Miracle-dz/UniFAR-FTUs huggingface dataset:
Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial

BACKGROUND Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours. METHODS In this controlled, open-label, phase 2/3 trial, we randomly assigned 716 patients with histologically-confirmed advanced clinical stage cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant metastases, via central interactive web-based-response system, to receive either three pre-operative and three postoperative 3-week cycles of 50 mg/m2 epirubicin and 60 mg/m2 cisplatin on day 1 plus either 200 mg/m2 fluorouracil as continuous intravenous infusion or 1250 mg/m2 capecitabine orally on days 1 to 21 (ECF/ECX; control group) or four preoperative and four postoperative 2-week cycles of 50 mg/m2 docetaxel, 85 mg/m2 oxaliplatin, 200 mg/m2 leucovorin and 2600 mg/m2 fluorouracil as 24-h infusion on day 1 (FLOT; experimental group). The primary outcome of the trial was overall survival (superiority) analysed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01216644. FINDINGS Between Aug 8, 2010, and Feb 10, 2015, 716 patients were randomly assigned to treatment in 38 German hospitals or with practice-based oncologists. 360 patients were assigned to ECF/ECX and 356 patients to FLOT. Overall survival was increased in the FLOT group compared with the ECF/ECX group (hazard ratio [HR] 0·77; 95% confidence interval [CI; 0.63 to 0·94]; median overall survival, 50 months [38·33 to not reached] vs 35 months [27·35 to 46·26]). The number of patients with related serious adverse events (including those occurring during hospital stay for surgery) was similar in the two groups (96 [27%] in the ECF/ECX group vs 97 [27%] in the FLOT group), as was the number of toxic deaths (two [<1%] in both groups). Hospitalisation for toxicity occurred in 94 patients (26%) in the ECF/ECX group and 89 patients (25%) in the FLOT group. INTERPRETATION In locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma, perioperative FLOT improved overall survival compared with perioperative ECF/ECX. FUNDING The German Cancer Aid (Deutsche Krebshilfe), Sanofi-Aventis, Chugai, and Stiftung Leben mit Krebs Foundation.
Ocular surface evaluation in pediatric Hashimoto's thyroiditis without thyroid-associated ophthalmopathy.

PURPOSE We aimed to assess ocular surface characteristics in children with Hashimoto's thyroiditis without thyroid-associated ophthalmopathy and compare the results with those of healthy children. METHODS Twenty-two children with Hashimoto's thyroiditis (Group 1) and 20 healthy children without any ocular and/or systemic disorder (Group 2) were enrolled in the study. Ocular Surface Disease Index questionnaire, tear film osmolarity measurement (TearLab Osmolarity System, San Diego, CA, USA), Schirmer and tear film breakup time tests, meibography, and conjunctival brush cytology were performed and compared the results between the groups. RESULTS The study group included 19 girls and 3 boys in Group 1 and 12 girls and 8 boys in Group 2 (p=0.081). Thyroid-associated ophthalmopathy was not identified in any of the patients. Mean tear film osmolarity was 310.23 ± 11.98 mOsm/l in Group 1 and 313.60 ± 15.03 mOsm/l in Group 2 (p=0.424). Mean Schirmer test score was lower in Group 1 (14.91 ± 6.27) compared with Group 2 (23.60 ± 5.63) (p=0.001). Mean tear film breakup time was lower in Group 1 (11.78 ± 4.07) compared with Group 2 (15.1 ± 1.6) (p=0.013). Moreover, mean meibomian gland area loss was 25.01% ± 10.04% in Group 1 and 16.54% ± 6.02% in Group 2 (p=0.002). Conjunctival cytologic analysis in Group 1 revealed grade 0 changes in 6 patients (27.3%), grade 1 changes in 14 patients (63.6%), and grade 2 changes in 2 patients (9.1%), whereas 18 patients (90%) had grade 0 changes and 2 patients (10%) had grade 1 changes (p=0.001) in Group 2. CONCLUSIONS The study demonstrates several ocular surface changes in children with Hashimoto's thyroiditis. These findings may indicate a tendency for dry eye in pediatric Hashimoto's thyroiditis patients without clinical evidence of thyroid-associated ophthalmopathy.
Response Modifiers: Tweaking the Immune Response Against Influenza A Virus

