bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgery versus Carboplatin and Cisplatin followed by Radiotherapies and Surgery in Locally advanced Gastrointestinal tract Cancer
Authors: Ye Xuxing , Wu Zhangqiang , Teng Weijun , Zhang Yili , Chen Yanping , Sheng Lin , Lin Junmei , Wang Xiaobo 
Published: November 2024

Abstract

Background: Gastrointestinal tract cancer is still prevalent in the world. Localized GI cancer treatment has greatly relied on surgery, even for locally advanced diseases. Aim and objectives: The goal of this study was to assess the prognosis of direct surgery and neoadjuvant chemoradiotherapy and surgery in patients with locally advanced GI tract cancers.
Materials and Methods: A cross-sectional study was done on patients diagnosed with locally advanced GI cancers who were treated at Zhejiang Jinhua Guangfu Cancer Hospital between the period Jan 2021 to December 2023, total number of patients was 245. Patients were divided into two cohorts: DS of 107 and CRS of 138. Disease-free survival was the main predictor, while the others were considered secondary endpoints; these were overall survival, pathological complete response rate, postoperative complications, and R0 resection rate.
Results: Disease-specific survival benefitted the CRS cohort relative to the DS cohort with a 2-year DFS of 76.81% compared to 65.42% (p= 0. 049). Median DFS also favored the CRS group (34. 7 months vs 28. 3 months, p = 0. 023). While not statistically significant, there was a trend towards improved OS in the CRS cohort (2-year OS rate: The results are as follows: 81. 16% versus 72. 90%, p=0.124. The CRS group had higher resection of R0 (92.8% vs 86.0%, p=0.082), and similarly, the local recurrence and distant metastases, although non-significant, were lower in this group.
Conclusion: Locally advanced GI tract cancer appears to be improved from neoadjuvant-applied chemoradiotherapy followed by surgery rather than upfront surgery. Whereas, the trend about OS was in favor of the CRS approach, perhaps more time is required to observe these differences. The multimodal technique had reasonable presurgical toxicities and did not worsen the rate of postoperative complications. These findings support the consideration of neoadjuvant chemoradiotherapy can be recommended as a viable treatment approach for locally advanced GI tract cancers but future comparative prospective trials must be conducted to determine long-term survivals and quality of life patterns.
Physiological responses and gene expression of Gracilaria chilensis under infection of the green epiphyte Ulva sp
Authors: SOLANA SARA USANDIZAGA , Beltrán Jessica , Vargas Jaime , Figueroa Álvaro , Faugeron Sylvain , Guillemin Marie-Laure , Camus Carolina 
Published: November 2024

Abstract

Ulva sp. infection in seaweed is considered one of the most harmful infections, since it penetrates deep into the host cell wall and disorganizes the cortical tissue. In Gracilaria chilensis farms, epiphytism is one of the major biological problems and strong fluctuations in this rhodophyta landings have been documented in the past decades. The present study evaluated the damage of Ulva sp. infection through histological assessment, germination of the epiphytic algal spores on G. chilensis, the photosynthetic response and gene expression associated with stress after exposure to epiphyte infection. The histological results showed a significant and a characteristic damage according to the type of infection described by this species. In addition, a higher infection in farmed than in natural individuals was observed, along with increased photoinhibition of the maximum fluorescence quantum yield (Fv/Fm). Two genes, one related to photosynthesis (PSBO) and the other responsible for neutralizing free superoxide radicals (SOD-C), followed the same pattern. VBPO, a gene related to the halo-organic compounds synthesis, showed a higher expression in infected thalli, independent of the population type, suggesting a higher protection of the alga from oxidative damage. This study confirms the sensibility of farmed populations of G. chilensis to infection by Ulva sp. and the existence of an active response to early infection.
A Covalent Chemical Probe for Chikungunya nsP2 Cysteine Protease with Antialphaviral Activity and Proteome-wide Selectivity
Authors: Willson Timothy , Ghoshal Anirban , Tse Edwin , Hossain Mohammad Anwar , Asressu Kesatebrhan Haile , Merten Eric , Sears John , Howell Stefanie , Perveen Sumers , Burdick Jane , Morales Noah , Martinez Sabian , Law Isabella , Bennett Davenport , Morrison Thomas , Strebblow Zachary , Streblow Daniel , Mordant Angie , Webb Thomas , Cabrera Aurora , Herring Laura , Arrowsmith Cheryl , Pearce Kenneth , Moorman Nathaniel , Heise Mark , Couñago Rafael Miguez , Brown Peter 
Published: November 2024

