bluuebunny/crossref_metadata_2025_split huggingface dataset:
Describing the evidence-base for research engagement by health care providers and health care organisations: a scoping review
Authors: Yoong Sze Lin , Bolsewicz Katarzyna , Reilly Kathryn , Williams Christopher , Wolfenden Luke , Grady Alice , Kingsland Melanie , Finch Meghan , Wiggers John 
Published: January 2023

AbstractBackgroundHaving a research-engaged health and medical workforce is associated with improvements in clinical outcomes for patients. As such, there has been significant government investment internationally to support health care organisations and services to increase staff engagement with research.ObjectivesThis scoping review sought to provide an overview of the literature describing strategies employed to increase research engagement by health care providers and organisations, and to undertake a qualitative analysis to generate a list of research engagement strategies.MethodsA scoping review using systematic search strategies was undertaken to locate peer-review publications and grey literature related to research engagement by health care providers and organisations. Research engagement was defined as a ‘deliberate set of intellectual and practical activities undertaken by health care staff and organisations to conduct research’. A database search of electronic records was performed with no limit on publication date. Publications were included regardless of study type (excluding systematic reviews) and categorised as either databased (presenting data or new analysis of existing data) and non-databased (no new data or analyses). Databased publications were further classified according to study type, study design and setting. A qualitative synthesis using a Framework Approach was undertaken with all studies that described a strategy to improve research engagement.ResultsA total of 152 publications were included in this study with 54% categorised as non-databased. Of the databased articles, the majority (72%) were descriptive studies describing prevalence of correlates of research engagement, 17 (25%) described intervention studies where only two were controlled studies. The following research engagement strategies were identified: i) dual skilled team/staff, ii) resources or physical infrastructure, iii) incentives, iv) leadership support of research, v) education/training, vi) networks, vii) forming partnerships or collaborations and viii) overall leadership structure of entity.ConclusionsThe literature on research engagement is primarily opinion-based and descriptive in nature. To provide the evidence needed to inform strategies, this needs to progress beyond descriptive to more rigorous well-designed intervention research.
Pre-hyperglycemia immune cell trafficking underlies subclinical diabetic cataractogenesis
Authors: Ranaei Pirmardan Ehsan , Zhang Yuanlin , Barakat Aliaa , Naseri Marzieh , Russmann Christoph , Hafezi-Moghadam Ali 
Published: January 2023

Abstract
Background
This work elucidates the first cellular and molecular causes of cataractogenesis. Current paradigm presupposes elevated blood glucose as a prerequisite in diabetic cataractogenesis. Novel evidence in our model of diabetic cataract challenges this notion and introduces immune cell migration to the lens and epithelial-mesenchymal transformation (EMT) of lens epithelial cells (LECs) as underlying causes.

Methods
Paucity of suitable animal models has hampered mechanistic studies of diabetic cataract, as most studies were traditionally carried out in acutely induced hyperglycemic animals. We introduced diabetic cataract in the Nile grass rat (NGR) that spontaneously develops type 2 diabetes (T2D) and showed its closeness to the human condition. Specialized stereo microscopy with dual bright-field illumination revealed novel hyperreflective dot-like microlesions in the inner cortical regions of the lens. To study immune cell migration to the lens, we developed a unique in situ microscopy technique of the inner eye globe in combination with immunohistochemistry.

Results
Contrary to the existing paradigm, in about half of the animals, the newly introduced hyper reflective dot-like microlesions preceded hyperglycemia. Even though the animals were normoglycemic, we found significant changes in their oral glucose tolerance test (OGTT), indicative of the prediabetic stage. The microlesions were accompanied with significant immune cell migration from the ciliary bodies to the lens, as revealed in our novel in situ microscopy technique. Immune cells adhered to the lens surface, some traversed the lens capsule, and colocalized with apoptotic nuclei of the lens epithelial cells (LECs). Extracellular degradations, amorphous material accumulations, and changes in E-cadherin expressions showed epithelial-mesenchymal transformation (EMT) in LECs. Subsequently, lens fiber disintegration and cataract progression extended into cortical, posterior, and anterior subcapsular cataracts.

