bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of inadequate responders to advanced therapy among commercially-insured adult patients with Crohn’s disease and ulcerative colitis in the United States
Authors: Gibble Theresa Hunter , Naegeli April N. , Grabner Michael , Isenberg Keith , Shan Mingyang , Teng Chia-Chen , Curtis Jeffrey R. 
Published: March 2023

AbstractBackgroundThe purpose of this analysis was to assess the frequency of inadequate response over 1 year from advanced therapy initiation among patients with Crohn’s disease (CD) or ulcerative colitis (UC) in the United States using a claims-based algorithm. Factors associated with inadequate response were also analyzed.MethodsThis study utilized claims data of adult patients from the HealthCore Integrated Research Database (HIRD®) from January 01, 2016 to August 31, 2019. Advanced therapies used in this study were tumor necrosis factor inhibitors (TNFi) and non-TNFi biologics. Inadequate response to an advanced therapy was identified using a claims-based algorithm. The inadequate response criteria included adherence, switching to/added a new treatment, addition of a new conventional synthetic immunomodulator or conventional disease-modifying drugs, increase in dose/frequency of advanced therapy initiation, and use of a new pain medication, or surgery. Factors influencing inadequate responders were assessed using multivariable logistic regression.ResultsA total of 2437 patients with CD and 1692 patients with UC were included in this analysis. In patients with CD (mean age: 41 years; female: 53%), 81% had initiated TNFi, and 62% had inadequate response. In patients with UC (mean age: 42 years; female: 48%), 78% had initiated a TNFi, and 63% had an inadequate response. In both patients with CD and UC, inadequate response was associated with low adherence (CD: 41%; UC: 42%). Inadequate responders were more likely to be prescribed a TNFi (for CD: odds ratio [OR] = 1.94;p < 0.001; for UC: OR = 2.76;p < 0.0001).ConclusionMore than 60% of patients with CD or UC had an inadequate response to their index advanced therapy within 1 year after initiation, mostly driven by low adherence. This modified claims-based algorithm for CD and UC appears useful to classify inadequate responders in health plan claims data.
Characterisation of tumor microenvironment and prevalence of CD274/PD-L1 genetic alterations difference in colorectal Cancer
Authors: Yang Lin , Liu Shousheng , He Wenzhuo , Xiong Zhenchong , Xia Liangping 
Published: March 2023

AbstractBackgroundLarge-scale genomic alterations, especially CD274/PD-L1 gene amplification, have great impact on anti-PD-1 efficacy on cancers such as Hodgkin’s lymphoma. However, the prevalence of PD-L1 genetic alterations in colorectal cancer (CRC) and its correlation with the tumor immune microenvironment and clinical implications remain unknown.Materials and MethodsPD-L1 genetic alterations were evaluated in 324 patients with newly diagnosed CRC including 160 mismatch repair-deficient (dMMR) patients and 164 mismatch repair-proficient (pMMR) patients using fluorescence in situ hybridization (FISH) method. The correlation between PD-L1 and the expression of the common immune markers was analyzed.ResultsTotally 33 (10.2%) patients were identified with aberrant PD-L1 genetic alternations including deletion (2.2%), polysomy (4.9%), and amplification (3.1%); They had more aggressive features such as advanced stage (P = 0.02), shorter overall survival (OS) (P < 0.001) than patients with disomy. The aberrations correlated with positive lymph node (PLN) (p = 0.001), PD-L1 expression by immunohistochemistry (IHC) in tumor cells (TCs) or tumor-infiltrated immunocytes (ICs) (both p < 0.001), and pMMR (p = 0.029). When dMMR and pMMR were analyzed independently, the correlations of aberrant PD-L1 genetic alterations with PD-1 expression (p = 0.016), CD4 + T cells (p = 0.032), CD8 T + cells (p = 0.032) and CD68 + cells (p = 0.04) were only found in dMMR cohort.ConclusionsThe prevalence of PD-L1 genetic alterations was relatively low in CRC, but the aberrations usually correlate with aggressive nature. The correlation between PD-L1 genetic alterations and tumor immune features was only observed in dMMR CRC.
The hsa_circ_0000276-ceRNA regulatory network and immune infiltration in cervical cancer
Authors: Zhang Honglei , Wang Xiuting , Li Yaqin , Bai Ying , Li Qi , Wang Shuling , Wei Yimiao , Li Jiarong , Wen Songquan , Zhao Weihong 
Published: March 2023

