bluuebunny/crossref_metadata_2025 huggingface dataset:
FORECASTING METHOD SINGLE EXPONENTIAL SMOOTHING FOR DEMAND GROCERIES AT THE GUNTUR STORE
Authors: Irsyah Ahmad Aziz , Risnawati Risnawati , Efendi Zulfan
Published: April 2024

Abstract: Guntur Store is located on Jl. Sisingamangaraja, Kisaran, Asahan Regency. It focuses on selling basic needs, but the store faces a problem in its sales. The main issue encountered is the uncertainty in forecasting the stock of basic needs, which can lead to imbalance between supply and demand, due to Guntur Store still relying on manual ledger entries for reporting and inputting data into Microsoft Excel. This research aims to predict the demand for basic needs at Guntur Store using the Single Exponential Smoothing Method and to enhance prediction accuracy through the application of time series analysis techniques on historical sales data. The Single Exponential Smoothing Method will be employed to model and forecast patterns of demand for staple goods. The findings of this research can provide insights into future demand for goods, thereby improving supply chain optimization and ensuring adequate stock levels to effectively meet customer demands. The conclusion of this study is to obtain more accurate estimates in anticipating the evolving data patterns of basic needs at Guntur Store, thus providing valuable information for the store and policymakers involved in the distribution of basic needs.Keywords: basic food needs; forecasting; single exponential smoothing                  Abstrak : Toko Guntur terletak di Jl. Sisingamangaraja, Kisaran, Kabupaten Asahan. Berfokus pada penjualan kebutuhan sembako, namun dalam penjualan toko tersebut mengalami sebuah permasalahan. Permasalahan utama yang dihadapi adalah ketidakpastian dalam meramalkan kebutuhan stok Sembako yang dapat mengakibatkan ketidakseimbangan antara pasokan dan permintaan, dikarenkan Toko Guntur masih menggunakan buku besar dalam pembuatan laporan dan di input ke dalam microsoft excel. Penelitian ini bertujuan untuk memprediksi permintaan Sembako di Toko Guntur menggunakan Metode Single Exponential Smoothing serta meningkatkan akurasi prediksi melalui penerapan teknik analisis deret waktu terhadap data penjualan historis. Metode Single Exponential Smoothing akan digunakan untuk memodelkan dan memprediksi pola permintaan barang pokok. Hasil penelitian ini dapat memberikan jumlah permintaan barang di masa mendatang sehingga optimalisasi rantai pasok menjadi g lebih baik dan memastikan tingkat stok yang memadai untuk memenuhi permintaan pelanggan secara efektif. Kesimpulan penelitian ini untuk mendapatkan perkiraan yang lebih akurat dalam mengantisipasi pola data yang sedang berkembang kebutuhan sembako pada Toko Guntur sehingga menghasilkan informasi yang akurat dapat menjadi sumber informasi berharga bagi Toko Guntur, dan pembuat kebijakan yang terlibat dalam distribusi Sembako.Kata Kunci:  kebutuhan sembako; single exponential smoothing; peramalan
Hugh Sykes Davies's Petron: Surrealism, Politics, and Hiking
Authors: Byers Mark
Published: April 2024

Published a year before the landmark London International Surrealist Exhibition of 1936, Hugh Sykes Davies's prose poem Petron continues to resist both aesthetic and political categorisation. This essay clarifies Petron's contribution to the Surrealist movement in England by reading its densely allusive text as one which limns Surrealist technique and Marxist theory within a specifically English rural setting. Identifying the wanderings of its hero, Petron, as a Surrealist riff on the popular communist hikes or ‘Red Rambles’ of the 1930s, the essay shows how Petron combines radical politics and Surrealist method in its phantasmagoric representation of a fenced, enclosed, degraded, and often inaccessible English landscape.
‘Fact’ and ‘Truth’: Empire and Culture in David Jones’ The Grail Mass
Authors: Enwright Catherine
Published: April 2024

David Jones’ recently published long poem, The Grail Mass, poignantly re-imagines the events leading to Christ's crucifixion through the eyes of two Roman legionaries who are detailed to stand guard at the cross. Jones uses the poem's Biblical re-telling to juxtapose two visions of society: the world of ‘truth’, by which he means cultures that spring from tradition and religious belief and the world of ‘fact’, by which he means rationalist societies organized around the utilitarian pursuit of land, wealth and resources. I first explore Jones’ poetic understanding of ‘truth’ and ‘fact’ in The Grail Mass, and then consider his identification of similar forces in modernity, through an examination of an unpublished 1939 essay in which Jones’ wrestles with the ways in which pre-war totalitarian rulers, especially Hitler, co-opted his ideal of a traditional culture, or world of ‘truth’, to facilitate dictatorial and imperialist aims.
Modern professional equipment and technologies at Intergeo 2023 in Berlin
Authors:   Lviv Polytechnic National University, Thevoho I. , CHETVERIKOV B. ,   Lviv Polytechnic National University, TRYUKHAN M. ,   Research Institute of Geodesy and Cartography
Published: April 2024

