Miracle-dz/UniFAR-FTUs huggingface dataset:
Gut dysbiosis impairs hippocampal plasticity and behaviors by remodeling serum metabolome

ABSTRACT Accumulating evidence suggests that gut microbiota as a critical mediator of gut-brain axis plays an important role in human health. Altered gut microbial profiles have been implicated in increasing the vulnerability of psychiatric disorders, such as autism, depression, and schizophrenia. However, the cellular and molecular mechanisms underlying the association remain unknown. Here, we modified the gut microbiome with antibiotics in newborn mice, and found that gut microbial alteration induced behavioral impairment by decreasing adult neurogenesis and long-term potentiation of synaptic transmission, and altering the gene expression profile in hippocampus. Reconstitution with normal gut flora produced therapeutic effects against both adult neurogenesis and behavioral deficits in the dysbiosis mice. Furthermore, our results show that circulating metabolites changes mediate the effect of gut dysbiosis on hippocampal plasticity and behavior outcomes. Elevating the serum 4-methylphenol, a small aromatic metabolite produced by gut bacteria, was found to induce autism spectrum disorder (ASD)-like behavior impairment and hippocampal dysfunction. Together our finding demonstrates that early-life gut dysbiosis and its correlated metabolites change contribute to hippocampal dysfunction and behavior impairment, hence highlight the potential microbiome-mediated therapies for treating psychiatric disorders.
Recombinant human platelet‐derived growth factor improves root coverage of a collagen matrix for multiple adjacent gingival recessions: A triple‐blinded, randomized, placebo‐controlled trial

Abstract Aim To evaluate the efficacy of recombinant human platelet‐derived growth factor (rhPDGF)‐BB combined with a cross‐linked collagen matrix (CCM) for the treatment of multiple adjacent gingival recession type 1 defects (MAGRs) in combination with the coronally advanced flap (CAF). Materials and Methods Thirty patients were enrolled in this triple‐blind, randomized, placebo‐controlled trial and treated with either CAF + CCM + rhPDGF, or CAF + CCM + saline. The primary outcome was mean root coverage (mRC) at 6 months. Complete root coverage, gain in gingival thickness (GT), keratinized tissue width, volumetric and ultrasonographic changes, and patient‐reported outcome measures were also assessed. Mixed‐modelling regression analyses were used for statistical comparisons. Results At 6 months, the mRC of the CCM + rhPDGF and CCM alone groups were 88.25% and 77.72%, respectively (p = .02). A significant gain in GT was consistently observed for both treatment arms, and more so for the patients receiving the matrix containing rhPDGF through time (0.51 vs. 0.80 mm, on average, p = .01). The rhPDGF + CCM treated patients presented greater volume gain, higher soft tissue thickness, and a superior aesthetic score. Conclusion rhPDGF enhances the clinical, volumetric, and aesthetic outcomes of MAGRs above the results achieved with CAF + CCM alone (ClinicalTrials.gov NCT04462237).
Do pupillary responses during authentic slot machine use reflect arousal or screen luminance fluctuations? A proof-of-concept study

