bluuebunny/crossref_metadata_2025 huggingface dataset:
What Are the Barriers and Enablers to the Implementation of Pharmacogenetic Testing in Mental Health Care Settings?
Authors: Jameson Adam , Fylan Beth , Bristow Greg C. , Sagoo Gurdeep S. , Dalton Caroline , Cardno Alastair , Sohal Jaspreet , McLean Samantha L.
Published: September 2021

In psychiatry, the selection of antipsychotics and antidepressants is generally led by a trial-and-error approach. The prescribing of these medications is complicated by sub-optimal efficacy and high rates of adverse drug reactions (ADRs). These both contribute to poor levels of adherence. Pharmacogenetics (PGx) considers how genetic variation can influence an individual’s response to a drug. Pharmacogenetic testing is a tool that could aid clinicians when selecting psychotropic medications, as part of a more personalized approach to prescribing. This may improve the use of and adherence to these medications. Yet to date, the implementation of PGx in mental health environments in the United Kingdom has been slow. This review aims to identify the current barriers and enablers to the implementation of PGx in psychiatry and determine how this can be applied to the uptake of PGx by NHS mental health providers. A systematic searching strategy was developed, and searches were carried out on the PsychInfo, EmBase, and PubMed databases, yielding 11 appropriate papers. Common barriers to the implementation of PGx included cost, concerns over incorporation into current workflow and a lack of knowledge about PGx; whilst frequent enablers included optimism that PGx could lead to precision medicine, reduce ADRs and become a more routine part of psychiatric clinical care. The uptake of PGx in psychiatric care settings in the NHS should consider and overcome these barriers, while looking to capitalize on the enablers identified in this review.
Neonatal LPS Administered Before Sensitization Reduced the Number of Inflammatory Monocytes and Abrogated the Development of OVA-Induced Th2 Allergic Airway Inflammation
Authors: Gao Liuchuang , Wu Min , Liu Hangyu , He Miao , Jiang Han , Shang Runshi , Wang Qiangqiang , Song Zhu , Huang Yafei , Han Junyan
Published: September 2021

It is becoming increasingly clear that environment factors during early life play a pivotal role in the development of allergic asthma. Among these, a traditional farm is one of the strongest protective environments, and the protective effects have been, at least in part, attributed to the high-level exposure to lipopolysaccharide (LPS) on farms. However, the underlying mechanisms remain elusive, especially in ovalbumin (OVA)-induced neonatal allergic asthma model. Here, we used the OVA-induced asthma model in two age groups, neonatal and adult, when mice were first sensitized with peritoneal OVA/alum as neonates and adults, respectively. LPS was injected in the peritoneal cavity before OVA/alum sensitization. The effects of LPS treatment on allergic airway inflammation in the lung and the immune milieu in the peritoneal cavity were determined and compared between these two age groups. We found that LPS treatment abrogated the development of Th2 allergic airway responses in the neonatal group. In the adult group, the ameliorated Th2 allergic responses were accompanied with Th17 responses and neutrophil infiltration upon LPS treatment. We further investigated the immune milieu in the peritoneal cavity to elucidate the underlying mechanisms of this age-dependent difference. Our data show that in neonatal mice, LPS treatment significantly reduced the number of inflammatory monocytes in the peritoneal cavity. In the adult group, LPS treatment shifted the function of these cells which associated with Th1 and Th17 polarization. Our results provide more evidence that immunity in early life is distinct from that in adults, especially in the peritoneal cavity, and emphasize the importance of timing for the intervention of allergic asthma. Our results suggest that LPS treatment during early life is protective for the development of Th2 allergic responses. On the other hand, it might lead to a more severe phenotype of asthma when dampening the Th2 responses in adult mice.
Considering Commercial Vessels as Potential Vectors of Stony Coral Tissue Loss Disease
Authors: Rosenau Nicholas A. , Gignoux-Wolfsohn Sarah , Everett Richard A. , Miller A. Whitman , Minton Mark S. , Ruiz Gregory M.
Published: September 2021

Stony coral tissue loss disease (SCTLD) is a troubling new disease that is spreading rapidly across the greater Caribbean region, but the etiological agent(s) and the mechanisms(s) of spread are both unknown. First detected off the coast of Miami, Florida, major ocean currents alone do not explain the pattern of spread, with outbreaks occurring across geographically disjunct and distant locations. This has raised concerns by researchers and resource managers that commercial vessels may contribute as vectors to spread of the disease. Despite existing regulatory and management strategies intended to limit coastal marine invasion risks, the efficacy of these measures is still unresolved for ship-borne microorganisms, and disease transport via ballast water and hull biofouling are under examination given the high ship traffic in the region. Here, to help inform the discussion of ships as possible vectors of SCTLD, we provide an overview of the current state of knowledge about ships and their potential to transfer organisms in the greater Caribbean, focusing in particular on ballast water, and outline a set of recommendations for future research.
Within- and Trans-Generational Environmental Adaptation to Climate Change: Perspectives and New Challenges
Authors: Bautista Naim M. , Crespel Amélie
Published: September 2021

