bluuebunny/crossref_metadata_2025 huggingface dataset:
Case report: First case of pemetrexed plus cisplatin-induced immune hemolytic anemia in a patient with lung adenocarcinoma
Authors: Lu Hongkai , Wang Na , Wang Peng , Zhang Haolin , Zhao Ru , Liu Hongju , He Xirong , Liu Zeya , Chang Yue , Cao Yongtong , Wang Shiyao
Published: August 2022

Background

Drug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening drug-related complication. There are no previous reports of pemetrexed plus cisplatin as first-line chemotherapy for non-small cell lung cancer, resulting in DIIHA.

Case presentation

In this report, a patient with advanced-stage lung adenocarcinoma developed severe immune hemolytic anemia 21 days after pemetrexed plus cisplatin chemotherapy. Laboratory findings showed severe hemolysis, including a rapid decrease in hemoglobin (HGB) and an elevated level of reticulocytes (Rets), indirect bilirubin (IBIL), and lactate dehydrogenase (LDH). A workup for the possibility of DIIHA was performed, including a direct antiglobulin test (DAT), a test in the presence of the soluble drug, and a drug-treated red blood cell (RBC) test. It showed a strongly positive (3+) result for anti-C3d but not for anti-immunoglobin G (IgG) in DAT. Enzyme-treated RBCs reacted weakly with the patient's serum and pemetrexed when complement was added. In addition, the patient's serum and normal sera were reactive with cisplatin-treated RBCs. However, eluates from the patient's RBCs and diluted normal sera were non-reactive with cisplatin-coated RBCs. Untreated and enzyme-treated RBCs reacted with the patient's serum in the presence of soluble cisplatin. In vitro serological tests suggested that complement-dependent pemetrexed antibodies and cisplatin-associated non-immunologic protein adsorption (NIPA) might combine to cause immune hemolytic anemia. The patient's anemia gradually recovered when pemetrexed and cisplatin were discontinued.

Conclusion

This rare case demonstrated that complement-dependent pemetrexed antibodies and cisplatin-associated NIPA might occur simultaneously in a patient with DIIHA.
Chronic kidney disease is potentially an independent prognostic factor for death in Stevens-Johnson syndrome and toxic epidermal necrolysis patients
Authors: Rattanakaemakorn Ploysyne , Palakornkitti Pasita , Pinyowiwat Prinpat , Jedee Phatphitcha , Thadanipon Kunlawat
Published: August 2022

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are mucocutaneous conditions associated with high mortality and morbidity. Although several prognostic factors have been proposed, some may have yet to be identified. A 14-year retrospective cohort study of patients with SJS/TEN was conducted at a university-based hospital in Bangkok, Thailand, to explore additional prognostic factors for mortality of patients with SJS/TEN. Medical records of all patients aged ≥18 years who were diagnosed with SJS, SJS-TEN overlap, or TEN between 2007 and 2020 were reviewed. Univariate and multivariate analyses were performed to examine associations between death and potential prognostic factors. A total of 76 patients with a mean age of 52 years were enrolled. Among them, 46, 15, and 15 patients were diagnosed with SJS, SJS-TEN overlap, and TEN, respectively. Overall, 10 patients deceased, marking a mortality rate of 13.2%. Based on an algorithm for assessment of drug causality for epidermal necrolysis, drug was the major cause of disease (96.1%). Allopurinol and trimethoprim/sulfamethoxazole were the most frequent culprit drugs. Univariate analysis revealed nine prognostic factors related to death, i.e., age, malignancy, chronic kidney disease (CKD), coronary artery disease, heart rate >120 beats/min, diagnoses of SJS-TEN overlap and TEN, blood urea nitrogen (BUN) >10 mmol/L, hemoglobin <10 g/dL, and serum albumin <2 g/dL. Causality with regard to drug, drug notoriety, time interval from drug intake to onset of reaction, and timing of culprit drug withdrawal were not significantly associated with death. Four independent prognostic factors for mortality were identified from multivariate analysis, i.e., TEN (risk ratio [RR] 8.29, 95% confidence interval [CI]: 2.71–25.38), malignancy (RR 3.34, 95% CI: 1.68–6.69), BUN >10 mmol/L (RR 3.02, 95% CI: 1.28–7.14), and early-stage CKD (RR 4.81, 95% CI: 2.49–9.28). Our findings suggest that CKD is an independent prognostic factor for mortality of patients with SJS/TEN besides those from the SCORTEN.
Fertility-sparing treatment for endometrial cancer and atypical endometrial hyperplasia in patients with Lynch Syndrome: Molecular diagnosis after immunohistochemistry of MMR proteins
Authors: Catena Ursula , Della Corte Luigi , Raffone Antonio , Travaglino Antonio , Lucci Cordisco Emanuela , Teodorico Elena , Masciullo Valeria , Bifulco Giuseppe , Di Spiezio Sardo Attilio , Scambia Giovanni , Fanfani Francesco
Published: August 2022

Introduction

Lynch Syndrome (LS) represents the hereditary condition that is most frequently associated with endometrial cancer (EC). The aim of this study is to assess the presence of Lynch Syndrome (LS) in young women with mismatch repair (MMR)-deficient atypical endometrial hyperplasia (AEH) and non-myoinvasive FIGO G1 endometrioid EC and its possible impact on the outcome of conservative treatment.

