bluuebunny/crossref_metadata_2025 huggingface dataset:
Cholecystokinin B Receptor Agonists Alleviates Anterograde Amnesia in CCK-deficient and Aged Alzheimer's Disease Mice
Authors: Zhang Nan , Sui Yixuan , Jendrichovsky Peter , Feng Hemin , Shi Heng , Zhang Xu , Xu Shenghui , Sun Wenjian , Zhang Huatang , Chen Xi , Tortorella Micky D , He Jufang
Published: September 2023

Background As one major symptom of Alzheimer’s disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD.Methods mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK−/−) mice. Animals’ cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation.Results Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK−/− mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists.Conclusions Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.
Reliability analysis of three-dimensional reinforced slope considering the spatial variability in soil parameters
Authors: Wang Yuke , Shao Linlan , Wan Yukuai , Chen Hao
Published: September 2023

In this paper, a procedure is proposed for calculating the reliability of three-dimensional reinforced slopes, taking into consideration the spatial variability of soil strength parameters. An ellipsoidal sliding surface is utilized as an approximate substitute for the actual sliding surface. The Karhunen–Loève (KL) expansion method is employed to generate random fields. The safety factor of the reinforced slope is determined using the Bishop method, and the reliability is evaluated through the Monte Carlo method. Based on the procedure, the effects of different reinforcement parameters and random parameters on the mean safety factor and failure probability of three-dimensional slopes are studied and compared with the results of two-dimensional slopes. It is observed that slope reliability is significantly improved by the implementation of the upper sparse and lower dense reinforcement scheme, leading to a notable 38.4% reduction in failure probability and a 2.4% increase in the safety factor. Additionally, an effective means of enhancing slope reliability is found to be the increase in the length and number of reinforcement layers. The reliability of 3D reinforced slopes is notably influenced by the spatial variability of soil strength parameters. The degree of influence of autocorrelation distance on the failure probability is ranked as lz > lx > ly. When lz increases from 1m to 5m, the failure probability is increased by 221.85%, from 5.4–17.38%. As the correlation coefficient r(c, φ) increases from − 0.7 to -0.3, the failure probability is increased by 26.7%. The comparison with 2D reinforced slopes reveals that 3D reinforced slopes demonstrate a higher safety factor and a lower failure probability. As a result, slope reliability is tended to be underestimated by the 2D slope analysis.
Comparison of estimated GFR using cystatin C versus creatinine in pediatric kidney transplant recipients
Authors: Pizzo Helen , Nguyen John , Schwartz George J , Wesseling-Perry Katherine , Ettenger Robert , Chambers Eileen Tsai , Weng Patricia
Published: September 2023

Background
An accurate, rapid estimate of glomerular filtration rate (GFR) in kidney transplant patients affords early detection of transplant deterioration and timely intervention. This study compared the performance of serum creatinine (Cr) and cystatin C (CysC)-based GFR equations to iohexol GFR (iGFR) among pediatric kidney transplant recipients.
Methods
CysC, Cr, and iGFR were obtained from 45 kidney transplant patients, 1–18 years old. Cr- and CysC-estimated GFR (eGFR) was compared against iGFR using the Cr-based (Bedside Schwartz, U25-Cr), CysC-based (Gentian CysC, CAPA, U25-CysC), and Cr-CysC combination (CKiD Cr-CysC, U25 Cr-CysC) equations in terms of bias, precision, and accuracy. Bland-Altman plots assessed the agreement between eGFR and iGFR. Secondary analyses evaluated the formulas in patients with biopsy-proven histological changes, and K/DOQI CKD staging.
Results
U25-CysC and Gentian CysC equations had the smallest bias. 88.9% of U25-CysC and 82.2% of Gentian CysC estimations were within 30% iGFR; 37.8% of both and 40% of CKiD Cr-CysC were within 10% iGFR. In subjects with histological changes on biopsy, U25-CysC and Gentian CysC had the smallest bias and were most accurate - both with 83.3% of and 41.7% of estimates within 30% and 10% iGFR, respectively. U25-CysC, CKiD Cr-CysC, and U25 Cr-CysC, were the most precise. Bland-Altman plots show the Bedside Schwartz, Gentian CysC, CAPA, and U25-CysC tend to overestimate GFR when > 100 ml/min/1.72m2. CAPA misclassified CKD stage the least (whole cohort 24.4%, histological changes on biopsy 33.3%).
Conclusion
In this small cohort, CysC-based equations appear to have better bias, precision, and accuracy in predicting GFR.
Calibrated Explanations for Regression
Authors: Löfström Tuwe , Löfström Helena , Johansson Ulf , Sönströd Cecilia , Matela Rudy
Published: September 2023

