Miracle-dz/UniFAR-FTUs huggingface dataset:
Microbiome Profiles of Ligature-Induced Periodontitis in Nonhuman Primates across the Life Span

This investigation compared the microbiomes colonizing teeth during the initiation, progression, and resolution of periodontitis in nonhuman primates (Macaca mulatta) at different ages. Subgingival plaque samples were collected at baseline; 0.5, 1, and 3 months following ligature-induced periodontitis; and following naturally occurring disease resolution at 5 months. ABSTRACT This investigation compared the microbiomes colonizing teeth during the initiation, progression, and resolution of periodontitis in nonhuman primates (Macaca mulatta) at different ages. Subgingival plaque samples were collected at baseline; 0.5, 1, and 3 months following ligature-induced periodontitis; and following naturally occurring disease resolution at 5 months. Samples were analyzed using 16S amplicon sequencing to identify bacterial profiles across age groups: young (<3 years of age), adolescent (3 to 7 years), adult (12 to 15 years), and aged (17 to 23 years). α-Diversity of the microbiomes was greater in the adult/aged samples than in the young/adolescent samples. β-Diversity of the samples demonstrated clear age group differences, albeit individual variation in microbiomes between animals within the age categories was noted. Phylum distributions differed between the young/adolescent animals and the adult/aged animals at each of the time points, showing an enrichment of the phyla Spirochetes, Fusobacteria, and Bacteroidetes associated with periodontitis. Major differences in the top 50 operational taxonomic units (OTUs) were noted in the young and adolescent microbiomes during initiation and progression postligation compared to the adult and aged animals. The proportions of a large number of species in the top 50 OTUs were lower at baseline and in resolved disease microbiomes in the young samples, while profiles in adolescent animals were more consistent with the disease microbiomes. Microbiome profiles for resolution for adults and aged animals appeared more resilient and generally maintained a pattern similar to that of disease. Use of the model can expand our understanding of the crucial interactions of the oral microbiome and host responses in periodontitis.
Differential network enrichment analysis reveals novel lipid pathways in chronic kidney disease

MOTIVATION Functional enrichment testing methods can reduce data comprising hundreds of altered biomolecules to smaller sets of altered biological 'concepts' that help generate testable hypotheses. This study leveraged differential network enrichment analysis methodology to identify and validate lipid subnetworks that potentially differentiate chronic kidney disease (CKD) by severity or progression. RESULTS We built a partial correlation interaction network, identified highly connected network components, applied network-based gene-set analysis to identify differentially enriched subnetworks, and compared the subnetworks in patients with early-stage versus late-stage CKD. We identified two subnetworks 'triacylglycerols' and 'cardiolipins-phosphatidylethanolamines (CL-PE)' characterized by lower connectivity, and a higher abundance of longer polyunsaturated triacylglycerols in patients with severe CKD (stage ≥4) from the Clinical Phenotyping Resource and Biobank Core. These finding were replicated in an independent cohort, the Chronic Renal Insufficiency Cohort. Using an innovative method for elucidating biological alterations in lipid networks, we demonstrated alterations in triacylglycerols and cardiolipins-phosphatidylethanolamines that precede the clinical outcome of end-stage kidney disease by several years. AVAILABILITY AND IMPLEMENTATION A complete list of NetGSA results in HTML format can be found at http://metscape.ncibi. org/netgsa/12345-022118/cric_cprobe/022118/results_cric_cprobe/main.html. The DNEA is freely available at https://github.com/wiggie/DNEA. Java wrapper leveraging the cytoscape.js framework is available at http://js.cytoscape. org. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Epigenetic Changes Induced by Bacteroides fragilis Toxin

