bluuebunny/crossref_metadata_2025 huggingface dataset:
A multi-color video-ophthalmoscopes allows to measure the spectral distribution of light absorption of blood in the human retina
Authors: Tornow Ralf-Peter , Odstrcilik Jan , Kolar Radim
Published: March 2023

Based on our previously developed mono-color video-ophthalmoscope a multi-color video-ophthalmoscope was developed. Using narrow band transmission filters, this instrument allows to measure the pulsatile cardiac cycle induced blood volume changes in the human retina for any wavelength in the sensitivity range of the used CMOS-camera. In this key experiment, video sequences (8 s, 25 fps, 200 frames) of the optic nerve head (ONH) were acquire for seven wavelengths between 475 nm and 677 nm one after the other. After image registration of all frames of each video sequence (to compensate for eye movements) and trend correction (to compensate for slow intensity changes), the amplitude of the cardiac cycle induced light intensity changes (pulsatile absorption amplitude PAA) can be calculated for all seven wavelengths. The results confirmed that the spectral distribution of PAA (λ) follows the distribution of the light absorption of blood. The measured values correspond to the absorption of a thin blood layer of about 0.5 μm thickness.
Optimising the ECMO treatment regimen increases the survival rate for adult patients with acute fulminant myocarditis: A single-centre retrospective cohort study
Authors: Hou Liusheng , Liang Hongkai , Zeng Shiyong , Li Jianwei , Chen Zhou , Liao Xiaozu , Liu Shaozhong , Li Mingxing , Li Binfei , Yuan Yong
Published: March 2023

Background

Applying Extracorporeal membrane oxygenation (ECMO) to patients with acute fulminant myocarditis (AFM) reduces their mortality. The survival rate is 55.6-71.9% for adult AFM patients, which is lower than that for paediatric patients (63-81%). In our centre, the survival rate of ECMO for adult patients with AFM was 66.7% from January 2003 to 2012. In January 2013, the therapeutic regimen was optimised, and then the survival rate increased to 89.1% by January 2022. This article analyses the reasons for the improved survival rate following the optimisation of treatment protocols.

Methods

The data for adult patients with AFM who underwent ECMO for a poor response conventional treatment from January 2003 to January 2022 were reviewed. According to different treatment regimens, the AFM patients were divided into an old and a new regimen group. Univariate and multivariate logistic regression analyses were performed on the data before and after ECMO.

Results

Fifty-five patients were enrolled in the age (31.2 ± 11.3), including 24 males. Forty-nine patients were weaned successfully from ECMO [duration: (4.1 ± 1.8) d], all of whom were discharged from the hospital, with a survival rate of 89.1%. Compared with the old regimen group, the new regimen group had a shorter duration of shock to ECMO, a lower proportion of patients receiving extracorporeal cardiopulmonary resuscitation (ECPR), a lower Vasoactive Inotropic Score (VIS), and lower levels of lactic acid, and high-sensitivity troponin T before ECMO (p < 0.05). Compared with the old regimen group, after ECMO, the new regimen group had lower ECMO flow, lower proportion of left ventricular dilation and lower limb ischemia injury, the duration of ECMO was shorter, and significantly improved the survival rate, the difference was statistically significant (P < 0.05). The duration of shock to ECMO and VIS before ECMO were independent risk factors for the survival rate (p < 0.05).

Conclusion

Early ECMO initiation in adult AFM patients with a poor response to conventional therapy and low-flow ECMO to meet metabolic needs can reduce serious complications affecting the prognosis, may be associated with better outcomes.
The reciprocal changes in dominant species with complete metabolic functions explain the decoupling phenomenon of microbial taxonomic and functional composition in a grassland
Authors: Liu Huaiqiang , Li Frank Yonghong , Liu Jiayue , Shi Chunjun , Tang Kuanyan , Yang Qianhui , Liu Yu , Fu Qiang , Gao Xiaotian , Wang Ning , Guo Wei
Published: March 2023

The decoupling of microbial functional and taxonomic components refers to the phenomenon that a drastic change in microbial taxonomic composition leads to no or only a gentle change in functional composition. Although many studies have identified this phenomenon, the mechanisms underlying it are still unclear. Here we demonstrate, using metagenomics data from a steppe grassland soil under different grazing and phosphorus addition treatments, that there is no “decoupling” in the variation of taxonomic and metabolic functional composition of the microbial community within functional groups at species level. In contrast, the high consistency and complementarity between the abundance and functional gene diversity of two dominant species made metabolic functions unaffected by grazing and phosphorus addition. This complementarity between the two dominant species shapes a bistability pattern that differs from functional redundancy in that only two species cannot form observable redundancy in a large microbial community. In other words, the “monopoly” of metabolic functions by the two most abundant species leads to the disappearance of functional redundancy. Our findings imply that for soil microbial communities, the impact of species identity on metabolic functions is much greater than that of species diversity, and it is more important to monitor the dynamics of key dominant microorganisms for accurately predicting the changes in the metabolic functions of the ecosystems.
Purine metabolism regulates Vibrio splendidus persistence associated with protein aggresome formation and intracellular tetracycline efflux
Authors: Li Yanan , Wood Thomas K. , Zhang Weiwei , Li Chenghua
Published: March 2023

