis cases. A specificity of 100% and sensitivity of 75% were recorded in differentiating HGESS from malignant mesenchymal lesions (including LMS, AS, and CS) and also HGESS from LGESS when using the combined panel BCOR+ve D/Cyclin D1+ve / CD10−ve, considering only the BCOR-diffuse staining pattern. In conclusion, BCOR+ve D/Cyclin D1+ve/CD10−ve as a combined panel is 100% specific and with lesser sensitivity in diagnosing HGESS as well as differentiating it from LGESS and other malignant uterine spindle cell lesions
Inactivation of highly pathogenic avian influenza virus with high temperature short time continuous flow pasteurization and virus detection in bulk milk tanks
Authors: Spackman Erica , Anderson Nathan , Walker Stephen , Suarez David L. , Jones Deana R. , McCoig Amber , Colonius Tristan , Roddy Timothy , Chaplinski Nicholas J.
Published: July 2024

Infections of dairy cattle with clade 2.3.4.4b H5N1 highly pathogenic avian influenza virus (HPAIV) were reported in March 2024 in the U.S. and viable virus was detected at high levels in raw milk from infected cows. This study aimed to determine the potential quantities of infectious HPAIV in raw milk in affected states where herds were confirmed positive by USDA for HPAIV (and therefore were not representative of the entire population), and to confirm that the commonly used continuous flow pasteurization using the FDA approved 72°C (161°F) for 15 s conditions for high temperature short time (HTST) processing, will inactivate the virus. Double-blinded raw milk samples from bulk storage tanks from farms (n=275) were collected in four affected states. Samples were screened for influenza A using quantitative real-time RT-PCR (qrRT-PCR) of which 158 (57.5%) were positive and were subsequently quantified in embryonating chicken eggs. Thirty-nine qrRT-PCR positive samples (24.8%) were positive for infectious virus with a mean titer of 3.5 log1050% egg infectious doses (EID50) per mL. To closely simulate commercial milk pasteurization processing systems, a pilot-scale continuous flow pasteurizer was used to evaluate HPAIV inactivation in artificially contaminated raw milk using the most common legal conditions in the US: 72°C (161°F) for 15s. Among all replicates at two flow rates (n=5 at 0.5L/min; n=4 at 1L/min), no viable virus was detected. A mean reduction of ≥5.8 ± 0.2 log10EID50/mL occurred during the heating phase where the milk is brought to 72.5°C before the holding tube. Estimates from heat-transfer analysis support that standard U.S. continuous flow HTST pasteurization parameters will inactivate >12 log10EID50/mL of HPAIV, which is ~9 log10EID50/mL greater than the mean quantity of infectious virus detected in raw milk from bulk storage tank samples. These findings demonstrate that the milk supply is safe.
PFHpA alters lipid metabolism and increases the risk of metabolic dysfunction-associated steatotic liver disease in youth—a translational research framework
Authors: Baumert Brittney O. , Maretti-Mira Ana C. , Li Zhenjiang , Stratakis Nikos , Zhao Yinqi , Walker Douglas I. , Wang Hongxu , Fischer Fabian Christoph , Jia Qiran , Valvi Damaskini , Bartell Scott M. , Chen Carmen , Inge Thomas , Ryder Justin , Jenkins Todd , Sisley Stephanie , Xanthakos Stavra , Kohli Rohit , Rock Sarah , Eckel Sandrah P. , La Merrill Michele A. , Aung Max M. , Salomon Matthew P. , McConnell Rob , Goodrich Jesse , Conti David V. , Golden-Mason Lucy , Chatzi Lida
Published: July 2024

To address the growing epidemic of liver disease, particularly in pediatric populations, it is crucial to identify modifiable risk factors for the development and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). Per- and polyfluoroalkyl substances (PFAS) are persistent ubiquitous chemicals and have emerged as potential risk factors for liver damage. However, their impact on the etiology and severity of MASLD remains largely unexplored in humans. This study aims to bridge the gap between human and in vitro studies to understand how exposure to perfluoroheptanoic acid (PFHpA), one of the emerging PFAS replacements which accumulates in high concentrations in the liver, contributes to MASLD risk and progression. First, we showed that PFHpA plasma concentrations were significantly associated with increased risk of MASLD in obese adolescents. Further, we examined the impact of PFHpA on hepatic metabolism using 3D human liver spheroids and single-cell transcriptomics to identify major hepatic pathways affected by PFHpA. Next, we integrated thein vivoandin vitromulti-omics datasets with a novel statistical approach which identified signatures of proteins and metabolites associated with MASLD development triggered by PFHpA exposure. In addition to characterizing the contribution of PFHpA to MASLD progression, our study provides a novel strategy to identify individuals at high risk of PFHpA-induced MASLD and develop early intervention strategies. Notably, our analysis revealed that the proteomic signature exhibited a stronger correlation between both PFHpA exposure and MASLD risk compared to the metabolomic signature. While establishing a clear connection between PFHpA exposure and MASLD progression in humans, our study delved into the molecular mechanisms through which PFHpA disrupts liver metabolism. Ourin vitrofindings revealed that PFHpA primarily impacts lipid metabolism, leading to a notable increase of lipid accumulation in human hepatocytes after PFHpA exposure. Among the pathways involved in lipid metabolism in hepatocytes, regulation of lipid metabolism by PPAR-a showed a remarkable activation. Moreover, the translational research framework we developed by integrating human and in vitro data provided us biomarkers to identify individuals at a high risk of MASLD due to PFHpA exposure. Our framework can inform policies on PFAS-induced liver disease and identify potential targets for prevention and treatment strategies.
Immune Checkpoint Inhibition-related Neuroinflammation Disrupts Cognitive Function
Authors: Ifejeokwu Onwodi V. , Do An , El Khatib Sanad M. , Ho Nhu H. , Zavala Angel , Othy Shivashankar , Acharya Munjal M.
Published: July 2024

Combinatorial blockade of Cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and Programmed Cell Death Protein 1 (PD-1) significantly improve the progression-free survival of individuals with metastatic cancers, including melanoma. In addition to unleashing anti-tumor immunity, combination immune checkpoint inhibition (ICI) disrupts immune-regulatory networks critical for maintaining homeostasis in various tissues, including the central nervous system (CNS). Although ICI- and cancer-related cognitive impairments (CRCI) in survivors are increasingly becoming evident, our understanding of ICI-induced immune-related adverse effects (IREA) in the CNS remains incomplete. Here, our murine melanoma model reveals that combination ICI impairs hippocampal-dependent learning and memory, as well as memory consolidation processes. Mechanistically, combination ICI disrupted synaptic integrity, and neuronal plasticity, reduced myelin, and further predisposed CNS for exaggerated experimental autoimmune encephalomyelitis. Combination ICI substantially altered both lymphoid and myeloid cells in the CNS. Neurogenesis was unaffected, however, microglial activation persisted for two-months post- ICI, concurrently with cognitive deficits, which parallels clinical observations in survivors. Overall, our results demonstrate that blockade of CTLA-4 and PD-1 alters neuro-immune homeostasis and activates microglia, promoting long-term neurodegeneration and driving cognitive impairments. Therefore, limiting microglial activation is a potential avenue to mitigate CNS IRAE while maintaining the therapeutic benefits of rapidly evolving ICIs and their combinations.

SIGNIFICANCE

Despite the superior therapeutic efficacy of immune checkpoint inhibition (ICI) for cancers, its undesired effects on brain function are not fully understood. Here, we demonstrate that combination ICI elevates neuroinflammation, activates microglia, leading to detrimental neurodegenerative and neurocognitive sequelae.