bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of age-dependent features of human bronchi using explainable artificial intelligence
Authors: Ikushima Hiroaki , Usui Kazuhiro 
Published: August 2023

BackgroundAgeing induces functional and structural alterations in organs, and age-dependent parameters have been identified in various medical data sources. However, there is currently no specific clinical test to quantitatively evaluate age-related changes in bronchi. This study aimed to identify age-dependent bronchial features using explainable artificial intelligence for bronchoscopy images.MethodsThe present study included 11 374 bronchoscopy images, divided into training and test datasets based on the time axis. We constructed convolutional neural network (CNN) models and evaluated these models using the correlation coefficient between the chronological age and the “bronchial age” calculated from bronchoscopy images. We employed gradient-weighted class activation mapping (Grad-CAM) to identify age-dependent bronchial features that the model focuses on. We assessed the universality of our model by comparing the distribution of bronchial age for each respiratory disease or smoking history.ResultsWe constructed deep-learning models using four representative CNN architectures to calculate bronchial age. Although the bronchial age showed a significant correlation with chronological age in each CNN architecture, EfficientNetB3 achieved the highest Pearson's correlation coefficient (0.9617). The application of Grad-CAM to the EfficientNetB3-based model revealed that the model predominantly attended to bronchial bifurcation sites, regardless of whether the model accurately predicted chronological age or exhibited discrepancies. There were no significant differences in the discrepancy between the bronchial age and chronological age among different respiratory diseases or according to smoking history.ConclusionBronchial bifurcation sites are universally important age-dependent features in bronchi, regardless of the type of respiratory disease or smoking history.
Are the outcomes of single-stage open reduction and Dega osteotomy the same when treating DDH in patients younger than 8 years old? A prospective cohort study
Authors: Zein AboBakr , Khalifa Ahmed A. , Elsherif Mohamed Eslam , Elbarbary Hassan , Badaway Mohamed Youness 
Published: August 2023

Abstract
Background
The primary objective was to report our early results after a one-stage procedure [open reduction (OR), Dega pelvic osteotomy (DPO), and femoral osteotomy (FO) when needed] for surgical management of a cohort of patients with developmental dysplasia of the hip (DDH). The secondary objective was to compare the functional, radiological, and complications among patients younger and older than 30 months.

Materials and methods
This prospective cohort study included 71 hips with DDH in 61 patients with a mean age of 34.3 ± 19.5 months. All patients underwent one-stage surgical procedures, including OR + DPO and FO, if needed. Functional and radiographic assessment at the last follow-up was conducted using the modified Severin grading system and the Severin classification system, respectively, in addition to assessing the acetabular index (AI), osteotomies healing, and presence of complications. We divided patients into two groups, younger than 30 months (group I) and older than 30 months (group II).

Results
We included 35 hips in group I and 36 in group II. All hips received OR + DPO, while 25 (69.4%) hips in group II had FO. The operative time was significantly longer in group II (103.19 ± 20.74 versus 72.43 ± 11.59 min, p < 0.001). After a mean follow up of 21.3 ± 2.3 months, the functional outcomes were satisfactory in 62 (87.3%) hips (94.3% in group I and 80.6% in group II, p = 0.35). There was a significant improvement in the AI in all patients compared with preoperative values (27.2° ± 2.9 versus 37° ± 4.2, p < 0.05). Furthermore, 63 (88.7%) hips had satisfactory radiographic outcomes (94.3% in group I and 83.3% in group II, p = 0.26), and all osteotomies showed radiographic healing. The overall complications incidence was significantly lower in group I compared with group II (5.7% versus 30.6%, p < 0.05), and avascular necrosis occurred in 4 (5.6%) hips, all in group II (p = 0.06).

Conclusion
One-stage procedure entailing open reduction, Dega pelvic osteotomy, and femoral osteotomy when needed for managing DDH in patients younger than eight years old revealed acceptable clinical and radiological outcomes. However, there was a higher need for a concomitant femoral osteotomy in patients older than 2.5 years, and complications were more frequent.
Level of evidence III
Prenatal lipopolysaccharide exposure induces anxiety-like behaviour in male mouse offspring and aberrant glial differentiation of embryonic neural stem cells
Authors: Chen Chie-Pein , Chen Pei-Chun , Pan Yu-Ling , Hsu Yi-Chao 
Published: August 2023

Abstract
Background
Prenatal infection has been implicated in the development of neuropsychiatric disorders in children. We hypothesised that exposure to lipopolysaccharide during prenatal development could induce anxiety-like behaviour and sensorineural hearing loss in offspring, as well as disrupt neural differentiation during embryonic neural development.

