Miracle-dz/UniFAR-FTUs huggingface dataset:
Decompressive Surgery for Traumatic Intracranial Hypertension

Intracranial hypertension is the most frequent cause of death or disability following severe traumatic brain injury (TBI). Marked intracranial hypertension due to brain edema reduces the perfusion pressure in capillary blood vessels, leading to hypoxia and further damage to brain tissue through ischemic injury. Thus, intracranial pressure (ICP) monitoring is a recommended standard procedure for the management of severe TBI [1,2]. In addition, first-tier therapies, including head elevation, optimized sedation, normalization of arterial carbon dioxide pressure, and the use of mannitol, hypertonic saline, neuromuscular blockade, and external ventricular drainage are used to control ICP [1]. However, many patients with severe TBI have intracranial hypertension that is refractory to these first-tier therapies, and decompressive procedures, including subtemporal decompression, temporal lobectomy, and hemispheric or bilateral decompressive craniectomy are often required to control ICP. Decompressive craniectomy is the strongest therapy for decreasing ICP. Although the efficacy of the above procedures for improving patient outcome remains controversial, several reports have suggested that decreasing ICP is efficacious [3-6].
Post-traumatic stress disorder or emergence phenomena? A case of psychomotor agitation after procedural sedation and analgesia

Abstract Background Psychomotor agitation can be problematic in an overcrowded emergency department (ED) during uncontrolled procedural sedation. Although emergence phenomena have been studied, various presentations may exist. Case presentation During procedural sedation, a 58-year-old man was sedated with a dissociative dose of ketamine in conjunction with propofol. His shoulder dislocation was reduced successfully but eventually, an exaggerated agitation occurred resembling a post-traumatic stress disorder (PTSD) flashback of past war scenes He was controlled by physical and chemical restraint with an intramuscular injection of 0.1 mg/kg midazolam. After resolution of sedation in rather stable psychiatric conditions, he left the ED with his relatives insisting for discharge against medical advice. Conclusions A PTSD flashback may occur from ketamine sedation in patients with a past history of military experience and can be a manifestation of psychologic adverse effects of ketamine.
Topological Tumor Graphs: a graph-based spatial model to infer stromal recruitment for immunosuppression in melanoma histology.

Despite the advent of immunotherapy, metastatic melanoma represents an aggressive tumor type with a poor survival outcome. The successful application of immunotherapy requires in-depth understanding of the biological basis and immunosuppressive mechanisms within the tumor microenvironment. In this study, we conducted spatially explicit analysis of the stromal-immune interface across 400 melanoma H&E specimens from TCGA (The Cancer Genome Atlas). A computational pathology pipeline (CRImage) was used to classify cells in the H&E specimen into stromal, immune or cancer cells. The estimated proportions of these cell types were validated by independent measures of tumor purity, pathologists' estimate of lymphocyte density, imputed immune cell subtypes and pathway analyses. Spatial interactions between these cell types were computed using a graph-based algorithm (Topological Tumor Graphs: TTGs). This approach identified two stromal features, namely stromal clustering and stromal barrier, which represented the melanoma stromal microenvironment. Tumors with increased stromal clustering and barrier were associated with reduced intratumoral lymphocyte distribution and poor overall survival independent of existing prognostic factors. To explore the genomic basis of these TTG-derived stromal phenotypes, we used a deep learning approach integrating genomic (copy number) and transcriptomic data, thereby inferring a compressed representation of copy number-driven alterations in gene expression. This integrative analysis revealed that tumors with high stromal clustering and barrier had reduced expression of pathways involved in naïve CD4 signalling, MAPK and PI3K signalling. Taken together, our findings support the immunosuppressive role of stromal cells within metastatic melanoma via physical barrier and T cell exclusion within the vicinity of cancer cells.
Using Digital Technology for Sexual and Reproductive Health: Are Programs Adequately Considering Risk?

