bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term evolution of the calibration constant on a mobile/field campaign water vapour Raman lidar
Authors: Chazette Patrick , Totems Julien , Laly Frédéric
Published: January 2025

Abstract. Numerous field campaigns have been carried out to quantify the water vapour content of the atmosphere using vibrational Raman lidar technology. Each of them raises the question of calibration methods, in particular the reliability of this calibration over time. We present a study on the stability of the calibration of the WALI lidar developed at Laboratoire des Sciences du Climat et de l’Environnement in France (LSCE), over a period of 7 years (2016–2022) and across several field campaigns. A calibration method is applied that mainly use radiosondes and, in a few cases, airborne meteorological probes. Complementing the previous approaches, we show that ground-based meteorological measurements can be of great interest for lidar calibration under conditions of vertical stability in the lower troposphere and of good knowledge of the lidar overlap function, with full overlap within the planetary boundary layer. We emphasize that these three calibration approaches remain consistent over time. The observation periods considered here allow us to sample a wide range of water vapour contents in the lower troposphere, from 0.5 g kg-1 to more than 10 g kg-1 characteristic of the variabilities expected over the mid-latitudes and even over the Arctic. We observe a variability of more than 10 % in the calibration constant between field experiments conducted with and without laser injection seeding. The root mean square error is between 0.23 and 0.6 g kg-1, mainly due to the atmospheric variability during the calibration. The bias is small, less than 0.08 g kg-1. For all the situations studied, the correlation coefficient remains high, above 0.75. The instrumental error is comparable to the 0.4 g kg-1 recommended by the World Meteorological Organization (WMO). Such a precision requires the use of a significant number of reference profiles and the remaining limitation is due to the uncertainties associated with in situ weather sensors. We note that the use of ground-based measurements does not introduce any more uncertainty in the lidar calibration coefficient than vertical profiles obtained by radiosondes or airborne means. Furthermore, the use of re-analyses can be an interesting option for calibration when there are no operational constraints.
Alienação, tecnicidade e racialidade: por um diálogo entre Frantz Fanon e Gilbert Simondon
Authors: Gonzaga Gabriel dos Santos
Published: January 2025

Diante do crescimento nos últimos anos dos estudos sobre raça e racismo na área de Ciência, Tecnologia e Sociedade (CTS), além da relevância do tema para o ativismo antirracista, este trabalho visa intervir e contribuir com o campo reconstruindo suas filiações teóricas e metodológicas. Sem pretender exaurir as pesquisas disponíveis nesse recorte, enfatizamos as ramificações antropológicas e sociológicas nos estudos em CTS sobre raça. A partir disso, demonstramos suas matrizes na obra de Frantz Fanon. Por fim, sugerimos que a abordagem fanoniana da intersecção entre raça e tecnologia, fundada no contexto histórico das lutas anticoloniais, pode ser reelaborada diante das transformações apresentadas pelas relações técnicas do digital. Como síntese deste estudo, propomos que novos diálogos com a Filosofia da Técnica, em especial pelo renovado interesse na obra de Gilbert Simondon, oferecem oportunidades de trabalho e reflexão.
Evaluation of XRCC2 Expression in Breast Cancer
Authors: Gilani Naser , Ozaslan Mehmet
Published: January 2025

Breast cancer (BC) is a leading cause of mortality among women worldwide. The X-ray repair cross-complementing group 2 (XRCC2) gene is implicated in DNA repair processes, and its role in BC remains controversial. This study aimed to analyze XRCC2 mRNA expression in BC tissues compared to normal breast tissues to elucidate its potential role in BC pathogenesis. An observational analytical study with a case-control design was conducted at Zheen International Hospital, Erbil, Iraq, from 2021 to 2024. The study included 44 adult women diagnosed with BC, and XRCC2 mRNA levels were measured using real-time quantitative reverse transcription PCR (qRT-PCR). RNA was extracted, converted to cDNA, and analyzed by qRT-PCR. The XRCC2 mRNA expression levels were normalized using GAPDH and statistically analyzed using the 2−ΔCt method. The study found a significant upregulation of XRCC2 expression in BC tissues compared with normal controls (p<0.05), especially in patients aged 40-55 years and those > 56 years (p=0.0392 and p=0.0191, respectively), and in higher BC grades II and III (p=0.0013 and p=0.0051, respectively). Invasive ductal carcinoma exhibited a notable increase in XRCC2 expression (p=0.0006). In conclusion, the increased XRCC2 mRNA expression in BC tissues suggests a possible oncogenic role of XRCC2 in BC development. The correlation between age and cancer grade indicates its potential as a marker for BC progression.
Analisis Perbandingan Kepuasan Mahasiswa Administrasi Negara Universitas Tidar terhadap fasilitas dan pelayanan Gedung Potrobangsan dan Gedung Sidotopo
Authors: Hanifah Eka R.  , Rizka Idfi Kusumaresti  , Ibrahim Kholilulloh
Published: January 2025

