Miracle-dz/UniFAR-FTUs huggingface dataset:
After 800 Mtp Events, Mortality Due to Hemorrhagic Shock Remains High and Unchanged Despite Several In-Hospital Hemorrhage Control Advancements

ABSTRACT Background: Numerous advancements in hemorrhage control and volume replacement that comprise damage control resuscitation (DCR) have been implemented in the last decade to reduce deaths from bleeding. We sought to determine the impact of DCR interventions on mortality over 12 years in a massive transfusion protocol (MTP) population. We hypothesized that mortality would be decreased in later years, which would have used more DCR interventions. Study Design: This was a retrospective review of all MTP patients treated at a large regional Level I trauma center from 2008 to 2019. Interventions by year of implementation examined included MTP 1:1 ratio (2009), liquid plasma (2010), tranexamic acid (2012), prehospital tourniquets (2013), REBOA/TEG (2017), satellite blood station (2018), and whole blood transfusion (2019). Relative risk and odds of mortality for DCR interventions were examined. Results: There were 824 MTP patients included. The cohort was primarily male (80.6%) injured by penetrating mechanism (68.1%) with median (interquartile range) age 31 years (23–44) and New Injury Severity Score 25 (16–34). Overall mortality was unchanged [(38.3%–56.6%); P = 0.26]. Tourniquets (P = 0.02) and whole blood (WB) (P = 0.03) were associated with lower unadjusted mortality; only tourniquets remained significant after adjustment (OR: 0.39; 95% CI: 0.17–0.89; P = 0.03). Conclusions: Despite lower mortality with use of tourniquets and WB, mortality rates due to hemorrhage have not improved at our high MTP volume institution, suggesting implementation of new in-hospital strategies is insufficient to reduce mortality. Future efforts should be directed toward moving hemorrhage control and effective resuscitation interventions to the injury scene.
LncRNA RUSC1-AS1 promotes osteosarcoma progression through regulating the miR-340-5p and PI3K/AKT pathway

Dysregulation of long noncoding RNA (lncRNA) is frequently involved in the progression and development of osteosarcoma. LncRNA RUSC1-AS1 is reported to be upregulated and acts as an oncogene in hepatocellular carcinoma, cervical cancer and breast cancer. However, its role in osteosarcoma has not been studied yet. In the present study, we investigated the role of RUSC1-AS1 in osteosarcoma both in vitro and in vivo. The results showed that the expression of RUSC1-AS1 was significantly upregulated in osteosarcoma cell line U2OS and HOS compared to that in human osteoblast cell line hFOB1.19. Similar results were found in human samples. Silencing RUSC1-AS1 by siRNA significantly inhibited U2OS and HOS cell proliferation and invasion, measured by CCK-8 and transwell assay. Besides, knockdown of RUSC1-AS1 increased cell apoptosis in osteosarcoma cell lines. In addition, RUSC1-AS1 promoted the epithelial-mesenchymal transition (EMT) process of osteosarcoma cells. In vivo experiments confirmed that RUSC1-AS1 knockdown had an inhibitory effect on osteosarcoma tumor growth. Mechanically, we showed that RUSC1-AS1 directly binds to and inhibits miR-340-5p and activates the PI3K/AKT signaling pathway. In conclusion, our study demonstrated that RUSC1-AS1 promoted osteosarcoma development both in vitro and in vivo through sponging to miR-340-5p and activating the PI3K/AKT signaling pathway. Therefore, RUSC1-AS1 becomes a potential therapeutic target for osteosarcoma.
Chemotactic movement of a polarity site enables yeast cells to find their mates