A small subpopulation of Vibrio splendidus AJ01 that was exposed to tetracycline at 10 times the minimal inhibitory concentration (MIC) still survived, named tetracycline-induced persister cells in our previous work. However, the formation mechanisms of persister is largely unknown. Here, we investigated tetracycline-induced AJ01 persister cells by transcriptome analysis and found that the purine metabolism pathway was significantly downregulated, which was consistent with lower levels of ATP, purine, and purine derivatives in our metabolome analysis. Inhibition of the purine metabolism pathway by 6-mercaptopurine (6-MP, inhibits ATP production), increased persister cell formation and accompanied with the decreasing intracellular ATP levels and increasing cells with protein aggresome. On the other hand, the persister cells had reduced intracellular tetracycline concentrations and higher membrane potential after 6-MP treatment. Inhibition of the membrane potential by carbonyl cyanide m-chlorophenyl hydrazone reversed 6-MP-induced persistence and resulted in higher levels of intracellular tetracycline accumulation. Meanwhile, cells with 6-MP treatment increased the membrane potential by dissipating the transmembrane proton pH gradient, which activated efflux to decrease the intracellular tetracycline concentration. Together, our findings show that reduction of purine metabolism regulates AJ01 persistence and is associated with protein aggresome formation and intracellular tetracycline efflux.
Impact of microbial processes on the safety of deep geological repositories for radioactive waste
Authors: Ruiz-Fresneda Miguel A. , Martinez-Moreno Marcos F. , Povedano-Priego Cristina , Morales-Hidalgo Mar , Jroundi Fadwa , Merroun Mohamed L.
Published: March 2023

To date, the increasing production of radioactive waste due to the extensive use of nuclear power is becoming a global environmental concern for society. For this reason, many countries have been considering the use of deep geological repositories (DGRs) for the safe disposal of this waste in the near future. Several DGR designs have been chemically, physically, and geologically well characterized. However, less is known about the influence of microbial processes for the safety of these disposal systems. The existence of microorganisms in many materials selected for their use as barriers for DGRs, including clay, cementitious materials, or crystalline rocks (e.g., granites), has previously been reported. The role that microbial processes could play in the metal corrosion of canisters containing radioactive waste, the transformation of clay minerals, gas production, and the mobility of the radionuclides characteristic of such residues is well known. Among the radionuclides present in radioactive waste, selenium (Se), uranium (U), and curium (Cm) are of great interest. Se and Cm are common components of the spent nuclear fuel residues, mainly as 79Se isotope (half-life 3.27 × 105 years), 247Cm (half-life: 1.6 × 107 years) and 248Cm (half-life: 3.5 × 106 years) isotopes, respectively. This review presents an up-to-date overview about how microbes occurring in the surroundings of a DGR may influence their safety, with a particular focus on the radionuclide-microbial interactions. Consequently, this paper will provide an exhaustive understanding about the influence of microorganisms in the safety of planned radioactive waste repositories, which in turn might improve their implementation and efficiency.
Diseased-induced multifaceted variations in community assembly and functions of plant-associated microbiomes
Authors: Kuang Lu , Li Ting , Wang Baozhan , Peng Junwei , Li Jiangang , Li Pengfa , Jiang Jiandong
Published: March 2023

Plant-associated microorganisms are believed to be part of the so-called extended plant phenotypes, affecting plant growth and health. Understanding how plant-associated microorganisms respond to pathogen invasion is crucial to controlling plant diseases through microbiome manipulation. In this study, healthy and diseased (bacterial wilt disease, BWD) tomato (Solanum lycopersicum L.) plants were harvested, and variations in the rhizosphere and root endosphere microbial communities were subsequently investigated using amplicon and shotgun metagenome sequencing. BWD led to a significant increase in rhizosphere bacterial diversity in the rhizosphere but reduced bacterial diversity in the root endosphere. The ecological null model indicated that BWD enhanced the bacterial deterministic processes in both the rhizosphere and root endosphere. Network analysis showed that microbial co-occurrence complexity was increased in BWD-infected plants. Moreover, higher universal ecological dynamics of microbial communities were observed in the diseased rhizosphere. Metagenomic analysis revealed the enrichment of more functional gene pathways in the infected rhizosphere. More importantly, when tomato plants were infected with BWD, some plant-harmful pathways such as quorum sensing were significantly enriched, while some plant-beneficial pathways such as streptomycin biosynthesis were depleted. These findings broaden the understanding of plant–microbiome interactions and provide new clues to the underlying mechanism behind the interaction between the plant microbiome and BWD.
Increasing lysergic acid levels for ergot alkaloid biosynthesis: Directing catalysis via the F-G loop of Clavine oxidases
Authors: Lim Li Rong , Wong Garrett , Go Maybelle K. , Yew Wen Shan
Published: March 2023

