bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Homozygous DNAJC3 Mutation Causes Monogenic Diabetes Mellitus Associated With Pancreatic Atrophy
Authors: Alwatban Saud , Alfaraidi Haifa , Alosaimi Abdulaziz , Alluhaydan Iram , Alfadhel Majid , Polak Michel , Almutair Angham
Published: June 2022

Introduction

DNAJC3, abundant in the pancreatic cells, attenuates endoplasmic reticulum stress. Homozygous DNAJC3 mutations have been reported to cause non-immune juvenile-onset diabetes, neurodegeneration, hearing loss, short stature, and hypothyroidism.

Case Description

We report a case of homozygous DNAJC3 mutation in two siblings of a consanguineous family. A 3-year-old boy presented with short stature and a thyroid nodule. Laboratory findings confirmed hypothyroidism. Subsequently, levothyroxine was administered. Growth hormone (GH) stimulation test results were within the normal limits. His stature was exceedingly short (80.5 cm) (−3.79 SDS). The patient developed sensorineural hearing loss at age 6 years; his intellectual functioning was impaired. Recombinant Human Growth Hormine (rhGH) treatment was postponed until the age of 6.9 years due to a strong family history of diabetes. At age 9 years, he developed an ataxic gait. Brain magnetic resonance imaging (MRI) revealed neurodegeneration. The patient developed diabetes at the age of 11 years—5 years after the initiation of rhGH treatment. Tests for markers of autoimmune diabetes were negative. Lifestyle modification was introduced, but insulin therapy was eventually required. Whole-exome-sequencing (WES) revealed a homozygous DNAJC3 mutation, which explained his clinical presentation. MRI revealed a small, atrophic pancreas. At the age of 17, his final adult height was 143 cm (−4.7 SDS). His elder brother, who had the same mutation, had a similar history, except that he had milder ataxia and normal brain MRI finding at the age of 28 years.

Conclusion

We propose that DNAJC3 mutation can be considered as a cause of maturity onset diabetes of the young. Patients with DNAJC3 mutations may possess a small atrophic pancreas.
Can Cervical Lymph Node Metastasis Increase the Risk of Distant Metastasis in Papillary Thyroid Carcinoma?
Authors: Wang Wenlong , Ding Ying , Jiang Wei , Li Xinying
Published: June 2022

Background

Distant metastasis (DM) is a rare event and has a negative effect on the prognosis for papillary thyroid carcinoma (PTC). The relationship between cervical lymph node metastasis and DM is complicated and unclear. This study aimed to evaluate the impact of N stage subclassification on different distant metastasis sites based on age stratification, especially for patients with papillary thyroid microcarcinoma.

Methods

A total of 28,712 patient with PTC cases between 2010 and 2018 were extracted from the Surveillance, Epidemiology, and End Results database. Multivariable logistic regression analysis was utilized to adjust for confounding variables. Risk stratification, including positive lymph node number and lymph node ratio, was established by receiver operating characteristic curves to help predict DM.

Results

Lung was the most common metastatic site regardless of N0, N1a disease, or N1b disease. As the N stage increased, the higher the rate of DM identified. After age stratification, only N1b disease significantly increased the risk of lung metastasis (LM; odds ratio, OR = 20.45, P < 0.001) rather than bone metastasis (BM; OR = 3.46, P > 0.05) in younger patients. However, in older patients, N1b disease significantly increased the risk of both LM (OR = 4.10, P < 0.001) and BM (OR = 2.65, P = 0.007). In patients with papillary thyroid microcarcinoma (PTMC), N1a disease did not increase the risk of DM, LM, and BM compared with N0 disease (P > 0.05). Furthermore, combined N stage with risk stratification has well performance in predicting DM (area under the curve, AUC = 0.761). Similar results were shown in PTC patients with LM (AUC = 0.770) and BM (AUC = 0.729).

Conclusion

Overall, the incidence of DM significantly increased with the progress of N disease after age stratification. N1a disease did not increase the risk of DM in PTMC patients, regardless of LM or BM. Combined N stage with risk stratification may be beneficial for DM prediction.
Mites as a Potential Path for Ce-Ti Exposure of Amphibians
Authors: Jacinto-Maldonado Mónica , Meza-Figueroa Diana , Pedroza-Montero Martín , Lesbarrères David , Robles-Morúa Agustín , Navarro-Espinoza Sofía , González-Grijalva Belem , Pérez-Segura Efrén , Silva-Campa Erika , Angulo-Molina Aracely , Paredes-León Ricardo
Published: June 2022

Despite the documented effects on human and animal health, particles smaller than 0.1 µm in diameter found in soils, sediments, and the atmosphere remain unregulated. Yet, cerium and titanium oxide nanoparticles associated with traffic increase mortality, cause behavioral changes, and inhibit the growth in amphibians. Mites of the genus Hannemania spend their early stages in the soil before becoming exclusive parasites of amphibians. Unlike other mites, Hannemania is found inside the epidermis of amphibians, thus facilitating the intake of particles, and leading to direct and chronic exposure. To better understand this exposure path, we sampled amphibians hosting mites in a river potentially polluted by traffic sources. Particles collected from mites were studied by scanning electron microscopy and Raman spectroscopy while sediment samples were analyzed for total metal content by portable X-ray fluorescence. Our results indicate that sediment samples showed significant correlations between elements (Zr, Mn, Ti, Nb, Fe) often associated with components in catalytic converters and a level of Zr that exceeded the local geochemical background, thus suggesting an anthropic origin. Furthermore, particles adhered to mites exhibited the characteristic Raman vibrational modes of ceria (CeO2, 465 cm−1), ceria-zirconia (CeO2-ZrO2, 149, 251, and 314 cm−1), and rutile (TiO2, 602 cm−1), pointing out to the deterioration of catalytic converters as the most likely source. This research highlights both the importance of unregulated catalytic converters as a source of ultrafine Ce-Ti particle pollution and the role of sub-cutaneous mites as a vector of these particles for amphibian exposure.
Occurrence and Risk Assessment of per- and Polyfluoroalkyl Substances in Water Source Protection Area of Southeastern China
Authors: He Shu , Ren Nanqi
Published: June 2022

