Miracle-dz/UniFAR-FTUs huggingface dataset:
Polyglutamine toxicity assays highlight the advantages of mScarlet for imaging in Saccharomyces cerevisiae

Development of fluorescent proteins (FPs) enabled researchers to visualize protein localization and trafficking in living cells and organisms. The extended palette of available FPs allows simultaneous detection of multiple fluorescent fusion proteins. Importantly, FPs are originally derived from different organisms from jelly fish to corals and each FP displays its own biophysical properties. Among these properties, the tendency of FPs to oligomerize inherently affects the behavior of its fusion partner. Here we employed the budding yeast Saccharomyces cerevisiae to determine the impact of the latest generation of red FPs on their binding partner. We used a yeast assay based on the aggregation and toxicity of misfolded polyQ expansion proteins linked to Huntington’s disease. Since polyQ aggregation and toxicity are highly dependent on the sequences flanking the polyQ region, polyQ expansions provide an ideal tool to assess the impact of FPs on their fusion partners. We found that unlike what is observed for green FP variants, yemRFP and yFusionRed-tagged polyQ expansions show reduced toxicity. However, polyQ expansions tagged with the bright synthetically engineered ymScarlet displayed severe polyQ toxicity. Our data indicate that ymScarlet might have significant advantages over the previous generation of red FPs for use in fluorescent fusions in yeast.
Sacrificial Layer Technique for Releasing Metallized Multilayer SU-8 Devices

The low fabrication cost of SU-8-based devices has opened the fields of point-of-care devices (POC), µTAS and Lab-on-Chip technologies, which call for cheap and disposable devices. Often this translates to free-standing, suspended devices and a reusable carrier wafer. This necessitates a sacrificial layer to release the devices from the substrates. Both inorganic (metals and oxides) and organic materials (polymers) have been used as sacrificial materials, but they fall short for fabrication and releasing multilayer SU-8 devices. We propose photoresist AZ 15nXT (MicroChemicals GmbH, Ulm, Germany) to be used as a sacrificial layer. AZ 15nXT is stable during SU-8 processing, making it suitable for fabricating free-standing multilayer devices. We show two methods for cross-linking AZ 15nXT for stable sacrificial layers and three routes for sacrificial release of the multilayer SU-8 devices. We demonstrate the capability of our release processes by fabrication of a three-layer free-standing microfluidic electrospray ionization (ESI) chip and a free-standing multilayer device with electrodes in a microchannel.
Skeletal Muscle Fibrosis in Pancreatic Cancer Patients with Respect to Survival

Abstract Background Cancer cachexia is a catabolic condition characterized by skeletal muscle wasting, consequent to tumor burden, which negatively impacts tolerance to cancer therapies and contributes to increased mortality. Partly because of the limited knowledge of the underlying mechanisms of cancer cachexia derived from human studies, however, the ability to therapeutically intervene remains elusive. The purpose of the current study was therefore to better define the phenotype of skeletal muscle obtained from patients with pancreatic ductal adenocarcinoma (PDAC), which has one of the highest rates of cachexia. Methods Morphological analyses were performed on rectus abdominis muscle biopsies obtained from resectable PDAC patients undergoing tumor resection surgery (N = 20) and from weight-stable non-cancer control subjects undergoing benign abdominal surgery (N = 16). PDAC patients with a body weight loss of greater than 5% during the previous 6 months were considered cachectic (N = 15). Statistical tests were two sided. Results Skeletal muscle from cachectic PDAC patients had increased collagen content compared with non-cancer control subjects (1.43% vs 9.66%, P = .0004, Dunn test). Across all PDAC patients, collagen content positively correlated with body weight loss (P = .0016, r = 0.672), was increased in patients with lymph node metastasis (P = .007, Mann-Whitney U test), and was associated with survival on univariate (HR = 1.08, 95% confidence interval [CI] = 1.02 to 1.04, P = .008) and multivariable analyses (HR = 1.08, 95% CI = 1.00 to 1.17, P = .038). Cachectic PDAC patients also displayed increased lipid deposition (2.63% vs 5.72%, P = .042), infiltration of CD68+ macrophages (63.6 cells/mm2 vs 233.8 cells/mm2, P = .0238), calcium deposition (0.21% vs 2.51%, P = .030), and evidence of deficient cellular quality control mechanisms (Mann-Whitney U test). Transcriptional profiling of all patients supported these findings by identifying gene clusters related to wounding, inflammation, and cellular response to TGF-β upregulated in cachectic PDAC patients compared with non-cancer control subjects. Conclusions To our knowledge, this work is the first to demonstrate increased collagen content in cachectic PDAC patients that is associated with poor survival.
Stimulus Level during Endurance Training: Effects on Lactate Kinetics in Untrained Men

