Miracle-dz/UniFAR-FTUs huggingface dataset:
Patellofemoral joint loading and early osteoarthritis after ACL reconstruction

Patellofemoral joint (PFJ) osteoarthritis is common following anterior cruciate ligament reconstruction (ACLR) and may be linked with altered joint loading. However, little is known about the cross‐sectional and longitudinal relationship between PFJ loading and osteoarthritis post‐ACLR. This study tested if altered PFJ loading is associated with prevalent and worsening early PFJ osteoarthritis post‐ACLR. Forty‐six participants (mean ± 1 SD age 26 ± 5 years) approximately 1‐year post‐ACLR underwent magnetic resonance imaging (MRI) and biomechanical assessment of their reconstructed knee. Trunk and lower‐limb kinematics plus ground reaction forces were recorded during the landing phase of a standardized forward hop. These data were input into a musculoskeletal model to calculate the PFJ contact force. Follow‐up MRI was completed on 32 participants at 5‐years post‐ACLR. Generalized linear models (Poisson regression) assessed the relationship between PFJ loading and prevalent early PFJ osteoarthritis (i.e., presence of a PFJ cartilage lesion at 1‐year post‐ACLR) and worsening PFJ osteoarthritis (i.e., incident/progressive PFJ cartilage lesion between 1‐ and 5‐years post‐ACLR). A lower peak PFJ contact force was associated with prevalent early PFJ osteoarthritis at 1‐year post‐ACLR (n = 14 [30.4%]; prevalence ratio: 1.37; 95% confidence interval [CI]: 1.02–1.85) and a higher risk of worsening PFJ osteoarthritis between 1‐ and 5‐years post‐ACLR (n = 9 [28.1%]; risk ratio: 1.55, 95% CI: 1.13–2.11). Young adults post‐ACLR who exhibited lower PFJ loading during hopping were more likely to have early PFJ osteoarthritis at 1‐year and worsening PFJ osteoarthritis between 1‐ and 5‐years. Clinical interventions aimed at mitigating osteoarthritis progression may be beneficial for those with signs of lower PFJ loading post‐ACLR.
Seeing what is behind the smokescreen: A systematic review of methodological aspects of smoking interaction studies over the last three decades and implications for future clinical trials

Smoking drug interaction studies represent a common approach for the clinical investigation of CYP1A2 induction. Despite this important role, they remain an “orphan topic” in the existing regulatory framework of drug interaction studies, and important methodological aspects remain unaddressed. The University of Washington Drug Interaction Database (DIDB) was used to systematically review the published literature on dedicated smoking pharmacokinetic interaction studies in healthy subjects (1990 to 2021, inclusive). Various methodological aspects of identified studies were reviewed. A total of 51 studies met all inclusion criteria and were included in the analysis. Our review revealed that methods applied in smoking interaction studies are heterogeneous and often fall short of established methodological standards of other interaction trials. Methodological deficiencies included incomplete description of study populations, poor definition and lack of objective confirmation of smoker and nonsmoker characteristics, under‐representation of female subjects, small sample sizes, frequent lack of statistical sample size planning, frequent lack of use of existing markers of nicotine exposure and CYP1A2 activity measurements, and frequent lack of control of extrinsic CYP1A2 inducing or inhibiting factors. The frequent quality issues in the assessment and reporting of smoking interaction trials identified in this review call for a concerted effort in this area, if the results of these studies are meant to be followed by actionable decisions on dose optimization, when needed, for the effects of smoking on CYP1A2 victim drugs in smokers.
Proresolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis

