bluuebunny/crossref_metadata_2025 huggingface dataset:
Classic and new strategies for the treatment of advanced melanoma and non-melanoma skin cancer
Authors: Rubatto Marco , Sciamarrelli Nadia , Borriello Silvia , Pala Valentina , Mastorino Luca , Tonella Luca , Ribero Simone , Quaglino Pietro
Published: February 2023

Advanced melanoma and non-melanoma skin cancers (NMSCs) are burdened with a dismal prognosis. To improve the survival of these patients, studies on immunotherapy and target therapies in melanoma and NMSCs are rapidly increasing. BRAF and MEK inhibitors improve clinical outcomes, and anti-PD1 therapy demonstrates better results than chemotherapy or anti-CTLA4 therapy in terms of the survival of patients with advanced melanoma. In recent years, the combination therapy of nivolumab plus ipilimumab has gained ground in studies for its survival and response rate benefits in patients with advanced melanoma. In addition, neoadjuvant treatment for stages III and IV melanoma, either as monotherapy or combination therapy, has recently been discussed. Another promising strategy evaluated in recent studies is the triple combination of anti-PD-1/PD-L1 immunotherapy and anti-BRAF plus anti-MEK targeted therapy. On the contrary, in advanced and metastatic BCC, successful therapeutic strategies, such as vismodegib and sonidegib, are based on the inhibition of aberrant activation of the Hedgehog signaling pathway. In these patients, anti-PD-1 therapy with cemiplimab should be reserved as the second-line therapy in case of disease progression or poor response. In patients with locally advanced or metastatic SCC, who are not candidates for surgery or radiotherapy, anti-PD1 agents such as cemiplimab, pembrolizumab, and cosibelimab (CK-301) have shown significant results in terms of response rate. PD-1/PD-L1 inhibitors, such as avelumab, have also been used in Merkel carcinoma, achieving responses in half of the patients with advanced disease. The latest prospect emerging for MCC is the locoregional approach involving the injection of drugs that can stimulate the immune system. Two of the most promising molecules used in combination with immunotherapy are cavrotolimod (a Toll-like receptor 9 agonist) and a Toll-like receptor 7/8 agonist. Another area of study is cellular immunotherapy with natural killer cells stimulated with an IL-15 analog or CD4/CD8 cells stimulated with tumor neoantigens. Neoadjuvant treatment with cemiplimab in CSCCs and nivolumab in MCCs has shown promising results. Despite the successes of these new drugs, the new challenges ahead will be to select patients who will benefit from these treatments based on biomarkers and parameters of the tumor microenvironment.
Metagenomic next-generation sequencing for the etiological diagnosis of rabies virus in cerebrospinal fluid
Authors: Liu Yong , Mo Xichao , Feng Ye , Willoughby Rodney E. , Weng Xing , Wang Yuyang , Li Xing , Gao Junling , Tian Jinfei , Peng Jie
Published: February 2023

Background

Rabies is a highly fatal disease. Once symptoms develop, death usually occurs within days. Survivors were occasionally reported in the literatures. Ante-mortem diagnosis remains a challenge in most rabies endemic countries. A novel, accurate diagnostic assay is highly desirable.

Methods

We used metagenomic next-generation sequencing (mNGS) to examine the cerebrospinal fluid (CSF) samples of a 49-year-old patient with rabies and validated the results by TaqMan PCR and RT-PCR/Sanger sequencing.

Results

Metagenomic next-generation sequencing identified sequence reads uniquely aligned to the rabies virus (RABV). PCR confirmed the presence of the partial RABV N gene in the CSF. Phylogenetic analysis showed that the RABV grouped as an Asian clade, which is the most broadly distributed clade in China.

Conclusion

Metagenomic next-generation sequencing may be a useful screening tool for the etiological diagnosis of rabies, especially in the absence of timely rabies laboratory testing or in patients with no exposure history.
Establishment and application of multiplex real-time PCR for simultaneous detection of four viruses associated with porcine reproductive failure
Authors: Chen Yuan , Luo Shile , Tan Jianmei , Zhang Luhua , Qiu Shengwu , Hao Zhiyou , Wang Naidong , Deng Zhibang , Wang Aibing , Yang Qing , Yang Yi , Wang Changjian , Zhan Yang
Published: February 2023

Many pathogens cause reproductive failure in sows suffering a broad spectrum of sequelae, including abortions, stillbirth, mummification, embryonic death, and infertility. Although various detection methods, such as polymerase chain reaction (PCR) and real-time PCR, have been widely used for molecular diagnosis, mainly for a single pathogen. In this study, we developed a multiplex real-time PCR method for the simultaneous detection of porcine circovirus type 2 (PCV2), porcine circovirus type 3 (PCV3), porcine parvovirus (PPV) and pseudorabies virus (PRV) associated with porcine reproductive failure. The R2 values for the standard curve of multiplex real-time PCR of PCV2, PCV3, PPV, and PRV reached to 0.996, 0.997, 0.996, and 0.998, respectively. Importantly, the limit of detection (LoD) of PCV2, PCV3, PPV, and PRV, were 1, 10, 10, 10 copies/reaction, respectively. Meanwhile, specificity test results indicated that multiplex real-time PCR for simultaneous detection is specific for these four target pathogens and does not react with other pathogens, such as classical swine fever virus, porcine reproductive and respiratory syndrome virus, and porcine epidemic diarrhea virus. Besides, this method had good repeatability with coefficients of variation of intra- and inter-assay less than 2%. Finally, this approach was further evaluated by 315 clinical samples for its practicality in the field. The positive rates of PCV2, PCV3, PPV, and PRV were 66.67% (210/315), 8.57% (27/315), 8.89% (28/315), and 4.13% (13/315), respectively. The overall co-infection rates of two or more pathogens were 13.65% (43/315). Therefore, this multiplex real-time PCR provides an accurate and sensitive method for the identification of those four underlying DNA viruses among potential pathogenic agents, allowing it to be applied in diagnostics, surveillance, and epidemiology.
Infection dynamics, transmission, and evolution after an outbreak of porcine reproductive and respiratory syndrome virus
Authors: Clilverd Hepzibar , Martín-Valls Gerard , Li Yanli , Martín Marga , Cortey Martí , Mateu Enric
Published: February 2023

