bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the multi-dimensional resilience of water distribution networks to contamination events
Authors: Acharya Albira , Liu Jia , Shin Sangmin 
Published: February 2023

Abstract
Recent contamination events in water distribution networks (WDNs) suggest the need for resilience strategies to address the uncertainty of contamination intrusion. Resilience-based decision-making requires a resilience evaluation process. However, the suggestions on resilience options can vary with the definition of the system's functionality considered in the resilience evaluation. Thus, this study characterized resilience and its attributes (i.e., robustness, loss rate, recovery rate, failure duration, and recovery completeness) in multiple functional dimensions for a WDN to contamination events. The resilience evaluation was performed using a resilience measure based on a time-dependent functionality variation during contamination events. This study considered the functionalities in four dimensions: the contaminated node, compromised demand, biodegradable dissolved organic carbon concentration, and consumed mass. The hydraulic and water quality models were simulated using EPANET-MSX to evaluate the functionality variation under bacterial intrusion events. The results noted that the resilience levels significantly varied with the functional dimensions and relatedness and contamination event conditions. The results also identified that different profiles of resilience attributes could characterize similar levels of multi-dimensional resilience. The findings suggest insights on incorporating the concept of multi-dimensional resilience in decision-making processes, therefore achieving the goal of improving the overall resilience of the system in diverse aspects of functionality.
Nanodiamond Mediated Molecular Targeting in Pancreatic Ductal Adenocarcinoma:
Disrupting the Tumor-stromal Cross-talk, Next Hope on the
Horizon?
Authors: Singh Mohini , Pal Paulami , Dutta Rajat Subhra , Marbaniang Daphisha , Ray Subhabrata , Mazumder Bhaskar 
Published: February 2023

Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is one of the foremost causes of cancer-related
morbidities worldwide. Novel nanotechnology-backed drug delivery stratagems, including molecular
targeting of the chemotherapeutic payload, have been considered. However, no quantum leap in the
gross survival rate of patients with PDAC has been realized. One of the predominant causes behind this
is tumor desmoplasia, a dense and heterogenous stromal extracellular matrix of the tumor, aptly termed
tumor microenvironment (TME). It plays a pivotal role in the tumor pathogenesis of PDAC as it occupies
most of the tumor mass, making PDAC one of the most stromal-rich cancers. The complex crosstalk
between the tumor and dynamic components of the TME impacts tumor progression and poses a
potential barrier to drug delivery. Understanding and deciphering the complex cascade of tumorstromal
interactions are the need of the hour so that we can develop neoteric nano-carriers to disrupt
the stroma and target the tumor. Nanodiamonds (NDs), due to their unique surface characteristics, have
emerged as a promising nano delivery system in various pre-clinical cancer models and have the potential
to deliver the chemotherapeutic payload by moving beyond the dynamic tumor-stromal barrier. It
can be the next revolution in nanoparticle-mediated pancreatic cancer targeting.
Bilateral Superficial Trigeminal Nerve Blocks are not More Effective
than a Placebo in Abolishing Post-operative Headache Pain in Pituitary
Transsphenoidal Neurosurgery: A Prospective, Randomized, Doubleblinded
Clinical Trial
Authors: Srejic Una , Litonius Erik , Gandhi Seema , Talke Pekka , Maties Oana , Siegmueller Claas , Magsaysay Avic , Hasen Daniel , Kunwar Sandeep , Seth Rahul , Gibson Lizbeth , Bickler Philip 
Published: February 2023

Background:
Pituitary neurosurgery executed via the transsphenoidal endonasal
approach is commonly performed for pituitary adenomas. Reasons for prolonged hospital stay
include postoperative headache and protracted nausea with or without vomiting. Bilateral
superficial trigeminal nerve blocks of the supra-orbital V1 and infra-orbital V2 (SION) nerves
performed intra-operatively as a regional anesthetic adjunct to general anesthesia were
hypothesized to decrease 6 hours postoperative morphine PCA (patient-controlled analgesia) use by
patients.

Methods:
Forty-nine patients, following induction of general anesthesia for their transsphenoidal
surgery, were prospectively randomized in a double-blinded fashion to receive additional regional
anesthesia as either a block (0.5% ropivacaine with epi 1:200,000) or placebo/sham (0.9% normal
saline). The primary endpoint of the study was systemic morphine PCA opioid consumption by the
two groups in the first 6-hours postoperatively. The secondary endpoints included (1) pain
exposure experienced postoperatively, (2) incidence of postoperative nausea and vomiting, and (3)
time to eligibility for PACU discharge.

