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Bioinspired polyimide film with fire retardant and gas barrier properties by gravity-...
Qiao-Xi Yu
Run-Xin Bei

Qiao-Xi Yu

and 7 more

May 26, 2023
Flame retardants play a crucial role in improving the flame retardant properties of polymer materials. In recent years, environmental problems caused by flame retardants have attracted widespread attention. It is urgent to use green and effective methods to prepare flame retardant polymers. Bioinspired nanocomposites with layered structures seem to provide an effective idea, but in general, the hydrophilic properties of their raw materials limit their applications in certain fields. Here, we prepared biomimetic composites with a layered “brick-and-mortar” structure by gravity-induced deposition using polyimide as the polymer matrix and montmorillonite (MMT) as the filler. The well-arranged structures of the composite material could isolate oxygen and prevent combustible gases from escaping. The gas barrier performance has been greatly improved, in which the water vapor transmission rate (WVTR) and the oxygen transmission rate (OTR) decreased by 99.18% and three orders of magnitude, respectively. The flame retardant performance has also been improved, and its limiting oxygen index can reach 67.9%. More importantly, the polyimide matrix can be converted to water-insoluble by thermal imidization of water-soluble poly (amic acid) salt precursors, which endows the composites with low hygroscopicity. Such coating containing MMT can protect against polyurethane (PU) foam from fire. During the conical calorimetric test, the coated sample self-extinguished, and the peak heat release rate, total heat release, total smoke production is significantly decreased by 53.39%, 40.69%, and 53.03%, respectively. Taking advantage of these properties, this work utilizes a facile method to prepare biomimetic composites with low moisture absorption, excellent gas barrier properties, and flame retardancy, which have great application potential.
Efficacy and Mechanism of Combining Radiotherapy and Immunotherapy in Stage IV NSCLC
Mingyue Wang
* Jing-Sui

Mingyue Wang

and 6 more

May 26, 2023
Lung cancer is the leading cause of cancer-related deaths worldwide. About 85% of lung cancer patients have NSCLC; most are diagnosed with stage IV disease at initial presentation. With the continuous development of oncology, immunotherapy or immune chemotherapy has become the first-line treatment for patients with stage IV NSCLC. However, a proportion of patients still develop resistance to the treatment regimen and experience local progression, and primary lung lesion progression is the main progression pattern of stage IV NSCLC. Preclinical and clinical studies have demonstrated that radiotherapy can induce a systemic anti-tumor immune response and that adding local radiotherapy before cancer progression can prolong survival. Therefore, we considered whether adding local radiotherapy before the progression of a pulmonary lesion in stage IV NSCLC patients receiving immunotherapy or immune chemotherapy would be beneficial. The present review focused on the anti-tumor efficacy of radiotherapy and immunotherapy, emphasizing the time of addition of radiotherapy and the safety of combination therapy for stage IV NSCLC and understanding the underlying mechanism.
Information processing speed, visuospatial working memory and cognitive failures in c...
Fateme Moradi
Ghasem Askarizadeh

Fateme Moradi

and 2 more

May 26, 2023
Previous studies have shown that aging can contribute to cognitive decline in patients with COPD, whereas cognitive reserve (CR) can be a protective factor against cognitive decline following brain pathology. However, the effects of CR and the interaction between age and CR on cognitive functions in patients with COPD have not been studied. We investigated the effects of age as a risk factor and CR as a protective factor on information processing speed, visuospatial working memory, and cognitive failures in 104 middle-aged (Mage = 58.75 years, SDage = 3.51) and 104 elderly (Mage = 69.43 years, SDage = 3.12) patients with COPD. In addition, this study aimed to explore the interaction effect of age and CR on information processing speed, visuospatial working memory, and cognitive failures in middle-aged and elderly patients with COPD. The findings of the present study showed that (1) age significantly affects information processing speed, visuospatial working memory, and cognitive failures in patients with COPD. (2) CR has a significant effect on information processing speed and cognitive failures in COPD patients, but we did not observe the effect of CR on visuospatial working memory in COPD patients. It was also found that (3) the interaction effect of age and CR was only observed on cognitive failures, while the interaction of age and CR had no significant effect on information processing speed and visuospatial working memory in COPD patients. This study brings to light the differential effects of age and CR on the cognitive domains in COPD patients.
The Crucial Role of Hippocampus Cyclooxygenase-2 Plays in Synaptic Plasticity and Mem...
Hong Ni
Zhongzhao Guo