The present study was aimed at describing the infection dynamics, transmission, and evolution of porcine reproductive and respiratory syndrome virus (PRRSV) after an outbreak in a 300-sow farrow-to-wean farm that was implementing a vaccination program. Three subsequent batches of piglets (9–11 litters/batch) were followed 1.5 (Batch 1), 8 (Batch 2), and 12 months after (Batch 3) from birth to 9 weeks of age. The RT-qPCR analysis showed that shortly after the outbreak (Batch 1), one third of sows were delivering infected piglets and the cumulative incidence reached 80% by 9 weeks of age. In contrast, in Batch 2, only 10% animals in total got infected in the same period. In Batch 3, 60% litters had born-infected animals and cumulative incidence rose to 78%. Higher viral genetic diversity was observed in Batch 1, with 4 viral clades circulating, of which 3 could be traced to vertical transmission events, suggesting the existence of founder viral variants. In Batch 3 though only one variant was found, distinguishable from those circulating previously, suggesting that a selection process had occurred. ELISA antibodies at 2 weeks of age were significantly higher in Batch 1 and 3 compared to Batch 2, while low levels of neutralizing antibodies were detected in either piglets or sows in all batches. In addition, some sows present in Batch 1 and 3 delivered infected piglets twice, and the offspring were devoid of neutralizing antibodies at 2 weeks of age. These results suggest that a high viral diversity was featured at the initial outbreak followed by a phase of limited circulation, but subsequently an escape variant emerged in the population causing a rebound of vertical transmission. The presence of unresponsive sows that had vertical transmission events could have contributed to the transmission. Moreover, the records of contacts between animals and the phylogenetic analyses allowed to trace back 87 and 47% of the transmission chains in Batch 1 and 3, respectively. Most animals transmitted the infection to 1–3 pen-mates, but super-spreaders were also identified. One animal that was born-viremic and persisted as viremic for the whole study period did not contribute to transmission.
Escherichia coli CspA stimulates translation in the cold of its own mRNA by promoting ribosome progression
Authors: Giuliodori Anna Maria , Belardinelli Riccardo , Duval Melodie , Garofalo Raffaella , Schenckbecher Emma , Hauryliuk Vasili , Ennifar Eric , Marzi Stefano
Published: February 2023

Escherichia coli CspA is an RNA binding protein that accumulates during cold-shock and stimulates translation of several mRNAs—including its own. Translation in the cold of cspA mRNA involves a cis-acting thermosensor element, which enhances ribosome binding, and the trans-acting action of CspA. Using reconstituted translation systems and probing experiments we show that, at low temperature, CspA specifically promotes the translation of the cspA mRNA folded in the conformation less accessible to the ribosome, which is formed at 37°C but is retained upon cold shock. CspA interacts with its mRNA without inducing large structural rearrangements, but allowing the progression of the ribosomes during the transition from translation initiation to translation elongation. A similar structure-dependent mechanism may be responsible for the CspA-dependent translation stimulation observed with other probed mRNAs, for which the transition to the elongation phase is progressively facilitated during cold acclimation with the accumulation of CspA.
Detection and identification of fungi in the lower airway of children with and without cystic fibrosis
Authors: O’Connor John B. , Wagner Brandie D. , Harris J. Kirk , Frank Daniel N. , Clabots Diana E. , Laguna Theresa A.
Published: February 2023

Introduction

Airway infection and inflammation lead to the progression of obstructive lung disease in persons with cystic fibrosis (PWCF). However, cystic fibrosis (CF) fungal communities, known drivers of CF pathophysiology, remain poorly understood due to the shortcomings of traditional fungal culture. Our objective was to apply a novel small subunit rRNA gene (SSU-rRNA) sequencing approach to characterize the lower airway mycobiome in children with and without CF.

Methods

Bronchoalveolar lavage fluid (BALF) samples and relevant clinical data were collected from pediatric PWCF and disease control (DC) subjects. Total fungal load (TFL) was measured using quantitative PCR, and SSU-rRNA sequencing was used for mycobiome characterization. Results were compared across groups, and Morisita-Horn clustering was performed.

Results

161 (84%) of the BALF samples collected had sufficient load for SSU-rRNA sequencing, with amplification being more common in PWCF. BALF from PWCF had increased TFL and increased neutrophilic inflammation compared to DC subjects. PWCF exhibited increased abundance of Aspergillus and Candida, while Malassezia, Cladosporium, and Pleosporales were prevalent in both groups. CF and DC samples showed no clear differences in clustering when compared to each other or to negative controls. SSU-rRNA sequencing was used to profile the mycobiome in pediatric PWCF and DC subjects. Notable differences were observed between the groups, including the abundance of Aspergillus and Candida.

