bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fetal Exposure to Tobacco Metabolites and Depression During Adulthood: Beyond Binary Measures
Authors: Shenassa Edmond D. , Gleason Jessica L. , Hirabayashi Kathryn 
Published: July 2024

Background:
Sibling studies of maternal smoking during pregnancy and subsequent risk of depression have produced mixed results. A recent study identified not considering the amount of maternal smoking and age of onset as potentially masking a true association. We examine these issues and also the amount of maternal smoking during pregnancy as a determinant of the severity of depressive symptoms.

Methods:
We analyzed data from the community-based National Longitudinal Survey of Youth (US, 1994–2016). Mothers reported smoking during pregnancy (none, <1 pack/day, ≥1 pack/day). We assessed offspring’s lifetime depression (i.e., ≥8 symptoms) and symptom counts with the Centers for Epidemiologic Studies Depression scale. We estimated the risk of these two outcomes in the full sample (n = 7172) and among siblings (n = 6145) using generalized linear mixed-effects models with random intercepts by family and family-averaged means for sibling analyses.

Results:
Among siblings, we observed dose-dependent elevations for both risk of depression (smoking during pregnancy <1 pack/day adjusted risk ratio [aRR] = 1.18; 95% confidence interval [CI] = 1.07, 1.30; smoking ≥1 aRR = 1.36; 95% CI = 1.19, 1.56) and severity of depressive symptoms (smoking <1 pack/day aRR = 1.12; 95% CI = 1.08, 1.16); smoking ≥1 pack/day aRR = 1.25; 95% CI = 1.18, 1.31). Among both samples, the P for trend was <0.01. In analysis limited to offspring diagnosed before age 18, results for severity were attenuated.

Conclusions:
This evidence supports the existence of an independent association between maternal smoking during pregnancy and both the risk of depression and the severity of depressive symptoms. The results highlight the utility of considering the amount of smoking, severity of symptoms, and age of onset.
The impact of surging transplantation of alcohol-associated liver disease on transplantation for HCC and other indications
Authors: Ayyala-Somayajula Divya , Dodge Jennifer L. , Zhou Kali , Terrault Norah A. , Yuan Liyun 
Published: July 2024

Background:
Liver transplantation (LT) for alcohol-associated liver disease (ALD) is increasing and may impact LT outcomes for patients listed for HCC and other indications.

Methods:
Using US adults listed for primary LT (grouped as ALD, HCC, and other) from October 8, 2015, to December 31, 2021, we examined the impact of center-level ALD LT volume (ATxV) on waitlist outcomes in 2 eras: Era 1 (6-month wait for HCC) and Era 2 (MMaT-3). The tertile distribution of ATxV (low to high) was derived from the listed candidates as Tertile 1 (T1): <28.4%, Tertile 2 (T2): 28.4%–37.6%, and Tertile 3 (T3): >37.6% ALD LTs per year. Cumulative incidence of waitlist death and LT within 18 months from listing by LT indication were compared using the Gray test, stratified on eras and ATxV tertiles. Multivariable competing risk regression estimated the adjusted subhazard ratios (sHRs) for the risk of waitlist mortality and LT with interaction effects of ATxV by LT indication (interaction p).

Results:
Of 56,596 candidates listed, the cumulative waitlist mortality for those with HCC and other was higher and their LT probability was lower in high (T3) ATxV centers, compared to low (T1) ATxV centers in Era 2. However, compared to ALD (sHR: 0.92 [0.66–1.26]), the adjusted waitlist mortality for HCC (sHR: 1.15 [0.96–1.38], interaction p = 0.22) and other (sHR: 1.13 [0.87–1.46], interaction p = 0.16) were no different suggesting no differential impact of ATxV on the waitlist mortality. The adjusted LT probability for HCC (sHR: 0.89 [0.72–1.11], interaction p = 0.08) did not differ by AtxV while it was lower for other (sHR: 0.82 [0.67–1.01], interaction p = 0.02) compared to ALD (sHR: 1.04 [0.80–1.34]) suggesting a differential impact of ATxV on LT probability.

