bluuebunny/crossref_metadata_2025_split huggingface dataset:
Elevated Plasma Interleukin-18 Identifies High-Risk Acute Respiratory Distress Syndrome Patients not Distinguished by Prior Latent Class Analyses Using Traditional Inflammatory Cytokines: A Retrospective Analysis of Two Randomized Clinical Trials
Authors: Moore Andrew R. , Pienkos Shaun M. , Sinha Pratik , Guan Jiazhen , O’Kane Cecilia M. , Levitt Joseph E. , Wilson Jennifer G. , Shankar-Hari Manu , Matthay Michael A. , Calfee Carolyn S. , Baron Rebecca M. , McAuley Daniel F. , Rogers Angela J. 
Published: September 2023

OBJECTIVES:
Interleukin-18 (IL-18) plasma level and latent class analysis (LCA) have separately been shown to predict prognosis and treatment response in acute respiratory distress syndrome (ARDS). IL-18 is a measure of inflammasome activation, a pathway potentially distinct from inflammation captured by biomarkers defining previously published LCA classes. We hypothesized that elevated IL-18 would identify distinct “high-risk” patients not captured by prior LCA classifications.

DESIGN:
Statins for acutely injured lungs from sepsis (SAILS) and hydroxymethylglutaryl-CoA reductase inhibition with simvastatin in acute lung injury to reduce pulmonary dysfunction trial (HARP-2) are two large randomized, controlled trials in ARDS in which both LCA assignments and IL-18 levels were shown to predict mortality. We first evaluated the overlap between high IL-18 levels (≥ 800 pg/mL) with prior LCA class assignments using McNemar’s test and then tested the correlation between IL-18 and LCA biomarkers using Pearson’s exact test on log-2 transformed values. Our primary analysis was the association of IL-18 level with 60-day mortality in the hypoinflammatory LCA class, which was assessed using the Fisher exact test and Cox proportional hazards modeling adjusting for age, Acute Physiology and Chronic Health Evaluation score, and gender. Secondary analyses included the association of IL-18 and LCA with mortality within each IL-18/LCA subgroup.

SETTING:
Secondary analysis of two multicenter, randomized controlled clinical trials of ARDS patients.

SUBJECTS:
Six hundred eighty-three patients in SAILS and 511 patients in HARP-2.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
We found that 33% of patients in SAILS and HARP-2 were discordant by IL-18 level and LCA class. We further found that IL-18 level was only modestly correlated (0.17–0.47) with cytokines used in the LCA assignment. A substantial subset of individuals classified as hypoinflammatory by LCA (14% of SAILS and 43% of HARP-2) were classified as high risk by elevated IL-18. These individuals were at high risk for mortality in both SAILS (42% 60-d mortality, odds ratio [OR] 3.3; 95% CI, 1.8–6.1; p < 0.001) and HARP-2 (27% 60-d mortality, OR 2.1; 95% CI, 1.2–3.8; p = 0.009).

CONCLUSIONS:
Plasma IL-18 level provides important additional prognostic information to LCA subphenotypes defined largely by traditional inflammatory biomarkers in two large ARDS cohorts.
MACULAR CHORIORETINAL ATROPHY AND VISUAL OUTCOMES IN RANIBIZUMAB- OR AFLIBERCEPT-TREATED MYOPIC CHOROIDAL NEOVASCULARIZATION
Authors: Kawashima Yu , Hata Masayuki , Miyake Masahiro , Kusaka Mami , Oishi Akio , Ooto Sotaro , Tamura Hiroshi , MIYATA Manabu , Uji Akihito , Ueda-Arakawa Naoko , Takahashi Ayako , Tsujikawa Akitaka 
Published: September 2023

Abstract

Purpose:
To investigate the predictors of macular chorioretinal atrophy (CRA), consisting of patchy atrophy (PA) at the macula and choroidal neovascularization (CNV)-related macular atrophy (CNV-MA), during treatment with either ranibizumab or aflibercept for myopic CNV (mCNV) and its impact on visual outcomes.

Methods:
This retrospective study included 82 eyes with treatment-naïve mCNV who were treated with pro re nata injections of either ranibizumab or aflibercept.

Results:
Nine eyes (11.0%) presented with macular PA at baseline (PA group), and 73 eyes (89.0%) did not (non-PA group). VA improved during the first year in the non-PA group; a similar trend was noted in the PA group until 3 months after initial treatment. This improvement was maintained until 24 months (P<0.001) in the non-PA group, but not in the PA group. In the PA group, macular CRA progressed faster (P<0.0001), and CNV-MA was more frequent during the 2 years of treatments (P=0.04). Even non-PA group eyes sometimes developed CNV-MA (42% at month 24) if they had a larger CNV and thinner subfoveal CT at baseline, resulting in poorer visual prognosis (P<0.01).

