bluuebunny/crossref_metadata_2025 huggingface dataset:
20 Years in the European Union in Terms of Law and the Era of Sustainability
Authors: Gazdagová Laura
Published: December 2024

This publication captures the conference proceedings of the international scientific conference "20 years in the European Union in terms of law and the era of sustainability". The conference took place on 3rd September 2024 at the Faculty of Law, Pavol Jozef Šafárik University in Košice, in hybrid form.

The first part of the conference proceedings includes contributions concerning EU law in proceedings before the Constitutional Court of the Slovak Republic with focus to current issues and challenges after 20 years of membership of the Slovak Republic in the EU, European law from the perspective of international constitutionalism in a green coat, the impact of the entry of the Baltic states into the European Union on the question of the nationality of natural persons, the single digital market in the context of the Slovak Republic, the impact of European Union law in the field of personal data protection on the territory of the Slovak Republic, the principle of environmental protection in economic competition and international jurisdiction for private law claims for compensation for damage caused to the environment.

The second part of the conference proceedings includes contributions concerning the process of enshrining human right to environment in international law and European law, the development of biodiversity protection in the EU, NATO´s role in climate change response to meet the sustainability and suing tort damages from the Dieselgate emissions scandal.
PENGARUH EARNINGS PERSISTANCE, DIVIDEND POLICY DAN INVESTMENT POLICY TERHADAP FIRM VALUE
Authors: Wendy Salim Saputra  , Lidya
Published: December 2024

ABSTRAK
Tujuan penelitian ini yaitu untuk melakukan pengujian pengaruh antara earnings persistance, dividend policy dan investment policy terhadap firm value. Metode analisis yang dipergunakan adalah metode statistik dengan jenis penelitian kuantitatif. Pada penelitian ini, untuk memperoleh sampel menggunakan non probability sampling dengan purposive sampling berdasar pada data annual report perusahaan LQ45 yang diakses dari situs Bursa Efek Indonesia dengan tahun pengamatan pada periode 2020-2022. Pada penelitian ini, terdapat 12 perusahaan yang memenuhikriteria sampling dan dipergunakan sebagai sampel. Pengujian data dilakukan dengan software SPSS 25 dengan model analisis regresi berganda. Hasil penelitian mengungkapkan bahwa earnings persistance dan investment policy tidak berpengaruh terhadap firm value, sementara dividend policy berpengaruh terhadap firm value.
Kata Kunci: persistensi laba; kebijakan dividen; kebijakan investasi; nilai perusahaan
PERAN FINANCIAL DISTRESS MEMEDIASI PENGARUH RASIO KEUANGAN TERHADAP NILAI PERUSAHAAN
Authors: Silvia Restycha Dewi  , Anisa Putri
Published: December 2024

ABSTRAK
Penelitian ini bertujuan untuk menganalisis peran financial distress dalam memediasi pengaruh rasio keuangan terhadap nilai perusahaan. Variabel terikat dalam penelitian ini adalah profitabilitas, likuiditas dan solvabilitas, sedangkan variabel bebasnya adalah nilai perusahaan dengan financial distress sebagai variabel intervening. Metode penelitian yang digunakan adalah kausal komparatif dengan menggunakan data sekunder berupa laporan keuangan perusahaan. Sampel dalam penelitian dipilih dengan menggunakan metode purposive sampling, sehingga diperoleh sampel sebanyak 54 dari 18 perusahaan sektor industri yang terdaftar di Bursa Efek Indonesia (BEI) periode 2019-2021. Data diolah menggunakan SPSS versi 26. Hasil pengujian pada penelitian ini menunjukkan bahwa profitabilitas dan financial distress tidak berpengaruh terhadap nilai perusahaan, sedangkan likuiditas dan solvabilitas berpengaruh terhadap nilai perusahaan. Profitabilitas, likuiditas, dan solvabilitas tidak berpengaruh terhadap financial distress. Berdasarkan uji Sobel menunjukkan bahwa financial distress tidak mampu memediasi pengaruh profitabilitas, likuiditas, dan solvabilitas terhadap nilai perusahaan.
Kata Kunci: financial distress, ratio keuangan, profitabilitas, likuiditas, solvensi, nilai perusahaan
Studi Kualitatif: Identifikasi Determinan Audit Report Lag Pada Kantor Akuntan Publik DSI Cabang Surabaya
Authors: Umi Nur Fryda Kusli Rochmah  , Acynthia Ayu Wilasittha
Published: December 2024

Abstrak
 
Penelitian ini bertujuan agar dapat mengidentifikasi determinan serta pencegahan terkait fenomena audit report lag pada Kantor Akuntan Publik (KAP) DSI Cabang Surabaya dengan menggunakan pendekatan kualitatif. Audit report lag merujuk pada selang waktu antar akhir periode akuntansi hingga tanggal diperiliskannya laporan audit yang menjadi indikator penting dari efisiensi serta efektivitas proses audit. Wawancara kepada para auditor KAP Djoko, Sidik & Indra Cabang Surabaya yang berpengalaman dalam menangani kasus audit report lag menjadi sumber data yang primer dari penelitian ini. Melalui wawancara mendalam bersama auditor juga manajer di KAP DSI cabang Surabaya, studi ini mengungkap berbagai macam faktor utama yang berkaitan dengan audit report lag. Hasil penelitian mengindikasikan bahwa kapasitas dan beban kerja auditor, kompleksitas klien, perencanaan juga penjadwalan audit, serta koordinasi bersamaan klien merupakan determinan utama yang berkontribusi ke audit report lag. Dari temuan tersebut, terdapat beberapa saran praktis yang dapat dilakukan oleh auditor untuk meminimalisir audit report lagi antara lain optimalisasi distribusi beban kerja, peningkatan perencanaan juga penjadwalan audit, program pelatihan berkelanjutan, serta perbaikan komunikasi juga koordinasi bersamaan klien.
 