Modern slot machines are among the more harmful forms of gambling. Psychophysiological measures may provide a window into mental processes that underpin these harms. Here we investigated pupil dilation derived from eye tracking as a means of capturing changes in sympathetic nervous system arousal following outcomes on a real slot machine. We hypothesized that positively reinforcing slot machine outcomes would be associated with increases in arousal, reflected in larger pupil diameter. We further examined the contribution of game luminance fluctuations on pupil diameter. In Experiment 1A, experienced slot machine gamblers (N = 53) played a commercially-available slot machine in a laboratory for 20 minutes while wearing mobile eye tracking glasses. Analyses differentiated loss outcomes, wins, losses-disguised-as-wins, and (free-spin) bonus features. Bonus features were associated with rapid increases in pupil diameter following the onset of outcome-related audiovisual feedback, relative to losses. In Experiment 1B, luminance data were extracted from captured screen videos (derived from Experiment 1A) to characterize on-screen luminance changes that could modulate pupil diameter. Bonus features and wins were associated with pronounced and complex fluctuations in screen luminance (≈50 L and ≈25L, respectively). However, the pupil dilation that was observed to bonus features in Experiment 1A coincided temporally with only negligible changes in screen luminance, providing partial evidence that the pupil dilation to bonus features may be due to arousal. In Experiment 2, 12 participants viewed pairs of stimuli (scrambled slot machine images) at luminance difference thresholds of ≈25L, ≈50L, and ≈100L. Scrambled images presented at luminance differences of ≈25L and greater were sufficient to cause pupillary responses. Overall, pupillometry may detect event-related changes in sympathetic nervous system arousal following gambling outcomes, but researchers must pay careful attention to substantial in-game luminance changes that may confound arousal-based interpretations.
Dynamic Sublimes, Changing Plans, and The Legacy of A Megaproject: The Case of the 1966 Soccer World Cup

Global sporting events such as the FIFA (Fédération Internationale de Football Association) World Cup have been described as megaprojects. The motives of decision makers for undertaking megaprojects are summarized by Flyvbjerg's (2012, 2014) “four sublimes,” which lack a temporal dimension. We utilize a case study of the 1966 FIFA World Cup in England, applying the three levels of project management identified by Morris and Geraldi (2011), refined through Flyvbjerg's four sublimes, to analyze the shifting nature of stakeholders’ motives. We evidence that Flyvbjerg's sublimes are dynamic in response to change during the project timeline, creating new insights into project development and opportunities for research into historic projects.
Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies

Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed.
Exact Calculation of Integrated Prediction Variance for Response Surface Designs on Cuboidal and Spherical Regions

Over the years, design optimality evaluation of response surface designs focused mainly on D-optimality and G-optimality criteria. The apparent limited use of the IV-optimality criterion appears to be influenced by the computational challenges associated with the criterion. The lack of available computer code appears to be the main reason for limited use of the IV-optimality criterion. In addition, the IV-optimality criterion appears more difficult to code than the D-optimality criterion because of the integration required over the specified design region. In this paper, an efficient and exact method is presented for computing the IV-optimality criterion for selected response surface designs. The pseudo-code for the computer program is also presented. The investigation examines both spherical and cuboidal regions of interest. In addition, an analytical approach is outlined for computing the IV-optimality criterion for second-order split-plot designs. A particular feature of the analytical expressions is that they are derived using the design parameters. In addition, several comparisons of second-order response surface designs are illustrated for completely randomized designs and split-plot designs.
Use of diffusion tensor imaging as a prognostic biomarker after decompression surgery for carpal tunnel syndrome

Background Magnetic resonance diffusion tensor imaging (MR-DTI) has been increasingly applied for carpal tunnel syndrome (CTS) diagnosis, but relatively little is known about the effect of CTS treatment on median nerve (MN) integrity and functional outcome prediction. Purpose To assess how structural changes in MR-DTI of the MN correlates with symptom severity, functional status, and electrophysiological parameters in patients suffering from CTS before and after decompression surgery. Material and Methods Nine wrists were prospectively enrolled to perform MR-DTI pre- and postoperatively. The apparent diffusion coefficients (ADC) and fractional anisotropy (FA) of the MN were examined in three different regions—distal radioulnar joint, pisiform bone, and hamate bone—and correlated with clinical and electrophysiological parameters. Results Postoperatively, mean Boston Carpal Tunnel Questionnaire scores decreased 1.55 points (range = 0.08–3; P = 0.0172) and 1.01 points (−0.13 to 1.88; P = 0.0381) in the symptomatic and functional domains, respectively. Postoperative clinical improvement was reflected in proximal FA elevation (P = 0.0078), but not in diffusivity in comparison to baseline examination. Preoperative electrophysiological parameters were correlated with a reduction in the pre- (sensory latencies [rho = –0.6826; P = 0.0312]) and postoperative (motor latencies [rho = –0.7488; P = 0.0325]) distal FA values. Higher sensory amplitudes indicated higher postoperative proximal FA values (rho = 0.7618; P = 0.0280) and lower postoperative proximal ADC values (rho = –0.9047; P = 0.0020). Conclusion Our study demonstrated that pre- and postoperative proximal FA values are useful biomarkers for the structural evaluation of the MN in patients with CTS. Symptomatic improvement can be better predicted by analyzing FA changes.
Circulating sestrins and force velocity profiling in older adults with type 2 diabetes

