bluuebunny/crossref_metadata_2025_split huggingface dataset:
External quality assurance program for diagnostic complement laboratories: evaluation of the results of the past seven years
Authors: Kirschfink Michael , Frazer-Abel Ashley , Balogh Emese , Goseberg Sabine , Weiss Nathalie , Prohászka Zoltán 
Published: March 2024

IntroductionThe complement external quality assurance (EQA) program was first organized in 2010 by a group of researchers working in diagnostic complement laboratories. Starting in 2016, INSTAND e.V., a German, non-profit interdisciplinary scientific medical society dedicated to providing expert EQA programs for medical laboratories, started organizing the EQAs for complement diagnostic laboratories together with the same group of experienced scientists and doctors who also work as EQA experts. The aim of the current work is to provide descriptive analysis of the past seven years’ complement EQA results and evaluate timeline changes in proficiency testing.MethodsEach year, in March and October, blinded samples (normal, pathological) were sent to the participating diagnostic laboratories, where complement parameters were evaluated exactly as in daily routine samples. Since no reference method/target values exist for these parameters, and participants used different units for measurement, the reported results were compared to the stable mean (Algorithm A) of the participants using the same method/measurement units. A reported result was qualified as “passed” if it fell into the 30-50% evaluation/target range around the mean of reported results (depending on the given parameter).ResultsWhile the number of participating laboratories has increased in the past years (from around 120 to 347), the number of complement laboratories providing multiple determinations remained mostly unchanged (around 30 worldwide). C3, C4, C1-inhibitor antigen and activity determinations provided the best proficiency results, with &gt;90% passing quotas in the past years, independent of the applied method. Determination of the functional activity of the three activation pathways was good in general, but results showed large variance, especially with the pathological samples. Complement factor C1q and regulators FH and FI are determined by only a few laboratories, with variable outcomes (in general in the 85-90% pass range). Activation products sC5b-9 and Bb were determined in 30 and 10 laboratories, respectively, with typical passing quotas in the 70-90% range, without a clear tendency over the past years.ConclusionWith these accumulated data from the past seven years, it is now possible to assess sample-, method-, and evaluation related aspects to further improve proficiency testing and protocolize diagnostic complement determinations.
A novel major facilitator superfamily-type tripartite efflux system CprABC mediates resistance to polymyxins in Chryseobacterium sp. PL22-22A
Authors: Zhang Lu , Wang Miao , Qi Rui , Yang Yilin , Liu Ya , Ren Nianqing , Feng Zihan , Liu Qihao , Cao Guangxiang , Zong Gongli 
Published: March 2024

BackgroundPolymyxin B (PMB) and polymyxin E (colistin, CST) are polymyxin antibiotics, which are considered last-line therapeutic options against multidrug-resistant Gram-negative bacteria in serious infections. However, there is increasing risk of resistance to antimicrobial drugs. Effective efflux pump inhibitors (EPIs) should be developed to help combat efflux pump-mediated antibiotic resistance.MethodsChryseobacterium sp. PL22-22A was isolated from aquaculture sewage under selection with 8 mg/L PMB, and then its genome was sequenced using Oxford Nanopore and BGISEQ-500 platforms. Cpr (Chryseobacterium Polymyxins Resistance) genes encoding a major facilitator superfamily-type tripartite efflux system, were found in the genome. These genes, and the gene encoding a truncation mutant of CprB from which sequence called CprBc was deleted, were amplified and expressed/co-expressed in Escherichia coli DH5α. Minimum inhibitory concentrations (MICs) of polymyxins toward the various E. coli heterologous expression strains were tested in the presence of 2–128 mg/L PMB or CST. The pumping activity of CprABC was assessed via structural modeling using Discovery Studio 2.0 software. Moreover, the influence on MICs of baicalin, a novel MFS EPI, was determined, and the effect was analyzed based on homology modeling.ResultsMultidrug-resistant bacterial strain Chryseobacterium sp. PL22-22A was isolated in this work; it has notable resistance to polymyxin, with MICs for PMB and CST of 96 and 128 mg/L, respectively. A novel MFS-type tripartite efflux system, named CprABC, was identified in the genome of Chryseobacterium sp. PL22-22A. Heterologous expression and EPI assays indicated that the CprABC system is responsible for the polymyxin resistance of Chryseobacterium sp. PL22-22A. Structural modeling suggested that this efflux system provides a continuous conduit that runs from the CprB funnel through the CprC porin domain to pump polymyxins out of the cell. A specific C-terminal α-helix, CprBc, has an activation function on polymyxin excretion by CprB. The flavonoid compound baicalin was found to affect the allostery of CprB and/or obstruct the substrate conduit, and thus to inhibit extracellular polymyxin transport by CprABC.ConclusionNovel MFS-type tripartite efflux system CprABC in Chryseobacterium sp. PL22-22A mediates resistance to polymyxins, and baicalin is a promising EPI.
Intestinal melatonin levels and gut microbiota homeostasis are independent of the pineal gland in pigs
Authors: Zheng Jiaming , Zhou Yewen , Zhang Di , Ma Kezhe , Gong Yuneng , Luo Xuan , Liu Jiali , Cui Sheng 
Published: March 2024

IntroductionMelatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model to investigate the functions of pineal MEL and its relationship with various diseases. However, the effect of PINX on the gastrointestinal tract (GIT) MEL levels and gut microbiome in pigs has not been previously reported.MethodsBy using a newly established pig PINX model, we detected the levels of MEL in the GIT by liquid chromatography–tandem mass spectrometry. In addition, we examined the effects of PINX on the expression of MEL synthesis enzymes, intestinal histomorphology, and the intestinal barrier. Furthermore, 16S rRNA sequencing was performed to analyze the colonic microbiome.ResultsPINX reduced serum MEL levels but did not affect GIT MEL levels. Conversely, MEL supplementation increased MEL levels in the GIT and intestinal contents. Neither PINX nor MEL supplementation had any effect on weight gain, organ coefficient, serum biochemical indexes, or MEL synthetase arylalkylamine N-acetyltransferase (AANAT) expression in the duodenum, ileum, and colon. Furthermore, no significant differences were observed in the intestinal morphology or intestinal mucosal barrier function due to the treatments. Additionally, 16S rRNA sequencing revealed that PINX had no significant impact on the composition of the intestinal microbiota. Nevertheless, MEL supplementation decreased the abundance of Fibrobacterota and increased the abundance of Actinobacteriota, Desulfobacterota, and Chloroflexi.ConclusionWe demonstrated that synthesis of MEL in the GIT is independent of the pineal gland. PINX had no influence on intestinal MEL level and microbiota composition in pigs, while exogenous MEL alters the structure of the gut microbiota.
Metagenomics reveals the response of desert steppe microbial communities and carbon-nitrogen cycling functional genes to nitrogen deposition
Authors: Ye He , Zhao Yu , He Shilong , Wu Zhendan , Yue Mei , Hong Mei 
Published: March 2024

IntroductionNitrogen (N) deposition seriously affects the function of carbon (C) and N cycling in terrestrial ecosystems by altering soil microbial communities, especially in desert steppe ecosystems. However, there is a need for a comprehensive understanding of how microorganisms involved in each C and N cycle process respond to N deposition.MethodsIn this study, shotgun metagenome sequencing was used to investigate variations in soil C and N cycling-related genes in the desert steppe in northern China after 6 years of the following N deposition: N0 (control); N30 (N addition 30 kg ha−1 year−1): N50 (N addition 50 kg ha−1 year−1).ResultsN deposition significantly increased the relative abundance of Actinobacteria (P &lt; 0.05) while significantly decreased the relative abundances of Proteobacteria and Acidobacteria (P &lt; 0.05). This significantly impacted the microbial community composition in desert steppe soils. The annual addition or deposition of 50 kg ha−1 year−1 for up to 6 years did not affect the C cycle gene abundance but changed the C cycle-related microorganism community structure. The process of the N cycle in the desert steppe was affected by N deposition (50 kg ha−1 year−1), which increased the abundance of the pmoA-amoA gene related to nitrification and the nirB gene associated with assimilation nitrite reductase. There may be a niche overlap between microorganisms involved in the same C and N cycling processes.DiscussionThis study provides new insights into the effects of N deposition on soil microbial communities and functions in desert steppe and a better understanding of the ecological consequences of anthropogenic N addition.
Time of the day and season distribution among stroke code subtypes: differences between ischemic stroke, intracranial hemorrhage, and stroke mimic
Authors: Menéndez Albarracín Alex , Valls Carbó Adrián , Rabaneda Lombarte Neus , Yugueros Baena Bárbara , Carbonell Gisbert Jaime , Flores-Pina Belén , Larrañaga De Bofarull Maria-Clara , Martínez Sánchez Marina , Hernández-Pérez María , Bustamante Rangel Alejandro , Dorado Bouix Laura , Gomis Cortina Meritxell , Millán Tornè Mònica , Pérez de la Ossa Natalia 
Published: March 2024