Rheumatoid arthritis (RA) is a debilitating disease characterized by persistent accumulation of leukocytes within the articular cavity and synovial tissue. Metabololipidomic profiling of arthritic joints from omega-3 supplemented mice identified elevated levels of specialized proresolving lipid mediators (SPM) including resolvin D1 (RvD1). Profiling of human RA synovial fluid revealed physiological levels of RvD1, which — once applied to human neutrophils — attenuated chemotaxis. These results prompted analyses of the antiarthritic properties of RvD1 in a model of murine inflammatory arthritis. The stable epimer 17R-RvD1 (100 ng/day) significantly attenuated arthritis severity, cachexia, hind-paw edema, and paw leukocyte infiltration and shortened the remission interval. Metabololipidomic profiling in arthritic joints revealed 17R-RvD1 significantly reduced PGE 2 biosynthesis, while increasing levels of protective SPM. Molecular analyses indicated that 17R-RvD1 enhanced expression of genes associated with cartilage matrix synthesis, and direct intraarticular treatment induced chondroprotection. Joint protective actions of 17R-RvD1 were abolished in RvD1 receptor–deficient mice termed ALX/fpr2/3 −/− . These investigations open new therapeutic avenues for inflammatory joint diseases, providing mechanistic substance for the benefits of omega-3 supplementation in RA. In the present study, we performed lipid mediator metabololipidomics on arthritic joints from mice fed standard versus omega-3–enriched chow to directly compare the local bioactive lipid mediator metabolome. Among the mediators quantified, we identified elevated levels of RvD1, which was also identified in human RA synovial fluids. When its 17R epimer (selected for its increased metabolic stability, ref. 11) was administered to mice during inflammatory arthritis, it significantly reduced joint inflammation. Herein, we report mechanisms of action of RvD1 and tested its antiarthritic potential in an inflammatory polyarthritis model evoked by transfer of arthritogenic serum that mimics the presentation and histopathology of human RA. concentration range for physiological activities. Thus, when we tested the stable epimer 17R-RvD1 (11), a selective modulation of local lipid mediator biosynthesis and reduction in joint leukocyte infiltration was observed paralleled by macroscopic amelioration of arthritis severity, cachexia, and hind-paw edema. We also uncovered tissue-protective functions of 17R-RvD1, such as stimulation of chondrocyte matrix production and protection from cartilage degradation. Together, these findings identify 17R-RvD1 as a prototype for new therapeutic approaches for the treatment of arthritis.
Correlates of chronic hepatitis B virus infection in the general adult population of China: Systematic review and meta‐analysis

Chronic infection with hepatitis B virus (HBV) is a significant public health issue in China. Understanding factors associated with chronic HBV is important to enable targeted screening and education and to improve early diagnosis and prevention of disease progression. This systematic review and meta‐analysis aimed to identify and describe correlates of chronic HBV among Chinese adults. Searches were conducted in MEDLINE, EMBASE and grey literature up to 25 June 2020. Eligible papers included observational studies in adults of the general population in China that reported factors associated with chronic HBV, measured by Hepatitis B surface antigen (HBsAg). Meta‐analysis was performed using fixed‐effect models of HBsAg prevalence among factors, and of adjusted odds ratios (ORs) for chronic HBV associated with each factor. Overall 39 articles were included, covering 22 factors, including a range of sociodemographic, behavioural and medical factors. In meta‐analysis of eligible studies, a range of factors were significantly associated with higher HBsAg prevalence, including middle age, male sex, being married, rural residence, lower education, smoking, having a HBsAg positive household contact, family history of HBV, history of surgery or blood transfusion. The adjusted ORs varied, from 1.11 (95% CI 1.05–1.18) for smoking to 5.13 (95% CI 4.99–5.26) for having a HBsAg positive household contact. In Chinese adults, a range of factors are associated with chronic HBV infection, which may help inform targeted screening in the general population.
Modelling interval data with Normal and Skew-Normal distributions

A parametric modelling for interval data is proposed, assuming a multivariate Normal or Skew-Normal distribution for the midpoints and log-ranges of the interval variables. The intrinsic nature of the interval variables leads to special structures of the variance–covariance matrix, which is represented by five different possible configurations. Maximum likelihood estimation for both models under all considered configurations is studied. The proposed modelling is then considered in the context of analysis of variance and multivariate analysis of variance testing. To access the behaviour of the proposed methodology, a simulation study is performed. The results show that, for medium or large sample sizes, tests have good power and their true significance level approaches nominal levels when the constraints assumed for the model are respected; however, for small samples, sizes close to nominal levels cannot be guaranteed. Applications to Chinese meteorological data in three different regions and to credit card usage variables for different card designations, illustrate the proposed methodology.
Enhanced Recovery After Surgery Program and Opioid Consumption in Pulmonary Resection Surgery: A Retrospective Observational Study

