ARISCAT and LAS VEGAS risk scores for predicting postoperative pulmonary complications after cardiac surgery: a cohort study.

Background: Postoperative pulmonary complications (PPCs) could lead to morbidity, mortality, and prolonged hospital stay. Different risk-scoring systems are used to predict the identification of patients at risk of developing PPCs. The diagnostic accuracies of the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) and Local Assessment of Ventilatory Management During General Anaesthesia for Surgery (LAS VEGAS) risk scores are compared in prediction of PPCs taking pulmonary complication as the gold standard in cardiac surgery. Materials and methods: A prospective cohort study with consecutive sampling technique. A total of 181 patients were included. Quantitative data is presented as simple descriptive statistics giving mean and standard deviation, and qualitative variables are presented as frequency and percentages. Sensitivity, specificity, positive and negative predictive values, and diagnostic accuracies are also calculated. Results: Total 181 post-cardiac surgery patients were analyzed. The median [interquartile range] of age, height, weight, and BMI were 60.0 [52.0-67.0] years, 163.0 [156.0-168.0] cm, 71.0 [65.0-80.0] kg and 27.3 [24.2-30.4] kg/m2. 127 (70.2%) were male, and 54 (29.8%) were female. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of ARISCAT for the prediction of PPCs were (94.9%, 4.65%, 76.1%, 22.9% and 73.4%), whereas LAS VEGAS were (97.1%, 4.65%, 76.5%, 33.3% and 75.1%), respectively. Conclusion: Both the ARISCAT and LAS VEGAS risk scores are of limited value in cardiac surgery patients for the prediction of postoperative pulmonary complications, based on the predicted scores in this study.

Clinical phenotype and management of sound-induced pain: Insights from adults with pain hyperacusis.

Pain hyperacusis, also known as noxacusis, causes physical pain in response to everyday sounds that do not bother most people. How sound causes excruciating pain that can last for weeks or months in otherwise healthy individuals is not well understood, resulting in a lack of effective treatments. To address this gap, we identified the most salient physical and psychosocial consequences of debilitating sound-induced pain and reviewed the interventions that sufferers have sought for pain relief to gain insights into the underlying mechanisms of the condition. Adults (n = 32) with pain hyperacusis attended a virtual focus group to describe their sound-induced pain. They completed three surveys to identify common symptoms and themes that defined their condition and to describe their use of pharmaceutical and non-pharmaceutical therapies for pain relief. All participants endorsed negative effects of pain hyperacusis on psychosocial and physical function. Most reported sound-induced burning (80.77%), stabbing (76.92%), throbbing (73.08%), and pinching (53.85%) that occurs either in the ear or elsewhere in the body (i.e., referred pain). Participants reported using numerous pharmaceutical and non-pharmaceutical interventions to alleviate their pain with varying degrees of pain relief. Benzodiazepines and nerve blockers emerged as the most effective analgesic options while non-pharmaceutical therapies were largely ineffective. Symptoms of pain hyperacusis and therapeutic approaches are largely consistent with peripheral mechanistic theories of pain hyperacusis (e.g., trigeminal nerve involvement). An interdisciplinary approach to clinical studies and the development of animal models is needed to identify, validate, and treat the pathological mechanisms of pain hyperacusis.

ephrin-B2 promotes nociceptive plasticity and hyperalgesic priming through EphB2-MNK-eIF4E signaling in both mice and humans.

Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE2 injection either to the paw or the cranial dura. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1 knockout mice) and by eFT508, a specific MNK inhibitor. Sensory neuron-specific knockout of EphB2 using Pirt-Cre demonstrated that ephrin-B2 actions require this receptor. In Ca2+-imaging experiments on cultured DRG neurons, ephrin-B2 treatment enhanced Ca2+ transients in response to PGE2 and these effects were absent in DRG neurons from MNK1-/- and EphB2-PirtCre mice. In experiments on human DRG neurons, ephrin-B2 increased eIF4E phosphorylation and enhanced Ca2+ responses to PGE2 treatment, both blocked by eFT508. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling, offering new insight into how ephrin-B signaling promotes pain.