Background/Objective Not only but particularly due to their time efficiency, High-Intensity Interval Training (HIIT) is becoming increasingly popular in fitness-oriented endurance sports. The purpose of this study was to determine the effect of a HIIT running program versus a Moderate Intensity Continuous Exercise (MICE) training running program (16 weeks each) on lactate kinetics in untrained males. Methods 65 healthy but untrained males (30-50 years, BMI: 27.2 ± 3.7kg/m2) were randomly assigned to either an HIIT (n=33) or a waiting-control/MICE group (n=32). HIIT consisted of intervals and intense continuous running bouts at or above the individual anaerobic threshold (IANS, 95-110% of IANS-HR), while MICE focused on continuous running at 70-82.5% IANS-HR. Both programs were adjusted for “total workload”. Study endpoints were time to IANS and time from IANS till “time to exhaustion” (TTE) as assessed by stepwise treadmill test. Results In both exercise groups time to reach IANS (MICE: 320 ± 160 s versus HIIT: 198 ± 118 s) increased significantly (p<.001), with the groups differing significantly (p<.001). Time from IANS until TTE was prolonged significantly among the HIIT group (27 ± 66s, p=.030), while among the MICE group a significant reduction of time from IANS until TTE (59 ± 109s; p=.017) was determined. Between-group difference is significant (p=.003) for this parameter. In both groups TTE increased significantly (HIIT: 27.2 ± 17.7% versus MICE: 29.0 ± 19.4%, both p<.001) at a similar level (p=.279). Conclusion HIIT and MICE protocols, when adjusted for total workload, similarly increased running performance in untrained male subjects; however, the underlying mechanisms differ fundamentally. Due to its effects on aerobic and anaerobic performance improvement, HIIT can be recommended for untrained individuals as a time-efficient alternative or complementary training method to MICE. However, our protocol did not confirm the general superiority of HIIT versus MICE on the key endurance parameter “time to exhaustion” that has been reported by other comparative exercise studies.
Celiac Axis Resection with Distal Pancreatectomy (Modified Appleby Procedure) Allows for R0 Resection of Pancreatic Body and Tail Mass Following Neoadjuvant Therapy: Case Report and Literature Review

Abstract Background: The modified Appleby procedure has been developed for cancer of the pancreatic body or tail with celiac axis invasion, historically classified as unresectable disease. Post-Appleby resection, the source of arterial blood to the liver is the superior mesenteric artery, which supplies the gastroduodenal artery and ultimately feeds the proper hepatic artery. In cases of inadequate collateralization, preoperative coiling of the common hepatic artery (CHA) or intraoperative reconstruction via an aorto-hepatic bypass has been described. Method: We describe a 74-year-old female with a pancreatic mass that was initially determined to be unresectable. She underwent extensive combination neoadjuvant chemotherapy. A favorable response was evidenced by a decrease in serum CA 19–9 levels. After 7 months, she was restaged and offered a distal pancreatectomy (DP) with the possibility of a modified Appleby procedure due to potential tumor involvement of the proximal CHA. Results: Intraoperatively, tumor was identified along the CHA traveling proximally to the celiac axis. Therefore, a modified Appleby procedure with DP and splenectomy was performed without the need for reconstruction of the CHA. Postoperative specimen pathology showed residual pancreatic ductal adenocarcinoma with marked treatment effects. The pathology confirmed an R0 resection. The patient followed our postpancreatic surgery care pathway. She remains well 7 months postoperatively. Conclusion: A pancreatic body or tail mass encasing the celiac vessels should not be an immediate referral for palliative care. Recent evidence shows that successful R0 resection can be achieved following neoadjuvant therapy. In fact, patients who have undergone a successful modified Appleby procedure show survival outcomes similar to patients with less advanced cancer who underwent standard DP. The modified Appleby procedure used in conjunction with neoadjuvant therapy can achieve complete resection in select patients previously thought to be unresectable.
Increased physiological dead space at exercise is a marker of mild pulmonary or cardiovascular disease in dyspneic subjects

