bluuebunny/crossref_metadata_2025 huggingface dataset:
The Application of a Universal Assay for Identifying the Source of Fecal Contamination in Southeast Michigan Water Bodies
Authors: Jamison Megan N. , Hart John J. , Szlag David C.
Published: January 2023

Recreational water quality monitoring (RWQM) is an important tool to aid public health officials in preventing exposure to waterborne pathogens originating from fecal contamination. RWQM methods rely on fecal indicator bacteria (FIB) such as E. coli or enterococci. Unfortunately, E. coli and other FIB are not strict anaerobes and can naturalize and reproduce in the environment. These naturalized populations can be resuspended due to wave action or other disturbances, sometimes giving a false positive for fecal contamination using RWQM methods. This project implemented a universal marker or a non-host specific MST target to determine whether it could differentiate between recent fecal contamination and resuspended populations of bacteria. Five public beaches in southeast Michigan were monitored for FIB and MST. The non-host specific marker in addition to the FIB was successfully applied to determine whether elevated E. coli levels were caused by recent fecal contamination or resuspension.
Time step adaptivity in the method of Dahlquist, Liniger and Nevanlinna
Authors: Layton William , Pei Wenlong , Trenchea Catalin
Published: January 2023

Dahlquist, Liniger and Nevanlinna devised a family of one-leg two-step methods (DLN) that is second order, A- and G- stable for arbitrary, non-uniform time steps. The DLN method thus has strong potential for use in adaptive codes, but its adaptive step size selection is little explored. This report develops two approaches for the efficient local error estimation in the DLN method, and tests their use in a standard adaptivity framework. Many methods of error estimation are possible; herein we focus on two complementary estimators which involve minimal extra storage and computations. First we evaluate the local truncation error of the DLN method by Milne’s device, using the difference between the solution of the DLN method and the solution of a variable-step, explicit, second-order Adams-Bashforth-like method. Second, we use a recent refactorization of the DLN method, which eases implementation of DLN in legacy codes, to obtain an effective error estimation at no extra cost. We perform a number of numerical tests, comparing the two time adaptive DLN algorithms with some standard numerical ODE packages. Our tests indicate that the adaptive DLN method, with error estimated by Milne’s device, is an efficient and reliable method, even for stiff and unstable problems.
A Novel Clinical Prognostic Model for Breast Cancer Patients with Malignant Pleural Effusion: Avoiding Chemotherapy in Low-risk Groups?
Authors: Wang Yichen , Zhou Tao , Zhao Shanshan , Li Ning , Sun Siwen , Li Man
Published: January 2023

Malignant pleural effusion (MPE) is a severe complication in patients with advanced cancer that is associated with a poor prognosis, and breast cancer is the second leading cause of MPE after lung cancer. Herein, our study aimed to construct a machine learning-based model for predicting the prognosis of patients with MPE combined with breast cancer. We analyzed 196 patients with both MPE and breast cancer (143 in the training group and 53 in the external validation group). Least absolute shrinkage and selection operator and univariate Cox regression analyses were applied to identify eight key clinical variables, and a nomogram model was established. To facilitate the use of the model, an online web server was also created. Model performance was evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analyses. Based on the ROC curves for 3-, 6-, and 12-month survival, the areas under the curves were 0.824, 0.824, and 0.818 in the training set and 0.777, 0.790, and 0.715 in the validation set, respectively. In the follow-up analysis, both systemic and intrapleural chemotherapy significantly increased survival in the high-risk group compared to the low-risk group. Collectively, we have developed a first-ever survival prediction model for breast cancer patients with newly diagnosed MPE and validated the model using an independent cohort. The model can be used to accurately predict prognosis and guide individualized treatment.
Fetal Outcomes & Continuity in Perinatal Palliative Care Patients at a Quaternary Care Pediatric Hospital
Authors: Farmer Zachary , Palmaccio-Lawton Samantha , Flint Hilary , Whitford Brittney , Thienprayoon Rachel , Nee Krista
Published: January 2023

Objective: Perinatal palliative care (PPC) is the coordinated application of palliative care principles to the care of families, fetuses and newborns with suspected life limiting conditions. This approach relies on continuity of care that spans pregnancy, birth and beyond. The goal of this retrospective cohort study was to evaluate outcomes and PPC continuity in infants born to families who received PPC at a quaternary care pediatric hospital, and to identify targets to improve care continuity.
Study Design: PPC patients seen between July 2018 and June 2021 were identified via local PPC registry. Demographic, outcome, and continuity data were gathered from the electronic medical record. Descriptive statistics were used to calculate the rate of postnatal palliative consult and infant mortality rates.
Results: 181 mother-infant dyads were identified as having a PPC consultation and had available data following birth. Overall perinatal mortality was 65%; 51% of all liveborn infants died prior to discharge. Only 48.1 % of liveborn infants who lived for more than 24 hours received postnatal palliative care. Location of birth (primary versus non-network hospital) was significantly associated with postnatal PPC consult rate (p=0.007).
Conclusion: Continuation of palliative care after birth in families who received perinatal palliative care is inconsistently achieved. Creating reliable systems for PPC continuity will depend on location of care.
The Relationship Between Oxidative Stress and Hematological Parameters in Ghanaian Patients With Chronic Kidney Disease
Authors: Asmah Richard Harry , Archampong Timothy , Amoakohene Francis Newton , Amegatcher Gloria , Attoh Seth , Adedia David , Botchway Felix , Doku Derek , Squire Daniel
Published: January 2023

