bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive Analysis of Conventional and Bioactive Compositions of the Exocarp of Five Mainly‐Planted Ginkgo biloba Varieties
Authors: Zhang Fang , Wang Huimin , Wu Rong , Shi Manman , Dong Qihui , Su Erzheng
Published: January 2025

Ginkgo biloba exocarp, a by‐product of seed production, is produced in an amount of over 75,000 tons annually in China. However, due to the lack of suitable processing methods, it is predominantly discarded as agricultural waste, resulting in a substantial waste of resources. To seek new development directions, this study first comprehensively evaluated the conventional and bioactive compositions of the exocarps of the five mainly planted G. biloba varieties. The results indicated that G. biloba exocarps contained some preponderant bioactive compositions, including ginkgolic acids (54.10–85.42 mg/g), proanthocyanidins (26.62–52.96 mg/g), and polysaccharides (29.72–51.72 mg/g). G. biloba exocarps were also abundant in terpene trilactones (332.63–780.31 µg/g), flavonoids (70.88–109.26 µg/g), and 6‐hydroxykynurenic acid (43.19–302.99 µg/g). The conventional components of G. biloba exocarps were mainly ash, crude fiber, and fat. The contents of starch and protein were lower; thus, G. biloba exocarp exhibits a lower nutritional value. G. biloba exocarps have the potential to be the best resource for the preparation of ginkgolic acids (GAs), proanthocyanidins, and polysaccharides. This study provides a theoretical basis for the development and utilization of G. biloba exocarps.
Essential Oils From Chromolaena odorata (L.) R. M. King and H. Robinson Stem Barks and Leaves: Chemical Analysis, Biological Activity and In Silico Approach
Authors: Trang Vu Minh , Son Ninh The , Luyen Nguyen Dinh , Giang Phan Minh
Published: January 2025

The current study first describes the chemical profiles of essential oils from Vietnamese Chromolaena odorata fresh stem barks and leaves. The gas chromatography‐flame ionization detection/mass spectrometry (GC‐FID/MS) analysis revealed that α‐pinene (6.97%–38.91%), β‐pinene (5.68%–11.64%), geijerene (10.60%–26.68%), germacrene D (9.33%–16.87%), and (E)‐caryophyllene (5.03%–9.12%) were the major compounds. Essential oils showed strong anti‐inflammation against NO (nitric oxidative) production in lipopolysaccharide (LPS)‐stimulated RAW264.7 cells with IC50 values of 42.44–49.01 µg/mL. Two essential oils also exhibited cytotoxicity against four cancer cell lines, K562, HeLa, HepG2, and MCF‐7, antioxidant activity to capture DPPH radicals, and antidiabetics in α‐glucosidase inhibition. Both samples showed varying levels in the antimicrobial experiment, especially the leaf essential oil, which showed strong antibacterial activity against the bacterium Bacillus subtilis with a MIC value of 64 µg/mL. From the molecular docking investigation, geijerene had a higher affinity for cyclooxygenase‐2 (COX‐2) than the other main compounds, whereas germacrene D had the strongest binding affinity for two protein targets, COX‐2, and B. subtilis FtsZ. It was discovered that the main factor stabilizing the bindings of these compounds to the target proteins was hydrophobic interactions.
Self‐Healing Behavior of Metallopolymers in Complex3D‐Structures Obtained by DLP‐Based 3D‐Printing
Authors: Klein Michael , Fesser Patrick , Zechel Stefan , Hager Martin D. , Schubert Ulrich S.
Published: January 2025

This current study focusses on the investigation of the self‐healing abilities of metallopolymers containing different kinds of metal complexes, which were processed by direct digital light processing (DLP) based three‐dimensional (3D) printing. For this purpose, 2‐phenoxyethyl acrylate is mixed with ligand‐containing monomers either based on triphenylmethyl(trt)‐histidine or terpyridine, respectively. Either zinc(II) or nickel(II) salts are successfully applied for a complexation of the ligand monomers in solution and, subsequently, photopolymerization is performed. The thermo‐mechanical properties of the obtained metallopolymers were characterized by differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) as well as dynamic mechanical thermal analysis (DMTA). Multiple damages with defined forces ranging from 20 to 1500 mN were introduced into the 3D‐structures and successfully healed within 24 h at 70 °C or 120 °C, respectively without losing the structural integrity of the overall 3D‐structures. Herein, excellent healing efficiencies up to 97 % were determined. Consequently, these hollow structures not only feature very good self‐healing abilities but also excellent retention of the 3D‐structure at and above the healing temperature.
In Situ Electron Paramagnetic Resonance Investigation of Isotope‐Selective Breathing in MIL‐53 During Dihydrogen Adsorption
Authors: Fernadi Lukman Muhammad , Chetry Sibo , Sarkar Prantik , Bon Volodymyr , Thangavel Kavipriya , Kaskel Stefan , Hirscher Michael , Krautscheid Harald , Pöppl Andreas
Published: January 2025

