Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical Significance of TP53 Abnormalities in Newly Diagnosed Multiple Myeloma

Objective: This study aimed to identify the clinical significance of TP53 and common cytogenetic abnormalities. Materials and Methods: A total of 114 patients with newly diagnosed multiple myeloma (MM) and TP53 abnormalities were selected from two large patient cohorts of collaborating hospitals from 2010 to 2017. The characteristics and outcomes of these patients were analyzed. TP53 and other common mutations in MM patients were quantified by fluorescence in situ hybridization. Kaplan-Meier curves and log-rank tests were applied for survival analysis. A Cox proportional hazard model for covariate analysis was used to determine the prognostic factors. Results: By extensive data analysis, we found that TP53 amplification is a strong positive predictor for complete response (CR) to therapy and positively correlated with patient survival. The number of simultaneous genomic abnormalities with TP53 mutation has a modest impact on patient survival. Among these mutations, 1q21 amplification is associated with decreased CR (odds ratio: 4.209) and FGFR3 levels are positively correlated with progression-free and overall survival. Conclusion: TP53 abnormalities at the diagnosis of MM are of great clinical significance in predicting patient response to therapy and survival. Furthermore, 1q21 and FGFR3 mutations could potentially be used in combination with TP53 status to better predict patient survival and guide the selection of high-risk patients to advance patient treatment strategies.
The acceptability and feasibility of screening, brief intervention, and referral to treatment for pain management among new England veterans with chronic pain: A pilot study

Musculoskeletal disorders often lead to chronic pain in Veterans. Chronic pain puts sufferers at risk for substance misuse, and early intervention is needed for both conditions. This pilot study tested the feasibility and acceptability of a Screening, Brief Intervention, and Referral to Treatment for Pain Management intervention (SBIRT‐PM) to help engage Veterans seeking disability compensation for painful musculoskeletal disorders in multimodal pain treatment and to reduce risky substance use, when indicated.
Interannual variation in rainfall modulates temperature sensitivity of carbon allocation and flux in a tropical montane wet forest

Tropical forests exert a disproportionately large influence on terrestrial carbon (C) balance but projecting the effects of climate change on C cycling in tropical forests remains uncertain. Reducing this uncertainty requires improved quantification of the independent and interactive effects of variable and changing temperature and precipitation regimes on C inputs to, cycling within and loss from tropical forests. Here, we quantified aboveground litterfall and soil‐surface CO2 efflux (“soil respiration”; FS) in nine plots organized across a highly constrained 5.2°C mean annual temperature (MAT) gradient in tropical montane wet forest. We used five consecutive years of these measurements, during which annual rainfall (AR) steadily increased, in order to: (a) estimate total belowground C flux (TBCF); (b) examine how interannual variation in AR alters the apparent temperature dependency (Q10) of above‐ and belowground C fluxes; and (c) quantify stand‐level C allocation responses to MAT and AR. Averaged across all years, FS, litterfall, and TBCF increased positively and linearly with MAT, which accounted for 49, 47, and 46% of flux rate variation, respectively. Rising AR lowered TBCF and FS, but increased litterfall, with patterns representing interacting responses to declining light. The Q10 of FS, litterfall, and TBCF all decreased with increasing AR, with peak sensitivity to MAT in the driest year and lowest sensitivity in the wettest. These findings support the conclusion that for this tropical montane wet forest, variations in light, water, and nutrient availability interact to strongly influence productivity (litterfall+TBCF), the sensitivity of above‐ and belowground C fluxes to rising MAT (Q10 of FS, litterfall, and TBCF), and C allocation patterns (TBCF:[litterfall+TBCF]).
Embryonic ethanol exposure on zebrafish early development

Embryonic exposure to ethanol leads to a condition of physical, behavioral, and cognitive deficiencies named fetal alcohol spectrum disorders (FASD). The most severe variations are in fetal alcohol syndrome (FAS), which is easier to diagnose and not studied in animal models. On the other side, the pFAS (partial fetal alcohol syndrome) includes cases of alcohol‐related congenital disabilities and neurodevelopmental disorder with an inconclusive diagnosis. In recent years, the zebrafish has become a valuable model to study FASD and its variations.
Cultural Perspectives on Pain Assessment and Opioid Use: International Neuroscience Nursing Research Symposium Conference Proceedings