Abstract
Background
Our previous studies have confirmed that miR-154-5p can regulate pRb expression, and thus, play a tumor suppressor role in HPV16 E7-induced cervical cancer. However, its upstream molecules have not been elucidated in the progression of cervical cancer. This study aimed to explore the role of the miR-154-5p upstream molecule, hsa_circ_0000276 in cervical cancer development and its possible mechanisms of action.

Methods
We detected differences in whole transcriptome expression profiles of cervical squamous carcinoma and tissues adjacent to cervical cancer tissues from patients using microarray technology to predict circular RNAs (circRNAs) with binding sites to miR-154-5p. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of hsa_circ_0000276 (which had the strongest binding capacity to miR-154 and was selected as the target molecule) in cervical cancer tissues, followed by in vitro functional assays. Downstream microRNAs (miRNAs) and mRNAs of hsa_circ_0000276 were identified using transcriptome microarray data and databases, while the protein–protein interaction networks were obtained using STRING. A competing endogenous RNA (ceRNA) network centered on hsa_circ_0000276 was constructed using Cytoscape and GO and KEGG databases. Abnormal expression and prognosis of critical downstream molecules were analyzed using gene databases and molecular experiments. qRT-PCR and western blot analysis was performed to verify the expression of candidate genes.

Results
We identified 4,001 differentially expressed circRNAs between HPV16-positive cervical squamous carcinoma and benign cervical tissues and 760 circRNAs targeting miR-154-5p, including hsa_circ_0000276. hsa_circ_0000276 and miR-154-5p directly bound, and hsa_circ_0000276 was upregulated, in cervical precancerous lesions and cervical cancer tissues and cells. Silencing hsa_circ_0000276 inhibited G1/S transition and cell proliferation and promoted apoptosis in SiHa and CaSki cells. Bioinformatics analysis showed that the hsa_circ_0000276 ceRNA network included 17 miRNAs and seven mRNAs, and downstream molecules of hsa_circ_0000276 were upregulated in cervical cancer tissues. These downstream molecules were associated with a poor prognosis and affected cervical cancer-associated immune infiltration. Of these, expression of CD47, LDHA, PDIA3, and SLC16A1 was downregulated in sh_hsa_circ_0000276 cells.

Conclusions
Our findings show that hsa_circ_0000276 exerts cancer-promoting effects in cervical cancer and is an underlying biomarker for cervical squamous cell carcinoma.
Spatial characterization and quantification of CD40 expression across cancer types
Authors: Bates Katherine M. , Vathiotis Ioannis , MacNeil Tyler , Ahmed Fahad Shabbir , Aung Thazin Nwe , Katlinskaya Yuliya , Bhattacharya Sabyasachi , Psyrri Amanda , Yea Steven , Parkes Amanda , Sadraei Nooshin Hashemi , Roychoudhury Siddhartha , Rimm David L. , Gavrielatou Niki 
Published: March 2023

Abstract
Background
CD40, a TNF receptor family member, is expressed by a variety of immune cells and is involved in the activation of both adaptive and innate immune responses. Here, we used quantitative immunofluorescence (QIF) to evaluate CD40 expression on the tumor epithelium of solid tumors in large patient cohorts of lung, ovarian, and pancreatic cancers.

Methods
Tissue samples from nine different solid tumors (bladder, breast, colon, gastric, head and neck, non-small cell lung cancer (NSCLC), ovarian, pancreatic and renal cell carcinoma), constructed in tissue microarray format, were initially assessed for CD40 expression by QIF. CD40 expression was then evaluated on the large available patient cohorts for three of the tumor types demonstrating high CD40 positivity rate; NSCLC, ovarian and pancreatic cancer. The prognostic impact of CD40 expression on tumor cells was also investigated.