Despite causing pandemics and yearly epidemics that result in significant morbidity and mortality, our arsenal of options to treat influenza A virus (IAV) infections remains limited and is challenged by the virus itself. While vaccination is the preferred intervention strategy against influenza, its efficacy is reduced in the elderly and infants who are most susceptible to severe and/or fatal infections. In addition, antigenic variation of IAV complicates the production of efficacious vaccines. Similarly, effectiveness of currently used antiviral drugs is jeopardized by the development of resistance to these drugs. Like many viruses, IAV is reliant on host factors and signaling-pathways for its replication, which could potentially offer alternative options to treat infections. While host-factors have long been recognized as attractive therapeutic candidates against other viruses, only recently they have been targeted for development as IAV antivirals. Future strategies to combat IAV infections will most likely include approaches that alter host-virus interactions on the one hand or dampen harmful host immune responses on the other, with the use of biological response modifiers (BRMs). In principle, BRMs are biologically active agents including antibodies, small peptides, and/or other (small) molecules that can influence the immune response. BRMs are already being used in the clinic to treat malignancies and autoimmune diseases. Repurposing such agents would allow for accelerated use against severe and potentially fatal IAV infections. In this review, we will address the potential therapeutic use of different BRM classes to modulate the immune response induced after IAV infections.
Obesity-Related Genetic Variants and Hyperuricemia Risk in Chinese Men

Objective: Obesity/metabolic syndrome and hyperuricemia are clinically associated; however, the association of obesity/metabolic syndrome-related genetic variants with hyperuricemia is not clear. Therefore, we assessed this association in Chinese men diagnosed with hyperuricemia in comparison to a non-hyperuricemia group. Methods: We genotyped 47 single nucleotide polymorphisms (SNPs) previously identified to be associated with obesity or metabolic syndrome in 474 adult males (aged ≥ 18 years) using multiplex polymerase chain reaction. Multivariate logistic regression was used to investigate the association between the genetic variations and hyperuricemia. Stratified analyses were applied to further assess the associations. Results: The obesity-related SNP in MSRA rs545854 significantly affected serum uric acid levels. In addition, the G-allele of rs545854 was positively associated with the risk of hyperuricemia [odds ratio (OR) = 2.80, 95% confidence interval (CI) = 1.19–6.64, P = 0.0188]. After adjusting the model for body mass index and central obesity, rs545854 was shown to be an independent factor increasing the risk of hyperuricemia (OR = 2.81, 95%CI = 1.18–6.70, P = 0.0196). Stratified analyses also showed a significant association between rs545854 and hyperuricemia among meat eaters (OR = 2.62, 95%CI = 1.09–6.26, P = 0.0308). Conclusion: The obesity-related SNP rs545854 was correlated with the serum uric acid level and risk of hyperuricemia in a male Chinese population. Therefore, men carrying this SNP could benefit from limiting their meat consumption to prevent hyperuricemia. These findings suggest an underlying genetic link between obesity and hyperuricemia worthy of further exploration.
Chemical Profiling and Biological Screening of Some River Nile Derived-Microorganisms