Most ergot alkaloid drugs are semi-synthetically derived from the natural product lysergic acid, a valuable precursor for the development of novel ergot alkaloid drugs. Clavine oxidase (CloA) is a putative cytochrome P450, identified in the ergot alkaloid biosynthesis pathway, and a key enzyme that catalyzes the formation of lysergic acid from the precursor alkaloid agroclavine in a two-step oxidation reaction. We demonstrated in this study that Saccharomyces cerevisiae can be used as a viable host for the functional expression of CloA from Claviceps purpurea and its orthologs. We also showed that CloA orthologs differ in their ability to oxidize the substrate agroclavine, with some orthologs only able to perform the first oxidation reaction to produce elymoclavine. Of particular note, we identified a region between the F-G helices of the enzyme that may be involved in directing oxidation of agroclavine by substrate recognition and uptake. Using this knowledge, engineered CloAs were shown to produce lysergic acid at levels exceeding that of wildtype CloA orthologs; a CloA variant, chimeric AT5 9Hypo CloA, increased production levels of lysergic acid to 15 times higher as compared to the wildtype enzyme, demonstrating future utility for the industrial production of ergot alkaloids using biosynthetic routes.
Integrating the potential of ion mobility spectrometry-mass spectrometry in the separation and structural characterisation of lipid isomers
Authors: Camunas-Alberca Sandra M. , Moran-Garrido Maria , Sáiz Jorge , Gil-de-la-Fuente Alberto , Barbas Coral , Gradillas Ana
Published: March 2023

It is increasingly evident that a more detailed molecular structure analysis of isomeric lipids is critical to better understand their roles in biological processes. The occurrence of isomeric interference complicates conventional tandem mass spectrometry (MS/MS)-based determination, necessitating the development of more specialised methodologies to separate lipid isomers. The present review examines and discusses recent lipidomic studies based on ion mobility spectrometry combined with mass spectrometry (IMS-MS). Selected examples of the separation and elucidation of structural and stereoisomers of lipids are described based on their ion mobility behaviour. These include fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and sterol lipids. Recent approaches for specific applications to improve isomeric lipid structural information using direct infusion, coupling imaging, or liquid chromatographic separation workflows prior to IMS-MS are also discussed, including: 1) strategies to improve ion mobility shifts; 2) advanced tandem MS methods based on activation of lipid ions with electrons or photons, or gas-phase ion-molecule reactions; and 3) the use of chemical derivatisation techniques for lipid characterisation.
The power of a touch: Regular touchscreen training but not its termination affects hormones and behavior in mice
Authors: Quante Sophia Marie , Siewert Viktoria , Palme Rupert , Kaiser Sylvia , Sachser Norbert , Richter S. Helene
Published: March 2023

Touchscreen-based procedures are increasingly used in experimental animal research. They not only represent a promising approach for translational research, but have also been highlighted as a powerful tool to reduce potential experimenter effects in animal studies. However, to prepare the animals for a touchscreen-based test, an often time-consuming training phase is required that has itself been shown to cause increased adrenocortical activity and anxiety-like behavior in mice. While these findings point at a potentially negative effect of touchscreen training at first glance, results have also been discussed in light of an enriching effect of touchscreen training. The aim of the present study was therefore to shed more light on recently reported touchscreen training effects, with a particular focus on the termination of the training routine. Specifically, we investigated whether the termination of regular touchscreen training could constitute a loss of enrichment for mice. Thus, we assessed fecal corticosterone metabolites (FCMs), exploratory-, anxiety-like and home cage behavior in touchscreen-trained mice in comparison to food restricted and ad libitum fed mice, as a restricted diet is an integral part of the training process. Furthermore, we compared these parameters between mice that were continuously trained and mice whose training was terminated 2 weeks earlier. Our results confirm previous findings showing that a mild food restriction increases the animals' exploratory behavior and shifts their activity rhythm. Moreover, touchscreen training was found to increase FCM levels and anxiety-like behavior of the mice. However, no effect of the termination of touchscreen training could be detected, a finding which contradicts the enrichment loss hypothesis. Therefore, we discuss two alternative explanations for the findings. Yet, the current state of knowledge is not sufficient to draw final conclusions at this stage. In compliance with the refinement endeavors for laboratory animals, further research should assess the severity of touchscreen procedures to ensure a responsible and well-founded use of animals for experimental purposes.
Associations of macular microvascular parameters with cerebral small vessel disease in rural older adults: A population-based OCT angiography study
Authors: Xu Zhe , Dong Yi , Wang Yongxiang , Song Lin , Niu Sijie , Wang Shanshan , Zhao Mingqing , Wang Jiafeng , Cong Lin , Han Xiaojuan , Hou Tingting , Tang Shi , Zhang Qinghua , Du Yifeng , Qiu Chengxuan
Published: March 2023

Objective

To explore the associations of macular microvascular parameters with cerebral small vessel disease (CSVD) in rural-dwelling older adults in China.

Methods

This population-based cross-sectional study included 195 participants (age ≥ 60 years; 57.4% women) in the optical coherence tomographic angiography (OCTA) sub-study within the Multimodal Interventions to delay Dementia and disability in rural China (MIND-China). Macular microvascular parameters were measured using the OCTA. We automatically estimated volumes of gray matter, white matter, and white matter hyperintensity (WMH), and manually assessed numbers of enlarged perivascular spaces (EPVS) and lacunes on brain magnetic resonance imaging. Data were analyzed with the general linear models.

Results

Adjusting for multiple confounders, lower vessel skeleton density (VSD) and higher vessel diameter index (VDI) were significantly associated with larger WMH volume (P < 0.05). Lower VSD and foveal density-300 (FD-300) of left eye were significantly associated with lower brain parenchymal volume (P < 0.05). In addition, lower areas of foveal avascular zone (FAZ) and FD-300 of left eye were significantly associated with more EPVS (P < 0.05). The associations of abnormal macular microvascular parameters with WMH volume were evident mainly among females. Macular microvascular parameters were not associated with lacunes.

