bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional identification of two novel variants and a hypomorphic variant in ASS1 from patients with Citrullinemia type I
Authors: Liu Jing , Wang Zhongjie , Yan Huiming , Teng Yanling , Shi Qingxin , Chen Jing , Tang Wanglan , Yu Wenxian , Peng Ying , Xi Hui , Ma Na , Liang Desheng , Li Zhuo , Wu Lingqian 
Published: July 2023

Background: Citrullinemia type I (CTLN1) is a rare autosomal recessive inborn error of the urea cycle caused by mutations in the gene encoding the arginosuccinate synthetase (ASS1) enzyme. Classic CTLN1 often manifests with acute hyperammonemia and neurological symptoms. Molecular genetic testing is critical for patient diagnosis.Methods: Three unrelated families with clinically suspected CTLN1 were included in this study. Potential pathogenic variants were identified using whole exome sequencing (WES) and validated using Sanger sequencing. Western blotting, quantitative PCR, immunofluorescent staining, and ELISA were used to assess functional changes in candidate ASS1 variants.Results: Five variants were identified, two of which were novel, and one has been reported, but its pathogenicity was not validated. The novel variant c.649-651del (p.P217del) and the 5′UTR variant (c.-4C&gt;T) resulted in a decrease in ASS1 expression at both the protein and transcription levels. The other novel variant, c.1048C&gt;T (p.Q350*), showed a marked decrease in expression at the protein level, with the formation of truncated proteins but an increased transcription. Both c.649_651del (p.P217del) and c.1048C&gt;T (p.Q350*) showed a highly significant reduction in enzyme activity, while c.-4C&gt;T had no effect.Conclusion: We identified two novel variants and a hypomorphic non-coding variant in ASS1 and validated the pathogenicity using functional studies. Our findings contribute to expanding the spectrum of ASS1 variants and understanding the genotype-phenotype relationships of CTLN1.
Efficacy and safety of Lenvatinib-based combination therapies for patients with unresectable hepatocellular carcinoma: a single center retrospective study
Authors: Huang Jian , Wang Zhen-Guang , Tao Qi-Fei , Yang Yun , Yuan Sheng-Xian , Gu Fang-Ming , Liu Hui , Pan Ze-Ya , Jiang Bei-Ge , Lau Wan Yee , Zhou Wei-Ping 
Published: July 2023

BackgroundReports on Lenvatinib-based therapies show promising treatment outcomes for patients with unresectable hepatocellular carcinoma (uHCC). However, the effect and safety of Lenvatinib-based therapies still need to be further studies.MethodsThis was a retrospective, single-center study on the safety and treatment efficacy of Lenvatinib-based combination therapies for uHCC Patients. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were progressive disease (PD), stable disease (SD), partial response (PR), and complete response (CR).ResultsOf 91 patients, there were 16 females and 75 males with uHCC who received systemic therapies based on Lenvatinib in our center. Forty-six patients (50.5%) received Lenvatinib combined with PD-1 antibody treatment. All these patients also received local therapy with the exception of 2 patients. The remaining 36 patinets received Lenvatinib combined with transcatheter arterial chemoembolization (TACE), 1 patient treated Lenvatinib combined with radiotherapy, 8 patients received Lenvatinib alone. At a median treatment time of 8 months, the objective response rate (ORR) of the entire cohort was 58.2% (53 patients), including 7 patients with CR and 46 patients with PR. 21 patients (23.1%) had SD. The disease control rate (DCR) of all patients was 81.3% (74 patients). However, 17 patients (18.7%) developed PD. The 1- and 2-year cumulative OS rates for the entire cohort were 66.8% and 39.3%, while the corresponding PFS rates were 38.0% and 17.1%, respectively. Univariate and multivariate Cox regression analysis revealed multiple tumor sites to be an independent OS risk factor for uHCC patients (HR=2.204, 95% CI=1.104-4.399, P=0.025). The most frequently reported adverse events in all patients were AST elevation (51.6%), followed by hypertension (33.0%), ALT elevation (26.4%), and decreased appetite (25.3%). After a combination treatment of Lenvatinib-based therapies, 15 patients met the criteria for salvage liver resection and underwent down-staging hepatectomy with a curative intent. The combination of PD-1 treatment was not very effective in improving the prognosis of uHCC patients treated with Lenvatinib combined with TACE.ConclusionOur study demonstrated that a proportive of patients benefited from Lenvatinib-based combination therapies with manageable safety profiles, allowing these patients to undergo downstaging surgery with curative intent.
Dimethyl fumarate-related immune and transcriptional signature is associated with clinical response in multiple sclerosis-treated patients
Authors: Sánchez-Sanz Alicia , García-Martín Santiago , Sabín-Muñoz Julia , Moreno-Torres Irene , Elvira Víctor , Al-Shahrour Fátima , García-Grande Aranzazu , Ramil Elvira , Rodríguez-De la Fuente Ofir , Brea-Álvarez Beatriz , García-Hernández Ruth , García-Merino Antonio , Sánchez-López Antonio José 
Published: July 2023