ABSTRACT Type 2 diabetes mellitus (T2DM) in old age affects the musculoskeletal system causing loss of muscle mass, strength, and physical function. Stress-inducible proteins named sestrins are potential novel biomarkers of muscle function due to their ability to suppress oxidative stress and prevent muscle degeneration. Our aim was to determine the association between different force-velocity (F-V) profiles with body composition, physical performance, and glucose control in older adults with T2DM. We also intended to determine the potential utility of sestrin 1 (Sesn1) and 2 (Sesn2) as biomarkers of physical functionality. Fifty-nine participants (69–79 years) were classified in 3 groups according to their F-V profile based on the leg press exercise: nondeficit (NDEF = 40.7%), force deficit (FDEF = 28.8%), and velocity deficit (VDEF = 30.5%). Both VDEF and FDEF groups showed lower muscle power than NDEF (Cohen’s d 0.87 and 0.75 for effect size, respectively). Serum Sesn2 levels, maximal dynamic strength, arms and legs fat-free mass were reduced in FDEF compared to the NDEF group (p < 0.05), whereas glycated haemoglobin (HbA1c) and fasting glucose levels were similar among groups. ROC analysis revealed the distinction between the NDEF and FDEF group based on Sesn2 concentrations (<0.72 ng/mL), suggesting their potential use as functional biomarkers for early intervention through exercise. Older adults with T2DM show different F-V profiles, related to low levels of Sesn2, impaired body composition and physical performance, and may be taken into consideration to target exercise training in this specific population. Highlights The influence of different F-V deficit profiles on body composition, physical function and circulating sestrins in older adults with type 2 diabetes were studied. Both force and velocity deficits negatively affected muscle power. Force deficits are associated to low circulating sestrin 2 levels and regional fat-free mass. Basal serum sestrin 2 levels are potential biomarkers to characterise F-V profiles.
Effect of Intravenous Alteplase Treatment on First-Line Stent Retriever Versus Aspiration Alone During Endovascular Treatment

Background: We aimed to assess whether the effect of intravenous alteplase treatment (IVT) before endovascular treatment (EVT) on outcome is modified by first-line technique during EVT in IVT eligible patients. Methods: This was a post hoc analysis from MR CLEAN-NO IV (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands - Intravenous Treatment Followed by Intra-Arterial Treatment Versus Direct Intra-Arterial Treatment for Acute Ischemic Stroke Caused by a Proximal Intracranial Occlusion), a randomized trial of IVT followed by EVT versus EVT alone in patients presenting directly to EVT-capable centers. We included data from all patients who underwent EVT with a thrombectomy attempt. We compared patients treated with stent retriever (with or without aspiration) to aspiration alone as first-line EVT technique and assessed the interaction of first-line EVT technique with IVT treatment. Primary outcome was the 90-day modified Rankin Scale score, analyzed with mixed model ordinal regression for a shift towards better outcome. Secondary outcomes included successful reperfusion (extended Thrombolysis in Cerebral Infarction score 2b–3). Results: Of 473 included patients, 102 (21.6%) were treated with aspiration alone as first-line technique. In the full population, functional outcome was similar for patients treated with stent retriever versus aspiration only (adjusted common odds ratio [acOR]‚ 1.07 [95% CI, 0.69–1.66]). We observed a significant interaction between IVT and first-line EVT technique (P=0.03). In the aspiration-only group, patients treated with EVT alone had worse functional outcome compared to those treated with IVT and EVT (acOR, 0.44 [95% CI, 0.21–0.90]). In the stent retriever group, functional outcome did not differ between patients treated with or without IVT (acOR, 1.08 [95% CI, 0.74–1.57]). There was no statistically significant interaction for successful reperfusion. Conclusions: In MR CLEAN-NO IV, the treatment effect of IVT was modified by first-line EVT technique. Patients treated with aspiration only as first-line technique had worse clinical outcomes if they did not receive IVT. No such difference was observed in patients treated with stent retrievers. Confirmation by pooling with results from other trials is needed to confirm these findings.
Anti-TSH receptor antibodies (TRAb): Comparison of two third generation automated immunoassays broadly used in clinical laboratories and results interpretation

