bluuebunny/crossref_metadata_2025_split huggingface dataset:
Data from Breast Cancer Subtype–Specific Organotropism Is Dictated by FOXF2-Regulated Metastatic Dormancy and Recovery
Authors: Jiang Wen-Jing , Zhou Tian-Hao , Huang Huan-Jing , Li Lin-Sen , Tan Hao , Zhang Rui , Wang Qing-Shan , Feng Yu-Mei 
Published: February 2025

<div>Abstract<p>Breast cancer subtypes display different metastatic organotropism. Identification of the mechanisms underlying subtype-specific organotropism could help uncover potential approaches to prevent and treat metastasis. In this study, we found that forkhead box F2 (FOXF2) promoted the seeding and proliferative recovery from dormancy of luminal breast cancer (LumBC) and basal-like breast cancer (BLBC) cells in the bone by activating the NF-κB and BMP signaling pathways. FOXF2 promoted LumBC cell seeding but not proliferative recovery in the lung by activating the BMP signaling pathway. Conversely, FOXF2 suppressed the seeding and proliferative recovery of BLBC cells in the lung by repressing the TGFβ signaling pathway. FOXF2 directly upregulated RelA/p65 transcription and expression in LumBC and BLBC cells by binding to the RELA proximal promoter region and RelA/p65 bound to the FOXF2 proximal promoter region to upregulate expression, forming a positive feedback loop. Targeting the NF-κB pathway efficiently prevented the metastasis of FOXF2-overexpressing breast cancer cells to the bone, whereas inhibiting TGFβ signaling blocked the metastasis of BLBC with low FOXF2 expression to the lung. These findings uncover critical mechanisms of breast cancer subtype–specific organotropism and provide insights into precision assessment and treatment strategies.</p><p><b>Significance:</b> FOXF2 regulates signaling pathways in a subtype-specific manner to coordinate the fate of disseminated breast cancer cells in distant organs, suggesting that FOXF2 functions could be harnessed to prevent organ-specific metastasis.</p><p><i><a href="https://aacrjournals.org/cancerres/article-abstract/doi/10.1158/0008-5472.CAN-24-4078" target="_blank">See related commentary by Bado, p. 639</a></i></p></div>
Thyroid-Stimulating Hormone Testing and Outcomes in Total Laryngectomy Patients
Authors: Warren James D. , Oglesby Kacie R. , Homan Carlton R. , Howe Edmund , Paul Oishika , Tassone Patrick , Kane Anne C. 
Published: February 2025

Objective: Assess timing and prevalence of thyroid-stimulating hormone (TSH) testing after total laryngectomy (TL). Identify prevalence of postoperative hypothyroidism and determine associations between thyroidectomy, postoperative hypothyroidism, and wound complications, including pharyngocutaneous fistula (PCF). Methods: Retrospective chart review performed at 2 tertiary care centers of adult patients undergoing TL between 2013 and 2021. Demographic data, perioperative labs and post-operative outcomes were collected. Analysis was performed. Results: Of 237 patients identified, thyroid removal was performed in 156 (65.8%), including 23 (9.7%) total thyroidectomies and 133 (56.1%) hemi-thyroidectomies. Of the 191 (80.6%) receiving postoperative TSH testing, 98 (41.4%) had TSH testing within 90 days, and 112 (58.6%) developed hypothyroidism. Mean postoperative TSH testing interval was 222.0 days (SSD 400.2), with variations associated with age ( P = .026), gender ( P = .009), PCF formation ( P < .001), history of radiation therapy (RT, P = .011), and preoperative levothyroxine use ( P = .031). Partial or total thyroid removal significantly increased the likelihood of high postoperative TSH (OR = 2.631, P = .002, 95% CI [1.410, 4.911]). PCF occurred in 62 (26.2%) patients, and there were no significant associations between pre/postoperative TSH or thyroid removal and PCF development or wound complications. Conclusion: Thyroidectomy was associated with elevated postoperative TSH levels, adding support to prior literature for consideration of avoiding thyroid removal during TL when appropriate. The wide range of TSH testing intervals and prevalence of postoperative hypothyroidism in our cohort highlights the importance of monitoring thyroid function in TL patients during the perioperative period.
Face-up vs face-down positioning after rhegmatogenous macula-off retinal detachment surgery: Hypothesis of better recovery
Authors: Savastano Alfonso , Calabresi Valerio , Crincoli Emanuele , Savastano Maria Cristina , De Vico Umberto Umberto , D’Onofrio Nicola Claudio , Rizzo Stanislao , Govetto Andrea 
Published: February 2025

