bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomic Alterations in Multiple Myeloma: A Comprehensive Study Using Bone Marrow Interstitial Fluid and Serum Samples
Authors: Chanukuppa Venkatesh , Taware Ravindra , Taunk Khushman , Chatterjee Tathagat , Sharma Sanjeevan , Somasundaram Venkatesan , Rashid Faraz , Malakar Dipankar , Santra Manas K. , Rapole Srikanth
Published: January 2021

Multiple myeloma (MM) is a plasma cell-associated cancer and exists as the second most common hematological malignancy worldwide. Although researchers have been working on MM, a comprehensive quantitative Bone Marrow Interstitial Fluid (BMIF) and serum proteomic analysis from the same patients’ samples is not yet reported. The present study involves the investigation of alterations in the BMIF and serum proteome of MM patients compared to controls using multipronged quantitative proteomic approaches viz., 2D-DIGE, iTRAQ, and SWATH-MS. A total of 279 non-redundant statistically significant differentially abundant proteins were identified by the combination of three proteomic approaches in MM BMIF, while in the case of serum 116 such differentially abundant proteins were identified. The biological context of these dysregulated proteins was deciphered using various bioinformatic tools. Verification experiments were performed in a fresh independent cohort of samples using immunoblotting and mass spectrometry based SRM assays. Thorough data evaluation led to the identification of a panel of five proteins viz., haptoglobin, kininogen 1, transferrin, and apolipoprotein A1 along with albumin that was validated using ELISA in a larger cohort of serum samples. This panel of proteins could serve as a useful tool in the diagnosis and understanding of the pathophysiology of MM in the future.
Next-Generation Sequencing of DDX41 in Myeloid Neoplasms Leads to Increased Detection of Germline Alterations
Authors: Bannon Sarah A. , Routbort Mark J. , Montalban-Bravo Guillermo , Mehta Rohtesh S. , Jelloul Fatima Zahra , Takahashi Koichi , Daver Naval , Oran Betul , Pemmaraju Naveen , Borthakur Gautam , Naqvi Kiran , Issa Ghayas , Sasaki Koji , Alvarado Yesid , Kadia Tapan M. , Konopleva Marina , Shamanna Rashmi Kanagal , Khoury Joseph D. , Ravandi Farhad , Champlin Richard , Kantarjian Hagop M. , Bhalla Kapil , Garcia-Manero Guillermo , Patel Keyur P. , DiNardo Courtney D.
Published: January 2021

Previously considered rare, inherited hematologic malignancies are increasingly identified. Germline mutations in the RNA helicase DDX41 predispose to increased lifetime risks of myeloid neoplasms with disease often occurring later in life which presents challenges for germline recognition. To improve identification of germline DDX41, individuals presenting with ≥1 DDX41 alteration on an institutional MDS/AML next-generation sequencing based panel with at least one at >40% variant allele frequency were flagged for review and genetic counseling referral. Of 5,801 individuals, 90 (1.5%) had ≥1 DDX41 mutation(s) identified. Thirty-eight (42%) patients with a median age of 66 years were referred for genetic counseling; thirty-one were male (81.5%). Thirty-five (92%) referred patients elected to pursue germline evaluation and in 33/35 (94%) a germline DDX41 variant was confirmed. Twenty-two patients (66%) with germline variants reported antecedent cytopenias, seven (21%) had a prior history of malignancy, and twenty-seven (82%) reported a family history of cancer. Predictive genetic testing for healthy family members under consideration as stem cell transplant donors was successfully performed in 11 family members, taking an average of 15 days. Near-heterozygous DDX41 mutations identified on next-generation sequencing, particularly nonsense/frameshift variants or those at recurrent germline “hot spots” are highly suggestive of a germline mutation. Next-generation sequencing screening is a feasible tool to screen unselected myeloid neoplasms for germline DDX41 mutations, enabling timely and appropriate care.
Antioxidant-Rich Diet, GSTP1 rs1871042 Polymorphism, and Gastric Cancer Risk in a Hospital-Based Case-Control Study
Authors: Kim Jimi , Kim Hyejin , Lee Jeonghee , Choi Il Ju , Kim Young-Il , Kim Jeongseon
Published: January 2021

Background

Chronic gastritis along with Helicobacter pylori (H. pylori) infection has been implicated in inflammatory response-related genes linked to the causation of gastric cancer. Glutathione S-transferase Pi (GSTP1) plays a role in regulating oxidative stress and detoxification against carcinogenesis. In this study, we aimed to determine whether an antioxidant-rich diet is associated with gastric cancer risk and identify how this association could be altered by GSTP1 genetic variants.

Methods

This study included 1,245 participants (415 cases and 830 controls) matched for age and sex. The dietary antioxidant capacity was estimated based on the oxygen radical absorbance capacity (ORAC) incorporated with a semiquantitative food frequency questionnaire. Five single nucleotide polymorphisms (SNPs) of GSTP1 (rs1695, rs749174, rs1871042, rs4891, and rs947895) were selected among the exome array genotype data.