Single stage cricoid split laryngoplasty with costochondral rib grafting is a novel approach to treat subglottic stenosis in a paediatric patient: A case report.

INTRODUCTION AND IMPORTANCE: Subglottic stenosis (SGS) appears to be a commonly encountered condition in the paediatric age group. Single stage cricoid split laryngoplasty with costochondral rib grafting in paediatric patients is a unique, innovative, and advanced operation in nature. Morbidity and mortality rates can be minimized with early diagnosis and prompt treatment. PRESENTATION OF CASE: Presenting the case of a 13-month-old child diagnosed with Grade II SGS who was managed for cricoid split laryngoplasty with a costochondral rib graft. It was a unique strategy for providing infants and neonates with symptomatic SGS with a safe and efficient substitute for long-term tracheostomy. When healing was completed, the patient regained the function of their airway. The approach was successful, and preventable to long-term tracheostomy. DISCUSSION: Performing this procedure early in children has shown higher rates of success and it is safe and effective. Further extensive research and studies need to be conducted in this domain, and every patient's status should be reviewed time and again to tend to their specific needs, and the choice of procedure should be made optimally based on clinical evaluations. CONCLUSION: Successful management of a 13-month-old child with Grade II subglottic stenosis through cricoid split laryngoplasty with costochondral rib grafting is a challenging and novel approach to treating single-stage SGS.

Loss of Sigma-2 Receptor/TMEM97 Is Associated with Neuropathic Injury-Induced Depression-Like Behaviors in Female Mice.

Previous studies have shown that ligands that bind to sigma-2 receptor/TMEM97 (s2R/TMEM97), a transmembrane protein, have anxiolytic/antidepressant-like properties and relieve neuropathic pain-like effects in rodents. Despite medical interest in s2R/TMEM97, little affective and pain behavioral characterization has been done using transgenic mice, which limits the development of s2R/TMEM97 as a viable therapeutic target. Using wild-type (WT) and global Tmem97 knock-out (KO) mice, we sought to identify the contribution of Tmem97 in modulating affective and pain-like behaviors using a battery of affective and pain assays, including open field, light/dark preference, elevated plus maze, forced swim test, tail suspension test, and the mechanical sensitivity tests. Our results demonstrate that female Tmem97 KO mice show less anxiety-like and depressive-like behaviors in light/dark preference and tail suspension tests but not in an open field, elevated plus maze, and forced swim tests at baseline. We next performed spared nerve injury in WT and Tmem97 KO mice to assess the role of Tmem97 in neuropathic pain-induced anxiety and depression. WT mice, but not Tmem97 KO mice, developed a prolonged neuropathic pain-induced depressive-like phenotype when tested 10 weeks after nerve injury in females. Our results show that Tmem97 plays a role in modulating anxiety-like and depressive-like behaviors in naive animals with a significant change in the presence of nerve injury in female mice. Overall, these data demonstrate that Tmem97 could be a target to alleviate affective comorbidities of pain disorders.

Addressing cyberbullying in Urdu tweets: a comprehensive dataset and detection system.

The prevalence of cyberbullying has reached an alarming rate, affecting approximately 54% of teenagers who experience various forms of cyberbullying, including offensive hate speech, threats, and racism. This research introduces a comprehensive dataset and system for cyberbullying detection in Urdu tweets, leveraging a spectrum of machine learning approaches including traditional models and advanced deep learning techniques. The objectives of this study are threefold. Firstly, a dataset consisting of 12,500 annotated tweets in Urdu is created, and it is made publicly available to the research community. Secondly, annotation guidelines for Urdu text with appropriate labels for cyberbullying detection are developed. Finally, a series of experiments is conducted to assess the performance of machine learning and deep learning techniques in detecting cyberbullying. The results indicate that fastText deep learning models outperform other models in cyberbullying detection. This study demonstrates its efficacy in effectively detecting and classifying cyberbullying incidents in Urdu tweets, contributing to the broader effort of creating a safer digital environment.

Nerve Detection and Visualization Using Hyperspectral Imaging for Surgical Guidance.

