bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep learning to estimate durable clinical benefit and prognosis from patients with non-small cell lung cancer treated with PD-1/PD-L1 blockade
Authors: Peng Jie , Zhang Jing , Zou Dan , Xiao Lushan , Ma Honglian , Zhang Xudong , Li Ya , Han Lijie , Xie Baowen
Published: November 2022

Different biomarkers based on genomics variants have been used to predict the response of patients treated with PD-1/programmed death receptor 1 ligand (PD-L1) blockade. We aimed to use deep-learning algorithm to estimate clinical benefit in patients with non-small-cell lung cancer (NSCLC) before immunotherapy. Peripheral blood samples or tumor tissues of 915 patients from three independent centers were profiled by whole-exome sequencing or next-generation sequencing. Based on convolutional neural network (CNN) and three conventional machine learning (cML) methods, we used multi-panels to train the models for predicting the durable clinical benefit (DCB) and combined them to develop a nomogram model for predicting prognosis. In the three cohorts, the CNN achieved the highest area under the curve of predicting DCB among cML, PD-L1 expression, and tumor mutational burden (area under the curve [AUC] = 0.965, 95% confidence interval [CI]: 0.949–0.978, P< 0.001; AUC =0.965, 95% CI: 0.940–0.989, P< 0.001; AUC = 0.959, 95% CI: 0.942–0.976, P< 0.001, respectively). Patients with CNN-high had longer progression-free survival (PFS) and overall survival (OS) than patients with CNN-low in the three cohorts. Subgroup analysis confirmed the efficient predictive ability of CNN. Combining three cML methods (CNN, SVM, and RF) yielded a robust comprehensive nomogram for predicting PFS and OS in the three cohorts (each P< 0.001). The proposed deep-learning method based on mutational genes revealed the potential value of clinical benefit prediction in patients with NSCLC and provides novel insights for combined machine learning in PD-1/PD-L1 blockade.
What's next for size-sound symbolism?
Authors: Ekström Axel G.
Published: November 2022

This text reviews recent research in phonetic size-sound symbolism – non-arbitrary attributions of size properties to speech acoustic properties. Evidence from a wide range of research works is surveyed, and recent findings from research on the relationships between fundamental frequency, vowel articulation, consonant articulation, phonation type, mora count, and phonemic position, are discussed. It is argued that a satisfactory explanatory model of phonetic size-sound symbolism should meet two criteria: they should be able to explain both (1) the relationship between size and speech acoustics (Association criterion), and (2) the inconsistent findings observed across languages in the relevant literature (the Inconsistency criterion). Five theories are briefly discussed: The frequency code, Embodied cognition, Sound-meaning bootstrapping, Sapir-Whorf hypotheses, and Stochastic drift. It is contended that no currently available explanatory model of size-sound symbolism adequately meets both criteria (1) and (2), but that a combination of perspectives may provide much of the necessary depth. Future directions are also discussed.
Seasonal near-surface hypoxia in a temperate fjord in Clayoquot Sound, British Columbia
Authors: Rosen Sarah , Bianucci Laura , Jackson Jennifer M. , Hare Alex , Greengrove Cheryl , Monks Rowen , Bartlett Mackenzie , Dick Jared
Published: November 2022

While fjords often have low oxygen concentrations in their deep waters, this research identified seasonal, near-surface hypoxia (≤ 2 mL L-1 or 2.9 mg L-1) through a year-long monthly time series in Clayoquot Sound, British Columbia. Temperature, salinity, and oxygen data were collected monthly in the upper 50 m at three stations in Herbert Inlet from June 2020 to July 2021, marking the first time series of its kind in a Clayoquot Sound fjord. Hypoxic conditions were shallowest (minimum depth of 12 m) and most intensified in summer; near-surface hypoxia was recorded at one or more stations in all months except in winter. Considering that many local marine species, including wild Pacific salmon, experience adverse effects at oxygen concentrations much higher than the hypoxic threshold, we note that 50 to 100% of the upper 50 m of Herbert Inlet consistently presented low oxygen concentrations (defined here as a guideline as ≤ 4.9 mL L-1 or 6.9 mg L-1) during the 14-month study period. Previous observations collected sporadically since May 1959 confirmed the presence of hypoxic conditions in the past. These findings suggest that long-term, multidisciplinary studies are needed to understand and predict the impact of hypoxia and deoxygenation on wild salmon stocks as climate changes.
Lack of panmixia of Bothnian Bay vendace - Implications for fisheries management
Authors: López María-Eugenia , Bergenius Nord Mikaela , Kaljuste Olavi , Wennerström Lovisa , Hekim Zeynep , Tiainen Joni , Vasemägi Anti
Published: November 2022