Methods
We simulated prenatal infection in FVB mice and mouse embryonic stem cell (ESC) lines, specifically 46C and E14Tg2a, through lipopolysaccharide treatment. Gene expression profiling analyses and behavioural tests were utilized to study the effects of lipopolysaccharide on the offspring and alterations in toll-like receptor (TLR) 2-positive and TLR4-positive cells during neural differentiation in the ESCs.

Results
Exposure to lipopolysaccharide (25 µg/kg) on gestation day 9 resulted in anxiety-like behaviour specifically in male offspring, while no effects were detected in female offspring. We also found significant increases in the expression of GFAP and CNPase, as well as higher numbers of GFAP + astrocytes and O4+ oligodendrocytes in the prefrontal cortex of male offspring. Furthermore, increased scores for genes related to oligodendrocyte and lipid metabolism, particularly ApoE, were observed in the prefrontal cortex regions. Upon exposure to lipopolysaccharide during the ESC-to-neural stem cell (NSC) transition, Tuj1, Map2, Gfap, O4, and Oligo2 mRNA levels increased in the differentiated neural cells on day 14. In vitro experiments demonstrated that lipopolysaccharide exposure induced inflammatory responses, as evidenced by increased expression of IL1b and ApoB mRNA.

Conclusions
Our findings suggest that prenatal infection at different stages of neural differentiation may result in distinct disturbances in neural differentiation during ESC—NSC transitions. Furthermore, early prenatal challenges with lipopolysaccharide selectively induce anxiety-like behaviour in male offspring. This behaviour may be attributed to the abnormal differentiation of astrocytes and oligodendrocytes in the brain, potentially mediated by ApoB/E signalling pathways in response to inflammatory stimuli.
In-silico analysis of heat shock transcription factor (OsHSF) gene family in rice (Oryza sativa L.)
Authors: Shamshad Areeqa , Rashid Muhammad , Zaman Qamar uz 
Published: August 2023

Abstract
Background
One of the most important cash crops worldwide is rice (Oryza sativa L.). Under varying climatic conditions, however, its yield is negatively affected. In order to create rice varieties that are resilient to abiotic stress, it is essential to explore the factors that control rice growth, development, and are source of resistance. HSFs (heat shock transcription factors) control a variety of plant biological processes and responses to environmental stress. The in-silico analysis offers a platform for thorough genome-wide identification of OsHSF genes in the rice genome.

Results
In this study, 25 randomly dispersed HSF genes with significant DNA binding domains (DBD) were found in the rice genome. According to a gene structural analysis, all members of the OsHSF family share Gly-66, Phe-67, Lys-69, Trp-75, Glu-76, Phe-77, Ala-78, Phe-82, Ile-93, and Arg-96. Rice HSF family genes are widely distributed in the vegetative organs, first in the roots and then in the leaf and stem; in contrast, in reproductive tissues, the embryo and lemma exhibit the highest levels of gene expression. According to chromosomal localization, tandem duplication and repetition may have aided in the development of novel genes in the rice genome. OsHSFs have a significant role in the regulation of gene expression, regulation in primary metabolism and tolerance to environmental stress, according to gene networking analyses.

Conclusion
Six genes viz; Os01g39020, Os01g53220, Os03g25080, Os01g54550, Os02g13800 and Os10g28340 were annotated as promising genes. This study provides novel insights for functional studies on the OsHSFs in rice breeding programs. With the ultimate goal of enhancing crops, the data collected in this survey will be valuable for performing genomic research to pinpoint the specific function of the HSF gene during stress responses.
Circadian, Reward, and Emotion Systems in Teens prospective longitudinal study: protocol overview of an integrative reward-circadian rhythm model of first onset of bipolar spectrum disorder in adolescence
Authors: Alloy Lauren B. , Walsh Rachel F. L. , Smith Logan T. , Maddox Mackenzie A. , Olino Thomas M. , Zee Phyllis C. , Nusslock Robin 
Published: August 2023

