bluuebunny/crossref_metadata_2025 huggingface dataset:
A Descriptive Study of ESG Investing: A Way Towards Sustainability
Authors: Mishra Abhishek , Yadav Mahendra Pal Singh
Published: July 2024

Environmental, social, and governance (ESG) considerations have emerged as critical factors in the investment decision-making of companies and individuals. ESG factors assess the impact of environmental, social, and governance aspects of a company. This paper explores the importance of ESG factors for sustainability, the growing trend toward ESG investing, and the challenges and opportunities associated with ESG integration. The study uses a qualitative research design, using secondary sources such as academic articles, company reports, media reports, and statements of persons of importance. The findings reveal that ESG considerations are crucial for sustainable development, the companies that prioritize ESG factors tend to perform better in the long term, have a lesser cost of capital, better retention rate, and lower litigation risks.
Level of pupils´ map skills in Slovakia
Authors: Fuchs Michael , Čipková Elena , Karolčík Štefan , Husárová Kristína , Pčolová Jana
Published: July 2024

The aim of geographical education is to enhance the level of geographical literacy among pupils, enabling them to acquire, comprehend, analyse, and interpret geographic information so they are able to apply it effectively. One approach to improving this literacy level involves utilizing map skills, through which pupils can read, analyse, interpret map content, and even create maps. This research aimed to assess the level of selected map skills among Slovak pupils at the end of lower secondary education (ISCED 2). A self-constructed research tool was used as the research instrument. Analysis of the acquired data revealed an average level of map skills among the pupils. The highest proficiency was observed in tasks focused on utilizing skills associated with map reading. Conversely, the lowest proficiency was found in tasks requiring the application of skills related to map analysis. The data collected suggest that although pupils at the end of lower secondary education possess skills enabling them to obtain necessary information from a map, they encounter challenges in analysing and subsequently interpreting this information.
Impact of Adolescents Lifestyle Habits and Stress on Oral Disease Symptoms
Authors: Kim Ji-Soo ,   The Korean Society of Oral Health Science
Published: July 2024

Objectives: The The aim of this study was to investigate the prevalence of oral disease symptoms among adolescents, and to examine the relationship between the number of oral disease symptoms and lifestyle habits, sleep, and stress.
Methods: The participants included 30,229 middle school students from grades 1 to 3 and 29,811 high school students from grades 1 to 3.
Results: For both the middle school and high school students, the factors associated with an increase in the number of oral disease symptoms were grade level (higher grades), economic status, alcohol consumption, frequency of cariogenic beverage intake, stress, and sleep.
Conclusions: It was determined that national policies are needed to improve those factors that negatively affect the oral health of adolescents.
Changes in Dental Plaque Index and Satisfaction after Oral Health Education using Video Media: For Implant Patients
Authors: Kim Ran , Yoon Hyunseo , Bae Soo Myoung , Jeong Hyun Ja , Kim Hyejin ,   The Korean Society of Oral Health Science
Published: July 2024

Objectives: By implementing oral health education using video media for implant patients, the goal was to change the subjects' awareness and improve their self-management abilities.
Methods: Oral health education using video media was provided for a total of 9 weeks to implant patients who visited the dentist.
Results: As a result of analyzing the change in the modified O'Leary Index for each session of oral health education using video media, the average value of the O'Leary Index test increased significantly from the beginning to the middle and from the middle to the end.
Conclusions: The effectiveness of oral health education using video has been confirmed, and it will be used as data for expanding oral health education and developing programs.
Продолжительность периодов безопасной эксплуатации зданий и сооружений с железобетонными конструкциями
Authors: ТЕРЕХОВ Иван Александрович , ТРЕКИН Николай Николаевич , КОДЫШ Эмиль Наумович , ШМАКОВ Сергей Дмитриевич
Published: July 2024

Для выявления характерных дефектов железобетонных конструкций, а также установления причин их возникновения были обработаны архивные материалы Центрального научно-исследовательского и проектно-экспериментального института промышленных зданий и сооружений по обследованию объектов, расположенных в зонах с различной интенсивностью нагрузок и воздействий, влияющих на образование и развитие дефектов. База данных включала в себя сведения о результатах обследований множества эксплуатируемых зданий и сооружений с применением железобетонных конструкций. По результатам анализа были установлены зависимости изменения технического состояния зданий и сооружений, получены распределения среднего количества дефектов железобетонных конструкций в зависимости от срока эксплуатации зданий. Рекомендованный государственным стандартом на правила обследования и мониторинга технического состояния зданий и сооружений срок проведения обследований установлен одинаковым как для визуального, так и для детального инструментального обследования (5 и 10 лет). Как показали результаты исследования, целесообразно увеличить периодичность проведения детального инструментального обследования зданий и сооружений до 20 лет.
Стеклоблоки: архитектура и конструктив, реальность и будущее
Authors: ГРАНОВСКИЙ Аркадий Вульфович , ЦЫКАНОВСКИЙ Евгений Юльевич , КАКУША Владимир Анатольевич , КУДРЯВЦЕВ Максим Владимирович
Published: July 2024