Hong Ni

and 6 more

November 02, 2022
It is generally accepted that Cyclooxygenase-2 (COX-2) is activated to cause inflammation. However, COX-2 is also constitutively expressed at the postsynaptic dendrites and excitatory terminals of the cortical and spinal cord neurons. Although some evidence suggests that COX-2 release during neuronal signaling may be pivotal for regulating the function of memory, the significance of constitutively expressed COX-2 in neuron is still unclear. This research aims to discover the role of COX-2 in memory beyond neuroinflammation and to determine whether the inhibition of COX-2 can cause cognitive dysfunction by influencing dendritic plasticity and its underlying mechanism. The cognitive ability was assessed by novel object recognition task (NORT) and Morris water maze (MWM) test. Immunofluorescence, Golgi-cox staining were used to observe dendritic synaptic. Gamma oscillation in hippocampus CA1 was performed by Tetrode in-vivo recording. Prostaglandins were measured by HPLC/mass spectrometry. We observed the expressions of cyclic adenosine monophosphate (cAMP)/ brain-derived neurotrophic factor (BDNF) pathway proteins in hippocampus and N2a cells by Elisa and western blot. We found COX-2 gene knockout (KO) could significantly impact the learning and memory ability; reduce the expression of postsynaptic density protein 95 (PSD95) in the neuron; cause synaptic disorder; influence gamma oscillation and reduce the expression prostaglandin (PG) E2, cAMP, phosphorylated protein kinase A (p-PKA), phosphorylated cAMP response element binding protein (p-CREB) and BDNF in the hippocampus. It suggested COX-2 might play a critical role in learning, regulating synaptic plasticity and gamma oscillation in the hippocampus CA1 by regulating COX-2/BDNF signaling pathway.
Relationship between episodes of fever and neutropenia and five-year survival rate fo...
R. Valenzuela
M. Santolaya

R. Valenzuela

and 4 more

May 26, 2023
Background: Cancer is one of the most significant non-transmissible diseases at public health level, and febrile neutropenia (FN) one of its most serious life threatening complications. Objective: To estimate 5-year survival rates for children with cancer and FN from a referral health center in Santiago, Chile, by clinical-demographic variables. Method: Prognostic and analytic historical cohort survival study. (FONDECYT nº 1090194, 2009-2011). Results: 116 subjects were included, and grouped in three categories, by type of cancer: 1) leukemia/lymphomas (51.7%), 2) osteosarcoma (25.9%) and 3) another type of solid organ tumors (22.4%), the median number of days between chemotherapy and the first episode of FN was 5 days [1-7], 7 [7-8] and 7 [5-8] respectively. The five year overall specific survival rate was 64.7%. There were protective factors identified through Cox Model: age, post cancer comorbidity and average educational level of the caregiver. Risk factors identified were: presence of another type of solid organ tumor (HR 3.43 95% CI 1.64-7.19), sepsis (HR 2.89 95% CI 1.47-5.70), delay in chemotherapy treatment (HR 2.94 95% CI 1.17-7.40) and invasive fungal infection (HR 3.36 95% CI 1.22-9.22). Conclusion: This is the first pediatric study in Chile to analyze prognostic factors in children with cancer and FN. The predictor variables that were identified comply with previous reports from international literature.
Scoping review of relationship between alcohol, memory consolidation, and ripple acti...
Marina Ruelas
Rita Fuentes-Aguilar (Second Corresponding Author)

Marina Ruelas

and 2 more

May 26, 2023
Alcohol abuse is not only responsible for 5.3% of the total deaths in the world, but also has a substantial impact on neurological and memory disabilities throughout the population. One extensively studied brain area involved in cognitive functions is the hippocampus. Evidence in several rodent models has shown that ethanol produces cognitive impairment in hippocampal-dependent tasks and that the damage is varied according to the stage of development at which the rodent was exposed to ethanol and the dose. To the authors’ knowledge, there is a biomarker for cognitive processes in the hippocampus that has not been evaluated in association with memory impairment by alcohol administration. This biomarker is called Sharp Wave Ripples which are synchronous neuronal population events that are well known to be involved in memory consolidation. Methodologies for facilitation or automatic identification of ripples and their analysis have been reported for a wider bandwidth than Sharp Wave Ripples. This review is focused on communicating the state-of-the art about the relationship between alcohol, memory consolidation and ripple activity as well as the use of the main methodologies to identify SWRs automatically.
First record of abortion of single co-twin in an Arabian mare and continuity of the o...
Mohamed Derbala
Mary Sargious

Mohamed Derbala

and 3 more

May 26, 2023
Twin pregnancies in Arabian horses is a major cause of abortion. In all cases when the abortion occurs, it occurs for both fetuses. Unusually in the case described here, which we believe has not previously been documented in Arabian horses, one fetus aborted in undersized and representing an age of 4 months. The other fetus completed the gestation and reached full term followed by birth. The authors postulated that one fetus underwent a stage of diapause like marsupials in a blastocyst stage then re-grew again, followed by abortion. The parentage analysis confirmed that both feti are derived from the same dam and sire stallion.
Research on familial defect attribution technology of measurement assets based on imp...
xiang Zhang
Men  Qi

xiang Zhang

and 2 more

May 26, 2023
A large amount of data has been accumulated in the technical supervision work of power grid enterprises for many years. Considering that the family defects of power equipment have a great influence on equipment condition assessment, this paper introduces an improved hierarchical clustering method based on the analysis of the traditional hierarchical clustering method to automatically identify and cluster the family status data of power equipment. The quantitative assessment of the family defect factor is then given. The family defect assessment is combined with the MMS communication network equipment in the substation communication network, which effectively and reasonably reflects the impact of various types of family defects on the health status of the equipment and provides a strong basis for maintenance decision making.
Laplace’s Law and Pascal’s Principle Dictate Birth Timing and Pregnancy Duration Thro...
Ali Hegazy

