bluuebunny/crossref_metadata_2025 huggingface dataset:
Circulating plasma IL-13 and periostin are dysregulated type 2 inflammatory biomarkers in prurigo nodularis: A cluster analysis
Authors: Parthasarathy Varsha , Cravero Karen , Deng Junwen , Sun Zhe , Engle Sarah M. , Auxier Autum N. , Hahn Nathan , Sims Jonathan T. , Okragly Angela J. , Alphonse Martin P. , Kwatra Shawn G.
Published: December 2022

Importance

Prurigo nodularis (PN) is a chronic heterogeneous inflammatory skin disease.

Objective

To elucidate which components of type 2 inflammation are dysregulated systemically in PN.

Design

Whole blood was obtained from PN patients with uncontrolled disease and control patients without pruritus. Plasma was assayed for IL-4, IL-5, IL-13, IgE, and periostin. ANOVA was utilized to compare PN and control patients and multiple-hypothesis adjusted p-value was calculated with the significance threshold at 0.05. Clustering was performed using K-means clustering.

Participants

PN patients (n = 29) and controls (n = 18) from Johns Hopkins Dermatology had similar age sex, and race distributions.

Results

Single-plex assays of the biomarkers demonstrated elevated circulating plasma IL-13 (0.13 vs. 0.006 pg/mL, p = 0.0008) and periostin (80.3 vs. 60.2 ng/mL, p = 0.012) in PN compared to controls. IL-4 (0.11 vs. 0.02 pg/mL, p = 0.30) and IL-5 (0.75 vs. 0.40 pg/mL, p = 0.10) were not significantly elevated, while IgE approached significance (1202.0 vs. 432.7 ng/mL, p = 0.08). Clustering of PN and control patients together revealed two clusters. Cluster 1 (n = 36) consisted of 18 PN patients and 18 controls. Cluster 2 (n = 11) consisted entirely of PN patients (p < 0.01). Cluster 2 had higher levels of IL-13 (0.33 vs. 0.008 pg/mL, p = 0.0001) and IL-5 (1.22 vs. 0.43 pg/mL, p = 0.03) compared to cluster 1.

Conclusion and relevance

This study demonstrates elevation of IL-13 and periostin in the blood of PN patients, with distinct clusters with varying degrees of type 2 inflammation. Given this heterogeneity, future precision medicine approaches should be explored in the management of PN.
Prostate specific membrane antigen binding radiopharmaceuticals: Current data and new concepts
Authors: Sartor Oliver , Baghian Ali
Published: December 2022

Prostate specific membrane antigen (PSMA) represents a validated target for prostate cancer therapeutics. The phase III VISION study with 177lutetium (177Lu)-PSMA-617 represented a pivotal step forward and the FDA has now approved this agent in advanced metastatic castrate-resistant prostate cancer (mCRPC). A number of other PSMA targeted radiopharmaceuticals are now under development. Some of these agents are targeted to PSMA via monoclonal antibodies such as J591 and TLX591. Others are targeted to PSMA via small molecules such as PSMA-617, PSMA I&T, MIP-1095, etc. In addition to the use of various ligands, multiple isotopes are now in clinical trials. Beta emitters in development include 177Lu, 131iodide (131I), and 67copper (67Cu). Targeted alpha emitters potentially include 225actinium (225Ac), 227thorium (227Th), and 212lead (212Pb). Phase III trials are underway with both 177Lu-PSMA-617 and 177Lu-PSMA I&T in mCRPC. Single dose phase I trials are complete with 225Ac-J591 but additional data are need to launch a phase III. Data are promising with 225Ac-PSMA-617 but concerns remain over salivary and renal toxicity. Tandem therapies are also considered combining both beta and alpha-targeted therapy. Taken together the field of PSMA targeted radiopharmaceuticals is rapidly developing. The targeted alpha therapies are particularly promising and several developmental paths forward are being considered in the near future.
Clinical and biochemical characteristics of people experiencing post-coronavirus disease 2019-related symptoms: A prospective follow-up investigation
Authors: Alfadda Assim A. , Rafiullah Mohamed , Alkhowaiter Mohammad , Alotaibi Naif , Alzahrani Musa , Binkhamis Khalifa , Siddiqui Khalid , Youssef Amira , Altalhi Haifa , Almaghlouth Ibrahim , Alarifi Mohammed , Albanyan Saleh , Alosaimi Mohammed F. , Isnani Arthur , Nawaz Shaik Sarfaraz , Alayed Khalid
Published: December 2022

Background

Post-acute coronavirus disease 2019 (COVID-19) syndrome, also known as long COVID, is a prolonged illness after the acute phase of COVID-19. Hospitalized patients were known to have persisting symptoms of fatigue, headache, dyspnea, and anosmia. There is a need to describe the characteristics of individuals with post-COVID-19 symptoms in comparison to the baseline characteristics.

Purpose

To investigate the clinical and biochemical characteristics of people who recovered from COVID-19 after 6 months of discharge from the hospital.

Methods

This was a prospective follow-up investigation of hospitalized and discharged COVID-19 patients. Adult patients admitted to King Saud University Medical City, Riyadh, Saudi Arabia, with laboratory-confirmed COVID-19 and discharged were recruited. The baseline demographic information, comorbidities, vital signs and symptoms, laboratory parameters, COVID-19 therapy, and outcomes were collected from the medical records. Blood samples were collected for cytokines estimation. A detailed interview about signs and symptoms was undertaken during the follow-up.