The development of smart materials capable of separating dihydrogen isotopologues has risen recently. Among potential candidates, the flexible MIL‐53 (Al) has been gaining attention due to its structural flexibility providing the so‐called ‘’breathing mechanism’’ that can be useful to separate hydrogen isotopologues selectively. In the present work, an in situ continuous wave electron paramagnetic resonance investigation has been proven as a sensitive technique to follow the isotopologue‐selective adsorption‐desorption of dihydrogen species on the paramagnetic metal‐doped MIL‐53 (Al0.99Cr0.01) and MIL‐53 (Al0.99V0.01), respectively. The presence of paramagnetic spin probes such as Cr3+ and V4+ inside the MIL‐53 framework allows for monitoring the framework transition including the 2nd transition step that selectively occurs at p>100 mbar when D2 gas is adsorbed on the pores at 23 K. Furthermore, investigation of D2 desorption from MIL‐53 (Al0.99V0.01) by temperature‐dependent hyperfine spectroscopy provides a more detailed analysis of the D2 desorption process on a microscopic scale with respect to the embedded spin probe.
A Multi‐Scale Computational Model of the Hepatic Circulation Applied to Predict the Portal Pressure After Transjugular Intrahepatic Portosystemic Shunt (TIPS)
Authors: Wang Tianqi , Xiang Yi , Wang Jitao , Gu Jiaqi , Yang Ling , Ma Deqiang , Zhu He , Liu Tianyu , Li Chunlong , Zhang Qi , Han Jiahao , Ding Deping , Wang Wei , Li Qianlong , Wan Haoguang , Qi Xiaolong
Published: January 2025

Transjugular intrahepatic portosystemic shunt (TIPS) is a widely used surgery for portal hypertension. In clinical practice, the diameter of the stent forming a shunt is usually selected empirically, which will influence the postoperative portal pressure. Clinical studies found that inappropriate portal pressure after TIPS is responsible for poor prognosis; however, there is no scheme to predict postoperative portal pressure. Therefore, this study aims to develop a computational model applied to predict the portal pressure after TIPS ahead of the surgery. For this purpose, a patient‐specific 0‐3‐D multi‐scale computational model of the hepatic circulation was developed based on preoperative clinical data. The model was validated using the prospectively collected clinical data of 18 patients. Besides, the model of a representative patient was employed in the numerical experiment to further investigate the influences of multiple pathophysiological and surgical factors. Results showed that the difference between the simulated and in vivo measured portal pressures after TIPS was −1.37 ± 3.51 mmHg, and the simulated results were significantly correlated with the in vivo measured results (r = 0.93, p < 0.0001). Numerical experiment revealed that the estimated model parameters and the severity of possible inherent portosystemic collaterals slightly influenced the simulated results, while the shunt diameter considerably influenced the results. In particular, the existence of catheter for pressure measurement would markedly influence postoperative portal pressure. These findings demonstrated that this computational model is a promising tool for predicting postoperative portal pressure, which would guide the selection of stent diameter and promote individualization and precision of TIPS.
Synthesis of Composites of DNA and Boron Cluster‐Metal Complexes and their Assembly into Functional Nanoparticles with Gene Silencing Activity
Authors: Śmiałkowski Krzysztof , Bednarska‐Szczepaniak Katarzyna , Kulik Katarzyna , Suwara Justyna , Grűner Bohumir , Foryś Aleksander , Nawrot Barbara , Leśnikowski Zbigniew J.
Published: January 2025

Herein, we describe a new type of building block for nanoconstruction based on the composite of a boron cluster metal‐complex (metallacarborane) and therapeutic nucleic acid and their assembly into functional nanoparticles with EGFR oncogene silencing activity. In this direction, a method for oligofunctionalization of a metallacarborane, 3,3’‐cobalt‐bis(1,2‐dicarbollide)(−1) ion, and an automated method for synthesis of DNA‐oligonucleotides attached to the metallacarborane core is developed. The obtained building blocks forms nanoparticles with a “chrysanthemum‐like” topology that carry a slowly releasing antisense anti‐EGFR oligonucleotide silencing EGFR gene efficiently in vitro in a pancreatic carcinoma cell line PANC‐1.
Integration of Gastric Cancer RNA‐Seq Datasets Along With PPI Network Suggests That Nonhub Nodes Have the Potential to Become Biomarkers
Authors: Siavoshi Akram , Piran Mehran , Sharifi‐Zarchi Ali , Ataellahi Fatemeh
Published: January 2025

Background

The breakthrough discovery of novel biomarkers with prognostic and diagnostic value enables timely medical intervention for the survival of patients diagnosed with gastric cancer (GC). Typically, in studies focused on biomarker analysis, highly connected nodes (hubs) within the protein–protein interaction network (PPIN) are proposed as potential biomarkers. However, this study revealed an unexpected finding following the clustering of network nodes. Consequently, it is essential not to overlook weakly connected nodes (nonhubs) when determining suitable biomarkers from PPIN.

Methods and Results

In this study, several potential biomarkers for GC were proposed based on the findings from RNA‐sequencing (RNA‐Seq) datasets, along with differential gene expression (DGE) analysis, PPINs, and weighted gene co‐expression network analysis (WGCNA). Considering the overall survival (OS) analysis and the evaluation of expression levels alongside statistical parameters of the PPIN cluster nodes, it is plausible to suggest that THY1, CDH17, TGIF1, and AEBP1, categorized as nonhub nodes, along with ITGA5, COL1A1, FN1, and MMP2, identified as hub nodes, possess characteristics that render them applicable as biomarkers for the GC. Additionally, insulin‐like growth factor (IGF)‐binding protein‐2 (IGFBP2), classified as a nonhub node, demonstrates a significant negative correlation with both groups within the same cluster. This observation underscores the conflicting findings regarding IGFBP2 in various cancer studies and enhances the potential of this gene to serve as a biomarker.

