bluuebunny/crossref_metadata_2025 huggingface dataset:
Patterns of the relationship between the Secchi disk depth and the optical characteristics of water in the Neva Estuary (Baltic Sea): the influence of environmental variables
Authors: Golubkov Mikhail , Golubkov Sergey
Published: March 2024

The Secchi disc depth (Dsd) measurement is widely used to monitor eutrophication and the quality of the aquatic environment. This study aimed to investigate the relationship between Dsd and various factors, including the coefficient of attenuation of photosynthetically active radiation [Kd (PAR)], the depth of the euphotic zone (Deu), PAR at the Secchi disk depth (Esd) and the absorption coefficient of PAR (F) in the Neva Estuary, one of largest estuaries of the Baltic Sea. Environmental variables impacting these indices were identified using data collected from midsummer 2012 to 2020. The Dsd values in the estuary ranged from 0.3 to 4.0 m, with an average value of 1.8 m, while the Deu/Dsd ratio ranged from 1.5 to 6.0 with an average value of 2.8. These values were significantly lower than those observed in the open waters of the Baltic Sea. The highest Deu/Dsd ratio was observed in turbid waters characterized by high Kd(PAR) and low Dsd. Contrary to expectations, Dsd did not exhibit a significant relationship with the concentration of chlorophyll a, raising doubts about the utility of historical Dsd data for reconstructing phytoplankton development in the estuary. Principal component analysis did not identify the primary environmental variables strongly affecting the optical characteristics of water. However, recursive partitioning of the dataset using analysis of variance (CART approach) revealed that the concentration of suspended mineral matter (SMM) was the primary predictor of Deu/Dsd, Kd(PAR), and F. This SMM was associated with the frequent resuspension of bottom sediments during windy weather and construction activities in the estuary. Concentrations of suspended organic matter and the depth of the water area were found to be less significant as environmental variables. Furthermore, the CART approach demonstrated that different combinations of environmental variables in estuarine waters could result in similar optical indicator values. To reliably interpret the data and determine the optical characteristics of water in estuaries from Dsd, more complex models incorporating machine learning and neural connections are required. Additionally, reference determinations of Esd in various regions with specific sets of environmental variables would be valuable for comparative analyses and better understanding of estuarine systems.
Quantitative analysis and comprehensive evaluation of coarse aggregate morphology for asphalt pavement
Authors: Zhang Chen , Cheng Shiqiang , Kong Qingxin , Jiang Yong
Published: March 2024

The morphological characteristics of coarse aggregate play a crucial role in the mechanical properties, durability, and construction performance of asphalt mixtures and pavements in highway engineering. This study aims to quantitatively analyze the morphological characteristics of coarse aggregate and establish comprehensive evaluation indicators for its quality and performance. Two-dimensional cross-sectional images of coarse aggregates are obtained using the self-developed laser scanning equipment, and edge features are extracted using the Canny operator and edge tracing algorithm. Six morphological characteristic indicators are selected, and factor analysis is employed to propose comprehensive shape and edge feature for coarse aggregates. The results show that the proposed evaluation indicators effectively capture the shape and edge feature of coarse aggregates, with the exception of roughness, which is deemed unsuitable for evaluation. Factor analysis of six indicator values in 2,700 two-dimensional images led to the proposal of Shape Factor (SF) and Edge Feature Factor (EFF) as significant factors affecting aggregate shape and edge characteristics, respectively. Following optimization, SF ranged from 0.041 to 1.793, while EFF ranged from 0.368 to 1.745. The spearman’s rank correlation coefficient revealed strong correlations between the evaluation of coarse aggregate shape and edge features using the line laser-based comprehensive evaluation index. Specifically, correlation coefficients of 0.864 and 0.805 exceeded those of commonly used methods such as AIMS and X-ray CT, indicating the rationality and accuracy of the self-developed laser scanning device in evaluating aggregate morphology. This research provides strong support for the construction of highway engineering and optimization of coarse aggregate production and supply.
Critical bloodstream infection caused by Chromobacterium violaceum: a case report in a 15-year-old male with sepsis-induced cardiogenic shock and purpura fulminans
Authors: Wang Xueqing , Tu Yunliang , Chen Yingqun , Yang Huilin , Luo Minghua , Li Yanyan , Huang Lei , Luo Hua
Published: March 2024