Artificial Intelligence (AI) is often an integral part of modern decision support systems (DSS). The best-performing predictive models used in AI-based DSS lack transparency. Explainable Artificial Intelligence (XAI) aims to create AI systems that can explain their rationale to human users. Local explanations in XAI can provide information about the causes of individual predictions in terms of feature importance. However, a critical drawback of existing local explanation methods is their inability to quantify the uncertainty associated with a feature's importance. This paper introduces an extension of a feature importance explanation method, Calibrated Explanations (CE), previously only supporting classification, with support for standard regression and probabilistic regression, i.e., the probability that the target is above an arbitrary threshold. The extension for regression keeps all the benefits of CE, such as calibration of the prediction from the underlying model with confidence intervals, uncertainty quantification of feature importance, and allows both factual and counterfactual explanations. CE for standard regression provides fast, reliable, stable, and robust explanations. CE for probabilistic regression provides an entirely new way of creating probabilistic explanations from any ordinary regression model, allowing dynamic selection of thresholds. The performance of CE for probabilistic regression regarding stability and speed is comparable to LIME. The method is model agnostic with easily understood conditional rules. An implementation in Python is freely available on GitHub and for installation using both pip and conda, making the results in this paper easily replicable.
Characterizations of a New Generalized Family of Distributions
Authors: Maswadah M.
Published: September 2023

This paper introduces a new family that extends some lifetime distributions, such as the Weibull, inverse Weibull, Lomax, logistic, and log-logistic distributions, which could be applied in several fields, especially to fit lifetime data. This family has a monotonically increasing and decreasing hazard rate. Some characteristics of one of these distributions, such as the Weibull-Logistic distribution, have been studied, including the hazard rate function, quantile function, moments, and distribution of the order statistics. Three real data sets have been studied that show this distribution can be used quite effectively in fitting and analyzing real lifetime data and provides a better fit than other well-known lifetime models such as Weibull, inverse Weibull, and log-logistic distributions. Finally, Monte Carlo simulations have been carried out to calculate the asymptotic confidence bounds for the distribution parameters.
Mercury Speciation in Highly Contaminated Soils from Chlor‐Alkali Plants Using Chemical Extractions
Authors: Neculita Carmen‐Mihaela , Zagury Gérald J. , Deschênes Louise
Published: September 2023

A four‐step novel sequential extraction procedure (SEP) was developed to assess Hg fractionation and mobility in three highly contaminated soils from chlor‐alkali plants (CAPs). The SEP was validated using a certified reference material (CRM) and pure Hg compounds. Total, volatile, and methyl Hg concentrations were also determined using single extractions. Mercury was separated into four fractions defined as water‐soluble (F1), exchangeable (F2) (0.5 M NH4Ac–EDTA and 1 M CaCl2 were tested), organic (F3) (successive extractions with 0.2 M NaOH and CH3COOH 4% [v/v]), and residual (F4) (HNO3 + H2SO4 + HClO4). The soil characterization revealed extremely contaminated (295 ± 18 to 11 500 ± 500 mg Hg kg−1) coarse‐grained sandy soils having an alkaline pH (7.9–9.1), high chloride concentrations (5–35 mg kg−1), and very low organic carbon content (0.00–18.2 g kg−1). Methyl Hg concentrations were low (0.2–19.3 μg kg−1) in all soils. Sequential extractions indicated that the majority of the Hg was associated with the residual fraction (F4). In Soils 1 and 3, however, high percentages (88–98%) of the total Hg were present as volatile Hg. Therefore, in these two soils, a high proportion of volatile Hg was present in the residual fraction. The nonresidual fraction (F1 + F2 + F3) was most abundant in Soil 1 (14–42%), suggesting a higher availability of Hg in this soil. The developed and validated SEP was reproducible and efficient for highly contaminated samples. Recovery ranged between 93 and 98% for the CRM and 70 and 130% for the CAP‐contaminated soils.
Health risk assessment of nitrate pollution of drinking groundwater in rural areas of Suihua, China
Authors: Sun Qifa , Yang Ke , Liu Tao , Yu Junbo , Li Chunhai , Yang Dexian , Hu Chen , Guo Lin
Published: September 2023

In order to investigate the health risks of NO3− in rural drinking groundwater in Suihua, China and provide a basis for healthy drinking water, 40 sets of groundwater samples were collected in the Suihua area, and the average concentration of nitrate in the study area was 71.66 mg/L, statistical analysis software (SPSS19), Hydrogeochemical Analysis Software (AqQA) and groundwater pollution analysis software were used. Through water sample collection, chemical analysis and construction of human health risk model (HHRA), a qualitative and quantitative assessment of NO3− health risk was carried out for people of different ages and sexes, and it was concluded that there was NO3− pollution health risk in rural drinking groundwater in Suihua. Health risk level: infants > children > adult females > adult males. The evaluation provides a scientific basis for the prevention and control of NO3− pollution in groundwater and new ideas for preventing human health risks.
Correlation between wastewater and COVID-19 case incidence rates in major California sewersheds across three variant periods
Authors: Rabe Angela , Ravuri Sindhu , Burnor Elisabeth , Steele Joshua A. , Kantor Rose S. , Choi Samuel , Forman Stanislav , Batjiaka Ryan , Jain Seema , León Tomás M. , Vugia Duc J. , Yu Alexander T.
Published: September 2023

