Miracle-dz/UniFAR-FTUs huggingface dataset:
Phylogenomics Uncovers Evolutionary Trajectory of Nitrogen Fixation in Cyanobacteria

Abstract Biological nitrogen fixation (BNF) by cyanobacteria is of significant importance for the Earth’s biogeochemical nitrogen cycle but is restricted to a few genera that do not form monophyletic group. To explore the evolutionary trajectory of BNF and investigate the driving forces of its evolution, we analyze 650 cyanobacterial genomes and compile the database of diazotrophic cyanobacteria based on the presence of nitrogen fixation gene clusters (NFGCs). We report that 266 of 650 examined genomes are NFGC-carrying members, and these potentially diazotrophic cyanobacteria are unevenly distributed across the phylogeny of Cyanobacteria, that multiple independent losses shaped the scattered distribution. Among the diazotrophic cyanobacteria, two types of NFGC exist, with one being ancestral and abundant, which have descended from diazotrophic ancestors, and the other being anaerobe-like and sparse, possibly being acquired from anaerobic microbes through horizontal gene transfer. Interestingly, we illustrate that the origin of BNF in Cyanobacteria coincide with two major evolutionary events. One is the origin of multicellularity of cyanobacteria, and the other is concurrent genetic innovations with massive gene gains and expansions, implicating their key roles in triggering the evolutionary transition from nondiazotrophic to diazotrophic cyanobacteria. Additionally, we reveal that genes involved in accelerating respiratory electron transport (coxABC), anoxygenic photosynthetic electron transport (sqr), as well as anaerobic metabolisms (pfor, hemN, nrdG, adhE) are enriched in diazotrophic cyanobacteria, representing adaptive genetic signatures that underpin the diazotrophic lifestyle. Collectively, our study suggests that multicellularity, together with concurrent genetic adaptations contribute to the evolution of diazotrophic cyanobacteria.
Improving treatment of patients with psychosis in low-and-middle-income countries in Southeast Europe: Results from a hybrid effectiveness-implementation, pragmatic, cluster-randomized clinical trial (IMPULSE)

Abstract Background In Southeast Europe (SEE) standard treatment of patients with psychosis is largely based on pharmacotherapy with psychosocial interventions rarely available. DIALOG+ is a digital psychosocial intervention designed to make routine care therapeutically effective. This trial simultaneously examined effectiveness of DIALOG+ versus standard care on clinical and social outcomes (Aim 1) and explored intervention fidelity (Aim 2). Methods A hybrid type II effectiveness–implementation, cluster-randomized trial was conducted in five SEE countries: Bosnia and Herzegovina, Kosovo*, Montenegro, North Macedonia, and Serbia. The intervention was offered to patients six times across 12 months instead of routine care. The outcomes were subjective quality of life (primary), clinical symptoms, satisfaction with services, and economic costs. Intervention fidelity was operationalized as adherence to the protocol in terms of frequency, duration, content, and coverage. Data were analyzed using multilevel regression. Results A total of 81 clinicians and 468 patients with psychosis were randomized to DIALOG+ or standard care. The intervention was delivered with high fidelity. The average number of delivered sessions was 5.5 (SD = 2.3) across 12 months. Patients in the intervention arm had better quality of life (MANSA) at 6 months (p = 0.03). No difference was found for other outcomes at 6 months. Due to disruptions caused by the COVID-19 pandemic, 12-month data were not interpretable. Conclusions DIALOG+ improved subjective quality of life of individuals with psychosis at 6 months (after four sessions), albeit with small effect size. The intervention has the potential to contribute to holistic care of patients with psychosis.
The impact of narcolepsy on social relationships in young adults.