Penelitian ini bertujuan untuk mengetahui rasa kepuasaan dari mahasiswa Fakultas Ilmu Sosial dan Ilmu Politik Universitas Tidar dalam pelaksanaan fasilitas yang ada di Gedung Lama (Potrobangsan) dan Gedung Baru (Sidotopo). Secara garis besar dan kasat mata fasilitas yang ada di gedung baru lebih lengkap, namun hal tersebut apakah mampu Fisipi memberikan pelayanan yang prima dan mahasiswa sebagai konsumen dapat merasakan puas akan pelayanan dan fasilitas yang disediakan. Data yang didapatkan dalam penelitian ini berasal dari pengamatan para peneliti dilapangan dan hasil wawancara pada Kepala Tata Usaha Fakultas Ilmu Sosial dan Ilmu Politik. Sasaran penelitian ini kepada mahasiswa Fisip yang telah menggunakan dan merasakan pelayanan Gedung Lama dan Gedung Baru yaitu mahasiswa semester 3 keatas. Hasil penelitian ini menunjukan bahwa rasa kepuasaan mahasiswa akan pelayanan dan fasiilitas yang disediakan di gedung lama dan gedung baru lebih puas terhadap gedung baru. Walaupun terdapat beberapa keluhan lingkungan sekitar yang belum mendukung seperti tempat umum rumah makan yang terbilang masih sedikit di gedung baru dan mobilisasi aktivitasnya yang belum seramai di gedung lama..
Relationship between physical activity and harmful habits in students of human medicine at a peruvian university
Authors: Vásquez Ríos Yordan José , Vallejos Julon Juan Diego , Tejada Montenegro Bryan Artur , Bazualdo-Fiorini Enzo , Portilla-Delgado Esperanza , Barrera-Benavides Luis Gonzalo
Published: January 2025

Objective: Determine the relationship between the level of physical activity and harmful habits of medical students at a Peruvian university in 2024.
Material and methods: 117 students were taken from a population of 210 basic science students from the medical school. To which the IPAQ (Level of physical activity), AUDIT (Risk of alcohol consumption) and Fagerström Test (Tobacco dependence) questionnaires were applied. The SPSS v.29.0.2.0 program was used in data analysis (20); Descriptive and correlational statistics were applied using Pearson's Chi2.
Results: A significant relationship was found between physical activity and alcohol consumption (p=0.004), no significant relationship was found between the level of physical activity and tobacco dependence (p=0.639), 52.1%. of those surveyed have a moderate level of physical activity. 68.4% of those surveyed have a low risk of alcohol consumption and 83.7% of those surveyed do not have the habit of smoking. Sex and year of study were statistically related to alcohol consumption, with p values of <0.001 and 0.03 respectively. There were no personal factors such as age, sex and year of study that were significantly related to tobacco consumption.
Conclusion: There was only a relationship between physical activity and alcohol consumption
Analysis of the institutional strategic plan to improve the quality of life of the inhabitants of a district of Arequipa
Authors: Romero-Carazas Rafael , Fernández-Collado Yaneth , Lazo-Barreda Alfredo Giovanni , Vela-Quico David Fidel , Enciso-Miranda Fernando Ubaldo
Published: January 2025

This paper analyses the Institutional Strategic Plan (PEI) 2024-2027 of the District Municipality of José Luis Bustamante y Rivero, aimed at improving the quality of life of its inhabitants through the implementation of strategic objectives in key areas such as citizen security, environmental management, social development, economic growth and institutional strengthening. The PEI seeks to align municipal actions with national and regional policies, promoting efficient and participatory management. Through a descriptive and non-experimental approach, the strategic objectives of the PEI were analysed, broken down into actions and goals that are monitored through quantifiable indicators. The results of the analysis show progress in the implementation of security policies, with an increase from 92% to 96% in the projected citizen security plan for 2027. Improvements in environmental management are also observed, with an increase in the proper disposal of solid waste and the creation of more green areas. In the social sphere, an increase in the number of beneficiaries of social and cultural programmes is projected, while in institutional management, administrative modernisation and staff training will be strengthened, with an increase from 20% to 30% of staff trained. The analysis of the results highlights the coherence between the objectives of the PEI and the needs of the district, although it identifies areas for improvement in disaster risk management and citizen participation. Finally, it is concluded that the PEI 2024-2027 is a comprehensive tool that, through clear goals and rigorous monitoring, has the potential to generate a positive impact on the sustainable development of the district, with recommendations aimed at strengthening citizen participation and improving evaluation mechanisms.
Emerging and re-emerging diseases in Venezuela as a consequence of climate change. A Systematic Review
Authors: Paz-Gañan Carlos , Aguiar Henry , Coronado Hilfel , Escalona Evelin , Quintana Juan
Published: January 2025

Climate change has affected the biology of vectors and intermediate hosts, increasing the risk of disease transmission, altering the habitat and behavior of poisonous animals, with the consequent modification of their epidemiological patterns; In addition to exacerbating noncommunicable diseases. The objective of this review was to analyze the scientific evidence published, between January 2014 and July 2023, in the different databases on the impact of climate change on the appearance of emerging or re-emerging diseases in Venezuela. The initial search retrieved 925 records, of which only 11 titles met the inclusion criteria. The year 2021 is the one that presents the largest production of publications representing three investigations. Being able to identify a group of re-emerging diseases which are closely related to climate change. Being Dengue, Chagas, Leishmaniasis and Malaria, the most cited.
Frequency and factors associated with oral Candida growth in patients with chronic kidney disease
Authors: Gonzales Cintia Belén , Brusca María Isabel , Garzon María Laura , Vela Ferreira Atilio , Jewtuchowicz Virginia
Published: January 2025

