Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of cytochrome P450 3A genetic polymorphisms on tacrolimus pharmacokinetics in ulcerative colitis patients

Tacrolimus (Tac) is an effective remission inducer of refractory ulcerative colitis (UC). Gene polymorphisms result in interindividual variability in Tac pharmacokinetics. In this study, we aimed to examine the relationships between gene polymorphisms and the metabolism, pharmacokinetics, and therapeutic effects of Tac in patients with UC. Forty-five patients with moderate-to-severe refractory UC treated with Tac were retrospectively enrolled. Genotyping for cytochrome P450 (CYP) 3A4*1G, CYP3A5*3, CYP2C19*2, CYP2C19*3, nuclear receptor subfamily 1 group I member 2 (NR1I2)–25385C>T, ATP-binding cassette subfamily C member 2 (ABCC2)–24C>T, ABCC2 1249G>A, and ABCC2 3972C>T was performed. Concentration/dose (C/D) ratio, clinical therapeutic effects, and adverse events were evaluated. The C/D ratio of Tac in UC patients with the CYP3A4*1G allele was statistically lower than in those with the CYP3A4*1/*1 allele (P = 0.005) and significantly lower in patients with CYP3A5*3/*3 than in those with CYP3A5*1 (P < 0.001). Among patients with the CYP3A4*1G allele, the C/D ratio was significantly lower in patients with CYP3A5*1 than in those with CYP3A5*3/*3 (P = 0.001). Patients with the NR1I2–25385C/C genotype presented significantly more overall adverse events than those with the C/T or T/T genotype (P = 0.03). Although CYP3A4*1G and CYP3A5*3 polymorphisms were related to Tac pharmacokinetics, CYP3A5 presented a stronger effect than CYP3A4. The NR1I2–25385C/C genotype was related to the overall adverse events. The evaluation of these polymorphisms could be useful in the treatment of UC with Tac.
Barriers and enablers to effective interprofessional teamwork in the operating room: A qualitative study using the Theoretical Domains Framework

Background Effective teamwork is critical for safe, high-quality care in the operating room (OR); however, teamwork interventions have not consistently resulted in the expected gains for patient safety or surgical culture. In order to optimize OR teamwork in a targeted and evidence-based manner, it is first necessary to conduct a comprehensive, theory-informed assessment of barriers and enablers from an interprofessional perspective. Methods This qualitative study was informed by the Theoretical Domains Framework (TDF). Volunteer, purposive and snowball sampling were conducted primarily across four sites in Ontario, Canada and continued until saturation was reached. Interviews were recorded, transcribed, and de-identified. Directed content analysis was conducted in duplicate using the TDF as the initial coding framework. Codes were then refined whereby similar codes were grouped into larger categories of meaning within each TDF domain, resulting in a list of domain-specific barriers and enablers. Results A total of 66 OR healthcare professionals participated in the study (19 Registered Nurses, two Registered Practical Nurses, 17 anaesthesiologists, 26 surgeons, two perfusionists). The most frequently identified teamwork enablers included people management, shared definition of teamwork, communication strategies, positive emotions, familiarity with team members, and alignment of teamwork with professional role. The most frequently identified teamwork barriers included others’ personalities, gender, hierarchies, resource issues, lack of knowledge of best practices for teamwork, negative emotions, conflicting norms and perceptions across professions, being unfamiliar with team members, and on-call/night shifts. Conclusions We identified key factors influencing OR teamwork from an interprofessional perspective using a theoretically informed and systematic approach. Our findings reveal important targets for future interventions and may ultimately increase their effectiveness. Specifically, achieving optimal teamwork in the OR may require a multi-level intervention that addresses individual, team and systems-level factors with particular attention to complex social and professional hierarchies.
Iron–Sulfur Cluster Protein NITROGEN FIXATION S-LIKE1 and Its Interactor FRATAXIN Function in Plant Immunity1[OPEN]