Background and objectiveDimethyl fumarate (DMF) is an immunomodulatory drug approved for the therapy of multiple sclerosis (MS). The identification of response biomarkers to DMF is a necessity in the clinical practice. With this aim, we studied the immunophenotypic and transcriptomic changes produced by DMF in peripheral blood mononuclear cells (PBMCs) and its association with clinical response.Material and methodsPBMCs were obtained from 22 RRMS patients at baseline and 12 months of DMF treatment. Lymphocyte and monocyte subsets, and gene expression were assessed by flow cytometry and next-generation RNA sequencing, respectively. Clinical response was evaluated using the composite measure “no evidence of disease activity” NEDA-3 or “evidence of disease activity” EDA-3 at 2 years, classifying patients into responders (n=15) or non-responders (n=7), respectively.ResultsIn the whole cohort, DMF produced a decrease in effector (TEM) and central (TCM) memory T cells in both the CD4+ and CD8+ compartments, followed by an increase in CD4+ naïve T cells. Responder patients presented a greater decrease in TEM lymphocytes. In addition, responder patients showed an increase in NK cells and were resistant to the decrease in the intermediate monocytes shown by non-responders. Responder patients also presented differences in 3 subpopulations (NK bright, NK dim and CD8 TCM) at baseline and 4 subpopulations (intermediate monocytes, regulatory T cells, CD4 TCM and CD4 TEMRA) at 12 months. DMF induced a mild transcriptional effect, with only 328 differentially expressed genes (DEGs) after 12 months of treatment. The overall effect was a downregulation of pro-inflammatory genes, chemokines, and activators of the NF-kB pathway. At baseline, no DEGs were found between responders and non-responders. During DMF treatment a differential transcriptomic response was observed, with responders presenting a higher number of DEGs (902 genes) compared to non-responders (189 genes).ConclusionsResponder patients to DMF exhibit differences in monocyte and lymphocyte subpopulations and a distinguishable transcriptomic response compared to non-responders that should be further studied for the validation of biomarkers of treatment response to DMF.
Type and duration of water stress influence host selection and colonization by exotic ambrosia beetles (Coleoptera: Curculionidae)
Authors: Ranger Christopher M. , Parajuli Madhav , Gresham Sean , Barnett Jenny , Villani Sara , Walgenbach James , Baysal-Gurel Fulya , Owen James S. , Reding Michael E. 
Published: July 2023

Fungus-farming ambrosia beetles in the tribe Xyleborini tunnel into plants and trees to establish chambers for cultivating their nutritional fungal mutualists and rearing offspring. Some xyleborine ambrosia beetles preferentially infest and perform better in living but weakened trees. Flood stress predisposes horticultural tree crops to infestation, but the impact of drought stress has not been well studied. Our objectives were to compare the effects of flood stress vs. drought stress on host selection and colonization by xyleborine ambrosia beetles and to assess the duration of flooding. Container-grown Cornus florida L. trees were flood stressed using a pot-in-pot system to submerge the roots in water while drought-stressed conditions were imposed by withholding irrigation and precipitation. When experimental trees were held under field conditions for 14 days, 7.5 × more ambrosia beetles landed on stems of the flood-stressed than on the drought-stressed trees. During two additional experiments over 14 and 22 days, ambrosia beetles tunneled into the flood-stressed trees but not the drought-stressed or standard irrigation trees. By simultaneously deploying trees that were flood stressed for varying lengths of time, it was found that more tunnel entrances, and xyleborine adults and offspring were recovered from trees that were flooded for 1–16 days and 7–22 days than from trees that were flooded for 14–29 days and 28–43 days. These results indicate that acute and severe drought stress does not predispose C. florida to infestation, but flood stress and the duration of flooding influence ambrosia beetle host selection and colonization. Understanding the role of host quality on ambrosia beetle preference behavior will assist with predicting the risk of infestation of these opportunistic insects in horticultural tree crops.
Comparison of different therapeutic approaches for pulmonary cryptococcosis in kidney transplant recipients: a 15-year retrospective analysis
Authors: Chen Shuyang , Yu Guoqing , Chen Meiyan , You Yanjing , Gu Lei , Wang Qing , Wang Huijuan , Lai Guoxiang , Yu Zongyang , Wen Wen 
Published: July 2023

