Miracle-dz/UniFAR-FTUs huggingface dataset:
Archaeology and art in context: Excavations at the Gunu Site Complex, Northwest Kimberley, Western Australia

The Kimberley region of Western Australia is one of the largest and most diverse rock art provenances in the world, with a complex stylistic sequence spanning at least 16 ka, culminating in the modern art-making of the Wunumbal people. The Gunu Site Complex, in the remote Mitchell River region of the northwest Kimberley, is one of many local expressions of the Kimberley rock art sequence. Here we report excavations at two sites in this complex: Gunu Rock, a sand sheet adjacent to rock art panels; and Gunu Cave, a floor deposit within an extensive rockshelter. Excavations at Gunu Rock provide evidence for two phases of occupation, the first from 7–8 to 2.7 ka, and the second from 1064 cal BP. Excavations at Gunu Rock provide evidence for occupation from the end of the second phase to the recent past. Stone for tools in the early phase were procured from a variety of sources, but quartz crystal reduction dominated the second occupation phase. Small quartz crystals were reduced by freehand percussion to provide small flake tools and blanks for manufacturing small points called nguni by the Wunambal people today. Quartz crystals were prominent in historic ritual practices associated with the Wanjina belief system. Complex methods of making bifacially-thinned and pressure flaked quartzite projectile points emerged after 2.7 ka. Ochre pigments were common in both occupation phases, but evidence for occupation contemporaneous with the putative age of the oldest rock art styles was not discovered in the excavations. Our results show that developing a complete understanding of rock art production and local occupation patterns requires paired excavations inside and outside of the rockshelters that dominate the Kimberley.
The Antimicrobial Properties of Chitosan Can Be Tailored by Formulation

Topical administration of drugs into the vagina can provide local therapy of vaginal infections, preventing the possible systemic side effects of the drugs. The natural polysaccharide chitosan is known for its excellent mucoadhesive properties, safety profile, and antibacterial effects, and thus it can be utilized in improving localized vaginal therapy by prolonging the residence time of a drug at the vaginal site while acting as an antimicrobial in synergy. Therefore, we aimed to explore the potential of chitosan, namely chitosan-coated liposomes and chitosan hydrogel, as an excipient with intrinsic antimicrobial properties. Liposomes were prepared by the thin-film hydration method followed by vesicle size reduction by sonication to the desired size, approximately 200 nm, and coated with chitosan (0.01, 0.03, 0.1, and 0.3%, w/v, respectively). The mucoadhesive properties of chitosan-coated liposomes were determined through their binding efficiency to mucin compared to non-coated liposomes. Non-coated liposomal suspensions were incorporated in chitosan hydrogels forming the liposomes-in-hydrogel formulations, which were further assessed for their texture properties in the presence of biological fluid simulants. The antibacterial effect of chitosan-coated liposomes (0.03%, 0.1% and 0.3%, w/v) and chitosan hydrogels (0.1% and 0.3%, w/w) on Staphylococcus epidermidis and Staphylococcus aureus was successfully confirmed.
Ovitraps Provide a Reliable Estimate of Wolbachia Frequency during wMelBr Strain Deployment in a Geographically Isolated Aedes aegypti Population

Deployment of Aedes aegypti mosquitoes carrying the endosymbiont bacterium Wolbachia has been identified as a promising strategy to reduce dengue, chikungunya, and Zika transmission. We investigated whether sampling larvae from ovitraps can provide reliable estimates on Wolbachia frequency during releases, as compared to the expensive adult-based BG-Sentinel. We conducted pilot releases in a semi-field system (SFS) divided into six cages of 21 m2, each with five ovitraps. Five treatments were chosen to represent different points of a hypothetical invasion curve: 10%, 25%, 50%, 75%, and 90% of Wolbachia frequency. Collected eggs were counted and hatched, and the individuals from a net sample of 27% of larvae per treatment were screened for Wolbachia presence by RT-qPCR. Ovitrap positioning had no effect on egg hatching rate. Treatment strongly affected the number of eggs collected and also the hatching rate, especially when Wolbachia was at a 10% frequency. A second observation was done during the release of Wolbachia in Rio under a population replacement approach when bacterium frequency was estimated using 30 BG-Sentinel traps and 45 ovitraps simultaneously. By individually screening 35% (N = 3904) of larvae collected by RT-qPCR, we were able to produce a similar invasion curve to the one observed when all adults were individually screened. If sampling is reduced to 20%, monitoring Wolbachia frequency with 45 ovitraps would be roughly half the cost of screening all adult mosquitoes captured by 30 BG-Sentinels. Our findings support the scale-up of Wolbachia releases, especially in areas with limited resources to afford massive trapping with BG-Sentinel traps.
Studying Human Neurodevelopment and Diseases Using 3D Brain Organoids