In order to clarify the pollution characteristics and human health risks of PFASs pollutants in typical drinking water sources in Zhejiang Province, this study relies on ultra -performance liquid chromatography-mass spectrometry (UPLC-MS/MS) technology to analyze the pollution of 26 PFASs in 7 reservoirs in Zhejiang Province. The detected concentrations of PFASs were evaluated to further assess the human health risks. Total PFASs concentrations in the seven reservoirs ranged from 1.30 ng L−1–24.90 ng L−1. Among the 26 PFASs pollutants analyzed, PFOA and PFBA were the main PFASs pollutants, the detected concentrations of PFOA and PFBS ranging from 0.50 ng L−1–13.70 ng L−1 and 0 ng L−1–1.70 ng L−1, respectively. Then we evaluated 15 PFASs and calculated the results of the HQ value of the reproductive toxicity and hepatotoxicity of the total PFASs in this study ranged from 2.30 × 10–8 to 1.16 × 10–4 and 9 × 10–8 to 5.24 × 10–4 respectively, which were both lower than 0.01, indicating that there is no significant risk to the human body.
Microbial Remediation of Textile Dye Acid Orange by a Novel Bacterial Consortium SPB92
Authors: Bera Sweta Parimita , Shah Maulin P. , Godhaniya Manoj
Published: June 2022

Textile effluent generated during the dyeing process of textiles is a huge supplier to water toxicity all over the world. Textile dyes are the main toxic component found in the effluent sample which is difficult to treat. A bacterial consortium capable of decolourizing and degrading the textile dye acid orange is reported in this research article. The bacterial consortium was identified by 16 S rDNA sequence and phenotypic characteristics. It is composed of four strains i.e., Pseudomonas stutzeri (MW219251), Bacillus tequilensis (MW110471), Bacillus flexus (MW131645), Kocuria rosea (MW132411). The consortium was able to cause decolorization of azo dye acid orange (30 mg/L) in 23 h, when kept under static laboratory conditions. The optimal pH and temperature for color removal were pH 7.5 and 32°C, respectively. The decolorization of dye before and after was checked by UV-Visible absorption spectra. This gives evidence that decolorization was caused due to biodegradation. This was further assured by studying the reduction of biological oxygen demand (BOD5 (96%), chemical oxygen demand (COD) (79%), and TOC (total organic carbon) (54%) of the bacterial-treated water sample. The Fourier transform-infrared spectroscopy (FT-IR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS) results confirmed the mineralization of the dye. The results indicate the effectiveness of the bacterial consortium SPB92 in the biodegradation of acid orange dye. This demonstrates that the consortium has immense potential and will serve as an important contributor to the treatment of textile wastewater.
Dissecting Generalizability and Actionability of Disease-Associated Genes From 20 Worldwide Ethnolinguistic Cultural Groups
Authors: Chimusa Emile R. , Alosaimi Shatha , Bope Christian D.
Published: June 2022

Findings resulting from whole-genome sequencing (WGS) have markedly increased due to the massive evolvement of sequencing methods and have led to further investigations such as clinical actionability of genes, as documented by the American College of Medical Genetics and Genomics (ACMG). ACMG’s actionable genes (ACGs) may not necessarily be clinically actionable across all populations worldwide. It is critical to examine the actionability of these genes in different populations. Here, we have leveraged a combined WES from the African Genome Variation and 1000 Genomes Project to examine the generalizability of ACG and potential actionable genes from four diseases: high-burden malaria, TB, HIV/AIDS, and sickle cell disease. Our results suggest that ethnolinguistic cultural groups from Africa, particularly Bantu and Khoesan, have high genetic diversity, high proportion of derived alleles at low minor allele frequency (0.0–0.1), and the highest proportion of pathogenic variants within HIV, TB, malaria, and sickle cell diseases. In contrast, ethnolinguistic cultural groups from the non-Africa continent, including Latin American, Afro-related, and European-related groups, have a high proportion of pathogenic variants within ACG than most of the ethnolinguistic cultural groups from Africa. Overall, our results show high genetic diversity in the present actionable and known disease-associated genes of four African high-burden diseases, suggesting the limitation of transferability or generalizability of ACG. This supports the use of personalized medicine as beneficial to the worldwide population as well as actionable gene list recommendation to further foster equitable global healthcare. The results point out the bias in the knowledge about the frequency distribution of these phenotypes and genetic variants associated with some diseases, especially in African and African ancestry populations.
Body Composition and Metabolic Changes in a Lyon Hypertensive Congenic Rat and Identification of Ercc6l2 as a Positional Candidate Gene
Authors: Clark Karen C. , Wagner Valerie A. , Holl Katie L. , Reho John J. , Tutaj Monika , Smith Jennifer R. , Dwinell Melinda R. , Grobe Justin L. , Kwitek Anne E.
Published: June 2022