Purpose To evaluate the differences between two distinct patient postoperative positions following rhegmatogenous macula-off retinal detachment surgery. Methods In this consecutive clinical study, 26 patients were placed in either the face-up or face-down postoperative position group. Postoperative follow-ups were conducted at 1, 3, and 6 months using type 1 M-CHARTS, best-corrected visual acuity (BCVA), intraocular pressure, and optical coherence tomography imaging to evaluate the functional and anatomical outcomes after surgery. Results The average vision recovery at 6 months was 0.35159 +/- 0.30945 logarithm of the minimum angle of resolution (logMAR) for the face-up group and 0.81521+/- 0.46662 logMAR for the face-down group. At 6 months, the average horizontal type 1 M-CHARTS for the face-up group was 0.1615 +/- 0.1710 and 0.2846 +/- 0.2828 for the face-down group; and the average vertical type 1 M-CHARTS was 0.1615 +/- 0.1557 for the face-up group and 0.2846 +/- 0.1725 for the face-down group. Conclusion The face-up position demonstrated significant improvement in both metamorphopsia and BCVA, suggesting that slow reattachment of photoreceptors on the retinal pigment epithelium layer can result in better quality of sight recovery. Further studies with larger sample sizes are warranted to confirm these results. The study adhered to the guidelines of the Declaration of Helsinki.
Comparing Immunotherapy Versus Chemotherapy Alone as Second-Line Therapy for Malignant Tumors of the Biliary Tract: A Retrospective Study
Authors: Jiang Chengzhi , Yang Liu , Kong Ling Yang , Fang Tianyuan , Chang Lele , He Lei , Ma Qian , Cheng YiBo , Wang Wanying , Ma Zhigang , Li Qingwei , Tao Ji 
Published: February 2025

Background: Bile duct carcinoma (BTC) is an uncommon malignant tumor of the gastrointestinal tract. Management is limited after the progress of first-line treatment. Immune checkpoint inhibitors (ICIs) have been proven popular in solid tumors. Immunotherapy plus chemotherapy has been a standard scheme in the management of multiple types of cancer. However, their efficacy and safety still need further exploration in patients who diagnosed BTC. This research mainly discusses the efficacy of immunotherapy in the second-line use of cholangiocarcinoma. Methods: In total, 126 individuals with BTC diagnosis from 2014 to 2024, who were treated with first-line or neoadjuvant treatment but were evaluated for progression or intolerance, were retrospectively included. All patients received standard chemotherapy, 57 received ICIs in combination with targeted therapy or not, and 69 did not. Patients were divided into simple chemotherapy (SC) and CT. Differences in efficacy, adverse events, progression-free survival (PFS), overall survival (OS), progressive disease (PD), and efficacy of multiple factors and efficacy were analyzed. The primary endpoint is defined as OS. The secondary endpoint is defined as PFS, objective response rate (ORR), disease control rate (DCR), and treatment-related adverse reactions (TRAEs). Results: The PFS and OS of 4.68 and 30.26 months for ICIs with or without targeted therapy were proven statistically significant ( P = .0012; P < .001). The ORR was 5.26% (3/57) in the CT group and 1.45% (1/69) in the SC group, and the DCR was 54.39% (31/57) compared with 33.33% (23/69). Cox analysis showed that TNM stage, T stage, histology grade, CA199 level, and treatment assessment grade were associated with OS ( P < .05). Histologic differentiation ( P = .009) and CA199 reduced ( P = .003) were proven as independent prognostic factors. The highest grade of 3 to 4 adverse reactions (TRAEs) was a reduction in hemoglobin (29.37%). Conclusion: Our work concluded that immunocombined chemotherapy with or without specific treatment showed significant antitumor activity and acceptable safety. Immune checkpoint inhibitors are likely to be a reliable second-line therapy for advanced BTC.
Frailty increases the risk of Alzheimer's disease in non-demented individuals: A longitudinal cohort study
Authors: Sheng Ze-Hu , Liu Jia-Yao , Ma Jun-Yi , Mi Yin-Chu , Wang Hao , Guo Fan , Ma Ling-Zhi , Tan Lan ,   Alzheimer's Disease Neuroimaging Initiative §
Published: February 2025