In vitro differentiation of pluripotent stem cells provides a systematic platform to study development and disease. Recent advances in brain organoid technology have created new opportunities to investigate the formation and function of the human brain, under physiological and pathological conditions. In vitro differentiation of pluripotent stem cells provides a systematic platform to study development and disease. Recent advances in brain organoid technology have created new opportunities to investigate the formation and function of the human brain, under physiological and pathological conditions. Brain organoids can be generated to model the cellular and structural development of the human brain, and allow the investigation of the intricate interactions between resident neural and glial cell types. Combined with new advances in gene editing, imaging, and genomic analysis, brain organoid technology can be applied to address questions pertinent to human brain development, disease, and evolution. However, the current iterations of brain organoids also have limitations in faithfully recapitulating the in vivo processes. In this perspective, we evaluate the recent progress in brain organoid technology, and discuss the experimental considerations for its utilization. Dual Perspectives Companion Paper: Integrating CRISPR Engineering and hiPSC-Derived 2D Disease Modeling Systems, by Kristina Rehbach, Michael B. Fernando, and Kristen J. Brennand
Automatic bi-objective parameter tuning for inverse planning of high-dose-rate prostate brachytherapy

We present an automatic bi-objective parameter-tuning approach for inverse planning methods for high-dose-rate prostate brachytherapy, which aims to overcome the difficult and time-consuming manual parameter tuning that is currently required to obtain patient-specific high-quality treatment plans. We modelled treatment planning as a bi-objective optimization problem, in which dose-volume-based planning criteria related to target coverage are explicitly separated from organ-sparing criteria. When this model is optimized, a large set of high-quality plans with different trade-offs can be obtained. This set can be visualized as an insightful patient-specific trade-off curve. In our parameter-tuning approach, the parameters of inverse planning methods are automatically tuned, aimed to maximize the two objectives of the bi-objective planning model. By generating trade-off curves for different inverse planning methods, their maximally achievable plan quality can be insightfully compared. Automatic parameter tuning furthermore allows to construct standard parameter sets (class solutions) representing different trade-offs in a principled way, which can be directly used in current clinical practice. In this work, we considered the inverse planning methods IPSA and HIPO. Thirty-nine previously treated prostate cancer patients were included. We compared automatic parameter tuning, random parameter sampling, and the maximally achievable plan quality obtained by directly optimizing the bi-objective planning model with the state-of-the-art optimization software GOMEA. We showed that for each patient, a set of plans with a wide range of trade-offs could be obtained using automatic parameter tuning for both IPSA and HIPO. By tuning HIPO, better trade-offs were obtained than by tuning IPSA. For most patients, automatic tuning of HIPO resulted in plans close to the maximally achievable plan quality obtained by optimizing the bi-objective planning model directly. Automatic parameter tuning was shown to improve plan quality significantly compared to random parameter sampling. Finally, from the automatically-tuned plans, three class solutions were successfully constructed representing different trade-offs.
Role of Endothelial ADAM17 in Early Vascular Changes Associated with Diabetic Retinopathy

