bluuebunny/crossref_metadata_2025 huggingface dataset:
NK Cells Under Hypoxia: The Two Faces of Vascularization in Tumor and Pregnancy
Authors: Garcés-Lázaro Irene , Kotzur Rebecca , Cerwenka Adelheid , Mandelboim Ofer
Published: June 2022

Environmental conditions greatly shape the phenotype and function of immune cells. Specifically, hypoxic conditions that exist within tissues and organs have been reported to affect both the adaptive and the innate immune system. Natural killer (NK) cells belong to the innate immune system. They are among the first immune cells responding to infections and are involved in tumor surveillance. NK cells produce cytokines that shape other innate and adaptive immune cells, and they produce cytolytic molecules leading to target cell killing. Therefore, they are not only involved in steady state tissue homeostasis, but also in pathogen and tumor clearance. Hence, understanding the role of NK cells in pathological and physiological immune biology is an emerging field. To date, it remains incompletely understood how the tissue microenvironment shapes NK cell phenotype and function. In particular, the impact of low oxygen concentrations in tissues on NK cell reactivity has not been systematically dissected. Here, we present a comprehensive review focusing on two highly compelling hypoxic tissue environments, the tumor microenvironment (pathological) and the decidua (physiological) and compare their impact on NK cell reactivity.
Juvenile Fish Associated With Pondweed and Charophyte Habitat in the Curonian Lagoon
Authors: Bučas Martynas , Lesutienė Jūratė , Nika Nerijus , Skersonas Andrius , Ivanauskas Edgaras , Srėbalienė Greta , Tiškus Edvinas , Gintauskas Jonas , Šaškov Aleksej , Martin Georg
Published: June 2022

Submerged macrophytes are essential elements of sublittoral ecosystems to maintain a diverse fish fauna. The aim of this study was to assess juvenile fish associated with macrophyte habitats in the Curonian Lagoon by means of modified pop net method. We focused on two dominant littoral habitats with different structure (pondweed and charophyte stands). The pop nets sampling was carried out on two study sites located in the freshwater and oligohaline part of the lagoon in July and September 2019-2020. Our upgraded pop nets reduced the risk of under sampling and are recommended for monitoring fishes since this method has relatively low disturbance on fish behavior and on the habitat itself. The most efficient time of sampling with pop nets in shallow macrophyte habitats is at night, where at least 4 samples collected are sufficient to represent the biggest part (> 70%) of the fish assemblage, but the sampling covering different times of day is recommended. In total, 14 juvenile species were recorded, where perch and European roach dominated (respectively 48% and 24%). Half of the species (8) were associated with macrophyte stands, although water salinity and temperature were the most important factors explaining the variance of fish abundance followed by the sampling time and the biomass of macrophytes. Based on the abundance and the duration of species within these habitats, European roach, nine-spined and three-spined stickleback were mainly associated with the pondweed biomass and stands, while spined loach, round goby, perch, ruffe and gudgeon were mainly associated with the charophyte biomass and stands. The increase of charophyte stands since 2005 affected the fish assemblage where it should have enhanced the abundance of perch, ruffe, spined loach and partly round goby.
Solamargine Alleviated UVB-Induced Inflammation and Melanogenesis in Human Keratinocytes and Melanocytes via the p38 MAPK Signaling Pathway, a Promising Agent for Post-inflammatory Hyperpigmentation
Authors: Zhao Juemin , Dan Yanjun , Liu Ziqi , Wang Qianqian , Jiang Min , Zhang Chengfeng , Sheu Hamm-Ming , Lin Chrang-Shi , Xiang Leihong
Published: June 2022

Post-inflammatory hyperpigmentation (PIH) is a common acquired pigmentary disorder occurring after skin inflammation or injury. Ultraviolet B irradiation could exaggerate PIH clinically due to its effect on promoting cutaneous inflammation and melanogenesis in keratinocytes and melanocytes, respectively. Solamargine (SM), a steroidal alkaloid glycoside extracted from Solanum undatum, significantly inhibits Ultraviolet B (UVB)-induced pro-inflammatory cytokines IL-1α, IL-1β, IL-8, and IFN-γ, as well as paracrine melanogenic factors ET-1, α-MSH, and bFGF in human keratinocytes. Additionally, SM significantly attenuated UVB-induced melanin synthesis in human epidermal melanocytes through down-regulation of tyrosinase activity and expression of MITF, TRP-1, TRP-2, and tyrosinase. SM exerted an anti-inflammatory effect in UVB-irradiated keratinocytes through the p38 MAPK/Nrf2/HO-1 signaling pathway. With its anti-inflammatory and whitening effect, SM may improve PIH through paracrine regulations of keratinocytes and direct action on melanocytes, making it a promising agent for PIH.
Recent Advances in Videolaryngoscopy for One-Lung Ventilation in Thoracic Anesthesia: A Narrative Review
Authors: Yao Wenlong , Li Meihong , Zhang Chuanhan , Luo Ailin
Published: June 2022

