Miracle-dz/UniFAR-FTUs huggingface dataset:
ProjectAlign: a real-time ultrasound guidance system for spinal midline detection during epidural needle placement

Ultrasound can provide useful guidance for needle insertion in epidural anesthesia, but image interpretation can be challenging. The aim of this work is to determine the feasibility of a new ultrasound-based system (ProjectAlign) capable of identifying the spinal midline directly at the puncture site. ProjectAlign’s main benefit is that it requires no operator interpretation of ultrasound images. Instead, the operator is guided by automatic real-time estimates of spinal midline position projected onto the skin. A simple cross-correlation routine generates increasingly accurate estimates of midline location as the transducer is centred over the spine. A clinical feasibility study was performed to assess the performance of ProjectAlign in identifying the midline in the L2 to L4 lumbar region of 12 subjects. We hypothesized that (i) ProjectAlign can identify the spinal midline within a 5 mm lateral distance of a sonographer’s manual marking, and (ii) ProjectAlign is more laterally accurate than palpation in identifying the spinal midline. Both hypotheses were validated by the data. Midline measurement with ProjectAlign generated an RMS error of 2.0 mm, with a maximum error of 5.0 mm. The results of this study support further investigation into the use of ProjectAlign, in particular for obese patients where palpation is most difficult.
Survivin knockdown induces senescence in TTF-1-expressing, KRAS-mutant lung adenocarcinomas

Survivin plays a key role in regulating the cell cycle and apoptosis, and is highly expressed in the majority of malignant tumors. However, little is known about the roles of survivin in KRAS-mutant lung adenocarcinomas. In the present study, we examined 28 KRAS-mutant lung adenocarcinoma tissues and two KRAS-mutant lung adenocarcinoma cell lines, H358 and H441, in order to elucidate the potential of survivin as a therapeutic target. We found that 19 (68%) of the 28 KRAS-mutant lung adenocarcinomas were differentiated tumors expressing thyroid transcription factor-1 (TTF-1) and E-cadherin. Patients with tumors immunohistochemically positive for survivin (n=18) had poorer outcomes than those with survivin-negative tumors (n=10). In the H358 and H441 cells, which expressed TTF-1 and E-cadherin, survivin knockdown alone induced senescence, not apoptosis. However, in monolayer culture, the H358 cells and H441 cells in which survivin was silenced, underwent significant apoptosis following combined treatment with ABT-263, a Bcl-2 inhibitor, and trametinib, a MEK inhibitor. Importantly, the triple combination of survivin knockdown with ABT-263 and trametinib treatment, clearly induced cell death in a three-dimensional cell culture model and in an in vivo tumor xenograft model. We also observed that the growth of the H358 and H441 cells was slightly, yet significantly suppressed in vitro when TTF-1 was silenced. These findings collectively suggest that the triple combination of survivin knockdown with ABT-263 and trametinib treatment, may be a potential strategy for the treatment of KRAS-mutant lung adenocarcinoma. Furthermore, our findings indicate that the well-differentiated type of KRAS-mutant lung tumors depends, at least in part, on TTF-1 for growth.
The effect of combination therapy of insulin glargine, metformin, and sitagliptin on insulin secretion, insulin resistance, and metabolic parameters in obese subjects with type 2 diabetes.

Introduction A combination of drugs is required for treatment of obese subjects with diabetes, due to multiple pathogenic mechanisms implicated in the development of both diabetes and obesity. Objective Assessment of the effect of sitagliptin added to insulin glargine and metformin, in obese subjects with type 2 diabetes. Methods A total of 23 obese subjects on metformin and insulin glargine participated in the study. Titration of insulin glargine during a one-month period preceded the addition of 100 mg of sitagliptin daily. Body mass index, waist circumference, fasting, and prandial glucose were measured monthly, lipids and hemoglobin A1c (HbA1c) every three months, insulin, c-peptide and glucagon at the start and after six months of treatment. Homeostatic models for insulin secretion (HOMA B) and insulin resistance (HOMA IR) were calculated. Results Participants were 58.65 ± 7.62 years of age with a body mass index of 35.06 ± 5.15 kg/m², waist circumference of 115.04 ± 15.5 cm, and the duration of diabetes of 4.11 ± 2.57 years. With the titration of insulin glargine, target fasting glucose levels were not achieved. Waist circumference and body mass index decreased during three months of sitagliptin treatment, thereafter remaining stable. HbA1c decreased significantly after three and six months of therapy. C-peptide increased significantly, while glucagon level fell. HOMA indexes were unchanged. Conclusion Sitagliptin can improve diabetes control and induce modest weight loss in obese subjects poorly controlled on insulin glargine and metformin. Titration of insulin glargine to optimal fasting glucose values is a prerequisite of success of this combination therapy.
Roles of Macrophage Subtypes in Bowel Anastomotic Healing and Anastomotic Leakage

