Miracle-dz/UniFAR-FTUs huggingface dataset:
LC-MS/MS Determination of Modified Nucleosides in The Urine of Parkinson’s Disease and Parkinsonian Syndromes Patients

Epigenetic modifications play a key role in gene regulation and expression and are involved in numerous cellular processes. Due to the limited research on nucleosides in Parkinson’s disease (PD), it is very important to consider epigenetic factors and their role in the development of PD. The aim of this study was to investigate and compare the levels of modified nucleosides, such as O-methylguanosine, N6-methyl-2′-deoxyadenosine, 1-methyladenosine, 1-methylguanine, 7-methylguanine, 3-methyladenine and 7-methylguanosine in the urine of Parkinson’s disease (PD) patients and the control group, and to verify that the results obtained differ in a subgroup of patients with parkinsonian syndromes. The study group comprised 18 patients with diagnosed idiopathic Parkinson’s disease and four parkinsonian syndromes. The control group consisted of 30 age- and sex-matched neurological patients without confirmation by neuroimaging brain damage and extrapyramidal symptoms. The levels of nucleosides were determined by validated liquid chromatography coupled with the mass spectrometry (LC-MS/MS) method using the multiple reaction monitoring (MRM) mode. Lower levels of O-methylguanosine, 3-methyladenine, 1-methylguanine, N6-methyl-2′-deoxyadenosine and a higher level of 7-methylguanine in the urine of 22 PD patients were observed. Moreover, elevated levels of 1-methyladenosine, 7-methylguanine, and O-methylguanosine were observed in the parkinsonian syndrome subgroup. These preliminary results may indicate that modified nucleosides describe metabolic disturbances in the metabolism of purine, which was the most severely affected pathway that mediated the detrimental effects of neuroinflammation on PD.
FOLFIRINOX for Recurrent Pancreatic Cancer After Pancreatic Resection: A Secondary Analysis of the Nationwide Multicenter Observational Study Conducted by the Japan Adjuvant Study Group of Pancreatic Cancer 06.

OBJECTIVES The multidrug regimen with fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is widely used for recurrent pancreatic cancer after pancreatic resection. However, there are concerns about severe toxicities and poor tolerability of FOLFIRINOX in these patients because some suffer from surgery-associated malnutrition, weight loss, and diabetes mellitus. We evaluated the toxicity and tolerability of FOLFIRINOX in these patients. METHODS This study was conducted as a secondary analysis of the Japan Adjuvant Study Group of Pancreatic Cancer 06 study, which was a multicenter observational study of FOLFIRINOX for pancreatic cancer in Japan. The toxicity and tolerability of FOLFIRINOX in recurrent disease correlated with those of both the locally advanced and the metastatic disease group. RESULTS The major grades 3 and 4 toxicities observed in the recurrent and locally advanced or metastatic disease groups were neutropenia (68% vs 63%), febrile neutropenia (4% vs 15%, P = 0.007), thrombocytopenia (4% vs 3%), diarrhea (4% vs 8%), and sensory neuropathy (0% vs 2%). The dose modification and relative dose intensity did not differ markedly between the groups. CONCLUSIONS The toxicity and tolerability of FOLFIRINOX for recurrence after pancreatic resection were similar to those for locally advanced or metastatic disease with appropriate patient selection and dose modifications.
Effects of Custom-made Mouthguards on Cardiopulmonary Exercise Capacity

Abstract The importance of using mouthguards as well as their low acceptance rate have been demonstrated. The aim of this study was to investigate the influence of customized mouthguards on hemodynamics. This randomized crossover study used data from 13 subjects (23.5±1.4 years). The cardiopulmonary and metabolic parameters were observed during ergometer tests without mouthguard (control) in comparison to two types of mouthguards (with and normal without breathing channels). Maximum ventilation was significantly decreased with the normal mouthguard (113.3±30.00 l ∙ min−1) in contrast to the mouthguard with breathing channels (122.5±22.9 l ∙ min−1) and control (121.9±30.8 l ∙ min−1). Also the inspiration time was longer when using the normal mouthguard (0.70±0.11 s) compared to the mouthguard with breathing channels (0.63±0.11 s) and control (Co 0.64±0.10 s). Lactate was also increased under the influence of the mouthguard with breathing channels (10.72±1.4 mmol ∙ l−1) compared to the control (9.40±1.77 mmol ∙ l−1) and the normal mouthguard (9.02±1.67 mmol ∙ l−1). In addition, stroke volume kinetics (p=0.048) and maximum heart rates (p=0.01) show changes. Despite equal levels of oxygen uptake and performances under all three conditions, the use of mouthguards showed differences in cardiopulmonary parameters. The use of mouthguards during exercise does not affect physical performance and can be recommended for injury prevention.
Evaluating sensory profiles in nociplastic chronic low back pain: a cross-sectional validation study