Monitoring for COVID-19 through wastewater has been used for adjunctive public health surveillance, with SARS-CoV-2 viral concentrations in wastewater correlating with incident cases in the same sewershed. However, the generalizability of these findings across sewersheds, laboratory methods, and time periods with changing variants and underlying population immunity has not been well described. The California Department of Public Health partnered with six wastewater treatment plants starting in January 2021 to monitor wastewater for SARS-CoV-2, with analyses performed at four laboratories. Using reported PCR-confirmed COVID-19 cases within each sewershed, the relationship between case incidence rates and wastewater concentrations collected over 14 months was evaluated using Spearman's correlation and linear regression. Strong correlations were observed when wastewater concentrations and incidence rates were averaged (10- and 7-day moving window for wastewater and cases, respectively, ρ = 0.73–0.98 for N1 gene target). Correlations remained strong across three time periods with distinct circulating variants and vaccination rates (winter 2020–2021/Alpha, summer 2021/Delta, and winter 2021–2022/Omicron). Linear regression revealed that slopes of associations varied by the dominant variant of concern, sewershed, and laboratory (β = 0.45–1.94). These findings support wastewater surveillance as an adjunctive public health tool to monitor SARS-CoV-2 community trends.
Hydroclimatic trends, breakpoints and future projection analysis of the Ogun River Basin in West Africa
Authors: Ojelabi Oluwatoyin , Hounkpè Jean , Oluwasemire Kolapo Olatunji , Lawin Agnidé Emmanuel
Published: September 2023

Trend analysis is important to understand the performance and features of hydrological variables over a long-time scale. This study analyses the hydroclimatic trends in precipitation, temperature (minimum and maximum) data from seven synoptic stations and river discharge from three outlets that were investigated between 1984–2019 and projected between 2020–2060 over the Ogun River Basin. The results of the trend analysis showed a non-significant positive trend in precipitation and a significant positive trend (p,0.05 and p,0.01 significant trends) in maximum and minimum temperatures. The discharge reveals a non-significant positive trend on the annual scale while a significant decreasing trend in the dry season. The annual rainfall projection is expected to increase by 1.3% under RCP 2.6 and 1.4% under RCP 8.5 by 2060. The mean annual temperature is expected to increase between 1.5-2.5 °C under RCP 2.6 and 2-3.5 °C under RCP 8.5 by 2060, respectively. The variations in discharge without significant changes in rainfall suggested other variables were influencing the discharge. These could be changes in river basin physical elements such as alterations in the dynamics of land use land cover changes. The findings of this study can be used for strategizing adaptation and mitigation measures for water resources management.
3D numerical simulation of the separation zone at the channel–pipe junction
Authors: Sun Bin , Feng Linqin , Li Zhiwei , Song Zhanqi , Li Cheng
Published: September 2023

At the confluence zone, the separation zone affects the flow, pollutant transport, and damages the bed and sidewalls of the channel. In this research, the geometric characteristics of the separation zone and the tailwater effect at the 90° channel–pipe junction are investigated using experiments and numerical simulations. These characteristics are different from the previous study in the channel or river junctions. (1) The separation zone is not attached to the sidewall of the channel. The shape of the separation zone is close to an ellipse but there is depression at the inside of the separation zone. (2) There is a pair of helical cells with opposite flow directions near the sidewall, which affects the shape of the separation zone and results in the differences. (3) The volume of the separation zone is proportional to the discharge ratio and the water-surface height. Furthermore, it's found that the momentum ratio is the basic reason affecting the volume of the separation zone. (4) The tailwater effect is affected by the discharge ratio and the water-surface height. And there is a significant positive correlation between the volume of separation zone and tailwater effect.
contexto do Mestrado Profissional em Química em rede nacional:
Authors: Gonzaga Glaucia , Paiva Daniel , Eichler Marcelo
Published: September 2023

Este artigo se trata de um recorte de uma pesquisa de doutorado e tem por objetivo identificar as correlações do Mestrado Profissional em Química em Rede Nacional (PROFQUI) na formação docente com o princípio de aplicabilidade proposto por Michael Gibbons. Para tal foi realizado um estudo bibliográfico e documental por meio de documentos oficiais do PROFQUI dispostos em seu site principal, que foram analisados de forma qualitativa quanto às correspondências com o princípio de aplicabilidade proposto no Modo 2 de produção de conhecimento, em quatro características: (i) o contexto da aplicação; (ii) o contexto do problema; (iii) o contexto real; e (iv) a finalidade social. Essa proposta considera o contexto da aplicação do conhecimento como um sistema integrador de dinâmica flexível e sua finalidade social real; permitindo às instituições de ensino identificar lacunas na formação dos alunos, adequando a execução de suas atividades. Os resultados indicam que há consideráveis relações entre o Modo 2 e o PROFQUI no que diz respeito à aplicabilidade, já que em ambos há a procura pelo atendimento de uma demanda real da sociedade/comunidade e obtenção de resultados por meio de produtos da pesquisa (produto educacional) aplicados em situações pontuais.
Epidemiology of Traumatic Brain Injury in Abu-Dhabi, UAE
Authors: Alqaydi Khalifa , Ghazanfar Omar , Madhi Amal , Avila Norman , Fares Saleh
Published: September 2023

Background:

Trauma is a leading cause of death around the world, and patients who suffer traumatic brain injuries (TBI) have a worse prognosis and are at a higher probability of death compared to other trauma patients. The sheer burden of TBI on personal, social, and economic aspects of life is daunting. However, the available updated literature for UAE documenting the characteristics of TBI comprehensively is lacking. Hence, this study was conducted to understand the extent of TBI in order to encourage new policies and regulations, enhance existing programs or start new initiatives to reduce associated morbidities and mortalities.