IntroductionOrgan transplant recipients are at increased risk of developing pulmonary cryptococcosis (PC) due to weakened cell-mediated immunity caused by immunosuppressors. However, the nonspecific symptoms associated with PC can often lead to misdiagnosis and inappropriate treatment.MethodsWe conducted a retrospective analysis of data from 23 kidney transplant recipients with PC between April 2006 to January 2021.ResultsThe median time from transplantation to the diagnosis of pathology-proven PC 4.09  years. Seventeen patients presented respiratory symptoms, including sputum-producing cough and dyspnea. Additionally, three patients also developed central nervous system (CNS) infections. Chest CT scans frequently revealed nodule-shaped lesions, which can mimic lung carcinoma. Serological tests did not demonstrate any specific changes. Nine patients received surgical resection as treatment. Fourteen patients were treated with antifungal medication only. No recurrence was observed in all 23 patients.ConclusionOur study suggests that fever and sputum-producing cough are common symptoms of PC, and cryptococcal meningitis should not be excluded if corresponding symptoms occur. Fluconazole is a common and effective antifungal agent. Surgical resection should be considered for patients who do not respond well to antifungal therapy. Clinicians should be aware of these findings when evaluating transplant recipients with respiratory symptoms.
Emotion regulation strategies and the two-dimensional model of adult attachment: a pilot study
Authors: Domic-Siede Marcos , Guzmán-González Mónica , Burgos Josefa , Carvallo Catalina , Flores-Guerra Camila , Fredes-Valenzuela Constanza , Suazo Javiera , Véliz-García Oscar , Calderón Carlos , Sánchez-Corzo Andrea , Perrone-Bertolotti Marcela , Marín-Medina Jennifer 
Published: July 2023

IntroductionEmotion Regulation plays a crucial role in human’s daily lives. Extensive research has shown that people with different attachment orientations exhibit divergencies in how they perform emotion regulation strategies.Methods44 adults performed an experimental emotion regulation task in which they were instructed to attend, reappraise, or suppress their emotions while viewing negative and neutral images taken from the International Affective Picture System (IAPS). Afterward, participants rated valence, arousal, and emotional dominance elicited by the images. Additionally, attachment orientations were measured using the ECR-12 questionnaire.ResultsResults showed a relationship between attachment avoidance and the level of arousal during the reappraisal condition; specifically, the higher attachment avoidance levels, the greater the emotional intensity during the implementation of cognitive reappraisal strategy. Such results suggest an association between failing in downregulate intense emotions using cognitive reappraisal when there are higher levels of attachment avoidance. Consistently, we also found that lower dominance during reappraisal was associated with more levels of avoidance.ConclusionThese results indicate that people with higher levels of attachment avoidance experience difficulties when using the cognitive reappraisal strategy to reduce the emotional impact produced by negative emotional stimuli. Our findings reinforce the idea that avoidant people experience high physiological activation when experience emotions.
Predictive factors and clinicopathological characteristics of outcome in poorly differentiated thyroid carcinoma: a single-institution study
Authors: Wan Zheng , Wang Bing , Yao Jing , Li Qing , Miao Xin , Jian Yanbing , Huang Sisi , Lai Shengwei , Li Chen , Tian Wen 
Published: July 2023