Macrophages play an important role in host defense, in addition to the powerful ability to phagocytose pathogens or foreign matters. They fulfill a variety of roles in immune regulation, wound healing, and tissue homeostasis preservation. Macrophages are characterized by high heterogeneity, which can polarize into at least two major extremes, M1-type macrophages (classical activation) which are normally derived from monocytes and M2-type macrophages (alternative activation) which are mostly those tissue-resident macrophages. Based on the wound healing process in skin, the previous studies have documented how these different subtypes of macrophages participate in tissue repair and remodeling, while the mechanism of macrophages in bowel anastomotic healing has not yet been established. This review summarizes the currently available evidence regarding the different roles of polarized macrophages in the physiological course of anastomotic healing and their pathological roles in anastomotic leakage, the most dangerous complication after gastrointestinal surgery.
Arrays of Point-Absorbing Wave Energy Converters in Short-Crested Irregular Waves

For most wave energy technology concepts, large-scale electricity production and cost-efficiency require that the devices are installed together in parks. The hydrodynamical interactions between the devices will affect the total performance of the park, and the optimization of the park layout and other park design parameters is a topic of active research. Most studies have considered wave energy parks in long-crested, unidirectional waves. However, real ocean waves can be short-crested, with waves propagating simultaneously in several directions, and some studies have indicated that the wave energy park performance might change in short-crested waves. Here, theory for short-crested waves is integrated in an analytical multiple scattering method, and used to evaluate wave energy park performance in irregular, short-crested waves with different number of wave directions and directional spreading parameters. The results show that the energy absorption is comparable to the situation in long-crested waves, but that the power fluctuations are significantly lower.
Liver surface reconstruction for image guided surgery

In image guided surgery, stereo laparoscopes have been introduced to provide a 3D view of the organs during the laparoscopic intervention. This stereo video could possibly be used for other purposes other than simple viewing: such as depth estimation, 3D rendering of the scene and 3D organ modeling. This paper aims at reconstructing 3D liver surface based on stereo vision technique. The estimated surface of the liver can later be used for registration to preoperative 3D model constructed from MRI/CT scans. For this purpose, we resort to a variational disparity estimation technique by minimizing a global energy function over the entire image. More precisely, based on the gray level and gradient constancy assumptions, a data term and a local as well as a nonlocal smoothness terms are defined to build the cost function. The latter is minimized, by using an appropriate optimization technique, to estimate the disparity map. In order to reduce the disparity search range and the influence of noise, the global variational approach is performed on the coarsest level of the multi-resolution pyramidal representation of the stereo images. Then the obtained low-resolution disparity map is up-sampled with a modified joint bilateral filtering method to the original scale. In vivo liver datasets with ground truth is difficult to obtain, so the proposed method is evaluated quantitatively on two cardiac phantom datasets from Hamlyn Center achieving an accuracy of about 2.2 mm for heart1 and 2.1 mm for heart2. Reconstructed points up to 97% for heart1 and 100% for heart2 are obtained. Qualitative validation on in vivo porcine procedure's liver datasets has shown that our proposed method can estimate the untextured surfaces geometry well.
Comparing the Differential Diagnostic Values of 18F-Alfatide II PET/CT between Tuberculosis and Lung Cancer Patients