STUDY OBJECTIVES Narcolepsy often begins during adolescence and young adulthood which are crucial periods for social development. The symptoms of narcolepsy likely impact social interactions, but little research has assessed the effects of narcolepsy on social relationships. The current study investigated the impact of narcolepsy on friendships, and romantic and sexual relationships. METHODS Young adults (18-39 years) with narcolepsy were recruited through national narcolepsy patient organizations. Participants (N = 254) completed an online survey assessing their friendships, and romantic and sexual relationships, including communication about their social relationships with medical providers. RESULTS All participants (mean age = 28.8 years; 87% female, 92% White/Caucasian) reported that narcolepsy made their social life more challenging. They reported receiving more support from significant others, compared to family or friends (p<.05). Most (80%) indicated that narcolepsy currently impacted their sex life. Only a few participants reported that their providers asked about their social and sex lives, though they wanted providers to ask. CONCLUSIONS Narcolepsy impacts social functioning in young adults. Many individuals with narcolepsy prioritize single, meaningful, romantic relationships as developing and sustaining new relationships may be challenging. In addition, narcolepsy symptoms impact sexual functioning. Though many participants wanted to discuss their social and sex lives with providers, only a few providers ask. Treatment of narcolepsy in young adulthood should include supporting individuals regarding the impact on social, romantic, and sexual health.
Collagen VI deficiency causes behavioral abnormalities and cortical dopaminergic dysfunction

ABSTRACT Mutations of genes coding for collagen VI (COL6) cause muscle diseases, including Ullrich congenital muscular dystrophy and Bethlem myopathy. Although COL6 genetic variants were recently linked to brain pathologies, the impact of COL6 deficiency in brain function is still largely unknown. Here, a thorough behavioral characterization of COL6-null (Col6a1–/–) mice unexpectedly revealed that COL6 deficiency leads to a significant impairment in sensorimotor gating and memory/attention functions. In keeping with these behavioral abnormalities, Col6a1–/– mice displayed alterations in dopaminergic signaling, primarily in the prefrontal cortex. In vitro co-culture of SH-SY5Y neural cells with primary meningeal fibroblasts from wild-type and Col6a1–/– mice confirmed a direct link between COL6 ablation and defective dopaminergic activity, through a mechanism involving the inability of meningeal cells to sustain dopaminergic differentiation. Finally, patients affected by COL6-related myopathies were evaluated with an ad hoc neuropsychological protocol, revealing distinctive defects in attentional control abilities. Altogether, these findings point towards a previously undescribed role for COL6 in the proper maintenance of dopamine circuitry function and its related neurobehavioral features in both mice and humans. This article has an associated First Person interview with the first author of the paper.
Comparative studies of AlphaFold, RoseTTAFold and Modeller: a case study involving the use of G-protein-coupled receptors

Abstract Neural network (NN)-based protein modeling methods have improved significantly in recent years. Although the overall accuracy of the two non-homology-based modeling methods, AlphaFold and RoseTTAFold, is outstanding, their performance for specific protein families has remained unexamined. G-protein-coupled receptor (GPCR) proteins are particularly interesting since they are involved in numerous pathways. This work directly compares the performance of these novel deep learning-based protein modeling methods for GPCRs with the most widely used template-based software—Modeller. We collected the experimentally determined structures of 73 GPCRs from the Protein Data Bank. The official AlphaFold repository and RoseTTAFold web service were used with default settings to predict five structures of each protein sequence. The predicted models were then aligned with the experimentally solved structures and evaluated by the root-mean-square deviation (RMSD) metric. If only looking at each program’s top-scored structure, Modeller had the smallest average modeling RMSD of 2.17 Å, which is better than AlphaFold’s 5.53 Å and RoseTTAFold’s 6.28 Å, probably since Modeller already included many known structures as templates. However, the NN-based methods (AlphaFold and RoseTTAFold) outperformed Modeller in 21 and 15 out of the 73 cases with the top-scored model, respectively, where no good templates were available for Modeller. The larger RMSD values generated by the NN-based methods were primarily due to the differences in loop prediction compared to the crystal structures.
Individual and combined effects of land use and weeds on Cry1Ab/c protein expression and yield of transgenic cry1Ab/c rice