Iron–sulfur cluster proteins play a role in plant innate immunity by regulating plant defense-related genes. Iron–sulfur (Fe–S) clusters are inorganic cofactors that are present in all kingdoms of life as part of a large number of proteins involved in several cellular processes, including DNA replication and metabolism. In this work, we demonstrate an additional role for two Fe–S cluster genes in biotic stress responses in plants. Eleven Fe–S cluster genes, including the NITROGEN FIXATION S-LIKE1 (NFS1) and its interactor FRATAXIN (FH), when silenced in Nicotiana benthamiana, compromised nonhost resistance to Pseudomonas syringae pv. tomato T1. NbNFS1 expression was induced by pathogens and salicylic acid. Arabidopsis (Arabidopsis thaliana) atnfs and atfh mutants, with reduced AtNFS1 or AtFH gene expression, respectively, showed increased susceptibility to both host and nonhost pathogen infection. Arabidopsis AtNFS1 and AtFH overexpressor lines displayed decreased susceptibility to infection by host pathogen P. syringae pv. tomato DC3000. The AtNFS1 overexpression line exhibited constitutive upregulation of several defense-related genes and enrichment of gene ontology terms related to immunity and salicylic acid responses. Our results demonstrate that NFS1 and its interactor FH are involved not only in nonhost resistance but also in basal resistance, suggesting a new role of the Fe–S cluster pathway in plant immunity.
When infographics work better: the interplay between temporal frame and message format in e-health communication

Abstract Objective This study examined the effects of temporal frame and message format on users’ risk perception, message elaboration, and intention to disseminate the message to others. Methods 268 undergraduate students at a U.S. public university participated in a 2 (temporal frame: day vs. year) x 2 (message format: text-based vs. visual-based infographics) online experiment. Participants were randomly assigned to one of the four conditions and completed questions about perceived risk, message elaboration, intention to share information, and their demographics, and medical history. Results Findings reported that the interaction was significant for all dependent variables: perceived risk, F(1, 264) = 11.46, p < . 01, ηp2 = . 04, message elaboration, F(1, 264) = 8.73, p < . 01, ηp2 = . 03, and sharing intention, F(1, 264) = 11.74, p < . 01, ηp2 = . 04. Conclusion Visual-based infographics were more effective when paired with a day frame, while text-based messages were more influential when used with a year frame
Comparison of Short-term Results after Laparoscopic Complete Mesocolic Excision and Standard Colectomy for Right-Sided Colon Cancer: Analysis of a Western Center Cohort

Purpose Laparoscopic complete mesocolic excision (CME) right colectomy is a technically demanding procedure infrequently employed in Western centers. This retrospective cohort study aims to analyze the safety of laparoscopic CME colectomy compared to standard colectomy for right-sided colon cancer in a Western series. Methods Prospectively collected data from 60 patients who underwent laparoscopic CME right colectomy were compared to the ones of 55 patients who underwent laparoscopic standard right colectomy. Results No differences in clinical characteristics were observed between the CME and standard right colectomy groups. No differences were demonstrated in terms of blood loss (P = 0.060), intraoperative complications (P = 1), conversion rate (P = 0.102), and operative time (P = 0.473). No deaths were observed in either group, while complication rate was 40.0% in the CME and 49.1% in the standard group (P = 0.353). Severe complications occurred in 10.0% vs. 9.1% (P = 0.842), redo surgery in 5.0% vs. 7.3% (P = 0.708), and unplanned readmission in 5.0% vs. 5.5% (P = 1) after CME and standard colectomy, respectively. A significant difference in favor of CME was observed in the total length of specimen (P < 0.001), proximal (P = 0.018), and distal margins (P = 0.037). The number of lymph nodes harvested was significantly higher in the CME group (27 vs. 22, P = 0.037). Conclusion In Western series, where patients have less favorable clinical characteristics, laparoscopic CME allows to obtain better quality surgical specimens and comparable short-term outcomes compared to standard right colectomy.
Chitosan bis(halophenylcarbamate)-(isobutyrylamide) based chiral stationary phases for enantiomeric separation