Overexploitation of fisheries is recognized as a major environmental and socioeconomic problem that threats biodiversity and ecosystem functioning. Inappropriate management policies of fish stocks have been applied as a consequence of inadequate characterization of subtle genetic structure in many fish species. In this study, we aim to assess the extent of genetic differentiation and structure of vendace (Coregonus albula) collected from eight locations in the Bothnian Bay, the northernmost part of the Baltic Sea. Specifically, we test if this species forms a single panmictic population or is divided into several genetically distinct units. We used restriction site-associated DNA sequencing (RAD-seq) to identify 21,792 SNPs based on 266 individuals. We identified a clear pattern of genetic differentiation between River Kalix and the other sampling locations, and a weak structuring between samples from Swedish and Finnish coast. Outlier analysis detected 41 SNPs putatively under divergent selection, mainly reflecting the divergence between River Kalix and the other samples. The outlier SNPs were located within or near 25 genes, including voltage-dependent calcium channel subunit alpha-2 (CACNA2D2), cadherin 26 (CDH26) and carbonic anhydrase 4-like (CA4) that have earlier been associated with salt-tolerance and salinity stress. Our study provides the first genome-wide perspective on genetic structuring of Baltic Sea vendace and rejects the hypothesis of panmixia in the Bothnian Bay. As such, our work demonstrates the power of RAD-sequencing to detect low but significant genetic structuring relevant for fisheries management.
The aquatic particle number quandary
Authors: Bochdansky Alexander B. , Huang Huanqing , Conte Maureen H.
Published: November 2022

Optical surveys of aquatic particles and their particle size spectra have become important tools in studies of light propagation in water, classification of water masses, and the dynamics of trophic interactions affecting particle aggregation and flux. Here, we demonstrate that typical settings used in image analysis vastly underestimate particle numbers due to the particle – gel continuum. Applying a wide range of threshold values to change the sensitivity of our detection system, we show that macrogels cannot be separated from more dense particles, and that a true particle number per volume cannot be ascertained; only relative numbers in relation to a defined threshold value can be reported. A quandary thus presents itself between choosing a detection threshold low enough to accurately record orders of magnitude more particles on one hand or selecting a higher threshold to yield better image quality of plankton on the other. By observing the dynamics of coagulation and dissolution steps unique to cation-bridged gels abundant in aquatic systems, we find naturally occurring gels, and microscopic particles attached to them, to cause the ill-defined particle numbers. In contrast, the slopes in particle number spectra remained largely unaffected by varying sensitivity settings of the image analysis. The inclusion of fainter particles that are not typically captured by imaging systems provides a window into the true microscale spatial heterogeneity at scales relevant to small plankton organisms and processes that are dependent on particle density such as surface-associated chemical reactions as well as particle coagulation and aggregation dynamics.
Melon/cowpea intercropping pattern influenced the N and C soil cycling and the abundance of soil rare bacterial taxa
Authors: Cuartero Jessica , Pascual Jose Antonio , Vivo Juana-María , Özbolat Onurcan , Sánchez-Navarro Virginia , Weiss Julia , Zornoza Raúl , Martínez-Mena María , García Eloisa , Ros Margarita
Published: November 2022

The high use of pesticides, herbicides, and unsustainable farming practices resulted in losses of soil quality. Sustainable farming practices such as intercropping could be a good alternative to traditional monocrop, especially using legumes such as cowpea (Vigna unguiculata L. Walp). In this study, different melon and cowpea intercropping patterns (melon mixed with cowpea in the same row (MC1); alternating one melon row and one cowpea row (MC2); alternating two melon rows and one cowpea row (MC3)) were assayed to study the intercropping effect on soil bacterial community through 16S rRNA region in a 3-year experiment. The results indicated that intercropping showed high content of total organic carbon, total nitrogen and ammonium, melon yield, and bacterial diversity as well as higher levels of beneficial soil microorganisms such a Pseudomonas, Aeromicrobium, Niastella, or Sphingomonas which can promote plant growth and plant defense against pathogens. Furthermore, intercropping showed a higher rare taxa diversity in two (MC1 and MC2) out of the three intercropping systems. In addition, N-cycling genes such as nirB, nosZ, and amoA were more abundant in MC1 and MC2 whereas the narG predicted gene was far more abundant in the intercropping systems than in the monocrop at the end of the 3-year experiment. This research fills a gap in knowledge about the importance of soil bacteria in an intercropping melon/cowpea pattern, showing the benefits to yield and soil quality with a decrease in N fertilization.
Gut microbiota-generated short-chain fatty acids are involved in para-chlorophenylalanine-induced cognitive disorders
Authors: Liu Yanbo , Li Zhen , Sun Tianning , He Zhigang , Xiang Hongbing , Xiong Jun
Published: November 2022

Neurocognitive disorders (NCDs) include complex and multifactorial diseases that affect many patients. The 5-hydroxytryptamine (5-HT) neuron system plays an important role in NCDs. Existing studies have reported that para-chlorophenylalanine (PCPA), a 5-HT scavenger, has a negative effect on cognitive function. However, we believe that PCPA may result in NCDs through other pathways. To explore this possibility, behavioral tests were performed to evaluate the cognitive function of PCPA-treated mice, suggesting the appearance of cognitive dysfunction and depression-like behavior. Furthermore, 16S rRNA and metabolomic analyses revealed that dysbiosis and acetate alternation could be related to PCPA-induced NCDs. Our results suggest that not only 5-HT depletion but also dysbiosis and acetate alternation contributed to PCPA-related NCDs. Specifically, the latter promotes NCDs by reducing short-chain fatty acid levels. Together, these findings provide an alternative perspective on PCPA-induced NCDs.
Unraveling the effects of sulfamethoxazole on the composition of gut microbiota and immune responses in Stichopus variegatus
Authors: Tan Chunming , Zhao Wang , Wen Weigeng , Chen Xu , Ma Zhenhua , Yu Gang
Published: November 2022