ABSTRACT Considering the anticipated commercial exploitation of insect-resistant transgenic rice and that the planting area of cultivated rice overlaps with wild rice, simulating an escape of transgenic rice from farmlands and exploring its fitness after entering semi-natural or natural ecosystems through uncontrolled seed dispersal or gene flow are critical to understand the resulting potential long-term environmental risks. The expression of foreign Cry1Ab/c protein and vegetative and reproductive fitness of insect-resistant transgenic rice Huahui1 (HH1) and its parental-line Minghui63 (MH63) were studied under four treatments combining land use and weed competition: farmland and uncultivated land under weed control (F-NW and U-NW, respectively), and farmland and uncultivated land without weed control (F-W and U-W, respectively). The expression of Cry1Ab/c was significantly lower in U-NW, F-W, and U-W than that in the control treatment, F-NW. Except for plant height, key vegetative (tiller number and biomass) and reproductive (grain number and grain weight per plant) growth indices of transgenic HH1 were significantly lower than those of the parental-line MH63 in F-NW and U-NW, indicating a significant fitness cost. In F-W and U-W, vegetative growth indices (plant height, tiller number, and biomass) were similar in HH1 and MH63; however, key reproductive indices including seed-set rate were significantly higher in HH1 than in MH63, indicating significant fitness benefits. Although these results support large-scale cultivation of insect-resistant transgenic rice in China, the ecological risk involved is high in farmland or uncultivated land without weed control (F-W and U-W).
Nanoscale mapping of shifts in dark plasmon modes in sub 10 nm aluminum nanoantennas

In this work, we report the fabrication and spectroscopic characterization of subwavelength aluminum nanocavities—consisting of hexamer or tetramer clusters of sub 10 nm width Al nanorods—with tunable localized surface plasmon resonance (LSPR) energies on suspended SiN x membranes. Here the volume plasmon (VP) and LSPR modes of lithographically-fabricated Al nanocavities are revealed by low-loss electron energy-loss spectroscopy (EELS) in an aberration corrected scanning transmission electron microscope (STEM). We show that the existence of grain boundaries (GBs) in these nanocavities results in shifts in the VP energy and a reduction in the VP lifetime. We map the VP energy and lifetime across GBs and we observe a decrease in VP energy and lifetime at GBs that is consistent with a reduction in free carrier density and increased plasmon scattering at these locations. Dipolar LSPR modes resonant in the UV and blue regions of the electromagnetic spectrum as well as higher-energy optically dark quadrupolar and hexapolar LSPR modes are also observed and mapped by STEM and EELS. All LSPR modes are confirmed via electromagnetic simulations based on the boundary element method. Both tetramer and hexamer structures support the excitation of dipolar bright and dipolar dark modes. Finally, we find that asymmetries in fabricated nanorod hexamer and tetramer nanocavities result in a mode mixing leading to a shift in dipolar dark LSPR modes.
Prevalence of multiple human papillomavirus infections and association with cervical lesions among outpatients in Fujian, China: A cross‐sectional study

Multiple human papillomavirus (HPV) infections are common, but their impact on cervical lesions remains controversial. A total of 6225 female patients who underwent colposcopies/conization following abnormal cervical cancer screening results were included in the study. The final pathological diagnosis was determined by the most severe pathological grade among the cervical biopsy, endocervical curettage, and conization. Univariate and multivariate logistic regression analyses were used to investigate the association between multiple HPV infections and cervical lesions, adjusting for age, HPV genotype, gravidity and parity. In total, 33.3% (n = 2076) of the study population was infected with multiple HPV genotypes. Multiple HPV infections were more prevalent in patients younger than 25 years and older than 55 years, with the rate of multiple HPV infections at 52.8% and 44.3%, respectively. HPV16\52\18\58 are the most common HPV genotypes and usually appear as a single infection. Compared to single HR‐HPV infection, multiple HR‐HPV infections do not increase the risk of HSIL+, while single HR‐HPV coinfected with LR‐HPV seems to reduce the risk of HSIL+ (odds ratio = 0.515, confidence interval: 0.370–0.719, p < 0.001). Multiple HR‐HPV infections cannot be risk‐stratified for triage of HR‐HPV‐positive women.
Roles of intestinal Parabacteroides in human health and diseases.

The stability of gut microbiota is essential for the host health. Parabacteroides spp. , core members of the human gut microbiota, have average abundance of 1.27% in the human of 12 populations. Parabacteroides has been recently reported to have a close relationship with host health (E.g., metabolic syndrome, inflammatory bowel disease and obesity). Parabacteroides have the physiological characteristics of carbohydrate metabolism and secreting SCFAs. However, antimicrobial resistance of Parabacteroides to antibiotic (such as clindamycin, moxifloxacin and cefoxitin) should not be ignored. In this review, we primarily focused on Parabacteroides distasoniss, Parabacteroides goldsteinii, Parabacteroides johnsonii and Parabacteroides merdae and discussed their relationships with host disease, diet and the prevention or induction of diseases. P. distasonis and P. goldsteinii may be viewed as the potential next generation probiotics (NGP) candidate due to their protective effects on inflammation and obesity in mice. We also discussed the potential therapeutic application of Parabacteroides spp. in maintaining host-intestine homeostasis.
Safety and effectiveness of empagliflozin and linagliptin fixed-dose combination therapy in Japanese patients with type 2 diabetes: final results of a one-year post-marketing surveillance study