Conclusion:
Macular PA at baseline was a risk factor for CNV-MA development and was associated with poor visual outcomes.
Genetic Factors and Characteristics on Spectral-Domain Optical Coherence Tomography Are Associated to Choroidal Thickness in ABCA4-Related Retinopathy Factors of Choroidal Thickness in ABCA4 Retinopathy
Authors: Wang Yimin , Chen Jieqiong , Zhang Min , Yu Suqin , Gong Yuanyuan , Lin Feng , Wu Yidong , Liu Wenjia , Sun Junran , Li Tong , Sun Xiaodong ,   Shanghai Inherited Retinal Disease (SHIRD) Study Group
Published: September 2023

Abstract

Purpose:
To investigate the possible correlation factors of choroidal thickness in ABCA4-related retinopathy.

Methods:
A total of 66 patients were included in the cohort. It is a retrospective, cross-sectional laboratory investigation. The patients were tested using whole exon sequencing (WES) and ophthalmic exams, including slip lamp exams, best corrected visual acuity (BCVA), spectral-domain optical coherence tomography (SD-OCT), fundus photo (FP), and fundus autofluorescence (FAF).

Results:
Besides demographic characteristics (age, onset age, duration), we selected genetic factors and ocular characteristics on SD-OCT as the candidates related to choroidal thickness (CT). Mutation type (inframe mutation or premature termination codon), epiretinal membrane (ERM), RPE- Bruch’s membrane (BM) integrity and macular curvature changes were identified as related factors to choroidal thickness in ABCA4-related retinopathy after the adjustment of Logistic LASSO regression .

Conclusions:
Mutation type, ERM, RPE-BM integrity and macular curvature changes are related factors to choroidal thinning. These findings could provide us a further understanding for the pathological process and clinical features of ABCA4 mutation.
Monocyte to lymphocyte ratio and hemoglobin level to predict tuberculosis after antiretroviral therapy initiation
Authors: Gatechompol Sivaporn , Kerr Stephen J. , Cardoso Sandra W. , Samaneka Wadzanai , Tripathy Srikanth , Godbole Sheela , Ghate Manisha , Kanyama Cecilia , Nyirenda Mulinda , Sugandhavesa Patcharaphan , Machado Andre , Van Leth Frank , Campbell Thomas B. , Swindlells Susan , Avihingsanon Anchalee , Cobelens Frank 
Published: September 2023

Objective:
To determine the performance of the baseline monocyte to lymphocyte ratio (MLR), baseline anemia severity and combination of these biomarkers, to predict tuberculosis (TB) incidence in people with HIV (PWH) after antiretroviral therapy (ART) initiation.

Design:
Multicenter, retrospective cohort study.

Methods:
We utilized the data from study A5175 (Prospective Evaluation of Antiretroviral Therapy in Resource-limited Settings: PEARLS). We assessed the utility of MLR, anemia severity and in combination, for predicting TB in the first year after ART. Cox regression was used to assess associations of MLR and anemia with incident TB. Harrell's C index was used to describe single model discrimination.

Results:
A total of 1455 participants with a median age of 34 [interquartile range (IQR) 29, 41] were included. Fifty-four participants were diagnosed with TB. The hazard ratio (HR) for incident TB was 1.77 [95% confidence interval (CI) 1.01–3.07]; P = 0.04 for those with MLR ≥0.23. The HR for mild/mod anemia was 3.35 (95% CI 1.78–6.29; P < 0.001) and 18.16 (95% CI 5.17–63.77; P < 0.001) for severe anemia. After combining parameters, there were increases in adjusted HR (aHR) for MLR ≥0.23 to 1.83 (95% CI 1.05–3.18), and degrees of anemia to 3.38 (95% CI 1.80–6.35) for mild/mod anemia and 19.09 (95% CI 5.43–67.12) for severe anemia.

