bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: The compound heterozygotes variants in FLT4 causes autosomal recessive hereditary lymphedema in a Chinese family
Authors: Xiang Qinqin , Chen Jing , Xiao Xiao , Xu Bocheng , Xie Hanbing , Wang He , Yang Mei , Liu Shanling 
Published: March 2023

Background: Lymphedema is a local form of tissue swelling, which is caused by excessive retention of lymph fluid in interstitial compartment caused by impaired lymphatic drainage damage. Primary lymphedema is caused by developmental lymphatic vascular abnormalities. Most cases are inherited as autosomal dominant, with incomplete penetrance and variable expression. Here we report compound heterozygotes variants in FLT4 of a Chinese family associated with primary lymphedema display autosomal recessive inheritance.Case presentation: Trio-whole-exome sequencing (Trio-WES) was performanced to analyse the underlying genetic cause of a proband with primary lymphedema in a Chinese family. Sanger sequencing was used to validate the variants in proband with primary lymphedema and members of the family with no clinical signs and symptoms. We reported compound heterozygotes for the Fms Related Receptor Tyrosine Kinase 4 (FLT4) gene detected in the proband, who carrying two different point variants. One was a missense variant (NM_182925.5; c.1504G&gt;A, p.Glu502Lys), and the other was a recurrent variant (NM_182925.5; c.3323_3325del, p.Phe1108del). The missense variant c.1504G&gt;A was detected in the proband, unaffected father, and unaffected paternal grandmother but not detected in unaffected paternal grandfather. The recurrent variant c.3323_3325del was detected in the proband, unaffected mother, and unaffected maternal grandfather but not detected in unaffected maternal grandmother. Our results suggests the possibility of an autosomal recessive inherited form of primary lymphedema resulting from variants of FLT4 encoding the vascular endothelial growth factor receptor-3.Conclusion: The results of the present study identifed compound heterozygotes FLT4 variants in a family with primary lymphedema which provides more information for autosomal recessive primary lymphedema caused by FLT4.
Newly detected, virulent Toxoplasma gondii COUG strain causing fatal steatitis and toxoplasmosis in southern sea otters (Enhydra lutris nereis)
Authors: Miller Melissa Ann , Newberry Cara A. , Sinnott Devinn M. , Batac Francesca Irene , Greenwald Katherine , Reed Angelina , Young Colleen , Harris Michael D. , Packham Andrea E. , Shapiro Karen 
Published: March 2023

From February 2020 to March 2022, four southern sea otters (Enhydra lutris nereis) stranded in California with severe protozoal steatitis and systemic toxoplasmosis. Three of the infected otters stranded within 26 km of each other, and all four animals died during periods of increased rainfall-driven surface water runoff. High parasite burdens were observed in all tissues except the central nervous system, and toxoplasmosis with severe protozoal steatitis was the primary cause of death for all cases. This lesion pattern differs substantially from all prior reports of toxoplasmosis in sea otters. All cases were T. gondii-positive via serology, immunohistochemistry, and PCR. Multilocus sequence typing at 13 loci revealed that all were infected with the same strain of T. gondii, previously characterized as an atypical and rare genotype in North America (TgCgCa1, or COUG). The COUG genotype was first isolated from mountain lions in British Columbia, Canada during investigation of a waterborne outbreak of toxoplasmosis in humans. This genotype has not been previously reported from sea otters, nor any aquatic species. All prior T. gondii strains obtained from &gt;140 southern sea otters represent Type II or Type X strains, or variants of these genotypes. Archival necropsy data (&gt;1,000 animals over 24 years) were negative for prior cases of severe T. gondii-associated steatitis prior to the cases described herein, and no sublethal COUG T. gondii infections have been previously indentified in sea otters. According to prior studies, the T. gondii COUG genotype is highly virulent in mice and is unusual among T. gondii isolates in eliciting a Type I interferon response in murine and human cells in vitro; this unusual immunomodulatory response could explain the apparent high virulence of this atypical T. gondii strain. Our findings reveal a novel and concerning lesion pattern for sea otters with toxoplasmosis. Due to high zoonotic potential and the risk of infection via shared marine food resources, these findings may also indicate potential health threats for other animals and humans.
Transcriptome analysis of Lr19-virulent mutants provides clues for the AvrLr19 of Puccinia triticina
Authors: Cui Zhongchi , Wu Wenyue , Fan Fan , Wang Fei , Liu Daqun , Di Dianping , Wang Haiyan 
Published: March 2023

