Miracle-dz/UniFAR-FTUs huggingface dataset:
Eliminating Postoperative Radiation to the Pathologically Node-Negative Neck: Long-Term Results of a Prospective Phase II Study.

PURPOSE The volume treated with postoperative radiation therapy (PORT) is a mediator of toxicity, and reduced volumes result in improved quality of life (QOL). In this phase II trial, treatment volumes were reduced by omitting PORT to the pathologically negative (PN0) neck in patients with primary head and neck squamous cell carcinoma. METHODS Patients with head and neck squamous cell carcinoma who underwent surgical resection and neck dissection with a PN0 neck and high-risk features mandating PORT to the primary and/or involved neck were eligible. The primary end point was greater than 90% disease control in the unirradiated neck. QOL was evaluated using the MD Anderson Dysphagia Inventory and the University of Michigan patient-reported xerostomia questionnaire. RESULTS Seventy-three patients were enrolled, and 72 were evaluable. Median age was 56 years (range, 31 to 81 years); 58 patients were male, and 47 (65%) had a smoking history. Sites included oral cavity (n = 14), oropharynx (n = 37), hypopharynx (n = 4), larynx (n = 16), and unknown primary tumor (n = 1). According to the American Joint Committee on Cancer Staging Manual (7th edition), 67 patients (93%) had stage III/IV disease, and 71% of tumors involved or crossed midline. No patient had contralateral neck PORT. In 17 patients (24%), only the primary site was treated. At a median follow-up of 53 months, two patients experienced treatment failure of the PN0 unirradiated neck; they also experienced treatment failure locally. Unirradiated neck control was 97% (95% CI, 93.4% to 100.0%). Five-year rates of local control, regional control, progression-free survival, and overall survival were 84%, 93%, 60%, and 64%, respectively. QOL measures were not significantly different from baseline at 12 and 24 months post-PORT (P > .05). CONCLUSION Eliminating PORT to the PN0 neck resulted in excellent control rates in the unirradiated neck without long-term adverse effects on global QOL.
Development of a 3D multibody system of the human lumbar spine

Development of a 3D multibody system of the human lumbar spine In the present work, a three-dimensional multibody model of the lumbar spine was developed to analyse the force and torques that each intervertebral disc (IVD) is subjected during daily movements. The first work’s stage summarizes the literature review of the state-of-the-art of the multibody models of the spine. It was also characterized the anatomy of the spine, detailing at the vertebrae of the lumbar spine and sacrum, the facet joints, the intervertebral disc and the ligaments. The model is composed by five intervertebral discs, six vertebrae (L1 to S1), ligaments and facet joints. The vertebrae were simulated as rigid bodies, the intervertebral discs as bushing elements (with six degree-of-freedom), the ligaments as spring elements and the facet joints as separators. The spring constant of the bushing elements were characterized using data from a Finite Elements dedicated software, developed under the research project in which this work is inserted. To characterize the spring constant of the ligaments a curve of force-deformation found in the literature was used. After the model validation (with data found in the literature), it was possible to see how the force/torque is distributed along the intervertebral discs during several simulated movements: flexion, extension, lateral bending, axial rotation, traction and compression. Besides a healthy lumbar spine, it was also simulated a spine with fusion of L4L5 to calculate the percentage of variation of the force/torque that each IVD is subjected comparing with the healthy spine. Key-words: multibody systems, lumbar spine, intervertebral disc, bushing element, movement analysis
Health Care Processes Contributing to Suicide Risk in Veterans During and After Residential Substance Abuse Treatment