Results:
Of the 49 patients that were enrolled, 3 patients were excluded due to protocol violations.
Ultimately, there was no statistically significant difference between morphine PCA use in the 6
hours postoperatively between the block and placebo/sham groups. There was, however, a slight
visual tendency in the block group for higher pain scores, morphine use p=0.046, and delayed
PACU discharge. False discovery rate corrected comparisons at each time point and then revealed
no statistically significant difference between the two groups. There were no differences between
the two groups for secondary endpoints.

Conclusion:
It was found that a 6-hour postoperative headache after endoscopic trans-sphenoidal
pituitary surgery likely has a more complicated mechanism involving more than the superficial
trigeminovascular system and perhaps is neuro-modulated by other brain nuclei.
Identification of Potential Biomarkers in Stomach Adenocarcinoma using
Machine Learning Approaches
Authors: Nazari Elham , Pourali Ghazaleh , Khazaei Majid , Asadnia Alireza , Dashtiahangar Mohammad , Mohit Reza , Maftooh Mina , Nassiri Mohammadreza , Hassanian Seyed Mahdi , Ghayour-Mobarhan Majid , Ferns Gordon A. , Shahidsales Soodabeh , Avan Amir 
Published: February 2023

Background:
Stomach adenocarcinoma (STAD) is a common cancer with poor clinical outcomes
globally. Due to a lack of early diagnostic markers of disease, the majority of patients are diagnosed
at an advanced stage.

Objective:
The aim of the present study is to provide some new insights into the available biomarkers
for patients with STAD using bioinformatics.

Methods:
RNA-Sequencing and other relevant data of patients with STAD from The Cancer Genome
Atlas (TCGA) database were evaluated to identify differentially expressed genes (DEGs). Then, Machine
Learning algorithms were undertaken to predict biomarkers. Additionally, Kaplan–Meier analysis
was used to detect prognostic biomarkers. Furthermore, the Gene Ontology and Reactome pathways,
protein-protein interactions (PPI), multiple sequence alignment, phylogenetic mapping, and correlation
between clinical parameters were evaluated.

Results:
The results showed 61 DEGs, and the key dysregulated genes associated with STAD are
MTHFD1L (Methylenetetrahydrofolate dehydrogenase 1-like), ZWILCH (Zwilch Kinetochore Protein),
RCC2 (Regulator of chromosome condensation 2), DPT (Dermatopontin), GCOM1 (GRINL1A complex
locus 1), and CLEC3B (C-Type Lectin Domain Family 3 Member B). Moreover, the survival analysis
reported ASPA (Aspartoacylase) as a prognostic marker.

Conclusion:
Our study provides a proof of concept of the potential value of ASPA as a prognostic factor
in STAD, requiring further functional investigations to explore the value of emerging markers.
Drug Design and Disease Diagnosis: The Potential of Deep Learning
Models in Biology
Authors: Sreeraman Sarojini , Kannan Mayuri P. , Singh Kushwah Raja Babu , Sundaram Vickram , Veluchamy Alaguraj , Thirunavukarasou Anand , Saravanan Konda Mani 
Published: February 2023

Abstract:
Early prediction and detection enable reduced transmission of human diseases and provide
healthcare professionals ample time to make subsequent diagnoses and treatment strategies. This, in
turn, aids in saving more lives and results in lower medical costs. Designing small chemical molecules
to treat fatal disorders is also urgently needed to address the high death rate of these diseases worldwide.
A recent analysis of published literature suggested that deep learning (DL) based models apply more
potential algorithms to hybrid databases of chemical data. Considering the above, we first discussed the
concept of DL architectures and their applications in drug development and diagnostics in this review.
Although DL-based approaches have applications in several fields, in the following sections of the article,
we focus on recent developments of DL-based techniques in biology, notably in structure prediction,
cancer drug development, COVID infection diagnostics, and drug repurposing strategies. Each
review section summarizes several cutting-edge, recently developed DL-based techniques. Additionally,
we introduced the approaches presented in our group, whose prediction accuracy is relatively comparable
with current computational models. We concluded the review by discussing the benefits and drawbacks
of DL techniques and outlining the future paths for data collecting and developing efficient computational
models.
Phytochemicals in the Synthetic Era: A Potential Oncosuppressor against Cancer
Stem Cells
Authors: Maru Devangkumar , Kumar Anmol 
Published: February 2023

