Miracle-dz/UniFAR-FTUs huggingface dataset:
The dynamic behavior of storage organelles in developing cereal seeds and its impact on the production of recombinant proteins

Cereal endosperm is a highly differentiated tissue containing specialized organelles for the accumulation of storage proteins, which are ultimately deposited either within protein bodies derived from the endoplasmic reticulum, or in protein storage vacuoles (PSVs). During seed maturation endosperm cells undergo a rapid sequence of developmental changes, including extensive reorganization and rearrangement of the endomembrane system and protein transport via several developmentally regulated trafficking routes. Storage organelles have been characterized in great detail by the histochemical analysis of fixed immature tissue samples. More recently, in vivo imaging and the use of tonoplast markers and fluorescent organelle tracers have provided further insight into the dynamic morphology of PSVs in different cell layers of the developing endosperm. This is relevant for biotechnological applications in the area of molecular farming because seed storage organelles in different cereal crops offer alternative subcellular destinations for the deposition of recombinant proteins that can reduce proteolytic degradation, allow control over glycan structures and increase the efficacy of oral delivery. We discuss how the specialized architecture and developmental changes of the endomembrane system in endosperm cells may influence the subcellular fate and post-translational modification of recombinant glycoproteins in different cereal species.
Side effects associated with psychotropic medications in patients with bipolar disorder: evidence from two independent samples

Available evidence concerning the side effects experienced by bipolar disorder (BD) patients under naturalistic conditions has been poorly investigated. The aim of this study was therefore to investigate side effects related to major psychotropic drugs in two independent samples of BD patients naturalistically treated with mood stabilizers, antidepressants, antipsychotics and/or anxiolytics. Overall, 3654 patients from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample and 282 patients from the Clinical Outcome and Psycho-Education for Bipolar Disorder (COPE-BD) sample were included. The primary outcome measure was the influence of each class of psychotropic drugs under investigation on the emergence of any side effect, as measured with the monitoring form in the STEP-BD study and the Udvalg for Kliniske Undersøgelser Side Effect Rating Scale in the COPE-BD study. Secondary outcome measures included the effects of such drugs on psychic, neurologic, autonomic and other side effects. Mood stabilizers and antipsychotics were associated with high rates of side effects in both samples. Furthermore, antipsychotics were specifically associated with psychic side effects, whereas mood stabilizers were specifically associated with neurologic side effects. Our results largely confirm in a naturalistic setting results previously observed in randomized controlled trials focusing on BD patients.
Interferon and alternative activation of monocyte/macrophages in systemic sclerosis-associated pulmonary arterial hypertension.

OBJECTIVE To explore the relationship between biomarkers of pulmonary arterial hypertension (PAH), interferon (IFN)-regulated gene expression, and the alternative activation pathway in systemic sclerosis (SSc). METHODS Peripheral blood mononuclear cells (PBMCs) were purified from healthy controls, patients with idiopathic PAH, and SSc patients (classified as having diffuse cutaneous SSc, limited cutaneous SSc [lcSSc] without PAH, and lcSSc with PAH). IFN-regulated and "PAH biomarker" genes were compared after supervised hierarchical clustering. Messenger RNA levels of selected IFN-regulated genes (Siglec1 and MX1), biomarker genes (IL13RA1, CCR1, and JAK2), and the alternative activation marker gene (MRC1) were analyzed on PBMCs and on CD14- and CD14+ cell populations. Interleukin-13 (IL-13) and IL-4 concentrations were measured in plasma by immunoassay. CD14, MRC1, and IL13RA1 surface expression was analyzed by flow cytometry. RESULTS Increased PBMC expression of both IFN-regulated and biomarker genes distinguished SSc patients from healthy controls. Expression of genes in the biomarker cluster, but not in the IFN-regulated cluster, distinguished lcSSc with PAH from lcSSc without PAH. The genes CCR1 (P<0.001) and JAK2 (P<0.001) were expressed more highly in lcSSc patients with PAH compared with controls and mainly by CD14+ cells. MRC1 expression was increased exclusively in lcSSc patients with PAH (P<0.001) and correlated strongly with pulmonary artery pressure (r=0.52, P=0.03) and higher mortality (P=0.02). MRC1 expression was higher in CD14+ cells and was greatly increased by stimulation with IL-13. IL-13 concentrations in plasma were most highly increased in lcSSc patients with PAH (P<0.001). CONCLUSION IFN-regulated and biomarker genes represent distinct, although related, clusters in lcSSc patients with PAH. MRC1, a marker for the effect of IL-13 on alternative monocyte/macrophage activation, is associated with this severe complication and is related to mortality.
Insulin receptor gene mutations in iranian patients with type II diabetes mellitus.

