Miracle-dz/UniFAR-FTUs huggingface dataset:
Gut microbiota and fecal metabolic signatures in rat models of disuse-induced osteoporosis

Background Assessing the correlation between gut microbiota (GM) and bone homeostasis has increasingly attracted research interest. Meanwhile, GM dysbiosis has been found to be associated with abnormal bone metabolism. However, the function of GM in disuse-induced osteoporosis (DIO) remains poorly understood. In our research, we evaluated the characteristics of GM and fecal metabolomics to explore their potential correlations with DIO pathogenesis. Methods DIO rat models and controls (CON) underwent micro-CT, histological analyses, and three-point bending tests; subsequently, bone microstructures and strength were observed. ELISAs were applied for the measurement of the biochemical markers of bone turnover while GM abundance was observed using 16S rDNA sequencing. Metabolomic analyses were used to analyze alterations fecal metabolites. The potential correlations between GM, metabolites, and bone loss were then assessed. Results In the DIO group, the abundance of GM was significantly altered compared to that in the CON group. Moreover, DIO significantly altered fecal metabolites. More specifically, an abnormally active pathway associated with bile acid metabolism, as well as differential bacterial genera related to bone/tissue volume (BV/TV), were identified. Lithocholic acid, which is the main secondary bile acid produced by intestinal bacteria, was then found to have a relationship with multiple differential bacterial genera. Alterations in the intestinal flora and metabolites in feces, therefore, may be responsible for DIO-induced bone loss. Conclusions The results indicated that changes in the abundance of GM abundance and fecal metabolites were correlated with DIO-induced bone loss, which might provide new insights into the DIO pathogenesis. The detailed regulatory role of GM and metabolites in DIO-induced bone loss needs to be explored further.
Survival prognostic factors for differentiated thyroid cancer patients with pulmonary metastases: A systematic review and meta-analysis

Background The prognostic factors for differentiated thyroid cancer (DTC) patients with pulmonary metastases (PM) remain scantly identified and analyzed. Therefore, this systematic review and meta-analysis were performed to identify and summarize the prognostic factors in adult DTC patients with PM to help distinguish patients with different prognoses and inform the rational treatment regimens. Method We performed a comprehensive search of the relevant studies published in the Cochrane Library, PubMed, Scopus, Embase, Wanfang database, VIP database, China National Knowledge Infrastructure, and Google Scholar from their inception until February 2021. The pooled hazard ratios (HR) for overall survival and/or progression-free survival (PFS) with 95% confidence intervals were applied to evaluate and identify the potential prognostic factors. Pooled OS at different time points were also calculated for the available data. A random-effects model was used in the meta-analysis. Results The review and meta-analysis included 21 studies comprising 2722 DTC patients with PM. The prognostic factors for poor OS were: age over 40 years (HR=7.21, 95% confidence interval [CI] 1.52-34.10, P=0.01, N=788), age over 45 years (HR=2.18, 95% CI 1.26-3.77, P<0.01, N=601), male gender (HR=1.01, 95% CI 1.01-1.19, P=0.03, N=1396), follicular subtype of thyroid cancer (HR=1.63, 95% CI 1.36-1.96, P<0.01, N=2110), iodine non-avidity (HR=3.10, 95% CI 1.79-5.37, P<0.01, N=646), and metastases to other organs (HR=3.18, 95% CI 2.43-4.16, P<0.01, N=1713). Factors associated with poor PFS included age over 45 years (HR=3.85, 95% CI 1.29-11.47, P<0.01, N=306), male gender (HR=1.36, 95% CI 1.06-1.75, P=0.02, N=546), iodine non-avidity (HR=2.93, 95% CI 2.18-3.95, P<0.01, N=395), pulmonary metastatic nodule size over 10mm (HR=2.56, 95% CI 2.02-3.24, P<0.01, N=513), and extra-thyroidal invasion (HR=2.05, 95% CI 1.15-3.67, P=0.02, N=271). The pooled 1, 3, 5, 10, 15, and 20-years OS were 95.24%, 88.46%, 78.36%, 64.86%, 56.57%, and 51.03%, respectively. Conclusions This review and meta-analysis identified the prognostic factors of DTC patients with PM. Notably, FTC, metastases to other organs, and iodine non-avidity were particularly associated with poor prognosis. The identified prognostic factors will help guide the clinical management of DTC patients with PM. Systematic review registration https://inplasy.com/inplasy-2022-2-0026/, identifier (INPLASY202220026).
A guide for concurrent TMS-fMRI to investigate functional brain networks