Discussion

Fungal DNA detected in the airway could represent a combination of pathogenic fungi and environmental exposure (e.g., dust) to fungus indicative of a common background signature. Next steps will require comparisons to airway bacterial communities.
Whole body-electromyostimulation effects on serum biomarkers, physical performances and fatigue in Parkinson’s patients: A randomized controlled trial
Authors: di Cagno Alessandra , Buonsenso Andrea , Centorbi Marco , Manni Luigi , Di Costanzo Alfonso , Casazza Giusy , Parisi Attilio , Guerra Germano , Calcagno Giuseppe , Iuliano Enzo , Soligo Marzia , Fiorilli Giovanni ,   for The WB-EMS Parkinson’s Group
Published: February 2023

Background

Whole-body electromyostimulation (WB-EMS) was never previously applied to Parkinson’s disease (PD) patients. This randomized controlled study aimed to find the most effective and safe WB-EMS training protocol for this population.

Methods

Twenty-four subjects (age: 72.13 ± 6.20 years), were randomly assigned to three groups: a high-frequency WB-EMS strength training group (HFG) (rectangular stimulation at 85 Hz, 350 μs, 4 s stimulation/4 s rest), a low-frequency WB-EMS aerobic training group (LFG) (rectangular stimulation 7 Hz, 350 μs, with a continuous pulse duration), and an inactive control group (CG). Participants of the two experimental groups underwent 24 controlled WB-EMS training sessions, with a duration of 20 min each, during 12-week intervention. Serum growth factors (BDNF, FGF-21, NGF and proNGF), α-synuclein, physical performance and Parkinson’s Disease Fatigue Scale (PFS-16) responses were analyzed to evaluate the pre-post variation and differences among groups.

Results

Significant interactions of Time*Groups were detected for BDNF (Time*Groups p = 0.024; Time*CG, b = −628, IC95% = −1,082/−174, p = 0.008), FGF-21 (Time*Groups p = 0.009; Time*LFG b = 1,346, IC95% = 423/2268, p = 0.005), and α-synuclein (Time*Groups p = 0.019; Time*LFG b = −1,572, IC95% = −2,952/−192, p = 0.026). Post hoc analyses and comparisons of ΔS (post–pre), performed independently for each group, showed that LFG increased serum BDNF levels (+ 203 pg/ml) and decreased α-synuclein levels (−1,703 pg/ml), while HFG showed the opposite effects (BDNF: −500 pg/ml; α-synuclein: + 1,413 pg/ml). CG showed a significant BDNF reduction over time. Both LFG and HFG showed significant improvements in several physical performance outcomes and the LFG showed better results than HFG. Concerning PFS-16, significant differences over time (b = −0.4, IC95% = −0.8/−0.0, p = 0.046) and among groups (among all groups p < 0.001) were found, and the LFG exhibited better results than the HFG (b = −1.0, IC95% = −1.3/−0.7, p < 0.001), and CG (b = −1.7, IC95% = −2.0/−1.4, p < 0.001) with this last one that worsened over time.

Conclusion

LFG training was the best choice for improving or maintaining physical performance, fatigue perception and variation in serum biomarkers.

Clinical trial registration

https://www.clinicaltrials.gov/ct2/show/NCT04878679, identifier NCT04878679.
Design of a SMA-based soft composite structure for wearable rehabilitation gloves
Authors: Xie Qiaolian , Meng Qiaoling , Yu Wenwei , Wu Zhiyu , Xu Rongna , Zeng Qingxin , Zhou Zhongchao , Yang Tianyi , Yu Hongliu
Published: February 2023

The combination of smart soft composite structure based shape memory alloy (SMA) and exoskeleton technology has the advantages of light weight, energy saving, and great human-exoskeleton interaction. However, there are no relevant studies on the application of SMA-based soft composite structure (SSCS) in hand exoskeletons. The main difficulty is that directional mechanical properties of SSCS need to comply with fingers movement, and SSCS can deliver enough output torque and displacement to the relevant joints. This paper aims to study the application of SSCS for wearable rehabilitation gloves and explore its bionic driving mechanism. This paper proposes a soft wearable glove (Glove-SSCS) for hand rehabilitation actuated by the SSCS, based on finger force analysis under different drive modes. The Glove-SSCS can support five-finger flexion and extension, weighs only 120 g, and adopts modular design. Each drive module adopts a soft composite structure. And the structure integrates actuation, sensing and execution, including an active layer (SMA spring), a passive layer (manganese steel sheet), a sensing layer (bending sensor) and connection layers. To obtain a high-performance SMA actuators, the performance of SMA materials was tested in terms of temperature and voltage, temperature at the shortest length, pre-tensile length and load. And the human-exoskeleton coupling model of Glove-SSCS is established and analyzed from force and motion. The results show that the Glove-SSCS can realize bidirectional movements of fingers flexion and extension, with ranges of motion are 90–110° and 30–40°, and their cycles are 13–19 s and 11–13 s. During the use of Glove-SSCS, the temperature of gloves is from 25 to 67°C, and the surface temperature of hands is from 32 to 36°C. The temperature of Glove-SSCS can be kept at the lowest temperature of SMA operation without much impact on the human body.
Vanadium improves memory and spatial learning and protects the pyramidal cells of the hippocampus in juvenile hydrocephalic mice
Authors: Femi-Akinlosotu Omowumi Moromoke , Olopade Funmilayo Eniola , Obiako Jane , Olopade James Olukayode , Shokunbi Matthew Temitayo
Published: February 2023

