Miracle-dz/UniFAR-FTUs huggingface dataset:
High-resolution three-dimensional blood flow tomography in the subdiffuse regime using laser speckle contrast imaging

Abstract Significance: Visualizing high-resolution hemodynamics in cerebral tissue over a large field of view (FOV), provides important information in studying disease states affecting the brain. Current state-of-the-art optical blood flow imaging techniques either lack spatial resolution or are too slow to provide high temporal resolution reconstruction of flow map over a large FOV. Aim: We present a high spatial resolution computational optical imaging technique based on principles of laser speckle contrast imaging (LSCI) for reconstructing the blood flow maps in complex tissue over a large FOV provided that the three-dimensional (3D) vascular structure is known or assumed. Approach: Our proposed method uses a perturbation Monte Carlo simulation of the high-resolution 3D geometry for both accurately deriving the speckle contrast forward model and calculating the Jacobian matrix used in our reconstruction algorithm to achieve high resolution. Given the convex nature of our highly nonlinear problem, we implemented a mini-batch gradient descent with an adaptive learning rate optimization method to iteratively reconstruct the blood flow map. Specifically, we implemented advanced optimization techniques combined with efficient parallelization and vectorization of the forward and derivative calculations to make reconstruction of the blood flow map feasible with reconstruction times on the order of tens of minutes. Results: We tested our reconstruction algorithm through simulation of both a flow phantom model as well as an anatomically correct murine cerebral tissue and vasculature captured via two-photon microscopy. Additionally, we performed a noise study, examining the robustness of our inverse model in presence of 0.1% and 1% additive noise. In all cases, the blood flow reconstruction error was <2 % for most of the vasculature, except for the peripheral vasculature which suffered from insufficient photon sampling. Descending vasculature and deeper structures showed slightly higher sensitivity to noise compared with vasculature with a horizontal orientation at the more superficial layers. Our results show high-resolution reconstruction of the blood flow map in tissue down to 500 μm and beyond. Conclusions: We have demonstrated a high-resolution computational imaging technique for visualizing blood flow map in complex tissue over a large FOV. Once a high-resolution structural image is captured, our reconstruction algorithm only requires a few LSCI images captured through a camera to reconstruct the blood flow map computationally at a high resolution. We note that the combination of high temporal and spatial resolution of our reconstruction algorithm makes the solution well-suited for applications involving fast monitoring of flow dynamics over a large FOV, such as in functional neural imaging.
Synaptic Variability and Cortical Gamma Oscillation Power in Schizophrenia.

OBJECTIVE Cognitive impairments in schizophrenia are associated with lower gamma oscillation power in the prefrontal cortex (PFC). Gamma power depends in part on excitatory drive to fast-spiking parvalbumin interneurons (PVIs). Excitatory drive to cortical neurons varies in strength, which could affect how these neurons regulate network oscillations. The authors investigated whether variability in excitatory synaptic strength across PVIs could contribute to lower prefrontal gamma power in schizophrenia. METHODS In postmortem PFC from 20 matched pairs of comparison and schizophrenia subjects, levels of vesicular glutamate transporter 1 (VGlut1) and postsynaptic density 95 (PSD95) proteins were quantified to assess variability in excitatory synaptic strength across PVIs. A computational model network was then used to simulate how variability in excitatory synaptic strength across fast-spiking (a defining feature of PVIs) interneurons (FSIs) regulates gamma power. RESULTS The variability of VGlut1 and PSD95 levels at excitatory inputs across PVIs was larger in schizophrenia relative to comparison subjects. This alteration was not influenced by schizophrenia-associated comorbid factors, was not present in monkeys chronically exposed to antipsychotic medications, and was not present in calretinin interneurons. In the model network, variability in excitatory synaptic strength across FSIs regulated gamma power by affecting network synchrony. Finally, greater synaptic variability interacted synergistically with other synaptic alterations in schizophrenia (i.e., fewer excitatory inputs to FSIs and lower inhibitory strength from FSIs) to robustly reduce gamma power. CONCLUSIONS The study findings suggest that greater variability in excitatory synaptic strength across PVIs, in combination with other modest synaptic alterations in these neurons, can markedly lower PFC gamma power in schizophrenia.
Precision medicine in pancreatic cancer: Patient derived organoid pharmacotyping is a predictive biomarker of clinical treatment response.

