Miracle-dz/UniFAR-FTUs huggingface dataset:
Effectiveness and Safety of Combining Tofacitinib with a Biologic in Patients with Refractory Inflammatory Bowel Diseases

Background: One therapeutic option with limited data among patients with active moderate-to-severe ulcerative colitis (UC) and Crohn's disease (CD) despite biologic monotherapy is using a combination of a biologic with Tofacitinib (TBT). Our aim was to examine the effectiveness and safety of TBT in this subset of patients. Methods: Data of IBD patients at 2 referral centers on TBT were extracted. The primary outcome was clinical response (>50% reduction in symptoms) at week 8 and/or 16 determined by Physician Global Assessment. Secondary outcome was clinical remission (resolution of symptoms), corticosteroid-free clinical response and remission, normalization of CRP and endoscopic/radiographic response and remission. Adverse events (AEs) including any abnormal lipid profile or surgical complications were also assessed. Results: Thirty-five patients (25UC, 10CD) were included. Biologics combined with tofacitinib were vedolizumab (68.6%), ustekinumab (17.1%), and infliximab (14.3%) and the median follow-up duration was 4 months. A majority (57.2%) had failed at least two biologics prior to starting TBT. At weeks 8 and/or 16, 37.1% achieved clinical response with 5.7% in clinical remission. Among the 23 patients with endoscopically/radiographically active disease at baseline, 56.5% had endoscopic/radiographic response and 34.8% achieved remission. Three AEs occurred in 2 (5.7%) patients, with an IR of 20.5 (15.0-47.2)/100PYF. No VTE and herpes zoster was reported. Conclusions: TBT is effective at inducing endoscopic/radiographic response and a modest clinical response in UC and CD patients with active clinical symptoms despite prior biologic monotherapy. No new safety signals were detected beyond those reported with tofacitinib monotherapy.
Association between number of replacements and readmissions following total knee and total hip replacements in New South Wales' public hospitals

Total knee and total hip replacement are common and resource‐intensive procedures. Complications are associated with worse outcomes and can add to the health care costs, particularly if associated with readmission. The aims of this study were to inform quality improvement by reporting on the extent of variation in readmissions across public hospitals and investigating the association between hospital volume and readmissions.
Video Recording and Analysis of Avian Movements and Behavior: Insights from Courtship Case Studies

Abstract Video recordings are useful tools for advancing our understanding of animal movements and behavior. Over the past decades, a burgeoning area of behavioral research has put forward innovative methods to investigate animal movement using video analysis, which includes motion capture and machine learning algorithms. These tools are particularly valuable for the study of elaborate and complex motor behaviors, but can be challenging to use. We focus in particular on elaborate courtship displays, which commonly involve rapid and/or subtle motor patterns. Here, we review currently available tools and provide hands-on guidelines for implementing these techniques in the study of avian model species. First, we suggest a set of possible strategies and solutions for video acquisition based on different model systems, environmental conditions, and time or financial budget. We then outline the available options for video analysis and illustrate how different analytical tools can be chosen to draw inference about animal motor performance. Finally, a detailed case study describes how these guidelines have been implemented to study courtship behavior in golden-collared manakins (Manacus vitellinus).
Asymptomatic bacteriuria: Impact of an antimicrobial stewardship bundle to reduce unnecessary antibiotics in patients without urinary catheters.

PURPOSE The purpose of this study was to evaluate the effect of an antimicrobial stewardship bundle on the management of asymptomatic bacteriuria (ASB). METHODS In this quasi-experimental study, patients were selected by retrospective, consecutive sampling of patients with a positive urine culture report in 3 separate groups: preintervention, postdiagnostic intervention, and posteducation. Patients met the prespecified criteria for non-catheter-associated ASB. The diagnostic intervention involved a new urinalysis/urine culture ordering process in place of urinalysis with reflex to urine culture. Additionally, an educational intervention involved pharmacist-led sessions to educate providers with patient cases and guideline-based recommendations. The primary outcome of this study was the difference in the rate of inappropriate management of ASB, defined as the use of antimicrobial agents intended to treat ASB. Secondary outcomes included length of antimicrobial therapy, length of stay, and change in urine culture orders per 1,000 patient-days. RESULTS A total of 120 patients were included. There was a significant reduction in the inappropriate management of ASB between the preintervention and postdiagnostic intervention groups (P = 0.0349). This was not seen when comparing the postdiagnostic intervention and posteducation groups (P = 0.93). Additionally, there was a significant difference in urinalysis/urine culture ordering between the preintervention and postdiagnostic intervention groups (370 vs 224 urinalysis orders per 1,000 days present, P < 0.0001; 131 vs 54 urine culture orders per 1,000 days present, P < 0.0001). CONCLUSION An antimicrobial stewardship bundle involving a diagnostic stewardship intervention and pharmacist-led education reduced treatment of ASB in patients without urinary catheters.
CX3CR1 Is a Receptor for Human Respiratory Syncytial Virus in Cotton Rats

