Miracle-dz/UniFAR-FTUs huggingface dataset:
Farnesol remodels the peritoneal cavity immune environment influencing Candida albicans pathogenesis during intra-abdominal infection

ABSTRACT Candida albicans is a lifelong member of the mycobiome causing mucosal candidiasis and life-threatening, systemic, and intra-abdominal disease in immunocompromised and transplant patients. Despite the clinical importance of intra-abdominal candidiasis with mortality rates between 40% and 70%, the contribution of fungal virulence factors and host immune responses to disease has not been extensively studied. Secretion of the quorum-sensing molecule, farnesol, acts as a virulence factor for C. albicans during systemic infection, while inducing local, protective innate immune responses in oral models of infection. Previously, we reported that farnesol recruits macrophages to the peritoneal cavity in mice, suggesting a role for farnesol in innate immune responses. Here, we expand on our initial findings, showing that farnesol profoundly alters the peritoneal cavity microenvironment promoting innate inflammation. Intra-peritoneal injection of farnesol stimulates rapid local death of resident peritoneal cells followed by recruitment of neutrophils and inflammatory macrophages into the peritoneal cavity and peritoneal mesothelium associated with an early increase in chemokines followed by proinflammatory cytokines. These rapid inflammatory responses to farnesol significantly increase morbidity and mortality of mice with intra-abdominal candidiasis associated with increased formation of peritoneal adhesions, despite similar rates of fungal clearance from the peritoneal cavity and retro-peritoneal organs. C. albicans ddp3Δ/ddp3Δ knockout and reconstituted strains recapitulate these findings. This indicates that farnesol may be detrimental to the host during intra-abdominal infections. Importantly, our results highlight a need to understand how C. albicans virulence factors modulate the host immune response within the peritoneum, an exceedingly common site of Candida infection.
Accurate noise-robust classification of Bacillus species from MALDI-TOF MS spectra using a denoising autoencoder

Abstract Bacillus strains are ubiquitous in the environment and are widely used in the microbiological industry as valuable enzyme sources, as well as in agriculture to stimulate plant growth. The Bacillus genus comprises several closely related groups of species. The rapid classification of these remains challenging using existing methods. Techniques based on MALDI-TOF MS data analysis hold significant promise for fast and precise microbial strains classification at both the genus and species levels. In previous work, we proposed a geometric approach to Bacillus strain classification based on mass spectra analysis via the centroid method (CM). One limitation of such methods is the noise in MS spectra. In this study, we used a denoising autoencoder (DAE) to improve bacteria classification accuracy under noisy MS spectra conditions. We employed a denoising autoencoder approach to convert noisy MS spectra into latent variables representing molecular patterns in the original MS data, and the Random Forest method to classify bacterial strains by latent variables. Comparison of the DAE-RF with the CM method using the artificially noisy test samples showed that DAE-RF offers higher noise robustness. Hence, the DAE-RF method could be utilized for noise-robust, fast, and neat classification of Bacillus species according to MALDI-TOF MS data.
Investigation of the role of perceived access to primary care in mediating and moderating racial and ethnic disparities in chronic disease control in the veterans health administration

Abstract Objective To examine the role of patient‐perceived access to primary care in mediating and moderating racial and ethnic disparities in hypertension control and diabetes control among Veterans Health Administration (VA) users. Data Source and Study Setting We performed a secondary analysis of national VA user administrative data for fiscal years 2016–2019. Study Design Our primary exposure was race or ethnicity and primary outcomes were binary indicators of hypertension control (<140/90 mmHg) and diabetes control (HgbA1c < 9%) among patients with known disease. We used the inverse odds‐weighting method to test for mediation and logistic regression with race and ethnicity‐by‐perceived access interaction product terms to test moderation. All models were adjusted for age, sex, socioeconomic status, rurality, education, self‐rated physical and mental health, and comorbidities. Data Collection/Extraction Methods We included VA users with hypertension and diabetes control data from the External Peer Review Program who had contemporaneously completed the Survey of Healthcare Experience of Patients‐Patient‐Centered Medical Home. Hypertension (34,233 patients) and diabetes (23,039 patients) samples were analyzed separately. Principal Findings After adjustment, Black patients had significantly lower rates of hypertension control than White patients (75.5% vs. 78.8%, p < 0.01); both Black (81.8%) and Hispanic (80.4%) patients had significantly lower rates of diabetes control than White patients (85.9%, p < 0.01 for both differences). Perceived access was lower among Black, Multi‐Race and Native Hawaiian and Other Pacific Islanders compared to White patients in both samples. There was no evidence that perceived access mediated or moderated associations between Black race, Hispanic ethnicity, and hypertension or diabetes control. Conclusions We observed disparities in hypertension and diabetes control among minoritized patients. There was no evidence that patients' perception of access to primary care mediated or moderated these disparities. Reducing racial and ethnic disparities within VA in hypertension and diabetes control may require interventions beyond those focused on improving patient access.
Frost periods and frost-free periods in Poland and neighbouringcountries