Проанализирована область применения стеклоблоков в качестве элементов самонесущих стеновых ограждающих и фасадных конструкций, а также архитектурных фрагментов в зданиях и сооружениях различного назначения. Приведены примеры реализованных проектов и запроектированных общественных зданий (в основном зарубежных) с применением в качестве наружных стен кладки из стеклоблоков на различных растворных смесях. Дано описание экспериментальных исследований фрагментов кладки из стеклоблоков на цементных растворах при различных силовых воздействиях (осевое растяжение, сдвиг, сжатие). Проведены исследования фрагментов стен с использованием модели балки-стенки с четырехточечной конфигурацией нагружения экспериментальных образцов. Установлены расчетные характеристики прочности кладки стен из стеклоблоков при различных видах напряженного состояния кладки. Исследована работа металлических анкерных креплений на вырыв из кладки стен из стеклоблоков. Даны рекомендации по применению стеклоблоков в ограждающих стеновых конструкциях с армированием кладки стальной перфорированной лентой.
Pelatihan Kader Kesehatan untuk Meningkatkan Keterampilan Deteksi Dini Stunting
Authors: Indanah Indanah , Jauhar Muhamad , Kartikasari Fitriana , Kusumawardani Lita Heni
Published: July 2024

ENGLISHThe success of finding new cases of stunting is influenced by the ability of health cadres to carry out early detection. The purpose of the study was to identify the effect of health cadre training on stunting early detection skills. The research design used quasi-experiments with variables, namely health cadre training and stunting early detection skills. The population is all health cadres, and there is a sample of 33 health cadres for each intervention and control group. Sample selection is done using the purposive sampling technique. The study was conducted at two Puskesmas in Kudus Regency in November 2021. The research instrument uses observation sheets. Health cadres attended four sessions over two days with duration of 45 to 60 minutes per session in the form of lectures and demonstrations. Data analysis used Wilcoxon and Mann-Whitney tests. Health cadre training improves stunting early detection skills with p value = 0.000 (p<0.05). Increasing the capacity of health cadres to find new cases of stunting in the community can be done through routine coaching that is integrated with child health service programs in health service facilities. INDONESIAKeberhasilan penemuan kasus baru stunting di masyarakat dipengaruhi oleh kemampuan kader kesehatan dalam melakukan deteksi dini. Tujuan penelitian ini untuk mengidentifikasi pengaruh pelatihan kader kesehatan terhadap keterampilan deteksi dini stunting. Desain penelitian menggunakan quasi eksperimen dengan 2 variabel, yaitu pelatihan kader kesehatan dan keterampilan deteksi dini stunting. Populasi penelitian seluruh kader kesehatan dan sampel 33 kader kesehatan untuk masing-masing kelompok intervensi dan kontrol. Pemilihan sampel menggunakanteknik purposive sampling. Kriteria inklusi berupa kader kesehatan aktif, belum pernah mendapatkan pelatihan serupa, berusia dewasa, pendidikan minimal SD, mampu membaca dan menulis. Penelitian dilakukan di dua Puskesmas di Kabupaten Kudus pada bulan November 2021. Instrumen penelitian menggunakan lembar observasi. Kader kesehatan mengikuti empat sesi selama dua hari dengan durasi 45-60 menit/sesi dalam bentuk ceramah dan demonstrasi. Materi terdiri dari konsep tumbuh kembang, deteksi dini stunting, dan komunikasi informasi edukasi stunting. Analisis data menggunakan uji Wilcoxon dan Mann Whitney. Pelatihan kader kesehatan meningkatkan keterampilan deteksi dini stunting dengan nilai p = 0,000 (p<0,05). Peningkatan kapasitas kader kesehatan dalam menemukan kasus baru stunting di masyarakat dapat dilakukan melalui pembinaan rutin terintegrasi dengan program pelayanan kesehatan anak di fasilitas pelayanan kesehatan.
Analisis Efektivitas dan Potensi Peningkatan Penerimaan Pajak Bumi dan Bangunan terhadap Pendapatan Asli Daerah
Authors: Utomo Rohadi , Rahmaliza Rahmaliza
Published: July 2024

ENGLISHDiversion the transfer of Land and Building Tax management from central to regional taxes is intended to increase Original Regional Income. This research aims to determine the effectiveness of increasing Land and Building Tax revenue for Original Regional Income in Lubuklinggau City, and to analyze of Land and Building Tax management in Lubuklinggau City, especially the potential for revenue originating from Land and Building Tax. To measure the level effectiveness of Land and Building Tax revenue, data analysis of the potential and realization PBB revenue is used, while measuring the potential for increasing Land and Building Tax revenue is done by analyzing the area of potential tax areas, the selling value of tax objects, and calculating the potential based on Land and Building Tax rates with the selling value of taxable tax objects. The results of research show that in 2017-2021, Land and Building Tax revenue's effectiveness level was categorized as ineffective because the percentage of Land and Building Tax revenue realization was <60%. In 2021, the effectiveness value was 39.63%. Meanwhile, the potential for increasing Land and Building Tax revenue is significant. The current realization for 2021 was only 15.9% of the existing Land and Building Tax potential. INDONESIAPengalihan pengelolaan Pajak Bumi Bangunan (PBB) dari pajak pusat ke daerah dimaksudkan untuk meningkatkan Pendapatan Asli Daerah (PAD). Penelitian ini bertujuan untuk mengetahui efektivitas penerimaan PBB Kota Lubuklinggau bagi peningkatan PAD Kota Lubuklinggau, serta untuk menganalisis pengelolaan PBB Kota Lubuklinggau terutama potensi penerimaan yang bersumber dari PBB. Untuk mengukur tingkat efektivitas penerimaan PBB digunakan analisis data potensi dan realisasi penerimaan PBB, sedangkan pengukuran potensi peningkatan penerimaan PBB dilakukan dengan menganalisis luas wilayah potensi pajak, objek pajak nilai jual, dan menghitung besarnya potensi penerimaan PBB berdasarkan tarif PBB dengan nilai jual objek pajak kena pajak. Hasil penelitian menunjukkan bahwa pada tahun 2017-2021, tingkat efektivitas penerimaan PBB dikategorikan tidak efektif karena persentase realisasi penerimaan PBB <60%. Tahun 2021 nilai efektivitas sebesar 39,63%. Sementara itu, potensi peningkatan pendapatan PBB cukup besar namun persentase potensi penerimaan PBB tahun 2021 hanya 15,9% dari potensi PBB yang ada, sehingga PBB di Lubuklinggau belum optimal.
Radio Caledonia: Scottish Nationalism and Nazi Radio Propaganda, 1940–1942
Authors: Smyth Graham
Published: July 2024