Background

Hydrocephalus is a neurological condition known to cause learning and memory disabilities due to its damaging effect on the hippocampal neurons, especially pyramidal neurons. Vanadium at low doses has been observed to improve learning and memory abilities in neurological disorders but it is uncertain whether such protection will be provided in hydrocephalus. We investigated the morphology of hippocampal pyramidal neurons and neurobehavior in vanadium-treated and control juvenile hydrocephalic mice.

Methods

Hydrocephalus was induced by intra-cisternal injection of sterile-kaolin into juvenile mice which were then allocated into 4 groups of 10 pups each, with one group serving as an untreated hydrocephalic control while others were treated with 0.15, 0.3 and 3 mg/kg i.p of vanadium compound respectively, starting 7 days post-induction for 28 days. Non-hydrocephalic sham controls (n = 10) were sham operated without any treatment. Mice were weighed before dosing and sacrifice. Y-maze, Morris Water Maze and Novel Object Recognition tests were carried out before the sacrifice, the brains harvested, and processed for Cresyl Violet and immunohistochemistry for neurons (NeuN) and astrocytes (GFAP). The pyramidal neurons of the CA1 and CA3 regions of the hippocampus were assessed qualitatively and quantitatively. Data were analyzed using GraphPad prism 8.

Results

Escape latencies of vanadium-treated groups were significantly shorter (45.30 ± 26.30 s, 46.50 ± 26.35 s, 42.99 ± 18.44 s) than untreated group (62.06 ± 24.02 s) suggesting improvements in learning abilities. Time spent in the correct quadrant was significantly shorter in the untreated group (21.19 ± 4.15 s) compared to control (34.15 ± 9.44 s) and 3 mg/kg vanadium-treated group (34.35 ± 9.74 s). Recognition index and mean % alternation were lowest in untreated group (p = 0.0431, p=0.0158) suggesting memory impairments, with insignificant improvements in vanadium-treated groups. NeuN immuno-stained CA1 revealed loss of apical dendrites of the pyramidal cells in untreated hydrocephalus group relative to control and a gradual reversal attempt in the vanadium-treated groups. Astrocytic activation (GFAP stain) in the untreated hydrocephalus group were attenuated in the vanadium-treated groups under the GFAP stain. Pyknotic index in CA1 pyramidal layer of untreated (18.82 ± 2.59) and 0.15mg/kg vanadium-treated groups (18.14 ± 5.92) were significantly higher than control (11.11 ± 0.93; p = 0.0205, p = 0.0373) while there was no significant difference in CA3 pyknotic index across all groups.

Conclusion

Our results suggest that vanadium has a dose-dependent protective effect on the pyramidal cells of the hippocampus and on memory and spatial learning functions in juvenile hydrocephalic mice.
Functional imaging of the exposed brain
Authors: Soloukey Sadaf , Vincent Arnaud J. P. E. , Smits Marion , De Zeeuw Chris I. , Koekkoek Sebastiaan K. E. , Dirven Clemens M. F. , Kruizinga Pieter
Published: February 2023

When the brain is exposed, such as after a craniotomy in neurosurgical procedures, we are provided with the unique opportunity for real-time imaging of brain functionality. Real-time functional maps of the exposed brain are vital to ensuring safe and effective navigation during these neurosurgical procedures. However, current neurosurgical practice has yet to fully harness this potential as it pre-dominantly relies on inherently limited techniques such as electrical stimulation to provide functional feedback to guide surgical decision-making. A wealth of especially experimental imaging techniques show unique potential to improve intra-operative decision-making and neurosurgical safety, and as an added bonus, improve our fundamental neuroscientific understanding of human brain function. In this review we compare and contrast close to twenty candidate imaging techniques based on their underlying biological substrate, technical characteristics and ability to meet clinical constraints such as compatibility with surgical workflow. Our review gives insight into the interplay between technical parameters such sampling method, data rate and a technique’s real-time imaging potential in the operating room. By the end of the review, the reader will understand why new, real-time volumetric imaging techniques such as functional Ultrasound (fUS) and functional Photoacoustic Computed Tomography (fPACT) hold great clinical potential for procedures in especially highly eloquent areas, despite the higher data rates involved. Finally, we will highlight the neuroscientific perspective on the exposed brain. While different neurosurgical procedures ask for different functional maps to navigate surgical territories, neuroscience potentially benefits from all these maps. In the surgical context we can uniquely combine healthy volunteer studies, lesion studies and even reversible lesion studies in in the same individual. Ultimately, individual cases will build a greater understanding of human brain function in general, which in turn will improve neurosurgeons’ future navigational efforts.
Synergistic effects of psyllium husk powder and different levels of methylcellulose on the storage stability of sodium caseinate emulsion
Authors: Fu Qing-quan , Zhou Lei , Shi Hai-bo , Wang Rong-rong , Yang Lin-wei
Published: February 2023