Ali Hegazy

May 26, 2023
Background Failure to understand uterine function during pregnancy is a major shortcoming of healthcare. Objective To support the hypothesis and we would call it, Hegazy’s Hypothesis for Gestation. Study Design: The thesis of this hypothesis is derived from a study that was carried out in Australia and published in PLOS in 2010. Sokolowski P et al. 2010. Human Uterine Wall Tension Trajectories and the Onset of Parturition. PLoS ONE 5(6): e11037. Results Pregnancy is a state of balance between the two opposing and interactive inhibitory and stimulatory systems secondary to EUWT mechano-transduction and Progesterone/estrogen stimulation. Pregnancy is mainly maintained through a stretch-dependent inhibitory system. Contractions of the stimulatory system transform the cervix into the lower uterine segment causing EUWT failure, which terminates the pregnancy. Light-dark cycle modulation of interactive inhibitory and stimulatory systems divides gestation into five clinical phases. Pregnancy interval and circadian timers are achieved by a single mechanism, namely EUWT failure, secondary to the complete loss of cervical strength nocturnally. Inhibitory system malfunction causes preterm labor, and most of the current therapeutic modalities for pre-term labor are focusing on delaying or preventing EUWT failure. Stimulatory system malfunction causes post-term pregnancy, and the combined malfunction of the two systems causes labor dystocia. Conclusion EUWT creation, autonomic maintenance, and autonomic EUWT termination make pregnancy an autonomic cycle with constant intervals and circadian timers. EUWT malfunctions alter birth timing and/or mode of delivery. Laplace’s law and Pascal’s principle measure EUWT which might be the laws of physics that genetically pregnancy duration.
Integrating ecological and evolutionary perspectives to predict the multi-generationa...
Debora Goedert
Henrik Jensen

Debora Goedert

and 2 more

May 26, 2023
Natural dispersal between populations, and resulting immigration, influences population size and genetic diversity and is therefore a key process driving reciprocal interactions between ecological and evolutionary dynamics. Both ecological and evolutionary consequences of dispersal fundamentally depend on the relative fitnesses of immigrants and their various descendants manifested in the context of natural environments. Yet, despite this commonality, recent research advances in predicting immigrants' legacies remain substantially disconnected across disciplines. To bridge resulting divides, we synthesize empirical and theoretical work examining fitness consequences of inter-breeding across the full spectrum of genetic divergence from inbred lines to inter-specific hybridization. We demonstrate how common underlying processes can generate positive or negative fitness consequences of immigration depending on interacting genetic and environmental effects. Impacts of inter-breeding following natural dispersal among sub-populations could consequently vary dramatically, shaping eco-evolutionary outcomes. Yet, our systematic literature review reveals a striking paucity of empirical studies that quantify multi-generational fitness consequences of immigration in natural metapopulations, precluding general inferences on outcomes. Hence, to provide new impetus, we highlight key theoretical and empirical gaps, and outline how cutting-edge statistical and genomic tools could be combined with multi-generational field datasets to advance understanding of dispersal-mediated drivers and constraints on eco-evolutionary dynamics.
De-novo genome assembly of the invasive mosquito species Aedes japonicus and Aedes ko...
Paolo Catapano
Monica Falcinelli

Paolo Ctapano

and 8 more

May 26, 2023
Recently, two invasive Aedes mosquito species, Ae. japonicus and Ae. koreicus, are circulating in several European countries posing potential health risks to humans and animals. Vector control is the main option to prevent mosquito-borne diseases, and an accurate genome sequence of these mosquitoes is essential to better understand their biology and to develop effective control strategies. Here, we present a de novo genome assembly of the Ae. japonicus (Ajap1) and Ae. koreicus (Akor1) based on a hybrid approach that combines Oxford Nanopore long reads and Illumina short reads data. Their quality was ascertained using various metrics. Masking of repetitive elements, gene prediction and functional annotation was performed. Sequence analysis revealed a very high presence of repetitive DNA and, among others, thermal adaptation genes and insecticide-resistance genes. Through the RNAseq analysis of larvae and adults of Ae. koreicus and Ae. japonicus exposed to different temperatures (15 and 28°C) we also identified genes showing a differential temperature-dependent activation. The assembly of Akor1 and Ajap1 genomes constitutes the first updated collective knowledge of the genomes of both mosquito species, providing the possibility of understanding key mechanisms of their biology such as the ability to adapt to harsh climates and to develop insecticide-resistance mechanisms.
A secretory carcinoma with NTRK3 break-apart molecular rearrangement: A case report o...
Giangiacomo Sanna
Riccardo Nocini

Giangiacomo Sanna

and 6 more

May 26, 2023
A secretory carcinoma with NTRK3 break-apart molecular rearrangement: A case report on a tumor initially diagnosed as a mucoepidermoid carcinoma.Authors declare no conflict of interestData are available from the digital archieves and laboratories of Policlinico G.B. Rossi, Verona, Italy.Key points: Secretory Carcinoma, Salivary Glands, Mucoepidermoid Carcinoma, Oral Oncology, NTRK3
Targeted Ablation of Epicardial Ganglionated Plexi During Cardiac Surgery with Pulsed...
Daniel Musikantow
Vivek Reddy