In June 1940, from somewhere in Scotland, a radio station named Radio Caledonia began to broadcast Scottish nationalist, anti-government and anti-war propaganda to Britain, on behalf of an organisation called the Scottish Peace Front. Its objective was to bring about Scotland's exit from the war, an end to the capitalist system, and the creation of an independent, socialist Scotland. The speaker and scriptwriter behind Radio Caledonia was Donald Grant, a Scot, since dubbed Scotland's Lord Haw-Haw. But Radio Caledonia was only superficially a Scottish nationalist station. In reality, the Scottish Peace Front was an entirely fictitious group, and Radio Caledonia's programmes were made in and broadcast from Berlin under the direction of Joseph Goebbels, as one element of his propaganda campaign against Britain. Radio Caledonia, like other similar ‘secret stations’ commissioned by Goebbels, was conceived of by the Nazi Propaganda Ministry, and its broadcasts written and produced by British renegades. This paper looks at Grant's background and political beliefs, the Nazi propaganda organisation within which he worked in Berlin, and the broadcast output of Radio Caledonia. It concludes that far from being an authentically nationalist or socialist enterprise, Radio Caledonia was devised by German Nazis and British fascists as a tool to achieve their shared aim of bringing about an end to Britain's involvement in the war.
Biomechanical effects of hemin and sildenafil treatments on the aortic wall of chronic-hypoxic lambs
Authors: Navarrete Álvaro , Inostroza Matías , Utrera Andrés , Bezmalinovic Alejandro , González-Candia Alejandro , Rivera Eugenio , Godoy-Guzmán Carlos , Herrera Emilio A. , García-Herrera Claudio
Published: July 2024

Introduction: Gestation under chronic hypoxia causes pulmonary hypertension, cardiovascular remodeling, and increased aortic stiffness in the offspring. To mitigate the neonatal cardiovascular risk, pharmacological treatments (such as hemin and sildenafil) have been proposed to improve pulmonary vasodilation. However, little is known about the effects of these treatments on the aorta. Therefore, we studied the effect of hemin and sildenafil treatments in the aorta of lambs gestated and raised at highlands, thereby subjected to chronic hypoxia.

Methods: Several biomechanical tests were conducted in the descending thoracic aorta (DTA) and the distal abdominal aorta (DAA), assessing 3 groups of study of hypoxic animals: non-treated (Control) and treated either with hemin or sildenafil. Based on them, the stiffness level has been quantified in both zones, along with the physiological strain in the unloaded aortic duct. Furthermore, a morphological study by histology was conducted in the DTA.

Results: Biomechanical results indicate that treatments trigger an increment of axial pre-stress and circumferential residual stress levels in DTA and DAA of lambs exposed to high-altitude chronic hypoxia, which reveals a vasodilatation improvement along with an anti-hypertensive response under this characteristic environmental condition. In addition, histological findings do not reveal significant differences in either structure or microstructural content.

Discussion: The biomechanics approach emerges as a valuable study perspective, providing insights to explain the physiological mechanisms of vascular function. According to established results, alterations in the function of the aortic wall may not necessarily be explained by morphostructural changes, but rather by the characteristic mechanical state of the microstructural components that are part of the studied tissue. In this sense, the reported biomechanical changes are beneficial in mitigating the adverse effects of hypobaric hypoxia exposure during gestation and early postnatal life.
Discovery and prospects of new heterocyclic Isatin-hydrazide derivative with a novel role as estrogen receptor α degrader in breast cancer cells
Authors: Arif Muhammad Nouman , Sarwar Sadia , Firdous Farhat , Saleem Rahman Shah Zaib , Nadeem Humaira , Alamro Abir Abdullah , Alghamdi Amani Ahmad , Alshammari Atekah Hazza , Farooq Omer , Khan Rashid Ali , Faisal Amir
Published: July 2024

Introduction: Isatin, a heterocycle scaffold, is the backbone of many anticancer drugs and has previously been reported to engage multiple cellular targets and mechanisms, including angiogenesis, cell cycle, checkpoint pathways and multiple kinases. Here, we report that a novel isatin derivative, 5i, degrades estrogen receptor alpha (ERα) in estrogen-dependent breast cancer cells. This effect of the isatin nucleus has not been previously reported. Tamoxifen and fulvestrant represent standard therapy options in estrogen-mediated disease but have their own limitations. Isatin-based triple angiokinase inhibitor BIBF1120 (Nintedanib) and multikinase inhibitor Sunitinib (Sutent) have been approved by the FDA.

Methods: Keeping this in view, we synthesized a series of N'-(1-benzyl-2-oxo-1, 2-dihydro-3H-indol-3-ylidene) hydrazide derivatives and evaluated them in vitro for antiproliferative activities in MCF-7 (ER+) cell line. We further investigated the effect of the most potent compound (5i) on the Erα through Western Blot Analysis. We used in silico pharmacokinetics prediction tools, particularly pkCSM tool, to assess the activity profiles of the compounds.

