bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting ULK1 Decreases IFNγ-Mediated Resistance to Immune Checkpoint Inhibitors
Authors: Fenton Sarah E. , Zannikou Markella , Ilut Liliana , Fischietti Mariafausta , Ji Chunni , Oku Chidera V. , Horvath Curt M. , Le Poole I. Caroline , Bosenberg Marcus , Bartom Elizabeth T. , Kocherginsky Masha , Platanias Leonidas C. , Saleiro Diana 
Published: December 2022

AbstractImmune checkpoint inhibitors (ICI) have transformed the treatment of melanoma. However, the majority of patients have primary or acquired resistance to ICIs, limiting durable responses and patient survival. IFNγ signaling and the expression of IFNγ-stimulated genes correlate with either response or resistance to ICIs, in a context-dependent manner. While IFNγ-inducible immunostimulatory genes are required for response to ICIs, chronic IFNγ signaling induces the expression of immunosuppressive genes, promoting resistance to these therapies. Here, we show that high levels of Unc-51 like kinase 1 (ULK1) correlate with poor survival in patients with melanoma and overexpression of ULK1 in melanoma cells enhances IFNγ-induced expression of immunosuppressive genes, with minimal effects on the expression of immunostimulatory genes. In contrast, genetic or pharmacologic inhibition of ULK1 reduces expression of IFNγ-induced immunosuppressive genes. ULK1 binds IRF1 in the nuclear compartment of melanoma cells, controlling its binding to the programmed death-ligand 1 promoter region. In addition, pharmacologic inhibition of ULK1 in combination with anti-programmed cell death protein 1 therapy further reduces melanoma tumor growth in vivo. Our data suggest that targeting ULK1 represses IFNγ-dependent immunosuppression. These findings support the combination of ULK1 drug-targeted inhibition with ICIs for the treatment of patients with melanoma to improve response rates and patient outcomes.Implications:This study identifies ULK1, activated downstream of IFNγ signaling, as a druggable target to overcome resistance mechanisms to ICI therapy in metastatic melanoma.
Infiltration of Tumors Is Regulated by T cell–Intrinsic Nitric Oxide Synthesis
Authors: Cunha Pedro P. , Bargiela David , Minogue Eleanor , Krause Lena C.M. , Barbieri Laura , Brombach Carolin , Gojkovic Milos , Marklund Emilia , Pietsch Sandra , Foskolou Iosifina , Branco Cristina M. , Veliça Pedro , Johnson Randall S. 
Published: December 2022

AbstractNitric oxide (NO) is a signaling molecule produced by NO synthases (NOS1–3) to control processes such as neurotransmission, vascular permeability, and immune function. Although myeloid cell–derived NO has been shown to suppress T-cell responses, the role of NO synthesis in T cells themselves is not well understood. Here, we showed that significant amounts of NO were synthesized in human and murine CD8+ T cells following activation. Tumor growth was significantly accelerated in a T cell–specific, Nos2-null mouse model. Genetic deletion of Nos2 expression in murine T cells altered effector differentiation, reduced tumor infiltration, and inhibited recall responses and adoptive cell transfer function. These data show that endogenous NO production plays a critical role in T cell–mediated tumor immunity.
Unequal outcomes: The effects of the COVID-19 pandemic on mental health and wellbeing among Hispanic/Latinos with varying degrees of ‘Belonging’
Authors: Baxter Tatiana , Shenoy Sunil , Lee Hyeon-Seung , Griffith Taylor , Rivas-Baxter Angelica , Park Sohee 
Published: December 2022