Aims Chemical and biological studies of the River Nile derived-microorganisms are limited. Hence, this work was carried out to screen the River Nile habitat. Identification of the isolated organisms, chemical profiling of their ethyl acetate extracts as well as screening of their antimicrobial, antileishmanial, antitrypanosomal, and antimalarial activities were investigated. Methods Identification of the microbial isolates were carried out using bacterial 16S rRNA and fungal 18S rRNA gene sequencing. Chemical profiling of the EtOAc extracts using LC-HRESIMS spectroscopy was carried out. The in vitro antimicrobial screening using the modified version of the CLSI method, antileishmanial and antitrypanosomal activities were screened using Leishmania donovani promastigote assay, L. donovani axenic amastigote assay, Trypanosoma brucei trypamastigotes assay and THP1 toxicity assay. The in vitro antimalarial activities against D6 (chloroquine sensitive) and W2 (chloroquine-resistant) strains of Plasmodium falciparum were evaluated. Results Seven isolated microorganisms were identified as Streptomyces indiaensis, Bacillus safensis, B. anthracis, Bacillus sp. , and Aspergillus awamori. Chemical investigation of different extracts showed several bioactive compounds, identified as; nigragillin, 5-caboxybenzofuran and dyramide B from A. awamori and actinopolysporin B from S. indiaensis. On the other hand many nitrogenous compounds with high molecular weights showed no hits that may correspond to new long chain and/or cyclic peptides. The EtOAc extract of B. safensis fermentation broth showed the highest activity against P. falciparum D6 and P. falciparum W2 (IC50 = 25.94 and 27.28 μg/mL, respectively), while two isolates S. indiaensis and Bacillus sp. RN-011 extracts showed the highest antitrypanosomal activity (IC50 = 0.8 and 0.96 μg/mL). Conclusion The River Nile could be a new source for production of promising bioactive leading compound where antimicrobial and antiparasitic activities may be correlated.
Genome-Wide Identification and Characterization of the PERK Gene Family in Gossypium hirsutum Reveals Gene Duplication and Functional Divergence

Proline-rich extensin-like receptor kinases (PERKs) are an important class of receptor kinases in plants. Receptor kinases comprise large gene families in many plant species, including the 15 PERK genes in Arabidopsis. At present, there is no comprehensive published study of PERK genes in G. hirsutum. Our study identified 33 PERK genes in G. hirsutum. Phylogenetic analysis of conserved PERK protein sequences from 15 plant species grouped them into four well defined clades. The GhPERK gene family is an evolutionarily advanced gene family that lost its introns over time. Several cis-elements were identified in the promoter regions of the GhPERK genes that are important in regulating growth, development, light responses and the response to several stresses. In addition, we found evidence for gene loss or addition through segmental or whole genome duplication in cotton. Gene duplication and synteny analysis identified 149 orthologous/paralogous gene pairs. Ka/Ks values show that most GhPERK genes experienced strong purifying selection during the rapid evolution of the gene family. GhPERK genes showed high expression levels in leaves and during ovule development. Furthermore, the expression of GhPERK genes can be regulated by abiotic stresses and phytohormone treatments. Additionally, PERK genes could be involved in several molecular, biological and physiological processes that might be the result of functional divergence.
Fermentation Biotechnology Applied to Cereal Industry By-Products: Nutritional and Functional Insights

Cereals are one of the major food sources in human diet and a large quantity of by-products is generated throughout their processing chain. These by-products mostly consist of the germ and outer layers (bran), deriving from dry and wet milling of grains, brewers' spent grain originating from brewing industry, or others originating during bread-making and starch production. Cereal industry by-products are rich in nutrients, but still they end up as feed, fuel, substrates for biorefinery, or waste. The above uses, however, only provide a partial recycle. Although cereal processing industry side streams can potentially provide essential compounds for the diet, their use in food production is limited by their challenging technological properties. For this reason, the development of innovative biotechnologies is essential to upgrade these by-products, potentially leading to the design of novel and commercially competitive functional foods. Fermentation has been proven as a very feasible option to enhance the technological, sensory, and especially nutritional and functional features of the cereal industry by-products. Through the increase of minerals, phenolics and vitamins bioavailability, proteins digestibility, and the degradation of antinutritional compounds as phytic acid, fermentation can lead to improved nutritional quality of the matrix. In some cases, more compelling benefits have been discovered, such as the synthesis of bioactive compounds acting as antimicrobial, antitumoral, antioxidant agents. When used for baked-goods manufacturing, fermented cereal by-products have enhanced their nutritional profile. The key factor of a successful use of cereal by-products in food applications is the use of a proper bioprocessing technology, including fermentation with selected starters. In the journey toward a more efficient food chain, biotechnological approaches for the valorization of agricultural side streams can be considered a very valuable help.
A New Surgical Site Infection Risk Score: Infection Risk Index in Cardiac Surgery