Conclusions:
The high volume of LT for ALD does not impact waitlist mortality for HCC and others but affects LT probability for other in the MMAT-3 era warranting continued monitoring.
NUAK1 promotes metabolic dysfunction-associated steatohepatitis progression by activating Caspase 6–driven pyroptosis and inflammation
Authors: Sheng Mingwei , Huo Shuhan , Jia Lili , Weng Yiqi , Liu Weihua , Lin Yuanbang , Yu Wenli 
Published: July 2024

Background:
lNUAK1 is strongly associated with organ fibrosis, but its causal mechanism for modulating lipid metabolism and hepatic inflammation underlying MASH has not been fully clarified.

Method:
In our study, human liver tissues from patients with MASH and control subjects were obtained to evaluate NUAK1 expression. MASH models were established using C57BL/6 mice. Liver damage and molecular mechanisms of the NUAK1-Caspase 6 signaling were tested in vivo and in vitro.

Results:
In the clinical arm, NUAK1 expression was upregulated in liver samples from patients with MASH. Moreover, increased NUAK1 was detected in mouse MASH models. NUAK1 inhibition ameliorated steatohepatitis development in MASH mice accompanied by the downregulation of hepatic steatosis and fibrosis. Intriguingly, NUAK1 was found to facilitate Caspase 6 activation and trigger pyroptosis in MASH-stressed livers. Disruption of hepatocytes Caspase 6 decreased MASH-induced liver inflammation with upregulated TAK1 but diminished RIPK1. Moreover, we found that NUAK1/Caspase 6 axis inhibition could accelerate the interaction between TAK1 and RIPK1, which in turn led to the degradation of RIPK1.

Conclusions:
In summary, our study elucidates that NUAK1-Caspase 6 signaling controls inflammation activation in MASH through the interaction between TAK1 and RIPK1, which is crucial for controlling pyroptosis and promoting the progression of MASH.
Loss of β-catenin reveals a role for glutathione in regulating oxidative stress during cholestatic liver disease
Authors: Balogun Oluwashanu , Shao Daniel , Carson Matthew , King Thalia , Kosar Karis , Zhang Rong , Zeng Gang , Cornuet Pamela , Goel Chhavi , Lee Elizabeth , Patel Garima , Brooks Eva , Monga Satdarshan P. , Liu Silvia , Nejak-Bowen Kari 
Published: July 2024

Background:
Cholestasis is an intractable liver disorder that results from impaired bile flow. We have previously shown that the Wnt/β-catenin signaling pathway regulates the progression of cholestatic liver disease through multiple mechanisms, including bile acid metabolism and hepatocyte proliferation. To further explore the impact of these functions during intrahepatic cholestasis, we exposed mice to a xenobiotic that causes selective biliary injury.

Methods:
α-naphthylisothiocyanate (ANIT) was administered to liver-specific knockout (KO) of β-catenin and wild-type mice in the diet. Mice were killed at 6 or 14 days to assess the severity of cholestatic liver disease, measure the expression of target genes, and perform biochemical analyses.

Results:
We found that the presence of β-catenin was protective against ANIT, as KO mice had a significantly lower survival rate than wild-type mice. Although serum markers of liver damage and total bile acid levels were similar between KO and wild-type mice, the KO had minor histological abnormalities, such as sinusoidal dilatation, concentric fibrosis around ducts, and decreased inflammation. Notably, both total glutathione levels and expression of glutathione-S-transferases, which catalyze the conjugation of ANIT to glutathione, were significantly decreased in KO after ANIT. Nuclear factor erythroid-derived 2-like 2, a master regulator of the antioxidant response, was activated in KO after ANIT as well as in a subset of patients with primary sclerosing cholangitis lacking activated β-catenin. Despite the activation of nuclear factor erythroid-derived 2-like 2, KO livers had increased lipid peroxidation and cell death, which likely contributed to mortality.