Detailed information is provided about the demonstration of new geodetic and photogrammetric equipment, mobile systems and robotic complexes, cutting-edge technologies, and trends in modern professional research presented at the powerful world exhibition (Messegedende) and extensive and multi-themed conference at the next World Geodetic Congress INTERGEO 2023 in Berlin (Germany), including the participation of enterprises, firms, public organizations, scientists, experts from Ukraine, and the delegation of UTGK. The content and results of the Society’s delegation work at the congress, particularly in its exhibition pavilion, are highlighted.
25 years of Yavoriv SGP – structure, usage, research scope, prospects
Authors:   Lviv Polytechnic National University, Thevoho I. , TSIUPAK I. ,   Lviv Polytechnic National University, VANCHURA O. ,   Lviv Polytechnic National University, CHETVERIKOV B. ,   Volyn National University named after Lesi Ukrainka
Published: April 2024

This paper presents detailed information about the stages of creation and directions of use of a special multifunctional standard scientific geodetic polygon (SGP) in Yavoriv district of Lviv region. The main purpose of the SGP is the metrological control of modern geodetic instruments and the testing of new technologies. The features of constructing geodetic networks, creating a local reference gravimetric network to refine the parameters of the global Earth gravimetric model, and constructing a quasi-geoid model with centimeter accuracy within the local polygon are described. The determination of high-precision astronomical coordinates and reference azimuths with an accuracy of 0.5–1.0, the creation of metrological objects of the NGP are outlined: the standard linear baseline (SLB) of original design and the fundamental geodetic network (FGN) for conducting special research and metrological verification of electronic theodolites, rangefinders, GNSS receivers, the development of a high-precision leveling network for studying accuracy and GNSS-leveling, etc. It provides information about multi-year experimental calibrations of the SLB using various methods and devices, and the first international intercomparisons on the SLB (working standard) in Ukraine, as well as multi-day GNSS observation campaigns at FGN points, the results of processing, and the achieved high accuracy. New experimental studies are related to improving the accuracy of FGN and GNSS leveling, new calibrations of SLB, including international intercomparisons, establishment of fundamental gravimetric points, optimization of the use of reference directions for metrological control and calibration of navigation equipment.
Automatic completion of geometric models from point clouds for analyzing historic timber roof structures
Authors: Özkan Taşkın , Pfeifer Norbert , Hochreiner Georg
Published: April 2024

Laser scanners are being increasingly utilized in the engineering community to collect accurate and dense 3D data on timber roof structures. Point clouds, which are produced by either scanning or photogrammetry, can be subsequently processed using specialized software to create geometric models of individual components of the roof structure manually. Manual modeling of each structural element in a computer-aided-design-based structural analysis software application is a labor-intensive and time-consuming process, whereas automatic modeling typically yields incomplete results in terms of the numbers and sizes of individual beams owing to shortcomings in data acquisition or data processing. In the context of structural assessment, full-scale modeling of each beam is mandatory for a holistic analysis of structural health. This study addresses the gap between automated roof-structure models and preliminary structural assessments through a hierarchical analysis and refinement of the geometric model. The proposed method was applied to two different roof structures, and structural assessments show that it is feasible to import and process the generated models in a structural analysis software application. The resulting structural models indicate that the workflow improves the months of time consumed by optional mistakes from manual contributions to less than a week without the uncertainties caused by human error.
Overexpression of Fgf18 in cranial neural crest cells recapitulates Pierre Robin sequence in mice
Authors: Lv Yi , Wang Qian , Lin Chensheng , Zheng Xi , Zhang Yanding , Hu Xuefeng
Published: April 2024

The pivotal role of FGF18 in the regulation of craniofacial and skeletal development has been well established. Previous studies have demonstrated that mice with deficiency in Fgf18 exhibit severe craniofacial dysplasia. Recent clinical reports have revealed that the duplication of chromosome 5q32-35.3, which encompasses the Fgf18 gene, can lead to cranial bone dysplasia and congenital craniosynostosis, implicating the consequence of possible overdosed FGF18 signaling. This study aimed to test the effects of augmented FGF18 signaling by specifically overexpressing the Fgf18 gene in cranial neural crest cells using the Wnt1-Cre;pMes-Fgf18 mouse model. The results showed that overexpression of Fgf18 leads to craniofacial abnormalities in mice similar to the Pierre Robin sequence in humans, including abnormal tongue morphology, micrognathia, and cleft palate. Further examination revealed that elevated levels of Fgf18 activated the Akt and Erk signaling pathways, leading to an increase in the proliferation level of tongue tendon cells and alterations in the contraction pattern of the genioglossus muscle. Additionally, we observed that excessive FGF18 signaling contributed to the reduction in the length of Meckel’s cartilage and disrupted the development of condylar cartilage, ultimately resulting in mandibular defects. These anomalies involve changes in several downstream signals, including Runx2, p21, Akt, Erk, p38, Wnt, and Ihh. This study highlights the crucial role of maintaining the balance of endogenous FGF18 signaling for proper craniofacial development and offers insights into potential formation mechanisms of the Pierre Robin sequence.
Longitudinal change of serum exosomal miR-186-5p estimates major adverse cardiac events in acute myocardial infarction patients receiving percutaneous coronary intervention
Authors: Ren Lingyun , Liu Wei , Chen Shanshan , Zeng Haibo
Published: April 2024

Objective

Our recently published study discovers that exosomal microRNA (miR)-186-5p promotes vascular smooth muscle cell viability and invasion to facilitate atherosclerosis. This research aimed to explore the prognostic implication of serum exosomal miR-186-5p in acute myocardial infarction (AMI) patients receiving percutaneous coronary intervention (PCI).