Conclusion

Macular microvascular signs are associated with WMH, brain parenchymal volume, and EPVS in older adults. The OCTA-assessed macular microvascular parameters can be valuable markers for microvascular lesions in the brain.
Associations between resting state brain activity and A1 adenosine receptor availability in the healthy brain: Effects of acute sleep deprivation
Authors: Li Changhong , Kroll Tina , Matusch Andreas , Aeschbach Daniel , Bauer Andreas , Elmenhorst Eva-Maria , Elmenhorst David
Published: March 2023

Introduction

Previous resting-state fMRI (Rs-fMRI) and positron emission tomography (PET) studies have shown that sleep deprivation (SD) affects both spontaneous brain activity and A1 adenosine receptor (A1AR) availability. Nevertheless, the hypothesis that the neuromodulatory adenosinergic system acts as regulator of the individual neuronal activity remains unexplored.

Methods

Therefore, fourteen young men underwent Rs-fMRI, A1AR PET scans, and neuropsychological tests after 52 h of SD and after 14 h of recovery sleep.

Results

Our findings suggested higher oscillations or regional homogeneity in multiple temporal and visual cortices, whereas decreased oscillations in cerebellum after sleep loss. At the same time, we found that connectivity strengths increased in sensorimotor areas and decreased in subcortical areas and cerebellum.

Discussion

Moreover, negative correlations between A1AR availability and rs-fMRI metrics of BOLD activity in the left superior/middle temporal gyrus and left postcentral gyrus of the human brain provide new insights into the molecular basis of neuronal responses induced by high homeostatic sleep pressure.
Methylation of BDNF gene in association with episodic memory in women
Authors: Alece Arantes Moreno Ivana , Rodrigues de Oliveira Daniela , Ribeiro Borçoi Aline , Fungaro Rissatti Luciana , Vitorino Freitas Flávia , Arantes Lidia Maria Rebolho Batista , Oliveira Mendes Suzanny , dos Santos Vieira Tamires , Risse Quaioto Bárbara , Cerbino Doblas Paola , Sgrancio Olinda Amanda , Ribeiro Cunha Ester , Gasparini dos Santos Joaquim , Assis Pinheiro Júlia , Pereira Sorroche Bruna , Madeira Alvares da Silva Adriana
Published: March 2023

Brain-derived neurotrophic factor (BDNF) gene regulation plays an important role in long-term memory formation, and the DNA methylation (DNAm) level of BDNF promoters has been associated with episodic memory deficits. Our aim was to explore the association between DNAm levels in BDNF promoter IV with verbal learning and memory performance in healthy women. We conducted a cross-sectional study by recruiting 53 individuals. Episodic memory was assessed by using the Rey Auditory Verbal Learning Test (RAVLT). Clinical interviews, RAVLT, and blood sample collection were assessed in all participants. DNAm was measured on DNA from whole peripheral blood using pyrosequencing. According to generalized linear model (GzLM) analyses, cytosine guanine dinucleotide (CpG) site 5 showed significant associations between learning capacity (LC, p < 0.035), that is, every 1% of DNA methylation at CpG site 5 results in a 0.068 reduction in verbal learning performance. To the best of our knowledge, the current study is the first to show that BDNF DNAm plays an important role in episodic memory.
Losing control without your smartphone: Anxiety affects the dynamic choice process of impulsive decision-making and purchase
Authors: Gui Dan-Yang , Dai Yu , Zheng Zhichao , Liu Shixiong
Published: March 2023

Different interacting contexts influence the decision-making process, as revealed by the computational modeling. Through four studies, we investigated how smartphone addiction and anxiety influenced impulsive behaviors, along with the underlying psychological mechanisms and dynamic decision-making processes. In the first and second studies, we found no significant correlation between smartphone addiction and impulsive behavior. However, in the third study, we found that smartphone separation increased impulsive decision-making and purchases, and state anxiety, but not trait anxiety, mediated this effect. We explored the dynamic decision-making process using a multi-attribute drift diffusion model (DDM). The results showed that anxiety triggered by smartphone separation changed the trade-offs between decision weights for the fundamental components of the dynamic choice process. In the fourth study, we investigated why smartphone addiction led to increased anxiety and found that extended-self was a mediating factor. Our findings show that smartphone addiction was not correlated with impulsive behaviors, but was correlated with state anxiety in the context of smartphone separation. Further, this study shows how emotional states triggered by different interacting contexts affect the dynamic decision-making process and consumer behaviors.
Mechanism of ERK/CREB pathway in pain and analgesia
Authors: Zhen Weizhe , Zhen Hongjun , Wang Yuye , Chen Leian , Niu Xiaoqian , Zhang Bin , Yang Ziyuan , Peng Dantao
Published: March 2023

Research has long centered on the pathophysiology of pain. The Transient Receiver Potential (TRP) protein family is well known for its function in the pathophysiology of pain, and extensive study has been done in this area. One of the significant mechanisms of pain etiology and analgesia that lacks a systematic synthesis and review is the ERK/CREB (Extracellular Signal-Regulated Kinase/CAMP Response Element Binding Protein) pathway. The ERK/CREB pathway-targeting analgesics may also cause a variety of adverse effects that call for specialized medical care. In this review, we systematically compiled the mechanism of the ERK/CREB pathway in the process of pain and analgesia, as well as the potential adverse effects on the nervous system brought on by the inhibition of the ERK/CREB pathway in analgesic drugs, and we suggested the corresponding solutions.
Household food insecurity and hunger status in Debre Berhan town, Central Ethiopia: Community-based cross-sectional study
Authors: Demie Takele Gezahegn , Gessese Getachew Tilahun
Published: March 2023

Background

Food security occurs when all people have physical, social, and economic access to sufficient, safe, and nutritious food that fits their dietary needs and food preferences for an active and healthy life at all times. There is limited evidence on this topic and not well studied in Ethiopia.