Since their advent, videolaryngoscopes have played an important role in various types of airway management. Lung isolation techniques are often required for thoracic surgery to achieve one-lung ventilation with a double-lumen tube (DLT) or bronchial blocker (BB). In the case of difficult airways, one-lung ventilation is extremely challenging. The purpose of this review is to identify the roles of videolaryngoscopes in thoracic airway management, including normal and difficult airways. Extensive literature related to videolaryngoscopy and one-lung ventilation was analyzed. We summarized videolaryngoscope-guided DLT intubation techniques and discussed the roles of videolaryngoscopy in DLT intubation in normal airways by comparison with direct laryngoscopy. The different types of videolaryngoscopes for DLT intubation are also compared. In addition, we highlighted several strategies to achieve one-lung ventilation in difficult airways using videolaryngoscopes. A non-channeled or channeled videolaryngoscope is suitable for DLT intubation. It can improve glottis exposure and increase the success rate at the first attempt, but it has no advantage in saving intubation time and increases the incidence of DLT mispositioning. Thus, it is not considered as the first choice for patients with anticipated normal airways. Current evidence did not indicate the superiority of any videolaryngoscope to another for DLT intubation. The choice of videolaryngoscope is based on individual experience, preference, and availability. For patients with difficult airways, videolaryngoscope-guided DLT intubation is a primary and effective method. In case of failure, videolaryngoscope-guided single-lumen tube (SLT) intubation can often be achieved or combined with the aid of fibreoptic bronchoscopy. Placement of a DLT over an airway exchange catheter, inserting a BB via an SLT, or capnothorax can be selected for lung isolation.
Blood Flow Restriction Training for the Intervention of Sarcopenia: Current Stage and Future Perspective
Authors: Zhang Xu-zhi , Xie Wen-qing , Chen Lin , Xu Guo-dong , Wu Li , Li Yu-sheng , Wu Yu-xiang
Published: June 2022

Sarcopenia is a geriatric syndrome that is characterized by a progressive and generalized skeletal muscle disorder and can be associated with many comorbidities, including obesity, diabetes, and fracture. Its definitions, given by the AWGS and EWGSOP, are widely used. Sarcopenia is measured by muscle strength, muscle quantity or mass and physical performance. Currently, the importance and urgency of sarcopenia have grown. The application of blood flow restriction (BFR) training has received increased attention in managing sarcopenia. BFR is accomplished using a pneumatic cuff on the proximal aspect of the exercising limb. Two main methods of exercise, aerobic exercise and resistance exercise, have been applied with BFR in treating sarcopenia. Both methods can increase muscle mass and muscle strength to a certain extent. Intricate mechanisms are involved during BFRT. Currently, the presented mechanisms mainly include responses in the blood vessels and related hormones, such as growth factors, tissue hypoxia-related factors and recruitment of muscle fiber as well as muscle satellite cells. These mechanisms contribute to the positive balance of skeletal muscle synthesis, which in turn mitigates sarcopenia. As a more suited and more effective way of treating sarcopenia and its comorbidities, BFRT can serve as an alternative to traditional exercise for people who have marked physical limitations or even show superior outcomes under low loads. However, the possibility of causing stress or muscle damage must be considered. Cuff size, pressure, training load and other variables can affect the outcome of sarcopenia, which must also be considered. Thoroughly studying these factors can help to better determine an ideal BFRT scheme and better manage sarcopenia and its associated comorbidities. As a well-tolerated and novel form of exercise, BFRT offers more potential in treating sarcopenia and involves deeper insights into the function and regulation of skeletal muscle.
High Prevalence of Mycoplasma penetrans in Chlamydia trachomatis Positive Rectal Samples From Men: A Brief Report
Authors: Pérez-Prieto Inmaculada , Skafte-Holm Axel , Jensen Jørgen Skov
Published: June 2022

Mycoplasma penetrans has gained increased attention in relation to sexually transmitted infections, however, its pathogenic potential and prevalence in different populations remains to be elucidated. Among 293 Chlamydia trachomatis positive rectal samples submitted for lymphogranuloma venereum typing, M. penetrans was detected by PCR in 13.4% of 231 male samples.
Collective Variable for Metadynamics Derived From AlphaFold Output
Authors: Spiwok Vojtěch , Kurečka Martin , Křenek Aleš
Published: June 2022

AlphaFold is a neural network–based tool for the prediction of 3D structures of proteins. In CASP14, a blind structure prediction challenge, it performed significantly better than other competitors, making it the best available structure prediction tool. One of the outputs of AlphaFold is the probability profile of residue–residue distances. This makes it possible to score any conformation of the studied protein to express its compliance with the AlphaFold model. Here, we show how this score can be used to drive protein folding simulation by metadynamics and parallel tempering metadynamics. Using parallel tempering metadynamics, we simulated the folding of a mini-protein Trp-cage and β hairpin and predicted their folding equilibria. We observe the potential of the AlphaFold-based collective variable in applications beyond structure prediction, such as in structure refinement or prediction of the outcome of a mutation.
Meta-Analysis of Down Syndrome Cortical Development Reveals Underdeveloped State of the Science
Authors: Risgaard Kirstin A. , Sorci Isabella A. , Mohan Sruti , Bhattacharyya Anita
Published: June 2022

Neurodevelopmental impairment contributes to the hallmark cognitive disability in individuals with Down syndrome (DS, trisomy 21, T21). The appearance of cognitive deficits in infancy suggests that alterations emerge during the earliest stages of neural development and continue throughout the lifespan in DS. Neural correlates of intellectual and language function include cortical structures, specifically temporal and frontal lobes that are smaller in DS. Yet, despite increased understanding of the DS cognitive-behavioral phenotype in childhood, there is very little structural and histological information to help explain the deficits. Consequently, attempts to effectively design therapeutic targets or interventions are limited. We present a systematic review of published research on cortical development in DS that reveals a paucity of studies that rigorously identify cellular features that may underlie the gross morphological deficits of the developing DS brain. We assessed 115 published reports retrieved through PubMed and other sources and found that only 23 reported histological and/or immunohistochemical data to define cell composition affected in DS post-mortem brain. Further, our analysis reveals that many reports have limited samples sizes and few DS samples, making it difficult to draw conclusions that are generally applicable to the DS population. Thus, the lack of replication and limited number of studies indicate that more developmentally focused research, ideally using equal numbers of age-matched samples in analyses, is needed to elucidate the cellular nature of smaller brain size in DS.
The Relevance of Collision Tests and Quantitative Sensory Testing in Diagnostics and Postoperative Outcome Prediction in Carpal Tunnel Syndrome
Authors: Koszewicz Magdalena , Szydlo Mariusz , Gosk Jerzy , Wieczorek Malgorzata , Slotwinski Krzysztof , Budrewicz Slawomir
Published: June 2022

Background

The gold standards for the diagnosis and treatment of carpal tunnel syndrome (CTS) and its outcome are undecided. Using clinical and electrophysiological methods, we tried to establish which fibers achieved full postoperative recovery, and the possibility of using non-standard electrophysiological tests as outcome predictors.