Abstract The main objective of this article is to analysethe multiannual variability of frost occurrence and thelength of the frost-free period in Poland and neighbouringcountries between 1971 and 2010. A frost day was de-fined as a day onwhich the minimum temperaturewas below0°C and the maximum temperature was above 0°C.On average, between March and November, there were 30frost days in Poland and neighbouring countries, and theirnumber ranged between 12 and 61. In the analysed multiannualperiod, there was a statistically significant tendencyfor the last spring frost to be earlier. Conversely,the first autumn frost occurred increasingly late, althoughthe changes were not statistically significant. All but threestations (Augsburg, Kaliningrad, Olsztyn) recorded an increasein the length of frost-free periods, which was statisticallysignificant in 51% of stations. The pressure conditionconducive to the occurrence of frosts was anticycloniccirculation, as confirmed by the SLP and z500 hPa mapswhich were drawn up, and the Grosswetterlagen (GWL)classification types which were distinguished.
Polyphenols, Antioxidants, and Wound Healing of Lecythis pisonis Seed Coats

Abstract To better use the Lecythis pisonis Cambess. biomass, this study investigates whether Sapucaia seed coats present wound healing properties. We analyzed the antibacterial, antioxidant, and wound healing-promoting potentials, plus cytotoxicity and stimulation of vascular endothelial growth factor-A. The chemical composition was analyzed by positive ion mode electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry. A total of 19 compounds were identified, such as proanthocyanidin A1, procyanidins A1, B2, and C1, epigallocatechin, and kaempferol ( p -coumaroyl) glycoside. Potent antioxidant strength/index was verified for 2,2-diphenyl-1-picrylhydrazyl radical (IC 50 = 0.99 µg/mL) and ferric reducing antioxidant power (IC 50 = 1.09 µg/mL). The extract did not present cytotoxicity and promoted significant cell migration and/or proliferation of fibroblasts (p < 0.05). Vascular endothelial growth factor-A was stimulated dose-dependently at 6 µg/mL (167.13 ± 8.30 pg/mL), 12.5 µg/mL (210.3 ± 14.2 pg/mL), and 25 µg/mL (411.6 ± 29.4 pg/mL). Platelet-derived growth factor (PDGF) (0.002 µg/mL) was stimulated at 215.98 pg/mL. Staphylococcus aureus was susceptible to the extract, with a minimum inhibitory concentration of 31.25 µg/mL. The identified compounds benefit the antioxidant activity, promoting hemostasis for the wound healing process, indicating that this extract has the potential for use in dermatological cosmetics.
Allogenic Umbilical Cord Tissue for Rotator Cuff Injuries

Highly prone to injury, the rotator cuff greatly contributes to the stability and mobility of the shoulder. Clinicians prioritize conservative treatment, resorting to surgery only when necessary, although they are hindered by inherent limitations. Biological therapies, including perinatal tissue, such as umbilical cord (UC) tissue, hold promise for treating rotator cuff injuries (RCIs) in the field of regenerative medicine. This article qualitatively presents the in vitro, preclinical, clinical, and ongoing scientific literature exploring the application of UC tissue and associated mesenchymal stem cells in the context of RCIs. Employing the “Preferred Reporting Items for Systematic Reviews and Meta-analyses” guidelines, a systematic review was conducted. These studies have presented substantial evidence indicating that UC tissue and UC-derived mesenchymal stem cells are safe and potentially efficacious for managing RCIs, though more adequately powered randomized controlled trials are warranted to further establish efficacy and justify clinical use.
CellDialog: A Computational Framework for Ligand-Receptor-Mediated Cell-Cell Communication Analysis

