Miracle-dz/UniFAR-FTUs huggingface dataset:
Concussive Symptoms Following Pediatric Mild Traumatic Brain Injury

Objectives: To determine the proportion of children with postconcussive symptoms (PCSs) and to explore the influence of noninjury and injury factors on parents' PCS report at 3 months postinjury. Design: A cross-sectional analysis of the 3-month postinjury data from a larger, prospective, longitudinal study. Methods: Parents and their child aged 2 to 12 years who presented at the emergency department with either a mild traumatic brain injury (mTBI) or a superficial injury to the head (SIH) were recruited. Parents reported their child's symptoms at the time of injury and at 3 months postinjury. Child, family/parent, and injury characteristics were considered as potential predictors. Logistic regression was conducted to determine which factors increase the likelihood of parents' PCS report. Results: At 3 months postinjury, 30% and 13% of children in the mTBI and SIH groups exhibited 1 or more symptoms, respectively. On the other hand, 18% (mTBI) and 8% (SIH) continued to have ongoing problems when 2 or more symptoms were considered at follow-up. The final model, which included child's sex, injury group, number of symptoms at the time of injury, and parental stress, had a significant predictive utility in determining parents' report of 1 or more symptoms at follow-up. Only parental stress continued to be a significant predictor when considering 2 or more symptoms at 3 months postinjury. Conclusions: Children with mTBI have worse outcomes than children with SIH at follow-up, with parents more likely to report 1 or more ongoing symptoms if their children had an mTBI. Postinjury assessment of parental stress and ongoing symptom monitoring in young children with mTBI will allow for timely provision of support for the family.
Does tumor stroma ratio of breast cancer trucut biopsy determine response to neoadjuvant therapy?

Aims and Objectives: We examined the prognostic value of Tumor stroma ratio (TSR) in breast tumor core biopsy (TCB) specimen to determine response to neoadjuvant therapy (NAT) prior to modified radical mastectomy (MRM). Methods: This was a retrospective analysis of patients with breast cancer who underwent TCB before NAT between August 2016 and July 2018. TSR in TCB was studied independently by 2 pathologists ( VM, VS) defined as stroma rich (TSR≤50%) or stroma poor (TSR>50%). MRM specimen of these patients were subsequently studied . Residual cancer burden (RCB) was calculated using the MD Anderson RCB calculator, categorized as complete (0), good (1) Partial (2) and no response (3). Statistical analysis was done to assess correlation of TSR to RCB. Results: A total of 62 patients were analyzed. Mean(SD) age was 48(11) years.Twenty eight (45%) and 34 (55%) patients were stroma rich and stroma poor respectively. Twenty six (42%) patients were responders and 36 (58%) non-responders to NAT. Among stroma rich patients, only 3 (10%) were responders (Class 0 &1)and 25 (90%) non-responders(Class2&3)to NAT, among stroma poor patients 23 (68%) responded well and 11 (32%) did not.TSR had a moderate negative correlation with RCB (-0.6). On univariate analysis, only TSR had a significant effect on RCB class (<0.001). Conclusions: TSR on TCB is a useful prognostic factor to determine response of breast carcinoma patients to neoadjuvant therapy.It is cost effective, simple and quick. Larger multi-centric studies would be useful to study its clinical implications.
The Evolution History of Fe–S Cluster A-Type Assembly Protein Reveals Multiple Gene Duplication Events and Essential Protein Motifs

Abstract Iron–sulfur (Fe–S) clusters play important roles in electron transfer, metabolic and biosynthetic reactions, and the regulation of gene expression. Understanding the biogenesis of Fe–S clusters is therefore relevant to many fields. In the complex process of Fe–S protein formation, the A-type assembly protein (ATAP) family, which consists of several subfamilies, plays an essential role in Fe–S cluster formation and transfer and is highly conserved across the tree of life. However, the taxonomic distribution, motif compositions, and the evolutionary history of the ATAP subfamilies are not well understood. To address these problems, our study investigated the taxonomic distribution of 321 species from a broad cross-section of taxa. Then, we identified common and specific motifs in multiple ATAP subfamilies to explain the functional conservation and nonredundancy of the ATAPs, and a novel, essential motif was found in Eumetazoa IscA1, which has a newly found magnetic function. Finally, we used phylogenetic analytical methods to reconstruct the evolution history of this family. Our results show that two types of ErpA proteins (nonproteobacteria-type ErpA1 and proteobacteria-type ErpA2) exist in bacteria. The ATAP family, consisting of seven subfamilies, can be further classified into two types of ATAPs. Type-I ATAPs include IscA, SufA, HesB, ErpA1, and IscA1, with an ErpA1-like gene as their last common ancestor, whereas type-II ATAPs consist of ErpA2 and IscA2, duplicated from an ErpA2-like gene. During the mitochondrial endosymbiosis, IscA became IscA1 in eukaryotes and ErpA2 became IscA2 in eukaryotes, respectively.
Lower Success Rate of Débridement and Implant Retention in Late Acute versus Early Acute Periprosthetic Joint Infection Caused by Staphylococcus spp. Results from a Matched Cohort Study.