BACKGROUND Patients with diabetes mellitus type II suffer from hyperglycemia because they are not able to use the insulin that they produce, often due to inadequate function of insulin receptors. There are some evidences that this deficiency is inherited in a dominant autosomal manner and leads to the malfunction of the pancreatic beta cells resulting in insulin excretion disorders. In this study, we sought to identify mutations in the insulin receptor (INSR) gene, which can cause insulin resistance in type II diabetic patients. METHODS DNA was extracted from peripheral blood cells of the patients (n = 128) diagnosed with type II diabetes. All 22 exons of the INSR gene of the patients were analyzed for mutations running PCR, conformation-sensitive gel electrophoresis and DNA sequencing, consecutively. RESULTS Approximately 26% of the patients had genetic mutations; however, most of them were not reported. These mutations include exon 2 (His171Asn, Ile172Ser, Cys196Ser and Ser210Arg), exon 3 (Gly227Asp and Gly232Ser), exon 8 (Thr543Ser), exon 9 (a heterozygote was observed with no change in phenylalanine at position 669), exon 13 (two heterozygotes: Arg890Pro with Asn865 remaining unchanged), exon 14 (Ala906Gly and Pro918Trp with Arg902 unchanged), exon 17 (Val1086Glu) and exon 19 (His1157Gln with Thr1172 unchanged). CONCLUSION The lack of similar mutation records in literature and genetic data banks may suggest a geographic pattern for these INSR gene variants in our population.
Orthology, Function and Evolution of Accessory Gland Proteins in the Drosophila repleta Group

The accessory gland proteins (Acps) of Drosophila have become a model for the study of reproductive protein evolution. A major step in the study of Acps is to identify biological causes and consequences of the observed patterns of molecular evolution by comparing species groups with different biology. Here we characterize the Acp complement of Drosophila mayaguana, a repleta group representative. Species of this group show important differences in ecology and reproduction as compared to other Drosophila. Our results show that the extremely high rates of Acp evolution previously found are likely to be ubiquitous among species of the repleta group. These evolutionary rates are considerably higher than the ones observed in other Drosophila groups' Acps. This disparity, however, is not accompanied by major differences in the estimated number of Acps or in the functional categories represented as previously suggested. Among the genes expressed in accessory glands of D. mayaguana almost half are likely products of recent duplications. This allowed us to test predictions of the neofunctionalization model for gene duplication and paralog evolution in a more or less constrained timescale. We found that positive selection is a strong force in the early divergence of these gene pairs.
Conversion therapy of gastric cancer with massive malignant ascites and ovarian metastases by systemic and intraperitoneal chemotherapy