Central obesity is genetically complex, and its exponential increase in the last decades have made it a critical public health issue. The Lyon Hypertensive (LH) rat is a well-characterized hypertensive model that also exhibits spontaneous and profound differences in body weight and adiposity, relative to its metabolically healthy control, the Lyon Normotensive (LN) rat. The mechanisms underlying the body weight differences between these strains are not well-understood, thus a congenic model (LH17LNa) was developed where a portion of the proximal arm of LN chromosome 17 is introgressed on the LH genomic background to assess the contribution of LN alleles on obesity features. Male and female LH17LNa rats were studied, but male congenics did not significantly differ from LH in this study. Female LH17LNa rats exhibited decreases in total body growth, as well as major alterations to their body composition and adiposity. The LH17LNa female rats also showed decreases in metabolic rate, and a reduction in food intake. The increased adiposity in the female LH17LNa rats was specific to abdominal white adipose tissue, and this phenomenon was further explained by significant hypertrophy in those adipocytes, with no evidence of adipocyte hyperplasia. Sequencing of the parental strains identified a novel frameshift mutation in the candidate gene Ercc6l2, which is involved in transcription-coupled DNA repair, and is implicated in premature aging. The discovery of the significance of Ercc6l2 in the context of female-specific adipocyte biology could represent a novel role of DNA repair failure syndromes in obesity pathogenesis.
A Novel M7G-Related MicroRNAs Risk Signature Predicts the Prognosis and Tumor Microenvironment of Kidney Renal Clear Cell Carcinoma
Authors: Hong Peng , Du Huifang , Tong Ming , Cao Qingfei , Hu Ding , Ma Jiaji , Jin Yanyang , Li Zizhi , Huang Weichao , Tong Guangquan
Published: June 2022

Background: M7G modification is extremely vital for the development of many cancers, especially tumor immunity. M7G modification is a novel functional regulator of miRNA, and the researches on m7G-related miRNAs in kidney renal clear cell carcinoma (KIRC) are still insufficient. This research aims to establish a risk signature on the foundation of m7G-associated miRNAs, which can precisely forecast the prognosis of KIRC patients.

Methods: Transcriptome data and clinical data used in this study come from The Cancer Genome Atlas database. Our team utilized univariable Cox, Lasso and multivariable Cox analyses to construct a m7G-associated miRNAs risk signature that can forecast the prognosis of KIRC patients. Kaplan-Meier method, time-dependent receiver operating characteristic (ROC) curve, and the independent analysis of risk signatures were employed to verify the predictability and accuracy of the risk signature. Subsequently, based on CIBERSORT, ESTIMATE and ssGSEA algorithms, we speculated the potential impact of the proposed risk signature on tumor immune microenvironment. Ultimately, by virtue of the risk signature and tumor immunity, the hub genes affecting the prognosis of KIRC patients were screened out.

Results: Our team established and verified a prognostic signature comprising 7 m7G-associated miRNAs (miR-342-3p, miR-221-3p, miR-222-3p, miR-1277-3p, miR-6718-5p, miR-1251-5p, and miR-486-5p). The results of the Kaplan-Meier survival analysis revealed that the prognosis of KIRC sufferers in the high-risk group was often unsatisfactory. The accuracy of the prediction ability of the risk signature was verified by calculating the area under the ROC curve. Univariate-multivariate Cox analyses further showed that this risk signature could be utilized as an independent prognosis-related biomarker for KIRC sufferers. The results of the immune analysis revealed that remarkable diversities existed in immune status and tumor microenvironment between high-risk and low-risk groups. On the foundation of the proposed risk signature and other clinical factors, a nomogram was established to quantitatively forecast the survival of KIRC sufferers at 1, 3 and 5 years.

Conclusion: Based on m7G-related miRNAs, a risk signature was successfully constructed, which could precisely forecast the prognosis of sufferers and guide personalized immunotherapy for KIRC patients.
A Null Mutation of TNFRSF11A Causes Dysosteosclerosis, Not Osteopetrosis
Authors: Kırkgöz Tarık , Özkan Behzat , Hazan Filiz , Acar Sezer , Nalbantoğlu Özlem , Özkaya Beyhan , Kulalı Melike Ataseven , Gürsoy Semra , Ikegawa Shiro , Guo Long
Published: June 2022

Dysosteosclerosis (DOS) is a rare sclerosing bone dysplasia characterized by unique osteosclerosis of the long tubular bones and platyspondyly. DOS is inherited in an autosomal recessive manner and is genetically and clinically heterogeneous. To date, four individuals with DOS who have five different TNFRSF11A mutations have been reported. Based on their data, it is hypothesized that mutations producing aberrant mutant RANK proteins (missense or truncated or elongated) cause DOS, while null mutations lead to osteopetrosis, autosomal recessive 7 (OPTB7). Herein, we present the fifth case of TNFRSF11A-associated DOS with a novel homozygous frame-shift mutation (c.19_31del; p.[Arg7CysfsTer172]). The mutation is predicted to cause nonsense mutation-mediated mRNA decay (NMD) in all RANK isoform transcripts, resulting in totally null allele. Our findings suggest genotype-phenotype relationship in TNFRSF11A-associated OPTB7 and DOS remains unclear, and that the deficiency of TNFRSF11A functions might cause DOS, rather than osteopetrosis. More data are necessary to understand the phenotypic spectrum caused by TNFRSF11A mutations.
Contribution of Immunoglobulin Enhancers to B Cell Nuclear Organization
Authors: Bruzeau Charlotte , Cook-Moreau Jeanne , Pinaud Eric , Le Noir Sandrine
Published: June 2022

