bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction of a heat-resistant strain of Lentinus edodes by fungal Hsp20 protein overexpression and genetic transformation
Authors: Ling Yun-Yan , Ling Zhi-Lin , Zhao Rui-Lin
Published: November 2022

The shiitake mushroom (Lentinus edodes) is the second most popular edible mushroom globally due to its rich nutritional value and health benefits associated with consumption. However, the characteristics of growing at low temperatures limit the area and time of its cultivating. We selected a low-temperature cultivar as the original strain. We proposed to construct a heat-shock protein expression vector to achieve genetic transformation in this low-temperature strain to improve the survivability of the strain against the heat-shock response. In this study, an overexpression vector pEHg-gdp-hsp20 for the heat shock protein 20 gene of A. bisporus was constructed using a homologous recombination method. This vector was transferred into dikaryotic and monokaryotic mycelia by the Agrobacterium tumefaciens-method. The integration of hygb and hsp20 into the genome of L. edodes mycelia was verified by growth experiments on resistant plates and PCR analysis. The expression of the reporter gene mgfp5 was verified by fluorescence microscopy analysis and statistically resulted in 18.52 and 26.39% positivity for dikaryon, and monokaryon, respectively. Real-time PCR analysis showed that the expression of the hsp20 gene was more than 10-fold up-regulated in the three transformants; the mycelia of the three overexpression transformants could resume growth after 24 h heat treatment at 40°C, but the mycelia of the starting strain L087 could not recover growth at 25°C indicating that strains that successfully expressed hsp20 had greater overall recovery after heat shock. According to the study, A. bisporus hsp20 gene overexpression effectively improves the defensive capability of low-temperature mushroom strains against heat shock, laying the foundation for breeding heat-resistant high-quality transgenic shiitake mushrooms.
Histopathological and immunological characteristics of placentas infected with chikungunya virus
Authors: Salomão Natália , Rabelo Kíssila , Avvad-Portari Elyzabeth , Basílio-de-Oliveira Carlos , Basílio-de-Oliveira Rodrigo , Ferreira Fátima , Ferreira Luiz , de Souza Thiara Manuele , Nunes Priscila , Lima Monique , Sales Anna Paula , Fernandes Regina , de Souza Luiz José , Dias Laura , Brasil Patrícia , dos Santos Flavia , Paes Marciano
Published: November 2022

Although vertical transmission of CHIKV has been reported, little is known about the role of placenta in the transmission of this virus and the effects of infection on the maternal-fetal interface. In this work we investigated five placentas from pregnant women who became infected during the gestational period. Four formalin-fixed paraffin-embedded samples of placenta (cases 1–4) were positive for CHIKV by RT-PCR. One (case 5) had no positive test of placenta, but had positive RT-PCR for CHIKV in the serum of the mother and the baby, confirming vertical transmission. The placentas were analyzed regarding histopathological and immunological aspects. The main histopathological changes were: deciduitis, villous edema, deposits, villous necrosis, dystrophic calcification, thrombosis and stem vessel obliteration. In infected placentas we noted increase of cells (CD8+ and CD163+) and pro- (IFN-γ and TNF-α) and anti-inflammatory (TGF-β and IL-10) cytokines compared to control placentas. Moreover, CHIKV antigen was detected in decidual cell, trophoblastic cells, stroma villi, Hofbauer cells, and endothelial cells. In conclusion, CHIKV infection seems to disrupt placental homeostasis leading to histopathological alterations in addition to increase in cellularity and cytokines overproduction, evidencing an altered and harmful environment to the pregnant woman and fetus.
Genomic reconstruction and features of glycosylation pathways in the apicomplexan Cryptosporidium parasites
Authors: Wang Dongqiang , Wang Chenchen , Zhu Guan
Published: November 2022

Cryptosporidium is a genus of apicomplexan parasites infecting humans or other vertebrates. The majority of the Cryptosporidium species live in host intestines (e.g., C. parvum, C. hominis and C. ubiquitum), but there are a few gastric species (e.g., C. muris and C. andersoni). Among them, C. parvum is the most important zoonotic species, for which a number of glycoproteins have been reported for being involved in the interacting with host cells. However, little is known on the cryptosporidium glycobiology. Information on the glycosylation pathways in Cryptosporidium parasites remains sketchy and only a few studies have truly determined the glycoforms in the parasites. Here we reanalyzed the Cryptosporidium genomes and reconstructed the glycosylation pathways, including the synthesis of N- and O-linked glycans and GPI-anchors. In N-glycosylation, intestinal Cryptosporidium possesses enzymes to make a simple precursor with two terminal glucoses on the long arm (i.e., Glc2Man5GlcNAc2 vs. Glc3Man9GlcNAc2 in humans), but gastric species only makes a simpler precursor containing only the “core” structure (i.e., Man3GlcNAc2). There is an ortholog of glucosidase II (GANAB) in all Cryptosporidium species, for which the authenticity is questioned because it contains no signal peptide and exist in gastric species lacking terminal glucoses for the enzyme to act on. In O-linked glycosylation, all Cryptosporidium species may attach one-unit HexNAc (GalNAc and GlcNAc) and two-unit Fuc-type (Man-Fuc) glycans to the target proteins. Cryptosporidium lacks enzymes to further process N- and O-glycans in the Golgi. The glycosylphosphatidylinositol (GPI)-anchor in Cryptosporidium is predicted to be unbranched and unprocessed further in the Golgi. Cryptosporidium can synthesize limited nucleotide sugars, but possesses at least 12 transporters to scavenge nucleotide sugars or transport them across the ER/Golgi membranes. Overall, Cryptosporidium makes much simpler glycans than the hosts, and the N-glycoforms further differ between intestinal and gastric species. The Cryptosporidium N- and O-glycans are neutrally charged and have limited capacity to absorb water molecules in comparison to the host intestinal mucins that are negatively charged and highly expandable in waters.
Comprehensive analysis of dysregulated circular RNAs and construction of a ceRNA network involved in the pathology of Alzheimer’s disease in a 5 × FAD mouse model
Authors: Sun Ting , Zeng Li , Cai Zhongdi , Liu Qingshan , Li Zhuorong , Liu Rui
Published: November 2022