Results

High dietary ORAC was inversely associated with gastric cancer (hydrophilic ORAC OR T3vs. T1, 95% CI = 0.57, 0.39–0.82, P = 0.004; lipophilic ORAC = 0.66, 0.45–0.95, P = 0.021; total phenolics = 0.57, 0.39–0.83, P = 0.005). The polymorphism rs1871042 increased the risk of gastric cancer (OR, 95% CI = 1.55, 1.10–2.16, P = 0.01, CT+TT vs. CC). A remarkably reduced risk of gastric cancer was observed among those who had a high dietary ORAC according to rs1871042 polymorphism (hydrophilic ORAC OR T3vs. T1, 95% CI = 0.36, 0.17–0.78, P for trend = 0.013; lipophilic ORAC = 0.58, 0.37–0.93, P for trend = 0.021; total phenolics = 0.38, 0.17–0.83, P for trend = 0.019).

Conclusions

Our findings indicate that dietary ORAC intake may be inversely associated with the risk of gastric cancer altered by genetic variants of GSTP1, providing new intervention strategies for gastric cancer patients.
Evolution of Experimental Models in the Study of Glioblastoma: Toward Finding Efficient Treatments
Authors: Gómez-Oliva Ricardo , Domínguez-García Samuel , Carrascal Livia , Abalos-Martínez Jessica , Pardillo-Díaz Ricardo , Verástegui Cristina , Castro Carmen , Nunez-Abades Pedro , Geribaldi-Doldán Noelia
Published: January 2021

Glioblastoma (GBM) is the most common form of brain tumor characterized by its resistance to conventional therapies, including temozolomide, the most widely used chemotherapeutic agent in the treatment of GBM. Within the tumor, the presence of glioma stem cells (GSC) seems to be the reason for drug resistance. The discovery of GSC has boosted the search for new experimental models to study GBM, which allow the development of new GBM treatments targeting these cells. In here, we describe different strategies currently in use to study GBM. Initial GBM investigations were focused in the development of xenograft assays. Thereafter, techniques advanced to dissociate tumor cells into single-cell suspensions, which generate aggregates referred to as neurospheres, thus facilitating their selective expansion. Concomitantly, the finding of genes involved in the initiation and progression of GBM tumors, led to the generation of mice models for the GBM. The latest advances have been the use of GBM organoids or 3D-bioprinted mini-brains. 3D bio-printing mimics tissue cytoarchitecture by combining different types of cells interacting with each other and with extracellular matrix components. These in vivo models faithfully replicate human diseases in which the effect of new drugs can easily be tested. Based on recent data from human glioblastoma, this review critically evaluates the different experimental models used in the study of GB, including cell cultures, mouse models, brain organoids, and 3D bioprinting focusing in the advantages and disadvantages of each approach to understand the mechanisms involved in the progression and treatment response of this devastating disease.
Overexpression of LncRNA BM466146 Predicts Better Prognosis of Breast Cancer
Authors: Zhang Yunxiang , Dong Xiaotong , Wang Yang , Wang Liquan , Han Guiyan , Jin Lvcheng , Fan Yanping , Xu Guodong , Yuan Dawei , Zheng Jie , Guo Xiangyu , Gao Peng
Published: January 2021

This study analyzes the expression and clinical significance of long non-coding RNA (lncRNA) BM466146 in breast cancer, and explores the role of BM466146 in immune regulation. The expression of BM466146 in 89 cases of breast cancer and their corresponding non-cancerous breast tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier survival analysis was applied to evaluate patient survival. EDU and CCK-8 experiments on breast cancer cells were performed to verify the function of BM466146 in vitro. The target genes of BM466146 were screened by informatics analysis to predict associated miRNAs and their corresponding mRNAs, immune genes associated with lncRNAs and chemokines associated with CD8. Immunohistochemistry was used to detect the expression of CD8, Ki-67, and CXCL-13 in the 89 breast cancer tissues. It was found that the expression of lncRNA BM466146 in breast cancer tissues was significantly lower than that in normal breast tissues (P < 0.001). In breast cancer, tissues that overexpressed BM466146 exhibited a lower Ki-67 index compared with that of low BM466146 expression (P = 0.048). Kaplan-Meier survival analysis showed that breast cancer patients with overexpression of BM466146 had longer overall survival. EDU and CCK8 experiments showed that overexpression of BM466146 inhibited the proliferation of breast cancer cells. The hsa-miR-224-3p is associated with BM466146, and its target gene might be CXCL-13. The positive CD8 cells in the BM466146 overexpression group was higher than that in the low BM466146 expression group (P=0.027), and the positive CD8 cells in the CXCL-13 positive group was higher (P=0.023) than that of the negative group. Our results indicate that the lncRNA BM466146 has the function of tumor suppressor gene. Overexpression of BM466146 is associated with better prognosis. BM466146 could regulate CXCL-13 by adsorbing hsa-miR-224-3p and inducing CD8+ T cells to accumulate in the tumor area which regulate immune response. Therefore, BM466146 could be a prognostic biomarker and a molecular immune target of breast cancer.
Comparison Between Urothelial and Non-Urothelial Urethral Cancer
Authors: Wenzel Mike , Deuker Marina , Nocera Luigi , Collà Ruvolo Claudia , Tian Zhe , Shariat Shahrokh F. , Saad Fred , Briganti Alberto , Becker Andreas , Kluth Luis A. , Chun Felix K.H. , Karakiewicz Pierre I.
Published: January 2021

Background

To test the effect of variant histology relative to urothelial histology on stage at presentation, cancer specific mortality (CSM), and overall mortality (OM) after chemotherapy use, in urethral cancer.