B cells undergo genetic rearrangements at immunoglobulin gene (Ig) loci during B cell maturation. First V(D)J recombination occurs during early B cell stages followed by class switch recombination (CSR) and somatic hypermutation (SHM) which occur during mature B cell stages. Given that RAG1/2 induces DNA double strand breaks (DSBs) during V(D)J recombination and AID (Activation-Induced Deaminase) leads to DNA modifications (mutations during SHM or DNA DSBs during CSR), it is mandatory that IgH rearrangements be tightly regulated to avoid any mutations or translocations within oncogenes. Ig loci contain various cis-regulatory elements that are involved in germline transcription, chromatin modifications or RAG/AID recruitment. Ig cis-regulatory elements are increasingly recognized as being involved in nuclear positioning, heterochromatin addressing and chromosome loop regulation. In this review, we examined multiple data showing the critical interest of studying Ig gene regulation at the whole nucleus scale. In this context, we highlighted the essential function of Ig gene regulatory elements that now have to be considered as nuclear organizers in B lymphocytes.
Aqueous Extract of Descuraniae Semen Attenuates Lipopolysaccharide-Induced Inflammation and Apoptosis by Regulating the Proteasomal Degradation and IRE1α-Dependent Unfolded Protein Response in A549 Cells
Authors: Hsieh Po-Chun , Peng Chung-Kan , Liu Guan-Ting , Kuo Chan-Yen , Tzeng I-Shiang , Wang Ming-Chieh , Lan Chou-Chin , Huang Kun-Lun
Published: June 2022

Background

Lipopolysaccharide (LPS)-induced acute lung injury (ALI) induces endoplasmic reticulum stress, unfolded protein response (UPR), apoptosis, and inflammation. Inositol-requiring enzyme 1 (IRE1)-α is important for adaptive and apoptotic UPR determination during ER stress. The aqueous extract of Descuraniae Semen (AEDS) is reported to be a safe and effective herb for the treatment of pulmonary edema as it shows anti-inflammatory activities.

Methods

We investigated the effects of AEDS on LPS-induced ALI in A549 cells with respect to the regulation of IRE1α-dependent UPR, proteasomal degradation, mitochondrial membrane potential (MtMP), inflammation, and apoptosis.

Results

AEDS attenuated ER stress by regulating the proteasomal degradation. LPS induced ER stress [binding immunoglobulin protein (BiP), phosphorylated IRE1α, sliced X-box binding protein 1 [XBP1s], phosphorylated cJUN NH2-terminal kinase (pJNK), B-cell lymphoma (Bcl)-2-associated X (Bax), Bcl-2], inflammation (nucleus factor-kappa B (NF-κB) p65 nuclear translocation, nucleus NF-κB, pro-inflammatory cytokines] and apoptosis [C/EBP homologous protein (CHOP), cytochrome c, caspase-8, and caspase-6, and TUNEL] were significantly attenuated by AEDS treatment in A549 cells. AEDS prevents LPS-induced decreased expression of MtMP in A549 cells.

Conclusions

AEDS attenuated LPS-induced inflammation and apoptosis by regulating proteasomal degradation, promoting IRE1α-dependent adaptive UPR, and inhibiting IRE1α-dependent apoptotic UPR. Moreover, IRE1α-dependent UPR plays a pivotal role in the mechanisms of LPS-induced ALI. Based on these findings, AEDS is suggested as a potential therapeutic option for treating patients with ALI.
Comprehensive Analysis and Summary of the Value of Immunophenotypes of Mature NK Cell Tumors for Differential Diagnosis, Treatment, and Prognosis
Authors: Pu Qiyao , Cao Xueyan , Liu Yuke , Yan Dongyao , Tan Ran , Li Jiwei , Yue Baohong
Published: June 2022

Background

Few studies have been performed to comprehensively analyze and summarize the immunophenotype and differential diagnosis of mature NK cell tumors, and there is often overlap between tumorigenic and reactive NK cell phenotypes. Furthermore, the impact of different phenotypes on patient prognosis has rarely been reported.

Methods

The degree of expression of extracellular and intracellular markers of NK cells in each group was compared by FCM, and the differences in expression of various markers among different disease groups and their impact on prognosis have been analyzed and summarized.

Results

Compared with normal NK cells, tumor cells of ANKL and ENKTL had characteristics of being more activated and progressive with larger FSC, in contrast to NK-CLPD and RNKL. Differential diagnoses with RNKL, ANKL, and ENKTL have broader FCM clues. In contrast, the phenotypes of NK-CLPD and RNKL are not significantly different, and consistent phenotypic abnormalities require ongoing monitoring to confirm malignant clones. The sensitivity of differentiating malignant NK cells from reactive NK cells by KIRs alone was poor. The clustering results showed that CD5, CD16, CD56, CD57, CD94, CD45RA, CD45RO, HLA-DR, KIRs, Granzyme B, Perforin and Ki-67 were differentially distributed in the expression of three NK cell tumors and reactive NK cell hyperplasia, so a comprehensive judgment using a wide range of antibody combinations is required in disease staging diagnosis. The tumor cell loads in BM and PB were also compared, and there was a clear correlation between the two. Moreover, the sensitivity of PB for monitoring tumor cells was up to 87.10%, suggesting that PB could be used as an alternative to BM for the diagnosis and screening of NK cell tumors. Analysis of the phenotypic impact of ENKTL patients on prognosis showed that those with CD7 and CD45RO expression had a poor prognosis, while those with positive KIRs had a better prognosis.

