Miracle-dz/UniFAR-FTUs huggingface dataset:
Missed Down Syndrome Cases after First Trimester False-Negative Screening—Lessons to be Learned

Background and Objectives: Here, we performed a descriptive analysis of Down syndrome (DS) cases that were misdiagnosed and/or false-negative diagnosed after first trimester traditional screening via risk evaluation using ultrasound, biochemical markers, and different software programs. Our objective was to demonstrate the clear need to improve the application of prenatal DS screening programs using standardized ultrasound measurements, accurate pregnancy dating, analytical immunoassay performance, and properly selected medians. Materials and Methods: We performed a database search for the period 2010–2015 to analyze DS cases that were false-negative diagnosed after the first trimester of pregnancy, before the introduction of cell free fetal DNA-based tests by Romanian laboratories in 2015. First-trimester screening was performed using two software programs for prenatal DS risk calculation: Astraia and Prisca. The rationale for using both software programs was to assess the full risk using the maternal age combined test (based on nuchal translucency thickness, nasal bone, ductus venosus flow, tricuspid flow, free beta-human chorionic gonadotropin level, and serum pregnancy-associated plasma protein-A) and, in some cases, the triple test. Results: We identified seven DS cases that exhibited low risk for trisomy 21, and 6540 cases with a low risk for trisomy 21 and euploid fetus in the first trimester. Using Astraia software, 14 cases were diagnosed, and three cases were missed after risk calculation. Using Prisca software, four cases were missed. Additionally, one neonate had a missed prenatal diagnosis of atrio-ventricular canal defect. Conclusion: In Romania, the evaluation of DS risk depends on patient choice (without knowing the accuracy of the utilized tests) and on the operators’ skills. Both Astraia and Prisca software were developed by experts, who can prove their performance in DS screening. However, even in an ideal situation, false-negative results are possible. The application of first and second-trimester combined screening based on biochemical markers could be improved by the implementation of standardized protocols, professional guidelines for test application, and audit control.
The effect of aquatic physical therapy in patients with stroke: A systematic review and meta-analysis

ABSTRACT Objective: The purpose of this study was to evaluate the literature reports of qualitative and quantitative results of physical therapy treatments in the alternative aquatic setting for individuals affected by strokes. Method: PRISMA guidelines were used to carry out the systematic review and meta-analysis. Three bibliographic databases were searched: MEDLINE, PEDro, and the Cochrane Library. Papers included in the study were required to: (a) have a randomized controlled trial (RCT) design of research; and (b) be published in English; (c) be published during the last 10 years (2008–2018). Only randomized controlled trials were employed in the study. The quality of the clinical trials to be included was evaluated according to the Jadad scale. The internal validity was assessed according to the PEDro scale. Results: Eleven RCTs were initially identified in the systematic review. Eight of these were involved in the meta-analysis comparing outcomes and follow-up. Eight studies received a Jadad score of three, indicating a high level of quality. The remaining three studies achieved a lower score which indicated lower qualitative level. Nearly all of the results of the quantitative analysis were statistically significant (P < 0,05) and most of them favored of the experimental group subject to aquatic treatment. Conclusion: Aquatic physical therapy may be a valid means for the rehabilitation of people affected by stroke. The integration of this methodological approach with conventional physical therapy should be considered. However, more studies; a larger number of participants; and varying lengths of follow-up times are necessary.
No Evidence for a Significant Impact of Heterogeneous Chemistry on Radical Concentrations in the North China Plain in Summer 2014

