bluuebunny/crossref_metadata_2025 huggingface dataset:
RETRACTED: Prognostic influence of PD-1/PD-L1 suppressors in combination with chemotherapeutic agents for non-small cell pulmonary carcinoma: system review and meta-analysis
Authors: Shen Min , Lu Chunxia , Gao Jie
Published: April 2023

Background

Lung cancer is a common malignant tumor, which is seriously harmful to human life and health. Nowadays, it has gradually become one of the best treatments for non-small cell lung cancer (NSCLC) to combine immunotherapy and chemotherapy, and its clinical efficacy is preliminary. Nevertheless, substantial differences exist between various studies and various indicators. Despite their unconvincing results, high-quality research evidence is needed to support them. In this case, further correlative studies are necessary to investigate the prognostic outcomes of PD-1/PD-L1 suppressors in combination with chemotherapeutic drugs in NSCLC.

Methods

The online public databases were searchable for the clinical trials that consisted of NSCLC patients who had concluded their chemotherapy and who had accepted PD-1/PD-L1 suppressors. The time-span of the search spanned from the beginning to the end of the database. Two investigators retrieved the data independently. RevMan 5.3 statistical software was utilized for the assessment of bias risk. The software followed the Cochrane Handbook 5.3 guidelines.

Results

There were seven clinically controlled studies with 2781 NSCLC samples finally included in this study. A meta-analysis of the post-treatment overall response rate (ORR) was undertaken. A remarkably higher ORR rate was observed in the study group (p<0.05). Study participants had a noticeably longer PFS (HR=0.61, 95% CI=0.54-0.70, P<0.00001). Study participants had markedly longer overall survival (OS) (HR=0.651, 95% CI=0.52-0.82, P<0.05). The incidence of adverse events (AEs) of Grade 3 or above was not clinically clearly different (P>0.05), as demonstrated by the incidence of AEs. The funnel plots were separately charted in accordance with ORR rate, PFE, OS, and Grade 3 AEs. The majority of the funnel plots were symmetrical and a minority of funnel plots were asymmetrical, indicating the heterogeneity of research and the limited evidence available may lead to some publication bias in the contained literature.

Conclusion

The combined PD-1/PD-L1 inhibitors with conventional chemotherapy can dramatically elevate the prognosis of NSCLC patients, obviously enhancing the ORR rate and prolonging their PFS and OS. Furthermore, it was found that adding PD-1/PD-L1 inhibitors to conventional chemotherapy did not result in any additional adverse effects.
Kruppel-like factor 8 regulates triple negative breast cancer stem cell-like activity
Authors: Le Minh Giang , Esquea Emily M. , Dhameliya Tejsi T. , Merzy Jessica , Lee Mi-Hye , Ball Lauren E. , Reginato Mauricio J.
Published: April 2023

Introduction

Breast tumor development is regulated by a sub-population of breast cancer cells, termed cancer stem-like cells (CSC), which are capable of self-renewing and differentiating, and are involved in promoting breast cancer invasion, metastasis, drug resistance and relapse. CSCs are highly adaptable, capable of reprogramming their own metabolism and signaling activity in response to stimuli within the tumor microenvironment. Recently, the nutrient sensor O-GlcNAc transferase (OGT) and O-GlcNAcylation was shown to be enriched in CSC populations, where it promotes the stemness and tumorigenesis of breast cancer cells in vitro and in vivo. This enrichment was associated with upregulation of the transcription factor Kruppel-like-factor 8 (KLF8) suggesting a potential role of KLF8 in regulating CSCs properties.

Methods

Triple-negative breast cancer cells were genetically modified to generate KLF8 overexpressing or KLF8 knock-down cells. Cancer cells, control or with altered KLF8 expression were analyzed to assess mammosphere formation efficiency, CSCs frequency and expression of CSCs factors. Tumor growth in vivo of control or KLF8 knock-down cells was assessed by fat-pad injection of these cell in immunocompromised mice.

Results

Here, we show that KLF8 is required and sufficient for regulating CSC phenotypes and regulating transcription factors SOX2, NANOG, OCT4 and c-MYC. KLF8 levels are associated with chemoresistance in triple negative breast cancer patients and overexpression in breast cancer cells increased paclitaxel resistance. KLF8 and OGT co-regulate each other to form a feed-forward loop to promote CSCs phenotype and mammosphere formation of breast cancer cells.

Discussion

These results suggest a critical role of KLF8 and OGT in promoting CSCs and cancer progression, that may serve as potential targets for developing strategy to target CSCs specifically.
Prognostic value of SLC4A4 and its correlation with the microsatellite instability in colorectal cancer
Authors: Rui Shaorui , Wang Dong , Huang Yong , Xu Jingyun , Zhou Hailang , Zhang Hesong
Published: April 2023

Objective

To explore new biomarkers related to microsatellite instability in order to better predict prognosis and guide medication.

Methods

The “limma” R package was used to identify differentially expressed genes in GSE24514, and then weighted correlation network analysis was used to select key genes. Different cell types in the tumor microenvironment were identified and analyzed by single-cell sequencing, with a Lasso regression model used to screen prognostic variables. Furthermore, the correlation between microsatellite instability and potential prognostic variables was explored, as well as the expression characteristics and clinical characteristics of the prognostic variables in the TCGA, UALCAN, and HPA databases. PCR assay was used to investigate the expression of SLC4A4 in colorectal cancer cell lines. Finally, we further verified the expression of SLC4A4 by immunohistochemistry.