Conclusion

This study systematically characterized the FCM of mature NK cell tumors, emphasizing the importance and clinical value of accurate immunophenotyping in diagnosing, classifying, determining prognosis, and guiding treatment of the disease.
Different Responses of Chlorophyll a to the Passage of the Tropical Storm Wipha (2019) in the Coastal Waters of the Northern Beibu Gulf
Authors: Chen Ying , Ren Chaoxing , Feng Yuting , Shi Haiyi , Pan Gang , Cooper Mick , Zhao Hui
Published: June 2022

Tropical storms (TS) are important drivers of short-term changes and affects the coastal and marine environment. Based on in situ observational data from four locations in the coastal area of the northern Beibu Gulf and satellite data, we analyzed the changes in temperature, salinity, and turbidity during the transit of TS “Wipha” in 2019 and assessed the environmental factors controlling chlorophyll a concenteation (Chl-a) increases in the coastal area. Our results showed that in the coastal area, the growth of phytoplankton after the TS was mainly controlled by the nutrient and light availability. The increased input of freshwater by TS, including direct inputs from rainfall and increased river discharge, reduced the salinity. The decrease in salinity may indicate an increased input of nutrient-rich freshwater at all four stations (nutrients input: S1>S2>S3>S4). Nutrient concentration at S1, S2, and S3 implied by salinity was high, but that at S4 was limited. The shorter recovery time of turbidity after TS indicated the faster improvement of light conditions in this area [recovery time: S4 (2 days)< S1 (3 days)< S3 (5 days)< S2 (10 days)]. The high turbidity associated with poor light penetration was an important factor limiting phytoplankton growth at station 2, with a slow recovery of the turbidity to pre-TS levels. The rapid recovery of the turbidity to the pre-TS levels at S1, S3, and S4 suggested good light conditions soon after the TS, and probably led to a significant increase in Chl-a after the TS ([Chl-a]: S1>S3>S4). The less of an increase of Chl-a at S4 was not only related to nutrient restriction but also related to weak mixing of the water column, while the least significant decrease in the SST at S4 implied that the enhancing mixing after TS was limited.
Cannabinoids, Medical Cannabis, and Colorectal Cancer Immunotherapy
Authors: Zaiachuk Mariia , Pryimak Nazar , Kovalchuk Olga , Kovalchuk Igor
Published: June 2022

Colorectal cancer is a major public health problem. Unfortunately, currently, no effective curative option exists for this type of malignancy. The most promising cancer treatment nowadays is immunotherapy which is also called biological or targeted therapy. This type of therapy boosts the patient's immune system ability to fight the malignant tumor. However, cancer cells may become resistant to immunotherapy and escape immune surveillance by obtaining genetic alterations. Therefore, new treatment strategies are required. In the recent decade, several reports suggest the effectiveness of cannabinoids and Cannabis sativa extracts for inhibiting cancer proliferation in vitro and in vivo, including intestinal malignancies. Cannabinoids were shown to modulate the pathways involved in cell proliferation, angiogenesis, programmed cell death and metastasis. Because of that, they are proposed as adjunct therapy for many malignancies. By far less information exists on the potential of the use of cannabis in combination with immunotherapy. Here, we explore the possibility of the use of cannabinoids for modulation of immunotherapy of colon cancer and discuss possible advantages and limitations.
Case Report: A Case Series of Immunobiological Therapy (Anti-TNF-α) for Patients With Erythema Nodosum Leprosum
Authors: Mendes Ana Flávia Moura , Gomes Ciro Martins , Kurizky Patrícia Shu , Ianhez Mayra
Published: June 2022

Patients with leprosy may experience a chronic and severe type II leprosy reaction (ENL) erythema nodosum leprosum that may not respond to thalidomide and systemic immunosuppressants or may even cause serious adverse events. We here present four patients in whom anti-TNF-α therapy was used with successful results and compare our findings with other published cases. Four patients with chronic and severe ENL who did not respond to, at least, thalidomide and steroids (high doses) were followed up at two reference centers in Brazil. A thorough laboratory investigation was performed to exclude tuberculosis and other diseases before the start of immunobiological medication. Three patients were started on etanercept, and one patient was started on adalimumab. Of all patients, three developed severe adverse events resulting from the use of classical immunosuppressants for ENL (cataracts, deep vein thrombosis, diabetes, and osteoporosis). In all cases, a reduction in the number of ENL and, at least half of the immunosuppressant dose between 6 months and 2 years, were observed. Long-term follow-up of one patient revealed a dramatic reduction in hospital admissions due to ENL, from 12 instances in 1 year (before biologic therapy) to none (after biologic therapy), along with an improvement in condyloma acuminatum. In addition, no direct adverse events were observed with biologics. Treatment with anti-TNF-α therapy may be used as an alternative in patients with chronic and severe ENL who do not respond to traditional treatment (e.g., thalidomide, steroids, and other immunosuppressants). This treatment can help reduce the frequency of ENL, the immunosuppressive burden, and the number of hospital admissions.
How to Safeguard University Students Against HIV Transmission? Results of a Cross-Sectional Study in Southern Italy
Authors: Licata Francesca , Angelillo Silvia , Oliverio Antonella , Di Gennaro Gianfranco , Bianco Aida
Published: June 2022

Introduction

Young people represent a growing share of the group living with HIV, and monitoring the sexual behaviors of this vulnerable age group is necessary to control and prevent the HIV/AIDS pandemic. The present study has been conducted to investigate the level of knowledge and attitudes toward HIV infection and sexual behaviors among a sample of undergraduate university students in Southern Italy.