Methods

One hundred and fifty AMI patients receiving PCI and 50 healthy controls (HCs) were screened. Serum exosomal miR-186-5p was detected by reverse transcriptase-quantitative polymerase chain reaction assay in AMI patients at admission and after PCI, as well as in HCs after enrollment. Major adverse cardiac events (MACE) were recorded during follow-up in AMI patients receiving PCI.

Results

Serum exosomal miR-186-5p was raised in AMI patients vs. HCs (P < 0.001). Besides, serum exosomal miR-186-5p was positively linked to body mass index (P = 0.048), serum creatinine (P = 0.021), total cholesterol (P = 0.029), and C-reactive protein (P = 0.018); while it was reversely linked with estimated glomerular filtration rate (P = 0.023) in AMI patients. Interestingly, serum exosomal miR-186-5p was correlated with the diagnosis of ST-segment elevation myocardial infarction (P = 0.034). Notably, serum exosomal miR-186-5p was decreased after PCI vs. at admission (P < 0.001). The 6-, 12-, 18-, and 24-month accumulating MACE rates were 4.5%, 8.9%, 14.8%, and 14.8% in AMI patients. Furthermore, serum exosomal miR-186-5p ≥3.39 (maximum value in HCs) after PCI (P = 0.021) and its decrement percentage <median (35%) decrement (P = 0.044) estimated elevated MACE in AMI patients.

Conclusion

Serum exosomal miR-186-5p is reduced after PCI, and its post-PCI high level or minor decrease estimates increased MACE risk in AMI patients.
A mini-review on trading mechanisms of emerging joint energy markets with high shares of renewables
Authors: Gao Xiang , Yang Chongming , Zhu Ziqing , Wu Yuheng , Chen Yapeng , Mu Zhiying
Published: April 2024

The intermittence and unpredictability of large-scale renewable integration poses significant challenges to the operation of the electricity market. New paradigms of the joint electricity spot market (EM) and ancillary service market (ASM) incorporating frequency regulation (FR) and flexible ramping product (FRP) are considered as potential solutions, addressing the challenge of limited compatibility in the electricity market with the widespread integration of renewable sources. This work focuses on three critical technical obstacles: optimizing the joint market mechanisms, constructing bidding models, and exploring algorithmic solutions. This paper presents a brief review of recent research on bidding mechanisms, models, and strategies for the electricity joint market with high-penetration renewable integration. Furthermore, challenges and future research prospects of these issues are also discussed.
Research trends in the use of secondary batteries for energy storage
Authors: García-Pineda Vanessa , Valencia-Arias Alejandro , Zapata Ochoa Edison Andrés , Sánchez-Santos Gustavo , Gastiaburú-Morales Silvia Yvone , Palacios-Moya Lucia
Published: April 2024

Introduction: This study addresses the use of secondary batteries for energy storage, which is essential for a sustainable energy matrix. However, despite its importance, there are still important gaps in the scientific literature. Therefore, the objective is to examine the research trends on the use of secondary batteries for energy storage and to assess their development and direction.

Methods: A bibliometric analysis is used, following the PRISMA-2020 guidelines for the analysis of secondary sources. 98 studies were identified and analyzed in the bibliometric evaluation category. Although this is a review of different research documents and different types of batteries are addressed, the study focuses mainly on the identification of the different existing trends in the use of second-use batteries for energy storage.

Results: The study’s findings show a significant increase in interest, particularly in 2023, 2022, and 2021. Key researchers such as Zakeri and Kulcinski, as well as journals like Energy Conversion and Management, have made significant contributions. The significance of the topic is highlighted by the annual production of articles. The leading research in this field comes from the United States and China, with a shift in focus towards specific areas such as thermal assessment and storage. Thematic clusters include life cycle analysis, thermal storage, and lithium-ion batteries. Emerging terms such as ‘smart grid’ and ‘exergy’ indicate a growing interest.

Discussion: Understanding trends in battery research is crucial for developing sustainable energy solutions and addressing global energy challenges.
Non-target screening to track contaminant removal and release during nature-based water treatment
Authors: Guy Charlotte , Duporté Geoffroy , Luquot Linda , Gomez Elena
Published: April 2024

Introduction: Population growth and increasing water demand have exacerbated water resource scarcity. Treated wastewater (TWW) is a valuable alternative resource, but its complex composition, including micropollutants, raises concerns about reuse risks. Reactive barriers (RB) made with natural materials offer a solution to remove TWW contaminants. Evaluating RB process effectiveness and comprehending contaminant fate remain challenging. Recent advances in High-Resolution Mass Spectrometry (HRMS) and non-target analysis (NTA) provide an opportunity to identify contaminants and evaluate RB processes. The study aims to develop an NTA approach to assess RB effectiveness and understand the NTA contribution for broadening perspectives on the impact of reactive barrier treatment.

Methods: In a serie of batch experiments, TWW was mixed with a RB under two conditions: TWW in contact with RB (TWW+RB) and TWW alone (TWW). After 1 h of contact, samples were extracted and analyzed using HPLC-HRMS. NTA workflow and statistical comparison between the two sample conditions were applied for data treatment. Additionally, a quantitative method was applied to 28 pharmaceutical residues. Sorption (%) was calculated by comparing concentrations in TWW+RB and TWW experiments. NTA’s applicability for sorption estimation was investigated using intensities from differential analysis.

