bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advances in computational and experimental approaches for deciphering transcriptional regulatory networks
Authors: Moeckel Camille , Mouratidis Ioannis , Chantzi Nikol , Uzun Yasin , Georgakopoulos‐Soares Ilias 
Published: May 2024

AbstractUnderstanding the influence of cis‐regulatory elements on gene regulation poses numerous challenges given complexities stemming from variations in transcription factor (TF) binding, chromatin accessibility, structural constraints, and cell‐type differences. This review discusses the role of gene regulatory networks in enhancing understanding of transcriptional regulation and covers construction methods ranging from expression‐based approaches to supervised machine learning. Additionally, key experimental methods, including MPRAs and CRISPR‐Cas9‐based screening, which have significantly contributed to understanding TF binding preferences and cis‐regulatory element functions, are explored. Lastly, the potential of machine learning and artificial intelligence to unravel cis‐regulatory logic is analyzed. These computational advances have far‐reaching implications for precision medicine, therapeutic target discovery, and the study of genetic variations in health and disease.
Development of time‐resolved fluoroimmunoassay with enhanced fluorescence reaction for the quantitation of atezolizumab in plasma
Authors: Darwish Ibrahim A. , Alzoman Nourah Z. , Khalil Nehal N. , Alsalhi Mohammed S. 
Published: May 2024

AbstractAtezolizumab (ATZ) is a human monoclonal antibody, which has been granted multiple approvals from the US Food and Drug Administration (FDA) for the immunotherapy of different types of cancer. This study describes the prototype of a time‐resolved fluoroimmunoassay (TRFIA) for the quantitation of ATZ in plasma. The assay involved the non‐competitive binding of ATZ to its specific antigen [programmed death‐ligand 1 (PD‐L1) protein]. The immune complex formed on the inner surface of the assay plate wells was quantified by anti‐human secondary antibody labeled with a chelate of europium‐ethylenediaminetetraacetic acid. The enhanced fluorescence signal was generated by an enhanced fluorescence solution composed of thenoyltrifluoroacetone, trioctylphosphine oxide, and Triton X‐100. The conditions of the TRFIA were refined, and its optimum procedures were established. The assay was validated in accordance with the immunoassay validation guidelines, and all the validation parameters were acceptable. The working range of the assay was 20–1000 pg mL−1, and its limit of quantitation was 20 pg mL−1. The assay was applied to the quantitation of ATZ in plasma samples with satisfactory accuracy and precision. The proposed TRFIA has significant benefits over the existing methodologies for the quantitation of ATZ in clinical settings.
Role of the prefrontal cortical protease TACE/ADAM17 in neurobehavioral responses to chronic stress during adolescence
Authors: Sharafeddin Fransua , Sierra Julio , Ghaly Mina , Simon Timothy B. , Ontiveros‐Ángel Perla , Edelbach Brandon , Febo Marcelo , Labus Jennifer , Figueroa Johnny D. 
Published: May 2024

AbstractIntroductionChronic adolescent stress profoundly affects prefrontal cortical networks regulating top‐down behavior control. However, the neurobiological pathways contributing to stress‐induced alterations in the brain and behavior remain largely unknown. Chronic stress influences brain growth factors and immune responses, which may, in turn, disrupt the maturation and function of prefrontal cortical networks. The tumor necrosis factor alpha‐converting enzyme/a disintegrin and metalloproteinase 17 (TACE/ADAM17) is a sheddase with essential functions in brain maturation, behavior, and inflammatory responses. This study aimed to determine the impact of stress on the prefrontal cortex and whether TACE/ADAM17 plays a role in these responses.MethodsWe used a Lewis rat model that incorporates critical elements of chronic psychosocial stress, such as uncontrollability, unpredictability, lack of social support, and re‐experiencing of trauma.ResultsChronic stress during adolescence reduced the acoustic startle reflex and social interactions while increasing extracellular free water content and TACE/ADAM17 mRNA levels in the medial prefrontal cortex. Chronic stress altered various ethological behavioral domains in the observation home cages (decreased ingestive behaviors and increased walking, grooming, and rearing behaviors). A group of rats was injected intracerebrally either with a novel Accell™ SMARTpool TACE/ADAM17 siRNA or a corresponding siRNA vehicle (control). The RNAscope Multiplex Fluorescent v2 Assay was used to visualize mRNA expression. Automated puncta quantification and analyses demonstrated that TACE/ADAM17 siRNA administration reduced TACE/ADAM17 mRNA levels in the medial prefrontal cortex (59% reduction relative to control). We found that the rats that received prefrontal cortical TACE/ADAM17 siRNA administration exhibited altered eating patterns (e.g., increased food intake and time in the feeding zone during the light cycle).ConclusionThis study supports that the prefrontal cortex is sensitive to adolescent chronic stress and suggests that TACE/ADAM17 may be involved in the brain responses to stress.
From crisis to prosperity: Leveraging robots, artificial intelligence, and service automation for sustainable tourism in Zimbabwe
Authors: Chiwaridzo Option Takunda , Chiwaridzo Shingirirai 
Published: May 2024