Transcranial Magnetic Stimulation (TMS) allows for the direct activation of neurons in the human neocortex and has proven to be fundamental for causal hypothesis testing in cognitive neuroscience. By administering TMS concurrently with functional Magnetic Resonance Imaging (fMRI), the effect of cortical TMS on activity in distant cortical and subcortical structures can be quantified by varying the levels of TMS output intensity. However, TMS generates significant fluctuations in the fMRI time series, and their complex interaction warrants caution before interpreting findings. We present the methodological challenges of concurrent TMS-fMRI and a guide to minimize induced artifacts in experimental design and post-processing. Our study targeted two frontal-striatal circuits: primary motor cortex (M1) projections to the putamen and lateral prefrontal cortex (PFC) projections to the caudate in healthy human participants. We found that TMS parametrically increased the BOLD signal in the targeted region and subcortical projections as a function of stimulation intensity. Together, this work provides practical steps to overcome common challenges with concurrent TMS-fMRI and demonstrates how TMS-fMRI can be used to investigate functional brain networks.
Prefrontal brain function in patients with chronic insomnia disorder: A pilot functional near-infrared spectroscopy study

Purpose Insomnia is one of the most common diseases in elderly patients, which seriously affect the quality of life and psychological state of patients. The purpose of this study was to investigate the changes in the functional network pattern of the prefrontal cortex in patients with chronic insomnia disorder (CID) after taking drugs, using non-invasive and low-cost functional neuroimaging with multi-channel near-infrared spectroscopy (fNIRS). Methods All subjects were assessed using the Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and fNIRS. The fNIRS assessment consists of two parts: the verbal fluency test (VFT) task state and the resting state, which assessed the differences in prefrontal activation and functional connectivity, respectively. Results A total of 30 patients with chronic insomnia disorder (CID) and 15 healthy peers completed the study. During the VFT task, a significantly lower PFC activation was observed in patients with insomnia compared to the control group (P < 0.05). However, the PFC activation in patients taking medication was higher than in patients who did not receive medication. Functional connectivity analysis showed a weaker mean PFC channel connectivity strength in patients with CID who did not receive drug treatment. Drug treatment resulted in enhanced functional connectivity of the prefrontal lobe, especially the DLPFC and frontal poles. Conclusion A weak prefrontal cortex response was detected in patients with CID when performing the VFT task, which could be enhanced by taking hypnotics. The weakened right prefrontal lobe network may play a role in the development of CID. fNIRS may serve as a potential tool to assess sleep status and guide drug therapy.
Alterations of theta power and synchrony during encoding in young adult binge drinkers: Subsequent memory effects associated with retrieval after 48 h and 6 months

Introduction Young emerging adults commonly engage in binge drinking which is associated with a range of neurocognitive deficits, including memory impairments. However, evidence on neural oscillations mediating episodic memory in this population is lacking. To address this gap, we recorded theta oscillatory activity in young binge (BDs) and light drinkers (LDs) during memory encoding and analyzed it prospectively as a function of subsequent retrieval. Theta underlies successful encoding of novel items in memory through corticolimbic integration. Subsequent memory effects (SMEs) are reflected in stronger theta activity during encoding of the items that are later remembered compared to those that are later forgotten. Methods In the present study, 23 BDs (age: 23.3 ± 3.3) and 24 LDs (age: 23.4 ± 3.3) rated emotionally evocative images with negative, positive, and neutral themes during implicit encoding. They performed a recognition memory task on two follow-up occasions after a short (48 h), and long retention delay (6 months). Electroencephalography (EEG) signal was recorded during the encoding session and analyzed in time-frequency domain with Morlet wavelets in theta band (4–7 Hz). To evaluate SMEs, the event-related theta oscillations acquired during encoding were analyzed based on recognition outcomes after the two retention intervals. Results The BD and LD groups did not differ on recognition memory. However, BDs showed attenuated event-related theta power during encoding of images that were successfully retained after 6 months compared to LDs. In addition, theta synchronous activity between frontal and left posterior regions during encoding successfully predicted recognition of the images after both retention delays in LDs but not in BDs. These SMEs on theta power and synchrony correlated negatively with high-intensity drinking in the previous 6 months. No differences between men and women were observed for any analysis. Discussion It has been well established that long-range neural synchrony between cortical and limbic nodes underlies successful memory encoding and retention which, in turn, depends on neural excitation/inhibition (E/I) balance. Given that binge drinking is associated with E/I dysregulation, the observed SME deficiencies are consistent with other evidence of neural hyperexcitability in BDs, and may be indicative of increased risk of developing alcohol use disorders.
Being a team player: Approaching team coordination in sports in dialog with ecological and praxeological approaches