Significance Many cells use extracellular chemical gradients to orient growth or movement in a specific direction. This is critical for development, wound healing, innate immunity, axon guidance, fertilization, and many other processes. However, how cells convert a chemical gradient into a directional response is poorly understood. We use the budding yeast as a model system for gradient sensing and combine experiments and computational modeling to propose a mechanism for how a cell can decode complex and dynamic spatial chemical gradients. The mechanism involves exploration by a subcellular front and may yield clues to other search processes where cells extend projections to seek out specific targets. How small eukaryotic cells can interpret dynamic, noisy, and spatially complex chemical gradients to orient growth or movement is poorly understood. We address this question using Saccharomyces cerevisiae, where cells orient polarity up pheromone gradients during mating. Initial orientation is often incorrect, but polarity sites then move around the cortex in a search for partners. We find that this movement is biased by local pheromone gradients across the polarity site: that is, movement of the polarity site is chemotactic. A bottom-up computational model recapitulates this biased movement. The model reveals how even though pheromone-bound receptors do not mimic the shape of external pheromone gradients, nonlinear and stochastic effects combine to generate effective gradient tracking. This mechanism for gradient tracking may be applicable to any cell that searches for a target in a complex chemical landscape.
High through-plane resolution CT imaging with self-supervised deep learning

CT images for radiotherapy planning are usually acquired in thick slices to reduce the imaging dose, especially for pediatric patients, and to lessen the need for contouring and treatment planning on more slices. However, low through-plane resolution may degrade the accuracy of dose calculations. In this paper, a self-supervised deep learning workflow is proposed to synthesize high through-plane resolution CT images by learning from their high in-plane resolution features. The proposed workflow was designed to facilitate neural networks to learn the mapping from low-resolution (LR) to high-resolution (HR) images in the axial plane. During the inference step, the HR sagittal and coronal images were generated by feeding two parallel-trained neural networks with the respective LR sagittal and coronal images to the trained neural networks. The CT simulation images of a cohort of 75 patients with head and neck cancer (1 mm slice thickness) and 200 CT images of a cohort of 20 lung cancer patients (3 mm slice thickness) were retrospectively investigated in a cross-validation manner. The HR images generated with the proposed method were qualitatively (visual quality, image intensity profiles and preliminary observer study) and quantitatively (mean absolute error, edge keeping index, structural similarity index measurement, information fidelity criterion and visual information fidelity in pixel domain) inspected, while taking the original CT images of the head and neck and lung cancer patients as the reference. The qualitative results showed the capability of the proposed method for generating high through-plane resolution CT images with data from both groups of cancer patients. All the improvements in the measure metrics were confirmed to be statistically significant with paired two-sample t-test analysis. The innovative point of the work is that the proposed deep learning workflow for CT image generation with high through-plane resolution in radiotherapy is self-supervised, meaning that it does not rely on ground truth CT images to train the network. In addition, the assumption that the in-plane HR information can supervise the through-plane HR generation is confirmed. We hope that this will inspire more research on this topic to further improve the through-plane resolution of medical images.
ESTIRIL-LACTONAS DE Cryptocarya aschersoniana Mez. (Lauraceae Juss.) COM ATIVIDADE CONTRA Meloidogyne spp. E INTERAÇÃO IN SILICO COM PROVÁVEL FUMARASE DEMeloidogyne hapla

In a previous study, substances with nematicidal properties were detected in the bark of Cryptocarya aschersoniana. Continuing such study, the methanol extract from this plant underwent fractionation guided by in vitro assays with the plant-parasitic nematode Meloidogyne exigua. Two active compounds were isolated and identified by spectroscopic methods as (E)-6-styrylpyran-2-one and (R)-goniothalamin. The latter compound was also active againstMeloidogyne incognita. In silico studies carried out with (R)-goniothalamin and the enzyme fumarate hydratase, which was extracted from the genome of Meloidogyne hapla and modeled using computational methods, suggested that this substance acts against nematodes by binding to a cavity close to the active site of the enzyme.
Cotyledons facilitate the adaptation of early‐maturing soybean varieties to high‐latitude long‐day environments

Abstract Soybean (Glycine max), a typical short‐day plant (SDP) domesticated in temperate regions, has expanded to high latitudes where daylengths are long from soybean emergence to bloom, but rapidly decrease from seed filling to maturity. Cotyledons are well known as the major storage organs in seeds, but it is unclear whether developing cotyledons store flowering substances at filling stage in SD for upcoming seedlings, or instead respond to photoperiod for floral induction after emergence of matured seeds in long‐day (LD). Here, we report that cotyledons accelerate flowering of early‐maturing varieties not resulting from stored floral stimuli but by perceiving photoperiod after emergence. We found that light signal is indispensable to activate cotyledons for floral induction, and flowering promoting gene GmFT2a is required for cotyledon‐dependent floral induction via upregulation of floral identity gene GmAP1. Interestingly, cotyledons are competent to support the entire life cycle of a cotyledon‐only plant to produce seeds, underlying a new photoperiod study system in soybean and other dicots. Taken together, these results demonstrate a substantial role for cotyledons in flowering process, whereby we propose a ‘cotyledon‐based self‐reliance’ model highlighting floral induction from emergence as a key ecological adaptation for rapid flowering of SDPs grown in LD environments at high latitudes.
A qualitative study of autism services and supports in Singapore: Perspectives of service providers, autistic adults and caregivers