Results

Half of the followed-up people reported experiencing at least one of the COVID-19-related symptoms. The mean blood pressure was found higher in follow-up. People with the symptoms were characterized by low lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without any post-COVID-19 symptoms. Cytokines IL-8, VEGF, and MCP-1 were higher in people with the most frequent symptoms.

Conclusion

People with post-COVID-19 symptoms were characterized by lower lymphocyte count, lower serum calcium levels, and hyperglycemia compared to people without symptoms. Individuals with the most frequent post-COVID-19 symptoms had higher baseline pro-inflammatory, chemotactic, and angiogenic cytokines.
Letrozole as premedication of high intensity focused ultrasound treatment of uterine fibroids: A retrospective observation study
Authors: Chen Wei-Chun , Hsu Chia-Chen , Huang Huei-Jean , Cheng Wei-Jen , Chang Ting-Chang , Chou Hung-Hsueh
Published: December 2022

Background

No reports on Letrozole as a pretreatment before ablation of uterine fibroid with high intensity focused ultrasound (HIFU), so a retrospective observation study was performed to evaluate the response of different pre-HIFU medication.

Methods

We collected patients with single uterine fibroid receiving HIFU ablation from January 2018 to April 2021. All enrolled patients were classified into three group: group A (no pre-HIFU medication use), group B (Pre-HIFU letrozole use), group C (pre-HIFU gonadotrophin releasing hormone analog, GnRHa). Further associated clinical data and treatment response after HIFU treatment were reviewed and evaluated.

Results

A total of 39 patients including 21, 7, and 11 in group A, B, and C were collected respectively. After pre-HIFU medication, no difference of fibroid volume was found (A: 251.4, B: 360.6, C: 409.4 cm3, p = 0.250), and GnRHa group had significantly larger volume reduction than Letrozole users (38.6% vs. 16.4%, p = 0.007). The incidence of hypoestrogenic symptoms was higher in GnRHa group than in letrozole users (27.3% vs. 0, p = 0.170). GnRHa group had more sonication time (p = 0.001), treatment duration (p = 0.002), and ablated energy (p = 0.001) than group A and B. The treatment efficiency was higher in letrozole group than that in other 2 groups (4.52 vs. 2.39 vs. 2.34 cm3/min, p = 0.050). For patients with fibroid over 10 cm in diameter, letrozole group had even better energy efficiency (p = 0.067), treatment speed (p = 0.007), treatment efficiency (p = 0.001), NPV per energy (p = 0.005), and NPV per sonication (p = 0.004) than other 2 groups.

Conclusion

Letrozole as a pretreatment medication before HIFU treatment might increase the energy efficiency and treatment efficiency of its ablation of uterine leiomyoma, especially for fibroid over 10 cm. Future study of larger patient number is needed to confirm our results.
Spirituality in people with advanced chronic obstructive pulmonary disease – challenge for more effective interventions, support, and healthcare education: Mini-review
Authors: Kotlińska-Lemieszek Aleksandra , Fopka-Kowalczyk Małgorzata , Krajnik Małgorzata
Published: December 2022

More recently there has been a growing interest in spirituality in medicine, especially in the field of palliative care, oncology, intensive care, and cardiology. However, according to literature, it seems to be a limited number of researches on how healthcare professionals should provide spiritual care (SC) for people with non-malignant lung diseases and what kind of education for them enables them to do it efficiently. This mini-review aims to provide an overview of current knowledge of an area of spirituality and SC for people with advanced chronic obstructive pulmonary disease, including spiritual well-being and religious/spiritual coping, their relations with the quality of life and symptom burden, exercise capacity and daily functioning, mental health, or medication adherence. It also analyses the use of interventions to meet patients’ spiritual needs and patients’ expectations regarding SC provided by professional careers. Based on the literature authors try to show the fields that should be improved and proposed future research directions.
A capsule network-based method for identifying transcription factors
Authors: Zheng Peijie , Qi Yue , Li Xueyong , Liu Yuewu , Yao Yuhua , Huang Guohua
Published: December 2022

Transcription factors (TFs) are typical regulators for gene expression and play versatile roles in cellular processes. Since it is time-consuming, costly, and labor-intensive to detect it by using physical methods, it is desired to develop a computational method to detect TFs. Here, we presented a capsule network-based method for identifying TFs. This method is an end-to-end deep learning method, consisting mainly of an embedding layer, bidirectional long short-term memory (LSTM) layer, capsule network layer, and three fully connected layers. The presented method obtained an accuracy of 0.8820, being superior to the state-of-the-art methods. These empirical experiments showed that the inclusion of the capsule network promoted great performances and that the capsule network-based representation was superior to the property-based representation for distinguishing between TFs and non-TFs. We also implemented the presented method into a user-friendly web server, which is freely available at http://www.biolscience.cn/Capsule_TF/ for all scientific researchers.
Gut microbiota composition in COVID-19 hospitalized patients with mild or severe symptoms
Authors: Mazzarelli Antonio , Giancola Maria Letizia , Fontana Andrea , Piselli Pierluca , Binda Elena , Trivieri Nadia , Mencarelli Gandino , Marchioni Luisa , Vulcano Antonella , De Giuli Chiara , Panebianco Concetta , Villani Annacandida , Copetti Massimiliano , Perri Francesco , Fontana Carla , Nicastri Emanuele , Pazienza Valerio
Published: December 2022

Background and aim

COVID-19, the infectious disease caused by SARS-CoV-2 virus that has been causing a severe pandemic worldwide for more than 2 years, is characterized by a high heterogeneity of clinical presentations and evolution and, particularly, by a varying severity of respiratory involvement. This study aimed to analyze the diversity and taxonomic composition of the gut microbiota at hospital admission, in order to evaluate its association with COVID-19 outcome. In particular, the association between gut microbiota and a combination of several clinical covariates was analyzed in order to characterize the bacterial signature associate to mild or severe symptoms during the SARS-CoV-2 infection.

