Miracle-dz/UniFAR-FTUs huggingface dataset:
Predictors of functional capacity as measured by the Glittre activities of daily living test in women with rheumatoid arthritis

Although pulmonary involvement is the most common extra-articular manifestation of rheumatoid arthritis (RA), traditional pulmonary function tests (PFTs) do not show a good correlation with the field tests usually performed in these patients. In recent decades, measurement of ventilation distribution heterogeneity through the nitrogen single-breath washout (N2SBW) test and evaluation of functional capacity during exercise using the Glittre activities of daily living test (GA-T) have been increasingly used. Therefore, the objective of this study was to evaluate predictors of GA-T outcomes in women with RA considering demographic, anthropometric, clinical, functional variables, and chest computed tomography (CT) findings. Forty-three women with RA underwent the GA-T, the N2SBW test, spirometry, measurement of the diffusing capacity for carbon monoxide (DLco), measurement of respiratory muscle strength, and evaluation of physical function of the lower and upper limbs through the Health Assessment Questionnaire Disability Index (HAQ-DI). Chest CT scans were analyzed retrospectively. The GA-T time showed significant correlations with the DLco (rs=-0.397, P=0.008), forced vital capacity/DLco (rs=0.307, P=0.044), phase III slope of the N2SBW test (SIIIN2, rs=0.644, P<0.0001), and the HAQ-DI (rs=0.482, P=0.001). Disease extent as assessed by chest CT was associated with the GA-T time. On multiple regression analysis, the SIIIN2 and HAQ-DI were the only predictors of the GA-T time, explaining 40% of its variability. Thus, ventilation distribution heterogeneity and worse physical function substantially explain the variability in GA-T time in women with RA and varying extents of disease on chest CT.
Anti-ceramide single-chain variable fragment mitigates radiation GI syndrome mortality independent of DNA repair

After 9/11, threat of nuclear attack on American urban centers prompted government agencies to develop medical radiation countermeasures to mitigate hematopoietic acute radiation syndrome (H-ARS) and higher-dose gastrointestinal acute radiation syndrome (GI-ARS) lethality. While repurposing leukemia drugs that enhance bone marrow repopulation successfully treats H-ARS in preclinical models, no mitigator potentially deliverable under mass casualty conditions preserves GI tract. Here, we report generation of an anti-ceramide 6B5 single-chain variable fragment (scFv) and show that s.c. 6B5 scFv delivery at 24 hours after a 90% lethal GI-ARS dose of 15 Gy mitigated mouse lethality, despite administration after DNA repair was complete. We defined an alternate target to DNA repair, an evolving pattern of ceramide-mediated endothelial apoptosis after radiation, which when disrupted by 6B5 scFv, initiates a durable program of tissue repair, permitting crypt, organ, and mouse survival. We posit that successful preclinical development will render anti-ceramide 6B5 scFv a candidate for inclusion in the Strategic National Stockpile for distribution after a radiation catastrophe.
Crystal structure of a far-red–sensing cyanobacteriochrome reveals an atypical bilin conformation and spectral tuning mechanism

