bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of tumor suppressor gene LHPP-based 5-microRNA signature that predicts the early and mid-stage esophageal squamous cell carcinoma: a two-stage case-control study in the Chinese Han population
Authors: Zhao Xiang , Zhu Xiaocun , Wang Luoshai , Chen Yurao , Chen Ronghuai , Zheng Zemao , Yang Hengjin , Xia Wan , Yao Juan , Zhao Kun
Published: April 2022

Global Cancer Statistics 2020 estimated that there were 544,076 deaths from esophageal cancer. It has been confirmed that phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is an important tumor suppressor gene in many solid tumor tissues, but its expression in esophageal squamous cell carcinoma (ESCC) has not been reported. Furthermore, this study explored LHPP-based microRNA (miRNA) signatures for predicting early and mid-stage ESCC. We used next-generation sequencing to analyze and screen out the miRNAs differentially expressed in ESCC tissues. Besides, we explored the expression profile of miRNAs involved in LHPP regulation through miRDB, TargetScan, and miRanda online prediction systems. A model for ESCC prediction was established based on a testing cohort of 75 ESCC patients and 75 healthy controls. Finally, the predictive model was evaluated using a validation cohort of 45 ESCC patients and 45 healthy controls. Compared with adjacent tissues, LHPP protein levels in early and mid-stage ESCC tumor tissues were significantly decreased (P<0.01). Next-generation sequencing and three biological online prediction systems indicated that miR-15b-5p, miR-424-5p, miR-497-5p, miR-363-5p, and miR-195-5p regulate LHPP expression. The levels of the above five miRNAs and squamous cell carcinoma antigen (SCC) in plasma were significantly increased in the early and mid-stage ESCC patients (P<0.05). Then, an ESCC prediction model combining these five miRNAs and SCC was established. Finally, in an external validation cohort, the model exhibited a high discriminative value (sensitivity/specificity: 84.4%/93.3%). The combined noninvasive model we constructed has potential implications for the noninvasive diagnosis of early and mid-stage ESCC.
Enhanced self-phase modulation in silicon nitride nanowires with integrated graphene oxide 2D films
Authors: Moss David
Published: April 2022

We experimentally demonstrate enhanced self-phase modulation (SPM) in silicon nitride (Si3N4) waveguides integrated with 2D graphene oxide (GO) films. GO films are integrated onto Si3N4 waveguides using a solution-based, transfer-free coating method that enables precise control of the film thickness. Detailed SPM measurements are carried out using both picosecond and femtosecond optical pulses. Owing to the high Kerr nonlinearity of GO, the hybrid waveguides show significantly improved spectral broadening compared to the uncoated waveguide, achieving a broadening factor of up to ~ 3.4 for a device with 2 layers of GO. By fitting the experimental results with theory, we obtain an improvement in the waveguide nonlinear parameter by a factor of up to 18.4 and a Kerr coefficient (n2) of GO that is about 5 orders of magnitude higher than Si3N4. Finally, we provide a theoretical analysis for the influence of GO film length, coating position, and its saturable absorption on the SPM performance. These results verify the effectiveness of on-chip integrating 2D GO films to enhance the nonlinear optical performance of Si3N4 devices.
Predisposing and Reinforcing Factors of Undernutrition Among 0-to 59-Months-Old Children in Rural Communities of Central Malawi
Authors: Chilanga Maureen , Chilanga Emmanuel
Published: April 2022

Background
Child undernutrition is a public health problem in Malawi. In 2015, about 23% of child mortality was linked to the phenomenon. Child undernutrition is more prevalent in rural areas and there is limited data to inform rural-specific programs. The aims of this study are to examine the prevalence and predisposing factors of undernutrition among 0–59 months-old children in rural central Malawi.
Methods
A cross-sectional study design was used. A total of 538 child/mother dyads were systematically selected from postnatal clinics. Anthropometric assessment techniques and socio-demographic questionnaire was used to collect data. Child Z-scores for anthropometric data were calculated using Anthro v3.2.2. Logistic regressions were used to determine correlates of undernutrition.
Results
The rates of stunting, underweight, and wasting were 42%, 11%, and 3%, respectively. In multivariable logistic regression models, limited access to safe water, and maternal exposure to intimate partner violence (IPV) were risk factors of child stunting (OR = 1.72, CI: 1.13–2.61) and (OR = 1.505, CI: 1.001–2.261) respectively. Child deworming, born at a low weight, and food insecurity were some of risk factors of child underweight (OR = 2.14, CI: 1.18–3.89), (OR = 2.41, CI: 1.23–4.71), and (OR = 1.89, CI: 1.01–3.51) respectively. Households that were near domestic water supply had low risk of registering wasted children (OR = 0.18, CI: 0.41–0.79).
Conclusions
Only the prevalence of child stunting is greater in central Malawi compared to national level. This study suggests that child nutrition planners in Dowa district should pay attention to water access, food security, child deworming, childbirth weight, and IPV.
Risk Factors of Depression Among Mothers of Children with Chronic Health Conditions and Disability in Central Malawi
Authors: Chilanga Emmanuel , Chilanga Maureen
Published: April 2022