The aim of this work was to reveal the changes in gut microbiota composition and immune responses of sea cucumber (Stichopus variegatus) after being affected by different doses of sulfamethoxazole. In this study, the bacterial 16S rRNA of gut microbiota were analyzed by high-throughput sequencing, and the activities of immune enzymes [lysozyme (LZM), phenoloxidase (PO), alkaline phosphatase (AKP), and acid phosphatase (ACP)] in the gut of S. variegatus were determined. The results showed that the gut microbiota presented a lower richness in the antibiotic treatment groups compared with the control group, and there were significant differences among the dominant bacteria of different concentration treatments. At the genus level, the abundance of Escherichia, Exiguobacterium, Acinetobacter, Pseudomonas, and Thalassotalea were significantly decreased in the 3 mg/L treatment group, while Vibrio was significantly increased. Furthermore, the 6 mg/L treatment group had less effect on these intestinal dominant bacteria, especially Vibrio. The changes in relative abundance of Vibrio at the species level indicated that lower concentrations of sulfamethoxazole could enhance the enrichment of Vibrio mediterranei and Vibrio fortis in S. variegatus more than higher concentrations of sulfamethoxazole. Meanwhile, the 3 mg/L treatment group significantly increased the activities of PO, AKP, and ACP, and decreased the activity of LZM. These results suggested that lower doses of sulfamethoxazole have a greater effect on the gut microbiota composition and immune responses in S. variegatus and may increase the risk of host infection.
Antibacterial activity of bioactive compounds extracted from red kidney bean (Phaseolus vulgaris L.) seeds against multidrug-resistant Enterobacterales
Authors: Ebrahim Azhar E. , Abd El-Aziz Norhan K. , Elariny Eman Y. T. , Shindia Ahmed , Osman Ali , Hozzein Wael N. , Alkhalifah Dalal Hussien M. , El-Hossary Dalia
Published: November 2022

In the present study, biologically active compounds such as phenolic-rich extract (PRE), 7S globulin (vicilin), and 11S globulin (legumin) from red kidney bean (Phaseolus vulgaris L.) seeds were extracted and evaluated as antibacterial agents against multidrug-resistant (MDR) Enterobacterales isolated from both animal and human sources. The overall occurrence rate of Enterobacterales was 43.6%, which significantly differed between animal (38.75%) and human (56.67%) sources. Antimicrobial susceptibility testing revealed that Enterobacterales isolates exhibited full resistance (100%) to amoxicillin-clavulanic acid, followed by ampicillin (75.44%), erythromycin (71.93%), cefoxitin (70.18%), amoxicillin (66.66%), ceftriaxone (64.91%), and trimethoprim/sulfamethoxazole (56.14%). Worthy of note, 97.92% of Enterobacterales isolates were MDR. The total phenolic contents (TPC; 53 ± 2 mg GAE g-1) and total flavonoid contents (TFC; 26 ± 1 mg QE g-1) were recorded. The major phenolic and flavonoid components were catechol (17.63 μg/mL) and hesperidin (11.37 μg/mL), respectively. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) was performed to detect the 7S and 11S globulin‘s molecular mass. The data revealed that red kidney bean protein isolate (KPI) includes two major portions: 7S and 11S globulins. The bioactive compounds of Phaseolus vulgaris were investigated for their antibacterial activities against Enterobacterales for the first time. The protein component (MIC = 0.125 – 2 μg/mL; 53.85%) and its 7S and 11S globulin subunits (MIC = 0.5 – 2 μg/mL; 30.77% each) were the most potent extracts, whereas the methanolic extract was the least effective one (MIC = 2 μg/mL; 15.38%). The results displayed the potential of protein bioactive compounds as a hopeful candidate for enhancing future medication plans for the treatment of Enterobacterales originating from animal and human sources.
The role of ageing and oxidative stress in intervertebral disc degeneration
Authors: Wen Pengfei , Zheng Bolong , Zhang Binfei , Ma Tao , Hao Linjie , Zhang Yumin
Published: November 2022

Intervertebral disc degeneration (IDD) is the primary cause of intervertebral disc (IVD) disease. With the increased ageing of society, an increasing number of patients are plagued by intervertebral disc disease. Ageing not only accelerates the decreased vitality and functional loss of intervertebral disc cells but also increases intracellular oxidative stress. Moreover, the speed of intervertebral disc ageing is also linked to high levels of reactive oxygen species (ROS) production. Not only is the production of ROS increased in ageing intervertebral disc cells, but antioxidant levels in degenerative intervertebral discs also decrease. In addition to the intervertebral disc, the structural components of the intervertebral disc matrix are vulnerable to oxidative damage. After chronic mitochondrial dysfunction, ROS can be produced in large quantities, while autophagy can eliminate these impaired mitochondria to reduce the production of ROS. Oxidative stress has a marked impact on the occurrence of IDD. In the future, IDD treatment is aiming to improve oxidative stress by regulating the redox balance in intervertebral disc cells. In summary, ageing and oxidative stress promote the degeneration of IVD, but further basic and clinical trials are needed to determine how to treat oxidative stress. At present, although there are many in-depth studies on the relationship between oxidative stress and degeneration of intervertebral disc cells, the specific mechanism has not been elucidated. In this paper, the main causes of intervertebral disc diseases are studied and summarized, and the impact of oxidative stress on intervertebral disc degeneration is studied.
Potential blood biomarkers for chronic traumatic encephalopathy: The multi-omics landscape of an observational cohort
Authors: Ge Xintong , Guo Mengtian , Li Meimei , Zhang Shishuang , Qiang Junlian , Zhu Luoyun , Cheng Lu , Li Wenzhu , Wang Yan , Yu Jinwen , Yin Zhenyu , Chen Fanglian , Tong Wen , Lei Ping
Published: November 2022