During surgery of delicate regions, differentiation between nerve and surrounding tissue is crucial. Hyperspectral imaging (HSI) techniques can enhance the contrast between types of tissue beyond what the human eye can differentiate. Whereas an RGB image captures 3 bands within the visible light range (e.g., 400 nm to 700 nm), HSI can acquire many bands in wavelength increments that highlight regions of an image across a wavelength spectrum. We developed a workflow to identify nerve tissues from other similar tissues such as fat, bone, and muscle. Our workflow uses spectral angle mapper (SAM) and endmember selection. The method is robust for different types of environment and lighting conditions. We validated our workflow on two samples of human tissues. We used a compact HSI system that can image from 400 to 1700 nm to produce HSI of the samples. On these two samples, we achieved an intersection-over-union (IoU) segmentation score of 84.15% and 76.73%, respectively. We showed that our workflow identifies nerve segments that are not easily seen in RGB images. This method is fast, does not rely on special hardware, and can be applied in real time. The hyperspectral imaging and nerve detection approach may provide a powerful tool for image-guided surgery.

Gender disparities and predictors of in-hospital mortality with Takotsubo cardiomyopathy.

BACKGROUND: Takotsubo cardiomyopathy (TCM) is classically associated with significant gender disparities, such that it is more prevalent in females, but the clinical outcomes are worse for male patients. The goal of this study was to assess contemporary gender disparities in clinical outcomes of TCM hospitalizations and to determine predictors of male in-hospital mortality. METHODS: This was a retrospective analysis involving adult hospitalizations for TCM in the U.S between 2016 and 2020. Multivariable Logistic regression was used to estimate Odds Ratio (OR) for in-hospital mortality between the two genders. Univariable Cox regression was performed to identify predictors associated with in-hospital mortality for male hospitalizations. All factors from the univariable analysis with p < 0.20 were included in a multivariable Cox regression model. RESULTS: A total of 199,920 patients with TCM were identified. Female patients with TCM had 50% lower risk of in-hospital mortality compared to male patients (Adjusted OR 0.50, 95% CI 0.46-0.55, p < 0.001). Older age, higher Charlson comorbidity index, history of intracranial hemorrhage, cardiac arrest, need for vasopressor agents, mechanical intubation, and cardiogenic shock without the use of temporary mechanical circulatory support (MCS) were associated with higher in-hospital male mortality. CONCLUSIONS: Although TCM is more prevalent among females, gender disparities exist in the clinical outcomes of TCM patients. Cardiac arrest and cardiogenic shock without the use of temporary MCS were found to be the most significant predictors of male in-hospital mortality. Cardiogenic shock with use of temporary MCS did not lead to higher male in-hospital mortality.

A Comparison of Techniques of Internal Jugular Vein Cannulation: Anatomical Landmark, Ultrasound Guided Pre-location, and Real-Time Ultrasound Guided.

OBJECTIVE: The objective of our study is to compare the success rate, duration, and incidence of complications of a right internal jugular vein (IJV) cannulation by using three different techniques. METHODOLOGY: A randomised controlled trial was conducted at a tertiary care teaching hospital. A total of 201 patients were randomly allocated to one of the following three groups (67 in each group). Techniques were categorised as anatomical landmark technique group (Group ALT), ultrasound guided pre-location group (Group USG-Pre), and real-time ultrasound-guided technique group (Group USG-RT). INTERVENTIONS: Central venous catheter insertion via three techniques. RESULTS: In 138 (73.01%) patients' IJV canulated in the first attempt, USG-RT, USG-Pre, and ALT were 51 (83.6%), 44 (72.1%), and 43 (64.2%), respectively. On the other hand, 37 (19.57%) patients were required in the second attempt, while only 14 (7.40%) patients were required in the third attempt for successful IJV cannulation. The success rates, as defined in our study, were only 138 (73%) as, in 51 (27%), we cannulated in more than a single attempt or switched to another technique. We found a significant difference in preparation time in all techniques as P-value <0.05, but no significant difference was found in venous access time, cannulation time, and duration of the procedure. CONCLUSIONS: Any technique can be used for IJV cannulation, but the most acceptable is the real-time US technique. However, no difference in the overall procedure time among all three techniques was noted, and no major incidence of complication was found.