The lifelong and complex nature of autism necessitates an array of services and supports spanning across different sectors and providers at different life stages of an autistic individual. However, research has shown that autistic individuals and their families often experience barriers accessing the autism-related services and supports that they need. This is the first qualitative study to explore the provision and coordination of autism services and supports in Singapore from the perspectives of service providers, autistic adults and caregivers. Semi-structured interviews with 21 participants revealed three main themes: (1) improving access to autism-specific services, (2) creating flexible supports in an inclusive environment and (3) addressing stigma and changing societal attitudes. Our findings suggest that Singapore may have achieved rapid growth in autism services, but broader social structures may be slower to change. To better support autistic individuals in society, autistic voices need to be amplified and a collective effort is needed to achieve a paradigm shift from impairment to capability. Lay abstract Because autism is a lifelong and complex condition, autistic people may need a range of supports cutting across different sectors (e.g. health, education and social care) at different stages of their lives. Studies in some countries have shown that autistic people and their families face difficulties accessing the services they need, but no research has been done on this topic in Singapore. To start addressing this gap, we interviewed 21 service providers, autistic adults and caregivers/parents of autistic children to find out their perceptions and experiences of autism services and supports in Singapore. Our participants told us that beyond improving access to autism-specific services, they also hoped to see more flexible supports in an inclusive environment and a broader change in societal attitudes. This study highlights that autism service provision should be informed by autistic voices and not only focus on impairment but also recognise the strengths of autistic people alongside their very real needs. The whole of society – including policymakers, professionals, employers, educators, families and autistic people themselves – needs to work together to fight autism stigma and discrimination.
In Situ Electric‐Induced Switchable Transparency and Wettability on Laser‐Ablated Bioinspired Paraffin‐Impregnated Slippery Surfaces

Switchable wetting and optical properties on a surface is synergistically realized by mechanical or temperature stimulus. Unfortunately, in situ controllable wettability together with programmable transparency on 2D/3D surfaces is rarely explored. Herein, Joule‐heat‐responsive paraffin‐impregnated slippery surface (JR‐PISS) is reported by the incorporation of lubricant paraffin, superhydrophobic micropillar‐arrayed elastomeric membrane, and embedded transparent silver nanowire thin‐film heater. Owing to its good flexibility, in situ controllable locomotion for diverse liquids on planar/curved JR‐PISS is unfolded by alternately applying/discharging low electric‐trigger of 6 V. Simultaneously, optical visibility can be reversibly converted between opaque and transparent modes. The switching principle is that in the presence of Joule‐heat, solid paraffin would be melt and swell within 20 s to enable a slippery surface for decreasing light scattering and frictional force derived from contact angle hysteresis (FCAH). Once Joule‐heat is discharged, undulating rough surface would reconfigure by cold‐shrinkage of paraffin within 8 s to render light blockage and high FCAH. Upon its portable merit, in situ thermal management, programmable visibility, as well as steering functionalized droplets by electric‐activated JR‐PISSs are successfully deployed. Compared with previous Nepenthes‐inspired slippery surfaces, the current JR‐PISS is more competent for in situ harnessing optical and wetting properties on‐demand.
The role of nucleus of the solitary tract glucagon‐like peptide‐1 and prolactin‐releasing peptide neurons in stress: anatomy, physiology and cellular interactions