RATIONALE Patient-derived organoids (PDOs) are a promising technology to support precision medicine initiatives for patients with pancreatic ductal adenocarcinoma (PDAC). PDOs may improve clinical next-generation sequencing (NGS) and enable rapid ex vivo chemotherapeutic screening (pharmacotyping). METHODS PDOs were derived from tissues obtained during surgical resection and endoscopic biopsies and studied with NGS and pharmacotyping. PDO-specific pharmacotype is assessed prospectively as a predictive biomarker of clinical therapeutic response by leveraging data from a randomized-controlled clinical trial. RESULTS Clinical sequencing pipelines often fail to detect PDAC-associated somatic mutations in surgical specimens that demonstrate a good pathological response to previously administered chemotherapy. Sequencing the PDOs derived from these surgical specimens, after biomass expansion, improves the detection of somatic mutations and enables quantification of copy number variants. The detection of clinically relevant mutations and structural variants is improved following PDO biomass expansion. On clinical trial, PDOs were derived from biopsies of treatment naïve patients prior to treatment with FOLFIRINOX (FFX). Ex vivo PDO pharmacotyping with FFX components predicted clinical therapeutic response in these patients with borderline resectable or locally advanced PDAC treated in a neoadjuvant or induction paradigm. PDO pharmacotypes suggesting sensitivity to FFX components were associated with longitudinal declines of tumor marker, CA-19-9 and favorable RECIST imaging response. CONCLUSION PDOs establishment from tissues obtained from patients previously receiving cytotoxic chemotherapies can be accomplished in a clinically-certified laboratory. Sequencing PDOs following biomass expansion improves clinical sequencing quality. High in-vitro sensitivity to standard-of-care chemotherapeutics predicts good clinical response to systemic chemotherapy in PDAC.
Mucoadhesive Nucleoside-Based Hydrogel Delays Oral Leukoplakia Canceration

Some oral squamous cell carcinomas (OSCCs) originate from preexisting oral potentially malignant disorders (OPMDs). Oral leukoplakia (OLK) is the most common and typical OPMD in the clinic, so treatment for it is essential to reduce OSCC incidence. Local chemotherapy is an option other than surgery considering the superficial site of OLK. However, there are no standardized drugs applied to OLK, and traditionally used chemotherapeutic drugs revealed limited efficacy for lack of adhesion. Hence, there is a growing demand to prepare new agents that combine mucoadhesion with an anti-OLK effect. Here, an isoguanosine–tannic acid (isoG-TA) supramolecular hydrogel via dynamic borate esters was successfully fabricated based on isoG and TA. Previously reported guanosine-TA (G-TA) hydrogel was also explored for an anti-OLK effect. Both gels not only exhibited ideal adhesive properties but also integrated anti-OLK activities in one system. In vitro cell viability indicated that isoG and TA inhibited the proliferation of dysplastic oral keratinocytes (DOKs). The in vivo OLK model evidence revealed that both gels showed potential to prevent OLK canceration. In addition, the probable anti-DOK mechanisms of isoG and TA were investigated. The results indicated that isoG could bind to adenosine kinase (ADK) and then affected the mammalian target of rapamycin (mTOR) pathway to inhibit DOK proliferation. TA could significantly and continuously reduce reactive oxygen species (ROS) in DOKs through its antioxidant effect. ROS plays an important role in the progression of cell cycle. We proved that the low level of ROS may inhibit DOK proliferation by inducing G0/G1 arrest in the cell cycle. Altogether, this study innovatively fabricated an isoG-TA hydrogel with ideal adhesion, and both isoG and TA showed in vitro inhibition of DOKs. Moreover, both isoG-TA and G-TA hydrogels possessed potential in delaying the malignant transformation of OLK, and the G-TA hydrogel showed a better statistical effect, providing an effective strategy for controlling OLK.
EEG Spectral Power Analysis: A Comparison Between Heroin Dependent and Control Groups