Abstract
Background
Bipolar spectrum disorders (BSDs) are associated with a heightened sensitivity to rewards and elevated reward-related brain function in cortico-striatal circuitry. A separate literature documents social and circadian rhythm disruption in BSDs. Recently, integrated reward-circadian models of BSDs have been proposed. These models draw on work indicating that the two systems influence each other and interact to affect mood functioning. When dysregulated, reward and circadian system signaling may combine to form a positive feedback loop, whereby dysregulation in one system exacerbates dysregulation in the other. Project CREST (Circadian, Reward, and Emotion Systems in Teens) provides a first systematic test of reward-circadian dysregulation as a synergistic and dynamic vulnerability for first onset of BSD and increases in bipolar symptoms during adolescence.

Methods
This NIMH-funded R01 study is a 3-year prospective, longitudinal investigation of approximately 320 community adolescents from the broader Philadelphia area, United States of America. Eligible participants must be 13–16 years old, fluent in English, and without a prior BSD or hypomanic episode. They are being selected along the entire dimension of self-reported reward responsiveness, with oversampling at the high tail of the dimension in order to increase the likelihood of BSD onsets. At Times 1–6, every 6 months, participants will complete assessments of reward-relevant and social rhythm disruption life events and self-report and diagnostic assessments of bipolar symptoms and episodes. Yearly, at Times 1, 3, and 5, participants also will complete self-report measures of circadian chronotype (morningness-eveningness) and social rhythm regularity, a salivary dim light melatonin onset (DLMO) procedure to assess circadian phase, self-report, behavioral, and neural (fMRI) assessments of monetary and social reward responsiveness, and a 7-day ecological momentary assessment (EMA) period. During each EMA period, participants will complete continuous measures of sleep/wake and activity (actigraphy), a daily sleep diary, and three within-day (morning, afternoon, evening) measures of life events coded for reward-relevance and social rhythm disruption, monetary and social reward responsiveness, positive and negative affect, and hypo/manic and depressive symptoms. The fMRI scan will occur on the day before and the DLMO procedure will occur on the first evening of the 7-day EMA period.

Discussion
This study is an innovative integration of research on multi-organ systems involved in reward and circadian signaling in understanding first onset of BSD in adolescence. It has the potential to facilitate novel pharmacological, neural, and behavioral interventions to treat, and ideally prevent, bipolar conditions.
Comorbidities associated with the severity of COVID-19, and differences across ethnic groups: a UK Biobank cohort study
Authors: Patel Rahul , Kooner Jaspal S. , Zhang Weihua 
Published: August 2023

Abstract
Background
Disparities in COVID-19 outcomes exist on the basis of ethnicity and comorbidities. Minority ethnic groups in the UK are known to have poorer COVID-19 outcomes, but also an increased prevelance of certain comorbidities associated with severe outcomes. Additionally, despite the prevalence of certain psychiatric disorders there is a lack of research establishing their relationship with COVID-19 outcomes.

Methods
We used UK Biobank data, involving 472,182 participants, to test for an association between comorbidities and COVID-19 diagnosis (n = 30,901); and to test for an association between comorbidities and severe COVID-19 (n = 3182). This was done by performing univariable and multivariable logistic regression analysis, estimating odds ratios (ORs) and their 95% confidence intervals (95% CIs). The comorbidities studied were coronary heart disease (CHD), hypertension, type II diabetes mellitus (T2DM), obesity, chronic kidney disease (CKD), depression and anxiety. Multivariable models were adjusted for various socioeconomic, demographic and health-related confounders. We then performed sub-group analysis by common UK ethnic groups (White, South Asian, and Black).

Results
Increased prevalence of all studied comorbidities was seen in both outcomes, compared to the rest of the cohort. All studied comorbidities were associated with an increased risk of COVID-19 infection and severity across all models. For example, the adjusted ORs (95% CI) for depression were 1.112 (1.083 – 1.161) for COVID-19 diagnosis and 2.398 (2.163 – 2.658) for severe COVID-19. Sub-group analysis revealed stronger associations of COVID-19 diagnosis and severe COVID-19 for South-Asian participants for CHD (OR 1.585 [95% CI 1.194–2.105] for COVID-19 diagnosis and 3.021 [1.683–5.390] for severe COVID-19), hypertension (1.488 [1.231–1.799]; 3.399 [1.862–6.206]) and T2DM (1.671 [1.346–2.076]; 5.412 [3.130–9.357]) compared to White participants (1.264 [1.195–1.336] and 1.627 [1.441–1.837] for CHD; 1.131 [1.097–1.116] and 2.075 [1.885–2.284] for hypertension; 1.402 [1.331–1.476] and 2.890 [2.596–3.216] for T2DM). Similar results were seen for Black participants with CKD and hypertension.

