Miracle-dz/UniFAR-FTUs huggingface dataset:
Lung Epithelial Signaling Mediates Early Vaccine-Induced CD4+ T Cell Activation and Mycobacterium tuberculosis Control

Tuberculosis is a leading cause of death due to single infectious agent accounting 1.4 million deaths each year. The only licensed vaccine, BCG, is not effective due to variable efficacy. ABSTRACT Tuberculosis (TB) is one of the leading causes of death due to a single infectious agent. The development of a TB vaccine that induces durable and effective immunity to Mycobacterium tuberculosis (Mtb) infection is urgently needed. Early and superior Mtb control can be induced in M. bovis Bacillus Calmette-Guérin (BCG)-vaccinated hosts when the innate immune response is targeted to generate effective vaccine-induced immunity. In the present study, we show that innate activation of DCs is critical for mucosal localization of clonally activated vaccine-induced CD4+ T cells in the lung and superior early Mtb control. In addition, our study reveals that Th1/Th17 cytokine axis play an important role in superior vaccine-induced immunity. Our studies also show that activation of the nuclear factor kappa-light-chain enhancer of activated B cell (NF-κβ) pathway in lung epithelial cells is critical for the mucosal localization of activated vaccine-induced CD4+ T cells for rapid Mtb control. Thus, our study provides novel insights into the immune mechanisms that can overcome TB vaccine bottlenecks and provide early rapid Mtb control. IMPORTANCE Tuberculosis is a leading cause of death due to single infectious agent accounting 1.4 million deaths each year. The only licensed vaccine, BCG, is not effective due to variable efficacy. In our study, we determined the early immune events necessary for achieving complete protection in a BCG-vaccinated host. Our study reveals that innate activation of DCs can mediate superior and early Mtb control in BCG-vaccinated mice through lung epithelial cell signaling and localization of clonal activated, Mtb antigen-specific, cytokine-producing CD4+ T cells within the lung parenchyma and airways. Thus, our study provides novel insights into the immune mechanisms that can overcome TB vaccine bottlenecks and provide early rapid Mtb control.
Finite-Time Stability of Nonlinear Impulsive Systems With Applications to Neural Networks

This article studies the problem of finite-time stability (FTS) and finite-time contractive stability (FTCS) for nonlinear impulsive systems, where the possibility of time delay in impulses is fully considered. Some sufficient conditions for FTS/FTCS are constructed in the framework of Lyapunov function methods. A relationship between impulsive frequency and the time delay existing in impulses is established to reveal FTS/FTCS performance. As an application, we apply the theoretical results to finite-time state estimation of neural networks, including time-varying neural networks and switched neural networks. Finally, two illustrated examples are given to show the effectiveness and distinctiveness of the proposed delay-dependent impulsive schemes.
PARP-1 inhibition attenuates the inflammatory response in the cartilage of a rat model of osteoarthritis

Aims Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model. Methods The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA). Results PARP-1 expression level significantly increased in the cartilage of the established OA rat model. sh-PARP-1 treatment suppressed PARP-1 levels, decreased the Δ Force (the difference between the weight on ipsilateral limb and contralateral limb) and the knee joint width, inhibited cartilage matrix catabolic enzymes, and ameliorated OA cartilage degradation and attenuated inflammatory response. Conclusion PARP-1 inhibition attenuates OA cartilage inflammatory response in the OA rat model. Cite this article: Bone Joint Res 2021;10(7):401–410.
Investigation of the association between human fascia lata thickness and its neighboring tissues' morphology and function using B‐mode ultrasonography

