Miracle-dz/UniFAR-FTUs huggingface dataset:
Insights into cyanobacterial alkane biosynthesis

Abstract Alkanes are high-energy molecules that are compatible with enduring liquid fuel infrastructures, which make them highly suitable for being next-generation biofuels. Though biological production of alkanes has been reported in various microorganisms, the reports citing photosynthetic cyanobacteria as natural producers have been the most consistent for the long-chain alkanes and alkenes (C15–C19). However, the production of alkane in cyanobacteria is low, leading to its extraction being uneconomical for commercial purposes. In order to make alkane production economically feasible from cyanobacteria, the titre and yield need to be increased by several orders of magnitude. In the recent past, efforts have been made to enhance alkane production, although with a little gain in yield, leaving space for much improvement. Genetic manipulation in cyanobacteria is considered challenging, but recent advancements in genetic engineering tools may assist in manipulating the genome in order to enhance alkane production. Further, advancement in a basic understanding of metabolic pathways and gene functioning will guide future research for harvesting the potential of these tiny photosynthetically efficient factories. In this review, our focus would be to highlight the current knowledge available on cyanobacterial alkane production, and the potential aspects of developing cyanobacterium as an economical source of biofuel. Further insights into different metabolic pathways and hosts explored so far, and possible challenges in scaling up the production of alkanes will also be discussed.
Downbeat Nystagmus in Episodic Ataxia Type 1 Associated with a Novel KCNA1 Mutation

Caroline Decaix, PhD, Nadya Pyatigorskaya, MD, PhD, Graziella Mangone, MD, PhD, Romain Valabrègue, PhD, Isabelle Arnulf, MD, PhD, Florence Cormier, MD, Suzanne Lesage, PhD, Stephane Lehericy, MD, PhD, Philippe Remy, MD, PhD, Alexis Brice, MD, and Jean-Christophe Corvol, MD, PhD* Institut du Cerveau Paris Brain Institute ICM, Sorbonne University, INSERM, CNRS, Paris, 75013, France, Centre d’Investigation Clinique Neurosciences, Department of Neurology, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, 75013, France, Université Paris-Saclay, CEA, CNRS, MIRCen, Laboratoire des Maladies Neurodégénératives, Fontenayaux-Roses, 92265, France, Department of Neurology, Assistance Publique Hôpitaux de Paris, Hôpital Saint-Antoine, Paris, 75012, France, Department of Neuroradiology, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, 75013, France, Sleep Disorders Unit, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, 75013, France, Centre Expert Parkinson I Equipe NPI, Department of Neurology, Assistance Publique Hôpitaux de Paris, Hôpital Henri Mondor, INSERM IMRB, Université Paris-Est, Créteil, 94000, France, Département d’ Etudes Cognitives, Ecole Normale Supérieure, Paris, 75005, France, and Department of Genetics, Assistance Publique Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Paris, 75013, France
Diet and food type affect urinary pesticide residue excretion profiles in healthy individuals: results of a randomized controlled dietary intervention trial.

BACKGROUND Observational studies have linked pesticide exposure to various diseases, whereas organic food consumption has been associated with positive health outcomes. Organic farming standards prohibit the use of most pesticides, and organic food consumption may therefore reduce pesticide exposure. OBJECTIVES To determine the effects of diet (Western compared with Mediterranean) and food type (conventional compared with organic) and sex on urinary pesticide residue excretion (UPRE), as well as associations between specific diet components and UPRE. METHODS In this 2-wk, randomized dietary intervention trial, healthy adults were randomly allocated to an intervention (n = 13) or conventional (n = 14) group. Whereas participants in the intervention group consumed a Mediterranean diet (MedDiet) made entirely from organic foods, the conventional group consumed a MedDiet made entirely from conventional foods. Both groups consumed habitual Western diets made from conventional foods before and after the 2-wk intervention period. The primary outcome was UPRE. In addition, we assessed diet composition and pesticide residue profiles in foods eaten. Participants were aware of group assignment, but the study assessors were not. RESULTS During the intervention period, total UPRE was 91% lower with organic (mean 17 μg/d; 95% CI: 15, 19) than with conventional (mean 180 μg/d; 95% CI: 153, 208) food consumption (P < 0.0001). In the conventional group, switching from the habitual Western diet to the MedDiet increased insecticide excretion from 7 to 25 μg/d (P < 0.0001), organophosphate excretion from 5 to 19 μg/d (P < 0.0001), and pyrethroid residue excretion from 2.0 to 4.5 μg/d (P < 0.0001). Small but significant effects of sex were detected for chlormequat, herbicide, and total pesticide residue excretion. CONCLUSIONS Changing from a habitual Western diet to a MedDiet was associated with increased insecticide, organophosphate, and pyrethroid exposure, whereas organic food consumption reduced exposure to all groups of synthetic chemical pesticides. This may explain the positive health outcomes linked to organic food consumption in observational studies. This trial was registered at www.clinicaltrials. gov as NCT03254537.
Para-Sports can Promote Functional Reorganization in the Ipsilateral Primary Motor Cortex of Lower Limbs Amputee