The number of pediatric chronic health conditions and disabilities (PCHCD) in Malawi are rising. Caregivers of children with chronic health condition and disabilities (CHCD) experience elevated depression that undermine optimum childcare support. Currently, there is dearth of knowledge on the prevalence and underlying factors that predispose depression among mothers of children with CHCD in Malawi. The study aims to examine the perceived social environmental factors that triggers anxiety and depression among mothers of children with CHCD in rural Malawi. Methods The study utilized a sequential mixed-method research design. A multistage cross-sectional study design was used to sample 198 mothers for the survey, and purposively recruited 27 mothers for the in-depth interviews. A descriptive analysis examined the prevalence of depression. A phenomenological approach was used to understand the drivers of depression. The qualitative interviews were transcribed and subsequently coded using thematic analysis. Results The prevalence of depression among mothers of children under five years with CHCD was 47%. Notable perceived predisposing factors of depression were constant fear of their child’s well-being and safety, lack of community and professional support, and inaccessibility of specialized healthcare services due to poverty. Conclusion Depression among mothers of children with CHCD is a significant health problem in rural Malawi that warrant intervention. We suggest that programs that can enhance the wellbeing and safety of children and offer socioeconomic support to mothers can potentially mitigate depression.
Go Fund My Life: Challenging the Meritocracy Narrative of Online Medical Fundraisers
Authors: Lanius Candice , Fisk Nathan
Published: April 2022

Crowdfunding websites rely on a myth of equal access for all, but that claim has not been tested empirically. In this study, 5,440 medical crowdfunding campaigns were analyzed to identify trends in who gets funded. Initial findings show urban and wealthy fundraisers receive more funds, a pattern that we theorize relates to microcelebrity status. Racial differences were only partially found, with Native Americans receiving more social media shares and higher dollar amounts. A thematic and sentiment analysis of the campaigns found tropes and emotional tones that were consistent across the campaigns. Future analysis may reveal patterns related to rhetorical performance in the fundraisers request and how that relates to success.
Using machine learning to assess cardiovascular risk in T2DM patients without established cardiovascular disease: The MARK-2 analysis
Authors: GHOSAL SAMIT , Sinha Binayak
Published: April 2022

Background:Cardiovascular (CV) risk assessment is the cornerstone for choosing the most appropriate antihyperglycemic agent. One of the major obstacles in the use of such scores is that the process is time consuming, which is a deterrent in a busy clinic. The aim of the present analysis was to explore means of reducing the number of inputs to make the scoring faster and more acceptable to physicians.Methods:We used the MARK survey dataset to assess the utility of the QRISK 3 CV risk score in the Indian population (n=1,538); participants were recruited from five zones (east, west, north, south, and central). Machine learning techniques were used to analyze the existing MARK data. The XGBoost algorithm was used to create the model needed to identify the clinical parameters of interest. Dimension reduction techniques were employed to identify the clinical parameters of importance based on the accrued gain values. As the final step, a confusion matrix was created to assess the model’s accuracy and precision.Results:We identified ten parameters of clinical interest that could predict the 10-year CV risk and were comparable with the QRISK 3 score (with 21 parameters). The parameters identified by machine learning (ML) were age, sex, BMI, smoking status, blood pressure, treatment with antihypertensive agents, angina, total cholesterol, the total cholesterol/HDL ratio, and CKD. This dimension reduction was possible with a model accuracy of 95.12%.Conclusion:There were ten routinely assessed parameters identified with machine learning techniques that can assist physicians in determining the CV risk of T2D patients within a short period of time.
Identifying exposure pathways mediating adverse birth outcomes near active surface mines in Central Appalachia
Authors: Ruktanonchai Corrine Warren , McKnight Molly Xi , Buttling Lauren Grace , Kolivras Korine N , Krometis Leigh-Anne , Gohlke Julia M
Published: April 2022

Background: Previous work has determined an association between proximity to active surface mining within Central Appalachia and an increased risk of preterm birth (PTB) and low birthweight (LBW). Multiple potential exposure pathways may exist, however, including inhalation of particulate matter (airshed exposure), or exposure to impacted surface waters (watershed exposure). We hypothesize that this relationship is mediated by exposure to contaminants along one or both of these pathways. Methods: We geolocated 194,084 birth records through health departments in WV, KY, VA and TN between 1990 and 2015. We performed a mediation analysis, iteratively including within our models: a) the percent of active surface mining within 5 km of maternal residence during gestation; b) the cumulative surface mining airshed trajectories experienced during gestation, and; c) the percent of active surface mining occurring within the watershed of residency during gestation.Results: Our baseline models found that active surface mining was associated with an increased odds of PTB (1.09, 1.05 – 1.13) and LBW (1.06, 1.02 – 1.11), controlling for individual-level predictors. When mediators were added to the baseline model, the association between active mining and birth outcomes became non-significant (PTB: 0.48, 0.14 – 1.58; LBW 0.78, 0.19 – 3.00), while the association between PTB and LBW remained significant by airshed exposure (PTB: 1.14, 1.11 – 1.18; LBW: 1.06, 1.03 – 1.10).Conclusions: Our results found that surface mining airsheds at least partially explained the association between active mining and adverse birth outcomes, consistent with a hypothesis of mediation, while mediation via the watershed pathway was less evident.
The Mirror Reversal Mechanism on Black Hole Collapse and Singularity Eruption in Cosmic Continuum
Authors: Wang Xijia
Published: April 2022