Conclusion

The findings of the current study not only identified the hubs and nonhubs that may serve as potential biomarkers for GC but also revealed a PPIN cluster that includes both hubs and nonhubs in conjunction with IGFBP2, thereby enhancing the understanding of the complex behavior associated with IGFBP2.
Computational Insights into the Mechanism of Lewis Acid‐Catalyzed Alkene‐Aldehyde Coupling
Authors: Meyrelles Ricardo , Brutiu Bogdan R. , Maryasin Boris
Published: January 2025

The Lewis acid‐catalyzed coupling of alkenes and aldehydes presents a modern, versatile synthetic alternative to classical carbonyl addition chemistry, offering exceptional regio‐ and stereoselectivity. In this work, we present a comprehensive computational investigation into the reaction mechanism of this transformation. Our findings confirm the occurrence of an enantioselective transannular [1,5]‐hydride shift step and demonstrate that the enantioselectivity of the reaction arises predominantly from steric clashes between functional groups in the cyclization step. Combining computational and experimental results, we establish that the Lewis acid catalyst facilitates the initial C−O coupling step between the alkene and the activated aldehyde. Investigations into systems with longer alkyl chains reveal that while they follow a similar mechanistic pathway, cyclization becomes kinetically hindered, preventing the reaction from proceeding. These insights illuminate the factors governing reaction outcomes and limitations, paving the way for future developments in this area.
Design of Broadband Doherty Power Amplifier Based on Spoof Surface Plasmon Polaritons
Authors: Zhang Hongbo , Geng Maojia , Crupi Giovanni , Cai Jialin
Published: January 2025

Spoof surface plasmon polariton (SSPP) is a technique for controlling and manipulating electromagnetic waves within the microwave frequency range through ultrathin corrugated metallic strips. According to current research, SSPPs are primarily used for designing passive circuits and single‐ended power amplifiers (PAs). This work employs SSPP theory for the design of a broadband high‐efficiency Doherty power amplifier (DPA). The input and output matching networks of the carrier power amplifier (CPA) and peak power amplifier (PPA) are designed based on SSPP structure in order to improve the back‐off (BO) efficiency of the DPAs. Results of measurements indicate that the proposed height‐variable SSPP‐based DPA achieves a saturated output power of 41.4 dBm and a maximum efficiency of 61.1% within the frequency range of 1.6–2.2 GHz, whereas BO efficiency remains above 51.2%, demonstrating the effectiveness of the proposed techniques.
A Parallel Human and Rat Investigation of the Interaction Between Descending and Spinal Modulatory Mechanisms
Authors: Fieldwalker Anna , Patel Ryan , Zhao Lucy , Kucharczyk Mateusz W. , Mansfield Michael , Bannister Kirsty
Published: January 2025

Background

Healthy individuals demonstrate considerable heterogeneity upon dynamic quantitative sensory testing assessment of endogenous pain modulatory mechanisms. For those who stratify into a ‘pro‐nociceptive profile’ cohort, consisting of inefficient conditioned pain modulation (CPM) and elevated temporal summation of pain (TSP), the optimal approach for balancing the net output of pain modulatory processes towards anti‐nociception remains unresolved. In this translational healthy human and rat study, we examined whether descending modulation countered spinal amplification during concurrent application of a CPM and TSP paradigm alongside pupillometry since pontine activity was previously linked to functionality of endogenous pain modulatory mechanisms and pupil dilation.

Methods

Perceptual (quantitative sensory testing) and spinal neuronal (in vivo electrophysiology) assessment was performed in healthy humans and rats respectively upon application of parallel CPM/diffuse noxious inhibitory controls (cuff algometry) and TSP/wind‐up (pinprick) paradigms alongside pupillometry.

Results

In humans, repetitive pinprick stimulation produced TSP while concurrent application of a noxious conditioning stimulus did not affect pain ratings to a single pinprick stimulus, repetitive stimulation or the wind‐up ratio. In rats, repetitive pinprick produced neuronal wind‐up while concurrent application of a noxious conditioning stimulus inhibited neuronal responses to a single stimulus and repetitive stimulation but not the wind‐up ratio. For pupillometry experiments, dilatory responses did not increase during application of a TSP or CPM paradigm in humans, while reliable rat responses were not obtained.

Conclusions

Under the conditions of our study, spinal amplification mechanisms surpassed descending inhibitory controls while pupillometry did not offer a reliable indicator of endogenous pain modulatory mechanism function.

Significance: In this translational healthy human and rat study, activity in descending inhibitory controls did not counter spinal amplification processes underpinned by wind up. Despite pupil dilation being previously linked to modulatory mechanisms, dilatory responses did not offer a reliable indicator of functionality. For pro‐nociceptive individuals exhibiting inefficient conditioned pain modulation and/or high temporal summation of pain, dampening faciliatory mechanisms rather than augmenting top‐down inhibitory processes may be a more effective pain‐relief strategy.
Sensitive and Fast Simultaneous Voltammetric Determination of Dopamine and Uric Acid Using Simple Screen‐Printed Carbon Electrode Without Pretreatment and Modification
Authors: Niaz Abdul , Arain Muhammad Balal , Soylak Mustafa
Published: January 2025