Chromobacterium violaceum (C. violaceum) is a gram-negative bacillus that is widespread in tropical and subtropical areas. Although C. violaceum rarely infects humans, it can cause critical illness with a mortality rate above 50%. Here, we report the successful treatment of a 15-year-old male who presented with bloodstream infection of C. violaceum along with sepsis, specific skin lesions, and liver abscesses. Cardiogenic shock induced by sepsis was reversed by venoarterial extracorporeal membrane oxygenation (VA ECMO). Moreover, C. violaceum-related purpura fulminans, which is reported herein for the first time, was ameliorated after treatment. This case report demonstrates the virulence of C. violaceum with the aim of raising clinical awareness of this disease.
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

Background

Polymyxin 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.

Methods

Chryseobacterium 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.

Results

Multidrug-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.

Conclusion

Novel 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

Introduction

Melatonin (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.

Methods

By 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.

Results

PINX 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.

Conclusion

We 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

Introduction

Nitrogen (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.

Methods

In 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).

Results

N deposition significantly increased the relative abundance of Actinobacteria (P < 0.05) while significantly decreased the relative abundances of Proteobacteria and Acidobacteria (P < 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.

Discussion

This 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.
Identification of a novel xanthan-binding module of a multi-modular Cohnella sp. xanthanase
Authors: Han Rui , Baudrexl Melanie , Ludwig Christina , Berezina Oksana V. , Rykov Sergey V. , Liebl Wolfgang
Published: March 2024

A new strain of xanthan-degrading bacteria identified as Cohnella sp. has been isolated from a xanthan thickener for food production. The strain was able to utilize xanthan as the only carbon source and to reduce the viscosity of xanthan-containing medium during cultivation. Comparative analysis of the secretomes of Cohnella sp. after growth on different media led to the identification of a xanthanase designated as CspXan9, which was isolated after recombinant production in Escherichia coli. CspXan9 could efficiently degrade the β-1,4-glucan backbone of xanthan after previous removal of pyruvylated mannose residues from the ends of the native xanthan side chains by xanthan lyase treatment (XLT-xanthan). Compared with xanthanase from Paenibacillus nanensis, xanthanase CspXan9 had a different module composition at the N- and C-terminal ends. The main putative oligosaccharides released from XLT-xanthan by CspXan9 cleavage were tetrasaccharides and octasaccharides. To explore the functions of the N- and C-terminal regions of the enzyme, truncated variants lacking some of the non-catalytic modules (CspXan9-C, CspXan9-N, CspXan9-C-N) were produced. Enzyme assays with the purified deletion derivatives, which all contained the catalytic glycoside hydrolase family 9 (GH9) module, demonstrated substantially reduced specific activity on XLT-xanthan of CspXan9-C-N compared with full-length CspXan9. The C-terminal module of CspXan9 was found to represent a novel carbohydrate-binding module of family CBM66 with binding affinity for XLT-xanthan, as was shown by native affinity polyacrylamide gel electrophoresis in the presence of various polysaccharides. The only previously known binding function of a CBM66 member is exo-type binding to the non-reducing fructose ends of the β-fructan polysaccharides inulin and levan.
Effects of electroacupuncture on postoperative cognitive dysfunction and its underlying mechanisms: a literature review of rodent studies
Authors: Zhao Wenbo , Zou Wei
Published: March 2024

With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials.
Case report: Insulinoma masquerades as epilepsy – quantitative EEG analysis
Authors: Kostolanska Natalia , Klimes Petr , Kocvarova Jitka , Pikulova Hana , Strycek Ondrej , Brazdil Milan , Dolezalova Irena
Published: March 2024