Materials and Methods

Within the Surveillance, Epidemiology and End Results (2004–2016) database, we identified 1,907 primary variant histology urethral cancer patients. Kaplan-Meier plots, Cox regression analyses, cumulative incidence-plots, multivariable competing-risks regression models and propensity score matching for patient and tumor characteristics were used.

Results

Of 1,907 eligible urethral cancer patients, urothelial histology affected 1,009 (52.9%) vs. squamous cell carcinoma (SCC) 455 (23.6%) vs. adenocarcinoma 278 (14.6%) vs. other histology 165 (8.7%) patients. Urothelial histological patients exhibited lower stages at presentation than SCC, adenocarcinoma or other histology patients. In urothelial histology patients, five-year CSM was 23.5% vs. 34.4% in SCC [Hazard Ratio (HR) 1.57] vs. 40.7% in adenocarcinoma (HR 1.69) vs. 43.4% in other histology (HR 1.99, p < 0.001). After matching in multivariate competing-risks regression models, variant histology exhibited 1.35-fold higher CSM than urothelial. Finally, in metastatic urethral cancer, lower OM was recorded after chemotherapy in general, including metastatic adenocarcinoma and other variant histology subtypes, except metastatic SCC.

Conclusion

Adenocarcinoma, SCC and other histology subtypes affect fewer patients than urothelial histology. Presence of variant histology results in higher CSM. Finally, chemotherapy for metastatic urethral cancer improves survival in adenocarcinoma and other variant histology subtypes, but not in SCC.
Protective Effects of Pterostilbene on Lipopolysaccharide-Induced Acute Lung Injury in Mice by Inhibiting NF-κB and Activating Nrf2/HO-1 Signaling Pathways
Authors: Zhang Yong , Han Zhen , Jiang Aimin , Wu Di , Li Shuangqiu , Liu Ziyi , Wei Zhengkai , Yang Zhengtao , Guo Changming
Published: January 2021

Pterostilbene (PTER) is a kind of stilbene compound with biological activity isolated from plants such as red sandalwood, blueberry and grape. It has anti-tumor, anti-bacterial, anti-oxidation and other pharmacological activities. However, the underlying mechanism of the protective effect of PTER on lipopolysaccharide (LPS)-induced acute lung injury (ALI) remained not clarified. In this study, LPS was used to establish a mouse model of ALI. Bronchoalveolar lavage fluid (BALF) was collected for inflammatory cells, and the wet-to-dry weight ratio of the lungs was measured. The activities of myeloperoxidase (MPO), antioxidant indexes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and oxidation index such as malondialdehyde (MDA) in lung tissues of mice were measured by the corresponding kits. The levels of Cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), TNF-α, IL-6 and IL-1β in lung tissues of mice were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The activities of Nrf2, HO-1, p-p65 and p-IκB were determined by western blotting. The results showed that the model of LPS-induced ALI was successfully replicated, and it was found that PTER could significantly improve the pathological degree of ALI such as sustained the integrity of the lung tissue structure, alleviated pulmonary interstitial edema and alveolar wall thickening, reduced infiltrated inflammatory cells. PTER could decrease the number of inflammatory cells and obviously inhibit the increase of W/D ratio caused by LPS. PTER could also significantly reduce LPS-induced MPO and MDA, and increase LPS-decreased SOD, CAT and GSH-Px in the lungs. In addition, it was also found that PTER has the ability to decrease LPS-induced production of COX-2, iNOS, TNF-α, IL-6 and IL-1β. The underlying mechanism involved in the protective effect of PTER on ALI were via activating Nrf2 and HO-1, and inhibiting the phosphorylation of p65 and IκB. These results suggested that PTER can protect LPS-induced ALI in mice by inhibiting inflammatory response and oxidative stress, which provided evidence that PTER may be a potential therapeutic candidate for LPS-induced ALI intervention.
Perspectives of Antidiabetic Drugs in Diabetes With Coronavirus Infections
Authors: Sun Bao , Huang Shiqiong , Zhou Jiecan
Published: January 2021

Diabetes mellitus (DM) increases the risk of viral infections especially during the period of poor glycemic controls. Emerging evidence has reported that DM is one of the most common comorbidities in the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, also referred to as COVID-19. Moreover, the management and therapy are complex for individuals with diabetes who are acutely unwell with suspected or confirmed COVID-19. Here, we review the role of antidiabetic agents, mainly including insulin, metformin, pioglitazone, dipeptidyl peptidase-4 (DPP4) inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists in DM patients with coronavirus infection, addressing the clinical therapeutic choices for these subjects.
Resistance of Food-Maintained Operant Responding to Mechanical Punishment in Rats: Further Evidence for Weak “Affective/Motivational Pain” in Rat Models of Inflammatory and Neuropathic Pain
Authors: Negus S. Stevens , Marsh S. A. , Townsend E. A.
Published: January 2021