Kata Kunci: Audit Report Lag; Kantor Akuntan Publik; juga Kualitas Audit
Analisis Pengaruh Penerapan Green Accounting, Kinerja Lingkungan Dan Pengungkapan Corporate Social Responsibility Terhadap Return Saham
Authors: Sekar Arum Nurlatifah  , Annafi Indra Tama
Published: December 2024

Abstrak
Studi ini bertujuan untuk memberikan informasi bagi para investor dan manajer perusahaan dalam memahami factor-faktor yang mempengaruhi tingkat pengembalian saham. Kajin ini juga menyoroti pentingnya strategi keberlanjutan dalam meningkatkan daya tarik investasi. Dalam pasar modal, PT Unilever Indonesia Tbk menghadapi penurunan harga saham sebesar 30,95% year-to-date. Untuk menghadapi situasi ini, perusahaan mengambil inisiatif strategi dengan mengedepankan upaya pelestarian ekosistem. Langkah ini diharapkan dapat memperbaiki minat investor dan mengoptimalkan tingkat return saham. Studi ini bertujuan untuk menyelidiki dampak penerapan green accounting, kinerja lingkungan serta pengungkapan corporate social responsibility terhadap retrun saham. Metodologi penelitian ini menggunakan uji asumsi klasik dan analisis regresi unbalanced data menggunakan bantuan software E-Views 12. Data yang dimanfaatkan dalam penelitian ini bersumber dari dokumentasi perusahaan dalam sektor consumer non-cyclical yang tercatat sebagai emiten di pasar modal Indonesia. Sampel sipilih menggunakan teknik purposive sampling mencakup periode 2020-2022, menghasilkan 31 sampel perusahaan sebagai subjek penelitian. Temuan studi ini menemukan bahwa penerapam green accounting dan kinerja lingkungan memiliki pengaru terhadap return saham. sedangkan pengungkapan corporate social responsibility tidak memiliki pengaruh terhadap return saham. 
Kata kunci: green accounting; kinerja lingkungan; csr; return saham;
Muhammed et-Trabzonî el-Medenî’nin Fıkhî Sorulara Cevap Üretme Faaliyeti
Authors: Çil Mustafa
Published: December 2024

Şer‘î ilimler sahasında araştırma yapanların yakın zamanda fark ve iltifat ettiği konu başlıklarından biri de ‘Muhammed et-Trabzonî el-Medenî’dir. Belli eserlerinin tahkik ve incelemesine yoğunlaşmış bu araştırmalar onun hayatına dair malumatı da zenginleştirmiş ve daha vasıflı hâle getirmiştir. Bununla birlikte Trabzonî’nin ilmî düşüncesi bütün veya ilgilendiği ilim dalları özelinde yeterince işlenmiş değildir. Onun fıkıh anlayışı hakkında konuşabilmek için de teliflerinin ve çeşitli şekillerde hizmet ettiği başka birçok eserin incelenmesine ihtiyaç vardır. Trabzonî’nin fıkıh telifleri fürû-i fıkıh alanına münhasır olup ağırlıklı olarak ‘ilmihal’ türü kapsamına dâhil edilebilecek konuları ele almaktadır. Birtakım zâbıtları muhtevi Risâletü’n-nezr ‘kavâid’ türüne yakın durur. Risâle fî savmi yevmi’ş-şek, Risâle fî iskâti’s-salât ve Cevâbü’l-es’ileti’l-letî seelehû min ehli’l-Kars ise Trabzonî’ye bilfiil yöneltilmiş sorular ile bunların cevaplarını içermektedir. Dolayısıyla bir yönüyle ‘fetva’ türündedir. Ancak risâlelerdeki meselelerin tip ve amaç farklılığı cevapları da ‘olur/olmaz’ şeklindeki yaygın iftâ kalıbı dışına taşırmış; nispeten uzun ve delilli biçimde zikrine yol açmıştır. Üretip kullandığı malzeme müellifin iftâ yöntemini tespite katkı bakımından özel önemi haizdir. Bunlarda onun ilmî ve belki kişisel yönlerine dair başka veriler bulunması da dikkate alınmaya değer bir ihtimaldir. Bu çalışmada, bahsi geçen üç risâle, öncelikle biçimsel yönden etraflıca tanıtılmıştır. İçeriklerinin tahliliyle de müellifin fıkhî sorulara yaklaşımı belirlenmek istenmiştir. Ulaşılan sonuçlar ve bazısı ilmî varsayımlara dayalı çıkarımlar -inceleme alanının dar olması nedeniyle- başka araştırmalarla desteklenme veya düzeltilmeye açıktır. Bununla birlikte söz konusu tespitlerin Trabzonî’nin fetva âdâbı ve fıkıh usulü anlayışını kısmen de olsa yansıttığı düşünülmektedir. Çalışmanın genel amacı Trabzonî’nin fıkıh anlayışını belirlemeye yönelik kapsamlı ilmî araştırmalara katkı sağlanmasıdır.
Muhammed et-Trabzonî el-Medenî’nin “el-İthâfâtü’s-seniyye fî’l-ehâdîsi’l-kudsiyye” Adlı Eseri Bağlamında Münâvî ve Süyûtî ile Etkileşimi
Authors: Küçükosman Hasan
Published: December 2024