The current and projected impacts of climate change are shaped by unprecedented rates of change in environmental conditions. These changes likely mismatch the existing coping capacities of organisms within-generations and impose challenges for population resilience across generations. To better understand the impacts of projected scenarios of climate change on organismal fitness and population maintenance, it is crucial to consider and integrate the proximate sources of variability of plastic and adaptive responses to environmental change in future empirical approaches. Here we explore the implications of considering: (a) the variability in different time-scale events of climate change; (b) the variability in plastic responses from embryonic to adult developmental stages; (c) the importance of considering the species life-history traits; and (d) the influence of trans-generational effects for individual survival and population maintenance. Finally, we posit a list of future challenges with questions and approaches that will help to elucidate knowledge gaps, to better inform conservation and management actions in preserving ecosystems and biodiversity.
Chemical Tuning on Resonance Coupling in Gold Nanorod−Monolayer WS2 Heterostructures
Authors: Wen Shiya , Deng Shiyu , Chen Kun , Chen Huanjun , Deng Shaozhi
Published: September 2021

Resonance coupling between plasmonic resonances in metallic nanostructures and excitons in two-dimensional (2D) semiconductors has attracted much recent attention. The 2D semiconductor excitons are sensitive to external stimulus, enabling active tuning on the resonance couplings by physical, such as applying electrostatic gating, thermal scanning, etc., or chemical approaches. Among the others, chemical tuning approach has the advantage of facile implementation, high efficiency, and being capable of large-area tuning. Here, we report on chemical tuning of resonance coupling in heterostructures consisted of individual gold nanorods integrated with monolayer WS2. We showed that by incubating the heterostructures into a bis (trifluoro-methane) sulfonimide (TFSI) solution, the exciton transition strength of the WS2 will be enhanced significantly. As a result, the resonance coupling in the heterostructures evolved from a weak coupling regime to a strong coupling one, with the mode splitting energy increases from 94.96 to 105.32 meV. These findings highlight the potential of chemical treatment as an efficient technique for tailoring the interactions between plasmonic nanostructures and 2D semiconductors.
Application of Proteomics in Cancer: Recent Trends and Approaches for Biomarkers Discovery
Authors: Kwon Yang Woo , Jo Han-Seul , Bae Sungwon , Seo Youngsuk , Song Parkyong , Song Minseok , Yoon Jong Hyuk
Published: September 2021

Proteomics has become an important field in molecular sciences, as it provides valuable information on the identity, expression levels, and modification of proteins. For example, cancer proteomics unraveled key information in mechanistic studies on tumor growth and metastasis, which has contributed to the identification of clinically applicable biomarkers as well as therapeutic targets. Several cancer proteome databases have been established and are being shared worldwide. Importantly, the integration of proteomics studies with other omics is providing extensive data related to molecular mechanisms and target modulators. These data may be analyzed and processed through bioinformatic pipelines to obtain useful information. The purpose of this review is to provide an overview of cancer proteomics and recent advances in proteomic techniques. In particular, we aim to offer insights into current proteomics studies of brain cancer, in which proteomic applications are in a relatively early stage. This review covers applications of proteomics from the discovery of biomarkers to the characterization of molecular mechanisms through advances in technology. Moreover, it addresses global trends in proteomics approaches for translational research. As a core method in translational research, the continued development of this field is expected to provide valuable information at a scale beyond that previously seen.
A Molecular Survey of Bacterial Species in the Guts of Black Soldier Fly Larvae (Hermetia illucens) Reared on Two Urban Organic Waste Streams in Kenya
Authors: Shumo Marwa , Khamis Fathiya M. , Ombura Fidelis Levi , Tanga Chrysantus M. , Fiaboe Komi K. M. , Subramanian Sevgan , Ekesi Sunday , Schlüter Oliver K. , van Huis Arnold , Borgemeister Christian
Published: September 2021

Globally, the expansion of livestock and fisheries production is severely constrained due to the increasing costs and ecological footprint of feed constituents. The utilization of black soldier fly (BSF) as an alternative protein ingredient to fishmeal and soybean in animal feed has been widely documented. The black soldier fly larvae (BSFL) used are known to voraciously feed and grow in contaminated organic wastes. Thus, several concerns about their safety for inclusion into animal feed remain largely unaddressed. This study evaluated both culture-dependent sequence-based and 16S rDNA amplification analysis to isolate and identify bacterial species associated with BSFL fed on chicken manure (CM) and kitchen waste (KW). The bacteria species from the CM and KW were also isolated and investigated. Results from the culture-dependent isolation strategies revealed that Providencia sp. was the most dominant bacterial species detected from the guts of BSFL reared on CM and KW. Morganella sp. and Brevibacterium sp. were detected in CM, while Staphylococcus sp. and Bordetella sp. were specific to KW. However, metagenomic studies showed that Providencia and Bordetella were the dominant genera observed in BSFL gut and processed waste substrates. Pseudomonas and Comamonas were recorded in the raw waste substrates. The diversity of bacterial genera recorded from the fresh rearing substrates was significantly higher compared to the diversity observed in the gut of the BSFL and BSF frass (leftovers of the rearing substrates). These findings demonstrate that the presence and abundance of microbiota in BSFL and their associated waste vary considerably. However, the presence of clinically pathogenic strains of bacteria in the gut of BSFL fed both substrates highlight the biosafety risk of potential vertical transmission that might occur, if appropriate pre-and-postharvest measures are not enforced.
RNA m1A Methyltransferase TRMT6 Predicts Poorer Prognosis and Promotes Malignant Behavior in Glioma
Authors: Wang Beibei , Niu Lihua , Wang Zhengyang , Zhao Zhihua
Published: September 2021

Background: Glioma is the most prevalent central nervous system tumor in humans, and its prognosis remains unsatisfactory due to a lack of effective therapeutic targets. The ectopic expression of N1-methyladenosine (m1A) regulators is a key participant in tumorigenesis and progression. However, the m1A regulator expression status, prognostic value, and relationship with tumor clinical features in glioma remain unclear.

