bluuebunny/crossref_metadata_2025 huggingface dataset:
Activating transcription factor 4-dependent hsa-miR-663a transcription mediates mTORC1/p70S6K1 signaling underleucine deprivation
Authors: Yamamura Junki , Ma Sihui , Jia Huijuan , Kato Hisanori
Published: August 2022

The mechanistic target of rapamycin complex 1 (mTORC1) is involved in nutrient-induced signaling and is a master regulator of cell growth and metabolism. Amino acid-deficient conditions affect mTORC1 activity; however, its upstream regulators warrant further investigation. MicroRNAs are key regulators of nutrient-related responses; therefore, the present study aimed to assess the leucine starvation-induced microRNA profile and its impact on mTORC1 activity. Transcriptome analysis of human hepatocellular carcinoma cells (HepG2) under leucine deprivation revealed that hsa-miR-663a and hsa-miR-1469 were altered in a transcription factor 4-dependent manner. Overexpression of these microRNAs induced phosphorylation of the ribosomal protein S6 kinase beta-1, a mTORC1 downstream target. Furthermore, hsa-miR-663a downregulated proline-rich Akt1 substrate of 40 kDa (PRAS40), one of the mTORC1 components. In summary, this study provides new insights into the regulatory role of microRNAs in amino acid metabolism and demonstrates alterations in microRNA profile under leucine deprivation in human hepatocytes.
Baduanjin’s impact on quality of life and sleep quality in breast cancer survivors receiving aromatase inhibitor therapy: a randomized controlled trial
Authors: Liao Jingwen , Chen Yanyu , Cai Li , Wang Kun , Wu Shenghui , Wu Lan , Song Bixiao , Hu Min , Hou Xiaohui
Published: August 2022

Purpose

The aim of the current study is to investigate the impact of Baduanjin, a traditional Chinese exercise, on quality of life and sleep quality in breast cancer survivors receiving aromatase inhibitor (AI) therapy.

Methods

A total of 72 breast cancer survivors who had received AI treatment for more3 than 6 months were enrolled in the current study using non-probability consecutive sampling procedure. Participants were randomly assigned in a 1:1 ratio to a 12-week Baduanjin exercise program or to a wait-list control group. The Baduanjin exercise group performed two 90-min supervised sessions per week. The primary outcomes were changes in quality of life measured by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30) and in sleep quality evaluated using the Pittsburgh Sleep Quality Index (PSQI).

Results

A total of 68 participants completed the trial (Baduanjin exercise group: n = 33; control group: n = 35). Baseline values for quality of life did not differ between groups. Both global quality of life and physical functioning scores increased significantly by 12.39 (P < 0.001) and 8.48 (P < 0.001) in the Baduanjin exercise group compared with those in the control. Overall PSQI score also decreased by 4.85 (P < 0.001) in the Baduanjin exercise group, whereas it increased by 0.34 in the control group.

Conclusion

Baduanjin exercise training led to improvement in the quality of life and sleep quality of breast cancer patients undergoing AI therapy.
Novel myeloma patient-derived xenograft models unveil the potency of anlotinib to overcome bortezomib resistance
Authors: Yue Yanhua , Cao Yang , Mao Xunyuan , Wang Fei , Fan Peng , Qian Long , Guo Shuxin , Li Feng , Guo Yanting , Chen Tongbing , Lin Yan , Dong Weimin , Liu Yue , Huang Yuhui , Gu Weiying
Published: August 2022

Multiple myeloma (MM) remains a common hematologic malignancy with a 10-year survival rate below 50%, which is largely due to disease relapse and resistance. The lack of a simple and practical approach to establish myeloma patient-derived xenograft (PDX) hampers translational myeloma research. Here, we successfully developed myeloma PDXs by subcutaneous inoculation of primary mononuclear cells from MM patients following series tumor tissue transplantations. Newly established myeloma PDXs retained essential cellular features of MM and recapitulated their original drug sensitivities as seen in the clinic. Notably, anlotinib therapy significantly suppressed the growth of myeloma PDXs even in bortezomib-resistant model. Anlotinib treatments polarized tumor-associated macrophages from an M2- to an M1-like phenotype, decreased tumor vascular function, and accelerated cell apoptosis in myeloma PDXs. Our preclinical work not only unveiled the potency of anlotinib to overcome bortezomib resistance, but also provided a more practical way to establish MM PDX to facilitate myeloma research.
Computer-aided diagnosis of cervical dysplasia using colposcopic images
Authors: Ma Jing-Hang , You Shang-Feng , Xue Ji-Sen , Li Xiao-Lin , Chen Yi-Yao , Hu Yan , Feng Zhen
Published: August 2022

Background

computer-aided diagnosis of medical images is becoming more significant in intelligent medicine. Colposcopy-guided biopsy with pathological diagnosis is the gold standard in diagnosing CIN and invasive cervical cancer. However, it struggles with its low sensitivity in differentiating cancer/HSIL from LSIL/normal, particularly in areas with a lack of skilled colposcopists and access to adequate medical resources.

Methods

the model used the auto-segmented colposcopic images to extract color and texture features using the T-test method. It then augmented minority data using the SMOTE method to balance the skewed class distribution. Finally, it used an RBF-SVM to generate a preliminary output. The results, integrating the TCT, HPV tests, and age, were combined into a naïve Bayes classifier for cervical lesion diagnosis.