Conclusions:
MLR and hemoglobin levels which are available in routine HIV care can be used at ART initiation for identifying patients at high risk of developing TB disease to guide diagnostic and management decisions.
The Surgical Treatment of Tuberous Breast Deformity
Authors: El Israwi Daniel , Makdessi Jean Paul , Bassilios Habre Samer 
Published: September 2023

Abstract
Tuberous breast is a common congenital deformity that might present as unilateral or bilateral breast base constriction, asymmetry, areolar herniation, hypoplasia, ptosis, and skin deficiency. Patients might present with one or more of the mentioned features, rendering a consensus about the optimal surgical technique to correct this deformity nonexistent. In our review article, we present the most common classifications of a tuberous breast, in addition to several surgical approaches that attempt to treat this deformity.
Wormian Bones: Prevalence, Topography, and Implications
Authors: Singh Rajani 
Published: September 2023

Background:
Wormian bones also known as sutural bones are asymmetrical and shapeless bones occurring in cranial sutures and fontanelle of the skull. Their incidence is reported to vary in population. The exact etiology is debatable, but their formation is under the control of both genetic and environmental factors and has great anthropological and clinical implications related to the cranium. Due to high clinical relevance of Wormian bones, the study was carried out. The aim of the study is to expound the incidence and topography of Wormian bones along with clinical significance in dry adult skulls of Indian origin.

Methods:
The study was conducted in the Department of Anatomy using 200 complete adult dry skulls of unknown age and sex. All the sutures in the skull were inspected for the presence of Wormian bones. The Wormian bones were classified into 10 categories, and associated implications were brought out. The Wormian bones were photographed, and details were compared with the available literature.

Results:
The Wormian bones were observed in 190 (380 sides) skulls with 186 on the right side and 108 on the left side. The predominance site of sutural bone was lambdoid suture followed by sagittal suture. The least common site of Wormian bone was lambda.

Conclusion:
The detailed information of precise topography, frequency, and number of Wormian bones is of utmost use for surgeons performing surgery on the skull, anthropologists for identifying races, and forensic scientists for investigating child abuse cases.
SEPSIS LEADS TO IMPAIRED MITOCHONDRIAL CALCIUM UPTAKE AND SKELETAL MUSCLE WEAKNESS BY REDUCING THE MICU1:MCU PROTEIN RATIO
Authors: Li Xuexin , Sun Bowen , Li Jie , Ye Wanlin , Li Mingjuan , Guan Fasheng , Wu Songlin , Luo Xuerong , Feng Jianguo , Jia Jing , Liu Xueru , Li Tao , Liu Li 
Published: September 2023

ABSTRACT

Purpose: Intensive care unit–acquired weakness (ICUAW) is a severe neuromuscular complication that frequently occurs in patients with sepsis. The precise molecular pathophysiology of mitochondrial calcium uptake 1 (MICU1) and mitochondrial calcium uniporter (MCU) in ICUAW has not been fully elucidated. Here, we speculate that ICUAW is associated with MICU1:MCU protein ratio–mediated mitochondrial calcium ([Ca2+]m) uptake dysfunction. Methods: Cecal ligation and perforation (CLP) was performed on C57BL/6J mice to induce sepsis. Sham-operated animals were used as controls. Lipopolysaccharide (LPS) (5 μg/mL) was used to induce inflammation in differentiated C2C12 myoblasts. Compound muscle action potential (CMAP) was detected using a biological signal acquisition system. Grip strength was measured using a grip-strength meter. Skeletal muscle inflammatory factors were detected using ELISA kits. The cross-sectional area (CSA) of the tibialis anterior (TA) muscle was detected by hematoxylin and eosin staining. Cytosolic calcium ([Ca2+]c) levels were measured using Fluo-4 AM. Adeno-associated virus (AAV) was injected into TA muscles for 4 weeks to overexpress MICU1 prophylactically. A lentivirus was used to infect C2C12 cells to increase MICU1 expression prophylactically. Findings: The results suggest that sepsis induces [Ca2+]m uptake disorder by reducing the MICU1:MCU protein ratio, resulting in skeletal muscle weakness and muscle fiber atrophy. However, MICU1 prophylactic overexpression reversed these effects by increasing the MICU1:MCU protein ratio. Conclusions: ICUAW is associated with impaired [Ca2+]m uptake caused by a decreased MICU1:MCU protein ratio. MICU1 overexpression improves sepsis-induced skeletal muscle weakness and atrophy by ameliorating the [Ca2+]m uptake disorder.
Nobiletin ameliorates heatstroke-induced acute lung injury by inhibiting ferroptosis via p53/SLC7A11 pathway
Authors: Chen Hui , Xie Weidang , Peng Zanling , Liu Yanan , Li Hongbo , Huang Wei 
Published: September 2023