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with exposure to repetitive head impacts, which is susceptible in elderly people with declined mobility, athletes of full contact sports, military personnel and victims of domestic violence. It has been pathologically diagnosed in brain donors with a history of repetitive mild traumatic brain injury (rmTBI), but cannot be clinically diagnosed for a long time. By the continuous efforts by neuropathologists, neurologists and neuroscientists in recent 10 years, an expert consensus for the diagnostic framework of CTE was proposed in 2021 funded by the National Institute of Neurological Disorders and Stroke. The new consensus contributes to facilitating research in the field. However, it still needs to incorporate in vivo biomarkers to further refine and validate the clinical diagnostic criteria. From this, a single-center, observational cohort study has been being conducted by Tianjin Medical University General Hospital since 2021. As a pilot study of this clinical trial, the present research recruited 12 pairs of gender- and age-matched rmTBI patients with healthy subjects. Their blood samples were collected for exosome isolation, and multi-omics screening to explore potential diagnostic biomarkers in blood and its exosomes. The expression level of CHL1 protein, KIF2A mRNA, LIN7C mRNA, miR-297, and miR-1183 in serum and exosomes were found to be differentially expressed between groups. Besides, serum and exosomal CHL1, KIF2A, and miR-1183, as well as exosomal miR-297 were further verified as potential biomarkers for CTE by low-throughput assays. They are expected to contribute to establishing a novel set of CTE diagnostic signatures with classic neurodegenerative indicators in our future study, thereby updating the consensus diagnostic criteria for CTE by incorporating new evidence of the in vivo biomarkers.
A two-year longitudinal study of retinal vascular impairment in patients with amnestic mild cognitive impairment
Authors: Criscuolo Chiara , Cennamo Gilda , Montorio Daniela , Carotenuto Antonio , Migliaccio Miriana , Moccia Marcello , Salvatore Elena , Lanzillo Roberta , Costagliola Ciro , Morra Vincenzo Brescia
Published: November 2022

Objective

To evaluate the relation between retinal vascular impairment and cognitive decline in patients with amnestic mild cognitive impairment (aMCI) over time.

Methods

Spectral domain-optical coherence tomography (SD-OCT) and OCT angiography study was performed in aMCI patients over 2 years follow-up and compared to baseline.

Results

Thirty-eight eyes from 19 aMCI patients were evaluated. Structural and vascular OCT measures were reduced at follow-up except for vessel density (VD) of the choriocapillaris, unchanged, and foveal avascular zone, which was increased; no changes in any parameter were found in 18 age-matched healthy controls. Overall, these findings were confirmed when patients were evaluated separately according to progression to dementia. Only non-converters to dementia showed significant VD reduction in the deep capillary plexuses (coeff. β = −4.20; p < 0.001), may be for an initial massive VD depletion becoming less evident with progression of the disease. MMSE reduction was associated with a higher ganglion cell complex reduction (coeff. β = 0.10; p = 0.04) and a higher VD reduction in the radial peripapillary capillary (RPC) plexus (coeff. β = 0.14; p = 0.02) in the whole patient group, while it was associated with a higher VD reduction only in RPC plexus in converters (coeff. β = 0.21; p < 0.001).

Conclusion

Our data shows vascular impairment progression in the inner retina of aMCI patients and support the hypothesis that vascular changes may contribute to the onset and progression of Alzheimer’s disease. Other follow-up studies, with a larger number of patients, are needed to better define VD as a potential biomarker.
p53-dependent c-Fos expression is a marker but not executor for motor neuron death in spinal muscular atrophy mouse models
Authors: Buettner Jannik M. , Sowoidnich Leonie , Gerstner Florian , Blanco-Redondo Beatriz , Hallermann Stefan , Simon Christian M.
Published: November 2022

The activation of the p53 pathway has been associated with neuronal degeneration in different neurological disorders, including spinal muscular atrophy (SMA) where aberrant expression of p53 drives selective death of motor neurons destined to degenerate. Since direct p53 inhibition is an unsound therapeutic approach due carcinogenic effects, we investigated the expression of the cell death-associated p53 downstream targets c-fos, perp and fas in vulnerable motor neurons of SMA mice. Fluorescence in situ hybridization (FISH) of SMA motor neurons revealed c-fos RNA as a promising candidate. Accordingly, we identified p53-dependent nuclear upregulation of c-Fos protein in degenerating motor neurons from the severe SMNΔ7 and intermediate Smn2B/– SMA mouse models. Although motor neuron-specific c-fos genetic deletion in SMA mice did not improve motor neuron survival or motor behavior, p53-dependent c-Fos upregulation marks vulnerable motor neurons in different mouse models. Thus, nuclear c-Fos accumulation may serve as a readout for therapeutic approaches targeting neuronal death in SMA and possibly other p53-dependent neurodegenerative diseases.
Artificial intelligence insights into hippocampal processing
Authors: Wirtshafter Hannah S. , Wilson Matthew A.
Published: November 2022