Abstract Objective: Substance use disorders are an important risk factor for suicide. While residential drug treatment programs improve clinical outcomes for substance use disorders, less is known about the role of related health care processes in contributing to suicide risk. These data may help to inform strategies to prevent suicide during and after residential treatment. Methods: A retrospective analysis was conducted on root-cause analysis (RCA) reports of suicide in veterans occurring within 3 months of discharge from a residential drug treatment program that were reported to a Veterans Affairs facility between 2001 and 2017. Demographic information such as age, gender, and psychiatric comorbidity were abstracted from each report. In addition, an established codebook was used to code root causes from each report. Root causes were grouped into categories in order to characterize the key system and organizational-level processes that may have contributed to the suicide. Results: A total of 39 RCA reports of suicide occurring within 3 months after discharge from a residential drug treatment program were identified. The majority of decedents were men and the average age was 42.9 years (SD = 11.2). The most common method of suicide was overdose (33%) followed by hanging (28%). Most suicides occurred in close proximity to discharge, with 56% (n = 22) occurring within seven days of discharge and 36% (n = 14) occurring within 48 hours of discharge. The most common substances used by decedents prior to admission were alcohol or opiates. RCA teams identified a total of 140 root causes and the majority were due to problems with suicide risk assessment (n = 32, 22.9%). Non-engagement with treatment during (n = 20, 14.3%) and after the residential stay (n = 18, 12.9%) was also highlighted as an important concern. Finally, several reports raised concerns that a discharge prior to treatment completion or a precipitous discharge due to program violation negatively impacted treatment outcomes. Conclusions: Efforts to prevent suicide in the period following discharge from a residential drug treatment program should focus on addressing suicide risk factors during admission and helping patients engage more fully in substance use disorder treatment.
Rituximab as an adjuvant therapy for pemphigus: experience in 61 patients from a single center with long‐term follow‐up

Rituximab is increasingly being used as an adjuvant treatment for recalcitrant or relapsed pemphigus, but information on its use as a first‐line agent is limited. We describe the long‐term effectiveness and safety of rituximab in the treatment of pemphigus and compare the treatment outcomes when rituximab is used as first‐line treatment vis‐à‐vis after treatment failure or relapse.
Problematic smartphone use associated with greater alcohol consumption, mental health issues, poorer academic performance, and impulsivity

Background This study sought to examine the occurrence of the problematic use of smartphones in a university sample and associated physical and mental health correlates, including potential relationships with risky sexual practices. Methods A 156-item anonymous online survey was distributed via e-mail to a sample of 9,449 university students. In addition to problematic smartphone usage, current use of alcohol and drugs, psychological and physical status, and academic performance were assessed. Results A total of 31,425 participants were included in the analysis, of whom 20.1% reported problematic smartphone use. Problematic use of smartphones was associated with lower grade point averages and with alcohol use disorder symptoms. It was also significantly associated with impulsivity (Barratt scale and ADHD) and elevated occurrence of PTSD, anxiety, and depression. Finally, those with current problems with smartphone use were significantly more sexually active. Conclusions Problematic use of smartphones is common and has public health importance due to these demonstrable associations with alcohol use, certain mental health diagnoses (especially ADHD, anxiety, depression, and PTSD), and worse scholastic performance. Clinicians should enquire about excessive smartphone use as it may be associated with a range of mental health issues. Research is needed to address longitudinal associations.
EternaBrain: Automated RNA design through move sets and strategies from an Internet-scale RNA videogame

Emerging RNA-based approaches to disease detection and gene therapy require RNA sequences that fold into specific base-pairing patterns, but computational algorithms generally remain inadequate for these secondary structure design tasks. The Eterna project has crowdsourced RNA design to human video game players in the form of puzzles that reach extraordinary difficulty. Here, we demonstrate that Eterna participants’ moves and strategies can be leveraged to improve automated computational RNA design. We present an eternamoves-large repository consisting of 1.8 million of player moves on 12 of the most-played Eterna puzzles as well as an eternamoves-select repository of 30,477 moves from the top 72 players on a select set of more advanced puzzles. On eternamoves-select, we present a multilayer convolutional neural network (CNN) EternaBrain that achieves test accuracies of 51% and 34% in base prediction and location prediction, respectively, suggesting that top players’ moves are partially stereotyped. Pipelining this CNN’s move predictions with single-action-playout (SAP) of six strategies compiled by human players solves 61 out of 100 independent puzzles in the Eterna100 benchmark. EternaBrain-SAP outperforms previously published RNA design algorithms and achieves similar or better performance than a newer generation of deep learning methods, while being largely orthogonal to these other methods. Our study provides useful lessons for future efforts to achieve human-competitive performance with automated RNA design algorithms.
Radiofrequency ablation guided by cone beam computed tomography for hepatocellular carcinoma: a comparative study of clinical results with the conventional spiral computed tomography-guided procedure