In the Big Bang Theory and the Black Hole Theory, the existing laws of physics all fail at the singularity, and the singularity has become a blind spot in the existing scientific theories. In this paper, the mechanism of black hole collapse and singularity eruption are deduced using the axiom system of the cosmic continuum. The universe was not created by an instantaneous explosion, but by the continuous eruption of singularities. As long as the singularity is still erupting, the universe will not stop expanding. The cosmic system collapse into a Schwarzschild black hole under the action of a strong gravitational field, and the Planck spheres at the center of the black hole continues to collapse into dark mass bodies, forming dark celestial body and singularity. The Schwarzschild radius is the upper limit of a black hole, and the Planck sphere is the lower limit of a black hole. The singularity is the conversion point between the old and new cosmic systems. The singularity erupts the Planck spheres under the action of a strong gravitational field, and the Planck spheres expands outward to form a new cosmic system. The Planck sphere is both the end of the old cosmic system and the starting point of the new cosmic system. The black hole collapse and the singularity eruption are mirror images of each other. The Planck sphere is the front of the mirror, and the singularity is the back of the mirror.
Medical Waste Management Practices at Healthcare Facilities in Cape Coast Metropolis
Authors: Agyekum Nana Kusi , Wilson Ansah Edward
Published: April 2022

Objectives: This study examined the level of knowledge of health hazards associated with medical waste management, among healthcare workers and management staff of healthcare facilities in the Cape Coast Metropolis.
Methods: Three hundred and twenty (320) healthcare workers were surveyed from two public hospitals in the Metropolis and 7 management staff were purposefully selected and interviewed. The participants include nurses, orderlies, administrators, and environmental health officers. Frequency, percentages and linear regression analyses were performed on the data.
Results: The results showed that 95.9% (n = 307) of health professionals recorded good knowledge about management of medical waste in their facilities. However, arrangement for managing medical waste was inadequate at the facilities (Mean = 1.47, SD = 0.221, CV = 15.03%). The finding revealed that compliance with occupational health and safety guidelines was high (Mean=3.99, SD=0.39, CV=9.82%). Moreover, regression analysis indicated that training is a strong predictor of medical waste practices (0.357) even though educational level, working experiences, and age of the workers were also predictors (-0.356; -0.103; 0.010).
Conclusion: Level of knowledge of hospital workers on medical waste health hazards is high, but arrangements for managing such waste are inadequate or weak. Compliance to Ministry of Health’s occupational health and safety guidelines is high. Meanwhile, training of healthcare workers would increase their medical waste management practices. A well-structured training with appropriate storage facility and good supervision at the point of waste generation should be prioritized to assist workers to practice safer and proper waste segregation.
La recepción contemporánea del “Fragmento sobre las máquinas” de Marx: crítica y lineamientos para una reinterpretación
Authors: Pagura Nicolás Germinal
Published: April 2022

El llamado “Fragmento sobre las máquinas” de Marx se ha convertido en las últimas décadas en uno de sus textos más recuperados. Esto ha ocurrido, indudablemente, bajo el influjo de la lectura realizada por la corriente del autonomismo italiano, para la cual se trata de un texto que anticiparía la etapa del capitalismo que se abre tras la crisis de la década de los setenta. El “Fragmento” permitiría articular teóricamente esta etapa en términos de una “crisis de la medida del valor” que advendría por la imposibilidad de encuadrar en la norma del tiempo de trabajo socialmente necesario la nueva fisonomía que adquiere el trabajo en el “posfordismo”. El objetivo fundamental de este artículo es discutir esta clave interpretativa del “Fragmento” y articular conceptualmente sus elementos centrales a fin de emprender una relectura alternativa de éste, que también serviría para analizar críticamente el capitalismo actual.
“Razón y vida se llaman mutuamente”. Reflexiones sobre la imagen del organismo en Kant y en Hegel
Authors: Palermo Sandra
Published: April 2022

El trabajo intenta poner en evidencia las diferentes declinaciones del doble movimiento conceptual de la razón al organismo y del organismo a la razón que hallamos en Kant y en Hegel y las implicaciones de tales diferencias para sus respectivos sistemas filosóficos y para su concepción de la razón. Mientras que en Kant el movimiento de la razón al organismo y del organismo a la razón se declina de manera “interrumpida”, de suerte que el paso nunca se cumple acabadamente, Hegel, presentando el organismo como la “razón en forma sensible”, abre la posibilidad de una inteligibilidad completa de aquel, garantizándose al mismo tiempo el espacio conceptual para una acabada comprensión de sí de la razón en el sentido de lo viviente. Aún así, si el organismo viviente es instanciación de la razón, tal instanciación se presenta como inacabada, pues el animal es incompleta realización de aquella. En este sentido, la relación razón-organismo parece declinarse en un movimiento jerárquico en el que el segundo se subordina a la primera. Sin embargo, Hegel habla del movimiento de autoefectuación de sí de la razón como el movimiento en el que esta muestra su carácter orgánico y viviente.
Individuo y comunidad en el pensamiento mítico
Authors: Esparza Urzúa Gustavo Adolfo , Junco Ethel
Published: April 2022

En este artículo establecemos que en el pensamiento mítico existe, como cualidad natural, una expresión de universalidad. Siguiendo la Filosofía de las formas simbólicas de Cassirer, mostraremos que a través de la función expresiva del mito es posible desarrollar un pensamiento expresivo o un modo prelógico de conocer. Se propone después una interpretación de Edipo en Colono para mostrar que (i) esta obra ofrece un recurso plausible para relacionar al individuo y la comunidad, y que (ii) el entramado opera como un complejo camino sígnico y simbólico para delinear una forma de relación expresiva en donde es posible la unificación del individuo con la comunidad.
Reflexiones sobre la extinción del Yo
Authors: Ordóñez Roig Vicente
Published: April 2022