ABSTRACT Background Sensory profiles (SPs) may be useful in classifying patients based on sensory sensitivity and behavioral responses to stimuli to develop personalized treatments for nonspecific chronic low back pain (CLBP). The Adolescent/Adult Sensory Profile (AASP) identifies four sensitivity and behavioral response-related quadrants: Sensory Sensitive, Sensation Avoiding, Low Registration, and Sensation Seeking. It is an appropriate questionnaire for evaluating SPs; however, it has not been validated in CLBP. Objectives To assess the internal consistency, test–retest reliability, agreement, and construct validity of the AASP in a CLBP population with nociplastic pain in primary care physiotherapy. Design Two evaluations were performed at a 2-week interval in this non-experimental cross-sectional study. Participants Patients with CLBP. Methods Questionnaires were used to compare outcomes with the AASP. Reliability was evaluated by assessing internal consistency and test–retest reliability. Construct validity was evaluated in response to the a priori hypothesis. Results Ninety patients with CLBP were included. Internal consistency was excellent for all SPs (Cronbach’s alpha, 0.91–0.92). Test–retest reliability Intraclass Correlation Coefficient (ICC (3,2)) 0.82–0.87, for the SPs (95% CI 0.74–0.91, p< .001). Construct validity correlated positively with Low Registration, Sensory Sensitive, and Sensation Avoiding and negatively with Sensation Seeking. Conclusion The AASP is suitable for evaluating SPs in primary care CLBP patients.
Seroprevalence and Molecular Characterization of Coxiella burnetii in Cattle in the Republic of Korea

This study was conducted to determine the prevalence of Coxiella burnetii in cattle and how that prevalence is influenced by cattle breed and growth type. A total of 491 cattle [cattle breed: 216 dairy cattle and 275 beef cattle; growth type: indoor housed (n = 294) and grazing (n = 197)] were used. The presence of C. burnetii DNA and antibodies was detected from blood and serum samples using polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The overall prevalence of C. burnetii was: 10.8% (95% CI: 8.0–13.5%) using PCR and 8.8% (95% CI: 6.3–11.3%) using ELISA. The prevalence of C. burnetii was significantly higher in beef cattle than in dairy cattle using both PCR (13.5% vs. 7.4%; P = 0.032) and ELISA (14.5% vs. 1.4%; P = 0.000), respectively. Comparison by growth type revealed that C. burnetii infection was significantly higher in grazing cattle than in housed cattle when using both PCR (24.9% vs. 1.4%; P = 0.000) and ELISA (21.3% vs. 0.3%; P = 0.000). Beef cattle were at a significantly higher risk of contracting C. burnetii compared with dairy cattle (odds ratio = 3.20, 95% CI: 1.80–5.67; P = 0.000). The risk of contracting C. burnetii in grazing cattle was increased by 32.57-fold (95% CI: 12.84–82.61; P = 0.000) compared with indoor housed cattle. The phylogenetic analysis based on the IS1111 gene revealed that our sequences grouped with human, tick, goat, and cattle isolates/strains found in several countries. C. burnetii sequences circulating in the Republic of Korea exhibit genetic variations. Thus, grazing is a high risk factor for the prevalence and transmission of C. burnetii.
Contrast-Induced Encephalopathy After Endovascular Thrombectomy for Acute Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose: Contrast-induced encephalopathy (CIE) is a rare and underrecognized complication after endovascular thrombectomy (EVT) for acute ischemic stroke. This study investigated the incidence and risk factors of CIE in patients who underwent EVT. Methods: Consecutive patients with acute ischemic stroke who received EVT between September 2014 and December 2019 at 2 medical centers were included. CIE was diagnosed on clinical criteria of neurological deterioration or delayed improvement within 24 hours after the procedure that was unexplained by the infarct or hemorrhagic transformation and radiological criterion of edematous change extending beyond the infarct core accompanied by contrast staining. Results: Of 421 patients with acute ischemic stroke who received EVT, 7 (1.7%) developed CIE. The manifestations included worsening of focal neurological signs, coma, and seizure. Patients with CIE were more likely to experience contrast-induced acute kidney injury than were those without CIE, but the volume of contrast medium was comparable between the two groups. The independent risk factors for CIE included renal dysfunction (defined as an estimated glomerular filtration rate <45 mL/min per 1.73 m2; odds ratio, 5.77 [95% CI, 1.37–24.3]; P=0.02) and history of stroke (odds ratio, 4.96 [95% CI, 1.15–21.3]; P=0.03). Patients with CIE were less likely to achieve favorable functional outcomes (odds ratio, 0.09 [95% CI, 0.01–0.87]; P=0.04). Conclusions: CIE should be suspected in patients with clinical worsening after EVT accompanied by imaging evidence of contrast staining and edematous changes, especially in patients with renal dysfunction or history of stroke.
Naught all zeros in sequence count data are the same

