bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of discoidin domain receptor (DDR)-1 with nilotinib alters CSF miRNAs and is associated with reduced inflammation and vascular fibrosis in Alzheimer’s disease
Authors: Stevenson Max , Varghese Rency , Hebron Michaeline L. , Liu Xiaoguang , Ratliff Nick , Smith Amelia , Turner R. Scott , Moussa Charbel 
Published: May 2023

AbstractDiscoidin Domain Receptor (DDR)-1 is activated by collagen. Nilotinib is a tyrosine kinase inhibitor that is FDA-approved for leukemia and potently inhibits DDR-1. Individuals diagnosed with mild–moderate Alzheimer’s disease (AD) treated with nilotinib (versus placebo) for 12 months showed reduction of amyloid plaque and cerebrospinal fluid (CSF) amyloid, and attenuation of hippocampal volume loss. However, the mechanisms are unclear. Here, we explored unbiased next generation whole genome miRNA sequencing from AD patients CSF and miRNAs were matched with their corresponding mRNAs using gene ontology. Changes in CSF miRNAs were confirmed via measurement of CSF DDR1 activity and plasma levels of AD biomarkers. Approximately 1050 miRNAs are detected in the CSF but only 17 miRNAs are specifically altered between baseline and 12-month treatment with nilotinib versus placebo. Treatment with nilotinib significantly reduces collagen and DDR1 gene expression (upregulated in AD brain), in association with inhibition of CSF DDR1. Pro-inflammatory cytokines, including interleukins and chemokines are reduced along with caspase-3 gene expression. Specific genes that indicate vascular fibrosis, e.g., collagen, Transforming Growth Factors (TGFs) and Tissue Inhibitors of Metalloproteases (TIMPs) are altered by DDR1 inhibition with nilotinib. Specific changes in vesicular transport, including the neurotransmitters dopamine and acetylcholine, and autophagy genes, including ATGs, indicate facilitation of autophagic flux and cellular trafficking. Inhibition of DDR1 with nilotinib may be a safe and effective adjunct treatment strategy involving an oral drug that enters the CNS and adequately engages its target. DDR1 inhibition with nilotinib exhibits multi-modal effects not only on amyloid and tau clearance but also on anti-inflammatory markers that may reduce cerebrovascular fibrosis.
Smoking identified as preferred mode of opioid safe supply use; investigating correlates of smoking preference through a 2021 cross-sectional study in British Columbia
Authors: Kamal Ariba , Ferguson Max , Xavier Jessica C , Liu Lisa , Graham Brittany , Lock Kurt , Buxton Jane A. 
Published: May 2023

Abstract
Background
The increasing number of illicit drug toxicity deaths in British Columbia (BC) has led to calls for a regulated (pharmaceutical grade) supply of substances (“safe supply”). In order to inform safe supply recommendations, we aimed to identify why people currently smoke opioids and assess the preferred mode of consumption if people who use opioids were provided with opioid safe supply.

Methods
The BC Harm Reduction Client Survey (HRCS) is an annual survey that gathers information about people who use drugs' (PWUD) substance use characteristic with the goal of contributing to evidence-based policy. This study utilized data from the 2021 HRCS. The outcome variable was “prefer smoking opioid safe supply” (‘yes/no’). Explanatory variables included participants’ demographics, drug use, and overdose characteristics. Bivariate and hierarchical multivariable logistic regressions were conducted to identify factors associated with the outcome.

Results
Of 282 total participants who indicated a preference for a mode of consumption for opioid safe supply, 62.4% preferred a smokable option and 19.9% preferred to inject if provided with opioid safe supply. Variables significantly associated with the outcome (preferred smoking) included: being 19-29 years old (AOR=5.95, CI =1.93 – 18.31) compared to >50 years old, having witnessed an overdose in the last 6 months (AOR=2.26, CI=1.20 – 4.28), having smoked opioids in the last 3 days (AOR=6.35, CI=2.98 – 13.53) and having a preference to smoke stimulants safe supply (AOR=5.04, CI=2.53 – 10.07).