Results

the multimodal machine learning model achieved physician-level performance (sensitivity: 51.2%, specificity: 86.9%, accuracy: 81.8%), and it could be interpreted by feature extraction and visualization. With the aid of the model, colposcopists improved the sensitivity from 53.7% to 70.7% with an acceptable specificity of 81.1% and accuracy of 79.6%.

Conclusion

using a computer-aided diagnosis system, physicians could identify cancer/HSIL with greater sensitivity, which guided biopsy to take timely treatment.
First case report of spontaneous biliary pleural fistula diagnosed using near infrared region I/II fluorescence of indocyanine green
Authors: Peng Yisheng , Fan Jun , Zhu Gang , Fang Cheng , Peng Fangyi , Zhang Zeyu , Tian Jie , Su Song , Yang Xiaoli , Li Bo
Published: August 2022

We report a rare case of spontaneous biliary pleural fistula in a patient whose diagnosis was aided by the use of near-infrared I/II fluorescence imaging. When both 99mTc-mebrofenin hepatobiliary scintigraphy and CT examination were diagnostically difficult, we found strong fluorescent signals in the patient’s pleural drainage fluid and sputum using NIR I/II fluorescence imaging, and therefore diagnosed the patient with a biliary pleural fistula. This provides a safe and effective test for diagnosing biliary pleural fistulas.
Epithelial–myoepithelial carcinoma of the nasopharynx: A case report and review of the literature
Authors: Zhang Wei , Wang Xiao-xiao , Wang Xiao-li , Zhang Yan , Li Xiu-feng , Li Yang , Cai Yuan-yuan , Ren Hui-qi , Zhang Yun-xiang , Hao Fu-rong
Published: August 2022

Background

Epithelial–myoepithelial carcinoma (EMCa) is a rare low-grade malignant tumor that most commonly occurs in the salivary glands, with approximately 320 cases having been reported worldwide. Here, we report the third case of EMCa occurring in the nasopharynx. Rare cases in the breast, pituitary gland, lacrimal gland, nose, paranasal sinus, nasal cavity, trachea and bronchus, lung, and even the pleura mediastinalis have also been reported. Histopathology and immunohistochemistry are useful for confirming the diagnosis of EMCa, which is characterized by biphasic tubular structures composed of inner ductal and outer clear myoepithelial cells and stains for different markers in each layer. However, because of the rarity of EMCa, the clinicopathological characteristics and treatment of these patients remain unclear.

Case presentation

We report a rare case of EMCa of the nasopharynx. A 51-year-old man presented with a 5-month history of pain while swallowing and aggravation accompanied by right ear tinnitus lasting for 1 month. Nasopharyngoscopy and magnetic resonance imaging (MRI) of the nasopharynx and neck revealed a 5.6 cm × 3.4 cm × 3.1 cm mass in the nasopharyngeal space, invasion of the right cavernous sinus, and lymph node enlargement in the right retropharyngeal space. On 17 April 2019, based on the histopathological and immunohistochemical features, a final diagnosis of EMCa of the right nasopharynx was made. The patient underwent concurrent chemoradiotherapy (CCRT), and his symptoms were relieved after treatment. On 10 January 2022, nasopharynx MRI and biopsy revealed local recurrence, but chest and abdominal computed tomography (CT) showed no obvious signs of metastasis. The local recurrence-free survival (LRFS) period was 33 months.

Conclusion

To the best of our knowledge, this is the third reported case of EMCa in the nasopharynx and the only case of EMCa in the nasopharynx treated with CCRT, and a partial response was achieved. Therefore, to improve the quality of life and prognosis of patients with unresectable tumors, we believe that CCRT is a suitable option. Further clinical observations are required to elucidate the pathophysiology and prognosis of EMCa.
Proton induced DNA double strand breaks at the Bragg peak: Evidence of enhanced LET effect
Authors: Frame Cara M. , Chen Yu , Gagnon Jonathan , Yuan Y. , Ma Tianjun , Dritschilo Anatoly , Pang Dalong
Published: August 2022

Purpose

To investigate DNA double strand breaks (DSBs) induced by therapeutic proton beams in plateau and Bragg peak to demonstrate DSB induction due to the higher LET in the Bragg peak.

Materials and Methods

pUC19 plasmid DNA samples were irradiated to doses of 1000 and 3000 Gy on a Mevion S250i proton system with a monoenergetic, 110 MeV, proton beam at depths of 2 and 9.4 cm, corresponding to a position on the plateau and distal Bragg peak of the beam, respectively. The irradiated DNA samples were imaged by atomic force microscopy for visualization of individual DNA molecules, either broken or intact, and quantification of the DNA fragment length distributions for each of the irradiated samples. Percentage of the broken DNA and average number of DSBs per DNA molecule were obtained.

Results

Compared to irradiation effects in the plateau region, DNA irradiated at the Bragg peak sustained more breakage at the same dose, yielding more short DNA fragments and higher numbers of DSB per DNA molecule.