Methods: Public datasets were used to analyze the mRNA and protein expression levels of m1A regulators. Kaplan–Meier and Cox regression analyses were performed to confirm the prognostic value of m1A regulators in glioma. Cellular experiments were conducted to verify the effect of TRMT6 on cell function. A comprehensive bioinformatics analysis was conducted to identify the potential molecular mechanisms regulated by TEMT6 in glioma.

Results: We found that the dysregulation of m1A regulators was closely associated with tumorigenesis and progression in glioma. Furthermore, TRMT6 might be a powerful and independent biomarker for prognosis in glioma. Our study showed that inhibition of TRMT6 suppressed the proliferation, migration, and invasion of glioma cells. Mechanistically, TRMT6 may be involved in glioma progression by regulating cell cycle, PI3K-AKT, TGF-beta, MTORC1, NOTCH, and MYC pathways.

Conclusions: Variation in m1A regulators was closely associated with malignant progression in glioma. Silencing TRMT6 suppressed the cell proliferation, migration, and invasion in glioma. m1A regulators, especially TRMT6, might play an essential role in the malignant progression of glioma.
Sirtuins as Potential Therapeutic Targets for Mitigating Neuroinflammation Associated With Alzheimer’s Disease
Authors: Fernando Kurukulasooriya Kavindya Madushani , Wijayasinghe Yasanandana Supunsiri
Published: September 2021

Alzheimer’s disease (AD) is the most common neurodegenerative disorder, which is associated with memory deficit and global cognitive decline. Age is the greatest risk factor for AD and, in recent years, it is becoming increasingly appreciated that aging-related neuroinflammation plays a key role in the pathogenesis of AD. The presence of β-amyloid plaques and neurofibrillary tangles are the primary pathological hallmarks of AD; defects which can then activate a cascade of molecular inflammatory pathways in glial cells. Microglia, the resident macrophages in the central nervous system (CNS), are the major triggers of inflammation; a response which is typically intended to prevent further damage to the CNS. However, persistent microglial activation (i.e., neuroinflammation) is toxic to both neurons and glia, which then leads to neurodegeneration. Growing evidence supports a central role for sirtuins in the regulation of neuroinflammation. Sirtuins are NAD+-dependent protein deacetylases that modulate a number of cellular processes associated with inflammation. This review examines the latest findings regarding AD-associated neuroinflammation, mainly focusing on the connections among the microglial molecular pathways of inflammation. Furthermore, we highlight the biology of sirtuins, and their role in neuroinflammation. Suppression of microglial activity through modulation of the sirtuin activity has now become a key area of research, where progress in therapeutic interventions may slow the progression of Alzheimer’s disease.
Genotype-Phenotype Correlations in Monogenic Parkinson Disease: A Review on Clinical and Molecular Findings
Authors: Guadagnolo Daniele , Piane Maria , Torrisi Maria Rosaria , Pizzuti Antonio , Petrucci Simona
Published: September 2021

Parkinson disease (PD) is a complex neurodegenerative disorder, usually with multifactorial etiology. It is characterized by prominent movement disorders and non-motor symptoms. Movement disorders commonly include bradykinesia, rigidity, and resting tremor. Non-motor symptoms can include behavior disorders, sleep disturbances, hyposmia, cognitive impairment, and depression. A fraction of PD cases instead is due to Parkinsonian conditions with Mendelian inheritance. The study of the genetic causes of these phenotypes has shed light onto common pathogenetic mechanisms underlying Parkinsonian conditions. Monogenic Parkinsonisms can present autosomal dominant, autosomal recessive, or even X-linked inheritance patterns. Clinical presentations vary from forms indistinguishable from idiopathic PD to severe childhood-onset conditions with other neurological signs. We provided a comprehensive description of each condition, discussing current knowledge on genotype-phenotype correlations. Despite the broad clinical spectrum and the many genes involved, the phenotype appears to be related to the disrupted cell function and inheritance pattern, and several assumptions about genotype-phenotype correlations can be made. The interest in these assumptions is not merely speculative, in the light of novel promising targeted therapies currently under development.
Systematic Monitoring of Cognition for Adults With Cerebral Palsy—The Rationale Behind the Development of the CPCog-Adult Follow-Up Protocol
Authors: Stadskleiv Kristine , van Walsem Marleen R. , Andersen Guro L. , Bergqvist Lena , Bøttcher Louise , Christensen Klaus , Heyerdahl David , Hollung Sandra Julsen , Høye Helene , Jahnsen Reidun , Klevberg Gunvor L. , Lindquist Barbro , Passmark Henrik , Rike Per-Ola , Rodby-Bousquet Elisabet , Alriksson-Schmidt Ann I.
Published: September 2021