A simple, commercially available, unmodified screen‐printed carbon electrode (SPCE) was investigated for the simultaneous voltammetric determination of dopamine (D/A) and uric acid (U/A) in a medium of very low concentration of supporting electrolyte for the first time. The ordinary, simple SPCE from DropSens (DS‐SPCE) was found to be able to separate the overlapping peaks of D/A and U/A with a wide peak potential separation of 300 mV in a medium of very low concentration (0.001 M) of NaH2PO4 as supporting electrolyte (buffer of low capacity) at pH 8.0. Medium of low concentration of electrolyte made it possible to expose the bare electrode surface for its high catalytic activity which resulted into a high peak current signals, particularly for D/A. The DS‐SPCE showed excellent electrocatalytic performance than the other SPCE. The effect of electrolyte concentration and pH on the electrocatalytic behavior of electrode were thoroughly discussed. The DS‐SPCE displayed a sensitive results in good linear ranges from 0.1–5 to 6–20 µM for D/A and 0.5–41.5 µM for U/A. The disposable electrode demonstrated better discrimination ability toward the detection of D/A and U/A over ascorbic acid and other potential interfering species. Moreover, the sensor presented sensitive and highly accurate results in human urine samples without preliminary treatment. The DS‐SPCE sensor was found to be simple, efficient, fast, low cost, and greener than the other reported modified sensors, while providing better sensitivities to detect D/A and U/A simultaneously. Thus, the bare, unmodified DS‐SPCE can be a convenient sensing device for the routine analysis of D/A and U/A, without requiring any complex pretreatment and modification steps of the electrode.
On‐Demand Photochemical Modification of Glassy Carbon Surface
Authors: Hesari Mahdi , Workentin Mark S.
Published: January 2025

Chemical modification of carbonaceous materials is a convenient and reliable approach for the permanent fabrication of functional moieties. Among different linkers, diazirines offer a photogenerated reactive carbene that can insert into X–H (X; O, N) and add to π bonds to tether a variety of moieties on the surface of carbonaceous materials. Explicitly, 3‐phenyl‐3‐(trifluoromethyl)‐3H‐diazirine is more thermally and chemically stable within the diazirine family. Here, we synthesized 3‐(ferrocenylalkyloxy)‐3‐(trifluoromethyl)‐diazirine derivatives and utilized them to covalently modify the surface of glassy carbon (GC). The photogenerated carbene enabled the tethering of the ferrocene (Fc) to the surface of a GC electrode (GCE). The modified surface properties were investigated using different electrochemical techniques, ellipsometry spectroscopy, and scanning electron microscopy. Electrochemical surface responses in KCl and Ru(NH3)63+ solutions clearly exhibited ferrocene redox behavior and surface blocking during modification, respectively. Surface analysis results revealed a clear correlation between the thickness and capacitance current of the modified surface. More importantly, the obtained electrochemistry data show substantial chemical stability of the covalently tethered Fc on the GCE surface in both aqueous and nonaqueous media. The presented work offers an approach for the on‐demand photochemical formation of carbene from diazirines to add functionality for applications of modified electrodes in electrocatalysis and sensing.
An Innovative Nanoparticle Modified Carbon Paste Microsensor for Ultrasensitive and Selective Detection of Danofloxacin in Environmental and Urinary Samples
Authors: Amra Siham , Bourouina‐Bacha Saliha , Bourouina Mustapha , Hauchard Didier
Published: January 2025

An ultrasensitive and selective voltammetric microsensor (multiwalled carbon nanotube [MWCNT]/carbon black nanoparticle [nCB])‐modified carbon paste microelectrode (mCPµE) with ultra‐trace level detection limit is designed for the determination of danofloxacin (DAN) in real samples. The (MWCNT/nCB)‐mCPµE consists of a carbon paste cavity microelectrode (MEC) modified with nCBs and MWCNTs. The nanostructure of the different MEC materials are characterized by scanning electron microscopy and electrochemical impedance spectroscopy. Under optimal conditions, a wide linear range (2.5 × 10−9–2.5 × 10−7 mol L−1) is obtained. The detection and quantification limits are estimated at 4.3 × 10−10 and 1.43 × 10−9 mol L−1, respectively. For the measurement of DAN in the presence of many possible interfering chemical molecules, the suggested microsensor demonstrates remarkable selectivity. Analysis of the real samples confirms that the (MWCNT/nCB)‐mCPµE is a suitable electrochemical sensor for the determination of DAN in wastewater and urine samples with satisfactory recoveries of 103.5%–104.6% and relative standard deviations less than 4.93%. Finally, in terms of sustainability (availability of materials used), analytical efficiency (precision and very low limit of quantification), and economic considerations (use of a very small quantity of materials), the proposed method outperforms previously reported methods.
Genesis of the Bailingshan Iron Deposit in Eastern Tianshan, NW China: Constraints From Geology, Geochemistry and Isotopic Compositions
Authors: Zhang Hui , Wang Yin‐Hong , Wang Kang , Zhang Wei , Gu Wen‐Xin , Xia Wen‐Xuan
Published: January 2025