The study investigated the effects of compound fibers composed of psyllium husk powder (PHP, 0.3%) and methylcellulose (MC, 0, 0.3, 0.6, 0.9, and 1.2%) on the storage stability, rheology, and microstructure of sodium caseinate emulsions. Results showed that the emulsion stability was enhanced with the increased concentrations of MC, especially at the concentration of 1.2%. The oil droplet size in the emulsions was decreased as the concentrations of compound fibers increased, which was further confirmed by the optical microscope analysis. The rheological measurements and cryo-scanning electron microscopy results indicated that compound fibers improved the viscosity of the emulsions, and formed a strong three-dimensional network structure. The results of confocal laser scanning microscope and surface protein concentration measurements showed that compound fibers were evenly distributed into the oil droplet surface. The above results demonstrate that compound fibers are an effective thickener and emulsifier in enhancing the stability properties of oil-in-water (O/W) emulsions stabilized by sodium caseinate.
Impact of dielectric barrier discharge cold plasma on the lipid oxidation, color stability, and protein structures of myoglobin-added washed pork muscle
Authors: Wang Xiaoting , Wang Jin , Wang Zhaobin , Yan Wenjing , Zhuang Hong , Zhang Jianhao
Published: February 2023

Cold plasma has been considered a novel non-thermal processing technique and attracted a high attention by the food industry. In this study, the influences of dielectric barrier discharge cold plasma (DBD-CP) on the myoglobin (Mb)-added washed pork muscle (WPM) were evaluated. The electrophoresis pattern, autoxidation, and secondary structure of Mb were analyzed. The results found that DBD-CP caused the decrease of the redness and total sulfhydryl (T-SH) in WPM, while the increase of non-heme, peroxide value (PV), and thiobarbituric acid reactive substances (TBARS), suggested that treatment triggered protein oxidation and heme degradation. Additionally, DBD-CP treatment enhanced the autoxidation of Mb, induced the release of intact heme from the globin, rearranged the charged groups, and promoted Mb aggregation. The transformation of α-helix into the random coil of Mb demonstrated that DBD-CP weakened the tensile strength. Overall, data indicated that DBD-CP promoted autoxidation and changed the secondary structure of Mb, accelerating Mb-mediated lipid oxidation in WPM. Thus, further studies about the optimization of processing conditions by DBD-CP need to be performed.
Effective oxygen metabolism-based prognostic signature for colorectal cancer
Authors: Yuan Yonghui , Zhang Zhong-guo , Ma Bin , Ji Pengfei , Ma Shiyang , Qi Xun
Published: February 2023

Backgroud

Oxygen metabolism is an important factor affecting the development of tumors, but its roles and clinical value in Colorectal cancer are not clear. We developed an oxygen metabolism (OM) based prognostic risk model for colorectal cancer and explored the role of OM genes in cancer.

Methods

Gene expression and clinical data obtained from The Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium databases were consider as discovery and validation cohort, respectively. The prognostic model based on differently expressed OM genes between tumor and GTEx normal colorectal tissues were constructed in discovery cohort and validated in validation cohort. The Cox proportional hazards analysis was used to test clinical independent. Upstream and downstream regulatory relationships and interaction molecules are used to clarify the roles of prognostic OM genes in colorectal cancer.

Results

A total of 72 common differently expressed OM genes were detected in the discovery and validation set. A five-OM gene prognostic model including LRT2, ATP6V0E2, ODC1, SEL1L3 and VDR was established and validated. Risk score determined by the model was an independent prognostic according to routine clinical factors. Besides, the role of prognostic OM genes involves transcriptional regulation of MYC and STAT3, and downstream cell stress and inflammatory response pathways.

Conclusions

We developed a five-OM gene prognostic model and study the unique roles of oxygen metabolism in of colorectal cancer
Case Report: Pancreatic metastasis of renal cell carcinoma 16 years after nephrectomy
Authors: Lou Yidan , Guo Kaibo , Zheng Song
Published: February 2023

Background

Renal cell carcinoma (RCC) is the most common renal malignancy, and may metastasize to different sites in the body via hematogenous and lymphomatous routes. The pancreas is a rare metastatic site of metastatic RCC (mRCC) and isolated pancreatic metastasis of RCC (isPMRCC) is even rarer.

Results

The present report describes a case of isPMRCC that recurred 16 years after surgery. The patient responded well to the treatment with pancreaticoduodenectomy and systemic therapy, and no recurrence was recorded after 2 years.

Conclusions

isPMRCC is a distinct subgroup of RCC with unique clinical characteristics that may be explained by its underlying molecular mechanisms. Surgery and systemic therapy confer survival benefits to patients with isPMRCCs, although the recurrence problem has to be paid attention to.
Construction of targeted 10B delivery agents and their uptake in gastric and pancreatic cancer cells
Authors: Wang Song , Zhang Zhengchao , Miao Lele , Zhang Jiaxing , Tang Futian , Teng Muzhou , Li Yumin
Published: February 2023