Daniel Musikantow

and 10 more

May 26, 2023
Background: Modulation of the cardiac autonomic nervous system (ANS) is a promising adjuvant therapy in the treatment of atrial fibrillation (AF). In pre-clinical models, pulsed field (PF) energy has the advantage of selectively ablating the epicardial ganglionated plexi (GP) that govern the ANS. Objective: This study aims to demonstrate the feasibility and safety of epicardial ablation of the GPs with PF during cardiac surgery with a primary efficacy outcome of prolongation of the atrial effective refractory period (AERP).  Methods: In a single-arm, prospective analysis, patients with or without a history of AF underwent epicardial GP ablation with PF during coronary artery bypass grafting (CABG). AERP was determined immediately pre- and post- GP ablation to assess cardiac ANS function. Holter monitors were performed to determine rhythm status and Heart Rate Variability (HRV) at baseline and at 1 month post-procedure.   Conclusions:  This study demonstrates the safety and feasibility of epicardial ablation of the GP using PF to modulate the ANS during cardiac surgery. Large, randomized analyses are necessary to determine whether epicardial PF ablation can offer a meaningful impact on the cardiac ANS and reduce AF. Results: Of 24 patients, 23 (96%) received the full ablation protocol. No device-related adverse effects were noted. GP ablation resulted in a 20.7% ± 19.9% extension in AERP (P < 0.001). Post-operative AF was observed in 7 (29%) patients. Holter monitoring demonstrated an increase in mean heart rate (74.0±8.7 vs 80.6±12.3, P=0.01). There were no significant changes in HRV. There were no study-related complications.
NUMERICAL COMPARISON OF DIFFERENT IMAGING ALGORITHMS.
Soulef BOUGUEROUA
|Noureddine 2,1 DAILI

Soulef BOUGUEROUA

and 1 more

May 26, 2023
Image processing is the set of operations performed to extract “information” from the image. An interesting problem in digital image processing is the restoration of degraded images. It often happens that the resulting image is different from the expected image. Our problem will therefore be to recover an image close to the original image from a poor quality image (that has been skewed by Gaussian and additive noise). There are a lot of algorithms on how we can improve the broken image in better quality. We present in this paper our numerical results obtained with the models of Tichonov regularization, ROF, Vese Osher, anisotropic and isotropic TV denoising algorithms.
Sirolimus-induced DRESS syndrome in a stem cell transplant patient.
Fortunato Cassalia
Alice Spiller