Results and discussion: Compound 5i showed the best antiproliferative activity (IC50 value; 9.29 ± 0.97 µM) in these cells. Furthermore, 5i downregulated ERα protein levels in a dose-dependent manner in MCF-7. A multifaceted analysis of physicochemical properties through Data Warrior software revealed some prominent drug-like features of the synthesized compounds. The docking studies predicted the binding of ligands (compounds) with the target protein (ERα). Finally, molecular dynamics (MD) simulations indicated stable behavior of the protein-ligand complex between ERα and its ligand 5i. Overall, these results suggest that the new isatin derivative 5i holds promise as a new ERα degrader.
Hyaluronic acid modified indocyanine green nanoparticles: a novel targeted strategy for NIR-II fluorescence lymphatic imaging
Authors: Zhang Haiyan , Wang Xinyu , Zhang Yundong , Ma Jinli , Qi Shaolong , Du Jianshi , Jin Chunxiang
Published: July 2024

The lymphatic system, alongside blood circulation, is crucial for maintaining bodily equilibrium and immune surveillance. Despite its importance, lymphatic imaging techniques lag behind those for blood circulation. Fluorescence imaging, particularly in the near-infrared-II (NIR-II) region, offers promising capabilities with centimeter-scale tissue penetration and micron-scale spatial resolution, sparking interest in visualizing the lymphatic system. Although indocyanine green (ICG) has been approved by the Food and Drug Administration (FDA) for use as a near-infrared-I (NIR-I) region fluorescent dye, its limitations include shallow penetration depth and low signal-to-noise ratio. Research suggests that ICG’s fluorescence emission tail in the second near-infrared window holds potential for high-quality NIR-II imaging. However, challenges like short circulation half-life and concentration-dependent aggregation hinder its wider application. Here we developed HA@ICG nanoparticles (NPs), a superior ICG-based NIR-II fluorescent probe with excellent biocompatibility, prolonging in vivo imaging, and enhancing photostability compared to ICG alone. Leveraging LYVE-1, a prominent lymphatic endothelial cell receptor that binds specifically to hyaluronic acid (HA), our nanoprobes exhibit exceptional performance in targeting lymphatic system imaging. Moreover, our findings demonstrate the capability of HA@ICG NPs for capillary imaging, offering a means to assess local microcirculatory blood supply. These compelling results underscore the promising potential of HA@ICG NPs for achieving high-resolution bioimaging of nanomedicines in the NIR-II window.
A two-stage optimization configuration model for multi-type flexible resource considering spatiotemporal response characteristics
Authors: Liang Yan , Zhou Ming
Published: July 2024

As China gradually transitions towards a low-carbon energy structure, the proportion of grid-connected new energy sources like wind and solar power continues to increase. To ensure the safe and reliable operation of the power system while meeting the capacity planning for future new energy installations, there is a need for flexible resources with corresponding adjustment capabilities in the power system. In response to this situation, this paper presents an optimization model for the allocation of multiple types of flexible resources that takes into account spatiotemporal response characteristics. Firstly, a flexibility evaluation model is developed based on spatial and temporal response characteristics. Flexibility evaluation indices, such as flexibility average deficit and flexibility coverage index, are constructed. These indices are used for screening nodes with inadequate flexibility in the power system and analyzing the flexibility adequacy at various nodes. Next, the adjustment characteristics of multiple types of flexible resources are analyzed, and a model for their adjustment capabilities is established. Finally, by considering constraints based on time flexibility evaluation indices, a two-stage optimization model for flexible resource allocation is constructed. This model leverages the multiscale matching characteristics between flexibility resources and the fluctuation patterns of new energy sources to guide the allocation of flexible resources at nodes with insufficient flexibility. The effectiveness and applicability of the proposed flexible resource allocation method are validated using the IEEE 9-node system.
A semi-analytical fracture high-conductivity location diagnostic method for vertically fractured wells in multilayered reservoirs: field case study
Authors: Zhang Yijun , Wang Wanbin , Ma Dudu , Xia Yun , Wang Ningbo , Cheng Shiqing , Wei Cao
Published: July 2024

Deep multilayered reservoirs are usually developed using multilayered fracturing techniques; however, the non-uniform placement of proppant causes uneven distribution of fracture conductivity. This study introduces a semi-analytical well test model for hydraulically fractured wells in multilayered reservoirs, accounting for varying fracture conductivity within the hydraulic fracture. The model is built upon the point source function, boundary element method, Duhamel theorem, and pressure superposition principle. Verification tests are conducted to ensure calculation accuracy. Sensitivity analysis is performed on key parameters, encompassing the transmissibility factor, storativity factor, fracture extension, and fracture conductivity. The findings indicate that 1) Increased heterogeneity among layers correlates with a more pronounced pressure drop; 2) Poorly-propped fracture conductivity influences the duration of bilinear flow, becoming negligible after linear flow; 3) The model’s applicability extends to other multilayered reservoirs (e.g., carbonate reservoirs) with minor adjustments. Lastly, a case study from Xinjiang oilfield is presented to demonstrate that the proposed method can derive reservoir and fracture properties for each layer individually. This study contributes to a deeper understanding of the potential of pressure data in characterizing multilayered reservoirs.
Assessment of heavy metals and its treatment through phytoremediation in groundwater along River Kabul in district Charsadda
Authors: Khan Shehryar , Kamal Masroor , Noor Shah , Afzal Syes Muhammad
Published: July 2024