Intercellularcommunication significantly influences tumor progression, metastasis, and therapy resistance. An intercellular communication inference method includes two main procedures: ligand-receptor interaction (LRI) curation and LRI-mediated intercellular communication strength measurement. The construction of a comprehensive, high-confident and well-organized LRI database contributes to intercellular communication inference. Here, we developed a computational framework named CellDialog to reconstruct an intercellular connectivity network based on the combined expression of ligands and receptors involved in sender and receiver cells. CellDialog first captures high-confident LRIs through LRI feature extraction, feature selection, and classification. Furthermore, CellDialog uses a three-point estimation approach to measure the LRI-mediated intercellular communication strength by combining LRI filtering and single-cell RNA sequencing data. A comparison analysis of CellDialog and the other tools was conducted, and it was found that CellDialog can efficiently decode intercellular communications. Additionally, CellDialog offers a heatmap view and network view for intercellular communication visualization. In summary, CellDialog provides a tool that allows researchers to analyze intercellular signal transduction.
Estimating the Uncertainty in a Regional Climate Model Related to Initial and Lateral Boundary Conditions

Abstract There is a growing demand for regional-scale climate predictions and assessments. Quantifying the impacts of uncertainty in initial conditions and lateral boundary forcing data on regional model simulations can potentially add value to the usefulness of regional climate modeling. Results from a regional model depend on the realism of the driving data from either global model outputs or global analyses; therefore, any biases in the driving data will be carried through to the regional model. This study used four popular global analyses and achieved 16 driving datasets by using different interpolation procedures. The spread of the 16 datasets represents a possible range of driving data based on analyses to the regional model. This spread is smaller than typically associated with global climate model realizations of the Arctic climate. Three groups of 16 realizations were conducted using the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale M.
Exosome-delivered circRNA circSYT15 contributes to cisplatin resistance in cervical cancer cells through the miR-503-5p/RSF1 axis

ABSTRACT The development of chemotherapy resistance is a major obstacle for cervical cancer (CC) patients. Exosome-mediated transfer of circular RNAs (circRNAs) was found to have relevance to the CC. This study is designed to explore the role and mechanism of exosomal circRNA synaptotagmin 15 (circSYT15) on cisplatin (DDP) resistance in CC. Cell proliferation ability and apoptosis rate were detected by Cell Counting Kit-8 (CCK-8), 5-ethynyl-2’-deoxyuridine (EdU), colony formation, and flow cytometry assays. CircSYT15, microRNA-503-5p (miR-503-5p), Remodeling spacing factor 1 (RSF1) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Exosomes were analyzed by a transmission electron microscope and nanoparticle tracking analysis. CD63, CD81, TSC101, Bcl-2, Bax, C-caspase 3, and RSF1 protein levels were examined by western blot assay. The binding between miR-503-5p and circSYT15 or RSF1 was predicted by circBank or Starbase and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP). The biological role of exosomal circSYT15 in DDP resistance of CC in vivo. CircSYT15 was upregulated in the DDP-resistant CC cells and exosomes isolated from DDP-resistant CC cells. CircSYT15 knockdown repressed the proliferation and drug resistance of CC and induced apoptosis in CC cells. Exosomes shuttled circSYT15 act as a sponge to affect RSF1 expression, thereby promoting proliferation and drug resistance and repressing apoptosis of sensitive CC cells. Exosomal circSYT15 boost DDP resistance of cervical cancer in vivo. Exosome-mediated transfer of circSYT15 enhanced DDP resistance in CC partly by targeting the miR-503-5p/RSF1 axis, providing a foundation for future clinical applications of CC drug resistance.
Negative emotion reduces the discriminability of reward outcomes in the ventromedial prefrontal cortex