Conclusions:
Loss of β-catenin leads to increased cellular injury and cell death during cholestasis through failure to neutralize oxidative stress, which may contribute to the pathology of this disease.
Clinical and genetic risk factors for progressive fibrosis in metabolic dysfunction–associated steatotic liver disease
Authors: Kaplan David E. , Teerlink Craig C. , Schwantes-An Tae-Hwi , Norden-Krichmar Trina M. , DuVall Scott L. , Morgan Timothy R. , Tsao Philip S. , Voight Benjamin F. , Lynch Julie A. , Vujković Marijana , Chang Kyong-Mi 
Published: July 2024

Background:
Fibrosis-4 (FIB4) is a recommended noninvasive test to assess hepatic fibrosis among patients with metabolic dysfunction–associated steatotic liver disease (MASLD). Here, we used FIB4 trajectory over time (ie, “slope” of FIB4) as a surrogate marker of liver fibrosis progression and examined if FIB4 slope is associated with clinical and genetic factors among individuals with clinically defined MASLD within the Million Veteran Program Cohort.

Methods:
In this retrospective cohort study, FIB4 slopes were estimated through linear regression for participants with clinically defined MASLD and FIB4 <2.67 at baseline. FIB4 slope was correlated with demographic parameters and clinical outcomes using logistic regression and Cox proportional hazard models. FIB4 slope as a quantitative phenotype was used in a genome-wide association analysis in ancestry-specific analysis and multiancestry meta-analysis using METAL.

Results:
FIB4 slopes, generated from 98,361 subjects with MASLD (16,045 African, 74,320 European, and 7996 Hispanic), showed significant associations with sex, ancestry, and cardiometabolic risk factors (p < 0.05). FIB4 slopes also correlated strongly with hepatic outcomes and were independently associated with time to cirrhosis. Five genetic loci showed genome-wide significant associations (p < 5 × 10−8) with FIB4 slope among European ancestry subjects, including 2 known (PNPLA3 and TM6SF2) and 3 novel loci (TERT 5.1 × 10−11; LINC01088, 3.9 × 10−8; and MRC1, 2.9 × 10−9).

Conclusions:
Linear trajectories of FIB4 correlated significantly with time to progression to cirrhosis, with liver-related outcomes among individuals with MASLD and with known and novel genetic loci. FIB4 slope may be useful as a surrogate measure of fibrosis progression.
MULTIMODAL IMAGING OF DIDANOSINE-RELATED RETINOPATHY
Authors: Alexander João Gabriel , Samico Gustavo Albrecht , Ribeiro Lucas Zago , Vasconcelos Júnior Huber Martins 
Published: July 2024

Purpose:
To describe multimodal imaging findings in a rare case of didanosine-related retinopathy.

Methods:
Case report.

Results:
55-year-old male patient presenting peripheral visual loss and nyctalopia for the last 8 years in both eyes. Previous medical history of HIV, and use of didanosine for almost 10 years. Fundus examination, autofluorescence, and optical coherence tomography showed bilateral symmetrical peripheral chorioretinal atrophy, sparing the posterior pole. Genetic testing was performed to exclude inherited retinopathies.

Conclusion:
DDI-related chorioretinal toxicity is a rare disease, with few reports in the literature. Multimodal imaging and genetic testing were essential for precise diagnosis. The limitation of this report includes the late presentation of the patient to our clinic, making the evaluation difficult to determine early signs of toxicity and to determine the precise length of DDI treatment and whether or not the degeneration progressed shortly after cessation of the medication.
Intensity, Characteristics, and Factors Associated With Receipt of Care Coordination Among High-Risk Veterans in the Veterans Health Administration
Authors: Govier Diana J. , Hickok Alex , Niederhausen Meike , Rowneki Mazhgan , McCready Holly , Mace Elizabeth , McDonald Kathryn M. , Perla Lisa , Hynes Denise M. 
Published: July 2024

Background:
The Veterans Health Administration (VHA) has initiatives underway to enhance the provision of care coordination (CC), particularly among high-risk Veterans. Yet, evidence detailing the characteristics of and who receives VHA CC is limited.

