Miracle-dz/UniFAR-FTUs huggingface dataset:
Mechanical property characterization of hundreds of single nuclei based on microfluidic constriction channel

As label‐free biomarkers, the mechanical properties of nuclei are widely treated as promising biomechanical markers for cell type classification and cellular status evaluation. However, previously reported mechanical parameters were derived from only around 10 nuclei, lacking statistical significances due to low sample numbers. To address this issue, nuclei were first isolated from SW620 and A549 cells, respectively, using a chemical treatment method. This was followed by aspirating them through two types of microfluidic constriction channels for mechanical property characterization. In this study, hundreds of nuclei were characterized, producing passage times of 0.5 ± 1.2 s for SW620 nuclei in type I constriction channel (n = 153), 0.045 ± 0.047 s for SW620 nuclei in type II constriction channel (n = 215) and 0.50 ± 0.86 s for A549 nuclei in type II constriction channel. In addition, neural network based pattern recognition was used to classify the nuclei isolated from SW620 and A549 cells, producing successful classification rates of 87.2% for diameters of nuclei, 85.5% for passage times of nuclei and 89.3% for both passage times and diameters of nuclei. These results indicate that the characterization of the mechanical properties of nuclei may contribute to the classification of different tumor cells.
Changes in the material properties of the shell during simulated aquatic hibernation in the anoxia-tolerant painted turtle

ABSTRACT Western painted turtles (Chrysemys picta bellii) tolerate anoxic submergence longer than any other tetrapod, surviving more than 170 days at 3°C. This ability is due, in part, to the shell and skeleton simultaneously releasing calcium and magnesium carbonates, and sequestering lactate and H+ to prevent lethal decreases in body fluid pH. We evaluated the effects of anoxic submergence at 3°C on various material properties of painted turtle bone after 60, 130 and 167–170 days, and compared them with those of normoxic turtles held at the same temperature for the same time periods. To assess changes in the mechanical properties, beams (4×25 mm) were milled from the plastron and broken in a three-point flexural test. Bone mineral density, CO2 concentration (a measure of total bone HCO3−/CO32−) and elemental composition were measured using microcomputed tomography, HCO3−/CO32− titration and inductively coupled plasma mass spectrometry (ICP-MS), respectively. Tissue mineral density of the sampled bone beams was not significantly altered by 167–170 days of aquatic overwintering in anoxic or normoxic water, but bone CO2 and Mg were depleted in anoxic compared with normoxic turtles. At this time point, the plastron beams from anoxic turtles yielded at stresses that were significantly smaller and strains that were significantly greater than the plastron beams of normoxic turtles. When data from anoxic and normoxic turtles were pooled, plastron beams had a diminished elastic modulus after 167–170 days compared with those of control turtles sampled on day 1, indicating an effect of prolonged housing of the turtles in 3°C water without access to basking sites. There were no changes in the mechanical properties of the plastron beams at any of the earlier time points in either group. We conclude that anoxic hibernation can weaken the painted turtle's plastron, but likely only after durations that exceed what it might naturally experience. The duration of aquatic overwintering, regardless of oxygenation state, is likely to be an important factor determining the mechanical properties of the turtle shell during spring emergence. Highlighted Article: Anoxic hibernation can weaken the painted turtle's plastron, but the duration of aquatic overwintering, regardless of oxygenation state, may be more important in determining its mechanical properties at spring emergence.
Effect of Chronic Administration of Nickel on Affective and Cognitive Behavior in Male and Female Rats: Possible Implication of Oxidative Stress Pathway

Nickel (Ni) toxicity has been reported to produce biochemical and behavioral dysfunction. The present study was undertaken to examine whether Ni chronic administration can induce alterations of affective and cognitive behavior and oxidative stress in male and female rats. Twenty-four rats, for each gender, divided into control and three test groups (n = 6), were injected intraperitoneally with saline (0.9% NaCl) or NiCl2 (0.25 mg/kg, 0.5 mg/kg and 1 mg/kg) for 8 weeks. After treatment period, animals were tested in the open-field, elevated plus maze tests for anxiety-like behavior, and forced swimming test for depression-like behavior. The Morris Water Maze was used to evaluate the spatial learning and memory. The hippocampus of each animal was taken for biochemical examination. The results showed that Ni administration dose dependently increased anxiety-like behavior in both tests. A significant increase in depression-like symptoms was also exhibited by Ni treated rats. In the Morris Water Maze test, the spatial learning and memory were significantly impaired just in males treated with 1 mg/kg of Ni. With regard to biochemical analysis, activity of catalase (CAT) and superoxide dismutase (SOD) were significantly decreased, while the levels of nitric oxide (NO) and lipid peroxidation (LPO) in the hippocampus were significantly increased in the Ni-treated groups. Consequently, chronic Ni administration induced behavioral and biochemical dysfunctions.
Systematic review of the impact of coparenting interventions on paternal coparenting behaviour

