bluuebunny/crossref_metadata_2025 huggingface dataset:
Representative Farming and Non-Farming Communities as a Dynamic Mirror of Unidimensional Poverty in Pakistan
Authors: Qadir Aneela , Arshad Muhammad , LI Guangming , Rafique Muhammad
Published: September 2022

This research examines rural and urban poverty in Pakistan on a national and provincial scale, examining its many facets. Using the HIES/PSLM data of Pakistan, which is recognized internationally, from 2013–14 to 2018–19, and two well-respected indexing approaches (FGTI for single-dimensional poverty and Alkire & Foster for multidimensional poverty), we can examine the evolution of poverty in Pakistan over the past five years. According to the findings of the time series analysis, poverty shows a mixed (rising and falling) pattern over a shorter time frame (1–2 years) and a declining trend over a longer time frame (national and provincial levels, farming, and non-farming communities) overall (at least 05 years). In Pakistan, empirical data shows that poverty has decreased by 45.1% (32.1%) among farming and non-farming communities over the past five years. The results reveal a downward trend across Pakistan's provinces, except for Baluchistan. Specific poverty declines by 46.29 percent (36.15 percent) in Punjab, 71.1 percent (75.0 percent) in KPK, and 37.0 eight percent (2.0 percent) in Sindh. Baluchistan's farming (non-farming) communities have been getting poorer, from 20.64 percent to 61.28 percent. Punjab and Sindh provinces are Sutor’s contributors to overall poverty, as seen by the decomposition of the population by the group for uni-dimensional poverty. Reduce poverty in both regions using a single-pronged approach by boosting economic growth and expanding employment options.
Development and validation of a type 2 diabetes machine learning classification model for clinical decision support framework
Authors: Glanz Victor , Dudenkov Vladimir , Velikorodny Alexey
Published: September 2022

Undiagnosed type 2 diabetes is very common and represents a significant challenge for all national healthcare systems. Although diagnostic criteria and laboratory screening procedures are well-established, clinical tests have limitations, and in many cases diagnosis confirmation and more precise interpretation of the tests results are required. Machine learning methods, when applied to clinical outcomes risk prediction, demonstrate great effectiveness as they recognize specific patterns in data dynamics and thus can be used for identification of at-risk cases where diabetes and complications can be delayed or even prevented. We developed and validated a machine learning classification model for type 2 diabetes that possesses several important advantages over conventional methods (FINDRISC, ADA risk score), including mean values of 0.959, 0.92 and 0.89 for AUC, specificity and sensitivity, respectively. The study results potentially have major clinical implication, as the model is able to exchange data with electronic health records. Thus, it can be employed in clinical decision support framework together with other diabetes, cardiovascular disease models and models for related conditions.
Impact of two irrigation scheduling techniques on water use efficiency and yield of potato crop (Solanum tuberosum L.) grown in sandy soils
Authors: Fatouh I. I. , Helmy A. M. , Fouda S. E. , Khalil M. M. , Shaddad S. M.
Published: September 2022

Due to water scarcity in arid and semi-arid region there is a need to save each drop of water especially water used for irrigation. This can be achieve using the irrigation scheduling technique that allow to precisely calculate the crop water requirements and adding them when needed. The experiment was carried out to compare the ETc values (FAO method) and Crop-R method basically based on climatic data with the exception that Crop-R uses soil moisture probe for providing real data information. The two methods were applied under field condition irrigated by center pivot system of Potatoes crop (Solanum tuberosumsp.) grown on a new reclaimed soils in Wadi El-Natroun, Egypt. To study the water use efficiency (WUE) and yield productivity of potato during growing seasons 2019/2020 Comparing the two irrigation methods results showed that Crop-R method surpassed ETc values method in terms of water use efficiency (WUE), maximum plant height, yield and number of irrigation events. Values of WUE, maximum plant height, yield and numbers of irrigation events for ETc were 8.31 kg m-3, 60 cm, 31.60 Mg ha-1 and 56, respectively. Whereas, for Crop-R the values were 10.30 kg m-3, 60 cm, 32.66 Mg ha-1 and 53, respectively. The results of this study encourage the use of Crop-R method since it allows save water, maximizing the yield and reducing energy due to minimizing the number of irrigation events, to achieve profitability and ultimately sustainability.
Increased working memory load does not modulate the attentional blink
Authors: Skiba Helena , Keil Julian
Published: September 2022

The human capacity to process and encode stimuli in working memory is limited, and one way to test this capacity is the attentional blink. In this paradigm, participants are usually able to correctly identify a first target but fail to correctly identify a second target presented shortly after. In the current experiment, we combined the attentional blink paradigm with a visual working memory manipulation to examine the modulation of the target identification by reduced cognitive capacity. Bottleneck theories predict an increased attentional blink with limited resources. In contrast, the overinvestment hypothesis predicts an inverted-u shaped relationship between attentional resources and the attentional blink. In support of the former explanation, we found an increase in the attentional blink with increasing working memory load. However, we did not find an interaction between the target lag and the working memory load, which indicates that the working memory load did not modulate the attentional blink but affected the perceptual encoding of the second target.
In times of need. Cross-country investigating of the determinants of aid allocation for Ukraine during the 2022 Russian invasion
Authors: Trepanowski Radosław , Drążkowski Dariusz , Burdun Patryk , Bojarski Dawid
Published: September 2022