Conclusion

The higher LET of proton beams at the Bragg peak results in more densely distributed DNA DSBs, which supports an underlying mechanism for the increased cell killing by protons at the Bragg peak.
Small molecule MMRi62 targets MDM4 for degradation and induces leukemic cell apoptosis regardless of p53 status
Authors: Lama Rati , Xu Chao , Galster Samuel L. , Querol-García Javier , Portwood Scott , Mavis Cory K. , Ruiz Federico M. , Martin Diana , Wu Jin , Giorgi Marianna C. , Bargonetti Jill , Wang Eunice S. , Hernandez-Ilizaliturri Francisco J. , Koudelka Gerald B. , Chemler Sherry R. , Muñoz Inés G. , Wang Xinjiang
Published: August 2022

MDM2 and MDM4 proteins are key negative regulators of tumor suppressor p53. MDM2 and MDM4 interact via their RING domains and form a heterodimer polyubiquitin E3 ligase essential for p53 degradation. MDM4 also forms heterodimer E3 ligases with MDM2 isoforms that lack p53-binding domains, which regulate p53 and MDM4 stability. We are working to identify small-molecule inhibitors targeting the RING domain of MDM2-MDM4 (MMRi) that can inactivate the total oncogenic activity of MDM2-MDM4 heterodimers. Here, we describe the identification and characterization of MMRi62 as an MDM4-degrader and apoptosis inducer in leukemia cells. Biochemically, in our experiments, MMRi62 bound to preformed RING domain heterodimers altered the substrate preference toward MDM4 ubiquitination and promoted MDM2-dependent MDM4 degradation in cells. This MDM4-degrader activity of MMRi62 was found to be associated with potent apoptosis induction in leukemia cells. Interestingly, MMRi62 effectively induced apoptosis in p53 mutant, multidrug-resistant leukemia cells and patient samples in addition to p53 wild-type cells. In contrast, MMRi67 as a RING heterodimer disruptor and an enzymatic inhibitor of the MDM2-MDM4 E3 complex lacked MDM4-degrader activity and failed to induce apoptosis in these cells. In summary, this study identifies MMRi62 as a novel MDM2-MDM4-targeting agent and suggests that small molecules capable of promoting MDM4 degradation may be a viable new approach to killing leukemia cells bearing non-functional p53 by apoptosis.
Feasibility and clinical applicability of genomic profiling based on cervical smear samples in patients with endometrial cancer
Authors: Kim Namsoo , Kim Yoo-Na , Lee Kyunglim , Park Eunhyang , Lee Yong Jae , Hwang So Yoon , Park Jihyang , Choi Zisun , Kim Sang Wun , Kim Sunghoon , Choi Jong Rak , Lee Seung-Tae , Lee Jung-Yun
Published: August 2022

Purpose

Cervical smear samples are easily obtainable and may effectively reflect the tumor microenvironment in gynecological cancers. Therefore, we investigated the feasibility of genomic profiling based on tumor DNA analysis from cervical smear samples from endometrial cancer patients.

Materials and methods

Preoperative cervical smear samples were obtained via vaginal sampling in 50 patients, including 39 with endometrial cancer and 11 with benign uterine disease. Matched blood samples were obtained simultaneously. Genomic DNA (gDNA) from cervical smear and/or cell-free DNA from whole blood were extracted and sequenced using the Pan100 panel covering 100 endometrial cancer-related genes.

Results

Cervical swab-based gDNA analysis detected cancer with 67% sensitivity and 100% specificity, showing a superior performance compared to that of the matched blood or Pap smear tests. Cervical swab-based gDNA effectively identified patients with loss of MSH2 or MSH6 and aberrant p53 expression based on immunohistochemistry. Genomic landscape analysis of cervical swab-based gDNA identified PTEN, PIK3CA, TP53, and ARID1A as the most frequently altered genes. Furthermore, 26 endometrial cancer patients could be classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer.

Conclusion

Cervical swab-based gDNA test showed an improved detection potential and allowed the classification of patients, which has both predictive and prognostic implications.
Upregulation of XIAP promotes lung adenocarcinoma brain metastasis by modulating ceRNA network
Authors: Wang Yingjing , Shen Lu , Li Geng , Chen Jiayi , Ge Rong
Published: August 2022

Dysregulation of XIAP has been shown to affect the progression of a variety of cancers, including lung adenocarcinoma (LUAD). However, the function and mechanisms of XIAP in lung adenocarcinoma with brain metastasis (LUAD-BM) remains poorly understood. In this study, we analyzed the differential mRNA of 58 lung adenocarcinomas samples and 28 lung adenocarcinomas with brain metastases in GEO database. 191 differentially expressed mRNAs were significantly associated with immune response, the proliferation of the immune cell, cell-cell adhesion. Subsequent analyzed by lasso and SVM found that XIAP was significantly elevated in LUAD-BM and significantly associated with LUAD grade and metastasis. Then we constructed a molecular regulatory network of ncRNA-miRNA-mRNA ceRNA by Cystoscope based on the correlation obtained from Starbase. It was found that SBF2-AS1 or RUNDC3A-AS1, has-miR-338-3p and XIAP may have a regulatory relationship. Furthermore, we also initially found that XIAP was closely correlation with T cells, B cells, Mast cells, macrophages, and dendritic cells. In conclusion, we found that XIAP was significantly higher expressed in LUAD-BM compared with LUAD without brain metastasis, suggesting that XIAP may play an important role in the future prediction and clinical treatment of LUAD-BM.
Estradiol mediates the interaction of LINC01541 and miR-429 to promote angiogenesis of G1/G2 endometrioid adenocarcinoma in-vitro: A pilot study
Authors: Qiao Dan , Qin Xiaoduo , Yang Haiyan , Liu Xuantong , Liu Libing , Liu Sufen , Jia Zhongzhi
Published: August 2022

Background

Endometrioid adenocarcinoma (EAC) is the most common subtype of endometrial cancer (EC) and is an estrogen-related cancer. In this study, we sought to investigate the expressions and mechanism of action of 17β-estradiol (E2) and long noncoding RNA (lncRNA) LINC01541 in G1/G2 EAC samples.

