bluuebunny/crossref_metadata_2025 huggingface dataset:
Biomarker Signatures to Monitor Alcohol Consumption and Induced Organ Damage
Authors: Liji Joy M , Varghese PR , Jacobinnah Susheela , Kuttichira Praveenlal
Published: April 2021

The difficulty to differentiate long duration alcoholic behaviours is a major obstacle in the diagnosis and its treatment. Biomarkers in alcoholism are indicative of recent alcohol consumption or alcohol-induced organ damage. They are broadly divided into two; state markers, which are tools indicative of acute or chronic alcohol consumption, and trait markers, which are markers indicative of a genetic predisposition responsible to develop alcohol dependence. This review aimed to sensitise the practitioners on different alcohol state markers available now-a-days. An electronic search in Google Scholar, MEDLINE, and PubMed was conducted by using following keywords: Alcohol biomarkers, State markers, Trait markers, Alcohol consumption test. Studies on alcohol biomarkers published in English language were included in this review. Reviews and studies with free access to only abstract have been excluded. The state markers mostly used to identify chronic alcohol exposure are the Gamma-Glutamyltransferase (GGT), Aspartate and Alanine Aminotransferase (AST and ALT) which are routine serum liver function panels and Mean Corpuscular Volume (MCV) which is a haematological marker. The available non-conventional state biomarkers are Phosphatidylethanol (PEth), Fatty Acid Ethyl Esters (FAEE) and 5-Hydroxytryptophol (5-HTOL). The novel state markers which have been developed in recent research context are still awaiting validation and possible introduction to commercial settings are Plasma Sialic Acid Index of Apolipoprotein J (SIJ), Total Serum Sialic Acid (TSA), Acetaldehyde, Acetaldehyde adducts, anti-adduct antibodies and β-Hexosaminidase. Conventional alcohol biomarkers are routinely used in clinical practice. Non-conventional biomarkers seem to be promising for its estimation. Novel biomarkers are at various stages of research and development.
Immunohistochemical Expression of HER2/neu, Ki-67 and MUC1 in Benign and Malignant Gall Bladder Lesions and its Association with Clinicopathological Parameters
Authors: Roshdy Rania G , Rashad Heba M , Ibrahim Enas
Published: April 2021

Introduction: Gall Bladder Carcinoma (GBC) is a diagnostic and a therapeutic challenge. Although it is increasing, chronic cholecystitis remains the most worldwide gall bladder lesions, harbouring many epithelial changes that may end in carcinoma. Aim: To investigate the expression of HER2/neu (Human Epidermal Growth Factor Receptor 2), Ki-67 and MUC1 (Mucin 1) in malignant and non-malignant gall bladder lesions, and to evaluate its relation with clinicopathologic parameters of GBC. Materials and Methods: This retrospective study included 40 cases of GBC, eight cases of gall bladder dysplasia, 10 cases of gall bladder metaplastic changes and 25 cases of chronic cholecystitis as a control group. The blocks were collected from the Department of Pathology of Benha University Hospital, from January 2012 to December 2019. Immunohistochemical staining results of HER2/neu, Ki-67 and MUC1 were analysed and correlated by Statistical Package for the Social Sciences (SPSS) version 16 and Chi-square test or Fisher’s-exact tests. Results: Positive HER2/neu expression (+2, +3) was detected in 47.5% (19/40) of malignant cases and 12.5% (1/8) of dyspastic group, at the same time it was completely absent in the metaplastic and cholecystitis cases (p<0.01). Similarly, Ki-67 Labeling Index (LI) (≥20%) expression was found in 55% (22/40) of malignant group, while it was completely absent in the other three studied groups. All cases of malignant group 100% (40/40), 50% (4/8) of dysplastic one, one case of metaplastic (1/10) showed cytoplasmic expression of MUC1, at the same time it was completely absent in control group (0/25) (p<0.01). High MUC1 expression was found in 75% of both malignant (30/40) and dysplastic (6/8) studied cases and only one case (10%) of metaplastic group (p<0.01). There was a significant correlation between MUC1 expression and studied parameters of GBC. Conclusion: HER2/neu, and Ki-67 are overexpressed in GBC cases compared with control and dysplastic group. The study also highlights that MUC1 would be a better marker of malignant transformation of gall bladder epithelium and its depolarised expression would be reliable for detection of invasive carcinoma, so a new therapeutic agent can target these cell surface adhesion molecule (MUC1). HER2/neu can be considered as a candidate for targeted therapy in GBC treatment strategy.
Efficacy of D-Dimer Assay in Pulmonary Venous Thromboembolism: Study of 76 Cases
Authors: Saxena Shubhi , Saxena Nishant , Jain Richa , Jasani Jasmin
Published: April 2021