Background: The COVID-19 pandemic has brought disparities in mental and physical health faced by ethnic minorities to the forefront. In the U.S., Hispanic/Latino communities are plagued by elevated rates of psychiatric conditions and trauma. Exacerbating this burden, common discourse often implicates Hispanic/Latino ethnicity as a causal factor, despite clear evidence of systemic causes, including lack of access to resources, and discrimination. Aims: To parse apart Hispanic/Latino ethnicity from determinants of wellbeing (such as trauma, financial status, and loneliness), we examined mental and physical health during COVID-19 via an online, anonymous survey available in both English and Spanish. Methods: We examined wellbeing across three participant groups, including two groups of Hispanic/Latino adults with varying degrees of ‘belonging’ to the dominant culture in their country of residence: Hispanic/Latino individuals living in Spanish-speaking and/or Central or Latin American countries (Group 1), Hispanic/Latino individuals living in the U.S. (Group 2), and non-Hispanic/Latino individuals living in the U.S. (Group 3). Results: Results demonstrated there were significant differences between groups in specific aspects of wellbeing. Most importantly, results showed Hispanic/Latino ethnicity does not significantly predict psychosocial wellbeing or psychosis risk, and identified several predictors of these outcomes, including U.S. residence, trauma, loneliness, and age. Conclusion: Our results demonstrate that Hispanic/Latino ethnicity itself is not a causal factor of poor psychosocial wellbeing or elevated psychosis risk and instead identify several social and systemic causal factors commonly faced by Hispanic/Latino Americans. We suggest that language reporting on minority mental health acknowledge systemic factors as contributing to poor outcome rather than referring to ethnicity as if it were a causal factor.
Culturally Acceptable Emotional Expressions Perceived by Non-U.S. Physicians Undergoing U.S.-Based Serious Illness Communication Skills Training: A Cross-Sectional Study
Authors: Onishi Eriko , Ishikawa Hirono , Ito Kaori , Nakagawa Shunichi , Shiozawa Youkie , Uemura Takeshi , Yuasa Misuzu , Ouchi Kei 
Published: December 2022

Context Responding to emotions is a key feature of U.S.-based serious illness communication skills training, VitalTalk®, of which trained actors portraying seriously ill patients is a component. The cultural appropriateness and perceived utility of the actors’ emotional expressions remain to be empirically evaluated outside of the U.S. Objectives To determine the cultural appropriateness and educational utility of VitalTalk® actors’ emotional expressions, as perceived by clinicians. Methods From January 2021-April 2022, we conducted a cross-sectional study of physicians in Japan attending virtual VitalTalk® training in Japanese, each session focusing on: responding to emotions (#1) and discussing goals of care (#2), respectively. We examined their perceived authenticity and utility of the actively and passively intense emotional expressions portrayed by actors in VitalTalk® role-plays. Results Physicians (N = 100, 94% response rate) from across Japan voluntarily attended two-session workshops and completed post-session surveys. Eighty-eight participants (88%) responded that both actively and passively intense emotions portrayed by the actors provided useful learning experiences. For session #1, the participants found actively intense emotional expressions to be more clinically authentic, compared to passively intense ones (4.21 vs 4.06 out of a 5-point Likert scale, P P= .02). For session #2, no such difference was observed (4.16 vs 4.08 of a 5-point Likert scale, P = .24). Conclusions Even in a culture where patients may express emotions passively, any intense and authentic emotional expressions by actors can be perceived as facilitating learning. Most participants perceived both the Name, Understand, Respect, Support, and Explore ‘(NURSE)' statements and Reframe, Expect emotion, Map out patient goals Align with goals and Propose a plan ‘(REMAP)' frameworks as useful in routine clinical practice in Japan.
Lumen diameter is associated with the patency after percutaneous angioplasty of arteriovenous fistulas
Authors: Li Dandan , Hao Ming , Sheng Haijun , Ge Hongwei , Zhu Yongbin 
Published: December 2022