Clinically relevant chronic pain is often associated with functional impairment and behavioral depression as an “affective/motivational” sign of pain; however preclinical animal models of inflammatory and neuropathic pain often produce weak evidence of impaired function. We hypothesized that hindpaw mechanical stimulation produced by a requirement to rear on a textured “NOX” plate would punish operant responding in rats treated with intraplantar complete Freund’s adjuvant (CFA, a model of inflammatory pain) or the chemotherapeutic paclitaxel (PTX, a model of neuropathic pain) and produce sustained pain-related depression of operant behavior. Male Sprague–Dawley rats were trained under a progressive-ratio (PR) schedule of food-maintained operant responding, then treated with CFA (100 µL in left hindpaw), PTX (2.0 mg/kg IP on alternate days for four total injections; 6.6 mg/kg IV on alternate days for three total injections), or saline vehicle. PR break points and mechanical thresholds for paw withdrawal from von Frey filaments were then tracked for 28 days. Subsequently, rats were tested with the opioid receptor antagonist naltrexone to assess latent sensitization and with the kappa opioid receptor (KOR) agonist U69593 to assess KOR function. CFA produced significant mechanical hypersensitivity for 3 weeks but decreased PR breakpoints for only 1 day. Both IP and IV PTX produced mechanical hypersensitivity for at least three weeks; however, only IV PTX decreased PR breakpoints, and this decrease was not alleviated by morphine. After recovery, naltrexone reinstated mechanical hypersensitivity in CFA- but not PTX-treated rats, and it did not reinstate depression of breakpoints in any group. U69593 dose-dependently decreased PR breakpoints in all groups with no difference between control vs. CFA/PTX groups. These results suggest that rearing on a textured NOX plate was not sufficient to punish operant responding in CFA- and PTX-treated rats despite the presence of sustained mechanical hypersensitivity. The rapid recovery of operant responding could not be attributed to latent sensitization, KOR downregulation, or behavioral tolerance. These results extend the range of conditions under which putative chronic pain manipulations produce weak evidence for depression of operant responding as a sign of the “affective/motivational” component of pain in rats.
Leukocyte Integrin Antagonists as a Novel Option to Treat Dry Age-Related Macular Degeneration
Authors: Baiula Monica , Caligiana Alberto , Bedini Andrea , Zhao Junwei , Santino Federica , Cirillo Martina , Gentilucci Luca , Giacomini Daria , Spampinato Santi
Published: January 2021

Age-related macular degeneration (AMD) is a complex multifactorial degenerative disease that leads to irreversible blindness. AMD affects the macula, the central part of the retina responsible for sharp central vision. Retinal pigment epithelium (RPE) is the main cellular type affected in dry AMD. RPE cells form a monolayer between the choroid and the neuroretina and are in close functional relationship with photoreceptors; moreover, RPE cells are part of the blood retina barrier that is disrupted in ocular diseases such as AMD. During ocular inflammation lymphocytes and macrophages are recruited, contact RPE and produce pro-inflammatory cytokines, which play an important role in AMD pathogenesis. The interaction between RPE and immune cells is mediated by leukocyte integrins, heterodimeric transmembrane receptors, and adhesion molecules, including VCAM-1 and ICAM-1. Within this frame, this study aimed to characterize RPE-leukocytes interaction and to investigate any potentially beneficial effects induced by integrin antagonists (DS-70, MN27 and SR714), developed in previous studies. ARPE-19 cells were co-cultured for different incubation times with Jurkat cells and apoptosis and necrosis levels were analyzed by flow cytometry. Moreover, we measured the mRNA levels of the pro-inflammatory cytokine IL-1β and the expression of adhesion molecules VCAM-1 and ICAM-1. We found that RPE-lymphocyte interaction increased apoptosis and necrosis levels in RPE cells and the expression of IL-1β. This interaction was mediated by the binding of α4β1 and αLβ2 integrins to VCAM-1 and ICAM-1, respectively. The blockade of RPE-lymphocyte interaction with blocking antibodies highlighted the pivotal role played by integrins. Therefore, α4β1 and αLβ2 integrin antagonists were employed to disrupt RPE-lymphocyte crosstalk. Small molecule integrin antagonists proved to be effective in reducing RPE cell death and expression of IL-1β, demonstrating that integrin antagonists could protect RPE cells from detrimental effects induced by the interaction with immune cells recruited to the retina. Overall, the leukocyte integrin antagonists employed in the present study may represent a novel opportunity to develop new drugs to fight dry AMD.
Dual Inhibition of γ-Tubulin and Plk1 Induces Mitotic Cell Death
Authors: Ebisu Haruna , Shintani Kana , Chinen Takumi , Nagumo Yoko , Shioda Shuya , Hatanaka Taisei , Sakakura Akira , Hayakawa Ichiro , Kigoshi Hideo , Usui Takeo
Published: January 2021