Purpose To compare the differential diagnostic values of 18F-Alfatide II PET/CT between tuberculosis and lung cancer patients and in patients with sarcoidosis and common inflammation. Methods Nine inflammation patients (4 tuberculosis, 3 sarcoidosis, and 2 common inflammation) and 11 lung cancer patients were included in this study. All patients underwent 18F-FDG and 18F-Alfatide II PET/CT within 2 weeks, followed by biopsy and surgery. The maximized standard uptake value (SUVmax) and the mean standard uptake value (SUVmean) were evaluated. Results The active tuberculosis lesions showed a high accumulation of 18F-FDG, but varying degrees of accumulation of 18F-Alfatide II, including negative results. The SUVmax of 18F-Alfatide II in malignant lesions was significantly higher than that in tuberculosis (4.08 ± 1.51 versus 2.63 ± 1.34, P = 0.0078). Three patients with sarcoidosis showed negative results in 18F-Alfatide II PET/CT. Conclusions The expression of αVβ3 is much lower in tuberculosis as compared to that in lung cancer, and accumulation of 18F-Alfatide II varied even in lesions of the same patient. The negative results of sarcoidosis patients led to the speculation that αVβ3 was not expressed in those lesions.
Exposure to Rabies in Small Indian Mongooses (Herpestes auropunctatus) from Two Regions in Puerto Rico

Abstract The small Indian mongoose (Herpestes auropunctatus) was introduced to several Caribbean Islands to control rat (Rattus spp.) damage to sugarcane plantations. Mongooses failed at suppressing rat populations and are now considered pests throughout most of their introduced range. Importantly, mongooses are rabies reservoirs on several Caribbean Islands. In Puerto Rico, mongooses have been implicated in up to 70% of reported animal rabies cases. There is no rabies vaccination program for wildlife in Puerto Rico, and data on rabies in mongooses are limited. We conducted a serosurvey of mongooses in two different ecologic environments in Puerto Rico: El Yunque National Forest and Cabo Rojo National Wildlife Refuge. We collected 119 serum samples from 112 mongooses, 44 (39.3%) of which were positive for rabies virus–neutralizing antibodies. We also collected oral swabs from 147 mongooses, including 88 from which we also collected serum. No oral swabs were positive for rabies virus RNA. Our data support previous research suggesting rabies virus is circulating within the mongoose population on Puerto Rico.
An interplay between multiple sirtuins promotes completion of DNA replication in cells with short telomeres

The evolutionarily-conserved sirtuin family of histone deacetylases regulates a multitude of DNA-associated processes. A recent genome-wide screen conducted in the yeast Saccharomyces cerevisiae identified Yku70/80, which regulate nonhomologous end-joining (NHEJ) and telomere structure, as being essential for cell proliferation in the presence of the pan-sirtuin inhibitor nicotinamide (NAM). Here, we show that sirtuin-dependent deacetylation of both histone H3 lysine 56 and H4 lysine 16 promotes growth of yku70Δ and yku80Δ cells, and that the NAM sensitivity of these mutants is not caused by defects in DNA double-strand break repair by NHEJ, but rather by their inability to maintain normal telomere length. Indeed, our results indicate that in the absence of sirtuin activity, cells with abnormally short telomeres, e.g., yku70/80Δ or est1/2Δ mutants, present striking defects in S phase progression. Our data further suggest that early firing of replication origins at short telomeres compromises the cellular response to NAM- and genotoxin-induced replicative stress. Finally, we show that reducing H4K16ac in yku70Δ cells limits activation of the DNA damage checkpoint kinase Rad53 in response to replicative stress, which promotes usage of translesion synthesis and S phase progression. Our results reveal a novel interplay between sirtuin-mediated regulation of chromatin structure and telomere-regulating factors in promoting timely completion of S phase upon replicative stress.
NGF Upregulates the Plasminogen Activation Inhibitor-1 in Neurons via the Calcineurin/NFAT Pathway and the Down Syndrome-Related Proteins DYRK1A and RCAN1 Attenuate This Effect