Results

First, 844 differentially expressed genes in GSE24514 were identified. Subsequently, weighted co-expression network analysis (WGCNA) of GSE24514 obtained all the genes significantly associated with microsatellite instability (MSI), a total of 1452. Analysis of GSE166555 single cell sequencing data set yielded 1564 differentially expressed genes. The gene sets obtained from the above three analysis processes were intersected, and 174 genes were finally obtained. The Lasso regression model revealed two potential prognostic genes, TIMP1 and SLC4A4, of which, there was a stronger correlation between microsatellite instability and SLC4A4. The mRNA and protein expression of SLC4A4 was significantly decreased in tumors, and patients with low SLC4A4 expression had a poor prognosis. In addition, SLC4A4 was specifically expressed in epithelial cells. In the microenvironment of colorectal cancer, malignant cells have a strong interaction with different stromal cells. PCR showed that SLC4A4 was significantly down-regulated in colorectal cancer cell lines Caco-2, HCT116 and HT29 compared with normal control NCM460 cell lines. Immunohistochemistry also showed low expression of SLC4A4 in colorectal cancer.

Conclusion

SLC4A4, as a tumor suppressor gene, is significantly downregulated and positively correlated with microsatellite instability, thus it may be combined with microsatellite instability to guide colorectal cancer treatment.
Positive allosteric adenosine A2A receptor modulation suppresses insomnia associated with mania- and schizophrenia-like behaviors in mice
Authors: Lin Yang , Roy Koustav , Ioka Shuji , Otani Rintaro , Amezawa Mao , Ishikawa Yukiko , Cherasse Yoan , Kaushik Mahesh K. , Klewe-Nebenius Daniela , Zhou Li , Yanagisawa Masashi , Oishi Yo , Saitoh Tsuyoshi , Lazarus Michael
Published: April 2023

Background: Insomnia is associated with psychiatric illnesses such as bipolar disorder or schizophrenia. Treating insomnia improves psychotic symptoms severity, quality of life, and functional outcomes. Patients with psychiatric disorders are often dissatisfied with the available therapeutic options for their insomnia. In contrast, positive allosteric modulation of adenosine A2A receptors (A2ARs) leads to slow-wave sleep without cardiovascular side effects in contrast to A2AR agonists.

Methods: We investigated the hypnotic effects of A2AR positive allosteric modulators (PAMs) in mice with mania-like behavior produced by ablating GABAergic neurons in the ventral medial midbrain/pons area and in a mouse model of schizophrenia by knocking out of microtubule-associated protein 6. We also compared the properties of sleep induced by A2AR PAMs in mice with mania-like behavior with those induced by DORA-22, a dual orexin receptor antagonist that improves sleep in pre-clinical models, and the benzodiazepine diazepam.

Results: A2AR PAMs suppress insomnia associated with mania- or schizophrenia-like behaviors in mice. A2AR PAM-mediated suppression of insomnia in mice with mania-like behavior was similar to that mediated by DORA-22, and, unlike diazepam, did not result in abnormal sleep.

Conclusion: A2AR allosteric modulation may represent a new therapeutic avenue for sleep disruption associated with bipolar disorder or psychosis.
A perspective of immunotherapy for acute myeloid leukemia: Current advances and challenges
Authors: Chen Ying , Wang Jishi , Zhang Fengqi , Liu Ping
Published: April 2023

During the last decade, the underlying pathogenic mechanisms of acute myeloid leukemia (AML) have been the subject of extensive study which has considerably increased our understanding of the disease. However, both resistance to chemotherapy and disease relapse remain the principal obstacles to successful treatment. Because of acute and chronic undesirable effects frequently associated with conventional cytotoxic chemotherapy, consolidation chemotherapy is not feasible, especially for elderly patients, which has attracted a growing body of research to attempt to tackle this problem. Immunotherapies for acute myeloid leukemia, including immune checkpoint inhibitors, monoclonal antibodies, dendritic cell (DC) vaccines, together with T-cell therapy based on engineered antigen receptor have been developed recently. Our review presents the recent progress in immunotherapy for the treatment of AML and discusses effective therapies that have the most potential and major challenges.
Specificity for the correlation between the body surface and viscera in the pathological state of COPD: A prospective, controlled, and assessor-blinded trial
Authors: Jiang Yongliang , Hu Hantong , He Xiaofen , Li Xiaoyu , Zhang Yajun , Lou Jiali , Wu Yuanyuan , Fang Junfan , Shao Xiaomei , Fang Jianqiao
Published: April 2023

Background: The association between the body surface and viscera remains obscure, but a better understanding of the body surface-viscera correlation will maximize its diagnostic and therapeutic values in clinical practice. Therefore, this study aimed to investigate the specificity of body surface-viscera correlation in the pathological state.

Methods: The study subjects included 40 participants with chronic obstructive pulmonary disease (COPD) in the COPD group and 40 age-matched healthy participants in the healthy control group. Laser Doppler flowmetry, infrared thermography, and functional near-infrared spectroscopy were respectively adopted to measure 1) the perfusion unit (PU), 2) temperature, and 3) regional oxygen saturation (rSO2) of four specific sites distributed in the heart and lung meridians. These three outcome measures reflected the microcirculatory, thermal, and metabolic characteristics, respectively.