Cutaneous signs of selected cardiovascular disorders: A narrative review.

Cardiovascular diseases are the leading cause of mortality and morbidity globally. Clinicians must know cutaneous signs of cardiovascular disease, including petechiae, macules, purpura, lentigines, and rashes. Although cutaneous manifestations of diseases like infectious endocarditis and acute rheumatic fever are well established, there is an indispensable need to evaluate other important cardiovascular diseases accompanied by cutaneous signs. Moreover, discussing the latest management strategies in this regard is equally imperative. This review discusses distinctive skin findings that help narrow the diagnosis of cardiovascular diseases and recommendations on appropriate treatment.

Unlocking the potential of biochar in the remediation of soils contaminated with heavy metals for sustainable agriculture.

Agricultural soils contaminated with heavy metals (HMs) impose a threat to the environmental and to human health. Amendment with biochar could be an eco-friendly and cost-effective option to decrease HMs in contaminated soil. This paper reviews the application of biochar as a soil amendment to immobilise HMs in contaminated soil. We discuss the technologies of its preparation, their specific properties, and effect on the bioavailability of HMs. Biochar stabilises HMs in contaminated soil, enhance the overall quality of the contaminated soil, and significantly reduce HM uptake by plants, making it an option in soil remediation for HM contamination. Biochar enhances the physical (e.g. bulk density, soil structure, water holding capacity), chemical (e.g. cation exchange capacity, pH, nutrient availability, ion exchange, complexes), and biological properties (e.g. microbial abundance, enzymatic activities) of contaminated soil. Biochar also enhances soil fertility, improves plant growth, and reduces the plant availability of HMs. Various field studies have shown that biochar application reduces the bioavailability of HMs from contaminated soil while increasing crop yield. The review highlights the positive effects of biochar by reducing HM bioavailability in contaminated soils. Future work is recommended to ensure that biochars offer a safe and sustainable solution to remediate soils contaminated with HMs.

Investigating the Efficacy of Zinc and Vitamin A in Treating Pediatric Community-Acquired Pneumonia.

BACKGROUND: Community-acquired pneumonia (CAP) poses a significant global health challenge, even more so for children less than five years old. Nutritional interventions, such as zinc and vitamin A supplementation, are gaining attention for their therapeutic potential in enhancing recovery and minimizing pneumonia severity in pediatric patients. OBJECTIVE: To assess the therapeutic benefits of zinc and vitamin A supplementation in pediatric CAP patients under five years old and to advocate for their use in clinical settings. METHODOLOGY: Three groups were formed in a randomized controlled trial conducted from October 2022 to September 2023, to address zinc and vitamin A supplementation in pediatric patients under five years old in the intensive care unit with severe pneumonia. Group 1 received zinc supplementation, group 2 received vitamin A supplementation, and group 3 served as the control group, receiving antibiotic treatment exclusively for pneumonia. This treatment comprised either a ß-lactam (amoxicillin-clavulanate, commonly referred to as Augmentin) administered orally at 500 mg/125 mg three times a day, Augmentin 875 mg/125 mg orally twice daily, or Augmentin 2000 mg/125 mg orally once daily. Additionally, the control group received a macrolide (azithromycin or clarithromycin) or doxycycline at a dosage of 100 mg orally twice daily. Linear regression analysis identified statistically significant decreases in both length of hospital stay and active pneumonic effusion. RESULTS: The study encompassed 90 pediatric pneumonia patients with an age range of six to 55 months. Multiple linear regression analysis showed that both vitamin A and zinc led to a significant decrease in hospitalization length by 2.39 days (p < 0.01, 95% CI: 4.19-0.47) and 3.17 days (p < 0.01, 95% CI: 5.19-1.31), respectively. In comparison to the control group, both the vitamin A and zinc supplementation groups were linked to a shorter pneumonic effusion duration (p < 0.001). CONCLUSION: Both interventions significantly reduced the duration of hospitalization (2.39 days for vitamin A and 3.17 days for zinc) and pneumonic effusion compared to the control group. These findings highlight the potential of zinc and vitamin A as valuable additions to standard CAP treatment regimens, potentially leading to improved clinical outcomes and reduced healthcare burdens.

