bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation strategies of mutualistic rhizobacteria on Arabidopsis roots
Authors:   , Zhang Hao
Published: June 2023

Beneficial plant root-associated microorganisms carry out a range of functions that are essential for plant performance. To study bacterial adaptation in the rhizosphere, we employed experimental evolution to track the physiological and genetic dynamics of root-dwelling Pseudomonas protegens in the Arabidopsis thaliana rhizosphere under axenic conditions. We identified 35 mutations in 28 genes, including those important for cell surface decoration. Four mutations in three OBC3 (O-antigenic polysaccharide biosynthesis cluster 3) genes, i.e., oafA, galE and RS09880, were identified that can be associated with the decoration of the O-antigen, a major constituent of lipopolysaccharide (LPS). Enhanced root colonization of oafA and RS09880 mutants is linked to enhanced root attachment in a plant. OafA encodes a two-domain O-antigen acetyltransferase, and the mutations introduce a premature stop codon halfway directly between both domains. Intriguingly, we observed similar mutations in OBC3 of publicly available environmental P. protegens strain genomes, including several non-plant associated ones. Two OBC3 mutants, i.e., in galE and RS09880, showed altered LPS structure and reduced sensitivity towards the environmental phage ΦGP100. Altogether, our results highlight a role for O-antigen decoration in root colonization, likely by impacting bacterial root attachment, and reveal OBC3 mutations in nature, which occasionally can contribute to resistance to environmental phages.
Expression of serotonin receptors in mouse oocytes and preimplantation embryos
Authors: Veselá J , Rehák P , Mihalik J , Czikková S , Pokorný J , Koppel J
Published: June 2023

Serotonin receptors have been found in several reproductive organs as well as in the central nervous system. Serotonin-binding sites have been demonstrated in duck ovarian follicles and the testis, hamster ovaries, human granulosa cells and mouse placenta. Local production of serotonin by the rat ovary, oviduct, uterus and testis has also been reported. We analyzed the expression of three types of serotonin receptors: 5-HT1B, 5-HT2C and 5-HT1D by reverse transcription-polymerase chain reaction in mouse unfertilized oocytes and preimplantation embryos from zygotes to the blastocyst stage in vivo. Transcripts for 5-HT1B and 5-HT2C serotonin receptors were detected neither in unfertilized oocytes nor at any stages of in vivo developing preimplantation embryos. Serotonin 5-HT1D receptor mRNA was present in unfertilized oocytes, zygotes, 2-cell embryos, compacted morulae and in vivo produced expanded blatocysts. The expression of the mRNA 5-HT1D serotonin receptor was also detected in blastocysts cultured in vitro. When added to the culture medium, specific serotonin 5-HT1D agonist sumatriptan (1 μM) significantly inhibited the development of mouse embryos cultured in vitro. Demonstration of the expression of 5-HT1D serotonin receptor in mouse oocytes and preimplantation embryos supports the idea of a functional serotonin (5-HT1D) receptor in early mammalian development.
Elevated Opioid Growth Factor Alters the Limbus in Type 1 Diabetic Rats
Authors: McLaughlin Patricia J. , Sassani Joseph W. , Diaz David , Zagon Ian S.
Published: June 2023

Ocular surface complications occur in more than 50% of individuals diagnosed with diabetes. The financial and health-related burden of diabetes is increasing annually. Several major ocular complications associated with diabetes involve the limbus. The vascular limbus, adjacent to the avascular cornea, is the source of circulating growth factors, elevated glucose, and cytokines for the cornea. The Opioid Growth Factor (OGF) - Opioid OGF Receptor (OGFr) axis is comprised of its effector peptide, OGF, [Met5]-enkephalin and the nuclear-associated receptor, OGFr, and has been demonstrated to be dysfunctional in diabetes with elevated serum and tissue levels of the inhibitory growth factor OGF recorded in corneal tissue. Little is known regarding the impact of OGF-OGFr axis dysregulation in diabetes on the functioning of the limbus constituents in support of corneal homeostasis. Adult male and female Sprague-Dawley rats were rendered hyperglycemic through intraperitoneal injections of streptozotocin (T1D); a subset of T1D rats received topical naltrexone (NTX) applied to the cornea and limbus daily for 8 weeks. At 4 and/or 8 weeks of hyperglycemia, different cohorts of animals were euthanized, eyes removed and processed for assessment of limbal morphology, expression of OGF, OGFr, cytokeratin 15, a marker for limbal cells, and Ki-67, a marker of proliferation. Limbal epithelial morphology (cell diameter, packing density) was altered in T1D male and female rats. OGF and OGFr were overexpressed in the limbus and CK15 expression was decreased, relative to normal control rats of the same sex. Blockade of the OGF- OGFr axis with NTX reversed limbal epithelial cell defects, and reduced OGF limbal tissue levels to those recorded in non-diabetic rats. In summary, OGF-OGFr axis dysregulation was observed in the limbus of T1D rats, contributing to the altered limbal morphology and delayed corneal surface healing observed in diabetic animals.
A reestruturação curricular do ensino médio do Rio Grande do Sul: perspectivas e desafios
Authors: Delanogari Franciele Noro , Leite Fabiane De Andrade
Published: June 2023