Methods:

Our study involved a sample of 998 entries extracted from the Abu-Dhabi trauma registry between December 2018 and December 2020. Patients with TBI who died on arrival or were hospitalized for more than 24 hours were included in the study.

Results:

A total of 80% of our patients were males aged 40 years or below. The most common causes of head trauma were motor vehicle accidents and fall from heights. Most patients spent 10 days or less in the hospital. Patients who developed a disability after the injury were about 5%. The percentage of patients who led to death in our sample was 6 percent.

Conclusion:

Most TBIs are preventable through targeted public education and awareness programs where the target population is educated and aware of the safety precautions while driving, biking, doing blue-collar jobs, or hiking. Enforcing rules for traffic and labor safety also has another major preventative rule.
Antiviral Compounds to Address Influenza Pandemics: An Update
from 2016-2022
Authors: Romeo Roberto , Legnani Laura , Chiacchio Maria Assunta , Giofrè Salvatore V. , Iannazzo Daniela
Published: September 2023

In recent decades, the world has gained experience of the dangerous effects of
pandemic events caused by emerging respiratory viruses. In particular, annual epidemics
of influenza are responsible for severe illness and deaths. Even if conventional influenza
vaccines represent the most effective tool for preventing virus infections, they are not
completely effective in patients with severe chronic disease and immunocompromised and
new small molecules have emerged to prevent and control the influenza viruses. Thus, the
attention of chemists is continuously focused on the synthesis of new antiviral drugs able
to interact with the different molecular targets involved in the virus replication cycle. To
date, different classes of influenza viruses inhibitors able to target neuraminidase enzyme,
hemagglutinin protein, Matrix-2 (M2) protein ion channel, nucleoprotein or RNAdependent
RNA polymerase have been synthesized using several synthetic strategies
comprising the chemical modification of currently used drugs. The best results, in terms
of inhibitory activity, are in the nanomolar range and have been obtained from the chemical
modification of clinically used drugs such as Peramivir, Zanamivir, Oseltamir,
Rimantadine, as well as sialylated molecules, and hydroxypyridinone derivatives. The aim
of this review is to report, covering the period 2016-2022, the most recent routes related to
the synthesis of effective influenza virus inhibitors.
Pharmacological activities of turmerones
Authors: Niknejad Amirhossein , Hosseini Yasamin , Najafi Arab Zahra , Razavi Seyed Mehrad , Momtaz Saeideh , Sathyapalan Thozhukat , Majeed Muhammed , Jamialahmadi Tannaz , Abdolghaffari Amir Hossein , Sahebkar Amirhossein
Published: September 2023

Turmerones are major bioactive compounds of Curcuma species with several beneficial pharmacological activities. In addition, various in vivo and in vitro studies noted that turmerones could affect different cytokines, metabolic pathways, and targets. Turmerones will have the potential to be a candidate agent to lessen many pathological and immunological conditions as a result of these pharmacological activities. In this review, we provided information about the pharmacological actions of turmerones using search engines such as PubMed, Google Scholar, Scopus, and Web of Science.
The Design and Applications of 1,8-naphthalimide-poly(amidoamine) Dendritic
Platforms
Authors: Luo Fangfang , Luo Xin , Wang Le , Qu Yi , Yin Xue-Bo
Published: September 2023

Poly(amidoamine) (PAMAM) is easily prepared with ethylenediamine as the
precursor to form a dendritic structure with a size of 1.4 -11.4 nm from generation 1 to
10. The terminal amino groups of PAMAM could be grafted active species, such as
1,8-naphthalimide (NI) or its derivatives, to integrate their photophysical properties
into PAMAM as NI-PAMAM. With/without metals, the new dendritic platforms can be
found for different applications, including but not limited to sensing, imaging, antibacterial,
anticancer, and liquid crystal and battery matrix. By controlling the different
generations of dendrimers, the precise size less than 10 nm can be realized. In this review,
we a) provide an overview of the 1,8-naphthalimide-poly(amidoamine) dendritic platforms and b) prospect
that functionalized dendrimers (high algebra) could act as “nanoparticles” with the precise size to bridge the gap
between functional molecules and real nanoparticles.
Lncrna CASC15 Activated By TCF12 Promote Colorectal Cancer
Progression via EMT
Authors: Yan Shuai , Yuan Ming , Yang Xichen , Huang Xianting , Wu Dan , Wang Nanyao , Sun Xia , Qin Ya , Fei Yanhua , Zhao Zhenguo , Wang Qiong
Published: September 2023

Background:

Colorectal cancer (CRC) is one of the most common gastrointestinal malignancies.
LncRNA CASC15 has also been found to play a vital role in malignant tumors.

Objective:

Our objective is to explore the role of CASC15 in colorectal cancer and its regulation of
EMT and to clarify the reasons for its up-regulated expression in CRC.