The fascia lata is a membrane tissue which envelopes all thigh muscles and connects with the subcutaneous adipose tissues through loose connective tissues. It is presumable that the morphology of the fascia lata is strongly affected by the unique properties of underlying thigh muscles and subcutaneous adipose tissues. We aimed to investigate the relationships between characteristics of the fascia lata and adjoining adipose tissues and underlying muscles. Twenty healthy people were recruited (25 ± 3 years, 167.1 ± 8.5 cm, 62.5 ± 13.2 kg). The thickness of the skeletal muscles (rectus femoris, vastus lateralis, biceps femoris, and semitendinosus), and their overlying fascia lata and subcutaneous adipose tissues were measured by B‐mode ultrasonography. Isometric knee extension and flexion torque during maximal voluntary contraction were also tested. The fascia lata thickness demonstrated site‐dependent differences (vastus lateralis: 0.91 ± 0.20 mm > rectus femoris, biceps femoris, and semitendinosus: 0.56–0.69 mm, p < 0.01). Furthermore, there were large individual variations in the fascia lata thickness even in the same region of the thigh. The fascia lata showed positive simple correlations with height (rectus femoris: r = 0.39 p = 0.01, semitendinosus: r = 0.37 p < 0.05), body mass (rectus femoris: r = 0.59, p < 0.01, vastus lateralis: r = 0.47, p < 0.01, semitendinosus: r = 0.55, p < 0.01), corresponding muscle thickness (rectus femoris: r = 0.39, p < 0.05, semitendinosus: r = 0.74, p < 0.01) and knee extension (rectus femoris: r = 0.52, p < 0.01, vastus lateralis: r = 0.40, p < 0.01) and flexion (semitendinosus: r = 0.41, p < 0.01) torques. After adjusting for the influence of height and/or body mass, the fascia lata thickness showed a partial correlation only with the skeletal muscle thickness at the semitendinosus (r = 0.61, p < 0.01). The present study revealed that the fascia lata has site‐specific differences of the thickness, which positively correlates with the underlying muscle thickness and corresponding joint torque. Furthermore, the fascia lata over the semitendinosus is associated with the underlying muscle characteristics independent of the physical constitution. It is assumed that the fascia lata has the plasticity and changes its thickness, which likely corresponds to the morphology of the neighboring tissues and underlying muscle function.
Section II Additional modifications for ABCD BIDS pipeline 1 ) PreFreesurfer changes

Section II Additional modifications for ABCD BIDS pipeline 1) PreFreesurfer changes The HCP PreFreeSurfer stage takes a set of anatomical T1-weighted and T2-weighted raw images, with an optional field map, and computes several features: a linear transform to the standard template (each), a brain-ROI mask, relevant image restoration, and a nonlinear registration to the standard atlas using FSL FNIRT. As this is the first stage, any small errors in extracting these features can cause unexpected problems in downstream preprocessing stages. We modified the pipeline to permit an optional T2w image, allowing legacy datasets to be processed. The added benefit of an optional T2 may allow for greater data inclusion when a high quality T1 but poor quality T2 were acquired, which may affect the MRI processing and resultant imaging data quality. We also perform the nonlinear registration to the standard atlas in 3) PostFreeSurfer, which increases the effectiveness of the registration.
Fish primary embryonic pluripotent cells assemble into retinal tissue mirroring in vivo early eye development

Organoids derived from pluripotent stem cells promise the solution to current challenges in basic and biomedical research. Mammalian organoids are however limited by long developmental time, variable success, and lack of direct comparison to an in vivo reference. To overcome these limitations and address species-specific cellular organization, we derived organoids from rapidly developing teleosts. We demonstrate how primary embryonic pluripotent cells from medaka and zebrafish efficiently assemble into anterior neural structures, particularly retina. Within 4 days, blastula-stage cell aggregates reproducibly execute key steps of eye development: retinal specification, morphogenesis, and differentiation. The number of aggregated cells and genetic factors crucially impacted upon the concomitant morphological changes that were intriguingly reflecting the in vivo situation. High efficiency and rapid development of fish-derived organoids in combination with advanced genome editing techniques immediately allow addressing aspects of development and disease, and systematic probing of impact of the physical environment on morphogenesis and differentiation.
Crosstalk of physiological pH and chemical pKa under the umbrella of physiologically based pharmacokinetic modeling of drug absorption, distribution, metabolism, excretion, and toxicity

