Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of a low FODMAP diet on the colonic microbiome in irritable bowel syndrome: a systematic review with meta-analysis

ABSTRACT Background A low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet is increasingly used to manage symptoms in irritable bowel syndrome (IBS). Although this approach may alter the colonic microbiome, the nature of these changes has not been comprehensively synthesized. Objectives The aim of this study was to conduct a systematic review with meta-analysis of randomized controlled trials examining the impact of a low FODMAP diet on the composition and function of the microbiome in patients with IBS. Methods A systematic search was conducted for randomized controlled trials evaluating the effects of a low FODMAP diet on the colonic microbiome in patients with IBS in MEDLINE, EMBASE, CENTRAL, and Web of Science from inception to April 2022. Outcomes included diversity of the microbiome, specific bacterial abundances, fecal SCFA concentration, and fecal pH. For fecal SCFA concentrations and pH, meta-analyses were performed via a random-effects model. Results Nine trials involving 403 patients were included. There were no clear effects of the low FODMAP diet on diversity of the microbiome. A low FODMAP diet consistently led to lower abundance of Bifidobacteria, but there were no clear effects on diversity of the microbiome or abundances of other specific taxa. There were no differences in total fecal SCFA concentration between the low FODMAP diet and control diets (standardized mean difference: −0.25; 95% CI: −0.63, 0.13; P = 0.20), nor were there differences for fecal concentrations of specific SCFAs or fecal pH. Conclusions In patients with IBS, the effects of a low FODMAP diet on the colonic microbiome appear to be specific to Bifidobacteria with no consistent impacts on other microbiome metrics, including diversity, fecal SCFA concentrations, and fecal pH. Further, adequately powered trials are needed to confirm these findings. This review was registered at https://www.crd. york.ac. uk/prospero/ as CRD42020192243.
Blocking cell cycle progression through CDK4/6 protects against chronic kidney disease

Acute and chronic kidney injuries induce increased cell cycle progression in renal tubules. While increased cell cycle progression promotes repair after acute injury, the role of ongoing tubular cell cycle progression in chronic kidney disease is unknown. Two weeks after initiation of chronic kidney disease, we blocked cell cycle progression at G1/S phase by using an FDA-approved, selective inhibitor of CDK4/6. Blocking CDK4/6 improved renal function and reduced tubular injury and fibrosis in 2 murine models of chronic kidney disease. However, selective deletion of cyclin D1, which complexes with CDK4/6 to promote cell cycle progression, paradoxically increased tubular injury. Expression quantitative trait loci (eQTLs) for CCND1 (cyclin D1) and the CDK4/6 inhibitor CDKN2B were associated with eGFR in genome-wide association studies. Consistent with the preclinical studies, reduced expression of CDKN2B correlated with lower eGFR values, and higher levels of CCND1 correlated with higher eGFR values. CDK4/6 inhibition promoted tubular cell survival, in part, through a STAT3/IL-1β pathway and was dependent upon on its effects on the cell cycle. Our data challenge the paradigm that tubular cell cycle progression is beneficial in the context of chronic kidney injury. Unlike the reparative role of cell cycle progression following acute kidney injury, these data suggest that blocking cell cycle progression by inhibiting CDK4/6, but not cyclin D1, protects against chronic kidney injury.
Expression Profile and Localization of SARS-CoV-2 Nonstructural Replicase Proteins in Infected Cells