Methods

Six MMR-deficient cases identified from a previous cohort of 69 conservatively treated patients were selected to be screened for germline mutations in MMR genes. In each patient, the outcomes of conservative treatment for AEH and EEC, including response, relapse, progression, and pregnancy, were assessed.

Results

Five out of 6 patients underwent genetic test for LS. Three out of these 5 patients showed a positive genetic test. Patient 1 showed the c.942 + 2 T>A heterozygous variant of MSH2 mutation; after 12 months of complete response, she had relapse and progression of disease. Patient 4 showed the c.2459-1G>C variant of MSH2 mutation; after complete response, she failed to achieve pregnancy; she had relapse after 24 months and underwent hysterectomy. Patient 6 showed the c.803 + 1 heterozygous variant of PMS2 mutation; she had relapse of disease after 18 months from the first complete response and then underwent hysterectomy.

Conclusions

In this series, 3 out of 6 women with MMR-deficiency had LS. None of the patients achieved pregnancy, and those who responded to treatment had subsequent relapse of disease. Patients undergoing fertility-sparing treatment for atypical endometrial hyperplasia and endometrial cancer should perform MMR immunohistochemical analysis in order to screen LS.
The prevalence of sensory changes in post-COVID syndrome: A systematic review and meta-analysis
Authors: Trott Mike , Driscoll Robin , Pardhan Shahina
Published: August 2022

Post-COVID syndrome can be defined as symptoms of COVID-19 that persist for longer than 12 weeks, with several studies reporting persistent symptoms relating to the sensory organs (eyes, ears, and nose). The aim of this systematic review was to examine the prevalence of persistent anosmia, hyposmia, ageusia, and hypogeusia, as well as eye/vision and ear/hearing related long-COVID symptoms. Authors searched the electronic databases from inception to November 2021. Search terms included words related to long-COVID, smell, taste, eyes/vision, and ears/hearing, with all observational study designs being included. A random effects meta-analysis was undertaken, calculating the prevalence proportions of anosmia, hyposmia, ageusia, and hypogeusia, respectively. From the initial pool, 21 studies met the inclusion criteria (total n 4,707; median n per study 125; median age = 49.8; median percentage female = 59.2%) and 14 were included in the meta-analysis The prevalence of anosmia was 12.2% (95% CI 7.7–16.6%), hyposmia 29.9% (95% CI 19.9–40%), ageusia 11.7% (95% CI 6.1–17.3%), and hypogeusia 31.2% (95% 16.4–46.1%). Several eye/vision and ear/hearing symptoms were also reported. Considering that changes in the sensory organs are associated with decreases in quality of life, future research should examine the etiology behind the persistent symptoms.

Systematic review registration

[www.crd.york.ac.uk/prospero], identifier [CRD42021292804].
A case report of cerebral venous sinus thrombosis presenting with rapidly progressive dementia
Authors: Li Yaqiang , Zhang Mei , Xue Min , Wei Ming , He Jiale , Dong Chunhui
Published: August 2022

Background

Cerebral venous sinus thrombosis (CVST) is a rare but serious and treatable cause of neurologic symptoms. Due to the variable clinical presentation, CVST was often misdiagnosed. According to published case reports, common clinical manifestations of CVST include headache, focal neurological deficit, epilepsy, papilledema, etc. It is rare, nevertheless, to mention cases of rapidly progressive dementia (RPD).

Case presentation

We reported a case of a 62-year-old retired male accountant, a Han Chinese from eastern China, who initially presented with slow response and memory decline. Until 2 months later, his memory declined and slow response deteriorated significantly, and he could not even complete simple tasks like brushing his teeth, washing his face, washing his feet, and dressing himself, and sometimes developed fecal incontinence. His neuropsychological test demonstrated severe cognitive decline. The cerebrospinal fluid (CSF) studies revealed markedly high opening pressure (260 mm of water), and coagulation tests indicated a mild elevation of D-Dimer of 1.19 mg/L. The magnetic resonance venography (MRV) showed thrombosis of the left transverse sinus, sigmoid sinus, and jugular venous bulb and was diagnosed as CVST. He switched from subcutaneous low molecular weight heparin (LMWH) and transitioned to oral anticoagulants at the time of discharge. The repeated CSF studies revealed normal opening pressure. After 5 days of anticoagulant treatment, his symptoms considerably improved, and a 1-month follow-up revealed that he had fully healed with no signs of recurrence.

Conclusion

This case demonstrated the clinical heterogeneity of CVST, which should be taken into account for differential diagnosis of RPD. This case study also offered fresh data for the categorization of the clinical traits and the diagnosis of CVST.
Technological evaluation of strategies to get out of bed by people with Parkinson's disease: Insights from multisite wearable sensors
Authors: Sringean Jirada , Thanawattano Chusak , Bhidayasiri Roongroj
Published: August 2022

Background

Difficulty getting out of bed is a common night-time and early morning manifestation of Parkinson's disease (PD), rated by 40% of the patients as their most concerning motor symptoms. However, current assessment methods are based on clinical interviews, video analysis, and clinical scales as objective outcome measures are not yet available.

Objective

To study the technical feasibility of multisite wearable sensors in the assessment of the supine-to-stand (STS) task as a determinant of the ability to get out of bed in patients with PD and age-matched control subjects, and develop relevant objective outcome measures.