Cerebral palsy (CP) comprises a heterogeneous group of conditions recognized by disturbances of movement and posture and is caused by a non-progressive injury to the developing brain. Birth prevalence of CP is about 2–2.5 per 1,000 live births. Although the motor impairment is the hallmark of the diagnosis, individuals with CP often have other impairments, including cognitive ones. Cognitive impairments may affect communication, education, vocational opportunities, participation, and mental health. For many years, CP has been considered a “childhood disability,” but the challenges continue through the life course, and health issues may worsen and new challenges may arise with age. This is particularly true for cognitive impairments, which may become more pronounced as the demands of life increase. For individuals with CP, there is no one-to-one correlation between cognition and functioning in other areas, and therefore, cognition must be individually assessed to determine what targeted interventions might be beneficial. To facilitate this for children with CP, a systematic follow-up protocol of cognition, the CPCog, has been implemented in Norway and Sweden. However, no such protocol currently exists for adults with CP. Such discontinuity in healthcare services that results from lack of follow-up of cognitive functioning and subsequent needs for adjustments and interventions makes transition from pediatric to adult healthcare services challenging. As a result, a protocol for the surveillance of cognition in adults with CP, the CPCog-Adult, has been developed. It includes assessment of verbal skills, non-verbal reasoning, visual–spatial perception, and executive functioning. It is recommended to perform these assessments at least once in young adulthood and once in the mid-fifties. This report describes the process of developing the CPCog-Adult, which has a three-fold purpose: (1) to provide equal access to healthcare services to enable the detection of cognitive impairments; (2) to provide interventions that increase educational and vocational participation, enhance quality of life, and prevent secondary impairments; and (3) to collect systematic data for research purposes. The consent-based registration of data in the well-established Swedish and Norwegian national CP registries will secure longitudinal data from childhood into adulthood.
Effects of Obstructive Sleep Apnea Syndrome and Medical Comorbidities on Language Abilities
Authors: Makanikas Konstantinos , Andreou Georgia , Simos Panagiotis , Chartomatsidou Efstathia
Published: September 2021

Objective: The primary objective of the present cross-sectional study is to evaluate the semantic language abilities of patients with Obstructive Sleep Apnea Syndrome (OSAS) compared to normative data. Secondary objectives are to examine the effects of OSAS comorbidities on language test performance.

Method: 118 adult patients suffering from OSAS were assessed using standardized tests (Boston Naming Test, the Peabody Picture Vocabulary Test and the Verbal Fluency Test).

Results: Compared to normative standards, the OSAS group (age and education adjusted mean) scored significantly lower on all tests (p < 0.01). The OSAS group also included a significantly higher percentage of persons scoring below the 5th percentile of the normative distribution on the four tests (p < 0.01). The Apnea/Hypopnea Index, O2 Desaturation index, SaO2 <85% (min) and SaO2 <75% (min) were significantly associated with language test scores (p < 0.05). Moreover, higher Apnea–Hypopnea Index score and night-time oxygen desaturation were associated with reduced phonemic and semantic fluency performance only among patients with a history of hypertension and hypercholesterolemia (p < 0.05). The moderating effect of diabetes and cardiovascular disease on the association between OSAS severity indices and test scores did not reach significance (p > 0.6).

Conclusions: Results suggest that the severity of semantic language impairments in patients with OSAS is associated with the severity of the disease and intensified by common medical comorbidities (hypertension and hypercholesterolemia).
Task Complexity and Image Clarity Facilitate Motor and Visuo-Motor Activities in Mirror Therapy in Post-stroke Patients
Authors: Bello Umar Muhammad , Chan Chetwyn C. H. , Winser Stanley John
Published: September 2021

Introduction:Mirror therapy is effective in the recovery of upper-limb function among post-stroke patients. An important component of mirror therapy is imagining finger movements. This study aimed to determine the influence of finger movement complexity and mirror image clarity on facilitating motor and visuo-motor activities in post-stroke patients.

Methods:Fifteen post-stroke patients and 18 right-handed healthy participants performed simple or complex finger tapping while viewing mirror images of these movements at varying levels of clarity. The physical setup was identical to typical mirror therapy. Functional near infrared spectroscopy (fNIRS) was used to capture the brain activities elicited in the bilateral primary motor cortices (M1) and the precuneus using a block experimental design.

Results:In both study groups, the “complex finger-tapping task with blurred mirror image” condition resulted in lower intensity (p< 0.01) and authenticity (p< 0.01) of the kinesthetic mirror illusion, and higher levels of perceived effort in generating the illusion (p< 0.01), relative to the “simple finger-tapping with clear mirror image” condition. Greater changes in the oxygenated hemoglobin (HbO) concentration were recorded at the ipsilesional and ipsilateral M1 in the “complex finger-tapping task with blurred mirror image” condition relative to that recorded in the “simple finger-tapping task with clear mirror image” condition (p= 0.03). These HbO concentration changes were not significant in the precuneus. Post-stroke patients showed greater changes than their healthy counterparts at the ipsilesional M1 (F= 5.08;p= 0.03; partial eta squared = 0.14) and the precuneus (F= 7.71;p< 0.01; partial eta squared = 0.20).