El pensamiento occidental supone que hay un Yo singular, unitario y sólido, valor supremo y cimiento o base de la libertad, el autoconocimiento y la autenticidad. Ahora bien, ¿hay realmente un Yo autoidéntico y unitario? ¿Es responsable el Yo del control de lo que ocurre en su interior? ¿O algo se le escapa? ¿Puede la autoexploración revelar elementos desconcertantes de su configuración interna? ¿Es posible anular y, en última instancia, extinguir el Yo? El objetivo de este artículo es proporcionar posibles respuestas a estas y otras cuestiones derivadas del análisis de algunas de las aportaciones más significativas de la filosofía occidental y la budista al estudio del Yo.
Valorization of spent coffee grounds through pyrolysis as adsorbent for the removal of Vivizole Red 3BS dye from aqueous solution
Authors: Adamu Admasu , Zewge Feleke , Chebude Yonas
Published: April 2022

Ever-increasing coffee consumption results in the generation of a significant amount of solid residue in the form of spent coffee grounds (SCG) and their subsequent disposal causes environmental pollution. Valorization of SCG through pyrolysis could be one of the solutions to this challenge. Pristine biochar of SCG shows less efficiency to remove dyes from aqueous solutions. Herein, iron(III) salt was used as a catalyst during the carbonization of SCG and has a good graphitization efficiency and thus enhanced the formation of aromatic structures, which provide adsorption sites for the dye. The physical characteristics of the prepared biochar were analyzed by FTIR, XRD, and BET. A predictive model for the removal of the dye was investigated with the Design Expert 11.0 software through the central composite design (CCD) - response surface methodology (RSM) by conducting a batch adsorption study, and the suggested optimum values of the CCD were 10 ppm initial dye concentration, 1 g per 100 ml adsorbent dose, and contact time of 101 min with optimum predicted dye removal of 99%. The Langmuir model was the best fitted isotherm model with an adsorption capacity of 2.07 mg/g, and the adsorption kinetic equilibrium data was better described by the pseudo-second-order model and from the thermodynamic study, it has been suggested that the adsorption process was spontaneous, favorable, endothermic, and a physicochemisorption in nature. The possible adsorption mechanisms governing the adsorption process of the dye with biochar are π – π electron donor-acceptor interactions and hydrogen bonding.
A hybrid artificial neural network: An optimization-based framework for smart groundwater governance
Authors: El Mezouari Asmae , El Fazziki Abdelaziz , Sadgal Mohammed
Published: April 2022

Given the growing scarcity and strong demand for water resources, the sustainability of water resource management requires an urgent policy of measures to ensure the rational use of these resources. The heterogeneous properties of groundwater systems are related to the dynamic temporal-spatial patterns that cause great difficulty in quantifying their complex processes, while good regional groundwater level forecasts are completely required for managing water resources to guarantee suitable support of water demands within any area. Water managers and farmers need intelligent groundwater and irrigation planning systems and effective mechanisms to benefit from the scientific and technological revolution, particularly the artificial intelligence engines, to enhance the water support in their water use planning practices. Therefore, this work aims to improve the groundwater level prediction based on the previous measures for better planning of hydraulic resource use. For this concern, the suggested method starts with data-preprocessing using the Principal Component Analysis method. Next, we validated the effectiveness of the hybrid artificial neural network, combined with an extended genetic algorithm for the hyperparameters and weight optimization, in predicting the groundwater levels in a selected monitoring well in California. The evaluation results have demonstrated the performance of the optimized ANN-GA model.
The Effect of Probiotic and Synbiotic Consumption on the Most Prevalent
Chemotherapy-related Complications: A Systematic Review of
Current Literature
Authors: Arab Arman , Karimi Elham , Bagherniya Mohammad , Sathyapalan Thozhukat , Sahebkar Amirhossein
Published: April 2022

Background:

To date, many investigations have employed pro-/synbiotic to examine
their effects on chemotherapy-related side effects; nevertheless, their findings are inconclusive.
To address this issue, we carried out a systematic review to explore the effect of pro-
/synbiotic consumption on chemotherapy-related side effects, including nausea, vomiting, mucositis,
diarrhea, and constipation in adults using randomized controlled trials (RCTs).

Methods:

The electronic databases, including PubMed, Scopus, and ISI Web of Sciences,
were searched systematically from the earliest available date to March 2021 to identify eligible
studies. The quality of the enrolled studies was assessed based on the Cochrane
Collaboration Risk of Bias tool.

Results:

A total of 10 studies involving 788 individuals were included in the current
systematic review, with the sample size ranging from 25 to 200 and the mean age ranging
from 51.04 to 66.91 years. The findings of this study imply that probiotic consumption
may be more effective in terms of mucositis compared to other complications.