Fortunato Cassalia

and 4 more

May 26, 2023
Title: Sirolimus-induced DRESS syndrome in a stem cell transplant patient.Authors: Fortunato CASSALIA1, Alice SPILLER1, Roberto SALMASO1, Francesca CAROPPO1,2, Anna BELLONI FORTINA1,2Affiliations:Dermatology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.Pediatric Dermatology Unit, Department of Women and Children’s Health, University of Padua, Padua, Italy.Corresponding Author: Francesca Caroppo, MD Unit of Dermatology, Department of Medicine University of Padova, Italy Via Vincenzo Gallucci 4, 35121, Padova, Italy e-mail: francesca.caroppo@outlook.itKeywords:Word count: 1329Tables: NoneFigure: 3References: 9Conflicts of interest: NoneAcknowledgements: NoneAuthor Contributions: All authors contributed to designing and conducting the work, drafting, and revising the manuscript and approved the final version for submission.ABSTRACTBACKGROUND: We present a case of sirolimus-induced DRESS syndrome in a stem cell transplant patient. Sirolimus is an immunosuppressive drug that inhibits the mTOR pathway. It is commonly used in organ transplants to prevent rejection. While no sirolimus-induced DRESS cases have been reported, allergic reactions with everolimus, a similar drug, have been documented. DRESS syndrome is a severe drug reaction characterized by fever, rash, and organ involvement. Diagnosis is based on clinical findings and laboratory tests. Early recognition, discontinuation of the drug, and supportive care are crucial in managing DRESS syndrome, often involving systemic corticosteroids.CASE REPORT A 24-year-old man who had undergone haplo-TESE transplantation for acute lymphatic leukaemia presented with diffuse itchy eczematous lesions. Initially diagnosed as atopic dermatitis, he received topical steroid therapy and NB-UVB phototherapy, but his condition worsened. Two months later, he returned to the emergency department with eczematous patches, xerosis, fever, chills, and generalized edema. His medical history included relapses of leukaemia, acute cutaneous graft-versus-host disease (GVHD), and Evans syndrome. He had been on sirolimus immunosuppressive therapy before the onset of symptoms. A skin biopsy revealed spongiotic dermatitis with dermal eosinophils, suggestive of drug reaction or atopic reaction. Based on the severity of the symptoms and histological findings, the patient was diagnosed with sirolimus-induced DRESS syndrome. Sirolimus was discontinued, and oral steroid therapy was initiated, leading to significant improvement. At the one-month follow-up, the patient was symptom-free and had lost the gained weight.CONCLUSION Although no cases of sirolimus-induced DRESS syndrome have been reported, allergic reactions with eosinophilia induced by everolimus have been documented. And since sirolimus and everolimus, both mTOR inhibitors, share a common mechanism of action, therapeutic indications, pharmacokinetics, adverse effects and drug interactions, it cannot be ruled out that sirolimus may trigger DRESS syndrome in patients with risk factors. In our case, the patient’s history characterized by stem cell transplantation and multiple immunosuppressive therapies may have contributed to the development of DRESS syndrome after beginning sirolimus therapy. This case may be the first evidence of sirolimus-induced DRESS syndrome in a stem cell transplant patient and highlights how early diagnosis, discontinuation of the culprit drug and appropriate management are crucial for a favourable outcome.BACKGROUND We present a case of sirolimus-induced DRESS syndrome1in a stem cell transplant patient. Sirolimus, also known as rapamycin, is an immunosuppressive and antiproliferative drug that inhibits the mammalian target of rapamycin (mTOR) pathway2. It has a wide range of clinical applications and has been extensively studied in various fields of medicine. Sirolimus is commonly used in solid organ transplants to prevent acute rejection and improve transplant survival with the advantage of reducing the nephrotoxicity associated with calcineurin inhibitors3. Although no cases of sirolimus-induced DRESS syndrome have been reported, allergic reactions with eosinophilia induced by everolimus, a similar drug of the mTOR inhibitor family, have been documented. In particular, cases of drug reaction with eosinophilia and systemic symptoms (DRESS) caused by an everolimus-eluting stent have been reported4. DRESS syndrome, also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction characterized by fever, skin rash, multi-organ involvement and eosinophilia. The pathogenesis of the DRESS syndrome remains unclear, involving a complex interaction between drug metabolism, immune dysregulation and genetic factors. Skin manifestations vary from maculopapular eruptions to severe exfoliative dermatitis, while organ involvement often involves the liver, kidneys, lungs and haematological system. Other systemic symptoms may include lymphadenopathy, myocarditis and interstitial nephritis. The diagnosis of DRESS syndrome is based on the recently validated RegiSCAR score5 which considers clinical findings, temporal relationship with drug exposure and blood tests. Early recognition and discontinuation of the involved drug are crucial for the management of DRESS syndrome. Supportive care and careful monitoring of organ function are essential, while symptomatic treatment aims to improve symptoms. Systemic corticosteroids are often administered to suppress the immune response6.CASE REPORTA 24-year-old boy, who had previously undergone haplo-TESE transplantation (transplantation of haploidentical haematopoietic stem cells for acute lymphatic leukaemia, presented to the dermatology outpatient clinic for the onset of a diffuse eruption with itchy eczematous lesions. The initial clinical presentation was diagnosed as atopic dermatitis and topical steroid therapy was recommended. In the following days, due to the lack of clinical response and the worsening of the skin eruption, about two months later the patient returned to the emergency department complaining of diffuse xerosis mixed with eczematous, itchy, finely scaling patches. In addition, the patient complained of fever and chills and significant and consistent oedema all over his body. He also reported a weight gain of 9 kg in the last month and eosinophilia >20% with leukopenia (Figure 1). The medical history revealed that the patient was diagnosed with acute lymphatic leukaemia in 2003 and underwent treatment according to the AIEOP LLA 2000 protocol (Prednisone, Vincristine, Daunorubicin, L-asparaginase, methotrexate, 6-Mercaptopurine, Cyclophosphamide, Cytarabine, Dexamethasone). In 2015, the patient developed a relapse for which he was treated according to the AIEOP protocol BFM 2009 concluded in 2017 (Prednisone, Vincristine, Daunorubicin, L-asparaginase, methotrexate, 6-Mercaptopurine, Cyclophosphamide, Cytarabine, Dexamethasone). However, in 2018, the patient developed a new relapse and therefore underwent haplo-TESE stem cell transplantation. Unfortunately, in 2019, the patient suffered an acute cutaneous GVHD for which he underwent treatment with oral cyclosporine in combination with tacrolimus that led to a rapid improvement of the skin manifestations. Unfortunately, in 2020 he was diagnosed with Evans syndrome and was treated with oral steroids; once the acute phase was over, the patient started immunosuppressive therapy with sirolimus 2 mg/die. Given the history and the severity of the clinical picture, the patient was hospitalized and a skin biopsy with histological examination was performed. The result of the histological examination revealed a hyperkeratosis with focally