Methods

The study group consisted of 35 patients and controls. The Historical–Objective Scale, standard neurography, conduction velocity distribution tests (CVD), and quantitative sensory testing (QST) were performed before and after CTS surgery.

Results

Clinical improvement was observed on average in 54.3% of the patients, higher in less advanced CTS. All parameters improved significantly after surgery, except for CVD; most remained worse than in the controls. Only QST parameters fully returned to normal limits. Patient age and CTS severity were important in the estimation of the risk of no improvement.

Conclusions

The efficiency of minimally invasive CTS surgery is higher in younger patients with less advanced CTS. Complete recovery was present only in small fibers; larger fibers could most likely be responsible for residual signs. We did not notice any benefits in CTS diagnosis using methods of small fiber assessment. QST seemed to be useful in the diagnosis of residual signs, and in deciding upon possible reoperation.
Prognostic Value of Serum Albumin Level in Critically Ill Patients: Observational Data From Large Intensive Care Unit Databases
Authors: Jin Xuting , Li Jiamei , Sun Lu , Zhang Jingjing , Gao Ya , Li Ruohan , Ren Jiajia , Hou Yanli , Su Dan , Liu Jiao , Wang Xiaochuang , Chen Dechang , Wang Gang , Wiedermann Christian J.
Published: June 2022

Background

Decreased serum albumin level (SAL) is associated with adverse clinical outcomes. We designed the present study to further assess the prognostic value of SAL in critically ill patients based on data from large intensive care unit (ICU) databases.

Methods

This retrospective cohort study recruited 18,353 patients from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Restricted cubic splines (RCS) were performed to visualize the association of SAL at admission with ICU and hospital mortalities. The prognostic value of SAL was analyzed using logistic regression models and receiver operating characteristic (ROC) curves in overall patients and subgroups.

Results

Restricted cubic splines revealed rapid increasing risks in ICU and hospital mortalities when SAL declined to below 30 g/l. Patients with SAL <30 g/l (n = 6,069) had higher ICU (13.7% vs. 6.4%, p < 0.001) and hospital (23.9% vs. 10.7%, p < 0.001) mortalities than those with SAL ≥30 g/l. Multivariable logistic regression model revealed that SAL <30 g/l independently correlated with higher risks of both ICU (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07–1.36) and hospital (OR: 1.51, 95% CI: 1.37–1.66) mortalities. However, the association diminished in patients with cirrhosis (OR: 1.16, 95% CI: 0.91–1.49 for ICU mortality; OR: 1.21, 95% CI: 1.00–1.48 for hospital mortality). ROC curves revealed a poor performance of SAL in predicting mortalities, both in overall patients and in those with cirrhosis.

Conclusions

Decreased SAL is associated with increased risk of mortality. However, it possesses low sensitivity and specificity for outcome prediction in critically ill patients, especially in those with cirrhosis.
Mogroside-Rich Extract From Siraitia grosvenorii Fruits Ameliorates High-Fat Diet-Induced Obesity Associated With the Modulation of Gut Microbiota in Mice
Authors: Wang Siyuan , Cui Kexin , Liu Jiahao , Hu Jiahao , Yan Ke , Xiao Peng , Lu Yangqing , Yang Xiaogan , Liang Xingwei
Published: June 2022

Siraitia grosvenorii is a kind of medicinal food plant. The mogroside-rich extract (MGE) of its fruits can effectively ameliorate obesity, but the underlying mechanisms remain underexplored. In this study, we aimed to determine whether MGE can ameliorate obesity by protecting against the divergences of gut microbiota. Mice were challenged with a high-fat diet (HFD) and treated with MGE by oral gavage. Then, the characteristics of the gut microbiota were determined by 16S rDNA analysis. Our findings showed that MGE could significantly reduce body weight gain and fat tissue weight of the mice fed with HFD. Moreover, MGE markedly attenuated fatty liver, and improved glucose tolerance and insulin sensitivity. We further found that the gut microbiota structures were disturbed by HFD feeding. In particular, the abundance of Firmicutes was increased and the abundance of Bacteroidetes was decreased, resulting in an increased proportion of Firmicutes to Bacteroidetes (F/B), which contributes to obesity. Interestingly, the abnormal proportion of F/B of HFD feeding mice was restored to the level of control mice by MGE treatment. Additionally, the abundances of obesogenic microbiota, such as Ruminiclostridium and Oscillibacter were also decreased after MGE treatment. In summary, our findings demonstrate that MGE can modulate gut microbiota in obese mice and shed new light on how it alleviates obesity.
Assessing Variability in Vascular Response to Cocoa With Personal Devices: A Series of Double-Blind Randomized Crossover n-of-1 Trials
Authors: Bapir Mariam , Campagnolo Paola , Rodriguez-Mateos Ana , Skene Simon S. , Heiss Christian
Published: June 2022

