bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ononin ameliorates inflammation and cartilage degradation in rat chondrocytes with IL-1β-induced osteoarthritis by downregulating the MAPK and NF-κB pathways
Authors: Xu Fang , Zhao Liang-Jun , Liao Ting , Li Zhao-Cong , Wang Lei-Lei , Lin Pan-Yu , Jiang Rui , Wei Qing-Jun 
Published: January 2022

Abstract
Background
Osteoarthritis (OA) treatment aims to improve inflammation and delay cartilage degeneration. However, there is no effective strategy presently available. Ononin, a representative isoflavone glycoside component extracted from natural Chinese herbs, exerts anti-inflammatory and proliferative effects. However, the therapeutic effect of ononin on chondrocyte inflammation remains unclear.

Methods
In this study, we explored the therapeutic effect and potential mechanism of ononin in OA by establishing an interleukin-1 beta (IL-1β)-induced chondrocyte inflammation model.

Results
Our results verified that ononin alleviated the IL-1β-induced decrease in chondrocyte viability, attenuated the overexpression of the inflammatory factors tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and simultaneously inhibited the expression of cartilage extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteinase-13 (MMP-13). Furthermore, the decomposition of Collagen II protein could be alleviated in the OA model by ononin. Finally, ononin improved chondrocyte inflammation by downregulating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signalling pathways.

Conclusion
Our findings suggested that ononin could inhibit the IL-1β-induced proinflammatory response and ECM degradation in chondrocytes by interfering with the abnormal activation of the MAPK and NF-κB pathways, indicating its protective effect against OA.
Creating a win-win for the health system and health Profession’s education: a direct observation clinical experience with feedback iN real-time (DOCENT) for low acuity patients in the emergency department
Authors: Clay Alison S. , Leiman Erin R. , Theiling Brent Jason , Song Yao , Padilla Blanca Blanca Iris , Hudak Nicholas M. , Hartman Ann Michelle , Hoder Jeffrey M. , Waite Kathleen A. , Lee Hui-Jie , Buckley Edward G. 
Published: January 2022

Abstract
Background
Clinical education across the professions is challenged by a lack of recognition for faculty and pressure for patient throughput and revenue generation. These pressures may reduce direct observation of patient care provided by students, a requirement for both billing student-involved services and assessing competence. These same pressures may also limit opportunities for interprofessional education and collaboration.

Methods
An interprofessional group of faculty collaborated in a sequential quality improvement project to identify the best patients and physical location for a student teaching clinic. Patient chief complaint, use of resources, length of stay, estimated severity of illness and student participation and evaluation of the clinic was tracked.

Results

Clinic Optimization and Patient Care: Five hundred and thirty-two emergency department (ED) patients were seen in the first 19 months of the clinic. A clinic located near the ED allowed for patients with higher emergency severity index and greater utilization of imaging. Patients had similar or lower lengths of stay and higher satisfaction than patients who remained in the ED (p < 0.0001). In the second clinic location, from October 2016–June 2019, 644 patients were seen with a total of 667 concerns; the most common concern was musculoskeletal (50.1%).

Student Interprofessional Experience: A total of 991 students participated in the clinic: 68.3% (n = 677) medical students, 10.1% (n = 100) physician assistant students, 9.7% (n = 96) undergraduate nursing students, 9.1% (n = 90) physical therapy students, and 2.8% (n = 28) nurse practitioner students. The majority (74.5%, n = 738) of student participants worked with students from other professions. More than 90% of students reported that faculty set a positive learning environment respectful of students. However, 20% of students reported that faculty could improve provision of constructive feedback.

Direct Observation: Direct observation of core entrustable professional activities for medical students was possible. Senior medical students were more likely to be observed generating a differential diagnosis or management plan than first year medical students.