Introduction: Yeasts of the genus Candida, especially Candida albicans, are responsible for oral infections, particularly in immunocompromised individuals. Candida colonization can lead to oral candidiasis and, in severe cases, to esophageal or systemic candidiasis. In patients with chronic kidney disease (CKD), dialysis and immunosuppression increase the risk of oral infections, such as candidiasis.  CKD is a highly prevalent pathology, and patients undergoing peritoneal dialysis are more prone to suffer oral complications due to alterations in oral health habits and defense mechanisms. Objective: To relate risk factors and clinical characteristics of patients with chronic kidney disease to the frequency of oral Candida.Methods: This study is framed within a cross-sectional and analytical design, including a total of 21 patients over 18 years of age who were undergoing peritoneal dialysis treatment at the HIGA “Presidente Perón”. Samples of biofilm from the gingival sulcus and buccal mucosa were collected from each participant using standardized sampling techniques.Results: A predominance of C. albicans (46%) and C. parapsilosis (40%) was observed. The variables that showed a statistically significant association (p < 0.05) were: age (p = 0.002), smoking (p = 0.032), time on peritoneal dialysis (p = 0.005), oral hygiene (p = 0.003), oral health (p = 0.003) and maximum probing depth (p = 0.011).Conclusions: We were able to demonstrate a relationship between oral Candida and CKD, in addition to its association with various risk factors. C. albicans and C. parapsilosis species were the most frequent, especially in women and smokers with prolonged peritoneal dialysis treatment.
Trump, DEI and Culture – what’s the vibe shift?
Authors: Curry Stephen
Published: January 2025

There is an air of defeatism in progressive circles today, the day Donald Trump will be sworn in for a second term as President of the United States of America.
Effectiveness of Student-Facilitated Problem-Based Learning in Integrated Basic Medical Sciences: A Retrospective Quantitative Analysis
Authors: Joshi Lok Raj , Nembang Penchha , Hamal Deependra , Thakur Chandan Kumar , Anu Anuraj , Jha Jay Prakash , Amgain Kapil
Published: January 2025

IntroductionProblem-based learning (PBL) is considered as a historic innovation in medical education. However, shortage of experienced faculty tutors for PBL is a major challenge in resource-limited settings. We aimed to assess effectiveness of student-facilitated PBL in content knowledge at a medical college of Nepal.
MethodsThe Student-facilitated PBL modules were implemented for preclinical medical students in Karnali Academy of Health Science, Jumla during March and April 2024. Our retrospective observational study used both quantitative and qualitative approaches to analyze the outcome and experience of the PBL modules. This article reports the quantitative analysis (with qualitative analysis in a separate paper) which compared pretest and posttest results of the students on multiple-choice questions to assess content knowledge. The maximum possible score was 30 for each test and pass score was set as per modified Angoff method.
ResultsPretest and posttest results of 53 medical students were analyzed. The  results showed that 39 (74%) students passed the pretest and 48 (91%) passed the posttest. This improvement was statistically significant (McNemar's chi-squared=4.27, p=0.04).  The median (interquartile range) of the pretest scores was 19(17-21) and that of the posttest scores was 23(21-25) with a significant increase after the PBL module (Wilcoxon signed rank test, p<0.001, effect size=0.67). The posttest scores of the first year students were comparable to the posttest scores of the second year students (Wilcoxon rank sum test, p=0.40). 
ConclusionThe student-facilitated PBL module was effective for improving content knowledge.
Dans l'œil de l'Obvia - Améliorer la transparence algorithmique grâce aux registres publics
Authors:   Observatoire international sur les impacts sociétaux de l’IA et du numérique
Published: January 2025

Cette note de breffage présente le concept de transparence algorithmique, qui découle du principe plus large de transparence, et recommande le déploiement de registres publics des algorithmes utilisés par l’État comme principal instrument de transparence algorithmique.
Enhancing Hybrid Course Recommendation with Weighted Voting Ensemble Learning
Authors: San Kyawt Kyawt , Win Hlaing Hlaing , Chaw Khin Ei Ei
Published: January 2025

Course recommendation aims to find suitable and attractive courses for students based on their needs, playing a significant role in the curricula-variable system. However, with the abundant available courses, students often face cognitive overload when selecting the most appropriate ones. This research proposes a course recommendation system called the Enhanced Hybrid Course Recommender to address this challenge. This system uses an ensemble learning approach to combine and leverage the power of multiple machine learning classifiers, including Random Forest, Naive Bayes, and Support Vector Machine. By utilizing TF-IDF vectorization for text data transformation and label encoding for target label compatibility, this experiment significantly enhances recommendation precision and relevance, easing students' decision-making process and improving the overall quality of course recommendations. A hybrid approach is applied to improve the recommendation quality by combining predictions from all three classifiers through weighted voting. This ensemble method improves overall robustness and accuracy. This approach not only mitigates the cognitive overload faced by students but also significantly improves the quality of recommendations. Our hybrid model represents a substantial advancement in personalized course recommendation technology by demonstrating superior performance across key evaluation metrics such as accuracy, precision, recall, F1-score, ARHR, and NDCG.
The Digital Transformation of Traditional Culinary Businesses Towards Online Success
Authors: Hakim Andy
Published: January 2025