Insulinomas are rare gastrointestinal tumors with an incidence of 1–3 per million inhabitants annually. These tumors result in excessive insulin production, culminating in hypoglycemia. Such hypoglycemia triggers various central nervous system (CNS) manifestations, including headache, confusion, abnormal behavior, and epileptic seizures, which can lead to misdiagnosis as epilepsy. This case report documents a 46-year-old male who presented seizure-like episodes. Episodes occurred mainly during the night, lasting several minutes to hours. Initial seizures were characterized by bizarre behavior and altered responsiveness. Over time, seizure frequency, complexity, and severity escalated. We managed to record two episodes during long-term EEG and report, as the first ones, the detailed quantitative EEG analysis of these hypoglycemia-related events. EEG changes preceded the development of clear-cut pathological motor activity in tens of minutes and were present in all investigated frequency bands. The development of profound motor activity was associated with other increases in EEG power spectra in all frequencies except for delta. The most pronounced changes were found over the left temporal region, which can be the most susceptible to hypoglycemia. In our patient, the seizure-like episodes completely disappeared after the insulinoma removal, which demonstrates their relationship to hypoglycemia.
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

Background

Circadian 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.

Methods

This 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.

Results

A 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.

Conclusion

The 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

Introduction

Inhalant 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.

Methods

Whole-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.

Results

Acute 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.

Discussion

These 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

Introduction

In 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.

Methods

To create the dataset, we have used semi-automatic annotation pipeline that combines domain expert annotation and automatic annotation using a deep learning model.

Results

The 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%.

Discussion

These 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

Background

Von-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 presentation

A woman was finally diagnosed with VHL syndrome due to the detection of a missense mutation c.353T > 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.

Conclusion

The 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

Introduction

Medulloblastoma 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 presentation

We 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.

Conclusions

This 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

Background

Our 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.

Methods

Cell 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.

Results

We 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.

Conclusion

We 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.
Effect of network architecture on physics-informed deep learning of the Reynolds-averaged turbulent flow field around cylinders without training data
Authors: Harmening Jan Hauke , Peitzmann Franz-Josef , el Moctar Ould
Published: March 2024

Unsupervised physics-informed deep learning can be used to solve computational physics problems by training neural networks to satisfy the underlying equations and boundary conditions without labeled data. Parameters such as network architecture and training method determine the training success. However, the best choice is unknown a priori as it is case specific. Here, we investigated network shapes, sizes, and types for unsupervised physics-informed deep learning of the two-dimensional Reynolds-averaged flow around cylinders. We trained mixed-variable networks and compared them to traditional models. Several network architectures with different shape factors and sizes were evaluated. The models were trained to solve the Reynolds-averaged Navier-Stokes equations incorporating Prandtl’s mixing length turbulence model. No training data were deployed to train the models. The superiority of the mixed-variable approach was confirmed for the investigated high Reynolds number flow. The mixed-variable models were sensitive to the network shape. For the two cylinders, differently deep networks showed superior performance. The best fitting models were able to capture important flow phenomena such as stagnation regions, boundary layers, flow separation, and recirculation. We also encountered difficulties when predicting high Reynolds number flows without training data.
Expression of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in the rat submandibular gland is influenced by pre- and post-natal high-fat diet exposure
Authors: Sangsuriyothai Pornchanok , Watari Ippei , Serirukchutarungsee Saranya , Satrawaha Sirichom , Podyma-Inoue Katarzyna Anna , Ono Takashi
Published: March 2024

Background: Incretins, i.e., glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) promote insulin secretion to reduce postprandial blood sugar. Previous studies found incretins in the salivary glands. However, the role of GLP-1 and GIP in the submandibular gland (SMG) is unclear. This study investigates the effects of a high-fat diet (HFD) on the expression of GLP-1 and GIP throughout the development of rat SMG.