Introduction

Alzheimer’s disease (AD) causes a decline in cognitive function that poses a significant hazard to human health. However, the exact pathogenesis of AD and effective treatment have both proven elusive. Circular RNAs (circRNAs), which were initially deemed as meaningless non-coding RNAs, have been shown to participate in a variety of physiological and pathological processes. However, the variations and characteristics of circRNAs are not fairly well understood during the occurrence and development of AD.

Methods

In this study, we performed RNA sequencing analyses, identified circRNA expression profiles, and explored the circRNA-associated competing endogenous RNA (ceRNA) relationship in the hippocampus of five familial AD (5 × FAD) mice with cognitive dysfunction.

Results

The RNA sequencing results identified 34 dysregulated circRNAs in the hippocampus of 5 × FAD mice, including 17 upregulated and 17 downregulated circRNAs. The circRNA-miRNA interaction network for the dysregulated circRNAs was generated, and it was found to include 34 circRNAs and 711 miRNAs. Next, 2067 mRNAs potentially modulated by upregulated circRNA-interacting miRNAs and 2297 mRNAs potentially modulated by downregulated circRNA-interacting miRNAs were identified. Pathway enrichment analyses revealed that the circRNA-miRNA-mRNA network modulated AD development via multiple pathways, such as axon guidance, mitogen-activated protein kinase, and neurotrophin. The associated biological processes were mainly related to neuron projection development, cell morphogenesis, and head development. Their corresponding distributions were especially high in the axon, postsynapse, and neuronal body. We constructed a ceRNA network that included five circRNAs, four miRNAs, and 188 mRNAs. In this network, the differential expressions of three circRNAs (circRNA04655, circRNA00723, and circRNA01891), two miRNAs (miR-3470b and miR-6240), and 13 mRNAs (Vgll3, Nhsl2, Rab7, Tardbp, Vps33b, Fam107a, Tacr1, Ankrd40, Creb1, Snap23, Csnk1a1, Bmi1, and Bfar) in the hippocampus of 5 × FAD mice using qRT-PCR analyses were consistent with the RNA sequencing results. Another one circRNAs (circRNA00747) and two mRNAs (Zfp37 and Polr1e) had similar expression trends to the sequencing data, while circRNA03723 and Mapk10 had deviated expression trends to the sequencing data.

Conclusions

In conclusion, our study uncovered dysregulated circRNA expression profiles in the hippocampus of 5 × FAD mice, stretched comprehension of ceRNA biology, investigated the potential role of this ceRNA network in pathogenesis and progression, and identified potential biomarkers and therapeutic targets for AD.
Advanced aging effects on implicit motor imagery and its links to motor performance: An investigation via mental rotation of letters, hands, and feet
Authors: Muto Hiroyuki , Suzuki Maki , Sekiyama Kaoru
Published: November 2022

This study focuses on changes in implicit motor imagery during advanced aging and these changes’ co-occurrences with physical motor deficits. We administered a mental rotation (MR) task with letters, hands, and feet to 28 young adults (20–27 years) and to 71 older adults (60–87 years), and assessed motor skills (gait mobility and hand dexterity) and neuropsychological performance. Compared to young adults, older adults showed lower MR performance for all stimuli and stronger biomechanical constraint effects on both hand and foot rotation. Moreover, the foot biomechanical constraint effect continued to increase during late adulthood, and declines in hand and foot motor imagery emerged at earlier old ages than declines in visual imagery. These results first demonstrated distinct aging trajectories of hand motor imagery, foot motor imagery, and visual imagery. Exploratory partial correlation analysis for older adults showed positive associations of low-level perceptual-motor skills (Trail Making Test-A performance) with hand and foot MR performance and positive associations of mobility (Timed Up and Go test performance) with foot and letter MR performance. These associations exhibited somewhat different patterns from those of young adults and raised the possibility that age-related declines in motor (and visual) imagery co-occur with declines in motor functioning.
Application and prospects of somatic cell reprogramming technology for spinal cord injury treatment
Authors: Yang Riyun , Pan Jingying , Wang Yankai , Xia Panhui , Tai Mingliang , Jiang Zhihao , Chen Gang
Published: November 2022