The oxidation of nitric oxide to nitrogen dioxide by hydroperoxy (HO2) and organic peroxy radicals (RO2) is responsible for the chemical net ozone production in the troposphere and for the regeneration of hydroxyl radicals, the most important oxidant in the atmosphere. In Summer 2014, a field campaign was conducted in the North China Plain, where increasingly severe ozone pollution has been experienced in the last years. Chemical conditions in the campaign were representative for this area. Radical and trace gas concentrations were measured, allowing for calculating the turnover rates of gas-phase radical reactions. Therefore, the importance of heterogeneous HO2 uptake on aerosol could be experimentally determined. HO2 uptake could have suppressed ozone formation at that time because of the competition with gas-phase reactions that produce ozone. The successful reduction of the aerosol load in the North China Plain in the last years could have led to a significant decrease of HO2 loss on particles, so that ozone-forming reactions could have gained importance in the last years. However, the analysis of the measured radical budget in this campaign shows that HO2 aerosol uptake did not impact radical chemistry for chemical conditions in 2014. Therefore, reduced HO2 uptake on aerosol since then is likely not the reason for the increasing number of ozone pollution events in the North China Plain, contradicting conclusions made from model calculations reported in the literature.
Cyanidin‐3‐O‐glucoside improves non‐alcoholic fatty liver disease by promoting PINK1‐mediated mitophagy in mice

Identifying safe and effective compounds that target to mitophagy to eliminate impaired mitochondria may be an attractive therapeutic strategy for non‐alcoholic fatty liver disease. Here, we investigated the effects of cyanidin‐3‐O‐glucoside (C3G) on non‐alcoholic fatty liver disease (NAFLD) and the underlying mechanism.
Immunoglobulin expression in the endoplasmic reticulum shapes the metabolic fitness of B lymphocytes

Immunoglobulins shape mitochondrial function by driving ER expansion, this form of metabolic control is independent of the role the immunoglobulins play as part of the antigen receptor on the cell surface. The major function of B lymphocytes is to sense antigens and to produce protective antibodies after activation. This function requires the expression of a B-cell antigen receptor (BCR), and evolutionary conserved mechanisms seem to exist that ensure that B cells without a BCR do not develop nor survive in the periphery. Here, we show that the loss of BCR expression on Burkitt lymphoma cells leads to decreased mitochondrial function and impaired metabolic flexibility. Strikingly, this phenotype does not result from the absence of a classical Syk-dependent BCR signal but rather from compromised ER expansion. We show that the reexpression of immunoglobulins (Ig) in the absence of the BCR signaling subunits Igα and Igβ rescues the observed metabolic defects. We demonstrate that immunoglobulin expression is needed to maintain ER homeostasis not only in lymphoma cells but also in resting B cells. Our study provides evidence that the expression of BCR components, which is sensed in the ER and shapes mitochondrial function, represents a novel mechanism of metabolic control in B cells.
Abdominal Organ Transplantation: Noteworthy Literature in 2019

In the year 2019, we identified and screened over 400 peer-reviewed publications on pancreatic transplantation, over 200 on intestinal transplantation, and over 1900 on kidney transplantation. The liver transplantation section focuses on and features selected articles among 70 clinical trials published in 2019. This review highlights noteworthy literature pertinent to anesthesiologists and critical care physicians caring for patients undergoing abdominal organ transplantation. We explore a broad range of topics, including risks for and prediction of perioperative complications, updated indications for transplantation, recommendations on perioperative management, including Enhanced Recovery After Surgery programs, and topics relevant to optimization of patient and graft outcomes and survival.
Acinetobacter baumannii Resistance: A Real Challenge for Clinicians

Acinetobacter baumannii (named in honor of the American bacteriologists Paul and Linda Baumann) is a Gram-negative, multidrug-resistant (MDR) pathogen that causes nosocomial infections, especially in intensive care units (ICUs) and immunocompromised patients with central venous catheters. A. baumannii has developed a broad spectrum of antimicrobial resistance, associated with a higher mortality rate among infected patients compared with other non-baumannii species. In terms of clinical impact, resistant strains are associated with increases in both in-hospital length of stay and mortality. A. baumannii can cause a variety of infections; most involve the respiratory tract, especially ventilator-associated pneumonia, but bacteremia and skin wound infections have also been reported, the latter of which has been prominently observed in the context of war-related trauma. Cases of meningitis associated with A. baumannii have been documented. The most common risk factor for the acquisition of MDR A baumannii is previous antibiotic use, following by mechanical ventilation, length of ICU/hospital stay, severity of illness, and use of medical devices. Current efforts focus on addressing all the antimicrobial resistance mechanisms described in A. baumannii, with the objective of identifying the most promising therapeutic scheme. Bacteriophage- and artilysin-based therapeutic approaches have been described as effective, but further research into their clinical use is required
Non-Apoptotic Cell Death Signaling Pathways in Melanoma

