Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of Immortalized Human Tumor Endothelial Cells from Renal Cancer

Tumor angiogenesis research and antiangiogenic drug development make use of cultured endothelial cells (ECs) including the human microvascular ECs among others. However, it has been reported that tumor ECs (TECs) are different from normal ECs (NECs). To functionally validate antiangiogenic drugs, cultured TECs are indispensable tools, but are not commercially available. Primary human TECs are available only in small quantities from surgical specimens and have a short life span in vitro due to their cellular senescence. We established immortalized human TECs (h-imTECs) and their normal counterparts (h-imNECs) by infection with lentivirus producing simian virus 40 large T antigen and human telomerase reverse transcriptase to overcome the replication barriers. These ECs exhibited an extended life span and retained their characteristic endothelial morphology, expression of endothelial marker, and ability of tube formation. Furthermore, h-imTECs showed their specific characteristics as TECs, such as increased proliferation and upregulation of TEC markers. Treatment with bevacizumab, an antiangiogenic drug, dramatically decreased h-imTEC survival, whereas the same treatment failed to alter immortalized NEC survival. Hence, these h-imTECs could be a valuable tool for drug screening to develop novel therapeutic agents specific to TECs or functional biological assays in tumor angiogenesis research.
The Association of Obstructive Sleep Apnea Syndrome and Accident Risk in Heavy Equipment Operators

Background and Objectives: Obstructive sleep apnea syndrome (OSAS) is the most frequent sleep disorder, characterized by the repeated collapse of the upper respiratory tract during sleep. In this study, we aimed to determine the prevalence of OSAS in heavy equipment operators and to determine the relationship between the work accidents that these operators were involved in and the OSAS symptoms and severity. In doing this, we aimed to emphasize the association of OSAS, which is a treatable disease, and these accidents, which cause loss of manpower, financial hampering, and even death. Materials and Methods: STOP BANG questionnaire was provided to 965 heavy equipment operators and polysomnography (PSG) was performed, in Izmir Esrefpasa Municipality Hospital, to the operators at high risk for OSAS. Demographic data, health status, and accidents of these operators were recorded. Results: All operators who participated in the study were male. The ages of the cases ranged from 35 to 58 and the mean age was 45.07 ± 5.54 years. The mean STOP BANG questionnaire results were 4.36 ± 3.82. In total, 142 operators were identified with high risk for OSAS and PSG could be performed on 110 of these 142 operators. According to the PSG results of the operators, 41 (37.3%) patients had normal findings, while 35 (31.8%) had mild, 20 (18.2%) had moderate, and 14 (12.7%) had severe OSAS. Among those 110 patients, 71 (64.5%) of the cases had no history of any accidents, 25 (22.8%) were almost involved in an accident due to sleepiness, and 14 (12.7%) were actually involved in an accident. There was a statistically significant relationship between the accident rate and OSAS severity (p: 0.009). Conclusion: Based on the data acquired in the present study, a positive correlation was determined between the accident statuses of drivers with OSAS severity. We want to attract attention to the necessity of evaluating the OSAS symptoms in professional heavy equipment operators during the certification period and at various intervals afterwards, and to carry out OSAS evaluations by PSG for those having a certain risk.
Functional Reorganization of Local Circuit Connectivity in Superficial Spinal Dorsal Horn with Neuropathic Pain States