AIMS The aim of this study was to evaluate the efficacy of interventions to support coparenting, how partners relate to and support one another as parents, on paternal outcomes. BACKGROUND Despite societal shifts in gender roles leading to fathers' increasing involvement in parenting and growing recognition of the need for couples-based parenting interventions, fathers have been underrepresented in parenting research. DESIGN Systematic review. DATA SOURCES Medline, Embase, Healthstar, and PsycInfo. REVIEW METHODS We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to identify peer-reviewed articles published up to 2016 that evaluated the effectiveness of coparenting interventions for expectant fathers or fathers of children <18 years. Study quality was assessed using Cochrane risk of bias criteria for Effective Practice and Organisation of Care reviews; Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria were used to summarize quality of the evidence. The primary outcome was coparenting behaviour among men. RESULTS We identified 16 randomized controlled trials that evaluated 14 coparenting interventions. Nine interventions targeted partners in the perinatal period; five targeted parents of children. All but one involved face-to-face contact, but this varied in duration and intensity. Of the 12 trials that examined coparenting outcomes, eight reported an effect on at least one measure of paternal coparenting behaviour. The quality of the evidence was at a low level. CONCLUSION Success was moderate, supporting the need for future research to explore the use of additional approaches to increase efficacy, including technology-based interventions, to improve uptake among men.
Acute effects of electronic and tobacco cigarettes on vascular and respiratory function in healthy volunteers: a cross-over study

Objectives : To assess the acute effects of nicotine-containing electronic cigarettes versus tobacco smoking on vascular and respiratory function and circulating microparticles, particularly platelet microparticles (PMPs, biomarker of haemostasis/thrombosis) and endothelial microparticles (EMPs, biomarker of endothelial function). Methods : Heart rate (HR), blood pressure, reactive hyperaemia index (RHI, microvascular reactivity), augmentation index (arterial stiffness) and respiratory function were assessed in 20 smokers immediately before and after electronic cigarettes use and tobacco smoking. The number of microparticles was determined by flow cytometry using counting beads as a reference. Labelling with Annexin-V was used to detect the total microparticle fraction. EMPs were characterized as CD31+CD42− and PMPs as CD31+CD42+. Results : HR increased after electronic cigarettes use and tobacco smoking (P < 0.001), whereas blood pressure remained unchanged (P > 0.05). RHI (P = 0.006), augmentation index (P = 0.010) but not augmentation index standardized to HR 75 bpm (P > 0.05) increased with electronic cigarettes use but not with tobacco smoking. Following tobacco smoking, there was a significant increase in total microparticles (P < 0.001), EMPs (P < 0.001) and PMPs (P < 0.001). In contrast, electronic cigarettes were only associated with an increase in PMPs (P < 0.001), with no significant changes in the total microparticle fraction or EMPs (all P > 0.05). Peak expiratory flow significantly decreased following electronic cigarettes use (P = 0.019). Conclusion : Our results demonstrate that acute exposure to tobacco smoking as well as electronic cigarettes influences vascular and respiratory function. Where tobacco smoking significantly increased microparticle formation, indicative of possible endothelial injury, electronic cigarettes use induced vasoreactivity and decreased peak expiratory flow. These findings suggest that both electronic cigarettes and tobacco smoking negatively impact vascular function.
Alogliptin + metformin combination for the treatment of type 2 diabetes mellitus

The impact of type 2 diabetes mellitus continues to grow worldwide, with appropriate glycemic management being a cornerstone of treatment to minimize the risk of macrovascular and microvascular complications. While metformin is widely utilized as a first-line agent for patients without a contraindication to therapy, treatment guidelines recommend a variety of options for second-line dual therapy with patient-specific choices depending on assessment of hypoglycemia risk, weight effects, tolerability, cost and other considerations. Incretin-based therapies, inclusive of dipeptidyl peptidase-4 inhibitors, have become a widely utilized group of medications due to their potentially advantageous effects, such as a low risk of hypoglycemia and overall favorable tolerability profile. Accordingly, fixed-dose combination products containing metformin in combination with a dipeptidyl peptidase-4 inhibitor have been developed by several manufacturers. This article summarizes the current evidence for the safety and efficacy of alogliptin and metformin used in combination for the treatment of type 2 diabetes mellitus.
Long-term treatment of severe obesity: are lifestyle interventions still an option?