Son dönem Osmanlı alimlerinden olan ve Süleymaniye Müderrisliği görevinde de bulunan Muhammed et-Trabzonî el-Medenî çok yönlü bir alim olarak kabul edilmektedir. Farklı disiplinlerde pek çok eser ortaya koyan et-Trabzonî’nin hadis alanında da önemli eserleri bulunmaktadır. Ancak bu çalışmalarında ne kadar özgün olduğu incelenmesi gereken bir durumdur. Geçmiş dönemlerde eser telifinin genel karakteristik yapısı sebebiyle pek çok yazar yaşadığı dönemin ihtiyacına binaen önemli kaynakları güncellemek istemiştir. et-Trabzonî de temel alanlarda kendisinden önceki alimlerden istifade etmiş ve belli eserler ortaya koymuştur. Bu konuda özellikle Celâleddîn es-Süyûtî ve Abdürraûf el-Münâvî dikkat çekmektedir. Öyle ki et-Trabzonî hadis alanında te’lif ettiği eserlerden birisi olan el-İthâfâtü’s-seniyye fi’l-ehâdîsi’l-kudsiyye adlı çalışması da bu konuda kendisinden iki asır önce yaşamış el-Münâvî’nin el-İthâfâtü’s-seniyye bi’l-ehâdîs̱i’l-kudsiyye isimli eserine hem şekil hem de içerik bakımından benzerlik göstermektedir. et-Trabzonî eserin isminde dahi yalnızca bir harf değişikliği yapmış, giriş kısmında da hemen hemen aynı cümleler kurmuştur. el-Münâvî harf sırasına göre kudsî hadisleri eserinde sıralarken et-Trabzonî farklı bir tasnifte bulunarak üç bölümde rivayetleri ele almıştır. Başka alimlerden de yararlanmış olmakla beraber hadislerin açıklamalarında genellikle Münâvî’den faydalanan et-Trabzonî’nin çalışması Münâvî’nin eserine göre daha hacimlidir. Bununla beraber et-Trabzonî’nin daha çok istifade ettiği ve eserinde zikrettiği alim es-Süyûtî’dir. Zira rivayetlerin çoğunluğunun Süyûtî’nin eserinde geçtiği bizzat müellif tarafından ifade edilmiştir. Bazı farklılıklar olmakla beraber et-Trabzonî eserini Süyûtî ve Münâvî gibi pek çok alimden yararlanarak oluşturmuştur. Ayrıca eserin sonunda kudsî hadislerin tarifi ve kendisine bağlı hükümler hakkında açıklama yapan et-Trabzonî’nin çalışması belli konularda yeni hale gelmiştir. Çalışmamız bu etkinin boyutlarını ele almakta olup et-Trabzonî ile başta Süyûtî ve Münâvî olmak üzere hadis alimleri ve ilimleri ile etkileşimini ortaya koymayı amaçlamaktadır.
Cell-free supernatant of Lactobacillus gasseri 1A-TV shows a promising activity to eradicate carbapenem-resistant Klebsiella pneumoniae colonization
Authors: Vertillo Aluisio Gaia , Mezzatesta Maria Lina , Cafiso Viviana , Scuderi Renata , Stefani Stefania , Santagati Maria
Published: December 2024

Background

The use of beneficial bacteria like Lactobacillus spp. is a potential innovative approach to fight antibiotic-resistant pathogens. Klebsiella pneumoniae is one of the most concerning multi drug-resistant (MDR) pathogens, and its ability to colonize the human gut is considered to be the main reason for recurrent infections in critically ill patients.

Methods

In this study, Lactobacillus gasseri 1A-TV, already described for its probiotic activity, was characterized at the genomic level. Moreover, its cell-free supernatant (CFS) was tested for antimicrobial activity against extended-spectrum β-lactamase (ESBL)- and carbapenemase (KPC)-producing K. pneumoniae clinical isolates.

Results

Whole-genome sequencing showed that the L. gasseri 1A-TV genome was of 2,018,898 bp in size with 34.9% GC content, containing 1,937 putative protein coding sequences, 55 tRNA, and 4 rRNA detected by RAST and classified in 20 functional groups by Cluster of Orthologous Genes (COG). BAGEL4 (BActeriocin GEnome minimal tooL) and the antiSMASH 7.0 pipeline identified two bacteriocin biosynthetic gene clusters (BBGCs), namely, BBGC1 that comprises two class IIc bacteriocins including gassericin A-like bacteriocin, and BBGC2 carrying the class III bacteriocin helveticin J. Strikingly, 1A-TV CFS inhibited the growth of all K. pneumoniae isolates only after 8 h of incubation, showing a bactericidal effect at 24 h and interfering, even at lower concentrations, with the biofilm production of biofilm-producer strains independently of a bactericidal effect. NMR analysis of CFS identified and quantified several metabolites involved in carbohydrate metabolism and amino acid metabolism, and organic acids like ethanol, lactate, acetate, and succinate. Finally, in vitro assays of 1A-TV showed significant co-aggregation effects against carbapenem-resistant K. pneumoniae, namely, strains 1, 2, 3, and 7.

Conclusions

Our findings highlight the antimicrobial activity of 1A-TV as a probiotic candidate or its CFS as a natural bioproduct active against MDR K. pneumoniae strains, underlining the importance of novel therapeutic strategies for prevention and control of ESBL- and carbapenemase-producing K. pneumoniae colonization.
Her, His, and their journey with endometriosis: a qualitative study
Authors: Shinan-Altman Shiri , Wertheimer Aya , Frankel Bat-El , Hamama-Raz Yaira
Published: December 2024

Background

Endometriosis, impacting roughly 10% of reproductive-age women and girls globally, presents diagnostic challenges that can cause significant delays between symptom onset and medical confirmation. The aim of the current study was to explore the experience of women with endometriosis as well as that of their partners, from pre-diagnosis to diagnosis to post-diagnosis.