Background. Drastic functional reorganization was observed in the ipsilateral primary motor cortex (M1) of a Paralympic long jumper with a unilateral below-knee amputation in our previous study. However, it remains unclear whether long-term para-sports are associated with ipsilateral M1 reorganization since only 1 athlete with amputation was investigated. Objective. This study aimed to investigate the relationship between the long-term para-sports and ipsilateral M1 reorganization after lower limb amputation. Methods. Lower limb rhythmic muscle contraction tasks with functional magnetic resonance imaging and T1-weighted structural imaging were performed in 30 lower limb amputees with different para-sports experiences in the chronic phase. Results. Brain activity in the ipsilateral primary motor and somatosensory areas (SM1) as well as the contralateral dorsolateral prefrontal cortex, SM1, and inferior temporal gyrus showed a positive correlation with the years of routine para-sports participation (sports years) during contraction of the amputated knee. Indeed, twelve of the 30 participants who exhibited significant ipsilateral M1 activation during amputated knee contraction had a relatively longer history of para-sports participation. No significant correlation was found in the structural analysis. Conclusions. Long-term para-sports could lead to extensive reorganization at the brain network level, not only bilateral M1 reorganization but also reorganization of the frontal lobe and visual pathways. These results suggest that the interaction of injury-induced and use-dependent cortical plasticity might bring about drastic reorganization in lower limb amputees.
Health-Related Quality of Life in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Cross-Sectional Study

ABSTRACT Background The percutaneous coronary intervention (PCI) is the most common treatment for coronary artery disease. Health-related quality of life (HRQoL), alongside mortality and recurrence rates, is a key outcome indicator for PCI. Purpose The aim of this study was to investigate the factors influencing HRQoL in patients with coronary artery disease who had received PCI. Methods A convenience sample from the cardiovascular center of a tertiary hospital in South Korea was recruited for this descriptive, cross-sectional study. This study was conducted using a structured questionnaire and patients' medical records on a sample of 210 patients with coronary artery disease who were ≥ 18 years old and > 1 month post-PCI. The questionnaire collected information on general, clinical, and psychosocial characteristics. Data were analyzed using descriptive statistics, independent t test, one-way analysis of variance, the Scheffé test, and the Pearson correlation test. A multiple linear regression, together with the significant variables in univariate analysis, was used to determine the variables that significantly influenced HRQoL. Results HRQoL was found to vary significantly with age, marital status, subjective economic status, primary caregiver, duration since first PCI, New York Heart Association class, anxiety, depression, and social support. The significant general characteristics shown to affect HRQoL in patients who had undergone PCI included age, marital status, and primary caregiver. The significant clinical characteristics shown to affect HRQoL included duration from first PCI and New York Heart Association class. The significant psychosocial characteristics shown to affect HRQoL included anxiety and depression. Primary caregiver and New York Heart Association class were identified as having the greatest impact on HRQoL in the PCI patients in this study. Conclusions To enhance HRQoL in patients who had received PCI, their post-PCI physical and psychological symptoms should be regularly assessed. Furthermore, intervention strategies aimed to improve quality of life in patients with severe functional limitations and those receiving family care are necessary.
Adoption of E-health platforms by medical practitioners: Mediating effect of attitude on E-health platforms usage

Abstract This study considers Theory of Reasoned Action and Technology Acceptance Model frameworks to test the mediating role of attitude towards using E-health platforms. 224 medical practitioners’ responses are collected in the online mode. The mediation analysis supports the full mediation role of attitude towards using the E-health platforms in the relationship between perceived usefulness and intentions to use with (indirect effect = .15, SE = 0.03, LLCI = 0.09, and ULCI = .22). E-health platform developers should take active measures to improve the attitude of medical practitioners towards using such platforms, to derive the best results of the added features.
Clinical and immunological characteristics of bee venom hypersensitivity among beekeepers in Thailand.