Methods

Data were collected through an anonymous online questionnaire between 1st to 31st July 2020 and included questions on socio-demographic and sexual history characteristics, knowledge and attitudes toward HIV infection, sexual behaviors, and sources of information about HIV. The eligibility criteria for the study were: age between 18 and 30 years and registered as an undergraduate student at the university.

Results

Among the 1,318 students who completed the survey, 62.5% knew that HIV can be transmitted through blood, vaginal secretions and semen. The overall median knowledge score was 10, and the main determinants of knowledge were being younger and attending to medical or life science majors. Less than half of the students (45.8%) reported that they always wear a condom during any sexual activity. Predictors of consistent condom use were being younger, having a later sexual debut and a good knowledge score.

Conclusions

The study findings showed a not completely satisfactory level of knowledge and unsafe sex practices among university students. These results reiterate the need to tailor HIV prevention strategies among young individuals. Such a change could dispel misconceptions about HIV transmission and prevention that affect risk-taking sexual behaviors. These strategies may ultimately contribute to lessing the effect of HIV/AIDS transmission in Italy.
Humoral Response to mRNA-1273 SARS-CoV-2 Vaccine in Peritoneal Dialysis Patients: Is Boostering After Six Months Adequate?
Authors: Beilhack Georg , Monteforte Rossella , Frommlet Florian , Reindl-Schwaighofer Roman , Strassl Robert , Vychytil Andreas
Published: June 2022

In dialysis patients the humoral response to anti-SARS-CoV-2 vaccines is attenuated and rapidly declines over time. However, data on the persistence of the immune response in peritoneal dialysis (PD) patients are scarce, particularly after a third (booster) dose with mRNA-1273 vaccine. In this prospective cohort study, we report anti-SARS-CoV-2 antibody levels in PD patients before and after the third dose of mRNA-1273 vaccine. Six months after the second dose, anti-SARS-CoV-2 antibodies were detected in all patients (n = 34). However, within this time period antibodies substantially declined in 31 of 34 patients (4.5-fold, median = 192 BAU/mL, p = 1.27 × 10–9) and increased in three patients. In accordance with government regulations, a third dose of mRNA-1273 vaccine (50 μg) was given to 27 PD patients 6 months after the second dose which induced a significant increase of anti-SARS-CoV-2 antibody titers (58.6-fold, median = 19405 BAU/mL, p = 1.24 × 10–29). A mixed model analysis showed that a lower Davies Comorbidity Score and a higher GFR were associated with higher antibody titers (p = 0.03 and p = 0.02). The most common adverse events after the third dose were pain at the injection site (77.8%) and fatigue (51.9%). No hospitalizations were reported. In conclusion, 6 months after the second dose of mRNA-1273 vaccine, anti-SARS-CoV-2 antibodies substantially decreased in PD patients, whereas a well-tolerated third dose induced a robust humoral response. Our data suggest that the administration of a booster dose within a shorter interval than 6 months should be considered in PD patients in order to maintain high anti-SARS-CoV-2 antibody levels and assure protection from severe COVID-19 disease.
Variations in Soil Nutrient Dynamics and Bacterial Communities After the Conversion of Forests to Long-Term Tea Monoculture Systems
Authors: Gui Heng , Fan Lichao , Wang Donghui , Yan Peng , Li Xin , Pang Yinghua , Zhang Liping , Zamanian Kazem , Shi Lingling , Xu Jianchu , Han Wenyan
Published: June 2022

The soil microbial community is a key indicator to evaluate the soil health and productivities in agricultural ecosystems. Monoculture and conversions of forests to tea plantations have been widely applied in tea plantation globally, but long-term monoculture of tea plantation could lead to soil degradation and yield decline. Understanding how long-term monoculture systems influence the soil health and ecosystem functions in tea plantation is of great importance for soil environment management. In this study, through the comparison of three independent tea plantations across eastern China composed of varying stand ages (from 3 to 90 years after conversion from forest), we found that long-term tea monoculture led to significant increases in soil total organic carbon (TOC) and microbial nitrogen (MBN). Additionally, the structure, function, and co-occurrence network of soil bacterial communities were investigated by pyrosequencing 16S rRNA genes. The pyrosequencing analysis revealed that the structures and functions of soil bacterial communities were significantly affected by different stand ages, but sampling sites and land-use conversion (from forest to tea plantation) had stronger effects than stand age on the diversity and structure of soil bacterial communities. Soil bacterial diversity can be improved with increasing stand ages in tea plantation. Further RDA analysis revealed that the C and N availability improvement in tea plantation soils led to the variation of structure and function in soil bacterial communities. Moreover, co-occurrence network analysis of soil bacterial communities also demonstrated that interactions among soil bacteria taxa were strengthened with increasing stand age. Our findings suggest that long-term monoculture with proper managements could be beneficial to soil ecosystems by increasing the C and N content and strengthening bacterial associations in tea plantations. Overall, this study provides a comprehensive understanding of the impact of land-use change and long-term monoculture stand age on soil environments in tea plantation.
Proteolysis at the Archaeal Membrane: Advances on the Biological Function and Natural Targets of Membrane-Localized Proteases in Haloferax volcanii
Authors: De Castro Rosana E. , Giménez María I. , Cerletti Micaela , Paggi Roberto A. , Costa Mariana I.
Published: June 2022