Enterotoxigenic Bacteroides fragilis (ETBF) is a Gram-negative, obligate anaerobe member of the gut microbial community in up to 40% of healthy individuals. This bacterium is found more frequently in people with colorectal cancer (CRC) and causes tumor formation in the distal colon of multiple intestinal neoplasia (Apcmin/+) mice; tumor formation is dependent on ETBF-secreted Bacteroides fragilis toxin (BFT). ABSTRACT Enterotoxigenic Bacteroides fragilis (ETBF) is a Gram-negative, obligate anaerobe member of the gut microbial community in up to 40% of healthy individuals. This bacterium is found more frequently in people with colorectal cancer (CRC) and causes tumor formation in the distal colon of multiple intestinal neoplasia (Apcmin/+) mice; tumor formation is dependent on ETBF-secreted Bacteroides fragilis toxin (BFT). Because of the extensive data connecting alterations in the epigenome with tumor formation, initial experiments attempting to connect BFT-induced tumor formation with methylation in colon epithelial cells (CECs) have been performed, but the effect of BFT on other epigenetic processes, such as chromatin structure, remains unexplored. Here, the changes in gene expression (transcriptome sequencing [RNA-seq]) and chromatin accessibility (assay for transposase-accessible chromatin using sequencing) induced by treatment of HT29/C1 cells with BFT for 24 and 48 h were examined. Our data show that several genes are differentially expressed after BFT treatment and that these changes relate to the interaction between bacteria and CECs. Further, sites of increased chromatin accessibility are associated with the location of enhancers in CECs and the binding sites of transcription factors in the AP-1/ATF family; they are also enriched for common differentially methylated regions (DMRs) in CRC. These data provide insight into the mechanisms by which BFT induces tumor formation and lay the groundwork for future in vivo studies to explore the impact of BFT on nuclear structure and function.
A systems biology view of wood formation in Eucalyptus grandis trees submitted to different potassium and water regimes.

Wood production in fast-growing Eucalyptus grandis trees is highly dependent on both potassium (K) fertilization and water availability but the molecular processes underlying wood formation in response to the combined effects of these two limiting factors remain unknown. E. grandis trees were submitted to four combinations of K-fertilization and water supply. Weighted gene co-expression network analysis and MixOmics-based co-regulation networks were used to integrate xylem transcriptome, metabolome and complex wood traits. Functional characterization of a candidate gene was performed in transgenic E. grandis hairy roots. This integrated network-based approach enabled us to identify meaningful biological processes and regulators impacted by K-fertilization and/or water limitation. It revealed that modules of co-regulated genes and metabolites strongly correlated to wood complex traits are in the heart of a complex trade-off between biomass production and stress responses. Nested in these modules, potential new cell-wall regulators were identified, as further confirmed by the functional characterization of EgMYB137. These findings provide new insights into the regulatory mechanisms of wood formation under stressful conditions, pointing out both known and new regulators co-opted by K-fertilization and/or water limitation that may potentially promote adaptive wood traits.
Use of tube cystostomy in the surgical management of obstructive urolithiasis in a Bactrian camel.

CASE DESCRIPTION A 6-year-old castrated male Bactrian camel was evaluated because of a 14hour history of oliguria and stranguria that progressed to anuria. CLINICAL FINDINGS Perineal urethral pulsations and intermittent tail flagging with no accompanying urination were observed. Ultrasonography of the urethra revealed multiple hyperechoic foci with shadowing artifact indicative of calculi present in the penile urethra distal to the sigmoid flexure. Rectal palpation revealed a pulsating hard urethra and intact distended urinary bladder. Further clinical examination was not possible because of challenges associated with handling the camel. TREATMENT AND OUTCOME Urethral catheterization through a perineal urethral incision failed to achieve urinary bladder decompression. Tube cystostomy was performed to prevent bladder rupture. Urethrocystography performed 3 days after surgery revealed a urethral rupture at the level of the prepuce. Five weeks after surgery, the camel could urinate a steady stream via the urethrotomy site. Seven weeks after surgery, the cystostomy tube was removed, and the urethrotomy site was modified to provide a permanent urethral opening via perineal urethrostomy. During 6 years of subsequent periodic follow-up by telephone, the owner reported that the camel continued to do well and urinate through the revised opening. CLINICAL RELEVANCE To the authors' knowledge, this is the first detailed description of a tube cystostomy in an adult camel with obstructive urolithiasis that includes information on the patient's long-term outcome. This technique was a viable option in the surgical management of obstructive urolithiasis in this camel and may be useful for other large camelids as well.
An initial randomized controlled trial of behavioral activation for treatment of concurrent crystal methamphetamine dependence and sexual risk for HIV acquisition among men who have sex with men