The goal of the present study is to systematically investigate the enantioseparation performance and eluent tolerance of chiral stationary phases (CSPs) derived from chitosan bis(halophenylcarbamate)-(isobutyrylamide)s. Hence, N-isobutyrylated chitosan was prepared from completely deacetylated chitosan with a high molecular weight. The N-isobutyrylated chitosan was further derivatized with various halo-substituted phenyl isocyanates, consequently affording a series of chitosan bis(halophenylcarbamate)-(isobutyrylamide)s, which were coated onto 3-aminopropyl silica particles to obtain a class of CSPs. The chiral recognition ability of these CSPs was evaluated with nineteen racemates. It was found that the chitosan bis(halophenylcarbamate)-(isobutyrylamide)s showed powerful enantioseparation performance, and those with 4-chlorophenylcarbamate, 3,4-dichlorophenylcarbamate and 4-trifluoromethoxyphenylcarbamate seemed to exhibit comparable or even more superior enantioseparation ability for the tested racemates in comparison with the well-known derivatives of cellulose and amylose. In addition, the dissolvability and swelling of the prepared chitosan bis(halophenylcarbamate)-(isobutyrylamide)s in organic solvents were discussed in particular. The eluent tolerance of the CSP prepared from chitosan bis(3,4-dichlorophenylcarbamate)-(isobutyrylamide), which exhibited relatively more favorable enantioseparation performance among the prepared CSPs, was investigated. It was observed that the tested CSP could be analyzed with 100% ethyl acetate, 100% chloroform and n-hexane/THF (70/30, volume ratio) without a significant loss of recognition and enantioseparation ability. As a consequence, we can safely draw the conclusion that chitosan bis(halophenylcarbamate)-(isobutyrylamide)s prepared from chitosan with a high molecular weight can show good enantioseparation performance as well as satisfactory eluent tolerance.
Effectiveness of N-acetylcysteine in Treating Clinical Symptoms of Substance Abuse and Dependence: A Meta-analysis of Randomized Controlled Trials

Objective Treatment with N-acetylcysteine (NAC) is believed to reduce the clinical symptoms among individuals with substance abuse or dependence. We conducted a meta-analysis of randomized controlled trials to evaluate the effectiveness of NAC in treating substance abuse and dependence. Methods PubMed, EMBASE, ClinicalTrials.gov registry, and the Cochrane Library were searched for trials published before June 2020. Results A total of 16 trials were analyzed. The treatment effectiveness domains assessed in this study were craving and depressive symptoms, withdrawal syndrome, adverse events, and smoking frequency. Standardized mean difference (SMD), weighted mean difference (WMD), and odds ratio (OR) were used for evaluation where appropriate. A significant decrease in craving symptoms was observed in the NAC treatment group compared with the control group (SMD, −0.67; 95% confidence interval [CI], −1.21 to 0.21). When withdrawal and depressive symptoms were considered as a single domain, the NAC treatment group demonstrated a significantly higher overall improvement than the control group (SMD, −0.35; 95% CI, −0.64 to −0.06). No between-group differences in term of the OR of adverse events (OR, 1.18; 95% CI, 0.68 to 2.06) and a non-significant trend toward reduction in smoking frequency was observed in the NAC treatment group compared with the control group (WMD, −3.09; 95% CI, −6.50 to 0.32). Conclusion NAC provides certain noticeable benefits in attenuating substance craving and might help alleviate depressive symptoms and withdrawal syndrome. Precautious measures should be considered when using NAC although no difference in adverse effects was found between NAC treatment and control group.
Warming intensifies soil pathogen negative feedback on a temperate tree

Summary The soil pathogen‐induced Janzen–Connell (JC) effect is considered as a primary mechanism regulating plant biodiversity worldwide. As predicted by the framework of the classic plant disease triangle, severity of plant diseases is often influenced by temperature, yet insufficient understanding of how increasing temperatures affect the JC effect contributes uncertainty in predictions about how global warming affects biodiversity. We conducted a 3‐yr field warming experiment, combining open‐top chambers with pesticide treatment, to test the effect of elevated temperatures on seedling mortality of a temperate tree species, Prunus padus, from a genus with known susceptibility to soil‐borne pathogens. Elevated temperature significantly increased the mortality of P. padus seedlings in the immediate vicinity of parent trees, concurrent with increased relative abundance of pathogenic fungi identified to be virulent to Prunus species. Our study offers experimental evidence suggesting that global warming significantly intensifies the JC effect on a temperate tree species due to increased relative abundance of pathogenic fungi. This work advances our understanding about changes in the JC effect linked to ongoing global warming, which has important implications for predicting tree diversity in a warmer future.
Differences in Biomechanical Loading Magnitude During a Landing Task in Male Athletes with and without Patellar Tendinopathy.