In August 2022, the Russian Federation’s invasion on Ukraine had already been happening for almost six months. During this time, many world governments aided Ukraine. In this paper, we examine geographical, economic, sociocultural, political, and defensive determinants of bilateral aid allocated to Ukraine on cross-national data from 87 countries. Our model explains 59% of total bilateral aid variance and shows that NATO and EU affiliation and high exports to Ukraine were related to higher aid volume. Our analysis contributes to a better understanding of aid allocation to Ukraine during the Russian invasion and suggests that countries might provide aid to enhance military safety of the Euro-Atlantic area, implement EU policies, and protect their own economic interests in Ukraine. Thus, the aid provided to Ukraine seems to serve donors’ foreign policy strategy drived at security, political, and trade interests.
Warning of a forthcoming collapse of the Atlantic meridional overturning circulation
Authors: Ditlevsen Peter , Ditlevsen Susanne
Published: September 2022

Tipping to an undesired state in the climate, viewed as a complex system, when a control parameter slowly approaches a critical value (λ(t) → λc) is a growing concern with increasing greenhouse gas concentrations. Predictions can rely on detecting early warning signals (EWS) in observations of the system. The primary EWS are increase in variance, due to loss of resilience, and increased autocorrelation or critical slow down. These measures are statistical in nature, which implies that the reliability and statistical significance of the detection depends on the sample size in observations and the magnitude of the change away from the base value prior to the approach to the tipping point. Thus, the possibility of providing useful early warning depends on the relative magnitude of several interdependent time scales in the system. These are (a) the time before the critical value λc is reached, (b) the (inverse) rate of approach to the bifurcation point, (c) the size of the time window required to detect a significant change in the EWS and finally, (d) the escape time for noise-induced transition (prior to the bifurcation). Conditions for early warning of tipping of the AMOC are marginally fulfilled for the existing past ~150 years of proxy observations where indicators of tipping have recently been reported. Here we provide statistical significance and estimate a collapse of the AMOC to occur around year 2050.
Evaluation of food homogenates on cell survival: pilot study for the in vitro analysis of infectious foodborne HEV
Authors: Semaan Dima , O'Connor Liam , Scobie Linda
Published: September 2022

A critical review on the approaches to assess the infectivity of the Hepatitis E virus (HEV) in food recommended that a cell culture-based method should be developed. Due to the observations that viral loads in food may be low, it is important to maximise the potential for detection of HEV in a food source in order to fully assess infectivity. To do so, would require minimal processing of any target material. In order to proceed with the development of an infectivity culture method that is simple, robust and reproducible, there are a number of points to address; one being to assess if food homogenates are cytotoxic to HEV susceptible target cells. Food matrices previously shown to have detectable HEV nucleic acid were selected for analysis and assessed for their effect on the percentage survival of three cell lines commonly used for infectivity assays. Target cells used were A549, PLC/PRF/5 and HepG2 cells. The results showed that, as expected, various food homogenates have differing effects on cells in vitro. In this study, the most robust cell line over a time period was the A549 cell line in comparison to HepG2, with PLC/PRF/5 cells being the most sensitive. Overall, this data would suggest that FH can be left in contact with A549 cells for a period of up to 72 hours to maximise the potential for testing infection. Using food homogenates directly would negate any concerns over losing virus as a result of any additional processing steps.
The effectiveness of Flubendazole in Capillaria spp. infections in female European hedgehogs (Erinaceus europaeus) in a hedgehog rescue centre in the Netherlands
Authors: Sandt C.M.G. van der , Elderen M. van
Published: September 2022

The European hedgehog is host to many parasites. Common endoparasites are Capillaria spp. (Lung threadworm, Intestinal threadworm spp.). Eggs and worm larvae are present in the faeces of infected hedgehogs. Common applied anthelmintic drugs are Fenbendazole and Levamisole. The latter might cause abortions in female hedgehogs. For this reason, some hedgehog centres in the Netherlands prefer Flubenol (Flubendazole 5%) in female hedgehogs. The present study aimed to determine the effect of Flubenol in Capillaria spp. infections in female hedgehogs. The faeces of 10 infected female hedgehogs before and after treatment with Flubenol has been examined. In the faeces samples of 7 out of 8 hedgehogs after treatment, no Capillaria eggs were found. One worm egg was found in the faeces sample of one hedgehog. No worm larvae were found in the faeces samples of 6 out of 7 hedgehogs after Flubenol treatment. Eight worm larvae were found in the faeces sample of one hedgehog after treatment. The Wilcoxon Signed-Rank Test indicated for both the Capillaria spp. eggs and the larvae a significant difference at p < 0.05 before and after the Flubenol treatment.
Hybrid deep neural network models for boosting Human Activity Recognition using IoT wearables
Authors: S SOWMIYA , D MENAKA
Published: September 2022

Human Activity Recognition is a key element for many immense applications in human life. With the advances in sensor technologies and utilizing the IoT, HAR has a wide area of research with the help of deep learning algorithms. The advanced deep learning paradigm provides end-to-end learning models from unstructured, complex data. IoT wearables and smartphones are now widely used embedded with mobile apps for telemedicine, e-health monitoring, sports monitoring, AAL, biometrics, smart homes etc. This paper presents hybrid neural networks model implemented with Bidirectional GRU, Bidirectional LSTM and CNN. The algorithm was tested using three activity recognition datasets WISDM ,USCHAD and MHEALTH. The hybrid model provides improved accuracy over the other activity recognition techniques.
The Influences of Social Distance on Anxiety Caused by Spatial and Temporal Distance
Authors: Gao Yuan , Zhang Qun , He Rui , Liao Jiejie , Feng Huiyan , Deng Hongyu , Hu Yuan , Mo Lei
Published: September 2022