Conclusions
Creation of a DOCENT clinic in the emergency department provided opportunities for interprofessional education and observation of student clinical skills, enriching student experience without compromising patient care.
Modernising physician resource planning: a national interactive web platform for Canadian medical trainees
Authors: Bourcier D. , Collins B. W. , Tanya S. M. , Basu M. , Sayal A. P. , Moolla S. , Dong A. , Balas M. , Molcak H. , Punchhi G. 
Published: January 2022

AbstractBackgroundHealthcare systems rely heavily upon human resources to ensure high-quality access to care for the general population. With significant health worker shortages predicted worldwide in the coming decades, maximizing the current workforce by means of a physician resource planning (PRP) strategy that ensures the right number, mix, and distribution of physicians to meet population needs is warranted. In Canada, there is an insufficient number of primary care providers, and disproportionately low numbers of specialist physicians in rural compared to urban regions. Currently, Canadian medical students are not effectively included in PRP strategy and lack the required information for career orientation to help rebalance the population’s workforce needs. This paper present theHealth Human Resource (HHR) Platform, a comprehensive web tool that includes relevant workforce data to empower medical students in choosing a discipline based on both personal interests and social accountability.ResultsPhysician workforce data, comments from Canadian residency program directors, and career planning resources were collected by the Canadian Federation of Medical Student’s (CFMS) HHR Task Force. This information was consolidated to create a national interactive platform that uses a map, comparison table, and trend graphs to illustrate over 500,000 unique data points from 37 datasets, including specific information and resources spanning 62 medical specialties from 2015 onwards. There was a 24.6% response rate for program director comments. During the first 4 months of theHHR Platformlaunch, there were 2434 different users, of which 985 were returning, with an average of 20.0 users per day spending on average 3 min on the platform.ConclusionsTheHHR Platformconstitutes a national approach to PRP informing medical students on the mix and distribution of physicians needed to meet the future healthcare demands of the Canadian population.
Human placental mesenchymal stromal cells are ciliated and their ciliation is compromised in preeclampsia
Authors: Romberg Sophia Indira , Kreis Nina-Naomi , Friemel Alexandra , Roth Susanne , Souto Alice Steglich , Hoock Samira Catharina , Fischer Kyra , Nowak Thorsten , Solbach Christine , Louwen Frank , Ritter Andreas , Yuan Juping 
Published: January 2022

Abstract
Background
The development of the human placenta is tightly coordinated by a multitude of placental cell types, including human chorionic villi mesenchymal stromal cells (hCV-MSCs). Defective hCV-MSCs have been reported in preeclampsia (PE), a gestational hypertensive disease characterized by maternal endothelial dysfunction and systemic inflammation. Our goal was to determine whether hCV-MSCs are ciliated and whether altered ciliation is responsible for defective hCV-MSCs in preeclamptic placentas, as the primary cilium is a hub for signal transduction, which is important for various cellular activities.

Methods
In the present work, we collected placental tissues from different gestational stages and we isolated hCV-MSCs from 1st trimester, term control, and preeclamptic placentas. We studied their ciliation, functionality, and impact on trophoblastic cell lines and organoids formed from human trophoblast stem cells (hTSCs) and from the trophoblastic cell line JEG-3 with various cellular and molecular methods, including immunofluorescence staining, gene analysis, spheroid/organoid formation, motility, and cellular network formation assay. The statistical evaluation was performed using a Student’s t test (two-tailed and paired or homoscedastic) or an unpaired Mann–Whitney U test (two-tailed).

Results
The results show that primary cilia appeared abundantly in normal hCV-MSCs, especially in the early development of the placenta. Compared to control hCV-MSCs, the primary cilia were truncated, and there were fewer ciliated hCV-MSCs derived from preeclamptic placentas with impaired hedgehog signaling. Primary cilia are necessary for hCV-MSCs’ proper signal transduction, motility, homing, and differentiation, which are impaired in preeclamptic hCV-MSCs. Moreover, hCV-MSCs derived from preeclamptic placentas are significantly less capable of promoting growth and differentiation of placental organoids, as well as cellular network formation.