Conclusions
Our results establish a novel role for immune cells in LEC transformation and death. The fact that cataract formation precedes hyperglycemia challenges the prevailing paradigm that glucose initiates or is necessary for initiation of the pathogenesis. Novel evidence shows that molecular and cellular complications of diabetes start during the prediabetic state. These results have foreseeable ramifications for early diagnosis, prevention and development of new treatment strategies in patients with diabetes.
Activation of NLRP3 inflammasome in lung epithelial cells triggers radiation-induced lung injury
Authors: Rao Xinrui , Zhou Dong , Deng Huilin , Chen Yunshang , Wang Jian , Zhou Xiaoshu , Jie Xiaohua , Xu Yingzhuo , Wu Zilong , Wang Geng , Dong Xiaorong , Zhang Sheng , Meng Rui , Wu Chuangyan , Xing Shijie , Fan Kai , Wu Gang , Zhou Rui 
Published: January 2023

Abstract
Background
Radiation-induced lung injury (RILI) is the most common and serious complication of chest radiotherapy. However, reported radioprotective agents usually lead to radiation resistance in tumor cells. The key to solving this problem is to distinguish between the response of tumor cells and normal lung epithelial cells to radiation damage.

Methods
RNA-Seq was used to recognize potential target of alleviating the progression of RILI as well as inhibiting tumor growth. The activation of NLRP3 inflammasome in lung epithelial cells was screened by qRT-PCR, western blotting, immunofluorescence, and ELISA. An in vivo model of RILI and in vitro conditioned culture model were constructed to evaluate the effect of NLRP3/interleukin-1β on fibroblasts activation. ROS, ATP, and (NADP)+/NADP(H) level in lung epithelial cells was detected to explore the mechanism of NLRP3 inflammasome activation. The lung macrophages of the mice were deleted to evaluate the role of lung epithelial cells in RILI. Moreover, primary cells were extracted to validate the results obtained from cell lines.

Results
NLRP3 activation in epithelial cells after radiation depends on glycolysis-related reactive oxygen species accumulation. DPYSL4 is activated and acts as a negative regulator of this process. The NLRP3 inflammasome triggers interleukin-1β secretion, which directly affects fibroblast activation, proliferation, and migration, eventually leading to lung fibrosis.

Conclusions
Our study suggests that NLRP3 inflammasome activation in lung epithelial cells is essential for radiation-induced lung injury. These data strongly indicate that targeting NLRP3 may be effective in reducing radiation-induced lung injury in clinical settings.
The real-world safety profile of sodium-glucose co-transporter-2 inhibitors among older adults (≥ 75 years): a retrospective, pharmacovigilance study
Authors: Goldman Adam , Fishman Boris , Twig Gilad , Raschi Emanuel , Cukierman-Yaffe Tali , moshkovits Yonatan , Pomerantz Alon , Ben-Zvi Ilan , Dankner Rachel , Maor Elad 
Published: January 2023

AbstractBackgroundAs indications for sodium-glucose co-transporter-2 inhibitors (SGLT2i) are expanding, a growing number of older adults have become candidates for treatment. We studied the safety profile of SGLT2i among older adults.MethodsA retrospective, pharmacovigilance study of the FDA’s global database of safety reports. To assess reporting of pre-specified adverse events following SGLT2i among adults (< 75 years) and older adults (≥ 75), we performed a disproportionality analysis using the sex-adjusted reporting odds ratio (adj.ROR).ResultsWe identified safety reports of 129,795 patients who received non-insulin anti-diabetic drugs (NIAD), including 24,253 who were treated with SGLT2i (median age 60 [IQR: 51–68] years, 2,339 [9.6%] aged ≥ 75 years). Compared to other NIAD, SGLT2i were significantly associated with amputations (adj.ROR = 355.1 [95%CI: 258.8 − 487.3] vs adj.ROR = 250.2 [79.3 − 789.5]), Fournier gangrene (adj.ROR = 45.0 [34.5 − 58.8] vs adj.ROR = 88.0 [27.0 − 286.6]), diabetic ketoacidosis (adj.ROR = 32.3 [30.0 − 34.8] vs adj.ROR = 23.3 [19.2 − 28.3]), genitourinary infections (adj.ROR = 10.3 [9.4 − 11.2] vs adj.ROR = 8.6 [7.2 − 10.3]), nocturia (adj.ROR = 5.5 [3.7 − 8.2] vs adj.ROR = 6.7 [2.8 − 15.7]), dehydration (adj.ROR = 2.5 [2.3 − 2.8] vs adj.ROR = 2.6 [2.1 − 3.3]), and fractures (adj.ROR = 1.7 [1.4 − 2.1] vs adj.ROR = 1.5 [1.02 − 2.1]) in both adults and older adults, respectively. None of these safety signals was significantly greater in older adults (Pinteractionthreshold of 0.05). Acute kidney injury was associated with SGLT2i in adults (adj.ROR = 1.97 [1.85 − 2.09]) but not in older adults (adj.ROR = 0.71 [0.59 − 0.84]). Falls, hypotension, and syncope were not associated with SGLT2i among either adults or older adults.ConclusionIn this global post-marketing study, none of the adverse events was reported more frequently among older adults. Our findings provide reassurance regarding SGLT2i treatment in older adults, although careful monitoring is warranted.
Prenatal exposure to ambient air pollution is associated with neurodevelopmental outcomes at 2 years of age
Authors: Morgan Zachariah E. M. , Bailey Maximilian J. , Trifonova Diana I. , Naik Noopur C. , Patterson William B. , Lurmann Frederick W. , Chang Howard H. , Peterson Bradley S. , Goran Michael I. , Alderete Tanya L. 
Published: January 2023

