bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel KCNT2 variant in a family with developmental and epileptic encephalopathies: a case report and literature review
Authors: Cui Fengji , Wulan Tuoya , Zhang Qian , Zhang Victor Wei , Jiang Yuhua 
Published: March 2024

Background: Developmental and epileptic encephalopathies (DEEs) are a group of heterogeneous neurodevelopmental diseases characterized mainly by developmental delay/intellectual disability and early-onset epilepsy. Researchers have identified variations in the KCNT2 gene (OMIM* 610044) as the cause of DEE type 57 (MIM# 617771).Case presentation: We report in this study a 46-year-old woman who presented with early-onset epilepsy, intellectual disability, hypertrichosis, coarse facial features, and short stature. Besides, there were four other affected individuals in her family history, including two elder brothers, a younger brother, and their mother. We collected blood samples from the proband, her two affected brothers, and her clinically normal daughter for genetic analysis. Clinical exome sequencing revealed a novel heterozygous variant in the KCNT2 gene (NM_198503: c.188G&gt;A, p.Arg63His) in the proband and her two affected brothers, while her daughter did not carry this variant. Furthermore, we reviewed all 25 patients identified in the literature with KCNT2 variants and compared their phenotypes.Conclusion: Epilepsy and intellectual disability/developmental delay occur in almost all patients with KCNT2 variants. KCNT2-relevant DEEs partially overlap with the clinical phenotypes of KATP channel diseases, particularly in hypertrichosis and distinctive coarse facial features.
Antibody dependent cellular cytotoxicity-inducing anti-EGFR antibodies as effective therapeutic option for cutaneous melanoma resistant to BRAF inhibitors
Authors: Muraro Elena , Montico Barbara , Lum Benedict , Colizzi Francesca , Giurato Giorgio , Salvati Annamaria , Guerrieri Roberto , Rizzo Aurora , Comaro Elisa , Canzonieri Vincenzo , Anichini Andrea , Del Vecchio Michele , Mortarini Roberta , Milione Massimo , Weisz Alessandro , Pizzichetta Maria Antonietta , Simpson Fiona , Dolcetti Riccardo , Fratta Elisabetta , Sigalotti Luca 
Published: March 2024

IntroductionAbout 50% of cutaneous melanoma (CM) patients present activating BRAF mutations that can be effectively targeted by BRAF inhibitors (BRAFi). However, 20% of CM patients exhibit intrinsic drug resistance to BRAFi, while most of the others develop adaptive resistance over time. The mechanisms involved in BRAFi resistance are disparate and globally seem to rewire the cellular signaling profile by up-regulating different receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR). RTKs inhibitors have not clearly demonstrated anti-tumor activity in BRAFi resistant models. To overcome this issue, we wondered whether the shared up-regulated RTK phenotype associated with BRAFi resistance could be exploited by using immune weapons as the antibody-dependent cell cytotoxicity (ADCC)-mediated effect of anti-RTKs antibodies, and kill tumor cells independently from the mechanistic roots.Methods and resultsBy using an in vitro model of BRAFi resistance, we detected increased membrane expression of EGFR, both at mRNA and protein level in 4 out of 9 BRAFi-resistant (VR) CM cultures as compared to their parental sensitive cells. Increased EGFR phosphorylation and AKT activation were observed in the VR CM cultures. EGFR signaling appeared dispensable for maintaining resistance, since small molecule-, antibody- and CRISPR-targeting of EGFR did not restore sensitivity of VR cells to BRAFi. Importantly, immune-targeting of EGFR by the anti-EGFR antibody cetuximab efficiently and specifically killed EGFR-expressing VR CM cells, both in vitro and in humanized mouse models in vivo, triggering ADCC by healthy donors’ and patients’ peripheral blood cells. ConclusionOur data demonstrate the efficacy of immune targeting of RTKs expressed by CM relapsing on BRAFi, providing the proof-of-concept supporting the assessment of anti-RTK antibodies in combination therapies in this setting. This strategy might be expected to concomitantly trigger the crosstalk of adaptive immune response leading to a complementing T cell immune rejection of tumors.
Case report: Rapid recovery after intrathecal rituximab administration in refractory anti-NMDA receptor encephalitis: report of two cases
Authors: Reda Mahasen , Jabbour Rosette , Haydar Asad , Jaafar Fatima , El Ayoubi Nabil , Nawfal Omar , Beydoun Ahmad 
Published: March 2024