Significance Phytochromes are well-known far-red-light sensors found in plants that trigger adaptive responses to facilitate competition for light capture with neighboring plants. Red- and far-red sensing are also critical for cyanobacteria living in the far-red–enriched shade of plants. This work reports the crystal structure of a far-red–sensing cyanobacteriochrome, a distant cyanobacterial relative of phytochrome. These studies shed insights into the molecular basis of far-red-sensing by phycobilin-based photoreceptors. Owing to the deep tissue penetration of far-red light, far-red–sensing cyanobacteriochromes are promising protein scaffolds for developing genetically encoded photoswitches, optoacoustic contrast agents, and fluorescent probes for in situ imaging and optogenetic applications. Cyanobacteriochromes (CBCRs) are small, linear tetrapyrrole (bilin)-binding photoreceptors in the phytochrome superfamily that regulate diverse light-mediated adaptive processes in cyanobacteria. More spectrally diverse than canonical red/far-red–sensing phytochromes, CBCRs were thought to be restricted to sensing visible and near UV light until recently when several subfamilies with far-red–sensing representatives (frCBCRs) were discovered. Two of these frCBCRs subfamilies have been shown to incorporate bilin precursors with larger pi-conjugated chromophores, while the third frCBCR subfamily uses the same phycocyanobilin precursor found in the bulk of the known CBCRs. To elucidate the molecular basis of far-red light perception by this third frCBCR subfamily, we determined the crystal structure of the far-red–absorbing dark state of one such frCBCR Anacy_2551g3 from Anabaena cylindrica PCC 7122 which exhibits a reversible far-red/orange photocycle. Determined by room temperature serial crystallography and cryocrystallography, the refined 2.7-Å structure reveals an unusual all-Z,syn configuration of the phycocyanobilin (PCB) chromophore that is considerably less extended than those of previously characterized red-light sensors in the phytochrome superfamily. Based on structural and spectroscopic comparisons with other bilin-binding proteins together with site-directed mutagenesis data, our studies reveal protein–chromophore interactions that are critical for the atypical bathochromic shift. Based on these analyses, we propose that far-red absorption in Anacy_2551g3 is the result of the additive effect of two distinct red-shift mechanisms involving cationic bilin lactim tautomers stabilized by a constrained all-Z,syn conformation and specific interactions with a highly conserved anionic residue.
Cascades of Risk Linking Intimate Partner Violence and Adverse Childhood Experiences to Less Sensitive Caregiving During Infancy

This study evaluated if maternal intimate partner violence (IPV) had indirect effects on sensitive parenting in infancy through prenatal depressive symptoms and postpartum parenting stress and if maternal adverse childhood experiences (ACEs) moderated these indirect effects. We hypothesized that: (a) IPV would be associated with greater prenatal depressive symptoms, which would predict greater postpartum parenting stress, and ultimately less sensitive parenting and (b) the link between IPV and depressive symptoms would be strongest for mothers with high ACEs. Participants included 295 mothers and their infants who were assessed prenatally and at 12 months postpartum. Path analyses indicated that mothers with higher IPV endorsed greater prenatal depressive symptoms, which was in turn associated with postpartum parenting stress, and ultimately less sensitive parenting behavior. Moderation analyses revealed that these indirect effects varied as a function of maternal ACEs, with the link between IPV and depressive symptoms only present for mothers who reported high ACEs. Because less sensitive caregiving is often an early indicator of child maltreatment risk, understanding precursors to sensitivity is critical to increase precision in parenting interventions designed to reduce risk for maltreatment. Results may inform evidence-based preventive interventions for mothers and infants at high-risk for child abuse and neglect.
Revealing the mechanisms behind novel auditory stimuli discrimination: An evaluation of silent functional MRI using looping star

Looping Star is a near‐silent, multi‐echo, 3D functional magnetic resonance imaging (fMRI) technique. It reduces acoustic noise by at least 25dBA, with respect to gradient‐recalled echo echo‐planar imaging (GRE‐EPI)‐based fMRI. Looping Star has successfully demonstrated sensitivity to the cerebral blood‐oxygen‐level‐dependent (BOLD) response during block design paradigms but has not been applied to event‐related auditory perception tasks. Demonstrating Looping Star's sensitivity to such tasks could (a) provide new insights into auditory processing studies, (b) minimise the need for invasive ear protection, and (c) facilitate the translation of numerous fMRI studies to investigations in sound‐averse patients. We aimed to demonstrate, for the first time, that multi‐echo Looping Star has sufficient sensitivity to the BOLD response, compared to that of GRE‐EPI, during a well‐established event‐related auditory discrimination paradigm: the “oddball” task. We also present the first quantitative evaluation of Looping Star's test–retest reliability using the intra‐class correlation coefficient. Twelve participants were scanned using single‐echo GRE‐EPI and multi‐echo Looping Star fMRI in two sessions. Random‐effects analyses were performed, evaluating the overall response to tones and differential tone recognition, and intermodality analyses were computed. We found that multi‐echo Looping Star exhibited consistent sensitivity to auditory stimulation relative to GRE‐EPI. However, Looping Star demonstrated lower test–retest reliability in comparison with GRE‐EPI. This could reflect differences in functional sensitivity between the techniques, though further study is necessary with additional cognitive paradigms as varying cognitive strategies between sessions may arise from elimination of acoustic scanner noise.
Approximating state-space manifolds which attract solutions of systems of delay-differential equations