Conclusion
We found that over half of participants prefer smokable options when accessing opioid safe supply. Currently in BC, there are limited smokable opioid safe supply options as alternatives to the toxic street supply. To reduce overdose deaths, safe supply options should be expanded to accommodate PWUD that prefer smoking opioids.
The role of substance use treatment in reducing stigma after release from incarceration: A qualitative analysis
Authors: Moore Kelly E. , Wyatt Janan P. , Phillips Sarah , Burke Catherine , Bellamy Chyrell , McKee Sherry A. 
Published: May 2023

Abstract
Background
People with substance use disorders (SUD) who have been involved in the legal system often experience stigma upon reentry into the community after incarceration. Although substance use treatment can sometimes be a source of stigma, it may also reduce stigma by facilitating connections with providers, reducing distress, or helping people feel more integrated in their community. However, research has rarely examined the potential for treatment to reduce stigma.

Methods
This study examined stigma experiences and the degree to which substance use treatment reduced stigma among 24 people with SUDs who were receiving care in an outpatient treatment facility after release from incarceration. Qualitative interviews were conducted and analyzed using a content analysis approach.

Results
Participants reported negative self-judgements as well as perceiving negative judgments from the community upon reentry. With regard to stigma reduction, themes emerged around substance use treatment repairing strained family relationships and reducing participants’ self-stigma. Aspects of treatment that reportedly reduced stigma included the treatment facility having a nonjudgmental atmosphere, patients trusting the staff, and working with peer navigators who had lived experience of SUD and incarceration.

Conclusions
Results from this study suggest that substance use treatment has the potential to decrease the negative impacts of stigma upon release from incarceration, which continues to be a major barrier. Though more research on stigma reduction is needed, we suggest some preliminary considerations for treatment programs and providers.
Quantitative strong motion simulations at three locations in downtown Mashiki during the 2016 Kumamoto Earthquake (Mw 7.0) based on the nonlinear ground response analyses with soil liquefaction
Authors: Fukutake Kiyoshi , Yoshida Kazuhiro , Kawase Hiroshi , Nagashima Fumiaki , Sun Jikai 
Published: May 2023

AbstractThe mainshock of the 2016 Kumamoto Earthquake (Mw 7.0) caused extensive damage to buildings in downtown Mashiki, Kumamoto Prefecture, Japan. The heavy building damage in the area was associated with both strong ground motion and building response characteristics. Fortunately, there were two strong motion stations in the area and the observed records during the mainshock were distributed, showing peak ground velocities exceeding 100 cm/s on the surface. The level of shaking would be sufficient to make soft surface sediments nonlinear. To reproduce observed ground motions quantitatively, one-dimensional nonlinear effective-stress time-history analyses were conducted at three locations in downtown Mashiki. The input wave was employed as either the observed underground wave or simulated outcrop input motion based on the diffuse field theory. The main purpose of the study was twofold: to investigate the proper soil constitutive relationship and its nonlinear parameters based on the limited amount of in situ information, and to validate the method of input motion evaluation at the seismological bedrock level based on diffuse field theory. The nonlinear time history analyses using the on-site boring survey and the outcrop wave based on diffuse field theory showed that the waveform of the mainshock observed on the ground surface was explained with sufficient accuracy. In addition, the results of the effective stress analysis indicated that soil liquefaction might have occurred in the area with thick surface layers along the Akitsu River where the water table was considered to be quite shallow.
Graphical Abstract
Building low-cost simulators for invasive ultrasound-guided procedures using the V-model
Authors: Johnsson Vilma , Tolsgaard Martin Grønnebæk , Petersen Olav Bennike Bjørn , Svendsen Morten Bo Søndergaard 
Published: May 2023

AbstractThe use of medical simulators for training technical and diagnostic skills has rapidly increased over the past decade. Yet, most available medical simulators have not been developed based on a structured evaluation of their intended uses but rather out of expected commercial value. Moreover, educators often struggle to access simulators because of cost or because no simulators have been developed for a particular procedure. In this report, we introduce “the V-model” as a conceptual framework to illustrate how simulator development can be guided by the intended uses in an iterative fashion. Applying a needs-based conceptual framework when developing simulators is important to increase the accessibility and sustainability of simulation-based medical education. It will minimize the developmental barriers and costs, while at the same time improving educational outcomes. Two new simulators for invasive ultrasound-guided procedures are used as examples, the chorionic villus sampling model and the ultrasound-guided aspiration trainer. Our conceptual framework and the use cases can serve as a template for future simulator development and documentation hereof.
Crosstalk between the JAK2 and TGF-β1 signaling pathways in scleroderma-related interstitial lung disease targeted by baricitinib
Authors: Wang Dandan , Wei Yimei , Xu Lulu , Zhang Jie 
Published: May 2023