Results: Differential analysis shows significant differences in compounds that decrease or increase after contact with BR. A prioritization workflow identified and annotated 115 compounds. Natural products predominantly increased after RB contact, while compounds exhibited a significant 75% decrease in peak area are mainly pharmaceuticals. Notably, 61% of these molecules were sorbed at more than 50%. The sorption of emerging contaminants (ECs) estimated by NTA correlated satisfactorily with sorption quantified through target analysis, although caution regarding the matrix effect is necessary.

Discussion: NTA provides a comprehensive view of RB treatment performance, giving information on the compounds released by the barrier and its sorption capacity. NTA emphasizes the benefits of RB treatment while highlighting the need to study compounds reloaded by RB. It is a powerful tool for understanding the advantages of nature-based reactive barrier treatment in improving the quality of TWW.
Anti-SARS-CoV-2 glyco-humanized polyclonal antibody XAV-19: phase II/III randomized placebo-controlled trial shows acceleration to recovery for mild to moderate patients with COVID-19
Authors: Poulakou Garyfallia , Royer Pierre-Joseph , Evgeniev Nikolay , Evanno Gwénaëlle , Shneiker Françoise , Marcelin Anne-Geneviève , Vanhove Bernard , Duvaux Odile , Marot Stéphane , Calvez Vincent
Published: April 2024

Introduction

XAV-19 is a glyco-humanized swine polyclonal antibody targeting SARS-CoV-2 with high neutralizing activity. The safety and clinical efficacy of XAV-19 were investigated in patients with mild to moderate COVID-19.

Methods

This phase II/III, multicentric, randomized, double-blind, placebo-controlled clinical trial was conducted to evaluate the safety and clinical efficacy of XAV-19 in patients with a seven-point WHO score of 2 to 4 at randomization, i.e., inpatients with COVID-19 requiring or not requiring low-flow oxygen therapy, and outpatients not requiring oxygen (EUROXAV trial, NCT04928430). Adult patients presenting in specialized or emergency units with confirmed COVID-19 and giving their consent to participate in the study were randomized to receive 150 mg of XAV-19 or placebo. The primary endpoint was the proportion of patients with aggravation within 8 days after treatment, defined as a worsening of the seven-point WHO score of at least one point between day 8 and day 1 (inclusion). The neutralization activity of XAV-19 against variants circulating during the trial was tested in parallel.

Results

From March 2021 to October 2022, 279 patients received either XAV-19 (N = 140) or placebo (N = 139). A slow enrollment and a low rate of events forced the termination of the premature trial. XAV-19 was well tolerated. Underpowered statistics did not allow the detection of any difference in the primary endpoint between the two groups or in stratified groups. Interestingly, analysis of the time to improvement (secondary endpoint) showed that XAV-19 significantly accelerated the recovery for patients with a WHO score of 2 or 3 (median at 7 days vs. 14 days, p = 0.0159), and even more for patients with a WHO score of 2 (4 days vs. 14 days, p = 0.0003). The neutralizing activity against Omicron and BA.2, BA.2.12.1, BA.4/5, and BQ.1.1 subvariants was shown.

Discussion

In this randomized placebo- controlled trial with premature termination, reduction of aggravation by XAV-19 at day 8 in patients with COVID-19 was not detectable. However, a significant reduction of the time to improvement for patients not requiring oxygen was observed. XAV-19 maintained a neutralizing activity against SARS-CoV-2 variants. Altogether, these data support a possible therapeutic interest for patients with mild to moderate COVID-19 requiring anti-SARS-CoV-2 neutralizing antibodies.

Clinical Trial Registration:

https://clinicaltrials.gov/, identifier NCT04928430; https://www.clinicaltrialsregister.eu/about.html (EudraCT), identifier 2020-005979-12.
High interleukin-6 levels induced by COVID-19 pneumonia correlate with increased circulating follicular helper T cell frequency and strong neutralization antibody response in the acute phase of Omicron breakthrough infection
Authors: Kawasuji Hitoshi , Morinaga Yoshitomo , Nagaoka Kentaro , Tani Hideki , Yoshida Yoshihiro , Yamada Hiroshi , Takegoshi Yusuke , Kaneda Makito , Murai Yushi , Kimoto Kou , Niimi Hideki , Yamamoto Yoshihiro
Published: April 2024

Background

Acute immune responses to coronavirus disease 2019 (COVID-19) are influenced by variants, vaccination, and clinical severity. Thus, the outcome of these responses may differ between vaccinated and unvaccinated patients and those with and without COVID-19-related pneumonia. In this study, these differences during infection with the Omicron variant were investigated.

Methods

A total of 67 patients (including 47 vaccinated and 20 unvaccinated patients) who were hospitalized within 5 days after COVID-19 symptom onset were enrolled in this prospective observational study. Serum neutralizing activity was evaluated using a pseudotyped virus assay and serum cytokines and chemokines were measured. Circulating follicular helper T cell (cTfh) frequencies were evaluated using flow cytometry.

Results

Twenty-five patients developed COVID-19 pneumonia on hospitalization. Although the neutralizing activities against wild-type and Delta variants were higher in the vaccinated group, those against the Omicron variant as well as the frequency of developing pneumonia were comparable between the vaccinated and unvaccinated groups. IL-6 and CXCL10 levels were higher in patients with pneumonia than in those without it, regardless of their vaccination status. Neutralizing activity against the Omicron variant were higher in vaccinated patients with pneumonia than in those without it. Moreover, a distinctive correlation between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions was observed only in vaccinated patients.