Abstract

RA-0003022 (3) was identified as a high-quality covalent chemical probe for Chikungunya nsP2 cysteine protease (nsP2pro). Isoxazole 3 covalently captured the active site C478 and inactivated the enzyme with kinact/Ki ratio of 6000 M–1s–1. A negative control analog RA-0025453 (4) retained the covalent warhead but demonstrated >100-fold decrease in enzyme inhibition. Isoxazoles 3 and 4 were stable cross a wide range of pH in solution and upon prolonged storage as solids. The covalent chemical probe 3 was inactive across a panel of 23 human and viral cysteine proteases and demonstrated remarkable proteome-wide selectivity by two chemoproteomic methods. Isoxazole 3 reduced viral titer against infectious isolates of Chikungunya, Mayaro, and Venezuelan Equine Encephalitis viruses demonstrating its activity on both New and Old World alphaviruses. Isoxazole 3 and its negative control 4 will find utility as covalent chemical probes to study the role of the nsP2pro in alphaviral replication and virulence.
The Impact of the Intensity and Changes in Persistent Social Isolation among Middle and Older Adults on Frailty
Authors: Kim Min-Soo , Kim Hyun-Joo , Kim Jang Mook 
Published: November 2024

Abstract

Objective
The dynamic nature of mental health, such as social isolation, is constantly changing and can negatively impact frailty, including the physical and mental health of middle-aged and older. The objective of this study was to examine the effects of the intensity and changes in continuous social isolation on frailty in the middle-aged and older population, while identifying vulnerable groups based on individual characteristics.
Methods
This study was conducted using data from the Korean Longitudinal Study of Aging (KLoSA) from 2006 to 2022. The study included 5,349 middle-aged and older people aged 45 or older. Group-based trajectory modeling (GBTM) and generalized estimating equations (GEE) were applied to observe the impact of the intensity and change of persistent social isolation on frailty. In addition, subgroup analyses were conducted, taking gender and age into account.
Results
The GBTM analysis identified seven social isolation trajectories: Sustained Not SI (14.8%), Changed Mild to Severe SI (4.3%), Changed Not to Mild SI (14.1%), Sustained Mild SI (37.1%), Sustained Moderate SI (11.4%), Sustained Severe SI (6.8%), and Changed Mild to Not SI (11.4%). In terms of the intensity of social isolation, compared to the Sustained Not SI group, the frailty index was significantly higher in the Sustained Severe SI group (β: 0.053, SE: 0.007, 95% CI: 0.040-0.067, P-value <0.001). In terms of changes in social isolation, the frailty index was higher in the Changed Mild to Severe SI group (β: 0.039, SE: 0.007, 95% CI: 0.026-0.053, P-value <0.001). This tendency was more pronounced in female and aged 65 + in the subgroup analyses by gender and age.
Conclusion
In the middle-aged and older age groups, the risk of frailty may increase when experiencing continuous social isolation intensity and changes. This effect was particularly high in female and in the older age group. Therefore, it is important to develop social activity support policies for early intervention and customized health management by considering various factors such as gender and age.
Prediction of SafD adhesin strong binding peptides for pilus proteins assembly suppression in the prevention of Salmonella-induced biofilm formation using virtual mutagenesis studies
Authors: Samanta Priyanka , Ghorai Sourav 
Published: November 2024

Abstract

Clinical isolates of Salmonella enterica contain Saf pili that establish initial bacterial attachment with the human epithelium to form biofilms which are a common cause of several abdominal complications. Due to the rise in antibiotic-resistant strains of bacteria, an alternate strategy of inhibiting the initial bacterial contact with the epithelial layers is well-studied. Saf pili undergo a chaperone-usher pathway assembly mechanism to generate its host-recognizing functional form, SafDAA. Preventing the biogenesis of the pili by targeting the SafD and SafA proteins polymerization will prevent host recognition. In this study, virtual mutagenesis studies using the recently reported X-ray crystal structure of an N-terminal peptide co-crystallized with SafD led to the design of peptides that exhibit enhanced binding with SafD compared to its native peptide. Virtual alanine mutagenesis and protein–peptide interaction studies identified several hotspot residues. Molecular dynamics simulations and binding free energy calculations identified key pairwise interactions between the designed peptides and SafD. In addition, a library of 110 peptides that are predicted to bind strongly with SafD is prepared which can serve as an excellent resource for the discovery of novel SafD-binding peptides. This work provided new insights into the design of novel anti-virulence therapies targeting Salmonella enterica.
Phytochemical analysis, cytotoxicity, anti-trypanosomal, anti-oxidant and anti-inflammatory activities of Clausena anisata fruit, Azadirachta indica leaf and stem bark extracts
Authors: Kumatia Emmanuel Kofi , Zoiku Felix Kwame , Baffour Kyei , Anokye-Kumatia Anne Boakyewaa , Asase Alex 
Published: November 2024