Methods: Pregnant 11-week-old Wistar rats were divided into two groups: those fed on a standard diet (n = 5) and those fed on a HFD (n = 5). From day 7 of pregnancy and throughout the lactation period, all the rats were fed on either a chow diet or HFD. The newborns were divided into four subgroups (n = 6): standard diet males (SM), HFD males (HM), standard diet females (SF), and HFD females (HF). The SMGs of 3- and 10-week-old rats from each subgroup were collected under general anesthesia. Moreover, body weight, food intake, and fasting blood sugar were measured. The mRNA expression of GLP-1 and GIP was quantified, and the localization was observed using immunohistochemistry (p < 0.05).

Results: GLP-1 mRNA expression was statistically significantly more upregulated in HM than in HF at 3 weeks. Moreover, GLP-1 mRNA expression was significantly higher in HM than in both SM and HF at 10 weeks. Although a decreasing trend was observed in GIP mRNA expression in both 3- and 10-week-old rats fed on a HFD, a significant difference between HM and SM only occurred at 3 weeks. Furthermore, the GIP mRNA expression of HM was lower than that of HF at 10 weeks. Immunohistochemical staining revealed GLP-1 and GIP expression mainly in the SMG duct system. Moreover, vacuolated cytoplasm in the duct was observed in rats fed on a HFD.

Conclusion: Exposure to HFD during pre- and post-natal periods increased GLP-1 mRNA expression in the SMGs of male rats. However, GIP expression decreased following the HFD in male newborns. Furthermore, a decreasing trend of GIP mRNA expression was observed in male newborns after HFD feeding. Sex influenced incretin hormones secretion and obesity-related conditions. HFD during pre- and post-natal periods reprograms the epigenome, contributing to subsequent disease development.
Mapping QTL associated with resistance to Pseudomonas syringae pv. actinidiae in kiwifruit (Actinidia chinensis var. chinensis)
Authors: Flay Casey , Symonds V. Vaughan , Storey Roy , Davy Marcus , Datson Paul
Published: March 2024

Pseudomonas syringae pv. actinidiae (Psa) is a bacterial pathogen of kiwifruit. This pathogen causes leaf-spotting, cane dieback, wilting, cankers (lesions), and in severe cases, plant death. Families of diploid A. chinensis seedlings grown in the field show a range of susceptibilities to the disease with up to 100% of seedlings in some families succumbing to Psa. But the effect of selection for field resistance to Psa on the alleles that remain in surviving seedlings has not been assessed. The objective of this work was to analyse, the effect of plant removal from Psa on the allele frequency of an incomplete-factorial-cross population. This population was founded using a range of genotypically distinct diploid A. chinensis var. chinensis parents to make 28 F1 families. However, because of the diversity of these families, low numbers of surviving individuals, and a lack of samples from dead individuals, standard QTL mapping approaches were unlikely to yield good results. Instead, a modified bulk segregant analysis (BSA) overcame these drawbacks while reducing the costs of sampling and sample processing, and the complexity of data analysis. Because the method was modified, part one of this work was used to determine the signal strength required for a QTL to be detected with BSA. Once QTL detection accuracy was known, part two of this work analysed the 28 families from the incomplete-factorial-cross population that had multiple individuals removed due to Psa infection. Each family was assigned to one of eight bulks based on a single parent that contributed to the families. DNA was extracted in bulk by grinding sampled leaf discs together before DNA extraction. Each sample bulk was compared against a bulk made up of WGS data from the parents contributing to the sample bulk. The deviation in allele frequency from the expected allele frequency within surviving populations using the modified BSA method was able to identify 11 QTLs for Psa that were present in at least two analyses. The identification of these Psa resistance QTL will enable marker development to selectively breed for resistance to Psa in future kiwifruit breeding programs.
Genome wide characterization and expression analysis of CrRLK1L gene family in wheat unravels their roles in development and stress-specific responses
Authors: Gawande Nilesh D. , Sankaranarayanan Subramanian
Published: March 2024