AbstractIn an increasingly digital and interconnected world, the integration of advanced technologies such as robotics, artificial intelligence (AI), and service automation has become pivotal for shaping the future of various industries, including tourism. The paper investigates complex relationship between three independent variables: (robotic adoption, AI adoption, and service automation adoption) and three dependent variables: (social sustainability, economic sustainability, and environmental sustainability). Employing a quantitative research approach, the study gathered data from 608 randomly selected tourism supply chain stakeholders using the Krejcie and Morgan table to determine the sample size. Data collection was facilitated through Google Forms questionnaires, and the analysis relied on structural equation modeling. The statistical findings highlight positive direct significant relationships among these variables, as evidenced byt‐statistic values surpassing the threshold of 1.96. These values ranged from a minimum of 2.156 to a maximum of 10.083. These results suggest that by strategically integrating these technologies, tourism businesses and policymakers in Zimbabwe can enhance tourist experience, the industry's long‐term viability and its positive impact on society, the economy, and the environment. This study's outcomes provide a compelling foundation for informed decision‐making and the development of targeted strategies aimed at advancing sustainability objectives within the Zimbabwean tourism landscape.
Regulation of Oxidative Stress and Apoptosis in Streptozotocin‐Induced Diabetic Rats by Egyptian Sidr Honey
Authors: El‐Aarag Bishoy , Shehata Sahar Bahgat , El‐Garawani Islam M. , El‐Seedi Hesham R. , Nofal Amany Ebrahim 
Published: May 2024

AbstractDiabetes mellitus is a global health issue characterized by hyperglycemia which leads over time to severe damage to numerous tissues. The present study aimed to estimate the effect of Egyptian Sidr honey against streptozotocin (STZ)‐induced diabetes in rats. Diabetic rats were treated with Sidr honey daily for 4 consecutive weeks. The biochemical profile of blood samples was measured. Furthermore, the activity of antioxidant enzymes, nitric oxide (NO), and malonaldehyde (MDA) were examined in hepatic and pancreatic tissues. Moreover, the expression of Bax, Caspase‐3, and Bcl2 proteins were measured. Results revealed that the capability of Sidr honey to decline the elevated blood glucose and fructosamine levels. Also, the honey decreased the levels of NO and MDA. Furthermore, it regulated the antioxidant enzymes activity. Moreover, it reduced the expression levels of Caspase‐3 and Bax while increased the Bcl2 level. In conclusion, Sidr honey can regulate hyperglycemia, oxidative stress, apoptosis, and antioxidant enzymes in STZ‐induced diabetic rats.
Rationally Designed Peptoid Inhibitors of Amyloid‐β Oligomerization
Authors: Waugh Mihyun Lim , Wolf Lauren M. , Moore Kelly A. , Servoss Shannon L. , Moss Melissa A. 
Published: May 2024

AbstractWhile plaques comprised of fibrillar Aβ aggregates are hallmarks of Alzheimer's disease, soluble Aβ oligomers present higher neurotoxicity. Thus, one therapeutic approach is to prevent the formation of Aβ oligomers and reduce their associated harmful effects. We have proposed a peptoid mimic of the Aβ hydrophobic KLVFF core as an ideal candidate aggregation inhibitor due to its ability to evade proteolytic degradation via repositioning of the side chain from the α‐carbon to the amide nitrogen. This peptoid, JPT1, utilizes chiral sidechains to achieve a helical structure, while C‐terminal addition of two phenylalanine residues places aromatic groups on two sides of the helix with spacing designed to facilitate interaction with amyloid β‐sheet structure. We have previously shown that JPT1 modulates Aβ fibril formation. Here, we demonstrate that JPT1 also modulates Aβ oligomerization, and we explore the role of the charge on the linker between the KLVFF mimic and the extended aromatic residues. Additionally, we demonstrate that peptoid‐induced changes in Aβ oligomerization correlate with attenuation of oligomer‐induced nuclear factor‐κB activation in SH‐SY5Y human neuroblastoma cells. These findings support the therapeutic potential of peptoids to target early stages of Aβ aggregation and impact the associated Aβ‐induced cellular response.
A case of cytomegalovirus colitis initially misdiagnosed as colonic ischemia in an immunocompetent Japanese woman
Authors: Hamano Atsuro , Harada Shunsuke , Kobayashi Takaaki , Moody Sandra , Yoshida Akihito 
Published: May 2024