Controlled clinical intervention studies have demonstrated that cocoa flavanols (CF) can decrease blood pressure and arterial stiffness in healthy humans, although a large variability in the effect size across trials has been reported. In this study, we evaluated the intra- and inter-individual variability of responses to CF in everyday life using a series of n-of-1 trials in healthy free-living individuals with normal blood pressure carrying personal devices. In total, eleven healthy young humans participated in a repeated crossover randomized controlled double-blind n-of-1 trial. On 8 consecutive days, each volunteer consumed on alternating days 6 CF capsules (862 mg CF) on 4 days and 6 matched placebo capsules (P, 0 mg CF/day) on another 4 days in one of the two randomized sequences (CF-P-CF-P-CF-P-CF-P or P-CF-P-CF-P-CF-P-CF). On each day, the capsules were taken at the same time in the morning with breakfast after baseline measurements. Each subject was provided with an upper arm blood pressure monitor and a finger clip that measures pulse wave velocity (PWV). Measurements of blood pressure, heart rate, and PWV were taken at least hourly over 12 h during the day by the participants. On the first 2 days, measurements were performed under supervision to provide training. The overall mixed model analysis showed that CF significantly decreased 12-h systolic blood pressure and PWV by −1.4 ± 0.3 mmHg and −0.11 ± 0.03 m/s, respectively. Peak effects were observed within the first 3 h (1.5 h SBP: −4.9 ± 2.2 mmHg, PWV: −0.32 ± 0.17 m/s) and again after 8 h post-ingestion. Large inter-individual variation in responses was found [intra-cluster correlation coefficients (ICC): 0.41, 0.41]. When analyzing single individuals’ datasets, there was also considerable between-day variation in individual responses that varied greatly between subjects (ICC: 0–0.30, 0–0.22, 0–0.45). Effect sizes inversely correlated with baseline blood pressure values both between- and within-subjects. The data confirm that cocoa can decrease blood pressure and arterial stiffness in everyday life when elevated within the normal range. The large inter- and intra-individual variation in responses calls for more personalized nutritional intervention strategies.
The Specifically Androgen-Regulated Gene (SARG) Promotes Papillary Thyroid Carcinoma (PTC) Lymphatic Metastasis Through Vascular Endothelial Growth Factor C (VEGF-C) and VEGF Receptor 3 (VEGFR-3) Axis
Authors: Xu Shuai-Jun , Jin Bin , Zhao Wei-Jun , Chen Xue-Xian , Tong Ying-Ying , Ding Xiao-Fei , Chen Ying-Yuan , Wang Dong-Hao , Wang Zhi-Ming , Dai Bing-Qing , Chen Sai , Liang Yong , Chen Guang , Pan Su-Jiao , Xu Ling-Long
Published: June 2022

The papillary thyroid carcinoma (PTC) metastasizes through lymphatic spread, but the follicular thyroid cancer (FTC) metastasis occurs by following hematogenous spread. To date, the molecular mechanism underlying different metastatic routes between PTC and FTC is still unclear. Here, we showed that specifically androgen-regulated gene (SARG) was significantly up-regulated in PTC, while obviously down-regulated in FTC through analyzing the Gene Expression Omnibus (GEO) database. Immunohistochemistry assay verified that the PTC lymph node metastasis was associated with higher levels of SARG protein in clinical PTC patient samples. SARG-knockdown decreased TPC-1 and CGTH-W3 cells viability and migration significantly. On the contrary, SARG-overexpressed PTC cells possessed more aggressive migratory ability and viability. In vivo, SARG overexpression dramatically promoted popliteal lymph node metastasis of xenografts from TPC-1 cells mouse footpad transplanting. Mechanistically, SARG overexpression and knockdown significantly increased and decreased the expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3), respectively, thereby facilitating or inhibiting the tube formation in HUVECs. The tube formation experiment showed that SARG overexpression and knockdown promoted or inhibited the number of tube formations in HUVEC cells, respectively. Taken together, we showed for the first time the differential expression profile of SARG between PTC and FTC, and SARG promotes PTC lymphatic metastasis via VEGF-C/VEGFR-3 signal. It indicates that SARG may represent a target for clinical intervention in lymphatic metastasis of PTC.
Increased Expression of Mitochondrial UQCRC1 in Pancreatic Cancer Impairs Antitumor Immunity of Natural Killer Cells via Elevating Extracellular ATP
Authors: Cong Hui , Gao Jian , Wang Qing , Du Min , Li Huimin , Li Qian , Li Jin , Liang Yiyi , Zhao Dan , Yang Hancao , Gan Yu , Tu Hong
Published: June 2022

Pancreatic cancer (PC) is one of the most lethal malignancies characterized by a highly immunosuppressive tumor microenvironment (TME). Previously, we have reported that ubiquinol-cytochrome c reductase core protein I (UQCRC1), a key component of mitochondrial complex III, is generally upregulated in PC and produces extracellular ATP (eATP) to promote PC progression. Here, we sought to investigate whether the oncogenic property of UQCRC1 is generated through its effects on natural killer (NK) cells in the TME. We found that UQCRC1 overexpression in PC cells inhibited cytotoxicity of NK cells, as well as the infiltration of NK cells toward PC, whereas knockdown of UQCRC1 enhanced the cytotoxicity and chemotaxis of NK cells. Adoptive NK cell therapy in the subcutaneous mouse model and CIBERSORTx analysis with human PC specimens confirmed UQCRC1 elicited immunosuppressive effects on NK cells. Such UQCRC1-induced impairment of NK cells was mediated by eATP and its metabolite adenosineviaP2Y11R and A2AR, respectively. Mechanistically, we found the UQCRC1/eATP axis reduced the expression of chemokine CCL5 in cancer cells and altered the balance of activating receptor DNAM-1 and inhibitory receptor CD96 on NK-92MI cells, resulting in decreased chemotaxis and exhausted phenotype of NK-92MI cells. Taken together, our study provides the evidence to support a novel mechanism by which energy metabolism change in cancer cells remodels the TME and impedes NK cell surveillance. It also suggests that targeting UQCRC1 may be a potential combined strategy for PC immunotherapy.
Immune Activation, Exhaustion and Senescence Profiles as Possible Predictors of Cancer in Liver Transplanted Patients
Authors: Petrara Maria Raffaella , Shalaby Sarah , Ruffoni Elena , Taborelli Martina , Carmona Francesco , Giunco Silvia , Del Bianco Paola , Piselli Pierluca , Serraino Diego , Cillo Umberto , Dolcetti Riccardo , Burra Patrizia , De Rossi Anita
Published: June 2022