Previous studies indicated that heroin abuse would result in abnormal functional organization of the brain. However, studies of heroin abuse- related brain dysfunction are scarce. The purpose of the present study was to investigate heroin effects on brain function by studying relationships between Electroencephalograph (EEG) spectral power and heroin abuse. The resting EEG signals were acquired from 15 male heroin dependent group and 15 male control group. The differences in the EEG components of each group were evaluated using the statistical Mann-Whitney examination and Davis Bouldin Index. The results show that heroin dependent group has an attenuated relative beta-2 power compared with other EEG frequency sub bands. Nevertheless, the results indicate heroin dependent group have an increase of power spectrum density for theta at all locations, as well as delta in the temporal, frontal and central areas compared with control group. Compared to control group, the heroin dependent group decreased its spectral power more than the control group in all three alpha bands. The present findings using the Davis Bouldin Index provide evidence that alpha-3 band in the FZ channel is more affected by heroin abuse than other frequency sub bands.
Oblique lateral interbody fusion combined with lateral plate fixation for the treatment of degenerative diseases of the lumbar spine

Abstract Oblique lateral interbody fusion (OLIF) is a minimally invasive decompression technique used in the treatment of lumbar degenerative diseases (LDDs). It is usually combined with posterior pedicle screw fixation to decrease perioperative complications. Few studies have reported the efficacy of OLIF combined with lateral plate instrumentation (OLIF-LP) for the treatment of LDDs. The purpose of this retrospective study was to evaluate the clinical efficacy of OLIF combined with lateral plate instrumentation for the treatment of LDDs. From May 2020 to September 2020, the clinical data of 52 patients who underwent OLIF-LP were analyzed. The operation time, blood loss, and complications were recorded. The radiological parameters, visual analog scale score, and Oswestry Disability Index were evaluated. The average operation time, blood loss, and length of hospital stay were 75.41 ± 11.53 minutes, 39.57 ± 9.22 mL, and 7.22 ± 1.85 days, respectively. The visual analog scale score and Oswestry Disability Index both improved significantly after surgery (7.23 ± 1.26 vs 2.15 ± 0.87; 60.27 ± 7.91 vs 21.80 ± 6.32, P < .01). The postoperative disk height was 13.02 ± 8.83 mm, which was much greater than the preoperative value. The postoperative foraminal height improved significantly (16.18 ± 3.49 vs 21.54 ± 2.12 mm, P < .01), and the cross-sectional area improved from 88.95 ± 14.79 to 126.53 ± 8.83 mm2 (P < .001). The radiological fusion rate was 88% at the last follow-up. No major complications, such as ureteral injury, vascular injury, or vertebral body fracture, occurred. Use of the OLIF-LP technique can help avoid lumbar posterior surgery and minimize the operative time and blood loss. OLIF-LP can achieve 1-stage intervertebral fusion and instrumentation through a single small incision.
TBK1 is Required for Host Defense Functions Distinct from Type I IFN Expression and Myeloid Cell Recruitment in Murine S. pneumoniae pneumonia.

Bacterial pneumonia induces the rapid recruitment and activation of neutrophils and macrophages into the lung, and these cells contribute to bacterial clearance and other defense functions. TANK-binding kinase 1 (TBK1) performs many functions including activation of the type I interferon (IFN) pathway and regulation of autophagy and mitophagy, but its contribution to antibacterial defenses in the lung is unclear. We previously showed that lung neutrophils upregulate mRNAs for TBK1 and its accessory proteins during S. pneumoniae pneumonia, despite low or absent expression of type I IFN in these cells. We hypothesized that TBK1 performs key antibacterial functions in pneumonia apart from type I IFN expression. Using TBK1 null mice, we show that TBK1 contributes to anti-bacterial defenses and promotes bacterial clearance and survival. TBK1 null mice express lower levels of many cytokines in the infected lung. Conditional deletion of TBK1 with LysMCre results in TBK1 deletion from macrophages but not neutrophils. LysMCre TBK1 mice have no defect in cytokine expression, implicating a non-macrophage cell type as a key TBK1-dependent cell. TBK1 null neutrophils have no defect in recruitment to the infected lung but show impaired activation of p65/NF-κB and STAT1 and lower expression of ROS, IFNγ, and IL12p40. TLR1/2 and 4 agonists each induce phosphorylation of TBK1 in neutrophils. Surprisingly, neutrophil TBK1 activation in vivo does not require the adaptor STING. Thus, TBK1 is a critical component of STING-independent antibacterial responses in the lung, and TBK1 is necessary for multiple neutrophil functions.
Weight gain during pregnancy and placenta morphology: a prospective cohort study.