Abstract:
CSCs (Cancer stem cells) are a subpopulation of transformed cells residing within the tumour that possesses
properties of stem cells, like self-renewal and differentiation. Different signalling pathways, epigenetic changes, and
interaction with a tumour microenvironment are found to be involved in the maintenance of stemness of CSCs and
contribute to chemoresistance. Hence, it is difficult to prevent and control progression completely without considering
CSCs as a crucial target. Some phytochemicals target different pathways and gene expression and modulate CSC
markers to suppress the stemness properties of cancer cells. Thus, phytochemicals potentially impact CSCs which may
be applied in chemo-prevention. This comprehensive review discusses some studied phytochemicals that suppress
stemness characters in various cancer types both in vitro and in vivo animal models. However, the chemo-prevention
ability of phytochemicals needs to be validated in further subsequent stages of clinical trials.
Novel 5-bromoindole-2-carboxylic Acid Derivatives as EGFR Inhibitors: Synthesis,
Docking Study, and Structure Activity Relationship
Authors: Hassan Omeed M. , Kubba Ammar , Tahtamouni Lubna H. 
Published: February 2023

Background:
The indole backbone is encountered in a class of N-heterocyclic compounds with physiological
and pharmacological effects such as anti-cancer, anti-diabetic, and anti-HIV. These compounds are becoming increasingly
popular in organic, medicinal, and pharmaceutical research. Nitrogen compounds' hydrogen bonding, dipole-
dipole interactions, hydrophobic effects, Van der Waals forces, and stacking interactions have increased their
relevance in pharmaceutical chemistry due to their improved solubility. Indole derivatives, such as carbothioamide,
oxadiazole, and triazole, have been reported to act as anti-cancer drugs due to their ability to disrupt the mitotic spindle
and prevent human cancer cell proliferation, expansion, and invasion.

Objectives:
To synthesize new 5-bromoindole-2-carboxylic acid derivatives that function as EGFR tyrosine kinase
inhibitors as deduced through molecular docking studies.

Methods:
Different derivatives of indole (carbothioamide, oxadiazole, tetrahydro pyridazine-3,6-dione, and triazole)
were synthesized and evaluated through different chemical, spectroscopic methods (IR, 1HNMR, 13CNMR, and MS)
and assessed in silico and in vitro for their antiproliferative activities against A549, HepG2, and MCF-7 cancer cell
lines.

Results:
According to molecular docking analyses, compounds 3a, 3b, 3f, and 7 exhibited the strongest EGFR tyrosine
kinase domain binding energies. In comparison to erlotinib, which displayed some hepatotoxicity, all of the evaluated
ligands displayed good in silico absorption levels, did not appear to be cytochrome P450 inhibitors, and were not hepatotoxic.
The new indole derivatives were found to decrease cell growth of three different types of human cancer cell lines
(HepG2, A549, and MCF-7), with compound 3a being the most powerful while still being cancer-specific. Cell cycle
arrest and the activation of apoptosis were the results of compound 3a's inhibition of EGFR tyrosine kinase activity.

Conclusion:
The novel indole derivatives, compound 3a in particular, are promising anti-cancer agents which inhibit
cell proliferation by inhibiting EGFR tyrosine kinase activity.
A New de novo Mosaic Mutation of PHEX Gene: A Case Report of a Boy
with Hypophosphatemic Rickets
Authors: Novizio Roberto , Terracciano Alessandra , De Bernardi Margherita Lucia , De Brasi Davide , Iolascon Achille , Monica Matteo Della , Scavuzzo Francesco , Serino Domenico , Novelli Antonio , Piscopo Carmelo 
Published: February 2023

Background:
X-linked hypophosphatemia is the most prevalent form of heritable rickets,
characterized by an X-linked dominant inheritance pattern. The genetic basis of X-linked hypophosphatemia
is a loss-of-function mutation in the PHEX gene (Phosphate regulating gene with
Homology to Endopeptidases on the X chromosome), which leads to an enhanced production of
phosphaturic hormone FGF23. X-linked hypophosphatemia causes rickets in children and osteomalacia
in adults. Clinical manifestations are numerous and variable, including slowdown in
growth, swing-through gait and progressive tibial bowing, related to skeletal and extraskeletal actions
of FGF23. PHEX gene spans over 220 kb and consists of 22 exons. To date, hereditary and
sporadic mutations are known (missense, nonsense, deletions and splice site mutations).