IntroductionWheat leaf rust caused by Puccinia triticina (Pt) remains one of the most destructive diseases of common wheat worldwide. Understanding the pathogenicity mechanisms of Pt is important to control wheat leaf rust.MethodsThe urediniospores of Pt race PHNT (wheat leaf rust resistance gene Lr19-avirulent isolate) were mutagenized with ethyl methanesulfonate (EMS), and two Lr19-virulent mutants named M1 and M2 were isolated. RNA sequencing was performed on samples collected from wheat cultivars Chinese Spring and TcLr19 infected with wild-type (WT) PHNT, M1, and M2 isolates at 14 days post-inoculation (dpi), respectively. Screening AvrLr19 candidates by quantitative reverse transcription PCR (qPCR) and Agrobacterium-mediated transient assays in Nicotiana benthamiana.Results560 genes with single nucleotide polymorphisms (SNPs) and insertions or deletions (Indels) from non-differentially expressed genes were identified. Among them, 10 secreted proteins were screened based on their fragments per kilobase of exon model per million mapped reads (FPKM) values in the database. qPCR results showed that the expression profiles of 7 secreted proteins including PTTG_27471, PTTG_12441, PTTG_28324, PTTG_26499, PTTG_06910, PTTG_26516, and PTTG_03570 among 10 secreted proteins in mutants were significantly different with that in wild-type isolate after infection wheat TcLr19 and might be related to the recognition between Lr19 and AvrLr19. In addition, a total of 216 differentially expressed genes (DEGs) were obtained from three different sample comparisons including M1-vs-WT, M2-vs-WT, and M1-vs-M2. Among 216 DEGs, 15 were predicted to be secreted proteins. One secreted protein named PTTG_04779 could inhibit programmed progress of cell death (PCD) induced by apoptosis-controlling genes B-cell lymphoma-2 associated X protein (BAX) on Nicotiana benthamiana, indicating that it might play a virulence function in plant. Taken together, total 8 secreted proteins, PTTG_04779, PTTG_27471, PTTG_12441, PTTG_28324, PTTG_26499, PTTG_06910, PTTG_26516, PTTG_03570 are identified as AvrLr19 candidates.DiscussionOur results showed that a large number of genes participate in the interaction between Pt and TcLr19, which will provide valuable resources for the identification of AvrLr19 candidates and pathogenesis-related genes.
Characterization of cephalosporin and fluoroquinolone resistant Enterobacterales from Irish farm waste by whole genome sequencing
Authors: Prendergast Deirdre M. , Slowey Rosemarie , Burgess Catherine M. , Murphy Declan , Johnston Dayle , Morris Dearbháile , O’ Doherty Áine , Moriarty John , Gutierrez Montserrat 
Published: March 2023

BackgroundThe Enterobacterales are a group of Gram-negative bacteria frequently exhibiting extended antimicrobial resistance (AMR) and involved in the transmission of resistance genes to other bacterial species present in the same environment. Due to their impact on human health and the paucity of new antibiotics, the World Health Organization (WHO) categorized carbapenem resistant and ESBL-producing as critical. Enterobacterales are ubiquitous and the role of the environment in the transmission of AMR organisms or antimicrobial resistance genes (ARGs) must be examined in tackling AMR in both humans and animals under the one health approach. Animal manure is recognized as an important source of AMR bacteria entering the environment, in which resistant genes can accumulate.MethodsTo gain a better understanding of the dissemination of third generation cephalosporin and fluoroquinolone resistance genes between isolates in the environment, we applied whole genome sequencing (WGS) to Enterobacterales (79 E. coli, 1 Enterobacter cloacae, 1 Klebsiella pneumoniae, and 1 Citrobacter gillenii) isolated from farm effluents in Ireland before (n = 72) and after (n = 10) treatment by integrated constructed wetlands (ICWs). DNA was extracted using the MagNA Pure 96 system (Roche Diagnostics, Rotkreuz, Switzerland) followed by WGS on a MiSeq platform (Illumina, Eindhoven, Netherlands) using v3 chemistry as 300-cycle paired-end runs. AMR genes and point mutations were identified and compared to the phenotypic results for better understanding of the mechanisms of resistance and resistance transmission.ResultsA wide variety of cephalosporin and fluoroquinolone resistance genes (mobile genetic elements (MGEs) and chromosomal mutations) were identified among isolates that mostly explained the phenotypic AMR patterns. A total of 31 plasmid replicon types were identified among the 82 isolates, with a subset of them (n = 24), identified in E. coli isolates. Five plasmid replicons were confined to the Enterobacter cloacae isolate and two were confined to the Klebsiella pneumoniae isolate. Virulence genes associated with functions including stress, survival, regulation, iron uptake secretion systems, invasion, adherence and toxin production were identified.ConclusionOur study showed that antimicrobial resistant organisms (AROs) can persist even following wastewater treatment and could transmit AMR of clinical relevance to the environment and ultimately pose a risk to human or animal health.
Multimodality liver directed treatment for colorectal liver metastasis: Array of complementary options can improve outcomes - A single centre experience from India
Authors: Patkar Shraddha , Chopde Amit , Shetty Nitin , Kulkarni Suyash , Gala Kunal Bharat , Chandra Daksh , Ramaswamy Anant , Ostwal Vikas , Goel Mahesh 
Published: March 2023