Methods

In-depth semi-structured interviews were conducted with 10 couples coping with endometriosis. Each partner was interviewed separately, and each interview was analyzed both individually and as part of a dyad, using the dyadic interview analysis method.

Results

Three main themes emerged: (i) “Relationship in the shadow of uncertainty”: Coping with health symptoms prior to the formal endometriosis diagnosis; (ii) Coping together or alone when receiving the endometriosis diagnosis; and (iii) “The day after the diagnosis”: Moving between adversity and growth.

Conclusions

The study's findings emphasize the importance of viewing the diagnosis from a dyadic perspective and comprehensively – that is, from pre-diagnosis to accepting the formal diagnosis to post-diagnosis. This journey can have a profound impact on both couple members, affecting their day-to-day functioning, communication, emotional and physical intimacy, and fertility.
Identification of SPP1+ macrophages as an immune suppressor in hepatocellular carcinoma using single-cell and bulk transcriptomics
Authors: Jin Han , Kim Woonghee , Yuan Meng , Li Xiangyu , Yang Hong , Li Mengzhen , Shi Mengnan , Turkez Hasan , Uhlen Mathias , Zhang Cheng , Mardinoglu Adil
Published: December 2024

Introduction

Macrophages and T cells play crucial roles in liver physiology, but their functional diversity in hepatocellular carcinoma (HCC) remains largely unknown.

Methods

Two bulk RNA-sequencing (RNA-seq) cohorts for HCC were analyzed using gene co-expression network analysis. Key gene modules and networks were mapped to single-cell RNA-sequencing (scRNA-seq) data of HCC. Cell type fraction of bulk RNA-seq data was estimated by deconvolution approach using single-cell RNA-sequencing data as a reference. Survival analysis was carried out to estimate the prognosis of different immune cell types in bulk RNA-seq cohorts. Cell-cell interaction analysis was performed to identify potential links between immune cell types in HCC.

Results

In this study, we analyzed RNA-seq data from two large-scale HCC cohorts, revealing a major and consensus gene co-expression cluster with significant implications for immunosuppression. Notably, these genes exhibited higher enrichment in liver macrophages than T cells, as confirmed by scRNA-seq data from HCC patients. Integrative analysis of bulk and single-cell RNA-seq data pinpointed SPP1+ macrophages as an unfavorable cell type, while VCAN+ macrophages, C1QA+ macrophages, and CD8+ T cells were associated with a more favorable prognosis for HCC patients. Subsequent scRNA-seq investigations and in vitro experiments elucidated that SPP1, predominantly secreted by SPP1+ macrophages, inhibits CD8+ T cell proliferation. Finally, targeting SPP1 in tumor-associated macrophages through inhibition led to a shift towards a favorable phenotype.

Discussion

This study underpins the potential of SPP1 as a translational target in immunotherapy for HCC.
Case report: Vedolizumab in Oral Crohn’s disease: the downsides of a gut-specific therapy for a multi-site disease
Authors: Harte Molly , Macken John , Zou Lifong , Fortune Farida
Published: December 2024

Introduction

Crohn’s disease (CD) is a chronic inflammatory bowel disease which can affect any area of the gastrointestinal tract, including oral tissues. The complex nature of this disease demands interdisciplinary management, especially when both intestinal and oral manifestations are present.

Case

This report presents the case of a 28-year-old male patient with oral, ileo-caecal and peri-anal CD managed jointly between Gastroenterology and Oral Medicine. Treatment with vedolizumab, an α4β7 integrin with gut-selective anti-inflammatory activity, resulted in excellent ileo-caecal disease control, but was ineffective in controlling oral manifestations. The absence of MAdCAM-1 expression in oral tissues, necessary for vedolizumab’s mechanism, meant that the drug’s anti-inflammatory effects were limited to the gut. This limitation led to worsening oral symptoms, necessitating concomitant azathioprine therapy to manage oral inflammation.

Conclusion

Multidisciplinary collaboration is important when managing CD patients with both oral and gut involvement in CD. Clinicians should be aware that vedoluzimab may be beneficial for intestinal CD, but does not target inflammation in oral tissues due to its gut-specific action. Good knowledge of the pharmacology and mechanism of action of drugs prescribed can aid decision making when prescribing for this group of patients and can limit the need for polypharmacy, often associated with an increased adverse effect profile.
The Janus-faced nature of complement in hemodialysis: interplay between complement, inflammation, and bioincompatibility unveiling a self-amplifying loop contributing to organ damage
Authors: Canaud Bernard , Stenvinkel Peter , Scheiwe Rebecca , Steppan Sonja , Bowry Sudhir , Castellano Giuseppe
Published: December 2024