Proteolysis plays a fundamental role in many processes that occur within the cellular membrane including protein quality control, protein export, cell signaling, biogenesis of the cell envelope among others. Archaea are a distinct and physiologically diverse group of prokaryotes found in all kinds of habitats, from the human and plant microbiomes to those with extreme salt concentration, pH and/or temperatures. Thus, these organisms provide an excellent opportunity to extend our current understanding on the biological functions that proteases exert in cell physiology including the adaptation to hostile environments. This revision describes the advances that were made on archaeal membrane proteases with regard to their biological function and potential natural targets focusing on the model haloarchaeon Haloferax volcanii.
TRPs in Ovarian Serous Cystadenocarcinoma: The Expression Patterns, Prognostic Roles, and Potential Therapeutic Targets
Authors: Zhang Cheng , Xu Cong , Ma Chuanshun , Zhang Qinghua , Bu Siyuan , Zhang Dao-Lai , Yu Liting , Wang Hongmei
Published: June 2022

Ovarian cancer (usually ovarian serous cystadenocarcinoma, or OV) is the fifth leading cause of cancer-related deaths in women, with more than 184,000 deaths reported worldwide annually, and is a highly malignant carcinoma. However, the mechanism of etiology remains unclear. The lack of prognostic and diagnostic biomarkers is a main limitation for clinical diagnosis and treatment. The transient receptor potential (TRP) channels play essential roles in the occurrence and development of cancers which may have the potential as a therapeutic target for OV. In our study, we used bioinformatic methods to study the potential effect and function of the TRP family in patients with OV. Differential expression analysis showed that the expression of TRPC7, TRPV4, and other TRP family members was significantly different between tumor and normal tissues. Through survival analysis, we screened out that the high expression of TRPC7, TRPV4, and TRPM (2,4,8) was negatively correlated with the prognosis of patients. In contrast, the low expression of TRPM3 was negatively associated with the prognosis. Cox regression analysis further indicated that TRPV4 was OV’s most likely therapeutic target. Finally, we conducted mRNA expression analysis, functional enrichment analysis, and immune infiltration analysis to confirm that TRPV4 was the most convincing therapeutic target of OV.
Functional Connectivity Dynamics Altered of the Resting Brain in Subjective Cognitive Decline
Authors: Wei Yi-Chia , Kung Yi-Chia , Huang Wen-Yi , Lin Chemin , Chen Yao-Liang , Chen Chih-Ken , Shyu Yu-Chiau , Lin Ching-Po
Published: June 2022

Background

Subjective cognitive decline (SCD) appears in the preclinical stage of the Alzheimer's disease continuum. In this stage, dynamic features are more sensitive than static features to reflect early subtle changes in functional brain connectivity. Therefore, we studied local and extended dynamic connectivity of the resting brain of people with SCD to determine their intrinsic brain changes.

Methods

We enrolled cognitively normal older adults from the communities and divided them into SCD and normal control (NC) groups. We used mean dynamic amplitude of low-frequency fluctuation (mdALFF) to evaluate region of interest (ROI)-wise local dynamic connectivity of resting-state functional MRI. The dynamic functional connectivity (dFC) between ROIs was tested by whole-brain-based statistics.

Results

When comparing SCD (N = 40) with NC (N = 45), mdALFFmean decreased at right inferior parietal lobule (IPL) of the frontoparietal network (FPN). Still, it increased at the right middle temporal gyrus (MTG) of the ventral attention network (VAN) and right calcarine of the visual network (VIS). Also, the mdALFFvar (variance) increased at the left superior temporal gyrus of AUD, right MTG of VAN, right globus pallidum of the cingulo-opercular network (CON), and right lingual gyrus of VIS. Furthermore, mdALFFmean at right IPL of FPN are correlated negatively with subjective complaints and positively with objective cognitive performance. In the dFC seeded from the ROIs with local mdALFF group differences, SCD showed a generally lower dFCmean and higher dFCvar (variance) to other regions of the brain. These weakened and unstable functional connectivity appeared among FPN, CON, the default mode network, and the salience network, the large-scale networks of the triple network model for organizing neural resource allocations.

Conclusion

The local dynamic connectivity of SCD decreased in brain regions of cognitive executive control. Meanwhile, compensatory visual efforts and bottom-up attention rose. Mixed decrease and compensatory increase of dynamics of intrinsic brain activity suggest the transitional nature of SCD. The FPN local dynamics balance subjective and objective cognition and maintain cognitive preservation in preclinical dementia. Aberrant triple network model features the dFC alternations of SCD. Finally, the right lateralization phenomenon emerged early in the dementia continuum and affected local dynamic connectivity.
Most Pathways Can Be Related to the Pathogenesis of Alzheimer’s Disease
Authors: Morgan Sarah L. , Naderi Pourya , Koler Katjuša , Pita-Juarez Yered , Prokopenko Dmitry , Vlachos Ioannis S. , Tanzi Rudolph E. , Bertram Lars , Hide Winston A.
Published: June 2022

Alzheimer’s disease (AD) is a complex neurodegenerative disorder. The relative contribution of the numerous underlying functional mechanisms is poorly understood. To comprehensively understand the context and distribution of pathways that contribute to AD, we performed text-mining to generate an exhaustive, systematic assessment of the breadth and diversity of biological pathways within a corpus of 206,324 dementia publication abstracts. A total of 91% (325/335) of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways have publications containing an association via at least 5 studies, while 63% of pathway terms have at least 50 studies providing a clear association with AD. Despite major technological advances, the same set of top-ranked pathways have been consistently related to AD for 30 years, including AD, immune system, metabolic pathways, cholinergic synapse, long-term depression, proteasome, diabetes, cancer, and chemokine signaling. AD pathways studied appear biased: animal model and human subject studies prioritize different AD pathways. Surprisingly, human genetic discoveries and drug targeting are not enriched in the most frequently studied pathways. Our findings suggest that not only is this disorder incredibly complex, but that its functional reach is also nearly global. As a consequence of our study, research results can now be assessed in the context of the wider AD literature, supporting the design of drug therapies that target a broader range of mechanisms. The results of this study can be explored at www.adpathways.org.
The Pathological Mechanism Between the Intestine and Brain in the Early Stage of Parkinson's Disease
Authors: Yang Runing , Gao Ge , Yang Hui
Published: June 2022