Introduction: Venous Thromboembolism (VTE) encompasses a wide spectrum consisting predominantly of deep venous thrombosis and pulmonary embolism. The value of Fibrin Degradation Product (FDP) of which, most common is D-dimer which is most commonly deployed to pre-diagnose venous thrombosis. Diagnosing it has always been a hard effort. It is produced when cross-linked fibrin is broken down; among patient who is suspected of having pulmonary embolism, blood D-dimer levels correlate with the probability of having pulmonary embolism. Aim: This study was done to analyse the sensitivity of plasma D-dimer for VTE. Materials and Methods: Retrospective case study of 76 patients with VTE in form of pulmonary embolism done at the Dhiraj Hospital, Sumandeep Vidyapeeth Deemed University, Vadodara from January 2019 to January 2020 for a period of one year. Prethrombolytic plasma was withdrawn and D-dimer quantification were measured using fully automatic stago coagulometer instruement (STA Compact Max). Sensitivity, Specificity, Negative Predictive Value (NPV) and Positive Predictive Value (PPV) was calculated and formulated in tables and graphs. Results: The sensitivity, NPV, specificity and PPV of the D-dimer was 95.65%, 76.92%, 66.66% and 92.95%, respectively. CT pulmonary angiography had a specificity of 80%, sensitivity of 92.75%, a NPV of 70.58% and a PPV of 95.52%. Conclusion: D-dimer is mostly the go to test for ruling out VTE especially pulmonary embolism, if the pre-test probability is intermediate. Rationale use of this test does help in prognostification and helps to achieve therapeutics faster and more effectively.
Long COVID Syndrome Following Infection with SARS-CoV-2- A Devastating Influence on Health Status in Some Affected Individuals
Authors: Soni Sarthak Nilang , Nimbalkar Somashekhar Marutirao
Published: April 2021

Almost a year since the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) began causing COVID-19, our knowledge about its manifestations continues to expand. As more people become fatally ill with COVID-19, it is now clear that many patients who developed a mild illness, recovered from a serious illness, or had an asymptomatic infection are also beginning to suffer from a newly described entity called Long COVID. Studies show that show COVID-19 influences the cardiovascular framework, yet the general effects stay obscured. Impaired diffusion capacity, lower respiratory muscle strength, and lung imaging abnormalities are seen in COVID-19 patients in the early recovery stage. As compared to non-severe cases, severe patients had a higher incidence of Diffusion capacity of lung for carbon monoxide (DLCO) impairment and are more prone to total lung capacity decrease and 6-Minute Walk Test (6MWT) decline. The degree and seriousness of long-term well-being outcomes remain unclear, yet increasing information points in the direction of poorer physiological outcomes. Long-term sequelae of COVID-19 will have enduring implications on those afflicted’s physical, mental, and social health while having a substantial monetary impact on society.
EVALUATION OF EFFLUX PUMP ACTIVITY AND BIOFILM FORMATION IN MULTIDRUG RESISTANT KLEBSIELLA PNEUMONIAE ISOLATES IN TANTA, EGYPT
Authors: El-Banna Tarek El-Said , Sonbol Fatma Ibrahim , El-Dawy Heba M , Al-Madboly Lamiaa A
Published: April 2021

Nosocomial and community acquired infections that caused by multidrug-resistant (MDR) Klebsiella pneumoniae isolates are widespread recently resulting in high morbidity and mortality due to limited number of treatment options with effective antibiotics. The aim of this study is to evaluate the antibiotic resistance profile, biofilm formation and efflux pump activity of MDR K. pneumoniae isolates collected from different hospitals in Tanta, Egypt. A total of 70 K. pneumoniae isolates characterized by standard biochemical tests and confirmed by MALDI-TOF/MS were screened for antibiotic susceptibility, efflux pump activity and biofilm formation. Isolates displayed high resistance to penicillins, cephalosporins, trimethoprim-sulfamethoxazole and the majority of tested fluoro/-quinolones and decreased resistance to imipenem, amikacin, chloramphenicol, tigecycline and colistin. Out of 70 K. pneumoniae isolates, 2 isolates exhibited Pan Drug-Resistance (PDR) profile while 57 (81.4%) and 11 (15.7%) exhibited MDR and Extensively drug-resistance (XDR) profiles, respectively. Sixty-four (91.4%) isolates exhibited efflux pump activity while all tested isolates had the ability to form biofilm with varied degrees as 40 (57.1%), 26 (37.1%), and 4 (5.7%) isolates were strong, moderate and weak biofilm producers, respectively. Also, a strong relation between efflux pump activity and biofilm formation per isolate was detected. In conclusion, Multidrug resistance, biofilm formation and efflux pump capabilities in K. pneumoniae have serious public health implications in the management and control of infections caused by this bacterium. Therefore, a multifaceted approach and precise planning are recommended in controlling these infections
REJUVENATION OF SKIN BY PREPARED CITRUS AURANTIUM, LYCOPERSICON ESCULENTUM, SANTALUM ALBUM AND PRUNUS DULCIS HERBAL FACE MASK: FORMULATION AND EVALUATION
Authors: Tripathi Devika , Mishra Sangeeta , Sahoo Jagannath , Sharma Dinesh Kumar , Rai Awani Kumar , Wal Pranay
Published: April 2021

The main objective of the work is the formulation and evaluation of a natural herbal face mask for rejuvenation and glowing skin from locally available ingredients. Citrus aurantium, Lycopersicon esculentum, Santalum album, Prunus dulcis, Rose petals, Camellia sinensis leaves were procured from the local market and were dried, powdered, then passed through sieve no-100, mixed geometrically, and packed in an airtight container for converting into unique formula. The distinguishing microscopically characters of individual powders were noted, and quantitative measurements were taken. The powder had passable flow property which is suitable for a face mask. The particle size of the powder was found to be 20 -25µm. Herbal face mask is used to stimulate blood circulation, rejuvenates the muscles and help to maintain the elasticity of the skin and remove dirt from skin pores and provide glow and flawless skin. The non-toxic nature reduced allergic reactions and easy availability of herbs making them acceptable and useful for users.
Non-Invasive Rapid Method to Evaluate Tunisian Virgin Olive Oil Based on color Measurement by Digital Images and Chlorophyll-Carotenoids Content
Authors: Fendri Mahdi , Mhamdi Sawssen , Jendoubi Fadwa , Larbi Ajmi
Published: April 2021