Results: Regarding the microcirculatory and thermal characteristics of the body surface, the PU and temperature of specific sites on the body surface [i.e., Taiyuan (LU9) and Chize (LU5) in the lung meridian] in the COPD group were significantly increased compared with healthy controls (p < 0.05), whereas PU and temperature of other sites in the heart meridian [i.e., Shenmen (HT7) and Shaohai (HT3)] did not change significantly (p > 0.05). Regarding the metabolic characteristics, rSO2 of specific sites in the lung meridian [i.e., Taiyuan (LU9) and Chize (LU5)] and Shaohai (HT3) of the heart meridian in the COPD group was significantly decreased compared with healthy controls (p < 0.01), whereas rSO2 of Shenmen (HT7) in the heart meridian did not change significantly (p > 0.05).

Conclusion: In the disease state of COPD, the microcirculatory, thermal, and metabolic characteristics of specific sites on the body surface in the lung meridian generally manifest more significant changes than those in the heart meridian, thereby supporting relative specificity for the body surface-viscera correlation in the pathological state.
Heel riser height and slope gradient influence the physiology of ski mountaineering—A laboratory study
Authors: Lasshofer Michael , Seifert John , Wörndle Anna-Maria , Stöggl Thomas
Published: April 2023

In ski mountaineering it is the goal to reach the top of a mountain by sheer muscle force. The specific equipment (flexible boot, only toe fixated binding, and a skin on the ski to prevent from slipping backwards) enables the skier to move up the hill ergonomically, where the heel part of the binding offers a special adaptation possibility. The so-called riser height supports the heel standing height and can be adjusted to individually preferred settings. General recommendations suggest using lower heel support in flat ascents and higher heel support in steep ascents to maintain upright posture and lower the strain. Still, it remains unclear whether the application of riser height affects the physiological response during ski mountaineering. This study was designed to investigate the effects of riser height on physiological response during indoor ski mountaineering. Nineteen participants took part in the study and walked on a treadmill with ski mountaineering equipment. The three available riser heights (low, medium, and high) were applied randomized at 8%, 16%, and 24% gradient. Results show that global physiological measurements like heart rate (p = 0.34), oxygen uptake (p = 0.26) or blood lactate (p = 0.38) values were not affected by changes in riser height. But local measurements of muscle oxygen saturation were affected by the riser height. Additionally comfort and rating of perceived exertion were also prone to changes in riser height. These results suggest differences on local measurements and perceived parameters, while global physiological measurements did not change. The results are in line with the existing recommendations but need to be confirmed in an outdoor setting as well.
Predicting the metabolic cost of exoskeleton-assisted squatting using foot pressure features and machine learning
Authors: Ramadurai Sruthi , Jeong Heejin , Kim Myunghee
Published: April 2023

Introduction: Recent studies found that wearable exoskeletons can reduce physical effort and fatigue during squatting. In particular, subject-specific assistance helped to significantly reduce physical effort, shown by reduced metabolic cost, using human-in-the-loop optimization of the exoskeleton parameters. However, measuring metabolic cost using respiratory data has limitations, such as long estimation times, presence of noise, and user discomfort. A recent study suggests that foot contact forces can address those challenges and be used as an alternative metric to the metabolic cost to personalize wearable robot assistance during walking.

Methods: In this study, we propose that foot center of pressure (CoP) features can be used to estimate the metabolic cost of squatting using a machine learning method. Five subjects’ foot pressure and metabolic cost data were collected as they performed squats with an ankle exoskeleton at different assistance conditions in our prior study. In this study, we extracted statistical features from the CoP squat trajectories and fed them as input to a random forest model, with the metabolic cost as the output.

Results: The model predicted the metabolic cost with a mean error of 0.55 W/kg on unseen test data, with a high correlation (r = 0.89, p < 0.01) between the true and predicted cost. The features of the CoP trajectory in the medial-lateral direction of the foot (xCoP), which relate to ankle eversion-inversion, were found to be important and highly correlated with metabolic cost.

Conclusion: Our findings indicate that increased ankle eversion (outward roll of the ankle), which reflects a suboptimal squatting strategy, results in higher metabolic cost. Higher ankle eversion has been linked with the etiology of chronic lower limb injuries. Hence, a CoP-based cost function in human-in-the-loop optimization could offer several advantages, such as reduced estimation time, injury risk mitigation, and better user comfort.
Translation of therapeutic strategies to modulate B cell reponses from non-human primate models to human kidney transplantation
Authors: Knechtle Stuart , Kwun Jean , Song Shengli , Jackson Annette , Williams Kitza , Sanoff Scott
Published: April 2023

Using novel drugs targeting lymphocyte costimulation, cytokines, antibody, complement, and plasma cells, we have developed strategies in a non-human primate model to modulate the B cell response to incompatible kidney transplants. After more than two decades of research supported by mechanistic studies, this has resulted in clinically relevant approaches that are currently enrolling in clinical trials or preparing for such. In this manner, we aim to address the problems of HLA sensitization for very highly sensitized patients awaiting transplantation and the unmet need of effective treatment for antibody-mediated rejection.
Place of residence and coach-athlete relationship predict drop-out from competitive cross-country skiing
Authors: Schmid Marit Anita , Solli Guro Strøm , Talsnes Rune Kjøsen , Moen Frode
Published: April 2023