Objectives:
We examined intensity, timing, setting, and factors associated with VHA CC among high-risk Veterans.

Research Design:
We conducted a retrospective observational cohort study, following Veterans for 1 year after being identified as high-risk for hospitalization or mortality, to characterize their CC. Demographic and clinical factors predictive of CC were identified via multivariate logistic regression.

Subjects:
A total of 1,843,272 VHA-enrolled high-risk Veterans in fiscal years 2019-2021.

Measures:
We measured 5 CC variables during the year after Veterans were identified as high risk: (1) receipt of any service, (2) number of services received, (3) number of days to first service, (4) number of days between services, and (5) type of visit during which services were received.

Results:
Overall, 31% of high-risk Veterans in the sample received CC during one-year follow-up. Among Veterans who received ≥1 service, a median of 2 [IQR (1, 6)] services were received. Among Veterans who received ≥2 services, there was a median of 26 [IQR (10, 57)] days between services. Most services were received during outpatient psychiatry (46%) or medicine (16%) visits. Veterans’ sociodemographic and clinical characteristics were associated with receipt of CC.

Conclusions:
A minority of Veterans received CC in the year after being identified as high-risk, and there was variation in intensity, timing, and setting of CC. Research is needed to examine the fit between Veterans’ CC needs and preferences and VHA CC delivery.
Familial Hemophagocytic Lymphohistiocytosis Screening in Neonatal Sepsis
Authors: Kadi Ozan Zuhre , Erduran Erol , Ceylaner Serdar , Aslan Yakup , Bahadir Aysenur , Reis Gokce P. , Mutlu Mehmet 
Published: July 2024

Objective:
Neonatal sepsis and familial hemophagocytic lymphohistiocytosis (fHLH) have similar clinical and laboratory symptoms and the possibility of overlooking fHLH diagnosis is high in newborns with sepsis. History of consanguineous marriage and/or sibling death, hepatomegaly/splenomegaly, and hyperferritinemia (>500 ng/mL) are likely to support fHLH in newborns with sepsis. Therefore, in newborns with sepsis in whom at least 2 out of these 3 criteria were detected, genetic variants was investigated for the definitive diagnosed of fHLH. According to the results of genetic examination, we investigated whether these criteria supporting fHLH could be used as a screening test in fHLH.

Materials and Methods:
fHLH-associated genetic variants were investigated in 22 patients diagnosed with neonatal sepsis who fulfilled at least 2 out of the following criteria (1) history of consanguineous marriage and/or sibling death, (2) hepatomegaly/splenomegaly, and (3) hyperferritinemia (>500 ng/mL)

Results:
Heterozygous variants were determined in 6 patients (27.2%): 3 STXBP2, 1 STX11, 1 UNC13D, and 1 PRF1. Polymorphisms associated with the clinical symptoms and signs of HLH were determined in 5 patients (22.7%): 4 UNC13D, 1 PRF1. Two patients were in the heterozygous variants and polymorphism associated with the clinical symptoms and signs of HLH groups. In 12 patients, benign polymorphisms were detected in STXBP2 and UNC13D genes. No change in fHLH associated genes were found in 1 patient.