Sleep Pattern Changes in Patients Who Are Scheduled for Cardiac Surgery.

Introduction Surgery patients frequently experience sleep deprivation, which is regarded as a stress factor during the perioperative period and can cause physical discomfort, exhaustion, and even postoperative pain. There is a dearth of information on preoperative sleep habits and the consequences that may result. There are both subjective and objective ways to rate the quality of your sleep. We chose the Pittsburgh Sleep Quality Index (PSQI), which employs a questionnaire to provide crucial information on issues like sleep length, efficiency, and interruption. Lower sleep quality is correlated with higher PSQI scores. Study objective Our study aimed to assess the changes in the sleep pattern of cardiac disease patients before cardiac surgery and compare these changes with baseline sleep patterns. Methods This prospective survey was carried out after ethical review committee approval at the Department of Anesthesia, Aga Khan University Hospital. Consent was obtained from all patients undergoing cardiac surgery. Strict inclusion and exclusion criteria were followed. All patients aged 25 to 65 who came from home for elective cardiac surgery under general anesthesia were included. At the same time, patient demographics were noted. Additionally, a printed PSQI questionnaire was distributed to each participant. The native Urdu language was also translated into this questionnaire. The patient was given an explanation of this form by a medical professional. This questionnaire was filled out by the patients on the surgical floor or preoperative area before premedication. The PSQI questionnaire was used to assess baseline sleeping patterns, and then the same questions were asked about the period between decisions for the date of surgery and the time of admission for surgery. Results A total of 83 patients participated in the study. The mean age of the patient was 57 (±13.0), out of which 67 (80.7%) were males and 16 (19.3%) were females. The most common surgeries were coronary artery bypass (CABG) surgery 63 (77.8%), followed by valve replacement nine (11.1%). The overall mean PSQI score was higher (5.27) once the surgery date was decided as compared to the baseline (4.84), but it did not reach the statistically significant level (p-value 0.411). Sleep latency (time to fall asleep while in bed) was the only variable statistically significant between baseline (26.1 (±35.0) and after the surgery date has been finalized (36.1 (±46.6)). No significant differences were found in other variables like sleep quality (feeling of being well-rested), sleep duration (hours of actual sleep), sleep efficiency (sleep efficiency is the ratio of the amount of total time asleep versus the total time in bed), and sleep disturbance (problem initiating and maintaining sleep). Total bedtime was also reduced at night before surgery but did not achieve a significant level. The logistic regression model demonstrated that age, gender, and type of surgery did not influence sleep quality. Conclusion In the present study, lower sleep quality was observed before cardiac surgery, but it did not reach a statistically significant level when compared with baseline. Sleep latency (time to fall asleep while in bed) was significantly prolonged compared to baseline. We could not find any association between quality of sleep and variables like age, gender, and type of surgery.

Preparation, optimization and evaluation of Osthole transdermal therapeutic system.

In the current study, the solubility and permeability of Osthole-loaded microemulsion were enhanced, which increased bioavailability. In addition, Carbomer 940 was added for prolonged drug delivery. The microemulsion was prepared after the screening of Kukui oil, Labrasol (surfactant), and transcutol-P (co-surfactant). Pseudoternary phase diagrams were employed to find the microemulsion region. Box Behnken Design (BBD) was employed for optimizing microemulsions. Variables were related and compared using mathematical equations and response surface plots (RSP). MEBG was then compared with control gel on the basis of stability studies, drug permeation, skin irritation studies, and anti-inflammatory studies. Microemulsion preparations depicted a pH of 5.27 - 5.80, a conductivity of 139 - 185 µS/cm, a poly-dispersity index of 0.116 - 0.388, a refractive index of 1.330 - 1.427, an average droplet size of 64 - 89 nm, homogeneity, spherical shape, viscosity 52 - 185 cP. Predicted values of Optimized microemulsions showed more reasonable agreement than experimental values. The microemulsion was stable and non-irritating on Rabbit skin. MEBG showed a significant difference from control gel for percent edema inhibition from the standard. The permeation enhancing capability of MEBG using a suitable viscosity fabricates it promising carrier for transdermal delivery of Osthole.