Aim: To assess the value of lumen diameter after percutaneous angioplasty (PTA) to predict functional dialysis use (FDU) of arteriovenous fistulas (AVF). Methods: We performed a retrospective study of all patients who underwent first PTA because of AVF stenosis between March 2019 and March 2021. The outcome was FDU of AVF at 6 months follow up. Independent factors of FDU were identified using multivariate regression analyses. Receiver operating characteristic (ROC) curve was performed to investigate the predictive ability of lumen diameter for FDU. Results: A total 68 patients were included into this study and the AVF of 53 cases (77.9%) were good for FDU after 6 months. The AVF age was younger in failure group than that in success group (16.1 ± 9.1 months vs 28.3 ± 20.0 months, p = 0.026). Compared with failure group, the post-PTA minimum luminal diameter (MLD) was bigger in success group (4.5 [4.0–4.5 mm] vs 5.5 mm [4.5–5.5 mm], p < 0.001). Meanwhile, the gain of lumen diameter in success group was also bigger than that in failure group (2.5 mm [2.0–3.0 mm] in failure group vs 3.0 mm [2.75–3.5 mm] in success group, p = 0.012). The residual stenosis was higher in failure group than that in success group (30% [10%–40%] vs 10% [0%−20%], p = 0.003). Logistic regression showed that AVF age and post-PTA MLD were independent predictors of FDU. ROC analysis showed that the gain of lumen diameter, post-PTA MLD and improvement of stenosis were comparable to predict FDU. For post-PTA MLD, the area under ROC curve was 0.804 (95% CI, 0.681–0.927, p < 0.001). The best cutoff is 4.75 mm, with the sensitivity and specificity was 71.7% and 80.0%, respectively. Conclusions: AVF age and post-PTA MLD were independently predictors for FDU of AVF after PTA. To get the best performance, a minimum vein diameter of 4.75 mm should be obtained after angioplasty.
Association of daily physical activity with brain volumes and cervical spinal cord areas in multiple sclerosis
Authors: Block Valerie J , Cheng Shuiting , Juwono Jeremy , Cuneo Richard , Kirkish Gina , Alexander Amber M , Khan Mahir , Akula Amit , Caverzasi Eduardo , Papinutto Nico , Stern William A , Pletcher Mark J , Marcus Gregory M , Olgin Jeffrey E , Hauser Stephen L , Gelfand Jeffrey M , Bove Riley , Cree Bruce AC , Henry Roland G 
Published: December 2022

Background: Remote activity monitoring has the potential to evaluate real-world, motor function, and disability at home. The relationships of daily physical activity with spinal cord white matter and gray matter (GM) areas, multiple sclerosis (MS) disability and leg function, are unknown. Objective: Evaluate the association of structural central nervous system pathology with ambulatory disability. Methods: Fifty adults with progressive or relapsing MS with motor disability who could walk >2 minutes were assessed using clinician-evaluated, patient-reported outcomes, and quantitative brain and spinal cord magnetic resonance imaging (MRI) measures. Fitbit Flex2, worn on the non-dominant wrist, remotely assessed activity over 30 days. Univariate and multivariate analyses were performed to assess correlations between physical activity and other disability metrics. Results: Mean age was 53.3 years and median Expanded Disability Status Scale (EDSS) was 4.0. Average daily step counts (STEPS) were highly correlated with EDSS and walking measures. Greater STEPS were significantly correlated with greater C2-C3 spinal cord GM areas (ρ = 0.39, p = 0.04), total cord area (TCA; ρ = 0.35, p = 0.04), and cortical GM volume (ρ = 0.32, p = 0.04). Conclusion These results provide preliminary evidence that spinal cord GM area is a neuroanatomical substrate associated with STEPS. STEPS could serve as a proxy to alert clinicians and researchers to possible changes in structural nervous system pathology.
FLAIR hyperintense vessels on MRI post brain arteriovenous malformation embolization: A novel finding associated with post-procedure intraparenchymal hemorrhage
Authors: White Timothy G , A Shah Kevin , Fraser Madison , Turpin Justin , Teron Ina , W Link Thomas , Dehdashti Amir R , Woo Henry H 
Published: December 2022

Introduction Brain arteriovenous malformations (BAVMs) are frequently managed by endovascular embolization with a growing number of centers embolizing with intent to cure. Hemorrhage post-embolization is a severe and poorly understood complication. We present a novel imaging finding associated with post-embolization hemorrhage that has significantly impacted the management of patients at our institution. Methods A retrospective review of all patients undergoing embolization of BAVM at a single center was performed. Post-embolization magnetic resonance imaging (MRI) was reviewed for the presence of T2 fluid-attenuated inversion recovery (FLAIR) hyperintense vessels (FHVs). Bivariate analysis was performed to determine associations between patient characteristics and risk of hemorrhage. Results A total of 50 patients underwent 75 embolization procedures. Forty-six post-embolization MRIs were available for review. There were four hemorrhages and 100% of those presented with FHV. In contrast, only 11.9% of embolization procedures without post-procedural hemorrhage had FHVs on MRI. In total, 18.7% of embolizations led to some morbidity or mortality, with only 6.7% leading to permanent morbidity or mortality. In bivariate analysis, only the presence of FHVs was correlated with the risk of hemorrhage ( p < 0.05). Conclusions This is the first series to describe the finding of hyperintense blood vessels on FLAIR imaging after embolization of BAVMs and correlate it with hemorrhage post embolization. This finding can help guide practitioners and potentially identify patients at risk of delayed hemorrhage post embolization.
MRI hip morphology is abnormal in unilateral DDH and increased lateral limbus thickness is associated with residual DDH at minimum 10-year follow-up
Authors: Schmaranzer Florian , Justo Pedro , Kallini Jennifer R , Ferrer Marianna G , Miller Patricia E , Matheney Travis , Bixby Sarah D , Novais Eduardo N 
Published: December 2022