In hemodialysis (HD), complement activation, bioincompatibility, and inflammation are intricately intertwined. In the 1970s, as HD became a routine therapy, the observation of complement pathway activation and transient leukopenia by cellulosic dialysis membranes triggered the bioincompatibility debate and its clinical relevance. Extensive deliberations have covered definitions, assessment markers, scope, and long-term clinical consequences of membrane-dependent bioincompatibility reactions. While complement pathways’ interplay with coagulation and inflammation has been delineated, HD’s focus has primarily been on developing more biocompatible membranes using advanced technologies. Recent advances and understanding of the current HD delivery mode (4-hour sessions, thrice weekly) suggest that factors beyond membrane characteristics play a significant role, and a more complex, multifactorial picture of bioincompatibility is emerging. Chronic activation of the complement system and persistent low-grade “uremic inflammation” in chronic kidney disease (CKD) and HD lead to premature inflammaging of the kidney, resembling aging in the general population. Cellular senescence, modulated by complement activation and the uremic milieu, contributes to chronic inflammaging. Additionally, the formation of neutrophil extracellular traps (NETs, process of NETosis) during HD and their biological activity in the interdialytic period can lead to dialysis-induced systemic stress. Thus, complement-inflammation manifestations in HD therapies extend beyond traditional membrane-related bioincompatibility consequences. Recent scientific knowledge is reshaping strategies to mitigate detrimental consequences of bioincompatibility, both technologically and in HD therapy delivery modes, to improve dialysis patient outcomes.
Reliability, biological variability, and accuracy of multi-frequency bioelectrical impedance analysis for measuring body composition components
Authors: Looney David P. , Schafer Erica A. , Chapman Christopher L. , Pryor Riana R. , Potter Adam W. , Roberts Brandon M. , Friedl Karl E.
Published: December 2024

Introduction

Bioelectrical impedance analysis (BIA) systems are gaining popularity for use in research and fitness assessments as the technology improves and becomes more affordable and easier to use. Multifrequency BIA (MF-BIA) may improve accuracy and precision using octopolar contacts for segmental analyses.

Purpose

Evaluate reliability, biological variability, and accuracy of component measures (total body water, mass, and composition) of commercially available MF-BIA system (InBody 770, Cerritos, California, USA).

Methods

Fourteen healthy military-age adults were assessed by MF-BIA in duplicate on five laboratory visits across 3 weeks (10 measures each). Participants were evaluated at the same time of day after refraining from strenuous exercise (> 48 h), alcohol consumption (> 24 h), and caffeine, nicotine, and food (> 10 h). Systematic error (test–retest reliability) and biological variability (day-to-day reliability) were summarized by intraclass correlation coefficient (ICC) values determined for body mass (fat, fat-free, total) and body water (extracellular, intracellular, total). Body composition measurements derived from BIA on the second visit were also tested for accuracy compared to dual-energy x-ray absorptiometry (DXA).

Results

Test–retest reliability was very high for all measurements of whole-body water and mass (ICC ≥ 0.999) and high for regional body water and mass (ICC 0.973–1.000). Biological variability was observable with very minor differences between tests (same day) for total and regional body water (0.0–0.2 L) and total and regional body mass measurements (0.0–0.2 kg); while between day differences were slightly higher (0.0–0.5 L and 0.1–0.7 kg). Compared to DXA, the MF-BIA whole-body measures showed an offset in %BF (Bias −4.0 ± 2.8%; Standard error of the estimate (SEE), 2.6%), an overprediction for total body fat-free mass (Bias 2.8 ± 2.1 kg; SEE 2.2 kg) and an underprediction of total body fat mass (Bias −2.9 ± 2.0 kg; SEE 1.9 kg).

Conclusion

Under controlled conditions with fit and healthy men and women, this MF-BIA system has high methodological reliability and demonstrates stable day-to-day measurements of major body composition components. Previously reported ~3% body fat offset compared to criterion methods was again confirmed. Precision of the InBody 770 shows consistency and supports further testing of this specific device as a new military standards method and suitability across a wider range of %BF.
Current state and future prospects of spatial biology in colorectal cancer
Authors: Carranza Francisco G. , Diaz Fernando C. , Ninova Maria , Velazquez-Villarreal Enrique
Published: December 2024

Over the past century, colorectal cancer (CRC) has become one of the most devastating cancers impacting the human population. To gain a deeper understanding of the molecular mechanisms driving this solid tumor, researchers have increasingly turned their attention to the tumor microenvironment (TME). Spatial transcriptomics and proteomics have emerged as a particularly powerful technology for deciphering the complexity of CRC tumors, given that the TME and its spatial organization are critical determinants of disease progression and treatment response. Spatial transcriptomics enables high-resolution mapping of the whole transcriptome. While spatial proteomics maps protein expression and function across tissue sections. Together, they provide a detailed view of the molecular landscape and cellular interactions within the TME. In this review, we delve into recent advances in spatial biology technologies applied to CRC research, highlighting both the methodologies and the challenges associated with their use, such as the substantial tissue heterogeneity characteristic of CRC. We also discuss the limitations of current approaches and the need for novel computational tools to manage and interpret these complex datasets. To conclude, we emphasize the importance of further developing and integrating spatial transcriptomics into CRC precision medicine strategies to enhance therapeutic targeting and improve patient outcomes.
In vitro hair growth-promoting effects of araliadiol via the p38/PPAR-γ signaling pathway in human hair follicle stem cells and dermal papilla cells
Authors: Park Seokmuk , Park Han Woong , Seo Dae Bang , Yoo Dae Sung , Bae Seunghee
Published: December 2024

Background

Scalp hair plays a crucial role in social communication by expressing personal appearance and self-identity. Consequently, hair loss often leads to a perception of unattractiveness, negatively impacting an individual’s life and mental health. Currently, the use of Food and Drug Administration (FDA)-approved drugs for hair loss is associated with several side effects, highlighting the need for identifying new drug candidates, such as plant-derived phytochemicals, to overcome these issues.

Objective

This study investigated the hair growth-promoting effects of araliadiol, a polyacetylene compound found in plants such as Centella asiatica.