BACKGROUND Surgical débridement, antibiotics and implant retention (DAIR) is currently recommended by international guidelines for both early acute (postsurgical) and late acute (hematogenous) periprosthetic joint infections (PJIs). However, due to a different pathogenesis of infection, a different treatment strategy may be needed. QUESTIONS/PURPOSES (1) Compared with early acute PJIs, are late acute PJIs associated with a higher risk of DAIR failure? (2) When stratified by microorganism, is the higher risk of failure in late acute PJI associated with Staphylocococcus aureus infection? (3) When analyzing patients with S. aureus infection, what factors are independently associated with DAIR failure? METHODS In this multicenter observational study, early acute and late acute PJIs treated with DAIR were retrospectively evaluated and matched according to treating center, year of diagnosis, and infection-causing microorganism. If multiple matches were available, the early acute PJI diagnosed closest to the late acute PJI was selected. A total of 132 pairs were included. Treatment success was defined as a retained implant during follow-up without the need for antibiotic suppressive therapy. RESULTS Late acute PJIs had a lower treatment success (46% [60 of 132]) compared with early acute PJIs (76% [100 of 132]), OR 3.9 [95% CI 2.3 to 6.6]; p < 0.001), but the lower treatment success of late acute PJIs was only observed when caused by Staphylococcus spp (S. aureus: 34% versus 75%; p < 0.001; coagulase-negative staphylococci: 46% versus 88%; p = 0.013, respectively). On multivariable analysis, late acute PJI was the only independent factor associated with an unsuccessful DAIR when caused by S. aureus (OR 4.52 [95% CI 1.79 to 11.41]; p < 0.001). CONCLUSIONS Although DAIR seems to be a successful therapeutic strategy in the management of early acute PJI, its use in late acute PJI should be reconsidered when caused by Staphylococcus spp. Our results advocate the importance of isolating the causative microorganism before surgery. LEVEL OF EVIDENCE Level III, therapeutic study.
Dietary lysophospholipids supplementation inhibited the activity of lipolytic bacteria in forage with high oil diet: an in vitro study

Objective The objective of this study was to evaluate the effects of lysophospholipids (LPL) supplementation on rumen fermentation, degradability, and microbial diversity in forage with high oil diet in an in vitro system. Methods Four experimental treatments were used: i) annual ryegrass (CON), ii) 93% annual ryegrass +7% corn oil on a dry matter (DM) basis (OiL), iii) OiL with a low level (0.08% of dietary DM) of LPL (LLPL), and iv) OiL with a high level (0.16% of dietary DM) of LPL (HLPL). An in vitro fermentation experiment was performed using strained rumen fluid for 48 h incubations. In vitro DM degradability (IVDMD), in vitro neutral detergent fiber degradability, pH, ammonia nitrogen (NH3-N), volatile fatty acid (VFA), and microbial diversity were estimated. Results There was no significant change in IVDMD, pH, NH3-N, and total VFA production among treatments. The LPL supplementation significantly increased the proportion of butyrate and valerate (Linear effect [Lin], p = 0.004 and <0.001, respectively). The LPL supplementation tended to increase the total bacteria in a linear manner (p = 0.089). There were significant decreases in the relative proportions of cellulolytic (Fibrobacter succinogenes and Ruminococcus albus) and lipolytic (Anaerovibrio lipolytica and Butyrivibrio proteoclasticus) bacteria with increasing levels of LPL supplementation (Lin, p = 0.028, 0.006, 0.003, and 0.003, respectively). Conclusion The LPL supplementation had antimicrobial effects on several cellulolytic and lipolytic bacteria, with no significant difference in nutrient degradability (DM and neutral detergent fiber) and general bacterial counts, suggesting that LPL supplementation might increase the enzymatic activity of rumen bacteria. Therefore, LPL supplementation may be more effective as an antimicrobial agent rather than as an emulsifier in the rumen.
Spatiotemporal signal detection using continuous shrinkage priors