Catharanthus roseus receptor-like kinase 1-like (CrRLK1L) genes encode a subfamily of receptor-like kinases (RLK) that regulate diverse processes during plant growth, development, and stress responses. The first CrRLK1L was identified from the Catharanthus roseus, commonly known as Madagascar periwinkle. Subsequently, CrRLK1L gene families have been characterized in many plants. The genome of T. aestivum encodes 15 CrRLK1L genes with 43 paralogous copies, with three homeologs each, except for -2-D and -7-A, which are absent. Chromosomal localization analysis revealed a markedly uneven distribution of CrRLK1L genes across seven different chromosomes, with chromosome 4 housing the highest number of genes, while chromosome 6 lacked any CrRLK1L genes. Tissue-specific gene expression analysis revealed distinct expression patterns among the gene family members, with certain members exhibiting increased expression in reproductive tissues. Gene expression analysis in response to various abiotic and biotic stress conditions unveiled differential regulation of gene family members. Cold stress induces CrRLK1Ls -4-B and -15-A while downregulating -3-A and -7B. Drought stress upregulates -9D, contrasting with the downregulation of -7D. CrRLK1L-15-B and -15-D were highly induced in response to 1 hr of heat, and combined drought and heat stress, whereas -10-B is downregulated. Similarly, in response to NaCl stress, only CrRLK1L1 homeologs were induced. Fusarium graminearum and Claviceps purpurea inoculation induces homeologs of CrRLK1L-6 and -7. The analysis of cis-acting elements in the promoter regions identified elements crucial for plant growth and developmental processes. This comprehensive genome-wide analysis and expression study provides valuable insights into the essential functions of CrRLK1L members in wheat.
Phylogeny of genera in Maleae (Rosaceae) based on chloroplast genome analysis
Authors: Sun Jiahui , Zhao Dan , Qiao Ping , Wang Yiheng , Wu Ping , Wang Keren , Guo Lanping , Huang Luqi , Zhou Shiliang
Published: March 2024

In Rosaceae, the replacement of the traditional four-subfamily division (Amygdaloideae or Prunoideae, Maloideae, Rosoideae, and Spiraeoideae) by the three-subfamily division (Dryadoideae, Rosoideae, and Amygdaloideae), the circumscription, systematic position, and phylogeny of genera in Maleae need to be reconsidered. The study aimed to circumscribe Maleae, pinpoint its systematic position, and evaluate the status of all generally accepted genera in the tribe using complete chloroplast genome data. Results indicated that Maleae consisted of pome-bearing genera that belonged to Maloideae as well as four genera (Gillenia, Kageneckia, Lindleya, and Vauquelinia) that were formerly considered to be outside Maloideae. The tribe could be subdivided into four subtribes: Gilleniinae (Gillenia), Lindleyinae (Kageneckia and Lindleya), Vaugueliniinae (Vauquelinia), and Malinae (all other genera; the core Maleae). Among the 36 recognized genera, Aria, Docyniopsis, Chamaemespilus, and Mespilus were not considered distinct and more research is needed to determine the taxonomic status of Rhaphiolepis from Eriobotrya. Within the core Maleae, five groups were revealed, whereas Sorbus L. was split as its members belonged to different groups.
Identification and variation analysis of the composition and content of essential oil and fragrance compounds in Phoebe zhennan wood at different tree ages
Authors: Yang Hanbo , Zhang Shuaiying , Gu Yunjie , Peng Jian , Huang Xin , Guo Hongying , Chen Lianghua , Jiang Yongze , Liu Minhao , Luo Xiandan , Xie Jiaxin , Wan Xueqin
Published: March 2024