α/β-Tubulin inhibitors that alter microtubule (MT) dynamics are commonly used in cancer therapy, however, these inhibitors also cause severe side effects such as peripheral neuropathy. γ-Tubulin is a possible target as antitumor drugs with low side effects, but the antitumor effect of γ-tubulin inhibitors has not been reported yet. In this study, we verified the antitumor activity of gatastatin, a γ-tubulin specific inhibitor. The cytotoxicity of gatastatin was relatively weak compared with that of the conventional MT inhibitors, paclitaxel and vinblastine. To improve the cytotoxicity, we screened the chemicals that improve the effects of gatastatin and found that BI 2536, a Plk1 inhibitor, greatly increases the cytotoxicity of gatastatin. Co-treatment with gatastatin and BI 2536 arrested cell cycle progression at mitosis with abnormal spindles. Moreover, mitotic cell death induced by the combined treatment was suppressed by the Mps1 inhibitor, reversine. These findings suggest that co-treatment with Plk1 and γ-tubulin inhibitors causes spindle assembly checkpoint-dependent mitotic cell death by impairing centrosome functions. These results raise the possibility of Plk1 and γ-tubulin inhibitor co-treatment as a novel cancer chemotherapy.
Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial
Authors: Mao Wei , Yang Nizhi , Zhang Lei , Li Chuang , Wu Yifan , Ouyang Wenwei , Xu Peng , Zou Chuan , Pei Chunpeng , Shi Wei , Zhan Jihong , Yang Hongtao , Chen Hongyu , Wang Xiaoqin , Tian Yun , Yuan Fang , Sun Wei , Xiong Guoliang , Chen Ming , Guan Jianguo , Tang Shuifu , Zhang Chunyan , Liu Yuning , Deng Yueyi , Lin Qizhan , Lu Fuhua , Hong Weihong , Yang Aicheng , Fang Jingai , Rao Jiazhen , Wang Lixin , Bao Kun , Lin Feng , Xu Yuan , Lu Zhaoyu , Su Guobin , Zhang La , Johnson David W , Zhao Daixin , Hou Haijing , Fu Lizhe , Guo Xinfeng , Yang Lihong , Qin Xindong , Wen Zehuai , Liu Xusheng
Published: January 2021

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: −2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: −4.03,−0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects.

Clinical Trial Registration:http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.
Anti-Cholinergic Drug Burden Among Ambulatory Elderly Patients in a Nigerian Tertiary Healthcare Facility
Authors: Fadare Joseph O. , Obimakinde Abimbola Margaret , Aina Felix O. , Araromi Ebisola J. , Adegbuyi Theophilus Adekunle , Osasona Oluwatoba E. , Agbesanwa Tosin A.
Published: January 2021

Background: The use of drugs with anticholinergic effects among elderly patients is associated with adverse clinical outcomes. There is paucity of information about anticholinergic drug burden among Nigerian elderly population.

Objectives: To determine the anticholinergic drug burden among elderly Nigerian patients.

Methods: This was a retrospective cross-sectional study conducted among elderly patients (aged 65 and above) who visited the Family Medicine outpatients’ clinics of the Ekiti State University Teaching Hospital, Ado-Ekiti, Nigeria between July 1 and October 31, 2018. Information extracted from the case files included patient’s age, sex, diagnoses, and list of prescribed medications. Medicines with anticholinergic effects were identified and scored using the anticholinergic drug burden calculator (http://www.acbcalc.com).

Results: The medical records of 400 patients were analyzed with females accounting for 60.5% of the study population. The mean age of participants was 73 ± 7.4 years with only 28 (7%) of patients having more than two co-morbid conditions. Polypharmacy was identified in 152 (38%) of the patients while 147 (36.7%) had drugs with anticholinergic effects prescribed. The anticholinergic burden was high in 60 (15%) patients. Polypharmacy was significantly associated with having more than two diagnosed conditions and high anticholinergic burden (p value of < 0 .001 and 0.013 respectively). There was significant correlation between total number of prescribed drugs and count of diagnoses (r = 0.598; p < 0 .000) and between total number of prescribed drugs and number of drugs with anticholinergic effects (r = 0 .196; p < 0 .000).

Conclusion: The anticholinergic burden in this group of elderly Nigerian patients was low; majority (67%) had no exposure to drugs with anticholinergic effects with only 15% having high anticholinergic burden. Polypharmacy and multiple diagnosed conditions were positively associated with high anticholinergic burden. Based on the positive and significant correlations found in this study, a reduction in the number of prescribed medicines especially those with significant anticholinergic effects used for secondary indications may lessen the anticholinergic burden among the elderly.
The Kinase Specificity of Protein Kinase Inhibitor Peptide
Authors: Chen Yao , Sabatini Bernardo L.
Published: January 2021

G-protein-coupled-receptor (GPCR) signaling is exquisitely controlled to achieve spatial and temporal specificity. The endogenous protein kinase inhibitor peptide (PKI) confines the spatial and temporal spread of the activity of protein kinase A (PKA), which integrates inputs from three major types of GPCRs. Despite its wide usage as a pharmaceutical inhibitor of PKA, it was unclear whether PKI only inhibits PKA activity. Here, the effects of PKI on 55 mouse kinases were tested in in vitro assays. We found that in addition to inhibiting PKA activity, both PKI (6–22) amide and full-length PKIα facilitated the activation of multiple isoforms of protein kinase C (PKC), albeit at much higher concentrations than necessary to inhibit PKA. Thus, our results call for appropriate interpretation of experimental results using PKI as a pharmaceutical agent. Furthermore, our study lays the foundation to explore the potential functions of PKI in regulating PKC activity and in coordinating PKC and PKA activities.
Experience of Medical Disputes, Medical Disturbances, Verbal and Physical Violence, and Burnout Among Physicians in China
Authors: Wu Yinuo , Jiang Feng , Ma Jing , Tang Yi-Lang , Wang Mingxiao , Liu Yuanli
Published: January 2021

Background

Medical disputes, medical disturbances, verbal and physical violence against physicians, and burnout have reached epidemic levels. They may negatively impact both physicians and the healthcare system. The experience of medical disputes, medical disturbances, verbal, and physical violence, and burnout and the correlates in physicians working in public hospitals in China needed to be investigated.