ABSTRACT Background Fixed-dose combination (FDC) of the sodium-glucose co-transporter 2 inhibitor empagliflozin and the dipeptidyl peptidase-4 inhibitor linagliptin was approved for type 2 diabetes (T2D) treatment in Japan in 2018. We conducted a post-marketing surveillance study of empagliflozin/linagliptin FDC in routine clinical practice in Japan. Research design and methods This one-year, prospective, multicenter, observational study investigated the safety and effectiveness of empagliflozin/linagliptin FDC in Japanese patients with T2D. The primary outcome was incidence of adverse drug reactions (ADRs). Results Among 1146 patients, mean (SD) age was 63.8 (12.8) years and 22.08% were aged ≥75 years. Mean (SD) glycated hemoglobin (HbA1c) was 7.66% (1.21); fasting plasma glucose (FPG) was 142.90 mg/dl (43.75). ADRs were experienced by 32 (2.79%) patients (1 serious ADR); ADRs of important identified risk included urinary tract infection (7 patients [0.61%]), hypoglycemia (2 [0.17%]), ketoacidosis (0), genital infection (1 [0.09%]), and volume depletion (1 [0.09%]). Overall mean (SD) change from baseline in body weight, HbA1c, and FPG were −1.08 kg (3.21), −0.39% (1.11), and −7.90 mg/dl (39.12), respectively. Conclusions Empagliflozin/linagliptin FDC was effective and generally well tolerated in Japanese patients with T2D; no new safety concerns were identified. Trial Registration The trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT03761797)
Benefits of adrenal venous sampling with preoperative four-dimensional CT imaging

Background The effects of adrenal venous sampling (AVS) may be limited by the anatomical variants of adrenal veins. Purpose To investigate the benefits of AVS for patients who underwent four-dimensional computed tomography (4D CT) before AVS. Material and Methods We reviewed the images of contrast-enhanced four phase three-dimensional (3D) and 4D CT in patients who received AVS between February 2010 and February 2021. A total of 112 patients (59 women; mean age = 55.3 ± 11.8 years) were enrolled. Of the entire population, 49.1% (55/112) underwent 4D CT, whereas 50.9% (57/112) underwent 3D CT. The anatomical features of adrenal veins and procedural data were obtained. Simple linear regression analyses were performed to determine the relationship between imaging protocols and AVS. Results On comparison of the two groups, the 4D cohort had a higher success rate (98.2% vs. 78.9%; P = 0.001), shorter procedure and fluoroscopy time (73.6 ± 37.3 min vs. 110.5 ± 47.9 min; P < 0.001 and 28.7 ± 31.2 min vs. 97.4 ± 251.7 min; P = 0.047, respectively), lower radiation exposure (243.5 ± 315.5 mGycm2 vs. 613.4 ± 674.6 mGycm2; P < 0.001) and less contrast volume (46.2 ± 42.7 ml vs. 68.3 ± 47.4 ml vs; P = 0.014). In simple linear regression analysis, positive and negative identification of right adrenal vein before AVS significantly influenced the success rate (unstandardized coefficients [UC] = 0.304, standardized coefficients [SC] = 0.304; P = 0.001) and operation duration (UC = −46.124, SC = −0.318; P = 0.001). Conclusion Pre-procedural 4D CT may facilitate successful AVS. Compared with four-phase 3D CT, this protocol is better to shorten the operation and fluoroscopy time, and to reduce the radiation dose and contrast consumption.
A survey on the management of thyroid eye disease among American and European Thyroid Association members.

