Miracle-dz/UniFAR-FTUs huggingface dataset:
The Impact of Social Determinants of Health in Facial and Craniomaxillofacial Reconstruction: Can We Do Better?

Social determinants of health (SDOH) are integral to consider when delivering craniomaxillofacial and facial reconstructive care for patients. The American Cleft Palate-Craniofacial Association (ACPA) has instituted a formalized multidisciplinary care team model that recognizes such determinants and has aggregated patient-led organizations to strengthen patients’ education and support system. This review discusses the need for all surgeons engaged in facial and craniomaxillofacial reconstruction to consider SDOH in their practice. Additionally, we explore how factors such as race, insurance status, education level, cost, and access to follow-up care, impact surgical care for craniosynostosis, facial trauma, orthognathic surgery, head and neck cancer, and facial paralysis. We propose that the ACPA team model be applied to other societies that care for the broader scope of patients in need of facial and craniomaxillofacial reconstruction to strengthen the communication, collaboration, and standardization of care delivery that is personalized to the needs of each patient.
A clubroot pathogen effector targets cruciferous cysteine proteases to suppress plant immunity

ABSTRACT Plant pathogen effector proteins are key to pathogen virulence. In susceptible host Brassicas, the clubroot pathogen, Plasmodiophora brassicae, induces the production of nutrient-sink root galls, at the site of infection. Among a list of 32 P. brassiae effector candidates previously reported by our group, we identified SSPbP53 as a putative apoplastic cystatin-like protein highly expressed during the secondary infection. Here we found that SSPbP53 encoding gene is conserved among several P. brassicae pathotypes and that SSPbP53 is an apoplastic protein able to directly interact with and inhibit cruciferous papain-like cysteine proteases (PLCPs), specifically Arabidopsis XYLEM CYSTEINE PEPTIDASE 1 (AtXCP1). The severity of clubroot disease is greatly reduced in the Arabidopsis xcp1 null mutant (AtΔxcp1) after infection with P. brassicae resting spores, indicating that the interaction of P. brassicae SSPbP53 with XCP1 is important to clubroot susceptibility. SSPbP53 is the first cystatin-like effector identified and characterized for a plant pathogenic protist.
The effects of a clinic‐based weight loss program on health‐related quality of life and weight maintenance in cancer survivors: A randomized controlled trial

The Healthy Living and Eating After Cancer Trial demonstrated that a clinic‐based weight loss program reduced body weight, as compared with a waitlist control group, over 15 weeks. Here we report the impact of the weight loss intervention on health‐related quality‐of‐life outcomes at week 15, and maintenance of weight loss to week 30.
Impervious to Randomness: Confounding and Selection Biases in Randomized Clinical Trials

Abstract The random allocation of therapies in randomized clinical trials is a powerful tool that removes all confounding biases that can affect treatment assignment. However, confounders influencing mediators of the treatment effect are unaffected by randomization and should be considered during trial design and statistical modeling. Examples of such mediators include biomarkers predictive of response to targeted therapies in oncology. Patient selection for such biomarkers is prudent in clinical trials. Conversely, prognostic information on outcome heterogeneity can be derived from observational datasets that include more representative populations. The fusion of experimental and observational data can then allow patient-specific inferences.
Cluster analysis identifies unmet healthcare needs among patients with rheumatoid arthritis