Conclusions
These data suggest that the primary cilium is required for the functionality of hCV-MSCs and primary cilia are impaired in hCV-MSCs from preeclamptic placentas.
Healthy lifestyle, metabolomics and incident type 2 diabetes in a population-based cohort from Spain
Authors: Delgado-Velandia Mario , Gonzalez-Marrachelli Vannina , Domingo-Relloso Arce , Galvez-Fernandez Marta , Grau-Perez Maria , Olmedo Pablo , Galan Iñaki , Rodriguez-Artalejo Fernando , Amigo Nuria , Briongos-Figuero Laisa , Redon Josep , Martin-Escudero Juan Carlos , Monleon-Salvado Daniel , Tellez-Plaza Maria , Sotos-Prieto Mercedes 
Published: January 2022

Abstract
Background
The contribution of metabolomic factors to the association of healthy lifestyle with type 2 diabetes risk is unknown. We assessed the association of a composite measure of lifestyle with plasma metabolite profiles and incident type 2 diabetes, and whether relevant metabolites can explain the prospective association between healthy lifestyle and incident type 2 diabetes.

Methods
A Healthy Lifestyle Score (HLS) (5-point scale including diet, physical activity, smoking status, alcohol consumption and BMI) was estimated in 1016 Hortega Study participants, who had targeted plasma metabolomic determinations at baseline examination in 2001–2003, and were followed-up to 2015 to ascertain incident type 2 diabetes.

Results
The HLS was cross-sectionally associated with 32 (out of 49) plasma metabolites (2.5% false discovery rate). In the subset of 830 participants without prevalent type 2 diabetes, the rate ratio (RR) and rate difference (RD) of incident type 2 diabetes (n cases = 51) per one-point increase in HLS was, respectively, 0.69 (95% CI, 0.51, 0.93), and − 8.23 (95% CI, − 16.34, − 0.13)/10,000 person-years. In single-metabolite models, most of the HLS-related metabolites were prospectively associated with incident type 2 diabetes. In probit Bayesian Kernel Machine Regression, these prospective associations were mostly driven by medium HDL particle concentration and phenylpropionate, followed by small LDL particle concentration, which jointly accounted for ~ 50% of the HLS-related decrease in incident type 2 diabetes.

Conclusions
The HLS showed a strong inverse association with incident type 2 diabetes, which was largely explained by plasma metabolites measured years before the clinical diagnosis.
Explaining variable effects of an adaptable implementation package to promote evidence-based practice in primary care: a longitudinal process evaluation
Authors: Glidewell Liz , Hunter Cheryl , Ward Vicky , McEachan Rosemary R. C. , Lawton Rebecca , Willis Thomas A. , Hartley Suzanne , Collinson Michelle , Holland Michael , Farrin Amanda J. , Foy Robbie ,   on behalf of the ASPIRE programme team, Alderson Sarah , Carder Paul , Clamp Susan , West Robert , Rathfelder Martin , Hulme Claire , Richardson Judith , Stokes Tim , Watt Ian 
Published: January 2022

Abstract
Background
Implementing evidence-based recommendations is challenging in UK primary care, especially given system pressures and multiple guideline recommendations competing for attention. Implementation packages that can be adapted and hence applied to target multiple guideline recommendations could offer efficiencies for recommendations with common barriers to achievement. We developed and evaluated a package of evidence-based interventions (audit and feedback, educational outreach and reminders) incorporating behaviour change techniques to target common barriers, in two pragmatic trials for four “high impact” indicators: risky prescribing; diabetes control; blood pressure control; and anticoagulation in atrial fibrillation. We observed a significant, cost-effective reduction in risky prescribing but there was insufficient evidence of effect on the other outcomes. We explored the impact of the implementation package on both social processes (Normalisation Process Theory; NPT) and hypothesised determinants of behaviour (Theoretical Domains Framework; TDF).

Methods
We conducted a prospective multi-method process evaluation. Observational, administrative and interview data collection and analyses in eight primary care practices were guided by NPT and TDF. Survey data from trial and process evaluation practices explored fidelity.