ADAM17, a disintegrin and metalloproteinase 17, is a transmembrane metalloproteinase that regulates bioavailability of multiple membrane-bound proteins via ectodomain shedding. ADAM17 activity was shown to contribute to a number of vascular pathologies, but its role in the context of diabetic retinopathy (DR) is not determined. We found that expression and enzymatic activity of ADAM17 are upregulated in human diabetic postmortem retinas and a mouse model of streptozotocin-induced diabetes. To further investigate the contribution of ADAM17 to vascular alterations associated with DR, we used human retinal endothelial cells (HREC) treated with ADAM17 neutralizing antibodies and exposed to glucidic stress and streptozotocin-induced endothelial ADAM17 knockout mice. Evaluation of vascular permeability, vascular inflammation, and oxidative stress was performed. Loss of ADAM17 in endothelial cells markedly reduced oxidative stress evidenced by decreased levels of superoxide, 3-nitrotyrosine, and 4-hydroxynonenal and decreased leukocyte-endothelium adhesive interactions in vivo and in vitro. Reduced leukostasis was associated with decreased vascular permeability and was accompanied by downregulation of intercellular adhesion molecule-1 expression. Reduction in oxidative stress in HREC was associated with downregulation of NAD(P)H oxidase 4 (Nox4) expression. Our data suggest a role for endothelial ADAM17 in DR pathogenesis and identify ADAM17 as a potential new therapeutic target for DR.
TLR5 agonist entolimod reduces the adverse toxicity of TNF while preserving its antitumor effects

Tumor necrosis factor alpha (TNF) is capable of inducing regression of solid tumors. However, TNF released in response to Toll-like receptor 4 (TLR4) activation by bacterial lipopolysaccharide (LPS) is the key mediator of cytokine storm and septic shock that can cause severe tissue damage limiting anticancer applications of this cytokine. In our previous studies, we demonstrated that activation of another Toll-like receptor, TLR5, could protect from tissue damage caused by a variety of stresses including radiation, chemotherapy, Fas-activating antibody and ischemia-reperfusion. In this study, we tested whether entolimod could counteract TNF-induced toxicity in mouse models. We found that entolimod pretreatment effectively protects livers and lungs from LPS- and TNF-induced toxicity and prevents mortality caused by combining either of these agents with the sensitizer, D-galactosamine. While LPS and TNF induced significant activation of apoptotic caspase 3/7, lipid tissue peroxidation and serum ALT accumulation in mice without entolimod treatment, these indicators of toxicity were reduced by entolimod pretreatment to the levels of untreated control mice. Entolimod was effective when injected 0.5–48 hours prior to, but not when injected simultaneously or after LPS or TNF. Using chimeric mice with hematopoiesis differing in its TLR5 status from the rest of tissues, we showed that this protective activity was dependent on TLR5 expression by non-hematopoietic cells. Gene expression analysis identified multiple genes upregulated by entolimod in the liver and cultured hepatocytes as possible mediators of its protective activity. Entolimod did not interfere with the antitumor activity of TNF in mouse hepatocellular and colorectal tumor models. These results support further development of TLR5 agonists to increase tissue resistance to cytotoxic cytokines, reduce the risk of septic shock and enable safe systemic application of TNF as an anticancer therapy.
Impact of diabetes mellitus on coagulation function before and after off-pump coronary artery bypass grafting.

Background This study aims to explore the influence of off-pump coronary artery bypass grafting (OPCABG) on coagulation function and the effects of diabetes on coagulation function during OPCABG. Methods Patients who met the inclusion and exclusion criteria were divided into two groups: diabetes mellitus (DM) and non-diabetes mellitus (NDM) groups. Thromboelastography (TEG) was tested at the following time points: T0, five days after aspirin and clopidogrel therapy, and before OPCABG; T1, returning to care unit after OPCABG; T2, 5 days after aspirin and clopidogrel therapy, and after OPCABG. Results A total of 56 patients were involved. There were no deaths, or no early postoperative thrombotic events and abnormal bleeding after OPCABG. Intra-group comparison: Compared with T0, the R and K value decreased, while the α angle and MA value increased at T1 and T2, in both groups (P<0.05). A significantly statistical difference was found in the multiple comparison at T0, T1 and T2 (P<0.05). The results are as follows: the R value decreased at T1 and increased at T2, but the value remained less than that at T0. After the OPCABG, the K value gradually decreased, while the MA value and α angle gradually increased. Comparison between groups: T1: the R values were lower in the DM group, when compared to the NDM group (t=3.611, P=0.001). The differences in the MA, K and α angle were not statistically significant. T0 and T2: there were no statistically difference in the R, MA, K, α angle and LY30 between the two groups (P>0.05). Conclusions The coagulation function of patients was at a hypercoagulable state at the early stage after OPCABG. The coagulation function was affected by diabetes at the day of OPCABG. However, there was no statistical difference after 5 days of aspirin and clopidogrel therapy following OPCABG.
The Mentalizing Approach to Psychopathology: State of the Art and Future Directions.