Highly specific σ2R/TMEM97 ligand FEM-1689 alleviates neuropathic pain and inhibits the integrated stress response.

The sigma 2 receptor (σ2R) was described pharmacologically more than three decades ago, but its molecular identity remained obscure until recently when it was identified as transmembrane protein 97 (TMEM97). We and others have shown that σ2R/TMEM97 ligands alleviate mechanical hypersensitivity in mouse neuropathic pain models with a time course wherein maximal antinociceptive effect is approximately 24 h following dosing. We sought to understand this unique antineuropathic pain effect by addressing two key questions: do these σ2R/TMEM97 compounds act selectively via the receptor, and what is their downstream mechanism on nociceptive neurons? Using male and female conventional knockout mice for Tmem97, we find that a σ2R/TMEM97 binding compound, FEM-1689, requires the presence of the gene to produce antinociception in the spared nerve injury model in mice. Using primary mouse dorsal root ganglion neurons, we demonstrate that FEM-1689 inhibits the integrated stress response (ISR) and promotes neurite outgrowth via a σ2R/TMEM97-specific action. We extend the clinical translational value of these findings by showing that FEM-1689 reduces ISR and p-eIF2α levels in human sensory neurons and that it alleviates the pathogenic engagement of ISR by methylglyoxal. We also demonstrate that σ2R/TMEM97 is expressed in human nociceptors and satellite glial cells. These results validate σ2R/TMEM97 as a promising target for further development for the treatment of neuropathic pain.

S. aureus drives itch and scratch-induced skin damage through a V8 protease-PAR1 axis.

Itch is an unpleasant sensation that evokes a desire to scratch. The skin barrier is constantly exposed to microbes and their products. However, the role of microbes in itch generation is unknown. Here, we show that Staphylococcus aureus, a bacterial pathogen associated with itchy skin diseases, directly activates pruriceptor sensory neurons to drive itch. Epicutaneous S. aureus exposure causes robust itch and scratch-induced damage. By testing multiple isogenic bacterial mutants for virulence factors, we identify the S. aureus serine protease V8 as a critical mediator in evoking spontaneous itch and alloknesis. V8 cleaves proteinase-activated receptor 1 (PAR1) on mouse and human sensory neurons. Targeting PAR1 through genetic deficiency, small interfering RNA (siRNA) knockdown, or pharmacological blockade decreases itch and skin damage caused by V8 and S. aureus exposure. Thus, we identify a mechanism of action for a pruritogenic bacterial factor and demonstrate the potential of inhibiting V8-PAR1 signaling to treat itch.

Unrevealing the potential of microbes in decomposition of organic matter and release of carbon in the ecosystem.

Organic matter decomposition is a biochemical process with consequences affecting climate change and ecosystem productivity. Once decomposition begins, C is lost as CO2 or sequestered into more recalcitrant carbon difficult to further degradation. As microbial respiration releases carbon dioxide into the atmosphere, microbes act as gatekeepers in the whole process. Microbial activities were found to be the second largest CO2 emission source in the environment after human activities (industrialization), and research investigations suggest that this may have affected climate change over the past few decades. It is crucial to note that microbes are major contributors in the whole C cycle (decomposition, transformation, and stabilization). Therefore, imbalances in the C cycle might be causing changes in the entire carbon content of the ecosystem. The significance of microbes, especially soil bacteria in the terrestrial carbon cycle requires more attention. This review focuses on the factors that affect microorganism behavior during the breakdown of organic materials. The key factors affecting the microbial degradation processes are the quality of the input material, nitrogen, temperature, and moisture content. In this review, we suggest that to address global climate change and its effects on agricultural systems and vice versa, there is a need to double-up on efforts and conduct new research studies to further evaluate the potential of microbial communities to reduce their contribution to terrestrial carbon emission.