ABSTRACT Introduction: Physiological pH and chemical pKa are two sides of the same coin in defining the ionization of a drug in the human body. The Henderson-Hasselbalch equation and pH-partition hypothesis form the theoretical base to define the impact of pH-pKa crosstalk on drug ionization and thence its absorption, distribution, metabolism, excretion, and toxicity (ADMET). Areas covered: Human physiological pH is not constant, but a diverse, dynamic state regulated by various biological mechanisms, while the chemical pKa is generally a constant defining the acidic dissociation of the drug at various environmental pH. Works on pH-pKa crosstalk are scattered in the literature, despite its significant contributions to drug pharmacokinetics, pharmacodynamics, safety, and toxicity. In particular, its impacts on drug ADMET have not been effectively linked to the physiologically based pharmacokinetic (PBPK) modeling and simulation, a powerful tool increasingly used in model-informed drug development (MIDD). Expert opinion: Lacking a full consideration of the interactions of physiological pH and chemical pKa in a PBPK model limits scientists’ capability in mechanistically describing the drug ADMET. This mini-review compiled literature knowledge on pH-pKa crosstalk and its impacts on drug ADMET, from the viewpoint of PBPK modeling, to pave the way to a systematic incorporation of pH-pKa crosstalk into PBPK modeling and simulation.
Development and Validation of a Risk Prediction Model for Second Primary Lung Cancer

Abstract Background With advancing therapeutics, lung cancer (LC) survivors are rapidly increasing in number. Although mounting evidence suggests LC survivors have high risk of second primary lung cancer (SPLC), there is no validated prediction model available for clinical use to identify high-risk LC survivors for SPLC. Methods Using data from 6325 ever-smokers in the Multiethnic Cohort (MEC) study diagnosed with initial primary lung cancer (IPLC) in 1993-2017, we developed a prediction model for 10-year SPLC risk after IPLC diagnosis using cause-specific Cox regression. We evaluated the model’s clinical utility using decision curve analysis and externally validated it using 2 population-based data—Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and National Lung Screening Trial (NLST)—that included 2963 and 2844 IPLC (101 and 93 SPLC cases), respectively. Results Over 14 063 person-years, 145 (2.3%) ever-smoking IPLC patients developed SPLC in MEC. Our prediction model demonstrated a high predictive accuracy (Brier score = 2.9, 95% confidence interval [CI] = 2.4 to 3.3) and discrimination (area under the receiver operating characteristics [AUC] = 81.9%, 95% CI = 78.2% to 85.5%) based on bootstrap validation in MEC. Stratification by the estimated risk quartiles showed that the observed SPLC incidence was statistically significantly higher in the 4th vs 1st quartile (9.5% vs 0.2%; P < .001). Decision curve analysis indicated that in a wide range of 10-year risk thresholds from 1% to 20%, the model yielded a larger net-benefit vs hypothetical all-screening or no-screening scenarios. External validation using PLCO and NLST showed an AUC of 78.8% (95% CI = 74.6% to 82.9%) and 72.7% (95% CI = 67.7% to 77.7%), respectively. Conclusions We developed and validated a SPLC prediction model based on large population-based cohorts. The proposed prediction model can help identify high-risk LC patients for SPLC and can be incorporated into clinical decision making for SPLC surveillance and screening.
Mistranslation Reduces Mutation Load in Evolving Proteins through Negative Epistasis with DNA Mutations

Abstract Translational errors during protein synthesis cause phenotypic mutations that are several orders of magnitude more frequent than DNA mutations. Such phenotypic mutations may affect adaptive evolution through their interactions with DNA mutations. To study how mistranslation may affect the adaptive evolution of evolving proteins, we evolved populations of green fluorescent protein (GFP) in either high-mistranslation or low-mistranslation Escherichia coli hosts. In both hosts, we first evolved GFP under purifying selection for the ancestral phenotype green fluorescence, and then under directional selection toward the new phenotype yellow fluorescence. High-mistranslation populations evolved modestly higher yellow fluorescence during each generation of evolution than low-mistranslation populations. We demonstrate by high-throughput sequencing that elevated mistranslation reduced the accumulation of deleterious DNA mutations under both purifying and directional selection. It did so by amplifying the fitness effects of deleterious DNA mutations through negative epistasis with phenotypic mutations. In contrast, mistranslation did not affect the incidence of beneficial mutations. Our findings show that phenotypic mutations interact epistatically with DNA mutations. By reducing a population’s mutation load, mistranslation can affect an important determinant of evolvability.
Campylobacter in waterborne epidemics in Finland