Methods

The STS task was assessed in 32 patients with PD (mean Hoehn and Yahr; HY = 2.5) in the early morning before their first dopaminergic medication, and in 14 control subjects, using multisite wearable sensors (NIGHT-Recorder®; trunk, both wrists, and both ankles) in a sleep laboratory. Objective getting out of bed parameters included duration, onset, velocity and acceleration of truncal rotation, and angle deviation (a°) from the z-axis when subjects rose from the bed at different angles from the x-axis (10°, 15°, 30°, 45°, and 60°) as measures of truncal lateral flexion. Movement patterns were identified from the first body part or parts that moved. Correlation analysis was performed between these objective outcomes and standard clinical rating scales.

Results

Compared to control subjects, the duration of STS was significantly longer in patients with PD (p = 0.012), which is associated with a significantly slower velocity of truncal rotation (p = 0.003). Moderate and significant correlations were observed between the mean STS duration and age, and the Nocturnal Hypokinesia Questionnaire. The velocity of truncal rotation negatively and significantly correlated with HY staging. Any arm and leg moved together as the first movement significantly correlated with UPDRS-Axial and item #28. Several other correlations were also observed.

Conclusion

Our study was able to demonstrate the technical feasibility of using multisite wearable sensors to quantitatively assess early objective outcome measures of the ability of patients with PD to get out of bed, which significantly correlated with axial severity scores, suggesting that axial impairment could be a contributing factor in difficulty getting out of bed. Future studies are needed to refine these outcome measures for use in therapeutic trials related to nocturia or early morning akinesia in PD.
Floral nectar microbial communities exhibit seasonal shifts associated with extreme heat: Potential implications for climate change and plant-pollinator interactions
Authors: Russell Kaleigh A. , McFrederick Quinn S.
Published: August 2022

Floral nectar contains vital nutrients for pollinators, including sugars, amino acids, proteins, and secondary compounds. As pollinators forage, they inoculate nectar with bacteria and fungi. These microbes can colonize nectaries and alter nectar properties, including volume and chemistry. Abiotic factors, such as temperature, can influence microbial community structure and nectar traits. Considering current climate change conditions, studying the effects of increased temperature on ecosystem processes like pollination is ever more important. In a manipulative field experiment, we used a passive-heating technique to increase the ambient temperature of a California native plant, Penstemon heterophyllus, to test the hypothesis that temperatures elevated an average of 0.5°C will affect nectar properties and nectar-inhabiting microbial communities. We found that passive-heat treatment did not affect nectar properties or microbial communities. Penstemon heterophyllus fruit set also was not affected by passive-heat treatments, and neither was capsule mass, however plants subjected to heat treatments produced significantly more seeds than control. Although we conducted pollinator surveys, no pollinators were recorded for the duration of our experiment. A naturally occurring extreme temperature event did, however, have large effects on nectar sugars and nectar-inhabiting microbial communities. The initially dominant Lactobacillus sp. was replaced by Sediminibacterium, while Mesorhizobium, and Acinetobacter persisted suggesting that extreme temperatures can interrupt nectar microbiome community assembly. Our study indicates that the quality and attractiveness of nectar under climate change conditions could have implications on plant-pollinator interactions.
Untargeted metabolite profiling to elucidate rhizosphere and leaf metabolome changes of wheat cultivars (Triticum aestivum L.) treated with the plant growth-promoting rhizobacteria Paenibacillus alvei (T22) and Bacillus subtilis
Authors: Mashabela Manamele D. , Tugizimana Fidele , Steenkamp Paul A. , Piater Lizelle A. , Dubery Ian A. , Mhlongo Msizi I.
Published: August 2022

The rhizosphere is a highly complex and biochemically diverse environment that facilitates plant–microbe and microbe–microbe interactions, and this region is found between plant roots and the bulk soil. Several studies have reported plant root exudation and metabolite secretion by rhizosphere-inhabiting microbes, suggesting that these metabolites play a vital role in plant–microbe interactions. However, the biochemical constellation of the rhizosphere soil is yet to be fully elucidated and thus remains extremely elusive. In this regard, the effects of plant growth-promoting rhizobacteria (PGPR)–plant interactions on the rhizosphere chemistry and above ground tissues are not fully understood. The current study applies an untargeted metabolomics approach to profile the rhizosphere exo-metabolome of wheat cultivars generated from seed inoculated (bio-primed) with Paenibacillus (T22) and Bacillus subtilis strains and to elucidate the effects of PGPR treatment on the metabolism of above-ground tissues. Chemometrics and molecular networking tools were used to process, mine and interpret the acquired mass spectrometry (MS) data. Global metabolome profiling of the rhizosphere soil of PGPR-bio-primed plants revealed differential accumulation of compounds from several classes of metabolites including phenylpropanoids, organic acids, lipids, organoheterocyclic compounds, and benzenoids. Of these, some have been reported to function in plant–microbe interactions, chemotaxis, biocontrol, and plant growth promotion. Metabolic perturbations associated with the primary and secondary metabolism were observed from the profiled leaf tissue of PGPR-bio-primed plants, suggesting a distal metabolic reprograming induced by PGPR seed bio-priming. These observations gave insights into the hypothetical framework which suggests that PGPR seed bio-priming can induce metabolic changes in plants leading to induced systemic response for adaptation to biotic and abiotic stress. Thus, this study contributes knowledge to ongoing efforts to decipher the rhizosphere metabolome and mechanistic nature of biochemical plant–microbe interactions, which could lead to metabolome engineering strategies for improved plant growth, priming for defense and sustainable agriculture.
Screening and transcriptomic analysis of the ethanol-tolerant mutant Saccharomyces cerevisiae YN81 for high-gravity brewing
Authors: Yang Tianyou , Zhang Shishuang , Li Linbo , Tian Jing , Li Xu , Pan Yuru
Published: August 2022