Conclusion:The complexity and image clarity of the finger movements increased the neural activities in the ipsilesional motor cortex in the post-stroke patients. These findings suggest plausible roles for top-down attention and working memory in the treatment effects of mirror therapy. Future research can aim to corroborate these findings by using a longitudinal design to examine the use of mirror therapy to promote upper limb motor recovery in post-stroke patients.
Statin Use and Outcomes of Patients With Acute Ischemic Stroke Treated With Intravenous Thrombolysis: A Systematic Review and Meta-Analysis
Authors: Guo Yu , Guo Xinmei , Zhao Kai , Bao Qiangji , Yang Jincai , Yang Mingfei
Published: September 2021

Background: The data on the relationship between statin use and clinical outcomes after intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) are in controversy.

Objective: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of statins administered prior to onset and during hospitalization in patients with AIS treated with IVT.

Methods: We searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials from inception until June 8, 2021. Comparative studies investigating statin effect on intracranial hemorrhage (ICH), functional outcomes, and mortality in adults with AIS treated with IVT were screened. Random-effect meta-analyses of odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were performed. The protocol was registered in PROSPERO (CRD42021254919).

Results: Twenty-two observational studies were included, which involved 17,554 patients. The pooled estimates showed that pre-stroke statin use was associated with a higher likelihood of symptomatic ICH (OR 1.31; 95% CI 1.07–1.59; p = 0.008) and any ICH (OR 1.21; 95% CI 1.03–1.43; p = 0.02). However, the pre-stroke statin use was not significantly associated with the 3-month mortality, 3-month favorable functional outcome (FFO, modified Rankin Scale [mRS] score 0–1), and 3-month functional independence (FI; mRS score 0–2). However, in-hospital statin use was associated with a reduced risk of symptomatic ICH (OR 0.46; 95% CI 0.21–1.00; p = 0.045), any ICH (OR 0.51; 95% CI 0.27–0.98; p = 0.04), and 3-month mortality (OR 0.42; 95% CI 0.29–0.62; p < 0.001) and an increased probability of 3-month FFO (OR 1.33; 95% CI 1.02–1.744; p = 0.04) and 3-month FI (OR 1.41; 95% C, 1.11–1.80; p = 0.005).

Conclusions: The present systematic review and meta-analysis suggests that in-hospital statin use after IVT may be safe and may have a favorable impact on clinical outcomes, a finding not observed in studies restricted to patients with pre-stroke statin use.
Altered Functional Topological Organization in Type-2 Diabetes Mellitus With and Without Microvascular Complications
Authors: Zhang Dongsheng , Huang Yang , Gao Jie , Lei Yumeng , Ai Kai , Tang Min , Yan Xuejiao , Lei Xiaoyan , Yang Zhen , Shao Zhirong , Zhang Xiaoling
Published: September 2021

Microvascular complications can accelerate cognitive impairment in patients with type 2 diabetes mellitus (T2DM) and have a high impact on their quality of life; however, the underlying mechanism is still unclear. The complex network in the human brain is the physiological basis for information processing and cognitive expression. Therefore, this study explored the relationship between the functional network topological properties and cognitive function in T2DM patients with and without microvascular complications (T2DM-C and T2DM-NC, respectively). Sixty-seven T2DM patients and 41 healthy controls (HCs) underwent resting-state functional MRI and neuropsychological assessment. Then, graph theoretical network analysis was performed to explore the global and nodal topological alterations in the functional whole brain networks of T2DM patients. Correlation analyses were performed to investigate the relationship between the altered topological parameters and cognitive/clinical variables. The T2DM-C group exhibited significantly higher local efficiency (Eloc), normalized cluster coefficient (γ), and small-world characteristics (σ) than the HCs. Patients with T2DM at different clinical stages (T2DM-C and T2DM-NC) showed varying degrees of abnormalities in node properties. In addition, compared with T2DM-NC patients, T2DM-C patients showed nodal properties disorders in the occipital visual network, cerebellum and middle temporal gyrus. The Eloc metrics were positively correlated with HbA1c level (P = 0.001, r = 0.515) and the NE values in the right paracentral lobule were negatively related with serum creatinine values (P = 0.001, r = −0.517) in T2DM-C patients. This study found that T2DM-C patients displayed more extensive changes at different network topology scales. The visual network and cerebellar may be the central vulnerable regions of T2DM-C patients.
Micronutrients May Be a Unique Weapon Against the Neurotoxic Triad of Excitotoxicity, Oxidative Stress and Neuroinflammation: A Perspective
Authors: Holton Kathleen F.
Published: September 2021

Excitotoxicity has been implicated in many neurological disorders and is a leading cause of oxidative stress and neuroinflammation in the nervous system. Most of the research to date has focused on each of these conditions individually; however, excitotoxicity, oxidative stress, and neuroinflammation have the ability to influence one another in a self-sustaining manner, thus functioning as a “neurotoxic triad.” This perspective article re-introduces the concept of the neurotoxic triad and reviews how specific dietary micronutrients have been shown to protect against not only oxidative stress, but also excitotoxicity and neuroinflammation. Future dietary interventions for neurological disorders could focus on the effects on all three aspects of the neurotoxic triad.
Effects of Oligomeric Procyanidins From Lotus Seedpod on the Retrogradation Properties of Rice Starch
Authors: Feng Nianjie , She Shaowen , Hu Hengfeng , Tang Shimiao , Tan Jiangying , Wu Qian , Xiao Juan
Published: September 2021