The knowledge about a virus receptor is useful to better understand the uptake of a virus into a cell and potentially develop antivirals directed against either the receptor molecule on the cell or the receptor-binding protein of the virus. Among a number of potential receptor proteins, human CX3CR1 has been demonstrated to act as a receptor for respiratory syncytial virus (RSV) on human epithelial cells in tissue culture. ABSTRACT Respiratory syncytial virus (RSV) has been reported to use CX3CR1 in vitro as a receptor on cultured primary human airway epithelial cultures. To evaluate CX3CR1 as the receptor for RSV in vivo, we used the cotton rat animal model because of its high permissiveness for RSV infection. Sequencing the cotton rat CX3CR1 gene revealed 91% amino acid similarity to human CX3CR1. Previous work found that RSV binds to CX3CR1 via its attachment glycoprotein (G protein) to infect primary human airway cultures. To determine whether CX3CR1-G protein interaction is necessary for RSV infection, recombinant RSVs containing mutations in the CX3CR1 binding site of the G protein were tested in cotton rats. In contrast to wild-type virus, viral mutants did not grow in the lungs of cotton rats. When RSV was incubated with an antibody blocking the CX3CR1 binding site of G protein and subsequently inoculated intranasally into cotton rats, no virus was found in the lungs 4 days postinfection. In contrast, growth of RSV was not affected after preincubation with heparan sulfate (the receptor for RSV on immortalized cell lines). A reduction in CX3CR1 expression in the cotton rat lung through the use of peptide-conjugated morpholino oligomers led to a 10-fold reduction in RSV titers at day 4 postinfection. In summary, these results indicate that CX3CR1 functions as a receptor for RSV in cotton rats and, in combination with data from human airway epithelial cell cultures, strongly suggest that CX3CR1 is a primary receptor for naturally acquired RSV infection. IMPORTANCE The knowledge about a virus receptor is useful to better understand the uptake of a virus into a cell and potentially develop antivirals directed against either the receptor molecule on the cell or the receptor-binding protein of the virus. Among a number of potential receptor proteins, human CX3CR1 has been demonstrated to act as a receptor for respiratory syncytial virus (RSV) on human epithelial cells in tissue culture. Here, we report that the cotton rat CX3CR1, which is similar to the human molecule, acts as a receptor in vivo. This study strengthens the argument that CX3CR1 is a receptor molecule for RSV.
Exploring group size for statistical analysis of real‐time signalling experiments

Classical pharmacological bioassays generally use observed effects from a concentration series, at a single equilibrium time point to construct a concentration–effect curve, representing one experiment. However, if the full kinetic profile of the effect data for each concentration was evaluated simultaneously, then the analysis would be more powerful. In this work, we explore if more precise parameters can be achieved by using the full kinetic method.
Community-Based Prevalence Estimates of Chlamydia trachomatis and Neisseria gonorrhoeae Infections Among Gay, Bisexual, and Other Men Who Have Sex With Men in Montréal, Canada