Color and pigment analyses are not required by the majority of olive oil marketing standards. However, it is a basic attribute that is highly associated, by most consumers, with the idea of quality. In this study, we aim at providing a fast non-invasive method for routine analysis that can be used on a large scale in the laboratories of olive oil analysis starting from pigment quantification and color range measurements. A selection of 172 virgin olive oil samples obtained in Tunisia between 2018 and 2019 were used for this purpose. Chlorophyll and carotenoid contents were analyzed using a UV spectrophotometer standard method while color range was measured using digital images taken under controlled conditions. All samples showed high significant differences in chlorophyll and carotenoid contents (p <0,01) confirming that the visual selection of the set of samples was satisfactory for this study. Chlorophyll content varied from 3,0 to 28,3 ppm for samples SM137 and SM96 respectively, while carotenoids ​​oscillated between 0,7 and 6,2 ppm for SM138 and SM100 respectively. Principal component analysis using chlorophyll and carotenoids contents along with RGB-CYMY color measurements showed a higher significant correlation P<0,05 between pigment contents and Red, Green, Blue and Yellow colors. Bivariate tests suggest that although color and pigments are correlated, color range assessment using digital imaging may represent a more sensitive method to discriminate olive oil according to cultivar, geographical origin, maturation index and year of harvest.
The Effect of Corporate Social Responsibility, Working Capital Efficiency, Earning Per Share on Company Performance and Mining Company Value 2019-2020
Authors: Suwandi .
Published: April 2021

This study aims to determine the effect of CSR, Working Capital Efficiency, EPS on company performance and value of mining companies in 2019-2020. The approach in this study uses a quantitative approach with research methods using non-participant observation. The population in this study are consumer goods companies listed on the IDX. The number of samples in this study was 12 samples registered on the IDX in 2013-2017. The data analysis technique used is in the form of path analysis and classical assumption and Sobel Test. Based on the research results, it is found that CSR has a positive effect on firm value. The results showed that the value of the original sample estimation of CSR on PBV was 0.251 with a significance below 5% which was indicated by the t-statistics value of 3.667 which was greater than the t-table value of 1.962. Then, in testing the effect of CSR on company performance, it was found that the original sample estimate value of CSR on ROA was not the effect of CSR on company performance. So that there is no effect of CSR on company performance. Furthermore, in testing the effect of EPS on firm value, it is found that there is an effect of EPS on firm value. In testing the effect of EPS on company performance, it is found that there is an effect of EPS on company performance. Furthermore, it is also found the influence of WCE on firm value. The influence of WCE on firm value was also found to have a significant effect.
Proficiency, Attitudes, and Practices in Breastfeeding of Participants in a Pediatric Congress
Authors: Silva Cynthia Francisca Xavier Costa de Assis , Melo Maria do Carmo Barros de , Chaves Roberto Gomes , Bouzada Maria Cândida Ferrarez
Published: April 2021

Objective: To investigate the proficiency, practices, and attitudes about breastfeeding of participants in a Pediatrics Congress.
Methods: Cross-sectional study in which an online questionnaire was applied, using a specific QRcode, for each study participant, in June 2018. The questions were formulated according to the World Health Organization (WHO). Among the 39 questions, 13 identified the profile of the participants, 19 questions assessed the proficiency in breastfeeding and 7 questions the practices and attitudes.
Results: Responses to 296 questionnaires were evaluated, 62.5% of which were health professionals and 37.5% were undergraduate health students. In assessing proficiency, the global average did not reach the expected minimum of 70%. But the highest proficiency averages were found among health professionals (p: 0.0136), among professionals with more recent degrees (p <0.0001), and those who performed most of their activity in the public sector (p: 0.018). 77% of health professionals and 73% of students assessed attitudes and practices about breastfeeding as appropriate.
Conclusion: The low proficiency in the population studied points to the need for periodic training of professionals in breastfeeding and greater emphasis on undergraduate curricula in the health area on the subject.
Evaluation of Rural Entrepreneurship with Value Added Regram (Cajanus cajan) Using Mini Dal Mill
Authors: Jahan Afifa , Arunjyothi R. , Reddy M. Jagan Mohan , Reddy T. Prabhakar , Shankar A. , RamaKrishna K. , Rajasheker B. , Shravika L. , Rajasheker M.
Published: April 2021

Pulses processing is a very huge business in India. In India, split of pulses are prepared called as “Dal” or “Dhal”. Regdram cultivating farmers are demotivated as there net returns are low due to continuous market fluctuation in prices of Redgram and this is becoming the reason for decrease in area of cultivation under Redgram. Milling pulses improves bio-availability of nutrients and Partial or complete removal of antinutritional and toxic compounds making it nutritive for human consumption. Mini dal mill is low investment enterprise to improve the net income of farmers. The present study concluded that the average gross income through sale of Redgram is Rs 41.3/KG without processing and Rs 63/KG with processing. The profitability is more with the processing of Redgram. The cost benefit ratio is 1:1.18 without processing and 1:1.80 with processing. Hence farmers must be educated to develop entrepreneurship and promote value added Redgram using mini dal mill.
Pattern of Lower Limb Doppler Ultrasonography Requests and Findings in a Tertiary Institution in Makurdi; North-Central Nigeria
Authors: Msuega Chia Daniel , Terkimbi Annongu Isaac , Mohammed Hameed , Iorpagher Kator Paul , Aliyu Abdullahi
Published: April 2021

Background: Doppler ultrasound scan (DUS) is a valuable, cost effective, and relatively rapid diagnostic technique that provides a non-invasive assessment of the vascular circulation in the lower limb.