This paper discusses key conceptual resources for an understanding of coordination processes in team sports. It begins by exploring the action guidance provided by the environment, studied in terms of affordances. When conceptualizing sporting performances in general, we might distinguish social and object affordances, think about the spatial and temporal order of affordances in terms of nested and sequential affordances, and differentiate between global, main, and micro-affordances within an action sequence. In the context of team sports, it is crucial to understand how affordances might be given to a plurality of athletes. For that purpose, the paper defines shared, common, and collective affordances. A distinguishing characteristic of team sports is the key role of collaborative intra-team coordination which take place within a setting of antagonistic team-team interactions. A key proposal from dynamical systems theory is to conceptualize intra-team coordination in terms of synergies. Synergies are emergent systems of several athletes who coordinate their movements to achieve specific performance tasks. Many of the embodied skills that players need to develop to become suitable participants in the coordination processes of sport teams are abilities to participate in dynamic sequences of collective activity. Praxeological approaches have emphasized that training processes in team sports are aimed at transforming athletes into skillful participants in sequences of collective play. Athletes need to develop their ability-to-play-with to become proficient in contributing to the formation of suitable collectives for specific performance tasks.
In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways

Regulatory T cells (Tregs) are the master regulators of immunity and they have been implicated in different disease states such as infection, autoimmunity and cancer. Since their discovery, many studies have focused on understanding Treg development, differentiation, and function. While there are many players in the generation and function of truly suppressive Tregs, the role of checkpoint pathways in these processes have been studied extensively. In this paper, we systematically review the role of different checkpoint pathways in Treg homeostasis and function. We describe how co-stimulatory and co-inhibitory pathways modulate Treg homeostasis and function and highlight data from mouse and human studies. Multiple checkpoint pathways are being targeted in cancer and autoimmunity; therefore, we share insights from the clinic and discuss the effect of experimental and approved therapeutics on Treg biology.
PET/CT imaging detects intestinal inflammation in a mouse model of doxorubicin-induced mucositis

Introduction A severe side effect of cancer chemotherapy is the development of gastrointestinal mucositis, characterised by mucosal inflammation. We investigated if 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography combined with computed tomography (2-[18F]FDG-PET/CT) could visualise gastrointestinal mucositis in mice treated with the chemotherapeutic agent doxorubicin. Methods In this study, gastrointestinal inflammation was longitudinally evaluated by 2-[18F]FDG-PET/CT scans before and 1, 3, 6, and 10 days after treatment with doxorubicin. Doxorubicin-treated mice were compared to saline-treated littermates using the abdominal standard uptake value of 2-[18F]FDG corrected for body weight (SUVBW). Results Abdominal SUVBW was significantly increased on day 1 (p < 0.0001), day 3 (p < 0.0001), and day 6 (p < 0.05) in the doxorubicin-treated group compared to controls. Abdominal SUVBW returned to baseline levels on day 10. In the doxorubicin group, the largest weight loss was observed on day 3 (control vs doxorubicin, mean percent of baseline weight: (98.5 ± 3.2% vs 87.9 ± 4.6%, p < 0.0001). Moreover, in the doxorubicin-treated group, villus lengths were decreased by 23-28% on days 1 and 3 in the small intestine (p < 0.05), and jejunal levels of tumour necrosis factor and interleukin-1β were significantly increased on day 3 (p < 0.05). Discussion Together, these findings indicate that sequential 2-[18F]FDG-PET/CT scans can objectively quantify and evaluate the development and resolution of intestinal inflammation over time in a mouse model of doxorubicin-induced mucositis.
Phylogenetic, species richness and logistic influences on the biodiscovery process in Cnidaria

The extent to which any particular taxon supplies novel natural products depends on biological and evolutionary differences, and on decisions made by (or constraints on) biodiscovery scientists. The influences of different sources of variability on the biodiscovery process were examined in a study of the Cnidaria, a group recognised as an important source of novel marine natural products. The number of species with at least one novel metabolite within a genus was related to the number of species in the genus. This pattern implies that different genera do not differ in the probability of containing a species with novel natural products. Outlying points of this relationship were consistent with the ease of obtaining material through culturing organisms. The most productive five species were the sources of over 100 novel metabolites each. The distribution of novel metabolites across species showed no signs of exhausting novelty for the most productive source species. Novel metabolite drug likeness (ADMET-score) varied among genera. However, this pattern of variation was of the same degree as observed for molecular weights of metabolites, suggesting that differences among genera are generated by the decisions of analysts with different interests and do not reflect underlying biology. Biogeographic patterns of soft coral species with novel natural products were matched to regional species richness. Overall, the evidence for phylogenetic or spatial influences on the chance of finding novel metabolites was weak. The patterns are consistent with a constant chance of finding novel natural products across different species, with some constraints linked to ease of sampling or culturing and some reinforcement of biodiscovery in species that have previously been the source of novel metabolites.
Magnetic resonance imaging for characterization of hepatocellular carcinoma metabolism