Abstract
Background
Higher prenatal ambient air pollution exposure has been associated with impaired neurodevelopment in preschoolers and school-aged children. The purpose of this study was to explore the relationships between prenatal ambient air pollution exposure and neurodevelopment during infancy.

Methods
This study examined 161 Latino mother-infant pairs from the Southern California Mother’s Milk Study. Exposure assessments included prenatal nitrogen dioxide (NO2) and particulate matter smaller than 2.5 and 10 microns in diameter (PM2.5 and PM10, respectively). The pregnancy period was also examined as three windows, early, mid, and late, which describe the first, middle, and last three months of pregnancy. Infant neurodevelopmental outcomes at 2 years of age were measured using the Bayley-III Scales of Infant and Toddler Development. Multivariable linear models and distributed lag linear models (DLM) were used to examine relationships between prenatal exposures and neurodevelopmental scores, adjusting for socioeconomic status, breastfeeding frequency, time of delivery, pre-pregnancy body mass index, and infant birthweight and sex.

Results
Higher prenatal exposure to PM10 and PM2.5 was negatively associated with composite cognitive score (β = -2.01 [-3.89, -0.13] and β = -1.97 [-3.83, -0.10], respectively). In addition, higher average prenatal exposure to PM10 was negatively associated with composite motor (β = -2.35 [-3.95, -0.74]), scaled motor (β = -0.77 [-1.30, -0.24]), gross motor (β = -0.37 [-0.70, -0.04]), fine motor (β = -0.40 [-0.71, -0.09]), composite language (β = -1.87 [-3.52, -0.22]), scaled language (β = -0.61 [-1.18, -0.05]) and expressive communication scaled scores (β = -0.36 [-0.66, -0.05]). DLMs showed that higher prenatal air pollution exposure during mid and late pregnancy was inversely associated with motor, cognitive, and communication language scores.

Conclusions
Higher exposure to air pollutants during pregnancy, particularly in the mid and late prenatal periods, was inversely associated with scaled and composite motor, cognitive, and language scores at 2 years. These results indicate that prenatal ambient air pollution may negatively impact neurodevelopment in early life.
Molecular differences of angiogenic versus vessel co-opting colorectal cancer liver metastases at single-cell resolution
Authors: Fleischer Johannes Robert , Schmitt Alexandra Maria , Haas Gwendolyn , Xu Xingbo , Zeisberg Elisabeth Maria , Bohnenberger Hanibal , Küffer Stefan , Teuwen Laure-Anne , Karras Philipp Johannes , Beißbarth Tim , Bleckmann Annalen , Planque Mélanie , Fendt Sarah-Maria , Vermeulen Peter , Ghadimi Michael , Kalucka Joanna , De Oliveira Tiago , Conradi Lena-Christin 
Published: January 2023

Abstract
Background
Colorectal cancer liver metastases (CRCLM) are associated with a poor prognosis, reflected by a five-year survival rate of 14%. Anti-angiogenic therapy through anti-VEGF antibody administration is one of the limited therapies available. However, only a subgroup of metastases uses sprouting angiogenesis to secure their nutrients and oxygen supply, while others rely on vessel co-option (VCO). The distinct mode of vascularization is reflected by specific histopathological growth patterns (HGPs), which have proven prognostic and predictive significance. Nevertheless, their molecular mechanisms are poorly understood.