Windows malware detection based on static analysis with multiple features.

Malware or malicious software is an intrusive software that infects or performs harmful activities on a computer under attack. Malware has been a threat to individuals and organizations since the dawn of computers and the research community has been struggling to develop efficient methods to detect malware. In this work, we present a static malware detection system to detect Portable Executable (PE) malware in Windows environment and classify them as benign or malware with high accuracy. First, we collect a total of 27,920 Windows PE malware samples divided into six categories and create a new dataset by extracting four types of information including the list of imported DLLs and API functions called by these samples, values of 52 attributes from PE Header and 100 attributes of PE Section. We also amalgamate this information to create two integrated feature sets. Second, we apply seven machine learning models; gradient boosting, decision tree, random forest, support vector machine, K-nearest neighbor, naive Bayes, and nearest centroid, and three ensemble learning techniques including Majority Voting, Stack Generalization, and AdaBoost to classify the malware. Third, to further improve the performance of our malware detection system, we also deploy two dimensionality reduction techniques: Information Gain and Principal Component Analysis. We perform a number of experiments to test the performance and robustness of our system on both raw and selected features and show its supremacy over previous studies. By combining machine learning, ensemble learning and dimensionality reduction techniques, we construct a static malware detection system which achieves a detection rate of 99.5% and error rate of only 0.47%.

Comprehensive Review of Hypertensive Disorders Related to Pregnancy.

Hypertensive disorder of pregnancy is a common complication during pregnancy that affects approximately 10% of pregnancies and is responsible for nearly 14% of maternal deaths worldwide. It affects the mother and the fetus simultaneously, sometimes putting the health of the mother and the fetus at odds with each other. It may present with only hypertension and proteinuria or with life-threatening complications in the mother such as eclampsia; stroke; acute pulmonary edema; acute renal failure; disseminated intravascular coagulation; placental abruption; hemolysis, elevated liver enzymes, and low platelet syndrome; pregnancy loss; and fetal growth restriction and prematurity resulting from the frequent need of delivering preterm in the fetus. In this review, we aimed to describe hypertensive disorders of pregnancy, mainly preeclampsia and chronic hypertension in pregnancy, by discussing the pathophysiology, the central role of abnormal placentation, the release of antiangiogenic factors in the circulation and immunological factors, the clinical outcome in the mother and the fetus, and the diagnostic criteria and principles of management of both the conditions. We also discuss possible screening methods and prevention of preeclampsia using low-dose aspirin and eclampsia prophylaxis.

Highly specific σ2R/TMEM97 ligand alleviates neuropathic pain and inhibits the integrated stress response.

The Sigma 2 receptor (σ2R) was described pharmacologically more than three decades ago, but its molecular identity remained obscure until recently when it was identified as transmembrane protein 97 (TMEM97). We and others have shown that σ2R/TMEM97 ligands alleviate mechanical hypersensitivity in mouse neuropathic pain models with a time course wherein maximal anti-nociceptive effect is approximately 24 hours following dosing. We sought to understand this unique anti-neuropathic pain effect by addressing two key questions: do these σ2R/TMEM97 compounds act selectively via the receptor, and what is their downstream mechanism on nociceptive neurons? Using male and female conventional knockout (KO) mice for Tmem97, we find that a new σ2R/TMEM97 binding compound, FEM-1689, requires the presence of the gene to produce anti-nociception in the spared nerve injury model in mice. Using primary mouse dorsal root ganglion (DRG) neurons, we demonstrate that FEM-1689 inhibits the integrated stress response (ISR) and promotes neurite outgrowth via a σ2R/TMEM97-specific action. We extend the clinical translational value of these findings by showing that FEM-1689 reduces ISR and p-eIF2α levels in human sensory neurons and that it alleviates the pathogenic engagement of ISR by methylglyoxal. We also demonstrate that σ2R/TMEM97 is expressed in human nociceptors and satellite glial cells. These results validate σ2R/TMEM97 as a promising target for further development for the treatment of neuropathic pain.