Aims: To determine the pattern of lower limbs Doppler requests in our environment and to evaluate the Doppler findings.

Study Design: Retrospective study

Place and Duration of Study: Radiology department of Benue state university Teaching Hospital over a one-year period from January 2018 to December 2018.

Methods: We included 200 patients that had lower limb Doppler ultrasound for various indications. Data on age, gender, indications and findings was retrieved from departmental cards and case notes, then collated and analyzed using SPSS software version 23, with the P value taken as =.005.

Results: Two hundred patients were scanned;106 males and 94 females with age range of 10-109 years. Their mean age was 34.2 ±13.5 years. Most patients 48(24.0%), who presented for Doppler sonography of the lower limb had diabetic foot ulcer (DFU), followed by left leg swelling in 42(21.0%) patients. DVT alone was indicated in 33(16.5%) patients. Both DFU and DVT were more in the male patients with a M:F ratio of 26:22 and 21:12 respectively. The indications for lower limb doppler ultrasound scan are seen to generally increase with increasing age, with the least among those less than 40years 32(16.0%) and highest among the greater than 60years age groups 89(44.5%). At doppler ultrasound, there are more patients with Deep vein thrombosis (DVT) 104(52.0%). Normal study and peripheral vascular disease (PVD) have equal incidence respectively in 48(24%) of the patients. DVT and PVD were more in the male group with a M: F ratio of 55:49 and 27:21 respectively while normal studies were seen equally in both sexes (M: F=24:24).

Conclusion: Doppler ultrasound has been shown to be a cost-effective and valuable non-invasive tool for the diagnosis of lower limb vascular diseases.
Pattern of Use Unlicensed Medication in Pediatrics: A Retrospective Study at Major Tertiary Care Hospital in Saudi Arabia
Authors: Alolayan Abdulaziz , Almansour Basil , Barnawi Yasmin , Munawar Husam , Almodamegh Saad , Aldossari Huda , Mansy Wael
Published: April 2021

Background: Unlicensed medication use (off label use) is common in pediatrics practice. There are more than 75% of drugs which approved for using in adults, data of efficacy and safety in pediatric population is not completely available, and missed data might be due to some reasons mainly ethical consideration. Our study aimed to assess practicing of using of unlicensed medication in pediatrics at major tertiary care hospital in Saudi Arabia.

Methods: A retrospective review of pediatrics prescriptions that were prescribed as unlicensed medication use by collection of all unlicensed use forms that known as form B which approved by pharmacy and therapeutics (P&T) committee at Prince Sultan Military Medical city (PSMMC). Data collection stared from January 2018 until the end of 2020. Children up to 14 years of age and administered at least one medication were eligible to participate in the study.

Results: The total collected off label prescriptions (both in and out patients) was 128 from January 2018 till end of 2020. Prescription for females were 39.84% while their male counterparts were 60.16%. Ophthalmology, Oncology and both Otorhinolaryngology and general pediatrics were the most frequent specialties prescribed unlicensed medications by 34.38%, 19.53% and 8.59% respectively. Overall, unlicensed medicine use was highest (33.6%) for products belong to monoclonal antibodies class. Surgical intervention was the commonest indication for using unlicensed medication (35.94%) followed by infectious diseases treatment (14.06%). Represented as the cumulative off-label frequency percentage, the most common reason of off-label use was by indication (35.94%), frequency (33.18%), Dose (19.82%), while for the route was almost (11.06%). The highest frequency of off label prescriptions according to pharmacological class split by gender and age category showed significance level of 0.045 in males and 0.001 in infants respectively.

Conclusion: Class variability of unlicensed medications in this study, sought us to confirm that physician using this therapeutic option yet ethically, but in a disorganized manner. Thus, prescribing unlicensed drugs specifically in pediatric needs to be better validated by current and new evidence. The findings of this study call for further research across the kingdom to start off label legislation process under SFDA authority. Current off-label dosage amounts pose concerns about drug safety exceptionally in children.
Detecting the Disease before it’s Too Late
Authors: Utkarsh .
Published: April 2021

Specific trials or examination exists in detecting deadly diseases. Various facilities are provided these days for determining many chronic diseases, like in detecting cancer, tuberculosis, keratin level (dialysis), coronary artery disease, etc.   But delaying in diagnosing emergency cases which need very quick action will lead to adverse situations. The process of this early detection of disease starts with a special test and further process depends on the special test result whether it is positive or negative. The sad reality of modern technology in the medical industry is that there is very less availability of vanguard doctors, who can help patients in diagnosing their disease, which can be treated successfully as soon as possible diagnosis has been done. Therefore, Hong Kong University (HKU) scientists discovered “Biomarker” which is being rapidly used by physicians, Neuroscientists and epidemiologists in measuring the intensity of disease provided with the details of its cause and treatment. Biomarkers possess possibilities in making wishes of doctors and scientists into reality, to identify that person who is at high risk of any disease so that doctors can take protective measures in saving that life within time. Nevertheless, according to Global data “Biomarkers” are a useful instrument in examining COVID-19 vaccine and fastening the process of clinical trials, decreasing the development cost and decreasing patient security risk. They also can be utilized to find the drug which can help in treating Covid-19 patients and can also be used to determine which drugs might be able to treat COVID-19 patients.
Prevalence of Cardiovascular Disease Risk Factors among People in Hail City, Saudi Arabia
Authors: Shahin Mona Madbouly Mohammad , Mahmoud Madiha Rabie , Al-Shmaily Hanan Odah Salem , Altamimy Salma Rshed Mohammed , Alanzi Lama Abdulaziz Saud
Published: April 2021

Background: Cardiovascular diseases (CVDs) are the number one cause of death globally, and representing 31% of all global deaths according to WHO. So, this study may be useful to detect the risk factors of CVDs and how to prevent them to help in reducing the rate of deaths due to these diseases.