Objective To identify the patterns of healthcare resource utilization and unmet needs of persistent disease activity, pain, and physical disability in rheumatoid arthritis (RA) by cluster analysis. Method Patients attending the Jyväskylä Central Hospital rheumatology unit, Finland, were, from 2007, prospectively enrolled in a clinical database. We identified all RA patients in 2010–2014 and combined their individual-level data with well-recorded administrative data on all public healthcare contacts in fiscal year 2014. We ran agglomerative hierarchical clustering (Ward’s method), with 28-joint Disease Activity Score with three variables, Health Assessment Questionnaire index, pain (visual analogue scale 0–100), and total annual health service-related direct costs (€) as clustering variables. Results Complete-case analysis of 939 patients derived four clusters. Cluster C1 (remission and low costs, 550 patients) comprised relatively young patients with low costs, low disease activity, and minimal disability. C2 (chronic pain, disability, and fatigue, 269 patients) included those with the highest pain and fatigue levels, and disability was fairly common. C3 (inflammation, 97 patients) had rather high mean costs and the highest average disease activity, but lower average levels of pain and less disability than C2, highlighting the impact of effective treatment. C4 (comorbidities and high costs, 23 patients) was characterized by exceptionally high costs incurred by comorbidities. Conclusions The majority of RA patients had favourable outcomes and low costs. However, a large group of patients was distinguished by chronic pain, disability, and fatigue not unambiguously linked to disease activity. The highest healthcare costs were linked to high disease activity or comorbidities.
Combination immunotherapy of chlorogenic acid liposomes modified with sialic acid and PD-1 blockers effectively enhances the anti-tumor immune response and therapeutic effects

Abstract Melanoma is one of the most common malignant tumors. The anti-PD-1 antibody is used for the treatment of metastatic melanoma. Treatment success is only 35–40% and a range of immune-related adverse reactions can occur. Combination of anti-PD1 antibody therapy with other oncology therapies has been attempted. Herein, we assessed whether chlorogenic acid liposomes modified with sialic acid (CA-SAL) combined with anti-PD1 antibody treatment was efficacious as immunotherapy for melanoma. CA-SAL liposomes were prepared and characterized. In a mouse model of B16F10 tumor, mice were treated with an anti-PD1 antibody, CA-SAL, or combination of CA-SAL + anti-PD1 antibody, and compared with no treatment controls. The tumor inhibition rate, tumor-associated macrophages (TAMs) phenotype, T-cell activity, and safety were investigated. We observed a significant decrease in the proportion of M2-TAMs and CD4+Fop3+ T cells, while there was a significant increase in the proportion of M1-TAMs and CD8+ T cells, and in the activity of T cells, and thus in the tumor inhibition rate. No significant toxicity was observed in major organs. CA-SAL and anti-PD1 Ab combination therapy presented synergistic anti-tumor activity, which enhanced the efficacy of the PD-1 checkpoint blocker in a mouse model of melanoma. In summary, combination immunotherapy of CA-SAL and anti-PD1 Ab has broad prospects in improving the therapeutic effect of melanoma, and may provide a new strategy for clinical treatment.
Impact of assistance on peritonitis due to breach in aseptic procedure in diabetic patients: A cohort study with the RDPLF data

Background: Diabetic patients often have physical impairment that could lead to manipulation errors in peritoneal dialysis (PD) and touch contamination. Nurse assistance in diabetic PD patients is known to help prevent peritonitis. We made the hypothesis that this lower risk of peritonitis was observed thanks to prevention of breach in aseptic procedure. We evaluated the impact of nurse-assisted PD on specific causes of peritonitis, especially on peritonitis due to a breach in aseptic procedure. Methods: This was a retrospective observational study of the data from the French Language Peritoneal Dialysis Registry. All diabetic patients older than age 18 years starting PD in France between 1 January 2012 and 31 December 2015 were included in the study. The event of interest was the first peritonitis event due to a breach in aseptic procedure. Death, kidney transplantation and peritonitis due to another mechanism were considered as competing events. We examined the association of the covariates with all the possible outcomes using a subdistribution hazard model developed for survival analysis in the presence of competing risks. Results: Four thousand one hundred one diabetic patients incident in PD were included in the study. At least one peritonitis event occurred in 1611 patients over the study period. A breach in aseptic procedure was reported in 441/1611 cases (27.3%): 209/575 (36.3%) in the self-care PD group, 56/217 (25.8%) in the family-assisted PD group and 176/819 (21.5%) in the nurse-assisted PD group. Both nurse and family assistance were associated with a lower risk of peritonitis due to breach in aseptic procedure in bivariate analysis. After adjustment on age, modified Charlson index, sex and diabetic nephropathy, patients treated by nurse-assisted PD (subdistribution hazard ratio (sd-HR) 0.52, 95% confidence interval (CI) 0.40–0.67) and those treated by family-assisted PD (sd-HR 0.70, 95% CI 0.51–0.95) had a lower likelihood of peritonitis due to a connection error compared to self-care PD in multivariate analysis. The modality of assistance was not associated with other causes of peritonitis in the multivariate analysis. Conclusion: While both nurse-assisted PD and family-assisted PD were associated with lower risk of peritonitis due to a breach in aseptic procedure compared to self-care PD in our study, the protective effect was greater with nurse assistance.
Hippocampal and striatal volumes correlate with spatial memory impairment in Huntington’s disease