Key Clinical MessageCytomegalovirus colitis should be considered in a patient presenting with bloody stool even among immunocompetent patients.
Neuromyelitis optica spectrum disorder co‐existing with antiphospholipid syndrome: A case report
Authors: Edwin Gidion , Msagati Francis , Komanya Francisca , Alphonce Baraka , Meda John , Nyundo Azan 
Published: May 2024

Key clinical messageNeuromyelitis optica spectrum disorder is an autoimmune disease, rarely presents with antiphospholipid syndrome. Diagnosis and management of NMOSD are challenging in the background of diverse presentations, especially in resource‐limited settings.AbstractNeuromyelitis optica spectrum disorder (NMOSD) is a progressive demyelinating autoimmune condition resulting from the autoantibodies produced against aquaporin‐4 (AQP‐4) proteins which are widely distributed in astrocytes in the nervous system. In the setting of NMOSD, it is very crucial to consider other autoimmune diseases as differential diagnoses or co‐occurrences due to the diversity of symptoms. NMOSD co‐exists with other autoimmune diseases such as myasthenia gravis, thyroid disease, ankylosing spondylitis, pernicious anemia, thrombotic thrombocytopenic purpura, ulcerative colitis, and systemic lupus erythematosus. Few cases of antiphospholipid syndrome co‐existing with NMOSD have been reported. In resource‐limited settings, the published data are scarce, and therefore, autoimmune diseases are poorly studied. Therefore, late diagnosis and delayed treatment initiation pose long‐term sequelae and hence poor prognosis. Here, we present a case of an African woman in her early 40s presenting with bilateral progressive loss of vision, transverse myelitis, extensive longitudinal hyperintense T2 cervical lesion, and AQP‐4 autoantibody keeping with NMOSD. The co‐existence of antiphospholipid syndrome, in this case, was supported by a history of recurrent pregnancy loss and positive antiphospholipid antibodies. This case underscores the importance of individualized‐based medicine, especially in resource‐limited settings.
Bilateral breast tuberculosis: A case report
Authors: Molla Yohannis Derbew , Iberahim Mohammed Alemu , Alemu Hirut Tesfahun , Abera Samuel Addisu 
Published: May 2024

Key Clinical MessageBreast tuberculosis is a rare clinical condition that has the potential to imitate breast cancer or pyogenic abscess. It is crucial to consider this in patients who have resistant breast abscesses or persistent sinuses, particularly in high‐risk groups or locations. The main treatment for breast tuberculosis is antitubercular treatment.AbstractBilateral breast tuberculosis is a rare form of the disease that affects breasts. It is most commonly seen in young females, including nulliparous and lactating women. Diagnosis of bilateral breast tuberculosis can be challenging due to its similarity to other breast diseases, such as granulomatous mastitis and breast carcinoma. Patients from high‐risk groups and/or endemic locations who present with clinically suspicious breast lumps or refractory breast abscesses should have breast TB taken into consideration in their differential diagnosis. A 24‐year‐old Ethiopian female presented to the surgical outpatient department with a complaint of bilateral breast pain of 1‐year duration associated with a low‐grade fever, not associated with chills or rigor. She also has ulceration on the lower part of both breasts. It was followed by pus discharge from the right breast 6 months later. Investigations, including fine needle aspiration cytology, were suggestive of tuberculous mastitis. Later, the patient was treated with antituberculous drugs for 6 months, and the above symptoms subsided. Individuals with breast lesions who do not respond well to antibiotics should be suspected of having breast tuberculosis, especially if they are young and reside in or were born in a nation where the disease is prevalent.
Diffuse type gastric adenocarcinoma with atypical presentation: A case report
Authors: Edwin Gidion , Mbishi Yohana , Zerd Francis , Komanya Francisca , Alphonce Baraka , Sindato Emmanuel 
Published: May 2024