confluent spongiosis and irregular acanthosis of the epidermide. The underlying superficial dermis shows a modest infiltrate of lymphocytes, plasma cells and eosinophils, the latter also observed in the deep dermis. Specific histochemical stains did not reveal the presence of mucins and fungi (Alcial Blue and PAS) while immunohistochemical reactions for T and B lymphocytes excluded the clinical hypothesis of GVHD. The morphological picture depicts a spongiotic dermatitis with a discrete presence of dermal eosinophils suggesting the possibility of drug reaction vs. atopic reaction (Figure 2). Considering the clinical picture and the histological examination, the diagnosis of DRESS syndrome induced by sirolimus was made7. The drug was withdrawn and scaled-up oral steroid therapy was instituted, after 3 weeks of therapy the patient ceased taking the oral steroid. At the follow-up visit after one month the oedema was in remission, the patient no longer complained of any symptoms and had lost the previously accumulated kg (Figure 3).DISCUSSION The case described presents a 24-year-old boy with a complex medical history, including a previous diagnosis of acute lymphatic leukaemia and subsequent relapses, which required intensive treatments such as stem cell transplantation and immunosuppressive therapy. The patient presented to the dermatology outpatient clinic with diffuse itchy eczematous lesions, initially diagnosed as atopic dermatitis. Despite topical steroid therapy, the patient’s condition worsened with dry, itchy patches mixed with xerosis concomitant with fever, swelling, weight gain and abnormal blood results. Skin biopsy ruled out the diagnosis of graft-versus-host disease (GVHD). Based on the clinical presentation, histological findings and history of sirolimus therapy, the diagnosis of sirolimus-induced DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome was made. Sirolimus was discontinued and the patient started oral steroid therapy, which was gradually reduced and finally discontinued. After three weeks of treatment, the patient’s symptoms improved, including remission of oedema, and at the one-month follow-up visit the patient was asymptomatic and had lost the weight gained during the illness. DRESS syndrome is a severe form of drug reaction in which skin manifestations and systemic involvement are associated. The onset time is usually longer than in other delayed skin reactions, on average 6-8 weeks after the introduction of the responsible drug. It is a severe idiosyncratic T-cell mediated reaction, classified as a type Vb and sometimes IVc delayed hypersensitivity reaction. DRESS is presumed to result from a complex interaction between drug exposure (such as vaccines or biological drugs), genetic predisposition and/or viral reactivation, and the development of this serious clinical condition would appear to be the result of the cumulative effect of aligned risks1. Early recognition and discontinuation of the culprit drug are crucial for the management of DRESS syndrome. Systemic corticosteroids are often used to suppress the inflammatory response and supportive care is provided for any organ involvement6. Although no cases of sirolimus-induced DRESS syndrome are reported in the literature, allergic reactions with eosinophilia induced by everolimus have been described. In particular, cases of drug reaction with eosinophilia and systemic symptom syndrome caused by an everolimus-eluting stent have been reported4. Sirolimus and everolimus both belong to the class of drugs called mTOR inhibitors and share several features8, including: (1) Mechanism of action: Sirolimus and everolimus act by inhibiting the mammalian target of rapamycin (mTOR); (2) therapeutic indications: both are used in immunosuppressive therapy to prevent organ rejection in transplant patients. (3) Pharmacokinetics: both are administered orally and are rapidly absorbed. They have a large volume of distribution and are extensively metabolised in the liver. (4) Adverse effects: They have common adverse effects including immunosuppression, which may increase the risk of infection, delay wound healing and altered response to vaccines. Other potential side effects include hyperlipidaemia (elevated blood lipid levels), peripheral oedema, gastrointestinal disorders, and metabolic abnormalities; (5) drug interactions: both drugs are metabolised by cytochrome P450 enzymes, which may lead to potential drug interactions with other drugs that act on these enzymes9. It is important to consider these interactions when prescribing or administering these drugs. In our case, the patient’s history of previous intensive treatments, stem cell transplantation and immunosuppressive therapies may have contributed to immune system dysregulation and the onset of DRESS syndrome following the initiation of sirolimus therapy. Timely diagnosis, discontinuation of the drug and appropriate management led to the resolution of symptoms and general improvement of the patient’s condition. The case emphasizes the importance of careful monitoring and consideration of potential adverse drug reactions in patients undergoing complex treatment regimes. This case could be the first evidence of DRESS syndrome induced by sirolimus in a stem cell transplant patient.FIGURE 1 Eczematous, itchy, finely scaling patches and significant and consistent oedema.FIGURE 2 Flap of skin with hyperkeratosis, focally confluent spongiosis and irregular acanthosis of the epider-mide. Modest infiltrate of lymphocytes, plasma cells and eosinophils, in the deep dermis.FIGURE 3 One month after withdrawal of SirolimusREFERENCESRamirez, G. A., Ripa, M., Burastero, S., et al . (2023). Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Focus on the Pathophysiological and Diagnostic Role of Viruses. Microorganisms, 11(2), 346.https://doi.org/10.3390/microorganisms11020346Mao, B., Zhang, Q., Ma, L., et al. (2022). Overview of Research into mTOR Inhibitors. Molecules (Basel, Switzerland), 27(16), 5295.https://doi.org/10.3390/molecules27165295Hahn, D., Hodson, E. M., Hamiwka, L. A., et al. (2019). Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients. The Cochrane database of systematic reviews, 12(12), CD004290.https://doi.org/10.1002/14651858.CD004290.pub3Bianchi, L., Caraffini, S., & Lisi, P. (2014). Drug reaction with eosinophilia and systemic symptoms syndrome caused by an everolimus-eluting stent. International journal of dermatology, 53(4), e286–e288.https://doi.org/10.1111/ijd.12112Kardaun, S. H., Sekula, P., Valeyrie-Allanore, L., et al (2013). Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. The British journal of dermatology, 169(5), 1071–1080. https://doi.org/10.1111/bjd.12501Calle, A. M., Aguirre, N., Ardila, et al. (2023). DRESS syndrome: A literature review and treatment algorithm. The World Allergy Organization journal, 16(3), 100673. https://doi.org/10.1016/j.waojou.2022.100673Jindal, R., Chugh, R., Chauhan, P., et al (2022). Histopathological Characterization of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Comparison with Maculopapular Drug Rash (MPDR). Indian dermatology online journal, 13(1), 32–39.https://doi.org/10.4103/idoj.idoj_452_21Yan, X., Huang, S., Yang, Y., et al (2022). Sirolimus or Everolimus Improves Survival After Liver Transplantation for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Granata, S., Dalla Gassa, A., Carraro, A., et al (2016). Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects. International journal of molecular sciences, 17(5), 735. https://doi.org/10.3390/ijms17050735
Detection of colorectal cancer in mice with terahertz technology-determination of an...
Jian Ding
Yong Chen