Methods
We evaluated CRCLM from 225 patients regarding their HGP and clinical data. Moreover, we performed spatial (21,804 spots) and single-cell (22,419 cells) RNA sequencing analyses to explore molecular differences in detail, further validated in vitro through immunohistochemical analysis and patient-derived organoid cultures.

Results
We detected specific metabolic alterations and a signature of WNT signalling activation in metastatic cancer cells related to the VCO phenotype. Importantly, in the corresponding healthy liver of CRCLM displaying sprouting angiogenesis, we identified a predominantly expressed capillary subtype of endothelial cells, which could be further explored as a possible predictor for HGP relying on sprouting angiogenesis.

Conclusion
These findings may prove to be novel therapeutic targets to the treatment of CRCLM, in special the ones relying on VCO.
North Carolina pharmacists’ willingness to sell fentanyl test strips: a survey study
Authors: Marley Grace T. , Ostrach Bayla , Carpenter Delesha 
Published: January 2023

Abstract
Background
Although fentanyl test strips (FTS) can accurately determine the presence of fentanyl in unregulated substances, access to FTS remains limited. This study aimed to examine North Carolina community pharmacists’ attitudes and willingness to engage in various behaviors related to FTS sales and distribution.

Methods
A convenience sample of community pharmacists completed an online survey that assessed: (1) comfort initiating an FTS conversation; (2) willingness to sell FTS, distribute FTS instructions, counsel on FTS, refer patients to harm reduction organizations, and advertise FTS; (3) perceived barriers and benefits of selling FTS; and (4) interest in FTS training. Data were collected from March to May 2022. Descriptive statistics were calculated.

Results
Of the 592 pharmacists who participated, most were somewhat or very willing to refer patients to harm reduction organizations for FTS (514, 86.9%), counsel on FTS (485, 81.9%), distribute FTS instructions (475, 80.2%), sell FTS (470, 79.3%), and advertise FTS for sale (372, 62.9%). The most commonly reported benefits of selling FTS were reducing overdose deaths in the community (n = 482, 81.4%) and participating in community harm reduction efforts (n = 455; 76.9%). Barriers commonly reported to selling FTS were: not knowing where to order FTS (n = 295, 49.8%) and discomfort initiating a conversation about FTS (n = 266, 44.9%). Most respondents (88.3%) were interested in FTS training.

Conclusion
North Carolina community pharmacists are willing to engage in various behaviors related to FTS sales and distribution. Most pharmacists were interested in receiving FTS training, which should be created to address pharmacist-reported barriers to FTS sales. Pharmacist distribution of FTS could increase access to FTS at the community level and has the potential to change drug use behavior and reduce overdose deaths.
Interpersonal violence and recurrent headache among adolescents with a history of psychiatric problems
Authors: Greger Hanne Klæboe , Kristianslund Sara Konstanse , Stensland Synne Øien 
Published: January 2023

Abstract
Background
Interpersonal violence (IPV) is found to be associated with mental health problems and pain disorders such as headache among children and adolescents. It is well-known that adolescents in need of mental health services have experienced IPV more often than adolescents in the general population. However, there has not been much focus on pain conditions in child and adolescent psychiatric populations.

Methods
Data from the current study are based on a 3-year follow-up of the CAP-survey, which is a study of adolescents in the child and adolescent psychiatric unit population of St. Olavs Hospital (Trondheim University Hospital). The baseline study was conducted between 2009 and 2011, with 717 participants between 13 and 18 years. All participants were enrolled, or newly referred to the child and adolescent psychiatric clinic. At follow-up, 570 participants completed questionnaire, and 550 completed a diagnostic interview. The participants were aged 16–21 years (mean age 18.6 years).

Results
A third of the adolescents reported frequent headaches (weekly or daily). Adolescents with more severe mental problems were more likely to experience frequent headaches. Adolescents exposed to unpleasant sexual acts or bullying, reported more frequent headaches than non-exposed participants. Participants exposed to three or more types of IPV seemed to be at particularly high risk of experiencing frequent headache.