Although the theory of delay-differential equations (DDEs) is generally best set in a function space, some systems of DDEs have solutions which, after the decay of transients, lie on a low-dimensional manifold in their state space. When the delay is small, highly accurate approximations to the state-space manifold which attracts the solutions can be constructed by a simple functional equation treatment. This allows the reduction of the original system of DDEs to a smaller system of ordinary differential equations. The simplified model obtained may be used to facilitate bifurcation analysis. The method is applied to two biochemical models, namely to a delay-differential version of Michaelis–Menten kinetics (the Brown model) and to a simple inducible operon model.
Bivalirudin in patients undergoing percutaneous coronary intervention and independent predictors of postoperative adverse events in these patients

Abstract The efficacy and safety of bivalirudin in percutaneous coronary intervention (PCI) has always been a hot topic in perioperative antithrombotic therapy, but there are still some controversies. So studies are needed to provide more evidence, especially the real world study which includes patients excluded from previous RCT studys. Our study aimed to investigate these information and analyze the independent predictors of postoperative adverse events. A retrospective study enrolled 1416 patients underwent PCI in Tianjin Chest Hospital from May 2016 to October 2017. The incidence of stent-thrombosis and net clinical adverse events, including all-cause death, myocardial infarction, stroke, urgent target-vessel revascularization and bleeding, were followed up for 30 days and 1 year. Logistic regression and COX regression were respectively used to analyze independent predictors of bleeding events within 30-days, and independent predictors of Major adverse cardiovascular and cerebrovascular events (MACCE) in patients with stent implantation within 1-year. Seven hundred six patients were treated with bivalirudin while 710 with unfractionated heparin (UFH). The proportions of diabetes, hypertension, anemia, myocardial-infarction history, PCI history, moderate-to-severe renal-impairment, gastrointestinal-bleeding history in the bivalirudin group were significantly higher (P < .05). Women, anemia were independent risk factors for bleeding within 30-days (P < .05). Among 682 patients with stent implantation in bivalirudin group, anemia, Body Mass Index (BMI) >25 kg/m2, KILLIP ≥2, ejection fraction (EF) <45%, eGFR <60 ml/minutes were independent risk factors for MACCE, while Statins, proton pump inhibitor (PPI) were independent protective factors for MACCE with-in 1-year (P < .05). Bivalirudin have good anticoagulant effect and lower bleeding risk during PCI, especially in patients with higher bleeding risk. In patients treated with bivalirudin, female, anemia were independent predictors of bleeding within 30-days, BMI >25 kg/m2, anemia, KILLIP ≥2, EF <45%, eGFR <60 ml/minutes were independent risk factors and Statins, PPI were independent protective factors of MACCE within 1-year.
Cecal microbial transplantation attenuates hyperthyroid‐induced thermogenesis in Mongolian gerbils

Endothermic mammals have a high energy cost to maintain a stable and high body temperature (Tb, around 37°C). Thyroid hormones are a major regulator for energy metabolism and Tb. The gut microbiota is involved in modulating host energy metabolism. However, whether the interaction between the gut microbiota and thyroid hormones is involved in metabolic and thermal regulations is unclear. We hypothesized that thyroid hormones via an interaction with gut microbiota orchestrate host thermogenesis and Tb. l‐thyroxine‐induced hyperthyroid Mongolian gerbils (Meriones unguiculatus) increased resting metabolic rate (RMR) and Tb, whereas Methimazole‐induced hypothyroid animals decreased RMR. Both hypothyroid and hyperthyroid animals differed significantly in faecal bacterial community. Hyperthyroidism increased the relative abundance of pathogenic bacteria, such as Helicobacter and Rikenella, and decreased abundance of beneficial bacteria Butyricimonas and Parabacteroides, accompanied by reduced total bile acids and short‐chain fatty acids. Furthermore, the hyperthyroid gerbils transplanted with the microbiota from control donors increased type 2 deiodinase (DIO2) expression in the liver and showed a greater rate of decline of both serum T3 and T4 levels and, consequently, a more rapid recovery of normal RMR and Tb. These findings indicate that thyroid hormones regulate thermogenesis depending on gut microbiota and colonization with normal microbiota by caecal microbial transplantation attenuates hyperthyroid‐induced thermogenesis. This work reveals the functional consequences of the gut microbiota‐thyroid axis in controlling host metabolic physiology and Tb in endotherms.
No Light, No Germination: Excitation of the Rhodospirillum centenum Photosynthetic Apparatus Is Necessary and Sufficient for Cyst Germination