The sources for drinking water in Finland are surface water, groundwater or artificially recharged groundwater. There are approximately 1400 groundwater plants in Finland that are microbiologically at a high risk level because in most cases they do not use any disinfection treatment. Campylobacter jejuni has caused waterborne epidemics in several countries. Since the middle of the 1980s, C. jejuni has been identified as the causative agent in several waterborne outbreaks in Finland. Between 1998 and 2001, C. jejuni or C. upsaliensis caused seven reported waterborne epidemics. In these epidemics approximately 4000 people acquired the illness. Most of the outbreaks occurred in July, August , September or October. In four of them source water and net water samples were analysed for total coliforms or fecal coliforms, E. coli and campylobacters. We showed that large volumes of water samples in studies of indicator organisms (up to 5000 ml) and campylobacters (4000–20,000 ml) increased the possibility to identify faecal contamination and to detect the causative agent from suspected sources.
Effectiveness of cervicothoracic and thoracic manual physical therapy in managing upper quarter disorders – a systematic review

ABSTRACT Study Design Systematic review. Background Physical therapists often use cervicothoracic and thoracic manual techniques to treat musculoskeletal disorders of the upper quarter ,however, the overall effectiveness of this approach remains to be elucidated. Objective This systematic review explored studies that examined the short- and long-term effectiveness of manual physical therapy directed at the cervicothoracic and thoracic region in the management of upper quarter musculoskeletal conditions. Methods The electronic databases MEDLINE, AMED, CINAHL, and Embase were searched from their inception through 30 October 2020. Eligible clinical trials included those where human subjects treated with cervicothoracic and/or thoracic manual procedures were compared with a control group or other interventions. The methodological quality of individual studies was assessed using the PEDro scale. Results The initial search returned 950 individual articles. After the screening of titles and abstracts, full texts were reviewed by two authors, with 14 articles determined to be eligible for inclusion. PEDro scores ranged from 66 to 10 (out of a maximum score of 10). In the immediate to 52-week follow-up period, studies provided limited evidence that cervicothoracic and thoracic manual physical therapy may reduce pain and improve function when compared to control/sham or other treatments. Conclusions Evidence provides some support for the short-termeffectiveness of cervicothoracic and thoracic manual physical therapy in reducing pain and improving function in people experiencing upper quarter musculoskeletal disorders. Evidence is lacking for long-term effectiveness as only two studies explored outcomes beyond 26 weeks and this was for patient-perceived improvement. Prospero ID CRD42020219456
Association Between Iatrogenic Delivery for Suspected Fetal Growth Restriction and Childhood School Outcomes.

Importance Timely delivery of infants suspected of having fetal growth restriction (FGR) is a balance between preventing stillbirth and minimizing prematurity, particularly because many infants with suspected FGR have normal growth. Objective To explore the association between iatrogenic delivery for suspected FGR and childhood school outcomes. Design, Setting, and Participants A retrospective whole-population cohort study linking perinatal data from births 32 weeks' or more gestation between January 1, 2003, to December 31, 2013, to developmental and educational test scores at preparatory school, and at school grades 3, 5, and 7 in Victoria, Australia. Follow-up was concluded in 2019. Exposures Suspicion or nonsuspicion of FGR, presence or absence of iatrogenic delivery (defined as early induction of labor or cesarean delivery prior to labor) for suspected FGR, and presence or absence of small for gestational age (SGA). Main Outcomes and Measures The coprimary outcomes were being in the bottom 10th percentile on 2 or more of 5 developmental domains at school entry and being below the national minimum standard on 2 or more of 5 educational domains in grades 3, 5, or 7. Results In the birth population of 705 937 infants, the mean gestation at birth was 39.1 (SD, 1.5) weeks and the mean birth weight was 3426 (SD, 517) grams. The birth population linked to 181 902 children with developmental results and 425 717 children with educational results. Compared with infants with severe SGA (birth weight <3rd percentile) not suspected of having FGR, infants with severe SGA delivered for suspected FGR were born earlier (mean gestation, 37.9 weeks vs 39.4 weeks). They also had a significantly increased risk of poor developmental outcome at school entry (16.2% vs 12.7%; absolute difference, 3.5% [95% CI, 0.5%-6.5%]); adjusted odds ratio [aOR], 1.36 [95% CI, 1.07-1.74]) and poor educational outcomes in grades 3, 5, and 7 (for example, in grade 7: 13.4% vs 10.5%; absolute difference, 2.9% [95% CI, 0.4%-5.5%]); aOR, 1.33 [95% CI, 1.04-1.70]). There was no significant difference between infants with normal growth (birth weight ≥10th percentile) delivered for suspected FGR and those not suspected of having FGR in developmental outcome (8.6% vs 8.1%; absolute difference, 0.5% [95% CI, -1.1% to 2.0%]); aOR, 1.17 [95% CI, 0.95-1.45]) or educational outcome in grade 3, 5 or 7, despite being born earlier (mean gestation, 38.0 weeks vs 39.1 weeks). Conclusions and Relevance In this exploratory study conducted in Victoria, Australia, iatrogenic delivery of infants with severe SGA due to suspected FGR was associated with poorer school outcomes compared with infants with severe SGA not suspected of having FGR. Iatrogenic delivery of infants with normal growth due to suspected FGR was not associated with poorer school outcomes compared with infants with normal growth not suspected of having FGR.
Atherogenic Dyslipidemia on Admission Is Associated With Poorer Outcome in People With and Without Diabetes Hospitalized for COVID-19