Materials and methods

V3–V4 hypervariable region of 16S rRNA gene sequencing of 97 rectal swabs from a retrospective cohort of COVID-19 hospitalized patients was employed to study the gut microbiota composition. Patients were divided in two groups according to their outcome considering the respiratory supports they needed during hospital stay: (i) group “mild,” including 47 patients with a good prognosis and (ii) group “severe,” including 50 patients who experienced a more severe disease due to severe respiratory distress that required non-invasive or invasive ventilation. Identification of the clusters of bacterial population between patients with mild or severe outcome was assessed by PEnalized LOgistic Regression Analysis (PELORA).

Results

Although no changes for Chao1 and Shannon index were observed between the two groups a significant greater proportion of Campylobacterota and Actinobacteriota at phylum level was found in patients affected by SARS-CoV-2 infection who developed a more severe disease characterized by respiratory distress requiring invasive or non-invasive ventilation. Clusters have been identified with a useful early potential prognostic marker of the disease evolution.

Discussion

Microorganisms residing within the gut of the patients at hospital admission, were able to significantly discriminate the clinical evolution of COVID-19 patients, in particular who will develop mild or severe respiratory involvement. Our data show that patients affected by SARS-CoV-2 with mild or severe symptoms display different gut microbiota profiles which can be exploited as potential prognostic biomarkers paving also the way to new integrative therapeutic approaches.
Differences in gut microbes in captive pangolins and the effects of captive breeding
Authors: Jiao Wenjing , Liu Lina , Zeng Zhiliao , Li Linmiao , Chen Jinping
Published: December 2022

Intestinal microorganisms are crucial for health and have a significant impact on biological processes, such as metabolism, immunity, and neural regulation. Although pangolin are protected animals in China and listed as critically endangered (CR) level by The International Union for Conservation of Nature (IUCN), the population of wild pangolins has decreased sharply in recent decades. Captive breeding has been adopted to protect pangolins, but the survival is low due to gastrointestinal infections, diarrhea, and parasitic infections. Studies on intestinal microbes in pangolins may reveal the relationship between intestinal microorganisms and health and assist protection. To explore the relationship between intestinal microorganisms and pangolin health, blood parameters and intestinal microorganisms of 10 pangolins (two Manis pentadactyla and eight Manis javanica) were studied at the Shenzhen Wildlife Rescue Center. There is difference among adult Sunda pangolins (M. javanica), adult Chinese pangolins (M. pentadactyla) and sub-adult Sunda pangolins (M. javanica) in intestinal microbial composition, diversity and phenotypic diversity, which suggested that adult Sunda pangolins occupied more diversity and proportion of microbial species to resist environmental pressure than the others. Due to the captive breeding serum cortisol of pangolins was increased, and the intestinal microbial structure changed, which may affect immunity. This study provides a scientific basis for the rescue of pangolins through artificial breeding.
Metabolic activity and community structure of prokaryotes associated with particles in the twilight zone of the South China Sea
Authors: Liu Hao , Wang Fangzhou , Liu Hongbin , Jing Hongmei
Published: December 2022

The twilight zone is an important depth of the ocean where particulate organic matter (POM) remineralization takes place, and prokaryotes contribute to more than 70% of the estimated remineralization. However, little is known about the microbial community and metabolic activity associated with different particles in the twilight zone. The composition and distribution of particle-attached prokaryotes in the twilight zone of the South China Sea (SCS) were investigated using high-throughput sequencing and quantitative PCR, together with the Biolog Ecoplate™ microplates culture to analyze the microbial metabolic activity. We found that α- and γ-Proteobacteria dominating at the lower and upper boundary of the twilight zone, respectively; Methanosarcinales and Halobacteriales of the Euyarchaeota occupied in the larger particles at the upper boundary. Similar microbial community existed between euphotic layer and the upper boundary. Higher amount of shared Operational Taxonomic Units (OTUs) in the larger particles along the water depths, might be due to the fast sinking and major contribution of carbon flux of the larger particles from the euphotic layer. In addition to polymers as the major carbon source, carbohydrates and amino acids were preferentially used by microbial community at the upper and lower boundary, respectively. This could potentially be attributed to the metabolic capabilities of attached microbial groups in different particles, and reflected the initial preference of the carbon source by the natural microbes in the twilight zone as well. The microbial structure and carbon metabolic profiles could be complemented with metatranscriptomic analysis in future studies to augment the understanding of the complex carbon cycling pathways in the twilight zone.
Infusing zeta inhibitory peptide into the perirhinal cortex of rats abolishes long-term object recognition memory without affecting novel object location recognition
Authors: Augereau Keanan , Migues Paola V. , Hardt Oliver
Published: December 2022