Methods:

Quantitative real-time PCR was performed to evaluate the expression of CASC15 in
CRC. The biology function of CASC15 on CRC was assessed by in vitro experiments, including
CCK8, colony formation, transwell assays and flow cytometry. Luciferase reporter assays were
used to confirm the regulation between TCF12 and CASC15. Quantitative real-time PCR and
western blot analysis were used to evaluate the biomarkers associated with epithelial-mesenchymal
transition (EMT).

Results:

We found that CASC15 was remarkably upregulated in CRC and positively correlated
with poorer relapse-free survival. CASC15 knockdown significantly suppressed the proliferation
and migration of CRC. Furthermore, CASC15 downregulation mediated apoptosis of CRC. Mechanistically,
TCF12 activates CASC15 transcription to mediate its up-regulation, which activates
EMT and promotes CRC progression.

Conclusion:

Our study identified TCF12/CASC15/EMT as a new regulatory signal axis of CRC.
CASC15 may be a new molecular marker and target for CRC.
Synthesis and In Silico Studies of Quinazolinones as PARP-1 Inhibitors
Authors: Guleria Maneesh , Kumar Adarsh , Singh Ankit Kumar , Kumar Pradeep
Published: September 2023

Background:

Cancer is a leading threat to humankind, accounting for nearly one million
deaths in 2018, and the expected number of cancer-related deaths in 2040 is more than 16 million.
The most common causes of cancer deaths are lung, colorectal, stomach, liver and breast cancer,
while the highest number of new cancer cases belong to lung, breast, colorectal, prostate, stomach
and liver cancer.

Introduction:

PARP-1 is an enzyme that plays an important role in DNA repair, cell propagation/survival
and death due to its influence on numerous biological processes. Quinazolinones represent an important
scaffold in medicinal chemistry and have a broad spectrum of biological activities.

Methods:

In this study, we have synthesized quinazolinones by reaction of 2-aminobenzamide and
substituted aldehydes. Molecular docking studies of synthesized compounds were performed for
their PARP-1 binding affinities using Schrodinger 2016 software. In silico ADME studies were also
performed for the synthesized compounds using the QikProp tool of Schrodinger software.

Results:

Results of molecular docking studies indicated that synthesized quinazolinones had a
good affinity towards active site of PARP-1 and compound 4 had the best docking score (-10.343).
Results of ADME studies indicated the drug-like properties of synthesized compounds, which
make them suitable drug candidates.

Conclusion:

All the synthesized compounds have a better docking score than niraparib (-9.05).
Further, the synthesized compounds have a favorable ADME profile. Therefore, they may serve as
important leads in discovering PARP-1 inhibitors.
Concomitant Expression of CD39, CD69, and CD103 Identifies Antitumor
CD8+ T Cells in Breast Cancer Implications for Adoptive Cell Therapy
Authors: Lama Grace Ivonne Gattas , Noél Gregory , Márquez Francisco Carlos  López , Galarza Faviel Francisco  González , Hinojosa Adria Imelda Prieto , Rivera Lydia Enith Nava , Willard-Gallo Karen , Astorga Jesús Rafael Arguëllo
Published: September 2023

Background:

In cancer, an effective immune response involves the action of several
different cell types, among which CD8 T cells play a major role as they can specifically recognize
and kill cancer cells via the release of cytotoxic molecules and cytokines, being of major importance
for adoptive cell transfer (ACT) of ex vivo expanded tumor-infiltrating lymphocytes
(TILs). The inflammation resulting from the tumor growth attracts both activated and bystander T
cells. For an effective antitumor response, the T cell must express a specific group of chemokine
receptors and integrins which include CD103, CD39, CD69, and CD25. These markers had already
been analyzed in various cancers, not including breast cancer and their subsequent subtypes,
until now. To analyze, the key receptors on ex vivo expanded tumor-infiltrating lymphocytes in
luminal A and luminal B breast cancer (BC) subtypes.

Materials and Methods:

We were successful in expanding TILs ex vivo using a standard TIL culture
condition from a cohort study of 15 primary luminal A and luminal B breast cancer patients.
Furthermore, we examined the expression of CD103, CD39, CD69, and CD25 biomarkers after
the expansion by flow cytometry.

Results:

We found that the information about the percentage of TILs obtainable after the ex vivo
expansion is not associated to nor it is dependent on the heterogeneity of the TIL population before
the expansion and does not differ by the molecular subtype (p>0.05). We also found that there
is a major population of memory-resident antitumor CD8+CD103+CD39+ and CD8+CD103+
CD69+ TILs present in the stroma after the expansion when compared to CD4 immunosubtypes
(p< 0.0001). Only the CD8+CD103+CD39+ subpopulation was related to BC subtype (0.0009).