OBJECTIVE The aim of this study was to assess the association between maternal weight gain and placenta morphology in the complete placenta previa pregnancies. PATIENTS AND METHODS This was a prospective clinical cohort study. Pregnancy weight gain was defined as the difference between delivery and at first trimester. Morphological parameters, including placenta length, breadth, thickness, length-breadth, surface area, weight, and fetoplacental weight ratio, were direct measured delivery. RESULTS Eighty-five women were included in this study. Maternal weight gain was 11.12 ± 3.95 kg. Placenta length, breadth, thickness, length-breadth, surface area, weight and fetoplacental weight ratio were 19.42 ± 1.97 cm, 18.29 ± 1.80 cm, 2.18 ± 0.38 cm, 1.13 ± 0.80 cm, 281.60 ± 57.23 cm2, 569.05 ± 118.77 g, and 4.88 ± 0.88, respectively. Correlation analysis showed that there was a positive correlation between maternal weight gain and placenta length (r = 0.261, p = 0.016), placenta breadth (r = 0.239, p = 0.028), and placenta surface area (r = 0.254, p = 0.019). In the linear regression model, maternal weight gain was significantly associated with placenta length [β (95% CI): 0.130 (0.025-0.236)], breadth [β (95% CI): 0.109 (0.012-0.205)], and surface area [β (95%CI): 3.677 (0.615-6.739)]. The results were still stable after adjusting for pre-pregnancy weight. CONCLUSIONS Maternal weight gain in pregnancy was associated with placental length, placental breadth, and placental surface area in a complete placenta previa pregnancies. Considering the single center data, further studies are needed to recognize the significance of the association analyzed in our study.
Linking ecological niche models and common garden experiments to predict phenotypic differentiation in stressful environments: Assessing the adaptive value of marginal populations in an alpine plant

Environmental variation within a species’ range can create contrasting selective pressures, leading to divergent selection and novel adaptations. The conservation value of populations inhabiting environmentally marginal areas remains in debate and is closely related to the adaptive potential in changing environments. Strong selection caused by stressful conditions may generate novel adaptations, conferring these populations distinct evolutionary potential and high conservation value under climate change. On the other hand, environmentally marginal populations may be genetically depauperate, with little potential for new adaptations to emerge. Here, we explored the use of ecological niche models (ENMs) linked with common garden experiments to predict and test for genetically determined phenotypic differentiation related to contrasting environmental conditions. To do so, we built an ENM for the alpine plant Silene ciliata in central Spain and conducted common garden experiments, assessing flowering phenology changes and differences in leaf cell resistance to extreme temperatures. The suitability patterns and response curves of the ENM led to the predictions that: (1) the environmentally marginal populations experiencing less snowpack and higher minimum temperatures would have delayed flowering to avoid risks of late‐spring frosts and (2) those with higher minimum temperatures and greater potential evapotranspiration would show enhanced cell resistance to high temperatures to deal with physiological stress related to desiccation and heat. The common garden experiments revealed the expected genetically based phenotypic differentiation in flowering phenology. In contrast, they did not show the expected differentiation for cell resistance, but these latter experiments had high variance and hence lower statistical power. The results highlight ENMs as useful tools to identify contrasting putative selective pressures across species ranges. Linking ENMs with common garden experiments provides a theoretically justified and practical way to study adaptive processes, including insights regarding the conservation value of populations inhabiting environmentally marginal areas under ongoing climate change.
Linking lifestyle and foraging strategies of marine bacteria: selfish behaviour of particle‐attached bacteria in the northern Adriatic Sea