ABSTRACT Introduction: Following lifestyle intervention programs based on dietary restriction and habitual physical activity, weight loss, however large, is reported to peak within six months. Despite maintenance protocols, only few cases continue to lose weight thereafter. The majority of cases regain weight and adherence to lifestyle changes are fostered by long-term contact with a supportive team. In general, surgical procedures are reported to produce much larger weight loss and to impact more favorably on long-term weight loss maintenance. Areas covered: We performed a PubMed search on lifestyle modification studies, focusing on the role of behavior programs for the long-term management of obesity in comparison with surgical procedures. Behaviorally-achieved weight loss outcomes can be improved by integrating standard behavior therapy with self-regulation cognitive skills, motivational interviewing and/or phone/internet-based recall systems. Expert commentary: Clinically-important long-term weight loss is achievable by behavior therapy in a small proportion of subjects with obesity, however severe, through personalized programs associating lifestyle modification interventions, with procedures aimed at developing commitment and responsibility skills. A new area of research is the integration of cognitive-behavior therapy with bariatric (metabolic) surgery, either pre- or post-operatively, to exploit long-term adherence to healthy diet and habitual physical activity.
Computer-Assisted Compared with Conventional Total Knee Replacement: A Multicenter Parallel-Group Randomized Controlled Trial

Background: We previously reported the short-term radiographic and functional results of a randomized controlled trial (RCT) comparing computer-assisted and conventionally performed total knee replacement. We currently report the 2-year clinical results from this trial. Methods: One hundred and ninety patients were randomly allocated to undergo either computer-assisted or conventional total knee replacement. One hundred and seventy-two patients were available for clinical evaluation at 2 years, and 167 (97%) of those answered all patient-reported outcome measures (PROMs), including the Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Knee Society Score (KSS), visual analog scale (VAS), and EuroQol-5 Dimensions (EQ-5D). Patients and clinical evaluators were blinded to the method of surgery. Surgical outcome was assessed using the Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) criteria to calculate responder rates, divided into high responders, moderate responders, and nonresponders. Results: The computer-assisted group had significantly more improvement than the conventional group in the mean scores for 2 subscales of the KOOS (7.4 for symptoms [p = 0.02] and 16.2 for sport and recreation [p < 0.01]) and in 1 subscale of the WOMAC (8.8 for stiffness [p = 0.03]). The computer-assisted group also had significantly more high responders (82.8%) than the conventional group (68.8%; p = 0.03) at 2 years, with the number needed to treat determined to be 8. Conclusions: In this study, the use of computer navigation provided better pain relief and restored better function than the use of the conventional surgical technique at 2 years after total knee replacement. Level of Evidence: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.
Using deep neural networks for speaker diarisation

Speaker diarisation answers the question “who spoke when? ” in an audio recording. The input may vary, but a system is required to output speaker labelled segments in time. Typical stages are Speech Activity Detection (SAD), speaker segmentation and speaker clustering. Early research focussed on Conversational Telephone Speech (CTS) and Broadcast News (BN) domains before the direction shifted to meetings and, more recently, broadcast media. The British Broadcasting Corporation (BBC) supplied data through the Multi-Genre Broadcast (MGB) Challenge in 2015 which showed the difficulties speaker diarisation systems have on broadcast media data. Diarisation is typically an unsupervised task which does not use auxiliary data or information to enhance a system. However, methods which do involve supplementary data have shown promise. Five semi-supervised methods are investigated which use a combination of inputs: different channel types and transcripts. The methods involve Deep Neural Networks (DNNs) for SAD, DNNs trained for channel detection, transcript alignment, and combinations of these approaches. However, the methods are only applicable when datasets contain the required inputs. Therefore, a method involving a pretrained Speaker Separation Deep Neural Network (ssDNN) is investigated which is applicable to every dataset. This technique performs speaker clustering and speaker segmentation using DNNs successfully for meeting data and with mixed results for broadcast media. The task of diarisation focuses on two aspects: accurate segments and speaker labels. The Diarisation Error Rate (DER) does not evaluate the segmentation quality as it does not measure the number of correctly detected segments. Other metrics exist, such as boundary and purity measures, but these also mask the segmentation quality. An alternative metric is presented based on the F-measure which considers the number of hypothesis segments correctly matched to reference segments. A deeper insight into the segment quality is shown through this metric.
Deriving and exploiting situational information in speech: investigations in a simulated search and rescue scenario