Conclusions
Both experiences of interpersonal violence and headache are common in this clinical psychiatric population. Clinicians should assess for headache disorders in addition to psychiatric and trauma assessment and provide need-based treatment to enhance chance of recovery among adolescents in mental health services.
Association between COVID-19 risk-mitigation behaviors and specific mental disorders in youth
Authors: Conway Kevin P. , Bhardwaj Kriti , Michel Emmanuella , Paksarian Diana , Nikolaidis Aki , Kang Minji , Merikangas Kathleen R. , Milham Michael P. 
Published: January 2023

Abstract
Background
Although studies of adults show that pre-existing mental disorders increase risk for COVID-19 infection and severity, there is limited information about this association among youth. Mental disorders in general as well as specific types of disorders may influence the ability to comply with risk-mitigation strategies to reduce COVID-19 infection and transmission.

Methods
Youth compliance (rated as “Never,” “Sometimes,” “Often,” or “Very often/Always”) with risk mitigation was reported by parents on the CoRonavIruS Health Impact Survey (CRISIS) in January 2021. The sample comprised 314 female and 514 male participants from the large-scale Child Mind Institute Healthy Brain Network, a transdiagnostic self-referred, community sample of children and adolescents (ages 5–21). Responses were summarized using factor analysis of risk mitigation, and their associations with lifetime mental disorders (assessed via structured diagnostic interviews) were identified with linear regression analyses (adjusted for covariates). All analyses used R Project for Statistical Computing for Mac (v.4.0.5).

Results
A two-factor model was the best-fitting solution. Factor 1 (avoidance behaviors) included avoiding groups, indoor settings, and other peoples’ homes; avoidance scores were higher among youth with any anxiety disorder (p = .01). Factor 2 (hygiene behaviors) included using hand sanitizer, washing hands, and maintaining social distance; hygiene scores were lower among youth with ADHD (combined type) (p = .02). Mask wearing was common (90%), did not load on either factor, and was not associated with any mental health disorder.

Conclusion and relevance
Although most mental disorders examined were not associated with risk mitigation, youth with ADHD characterized by hyperactivity plus inattention may need additional support to consistently engage in risk-mitigation behaviors. Enhancing risk-mitigation strategies among at-risk groups of youth may help reduce COVID-19 infection and transmission.
LARP6 suppresses colorectal cancer progression through ZNF267/SGMS2-mediated imbalance of sphingomyelin synthesis
Authors: Long Xiaoli , Liu Xunhua , Deng Ting , Chen Jianxiong , Lan Jiawen , Zhang Sijing , Zhou Miao , Guo Dan , Zhou Jun 
Published: January 2023

AbstractBackgroundWith increasing incidence and mortality, colorectal cancer (CRC) seriously endangers human health.LARP6, a member of La-related protein (LARP) family, is a RNA binding protein and probably associates with CRC progression, but its specific roles and mechanisms in CRC still remain unknown.MethodQuantitative real-time PCR (qPCR), western blot, and immunohistochemistry were employed to examine LARP6 expression in CRC tissues. Using the stableLARP6overexpression or interference CRC cell lines, the effect of LARP6 on CRC progression were evaluated. High-throughput RNA immunoprecipitation sequencing (RIP-seq) and a series of relevant experiments were conducted to explain how LARP6 functions. SPSS software was used for statistical analysis.ResultIn this study, we found thatLARP6expression is downregulated in CRC and correlates with patients’ overall survival and relapse-free survival. Furthermore, altered LARP6 expression influences CRC cells invasion and metastasis. Mechanically, we discovered that LARP6 bindZNF267mRNA and regulated its stability and translation. LARP6 inhibited expression ofSGMS2, a downstream target of ZNF267, resulting in ceramide and sphingomyelin imbalance in CRC cells. Interestingly, LARP6 also enhances autophagy activity of CRC cells, and the effect was at least partially determined by the inhibition of SGMS2-mediated sphingomyelin synthesis.ConclusionOur study showed howLARP6/ZNF267/SGMS2axis influence CRC progression, which contributes to further understanding of the molecular mechanisms underlying CRC development.