Case Presentation:
Herein, we describe a male patient carrying a novel de novo mosaic nonsense
mutation c.2176G>T (p.Glu726Ter) located in exon 22 of PHEX gene.

Conclusion:
We highlight this new mutation among possible causative of X-linked hypophosphatemia
and suggest that mosaicism of PHEX mutations is not so uncommon and should be excluded
in diagnostic workflow of heritable rickets both in male and female patients.
Review on the Synthesis of Bio-Active Spiro-Fused Heterocyclic Molecules
Authors: Patel Geetika , Patel Ashok Raj , Kheti Sameera , Sao Parimal Kumar , Rathore Gargee , Banerjee Subhash 
Published: February 2023

Background:
The spiro entity and heterocyclic scaffolds are decorated with a variety of biological and pharmaceutical properties. Therefore, the fusion of spiro compounds with individual moieties. Thus, the designing and expansion of the methods for the synthesis of various spiro-fused heterocyclic scaffolds are significantly important for synthetic organic chemistry.

Methods:
A variety of spiro-fused heterocyclic scaffolds are synthesized through different strategies and methods, such as one-pot multi-components synthesis, and multi-step methods via different organic reactions.

Results:
The wide range of the applications and their interesting biological and medicinal properties encouraged the interest of the researchers to design and construct advanced strategies and methodologies for synthesizing novel spiro-fused heterocyclic molecules which resulted in the publication of numerous research papers and review articles in the literature. In this review article, we have access to the various schemes for the synthesis of different spiro-fused heterocyclic molecules and their biological importance.
Determination of Olmesartan in Bulk and Pharmaceutical Dosage Forms
through the Development and Validation of Stability-indicating RP-HPLC
Method
Authors: Sahu Jagdish K. , Agrawal Akshita A. , Dawre Shilpa , Kanugo Abhishek 
Published: February 2023

Background:
Angiotensin II type 1 (AT 1) receptor antagonist (angiotensin receptor
blocker (ARB) called Olmesartan medoxomil (OLM) prevents angiotensin II from acting on the
renin-angiotensin-aldosterone pathway, which is a crucial factor in the development of hypertension.
OLM is reported to rapidly hydrolyze into its active metabolite, Olmesartan, in plasma after
oral treatment.

Objective:
The objective of the ongoing study was to develop an easy-to-use, precise, and reliable
RP-HPLC method for the determination of Olmesartan in bulk as well as pharmaceutical dosage
forms.

Methods:
The stability indicating HPLC method for assay includes the use of Kromasil 100-5-C8
(100 mm × 4.6 mm) column, UV detector 265 nm, and mobile phase composition was a mixture of
Acetonitrile: water (70:30) and flow rate of 1.0 mL/min. ICH guidelines were followed in the
method's validation. To assess the method's specificity and stability in showing characteristics, stress
degradation studies were carried out. The working standard solution of Olmesartan was exposed to
0.1 N HCl at room temperature, 0.1 N NaOH at room temperature, 30 percent hydrogen peroxide
by volume, and UV radiation in order to conduct a degradation study.

Results:
The retention periods of the drug were found to be 1.36 and 1.47 min for standard and
sample solutions, respectively. The degradation behaviour of drug under different conditions was
studied. The drug was found susceptible to acidic, alkaline and oxidative conditions while it was
found stable in photolytic condition. The developed stability-indicating RP-HPLC method for
assay was validated as per ICH Q2 guidelines and the validation parameters such as accuracy,
precision and specificity were obtained within the accepted criteria.

Conclusion:
It may be concluded that this method is stability-indicating and specific and can successfully
be applied to analyze tablet dosage form containing Olmesartan.
PENGEMBANGAN APLIKASI WEB RILEKS DAN SARUNG TANGAN KOGNITIF SEBAGAI TERAPI PENYEMBUHAN SISWA SMK TEKNIK SIPIL PASCA OPERASI STROKE DI PT XYZ
Authors: Pratama Aldi Adi , Yulianto Kiki 
Published: February 2023