O estudo acerca da reestruturação curricular do ensino médio no estado do Rio Grande do Sul iniciado em 2012 é o tema deste texto, o qual busca analisar as compreensões dos professores acerca dos seus papéis no processo de implantação e na realização da proposta. Para tanto, a escrita trata-se de uma pesquisa de cunho qualitativo que teve como instrumento a realização de um questionário semiestruturado aos professores da rede estadual de ensino. Ademais, constataram-se desafios e possibilidades para a inserção de novas polí­ticas curriculares nos sistemas de ensino e destacam-se o desenvolvimento da autonomia docente no processo, bem como o reconhecimento da importância de uma nova perspectiva de aprendizagem dos alunos a partir da pesquisa.
Escritas reflexivas compartilhadas como estratégia de formação inicial: a pesquisa no ensino e na iniciação à docência em ciências
Authors: Weyh Dattein Raquel , Da Costa GÃ¼llich Roque Ismael , Basso Zanon Lenir
Published: June 2023

O texto apresenta a discussão da temática da iniciação à docência em Ciências e Biologia, em relação ao subprojeto do PIBID Ciências e aos indí­cios de constituição docente pela via das narrativas de formação que são tematizadas pelo viés da pesquisa na formação e docência, sendo este um recorte de uma dissertação de mestrado. Busca também compreender e abordar, por meio da perspectiva histórico-cultural e de reflexões crí­ticas, as dimensões da iniciação à docência registradas em 13 Diários de Bordo (DB), produzidos por 13 bolsistas do PIBID Ciências, incluindo a autora da dissertação, quatro supervisoras e o professor formador do subprojeto, totalizando o envolvimento de 18 sujeitos de pesquisa. As narrativas foram analisadas por meio de pesquisa qualitativa com o objetivo de identificar escritas reflexivas compartilhadas (ERC) no contexto formativo vivenciado no PIBID Ciências, sendo este organizado com base na Investigação-Ação (IA) com enfoque crí­tico e emancipatório. A organização metodológica, baseada na Análise Textual Discursiva (ATD) das narrativas dos DB, possibilitou o diagnóstico de discursos de cunho descritivo e interpretativo, possibilitando a percepção de três tematizações que perpassaram o processo formativo: experimentação no ensino e na docência; o livro didático no ensino de Ciências; a pesquisa no ensino e na iniciação à docência em Ciências, sendo esta última abordada com ênfase neste artigo. A partir das narrativas que originaram as temáticas, tem-se a constatação de um processo formativo transformado por leituras e discussões de teóricos da educação, cujos licenciandos avançam de escritas descritivas e com conhecimentos do cotidiano para escritas valorativas e com conhecimentos cientí­ficos. Assim, encontramos indí­cios de interações constitutivas dos sujeitos de pesquisa e ação que demonstram um processo permeado por conhecimentos (teóricos e práticos, cientí­ficos e cotidianos) imbricadas nas ERC e colaborativas nos DB.
Ensino & aprendizagem na cibercultura: alcances e dilemas na formação docente
Authors: De Barros Patrícia Marcondes
Published: June 2023

O presente artigo tem como objetivo geral analisar o processo de ensino e aprendizagem no contexto da cibercultura, formadora de uma nova subjetividade coadunada a pós-modernidade, expressa pela juventude contemporânea. A juventude atrelada à cultura digital apresenta expectativas e saberes diferenciados das gerações anteriores em relação ao processo educacional. Para a realização do presente estudo, de cunho qualitativo, serão estabelecidas interlocuções com a psicologia, a comunicação, a sociologia e a história, a exemplo, perscrutando as novas relações educacionais frente ao horizonte de possibilidades do devir. Tratamos aqui, de repensar o processo ensino-aprendizagem sob a égide das mudanças paradigmáticas postuladas pela cibercultura, conferindo novos sentidos, reconfigurando espaços e, também, reagindo à liquidez da pós-modernidade em prol de uma educação não apenas consonante às tecnologias, mas também humanista e aberta à complexidade e diversidade dos “meios e mensagens” que a contemporaneidade nos traz.
Transabdominal ultrasound for complicated diverticular disease
Authors: Semionkin E. I. , Khubezov D. A. , Lucanin R. V. , Puchkov D. K. , Ogoreltzev A. Yu. , Yudina E. A. , Bragina I. Yu. , Gordeeva A. S.
Published: June 2023

AIM: to evaluate the effectiveness of transabdominal ultrasound for complicated diverticular disease (CDD).

PATIENTS AND METHODS: a retrospective study included 108 patients with CDD. All patients had left-sided diverticula, while in the vast majority of patients, diverticula were located in the sigmoid colon.

RESULTS: transabdominal ultrasound was informative in 84.3% of patients; in 74.1% of cases (80 patients), diverticula were clearly identified with sizing, infiltration of the intestinal wall, fluid around the intestine, the presence of a fistulous tract in perforation, gas collections; 11 (10.2%) patients had indirect signs, such as diffuse hypoechogenic thickening of the intestinal wall, its infiltration, fistulous tract, liquid near the intestine, hyperechogenic structure of fat near the intestine, the presence of a paracolic abscess, absence or slowing down of peristalsis; 17 (15.7%) patients showed no changes, one had a false positive conclusion.

CONCLUSION: transabdominal ultrasound is an informative and non-invasive method for diagnosing complicated diverticular disease in urgent surgery.
Late outcomes of parastomal hernia repair
Authors: Malgina N. V. , Rodoman G. V. , Dolgina T. U.
Published: June 2023

AIM: to assess late results of parastomal hernia repair using Sugarbaker’s technique modifications.

PATIENTS AND METHODS: prospective non-randomised study included 60 patients with parastomal hernia, which underwent surgery in 2013-2019. Patients were divided in two groups. The control group included 30 patients with “classic” Sugabacker method, the main group included 30 patients with Sugarbaker’s procedure added by suture of abdominal wall defect. Both groups were homogenous by age, gender, hernia size, type of primal disease and preoperative quality of life (EQ-5D-5L). The efficacy of the treatment was estimated by recurrence rate and quality of life 1 and 2 years after surgery.