Environmental cues that signal Gram-positive spores to germinate (termed germinants) have been identified for several Bacillus and Clostridium species. These studies showed that germinants are niche and species specific. ABSTRACT Rhodospirillum centenum is a Gram-negative alphaproteobacterium that is capable of differentiating into dormant cysts that are metabolically inactive and desiccation resistant. Like spores synthesized by many Gram-positive species, dormant R. centenum cysts germinate in response to an environmental signal, indicating that conditions favor survival and proliferation. Factors that induce germination are called germinants and are often both niche and species specific. In this study, we have identified photosynthesis as a niche-specific germinant for R. centenum cyst germination. Specifically, excitation of wild-type cysts suspended in a nutrient-free buffer with far-red light at >750 nm results in rapid germination. This is in stark contrast to mutant strains deficient in photosynthesis that fail to germinate upon exposure to far-red light under all assayed conditions. We also show that photosynthesis-induced germination occurs in a carbon- and nitrogen-free buffer even in strains that are deficient in carbon or nitrogen fixation. These results demonstrate that photosynthesis not only is necessary for germination but is itself sufficient for the germination of R. centenum cysts. IMPORTANCE Environmental cues that signal Gram-positive spores to germinate (termed germinants) have been identified for several Bacillus and Clostridium species. These studies showed that germinants are niche and species specific. For example, Clostridium difficile spores sense bile salts as a germinant as their presence informs these cells of an intestinal environment. Bacillus fastidiosus spores use uric acid as a germinant that is present in soil and poultry litter as this species inhabits poultry litter. It is evident from these studies that dormant cells sample their environment to assess whether conditions are advantageous for the propagation and survival of vegetative cells. To date, a limited number of germinants have been defined for only a few Gram-positive spore-forming species. Beyond that group, there is scant information on what cues signal dormant cells to exit dormancy. In our study, we show that the versatile Gram-negative photosynthetic bacterium Rhodospirillum centenum uses light-driven photosynthesis, and not the availability of nutrients, to trigger the germination of dormant cysts. This use of light-driven photosynthesis as a germinant is surprising as this species is also capable of growing under dark conditions using exogenous carbon sources for energy. Consequently, photosynthetic growth appears to be the preferred growth mechanism by this species.
Web-based physical activity intervention for people with progressive multiple sclerosis: application of consensus-based intervention development guidance

Objectives People with progressive multiple sclerosis (PwPMS) report that they recognise the benefits of activity on their physical and psychological health but need support to achieve their physical activity goals. We aimed to systematically develop a theoretically informed intervention that would enable PwPMS to more readily engage in regular physical activity. Design We used an intervention mapping approach to inform intervention development. Setting We conducted semistructured interviews with PwPMS and their families/carers and physiotherapists recruited from secondary care settings. Participants Fourteen PwPMS with an Expanded Disability Status Scale score of between 6 and 8 and 7 of their families/carers and 13 physiotherapists and 1 physiotherapy technician participated. Results Interview data suggested that the development of supportive coaching relationships with physiotherapists could promote the ability of PwPMS to achieve a desirable and achievable physical activity plan. These interview data informed the prototype ‘Lifestyle Exercise and Activity Package for Multiple Sclerosis’ (LEAP-MS) consisting of a secure multiuser web-based platform (with an education and activity suite, interactive components enabling selection of exercises, goal setting and activity logging), up to six flexible face-to-face or web-based physiotherapy coaching sessions and remote support via an embedded web-based messaging function that all together draw on specific theory-based methods to achieve physical activity behaviour change, namely active learning, reinforcement, modelling, feedback, facilitation, goal setting and guided practice. Implementation is within a multiuser platform accessible to participants, trained physiotherapists and researchers. Conclusions We have followed an inclusive, systematic and transparent process to develop the LEAP-MS intervention that enables detailed description of components, context and guiding principles to inform ongoing evaluation. Importantly, PwPMS expressed the need for autonomy in developing physical activity plans. This has been achieved through the embedding of self-management principles in the design and delivery of the LEAP-MS intervention.
Dynamical Behavior of Carbohydrates As Studied by Carbon-13 and Proton Nuclear Spin Relaxation