Results
We observed three main patterns of variation in how practices responded to the implementation package. First, in integration and achievement, the package “worked” when it was considered distinctive and feasible. Timely feedback directed at specific behaviours enabled continuous goal setting, action and review, which reinforced motivation and collective action. Second, impacts on team-based determinants were limited, particularly when the complexity of clinical actions impeded progress. Third, there were delivery delays and unintended consequences. Delays in scheduling outreach further reduced ownership and time for improvement. Repeated stagnant or declining feedback that did not reflect effort undermined engagement.

Conclusions
Variable integration within practice routines and organisation of care, variable impacts on behavioural determinants, and delays in delivery and unintended consequences help explain the partial success of an adaptable package in primary care.
Phentermine–topiramate extended release for the dual treatment of obesity and sleep-related eating disorder: a case report
Authors: Grunvald Eduardo , DeConde Jennifer 
Published: January 2022

Abstract
Background
Obesity and eating disorders can present together, and pose diagnostic and therapeutic challenges to the clinician. Generally, lifestyle interventions alone for the treatment of obesity have modest long-term effectiveness. Phentermine–topiramate extended release is a relatively new medication approved for weight reduction. Sleep-related eating disorder is a rare condition that is often underdiagnosed. Both conditions are chronic and require long-term management. There is no definitive treatment for sleep-related eating disorder, and therapeutic options are based on case reports.

Case presentation
A 35-year-old Caucasian male with a body mass index of 41.7 kg/m2 presented for obesity treatment. History revealed nocturnal episodes of hyperphagia associated with amnesia of overeating and other features of sleep-related eating disorder. Treatment was initiated with phentermine–topiramate extended release. Five months later he lost 5% of his body weight and demonstrated resolution of sleep-related eating disorder behaviors. He reported no adverse side effects. Upon self-discontinuation of the medication, his eating disorder recurred.

Conclusions
Clinicians intending to help patients reduce body weight should screen for nocturnal eating and other eating disorders. Sleep-related eating disorder can be associated with significant morbidity and excess weight. Patients report adverse effects on quality of life as a result. Phentermine–topiramate extended release may be a good therapeutic option for patients presenting with comorbid obesity and sleep-related eating disorder. More research is needed to explore the efficacy and safety in this patient population.
Inhalable antibiotic resistomes emitted from hospitals: metagenomic insights into bacterial hosts, clinical relevance, and environmental risks
Authors: Wu Dong , Jin Ling , Xie Jiawen , Liu Hang , Zhao Jue , Ye Dan , Li Xiang-dong 
Published: January 2022

AbstractBackgroundThreats of antimicrobial resistance (AMR) to human health are on the rise worldwide. Airborne fine particulate matter (PM2.5), especially those emitted from hospitals, could serve as a substantial yet lesser-known environmental medium of inhalable antibiotic resistomes. A genome-centric understanding of the hosting bacterial taxa, mobility potential, and consequent risks of the resistomes is needed to reveal the health relevance of PM2.5-associated AMR from clinical settings.ResultsCompared to urban ambient air PM2.5, the hospital samples harbored nearly twice the abundance of antibiotic resistantance genes (ARGs, ~ 0.2 log10(ARGs/16S rRNA gene)) in the summer and winter sampled. The profiled resistome was closely correlated with the human-source-influenced (~ 30% of the contribution) bacterial community (Procrustes test,P< 0.001), reflecting the potential antibiotic-resistant bacteria (PARB), such as the human commensalsStaphylococcusspp. andCorynebacteriumspp. Despite the reduced abundance and diversity of the assembled metagenomes from summer to winter, the high horizontal transfer potential of ARGs, such as the clinically relevantblaOXAandbacA, in the human virulent PARB remained unaffected in the hospital air PM samples. The occurring patterns of β-lactam resistance genes and their hosting genomes in the studied hospital-emitting PM2.5were closely related to the in-ward β-lactam-resistant infections (SEM, std = 0.62,P< 0.01). Featured with more abundant potentially virulent PARB (2.89 genome copies/m3-air), the hospital samples had significantly higher resistome risk index scores than the urban ambient air samples, indicating that daily human exposure to virulent PARB via the inhalation of PM2.5was ten times greater than from the ingestion of drinking water.ConclusionsThe significance of AMR in the studied hospital-emitting PM2.5was highlighted by the greater abundance of ARGs, the prevalence of potentially virulent PARB, and the close association with hospital in-ward β-lactam infections. A larger-scale multi-source comparison of genome-resolved antibiotic resistomes is needed to provide a more holistic understanding to evaluate the importance of airborne AMR from the “One-Health” perspective.
Targeting interleukin-1β and inflammation in lung cancer
Authors: Zhang Jun , Veeramachaneni Nirmal 
Published: January 2022