Results
CD40 expression on tumor cells was found to be common, with 80% of the NSCLC population, 40% of the ovarian cancer population, and 68% of the pancreatic adenocarcinoma population displaying some degree of CD40 expression on cancer cells. All of three of these cancer types displayed considerable intra-tumoral heterogeneity of CD40 expression, as well as partial correlation between expression of CD40 on tumor cells and on surrounding stromal cells. CD40 was not found to be prognostic for overall survival in NSCLC, ovarian cancer, or pancreatic adenocarcinoma.

Conclusions
The high percentage of tumor cells expressing CD40 in each of these solid tumors should be considered in the development of therapeutic agents designed to target CD40.
Association between sedentary behavior and depression in US adults with chronic kidney disease: NHANES 2007–2018
Authors: Liu Lin , Yan Yuqin , Qiu Jingxian , Chen Qiongmei , Zhang Yujing , Liu Yun , Zhong Xiaoshi , Liu Yan , Tan Rongshao 
Published: March 2023

Abstract
Background
Depression increases the risk of adverse clinical outcomes in patients with chronic kidney disease. Physical activity has been shown to improve depressive symptoms in this population, but the relationship of sedentary behavior with depression has not been studied. In this study, we examined the relationship between sedentary behavior and depression in patients with chronic kidney disease.

Methods
This cross-sectional study included 5,205 participants aged ≥ 18 years with chronic kidney disease participating in the 2007–2018 National Health and Nutrition Examination Survey. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9). Recreation activity, work activity, walking or cycling for transportation, and sedentary behavior were measured using the Global Physical Activity Questionnaire. A series of weighted logistic regression models were used to investigate the aforementioned relationship.

Results
The prevalence of depression among US adults with chronic kidney disease was 10.97% in our study. In addition, sedentary behavior was strongly associated with higher levels of depressive symptoms, as measured by the PHQ-9 (P < 0.001). In the fully adjusted model, we found that compared with participants who had shorter durations of sedentary behavior, participants who had the highest durations of sedentary behavior had 1.69 times (odd ratio 1.69, 95% confidence interval: 1.27, 2.24) greater risk of being clinically depressed. After adjusting for confounding factors, subgroup analyses showed that the association between sedentary behavior and depression still existed in all stratifications.

Conclusion
We found an association between longer duration of sedentary behavior and more severe depression in US adults with chronic kidney disease; however, prospective studies with larger sample sizes are still needed to confirm the effects of sedentary behavior on depression in the chronic kidney disease population.
Prevalence of potentially traumatic events and symptoms of depression, anxiety, hazardous alcohol use, and post-traumatic stress disorder among people with HIV initiating HIV care in Cameroon
Authors: Parcesepe Angela M. , Filiatreau Lindsey M. , Ebasone Peter Vanes , Dzudie Anastase , Pence Brian W. , Wainberg Milton , Yotebieng Marcel , Anastos Kathryn , Pefura-Yone Eric , Nsame Denis , Ajeh Rogers , Nash Denis 
Published: March 2023

Abstract
Background
This study explored the relationship between specific types of potentially traumatic events (PTEs) and symptoms of mental health disorders among people with HIV (PWH) in Cameroon.

Methods
We conducted a cross-sectional study with 426 PWH in Cameroon between 2019–2020. Multivariable log binominal regression was used to estimate the association between exposure (yes/no) to six distinct types of PTE and symptoms of depression (Patient Health Questionnaire-9 score > 9), PTSD (PTSD Checklist for DSM-5 score > 30), anxiety (Generalized Anxiety Disorder-7 scale score > 9), and hazardous alcohol use (Alcohol Use Disorders Identification Test score > 7 for men; > 6 for women).

Results
A majority of study participants (96%) reported exposure to at least one PTE, with a median of 4 PTEs (interquartile range: 2–5). The most commonly reported PTEs were seeing someone seriously injured or killed (45%), family members hitting or harming one another as a child (43%), physical assault or abuse from an intimate partner (42%) and witnessing physical assault or abuse (41%). In multivariable analyses, the prevalence of PTSD symptoms was significantly higher among those who reported experiencing PTEs during childhood, violent PTEs during adulthood, and the death of a child. The prevalence of anxiety symptoms was significantly higher among those who reported experiencing both PTEs during childhood and violent PTEs during adulthood. No significant positive associations were observed between specific PTEs explored and symptoms of depression or hazardous alcohol use after adjustment.