Conclusion:
Some variants and/or polymorphisms identified in our patients have been previously reported in patients with HLH. Therefore, we recommend further investigation of fHLH in patients with neonatal sepsis who fulfill at least 2 out of the above 3 criteria.
Automatic Segmentation of Heschl Gyrus and Planum Temporale by MRICloud
Authors: Perez-Heydrich Carlos A. , Padova Dominic , Kutten Kwame , Ceritoglu Can , Faria Andreia , Ratnanather J. Tilak , Agrawal Yuri 
Published: July 2024

Objectives:
This study used a cloud-based program, MRICloud, which parcellates T1 MRI brain scans using a probabilistic classification based on manually labeled multi-atlas, to create a tool to segment Heschl gyrus (HG) and the planum temporale (PT).

Methods:
MRICloud is an online platform that can automatically segment structural MRIs into 287 labeled brain regions. A 31-brain multi-atlas was manually resegmented to include tags for the HG and PT. This modified atlas set with additional manually labeled regions of interest acted as a new multi-atlas set and was uploaded to MRICloud. This new method of automated segmentation of HG and PT was then compared to manual segmentation of HG and PT in MRIs of 10 healthy adults using Dice similarity coefficient (DSC), Hausdorff distance (HD), and intraclass correlation coefficient (ICC).

Results:
This multi-atlas set was uploaded to MRICloud for public use. When compared to reference manual segmentations of the HG and PT, there was an average DSC for HG and PT of 0.62 ± 0.07, HD of 8.10 ± 3.47 mm, and an ICC for these regions of 0.83 (0.68–0.91), consistent with an appropriate automatic segmentation accuracy.

Conclusion:
This multi-atlas can alleviate the manual segmentation effort and the difficulty in choosing an HG and PT anatomical definition. This protocol is limited by the morphology of the MRI scans needed to make the MRICloud atlas set. Future work will apply this multi-atlas to observe MRI changes in hearing-associated disorders.
How to Disclose Internal Carotid Artery Dehiscence in Patients With Eustachian Tube Dysfunction: Cone Beam Computed Tomography or High-resolution Computed Tomography?
Authors: Holm Niels Højvang , Molnár Balázs , Ovesen Therese 
Published: July 2024

Objective:
To compare the prevalence of internal carotid artery dehiscence (ICAD) on high-resolution computed tomography (HRCT) and cone beam computed tomography (CBCT) in patients with Eustachian tube dysfunction (ETD).

Study Design:
A prospective, cohort study.

Setting:
The outpatient clinic at the Department of Otorhinolaryngology, Head and Neck Surgery at Gødstrup Hospital, Denmark (tertiary referral center).

Patients:
Patients >18 years of age diagnosed with long-standing ETD undergoing HRCT and/or CBCT prior to balloon Eustachian tuboplasty.

Intervention(s):
Patients had either initially HRCT and later CBCT performed (HRCT + CBCT group) or solely CBCT (CBCT group).

Main Outcome Measure(s):
Prevalence of ICAD assessed with HRCT and CBCT.

Results:
A total of 23 patients were included in the HRCT + CBCT group and 36 patients in the CBCT group. In the HRCT + CBCT group, ICAD was found in 13 temporal bones (28.3%) with HRCT and 7 temporal bones (15.2%) with CBCT (P = 0.0003). No new cases of ICAD were found with CBCT. In the CBCT group, ICAD was found in 6 temporal bones (8.3%). In both HRCT and CBCT, patients suffered from ETD in 61.5% of the ears where ICAD was found.

Conclusions:
CBCT has a higher specificity than HRCT in diagnosing ICAD in patients with ETD while at the same time using less radiation.
18F-THK5351 Uptake May Not Estimate Neurofibrillary Tangles in In Vivo Images
Authors: Ishibashi Kenji , Tago Tetsuro , Kameyama Masashi , Toyohara Jun , Ishii Kenji 
Published: July 2024