BackgroundAnti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is one of the most prevalent etiologies of autoimmune encephalitis. Approximately 25% of anti-NMDAR encephalitis cases prove refractory to both first- and second-line treatments, posing a therapeutic dilemma due to the scarcity of evidence-based data for informed decision-making. Intravenous rituximab is commonly administered as a second-line agent; however, the efficacy of its intrathecal administration has rarely been reported.Case summaryWe report two cases of severe anti-NMDAR encephalitis refractory to conventional therapies. These patients presented with acute-onset psychosis progressing to a fulminant picture of encephalitis manifesting with seizures, dyskinesia, and dysautonomia refractory to early initiation of first- and second-line therapeutic agents. Both patients received 25 mg of rituximab administered intrathecally, repeated weekly for a total of four doses, with no reported adverse effects. Improvement began 2–3 days after the first intrathecal administration, leading to a dramatic recovery in clinical status and functional performance. At the last follow-up of 6 months, both patients remain in remission without the need for maintenance immunosuppression.ConclusionOur cases provide evidence supporting the intrathecal administration of rituximab as a therapeutic option for patients with refractory anti-NMDAR encephalitis. Considering the limited penetration of intravenous rituximab into the central nervous system, a plausible argument can be made favoring intrathecal administration as the preferred route or the simultaneous administration of intravenous and intrathecal rituximab. This proposition warrants thorough investigation in subsequent clinical trials.
Risk of adverse perinatal outcomes among women with clinical and subclinical histopathological chorioamnionitis
Authors: Olguín-Ortega Andrea , Figueroa-Damian Ricardo , Palafox-Vargas Martha Leticia , Reyes-Muñoz Enrique 
Published: March 2024

IntroductionHistologic chorioamnionitis (HCA) is a placental inflammatory condition associated with adverse perinatal outcomes (APOs). This historical cohort study explores the risk of APOs in pregnant women with HCA and compares the impact of clinical chorioamnionitis (CCA) with subclinical chorioamnionitis (SCCA).MethodologyPlacentas were evaluated by a perinatal pathologist tand all women with HCA were included. Two groups were integrated: (1) women with clinical chorioamnionitis (CCA) and (2) women with subclinical chorioamnionitis (SCCA). Additionally, we conducted a secondary analysis to compare the prevalence of APOs among stage 1, 2 and 3 of HCA and the risk of APOs between grades 1 and 2 of HCA. The APOs analyzed were preterm birth, stillbirth, neonatal weight &lt; 1,500 g, neonatal sepsis. Relative risk with 95% confidence interval was calculated.ResultsThe study included 41 cases of CCA and 270 cases of SCCA. The mean gestational age at diagnosis and birth was 30.2 ± 5.4 weeks and 32.5 ± 5.1 weeks, for group 1 and 2, respectively. The study also found that women with HCA stage 3 and grade 2 had a higher prevalence and risk of adverse perinatal outcomes.DiscussionThe findings of this study suggest the importance of placental histological study to excluded SCCA, which represents a significant risk to both maternal and neonatal health, contributing to high morbidity and mortality.
Antimicrobial treatment in invasive infections caused by Gordonia bronchialis: systematic review
Authors: Zivkovic Zaric Radica , Canovic Petar , Zaric Milan , Vuleta Marko , Vuleta Nedic Katarina , Jovanovic Jovan , Zornic Nenad , Nesic Jelena , Spasic Marko , Jakovljevic Stefan , Ilic Milena , Jovanovic Dalibor , Todorovic Zeljko , Arsenijevic Petar , Sovrlic Miroslav , Milovanovic Jasmina 
Published: March 2024