The intracellular localization of SARS-CoV-2 replicase nonstructural proteins (nsp) during infection has not been fully elucidated. In this study, we systematically analyzed the expression and subcellular localization of 11 distinct viral nsp and dsRNA over time in SARS-CoV-2-infected cells by using individual antibody against these replicase proteins. ABSTRACT Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is responsible for the COVID-19 pandemic that has caused unprecedented loss of life and economic trouble all over the world, though the mechanism of its replication remains poorly understood. In this study, antibodies were generated and used to systematically determine the expression profile and subcellular distribution of 11 SARS-CoV-2 nonstructural replicase proteins (nsp1, nsp2, nsp3, nsp5, nsp7, nsp8, nsp9, nsp10, nsp13, nsp14, and nsp15) by Western blot and immunofluorescence assay. Nsp3, nsp5, and nsp8 were detected in perinuclear foci at different time points, with diffusion and stronger fluorescence observed over time. In particular, colocalization of nsp8 and nsp13 with different replicase proteins suggested viral protein-protein interaction, which may be key to understanding their functions and potential molecular mechanisms. Viral intermediate dsRNA was detected in perinuclear foci as early as 2-h postinfection, indicating the initiation of virus replication. With the passage of time, these perinuclear dsRNA foci became larger and brighter, and nearly all colocalized with N protein, consistent with viral growth over time. Thus, the development of these anti-nsp antibodies provides basic tools for the further study of replication and diagnosis of SARS-CoV-2. IMPORTANCE The intracellular localization of SARS-CoV-2 replicase nonstructural proteins (nsp) during infection has not been fully elucidated. In this study, we systematically analyzed the expression and subcellular localization of 11 distinct viral nsp and dsRNA over time in SARS-CoV-2-infected cells by using individual antibody against these replicase proteins. The data indicated that nsp gene expression is highly regulated in space and time, which could be useful to understand the function of viral replicases and future development of diagnostics and potential antiviral strategies against SARS-CoV-2.
Bacteraemia and infective endocarditis with Streptococcus bovis-Streptococcus equinus-complex: a retrospective cohort study

Abstract Background Streptococcus bovis/equinus complex (SBSEC) comprise several species and subspecies and is a common cause of infective endocarditis (IE). S. gallolyticus subsp. gallolyticus (Sg gallolyticus) accounts for a majority of SBSEC IE, but the risk of IE for other subspecies is largely unknown. We aimed to investigate the clinical presentation of bacteraemia, and proportion of patients with IE in bacteraemia with the most common subspecies. Methods A retrospective cohort study of SBSEC-bacteraemia identified in clinical laboratory databases, in Skåne Region, Sweden, 2003–2018. Bacteraemia with Sg gallolyticus, S. gallolyticus subsp. pasteurianus (Sg pasteurianus), S. lutetiensis and S. infantarius subsp. infantarius (Si infantarius) were included. Subspecies was identified by whole genome sequencing. Medical charts were reviewed according to a predetermined protocol, IE was defined by the criteria from European Society of Cardiology. Results In total, 210 episodes of SBSEC-bacteraemia were included. Definite IE was identified in 28/210 (13%) episodes. Of these, 7/28 (25%) were prosthetic valve-IE, 1/28 (4%) related to a cardiovascular implantable electronic device and 10/28 (36%) required heart valve surgery. The proportions of IE among different subspecies were: Sg gallolyticus 17/52 (33%), Si infantarius 5/31 (16%), Sg pasteurianus 4/83 (5%) and S. lutetiensis 2/44 (5%) (p < 0.001). Sg pasteurianus and S. lutetiensis were more often associated with intra-abdominal- and polymicrobial infection. Conclusion The proportion of IE in SBSEC-bacteraemia varies substantially depending on subspecies. Echocardiography should always be considered in bacteraemia with Sg gallolyticus and Si infantarius, and can sometimes be omitted in bacteraemia with Sg pasteurianus and S. lutetiensis.
Limitations of Molecular and Antigen Test Performance for SARS-CoV-2 in Symptomatic and Asymptomatic COVID-19 Contacts

COVID-19 has brought unprecedented attention to the crucial role of diagnostics in pandemic control. We compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test performance by sample type and modality in close contacts of SARS-CoV-2 cases. ABSTRACT COVID-19 has brought unprecedented attention to the crucial role of diagnostics in pandemic control. We compared severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) test performance by sample type and modality in close contacts of SARS-CoV-2 cases. Close contacts of SARS-CoV-2-positive individuals were enrolled after informed consent. Clinician-collected nasopharyngeal (NP) swabs in viral transport media (VTM) were tested with a routine clinical reference nucleic acid test (NAT) and PerkinElmer real-time reverse transcription-PCR (RT-PCR) assay; positive samples were tested for infectivity using a VeroE6TMPRSS2 cell culture model. Self-collected passive drool was also tested using the PerkinElmer RT-PCR assay. For the first 4 months of study, midturbinate swabs were tested using the BD Veritor rapid antigen test. Between 17 November 2020 and 1 October 2021, 235 close contacts of SARS-CoV-2 cases were recruited, including 95 with symptoms (82% symptomatic for ≤5 days) and 140 asymptomatic individuals. Reference NATs were positive for 53 (22.6%) participants; 24/50 (48%) were culture positive. PerkinElmer testing of NP and saliva samples identified an additional 28 (11.9%) SARS-CoV-2 cases who tested negative by reference NAT. Antigen tests performed for 99 close contacts showed 83% positive percent agreement (PPA) with reference NAT among early symptomatic persons, but 18% PPA in others; antigen tests in 8 of 11 (72.7%) culture-positive participants were positive. Contacts of SARS-CoV-2 cases may be falsely negative early after contact, but more sensitive platforms may identify these cases. Repeat or serial SARS-CoV-2 testing with both antigen and molecular assays may be warranted for individuals with high pretest probability for infection.
Solving Games in Parallel with Linear-Time Perfect Hash Functions