Spinal cord injury (SCI) is a serious neurological trauma that is challenging to treat. After SCI, many neurons in the injured area die due to necrosis or apoptosis, and astrocytes, oligodendrocytes, microglia and other non-neuronal cells become dysfunctional, hindering the repair of the injured spinal cord. Corrective surgery and biological, physical and pharmacological therapies are commonly used treatment modalities for SCI; however, no current therapeutic strategies can achieve complete recovery. Somatic cell reprogramming is a promising technology that has gradually become a feasible therapeutic approach for repairing the injured spinal cord. This revolutionary technology can reprogram fibroblasts, astrocytes, NG2 cells and neural progenitor cells into neurons or oligodendrocytes for spinal cord repair. In this review, we provide an overview of the transcription factors, genes, microRNAs (miRNAs), small molecules and combinations of these factors that can mediate somatic cell reprogramming to repair the injured spinal cord. Although many challenges and questions related to this technique remain, we believe that the beneficial effect of somatic cell reprogramming provides new ideas for achieving functional recovery after SCI and a direction for the development of treatments for SCI.
Voltage-gated sodium channels in diabetic sensory neuropathy: Function, modulation, and therapeutic potential
Authors: Bigsby Stephanie , Neapetung Joseph , Campanucci Verónica A.
Published: November 2022

Voltage-gated sodium channels (NaV) are the main contributors to action potential generation and essential players in establishing neuronal excitability. NaV channels have been widely studied in pain pathologies, including those that develop during diabetes. Diabetic sensory neuropathy (DSN) is one of the most common complications of the disease. DSN is the result of sensory nerve damage by the hyperglycemic state, resulting in a number of debilitating symptoms that have a significant negative impact in the quality of life of diabetic patients. Among those symptoms are tingling and numbness of hands and feet, as well as exacerbated pain responses to noxious and non-noxious stimuli. DSN is also a major contributor to the development of diabetic foot, which may lead to lower limb amputations in long-term diabetic patients. Unfortunately, current treatments fail to reverse or successfully manage DSN. In the current review we provide an updated report on NaV channels including structure/function and contribution to DSN. Furthermore, we summarize current research on the therapeutic potential of targeting NaV channels in pain pathologies, including DSN.
EEG hybrid brain-computer interfaces: A scoping review applying an existing hybrid-BCI taxonomy and considerations for pediatric applications
Authors: Mussi Matheus G. , Adams Kim D.
Published: November 2022

Most hybrid brain-computer interfaces (hBCI) aim at improving the performance of single-input BCI. Many combinations are possible to configure an hBCI, such as using multiple brain input signals, different stimuli or more than one input system. Multiple studies have been done since 2010 where such interfaces have been tested and analyzed. Results and conclusions are promising but little has been discussed as to what is the best approach for the pediatric population, should they use hBCI as an assistive technology. Children might face greater challenges when using BCI and might benefit from less complex interfaces. Hence, in this scoping review we included 42 papers that developed hBCI systems for the purpose of control of assistive devices or communication software, and we analyzed them through the lenses of potential use in clinical settings and for children. We extracted taxonomic categories proposed in previous studies to describe the types of interfaces that have been developed. We also proposed interface characteristics that could be observed in different hBCI, such as type of target, number of targets and number of steps before selection. Then, we discussed how each of the extracted characteristics could influence the overall complexity of the system and what might be the best options for applications for children. Effectiveness and efficiency were also collected and included in the analysis. We concluded that the least complex hBCI interfaces might involve having a brain inputs and an external input, with a sequential role of operation, and visual stimuli. Those interfaces might also use a minimal number of targets of the strobic type, with one or two steps before the final selection. We hope this review can be used as a guideline for future hBCI developments and as an incentive to the design of interfaces that can also serve children who have motor impairments.
Dissociation of categorical and coordinate spatial relations on dynamic network organization states
Authors: Hao Xin , Chen Zhencai , Huang Taicheng , Song Yiying , Kong Xiangzhen , Liu Jia
Published: November 2022

Humans can flexibly represent both categorical and coordinate spatial relations. Previous research has mainly focused on hemisphere lateralization in representing these two types of spatial relations, but little is known about how distinct network organization states support representations of the two. Here we used dynamic resting-state functional connectivity (FC) to explore this question. To do this, we separated a meta-identified navigation network into a ventral and two other subnetworks. We revealed a Weak State and a Strong State within the ventral subnetwork and a Negative State and a Positive State between the ventral and other subnetworks. Further, we found the Weak State (i.e., weak but positive FC) within the ventral subnetwork was related to the ability of categorical relation recognition, suggesting that the representation of categorical spatial relations was related to weak integration among focal regions in the navigation network. In contrast, the Negative State (i.e., negative FC) between the ventral and other subnetworks was associated with the ability of coordinate relation processing, suggesting that the representation of coordinate spatial relations may require competitive interactions among widely distributed regions. In sum, our study provides the first empirical evidence revealing different focal and distributed organizations of the navigation network in representing different types of spatial information.
Human nasal olfactory stem cells, purified as advanced therapy medicinal products, improve neuronal differentiation
Authors: Jaloux Charlotte , Bonnet Maxime , Vogtensperger Marie , Witters Marie , Veran Julie , Giraudo Laurent , Sabatier Florence , Michel Justin , Legré Regis , Guiraudie-Capraz Gaëlle , Féron François
Published: November 2022

Background

Olfactory ecto-mesenchymal stem cells (OE-MSC) are mesenchymal stem cells derived from the lamina propria of the nasal mucosa. They display neurogenic and immunomodulatory properties and were shown to induce recovery in animal models of spinal cord trauma, hearing loss, Parkinsons’s disease, amnesia, and peripheral nerve injury. As a step toward clinical practice, we sought to (i) devise a culture protocol that meets the requirements set by human health agencies and (ii) assess the efficacy of stem cells on neuron differentiation.