Liver transplanted (LT) patients for hepatocellular carcinoma (LT-HCC) or for other causes (LT-no-HCC) may develop post-transplantation malignancies. Although immune activation and senescence are frequently implicated in cancer development, no data is available on their possible role as biomarkers predictive of tumor onset in this setting. A total of 116 patients were investigated: the 45 LT-HCC patients were older than the 71 LT-non-HCC (p=0.011), but comparable for sex, HCV, HBV infection and immunosuppressive treatment. At baseline, the numbers of activated and senescent-like circulating cells were significantly higher in LT-HCC patients than in LT-no-HCC ones. After a median follow-up of 26.8 months, 6 post-transplant malignancies (PTM) occurred: 4 in LT-HCC (8.9%) and 2 in LT-no-HCC (2.8%) patients. Overall, subjects with high percentages of activated and exhausted T and B cells at baseline were at higher risk of PTM. Notably, within the LT-HCC group, a higher percentage of senescence-like T cells was also associated with cancer development. Moreover, patients with PTM had higher telomere erosion and higher levels of circulating PAMPs (16S rDNA) and DAMPs (mtDNA) when compared with matched patients without PTM. Overall, these findings suggest that immune activation and exhaustion may be useful to predict the risk of PTM occurrence, regardless of the cause of transplantation. In LT-HCC, T-cell senescence represents an additional risk factor for tumor onset.
Development and Validation of the Breast Cancer Scale QLICP-BR V2.0 Based on Classical Test Theory and Generalizability Theory
Authors: Li Fei , Zhou Jiali , Wan Chonghua , Yang Zheng , Liang Qilian , Li Weiqiang , Chen Huanwei
Published: June 2022

Objective

The aim of this study was to develop and validate the breast cancer scale among the system of quality-of-life instruments for cancer patients (QLICP-BR V2.0).

Methods

Programmed decision procedures and theories on instrument development were applied to develop QLICP-BR V2.0. A total of 246 breast cancer inpatients were investigated using QLICP-BR V2.0 from hospital admission until discharge. The reliability, validity, and responsiveness of the QLICP-BR V2.0 scale were evaluated by using the classical test theory combined with the generalizability theory (GT), including correlation analysis, multi-trait scaling analysis, factor analyses, t-tests, and also multivariate generalizability theory analysis.

Results

The test–retest reliability of the total scale is 0.79, the Cronbach coefficient is 0.85, and the intra-class correlations coefficient is 0.88. The item–domain correlation analysis showed that the correlation coefficient between items and their own domain is greater than that with other domains except of item GSO4. The exploratory factor analysis showed that three principal components are obtained in the specific module. The outcome of the factor analysis coincides substantially with our theoretical conception. The score difference of each domain of the scale and the total scale before and after treatment is statistically significant (P < 0.05), with the standardized response mean of the total scale being 0.61. According to GT, the generalization coefficient of the scores in the 5 domains is between 0.626 and 0.768, and the reliability index is between 0.557 and 0.695.

Conclusion

QLICP-BR V2.0 exhibited reasonable degrees of validity, reliability, and responsiveness according to classical test and the generalizability theory. The number of items in the scale is appropriate.
Roles of Autotaxin/Autotaxin-Lysophosphatidic Acid Axis in the Initiation and Progression of Liver Cancer
Authors: She Sha , Zhang Qian , Shi Jinzhi , Yang Fan , Dai Kai
Published: June 2022

Autotaxin (ATX) is a secreted glycoprotein and catalyzes the hydrolysis of lysophosphatidylcholine to lysophosphatidic acid (LPA), a growth factor-like signaling phospholipid. ATX has been abundantly detected in the culture medium of various cancer cells, tumor tissues, and serum or plasma of cancer patients. Biological actions of ATX are mediated by LPA. The ATX-LPA axis mediates a plethora of activities, such as cell proliferation, survival, migration, angiogenesis, and inflammation, and participates in the regulation of various physiological and pathological processes. In this review, we have summarized the physiological function of ATX and the ATX-LPA axis in liver cancer, analyzed the role of the ATX-LPA axis in tumorigenesis and metastasis, and discussed the therapeutic strategies targeting the ATX-LPA axis, paving the way for new therapeutic developments.
Dacomitinib for Advanced Non-small Cell Lung Cancer Patients Harboring Major Uncommon EGFR Alterations: A Dual-Center, Single-Arm, Ambispective Cohort Study in China
Authors: Li Hong-Shuai , Yang Guang-Jian , Cai Yi , Li Jun-Ling , Xu Hai-Yan , Zhang Tao , Zhou Li-Qiang , Wang Yu-Ying , Wang Jin-Liang , Hu Xing-Sheng , Yan Xiang , Wang Yan
Published: June 2022

Objective: Dacomitinib has been approved for non-small-cell lung cancer (NSCLC) patients harboring classical epidermal growth factor receptor (EGFR) mutations; however, clinical evidence of its activity on major uncommon EGFR mutations is currently limited.