AbstractInflammation is a process that protects organs against various potentially harmful stimuli and enables repair. Dysregulated inflammation, however, damages tissues and leads to disease, including cancer. Cancer-related inflammation is characterized by cytokine production, leukocyte infiltration, angiogenesis, and tissue remodeling—all critical processes in modulating the tumor microenvironment (TME). The TME is known to play a key role in tumor progression, and targeting its immune component to achieve a better anti-tumor response is the basis of immunotherapy. Despite the critical role cytokines play in the TME and tumor progression, there is currently only one therapy approved by the FDA that directly involves cytokine signaling: human recombinant interleukin-2 protein, aldesleukin. The recent Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS) trial evaluated the use of anti-interleukin-1β therapy in atherosclerotic disease; however, it also revealed interleukin-1β (IL-1β) blockade with canakinumab led to a significantly lower incidence of lung cancer. This has opened a promising new avenue for lung cancer therapy, and strategies using anti-IL-1β therapy alone or in combination with chemotherapy and/or immune checkpoint blockade are currently being evaluated in several clinical trials.
Long-term management of recurrent papillary thyroid carcinoma treated with lenvatinib for over 5 years: a case report
Authors: Imai Tsuneo , Kobayashi Hironobu , Senaha Tetsu , Imaizumi Toshiaki , Murata Yoshiharu 
Published: January 2022

Abstract
Background
Few reports exist of the long-term management of recurrent and progressive papillary thyroid carcinoma (PTC) with a tyrosine kinase inhibitor for over 5 years.

Case presentation
A 57-year-old woman was referred to a psychiatric hospital for the treatment of schizophrenia. The patient had been diagnosed with a PTC at the age of 40 and subsequently underwent a left thyroid lobectomy. At 47, completion total thyroidectomy and lymph node dissection were performed and the patient assessed as radioactive iodine refractory postoperatively. External radiation therapy was performed for Rouviere lymph nodes. At 57, neck and mediastinal lymph nodes, and lung metastases had progressed, and the trachea became narrowed by para-tracheal lymph node compression. After 2 weeks of sorafenib therapy on an outpatient basis, the patient was discovered unconsciousness at home and transferred to hospital by ambulance; sorafenib therapy was stopped. The patient was diagnosed with reversible posterior leukoencephalopathy syndrome by brain magnetic resonance imaging. External radiation therapy to the site of the tracheal stenosis in the neck and mediastinum was performed. The patient’s mental symptoms worsened, and she was referred to a psychiatric hospital, Kachi Memorial Hospital, in July 2015. In September, the patient’s mental state stabilized and in November, after computed tomography revealed rapid disease progression, lenvatinib was commenced at a daily dose of 24 mg. Measurable solid recurrence sites were neck lymph nodes in the pre-laryngeal subcutaneous space, right lobe of the lung, and left adrenal. After 3 months, the tumors shrank in a partial response (PR). Because of several adverse events, occasional dose reductions or discontinuations of lenvatinib were sometimes necessary. Since re-starting lenvatinib, treatment with this for 51 consecutive months was achieved while maintaining a PR. Although a new bone metastasis was noted after 57 months of lenvatinib, treatment was continued for another 9 months. The patient subsequently passed away in June 2021.

Conclusions
The long-term treatment of recurrent PTC with lenvatinib was feasible, with manageable adverse events, for more than 5 years.