With a better understanding of the pathophysiological and metabolic changes in hepatocellular carcinoma (HCC), multiparametric and novel functional magnetic resonance (MR) and positron emission tomography (PET) techniques have received wide interest and are increasingly being applied in preclinical and clinical research. These techniques not only allow for non-invasive detection of structural, functional, and metabolic changes in malignant tumor cells but also characterize the tumor microenvironment (TME) and the interactions of malignant tumor cells with the TME, which has hypoxia and low pH, resulting from the Warburg effect and accumulation of metabolites produced by tumor cells and other cellular components. The heterogeneity and complexity of the TME require a combination of images with various parameters and modalities to characterize tumors and guide therapy. This review focuses on the value of multiparametric magnetic resonance imaging and PET/MR in evaluating the structural and functional changes of HCC and in detecting metabolites formed owing to HCC and the TME.
The vulnerability of springs and phreatophyte communities to groundwater level declines in Oregon and Nevada, 2002–2021

Increased groundwater demand is causing aquifer declines that impact viability of groundwater-dependent ecosystems (GDEs) like springs and phreatophyte communities. To understand which springs and phreatophyte communities may be stressed by groundwater level declines in Oregon and Nevada, we assessed groundwater level trends in nearby monitoring wells. Very few springs and phreatophyte communities were near monitoring wells with adequate data. Less than 1% of >50,000 springs in Nevada and Oregon were within 800 m of analyzed wells, and only 52 springs were near a shallow (<30 m below ground surface) well. Among springs near analyzed wells, 56% in Nevada and 29% in Oregon were near wells with declining groundwater level trends, and percentages were similar among springs that were within 800 m of analyzed shallow wells. Less than 22% of all phreatophyte communities in Nevada and Oregon were near analyzed wells, and only 9.6% were within 800 m of a shallow well. Of phreatophyte communities near analyzed wells, 48% and 57% were near wells with declining trends in Nevada and Oregon, respectively. Differences among GDE types could reflect more groundwater development where phreatophytes exist. Differences between states in proportion of springs near wells with declining trends could be due to more surface water capture in Oregon or increased pressure for groundwater development in Nevada. State-specific policies and administration of groundwater rights and monitoring affect data availability and trends observed in the two states. More groundwater level data are essential for understanding impacts of groundwater withdrawals to GDEs.
Diagnostic accuracy of intraoperative brainstem auditory evoked potential for predicting hearing loss after vestibular schwannoma surgery

Objective This meta-analysis evaluated the diagnostic value of intraoperative brainstem auditory evoked potential (BAEP) for predicting post-operative hearing loss. Methods Research articles in MEDLINE, Embase, and Cochrane Library databases were searched and selected up to 20 January 2022, and data were extracted following a standard procedure. A diagnostic accuracy test meta-analysis was performed using a mixed-effect binary regression model. Results A total of 693 patients from 15 studies were extracted. The change in intraoperative BAEP showed high sensitivity (0.95) but low specificity (0.37), with an area under the curve of 0.83. Diagnostic accuracy of the loss of potentials showed high sensitivity (0.82) and specificity (0.79). The area under the curve was 0.88. No factor was found to account for the heterogeneity of the results according to the meta-regression and subgroup analyses (all P-values > 0.05). Conclusions Our results showed that the loss of BAEP has meaningful value for predicting hearing loss after vestibular schwannoma surgery. The change in BAEP is also important for its high sensitivity during hearing preservation surgery.
Glucocorticoid induced adrenal insufficiency in children: Morning cortisol values to avoid LDSST

Objectives Glucocorticoid-induced adrenal insufficiency (GI-AI) is a common side effect of glucocorticoid therapy. However, its diagnosis currently relies on the realization of a Low Dose Short Synacthen Test (LD-SST) that requires an outpatient hospital and several blood samples. Our goal was to evaluate whether morning cortisol values could predict the response to LD-SST, in children, to avoid useless dynamic tests and facilitate diagnosis of glucocorticoid induced adrenal insufficiency. Study Design We recorded data of 91 pediatric patients who underwent a LD-SST in our center between 2016 and 2020 in a retrospective observational study. We selected LD-SST realized following administration of supra-physiologic doses of glucocorticoids during more than 3 weeks and performed at least four weeks after treatment was stopped. Adrenal deficiency was defined as a plasma cortisol concentration inferior to 500 nmol/l at LD-SST. Results Glucocorticoid-induced adrenal insufficiency was diagnosed in 60% of our cohort. Morning cortisol values were predictive of the response to the LD-SST (AUC ROC 0.78). A plasma cortisol concentration of less than 144 nmol/l predicted glucocorticoid induced adrenal insufficiency with a specificity of 94% and a value over 317 nmol/l predicted recovery of the HPA axis with a sensitivity of 95%. We did not find any other predictive factor for glucocorticoid-induced adrenal insufficiency. Conclusions Morning cortisol values can safely assess recovery of the HPA axis in children treated chronically with glucocorticoids. Using these thresholds, more than 50% of LD-SST could be avoided in children.