Psychological distance is explored extensively in the field of social cognition. Recently, some researchers have advanced the researches of psychological distance to the emotional domain, exploring the effects of single dimension of psychological distance on anxiety triggered by negative events. On the basis, the present study further explored the interaction effect of different social distance on the temporal and spatial distance effect of anxiety triggered by negative events. Experiment 1 explores the effect of zero social distance on the temporal (Experiment 1a) and spatial (Experiment 1b) distance effect of anxiety induced by negative events. Experiment 2 explores the effect of near social distance on the temporal (Experiment 2a) and spatial (Experiment 2b) distance effect of anxiety induced by negative events. The results of Experiment 1 showed that the temporal and spatial distance of the event make individual more anxious when the negative event occurs to the individual himself rather than others. The results of experiment 2 showed that the temporal and spatial distance of the event make individual more anxious when the negative event occurs to the individual’s friends rather than others. Based on the results of two experiments, this study proposed the influence pattern and significance of social distance on the spatial and temporal distance effect of anxiety caused by negative events.
Antibiotic combination therapy versus monotherapy for the treatment of infections due to carbapenem-resistant Gram-negative bacteria： a systematic review and meta-analysis
Authors: Lai Chengcheng , Ma Zijun , Zhang Jun , Wang Junjun , Wang Jinghui , Wu Zhuanghao , Luo Yonggang
Published: September 2022

Background: Increasing evidence has suggested that combination antibiotic therapy is more effective than monotherapy and leads to better outcomes.However, results from observational researches were contradictory and did not support the combination antibiotic therapy in this context. Here, a meta-analysis of published studies determined whether a combination of two or more antimicrobial agents reduces mortality in patients with Gram-negative bacteremia.
Objective: The aim of the review was to comprehensively summarize the evidence and evaluate the impact of antibiotic combinations or monotherapy on infection caused by carbapenem-resistant Gram-negative bacteria.
Method: A comprehensive computerized search was performed through PubMed, Cochrane library, web of science and Embase up to March 15, 2012, to identify published studies. We would include randomized controlled trials, non-randomised studies without consideration of publication status, time of publication, blinding status or language. Case reports, review articles were excluded. Studies were considered available if they compared monotherapy regimens with combination therapy regimens for treating infection due to carbapenem-resistant Gram-negative bacteria.
Results: A total of 52 studies were included enrolling 6524 participants, which included 5 randomized controlled trials and 47 non-randomised studies of the effects of interventions. The results showed higher mortality (OR=1.38, 95%CI=1.17-1.64) in monotherapy groups, lower clinical success (OR=0.63, 95%CI=0.45-0.89) and microbiological eradication (OR=0.60, 95%CI=0.43-0.84) in monotherapy for treating carbapenem-resistant Gram-negative bacteremia. Similarly, significant higher mortality (OR=1.58, 95%CI=1.22-2.06), lower clinical success (OR=0.36, 95%CI=0.24-0.53) and microbiological eradication (OR=0.36, 95%CI=0.18-0.72) in monotherapy for treating carbapenem-resistant Enterobacteriaceae. There were only few clinical researches comparing the effect of combination therapy versus monotherapy, most of them being case-control and retrospective cohort studies limited by small study size. Well- argued randomised controlled trials are lacking.
Conclusions: Infection patients caused by carbapenem-resistant Gram-negative bacteria may benefit from combination therapy. We suggest choosing combination therapy to treat severe infection due to carbapenem-resistant Gram-negative bacteria before larger and better-devised randomized controlled trials completed. Because of risk and the design of the available studies, well-powered randomized controlled trials are needed.
Aspergillus lentulus Activates the NLRP3 Inflammasome
Authors: Yusufujiang Xiarikeya , Wang Xiaodong , Zhang Lijuan , Abulizi Palida
Published: September 2022

Aspergillus lentulus (A.lentulus) as a sibling species of Aspergillus fumigatus can cause fatal invasive aspergillosis in immunocompromised patients. Innate immunity is the first line of anti-infection reactions. The NLRP3 inflammasome is an essential protein complex of innate immunity that controls the secretion of IL-1β. Previous studies have shown that NLRP3 inflammasome plays an important role in fungal infection. In present study, to clarify whether A.lentulus is able to activate the NLRP3 inflammasome, mouse dendritic cells (DCs) used as infection model and analyzed IL-1β production after incubating with A.lentulus strain isolated from a COPD patient. The result showed that A.lentulus-induced IL-β secretion is depend on NLRP3 inflammasome activation, it was determined by gene-specific siRNA. Further more, the effect of K+ efflux, Cathepsin B or ROS production to the IL-1β secretion were confirmed by competitive inhibitors. Our data indicates that A.lentulus activates NLRP3 inflammasome and induce IL-1β production from DCs.
CT findings of chemotherapy drug-related acute pancreatitis
Authors: Zuo Liping , Fan Jinlei , Shi Shuo , Tian Ziyu , Yu Dexin
Published: September 2022