Mentalizing is the capacity to understand others and oneself in terms of internal mental states. It is assumed to be underpinned by four dimensions: automatic-controlled, internally-externally focused, self-other, and cognitive-affective. Research suggests that mental disorders are associated with different imbalances in these dimensions. Addressing the quality of mentalizing as part of psychosocial treatments may be helpful for individuals with various mental disorders. We suggest that mentalizing is a helpful transtheoretical and transdiagnostic concept to explain vulnerability to psychopathology and its treatment. This review summarizes the mentalizing approach to psychopathology from a developmental socioecological evolutionary perspective. We then focus on the application of the mentalizing approach to personality disorders, and we review studies that have extended this approach to other types of psychopathology, including depression, anxiety, and eating disorders. We summarize core principles of mentalization-based treatments and preventive interventions and the evidence for their effectiveness. We conclude with recommendations for future research. Expected final online publication date for the Annual Review of Clinical Psychology, Volume 16 is May 7, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Psychotherapists’ perspectives on collaboration and stepped care in outpatient psychotherapy—A qualitative study

Objective Stepped and collaborative care with outpatient psychotherapy as one treatment step is guideline-recommended for mental health care. To date, the experiences and evaluation of psychotherapists regarding collaboration and stepped care have been neglected. In order to improve collaborative mental health care, this qualitative study aimed at identifying psychotherapists’ perspectives and needs within collaboration and stepped care. Methods Semi-structured qualitative interviews with 20 German outpatient psychotherapists were conducted and analyzed applying thematic analysis. The analysis was realized in a recursive process to first identify themes and then relate these themes back to the research questions with regard to collaboration and stepped care. Results Collaboration mainly took place in small networks, with general practitioners and psychiatrists as the most important partners and psychotherapists wishing to intensify collaboration. Main barriers for collaboration were seen in deficient resources and remuneration and in a perceived lack of esteem by other medical specialties. Stepped care was appreciated for intensified collaboration and low-threshold access to care. Doubts were cast on its implementation within current health care conditions, worries concerned a primacy of economic principles instead of patient-orientation. Among further needs, psychotherapists demanded increased knowledge about psychotherapy, especially among general practitioners. Conclusion Psychotherapists expressed ambivalent attitudes towards stepped and collaborative care, substantially influenced by health care conditions and the perceived own standing among care providers. Psychotherapists’ needs within stepped care comprise intensified collaboration, sufficient time, personal and financial resources for collaboration and opportunities for a constructive interprofessional dialogue.
Relationship of Parental Support on Healthy Habits, School Motivations and Academic Performance in Adolescents

The objective of the study was to analyze how parental support relates to the physical activity practice, satisfaction with sports, level of physical activity, academic performance and alcohol consumption. Descriptive cross-sectional study, with 1100 adolescents (12–16 years old), where the factors related to parental support, gender and age acted as independent variables, and satisfaction with sport, level of physical activity (PA), academic performance and alcohol consumption acted as dependent variables. A multivariate statistical analysis was conducted. Adolescents with little parental support show (p < 0.001) more boredom, less fun, worse academic performance and higher alcohol consumption. Gender shows differences (p < 0.001) experiencing girls more boredom, less fun, less PA practice and higher academic performance than boys. Age establishes (p < 0.01) that older adolescents (15–16 years old) experience more boredom, less fun, less PA practice, lower academic performance and higher alcohol consumption than young boys and girls (12–14 years old). Parental support towards PA practice improves healthy habits, benefits academic performance and school satisfaction with physical and sports activity.
Investigation of 4D dose in volumetric modulated arc therapy-based stereotactic body radiation therapy: does fractional dose or number of arcs matter?