Advances in artificial intelligence, machine learning, and deep neural networks have led to new discoveries in human and animal learning and intelligence. A recent artificial intelligence agent in the DeepMind family, muZero, can complete a variety of tasks with limited information about the world in which it is operating and with high uncertainty about features of current and future space. To perform, muZero uses only three functions that are general yet specific enough to allow learning across a variety of tasks without overgeneralization across different contexts. Similarly, humans and animals are able to learn and improve in complex environments while transferring learning from other contexts and without overgeneralizing. In particular, the mammalian extrahippocampal system (eHPCS) can guide spatial decision making while simultaneously encoding and processing spatial and contextual information. Like muZero, the eHPCS is also able to adjust contextual representations depending on the degree and significance of environmental changes and environmental cues. In this opinion, we will argue that the muZero functions parallel those of the hippocampal system. We will show that the different components of the muZero model provide a framework for thinking about generalizable learning in the eHPCS, and that the evaluation of how transitions in cell representations occur between similar and distinct contexts can be informed by advances in artificial intelligence agents such as muZero. We additionally explain how advances in AI agents will provide frameworks and predictions by which to investigate the expected link between state changes and neuronal firing. Specifically, we will discuss testable predictions about the eHPCS, including the functions of replay and remapping, informed by the mechanisms behind muZero learning. We conclude with additional ways in which agents such as muZero can aid in illuminating prospective questions about neural functioning, as well as how these agents may shed light on potential expected answers.
Solute carrier transporter disease and developmental and epileptic encephalopathy
Authors: Gan Yajing , Wei Zihan , Liu Chao , Li Guoyan , Feng Yan , Deng Yanchun
Published: November 2022

The International League Against Epilepsy officially revised its classification in 2017, which amended “epileptic encephalopathy” to “developmental and epileptic encephalopathy”. With the development of genetic testing technology, an increasing number of genes that cause developmental and epileptic encephalopathies are being identified. Among these, solute transporter dysfunction is part of the etiology of developmental and epileptic encephalopathies. Solute carrier transporters play an essential physiological function in the human body, and their dysfunction is associated with various human diseases. Therefore, in-depth studies of developmental and epileptic encephalopathies caused by solute carrier transporter dysfunction can help develop new therapeutic modalities to facilitate the treatment of refractory epilepsy and improve patient prognosis. In this article, the concept of transporter protein disorders is first proposed, and nine developmental and epileptic encephalopathies caused by solute carrier transporter dysfunction are described in detail in terms of pathogenesis, clinical manifestations, ancillary tests, and precise treatment to provide ideas for the precise treatment of epilepsy.
Association fiber tracts related to Broca’s area: A comparative study based on diffusion spectrum imaging and fiber dissection
Authors: Wu Yupeng , Liu Jihui , Yu Guoning , Jv Ronghui , Wang Yibao , Zang Peizhuo
Published: November 2022

Broca’s area, made up of Brodmann areas (BA) 44 and 45 in the ventrolateral frontal region, is associated with language production and articulation. A comprehensive network analysis of Broca’s area is necessary for understanding language function, which is still lacking. In this study, we attempted to investigate the association fiber tracts related to Broca’s area using both diffusion spectrum imaging (DSI) and postmortem fiber dissection. DSI was performed on 10 healthy subjects and an atlas comprising the average data of 842 healthy subjects from the Human Connectome Project. Fiber dissection was implemented in 10 cerebral hemispheres of cadaver donors. The following five association fiber tracts related to Broca’s area were identified: first, the distinct fasciculus of the inferior fronto-occipital fasciculus (IFOF), from Broca’s area (BA44, BA45) and pars orbitalis (BA47) to the parietal and occipital lobes; second, the ventral superior longitudinal fasciculus (SLF-III), from the supramarginal gyrus (BA40) to the ventral precentral gyrus (PreG, BA6) and posterior Broca’s area (BA44); third, the arcuate fascicle (AF), from the superior, middle, and inferior temporal gyrus (BA20, BA21, BA22) to Broca’s area (BA44, BA45) and ventral PreG; fourth, the frontal aslant tract (FAT), from Broca’s area (BA44, BA45) to the lateral superior frontal gyrus (SFG), medial SFG, and supplementary motor area (BA6, BA8, BA9); and fifth, the frontal longitudinal fasciculus (FLF), a novel intralobar frontal association fiber tract, from the anterior part of the middle frontal gyrus (MFG, BA46) and Broca’s area (BA45) to the caudal MFG (BA8), caudal SFG, and dorsal PreG (BA6). Moreover, compared with the left FAT, the right FAT covered almost the entire inferior frontal gyrus (BA44, BA45, BA47). The cross validation between DSI and fiber dissection revealed a good consistence in the association fiber tracts of Broca’s area. Combining DSI and fiber dissection, this study first identified five association fiber tracts related to Broca’s area and characterized their structure and anatomy comprehensively. The frameworks provided key elements for functional research in Broca’s area.
Neptunium mononitride as a target material for Pu-238 production
Authors: Peruski Kathryn M.
Published: November 2022

