Miracle-dz/UniFAR-FTUs huggingface dataset:
Engineered pH-dependent recycling antibodies enhance elimination of Staphylococcal enterotoxin B superantigen in mice

ABSTRACT A new modality in antibody engineering has emerged in which the antigen affinity is designed to be pH dependent (PHD). In particular, combining high affinity binding at neutral pH with low affinity binding at acidic pH leads to a novel antibody that can more effectively neutralize the target antigen while avoiding antibody-mediated antigen accumulation. Here, we studied how the in vivo pharmacokinetics of the superantigen, Staphylococcal enterotoxin B (SEB), is affected by an engineered antibody with pH-dependent binding. PHD anti-SEB antibodies were engineered by introducing mutations into a high affinity anti-SEB antibody, 3E2, by rational design and directed evolution. Three antibody mutants engineered in the study have an affinity at pH 6.0 that is up to 68-fold weaker than the control antibody. The pH dependency of each mutant, measured as the pH-dependent affinity ratio (PAR – ratio of affinity at pH 7.4 and pH 6.0), ranged from 6.7–11.5 compared to 1.5 for the control antibody. The antibodies were characterized in mice by measuring their effects on the pharmacodynamics and pharmacokinetics (PK) of SEB after co-administration. All antibodies were effective in neutralizing the toxin and reducing the toxin-induced cytokine production. However, engineered PHD antibodies led to significantly faster elimination of the toxin from the circulation than wild type 3E2. The area under the curve computed from the SEB PK profile correlated well with the PAR value of antibody, indicating the importance of fine tuning the pH dependency of binding. These results suggest that a PHD recycling antibody may be useful to treat intoxication from a bacterial toxin by accelerating its clearance.
Illicit fentanyls in the opioid street market: desired or imposed?

BACKGROUND Illicitly manufactured fentanyl and its analogues are appearing in countries throughout the world, often disguised as heroin or counterfeit prescription pills, with resulting high overdose mortality. Possible explanations for this phenomenon include reduced costs and risks to heroin suppliers, heroin shortages, user preferences for a strong, fast-acting opioid and the emergence of Dark Web cryptomarkets. This paper addresses these potential causes and asks three questions: (1) can users identify fentanyl; (2) do users desire fentanyl; and (3) if users want fentanyl, can they express this demand in a way that influences the supply? ARGUMENT/ANALYSIS Existing evidence, while limited, suggests that some users can identify fentanyl, although not reliably, and some desire it, but because fentanyl is frequently marketed deceptively as other drugs, users lack information and choice to express demand effectively. Even when aware of fentanyl's presence, drug users may lack fentanyl-free alternatives. Cryptomarkets, while difficult to quantify, appear to offer buyers greater information and competition than offline markets. However, access barriers and patterns of fentanyl-related health consequences make cryptomarkets unlikely sources of user influence on the fentanyl supply. Market condition data indicate heroin supply shocks and shortages prior to the introduction of fentanyl in the United States and parts of Europe, but the much lower production cost of fentanyl compared with heroin may be a more significant factor CONCLUSION: Current evidence points to a supply-led addition of fentanyl to the drug market in response to heroin supply shocks and shortages, changing prescription opioid availability and/or reduced costs and risks to suppliers. Current drug users in affected regions of the United States, Canada and Europe appear largely to lack both concrete knowledge of fentanyl's presence in the drugs they buy and access to fentanyl-free alternatives.
Three-Dimensional Embryonic Image Segmentation and Registration Based on Shape Index and Ellipsoid-Fitting Method