ABSTRACT Background: The characteristics of cardiopulmonary exercise testing (CPET)-derived parameters for the differential diagnosis of exertional dyspnea are not well known. Objectives: We hypothesized that increased physiological dead space ventilation (VD/Vt) is a marker for mild pulmonary or cardiovascular disease in patients with exertional dyspnea. Design: We used receiver operating characteristic analysis to determine the performance of individual CPET parameters for identifying subjects with either mild pulmonary or cardiovascular disease, among 77 subjects with mild-to-moderate exertional dyspnea (modified Medical Research Council scale 1–2). Results: In comparison with subjects without disease, subjects with pulmonary disease (n = 31) had higher VE/V′CO2 slope, higher VD/Vt, and lower ventilatory reserve. Subjects with cardiovascular disease (n = 14) had lower heart rate and cardiovascular double product and higher VD/Vt at peak exercise. At a threshold of 28%, the sensitivity and specificity of VD/Vt at peak exercise for identifying pulmonary or cardiovascular disease were 89% (95% CI: 64–98%) and 72% (95% CI: 46–89%), respectively. Conclusions: Increased physiological VD/Vt at exercise is a sensitive and specific marker of mild pulmonary or cardiovascular disease in dyspneic subjects.
A Review of Supernumerary Teeth in the Premolar Region

Supernumerary teeth in the premolar region, unlike other supernumeraries, occur more often in the mandible where they are generally of the supplemental type. Occasionally, they are conical or smaller than normal, particularly in the upper premolar regions. They might occur singly or in multiples, be erupted or impacted, but the majority have been found to be unerupted and asymptomatic. The prevalence of supernumerary teeth in the premolar region has been demonstrated to be between 0.01 and 1 percent depending on the population studied. Interestingly, populations from the East or Africa are known to be the most affected. Various theories have been suggested to explain the etiology of supernumerary teeth in general including both genetic and environmental factors. Furthermore, it has been suggested that supernumerary premolar teeth belong to a third (postpermanent) series, developing from extensions of the dental lamina. Several consequences can result from the presence of supernumerary premolars, especially in the mandible, such as cyst formation, transposition, and other clinical scenarios.
Virological Failure in HIV to Triple Therapy With Dolutegravir-Based Firstline Treatment: Rare but Possible

Abstract We describe a case of virological failure during initial treatment with tenofovir disoproxil fumarate/emtricitabine/dolutegravir twice daily, with concomitant rifampin treatment of staphylococcal infection, selection of R263K + E157Q, and low plasma dolutegravir levels. Using rifampin together with dolutegravir may require closer follow-up, and, if possible, plasma dolutegravir levels should be monitored.
Factors Affecting Breast Cancer Detectability on Digital Breast Tomosynthesis and Two-Dimensional Digital Mammography in Patients with Dense Breasts

Objective To compare digital breast tomosynthesis (DBT) and conventional full-field digital mammography (FFDM) in the detectability of breast cancers in patients with dense breast tissue, and to determine the influencing factors in the detection of breast cancers using the two techniques. Materials and Methods Three blinded radiologists independently graded cancer detectability of 300 breast cancers (288 women with dense breasts) on DBT and conventional FFDM images, retrospectively. Hormone status, histologic grade, T stage, and breast cancer subtype were recorded to identify factors affecting cancer detectability. The Wilcoxon signed-rank test was used to compare cancer detectability by DBT and conventional FFDM. Fisher's exact tests were used to determine differences in cancer characteristics between detectability groups. Kruskal-Wallis tests were used to determine whether the detectability score differed according to cancer characteristics. Results Forty breast cancers (13.3%) were detectable only with DBT; 191 (63.7%) breast cancers were detected with both FFDM and DBT, and 69 (23%) were not detected with either. Cancer detectability scores were significantly higher for DBT than for conventional FFDM (median score, 6; range, 0–6; p < 0.001). The DBT-only cancer group had more invasive lobular-type breast cancers (22.5%) than the other two groups (i.e., cancer detected on both types of image [both-detected group], 5.2%; cancer not detected on either type of image [both-non-detected group], 7.3%), and less detectability of ductal carcinoma in situ (5% vs. 16.8% [both-detected group] vs. 27.5% [both-non-detected group]). Low-grade cancers were more often detected in the DBT-only group than in the both-detected group (22.5% vs. 10%, p = 0.026). Human epidermal growth factor receptor-2 (HER-2)-negative cancers were more often detected in the DBT-only group than in the both-detected group (92.3% vs. 70.5%, p = 0.004). Cancers surrounded by mostly glandular tissue were detected less often in the DBT only group than in the both-non-detected group (10% vs. 31.9%, p = 0.016). DBT cancer detectability scores were significantly associated with cancer type (p = 0.012), histologic grade (p = 0.013), T and N stage (p = 0.001, p = 0.024), proportion of glandular tissue surrounding lesions (p = 0.013), and lesion type (p < 0.001). Conclusion Invasive lobular, low-grade, or HER-2-negative cancer is more detectable with DBT than with conventional FFDM in patients with dense breasts, but cancers surrounded by mostly glandular tissue might be missed with both techniques.
Occipitocervical Dislocation in Low-Energy Trauma