OBJECTIVE Identifying metabolic factors associated with critical disease can help to improve management of patients hospitalized for coronavirus disease 2019 (COVID-19). High triglycerides and low HDL levels characterize the atherogenic dyslipidemia closely related to insulin resistance and diabetes. We examined associations of atherogenic dyslipidemia detected on admission with outcome of COVID-19 during hospitalization. RESEARCH DESIGN AND METHODS We retrospectively analyzed clinical reports of 118 consecutive patients hospitalized for COVID-19 in Rome, Italy, between March and May 2020. Clinical characteristics, inflammation markers, and glucose and lipid metabolism parameters at admission were collected. Critical disease was defined as in-hospital death or need for endotracheal intubation. Associations were tested using logistic regression analysis. RESULTS Patients with critical COVID-19 (n = 43) were significantly older than those with noncritical disease (n = 75) and presented higher levels of fasting glucose, triglycerides, C-reactive protein, interleukin-6, procalcitonin, and d-dimer (P < 0.01 for all), whereas HDL levels were lower (P = 0.003). Atherogenic dyslipidemia was more frequent in patients with critical COVID-19 (46 vs. 24%, P = 0.011), as well as diabetes (37 vs. 19%, P = 0.026), and significantly associated with death or intubation (odds ratio 2.53 [95% CI 1.16–6.32], P = 0.018). Triglycerides were significantly associated with selected inflammatory biomarkers (P < 0.05 for all) and poorer outcome of COVID-19 during hospitalization in both the overall population and the subgroup with atherogenic dyslipidemia. CONCLUSIONS Atherogenic dyslipidemia detected on admission can be associated with critical in-hospital course of COVID-19. Further investigations are needed to elucidate the hypothetical role of insulin resistance and related lipid abnormalities in severe acute respiratory syndrome coronavirus 2 pathogenesis. Assessment of lipid profile should be encouraged in patients hospitalized for COVID-19.
Catalyst Properties and Catalytic Performance of Char from Biomass Gasification

Gasification provides a mechanism to convert solids, such as biomass, coal, or waste, into fuels that can be easily integrated into current infrastructure. This paper discusses the use of residual char from a biomass gasifier as a catalyst for tar decomposition and presents an investigation of the catalytic properties of the char. Poplar wood was gasified in a fluidized bed reactor at temperatures ranging from 550 to 920 °C in reaction environments of 90% steam/10% N2 and 90% N2/10% CO2. The properties of the char recovered from the process were analyzed, and the catalytic performance for hydrocarbon cracking reactions was tested. Brunauer–Emmett–Teller (BET) measurements showed that the surface area of the char was higher than conventional catalyst carriers. The surface area, which ranged from 429 to 687 m2 g–1, increased with temperature and reaction time. The catalytic activity of the char was demonstrated through testing the catalytic decomposition of methane and propane to produce H2 and solid carbon.