Miracle-dz/UniFAR-FTUs huggingface dataset:
Predicted structural differences of four fertility‐related Y‐chromosome proteins in Macaca mulatta, M. fascicularis, and their Indochinese hybrids

Species in the genus Macaca typically live in multimale‐multifemale social groups with male macaques exhibiting some of the largest testis: body weight ratios among primates. Males are believed to experience intense levels of sperm competition. Several spermatogenesis genes are located on the Y‐chromosome and, interestingly, occasional hybridization between two species has led to the introgression of the rhesus macaque (Macaca mulatta) Y‐chromosome deep into the range of the long‐tailed macaque (M. fascicularis). These observations have led to the prediction that the successful introgression of the rhesus Y‐haplotype is due to functional differences in spermatogenesis genes compared to those of the native long‐tailed Y‐haplotype. We examine here four Y‐chromosomal loci—RBMY, XKRY, and two nearly identical copies of CDY—and their corresponding protein sequences. The genes were surveyed in representative animals from north of, south of, and within the rhesus x long‐tailed introgression zone. Our results show a series of non‐synonymous amino acid substitutions present between the two Y‐haplotypes. Protein structure modeling via I‐TASSER revealed different folding patterns between the two species' Y‐proteins, and functional predictions via TreeSAAP further reveal physicochemical differences as a result of non‐synonymous substitutions. These differences inform our understanding of the evolution of primate Y‐proteins involved in spermatogenesis and, in turn, have biomedical implications for human male fertility.
Abnormal Functional Connectivity Density in Patients with Dysthyroid Optic Neuropathy

Objective: Functional connectivity density (FCD) mapping was used to investigate abnormalities and factors related to brain functional connectivity in cortical regions of patients with dysthyroid optic neuropathy (DON) and to analyze the pathogenesis of DON further. Methods: Patients diagnosed with thyroid-associated opthalmology (TAO) in the Eye Hospital were enrolled. All patients underwent comprehensive eye examinations and best-corrected visual acuity, visual field (VF) test. MRI data collection and analysis were completed in the 2nd Affiliated Hospital of Wenzhou Medical University. The patients were divided into 2 groups: the DON group, with an average VF, mean deviation (MD) of both eyes < −5 dB, and the non-DON group (nDON group), with an average VF MD of both eyes ≥ −2 dB. Results: A total of 30 TAO patients (14 men, 16 women) with complete data who met the experimental requirements were enrolled. The average age was 48.79 (40–57) years. There were 16 patients in the DON group and 14 patients in the nDON group. No significant differences in age, gender, education level, and the maximum horizontal diameter of either medial rectus muscle were found between the 2 groups. The difference of brain FCD between the 2 groups showed significant abnormal connectivity in the right orbital gyri of the frontal lobe (Frontal_Inf_Orb_R) and the left precuneus in the DON group compared with the nDON group. As demonstrated by decreased FCD values in the right inferior frontal gyrus/orbital part, the relevant brain regions were the left middle temporal gyrus, left precuneus, left middle frontal gyrus, right postcentral gyrus, and brain gyri (excluding the supramarginal gyrus and angular gyrus) below the left parietal bone. The FCD associated with the left precuneus was increased, and the relevant brain areas were the left middle temporal gyrus, right cuneus, superior occipital gyrus, and right fusiform gyrus. A significant correlation was identified between the MD of the binocular VF and brain FCD. Conclusion: The abnormal FCD in the cortex of DON patients suggests that a central nervous system mechanism may be related to the pathogenesis of the DON.
Depiction of Major Mite Allergens in Severe Allergic Rhinitis with High Mite Perennial Exposure.