Key Clinical MessageGastric adenocarcinoma can present uncommonly. This emphasizes the need for intensified vigilance in the absence of typical gastrointestinal symptoms, particularly in areas where infectious diseases are common.AbstractGastric adenocarcinoma, a common advanced‐age global malignancy is typically associated with abdominal symptoms. However, atypical presentations such as back pain and respiratory distress particularly in younger patients represent diagnostic challenges. We present a case of a late‐30s male who presented initially with back pain, shortness of breath, and constitutional symptoms. A diagnosis of tuberculosis was established presumptively with immediate initiation of treatment. Later on, he presented with abdominal pain and intractable vomiting. Oesophagoduodenoscopy (OGD), tissue histology, and immunohistochemistry confirmed a diffuse type gastric adenocarcinoma. He died as a result of complications from an advanced disease. This particular instance emphasizes the importance of maintaining a high index of skepticism even in atypical presentations, as well as the significance of prompt OGD alongside potential genetic testing if any. Gastric adenocarcinoma should be contemplated by clinicians in a variety of clinical scenarios, especially when handling younger patients from settings with limited resources to facilitate timely diagnosis and effective treatment.
Hereditary epidermolytic palmoplantar keratosis due to a novel desmoglein‐1 mutation: A case report
Authors: Koschitzki Kevin , Kurz Bernadett , Schreml Julia , Fischer Judith , Hotz Alrun , Hammers Christoph M. , Berneburg Mark , Niebel Dennis , Schreml Stephan 
Published: May 2024

Key Clinical MessageKeratosis palmoplantaris striata type I (SPPK‐I) is a rare autosomal‐dominant type of hereditary epidermolytic palmoplantar keratoderma, which can be caused by mutations in desmoglein‐1 (DSG‐1). Patients suffer from hyperkeratotic plaques and painful palmoplantar fissures. Unfortunately, treatment options including salicylic vaseline, topical corticosteroids, phototherapy, and retinoids are inefficient.AbstractHereditary palmoplantar keratodermas (PPKs) represent a heterogeneous group of rare skin disorders with epidermal palmoplantar hyperkeratosis. Mutations in the desmoglein 1 gene (DSG1), a transmembrane glycoprotein, have been reported primarily in striate PPKs. We report a patient with keratosis palmoplantaris striata type I (SPPK‐I) with a specific pathogenic variant [c.349C>T, p.(Arg117*)] in DSG1. Despite increased understanding, effective treatment options for PPK, including SPPK‐I, remain limited.
Direct and TEMPO‐Mediated Electro‐Oxidation of 5‐(Hydroxymethyl)furfural in Organic and Hydro‐Organic Media
Authors: Vo Nhat Tam , Cacciuttolo Quentin , Pasquier David , Larmier Kim 
Published: May 2024

AbstractBiomass‐derived 5‐hydroxymethyl furfural (5‐HMF) is a promising starting substrate for producing two high value‐added products 2,5‐diformylfuran (DFF) and 2,5‐furandicarboxylic acid (FDCA). DFF, which is produced by selectively oxidizing the hydroxymethyl group of 5‐HMF to an aldehyde group, has many applications in pharmaceuticals, macrocyclic ligands and fluorescent materials. Oxidizing both aldehyde and hydroxymethyl groups of 5‐HMF leads to FDCA, which is an important monomer in the production of a bioplastic polyethylene furanoate polymer. Electrochemical conversion of 5‐HMF is a potential route for sustainable chemical production of DFF and FDCA. In fact, using 2,2,6,6‐tetramethyl‐ piperidine‐1‐oxyl (TEMPO) as a redox mediator leads to a highly efficient and selective electro‐oxidation of 5‐HMF into FDCA in a basic buffer solution. In this report, the direct and TEMPO‐mediated electro‐oxidation of 5‐HMF was investigated in various organic and hydro‐organic media at room temperature. Direct electro‐oxidation leads to a low selective conversion of 5‐HMF to DFF (10 % of yield) and the formation of unwanted products such as formic acid and protoanemonin (90 % and 37 % of yield respectively) in acetonitrile. Electrocatalytic 5‐HMF conversion in the presence of TEMPO as a redox mediator achieved a near‐quantitative yield of DFF in acetonitrile and γ‐valerolactone. Importantly, we demonstrate the role of water in the conversion of aldehydes to carboxylic acids.
Chiroptically active copper clusters as platform for enantioselective detection of lysine
Authors: Dutta Camelia , Nataraajan Ragul Vivaz , Kumar Jatish 
Published: May 2024