This first community-based study among gay, bisexual and other men who have sex with men in Montréal, Canada shows that if testing was limited to the urogenital site, 80% and 94% of Chlamydia trachomatis and Neisseria gonorrhoeae infections, respectively, would have been missed. Supplemental digital content is available in the text. Background Reported cases of Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections are increasing among Canadian men. Estimates of community-based CT/NG prevalence are lacking among gay, bisexual, and other men who have sex with men (GBM). Methods Respondent driven sampling was used to recruit GBM in Montréal, Canada between February 2017 and June 2018. Specimens provided from urogenital, rectal, and pharyngeal sites were analyzed using nucleic acid amplification test to detect CT/NG. Prevalence estimates of CT/NG, overall and by anatomical site were calculated. All estimates are respondent-driven sampling–adjusted. Results Among 1177 GBM, the prevalence of rectal, urogenital, pharyngeal and overall were respectively 2.4%, 0.4%, 0.4%, and 2.8% for CT infections, and 3.1%, 0.4%, 3.5%, and 5.6% for NG infections. If testing had been limited to the urogenital site, 80% and 94% of CT and NG infections, respectively, would have been missed. Conclusions This community-based study among GBM shows that the CT prevalence was about half of that observed for NG. A large part of CT/NG infections involves only the extragenital sites, highlighting the need for systematic multisite screening regardless of symptoms. In the mist of the COVID-19 pandemic and the limited CT/NG screening capacity due to test kits shortage, it might be considered to prioritize rectal and pharyngeal CT/NG testing over urogenital testing in asymptomatic GBM.
Dysfunction in Sertoli cells participates in glucocorticoid‐induced impairment of spermatogenesis

The effect of stress on male fertility is a widespread public health issue, but less is known about the related signaling pathway. To investigate this, we established a hypercortisolism mouse model by supplementing the drinking water with corticosterone for four weeks. In the hypercortisolism mice, the serum corticosterone was much higher than in the control, and serum testosterone was significantly decreased. Moreover, corticosterone treatment induced decrease of sperm counts and increase of teratozoospermia. Increased numbers of multinucleated giant cells and apoptotic germ cells as well as downregulated meiotic markers suggested that corticosterone induced impaired spermatogenesis. Further, upregulation of macrophage‐specific marker antigen F4/80 as well as inflammation‐related genes suggested that corticosterone induced inflammation in the testis. Lactate content was found to be decreased in the testis and Sertoli cells after corticosterone treatment, and lactate metabolism‐related genes were downregulated. In vitro phagocytosis assays showed that the phagocytic activity in corticosterone‐treated Sertoli cells was downregulated and accompanied by decreased mitochondrial membrane potential, while pyruvate dehydrogenase kinase‐4 inhibitor supplementation restored this process. Taken together, our results demonstrated that dysfunctional phagocytosis capacity and lactate metabolism in Sertoli cells participates in corticosterone‐induced impairment of spermatogenesis.
Enhanced monitoring of water quality variation in Nakdong River downstream using multivariate statistical techniques

AbstractThe variation in downstream river water quality was investigated using three multivariate statistical techniques: factor analysis (FA), cluster analysis (CA), and discriminant analysis (DA). Four main factors (FA1, FA2, FA3, and FA4) were defined as changes of “organic matter and nitrogen,” “suspended solid and climate conditions,” “phosphorous and electrical conductivity,” and “discharge,” respectively. The states of each factor were clustered into Low, Normal (Normal_low and Normal_high), and High groups using CA. These groups used to summarize water quality data measured as a series of numbers of contaminants for fast evaluation of water quality and enhanced monitoring capability. To set up a procedure for enhanced monitoring of water quality, Fisher’s linear discriminant functions were deduced to determine the groups in which newly obtained water quality data should be included. To investigate the effectiveness of the proposed tool for enhanced monitoring of river water quality, a case study w.
Rapid and multiplex detection of nosocomial pathogens on a phage‐based magnetoresistive lab‐on‐chip platform