Background
Chronic kidney disease (CKD) is a major cause of morbidity and mortality worldwide with a rising burden in sub-Saharan Africa. Evidence from previous studies suggest high oxidative stress levels in CKD patients. Anti-oxidative enzymes such as superoxide dismutase (SOD) are impaired in kidney disease. Oxidative stress situations result in red blood cell dysfunction, platelet destruction and tissue injury. In this study we investigated hematological indices and superoxide dismutase activity during CKD.
Methods
The study utilized a cross-sectional design consecutively recruiting patients attending the Renal Unit of Korle-Bu Teaching Hospital (KBTH), Accra, with known CKD (n = 41). Healthy subjects (n = 41) from the Outpatients Department (KBTH) were recruited as controls. Blood samples were collected to determine hematological indices. The oxidative stress level in cases and control groups were determined by measuring superoxide dismutase enzyme activity. A diagnostic predictability analysis was also performed for the various parameters measured in this work.
Results
SOD activity level was significantly lower in CKD patients than in the control group (p < 0.0001). Red blood cell (r = 0.299; p = 0.039) hemoglobin (r = 0.383; p = 0.001) and hematocrit (r = 0.306; p = 0.005) correlated positively with SOD activity in cases compared with control group. Patients with CKD had significantly higher numbers of white blood cells (p < 0.0001), neutrophils (p < 0.0001) and lymphocytes (p = 0.0001) comparing with controls. White blood cell (WBC) (r= -0.331; p = 0.002), platelet levels (r= -0.234; p = 0.034) and neutrophil level (r= -0.238; p = 0.031) correlated negatively with SOD activity. In predicting CKD, SOD activity had sensitivity of 66% and specificity of 100% while WBC had higher sensitivity of 76% and comparable specificity of 90%.
Conclusion
SOD activity correlated negatively with total white blood cell, neutrophils and platelets. Red blood cells, hemoglobin concentration, and hematocrit indices had positive correlation with SOD activity. Both SOD and WBC had high specificity, 100% and 90%, respectively for the occurrence of CKD. In predicting CKD, WBC had a relatively higher sensitivity to SOD and could play a role in risk stratifying patients in resource-limited settings.
Machine learning for predicting the risk stratification of 1-5 cm gastric gastrointestinal stromal tumors based on CT
Authors: Zhang Cui , Wang Jian , Yang Yang , Dai Bailing , Xu Zhihua , Zhu Fangmei , Yu Huajun
Published: January 2023

Backgroud: To predict the malignancy of 1-5 cm gastric gastrointestinal stromal tumors (GISTs) in a CT risk assessment by machine learning (ML) using three models - Logistic Regression (LR), Decision Tree (DT) and Gradient Boosting Decision Tree (GBDT).
Methods: 309 patients with gastric GISTs enrolled were divided into three cohorts for training (n=161), as well as internal validation (n=70) and external validation (n=78). Scikit-learn software was used to build three classifiers. Sensitivity, specificity, accuracy and area under the curve (AUC) were calculated to evaluate the performance of three models. The diagnostic difference between ML models and radiologists were compared in internal validation cohort. Important features were analyzed and compared in LR and GBDT.
Results: GBDT achieved the largest AUC values (0.981 and 0.815) among three classifiers in training and internal validation cohorts and greatest accuracy (0.923, 0.833 and 0.844) in three cohorts. LR was found to have the largest AUC value (0.910) in external validation cohort. DT yielded the worst accuracy (0.790 and 0.727) and AUC (0.803 and 0.700) both in two validation cohorts. GBDT and LR showed more favorable performances than two radiologists. Long diameter was demonstrated to be the same and most important CT feature for GBDT and LR.
Conclusions: ML classifiers were considered to be promising in prediction of risk classification of gastric GISTs less than 5 cm based on CT, especially GBDT and LR due to the high accuracy and strong robustness. Long diameter was found as the most important feature for risk stratification.
Binary mixtures solids with nonlinear localized damping: General decay
Authors: Santos Mauro de L
Published: January 2023

We analyze the uniform general decay of the solution of a system modeling a mixture of two interacting continua with nonlinear localized damping acting in a arbitrary small region of the interval under consideration, assuming appropriate assumptions on the nonlinear terms. To do this, we used a observability inequality obtained for the conservative system combined with the Holmgren's uniqueness theorem and the reduction principle (see \cite{Daloutli}) where the problem of decay rates with nonlinear damping is reduced to an appropriate stabilizability inequality for the linear equation. This study generalizes and improves previous literature outcomes.
Biophysical Sequence Analysis of Functional Differences of Piezo1 and Piezo2
Authors: Phillips James
Published: January 2023

Because of their large size and widespread mechanosensitive interactions the only recently discovered titled transmembrane proteins have attracted much attention. Here we present and discuss their hydropathic profiles using a new method of sequence analysis. We find large-scale similarities and differences not obtainable by conventional sequence or structural studies. These differences support the evolution-towards-criticality conjecture popular among physicists. In this case the elastic properties are critical.
Effects of Natural Dietary Supplementation on Growth and Survival rate of Freshwater Ornamental Fish, Pseudotropheus demasoni (Konings, 1994)
Authors: Veeruraj Anguchamy , Ghosh Swagat , Mondal Arijit , Biswas Sumana , Ethiraj Kannapiran
Published: January 2023