Various scoring systems attempt to predict the risk of surgical site infection (SSI) after cardiac surgery, but their discrimination is limited. Our aim was to analyze all SSI risk factors in both coronary artery bypass graft (CABG) and valve replacement patients in order to create a new SSI risk score for such individuals. A priori prospective collected data on patients that underwent cardiac surgery (n = 2020) were analyzed following recommendations from the Reporting of studies Conducted using Observational Routinely collected health Data (RECORD) group. Study participants were divided into two periods: the training sample for defining the new tool (2010–2014, n = 1298), and the test sample for its validation (2015–2017, n = 722). In logistic regression, two preoperative variables were significantly associated with SSI (odds ratio (OR) and 95% confidence interval (CI)): diabetes, 3.3/2–5.7; and obesity, 4.5/2.2–9.3. The new score was constructed using a summation system for punctuation using integer numbers, that is, by assigning one point to the presence of either diabetes or obesity. The tool performed better in terms of assessing SSI risk in the test sample (area under the Receiver-Operating Characteristic curve (aROC) and 95% CI, 0.67/055–0.76) compared to the National Nosocomial Infections Surveillance (NNIS) risk index (0.61/0.50–0.71) and the Australian Clinical Risk Index (ACRI) (0.61/0.50–0.72). A new two-variable score to preoperative SSI risk stratification of cardiac surgery patients, named Infection Risk Index in Cardiac surgery (IRIC), which outperforms other classical scores, is now available to surgeons. Personalization of treatment for cardiac surgery patients is needed.
The Cord Blood Insulin and Mitochondrial DNA Content Related Methylome

Mitochondrial dysfunction seems to play a key role in the etiology of insulin resistance. At birth, a link has already been established between mitochondrial DNA (mtDNA) content and insulin levels in cord blood. In this study, we explore shared epigenetic mechanisms of the association between mtDNA content and insulin levels, supporting the developmental origins of this link. First, the association between cord blood insulin and mtDNA content in 882 newborns of the ENVIRONAGE birth cohort was assessed. Cord blood mtDNA content was established via qPCR, while cord blood levels of insulin were determined using electrochemiluminescence immunoassays. Then the cord blood DNA methylome and transcriptome were determined in 179 newborns, using the human 450K methylation Illumina and Agilent Whole Human Genome 8 × 60 K microarrays, respectively. Subsequently, we performed an epigenome-wide association study (EWAS) adjusted for different maternal and neonatal variables. Afterward, we focused on the 20 strongest associations based on p-values to assign transcriptomic correlates and allocate corresponding pathways employing the R packages ReactomePA and RDAVIDWebService. On the regional level, we examined differential methylation using the DMRcate and Bumphunter packages in R. Cord blood mtDNA content and insulin were significantly correlated (r = 0.074, p = 0.028), still showing a trend after additional adjustment for maternal and neonatal variables (p = 0.062). We found an overlap of 33 pathways which were in common between the association with cord blood mtDNA content and insulin levels, including pathways of neurodevelopment, histone modification, cytochromes P450 (CYP)-metabolism, and biological aging. We further identified a DMR annotated to Repulsive Guidance Molecule BMP Co-Receptor A (RGMA) linked to cord blood insulin as well as mtDNA content. Metabolic variation in early life represented by neonatal insulin levels and mtDNA content might reflect or accommodate alterations in neurodevelopment, histone modification, CYP-metabolism, and aging, indicating etiological origins in epigenetic programming. Variation in metabolic hormones at birth, reflected by molecular changes, might via these alterations predispose children to metabolic diseases later in life. The results of this study may provide important markers for following targeted studies.
A CNN-Based Method for Intent Recognition Using Inertial Measurement Units and Intelligent Lower Limb Prosthesis

Powered intelligent lower limb prosthesis can actuate the knee and ankle joints, allowing transfemoral amputees to perform seamless transitions between locomotion states with the help of an intent recognition system. However, prior intent recognition studies often installed multiple sensors on the prosthesis, and they employed machine learning techniques to analyze time-series data with empirical features. We alternatively propose a novel method for training an intent recognition system that provides natural transitions between level walk, stair ascent / descent, and ramp ascent / descent. Since the transition between two neighboring states is driven by motion intent, we aim to explore the mapping between the motion state of a healthy leg and an amputee’s motion intent before the upcoming transition of the prosthesis. We use inertial measurement units (IMUs) and put them on the healthy leg of lower limb amputees for monitoring its locomotion state. We analyze IMU data within the early swing phase of the healthy leg, and feed data into a convolutional neural network (CNN) to learn the feature mapping without expert participation. The proposed method can predict the motion intent of both unilateral amputees and the able-bodied, and help to adaptively calibrate the control strategy for actuating powered intelligent prosthesis in advance. The experimental results show that the recognition accuracy can reach a high level (94.15% for the able-bodied, 89.23% for amputees) on 13 classes of motion intent, containing five steady states on different terrains as well as eight transitional states among the steady states.
Relationship between toxoplasmosis and obsessive compulsive disorder: A systematic review and meta-analysis