Methods

We employed an in vitro model comprising human hair follicle stem cells (HHFSCs) and human dermal papilla cells (HDPCs) to evaluate the hair growth-promoting effects of araliadiol. The proliferation-stimulating effects of araliadiol were assessed using water-soluble tetrazolium salt assay, adenosine triphosphate content assay, and crystal violet staining assay. In addition, we performed luciferase reporter assay, polymerase chain reaction analysis, cell fractionation, Western blot analysis, and enzyme-linked immunosorbent assay (ELISA) to elucidate the mechanism underlying the hair growth-inductive effects of araliadiol.

Results

Araliadiol exhibited both proliferation- and hair growth-promoting effects in HHFSCs and HDPCs. Specifically, it increased the protein expression of cyclin B1 and Ki67. In HHFSCs, it elevated the expression of hair growth-promoting factors, including CD34, vascular endothelial growth factor (VEGF), and angiopoietin-like 4. Similarly, araliadiol increased the expression of hair growth-inductive proteins such as fibroblast growth factor 7, VEGF, noggin, and insulin-like growth factor 1 in HDPCs. Subsequent Western blot analysis and ELISA using inhibitors such as GW9662 and SB202190 confirmed that these hair growth-promoting effects were dependent on the p38/PPAR-γ signaling in both HHFSCs and HDPCs.

Conclusion

Araliadiol promotes hair growth through the p38/PPAR-γ signaling pathway in human hair follicle cells. Therefore, araliadiol can be considered a novel drug candidate for the treatment of alopecia.
Computational studies for pre-evaluation of pharmacological profile of gut microbiota-produced gliclazide metabolites
Authors: Đanić Maja , Pavlović Nebojša , Zaklan Dragana , Stanimirov Bojan , Lazarević Slavica , Al-Salami Hani , Mikov Momir
Published: December 2024

Background

Gliclazide, a second-generation sulfonylurea derivative still widely used as a second-line treatment for type 2 diabetes mellitus, is well known to be subject to interindividual differences in bioavailability, leading to variations in therapeutic responses among patients. Distinct gut microbiota profiles among individuals are one of the most crucial yet commonly overlooked factors contributing to the variable bioavailability of numerous drugs. In light of the shift towards a more patient-centered approach in diabetes treatment, this study aimed to conduct a pharmacoinformatic analysis of gliclazide metabolites produced by gut microbiota and assess their docking potential with the SUR1 receptor to identify compounds with improved pharmacological profiles compared to the parent drug.

Methods

Ten potential gliclazide metabolites produced by the gut microbiota were screened for their pharmacological properties. Molecular docking analysis regarding SUR1 receptor was performed using Molegro Virtual Docker software. Drug-likeness properties were evaluated using DruLiTo software. Subsequently, the physicochemical and pharmacokinetic properties of gliclazide and its metabolites were determined by using VolSurf+ software package.

Results

All studied metabolites exhibited better intrinsic solubility than gliclazide, which is of interest, considering that solubility is a limiting factor for its bioavailability. Based on the values of investigated molecular descriptors, hydroxylated metabolites M1-M6 showed the most pronounced polar and hydrophilic properties, which could significantly contribute to their in vivo solubility. Additionally, docking analysis revealed that four hydroxyl-metabolites (M1, M3, M4, and M5), although having a slightly poorer permeability through the Caco-2 cells compared to gliclazide, showed the highest binding affinity to the SUR1 receptor and exhibited the most suitable pharmacological properties.

Conclusion

In silico study revealed that hydroxylated gut microbiota-produced gliclazide metabolites should be further investigated as potential drug candidates with improved characteristics compared to parent drug. Moreover, their part in the therapeutic effects of gliclazide should be additionally studied in vivo, in order to elucidate the role of gut microbiota in gliclazide pharmacology, namely from the perspective of personalized medicine.
Prefrontal serotonin depletion delays reversal learning and increases theta synchronization of the infralimbic-prelimbic-orbitofrontal prefrontal cortex circuit
Authors: Estrada-Reyes Yoana , Cervantes-Alfaro José Miguel , López-Vázquez Miguel Ángel , Olvera-Cortés María Esther
Published: December 2024

Introduction

Prefrontal serotonin plays a role in the expression of flexible behavior during reversal learning tasks as its depletion delays reversal learning. However, the mechanisms by which serotonin modulates the prefrontal cortex functions during reversal learning remain unclear. Nevertheless, serotonin has been shown to modulate theta activity during spatial learning and memory.

Methods

We evaluated the effects of prefrontal serotonin depletion on theta activity in the prefrontal infralimbic, prelimbic, and orbitofrontal (IL, PL, and OFC) subregions of male rats during a spatial reversal learning task in an aquatic T-maze.

Results

Prefrontal serotonin depletion delayed spatial reversal learning and increased theta activity power in the PL and OFC. Furthermore, animals with serotonin depletion had increased functional coupling between the OFC and the IL and PL cortices compared with the control group.

Discussion

These results indicate that serotonin regulates reversal learning through modulation of prefrontal theta activity by tuning both the power and functional synchronization of the prefrontal subregions.
Menisoxoisoaporphine A, a novel oxoisoaporphine alkaloid from Menispermi Rhizoma, inhibits inflammation by targeting PDE4B
Authors: Qiao Xin , Cao Xiaojuan , Xu Shuang , Wang Cunlin , Guo Rui , Yao Xiaojuan , Zhang Qiong
Published: December 2024

Background

Dysregulated and excessive inflammatory reactions can lead to tissue damage, which is the underlying cause of most human diseases. Menisoxoisoaporphine A (MA), a novel oxoisoaporphine alkaloid, was obtained from Menispermi Rhizoma, a traditional Chinese medicinal herb used in the treatment of inflammatory conditions in clinical practice. This suggests that MA has very promising potential for the development of anti-inflammatory therapeutics. Hence, this study aims to investigate the anti-inflammatory effects and underlying mechanisms of MA.