Background Frailty, which is considered a potential modifiable risk factor for dementia, continues to generate debate when it comes to Alzheimer's disease (AD). Furthermore, the underlying pathological mechanisms linking frailty to AD remain uncertain. Objective We aimed to investigate the relationship between frailty and the risk of AD while elucidating the connections between frailty, AD biomarkers, and cognitive function. Methods Total of 829 non-frail (261 robust, 568 pre-frail) and 94 frail individuals from the Alzheimer's Disease Neuroimaging Initiative database were recruited. Kaplan–Meier analysis and Cox regression assessed AD risk across diverse frail statuses in 923 non-demented individuals. Multiple linear regression, mixed effects models and causal mediation analyses bootstrapped 10,000 iterations were conducted to examined underlying associations. Results The frail group had a 67.7% increased risk of AD than non-frail group (HR = 1.677; 95%CI, 1.179–2.385; p = 0.004), a 61.8% increased risk of AD than pre-frail group (HR = 1.618; 95%CI, 1.131–2.316; p = 0.009) and a far higher risk of AD than robust group (HR = 2.011; 95%CI, 1.263–3.202; p = 0.003). Frailty was associated with cognitive decline (global cognition, memory and executive function), whole brain and hippocampus atrophy, and ventricle dilation. Higher frail degree predicted faster cognitive decline, brain atrophy and ventricle dilation. Frailty's association with cognition was partially mediated by volume of whole brain (29.54%–30.17% of total effect), hippocampus (18.21%–24.55% of total effect), and ventricle (baseline, 7.62%–10.87% of total effect; change rate, 13.30%–24.33% of total effect). Conclusions Frailty as a potential risk factor for AD, further mechanisms investigation is warranted; mitigating frailty could potentially contribute to AD prevention.
Association of hippocampal atrophy with tau pathology of temporal regions in preclinical Alzheimer's disease
Authors: Pan Ningning , Liu Shujuan , Ge Xinting , Zheng Yuanjie ,   for Alzheimer's Disease Neuroimaging Initiative
Published: February 2025

Background Hippocampal atrophy is linked to memory and cognitive deficits, preceding clinical diagnosis of mild cognitive impairment (MCI) by decades. Morphometry changes in the hippocampal formation (HF) and their relationship to tau deposition in non-demented individuals remains unclear. Objective To investigate morphometry changes in the HF and their association with tau deposition in a non-demented cohort. Methods Eighty-three subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) underwent T1-weighted MRI and Tau-PET scans at baseline and longitudinal follow-up. Participants were divided into amyloid-negative (Aβ−) and amyloid-positive (Aβ+) groups. Hippocampal volume/thickness were measured, and associations with tau deposition in temporal regions were examined using multivariable linear regression. Results No significant association was found between the hippocampal volume/thickness and tau deposition of temporal regions for the Aβ− group. For the Aβ+ group, the hippocampal thickness was significantly associated with tau deposition of entorhinal cortex (ERC) for both hemispheres, and temporal pole, inferior temporal, and middle temporal regions for right hippocampi with the longitudinal follow up scans, while no significant association with the baseline scans. It was interesting that there was strong association between the baseline tau deposition of ERC and temporal pole and the longitudinal follow up thickness of left hippocampi, while the associated regions for the right hemisphere were ERC, temporal pole, and inferior temporal regions. Conclusions Hippocampal atrophy may precede cognitive symptoms, with tau deposition in adjacent temporal regions contributing to hippocampal changes. The right HF appears more vulnerable than the left, indicating hemispheric differences in pathology.
Navigating financial coverage of healthcare to undocumented migrants at two hospitals in Oslo: a qualitative study
Authors: Fjelltorp-Veland Kristine , Fjeld Heidi E. , Eick Frode 
Published: February 2025

Aims: This study aimed to investigate how hospitals navigate financial coverage of healthcare for undocumented migrants, given the present laws and regulations in Norway. Methods: This qualitative study used an explorative approach. We collected and studied hospital guidelines for registering and invoicing foreign patients, and interviewed hospital staff from two university hospitals, and undocumented migrants at one non-governmental clinic in Oslo. The first author collected 14 documents and conducted 14 semi-structured, in-depth interviews. The project team used a thematic-analysis-inspired approach to identify patterns of shared meaning in the guidelines and interviews. Results: We found that the hospital guidelines did not account for undocumented migrants. The staff had to navigate between the guidelines and practical implications of undocumented migrant patients not having a resident permit and thus lacking a Norwegian identity number, bank card, or address. We found discrepancies between different staff’s expected roles in the registration of patients and in the assessment of patients’ ability to pay. The guidelines presumed an active patient and required documentation, which undocumented migrants had difficulty meeting. Conclusions: The underlying assumption of patients being documented in routines led to a process of othering of undocumented patients and thereby reproducing their marginalised position in the health system, hence depriving them of the right to ‘health care that is absolutely necessary and cannot wait’. We recommend that hospitals increase staff’s knowledge and capacity to ensure undocumented migrants’ right to healthcare.
Predictors for spontaneous pleurodesis in patients with indwelling pleural catheters for malignant pleural effusion: a safety net hospital experience
Authors: Farooq Saad , Armin Sabiha , Killingsworth Jordan E. , Agrawal Akriti , Rao Adishwar , Estrada-Y-Martin Rosa M. , Cherian Sujith V. 
Published: February 2025