Conclusion:

Further good-quality RCTs with better methodology are required to determine
whether and how pro-/synbiotics can prevent or treat chemotherapy-induced side effects.
The current systematic review findings may help investigators of future studies in
selecting the study population and probiotic strains.
Favipiravir in SARS-CoV-2 Infection: Is it Worth it?
Authors: Batiha Gaber El-Saber , Alexiou Athanasios , Moubarak Mohamed , Shaheen Hazem M. , Zakariya Ali M. , Usman Ibe M. , Rauf Abdur , Adhikari Achyut , Dey Abhijit , Hetta Helal F. , Al-Gareeb Ali I. , Al-kuraishy Hayder M.
Published: April 2022

Favipiravir is a potential antiviral drug undergoing clinical trials to manage various viral
infections, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Favipiravir
possesses antiviral properties against RNA viruses, including SARS-CoV-2. Unfortunately, these
viruses do not have authorized antiviral drugs for the management of diseases resulting from their
infection, hence the dire need to accentuate the discovery of antiviral drugs that are efficacious and
have a broad spectrum. Favipiravir acts primarily by blocking inward and outward movements of
the virus from cells. Favipiravir is a prodrug undergoing intracellular phosphorylation and ribosylation
to form an active form, favipiravir-RTP, which binds viral RNA-dependent RNA polymerase
(RdRp). Considering the novel mechanism of favipiravir action, especially in managing viral
infections, it is vital to pay more attention to the promised favipiravir hold in the management
of SARS-CoV-2, its efficacy, and dosage regimen, and interactions with other drugs.
In conclusion, favipiravir possesses antiviral properties against RNA viruses, including COVID-
19. Favipiravir is effective against SARS-CoV-2 infection through inhibition of RdRp. Pre-clinical
and large-scalp prospective studies are recommended for efficacy and long-term safety of favipiravir
in COVID-19.
A Review on Benzimidazole Scaffolds as Inhibitors of Mycobacterium
tuberculosis Mycolyl-arabinogalactan-peptidoglycan Complex Biosynthesis
Authors: Pappachen Leena K. , Bhaskar Vaishnav , Kumar Sunil , Nair Aathira S. , Rajappan Krishnendu P. , Sudevan Sachithra T. , Parambi Della G.T. , Al-Sehemi Abdullah G. , Zachariah Subin M.
Published: April 2022

Background:

Tuberculosis is one of the oldest known infectious diseases to mankind,
caused by Mycobacterium tuberculosis. Although current treatment using first-line anti-tubercular
drugs is proven to be effective, an infection caused by resistant strains, as in multidrug-resistant
and extensive drug- resistant tuberculosis is still an impending challenge to treat.

Objective:

Our objective is to focus on reporting benzimidazole derivatives that are targeting mycobacterial
membrane biosynthesis, particularly the mycobacterial mycolyl-arabinogalactanpeptidoglycan
complexes. From the literature survey, it has been noted that targeting Mycobacterium
tuberculosis cell membrane biosynthesis is an effective approach to fight against drug
resistance in tuberculosis.

Methods:

Articles on benzimidazole derivatives as inhibitors of proteins responsible for the biosynthesis
of the mycobacterial mycolyl-arabinogalactan-peptidoglycan complex have been selected.

Results:

By reviewing the anti-tubercular activity of the reported benzimidazole derivatives, we
have concluded that a correlation between benzimidazole derivatives and their biological activity is
found. It has been noted that benzimidazole derivatives with substitution at N1, C2, C5, and C6 positions
have shown a greater affinity towards target proteins.

Conclusion:

Even though scientific advancement toward the prevention of tuberculosis has been
quite significant in the past few decades, infection caused by resistant strains is a major concern.
We have collected data on benzimidazole derivatives that inhibit the biosynthesis of mycolic acid,
arabinogalactan and, peptidoglycan. From our observations, we conclude that majority of the molecules
have given anti-tubercular activity in nanomolar range. Still there are few mycobacterial
membrane biosynthesis proteins where benzimidazole as an inhibitor has yet to be explored.
Design and Metal-Free Synthesis and Cytotoxicity Evaluation of 5Hchromeno[ 4,3-b]pyridine Derivatives as Anti-Proliferative Agents
Authors: Rao M. Sayaji , Reddy Basi Venkata Subba , Kamireddy Kamalaker Reddy , Bantu Rajashaker , Misra Sunil , Sridhar Balasubramanian
Published: April 2022

Background:

A novel metal-free approach is reported for the synthesis of 5H-chromeno[4,3-b]pyridine derivatives. Indeed, chromene derivatives are found to exhibit a broad spectrum of biological activities such as antibacterial, antirhinovirus, antioxidant, cytotoxic, anticancer, and antimicrobial properties.

Methods:

This method provides an easy access to a large number of 5H-chromeno[4,3-b]pyridine scaffolds by the condensation of 3-formylchromene with -enaminoesters under thermal conditions. All compounds are well characterized by NMR, IR and mass spectrometry. This is a safe and convenient protocol.

Results:

Thus newly synthesized compounds are evaluated for their cytotoxicity against four human cancer cell lines, such as B16 (Skin cancer), DU145 (Prostate cancer), Hela (Cervical cancer) and CHO (Chinese hamster ovary).

Conclusion:

Among them, compounds 3n and 3o shows an excellent anti-proliferation activity against CHO (IC50 12.33+1.13 μM), Hela (IC50 22.33+0.51 μM), and B16 (IC50 27.61+0.8 μM) cell lines, while compounds 3c, 3g and 3q exhibits promising anti-proliferation against above four human cancer cell lines with IC50 14.96+1.9, 15.59+0.9, 13.8+0.06 μM, respectively, compared with a standard drug Doxorubicin & Mitomycin.
Optimization of Pharmacophore of Novel Hybrid Nucleus of 1,3,4-
oxadiazole-chalcone using Literature Findings and In silico Approach as
EGFR Inhibitor
Authors: Patil Shital M. , Bhandari Shashikant V.
Published: April 2022

Background:

Cancer is a leading cause of death worldwide. EGFR is one of the important
targets considered for current chemotherapeutic agents. The problem of drug resistance can be overcome
by the use of hybrid molecules. A hybrid of 1,3,4-oxadiazole and chalcone has been proved to be an anti-
EGFR inhibitor.