Neuroendocrine, behavioural and autonomic responses to stressful stimuli are orchestrated by complex neural circuits. The caudal nucleus of the solitary tract (cNTS) in the dorsomedial hindbrain is uniquely positioned to integrate signals of both interoceptive and psychogenic stress. Within the cNTS, glucagon‐like peptide‐1 (GLP‐1) and prolactin‐releasing peptide (PrRP) neurons play crucial roles in organising neural responses to a broad range of stressors. In this review we discuss the anatomical and functional overlap between PrRP and GLP‐1 neurons. We outline their co‐activation in response to stressful stimuli and their importance as mediators of behavioural and physiological stress responses. Finally, we review evidence that PrRP neurons are downstream of GLP‐1 neurons and outline unexplored areas of the research field. Based on the current state‐of‐knowledge, PrRP and GLP‐1 neurons may be compelling targets in the treatment of stress‐related disorders.
A Biallelic Frameshift Mutation in Nephronectin Causes Bilateral Renal Agenesis in Humans

Visual Abstract Significance Statement Bilateral renal agenesis (BRA) is a lethal form of congenital anomaly of the kidney and urinary tract, usually resulting in perinatal death or justifying termination of pregnancy. The exact causes of this disease are not clear, although genetic factors are considered important. In this study, we describe a pathological homozygous frameshift variant (NPNT:NM_001184690:exon8:c.777dup/p.Lys260*) that is responsible for a recessive form of BRA within a family. A knock-in mouse model mimicking the mutation we found in the family was established and replicated the phenotype of BRA. These results reveal a new genetic cause of BRA and identify a new target for genetic diagnosis, prenatal diagnosis, and preimplantation diagnosis for families with BRA. Background Bilateral renal agenesis (BRA) is a lethal con genital anomaly caused by the failure of normal development of both kidneys early in embryonic development. Oligohydramnios on fetal ultrasonography reveals BRA. Although the exact causes are not clear, BRA is associated with mutations in many renal development genes. However, molecular diagnostics do not pick up many clinical patients. Nephronectin (NPNT) may be a candidate protein for widening diagnosis. It is essential in kidney development, and knockout of Npnt in mice frequently leads to kidney agenesis or hypoplasia. Methods A consanguineous Han family experienced three cases of induced abortion in the second trimester of pregnancy, due to suspected BRA. Whole-exome sequencing (WES)–based homozygosity mapping detected underlying genetic factors, and a knock-in mouse model confirmed the renal agenesis phenotype. Results WES and evaluation of homozygous regions in II:3 and II:4 revealed a pathologic homozygous frameshift variant in NPNT (NM_001184690:exon8:c.777dup/p.Lys260*), which leads to a premature stop in the next codon. The truncated NPNT protein exhibited decreased expression, as confirmed in vivo by the overexpression of WT and mutated NPNT. A knock-in mouse model homozygous for the detected Npnt mutation replicated the BRA phenotype. Conclusions A biallelic loss-of-function NPNT mutation causing an autosomal recessive form of BRA in humans was confirmed by the corresponding phenotype of knock-in mice. Our results identify a novel genetic cause of BRA, revealing a new target for genetic diagnosis, prenatal diagnosis, and preimplantation diagnosis for families with BRA.
A prospective multicentre diagnostic accuracy study for the Truenat tuberculosis assays

Background Bringing reliable and accurate tuberculosis (TB) diagnosis closer to patients is a key priority for global TB control. Molbio Diagnostics have developed the Truenat point-of-care molecular assays for detection of TB and rifampicin (RIF) resistance. Methods We conducted a prospective multicentre diagnostic accuracy study at 19 primary healthcare centres and seven reference laboratories in Peru, India, Ethiopia and Papua New Guinea to estimate the diagnostic accuracy of the point-of-care Truenat MTB, MTB Plus and MTB-RIF Dx assays for pulmonary TB using culture and phenotypic drug susceptibility testing as the reference standard, compared with Xpert MTB/RIF or Ultra. Results Of 1807 enrolled participants with TB signs/symptoms, 24% were culture-positive for Mycobacterium tuberculosis, of which 15% were RIF-resistant. In microscopy centres, the pooled sensitivity of Truenat MTB and Truenat MTB Plus was 73% (95% CI 67–78%) and 80% (95% CI 75–84%), respectively. Among smear-negative specimens, sensitivities were 36% (95% CI 27–47%) and 47% (95% CI 37–58%), respectively. Sensitivity of Truenat MTB-RIF was 84% (95% CI 62–95%). Truenat assays showed high specificity. Head-to-head comparison in the central reference laboratories suggested that the Truenat assays have similar performance to Xpert MTB/RIF. Conclusion We found the performance of Molbio's Truenat MTB, MTB Plus and MTB-RIF Dx assays to be comparable to that of the Xpert MTB/RIF assay. Performing the Truenat tests in primary healthcare centres with very limited infrastructure was feasible. These data supported the development of a World Health Organization policy recommendation of the Molbio assays. Diagnostic performance of point-of-care Truenat assays in primary healthcare centres is comparable to that of Xpert MTB/RIF placed in reference laboratories. The WHO now recommends Truenat as an initial test for detection of TB and RIF resistance. https://bit.ly/31Wj3S6
How Positive Are Conversion Disorder Diagnoses?