Materials and methods: This was a dual-center, single-arm, ambispective cohort study in China. Patients with histologically confirmed metastatic or recurrent NSCLC harboring major uncommon EGFR mutations were eligible for the study. The objective response rate and disease control rate were determined by RECIST 1.1 every 1–2 months. Adverse events were assessed by CTCAE 5.0.

Results: In total, 32 NSCLC patients were enrolled between July 2020 and January 2022, and 18 (56.3%) patients received dacomitinib as first-line therapy. Median age was 64 years, and 20 (62.5%) were female. The mutations identified were G719X (n = 24; 75%), followed by L861X (n = 10; 31.3%), and S768I (n = 8; 25%). In the first-line setting, 72.2% of patients (13/18) had a confirmed partial response and 100% (18/18) had disease control, and the median progression-free survival (PFS) and overall survival (OS) were unreached. In the whole cohort, 56.3% of patients (18/32) had a confirmed partial response and 90.6% (29/32) had disease control, and the median PFS was 10.3 months (95% confidence interval, 6.1–14.5) and the median OS was 36.5 months. Except for one case not available for brain re-evaluation, control of the intracranial metastases was observed in 13 patients (13/14, 92.9%). No grade 4–5 adverse events (AEs) occurred, but all patients had grade 1–2 AEs, and 12.5% (4/32) patients required a dosage reduction due to intolerable AEs.

Conclusions: Dacomitinib demonstrated favorable activity with manageable toxicity in patients with NSCLC harboring major uncommon EGFR mutations.
Advances in Research on the Effects and Mechanisms of Chemokines and Their Receptors in Cancer
Authors: Xu Jing , Li Jing-quan , Chen Qi-lei , Shestakova Elena A. , Misyurin Vsevolod A. , Pokrovsky Vadim S. , Tchevkina Elena M. , Chen Hu-biao , Song Hang , Zhang Jian-ye
Published: June 2022

Cancer is a common and intractable disease that seriously affects quality of life of patients and imposes heavy economic burden on families and the entire society. Current medications and intervention strategies for cancer have respective shortcomings. In recent years, it has been increasingly spotlighted that chemokines and their receptors play vital roles in the pathophysiology of cancer. Chemokines are a class of structurally similar short-chain secreted proteins that initiate intracellular signaling pathways through the activation of corresponding G protein-coupled receptors and participate in physiological and pathological processes such as cell migration and proliferation. Studies have shown that chemokines and their receptors have close relationships with cancer epigenetic regulation, growth, progression, invasion, metastasis, and angiogenesis. Chemokines and their receptors may also serve as potential targets for cancer treatment. We herein summarize recent research progresses on anti-tumor effects and mechanisms of chemokines and their receptors, suggesting avenues for future studies. Perspectives for upcoming explorations, such as development of multi-targeted chemokine-based anti-tumor drugs, are also discussed in the present review.
Nematic Fluctuations in the Non-Superconducting Iron Pnictide BaFe1.9−xNi0.1CrxAs2
Authors: Gong Dongliang , Yi Ming , Wang Meng , Xie Tao , Zhang Wenliang , Danilkin Sergey , Deng Guochu , Liu Xinzhi , Park Jitae T. , Ikeuchi Kazuhiko , Kamazawa Kazuya , Mo Sung-Kwan , Hashimoto Makoto , Lu Donghui , Zhang Rui , Dai Pengcheng , Birgeneau Robert J. , Li Shiliang , Luo Huiqian
Published: June 2022

The main driven force of the electronic nematic phase in iron-based superconductors is still under debate. Here, we report a comprehensive study on the nematic fluctuations in a non-superconducting iron pnictide system BaFe1.9−xNi0.1CrxAs2 by electronic transport, angle-resolved photoemission spectroscopy (ARPES), and inelastic neutron scattering (INS) measurements. Previous neutron diffraction and transport measurements suggested that the collinear antiferromagnetism persists to x = 0.8, with similar Néel temperature TN and structural transition temperature Ts around 32 K, but the charge carriers change from electron type to hole type around x = 0.5. In this study, we have found that the in-plane resistivity anisotropy also highly depends on the Cr dopings and the type of charge carriers. While ARPES measurements suggest possibly weak orbital anisotropy onset near Ts for both x = 0.05 and x = 0.5 compounds, INS experiments reveal clearly different onset temperatures of low-energy spin excitation anisotropy, which is likely related to the energy scale of spin nematicity. These results suggest that the interplay between the local spins on Fe atoms and the itinerant electrons on Fermi surfaces is crucial to the nematic fluctuations of iron pnictides, where the orbital degree of freedom may behave differently from the spin degree of freedom, and the transport properties are intimately related to the spin dynamics.
Performing Bayesian Analyses With AZURE2 Using BRICK: An Application to the 7Be System
Authors: Odell Daniel , Brune Carl R. , Phillips Daniel R. , deBoer Richard James , Paneru Som Nath
Published: June 2022

Phenomenological R-matrix has been a standard framework for the evaluation of resolved resonance cross section data in nuclear physics for many years. It is a powerful method for comparing different types of experimental nuclear data and combining the results of many different experimental measurements in order to gain a better estimation of the true underlying cross sections. Yet a practical challenge has always been the estimation of the uncertainty on both the cross sections at the energies of interest and the fit parameters, which can take the form of standard level parameters. Frequentist (χ2-based) estimation has been the norm. In this work, a Markov Chain Monte Carlo sampler, emcee, has been implemented for the R-matrix code AZURE2, creating the Bayesian R-matrix Inference Code Kit (BRICK). Bayesian uncertainty estimation has then been carried out for a simultaneous R-matrix fit of the 3He (α,γ)7Be and 3He (α,α)3He reactions in order to gain further insight into the fitting of capture and scattering data. Both data sets constrain the values of the bound state α-particle asymptotic normalization coefficients in 7Be. The analysis highlights the need for low-energy scattering data with well-documented uncertainty information and shows how misleading results can be obtained in its absence.
MEMS Modulator-Based Mid-Infrared Laser Heterodyne Radiometer for Atmospheric Remote Sensing
Authors: Xue Zhengyue , Shen Fengjiao , Li Jun , Liu Xiaohai , Wang Guishi , Liu Kun , Gao Xiaoming , Chen Weidong , Tan Tu
Published: June 2022