Intravenous and intraperitoneal paclitaxel with S-1 is showing promising results in gastric cancer with peritoneal metastases. We herein report a successful conversion of unresectable to resectable disease using combination chemotherapy with trastuzumab. The patient was a 39-year-old woman with human epidermal growth factor receptor 2-positive gastric cancer with peritoneal, pulmonary and bilateral ovarian metastases. After 6 cycles of S-1 plus cisplatin with trastuzumab, followed by 15 cycles of intravenous and intraperitoneal paclitaxel with S-1 and trastuzumab, the pulmonary and peritoneal metastases exhibited complete response and no evidence of malignancy was found on diagnostic laparoscopy. We performed metastasectomy of the bilateral sizeable ovaries, followed by total gastrectomy. The patient had no recurrence for 16 months after the gastrectomy. Therefore, satisfactory response to systemic and intraperitoneal chemotherapy may convert unresectable to resectable disease, and primary tumor resection with ovarian metastasectomy may prolong survival. This combination chemotherapy has the potential of becoming a conversion therapy for gastric cancer with peritoneal metastases, even if ascites and ovarian metastases are extensive.
Romantic love: a mammalian brain system for mate choice

Mammals and birds regularly express mate preferences and make mate choices. Data on mate choice among mammals suggest that this behavioural ‘attraction system’ is associated with dopaminergic reward pathways in the brain. It has been proposed that intense romantic love, a human cross-cultural universal, is a developed form of this attraction system. To begin to determine the neural mechanisms associated with romantic attraction in humans, we used functional magnetic resonance imaging (fMRI) to study 17 people who were intensely ‘in love’. Activation specific to the beloved occurred in the brainstem right ventral tegmental area and right postero-dorsal body of the caudate nucleus. These and other results suggest that dopaminergic reward and motivation pathways contribute to aspects of romantic love. We also used fMRI to study 15 men and women who had just been rejected in love. Preliminary analysis showed activity specific to the beloved in related regions of the reward system associated with monetary gambling for uncertain large gains and losses, and in regions of the lateral orbitofrontal cortex associated with theory of mind, obsessive/compulsive behaviours and controlling anger. These data contribute to our view that romantic love is one of the three primary brain systems that evolved in avian and mammalian species to direct reproduction. The sex drive evolved to motivate individuals to seek a range of mating partners; attraction evolved to motivate individuals to prefer and pursue specific partners; and attachment evolved to motivate individuals to remain together long enough to complete species-specific parenting duties. These three behavioural repertoires appear to be based on brain systems that are largely distinct yet interrelated, and they interact in specific ways to orchestrate reproduction, using both hormones and monoamines. Romantic attraction in humans and its antecedent in other mammalian species play a primary role: this neural mechanism motivates individuals to focus their courtship energy on specific others, thereby conserving valuable time and metabolic energy, and facilitating mate choice.
Shortcomings of the laboratory‐derived median lethal concentration for predicting mortality in field populations: Exposure duration and latent mortality

Exposure duration and intensity (concentration or dose) determine lethal effects of toxicants. However, environmental regulators have focused on exposure intensity and have considered duration only peripherally. Conventional testing for toxicology tends to fix exposure time and to use the median lethal concentration (LC50) at that time to quantify mortality. Fixing the exposure duration and selecting the 50% mortality level for reasons of statistical and logistical convenience result in the loss of ecologically relevant information generated at all other times and ignore latent mortality that manifests after the exposure ends. In the present study, we used survival analysis, which is widely employed in other fields, to include both time and concentration as covariates and to quantify latent mortality. This was done with two contrasting toxicants, copper sulfate (CuSO4) and sodium pentachlorophenol (NaPCP). Amphipods (Hyalella azteca) were exposed to different toxicant concentrations, and the percentage mortalities were noted both during and after the exposure ended. For CuSO4 at the conventional 48‐h LC50 concentrations, the predicted proportions dead after including latent mortality were 65 to 85%, not 50%. In contrast, only 5% or fewer additional animals died if the latent mortality was included for NaPCP. The data (including exposure time, concentration, and proportion dead at each time) for each toxicant were then successfully fit with survival models. The proportion of organisms dying at any combination of exposure concentration and time can be predicted from such models. Survival models including latent mortality produced predictions of lethal effects that were more meaningful in an ecological or field context than those from conventional LC50 methods.
Evidence for Positive Effects of Date Extract That Attenuates Thermal Hyperalgesia in a Diabetic Rat Model of Neuropathic Pain