Ornamental Fishery is one of the fast growing fisheries sector, for its increasing demands in world markets due to their attractive colour. Colouration is one of the essential supremacy qualities of the fish for consumer acceptability. Carotenoids are accountable for colouration of muscle in food fish and skin colour in ornamental fish. The present experiment was carried out to investigate the effect of three different natural feed supplements for the growth and survival rate in Demasoni Cichlids (Pseudotropheus demasoni). Totally 100 numbers of Demasoni Cichlids are equally distributed (10 fish in each tank) in ten different aquarium tanks and every 3 groups of cultural tanks were fixed with three different concentration of feed composition with remaining one fish tank as a control group. Four different treatments were selected for this present experiment with naturally obtained feed used as the base additive feed. Three different natural feed sources of raw materials tested were Dragon Fruit (Hylocereus undatus (Haw.), China Rose (Hibiscus rosasinensis L.) and Beetroot (Beta vulgaris L.), with an incorporation level of 7.5%, 10% and 12.5% respectively, including control feed without any natural feed additives. The total experiment was performed for a period of 60 days and all the fishes of each tank were fed with different feeds thrice a day. The preset study revealed that 12.5% of maximum value of crude protein was found in natural sources of dragon fruit could be incorporated in fish feed and it was expressed highest level of length and weight with 100% survival rates were found in each experimental tanks. The water quality parameters of all the experimental tanks were kept within the optimum range. The present result concluded that supplementation of incorporated Dragon Fruit, Beetroot and China Rose fish feed additives can successfully improve the growth and survival performance.
An Improved Parallel Feature Fusion - CBAM method for occluded pedestrian identification
Authors: Shaamili R. , Bevi A. Ruhan
Published: January 2023

Occluded pedestrian identification is a critical and challenging issue in the field of pedestrian detection. Currently, using pedestrian components or human approaches is the most popular way to get over the problem of occlusion in pedestrian recognition. Only a small portion of the body may be used for detection when there is severe occlusion from crowds, or human or pedestrian components. The viewable portions of the occluded pedestrian have a small scale, but the scales of the unobscured and occluded pedestrians in the same image are different. Improved Parallel Feature Fusion with CBAM (IPFF-CBAM) on Feature Pyramid Network is put forward that can integrate new feature data of various sizes which are applied to four benchmark datasets KITTI, WiderPerson, CrowdHuman, and INRIA individuals of occluded pedestrians, in order to enhance key attributes. According to the findings the proposed method performs satisfactorily on deep learning approaches i.e., Faster RCNN, Cascade RCNN and Mask RCNN to obtain results of parameters like Average Precision (AP) and Miss rate index (MR) in obstructed pedestrian detection tasks.
Applying an ICD-10-CA to ICD-11 Mapping Tool to Identify Causes of Death Codes in an Alberta Dataset
Authors: Doktorchik Chelsea , Southern Danielle A , King James A , Quan Hude
Published: January 2023

Background
The most recent and 11th revision of the International Classification of Disease (ICD-11) is in use as of January 2022, and countries around the globe are now preparing for the implementation of ICD-11 and transition from the 10th revision (ICD-10). Translation of current coding is required for historical comparisons.
Methods
We applied the World Health Organization (WHO) mapping tables to current Centers for Disease Control and Prevention (CDC) Lists of ICD-10 coding of causes of death to assess what ICD-11 codes look like in an Alberta sample of causes of death (COD). We prepared frequency tables for a single year of causes of death in Alberta based on the CDC grouping of COD.
Results
The mapping success rate for the adult population was 96.6% for unique ICD-10 COD codes and 99.5% for deaths. The mapping success rate was 100% for children and infants for both ICD-10 COD codes and deaths. We mapped ICD-11 codes to identify the ten most frequently reported COD in Alberta for 24,645 deaths in adults, children, and infants in 2017.
Conclusions
Apart from two codes, all ICD-10 codes could be mapped to ICD-11 for COD. These findings suggest that the ability to translate from the two iterations of coding will be feasible for future applications of health services data.
Derivation and validation of a nomogram model for venous thromboembolism in patients undergoing borderline resectable pancreatic cancer surgery
Authors: Cui Songping , Chen Qing , Lyu Shaocheng , Wang Jing , Wang Di , Li Binglin , He Qiang , Lang Ren
Published: January 2023

Background: Venous thromboembolism (VTE) is a common postoperative complication in patients with borderline resectable pancreatic cancer (BRPC), which seriously affects the quality of life and prognosis. We aimed to establish new nomogram to predict the VTE risk after BRPC surgery.
Method: A total of 301 consecutive adult patients who underwent BRPC surgery between Jan. 2011 and Dec. 2021 in our institution were retrospectively reviewed. Included in the cohort were 67 patients who developed VTE and 79 non-VTE patients. The patients were randomly divided into a training set and a validation set at a ratio of 7:3. A nomogram model was developed based on the results of univariate and multivariate logistic regression analysis in the training group. The predictive power of the nomogram was evaluated by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).
Results: The incidence of VTE in the present study was 45.9%. Age, albumin, operation time, tumor diameter and preoperative D-dimer were independent related factors. The areas under the ROC curve of the nomogram were 0.843 (95% CI: 0.782-0.904) and 0.893 (95% CI: 0.834-0.953) in the training and validation groups, respectively. For clinical usefulness, the model offered a net benefit in decision curve analysis, suggesting the new nomogram predict VTE events accurately enough.
Conclusion: We first established a high-performance nomogram of VTE risk in patients undergoing BRPC surgery, which helps clinicians to screen out people at high risk of VTE and perform prophylactic anticoagulation.
A novel UV-shielding reagent synthesized and its effects on properties of PVC
Authors: Wang Bin , Jiang Fan , Ma Xiangmei , Dong Zhehao
Published: January 2023