Resisting cell death is a hallmark of cancer. Disturbances in the execution of cell death programs promote carcinogenesis and survival of cancer cells under unfavorable conditions, including exposition to anti-cancer therapies. Specific modalities of regulated cell death (RCD) have been classified based on different criteria, including morphological features, biochemical alterations and immunological consequences. Although melanoma cells are broadly equipped with the anti-apoptotic machinery and recurrent genetic alterations in the components of the RAS/RAF/MEK/ERK signaling markedly contribute to the pro-survival phenotype of melanoma, the roles of autophagy-dependent cell death, necroptosis, ferroptosis, pyroptosis, and parthanatos have recently gained great interest. These signaling cascades are involved in melanoma cell response and resistance to the therapeutics used in the clinic, including inhibitors of BRAFmut and MEK1/2, and immunotherapy. In addition, the relationships between sensitivity to non-apoptotic cell death routes and specific cell phenotypes have been demonstrated, suggesting that plasticity of melanoma cells can be exploited to modulate response of these cells to different cell death stimuli. In this review, the current knowledge on the non-apoptotic cell death signaling pathways in melanoma cell biology and response to anti-cancer drugs has been discussed.
An Inverse Approach for Ultrasonic Imaging From Full Matrix Capture Data: Application to Resolution Enhancement in NDT

In the context of nondestructive testing (NDT), this article proposes an inverse problem approach for the reconstruction of high-resolution ultrasonic images from full matrix capture (FMC) data sets. We build a linear model that links the FMC data, i.e., the signals collected from all transmitter–receiver pairs of an ultrasonic array, to the discretized reflectivity map of the inspected object. In particular, this model includes the ultrasonic waveform corresponding to the response of transducers. Despite a large amount of data, the inversion problem is ill-posed. Therefore, a regularization strategy is proposed, where the reconstructed image is defined as the minimizer of a penalized least-squares cost function. A mixed penalization function is considered, which simultaneously enhances the sparsity of the image (in NDT, the reflectivity map is mostly zero except at the flaw locations) and its spatial smoothness (flaws may have some spatial extension). The proposed method is shown to outperform two well-known imaging methods: the total focusing method (TFM) and Excitelet. Numerical simulations with two close reflectors show that the proposed method improves the resolution limit defined by the Rayleigh criterion by a factor of four. Such high-resolution imaging capability is confirmed by experimental results obtained with side-drilled holes in an aluminum sample.
RNA-Targeted Therapies and High-Throughput Screening Methods

RNA-binding proteins (RBPs) are involved in regulating all aspects of RNA metabolism, including processing, transport, translation, and degradation. Dysregulation of RNA metabolism is linked to a plethora of diseases, such as cancer, neurodegenerative diseases, and neuromuscular disorders. Recent years have seen a dramatic shift in the knowledge base, with RNA increasingly being recognised as an attractive target for precision medicine therapies. In this article, we are going to review current RNA-targeted therapies. Furthermore, we will scrutinise a range of drug discoveries targeting protein-RNA interactions. In particular, we will focus on the interplay between Lin28 and let-7, splicing regulatory proteins and survival motor neuron (SMN) pre-mRNA, as well as HuR, Musashi, proteins and their RNA targets. We will highlight the mechanisms RBPs utilise to modulate RNA metabolism and discuss current high-throughput screening strategies. This review provides evidence that we are entering a new era of RNA-targeted medicine.
Clinical phenotypes of SARS-CoV-2: implications for clinicians and researchers