Abstract
Background and objective
Systemic sclerosis (SSc) is an immune-mediated rheumatic disease characterized by fibrosis and vascular lesions. Interstitial lung disease is an early complication of SSc and the main cause of death from SSc. Although baricitinib shows good efficacy in a variety of connective tissue diseases, its role in systemic sclerosis-related interstitial lung disease (SSc-ILD) is unclear. The objective of our study was to explore the effect and mechanism of baricitinib in SSc-ILD.

Methods
We explored crosstalk between the JAK2 and TGF-β1 pathways. In vivo experiments, SSc-ILD mice model were constructed by subcutaneous injection of PBS or bleomycin (7.5 mg/kg) and intragastric administration of 0.5% CMC-Na or baricitinib (5 mg/kg) once every two days. We used ELISA, qRT‒PCR, western blot and immunofluorescence staining to evaluate the degree of fibrosis. In vitro experiments, we used TGF-β1 and baricitinib to stimulate human fetal lung fibroblasts (HFLs) and assessed protein expression by western blot.

Results
The vivo experiments showed that baricitinib notably alleviated skin and lung fibrosis, decreased the concentration of pro-inflammatory factors and increased those of the anti-inflammatory factors. Baricitinib affected the expression of TGF-β1 and TβRI/II inhibitiing JAK2. In the vitro experiments, following the culture of HFLs with baricitinib or a STAT3 inhibitor for 48 h, the expression levels of TβRI/II decreased. Conversely, with successful inhibition of TGF-β receptors in HFLs, JAK2 protein expression decreased.

Conclusions
Baricitinib attenuated bleomycin-induced skin and lung fibrosis in SSc-ILD mice model by targeting JAK2 and regulating of the crosstalk between the JAK2 and TGF-β1 signaling pathways.
Reutilization of solid wastes to improve the hydromechanical and mechanical behaviors of soils — a state-of-the-art review
Authors: Liu Chih-Hsuan , Hung Ching 
Published: May 2023

AbstractThe rapid urbanization, industrialization, and population growth have led to a considerable rise in solid waste production, highlighting the need for efficient solid waste management and recycling methods. To address the challenge of solid waste production, an alternative solution is to repurpose it in geotechnical engineering. This offers promising benefits as solid waste exhibits various mechanisms that can improve soil's hydromechanical and mechanical behaviors. This review aims to comprehensively analyze the effects and potential application of various solid waste types to stabilize and reinforce soil. The impacts and research trends of industrial waste, such as fly ash, red mud, ground granulated blast-furnace slag, and construction and demolition waste, as well as agricultural and municipal solid wastes, including rice husk ash, press mud, used waste tires, and face masks, on soil properties were identified. The findings contribute to a better understanding of the potential of solid waste as a sustainable and cost-effective solution for improving soil quality, highlighting new research themes in this area. A wide range of innovative methods to stabilize and reinforce soil have also been proposed; however, ingenious and effective containment techniques, as well as addressing the potential impacts of climate change on stabilized and reinforced soils (SRS), still need to be developed for robust field applications. This state-of-the-art review offers useful insights into the reutilization of solid wastes as a promising alternative for improving the hydromechanical and mechanical behaviors of SRS.
Identifying Patterns and Barriers in OncotypeDX Recurrence Score Testing in Older Patients With Early-Stage, Estrogen Receptor–Positive Breast Cancer: Implications for Guidance and Reimbursement
Authors: Trapani Dario , Jin Qingchun , Block Caroline C. , Freedman Rachel A. , Lin Nancy U. , Tarantino Paolo , Mittendorf Elizabeth A. , King Tari A. , Lester Susan C. , Brock Jane E. , Tayob Nabihah , Bunnell Craig A. , Tolaney Sara M. , Burstein Harold J. 
Published: May 2023