Aim: To estimate the prevalence of CVD risk factors in Hail region, Saudi Arabia (KSA).

Methods: The study was carried out through an observational cross-sectional study on 300 participants from Hail region including both genders (females 231 [77%] & males 69 [23%]) with age group range from 18 years-old and above. The study was conducted using an electronic questionnaire, and the data was analyzed using Software Statistical Package for the Social Science (SPSS) version 23.

Results: The highest risk factor for CVDs was obesity, the total number of overweight, obese and extremely obese was 171 (57%) which was more pronounced with peoples at the age of 31-45 years old. Other risk factors that were found in our participants were hypertension (8.3%), diabetes mellitus(DM, 7.3%),family history of diseases (80.4%), consuming insufficient amounts of fruits and vegetables (62.7%), always drinking coffee (60.9%), physical inactivity (34.7%), consuming fast foods more than one time per week (32.4%) and smoking 10.3%.We can conclude that many risk factors for CVDs were prevalent among Hail population either non modifiable (family history of diseases) or modifiable (obesity, physical inactivity, fast foods, insufficient amounts of fruits and vegetables) showed a considerable percentage which needs awareness programs for Hail population.
The Neuroscience behind the Mechanism of Placebos: Placebo Effect
Authors: Sharma Preksha
Published: April 2021

The science behind any kind of medical treatment is oriented around the effects of the psychology of humans with the corresponding therapeutic mechanism of the treatment. The human mind and its psychology is always an interesting and complex matter of discussion for researchers. The human mind is so powerful that it is even capable of healing the mental and physical health of the human body. To study this psychological concept of a healing mechanism, the Placebos effect is studied. This paper discusses the placebo effect and the physiology neuroscience involved in the whole concept of the Placebos and its mechanism. Because the placebos and its mechanism are so powerful that it is capable of even manipulating the human mind and the body as well the study discussed all the facts in an evidential manner.
Haemopoietic Potential of Tannin Fractionates of Vitex doniana Leaf on Nitrosobis (2-Oxopropyl) Amine Comobidity in Docetaxel-Induced Myelosuppression in Wistar Rat
Authors: Anyanwu Godson Emeka , Abireh Ifeanacho Ezeteonu
Published: April 2021

Aim: This study investigated the haemopoietic potential of tannin fractionate of Vitex doniana leaf against nitosobis (2-oxopropyl) amine comorbidity in docetaxel-induced bone marrow suppression.

Study Design: This is an experimental research.

Place of Research: University of Nigeria, Enugu campus.

Methodology: The male Wistar rats used in this experiment were twenty-eight in number, and they were grouped into 7, with each group having four rats. Group 1 served as control, and received 1ml of normal saline, while groups 2-7 were treated with Nitrosobis (2-oxopropyl) amine 5 mg/kg daily for 2 weeks. Then groups 3-7 were treated with 8 mg/Kg of docetaxel weekly for 2 weeks. And groups 4, 5 and 6 also received 250 mg/Kg and 500 mg/Kg and 1000 mg/kg of tannin, respectively, daily for 2 weeks. Group 7 received 40 mg/Kg of fesolate daily for 2 weeks.

Results: The haemoglobin concentration and white blood cell count of rats in the groups treated with Nitrosobis (2-oxopropyl) amine alone (group 2) and Nitrosobis (2-oxopropyl) amine plus Docetaxel (group 3) showed statistically significant reduction (p=.05) in number when compared with the group treated with normal saline (group 1). The haemoglobin concentration and white blood cell count of the rats in the groups treated with 250 mg/kg, 500 mg/kg, and 1000 mg/kg of the tannin fractionate, in addition to the Nitrosobis (2-oxopropyl) amine and Docetxel (i.e. groups 4, 5, and 6, respectively) showed statistically significant dose dependent increase in number, with the group treated with 1000mg/kg showing the highest increment (p=.05). The cells in the bone marrow show significant reduction in number in the rats treated with Nitrosobis (2-oxopropyl) amine (group 2) and Nitrosobis (2-oxopropyl) amine plus docetaxel (group 3) when compared with the rats in group 1 (treated with normal saline). With the addition of graded doses of the tannin fractionate, 250 mg/kg, 500 mg/kg, and 1000mg/kg (i.e. groups 4, 5, and 6, respectively), the number of cells in the bone marrow showed statistically significant increase when compared to group 3 (treated with Nitrosobis (2-oxopropyl) amine plus docetxel), with the rats in the group treated with 1000 mg/kg of tannin fractionate (group 6) having the highest increment (p=.05).