Digital technologies provide opportunities for advancing sexual and reproductive health and services but also present potential risks. We propose 4 steps to reducing potential harms: (1) consider potential harms during intervention design, (2) mitigate or minimize potential harms during the design phase, (3) measure adverse outcomes during implementation, and (4) plan how to support those reporting adverse outcomes. Digital technologies provide opportunities for advancing sexual and reproductive health and services but also present potential risks. We propose 4 steps to reducing potential harms: (1) consider potential harms during intervention design, (2) mitigate or minimize potential harms during the design phase, (3) measure adverse outcomes during implementation, and (4) plan how to support those reporting adverse outcomes.
Mediator-Free SECM for Probing the Diffusion Layer pH with Functionalized Gold Ultramicroelectrodes

Probing pH gradients during electrochemical reactions is important to better understand reaction mechanisms and to separate the influence of pH and pH gradients from intrinsic electrolyte effects. Here, we develop a pH sensor to measure pH changes in the diffusion layer during hydrogen evolution. The probe was synthesized by functionalizing a gold ultramicroelectrode with a self-assembled monolayer of 4-nitrothiophenol (4-NTP) and further converting it to form a hydroxylaminothiophenol (4-HATP)/4-nitrosothiophenol (4-NSTP) redox couple. The pH sensing is realized by recording the tip cyclic voltammetry and monitoring the Nernstian shift of the midpeak potential. We employ a capacitive approach technique in our home-built Scanning Electrochemical Microscope (SECM) setup in which an AC potential is applied to the sample and the capacitive current generated at the tip is recorded as a function of distance. This method allows for an approach of the tip to the electrode that is electrolyte-free and consequently also mediator-free. Hydrogen evolution on gold in a neutral electrolyte was studied as a model system. The pH was measured with the probe at a constant distance from the electrode (ca. 75 μm), while the electrode potential was varied in time. In the nonbuffered electrolyte used (0.1 M Li2SO4), even at relatively low current densities, a pH difference of three units is measured between the location of the probe and the bulk electrolyte. The time scale of the diffusion layer transient is captured, due to the high time resolution that can be achieved with this probe. The sensor has high sensitivity, measuring differences of more than 8 pH units with a resolution better than 0.1 pH unit.
Hopkins criteria for residual disease assessment after definitive radiotherapy in nasopharyngeal carcinoma

Assessment of viable tumor residue after definitive radiotherapy is essential in patients with nasopharyngeal carcinoma (NPC). This study aimed to investigate the use of Hopkins criteria on positron emission tomography/computed tomography (PET/CT) for posttreatment response evaluation and whether plasma Epstein‐Barr virus (EBV) DNA could bring additional value.
Alpinumisoflavone suppresses human Glioblastoma cell growth and induces cell cycle arrest through activating peroxisome proliferator‐activated receptor‐γ

As a common subtype of malignant gliomas, glioblastoma multiforme (GBM) is associated with poor prognosis. This study is aimed to examine the anticancer activities of alpinumisoflavone (AIF) and its underlying mechanisms. Our results demonstrated that AIF inhibited the proliferation of GBM cells (U373 and T98G) in a time and dose‐dependent manner. In addition, flow cytometry analysis not only confirmed AIF arrested cell cycle at the G0/G1 phase but also the induced apoptosis of U373 and T98G cells. Western blotting also confirmed that AIF altered the expression levels of cell cycle‐related proteins. Further mechanism studies revealed that AIF inhibited cell proliferation, induced G0/G1 phase arrest and induced apoptosis of U373 and T98G cells through activating PPARγ, as evidenced by the fact that GW9662 (PPARγ inhibitor) could effectively reverse the effects of AIF on U373 and T98G cells. Furthermore, the in vivo study also revealed that AIF suppressed tumor growth and caused cell cycle arrest. Collectively, these results highlighted the potential use of AIF in the treatment of GBM.
Efficacy of periacetabular osteotomy followed by progressive resistance training compared to progressive resistance training as non-surgical treatment in patients with hip dysplasia (PreserveHip) – a protocol for a randomised controlled trial