The need for automatic recognition and understanding of speech is emerging in tasks involving the processing of large volumes of natural conversations. In application domains such as Search and Rescue, exploiting automated systems for extracting mission-critical information from speech communications has the potential to make a real difference. Spoken language understanding has commonly been approached by identifying units of meaning (such as sentences, named entities, and dialogue acts) for providing a basis for further discourse analysis. However, this fine-grained identification of fundamental units of meaning is sensitive to high error rates in the automatic transcription of noisy speech. This thesis demonstrates that topic segmentation and identification techniques can be employed for information extraction from spoken conversations by being robust to such errors. Two novel topic-based approaches are presented for extracting situational information within the search and rescue context. The first approach shows that identifying the changes in the context and content of first responders' report over time can provide an estimation of their location. The second approach presents a speech-based topological map estimation technique that is inspired, in part, by automatic mapping algorithms commonly used in robotics. The proposed approaches are evaluated on a goal-oriented conversational speech corpus, which has been designed and collected based on an abstract communication model between a first responder and a task leader during a search process. Results have confirmed that a highly imperfect transcription of noisy speech has limited impact on the information extraction performance compared with that obtained on the transcription of clean speech data. This thesis also shows that speech recognition accuracy can benefit from rescoring its initial transcription hypotheses based on the derived high-level location information. A new two-pass speech decoding architecture is presented. In this architecture, the location estimation from a first decoding pass is used to dynamically adapt a general language model which is used for rescoring the initial recognition hypotheses. This decoding strategy has resulted in a statistically significant gain in the recognition accuracy of the spoken conversations in high background noise. It is concluded that the techniques developed in this thesis can be extended to more application domains that deal with large volumes of natural spoken conversations.
Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach

The G-protein coupled receptors (GPCRs) belong to a large family of diverse receptors that are well recognized as pharmacological targets. However, very few of these receptors have been pursued as oncology drug targets. The Protease-activated receptor 1 (PAR1), which is a G-protein coupled receptor, has been shown to act as an oncogene and is an emerging anti-cancer drug target. In this paper, we provide an overview of PAR1’s biased signaling role in metastatic cancers of the breast, lungs, and ovaries and describe the development of PAR1 inhibitors that are currently in clinical use to treat acute coronary syndromes. PAR1 inhibitor PZ-128 is in a Phase II clinical trial and is being developed to prevent ischemic and thrombotic complication of patients undergoing cardiac catheterization. PZ-128 belongs to a new class of cell-penetrating, membrane-tethered peptides named pepducins that are based on the intracellular loops of receptors targeting the receptor G-protein interface. Application of PZ-128 as an anti-metastatic and anti-angiogenic therapeutic agent in breast, lung, and ovarian cancer is being reviewed.
Nipple viability after nipple‐sparing mastectomy in patients with prior circum‐areolar incisions

Nipple‐areola‐sparing mastectomy (NSM) is becoming more commonplace as it offers a more esthetic breast appearance while still appropriately treating malignancy. However, patients with prior circum‐areolar incisions are often considered at risk for nipple viability. The authors present a case series of all patients undergoing NSM at their institution between 2012 and 2016. Eighteen consecutive female nonsmoking patients underwent 32 NSMs. None of the patients had reconstructive failures including those relating to the nipple‐areola complex (NAC), such as nipple necrosis. NSM is therefore feasible in cases with prior circum‐areolar incisions. These patients can be safely reconstructed with both prosthetic devices and autologous tissue.
Comparative genomic investigation of high-elevation adaptation in ectothermic snakes

Significance Snakes of the genus Thermophis are endemic to the Tibetan plateau and occur at elevations over 3,500 m and present an opportunity to study the genetics mechanisms of adaptation to high-elevation conditions in ectotherms. Here, we provide a de novo genome of the Tibetan hot-spring snake, Thermophis baileyi, and conduct a series of comparisons with other reptiles. We identify genes under positive selection and test properties of allelic variants of proteins that are involved in DNA damage repair and responses to hypoxia. Functional assays reveal convergent genetic mechanisms that underlie high-elevation adaptation in both endotherms and ectotherms. Several previous genomic studies have focused on adaptation to high elevations, but these investigations have been largely limited to endotherms. Snakes of the genus Thermophis are endemic to the Tibetan plateau and therefore present an opportunity to study high-elevation adaptations in ectotherms. Here, we report the de novo assembly of the genome of a Tibetan hot-spring snake (Thermophis baileyi) and then compare its genome to the genomes of the other two species of Thermophis, as well as to the genomes of two related species of snakes that occur at lower elevations. We identify 308 putative genes that appear to be under positive selection in Thermophis. We also identified genes with shared amino acid replacements in the high-elevation hot-spring snakes compared with snakes and lizards that live at low elevations, including the genes for proteins involved in DNA damage repair (FEN1) and response to hypoxia (EPAS1). Functional assays of the FEN1 alleles reveal that the Thermophis allele is more stable under UV radiation than is the ancestral allele found in low-elevation lizards and snakes. Functional assays of EPAS1 alleles suggest that the Thermophis protein has lower transactivation activity than the low-elevation forms. Our analysis identifies some convergent genetic mechanisms in high-elevation adaptation between endotherms (based on studies of mammals) and ectotherms (based on our studies of Thermophis).