Aim: Diabetic neuropathic pain is one of the pains which hardly respond to pharmaceutical treat. Today, various chemical and herbal compounds have been used to reduce pain. The aim of this study is to compare the effect of date extract and melatonin in preventing pain in diabetic rats.Method: To study hyperalgesia response and to compare the effect of date extract and melatonin in preventing pain, hot plate and tail flick tests were used. After prescribing single dose of streptozotocin to rats and approving their diabetes, treatment rats received date extract (4ml/kg/day) or melatonin [10 mg/kg/day, intraperitoneally (i.p.)] for a period of 6 weeks. At the end of the sixth week, control and treated rats were examined by thermal pain response and explorative activity tests.Results: According to hot plate results, response time to thermal pain in treated group showed a significant decrease in comparison with the control group (P 0.01). Prescription of date extract increased response time to thermal pain in comparison with treated group (P 0.01), so that response time approximated to control group. Although melatonin approximated to the response time to control group, the significant difference was not observed among melatonin receivers and other groups. In the assessment of diabetic neuropathy on the explorative activity of rats in an open field behavioral test, total distance moved and rearing frequency were significantly decreased, while administration of date extract did also improve motor deficits induced by STZ. Conclusions:Findings of this study showed that date extract decreased thermal hyperalgesia and can prevent pain resulted from diabetic neuropathy.
Evaluation of Patients’ Response Toward Osteoporosis Letter Intervention Versus Phone Call Plus Letter Intervention

Introduction: The aim of this study was to compare the effectiveness of 2 interventions in prompting patients to obtain osteoporosis follow-up after a fracture. Our hypothesis was that a phone call plus letter would yield greater response toward osteoporosis evaluation versus a letter alone to patients after sustaining a fragility fracture. Materials and Methods: Prospective study randomized 141 patients age 50 years and older with a fragility fracture into 3 groups for comparison. Group 1 (letter only) patients received a letter 3 months after their diagnosis of fracture indicating their risk for osteoporosis and urging them to follow-up for evaluation. Group 2 (phone call plus letter) patients were contacted via phone 3 months after their diagnosis of fracture. A letter followed the phone call. Group 3 (control) patients were neither contacted via phone nor sent a letter. All groups were contacted via phone 6 months after their initial visit to determine if they followed up for evaluation. Results: In group 1, 23 (52.27%) of 44 had follow-up, and 21 (47.73%) of 44 did not follow-up. In group 2, 30 (62.5%) of 48 had follow-up, and 18 (37.50%) of 48 did not follow-up. In group 3, 6 (12.24%) of 49 had some sort of follow-up, and 43 (87.76%) of 49 did not have any follow-up. A statistical significance was achieved between group 3 (control) and both groups 1 and 2 with regard to follow-up (P < .0001). The results did not show a statistically significant difference between Groups 1 and 2, however, there was a trend toward improved response with a phone call plus letter (P = .321). Conclusion: A more personalized approach with a phone call plus follow-up letter to patients increased osteoporosis follow-up care by an additional 10%, however, this was not a statistically significant difference from just sending out a letter alone.
Limited predictability of postmortem human brain tissue quality by RNA integrity numbers

The RNA integrity number (RIN) is often considered to be a critical measure of the quality of postmortem human brains. However, it has been suggested that RINs do not necessarily reflect the availability of intact mRNA. Using the Agilent bioanalyzer and qRT‐PCR, we explored whether RINs provide a meaningful way of assessing mRNA degradation and integrity in human brain samples by evaluating the expression of 3′–5′ mRNA sequences of the cytochrome C‐1 (CYC1) gene. Analysis of electropherograms showed that RINs were not consistently correlated with RNA or cDNA profiles and appeared to be poor predictors of overall cDNA quality. Cycle thresholds from qRT‐PCR analysis to quantify the amount of CYC1 mRNA revealed positive correlations of RINs with amplification of full‐length transcripts, despite the variable degree of linear degradation along the 3′–5′ sequence. These data demonstrate that in postmortem human brain tissue the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality.
Model Formulation: A Risk Analysis Method to Evaluate the Impact of a Computerized Provider Order Entry System on Patient Safety