Objective To compare the outcomes of cone beam computed tomography (CBCT)-guided radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) with those of traditional spiral computed tomography (s-CT)-guided RFA. Methods This retrospective study analysed data from patients with HCC that underwent RFA guided by either CBCT or s-CT. A number of preoperative and postoperative characteristics, including operation time, ablation time, radiation dose and hospital stay were recorded for all patients. The incidence of intraoperative and postoperative complications was recorded. The therapeutic effect was evaluated at 1, 3 and 6 months after RFA. Results A total of 47 patients with HCC (12 females and 35 males) underwent successful RFA: 21 underwent CBCT-guided RFA and 26 underwent s-CT-guided RFA. Except for one case of pneumothorax in the s-CT group, no serious complications occurred. The objective response rate and disease control rate at 1, 3 and 6 months after RFA showed no significant differences between the two groups. Throughout the 6-month follow-up period, the complete ablation rate was 19 of 21 patients (90.5%) in the CBCT group and 19 of 26 patients (73.1%) in the s-CT group. Conclusions CBCT was a safe and effective guiding modality for RFA in patients with HCC.
Characteristics of olfactory ensheathing cells and microarray analysis in Tupaia belangeri (Wagner, 1841)

Tree shrews are most closely related to the primates and so possess a number of advantages in experimental studies; they have been used as an animal model in bacterial and virus infection, cancer, endocrine system disease, and certain nervous system diseases. Their olfactory ensheathing cells (OECs) are able to release several cytokines to promote neuronal survival, regeneration and remyelination. The present study used western blot analysis to identify antibody specificity in protein extracts from whole tree shrew brains to identify the specificity of p75 nerve growth factor receptor (NGFR) derived from rabbits (75 kDa). OECs were cultured and isolated, then stained and identified using the antibodies for p75NGFR. To investigate the capacity of OECs to express cytokines and growth factors, microarray technology was used, and the analysis revealed that OECs were able to express 9,821 genes. Of these genes, 44 genes were from the neurotrophic factor family, which may indicate their potential in transplantation in vivo. The present study considered the function of OECs as revealed by other studies, and may contribute to future research.
Specific Viral Etiologies Are Associated With Outcomes in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES Infectious pneumonia is the most common cause of acute respiratory distress syndrome, with viruses frequently implicated as causative. However, the significance of viruses in pediatric acute respiratory distress syndrome is unknown. We aimed to characterize the epidemiology of viral pneumonia in pediatric acute respiratory distress syndrome and compare characteristics and outcomes between pneumonia subjects with and without viruses. Secondarily, we examined the association between specific viruses and outcomes. DESIGN We performed a secondary analysis of a prospectively enrolled pediatric acute respiratory distress syndrome cohort. Subjects with pneumonia acute respiratory distress syndrome underwent testing of respiratory secretions for viruses and culture for bacteria and fungi and were stratified according to presence or absence of a virus. SETTING Tertiary care children's hospital. PATIENTS Children with acute respiratory distress syndrome. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Of 544 children with acute respiratory distress syndrome, 282 (52%) had pneumonia as their inciting etiology, of whom 212 were virus-positive. In 141 of 282 (50%) pneumonia acute respiratory distress syndrome cases, a virus was the sole pathogen identified. Virus-positive pneumonia had fewer organ failures but worse oxygenation, relative to virus-negative pneumonia, with no differences in antibiotic use, ventilator duration, or mortality. Subjects with respiratory syncytial virus-associated acute respiratory distress syndrome had lower mortality (0%), and subjects with influenza-associated acute respiratory distress syndrome had shorter ventilator duration, relative to other viral acute respiratory distress syndrome. Nonadeno herpesviruses, tested for exclusively in immunocompromised subjects, had greater than 80% mortality. CONCLUSIONS Pneumonia was the most common cause of pediatric acute respiratory distress syndrome, and viruses were commonly isolated as the sole pathogen. Respiratory syncytial virus and influenza were associated with better outcomes relative to other viral etiologies. Viral pneumonias in immunocompromised subjects, particularly nonadeno herpesviruses, drove the mortality rate for pneumonia acute respiratory distress syndrome. Specific viral etiologies are associated with differential outcomes in pediatric acute respiratory distress syndrome and should be accounted for in future studies.
Combination treatment with auranofin and nutlin-3a induces synergistic cytotoxicity in breast cancer cells