Methods

Nasal olfactory mucosa biopsies from three donors were used to design and validate the good manufacturing process for purifying stem cells. All processes and procedures were performed by expert staff from the cell therapy laboratory of the public hospital of Marseille (AP-HM), according to aseptic handling manipulations. Premises, materials and air were kept clean at all times to avoid cross-contamination, accidents, or even fatalities. Purified stem cells were cultivated for 24 or 48 h and conditioned media were collected before being added to the culture medium of the neuroblastoma cell line Neuro2a.

Results

Compared to the explant culture-based protocol, enzymatic digestion provides higher cell numbers more rapidly and is less prone to contamination. The use of platelet lysate in place of fetal calf serum is effective in promoting higher cell proliferation (the percentage of CFU-F progenitors is 15.5%), with the optimal percentage of platelet lysate being 10%. Cultured OE-MSCs do not show chromosomal rearrangement and, as expected, express the usual phenotypic markers of mesenchymal stem cells. When incorporated in standard culture medium, the conditioned medium of purified OE-MSCs promotes cell differentiation of Neuro2a neuroblastoma cells.

Conclusion

We developed a safer and more efficient manufacturing process for clinical grade olfactory stem cells. With this protocol, human OE-MSCs will soon be used in a Phase I clinical based on their autologous transplantation in digital nerves with a neglected injury. However, further studies are required to unveil the underlying mechanisms of action.
An objective bone conduction verification tool using a piezoelectric thin-film force transducer
Authors: Nie Yafei , Sang Jinqiu , Zheng Chengshi , Xu Jian , Zhang Fangjie , Li Xiaodong
Published: November 2022

All hearing aid fittings should be validated with appropriate outcome measurements, whereas there is a lack of well-designed objective verification methods for bone conduction (BC) hearing aids, compared to the real-ear measurement for air conduction hearing aids. This study aims to develop a new objective verification method for BC hearing aids by placing a piezoelectric thin-film force transducer between the BC transducer and the stimulation position. The newly proposed method was compared with the ear canal method and the artificial mastoid method through audibility estimation. The audibility estimation adopted the responses from the transducers that correspond to the individual BC hearing thresholds and three different input levels of pink noise. Twenty hearing-impaired (HI) subjects without prior experience with hearing aids were recruited for this study. The measurement and analysis results showed that the force transducer and ear canal methods almost yielded consistent results, while the artificial mastoid method exhibited significant differences from these two methods. The proposed force transducer method showed a lower noise level and was less affected by the sound field signal when compared with other methods. This indicates that it is promising to utilize a piezoelectric thin-film force transducer as an in-situ objective measurement method of BC stimulation.
Mini review of research requirements for radioactive waste management including disposal
Authors: Grambow Bernd
Published: November 2022

This brief overview of research needs related to radioactive waste management and disposal is intended to provide a framework for addressing some important research questions related to historical developments and some large industrial mega-projects for geological disposal of radioactive waste that are currently being developed. Considering that the level of industrial development varies considerably between countries, research in this field of knowledge has a strong international and long-term orientation, encompassing both basic and applied research, including optimisation.
Fish oil and probiotics supplementation through milk chocolate improves spatial learning and memory in male Wistar rats
Authors: Faccinetto-Beltrán Paulinna , Aguirre-López Luis Octavio , Bañuelos-Pineda Jacinto , Reza-Zaldívar Edwin E. , Santacruz Arlette , Hernández-Brenes Carmen , Pérez-Carrillo Esther , Jacobo-Velázquez Daniel A.
Published: November 2022

Background

Cognition and brain function is critical through childhood and should be improved with balanced diets. Incorporating bioactive ingredients such as omega-3 polyunsaturated fatty acids (ω3 PUFAs) and probiotics into food formulations could be used as an approach to improve cognitive function. This study evaluated the effects on cognitive capacity of complementing rodent diets with chocolate, by itself and in combination with ω3 PUFAs from fish oil and probiotics.

Methods

Spatial learning and memory in the rats were determined by the Barnes maze test in short- and long-term memory. Samples from the cecum were obtained to assess microbial counts (Lactobacillus, Bifidobacterium, Enterobacteriaceae, and total bacteria), and brains were recovered to analyze the neural morphology of the tissues. Also, glucose, brain weights, and epididymal tissue were analyzed.

Results

The combination of chocolate with fish oil and probiotics improved the memory of rats compared to the result of each bioactive compound when evaluated separately. Treatments did not affect sugar level, epididymal adipose tissue, or brain weight. On the other hand, consuming probiotics alone or in combination with chocolate decreased Enterobacteria counts, while Lactobacillus and Bifidobacteria counts were not affected. Neural morphological analysis showed that combining chocolate with probiotics and ω3 PUFAs increased the number of neurons in the hippocampal CA1 and CA3 regions.

