Miracle-dz/UniFAR-FTUs huggingface dataset:
Botulinum Toxin Effects on Sensorimotor Integration in Focal Dystonias

(1) Background: In dystonia, the somatosensory temporal discrimination threshold (STDT) is abnormally increased at rest and higher and longer-lasting during movement execution in comparison with healthy subjects (HS), suggesting an abnormal sensorimotor integration. These abnormalities are thought to depend on abnormal proprioceptive input coming from dystonic muscles. Since Botulinum toxin-A (BT-A) reduces proprioceptive input in the injected muscles, our study investigated the effects of BT-A on STDT tested at rest and during voluntary movement execution in patients with focal dystonia. (2) Methods: We enrolled 35 patients with focal dystonia: 14 patients with cervical dystonia (CD), 11 patients with blepharospasm (BSP), and 10 patients with focal hand dystonia (FHD); and 12 age-matched HS. STDT tested by delivering paired stimuli was measured in all subjects at rest and during index finger abductions. (3) Results: Patients with dystonia had higher STDT values at rest and during movement execution than HS. While BT-A did not modify STDT at rest, it reduced the abnormal values of STDT during movement in CD and FHD patients, but not in BSP patients. (4) Conclusions: BT-A improved abnormal sensorimotor integration in CD and FHD, most likely by decreasing the overflow of proprioceptive signaling from muscle dystonic activity to the thalamus.
Predictive Maintenance for Pump Systems and Thermal Power Plants: State-of-the-Art Review, Trends and Challenges

Thermal power plants are an important asset in the current energy infrastructure, delivering ancillary services, power, and heat to their respective consumers. Faults on critical components, such as large pumping systems, can lead to material damage and opportunity losses. Pumps plays an essential role in various industries and as such clever maintenance can ensure cost reductions and high availability. Prognostics and Health Management, PHM, is the study utilizing data to estimate the current and future conditions of a system. Within the field of PHM, Predictive Maintenance, PdM, has been gaining increased attention. Data-driven models can be built to estimate the remaining-useful-lifetime of complex systems that would be difficult to identify by man. With the increased attention that the Predictive Maintenance field is receiving, review papers become increasingly important to understand what research has been conducted and what challenges need to be addressed. This paper does so by initially conceptualising the PdM field. A structured overview of literature in regard to application within PdM is presented, before delving into the domain of thermal power plants and pump systems. Finally, related challenges and trends will be outlined. This paper finds that a large number of experimental data-driven models have been successfully deployed, but the PdM field would benefit from more industrial case studies. Furthermore, investigations into the scale-ability of models would benefit industries that are looking into large-scale implementations. Here, examining a method for automatic maintenance of the developed model will be of interest. This paper can be used to understand the PdM field as a broad concept but does also provide a niche understanding of the domain in focus.
Cerebrospinal Fluid YKL-40 and Chitotriosidase Levels in Frontotemporal Dementia Vary by Clinical, Genetic and Pathological Subtype