Abstract

Human African Trypanosomiasis (HAT) is an infectious disease which kills humans and animals as a result of hematological distortions, oxidative stress, tissue and neuro inflammations. This study reports on the difference in cytotoxicity, anti-trypanosomal, anti-oxidant and anti-inflammatory activities of ethanol extracts from Clausena anisata (CFE), Azadirachta indica (Neem) leaf (NLE) and stem bark (NSBE), medicinal plants used to treat HAT in endemic communities. The extracts remarkably inhibited Trypanosomal brucei brucei (Gutat 3.1) parasite in vitro with CFE recording the highest effect with IC50 of 0.0055 (0.0955) µg/mL The IC50 of the standard Coptis japonicum, was 0.5957 (0.0693) µg/mL. Also, the anti-trypanosomal activity of NLE was 123.34% higher than that of NSBE. Percentage number of wells containing viable T. b. brucei parasites were very significantly (P < 0.001) reduced for all the extracts after 48 h of incubation. Furthermore, the extracts did not show cytotoxicity against the liver (HepG2) cells (CC50s > 100 µg/mL and SI = 13.12–32,025.45). NSBE contained the highest quantity of phenolic compounds and flavonoids and also produced the highest anti-oxidant and anti-inflammatory activity in the DPPH free radical scavenging assay (IC50 = 4.99 ± 0.018) and protein denaturation assay (IC50 = 0.1805 ± 0.0002 µg/mL). In addition, phytochemical analysis showed that NLE contained the highest number of classes of phytochemical constituents (7) among the extracts. These results indicates that CFE, NLE and NSBE possessed significant anti-trypanosomal activity as a result of their anti-oxidant and anti-inflammatory actions. However, a different mechanism was also involved in the anti-trypanosomal activity of CFE and NLE, since their anti-trypanosomal activity is greater than NSBE which demonstrated the highest anti-oxidant and anti-inflammatory activities. Due to the remarkable anti-trypanosomal action of CFE, its constituents are being isolated for possible development into novel anti-trypanosomal agents.
Airflow characteristics of the stepped dropshaft in the deep tunnel storage system
Authors: Sun Jingkang , Fei Zhaodan , Qian Shangtuo , Feng Jiangang , Xu Hui , Liu Jiachun , Zhang Rui 
Published: November 2024

ABSTRACT

The deep tunnel storage system, mainly consisting of underground tunnels and dropshafts, is effective for dealing with urban waterlogging. A stepped dropshaft is suitable for the system to safely transport water to underground tunnels and efficiently release air carried by water. In this study, the air inflow discharge, air vent discharge, and air discharge into underground tunnels are investigated experimentally. As the dimensionless water flow discharge increases to 0.56, the water flow successively forms the nappe flow, transition flow, and skimming flow regimes, the relative air inflow discharge decreases from 0.97 to 0.32, the relative air vent discharge decreases from 0.85 to 0.22, and the relative air discharge into underground tunnels fluctuates below 0.20. The exhaust capacity (the ratio of air vent discharge to air inflow discharge) reaches a maximum of 0.87 at the threshold between the nappe flow and the transition flow. Influences of flow discharge, step height, step rotation angle, outlet diameter of central exhaust pipe, and underground tunnel blockage on airflow characteristics are revealed. The prediction formulas for air inflow discharge, air vent discharge, and exhaust capacity are obtained with accuracies over 80%, providing a guide to the practical design and operation of stepped dropshafts.
Screening of Herbs with Potential Modulation of NLRP3 Inflammasomes for Acute Liver Failure: A Study Based on the Herb-Compound-Target Network and the ssGSEA Algorithm
Authors: Ou Haiya , Qiu Susu , Ye Xiaopeng , Wang Xiaotong 
Published: November 2024