PURPOSE To evaluate the clinical patterns of utilization of OncotypeDX Recurrence Score (RS) in early-stage, hormone receptor–positive, human epidermal growth factor receptor 2–negative breast cancer (BC) at an academic center with previously established internal reflex testing guidelines. METHODS RS testing in accordance with preexisting reflex criteria and predictors of utilization outside of reflex criteria were retrospectively analyzed for the years 2019-2021 in a quality improvement evaluation. Patients were grouped according to OncotypeDX testing within (cohort A) or outside (cohort B) of predefined criteria which included a cap at age older than 65 years. RESULTS Of 1,687 patients whose tumors had RS testing, 1,087 were in cohort A and 600 in cohort B. In cohort B, nearly half of patients were older than 65 years (n = 279; IQR, 67-72 years). For patients older than 65 years, those with RS testing were younger (median age: 69 v 73 years), with higher grade cancers (G2-3: 84.9% v 54.7%) and were more likely to be treated with chemotherapy (15.4% v 4.1%). Issues for implementation of RS testing in older patients were identified, including potential structural barriers related to the current policy on the reimbursements of genomic tests. CONCLUSION Internal guidelines may facilitate standardized utilization of the RS in early-BC. Our data suggest that clinicians preferred broader utilization of RS across the age spectrum, with therapeutically important consequences. Modifying the current policy for reimbursement of RS testing and in internal reflexive testing criteria for those older than 65 years is warranted.
Endocrine Health and Health Care Disparities in the Pediatric and Sexual and Gender Minority Populations: An Endocrine Society Scientific Statement
Authors: Diaz-Thomas Alicia M , Golden Sherita Hill , Dabelea Dana M , Grimberg Adda , Magge Sheela N , Safer Joshua D , Shumer Daniel E , Stanford Fatima Cody 
Published: May 2023

Abstract
Endocrine care of pediatric and adult patients continues to be plagued by health and health care disparities that are perpetuated by the basic structures of our health systems and research modalities, as well as policies that impact access to care and social determinants of health. This scientific statement expands the Society's 2012 statement by focusing on endocrine disease disparities in the pediatric population and sexual and gender minority populations. These include pediatric and adult lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA) persons. The writing group focused on highly prevalent conditions—growth disorders, puberty, metabolic bone disease, type 1 (T1D) and type 2 (T2D) diabetes mellitus, prediabetes, and obesity. Several important findings emerged. Compared with females and non-White children, non-Hispanic White males are more likely to come to medical attention for short stature. Racially and ethnically diverse populations and males are underrepresented in studies of pubertal development and attainment of peak bone mass, with current norms based on European populations. Like adults, racial and ethnic minority youth suffer a higher burden of disease from obesity, T1D and T2D, and have less access to diabetes treatment technologies and bariatric surgery. LGBTQIA youth and adults also face discrimination and multiple barriers to endocrine care due to pathologizing sexual orientation and gender identity, lack of culturally competent care providers, and policies. Multilevel interventions to address these disparities are required. Inclusion of racial, ethnic, and LGBTQIA populations in longitudinal life course studies is needed to assess growth, puberty, and attainment of peak bone mass. Growth and development charts may need to be adapted to non-European populations. In addition, extension of these studies will be required to understand the clinical and physiologic consequences of interventions to address abnormal development in these populations. Health policies should be recrafted to remove barriers in care for children with obesity and/or diabetes and for LGBTQIA children and adults to facilitate comprehensive access to care, therapeutics, and technological advances. Public health interventions encompassing collection of accurate demographic and social needs data, including the intersection of social determinants of health with health outcomes, and enactment of population health level interventions will be essential tools.
Active Surveillance May Be the Best Initial Management for Papillary Thyroid Microcarcinoma
Authors: Ito Yasuhiro , Miyauchi Akira 
Published: May 2023

Abstract
Active surveillance for low-risk papillary thyroid microcarcinoma (PTMC; T1aN0MI) was initiated at Kuma Hospital (Kobe, Japan) in 1993, based on a proposal by Akira Miyauchi. Favorable outcomes of such surveillance have been reported. Our latest study revealed 5- and 10-year tumor enlargement rates (by ≥ 3 mm) of 3.0% and 5.5% and 5- and 10-year node metastasis appearance rates of 0.9% and 1.1%, respectively. The postoperative prognosis did not differ between patients who underwent immediate surgery and those who underwent conversion surgery after progression. These findings suggest that active surveillance may be the best initial management of PTMCs.
AI and machine learning ethics, law, diversity, and global impact
Authors: Drabiak Katherine , Kyzer Skylar , Nemov Valerie , El Naqa Issam 
Published: May 2023