Conclusion:

Evidence from our study suggests that CD8 TILs present in the stroma of luminal A
and luminal B breast cancer patients can be quantified and phenotyped by flow cytometry and be
further expanded ex vivo. The immuno-phenotyping of these markers may be targeted to improve
the success of immunotherapeutic approaches, such as adoptive cellular therapy (ACT) in patients
with BC.
Nanostructured Lipid Carriers Mediated Drug Delivery to Posterior
Segment of Eye and their In-vivo Successes
Authors: Singh Amit Kumar , Kumar Manish , Upadhyay Prabhat Kumar
Published: September 2023

Background:

The disease of the posterior segment of the eye is a major concern
worldwide, and it affects more than 300 million people and leads to serious visual deterioration.
The current treatment available is invasive and leads to serious eye complications. These shortcomings
and patient discomfort lead to poor patient compliance. In the last decade, Nanostructured
lipid carriers (NLC) have established a remarkable milestone in the delivery of drug substances to
the posterior segment of the eye. Additionally, NLC can reduce the clearance due to adhesive
properties which are imparted due to nano-metric size. This attribute might reduce the adverse
effects associated with intravitreal therapy and thus enhance therapeutic efficacy, eventually raising
patient adherence to therapy. The current review provides an inclusive account of NLC as a
carrier to target diseases of the posterior segment of the eye.

Objective:

The review focuses on the various barrier encountered in the delivery of drugs to the
posterior segment of the eye and the detail about the physicochemical property of drug substances
that are considered to be suitable candidates for encapsulation to lipid carriers. Therefore, a plethora
of literature has been included in this review. The review is an attempt to describe methods
adopted for assessing the in-vivo behavior that strengthens the potential of NLC to treat the disease
of the posterior segment of the eye.

Conclusion:

These NLC-based systems have proven to be a promising alternative in place of invasive
intravitreal injections with improved patient compliance.
Green Synthetic Strategies and Pharmaceutical Applications of Thiazine and its Derivatives: An Updated Review
Authors: Ratan Yashumati , Rajput Aishwarya , Pareek Ashutosh , Jain Vivek , Pareek Aaushi , Gupta Madan Mohan , Kamal Mohammad Amjad
Published: September 2023

Thiazines are a sizable class of organic heterocycles that are notable for their skeletal
versatility and relative chemical simplicity, making them among the most flexible sources of biologically
active compounds. The term "green synthesis" refers to implementing energy-efficient
procedures for the nature-friendly production of materials and chemicals using green solvents,
catalysts, and suitable reaction conditions. Considering the importance of green chemistry and the
outstanding therapeutic profile of thiazines, the present work was designed to review the recent
advances in green chemistry-based synthetic strategies of thiazine and its derivatives. The green
synthetic approaches, including microwave-assisted, ultrasound-assisted, and various other synthetic
methods for thiazine and its derivatives, were discussed and generalized. In addition, applications
of thiazine and its derivatives in pharmaceutical sciences were explained with examples of
marketed drugs.The discussed sustainable synthetic methods for thiazines and their derivatives
could be useful in developing other medicinally important lead molecules. They could also aid in
developing new synthetic schemes and apparatuses that may simplify chemical manufacturing
processes and enable novel reactions with minimal by-products while questing for optimal, green
solvents. This review can help anyone interested in this fascinating class of heterocycles to make
decisions about selecting targets and tasks for future research.
Neuropsychiatric Symptoms and Trajectories of Dependence and Cognition
in a Sample of Community-dwelling Older Adults with Dementia
Authors: Kociolek Anton J. , Fernandez Kayri K. , Hernandez Michelle , Jin Zhezhen , Cosentino Stephanie , Zhu Carolyn W. , Gu Yian , Devanand Davangere P. , Stern Yaakov
Published: September 2023

Background and Objectives:

Neuropsychiatric symptoms (NPS), including psychotic symptoms (hallucinations, illusions, delusions), agitation/aggression, and depressed mood, are common in individuals with Alzheimer’s disease (AD) and predict poorer outcomes, including faster disease progression. We aimed to evaluate associations between NPS and cognition and dependence in a multi-ethnic sample of community-dwelling older adults with AD.

Methods:

Predictors 3 (P3) is a cohort study of AD disease courses recruiting older adults aged 65 and above residing in upper Manhattan. A total of 138 of 293 participants had probable AD at the study baseline. We fit linear mixed models to examine longitudinal associations of time-varying NPS (psychotic symptoms, agitation/aggression, and depressed mood) with dependence and cognition, adjusted for race-ethnicity, sex, education, age, clinical dementia rating score, APOE-ϵ4, and comorbidity burden; separate interaction models were fit for age, Hispanic ethnicity, and sex.

Results:

Psychotic symptoms were associated with faster rates of increasing dependence and declining cognition over time, agitation/aggression with faster rates of declining cognition, and depressed mood with faster rates of increasing dependence. Among psychotic symptoms, delusions, but not hallucinations or illusions, were associated with worse outcome trajectories. Depressed mood predicted an accelerated increase in dependence in males but not females.

Conclusion:

Our results confirm and extend prior results in clinic-based samples. The presence of NPS was associated with worse trajectories of dependence and cognition in this muti-ethnic sample of older adults with AD. Importantly, sex modified the association between depressed mood and dependence. Our results on NPS as predictors of differential AD progression in a community-dwelling, ethnically diverse sample serve to better inform the clinical care of patients and the future development of AD therapies
Withdrawn: Natural Existence and Bioactivity of Flavonoids: Synthetic Strategies and Mechanistic Pathways
Authors: Sharma Shivangi , Mishra Pankaj Kumar , Singh Shivendra
Published: September 2023

Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been
withdrawn.