Methods

The expressions of estrogen receptor β (ESR2), LINC01541, miR-200s, and VEGFA were evaluated using real-time PCR in human EAC tissues (n = 8) and adjacent normal tissues (n = 8). Two EC cell lines (Ishikawa and RL95-2) were selected for validation in vitro. Bioinformatics analyses and luciferase reporter analyses were performed to verify potential binding sites. qRT-PCR, Western blot, and CCK-8 were used to identify the regulatory mechanisms of related genes in cell biological behavior.

Results

Compared with adjacent normal tissues, LINC01541 and miR-200s family (except miR-200c) were highly expressed in EAC tissues (n=8), while ESR2 and VEGFA were lowly expressed in EAC tissues (* P < 0.05; ** P < 0.01). In vitro: E2 inhibited the expression of LINC01541 and miR-429 in both cell lines, and estrogen antagonist (PHTPP) could reverse this effect, in addition, PHTPP could promote the proliferation of these two cancer cells, cell transfection LINC01541 also had this effect after overexpression of plasmid and miR-429 mimic. E2 promotes the expression of VEGFA in both cell lines, and PHTPP can also reverse this effect. LINC01541 interacts with miR-429 to promote the expression of each other, and both inhibit the synthesis of VEGFA in EAC cells after overexpression. Through the double validation of bioinformatics analysis and dual fluorescein reporter gene, it was confirmed that miR-429 targets the regulation of VEGFA expression (* P < 0.05; ** P < 0.01).

Conclusion

E2 promotes the synthesis of VEGFA by altering the expression levels of LINC01541 and miR-429 in EAC, thereby affecting the angiogenesis process of EAC. Also, E2-mediated LINC01541/miR-429 expression may affect cell migration in EAC. In addition, we identified a reciprocal promotion between LINC01541 and miR-429.
Design and Fabrication of a Liver-on-a-chip Reconstructing Tissue-tissue Interfaces
Authors: Liu Jing , Feng Chong , Zhang Min , Song Feng , Liu Haochen
Published: August 2022

Despite the rapid advances in the liver-on-a-chip platforms, it remains a daunting challenge to construct a biomimetic liver-on-a-chip for in vitro research. This study aimed to reconstruct the tissue-tissue interfaces based on bilayer microspheres and form vascularized liver tissue. Firstly, we designed a tri-vascular liver-on-a-chip (TVLOC) comprising a hepatic artery, a portal vein and a central vein, and theoretically analyzed the distribution of velocity and concentration fields in the culture area. Secondly, we designed a bilayer microsphere generating microsystem based on the coaxial confocal principle, which is primarily used to produce bilayer microspheres containing different kinds of cells. Finally, the bilayer microspheres were co-cultured with endothelial cells in the cell culture area of the TVLOC to form vascularized liver tissue, and the cell viability and vascular network growth were analyzed. The results revealed that the TVLOC designed in this study can provide a substance concentration gradient similar to that of the liver microenvironment, and the bilayer microspheres can form a three-dimensional (3D) orderly liver structure with endothelial cells. Such a liver-on-a-chip is capable of maintaining the function of hepatocytes (HCs) pretty well. This work provides full insights into further simulation of the liver-on-a-chip.
Role of intraoperative patients positioning in endoscopic full-thickness resection of large gastric tumors under general anesthesia
Authors: Zhou Li-Jun , Xing Fei , Chen Dan , Li Yan-Na , Rafiq Shoaib Mohammad
Published: August 2022

Full thickness endoscopic resection of large submucosal gastric tumors (>3 cm) is a big challenge for endoscopists. Issues include how to efficiently resect the lesion, obtain homeostasis, and suture the defect. There are no guidelines regarding the importance of patient position on the success of endoscopic resections in anesthetized patients. Typically, the patient is placed in left lateral position for the endoscopic therapy and during the procedure patient’s position is changed to maintain the tumor above the gastric fluids to prevent gastric juices and tumor or tumor fragments from falling into the peritoneal cavity in the event of perforation. This study emphasized the importance of planning the procedure to ensure that the patient’s position and anesthetist’s concerns are met and allow optimal access to the lesion for endoscopic resection. Prior to sedation the patient should be positioned so that the tumor is in the up position which also prevents blood obscuring the operative field, helps detect bleeding points for immediately hemostasis. In addition, due to gravitational effect, the resected tumor will fall into the gastric cavity exposing the root of the tumor making resection easier and reduce procedure time. Preplanning avoids unnecessary readjustment of positioning and improves the ease and safety of the procedure.
Paclitaxel-incorporated nanoparticles improve functional recovery after spinal cord injury
Authors: Zhang Xinzhu , Xiong Wu , Kong Guang , Zhen Yushan , Zeng Qiang , Wang Siming , Chen Sheng , Gu Jun , Li Cong , Guo Kaijin
Published: August 2022