Infusing the amnesic agent zeta inhibitory peptide (ZIP) into the dorsal hippocampus disrupts established long-term object location recognition memory without affecting object identity recognition, which likely depends on the perirhinal cortex. Here, we tested whether infusing ZIP into the perirhinal cortex can abolish long-term memory supporting object identity recognition, leaving long-term object location recognition memory intact. We infused ZIP into the perirhinal cortex of rats either 1 day or 6 days after exposing them to two identical objects in an open field arena. One day after ZIP infusion, that is, 2 or 7 days after object exposure, we either assessed whether the animals recognized that now one of the two objects was novel or whether they recognized that one of the two familiar objects was at a new location. Our results show for both retention intervals, infusions of ZIP into the perirhinal cortex impaired novel object recognition but spared novel object location recognition. Rats that received a scrambled version of ZIP had no deficit in either test at both retention intervals and expressed stronger novel object recognition compared to rats infused with ZIP. These findings support the view that object recognition depends on dissociable memory representations distributed across different brain areas, with perirhinal cortex maintaining long-term memory for what objects had been encountered, and hippocampus supporting memory for where these objects had been placed.
Spontaneous Object Exploration in a Recessive Gene Knockout Model of Parkinson’s Disease: Development and Progression of Object Recognition Memory Deficits in Male Pink1–/– Rats
Authors: Pinizzotto Claudia C. , Dreyer Katherine M. , Aje Oluwagbohunmi A. , Caffrey Ryan M. , Madhira Keertana , Kritzer Mary F.
Published: December 2022

Cognitive impairments appear at or before motor signs in about one third of patients with Parkinson’s disease (PD) and have a cumulative prevalence of roughly 80% overall. These deficits exact an unrelenting toll on patients’ quality and activities of daily life due in part to a lack of available treatments to ameliorate them. This study used three well-validated novel object recognition-based paradigms to explore the suitability of rats with knockout of the PTEN-induced putative kinase1 gene (Pink1) for investigating factors that induce cognitive decline in PD and for testing new ways to mitigate them. Longitudinal testing of rats from 3–9 months of age revealed significant impairments in male Pink1–/– rats compared to wild type controls in Novel Object Recognition, Novel Object Location and Object-in-Place tasks. Task-specific differences in the progression of object discrimination/memory deficits across age were also seen. Finally, testing using an elevated plus maze, a tapered balance beam and a grip strength gauge showed that in all cases recognition memory deficits preceded potentially confounding impacts of gene knockout on affect or motor function. Taken together, these findings suggest that knockout of the Pink1 gene negatively impacts the brain circuits and/or neurochemical systems that support performance in object recognition tasks. Further investigations using Pink1–/– rats and object recognition memory tasks should provide new insights into the neural underpinnings of the visual recognition memory and visuospatial information processing deficits that are often seen in PD patients and accelerate the pace of discovery of better ways to treat them.
Transformer-based progressive residual network for single image dehazing
Authors: Yang Zhe , Li Xiaoling , Li Jinjiang
Published: December 2022

Introduction

The seriously degraded fogging image affects the further visual tasks. How to obtain a fog-free image is not only challenging, but also important in computer vision. Recently, the vision transformer (ViT) architecture has achieved very efficient performance in several vision areas.

Methods

In this paper, we propose a new transformer-based progressive residual network. Different from the existing single-stage ViT architecture, we recursively call the progressive residual network with the introduction of swin transformer. Specifically, our progressive residual network consists of three main components: the recurrent block, the transformer codecs and the supervise fusion module. First, the recursive block learns the features of the input image, while connecting the original image features of the original iteration. Then, the encoder introduces the swin transformer block to encode the feature representation of the decomposed block, and continuously reduces the feature mapping resolution to extract remote context features. The decoder recursively selects and fuses image features by combining attention mechanism and dense residual blocks. In addition, we add a channel attention mechanism between codecs to focus on the importance of different features.

Results and discussion

The experimental results show that the performance of this method outperforms state-of-the-art handcrafted and learning-based methods.
Case report: Clinical report of co-occurrence of pituitary adenoma and meningioma in the sellar region after meningioma treatment
Authors: Lu Wang , Shengkai Yang , Yu Wang , Aimin Li , Shiwei Yan , Kang Xie
Published: December 2022

The coexistence of meningioma and pituitary adenoma is very rare, especially in the same location after meningioma surgery. Here, we reported a case of coexisting meningioma and pituitary adenoma secondary to postoperative meningioma in the sellar region in a patient who had not received radiation therapy before the second surgery. A 61-year-old woman underwent craniotomy for tumor resection for sellar meningioma in 2017, and postoperative imaging showed no residual in the surgical area. In 2022, the patient had a history of decreased vision again. MRI showed the possibility of postoperative pituitary adenoma in the sellar region. The patient underwent endoscopic resection of the skull base lesion again. After surgery, the patient's visual symptoms improved. Histology of the sellar tumor showed both meningioma (meningeal epithelial type and WHO grade I) and pituitary adenoma in the same section. The coexistence of meningioma and pituitary adenoma is a very rare surgical entity. This report provides a theoretical basis for the selection of intracerebral tumor surgery and provides a diagnostic basis and treatment reference for patients diagnosed with meningioma and pituitary adenoma at the same time.
Assessment of cognitive impairment after acute cerebral infarction with T1 relaxation time measured by MP2RAGE sequence and cerebral hemodynamic by transcranial Doppler
Authors: Yan Hongting , Chen Honghai , Liu Yanzhi , Zhang Qiannan , Guo Yunchu , Fu Yu , Ren Hongling , Wang Hairong , Wang Chun , Ge Yusong
Published: December 2022

Objective

This study aimed to investigate early brain microstructural changes discovered using magnetization-prepared two rapid acquisition gradient echo (MP2RAGE) sequence and cerebral hemodynamic using TCD for cognitive impairment after acute cerebral infarction.