Quantitative analysis based on three-dimensional differential interference contrast (DIC) images is currently the mainstream in analyzing gene functions involved in early cell fate specifications. Segmentation and registration are the two most important steps in analysis. Many image segmentation methods have poor performance on embryonic DIC images because of the interference of egg shells, blurs, and nonuniform intensity background. A novel segmentation method is presented based on the shape index (SI) of local intensity variation in DIC images. To compute the SI, the intensity values of a local neighborhood are regarded as z coordinates over x-y planes. After calculating the SI for each pixel by evaluating the shape of intensity surface over the corresponding local neighborhood, SI thresholding is used to detect cytoplasm granules within embryonic boundaries. As a scalar and rotation invariant, the SI is both insensitive to directional changes and different ranges of intensity variations. Embryonic registration methods are usually based on the orientation of vertebrate anteroposterior (AP) axes computed from segmented embryonic boundaries. Due to the blur of marginal slices in DIC images, usually the segmented boundaries are incomplete, which may make the computed AP axes shift away from the correct orientation when using the principal component analysis method. A method calculating AP axes based on ellipsoid-fitting is proposed, which can achieve high accuracy when handling incomplete segmented boundaries. Using Worm Developmental Dynamics Database, we evaluated the performance of the proposed segmentation method and the computation of AP axes. Experimental results show that the two methods outperform existing methods.
Global synthesis of conservation studies reveals the importance of small habitat patches for biodiversity

Significance Expansive development for urbanization, agriculture, and resource extraction has resulted in much of the Earth’s vegetation existing as fragmented, isolated patches. Conservation planning typically deprioritizes small, isolated patches, as they are assumed to be of relatively little ecological value, instead focusing attention on conserving large, highly connected areas. Yet, our global analysis shows that, if we gave up on small patches of vegetation, we would stand to lose many species that are confined to those environments, and biodiversity would decline as a result. We should rethink the way we prioritize conservation to recognize the critical role that small, isolated patches play in conserving the world’s biodiversity. Restoring and reconnecting small isolated vegetation patches should be an immediate conservation priority. Island biogeography theory posits that species richness increases with island size and decreases with isolation. This logic underpins much conservation policy and regulation, with preference given to conserving large, highly connected areas, and relative ambivalence shown toward protecting small, isolated habitat patches. We undertook a global synthesis of the relationship between the conservation value of habitat patches and their size and isolation, based on 31 systematic conservation planning studies across four continents. We found that small, isolated patches are inordinately important for biodiversity conservation. Our results provide a powerful argument for redressing the neglect of small, isolated habitat patches, for urgently prioritizing their restoration, and for avoiding simplistic application of island biogeography theory in conservation decisions.
Action recognition using restricted dense trajectories

This paper presents an action recognition algorithm using restricted dense trajectories (RDT). In feature extraction step, restricted dense trajectories are obtained by tracking the refined points in optical flow field, which remove most of meaningless trajectories while preserve the discriminative power. Then we extract a new set of descriptors to capture the appearance and motion information of trajectories. For encoding step, we improve VLAD by assigning each descriptor to their K nearest words and employing these words as basis vectors to linearly approximate the descriptor under the minimum squared error criterion. Experimental results show the proposed algorithm obtains state-of-the-art results.
Evolution of the Population Structure of Staphylococcus pseudintermedius in France

Staphylococcus pseudintermedius is a colonizer as well as an important pathogen of dogs where it is responsible for skin, ear and post-operative infections. The emergence of methicillin-resistant S. pseudintermedius (MRSP) in the early 2000s, which were additionally resistant to most veterinary-licensed antibiotics, drew specific attention to these pathogens due to the limitations created in veterinary therapeutic options. Multiple studies showed that the sequence type (ST)71 was the most frequently identified clone in Europe. A few years ago, several publications have suggested a decline of the ST71 clone and the emergence of the ST258 lineage in Northern Europe. In this study, we show that ST71 is also decreasing over time in France and that the non-ST71 population is highly heterogeneous. Globally, the non-ST71 clones are more susceptible to antibiotics, which might be good news for veterinarians. Two other lineages, ST258 and ST496, seem to be successful in France. These isolates, as well as representatives of the ST71 clone, underwent whole-genome sequence. This study shows that the ST71 and ST496 clusters are highly homogenous while the ST258 cluster is more diverse. Each ST possesses a specific pattern of resistance and virulence genes. The reasons for the apparent and simultaneous success of the ST258 and ST496 clones remain unclear. But the emergence of the ST496 clone will require monitoring given its multi-resistant genotype and threat to canine health.
Salvianolic acid B, an antioxidant derived from Salvia militarize, protects mice against γ-radiation-induced damage through Nrf2/Bach1