RESULTS: the recurrence rate in the main group was significantly lower after 1 and 2 years (3 vs 13; p = 0.01). Quality of life in the main group was significantly higher after the first year of follow-up (the median of the weighted coefficient 0.92 vs 0.89; p = 0.04) and this trend has preserved 2 years after surgery.

CONCLUSION: suture of abdominal wall defect in Sugarbaker’s procedure for parastomal hernia reduces recurrence rate significantly and provides better quality of life.
Radiated tumor cell-derived microparticles effectively kill stem-like tumor cells by increasing reactive oxygen species
Authors: Hu Yan , Wan Chao , Yang Xiao , Tian Yu , Deng Suke , An Dandan , Wang Yijun , Wang Jiacheng , Liao Zhiyun , Meng Jingshu , Qin You , Sun Yajie , Yang Kunyu
Published: June 2023

Stem-like tumor cells (SLTCs) are thought to be the cellular entity responsible for clinical recurrence and subsequent metastasis. Inhibiting or killing SLTCs can effectively reduce recurrence and metastasis, yet little has been done to clear SLTCs because they are usually resistant to chemotherapy, radiotherapy, and even immunotherapy. In this study, we established SLTCs by low-serum culture and confirmed that the low-serum-cultured tumor cells were in a quiescent state and resistant to chemotherapy, showing features of SLTCs, consistent with the reported data. We demonstrated that SLTCs had high levels of reactive oxygen species (ROS). Based on the finding that radiated tumor cell-derived microparticles (RT-MPs) contained ROS, we used RT-MPs to kill SLTCs. We found that RT-MPs could further increase ROS levels and kill SLTCs in vivo and in vitro partially by ROS carried by the RT-MPs themselves, providing a new method for eliminating SLTCs.
Gut microbial dysbiosis in patients with Cushing’s disease in long-term remission. Relationship with cardiometabolic risk
Authors: Valassi Elena , Manichanh Chaysavanh , Amodru Vincent , Fernández Pedro González , Gaztambide Sonia , Yañez Francisca , Martel-Duguech Luciana , Puig-Domingo Manel , Webb Susan M.
Published: June 2023

Background

Patients with Cushing’s disease (CD) in remission maintain an increased cardiovascular risk. Impaired characteristics of gut microbiome (dysbiosis) have been associated with several cardiometabolic risk factors.

Methods

Twenty-eight female non-diabetic patients with CD in remission with a mean ± SD) age of 51 ± 9 years, mean ( ± SD) BMI, 26 ± 4, median (IQR) duration of remission, 11(4) years and 24 gender-, age, BMI–matched controls were included. The V4 region of the bacterial 16S rDNA was PCR amplified and sequenced to analyse microbial alpha diversity (Chao 1 index, observed number of species, Shannon index) and beta diversity analysis through the Principal Coordinates Analysis (PCoA) of weighted and unweighted UniFrac distances. Inter-group difference in microbiome composition was analysed using MaAsLin2.

Results

The Chao 1 index was lower in CD as compared with controls (Kruskal-Wallis test, q = 0.002), indicating lower microbial richness in the former. Beta diversity analysis showed that faecal samples from CS patients clustered together and separated from the controls (Adonis test, p<0.05). Collinsella, a genus form of the Actinobacteria phylum was present in CD patients only, whereas Sutterella, a genus from Proteobacteria phylum, was scarcely detectable/undetectable in CD patients as well as Lachnospira, a genus of the Lachnospiraceae family of the Firmicutes phylum. In CS, the Chao 1 index was associated with fibrinogen levels and inversely correlated with both triglyceride concentrations and the HOMA-IR index (p<0.05).

Conclusions

Patients with CS in remission have gut microbial dysbiosis which may be one of the mechanisms whereby cardiometabolic dysfunctions persist after “cure”.
Non-alcoholic fatty liver disease and incidence of microvascular complications of diabetes in patients with type 2 diabetes: a prospective cohort study
Authors: Deravi Niloofar , Dehghani Firouzabadi Fatemeh , Moosaie Fatemeh , Asadigandomani Hassan , Arab Bafrani Melika , Yoosefi Niyoosha , Poopak Amirhossein , Dehghani Firouzabadi Mohammad , Poudineh Mohadeseh , Rabizadeh Soghra , Kamel Ibrahim , Nakhjavani Manouchehr , Esteghamati Alireza
Published: June 2023

Objective

To investigate the association between non-alcoholic fatty liver disease (NAFLD) and liver enzymes with the incidence of microvascular complications (neuropathy, retinopathy, and nephropathy) in a cohort of Iranian patients with type 2 diabetes.

Methods

For a total population of 3123 patients with type 2 diabetes, a prospective study was designed for 1215 patients with NAFLD and 1908 gender and age-matched control patients without NAFLD. The two groups were followed for a median duration of 5 years for the incidence of microvascular complications. The association between having NAFLD, the level of liver enzymes, aspartate aminotransferase to platelet ratio index (APRI), Fibrosis-4 (FIB-4) value, and the incidence risk of diabetic retinopathy, neuropathy, and nephropathy were assessed through logistic regression analysis.