The digital transformation of traditional culinary businesses has become a critical pathway for achieving sustainable growth and competitiveness in the digital age. This study explores how these businesses transition to online platforms, the challenges they face, and the benefits they achieve. A mixed-methods approach was employed, combining qualitative interviews with traditional culinary business owners and quantitative analysis of business performance data before and after digital adoption. The study also examined case studies of businesses successfully utilizing digital tools such as food delivery platforms, social media marketing, and AI-based analytics. Findings reveal that businesses adopting digital tools experience significant growth in revenue (up to 40%) from 2019-2024, improved operational efficiency, and enhanced customer engagement. However, challenges such as a lack of digital literacy and initial investment costs remain substantial barriers. Successful case studies demonstrate that leveraging partnerships with delivery platforms and effective social media marketing are key strategies for success. Digital transformation provides opportunities to widen market reach, preserve culinary heritage, and enhance customer experiences. To overcome barriers, governments and private organizations can play a role by offering training programs and financial support. The integration of advanced technologies like AI and data analytics also shows promise in driving efficiency and personalization. The digital transformation of traditional culinary businesses is not merely a trend but a necessity for long-term success. Despite challenges, the benefits of increased visibility, operational improvements, and customer satisfaction outweigh the costs, making digital adoption a viable strategy for traditional culinary enterprises.
Pengaruh Gaya Kepemimpinan Dan Kecerdasan Emosional Terhadap Kinerja Karyawan PT Meyer Proteindo Prakarsa
Authors: Syakila Azka  , Ida Farida Syarifah
Published: January 2025

Penelitian ini bertujuan untuk mengetahui adanya keterkaitan, pengaruh atau seberapa besarkah pengaruh antara variabel Gaya Kepemimpinan dan Kecerdasan Emosional secara parsial dan simultan terhadap kinerja karyawan di PT Meyer Proteindo Prakarsa Cipondoh Tangerang. Metode yang digunakan adalah metode kuantitatif, dimana teknik pengumpulan data yang digunakan dengan penyebaran kuesioner, observasi dan data Pustaka. Menggunakan metode sampel jenuh dengan jumlah reponden 60 orang. Dari hasil pengolahan data menggunakan SPSS 24, didapati hasil bahwa Adjusted R Square sebesar 74%. Yang bisa diartikan bahwa variabel Gaya Kepemimpinan dan Kecerdasan Emosional dapat menjelaskan variabel Kinerja sebesar 74%. Dan selisihnya disebabkan variabel lain yang tidak digunakan dalam penelitian ini. Maka, dari penelitian ini menyimpulkan bahwa secara parsial, variabel Gaya Kepemimpinan dan Kecerdasan Emosional berpengaruh secara signifikan terhadap kinerja karyawan PT Meyer Proteindo Pratama. Secara simultan Gaya Kepemimpinan dan Kecerdasan Emosional berpengaruh terhadap Kinerja Karyawan, hasil ini dinyatakan dari pengaruh Gaya Kepemimpinan uji parsial (uji t) pada variabel Gaya Kepemimpinan dimana hasil thitung>ttabel yaitu sebesar 6,668 > 2,002 dengan taraf signifikansi 0,000>0,005. Kecerdasan Emosional juga berpengaruh secara positif dan signifikan terhadap kinerja, hal ini dibuktikan dengan hasil uji parsial dimana hasil thitung>ttabel yaitu sebesar 8,388 > 2,002 dengan taraf signifikansi 0,00 < 0,05. Sedangkan Gaya Kepemimpinan dan Kecerdasan Emosional berpengaruh secara simultan memiliki pengaruh positif dan signifikan, hal ini terbukti dari hasil uji simultan (uji F) dimana hasil fhitung>ftabel yaitu sebesar 80,945 > 3,160 dan taraf signifikasi 0,00 < 0,05.
Avances contemporáneos en la mejora genética bovina frente a los desafíos y perspectivas en el sector zootécnico
Authors: Montero-de-la-Cueva José Vicente
Published: January 2025

The article examines advances in bovine genetic improvement, highlighting its challenges and opportunities for the sustainability and competitiveness of the livestock sector. Although technologies such as CRISPR/Cas9 have revolutionized genetic improvement, their adoption faces economic and technological constraints, especially in regions with limited resources. In addition, intensive selection has reduced genetic diversity, compromising the ability of cattle populations to adapt to disease and climatic changes. Opportunities include genetic conservation programs, germplasm banks and strategic crossbreeding between complementary breeds. Emerging technologies to improve production efficiency and reduce environmental impact are also highlighted. Producer training and inclusive public policies are essential to close the technological gap, guarantee access to these innovations and promote sustainable production systems. In conclusion, overcoming the current challenges requires a multidimensional approach that combines technological advances, biodiversity conservation and institutional support, ensuring efficient and resilient cattle production in the face of global challenges.
The protective action of a novel Dinb protease against diarrhea infection in Drosophila Melanogaster
Authors: Guleria Jyoti , Khan Mohammad Rashid , Khan Minhaj Ahmad
Published: January 2025

The compounds of natural origin prevail to be of great importance in the identification of novel bioactive molecules and are less pernicious towards the ecosystem. Dinb family proteases of Bacillus species possess antimicrobial properties and are reported to inhibit the growth of many pathogenic bacteria, our study also focused on corroborating these effects. Five-day-old Drosophila melanogaster was exposed to Salmonella enterica for up to 96 hours. Once the disease was induced in flies they were shifted to the treatment vials containing 2 mg–10 mg of purified protease. The application of a 23.4 kDa purified protease improved the health of D. melanogaster when compared to the positive control. The protease treatment on the infected flies showed significant stability in cell survival (69%) as well as restoring normal cell functioning. The results indicated that purified protease extended fly life span, restored their locomotive (96.6%), and reproductive ability (38%–67.5%), and reduced oxidative stress in D. melanogaster. The study verified, the protease to be bactericidal against diarrhea pathogens and the significant recovery of the host immune system. Furthermore, the protein can be used to study host-pathogen immune interactions at the cellular level, followed by its testing against a variety of pathogens to explore its broad-spectrum application.
Clinical Outcomes for Uptitration of Baricitinib Therapy in Patients With Severe Alopecia Areata
Authors: Ko Justin M. , Mayo Tiffany T. , Bergfeld Wilma F. , Dutronc Yves , Yu Guanglei , Ball Susan G. , Somani Najwa , Craiglow Brittany G.
Published: August 2023