Abstract The spinal dorsal horn is the first relay structure coding for pain transmission and modulation. Previous anatomical and electrophysiological studies have examined spinal dorsal horn circuit connections and network activity. Further work is required to understand spinal cord sensory information processing that underlies pathological neuropathic pain states. Our previous studies suggest that peripheral nerve injury enhances presynaptic excitatory input onto spinal superficial dorsal horn neurons, which in turn contributes to pathologic nociception. The potential changes in local postsynaptic circuits in the dorsal horn that lead to pathologically heightened behavioral responses to pain remain largely unexplored. We combined whole-cell electrophysiological recordings with laser-scanning photostimulation to test whether peripheral nerve injury in the spinal nerve ligation (SNL) mouse model of neuropathic pain leads to alterations in the functional connectivity of spinal cord circuits including lamina II excitatory interneurons. Here we show that SNL enhances excitation and decreases inhibition to lamina II excitatory interneurons along with their increased glutamate-evoked excitability. The enhanced excitatory postsynaptic input and connectivity evoked by SNL eventually return to normal levels concurrently with the resolution of the neuropathic pain states. The physiological pattern highly correlates with mouse pain behaviors following SNL, supporting a neurophysiological mechanism of central sensitization and neuropathic pain that is functionally localized to the spinal dorsal horn. Together, these data support that SNL induces functional changes in synaptic input and connectivity to lamina II excitatory interneurons that code for pain perception, and thus provide new insights into the mechanism and locus of pain hypersensitivity.
Evaluation of the acute and 28-day sub-acute intravenous toxicity of α-l-guluronic acid (ALG; G2013) in mice

Abstract α-l-Guluronic acid (ALG; G2013) has been previously introduced as a new anti-inflammatory agent with promising therapeutic effects. Thus, in the present study, we aimed to evaluate the acute and sub-acute toxicity of ALG through intravenous (i.v.) administration in Balb/C mice. ALG was administrated i.v. to the mice with doses of 300, 600, and 1000 mg/kg of body weight to investigate acute toxicity (single dose) and with doses of 25, 50, and 100 mg/kg of body weight to sub-acute toxicity study (daily injections for a period of 28 days). The mortality rate, food and water intake, behavior, body weight, gross necropsy, hematological and biochemical parameters as well as histopathological presentations of the vital organs (kidneys, liver, lungs, spleen, and heart) were examined in treated groups and compared to the healthy controls. The results of both acute and sub-acute studies showed that i.v. administrations of ALG did not affect the investigated parameters in both sexes, indicating that the LD50 of ALG was higher than 1000 mg/kg of body weight. As no difference was observed in toxicity profiles of investigated doses, no-observed-adverse-effect-level for i.v. administration of ALG in the sub-acute study was greater than 100 mg/kg body weight in both female and male mice. According to the finding, i.v. administration of ALG did not lead to any clinical sign in abovementioned doses, suggesting that ALG was well tolerated up to 1000 mg/kg. These pre-clinical findings support the application of ALG in the future clinical trials.
Endothelial β-Catenin Signaling Supports Postnatal Brain and Retinal Angiogenesis by Promoting Sprouting, Tip Cell Formation, and VEGFR (Vascular Endothelial Growth Factor Receptor) 2 Expression.

OBJECTIVE Activation of endothelial β-catenin signaling by neural cell-derived Norrin or Wnt ligands is vital for the vascularization of the retina and brain. Mutations in members of the Norrin/β-catenin pathway contribute to inherited blinding disorders because of defective vascular development and dysfunctional blood-retina barrier. Despite a vital role for endothelial β-catenin signaling in central nervous system health and disease, its contribution to central nervous system angiogenesis and its interactions with downstream signaling cascades remains incompletely understood. Approach and Results: Here, using genetically modified mouse models, we show that impaired endothelial β-catenin signaling caused hypovascularization of the postnatal retina and brain because of deficient endothelial cell proliferation and sprouting. Mosaic genetic analysis demonstrated that endothelial β-catenin promotes but is not required for tip cell formation. In addition, pharmacological treatment revealed that angiogenesis under conditions of inhibited Notch signaling depends upon endothelial β-catenin. Importantly, impaired endothelial β-catenin signaling abrogated the expression of the VEGFR (vascular endothelial growth factor receptor)-2 and VEGFR3 in brain microvessels but not in the lung endothelium. CONCLUSIONS Our study identifies molecular crosstalk between the Wnt/β-catenin and the Notch and VEGF-A signaling pathways and strongly suggest that endothelial β-catenin signaling supports central nervous system angiogenesis by promoting endothelial cell sprouting, tip cell formation, and VEGF-A/VEGFR2 signaling.
Notification of relapse and other previously treated tuberculosis in the 52 health districts of South Africa.