Conclusions
PTEs were common among this sample of PWH in Cameroon and associated with PTSD and anxiety symptoms. Research is needed to foster primary prevention of PTEs and to address the mental health sequelae of PTEs among PWH.
Adolescence internalizing problems as a mediator between autism diagnosis in childhood and quality of life in emerging adults with and without autism: a 10-year longitudinal study
Authors: Andersen Per Normann , Orm Stian , Fossum Ingrid Nesdal , Øie Merete Glenne , Skogli Erik Winther 
Published: March 2023

AbstractBackgroundIndividuals with autism tend to have a reduced quality of life across their lifespan. This reduced quality of life may be a result of autism traits, mental distress, and poor person/environment fit. In this longitudinal study, we looked at the role of adolescence internalizing and externalizing problems in mediating the relationship between having an autism diagnosis from childhood and perceived quality of life as emerging adults.MethodsA total of 66 participants in a group of emerging adults with autism (mean age 22.2 years), and without autism (mean age 20.9 years) were assessed in three assessment waves (T1 at 12 years, T2 at 14 years, and T3 at 22 years of age). Parents filled out the Child Behavior Checklist at T2 and participants filled out the Perceived Quality of Life Questionnaire at T3. Total and indirect effects were tested in serial mediation analysis.ResultsThe results showed that internalizing problems fully mediated the association between childhood autism diagnosis and the quality of life in emerging adulthood, while externalizing problems did not.ConclusionOur findings suggest that attention to adolescent internalizing problems is important to improve the later quality of life for emerging adults with autism.
Primary hyperparathyroidism in young patients is associated with metabolic disorders: a prospective comparative study
Authors: Bibik Ekaterina E. , Dobreva Ekaterina A. , Elfimova Alina R. , Miliutina Anastasiia P. , Eremkina Anna K. , Gorbacheva Anna M. , Krupinova Julia A. , Koksharova Ekaterina O. , Sklyanik Igor A. , Mayorov Alexander Y. , Mokrysheva Natalia G. 
Published: March 2023

Abstract
Background
Components of metabolic syndrome can be observed in patients with primary hyperparathyroidism (PHPT). The link between these disorders remains unclear due to the lack of relevant experimental models and the heterogeneity of examined groups. The effect of surgery on metabolic abnormalities is also controversial. We conducted a comprehensive assessment of metabolic parameters in young patients with PHPT.

Methods
One-center prospective comparative study was carried out. The participants underwent a complex biochemical and hormonal examination, a hyperinsulinemic euglycemic and hyperglycemic clamps, a bioelectrical impedance analysis of the body composition before and 13 months after parathyroidectomy compared to sex-, age- and body mass index matched healthy volunteers.

Results
45.8% of patients (n = 24) had excessive visceral fat. Insulin resistance was detected in 54.2% of cases. PHPT patients had higher serum triglycerides, lower M-value and higher C-peptide and insulin levels in both phases of insulin secretion compared to the control group (p < 0.05 for all parameters). There were tendencies to decreased fasting glucose (p = 0.031), uric acid (p = 0.044) and insulin levels of the second secretion phase (p = 0.039) after surgery, but no statistically significant changes of lipid profile and M-value as well as body composition were revealed. We obtained negative correlations between percent body fat and osteocalcin and magnesium levels in patients before surgery.