Objective Airway diseases, including allergic rhinitis, are prompted by specific IgE antibodies against airborne allergens and notably those derived from mites. The presented study focused on the specific IgE immediate response to Dermatophagoides pteronyssinus (D. pteronyssinus) mite major allergens and the corresponding pertinence of molecular diagnosis in patients bothered with severe persistent rhinitis. Methods Individuals exhibiting confirmed sensitization to D. pteronyssinus along with a clinical diagnosis of coexisting severe allergic rhinitis were included in the study. In vivo investigations encompassed intradermal testing with a battery of standardized allergenic extracts, concurrent with in vitro specific IgE to the crude extract of D. pteronyssinus, and associated individual molecular allergens were assessed. Results Fifty-five out of 59 subjects showed serodominant IgE responses to the major allergens Der p 1, Der p 2 and Der p 23. Both Der p 2 and Der p 23 reached a prevalence above 80%, while group 10 allergen tropomyosin was scarcely depicted (<10%) and exclusively present in younger individuals. Conclusion The proposed component-resolved diagnosis panel accurately recognized 93.22% of D. pteronyssinus allergic patients. The raised seroprevalence of IgE response to Der p 23 also confirmed this constituent as a major D. pteronyssinus allergen in severe allergic rhinitis. A molecular approach appears to be essential to frame a more precise diagnosis and eventually a personalized immunotherapy regarding this allergic condition.
Patient Reported Outcomes in Clinical Trials Leading to Cancer Immunotherapy Drug Approvals from 2011 to 2018: A Systematic Review.

BACKGROUND Patient-reported outcomes (PROs) promote patient-centeredness in clinical trials; however, in the field of the rapidly emerging and clinically impressive immunotherapy, data on PROs are limited. METHODS We systematically identified all immunotherapy approvals from 2011 through 2018 and assessed the analytic tools and reporting quality of associated PRO reports. For randomized clinical trials (RCTs), we developed a novel 24-point scoring scale: the PRO Endpoints Analysis Score (PROEAS) based on 24 criteria derived from the recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data (SISAQOL) Consortium. RESULTS We assessed 44 trial publications supporting 42 immunotherapy approvals. PROs were published for 21 of the 44 (47.7%) trial publications. Twenty-three trials (52.3%) were RCTs and 21 (47.7%) pertained to single-arm trials. The median time between primary clinical outcomes publications and their corresponding secondary PRO publications was 19 months (IQR= 9-29). Of the 21 PRO reports, 4 (19.0%) reported a specific hypothesis, and most (85.7%) used descriptive statistics. Three (3 of 21 [14.3%]) studies performed a control for type I error. As for RCTs, 14 of 23 (60.9%) published PRO data including 13 (56.5%) that published a secondary dedicated manuscript. Half of these 14 trials scored < 13 points on the 24-point PROEAS. The mean score was 12.71 (range= 5-17; SD = 3.71), and none met all the recommendations of the SISAQOL Consortium. CONCLUSION Suboptimal reporting of PROs occurs regularly in cancer immunotherapy trials. Increased efforts are needed to maximize the value of this data in cancer immunotherapy development and approval.
Adverse effects of Δ9-tetrahydrocannabinol on neuronal bioenergetics during postnatal development

Ongoing societal changes in views on the medical and recreational roles of cannabis increased the use of concentrated plant extracts with a Δ9-tetrahydrocannabinol (THC) content of more than 90%. Even though prenatal THC exposure is widely considered adverse for neuronal development, equivalent experimental data for young age cohorts are largely lacking. Here, we administered plant-derived THC (1 or 5 mg/kg) to mice daily during P5–P16 and P5–P35 and monitored its effects on hippocampal neuronal survival and specification by high-resolution imaging and iTRAQ proteomics, respectively. We found that THC indiscriminately affects pyramidal cells and both cannabinoid receptor 1+ (CB1R)+ and CB1R– interneurons by P16. THC particularly disrupted the expression of mitochondrial proteins (complexes I–IV), a change that had persisted even 4 months after the end of drug exposure. This was reflected by a THC-induced loss of membrane integrity occluding mitochondrial respiration and could be partially or completely rescued by pH stabilization, antioxidants, bypassed glycolysis, and targeting either mitochondrial soluble adenylyl cyclase or the mitochondrial voltage-dependent anion channel. Overall, THC exposure during infancy induces significant and long-lasting reorganization of neuronal circuits through mechanisms that, in large part, render cellular bioenergetics insufficient to sustain key developmental processes in otherwise healthy neurons.
Research priorities of the autism community: A systematic review of key stakeholder perspectives