BackgroundCircadian variations in the timing of the onset of stroke symptoms have been described, showing a morning excess of cardiovascular risk. To date, no differences have been found between stroke subtype and time distribution throughout the day. The present study aims to compare the seasonal and circadian rhythm of symptoms onset in ischemic, hemorrhagic, and stroke mimic patients.MethodsThis study was conducted prospectively at a hospital and involved a cohort of stroke alert patients from 2018 to 2021. Stroke subtypes were classified as ischemic stroke, intracerebral hemorrhage (ICH), transient ischemic attack (TIA), and stroke mimic. Clinical variables were recorded, and each patient was assigned to a 4-h interval of the day according to the time of onset of symptoms; unwitnessed stroke patients were analyzed separately. Seasonal changes in stroke distribution were analyzed at 3-month intervals.ResultsA total of 2,348 patients were included in this analysis (ischemic 67%, ICH 13%, mimic 16%, and TIA 3%). Regardless of stroke subtype, most of the patients were distributed between 08–12 h and 12–16 h. Significant differences were found in the time distribution depending on stroke subtype, with ICH predominating in the 4–8 h period (dawn), most of which were hypertensive, TIA in the 12–16 h period (afternoon), and stroke mimic in the 20 h period (evening). The ischemic stroke was evenly distributed throughout the different periods of the day. There were no differences in the seasonal pattern between different stroke subtypes, with winter being the one that accumulated the most cases.ConclusionThe present study showed different circadian patterns of stroke subtypes, with a predominance of ICH at dawn and stroke mimic in the afternoon. The stroke circadian rhythm resembles previous studies, with a higher incidence in the morning and a second peak in the afternoon.
Toluene alters the intrinsic excitability and excitatory synaptic transmission of basolateral amygdala neurons
Authors: Braunscheidel Kevin , Okas Michael , Woodward John J. 
Published: March 2024

IntroductionInhalant abuse is an important health issue especially among children and adolescents who often encounter these agents in the home. Research into the neurobiological targets of inhalants has lagged behind that of other drugs such as alcohol and psychostimulants. However, studies from our lab and others have begun to reveal how inhalants such as the organic solvent toluene affect neurons in key addiction related areas of the brain including the ventral tegmental area, nucleus accumbens and medial prefrontal cortex. In the present study, we extend these findings and examine the effect of toluene on electrophysiological responses of pyramidal neurons in the basolateral amygdala BLA, a region important for generating emotional and reward based information needed to guide future behavior.MethodsWhole-cell patch-clamp electrophysiology recordings of BLA pyramidal neurons in rat brain slices were used to assess toluene effects on intrinsic excitability and excitatory glutamatergic synaptic transmission.ResultsAcute application of 3 mM but not 0.3 mM toluene produced a small but significant (~20%) increase in current-evoked action potential (AP) firing that reversed following washout of the toluene containing solution. The change in firing during exposure to 3 mM toluene was accompanied by selective changes in AP parameters including reduced latency to first spike, increased AP rise time and decay and a reduction in the fast after-hyperpolization. To examine whether toluene also affects excitatory synaptic signaling, we expressed channelrhodopsin-2 in medial prefrontal cortex neurons and elicited synaptic currents in BLA neurons via light pulses. Toluene (3 mM) reduced light-evoked AMPA-mediated synaptic currents while a lower concentration (0.3 mM) had no effect. The toluene-induced reduction in AMPA-mediated BLA synaptic currents was prevented by the cannabinoid receptor-1 antagonist AM281.DiscussionThese findings are the first to demonstrate effects of acute toluene on BLA pyramidal neurons and add to existing findings showing that abused inhalants such as toluene have significant effects on neurons in brain regions involved in natural and drug induced reward.
NutriGreen image dataset: a collection of annotated nutrition, organic, and vegan food products
Authors: Drole Jan , Pravst Igor , Eftimov Tome , Koroušić Seljak Barbara 
Published: March 2024