Conclusion

Chocolate added with probiotics and ω3 PUFAs improved spatial memory and learning in the studied model.
Optimization of ultrasound-assisted extraction of phenolics from Asparagopsis taxiformis with deep eutectic solvent and their characterization by ultra-high-performance liquid chromatography-mass spectrometry
Authors: Gao Heqi , Wang Yuxi , Guo Zhiqiang , Liu Yuxin , Wu Qian , Xiao Juan
Published: November 2022

Asparagopsis taxiformis is a significant source of phenolics. Owing to the incessant demand of green extraction procedures for phenolics from A. taxiformis, ultrasound-assisted extraction (UAE) using deep eutectic solvents (DESs) was optimized. Among the tested DESs, betaine-levulinic acid afforded the highest total phenolic content (TPC). Moreover, the optimal extraction conditions elucidated from single-factor and response surface methodologies comprised a 52.41°C ultrasonic temperature, 46.48% water content of DES, and 26.99 ml/g liquid-to-solid ratio. The corresponding TPC (56.27 mg GAE/100 g DW) and antioxidant ability fitted the predicted values. UAE afforded superior TPC and antioxidant abilities with DESs than with traditional solvents. Using UHPLC-MS, seven phenolic acids, 18 flavonoids, and two bromophenols were identified and quantified. DES-UAE afforded the highest phenolic compound number (26) and sum of contents. These results disclose the high extraction efficiency of DES-UAE for A. taxiformis phenolics and provide a basis for the higher-value application of this species.
The association between obesity and vitamin D deficiency modifies the progression of kidney disease after ischemia/reperfusion injury
Authors: Bernardo Desiree Rita Denelle , Canale Daniele , Nascimento Mariana Moura , Shimizu Maria Heloisa Massola , Seguro Antonio Carlos , de Bragança Ana Carolina , Volpini Rildo Aparecido
Published: November 2022

Acute kidney injury (AKI) alters renal hemodynamics, leading to tubular injury, activating pathways of inflammation, proliferation, and cell death. The initial damage caused to renal tissue after an ischemia/reperfusion (I/R) injury exerts an important role in the pathogenesis of the course of AKI, as well as in the predisposition to chronic kidney disease. Vitamin D deficiency has been considered a risk factor for kidney disease and it is associated with tubulointerstitial damage, contributing to the progression of kidney disease. Obesity is directly related to diabetes mellitus and hypertension, the main metabolic disorders responsible for the progression of kidney disease. Furthermore, the expansion of adipose tissue is described as an important factor for increased secretion of pro-inflammatory cytokines and their respective influence on the progression of kidney disease. We aimed to investigate the influence of vitamin D deficiency and obesity on the progression of renal disease in a murine model of renal I/R. Male Wistar rats underwent renal I/R surgery on day 45 and followed until day 90 of the protocol. We allocated the animals to four groups according to each diet received: standard (SD), vitamin D-depleted (VDD), high fat (HFD), or high fat vitamin D-depleted (HFDV). At the end of 90 days, we observed almost undetectable levels of vitamin D in the VDD and HFDV groups. In addition, HFD and HFDV groups presented alterations in the anthropometric and metabolic profile. The combination of vitamin D deficiency and obesity contributed to alterations of functional and hemodynamic parameters observed in the HFDV group. Moreover, this combination favored the exacerbation of the inflammatory process and the renal expression of extracellular matrix proteins and phenotypic alteration markers, resulting in an enlargement of the tubulointerstitial compartment. All these changes were associated with an increased renal expression of transforming growth factor β and reduced expression of the vitamin D receptor. Our results show that the synergistic effect of obesity and vitamin D deficiency exacerbated the hemodynamic and morphological changes present in the evolution of renal disease induced by I/R.
Circulating tumor DNA mutation profile is associated with the prognosis and treatment response of Chinese patients with newly diagnosed diffuse large B-cell lymphoma
Authors: Guan Tao , Zhang Min , Liu Xiaolan , Li Jing , Xin Beibei , Ren Yanxin , Yang Yuchao , Wang Hui , Zhao Mengjing , Huang Yunpeng , Guo Xiaojing , Du Jun , Qian Wenbin , Su Liping
Published: November 2022

Background

Characterization of gene mutation profiles can provide new treatment options for patients with diffuse large B-cell lymphoma (DLBCL). However, this method is challenged by the limited source of tissue specimens, especially those of DLBCL patients at advanced stages. Therefore, in the current study, we aimed to describe the gene mutation landscape of DLBCL using circulating tumor DNA (ctDNA) samples obtained from patients’ blood samples, as well as to explore the relationship between ctDNA mutations and the prognosis and treatment response of patients with newly diagnosed DLBCL.

Methods

A total of 169 newly diagnosed Chinese DLBCL patients were included in this study, among which 85 patients were divided into a training set and 84 were assigned into a validation set. The mutation profile of a 59-gene panel was analyzed by targeted next generation sequencing (NGS) of the patients’ ctDNA samples. Differences in clinical factors between patients with and without ctDNA mutations were analyzed. In addition, we also explored gene mutation frequencies between GCB and non-GCB subtypes, and the relationship between gene mutation status, clinical factors, mean VAF (variant allele frequencies) and the patients’ overall survival (OS) and progression-free survival (PFS).