AIMComplimentary use of Liver directed therapies (LDTs) with systemic chemotherapy has improved oncologic outcomes in colorectal liver metastasis (CRLM). We analysed institutional results of multimodality management.MethodsRetrospective analysis of prospectively maintained database of CRLM patients managed with LDT including surgical resection, Ablation, Transarterial chemoembolization (TACE) or Transarterial radioembolization (TARE) between November 2011 to March 2020. Management plan was decided in multidisciplinary meeting. Resectable tumours underwent surgical resection or ablation or both in some cases. Borderline resectable or unresectable disease was treated with down staging chemotherapy or TACE/TARE followed by resection or ablation. All patients received adjuvant chemotherapy. Factors influencing survival were analysed.ResultsOut of total 375 patients, surgery alone was done in 191 (50.93%) patients while surgery with other LDT in 26 patients (6.93%). Ablation alone was done in 100 (26.66%) whereas TACE/TARE were done as standalone treatment in 21 (5.6%) and 7 (1.86%) patients respectively. TACE + ablation was done in 28 (7.46%) and TARE + ablation was done in 2(0.53%) patients.5-year Overall Survival(OS) was 49.8% while Event free survival(EFS) was 21.4%. The median OS and EFS for surgical group was significantly better than non-surgical group (78 V/s 39 months; p&lt;0.05 and 20 V/s 15 months p &lt;0.005). The resectable (78 months) group had better median OS as compared to borderline resectable and Unresectable group (39 months and 29 months). Male gender, resectable disease and surgical intervention were associated with improved OS.ConclusionAlthough surgery remains the mainstay of treatment, complementary use of non-surgical LDT with systemic therapy offers possibility of good outcomes in advanced liver limited disease. Our experience highlights the impact of multidisciplinary care in optimizing CRLM treatment.
Risk factors of temperature increase after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy
Authors: Kang Hui-xia , Ma Jun-ying , Su Yan-yan , Kang Shan , Feng Bao-jie , Feng Xiao-bei , Wang Xu-sha , Lu Yun-yun 
Published: March 2023

BackgroundCytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the standard treatment for patients with peritoneal cancer (PC). Following CRS-HIPEC, patients may also face risks caused by whole body hyperthermia. This study analyzed the incidence of temperature increases following CRS-HIPEC and identified the attendant risk factors.MethodsA retrospective analysis was carried out among 458 patients who received CRS-HIPEC at the Fourth Hospital of Hebei Medical University between August 2018 and January 2021. The patients were divided into two groups according to post-HIPEC axillary temperature (≥38°C), with the demographics and the laboratory test results subsequently analyzed and compared, and the risk factors pertaining to temperature increases analyzed using univariate and multivariate logistic regression.ResultsDuring CRS-HIPEC, 32.5% (149/458) of the patients with a temperature increase had an axillary temperature of not lower than 38°C, and 8.5% (39/458) of the patients with hyperpyrexia had an axillary temperature of not lower than 39°C. Female gender, gynecological malignancies, type of chemotherapy drug, increased postoperative neutrophil percentage, and a sharp drop in postoperative prealbumin were associated with the incidence of a temperature increase and axillary temperatures of &gt;38°C. Among these factors, the type of chemotherapy drug was identified as an independent risk factor for a temperature increase during CRS-HIPEC.ConclusionBy determining the risk factors pertaining to temperature increases during CRS-HIPEC, medical staff can identify the attendant risks among the patients and thus take preventive measures in a timely manner to maintain the patient’s body temperature at a stable level. This suggests that further clinical research should be conducted to build a risk-prediction model for temperature increases following CRS-HIPEC.
Metabolic power and energy expenditure in the German Bundesliga
Authors: Venzke Jan , Weber Hendrik , Schlipsing Marc , Salmen Jan , Platen Petra 
Published: March 2023