Conclusions

The present study demonstrates the existence of a characteristic relationship between neutralizing activity against Omicron, IL-6 levels, and cTfh proportions in Omicron breakthrough infection.
Impacts of large scale climate modes on the current and future bimodal wave climate of a semi-protected shallow gulf
Authors: Perry Benjamin , Huisman Bas , Antolínez José A. A. , Hesp Patrick A. , Miot da Silva Graziela
Published: April 2024

The bimodal wave climate of the semi-protected shallow Gulf St Vincent in South Australia has been analyzed through a forty-year (1980-2020) wave hindcast and an investigation into the climatic drivers of wave climate anomalies is presented. The sea and swell partitions of the wave climate were modelled independently as well as using an integrated model with both partitions represented. The wave hindcast was validated against two wave buoys located off the coast of Adelaide’s metropolitan beaches and key wave parameter anomalies were calculated across the gulf. Teleconnections were investigated, and the Southern Annular Mode is found to have the strongest correlations to wave parameter anomalies while the Southern Oscillation Index and the Dipole Mode Index fluctuations are found to correlate seasonally with wave parameter anomalies. Projected future trends of these climate drivers from literature have been related to the teleconnections found in this study to inform future trends of bimodal wave conditions in the gulf. The Southern Annular Mode is projected to trend positive which will reduce wave height and the westerly component of waves in the gulf, while the Southern Oscillation Index is projected to become more variable in the future which will lead to more extreme winter and spring wave conditions. An understanding of these trends allows coastal managers to pre-emptively manage the impacts of waves on the coastline at a seasonal to annual basis and provides insight into future wave conditions beyond these time periods.
Effect of Mn-content of ER5356 welding rods on mechanical properties of Al-alloys joints
Authors: Ni Xianpeng , Xu Shaohua , Mu Hua
Published: April 2024

Introduction: Compared with imported welding wire, domestic aluminum alloy welding wire has more internal inclusion defects. To improve the welding quality and reliability of aluminum alloy, the welding performance of aluminum alloy was improved by adding different content of Mn element.

Methods: ER5356 aluminum alloy ingot with different Mn content (0.05% and 0.15%) was prepared by semi-continuous casting and gravity casting. After stretching, the mechanical properties and microstructure of ER5356 aluminum alloy were studied. In addition, the microstructure, microhardness and mechanical behavior of ER5356 aluminum alloy welding wire with 6082 and 7005 aluminum alloy joints were studied.

Results and Discussion: Compared with gravity casting, the yield strength and tensile strength of ER5356 (0.15% Mn) were increased by 12.8% and 3.17% respectively. The head influence zone of the joint made of metal wire containing 0.15% Mn is slightly wider than that of the joint made of ER535 (0.05% Mn) containing 0.05% Mn. The quality of ER5356 aluminum alloy welding wire blocked by semi-continuous casting is better than that of ER5356 aluminum alloy welding wire blocked by gravity casting method. Mn element can improve the metal deposition process in welding.

Conclusion: The research method can improve the welding current control and welding quality, and has important practical significance in improving the mechanical properties of welding seams.
Competing risk nomogram predicting cause-specific mortality in older patients with testicular germ cell tumors
Authors: Wu Xiaoying , Zhou Mingfei , Lyu Jun , Chen Lin
Published: April 2024

Background

Testicular germ cell tumor (TGCT) is the most common type of malignancy in young men, but rarely in older adults. We aimed to construct a competing risk model to predict the prognosis for older patients with TGCT.

Methods

We collected TGCT patients aged 50 years or older diagnosed between 2004 and 2015 from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database. We estimated the cumulative incidences of cause-specific death (CSD) and other causes of death and established a nomogram predicting cause-specific mortality in older patients with TGCT by Fine-Gray competing risk regression. The concordance index (C-index), calibration curves, area under the receiver operating characteristic curve (AUC), and decision analysis curves (DCA) were used to evaluate the differentiation, accuracy, and clinical significance of the nomogram.

Results

A total of 2,751 older TGCT patients were included in the study. The 3-, 5-, and 10-year cumulative incidences were 4.4, 5.0 and 6.1%, respectively, for cause-specific death, and 3.8, 6.2, 13.1%, respectively, for other causes of death. Predictors of cause-specific mortality in older TGCT included age, marital status, annual household income, histology, tumor size, stage and surgery. In the training and validation sets, the C-indexes were greater than 0.8, indicating that the nomogram had good discrimination. The AUC revealed the same result. The calibration curves showed good agreement between the predicted and observed results of the nomogram. DCA curves indicated that the nomogram had more clinical significance than the conventional American Joint Committee on Cancer (AJCC) staging. Based on the total nomogram score of each case, all patients were categorized into low-risk and high-risk groups, and risk categorization allowed the identification of cases with a high risk of death.