BACKGROUND The thyroid eye disease (TED) treatment landscape is rapidly evolving. How new treatment options have impacted practice is unknown. METHODS We conducted a cross-sectional electronic survey of American and European Thyroid Association members between June 2 and June 30, 2021. The survey included TED questions about resources for its management, index cases for different severities and presentations of TED, barriers for the management of TED, and participants' concerns about TED. We classified respondents into three geographic categories: North America, Europe, or other regions. RESULTS 252 eligible participants started the survey (15% response rate), and 227 completed it. Participants were mostly men (50.2%,114/227), white (79.7%,181/227), endocrinologists with a thyroid focus (66.1%, 150/227), practicing in a tertiary academic center (46.7%,106/227), caring for 10 or more TED patients over the last 12 months (40.5%) and reported not having a multidisciplinary TED clinic in their institution (52.8%). The majority reported that new TED cases per annum have not changed in the last 10 years (47.5%, 108/227), and that TED patients are found in practice during the management of hyperthyroidism (41.8%, 95/227). For mild active TED, participants from Europe reported higher use of selenium (73%[96/132] vs. 32%[20/62] of respondents from North America and 24%[8/33] of respondents from other regions). For moderate-to-severe active TED, there was a modest preference for teprotumumab as first-line therapy (37%, 23/62) among North American participants and intravenous steroids (IV) ( 73%[96/132], and 42%[14/33]) for participants from Europe and other regions, respectively. These treatment preferences did not change in patients with moderate-to-severe active TED with poorly controlled diabetes. In contrast, participants from the three geographic categories preferred IV steroids for optic neuropathy and women planning pregnancy. The three top "very important" concerns about TED management according to participants were: the cost of TED treatment (31.3%,71/227), lack of effective TED treatments (19.8%,45/227), and difficulty in predicting if TED will develop (18.9%,43/227). CONCLUSIONS There is a marked geographic practice variation in the management of TED. Clinicians' concerns about TED management demand ongoing research on more effective treatment, TED predictive tools, and policy changes to improve the affordability of new TED therapies.
Local Functional Connectivity as a Parsimonious Explanation of the Main Frameworks for ADHD in Medication-Naïve Adults

Objective: Neuroimaging studies in children with ADHD indicate that their brain exhibits an atypical functional connectivity pattern characterized by increased local connectivity and decreased distant connectivity. We aim to evaluate if the local and distant distribution of functional connectivity is also altered in adult samples with ADHD who have never received medication before. Methods: We compared local and distant functional connectivity between 31 medication-naïve adults with ADHD and 31 healthy controls and tested whether this pattern was associated with symptoms severity scores. Results: ADHD sample showed increased local connectivity in the dACC and the SFG and decreased local connectivity in the PCC. Conclusion: Results parallel those obtained in children samples suggesting a deficient integration within the DMN and segregation between DMN, FPN, and VAN. These results are consistent with the three main frameworks that explain ADHD: the neurodevelopmental delay hypothesis, the DMN interference hypothesis and multi-network models.
Improving the accuracy of circadian lighting simulation with field measurement

For improving the simulation accuracy of circadian lighting, a workflow was established to first calibrate the simulation model under electric lighting followed by validation with integrated daylighting and electric lighting. A case study was conducted in a daylit office, with the evident impact of varying lighting parameters (light level, intensity, SPD, reflectance) on the simulation accuracy. In the fully calibrated model, the simulated and field-measured SPDs are highly correlated (rSPD ≥ 0.9), providing the acceptable accuracy of the simulated melanopic/photopic(M/P) ratio with the error rate (MBErel) less than 4% and residual deviation (RMSErel) within 7%. The MBErel and RMSErel of corneal illuminance (EV), EML, and CS are within 10% and 20%, respectively. The ratio of data points with the residual rate (e) less than 20% is over 75% in the calibration and validation phases. Conclusively, the proposed procedure could help prepare for further analysis of circadian light exposure.
A filtering-based methodology for assessing evacuation performance in layout of complex infrastructures

Evacuation is a performance matter in buildings design, and this study provides a framework for assessing the performance of complex architectural layouts for emergency egress. First, a theoretical framework is inspired by advanced estimation methods and extended to a performance model with spatial and computational sub-models. The spatial sub-model abstracts the floorplan as a geometric network. The computational sub-model is consisted of: filtering parameters, routing algorithm, and bottleneck importance calculation. A criterion called ‘Bottleneck Importance (BI)’ is introduced and formulated, which shows the effect of obstruction in each position in route on the evacuation performance of the floor. The model is applied in a case study, and outputs made it possible to analyse the performance of exits in-floor evacuation, frequent positions in the evacuation route, the topological relationship with performance, especially at intersections, and the effect of blocking in egress corridors and cause of obstructions.