The current study investigated whether factors such as living residence, the coach-athlete working alliance, goal orientation, and intrinsic motivation could explain drop-out, and whether these factors differed between athletes included in the elite- vs. general sport programs during high school years. In total 257 cross-country skiers, graduated from three different Norwegian Top Sport schools during the period from 2015 to 2019, were recruited to retrospectively investigate their experiences related to the time period when they participated in programs for cross-country skiing at high school. In total 116 of these athletes completed an online survey including validated and standardized instruments for the assessment of the coach-athlete working alliance (CAWAI), goal orientation (GO), perceived satisfaction with their performances (PAP) and intrinsic motivation (IM). The results showed that 84% of the athletes had dropped out from cross-country skiing, while 16% were still active. The highest ranked fixed statements of causes for drop-out was “a natural choice” (3.79 ± 1.11), “priority of education or work” (3.61 ± 1.30), “lack of motivation” (3.49 ± 1.28), “negative performance development” (3.46 ± 1.18), and “challenges with health” (3.25 ± 1.54). There were significant differences between active and drop-out in scores for reciprocity between the coaches' and the athletes' perceptions of goals (CAWAI-goal; 5.87 ± .98 vs. 5.07 ± 1.15;p = .004), the coach-athlete relationship bond (CAWAI-bond; 6.08 ± .91 vs. 5.07 ± 1.38;p = .001), and tasks chosen to reach the defined goals (CAWAI-task; 5.61 ± .92 vs. 4.90 ± 1.09;p = .006). Furthermore, active athletes had higher mastery orientation (22.11 ± 2.88 vs. 20.00 ± 3.74;p = .010). A hierarchical binary logistic regression analysis showed that place of residence and the coach-athlete working alliance were significant predictors of drop-out while mastery and performance goal orientation or intrinsic motivation were not significant. All five predictors explained 23% of the variability in drop out from cross-country skiing. Overall, 58% and 42% of the athletes participated in the elite and general programs for cross-country skiing during high school, respectively. The athletes that took part in the elite programs reported significantly stronger coach-athlete working alliances (CAWAI-sum; 14.46±3.10 vs. 14.28±3.37;p = .000), higher mastery orientation (21.19±3.50 vs. 19.36±3.66;p = .008), and performance satisfaction (PAP; 19.17±5.98 vs. 15.69±5.19;p = .001) compared to the athletes attending general programs. The results are discussed in terms of existing knowledge on how place of residence, the coach-athlete working alliance, goal orientation, performances, and motivation might impact drop-out in cross-country skiing.
Operative management and outcomes in patients with myxomas: A single-center experience
Authors: Alhasso Ahmed Abdulfattah , Ahmed Okba F. , Mohammed-Saeed Dana H. , Kakamad Fahmi H. , Almodhaffer Saif S. , Zaid Zaid A. , Abdullah Hiwa O. , Ali Razhan K. , Kakamad Suhaib H. , Omar Diyar A. , Abdalla Berun A. , Mohammed Shvan H. , Mustafa Mohammed Q.
Published: April 2023

Background

Cardiac myxoma is a rare cardiac tumor that may be asymptomatic or can cause embolization or intracardiac obstruction, leading to heart failure, sudden cardiac death, and arrhythmia. This study aims to report an 11-year experience of a single center in the management of cardiac myxoma.

Method

This study is a single-center retrospective case series. Eighty cases of cardiac myxoma were collected in Ibn Albitar's specialized center for cardiac surgery. Transthoracic echocardiography was used to make the preoperative diagnosis in all patients. The surgeries were undertaken through the standard approach of a median sternotomy. All four cardiac chambers were thoroughly explored for additional myxomas. The major objective of the operations was complete tumor resection.

Result

The mean age of the patients was 46.3 years. Females (67.5%) were predominant over males (32.5%). Shortness of breath was the most common symptom (86.25%). The left atrium was the most affected site (83.75%), followed by the right atrium (13.75%). Coronary artery bypass grafting was required as the secondary or associated intervention in 19 (23.75%) cases. The recurrence rate was 11.25%, with a mortality rate of 3.75%.

Conclusion

Recurrence and tumor embolism are risks of surgical intervention for myxoma. Good preparation using transthoracic echocardiography as a diagnostic tool and standard median sternotomy to complete resection of the tumors can decrease the rate of recurrence, embolism, and even mortality.
Renal primitive neuroectodermal tumor: A rare case with a good prognosis
Authors: Chen Hanmin , Li Yanmin , Zeng Qingming , Wu Gengqing
Published: April 2023

Background

Renal primitive neuroectodermal tumor (rPNET) has the characteristics of a difficult preoperative diagnosis, a high degree of malignancy, easy early metastasis or postoperative recurrence, a poor prognosis, and so on. However, rPNET that has no metastasis before surgery can have a good survival prognosis only after radical surgical resection.

Methods

We report the case of a 14-year-old male patient with a renal tumor who underwent open radical left nephrectomy without radiotherapy or chemotherapy before or after surgery, as confirmed by postoperative pathological results. The prognosis was followed up by a regular review of the chest and whole abdomen on CT, hematuria analysis, renal function, and electrolytes according to the guidelines for renal cancer.