IntroductionIn this research, we introduce the NutriGreen dataset, which is a collection of images representing branded food products aimed for training segmentation models for detecting various labels on food packaging. Each image in the dataset comes with three distinct labels: one indicating its nutritional quality using the Nutri-Score, another denoting whether it is vegan or vegetarian origin with the V-label, and a third displaying the EU organic certification (BIO) logo.MethodsTo create the dataset, we have used semi-automatic annotation pipeline that combines domain expert annotation and automatic annotation using a deep learning model.ResultsThe dataset comprises a total of 10,472 images. Among these, the Nutri-Score label is distributed across five sub-labels: Nutri-Score grade A with 1,250 images, grade B with 1,107 images, grade C with 867 images, grade D with 1,001 images, and grade E with 967 images. Additionally, there are 870 images featuring the V-Label, 2,328 images showcasing the BIO label, and 3,201 images without before-mentioned labels. Furthermore, we have fine-tuned the YOLOv5 segmentation model to demonstrate the practicality of using these annotated datasets, achieving an impressive accuracy of 94.0%.DiscussionThese promising results indicate that this dataset has significant potential for training innovative systems capable of detecting food labels. Moreover, it can serve as a valuable benchmark dataset for emerging computer vision systems.
Von-Hipple Lindau syndrome with family history: a case report and seventeen years follow-up study
Authors: Fan XueMei , Wang Shuai , Chen Tianwen , Hu Wei , Yang Hui 
Published: March 2024

BackgroundVon-Hipple Lindau syndrome is an uncommon autosomal dominant disorder. 17 years ago we diagnosed a young woman with VHL syndrome validated by Sanger sequencing, her family members were genetically tested as well, and 187 healthy people were randomly selected for VHL genetic testing as controls. We analyze the clinical and genetic characteristics of VHL syndrome in a Chinese lineage and with 17-year follow-up.Case presentationA woman was finally diagnosed with VHL syndrome due to the detection of a missense mutation c.353T &gt; C in exon 2 of the short arm of chromosome 3, which resulted in a leucine substitution at amino acid 118 of the encoded protein by a proline, which may be thought the main cause of the disease. The same mutation was observed in two other family members, their clinical symptoms are not entirely identical. However, this mutation was not found in other family members or 187 healthy controls. She clinically presented with central nervous system hemangioblastomas, clear renal cell carcinoma, and pancreatic neuroendocrine neoplasms, despite the multi-organ involvement and several relapses during the disease, the patients survive well for she was treated with aggressive surgery early in the course of the plaguing symptoms, whereas patients who are not aggressively treated have a poorer prognosis.ConclusionThe clinical presentation of VHL syndrome is atypical, and early identification and treatment of VHL syndrome is possible by genetic testing techniques. Multiple relapses occurred during the course of the disease, but early diagnosis and aggressive treatment allowed the patients to survive well.
Case report: Therapy-related myeloid neoplasms in three pediatric cases with medulloblastoma
Authors: Mak Li Shun , Li Xiuling , Chan Wilson Y. K. , Leung Alex W. K. , Cheuk Daniel K. L. , Yuen Liz Y. P. , So Jason C. C. , Ha Shau Yin , Liu Anthony P. Y. 
Published: March 2024

IntroductionMedulloblastoma is the most common malignant brain tumor in children, often requiring intensive multimodal therapy, including chemotherapy with alkylating agents. However, therapy-related complications, such as therapy-related myeloid neoplasms (t-MNs), can arise, particularly in patients with genetic predisposition syndromes. This case report presents three pediatric cases of medulloblastoma with subsequent development of t-MNs, highlighting the potential role of genetic predisposition and the importance of surveillance for hematological abnormalities in long-term survivors.Case presentationWe describe three cases of pediatric medulloblastoma who developed t-MNs after receiving chemotherapy, including alkylating agents. Two of the patients had underlying genetic predisposition syndromes (TP53 pathologic variants). The latency period between initial diagnosis of medulloblastoma and the development of secondary cancer varied among the cases, ranging from 17 to 65 months. The three cases eventually succumbed from secondary malignancy, therapy-related complications and progression of primary disease, respectively.ConclusionsThis report highlights the potential association between genetic predisposition syndromes and the development of therapy-related myeloid neoplasms in pediatric medulloblastoma survivors. It underscores the importance of surveillance for hematological abnormalities among such patients.
Lysyl oxidase-like 4 promotes the invasiveness of triple-negative breast cancer cells by orchestrating the invasive machinery formed by annexin A2 and S100A11 on the cell surface
Authors: Takahashi Tetta , Tomonobu Nahoko , Kinoshita Rie , Yamamoto Ken-ichi , Murata Hitoshi , Komalasari Ni Luh Gede Yoni , Chen Youyi , Jiang Fan , Gohara Yuma , Ochi Toshiki , Ruma I Made Winarsa , Sumardika I Wayan , Zhou Jin , Honjo Tomoko , Sakaguchi Yoshihiko , Yamauchi Akira , Kuribayashi Futoshi , Kondo Eisaku , Inoue Yusuke , Futami Junichiro , Toyooka Shinichi , Zamami Yoshito , Sakaguchi Masakiyo 
Published: March 2024