OBJECTIVE: To investigate the extent to which relapse and other previously treated tuberculosis (TB) contribute to the notified TB burden in South Africa.DESIGN: We conducted an ecological analysis at the level of the 52 South African health districts using national electronic TB register data. We included all bacteriologically confirmed TB cases treated for presumed drug-susceptible TB in 2011. Treatment history information was based on recorded patient categories (new vs. retreatment). RESULTS: Relapse and other previously treated TB cases constituted between 7.6% and 40% (median 17%, interquartile range 12-22) of all bacteriologically confirmed TB cases in the 52 South African districts. Multivariable analysis suggested that districts with higher proportions of previously treated TB cases had higher TB case notification rates (P < 0.001), lower estimates of antenatal human immunodeficiency virus (HIV) prevalence in the district population (P < 0.001) as well as lower HIV co-infection rates (P < 0.001) among new TB cases.CONCLUSION: Relapse and other previously treated TB cases contributed substantially to the notified TB burden in several South African health districts, particularly those with high case notification rates and lower antenatal HIV prevalence. Additional efforts to prevent TB among previously treated people, such as strengthening treatment monitoring and/or secondary preventive therapy, should be considered.
Mosquito-Specific Viruses—Transmission and Interaction

Mosquito-specific viruses (MSVs) are a subset of insect-specific viruses that are found to infect mosquitoes or mosquito derived cells. There has been an increase in discoveries of novel MSVs in recent years. This has expanded our understanding of viral diversity and evolution but has also sparked questions concerning the transmission of these viruses and interactions with their hosts and its microbiome. In fact, there is already evidence that MSVs interact with the immune system of their host. This is especially interesting, since mosquitoes can be infected with both MSVs and arthropod-borne (arbo) viruses of public health concern. In this review, we give an update on the different MSVs discovered so far and describe current data on their transmission and interaction with the mosquito immune system as well as the effect MSVs could have on an arboviruses-co-infection. Lastly, we discuss potential uses of these viruses, including vector and transmission control.
Learning Nonclassical Receptive Field Modulation for Contour Detection

This work develops a biologically inspired neural network for contour detection in natural images by combining the nonclassical receptive field modulation mechanism with a deep learning framework. The input image is first convolved with the local feature detectors to produce the classical receptive field responses, and then a corresponding modulatory kernel is constructed for each feature map to model the nonclassical receptive field modulation behaviors. The modulatory effects can activate a larger cortical area and thus allow cortical neurons to integrate a broader range of visual information to recognize complex cases. Additionally, to characterize spatial structures at various scales, a multiresolution technique is used to represent visual field information from fine to coarse. Different scale responses are combined to estimate the contour probability. Our method achieves state-of-the-art results among all biologically inspired contour detection models. This study provides a method for improving visual modeling of contour detection and inspires new ideas for integrating more brain cognitive mechanisms into deep neural networks.
Engagement and Short-term Abstinence Outcomes among Blacks and Whites in the National Cancer Institute's SmokefreeTXT Program.

INTRODUCTION Text-messaging programs for smoking cessation improve abstinence outcomes in the general population. However, little is known about engagement and abstinence outcomes among African Americans in text-messaging smoking cessation programs. The current study compares engagement and abstinence between Blacks and Whites in the National Cancer Institute's SmokefreeTXT program. METHOD Data were from Blacks (n = 1,333) and Whites (n =7,154) who enrolled in the 6-week SmokefreeTXT program between August 2017 and June 2018. We assessed the association between race and program initiation and completion; responses to weekly smoking cessation, mood, and craving assessments; and self-reported abstinence using multivariable logistic regression. RESULTS Blacks and Whites initiated the program at a similar frequency, yet Blacks were more likely to complete the program (adjusted odds ratio [AOR] = 1.71, 95% CI = 1.43 to 2.06). Blacks were less likely to respond to all seven abstinence, mood, and craving assessments (e.g., AOR of quit day responses = 0.63, 95% CI =0.51 to 0.77; 6-week AOR = 0.50, 95% CI = 0.34 to 0.72). Self-reported abstinence was lower among Blacks for all seven smoking assessments (e.g., quit day abstinence AOR = 0.52, 95% CI =0.41 to 0.68; 6-week abstinence AOR = 0.58, 95% CI = 0.38 to 0.89). CONCLUSION Although Blacks were more likely than Whites to complete the SmokefreeTXT program, they were less likely to engage with the program by responding to assessment questions and had lower abstinence rates. Qualitative research may reveal unique barriers to engagement among Blacks. IMPLICATIONS Black smokers enrolled in a nationwide mobile smoking cessation program at a rate comparable to White smokers. However, they were significantly less likely to engage with the program or quit smoking. This study highlights the need to examine barriers to cessation for Black smokers.
Reactive Oxygen Species and Obstructive Lung Disease 73