Variable-field carbon-13 and proton relaxation data are reported for two saccharides: a monosaccharide, 1,6-anhydro-β-d-galactopyranoside; and a disaccharide, methyl 3-O-α-d-mannopyranosyl-β-d-glucopyranoside. Carbon-13 measurements were perfomed at two fields, 4.7 and 9.4 T, and at 268, 288, and 303 K for the monosaccharide and at 268, 288, 303, and 323 K for the disaccharide. Proton cross-relaxation measurements were performed at three magnetic field strengths, 7.05, 9.4, and 11.75 T, and at several temperatures, 268, 288, and 303 K for the monosaccharide and 268, 282, 288, and 323 K for the disaccharide. The carbon-13 results were analyzed with the Lipari−Szabo “model-free” approach to obtain estimates of the global correlation times and order parameters. The monosaccharide was found to be very rigid, with S2 = 0.91, while the disaccharide showed some internal motions reflected in a lower order parameter, S2 around 0.8. The intra-ring proton cross-relaxation could be explained by the motional paramete.
The ChiS-Family DNA-Binding Domain Contains a Cryptic Helix-Turn-Helix Variant

Regulating gene expression is essential in all domains of life. This process is commonly facilitated by the activity of DNA-binding transcription factors. ABSTRACT Sequence-specific DNA-binding domains (DBDs) are conserved in all domains of life. These proteins carry out a variety of cellular functions, and there are a number of distinct structural domains already described that allow for sequence-specific DNA binding, including the ubiquitous helix-turn-helix (HTH) domain. In the facultative pathogen Vibrio cholerae, the chitin sensor ChiS is a transcriptional regulator that is critical for the survival of this organism in its marine reservoir. We recently showed that ChiS contains a cryptic DBD in its C terminus. This domain is not homologous to any known DBD, but it is a conserved domain present in other bacterial proteins. Here, we present the crystal structure of the ChiS DBD at a resolution of 1.28 Å. We find that the ChiS DBD contains an HTH domain that is structurally similar to those found in other DNA-binding proteins, like the LacI repressor. However, one striking difference observed in the ChiS DBD is that the canonical tight turn of the HTH is replaced with an insertion containing a β-sheet, a variant which we term the helix-sheet-helix. Through systematic mutagenesis of all positively charged residues within the ChiS DBD, we show that residues within and proximal to the ChiS helix-sheet-helix are critical for DNA binding. Finally, through phylogenetic analyses we show that the ChiS DBD is found in diverse proteobacterial proteins that exhibit distinct domain architectures. Together, these results suggest that the structure described here represents the prototypical member of the ChiS-family of DBDs. IMPORTANCE Regulating gene expression is essential in all domains of life. This process is commonly facilitated by the activity of DNA-binding transcription factors. There are diverse structural domains that allow proteins to bind to specific DNA sequences. The structural basis underlying how some proteins bind to DNA, however, remains unclear. Previously, we showed that in the major human pathogen Vibrio cholerae, the transcription factor ChiS directly regulates gene expression through a cryptic DNA-binding domain. This domain lacked homology to any known DNA-binding protein. In the current study, we determined the structure of the ChiS DNA-binding domain (DBD) and found that the ChiS-family DBD is a cryptic variant of the ubiquitous helix-turn-helix (HTH) domain. We further demonstrate that this domain is conserved in diverse proteins that may represent a novel group of transcriptional regulators.