In recent years, a shift in focus has seen researchers seek to identify the priorities and preferences of key stakeholders to shape the direction of future research for those on the autism spectrum. The process of synthesising the views, knowledge and expertise of key stakeholders with either a lived or shared experience of autism is invaluable and can inform future research to ensure that it is meaningful and has the greatest impact. A number of studies have reported on the research priorities of groups within the autism community, but to date, these studies stand alone and priorities have not been considered collectively. This systematic review identified seven studies that reported on key stakeholders’ priorities for autism research. Studies were synthesised according to (a) the target participant group and method of recruitment, (b) the methodology used to elucidate the viewpoint of stakeholders, (c) the country of stakeholders and (d) commonly identified priorities. Common features across studies note the importance of prioritising initiatives that will result in real-world changes in the lives of the autism community and more research across the lifespan. There is an identified need for more diverse stakeholder voices to influence the identification of priorities for future research foci. Continued inclusion of the autistic and autism communities in priority-setting research is imperative for achieving significant outcomes in autism research and to progress the field in an effective and socio-ethical way. Lay abstract It has become very important in autism research to ask the autistic community about what kinds of research they think should be done in order to improve the lives of people with autism. Many studies have reported on research goals from people within the autism community, such as parents of people on the autism spectrum, and practitioners and clinicians who support people on the autism spectrum. So far, the research goals from all of these studies have not been considered together, which is important so that all autism research can be working towards the same goals. We reviewed seven studies that looked at the priorities for autism research from key people within the autism community. Each of the reviewed studies are described according to (a) the types of people involved in the study, (b) the way the research goals from each group of people were identified, (c) the country where they were from and (d) the most common research goals from across all of the studies. Within these seven studies, research that will lead to real-world changes in the daily lives of the autism community and a greater focus on skill training for people with autism across their lives were found to be very important. From this review, we found that it is also very important to include a range of different people from the autism community when deciding what autism research goals should be focused on so that future research can be more helpful for the autism community.
Application of Metabolomics in Diagnosis and Treatment of Chronic Liver Diseases

Abstract Chronic liver disease represents stepwise destruction of the liver parenchyma after chronic liver injury, which is often difficult to be diagnosed accurately. Thus, the development of specific biomarkers of chronic liver disease is important. Metabolomics is a powerful tool for biomarker exploration, which enables the exploration of disease pathogenesis or drug action mechanisms at the global metabolic level. The metabolomics workflow generally includes collection, preparation, and analysis of samples, and data processing and bioinformatics. A metabolomics study can simultaneously detect the dysfunctions in the glucose, lipid, amino-acid, and nucleotide metabolisms. Hence, it facilitates the obtaining of a better understanding of the pathogenesis of chronic liver disease and its diagnosis. Many effective drugs could reverse the change of comprehensive biochemical phenotypes induced by chronic liver disease. They can even potentially restore the normal metabolic signatures of patients. Increasingly more researchers have begun to apply metabolomics technologies to diagnose chronic liver disease and investigate the mechanism of action of effective drugs or the variations in drug responses. We are convinced that deepening the understanding of the metabolic alterations could extend their use as powerful biomarkers, promoting the more effective clinical diagnosis and treatment of chronic liver disease in the future.
TJU-DHD: A Diverse High-Resolution Dataset for Object Detection