BACKGROUND: Pulmonary resection surgery causes severe postoperative pain and usually requires opioid-based analgesia, particularly in the early postoperative period. However, the administration of large amounts of opioids is associated with various adverse events. We hypothesized that patients who underwent pulmonary resection under an enhanced recovery after surgery (ERAS) program consumed fewer opioids than patients who received conventional treatment. METHODS: A total of 2147 patients underwent pulmonary resection surgery between August 2019 and December 2020. Two surgeons (25%) at our institution implemented the ERAS program for their patients. After screening, the patients were divided into the ERAS and conventional groups based on the treatment they received. The 2 groups were then compared after the stabilized inverse probability of treatment weighting. The primary end point was the total amount of opioid consumption from surgery to discharge. The secondary end points included daily average and highest pain intensity scores during exertion, opioid-related adverse events, and clinical outcomes, such as length of intensive care unit (ICU) stay, hospital stay, and postoperative complication grade defined by the Clavien-Dindo classification. Additionally, the number of patients discharged without opioids prescription was assessed. RESULTS: Finally, 2120 patients were included in the analysis. The total amount of opioid consumption (median [interquartile range]) after surgery until discharge was lower in the ERAS group (n = 260) than that in the conventional group (n = 1860; morphine milligram equivalents, 44 [16–122] mg vs 208 [146–294] mg; median difference, −143 mg; 95% CI, −154 to −132; P < .001). The number of patients discharged without opioids prescription was higher in the ERAS group (156/260 [60%] vs 329/1860 [18%]; odds ratio, 7.0; 95% CI, 5.3–9.3; P < .001). On operation day, both average pain intensity score during exertion (3.0 ± 1.7 vs 3.5 ± 1.8; mean difference, −0.5; 95% CI, −0.8 to −0.3; P < .001) and the highest pain intensity score during exertion (5.5 ± 2.1 vs 6.4 ± 1.7; mean difference, −0.8; 95% CI, −1.0 to −0.5; P < .001) were lower in the ERAS group than in the conventional group. There were no significant differences in the length of ICU stay, hospital stay, or Clavien-Dindo classification grade. CONCLUSIONS: Patients who underwent pulmonary resection under the ERAS program consumed fewer opioids than those who received conventional management while maintaining no significant differences in clinical outcomes.
Ten-year trends in sex differences in cardiovascular risk factors, in-hospital management, and outcomes of ischemic stroke in China: Analyses of a nationwide serial cross-sectional survey from 2005 to 2015

Background: Women with stroke differ from men in terms of risk factors, treatment, and outcomes. However, previous inconsistent results in China hampered the development of tailored sex-specific strategies for ischemic stroke management. We performed a nationwide serial cross-sectional survey to obtain national-level estimates to assess the 10-year trends in sex differences in cardiovascular risk factors, in-hospital management, and outcomes in China from 2005 to 2015. Methods: We used a two-stage random sampling design, economic-geographical region-stratified random sampling for hospitals first and then systematic sampling for patients, to obtain a nationally representative sample of ischemic strokes in China in 2005, 2010, and 2015. We extracted data on clinical characteristics, management measures (diagnostic tests, interventions, and secondary prevention treatments), in-hospital outcomes (all-cause in-hospital mortality, discharge against medical advice [DAMA], and a composite outcome of in-hospital death and DAMA), and comorbidities. We applied weights proportional to the inverse sampling fraction of hospitals within each stratum and the inverse sampling fraction of patients within each hospital. Results: A total of 26,900 ischemic stroke admissions were analyzed. Compared to men, women had a much lower prevalence of current smokers and a slightly higher prevalence of hypertension, diabetes, dyslipidemia, and atrial fibrillation at admission. Prevalence differences between sex in these cardiovascular risk factors were stable except for atrial fibrillation (decreased from 3.7% [95% CI: 1.8% to 5.7%] to 1.3% [95% CI: 0.5% to 2.0%]) and current smoker (increased from −18.0 [95% CI: –20.2% to –15.9%] to –25.6% [95% CI: –26.6% to –24.6%]). From 2005 to 2015, in-hospital management and outcomes were improved both for women and men, and sex differences in cerebrovascular assessment, cervical vessels assessment, and transthoracic echocardiography/transesophageal echocardiography were improved as well. However, women increased more slowly than men in the administration of clopidogrel (from 0.3% [95% CI: −0.9% to 1.4%) to −7.3% [95% CI: −8.7% to −6.0%]) and aspirin plus clopidogrel (0.3% [95% CI: −5.0% to 1.1%] to −5.0% [95% CI: −6.2% to −3.9%]). Conclusion: Compared to men, women patients with ischemic stroke had a steadily higher prevalence of cardiovascular risk factors, a slower increase rate in the administration of key secondary prevention drugs, and comparable in-hospital outcomes. More effort should be paid to the treatment and control of cardiovascular risk factors and also to the prescription of antiplatelets at discharge for women.
Cingulum bundle integrity in schizophrenia with auditory verbal hallucinations: A diffusion tensor imaging tractographic study