Methods

We enrolled 43 patients with acute cerebral infarction and 21 healthy people in the study, who were subjected to cognitive assessments, the MP2RAGE sequence, and a cerebral hemodynamic examination. A total of 26 brain regions of interest were investigated. Furthermore, we used cerebral hemodynamics to explain brain microstructural changes, which helped us better understand the pathophysiology of cognitive impairment after acute cerebral infarction and guide treatment.

Results

T1 relaxation times in the left frontal lobe, right frontal lobe, right temporal lobe, left precuneus, left thalamus, right hippocampus, right head of caudate nucleus, and splenium of corpus callosum were substantially different across the three groups, which were significantly correlated with neuropsychological test scores. CI group patients had significantly lower cerebral blood flow velocity than those in the N-CI and Normal groups. The receiver operating curve analysis revealed that most T1 relaxation times had high sensitivity and specificity, especially on the right temporal lobe and right frontal lobe. There was a potential correlation between T1 relaxation times and MMSE scores through TCD parameters.

Conclusion

The MP2RAGE sequence can detect alterations in whole brain microstructure in patients with cognitive impairment after acute cerebral infarction. Brain microstructural changes could influence cognitive function through cerebral hemodynamics. T1 relaxation times on the right temporal lobe and the right frontal lobe are expected to be a prospective biomarker of cognitive impairment after acute cerebral infarction.
Evaluating the effects of low-dose simulated galactic cosmic rays on murine hippocampal-dependent cognitive performance
Authors: Simmons Pilar , Trujillo Madison , McElroy Taylor , Binz Regina , Pathak Rupak , Allen Antiño R.
Published: December 2022

Space exploration has advanced substantially over recent decades and plans to increase the duration of deep space missions are in preparation. One of the primary health concerns is potential damage to the central nervous system (CNS), resulting in loss of cognitive abilities and function. The majority of ground-based research on space radiation-induced health risks has been conducted using single particle simulations, which do not effectively model real-world scenarios. Thus, to improve the safety of space missions, we must expand our understanding of the effects of simulated galactic cosmic rays (GCRs) on the CNS. To assess the effects of low-dose GCR, we subjected 6-month-old male BALB/c mice to 50 cGy 5-beam simplified GCR spectrum (1H, 28Si, 4He, 16O, and 56Fe) whole-body irradiation at the NASA Space Radiation Laboratory. Animals were tested for cognitive performance with Y-maze and Morris water maze tests 3 months after irradiation. Irradiated animals had impaired short-term memory and lacked spatial memory retention on day 5 of the probe trial. Glial cell analysis by flow cytometry showed no significant changes in oligodendrocytes, astrocytes, microglia or neural precursor cells (NPC’s) between the sham group and GCR group. Bone marrow cytogenetic data showed a significant increase in the frequency of chromosomal aberrations after GCR exposure. Finally, tandem mass tag proteomics identified 3,639 proteins, 113 of which were differentially expressed when comparing sham versus GCR exposure (fold change > 1.5; p < 0.05). Our data suggest exposure to low-dose GCR induces cognitive deficits by impairing short-term memory and spatial memory retention.
Recognizing novel drugs against Keap1 in Alzheimer’s disease using machine learning grounded computational studies
Authors: Mukerjee Nobendu , Al-Khafaji Khattab , Maitra Swastika , Suhail Wadi Jaafar , Sachdeva Punya , Ghosh Arabinda , Buchade Rahul Subhash , Chaudhari Somdatta Yashwant , Jadhav Shailaja B. , Das Padmashree , Hasan Mohammad Mehedi , Rahman Md. Habibur , Albadrani Ghadeer M. , Altyar Ahmed E. , Kamel Mohamed , Algahtani Mohammad , Shinan Khlood , Theyab Abdulrahman , Abdel-Daim Mohamed M. , Ashraf Ghulam Md. , Rahman Md. Mominur , Sharma Rohit
Published: December 2022

Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world, affecting an estimated 50 million individuals. The nerve cells become impaired and die due to the formation of amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs). Dementia is one of the most common symptoms seen in people with AD. Genes, lifestyle, mitochondrial dysfunction, oxidative stress, obesity, infections, and head injuries are some of the factors that can contribute to the development and progression of AD. There are just a few FDA-approved treatments without side effects in the market, and their efficacy is restricted due to their narrow target in the etiology of AD. Therefore, our aim is to identify a safe and potent treatment for Alzheimer’s disease. We chose the ursolic acid (UA) and its similar compounds as a compounds’ library. And the ChEMBL database was adopted to obtain the active and inactive chemicals against Keap1. The best Quantitative structure-activity relationship (QSAR) model was created by evaluating standard machine learning techniques, and the best model has the lowest RMSE and greatest R2 (Random Forest Regressor). We chose pIC50 of 6.5 as threshold, where the top five potent medicines (DB06841, DB04310, DB11784, DB12730, and DB12677) with the highest predicted pIC50 (7.091184, 6.900866, 6.800155, 6.768965, and 6.756439) based on QSAR analysis. Furthermore, the top five medicines utilize as ligand molecules were docked in Keap1’s binding region. The structural stability of the nominated medications was then evaluated using molecular dynamics simulations, RMSD, RMSF, Rg, and hydrogen bonding. All models are stable at 20 ns during simulation, with no major fluctuations observed. Finally, the top five medications are shown as prospective inhibitors of Keap1 and are the most promising to battle AD.
Evaluating the effects of curcumin nanomicelles on clinical outcome and cellular immune responses in critically ill sepsis patients: A randomized, double-blind, and placebo-controlled trial
Authors: Karimi Arash , Pourreza Sanaz , Vajdi Mahdi , Mahmoodpoor Ata , Sanaie Sarvin , Karimi Mozhde , Tarighat-Esfanjani Ali
Published: December 2022