Objective

This study aimed to investigate food insecurity and hunger status among households (HHs) in Debre Berhan town, Ethiopia.

Methods

A community-based cross-sectional study was undertaken from 1 January 2017 to 30 January 2017. A simple random sampling technique was used to enroll 395 HHs for the study. An interviewer-administered, structured, and pretested questionnaire was used to collect data through a face-to-face interview. The household food security and hunger status were assessed by using the Household Food Insecurity Access Scale and the Household Hunger Scale, respectively. Data were entered and cleaned using Epiata 3.1 and exported to SPSS software version 20 for statistical analysis. Logistic regression was fitted, and an odds ratio with a 95% confidence interval (CI) and a value of p of less than 0.05 were used to identify factors associated with food insecurity.

Results

A total of 377 HHs participated in the study with a response rate of 95.4%. The proportion of households with food insecurity was 32.4%, among which mild, moderate, and severe food insecurity accounted for 10.3, 18.8, and 3.2%, respectively. The mean score of the Household Food Insecurity Access Scale was 1.88 ± 3.5. Hunger occurred among 3.2% of households. The mean score of the Household Hunger Scale was 2.17 ± 1.03. Husband or male cohabitant’s occupation (AOR = 2.68; 95% CI: 1.31–5.48) and wife or female cohabitant’s literacy (AOR = 3.10; 95% CI: 1.01– 9.55) were the only factors associated with HH food insecurity.

Conclusion

HH food insecurity and hunger in Debre Berhan town were unacceptably high, which can hamper achieving national targets for food security, nutrition, and health. Intensified efforts are further needed to accelerate the decline in food insecurity and hunger prevalence. Therefore, interventions need to target self-employed merchants in small businesses and women who are uneducated.
The postbiotic of hawthorn-probiotic ameliorating constipation caused by loperamide in elderly mice by regulating intestinal microecology
Authors: Wei Yu , Huang Na , Ye Xinyu , Liu Meng , Wei Meilian , Huang Yali
Published: March 2023

Background

Constipation is common gastrointestinal disorder with high prevalence and recurrence, making people suffering. However, the treatment for constipation remains ineffectual. We aimed to the study the effects and mechanisms of postbiotic of hawthorn-probiotic on loperamide modeled old KM mice.

Methods

Constipated mice were grouped and treated with 10% lactulose (Y), hawthorn group (S), probiotic group (F) and postbiotic of hawthorn-probiotic (FS). Fecal changes were observed. AQP3 and Enac-γ were measured by RT-qPCR and Western blotting, intestinal barrier by H&E and immunofluorescence staining, cell proliferation and apoptosis by CCK8 and flow cytometry. Gut microbiota was further determined by 16 s rRNA sequence of feces.

Results

Postbiotic of hawthorn-probiotic improved intestinal movement and pathomorphology, elevated AQP3, Enac-γ and mucin-2 expression, accompanied by decreased serum TNF-α and cell apoptosis, but increased proliferation. Furthermore, it modified the gut microbiota of constipated mice, featured by upregulation of Lactobacillaceae.

Conclusion

Postbiotic of hawthorn-probiotic relieved constipation by combined effects of regulating intestinal water and sodium metabolism, maintain intestinal barrier and gut microflora.

Graphical Abstract
Partial replacement of high-fat diet with n-3 PUFAs enhanced beef tallow attenuates dyslipidemia and endoplasmic reticulum stress in tunicamycin-injected rats
Authors: Zheng Jiaxiang , Lee Jisu , Byun Jaemin , Yu Daeung , Ha Jung-Heun
Published: March 2023

Introduction

Metabolic syndrome (MetS) is considered as a complex, intertwined multiple risk factors that directly increase the risk of various metabolic diseases, especially cardiovascular atherosclerotic diseases and diabetes mellitus type 2. While lifestyle changes, including dietary intervention are effective in mitigating or preventing MetS, there are no specific therapies against MetS. Typical western diets comprise of high saturated fatty acid, cholesterol, and simple sugar; consequently their consumption may increase the potential pathological developmental risk of MetS. Partial replacement of dietary fatty acids with polyunsaturated fatty acids (PUFAs) is widely recommended measure to manage MetS-related disorders.

Methods

In the present study, we used rat model to investigate the role of n-3 PUFA enriched beef tallows (BT) on MetS and tunicamycin (TM)-induced endoplasmic reticulum (ER) stress, by partially replacing dietary fat (lard) with equal amounts of two different BTs; regular BT or n-3 PUFA-enriched BT. The experimental rats were randomly assigned to three different dietary groups (n = 16 per group): (1) high-fat and high-cholesterol diet (HFCD); (2) HFCD partially replaced with regular BT (HFCD + BT1); (3) HFCD partially replaced with n-3 enhanced BT (w/w) (HFCD + BT2). After 10 weeks of dietary intervention, each experimental rodent was intraperitoneally injected with either phosphate-buffered saline or 1 mg/kg body weight of TM.