Background Plasminogen activator inhibitor 1 (PAI-1) is a key regulator of the plasminogen activation system. Although several lines of evidence support a significant role of PAI-1 in the brain, the regulation of its expression in neurons is poorly understood. In the present study we tested the hypothesis that NGF induces the upregulation of PAI-1 via the calcineurin/nuclear factor of activated T cells (NFAT) pathway and analysed whether the overexpression of the Down syndrome-related proteins DYRK1A and RCAN1 modulated the effect of NGF on PAI-1 expression. Results NGF upregulated PAI-1 mRNA levels in primary mouse hippocampal neurons cultured for 3 days in vitro and in the rat pheochromocytoma cell line PC12. Reporter gene assays revealed that NGF activated the calcineurin/NFAT pathway in PC12 cells. Induction of PAI-1 by NGF was sensitive to the calcineurin inhibitor FK506 and the specific inhibition of NFAT activation by the cell permeable VIVIT peptide. Activation of calcineurin/NFAT signalling through other stimuli resulted in a much weaker induction of PAI-1 expression, suggesting that other NGF-induced pathways are involved in PAI-1 upregulation. Overexpression of either DYRK1A or RCAN1 negatively regulated NFAT-dependent transcriptional activity and reduced the upregulation of PAI-1 levels by NGF. Conclusion The present results show that the calcineurin/NFAT pathway mediates the upregulation of PAI-1 by NGF. The negative effect of DYRK1A and RCAN1 overexpression on NGF signal transduction in neural cells may contribute to the altered neurodevelopment and brain function in Down syndrome.
The relationship of perceptions of tap water safety with intake of sugar-sweetened beverages and plain water among US adults

Abstract Objective Research is limited on whether mistrust of tap water discourages plain water intake and leads to a greater intake of sugar-sweetened beverages (SSB). The objective of the present study was to examine demographic differences in perceptions of tap water safety and determine if these perceptions are associated with intake of SSB and plain water. Design The study examined perceptions of tap water safety and their cross-sectional association with intake of SSB and plain water. Racial/ethnic differences in the associations of tap water perceptions with SSB and plain water intake were also examined. Setting Nationally weighted data from the 2010 HealthStyles Survey (n 4184). Subjects US adults aged ≥18 years. Results Overall, 13·0 % of participants disagreed that their local tap water was safe to drink and 26·4 % of participants agreed that bottled water was safer than tap water. Both mistrust of tap water safety and favouring bottled water differed by region, age, race/ethnicity, income and education. The associations of tap water mistrust with intake of SSB and plain water were modified by race/ethnicity (P < 0·05). Non-white racial/ethnic groups who disagreed that their local tap water was safe to drink were more likely to report low intake of plain water. The odds of consuming ≥1 SSB/d among Hispanics who mistrusted their local tap water was twice that of Hispanics who did not (OR = 2·0; 95 % CI 1·2, 3·3). Conclusions Public health efforts to promote healthy beverages should recognize the potential impact of tap water perceptions on water and SSB intake among minority populations.
Internet Addiction in Chinese Adolescents in Hong Kong: Assessment, Profiles, and Psychosocial Correlates

Internet addiction behavior was examined in 6,121 Chinese primary and secondary school students in Hong Kong based on the assessment frameworks of Ivan Goldberg and Kimberly Young. Results showed that scales derived from both frameworks (CIA-Goldberg Scale and CIA-Young Scale) were internally consistent and evidence supporting their validity was found. Descriptive statistical analyses revealed that roughly one-fifth of the respondents could be classified as Internet addicted based on either scale. Further analyses showed that Internet-addicted and -nonaddicted respondents differed in their Internet use and related behavior. Logistic regression analyses showed that engagement in certain on-line activities (such as playing on-line games and downloading software) and replacement of pastimes activities (such as watching TV and going out with friends) with Internet activities predicted a higher probability of Internet addiction.
The biological effects of tocotrienol on bone: a review on evidence from rodent models