Method

The anti-inflammatory effects of MA were evaluated in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 cells. Its underlying mechanisms were explored through RNA sequencing and Western blotting. The binding modes and interactions sites between MA and phosphodiesterase 4B (PDE4B) were predicted using molecular docking and validated by molecular dynamics simulation.

Results

MA treatment significantly reduced LPS-induced morphological changes, inflammatory cytokine relesae, and proinflammatory genes expression in RAW264.7 cells compared to the LPS-induced controls. Transcriptome sequencing analysis suggested that PDE4B might be a key target for MA to exert its therapeutic effect. Mechanismly, MA directly acted on Tyr405 site of PDE4B, thus leading to a sustained elevation of the cyclic adenosine monophosphate (cAMP) levels, which subsequently inactivated NF-κB signaling pathway by phosphorylating protein kinase A (PKA). MA inhibited the NF-κB-mediated inflammatory response depending on PDE4B.

Conclusion

MA, a natural and novel compound, exerted anti-inflammatory effects in LPS-induced RAW264.7 macrophage cells. It demonstrated a strong binding ability to the Tyr405 sites of PDE4B, thereby inhibiting NF-κB signaling pathway by regulating the cAMP-PKA axis. Elucidating the interaction between MA and PDE4B holds significant potential for the advancement of innovative therapeutic strategies aimed at inflammatory diseases. By strategically modulating this interaction, it may be feasible to achieve more precise regulation of inflammatory responses, thereby offering promising therapeutic benefits for conditions such as rheumatoid arthritis, asthma, and inflammatory bowel disease.
Cognitive abilities in a sample of young Swedish children
Authors: Clausén Gull Ingela , Stålnacke Johanna , Eninger Lilianne , Ferrer-Wreder Laura , Eichas Kyle
Published: December 2024

Cognitive abilities are closely related to social emotional competences (SEC). These abilities are important foundations in order to adapt to school, interact with peers and adults, as well as to navigate the wider socio-cultural context in which one develops. Further, young children are also acquiring and deepening their language and preliteracy skills which are important for later academic learning. Central to cognitive abilities are the processes that enable deliberate and goal-oriented actions, which fall under the conceptual umbrella of executive functions (EFs). In this study, we applied a conceptually broad perspective to examine cognitive abilities, preliteracy and SEC in preschool aged children. Children were participants in an intervention trial of the preschool edition of Promoting Alternative Thinking Strategies (PATHS®) conducted in preschools located in three municipalities within a large city in Sweden. Pre-test data were used to examine cognitive abilities and SEC in this sample of Swedish 4 to 5-year-old children (N = 247). We first performed an exploratory factor analysis including the wide range of examined abilities, and found that measures of abilities typically viewed as SEC, did not group with measures of preliteracy skills and abilities typically considered as EFs. Second, we performed confirmatory factor analyses on remaining relevant indicators of cognitive abilities, which indicated a two-factor model best fit the data, with one factor involving inhibitory control and one factor involving more complex and high-demanding skills (working memory, cognitive flexibility, and preliteracy skills). Results indicated that more complex EFs and preliteracy skills were closely linked, and can be differentiated from inhibitory control, already in the preschool years. Findings also point to the importance of including a broad range of cognitive abilities (e.g., pre-literacy skills) in order to gain a nuanced description of possible interrelations between cognitive and social emotional development. Furthermore, this study contributes to the theoretical discussion on EF structure during childhood, and provides a sound empirical rationale for the further development of early interventions that consider young children’s executive functions and preliteracy skills.
Relationship between parental involvement and children’s positive mental character during early years: the moderating role of parent-teacher relationship and teacher-parent relationship
Authors: Cai Liman , Huang Peishan , Guo Yuanfang
Published: December 2024

Introduction

To explore the association between parental involvement and children’s positive mental character, and examine the moderating effect of the relationship between teachers and parents.

Methods

The present study conducted latent moderated structural equation model among 167 Chinese preschool teachers and 1019 preschool children and their parents. Parents reported children’s positive mental character and perceived relationships with their children’s teachers while teachers reported their perceived relationships with each child’s parents.

Results

The results indicated that (1) three dimensions of parental involvement (home-based involvement, school-based involvement and home-school conferencing) were positively related to children’s positive mental character; (2) teacher-perceived teacher-parent relationship moderated the association between home-based involvement and children’s positive mental character; (3) the effects of school-based involvement * parent-teacher relationship and home-school conferencing * parent-teacher relationship on children’s positive mental character were significant.