Abstract Reward and emotion are tightly intertwined, so there is a growing interest in mapping their interactions. However, our knowledge of these interactions in the human brain, especially during the consummatory phase of reward is limited. To address this critical gap, we conducted a functional magnetic resonance imaging study to investigate the effects of negative emotion on reward outcome processing. We employed a novel design where emotional valence (negative or neutral) indicated the type of outcome (reward or no-reward) in a choice task. We focused our functional magnetic resonance imaging analysis on the ventro-medial prefrontal cortex (vmPFC), ventral striatum and amygdala, which were frequently implicated in reward outcome processing. In these regions of interest, we performed multi-voxel pattern analysis to specifically probe how negative emotion modulates reward outcome processing. In vmPFC, using decoding analysis, we found evidence consistent with the reduced discriminability of multi-variate activity patterns of reward vs no-reward outcomes when signaled by a negative relative to a neutral image, suggesting an emotional modulation of reward processing along the plausible common value/valence dimension. These findings advance our limited understanding of the basic brain mechanisms underlying the influence of negative emotion on consummatory reward processing, with potential implications for mental disorders, particularly anxiety and depression.
Ex-vivo rectal tissue infection with HIV-1 to assess time to protection following oral preexposure prophylaxis with tenofovir disoproxil/emtricitabine

Objectives: We wished to assess time to protection from HIV-1 infection following oral tenofovir disoproxil and emtricitabine (TDF/FTC) as preexposure prophylaxis (PrEP), using ex-vivo rectal tissue infections and drug concentration measures in blood and rectal tissue. Design/Methods: Participants from the ANRS PREVENIR study (NCT03113123) were offered this sub-study after a 14-day wash-out. We used an ex-vivo model to evaluate rectal tissue HIV-1 susceptibility before and after PrEP, 2 h after two pills or 7 days of a daily pill of TDF/FTC. PrEP efficacy was expressed by the difference (after-before) of 14-day cumulative p24 antigen levels. TFV-DP and FTC-TP levels were measured in rectal tissue and PBMCs and correlated with HIV-1 infection. Results: Twelve and 11 men were analyzed in the 2 h–double dose and 7 days–single dose groups, respectively. Cumulative p24 differences after-before PrEP were -144 pg/ml/mg (IQR[−259;−108]) for the 2 h–double dose group (P = 0.0005) and -179 pg/ml/mg (IQR [−253;−86]) for the 7 days–single dose group (P = 0.001), with no differences between groups (P = 0.93). Rectal TFV-DP was below quantification after a double dose, but FTC-TP levels were similar to levels at 7 days. There was a significant correlation between rectal FTC-TP levels and p24 changes after a double dose (R = −0.84; P = 0.0001). Conclusion: Oral TDF/FTC provided similar protection against HIV-1 infection of rectal tissue 2 h after a double dose or 7 days of a daily dose. At 2 h, this protection seems driven by high FTC-TP concentrations in rectal tissue. This confirms the importance of combining TDF and FTC to achieve early protection.
Behavioral Mechanisms That Mediate Mental and Physical Health Improvements in People With Chronic Pain Who Receive a Digital Health Intervention: Prospective Cohort Pilot Study