Vehicles, pedestrians, and riders are the most important and interesting objects for the perception modules of self-driving vehicles and video surveillance. However, the state-of-the-art performance of detecting such important objects (esp. small objects) is far from satisfying the demand of practical systems. Large-scale, rich-diversity, and high-resolution datasets play an important role in developing better object detection methods to satisfy the demand. Existing public large-scale datasets such as MS COCO collected from websites do not focus on the specific scenarios. Moreover, the popular datasets (e.g., KITTI and Citypersons) collected from the specific scenarios are limited in the number of images and instances, the resolution, and the diversity. To attempt to solve the problem, we build a diverse high-resolution dataset (called TJU-DHD). The dataset contains 115354 high-resolution images (52% images have a resolution of $1624\times 1200$ pixels and 48% images have a resolution of at least 2, $560\times 1.440$ pixels) and 709 330 labeled objects in total with a large variance in scale and appearance. Meanwhile, the dataset has a rich diversity in season variance, illumination variance, and weather variance. In addition, a new diverse pedestrian dataset is further built. With the four different detectors (i.e., the one-stage RetinaNet, anchor-free FCOS, two-stage FPN, and Cascade R-CNN), experiments about object detection and pedestrian detection are conducted. We hope that the newly built dataset can help promote the research on object detection and pedestrian detection in these two scenes. The dataset is available at https://github.com/tjubiit/TJU-DHD.
Marine Flatworms: The World of Polyclads

Marine Flatworms provides a fascinating introduction to the intriguing world of polyclad flatworms, a group of large, free-living marine Platyhelminthes, which are found throughout the world but are most colourful in tropical waters. Although not related to molluscs, they are often mistaken for sea slugs because of their brilliant colour patterns. Written in an accessible style by two leading experts in the field, this book explores flatworms’ unusual structure, feeding habits, their curious reproductive behaviour (including ‘penis fencing’), their mimicry and toxicology. With a foreword by Professor Reinhardt Kristensen of the Copenhagen Zoological Museum, Marine Flatworms is the first comprehensive guide to polyclad families and genera. It contains more than 300 colour photographs from every part of the world.
Birth signalling hormones and the developmental consequences of caesarean delivery

Rates of delivery by caesarean section (CS) are increasing around the globe and, although several epidemiological associations have already been observed between CS and health outcomes in later life, more are sure to be discovered as this practice continues to gain popularity. The components of vaginal delivery that protect offspring from the negative consequences of CS delivery in later life are currently unknown, although much attention to date has focused on differences in microbial colonisation. Here, we present the case that differing hormonal experiences at birth may also contribute to the neurodevelopmental consequences of CS delivery. Levels of each of the ‘birth signalling hormones’ (oxytocin, arginine vasopressin, epinephrine, norepinephrine and the glucocorticoids) are lower following CS compared to vaginal delivery, and there is substantial evidence for each that manipulations in early life results in long‐term neurodevelopmental consequences. We draw from the research traditions of neuroendocrinology and developmental psychobiology to suggest that the perinatal period is a sensitive period, during which hormones achieve organisational effects. Furthermore, there is much to be learned from research on developmental programming by early‐life stress that may inform research on CS, as a result of shared neuroendocrine mechanisms at work. We compare and contrast the effects of early‐life stress with those of CS delivery and propose new avenues of research based on the links between the two bodies of literature. The research conducted to date suggests that the differences in hormone signalling seen in CS neonates may produce long‐term neurodevelopmental consequences.
Fragile X Syndrome

The prevalence rate of mathematical learning disabilities (MLD) among children with fragile X syndrome who do not meet criteria for intellectual and developmental disabilities ( 50% of female children) exceeds the rate reported in the general population. The purpose of this article is two-fold: (1) to review the findings on MLD in persons with fragile X syndrome; and (2) to discuss fragile X syndrome as a possible model for understanding pathways to MLD. ' 2009 Wiley-Liss, Inc. Dev Disabil Res Rev 2009;15:21–27.
A simple recipe for solid substitution in porous rocks