Life cannot exist without water. Water scarcity is caused by massive groundwater decline. Water contamination is the most common problem spreading worldwide quicker than ever, along with anthropogenic water scarcity. Since tainted water can harm health, water contamination is also contributing to water scarcity. Heavy metals in drinking water have plagued most Asian, African, and European nations for decades. Studies reveal that heavy metals have caused damage in Pakistan, India, and China. This study detects heavy metals in groundwater and treats them with phytoremediation along the river Kabul in district Charsadda. It also measures pH, EC, TDS, turbidity, fluoride, phosphates, nitrites, and nitrates. All indicators meet the WHO and national environmental quality criteria for drinking water, except for turbidity, which exceeds the limit of ≤5 NTU in four examined regions, reaching a maximum of 9.99 NTU. Chemical parameters were within the standard limits, except for high concentrations of arsenic (As) and cadmium (Cd) in samples from S2 (15.20 μg/L) and S1 (20.50 μg/L) compared to WHO’s 10 and 5 μg/L standards. However, the limit is within EPA Pakistan’s 50 and 100 μg/L standards for drinking water, which Pakistan still follows. Heavy metals can harm health, even at low levels. Since the majority of the study area’s population relies on groundwater for drinking and other needs, heavy metal pollution of the groundwater can cause many ailments. Thus, phytoremediation is increasingly vital to reduce these heavy metals to WHO limits to protect human health and the environment.
Vedolizumab plus basiliximab as second-line therapy for steroid-refractory lower gastrointestinal acute graft-versus-host disease
Authors: Gao Zicheng , Fan Zhiping , Liu Zhi , Ye Xu , Zeng Yunxin , Xuan Li , Huang Fen , Lin Ren , Sun Jing , Liu Qifa , Xu Na
Published: July 2024

Background

Steroid-resistant (SR) lower gastrointestinal (LGI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of vedolizumab in the treatment of SR-LGI acute GVHD (aGVHD) remains uncertain. We aimed to assess the efficacy and safety of vedolizumab combined with basiliximab as second-line therapy for SR-LGI-aGVHD.

Methods

This study aimed to explore the efficacy of vedolizumab combined with basiliximab for SR-LGI-aGVHD. The primary endpoint was the overall response (OR) on day 28. Secondary and safety endpoints included durable OR at day 56, overall survival (OS), chronic GVHD (cGVHD), non-relapse mortality (NRM), failure-free survival (FFS), and adverse events.

Results

Twenty-eight patients with SR-LGI-aGVHD were included. The median time to start of combination therapy after SR-LGI-aGVHD diagnosis was 7 (range, 4–16) days. The overall response rate (ORR) at 28 days was 75.0% (95% CI: 54.8%–88.6%), and 18 achieved a complete response (CR) (64.3%, 95% CI: 44.1%–80.7%). The durable OR at day 56 was 64.3% (95% CI: 44.1%–80.7%). The 100-day, 6-month, and 12-month OS rates for the entire cohort of patients were 60.7% (95% CI: 45.1%–81.8%), 60.7% (95% CI: 45.1%–81.8%), and 47.6% (95% CI: 31.4%–72.1%), respectively. The median failure-free survival was 276 days; (95% CI: 50–not evaluable) 12-month NRM was 42.9% (95% CI: 24.1%–60.3%). The 1-year cumulative incidence of cGVHD was 35.7%. Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections. Nine (32.1%) patients developed cytomegalovirus (CMV) reactivation complicated with bacterial infections (25.0%, CMV infection; 7.1%, CMV viremia). Epstein–Barr virus (EBV) reactivation occurred in five patients (17.9%, 95% CI: 6.8%–37.6%). Only three patients (10.7%, 95% CI: 2.8%–29.4%) in our study developed pseudomembranous colitis.

Conclusions

Vedolizumab plus basiliximab demonstrated efficacy in severe SR-LGI-aGVHD and was well-tolerated. Vedolizumab plus basiliximab may be considered a potential treatment option for patients with LGI-aGVHD.
SARS-CoV-2 anti-RBD and anti-N protein responses are differentially regulated between mother-child pairs: insight from a national study cohort at the Faroe Islands
Authors: Jarlhelt Ida , Hansen Cecilie Bo , Pérez-Alós Laura , Weihe Pál , Petersen Maria Skaalum , Garred Peter
Published: July 2024

Background

Knowledge about SARS-CoV-2 antibody dynamics in neonates and direct comparisons with maternal antibody responses are not well established. This study aimed to characterize and directly compare the maternal and infant antibody response in a national birth cohort from the Faroe Islands.

Methods

The levels of immunoglobulins (Ig) targeting the receptor binding domain (RBD) of the spike protein and the nucleocapsid protein (N protein) of SARS-CoV-2 were investigated in maternal blood and umbilical cord blood from neonates. The study included 537 neonates and 565 mothers from the Faroe Islands, and follow-up samples were collected 12 months after birth. Multiple linear regression models were used to assess associations of maternal parameters with maternal and neonatal Ig levels and pregnancy outcomes.

Results

The finding showed that neonates acquired varying levels of SARS-CoV-2 antibodies through transplacental transfer, and the levels were significantly influenced by the mother’s vaccination and infection status. The study also found that maternal vaccination and the presence of SARS-CoV-2 antibodies targeting spike RBD were associated with gestational age and APGAR scores. Furthermore, the anti-RBD and -N protein-specific antibody response dynamics during 12 months after birth exhibited differences between mothers and children. RBD and N protein responses were maintained at follow-up in the mother’s cohort, while only the N protein response was maintained at follow-up in the children’s cohort.