Abstract
The molecular mechanism for nobiletin’s protective effect against heatstroke-induced acute lung injury (HS-ALI) remains largely unknown. Previous research has demonstrated that ferroptosis is an important pathogenic event in HS-ALI. Nobiletin is a natural polymethoxylated flavonoid. Herein, we investigated the potential contribution of nobiletin to HS-ALI by inhibiting ferroptosis. Heat stress was used to induce HS-ALI in mice, and MLE-12 cells were stimulated by heat stress in vitro. Nobiletin was administrated by gavage for 2 hours before HS induction. Biochemical kits, immunofluorescence staining, and western blotting were performed on the markers of ferroptosis. Our results showed that nobiletin administration significantly attenuated HS-induced lung injury and ferroptosis. Moreover, nobiletin pretreatment significantly reversed HS-induced p53 upregulation in vivo and in vitro. Pretreatment with a p53 agonist, Tenovin-6 partly abolished the protective effect of nobiletin in mice with HS-ALI. Meanwhile, p53 knockdown significantly increased GPX4 and SLC7A11 expression levels compared to the HS group in HS-induced MLE-12 cells. Subsequently, nobiletin ameliorated HS-induced MLE-12 cells ferroptosis by activating the SLC7A11/GPX4 pathway, while p53 overexpression effectively abolished the protective effect of nobiletin. Taken together, our findings reveal that nobiletin attenuates HS-ALI by inhibiting ferroptosis through the p53/SLC7A11 pathway, indicating it to be a potential therapeutic agent for HS-ALI prevention and treatment.
Long-term Catch-up Growth and Risk Factors for Short Adult Height After Pediatric Liver Transplantation: A Retrospective Study
Authors: Umemura Kentaro , Mita Atsuyoshi , Ohno Yasunari , Masuda Yuichi , Yoshizawa Kazuki , Kubota Koji , Notake Tsuyoshi , Hosoda Kiyotaka , Yasukawa Koya , Kamachi Atsushi , Goto Takamune , Tomida Hidenori , Yamazaki Shiori , Shimizu Akira , Soejima Yuji 
Published: September 2023

Background.
Children requiring liver transplantation generally have severe growth retardation. Recipients experience posttransplantation catch-up growth, although some show short adult heights. We aimed to determine decades-long catch-up growth trends and risk factors for short adult height following liver transplantation.

Methods.
We analyzed long-term height Z scores and risk factors for short adult height in a single-center retrospective cohort of 117 pediatric liver transplantation recipients who survived >5 y, with 75 of them reaching adult height.

Results.
Median age at transplantation was 1.3 y, and the most common primary diagnosis was biliary atresia (76.9%). Mean height Z scores pretransplantation and 1, 3, and 8 y after transplantation were –2.26, –1.59, –0.91, and –0.59, respectively. The data then plateaued until 20 y posttransplantation when mean adult height Z score became –0.88, with a median follow-up of 18.6 y. Nineteen recipients did not show any catch-up growth, and one quarter of recipients had short adult height (<5th percentile of the healthy population). Multivariate analysis identified old age (odds ratio, 1.22 by 1 y; P = 0.002), low height Z scores at transplantation (odds ratio, 0.46 by 1 point; P < 0.001), and posttransplantation hospital stay ≥60 d (odds ratio, 4.95; P = 0.015) as risk factors for short adult height. In contrast, prolonged steroid use after transplantation was not considered a significant risk factor.

Conclusions.
Although tremendous posttransplantation catch-up growth was observed, final adult height remained inadequate. For healthy physical growth, liver transplantation should be performed as early as possible, before growth retardation becomes severe.
Heat stress and the temporal dynamics of insect growth
Authors: Kingsolver Joel G. , Shlichta J. Gwen , Moore M. Elizabeth 
Published: September 2023

AbstractTemperature affects rates of ingestion, growth and other key processes in insects and other ectotherms, a relationship described by the thermal performance curve. But the history of temperature exposure can cause stress or acclimation responses, altering the relationship between current temperature and performance. The temporal dynamics of such time-dependent effects for ectotherm growth are poorly understood. We quantify how growth and ingestion change over time at different constant temperatures during the final larval instar for two thermal-generalist insect species,Pieris rapae L.andManduca sexta L. Initial growth rates were greatest at higher temperatures for bothP. rapae(29-35 °C) andM. sexta(34-38 °C); but growth rates at higher temperatures declined over time. As a result, the optimal and maximal temperatures for growth declined over time (2-4 days) in both species. UnlikeP. rapae,M. sextacould maintain growth and survival to wandering and pupation at temperatures above 35 °C. ForM. sextalarvae at 40 °C, ingestion continues even as growth declines, suggesting that post-ingestive processes limit growth rates at these high temperatures. Our results show how time-dependent effects at higher temperatures develop over hourly to daily time scales, with important consequences for understanding and modeling organismal responses to heat waves and extreme temperature events.
Menopause status and within group differences in chronological age affect the functional neural correlates of spatial context memory in middle-aged females
Authors: Crestol Arielle , Rajagopal Sricharana , Lissaman Rikki , LaPlume Annalise , Pasvanis Stamatoula , Olsen Rosanna K. , Einstein Gillian , Jacobs Emily , Natasha Rajah M. 
Published: September 2023