Methods

A nationwide cross-sectional survey study was conducted between 18 and 31 March 2019. An anonymous online questionnaire was administered. The questionnaire included the 22-item Maslach Burnout Inventory-Human Services Survey (Chinese version). We also collected data on demographic and job-related factors, as well as physicians’ experiences of medical disputes, medical disturbances, verbal and physical violence from patients and the patients’ family members.

Findings

In total, 22,213 physicians from 144 tertiary public hospitals in all of China’s 31 provinces completed the survey. The overall burnout rate among the surveyed physicians was 31.28%. Moreover, 33.48% of physicians experienced disputes, 20.86% experienced disturbances, 48.52% experienced verbal violence, and 5.84% experienced physical violence in the past 12 months. Factors found to be significantly associated with burnout included younger age, being divorced or widowed, having a lower educational background, working in internal medicine departments, longer working hours per day, working in general hospitals, being in East China, as well as having experienced disputes, disturbances, and physical and verbal violence.

Interpretation

Close to a third of the Chinese doctors working in the tertiary hospitals reportedly experienced burnout, and the problem is related to the unsafe working environment caused by the worsening doctor-patient relationship.
Home Literacy Environment and Children’s English Language and Literacy Skills in Hong Kong
Authors: Lau Carrie , Richards Ben
Published: January 2021

Emerging evidence has shown a positive association between the home literacy environment (HLE) and monolingual children’s language and literacy development. Yet, far fewer studies have examined the impact of the HLE on second language development. This study examined relations between the HLE and children’s development of English as a second language in Hong Kong. Participants were 149 ethnic Chinese children (80 girls; Mage = 59 months, SDage = 10 months) and one of their caregivers. Caregivers completed questionnaires about their family backgrounds and HLE and children were assessed on their English language and literacy skills. Findings revealed considerable variability in the types of literacy activities that caregivers were engaged in at home with their children. A series of multilevel regressions demonstrated that the HLE was differentially associated with English vocabulary, letter knowledge, phonological awareness, and word reading skills after controlling for child and family characteristics. Results highlight the importance of a literacy-rich home environment for children’s development of English as a second language and the need to support caregivers in providing a range of home literacy activities to facilitate different language and literacy skills.
Online Self-Presentation Strategies and Fulfillment of Psychological Needs of Chinese Sojourners in the United States
Authors: Yang Tian , Ying Qianwei
Published: January 2021

This study statistically analyzed survey data to examine the relationship between fulfillment of psychological needs of 223 Chinese sojourners in the United States and their online self-presentation strategies on Chinese and American social media. The results showed that the combined use of proactive and defensive self-presentation strategies on Chinese social media instead of American social media were more effective to fulfill the sojourners’ need for autonomy. Moreover, presentation strategies that helped to meet the sojourners’ need for relatedness were significantly different between Chinese and American social media. Specifically, a proactive strategy was more effective to meet sojourners’ need for relatedness on Chinese social media, while a defensive strategy was more effective to fulfill their need for relatedness on American social media.
Study Protocol of a Distance Learning Intervention to Support Social Emotional Learning and Identity Development for Adolescents Using Interactive Mobile Technology
Authors: Cherewick Megan , Lebu Sarah , Su Christine , Richards Lisa , Njau Prosper F. , Dahl Ronald E.
Published: January 2021

Background: The maturational period from age 10 to 14—often referred to as very young adolescents (VYAs)—represents a dynamic period of learning and neurobehavioral development as individuals transition from childhood to adolescence. This developmental period presents a window of opportunity for strategic investment to improve trajectories of health, education and well-being among young people. More specifically, neurodevelopmental changes during pubertal maturation influence neural circuitry involved in processing emotions, risks, rewards and social relationships. Technology can be leveraged to create social emotional learning experiences for VYAs and provide opportunities for flexible, distance learning in low-income countries. The aim of this study protocol is to detail how insights from developmental science can be used to inform the intervention design, implementation and evaluation of a distance learning, social emotional learning intervention for VYAs.

Methods: This study will be delivered to 500 VYAs in Temeke District, Dar es salaam. Study participants will watch culturally-relevant, animated videos on social emotional mindsets and skills and content will be paired with experiential learning activities over a period of 10 weeks. A nested smart-phone based study will practice learning social emotional skills and mindsets through engagement with multi-media material via the WhatsApp messenger application. Surveys and in-depth interviews will be administered to adolescents, their parents/caregivers and teachers before and after the intervention to evaluate the effect of the intervention on study outcomes.

Discussion: This study is among the first to provide results on how to effectively design a distance-learning intervention to promote social emotional learning and identity development within a low-resource context. The findings will provide substantial evidence to inform new intervention approaches that are effective in low-resource contexts and strategies to reach scale among similar programs invested in leveraging technology to support adolescent health and development.