ABSTRACT Men who have sex with men (MSM) continue to be the largest risk group for HIV infections in the U.S., where crystal methamphetamine abuse heightens risk for HIV infection through greater engagement in condomless anal sex (CAS). Existing treatments lack attention to replacement activities or the role of depressed mood. Behavioral activation (BA) is an evidence-based approach for depression that involves identifying and participating in pleasurable, goal-directed activities. We hypothesize, for MSM abusing crystal methamphetamine, re-learning how to engage in non-drug-using aspects of life would facilitate their ability to benefit from sexual risk reduction (SRR) counseling. Project IMPACT was a pilot randomized-controlled-trial. Forty-six MSM at sexual risk of acquiring HIV who met DSM-IV criteria for crystal methamphetamine dependence were enrolled. Of those MSM, 41 were randomized: 21 were assigned to the intervention, two sessions of SRR, ten sessions of BA with SRR, and one session of relapse prevention; 20 participants were assigned to a control condition (two sessions of SRR). At the acute post-intervention visit, intervention participants reported an average of 3.2 CAS acts with men who were HIV-infected or whose status they did not know, compared to 4.5 among control participants (β = −0.36; 95% CI: −0.69, −0.02; p = 0.035). At the 6-month post-intervention visit, intervention participants reported 1.1 CAS acts with men who were HIV-infected or whose status they did not know compared to 2.8 among control participants (β = −0.95; 95% CI: −1.44, −0.46; p < 0.0001). Similarly, intervention participants reported 1.0 CAS acts under the influence of crystal methamphetamine with men who were HIV-infected or whose status they did not know compared to 2.5 among control participants (β = −0.87; 95% CI: −1.38, −0.36; p = 0.0005). Lastly, intervention participants reported more continuous days abstaining from crystal methamphetamine compared to control (50.1 vs. 39.0, respectively) (β = 0.25; 95% CI: 0.16, 0.34; p < 0.0001). Findings are encouraging, provide evidence of feasibility and acceptability, and demonstrate initial efficacy for reducing sexual risk for HIV and crystal methamphetamine use.
Identifying pediatric lung disease: A comparison of forced oscillation technique outcomes

Increasing evidence suggests the forced oscillation technique (FOT) has the capacity to provide non‐invasive monitoring and diagnosis of respiratory disease in young children. However, which FOT outcomes provide the most pertinent clinical information is currently unknown. The aim of this study was to determine which FOT outcomes were most sensitive for differentiating between health and specific childhood respiratory disease.
Social Support for Active Substance Users: A Content Analysis of r/Drugs

ABSTRACT Substance abuse remains an important and dangerous societal issue. In this study, we build on previous literature that identified online social support communities that encouraged unhealthy behaviors, by investigating a platform that provides social support related to engaging in illicit drug use. Three days’ worth of posts, amounting to almost 400 pages of written data, was collected and analyzed to identify what types of support were being requested and provided by users. The analysis identified 19 total topics for support, with 14 of those topics relating to action-facilitating support, and five of them relating to nurturant support. The results show that the website is primarily used to discuss topics like drug effects and drug dosages. This raises questions as to whether these discussions increase safety by allowing users to dose accurately, or whether they give users a false sense of security related to their continued substance use.
Endoscopic posterior cricoid reduction: A surgical method to improve posterior glottic diastasis

Describe the preoperative evaluation of patients with glottic diastasis who are candidates for endoscopic posterior cricoid reduction (EPCR) and their perioperative and postoperative surgical and voice outcomes, and validate the aerodynamic benefit of EPCR using computation fluid dynamics (CFD)‐based modeling from computed tomography (CT) scans.
Step-to-step variations in human running reveal how humans run without falling