ObjectiveTo elucidate the clinicopathological characteristics and prognostic factors of poorly differentiated thyroid carcinoma.MethodA total of 24912 thyroid carcinoma patients admitted to the First Medical Center of Chinese People’s Liberation Army General Hospital from 2005 to 2020 were retrospectively reviewed. A total of 94 patients (39 males and 55 females, a male-female ratio of 1:1.4) fulfilled the selection criteria. Of these, 73 patients had undergone surgery. The clinical and pathological data were collected from each enrolled patient. Univariate and multivariate Cox regression analyses were performed to determine independent prognostic factors. All analyses were performed with the SPSS version 26.0 and R version 1.2.5033 in the R Studio environment.ResultsThe specimens included 20 cases of poorly differentiated thyroid carcinoma complicated with papillary thyroid carcinoma, 17 cases complicated with follicular thyroid carcinoma, 34 cases complicated with other pathological types and 23 with a separate entity. The patient demonstrated a large age span, median age was 57 years (range 8–85 years, average 55.20 ± 15.74 years). The survival time of the 94 cases was calculated, and the mean Overall survival time was 33 (range, 1-170) months, and the mean Recurrence-free survival time was 14 (range, 1-90) months. Recurrence-free mortality is related to the age at diagnosis, extrathyroidal extension and Associated thyroid cancer (p&lt;0.05). In contrast, overall mortality is related to the age at diagnosis, sex, extrathyroidal extension, T stage (AJCC 8th), surgery and radiation (p&lt;0.05).ConclusionMiddle-aged and elderly patients are still at high risk for poorly differentiated thyroid carcinoma. The pathologic results of poorly differentiated thyroid carcinoma are varied, and reasonable treatment has an important impact on the prognosis of poorly differentiated thyroid carcinoma.
Common practice patterns in the diagnosis and management of Vogt–Koyanagi–Harada syndrome: a survey study of uveitis specialists
Authors: Choo Charlene H. , Acharya Nisha R. , Shantha Jessica G. 
Published: July 2023

IntroductionVogt–Koyanagi–Harada (VKH) syndrome is an inflammatory condition characterized by bilateral, granulomatous panuveitis with or without systemic manifestations, and accounts for up to 18% of referrals for panuveitis at tertiary centers in the United States of America. Despite ongoing research, there is limited evidence and no clear consensus on how to diagnose and treat patients with VKH, leading to variations in practice patterns among uveitis specialists.MethodsAn anonymous, online survey was distributed to uveitis specialists in the American Uveitis Society (AUS). The survey included 21 questions that asked for non-identifiable demographics and covered topics such as preferred imaging modalities, treatment for the first episode of VKH, and perceived efficacy of immunomodulatory therapy (IMT).ResultsA total of 104 surveys were included for analysis, representing a 38.4% response rate from the AUS listserv. A majority of respondents were uveitis fellowship trained and practiced in North America in an academic setting. Fluorescein angiography and enhanced depth imaging with optical coherence tomography were rated as the most consistently useful methods for the diagnosis of VKH. For treatment of acute initial-onset VKH, responses were divided between a preference for high-dose systemic corticosteroids with IMT (61.5%) and without IMT (37.5%). Methotrexate and mycophenolate mofetil were the most common IMTs to be used as first-line therapies, but adalimumab and infliximab were perceived to be the most effective for the treatment for VKH.DiscussionWhile there are some common trends in the practice patterns for the diagnosis and treatment of patients with VKH, there was no clear consensus on the topic of IMT. There was a slight preference among uveitis specialists to use both IMT and systemic corticosteroids for the first episode of acute VKH.
Rapamycin treatment induces tubular proteinuria: role of megalin-mediated protein reabsorption
Authors: Peres Rodrigo A. S. , Peruchetti Diogo B. , Silva-Aguiar Rodrigo P. , Teixeira Douglas E. , Gomes Carlos P. , Takiya Christina M. , Pinheiro Ana Acacia S. , Caruso-Neves Celso 
Published: July 2023