BackgroundOur earlier research revealed that the secreted lysyl oxidase-like 4 (LOXL4) that is highly elevated in triple-negative breast cancer (TNBC) acts as a catalyst to lock annexin A2 on the cell membrane surface, which accelerates invasive outgrowth of the cancer through the binding of integrin-β1 on the cell surface. However, whether this machinery is subject to the LOXL4-mediated intrusive regulation remains uncertain.MethodsCell invasion was assessed using a transwell-based assay, protein–protein interactions by an immunoprecipitation–Western blotting technique and immunocytochemistry, and plasmin activity in the cell membrane by gelatin zymography.ResultsWe revealed that cell surface annexin A2 acts as a receptor of plasminogen via interaction with S100A10, a key cell surface annexin A2-binding factor, and S100A11. We found that the cell surface annexin A2/S100A11 complex leads to mature active plasmin from bound plasminogen, which actively stimulates gelatin digestion, followed by increased invasion.ConclusionWe have refined our understanding of the role of LOXL4 in TNBC cell invasion: namely, LOXL4 mediates the upregulation of annexin A2 at the cell surface, the upregulated annexin 2 binds S100A11 and S100A10, and the resulting annexin A2/S100A11 complex acts as a receptor of plasminogen, readily converting it into active-form plasmin and thereby enhancing invasion.
Cost-effectiveness of immune checkpoint inhibitors in treating metastatic urothelial cancer
Authors: Yang Li-Yu , Li Jian-Ri , Chen Chuan-Shu , Cheng Chen-Li , Hung Sheng-Chun , Chiu Kun-Yuan , Yang Cheng-Kuang , Hsu Chiann-Yi , Wang Shian-Shiang 
Published: March 2024

Objectives: Immune checkpoint inhibitor (ICI) is an important treatment option for metastatic urothelial carcinoma (mUC) patients. A lot of clinical evidence proved the survival benefits of ICI, but cost-effectiveness of the treatment remains unclear. This study evaluates the cost-effectiveness of the ICIs treatment in different sequences among mUC patients.Methods: We retrospectively analyzed mUC patients who had been treated at our hospital between January 2016 and December 2020. These patients received chemotherapy with or without ICI treatment (Pembrolizumab, Atezolizumab, Nivolumab, Durvalumab, or Avelumab). The patients were divided into three different groups: receiving chemotherapy alone, receiving a combination of first-line ICI and chemotherapy (ICI combination therapy), and receiving chemotherapy as the first-line treatment followed by second-line ICI therapy (Subsequent ICI therapy). The primary endpoint was cost per life day, while lifetime medical costs and overall survival were also evaluated.Results: The 74 enrolled patients had a median age of 67.0 years, with 62.2% being male. Of these patients, 23 had received chemotherapy only, while the remaining patients had received combined therapy with ICI in either first-line or as subsequent agents (37 patients had ever received atezolizumab, 18 pembrolizumab, 1 Durvalumab, 1 Nivolumab, and 1 Avelumab separately.). Fifty-five patients (74.3%, 55/74) received cisplatin amongst all the patients who underwent chemotherapy. Median overall survival was 27.5 months (95% CI, 5.2–49.9) in the first-line ICI combination therapy group, and 8.9 months (95% CI, 7.1–10.8) in the chemotherapy only. Median overall survival for the subsequent ICI therapy group was not reached. The median lifetime cost after metastatic UC diagnosis was USD 31,221. The subsequent ICI therapy group had significantly higher costs when compared with the ICI combination therapy group (155.8 USD per day, [IQR 99.0 to 220.5] v 97.8 USD per day, [IQR 60.8 to 159.19], p = 0.026). Higher insurance reimbursement expenses for the subsequent ICI therapy group were observed when compared with the ICI combination therapy group.Conclusion: Our real-world data suggests that first line use of ICI combined with chemotherapy demonstrates better cost-effectiveness and similar survival outcomes for mUC patients, when compared with subsequent ICI therapy after chemotherapy.