BACKGROUND Bee venom (BV) hypersensitivity can be severe and potentially life-threatening. Beekeepers heavily exposed to bee stings and are thus at a high-risk group. The data on bee sting reactions among beekeepers in Thailand is limited. OBJECTIVE To determine the prevalence, clinical and immunological characteristics, and the knowledge of BV hypersensitivity in Thai beekeepers. METHODS A self-reported questionnaire survey about BV reactions in beekeepers were conducted. Further blood test for immunological parameters: serum BV-specific IgE (BV sIgE), phospholipase A2-specific IgE (Api m1 sIgE), and BV-specific IgG4 (BV sIgG4) were compared between non-allergic beekeepers, patients with a history of bee sting anaphylaxis and the non-allergic control group. RESULTS A total of 202 out of 447 questionnaires (response rate 45%) were returned. The median age was 46.7 years. Systemic reactions were documented in 6.4%. Younger than 45 years was found to be a factor associated with systemic reactions (OR, 4.35; 95% CI, 1.16-16.31). The BV sIgE and Api m1 sIgE were significantly higher in the anaphylaxis group (p = 0.001). The median of BV sIgG4 was significantly higher in non-allergic beekeepers (p = 0.001). For the knowledge of BV hypersensitivity, 56.4% recognized that BV hypersensitivity could be fatal but only 6% knew about epinephrine auto-injector device. CONCLUSIONS The prevalence of systemic reactions after stings among Thai beekeepers was not high, which might be due to the tolerance induced by natural exposure via sIgG4. The level of knowledge of BV hypersensitivity among beekeepers was insufficient, more education must be provided.
Significance of boost radiotherapy in early invasive ductal breast cancer with ductal carcinoma in situ component under negative surgical margins

Abstract We hypothesize that there is a risk of ipsilateral breast tumor recurrence (IBTR) in surgical margin-free invasive ductal carcinoma (IDC) in the presence of ductal carcinoma in situ (DCIS) component affecting surgical margins in early stage. From 1990 to 2014, 343 patients with IDC in which the DCIS component constitute have received radiotherapy (RT) following breast-conserving surgery (BCS). All patients received whole breast irradiation with a prescribed dose of 50 Gy in 20 fractions (four times a week). This one-arm cohort with boost RT (253 patients) was compared for IBTR with a non-cohort group receiving no boost RT because of freedom from positive margins (90 patients). Median observation months were 98 (boost group) vs 119 (no boost group), respectively. The 15-year local recurrence-free survival (LRFS) rates were 98.5% and 85.6% in the boost and no boost groups, respectively (Cox proportional hazards model univariate analysis; p = 0.013, HR 0.13). Similarly, for other background factors, there was a significant difference in the LRFS between age groups. The 15-year LRFS rate was 91.8% in patients aged 45 years or younger and 94.6% in patients older than 46 years (p = 0.031, HR 0.21), respectively. Only these two factors were independently significant in Cox proportional hazards model multivariate analysis. IBTR risk in margin-free IDC with DCIS component was independently decreased by boost RT in the cohort setting. Tumor size, extensive intraductal component (EIC), boost dose, the presence of lymph node (LN) metastasis and hormonal therapy were not IBTR risk factors in this study.
Spectrum of sublytic astrocytopathy in neuromyelitis optica