Results

NAFLD was found to be associated with incidence of diabetic neuropathy and nephropathy (Odds ratio: 1.338 (95% confidence interval: 1.091-1.640) and 1.333 (1.007-1.764), respectively). Alkaline-phosphatase enzyme was found to be associated with higher risks of diabetic neuropathy and nephropathy ((Risk estimate: 1.002 (95% CI: 1.001-1.003) and 1.002 (1.001-1.004), respectively)). Moreover, gamma-glutamyl transferase was associated with a higher risk of diabetic nephropathy (1.006 (1.002-1.009). Aspartate aminotransferase and alanine aminotransferase were inversely associated with the risk of diabetic retinopathy (0.989 (0.979-0.998) and 0.990 (0.983-0.996), respectively). Furthermore, ARPI_T (1), ARPI_T (2), and ARPI_T (3) were shown to be associated with NAFLD (1.440 (1.061-1.954), 1.589 (1.163-2.171), and 2.673 (1.925, 3.710), respectively). However, FIB-4 score was not significantly associated with risk of microvascular complications.

Conclusion

Despite the benign nature of NAFLD, patients with type 2 diabetes should be always assessed for NAFLD to ensure early diagnosis and entry into proper medical care. Regular screenings of microvascular complications of diabetes is also suggested for these patients.
How does climate risk matter for corporate green innovation? Empirical evidence from heavy-polluting listed companies in China
Authors: Ling Shixian , Gao Hongfu
Published: June 2023

Chinese heavy-polluting companies have been facing enormous challenges in responding to climate risk and energy transformation. This paper uses panel regression model and investigates the impact of climate risk on corporate green innovation in Chinese heavy-polluting listed companies from 2011 to 2020. The empirical results show that climate risk adversely affects green innovation in heavy-polluting companies, and this effect persists throughout a series of robustness and endogeneity tests. Climate risk may affect corporate green innovation through decreasing R&D investment, lowing resource allocation efficiency and increasing company risk. Climate risk has a greater negative impact on mid-western, state-owned and large-size heavy-polluting companies, but can be mitigated by the development of green finance, digital finance and marketization. These findings may help heavy-polluting companies fully utilize existing resources, policies, and channels for green innovation and mitigate climate risks.
Case report: Prenatal diagnosis of rare chromosome mosaicism: discordant results between chorionic villi and amniotic fluid samples
Authors: Li Lingping , Liu Xijing , Li Qinqin , Zhang Lili , Xiong Yueyue , Liu Shanling , Wang He , Zhu Hongmei , Zhang Xuemei
Published: June 2023

Objective: We described a unique case of near-negative chromosome mosaicism in chorionic villi but complete monosomy X in amniotic fluid.

Methods: Chorionic villus sampling and amniocentesis were performed separately in the first and second trimesters. Chromosomal microarray (CMA) and rapid aneuploidy detection (QF-PCR and FISH) were performed on placental villi and uncultured amniotic fluid. After pregnancy termination, the placenta, umbilical cord, and fetal muscle tissues were sampled for FISH detection.

Results: The CMA revealed a lower signal from chromosome X in chorionic villi, with a copy number of 1.85, implying the presence of mosaic monosomy X. However, the QF-PCR and FISH results were nearly normal. In uncultured amniotic fluid, CMA and rapid aneuploidy detection indicated complete monosomy X. Across different sampling points on the aborted fetus, the FISH results varied from normal, to mosaic, and then complete monosomy X.

Conclusion: This case presents a rare and complex situation where sampling from uncultured chorionic villi indicated low-level chromosome mosaicism, while sampling from amniotic fluid revealed complete monosomy X. Although some of these discordant outcomes may be due to methodological limitations, we conclude that prenatal consultation should be combined with fetal ultrasound phenotype and genetic testing for a comprehensive evaluation of fetal genetic abnormalities.
Pediatric myelin oligodendrocyte glycoprotein antibody-associated disease in southern China: analysis of 93 cases
Authors: Li Xiaojing , Wu Wenlin , Hou Chi , Zeng Yiru , Wu Wenxiao , Chen Lianfeng , Liao Yinting , Zhu Haixia , Tian Yang , Peng Bingwei , Zheng Kelu , Shi Kaili , Li Ying , Gao Yuanyuan , Zhang Yani , Lin Haisheng , Chen Wen-Xiong
Published: June 2023

Objective

To study the clinical features of children diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in southern China.

Methods

Clinical data of children diagnosed with MOGAD from April 2014 to September 2021 were analyzed.

Results

A total of 93 children (M/F=45/48; median onset age=6.0 y) with MOGAD were involved. Seizures or limb paralysis was the most common onset or course symptom, respectively. The most common lesion locations in brain MRI, orbital MRI, and spinal cord MRI were basal ganglia and subcortical white matter, the orbital segment of the optic nerve, and the cervical segment, respectively. ADEM (58.10%) was the most common clinical phenotype. The relapse rate was 24.7%. Compared with the patients without relapse, relapsed patients had a longer interval from onset to diagnosis (median: 19 days VS 20 days) and higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer positively persistent (median: 3 months VS 24 months). All patients received IVMP plus IVIG at the acute phase, and 96.8% of patients achieved remission after one to three courses of treatment. MMF, monthly IVIG, and maintaining a low dose of oral prednisone were used alone or in combination as maintenance immunotherapy for relapsed patients and effectively reduced relapse. It transpired 41.9% of patients had neurological sequelae, with movement disorder being the most common. Compared with patients without sequelae, patients with sequelae had higher MOG antibody titer at onset (median: 1:32 VS 1:100) with longer persistence (median: 3 months VS 6 months) and higher disease relapse rate (14.8% VS 38.5%).