Purpose
To describe plain and contrast-enhanced computed tomography (CT) findings of chemotherapy drug-related acute pancreatitis in patients with malignances.
Methods
Twenty-two patients with first clinical and/or biochemical evidence of pancreatitis who underwent plain and/or contrast-enhanced CT while being treated with chemotherapy were retrospectively included in the study. Chemotherapy drug-related acute pancreatitis (CDRAP) diagnosis was obtained based on clinical, imaging, and biochemical findings. CT features of CDRAPwere recorded as follows: normal pancreas morphology, pancreatic enlargement (diffuse or focal), enhancing but heterogeneous parenchyma (diffuse or focal), peripancreatic stranding, acute peripancreatic fluid collection, pseudocyst, acute necrotic collections (pancreatic necrosis and peripancreatic necrosis) and main pancreatic duct dilatation. In addition, the baseline demographics, clinical, biochemical, other complications, chemotherapy drugs, and outcomes of the pancreas were also included.
Results
CT showed that five (23%) patients demonstrated normal pancreas, whereas 17 (77%) patients presented with acute pancreatitis changes in clinically diagnosed CDRAP patients. The CT findingsof 22 CDRAPs were as follows: diffuse (n=7) or focal (n=8) pancreatic enlargement, diffuse (n=6) or focal (n=1) heterogeneousenhancement, peripancreatic stranding (n=5), acute peripancreatic fluid collection (n=7), and pseudocyst (n=1). No patients developed acute necrotic collections or dilatation of the main pancreatic duct. The severity classification of acute pancreatitis in most people (81%) wasmild pancreatitis. Other complications were drug-induced hepatitis (n=3), polycranial neuropathy (n=1), and death (n=1).Regarding theoutcomes of the pancreas, two patients developed acute pancreatitis changes on CT in five initial normal pancreas morphologies.
Conclusion
Chemotherapy-related acute pancreatitis mainly presented as interstitial edematous pancreatitis and/or a normal pancreas on CT. Most living patients experienced mild acute pancreatitis. Patients with other risk factors for acute pancreatitis might easily develop CDRAP, which needs more attention.
Experimental Investigation of Hybrid PCM Polyethylene glycol with Al 2 O 3 and CuO nanoparticles
Authors: Ansu A.K. , Pandya Mohit , Sharma R. K. , Tripathi D.
Published: September 2022

The authors have requested that this preprint be removed from Research Square.
Variations in the type of adjuvant chemotherapy among Stage III colon cancer patients in England
Authors: Hassan Syreen , Miles Anne , Rachet Bernard , Morris Melanie
Published: September 2022

Purpose: Treatment with any adjuvant chemotherapy for Stage III colon cancer has been shown to differ between groups. Few studies, however, explore variations in the type of adjuvant chemotherapy received, none of which from the UK. The aim of this study is to explore variation in the type of chemotherapy received by Stage III colon cancer patients.
Methods: Data from the national cancer registry was linked to the Systemic Anti-Cancer Therapy database, which provides detailed information on treatment of malignant diseases from all NHS England chemotherapy providers. Demographic and clinical characteristics were compared between those who received monotherapy (fluoropyrimidine) or combination chemotherapy (fluoropyrimidine and oxaliplatin) among Stage III colon cancer patients.
Results: Of 8,750 patients who received adjuvant chemotherapy, 22.3% (n=2,359) received monotherapy and 60.4% (n=6,391) received combination therapy. The odds of receiving combination therapy decreased with age. Those from the most deprived group had half the odds (OR: 0.5, CI: 0.42,0.59, p<0.001) of receiving combination therapy compared to the least deprived group. Women were 14% less likely to get combined therapy (OR: 0.86, CI: 0.77,0.95, p=0.005). Those with the largest tumour size (T4) and those with more than 3 lymph nodes involved (N2) had 30% (OR: 1.30; CI: 1.07,1.59; p=0.008) and 50% (OR: 1.50; 1.34,1.69; p<0.001) higher odds of receiving combination therapy compared to T1 or T2 and N1, respectively.
Conclusion: There is variation in the type of chemotherapy received for stage III colon cancer patients by sociodemographic factors, despite clear clinical guidelines.
The efficacy, safety and pharmacokinetics of IL-17A monoclonal antibody injection (AK111) in patients with moderate to severe plaque psoriasis: a randomized, double-blind, placebo-controlled phase Ib multi-dose escalation clinical study
Authors: Jiang Congjun , Zhou Huan , Zhang Wanlu , Xia Yu , Li Baiyong , Ni Xiang , Wang Guoqin , Zhang Wenhui , Chen Benchao , He Zhimei , Zhang Min , Chen Rui , Jin Hongzhong , Deng Liehua
Published: September 2022

Objectives
To evaluate the safety, tolerability, immunogenicity, pharmacokinetics (PK), pharmacodynamics (PD), and the expression of skin biomarkers of AK111 injection after multiple administration in subjects with moderate to severe plaque psoriasis, and to evaluate the preliminary clinical efficacy in the trial.
Methods
This study is a randomized, double-blind, placebo-parallel controlled study using a dose escalation mode of multiple doses. 48 subjects were sequentially randomized to receive each of AK111 dose regimens (75mg, 150mg, 300mg, 450mg) or corresponding placebo. All subjects were treated with the study drug at week 0/1/4/8 and were unblinded at week 12 with the placebo group being ended, and AK111 group being followed up to 20 weeks.
Results
A total of 48 subjects were randomized. At week 12, compared with placebo, the percentage of subjects achieving PASI75 and sPGA0/1 in AK111 75mg, 150mg, 300mg, and 450mg dose groups was significantly increased, and higher PASI90 was achieved in 150mg, 300mg, and 450mg dose groups than in 75mg group. All efficacy indicators were maintained at week 20. The incidence of treatment-emergent Anti-Drug Antibody (ADA) was 0%(0/48). Neutralizing antibodies (Nabs) were not detected in any subject. The proportion of subjects with any reported treatment-emergent adverse event (TEAE) was 75.0% in the AK111 group, similar to 66.7% in the placebo group, and there was no obvious dose relationship. The most commonly reported adverse events were hyperglycemia, elevated blood pressure and hypokalemia. Additionally, the AK111 PK showed approximate dose proportionalitywith regard to the PK parameters of the Cmax and AUC0-tfollowing subcutaneous injection doses of 150mg,300mg and 450 mg.
Conclusion
After moderate to severe plaque psoriasis subjects received multiple subcutaneous AK111 injections,the dose range of 150mg-450mg, AK111 exposure increased in an approximate dose-proportional relationship. AK111 was demonstrated to be safe and tolerable. In subjects with moderate to severe plaque psoriasis, AK111 demonstrated encouraging preliminary efficacy which was sustained in a relatively long period after the last dose administration.
Clinical trial registration
Clinical trial identification number is NCT05504317 and was registered in August 2022
Biotransformation of Ginsenoside Rb2 to Rg3 by Endophytic Bacterium Leifsonia sp.G05 isolated from Dry Panax ginseng
Authors: Guo Min , Xu Yanyan , Zhang Chen , Zhu Runqi , Liang Cancan , Liu Jialin , Zhu Daheng
Published: September 2022