Conclusion

In conclusion, SARS-CoV-2-specific immune responses in newborns rely on maternal immunity, while the persistence of SARS-CoV-2-specific Igs appears to be differently regulated between mothers and children. The study provides new insights into the dynamics of SARS-CoV-2-specific immune responses in newborns and underscores the nuanced relationship between maternal factors and neonatal humoral responses.
Deaths related to post-COVID in Italy: a national study based on death certificates
Authors: Grippo Francesco , Minelli Giada , Crialesi Roberta , Marchetti Stefano , Pricci Flavia , Onder Graziano
Published: July 2024

Introduction

SARS-CoV-2 infection has been associated with the onset or persistence of symptoms in the long-term after the acute infection is resolved. This condition known as Post-COVID, might be particularly severe and potentially life-threatening. However, little is known on the impact of post-COVID condition on mortality. Aim of the present study is to assess and quantify Post-COVID deaths in Italy in years 2020 and 2021, based on an analysis of death certificates.

Methods

Data from the Italian National Cause of Death Register were analyzed. ICD-10 code U09.9, released by the World Health Organization in September 2020, was used to identify the ‘Post-COVID’ condition. Numbers of post-COVID deaths from October 2020 to December 2021 were analyzed. Rates of post-COVID deaths were calculated for the year 2021.

Results

Between October 2020 and December 2021, 4,752 death certificates reporting post-COVID condition were identified. Of these, 14.9% (n = 706) occurred between October and December 2020 and 85.1% (n = 4,046) in 2021. In 46.0% of post-COVID-related deaths, the underlying cause of death was COVID-19. Other frequent underlying causes were heart disease (14.3% of cases), neoplasms (9.2%), cerebrovascular diseases (6.3%) and Alzheimer’s disease and other dementias (5.5%). The mortality rate related to post-COVID conditions in year 2021 was 5.1 deaths per 100 thousand inhabitants and it increased with increasing age. Men showed a higher mortality rate than women (4.3 deaths per 100 thousand in women and 6.0 deaths per 100 thousand in men).

Discussion

Post-COVID conditions contributed to a substantial number of deaths in Italy. Strategies to identify the population at risk of severe long-term consequences of SARS-CoV-2 infection and interventions aimed at reducing this risk must be developed.
Ultrasound-guided gluteal nerves electrical stimulation to enhance strength and power in individuals with chronic knee pain: a randomized controlled pilot trial
Authors: Sartori Francesco , Fagnani Pedro Luiz Flores , Monne-Guasch Laia , La Cagnina Giovanni , Picañol Javier , Puig-Diví Albert
Published: July 2024

Introduction

Various pathophysiological contexts can be accompanied by weakness, arthrogenic muscle inhibition, and even disability. In this scenario, peripheral nerve stimulation has been studied not only for pain management but also for the improvement of neuromuscular parameters. For this purpose, the use of Transcutaneous Electrical Nerve Stimulation (TENS) has typically been investigated, but recently, the use of ultrasound-guided percutaneous peripheral nerve stimulation (pPNS) has gained popularity. In this regard, electrical stimulation has a predisposition to activate Type II muscle fibers and has been shown to be capable of generating short-term potentiation by increasing calcium sensitivity. However, the evidence of pPNS applied in humans investigating such variables is rather limited.

Objectives

This pilot study aimed to assess the feasibility of the methodology and explore the potential of pPNS in enhancing hip extension performance in individuals suffering from knee pain, comparing it with TENS.

Methods

Twelve participants were divided into pPNS and TENS groups, undergoing pre- and post-intervention assessments of peak concentric power (W), strength (N), execution speed (m/s), and one-repetition maximum (1RM) (kg) estimation. For pPNS, two needles were positioned adjacent to the superior and inferior gluteal nerves under ultrasound guidance. For TENS, electrodes were positioned between the posterosuperior iliac spine and the ischial tuberosity, and halfway between the posterosuperior iliac spine and the greater trochanter. The interventions consisted of 10 stimulations of 10 s at a frequency of 10 Hz with a pulse width of 240 μs, with rest intervals of 10 s between stimulations.

Results

Peripheral nerve stimulation significantly improved concentric power at 30% (p = 0.03) and 50% (p = 0.03) of 1RM, surpassing TENS, which showed minimal changes. No significant strength differences were observed post-intervention in either group.

Conclusion

This work presents evidence where pPNS applied to the gluteal nerves results in an enhanced performance of hip extension at submaximal loads. However, this improvement does not seem to be reflected in short-term changes in the estimation of the 1RM by the force-velocity profile.
The DANIsh VASculitis cohort study: protocol for a national multicenter prospective study including incident and prevalent patients with giant cell arteritis and polymyalgia rheumatica
Authors: Nielsen Berit D. , Kristensen Salome , Donskov Agnete , Terslev Lene , Dreyer Lene Wohlfahrt , Colic Ada , Hetland Merete Lund , Højgaard Pil , Ellingsen Torkell , Hauge Ellen-Margrethe , Chrysidis Stavros , Keller Kresten K.
Published: July 2024

The DANIsh VASculitis cohort study, DANIVAS, is an observational national multicenter study with the overall aim to prospectively collect protocolized clinical data and biobank material from patients with polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) diagnosed and/or followed at Danish rheumatology departments. A long-term key objective is to investigate whether the use of new clinically implemented diagnostic imaging modalities facilitates disease stratification in the GCA-PMR disease spectrum. In particular, we aim to evaluate treatment requirements in GCA patients with and without large-vessel involvement, treatment needs in PMR patients with and without subclinical giant cell arteritis, and the prognostic role of imaging with respect to aneurysm development. Hence, in GCA and PMR, imaging stratification is hypothesized to be able to guide management strategies. With an established infrastructure within rheumatology for clinical studies in Denmark, the infrastructure of the Danish Rheumatologic Biobank, and the possibility to cross-link data with valid nationwide registries, the DANIVAS project holds an exceptional possibility to collect comprehensive real-world data on diagnosis, disease severity, disease duration, treatment effect, complications, and adverse events. In this paper, we present the research protocol for the DANIVAS study.