ABSTRACT Auranofin is a gold complex categorized as an anti-rheumatic agent. Recently, several investigators suggested that auranofin may act as a potent anti-cancer drug for breast tumors. Nutlin-3a is a cis-imidazoline analog which prevents interaction between mouse double minute 2 homolog (MDM2) and the tumor suppressor p53. The aim of this study was to examine cell growth inhibition mediated by auranofin or nutlin-3a individually as well as in combination with MCF-7 and MDA-MB-231 cells. To assess any potential synergistic effects between auranofin and nutlin-3a, low concentrations of auranofin and nutlin-3a were simultaneously incubated with MCF-7 and MDA-MB-231 cells. Cell viability assay, caspase-3/7 assay, and poly (ADP-ribose) polymerase cleavage revealed that auranofin and nutlin-3a exerted a synergistic effect on cancer cell apoptosis. Isobologram analysis of MCF-7 and MDA-MB-231 cells noted evident synergism between auranofin and nutlin-3a. The combined treatment increased the expression of mitochondrial pro-apoptotic factors such as Bcl-2 associated X protein and Bcl-2 homologous antagonist/killer. Further, combination treatment signiﬁcantly enhanced reactive oxygen species (ROS) generation in MCF-7 and MDA-MB-231 cells. In conclusion, data demonstrated that combined treatment with auranofin and nutlin-3a exhibited a synergistic action on breast cancer cells and this combination may be considered for use as a novel therapeutic strategy for breast cancer.
Glutathione peroxidase 4 and vitamin E control reticulocyte maturation, stress erythropoiesis and iron homeostasis

Glutathione peroxidase 4 (GPX4) is unique as it is the only enzyme that can prevent detrimental lipid peroxidation in vivo by reducing lipid peroxides to the respective alcohols thereby stabilizing oxidation products of unsaturated fatty acids. During reticulocyte maturation, lipid peroxidation mediated by 15-lipoxygenase in humans and rabbits and by 12/15-lipoxygenase (ALOX15) in mice was considered the initiating event for the elimination of mitochondria but is now known to occur through mitophagy. Yet, genetic ablation of the Alox15 gene in mice failed to provide evidence for this hypothesis. We designed a different genetic approach to tackle this open conundrum. Since either other lipoxygenases or non-enzymatic autooxidative mechanisms may compensate for the loss of Alox15, we asked whether ablation of Gpx4 in the hematopoietic system would result in the perturbation of reticulocyte maturation. Quantitative assessment of erythropoiesis indices in the blood, bone marrow (BM) and spleen of chimeric mice with Gpx4 ablated in hematopoietic cells revealed anemia with an increase in the fraction of erythroid precursor cells and reticulocytes. Additional dietary vitamin E depletion strongly aggravated the anemic phenotype. Despite strong extramedullary erythropoiesis reticulocytes failed to mature and accumulated large autophagosomes with engulfed mitochondria. Gpx4-deficiency in hematopoietic cells led to systemic hepatic iron overload and simultaneous severe iron demand in the erythroid system. Despite extremely high erythropoietin and erythroferrone levels in the plasma, hepcidin expression remained unchanged. Conclusively, perturbed reticulocyte maturation in response to Gpx4 loss in hematopoietic cells thus causes ineffective erythropoiesis, a phenotype partially masked by dietary vitamin E supplementation.
The Challenge of the Sponge Suberites domuncula (Olivi, 1792) in the Presence of a Symbiotic Bacterium and a Pathogen Bacterium