The Bailingshan deposit is located in the Yamansu arc in eastern Tianshan, NW China. As an economically significant iron deposit in the region, Bailingshan is spatially and temporally associated with volcanism and is hosted in the submarine volcanic and volcaniclastic rocks of the Middle Carboniferous Matoutan Formation, suggesting a potential genetic relationship. The trace element compositions of the major ore mineral (magnetite) from iron ores show lower Ga (1.99–10.80 ppm), Zn (10.0–42.8 ppm), V (9.8–17.3 ppm), Ti (21.2–77.8 ppm) and Cr (10.6–31.3 ppm), but higher Ni (21.0–92.8) and Ni/Cr (1.39–5.89). Together with an evaluation of the morphology of orebody, ore fabrics and petrology, we correlate the iron mineralisation at the Bailingshan area with the hydrothermal process. The δ18O values of magnetite span from −1.5‰ to 3.5‰, while the δ34S values of pyrite sulphides range from 1.7‰ to 7.6‰, demonstrating a wide variation, which suggests that the source components of the ore‐forming materials originated from a mixture of magma and seawater. In addition, the Pb isotopic compositions of pyrite are similar to those of igneous rocks (e.g., dacitic tuff and granodiorite) at Bailingshan, suggesting a common Pb isotope origin. Based on the results of this study, it is proposed that primary magmatic‐hydrothermal fluids, which interacted with infiltrating seawater, played a crucial role in the significant iron mineralisation observed at Balingshan.
Exploratory Research: Patient‐Reported Factors Contributing to Decreased Oral Intake During Radiotherapy in Head and Neck Cancer
Authors: Vergauwen Alice , Baudelet Margot , Van den Steen Leen , Goeleven Ann , Nuyts Sandra , Nevens Daan , Massonet Hanne , Duprez Fréderic , Van Nuffelen Gwen
Published: January 2025

Background

Radiotherapy (RT) in head and neck cancer (HNC) can cause multiple side effects such as nausea, pain, taste loss, fatigue, oral mucositis, xerostomia, and acute radiation‐associated dysphagia (RAD). These factors threaten patients' oral intake (OI) during this RT. Reduced OI can cause weight loss, dehydration, malnutrition, and various comorbidities. On top, reduced OI significantly affects quality of life and may contribute to RAD through the disuse of swallowing muscles. With the aim of maximizing the retention of a patient's OI, it is important to gain an insight into the factors that have the greatest impact. Therefore, this study aims to identify the impact of contributing factors on decreased OI during RT.

Methods

During their treatment, 55 HNC patients completed an OI questionnaire at 5 different time points: during weeks 1, 2, 3, and 4 and at the end of RT (week 7). First, patients rated the OI compared to pre‐RT on a 100 mm visual analogue scale (VAS). Subsequently, patients reported on separate VAS the degree to which pain, fatigue, loss of taste, loss of smell, loss of interest in food, nausea, and loss of hunger contributed to the decrease in OI (0: no contribution; 100: complete contribution). SPSS version 27 was used to analyze the results.

Results

OI decreased over time during RT, with the lowest OI at the end of RT. During the first 4 weeks of RT, the impact of all factors with pain, loss of taste, loss of interest in food, and loss of hunger pointed out as strongest contributing factors to a decreased OI. The most important patient‐reported impacting factor on OI was loss of taste. At the end of RT, the importance of pain and nausea still increases, while the contribution of the other factors drops slightly.

Conclusion

This cohort study shows that several factors contribute to a decreased OI in HNC patients during RT. This study is the first prospective analysis to identify self‐reported factors contributing to reduced OI. Results demonstrate that taste has the greatest impact on OI followed by loss of interest in food, loss of hunger, and pain.
A Case Report of a Mixed‐Methods Assessment of Patient Experiences to Inform Quality Improvement in an Emergency Department in Argentina
Authors: Grande Ratti María Florencia , De Masi Noelia , Garfi Leonardo , Hornstein Lucila , Rochina Esteban , Rodriguez Maria De La Paz , Pedretti Ana Soledad , Martinez Bernardo Julio
Published: January 2025

The objective of this paper is to explore how an emergency department in Argentina collected patient experience perspectives using varied tools to inform improvement activities. A case report of a mixed‐methods assessment of patient experiences to inform quality improvement in an Emergency Department in Argentina. This study was conducted from July 2022 to December 2023 at Hospital Italiano de Buenos Aires, Argentina. Data collection was based on different resources: (a) Net Promoter Score Survey; (b) Buyer Persona, defined as a semi‐fictional representation of your ideal customer based on market research and real data about your existing customers; (c) Empathy Maps, a tool which aids in understanding another person's perspective and empathises with the thoughts, feelings, needs, and behaviours; (d) Customer Journey Map, a visual representation that outlines the various stages and touchpoints a customer goes through when interacting with service. Data was analysed following an iterative process (plan→act→observe→reflect). Its analysis served to understand and improve the design, development, and implementation plans. The results helped to model the patient's journey pattern and understand users' profiles. Therefore, we used the information to support the organisation's improvement process. For example, although wait time is a major driver in this setting, provider and staff communication is critically important. Excellent communication and perceived empathy mitigate long waits, overcrowded environments, and other challenges (such as infrastructure and comfort). This case example can guide the future efforts of healthcare managers and key stakeholders in making decisions about how a service can use empathy‐based tools to improve the patient experience.
An Open‐Label Phase II Trial of Pembrolizumab, an Immune Checkpoint Inhibitor Alone or in Combination With Oral Azacitidine as Second‐Line Therapy for Advanced Head and Neck Squamous Cell Cancers
Authors: Ramani Vinod K. , Gayen Srimonta , Naik Radheshyam
Published: January 2025

Background and Aims

Sensitivity to immune checkpoint inhibitor (ICI) therapy depends in part on the genetic and epigenetic makeup of cancer cells, and CD8 T‐lymphocytes that mediate immune responses. Epigenetics are heritable reversible changes in gene expression that occur without any changes in the nuclear DNA sequence or DNA copy number.

Primary Objective

i. To determine if non‐cytotoxic oral azacytidine when combined with pembrolizumab can improve ORRs of ICI treatment in patients with recurrent/metastatic tumors of head and neck region.