In this study, a strain G05, which can efficiently convert the main ginsenoside Rb2 to the rare ginsenoside Rg3, was screened from the endophytic bacteria of dry Panax ginseng by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) analysis. The strain was identified as Leifsonia by morphological and molecular biological analysis and named Leifsonia sp.G05. The effect of medium, inoculum amount, transformation temperature, medium pH and substrate concentration on the conversion rate of ginsenoside Rb2 to Rg3 was investigated to obtained the optimum conditions for transformation and high conversion rate, as well as the transformation path of strain G05. The results showed that the strain G05 could convert 1 mg/mL ginsenoside Rb2 more efficiently when the medium was Luria-Bertani, the inoculum amount was 1%, the transformation temperature was 30°C, and the medium pH was 7. Under these conditions, the main ginsenoside Rb2 could be nearly completely converted to the rare ginsenoside Rg3 by strain G05 after 9 hours of fermentation, the conversion rate reached 98%, and the transformation path was Rb2→Rd→Rg3. The research results could improve the utilization rate of the main ginsenoside Rb2 to a certain extent, and provide safer and specific rare ginsenosides for the pharmaceutical and food preparation industries.
Architecture, domain organization and functional signatures of trypanosomatid keIF4A1s and Plasmodium peIF4A1s suggest conserved functions
Authors: Dadwal Anica , Das Supratik
Published: September 2022

Initiation of translation is the first of the three obligatory steps required for protein synthesis and is carried out by a large number of protein factors called initiation factors in conjunction with ribosomes. One of the key conserved protein factors in eukaryotes that plays a role in this process is eIF4A which has three homologues in humans with eIF4A1 being the primary factor playing a role in translation initiation. eIF4As are members of a family called DEAD-box helicases that carry out different biological functions. eIF4A1s are recruited to translation initiation complexes via association with eIF4G and have ATP binding, ATP hydrolysis, RNA binding and unwinding activities. Plasmodium and trypanosomatids like Leishmania and Trypanosoma are parasites that cause human disease. While mechanistically the function of eIF4A1s in eukaryotes is well understood, the orthologues peIF4A1s and keIF4A1s in Plasmodium and trypanosomatids are not well studied. Here, we have used bioinformatics tools and homology modeling to study the motifs and functional signatures of Plasmodium and trypanosomatid peIF4A1s/ keIF4A1s. We report that inspite of the great divergence in evolution between these parasites and higher eukaryotes there is remarkable conservation of motifs and functional signatures in Plasmodium and trypanosomatid peIF4A1s/ keIF4A1s.
Therapeutic potential of FLT4-targeting peptide in acute myeloid leukemia
Authors: Lee Ji Yoon , Park Soojin , Han A-Reum , Hwang Hee-Sun , Kim Hee-Je
Published: September 2022

Background: Fms-related tyrosine kinase-4 (FLT4) is involved in tumor progression. Previously, we found that dysfunctional natural killer (NK) cells with low interferon-gamma (IFN-γ) were restored in acute myeloid leukemia (AML) by the FLT4 antagonist MAZ51. We developed 12 peptides targeting FLT4 for clinical application and ultimately selected 4 of them to examine whether they restored the frequency of lymphocytes, especially T cells and NK cells, and high IFN-γ expression, as MAZ51 treatment did in our previous study. Although clinical data from using intracellular kinase domain–targeting peptides are currently available, peptides targeting FLT4 to modulate immune cells have not been fully elucidated.
Methods: To end this, designed 12 peptides were screened in vitro their potential for IFN-gamma expression by ELISpot assays. And then 4 peptides were finally selected to apply leukemic mice. To assess the changes of immune subset in leukemic mice, FACS analysis was performed using BM, PB, and spleen from leukemic mice.
Results: In this study, we focus on novel peptide 4 (P4) from the intracellular domain of FLT4 because it had dominant negative activity. Similar to MAZ51, high IFN-γ levels were expressed in AML-mononuclear cells (MNCs) exposed to P4. In addition, T and NK cell levels were restored, as were high IFN-γ levels, in a leukemic environment when P4 was co-cultured with cytosine β-D-arabinofuranoside. Interestingly, the frequency of regulatory T cells was significantly decreased by P4, implying that the peptide plays a role in modulating the tumor niche.
Conclusion: Overall, we demonstrated the therapeutic value of functionally modulating lymphocytes using a peptide targeting FLT4 and propose the development of advanced therapeutic approaches against AML by using immune cells.
A high-throughput methodology for the efficient isolation of highly pure extracellular vesicles from skeletal muscle myoblasts
Authors: Fernández-Rhodes María , Adlou Bahman , Williams Soraya , Jalal Aveen R. , Lewis Mark P. , Davies Owen G.
Published: September 2022