Deep space exploration requires specialized sources for both thermal and power applications. Radioactive decay heat of plutonium-238 (238Pu) provides these sources in the form of radioisotope thermoelectric generators (RTGs). The238Pu is producedvianeutron capture reaction involving neptunium-237 (237Np) target material. Continual optimization of237Np target materials and evaluation of potential alternative targets for production of238Pu RTGs are advantageous for meeting ongoing space power system resource requirements. Current production of238Pu for RTGs for the United States space program utilizes neptunium dioxide (237NpO2) targets; however, the use of neptunium mononitride (237NpN) presents an opportunity to increase the mass of237Np per target compared to the dioxide form, as well as increase the thermal conductivity of the target. To assess the viability of a237NpN target material, the material chemistry must be thoroughly evaluated, including synthesis methods and dissolution and reprocessing schemes. This review presents a summary of synthesis pathways for237NpN based on published literature on actinide mononitrides. Specific literature on237NpN is limited, necessitating evaluation of other actinide systems to gather parallels. This suggests a need for additional experimental studies on237NpN. A particular limitation in the existing literature is a lack of information on the differences in material characteristics, such as morphology, particle size, and trace chemical impurities, as a function of synthesis method. These parameters may affect subsequent reactor performance or dissolution of irradiated targets. The evaluation of existing literature is presented with a focus on the efficacy of237NpN targets for238Pu production.
Gut microbial response to host metabolic phenotypes
Authors: Hou Jinliang , Xiang Jianguo , Li Deliang , Liu Xinhua , Pan Wangcheng
Published: November 2022

A large number of studies have proved that biological metabolic phenotypes exist objectively and are gradually recognized by humans. Gut microbes affect the host’s metabolic phenotype. They directly or indirectly participate in host metabolism, physiology and immunity through changes in population structure, metabolite differences, signal transduction and gene expression. Obtaining comprehensive information and specific identification factors associated with gut microbiota and host metabolic phenotypes has become the focus of research in the field of gut microbes, and it has become possible to find new and effective ways to prevent or treat host metabolic diseases. In the future, precise treatment of gut microbes will become one of the new therapeutic strategies. This article reviews the content of gut microbes and carbohydrate, amino acid, lipid and nucleic acid metabolic phenotypes, including metabolic intermediates, mechanisms of action, latest research findings and treatment strategies, which will help to understand the relationship between gut microbes and host metabolic phenotypes and the current research status.
Waist-to-height ratio is a simple and practical alternative to waist circumference to diagnose metabolic syndrome in type 2 diabetes
Authors: Ma Yi-Lin , Jin Chun-Hua , Zhao Cui-Chun , Ke Jiang-Feng , Wang Jun-Wei , Wang Yu-Jie , Lu Jun-Xi , Huang Gao-Zhong , Li Lian-Xi
Published: November 2022

Background

As an indicator of abdominal obesity, waist circumference (WC) varied with race and gender in diagnosing metabolic syndrome (MetS). Therefore, it is clinically important to find an alternative indicator of abdominal obesity independent of these factors to diagnose MetS. Our aims were to evaluate the association between waist-to-height ratio (WHtR) and MetS and further determine whether WHtR could be used as a simple and practical alternative to WC to diagnose MetS in patients with type 2 diabetes mellitus (T2DM).

Methods

This cross-sectional, real-world study recruited 8488 hospitalized T2DM patients including 3719 women (43.8%) aged from 18 to 94 years and 4769 men (56.2%) aged from 18 to 91 years. A WHtR cut-off of 0.52 was used to diagnose MetS in both men and women T2DM patients based on our previous study. The association of WHtR with MetS in T2DM patients was analyzed by binary logistic regression. The consistency of two diagnostic criteria for MetS according to WC and WHtR was determined by Kappa test.

Results

The prevalence of MetS according to WHtR was 79.4% in women and 68.6% in men T2DM patients, which was very close to the prevalence of MetS according to WC in both women (82.6%) and men (68.3%). The prevalence of MetS diagnosed by WC in both men and women with WHtR ≥ 0.52 was significantly higher than in those with WHtR < 0.52 after adjustment for age and duration of diabetes (89.2 vs. 38.7% for men; 92.8 vs. 57.4% for women; respectively, all p < 0.001). Binary logistic regression analysis displayed that after adjusting for confounding factors, WHtR was significantly associated with the presence of MetS in both men and women (men: OR = 4.821, 95% CI: 3.949–5.885; women: OR = 3.096, 95% CI: 2.484–3.860; respectively, all p < 0.001). Kappa test revealed that there was an excellent consistency between the diagnosis of MetS based on WC and on WHtR in T2DM patients (men: kappa value = 0.929, 95% CI: 0.918–0.940; women: kappa value = 0.874, 95% CI: 0.854–0.894; total: kappa value = 0.911, 95% CI: 0.901–0.921; respectively, all p < 0.001).

Conclusion

WHtR is independently associated with the presence of MetS and can be used as a simple and practical alternative to WC to diagnose MetS regardless of gender in T2DM patients.
Meta-analysis of the diagnostic value of 18F-FDG PET/CT in the recurrence of epithelial ovarian cancer
Authors: Wang Xiaoyan , Yang Lifeng , Wang Yan
Published: November 2022

Background

Ovarian cancer is the leading cause of cancer-related death among gynecologic malignancies. With much evidence suggesting that 18F-FDG PET/CT may be an excellent imaging test for the diagnosis of epithelial ovarian cancer recurrence, we conducted a systematic review and meta-analysis to summarize relevant studies and evaluate the accuracy and application value of 18F-FDG PET/CT in the diagnosis of recurrence of epithelial ovarian cancer.