Nosocomial or hospital‐acquired infections (HAIs) have a major impact on mortality worldwide. Enterococcus and Staphylococcus are among the leading causes of HAIs and thus are important pathogens to control mainly due to their increased antibiotic resistance. The gold‐standard diagnostic methods for HAIs are time‐consuming, which hinders timely and adequate treatment. Therefore, the development of fast and accurate diagnostic tools is an urgent demand. In this study, we combined the sensitivity of magnetoresistive (MR) sensors, the portability of a lab‐on‐chip platform, and the specificity of phage receptor binding proteins (RBPs) as probes for the rapid and multiplex detection of Enterococcus and Staphylococcus. For this, bacterial cells were firstly labelled with magnetic nanoparticles (MNPs) functionalized with RBPs and then measured on the MR sensors. The results indicate that the RBP‐MNPS provided a specific individual and simultaneous capture of more than 70% of Enterococcus and Staphylococcus cells. Moreover, high signals from the MR sensors were obtained for these samples, providing the detection of both pathogens at low concentrations (10 CFU/ml) in less than 2 h. Overall, the lab‐on‐chip MR platform herein presented holds great potential to be used as a point‐of‐care for the rapid, sensitive and specific multiplex diagnosis of bacterial infections.
Biochemical characterization of adenosine deaminase (CD26; EC 3.5.4.4) activity in human lymphocyte-rich peripheral blood mononuclear cells

The conversion of adenosine to inosine is catalyzed by adenosine deaminase (ADA) (EC 3.5.4.4), which has two isoforms in humans (ADA1 and ADA2) and belongs to the zinc-dependent hydrolase family. ADA modulates lymphocyte function and differentiation, and regulates inflammatory and immune responses. This study investigated ADA activity in lymphocyte-rich peripheral blood mononuclear cells (PBMCs) in the absence of disease. The viability of lymphocyte-rich PBMCs isolated from humans and kept in 0.9% saline solution at 4-8°C was analyzed over 20 h. The incubation time and biochemical properties of the enzyme, such as its Michaelis-Menten constant (Km) and maximum velocity (Vmax), were characterized through the liberation of ammonia from the adenosine substrate. Additionally, the presence of ADA protein on the lymphocyte surface was determined by flow cytometry using an anti-CD26 monoclonal human antibody, and the PBMCs showed long-term viability after 20 h. The ADA enzymatic activity was linear from 15 to 120 min of incubation, from 2.5 to 12.5 µg of protein, and pH 6.0 to 7.4. The Km and Vmax values were 0.103±0.051 mM and 0.025±0.001 nmol NH3·mg-1·s-1, respectively. Zinc and erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) inhibited enzymatic activity, and substrate preference was given to adenosine over 2′-deoxyadenosine and guanosine. The present study provides the biochemical characterization of ADA in human lymphocyte-rich PBMCs, and indicates the appropriate conditions for enzyme activity quantification.
Ocular Distribution of Papaverine Using Non-aqueous Vehicles

Papaverine, a poorly soluble opium alkaloid, has recently been shown to reduce retinal inflammation due to which it may have therapeutic application in the management of Leber’s hereditary optic neuropathy. In this study, papaverine eyedrops based on medium chain triglycerides were prepared and the effect of diethyl glycol monoethyl ether (DGME) on their ocular distribution was evaluated using an ex vivo porcine eye model. The route of drug penetration was also studied by orienting the eye to expose either only the cornea or the sclera to the formulation. Furthermore, in vivo studies were performed to confirm ocular tolerability and evaluate ocular drug distribution. Our results showed increased papaverine concentrations in the cornea and sclera in the presence of DGME but with a slight reduction in the retina-choroid (RC) drug concentration when administered via the corneal route, suggesting that DGME enhances drug accumulation in the anterior ocular tissues but with little effect on posterior drug delivery. In vivo, the papaverine eyedrop with DGME showed good ocular tolerability with the highest drug concentration being observed in the cornea (1.53 ± 0.28 μg/g of tissue), followed by the conjunctiva (0.74 ± 0.18 μg/g) and sclera (0.25 ± 0.06 μg/g), respectively. However, no drug was detected in the RC, vitreous humor or plasma. Overall, this study highlighted that DGME influences ocular distribution and accumulation of papaverine. Moreover, results suggest that for hydrophobic drugs dissolved in hydrophobic non-aqueous vehicles, transcorneal penetration via the transuveal pathway may be the predominant route for drug penetration to posterior ocular tissues. Graphical abstract Graphical abstract
Nurses' recommendations to the psychoaffective dimensions of patients hospitalized in nephrology.