Conclusion: Tannin obtained from Vitex doniana leaf extract increases the haemoglobin concentration in dose dependent manner. It also increases the white blood cell count, and number of proliferating bone marrow cells, following suppression by Nitrosobis (2-oxopropyl) amine and Docetaxel. So, this tannin obtained from Vitex doniana leaf extract may be useful in clinical practice to cushion the myelosupression, anaemia and leukopenia that are associated with use of docetaxel in treatment of malignancies.
Programmable Self‐Locking Micromachines with Tunable Couplings
Authors: Chen Qianying , Huang Tian-Yun , Lv Pengyu , Huang Jianyong , Duan Huiling
Published: April 2021

Intelligent micromachines that perform tasks in complex microenvironments by adjusting structural configurations and physical properties offer substantial potential for use in many fields, including precision medicine, microfluidic channels, micromanipulations, and bioengineering. Recent progress in smart materials and 4D microprinting provides a feasible strategy for fabricating compound micromachines by designing and assembling predictable 3D‐to‐3D shape‐morphing components. However, shape transformations of these components can only be triggered simultaneously by external stimuli, and orderly triggering among them cannot be achieved yet for an intended purpose of performing more efficient actions. Herein, a novel sequentially triggered strategy is proposed for developing intelligent micromachines that consist of multiple reconfigurable components that work interactively with each other. Furthermore, self‐locking micromachines with tunable coupling mechanisms that coordinate accurate time‐sequence deformations among components are achieved. Three types of locking couplings are modulated based on finite‐element analysis (FEA)‐aided design. The proposed method provides an effective strategy to create next‐generation intelligent micromachines that can change their shapes to adapt to complex situations and complete multiple tasks.
Large granular lymphocytic leukemia – A retrospective study of 319 cases
Authors: Dong Ning , Castillo Tokumori Franco , Isenalumhe Leidy , Zhang Yumeng , Tandon Ankita , Knepper Todd C. , Mo Qianxing , Shao Haipeng , Zhang Ling , Sokol Lubomir
Published: April 2021

Large granular lymphocytic leukemia (LGLL) is a rare hematological malignancy that arises from cytotoxic T lymphocytes (T‐LGLL) in 85% of cases and natural killer (NK) cells in the rest. A significant knowledge gap exists regarding the pathogenesis, treatment choices, and prognostic factors of LGLL. We report a cohort of 319 consecutive LGLL patients who presented to our cancer center between 2001 and 2020. A total of 295 patients with T‐LGLL and 24 with chronic NK‐cell lymphoproliferative disorder (CLPD‐NK) were identified. The median age was 65 years (range, 17–90 years). Eighty‐three patients (26.0%) had autoimmune diseases. A total of 119 patients (37.3%) had coexisting malignancies, 66 (20.7%) had solid tumors, and 59 (18.5%) had hematological malignancies. Most coexisting malignancies were diagnosed before the diagnosis of LGLL. Treatment was needed for 57% of patients. Methotrexate (MTX), cyclophosphamide (Cy), and cyclosporine A (CSA) were most used and had similar response rates between 61.5%–74.4%. Cy produced more complete responses (32.3%) compared to MTX and CSA (15.7% and 23.1%, respectively). Thrombocytopenia, splenomegaly, and female gender (after controlling for autoimmune diseases) were associated with decreased response rates to MTX, CSA, or Cy. Autoimmune diseases were associated with increased response rates. Thrombocytopenia was an independent risk factor for worse survival.
Aging‐related Alzheimer's disease‐like neuropathology and functional decline in captive vervet monkeys (Chlorocebus aethiops sabaeus)
Authors: Frye Brett M. , Craft Suzanne , Latimer Caitlin S. , Keene C. Dirk , Montine Thomas J. , Register Thomas C. , Orr Miranda E. , Kavanagh Kylie , Macauley Shannon L. , Shively Carol A.
Published: April 2021

Age‐related neurodegeneration characteristic of late‐onset Alzheimer's disease (LOAD) begins in middle age, well before symptoms. Translational models to identify modifiable risk factors are needed to understand etiology and identify therapeutic targets. Here, we outline the evidence supporting the vervet monkey (Chlorocebus aethiops sabaeus) as a model of aging‐related AD‐like neuropathology and associated phenotypes including cognitive function, physical function, glucose handling, intestinal physiology, and CSF, blood, and neuroimaging biomarkers. This review provides the most comprehensive multisystem description of aging in vervets to date. This review synthesizes a large body of evidence that suggests that aging vervets exhibit a coordinated suite of traits consistent with early AD and provide a powerful, naturally occurring model for LOAD. Notably, relationships are identified between AD‐like neuropathology and modifiable risk factors. Gaps in knowledge and key limitations are provided to shape future studies to illuminate mechanisms underlying divergent neurocognitive aging trajectories and to develop interventions that increase resilience to aging‐associated chronic disease, particularly, LOAD.
Chemiluminescence Resonance Energy Transfer Efficiency and Donor–Acceptor Distance: from Qualitative to Quantitative
Authors: Lou Jinhui , Tang Xiaofang , Zhang Haoke , Guan Weijiang , Lu Chao
Published: April 2021

Since its birth in 1967, the utilization of chemiluminescence resonance energy transfer (CRET) has made substantial progress in a variety of fields for its unique features. However, the quantitative relationship between CRET efficiency and donor–acceptor distance has not yet been determined owing to the difficulty in designing the variable lengths between chemiluminescent donors and acceptors. Herein, we synthesized three kinds of tetraphenylethene (TPE)‐anchored cationic surfactants with aggregation‐induced emission (AIE) characteristics. For the first time, it is quantitatively demonstrated that the CRET efficiency is inversely proportional to the sixth power of distance between luminol donors and TPE acceptors. The details disclosed in this contribute have provided the solid evidence that CRET follows Förster resonance theory. Our strategy would build a promising platform to control donor–acceptor distance, allowing to the interdisciplinary applications of CRET.
Trifluoromethyl Hydrolysis En Route to Corroles with Increased Druglikeness
Authors: Yadav Pinky , Khoury Sally , Fridman Natalia , Sharma Vinay K. , Kumar Amit , Majdoub Mahmoud , Kumar Anil , Diskin‐Posner Yael , Mahammed Atif , Gross Zeev
Published: April 2021