BackgroundCorynebacterium, Nocardia, Rhodococcus, Mycobacterium, as well as Gordonia genera belongs to the genus Gordonia, Actinomycetia class. Gordonia bronchialis is a nitrate-reducing, urease-producing, non-motile, force aerobe with a rod-like figure that is known to arrangement into sessile, cord-like groups. This systematic review aimed to establish whether and what invasive infections in humans were caused by Gordonia bronchialis, and to evaluate outcomes of administered antibiotic treatment.MethodsWe have registered this systematic review in PROSPERO database of systematic reviews and meta-analyses with the number CRD42022369974.ResultsA total of 24 publications were included (22 case reports and two case series) with 28 individual cases. The oldest patients had 92 years, and the youngest patients had 13 years. Clinical signs of infection were present in six patients (21%). All isolates were susceptible to ciprofloxacin, imipenem, and amikacin. Vancomycin was the most frequently used antibiotic with nine cases followed by ciprofloxacin, ceftriaxone, and amoxicillin/clavulanic acid.ConclusionAlthough there are no standardized recommendations to date, successful treatment with a favorable outcome has most often been carried out with fluoroquinolones, vancomycin with or without aminoglycosides, as well as carbapenems.
Spirometry test values can be estimated from a single chest radiograph
Authors: Yoshida Akifumi , Kai Chiharu , Futamura Hitoshi , Oochi Kunihiko , Kondo Satoshi , Sato Ikumi , Kasai Satoshi 
Published: March 2024

IntroductionPhysical measurements of expiratory flow volume and speed can be obtained using spirometry. These measurements have been used for the diagnosis and risk assessment of chronic obstructive pulmonary disease and play a crucial role in delivering early care. However, spirometry is not performed frequently in routine clinical practice, thereby hindering the early detection of pulmonary function impairment. Chest radiographs (CXRs), though acquired frequently, are not used to measure pulmonary functional information. This study aimed to evaluate whether spirometry parameters can be estimated accurately from single frontal CXR without image findings using deep learning.MethodsForced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC as spirometry measurements as well as the corresponding chest radiographs of 11,837 participants were used in this study. The data were randomly allocated to the training, validation, and evaluation datasets at an 8:1:1 ratio. A deep learning network was pretrained using ImageNet. The input and output information were CXRs and spirometry test values, respectively. The training and evaluation of the deep learning network were performed separately for each parameter. The mean absolute error rate (MAPE) and Pearson’s correlation coefficient (r) were used as the evaluation indices.ResultsThe MAPEs between the spirometry measurements and AI estimates for FVC, FEV1 and FEV1/FVC were 7.59% (r = 0.910), 9.06% (r = 0.879) and 5.21% (r = 0.522), respectively. A strong positive correlation was observed between the measured and predicted indices of FVC and FEV1. The average accuracy of &gt;90% was obtained in each estimation of spirometry indices. Bland–Altman analysis revealed good agreement between the estimated and measured values for FVC and FEV1.DiscussionFrontal CXRs contain information related to pulmonary function, and AI estimation performed using frontal CXRs without image findings could accurately estimate spirometry values. The network proposed for estimating pulmonary function in this study could serve as a recommendation for performing spirometry or as an alternative method, suggesting its utility.
Effects of secukinumab and ixekizumab on major adverse cardiovascular events in patients with psoriasis: a meta-analysis of randomized controlled trials
Authors: Zhang Yonghong , Yang Zhiya , Gong Jinyan , Shi Dongmei 
Published: March 2024