Materials and methods

Clinical trials of 18F-FDG PET/CT for the diagnosis of recurrence of epithelial ovarian cancer were systematically searched in PubMed, Embase, Cochrane Library, Web of Science and OVID database. The relevant literature was searched until May 22, 2022. Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used to evaluate the quality of the included original studies, and the meta-analysis was performed using a bivariate mixed-effects model and completed in Stata 15.0.

Results

A total of 17 studies on 18F-FDG PET/CT for the diagnosis of epithelial ovarian cancer recurrence were included in this systematic review, involving 639 patients with epithelial ovarian cancer. Meta-analysis showed that the sensitivity, specificity and area under the curve of 18F-FDG PET/CT for the diagnosis of epithelial ovarian cancer recurrence were 0.88 (95% CI: 0.79 - 0.93), 0.89 (95% CI: 0.72 - 0.96) and 0.94 (95% CI: 0.91- 0.96), respectively. Subgroup analysis showed higher diagnostic efficacy in prospective studies than in retrospective studies, and no significant publication bias was observed in Deeks’ funnel plot, with sensitivity analysis revealing the stability of results. Meta regression shows that the heterogeneity of this study comes from study type.

Conclusion

18F-FDG PET/CT has good diagnostic value in the recurrence of epithelial ovarian cancer.
Relationship between copper and immunity: The potential role of copper in tumor immunity
Authors: Cheng Fu , Peng Geng , Lu Yan , Wang Kang , Ju Qinuo , Ju Yongle , Ouyang Manzhao
Published: November 2022

Copper is an essential trace element in an organism, and changes in copper levels in vivo often indicate a diseased state. Copper and immunity have been discussed since the last century, with copper deficiency significantly affecting the development and function of the immune system, such as increased host susceptibility to various pathogens, decreased number and impaired function of neutrophils, reduced antibacterial activity of macrophages, decreased proliferation of splenocytes, impaired B cell ability to produce antibodies and impaired function of cytotoxic T lymphocyte and helper T cells. In the past 20 years, some studies have shown that copper ions are related to the development of many tumors, including lung cancer, acute lymphoid leukaemia, multiple myeloma and other tumors, wherein copper ion levels were significantly elevated, and current studies reveal that copper ions are involved in the development, growth and metastasis of tumors through various pathways. Moreover, recent studies have shown that copper ions can regulate the expression of PD-L1, thus, attention should be paid to the important role of copper in tumor immunity. By exploring and studying copper ions and tumor immunity, new insights into tumor immunity could be generated and novel therapeutic approaches to improve the clinical prognosis of patients can be provided.
Clinicopathologic features, prognostic factors, and outcomes of visceral sarcomas: A retrospective 12-year single-center study
Authors: Yang Songwei , Liao Zhichao , Li Ting , Liu Haotian , Ren Zhiwu , Wu Haixiao , Zhao Jun , Teng Sheng , Xing Ruwei , Yang Yun , Yang Jilong
Published: November 2022

Background

Visceral sarcomas are a rare form of soft tissue sarcoma. This study aimed to evaluate the survival and prognostic factors and effective treatments for visceral sarcomas.

Methods

All patients with visceral sarcoma referred to our center between January 2010 and December 2021 were retrospectively analyzed. The Kaplan-Meier method and a log-rank test were used for survival analysis.

Results

A total of 53 patients with visceral sarcoma were analyzed in this study with the median age at diagnosis of 57 (range, 24-77) years. Among them, 37 (69.8%) and 16 (30.2%) patients had localized and metastatic diseases at the initial presentation, respectively, and 44 patients underwent surgical resection. The median follow-up, event-free survival (EFS) and overall survival (OS) were 63.0 (range, 2-130), 42.0 months (95% confidence interval [CI] 10.879-73.121) and 45.0 months (95% CI 9.938-80.062), respectively. The 5-year EFS and OS rates were 44% and 46%, respectively. Univariate analysis of prognostic indicators illustrated that metastasis at presentation, surgery, surgical margin and the types of surgery were significantly associated with OS and EFS. In this study, combined chemotherapy or radiotherapy had no effects on EFS and OS.

Conclusion

Primary visceral sarcoma is an uncommon and aggressive malignant tumor with a higher rate of local recurrence. In the largest cohort of visceral sarcomas in China to date, we identified metastases at presentation, surgery, surgical margin, and the types of surgery as independent predictors of survival. The combination of chemotherapy and radiotherapy did not affect survival.
Impact of intestinal dysbiosis on breast cancer metastasis and progression
Authors: Zhang Jin , Xie Qiqi , Huo Xingfa , Liu Zhilin , Da Mengting , Yuan Mingxue , Zhao Yi , Shen Guoshuang
Published: November 2022