Background: Chronic glial dysfunction may contribute to the pathogenesis of frontotemporal dementia (FTD). Cerebrospinal fluid (CSF) levels of glia-derived proteins YKL-40 and chitotriosidase are increased in Alzheimer’s disease (AD) but have not been explored in detail across the spectrum of FTD. Methods: We investigated whether CSF YKL-40 and chitotriosidase levels differed between FTD patients and controls, across different clinical and genetic subtypes of FTD, and between individuals with a clinical FTD syndrome due to AD versus non-AD (frontotemporal lobar degeneration, FTLD) pathology (based on CSF neurodegenerative biomarkers). Eighteen healthy controls and 64 people with FTD (behavioural variant FTD, n = 20; primary progressive aphasia [PPA], n = 44: nfvPPA, n = 16, svPPA, n = 11, lvPPA, n = 14, PPA-NOS, n = 3) were included. 10/64 had familial FTD, with mutations in GRN(n = 3), MAPT(n = 4), or C9orf72 (n = 3). 15/64 had neurodegenerative biomarkers consistent with AD pathology. Levels were measured by immunoassay and compared using multiple linear regressions. We also examined relationships of YKL-40 and chitotriosidase with CSF total tau (T-tau), phosphorylated tau 181 (P-tau) and β-amyloid 1–42 (Aβ42), with each other, and with age and disease duration. Results: CSF YKL-40 and chitotriosidase levels were higher in FTD, particularly lvPPA (both) and nfvPPA (YKL-40), compared with controls. GRN mutation carriers had higher levels of both proteins than controls and C9orf72 expansion carriers, and YKL-40 was higher in MAPT mutation carriers than controls. Individuals with underlying AD pathology had higher YKL-40 and chitotriosidase levels than both controls and those with likely FTLD pathology. CSF YKL-40 and chitotriosidase levels were variably associated with levels of T-tau, P-tau and Aβ42, and with each other, depending on clinical syndrome and underlying pathology. CSF YKL-40 but not chitotriosidase was associated with age, but not disease duration. Conclusion: CSF YKL-40 and chitotriosidase levels are increased in individuals with clinical FTD syndromes, particularly due to AD pathology. In a preliminary analysis of genetic groups, levels of both proteins are found to be highly elevated in FTD due to GRN mutations, while YKL-40 is increased in individuals with MAPT mutations. As glia-derived protein levels generally correlate with T-tau and P-tau levels, they may reflect the glial response to neurodegeneration in FTLD.
Multi-level feature aggregation network for instrument identification of endoscopic images

Identification of surgical instruments is crucial in understanding surgical scenarios and providing an assistive process in endoscopic image-guided surgery. This study proposes a novel multilevel feature-aggregated deep convolutional neural network (MLFA-Net) for identifying surgical instruments in endoscopic images. First, a global feature augmentation layer is created on the top layer of the backbone to improve the localization ability of object identification by boosting the high-level semantic information to the feature flow network. Second, a modified interaction path of cross-channel features is proposed to increase the nonlinear combination of features in the same level and improve the efficiency of information propagation. Third, a multiview fusion branch of features is built to aggregate the location-sensitive information of the same level in different views, increase the information diversity of features, and enhance the localization ability of objects. By utilizing the latent information, the proposed network of multilevel feature aggregation can accomplish multitask instrument identification with a single network. Three tasks are handled by the proposed network, including object detection, which classifies the type of instrument and locates its border; mask segmentation, which detects the instrument shape; and pose estimation, which detects the keypoint of instrument parts. The experiments are performed on laparoscopic images from MICCAI 2017 Endoscopic Vision Challenge, and the mean average precision (AP) and average recall (AR) are utilized to quantify the segmentation and pose estimation results. For the bounding box regression, the AP and AR are 79.1% and 63.2%, respectively, while the AP and AR of mask segmentation are 78.1% and 62.1%, and the AP and AR of the pose estimation achieve 67.1% and 55.7%, respectively. The experiments demonstrate that our method efficiently improves the recognition accuracy of the instrument in endoscopic images, and outperforms the other state-of-the-art methods.
Membrane Phospholipids and Polyphosphates as Cofactors and Binding Molecules of SERPINA12 (vaspin)

Visceral adipose tissue derived serine protease inhibitor (vaspin) is a member of the serpin family and has been shown to have beneficial effects on glucose tolerance, insulin stability as well as adipose tissue inflammation, parameters seriously affected by obesity. Some of these effects require inhibition of target proteases such as kallikrein 7(KLK7) and many studies have demonstrated vaspin-mediated activation of intracellular signaling cascades in various cells and tissues. So far, little is known about the exact mechanism how vaspin may trigger these intracellular signaling events. In this study, we investigated and characterized the interaction of vaspin with membrane lipids and polyphosphates as well as their potential regulatory effects on serpin activity using recombinant vaspin and KLK7 proteins and functional protein variants thereof. Here, we show for the first time that vaspin binds to phospholipids and polyphosphates with varying effects on KLK7 inhibition. Vaspin binds strongly to monophosphorylated phosphatidylinositol phosphates (PtdInsP) with no effect on vaspin activation. Microscale thermophoresis (MST) measurements revealed high-affinity binding to polyphosphate 45 (KD: 466 ± 75 nM) and activation of vaspin in a heparin-like manner. Furthermore, we identified additional residues in the heparin binding site in β-sheet A by mutating five basic residues resulting in complete loss of high-affinity heparin binding. Finally, using lipid overlay assays, we show that these residues are additionally involved in PtdInsP binding. Phospholipids play a major role in membrane trafficking and signaling whereas polyphosphates are procoagulant and proinflammatory agents. The identification of phospholipids and polyphosphates as binding partners of vaspin will contribute to the understanding of vaspins involvement in membrane trafficking, signaling and beneficial effects associated with obesity.
Standardizing Discrete Time Hazard Ratios with a Disease Risk Score.