Poly(vinyl chloride) (PVC) is one of the most used polymers, but the mechanical and esthetic properties can deteriorate for use outdoors because of ultraviolet (UV) light or heat. The addition of stabilizers is indispensable method for improving the stability of PVC. In this work, a facile synthetic method of CeO2 quantum dots (QDs) was used, for achieving the best dispersion and improvement of anti-UV properties, the surface of CeO2 QDs was modified by ethyl 3,4-dihydroxybenzoate (EDHB), which was dispersed within the PVC matrix using the casting method to investigate the anti-UV and thermal properties. X-ray powder diffraction spectra (XRD), Infrared spectroscopy (FT-IR), High resolution transmission electron microscopy (HRTEM), UV spectrophotometr and thermogravimetric analysis (TGA) were applied to characterized the structures, morphologies and properties. The results highlighted that EDHB/CeO2 can help reduce damages of PVC upon exposure to ultraviolet (UV) light and heat.
Implementation of Fuzzy Mamdani Method to Classify Public Health Level in North Sumatra Province
Authors: Sihombing Sagita Charolina , Dahlia Agus
Published: January 2023

Health is one of the most important fields aspects in people’s lives. Public health is influenced by several factors, such as environmental factors and lifestyle. Every year, the government makes a program to improve people’s health and welfare. Therefore, the government needs to obtain information about the classification of public health levels to monitor the progress of the programs that have been carried out. The research created an interface application to classify the level of public health in North Sumatra Province. The research classified the public health level using data from Badan Pusat Statistik (BPS) in 2018. Next, the application was made using the Matlab 2013b GUI. Classification of the level of public health was carried out using the Fuzzy Mamdani method that generated public health classification levels based on the inputted indicators. Then, the level of health classification was divided into four parts: low, lower middle, upper middle, and high. The result shows that for the 2018 data, some cities/ districts are still at low health levels. However, many cities or districts have good health levels. The final result can be used as a reference for the government to analyze which cities/districts should be paid attention to improve their health and welfare.
Water infiltration rate in the Kathmandu Valley of Nepal amidst present urbanization and land-use change
Authors: Shrestha Ganga , Shakya Bijay Man , Shrestha Mohan Bikram , Khadka Udhab Raj
Published: January 2023

The rapid urbanization and land-use change prominently decreased groundwater recharge areas. Infiltration occurring through permeable areas is responsible for groundwater recharge. However, detailed studies of infiltration in low-income countries especially in human-encroached recharge areas are limited. Thus, this study mainly aims to measure the infiltration rate in the major recharge areas of the Kathmandu Valley (KV) using a double-ring infiltrometer (concentric ring size 30 and 15 cm). It also aims to estimate the volume of groundwater recharge with respect to the decrease in permeable areas in the northern part of the KV. The results revealed the infiltration rate ranging from 0.01 to 37.2 cm/h with an average of 7.3 ± 8.4 cm/h. The infiltration is found to be dependent upon land-use among different categories and organic matter among different soil properties. Additionally, the volume of water recharge in 2010, 2020, and 2030 was estimated as 67.73, 59.05, and 51.5 million cubic meters per year (MCM/year), respectively, which clearly showed a decrease in water recharge with respect to a decrease in the permeable areas. Hence, the findings would be useful for policymakers, stakeholders, and urban planners regarding the preservation and conservation of permeable areas for sustainable water resource management and urban flood management.
DESARROLLO DEL MEJORAMIENTO GENETICO EN CUYES EN EL PERU: Formación de nuevas razas
Authors: Chauca Francia Lilia
Published: January 2023

El desarrollo del mejoramiento genético de cuyes en el Perú se puede definir en tres etapas. La primera etapa (1965- 1970) tenía como objetivo conocer las características de la especie, mediante la evaluación de ecotipos nativos y la determinación de sus parámetros productivos y comportamiento. La segunda etapa (1970-2005) tenía como objetivo el proceso de selección por parámetros productivos. En el proceso de selección se consideraban características productivas con implicancia económica (precocidad y prolificidad). Fijadas estas características después de 30 generaciones de selección, fueron seleccionadas uniformizando su fenotipo predominante para buscar la distinguibilidad dentro de razas. La progenie registrada en cada raza tuvo una validación interna dentro de las estaciones del INIA así como en la academia. Concluido este proceso se entrega a productores para su validación y multiplicación. Analizando la información generada se aprueban los expedientes técnicos, se emiten las resoluciones oficiales y se procede a la liberación de las tres razas. La raza Perú (2004) es una base genética pesada usada en cruces terminales para ganar precocidad, alcanzando su peso de comercialización a las 8 semanas con un rendimiento de carcasa de 73% y conversión alimenticia de 3.01. La raza Andina (2005) fue seleccionada por prolificidad, con una fertilidad del 98.5% y un tamaño de camada de 3.4. La raza Inti (2013) fue seleccionada por peso y prolificidad, con un tamaño de camada de 3.2, peso a las 8 semanas de 900 g y rendimiento de carcasa de 71.1%. La tercera etapa (2005-2021) inicia con los cruzamientos interraciales, utilizando como base genética paterna a la raza Perú y como materna al cruce de Inti x Andina hasta llegar a los 5/8 Perú, la cual fue liberada como raza Kuri (2021). Estos cruzamientos buscan el mejor atributo de cada raza para lograr un individuo comercial que beneficie a los productores. La raza Kuri supera en tamaño de camada en 13.5% a la raza Perú, y en peso supera en 20% y 14% a las razas Andina e Inti respectivamente.
A Retrospective Single Centre Analysis of the Incidence of Hospital Admission
for Acute Coronary Syndrome During the COVID-19 Pandemic
Authors: Shah Nadim , Jamil Naser J.S. , Abdalla Geili , Muhammed Khalifa O , Al Hashimi Haitham A.R. , Baslaib Fahad O.
Published: January 2023