CONTEXT Prior research has not established if overloading or underloading movement profiles are present in symptomatic and asymptomatic athletes with patellar tendon structural abnormality (PTA) compared to healthy athletes. OBJECTIVE The purpose was to compare involved limb landing biomechanics between male athletes with and without patellar tendinopathy. DESIGN Cross-sectional study Setting: Laboratory Patients or Other Participants: 43 males were grouped based on patellar tendon pain & ultrasound imaging of the proximal patellar tendon: symptomatic with PTA (SYM-PTA; n=13; 20±2yrs; 1.8±0.1m; 84±5kg), asymptomatic with PTA (ASYM-PTA; n=15; 21±2yrs; 1.8±0.1m; 82±13kg), and healthy control (CON; n=15; 20±2yrs; 1.8±0.1m; 79±12kg). MAIN OUTCOME MEASURES 3D biomechanics were collected during double-limb jump-landing. Kinematic (knee flexion angle (KF)) and kinetic (vertical ground reaction force (VGRF); internal knee extension moment (KEM); patellar tendon force (FPT)) variables were analyzed as continuous waveforms during the stance phase for the involved limb. Mean values were calculated for each 1% of stance, normalized over 202 data points (0-100%), and plotted with 95% confidence intervals. Statistical significance was defined as a lack of 95% CI overlap for ≥ 6 consecutive data points. RESULTS SYM-PTA had lesser KF than CON throughout the stance phase. ASYM-PTA had lesser KF than CON in the early and late stance phase. SYM-PTA group had lesser KEM and FPT than CON in early stance, as well as ASYM-PTA in mid-stance. CONCLUSIONS Male athletes with SYM-PTA demonstrated a patellar tendon load-avoidance profile compared to ASYM-PTA and CON athletes. ASYM-PTA did not show evidence of overloading compared to CON. Our findings support the need for individualized treatments for athletes with tendinopathy to maximize load-capacity. TRIAL REGISTRY ClinicalTrials.gov (#XXX).
Granulomatosis with polyangiitis in a patient with a thoracic vertebral lesion: a case report

Abstract Granulomatosis with polyangiitis is a systemic, small vessel vasculitis associated with the anti-neutrophil cytoplasmic antibody. We herein report a case of granulomatosis with polyangiitis with paravertebral lesions. A 69-year-old man presented to our hospital with fever, back pain, and myalgia. A computed tomography scan showed multiple lung nodules, while magnetic resonance imaging revealed soft tissue shadows around a thoracic vertebral lesion. A laboratory examination revealed positive myeloperoxidase anti-neutrophil cytoplasmic antibody. He was diagnosed with granulomatosis with polyangiitis. He was treated with oral glucocorticoid and intravenous cyclophosphamide, and the shadows resolved. Physicians should consider granulomatosis with polyangiitis in cases with paravertebral lesions.
Nucleic acid amplification techniques for rapid diagnosis of nontuberculous mycobacteria: A protocol of systematic review and meta-analysis

Background Nontuberculous mycobacteria (NTM) infection is similar to Mycobacterium tuberculosis (MTB) infection. Early clinical identification and differentiation of NTM and MTB infections continues to be a major challenge. Nucleic acid amplification tests (NAATs) have the ability to efficiently and rapidly detect pathogens and are widely used in mycobacterial infections. The objective of this study is to estimate the diagnostic accuracy of NAATs for NTM. Methods We will search candidate studies that assessing the accuracy of NAATs for diagnosis of NTM through PubMed, Embase and the Cochrane Library until May 2021. Studies with full text that meet the inclusion criteria will be included. Following a revised tool for Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2), two researchers will independently evaluate the study quality. The STATA software (version 15.0) will be used to carry out meta-analyses. When heterogeneity is observed, subgroup analyses and meta-regression analyses will be used to explore sources of heterogeneity. Sensitivity analyses will be used to check the robustness of analyses. Conclusion We hope that this study will provide meaningful evidence for the early and rapid diagnosis of NAATs for NTM, which will help to guide the treatment of NTM and improve the prognosis of patients.
Nursing workload associated with the frequency of multidisciplinary rounds: a cross-sectional study