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Synthetic Approaches and Reactions of 2-(Arylidene)benzo[b]thiophen- 3(2H)one-1,1-dioxides
Authors: Barick Subrata , Kumar Manvendra , Kumar Raj
Published: September 2023

2-(Arylidene)benzo[b]thiophen-3(2H)one 1,1-dioxides are oxidized form of thioaurones.
Various methods have been reported for their synthesis, e.g., a) condensation of benzo[b]thiophen-
3(2H)one 1,1-dioxides with aryl aldehydes under acidic or basic conditions, b) oxidation of thioaurones
with hydrogen peroxide or sodium perborate tetrahydrate, c) from the catalytic reaction of iodonium
ylides with (bis(trifluoroacetoxy)iodo) benzene in presence copper(II)acetoacetonate, d)by
ring contraction of 1-thioflavones in the presence of ceric ammonium nitrate. The reports have shown
addition reactions with p-thiocresol in the absence of any catalyst, conjugated addition product without
hetero ring opening with Grignard reagent, forms corresponding oxime and hydrazone with hydroxyl
amine and phenyl hydrazine, respectively, produces polycyclic compounds with enamines, shows contrasting
behavior with NBS and gives addition products with organophosphorus compounds in both
hydroxylic and non-hydroxylic solvents which depends on reaction medium. In the present minireview,
we have discussed the various synthetic strategies and reactions of 2-
(arylidene)benzo[b]thiophen-3(2H)one 1,1-dioxides, along with their reported utilities.
An Exploration of Some Predictors of Quality of Life-Related to the Innate
Immune System, Inflammation, and Disease Activity in Patients with
Behcet's Syndrome: An Analytical Cross-sectional Study
Authors: Faghfouri Amir Hossein , Shoura Seyyed Morteza Seyyed , Papi Shahab , Khabbazi Alireza , Baradaran Behzad , Badpeyma Mohaddeseh , Faghfuri Elnaz
Published: September 2023

Background:

Behçet's disease (BD) has a growing prevalence in Silk Road countries. The aim of our cross-sectional study was to explore the clinical and molecular predictors of quality of life in BD patients.

Material and Methods:

One hundred and fifty consecutive Iranian BD patients with an age range between 20-50 years were included. The Leeds Behçet's disease quality of life (BDQoL) in Persian form was fulfilled to evaluate the quality of life. Anthropometric measurements were carried out us-ing the calibrated scales. Iranian Behcet's Disease Dynamic Activity Measure (IBDDAM), Behcet's disease current activity form (BDCAF), and Total Inflammatory Activity Index (TIAI) were used to assess BD activity. mRNA expression of toll-like receptors 2 and 4 (TLR2 and TLR4) and tumor-necrosis-factor-alpha (TNF-α) levels in serum were measured by real-time polymerase chain reac-tion (PCR) and ELISA, respectively. Multiple linear backward regression at P = 0.1 was used to study the potential predictors of quality of life.

Results:

TLR2 and BDCAF were shown to be the most important predictors of quality of life in BD patients by 22%. There were positive associations between them (β = 0.326, p = 0.013 for BDCAF; β = 0.366, p = 0.006 for TLR2) and BDQoL value.

Conclusion:

Higher TLR2 expression as a key protein in recognizing pathogens by innate immunity and BDCAF value as a comprehensive BD assessing scale contribute to poor quality of life among BD patients. Emphasizing therapeutically, approaches associated with lower TLR2 expression and BDCAF value can be considered in future studies.
The Pharmacological Potential of Resveratrol in Reducing Soft Tissue
Damage in Osteoarthritis Patients
Authors: Singh Kuldeep , Gupta Jeetendra Kumar , Kumar Shivendra
Published: September 2023

Osteoarthritis is a degenerative joint disease that causes the cartilage and bone underneath
the joint to break down. This causes pain and stiffness. Resveratrol, a polyphenolic compound
found in various vegetables, fruits, and red wine, has been studied for its beneficial effects
on osteoarthritis. Resveratrol has been shown to target a variety of pathways, including the NF-κB,
PI3K/Akt, MAPK/ERK, and AMPK pathways. In particular, resveratrol has been studied for its potential
use in treating osteoarthritis, and it has been shown to reduce inflammation, reduce cartilage
degradation, and improve joint function. In this review, we discuss the evidence for the pharmacological
use of resveratrol in minimizing soft tissue damage associated with osteoarthritis. We summarize
the studies on how resveratrol has anti-inflammatory, anti-oxidant, and anti-apoptotic effects,
as well as effects on cartilage degradation, osteoblast and synoviocyte proliferation, and cytokine
production. We also discuss the possible mechanisms of action of resveratrol in osteoarthritis
and its potential as a therapeutic agent. Finally, we discuss the potential risks and adverse effects
of long-term resveratrol supplementation. Overall, resveratrol has been found to be a possible
treatment for osteoarthritis because of its anti-inflammatory, anti-oxidant, and anti-apoptotic properties,
and its ability to control the production of enzymes that break down cartilage, osteoblasts, and
synoviocytes. Although numerous clinical studies have demonstrated resveratrol's efficacy as an osteoarthritis
management agent, further long-term studies are needed to better understand the safety
and potential benefits of using resveratrol for osteoarthritis management.
GastroNet: A Custom Deep Learning Approach for Classification of Anomalies
in Gastrointestinal Endoscopy Images
Authors: Mary.  A. Anitha , Raj  A. Peniel Winifred , Karthik C. , Karunaharan Aldrin
Published: September 2023

Introduction:

Among all cancer forms, gastrointestinal (GI) cancer is the most serious condition that spreads quickly and requires early detection. GI disorders claim the lives of up to nearly two million people worldwide. To lower the mortality rate from GI cancer, early detection is essential.