Wood essential oil and wood products with special fragrances are high value-added forest products. Despite the availability of essential oil and volatile organic compounds (VOCs) from Phoebe zhennan wood, their variation and dependence on tree age have not been examined. After essential oil extraction and wood processing, the yields and compositions of essential oils and VOCs in wood from P. zhennan trees of different ages (10a, 30a, and 80a) were determined. The yield of essential oil from 30a wood was significantly greater than that from 10a and 80a wood. Liquid chromatography–mass spectrometry (LC−MS) and gas chromatography−mass spectrometry (GC−MS) revealed 672 and 41 volatile compounds, respectively, in the essential oil and wood, the majority of which exhibited large fluctuations in relative content and composition depending on tree age. Sesquiterpenoids, fatty acids and conjugates may greatly contribute to the main components of essential oil from wood. Almost all major sesquiterpenoid compounds, such as caryophyllene α-oxide, eudesmo, and cubebene, were identified in the essential oils from the 30a and 80a wood, and their relative contents were much greater than those in the 10a wood. The main components of the wood fragrance were sesquiterpenoids. The types and relative contents of sesquiterpenoids from wood increased with tree age. These results suggest that choosing wood from trees of a suitable age will significantly improve the efficiency of wood utilization.
Saudi women STEM pioneers: penetrating the mud ceiling
Authors: Alghamdi Amani K. H. , Almazroa Hiya
Published: March 2024

Although researchers actively study women’s experiences in STEM fields, few do so from women’s perspective. We thematically analyzed life narrative semi-structured interview data (46-item open-ended instrument, 90–120 Min) from eight STEM pioneering Saudi Arabian women careerists (mathematics, medicine, and biology) (convenience sample summer 2023). The objective was to glean their insights to discern self-reported influences (internal and external), struggles, and challenges in launching and advancing their careers. The extremely accomplished participants (all married, most with children) averaged age 65+, had 40+ years of experience and came from the three largest Saudi provinces. Important factors influencing choosing STEM included personality traits (e.g., deep desire to academically succeed; problem focused); secondary school peer/academic learning experiences; and male family member support, especially fathers. Struggles and challenges (often viewed as opportunities) included the mud (not glass) ceiling; male colleagues’ harsh, prejudiced treatment; and unsupportive administration. Participants were research driven and willing to relocate, re-educate, and change direction to establish and advance their careers. Implications for future research and policy initiatives are woven into the discussion and recommendations.
Aerobic capacity and mitochondrial function in bipolar disorder: a longitudinal study during acute phases and after clinical remission
Authors: Giménez-Palomo Anna , Guitart-Mampel Mariona , Roqué Gemma , Sánchez Ester , Borràs Roger , Meseguer Ana , García-García Francesc Josep , Tobías Esther , Valls-Roca Laura , Anmella Gerard , Valentí Marc , Olivier Luis , de Juan Oscar , Ochandiano Iñaki , Andreu Helena , Radua Joaquim , Verdolini Norma , Berk Michael , Vieta Eduard , Garrabou Glòria , Roca Josep , Alsina-Restoy Xavier , Pacchiarotti Isabella
Published: March 2024

Background

Aerobic capacity has shown to predict physical and mental health-related quality of life in bipolar disorder (BD). However, the correlation between exercise respiratory capacity and mitochondrial function remains understudied. We aimed to assess longitudinally intra-individual differences in these factors during mood episodes and remission in BD.

Methods

This study included eight BD patients admitted to an acute psychiatric unit. Incremental cardiopulmonary exercise test (CPET) was conducted during acute episodes (T0), followed by constant work rate cycle ergometry (CWRCE) to evaluate endurance time, oxygen uptake at peak exercise (VO2peak) and at the anaerobic threshold. The second test was repeated during remission (T1). Mitochondrial respiration rates were assessed at T0 and T1 in peripheral blood mononuclear cells.

Results

Endurance time, VO2peak, and anaerobic threshold oxygen consumption showed no significant variations between T0 and T1. Basal oxygen consumption at T1 tended to inversely correlate with maximal mitochondrial respiratory capacity (r=-0.690, p=0.058), and VO2peak during exercise at T1 inversely correlated with basal and minimum mitochondrial respiration (r=-0.810, p=0.015; r=-0.786, p=0.021, respectively).

Conclusions

Our preliminary data showed that lower basal oxygen consumption may be linked to greater mitochondrial respiratory capacity, and maximum oxygen uptake during the exercise task was associated with lower basal mitochondrial respiration, suggesting that lower oxygen requirements could be associated with greater mitochondrial capacity. These findings should be replicated in larger samples stratified for manic and depressive states.