Traumatic occipitocervical dislocation (OCD) is described in the literature as a potentially fatal injury secondary to high-energy trauma. We describe a case of OCD occurring in a patient who sustained a ground-level fall whose only clinical symptom was posterior neck pain without neurologic compromise. Computed tomography (CT) and magnetic resonance imaging (MRI) were used to diagnose severe injury to the structurally important ligamentous complex that stabilizes the base of the skull to the spine, along with unstable fractures of the occipital condyle and C1. Emergent surgical instrumentation and fusion of occiput-C2 was performed. Postoperatively, neurologic integrity was maintained. This case illustrates that traumatic OCD is not exclusively secondary to high-energy mechanisms. It also demonstrates that severe neck pain as the only clinical manifestation in a patient with head or neck low-energy trauma is suggestive of a possible OCD. We highlight the importance of the use of head and neck CT as the first imaging-based diagnostic tool to aid in identifying this injury. Finally, surgical stabilization should be performed as soon as possible to minimize neurologic sequelae.
Wild pistachio (Pistacia atlantica mutica) oil improve metabolic syndrome features in rats with high fructose ingestion

Objective(s): Metabolic syndrome is a multiplex risk factor for diabetes and cardiovascular disease. Since some dietary fats such as mono-unsaturated fatty acids (MUFA) modify metabolic syndrome components the aim of the present study was to evaluate the preventive effects of mixture, kernel and hull oils of wild pistachio (WP) (Pistacia atlantica mutica) as good sources of MUFA on different features of this abnormality in rats under induction. Materials and Methods: In this study rats were randomly assigned to six groups with 12 animals per group. Metabolic syndrome was induced by fructose solution in groups 2, 3, 4, 5, and 6. Group 3 received sunflower oil and groups 4, 5, and 6 received mixture, hull and kernel oils of WP (2 ml/kg/day), respectively, for 10 weeks. Then, lipid profiles, glycemic indices, oxidative stress and inflammatory parameters were measured using standard laboratory tests. Results: Different forms of WP oil induced hypotriglyceridemia, but the hypocholesterolemia effect was seen only in the mixed and kernel oil groups. Kernel oil also significantly reduced LDL and HDL cholesterol (P<0.05). In addition, mixed and kernel oils notably decreased glycemic indices (fasting blood glucose and insulin resistance) compared with the fructose group. Serum insulin levels were significantly increased in the kernel oil group (P<0.05). All WP oils also significantly decreased inflammation (IL-6). Conclusion: The results showed that the consumption of WP kernel oil may have beneficial effects on preventing hyperglycemia, hypertriglyceridemia, hypercholesterolemia, inflammation and pancreatic secretory disorders.
Current Status of Magnetic Resonance Imaging in Patients with Malignant Uterine Neoplasms: A Review