Solid substitution refers to computing elastic moduli of a rock with a solid pore fill from moduli of the same rock with a different pore fill (air, fluid or solid). Solid substitution is important for characterisation of rocks saturated with heavy oil or bitumen, rock matrix dissolution and related problems. The dependency of the elastic moduli of the rock on the shear modulus of the pore fill may be much larger than the variation of the solid shear modulus itself. This effect can be caused by uneven distribution of stress within the pore fiill due to the presence of stiff and soft pores. To take these effects into account, we present a simple recipe for solid substitution based on the concept of dual porosity. The input parameters for the model include the dry elastic moduli at the given pressure and at the high-pressure limit. Comparison of the model predictions with ultrasonic measurements on a wax-saturated sandstone shows a reasonable fit for the bulk modulus but a rather poor fit for the shear modulus. The discrepancies might be attributed to the squirt flow dispersion or viscoelasticity of the wax.
How Vehicle Types and Operator’s Legal Status Affect Safety of Interprovincial Buses in Thailand

In urgent response to an unenvied label as the world’ second worst road safety record, the Thai government has begun to ban the use of vans and double-decker buses for intercity bus services and is considering to change the legal status requirement of entities applying for bus operating licenses. This paper examines whether the empirical evidence justifies such policy directions. We use the Poisson and Negative Binomial regression models to examine whether vehicle types and legal status affect safety risks of intercity bus services, focusing on interprovincial routes outside Bangkok. The results confirm that the use of vans and double-decker buses significantly increases fatality risks of interprovincial bus services. But the results produce no evidence to support the claim that formal legal entities provide safer operation. While banning specific vehicle types for bus services is the right policy, our results caution that simply requiring bus operators to obtain formal legal status may not help improve safety performance. More effective policy options should focus on operational characteristics and vehicle standards.
Cytological Observations and In Vitro Germination of Nipa (Nypa fruticans Wurmb., Arecaceae) Pollen

The staminate rachillae from laterals of nipa (Nypa fruticans Wurmb.) at different stages of inflorescence development were sampled for cytological observations using squash technique, with 2% acetocarmine as the stain. Results showed that the dividing microsporocytes exhibited a tetrad in tetragonal shape enclosed in thick callose walls at the end of meiosis II. The microspore products consisted not only of uninucleate but also of binucleate and trinucleate pollen during anthesis. Meiotic stages were interpreted as highly normal, which suggests high pollen viability. In vitro germination observed every 4-h intervals for 24 h showed that sucrose level at 15% attained significantly highest germination at 53%. The germinated pollen developed a knob protrusion instead of an elongated pollen tube. There was a significant difference in pollen knob length at 15% sucrose measuring 9.6 µm, the longest observed, compared to the control. With significant interaction between sucrose and boron levels, 10% and 15% sucrose levels achieved higher in vitro germination when combined with 0.01% and 0.005% boron, respectively. Indeed, sucrose and boric acid consisting of the liquid medium can initiate nipa pollen germination, confirming earlier results with lower concentrations.
Hydraulic Conductivity Behaviour of Low Plastic Clay Subjected to Zinc Contamination

Zinc is released into environment from both natural and anthropogenic sources. The primary sources are related to mining and metallurgic operations involving zinc. Most important sources of zinc come from discharges of slags, wastes, and coal fly ash. Zinc does not volatilize from soil, but remains adsorbed to soil. This paper deals with the change in behaviour of low plasticity kaolinite clay in the presence of zinc. The increase in permeability is undesirable as it lead to consequent leaching to ground water. It can further bio concentrate in aquatic organisms.
A Report on the Munich Internet Research Retreat 2017

This article summarizes the two-day Munich Internet Research Retreat (MIR) held in May 2017. The goal of the retreat was to provide a forum for both academic and industrial researchers to exchange ideas and get feedback on their current work. It was organized in a spirit that is similar to highly interactive “Dagstuhl” seminars, with a very limited number of full-length talks, while dedicating most of the time to poster sessions and group discussions. Presentations delivered during the seminar are made publicly available [20].