Jian Ding

and 10 more

May 26, 2023
Colorectal cancer is one of the most prevalent malignancies worldwide, and long-term chronic colitis is considered to be an important factor in the etiological study of colorectal cancer. As an emerging detection technology, the non-invasive, non-ionizing, and fingerprint spectroscopic features of terahertz technology have tremendous application prospects in disease diagnosis. Therefore, this study aims to explore the value of terahertz technology in colitis-related cancers by constructing an inflammation-associated mouse colorectal cancer model. In this paper, we found that the terahertz spectroscopy technique can effectively distinguish colitis-associated cancer from normal tissue, and for the first time, we searched that 1.8 THz may be the best terahertz frequency for diagnosing colorectal cancer in mice, suggesting that we can use the terahertz technique for rapid diagnosis of colorectal cancer histopathology.
On skunk rabies and its prevention in North America
Andres Velasco-Villa

Andres Velasco-Villa

May 26, 2023
The case report by Navarro-Lopez et al., (2023) in this issue describes a thorough differential diagnosis in an equine with acute neurological disease. Rabies was confirmed by direct fluorescent antibody test (DFA). Rabies virus (RABV) was isolated from brain tissue of the ill mare by intracerebral inoculation in sucking mice. Sequencing and phylogenetic inference allowed the identification of the rabies virus variant (RVV) associated with this case. Thus, Navarro-Lopez et al., reported that the rabid mare got infected with a rabies virus variant associated with skunks. This clinical commentary elaborates on the seemingly rare skunk rabies across North America (NA) highlighting its relevance in human and animal health that have remained somehow neglected
Assessment of Agricultural Land Conversion in Vegetable Pocket Areas of Dhading Distr...
Anupam Uprety
Hari Krishna Panta

Anupam Uprety

and 3 more

May 26, 2023
The increasing trend of transformation of land at the expense of fertile agricultural land is becoming troublesome and threatens food security worldwide. The scenario is more severe at the rural-urban interface and the agrarian land on the outskirt of larger cities is at greater risk, however, the extensive literature is not readily available in the Nepalese context. This study focuses on the land use patterns and variables shaping farmers’ choices for the future use of land in Dhading, Nepal. The analysis of land use patterns showed that, between 2013 and 2022, productive agricultural land decreased by 60.28% while non-farm use of land increased by 93.14% in the study area of Dhunibeshi Municipality, Dhading. The cross-sectional survey data among vegetable farming households showed that 36% of the household were eager to switch from farming to non-farm use of their land in the near future. Based on binary logistic regression, land ownership, the share of family income from vegetable production, the proposal received for land conversion, and proximity variables like distance between farmland to the closest non-farm firm, were found to be statistically significant in shaping the farmers’ decisions on agricultural land conversion. The land ownership and lower family income from agriculture activities were identified as major push factors, while the proximity of the farm to non-farm firms, and proposals for urban use of land were identified as major pull factors for land conversion. The widespread adoption of low-cost production strategies in agriculture, and effective implementation of a land-use policy could contribute towards sustainable agricultural land management in the future.
Selective IgM Deficiency presenting as Recurrent Boils: Rare Presentation in a Rarer...
Sowmya Sagireddy
Yuvapriya  Ravikumar

Sowmya Sagireddy

and 4 more

May 26, 2023
A document by Sowmya Sagireddy. Click on the document to view its contents.
Energy-efficient Nanocomputing Circuit by Multiferroic Nanomagnets
Bo Wei
Jia Li

Bo Wei

and 6 more

May 26, 2023
Magnetoelastic switching in multiferroic nanomagnets with a small voltage is a promising substitute for current charge-based CMOS devices. Here, we study strain-mediated multiferroic majority logic gate by solving Landau-Lifshitz-Gilbert equation and establish an energy- efficient CMOS compatible equivalent circuit analogy to capacitor's I- V characteristics. We can easily simulate nanomagnet logic units using this tool. After that, the circuit is verified by SPICE simulations. Results show that the output voltage polarity is determined by the majority of input voltage polarity with ultralow energy consumption, working similarly to majority logic function. The SPICE circuit model shows ultralow energy consumption because of the conserved dynamic current, which can serve as a promising logic unit, consequently, integrated into large-scale nanomagnetic logic circuits and even a nanomagnetic chip.
Multiple urinary peptides display distinct sex-specific distribution
Ioanna Mina
Emmanouil Mavrogeorgis

Ioanna Mina

and 6 more

May 26, 2023
Previous studies have established the association of sex with gene and protein expression. This study investigated the association of sex with the abundance of endogenous urinary peptides, using capillary electrophoresis-coupled to mass spectrometry datasets from 2008 healthy individuals and patients with type II diabetes, divided in one discovery and two validation cohorts. Statistical analysis using the Mann-Whitney test, adjusted for multiple testing, revealed 143 sex-associated peptides in the discovery cohort. Of these, 90 peptides were associated with sex in at least one of the validation cohorts and showed agreement in their regulation trends across all cohorts. The 90 sex-associated peptides were fragments of 29 parental proteins. Comparison with previously published transcriptomics data demonstrated that the genes encoding 16 of these parental proteins had sex-biased expression. The 143 sex-associated peptides were combined into a support vector machine-based classifier that could discriminate males from females in two independent sets of healthy individuals and patients with type II diabetes, with an AUC of 89% and 81%, respectively. Collectively, the urinary peptidome contains multiple sex-associated differences, which may enable a better understanding of sex-biased molecular mechanisms and the development of more accurate diagnostic, prognostic or predictive classifiers for each individual sex.
Admixture mapping and selection scans identify genomic regions associated with stomat...
Karl Fetter
Stephen Keller