Osteoporosis causes significant health care and economic burden to society, leading to a relentless search for effective preventive agents. Tocotrienol, a member of the vitamin E family, has demonstrated promising potential as an osteoporosis-preventing agent. This review summarizes evidence on the effects of tocotrienol on bone in animal models. Techniques used to examine the effects of tocotrienol on bone in animals included bone histomorphometry, X-ray microtomography, dual-energy X-ray absorptiometry, bone turnover markers, bone calcium content, and biomechanical strength. Tocotrienol was shown to improve osteoblast number, bone formation, mineral deposition, and bone microarchitecture in osteopenic rats. It also decreased osteoclast number and bone erosion in the rats. Tocotrienol supplementation resulted in an improvement in bone mineral density, although biomechanical strength was not significantly altered in the rats. The beneficial effects of tocotrienol on bone can be attributed to its role as an antioxidant, anti-inflammatory agent, suppressor of the mevalonate pathway, and modulator of genes favorable to bone formation.
Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma

Background The programmed death 1 (PD‐1) inhibitor pembrolizumab has been found to prolong progression‐free and overall survival among patients with advanced melanoma. We conducted a phase 3 double‐blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high‐risk stage III melanoma. Methods Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred. Recurrence‐free survival in the overall intention‐to‐treat population and in the subgroup of patients with cancer that was positive for the PD‐1 ligand (PD‐L1) were the primary end points. Safety was also evaluated. Results At a median follow‐up of 15 months, pembrolizumab was associated with significantly longer recurrence‐free survival than placebo in the overall intention‐to‐treat population (1‐year rate of recurrence‐free survival, 75.4% [95% confidence interval {CI}, 71.3 to 78.9] vs. 61.0% [95% CI, 56.5 to 65.1]; hazard ratio for recurrence or death, 0.57; 98.4% CI, 0.43 to 0.74; P<0.001) and in the subgroup of 853 patients with PD‐L1–positive tumors (1‐year rate of recurrence‐free survival, 77.1% [95% CI, 72.7 to 80.9] in the pembrolizumab group and 62.6% [95% CI, 57.7 to 67.0] in the placebo group; hazard ratio, 0.54; 95% CI, 0.42 to 0.69; P<0.001). Adverse events of grades 3 to 5 that were related to the trial regimen were reported in 14.7% of the patients in the pembrolizumab group and in 3.4% of patients in the placebo group. There was one treatment‐related death due to myositis in the pembrolizumab group. Conclusions As adjuvant therapy for high‐risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrence‐free survival than placebo, with no new toxic effects identified. (Funded by Merck; ClinicalTrials.gov number, NCT02362594; EudraCT number, 2014‐004944‐37.)
Generalisation and specialisation in hoverfly (Syrphidae) grassland pollen transport networks revealed by DNA metabarcoding

Abstract Pollination by insects is a key ecosystem service and important to wider ecosystem function. Most species‐level pollination networks studied have a generalised structure, with plants having several potential pollinators, and pollinators in turn visiting a number of different plant species. This is in apparent contrast to a plant's need for efficient conspecific pollen transfer. The aim of this study was to investigate the structure of pollen transport networks at three levels of biological hierarchy: community, species and individual. We did this using hoverflies in the genus Eristalis, a key group of non‐Hymenopteran pollinators. We constructed pollen transport networks using DNA metabarcoding to identify pollen. We captured hoverflies in conservation grasslands in west Wales, UK, removed external pollen loads, sequenced the pollen DNA on the Illumina MiSeq platform using the standard plant barcode rbcL, and matched sequences using a pre‐existing plant DNA barcode reference library. We found that Eristalis hoverflies transport pollen from 65 plant taxa, more than previously appreciated. Networks were generalised at the site and species level, suggesting some degree of functional redundancy, and were more generalised in late summer compared to early summer. In contrast, pollen transport at the individual level showed some degree of specialisation. Hoverflies defined as “single‐plant visitors” varied from 40% of those captured in early summer to 24% in late summer. Individual hoverflies became more generalised in late summer, possibly in response to an increase in floral resources. Rubus fruticosus agg. and Succisa pratensis were key plant species for hoverflies at our sites Our results contribute to resolving the apparent paradox of how generalised pollinator networks can provide efficient pollination to plant species. Generalised hoverfly pollen transport networks may result from a varied range of short‐term specialised feeding bouts by individual insects. The generalisation and functional redundancy of Eristalis pollen transport networks may increase the stability of the pollination service they deliver.