Results

ctDNA mutations were detected in 64 (75.3%) patients of the training set and 67 (79.8%) patients of the validation set. The most commonly mutated genes in both sets were PCLO, PIM1, MYD88, TP53, KMT2D, CD79B, HIST1H1E and LRP1B, with mutation frequencies of >10%. Patients with detectable ctDNA mutations trended to present advanced Ann Arbor stages (III-IV), elevated LDH (lactate dehydrogenase) levels, shorter OS and PFS, and a lower complete response (CR) rate to the R-CHOP regimen compared with DLBCL patients without ctDNA mutations. In addition, mean VAF (≥4.94%) and PCLO mutations were associated with poor OS and PFS.

Conclusion

We investigated the ctDNA mutation landscape in Chinese patients with newly diagnosed DLBCL and found that ctDNA could reflect tumor burden and patients with detectable ctDNA mutations trended to have shorter OS and PFS and a lower CR rate.
Comparative analysis of dosimetry and predictive somatotype parameters of prone and supine whole-breast irradiation among Chinese women after breast-conserving surgery
Authors: Gao Yi , Wang Li , Bai Han , Pan Xiang , Li Lan , Chang Li , Xia Yaoxiong , Li Wenhui , Hou Yu
Published: November 2022

Purpose

Finding a better treatment position (prone or supine) for whole-breast irradiation for Chinese female patients diagnosed with breast cancer by identify the associations between predictive somatotype parameters and dosimetric gains.

Materials and methods

Two volumetric-modulated arc therapy (VMAT) plans were deployed for whole-breast irradiation in supine and prone position with a total dose of 50 Gy in 25 fractions. Dose-volume parameters were compared and analysed both in the target volume and organs at risk, and equivalent uniform dose-based figure-of-merit (fEUD) models were further used to quantitatively evaluate the overall merits of the two plans. Body shape parameters, including body mass index (BMI), body surface area (BSA), breast shape, cup size, bust size and chest size, were collected. Anatomic features such as the central heart distance (CHD) were measured on supine CT. Spearman’s correlation analysis, receiver operating characteristic (ROC) curve analysis, and the linear regression models were conducted.

Results

Doses to the heart and left anterior descending coronary artery (LADCA) are greater in left-sided breast cancer (BC) patients in the prone position than in the supine position, and the opposite was true for right-sided BC patients (p<0.001). 19 of 63 patients (5 left-sided and 14 right-sided BC) achieved greater benefit from the prone position according to the fEUD score. Right-sided BC patients with a bust size ≥92.25 cm, drop-type breasts and cup size ≥B are very likely to benefit from prone-position radiotherapy. The CHD is significantly positively associated with △fEUD among right-sided BC patients (rho=0.506, p=0.004). Using a cut-off point of 2.215, the CHD had 71.4% sensitivity and 81.2% specificity in predicting a successful prone plan.

Conclusions

Right-sided BC patients had better dosimetric gain in the prone position than left-sided BC patients. The CHD is an especially good and novel predictor that could help to select prone-benefitting right-sided BC patients.
Survival benefit of primary tumor resection for gastric cancer with liver metastasis: A propensity score-matched, population-based study
Authors: Wu Jiayan , Yu Jiandong , Chen Zhiping , Zhu Hongquan , Zhong Chengrui , Liang Yongling , Mai Ziyan , Lin Zejin , Wan Yunle , Li Guolin
Published: November 2022

Objectives

Gastric cancer with liver metastasis (GCLM) is highly aggressive and has a poor prognosis. This study aims to evaluate the survival benefit of primary tumor resection (PTR) for gastric cancer with liver metastasis.

Methods

Data on patients with GCLM was extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. A 1:1 propensity score matching (PSM) analysis was performed to minimize the heterogeneity between the PTR and no-PTR groups. The Kaplan–Meier method and Cox regression analysis were used to assess the impact of primary tumor resection (PTR) on overall survival (OS) and cause-specific survival (CSS).

Results

A total of 3,001 patients with GCLM were included, with 328 patients treated with primary tumor resection (PTR), whereas the other 2,673 patients were not. Patients with PTR had a significantly higher OS and CSS rate than those without PTR in unmatched and PSM cohorts. In an unmatched cohort, the median OS was 12.0 months (95% CI, 10 months to 14 months) for those who underwent PTR and 4 months (95% CI, 4 months to 5 months) for those without PTR; the median CSS for those who underwent PTR was 12.0 months (95% CI, 10 months to14 months) and 4 months (95% CI, 4 months to 5 months) for those without PTR, respectively. After PMS, the median OS was 12.0 months (95% CI, 10 months to 17 months) for those who underwent PTR and 7 months (95% CI, 5 months to 10 months) for those without PTR, respectively; the median CSS for those who underwent PTR was 12.0 months (95% CI, 11 months to 17 months) and 7 months (95% CI, 5 months to 8 months) for those without PTR, respectively. In addition, multivariate Cox analysis in the PSM cohort showed that PTR, age, degree of tumor differentiation, and chemotherapy were independent prognostic factors for OS and CSS in GCLM. Specifically, PTR was a significant protective factor for OS (HR: 0.427; 95% CI, 0.325 to 0.561, P <0.001) and CSS (HR: 0.419; 95% CI, 0.313 to 0.561, P <0.001).