Sponges, which are in close contact with numerous bacteria in prey/predator, symbiotic and pathogenic relationships, must provide an appropriate response in such situations. This starts with a discriminating recognition of the partner either by a physical contact or through secreted molecules or both. We investigated the expression of the Toll-like receptor, Caspase 3/7, Tumor Necrosis Factor receptor-associated factor 6, Bcl-2 homology protein-2 and macrophage expressed genes of axenic sponge cells in the presence of a symbiotic bacterium (Endozoicomonas sp. Hex311), a pathogen bacterium (Pseudoalteromonas sp. 1A1), their exoproducts and lipopolysaccharides. The vast majority of answers are in line with what could be observed with the symbiotic bacterium. The pathogenic bacterium seems to profit from the eukaryotic cell: suppression of the production of the antibacterial compound, inhibition of the apoptosis caspase-dependent pathway, deregulation of bacterial recognition. This work contributes new scientific knowledge in the field of immunology and apoptosis in early branching metazoan harboring within its tissue and cells a large number of symbiotic bacteria.
The glutamine debate in surgery and critical care.

PURPOSE OF REVIEW Glutamine (GLN) is a versatile amino acid, long believed to have important implications in ICU and surgical patients. An extensive body of data examining GLN supplementation of TPN demonstrated a consistent signal of improved outcomes. However, recently signals of risk have come from two large-scale multicenter trials evaluating GLN (and other nutrients) at high dose and as primary pharmaconutrients, not as supplementation to complete nutrition. These trials indicate a risk of increased mortality when GLN is given to patients in shock, renal failure, and early in acute phase of critical care. RECENT FINDINGS Recent literature continues to confirm that low and high admission GLN levels are associated with increased ICU mortality and adverse outcomes. Further, a recent meta-analysis examined trials utilizing GLN-supplemented TPN in stabile ICU patients consistent with current clinical guidelines. This analysis showed GLN supplementation of TPN led to reduced infections, LOS and hospital mortality. SUMMARY Three recent meta-analyses have confirmed traditional GLN-supplemented (or 'GLN-Complemented' - providing GLN for completeness of amino acid content) TPN is safe, reduces mortality and improves outcome in surgical and ICU patients. Patients in need of TPN, burns, trauma or malignancies should continue to benefit from supplemental GLN, administered either intravenously at less than 0.35 g/kg/day or enterally at less than 0.5 g/kg/day. Further, a large trial of EN GLN supplementation in burns is ongoing. Thus, when used per guideline recommendations, the GLN story is likely still relevant to ICU outcomes and research.
Yak-Kong Soybean (Glycine max) Fermented by a Novel Pediococcus pentosaceus Inhibits the Oxidative Stress-Induced Monocyte–Endothelial Cell Adhesion

Yak-Kong (YK), a small black soybean (Glycine max) in Korea, contained higher concentrations of antioxidants than ordinary black soybean or yellow soybean in our previous study. We prepared the fermented YK extract by using a novel lactic acid bacterium, Pediococcus pentosaceus AOA2017 (AOA2017) isolated from Eleusine coracana, and found that the antioxidant ability was enhanced after fermentation. In order to investigate the cause of the enhanced antioxidant ability in the fermented YK extract, we conducted a phenolic composition analysis. The results show that proanthocyanidin decreased and phenolic acids increased with a statistical significance after fermentation. Among the phenolic acids, p-coumaric acid was newly produced at about 11.7 mg/100 g, which did not exist before the fermentation. Further, the fermented YK extract with increased p-coumaric acid significantly inhibited the lipopolysaccharide-induced THP-1 monocyte–endothelial cell adhesion compared to the unfermented YK extract. The fermented YK extract also suppressed the protein expression levels of vascular cell adhesion molecule (VCAM)-1 in human umbilical vein endothelial cells (HUVECs). Together with the previous studies, our results suggest that the extract of YK fermented by AOA2017 has potential to be a new functional food material with its enhanced bioactive compounds which may help to prevent atherosclerosis caused by oxidative stress.