Background:

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic due to ‘coronavirus disease 2019’ (COVID-19) that has led to millions of deaths. This may have resulted in a change in the rate of admissions for other potentially life-threatening conditions such as acute coronary syndromes (ACS). Therefore, we investigated the incidence of ACS admissions during the current pandemic and compared it to a similar period the year before.

Methods:

This was a retrospective analysis of all patients admitted to a tertiary cardiology centre with ACS between February 2019 and the end of April 2019 (pre-COVID) that was compared with admissions between the same three months in 2020 (post-COVID). The main outcomes of interest were to evaluate any potential reduction of ACS admissions during the pandemic or change in mortality. In addition, we evaluated the rate of patients proceeding to coronary angiography (CAG).

Results:

During the post-COVID period, only 200 patients were admitted with ACS as compared to 331 patients during the pre-COVID period (39.6% reduction; 95% confidence interval (CI): 34% - 44%; p<0.01). A reduction in the percentage of patients proceeding to CAG was also noted (253 patients during the pre-COVID period compared to only 134 patients in the post-COVID period (76.4% vs 67.0%; p = 0.02)) but no associated reduction of primary percutaneous coronary intervention was noted. No increase in in-hospital mortality was noted between the pre-COVID and post-COVID groups (1.5% vs 1% respectively; p = 0.62).

Conclusion:

There was a significant reduction in admissions for ACS in the post-COVID period compared to a similar period prior. There was also a reduction in the overall invasive management of ACS, with less CAG performed but no associated reduction in the rate of PPCI. The in-hospital mortality rate was similar in the two groups.
Aldehyde Dehydrogenase-Mediated Cellular Relative Insensitivity to the Oxazaphosphorines1
Authors: Sladek Norman E.
Published: January 2023

As judged by findings in preclinical models, determinants of cellular sensitivity to cyclophosphamide and other oxazaphosphorines include two cytosolic aldehyde dehydrogenases, viz., ALDHlAl and ALDH3Al. Each catalyzes the detoxification of the oxazaphosphorines; thus, cellular sensitivity to these agenh decreases as cellular levels of ALDHlAl and/or ALDH3Al increase. Of particular
clinical relevance may be that stable sublines, relatively insensitive to the oxazaphusphorines Jue to elevated ALDHlAl or ALDH3Al levels, emerged when cultured human tumor cells were exposed only once to a high concentration of one of these agents for 30 to 60 minutes. Whether differences in cellular levels of either enzyme accounts for the clinically-encountered uneven therapeutic effectiveness of the oxazaphosphorines remains to be determined. However, it has already been established that measurable levels of these enzymes are found in some, but not all, tumor types, and that in those tumor types where measurable levels are present, e.g., infiltrating ductal carcinomas of the breast, they vary widely from patient to patient. Potentially useful clinical strategies that might be pursued if it turns out that ALDHIAl and/or ALDH3Al are, indeed, clinically operative determinants of cellular sensitivity to the oxazaphosphorines include 1) individualizing cancer chemotherapeutic regimens based, at least in part, on the levels of these enzymes in the malignancy of interest, and 2) sensitizing tumor cells that express relatively large amounts of ALDHlAl and/or ALDH3A 1 to the oxazaphosphorines by preventing the synthesis of these enzymes, e.g., with antisense RNA, or by introducing an agent that directly inhibits the catalytic action of the operative enzyme. Further, the fact that ALDHlAl and ALDH3Al are determinants of cellular sensitivity to the oxazaphosphorines provides the rationale for the investigation of two additional strategies with clinical potential, viz., decreasing the sensitivity of vulnerable and essential normal cells, e.g., pluripotent hematopoietic cells, to the oxazaphosphorines by selectively transferring into them the genetic information that encodes 1) ALDHlAl or ALDH3Al, or 2) a signaling factor, the presence of which would directly or indirectly, stably upregulate the expression of these enzymes.
Current Aspects of Antiandrogen Therapy in Women
Authors: Diamanti-Kandarakis Evanthia
Published: January 2023

Androgenic manifestations in appearance cause not only social and psychological distress for many women, but serious skin, reproductive and metabolic abnormalities as well. Antiandrogen therapy is one of the most promising therapies to treat androgenic disorders. Clinical studies with a variety of agents, including spironolactone, cyproterone acetate, flutamide and finasteride have now proven their utility in the treatment of hirsutism, acne, androgenic alopecia and ovulatory dysfuntion in hyperandrogenic women. Comparative clinical studies, especially with low-dose regimens, suggest that these agents are well tolerated and have the potential for broader clinical utility.
Brain Inflammation in Alzheimer Disease and the Therapeutic Implications
Authors: McGeer Edith G. , McGeer Patrick L.
Published: January 2023