Results

Postoperative pathological results confirmed rPNET; no adjuvant radiotherapy or chemotherapy were performed after surgery; no tumor recurrence or metastasis were observed during the follow-up of nearly 5 years.

Conclusions

Despite the high degree of rPNET malignancy, patients without metastases before surgery can still obtain a good survival prognosis through timely radical surgery.
In vitro effects of different levels of quebracho and chestnut tannins on rumen methane production, fermentation parameters, and microbiota
Authors: Battelli Marco , Colombini Stefania , Parma Pietro , Galassi Gianluca , Crovetto Gianni Matteo , Spanghero Mauro , Pravettoni Davide , Zanzani Sergio Aurelio , Manfredi Maria Teresa , Rapetti Luca
Published: April 2023

Both condensed and hydrolysable tannins (CTs and HTs, respectively) have the ability to reduce enteric CH4 production in ruminants. However, the precise mechanism of action is not fully understood. Among the proposed hypotheses are the reduction of ruminal digestibility, direct control action on protozoa, reduction of archaea, and a hydrogen sink mechanism. In this in vitro study, which simulated rumen fermentation, two additives, one containing CTs (70% based on DM) from quebracho and one with HTs (75% based on DM) from chestnut, at four levels of inclusion (2, 4, 6, 8% on an as-fed basis) were added to the fermentation substrate and tested against a negative control. Both types of tannins significantly reduced total gas (GP) and CH4 (ml/g DM) production during the 48 h of incubation. The lower GP and CH4 production levels were linked to the reduction in dry matter digestibility caused by CTs and HTs. Conversely, no significant differences were observed for the protozoan and archaeal populations, suggesting a low direct effect of tannins on these rumen microorganisms in vitro. However, both types of tannins had negative correlations for the families Bacteroidales_BS11 and F082 and positive correlations for the genera Prevotella and Succinivibrio. Regarding the fermentation parameters, no differences were observed for pH and total volatile fatty acid production, while both CTs and HTs linearly reduced the NH3 content. CTs from quebracho were more effective in reducing CH4 production than HTs from chestnut. However, for both types of tannins, the reduction in CH4 production was always associated with a lower digestibility without any changes in archaea or protozoa. Due to the high variability of tannins, further studies investigating the chemical structure of the compounds and their mechanisms of action are needed to understand the different results reported in the literature.
Relationship Between Alcohol Consumption and Risky Sexual Behaviors Among Adolescents and Young Adults: A Meta-Analysis
Authors: Cho Hyang-Soon , Yang Youngran
Published: April 2023

Objectives: Adolescents exposed to alcohol have increased risky sexual behaviors (RSBs); however, the association between alcohol consumption and RSBs has to be systematically and quantitatively reviewed. We conducted a meta-analysis of the literature to systematically and quantitatively review the association between alcohol consumption and RSBs in adolescents and young adults.

Methods: We searched for qualified articles published from 2000 to 2020 and calculated pooled odds ratios (ORs) using the random-effect model. We also conducted meta-regression and sensitivity analyses to identify potential heterogeneity moderators.

Results: The meta-analysis of 50 studies involving 465,595 adolescents and young adults indicated that alcohol consumption was significantly associated with early sexual initiation (OR = 1.958, 95% confidence interval (CI) = 1.635–2.346), inconsistent condom use (OR = 1.228, 95% CI = 1.114–1.354), and having multiple sexual partners (OR = 1.722, 95% CI = 1.525–1.945).

Conclusion: Alcohol consumption is strongly associated with RSBs, including early sexual initiation, inconsistent condom use, and multiple sexual partners among adolescents and young adults. To prevent the adverse consequences of alcohol consumption, drinking prevention programs should be initiated at an early age and supported by homes, schools, and communities.
Rosetta Stone for Cancer Cure: Comparison of the Anticancer Capacity of Endogenous Estrogens, Synthetic Estrogens and Antiestrogens
Authors: Suba Zsuzsanna
Published: April 2023

This work presents the history of the recognition of principal regulatory capacities of estrogen hormones having been mistakenly regarded as breast cancer promoting agents for more than 120 years. Comprehensive analysis of the results of clinical, epidemiological, immunological and molecular studies justified that endogenous estrogens are the principal regulators of embryonic development, survival and reproduction via orchestrating appropriate expression and even edition of all genes in mammalians. Medical use of chemically modified synthetic estrogens caused toxic complications; thromboembolic events and increased cancer risk in female organs as they proved to be endocrine disruptors deregulating estrogen receptors (ERs) rather than their activators. Synthetic estrogen treatment exhibits ambiguous correlations with cancer risk at different sites, which may be attributed to an inhibition of the unliganded activation of estrogen receptors (ERs) coupled with compensatory liganded activation. The principle of estrogen induced breast cancer led to the introduction of antiestrogen therapies against this tumor; inhibition of the liganded activation of estrogen receptors and aromatase enzyme activity. The initial enthusiasm turned into disappointment as the majority of breast cancers proved to be primarily resistant to antiestrogens. In addition, nearly all patients showing earlier good tumor responses to endocrine therapy, later experienced secondary resistance leading to metastatic disease and fatal outcome. Studying the molecular events in tumors responsive and unresponsive to antiestrogen therapy, it was illuminated that a complete inhibition of liganded ER activation stimulates the growth of cancers, while a successful compensatory upregulation of estrogen signal may achieve DNA restoration, tumor regression and patient’s survival. Recognition of the principal role of endogenous estrogens in gene expression, gene edition and DNA repair, estrogen treatment and stimulation of ER expression in patients may bring about a great turn in medical practice.
Conceptual Model for Assessing Logistics Maturity in Smart City Dimensions
Authors: Pereira Glauber Ruan Barbosa , Guimarães Luciana Gondim de Almeida , Cimon Yan , Da Silva Barreto Lais Karla , Hermann Nodari Cristine
Published: April 2023