AbstractMetal clusters have drawn considerable research attention over the years due to their fascinating optical properties. Owing to their appealing photophysical characteristics, these materials have drawn attention as potential candidates for various application in diverse fields, including disease detection, biosensing, chemical sensing, and the fabrication of light‐harvesting materials. Presently, there is an increasing research focus on the use of clusters in biomedical research, both as biodetection platform and as bioimaging agents. Of special interest are chiral clusters, which can selectively interact with chiral biomolecules owing to their optical activity. Herein, we showcase the use of a pair of chiroptically active copper clusters for the enantioselective detection of lysine, an amino acid of vast biological relevance. Two techniques are concurrently employed for the detection of lysine at varying concentrations. Circular dichroism serves as a potent tool for detecting lysine at low concentrations, whereas luminescence is effectively employed as a detection method for high analyte concentrations. The combined electronic impact of clusters and lysine resulted in the emergence of an enhanced enantioselective Cotton effect at specific wavelength.
Numerical simulation of natural convection in a rectangular enclosure filled with porous medium saturated with magnetic nanofluid using Buongiorno's two‐component model
Authors: Venkatadri K. , Murthy K. V. Narasimha , Bég Tasveer A. , Bég O. Anwar , Kuharat Sireetorn 
Published: May 2024

AbstractMotivated by studying emerging nanofluid‐based magnetic fuel cells and hybrid direct absorber solar collectors, a numerical study is presented for buoyancy‐driven flow in a vertical enclosure containing a porous medium saturated with magnetized nanofluid flow under a transverse static magnetic field. The enclosure features adiabatic side walls and vertical heat slits, ensuring consistent cold temperatures on the lower and upper bounded walls. The side walls of the regime are insulated, and the hot slits are centrally located on these walls. The finite difference method (FDM) is applied to employ the transformed dimensionless vorticity–stream function (VSF) formulation of the transport equations. The impact of pertinent parameters on isotherm, streamline, iso‐concentration, and average Nusselt and Sherwood numbers are visualized with contour plots and graphs. Increasing Darcy number values tend to amplify the isotherm magnitudes. Higher Hartmann (magnetic) number values, on the other hand, lead to a reduction in local Nusselt number profiles but do not significantly modify the local Sherwood number. The porous medium permeability, as simulated via the Darcy number, has a strong impact on streamlines, thermal contours, and iso‐concentrations. A reduction in Darcy's number suppresses local Nusselt and Sherwood numbers, whereas an elevation in Rayleigh's number enhances them. Increasing the Buongiorno nanoscale Brownian motion parameter enhances local Nusselt and Sherwood numbers at both cold walls of the enclosure. The simulations provide a deeper insight into enclosure flows involving electrically conducting nanofluids in advanced processing systems for nanomaterials and hybrid fuel cells utilizing electromagnetic and liquid fuel technologies.
Top advances of the year: Perioperative therapy for lung cancer
Authors: Aredo Jacqueline V. , Wakelee Heather A. 
Published: May 2024

AbstractEmerging data supporting the rise of perioperative immune checkpoint inhibitors (ICIs) as a standard of care in the treatment of early stage, surgically resectable non‐small cell lung cancer (NSCLC) dominated the NSCLC news in 2023. Adjuvant pembrolizumab became the second adjuvant ICI to receive US Food and Drug Administration approval in early 2023 after the 2021 approval of adjuvant atezolizumab and the 2022 approval of neoadjuvant nivolumab with chemotherapy. Subsequently in 2023, multiple phase 3 trials examining perioperative ICIs were positive and demonstrated clinically meaningful outcomes by prolonging event‐free survival, improving pathologic complete response rates, and trending toward improved overall survival in most. Perioperative pembrolizumab became the first ICI to attain US Food and Drug Administration approval in this setting through the KEYNOTE‐671 trial (ClinicalTrials.gov identifier NCT03425643), which also demonstrated a definitive overall survival benefit in the entire study population. However, questions remain regarding patient selection for either approach and how we can optimize biomarkers to determine who needs adjuvant therapy after surgery.