Importance

Baricitinib is an oral selective Janus kinase 1/2 inhibitor that has achieved clinically meaningful outcomes for scalp, eyebrow, and eyelash hair regrowth in patients with severe alopecia areata (AA) at week 36 of treatment. Treatment with baricitinib, 4 mg, has resulted in higher response rates than baricitinib, 2 mg, at weeks 36 and 52.

Objective

To determine the efficacy of uptitration to baricitinib, 4 mg, for 24 weeks in patients who had previously not responded to baricitinib, 2 mg (Severity of Alopecia Tool [SALT] score of >20).

Design, Setting, and Participants

BRAVE-AA1 and BRAVE-AA2 are multicenter, placebo-controlled, phase 3 randomized clinical trials that were initiated on September 24, 2018, and July 8, 2019, respectively, with follow-up to 200 weeks (data cutoffs of November 11, 2021, and November 5, 2021, respectively). This pooled analysis reports long-term extension data up to week 76. At baseline, 1200 adult patients with severe AA (SALT score ≥50) were randomly assigned in a 3:2:2 ratio to receive baricitinib, 4 mg; baricitinib, 2 mg; or placebo. Patients treated with baricitinib remained on the same treatment dose until week 52. Patients were considered nonresponders to baricitinib, 2 mg, if they had a SALT score greater than 20 after 52 weeks of therapy.

Main Outcomes and Measures

The proportions of patients achieving a SALT score of 20 or lower and clinician-reported outcome for eyebrow hair loss and eyelash hair loss scores of 0 or 1 (full coverage or minimal gaps) with 2-point or higher improvements from baseline (among those with baseline scores ≥2 [significant gaps to no notable hair]) were analyzed through week 76.

Results

At week 52, of the 340 patients (mean [SD] age, 38.4 [12.9] years; 212 [62.4%] female) treated with baricitinib, 2 mg, 212 (62.4%) had a SALT score higher than 20 and were uptitrated to baricitinib, 4 mg. Two-thirds of these patients (142 of 212 [67.0%]) had a baseline SALT score of 95 to 100, indicating very severe AA. At week 76, 55 of the 212 patients (25.9%) had achieved a SALT score of 20 or lower. During the same period, response rates for clinician-reported outcome scores of 0 or 1 increased from 19.3% (31 of 161 patients) to 37.9% (61 of 161 patients) for eyebrows and from 24.1% (33 of 137 patients) to 40.9% (56 of 137 patients) for eyelashes.

Conclusions and Relevance

In this pooled analysis of the BRAVE-AA1 and BRAVE-AA2 trials, uptitration of baricitinib, 2 mg, to baricitinib, 4 mg, in those who did not respond to the 2-mg dose resulted in meaningful improvement of response rates over the subsequent 24 weeks for scalp, eyebrow, and eyelash hair loss.

Trial Registration

ClinicalTrials.gov Identifiers: NCT03570749 and NCT03899259
Modulation of Neuroimmune and Epithelial Dysregulation in Patients With Moderate to Severe Prurigo Nodularis Treated With Nemolizumab
Authors: Deng Junwen , Liao Viviane , Parthasarathy Varsha , Cornman Hannah L. , Kambala Anusha , Kwatra Madan M. , Ständer Sonja , Piketty Christophe , Chaskar Prasad , Krishnaswamy Jayendra Kumar , Julia Valerie , Kwatra Shawn G.
Published: August 2023

Importance

Prurigo nodularis (PN) is a debilitating skin disease characterized by intense pruritus and hyperkeratotic skin nodules. Nemolizumab, a monoclonal antibody targeting interleukin 31 receptor α, is a promising novel therapy for the treatment of moderate to severe PN. The biological mechanisms by which nemolizumab promotes improvement of itch and skin lesions in PN are unknown.

Objective

To characterize changes in plasma protein biomarkers associated with clinical response to nemolizumab in patients with PN.

Design, Setting, and Participants

This multicenter cohort study included patients recruited from Austria, France, Germany, Poland, and the US from a phase 2 clinical trial. Adults diagnosed with moderate to severe PN with severe pruritus for at least 6 months were included in the original trial. Patients in the nemolizumab group were included in the present study if they achieved at least a 4-point decrease in the Peak Pruritus Numerical Rating Scale (PP-NRS) from baseline to week 12 during nemolizumab treatment. Placebo controls did not experience a 4-point decrease in PP-NRS. Mass spectrometry with tandem mass tags to enrich skin-specific protein detection was used to characterize changes in plasma protein expression in nemolizumab and placebo groups. Data were collected from November 2, 2017, to September 26, 2018, and analyzed from December 6, 2019, to April 8, 2022.

Intervention

As part of the clinical trial, patients were treated with 3 doses of nemolizumab or placebo at 0, 4, and 8 weeks.

Main Outcomes and Measures

Changes in plasma and epidermal protein expression in nemolizumab-treated patients compared with the placebo group at 0, 4, and 12 weeks.