Heme‐like metal‐chelating macrocycles, including expanded and contracted porphyrins, are of everlasting interest as drug candidates for numerous diseases. Still, all reported corrole derivatives (and most other heme analogues) do not fulfill the most basic standards expected for oral drug administration: a combination of low molecular weight and reasonable water solubility. We now disclose a very straightforward synthetic method that relies on surprisingly facile trifluoromethyl hydrolysis for gaining access to a new class of corroles that do satisfy all druglikeness criteria. The relevance is briefly exemplified for the iron corroles by demonstrating the ability to affect their association with plasma proteins and their performance for catalase‐like decomposition of hydrogen peroxide.
A Supported Pd2Dual‐Atom Site Catalyst for Efficient Electrochemical CO2Reduction
Authors: Zhang Ningqiang , Zhang Xinxin , Kang Yikun , Ye Chenliang , Jin Rui , Yan Han , Lin Rui , Yang Jiarui , Xu Qian , Wang Yu , Zhang Qinghua , Gu Lin , Liu Licheng , Song Weiyu , Liu Jian , Wang Dingsheng , Li Yadong
Published: April 2021

Dual‐atom site catalysts (DACs) have emerged as a new frontier in heterogeneous catalysis because the synergistic effect between adjacent metal atoms can promote their catalytic activity while maintaining the advantages of single‐atom site catalysts (SACs), like 100 % atomic utilization efficiency and excellent selectivity. Herein, a supported Pd2DAC was synthesized and used for electrochemical CO2reduction reaction (CO2RR) for the first time. The as‐obtained Pd2DAC exhibited superior CO2RR catalytic performance with 98.2 % CO faradic efficiency at −0.85 V vs. RHE, far exceeding that of Pd1SAC, and coupled with long‐term stability. The density functional theory (DFT) calculations revealed that the intrinsic reason for the superior activity of Pd2DAC toward CO2RR was the electron transfer between Pd atoms at the dimeric Pd sites. Thus, Pd2DAC possessed moderate adsorption strength of CO*, which was beneficial for CO production in CO2RR.
Single and hybrid organoclay‐filled PLA nanocomposites: Mechanical properties, viscoelastic behavior and fracture toughening mechanism
Authors: Lopes Alves Jefferson , de Tarso Vieira e Rosa Paulo , de Redondo Realinho Vera C. , de Sousa Pais Antunes Marcelo , Ignacio Velasco José , Morales Ana Rita
Published: April 2021

Poly (lactic acid) (PLA) nanocomposites based on single and hybrid organic‐modified montmorillonites were previously studied in terms of their morphological, thermal and fire performance. As surfactants of the organoclays influenced the compatibility between the nanofillers and PLA with different degrees of clay platelets dispersion, the present work investigated the effect of these features in the mechanical properties of PLA nanocomposites. PLA nanocomposites specimens were analyzed by dynamic‐mechanical‐thermal analysis, which pointed out changes in the viscoelastic behavior of the materials by the incorporation of the organoclays, namely the increase of the storage modulus due to polymer chains movements restriction and reinforcement effects associated with the dispersion of the nanofillers. Flexural and impact testing showed that hybrid organomontmorillonites containing ester ammonium and ethoxylated amine improved PLA's ductility, toughness and impact resistance. This behavior was explained by the high level of compatibility and interaction between the surfactants and PLA chains due to the polar groups in their structures. These organoclays caused a transition on PLA's fracture from brittle to ductile in a way that the toughening mechanism was explained by crazing and multi‐shear banding induced by the plasticized interfacial region around these organoclays.
Fuzzy modeling and control of a class of non‐differentiable multi‐input multi‐output nonlinear systems
Authors: Zare Kazem , Shasadeghi Mokhtar , Izadian Afshin , Niknam Taher , Asemani Mohammad Hassan
Published: April 2021

This paper presents a new approach in modeling and control of multi‐input multi‐output (MIMO) systems that have non‐differentiable operating points. A circle criterion is introduced at the non‐differentiable operating points to divide the entire operating region into two parts. Takagi‐Sugeno fuzzy models are developed in each part, and a switching framework is introduced to model the operating region. Accordingly, a sliding mode controller (SMC) is developed. The proposed modeling and controller are implemented on the benchmark quadruple tank process (QTP). It is demonstrated that the proposed modeling and controller design provides simplicity and universality in a set of nonlinear systems; it is robust with respect to various internal and external disturbances and model uncertainties which allows for accurate regulation and tracking; and it converges in finite time, is capable of controlling nonlinear systems with coupling dynamic, and enables fuzzy modeling of continuous‐time systems without imposing differentiability.
Utility of 4‐chloro‐7‐nitrobenzofurazan for spectrofluorimetric and spectrophotometric determinations of the anti‐hirsutism agent (α‐difluoromethylornithine) in pharmaceutical cream samples
Authors: Almahri Albandary
Published: April 2021