Immunohistochemical studies suggested the existence of a chronic inflammatory condition in affected regions of the brain in Alzheimer disease (AD). Since inflammation can be damaging to host tissue, it was hypothesized that antiinflammatory drugs might inhibit both the onset and the progression of AD. This hypothesis is supported by a number of epidemiological studies suggesting that the prevalence of AD in persons is reduced by 40 - 50% in persons using antiinflammatory drugs. In one small pilot trial in early AD, the nonsteroidal antiinflammatory drug indomethacin appeared to halt the progressive memory loss. Immunohistochemical and molecular biological studies on immune system components in AD brain are revealing the complexities of the innate immune reaction. This very complexity may offer points of therapeutic intervention for new types of antiinflammatory agents. The complement system, microglia and cytokines are key components. This review summarizes the present state of knowledge on the immune system elements found in AD brain.
Solid-phase and Combinatorial Synthesis in β-Lactam Chemistry
Authors: Mata Ernesto G.
Published: January 2023

Combinatorial chemistry has became a core technology for the rapid development of novel lead compounds in the phannaceutical industry and for the optimization of therapeutic efficacy. The effort to prepare libraries of compounds by combinatorial chemistry has led to an unprecedented growth in solid phase organic synthesis (SPOS), particularly for the preparation of non-oligomeric small molecules
clinically valuable β-lactam compounds are very attractive targets for research using these new tecnmques. In recent years, β-lactam compounds have been recognized not only as unique antibacterial agents but also as potent enzyme inhibitors, drug delivery agents, and versatile synthetic intermediates. This review gives a comprehensive up-date for the application of solid-phase and combinatorial synthesis to β-lactam compounds.
Recent Advances in the Chemistry of β-Lactam Compounds as Selected Active-site Serine β-Lactamase Inhibitors
Authors: Mascaretti Oreste A. , Danelon Gerardo O. , Setti Eduardo L. , Laborde Marfa , Mata Ernesto G.
Published: January 2023

The β-lactamases catalyze the hydrolysis of the β-lactam bond of a variety of β-lactam antibiotics destroying their antibacterial activity. During the last decades, there has been an inexorable spread of β-lactamase genes into species that previously were not known to possess them.
One approach to combat the action of the β--lactamase is to inhibit the enzyme. However, inhibition of β- lactamase alone is not sufficient. The ability to penetrate the external membrane of Gram-negative bacteria, chemical stability, pharmacokinetics and other factors are also important in determining whether an inhibitor is suitable or not for therapeutic use.

This review takes recent examples of synthetic β-lactam compounds developed as active-site serine β-lactamase inhibitors, emphasizing information on their structures and their activity against Ambler classes A, C and D β-lactamases. In addition, examples based on rational design by computerized molecular modeling of crystal structure of the native enzyme and mechanism of the enzyme action are highlighted.
Approaches to the Prevention of Coronary Vascular Dysfunction Caused by Myocardial Ischaemia and Reperfusion
Authors: Woodman Owen L
Published: January 2023

The endothelium is an important regulator of coronary vascular tone due to its ability to release potent vasoactive substances such as the vasodilators nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF), prostacyclin (PGl2) and the potent vasoconstrictor endothelin. Endothelial dysfunction has been associated with a number of pathological states such as atherosclerosis, hypertension, diabetes and congestive heart failure. A disturbance of endothelial function may also contribute to the adverse effects that ischaemia and reperfusion exerts on the coronary vasculature. After ischaemia and reperfusion there is usually a selective impairment of endothelium-dependent relaxation in isolated coronary arteries. However, in the intact coronary circulation, there is a general loss of vasodilator reserve as responses to both endothelium-dependent and endothelium-independent agonists are attenuated. The release of vasoconstrictor(s) and plugging of capillaries with leukocytes may contribute to that impairment of the capacity of the coronary circulation to dilate together with the reduction in basal blood flow (no-reflow phenomenon). Ischaemic preconditioning is able to prevent ischaemic damage to the myocardium but the vasculature is less well protected as reperfusion is enhanced but the vasodilator reserve continues to be limited. Pharmacological preservation of vascular function has proved more successful with inhibitors of leukocyte adhesion, calcium channel blockers, endothelin receptor antagonists and inhibitors of oxygen radical generation all offering protection. Further refinement of protocols to preserve endothelial and vascular function after ischaemia will aid reperfusion, enhance vasodilator reserve and maximise recovery of myocardial function.
Circular RNAs: Insights into Clinical and Therapeutic Approaches for
Various Cancers
Authors: Akram Fatima , Haq Ikram ul , Nasir Narmeen , Shah Fatima Iftikhar
Published: January 2023

Background:

With the advent of cancer diagnostics and therapeutics, circular RNAs (circRNAs) are swiftly becoming one of the significant regulators of gene expression and cellular functions. A plethora of multiple molecular mechanisms has been observed to elicit their influence.

Objective:

Circular RNAs (circRNAs) are a distinct category of endogenous noncoding RNAs designed as a result of exon back splicing events in precursor’s mRNAs (pre-mRNAs) and are widely distributed in the transcriptome of eukaryotic cells.

Methods:

Although the role of circRNAs is still in its infancy, they serve as microRNA sponges, protein scaffolds, and modulators of transcription and splicing and occasionally as templates for the production of peptides.