The extent of retrogradation strongly affects certain physical and cooking properties of rice starch (RS), which are important to consumers. In this study, oligomeric procyanidins from lotus seedpod (LSOPC) was prepared and used to investigate its inhibitory effect on RS retrogradation. Various structural changes of RS during retrogradation were characterized by differential scanning calorimetry, low field nuclear magnetic resonance, X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy. The results showed LSOPC could effectively retard both short- and long-term retrogradation of RS, and its inhibitory effect was dependent on the administered concentration of LSOPC. Molecule simulation revealed the interactions of RS and LSOPC, which indicated that the competition of hydrogen bonds between RS and LSOPC was the critical factor for anti-retrogradation. This inhibitory effect and mechanism of action of LSOPC could promote its applications in the field of starch anti-retrogradation.
Case Report: Pathological Complete Response in a Brain-Metastatic Lung Squamous Cell Carcinoma Patient With Long-Term Benefit From Chemo-Immunotherapy
Authors: Hu Chen , Ma Qiang , Li Nengsheng , Luo Nuo , Hao Shuai , Jiang Minrui , Pang Fei , Yang Yan , Li Li , He Yong
Published: September 2021

Immune checkpoint inhibitors have brought long-term survival benefit in advanced non-small cell lung cancer patients without driver gene mutations. Even after withdrawal of immunotherapy for a maximum of two years, some patients still benefit from this therapy and the reason is not fully clear. Results from several neoadjuvant trials indicated that in resectable lung cancer patients, neoadjuvant immunotherapy or chemo-immunotherapy led to major or complete pathological responses in a high proportion of tumors. Here we report a case of a brain-metastatic lung squamous cell carcinoma patient who received supratentorial tumor resection and thoracic surgery after chemo-immunotherapy, and achieved a pathological complete response (pCR) in both lesions. This case indicated that pCR can also happen in advanced-stage lung cancer patients receiving chemo-immunotherapy, which may be the reason for long-term benefit of those patients.
LncRNA SNHG7 Regulates Mesenchymal Stem Cell Through the Notch1/Jagged1/Hes-1 Signaling Pathway and Influences Folfirinox Resistance in Pancreatic Cancer
Authors: Cheng Dongfeng , Fan Juanjuan , Qin Kai , Zhou Yiran , Yang Jingrui , Ma Yang , Shi Minmin , Jin Jiabin
Published: September 2021

Pancreatic cancer (PC) is one of the deadliest gastrointestinal cancers, accounting for the fourth highest number of cancer-related fatalities. Increasing data suggests that mesenchymal stem cells (MSCs) might influence the drug resistance of GC cells in the tumor microenvironment and play essential roles in drug resistance development. However, the precise underlying process remains a mystery. The purpose of this study was to look at the control of MSC-induced SNHG7 in pancreatic cancer. In vitro and in vivo sphere formation, colony formation, and flow cytometry investigations revealed the stemness and Folfirinox resistance in pancreatic cancer cells. To confirm the direct connections between SNHG7 and other related targets, RNA pulldown and immunoprecipitation tests were performed. MSC co-culture enhanced the stemness and Folfirinox resistance in pancreatic cancer cells according to the findings. MSC co-culture increased SNHG7 expression in pancreatic cancer cells, contributing to the stemness and Folfirinox resistance. We demonstrated that Notch1 interacted with SNHG7 and could reverse the facilitative effect of SNHG7 on the stemness and Folfirinox resistance in pancreatic cancer cells. Finally, our findings showed that MSCs increased SNHG7 expression in pancreatic cancer cells, promoting the stemness and Folfirinox resistance via the Notch1/Jagged1/Hes-1 signaling pathway. These findings could provide a novel approach and therapeutic target for pancreatic cancer patients.
Endoscopic Endonasal Surgical Strategy for Skull Base Chordomas Based on Tumor Growth Directions: Surgical Outcomes of 167 Patients During 3 Years
Authors: Bai Jiwei , Li Mingxuan , Xiong Yujia , Shen Yutao , Liu Chunhui , Zhao Peng , Cao Lei , Gui Songbai , Li Chuzhong , Zhang Yazhuo
Published: September 2021

Background

Skull base chordomas (SBCs) are rare malignant bone tumors with dismal long-term local control. Endoscopic endonasal surgeries (EESs) are increasingly adopted to resect SBCs recently. Gross total resection (GTR) favors good outcomes. However, the SBCs often invade the skull base extensively and hide behind vital neurovascular structures; the tumors were challenging to remove entirely. To improve the GTR, we established a surgical strategy for EES according to the tumor growth directions.

Methods

A total of 112 patients with SBCs from 2018 to 2019 were classified into the derivation group. We retrospectively analyzed their radiologic images and operation videos to find the accurate tumor locations. By doing so, we confirmed the tumor growth directions and established a surgical strategy. Fifty-five patients who were operated on in 2020 were regarded as the validation group, and we performed their operations following the surgical strategy to verify its value.