ABSTRACT INTRODUCTION: In August of 2020, the 4th International Neuroscience Nursing Research Symposium was held. The purpose of the symposium was to share neuroscience nursing research from around the world. One of the topics thought most notable that stimulated a crucial conversation was how different countries assessed pain and their use of opioids for pain management. BACKGROUND: Neuroscience nurses are global. What is not known is their experience with and what challenges exist with pain management for human beings in their country. Crossing geographic and cultural boundaries, pain affects all human beings. Each culture has unique values and beliefs regarding pain. Patient barriers, pivotal in this article, included poverty, poor health literacy, opioid phobia, and cultural as well as social beliefs. RESULTS: Neuroscience nurses from Australia, Brazil, Germany, Singapore, India, Ghana, Kenya, Philippines, South Africa, and the United States each collaborated to provide a short summary of assessing pain and use of opioids for pain management for the neuroscience patient. CONCLUSION: Neuroscience patients have varying degrees of pain based on many factors. Various countries have religious, spiritual, and cultural traditions that influence the reporting and management of pain. Pain assessment and management can be challenging, especially for the neuroscience nurses around the world.
Analysis of three-dimensional imaging findings and clinical symptoms in patients with temporomandibular joint disorders.

Background The purpose of this study was to analyze cone-beam computed tomography (CBCT) and magnetic resonance imaging (MRI) findings in temporomandibular joint disorder (TMD) patients and to comprehensively assess the relationships between these imaging findings and clinical symptoms. Methods A total of 754 temporomandibular joints (TMJs) in 377 patients with clinical symptoms of TMD who underwent both CBCT and MRI examinations were retrospectively reviewed. Clinical symptoms included TMJ pain, TMJ sound, and limitation of mouth opening. Oral radiologists evaluated osseous changes of the condylar head on CBCT, as well as the disc configuration, internal derangement, and joint effusion on MRI. The frequency of CBCT and MRI findings and the mean and standard deviation of age were analyzed. Logistic regression analysis was used to identify associations between these imaging findings and clinical symptoms using SPSS version 25.0 for Windows (IBM Corp., Armonk, NY, USA). The model fit was evaluated using the Hosmer and Lemeshow test. Results TMD patients consisted of 294 females and 83 males, and the age group of 20-39 accounted for 47.2% of the patients. Normal findings regarding osseous changes of the condylar head on CBCT were found in 65.1% of the patients. On MRI, a change in disc configuration was found in 54.9% of the patients, internal derangement in 62.6%, and joint effusion in 46.0%. TMJ pain was significantly associated with sclerosis [odds ratio (OR): 3.81], disc displacement without reduction (DDWOR) (OR: 3.22), grade 2 joint effusion (OR: 2.33), and grade 3 joint effusion (OR: 5.54). TMJ sound was significantly associated with disc displacement with reduction (DDWR) (OR: 3.04), DDWOR (OR: 2.50), grade 2 joint effusion (OR: 2.37), and grade 3 joint effusion (OR: 3.23). Limitation of mouth opening was significantly associated with flattened disc configuration (OR: 2.08), folded disc configuration (OR: 2.30), and grade 3 joint effusion (OR: 2.85). Conclusions CBCT findings had little to do with clinical symptoms. In contrast, MRI findings, including disc configuration, internal derangement, and joint effusion, were associated with clinical symptoms. These results suggest that MRI should be recommended over CBCT for the proper diagnosis of TMD patients.
Infant gut microbiota modulation by human milk disaccharides in humanized microbiome mice