Graves’ disease (GD) is the most common cause of hyperthyroidism in iodine-replete populations. It is an autoimmune disease caused by autoantibodies to the TSHR (TRAb). Although the diagnostic is mainly clinical, measuring TRAb improves accuracy and provides valuable prognostic information. The aim of this study was to compare the performance of two of the most widely used immunoassays i.e., EliA™ anti-TSH-R and Elecsys® anti-TSH-R. We have carried out a comparative study measuring TRAb by the two immunoassays in consecutive sera samples referred to the laboratory for TRAb measurement. Autoantibodies were measured in all samples in parallel by the two techniques. The two techniques were highly concordant as demonstrated by a Cohen’s kappa of 0.82. At the manufacturer recommended cut-off, sensitivity of Elecsys® TRAb test was higher (100% vs. 96.6%), while specificity of the EliA™ TRAb test was higher (99.4% vs. 95.3%). In most patients TRAb are detected by any of two tests which are both well suited for Clinical Laboratories use. However, a higher specificity may constitute an advantage for measurement used not for screening but for diagnostic purposes, as anti-TSH-R is.
Electronic recording of lifetime locomotory activity patterns of adult medflies

Age-specific and diurnal patterns of locomotory activity, can be considered as biomarkers of aging in model organisms and vary across the lifetime of individuals. Τhe Mediterranean fruit fly (medfly), Ceratitis capitata, is a commonly used model-species in studies regarding demography and aging. In the present study, we introduce a modification of the automated locomotory activity electronic device LAM25system (Locomotory Activity Monitor)–Trikinetics, commonly used in short time studies, to record the daily locomotory activity patterns of adult medflies throughout the life. Additionally, fecundity rates and survival of adult medflies were recorded. Male and female medflies were kept in the system tubes and had access to an agar-based gel diet, which provided water and nutrients. The locomotory activity was recorded at every minute by three monitors in the electronic device. The locomotory activity of females was higher than that of males across the different ages. For both sexes locomotory rates were high during the first 20 days of the adult life and decreased in older ages. The activity of males was high in the morning and late afternoon hours, while that of females was constantly high throughout the photophase. Negligible locomotory activity was recorded for both sexes during the nighttime. Males outlived females. Fecundity of females was higher in younger ages. Our results support the adoption of LAM25system in studies addressing aging of insects using medfly as a model organism.
Epidemiology and genetic characterization of human metapneumovirus in pediatric patients from Hangzhou China