Conclusion

We established a competing risk nomogram with good performance that may help clinicians accurately predict the prognosis of older TGCT patients.
Treatment of atopic dermatitis with upadacitinib: adcare single center experience
Authors: Fomina Daria S. , Mukhina Olga A. , Mikhailova Valeria I. , Lebedkina Marina S. , Sedova Elizaveta L. , Bobrikova Elena N. , Elisyutina Olga G. , Fedenko Elena S. , Nurpeisov Tair T. , Karaulov Alexander V. , Lysenko Mar’yana A. , Ensina Luis Felipe C.
Published: April 2024

Introduction

The role of upadacitinib in the management of moderate to severe atopic dermatitis seems promising, but more data on its efficacy and safety are needed. This study endeavors to assess the practical impact and safety of upadacitinib in patients with moderate to severe atopic dermatitis. The study aims to evaluate the efficacy and safety of upadacitinib in the treatment of moderate to severe atopic dermatitis, focusing on analyzing patient responses to the treatment.

Methods

In this study, adult patients diagnosed with moderate to severe atopic dermatitis received upadacitinib at daily doses of 15 mg or 30 mg, as prescribed by their attending physicians. The therapeutic efficacy of upadacitinib was meticulously assessed using established clinical metrics. Simultaneously, a comprehensive safety assessment was conducted through monthly monitoring, including the evaluation of potential effects of upadacitinib intake on hepatic function, lipid profile, and hematopoiesis using the pertinent laboratory tests.

Results

Sixteen participants were enrolled in the study. At 1month follow-up, there was a significant reduction in the mean Eczema Area and Severity Index (EASI) score to 18.8 points, which further increased to 24 points at the 4-month mark. Additionally, 9 participants (56%) demonstrated an EASI-50 response after 1 month of treatment, with this response increasing to 9 participants (90%) after 4 months. Furthermore, enhanced therapeutic responses were observed at 4 months, with 6 patients (38%) achieving an EASI-75 response at 1month and 8 patients (80%) achieving this milestone at the 4-month follow-up. This study highlights the potential of upadacitinib as an effective treatment option for moderate to severe atopic dermatitis. While it demonstrates improved symptom management, close monitoring for potential adverse events, particularly infections and the known risks of Janus kinase inhibitors, is essential. Further research is essential to determine the long-term safety and efficacy of upadacitinib.
Comparison of the fecal microbiota of adult healthy dogs fed a plant-based (vegan) or an animal-based diet
Authors: Liversidge Brooklynn D. , Gomez Diego E. , Dodd Sarah A. S. , MacNicol Jennifer L. , Adolphe Jennifer L. , Blois Shauna L. , Verbrugghe Adronie
Published: April 2024

Purpose

Pet guardians are increasingly seeking vegan dog foods. However, research on the impact of these diets on gastrointestinal (GI) physiology and health is limited. In humans, vegan diets modify the GI microbiota, increasing beneficial digestive microorganisms. This study aimed to examine the canine fecal microbiota in response to a vegan diet compared to an animal-based diet.

Methods

Sixty-one client-owned healthy adult dogs completed a randomized, double-blinded longitudinal study. Dogs were randomly assigned into two groups that were fed either a commercial extruded animal-based diet (MEAT, n = 30) or an experimental extruded vegan diet (PLANT, n = 31) for 12 weeks. Fecal collections occurred at the start of the experimental period and after 3 months of exclusively feeding either diet. Bacterial DNA was extracted from the feces, and the V4 region of the 16S rRNA gene was amplified using PCR and sequenced on Illumina MiSeq. Beta-diversity was measured using Jaccard and Bray–Curtis distances, and the PERMANOVA was used to assess for differences in fecal microbiota within and between groups. Alpha-diversity indices for richness, evenness, and diversity, as well as relative abundance, were calculated and compared between groups.

Results

Beta-diversity differences occurred between diet groups at exit time-point with differences on Bray–Curtis distances at the family and genus levels (p = 0.007 and p = 0.001, respectively), and for the Jaccard distance at the family and genus level (p = 0.006 and p = 0.011, respectively). Significant differences in alpha-diversity occurred when comparing the PLANT to the MEAT group at the exit time-point with the PLANT group having a lower evenness (p = 0.012), but no significant differences in richness (p = 0.188), or diversity (p = 0.06). At exit-timepoint, compared to the MEAT group, the relative abundance of Fusobacterium, Bacteroides, and Campylobacter was lower in the PLANT group. The relative abundance of Fusobacterium decreased over time in the PLANT group, while no change was observed in the MEAT group.

Conclusion

These results indicate that vegan diets may change the canine gut microbiota. Future studies are warranted to confirm our results and determine long-term effects of vegan diets on the canine gut microbiome.
Antifungal mechanism of cell-free supernatant produced by Trichoderma virens and its efficacy for the control of pear Valsa canker
Authors: Zhang Yang , Lu Ying , Jin Zhaoyang , Li Bo , Wu Li , He Yujian
Published: April 2024

Introduction

Pear Valsa canker, caused by Valsa pyri (V. pyri), poses a major threat to pear production. We aimed to assess the effectiveness of the cell-free supernatant (CFS) produced by Trichoderma virens (T. virens) to control the development of pear Valsa canker and reveal the inhibitory mechanism against the pathogenic fungi.

Results

Using morphological characteristics and phylogenetic analysis, the pathogen G1H was identified as V. pyri, and the biocontrol fungus WJ561 was identified as Trichoderma virens. CFS derived from WJ561 exhibited strong inhibition of mycelial growth and was capable of reducing the pathogenicity of V. pyri on pear leaves and twigs. Scanning electron microscopy (SEM) observations revealed deformations and shrinkages in the fungal hyphae treated with CFS. The CFS also destroyed the hyphal membranes leading to the leakage of cellular contents and an increase in the malondialdehyde (MDA) content. Additionally, CFS significantly inhibited the activities of catalase (CAT) and superoxide dismutase (SOD), and downregulated the expression of antioxidant defense-related genes in V. pyri, causing the accumulation of reactive oxygen species (ROS). Artesunate, identified as the main component in CFS by liquid chromatograph-mass spectrometry (LC–MS), exhibited antifungal activity against V. pyri.