Objective:

The aim of the study was to carry out pharmacophore optimization of the hybrid nucleus of 1,3,4-
oxadiazole and chalcone by using literature findings and in-silico approach. A series of 24 substituted hybrid
molecules of 2-(5-phenyl-1,3,4-oxadiazol-2-ylthio)-N-(4-((Z)-3-phenylacryloyl)phenyl)acetamide derivatives
were subjected to 2D and 3D QSAR studies.

Method:

The survey of literature was carried out for selected hybrid nucleus using different available
databases. The 2D QSAR was performed by using the MLR, PLS, and PCR methods, while 3D QSAR
was performed using the KNN-MFA method.

Result:

A summary of literature findings was prepared. For 2D QSAR, statistically significant model was
obtained for the MLR method with r2=0.9128, q2=0.8065. For the 3D QSAR model, I was found to be significant
with q2=0.834. The pharmacophoric requirements for inhibition of EGFR were optimized by use of
the evidence attained after the generation of descriptors from QSAR studies and literature findings.

Conclusion:

This optimized pharmacophore will be useful in further drug design process.
Multi-Classification of Brain Tumors on Magnetic Resonance Images
Using an Ensemble of Pre-Trained Convolutional Neural Networks
Authors: Sen Gan , Wu Miao , Liu Qian , Yan Chuanbo
Published: April 2022

Background:

Automatic classification of brain tumors is an important issue in computer-aided diagnosis (CAD) for medical applications since it can efficiently improve the clinician’s diagnostic performance and current study focused on the CAD system of the brain tumors.

Methods:

Existing studies mainly focused on a single classifier either based on traditional machine-learning algorithms or deep learning algorithms with unsatisfied results. In this study, we proposed an ensemble of pre-trained convolutional neural networks to classify brain tumors into three types from their T1-weighted contrast-enhanced MRI (CE-MRI) images, which are meningioma, glioma, and pituitary tumor. Three pre-trained convolutional neural networks (Inception-v3, Resnet101, Densenet201) with the best classification performance (i.e. accuracy of 96.21%, 97.00%, 96.54%, respectively) on the CE-MRI benchmark dataset were selected as backbones of the ensemble model. The features extracted by backbone networks in the ensemble model were further classified by a support vector machine.

Results:

The ensemble system achieved an average classification accuracy of 98.14% under a five-fold cross-validation process, outperforming any single deep learning model in the ensemble system and other methods in the previous studies. Performance metrics for each brain tumor type, including area under the curve, sensitivity, specificity, precision, and F-score, were calculated to show the ensemble system’s performance. Our work addressed a practical issue by evaluating the model with fewer training samples. The classification accuracy was reduced to 97.23%, 96.87%, and 93.96% when 75%, 50%, and 25% training data was used to train the ensemble model, respectively.

Conclusion:

Our ensemble model has a great capacity and achieved the best performance in any single convolutional neural networks for brain tumors classification and is potentially applicable in real clinical practice.
Removal of a Periarticular Cyst of the Hip Joint Using an Ultrasoundbased
Minimally Invasive Technique — A Case Report
Authors: Konarski Wojciech , Poboży Tomasz
Published: April 2022

Introduction:

Cystic lesions protruding into surrounding anatomical structures may decrease
quality of life.

Case presentation:

In our case, the cyst was located periarticularly which indicated a potential need
for open surgery. We used ultrasound-based minimally invasive arthroscopy technique. A 39-year-oldwoman’s
ultrasonographic examination revealed delamination of the acetabular labrum and periarticular
cyst located extra-articularly, compressing the iliopsoas muscle. The ultrasound-guided complete
removal of the cyst was performed using a shaver blade placed into its lumen through the skin incision.
The acetabular labral tear was treated with a classic arthroscopy procedure. 5 weeks after the surgery,
the patient reported no pain and no functional impairment was detected.

Conclusion:

A well-known ultrasound diagnostic technique can save patients from more invasive procedures
and can be beneficial for the surgeons.
MRI Breast: Current Imaging Trends, Clinical Applications, and Future
Research Directions
Authors: Rahmat Kartini , Mumin Nazimah Ab , Hamid Marlina Tanty Ramli , Hamid Shamsiah Abdul , Ng Wei Lin
Published: April 2022