Results

In the derivation group, 78.6% of SBCs invade the dorsum sellae and posterior clinoid process region. 62.5% and 69.6% of tumors extend to the left and right posterior spaces of cavernous ICA, respectively. 59.8% and 61.6% of tumors extend to the left and right posterior spaces of paraclival and lacerum ICA (pc-la ICA), respectively. 30.4% and 28.6% of tumors extended along the left and right petroclival fissures that extend toward the jugular foramen, respectively. 30.4% of tumors involved the foramen magnum and craniocervical junction region. The GTR was achieved in 60.8% of patients with primary SBCs in the derivation group. Based on the tumors’ growth pattern, pituitary transposition and posterior clinoidectomy techniques were adopted to resect tumors that hid behind cavernous ICA. Paraclival ICA transposition was used when the tumor invaded the posterior spaces of pc-la ICA. Lacerum fibrocartilage resection and eustachian tube transposition may be warranted to resect the tumors that extended to the jugular foramen. GTR was achieved in 75.0% of patients with primary SBCs in the validation group.

Conclusion

Besides the midline clival region, the SBCs frequently grow into the eight spaces mentioned above. The surgical strategy based on the growth pattern contributes to increasing the GTR rate.
Non-Mass Enhancements on DCE-MRI: Development and Validation of a Radiomics-Based Signature for Breast Cancer Diagnoses
Authors: Li Yan , Yang Zhenlu L. , Lv Wenzhi Z. , Qin Yanjin J. , Tang Caili L. , Yan Xu , Guo Yihao H. , Xia Liming M. , Ai Tao
Published: September 2021

Purpose

We aimed to assess the additional value of a radiomics-based signature for distinguishing between benign and malignant non-mass enhancement lesions (NMEs) on dynamic contrast-enhanced breast magnetic resonance imaging (breast DCE-MRI).

Methods

In this retrospective study, 232 patients with 247 histopathologically confirmed NMEs (malignant: 191; benign: 56) were enrolled from December 2017 to October 2020 as a primary cohort to develop the discriminative models. Radiomic features were extracted from one post-contrast phase (around 90s after contrast injection) of breast DCE-MRI images. The least absolute shrinkage and selection operator (LASSO) regression model was adapted to select features and construct the radiomics-based signature. Based on clinical and routine MR features, radiomics features, and combined information, three discriminative models were built using multivariable logistic regression analyses. In addition, an independent cohort of 72 patients with 72 NMEs (malignant: 50; benign: 22) was collected from November 2020 to April 2021 for the validation of the three discriminative models. Finally, the combined model was assessed using nomogram and decision curve analyses.

Results

The routine MR model with two selected features of the time-intensity curve (TIC) type and MR-reported axillary lymph node (ALN) status showed a high sensitivity of 0.942 (95%CI, 0.906 - 0.974) and low specificity of 0.589 (95%CI, 0.464 - 0.714). The radiomics model with six selected features was significantly correlated with malignancy (P<0.001 for both primary and validation cohorts). Finally, the individual combined model, which contained factors including TIC types and radiomics signatures, showed good discrimination, with an acceptable sensitivity of 0.869 (95%CI, 0.816 to 0.916), improved specificity of 0.839 (95%CI, 0.750 to 0.929). The nomogram was applied to the validation cohort, reaching good discrimination, with a sensitivity of 0.820 (95%CI, 0.700 to 0.920), specificity of 0.864 (95%CI,0.682 to 1.000). The combined model was clinically helpful, as demonstrated by decision curve analysis.

Conclusions

Our study added radiomics signatures into a conventional clinical model and developed a radiomics nomogram including radiomics signatures and TIC types. This radiomics model could be used to differentiate benign from malignant NMEs in patients with suspicious lesions on breast MRI.
The Novel Chinese Medicine JY5 Formula Alleviates Hepatic Fibrosis by Inhibiting the Notch Signaling Pathway
Authors: Fu Yadong , Xiao Zhun , Tian Xiaoting , Liu Wei , Xu Zhou , Yang Tao , Hu Yonghong , Zhou Xiaoxi , Fang Jing , Gao Siqi , Zhang Dingqi , Mu Yongping , Zhang Hua , Hu Yiyang , Huang Chenggang , Chen Jiamei , Liu Ping
Published: September 2021