The respiratory system is constantly exposed to both endogenous and exogenous oxidants. Oxidative stress plays a critical role in the development, progression, monitoring, and, perhaps in the future, the treatment of both asthma and chronic obstructive pulmonary disease. It is estimated that asthma currently affects 300 million people globally, with its prevalence increasing by 50 % every decade.
Kinetochore-mediated outward force promotes spindle pole separation in fission yeast

Bipolar spindles are organized by motor proteins that generate microtubule-dependent forces to separate the two spindle poles. The fission yeast Cut7 (kinesin-5) is a plus-end-directed motor that generates the outward force to separate the two spindle poles, whereas the minus-end-directed motor Pkl1 (kinesin-14) generates the inward force. Balanced forces by these antagonizing kinesins are essential for bipolar spindle organization in mitosis. Here, we demonstrate that chromosomes generate another outward force that contributes to the bipolar spindle assembly. First, it was noted that the cut7 pkl1 double knockout failed to separate spindle poles in meiosis I, although the mutant is known to succeed it in mitosis. It was assumed that this might be because meiotic kinetochores of bivalent chromosomes joined by cross-overs generate weaker tensions in meiosis I than the strong tensions in mitosis generated by tightly tethered sister kinetochores. In line with this idea, when meiotic mono-oriented kinetochores were artificially converted to a mitotic bioriented layout, the cut7 pkl1 mutant successfully separated spindle poles in meiosis I. Therefore, we propose that spindle pole separation is promoted by outward forces transmitted from kinetochores to spindle poles through microtubules.
Perceptual Evaluation for Multi-Exposure Image Fusion of Dynamic Scenes

A common approach to high dynamic range (HDR) imaging is to capture multiple images of different exposures followed by multi-exposure image fusion (MEF) in either radiance or intensity domain. A predominant problem of this approach is the introduction of the ghosting artifacts in dynamic scenes with camera and object motion. While many MEF methods (often referred to as deghosting algorithms) have been proposed for reduced ghosting artifacts and improved visual quality, little work has been dedicated to perceptual evaluation of their deghosting results. Here we first construct a database that contains 20 multi-exposure sequences of dynamic scenes and their corresponding fused images by nine MEF algorithms. We then carry out a subjective experiment to evaluate fused image quality, and find that none of existing objective quality models for MEF provides accurate quality predictions. Motivated by this, we develop an objective quality model for MEF of dynamic scenes. Specifically, we divide the test image into static and dynamic regions, measure structural similarity between the image and the corresponding sequence in the two regions separately, and combine quality measurements of the two regions into an overall quality score. Experimental results show that the proposed method significantly outperforms the state-of-the-art. In addition, we demonstrate the promise of the proposed model in parameter tuning of MEF methods. The subjective database and the MATLAB code of the proposed model are made publicly available at https://github.com/h4nwei/MEF-SSIMd.
Mir-152 Regulates 3T3-L1 Preadipocyte Proliferation and Differentiation