Humans can run without falling down, usually despite uneven terrain or occasional pushes. Even without such external perturbations, intrinsic sources like sensorimotor noise perturb the running motion incessantly, making each step variable. Here, using simple and generalizable models, we show that even such small step-to-step variability contains considerable information about strategies used to run stably. Deviations in the center of mass motion predict the corrective strategies during the next stance, well in advance of foot touchdown. Horizontal motion is stabilized by total leg impulse modulations, whereas the vertical motion is stabilized by differentially modulating the impulse within stance. We implement these human-derived control strategies on a simple computational biped, showing that it runs stably for hundreds of steps despite incessant noise-like perturbations or larger discrete perturbations. This running controller derived from natural variability echoes behaviors observed in previous animal and robot studies.
Adaptation to HIF1α Deletion in Hypoxic Cancer Cells by Upregulation of GLUT14 and Creatine Metabolism

Hypoxia-inducible factor 1α is a key regulator of the hypoxia response in normal and cancer tissues. It is well recognized to regulate glycolysis and is a target for therapy. However, how tumor cells adapt to grow in the absence of HIF1α is poorly understood and an important concept to understand for developing targeted therapies is the flexibility of the metabolic response to hypoxia via alternative pathways. We analyzed pathways that allow cells to survive hypoxic stress in the absence of HIF1α, using the HCT116 colon cancer cell line with deleted HIF1α versus control. Spheroids were used to provide a 3D model of metabolic gradients. We conducted a metabolomic, transcriptomic, and proteomic analysis and integrated the results. These showed surprisingly that in three-dimensional growth, a key regulatory step of glycolysis is Aldolase A rather than phosphofructokinase. Furthermore, glucose uptake could be maintained in hypoxia through upregulation of GLUT14, not previously recognized in this role. Finally, there was a marked adaptation and change of phosphocreatine energy pathways, which made the cells susceptible to inhibition of creatine metabolism in hypoxic conditions. Overall, our studies show a complex adaptation to hypoxia that can bypass HIF1α, but it is targetable and it provides new insight into the key metabolic pathways involved in cancer growth. Implications: Under hypoxia and HIF1 blockade, cancer cells adapt their energy metabolism via upregulation of the GLUT14 glucose transporter and creatine metabolism providing new avenues for drug targeting.
The Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods

This clinical report updates and replaces a 2008 clinical report from the American Academy of Pediatrics, which addressed the roles of maternal and early infant diet on the prevention of atopic disease, including atopic dermatitis, asthma, and food allergy. As with the previous report, the available data still limit the ability to draw firm conclusions about various aspects of atopy prevention through early dietary interventions. Current evidence does not support a role for maternal dietary restrictions during pregnancy or lactation. Although there is evidence that exclusive breastfeeding for 3 to 4 months decreases the incidence of eczema in the first 2 years of life, there are no short- or long-term advantages for exclusive breastfeeding beyond 3 to 4 months for prevention of atopic disease. The evidence now suggests that any duration of breastfeeding ≥3 to 4 months is protective against wheezing in the first 2 years of life, and some evidence suggests that longer duration of any breastfeeding protects against asthma even after 5 years of age. No conclusions can be made about the role of breastfeeding in either preventing or delaying the onset of specific food allergies. There is a lack of evidence that partially or extensively hydrolyzed formula prevents atopic disease. There is no evidence that delaying the introduction of allergenic foods, including peanuts, eggs, and fish, beyond 4 to 6 months prevents atopic disease. There is now evidence that early introduction of peanuts may prevent peanut allergy.
A new phenanthropyran and a new biphenanthrene from the rhizomes of Dioscorea septemloba and their antioxidant activities

Abstract A new phenanthropyran, dioscorone B (1), and a new phenanthrene (2), together with seven known compounds (3–9), were isolated from the 75% ethanol extract of Dioscorea septemloba rhizomes. The chemical structures of these compounds were elucidated by comprehensive spectroscopic methods including NMR, HRESIMS, IR, and UV spectra. Compounds 1–5 were first isolated from genus Dioscorea. The proton and carbon chemical shifts of compounds 1–9 were unambiguously assigned based on the 1D-NMR and 2D-NMR data. Compounds 1–5 and 8–9 were first tested for their antioxidant activities. Compounds 1 and 2 showed excellent activities with IC50 values of 0.07 ± 0.10 μM and 0.13 ± 0.09 μM, respectively. Graphical Abstract
The Divergent Roles of Dietary Saturated and Monounsaturated Fatty Acids on Nerve Function in Murine Models of Obesity