Periodontal disease (PD) is a chronic inflammatory disease that affects the gum tissue and bone supporting the teeth. Although tooth‐site level PD progression is believed to be spatio‐temporally referenced, the whole‐mouth average periodontal pocket depth (PPD) has been commonly used as an indicator of the current/active status of PD. This leads to imminent loss of information, and imprecise parameter estimates. Despite availability of statistical methods that accommodates spatiotemporal information for responses collected at the tooth‐site level, the enormity of longitudinal databases derived from oral health practice‐based settings render them unscalable for application. To mitigate this, we introduce a Bayesian spatiotemporal model to detect problematic/diseased tooth‐sites dynamically inside the mouth for any subject obtained from large databases. This is achieved via a spatial continuous sparsity‐inducing shrinkage prior on spatially varying linear‐trend regression coefficients. A low‐rank representation captures the nonstationary covariance structure of the PPD outcomes, and facilitates the relevant Markov chain Monte Carlo computing steps applicable to thousands of study subjects. Application of our method to both simulated data and to a rich database of electronic dental records from the HealthPartners ® Institute reveal improved prediction performances, compared with alternative models with usual Gaussian priors for regression parameters and conditionally autoregressive specification of the covariance structure.
Expanding the Noonan spectrum/RASopathy NGS panel: Benefits of adding NF1 and SPRED1

RASopathies are a group of disorders caused by disruptions to the RAS‒MAPK pathway. Despite being in the same pathway, Neurofibromatosis Type 1 (NF1) and Legius syndrome (LS) typically present with phenotypes distinct from Noonan spectrum disorders (NSDs). However, some NF1/LS individuals also exhibit NSD phenotypes, often referred to as Neurofibromatosis‐Noonan syndrome (NFNS), and may be mistakenly evaluated for NSDs, delaying diagnosis, and affecting patient management.
Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes.

Citation: Pietro Merli, Lorenza Putignani, Annalisa Ruggeri, Federica Del Chierico, Livia Gargiullo, Federica Galaverna, Stefania Gaspari, Daria Pagliara, Alessandra Russo, Stefania Pane, Luisa Strocchio, Mattia Algeri, Francesca Rea, Erminia Francesca Romeo, Paola Bernaschi, Andrea Onetti Muda, Bruno Dallapiccola, and Franco Locatelli. Decolonization of multi-drug resistant bacteria by fecal microbiota transplantation in five pediatric patients before allogeneic hematopoietic stem cell transplantation: gut microbiota profiling, infectious and clinical outcomes. Haematologica. 2020; 105:xxx doi:10.3324/haematol.2019. 244210
Health-related quality of life in older Chinese patients with diabetes

Background Although older diabetes patients with unique characteristics should be cared carefully to improve their health-related quality of life (HRQOL), the association between diabetes and HRQOL remain unclear, especially in Asians. We aimed to compare the HRQOL between older Chinese patients with type 2 diabetes (T2D) and their age-gender-matched controls. Methods Older patients with T2D were recruited from a community hospital in Suzhou located in the east part of China while controls were selected from a community-based health survey of older adults aged 60 years or older. HRQOL of cases and controls was assessed by the EQ-5D-3L. The impact of T2D on HRQOL was investigated using a liner regression model and the relationship between T2D and EQ-5D health problems was evaluated using logistic regression models. Results A total of 220 cases and 440 controls were included. The mean age of the participants was 68.8 years and women accounted for 69.1% of the study sample. The EQ-5D-3L index score was lower for older people with T2D (0.886) than their controls (0.955). After multivariable adjustment, the difference in ED-5D-3L index score between older people with and without T2D was 0.072. In logistic regression analyses, T2D was positively associated with reporting of problems in mobility (odds ratio [OR] = 5.00); pain/discomfort (OR = 1.66), and anxiety/depression (OR = 3.2). Conclusions T2D has a detrimental effect on HRQOL of older Chinese people.
Dental disease in alpacas. Part 1: Prevalence of dental disorders and their mutual relationships