α‐Difluoromethylornithine is an effective medication for the treatment of African Trypanosomiasis and widely distributed for the treatment of hirsutism. This work provides an adequate analytical protocol for the spectrophotometric and the spectrofluorimetric determination of α‐difluoromethylornithine through its interaction with 4‐chloro‐7‐nitrobenzofurazan (NBD‐chloride) reagent. After optimization of the reaction conditions (NBD‐chloride volume, buffer volume, the best diluting solvent, heating time and temperature and pH of the medium) the reaction product was measured spectrophotometrically at λmax = 478 nm and spectrofluorimetrically at λemission = 540 nm after λexcitation = 475 nm. The proposed methods were linear over the ranges 5–30 μg ml−1 and 0.4–2 μg ml−1 for the spectrophotometric method and the spectrofluorimetric method, respectively. Moreover, the proposed work offers an adequate sensitive and selective determination for α‐difluoromethylornithine where the detection limits were 0.90 μg ml−1 and 0.071 μg ml−1 for the spectrophotometric method and the spectrofluorimetric method, respectively. Furthermore, both methods were successfully applied for the quantification of α‐difluoromethylornithine in the pharmaceutical cream samples with acceptable recovery results.
Bio‐functionalized titanium surfaces with modified silk fibroin carrying titanium binding motif to enhance the ossific differentiation of MC3T3‐E1
Authors: Watanabe Mai , Bhawal Ujjal K. , Takemoto Shinji , Nishiyama Norihiro , Nakahara Yuichi , Tatematsu Ken‐ichiro , Sezutsu Hideki , Kuwabara Nobuo , Minamisawa Tamiko , Shiba Kiyotaka , Asakura Tetsuo
Published: April 2021

Silk fibroin (SF) from Bombyx mori has superior properties as both a textile and a biomaterial, and has been used to functionalize the surfaces of various medical inorganic materials including titanium (Ti). In this study, we endowed SF with reversible binding ability to Ti by embedding a titanium binding motif (minTBP‐1 and RKLPDA). Artificial SF proteins were first created by conjugating gene cassettes for SF motif (AGSGAG) and minTBP‐1 motif with different ratios, which have been shown to bind reversibly to Ti surfaces in quartz crystal microbalance analyses. Based on these results, the functionalized SF (TiBP‐SF) containing the designed peptide [TS[(AGSGAG)3AS]2RKLPDAS]8 was prepared from the cocoon of transgenic B. mori, which accelerates the ossific differentiation of MC3T3‐E1 cells when coated on titanium substrates. Thus, TiBP‐SF presents an alternative for endowing the surfaces of titanium materials with osseointegration functionality, which would allow the exploration of potential applications in the medical field.
Oncolytic virus purification with periodic counter‐current chromatography
Authors: Mendes João P. , Silva Ricardo J. S. , Berg Mikael , Mathiasson Linda , Peixoto Cristina , Alves Paula M. , Carrondo Manuel J. T.
Published: April 2021

Virus‐based biologicals are one of the most promising biopharmaceuticals of the 21st century medicine and play a significant role in the development of innovative therapeutic, prophylactic, and clinical applications. Oncolytic virus manufacturing scale can range from 5 L in research and development up to 50 L for clinical studies and reach hundreds of liters for commercial scale. The inherent productivity and high integration potential of periodic counter‐current chromatography (PCC) offer a transversal solution to decrease equipment footprint and the reduction of several non‐value‐added unit operations. We report on the design of an efficient PCC process applied to the intermediate purification of oncolytic adenovirus. The developed ion‐exchange chromatographic purification method was carried out using a four‐column setup for three different scenarios: (i) variation in the feedstock, (ii) potential use of a post‐load washing step to improve virus recovery, and (iii) stability during extended operation. Obtained virus recoveries (57%–86%) and impurity reductions (>80% DNA, and >70% total protein) match or overcome batch purification. Regarding process stability and automation, our results show that not only the dynamic control strategy used is able to suppress perturbations in the sample inlet but also allows for unattended operation in the case of ion exchange capture.
microRNA‐377‐3p downregulates the oncosuppressor T‐cadherin in colorectal adenocarcinoma cells
Authors: Di Palo Armando , Siniscalchi Chiara , Polito Rita , Nigro Ersilia , Russo Aniello , Daniele Aurora , Potenza Nicoletta
Published: April 2021

Colorectal cancer (CRC) is the second leading cause of death of malignant tumors worldwide. Recent studies point to a role for the adiponectin‐receptor axis in colorectal carcinogenesis, and in particular to the oncosuppressive properties of the T‐cadherin receptor. In addition, the loss of T‐cadherin expression in tumor tissues has been linked to cancer progression and attributed to aberrant methylation of its promoter. Recognizing the pivotal role of microRNAs in CRC, this study explores their possible contribution to the downregulation of T‐cadherin. A systematic bioinformatics analysis, restricted by microRNA expression data in the colon or in cultured colorectal cell lines, predicted twelve top‐ranking target miRNA sites within the 3ʹ UTR of T‐cadherin. Experimental validation analyses based on luciferase reporter constructs and miRNA mimic or miRNA inhibitor transfections toward colorectal adenocarcinoma cell lines indicated that miR‐377‐3p was able to directly bind to the T‐cadherin sequence, and thus downregulating its expression. Given the oncogenic activity of miR‐377 and the oncosuppressive activity of T‐cadherin in CRC, the regulatory circuit highlighted in this study may add new insights into molecular mechanisms driving colorectal carcinogenesis, and perspectively it could be exploited to identify novel biomarkers and therapeutic targets.