ABSTRACT Human milk glycans present a unique diversity of structures that suggest different mechanisms by which they may affect the infant microbiome development. A humanized mouse model generated by infant fecal transplantation was utilized here to evaluate the impact of fucosyl-α1,3-GlcNAc (3FN), fucosyl-α1,6-GlcNAc, lacto-N-biose (LNB) and galacto-N-biose on the fecal microbiota and host–microbiota interactions. 16S rRNA amplicon sequencing showed that certain bacterial genera significantly increased (Ruminococcus and Oscillospira) or decreased (Eubacterium and Clostridium) in all disaccharide-supplemented groups. Interestingly, cluster analysis differentiates the consumption of fucosyl-oligosaccharides from galactosyl-oligosaccharides, highlighting the disappearance of Akkermansia genus in both fucosyl-oligosaccharides. An increment of the relative abundance of Coprococcus genus was only observed with 3FN. As well, LNB significantly increased the relative abundance of Bifidobacterium, whereas the absolute levels of this genus, as measured by quantitative real-time PCR, did not significantly increase. OTUs corresponding to the species Bifidobacterium longum, Bifidobacterium adolescentis and Ruminococcus gnavus were not present in the control after the 3-week intervention, but were shared among the donor and specific disaccharide groups, indicating that their survival is dependent on disaccharide supplementation. The 3FN-feeding group showed increased levels of butyrate and acetate in the colon, and decreased levels of serum HDL-cholesterol. 3FN also down-regulated the pro-inflammatory cytokine TNF-α and up-regulated the anti-inflammatory cytokines IL-10 and IL-13, and the Toll-like receptor 2 in the large intestine tissue. The present study revealed that the four disaccharides show efficacy in producing beneficial compositional shifts of the gut microbiota and in addition, the 3FN demonstrated physiological and immunomodulatory roles.
LINE‐1 vectors mediate recombinant antibody gene transfer by retrotransposition in Chinese hamster ovary cells

Retrotransposons, such as long interspersed element‐1 (LINE‐1), can copy themselves to other genomic loci via a transposition event (termed retrotransposition). Retrotransposons, therefore, have potential use as an efficient gene delivery tool to integrate multiple copies of a target gene into a host genome. Here, we developed a retrotransposon vector based on LINE‐1 that achieves target gene integration of multiple transgene copies.
Enteric mesenchymal cells support the growth of postnatal enteric neural stem cells

Interplay between embryonic enteric neural stem cells (ENSCs) and enteric mesenchymal cells (EMCs) in the embryonic gut is essential for normal development of the enteric nervous system. Disruption of these interactions underlies the pathogenesis of intestinal aganglionosis in Hirschsprung disease (HSCR). ENSC therapy has been proposed as a possible treatment for HSCR, but whether the survival and development of postnatal‐derived ENSCs similarly rely on signals from the mesenchymal environment is unknown and has important implications for developing protocols to expand ENSCs for cell transplantation therapy. Enteric neural crest‐derived cells (ENCDCs) and EMCs were cultured from the small intestine of Wnt1‐Rosa26‐tdTomato mice. EMCs promoted the expansion of ENCDCs 9.5‐fold by inducing ENSC properties, including expression of Nes, Sox10, Sox2, and Ngfr. EMCs enhanced the neurosphere‐forming ability of ENCDCs, and this persisted after withdrawal of the EMCs. These effects were mediated by paracrine factors and several ligands known to support neural stem cells were identified in EMCs. Using the optimized expansion procedures, neurospheres were generated from small intestine of the Ednrb−/− mouse model of HSCR. These ENSCs had similar proliferative and migratory capacity to Ednrb+/+ ENSCs, albeit neurospheres contained fewer neurons. ENSCs derived from Ednrb−/− mice generated functional neurons with similar calcium responses to Ednrb+/+ ENSCs and survived after transplantation into the aganglionic colon of Ednrb−/− recipients. EMCs act as supporting cells to ENSCs postnatally via an array of synergistically acting paracrine signaling factors. These properties can be leveraged to expand autologous ENSCs from patients with HSCR mutations for therapeutic application.
Neuromuscular blockade management in patients with COVID-19