Purpose: The purpose of the study was to compare the post-reduction magnetic resonance imaging morphology for hips that developed residual acetabular dysplasia, hips without residual dysplasia, and uninvolved contralateral hips in patients with unilateral developmental dysplasia of the hip undergoing closed or open reduction and had a minimum 10-year follow-up. Methods: Retrospective study of patients with unilateral dysplasia of the hip who underwent open/closed hip reduction followed by post-reduction magnetic resonance imaging. Twenty-eight patients with a mean follow-up of 13 ± 3 years were included. In the treated hips, residual dysplasia was defined as subsequent surgery for residual acetabular dysplasia or for Severin grade > 2 at latest follow-up. On post-reduction, magnetic resonance imaging measurements were performed by two readers and compared between the hips with/without residual dysplasia and the contralateral uninvolved side. Magnetic resonance imaging measurements included acetabular version, coronal/ axial femoroacetabular distance, acetabular depth–width ratio, osseous/cartilaginous acetabular indices, and medial/lateral (limbus) cartilage thickness. Results: Fifteen (54%) and 13 (46%) hips were allocated to the “no residual dysplasia” group and to the “residual dysplasia” group, respectively. All eight magnetic resonance imaging parameters differed between hips with residual dysplasia and contralateral uninvolved hips (all p < 0.05). Six of eight parameters differed (all p < 0.05) between hips with and without residual dysplasia. Among these, increased limbus thickness had the largest effect (odds ratio = 12.5; p < 0.001) for increased likelihood of residual dysplasia. Conclusions: We identified acetabular morphology and reduction quality parameters that can be reliably measured on the post-reduction magnetic resonance imaging to facilitate the differentiation between hips that develop with/without residual acetabular dysplasia at 10 years postoperatively. Level of evidence: level III, prognostic case-control study.
Novel plasma protein biomarkers from critically ill sepsis patients
Authors: Van Nynatten Logan R. , Slessarev Marat , Martin Claudio M. , Leligdowicz Aleks , Miller Michael R. , Patel Maitray A. , Daley Mark , Patterson Eric K. , Cepinskas Gediminas , Fraser Douglas D. 
Published: December 2022

Abstract
Background
Despite the high morbidity and mortality associated with sepsis, the relationship between the plasma proteome and clinical outcome is poorly understood. In this study, we used targeted plasma proteomics to identify novel biomarkers of sepsis in critically ill patients.

Methods
Blood was obtained from 15 critically ill patients with suspected/confirmed sepsis (Sepsis-3.0 criteria) on intensive care unit (ICU) Day-1 and Day-3, as well as age- and sex-matched 15 healthy control subjects. A total of 1161 plasma proteins were measured with proximal extension assays. Promising sepsis biomarkers were narrowed with machine learning and then correlated with relevant clinical and laboratory variables.

Results
The median age for critically ill sepsis patients was 56 (IQR 51–61) years. The median MODS and SOFA values were 7 (IQR 5.0–8.0) and 7 (IQR 5.0–9.0) on ICU Day-1, and 4 (IQR 3.5–7.0) and 6 (IQR 3.5–7.0) on ICU Day-3, respectively. Targeted proteomics, together with feature selection, identified the leading proteins that distinguished sepsis patients from healthy control subjects with ≥ 90% classification accuracy; 25 proteins on ICU Day-1 and 26 proteins on ICU Day-3 (6 proteins overlapped both ICU days; PRTN3, UPAR, GDF8, NTRK3, WFDC2 and CXCL13). Only 7 of the leading proteins changed significantly between ICU Day-1 and Day-3 (IL10, CCL23, TGFα1, ST2, VSIG4, CNTN5, and ITGAV; P < 0.01). Significant correlations were observed between a variety of patient clinical/laboratory variables and the expression of 15 proteins on ICU Day-1 and 14 proteins on ICU Day-3 (P < 0.05).