Background: Skeletal muscle extracellular vesicles (SM-EVs) regulate gene expression events in myogenic differentiation. Optimising effective SM-EV isolation methods offering high levels of purity will be important to accurately define their composition and functionality. Size-exclusion chromatography (SEC) applied in combination with ultrafiltration (UF) has the potential to increase sample throughput, scalability and selectivity. However, an optimal UF+SEC methodology has not been tested for the isolation of myotube derived EVs. Our aim was to compare two different UF protocols and define an optimal window of SEC fractions to maximise SM-EVs recovery and sample purity.
Methods: C2C12 myotube conditioned medium was pre-concentrated using Amicon® Ultra 15 or Vivaspin®20, 100KDa UF columns and processed by SEC (IZON, qEV 70nm). The resulting thirty fractions obtained were individually analysed to identify an optimal fraction window for EV recovery.
Results: EV markers Alix and TSG101 could be detected up to fraction 13, while CD9 and Annexin A2 only up to fraction 6. ApoA1+ lipoprotein contaminants were detected from fraction 6 onwards for both protocols. Amicon and Vivaspin UF preconcentration protocols led to qualitative and quantitative variations in EV marker profiles and purity. Eliminating lipoprotein co-isolation by reducing the SEC fraction window resulted in a net loss of particles, but increased measures of sample purity and had only a negligible impact on the presence of EV marker proteins.
Conclusion: In conclusion, this study developed optimal UF+SEC protocols for the isolation of SM-EVs based on sample purity (fractions 1-5) and total abundance (fractions 2-10). The resulting protocols will be valuable in isolating highly pure SM-EV preparations for biomarker studies.
Optimization, Evaluation and Delivery of Genistein Loaded Long Circulating Nanostructured Lipid Carriers for Treatment of Cancer Melanoma Cells
Authors: Dewangan Hitesh Kumar , Maurya Lakshmi , Sharma Rajiv , Shah Kamal , Soni Surbhi , Singh Sanjay
Published: September 2022

Genistien is a soy isoflavone phytoestrogen, BCS class IV drug that has been efficacious for treatment of melanoma. Therefore, prepared Genistien loaded nanostructured lipid carriers (GEN-NLCs) for controlled and target delivery to melanoma cells. GEN-NLCs were formulated by solvent diffusion method applied Thogonal Taguchi optimization. Prepared GEN-NLCs were characterized by their physicochemical quality like particle size, zeta potential, morphology (SEM and AFM), entrapment efficiency, in-vitro release, and incompatibility studied such as DSC, and XRD. In-vitro anticancer and cellular uptake studies were accomplished in MTT assay method and A-375 melanoma cell-line by fluorescence-microscopy technique. Nanogel was prepared by incorporating optimized batch of GEN-NLC in methocel and evaluated for particle size and mechanical properties, In-vitro and ex- vivo occlusion studies, in-vitro release and ex-vivo human cadaver skin permeation and retention studies. Prepared GEN-NLCs were found to be a smooth surface with particle size 189.90±2.45 nm, 89.50±4.52% EE, -14.98±1.4mV zeta potential, and sustained release. MTT assay revealed that nanoparticles were 15.37 times more effective against melanoma as compared to pristine drugs. There was no significant change in texture profile of nanogel after incorporating GEN-NLC. Moreover, a significant increase in occlusivity was observed with occlusion factor almost 3.75 times more than control gel at end of 24 h. Ex-vivo studies further confirmed decrease in flux across skin i.e. sustained release pattern of GEN from hydrogel and increased hydration and retention in epidermis. Therefore, topical delivery of GEN-NLC loaded gel showed potential delivery system to target skin epidermis for melanoma cancer cells with enhanced efficacy.
Supplement of probiotics improves the meat output and quality of near maturity yellow-feathered broilers
Authors: Peng Hao , Yin Yangyan , Pei Zhe , Wei Tianchao , Li Jun , Li Xiaoning , Li Changting , Bai Huili , Ma Chunxia , Gong Yu , Liao Yuyin
Published: September 2022

To investigate effects of Lactobacillus plantarum and Bacillus subtilis as feed additives on the growth performance of near maturity yellow-feathered broilers. A total of 75 100-day-old hens were randomly divided into five groups. 1% of L.plantarum(P-group), B.subtilis (B-group), a 1:1 mixture of both strains(PB-group), or commercial probiotic production（M-group）were added into the drinking water at a concentration of 1.5x109 cfu/mL respectively. The control group was fed basal diet. Our results showed that L.plantarum could increase the intestinal enzyme activity of broilers, while decreasing the plasma MDA content, increasing the ALB and TP content, decreasing the plasma AST content, increasing the concentrations of plasma IgA and CD8 molecules, improving the jejunum structure. Meanwhile, B.subtilis increased the concentration of plasma AST and CD8 molecules of broilers. Additionally, B.subtilis also increases the plasma GSH-Px content, but not affecting the plasma biochemical indexes. And increases the plasma IgG and GSH-Px contents and the VCR ratio also improved in M-group. Additionally, the methionine content in thoracic muscle was increased in all groups. But only adding probiotics groups increase the relative abundance of broiler intestinal phylum Synechococcus and Phylum Firmicutes while decreasing the relative abundance of Enterococcus spp. Our results showed that adding probiotics could improve the meat output and quality. It might also be necessary to optimize the feeding conditions by selecting specific strains according to different effects of those probiotics, and to evaluate the best viable number of probiotics which survives in broiler guts to balance the cost and the effort.
Left ventricular pressure strain loops for evaluation on myocardial work in type 2 diabetic patients with or without hypertension
Authors: HUANG Mei-feng , YUAN Xin-chun , ZENG Xi , ZHANG Zhe-yuan , XIA Qing-qing , ZHOU Zhi-yu
Published: September 2022