Salvianolic acid B (SB) is an antioxidant derived from Salvia militarize, and is one of the most widely used herbs in traditional Chinese medicine. SB is a potent antioxidant that has been well documented as a scavenger of oxygen free radicals, and has been used for the prevention and treatment of atherosclerosis-associated disorders. To explore its potential therapeutic effects in treating radiation damage, in this study, mice were treated with SB at different doses of 5, 12.5 and 20 mg/kg, subsequent to receiving γ-irradiation. The effects of SB on peripheral blood, bone marrow nucleated cells, spleen and thymus indices, and oxidation resistance were evaluated in both radiated mice and control groups. The results indicated that SB significantly increased the counts of peripheral white blood cells, red blood cells and platelets. The number of nucleated cells in the bone marrow and the level of protein increased as well. In addition, improved spleen and thymus indices in the bone marrow were observed. SB treatment additionally reversed the deterioration of both the thymus and spleen indices, which is associated with increased serum superoxide dismutase activity and decreasing malondialdehyde levels via nuclear factor (erythroid-derived 2)-like 2 protein/BTB and CNC homology 1 mediated antioxidant effect. Furthermore, ROS levels and Bax protein expression were also suppressed by SB. The data suggested that SB is effective in protecting mice from γ-radiation injury, and could potentially be applicable for clinical use. Notably, the present study identified a promising candidate drug for enhancing the hematopoietic and immune systems.
Muscle-specific stress fibers give rise to sarcomeres in cardiomyocytes

The sarcomere is the contractile unit within cardiomyocytes driving heart muscle contraction. We sought to test the mechanisms regulating actin and myosin filament assembly during sarcomere formation. Therefore, we developed an assay using human cardiomyocytes to monitor sarcomere assembly. We report a population of muscle stress fibers, similar to actin arcs in non-muscle cells, which are essential sarcomere precursors. We show sarcomeric actin filaments arise directly from muscle stress fibers. This requires formins (e.g., FHOD3), non-muscle myosin IIA and non-muscle myosin IIB. Furthermore, we show short cardiac myosin II filaments grow to form ~1.5 μm long filaments that then ‘stitch’ together to form the stack of filaments at the core of the sarcomere (i.e., the A-band). A-band assembly is dependent on the proper organization of actin filaments and, as such, is also dependent on FHOD3 and myosin IIB. We use this experimental paradigm to present evidence for a unifying model of sarcomere assembly.
Folate receptor targeting of radiolabeled liposomes reduces intratumoral liposome accumulation in human KB carcinoma xenografts

Background Active, ligand-mediated, targeting of functionalized liposomes to folate receptors (FRs) overexpressed on cancer cells could potentially improve drug delivery and specificity. Studies on folate-targeting liposomes (FTLs) have, however, yielded varying results and generally fail to display a clear benefit of FR targeting. Method Tumor accumulating potential of FTLs and NTLs were investigated in a FR overex-pressing xenograft model by positron emission tomography/computed tomography imaging. Results Tumors displayed significantly lower activity of FTLs than NTLs. Furthermore, FTLs displayed worse circulating properties and increased liver-accumulation than NTLs. Conclusion This study underlines that long-circulating properties of liposomes must be achieved to take advantage of EPR-dependent tumor accumulation which may be lost by functionalization. FR-functionalization negatively affected both tumor accumulation and circulation properties.
Serotype distribution, antibiotic resistance pattern, and multilocus sequence types of invasive Streptococcus pneumoniae isolates in two tertiary pediatric hospitals in Beijing prior to PCV13 availability