Conclusion

Our findings demonstrate the promising potential of T. virens and its CFS in controlling pear Valsa canker. The primary inhibitory mechanism of CFS involves multiple processes, including membrane damage and negatively affecting enzymatic detoxification pathways, consequently leading to hyphal oxidative damage of V. pyri. This study lays a theoretical foundation for the utilization of T. virens to control V. pyri in practical production.
Trends in cause-specific mortality among persons with Alzheimer’s disease in South Carolina: 2014 to 2019
Authors: Brown Candace S. , Ning Xi , Money Amy , Alford Mauriah , Pan Yinghao , Miller Margaret , Lohman Matthew
Published: April 2024

Introduction

Inconsistencies of reports contributes to the underreporting of Alzheimer’s disease (AD) on death certificates. Whether underreporting exists within South Carolina has not been studied.

Methods

We conducted a prospective, population-based study on a cohort of persons (N = 78,534) previously diagnosed with AD and died between 2014–2019. We linked vital records with the South Carolina Alzheimer’s Disease and Related Dementias Registry to investigate their cause of death and survival rates. Descriptive analyses calculated frequencies of demographic and health-related characteristics. Turnbull’s method estimated the survival probabilities for different subgroups of patients. Hazard ratios were computed from the Cox proportional hazards model, adjusting for the following confounding variables of age at diagnosis, education level, gender, and race.

Results

The top immediate cause of death was Alzheimer’s disease among all racial groups, except for Native American/American Indian. More females (60.3%) were affected by AD compared to males (39.7%). There is a 25% probability of survival, beyond 5 years, after AD diagnosis. Black/African American AD patients have the smallest risk of all-cause mortality across all racial/ethnic groups (HR 0.87; 95% CI, 0.85–0.89). Individuals with lower education had a lower likelihood of mortality.

Conclusion

Although AD was not underreported in the state of South Carolina further research is needed to develop protocols around classification of deaths among those diagnosed with dementia and comorbidities, including cardiovascular disease, to ensure dementia is properly reported as we move to prevent and treat Alzheimer’s disease by 2025 and beyond.
The relationship between gender differences in dietary habits, neuroinflammation, and Alzheimer’s disease
Authors: Warren Alison
Published: April 2024

Neurocognitive decline is one of the foremost dire issues in medicine today. The mechanisms by which dementia pathogenesis ensues are complicated and multifactorial, particularly in the case of Alzheimer’s disease (AD). One irrefutable, yet unexplained factor is the gender disparity in AD, in which women are disproportionately affected by AD, both in the rate and severity of the disease. Examining the multifaceted contributing causes along with unique gender dynamics in modifiable risk factors, such as diet, may lend some insight into why this disparity exists and potential paths forward. The aim of this brief narrative review is to summarize the current literature of gender differences in dietary habits and how they may relate to neuroinflammatory states that contribute to AD pathogenesis. As such, the interplay between diet, hormones, and inflammation will be discussed, along with potential interventions to inform care practices.
Causal role of immune cell phenotypes in idiopathic sudden sensorineural hearing loss: a bi-directional Mendelian randomization study
Authors: Li Wanqing , Zhou Qiang , Zhou Linsa , Cao Longhe , Zhu Chuansai , Dai Zhijian , Lin Sen
Published: April 2024

Background

A growing body of evidence suggests that immunological processes have a significant role in developing idiopathic sudden sensorineural hearing loss (SSHL). However, few studies have examined the association between immune cell phenotype and SSHL using Mendelian Randomization (MR).

Methods

The online genome-wide association studies (GWAS) database was used to compile data from GWAS covering 731 immunophenotypes and SSHL. Inverse variance weighted (IVW) analysis was primarily used for MR study, and single nucleotide polymorphisms (SNPs) associated with immunophenotypes served as dependent variables. A sensitivity study and the false discovery rate (FDR) correction were used to examine the MR hypothesis. In addition, the possibility of reverse causality between immunophenotype and SSHL was validated by reverse MR. Reverse MR was analyzed in a manner consistent with forward MR.

Results

After FDR correction and sensitivity analysis, we screened 7 immunophenotypes, including IgD+ CD38dim %lymphocyte (95% CI: 1.0019, 1.0742, p = 3.87 × 10−2, FDR = 1.15 × 10−2); Unsw mem AC (95% CI: 1.004, 1.2522, p = 4.23 × 10−2, FDR = 2.25 × 10−2); CD86+ myeloid DC AC (95% CI: 1.0083, 1.1147, p = 2.24 × 10−2, FDR = 4.27 × 10−2); CD33dim HLA DR− AC (95% CI: 1.0046, 1.0583, p = 2.12 × 10−2, FDR = 4.69 × 10−2); SSC-A on CD8br (95% CI: 1.0028, 1.1461, p = 4.12 × 10−2, FDR = 4.71 × 10−2); CD45RA− CD4+ %T cell (95% CI: 1.0036, 1.0503, p = 2.32 × 10−2, FDR = 4.82 × 10−2); DP (CD4+CD8+) AC (95% CI: 1.011, 1.2091, p = 2.78 × 10−2, FDR = 4.97 × 10−2). There was a strong causal relationship with SSHL onset, and the reliability of the results was verified. Furthermore, the immunological cell profile and SSHL did not appear to be closely associated, as shown by reverse MR analysis.