Objective:
NLRP3 inflammasomes are considered to be key factors in the pathogenesis
of Acute Liver Failure (ALF). Some NLRP3 inflammasomes are considered to be key factors in the pathogenesis of Acute Liver Failure (ALF). Some Traditional Chinese Medicines (TCMs) have shown protec-tive and therapeutic effects against ALF by inhibiting NLRP3 inflammasomes. However, the in-hibitory effects of most TCMs on ALF remain to be further elucidated. This study aimed to screen potential herbs that can treat ALF based on the inhibition of NLRP3 inflammasomes.

Methods:
Initially, we constructed the target set for 502 herbs. Subsequently, based on the target set and the gene set related to the NLRP3 inflammasome, using the ssGSEA algorithm, we evaluated herb scores and NLRP3 scores in the ALF expression matrix and performed a preliminary herb screening based on score correlations. Through bioinformatics approaches, we identified the key targets for candidate herbs and determined core herbs based on the herb-compound-target network. Furthermore, molecular docking and molecular biology methods validated the screening results of the herbs.

Results:
A total of 18 crucial targets associated with the inhibition of the NLRP3 inflammasome were identified, which included ALDH2, HMOX1, and VEGFA. Subsequently, based on these key targets, a set of 10 primary herbs was chosen, notably Qinghao, Duzhong, and Gouteng. Moreover, the results were verified through molecular docking and molecular dynamic simulation.

Conclusion:
Ten key herbs have been identified as potential inhibitors of the NLRP3 inflammasome, offering insights into ALF therapy for drug development.
The Effects of Resveratrol in a Randomized Clinical Trial on Drug-Induced Hyperlipidemia and Psychiatric Factors in People Living with HIV
Authors: Ahmadi-Mousavi Bahar , Karami-Mohajeri Somayyeh , Dabaghzadeh Fatemeh , Soltani Motahareh , Oghabian Zohreh , Sharifi Hamid 
Published: November 2024

Introduction:
People living with HIV (PLHIV) suffer from a range of consequences
related to infection, including hyperlipidemia and neurologic and sleep disorders. Supplements
containing phenolic compounds with high antioxidant properties can reduce these side effects.
Resveratrol is a phenolic compound that improves the symptoms of diabetes, cancer, and viral
infections. This study aimed to evaluate the effects of resveratrol on hyperlipidemia and neurological
problems in PLHIV in Iran.

Method:
In this double-blind, randomized clinical trial, 41 PLHIV were randomly assigned to
two groups: a placebo group (n=21) and a resveratrol group (n=20). Triglyceride and cholesterol
levels were determined for all the subjects before and one month after they used the medication.
Additionally, standard questionnaires were used to evaluate the quality of sleep, stress,
depression, and quality of life of the participants. The data were analyzed via analysis of covariance
in Stata 17.0.

Results:
The study population did not significantly differ in terms of age (p=0.49), sex
(p=0.09), marital status (p=0.90), level of education (p=0.90), duration of HIV infection
(p=0.54), or mode of HIV transmission (p=0.51). The administration of resveratrol did not
affect psychological parameters or blood cholesterol (p=0.091) or triglyceride (p=0.932) levels.

Conclusion:
The administration of resveratrol did not affect cholesterol or triglyceride levels
or the rates of depression, anxiety, sleep quality, or quality of life in PLHIV. The resveratrol
supplementation in a large-scale clinical study involving more patients for a longer course of
treatment may have had more significant effects on the serum levels of lipids and psychological
factors.

result:
The study population did not have significant age differences (p=0.49), gender (p=0.09), marital status (p=0.90), level of education (p=0.90), duration of HIV infection (p=0.54), and mode of HIV transmission (p=0.51). Administration of resveratrol did not affect psychological parameters and blood cholesterol (p=0.091) and triglycerides (p=0.932) levels.
Efficient Formylation of Alcohols Using a Core-Shell Magnetic Nanocomposite via Vilsmeier-Haack Complex Formation
Authors: Ebrahimzadeh Farzaneh 
Published: November 2024

Introduction:
The protection of the hydroxyl group as formamides is a crucial initial step in pharmaceutical synthesis.