Due to the advent and utility of high-throughput sequencing, modern biomedical research abounds with multivariate count data. Yet such sequence count data is often extremely sparse; that is, much of the data is zero values. Such zero values are well known to cause problems for statistical analyses. In this work we provide a systematic description of different processes that can give rise to zero values as well as the types of methods for addressing zeros in sequence count studies. Importantly, we systematically review how various models perform on each type of zero generating process. Our results demonstrate that zero-inflated models can have substantial biases in both simulated and real data settings. Additionally, we find that zeros due to biological absences can, for many applications, be approximated as originating from under sampling. Beyond these results, this work provides a paired categorization scheme for models and zero generating processes to facilitate discussions and future research into the analysis of sequence count data.
How to Utilize Clinical and Genetic Information for Personalized Treatment of Major Depressive Disorder: Step by Step Strategic Approach

Depression is the single largest contributor to non-fatal health loss and affects 322 million people globally. The clinical heterogeneity of this disorder shows biological correlates and it makes the personalization of antidepressant prescription an important pillar of treatment. There is increasing evidence of genetic overlap between depression, other psychiatric and non-psychiatric disorders, which varies across depression subtypes. Therefore, the first step of clinical evaluation should include a careful assessment of psychopathology and physical health, not limited to previously diagnosed disorders. In part of the patients indeed the pathogenesis of depression may be strictly linked to inflammatory and metabolic abnormalities, and the treatment should target these as much as the depressive symptoms themselves. When the evaluation of the symptom and drug tolerability profile, the concomitant biochemical abnormalities and physical conditions is not enough and at least one pharmacotherapy failed, the genotyping of variants in CYP2D6/CYP2C19 (cytochromes responsible for antidepressant metabolism) should be considered. Individuals with altered metabolism through one of these enzymes may benefit from some antidepressants rather than others or need dose adjustments. Finally, if available, the polygenic predisposition towards cardio-metabolic disorders can be integrated with non-genetic risk factors to tune the identification of patients who should avoid medications associated with this type of side effects. A sufficient knowledge of the polygenic risk of complex medical and psychiatric conditions is becoming relevant as this information can be obtained through direct-to-consumer genetic tests and in the future it may provided by national health care systems.
Function of a viral genome packaging motor from bacteriophage T4 is insensitive to DNA sequence