As a worldwide medical problem, spinal cord injury has no clear and effective treatment to improve its prognosis. Hence, new treatment strategies for spinal cord injury with good therapeutic efficacy have been actively pursued. As a new drug loading system, acetal dextran nanoparticles (SAD) have good biocompatibility and biodegradability. Therefore, we designed spermine-functionalized acetal-dextran (SAD) nanoparticles and encapsulated paclitaxel (PCL) into them. This design can ensure the sustained release of paclitaxel in the injured area for 4 days and promote the extension of nerve processes in vitro. In our experiment, we found that paclitaxel-loaded SAD nanoparticles (PCL@SAD) decreased the level of chondroitin sulfate proteoglycan in the rat spinal cord injury model, which reduced the scar repair of the injured site and changed the inhibitory environment after spinal cord injury. This reveals that PCL@SAD can effectively protect the injured spinal cord and ultimately improve the functional recovery of the injured spinal cord. One single injection of PCL@SAD shows better therapeutic effect than that of PCL. This study opens an exciting perspective toward the application of neuroprotective PCL@SAD for the treatment of severe neurological diseases.
The new challenge of “exercise + X″ therapy for Duchenne muscular dystrophy—Individualized identification of exercise tolerance and precise implementation of exercise intervention
Authors: Su Yuhui , Song Yafeng
Published: August 2022

Duchenne muscular dystrophy (DMD) is an X-linked recessive fatal muscular disease. Gene therapy, cell therapy, and drug therapy are currently the most widely used treatments for DMD. However, many experiments on animals and humans suggested that appropriate exercise could improve the effectiveness of such precision medicine treatment, thereby improving patient’s muscle quality and function. Due to the striated muscle damage of DMD individuals, there are still many debates about whether DMD animals or patients can exercise, how to exercise, when to exercise best, and how to exercise effectively. The purpose of this review is to summarize and investigate the scientific basis and efficacy of exercise as an adjuvant therapy for DMD gene therapy, cell therapy and drug therapy, as well as to present the theoretical framework and optional strategies of “exercise + X″″ combination therapy.
The effect of Azorhizobium caulinodans ORS571 and γ-aminobutyric acid on salt tolerance of Sesbania rostrata
Authors: Liu Yanan , Liu Xiaolin , Dong Xiaoyan , Yan Jiaming , Xie Zhihong , Luo Yongming
Published: August 2022

Salt stress seriously affects plant growth and crop yield, and has become an important factor that threatens the soil quality worldwide. In recent years, the cultivation of salt-tolerant plants such as Sesbania rostrata has a positive effect on improving coastal saline-alkali land. Microbial inoculation and GABA addition have been shown to enhance the plant tolerance in response to the abiotic stresses, but studies in green manure crops and the revelation of related mechanisms are not clear. In this study, the effects of inoculation with Azorhizobium caulinodans ORS571 and exogenous addition of γ-Aminobutyric Acid (GABA; 200 mg·L−1) on the growth and development of S. rostrata under salt stress were investigated using potting experiments of vermiculite. The results showed that inoculation with ORS571 significantly increased the plant height, biomass, chlorophyll content, proline content (PRO), catalase (CAT) activity, and superoxide dismutase (SOD) activity of S. rostrata and reduced the malondialdehyde (MDA) level of leaves. The exogenous addition of GABA also increased the height, biomass, and CAT activity and reduced the MDA and PRO level of leaves. In addition, exogenous addition of GABA still had a certain improvement on the CAT activity and chlorophyll content of the ORS571-S. rostrata symbiotic system. In conclusion, ORS571 inoculation and GABA application have a positive effect on improving the salt stress tolerance in S. rostrata, which are closely associated with increasing chlorophyll synthesis and antioxidant enzyme activity and changing the amino acid content. Therefore, it can be used as a potential biological measure to improve the saline-alkali land.
Hairy roots: An untapped potential for production of plant products
Authors: Morey Kevin J. , Peebles Christie A. M.
Published: August 2022

While plants are an abundant source of valuable natural products, it is often challenging to produce those products for commercial application. Often organic synthesis is too expensive for a viable commercial product and the biosynthetic pathways are often so complex that transferring them to a microorganism is not trivial or feasible. For plants not suited to agricultural production of natural products, hairy root cultures offer an attractive option for a production platform which offers genetic and biochemical stability, fast growth, and a hormone free culture media. Advances in metabolic engineering and synthetic biology tools to engineer hairy roots along with bioreactor technology is to a point where commercial application of the technology will soon be realized. We discuss different applications of hairy roots. We also use a case study of the advancements in understanding of the terpenoid indole alkaloid pathway in Catharanthus roseus hairy roots to illustrate the advancements and challenges in pathway discovery and in pathway engineering.
Induced variations of ethyl methane sulfonate mutagenized cowpea (Vigna unguiculata L. walp) plants
Authors: Opoku Gyamfi Muhammed , Eleblu John Saviour Yaw , Sarfoa Lawrencia Gyamfi , Asante Isaac Kojo , Opoku-Agyemang Frank , Danquah Eric Yirenkyi
Published: August 2022