Boron Neutron Capture Therapy (BNCT) is a new binary radiation therapy for tumor tissue, which kills tumor cells with neutron capture reaction. Boron neutron capture therapy has become a technical means for glioma, melanoma, and other diseases has been included in the clinical backup program. However, BNCT is faced with the key problem of developing and innovating more efficient boron delivery agents to solve the targeting and selectivity. We constructed a tyrosine kinase inhibitor-L-p-boronophenylalanine (TKI-BPA) molecule, aiming to improve the selectivity of boron delivery agents by conjugating targeted drugs while increasing the molecular solubility by adding hydrophilic groups. It shows excellent selectivity in differential uptake of cells, and its solubility is more than 6 times higher than BPA, leading to the saving of boron delivery agents. This modification method is effective for improving the efficiency of the boron delivery agent and is expected to become a potential alternative with high clinical application value.
Adjuvant effect of herbal medicine on transarterial chemoembolization in patients with hepatocellular carcinoma: A systematic review and meta-analysis
Authors: Oh Hyeon-Muk , Kim Eun-Ji , Bae Hye-Ri , Cho Jung-Hyo , Son Chang-Gue , Lee Nam-Hun
Published: February 2023

Objectives

Primary hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, especially in Asian countries. As a practical treatment option, transarterial chemoembolization (TACE) has been well applied; however, its limited efficacy remains challenging. This study analyzed the adjuvant effects of herbal medicine on TACE to determine whether it improves clinical outcomes in patients with HCC.

Methods

A systematic review and meta-analysis was performed to compare the adjuvant effects of herbal medicine on TACE versus TACE therapy alone. We searched the literature from eight databases since January 2011.

Results

Twenty-five studies involving 2,623 participants were selected. The adjuvant therapy of herbal medicine on TACE improved the overall survival at 0.5 years (OR = 1.70; 95% CI 1.21-2.38), 1 year (OR = 2.01; 95% CI 1.65-2.46), 2 years (OR = 1.83; 95% CI 1.20-2.80), and 3 years (OR = 1.90; 95% CI 1.25-2.91). The combination therapy also increased the tumor response rate (OR = 1.84; 95% CI 1.40-2.42).

Conclusions

Despite the unsatisfactory quality of the included studies, the adjuvant therapy of herbal medicine on TACE may provide survival benefits to patients with HCC.

Systematic reviews registration

http://www.crd.york.ac.uk/PROSPERO, identifier (376691).
CD203c is expressed by human fetal hepatoblasts and distinguishes subsets of hepatoblastoma
Authors: Muench Marcus O. , Fomin Marina E. , Gutierrez Alan G. , López-Terrada Dolores , Gilfanova Renata , Nosworthy Christopher , Beyer Ashley I. , Ostolaza Gregory , Kats Dina , Matlock Kevin L. , Cairo Stefano , Keller Charles
Published: February 2023

Background & Aims

Hepatocytic cells found during prenatal development have unique features compared to their adult counterparts, and are believed to be the precursors of pediatric hepatoblastoma. The cell-surface phenotype of hepatoblasts and hepatoblastoma cell lines was evaluated to discover new markers of these cells and gain insight into the development of hepatocytic cells and the phenotypes and origins of hepatoblastoma.

Methods

Human midgestation livers and four pediatric hepatoblastoma cell lines were screened using flow cytometry. Expression of over 300 antigens was evaluated on hepatoblasts defined by their expression of CD326 (EpCAM) and CD14. Also analyzed were hematopoietic cells, expressing CD45, and liver sinusoidal-endothelial cells (LSECs), expressing CD14 but lacking CD45 expression. Select antigens were further examined by fluorescence immunomicroscopy of fetal liver sections. Antigen expression was also confirmed on cultured cells by both methods. Gene expression analysis by liver cells, 6 hepatoblastoma cell lines, and hepatoblastoma cells was performed. Immunohistochemistry was used to evaluate CD203c, CD326, and cytokeratin-19 expression on three hepatoblastoma tumors.

Results

Antibody screening identified many cell surface markers commonly or divergently expressed by hematopoietic cells, LSECs, and hepatoblasts. Thirteen novel markers expressed on fetal hepatoblasts were identified including ectonucleotide pyrophosphatase/phosphodiesterase family member 3 (ENPP-3/CD203c), which was found to be expressed by hepatoblasts with widespread expression in the parenchyma of the fetal liver. In culture CD203c+CD326++ cells resembled hepatocytic cells with coexpression of albumin and cytokeratin-19 confirming a hepatoblast phenotype. CD203c expression declined rapidly in culture whereas the loss of CD326 was not as pronounced. CD203c and CD326 were co-expressed on a subset of hepatoblastoma cell lines and hepatoblastomas with an embryonal pattern.

Conclusions

CD203c is expressed on hepatoblasts and may play a role in purinergic signaling in the developing liver. Hepatoblastoma cell lines were found to consist of two broad phenotypes consisting of a cholangiocyte-like phenotype that expressed CD203c and CD326 and a hepatocyte-like phenotype with diminished expression of these markers. CD203c was expressed by some hepatoblastoma tumors and may represent a marker of a less differentiated embryonal component.
Bioaccumulation and biotransformation of simvastatin in probiotic bacteria: A step towards better understanding of drug-bile acids-microbiome interactions
Authors: Đanić Maja , Pavlović Nebojša , Lazarević Slavica , Stanimirov Bojan , Vukmirović Saša , Al-Salami Hani , Mooranian Armin , Mikov Momir
Published: February 2023

Introduction: Although pharmacogenetics and pharmacogenomics have been at the forefront of research aimed at finding novel personalized therapies, the focus of research has recently extended to the potential of intestinal microbiota to affect drug efficacy. Complex interplay of gut microbiota with bile acids may have significant repercussions on drug pharmacokinetics. However, far too little attention has been paid to the potential implication of gut microbiota and bile acids in simvastatin response which is characterized by large interindividual variations.