ABSTRACT Background: Invasive pneumococcal disease (IPD) is a serious threat to children worldwide. This study reported the serotype distribution, antibiotic resistance pattern, and multilocus sequence types of 111 IPD strains isolated from children less than 14 years old in two tertiary pediatric centers in Beijing during the years 2012–2017. Methods: Serotypes were determined using Quellung reaction. Antibiotic resistance was tested using the E-test or disc diffusion method. Sequence types (STs) were assigned via multilocus sequence typing. Results: The most common serotypes of the IPD isolates were 19F, 19A, 14, 23F, and 6B, and the PCV13 coverage rate was 90.1%. For the meningitis isolates, the resistance rate to penicillin was 95.7%, and the non-susceptibility rate to ceftriaxone was 65.2%. All of the non-meningitis isolates were susceptible to penicillin, and the susceptibility rate to ceftriaxone was 89.8%. All but one of the isolates were highly resistant to erythromycin. The multidrug resistance rate of all isolates was 89.2%. The most common STs were ST320, ST271, ST876, and ST81, which belonged to serotype 19A, 19F, 14, and 23F, respectively. Conclusion: Given the high coverage rate of PCV13 and the worrisome non-susceptibility rate of IPD isolates to antibiotics, PCV13 use would be beneficial for Chinese children.
Rehabilitation following spinal cord injury: how animal models can help our understanding of exercise-induced neuroplasticity

Spinal cord injury is a devastating condition that is followed by long and often unsuccessful recovery after trauma. The state of the art approach to manage paralysis and concomitant impairments is rehabilitation, which is the only strategy that has proven to be effective and beneficial for the patients over the last decades. How rehabilitation influences the remodeling of spinal axonal connections in patients is important to understand, in order to better target these changes and define the optimal timing and onset of training. While clinically the answers to these questions remain difficult to obtain, rodent models of rehabilitation like bicycling, treadmill training, swimming, enriched environments or wheel running that mimic clinical rehabilitation can be helpful to reveal the axonal changes underlying motor recovery. This review will focus on the different animal models of spinal cord injury rehabilitation and the underlying changes in neuronal networks that are improved by exercise and rehabilitation.
Turbo-Like Iterative Multi-User Receiver Design for 5G Non-Orthogonal Multiple Access

Non-orthogonal multiple access (NoMA) as an efficient way of radio resource sharing has been identified as a promising technology in 5G to help improving system capacity, user connectivity, and service latency in 5G communications. This paper provides a brief overview of the progress of NoMA transceiver study in 3GPP, with special focus on the design of turbo-like iterative multi-user (MU) receivers. There are various types of MU receivers depending on the combinations of MU detectors and interference cancellation (IC) schemes. Link-level simulations show that expectation propagation algorithm (EPA) with hybrid parallel interference cancellation (PIC) is a promising MU receiver, which can achieve fast convergence and similar performance as message passing algorithm (MPA) with much lower complexity.
Population-Based Study of Risk of AKI with Levetiracetam.

BACKGROUND AND OBJECTIVES Regulatory agencies warn about the risk of AKI with levetiracetam use on the basis of information from case reports. We conducted this study to determine whether new levetiracetam use versus nonuse is associated with a higher risk of AKI. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS This was a population-based retrospective cohort study of adults with epilepsy in Ontario, Canada. Patients who received a new outpatient prescription for levetiracetam between January 1, 2004 and March 1, 2017 were matched to two nonusers on stage of CKD, recorded seizure in the prior 90 days, and logit of a propensity score for levetiracetam use. The primary outcome was a hospital encounter (emergency department visit or hospitalization) with AKI within 30 days of cohort entry. Secondary outcomes were AKI within 180 days and change in the concentration of serum creatinine. We assessed the primary outcome using health care diagnosis codes. We evaluated the change in the concentration of serum creatinine in a subpopulation with laboratory measurements. RESULTS We matched 3980 levetiracetam users to 7960 nonusers (mean age 55 years, 51% women). Levetiracetam use was not significantly associated with a higher risk of AKI within 30 days (13 [0.33%] events in levetiracetam users and 21 [0.26%] events in nonusers [odds ratio, 1.24; 95% confidence interval, 0.62 to 2.47]). Similarly, there was no significant association with AKI within 180 days (odds ratio, 0.70; 95% confidence interval, 0.43 to 1.13). The change in the concentration of serum creatinine did not significantly differ between levetiracetam users and nonusers. CONCLUSIONS In this population-based study levetiracetam use was not associated with a higher risk of AKI. PODCAST This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2018_12_11_Yau_Podcast. mp3.
Effect of Internet-Based Cognitive Behavioral Humanistic and Interpersonal Training vs Internet-Based General Health Education on Adolescent Depression in Primary Care