Unique variants are desired in the development of genetically improved crops to meet farmer and market needs hence ethyl methane sulfonate (EMS) was used to induce genetic variability in cowpea (Vigna unguiculata cv. Asontem). The main objective of this research was to characterize induced variations in EMS chemically mutagenized population of cowpea (Vigna unguiculata L. Walp Var. Asontem) in the M1 and M2 generations. The optimum concentration (LD50) of EMS for generating the mutagenized population was determined by treating seeds with different concentrations of EMS (0.0, 0.2, 0.4, 0.6, and 0.8% v/v) and observing the germination count after 5 days of planting the seeds in Petri dishes. Three thousand cowpea seeds were treated with the 0.4% EMS to generate the M1 and M2 populations that were evaluated for agronomic and morphological traits with untreated seeds serving as control. Data analysis involved distribution of qualitative and quantitative traits. Germination was significantly reduced in the mutagenized population (17.8%) and compared with that of the wild type (61.6%). Percentage survival was significantly higher in wild type (98.38%) as compared with the M1 population (78.46%). Percentage germination in the M2 population (74.03%) was lower than the wild type (80%). A wide spectrum of agro-morphological abnormalities was observed in the M2 population. Wide variations and uniquely different phenotypic classes were observed in leaf color, leaf shape, growth habit, plant pigmentation, twining tendency, pod curvature, seed shape, and seed coat color. M2 individuals were widely distributed for days to flowering, number of pods per plant, number of seeds per pod, number of locules per pods, percentage seed set, pod length and number of seeds per plant. In conclusion, the EMS mutagenesis was effective in inducing the unique variations that will be useful for breeding and development of new farmer preferred varieties.
Epigenetics at the crossroads of secondary growth regulation
Authors: Inácio Vera , Santos Raquel , Prazeres Rafael , Graça José , Miguel Célia M. , Morais-Cecílio Leonor
Published: August 2022

The development of plant tissues and organs during post-embryonic growth occurs through the activity of both primary and secondary meristems. While primary meristems (root and shoot apical meristems) promote axial plant growth, secondary meristems (vascular and cork cambium or phellogen) promote radial thickening and plant axes strengthening. The vascular cambium forms the secondary xylem and phloem, whereas the cork cambium gives rise to the periderm that envelops stems and roots. Periderm takes on an increasingly important role in plant survival under climate change scenarios, but it is also a forest product with unique features, constituting the basis of a sustainable and profitable cork industry. There is established evidence that epigenetic mechanisms involving histone post-translational modifications, DNA methylation, and small RNAs play important roles in the activity of primary meristem cells, their maintenance, and differentiation of progeny cells. Here, we review the current knowledge on the epigenetic regulation of secondary meristems, particularly focusing on the phellogen activity. We also discuss the possible involvement of DNA methylation in the regulation of periderm contrasting phenotypes, given the potential impact of translating this knowledge into innovative breeding programs.
International migration and the rise of urban militant networks in the Mediterranean
Authors: Lacroix Thomas , Furri Filippo , Hombert Louise
Published: August 2022

From the US to Italy, from Brazil to Japan, cities from all over the world are increasingly vocal on migration issues. Advocating for alternative approach to immigrants' welcome, their stand and policies may at times be in blunt contradiction with national approaches. This paper gives an overview of this new form of urban militancy, its recent evolution, its forms, its networks. Drawing on case studies in France, Spain and Italy, it seeks to explain why the Mediterranean has been an important setting for the politicization of municipal involvement and the rise of multi-actor power assemblage of municipalities and voluntary organizations.
Can the word superiority effect be modulated by serial position and prosodic structure?
Authors: Marzouki Yousri , Al-Otaibi Sara Abdulaziz , Al-Tamimi Muneera Tariq , Idrissi Ali
Published: August 2022

In this study, we examined the word superiority effect in Arabic and English, two languages with significantly different morphological and writing systems. Thirty-two Arabic–English bilingual speakers performed a post-cued letter-in-string identification task in words, pseudo-words, and non-words. The results established the presence of the word superiority effect in Arabic and a robust effect of context in both languages. However, they revealed that, compared to the non-word context, word and pseudo-word contexts facilitated letter identification more in Arabic than in English. In addition, the difference between word and pseudo-word contexts was smaller in Arabic compared to English. Finally, there was a consistent first-letter advantage in English regardless of the context, while this was more consistent only in the word and pseudo-word contexts in Arabic. We discuss these results in light of previous findings and argue that the differences between the patterns reported for Arabic and English are due to the qualitative difference between word morphophonological representations in the two languages.
The brain dynamics of trust decisions and outcome evaluation in narcissists
Authors: Guo Fengbo , Yang Ziyang , Liu Tengfei , Gu Li
Published: August 2022

Individuals with narcissism are, by definition, self-centered, focus on self-benefit, and demonstrate less prosocial behaviors. Trusting strangers is risky, as it can result in exploitation and non-reciprocation. Thus, the trust may be antagonistic to narcissism. However, how narcissists make the choice to trust remains to be elucidated. The current study examined 44 participants (22 rated high in narcissism) playing as trustors in one-shot trust games, and their electroencephalograms were recorded. Individuals high in narcissism exhibited less trust toward strangers, especially following gaining feedback for their trust. In addition, narcissists exhibited a larger N2 following distrust and a stronger negatively-valanced difference in feedback-related negativity (dFRN) after trustee feedback. Our findings provide insights into how individuals with narcissism trust strangers. The results also shed light on the temporal course of brain activity involved in trust decision-making and outcome evaluation in individuals with narcissism.
Quantitative ESG disclosure and divergence of ESG ratings
Authors: Liu Min
Published: August 2022