Abstract Many viruses employ ATP-powered motors during assembly to translocate DNA into procapsid shells. Previous reports raise the question if motor function is modulated by substrate DNA sequence: (i) the phage T4 motor exhibits large translocation rate fluctuations and pauses and slips; (ii) evidence suggests that the phage phi29 motor contacts DNA bases during translocation; and (iii) one theoretical model, the ‘B-A scrunchworm’, predicts that ‘A-philic’ sequences that transition more easily to A-form would alter motor function. Here, we use single-molecule optical tweezers measurements to compare translocation of phage, plasmid, and synthetic A-philic, GC rich sequences by the T4 motor. We observed no significant differences in motor velocities, even with A-philic sequences predicted to show higher translocation rate at high applied force. We also observed no significant changes in motor pausing and only modest changes in slipping. To more generally test for sequence dependence, we conducted correlation analyses across pairs of packaging events. No significant correlations in packaging rate, pausing or slipping versus sequence position were detected across repeated measurements with several different DNA sequences. These studies suggest that viral genome packaging is insensitive to DNA sequence and fluctuations in packaging motor velocity, pausing and slipping are primarily stochastic temporal events.
Examining patient characteristics and HIV-related risks among women with syphilis as indicators for pre-exposure prophylaxis in a nurse-led program (PrEP-RN)

Current HIV pre-exposure prophylaxis (PrEP) guidelines primarily target men who have sex with men (MSM) as candidates for HIV prevention; however, such recommendations often come at the expense of other ethnic and gender minorities, including women. To address barriers to PrEP care among non-MSM, we developed and implemented the first nurse-led PrEP program in Canada, known as PrEP-RN. As part of PrEP-RN, patients who meet objective indicators of HIV risk are offered a referral for PrEP, regardless of sexual orientation. One such measure is syphilis, which has increased in incidence among various population groups and is known to cause biological vulnerabilities to HIV. To better understand HIV-related risks and assess intentions for PrEP use among women, we undertook an 18-month retrospective review of syphilis diagnoses within this group in Ottawa, Canada. As part of this review, we examined 23 patient files, noting their unique characteristics, socio-behavioural risk factors, and noted barriers to PrEP uptake. While none of the women diagnosed with syphilis were diagnosed with HIV, the findings raise some important considerations to facilitate opportunities for HIV prevention among non-MSM, which must take into consideration individual risk practices, sexual health histories, and population groups.
The Innate Immune Signalling Pathways: Turning RIG-I Sensor Activation against Cancer

Simple Summary The clinical success in immunotherapy has been remarkable, and, at the same time, disappointing. The immune context of the tumour microenvironment has an influence on tumour initiation, response, and therapy. It is an urgent matter to explore mechanisms shaping the tumour microenvironment for further progression of immunotherapy. The immunoreceptor retinoic acid-induced gene-I (RIG-I) has emerged as a promising target molecule to activate adoptive immunity via activation of innate immunity. In this paper, we highlight basic mechanisms of RIG-I signalling in the tumour microenvironment, broadening to the most recent preclinical studies that employ RIG-I agonists. We also present an up-to-date selection of clinical trials designed to prove the antitumour role of RIG I, and that may result in improved therapeutic outcomes for cancer patients. Abstract Over the last 15 years, the ability to harness a patient’s own immune system has led to significant progress in cancer therapy. For instance, immunotherapeutic strategies, including checkpoint inhibitors or adoptive cell therapy using chimeric antigen receptor T-cell (CAR-T), are specifically aimed at enhancing adaptive anti-tumour immunity. Several research groups demonstrated that adaptive anti-tumour immunity is highly sustained by innate immune responses. Host innate immunity provides the first line of defence and mediates recognition of danger signals through pattern recognition receptors (PRRs), such as cytosolic sensors of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular pattern (DAMP) signals. The retinoic acid-inducible gene I (RIG-I) is a cytosolic RNA helicase, which detects viral double-strand RNA and, once activated, triggers signalling pathways, converging on the production of type I interferons, proinflammatory cytokines, and programmed cell death. Approaches aimed at activating RIG-I within cancers are being explored as novel therapeutic treatments to generate an inflammatory tumour microenvironment and to facilitate cytotoxic T-cell cross-priming and infiltration. Here, we provide an overview of studies regarding the role of RIG-I signalling in the tumour microenvironment, and the most recent preclinical studies that employ RIG-I agonists. Lastly, we present a selection of clinical trials designed to prove the antitumour role of RIG I and that may result in improved therapeutic outcomes for cancer patients.
Self-care strategies in response to nurses’ moral injury during COVID-19 pandemic