Magnetic Resonance Imaging (MRI) is the most sensitive and advanced imaging technique
in diagnosing breast cancer and is essential in improving cancer detection, lesion characterization, and
determining therapy response. In addition to the dynamic contrast-enhanced (DCE) technique, functional
techniques such as magnetic resonance spectroscopy (MRS), diffusion-weighted imaging
(DWI), diffusion kurtosis imaging (DKI), and intravoxel incoherent motion (IVIM) further characterize
and differentiate benign and malignant lesions thus, improving diagnostic accuracy.
There is now an increasing clinical usage of MRI breast, including screening in high risk and supplementary
screening tools in average-risk patients. MRI is becoming imperative in assisting breast surgeons
in planning breast-conserving surgery for preoperative local staging and evaluation of neoadjuvant
chemotherapy response. Other clinical applications for MRI breast include occult breast cancer
detection, investigation of nipple discharge, and breast implant assessment. There is now an abundance
of research publications on MRI Breast with several areas that still remain to be explored.
This review gives a comprehensive overview of the clinical trends of MRI breast with emphasis on
imaging features and interpretation using conventional and advanced techniques. In addition, future
research areas in MRI breast include developing techniques to make MRI more accessible and costeffective
for screening. The abbreviated MRI breast procedure and an area of focused research in the
enhancement of radiologists' work with artificial intelligence have high impact for the future in MRI
Breast.
Phenolic Compounds of Fig (Ficus carica L.) Leaves: Optimization of
Extraction by Response Surface Methodology and UPLC-MS Phytochemical
Characterization
Authors: Bachir-bey Mostapha , Yahiaoui Sonia , Kati Djamel Edine , Chaalal Makhlouf , Otmani Amar , Bettache Nadir
Published: April 2022

Background:

This study is based on ethnobotanical observation and traditional medicinal utilization of fig (Ficus carica L.) by southwest Asian and Mediterranean populations.

Objective:

Considering phenolics among the highly bioactive compounds for their numerous therapeutic applications, the first goal of this investigation is the optimization of their recovery by using Response Surface Methodology (RSM).

Methods:

Prior to RSM, the single-factor method was applied for revealing the main factors influencing the extraction (solvent type, solvent concentration, sample˗to˗solvent ratio, temperature, and time of extraction). After using the optimal conditions of extraction, the second objective was the identification of fig leave phytochemicals by UPLC˗MS.

Results:

The results of preliminary optimization step through sequential methodology revealed that solvent concentration, extraction duration, and temperature, and were the main influencing factors. All these tested extraction parameters influenced significantly total phenolic contents (TPC) and DPPH-free radical scavenging activity (FRSA). RSM analysis using Box˗Behnken design showed that the optimal extraction conditions of total phenolic contents of fig leaves were 23.07% acetone, 51.82 °C, and 118.02 min with values of 29.44 mg GAE/g and 59.48% for TPC and FRSA, respectively. Eight phenolic compounds were detected including chlorogenic, caffeic, and coumaric acids, rutin, isoquercetin, luteolin, quercetin, and kaempferol well known for their bioactivities. Two non˗phenolic compounds were also found: The psoralen and an oxylipin, the 9˗oxo˗octadecadienoic acid that was detected for the first time in fig leaves.

Conclusion:

Through sequential and RSM optimization processes for phenolic antioxidants of Ficus carica leaves, the developed mathematic models have expressed a high level of significance. The UPLC-MS analysis of the optimal extract revealed numerous phenolic compounds known for their bioactivities.
Medications Associated with Occurrence of Urinary Tract Infections in
Patients with Diabetes, Heart Failure or Both
Authors: Hill Joseph Ben , Fixen Cy , Wright Garth , Saseen Joseph J.
Published: April 2022

Background:

Evidence broadly identifying medications newly-initiated prior to the occurrence
of a urinary tract infection (UTI) in patients with diabetes, heart failure, or both of these
conditions is lacking.

Objective:

The aim was to broadly assess medication filling patterns and incidence of UTIs to
identify medications or medication classes most frequently initiated prior to UTI occurrence.

Methods:

This retrospective study utilizing a national claims database examined medications
commonly initiated in the six months preceding a UTI in patients with diabetes and/or heart failure.
Patients with a new diagnosis of UTI, a diagnosis of diabetes and/or heart failure, continuous enrollment
in the database for at least 12 months prior to the index UTI occurrence, and who initiated
at least one new medication in the 6 months preceding the index UTI were evaluated.

Results:

12,744 patients met criteria: 10,626 (83.4%) had a diagnosis of diabetes, 838 (6.6%) had a
diagnosis of heart failure, and 1,280 (10.0%) had diagnoses for both. Opioids were the most commonly
filled medication class among all three groups. Medications from the SGLT2i class were the
twelfth, eleventh, and eighteenth most common medications filled prior to the index UTI for all patients,
patients with diabetes, and patients with diabetes and heart failure, respectively.

Conclutions:

Opioids were by far the most commonly initiated medication class in the 6 months
prior to UTI incidence in patients with diabetes and/or heart failure. SGLT2i medications were not
commonly initiated in the 6 months prior to the occurrence of a UTI.
Repurposing Disulfiram as a Chemo-Therapeutic Sensitizer: Molecular Targets and
Mechanisms
Authors: Sun Feilong , Wang Hongzhi , Nie Jinfu , Hong Bo
Published: April 2022

Currently, chemotherapy is still the main strategy for cancer treatment. However, chemotherapy resistance
remains a challenge. Disulfiram (DSF) is an FDA-approved medicine for the treatment of alcoholism; however, it was
later revealed to have anticancer properties. Importantly, numerous studies have shown that DSF can be employed as a
chemotherapeutic sensitizer to enhance the anticancer efficacy of chemo-drugs in a variety of cancers. Furthermore, the
combinations of DSF and chemo-drugs have been tested in clinical trials. In the review, we summarized the possible
molecular targets and mechanisms of DSF to reverse chemo-resistance. We also further discussed the opportunities and
challenges of DSF as a chemo-therapeutic sensitizer. In conclusion, DSF could be a potentially repurposed drug that
sensitizes cancer cells to chemotherapy in the clinic.
Effect of Curcumin on the Head and Neck Squamous Cell Carcinoma Cell Line HN5
Authors: Sharifi Simin , Khan Haroon , Abdolahinia Elaheh Dalir , Ahmadian Shahin , Bohlouli Sepideh , Gharehbagh Faezeh Jafarmadar , Jahandizi Negar Ghorbani , Vahed Sepideh Zununi , Saadat Yalda Rahbar , Aghbali Amirala , Dizaj Solmaz Maleki , Alsharif Khalaf F.
Published: April 2022

Background:

Curcumin has been isolated from the rhizomes of Curcuma longa. Over the years, it has shown outstanding therapeutic potential in various human disorders, including cancers.