Results

Among the 38 patients included in the analysis (22 women and 16 men; mean [SD] age, 55.8 [15.8] years), enrichment analysis of canonical pathways, biological functions, and upstream regulators showed downregulation of terms involving inflammation (IL-6, acute-phase response, signal transducer and activator of transcription 3, and interferon γ), neural processes (synaptogenesis signaling and neuritogenesis), tissue remodeling and fibrosis (transforming growth factor β1 and endothelin-1), and epidermal differentiation (epithelial mesenchymal transition) in the plasma of nemolizumab group.

Conclusions and Relevance

In this cohort study, differences between nemolizumab and placebo groups included modulation of inflammatory signaling, neural development, and epithelial differentiation, suggesting a promising potential approach for clinical management of PN.
Transparency of Results Reporting in Cancer Clinical Trials
Authors: Kao Jennifer , Ross Joseph S. , Miller Jennifer E.
Published: August 2023

This cross-sectional study investigates rates of results reporting among oncology clinical trials across trial registries, medical journals, and medical conferences.
Vitamin D receptor and binding protein genes variants in patients with migraine
Authors: García‐Martín Elena , Navarro‐Muñoz Santiago , Ayuso Pedro , Rodríguez Christopher , Serrador Mercedes , Alonso‐Navarro Hortensia , Calleja Marisol , Espada‐Rubio Silvina , Navacerrada Francisco , Turpín‐Fenoll Laura , Recio‐Bermejo Marta , García‐Ruiz Rafael , Millán‐Pascual Jorge , Plaza‐Nieto José Francisco , García‐Albea Esteban , Agúndez José A.G. , Jiménez‐Jiménez Félix Javier
Published: August 2023

Background/Objectives

Several studies have shown a relationship between vitamin D and migraine, including the association between decreased serum 25‐hydroxyvitamin D in patients with migraine and the positive effects of vitamin D supplementations in the therapy of this disease. Two single‐nucleotide variants (SNVs)vitamin D receptor(VDR) gene,VDRrs2228570, andVDRrs731236 have shown an association with migraine risk in a previous case–control association study, while an exome sequencing study identified a rare variant inGC vitamin D binding proteingene. This study aims to look for the association between several common variants in these two genes and the risk for migraine.

Methods

We genotyped 290 patients diagnosed with migraine and 300 age‐matched controls using specific TaqMan assays forVDRrs2228570,VDRrs731236,VDRrs7975232,VDRrs739837,VDRrs78783628,GCrs7041, andGCrs4588 SNVs.

Results

We did not find an association between these SNVs and the risk for migraine. None of these SNVs were related to the positivity of a family history of migraine or with the presence of aura. TheVDRrs731236A allele showed a significant association with the triggering of migraine attacks by ethanol (Pc = 0.007).

Conclusions

In summary, the results of the current study suggest a lack of association between common SNVs in theVDRandGCgene and the risk of developing migraine. The possible relationship betweenVDRrs731236 and the triggering of migraine episodes with ethanol deserves future studies.
Precipitation of Al3Zr Dispersoids under Various Homogenization and Its Effect on Recrystallization in 2198 Al–Cu–Li Alloy
Authors: Xun ChenYang , Li XiWu , Wen Kai , Geng LiBo , Chen PengCheng , You Wen , Li YaNan , Li ZhiHui , Zhang YongAn , Xiong BaiQing
Published: August 2023

Herein, the precipitation of Al3Zr during one‐ and two‐step homogenization processes is studied by the transmission electron microscopy method, and its effect on recrystallization is investigated by the electron backscattering diffraction technique after the same hot compression and solution treatment, respectively. The results show that when the temperature reaches 430 °C, just some small Al3Zr dispersoids are visible in samples that undergo one‐step treatment. As the first‐step homogenization temperature increases from 365 to 430 °C, Al3Zr radius increases from 9.4 to 19.1 nm while the number density decreases rapidly from 1201 to 183 μm−3. In addition, the average radius of Al3Zr increases to 22.1 nm while the number density decreases to 76 μm−3 when the sample is homogenized at 500 °C/24 h. After a double‐step homogenization with decreased first‐step temperature, lower recrystallization fraction is obtained. Therefore, the optimal homogenization treatment is determined to be 365 °C/16 h + 500 °C/24 h, after which the most desirable Al3Zr distribution and the smallest recrystallization fraction are obtained during thermomechanical process. This result can provide a more appropriate parameter for homogenization treatment in order to achieve a more dispersed distribution, which will result in stronger pinning force during the thermomechanical process.
Multiphysics Simulation and Experimental Investigation of the Densification of Metals by Spark Plasma Sintering
Authors: Semenov A.S. , Trapp J. , Nöthe M. , Kieback B. , Wallmersperger T.
Published: August 2023

Multivariant experimental investigations and multiphysics microstructural modeling of the spark plasma sintering process of metallic powders have been performed up to a relative density of approximately 80%. In comparison, the effect of sintering temperature, pressure, and particle size on the interparticle contact area growth and axial shrinkage of cylindrical specimens of copper and nickel particles is measured in laboratory scaled tests. Herein, for the first time all relevant for sintering phenomena are considered simultaneously: the fully coupled thermo‐electro‐mechanical modeling of the spark plasma sintering processes, additionally taking into account for lattice, grain boundary, surface diffusion, electromigration, and thermomigration, has been carried out. The computational analysis of various physical phenomena allows to identify dominant and insignificant mechanisms. The two‐level numerical simulation includes the modeling of the sintering setup at the macroscopic level and the neck formation process in particle chain systems at the microscopic level. The results of the numerical simulations show a very good agreement with the experimental data. Therefore, the impact of electrical and mechanical loads as well as of particle size on microscopic distribution of temperature, inelastic strain, and on densification has been studied by the finite element simulations.
Effective Treatment of Knee Osteoarthritis Using a Nano‐Enabled Drug Acupuncture Technology in Mice
Authors: Xu Wenjie , Xiao Yu , Zhao Minzhi , Zhu Jiahui , Wang Yu , Wang Wenbin , Wang Peng , Meng Huan
Published: August 2023