Over the past decade, sustainable finance has been a topic of burgeoning significance for investors, and ESG ratings have become commonly used to implement ESG investment strategies in practice. Strikingly, it is widely documented in both academic literature and investment practices that ESG ratings of a given firm can be extremely different across rating providers. However, despite the disagreement in ESG ratings being subject to a lot of criticism, only few studies have examined the sources and determinants of rating divergence. This study examines whether quantitative ESG disclosure is conducive to rating convergence among agencies. Based on ESG rating data of Chinese A-share listed companies, the author finds that greater quantitative ESG disclosure, especially disclosure on environmental and social pillars, results in greater divergence of ESG ratings. When employing a difference-in-differences design with a quasi-experiment of disclosure guidance introduced by Hong Kong Exchange, the results show that if ESG disclosure is standardized and comparable, more numerical information reduces agencies' rating disagreement instead. Further analyses show that the lack of agreement is related to a low rating in the future. The author also finds that the effect of quantified ESG disclosure on rating divergence is more pronounced when firms are single businesses rather than diversified businesses with poor ESG performance rather than good ESG performance. The results are robust to alternative measures of ESG rating divergence, alternative sample, two-way clustering, and additional control variables. Taken together, the results indicate that quantitative ESG disclosure degenerates rating disagreement.
“I'm in pain and I want help”: An online survey investigating the experiences of tic-related pain and use of pain management techniques in people with tics and tic disorders
Authors: Taylor Evangeline , Anderson Seonaid , Davies E. Bethan
Published: August 2022

Objectives

Tic disorders (TDs) are complex neurological conditions characterized by involuntary, persistent vocalizations and motor movements called tics. Tics involve brief muscle movements and can impair many aspects of daily functioning and quality of life in patients – and their physical nature can cause pain. Understanding individuals' experiences of tic-related pain and pain management could help explore this under-researched area and identify additional support needs for this population. The aim of this study was to investigate experiences of pain and use of pain management techniques in people with tic disorders.

Methods

An online survey consisting of multiple choice and open-ended questions exploring experiences of tic-related pain, help-seeking behavior for tic-related pain, and use of pain relief techniques for tic-related pain, was circulated onlineviainternational Tourette syndrome patient associations, and one online support group for Tourette syndrome. The online survey was open to adults (≥16 years) with self-reported tics. Open-ended questions were analyzed using thematic analysis.

Results

One hundred eighty-one participants (16–71 years; 58.0% female) from 18 countries completed the online survey. Several aspects of tics were associated with pain, including the physical effort of motor tics (n= 177, 97.8%), repetitive tics (n= 141, 77.9%) and the consequences of tics (n= 131, 72.4%). Nearly two-thirds (n= 118, 64.6%) had sought professional help for tic-related pain. Distraction techniques (n= 126, 69.6%), taking pain relief medication (n= 125, 69.1%) and altering tics (n= 111, 61.3%) were the most commonly-reported methods used to relieve and cope with tic-related pain. Thematic analysis found an interrelated complex relationship between participants' tics, pain, and pain management techniques, reflected in four themes: the “tic-pain” cycle, the impact of pain, the importance of support, and the perceived successfulness of pain management techniques.

Conclusions

Tic-related pain was reported to have a significant physical and psychological impact which impacted aspects of daily living in people with tic disorders. The findings add to limited research suggesting tic-related pain is a dominant issue for individuals with tic disorders, potentially impacting upon their quality of life. Increased understanding of tic-related pain and its influence may be helpful in the long-term management of tic disorders, both in terms of clinical management and patients' self-management.
Effects of coronavirus disease 2019 lockdown on metabolic syndrome and its components among Chinese employees: A retrospective cohort study
Authors: Xu Weiwei , Li Yujuan , Yan Yixin , Zhang Liyun , Zhang Junhui , Yang Chao
Published: August 2022

Objective

Coronavirus disease 2019 (COVID-19) and the accompanying isolation have changed resident life rhythms and behaviors. This study investigated the effects of the COVID-19 pandemic on metabolic syndrome (MetS) and its components in employees in southwestern China.

Methods

This retrospective cohort study included 3,777 employees of five institutions who underwent physical examinations at the Affiliated Hospital of Southwest Medical University for three consecutive years from 2018 to 2020. We collected data on participant age and sex and measured the component indices of metabolic syndrome, including waist circumference, blood pressure (systolic and diastolic), fasting blood glucose level, and blood lipid (triglyceride and high-density lipoprotein cholesterol) level. We applied t-, chi-square, Mann–Whitney U, and Friedman's M tests to compare metabolic variables at different times.

Results

The incidence of MetS in 2020 was 18.6%, significantly higher than the prevalence of 15.7% before the epidemic. The number of abnormal MetS components following the COVID-19 lockdown was much greater than those in 2018 (P < 0.001) and 2019 (P < 0.001), with no significant variations between the two years (P = 0.142). All metabolic parameters, except for fasting blood glucose, were significantly worse than those pre-lockdown. The increase in the prevalence of MetS and all its abnormal components except for fasting glucose from 2019 to 2020 was significantly higher than that from 2018 to 2019. The change values between 2019–2020 and 2018–2019 for all indices except for diastolic blood pressure did not differ significantly between men and women. For all component indicators except for waist circumference, we observed no significant age differences in the growth differentials between the two periods (2019–2020 and 2018–2019).