Methods:
In this study, we investigated the O-formylation of alcohols using dimethylfor-mamide (DMF) in a mixture with a new magnetic nanocomposite Fe3O4@Chitosan/POCl2-x.

Results:
The results demonstrate that this core-shell heterogeneous nanocomposite facili-tates the formation of alkylformate, yielding products with high efficiency ranging from 79% to 96% within a remarkably short reaction time of 1 to 12 hours at room temperature, depending on the substrate structure. Significantly, the presence of this nanocomposite ex-hibits remarkable selectivity, favoring the formylation of less hindered benzylic and ali-phatic primary alcohols. However, bulkier alcohols and phenols exhibit lower reactivity under these conditions and thiols do not react. The simplicity of the work-up procedure, combined with the magnetic recyclability, makes it reusable and environmentally friendly.

Conclusion:
This study highlights the efficacy of this novel magnetic nanocomposite in facilitating formylation reactions, emphasizing its potential for application in pharmaceu-tical synthesis and bio compounds. This is due to its attributes of non-toxic nature, stabil-ity, and significant advantages over conventional methodologies.
Carboxylic Acids as Activators of NRF2: Antioxidant and Antiinflammatory Effects
Authors: Egbujor Melford Chuka 
Published: November 2024

Abstract:
The complex interaction between carboxylic acids and molecular signaling pathways,
particularly the nuclear factor erythroid 2-related factor 2 (NRF2) pathway, is of growing interest in
medicinal chemistry due to its potential therapeutic benefits. Carboxylic acids, which are widely
distributed in nature, are versatile regulators of cellular responses due to their ability to interact
with multiple signaling pathways, especially those involved in combating oxidative stress and inflammation.
Several carboxylic acids exhibit significant antioxidant and anti-inflammatory activities.
They have been identified as potential activators of the NRF2 transcription factor, a key regulator
of endogenous antioxidants that maintains cellular redox homeostasis and modulates the production
of several antioxidant proteins and detoxifying enzymes. The potential effects of carboxylic
acid-NRF2 crosstalk are exhibited in a variety of physiological processes, such as attenuation of
oxidative stress and inflammation, detoxification of xenobiotics, and modulation of the immune
system. The molecular docking of some carboxylic acids with NRF2 protein showed that their
binding affinities were comparable to dimethyl fumarate, a reference drug. The current review explores
the evolving landscape of carboxylic acid-NRF2 interactions and their mechanisms of action,
highlighting the possible impact of their antioxidant and anti-inflammatory effects on inflammation
and oxidative stress-mediated diseases. The natural and synthetic sources of NRF2-activating carboxylic
acids and the role of their chemical and physical properties in influencing NRF2-inducing
activities were discussed. Their potential challenges as future drugs and clinical trial prospects were
also highlighted. Carboxylic acid-NRF2 interactions offer potential for developing therapies that
will attenuate oxidative stress and inflammation.
Advancement of Artificial Intelligence in Drug Discovery: A Comprehensive Review
Authors: Mukherjee Debanjan , Sharma Tarun , Lunawat Akshay Kumar , Awasthi Ankit , Kurmi Balak Das , Kumar Manish , Gupta Ghanshyam Das , Thakur Shubham 
Published: November 2024

Abstract:
The traditional drug discovery process is notoriously time-consuming, expensive, and
damaged, with high failure rates. However, the recent surge in Artificial Intelligence (AI) has presented
itself as a game-changer in this field. This comprehensive review delves into the profound
impact of AI on various aspects of drug discovery, encompassing crucial stages like target identification,
molecular analysis, compound screening, and even drug development. Machine learning algorithms
are pivotal in analyzing vast datasets to predict important aspects of potential drug candidates.
These predictions include their pharmacokinetic properties (how the body absorbs and eliminates
them) and possible toxicity, effectively streamlining the process and reducing risks associated with
further development. Additionally, AI facilitates the exploration of vast chemical spaces, enabling
the design and synthesis of novel drug candidates with enhanced efficacy and specificity. The review
highlights AI's transformative potential in drug discovery and acknowledges the existing challenges.
Concerns surrounding data quality, interpretability of AI models, and ethical considerations are addressed,
paving the way for responsible development and integration of AI within the pharmaceutical
industry. Ultimately, this review underscores AI's massive potential in revolutionizing drug discovery,
offering a path towards faster development of life-saving treatments and fostering healthcare
advancements.