Spatial memory impairments are observed in people with Huntington's disease (HD), however, the domain of spatial memory has received little focus when characterizing the cognitive phenotype of HD. Spatial memory is traditionally thought to be a hippocampal‐dependent function, while the neuropathology of HD centers on the striatum. Alongside spatial memory deficits in HD, recent neurocognitive theories suggest that a larger brain network is involved, including the striatum. We examined the relationship between hippocampal and striatal volumes and spatial memory in 36 HD gene expansion carriers, including premanifest (n = 24) and early manifest HD (n = 12), and 32 matched healthy controls. We assessed spatial memory with Paired Associates Learning, Rey–Osterrieth Complex Figure Test, and the Virtual House task, which assesses three components of spatial memory: navigation, object location, and plan drawing. Caudate nucleus, putamen, and hippocampal volumes were manually segmented on T1‐weighted MR images. As expected, caudate nucleus and putamen volumes were significantly smaller in the HD group compared to controls, with manifest HD having more severe atrophy than the premanifest HD group. Hippocampal volumes did not differ significantly between HD and control groups. Nonetheless, on average, the HD group performed significantly worse than controls across all spatial memory tasks. The spatial memory components of object location and recall of figural and topographical drawings were associated with striatal and hippocampal volumes in the HD cohort. We provide a case to include spatial memory impairments in the cognitive phenotype of HD, and extend the neurocognitive picture of HD beyond its primary pathology within the striatum.
Method development for mono‐ and disaccharides monitoring in cell culture medium by capillary and microchip electrophoresis

The rapidly growing, competitive biopharmaceutical market requires tight bioprocess monitoring. An integrated, automated platform for the routine online/at‐line monitoring of key factors in the cell culture medium could greatly improve process monitoring. Mono‐ and disaccharides, as the main energy and carbon source, are one of these key factors. A CE‐LIF method was developed for the analysis of several mono‐ and disaccharides, considering requirements and restrictions for analysis in an integrated, automated monitoring platform, such as the possibility for miniaturization to microchip electrophoresis. Analysis was performed after fluorescent derivatization with 8‐aminopyrene‐1,3,6‐trisulfonic acid. The derivatisation reaction and the separation BGE were optimized using design of experiments. The developed method is applicable to the complex matrix of cell culture medium and proved transferable to microchip electrophoresis.
Biological and clinical implications of metastasis‐associated circular RNAs in oesophageal squamous cell carcinoma

Oesophageal squamous cell carcinoma (OSCC) is a prevalent malignancy with high morbidity and mortality as a result of early metastasis and poor prognosis. Metastasis is a multistep process, involving various signalling pathways. Circular RNAs (circRNAs) are a class of covalently closed noncoding RNAs, the aberrant expression of which is reported to be involved in several biological events, including cell transformation, proliferation, migration, invasion, apoptosis and metastasis. Several studies have reported interactions between circRNAs and metastasis‐associated signalling pathways. The abundance, stability and highly specific expression of candidate circRNAs make them potential biomarkers and therapeutic targets in OSCC. In this review article, we comprehensively describe metastasis‐related circRNAs and their interactions with epithelial–mesenchymal transition‐associated molecules. We also describe the molecular mechanisms and clinical relevance of circRNAs in OSCC progression and metastasis.
Black raspberry (Rubus occidentalis) attenuates inflammatory markers and vascular endothelial dysfunction in Wistar rats fed a high-fat diet with fructose solution.