The advancement of new technologies and the increasingly inseparable presence of logistics systems in the daily life of cities, industries, companies, and society has been modifying how logistics processes are implemented in these environments based on technological innovations, internet, virtual businesses, mobility, and the use of multi-channel distribution. Together with these changes, urban centers have been connecting to the smart city concept as the understanding of this theme advances into the debate and improvements in the agendas of either public or private management. This research proposes a conceptual model for evaluating logistics maturity in the smart city dimensions. The method has a qualitative, exploratory, and descriptive approach, supported by the Delphi method, which uses a questionnaire and interview as a data collection instrument with specialists on the subject. We identified that qualifying logistics in the urban environment is complex and requires a specialized look at identifying cities’ structural, geographic, regional, social, and environmental characteristics. As a social–technological contribution, the proposition of the logistics maturity assessment scale in smart city dimensions can serve as an evaluative model of logistics, which means helping in urban planning and strategic management of cities, offering smarter solutions to the realities of urban spaces.
Flight Parameter—Wind Vortex Characteristic Control Model of a Four-Multirotor Unmanned Aerial Vehicle Operating in Pesticide Spraying of Rice
Authors: Liu Zhijie , Fan Gangao , Ye Siyan , Zhang Zhixun , Wu Han , Long Bo , Li Huifen , Cheng Hui , Wu Longmei , Li Jiyu
Published: April 2023

The downwash airflow generated by the rotors can enhance the penetration of pesticide droplets, allowing them to penetrate deeper into the canopy and more comprehensively control pests. Downwash air will produce a “wind vortex” in plant canopy, and the parameters of a “wind vortex” represent the effect of pesticide deposition to a certain extent. To obtain the corresponding relationship between wind vortices and flight parameters and control the effect of pesticide spraying, this paper carried out unmanned aerial vehicle (UAV) flight experiments in the field. Wind vortices were generated in rice canopy by downwash airflow, and the parameters of wind vortices were obtained by identifying wind-vortex images using the inter-frame difference method. The wind-vortex parameter control model was established, which can calculate the altitude and speed of the UAV when applying pesticide according to the target wind-vortex parameter. The deviations in the altitude were determined to be 0.67 and 0.43 m, and the deviations in the speed were 0.29 and 0.35 m/s during downwind and headwind UAV operations, respectively. The model relation functions were established, and their accuracies were found to be 97.1%, 92.3%, 69%, and 58% (downwind), and 97%, 78.4%, 62%, and 57% (upwind), respectively, indicating that downwind UAV operation leads to a clear relation between the wind-vortex parameters and the UAV-flight parameters. The model establishes the corresponding relationship between the wind-vortex parameters and flight parameters, which provides a theoretical basis for studying the precise application control method of UAV.
Development of SSR Molecular Markers and Genetic Diversity Analysis of TPS Gene Family in Chimonanthus praecox
Authors: Fu Xuemei , Yang Nan , Du Yongqin , Kamran Hafiz Muhammad , Wang Huabo , Chen Shaoyuan , Chen Longqing
Published: April 2023

Terpene synthase (TPS) plays a key role in the biosynthesis of terpenoids, which are the most important components of the volatile compounds of wintersweet (Chimonanthus praecox). In this study, 52 CpTPS genes were found in wintersweet which were divided into 5 subfamilies. We identified 146 SSRs in the CpTPS genes, and obtained 33 pairs of SSR primers with good polymorphism through amplification in 6 wintersweet samples. Then, these primers were amplified in 69 samples from China’s main wintersweet production areas. Through structural analysis, 69 samples were divided into 2 clusters, and were divided into 4 groups in a genetic cluster analysis, of which SH-33 and SW were separate groups. Through AMOVA analysis, it was found that the variation mainly occurred in the population, and that the gene flow between populations was Nm > 1, so it might lead to population differentiation. In other words, these findings provided useful information for the biosynthesis of terpenoids, the construction of a genetic linkage map, the detection of quantitative trait loci, marker-assisted selection and other aspects of wintersweet.
Agricultural Combine Remaining Value Forecasting Methodology and Model (and Derived Tool)
Authors: Herranz-Matey Ivan , Ruiz-Garcia Luis
Published: April 2023