These are strange and unprecedented times in the wake of the COVID-19 pandemic. Most frontline healthcare professionals have never witnessed anything like this before. As a result, staff may experience numerous and continuous traumatic events, which in many instances, will negatively affect their psychological well-being. Particularly, nurses face extraordinary challenges in response to shifting protocols, triage, shortages of resources, and the astonishing numbers of patients who require care in expedited time constraints. As most healthcare workers are passionate nursing professionals, frustration and often a sense of powerlessness occur when they find themselves unable to provide needed care to their patients. The overwhelming number of deaths, patients isolated and dying alone, and the ever-present fear of being infected and then infecting colleagues, family, friends due to the lack of protective gear or known protocols takes its toll on emotional and psychological well-being. For nurses, the experience of this significant (hopefully once-in-a-lifetime) event can inflict on-going moral injury. Nurses affected by this trauma require education, coping tools, and therapy to help avoid or alleviate the adverse effects on their well-being. Institutions must provide these resources to tend to the well-being of their healthcare staff, during and beyond the pandemic. This article aims to investigate moral distress—considering it as a moral injury—and offer tools and recommendations to support healthcare nurses as they respond to this crisis and its aftermath.
Associations Between Peer Use, Costs and Benefits, Self-Efficacy, and Adolescent E-cigarette Use.

OBJECTIVE Prior research identified peer use as a salient risk factor of adolescent electronic cigarette (e-cigarette) use, but has not expanded on the mechanisms of this association. METHODS Participants were 562 adolescents recruited from rural and suburban public high schools and an adolescent medicine clinic in the mid-Atlantic United States. Participants completed a packet of questionnaires that assessed demographics, substance use, expectations about the consequences of e-cigarette use, and perceptions of their own self-efficacy to resist using e-cigarettes. We estimated a series of mediation models using the MODEL INDIRECT command in MPLUS statistical software. In all models, significance of indirect effects from peer e-cigarette use to self-reported e-cigarette use were tested via two variables: (a) expected costs, (b) benefits of e-cigarette use, and (c) the perceived self-efficacy of the individual to refrain from e-cigarette use. RESULTS Adolescents with more peers using e-cigarettes were more likely to have ever used an e-cigarette and perceived greater benefits and fewer costs, which was associated with a reduced self-efficacy to refrain from e-cigarette smoking (Model 1). Those with more peers using e-cigarettes were more likely to be currently using e-cigarettes themselves because they perceived greater benefits and fewer costs, which was associated with a reduced self-efficacy to refrain from e-cigarette smoking (Model 2). CONCLUSION Peer use, self-efficacy to resist use, and expectations of cost and benefits of e-cigarette use should be considered as possible targets when devising tailored interventions and policies to prevent or reduce negative health consequences of long-term e-cigarette use.
High-fat diet reduces the level of secretory immunoglobulin A coating of commensal gut microbiota

Excessive fat intake is associated with changes in gut microbiota composition. In the present study, we focused on the secretory immunoglobulin A (SIgA) coating of gut microbiota as a mucosal immune response affecting the gut microbiota following a high-fat diet (HFD). The level of SIgA coating of gut microbiota was evaluated in normal-fat diet (NFD)- and HFD-fed mice. HFD significantly decreased the level of SIgA coating the gut microbiota compared with NFD. Of note, substitution of HFD with NFD resulted in a complete recovery of the level of SIgA coating. These findings suggest that dietary fat influences the SIgA coating of the gut microbiota. Furthermore, we analyzed the composition of the gut microbiota and the concentration of cecal short-chain fatty acids. HFD feeding changed the gut microbiota composition at the phylum and family levels. Pearson correlation analysis between the level of SIgA coating of gut microbiota and the relative abundance of gut microbiota showed that the relative abundances of Clostridiaceae, Mogibacteriaceae, Turicibacteraceae, and Bifidobacteriaceae were negatively correlated with the level of SIgA coating of gut microbiota. Conversely, the relative abundances of Desulfovibrionaceae, S24-7, and Lactobacillaceae were positively correlated with the level of SIgA coating. The concentrations of cecal acetate and butyrate were lower in HFD-fed mice and positively correlated with the level of SIgA coating of gut microbiota. Our observations suggest that a decrease in the level of SIgA coating of the gut microbiota through a HFD might relate to HFD-induced changes in microbial composition and microbial metabolites production.