Ethanol stress is one of the major limiting factors for high-gravity brewing. Breeding of yeast strain with high ethanol tolerance, and revealing the ethanol tolerance mechanism of Saccharomyces cerevisiae is of great significance to the production of high-gravity beer. In this study, the mutant YN81 was obtained by ultraviolet-diethyl sulfate (UV-DES) cooperative mutagenesis from parental strain CS31 used in high-gravity craft beer brewing. The ethanol tolerance experiment results showed that cell growth and viability of YN81 were significantly greater than that of CS31 under ethanol stress. The ethanol tolerance mechanisms of YN81 were studied through observation of cell morphology, intracellular trehalose content, and transcriptomic analysis. Results from scanning electron microscope (SEM) showed alcohol toxicity caused significant changes in the cell morphology of CS31, while the cell morphology of YN81 changed slightly, indicating the cell morphology of CS31 got worse (the formation of hole and cell wrinkle). In addition, compared with ethanol-free stress, the trehalose content of YN81 and CS31 increased dramatically under ethanol stress, but there was no significant difference between YN81 and CS31, whether with or without ethanol stress. GO functional annotation analysis showed that under alcohol stress, the number of membrane-associated genes in YN81 was higher than that without alcohol stress, as well as CS31, while membrane-associated genes in YN81 were expressed more than CS31 under alcohol stress. KEGG functional enrichment analysis showed unsaturated fatty acid synthesis pathways and amino acid metabolic pathways were involved in ethanol tolerance of YN81. The mutant YN81 and its ethanol tolerance mechanism provide an optimal strain and theoretical basis for high-gravity craft beer brewing.
Genomic characterization and phylogenetic analysis of a novel Nairobi sheep disease genogroup Orthonairovirus from ticks, Southeastern China
Authors: Zhang Xu , Li Hang-Yuan , Shao Jian-Wei , Pei Ming-Chao , Cao Chong , Huang Fu-Qiang , Sun Ming-Fei
Published: August 2022

The increasing prevalence and transmission of tick-borne diseases, especially those emerging ones, have posed a significant threat to public health. Thus, the discovery of neglected pathogenic agents carried and transmitted by ticks is urgently needed. Using unbiased high-throughput sequencing, a novel Orthonairovirus designated as Meihua Mountain virus (MHMV), was identified in bloodsucking ticks collected from cattle and wild boars in Fujian province, Southeastern China. The full-length genome was determined by RT-PCR and RACE. Genomic architecture of MHMV shares typical features with orthonairoviruses. Phylogenetic analyses suggested that MHMV is clustered into the Nairobi sheep disease (NSD) genogroup of the genus Orthonairovirus and is closely related to the Hazara virus. The RdRp, GPC, and N protein of MHMV shares 62.3%–83.5%, 37.1%–66.1%, and 53.4%–77.3% amino acid identity with other NSD genogroup viruses, respectively, representing a novel species. The overall pooled prevalence of MHMV in ticks was 2.53% (95% CI: 1.62%–3.73%, 22 positives of 134 tick pools), with 7.38% (95% CI: 3.84%–12.59%, 11 positives of 18 pools) in Haemaphysalis hystricis, 6.02% (95% CI: 1.85%–14.22%, four positives of eight pools) in H. formosensis, 25.03% (95% CI: 9.23%–54.59%, six positive of eight pools) in Dermacentor taiwanensis, and 0.16% (95% CI: 0.01%–0.72%, one positive of 100 pools) in Rhipicephalus microplus. This study presented the first report of tick-carried Orthonairovirus in Fujian province and highlighted the broad geographic distribution and high genetic diversity of orthonairoviruses in China.
Impact of vanillin on postharvest disease control of apple
Authors: Wang Xiangyu , Zhang Xuemin , Sun Meng , Wang Li , Zou Yaoyuan , Fu Lin , Han Chuanyu , Li Anqing , Li Limei , Zhu Chunyu
Published: August 2022

Apple fruits are susceptible to infection by postharvest fungal pathogens, which may cause fruit decay and severe economic losses. This study investigated the antifungal spectrum of vanillin against common decay pathogens of apple and explored the antifungal mechanisms of vanillin in vitro. In vivo experiments were carried out to evaluate the effects of vanillin on apple postharvest disease control and fruit quality. Moreover, the induced resistance mechanism of vanillin on apple fruit was preliminarily explored. The results showed that vanillin has broad-spectrum antifungal effects, especially on Alternaria alternata. Vanillin could significantly inhibit the growth rate, mycelium biomass, and spore germination of pathogenic fungi by increasing the cell membrane permeability and lipid peroxidation. Importantly, vanillin treatment reduced the incidence of apple decay caused by A. alternata and Penicillium expansum, and contributed to improve fruit quality. Further studies indicated that vanillin could induce elevation in the activities of defense-related enzymes in apple fruit, such as phenylalanine ammonia-lyase (PAL), chitinase (CHI) and β-1,3-glucanase (β-1,3-GA), and increase total phenols and flavonoids contents. Generally, these results suggest that vanillin may contribute to the induced resistance of apple fruits to pathogenic fungi. To conclude, the results of this research provide theoretical foundations for the application of vanillin in the control of apple postharvest decay caused by fungal pathogens.
Quercetin positively affects gene expression profiles and metabolic pathway of antibiotic-treated mouse gut microbiota
Authors: Mi Wei , Hu Zhiyong , Xu Lanlan , Bian Xiangyu , Lian Wu , Yin Shuying , Zhao Shuying , Gao Weina , Guo Changjiang , Shi Tala
Published: August 2022