Results:

It is well known that abnormal circRNA expression is prevalent in malignancies and has been linked to a number of pathophysiological aspects of cancer. This extensively anomalous expression assists in cellular proliferation and growth, sustaining cellular invasiveness and bypassing cellular senescence and death, thus advocating their promise to serve as both clinical biomarkers and therapeutic targets.

Conclusion:

An overview of the recent status of circRNA will aid in the identification of new biomarkers, therapeutic targets, and their prospect in the diagnosis and therapy of disease. In this review article, we discuss the functional mechanisms of circRNAs, their biomarker potential in disease diagnosis and prognosis, therapeutic approaches, and the associated limitations.
The Application of Pyrrolo[2, 3-d]pyrimidine Scaffold in Medicinal Chemistry
from 2017 to 2021
Authors: Liang Ting , Yang Yingxiang , Wang Jiayun , Xie Zhao , Chen Xin
Published: January 2023

The application of privileged structures in drug design is an effective strategy, which
usually leads to innovative hits/leads and successful structural optimization. Pyrrolo[2, 3-
d]pyrimidine are such a scaffold which are frequently used in many clinical drugs. The biocompounds
bearing pyrrolo[2, 3-d]pyrimidine skeleton show different pharmacological effects such as
anti-neurodegenerative, anti-inflammatory, antibacterial, and antitumor activities. In this article, we
reviewed the representative structures and biological characteristics of reported synthetic pyrrolo[2,
3-d]pyrimidine compounds from 2017 to 2021. The linked diseases and targets were also mentioned
briefly. This work might provide a reference for the subsequent drug discovery based on pyrrolo[2,
3-d]pyrimidine scaffold.
Agent in Urgent Need of Clinical Practice: Corilagin
Authors: Wang XueJia , Fisher David , Pronyuk Khrystyna , Dang Yiping , Zhao Lei
Published: January 2023

Corilagin is a naturally occurring water-soluble retrogallic acid tannin, which can be extracted
from many kinds of plants. Known at present, it is the main effective ingredient of Phyllanthus
urinaria L., Geranium wilfordii Maxim., Phyllanthus matsumurae Hayata, and Trifolium repens L. It
also exists in Phyllanthus emblica L., Dimocarpus longan Lour., Canarium album (Lour.) Raeusch.,
and Terminalia chebula Retz. It can participate in a variety of signaling pathways in vivo and has multiple
biological activities, including antitumor, anti-microbial, anti-oxidation, anti-inflammation, hepatoprotective,
anti-allergy, anti-proliferation and so on. Given the limited efficacy of first-line treatments
for many diseases such as oncology, chronic liver disease, and rheumatic immune system diseases,
and the potential for adverse effects to outweigh the therapeutic effects, attention is being focused
on alternative treatments, and natural plant extracts are a natural target for alternative treatments,
as natural substances tend to have low toxicity to normal tissues. Some proprietary Chinese
medicines containing corilagin have been used in clinical applications, being clinically applied to treat
chronic liver disease, viral hepatitis B, rheumatoid arthritis and other diseases. This paper reviews the
extraction, determination, distribution and harvesting, pharmacokinetics, biological activity, safety
assessment of corilagin and its application in clinical practice.
Identification and Evaluation of Nursing Errors in Kowsar Hospital by SHERPA
Authors: Motie Mahdieh , Rafiei Sima , Amiresmaili Mohammadreza , Amini Behnam , Aghdash Saber Azami , Kalavani Khalil
Published: January 2023

Background:

Medical errors, including human errors, are one of the most important and sensitive issues in the health system. Human errors can endanger patients’ life during health service provision. Therefore, healthcare workers should ensure the safety by reducing human errors. This study aimed to identify and evaluate human errors among nurses working at an Iranian Hospital.

Methods:

This is a cross-sectional study which was carried out using SHERPA method in 2018. After explaining the purpose of the study, data were collected by observation and interview. Using the hierarchical analysis method, tasks and subtasks were determined, and finally, the worksheet on SHERPA was completed and analyzed.

Results and Discussion:

Thirty-two tasks covering 252 subtasks related to the nursing profession were investigated, of which 252 errors were detected. Identified errors included errors of action, revision, retrieval, communication, and selection which were responsible for 60, 23, 3, 12, and 2 percent of errors, respectively. In terms of the level of error risk, 16 were unacceptable, 96 were undesirable, 107 were acceptable, which need revision, and 33 were acceptable with no need for revision.

Conclusion:

Nurses' errors are more action errors because of the nature of their work, so hospital authorities for safety and prevention should prioritize these errors.
Evaluation of the Quality of Clinical Education and the Clinical Self-efficacy of Nursing Students during the COVID-19 Pandemic
Authors: Khari Sorour , Pazokian Marzieh , Abadi Atefe Salimi Akin , Zarmehrparirouy Mina , NakhostinMoghadam Amirmohamad
Published: January 2023

Background:

Clinical education is the most important part of the education of nursing, operating room, and anesthesia students. During the COVID-19 pandemic and the suspension of clinical training, these students became very concerned. Nursing schools also limited clinical education to create a balance between the educational needs and safety of students. Therefore, the present study aimed to investigate the effect of changing clinical education conditions during the COVID-19 pandemic on the quality of clinical education and the clinical self-efficacy of nursing, operating room, and anesthesia students in Tehran, Iran.