In this paper, we propose an efficient method of solving oneand two-player combinatorial games by mapping each state to a unique bit in memory. In order to avoid collisions, a concise portfolio of perfect hash functions is provided. Such perfect hash functions then address tables that serve as a compressed representation of the search space and support the execution of exhaustive search algorithms like breadth-first search and retrograde analysis. Perfect hashing computes the rank of a state, while the inverse operation unrank reconstructs the state given its rank. Efficient algorithms are derived, studied in detail and generalized to a larger variety of games. We study rank and unrank functions for permutation games with distinguishable pieces, for selection games with indistinguishable pieces, and for general reachability sets. The running time for ranking and unranking in all three cases is linear in the size of the state vector. To overcome space and time limitations in solving previously unsolved games like Frogsand-Toads and Fox-and-Geese, we utilize parallel computing power in form of multiple cores as available on modern central processing units (CPUs) and graphics processing units (GPUs). We obtain an almost linear speedup with the number of CPU cores. Due to its much larger number of cores, even better absolute speed-up are achieved on the GPU.
Hypomagnesemia, Hypocalcemia, and Tubulointerstitial Nephropathy Caused by Claudin-16 Autoantibodies

Significant Statement Chronic hypomagnesemia is commonly due to diarrhea, alcoholism, and drugs; more rarely, genetic defects in the effectors of renal magnesium reabsorption are responsible. The authors report on an adult patient with acquired severe hypomagnesemia, hypocalcemia, and tubulointerstitial nephropathy, with rapidly progressing kidney injury. In in vivo and in vitro studies, they found evidence of a causal link between the patient’s condition and autoantibodies against claudin-16, a transmembrane paracellular protein involved in renal magnesium absorption. The patient was subsequently diagnosed with a renal carcinoma that expressed a high level of claudin-16 mRNA. Pathogenic claudin-16 autoantibodies represent a novel autoimmune cause of specific renal tubular transport disturbances and tubulointerstitial nephropathy. Screening for autoantibodies targeting claudin-16 and potentially other renal magnesium transporters or channels may be warranted in patients with acquired unexplained hypomagnesemia. Visual Abstract Background Chronic hypomagnesemia is commonly due to diarrhea, alcoholism, and drugs. More rarely, it is caused by genetic defects in the effectors of renal magnesium reabsorption. Methods In an adult patient with acquired severe hypomagnesemia, hypocalcemia, tubulointerstitial nephropathy, and rapidly progressing kidney injury, similarities between the patient’s presentation and features of genetic disorders of renal magnesium transport prompted us to investigate whether the patient had an acquired autoimmune cause of renal magnesium wasting. To determine if the patient’s condition might be explained by autoantibodies directed against claudin-16 or claudin-19, transmembrane paracellular proteins involved in renal magnesium absorption, we conducted experiments with claudin knockout mice and transfected mouse kidney cells expressing human claudin-16 or claudin-19. We also examined effects on renal magnesium handling in rats given intravenous injections of IgG purified from sera from the patient or controls. Results Experiments with the knockout mice and in vitro transfected cells demonstrated that hypomagnesemia in the patient was causally linked to autoantibodies directed against claudin-16, which controls paracellular magnesium reabsorption in the thick ascending limb of Henle’s loop. Intravenous injection of IgG purified from the patient’s serum induced a marked urinary waste of magnesium in rats. Immunosuppressive treatment combining plasma exchange and rituximab was associated with improvement in the patient’s GFR, but hypomagnesemia persisted. The patient was subsequently diagnosed with a renal carcinoma that expressed a high level of claudin-16 mRNA. Conclusions Pathogenic claudin-16 autoantibodies represent a novel autoimmune cause of specific renal tubular transport disturbances and tubulointerstitial nephropathy. Screening for autoantibodies targeting claudin-16, and potentially other magnesium transporters or channels in the kidney, may be warranted in patients with acquired unexplained hypomagnesemia.
Effects of cell wall polysaccharides on the bioaccessibility of carotenoids, polyphenols, and minerals: an overview