Conclusion
PHPT is associated with insulin resistance that is the main risk factor of serious metabolic disorders. Surgery may potentially improve carbohydrate and purine metabolism.
Prevalence of anemia and its associated factors among patients with type 2 diabetes mellitus in a referral diabetic clinic in the north of Iran
Authors: Hizomi Arani Reyhane , Fakhri Farima , Naeimi Tabiee Mohammad , Talebi Fatemeh , Talebi Zahra , Rashidi Negin , Zahedi Maryam 
Published: March 2023

AbstractBackgroundPurposeThis study intended to investigate the prevalence of anemia and its associated factors among patients with type 2 diabetes mellitus (T2DM) in Gorgan, Iran.MethodsThis cross-sectional study was conducted on 415 (109 men) patients with T2DM referred to the referral diabetes clinic of Sayad Shirazi Hospital in Gorgan in 2021. Demographic information, anthropometric indices, past medical history, and some laboratory data on cell counts, serum blood glucose, HbA1c, creatinine, lipid/iron profiles, and urinary albumin were collected. The univariable and multivariable logistic regression analysis was applied to compute odds ratios (ORs) and 95% confidence intervals (CI) for potential associated factors, using SPSS version 21. The multivariable Model was adjusted for obesity, Hb A1c, T2DM duration, using glucose-lowering drugs (GLDs), chronic kidney disease (CKD), albuminuria, hypertriglyceridemia, and hypercholesterolemia. ResultsThe prevalence of anemia was 21.5% [95%CI: 17.6-25.7] among our total participants. The corresponding values for men and women were 20.2 (13.1-29.0) and 21.9 (17.4-27.0), respectively.The adjusted model revealed that obesity (OR, 1.94 [95% CI, 1.17–3.23]), T2DM duration for more than five years (OR, 3.12 [1.78–5.47]), albuminuria (OR, 6.37 [3.13–10.91]), chronic kidney disease (OR, 4.30 [ 2.83–7.29]) and hypertriglyceridemia (OR, 1.72 [ 1.21–2.77]) were significantly associated with prevalent anemia among patients with T2DM. Moreover, using insulin separately or in combination with oral GLDs associated positively with the prevalence of anemia with ORs of 2.60 [1.42-6.42] and 1.87 [1.30-4.37] , respectively.ConclusionAnemia had a high prevalence among patients with T2DM in the north of Iran (about 22%), which is associated with obesity, hypertriglyceridemia, duration of T2DM, and diabetic kidney disease.
Living through uncertainty: a qualitative study on leadership and resilience in primary healthcare during COVID-19
Authors: Karreinen Soila , Paananen Henna , Kihlström Laura , Janhonen Kristiina , Huhtakangas Moona , Viita-aho Marjaana , Tynkkynen Liina-Kaisa 
Published: March 2023

Abstract
Background
Resilience is often referred to when assessing the ability of health systems to maintain their functions during unexpected events. Primary healthcare forms the basis for the health system and thus its resilient responses are vital for the outcomes of the whole system. Understanding how primary healthcare organisations are able to build resilience before, during, and after unexpected or sudden shocks, is key to public health preparedness. This study aims to identify how leaders responsible for local health systems interpreted changes in their operational environment during the first year of COVID-19, and to elucidate how these views reflect aspects of resilience in healthcare.

Methods
The data consist of 14 semi-structured individual interviews with leaders of local health systems in Finland representing primary healthcare. The participants were recruited from four regions. An abductive thematic analysis was used to identify entities from the viewpoints of the purpose, resources, and processes of resilience in the healthcare organisation.

Results
Results were summarised as six themes, which suggest that embracing uncertainty is viewed by the interviewees a basis for primary healthcare functioning. Leading towards adaptability was regarded a distinct leadership task enabling the organisation to modify its functions according to demands of the changing operational environment. Workforce, knowledge and sensemaking, as well as collaboration represented what the leaders viewed as the means for achieving adaptability. The ability to adapt functioned to comprehensively meet the population’s service needs built on a holistic approach.

Conclusions
The results showed how the leaders who participated in this study adapted their work during changes brought on by the pandemic, and what they viewed as critical for maintaining organisational resilience. The leaders considered embracing uncertainty as a principal feature of their work rather than viewing uncertainty as aberrant and something to avoid. These notions, along with what the leaders considered as critical means for building resilience and adaptability should be addressed and elaborated in future research. Research on resilience and leadership should be conducted more in the complex context of primary healthcare, where cumulative stresses are encountered and processed continuously.