AbstractReductions in the ability to encode and retrieve past experiences in rich spatial contextual detail (episodic memory) are apparent by midlife – a time when most females experience spontaneous menopause. Yet, little is known about how menopause status affects episodic memory-related brain activity at encoding and retrieval in middle-aged pre- and post-menopausal females, and whether any observed group differences in brain activity and memory performance correlate with chronological age within group. We conducted an event-related task fMRI study of episodic memory for spatial context to address this knowledge gap. Multivariate behavioral partial least squares (PLS) was used to investigate how chronological age and retrieval accuracy correlated with brain activity in 31 premenopausal (age range: 39.55 – 53.30 yrs,Mage= 44.28 yrs,SDage= 3.12 yrs) and 41 postmenopausal females (age range: 46.70 to 65.14 yrs,Mage= 57.56 yrs,SDage= 3.93 yrs). We found that postmenopausal status, and advanced age within post-menopause, was associated with lower spatial context memory. The fMRI analysis showed that only in postmenopausal females, advanced age was correlated with decreased activity in occipitotemporal, parahippocampal, and inferior parietal during encoding and retrieval, and poorer spatial context memory performance. In contrast, only premenopausal females exhibited an overlap in encoding and retrieval activity in angular gyrus, midline cortical regions, and prefrontal cortex, which correlated with better spatial context retrieval accuracy. These results highlight how menopause status and chronological age, nested within menopause group, affect episodic memory and its neural correlates at midlife.Significance StatementThis is the first fMRI study to examine how pre- and post-menopause status affects the neural correlates of episodic memory encoding and retrieval, and how chronological age contributes to any observed group similarities and differences. We found that both menopause status (endocrine age) and chronological age affect spatial context memory and its neural correlates. Menopause status directly affected the direction of age- and performance-related correlations with brain activity in inferior parietal, parahippocampal and occipitotemporal cortices across encoding and retrieval. Moreover, we found that only premenopausal females exhibited cortical reinstatement of encoding-related activity in midline cortical, prefrontal, and angular gyrus, at retrieval. This suggests that spatial context memory abilities may rely on distinct brain systems at pre-compared to post-menopause.
GENETIC COUNSELING IN THE MIDDLE EAST
Authors: Shenbagam Shruti , Taylor Alan , Jain Ruchi , Fakhro Khalid A. , Alkuraya Fowzan S. , Abou Tayoun Ahmad N. 
Published: September 2023

ABSTRACTGenomic advancements have led to increased utilization of genetic testing in clinical care, yet barriers to accessing genetic counseling and genomics services remain, particularly in the Middle East where inherited diseases are highly prevalent due to consanguinity. Limited knowledge of healthcare professionals’ experiences in genetic counseling in the Middle East necessitates understanding their perspectives for better service improvement in the region.A survey of 32 healthcare professionals providing genetic counseling services in the Middle East explored provider experiences, patient attitudes and cultural/psychosocial factors related to genetic testing. Among the respondents, 21 providers (65.6%), caring for patients of multiple ethnicities, including Arabs, recognised that there are unique challenges to counseling between these patient groups. Thematic data analysis identified that higher levels of consanguinity and stoic nature of the people are unique cultural considerations for this region. Language barriers and limited resources were identified as genetic counseling challenges. Overall, patients in the region demonstrated good coping abilities with a genetic diagnosis. Eighteen responses (56%) highlighted an overall positive attitude, with increasing awareness and acceptance towards genetic testing in this region. This study highlights the need for further research and interventions to address the unique challenges and improve genetic counseling services in the Middle East.What is known about this topic?Genetic counseling is typically provided by geneticists and genetic counselors, but due to the limited numbers in the Middle East, this service is also provided by other physicians across various specialties. There is limited knowledge regarding the experiences of healthcare providers offering genetic counseling services in the Middle East and the specific challenges they face in this region.What this paper adds to the topic?Our study offers valuable insights into the perspectives of healthcare providers regarding patient attitudes, cultural considerations, and psychosocial factors in genetic testing, with the aim of improving genetic counseling services and enhancing patient outcomes. These findings, along with our recommended strategies shed light on the unique dynamics of genetic counseling in the Middle East.