IntroductionThe aims of this study is to analyze the risk of major adverse cardiovascular events (MACEs) in patients with psoriasis treated with secukinumab and ixekizumab.MethodologyWe systematically identified randomized controlled trials (RCTs) that focused on the treatment of psoriasis with secukinumab and ixekizumab by conducting computerized searches of PubMed, Embase, and the Cochrane Library databases, spanning from their inception to October 31st, 2022. The search terms used included psoriasis, secukinumab, ixekizumab, and randomized controlled trial. Two independent evaluators conducted literature screening, data extraction, and assessed the quality of included studies based on predetermined inclusion and exclusion criteria. The gather data was subjected to meta-analysis using the statistical software RevMan 5.4.ResultsA total of 20 articles, encompassing 23 randomized controlled trials involving 10,746 psoriasis patients were included in the analysis. During the double-blind treatment period, the meta-analysis results indicated the following: There was no significant difference in the incidence of MACEs between the secukinumab and placebo groups [RR = 0.61, 95% CI (0.26, 1.44), p = 0.26]. Similarly, there was no significant difference in the incidence of MACEs with ixekizumab compared to the placebo group [RR = 0.47, 95% CI (0.15, 1.47), p = 0.20]. Furthermore, no significant difference in the incidence of MACEs was observed between secukinumab 300 mg and secukinumab 150 mg treatment groups [RR = 1.00, 95% CI (0.23, 4.35), p = 1.00]. Likewise, there was no significant difference in the incidence of MACEs between the ixekizumab Q4W (every 4 weeks) and ixekizumab Q2W (every 2 weeks) administration groups [RR = 4.01, 95% CI (0.45, 35.89), p = 0.21].ConclusionThe findings of this study suggest that neither secukinumab nor ixekizumab is significantly associated with the risk of MACEs in patients with psoriasis during double-blind treatment.Systematic review registration: Unique Identifier: CRD42022373756 https://www.crd.york.ac.uk/.
Integrated management of fruit trees and Bletilla striata: implications for soil nutrient profiles and microbial community structures
Authors: Xie Qiufeng , Xu Huimei , Wen Rouyuan , Wang Le , Yang Yan , Zhang Haizhu , Su BaoShun 
Published: March 2024

IntroductionForest medicinal compound systems in agroforestry ecosystems represent a multi-layered cultivation approach that utilizes forest resources efficiently. However, research on how these systems affect soil nutrients and microbial communities is limited.MethodsThis study compared the soil chemical properties and microbial communities of Bletilla striata (C) grown alone versus in agroforestry systems with apple (PB), pear (LB), and peach trees (TB), aiming to understand the impact of these systems on soil health and microbial diversity.ResultsSoil in the GAB systems showed increased levels of essential nutrients but lower pH and ammonium nitrogen levels compared to the control. Significant improvements in organic matter, total phosphorus, and total potassium were observed in TB, PB, and LB systems, respectively. The bacterial diversity increased in GAB systems, with significant changes in microbial phyla indicative of a healthier soil ecosystem. The correlation between soil properties and bacterial communities was stronger than with fungal communities.DiscussionIntegrating B. striata with fruit trees enhances soil nutrients and microbial diversity but may lead to soil acidification. Adjustments such as using controlled-release fertilizers and soil amendments like lime could mitigate negative impacts, improving soil health in GAB systems.
Effects of the catastrophic 2020 Yangtze River seasonal floods on microcystins and environmental conditions in Three Gorges Reservoir Area, China
Authors: Zhou Yuanhang , Wang Qilong , Xiao Guosheng , Zhang Zhi 
Published: March 2024

IntroductionDuring July and August 2020, Three Gorges Reservoir Area (TGRA) suffered from catastrophic seasonal floods. Floods changed environmental conditions and caused increase in concentration of microcystins (MCs) which is a common and potent cyanotoxin. However, the effects and seasonal variations of MCs, cyanobacteria, and environmental conditions in TGRA after the 2020 Yangtze River extreme seasonal floods remain largely unclear, and relevant studies are lacking in the literature.MethodsA total of 12 representative sampling sites were selected to perform concentration measurement of relevant water quality objectives and MCs in the representative area of the TGRA. The sampling period was from July 2020 to October 2021, which included the flood period. Organic membrane filters were used to perform the DNA extraction and analyses of the 16S rRNA microbiome sequencing data.ResultsResults showed the seasonal floods result in significant increases in the mean values of microcystin-RR (MCRR), microcystin-YR (MCYR), and microcystin-LR (MCLR) concentration and some water quality objectives (i.e., turbidity) in the hinterland of TGRA compared with that in non-flood periods (p &lt; 0.05). The mean values of some water quality objectives (i.e., total nitrogen (TN), total phosphorus (TP), total dissolved phosphorus (TDP), and turbidity), MC concentration (i.e., MCRR, MCYR, and MCLR), and cyanobacteria abundance (i.e., Cyanobium_PCC-6307 and Planktothrix_NIVA-CYA_15) displayed clear tendency of increasing in summer and autumn and decreasing in winter and spring in the hinterland of TGRA.DiscussionsThe results suggest that seasonal floods lead to changes in MC concentration and environmental conditions in the hinterland of TGRA. Moreover, the increase in temperature leads to changes in water quality objectives, which may cause water eutrophication. In turn, water eutrophication results in the increase in cyanobacteria abundance and MC concentration. In particular, the increased MC concentration may further contribute to adverse effects on human health.
Anosognosia is associated with increased prevalence and faster development of neuropsychiatric symptoms in mild cognitive impairment
Authors: Wang Sharon , Mimmack Kayden , Cacciamani Federica , Elnemais Fawzy Michael , Munro Catherine , Gatchel Jennifer , Marshall Gad A. , Gagliardi Geoffroy , Vannini Patrizia 
Published: March 2024