Conclusions
Targeted proteomics with feature selection identified proteins altered in critically ill sepsis patients relative to healthy control subjects. Correlations between protein expression and clinical/laboratory variables were identified, each providing pathophysiological insight. Our exploratory data provide a rationale for further hypothesis-driven sepsis research.
Afghan women’s empowerment and antenatal care utilization: a population-based cross-sectional study
Authors: Yeo Sarah , Bell Melanie , Kim Yu Ri , Alaofè Halimatou 
Published: December 2022

Abstract
Background
Although antenatal care (ANC) offers a unique opportunity to diagnose and prevent complications by mitigating modifiable risk, 38.2% of women did not complete any ANC visits in Afghanistan in 2015. Women empowerment is associated with increased use of ANC; however, there is no evidence of the effect of women empowerment on ANC in the country. Addressing this gap, we aimed to evaluate the association between women’s empowerment and ANC utilization based on the conceptual framework of women’s empowerment.

Methods
We analyzed data from the 2015 Afghanistan Demographic and Health Survey for 11,056 women. The association between four domains of women’s empowerment, including capability, access to resources, security, and decision-making and power, and at least four ANC visits was analyzed using a multivariable logistic regression.

Results
After adjusting for covariates, access to information (AOR 1.38, 95%CI 1.24, 1.54) and decision-making (AOR 1.16, 95%CI 1.08, 1.24) were positively associated with four or more ANC visits. Compared to those without any education, women with primary education (AOR 1.67, 95%CI 1.02, 2.72), secondary education (AOR 2.43, 95%CI 1.25, 4.70), and higher education (AOR 3.03, 95%CI 1.30, 7.07) had higher odds of least four ANC visits. However, asset ownership was negatively associated with ANC visits (AOR 0.72, 95%CI 0.56, 0.92). Variables related to security and literacy were not associated with the minimum ANC visits.

Conclusions
The mixed results of the study highlight the complex natures of women’s empowerment, warranting a more nuanced understanding of women’s empowerment in the context and future research that capture multidimensionality of women’s empowerment. Also, efforts to empower women, particularly those with no education and had less decision-making power and access to health information, could be an effective strategy to enhance ANC use in Afghanistan.
Mental health status of medical students during postgraduate entrance examination
Authors: Chen Fajiang , Chen Juanmei , Chen Baoxin , Mofatteh Mohammad , Wen Caijuan , Wellington Jack , Gong Dongchao , Yang Hailing , Zeng Zhiyi , Miao Xiaoyu , Wu Shaoyong , Chen Yimin 
Published: December 2022

AbstractBackgroundThe postgraduate entrance examination can be a milestone for many medical students to advance their careers. An increasing number of students are competing for limited postgraduate offers available, and failure to enter postgraduate studies can have adverse mental health consequences. In this paper, we aim to investigate the mental health status of medical students during the postgraduate application entrance examination and to provide a targeted basis for mental health education and psychological counselling.MethodsUsing the Symptom Checklist-90 scale (SCL-90) questionnaire, the mental health status of 613 students who passed two rounds of the Postgraduate Entrance Examination in 2019 to enroll in Guangzhou Medical University in China was evaluated and followed up for retesting 6 months later. We used SPSS 20.0 statistical software for comparative analysis, including One-Sample T-Test, Independent-Samples T-Test, Paired Samples T-Test and Chi-square Test.ResultsOur data showed that 12.10% of students had mental health problems during the postgraduate entrance examination, and it decreased significantly to 4.40% at the 6-month follow-up after the examination period finished (P < 0.01). Somatization was the most significant symptom of the students both during and after the postgraduate entrance examination stages. All SCL-90 factors were scored significantly lower both in and after the postgraduate entrance examination stages than the 2008 national college student norm score (P < 0.01). Excluding psychiatric factors, all other SCL-90 factors in the postgraduate entrance examination stage scored higher than the graduate stage (P < 0.05), and the total score of SCL-90 in female medical students was higher compared to male students (P < 0.05).ConclusionThe postgraduate entrance examination event has a significant negative influence on students’ mental health. The mental health of college and graduate students as an important part of their higher education experience should be systematically studied, and psychological counselling or help should be provided to them throughout their studies, specifically during the examination period. Educating applicants about mental health should be implemented during the postgraduate entrance examination curriculum.