Purpose: To evaluate the myocardial work (MW) changes in type 2 diabetes mellitus (T2DM) patients with or without hypertension(HT) using left ventricular pressure strain loops（LVPSL）, and to find independent related factors of MW parameters.
Methods: 40 T2DM patients, 38 T2DM patients with HT and 35 controls were enrolled. The differences between clinical data, conventional ultrasound parameters and MW parameters were analyzed among the three groups.
Results: The global longitudinal strain (GLS) of T2DM group and T2DM+HT group was lower than controls (P＜0.05). The global work index (GWI) and global constructive work (GCW) in T2DM group were lower than other groups (P＜0.05). T2DM+HT group had higher global work waste (GWW) and lower global work efficiency (GWE) (P＜0.05). Systolic blood pressure (SBP), glycosylated hemoglobin (HbA1c), duration of D2DM and pulse pressure (PP) were independent related factors of GWI, while SBP, HbA1c, duration of T2DM and diastolic blood pressure (DBP) were GCW. SBP and HbA1c were independent factors of GWW, HbA1c and duration of HT were independent factors of GWE.
Conclusion: LVPSL can recognize left ventricular subclinical systolic dysfunction early in patients with T2DM. SBP and HbA1c are two factors that have a considerable impact on MW parameters. GWE may be the best predictor of the left ventricular systolic function in the MW parameters. The impact of afterload on MW parameters should be paid more attention.
Prevalence and antibiotic resistance profile of Salmonella spp. in broiler carcasses from dominant poultry production areas in Bhutan
Authors: Penjor Kinley , Gurung Monu , Islam Kamrul , Magalhaes Ricardo J. Soares
Published: September 2022

Background: Salmonella is an important zoonotic pathogen and its infections are considered among the most commonly and widely distributed food-borne illness reported worldwide. Poultry products have been identified as important sources of Salmonella infection to humans. While there have been reports of high prevalence of Salmonella and multidrug resistance in imported chicken meat in Bhutan, the safety of nationally produced broiler meat with regards to Salmonella contamination is not known. In the absence of national surveillance of Salmonella in food animals in Bhutan, this study assessed the prevalence of Salmonella and its serotypes in broiler chicken carcass in the dominant poultry production areas of the country and determine its antibiotic susceptibility patterns.
Methods: A cross-sectional study was conducted in January to April 2016 in all five major commercial broiler meat producers and suppliers in Bhutan located in the Samphelling and Darla gewogs. Following a systematic random sampling method, 36 broiler carcasses were sampled from each of the five broiler commercial farms producing the total sample size of 180 samples. Salmonella was isolated and identified following the International Organization for Standardization methods (ISO 6579:2002). All Salmonella isolates were subjected to antibiotic susceptibility testing (AST) following the procedures of the Clinical and Laboratory Standards Institute (CLSI) method.
Results: The overall prevalence of Salmonella in broiler chicken meat samples was 12.78% (95% CI, 10.98 – 14.58). The prevalence of Salmonella spp. was higher in farms of the Samphelling gewog compared to Darla gewog [14.81% (95% CI, 8.2.7 – 21.5) vs 9.72% (95% CI, 2.9 – 16.6) respectively]. Among 23 Salmonella isolates, the most prevalent serovar was Salmonella ser. Typhi (73.9%). The Salmonella isolates showed high sensitivity to gentamicin (73.9% of isolates) followed by streptomycin (56.5%) and ampicillin (47.8%). The highest proportion of resistance was noted to tetracycline (95.6%), trimethoprim (86.9%), amoxicillin (65.2%), and ampicillin (47.8%). Among 23 Salmonella isolates, 60.87% (n=14) were considered multidrug resistant and 7 patterns of multidrug resistance were discovered.
Conclusion: The estimates of Salmonella prevalence and multidrug resistance in nationally produced commercial broiler chicken carcasses from the two main broiler meat producing areas in Bhutan, raises significant public health concerns highlighting the need for an integrated national Salmonella surveillance program across the poultry market chain.
The effect of shariah board characteristics, risk-taking, and maqasid shariah on an Islamic bank’s performance
Authors: Sueb Memed , Prasojo  , Muhfiatun  , Syarifah Lailatis , Nur Anggara Putra Rosyid
Published: September 2022