Abstract Carotenoids, polyphenols, and minerals (CPMs) are representative bioactive compounds and micronutrients in plant-based foods, showing many potentially positive bioactivities. Bioaccessibility is a prerequisite for bioactivities of CPMs. Cell wall polysaccharides (CWPs) are major structural components of plant cell wall, and they have been proven to affect the bioaccessibility of CPMs in different ways. This review summarizes recent literatures about the effects of CWPs on the bioaccessibility of CPMs and discusses the potential mechanisms. Based on the current findings, CWPs can inhibit the bioaccessibility of CPMs in gastrointestinal tract. The effects of CWPs on the bioaccessibility of polyphenols and minerals mainly attributes to bind between them, while CWPs affect the bioaccessibility of carotenoids by changing the digestive environment. Further, this review overviews the factors (environmental conditions, CWPs properties and CPMs characteristics) affecting the interactions between CWPs and CWPs. This review may help to better design healthy and nutritious foods precisely.
Neuronal Correlates of Hyperalgesia and Somatic Signs of Heroin Withdrawal in Male and Female Mice

Abstract Opioid withdrawal involves the manifestation of motivational and somatic symptoms. However, the brain structures that are involved in the expression of different opioid withdrawal signs remain unclear. We induced opioid dependence by repeatedly injecting escalating heroin doses in male and female C57BL/6J mice. We assessed hyperalgesia during spontaneous heroin withdrawal and somatic signs of withdrawal that was precipitated by the preferential μ-opioid receptor antagonist naloxone. Heroin-treated mice exhibited significantly higher hyperalgesia and somatic signs than saline-treated mice. Following behavioral assessment, we measured regional changes in brain activity by automated the counting of c-Fos expression (a marker of cellular activity). Using Principal Component Analysis, we determined the association between behavior (hyperalgesia and somatic signs of withdrawal) and c-Fos expression in different brain regions. Hyperalgesia was associated with c-Fos expression in the lateral hypothalamus, central nucleus of the amygdala, ventral tegmental area, parabrachial nucleus, dorsal raphe (DR), and locus coeruleus (LC). Somatic withdrawal was associated with c-Fos expression in the paraventricular nucleus of the thalamus, lateral habenula, DR, and LC. Thus, hyperalgesia and somatic withdrawal signs were each associated with c-Fos expression in unique sets of brain areas. The expression of c-Fos in the DR and LC was associated with both hyperalgesia and somatic withdrawal. Understanding common neurobiological mechanisms of acute and protracted opioid withdrawal may help identify new targets for treating this salient aspect of opioid use disorder.
Clinicopathological Features and Mortality in Patients With Kaposi Sarcoma and HIV: A Retrospective Analysis of a Thirty-Year Study From a Peruvian Oncologic Center