Objective:

The aim is to study curcumin’s effects on the apoptosis signaling pathway in the head and neck squamous cell carcinoma (HNSCC) cell line HN5.

Methods:

The cytotoxicity of curcumin on HN5 cells were assessed. In addition, HN5 cells were also treated with curcumin to evaluate its effect on the caspase-8, -9, Bcl-2, Bax, and Stat3 gene expressions.

Results:

The results exhibited that cell viability reduced following curcumin treatment in a concentration- dependent manner. Curcumin treatment caused decreased expression of Bcl2, with simultaneous upregulation of the Bax/Bcl2 ratio. Curcumin increased caspase-9 expression, did not affect caspase-8, and decreased Stat3 expression. The induction of the mitochondria-dependent apoptosis pathway of curcumin happened by modulating the expression of Bcl2 and Bax genes, resulting in the caspase-9 activation. Furthermore, curcumin decreased the expression of the Stat3 in HN-5 cells.

Conclusions:

In conclusion, curcumin showed marked anticancer effects in the HN-5 cell line by modulating Stat-3; Bax/Bcl-2 expression in vitro.
Resveratrol Augments Doxorubicin and Cisplatin Chemotherapy: A Novel
Therapeutic Strategy
Authors: Zarrabi Ali , Bishayee Anupam , Mirzaei Sepideh , Gholami Mohammad Hossein , Zabolian Amirhossein , Saleki Hossein , Bagherian Morteza , Torabi Seyed Mohammadreza , Sharifzadeh Seyed Omid , Hushmandi Kiavash , Fives Kaila R. , Khan Haroon , Ashrafizadeh Milad
Published: April 2022

Background:

The treatment of cancer is a current challenge for public health, causing high rates of morbidity and mortality around the world. Doxorubicin (DOX) and cisplatin (CP) are two well-known chemotherapeutic agents approved by the Food and Drug Administration for the treatment of cancer patients. However, there are two problems associated with DOX and CP, namely, drug resistance and adverse impact. Resveratrol (Res) belongs to the stilbene class and possesses a variety of health-promoting effects, such as antioxidant, an-ti-inflammatory, anticancer, hepatoprotective, and neuroprotective effects.

Objective:

The aim of the present review is to give special attention towards the therapeutic impacts of Res in potentiating DOX and CP’s antitumor activities as well as reducing their side effects.

Methods:

PubMed, Science Direct, and Google Scholar were used to search articles for the current manuscripts.

Results:

Co-administration of Res can prevent chemoresistance and potentiate the induction of apoptosis as well as cell cycle arrest in cancer cells. Res can enhance the sensitivity of can-cer cells to DOX and CP chemotherapy, via inhibiting the migration and metastasis of cancer cells. Simultaneously, Res, owing to its therapeutic actions, ameliorates the adverse impacts of DOX and CP on normal cells and organs, including the liver, kidney, brain, and testes. As Res suffers from poor bioavailability, to improve its antitumor activity and protective effects, nanoformulations have been developed with promising results.

Conclusion:

Conclusion: Based on preclinical studies, it is obvious that Res is a promising adjuvant for CP and DOX chemotherapy and its benefits can be utilized in the clinical course.
Oxytocin Release: A Remedy for Cerebral Inflammaging
Authors: Buemann Benjamin
Published: April 2022

Oxytocin facilitates reproduction both by physiological and behavioral mechanisms. Oxytocinergic neurons emerging from the hypothalamus release oxytocin from the pituitary gland to the blood by axonal discharge to regulate reproductive organs. However, at the same time, oxytocin is secreted into neighboring areas of the hypothalamus from the dendrites of these neurons. Here, the peptide acts by autocrine and paracrine mechanisms to influence other neuroendocrine systems. Furthermore, oxytocinergic neurons project to many different locations in the brain, where they affect sensory processing, affective functions, and reward. Additional to its regulatory role, significant anti-inflammatory and restoring effects of oxytocin have been reported from many invivo and in-vitro studies. The pervasive property of the oxytocin system may enable it generally to dampen stress reactions both peripherally and centrally, and protect neurons and supportive cells from inadequate inflammation and malfunctioning. Animal experiments have documented the importance of preserving immune- and stem cell functions in the hypothalamus to impede age-related destructive processes of the body. Sexual reward has a profound stimulating impact on the oxytocinergic activity, and the present article therefore presents the hypothesis that frequent sexual activity and gratigying social experiance may postpone the onset of frailty and age-associated diseases by neural protection from the bursts of oxytocin. Furthermore, suggestions are given how the neuroplastic properties of oxytocin may be utilized to enhance sexual reward by learning processes in order to further reinforce the release of this peptide.