Secondary Objectives

i. To evaluate the clinical effectiveness endpoints and toxicity of oral azacytidine when combined with pembrolizumab. ii. To assess the induction of a T‐cell response among the study subjects. iii. To examine the hypotheses on the predictive biomarkers of response to pembrolizumab, and the mechanisms of resistance.

Methods

Our trial is a Phase 2 randomized study of immunotherapy drug pembrolizumab given in combination with azacitidine (HMA). The intervention model includes “Parallel assignment,” with the primary purpose of the trial being treatment. The primary effectiveness endpoint is overall RECIST‐defined response. To accomplish this goal, 232 patients will be randomized 1:1 (116 in each arm), respectively, to azacitidine plus pembrolizumab or pembrolizumab only groups.

Results

In this trial, molecular profiling of tumor and peripheral blood samples will be conducted which will enable in gaining biological insights for survival benefit. The expected primary outcome assessed at a time frame of 2 years includes the objective response rate of patients measured as per RECIST 1.1 criteria. The secondary outcomes assessed at 2 years include progression‐free survival, time to progression, overall survival, and incidence of treatment‐emergent adverse events.

Conclusion

The findings of this trial will have translational implications, in terms of immune reprogramming induced by epigenetic therapy among a subset of advanced H & N cancer patients in a clinical setting.
The Impact of Audience Response System in Changing Students' Attitudes Towards Lectures During Training Courses; A Before‐After Study
Authors: Zareie Farzad , Baghaei Rahim , Sheykhi Naser , Rasouli Davood
Published: January 2025

Background and Aims

The primary teaching approach known as “traditional lecture” has drawbacks, including being dull and reducing student participation, which has made students feel negatively about it. It seems that by implementing certain changes, active learning techniques like the “Audience Response System” could alter students' perceptions of lectures. The purpose of this study is to find out how employing “ARS” throughout a course has affected nursing students' perceptions of traditional lectures.

Methods

In present research, 44 nursing students participated in quasi‐experimental study (Pretest‐Posttest Design). A 5‐item, 5‐point Likert questionnaire and a pre‐test question regarding the degree of participation during lecture were used to gauge the students' attitudes towards lectures. Following that, a six‐session pharmacology course including “Lectures + ARS” was held. Following the completion of the course, the original questionnaire, a posttest question regarding attitudes, and four 3‐point Likert items regarding students' opinions regarding the use of ARS going forward were used to assess changes in the students' attitudes towards lectures. SPSS Ver. 26 was used for the data analysis. p < 0.05 was taken into consideration as the significance threshold.

Results

In comparison to before the course, the students' attitudes towards lectures had changed in a positive and significant way, specifically in items such as learning quality improvement, decreasing boredom, increasing participation and class activity. However, in the domain of “decreasing the use of lecture,” the ARS had failed to change the students' attitudes. 79.6% of students stated that the ARS had changed their attitudes towards lectures. More than 90% of students agreed with continued use of ARS in the future.

Conclusion

Lecturing could transform from a passive position to an active position by implementing ARS. Lecture + ARS could lead to improvement in students' class participation and activity, both of which are essential factors of an optimal education.
Practical Steps to Design Brucellosis Preventive Interventions: An Intervention Mapping Approach
Authors: Ziapour Arash , Rezaei Farshid , Jafarzadeh Mohammad , Mirzaei Nasim , Moradi‐Asl Eslam , Nejhaddadgar Nazila
Published: January 2025

Background and Aims

Common diseases between humans and animals are one of the health problems of countries, which requires targeted intervention. The intervention mapping model provides guidance for choosing the most appropriate methods and applications. Since one of the most important challenges in the endemic areas of Iran is the control of brucellosis. Therefore, the aim of this research is to examine the intervention mapping model and its steps to design interventions to prevent this disease.

Methods

In this research, the practical steps of the Brucellosis prevention intervention were carried out with the intervention mapping approach in six steps from July 2023 to December 2023. In the first step, needs assessment was done through literature review, semi‐structured in‐depth interview and checklist. In the second step, the matrix of change objectives was designed. After selecting intervention methods based on theory and practical applications, and producing program components and materials, the intervention was implemented and evaluated.

Results

Intervention mapping helped us in designing and implementing the brucellosis control educational program with the participation of participants, specifying the definition of results, performance goals and determinants, theoretical methods, practical applications, intervention design, implementation and step‐by‐step evaluation.

Conclusion

The intervention mapping approach ensures the transparency of all intervention components and it provides a useful approach for developing behavior change interventions.
Retrospective Analysis of Antibiotic Resistance Patterns of Uropathogenic Escherichia coli With Focus on Extended‐Spectrum β‐Lactamase at a Tertiary Central Hospital in Saudi Arabia
Authors: Alameer Khalid M. , Abuageelah Bandar M. , Alharbi Rena H. , Alfaifi Mona H. , Hurissi Eman , Haddad Moayad , Dhayhi Nabil , Jafar Abdulelah S. , Mobarki Mousa , Awashi Hassan , Musawi Shaqraa , Alameer Abdulaziz M. , Kariri Shatha H. , Alhazmi Abdulaziz H.
Published: January 2025

Background and Aims

Urinary tract infections (UTIs) are a prevalent bacterial infection that has substantial implications for healthcare on a global scale. Escherichia coli (E. coli) is a gram‐negative rod responsible for most UTI cases. ESBL‐producing E. coli is widely recognized as a significant contributor to antibiotic resistance. This study aims to evaluate the prevalence and antibiotic resistance trends of ESBL‐producing E. coli in patients with UTIs at a tertiary hospital in Jazan, Saudi Arabia.