Abstract The aim of this study was to assess the impact of fractional dose and the number of arcs on interplay effects when volumetric modulated arc therapy (VMAT) is used to treat lung tumors with large respiratory motions. A three (fractional dose of 4, 7.5 or 12.5 Gy) by two (number of arcs, one or two) VMAT plan was created for 10 lung cancer cases. The median 3D tumor motion was 17.9 mm (range: 8.2–27.2 mm). Ten phase-specific subplans were generated by calculating the dose on each respiratory phase computed tomography (CT) scan using temporally assigned VMAT arcs. We performed temporal assignment of VMAT arcs using respiratory information obtained from infrared markers placed on the abdomens of the patients during CT simulations. Each phase-specific dose distribution was deformed onto exhale phase CT scans using contour-based deformable image registration, and a 4D plan was created by dose accumulation. The gross tumor volume dose of each 4D plan (4D GTV dose) was compared with the internal target volume dose of the original plan (3D ITV dose). The near-minimum 4D GTV dose (D99%) was higher than the near-minimum 3D internal target volume (ITV) dose, whereas the near-maximum 4D GTV dose (D1%) was lower than the near-maximum 3D ITV dose. However, the difference was negligible, and thus the 4D GTV dose corresponded well with the 3D ITV dose, regardless of the fractional dose and number of arcs. Therefore, interplay effects were negligible in VMAT-based stereotactic body radiation therapy for lung tumors with large respiratory motions.
ChExMix: A Method for Identifying and Classifying Protein-DNA Interaction Subtypes

Regulatory proteins can employ multiple direct and indirect modes of interaction with the genome. The ChIP-exo mixture model (ChExMix) provides a principled approach to detecting multiple protein-DNA interaction modes in a single ChIP-exo experiment. ChExMix discovers and characterizes binding event subtypes in ChIP-exo data by leveraging both protein-DNA cross-linking signatures and DNA motifs. In this study, we present a summary of the major features and applications of ChExMix. We demonstrate that ChExMix does not require high-resolution protein-DNA binding assay data to detect binding event subtypes. Specifically, we apply ChExMix to analyze 393 ChIP-seq data profiles in K562 cells. Similar binding event subtypes are discovered across multiple proteins, suggesting the existence of colocalized regulatory protein modules that are recruited to DNA through a particular sequence-specific transcription factor. Our results thus suggest that ChExMix can characterize protein-DNA binding interaction modes using data from multiple types of protein-DNA interaction assays.
Within-day test–retest reliability of an accelerometer-based method for registration of step time symmetry during stair descent after ACL reconstruction and in healthy subjects

ABSTRACT Background: Symmetry during stair descent can potentially be used as an early functional measure after anterior cruciate ligament reconstruction (ACLR). We have developed a novel application of a single accelerometer-based inertial motion unit (IMU) to identify foot strikes and calculate step times in an ordinary stairway. Purpose: To examine within-day test–retest reliability and measurement error of step time and step time symmetry measured with a body-fixed IMU during stair descent in subjects early after ACLR and in healthy subjects. Methods: Subjects after ACLR were tested twice 6 weeks (N = 15) and twice 3 months (N = 26) postoperatively. Eighteen healthy subjects were tested twice on one occasion. Subjects descended a flight of stairs at preferred speed. Trunk accelerometry data were collected with an inertial motion unit (IMU). Mean step times (MSTs) and limb symmetry index (LSI) of MSTs were calculated. Clinical trials registration number: NCT01279759. Results: Intraclass Correlation Coefficient (ICC (1,1)) for within test–retest reliability varied from 0.87 to 0.96 for MSTs and from 0.58 to 0.87 for LSIs. The 95% confidence interval (CI) for a true value varied from ± 0.02 seconds (s) to ± 0.05 s for MSTs and from ± 4.6 percentage points (pp) to ± 6.6 pp for LSIs. Conclusion: Mean step times measured with a body-fixed IMU during stair descent and limb symmetry indexes calculated from these mean step times are precise and reliable during early post-operative rehabilitation after ACLR and in healthy subjects.