Abstract
Artificial intelligence (AI) and its machine learning (ML) algorithms are offering new promise for personalized biomedicine and more cost-effective healthcare with impressive technical capability to mimic human cognitive capabilities. However, widespread application of this promising technology has been limited in the medical domain and expectations have been tampered by ethical challenges and concerns regarding patient privacy, legal responsibility, trustworthiness, and fairness. To balance technical innovation with ethical applications of AI/ML, developers must demonstrate the AI functions as intended and adopt strategies to minimize the risks for failure or bias. This review describes the new ethical challenges created by AI/ML for clinical care and identifies specific considerations for its practice in medicine. We provide an overview of regulatory and legal issues applicable in Europe and the United States, a description of technical aspects to consider, and present recommendations for trustworthy AI/ML that promote transparency, minimize risks of bias or error, and protect the patient well-being.
Prevalence of diabetes mellitus in patients undergoing coronary artery bypass grafting in a Tertiary Care Hospital
Authors: Bahauddin Khan  , Mujeeb Ur Rehman  , Mujahid Ul Islam  , Imtiaz Ahmad  
Published: May 2023

Objective: To find out the prevalence of diabetes mellitus in patients undergoing coronary artery bypass grafting (CABG).
Methods: This retrospective study was conducted in Northwest General Hospital and Research center Hayatabad, Peshawar over a duration of 15 months (December 2020 ― March 2022). Every patient was tested through regular laboratory investigations. Diabetes mellitus was established according to WHO standards of fasting plasma glucose >126 mg/dl or two hours postprandial glucose level of 200 mg/dl. Data were analyzed using SPSS. Mean and standard deviation was used for quantitative data. Frequency and percentages were used for qualitative data. Shapiro Wilk’s test was done to find the normality of the data.
Results: Out of a total of 360 candidates, 129 (36%) individuals were non-diabetic and 231 (64%) candidates were diabetic. Among the diabetic patients, 64 (28%) were female and 167 (72%) were males with a ratio of 1:2.6 respectively.
Conclusion: Prevalence of diabetes was 64% among the CABG population. Since the prevalence of diabetes can significantly affect the outcomes of people undergoing CABG, it is essential to generate awareness regarding diabetes among healthcare workers as well as the general population. More extensive research is needed to be carried by various health care centers to figure out the prevalence of diabetes mellitus in cardiac surgery patients.
doi: https://doi.org/10.12669/pjms.39.4.7250
How to cite this: Khan B, Mujeeb Ur Rehman, Mujahid Ul Islam, Ahmad I. Prevalence of diabetes mellitus in patients undergoing coronary artery bypass grafting in a Tertiary Care Hospital. Pak J Med Sci. 2023;39(4):---------. doi: https://doi.org/10.12669/pjms.39.4.7250
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Who’s to blame for central venous stenosis
Authors: Li Xiaodong , Liu Shuangyan 
Published: May 2023

doi: https://doi.org/10.12669/pjms.39.4.7559
How to cite this: Li X, Liu S. Who’s to blame for central venous stenosis. Pak J Med Sci. 2023;39(4):---------. doi: https://doi.org/10.12669/pjms.39.4.7559
Pseudo-teams in Healthcare: The Perils of Impersonating a Cohesive Unit
Authors: Lal Shankar , Khan Ehtesham 
Published: May 2023

Teamwork is a critical aspect of healthcare and is widely recognised as a cornerstone of effective patient care. However, not all healthcare teams are created equal, and some teams that appear to work well together on the surface are better described as pseudo-teams rather than true teams. This issue is frequently disregarded and overlooked despite its importance, yet it significantly impacts patient care and staff morale. We wish to describe the concept of pseudo teams in healthcare, their perils, and ways to create true teams characterised by shared goals, open communication, and a commitment to each other’s success.
doi: https://doi.org/10.12669/pjms.39.4.7665
How to cite this: Lal S, Khan E. Pseudo-teams in Healthcare: The Perils of Impersonating a Cohesive Unit. Pak J Med Sci. 2023;39(4):---------. doi: https://doi.org/10.12669/pjms.39.4.7665
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.