Quercetin has a wide range of biological properties that can be used to prevent or decrease particular inflammatory diseases. In this study, we aimed to investigate the gene expression profile and metabolic pathway of the gut microbiota of an antibiotic-treated mouse model administered quercetin. Blood, feces, and intestinal tissue samples were collected and metagenomic sequencing, enzyme-linked immunosorbent assay, and western blot analysis were used to detect variations. The results showed that the quercetin-treated group exhibited increased levels of health beneficial bacterial species, including Faecalibaculum rodentium (103.13%), Enterorhabdus caecimuris (4.13%), Eggerthella lenta (4%), Roseburia hominis (1.33%), and Enterorhabdus mucosicola (1.79%), compared with the model group. These bacterial species were positively related to butyrate, propionate, and intestinal tight junction proteins (zonula occludens-1 and occludin) expression, but negatively related to serum lipopolysaccharide and tumor necrosis factor-α level. In addition, the metabolic pathway analysis showed that dietary quercetin significantly enhanced spliceosomes (111.11%), tight junctions (62.96%), the citrate cycle (10.41%), pyruvate metabolism (6.95%), and lysine biosynthesis (5.06%), but decreasing fatty acid biosynthesis (23.91%) and N-glycan (7.37%) biosynthesis. Furthermore, these metabolic pathway changes were related to relative changes in the abundance of 10 Kyoto Encyclopedia of Genes and Genomes genes (K00244, K00341, K02946, K03737, K01885, k10352, k11717, k10532, K02078, K01191). In conclusion, dietary quercetin increased butyrate-producing bacterial species, and the acetyl-CoA-mediated increased butyrate accelerated carbohydrate, energy metabolism, reduced cell motility and endotoxemia, and increased the gut barrier function, thereby leading to healthy colonic conditions for the host.
Comparative transcriptome analysis revealed molecular mechanisms of peanut leaves responding to Ralstonia solanacearum and its type III secretion system mutant
Authors: Yang Yong , Chen Ting , Dai Xiaoqiu , Yang Dong , Wu Yushuang , Chen Huilan , Zheng Yixiong , Zhi Qingqing , Wan Xiaorong , Tan Xiaodan
Published: August 2022

Bacterial wilt caused by Ralstonia solanacearum is a serious soil-borne disease that limits peanut production and quality, but the molecular mechanisms of the peanut response to R. solanacearum remain unclear. In this study, we reported the first work analyzing the transcriptomic changes of the resistant and susceptible peanut leaves infected with R. solanacearum HA4-1 and its type III secretion system mutant strains by the cutting leaf method at different timepoints (0, 24, 36, and 72 h post inoculation). A total of 125,978 differentially expressed genes (DEGs) were identified and subsequently classified into six groups to analyze, including resistance-response genes, susceptibility-response genes, PAMPs induced resistance-response genes, PAMPs induced susceptibility-response genes, T3Es induced resistance-response genes, and T3Es induced susceptibility-response genes. KEGG enrichment analyses of these DEGs showed that plant-pathogen interaction, plant hormone signal transduction, and MAPK signaling pathway were the outstanding pathways. Further analysis revealed that CMLs/CDPKs-WRKY module, MEKK1-MKK2-MPK3 cascade, and auxin signaling played important roles in the peanut response to R. solanacearum. Upon R. solanacearum infection (RSI), three early molecular events were possibly induced in peanuts, including Ca2+ activating CMLs/CDPKs-WRKY module to regulate the expression of resistance/susceptibility-related genes, auxin signaling was induced by AUX/IAA-ARF module to activate auxin-responsive genes that contribute to susceptibility, and MEKK1-MKK2-MPK3-WRKYs was activated by phosphorylation to induce the expression of resistance/susceptibility-related genes. Our research provides new ideas and abundant data resources to elucidate the molecular mechanism of the peanut response to R. solanacearum and to further improve the bacterial wilt resistance of peanuts.
In-silico probing of AML related RUNX1 cancer-associated missense mutations: Predicted relationships to DNA binding and drug interactions
Authors: Ullah Hanif , Zhang Baoyun , Sharma Narendra Kumar , McCrea Pierre D. , Srivastava Yogesh
Published: August 2022