Advanced liver fibrosis can lead to cirrhosis, resulting in an accelerated risk of hepatocellular carcinoma and liver failure. Fuzheng Huayu formula (FZHY) is a traditional Chinese medicine formula treated liver fibrosis in China approved by a Chinese State Food and Drug Administration (NO: Z20050546), composed of Salvia Miltiorrhiza bge., Prunus davidiana (Carr.) Franch., cultured Cordyceps sinensis (BerK.) Sacc. Mycelia, Schisandra chinensis (Turcz.) Baill., Pinus massoniana Lamb., and Gynostemma pentaphyllum (Thunb.) Makino. However, the main active substances and mechanism of FZHY are unclear. The aim of this study is to identify a novel anti-fibrotic compound, which consists of the main active ingredients of FZHY, and investigate its mechanism of pharmacological action. The main active ingredients of FZHY were investigated by quantitative analysis of FZHY extracts and FZHY-treated plasma and liver in rats. The anti-fibrotic composition of the main active ingredients was studied through uniform design in vivo, and its mechanism was evaluated in carbon tetrachloride (CCl4)- and bile duct ligation (BDL)-induced liver fibrosis models in rats and mice, and transforming growth factor beta 1-induced LX-2 cell activation model in vitro. A novel Chinese medicine, namely JY5 formula, consisting of salvianolic acid B, schisantherin A, and amygdalin, the main active ingredients of FZHY, significantly alleviated hepatic hydroxyproline content and collagen deposition in CCl4-and BDL-induced fibrotic liver in rats and mice. In addition, JY5 inhibited the activation of hepatic stellate cells (HSCs) by inactivating Notch signaling in vitro and in vivo. In this study, we found a novel JY5 formula, which exerted anti-hepatic fibrotic effects by inhibiting the Notch signaling pathway, consequently suppressing HSCs activation. These results provide an adequate scientific basis for clinical research and application of the JY5 formula, which may be a potential novel therapeutic candidate for liver fibrosis.
An Integrative Pharmacology Based Analysis of Refined Liuweiwuling Against Liver Injury: A Novel Component Combination and Hepaprotective Mechanism
Authors: Gao Yuan , Shi Wei , Yao Hongyu , Ai Yongqiang , Li Ruisheng , Wang Zhilei , Liu Tingting , Dai Wenzhang , Xiao Xiaohe , Zhao Jun , Niu Ming , Bai Zhaofang
Published: September 2021

Liver disease is a major cause of illness and death worldwide. In China, liver diseases, primarily alcoholic and nonalcoholic fatty liver disease, and viral hepatitis, affect approximately 300 million people, resulting in a major impact on the global burden of liver diseases. The use of Liuweiwuling (LWWL), a traditional Chinese medicine formula, approved by the Chinese Food and Drug Administration for decreasing aminotransferase levels induced by different liver diseases. Our previous study indicated a part of the material basis and mechanisms of LWWL in the treatment of hepatic fibrosis. However, knowledge of the materials and molecular mechanisms of LWWL in the treatment of liver diseases remains limited. Using pharmacokinetic and network pharmacology methods, this study demonstrated that the active components of LWWL were involved in the treatment mechanism against liver diseases and exerted anti-apoptosis and anti-inflammatory effects. Furthermore, esculetin, luteolin, schisandrin A and schisandrin B may play an important role by exerting anti-inflammatory and hepatoprotective effects in vitro. Esculeti and luteolin dose-dependently inhibited H2O2-induced cell apoptosis, and luteolin also inhibited the NF-κB signaling pathway in bone marrow-derived macrophages. schisandrin A and B inhibited the release of ROS in acetaminophen (APAP)-induced acute liver injury in vitro. Moreover, LWWL active ingredients protect against APAP-induced acute liver injury in mice. The four active ingredients may inhibit oxidative stress or inflammation to exert hepatoprotective effect. In conclusion, our results showed that the novel component combination of LWWL can protect against APAP-induced acute liver injury by inhibiting cell apoptosis and exerting anti-inflammatory effects.
Fluids Alter Elasticity Measurements: Porous Wave Propagation Accounts for Shear Wave Dispersion in Elastography
Authors: Aichele Johannes , Catheline Stefan
Published: September 2021

In shear wave elastography, rotational wave speeds are converted to elasticity measures using elastodynamic theory. The method has a wide range of applications and is the gold standard for non-invasive liver fibrosis detection. However, the observed shear wave dispersion of in vivo human liver shows a mismatch with purely elastic and visco-elastic wave propagation theory. In a laboratory phantom experiment we demonstrate that porosity and fluid viscosity need to be considered to properly convert shear wave speeds to elasticity in soft porous materials. We extend this conclusion to the clinical application of liver stiffness characterization by revisiting in vivo studies of liver elastography. To that end we compare Biot’s theory of poro-visco-elastic wave propagation to Voigt’s visco-elastic model. Our results suggest that accounting for dispersion due to fluid viscosity could improve shear wave imaging in the liver and other highly vascularized organs.
Adhesion Percolation Determines Global Deformation Behavior in Biomimetic Emulsions
Authors: Montel Lorraine , Golovkova Iaroslava , Grigolon Silvia , Wandersman Elie , Prevost Alexis M. , Bertrand Thibault , Pontani Lea-Laetitia
Published: September 2021

Characterizing the mechanical properties of tissues is key for the understanding of fundamental biological processes such as morphogenesis or tumor progression. In particular, the intercellular adhesion forces, mediated by transmembrane proteins like cadherins, are expected to control the topology and viscoelastic behavior of tissues under mechanical stress. In order to understand the influence of adhesion in tissues, we use biomimetic emulsions in which droplets mimic cells and adhere to each other through specific bonds. Here, we tune both the binding energy of the adhesive inter-droplets contacts as well as the fraction of contacts that are adhesive, thereby defining a so-called adhesiveness. Our experimental results show that adhesion prevents the emergence of local order in emulsions even at high packing fractions by preventing energetically costly droplet rearrangements. By studying the deformation of droplets within packings with different average adhesiveness values, we reveal the existence of a threshold value of adhesiveness above which all droplets in a packing are deformed as adhesive ones irrespective of their local adhesive properties. We show that this critical adhesiveness coincides with the threshold for percolation of adhesive structures throughout the tissue. From a biological point of view, this indicates that only a fraction of adhesive cells would be sufficient to tune the global mechanical properties of a tissue, which would be critical during processes such as morphogenesis.