This narrative review evaluates the evidence for using neuromuscular blocking agents (NMBA) in patients being treated for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While large prospective randomized-controlled trials (RCTs) are lacking at this point in time, smaller observational studies and case series are reviewed to ascertain the indications and utility of NMBAs. Additionally, large RCTs that address similar clinical scenarios are reviewed and the authors translate these findings to patients with COVID-19. Specifically, NMBAs can be helpful during endotracheal intubation to minimize the risk of patient coughing and possibly infecting healthcare personnel. NMBAs can also be used in patients to promote patient-ventilator synchrony while reducing the driving pressure needed with mechanical ventilation (MV), particularly in patients with the severe clinical presentation (Type H phenotype). Prone positioning has also become a cornerstone in managing refractory hypoxemia in patients with SARS-CoV-2 acute respiratory distress syndrome, and NMBAs can be useful in facilitating this maneuver. In the perioperative setting, deep levels of neuromuscular blockade can improve patient outcomes during laparoscopic operations and may theoretically reduce the risk of aerosolization as lower insufflation pressures may be utilized. Regardless of the indication, quantitative neuromuscular monitoring remains the only reliable method to confirm adequate recovery following cessation of neuromuscular blockade. Such monitors may serve a unique purpose in patients with COVID-19 as automation of measurements can reduce healthcare personnel-patient contact that would occur during periodic subjective evaluation with a peripheral nerve stimulator.
Extracorporeal Cytokine Adsorption Therapy As a Preventive Measure in Cardiac Surgery and As a Therapeutic Add-On Treatment in Sepsis: An Updated Systematic Review of Comparative Efficacy and Safety*

Supplemental Digital Content is available in the text. OBJECTIVES: Evaluating whether there is a clinical benefit of using extracorporeal cytokine adsorption therapy in two indications. DESIGN: Systematic review. SETTING: Search on four databases, Medline, Embase, The Cochrane Library, and the European Network for Health Technology Assessment planned and ongoing projects database. PATIENTS: Patients with sepsis/septic shock; patients undergoing cardiac surgery INTERVENTIONS: Cytokine adsorption. MEASUREMENTS AND MAIN RESULTS: Randomized controlled trials and prospective studies with concurrent control were eligible for the evidence synthesis. The quality of the individual studies and the strength of the available evidence were assessed using the Cochrane risk of bias tool and the Grading of Recommendations, Assessment, Development, and Evaluation approach, respectively. For the preventive treatment of extracorporeal cytokine adsorption therapy in patients undergoing cardiac surgery, we found very low-quality inconclusive evidence for mortality (five randomized controlled trials, n = 163), length of stay in the ICU (five randomized controlled trials, n = 163), and length of hospitalization (three randomized controlled trials, n = 101). Very low-quality inconclusive evidence was found for (serious) adverse events (four randomized controlled trials, n = 148). For the therapeutic treatment of extracorporeal cytokine adsorption therapy in patients with sepsis/septic shock, we found very low-quality inconclusive evidence for mortality up to 60-day follow-up (two randomized controlled trials, n = 117), organ function (two randomized controlled trials, n = 117) and length of stay in the ICU (one randomized controlled trial, n = 20). Very low-quality inconclusive evidence was found for (serious) adverse events (two randomized controlled trials, n = 117). CONCLUSIONS: Given the available evidence, the efficacy and safety of extracorporeal cytokine adsorption therapy in combination with standard care in the investigated indications was not established. We strongly recommend considering well-powered studies with patient-relevant endpoints instead of investing further research funds on studies that may not shed light on the clinical benefit of extracorporeal cytokine adsorption therapy.
A French cohort of patients with giant cell arteritis: glucocorticoid treatment and its associated side effects.

OBJECTIVES Giant cell arteritis (GCA) is the most common primary large-vessel vasculitis. Glucocorticoids (GC) therapy remains the standard of care for GCA despite frequent side effects (SEs). However, treatment modality changes, prophylactic treatment of osteoporosis, or vaccinations might have decreased the frequency of GC-related SEs. This study aims to describe GCA treatment and GC-related SEs in a recent cohort. METHODS Patients with a diagnosis of GCA between May 2009 and March 2018 were included in this multicentric retrospective study. Characteristics of patients, treatment modalities and GC-related SEs were collected and analysed. Risk factors associated with the occurrence of SE were studied. RESULTS We analysed the files from 206 patients (153 women, 53 men; median age 74 years). Median follow-up was 34 months. Patients received GC for a median of 25 months, starting at 0.7 mg/kg/day, with tapering to 5 mg/day after 11 months follow-up. Flares occurred in 83/201 (41%) patients. Among the 132 patients who stopped GC, 29 (22%) experienced a relapse. SEs occurred in 129 (64%) patients: bone fractures and infections in 13% each and hypertension onset in 9%. Age >75 years, treatment duration >2 years, past medical history of diabetes were risk factors associated with GC-related SEs. CONCLUSIONS Flares occur in 41% of patients during GC withdrawal. As much as 64% of patients had treatment related SEs. An age> 75 year and a past medical history of diabetes were predictive of SEs during follow-up.
CD11c participates in triggering acute graft‐versus‐host disease during bone marrow transplantation