Conclusion
Specific comorbidities are risk factors for poorer COVID-19 outcomes, supporting targeted interventions and policy aimed at individuals with these comorbidities. Although further research is required, there’s also a need for targeted policies for ethnic minorities assessing the unique reasons they are at greater risk of poor COVID-19 outcomes.
The effect of preoperative short-term octreotide treatment to surgery in thyrotropin-secreting pituitary adenomas: a retrospective cohort study
Authors: Zhao Runsheng , Fan Kaiyu , Wan Weiqing 
Published: August 2023

Abstract
Background
To prevent thyroid storm and ensure surgical safety, it is imperative to regulate excessive thyroid hormone levels in patients with thyrotropin-secreting pituitary adenomas (TSHoma) prior to surgery. Somatostatin analogues (SSAs), such as octreotide, have showed efficacy in shrinking tumors, which may facilitate surgical resection. This retrospective study aimed to investigate the effect of shortterm preoperative octreotide treatment on the surgical outcome of TSHoma.

Methods
A total of 65 TSHoma patients from January 2010 to July 2019 were included in the study. Of these,41 patients received short-term preoperative octreotide (Sandostatin, intermittent subcutaneous injection) treatment and all patients subsequently underwent surgery. The following data were recorded: clinical manifestations, laboratory examinations, sellar region MRI, postoperative pathological and electron microscopy data, intraoperative situation, and follow-up (> 3 months) regarding hormone levels and tumor recurrence.

Results
There was no significant difference in the consistency and blood supply of the tumor between patients who received short-term preoperative octreotide treatment and those who did not. Additionally, preoperative short-term octreotide treatment (median of 10 days with a range of 6–18 days) did not significantly improve the rates of gross total resection (GTR) or biochemical remission. Moreover, electron microscopy revealed subcellular level impairments and cell apoptotic in the octreotide treated TSHoma specimens.

Conclusion
Preoperative octreotide treatment for the purpose of reducing excessive thyroid hormones may not enhance surgical outcomes, and the duration of octreotide treatment needs to be extended to fully benefit from the tumor-shrinking effects of SSAs.
Closing the health gap in Central Australia: reduction in Indigenous Australian inpatient self-discharge rates following routine collaboration with Aboriginal Health Workers
Authors: Cheok Tim , Berman Morgan , Delaney-Bindahneem Richard , Jennings Matthew Phillip , Bray Linda , Jaarsma Ruurd , Poonnoose Pradeep Mathew , Williams Kanishka , Jayasekera Narlaka 
Published: August 2023

Abstract
Background
Indigenous Australians experience significant socioeconomic disadvantage and healthcare disparity compared to non-Indigenous Australians. A retrospective cohort study to describe the association between rates of self-discharge in Indigenous orthopaedic patients and the introduction of routine Aboriginal Liaison Officers (ALO) within the Orthopaedic multi-disciplinary team (MDT) was performed.

Methods
ALO were introduced within our routine Orthopaedic MDT on the 22nd of February 2021. Two patient cohorts were analysed, Group 1; patients admitted in the 9-months prior to inclusion of ALO, and Group 2; patients admitted within 9-months thereafter. The primary outcome of interest was the rate of self-discharge among Indigenous patients. Secondary outcomes of interest were the stage of treatment when patients self-discharged, recurrent self-discharge, risk factors for self-discharge and association between self-discharge and length of hospital stay.