Introduction

In sepsis, the immune system is overreacting to infection, leading to organ dysfunction and death. The purpose of this study was to investigate the impacts of curcumin nanomicelles on clinical outcomes and cellular immune responses in critically ill sepsis patients.

Method

For 10 days, 40 patients in the intensive care units (ICU) were randomized between the nano curcumin (NC) and placebo groups in a randomized study. We evaluated serum levels of biochemical factors, inflammatory biomarkers, the mRNA expression levels of FOXP3, NLRP-3, IFN-γ, and NF-κp genes in the PBMCs, and clinical outcomes before the beginning of the supplementation and on days 5 and 10.

Results

NLR family pyrin domain containing 3 (NLRP3), interferon gamma (IFN-γ), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression levels significantly P = 0.014, P = 0.014, and P = 0.019, respectively) decreased, but forkhead box P3 (FOXP3) mRNA expression levels increased significantly (P = 0.008) in the NC group compared to the placebo group after 10 days. NC supplementation decreased serum levels of IL-22, IL-17, and high mobility group box 1 (HMGB1) (P < 0.05). Nevertheless, biochemical factors and nutritional status did not differ significantly (P > 0.05). NC supplementation resulted in decreased sequential organ failure assessment and multiple organ dysfunction syndromes scores, while it did not have significant impacts on length of stay in the ICU, systolic blood pressure, diastolic blood pressure, a saturation of oxygen (%), and respiratory rate (breaths/min) PaO2/FiO2 (p > 0.05).

Conclusion

For critically ill patients with sepsis, NC supplementation may be an effective therapeutic strategy. More randomized clinical trials involving longer follow-up periods and different doses are needed to achieve the best results.
Vitality, fermentation, aroma profile, and digestive tolerance of the newly selected Lactiplantibacillus plantarum and Lacticaseibacillus paracasei in fermented apple juice
Authors: Liang Jia Rui , Deng Hong , Hu Ching Yuan , Zhao Peng Tao , Meng Yong Hong
Published: December 2022

Background

To enrich the probiotic lactic acid bacteria (LAB) strains and expand the commercialization of new fermented juice products, we have identified two LAB strains with excellent potential in fermenting apple juice from pickles.

Methods

The two strains were morphologically, physiologically, and genetically characterized. The strains’ fermentation performance and alterations in volatile aroma components of apple juice and ability to survive in a simulated gastrointestinal environment were evaluated.

Results

Two strains were identified as Lacticaseibacillus paracasei (WFC 414) and Lactiplantibacillus plantarum (WFC 502). The growth of WFC 414 and WFC 502 in apple juice for 48 h reached 8.81 and 9.33 log CFU/mL, respectively. Furthermore, 92% and 95% survival rates were achieved in 2 h simulated gastric juice, and 80.7 and 83.6% survival rates in 4 h simulated intestinal juice. During the fermentation, WFC 414 and WFC 502 reduced the soluble sugars and total polyphenols in apple juice, and consumed malic acid to produce large amounts of lactic acid (3.48 and 5.94 mg/mL). In addition, the esters and aldehydes were reduced, and the production of alcohols, acids and ketones was elevated in the apple juice fermented by both strains.

Conclusion

These results show that WFC 414 and WFC 502 have great potential applications in the fermented fruit juice industry.
Mushrooms as future generation healthy foods
Authors: Bell V. , Silva C. R. P. G. , Guina J. , Fernandes T. H.
Published: December 2022

The potential of edible mushrooms as an unexploited treasure trove, although rarely included in known food guidelines, is highlighted. Their role in shielding people against the side effects of an unhealthy stylish diet is reviewed. Mushrooms complement the human diet with various bioactive molecules not identified or deficient in foodstuffs of plant and animal sources, being considered a functional food for the prevention of several human diseases. Mushrooms have been widely used as medicinal products for more than 2,000 years, but globally the potential field of use of wild mushrooms has been untapped. There is a broad range of edible mushrooms which remain poorly identified or even unreported which is a valuable pool as sources of bioactive compounds for biopharma utilization and new dietary supplements. Some unique elements of mushrooms and their role in preventative healthcare are emphasized, through their positive impact on the immune system. The potential of mushrooms as antiviral, anti-inflammatory, anti-neoplastic, and other health concerns is discussed. Mushrooms incorporate top sources of non-digestible oligosaccharides, and ergothioneine, which humans are unable to synthesize, the later a unique antioxidant, cytoprotective, and anti-inflammatory element, with therapeutic potential, approved by world food agencies. The prebiotic activity of mushrooms beneficially affects gut homeostasis performance and the balance of gut microbiota is enhanced. Several recent studies on neurological impact and contribution to the growth of nerve and brain cells are mentioned. Indeed, mushrooms as functional foods' nutraceuticals are presently regarded as next-generation foods, supporting health and wellness, and are promising prophylactic or therapeutic agents.
Malnutrition diagnosed by the Global Leadership Initiative on Malnutrition criteria predicting survival and clinical outcomes of patients with cancer: A systematic review and meta-analysis
Authors: Peng Dadi , Zong Kezhen , Yang Hang , Huang Zuotian , Mou Tong , Jiang Puen , Wu Zhongjun
Published: December 2022

Objectives

Recently, some cohorts have looked into the use of Global Leadership Initiative on Malnutrition (GLIM) criteria in cancer patients. The objective of the current meta-analysis was to determine its utility in predicting clinical and survival outcomes for cancer patients.