Background & objectives: Cingulum bundle (CB) is frequently implicated in schizophrenia; however, its role in specific symptoms of schizophrenia such as auditory verbal hallucinations (AVHs) is less explored. Few studies have reported association between reduced integrity of CB and severity of AVH. Using a symptom-based approach, this diffusion tensor imaging (DTI) tractographic study was aimed to assess and compare the integrity of CB in schizophrenia with AVH, schizophrenia without AVH and healthy controls. Methods: A total of 92 right-handed adult individuals (aged 18-50 yr) were recruited across three study groups. Those with Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of schizophrenia with AVH (group I; n=30) were compared to those with DSM-5 schizophrenia without lifetime AVH (group II; n=32) and healthy controls (group III; n=30; screened using Mini International Neuropsychiatric Interview version-7.0.0. and negative family history). Clinical assessments (groups I and II) included scale for assessment of positive symptoms, scale for assessment of negative symptoms, clinical global impression-schizophrenia and psychotic symptom rating scale. All participants underwent DTI, and quantitative tract-based measurements of fractional anisotropy (FA) were obtained for images using DTI studio version-3.0. Results: All groups were comparable for age, gender, education and severity of illness. Group I had significantly lower FA values in the cingulate gyrus (CG) part of the left CB compared to groups II and III. No significant difference was found between groups II and III. Interpretation & conclusions: The findings of this study suggest that the disruption in the left CB appears to be specific for AVH-positive schizophrenia. The finding is, however, preliminary subject to replication in future studies. Further investigations are needed to understand its relevance in the context of AVH-positive schizophrenia.
Safety and Efficacy of Liposomal Bupivacaine Supraclavicular Nerve Blocks in Open Treatment of Distal Radius Fractures

Introduction Distal radius fractures (DRFs) are common fractures requiring surgical fixation. The literature varies regarding opioid prescribing habits, opioid consumption, and postoperative pain scores. We hypothesized that the preoperative administration of a liposomal bupivacaine (LB) supraclavicular nerve block would be safe and effective in controlling postoperative pain. Methods A standardized pain management protocol was implemented at a single institution from July 2021 to March 2022 for patients undergoing open reduction internal fixation of DRF. Protocol elements included a preoperative LB supraclavicular nerve block and a multimodal postoperative pain regimen. Primary clinical outcomes included postoperative pain scores and number of opioid tablets consumed. Results Twenty patients underwent a newly implemented protocol. The average age was 56 years. Mean number of oxycodone 5-mg tablets consumed was 4.1 (median, 2.5), and mean visual analog scale pain score at first postoperative appointment was 2.8. There were no incidences of missed acute carpal tunnel postoperatively. When compared with an institutional historical control (n = 189), number of opioid pills prescribed was reduced by 60% (21.4 vs 8.6 tablets, P < 0.0001), and no patients had unscheduled health care contact because of uncontrolled pain (22% vs 0%, P < 0.016). Conclusions Liposomal bupivacaine supraclavicular nerve blocks are safe and effective in the treatment of postoperative pain after open reduction internal fixation of DRF. Patients consumed <5 oxycodone tablets on average, which is less than many recommend prescribed quantities (>20–30 tablets). Patients had low pain scores (2.8/10) at the first postoperative follow-up. To our knowledge, this is the first study demonstrating the utility of LB in this clinical setting.
A mutational hotspot in AMOTL1 defines a new syndrome of orofacial clefting, cardiac anomalies, and tall stature