Abstract The Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for conversion disorder have replaced the criterion of evidence of a “psychogenic” etiology with a criterion that patients must be “positively” diagnosed on the basis of their neurological assessment. We retrospectively studied referrals to a specialist functional neurology clinic to see how commonly the new criteria were met since DSM-5's introduction. Positive signs were reported in a quarter of referrals (26.5%), which was associated with diagnosticians' confidence (p = 0.001) and with the clinic confirming the diagnosis (p = 0.01). Our clinic found positive signs in 28.6% of the referrals. In 13 (13.3%) patients, the new criterion was not met. In conclusion, positive signs are diagnostically helpful but are only reported in a minority of assessments. A significant group of those currently believed to have conversion disorder would not meet the revised diagnostic criteria based on this.
Targeted modification of the Per2 clock gene alters circadian function in mPer2luciferase (mPer2Luc) mice

Modification of the Per2 clock gene in mPer2Luc reporter mice significantly alters circadian function. Behavioral period in constant dark is lengthened, and dissociates into two distinct components in constant light. Rhythms exhibit increased bimodality, enhanced phase resetting to light pulses, and altered entrainment to scheduled feeding. Mechanistic mathematical modelling predicts that enhanced protein interactions with the modified mPER2 C-terminus, combined with differential clock regulation among SCN subregions, can account for effects on circadian behavior via increased Per2 transcript and protein stability. PER2::LUC produces greater suppression of CLOCK:BMAL1 E-box activity than PER2. mPer2Luc carries a 72 bp deletion in exon 23 of Per2, and retains a neomycin resistance cassette that affects rhythm amplitude but not period. The results show that mPer2Luc acts as a circadian clock mutation illustrating a need for detailed assessment of potential impacts of c-terminal tags in genetically modified animal models.
Arginine methylation and cytoplasmic mRNA fate: An exciting new partnership

Posttranslational modifications play a crucial role in regulating gene expression. Among these modifications, arginine methylation has recently attracted tremendous attention due to its role in multiple cellular functions. This review discusses the recent advances that have established arginine methylation as a major player in determining cytoplasmic messenger RNA (mRNA) fate. We specifically focus on research that implicates arginine methylation in regulating mRNA translation, decay, and RNA granule dynamics. Based on this research, we highlight a few emerging future avenues that will lead to exciting discoveries in this field.
Mediating effect of genome-wide DNA methylation on suicidal ideation induced by perceived stress

Supplemental Digital Content is available in the text. Stress is an important risk factor for suicidal ideation, but the mechanisms that link stress, suicidal ideation and neurobiology remain unclear. Epigenetic mechanisms are involved in both vulnerability to suicidal behavior and stress. This is a pilot study of 60 patients with schizophrenia spectrum disorders (36 men and 24 women), with an average age of 43.75 ± 12.24 years. We analyzed the effects of (1) perceived stress and (2) the mediation of genome-wide methylation (~450 000 CpG sites) on suicidal ideation severity. The top CpG site mediating the effect of stress on suicidal ideation was the cg10782349 located in the ZNF701 gene on chromosome 19, facilitating the effect through DNA hypermethylation. These preliminary results indicate that DNA methylation in peripheral tissues can clarify the complex relationship between stress and suicidal ideation in schizophrenia.