Shariah supervisory boards are a key feature of shariah governance (SG), providing additional monitoring and oversight. A suitable SG mechanism enhances risk mitigation and improves Islamic bank (IB) performance without violating shariah principles. This study examines the impact of the shariah supervisory board (SSB), maqasid shariah, and risk-taking on Islamic bank performance globally. Quantitative research design with a Dynamic panel regression approach is used with a two-step generalized method of moments (GMM) with data from the Bankscope database for 2014–2018. The findings of this study show that characteristics of SSB and risk-taking have a significant impact on IB performance. This study proves that higher SSB characteristics in terms of size, expertise, level of education, cross-membership and reputation encourage the better performance of Islamic banks. Higher risk-taking illustrates that Islamic banks are more efficient, resulting in better financial performance. Compliance with maqasid sharia indicates that sharia banks comply with Islamic laws so that the resulting performance meets financial aspects and sharia principles. SSB functions as a monitor for Islamic banks so that they operate according to sharia principles, which are reflected in the maqasid sharia elements. Therefore, a higher quality SSB and a higher maqasid shariah index score positively affect the financial performance of IBs.
Discovery and Activity Evaluation of the Inhibitory Effect of Four Kinds
of Traditional Chinese Medicine Extracts on the CYP3A4 Enzyme
Authors: Ai Chenyang , Miao Xinxin , Wang Lili , He Jun
Published: September 2022

Background and Objective:

Traditional Chinese medicines that have inhibitory effects
on the CYP3A4 enzymes were screened and their inhibitory effects were verified with in vitro bioassay.

Methods:

The computer virtual screening methods, including the CYP3A4 enzyme pharmacophore
model and the molecular docking method, were used to rapidly screen the potential CYP3A4 inhibitors
in the Traditional Chinese Medicine Database (TCMD), and then in vitro experiments were
conducted to validate the computational data.

Results:

A total of 413 chemical components in TCMD that have potential inhibitory effects on the
CYP3A4 enzyme were screened, and four kinds of traditional Chinese medicines (Abrus precatorius,
Andrographis paniculata, Angelica pubescens f.biserrata and Lithospermum erythrorhizon) contained
the most potential CYP3A4 inhibitors; The results of the in vitro experiments showed that
these four traditional Chinese medicine extracts all had certain degrees of inhibition on the CYP3A4
enzyme, with IC50 values of 5.15, 14.97, 15.2, and 24.21 μg/ml, respectively.

Conclusion:

The extracts of Abrus precatorius, Andrographis paniculata, Angelica pubescens f.
biserrata and Lithospermum erythrorhizon had certain inhibitory effects on the CYP3A4 enzyme,
and attention should be paid to the possible adverse reactions when they were used in combination
with the CYP3A4 enzyme-substrate drugs. A combination of computational approaches might be a
useful tool to identify potential inhibitors of the CYP3A4 enzyme from traditional Chinese medicine.
Therapeutic Peptides: Unravelling Conformational Dynamics by Systematic Application of Biophysical Techniques
Authors: Prabhu Arati , Pise Nikita , Raheja Radhika , Dhala Illham
Published: September 2022

Peptide therapeutics represents one of the fastest-growing sectors in the pharmaceutical
drugs pipeline, with an increasing number of regulatory approvals every year. Their pharmacological
diversity, biocompatibility, high degree of potency and selectivity make them an attractive choice in
several therapeutic areas, such as diabetes, cancer, immune, metabolic, cardiovascular and infectious
diseases. However, the development of peptides as drugs presents its own set of challenges, necessitating
extensive property optimization aimed at improving their drug-like properties and stability in biological
environments. The discovery and development of innovative peptide therapeutic platforms entail
the employment of several biophysical techniques, which monitor the structural as well as the functional
integrity of peptides. Small structural changes of the bioactive peptides in response to the presence
of various excipients can have a major impact on their pharmaceutical prowess, necessitating the
use of analytical techniques for efficient quality control during development. Here we present some
widely used methods, such as circular dichroism, fluorescence spectroscopy and multi-dimensional
homo and heteronuclear nuclear magnetic resonance spectroscopy that form an integral part of therapeutic
peptides development. The application of combination biophysical platforms ensures the
maintenance of the appropriate folded structure, which is a prerequisite for the safety and efficacy of
peptide pharmaceuticals.
Gut Microbiome Alterations in Men Who Have Sex with Men-A Preliminary
Report
Authors: Zhang Zhihua , Lu Xiaoyan , Zhang Kexin , Wang Tianli , Zhang Xueqing , Zhang Jianghui , Wei Hongyuan , Gao Pan , Wang Jun , Zhang Hongbo
Published: September 2022

Background:

Studies have found that HIV is mainly transmitted through the mucosal
surface, and the entrance of early progression of the disease is the rectal and colonic mucosa. So,
this paper aimed to explore and analyze the structural differences of gut microbiome between men
who have sex with men (MSM) and those who don’t have sex with men (Non-MSM), expecting to
find novel biological factors that potentially impact transmission and/or disease in MSM population.

Methods:

We collected a total of 33 stool samples, 16 were MSM and 17 were Non-MSM. The 16S
rRNA gene amplification sequencing was used to detect the alteration and structure of the gut microbiome
community in two groups.

Results:

The difference in β diversity of gut microbiome of two groups of subjects was statistically
significant (P<0.001), indicating that the difference in the structure of the gut microbiome of two
groups was statistically significant. Compared with the phylum and genus level of Non-MSM
group, the relative abundances of Actinobacteria, Proteobacteria, genera Collinsella, Prevotella,
Bifidobacterium and Ralstonia in MSM group were higher (P<0.001, P<0.05, LDA score
(log10)>2), and the relative abundance of Bacteroidetes, genera Erysipelotrichaceae incertae sedis,
Bilophila, Holdemania, Clostridium XIVb and Bacteroidaceae in MSM group were lower (P<0.01,
LDA score (log10)>2).

Conclusions:

There are some differences in the structure of gut microbiome between MSM group
and Non-MSM group. It indicates the differences in behavior and characteristics between MSM and
Non-MSM populations may be related to the difference in the structure of gut microbiome.