A continuous high-fat/high-fructose diet induces inflammation and lowers vascular endothelial function in the body. This research examined the effects of black raspberry (BR) powder consumption on the inflammatory response and endothelial dysfunction in rats fed with a high-fat diet and fructose solution. Wistar rats were randomly divided into two groups as control (AIN-93G diet + distilled water) and HFF (high-fat diet + 20% fructose solution) groups, for 16 weeks. At 8 weeks, the HFF was further divided into three subgroups: HFF, HFFBR2.5 (2.5% BR in high-fat diet), and HFFBR5 (5% BR in high-fat diet). The BR-fed groups showed significantly higher high-density lipoprotein-cholesterol and lower triglycerides than the HFF group. Rats supplemented with BR showed decreased mRNA and protein expressions of inflammatory cytokines and adhesion molecules in the liver and aorta tissues. Furthermore, the aortic protein expression of endothelial nitroxide synthase was significantly greater in the HFFBR2.5 and HFFBR5 than HFF. PRACTICAL APPLICATIONS: Black raspberry (BR: Rubus occidentalis) is abundant in flavonoids and anthocyanins. BR displays various biological activities and has been used to alleviate inflammatory conditions. In our study, BR supplementation showed promising effects against high-fat/high-fructose diet-induced inflammation and endothelial dysfunction in rats by decreasing markers of inflammation and improving vascular endothelial function. These findings suggest that BR consumption could have beneficial effects on the risk factors of cardiovascular disease.
Dopamine biases sensitivity to personal goals and social influence in self-control over everyday desires

People regularly give in to daily temptations in spite of conflict with personal goals. To test hypotheses about neuropharmacological influences on self-control, we used positron emission tomography to measure dopamine D2-like receptors (D2R) and experience sampling surveys to naturalistically track daily desires outside the laboratory in everyday life in a sample of 103 adults. Higher D2R availability in the ventral striatum was associated with increased sensitivity to personal goal conflict but not desire strength in deciding whether to attempt to resist a desire. The influence of D2Rs on sensitivity to personal goal conflict depended on whether desires were experienced in a social context. D2R availability in the midbrain (but not the ventral striatum) influenced whether desires were enacted. These findings provide unique evidence that the dopamine system influences decision making and regulatory behavior and provides new insights into how these mechanisms interact with personal goals and social contexts.
Erectile dysfunction resulting from pelvic surgery is associated with changes in cavernosal gene expression indicative of cavernous nerve injury

Pelvic surgery, even without direct cavernous nerve injury, carries a high risk of post‐operative erectile dysfunction. The present studies were aimed at identifying molecular mechanisms by which pelvic surgery results in erectile dysfunction. As a model of pelvic surgery, male Sprague–Dawley rats underwent pelvic laparotomy, avoiding direct cavernous nerve injury. A second group of animals, serving as a model of direct cavernous nerve injury, underwent bilateral transection of the cavernous nerve. Cavernosometry demonstrated, that even in the absence of direct nerve injury, the pelvic surgery model exhibited significant erectile dysfunction 3 days post‐operatively. Gene expression profiling also demonstrated that even in this animal model of nerve‐sparing pelvic surgery, the profile of differentially expressed genes in cavernosal tissue was indicative of cavernous nerve injury. In addition, although 6 hr after surgery there were significant changes in circulating cytokine/chemokine levels, an inflammatory response in the major pelvic ganglion, cavernous nerve and cavernosal tissue was only observed 3 days post‐surgery. Our results validate a rat model of pelvic surgery exhibiting erectile dysfunction and suggest systemic release of cytokines/chemokines following surgical trauma might mediate a pathological inflammatory response in tissues distal to the site of surgical trauma, indirectly resulting in cavernous nerve injury and erectile dysfunction.
Essential functions of mosquito ecdysone importers in development and reproduction