Objective To assess the frequency of multidisciplinary rounds during ICU days, to evaluate the participation of diverse healthcare professionals, to identify the reasons why rounds were not performed on specific days, and whether bed occupancy rate and nurse workload were associated with the conduction of multidisciplinary rounds. Methods We performed a cross-sectional study to assess the frequency of multidisciplinary rounds in four intensive care units in a cancer center. We also collected data on rates of professional participation, reasons for not performing rounds when they did not occur, and daily bed occupancy rates and assessed nurse workload by measuring the Nursing Activity Score. Results Rounds were conducted on 595 (65.8%) of 889 surveyed intensive care unit days. Nurses, physicians, respiratory therapists, pharmacists, and infection control practitioners participated most often. Rounds did not occur due to admission of new patients at the scheduled time (136; 44.7%) and involvement of nurses in activities unrelated to patients’ care (97; 31.9%). In multivariate analysis, higher Nursing Activity Scores were associated with greater odds of conducting multidisciplinary rounds (OR = 1.06; 95%CI 1.04 - 1.10; p < 0.01), whereas bed occupancy rates were not (OR = 0.99; 95%CI 0.97 - 1.00; p = 0.18). Conclusion Multidisciplinary rounds were conducted on less than two-thirds of surveyed intensive care unit days. Many rounds were cancelled due to activities unrelated to patient care. Unexpectedly, increased workload was associated with higher odds of conducting rounds. Workload is a possible trigger to discuss daily goals to improve patient outcomes and to enhance the effectiveness of multidisciplinary teams.
Comparison of Pregnancy Outcomes of Patients Treated With Ondansetron vs Alternative Antiemetic Medications in a Multinational, Population-Based Cohort

Key Points Question What is the association between ondansetron exposure during pregnancy and the risk of adverse fetal outcomes? Findings In this meta-analysis of cohort studies of 456 963 pregnancies in 3 countries, treatment with ondansetron was not significantly associated with increased risk of fetal death, spontaneous abortion, stillbirth, or major congenital malformations compared with other antiemetics. Meaning These findings suggest that ondansetron use during pregnancy is not associated with an increased risk of adverse fetal outcomes compared with the use of other antiemetics.
Low-level expression of necroptosis factors indicates a poor prognosis of the squamous cell carcinoma subtype of non-small-cell lung cancer

Background The programmed cell death pathway necroptosis may synergize with the DNA damage response (DDR) in opposing tumor progression. While our basic mechanistic understanding of the necroptotic cell death advances rapidly, its prognostic implications have not been thoroughly examined in cancers. Methods We included 394 patients with stage I non-small-cell lung cancer (NSCLC) who underwent surgical tumor resection between 1 January 1997 and 31 December 2011 and measured expression levels of nine proteins involved in necroptosis and the DDR in primary samples from 394 patients using tissue microarray. Protein expression evaluated by using an H-score method was dichotomized by the median value. The overall survival as the endpoint was calculated from the time of diagnosis to the time of the last follow-up or death. Results We find that low-level expression of the necroptosis markers RIPK3 and PELI1 is associated with high risk of patient death. High-level expression of the key DDR factor p53 in combination with low-level expression of either RIPK3 or PELI1 increases the risk further. These gene expression effects appear to occur specifically in the squamous cell carcinoma (SCC) subtype of stage I NSCLC, while not observed in the non-SCC subtypes. Conclusions Low-level expression of such necroptosis factors as RIPK3 and PELI1 in combination with high-level expression of the DDR factor p53 can serve as a critical indicator in predicting survival of stage I NSCLC patients with the SCC subtype.