Methods

A retrospective cross‐sectional analysis was conducted on 347 urine specimens collected between January 2022 and March 2023.

Results

The study found that 31% of E. coli specimens were positive for ESBL. Among patients with ESBL‐producing E. coli, 78.9% were females, and the majority of ESBL‐producing E. coli cases were observed in the outpatient clinic departments. Among all E. coli isolates, ampicillin exhibited the highest resistance rate at 69.3%, aztreonam at 66.7%, and colistin at the lowest resistance. ESBL‐producing E. coli strains exhibited higher resistance rates than non‐ESBL‐producing E. coli strains.

Conclusion

The study agrees with others in the region and shows a higher prevalence of ESBL‐producing E. coli in the region, emphasizing the importance of antibiotic stewardship programs and infection control measures to mitigate the prevalence and spread of ESBL‐producing E. coli in our region.
Prevalence of Diarrhea Disease and Associated Factors Among Children Under 5 Years in Geshiyaro Project Implementation Sites in Ethiopia: A Cross‐Sectional Study
Authors: Alemu Zinabu Assefa , Girmay Aderajew Mekonnen , Teklu Kirubel Tesfaye , Adugna Ermias Alemayehu , Serte Melaku Gizaw , Alemayehu Tsigereda Assefa , Likasa Badasa Wagari , Collyer Benjamin , Mehari Zelalem , Salasibew Mihretab , Tollera Getachew , Tessema Masresha
Published: January 2025

Background

Globally, infectious diseases such as pneumonia, diarrhea, and malaria are the leading causes of death for children under 5. Diarrheal disease is a significant public health concern and causes the death of approximately 525,000 children under the age of 5 every year. In Ethiopia, studies revealed that the prevalence of diarrhea among children under 5 years is alarming. However, there has been a shortage of studies regarding the predictors of diarrheal disease in Geshiyaro project implementation sites in Ethiopia. Therefore, this study aimed to fill this gap.

Methods

A community‐based cross‐sectional study was conducted from June to July 2023. A total of 2937 participants were enrolled in this investigation. Descriptive and multivariate logistic regression analysis was performed using STATA version 16.

Results

The 2‐week prevalence of diarrhea among children under 5 years was 11.8%. The following factors were significantly associated (p < 0.05) with the occurrence of childhood diarrhea: sex of the child (AOR: 1.6; 95% CI, 1.17–2.19), child age in a month (AOR: 0.5; 95% CI, 0.26–0.94), drinking water service (AOR: 2.6; 95% CI, 1.33–5.25), knowledge on diarrhea prevention (AOR: 1.4; 95% CI, 1.05–1.98), open defecation practice (AOR: 1.9; 95% CI, 1.33–2.74), and rotavirus vaccination (AOR: 1.8; 95% CI, 1.20–2.56).

Conclusions

This study identified several factors contributing to diarrhea. Besides, it also studied and showed a larger number of children who were not receiving basic vaccines. Therefore, the government and partner organizations should implement effective interventions to increase vaccine coverage and reduce diarrhea.
Knowledge, Attitude, and Practice Regarding High Salt Intake and Association With Hypertension Among Rural Women in Chandpur District of Bangladesh
Authors: Chandra Pradip , Islam Aminul , Robertson Shahara , Abu‐Al‐Rafe  , Sayed Md. Abu , Ahona Afra Anjum , Parvin Mst. Nadira , Gupta Pradip Sen
Published: January 2025

Background and Aims

The human body requires a relatively little quantity of sodium to transmit nerve impulses, contract and relax muscles, and maintain appropriate water and mineral balance and which is typically added from diets. The study aimed to assess the level of knowledge, attitude, and practice regarding high salt intake and their association with hypertension among rural women of a selected community in Chandpur.

Methods

A cross‐sectional study was adopted to collect data from 250 households of Chandpur district. The study was conducted during May 2022 to July 2022. The semi‐structured pretested WHO‐modified step‐wise approach to the non‐communicable disease risk factor surveillance (STEPS). Instrument version 3.1 module was used to administer the knowledge, attitude and practice questionnaire to assess the knowledge, attitude and practice of the participants. Binary logistic regression was performed to examine the factor related with knowledge, attitude, and practices.

Results

The result gives evidence that participant who added always salt to their meals were three times more likely to be hypotensive (AOR: 2.99; CI: 1.40, 6.42). Besides, participants who avoid eating outside are significantly less likely (AOR: 0.19; C.I: 0.05 to 0.70) to be hypertensive.

Conclusion

Findings showed that daily salt consumption and “avoid eating out” were significantly associated with hypertension status. These findings imply that further educational intervention is needed to increase understanding of healthy dietary salt intake among rural women.
Perspective on Antibiotic Resistance in Bangladesh: A Critical Yet Overlooked Public Health Crisis
Authors: Hassan Md. Mahadi , Nohor Noushin
Published: January 2025

Background and Aims

This article explores antibiotic resistance as a critical public health issue in Bangladesh, emphasizing its growing threat to the nation's healthcare system. As a developing country, Bangladesh faces unique challenges in managing this crisis, with antibiotic resistance posing significant risks due to its multidimensional problems to both individual health and the broader population.