Methods:

This descriptive cross-sectional study was conducted in 2020 on 277 seventh and eighth-semester nursing, operating room, and anesthesia students in Tehran, Iran. Students were selected by simple random sampling using a random number table. The study tools included the demographic questionnaire, the clinical education quality questionnaire, and the clinical self-efficacy questionnaire, which were sent to the participants via WhatsApp and Telegram after confirming their validity and reliability.

Results and Discussion:

64.30% of students were female, and the mean age was 23.59±3.49. The mean of total scores for the quality of clinical education and clinical self-efficacy was equal to 57.38±12.43 and 104.88±23.01, respectively. 57% of students considered moderate the level of the quality of clinical education and 51.60% of them moderate the level of clinical self-efficacy. The total score for clinical self-efficacy had a significant correlation with the quality of clinical education (r=0.12, P-value=0.04).

Conclusion:

The use of new educational methods, planning the course based on the needs of learners and in accordance with the conditions, and increasing the capability and the clinical self-efficacy of nursing students should be considered by nursing professors.
Macroporous Nanostructured Calcium Phosphate/Chitosan-Gelatin
Composite Bone Tissue Engineering Scaffold
Authors: Nezafati Nader , Beman Efaf , Borhan Shokoufeh , Hesaraki Saeed
Published: January 2023

Background:

Tissue engineering is an emerging technology developed for the therapeutic
reconstruction of damaged tissue.

Objective:

In this study, a ceramic/polymer nanocomposite bone tissue engineering scaffold was
prepared by coating a tetracalcium phosphate/dicalcium phosphate mixture slurry on a porous 3D
chitosan-gelatin construction.

Methods:

The phase composition, structural groups, and morphological aspects of the samples
were characterized. Furthermore, the 3D composite scaffold was immersed in simulated body
fluid (SBF) solution at 37ºC for various periods to track its compositional and structural changes.

Results:

Based on the results, the coated layer is composed of needle-like carbonated apatite nanosized
crystals with some tetracalcium phosphate/dicalcium phosphate initial materials. The
nanocomposite was porous with an average macropore size of about 410 μm. The in vitro tests
revealed that the composition of the coated layer tends to be apatite crystals, which are similar to
natural bone in terms of chemistry and morphology.

Conclusion:

The results suggest that a simple coating of chitosan-gelatin scaffolds using reactive
calcium phosphate particles may introduce a novel nanocomposite scaffold with improved mechanical
strength, bioactivity, and osteoconductivity.
Hepatitis E virus and Zoonosis: Recent Advances and Therapeutic Implications
Authors: Hon Kam L.E. , Leung Alexander K.C. , Wong Alex H.C. , Sridhar Siddharth
Published: January 2023

Hepatitis E is viral hepatitis caused by infection with the hepatitis E virus (HEV). This
article aims to review HEV disease and recent advances in the management of hepatitis E. We
used PubMed Clinical Queries and keywords of “hepatitis E”, “hepatitis E virus” AND “zoonosis”
as the search engine. “Therapy”, “Clinical Prediction Guides”, “Diagnosis”, “Etiology” and
“Prognosis” were used as filters, and “Narrow” scope was used. The search was conducted in
April 2022. The information retrieved from the above search was used in the compilation of the
present article. Hepatitis E is viral hepatitis caused by infection with the hepatitis E virus (HEV).
Hepatitis E has mainly a fecal-oral transmission route. Hepatitis E infection usually follows an
acute and self-limiting course of illness with low death rates in resource-rich areas; however, it can
be more severe in pregnant women and immunocompromised people. The mortality rates in these
groups are substantially higher. A vaccine for HEV is available but is not universally approved.
Ribavirin remains the most efficacious medication for the treatment of HEV but is contraindicated
in pregnancy. Sofosbuvir and pegylated interferon, with or without ribavirin, have not been shown
in the latest literature reviews to provide reliable additional benefits to the treatment of hepatitis.
Sofosbuvir should not be used as monotherapy for HEV. Food is an important source of infection
in many countries while rats are the primary vector in developing nations. Management must include
an understanding of the rat habitats for this zoonotic disease. Hepatitis E remains an important
cause of hepatitis and a zoonotic disease globally. Public health policies are key to containing
this viral infectious disease, including policy in the transfusion of blood products.
Molecular Sub-Typing and Exploration of Key Signalling Pathways Involved in Complicating the Disease
Authors: Anto Nikhil Ponnoor , Muraleedharan Amitha , Mittal Rashmi
Published: January 2023

Triple-negative breast cancer is characterized by distinct molecular profiles,
unique metastatic patterns, aggressive behavior, lacks the targeted therapeutic
approach, and caused significant mortality worldwide. The molecular complexity of
angiogenesis, autophagy, apoptosis, and metastasis process in TNBC has fostered
research efforts to unleash the molecular, pathological, and genetic drivers of their
lethal cascade. This complex disease entity involves PI3k/Akt/mTOR, NF-kB, ERRs,
and miRNA trafficking which has further worsened the clinical outcome. Due to their
heterogeneous nature, none of the drugs were able to completely target the TNBC
tumor spectrum. This chapter highlights the classification of TNBC on the basis of
aberrated copy number, histology, proteomic, and mutational profiles to understand the
aetiology of the disease. The identification of therapeutic vulnerabilities was also
carried out by gaining insights into the above-mentioned signalling pathways and their
role in further complicating the disease. 