The primary insect steroid hormone ecdysone requires a membrane transporter to enter its target cells. Although an organic anion-transporting polypeptide (OATP) named Ecdysone Importer (EcI) serves this role in the fruit fly Drosophila melanogaster and most likely in other arthropod species, this highly conserved transporter is apparently missing in mosquitoes. Here we report three additional OATPs that facilitate cellular incorporation of ecdysone in Drosophila and the yellow fever mosquito Aedes aegypti. These additional ecdysone importers (EcI-2, 3, and 4) are dispensable for development and reproduction in Drosophila, consistent with the predominant role of EcI. In contrast, in Aedes, EcI-2 is indispensable for ecdysone-mediated development, whereas EcI-4 is critical for vitellogenesis induced by ecdysone in adult females. Altogether, our results indicate unique and essential functions of these additional ecdysone importers in mosquito development and reproduction, making them attractive molecular targets for species- and stage-specific control of ecdysone signaling in mosquitoes.
Transmembrane region dimer structures of Type 1 receptors readily sample alternate configurations: MD simulations using the Martini 3 coarse grained model compared to AlphaFold2 Multimer

Determination of the structure and dynamics of transmembrane (TM) regions of single-transmembrane receptors is key to understanding their mechanism of signal transduction across the plasma membrane. Although many studies have been performed on isolated soluble extra- and intracellular receptor domains in aqueous solutions, limited knowledge exists on the lipid embedded TM domain. In this study, we examine the assembly of configurations of receptor TM region dimers using the Martini 3 force field for coarse-grain (CG) molecular dynamics simulations. This recently published version of Martini has new bead types and sizes, which allows more accurate predictions of molecular interactions compared to the previous versions. At first glance our results with Martini 3 simulations show only a reasonable agreement with ab initio predictions using PREDDIMER (for TM domains only), AlphaFold2 Multimer and with available NMR derived structures for TM helix dimers. Specifically, 6 of 11 CG TM structures are similar to the NMR structures (within < 3.5 Å mainchain RMSD) compared to 10 of 11 and 9 of 11 using PREDDIMER and Alphafold, respectively (7 structures of the latter are within 1.5 Å) Surprisingly, AlphaFold2 predictions are more comparable with NMR structures when the database of 2001 (mainly composed of soluble proteins) instead of 2020 PDB structures are used. While there are some differences in the conditions used, the CG simulations primarily reveal that alternate configurations of the TM dimers that are sampled, which readily interconvert with a predominant population. The implications of these findings for our understanding of the signalling mechanism of TM receptors are discussed, including opportunities for the development of new pharmaceuticals, some of which are peptide based.
Phomoarcherin B as a novel HIV-1 reverse transcriptase RNase H activity inhibitor: conclusions from comprehensive computational analysis

The HIV epidemic has claimed more than 32.7 million live since its emergence in 1981, while many ART and HAART therapies are available and provide relief and control for patients, most of these therapeutics come with long-term side effects, resistance, socio-economical barriers, and other obstacles. In this study, genomic analysis was performed on 98 HIV-1 genomes to determine the most coherent target that could be utilized to restrict and cease the viral replication, the reverse transcriptase enzyme. Following the identification of the target protein, the RNase H activity of the reverse transcriptase was nominated as the potent target given the limited research associated with it. A library of 94 thousand small molecule inhibitors was generated and virtual screening was performed to identify hits, based on the reproducibility of the screening results, 4 compounds with the best scores were considered and their interaction within the active site was analyzed. Subsequently, all-atom molecular dynamics simulations and MM-PBSA was performed to validate the stability and binding free energy of the hits within the RNase H active. In silico ADMET assays were performed on the hit compounds to analyze their drug-likeness, physicochemical and pharmacological properties. Phomoarcherin B, a pentacyclic aromatic sesquiterpene naturally found in the endophytic fungus Phomopsis archeri, known for its anticancer properties scored the best in all the experiments and was nominated as a potential inhibitor of the HIV-1 reverse transcriptase RNase H activity. Author Summary The Human immunodeficiency virus 1 (HIV-1) has remained a global public health issue for the past 4 decades with millions of patients around the globe affected. Long years of research in the field of anti-viral therapies had introduced several drugs to combat the viral infection, however, most of these drugs come with their shortcomings. In this study, computational drug discovery approaches were utilized to research novel drugs that could be used as anti-viral agents against the former virus, the results had revealed Phomoarcherin B, a natural compound from an endophytic fungus to hold promising therapeutic potentials.