Discussion

This study provided the implications for promoting the development of positive mental character among Chinese preschool children.
A common metric for questionnaires on health anxiety in cancer patients
Authors: Friedrich Michael , Schulte Thomas , Malburg Merle , Hinz Andreas
Published: December 2024

After a cancer diagnosis, life is accompanied by worries, concerns and fears that the disease will recur or worsen. These can be normal and useful reactions but may also become so severe that they interfere with everyday functioning. A challenge for patient care is that the theoretical similarity of these reactions, is not consistently conceptualized in practice, hence the empirical comparability of their measures is unclear. Here we intend to show that the theoretical similarity is also empirically justified, and we present a common metric in graphical form that allows direct comparisons between different questionnaires. A total of 1,733 cancer patients completed the Fear of Progression Questionnaire Short Form, Questionnaire on Stress in Cancer Patients–revised version, Concerns About Recurrence Questionnaire, the subscales Health Distress and Negative Health Outlook of the EORTC QLQ-SURV100, and the Whiteley Index. Using a model based on item response theory, we linked the score values of the individual questionnaires. The main outcome of this study is a diagram that can be used to convert the respective values of eight questionnaires on health anxiety to another. All instruments showed a reliability above 0.75 near the mean health anxiety level. The common metric can be used to compare measurements with these questionnaires in terms of the level of health anxiety. Additionally, the reliability of the instruments can be judged at different levels of anxiety. This allows for a better comparability of test results and facilitates communication about the results among experts and with patients.
Exercise intervention on the brain structure and function of patients with mild cognitive impairment: systematic review based on magnetic resonance imaging studies
Authors: Xu Jing , Yu Jiangsheng , Li Gai , Wang Yanqiu
Published: December 2024

Objective

This systematic review evaluates the impact of exercise intervention in MCI patients and discusses the potential neural mechanisms.

Methods

A systematic search and screening of relevant literature was conducted in English and Chinese databases. Based on predefined keywords and criteria, 24 articles were assessed and analyzed.

Results

Structurally, a significant increase was observed in the hippocampal and gray matter volumes of MCI patients following exercise intervention, with a trend of improvement in cortical thickness and white matter integrity. Functionally, after the exercise intervention, there were significant changes in the local spontaneous brain activity levels, cerebral blood flow, and functional connectivity during rest and memory encoding and retrieval tasks in MCI patients.

Conclusion

Exercise may contribute to delaying neurodegenerative changes in brain structure and function in patients with MCI. However, the underlying neural mechanisms require further research.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023482419.
Antimicrobial resistance profile of Escherichia coli in drinking water from one health perspective in low and middle income countries
Authors: Desye Belay , Woldetsadik Mawugatie Temeselew , Asmare Lakew , Tsega Yawkal , Melak Dagnachew , Endawkie Abel , Daba Chala
Published: December 2024

Introduction

Antimicrobial resistance is a major global public health concern, especially in low-resource settings. In low- and middle-income countries, the existing evidence about antimicrobial resistance in drinking water is inconsistence and not comprehensive. Therefore, this study aimed to estimate the pooled prevalence of antimicrobial resistance profiles of Escherichia coli from drinking water in low- and middle-income countries.

Methods

This study was conducted using comprehensive literature searches using various databases such as PubMed, Scientific Direct, HINARI, and Google Scholar. Data extraction was performed using Microsoft Excel and exported to STATA 14/SE software for analysis. We used the Joanna Briggs Institute’s quality appraisal tool to ensure the quality of the included studies. A random effects model was employed to estimate the pooled prevalence. Publication bias was evaluated using funnel plots and Egger’s regression test. Subgroup and sensitivity analysis were also conducted in this study.

Results

The study found that the pooled prevalence of Escherichia coli isolates in drinking water was 37.94% (95% CI: 26.73–49.13). The prevalence of multidrug resistance was 43.65% (95% CI: 31.15–56.15). Regarding specific antimicrobials, the pooled resistance levels of Escherichia coli were 54.65% (95% CI: 41.35–67.96) against contrimoxazole, followed by 48.64% (95% CI: −3.6–101) against amoxicillin and 48% (95% CI: −18.1–114.2) against cefuroxime.

Conclusion

The findings indicated a significant prevalence of antimicrobial resistance of Escherichia coli isolated from drinking water and its multidrug resistance. To address this issue, it recommends focusing on improving basic hygiene and sanitation practices and enhancing water and wastewater treatment systems.

Systematic review registration

Identifier CRD42024533592.
The bacterial burden of worn face masks—observational research and literature review
Authors: Kisielinski Kai , Wojtasik Barbara , Zalewska Aleksandra , Livermore David M. , Jurczak-Kurek Agata
Published: December 2024

Introduction

Facemasks were widely mandated during the recent SARS-CoV-2 pandemic. Especially the use by the general population is associated with a higher risk of improper handling of the mask and contamination and potential adverse microbiological consequences.

Methods

We investigated and quantified bacterial accumulation in facemasks used by the general population, using 16S rRNA (Sanger Sequencing), culture and biochemical analysis along with Rose Bengal staining. Additionally, a systematic overview of the literature on face mask contamination was undertaken.

Results

We found an average bacterial load of 4.24 × 104 CFU recovered/mask, with a maximum load of 2.85 × 105 CFU. This maximum is 310 times higher than the limit value for contamination of ventilation system outlet surfaces specified by the German standard VDI 6022. Biochemical and molecular identification predominantly found Staphylococcus species (80%), including Staphylococcus aureus, along with endospore-forming Bacillus spp. Literature reports also indicate contamination of masks by bacterial and fungal opportunists of the genera Acinetobacter, Aspergillus, Alternaria, Bacillus, Cadosporium, Candida, Escherichia, Enterobacter, Enterococcus, Klebsiella (including K. pneumoniae), Micrococcus, Microsporum, Mucor, Pseudomonas, Staphylococcus and Streptococcus. Bacterial counts increase linearly with wearing duration.

Discussion

Prolonged use may affect the skin and respiratory microbiomes, promoting consequential eye, skin, oral and airway conditions. These aspects underscore the urgent need for further research and a risk-benefit analysis in respect of mask use, particularly given their unproven efficacy in disrupting the transmission of respiratory viruses and their adverse social consequences.