Introduction Periacetabular osteotomy (PAO) is an established treatment for adolescent and adult patients with hip dysplasia. However, the efficacy of PAO has not been tested against another surgical intervention or conservative treatment in a randomised controlled trial before. We suggest that progressive resistance training (PRT) could be an alternative to PAO. The primary aim of this trial is therefore to examine the efficacy of PAO followed by 4 months of usual care followed by 8 months of PRT compared to 12 months of solely PRT in patients with hip dysplasia eligible for PAO in terms of patient-reported pain measured by The Copenhagen Hip and Groin Outcome Score (HAGOS). Methods and analysis This trial is a single-blinded multicentre randomised controlled clinical trial, where patients with hip dysplasia, who are eligible for PAO, will be randomised to either PAO followed by usual care and PRT or PRT only. Primary outcome is patient-reported pain, measured on the subscale pain on the HAGOS questionnaire 12 months after initiation of PAO or PRT. The key secondary outcomes are the other subscales of the HAGOS, adverse and serious adverse events, usage of painkillers (yes/no) and type of analgesics. Based on the sample size calculation, the trial needs to include 96 patients. Ethics and dissemination The trial is approved by the Central Denmark Region Committee on Biomedical Research Ethics (Journal No 1-10-72-234-18) and by the Danish Data Protection Agency (Journal No 1-16-02-120-19). The trial is also approved by The Regional Committee for Medical and Health Research Ethics, Region South-East Norway (Ref. 2018/1603). All results from this trial will be published in international peer-reviewed scientific journals regardless of whether the results are positive, negative or inconclusive. Trial registration number NCT03941171
Cultivation and aerosolization of Stachybotrys chartarum for modeling pulmonary inhalation exposure

Abstract Objective: Stachybotrys chartarum is a hydrophilic fungal species commonly found as a contaminant in water-damaged building materials. Although several studies have suggested that S. chartarum exposure elicits a variety of adverse health effects, the ability to characterize the pulmonary immune responses to exposure is limited by delivery methods that do not replicate environmental exposure. This study aimed to develop a method of S. chartarum aerosolization to better model inhalation exposures. Materials and methods: An acoustical generator system (AGS) was previously developed and utilized to aerosolize and deliver fungal spores to mice housed in a multi-animal nose-only exposure chamber. In this study, methods for cultivating, heat-inactivating, and aerosolizing two macrocyclic trichothecene-producing strains of S. chartartum using the AGS are described. Results and discussion: In addition to conidia, acoustical generation of one strain of S. chartarum resulted in the aerosolization of fungal fragments (<2 µm aerodynamic diameter) derived from conidia, phialides, and hyphae that initially comprised 50% of the total fungal particle count but was reduced to less than 10% over the duration of aerosolization. Acoustical generation of heat-inactivated S. chartarum did not result in a similar level of fragmentation. Delivery of dry, unextracted S. chartarum using these aerosolization methods resulted in pulmonary inflammation and immune cell infiltration in mice inhaling viable, but not heat-inactivated S. chartarum. Conclusions: These methods of S. chartarum growth and aerosolization allow for the delivery of fungal bioaerosols to rodents that may better simulate natural exposure within water-damaged indoor environments.
[Role of protein kinase D1 in regulating the growth, apoptosis and drug sensitivity of oral squamous carcinoma cells].

OBJECTIVE This study aimed to investigate the role of protein kinase D (PKD)1 in regulating the growth, apop-tosis, and drug sensitivity of the squamous carcinoma cell line SCC-25. METHODS The SCC-25 cell line was transfected with either the control-shRNA or PKD1-shRNA plasmids. The stable transfected cells were selected, and the efficiency of PKD1 knockdown was detected by Western blot. The growth and apoptosis of SCC-25 were analyzed with a cell counting kit-8 (CCK8) and flow cytometry. The 50% inhibitory concentrations (IC50) of paclitaxel in the control and PKD1 knockdown cell lines were detected by CCK-8. The expression levels of Bax, Bcl-2, and P-gp were detected by Western blot. RESULTS PKD1 was constitutively expressed and phosphorylated in various cancer cell lines. Inhibiting the expression of PKD1 in SCC-25 cells by RNA interference could inhibit the growth and promote the apoptosis of SCC-25 cells via downregulating Bcl-2 expression. Additionally, inhibiting PKD1 expression could downregulate the expression of P-gp, thereby decreasing both the IC50 and resistance index of paclitaxel. CONCLUSIONS PKD1 plays an important role in regulating the biobehavior of SCC-25. It is a potential therapeutic target for oral squamous carcinoma.
Factors influencing implementation of aerobic exercise after stroke: a systematic review