Background: Malignant pleural effusion (MPE) affects approximately 150,000 patients in the United States each year and usually signifies advanced-stage cancer. The optimal treatment remains a challenge but indwelling pleural catheters (IPC) offer several advantages and may help achieve spontaneous pleurodesis (SP) in some patients. Objectives: We aim to investigate the predictors of SP among patients with MPE, particularly in a resource-limited community-based safety net hospital. Design: This is a retrospective cohort study done at a community-based safety net hospital. Methods: Adults diagnosed with or suspected of having MPE between January 2015 and December 2023 who underwent IPC placement were included. Data was collected retrospectively from December 2023 to June 2024. Data encompassed demographics, imaging, post-procedural complications, pleural fluid analysis, oncology treatment history, and utilization of medical thoracoscopy without chemical pleurodesis (MTWCP) for diagnosis. Results: A total of 173 patients underwent IPC insertion. Most of our patients were women (64.2%), and Latin American (65.9%), with a mean age of 55.3 years. The most common type of primary cancer was breast (28.9%) followed by lung (23.1%) and lymphoma (6.9%). Pleural fluid characteristics such as glucose, eosinophils, Lactate Dehydrogenase (LDH), and protein concentration were not significantly associated with SP. Most patients had low Eastern Cooperative Oncology Group scores of 0–2 (64.6%) and low LENT (Lactate Dehydrogenase (L), Eastern Cooperative Oncology Group (E) Performance Score, Neutrophil-to-Lymphocyte Ratio (N), and Tumor type (T) score) scores of 0–4 (59%). Lower scores (better functional status) were significantly associated with SP. Post-IPC chemotherapy and/or radiotherapy and immunotherapy were significantly associated with SP, adjusted odds ratio (OR) 7.295 (95% CI: 3.05–17.4, p = 0.001) and adjusted OR 6.261 (95% CI: 2.73–14.36, p = 0.001) respectively. MTWCP was also a predictor of SP with an adjusted OR of 4.031 (95% CI: 1.452–11.19, p = 0.007). Conclusion: Our study is the first to assess predictors of SP in a resource-limited safety net hospital representing under-represented and underserved patients. We identify several factors associated with higher rates of SP such as higher functional status, MTWCP, chemotherapy, immunotherapy, and radiation post-IPC placement. The study findings can help clinicians consider IPC placement and guide them regarding the duration and possible complications of IPC. MTWCP appears to improve the success of SP. Further studies are needed to assess these findings further.
Clinical outcomes in immunocompromised adults with COVID-19, based on anti-spike IgG serostatus and monoclonal antibody therapy: a retrospective cohort study in the Omicron period
Authors: Vasishta Shilpa , Aberg Judith , Patel Gopi , Gownivaripally Pooja Anand , Rana Meenakshi 
Published: February 2025

Background: Immunocompromised adults may experience severe COVID-19 outcomes, necessitating a multifaceted treatment approach. Studies from the Delta period showed benefit from monoclonal antibody (mAb) therapy that was most pronounced among anti-spike IgG seronegative individuals. With widespread vaccination and shifting SARS-CoV-2 variants in the Omicron period, clinical predictors of anti-spike IgG seronegativity, and impacts on clinical outcomes, remain incompletely characterized. Objectives: We describe outcomes from a cohort of immunocompromised adults with COVID-19 stratified by anti-spike IgG serostatus and receipt of mAb therapy during the Omicron period to evaluate clinical impact. Design: This was a retrospective study of immunocompromised adults with mild-moderate COVID-19 presenting between December 2021 and October 2022. Methods: Charts were reviewed to assess anti-spike IgG serostatus, receipt of mAb therapy, and 28-day outcomes including conventional oxygen use, high-flow oxygen use, mechanical ventilation, and death. Results: A total of 276 individuals were included, of whom 252 (91%) were partially or fully vaccinated, 190 (69%) were anti-spike IgG seropositive, and 225 (82%) received mAb therapy. A majority were solid organ transplant recipients (169, 61%), with anti-spike IgG seronegatively significantly associated with mycophenolate-based immunosuppression or comorbid chronic kidney disease. Conventional oxygen use among seropositive patients receiving mAb, seronegative patients receiving mAb, seropositive patients not receiving mAb, and seronegative patients not receiving mAb were 2/154 (1%), 5/71 (7%), 6/36 (17%), and 4/15 (27%), respectively. Across the cohort, high-flow oxygen use, mechanical ventilation, and death occurred in 6 (2%), 4 (3%), and 3 (1%) individuals, respectively. Conclusion: Clinical outcomes in a predominantly vaccinated, immunocompromised cohort with mild–moderate COVID-19 during the Omicron period appeared to vary with anti-spike IgG serostatus and receipt of mAb therapy. Observed trends would benefit from prospective studies during future iterations of COVID-19 therapeutics to inform treatment decisions for immunocompromised adults.
Barriers to and enhancement of the utilization of digital mental health interventions in low-resource settings: Perceptions of young people in Uganda
Authors: Mwaka Erisa Sabakaki , Bazzeketa Datsun , Mirembe Joy , Emoru Reagan D. , Twimukye Adelline , Kivumbi Apollo 
Published: February 2025