Clinical trial registration: https://clinicaltrials.gov/, identifier NCT05935709.
Integrating serum pharmacochemistry and network pharmacology to explore potential compounds and mechanisms of Alpiniae oxyphyllae fructus in the treatment of cellular senescence in diabetic kidney disease
Authors: Yan Zijie , Zhang Lin , Kang Yu , Liu Shuman , Li Xiaoyan , Li Lidan , Rui Kai , Xiao Man , Xie Yiqiang
Published: July 2024

Background

Diabetic kidney disease (DKD), one of the microvascular complications in patients with diabetes mellitus, is a common cause of end-stage renal disease. Cellular senescence is believed to be an essential participant in the pathogenesis of DKD. Although there is evidence that Alpiniae oxyphyllae fructus (AOF) can ameliorate DKD progression and organismal senescence, its ability to ameliorate renal cellular senescence in DKD as well as active components and molecular mechanisms remain to be explored.

Purpose

This study aimed to investigate the role of AOF in the treatment of cellular senescence in DKD and to explore its active components and potential molecular mechanisms.

Methods

The pharmacological efficacy of AOF in ameliorating cellular senescence in DKD was assessed by establishing DKD mouse models and HK-2 cells under high glucose stress. UHPLC-QTOF-MS was used to screen the active compounds in AOF, which were used in conjunction with network pharmacology to predict the molecular mechanism of AOF in the treatment of cellular senescence in DKD.

Results

In vivo experiments showed that AOF reduced GLU, mAlb, Scr, BUN, MDA, SOD levels, and ameliorated renal pathological damage and renal cell senescence in DKD mice. In vitro experiments showed that AOF-containing serum improved the decline in HK-2 cell viability and alleviated cellular senescence under high glucose intervention. The results of the UHPLC-QTOF-MS screened 26 active compounds of AOF. The network pharmacological analyses revealed that Cubebin, 2′,6′-dihydroxy-4′-methoxydihydrochalcone, Chalcone base + 3O,1Prenyl, Batatasin IV, and Lucidenolactone were the five core compounds and TP53, SRC, STAT3, PIK3CA, and AKT1 are the five core targets of AOF in the treatment of DKD. Molecular docking simulation results showed that the five core compounds had good binding ability to the five core targets. Western blot validated the network pharmacological prediction results and showed that AOF and AOF-containing serum down-regulate the expression of TP53, and phosphorylation of SRC, STAT3, PIK3CA, and AKT.

Conclusion

Our study shows that AOF may delay the development of cellular senescence in DKD by down-regulating the levels of TP53, and phosphorylation of SRC, STAT3, PIK3CA, and AKT.
Therapeutic potential and action mechanisms of licochalcone B: a mini review
Authors: Shaikh Sibhghatulla , Lee Eun Ju , Ahmad Khurshid , Choi Inho
Published: July 2024

Licochalcone B (LicB), a chalcone derived from Glycyrrhiza uralensis and Glycyrrhiza glabra, has received considerable attention due to its diverse pharmacological properties. Accumulated data indicates that LicB has pharmacological effects that include anti-cancer, hepatoprotective, anti-inflammatory, and neuroprotective properties. The action mechanism of LicB has been linked to several molecular targets, such as phosphoinositide 3-kinase/Akt/mammalian target of rapamycin, p53, nuclear factor-κB, and p38, and the involvements of caspases, apoptosis, mitogen-activated protein kinase-associated inflammatory pathways, and anti-inflammatory nuclear factor erythroid 2–related factor 2 signaling pathways highlight the multifaceted therapeutic potential of LicB. This review systematically updates recent findings regarding the pharmacological effects of LicB, and the mechanistic pathways involved, and highlights the potential use of LicB as a promising lead compound for drug discovery.
Dose–response effects of physical exercise standardized volume on peripheral biomarkers, clinical response, and brain connectivity in Parkinson’s disease: a prospective, observational, cohort study
Authors: Rotondo Rossella , Padua Elvira , Annino Giuseppe , Guescini Michele , Donati-Zeppa Sabrina , Goffredo Michela , Stocchi Vilberto , Stocchi Fabrizio , De Pandis Maria Francesca
Published: July 2024

Background

Exercise has been proposed as the “Universal Prescription for Parkinson’s Disease”; however, the specificity of exercise dose in terms of frequency, intensity, duration, and type to be prescribed remains to be elucidated. The 2018 US updated guidelines and WHO Guidelines on Physical Activity and Sedentary Behavior recommend older adults (> 65+ years) to achieve weekly minimal activity levels, indicating the intensity of aerobic exercise as the metabolic equivalent of task and duration as minutes/week (150–300 min/week at a moderate intensity of 3–5.9 MET- or 75–150 min/week of a vigorous intensity of ≥6 MET). Translating these recommendations to PD patients, the study aimed to assess the dose–response effects of standardized volume of structured exercise, measured as METs-minutes/week (weekly energy expenditure) of two different rehabilitation settings to quantify the change in neurotrophic factors. The exercise-induced benefits between the two rehabilitation settings will be evaluated based on motor and non-motor symptoms, kinematic parameters of gait, cognitive function, quality of life, and cortical activity and brain connectivity.