Abstract Background Dental disease is a troublesome health concern in alpacas. Specifically, the occurrence of tooth root abscesses has been described in veterinary literature. Nevertheless, no objective prevalence data are available for dental disorders in alpacas. Hypothesis/objectives To determine the prevalence of dental disorders in alpaca herds in Belgium and the Netherlands. To study the associations between the different dental disorders encountered in alpacas. Animals A total of 228 alpacas (Vicugna pacos) originating from 25 farms. Methods This is a cross‐sectional study. Dental disorders were diagnosed by dental examination of sedated animals using a dental mirror or a portable rigid oroscope. Results At the animal level, 82% (n = 187) had dental disorders of which 74.6, 41.7, and 3.9% were cheek teeth, incisor disorders, and canine disorders, respectively. At the level of the cheek teeth, diastemata (43.1%) were most common, followed by wear abnormalities (WA; 39.6%) and periodontal disease (PD; 33.3%). A significant association was detected between the presence of diastemata and PD (odds ratio [OR], 13.1; 95% confidence interval [CI], 6.6‐27.7; P < .001). Pulp exposure was significantly associated with the presence of diastemata (OR, 11.8; 95% CI, 3.8‐51.5; P < .001), PD (OR, 8.2; 95% CI, 3.1‐25.3; P < .001) and WA (OR, 2.9; 95% CI, 1.2‐7.4; P = .002). Conclusion and Clinical Importance Dental disorders are highly prevalent in alpacas in Belgium and the Netherlands. Several dental disorders in alpacas had significant associations. To prevent the development of advanced stages of dental disease, routine dental examinations are advised to allow early detection and prompt treatment.
Exploiting Preexisting Immunity to Enhance Oncolytic Cancer Immunotherapy

These findings establish a novel technology that enhances oncolytic cancer immunotherapy by capitalizing on pre-acquired immunity to pathogens to convert a weak antitumor immune response into a much stronger one. Because of the high coverage of international vaccination programs, most people worldwide have been vaccinated against common pathogens, leading to acquired pathogen-specific immunity with a robust memory T-cell repertoire. Although CD8+ antitumor cytotoxic T lymphocytes (CTL) are the preferred effectors of cancer immunotherapy, CD4+ T-cell help is also required for an optimal antitumor immune response to occur. Hence, we investigated whether the pathogen-related CD4+ T-cell memory populations could be reengaged to support the CTLs, converting a weak primary antitumor immune response into a stronger secondary one. To this end, we used our PeptiCRAd technology that consists of an oncolytic adenovirus coated with MHC-I–restricted tumor-specific peptides and developed it further by introducing pathogen-specific MHC-II–restricted peptides. Mice preimmunized with tetanus vaccine were challenged with B16.OVA tumors and treated with the newly developed hybrid TT-OVA-PeptiCRAd containing both tetanus toxoid- and tumor-specific peptides. Treatment with the hybrid PeptiCRAd significantly enhanced antitumor efficacy and induced TT-specific, CD40 ligand-expressing CD4+ T helper cells and maturation of antigen-presenting cells. Importantly, this approach could be extended to naturally occurring tumor peptides (both tumor-associated antigens and neoantigens), as well as to other pathogens beyond tetanus, highlighting the usefulness of this technique to take full advantage of CD4+ memory T-cell repertoires when designing immunotherapeutic treatment regimens. Finally, the antitumor effect was even more prominent when combined with the immune checkpoint inhibitor anti–PD-1, strengthening the rationale behind combination therapy with oncolytic viruses. Significance: These findings establish a novel technology that enhances oncolytic cancer immunotherapy by capitalizing on pre-acquired immunity to pathogens to convert a weak antitumor immune response into a much stronger one.
Soluble vascular endothelial-cadherin in CSF after subarachnoid hemorrhage