Introduction Digital mental health (DMH) enhances access to healthcare, particularly in low- and middle-income countries where investment in mental healthcare is low. However, utilization among young people (YP) is low. This study aimed to explore YP's perceptions of the barriers to the using of DMH interventions in low-resource settings. Methods A qualitative descriptive approach was used. Six face-to-face focus group discussions were conducted with 50 YP from nine universities in Uganda. The median age was 24 years (range 21–25 years) and respondents were drawn from diverse academic programmes with the majority being medical students (54%). A thematic approach was used to interpret the results. Results Three themes were identified from the data including perceptions of using DMH services, the perceived barriers to utilization, and suggestions for enhancement of DMH for YP in low-resource settings. Most respondents had a positive attitude towards DMH. The perceived barriers to utilization of DMH included the fear of stigma, affordability, inequitable access, privacy and confidentiality concerns, and app-related challenges. Access and use of DMH can be enhanced through public engagement, creating awareness, enhanced training, and access to affordable DMH interventions. Conclusion DMH was deemed important in extending healthcare to YP, particularly in health systems where traditional mental health services are not readily available. However, several factors hinder equitable access to DMH in low-resource settings. There is a need for long-term investment in digital health technologies.
Analysis of Clinical and Radiological Predictive Factors for Moderate and Severe Pulmonary Impairment in 102 Adolescent Idiopathic Scoliosis (AIS) Patients With Major Cobb Angle ≥45°: A Study of an Asian Population
Authors: Lee Sin Ying , Lee Yu Jie , Chiu Chee Kidd , Chandirasegaran Saturveithan , Hasan Mohd Shahnaz , Chan Chris Yin Wei , Kwan Mun Keong 
Published: February 2025

Study Design Retrospective cohort study. Objective To investigate the independent predictive factors for moderate-severe pulmonary impairment (MSPI) among adolescent idiopathic scoliosis (AIS) patients. Methods The preoperative pulmonary function tests (PFTs) of 102 AIS patients ( major Cobb angle ≥45°) operated between 2015 and 2020 were retrospectively reviewed. Patients were divided into 2 groups based on the predicted forced vital capacity (FVC) and forced expiratory volume in one second (FEV 1 ), respectively. Group 1 had normal/ mild pulmonary impairment ( FVC or FEV 1 >65% predicted) whereas Group 2 had MSPI ( FVC or FEV 1 ≤65% predicted). Multivariate logistic regression analysis was performed to determine the predictive factors for MSPI. Results 41.2% (N = 42) and 52.0% (N = 53) of the total patients were categorised into Group 2 (MSPI) based on predicted FVC and FEV1, respectively. In general, Group 2 had more patients with a major main thoracic (MT) curve, larger MT curve with lower MT flexibility, a larger MT apical vertebra translation (MT-AVT), and a smaller thoracolumbar-lumbar (TL/L) AVT than Group 1 ( P < . 05). When analyzing the MT Cobb angle for every 10 ° increment, patients with MT Cobb angle ≥70° had MSPI (N = 31.4%). Body mass index (BMI) (FVC: aOR .8; FEV1: aOR .9) and MT Cobb angle ( for every 10° increment, FVC: aOR 1.7; FEV1: aOR 1.8) were the significant independent predictive factors for MSPI. Conclusion MSPI was evident in patients with MT Cobb angle ≥70°, with MT Cobb angle and BMI being the significant independent predictive factors.