Methods

METEX-PD is a pilot, prospective, observational, cohort study. The study will enroll consecutively thirty (N = 30) participants with mild-to-moderate Parkinson’s disease diagnosis to be assigned to a non-intensive or intensive rehabilitation group. The non-intensive rehabilitation group will achieve a range of 180–270 METs-min/week (90 min/week of low-intensity aerobic exercise, 2–3 METs), while the intensive rehabilitation group will exercise at 1350–1980 METs-min/week (225 min/week of high-intensity aerobic exercise, 6–8.8 METs). The METEX-PD trial will last 12 weeks, including 4 weeks of aerobic training program and two follow-ups. Assessments will be performed at baseline (T0), at the end of the exercise program (T1—end of the program), and 4- and 8 weeks after the end of the training program (FU-1 and FU-2). The primary outcome is the change from baseline in peripheral blood BDNF levels. Secondary outcomes are differences in peripheral biomarkers, functional-motor assessments, clinical-functional evaluations, and brain imaging.

Conclusion

METEX-PD trial will enable us to estimate the change in BDNF levels and other peripheral biomarkers under precise exercise-induced energy expenditure. The primary results of the METEX-PD study will allow the development of a larger multicenter randomized controlled trial to investigate the molecular pathways inducing the change in selected neurotrophic factors, such as BDNF, IGF-1, or irisin, and the downstream mechanisms of neuroplasticity in PD patients.
Aberrant baseline brain activity and disrupted functional connectivity in patients with vascular cognitive impairment due to cerebral small vessel disease
Authors: Mu Ronghua , Yang Peng , Qin Xiaoyan , Zheng Wei , Li Xin , Huang Bingqin , Zhu Xiqi
Published: July 2024

Objective

This study aims to examine the alterations in aberrant brain activity and network connectivity between individuals with mild and major vascular cognitive impairment (VCI).

Materials and methods

A total of 114 patients with cerebral small vessel disease (CSVD) were included in this study, comprising 61 individuals with mild VCI (mean age, 55.7 ± 6.9 years; male, 42.6%) and 53 cases with major VCI (mean age, 57.6 ± 5.5 years; male, 58.5%). Additionally, 53 age-, gender-, and education-matched healthy subjects were recruited as normal controls (NC) (mean age, 54.9 ± 7.9 years; male, 52.9%). All participants underwent neuropsychological assessments and magnetic resonance imaging scans. One-way analysis of variance was used to compare fractional amplitude of low-frequency fluctuation (fALFF) values among the three groups. Two-sample t-tests were conducted to assess functional connectivity matrices between different groups for each connection. Moreover, mediation analyses were performed to explore the mediating effect of aberrant brain activity on the relationship between cognitive impairment and CSVD total burden.

Results

VCI patients exhibited aberrant brain activity in regions such as the right thalamus (THA_R), right cuneus (CUN_R), left postcentral gyrus (PoCG_L), right postcentral gyrus (PoCG_R), right median cingulate, paracingulate gyri (PCG_R), and left precuneus (PCUN_L). Reduced positive functional connectivity was predominantly observed among nodes including PCUN_L, CUN_R, PoCG_L, PoCG_R, right posterior cingulate (PCG_R), and left occipital gyrus (IOG_L) in VCI patients. The aberrant baseline brain activity and disrupted brain network were more pronounced with worsening cognitive function. Increased fALFF values in THA_R, CUN_R, and PoCG_L mediated cognitive impairment in CSVD patients.

Conclusion

Abnormal brain activities in THA_R, CUN_R, and PoCG_L, along with their associated abnormal functional connections, play a significant role in VCI. The study revealed a progressive increase in aberrant brain activity and network connectivity with advancing stages of VCI.
Association of common genetic variants with chronic axonal polyneuropathy in the general population: a genome-wide association study
Authors: Taams Noor E. , Knol Maria J. , Hanewinckel Rens , Drenthen Judith , Reilly Mary M. , van Doorn Pieter A. , Adams Hieab H. H. , Ikram M. Arfan
Published: July 2024

Introduction

Disease susceptibility of chronic axonal polyneuropathy is not fully explained by clinical risk factors. Therefore, we determined the contribution of common genetic variants in chronic axonal polyneuropathy in the general population.

Methods

This study was performed in two population-based studies. Polyneuropathy diagnosis was based on screening in the Rotterdam Study and on ICD-10 codes in the UK Biobank. We determined the heritability of the sural nerve amplitude and performed genome-wide association studies of chronic axonal polyneuropathy and sural sensory nerve amplitude. Furthermore, we zoomed in on variants in and surrounding 100 autosomal genes known to cause polyneuropathy based on literature and expert knowledge (candidate genes), and we performed a gene-based analysis. Analyses were adjusted for age, sex and population stratification.

Results

Chronic axonal polyneuropathy was present in 2,357 of the 458,567 participants and 54.3% of the total population was female. Heritability of sural nerve amplitude was 0.49 (p = 0.067) (N = 1,153). No variants (p < 5.0×10−8) or genes (p < 2.7×10−6) reached genome-wide significance for its association with polyneuropathy. Focusing on variants in and surrounding the candidate genes in the GWAS (p < 3.9×10−6) and on these genes in the gene-based analysis (p < 5.0×10−4) neither yielded significant results.

Discussion

We did not find common variants associated with chronic axonal polyneuropathy in the general population. Larger studies are needed to determine if genetic susceptibility based on both common and rare genetic variants affect the risk for chronic axonal polyneuropathy in the general population.