Patients with COVID-19 present a broad spectrum of clinical presentation. Whereas hypoxaemia is the marker of severity, different strategies of management should be customised to five specific individual phenotypes. Many intubated patients present with phenotype 4, characterised by pulmonary hypoxic vasoconstriction, being associated with severe hypoxaemia with “normal” (>40 mL·cmH2O−1) lung compliance and likely representing pulmonary microvascular thrombosis. Phenotype 5 is often associated with high plasma procalcitonin and has low pulmonary compliance, Which is a result of co-infection or acute lung injury after noninvasive ventilation. Identifying these clinical phenotypes and applying a personalised approach would benefit the optimisation of therapies and improve outcomes. SARS-CoV-2 infections present different specific individual phenotypes. Applying a personalised approach would benefit in optimisation of therapies and outcome improvement. #COVID19 https://bit.ly/3akTSuf
Development and In Vitro and In Vivo Evaluation of Microspheres Containing Sodium N-[8-(2-hydroxybenzoyl)amino]caprylate for the Oral Delivery of Berberine Hydrochloride

Microspheres containing absorption enhancer (sodium N-[8-(2-hydroxybenzoyl)amino]caprylate, SNAC) were developed to enhance the oral bioavailability of berberine hydrochloride (BER) with poor intestinal membrane permeability. Microspheres were prepared and characterized by particle size measurements, scanning electron microscopy, differential scanning calorimetry, BER payload and release, Caco-2 cell monolayer transport, and rat pharmacokinetics. The microspheres were spherical and had uniform size, high encapsulation efficiency and high loading capacity. In vitro release studies showed that BER-loaded microspheres had good sustained release characteristics. The Caco-2 cell monolayer transport study proved that SNAC could significantly enhance permeability of BER 2–3-fold. Pharmacokinetic studies demonstrated a 9.87-fold increase in area under the curve (AUC) of BER mixed with SNAC and a 14.14-fold increase in AUC of microspheres compared with BER alone. These findings indicate that SNAC is a promising absorption enhancer for oral delivery of BER in the form of both solution and microspheres.
Experimentally Engineered Mutations in a Ubiquitin Hydrolase, UBP-1, Modulate In Vivo Susceptibility to Artemisinin and Chloroquine in Plasmodium berghei

As resistance to artemisinins (current frontline drugs in malaria treatment) emerges in Southeast Asia, there is an urgent need to identify the genetic determinants and understand the molecular mechanisms underpinning such resistance. Such insights could lead to prospective interventions to contain resistance and prevent the eventual spread to other regions where malaria is endemic. Reduced susceptibility to artemisinin in Southeast Asia has been primarily linked to mutations in the Plasmodium falciparum Kelch-13 gene, which is currently widely recognized as a molecular marker of artemisinin resistance. ABSTRACT As resistance to artemisinins (current frontline drugs in malaria treatment) emerges in Southeast Asia, there is an urgent need to identify the genetic determinants and understand the molecular mechanisms underpinning such resistance. Such insights could lead to prospective interventions to contain resistance and prevent the eventual spread to other regions where malaria is endemic. Reduced susceptibility to artemisinin in Southeast Asia has been primarily linked to mutations in the Plasmodium falciparum Kelch-13 gene, which is currently widely recognized as a molecular marker of artemisinin resistance. However, two mutations in a ubiquitin hydrolase, UBP-1, have been previously associated with reduced artemisinin susceptibility in a rodent model of malaria, and some cases of UBP-1 mutation variants associated with artemisinin treatment failure have been reported in Africa and SEA. In this study, we employed CRISPR-Cas9 genome editing and preemptive drug pressures to test these artemisinin susceptibility-associated mutations in UBP-1 in Plasmodium berghei sensitive lines in vivo. Using these approaches, we show that the V2721F UBP-1 mutation results in reduced artemisinin susceptibility, while the V2752F mutation results in resistance to chloroquine (CQ) and moderately impacts tolerance to artemisinins. Genetic reversal of the V2752F mutation restored chloroquine sensitivity in these mutant lines, whereas simultaneous introduction of both mutations could not be achieved and appears to be lethal. Interestingly, these mutations carry a detrimental growth defect, which would possibly explain their lack of expansion in natural infection settings. Our work provides independent experimental evidence on the role of UBP-1 in modulating parasite responses to artemisinin and chloroquine under in vivo conditions.
Interaction of landscape varibles on the potential geographical distribution of parrots in the Yucatan Peninsula, Mexico