Background A few studies investigated the relationship between toxoplasmosis and mental disorders, such as obsessive compulsive disorder (OCD). However, the specific nature of the association between Toxoplasma gondii (T. gondii) infection and OCD is not yet clear. The aim of this study was to collect information on the relationship between OCD and toxoplasmosis and assess whether patients with toxoplasmosis are prone to OCD. Methods For the purpose of this study, 6 major electronic databases and the Internet search engine Google Scholar were searched for the published articles up to July 30th, 2018 with no restriction of language. The inverse variance method and the random effect model were used to combine the data. The values of odds ratio (OR) were estimated at 95% confidence interval (CI). Results A total of 9 case-control and 3 cross-sectional studies were included in our systematic review. However, 11 of these 12 articles were entered into the meta-analysis containing 9873 participants, out of whom 389 were with OCD (25.96% positive for toxoplasmosis) and 9484 were without OCD (17.12% positive for toxoplasmosis). The estimation of the random effect model indicated a significant common OR of 1.96 [95% CI: 1.32–2.90]. Conclusion This systematic review and meta-analysis revealed that toxoplasmosis could be as an associated factor for OCD (OR = 1.96). However, further prospective investigations are highly recommended to illuminate the underlying pathophysiological mechanisms of T. gondii infection in OCD and to better investigate the relationship between OCD and T. gondii infection.
Management of Iron Deficiency Anaemia in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a group of chronic relapsing inflammatory disorders affecting the large and small intestine, with a rising worldwide incidence and prevalence. Anaemia is the most common extraintestinal manifestation of IBD, correlating with disease activity, and tending to relapse even after successful therapy. Iron deficiency is the most common cause; however, it often manifests in combination with anaemia of inflammation. As such, multiple parameters are used for the diagnosis of iron deficiency anaemia in IBD. Timely recognition and selection of appropriate therapy leads to an improvement in the quality of life and prevention of potential sequelae. Oral iron can be effective under specific circumstances; however, as luminal iron changes microbiota and bacterial metabolism, oral administration should be avoided. Intravenous iron is preferred as it bypasses the sites of inflammation. Nevertheless, the optimization of IBD treatment should occur simultaneously, as this improves both patient condition and response to iron therapy. Herein, we discuss the screening, diagnosis, selection of therapy, and follow-up for iron deficiency anaemia in IBD.
Cytokinin inhibits cotton fiber initiation by disrupting PIN3a-mediated asymmetric accumulation of auxin in the ovule epidermis

Abstract Auxin-dependent cell expansion is crucial for initiation of fiber cells in cotton (Gossypium hirsutum), which ultimately determines fiber yield and quality. However, the regulation of this process is far from being well understood. In this study, we demonstrate an antagonistic effect between cytokinin (CK) and auxin on cotton fiber initiation. In vitro and in planta experiments indicate that enhanced CK levels can reduce auxin accumulation in the ovule integument, which may account for the defects in the fiberless mutant xu142fl. In turn, supplementation with auxin can recover fiber growth of CK-treated ovules and mutant ovules. We further found that GhPIN3a is a key auxin transporter for fiber-cell initiation and is polarly localized to the plasma membranes of non-fiber cells, but not to those of fiber cells. This polar localization allows auxin to be transported within the ovule integument while specifically accumulating in fiber cells. We show that CKs antagonize the promotive effect of auxin on fiber cell initiation by undermining asymmetric accumulation of auxin in the ovule epidermis through down-regulation of GhPIN3a and disturbance of the polar localization of the protein.