Conclusions

COVD-19 lockdown have increased metabolic health risks among Chinese adults. Targeted measures, such as health education, are urgently needed to address poor metabolic health caused by the COVID-19 pandemic.
Perceived effect of warning label on parental food purchasing and drivers of food selection among South African parents–An exploratory study
Authors: Bopape Makoma , Taillie Lindsey Smith , Swart Rina
Published: August 2022

Household food purchasing decision is a complex process influenced by factors such as marketing, cost, children food preference and parental choices. Most food products targeted toward children are unhealthy and are aggressively marketed to increase desirability among parents and children making healthier food selection even harder. The warning label (WL) is identified as a simple front-of-package labeling format that assist consumers to easily identify unhealthy foods and reduce their purchasing. This was a qualitative study that aimed to investigate the perceived effect of the warning label (WL) on parental food purchasing and drivers of food selection among parents. The study was conducted in a mainly rural part of South Africa, in Limpopo Province. Data were collected from 44 adult participants, all parents with children aged below 16 years selected using the snowball sampling method. Seven focus groups diversified according to age, literacy, income and urbanicity were utilized for data collection. Using a focus group discussion guide, parents were shown images of six products (crisps, soda, juice, biscuits, cereals, and yogurt) superimposed with the WL and questions asked were based on those images. Thematic analysis revealed that although some parents felt undeterred by the WL, some felt they would alter their food purchasing in the presence of the WL. Other parents felt they would reduce the frequency or the amount purchased or completely stop purchasing labeled products for their children. Motives behind perceived behavior modification included children's health being perceived as a priority and labeled products being viewed as unhealthy. Factors such as pressure from children, taste, poor nutrition knowledge and affordability seemed to influence parental food selection. These findings have important policy implications by providing evidence to policymakers that the WL may alter parental food purchasing and also provide insight into drivers of food selection among South African parents.
COVID-19 diagnosis using deep learning neural networks applied to CT images
Authors: Akinyelu Andronicus A. , Blignaut Pieter
Published: August 2022

COVID-19, a deadly and highly contagious virus, caused the deaths of millions of individuals around the world. Early detection of the virus can reduce the virus transmission and fatality rate. Many deep learning (DL) based COVID-19 detection methods have been proposed, but most are trained on either small, incomplete, noisy, or imbalanced datasets. Many are also trained on a small number of COVID-19 samples. This study tackles these concerns by introducing DL-based solutions for COVID-19 diagnosis using computerized tomography (CT) images and 12 cutting-edge DL pre-trained models with acceptable Top-1 accuracy. All the models are trained on 9,000 COVID-19 samples and 5,000 normal images, which is higher than the COVID-19 images used in most studies. In addition, while most of the research used X-ray images for training, this study used CT images. CT scans capture blood arteries, bones, and soft tissues more effectively than X-Ray. The proposed techniques were evaluated, and the results show that NASNetLarge produced the best classification accuracy, followed by InceptionResNetV2 and DenseNet169. The three models achieved an accuracy of 99.86, 99.79, and 99.71%, respectively. Moreover, DenseNet121 and VGG16 achieved the best sensitivity, while InceptionV3 and InceptionResNetV2 achieved the best specificity. DenseNet121 and VGG16 attained a sensitivity of 99.94%, while InceptionV3 and InceptionResNetV2 achieved a specificity of 100%. The models are compared to those designed in three existing studies, and they produce better results. The results show that deep neural networks have the potential for computer-assisted COVID-19 diagnosis. We hope this study will be valuable in improving the decisions and accuracy of medical practitioners when diagnosing COVID-19. This study will assist future researchers in minimizing the repetition of analysis and identifying the ideal network for their tasks.
Investigating the relationship between cancer and orofacial clefts using GWAS significant loci for cancers: A case-control and case-triad study
Authors: Fashina Azeez , Busch Tamara , Young Mary , Adamson Olawale , Awotoye Waheed , Alade Azeez , Adeleke Chinyere , Hassan Mohaned , Oladayo Abimbola M. , Gowans Lord J. J. , Eshete Mekonen , Naicker Thirona , Olotu Joy , Adeyemo Wasiu L. , Butali Azeez
Published: August 2022

Background

Several population-based case-control studies have reported concurrent presentation of cancer and congenital malformations. Many associations have been made between oral clefting and cancers, though some of these results are conflicting. Some studies have reported an increased risk of cancer among 1st-degree relatives of cleft cases and vice versa, and also an excess risk of cancers of the breast, lung, and brain among those with oral clefts. This study aimed to determine if the genetic polymorphisms found in some cancers are also associated with orofacial cleft in an African cohort.

Methods

The study was a case-control and case-triad study in which cases were 400 individuals clinically diagnosed with non-syndromic cleft lip and/or palate (CL/P), while controls were 450 individuals without CL/P. Samples were obtained from three African countries while DNA extraction, PCR, and genotyping were carried out at the University of Iowa, US. Eleven SNPs in genes coding for SWI/SNF subunits and 13 GWAS significant SNPs for cancers associated with orofacial cleft were selected. Case-control analysis, transmission disequilibrium test (TDT), and DFAM to combine the parent-offspring trio data and unrelated case/control data in a single analysis were carried out using PLINK.

Results

For the case-control analyses that included all the clefts and for the CLP subtype, none of the SNPs were statistically significant. Statistically increased risk for the following SNPs rs34775372 (p = 0.02; OR = 1.54, CI:1.07–2.22), rs55658222 (p = 0.009; OR = 2.64, CI:1.28–5.45) and rs72728755 (p = 0.02; OR=2.27, CI:1.17–4.45) was observed with the CL only sub-group. None of these were significant after Bonferoni correction. In the TDT analyses, a significantly reduced risk with rs10941679 (p = 0.003; OR = 0.43, CI:0.24–0.75) was observed and this was significant after Bonferroni correction. The rs10941679 was also significant (p = 0.003) in the DFAM analyses as well even after Bonferroni correction.

Conclusion

The results from this study represent an important starting point for understanding the concurrent presentation of some cancers in orofacial clefts, and cancer risks in cleft patients. The associations observed warrant further investigation in a larger cohort and will set the stage for a more mechanistic approach toward understanding the risk for cancers in families with clefts.