Conclusions

Results showed the following about pediatric MOGAD in southern China: the median onset age was 6.0 years, with no obvious sex distribution difference; seizure or limb paralysis, respectively, are the most common onset or course symptom; the lesions of basal ganglia, subcortical white matter, the orbital segment of the optic nerve, and cervical segment were commonly involved in the CNS MRI; ADEM was the most common clinical phenotype; most had a good response to immunotherapy; although the relapse rate was relatively high, MMF, monthly IVIG and a low dose of oral prednisone might effectively reduce relapse; neurological sequelae were common, and possibly associated with MOG antibody status and disease relapse.
Telitacicept for autoimmune nephropathy
Authors: Cai Jingjing , Gao Dan , Liu Dongwei , Liu Zhangsuo
Published: June 2023

B cells and the humoral immunity are important players in the pathogenesis of autoimmune diseases. BAFF (also known as BLYS) and a proliferation-inducing ligand APRIL are required for the maintenance of the B-cell pool and humoral immunity. BAFF and APRIL can promote B-cell differentiation, maturation, and plasma cell antibody secretion. BAFF/APRIL overexpression has been identified in several autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, IgA nephropathy, etc. Telitacicept, a novel fully human TACI-Fc fusion protein that binds both BAFF and APRIL, was approved in China in March 2021 for the treatment of systemic lupus erythematosus at a recommended dose of 160 mg/w subcutaneously and is in clinical trials for the treatment of multiple indications in other autoimmune diseases. In this review, we explored telitacicept’s mechanism of action and clinical data. In addition, the immune features of autoimmune nephropathy were discussed, emphasizing lupus nephritis, IgA nephropathy, and membranous nephropathy.
Variable neutralizing antibody responses to 10 SARS-CoV-2 variants in natural infection with wild- type (B.1) virus, Kappa (B.1.617.1), and Delta (B.1.617.2) variants and COVISHIELD vaccine immunization in India: utility of the MSD platform
Authors: Patil Rajashree , Palkar Sonali , Mishra Akhileshchandra , Patil Rahul , Arankalle Vidya
Published: June 2023

For the efficacy of COVID-19 vaccines, emergence of variants accumulating immune-escape mutations remains a major concern. We analyzed the anti-variant (n = 10) neutralization activity of sera from COVID-19 patients infected with Wuhan (B.1), Kappa, and Delta variants and COVISHIELD vaccine recipients with (prepositives) or without (prenegatives) prior antibody positivity using V- PLEX ACE2 Neutralization Kit from MSD. MSD and PRNT50 correlated well (r = 0.76–0.83, p < 0.0001). Despite the least antibody positivity in Kappa patients, anti-variant neutralizing antibody (Nab) levels in the responders were comparable with Delta patients. Vaccinees sampled at 1 month (PD2-1) and 6 months (PD2-6) post-second dose showed the highest seropositivity and Nab levels against the Wuhan strain. At PD2-1, the responder rate was variant-dependent and 100% respectively in prenegatives and prepositives. Nab levels against B.1.135.1, B.1.620, B.1.1.7+E484K (both groups), AY.2 (prenegatives), and B.1.618 (prepositives) were lower than that of Wuhan. At PD2-6, positivity decreased to 15.6%–68.8% in the prenegatives; 3.5%–10.7% of prepositives turned negative for the same four variants. As against the decline in Nab levels in 9/10 variants (prenegatives), a further reduction was seen against the same four variants in the prepositives. These variants possess immune-evasion-associated mutations in the RBD/S region. In conclusion, our data show that the Nab response of patients to multiple variants depends on the infecting variant. We confirm superiority of hybrid immunity in neutralizing multiple variants. Depending on the infecting variant pre- or postvaccination, immune response to different vaccines in different populations will vary and impact protection against emerging variants. The MSD platform provides an excellent alternative to live virus/pseudovirus neutralization tests.
Cell metabolism-based optimization strategy of CAR-T cell function in cancer therapy
Authors: Li Wenshuai , Pan Xuanxuan , Chen Lirong , Cui Haoshu , Mo Shaocong , Pan Yida , Shen Yuru , Shi Menglin , Wu Jianlin , Luo Feifei , Liu Jie , Li Na
Published: June 2023

Adoptive cell therapy (ACT) using chimeric antigen receptor (CAR)-modified T cells has revolutionized the field of immune-oncology, showing remarkable efficacy against hematological malignancies. However, its success in solid tumors is limited by factors such as easy recurrence and poor efficacy. The effector function and persistence of CAR-T cells are critical to the success of therapy and are modulated by metabolic and nutrient-sensing mechanisms. Moreover, the immunosuppressive tumor microenvironment (TME), characterized by acidity, hypoxia, nutrient depletion, and metabolite accumulation caused by the high metabolic demands of tumor cells, can lead to T cell “exhaustion” and compromise the efficacy of CAR-T cells. In this review, we outline the metabolic characteristics of T cells at different stages of differentiation and summarize how these metabolic programs may be disrupted in the TME. We also discuss potential metabolic approaches to improve the efficacy and persistence of CAR-T cells, providing a new strategy for the clinical application of CAR-T cell therapy.
Stromal circuits involving tumor-associated macrophages and cancer-associated fibroblasts
Authors: Timperi Eleonora , Romano Emanuela
Published: June 2023

The tumor associated macrophages (TAM) represent one of most abundant subpopulations across several solid cancers and their number/frequency is associated with a poor clinical outcome. It has been clearly demonstrated that stromal cells, such as the cancer associated fibroblasts (CAFs), may orchestrate TAM recruitment, survival and reprogramming. Today, single cell-RNA sequencing (sc-RNA seq) technologies allowed a more granular knowledge about TAMs and CAFs phenotypical and functional programs. In this mini-review we discuss the recent discoveries in the sc-RNA seq field focusing on TAM and CAF identity and their crosstalk in the tumor microenvironment (TME) of solid cancers.
Long-Term Chili Monoculture Alters Environmental Variables Affecting the Dominant Microbial Community in Rhizosphere Soil
Authors: Chen Wenjing , Guo Xiaodong , Guo Quanen , Tan Xuelian , Wang Zhigang
Published: June 2023