Karl Fetter

and 1 more

May 26, 2023
Variation in fitness components can be linked in some cases to variation of key traits. Metric traits that lie at the intersection of development, defense, and ecological interactions may be expected to experience strong environmental selection, informing our understanding of evolutionary and ecological processes. Here, we use quantitative genetic and population genomic methods to investigate disease dynamics in hybrid and non-hybrid populations. We focus our investigation on morphological and ecophysiological traits which inform our understanding of physiology, growth, and defense against a pathogen. In particular, we investigate stomata, microscopic pores on the surface of a leaf which regulate gas exhange during photosynthesis and are sites of entry for various plant pathogens. Stomatal patterning traits were highly predictive of disease risk. Admixture mapping identified a polygenic basis of disease resistance. Candidate genes for stomatal and disease resistance map to the same genomic regions, and are experienceing positive selection. Genes with functions for guard cell homeostasis, the plant immune system, components of constitutive defenses, and growth related transcription factors were identified. Our results indicate positive selection is filtering genetic variance from one of the parental species maladpated to a novel pathogen, and changing suites of stomatal traits which contribute to disease variation in natural populations.
Charles Bonnet Syndrome in an elderly blind man with recurrent Pituitary Macroadenoma...
Suluma Aslan
Gloria Ngajilo

Suluma Aslan

and 2 more

May 26, 2023
INTRODUCTIONCharles Bonnet Syndrome(CBS) was first described in 1760 by Naturalist and philosopher Charles Bonnet, who first observed lifelike complex visual hallucinations in his grandfather Charles Lullis after bilateral cataract surgery(1); it was a neurologist George de Morsier who coined the term in 1938 after Charles Bonnet himself developed the condition(2). CBS, also known as ”phantom image”, is characterized by recurrent or persistent complex visual hallucinations in people with a disease of the visual system with intact insight, intellectual function and normal cognitive functioning without primary psychiatric disorders(3,4). With limited knowledge of CBS among physicians, the prevalence of CBS is underreported(4) even though 41-59% of the visually impaired experience elementary visual phenomena, and 11-15% exhibit complex hallucinations, due to a medical condition or artificially produced, such as in preparation for cataract surgery(5,6). The presence of varying inclusion criteria, inconsistent depth of questioning and limited patient disclosure for fear of being ridiculed may all contribute to underreporting(3,5). Visual hallucinations could be a sign of psychiatric disorders, neurological diseases, metabolic abnormalities, and the use or abuse of specific drugs(7). Both elementary forms(3) and complex visual hallucinations are reported in CBS(8); while glaucoma,cataract and age-related macular degeneration are the most common associated disorders, any ophthalmological conditions can lead to CBS(7), especially in significant visual impairment(9). A pituitary adenoma is rarely associated with CBS (10); however, reduced visual acuity or a visual field deficit can occur from the benign tumour’s compressing optic chiasm affecting one or both eyes(11).There are three main theories associated with the pathogenesis of CBS, and these are; the sensory deprivation or deafferentiation theory related to spontaneous excitation due to a loss of visual input to the brain(12), the release theory associated with excessive excitation and the consequent release of visual hallucinations(13,14), and the ”irritative theory” due to distal provocative injuries transmit abnormal input to the visual cortex leading to abnormal excitatory activity to the temporal and occipital lobes(15,16).Charles Bonnet syndrome is treated multifacetedly with pharmacotherapy, psychosocial therapy, maintaining appropriate eye care, and sensory stimulation. Generally, CBS is treated with antipsychotics and antidepressants(5), and in some cases, antiepileptic medications have also been used with variable benefits (17).An 81-year-old blind male presented with a three-year history of visual hallucinations after a recurrence of pituitary macroadenoma. His past psychiatric history is uneventful, and he has intact insight with no cognitive impairment. He improved on a low haloperidol dosage, with a few relapses, when he stops the medications.
In silico identification of gene targets to enhance C12 fatty acid production in Esch...
Paul Matthay
Kenneth Simoens

Paul Matthay

and 7 more

May 26, 2023
The global interest in fatty acids is steadily rising due to their wealth of industrial potential ranging from cosmetics to biofuels. Unfortunately, certain fatty acids, such as monounsaturated C12, cannot be produced cost and energy-efficiently using conventional methods. Biosynthesis of fatty acids using microorganisms can overcome this drawback. However, rewiring a microbe’s metabolome for increased production remains challenging. To overcome this, sophisticated genome-wide metabolic network models have become available. These models predict the effect of genetic perturbations on the metabolism, thereby serving as a guide for metabolic pathways optimization. In this work, we used constraint-based modeling in combination with the algorithm Optknock to identify gene deletions in Escherichia coli that improve the C12 fatty acid production. Nine gene targets were identified that, when deleted, were predicted to increase C12 titers. Targets play a role in anaplerotic reactions, amino acid synthesis, carbon metabolism and cofactor-balancing. Subsequently, we constructed the corresponding (combinatorial) deletion mutants to validate the in silico predictions in vivo. Our highest producer (Δ maeB Δ ndk Δ pykA) reaches a titer of 6.7 mg/L, corresponding to a 7.5-fold increase in C12 fatty acid production. This study demonstrates that model-guided metabolic engineering is a useful tool to improve C12 fatty acid production.
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