Abstract Neuromyelitis optica is an autoimmune inflammatory disorder targeting aquaporin-4 water channels in CNS astrocytes. Histopathological descriptions of astrocytic lesions reported in neuromyelitis optica so far have emphasized a characteristic loss of aquaporin-4, with deposition of IgG and complement and lysis of astrocytes, but sublytic reactions have been underappreciated. We performed a multi-modality study of 23 neuromyelitis optica autopsy cases (clinically and/or pathologically confirmed; 337 tissue blocks). By evaluating astrocytic morphology, immunohistochemistry and AQP4 RNA transcripts, and their associations with demyelinating activity, we documented a spectrum of astrocytopathy in addition to complement deposition, microglial reaction, granulocyte infiltration and regenerating activity. Within advanced demyelinating lesions, and in periplaque areas, there was remarkable hypertrophic astrogliosis, more subtle than astrocytic lysis. A degenerative component was suggested by ‘dystrophic’ morphology, cytoplasmic vacuolation, Rosenthal fibres and associated stress protein markers. The abundance of AQP4 mRNA transcripts in sublytic reactive astrocytes devoid of aquaporin-4 protein supported in vivo restoration following IgG-induced aquaporin-4 endocytosis/degradation. Astrocytic alterations extending beyond demyelinating lesions speak to astrocytopathy being an early and primary event in the evolving neuromyelitis optica lesion. Focal astrocytopathy observed without aquaporin-4 loss or lytic complement component deposition verifies that astrocytic reactions in neuromyelitis optica are not solely dependent on IgG-mediated aquaporin-4 loss or lysis by complement or by IgG-dependent leucocyte mediators. We conclude that neuromyelitis optica reflects a global astrocytopathy, initiated by binding of IgG to aquaporin-4 and not simply definable by demyelination and astrocytic lysis. The spectrum of astrocytic morphological changes in neuromyelitis optica attests to the complexity of factors influencing the range of astrocytic physiological responses to a targeted attack by aquaporin-4-specific IgG. Sublytic astrocytic reactions are no doubt an important determinant of the lesion’s evolution and potential for repair. Pharmacological manipulation of the astrocytic stress response may offer new avenues for therapeutic intervention.
Resilience and recovery from sports related concussion in adolescents and young adults

ABSTRACT Introduction Recovery and return to play are important milestones for athletes who sustain sport-related concussions (SRC). Several factors have been shown to influence resolution of post-concussion related symptoms (PCS), but resilience, a trait that reflects the ability to overcome adversity, is another factor that may influence recovery. The aim of this study was to determine the relationship of resilience with resolution of symptoms during recovery in adolescents and young adults following SRC. Method This prospective study is part of the North Texas Concussion Registry (ConTex). Subjects (N = 332) aged 13 to 25 years who sustained a SRC within 10 days of presenting to clinic were evaluated at two time points: initial clinical visit and three-month follow-up. Resilience was measured by the self-report Brief Resilience Survey (BRS) and PCS by the Sport Concussion Assessment Tool-5 Symptom Evaluation Post-Concussion Symptom Scale (PCSS). Recovery was determined by self-reported return to sports/physical activity and percent back to normal. Results Repeated measures ANCOVA and linear regression models showed that lower resilience ratings at initial visit were associated with a greater number and severity of PCSS symptoms along with higher levels of anxiety and depression symptoms during recovery from SRC. At three months, subjects with lower initial resilience ratings were less likely to report feeling back to normal and had greater aggravation of symptoms from physical and cognitive activity even when they had returned to sports/physical activity. Conclusions Lower resilience was associated with greater symptoms and delayed recovery from SRC. Results suggest that resilience may be another important factor to address in recovery from SRC. Future research is needed to examine the extent to which resilience measured after SRC reflects pre-injury characteristics and to better inform the development of interventions to promote resilience during recovery.
An integrative NMR-SAXS approach for structural determination of large RNAs defines the substrate-free state of a trans-cleaving Neurospora Varkud Satellite ribozyme