Clinical Trial registration: Study registered with ClinicalTrials.gov. Identifier number NCT0445807.
Model-Based Control and External Load Estimation of an Extensible Soft Robotic Arm
Authors: Chen Xiaojiao , Duanmu Dehao , Wang Zheng
Published: January 2021

Soft robotics has widely been known for its compliant characteristics when dealing with contraction or manipulation. These soft behavior patterns provide safe and adaptive interactions, greatly relieving the complexity of active control policies. However, another promising aspect of soft robotics, which is to achieve useful information from compliant behavior, is not widely studied. This characteristic could help to reduce the dependence of sensors, gain a better knowledge of the environment, and enrich high-level control strategies. In this paper, we have developed a state-change model of a soft robotic arm, and we demonstrate how compliant behavior could be used to estimate external load based on this model. Moreover, we propose an improved version of the estimation procedure, further reducing the estimation error by compensating the influcence of pressure deadzone. Experiments of both methods are compared, displaying the potential effectiveness of applying these methods.
Causes and Flock Level Risk Factors of Sheep and Goat Abortion in Three Agroecology Zones in Ethiopia
Authors: Alemayehu Gezahegn , Mamo Gezahegne , Alemu Biruk , Desta Hiwot , Tadesse Biniam , Benti Teferi , Bahiru Adane , Yimana Muhabaw , Wieland Barbara
Published: January 2021

A cross-sectional survey was conducted to estimate the incidence of small ruminant abortion and identify its major causes and potential risk factors in goat and sheep flocks in three agroecology and production systems of Ethiopia. Information on pregnancy outcomes and management risk factors were collected for 299 goat and 242 sheep flocks. Blood samples were collected from 133 sheep and 90 goat flocks and tested for Coxiella burnetii, Brucella spp., Chlamydia abortus, and Toxoplasma gondii. A causal diagram outlined relationships between potential predictor variables and abortion in the flock. The effect of management and exposure to infectious causes on the number of abortions in the flock across agroecology was tested using zero-inflated negative binomial regression. Results showed that 142 (58.68%) goats and 53 (17.73%) sheep flocks reported abortions in the 12 months before the survey. The mean annual flock abortion percentages were 16.1% (±26.23) for does and 12.6% (±23.5) for ewes. Farmers perceived infectious diseases, extreme weather conditions, feed shortage, physical traumas, and plant poisoning as the most important causes of abortion. A higher proportion of abortion was recorded during the short rainy season (March to May) and start of the short dry and cold season (June to August) in the lowland mixed crop-livestock and pastoral agroecology and production system, respectively. Overall, 65.41% sheep and 92.22% goat flocks tested positive for one or more abortion causing agents, namely, C. burnetti, C. abortus, Brucella spp., and T. gondii; mixed infection was found in 31.58% sheep and 63.33% goat flocks. Spending the night in a traditional house and providing supplementary feed for pregnant dams were important management factors which significantly (p ≤ 0.05) decreased the risk of abortion by 2.63 and 4.55 times, respectively. However, the presence of other livestock species and dogs in the household and exposure of the flock to Brucella spp. or anyone of the four tested infectious agents significantly (p ≤ 0.05) increased the risk of abortion in sheep and goat flocks. In general, abortion is a challenge for small ruminant production in the study area especially in lowland agroecology and calls for improvement in husbandry practices, health care and biosecurity practices.
The Burden of Drug Abuse in Nigeria: A Scoping Review of Epidemiological Studies and Drug Laws
Authors: Jatau Abubakar Ibrahim , Sha’aban Abubakar , Gulma Kabiru Abubakar , Shitu Zayyanu , Khalid Garba Mohammed , Isa Abubakar , Wada Abubakar S. , Mustapha Mohammed
Published: January 2021

Background: The burden of drug abuse is becoming a public health concern in Nigeria. Preventive measures should include identifying the root causes of the burden for targeted intervention. We, therefore, aim to conduct a scoping review of the literature to summarize the findings of epidemiological studies on drug abuse and provisions of drug laws in Nigeria. The review also provides appropriate recommendations as interventions for prevention.

Methods: We conducted a systematic search of the literature on PubMed to identify information on drug abuse and drug laws in Nigeria from the inception of the database to March 2020. Additional information was retrieved from Google Scholar, a manual search of included articles, discussion with experts on the subject matter, and gray literature. Study selection was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements. Information from gray literature was assessed for quality and accuracy using the AACODS checklist (authority, accuracy, coverage, objectively, date, significance).

Results: The systematic search of the literature generated 253 studies. Nine articles were obtained from other sources. After the selection process, 23 eligible studies were included for review. A prevalence of 20–40% and 20.9% of drug abuse was reported among students and youths, respectively. Commonly abused drugs include cannabis, cocaine, amphetamine, heroin, diazepam, codeine, cough syrup and tramadol. Sources where abusers obtained drugs, were pharmacies/patent medicine shops, open drug markets, drug hawkers, fellow drug abusers, friends, and drug pushers. Drug abuse was common among undergraduates and secondary school students, youths, commercial bus drivers, farmers, and sex workers. Reason for use included to increase physical performance, stress and to derive pleasure. Poor socioeconomic factors and low educational background were the common risk factors associated with drug abuse. We identified several drug laws and policies that were established under government agencies such as the National Drug Law Enforcement Agency (NDLEA), National Agency for Foods and Drugs Administration and Control (NAFDAC), Pharmacists Council of Nigeria (PCN) and a Presidential Advisory Committee.