Method

Searching and screening literature from PubMed, Web of Science and Embase until September 13, 2022 was performed by two researchers independently. According to the exclusion and inclusion criteria, articles reporting the impact of malnutrition diagnosed by GLIM on long-term survival and clinical outcomes were included. Data of interest were also extracted from the included papers. The stability of the pooled results was evaluated using sensitivity analysis. With the aid of subgroup analysis, heterogeneity was revealed. To assess publication bias, Egger’s and Begg’s tests were conducted. The influence of publication bias on the pooling risk estimate was examined using a trim-and-fill analysis.

Results

15 studies that qualified for our study were identified. Pooled hazard ratio (HR) from both multivariate and univariate regression analysis showed a worse overall survival in GLIM-defined malnourished cancer patients than those in well-nourished status. Meanwhile, disease-free survival was also poorer in malnourished patients. Moreover, pooled odds ratio (OR) demonstrated that malnourished cancer patients were more likely to develop overall postoperative complications, complications ≥ Clavien-Dindo grade IIa and complications ≥ Clavien-Dindo grade IIIa. Two articles reported negative relation between GLIM-defined malnutrition and 30-day readmission/mortality.

Conclusion

GLIM-defined malnutrition possesses value in predicting poorer survival and clinical outcomes for cancer patients.

Systematic review registration

[https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=321094], identifier [CRD42022321094].
Nomograms predict survival benefits of radical prostatectomy and chemotherapy for prostate cancer with bone metastases: A SEER‐based study
Authors: Sun Donglin , Lin Ao , Sun Zhun , Yang Shuqi , Sun Yuexin , Chen Anning , Qian Guojun , Ji Zhonghua , Wang Li
Published: December 2022

Purpose

This study aimed to identify independent prognosis-associated factors of bone-metastatic prostate cancer. The nomograms were further developed to obtain indicators for the prognostic evaluation.

Methods

A total of 7315 bone-metastatic prostate cancer (PCa) patients from 2010 to 2016 were retrospectively collected from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were randomly divided into the training cohort (n=5,120) and test cohort (n=2,195) in a ratio of 7:3. Univariate and multivariate Cox regression models were applied to evaluate potential risk factors. A 1:1 propensity score matching (PSM) was further performed to decrease the confounding effect and re-evaluate the influence of radical prostatectomy and chemotherapy on prognosis. Combining these potential prognosis factors, the nomograms of cancer-specific survival (CSS) and overall survival (OS) at different times were established. C-indexes, calibration curves, and decision curves were developed to evaluate the discrimination, calibration, and clinical benefit of the nomograms.

Results

Eleven independent prognosis factors for CSS and twelve for OS were utilized to conduct the nomograms respectively. The C-indexes of nomograms for CSS and OS were 0.712 and 0.702, respectively. A favorable consistency between the predicted and actual survival probabilities was demonstrated by adopting calibration curves. Decision curves also exhibited a positive clinical benefit of the nomograms.

Conclusions

Nomograms were formulated successfully to predict 3-year and 5-year CSS and OS for bone-metastatic PCa patients. Radical prostatectomy and chemotherapy were strongly associated with the bone-metastatic PCa prognosis.
Case report: Fractional brain tumor burden magnetic resonance mapping to assess response to pulsed low-dose-rate radiotherapy in newly-diagnosed glioblastoma
Authors: Amidon Ryan F. , Santos-Pinheiro Fernando , Straza Michael , Prah Melissa A. , Mueller Wade M. , Krucoff Max O. , Connelly Jennifer M. , Kleefisch Christopher J. , Coss Dylan J. , Cochran Elizabeth J. , Bovi Joseph A. , Schultz Christopher J. , Schmainda Kathleen M.
Published: December 2022

Background

Pulsed low-dose-rate radiotherapy (pLDR) is a commonly used reirradiation technique for recurrent glioma, but its upfront use with temozolomide (TMZ) following primary resection of glioblastoma is currently under investigation. Because standard magnetic resonance imaging (MRI) has limitations in differentiating treatment effect from tumor progression in such applications, perfusion-weighted MRI (PWI) can be used to create fractional tumor burden (FTB) maps to spatially distinguish active tumor from treatment-related effect.

Methods

We performed PWI prior to re-resection in four patients with glioblastoma who had undergone upfront pLDR concurrent with TMZ who had radiographic suspicion for tumor progression at a median of 3 months (0-5 months or 0-143 days) post-pLDR. The pathologic diagnosis was compared to retrospectively-generated FTB maps.