A nano‐enabled drug delivery acupuncture technology (nd‐Acu) is developed that is based on traditional acupuncture needles where the stainless‐steel surface is designed to deliver various payload molecules. To create thend‐Acu platform, an electrochemistry procedure is used to attach methyl salicylate‐modified cyclodextrin in which the sugar rings allow the encapsulation of structurally defined single or multiple payload molecules via an inclusion complexation process. Drug loading and release profile are first studied using fluorescent dyes abiotically and at intact animal level.nd‐Acu allows more efficient dye loading and time‐dependent release compared to pristine needles without cyclodextrin modification. Subsequently, a proof‐of‐principle efficacy study is conducted using the platform to load a local anesthetic, lidocaine, for the treatment of knee osteoarthritis (KOA) in mice. It is demonstrated that lidocaine‐ladennd‐Acu can effectively alleviate pain, reduce inflammation, and slow down KOA development biochemically and histologically. Hypothesis‐driven and proteomic approaches are utilized to investigate the working mechanisms of lidocainend‐Acu, indicating that the therapeutic outcome is attributed to the in vivo modulation of the HMGB1/TLR4 signaling pathway. The study also obtained preliminary evidence suggesting the involvement of mitochondria as well as small GTPase such as cdc42 during the treatment by lidocainend‐Acu.
Changes in Tissue Fluidity Predict Tumor Aggressiveness In Vivo
Authors: Sauer Frank , Grosser Steffen , Shahryari Mehrgan , Hayn Alexander , Guo Jing , Braun Jürgen , Briest Susanne , Wolf Benjamin , Aktas Bahriye , Horn Lars‐Christian , Sack Ingolf , Käs Josef A.
Published: August 2023

Cancer progression is caused by genetic changes and associated with various alterations in cell properties, which also affect a tumor's mechanical state. While an increasedstiffnesshas been well known for long for solid tumors, it has limited prognostic power. It is hypothesized that cancer progression is accompanied by tissuefluidization, where portions of the tissue can change position across different length scales. Supported by tabletop magnetic resonance elastography (MRE) on stroma mimicking collagen gels and microscopic analysis of live cells inside patient derived tumor explants, an overview is provided of how cancer associated mechanisms, including cellular unjamming, proliferation, microenvironment composition, and remodeling can alter a tissue'sfluidityandstiffness. In vivo, state‐of‐the‐art multifrequency MRE can distinguish tumors from their surrounding host tissue by their rheological fingerprints. Most importantly, a meta‐analysis on the currently available clinical studies is conducted and universal trends are identified. The results and conclusions are condensed into a gedankenexperiment about how a tumor can grow and eventually metastasize into its environment from a physics perspective to deduce corresponding mechanical properties. Based onstiffness, fluidity,spatial heterogeneity, andtextureof thetumor fronta roadmap for a prognosis of a tumor's aggressiveness and metastatic potential is presented.
Enhanced UV Light‐Emission of Zinc‐Phosphate‐Hydrate Hydrothermally‐Grown on Cu Metal Substrates for Opto‐Electronic Applications
Authors: Spiegelhoff Yuting , Zemajtis Filip , Kheirandish Elaheh , Grauby Olivier , Ferry Daniel , Pellenq Roland J.‐M. , Sobolev Konstantin , Kouklin Nikolai
Published: August 2023

In the present study, polycrystalline films of layered zinc phosphate hydrate are produced by a facile, low‐temperature single‐step hydrothermal fabrication method on top of Cu metal substrates. Despite containing structural water, the as‐grown films remain crystalline, chemically stable, and electrically conductive. The photoluminescence spectrum obtained at room‐temperature reveals the presence of a spectrally narrow, high‐intensity ultraviolet band that consists of two Gaussian peaks at ≈377 and 383 nm and a UV‐to‐visible peak emission intensity ratio of ≈5.3. The electrical charge‐transport properties remain Ohmic for electric fields of up to ≈2 kV m−1 and temperature (T) range of ≈223–368 K. The electrical conductivity is further found to vary exponentially with the inverse temperature, and the thermal activation energy, Ea is 285 ± 8 meV. A moderate UV‐vis photoconduction effect is registered and assigned to light‐assisted electronic transitions that involve near‐band edge defect states. This study can potentially open a door to the engineering and deployment of water‐based compounds with advanced, semiconducting‐like attributes in short‐wavelength opto‐electronic devices.
Bipolar Membrane with Porous Anion Exchange Layer for Efficient and Long‐Term Stable Electrochemical Reduction of CO2 to CO
Authors: Disch Joey , Ingenhoven Stefan , Vierrath Severin
Published: August 2023