The molecular consequences of cancer associated mutations in Acute myeloid leukemia (AML) linked factors are not very well understood. Here, we interrogated the COSMIC database for missense mutations associated with the RUNX1 protein, that is frequently mis-regulated in AML, where we sought to identify recurrently mutated positions at the DNA-interacting interface. Indeed, six of the mutated residues, out of a total 417 residues examined within the DNA binding domain, evidenced reduced DNA association in in silico predictions. Further, given the prominence of RUNX1’s compromised function in AML, we asked the question if the mutations themselves might alter RUNX1’s interaction (off-target) with known FDA-approved drug molecules, including three currently used in treating AML. We identified several AML-associated mutations in RUNX1 that were calculated to enhance RUNX1’s interaction with specific drugs. Specifically, we retrieved data from the COSMIC database for cancer-associated mutations of RUNX1 by using R package “data.table” and “ggplot2” modules. In the presence of DNA and/or drug, we used docking scores and energetics of the complexes as tools to evaluate predicted interaction strengths with RUNX1. For example, we performed predictions of drug binding pockets involving Enasidenib, Giltertinib, and Midostaurin (AML associated), as well as ten different published cancer associated drug compounds. Docking of wild type RUNX1 with these 13 different cancer-associated drugs indicates that wild-type RUNX1 has a lower efficiency of binding while RUNX1 mutants R142K, D171N, R174Q, P176H, and R177Q suggested higher affinity of drug association. Literature evidence support our prediction and suggests the mutation R174Q affects RUNX1 DNA binding and could lead to compromised function. We conclude that specific RUNX1 mutations that lessen DNA binding facilitate the binding of a number of tested drug molecules. Further, we propose that molecular modeling and docking studies for RUNX1 in the presence of DNA and/or drugs enables evaluation of the potential impact of RUNX1 cancer associated mutations in AML.
Levetiracetam alleviates cognitive decline in Alzheimer’s disease animal model by ameliorating the dysfunction of the neuronal network
Authors: Zheng Xiang-Yu , Zhang Hai-Chen , Lv Yu-Dan , Jin Feng-Yan , Wu Xiu-Juan , Zhu Jie , Ruan Yang
Published: August 2022

Background

Patients with Alzheimer’s disease (AD) have a significantly higher risk of seizures than other individuals in an age-matched population, suggesting a close association between epilepsy and AD. We aimed to examine the effects of levetiracetam (LEV)—a drug for treating seizures—on learning and memory and the neuropathological features of AD.

Methods

We crossbred APP23 mice with microtubule-associated protein tau (MAPT) transgenic mice to generate APP23/MAPT mice. These mice were treated with different concentrations of LEV in the presence of kainic acid (KA) for 3 months.

Results

Low doses of LEV alleviated the effects of KA on memory defects in APP23/MAPT mice. Mechanistic investigations showed that low concentrations of LEV decreased tau phosphorylation by reducing the activities of cyclin-dependent kinase 5 and glycogen synthase kinase 3α/β, thus rescuing neurons from synaptic dystrophy and apoptosis. Low doses of LEV inhibited the effects of KA (i.e., inducing neuroinflammation and impairing the autophagy of amyloid β-peptide), thus improving cognitive decline. High concentrations of LEV decreased the production and deposition of amyloid β-peptide (Aβ) by reducing the expression of β-site APP-cleaving enzyme 1 and presenilin 1. However, high concentrations of LEV also induced neuronal apoptosis, decreased movement ability in mice, and did not alleviate cognitive decline in AD mice.

Conclusion

Our results support the hypothesis that aberrant network activity contributes to the synaptic and cognitive deficits in APP23/MAPT mice. A low concentration of LEV may help ameliorate abnormalities of AD; however, a high LEV concentration did not induce similar results.
Quantitative myelin-related maps from R1 and T2* ratio images using a single ME-MP2RAGE sequence in 7T MRI
Authors: Shim Jeong-Min , Cho Seo-Eun , Kang Seung-Gul , Kang Chang-Ki
Published: August 2022

Background: There still are limitations associated with quantifying myelin content using brain magnetic resonance imaging (MRI) despite several studies conducted on this subject. Therefore, this study aimed: (1) to propose a myelin-related mapping technique to obtain the quantitative R1/T2* (q-Ratio) that has the advantage of quick processing and less dependency on imaging parameters, (2) to validate this adapted q-Ratio method by comparing the quantitative myelin-related map with those acquired through an existing mapping method [T1-weighted/T2*-weighted (w-Ratio)], and (3) to determine the q-Ratio myelin-related values in the white and gray matter, and the relationship between the q-Ratio myelin-related value and cerebral volume size in regions of interest (ROIs) in a healthy population.

Methods: The multi-echo magnetization-prepared 2 rapid gradient echoes (ME-MP2RAGE) sequence was used in a 7 Tesla (7T) MRI for the acquisition of data regarding myelin content in 10 healthy participants. A correlation analysis was performed between myelin-related values obtained through the q-Ratio and w-Ratio methods. Additionally, myelin distribution was analyzed and compared in the white and gray matter, and the correlation between cerebral volume size and q-Ratio myelin-related value was analyzed in ROIs in the brain.

Results: The myelin-related maps acquired through the q-Ratio and w-Ratio methods were significantly correlated (p < 0.001), but the q-Ratio myelin-related map was much clearer. Additionally, the cerebral volume size in the gray matter was 399.40% larger than that in the white matter, but the q-Ratio myelin-related value in the gray matter was 80.83% lower than that of the white matter. Furthermore, volume size was positively correlated with q-Ratio myelin-related values in the white matter (r = 0.509, p = 0.006) but not in the gray matter (r = -0.133, p = 0.402).