Neuropathy is the most common complication of prediabetes and diabetes and presents as distal-to-proximal loss of peripheral nerve function in the lower extremities. Neuropathy progression and disease severity in prediabetes and diabetes correlates with dyslipidemia in man and murine models of disease. Dyslipidemia is characterized by elevated levels of circulating saturated fatty acids (SFAs) that associate with the progression of neuropathy. Increased intake of monounsaturated fatty acid (MUFA)-rich diets confers metabolic health benefits; however, the impact of fatty acid saturation in neuropathy is unknown. This study examines the differential effect of SFAs and MUFAs on the development of neuropathy and the molecular mechanisms underlying the progression of the complication. Male mice Mus musculus fed a high-fat diet rich in SFAs developed robust peripheral neuropathy. This neuropathy was completely reversed by switching the mice from the SFA-rich high-fat diet to a MUFA-rich high-fat diet; nerve conduction velocities and intraepidermal nerve fiber density were restored. A MUFA oleate also prevented the impairment of mitochondrial transport and protected mitochondrial membrane potential in cultured sensory neurons treated with mixtures of oleate and the SFA palmitate. Moreover, oleate also preserved intracellular ATP levels, prevented apoptosis induced by palmitate treatment, and promoted lipid droplet formation in sensory neurons, suggesting that lipid droplets protect sensory neurons from lipotoxicity. Together, these results suggest that MUFAs reverse the progression of neuropathy by protecting mitochondrial function and transport through the formation of intracellular lipid droplets in sensory neurons. SIGNIFICANCE STATEMENT There is a global epidemic of prediabetes and diabetes, disorders that represent a continuum of metabolic disturbances in lipid and glucose metabolism. In the United States, 80 million individuals have prediabetes and 30 million have diabetes. Neuropathy is the most common complication of both disorders, carries a high morbidity, and, despite its prevalence, has no treatments. We report that dietary intervention with monounsaturated fatty acids reverses the progression of neuropathy and restores nerve function in high-fat diet-fed murine models of peripheral neuropathy. Furthermore, the addition of the monounsaturated fatty acid oleate to sensory neurons cultured under diabetic conditions shows that oleate prevents impairment of mitochondrial transport and mitochondrial dysfunction through a mechanism involving formation of axonal lipid droplets.
Signs consistent with syringobulbia may be detected in dogs undergoing MRI.

Syringobulbia is a pathologic condition characterized by one or more fluid-filled cavities within the brainstem. This retrospective case series describes observations in eight dogs with syringobulbia diagnosed during MRI. All dogs were adult, small-breed dogs with concurrent syringomyelia and neurologic deficits localized to sites rostral to the spinal cord, which cannot be explained by syringomyelia (eg, six dogs had vestibular signs). On MRI, the fluid-filled cavities had signal intensity characteristics like cerebrospinal fluid, were in the medulla oblongata, and were solitary in each dog. Initially, the shape of the cavity was a slit in five dogs and bulbous in two dogs. Magnetic resonance imaging was repeated in five dogs (6-55 months of age). One dog had progression of syringobulbia from slit-like to bulbous, and four dogs had unchanged slit-like syringobulbia. One dog developed slit-like syringobulbia after cranioplasty. A variety of medical and surgical treatments were performed with improvement of some but not all clinical signs. One dog died following surgery due to cardiopulmonary failure and the other seven dogs were alive at least 1 year after the initial diagnosis, which was the least time of follow-up. One surviving dog developed a unilateral hypoglossal nerve deficit 2 months after the initial diagnosis and megaesophagus 14 months later. In conclusion, detecting a fluid-filled cavity in the medulla oblongata consistent with syringobulbia is possible in dogs undergoing MRI. The cavity is likely acquired, slit-like or bulbous, progressive, or static, and might be associated with breed size and neurologic signs localized to the medulla oblongata.