Parkinson's disease (PD) is the second most common chronic progressive neurodegenerative disease. The main pathological features are progressive degeneration of neurons and abnormal accumulation of α-synuclein. At present, the pathogenesis of PD is not completely clear, and many changes in the intestinal tract may be the early pathogenic factors of PD. These changes affect the central nervous system (CNS) through both nervous and humoral pathways. α-Synuclein deposited in the intestinal nerve migrates upward along the vagus nerve to the brain. Inflammation and immune regulation mediated by intestinal immune cells may be involved, affecting the CNS through local blood circulation. In addition, microorganisms and their metabolites may also affect the progression of PD. Therefore, paying attention to the multiple changes in the intestinal tract may provide new insight for the early diagnosis and treatment of PD.
Plcg2M28L Interacts With High Fat/High Sugar Diet to Accelerate Alzheimer’s Disease-Relevant Phenotypes in Mice
Authors: Oblak Adrian L. , Kotredes Kevin P. , Pandey Ravi S. , Reagan Alaina M. , Ingraham Cynthia , Perkins Bridget , Lloyd Christopher , Baker Deborah , Lin Peter B. , Soni Disha M. , Tsai Andy P. , Persohn Scott A. , Bedwell Amanda A. , Eldridge Kierra , Speedy Rachael , Meyer Jill A. , Peters Johnathan S. , Figueiredo Lucas L. , Sasner Michael , Territo Paul R. , Sukoff Rizzo Stacey J. , Carter Gregory W. , Lamb Bruce T. , Howell Gareth R.
Published: June 2022

Obesity is recognized as a significant risk factor for Alzheimer’s disease (AD). Studies have supported the notion that obesity accelerates AD-related pathophysiology in mouse models of AD. The majority of studies, to date, have focused on the use of early-onset AD models. Here, we evaluate the impact of genetic risk factors on late-onset AD (LOAD) in mice fed with a high fat/high sugar diet (HFD). We focused on three mouse models created through the IU/JAX/PITT MODEL-AD Center. These included a combined risk model with APOE4 and a variant in triggering receptor expressed on myeloid cells 2 (Trem2R47H). We have termed this model, LOAD1. Additional variants including the M28L variant in phospholipase C Gamma 2 (Plcg2M28L) and the 677C > T variant in methylenetetrahydrofolate reductase (Mthfr677C >T) were engineered by CRISPR onto LOAD1 to generate LOAD1.Plcg2M28L and LOAD1.Mthfr677C >T. At 2 months of age, animals were placed on an HFD that induces obesity or a control diet (CD), until 12 months of age. Throughout the study, blood was collected to assess the levels of cholesterol and glucose. Positron emission tomography/computed tomography (PET/CT) was completed prior to sacrifice to image for glucose utilization and brain perfusion. After the completion of the study, blood and brains were collected for analysis. As expected, animals fed a HFD, showed a significant increase in body weight compared to those fed a CD. Glucose increased as a function of HFD in females only with cholesterol increasing in both sexes. Interestingly, LOAD1.Plcg2M28L demonstrated an increase in microglia density and alterations in regional brain glucose and perfusion on HFD. These changes were not observed in LOAD1 or LOAD1.Mthfr677C >T animals fed with HFD. Furthermore, LOAD1.Plcg2M28L but not LOAD1.Mthfr677C >T or LOAD1 animals showed transcriptomics correlations with human AD modules. Our results show that HFD affects the brain in a genotype-specific manner. Further insight into this process may have significant implications for the development of lifestyle interventions for the treatment of AD.
The Association Between Glymphatic System Dysfunction and Cognitive Impairment in Cerebral Small Vessel Disease
Authors: Tang Jie , Zhang Miaoyi , Liu Na , Xue Yang , Ren Xue , Huang Qi , Shi Langfeng , Fu Jianhui
Published: June 2022

The mechanism of cognitive impairment in patients with cerebral small vessel disease (CSVD) remains unknown. The glymphatic system dysfunction, which has been demonstrated to influence cognitive impairment, can be evaluated by diffusion tensor image analysis along the perivascular space (ALPS index). We explored whether cognitive impairment in CSVD is associated with glymphatic clearance dysfunction. In this study, 133 patients with CSVD were enrolled and underwent neuropsychological test batteries as well as magnetic resonance imaging (MRI). They were then categorized into a CSVD with cognitive impairment (CSVD-CI) group and a cognitively normal CSVD (CSVD-CN) group. The ALPS index and four CSVD markers [white matter lesions (WMLs), cerebral microbleeds (CMBs), lacunes, and perivascular spaces (PVSs)] were also assessed. Univariate analysis showed that the ALPS index was significantly different between the CSVD-CN (n = 50) and CSVD-CI groups (n = 83) (p < 0.001). This difference remained significant (95% CI < 0.001–0.133) after adjusting for six common risk factors (age, education, hypertension, diabetes, smoking, and alcohol abuse) as well as CSVD markers. The ALPS index was independently linearly correlated with global cognitive function, executive function, attention function, and memory after adjusting for the aforementioned six risk factors or CSVD markers. Our results suggest that glymphatic system impairment is independently related to cognitive impairment in patients with CSVD.