Conclusions: In this study, we validated using a q-Ratio myelin-related map that was acquired in one imaging sequence at 7T MRI. In addition, we found a significant correlation between ROI volume size and the q-Ratio myelin-related value in the white matter but not in the gray matter. It is expected that this technique could be applied to the study of various neuropsychiatric diseases related to demyelination in the future.
Temporal dynamics of cholinergic activity in the septo-hippocampal system
Authors: Kopsick Jeffrey D. , Hartzell Kyle , Lazaro Hallie , Nambiar Pranav , Hasselmo Michael E. , Dannenberg Holger
Published: August 2022

Cholinergic projection neurons in the medial septum and diagonal band of Broca are the major source of cholinergic modulation of hippocampal circuit functions that support neural coding of location and running speed. Changes in cholinergic modulation are known to correlate with changes in brain states, cognitive functions, and behavior. However, whether cholinergic modulation can change fast enough to serve as a potential speed signal in hippocampal and parahippocampal cortices and whether the temporal dynamics in such a signal depend on the presence of visual cues remain unknown. In this study, we use a fiber-photometric approach to quantify the temporal dynamics of cholinergic activity in freely moving mice as a function of the animal’s movement speed and visual cues. We show that the population activity of cholinergic neurons in the medial septum and diagonal band of Broca changes fast enough to be aligned well with changes in the animal’s running speed and is strongly and linearly correlated to the logarithm of the animal’s running speed. Intriguingly, the cholinergic modulation remains strongly and linearly correlated to the speed of the animal’s neck movements during periods of stationary activity. Furthermore, we show that cholinergic modulation is unaltered during darkness. Lastly, we identify rearing, a stereotypic behavior where the mouse stands on its hindlimbs to scan the environment from an elevated perspective, is associated with higher cholinergic activity than expected from neck movements on the horizontal plane alone. Taken together, these data show that temporal dynamics in the cholinergic modulation of hippocampal circuits are fast enough to provide a potential running speed signal in real-time. Moreover, the data show that cholinergic modulation is primarily a function of the logarithm of the animal’s movement speed, both during locomotion and during stationary activity, with no significant interaction with visual inputs. These data advance our understanding of temporal dynamics in cholinergic modulation of hippocampal circuits and their functions in the context of neural coding of location and running speed.
Alteration of m6A epitranscriptomic tagging of ribonucleic acids after spinal cord injury in mice
Authors: Ni Shuangfei , Luo Zixiang , Fan Yonggang , Zhang Weixin , Peng Wei , Zhang Huafeng
Published: August 2022

The m6A methylation is reported to function in multiple physiological and pathological processes. However, the functional relevance of m6A modification to post-spinal cord injured (SCI) damage is not yet clear. In the present study, methylated RNA immunoprecipitation combined with microarray analysis showed that the global RNA m6A levels were decreased following SCI. Then, gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analyses were conducted to demonstrate the potential function of differential m6A-tagged transcripts and the altered transcripts with differential m6A levels. In addition, we found that the m6A “writer,” METTL3, significantly decreased after SCI in mice. The immunostaining validated that the expression of METTL3 mainly changed in GFAP or Iba-1+ cells. Together, this study shows the alteration of m6A modification following SCI in mice, which might contribute to the pathophysiology of the spinal cord after trauma.
Intrinsic brain activity reorganization contributes to long-term compensation of higher-order hearing abilities in single-sided deafness
Authors: Qiao Yufei , Zhu Min , Sun Wen , Sun Yang , Guo Hua , Shang Yingying
Published: August 2022

Single-sided deafness (SSD) is an extreme case of partial hearing deprivation and results in a significant decline in higher-order hearing abilities, including sound localization and speech-in-noise recognition. Clinical studies have reported that patients with SSD recover from these higher-order hearing abilities to some extent over time. Neuroimaging studies have observed extensive brain functional plasticity in patients with SSD. However, studies investigating the role of plasticity in functional compensation, particularly those investigating the relationship between intrinsic brain activity alterations and higher-order hearing abilities, are still limited. In this study, we used resting-state functional MRI to investigate intrinsic brain activity, measured by the amplitude of low-frequency fluctuation (ALFF), in 19 patients with left SSD, 17 patients with right SSD, and 21 normal hearing controls (NHs). All patients with SSD had durations of deafness longer than 2 years. Decreased ALFF values in the bilateral precuneus (PCUN), lingual gyrus, and left middle frontal gyrus were observed in patients with SSD compared with the values of NHs. Longer durations of deafness were correlated with better hearing abilities, as well as higher ALFF values in the left inferior parietal lobule, the angular gyrus, the middle occipital gyrus, the bilateral PCUN, and the posterior cingulate gyrus. Moreover, we observed a generally consistent trend of correlation between ALFF values and higher-order hearing abilities in specific brain areas in patients with SSD. That is, better abilities were correlated with lower ALFF values in the frontal regions and higher ALFF values in the PCUN and surrounding parietal-occipital areas. Furthermore, mediation analysis revealed that the ALFF values in the PCUN were a significant mediator of the relationship between the duration of deafness and higher-order hearing abilities. Our study reveals significant plasticity of intrinsic brain activity in patients with SSD and suggests that reorganization of intrinsic brain activity may be one of the compensatory mechanisms that facilitate improvement in higher-order hearing abilities in these patients over time.
Enhancing socio-emotional communication and quality of life in young cochlear implant recipients: Perspectives from parameter-specific morphing and caricaturing
Authors: Schweinberger Stefan R. , von Eiff Celina I.
Published: August 2022