Graphical Abstract

Long-term chili monoculture alters environmental variables affecting the dominant microbial community in rhizosphere soil.
Genomic characterization of the rotavirus G3P[8] strain in vaccinated children, reveals possible reassortment events between human and animal strains in Manhiça District, Mozambique
Authors: Manjate Filomena , João Eva D. , Mwangi Peter , Chirinda Percina , Mogotsi Milton , Messa Augusto , Garrine Marcelino , Vubil Delfino , Nobela Nélio , Nhampossa Tacilta , Acácio Sozinho , Tate Jacqueline E. , Parashar Umesh , Weldegebriel Goitom , Mwenda Jason M. , Alonso Pedro L. , Cunha Celso , Nyaga Martin , Mandomando Inácio
Published: June 2023

Mozambique introduced the rotavirus vaccine (Rotarix®; GlaxoSmithKline Biologicals, Rixensart, Belgium) in 2015, and since then, the Centro de Investigação em Saúde de Manhiça has been monitoring its impact on rotavirus-associated diarrhea and the trend of circulating strains, where G3P[8] was reported as the predominant strain after the vaccine introduction. Genotype G3 is among the most commonly detected Rotavirus strains in humans and animals, and herein, we report on the whole genome constellation of G3P[8] detected in two children (aged 18 months old) hospitalized with moderate-to-severe diarrhea at the Manhiça District Hospital. The two strains had a typical Wa-like genome constellation (I1-R1-C1-M1-A1-N1-T1-E1-H1) and shared 100% nucleotide (nt) and amino acid (aa) identities in 10 gene segments, except for VP6. Phylogenetic analysis demonstrated that genome segments encoding VP7, VP6, VP1, NSP3, and NSP4 of the two strains clustered most closely with porcine, bovine, and equine strains with identities ranging from 86.9–99.9% nt and 97.2–100% aa. Moreover, they consistently formed distinct clusters with some G1P[8], G3P[8], G9P[8], G12P[6], and G12P[8] strains circulating from 2012 to 2019 in Africa (Mozambique, Kenya, Rwanda, and Malawi) and Asia (Japan, China, and India) in genome segments encoding six proteins (VP2, VP3, NSP1-NSP2, NSP5/6). The identification of segments exhibiting the closest relationships with animal strains shows significant diversity of rotavirus and suggests the possible occurrence of reassortment events between human and animal strains. This demonstrates the importance of applying next-generation sequencing to monitor and understand the evolutionary changes of strains and evaluate the impact of vaccines on strain diversity.
c-Abl tyrosine kinase down-regulation as target for memory improvement in Alzheimer’s disease
Authors: León Rilda , Gutiérrez Daniela A. , Pinto Claudio , Morales Cristian , de la Fuente Catalina , Riquelme Cristóbal , Cortés Bastián I. , González-Martin Adrián , Chamorro David , Espinosa Nelson , Fuentealba Pablo , Cancino Gonzalo I. , Zanlungo Silvana , Dulcey Andrés E. , Marugan Juan J. , Álvarez Rojas Alejandra
Published: June 2023

Background

Growing evidence suggests that the non-receptor tyrosine kinase, c-Abl, plays a significant role in the pathogenesis of Alzheimer’s disease (AD). Here, we analyzed the effect of c-Abl on the cognitive performance decline of APPSwe/PSEN1ΔE9 (APP/PS1) mouse model for AD.

Methods

We used the conditional genetic ablation of c-Abl in the brain (c-Abl-KO) and pharmacological treatment with neurotinib, a novel allosteric c-Abl inhibitor with high brain penetrance, imbued in rodent’s chow.

Results

We found that APP/PS1/c-Abl-KO mice and APP/PS1 neurotinib-fed mice had improved performance in hippocampus-dependent tasks. In the object location and Barnes-maze tests, they recognized the displaced object and learned the location of the escape hole faster than APP/PS1 mice. Also, APP/PS1 neurotinib-fed mice required fewer trials to reach the learning criterion in the memory flexibility test. Accordingly, c-Abl absence and inhibition caused fewer amyloid plaques, reduced astrogliosis, and preserved neurons in the hippocampus.

Discussion

Our results further validate c-Abl as a target for AD, and the neurotinib, a novel c-Abl inhibitor, as a suitable preclinical candidate for AD therapies.
Physical activity and the brain myelin content in humans
Authors: Kujawa Mariusz J. , Marcinkowska Anna B. , Grzywińska Małgorzata , Waśkow Monika , Romanowski Alexander , Szurowska Edyta , Winklewski Paweł J. , Szarmach Arkadiusz
Published: June 2023

New imaging sequences and biophysical models allow adopting magnetic resonance imaging (MRI) for in vivo myelin mapping in humans. Understanding myelination and remyelination processes in the brain is fundamental from the perspective of proper design of physical exercise and rehabilitation schemes that aim to slow down demyelination in the aging population and to induce remyelination in patients with neurodegenerative diseases. Therefore, in this review we strive to provide a state-of-the art summary of the existing MRI studies in humans focused on the effects of physical activity on myelination/remyelination. We present and discuss four cross-sectional and four longitudinal studies and one case report. Physical activity and an active lifestyle have a beneficial effect on the myelin content in humans. Myelin expansion can be induced in humans throughout the entire lifespan by intensive aerobic exercise. Additional research is needed to determine (1) what exercise intensity (and cognitive novelty, which is embedded in the exercise scheme) is the most beneficial for patients with neurodegenerative diseases, (2) the relationship between cardiorespiratory fitness and myelination, and (3) how exercise-induced myelination affect cognitive abilities.
Effectiveness of internet-based CBT-I for the treatment of chronic subthreshold to moderate insomnia
Authors: Theppornpitak Wongpitak , Hemrungrojn Solaphat , Thienwiwatnukul Krittapas , Muntham Dittapol , Chirakalwasan Naricha , Srisawart Puntarik
Published: June 2023

Study objectives

To study the effectiveness of the first internet-based cognitive behavioral therapy for insomnia (CBT-i) in Thailand, using the Nitra application, for chronic subthreshold to moderate insomnia treatment.