Conclusion

Primary tumor resection improves the survival of gastric cancer patients with liver metastasis.
Study protocol for comparing the efficacy of left-open single-flap technique versus double-flap technique after proximal gastrectomy: A multicenter randomized controlled trial
Authors: Yang Qin Chuan , Wang Wei Dong , Mo Zhen Chang , Yue Chao , Zhou Hai Kun , Gao Rui Qi , Yu Juan , Dong Dan Hong , Liu Jin Qiang , Wei Jiang Peng , Yang Xi Sheng , Ji Gang , Li Xiao Hua
Published: November 2022

Background

Proximal gastrectomy has gradually gained more attention due to its superiority in retaining the function of part of the stomach. The inevitable loss of the antireflux barrier and postoperative complications resulting from proximal gastrectomy can severely affect the quality of life. Continuous improvements in digestive tract reconstruction after proximal gastrectomy have yielded the development of a variety of methods with antireflux functions. Recently, our center attempted the left-open single-flap technique and initiated a multicenter, prospective, randomized controlled trial for patients undergoing proximal gastrectomy to reduce the difficulty of surgical anastomosis and the incidence of perioperative complications compared with the double-flap technique. These findings will provide more evidence-based medical research for the development of clinical guidelines.

Methods/design

This study is a prospective, multicenter, randomized controlled clinical trial. We plan to recruit 250 patients who are eligible for proximal gastrectomy. After informed consent is obtained, patients will be randomly assigned to the trial group (left-open single-flap technique) and the control group (double-flap technique) in a 1:1 allocation ratio.

Discussion

Increasingly, clinical studies have focused on the improvement of reconstruction modalities after proximal gastrectomy. Among these methods, the double-flap technique is a clinically effective method. The purpose of this study is to establish a prospective randomized controlled trial to compare the efficacy of the left-open single-flap technique versus the double-flap technique after proximal gastrectomy, aiming to provide more evidence-based medical studies for digestive tract reconstruction in proximal gastrectomy.

Clinical Trial Registration

ClinicalTrials.gov, identifier [NCT05418920].
Case report: Treatment of metastatic dedifferentiated chondrosarcoma with pembrolizumab yields sustained complete response
Authors: Singh Amisha , Thorpe Steven W. , Darrow Morgan , Carr-Ascher Janai R.
Published: November 2022

Dedifferentiated chondrosarcomas (DDCS) are aggressive tumors with poor outcomes. Treatment of localized DDCS is primarily surgical, though most patients present with unresectable or metastatic disease. Systemic treatment options for advanced DDCS are limited, and the benefits of chemotherapy in this patient population remain controversial. Among other systemic therapy options, there is emerging clinical evidence to support the use of immunotherapy in patients with advanced DDCS. However, studies regarding the efficacy of immunotherapy in advanced DDCS are limited. Here, we present the case of a patient with metastatic, programmed death-ligand 1 (PD-L1)-positive DDCS treated with pembrolizumab who showed a sustained complete response for 24 months after initiation of therapy. To our knowledge, this case represents one of few documented cases of metastatic chondrosarcoma with sustained response to immunotherapy. The impressive response seen with PD-L1 inhibition in our patient indicates that immunotherapy is a successful treatment option in a subset of DDCS patients, and further investigation is needed to identify potential responders to immunotherapy.
Utilization of macrocyclic peptides to target protein-protein interactions in cancer
Authors: Yang Jiawen , Zhu Qiaoliang , Wu Yifan , Qu Xiaojuan , Liu Haixia , Jiang Biao , Ge Di , Song Xiaoling
Published: November 2022

Protein-protein interactions (PPIs) play vital roles in normal cellular processes. Dysregulated PPIs are involved in the process of various diseases, including cancer. Thus, these PPIs may serve as potential therapeutic targets in cancer treatment. However, despite rapid advances in small-molecule drugs and biologics, it is still hard to target PPIs, especially for those intracellular PPIs. Macrocyclic peptides have gained growing attention for their therapeutic properties in targeting dysregulated PPIs. Macrocyclic peptides have some unique features, such as moderate sizes, high selectivity, and high binding affinities, which make them good drug candidates. In addition, some oncology macrocyclic peptide drugs have been approved by the US Food and Drug Administration (FDA) for clinical use. Here, we reviewed the recent development of macrocyclic peptides in cancer treatment. The opportunities and challenges were also discussed to inspire new perspectives.
Aged garlic extract as a potential prophylactic to reduce the progression of endometriosis and associated pain burden
Authors: Redwood Emily , Lam Virginie , Takechi Ryusuke , Kerr Deborah Anne , Jackaman Connie , Sharif Arazu , Mamo John Charles Louis
Published: November 2022