Bipolar membranes in forward bias have the potential to address several challenges of alkaline zero‐gap CO2 electrolyzers. However, the inevitable gas evolution of CO2 at the membrane junction typically leads to delamination and failure of the membrane after a few hours, limiting its applicability in electrolyzers so far. In this work, a bipolar membrane with a perforated anion exchange layer is presented that allows the CO2 gas to flow back to the cathode and thus preventing accumulation of gas at the junction. This configuration for the first time enables stable operation of a forward bias bipolar membrane showing a degradation rate of 0.5 mV h−1 in a 200 h constant current hold at 100 mA cm−2 and 3.1 V. Highest reported energy efficiency of EECO = 39% and Faradaic efficiency of FECO = 96% at 200 mA cm−2 among forward bipolar membranes prove that the perforated membrane does not compromise efficiency. A maximum CO2 single‐pass conversion of 52% at 0.75 mLCO2 min−1 cm−2 and a low specific energy consumption of 665 kJ mol−1 CO2 shows that this concept is superior not only to other bipolar membranes in the literature, but potentially also to conventional anion exchange membrane‐based electrolyzers.
The impact of tau deposition and hypometabolism on cognitive impairment and longitudinal cognitive decline
Authors: Boccalini Cecilia , Ribaldi Federica , Hristovska Ines , Arnone Annachiara , Peretti Débora Elisa , Mu Linjing , Scheffler Max , Perani Daniela , Frisoni Giovanni B. , Garibotto Valentina
Published: August 2023

INTRODUCTION

Tau and neurodegeneration strongly correlate with cognitive impairment, as compared to amyloid. However, their contribution in explaining cognition and predicting cognitive decline in memory clinics remains unclarified.

METHODS

We included 94 participants with Mini‐Mental State Examination (MMSE), tau positron emission tomography (PET), amyloid PET, fluorodeoxyglucose (FDG) PET, and MRI scans from Geneva Memory Center. Linear regression and mediation analyses tested the independent and combined association between biomarkers, cognitive performance, and decline. Linear mixed‐effects and Cox proportional hazards models assessed biomarkers’ prognostic values.

RESULTS

Metabolism had the strongest association with cognition (r = 0.712; p < 0.001), followed by tau (r = ‐0.682; p < 0.001). Neocortical tau showed the strongest association with cognitive decline (r = ‐0.677; p < 0.001). Metabolism mediated the association between tau and cognition and marginally mediated the one with decline. Tau positivity represented the strongest risk factor for decline (hazard ratio = 32).

DISCUSSION

Tau and neurodegeneration synergistically contribute to global cognitive impairment while tau drives decline. The tau PET superior prognostic value supports its implementation in memory clinics.

Highlights

Hypometabolism has the strongest association with concurrent cognitive impairment.

Neocortical tau pathology is the main determinant of cognitive decline over time.

FDG‐PET has a superior value compared to MRI as a measure of neurodegeneration.

The prognostic value of tau‐PET exceeded all other neuroimaging modalities.
Supporting collaborative dissection through the development of an online wiki positively impacts the learning of veterinary anatomy
Authors: Previdelli Renato L. , Boardman Emma , Frill Michael , Frean Stephen , Channon Sarah B.
Published: August 2023

An innovative series of dissections of the canine abdomen was created to facilitate social distancing in the dissection room following COVID‐19 restrictions imposed in the UK. In groups of six, first‐year veterinary students took turns dissecting selected parts of the canine abdomen while maintaining social distancing and documenting their work with video and photographs. Here, students learned about the canine abdominal anatomy by dissecting, recording the dissections of others in their group, and compiling the recorded material into a collaborative electronic media portfolio (Wiki). An online formative multiple‐choice test was created to test students' knowledge of the canine abdominal anatomy. The result analysis showed that although students achieved the learning outcomes only by studying the Wiki, they had better performance in the anatomical areas where they learned through the dissection (p < 0.05). Student performance was very similar in the areas in which they were present in the dissection room and participated in recording the dissection compared with the areas that they effectively dissected (p > 0.05). A qualitative thematic analysis was developed to understand students' opinions via their feedback on this dissection approach. Our results showed that student collaboration and the development of practical skills were the most valued aspects of this dissection teaching initiative. Moreover, these results show that developing a group Wiki has a positive impact on student achievement of learning objectives, with a practical hands‐on dissection being fundamental for the optimal learning of the canine abdominal anatomy.
High performance anion exchange chromatography purification of probiotic bacterial extracellular vesicles enhances purity and anti‐inflammatory efficacy
Authors: Pirolli Nicholas H. , Reus Laura Samantha C. , Mamczarz Zuzanna , Khan Sulayman , Bentley William E. , Jay Steven M.
Published: August 2023

Bacterial extracellular vesicles (BEVs), including outer membrane vesicles, have emerged as a promising new class of vaccines and therapeutics to treat cancer and inflammatory diseases, among other applications. However, clinical translation of BEVs is hindered by a current lack of scalable and efficient purification methods. Here, we address downstream BEV biomanufacturing limitations by developing a method for orthogonal size‐ and charge‐based BEV enrichment using tangential flow filtration (TFF) in tandem with high performance anion exchange chromatography (HPAEC). The data show that size‐based separation coisolated protein contaminants, whereas size‐based TFF with charged‐based HPAEC dramatically improved purity of BEVs produced by probiotic Gram‐negative Escherichia coli and Gram‐positive lactic acid bacteria (LAB). Escherichia coli BEV purity was quantified using established biochemical markers while improved LAB BEV purity was assessed via observed potentiation of anti‐inflammatory bioactivity. Overall, this work establishes orthogonal TFF + HPAEC as a scalable and efficient method for BEV purification that holds promise for future large‐scale biomanufacturing of therapeutic BEV products.