Results

HFCD + BT2 showed improved dyslipidemia before TM injection, and increased serum high-density lipoprotein cholesterol (HDL-C) levels after TM injection. BT replacement groups had significantly reduced hepatic triglyceride (TG) levels, and decreased total cholesterol (TC) and TG levels in epididymal adipose tissue (EAT). Furthermore, BT replacement remarkably attenuated TM-induced unfolded protein responses (UPRs) in liver, showing reduced ER stress, with BT2 being more effective in the EAT.

Discussion

Therefore, our findings suggest that partially replacing dietary fats with n-3 PUFA to lower the ratio of n-6/n-3 PUFAs is beneficial in preventing pathological features of MetS by alleviating HFCD- and/or TM-induced dyslipidemia and ER stress.
Acquired ALK G1202R-, ALK I1171N-, or EML4-ALK-mediated resistance to ensartinib in lung adenocarcinoma but responded to lorlatinib: A case report
Authors: Ye Zhifeng , Guo Junhua
Published: March 2023

ALK rearrangements are identified as driver mutations in non-small-cell lung cancer (NSCLC). EML4 is the most common partner of ALK rearrangements. Here, we reported a patient with lung adenocarcinoma who was identified with EML4-ALK mutations when he progressed on an immune checkpoint inhibitor. The patient was treated with alectinib and obtained a progression-free survival (PFS) of 24 months. Then, next-generation sequencing on circulating tumor DNA identified multiple ALK mutations, including ALK G1202R, I1171N, ALK-ENC1, and EML4-ALK. Ensartinib was given, and the patient achieved a PFS of 5 months. After progression, lorlatinib was administered, and the patient achieved a partial response. Now, the benefit is still ongoing with a PFS over 10 months. Our case may provide evidence for the treatment choice of multiple ALK mutations, including ALK I1171N.
An overall survival predictive nomogram to identify high-risk patients among locoregionally advanced nasopharyngeal carcinoma: Developed based on the SEER database and validated institutionally
Authors: Lin Yinbing , Chen Jiechen , Wang Xiao , Chen Sijie , Yang Yizhou , Hong Yingji , Lin Zhixiong , Yang Zhining
Published: March 2023

Objective

Locoregionally advanced nasopharyngeal carcinoma (LA-NPC) patients, even at the same stage, have different prognoses. We aim to construct a prognostic nomogram for predicting the overall survival (OS) to identify the high-risk LA-NPC patients.

Materials and methods

Histologically diagnosed WHO type II and type III LA-NPC patients in the Surveillance, Epidemiology, and End Results (SEER) database were enrolled as the training cohort (n= 421), and LA-NPC patients from Shantou University Medical College Cancer Hospital (SUMCCH) served as the external validation cohort (n= 763). Variables were determined in the training cohort through Cox regression to form a prognostic OS nomogram, which was verified in the validation cohort, and compared with traditional clinical staging using the concordance index (C-index), Kaplan–Meier curves, calibration curves and decision curve analysis (DCA). Patients with scores higher than the specific cut-off value determined by the nomogram were defined as high-risk patients. Subgroup analyses and high-risk group determinants were explored.

Results

Our nomogram had a higher C-index than the traditional clinical staging method (0.67 vs. 0.60, p<0.001). Good agreement between the nomogram-predicted and actual survival were shown in the calibration curves and DCA, indicating a clinical benefit of the nomogram. High-risk patients identified by our nomogram had worse prognosis than the other groups, with a 5-year overall survival (OS) of 60.4%. Elderly patients at advanced stage and without chemotherapy had a tendency for high risk than the other patients.

Conclusions

Our OS predictive nomogram for LA-NPC patients is reliable to identify high-risk patients.
Could S-1-based non-platinum doublet chemotherapy be a new option as a second-line treatment for advanced non-small cell lung cancer patients? A multicenter retrospective study
Authors: Wang Xiangling , Wang Ting , Chu Yunxia , Liu Jie , Yi Cuihua , Yu Xuejun , Wang Yonggang , Zheng Tianying , Cao Fangli , Qu Linli , Yu Bo , Liu Huayong , Ding Fei , Wang Shuang , Wang Xiangbo , Hao Jing , Wang Xiuwen
Published: March 2023

Background

For patients who have contraindications to or have failed checkpoint inhibitors, chemotherapy remains the standard second-line option to treat non-oncogene-addicted advanced non-small cell lung cancer (NSCLC). This study aimed to investigate the efficacy and safety of S-1-based non-platinum combination in advanced NSCLC patients who had failed platinum doublet chemotherapy.

Methods

During January 2015 and May 2020, advanced NSCLC patients who received S-1 plus docetaxel or gemcitabine after the failure of platinum-based chemotherapy were consecutively retrieved from eight cancer centers. The primary endpoint was progression-free survival (PFS). The secondary endpoint was overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. By using the method of matching-adjusted indirect comparison, the individual PFS and OS of included patients were adjusted by weight matching and then compared with those of the docetaxel arm in a balanced trial population (East Asia S-1 Trial in Lung Cancer).