Methods

We searched for relevant pieces of literature that discuss the antibiotic resistance problem both from a global and national perspective. Based on the importance and our objectives we selected the relevant articles. The perspective was written using the evidence and information available in those articles.

Results

Key factors contributing to the rise of antibiotic resistance include the irrational use and prescription of antibiotics in both healthcare settings and agriculture, incomplete doses of antibiotics, and insufficient public awareness. The article also discusses potential policy recommendations, such as the implementation of stricter antimicrobial stewardship programs, enhanced surveillance systems, and public education campaigns to reduce the misuse of antibiotics.

Conclusion

In conclusion, antibiotic resistance in Bangladesh requires urgent attention and coordinated efforts from all sectors of society to prevent further deterioration of public health and safeguard future generations.
Mechanisms of enhancer‐driven oncogene activation
Authors: Vriend Joyce , Delwel Ruud , Pastoors Dorien
Published: January 2025

An aggressive subtype of acute myeloid leukemia (AML) is caused by enhancer hijacking resulting in MECOM overexpression. Several chromosomal rearrangements can lead to this: the most common (inv(3)/t(3;3)) results in a hijacked GATA2 enhancer, and there are several atypical MECOM rearrangements involving enhancers from other hematopoietic genes. The set of enhancers which can be hijacked by MECOM can also be hijacked by BCL11B. Enhancer deregulation is also a driver of oncogenesis in a range of other malignancies. The mechanisms of enhancer deregulation observed in other cancer types, including TAD boundary disruptions and the creation of de novo (super‐) enhancers, may explain overexpression of MECOM or other oncogenes in AML without enhancer hijacking upon translocation. Gaining mechanistic insight in both enhancer deregulation and super‐enhancer activity is critical to pave the way for new treatments for AML and other cancers that are the result of enhancer deregulation.
An AG‐RetinaNet for Embryonic Blastomeres Detection and Counting
Authors: Zhou Wenju , Talha Ouafa , Han Xiaofei , Liu Qiang , Xu Yuan , Zhang Zhenbo , Yuan Naitong
Published: January 2025

Embryo morphology assessment is crucial for determining embryo viability in assisted reproductive technology. Traditional manual evaluation, while currently the primary method, is time‐consuming, resource‐intensive, and prone to inconsistencies due to the complex analysis of morphological parameters such as cell shape, size, and blastomere count. For rapid and accurate recognition and quantification of blastomeres in embryo images, Attention Gated‐RetinaNet (AG‐RetinaNet) model is proposed in this article. AG‐RetinaNet combines an attention block between the backbone network and the Feature Pyramid Network to overcome the difficulties posed by overlapping blastomeres and morphological changes in embryo shape. The proposed model, trained on a dataset of human embryo images at different cell stages, uses ResNet50 and ResNet101 as backbones for performance comparison. Experimental results demonstrate its competitive performance against state‐of‐the‐art detection models, achieving 95.8% average precision while balancing detection accuracy and computational efficiency. Specifically, the AG‐RetinaNet achieves 83.08% precision, 91.13% sensitivity, 90.91% specificity, and an F1‐score of 86.92% under optimized Intersection Over Union and confidence thresholds, effectively detecting and counting blastomeres across various grades. The comparison between these results and the manual annotations of embryologists confirms that our model has the potential to improve and streamline the workflow of embryologists in clinical practice.
CRYAB is upregulated and predicts clinical prognosis in kidney renal clear cell carcinoma
Authors: Ren Hao , Chen Xinyu , Ji Meiling , Song Wengang , Cao Lili , Guo Xiaohong
Published: January 2025

Clear cell renal cell carcinoma (KIRC) is the most prevalent subtype of renal cell carcinoma (RCC), accounting for 70% to 80% of all RCC cases. The CRYAB (αB‐crystallin) gene is broadly expressed across various human tissues, yet its role in KIRC progression remains unclear. This study aims to elucidate the function of CRYAB in KIRC progression and to assess its potential as a biomarker for early diagnosis, therapeutic targeting, and prognosis. In our report, we found that CRYAB was dramatically upregulated in KIRC, and its expression was associated with TNM stage, pathological stage, and age. Also, patients with higher CRYAB expression exhibited poor survival and prognosis. CRYAB overexpression led to enhanced tumor cell proliferation. Vice versa, CRYAB downregulation resulted in decreased cell proliferation in vitro. Mechanistically, Gene set enrichment analysis plots showed the enrichment of cell survival. Consistently, these effects were associated with increased AKT signaling and BCL‐2 expression. Furthermore, we also observed that CRYAB expression levels were negatively correlated with immunocyte infiltration. In conclusion, these findings suggested that CRYAB could be regarded as a latent biomarker for early diagnosis, therapeutic targeting, and prognosis.
Exchange Rates, Uncovered Interest Parity, and Time‐Varying Fama Regressions
Authors: Fu Bowen , Li Mengheng , Haque Qazi
Published: January 2025

This paper studies the forward premium puzzle, which signals a violation of the uncovered interest parity (UIP) hypothesis. We test this hypothesis with Fama‐style regressions with time‐varying parameters (TVPs) and stochastic volatility (SV) on six major currencies relative to the US dollar on monthly samples from 1993 to 2018. TVP‐SV regressions are also employed to examine the opposing predictions of the forward premium and excess volatility puzzles often found in exchange rate risk premiums and interest rate differentials. Using Bayesian methods, we document that the riskiness of exchange rates explains the forward premium puzzle, while a liquidity premium reconciles the contrasting predictions of the forward premium and excess volatility puzzles.