The use of digitally modified stimuli with enhanced diagnostic information to improve verbal communication in children with sensory or central handicaps was pioneered by Tallal and colleagues in 1996, who targeted speech comprehension in language-learning impaired children. Today, researchers are aware that successful communication cannot be reduced to linguistic information—it depends strongly on the quality of communication, including non-verbal socio-emotional communication. In children with cochlear implants (CIs), quality of life (QoL) is affected, but this can be related to the ability to recognize emotions in a voice rather than speech comprehension alone. In this manuscript, we describe a family of new methods, termed parameter-specific facial and vocal morphing. We propose that these provide novel perspectives for assessing sensory determinants of human communication, but also for enhancing socio-emotional communication and QoL in the context of sensory handicaps, via training with digitally enhanced, caricatured stimuli. Based on promising initial results with various target groups including people with age-related macular degeneration, people with low abilities to recognize faces, older people, and adult CI users, we discuss chances and challenges for perceptual training interventions for young CI users based on enhanced auditory stimuli, as well as perspectives for CI sound processing technology.
Metformin use is associated with a reduced risk of cognitive impairment in adults with diabetes mellitus: A systematic review and meta-analysis
Authors: Zhang Jia-Hao , Zhang Xin-Yang , Sun Yan-Qiu , Lv Ren-Hua , Chen Mei , Li Meng
Published: August 2022

Objective

Controversy exists regarding the impact of metformin and whether it prevents or promotes the incidence of cognitive dysfunction. This systematic review and meta-analysis were conducted to identify the effect of metformin therapy on cognitive function in patients with diabetes.

Methods

Electronic databases (PubMed, EMBASE, PsycINFO, the Cochrane Library, and Web of Science) were systematically searched by two investigators from the date of inception until March 1, 2022. The study followed PRISMA guidelines. Inclusion criteria were defined according to the PECOSmodel. Eligible studies investigated cognitive dysfunction in metformin users compared with non-users in adults with diabetes. Only observational study designs (such as cohort, cross-section, and case-control) were included.

Results

A systematic search identified 1,839 articles, of which 28 (17 cohort, 8 case-control, and 3 cross-sectional studies) were included in the meta-analysis. Metformin reduced the occurrence of cognitive impairment in patients with diabetes [unadjusted hazard ratio (HR) = 0.67, 95% CI: 0.62–0.73; adjusted hazard ratio (aHR) = 0.92, 95% CI: 0.85–0.99]. In addition, the use of metformin was associated with a decreased risk of dementia (HR = 0.64, 95% CI: 0.59–0.69; aHR = 0.90, 95% CI: 0.84–0.96), while a random-effects meta-analysis indicated no significant effect of metformin on the risk of Alzheimer's disease (AD) (HR = 0.85, 95% CI: 0.60–1.22; aHR = 1.10, 95% CI: 0.95–1.28).

Conclusion

Metformin therapy decreased the occurrence risk of cognitive decline in patients with diabetes mellitus. Moreover, the use of metformin by adults with diabetes for the prevention of dementia, but not AD, is supported by the available evidence.
Associations of intermuscular adipose tissue and total muscle wasting score in PG-SGA with low muscle radiodensity and mass in nonmetastatic colorectal cancer: A two-center cohort study
Authors: Wang Yang , Wang Yuliuming , Li Guodong , Zhang Hao , Yu Hang , Xiang Jun , Wang Zitong , Jiang Xia , Yan Guoqing , Liu Yunxiao , Wang Chunlin , Xiong Huan , Wang Guiyu , Shi Hanping , Liu Ming
Published: August 2022

Backgrounds

The patient-generated subjective global assessment (PG-SGA) is one of the screening criteria for malnutrition, the skeletal muscle radiodensity (SMD) and skeletal muscle mass index (SMI) are associated with survival in colorectal cancer patients. Body composition parameters can be easily assessed; however, few studies have examined the association between total muscle wasting scores in PG-SGA and body composition parameters and two muscle abnormalities.

Methods

This cohort study included 1,637 stage I-III CRC patients from 2 clinical centers in China, who were enrolled in the training cohort (n = 1,005) and validation cohort (n = 632). Baseline data were collected prospectively from patients including age, BMI, staging, gait speed, hand grip strength (HGS), peak expiratory flow (PEF), neutrophil-lymphocyte ratio (NLR), intermuscular adipose tissue (IMAT), visceral fat area (VFA) and total muscle wasting score in PG-SGA. Relevant risk factors were subjected to logistic regression analysis and Cox regression analysis to identify characteristics associated with muscle abnormalities and survival. Based on the logistic model results, normograms were established to predict muscle abnormalities, and its discrimination and calibration were assessed using the receiver operating characteristic (ROC) curve and calibration curve. The Kaplan-Meier curves were used to assess the survival of colorectal cancer patients with malnutrition or sarcopenia in an inflammatory state (assessed by NLR).

Results

The mean age of all participants was 57.7 ± 10.6 years (56.9% males) and the prevalence of low SMD and low SMI was 32.2 and 39.5%, respectively. Low SMD rate was significantly associated with age, TNM stage, BMI, IMAT, walking speed, total muscle wasting score and NRS2002 score by logistic regression analysis (p < 0.05). Low SMI rate was significantly correlated with age, NLR, BMI, PEF, handgrip strength, calf circumference, walking speed, total muscle wasting score and NRS2002 score (p < 0.05). The AUCs of the diagnostic nomograms were 0.859 (95% CI, 0.831–0.886) for low SMD and 0.843 (95% CI, 0.813–0.871) for low SMI in the validation cohort. We also found that patients with colorectal cancer with malnutrition or sarcopenia had a worse prognosis when NLR ≥3.5.

Conclusion

Muscle abnormalities and malnutrition are strongly associated with mortality in patients with non-metastatic colorectal cancer. Early identification and intervention of the associated risk factors may offer new ways to improve patient prognosis.