Results
Introduction of ALO within routine Orthopaedic MDT was associated with a significant 37% reduced risk of self-discharge among Indigenous patients (p = 0·009), and significantly fewer self-discharges before their definitive surgical and medical treatment (p = 0·0024), or before completion of postoperative intravenous antibiotic treatment (p = 0·030). There was no significant change in the risk of recurrent self-discharge (p = 0·557). Risk factors for self-discharge were younger age; pensioners or unemployed; residents of Alice Springs Town-Camps or of communities within 51 to 100 km of Alice Springs; and those diagnosed with lacerations of the upper limb, but without tendon injury, wound and soft tissue infections or osteomyelitis. In Group 2, the odds of self-discharge decreased with increased length of hospital stay (p = 0·040).

Conclusions
Routine inclusion of ALO within the Orthopaedic MDT reduced the risk of self-discharge in Indigenous patients. Those who self-discharged did so only after critical aspects of their care were met.
Cancer-on-chip: a 3D model for the study of the tumor microenvironment
Authors: Cauli Elisa , Polidoro Michela Anna , Marzorati Simona , Bernardi Claudio , Rasponi Marco , Lleo Ana 
Published: August 2023

AbstractThe approval of anticancer therapeutic strategies is still slowed down by the lack of models able to faithfully reproduce in vivo cancer physiology. On one hand, the conventional in vitro models fail to recapitulate the organ and tissue structures, the fluid flows, and the mechanical stimuli characterizing the human body compartments. On the other hand, in vivo animal models cannot reproduce the typical human tumor microenvironment, essential to study cancer behavior and progression. This study reviews the cancer-on-chips as one of the most promising tools to model and investigate the tumor microenvironment and metastasis. We also described how cancer-on-chip devices have been developed and implemented to study the most common primary cancers and their metastatic sites. Pros and cons of this technology are then discussed highlighting the future challenges to close the gap between the pre-clinical and clinical studies and accelerate the approval of new anticancer therapies in humans.
Differential effect on mortality of the timing of initiation of renal replacement therapy according to the criteria used to diagnose acute kidney injury: an IDEAL-ICU substudy
Authors: Barbar Saber Davide , Bourredjem Abderrahmane , Trusson Rémi , Dargent Auguste , Binquet Christine , Quenot Jean-Pierre ,   IDEAL-ICU Study, Clere-Jehl Raphaël , Hernu Romain , Montini Florent , Bruyère Rémi , Lebert Christine , Bohé Julien , Badie Julio , Eraldi Jean-Pierre , Rigaud Jean-Philippe , Levy Bruno , Siami Shidasp , Louis Guillaume , Bouadma Lila , Constantin Jean-Michel , Mercier Emmanuelle , Klouche Kada , Du Cheyron Damien , Piton Gaël , Annane Djillali , Jaber Samir , van der Linden Therry , Blasco Gilles , Mira Jean-Paul , Schwebel Carole , Chimot Loïc , Guiot Philippe , Nay Mai-Anh , Meziani Ferhat , Helms Julie , Roger Claire , Louart Benjamin 
Published: August 2023

Abstract
Background
This substudy of the randomized IDEAL-ICU trial assessed whether the timing of renal replacement therapy (RRT) initiation has a differential effect on 90-day mortality, according to the criteria used to diagnose acute kidney injury (AKI), in patients with early-stage septic shock.

Methods
Three groups were considered according to the criterion defining AKI: creatinine elevation only (group 1), reduced urinary output only (group 2), creatinine elevation plus reduced urinary output (group 3). Primary outcome was 90-day all-cause death. Secondary endpoints were RRT-free days, RRT dependence and renal function at discharge. We assessed the interaction between RRT strategy (early vs. delayed) and group, and the association between RRT strategy and mortality in each group by logistic regression.

Results
Of 488 patients enrolled, 205 (42%) patients were in group 1, 174 (35%) in group 2, and 100 (20%) in group 3. The effect of RRT initiation strategy on 90-day mortality across groups showed significant heterogeneity (adjusted interaction p = 0.021). Mortality was 58% vs. 42% for early vs. late RRT initiation, respectively, in group 1 (p = 0.028); 57% vs. 67%, respectively, in group 2 (p = 0.18); and 58% vs. 55%, respectively, in group 3 (p = 0.79). There was no significant difference in secondary outcomes.

Conclusion
The timing of RRT initiation has a differential impact on outcome according to AKI diagnostic criteria. In patients with elevated creatinine only, early RRT initiation was associated with significantly increased mortality. In patients with reduced urine output only, late RRT initiation was associated with a nonsignificant, 10% absolute increase in mortality.