Methods

An interventional study without a control group was conducted between January and June 2022. Participants were adults aged 18 years old and older with subthreshold to moderate severity of chronic insomnia (insomnia severity index (ISI) of 8–21) and had mean sleep efficiency <85% from baseline sleep diaries. Baseline sleep characteristics were obtained from questionnaires and sleep diaries from the Nitra application for 2 weeks. Eligible participants continued using the Nitra application for 4 weeks during the intervention period. Interventions including sleep restriction, stimulus control, cognitive restructuring, relaxation techniques, and sleep hygiene education were implemented via the pre-programmed Nitra application. Post-intervention sleep characteristics were also obtained from questionnaires and sleep diaries from the Nitra application for another 1 week.

Results

A total of 40 participants completed the study. All participants had a baseline sleep efficiency of less than 85% with the majority of the participants having a sleep-onset insomnia problem (98%). For the primary outcome, sleep efficiency was significantly improved after using the Nitra application (p < 0.001). Self-reported total sleep time, sleep onset latency, wake after sleep onset, early morning awakening, ISI, Pittsburgh Sleep Quality Index (PSQI), and average subjective sleep quality were also significantly improved (p < 0.001 for all parameters except p = 0.017 for total sleep time and p = 0.018 for wake after sleep onset). Participants who had a low baseline ISI and went to bed and woke up within 30 minutes of a designated bedtime and wake-up time recommended by the Nitra application for ≥70% of all nights demonstrated an increased chance of achieving normal sleep efficiency after using the Nitra application.

Conclusion

This first internet-based CBT-i in Thailand, using the Nitra application, effectively improved sleep efficiency and other sleep parameters in chronic subthreshold to moderate insomnia.
Global trends in COVID-19 Alzheimer's related research: a bibliometric analysis
Authors: Cao Chenjun , Li Sixin , Zhou Gaoya , Xu Caijuan , Chen Xi , Qiu Huiwen , Li Xinyu , Liu Ying , Cao Hui , Bi Changlong
Published: June 2023

Background

The COVID-19 pandemic has significantly impacted public health, putting people with Alzheimer's disease at significant risk. This study used bibliometric analysis method to conduct in-depth research on the relationship between COVID-19 and Alzheimer's disease, as well as to predict its development trends.

Methods

The Web of Science Core Collection was searched for relevant literature on Alzheimer's and Coronavirus-19 during 2019–2023. We used a search query string in our advanced search. Using Microsoft Excel 2021 and VOSviewer software, a statistical analysis of primary high-yield authors, research institutions, countries, and journals was performed. Knowledge networks, collaboration maps, hotspots, and regional trends were analyzed using VOSviewer and CiteSpace.

Results

During 2020–2023, 866 academic studies were published in international journals. United States, Italy, and the United Kingdom rank top three in the survey; in terms of productivity, the top three schools were Harvard Medical School, the University of Padua, and the University of Oxford; Bonanni, Laura, from Gabriele d'Annunzio University (Italy), Tedeschi, Gioacchino from the University of Campania Luigi Vanvitelli (Italy), Vanacore, Nicola from Natl Ctr Dis Prevent and Health Promot (Italy), Reddy, P. Hemachandra from Texas Tech University (USA), and El Haj, Mohamad from University of Nantes (France) were the authors who published the most articles; The Journal of Alzheimer's Disease is the journals with the most published articles; “COVID-19,” “Alzheimer's disease,” “neurodegenerative diseases,” “cognitive impairment,” “neuroinflammation,” “quality of life,” and “neurological complications” have been the focus of attention in the last 3 years.

Conclusion

The disease caused by the COVID-19 virus infection related to Alzheimer's disease has attracted significant attention worldwide. The major hot topics in 2020 were: “Alzheimer' disease,” COVID-19,” risk factors,” care,” and “Parkinson's disease.” During the 2 years 2021 and 2022, researchers were also interested in “neurodegenerative diseases,” “cognitive impairment,” and “quality of life,” which require further investigation.
Can prosocial values improve brain health?
Authors: Ibanez Agustin , Matallana Diana , Miller Bruce
Published: June 2023

Prosocial values play a critical role in promoting care and concern for the well-being of others and prioritizing the common good of society. Evidence from population-based reports, cognitive neuroscience, and clinical studies suggests that these values depend on social cognition processes, such as empathy, deontological moral cognition, moral emotions, and social cooperation. Additionally, indirect evidence suggests that various forms of prosocial behaviors are associated with positive health outcomes at the behavioral, cardiovascular, immune, stress-related, and inflammatory pathways. However, it is unclear whether prosociality can positively influence brain health outcomes. In this perspective, we propose that prosocial values are not only influenced by brain conditions but could also potentially play a role in protecting brain health. We review studies from various fields that support this claim, including recent reports of prosociality-based interventions impacting brain health. We then explore potential multilevel mechanisms, based on the reduction of allostatic overload at behavioral, cardiovascular, immune, stress-related, and inflammatory levels. Finally, we propose potential prosociality-based interventions for improving brain health in at-risk populations, such as psychiatric and neurological patients, and individuals exposed to poverty or violence. Our perspective suggests that prosocial values may play a role in promoting and maintaining healthy brains.
The effects of layer-wise relevance propagation-based feature selection for EEG classification: a comparative study on multiple datasets
Authors: Nam Hyeonyeong , Kim Jun-Mo , Choi WooHyeok , Bak Soyeon , Kam Tae-Eui
Published: June 2023