La interaccion de las variables del paisaje en la distribucion geografica potencial de los loros en la peninsula de Yucatan, Mexico La perdida, degradacion y fragmentacion de las zonas boscosas estan poniendo en peligro a las poblaciones de loros. En este estudio se determino la influencia de la fragmentacion en relacion con la cobertura vegetal, los usos del suelo y la configuracion espacial de los fragmentos, sobre los modelos de distribucion geografica potencial de los loros en la peninsula de Yucatan, Mexico. Se utilizo la distribucion geografica potencial de ocho especies de loros, teniendo en cuenta los mapas publicados recientemente y obtenidos con el algoritmo de maxima entropia, y se incorporo el mapa de probabilidad de distribucion de cada especie. Se calcularon 71 parametros y variables que evaluan la fragmentacion forestal, la configuracion espacial de los fragmentos, la proporcion ocupada por vegetacion y los usos del suelo en 100 parcelas de aproximadamente 29 km² distribuidas al azar dentro de las zonas de presencia y ausencia predichas para cada especie. Ademas, se tuvo en cuenta la relacion entre las variables ambientales y la probabilidad de distribucion de las especies. Se empleo una regresion de minimos cuadrados parciales para analizar la relacion existente entre las variables empleadas y los modelos de distribucion potencial. Ninguna de las variables ambientales analizadas determina por si sola la presencia, la ausencia ni la probabilidad de distribucion de los loros en la peninsula. Se observo que para las ocho especies, ya sea debido a la presencia y la ausencia o a la probabilidad de distribucion, las variables explicativas mas importantes son la interaccion entre tres variables, en especial la interaccion entre la superficie forestal total, la longitud total de los perimetros de los fragmentos y la cantidad de bosque tropical subperennifolio de altura mediana. La fragmentacion del habitat influye sobre la distribucion geografica potencial de estas especies en combinacion con otros factores ambientales asociados a la misma, como son la proporcion de las diferentes coberturas vegetales y los usos del suelo que se desarrollan en las areas deforestadas.
Sperm Cell Driven Microrobots—Emerging Opportunities and Challenges for Biologically Inspired Robotic Design

With the advent of small-scale robotics, several exciting new applications like Targeted Drug Delivery, single cell manipulation and so forth, are being discussed. However, some challenges remain to be overcome before any such technology becomes medically usable; among which propulsion and biocompatibility are the main challenges. Propulsion at micro-scale where the Reynolds number is very low is difficult. To overcome this, nature has developed flagella which have evolved over millions of years to work as a micromotor. Among the microscopic cells that exhibit this mode of propulsion, sperm cells are considered to be fast paced. Here, we give a brief review of the state-of-the-art of Spermbots—a new class of microrobots created by coupling sperm cells to mechanical loads. Spermbots utilize the flagellar movement of the sperm cells for propulsion and as such do not require any toxic fuel in their environment. They are also naturally biocompatible and show considerable speed of motion thereby giving us an option to overcome the two challenges of propulsion and biocompatibility. The coupling mechanisms of physical load to the sperm cells are discussed along with the advantages and challenges associated with the spermbot. A few most promising applications of spermbots are also discussed in detail. A brief discussion of the future outlook of this extremely promising category of microrobots is given at the end.