Results

A total of 87 patients met the inclusion criteria. The ORR was 22.89% (vs. 10% of historical control, p < 0.001) and the DCR was 80.72%. The median PFS and OS were 5.23 months (95% CI: 3.91–6.55 months) and 14.40 months (95% CI: 13.21–15.59 months), respectively. After matching with a balanced population in the docetaxel arm from the East Asia S-1 Trial in Lung Cancer, the weighted median PFS and OS were 7.90 months (vs. 2.89 months) and 19.37 months (vs. 12.52 months), respectively. Time to start of first subsequent therapy (TSFT) from first-line chemotherapy (TSFT > 9 months vs. TSFT ≤ 9 months) was an independent predictive factor of second-line PFS (8.7 months vs. 5.0 months, HR = 0.461, p = 0.049). The median OS in patients who achieved response was 23.5 months (95% CI: 11.8–31.6 months), which was significantly longer than those with stable disease (14.9 months, 95% CI: 12.9–19.4 months, p < 0.001) or progression (4.9 months, 95% CI: 3.2–9.5 months, p < 0.001). The most common adverse events were anemia (60.92%), nausea (55.17%), and leukocytopenia (33.33%).

Conclusions

S-1-based non-platinum combination had promising efficacy and safety in advanced NSCLC patients who had failed platinum doublet chemotherapy, suggesting that it could be a favorable second-line treatment option.
The temporal trend of women’s cancer in Changle, China and a migrant epidemiological study
Authors: Chen Yu , Song Mengjie , Zhang Yanyu , Yu Xingxing , Zou Shuqing , Zhu Pingxiu , Zhou Yulin , Yang Haomin
Published: March 2023

Background

Although the etiology of women’s cancer has been extensively studied in the last few decades, there is still little evidence comparing the temporal pattern of these cancers among different populations.

Methods

Cancer incidence and mortality data from 1988 to 2015 were extracted from the Changle Cancer Register in China, and cancer incidence data for Los Angeles were extracted from Cancer Incidence in Five Continents plus database. A Joinpoint regression model was used to analyze the temporal trends of incidence and mortality for breast, cervical, corpus uteri and ovarian cancers. The standardized incidence ratios were applied to compare the cancer risk across populations.

Results

An increasing trend of incidence rate for breast, cervical, corpus uteri and ovarian cancer was observed in Changle, although the rate leveled off for breast and cervical cancer after 2010, although not statistically significant. The mortality rate of breast and ovarian cancer was slightly increased during this period, while we found a decreased mortality of cervical cancer from 2010. The mortality of corpus uteri cancer showed a decreasing and then increasing trend. The incidence of breast, corpus uteri and ovarian cancer in Chinese American immigrants in Los Angeles was significantly higher than indigenous Changle Chinese and lower than Los Angeles whites. However, the incidence of cervical cancer in Chinese American immigrants shifted from significantly exceeding to lower than Changle Chinese.

Conclusion

The incidence and mortality of women’s cancers in Changle were generally on the rise, and this study concluded that environmental changes were important factors affecting the occurrence of these cancers. Appropriate preventive measures should be taken to control the occurrence of women’s cancers by addressing different influencing factors.
Pathological fracture due to primary bone lymphoma in a patient with a history of prostate cancer: A case report and review of literature
Authors: Bhakta Pooja , Hunzeker Zachary E. , Garcia Juan D. , Youssef Ayman , Grant Bradley J. , Alfattal Rasha , Weaver Dylan , Bhargava Peeyush , Rischall Ariel , Musunuru Tejo , Muthukumarana Palawinnage V. , Mallick Jayati , Lyapichev Kirill A.
Published: March 2023

Primary bone lymphoma (PBL) is a rare extranodal presentation within lymphomas and primary bone malignancies. Pathologic fracture (PF) is a common complication of metastatic bone disease but is, rarely, the presentation of a primary bone tumor. We report a case of an 83-year-old man with a history of untreated prostate cancer, presenting with atraumatic fracture of his left femur after months of intermittent pains and weight loss. Radiographic workup revealed a lytic lesion suspicious for PF secondary to metastatic prostate cancer; however, initial core biopsy results were inconclusive for malignancy. A complete blood count with differential and complete metabolic panel was within normal limits. During surgical fixation and nailing of the femur, a reaming biopsy was performed as a repeat measure and revealed diffuse large B-cell lymphoma. Staging with positron emission tomography and computed tomography found no evidence of lymphatic or visceral involvement and chemotherapy was promptly initiated. This case highlights the diagnostic workup challenges for PF secondary to PBL, especially in the setting of concurrent malignancy. Because of the non-specific presentation of a lytic lesion on imaging associated with atraumatic fracture, we highlight PBL as an important diagnostic consideration.
B cell M-CLL clones retain selection against replacement mutations in their immunoglobulin gene framework regions
Authors: Neuman Hadas , Arrouasse Jessica , Benjamini Ohad , Mehr Ramit , Kedmi Meirav
Published: March 2023

Introduction

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia, accounting for 30–40% of all adult leukemias. The dynamics of B-lymphocyte CLL clones with mutated immunoglobulin heavy chain variable region (IgHV) genes in their tumor (M-CLL) can be studied using mutational lineage trees.

Methods

Here, we used lineage tree-based analyses of somatic hypermutation (SHM) and selection in M-CLL clones, comparing the dominant (presumably malignant) clones of 15 CLL patients to their non-dominant (presumably normal) B cell clones, and to those of healthy control repertoires. This type of analysis, which was never previously published in CLL, yielded the following novel insights.