Key Points Questions Does an internet-based depression prevention program (competent adulthood transition with cognitive behavioral humanistic and interpersonal training) lower the hazard for depression in at-risk adolescents relative to health education attention control? Findings In this randomized clinical trial of adolescents with subsyndromal depression or history of depression randomized to receive internet-based behavioral humanistic interpersonal training or an internet-based general health education control, those who received the CATCH-IT intervention did not evidence fewer episodes of depression in the full intention-to-treat sample, but adolescents with subsyndromal depression may have experienced fewer depressive episodes. Meaning Competent adulthood transition with cognitive behavioral humanistic and interpersonal training may be better than health education for preventing depression in adolescents with subsyndromal depression.
Using Theory to Inform and Guide Perinatal Bereavement Care

Abstract Providing nursing care to perinatally bereaved women and their families is difficult, emotionally demanding, and complicated. Here we demonstrate how, through understanding the theoretical underpinnings of Guided Participation and perinatal grief intensity, nurses can significantly expand their competence and confidence in their ability to provide highly individualized, supportive, relationship-based perinatal bereavement care. The way that parents respond to a perinatal loss may range from little response to highly intense, long-lasting grief. Grief after such losses may be intensified when the loss experience is highly incongruent with a parent's expectations, and the parent is unable to act to reduce this incongruence. The Hutti Perinatal Grief Intensity theoretical framework and the Perinatal Grief Intensity Scale may be used to help identify parents who are likely to experience highly intense grief and need for professional follow-up after perinatal loss. However, many parents who experience intense grief have little experience in coping with such feelings. Guided Participation is a middle-range theory of teaching and learning. It is used in the context of perinatal bereavement to help bereaved parents navigate the feelings and numerous grief-related issues that occur as a consequence of the loss, with the nurse serving as the expert guide. This combined theoretical approach to care assists nurses to assess grief intensity and to provide highly effective, relationship-driven care.
Gynecologists are afraid of prescribing hormone replacement to endometrial/ovarian cancer survivors despite national guidelines—a survey in Sweden

Abstract Background: Prolonged survival in ovarian and endometrial cancer patients increases the importance of paying attention to quality of life. Hormone replacement therapy (HRT) after gynecologic cancer has been controversial. With this survey, we sought to describe Swedish gynecologists’ and gynecologic oncologists’ attitudes towards prescribing HRT to these cancer survivors and see if prescribing practice is consistent with the available evidence and national guidelines. Material and methods: A web-based survey containing three hypothetical cases with a total of 15 questions was distributed to gynecologists and gynecologic oncologists in Sweden. Respondents were asked about their HRT prescription practices in endometrial/ovarian cancer patients with moderate to severe menopausal symptoms. Results: In total 262 gynecologists and 24 gynecologic oncologists answered the survey. In the low-risk endometrial cancer case a majority of the gynecologists (55%) and gynecologic oncologists (66.7%) would prescribe local estrogen. A total of 30% of the gynecologists would prescribe estrogen replacement therapy (ERT) in the high-risk endometrial cancer case compared to 58.3% of the gynecologic oncologists. The gynecologic oncologists felt more comfortable treating patients with endometrial cancer than did gynecologists, and the gynecologists were more likely to read the national guidelines. In the ovarian cancer case, 63.7% of the gynecologists would prescribe HRT compared to 92% of the gynecologic oncologists. Conclusion: Swedish gynecologic oncologists have a more favorable attitude towards HRT for endometrial/ovarian cancer patients and feel more comfortable treating their patients than do gynecologists. This study illustrates a need for education in these matters in order not to withhold HRT from women due to doctors’ sometimes unjustified anxiety.