Human metapneumovirus (HMPV), which is distributed worldwide, is a significant viral respiratory pathogen responsible for causing acute respiratory tract infections (ARTIs) in children. The aim of the present study was to investigate the epidemiological and genetic characteristics of HMPV in pediatric patients in Hangzhou China following the peak of onset of coronavirus disease 2019 (COVID‐19). A total of 1442 throat swabs were collected from the pediatric patients with a diagnosis of ARTI from November 2020 to March 2021. The following viruses were detected by real‐time polymerase chain reaction analysis: HMPV, RSV, adenovirus, hPIV1‐3, influenza A, and influenza B. A two‐step method was used to amplify the F genes of the HMPV‐positive samples. Following sequencing, phylogenetic analyses were conducted using the MEGA version 7 software package. Among the 1442 samples, 103 (7.14%) were positive for HMPV. No significant differences were observed in the gender distribution. The highest incidence of HMPV occurred in children older than 6 years and the lowest was noted in children younger than 6 months. Lower respiratory tract infections were diagnosed at a higher rate than upper respiratory tract infections in HMPV‐infected children. Only 10 HMPV‐infected children (5.41%) were inpatients compared with 93 outpatients (7.39%). Co‐infection was observed in 31 HMPV‐positive samples including 24 samples of double infection and seven samples of triple infection. A total of 61F gene fragments of HMPV, which were approximately 727 bp in length were successfully sequenced. All the HMPVs belonged to the genotype B and were clustered into subgenotypes B1 (1.6%, 1/61) and B2 (98.4%, 60/61). A total of four specific amino acid substitutions were noted as follows: aa280, aa296, aa392, and aa396. These substitutions were present between sequences derived from the subgenotypes B1 and B2 in the fusion open reading frame from position 244 to 429. In conclusion, the present study provided significant information regarding the epidemiological and genetic characteristics of HMPV in children living in Hangzhou. Following the first peak of the COVID‐19 pandemic, HMPV was considered an important viral respiratory pathogen present in children with ARTI.
An Engineered λ Phage Enables Enhanced and Strain-Specific Killing of Enterohemorrhagic Escherichia coli

Pathogenic strains of Escherichia coli are responsible for 0.8 million deaths per year and together ranked the first among all pathogenic species. Here, we obtained, for the first time, an engineered phage, Eλ, that could specifically and efficiently eliminate EHEC, one of the most common and often lethal pathogens that can spread from person to person. ABSTRACT Bacteriophages (phages) are ideal alternatives to traditional antimicrobial agents in a world where antimicrobial resistance (AMR) is emerging and spreading at an unprecedented speed. In addition, due to their narrow host ranges, phages are also ideal tools to modulate the gut microbiota in which alterations of specific bacterial strains underlie human diseases, while dysbiosis caused by broad-spectrum antibiotics can be harmful. Here, we engineered a lambda phage (Eλ) to target enterohemorrhagic Escherichia coli (EHEC) that causes a severe, sometimes lethal intestinal infection in humans. We enhanced the killing ability of the Eλ phage by incorporating a CRISPR-Cas3 system into the wild-type λ (wtλ) and the specificity by introducing multiple EHEC-targeting CRISPR spacers while knocking out the lytic gene cro. In vitro experiments showed that the Eλ suppressed the growth of EHEC up to 18 h compared with only 6 h with the wtλ; at the multiplicity of infection (MOI) of 10, the Eλ killed the EHEC cells with ~100% efficiency and did not affect the growth of other laboratory- and human-gut isolated E. coli strains. In addition, the EHEC cells did not develop resistance to the Eλ. Mouse experiments further confirmed the enhanced and strain-specific killing of the Eλ to EHEC, while the overall mouse gut microbiota was not disturbed. Our methods can be used to target other genes that are responsible for antibiotic resistance genes and/or human toxins, engineer other phages, and support in vivo application of the engineered phages. IMPORTANCE Pathogenic strains of Escherichia coli are responsible for 0.8 million deaths per year and together ranked the first among all pathogenic species. Here, we obtained, for the first time, an engineered phage, Eλ, that could specifically and efficiently eliminate EHEC, one of the most common and often lethal pathogens that can spread from person to person. We verified the superior performance of the Eλ over the wild-type phage with in vitro and in vivo experiments and showed that the Eλ could suppress EHEC growth to nondetectable levels, fully rescue the EHEC-infected mice, and rescore disturbed mouse gut microbiota. Our results also indicated that the EHEC did not develop resistance to the Eλ, which has been the biggest challenge in phage therapy. We believe our methods can be used to target other pathogenic strains of E. coli and support in vivo application of the engineered phages.