Adipogenesis is a complex biological process and the main cause of obesity. Recently, microRNAs (miRNAs), a class of small endogenous non-coding RNAs, have been proven to play an important role in adipogenesis by the post-transcriptional regulation of target genes. In this current study, we observed an increment of miR-152 expression during the process of 3T3-L1 cell audiogenic differentiation. A functional analysis indicated that the overexpression of miR-152 inhibited pre-adipocyte proliferation and suppressed the expression of some cell cycle-related genes. Moreover, the overexpression of miR-152 promoted lipid accumulation in 3T3-L1 preadipocytes accompanied by increase of the expression of some pro-audiogenic genes. Additionally, a dual-luciferase reporter assay demonstrated lipoprotein lipase (LPL) was a direct target gene of miR-152 during preadipocyte differentiation. Further analysis showed that miR-152 was positively correlated with adipogenesis and intramuscular fat formation in vivo. Taken together, our findings suggest that miR-152 could suppress 3T3-L1 preadipocyte proliferation, whereas it could promote 3T3-L1 preadipocyte differentiation by negatively regulating LPL. The findings indicate that miR-152 might have a therapeutic significance for obesity and obesity-related metabolic syndrome.
Adaptive viral load monitoring frequency to facilitate differentiated care: a modeling study from Rakai, Uganda.

INTRODUCTION After scaleup of antiretroviral therapy (ART), routine annual viral load monitoring has been adopted by most countries, but reduced frequency of viral load monitoring may offer cost savings in resource limited settings. We investigated if viral load monitoring frequency could be reduced while maintaining detection of treatment failure. METHODS The Rakai Health Sciences Program performed routine, biannual viral load monitoring on 2,489 HIV infected persons (age 15+). Based on these data, we built a two-stage simulation model to compare different viral load monitoring schemes. We fit Weibull regression models for time to viral load above 1000 copies/ml (treatment failure), and simulated data for 10,000 individuals over 5 years to compare five monitoring schemes to the current viral load testing every six months and testing every 12 months. RESULTS Among seven monitoring schemes tested, monitoring every six months for all subjects had the fewest months of undetected failure but also had the highest number of viral load tests. Adaptive schemes using previous viral load measurements to inform future monitoring significantly decreased the number of viral load tests without markedly increasing the number of months of undetected failure. The best adaptive monitoring scheme resulted in a 67% reduction in viral load measurements, while increasing the months of undetected failure by <20%. CONCLUSIONS Adaptive viral load monitoring based on previous viral load measurements may be optimal for maintaining patient care while reducing costs, allowing more patients to be treated and monitored. Future empirical studies to evaluate differentiated monitoring are warranted.
Peri‐operative considerations for sedation‐analgesia during cataract surgery: a narrative review

Cataract surgery is usually of short duration and is associated with minimal pain when employing topical or regional anaesthesia. Patient education regarding the peri‐operative process may help alleviate anxiety and avoid the need for sedation. However, sedation may be required, and we discuss the various options. Many consider that pre‐operative fasting is necessary due to the risk of aspiration but fasting may not be required if minimal sedation is administered. If the use of sedatives, hypnotics or analgesics is required, then their associated adverse events should be considered.
Praktisches Vorgehen bei Erstdiagnose einer Leberzirrhose

Liver cirrhosis is a major healthcare problem and is associated with an increased mortality due to the development of complications. Therefore, after diagnosis of liver cirrhosis, it is highly clinically relevant to evaluate the reason for liver cirrhosis and to assess the presence of complications in order to prevent progression of liver cirrhosis.
The evolving role of radiotherapy in non-small cell lung cancer

Lung cancer is the most commonly diagnosed cancer and biggest cause of cancer mortality worldwide with non-small cell lung cancer (NSCLC) accounting for most cases. Radiotherapy (RT) plays a key role in its management and is used at least once in over half of patients in both curative and palliative treatments. This narrative review will demonstrate how the evolution of RT for NSCLC has been underpinned by improvements in RT technology. These improvements have facilitated geometric individualization, increasingly accurate treatment and now offer the ability to deliver truly individualized RT. In this review, we summarize and discuss recent developments in the field of advanced RT in early stage, locally advanced and metastatic NSCLC. We highlight limitations in current approaches and discuss future potential treatment strategies for patients with NSCLC.
Handbook for death scene investigators

Guidelines for the Investigator Signs of Sudden Death and Disease at the Scene Obtaining Medical History Traumatic Deaths Time of Death and Decomposition Decedent Identification Scene Evidence Collection Signs of CPR and Treatment The Autopsy Other Experts Cause, Manner, and Mechanism Appendices Medical Terminology Prescription Medications Photographs Index