Abstract The divide-and-conquer strategy is commonly used for protein structure determination, but its applications to high-resolution structure determination of RNAs have been limited. Here, we introduce an integrative approach based on the divide-and-conquer strategy that was undertaken to determine the solution structure of an RNA model system, the Neurospora VS ribozyme. NMR and SAXS studies were conducted on a minimal trans VS ribozyme as well as several isolated subdomains. A multi-step procedure was used for structure determination that first involved pairing refined NMR structures with SAXS data to obtain structural subensembles of the various subdomains. These subdomain structures were then assembled to build a large set of structural models of the ribozyme, which was subsequently filtered using SAXS data. The resulting NMR-SAXS structural ensemble shares several similarities with the reported crystal structures of the VS ribozyme. However, a local structural difference is observed that affects the global fold by shifting the relative orientation of the two three-way junctions. Thus, this finding highlights a global conformational change associated with substrate binding in the VS ribozyme that is likely critical for its enzymatic activity. Structural studies of other large RNAs should benefit from similar integrative approaches that allow conformational sampling of assembled fragments.
Suppression of telomere capping defects of Saccharomyces cerevisiae yku70 and yku80 mutants by telomerase

Abstract The Ku complex performs multiple functions inside eukaryotic cells, including protection of chromosomal DNA ends from degradation and fusion events, recruitment of telomerase, and repair of double-strand breaks (DSBs). Inactivation of Ku complex genes YKU70 or YKU80 in cells of the yeast Saccharomyces cerevisiae gives rise to mutants that exhibit shortened telomeres and temperature-sensitive growth. In this study, we have investigated the mechanism by which overexpression of telomerase suppresses the temperature sensitivity of yku mutants. Viability of yku cells was restored by overexpression of the Est2 reverse transcriptase and TLC1 RNA template subunits of telomerase, but not the Est1 or Est3 proteins. Overexpression of other telomerase- and telomere-associated proteins (Cdc13, Stn1, Ten1, Rif1, Rif2, Sir3, and Sir4) did not suppress the growth defects of yku70 cells. Mechanistic features of suppression were assessed using several TLC1 RNA deletion derivatives and Est2 enzyme mutants. Supraphysiological levels of three catalytically inactive reverse transcriptase mutants (Est2-D530A, Est2-D670A, and Est2-D671A) suppressed the loss of viability as efficiently as the wild-type Est2 protein, without inducing cell senescence. Roles of proteins regulating telomere length were also determined. The results support a model in which chromosomes in yku mutants are stabilized via a replication-independent mechanism involving structural reinforcement of protective telomere cap structures.
Patient-reported outcome measures in systemic lupus erythematosus by a web-based application: A randomized, crossover, agreement study

Objectives Patient-reported outcome measures (PROMs) are evaluated in randomized controlled trials (RCTs) in patients with systemic lupus erythematosus (SLE), but not widely used in clinical practice. However, interest in incorporating PROMs into the management of SLE is increasing as PROMs provide a unique insight into the patient’s perception of lupus disease activity. The objective was to assess agreement in PROMs answered using a web app versus an outpatient touchscreen among patients with SLE. Methods In a crossover RCT, SLE patients answered the following PROMs in a random order using the web app and the outpatient touchscreen: Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) Global Health, SLAQ Symptom, SLAQ Total, SLAQ Worsening, Pain Visual Analog Scale (VAS), Fatigue VAS, Patient Global Health VAS, Health Assessment Questionnaire Disability Index (HAQ-DI), Patient Acceptable Symptom State (PASS), and an Anchoring Question. Equivalence between the two device types was demonstrated if the 95% confidence interval (95% CI) of the difference in PROM scores was within the prespecified equivalence margin. Agreement between the two device types was assessed using mixed linear models. Results Thirty-four patients with SLE were included. Equivalence was demonstrated between the two device types for SLAQ Global Health with a difference of −0.21 (95% CI: −0.65 to 0.23). Moreover, equivalence was also found for HAQ-DI, Pain VAS, and Fatigue VAS whereas only comparability within the limits of the Minimal Clinically Important Difference (MCID) was demonstrated for VAS Patient Global Health. Statistical comparability was demonstrated for SLAQ Total, SLAQ Worsening, PASS, and Anchoring Question (no predefined MCID/equivalence margins available). However, a statistically significant difference between device types was observed for the SLAQ Symptom of −0.56 (95% CI: −1.10 to −0.01). The difference was, however, very small when considering the scale range of 0–24; thus, it was not judged to be of clinical relevance. Preference for the web app was very high (91.2%). Conclusion For the first time ever, equivalence and comparability between two electronic device types for various PROMs were demonstrated among patients with SLE. Implementation of the device is expected to improve the management of SLE.