The disease risk score (DRS) can be used to summarize a potentially large vector of covariates with a single variable. The DRS can be used to control for confounding by the covariates that went into estimation of the DRS and obtain a standardized estimate of an exposure's effect on disease. However, to-date, literature on the DRS has not addressed analyses that focus on estimation of survival or hazard functions, which are common in epidemiological analyses of cohort data. Here, we propose a method for standardization of hazard ratios using the DRS in longitudinal analyses of the association between a binary exposure and outcome. This approach to handling a potentially large set of covariates through a model-based approach to standardization may provide a useful tool for cohort analyses of hazard ratios, and may particularly well-suited to settings where an exposure propensity score is difficult to model. Simulations are used to illustrate the approach, and an empirical example is provided.
A rapid intrinsic heart rate resetting response with thermal acclimation in rainbow trout, Oncorhynchus mykiss

ABSTRACT We examined cardiac pacemaker rate resetting in rainbow trout following a reciprocal temperature transfer. In the original experiment, performed in winter, 4°C-acclimated fish transferred to 12°C reset intrinsic heart rate after just 1 h (from 56.8±1.2 to 50.8±1.5 beats min−1); 12°C-acclimated fish transferred to 4°C reset intrinsic heart rate after 8 h (from 33.4±0.7 to 37.7±1.2 beats min−1). However, in a replicate experiment, performed in the summer using a different brood year, intrinsic heart rate was not reset, even after 10 weeks at a new temperature. Using this serendipitous opportunity, we compared mRNA expression changes of a suite of proteins in sinoatrial node (SAN), atrial and ventricular tissues after both 1 h and longer than 3 weeks for both experimental acclimation groups to identify those changes only associated with pacemaker rate resetting. Of the changes in mRNA expression occurring after more than 3 weeks of warm acclimation and associated with pacemaker rate resetting, we observed downregulation of NKA α1c in the atrium and ventricle, and upregulation of HCN1 in the ventricle. However, in the SAN there were no mRNA expression changes unique to the fish with pacemaker rate resetting after either 1 h or 3 weeks of warm acclimation. Thus, despite identifying changes in mRNA expression of contractile cardiac tissues, there was an absence of changes in mRNA expression directly involved with the initial, rapid pacemaker rate resetting with warm acclimation. Importantly, pacemaker rate resetting with thermal acclimation does not always occur in rainbow trout. Summary: Intrinsic heart rate resetting occurs inconsistently with temperature acclimation in rainbow trout; however, it can occur rapidly, within 1 h of warming, without changes in mRNA expression of sinoatrial node proteins.
Esophageal Pressure Versus Gas Exchange to Set PEEP During Intraoperative Ventilation