Objective To determine if CSF and plasma levels of soluble vascular endothelial (sVE)-cadherin are associated with functional outcome after subarachnoid hemorrhage (SAH) and to investigate sVE-cadherin effects on microglia. Methods Serial CSF and plasma were collected from prospectively enrolled patients with nontraumatic SAH from a ruptured aneurysm in the anterior circulation and who required an external ventricular drain for clinical indications. Patients with normal-pressure hydrocephalus without SAH served as controls. For prospective assessment of long-term outcomes at 3 and 6 months after SAH, modified Rankin Scale scores (mRS) were obtained and dichotomized into good (mRS ≤ 2) vs poor (mRS > 2) outcome groups. For SAH severity, Hunt and Hess grade was assessed. Association of CSF sVE-cadherin levels with long-term outcomes, HH grade, and CSF tumor necrosis factor (TNF)-α levels were evaluated. sVE-cadherin effects on microglia were also studied. Results sVE-cadherin levels in CSF, but not in plasma, were higher in patients with SAH and were associated with higher clinical severity and higher CSF TNF-α levels. Patients with SAH with higher CSF sVE-cadherin levels over time were more likely to develop worse functional outcome at 3 months after SAH. Incubation of cultured microglia with sVE-cadherin resulted in increased inducible nitric oxide synthase, interleukin-1β, reactive oxygen species, cell soma size, and metabolic activity, consistent with microglia activation. Microinjection of sVE-cadherin fragments into mouse brain results in an increased number of microglia surrounding the injection site, compared to injection of denatured vascular endothelial–cadherin fragments. Conclusions These results support the existence of a novel pathway by which sVE-cadherin, released from injured endothelium after SAH, can shift microglia into a more proinflammatory phenotype and contribute to neuroinflammation and poor outcome in SAH.
Termination of non‐coding transcription in yeast relies on both an RNA Pol II CTD interaction domain and a CTD‐mimicking region in Sen1

Pervasive transcription is a widespread phenomenon leading to the production of a plethora of non‐coding RNAs (ncRNAs) without apparent function. Pervasive transcription poses a threat to proper gene expression that needs to be controlled. In yeast, the highly conserved helicase Sen1 restricts pervasive transcription by inducing termination of non‐coding transcription. However, the mechanisms underlying the specific function of Sen1 at ncRNAs are poorly understood. Here, we identify a motif in an intrinsically disordered region of Sen1 that mimics the phosphorylated carboxy‐terminal domain (CTD) of RNA polymerase II, and structurally characterize its recognition by the CTD‐interacting domain of Nrd1, an RNA‐binding protein that binds specific sequences in ncRNAs. In addition, we show that Sen1‐dependent termination strictly requires CTD recognition by the N‐terminal domain of Sen1. We provide evidence that the Sen1‐CTD interaction does not promote initial Sen1 recruitment, but rather enhances Sen1 capacity to induce the release of paused RNAPII from the DNA. Our results shed light on the network of protein–protein interactions that control termination of non‐coding transcription by Sen1.
Deep Learning Techniques for Diabetic Retinopathy Detection.

Diabetes occurs due to the excess of glucose in the blood that may affect many organs of the body. The increase in blood sugar in the body causes many problems. One of the most prominent of these problems is Diabetic Retinopathy (DR). DR occurs due to the mutilation of the blood vessels in a retina. The detection of DR is complicated and time-consuming due to its features for the ophthalmologists. Therefore, automatic detection is required, recently different machine and deep learning techniques are being applied to detect and classify DR. In this paper, we conducted a study of the various techniques available in the literature for the identification/classification of DR, the datasets used, strengths and weaknesses of each method and provides the future directions. Moreover, we also discussed the different steps for the detection that are segmentation of blood vessels in a retina, detecting lesions and other abnormalities of DR in binary and multiclass classification.
Near-infrared spectroscopy-derived total haemoglobin as an indicator of changes in muscle blood flow during exercise-induced hyperaemia

ABSTRACT Blood flow changes in response to exercise have been attributed, among other factors, to the effect of vasodilators factors on the microvasculature, suggesting a close relationship between small blood vessels and conducting arteries. The main purpose of this study was to determine the relationship between the changes in near infrared spectroscopy (NIRS)-derived total haemoglobin ([tHb]) and muscle oxygen saturation (SmO2) signals and femoral artery blood flow in response to resistance exercise at fast- and slow-velocity muscle contraction. The study randomised crossover design included twelve participants. NIRS and blood flow measurements were continuously monitored before, during, and 5 min after the exercise protocol. There was a significant correlation between [tHb] reperfusion slope ([tHb]slope) and peak blood flow (BFpeak) after slow- and fast-velocity muscle contraction (r = 0.83, p = 0.0008 and r = 0.72, p = 0.0080, respectively). No significant correlation existed between the SmO2 reperfusion slope (SmO2_slope) and BFpeak after both slow- and fast-velocity muscle contraction exercise (r = −0.46, p = 0.1253 and r = 0.33, p = 0.2841, respectively). This study demonstrated a strong relationship between the NIRS-derived [tHb] and Doppler ultrasound BF during the recovery period of dynamic resistance exercise at both slow- and fast-velocity contraction.