The aims of the study were to analyze metabolic power (MP) and MP derived parameters for different positions in the German Soccer Bundesliga and to evaluate if classification of high-intensity is more suited using the metabolic power approach instead of using traditional speed-based methods. 1,345 video match analysis (25 Hz) datasets from 380 players in 96 matches of the German first Bundesliga were gathered by an automatic player tracking system. Displacement (speed, acceleration, distance) and energetic (MP, energy expenditure) variables were determined. Intensity was classified utilizing conventional thresholds. Metabolic and running profiles were compared among six positional groups and between the halves of the match respectively (one-way ANOVA). Further, time spent, distance covered and energy expended at high speed (&gt;15.5 km h−1) and high acceleration (&gt;2 m s−2) were compared to those at high MP (&gt;20 W kg−1) (one-way ANOVA) for evaluating if metabolic power is more suited to describe intensity in team sports. Main findings are that central-attacking midfielders (CAM) and central midfielders (CM) expended more energy (CAM: 59.8 ± 4.2 kJ kg−1; CM: 59.6 ± 3.6 kJ kg−1) and covered more distance (CAM: 11,494 ± 765 m; CM: 11,445 ± 638 m) than all other positions (p &lt; 0.001). In the whole group of players, less time (t) and less energy were expended (EE) in high speed (t: 302 ± 84 s; EE: 10.1 ± 2.9 kJ kg−1) and at high acceleration zones (t: 147 ± 24 s; EE: 5.5 ± 1.2 kJ kg−1) when compared to high MP zone (t: 617 ± 141 s; EE: 20.0 ± 4.4 kJ kg−1) (p &lt; 0.001). Furthermore, players covered more distance at high MP (2,464 ± 597 m) than at high speed (1,638 ± 458 m) and much less at high acceleration (359 ± 67 m) (p &lt; 0.001). The higher activity profiles of CAM and CM compared to the other positions indicate the need for higher developed physiological performance in players of these positions. High intensity activities should be interpreted differently when using MP and displacement parameters as indicators of high intensity in soccer.
Barriers and facilitators for smoking cessation in chronic smokers with atherosclerotic cardiovascular disease enrolled in a randomized intervention trial: A qualitative study
Authors: Getz Vilde , Munkhaugen John , Lie Hanne C. , Dammen Toril 
Published: March 2023

ObjectivesSmoking is common in patients with cardiovascular disease. Despite strong recommendations for cessation and the existence of efficacious pharmacological and behavioral interventions, cessation rates remain low. Therefore, in this study, we explore perceived facilitators and barriers to smoking cessation in patients with atherosclerotic cardiovascular disease who have participated in a cessation intervention study.MethodsParticipants (N = 10) from the intervention arm of a randomized controlled study with access to free cessation support and pharmacological aids completed a semi-structured, in-depth telephone interview after a 6-monthfollow-up between October 2021 and July 2022. The interviews were audio recorded, transcribed, and analyzed according to principles of thematic analysis.ResultsThe mean age was 65.7 (range: 55–79) years, and three of the 10 participants were women. Among the participants, five had quit smoking, three had relapsed, and two were persistent smokers. The themes identified encompassed barriers and facilitators to cessation, both including individual and contextual factors. Barriers included the upsides of smoking, difficult life situations, addiction to smoking, smoking in social circles, perceived lack of support and understanding from health professionals. Facilitators included intrinsic motivation, concerns about the health condition, financial implications, specific behavioral strategies, positive influence from the social environment, and helpful components of the cessation intervention.ConclusionSmokers with cardiovascular disease who have attended a cessation intervention study report several facilitators weighted against barriers, interacting with the intention to cease smoking. The most important potentially modifiable factors of significance for cessation identified may be addressed through motivational interviews and focus groups with other smokers.
From digital museuming to on-site visiting: The mediation of cultural identity and perceived value
Authors: Deng Yuanbing , Zhang Xinhui , Zhang Bowen , Zhang Bei , Qin Jing 
Published: March 2023