OBJECTIVES to analyze nurses' recommendations on the psycho-affective dimensions of patients hospitalized in nephrology. METHODS a qualitative, exploratory and descriptive study, carried out by applying a sociodemographic and training questionnaire, reading a clinical case and conducting a semi-structured interview. Fourteen nurses from a reference hospital in nephrology in the Southeast participated. In the technical input of data treatment, thematic content analysis was used. RESULTS the recommendations included the exercise of empathy; monitoring of emotions from the implementation of the nursing consultation; continuous sharing of tensions, anxieties and desires; knowledge of one's emotion; increased availability to listen; effectiveness of the approach in teams and social groups. CONCLUSIONS recognizing patients' psycho-affective dimensions, in the context of nurses' performance, favors the expansion of therapeutic listening spaces, welcoming and interpersonal coexistence in nephrology, essential in the production of comprehensive health care.
Association Between Bitter Taste Receptor Phenotype and Clinical Outcomes Among Patients With COVID-19

Key Points Question What is the association between the bitter taste receptor phenotype and outcomes after infection with SARS-CoV-2? Findings In this cohort study of 1935 adults, 266 tested positive for SARS-CoV-2, and those who experienced low intensity of bitter tastes or no bitter tastes (nontasters) were significantly more likely to test positive for SARS-CoV-2, to be hospitalized, and to be symptomatic for a longer duration. Conversely, those who experienced greater intensity of bitter tastes (supertasters) represented 5.6% of patients infected with SARS-CoV-2, suggesting enhanced innate immune protection. Meaning This study suggests that bitter taste receptor allelic variants are associated with innate immune fitness toward SARS-CoV-2 and can be used to correlate with clinical course and prognosis of COVID-19.
Donor kidney lithiasis and back-table endoscopy: a successful combination

Abstract Introduction Urolithiasis in renal allografts is relatively rare with an incidence of 0.17–4.40%. It is nonetheless an important issue, as there is a risk of obstruction, sepsis and even loss of the renal allograft. The management of stones in renal allografts remains challenging because of the anatomy, the renal denervation and the use of immunosuppressive medication. Case presentation This report discusses the ex-vivo treatment of asymptomatic nephrolithiasis in a living donor kidney allograft. A CT abdomen revealed a lower pole stone (5.9 × 5.5 × 5.0 mm; 920 HU) in the right kidney of the potential donor. After multidisciplinary discussion, it was decided to procure the right kidney despite the presence of a documented nephrolithiasis. After discussion with both donor and recipient, an ex-vivo flexible ureterorenoscopy for stone removal on the back table just before implantation of the allograft was planned. The stone was found in the lower pole covered by a thin film of the urothelium. The thin film of urothelium was opened with a laser and the stone fragments were retrieved with a basket. CT after one month showed no residual stones in the transplanted kidney. Conclusion Back-table endoscopy in a renal allograft is a feasible technique and should be discussed as an option in case of urolithiasis in a kidney that is considered for transplantation. Furthermore, the appropriate treatment of donor kidney lithiasis is another, although rare, method to expand the living donor renal allograft pool.
Spectral analysis of physiological brain pulsations affecting the BOLD signal

Physiological pulsations have been shown to affect the global blood oxygen level dependent (BOLD) signal in human brain. While these pulsations have previously been regarded as noise, recent studies show their potential as biomarkers of brain pathology. We used the extended 5 Hz spectral range of magnetic resonance encephalography (MREG) data to investigate spatial and frequency distributions of physiological BOLD signal sources. Amplitude spectra of the global image signals revealed cardiorespiratory envelope modulation (CREM) peaks, in addition to the previously known very low frequency (VLF) and cardiorespiratory pulsations. We then proceeded to extend the amplitude of low frequency fluctuations (ALFF) method to each of these pulsations. The respiratory pulsations were spatially dominating over most brain structures. The VLF pulsations overcame the respiratory pulsations in frontal and parietal gray matter, whereas cardiac and CREM pulsations had this effect in central cerebrospinal fluid (CSF) spaces and major blood vessels. A quasi‐periodic pattern (QPP) analysis showed that the CREM pulsations propagated as waves, with a spatiotemporal pattern differing from that of respiratory pulsations, indicating them to be distinct intracranial physiological phenomenon. In conclusion, the respiration has a dominant effect on the global BOLD signal and directly modulates cardiovascular brain pulsations.