Background Preliminary evidence suggests that digital mental health intervention (Wysa for Chronic Pain) can improve mental and physical health in people with chronic musculoskeletal pain and coexisting symptoms of depression or anxiety. However, the behavioral mechanisms through which this intervention acts are not fully understood. Objective The purpose of this study was to identify behavioral mechanisms that may mediate changes in mental and physical health associated with use of Wysa for Chronic Pain during orthopedic management of chronic musculoskeletal pain. We hypothesized that improved behavioral activation, pain acceptance, and sleep quality mediate improvements in self-reported mental and physical health. Methods In this prospective cohort, pilot mediation analysis, adults with chronic (≥3 months) neck or back pain received the Wysa for Chronic Pain digital intervention, which uses a conversational agent and text-based access to human counselors to deliver cognitive behavioral therapy and related therapeutic content. Patient-reported outcomes and proposed mediators were collected at baseline and 1 month. The exposure of interest was participants’ engagement (ie, total interactions) with the digital intervention. Proposed mediators were assessed using the Behavioral Activation for Depression Scale–Short Form, Chronic Pain Acceptance Questionnaire, and Athens Insomnia Scale. Outcomes included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Pain Interference, and Physical Function scores. A mediation analysis was conducted using the Baron and Kenny method, adjusting for age, sex, and baseline mediators and outcome values. P<. 20 was considered significant for this pilot study. Results Among 30 patients (mean age 59, SD 14, years; 21 [70%] female), the mediation effect of behavioral activation on the relationship between increased intervention engagement and improved anxiety symptoms met predefined statistical significance thresholds (indirect effect –0.4, 80% CI –0.7 to –0.1; P=.13, 45% of the total effect). The direction of mediation effect was generally consistent with our hypothesis for all other proposed mediator or outcome relationships, as well. Conclusions In a full-sized randomized controlled trial of patients with chronic musculoskeletal pain, behavioral activation, pain acceptance, and sleep quality may play an important role in mediating the relationship between use of a digital mental health intervention (Wysa for Chronic Pain) and improved mental and physical health. Trial Registration ClinicalTrials.gov NCT05194722; https://clinicaltrials.gov/ct2/show/NCT05194722
In vitro pharmacodynamics of nemonoxacin and other antimicrobial agents against Mycoplasma pneumoniae

ABSTRACT Mycoplasma pneumoniae is the causative agent of respiratory infections in children and adults. Macrolide still plays a significant role in treating infections by M. pneumoniae. However, macrolide-resistant M. pneumoniae (MRMP) was encountered, causing more severe or prolonged disease worldwide from the early 2000s. Nemonoxacin is a newly developed C-8-methoxy non-fluorinated quinolone having broad-spectrum activity against gram-positive, gram-negative, and atypical pathogens in vitro, as well as general safety and well tolerance in vivo. This study aimed to assess the killing kinetics of nemonoxacin and other antimicrobial agents against MRMP and macrolide susceptible M. pneumoniae (MSMP) by static time-kill curves. In addition, the pharmacodynamic analyses of these drugs were determined by the sigmoid E max model. The static time-kill curves indicated that nemonoxacin had good mycoplasmacidal activity against both MSMP and MRMP strains. The pharmacodynamic analysis demonstrated that the mycoplasmacidal effect of nemonoxacin was greater than those of moxifloxacin and levofloxacin based on the K max, displaying a dualism of concentration dependency in low minimum inhibitory concentrations (MICs) and time dependency in high MICs. Therefore, nemonoxacin demonstrated efficacy against M. pneumoniae in vitro and is a potential candidate for clinical studies for assessing its therapeutic effects against M. pneumoniae infections. The killing pattern or PK/PD characteristics of nemonoxacin against M. pneumoniae from in vitro data, animal studies, or clinical studies merit further evaluation for treating infections caused by the organism. IMPORTANCE This study first reported the in vitro effector kinetics of the new non-fluorinated quinolone, nemonoxacin, against macrolide-resistant M. pneumoniae (MRMP) and macrolide susceptible M. pneumoniae (MSMP) strains along with other antimicrobial agents. The time-kill assays and pharmacodynamic analysis showed that nemonoxacin has significant mycoplasmacidal activity against MRMP and MSMP. This study paves the road to establish appropriate dosing protocols of a new antimicrobial drug for children infected with M. pneumoniae. This study first reported the in vitro effector kinetics of the new non-fluorinated quinolone, nemonoxacin, against macrolide-resistant M. pneumoniae (MRMP) and macrolide susceptible M. pneumoniae (MSMP) strains along with other antimicrobial agents. The time-kill assays and pharmacodynamic analysis showed that nemonoxacin has significant mycoplasmacidal activity against MRMP and MSMP. This study paves the road to establish appropriate dosing protocols of a new antimicrobial drug for children infected with M. pneumoniae.