AMOTL1 encodes angiomotin‐like protein 1, an actin‐binding protein that regulates cell polarity, adhesion, and migration. The role of AMOTL1 in human disease is equivocal. We report a large cohort of individuals harboring heterozygous AMOTL1 variants and define a core phenotype of orofacial clefting, congenital heart disease, tall stature, auricular anomalies, and gastrointestinal manifestations in individuals with variants in AMOTL1 affecting amino acids 157–161, a functionally undefined but highly conserved region. Three individuals with AMOTL1 variants outside this region are also described who had variable presentations with orofacial clefting and multi‐organ disease. Our case cohort suggests that heterozygous missense variants in AMOTL1, most commonly affecting amino acid residues 157–161, define a new orofacial clefting syndrome, and indicates an important functional role for this undefined region.
EVALUATION OF PM10 EMISSION FROM FARROWING AND FATTENING SWINE ROOMS BY CONTINUOUS ON-LINE MEASUREMENTS

In this study, PM10 emission factors were studied in both the farrowing and fattening rooms of a piggery. The following climatic and managerial variables were monitored online, in both rooms, throughout the observation period; temperature and humidity (internal and external), ventilation rate, heating, number and weight of animals and type of feed administration. PM10 concentration was also measured continuously in both rooms, and also at the inlet level of the fattening room, to estimate dust coming from the external environment, using a Haz Dust EPAM 5000 (EDC) sampler which is based on the near-forward light scattering method. The emission factor of particulate matter (PM10) was calculated by taking into account PM10 concentrations both inside and outside the building, and the ventilation rate (air volumes extracted from the stable). Correlations between PM10 concentration and the considered variables were studied. The PM10 emission was estimated at 6.8 mg head-1 h-1 from the farrowing room, and at 12.03 mg head-1 h-1 from the fattening room.
Developing an alliance scan for measurement of exploratory inter-firm relationships

Inter-firm relationship management has been proven to be important in the attainment of competitive advantages by looking at various aspects of relationship management (Linnarsson & Werr, 2005). However, for exploratory partnerships, the number of elements are high and interlinks are complex. This paper uses a literature review method for investigating the topic of dyadic inter-firm relations to draw insights into the relationship management categories and their respective elements. Based on relational, structural, resource and strategic dimensions, an alliance scan tool was developed to differentiate these relationship attributes and to provide key stakeholders an efficient tool for partnership decision making. This tool can be used as a starting point for future research regarding the typologies and actionable research based decisions.
Structural Mechanisms of NLRP3 Inflammasome Assembly and Activation.

As an important sensor in the innate immune system, NLRP3 detects exogenous pathogenic invasions and endogenous cellular damage and responds by forming the NLRP3 inflammasome, a supramolecular complex that activates caspase-1. The three major components of the NLRP3 inflammasome are NLRP3, which captures the danger signals and recruits downstream molecules; caspase-1, which elicits maturation of the cytokines IL-1β and IL-18 and processing of gasdermin D to mediate cytokine release and pyroptosis; and ASC (apoptosis-associated speck-like protein containing a caspase recruitment domain), which functions as a bridge connecting NLRP3 and caspase-1. In this article, we review the structural information that has been obtained on the NLRP3 inflammasome and its components or subcomplexes, with special focus on the inactive NLRP3 cage, NEK7 (NIMA-related kinase 7)-licensing of NLRP3 activation, and the PYD-PYD and CARD-CARD homotypic filamentous scaffolds of the inflammasome. We further implicate structure-derived mechanisms for the assembly and activation of the NLRP3 inflammasome. Expected final online publication date for the Annual Review of Immunology, Volume 41 is April 2023. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.