Abstract
Currently, monoamine oxidase B is recognized as the primary target of 18F-THK5351, although 18F-THK5351 was initially developed to target neurofibrillary tangles (NFTs) in Alzheimer disease. When clinically applying 18F-THK5351 PET to visualize ongoing astrogliosis via estimating monoamine oxidase B levels, a crucial concern is how much degree 18F-THK5351 uptake reflects NFTs in in vivo images. To unravel this concern, a head-to-head comparison between 18F-THK5351 and 18F-MK-6240 (estimating NFT) images in the NFT lesion ideally without accompanying astrogliosis is essential. Here, we present such a case suggesting that 18F-THK5351 uptake may not estimate NFTs in in vivo images.
Active trachoma among children aged 1-9 years in Ethiopia: A meta-analysis from 2019 to 2024
Authors: Abore Kibruyisfaw Weldeab , Asebot Melat Tesfaye , Kebede Gifty Birhanemeskel , Khasay Robel Tibebu , Akuma Asonya Abera , Dagne Mahlet Minwuyelet , Tesfaye Tewobesta Fesseha , Abebe Mahlet Tesfaye , Fole Estifanos Bekele 
Published: July 2024

AbstractBackgroundTrachoma is a leading infectious cause of blindness and of significant public health concern targeted for elimination. This study aimed to systematically summarize the magnitude of active trachoma among children aged 1-9 in Ethiopia from 2019-2024MethodsDatabase searches were conducted on Google Scholar, SCOPUS, PubMed, EMBASE, and AJOL for studies published between January 2019 to 31-March-2024 and with restriction to articles published only in English. Data extraction was done using a pre-prepared Excel sheet. STATA version 17 was used to perform the analysis. Heterogeneity between studies was assessed using I2statistics and Cochrane Q. Qualitative synthesis was done to summarize the studies and random effect model was used to estimate the Pooled magnitude of active trachoma with a corresponding 95% confidence interval.ResultA total of 17 studies with 19793 subjects were included in the meta-analysis. The pooled magnitude of active trachoma among children aged 1-9 years was found to be 18.4% (95% CI: 13.88, 22.91). We found a statistically significant heterogeneity between studies. Among the regions, Southwest region was found to have the highest magnitude (44.1%) (95%CI: 41.8%, 46.4%) and Dire Dawa was found to have the lowest (4.3%) (95%CI: 2.9%, 5.7%).ConclusionThe magnitude of active trachoma is higher than the WHO target for elimination. There was significant interregional difference in magnitude of active trachoma. Strengthening SAFE strategy and health education and promotion is recommended.
Plasma membrane folding enables constant surface area-to-volume ratio in growing mammalian cells
Authors: Wu Weida , Lam Alice R. , Suarez Kayla , Smith Grace N. , Duquette Sarah M. , Yu Jiaquan , Mankus David , Bisher Margaret , Lytton-Jean Abigail , Manalis Scott R. , Miettinen Teemu P. 
Published: July 2024

ABSTRACTAll cells are subject to geometric constraints, including the surface area-to-volume (SA/V) ratio, which can limit nutrient uptake, maximum cell size, and cell shape changes. Like the SA/V ratio of a sphere, it is generally assumed that the SA/V ratio of cells decreases as cell size increases. However, the structural complexity of the plasma membrane makes studies of the surface area challenging in cells that lack a cell wall. Here, we investigate near-spherical mammalian cells using single-cell measurements of cell mass and plasma membrane proteins and lipids, which allows us to examine the cell size scaling of cell surface components as a proxy for the SA/V ratio. Surprisingly, in various proliferating cell lines, cell surface components scale proportionally with cell size, indicating a nearly constant SA/V ratio as cells grow larger. This behavior is largely independent of the cell cycle stage and is also observed in quiescent cells, including primary human monocytes. Moreover, the constant SA/V ratio persists when cell size increases excessively during polyploidization. This is enabled by increased plasma membrane folding in larger cells, as verified by electron microscopy. We also observe that specific cell surface proteins and cholesterol can deviate from the proportional size scaling. Overall, maintaining a constant SA/V ratio ensures sufficient plasma membrane area for critical functions such as cell division, nutrient uptake, growth, and deformation across a wide range of cell sizes.