Introduction: Rapamycin is an immunosuppressor that acts by inhibiting the serine/threonine kinase mechanistic target of rapamycin complex 1. Therapeutic use of rapamycin is limited by its adverse effects. Proteinuria is an important marker of kidney damage and a risk factor for kidney diseases progression and has been reported in patients and animal models treated with rapamycin. However, the mechanism underlying proteinuria induced by rapamycin is still an open matter. In this work, we investigated the effects of rapamycin on parameters of renal function and structure and on protein handling by proximal tubule epithelial cells (PTECs).Methods: Healthy BALB/c mice were treated with 1.5 mg/kg rapamycin by oral gavage for 1, 3, or 7 days. At the end of each treatment, the animals were kept in metabolic cages and renal function and structural parameters were analyzed. LLC-PK1 cell line was used as a model of PTECs to test specific effect of rapamycin.Results: Rapamycin treatment did not change parameters of glomerular structure and function. Conversely, there was a transient increase in 24-h proteinuria, urinary protein to creatinine ratio (UPCr), and albuminuria in the groups treated with rapamycin. In accordance with these findings, rapamycin treatment decreased albumin-fluorescein isothiocyanate uptake in the renal cortex. This effect was associated with reduced brush border expression and impaired subcellular distribution of megalin in PTECs. The effect of rapamycin seems to be specific for albumin endocytosis machinery because it did not modify renal sodium handling or (Na++K+)ATPase activity in BALB/c mice and in the LLC-PK1 cell line. A positive Pearson correlation was found between megalin expression and albumin uptake while an inverse correlation was shown between albumin uptake and UPCr or 24-h proteinuria. Despite its effect on albumin handling in PTECs, rapamycin treatment did not induce tubular injury measured by interstitial space and collagen deposition.Conclusion: These findings suggest that proteinuria induced by rapamycin could have a tubular rather than a glomerular origin. This effect involves a specific change in protein endocytosis machinery. Our results open new perspectives on understanding the undesired effect of proteinuria generated by rapamycin.
Assessment of physical activity among adolescents: a guide to the literature
Authors: Sedlačík Marek , Lacinová Veronika , Hasilová Kamila 
Published: July 2023

PurposeThe aim of this article is to systematically review articles and annual reports concerning young peoples' physical activity (PA) and linking this to considerations of the state and national defense.MethodA systematic search of the literature included an analysis of publications accessible in global databases and other available books, student papers, and projects. The articles and reports were categorized based on year of publication, methods used, age of respondents, sample size, country, and digital object identifier (DOI).ResultsThe result of this search is an overview of the extent and manner in which the worldwide scientific community is addressing the current situation and the long-term development of the physical fitness of adolescents. This publication also maps to what extent professional publications and articles are addressing PA from the perspective of the needs of armies and armed forces of various countries around the world.ConclusionsThe article provides a systematic overview of methods used to measure PA, and an overview of articles dealing with assessing PA. The examined articles indicate that from the perspective of not only national defense, but also health and overall quality of life, in particular, we need initiatives to encourage and motivate young people to increase their everyday PA. The research therefore also includes an overview of factors that may considerably influence PA. The results ascertained in this publication will be used, i.a. for investigating a longitudinal defense research project of the Ministry of Defense of the Czech Republic in which the authors are participating.
Attention deficit hyperactivity disorder is associated with (a)symmetric tonic neck primitive reflexes: a systematic review and meta-analysis
Authors: Wang Meng , Yu Jing , Kim Hyun-Duck , Cruz Angelita Bautista 
Published: July 2023

IntroductionInvestigation on the association between attention deficit hyperactivity disorder (ADHD) and primary reflexes is in the initial stage, with considerable differences in the findings. This study evaluated the association between ADHD and primitive reflexes using systematic review and meta-analysis.MethodsData were obtained from PubMed, Cochrane Library, Web of Science, EBSCO (Medical Literature Analysis and Retrieval System Online, American Psychological Association Psyclnfo, and Education Resources Information Center), Embase, Scopus, and ProQuest. Articles were searched from the date of inception of the respective databases to January 01, 2023, and StataCorp Stata (version 15) was used for the analysis.ResultsFour articles with 229 samples were included in the meta-analysis. Results showed a significant positive and moderate correlation between ADHD and primitive reflexes, particularly asymmetric tonic neck reflex: summary r value = 0.48, 95% CI = 0.27–0.64; symmetric tonic neck reflex: summary r value = 0.39, 95% CI = 0.25–0.52. Overall, findings from the sub-group analysis indicate that the behavioral problem measuring tool (Conners’ scale), sex, and primitive reflex test could significantly moderate the relationships between ADHD and ATNR and STNR primitive reflexes.ConclusionADHD symptoms in children are closely related to the non-integration of (a)symmetric tonic neck primitive reflexes. Longitudinal or experimental studies should be conducted to reveal the causal relationship between ADHD and primitive reflexes in the future.