OBJECTIVES Quantitative evaluation of safety after the implementation of a computerized provider order entry (CPOE) system, stratification of residual risks to drive future developments. DESIGN Comparative risk analysis of the drug prescription process before and after the implementation of CPOE system, according to the Failure Modes, Effects and Criticality Analysis (FMECA) method. MEASUREMENTS The failure modes were defined and their criticality indices calculated on the basis of the likelihood of occurrence, potential severity for patients, and detection probability. Criticality indices of handwritten and electronic prescriptions were compared, the acceptability of residual risks was discussed. Further developments were proposed and their potential impact on the safety was estimated. RESULTS The sum of criticality indices of 27 identified failure modes was 3813 for the handwritten prescription, 2930 (-23%) for CPOE system, and 1658 (-57%) with 14 enhancements. The major safety improvements were observed for errors due to ambiguous, incomplete or illegible orders (-245 points), wrong dose determination (-217) and interactions (-196). Implementation of targeted pop-ups to remind treatment adaptation (-189), vital signs (-140), and automatic edition of documents needed for the dispensation (-126) were the most promising proposed improvements. CONCLUSION The impact of a CPOE system on patient safety strongly depends on the implemented functions and their ergonomics. The use of risk analysis helps to quantitatively evaluate the relationship between a system and patient safety and to build a strategy for continuous quality improvement, by selecting the most appropriate improvements to the system.
Water reduction in waste-activated sludge by resettling and filtration in batch. Phase (1): pilot-scale experiments to optimize performance

This article describes an effective procedure for reducing the water content of excess sludge production from a wastewater treatment plant by increasing its concentration and, as a consequence, minimizing the volume of sludge to be managed. It consists of a pre-dewatering sludge process, which is used as a preliminary step or alternative to the thickening. It is made up of two discontinuous sequential stages: the first is resettling and the second, filtration through a porous medium. The process is strictly physical, without any chemical additives or electromechanical equipment intervening. The experiment was carried out in a pilot-scale system, consisting of a column of sedimentation that incorporates a filter medium. Different sludge heights were tested over the filter to verify the influence of hydrostatic pressure on the various final concentrations of each stage. The results show that the initial sludge concentration may increase by more than 570% by the end of the process with the final volume of sludge being reduced in similar proportions and hydrostatic pressure having a limited effect on this final concentration. Moreover, the value of the hydrostatic pressure at which critical specific cake resistance is reached is established.
Lagged Effect of Diurnal Temperature Range on Mortality in a Subtropical Megacity of China

Background Many studies have found extreme temperature can increase the risk of mortality. However, it is not clear whether extreme diurnal temperature range (DTR) is associated with daily disease-specific mortality, and how season might modify any association. Objectives To better understand the acute effect of DTR on mortality and identify whether season is a modifier of the DTR effect. Methods The distributed lag nonlinear model (DLNM) was applied to assess the non-linear and delayed effects of DTR on deaths (non-accidental mortality (NAD), cardiovascular disease (CVD), respiratory disease (RD) and cerebrovascular disease (CBD)) in the full year, the cold season and the warm season. Results A non-linear relationship was consistently found between extreme DTR and mortality. Immediate effects of extreme low DTR on all types of mortality were stronger than those of extreme high DTR in the full year. The cumulative effects of extreme DTRs increased with the increment of lag days for all types of mortality in cold season, and they were greater for extreme high DTRs than those of extreme low DTRs. In hot season, the cumulative effects for extreme low DTRs increased with the increment of lag days, but for extreme high DTR they reached maxima at a lag of 13 days for all types of mortality except for CBD(at lag6 days), and then decreased. Conclusions Our findings suggest that extreme DTR is an independent risk factor of daily mortality, and season is a modifier of the association of DTR with daily mortality.