Methods:

For the identification of GI illnesses, such as polyps, stomach ulcers, and bleeding, endoscopy is the gold standard in the medical imaging industry. The numerous images produced by endoscopy require an enormous amount of time for the specialist to diagnose the disease. It makes manual diagnosis difficult and has sparked research on automatic computer-based approaches to diagnose all the generated images quickly and accurately. AI-based algorithms have already been used in endoscopy images with promising outcomes and have enhanced disease identification and classification with precision. However, there are still a lot of issues to be solved, including figuring out potential biases in algorithms and improving interpretability and generalizability.

Results:

The proposed GastroNet model creates a system for classifying digestive problems for the Kvasir Version 1 dataset. The framework consists of different CNN layers with multiple filters, and average max-pooling is used to extract image features. The optimization of network parameters is done using the Stochastic Gradient Descent (SGD) algorithm.

Conclusion:

Finally, the robustness of the proposed model is compared with other state-of-the-art models like VGG 19, ResNet 50, Inception, and Xception in terms of evaluation metrics.
A Comparison of Colour Doppler Ultrasound and 2D Ultrasound as Promising
Prediction Methods for the Treatment effect of Patients with Advanced Cervical
Cancer
Authors: Dai Beibei
Published: September 2023

Background:

A number of studies have evaluated the effect of colour Doppler ultrasound in patients with cervical cancer.

Objective:

This study aims to evaluate the efficacy of colour Doppler ultrasound and two-dimensional ultrasound of monitoring patients with cervical cancer.

Methods:

Colour Doppler ultrasound (Experimental group) and two-dimensional ultrasound (Control group) are used to monitor cervical cancer and assess the treatment effects. PFS, CI, HR, DCR, ORR, PR, SD, PD, ROD, sensitivity, and specificity, accuracy between the two groups were collected and analyzed.

Results:

A total of 50 patients are included in this study, and the results show that PFS (Experimental group (EG) 5.8±2.2 versus Control group (CG) 6.1±2.6), CI (EG 20% versus CG 16%), HR (EG0.31±0.18 versus CG 0.36±0.21), DCR (EG 80% versus CG 84%), ORR(EG 28% versus CG 36%), PR (EG 16% versus CG 20%), SD (EG 48% versus CG 56%), PD (EG 12% versus CG 16%) (EG 12% versus CG 16%), ROD(EG 44% versus CG 52%) between the two groups are >0.05, and the values of sensitivity (EG 75.6% versus CG 40.2%), specificity (EG 78.4% versus CG 43.3%), and accuracy(EG 80.5% versus CG 41.4%) between the two groups are<0.05.

Conclusion:

Both Colour Doppler ultrasound and two-dimensional ultrasound are effective methods to evaluate the efficacy of concurrent chemo-radiotherapy in patients with cervical cancer.
TIPS with a Twist � The Real Life Management of a Case of Budd-Chiarirelated
Acute Liver and Subsequent Multiple Organ Failure
Authors: Craciun Rares , Chira Romeo , Nemes Andrada , Stefanescu Horia , Cocu Simona , Procopet Bogdan
Published: September 2023

Introduction:

Budd-Chari syndrome (BCS) is a rare condition defined by the obstruction of hepatic venous outflow. BCS is a relatively infrequent cause of acute liver failure (ALF), accounting for less than 1% of cases. Treatment for acute BCS consists of a stepwise approach, requiring anticoagulation, angioplasty, transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation.

Case Report:

We present the case of a 31-year-old female patient with BCS, which led to ALF and subsequent multiple organ failure, which was successfully treated with TIPS and endovascular coil placement. Initial diagnostic workup revealed the complete obstruction of the hepatic venous outflow, spleno-mesenteric confluent thrombosis, and biochemical criteria of ALF. Her condition rapidly deteriorated towards multiple organ failure. At one point, the MELD score was 42, while the SOFA score predicted a mortality rate of >95%. Following continuous venovenous hemodiafiltration with cytokine adsorbent filters, TIPS was inserted, resulting in a portal pressure gradient (PPG) of 14 mmHg. Following TIPS, the patient had persistent ascites and later presented an episode of gastric variceal bleeding with endoscopic and surgical treatment failure. TIPS revision with further dilation led to a final PPG of 6 mmHg. During the procedure, selective embolization by coil placement of the spleno-gastric collateral circulation ultimately resolved the variceal bleeding. In the aftermath, the patient had complete organ failure remission and was successfully discharged with no ascites, encephalopathy, or significant impairment regarding daily life activities.

Conclusion:

In the rare setting of BCS complicated with ALF and portal hypertension-related complications, TIPS and endovascular embolization provide a unique, effective, and against-all-odd solution.