PURPOSE Kaposi's sarcoma (KS) is a multifocal angioproliferative disease. In Peru, the implementation of the highly active antiretroviral treatment (HAART) program was in 2005, the model for treating patients with HIV-positive KS shifted to a potential cure. In this study, we aim to compare clinicopathological characteristics and prognostic factors associated with outcomes in patients with HIV-positive KS. METHODS We developed a retrospective cohort study that includes patients with HIV/AIDS and KS seen in the Instituto Nacional de Enfermedades Neoplasicas between 1987 and 2017. Patients were divided into two groups according to the implementation of HAART in our country: the non-HAART group and those treated with HAART after 2005. Multivariate analysis for overall survival (OS) was performed with the Cox proportional hazard regression model. RESULTS There was a greater visceral compromise and more extensive oral cavity involvement in the non-HAART group (60% 31.7%, P < .01). Regarding the immune status, there was a significant difference from the CD4 count at 1-year follow-up (73 v 335, P = .01). The CD4/CD8 rate were significant different before QT (0.23 v 0.13, P = .01) and at 1-year follow-up (0.12 v 0.32, P = .03.). The estimated 5-year OS rate was significantly lower (P = .0001) for the non-HAART group (41.7%; 95% CI, 25.9 to 56.9) compared with the HAART group (79.3%; 95% CI, 66.8 to 87.5). In the multivariate model for OS, full-HAART regimen and previous diagnosis of HIV/AIDS (P < .01) were significantly associated with longer survival. CONCLUSION Clinical and demographic characteristics of our patients are compatible with the literature, but we report a higher rate of gastrointestinal involvement. Furthermore, our findings provide evidence for the importance of HAART and its ability to reduce KS-related mortality.
Investigation of the effects of antimicrobial and anti‐biofilm peptide IDR1018 and chitosan nanoparticles on ciprofloxacin‐resistant Escherichia coli

Peptide IDR1018 and chitosan nanoparticles (CNs) showed antimicrobial and anti‐biofilm activity against bacteria. In this study, the antimicrobial effects of peptide IDR1018 and CNs were evaluated on 50 clinical isolates of uropathogenic Escherichia coli (UPEC) resistant to ciprofloxacin. Ion gelation method was applied for CNs synthesis. Scanning electron microscope (SEM) and dynamic light scattering (DLS) were utilized to evaluate the nanoparticles. Antimicrobial and synergistic activity of peptide IDR1018 and CNs with ciprofloxacin were evaluated by microtiter broth dilution method. The checkerboard test was used to investigate the antimicrobial effects of IDR1018 and CNS in combination with ciprofloxacin. Anti‐biofilm effect of ciprofloxacin, peptide IDR1018, and CNs was evaluated using crystal violet method. Fourteen (28%), 21 (42%), and 15 (30%) of clinical isolates produced strong, moderate, and weak biofilm, respectively. The CNs were spherical and uniform under electron microscopy with an average diameter of 246 nm. The minimum inhibitory concentration (MIC) values were 16–128, 20–40, and 375–750 (µg/ml) for ciprofloxacin, peptide IDR1018, and CNs, respectively. Fractional inhibitory concentration (FIC) analysis indicated a synergistic effect of ciprofloxacin in combination with peptide IDR1018, but in combination with CNs, this antibiotic showed an additive effect. Our results revealed that peptide IDR1018 and CNs have antimicrobial properties on UPEC isolates. Biofilm inhibition and biofilm eradication of clinical isolate were shown by peptide IDR1018 and CNs in a concentration‐dependent manner. The antimicrobial agents alone and in combination decreased the number of viable bacteria in the biofilms. Therefore, these components seem to be a treating approach against biofilm‐forming UPEC isolates.
Factors associated with potential drug–drug interactions in psychiatric inpatients

Objective The aim of this study was to investigate the prevalence and severity of potential drug–drug interactions (pDDIs) in hospitalised patients with major psychiatric disorders and to identify factors associated with their occurrence. Methods The research was designed as an observational, cross-sectional study conducted at the Clinic for Mental Disorders (CMD) ‘Dr. Laza Lazarevic’, Belgrade, Serbia. Medscape, Epocrates and Lexicomp bases were used to detect potential drug interactions among inpatients. Multivariate regression analysis was used to reveal risk and protective factors associated with the number of pDDIs. Results The study included 511 patients, average age 44.63±11.81 years. The average number of pDDIs per patient ranged from 5.9±4.7 (Medscape) to 8.2±5.4 (Epocrates) and 8.5±5.1 (Lexicomp). The following risk factors were identified by all three interaction checkers used: C-reactive protein, number of pharmacological subgroups, number of prescribed drugs, antibiotics, antacids, vitamins, number of associated comorbidities, route, form and dose of the drug. Conclusions When making clinical decisions to reduce drug problems, including DDIs, one should consult several interaction databases, which should be reviewed by a multidisciplinary team consisting of an experienced clinical pharmacist, physician, nurse, and so on.