IntroductionBoth the loss of awareness for cognitive decline (a. k.a anosognosia) and neuropsychiatric symptoms (NPS) are common in patients with Alzheimer's disease (AD) dementia, even in prodromal stages, and may exacerbate functional impairment and negatively impact caregiver burden. Despite the high impact of these symptoms on patients and their caregivers, our knowledge of how they develop across the AD spectrum is limited. Here, we explored the cross-sectional and longitudinal associations between anosognosia and NPS in individuals with mild cognitive impairment (MCI).MethodsWe included 237 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) with a baseline clinical diagnosis of MCI. Everyday Cognition (ECog) questionnaire scores were used to measure complaints from participants and study-partners at baseline and annually over a mean of 4.29 years [standard deviation (SD) = 2.72]. Anosognosia was defined as the study-partner having an ECog score ≥2.5/4 and the participant having an ECog score &lt; 2.5/4 on their baseline measure and their last observation without more than two consecutive deviating observations during the follow-up period. The 12-item study-partner-rated Neuropsychiatric Inventory determined the presence or absence of specific NPS. Survival analyses were performed to analyze the frequency and temporal onset of NPS over time in individuals with and without anosognosia.ResultsThirty-eight out of 237 participants displayed anosognosia. Groups had similar lengths of follow-up at baseline (p &gt; 0.9), though participants with anosognosia had lower MMSE scores (p = 0.049) and a higher proportion of amyloid-positivity using PET (p &lt; 0.001. At baseline, the frequencies of agitation (p = 0.029) and disinhibition (p &lt; 0.001) were higher in the anosognosia group compared to the non-anosognosia group. Survival analyses showed earlier onset of seven of the 12 NPS in the anosognosia group (p's &lt; 0.001).DiscussionLoss of awareness for cognitive decline is associated with greater frequency and earlier onset of NPS over time in participants with MCI. These results support the hypothesis of a potential common underlying neurophysiological process for anosognosia and NPS, a finding that needs to be addressed in future studies.
The impact of stress on the behavior of C57BL/6 mice with liver injury: a comparative study
Authors: Mușat Mădălina Iuliana , Mitran Smaranda Ioana , Udriștoiu Ion , Albu Carmen Valeria , Cătălin Bogdan 
Published: March 2024

IntroductionDepressive-like behavior has been shown to be associated with liver damage. This study aimed to evaluate the impact of three different models of depression on the behavior of mice with liver injury.MethodsDuring the 4 weeks of methionine/choline deficiency diet (MCD), adult C57BL/6 mice were randomly divided into four groups: MCD (no stress protocol, n = 6), chronic unpredictable mild stress (CUMS, n = 9), acute and repeated forced swim stress [aFSS (n = 9) and rFSS (n = 9)].ResultsAll depression protocols induced increased anhedonia and anxiety-like behavior compared to baseline and had no impact on the severity of liver damage, according to ultrasonography. However, different protocols evoked different overall behavior patterns. After the depressive-like behavior induction protocols, animals subjected to aFSS did not exhibit anxiety-like behavior differences compared to MCD animals, while mice subjected to CUMS showed additional weight loss compared to FSS animals. All tested protocols for inducing depressive-like behavior decreased the short-term memory of mice with liver damage, as assessed by the novel object recognition test (NORT).DiscussionOur results show that the use of all protocols seems to generate different levels of anxiety-like behavior, but only the depressive-like behavior induction procedures associate additional anhedonia and memory impairment in mice with liver injury.