The performance of a mid-infrared laser heterodyne radiometer (MIR-LHR) based on a micro-electro-mechanical system (MEMS) mirror is demonstrated in ground-based solar occultation mode. A MEMS mirror is employed as an alternative modulator to the traditional mechanical chopper. High-resolution (∼0.0024 cm−1) transmission spectrum near 3.93 μm was obtained for atmospheric observation of N2O absorption. Operation of the MIR-LHR with laser-induced shot-noise limited performance was analyzed and experimentally achieved. The laser heterodyne spectrum obtained is consistent with Fourier-transform infrared (FT-IR) spectrometer and atmospheric transmission modeling. Compared to the traditional chopper, the MEMS mirror is smaller, lighter and lower power consumption which makes the system more stable and compact. The reported MIR-LHR in this article has great potential in aircraft instruments and satellite payloads.
Passive Exoskeleton-Assisted Gait Shows a Unique Interlimb Coordination Signature Without Restricting Regular Walking
Authors: Sado Takashi , Motz Zachary , Yentes Jennifer M. , Mukherjee Mukul
Published: June 2022

Exoskeleton assistive devices have been developed as a potential approach to solve gait deficits like paretic propulsion and reduced speed. However, it is unclear how these devices affect inter-limb coordination. The duration and the synchrony of gait coordination was assessed during passive exoskeleton-assisted walking in healthy young individuals. It was hypothesized that inter-limb coordination would be reduced in comparison to normal walking without assistance, thus demonstrating gait with exoskeleton to be more explorative and flexible. Eighteen participants were divided into two groups (EXO: n = 9; NO EXO: n = 9) and performed a 5-min walking trial at a preferred walking speed after a familiarization trial. The duration of inter-limb coordination was examined using cross-recurrence quantification analysis and the synchrony was measured using cross sample entropy. There were no significant differences in spatiotemporal measurements between the two groups. However, in comparison to the no exoskeleton group, there was a reduction in the duration of coordination (mean diagonal length: p < 0.01) and the synchrony of coordination (entropy value: p < 0.05) in the exoskeleton group. These results indicate that exoskeletal-assisted gait is characterized by reduced inter-limb coordination possibly for allowing gait patterns to be more explorative and flexible. This is important in rehabilitation of patients who suffer from coordination deficits.
Reliable DNA Markers for a Previously Unidentified, Yet Broadly Deployed Hessian Fly Resistance Gene on Chromosome 6B in Pacific Northwest Spring Wheat Varieties
Authors: Prather Samuel , Schneider Tavin , Gaham Godoy Jayfred , Odubiyi Steven , Bosque-Perez Nilsa A. , Rashed Arash , Rynearson Sheri , Pumphrey Michael O.
Published: June 2022

Hessian fly [Mayetiola destructor (Say)] is a major pest of wheat (Triticum aestivum L.) throughout the United States and in several other countries. A highly effective and economically feasible way to control Hessian fly is with resistant cultivars. To date, over 37 Hessian fly resistance genes have been discovered and their approximate locations mapped. Resistance breeding is still limited, though, by the genes’ effectiveness against predominant Hessian fly biotypes in a given production area, genetic markers that are developed for low-throughput marker systems, poorly adapted donor germplasm, and/or the inadequacy of closely linked DNA markers to track effective resistance genes in diverse genetic backgrounds. The purposes of this study were to determine the location of the Hessian fly resistance gene in the cultivar “Kelse” (PI 653842) and to develop and validate Kompetitive Allele Specific PCR (KASP) markers for the resistance locus. A mapping population was genotyped and screened for Hessian fly resistance. The resulting linkage map created from 2,089 Single Nucleotide Polymorphism SNP markers placed the resistance locus on the chromosome 6B short arm, near where H34 has been reported. Three flanking SNPs near the resistance locus were converted to KASP assays which were then validated by fine-mapping and testing a large panel of breeding lines from hard and soft wheat germplasm adapted to the Pacific Northwest. The KASP markers presented here are tightly linked to the resistance locus and can be used for marker-assisted selection by breeders working on Hessian fly resistance and allow confirmation of this Hessian fly resistance gene in diverse germplasm.
Phenotypic Variation and the Impact of Admixture in the Oryza rufipogon Species Complex (ORSC)
Authors: Eizenga Georgia C. , Kim HyunJung , Jung Janelle K. H. , Greenberg Anthony J. , Edwards Jeremy D. , Naredo Maria Elizabeth B. , Banaticla-Hilario Maria Celeste N. , Harrington Sandra E. , Shi Yuxin , Kimball Jennifer A. , Harper Lisa A. , McNally Kenneth L. , McCouch Susan R.
Published: June 2022