BACKGROUND: Pneumoperitoneum and Trendelenburg position affect respiratory system mechanics and oxygenation during elective pelvic robotic surgery. The primary aim of this randomized pilot study was to compare the effects of a conventional low tidal volume ventilation with PEEP guided by gas exchange (VGas-guided) versus low tidal volume ventilation tailoring PEEP according to esophageal pressure (VPes-guided) on oxygenation and respiratory mechanics during elective pelvic robotic surgery. METHODS: This study was conducted in a single-center tertiary hospital between September 2017 and January 2019. Forty-nine adult patients scheduled for elective pelvic robotic surgery were screened; 28 subjects completed the full analysis. Exclusion criteria were American Society of Anesthesiologists physical status ≥ 3, contraindications to nasogastric catheter placement, and pregnancy. After dedicated naso/orogastric catheter insertion, subjects were randomly assigned to VGas-guided (FIO2 and PEEP set to achieve SpO2 > 94%) or VPes-guided (PEEP tailored to equalize end-expiratory transpulmonary pressure). Oxygenation (PaO2/FIO2) was evaluated (1) at randomization, after pneumoperitoneum and Trendelenburg application; (2) at 60 min; (3) at 120 min following randomization; and (4) at end of surgery. Respiratory mechanics were assessed during the duration of the study. RESULTS: Compared to VGas-guided, oxygenation was higher with VPes-guided at 60 min (388 ± 90 vs 308 ± 95 mm Hg, P = .02), at 120 min after randomization (400 ± 90 vs 308 ± 81 mm Hg, P = .008), and at the end of surgery (402 ± 95 vs 312 ± 95 mm Hg, P = .009). Respiratory system elastance was lower with VPes-guided compared to VGas-guided at 20 min (24.2 ± 7.3 vs 33.4 ± 10.7 cm H2O/L, P = .001) and 60 min (24.1 ± 5.4 vs 31.9 ± 8.5 cm H2O/L, P = .006) from randomization. CONCLUSIONS: Oxygenation and respiratory system mechanics were improved when applying a ventilatory strategy tailoring PEEP to equalize expiratory transpulmonary pressure in subjects undergoing pelvic robotic surgery compared to a VGas-guided approach. (ClinicalTrials.gov registration NCT03153592).
Intracranial Pressure in Traumatic Brain Injury: From Thresholds to Heuristics.

Intracranial pressure (ICP) remains the most central monitoring variable in severe traumatic brain injury (TBI). Explanations for ICP’s hegemony include the following: a) refractory intracranial hypertension (IHT) is a precursor of brain herniation and cerebral circulatory arrest; b) IHT has been consistently associated with mortality in observational cohorts; c) measuring and monitoring ICP is relatively uncomplicated when compared with detecting other mechanisms leading to secondary brain injury (SBI); and d) provides the means for estimating cerebral perfusion pressure (CPP). Using ICP/CPP as targets is the recommended strategy by both the Brain Trauma Foundation (BTF) guidelines (1), and expert consensus (2), and a leading way of practicing (at least in highincome countries) (3). Inherent to these recommendations are the tactics of escalating tiers of management according to threshold values of ICP and CPP (4). The BTF recommends treating ICP above 22 mm Hg because epidemiologic values above this level have been associated with increased mortality (5) (level IIB recommendation) and to include clinical and radiographic data in management decisions (level III). This generic-threshold treatment paradigm is criticized for a number of reasons including methodologic issues in deriving thresholds, pathophysiologic reasons, and lack of high-level clinical outcome evidence (Table 1 provides an exegesis of criticisms). Notwithstanding objections, one should keep in mind that implementation of the BTF guidelines has been associated with a reduction in mortality after TBI (6) (remains unknown if this is a protocol effect vs the contribution of individual components); this fact will become further salient below in relation to a “heuristics” understanding. In view of the limitations, what alternative approaches could one entertain? One approach is to abandon ICP monitoring, and with it, ICP threshold–guided management. Such a strategy has been proposed as the Imaging and Clinical Examination protocol (ICE) and has been derived from and tested in the Benchmark Evidence from South American Trials: Treatment of Intracranial Pressure trial (BEST-TRIP) trial against an ICP-monitored control group (7, 8). A detailed exposition is out-of-scope; however, it is helpful to highlight two takeaways. First, the trial was negative in terms of primary clinical outcome, and second, the ICE group required more intensive brain-specific treatment. Another approach, on the opposite spectrum and inspired by multimodality neuromonitoring (MMM), aims to assess cerebrovascular pressure reactivity, brain tissue oxygenation, cerebral metabolism, and energy dynamics (9). The motivation is to remedy a number of the criticisms leveled against the fixed treatment threshold, including management individualization and determinations of optimal CPP (10), or patient-specific critical ICP (11).
Resistance training attenuates circulating FGF-21 and myostatin and improves insulin resistance in elderly men with and without type 2 diabetes mellitus: A randomised controlled clinical trial