The Aim: In order to gain more insight into the underlying mechanism and its contribution in assessing the clinical outcome, the aim of our study was to examine simvastatin bioaccumulation and biotransformation in probiotic bacteria and the effect of bile acids on simvastatin bioaccumulation in in vitro conditions.

Materials and methods: Samples with simvastatin, probiotic bacteria and three different bile acids were incubated at anaerobic conditions at 37°C for 24 h. Extracellular and intracellular medium samples were collected and prepared for the LC-MS analysis at predetermined time points (0 min, 15 min, 1 h, 2 h, 4 h, 6 h, 24 h). The concentrations of simvastatin were analyzed by LC-MS/MS. Potential biotransformation pathways were analyzed using a bioinformatics approach in correlation with experimental assay.

Results: During the incubation, simvastatin was transported into bacteria cells leading to a drug bioaccumulation over the time, which was augmented upon addition of bile acids after 24 h. A decrease of total drug level during the incubation indicates that the drug is partly biotransformed by bacterial enzymes. According to the results of bioinformatics analysis, the lactone ring is the most susceptible to metabolic changes and the most likely reactions include ester hydrolysis followed by hydroxylation.

Conclusion: Results of our study reveal that bioaccumulation and biotransformation of simvastatin by intestinal bacteria might be the underlying mechanisms of altered simvastatin bioavailability and therapeutic effect. Since this study is based only on selected bacterial strains in vitro, further more in-depth research is needed in order to elicit completely the contribution of complex drug-microbiota-bile acids interactions to overall clinical response of simvastatin which could ultimately lead to novel approaches for the personalized lipid-lowering therapy.
Aerodynamic effect of an alula-like vortex generator using pressure sensitive paint technique
Authors: Chung Ping-Han , Yeh Szu-I
Published: February 2023

Herein, the pressure-sensitive paint (PSP) was used to quantitatively investigate the aerodynamic effect of an alula-like vortex generator, which is a bio-inspired passive flow control structure. The global pressure distributions on the upper surface at different angles of attack were measured to determine the strength of sectional suction forces on the wing. An alula-like vortex generator equipped at the leading edge of the wing enlarged the area of the suction region (negative pressure coefficient) on the upper surface in both the streamwise and spanwise directions under near-stall and deep-stall conditions, which is related to the generation of lift and avoiding the stall of wing. A wing model equipped with a vortex generator of an 11% height/chord length ratio exhibited the greatest performance at all angles of attack. In this study, the use of PSP technique not only helps to understand the aerodynamic effect of the alula-like vortex generator but also shows a perspective tool for bio-inspired MAVs design.
Field recommended concentrations of pyraclostrobin exposure disturb the development and immune response of worker bees (Apis mellifera L.) larvae and pupae
Authors: Xiong Manqiong , Qin Gan , Wang Lizhu , Wang Ruyi , Zhou Ruiqi , Luo Xiaotian , Lou Qun , Huang Shaokang , Li Jianghong , Duan Xinle
Published: February 2023

The strobilurin fungicide pyraclostrobin is widely used to prevent and control the fungal diseases of various nectar and pollen plants. Honeybees also directly or indirectly contact this fungicide with a long-term exposure period. However, the effects of pyraclostrobin on the development and physiology of Apis mellifera larvae and pupae during continuous exposure have been rarely known. To investigate the effects of field-realistic concentrations of pyraclostrobin on honeybee survival and development, the 2-day-old larvae were continuously fed with different pyraclostrobin solutions (100 mg/L and 83.3 mg/L), and the expression of development-, nutrient-, and immune-related genes in larvae and pupae were examined. The results showed that two field-realistic concentrations of pyraclostrobin (100 and 83.3 mg/L) significantly decreased the survival and capped rate of larvae, the weight of pupae and newly emerged adults, and such decrease was a positive correlation to the treatment concentrations. qPCR results showed that pyraclostrobin could induce the expression of Usp, ILP2, Vg, Defensin1, and Hymenoptaecin, decrease the expression of Hex100, Apidaecin, and Abaecin in larvae, could increase the expression of Ecr, Usp, Hex70b, Vg, Apidaecin, and Hymenoptaecin, and decreased the expression of ILP1, Hex100 and Defensin1in pupae. These results reflect pyraclostrobin could decrease nutrient metabolism, immune competence and seriously affect the development of honeybees. It should be used cautiously in agricultural practices, especially in the process of bee pollination.
Drought stress prediction and propagation using time series modeling on multimodal plant image sequences
Authors: Das Choudhury Sruti , Saha Sinjoy , Samal Ashok , Mazis Anastasios , Awada Tala
Published: February 2023