Abstract Objectives This systematic review aimed to explore the perspectives of healthcare, exercise, and fitness professionals working with people post-stroke regarding the factors affecting the implementation of aerobic exercise after stroke. Data Sources OVID SP MEDLINE, OVID SP EMBASE, and CINAHL were searched from inception to December 2018 using a combination of search terms with synonyms of stroke, aerobic exercise and barriers/facilitators. Review methods Studies focusing on the factors affecting implementation of aerobic exercise after stroke from staff perspectives were included with no restriction on the types of study design. For inclusivity, a broad definition of aerobic exercise was used. Review authors independently extracted data from included studies using domains from the Consolidated Framework for Implementation Research, then synthesised using a framework synthesis approach. Retrospective automated screening was conducted using Rayyan software. Results Twenty studies were included. Four reported on implementation of aerobic exercise, sixteen on general exercise interventions, all post-stroke. Factors identified as influencing implementation of aerobic exercise after stroke included professionals’ self-efficacy and knowledge about stroke, patients’ needs, communication and collaboration within and between organisations and resources such as equipment, staff and training. Conclusions Key factors influencing the implementation of aerobic exercise after stroke included characteristics of the staff and intervention and system-level issues, some of which are modifiable. Further research should evaluate strategies which specifically target these modifiable factors to facilitate implementation in practice. IMPLICATIONS FOR REHABILITATION Aerobic exercise after stroke is an effective intervention but there are challenges to implementation from a staff and system perspective. Any changes to the identified factors should be tailored to suit the staff group and setting. Provision of training and knowledge-sharing could improve staff’s confidence in the prescription and delivery of aerobic exercise after stroke though other implementation strategies should also be considered.
Development and evaluation of an intervention based on the provision of patient feedback to improve patient safety in Spanish primary healthcare centres: study protocol

Introduction Despite the enormous potential for adverse events in primary healthcare (PHC), the knowledge about how to improve patient safety in this context is still sparse. We describe the methods for the development and evaluation of an intervention targeted at PHC professionals to improve patient safety in Spanish PHC centres. Methods and analysis The intervention will consist in using the patient reported experiences and outcomes of safety in primary care (PREOS-PC) survey to gather patient-reported experiences and outcomes concerning the safety of the healthcare patients receive in their PHC centres, and feed that information back to the PHC professionals to help them identify opportunities for safer healthcare provision. The study will involve three stages. Stage 1 (developing the intervention) will involve: (i) qualitative study with 40 PHC providers to optimise the acceptability and perceived utility of the proposed intervention; (ii) Spanish translation, cross-cultural adaptation and validation of the PREOS-PC survey; (iii) developing the intervention components; and (iv) developing an online tool to electronically administrate PREOS-PC and automatically generate feedback reports to PHC centres. Stage 2 (piloting the intervention) will involve a 3-month feasibility (one group pre-post) study in 10 PHC centres (500 patients, 260 providers). Stage 3 (evaluating the intervention) will involve: (i) a 12-month, two-arm, two-level cluster randomised controlled trial (1248 PHC professionals within 48 PHC centres; with randomisation at the centre level in a 1:1 ratio) to evaluate the impact of the intervention on patient safety culture (primary outcome), patient-reported safety experiences and outcomes (using the PREOS-PC survey), and avoidable hospitalisations; (ii) qualitative study with 20 PHC providers to evaluate the acceptability and perceived utility of the intervention and identify implementation barriers. Ethics and dissemination The study was approved by the Ethics Committee of the Balearic Islands (CEI IB: 3686/18) with the 1964 Helsinki Declaration and its later amendments. The results will be disseminated in peer-reviewed publications and national and international conferences. Trial registration number NCT03837912; pre-results.
Progestogens are the problem in hormone replacement therapy: Time to reappraise their use