CD11c is a canonical dendritic cell (DC) marker with poorly defined functions in the immune system. Here, we found that blocking CD11c on human peripheral blood mononuclear cell‐derived DCs (MoDCs) inhibited the proliferation of CD4+ T cells and the differentiation into IFN‐γ‐producing T helper 1 (Th1) cells, which were critical in acute graft‐versus‐host disease (aGVHD) pathogenesis. Using allogeneic bone marrow transplantation (allo‐BMT) murine models, we consistently found that CD11c‐deficient recipient mice had alleviated aGVHD symptoms for the decreased IFN‐γ‐expressing CD4+ Th1 cells and CD8+ T cells. Transcriptional analysis showed that CD11c participated in several immune regulation functions including maintaining antigen presentation of APCs. CD11c‐deficient bone marrow‐derived DCs (BMDCs) impaired the antigen presentation function in coculture assay. Mechanistically, CD11c interacted with MHCII and Hsp90 and participated in the phosphorylation of Akt and Erk1/2 in DCs after multiple inflammatory stimulations. Therefore, CD11c played crucial roles in triggering aGVHD and might serve as a potential target for the prevention and treatment of aGVHD.
Intramuscular adipose tissue at level Th12 is associated with survival in COVID‐19

Body composition refers to the amount and distribution of skeletal muscle, adipose tissue and bone in the human body. Sarcopenia, as an example of abnormal body composition, is defined as a significant loss of skeletal muscle mass (muscle wasting) and muscle strength and infiltration of muscle by fat and connective tissue. Body composition has been studied using a single computed tomography (CT) slice, which is considered the reference standard for quantitative body composition studies. Abnormal body composition, and in particular sarcopenia, has been associated with survival in patients with cancer or an increased cardiometabolic risk. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of coronavirus disease 19 (COVID-19). In COVID-19 patients, age is associated with lower survival, and a higher body mass index (BMI) is associated with invasive ventilation. Regarding abnormal body composition, an increase of visceral fat has been associated with ICU admission of COVID-19 patients. Effects of abnormal body composition on survival are currently unknown. We hypothesized that abnormal body composition, as measured on standard chest CT images, is associated with lower survival in COVID-19 patients. The aim of our study was to examine the association between body composition measures and survival in COVID-19 patients.
A New Approach for Accurate Prediction of the Phase Behavior of the Complex Mixtures of Acid Gases, Hydrocarbons, Water, and Methanol in the Petroleum Industry

In this work a new approach for accurate prediction of the vapor-liquid equilibrium of the complex mixtures of water, methanol, acid gases (H2S, CO2), and hydrocarbons considering the hydrogen bonding association, hydrolytic dissociation, and acid gas solvation effects is presented. The overall average absolute deviation between the predicted and measured compositions regarding 330 sour gas mixtures is about 3.22%. The proposed CPA/electrolyte model is quite reliable over wide ranges of temperatures and sour gas concentrations and can be employed for accurate design of sour natural treatment and flow assurance systems in oil and gas industries.
Dynamic contrast‐enhanced magnetic resonance imaging for differentiating head and neck paraganglioma and schwannoma

Morphological assessment with conventional magnetic resonance imaging (MRI) sequences has limited specificity to distinguish between paragangliomas and schwannomas. Assessing the differences in microvascular properties through pharmacokinetic parameters of dynamic contrast‐enhanced (DCE)‐MRI can provide additional information to aid in this differentiation.
Incidence and predictors of vascular events following end‐stage kidney disease in childhood

Cardiovascular death is a leading cause of mortality in paediatric end‐stage kidney disease (ESKD). There is however little known about the clinically relevant vascular disease in this population. We aimed to describe the incidence of new onset vascular disease and vascular death in Australian children receiving renal replacement therapy (RRT). We also aimed to identify demographic or childhood risk factors for these endpoints, and whether vascular disease predicts mortality.