Pendidikan terapan pasca kelulusan dari jenjang SMK, harus memiliki perpaduan antara struktur konsep teori yang diterima dengan keahlian maupun keterampilan. Siswa memiliki peluang besar dalam mendongkrak perekonomian ketika negara berusaha bangkit dari keterpurukan ekonomi pandemi, melalui inovasi dan karya cipta. Namun amanat tersebut terganjal dengan faktor risiko kesehatan, akibat dari bawaan budaya tetap berada di rumah di kala pandemi, sehingga aktivitas olahrga dikatakan kurang. Permasalahn ini diperparah dengan meningkatnya penderita stroke akibat siswa lebih memilih junk food saat pandemi. Stroke trombotik merupakan kondisi penyumbatan lumen pembuluh darah pada bagian otak, karena trombus yang semakin lama kian menebal, sehingga aliran darah menjadi tidak lancar Aplikasi Web Rileks dan Sarung Tangan Kognitif sebagai Rehabilitasi Pasca Operasi Stroke berfokus pada pergerakan jari tangan secara lambat sebagai bentuk terapi kepada siswa stroke pasca operasi. Penciptaan Aplikasi menggunakan perkembangan prototype sederhana. Penciptaan karya memiliki dua metode terapi rehabilitasi fungsional, yakni terapi tangan pada pergerakan jari-jari siswa dan komunikasi AIUEO dengan penderita stroke jenis trombotik. Pengukuran data terapi gerak tangan Range Of Motion (ROM), menggunakan skala 0 (zero) hingga 5 (Normal). ROM adalah latihan yang diberikan untuk mempertahankan atau memperbaiki kembali fungsinya secara normal dan untuk meningkatkan massa otot dan tonus otot pada anggota gerak tubuh. Pengembangan aplikasi mengedepankan aspek psikologis, penyembuhan bertahap serta komunikasi. Perakitan robotik sarung tangan menggunakan rangkaian umum hand exoskeleton, flex sensor, fuzzy logic, dan amplitude stimulus. Hasil Observasi data yang dilakukan selama 6 hari terhadap dua siswa, menunjukan peningkatan ROM dari angka 4 (Good) menuju 5 (Normal) di hari ketiga dan kelima.
Virtual Reality Intervention for Patients With Neck Pain: Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Guo Qifan , Zhang LIMing , Gui Chenfan , Chen Guanghui , Chen Yi , Tan Huixin , Su Wei , Zhang Ruishi , Gao Qiang 
Published: February 2023

Background
Neck pain is a prevalent condition that causes an enormous health care burden due to the lack of efficient therapies. As a promising technology, virtual reality (VR) has shown advantages in orthopedic rehabilitation. However, there is no meta-analysis evaluating the effectiveness of VR in neck pain management.

Objective
This study aims to review original randomized controlled trials (RCTs) evaluating the effectiveness of VR for neck pain and to provide evidence for the clinical application of a new alternative approach for pain management.

Methods
A total of 9 electronic databases were systematically searched for relevant articles published from inception to October 2022. RCTs in English or Chinese that investigated VR therapy for participants with neck pain were included. The methodological quality and the evidence level were assessed using the Cochrane Back and Neck Risk of Bias tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guideline, respectively.

Results
A total of 8 studies with 382 participants were included for the final analysis. For the pain intensity, the overall pooled effect size was 0.51, with a standardized mean difference (SMD) of −0.51 (95% CI −0.91 to −0.11; GRADE: moderate), favoring VR therapy compared with controls. Subgroups analyses revealed that significant differences in pain intensity were found in the multimodal intervention (VR in combination with other therapies) than in other interventions (SMD −0.45, 95% CI −0.78 to −0.13; GRADE: moderate), and better analgesic effects were also observed in patients with chronic neck pain receiving VR intervention (SMD −0.70, 95% CI −1.08 to −0.32; GRADE: moderate) and patients treated in the clinic or research unit (SMD −0.52, 95% CI −0.99 to −0.05; GRADE: moderate) than controls. Regarding other health outcomes, the VR experienced less disability, lower kinesiophobia, and greater kinematic function (cervical range of motion, mean and peak velocity). Nevertheless, the follow-up effects of VR therapy on pain intensity and disability were not found.

Conclusions
Existing moderate evidence support VR as a beneficial nonpharmacological approach to improve pain intensity in patients with neck pain, with advantages to multimodal intervention, people with chronic neck pain, and clinic or research unit–based VR therapy. However, the limited quantity and high heterogeneity of the articles limit our findings.

Trial Registration
PROSPERO CRD42020188635; https://tinyurl.com/2839jh8w