Harvesting is an integral component of the agricultural cycle, necessitating the use of high-performance grain harvester combines, which are utilized for a short period each year. Given the seasonality and significant cost involved, list prices ranging from a quarter to almost a million euros, a fact-based investment assessment decision-making process is essential. However, there is a paucity of research studies forecasting the remaining value of grain harvester combines in recent years. This study proposes a straightforward methodology based on public information that employs various parametric and non-parametric models to develop a robust and user-friendly model that can assist decision makers, such as farmers, contractors, sellers, and finance and insurance entities, in optimizing their harvesting operations. The model employs a power regression mode, with RMSE of 1.574 and RSqAdj of 0.8457 results, to provide accurate and reliable insights for informed decision-making. The robust model transparency enables us to easily create a mainstreamed spreadsheet-based dashboard tool.
Evaluating the Canopy Chlorophyll Density of Maize at the Whole Growth Stage Based on Multi-Scale UAV Image Feature Fusion and Machine Learning Methods
Authors: Zhou Lili , Nie Chenwei , Su Tao , Xu Xiaobin , Song Yang , Yin Dameng , Liu Shuaibing , Liu Yadong , Bai Yi , Jia Xiao , Jin Xiuliang
Published: April 2023

Maize is one of the main grain reserve crops, which directly affects the food security of the country. It is extremely important to evaluate the growth status of maize in a timely and accurate manner. Canopy Chlorophyll Density (CCD) is closely related to crop health status. A timely and accurate estimation of CCD is helpful for managers to take measures to avoid yield loss. Thus, many methods have been developed to estimate CCD with remote sensing data. However, the relationship between the CCD and the features used in these CCD estimation methods at different growth stages is unclear. In addition, the CCD was directly estimated from remote sensing data in most previous studies. If the CCD can be accurately estimated from the estimation results of Leaf Chlorophyll Density (LCD) and Leaf Area Index (LAI) remains to be explored. In this study, Random Forest (RF), Support Vector Machines (SVM), and Multivariable Linear Regression (MLR) were used to develop CCD, LCD, and LAI estimation models by integrating multiple features derived from unmanned aerial vehicle (UAV) multispectral images. Firstly, the performances of the RF, SVM, and MLR trained over spectral features (including vegetation indices and band reflectance; dataset I), texture features (dataset II), wavelet coefficient features (dataset III), and multiple features (dataset IV, including all the above datasets) were analyzed, respectively. Secondly, the CCDP was calculated from the estimated LCD and estimated LAI, and then the CCD was estimated based on multiple features and the CCDP was compared. The results show that the correlation between CCD and different features is significantly different at every growth stage. The RF model trained over dataset IV yielded the best performance for the estimation of LCD, LAI, and CCD (R2 values were 0.91, 0.97, and 0.97, and RMSE values were 6.59 μg/cm2, 0.35, and 24.85 μg/cm2). The CCD directly estimated from dataset IV is slightly closer to the ground truth CCD than the CCDP (R2 = 0.96, RMSE = 26.85 μg/cm2) calculated from LCD and LAI. The results indicated that the CCD of maize can be accurately estimated from multiple multispectral image features at the whole growth stage, and both CCD estimation strategies can be used to estimate the CCD accurately. This study provides a new reference for accurate CCD evaluation in precision agriculture.
Fungicide Scent Pollution Disrupts Floral Search-and-Selection in the Bumblebee Bombus impatiens
Authors: Yousry Nour , Henderson Paige , Sprayberry Jordanna
Published: April 2023

Bumblebees are valuable generalist pollinators. However, micro- and macro-stressors on bumblebees negatively impact both foraging efficiency and pollination efficacy. Given that colonies have a resource threshold for successful reproduction, factors that decrease foraging efficiency could negatively impact conservation efforts. Recently, agrochemical odor pollution has been shown to hinder floral odor learning and recognition in Bombus impatiens via an associative odor learning assay (FMPER). These results may have implications for the field foraging behavior of bumblebees. Building on this prior work, our study aimed to determine if negative effects of fungicides on associative odor learning and recognition scale up to negative impacts on actively foraging bumblebees. These experiments investigated whether the presence of a background fungicide odor (Reliant® Systemic Fungicide) impacts the location of a learned floral resource (lily of the valley-scented blue flowers) in a wind tunnel. Experiments were run with and without early access to visual cues to determine if fungicide odor pollution is more impactful on bees that are engaged in olfactory versus visual navigation. Fungicide odor pollution reduced landing frequency in both paradigms.
Screening Canola Genotypes for Resistance to Ammonium Toxicity
Authors: Al-Awad Omar Ali Shaban , Prendergast Kit Stasia , Robson Alan , Rengel Zed
Published: April 2023

Soil ammonium toxicity can decrease plant growth, and many crop species have low resistance to ammonium, including canola, an economically important crop. Different genotypes may differ in their resistance to ammonium toxicity, and therefore determining if there are genotypes that exhibit variation in their ability to tolerate soil ammonium is a research priority. Here, we evaluate how soil ammonium impacts canola root and shoot growth and characterise differences among canola genotypes in regard to resistance to ammonium toxicity. In the first experiment, eight ammonium chloride treatments and five calcium nitrate treatments were tested for their impact on the canola genotype Crusher TT, where high application (60 mg N/kg soil) significantly decreased the dry weight of canola shoots and roots and acidified the soil from pHCaCl2 5.9 to 5.6. In the second experiment, 30 canola genotypes were screened at selected concentrations of NH4+-N, using nitrate as the control. There was wide variation among genotypes in sensitivity to high NH4+-N application. Genotypes G16, G26, and G29 had greater shoot dry weights and the highest shoot N concentration of all genotypes, and G16, G26, and G28 had root dry weight up to 35% higher at high soil NH4+-N compared with other genotypes. In contrast, genotypes G3, G13, and G30 showed the largest reduction in shoot weight, and genotypes G13, G23, and G30 showed the largest reduction in root weight at high NH4+-N application. Residual NH4+-N/kg soil in soil was higher for sensitive than resistant genotypes, suggesting lower NH4+-N use in the former. These results reveal the potential for selecting canola genotypes that are resistant to high NH4+-N concentrations in soil.
Preharvest Treatments with Low-Risk Plant Protection Products Can Help Apple Growers Fulfill the Demands of Supermarket Chains Regarding Pesticide Residues and Marketing Apples under 0-Residue Brands
Authors: Paušič Andrej , Roškarič Mihaela , Lešnik Mario
Published: April 2023