IntroductionMuseums use digital resources to provide online services to the public, and a “digital museuming” boom has started. The mechanism of online museum visiting and its impact on willingness to visit on site has become an important issue of widespread concern. Therefore, based on the theory of presence and cognitive-emotional-behavioral theory, this paper introduces perceived value and cultural identity as mediating variables to explore the influence of the digital museuming experience on the willingness to visit on site from the audience’s perspective.MethodQuestionnaires were distributed, using the snowball sampling method, and 429 valid questionnaires were returned.ResultsThe empirical test presents the following results: (1) virtual reality technology multi-dimensionally expands the digital museuming experience; (2) immersion, interaction and available experience promote willingness to visit on-site; (3) hedonic experience in the process of digital museuming cannot be ignored; and (4) perceived value and cultural identity play a mediating role.DiscussionUser experience of visiting virtual museums, perceived value and cultural identity influence user willingness to visit museums in the field, but perceived value does not enhance the user’s cultural identity, maybe due to the inability of the online experience to increase the depth of the experience.
Shared and differential fractional amplitude of low-frequency fluctuation patterns at rest in major depressive disorders with or without sleep disturbance
Authors: Zheng Nanxi , Ou Yangpan , Li Huabing , Liu Feng , Xie Guojun , Li Ping , Lang Bing , Guo Wenbin 
Published: March 2023

ObjectiveSleep disturbances (SD) are commonly found in patients with major depressive disorder (MDD). This study aims to explore the influence of SD symptoms on clinical characteristics in patients with MDD and to investigate the shared and distinct fractional amplitude of low-frequency fluctuation (fALFF) patterns in these patients with or without SD symptoms.MethodsTwenty-four MDD patients with SD symptoms (Pa_s), 33 MDD patients without SD symptoms (Pa_ns) and 32 healthy controls (HCs) were included in this study. The fALFF and correlation analyses were applied to analyze the features of imaging and clinical data.ResultsPa_s showed more severe anxiety and depression than Pa_ns. Compared with Pa_ns, Pa_s exhibited increased fALFF value in the left precuneus. Patients shared abnormal fALFF in the frontal-occipital brain regions. There was a positive correlation between fALFF values of the left precuneus and sleep disturbance scores (r = 0.607, p = 0.0000056734) in all patients in addition to a negative correlation between fALFF values of the left MOG/cuneus and HAMD-17 total scores (r = −0.595, p = 0.002141) in Pa_s. The receiver operating characteristic (ROC) results of the fALFF could be used to discriminate Pa_s from Pa_ns with a specificity of 72.73% and a sensitivity of 70.83%.ConclusionPa_s displayed more serious anxiety and depression symptoms. Patients shared abnormal fALFF in the frontal-occipital brain regions, which may be a common characteristic for MDD. And increased fALFF value in the left precuneus might be a specific neuroimaging feature of MDD patients with SD symptoms.
Adverse childhood experiences affect the health of middle-aged and older people in China: The multiple mediating roles of sleep duration and life satisfaction
Authors: Yin Haojie , Qiu Xueying , Zhu Yan , Yang Qing 
Published: March 2023

BackgroundAlthough a significant amount of literature has examined the association between childhood adversity and adverse health outcomes, which may be affected by sleep duration and life satisfaction. However, this relationship has not been researched in the Chinese population. This study aimed to assess the association between childhood adversity and health outcomes, with sleep duration and life satisfaction as mediators.MethodsA total of 14,693 subjects aged 45 and over from the 2018 China Health and Retirement Longitudinal Study (CHARLS) were included. Taking childhood adversity as the independent variable, the health level of middle-aged and older individuals as the dependent variable, and sleep time and satisfaction as the mediating factors, Mplus 8.0 software was used to establish a structural equation model (SEM) to analyze the link between childhood adversity and health level and to explore the mediating effect of target mediators between childhood adversity and health level.ResultsIn this study, childhood adversity was positively associated with depression symptoms, activities of daily living (ADL), and the number of chronic diseases (r = 0.116, 0.026 and 0.050, respectively, P &lt; 0.001). Associations between adverse childhood experiences (ACEs) and depressive symptoms, ADL, and number of chronic diseases were mediated by sleep duration and life satisfaction, respectively.ConclusionAdversity experienced in childhood can affect the health status of middle-aged and older people. By ensuring adequate sleep and improving life satisfaction, health outcomes can be improved, and the negative effects of childhood adversity can be reduced.