Results

CLL dominant clones undergo – or retain – more replacement mutations that alter amino acid properties such as charge or hydropathy. Although, as expected, CLL dominant clones undergo weaker selection for replacement mutations in the complementarity determining regions (CDRs) and against replacement mutations in the framework regions (FWRs) than non-dominant clones in the same patients or normal B cell clones in healthy controls, they surprisingly retain some of the latter selection in their FWRs. Finally, using machine learning, we show that even the non-dominant clones in CLL patients differ from healthy control clones in various features, most notably their expression of higher fractions of transition mutations.

Discussion

Overall, CLL seems to be characterized by significant loosening – but not a complete loss – of the selection forces operating on B cell clones, and possibly also by changes in SHM mechanisms.
ITGB1-mediated molecular landscape and cuproptosis phenotype induced the worse prognosis in diffuse gastric cancer
Authors: Zhu Xingyu , Chen Hao , Li Han , Ren Huicheng , Ye Chunshui , Xu Kang , Liu Jin , Du Fengying , Zhang Zihao , Liu Yuan , Xie Xiaozhou , Wang Mingfei , Ma Tianrong , Chong Wei , Shang Liang , Li Leping
Published: March 2023

Diffuse type gastric cancer was identified with relatively worse prognosis than other Lauren’s histological classification. Integrin β1 (ITGB1) was a member of integrin family which played a markedly important role in tumorigenesis and progression. However, the influence of ITGB1 in diffuse gastric cancer (DGC) remains uncertain. Here, we leveraged the transcriptomic and proteomic data to explore the association between ITGB1 expression and clinicopathologic information and biological process in DGC. Cell phenotype experiments combined with quantitative-PCR (q-PCR) and western blotting were utilized to identify the potential molecular mechanism underling ITGB1.Transcriptomics and proteomics both revealed that the higher ITGB1 expression was significantly associated with worse prognosis in DGC, but not in intestinal GC. Genomic analysis indicated that the mutation frequency of significantly mutated genes of ARID1A and COL11A1, and mutational signatures of SBS6 and SBS15 were markedly increased in the ITGB1 low expression subgroup. The enrichment analysis revealed diverse pathways related to dysregulation of ITGB1 in DGC, especially in cell adhesion, proliferation, metabolism reprogramming, and immune regulation alterations. Elevated activities of kinase-ROCK1, PKACA/PRKACA and AKT1 were observed in the ITGB1 high-expression subgroup. The ssGSEA analysis also found that ITGB1 low-expression had a higher cuproptosis score and was negatively correlated with key regulators of cuproptosis, including FDX1, DLAT, and DLST. We further observed that the upregulated expression of mitochondrial tricarboxylic acid (TCA) cycle in the ITGB1 low-expression group. Reduced expression of ITGB1 inhibited the ability of cell proliferation and motility and also potentiated the cell sensitive to copper ionophores via western blotting assay. Overall, this study revealed that ITGB1 was a protumorigenic gene and regulated tumor metabolism and cuproptosis in DGC.
Lymphocyte-activating gene 3 expression in tumor cells predicts immune checkpoint inhibitor response in triple negative breast cancer
Authors: Kim Ji-Yeon , Kim Jeehyun , Cho Eun Yoon , Park Yeon Hee , Ahn Jin Seok , Kim Kyoung-Mee , Im Young-Hyuck
Published: March 2023

Introduction

Immune checkpoint inhibitor (ICI) is one of the standard treatment strategies in triple negative breast cancer (TNBC). However, the benefit of ICI with chemotherapy is limited in metastatic TNBC. In this study, we evaluated the effect of PD-L1 and LAG-3 expression on tissue microenvironment of mTNBC treated with ICI.

Methods

We reviewed representative formalin-fixed paraffin embedded specimens from metastatic or archival tumor tissues of TNBCs who treated with PD-1/PD-L1 inhibitors in metastatic setting. We used the Opal multiplex Detection kit with six antibodies (anti-PD-L1, anti-LAG-3, anti-CD68, anti-panCK, anti-CD8, anti-CD107a/LAMP antibody).

Results

We evaluated the association between LAG-3+cells and survival outcome regarding CK expression. Stromal LAG-3+/CK+ and LAG-3+/CK- cells were not associated with ICI-progression free survival(PFS) (P=0.16). However, LAG-3+ cell distributions in the tumor area impacted on ICI-PFS. A high density of LAG-3+CK+ cells was associated with shorter ICI-PFS compared with low densities of both LAG-3+CK+ and LAG-3+CK- cells (1.9 vs. 3.5 months). In addition, a high density of LAG-3+CK- cells had a relatively longer ICI-PFS compared with other groups (P=0.01). In terms of total area, the pattern of densities of LAG-3+CK+ cells and LAG-3+CK- cells were similar to those in the tumor area In addition, ICI-PFS of LAG-3+CK- and LAG-3+CK+ cell densities in the total area was equal to that in the tumor area.

Discussion

In conclusion, our findings revealed tumor-intrinsic LAG-3 expression was the resistance mechanism toward PD-1/PD-L1 inhibitors in mTNBCs. Multivariate analysis also suggested that LAG-3 expression in tumor cells was an independent predictive biomarker.