As a result of worried consumer pressure, European supermarket chains (ESC) have developed very strict rules about the number and concentration of pesticide active substance residues (AS) accepted in fruits. So-called fruit quality toxicological burden indicators were developed. If fruit suppliers do not comply with ESC requirements, their fruit is often rejected. It is becoming increasingly difficult for apple producers to meet all the requirements of the ESC, so they need new residue reduction tools. One of the options to lower the concentrations of residue on apples is a preharvest application of low-risk preparations (LRP) based on potassium bicarbonate (KHCO3) = PBC, coconut di-ethanol amide ((CH3(CH2)nC(=O)N(CH2CH2OH)2) = DEA, hydrogen peroxide (H2O2) = HP, and a mixture of microbes (EM) that have the ability to dissolve or disintegrate the AS residue. Trials were carried out to test the concept mentioned above. The application of LRP during the last four weeks of preharvest significantly reduced the residue concentration of pesticide AS in apples. Reduction rates among 25 active substances ranged from 0 to 100%, depending on the combination of LRP and AS. HP had the highest capacity to accelerate AS degradation, PB was the second most efficient, and DEA and EM displayed a low residue disintegration ability. The application of the tested LRP can enable apple growers to produce fruits with significantly lower residue concentrations and allows them to comply more successfully with strict ESC rules based on the calculations of toxicological burden indicators.
High-Throughput Classification and Counting of Vegetable Soybean Pods Based on Deep Learning
Authors: Zhang Chenxi , Lu Xu , Ma Huimin , Hu Yuhao , Zhang Shuainan , Ning Xiaomei , Hu Jianwei , Jiao Jun
Published: April 2023

Accurate identification of soybean pods is an important prerequisite for obtaining phenotypic traits such as effective pod number and seed number per plant. However, traditional image-processing methods are sensitive to light intensity, and feature-extraction methods are complex and unstable, which are not suitable for pod multi-classification tasks. In the context of smart agriculture, many experts and scholars use deep learning algorithm methods to obtain the phenotype of soybean pods, but empty pods and aborted seeds are often ignored in pod classification, resulting in certain errors in counting results. Therefore, a new classification method based on the number of effective and abortive seeds in soybean pods is proposed in this paper, and the non-maximum suppression parameters are adjusted. Finally, the method is verified. The results show that our classification counting method can effectively reduce the errors in pod and seed counting. At the same time, this paper designs a pod dataset based on multi-device capture, in which the training dataset after data augmentation has a total of 3216 images, and the distortion image test dataset, the high-density pods image test dataset, and the low-pixel image test dataset include 90 images, respectively. Finally, four object-detection models, Faster R-CNN, YOLOv3, YOLOv4, and YOLOX, are trained on the training dataset, and the recognition performance on the three test datasets is compared to select the best model. Among them, YOLOX has the best comprehensive performance, with a mean average accuracy (mAP) of 98.24%, 91.80%, and 90.27%, respectively. Experimental results show that our algorithm can quickly and accurately achieve the high-throughput counting of pods and seeds, and improve the efficiency of indoor seed testing of soybeans.
Integrated miRNA Changes in Canine Testis and Epididymis According to Age and Presence of Cryptorchidism
Authors: Kim Eun Pyo , Shin Jae-Ho , Kim Wan Hee , Kim Geon A.
Published: April 2023

In the present study, we aimed to investigate age-, cryptorchidism-, and testicular tumor-related changes in miRNAs in the testis and epididymis of dogs. Twelve healthy male dogs were divided into two groups: young (<1 year, n = 8) and old (>3 years, n = 4). Five dogs with unilateral cryptorchidism, one with a Sertoli cell tumor, and one with seminoma were referred to a veterinary hospital. After surgery, the testes and epididymis tails were collected. A high-throughput miRNA array analysis was performed to identify miRNAs affected by age, cryptorchidism, and testicular tumors. The expression of only cfa-miR-503 was downregulated in the epididymis of younger dogs, whereas the expression of 64 miRNAs was upregulated. Among them, the top five miRNAs were cfa-miR-26a, cfa-miR-200c, cfa-let-7c, cfa-let-7b, and cfa-let-7a. The expression of cfa-miR-148a and cfa-miR-497 was considerably lower in cryptorchid testis than in healthy dog testis. In the epididymis, the cfa-miR-1841 level was significantly decreased. We observed a significant difference in the expression of 26 cfa-miRNAs between testicular tumors and normal tissues. This study demonstrated that aging and cryptorchidism have a causal relationship with miRNA expression. The identified miRNAs may be candidate genes for male reproductive traits and could be applied in molecular breeding programs.