Endometriosis is a complex and potentially debilitating condition that has major impact on quality of life. There is emerging evidence that biological compounds found in garlic (Allium sativum) may be effective for attenuating endometrial pain. Suggested mechanisms for efficacy include modulation of inflammation and potent antioxidant effects. Aged-garlic-extract (AGE) is a centuries old process describing ethanolic extracts of garlic bulbs for 12–20 months. The AGE formulation realised contains a complex array of stabilised biologics with significant immunomodulatory effects relevant to inflammatory conditions. This perspective article puts forward a hypothesis that AGE should be considered as a prophylactic to manage endometrial pain.
A case for genomic medicine in South African paediatric patients with neuromuscular disease
Authors: Raga Sharika V. , Wilmshurst Jo Madeleine , Smuts Izelle , Meldau Surita , Bardien Soraya , Schoonen Maryke , van der Westhuizen Francois Hendrikus
Published: November 2022

Paediatric neuromuscular diseases are under-recognised and under-diagnosed in Africa, especially those of genetic origin. This may be attributable to various factors, inclusive of socioeconomic barriers, high burden of communicable and non-communicable diseases, resource constraints, lack of expertise in specialised fields and paucity of genetic testing facilities and biobanks in the African population, making access to and interpretation of results more challenging. As new treatments become available that are effective for specific sub-phenotypes, it is even more important to confirm a genetic diagnosis for affected children to be eligible for drug trials and potential treatments. This perspective article aims to create awareness of the major neuromuscular diseases clinically diagnosed in the South African paediatric populations, as well as the current challenges and possible solutions. With this in mind, we introduce a multi-centred research platform (ICGNMD), which aims to address the limited knowledge on NMD aetiology and to improve genetic diagnostic capacities in South African and other African populations.
Capillary refill time in sepsis: A useful and easily accessible tool for evaluating perfusion in children
Authors: Lamprea Shirley , Fernández-Sarmiento Jaime , Barrera Sofía , Mora Alicia , Fernández-Sarta Juan Pablo , Acevedo Lorena
Published: November 2022

The international sepsis guidelines emphasize the importance of early identification along with the combined administration of fluids, antibiotics and vasopressors as essential steps in the treatment of septic shock in childhood. However, despite these recommendations, septic shock mortality continues to be very high, especially in countries with limited resources. Cardiovascular involvement is common and, in most cases, determines the outcomes. Early recognition of hemodynamic dysfunction, both in the macro and microcirculation, can help improve outcomes. Capillary refill time (CRT) is a useful, available and easily accessible tool at all levels of care. It is a clinical sign of capillary vasoconstriction due to an excessive sympathetic response which seeks to improve blood redistribution from the micro- to the macrocirculation. An important reason for functionally evaluating the microcirculation is that, in septic shock, the correction of macrocirculation variables is assumed to result in improved tissue perfusion. This has been termed “hemodynamic coherence.” However, this coherence often does not occur in advanced stages of the disease. Capillary refill time is useful in guiding fluid resuscitation and identifying more seriously affected sepsis patients. Several factors can affect its measurement, which should preferably be standardized and performed on the upper extremities. In this review, we seek to clarify a few common questions regarding CRT and guide its correct use in patients with sepsis.
Serine and glycine metabolism-related gene expression signature stratifies immune profiles of brain gliomas, and predicts prognosis and responses to immunotherapy
Authors: Chen Siliang , Zhang Shuxin , Feng Wentao , Li Junhong , Yuan Yunbo , Li Wenhao , Wang Zhihao , Yang Yuan , Liu Yanhui
Published: November 2022

Glioma is one of the most lethal cancers and causes more than 200,000 deaths every year. Immunotherapy was an inspiring therapy for multiple cancers but failed in glioma treatment. The importance of serine and glycine and their metabolism has been well-recognized in the physiology of immune cells and microenvironment in multiple cancers. However, their correlation with prognosis, immune cells, and immune microenvironment of glioma remains unclear. In this study, we investigated the relationships between the expression pattern of serine and glycine metabolism-related genes (SGMGs) and clinicopathological features, prognosis, and tumor microenvironment in glioma based on comprehensive analyses of multiple public datasets and our cohort. According to the expression of SGMGs, we conducted the consensus clustering analysis to stratify all patients into four clusters with remarkably distinctive clinicopathological features, prognosis, immune cell infiltration, and immune microenvironment. Subsequently, a serine and glycine metabolism-related genes signature (SGMRS) was constructed based on five critical SGMGs in glioma to stratify patients into SGMRS high- and low-risk groups and tested for its prognostic value. Higher SGMRS expressed genes associated with the synthesis of serine and glycine at higher levels and manifested poorer prognosis. Besides, we confirmed that SGMRS was an independent prognostic factor and constructed nomograms with satisfactory prognosis prediction performance based on SGMRS and other factors. Analyzing the relationship between SGMRS and immune landscape, we found that higher SGMRS correlated with ‘hotter’ immunological phenotype and more immune cell infiltration. Furthermore, the expression levels of multiple immunotherapy-related targets, including PD-1, PD-L1, and B7-H3, were positively correlated with SGMRS, which was validated by the better predicted response to immune checkpoint inhibitors. In conclusion, our study explored the relationships between the expression pattern of SGMGs and tumor features and created novel models to predict the prognosis of glioma patients. The correlation of SGMRS with immune cells and microenvironment in gliomas suggested an essential role of serine and glycine metabolism in reforming immune cells and microenvironment. Finally, the results of our study endorsed the potential application of SGMRS to guide the selection of immunotherapy for gliomas.