Abstract Fibroblast growth factor 21 (FGF-21) and myostatin have been proposed to be potential therapeutic target for insulin resistance in age-related metabolic disorders including type 2 diabetes (T2D). Moreover, despite the potential metabolic effect of resistance training on insulin resistance, aging, and T2D; the effect of this type of exercise training on FGF-21 and myostatin in elderly men with and without T2D are unknown. Forty-four elderly men were assigned to either the RT training (RT; without T2D: 12, with TD2 = 10) or the control group (C; without T2D: 12, with TD2 = 10). The RT group performed 12-wk resistance training intervention, 3 days/wk, 10 repetitions with 70% 1RM. At the baseline, the elderly men with T2D had a higher FGF-21 (p = 0.002) and myostatin (p = 0.02) concentrations and lower muscle strength (p = 0.01) than the elderly men without T2D. RT resulted in significant decrease in FGF-21 and myostatin concentration and increase in muscle strength in both elderly men with and without T2D (P = 0.001, for all) as well as decrease in HOMA-IR in only elderly men without T2D (P = 0.001). There was no significant difference in the RT-induced FGF-21 reduction between elderly men with and without T2D (p = 0.77, p = 0.28, respectively), but, RT caused a larger reduction in circulating myostatin in elderly men without T2D than with T2D (P = 0.007). Taken together, our results demonstrated that 12 weeks of RT induced an overall significant reduction of FGF-21 and myostatin in elderly men with and without T2D; with higher reduction of myostatin in elderly men without T2D.
Identification of Metabolic Alterations in Breast Cancer Using Mass Spectrometry-Based Metabolomic Analysis

Breast cancer (BC) is a major global health issue and remains the second leading cause of cancer-related death in women, contributing to approximately 41,760 deaths annually. BC is caused by a combination of genetic and environmental factors. Although various molecular diagnostic tools have been developed to improve diagnosis of BC in the clinical setting, better detection tools for earlier diagnosis can improve survival rates. Given that altered metabolism is a characteristic feature of BC, we aimed to understand the comparative metabolic differences between BC and healthy controls. Metabolomics, the study of metabolism, can provide incredible insight and create useful tools for identifying potential BC biomarkers. In this study, we applied two analytical mass spectrometry (MS) platforms, including hydrophilic interaction chromatography (HILIC) and gas chromatography (GC), to generate BC-associated metabolic profiles using breast tissue from BC patients. These metabolites were further analyzed to identify differentially expressed metabolites in BC and their associated metabolic networks. Additionally, Chemical Similarity Enrichment Analysis (ChemRICH), MetaMapp, and Metabolite Set Enrichment Analysis (MSEA) identified significantly enriched clusters and networks in BC tissues. Since metabolomic signatures hold significant promise in the clinical setting, more effort should be placed on validating potential BC biomarkers based on identifying altered metabolomes.
Insecticide Responses in the Collembola Pest, Sminthurus viridis (Collembola: Sminthuridae), in Australia

Abstract Lucerne flea (Sminthurus viridis Linnaeus) is an important establishment pest of winter grain crops and pastures in Australia. Control of S. viridis largely relies on the application of insecticides through foliar sprays or seed treatments; however, in recent years, farmers have faced increasing difficulties managing this pest. This is likely due to their high inherent tolerance to certain chemicals, although there are increasing concerns around emerging resistance. Despite this, there have been no studies worldwide investigating insecticide sensitivity shifts on S. viridis. Further, there is currently no established method to test the response of S. viridis to neonicotinoids, which are now widely used to protect many crops attacked by this species. Here, we established a robust and sensitive bioassay methodology to test neonicotinoids against S. viridis. We also generated important sensitivity data for the first time across multiple S. viridis populations from geographically distinct regions in Australia to two commonly used insecticides, omethoate, and imidacloprid. While there was variation in responses between populations for both chemicals, there is no evidence to suggest insecticide resistance has evolved in the field. This study is an important step for future monitoring of insecticide resistance in S. viridis, particularly given the considerable selection pressure imposed on this pest in Australia and its purported high-risk of evolving resistance.