Crop wild relatives represent valuable reservoirs of variation for breeding, but their populations are threatened in natural habitats, are sparsely represented in genebanks, and most are poorly characterized. The focus of this study is the Oryza rufipogon species complex (ORSC), wild progenitor of Asian rice (Oryza sativa L.). The ORSC comprises perennial, annual and intermediate forms which were historically designated as O. rufipogon, O. nivara, and O. sativa f. spontanea (or Oryza spp., an annual form of mixed O. rufipogon/O. nivara and O. sativa ancestry), respectively, based on non-standardized morphological, geographical, and/or ecologically-based species definitions and boundaries. Here, a collection of 240 diverse ORSC accessions, characterized by genotyping-by-sequencing (113,739 SNPs), was phenotyped for 44 traits associated with plant, panicle, and seed morphology in the screenhouse at the International Rice Research Institute, Philippines. These traits included heritable phenotypes often recorded as characterization data by genebanks. Over 100 of these ORSC accessions were also phenotyped in the greenhouse for 18 traits in Stuttgart, Arkansas, and 16 traits in Ithaca, New York, United States. We implemented a Bayesian Gaussian mixture model to infer accession groups from a subset of these phenotypic data and ascertained three phenotype-based group assignments. We used concordance between the genotypic subpopulations and these phenotype-based groups to identify a suite of phenotypic traits that could reliably differentiate the ORSC populations, whether measured in tropical or temperate regions. The traits provide insight into plant morphology, life history (perenniality versus annuality) and mating habit (self- versus cross-pollinated), and are largely consistent with genebank species designations. One phenotypic group contains predominantly O. rufipogon accessions characterized as perennial and largely out-crossing and one contains predominantly O. nivara accessions characterized as annual and largely inbreeding. From these groups, 42 “core” O. rufipogon and 25 “core” O. nivara accessions were identified for domestication studies. The third group, comprising 20% of our collection, has the most accessions identified as Oryza spp. (51.2%) and levels of O. sativa admixture accounting for more than 50% of the genome. This third group is potentially useful as a “pre-breeding” pool for breeders attempting to incorporate novel variation into elite breeding lines.
Variation in Grain Zinc and Iron Concentrations, Grain Yield and Associated Traits of Biofortified Bread Wheat Genotypes in Nepal
Authors: Thapa Dhruba Bahadur , Subedi Mahesh , Yadav Rajendra Prasad , Joshi Bishnu Prasad , Adhikari Bhim Nath , Shrestha Keshav Prasad , Magar Prem Bahadur , Pant Khem Raj , Gurung Suk Bahadur , Ghimire Sapana , Gautam Nutan Raj , Acharya Nav Raj , Sapkota Manoj , Mishra Vinod Kumar , Joshi Arun Kumar , Singh Ravi Prakash , Govindan Velu
Published: June 2022

Wheat (Triticum aestivum L.) is one of the major staples in Nepal providing the bulk of food calories and at least 30% of Fe and Zn intake and 20% of dietary energy and protein consumption; thus, it is essential to improve its nutritional quality. To select high-yielding genotypes with elevated grain zinc and iron concentration, the sixth, seventh, eighth, and ninth HarvestPlus Yield Trials (HPYTs) were conducted across diverse locations in Nepal for four consecutive years: 2015–16, 2016–17, 2017–18, and 2018–19, using 47 biofortified and 3 non-biofortified CIMMYT-bred, bread wheat genotypes: Baj#1, Kachu#1, and WK1204 (local check). Genotypic and spatial variations were found in agro-morphological traits; grain yield and its components; and the grain zinc and iron concentration of tested genotypes. Grain zinc concentration was highest in Khumaltar and lowest in Kabre. Likewise, grain iron concentration was highest in Doti and lowest in Surkhet. Most of the biofortified genotypes were superior for grain yield and for grain zinc and iron concentration to the non-biofortified checks. Combined analyses across environments showed moderate to high heritability for both Zn (0.48–0.81) and Fe (0.46–0.79) except a low heritability for Fe observed for 7th HPYT (0.15). Grain yield was positively correlated with the number of tillers per m2, while negatively correlated with days to heading and maturity, grain iron, grain weight per spike, and thousand grain weight. The grain zinc and iron concentration were positively correlated, suggesting that the simultaneous improvement of both micronutrients is possible through wheat breeding. Extensive testing of CIMMYT derived high Zn wheat lines in Nepal led to the release of five biofortified wheat varieties in 2020 with superior yield, better disease resistance, and 30–40% increased grain Zn and adaptable to a range of wheat growing regions in the country – from the hotter lowland, or Terai, regions to the dry mid- and high-elevation areas.
Metabolomic Analysis Identifies Differences Between Wild and Domesticated Chili Pepper Fruits During Development (Capsicum annuum L.)
Authors: Cervantes-Hernández Felipe , Ochoa-Alejo Neftalí , Martínez Octavio , Ordaz-Ortiz José Juan
Published: June 2022

Capsicum spp. members are a rich source of specialized compounds due to their secondary metabolism. Some metabolic pathways have suffered modifications during the domestication process and improvement of agricultural traits. Here, we compared non-targeted LC–MS profiles from several areas: wild accessions (C. annuum L. var. glabriusculum), domesticated cultivars (C. annuum L.), and the F1 progeny of a domesticated, and a wild accession cross (in both directions) throughout seven stages of fruit development of chili pepper fruits. The main detected differences were in glycerophospholipid metabolism, flavone and flavonol biosynthesis, sphingolipid metabolism, and cutin biosynthesis. The domesticated group exhibited a higher abundance in 12′-apo-β-carotenal, among others capsorubin, and β-tocopherol. Palmitic acid and derivates, terpenoids, and quercitrin were prevalent in the wild accessions. F1 progeny showed a higher abundance of capsaicin, glycol stearate, and soyacerebroside I. This work supports evidence of the side-affectation of trait selection over the metabolism of chili pepper fruit development. Furthermore, it was also observed that there was a possible heterosis effect over the secondary metabolism in the F1 progeny.