Summary Microbe‐mediated enzymatic hydrolysis of organic matter entails the production of hydrolysate, the recovery of which may be more or less efficient. The selfish uptake mechanism, recently discovered, allows microbes to hydrolyze polysaccharides and take up large oligomers, which are then degraded in the periplasmic space. By minimizing the hydrolysate loss, selfish behaviour may be profitable for free‐living cells dwelling in a patchy substrate landscape. However, selfish uptake seems to be tailored to algal‐derived polysaccharides, abundant in organic particles, suggesting that particle‐attached microbes may use this strategy. We tracked selfish polysaccharides uptake in surface microbial communities of the northeastern Mediterranean Sea, linking the occurrence of this processing mode with microbial lifestyle. Additionally, we set up fluorescently labelled polysaccharides incubations supplying phytodetritus to investigate a ‘pioneer’ scenario for particle‐attached microbes. Under both conditions, selfish behaviour was almost exclusively carried out by particle‐attached microbes, suggesting that this mechanism may represent an advantage in the race for particle exploitation. Our findings shed light on the selfish potential of particle‐attached microbes, suggesting multifaceted foraging strategies exerted by particle colonizers.
An Assessment of the Economic Potential of Offshore Wind in the United States from 2015 to 2030

Output data from an NREL report entitled "An Assessment of the Economic Potential of Offshore Wind in the United States from 2015 to 2030" (NREL/TP-6A20-67675), which analyzes the spatial variation of levelized cost of energy (LCOE) and levelized avoided cost of energy (LACE) to understand the economic potential of fixed-bottom and floating offshore wind technologies across more than 7,000 U.S. coastal sites between 2015 and 2030.
Analysis of Prognostic Risk Factors for Ischemic Stroke in China: A Multicentre Retrospective Clinical Study; A National Survey in China

Background: Stroke is a serious disease that threatens human health both in China and worldwide. Identifying and establishing its risk factors are prerequisites for intervention and evaluation of prognosis. Over the years, risk factors, such as age, diabetes, and hypertension, have gradually been established. However, at present, there is no consensus on the influence of sex on the prognosis of ischaemic stroke. Aims: The aims of our research was to analyse the correlation between sex and poststroke prognosis based on the results of the Third China National Stroke Registry [CNSR-III], as well as the influence of other risk factors that may be confounded by sex on ischaemic stroke and potential interventions. Methods: The CNSR-III recruited 14146 acute ischaemic stroke [AIS] patients between 2015 and 2018. Our study included 13,972 patients who had complete follow-up information. This research analysed basic information, socioeconomic status, lifestyle habits, medical history, and poststroke prognosis. Results: There was a conspicuous relationship between sex and functional prognosis, stroke recurrence and all-cause death due to ischemic stroke in univariate analysis. Male stroke patients had a better prognosis than female patients. In multivariate analysis, we found that age, atrial fibrillation [AF], diabetes, hypertension and the severity of stroke had adverse effects on ischemic stroke prognosis. After adjustment for other risk factors, the functional prognosis of female patients at 3 months was worse than that of male patients [odds ratio [OR] 1.16, 95% confidence interval [CI], 1.025-1.314]. Sex had a nonsignificant association with stroke recurrence at 3 months [hazard ratio [HR] 1.141, 95% CI, 0.975-1.336]. Furthermore, compared to male patients, female stroke patients had a lower cumulative death rate at 12 months [HR 0.777, 95% CI, 0.628-0.963]. Conclusion: Our study identified sex differences in stroke-related disability, recurrence, and death and attempted to explain the causes of these differences. Our study clearly showed that a large proportion of this difference could be attributed to age, socioeconomic factors, lifestyle habits, and medical history, confounded by sex differences rather than sex per se.