Introduction

The brain-computer interface (BCI) allows individuals to control external devices using their neural signals. One popular BCI paradigm is motor imagery (MI), which involves imagining movements to induce neural signals that can be decoded to control devices according to the user's intention. Electroencephalography (EEG) is frequently used for acquiring neural signals from the brain in the fields of MI-BCI due to its non-invasiveness and high temporal resolution. However, EEG signals can be affected by noise and artifacts, and patterns of EEG signals vary across different subjects. Therefore, selecting the most informative features is one of the essential processes to enhance classification performance in MI-BCI.

Methods

In this study, we design a layer-wise relevance propagation (LRP)-based feature selection method which can be easily integrated into deep learning (DL)-based models. We assess its effectiveness for reliable class-discriminative EEG feature selection on two different publicly available EEG datasets with various DL-based backbone models in the subject-dependent scenario.

Results and discussion

The results show that LRP-based feature selection enhances the performance for MI classification on both datasets for all DL-based backbone models. Based on our analysis, we believe that it can broad its capability to different research domains.
Characterization of global research trends and prospects on platinum-resistant ovarian cancer: a bibliometric analysis
Authors: Duan Yuanqiong , Zhang Peixuan , Zhang Tianyue , Zhou Lu , Yin Rutie
Published: June 2023

Background

In the last decades, growing attention has been focused on identifying effective therapeutic strategies in the orphan clinical setting of women with platinum-resistant ovarian cancer (PROC), generating thousands of original articles. However, the literature involving bibliometric analysis of PROC has not been published yet.

Objective

This study hopes to gain a better understanding of the hot spots and trends in PROC by conducting a bibliometric analysis, as well as identify potential new research directions.

Methods

We searched the Web of Science Core Collection (WOSCC) for PROC-related articles published between 1990 and 2022. CiteSpace 6.1.R2 and VOS viewer 1.6.18.0 were primarily utilized to evaluate the contribution and co-occurrence relationships of various countries and regions, institutes, and journals and to identify research hotspots and promising future trends in this research field.

Results

A total of 3,462 Web of Science publications were retrieved that were published in 671 academic journals by 1135 authors from 844 organizations in 75 countries and regions. The United States was the leading contributor in this field, and the University of Texas MD Anderson Cancer Center was the most productive institution. Gynecologic Oncology was the most productive journal, while the Journal of Clinical Oncology was the most cited and influential. Co-citation cluster labels revealed the characteristics of seven major clusters, including synthetic lethality, salvage treatment, human ovarian-carcinoma cell line, PARP inhibitor resistance, antitumor complexes, folate receptor, and targeting platinum-resistant disease. Keywords and references burst detection indicated that biomarkers, genetic and phenotypic changes, immunotherapy, and targeted therapy were the most recent and most significant aspects of PROC research.

Conclusion

This study conducted a comprehensive review of PROC research using bibliometric and visual techniques. Understanding the immunological landscape of PROC and identifying the population that can benefit from immunotherapy, especially in combination with other therapeutic options (such as chemotherapy and targeted therapy), will continue to be the focal point of research.
Prognostic significance of systemic immune-inflammation index in patients with ovarian cancer: a meta-analysis
Authors: Mao Huaying , Yang Fan
Published: June 2023

Background

The prognosis of several malignancies has been influenced by the systemic immune-inflammation index (SII); however, its association with the prognostic outcome of ovarian cancer (OC) remains controversial. The present meta-analysis focused on the systemic and comprehensive identification of the role of SII in predicting OC prognosis.

Methods

We searched the Web of Science, PubMed, Cochrane Library, Embase, and China National Knowledge Infrastructure (CNKI) from inception until March 6, 2023. To predict the prognostic value of SII for overall survival (OS) and progression-free survival (PFS) in patients with OC, we calculated pooled hazard ratios (HRs) and corresponding 95% confidence intervals (CIs).

Results

The meta-analysis included six studies involving 1546 patients. The combined results showed that a high SII was significantly associated with poor OS (HR=2.70, 95% CI=1.98–3.67, p<0.001) and poor PFS (HR=2.71, 95% CI=1.78–4.12, p<0.001) in OC patients. These results were confirmed using subgroup and sensitivity analyses.

Conclusion

Our results concluded that a high SII significantly predicted poor OS and PFS in patients with OC. Therefore, it can be speculated that the SII may have an independent effect on the prognosis of OC.
Case Report: Scleral hyperpigmentation associated with oral hydroxychloroquine use
Authors: Maretz Caroline , Omoruyi Felix , Wozniak Rachel A. F.
Published: June 2023

Hydroxychloroquine (HCQ) is a commonly used medication for its immunosuppressive and dermatologic effects. It has known ocular side effects, which include retinopathy, corneal deposits, and choroidal thinning. Herein, we report the first known case of HCQ-induced hyperpigmentation of the sclera. A 75-year-old female presented after 10 months of gradual progression of painless blue-gray discoloration of the bilateral sclera, fingernails, and lower extremities secondary to oral HCQ therapy. Cessation of the drug led to a partial reversal of the hyperpigmentation at 5 months, further supporting HCQ as the causative agent. Hyperpigmentation reactions can be distressing to patients and lead to decreased medication adherence; given the widespread use of HCQ, it is important to increase awareness of this potential drug reaction.