In this study, we summarize the clinical role of magnetic resonance imaging (MRI) in the diagnosis of patients with malignant uterine neoplasms, including leiomyosarcoma, endometrial stromal sarcoma, adenosarcoma, uterine carcinosarcoma, and endometrial cancer, with emphasis on the challenges and disadvantages. MRI plays an essential role in patients with uterine malignancy, for the purpose of tumor detection, primary staging, and treatment planning. MRI has advanced in scope beyond the visualization of the many aspects of anatomical structures, including diffusion-weighted imaging, dynamic contrast enhancement-MRI, and magnetic resonance spectroscopy. Emerging technologies coupled with the use of artificial intelligence in MRI are expected to lead to progressive improvement in case management of malignant uterine neoplasms.
Histo-morphological and seminal evaluation of testicular parameters in diabetic rats under antiretroviral therapy: interactions with Hypoxis hemerocallidea

Objective(s): Broad range of metabolic changes associated with highly active antiretroviral therapy (HAART) has been reported over decades including reproductive perturbations. The current study aimed at investigating the role of Hypoxis hemerocallidea (Hyp) in the seminal and morphometric alterations in the testes of streptozotocin-nicotinamide-induced diabetic rats under HAART. Materials and Methods: Sixty-two adult male Sprague-Dawley rats were divided into A-H groups, containing 6 rats in the control group A and 8 rats in the treatment groups B-H. Diabetes was induced by intraperitoneal injection of nicotinamide (110 mg/kg BW) followed by streptozotocin (45 mg/kg BW). The animals were then subjected to various treatments with HAART, Hyp, and melatonin. Results: weights (body and testicular), histological, histochemical, seminal fluid, and morphometric analyses were carried out. Sperm count and motility were reduced in HAART (P<0.05/0.003) and Hyp200 (P<.003) groups compared with normal and diabetic controls, respectively. Sperm count was higher (P<.003) in HAART+ Mel and HAART+Hyp100 groups. Morphometry showed the reduction in germinal epithelium height and basement membrane thickness (P<.003) in the Hyp100 group compared with diabetic controls. Adjuvant use of Hyp and melatonin with HAART did not significantly raise these indices (P>.05). Histological slides showed gross distortions in HAART, diabetic and HAART +Hyp groups with marked atrophy in tubules, germ cell loss and areas of focal depletion of the cell. PAS staining revealed detached basement membrane in diabetic groups with strong PAS-stain. Conclusion: The use of Hyp or melatonin does not ameliorate the testicular damages in diabetic animals under antiretroviral therapy.
Gadolinium Deposition in the Brain: Current Updates

Gadolinium-based contrast agents (GBCAs) are commonly used for enhancement in MR imaging and have long been considered safe when administered at recommended doses. However, since the report that nephrogenic systemic fibrosis is linked to the use of GBCAs in subjects with severe renal diseases, accumulating evidence has suggested that GBCAs are not cleared entirely from our bodies; some GBCAs are deposited in our tissues, including the brain. GBCA deposition in the brain is mostly linked to the specific chelate structure of the GBCA: linear GBCAs were responsible for brain deposition in almost all reported studies. This review aimed to summarize the current knowledge about GBCA brain deposition and discuss its clinical implications.
Chronic administration of ketamine ameliorates the anxiety- and aggressive-like behavior in adolescent mice induced by neonatal maternal separation

Ketamine has long been used as an anesthetic agent. However, ketamine use is associated with numerous side effects, including flashbacks, amnesia, delirium, and aggressive or violent behavior. Ketamine has also been abused as a cocktail with ecstasy, cocaine, and methamphetamine. Several studies have investigated therapeutic applications of ketamine, demonstrating its antidepressant and anxiolytic effects in both humans and rodents. We recently reported that neonatal maternal separation causes enhanced anxiety- and aggressive-like behaviors in adolescent. In the present study, we evaluated how acute and chronic ketamine administration affected the behavioral consequences of neonatal maternal separation in adolescent mice. Litters were separated from dams for 4 hours per day for 19 days beginning after weaning. Upon reaching adolescence (post-natal day 35–49), mice were acutely (single injection) or chronically (7 daily injections) treated with a sub-anesthetic dose (15 mg/kg) of ketamine. At least 1 h after administration of ketamine, mice were subjected to open-field, elevated-plus maze, and resident-intruder tests. We found that acute ketamine treatment reduced locomotor activity. In contrast, chronic ketamine treatment decreased anxiety, as evidenced by increased time spent on open arms in the elevated-plus maze, and remarkably reduced the number and duration of attacks. In conclusion, the present study suggests that ketamine has potential for the treatment of anxiety and aggressive or violent behaviors.