Breast cancer has a high mortality rate among malignant tumors, with metastases identified as the main cause of the high mortality. Dysbiosis of the gut microbiota has become a key factor in the development, treatment, and prognosis of breast cancer. The many microorganisms that make up the gut flora have a symbiotic relationship with their host and, through the regulation of host immune responses and metabolic pathways, are involved in important physiologic activities in the human body, posing a significant risk to health. In this review, we build on the interactions between breast tissue (including tumor tissue, tissue adjacent to the tumor, and samples from healthy women) and the microbiota, then explore factors associated with metastatic breast cancer and dysbiosis of the gut flora from multiple perspectives, including enterotoxigenic Bacteroides fragilis, antibiotic use, changes in gut microbial metabolites, changes in the balance of the probiotic environment and diet. These factors highlight the existence of a complex relationship between host-breast cancer progression-gut flora. Suggesting that gut flora dysbiosis may be a host-intrinsic factor affecting breast cancer metastasis and progression not only informs our understanding of the role of microbiota dysbiosis in breast cancer development and metastasis, but also the importance of balancing gut flora dysbiosis and clinical practice.
Treatment plan prescreening for patient-specific quality assurance measurements using independent Monte Carlo dose calculations
Authors: Xu Yuan , Zhang Ke , Liu Zhiqiang , Liang Bin , Ma Xiangyu , Ren Wenting , Men Kuo , Dai Jianrong
Published: November 2022

Purpose

This study proposes a method to identify plans that failed patient-specific quality assurance (QA) and attempts to establish a criterion to prescreen treatment plans for patient-specific QA measurements with independent Monte Carlo dose calculations.

Materials and methods

Patient-specific QA results measured with an ArcCHECK diode array of 207 patients (head and neck: 25; thorax: 61; abdomen: 121) were retrospectively analyzed. All patients were treated with the volumetric modulated arc therapy (VMAT) technique and plans were optimized with a Pinnacle v16.2 treatment planning system using an analytical algorithm-based dose engine. Afterwards, phantom verification plans were designed and recalculated by an independent GPU-accelerated Monte Carlo (MC) dose engine, ArcherQA. Moreover, sensitivity and specificity analyzes of gamma passing rates between measurements and MC calculations were carried out to show the ability of MC to monitor failing plans (ArcCHECK 3%/3 mm,<90%), and attempt to determine the appropriate threshold and gamma passing rate criterion utilized by ArcherQA to prescreen treatment plans for ArcCHECK measurements. The receiver operator characteristic (ROC) curve was also utilized to characterize the performance of different gamma passing rate criterion used by ArcherQA.

Results

The thresholds for 100% sensitivity to detect plans that failed patient-specific QA by independent calculation were 97.0%, 95.4%, and 91.0% for criterion 3%/3 mm, 3%/2 mm, and 2%/2 mm, respectively, which corresponded to specificities of 0.720, 0.528, and 0.585, respectively. It was shown that the 3%/3 mm criterion with 97% threshold for ArcherQA demonstrated perfect sensitivity and the highest specificity compared with other criteria, which may be suitable for prescreening treatment plans treated with the investigated machine to implement measurement-based patient-specific QA of patient plans. In addition, the area under the curve (AUC) calculated from ROC analysis for criterion 3%/3 mm, 3%/2 mm, and 2%/2 mm used by ArcherQA were 0.948, 0.924, and 0.929, respectively.

Conclusions

Independent dose calculation with the MC-based program ArcherQA has potential as a prescreen treatment for measurement-based patient-specific QA. AUC values (>0.9) showed excellent classification accuracy for monitoring failing plans with independent MC calculations.
Nomogram for prediction of peritoneal metastasis risk in colorectal cancer
Authors: Song Xian-qing , Liu Zhi-xian , Kong Qing-yuan , He Zhen-hua , Zhang Sen
Published: November 2022

Objective

Peritoneal metastasis is difficult to diagnose using traditional imaging techniques. The main aim of the current study was to develop and validate a nomogram for effectively predicting the risk of peritoneal metastasis in colorectal cancer (PMCC).

Methods

A retrospective case-control study was conducted using clinical data from 1284 patients with colorectal cancer who underwent surgery at the First Affiliated Hospital of Guangxi Medical University from January 2010 to December 2015. Least absolute shrinkage and selection operator (LASSO) regression was applied to optimize feature selection of the PMCC risk prediction model and multivariate logistic regression analysis conducted to determine independent risk factors. Using the combined features selected in the LASSO regression model, we constructed a nomogram model and evaluated its predictive value via receiver operating characteristic (ROC) curve analysis. The bootstrap method was employed for repeated sampling for internal verification and the discrimination ability of the prediction models evaluated based on the C-index. The consistency between the predicted and actual results was assessed with the aid of calibration curves.

Results

Overall, 96 cases of PMCC were confirmed via postoperative pathological diagnosis. Logistic regression analysis showed that age, tumor location, perimeter ratio, tumor size, pathological type, tumor invasion depth, CEA level, and gross tumor type were independent risk factors for PMCC. A nomogram composed of these eight factors was subsequently constructed. The calibration curve revealed good consistency between the predicted and actual probability, with a C-index of 0.882. The area under the curve (AUC) of the nomogram prediction model was 0.882 and its 95% confidence interval (CI) was 0.845–0.919. Internal validation yielded a C-index of 0.868.

Conclusion

We have successfully constructed a highly sensitive nomogram that should facilitate early diagnosis of PMCC, providing a robust platform for further optimization of clinical management strategies.