The paper introduces two novel algorithms for predicting and propagating drought stress in plants using image sequences captured by cameras in two modalities, i.e., visible light and hyperspectral. The first algorithm, VisStressPredict, computes a time series of holistic phenotypes, e.g., height, biomass, and size, by analyzing image sequences captured by a visible light camera at discrete time intervals and then adapts dynamic time warping (DTW), a technique for measuring similarity between temporal sequences for dynamic phenotypic analysis, to predict the onset of drought stress. The second algorithm, HyperStressPropagateNet, leverages a deep neural network for temporal stress propagation using hyperspectral imagery. It uses a convolutional neural network to classify the reflectance spectra at individual pixels as either stressed or unstressed to determine the temporal propagation of stress in the plant. A very high correlation between the soil water content, and the percentage of the plant under stress as computed by HyperStressPropagateNet on a given day demonstrates its efficacy. Although VisStressPredict and HyperStressPropagateNet fundamentally differ in their goals and hence in the input image sequences and underlying approaches, the onset of stress as predicted by stress factor curves computed by VisStressPredict correlates extremely well with the day of appearance of stress pixels in the plants as computed by HyperStressPropagateNet. The two algorithms are evaluated on a dataset of image sequences of cotton plants captured in a high throughput plant phenotyping platform. The algorithms may be generalized to any plant species to study the effect of abiotic stresses on sustainable agriculture practices.
Digital democracy: A systematic literature review
Authors: Congge Umar , Guillamón María-Dolores , Nurmandi Achmad , Salahudin  , Sihidi Iradhad Taqwa
Published: February 2023

Digital democracy provides a new space for community involvement in democratic life. This study aims to conduct a systematic literature review to uncover the trend of concepts in the study of digital democracy. This study used descriptive analysis with data sources derived from the Scopus database from the period between 2014 and 2020 (a total of 230 articles) and processed with VOSviewer. The results showed three dominant concepts, namely democracy, the internet, and movement. In addition, it was found that the digital era provides positive and negative impacts on democracy, that public knowledge in a quality digital democracy is important, and that there is strong elite control in virtual democracy. The results of this research can be used as a basis for developing digital democracy studies. Meanwhile, this study was limited by the fact that the articles reviewed were only sourced from Scopus and did not include publications from 2022. Therefore, future studies need to take a comparative analysis approach that uses the Web of Science (WoS) database and increases the time period in which articles are sourced.
The relationship between transmission misinformation, COVID-19 stress and satisfaction with life among adults
Authors: Nguyen Phuong Thi Hang , Van Huynh Son , Nguyen Nhi Ngoc Yen , Le Tran Bao , Le Pha Cam , Nantachai Gallayaporn , Tran-Chi Vinh-Long
Published: February 2023

The perplexing evolution of the COVID-19 pandemic has had a significant effect on the spiritual lives of Vietnamese people in general, and particularly adults. The objective of this study was to ascertain the link between adult satisfaction with life and COVID-19 stress in Vietnam and investigate if COVID-19 transmission disinformation modifies the effect of COVID-19 stress on adult satisfaction with life. A total of 435 Vietnamese adults were enrolled online to finish answering, including the Satisfaction with Life Scale (SL), the COVID-19 Stress Scale (CS), and the COVID-19 Transmission Misinformation Scale (CTMS), consisting of 350 females and 85 males. Correlation, regression, and basic mediation analyses were used to dissociate the data. According to the findings of our study, there is a difference in gender in satisfaction with life. Females have a greater degree of satisfaction with life than males. Significant differences exist between relatives of direct and indirect COVID-19 transmission misinformation workers. People who had relatives who were frontline medical staff had higher COVID-19 Transmission Misinformation than others. There is a positive correlation between satisfaction with life and COVID-19 spreading disinformation, but it can have adverse effects on persons’ physical health. Additionally, COVID-19 transmission misinformation has a role in the relationship between COVID-19 stress and adult life satisfaction. Individuals are more likely to access misinformation about COVID-19 transmission, which results in enhanced life satisfaction. During the COVID-19 epidemic, adults in Vietnam should be aware of the damaging consequences of COVID-19 transmission misinformation on their stress levels. Stress may significantly influence not just one’s mental health but also other aspects of one’s life. Clinicians should be aware of COVID-19 transmission misinformation and stress, which affect psychological treatment.
The Qatar 2022 World Cup warm-up: Football goal-scoring evolution in the last 14 FIFA World Cups (1966–2018)
Authors: Mićović Branimir , Leontijević Bojan , Dopsaj Milivoj , Janković Aleksandar , Milanović Zoran , Garcia Ramos Amador
Published: February 2023

The aim of this study was to elucidate pattern of attacking actions leading up to goal scoring during the 14 FIFA World Cups from 1966 to 2018. The study analysed 1881 goals scored during a total of 732 matches. We employed observational methodology design. Before goal analysis began, it was developed the observing protocol in which data related to selected variables, by system of notation, was entered after reviewing each individual goal scoring action. The analysis of all video material was carried out independently by four experienced examiners (three of them are Ph.D in sports science and one is Ph.D. candidate in sports science with at least 7 years of coaching and experience as analyst in football). The inter-and intra-observer reliability presented good level of agreement. The kappa values ranged from 0.82 (goal scoring through open play) to 1.00 (action leading up to goal), showing a very high agreement for all performance variables. Interclass correlation was very high (ICC = 0.966, 95% upper and lower confidence intervals were between 0.933 and 1.00). A statistically significant trend (p < 0.05) from 1966 to 2018 was identified towards a higher relative frequency of goals scored from set play and collective actions from open play. The Chi-square did not reveal significant differences in the frequency of goal scoring patterns and goal-scoring zones. The results also revealed that the majority of goals were scored between the 76th and 90th minutes of a match (22.7%), from open play (70.5%), inside the penalty area (54.7%), one touch finishing (62.5%), and collective attacks in open play (55.8%). These findings may provide a possible strategic direction for improving goal-scoring performance in football, as well as practical implementation in World Cup tournament preparation.