Conclusion: Findings from epidemiological studies on drug abuse in Nigeria has demonstrated that the burden of drug abuse is still high despite the existing drug laws, policies, and strategies for prevention. Measures to reduce the burden should involve the community, government, and religious bodies. Preventive measures should target the youths, the students, identified sources of the drugs, reasons and risk factors associated with drug abuse in Nigeria.
An FPTAS for Dynamic Multiobjective Shortest Path Problems
Authors: Maristany de las Casas Pedro , Borndörfer Ralf , Kraus Luitgard , Sedeño-Noda Antonio
Published: January 2021

The Dynamic Multiobjective Shortest Path problem features multidimensional costs that can depend on several variables and not only on time; this setting is motivated by flight planning applications and the routing of electric vehicles. We give an exact algorithm for the FIFO case and derive from it an FPTAS for both, the static Multiobjective Shortest Path (MOSP) problems and, under mild assumptions, for the dynamic problem variant. The resulting FPTAS is computationally efficient and beats the known complexity bounds of other FPTAS for MOSP problems.
Phosphorus and Carbohydrate Metabolism in Green Bean Plants Subjected to Increasing Phosphorus Concentration in the Nutrient Solution
Authors: García-Caparrós Pedro , Lao María Teresa , Preciado-Rangel Pablo , Sanchez Esteban
Published: January 2021

Phosphorus (P) is considered an elementary mineral nutrient for plants. Nevertheless, excessive or deficit supply to the crop may cause negative changes at the physiological level. Plants were cultivated in pots in a growth chamber under increasing P concentration (P1 (0.5 mmol/L (control treatment)), P2 (1 mmol/L); P3 (2 mmol/L); P4 (4 mmol/L); P5 (6 mmol/L), and P6 (8 mmol/L)) in the nutrient solution for 40 days. At the end of the experimental period, biomass, carbohydrates concentration, and enzymatic activities related to the synthesis and degradation of sucrose as well as the different fractions of P in different organs of the plant were assessed. The results obtained in this experiment reveal a decrease in biomass under increasing P supply. Fructose, glucose, sucrose, and starch concentrations were higher in the shoots compared to the roots. There were different trends in the roots and shoots in enzymatic activities related to sucrose. The increase in P dose increased the concentration of the different forms assessed for P in all the organs studied. Seed phytate concentration surpassed the threshold established by the Food and Agriculture Organization (FAO) for green bean plants grown under P4, P5, and P6 treatments. Considering the results obtained, we suggest fertigation with a concentration of 2 mmol/L to obtain a higher productivity without excess of phytate in seeds.
Transcriptomic Changes Induced by Drought Stress in Hardneck Garlic during the Bolting/Bulbing Stage
Authors: Zhou Xiangjun , Condori-Apfata Jorge Alberto , Liu Xiaoqin , Condori-Pacsi Sandro Jhonatan , Valencia Maria Valderrama , Zhang Cankui
Published: January 2021

Garlic (Allium sativum L.) is an economically important, monocotyledonous plant with a strong taste and odor. Drought stress adversely affects its growth, development, and yield, particularly during the bolting/bulbing stage. Herein we performed RNA-seq to assess transcriptomic changes induced by drought stress in bolting/bulbing hardneck garlic plants (Purple Glazer). We observed that drought stress significantly reduced photosynthesis rate, fresh weight, and leaf water content. Transcriptomic analysis of garlic leaves under normal conditions and drought stress led to the identification of 5215 differentially expressed genes (2748 up- and 2467 downregulated). The upregulated DEGs were primarily involved in “biological process”, “metabolic process”, “oxidation-reduction process”, carbohydrate and lipid metabolism, and “proteolysis”, whereas the downregulated DEGs were mainly involved in “biological process” and metabolism of various molecules. In addition, genes encoding abscisic acid biosynthetic and catabolic enzymes, heat shock proteins, and E3 ubiquitin ligases were significantly altered by drought stress, indicating involvement in drought tolerance. A further comparison with the DEGs related to salinity stress-treated garlic revealed 867 and 305 DEGs with a similar and reverse expression alteration tendency, respectively.
Simulation of Granular Organic Fertilizer Application by Centrifugal Spreader
Authors: Zinkevičienė Raimonda , Jotautienė Eglė , Juostas Antanas , Comparetti Antonio , Vaiciukevičius Edvardas
Published: January 2021

There is no specialized equipment designed to spread granular cylindrical organic fertilizer in the soil. There are also no rational recommendations available on how to spread this type of fertilizer. Mineral fertilizer spreaders are most often used for spreading granulated organic fertilizer. However, these fertilizers are significantly different from mineral fertilizers. Due to these differences, organic granular fertilizers often are spread unevenly, and the fertilizer does not reach the required working width. Furthermore, the rate of spreading is not accurate, and the fertilizer is often crushed too much. The objective of this research is to develop a simulation model for granular organic fertilizer applications with a centrifugal spreader in EDEM (extended distinct element method) software. It is possible to develop a numerical model that corresponds to a real spreader, and to determine the key physical–mechanical parameters for the application of granular organic fertilizer. This model can also be used for evaluating the transverse uniformity of the fertilizer in the field (along the trajectory normal to the machine). The results of this research show that the distance traveled by the fertilizer granules partially depends on the particle size, initial speed, type of fertilizer and the parameters of the spinning discs of the spreader.