Results

The median patient age was 55.5 years (50-60 years). All were male with IDH-wild type (n=4) and O6-methylguanine-DNA methyltransferase (MGMT) hypermethylated (n=1) molecular markers. Pathologic diagnosis revealed treatment effect (n=2), a mixture of viable tumor and treatment effect (n=1), or viable tumor (n=1). In 3 of 4 cases, FTB maps were indicative of lesion volumes being comprised predominantly of treatment effect with enhancing tumor volumes comprised of a median of 6.8% vascular tumor (6.4-16.4%).

Conclusion

This case series provides insight into the radiographic response to upfront pLDR and TMZ and the role for FTB mapping to distinguish tumor progression from treatment effect prior to redo-surgery and within 20 weeks post-radiation.
The immune checkpoint expression in the tumor immune microenvironment of DLBCL: Clinicopathologic features and prognosis
Authors: Ma Jiajia , Pang Xuelian , Li Junna , Zhang Wei , Cui Wenli
Published: December 2022

Background & aims

The immune checkpoint recently provides a new strategy for the immunotherapy of malignant tumors. However, the role in the immune microenvironment of DLBCL is not completely clear.

Methods

We detected the expression of PD-1, LAG-3, TIM-3, and TIGIT on TILs and on tumor cells among 174 DLBCL patients by IHC.

Results

In TILs, the positive rates of PD-1, LAG-3, TIM-3 and TIGIT were 79.3%, 78.8%, 62.7% and 69.5%, respectively.TIM-3 and TIGIT were expressed in 44.8% and 45.4% of tumor cells. The expression of TIM-3 in TILs was significantly correlated with the Ann-Arbor stage (P=0.039). There was a positive correlation Between PD-1 and LAG-3 or TIM-3 and TIGIT.In addition, LAG-3 expression in TILs was associated with inferior prognosis.Multivariate analysis showed that PS score and R-CHOP therapy were independent risk factors for OS and PFS in patients with DLBCL (P=0.000).

Conclusions

The expression level of TIM-3 is closely related to the Ann-Arbor stage, which may be expected to be a new index to evaluate the invasiveness of DLBCL. PD-1 was correlated with the expression of LAG-3, and the high expression of LAG-3 and LAG-3/PD-1 predicted the poor prognosis of DLBCL. Therefore, LAG-3 may become a new target of immunotherapy, or be used in combination with PD-1 inhibitors to improve the drug resistance of current patients with DLBCL.
Microscopic polyangiitis presenting with persistent cough and hemoptysis in pediatrics: A case report and review of the literature
Authors: Zhu Yantong , Zheng Xiangrong
Published: December 2022

Background

Microscopic polyangiitis (MPA) is a necrotizing vasculitis that involves small- and medium-sized vessels and is associated with the presence of antineutrophil cytoplasmic antibodies with a perinuclear staining pattern (p-ANCA). The kidney and lungs are the organs primarily affected. MPA is rare in children and is easily misdiagnosed. Below is a complete case history of the course of the disease.

Case presentation

An 11-year-old girl with a 1-month history of cough and hemoptysis showed no improvement after imipenem-cilastatin treatment. p-ANCA and microscopic hematuria and proteinuria were positive, and a chest CT revealed an area of shadow in the bilateral lower lobe of the lungs. Renal biopsies showed crescentic glomerulonephritis, and MPA was diagnosed based on these criteria. The patient exhibited dramatic clinical and imaging improvements after immunosuppressive treatment.

Conclusion

The organs most commonly involved in MPA in children are the lungs, kidneys, skin, nervous system organs, and organs of the gastrointestinal tract. Careful examination should be carried out in these patients while biopsies of the kidney or any other organs remain the gold standard for diagnostic purposes. Pulmonary involvement may be the initial symptom of the disease and should not be confused with pneumonia. A urinalysis should be performed in patients with hemoptysis. Antibiotics should be used with caution.
Social independence evaluation index for Japanese patients with childhood-onset chronic diseases
Authors: Inoue Yuzaburo , Umebayashi Hiroaki , Matsui Toshihiro , Nishiyama Susumu , Sakurai Ikuho , Maru Mitsue , Takeda Tetsuro , Tanigawa Koji , Miyamae Takako
Published: December 2022

Introduction

This study established an independent evaluation index for patients with childhood-onset chronic diseases in Japan.

Methods

From November to December 2020, three Delphi rounds were conducted. Thirty-nine participants completed at least one survey. We asked them about targets of social independence for 10 types of activities (education/labor/finance/acquisition of necessities/housing/transportation/leisure/social relationship/intimate relationships/sexuality). The Delphi technique was to be repeated until a consensus of over 80% of participants was reached.

Results

The targets chosen for measuring independence in patients with childhood-onset chronic diseases were as follows: “Graduation from high school,” “Labor for livelihood (including temporary turnover),” “Financially independent (including temporary turnover, excluding students),” “Buy or rent a house and buy the daily necessities and get the public services you need to live,” “Do housework alone,” “Plan alone and use transportation to get around,” “Participate in play/recreation/leisure activities on own initiative,” “Engage in relationships with other people outside of a limited environment (home, school, office, hospital, etc.),” “Create and maintain intimate or romantic relationships between individuals (couples, lovers, sexual partners),” and “Use or know how to use contraceptives and how to prevent sexually transmitted diseases.”

Conclusions

We established an independent evaluation index for patients with childhood-onset chronic diseases in Japan through a three-round Delphi process. The assessment of social independence using our independent evaluation index may help plan for and provide appropriate support and assistance to these patients.