Combined (estrogen and a progestogen) hormone replacement therapy (cHRT) is associated with an increased risk of breast cancer, while estrogen replacement therapy is not. Whatever the underlying mechanism, it is the progestogen in cHRT that seems to increase the risk. Fear of breast cancer is a major limiting factor in the use of hormone replacement therapy, and when women discontinue cHRT because of side effects, the latter are often attributable to the progestogen component. cHRT is given to women with an intact uterus to protect against the effects of un-opposed estrogen such as an increased risk of endometrial cancer. Estrogen replacement therapy suffices for women with a prior hysterectomy. There is a clear distinction in risk and side effect profile between cHRT and estrogen replacement therapy. Apart from being the most effective treatment for menopausal symptoms, estrogen prevents osteoporosis, and may also have a potential role in prevention of Alzheimer’s Dementia, now the biggest killer of women in the United Kingdom. Evidence also suggests that progestogens could compromise the dementia-preventative effect of estrogen. Given the immense therapeutic and preventative potential of estrogen, the use of progestogens in cHRT needs re-appraisal. The levonorgestrel intrauterine system (LNg-IUS) could reduce breast cancer risk while protecting the endometrium. Other approaches to the safe use of progestogens await research.
Quinonoid Zwitterion: an Amphiphilic Cathode Interlayer with Initial Thickness-Insensitive and Self-Organizing Properties for Inverted Polymer Solar Cells.

Orthogonal solvent processability is generally considered one of the key requirements for an efficient interfacial material. Here we showed that in inverted polymer solar cells (PSCs), solvent orthogonality is not required for an effective and reliable cathode interlayer. A quinonoid zwitterionic molecule with amphiphilic property (dissolved in both methanol and o-dichlorobenzene (o-DCB)) named ZW-Bu was first applied as the cathode interlayer in the inverted PSCs. For three different photoactive systems, the devices with ZW-Bu CBL exhibited better performance than those with commonly used ZnO CBL. Most importantly, the device efficiency was fairly insensitive to the initial thickness of ZW-Bu. In addition, due to the high surface energy of ZW-Bu film, it was successfully used as self-organized CBL in P3HT:PC61BM system, yielding a desirable efficiency compared to the PSCs fabricated via layer-by-layer deposition method.
A Hybrid Modular DC Solid State Transformer Combining High Efficiency and Control Flexibility

This paper presents a hybrid modular dc solid state transformer (HMDCSST) composed of a series resonant-dual active bridge (SR-DAB) and a phase shift-dual active bridge (PSDAB), aiming at improving the transfer efficiency as well as maintaining the control flexibility. The key problems in terms of modeling and control strategy are discussed in the paper. The generalized average and small signal models of the HMDCSST are derived and confirmed by simulation, in which two LC filters are also considered to reduce the ripple components of the input and output currents. Based on the models, the control strategies to achieve flexible control of the output voltage and power are designed. Moreover, as a key problem for HMDCSST, the design principle of the number for each type of DAB is discussed to meet the demands of the grid. Finally, a three-module prototype of HMDCSST consisting of one PS-DAB and two SR-DAB modules was built-up and tested, and the results proved that HMDCSST has higher efficiency than the traditional DCSST based on PSDABs purely, without sacrificing the output voltage and power regulating capability in the meanwhile.
12 July 2019 VIRTUALLY SPINNING HYPERBOLIC MANIFOLDS

We give a new proof of a result of Sullivan establishing that all finite volume hyperbolic n-manifolds have a finite cover admitting a spin structure. In addition, in all dimensions ≥ 5 we give the first examples of finite volume hyperbolic n-manifolds that do not admit a spin structure.