Conclusion

Our study provides more support for the current hypothesis that immunophenotypes and the pathophysiology of SSHL are closely associated. Further validation is needed to assess the role of these immunophenotypes in SSHL.
Ewing sarcoma of the pancreas: a pediatric case report and narrative literature review
Authors: Liu Zhensheng , Bian Jian , Yang Yong , Wei Decheng , Qi Shiqin
Published: April 2024

Ewing’s Sarcoma (ES) is an rare, small round-cell sarcoma that predominantly occurs in children and young adults, with both skeletal and extraskeletal manifestations. However, pancreatic ES, due to its rarity, is infrequently featured in scholarly literature, with only a scant 43 reported instances. Our study describes a case of pancreatic ES in an 8-year-old boy who was found to have an abdominal mass. Following an exhaustive examination, the boy was diagnosed with a neoplasm in the pancreatic head and underwent a complex surgical procedure encompassing pancreatoduodenectomy and partial transverse colectomy. Immunohistochemical assays confirmed the neoplastic cells’ positivity for Cluster of Differentiation 99(CD99), Vimentin, and NK2 Homeobox 2(NKX2.2), while genomic testing identified an EWSR1-FLI1(Ewing Sarcoma Breakpoint Region 1–Friend Leukemia Integration 1) gene fusion. This led to a conclusive diagnosis of pancreatic Ewing’s Sarcoma. The patient underwent seven cycles of adjuvant chemotherapy, alternating between VDC (Vincristine, Doxorubicin, Cyclophosphamide) and IE (Ifosfamide, Etoposide) tri-weekly, but did not undergo radiotherapy. At present, the patient remains neoplasm-free. Through our case analysis and comprehensive review of the existing literature, we aim to underscore th rarity of pancreatic Ewing’s sarcoma and to highlight the efficacy of our individualized therapeutic approach.
A riboflavin transporter deficiency presenting as pure red cell aplasia: a pediatric case report
Authors: Cheng Jingying , Yao Jiafeng , Zhao Shasha , Fu Lingling , Zhang Liqiang , Jiang Jin
Published: April 2024

Introduction

Riboflavin transporter deficiency (RTD) is a rare genetic disorder that affects riboflavin transport, leading to impaired red blood cell production and resulting in pure red cell aplasia. Recognizing and understanding its clinical manifestations, diagnosis, and management is important.

Case presentation

A 2-year-old patient presented with pure red cell aplasia as the primary symptom of RTD. After confirming the diagnosis, rapid reversal of anemia was achieved after high-dose riboflavin treatment.

Conclusion

RTD often has an insidious onset, and neurological symptoms appear gradually as the disease progresses, making it prone to misdiagnosis. Genetic testing and bone marrow biopsy can confirm the diagnosis.
A physiologically based pharmacokinetic/pharmacodynamic model to determine dosage regimens and withdrawal intervals of aditoprim against Streptococcus suis
Authors: Mi Kun , Sun Lei , Zhang Lan , Tang Aoran , Tian Xiaoyuan , Hou Yixuan , Sun Lingling , Huang Lingli
Published: April 2024

Introduction: Streptococcus suis (S. suis) is a zoonotic pathogen threatening public health. Aditoprim (ADP), a novel veterinary medicine, exhibits an antibacterial effect against S. suis. In this study, a physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) model was used to determine the dosage regimens of ADP against S. suis and withdrawal intervals.

Methods: The PBPK model of ADP injection can predict drug concentrations in plasma, liver, kidney, muscle, and fat. A semi-mechanistic pharmacodynamic (PD) model, including susceptible subpopulation and resistant subpopulation, is successfully developed by a nonlinear mixed-effect model to evaluate antibacterial effects. An integrated PBPK/PD model is conducted to predict the time-course of bacterial count change and resistance development under different ADP dosages.

Results: ADP injection, administrated at 20 mg/kg with 12 intervals for 3 consecutive days, can exert an excellent antibacterial effect while avoiding resistance emergence. The withdrawal interval at the recommended dosage regimen is determined as 18 days to ensure food safety.

Discussion: This study suggests that the PBPK/PD model can be applied as an effective tool for the antibacterial effect and safety evaluation of novel veterinary drugs.
The nonvesicular sterol transporter Aster-C plays a minor role in whole body cholesterol balance
Authors: Banerjee Rakhee , Hohe Rachel C. , Cao Shijie , Jung Bryan M. , Horak Anthony J. , Ramachandiran Iyappan , Massey William J. , Varadharajan Venkateshwari , Zajczenko Natalie I. , Burrows Amy C. , Dutta Sumita , Goudarzi Maryam , Mahen Kala , Carter Abigail , Helsley Robert N. , Gordon Scott M. , Morton Richard E. , Strauch Christopher , Willard Belinda , Gogonea Camelia Baleanu , Gogonea Valentin , Pedrelli Matteo , Parini Paolo , Brown J. Mark
Published: April 2024

Introduction:

The Aster-C protein (encoded by the Gramd1c gene) is an endoplasmic reticulum (ER) resident protein that has been reported to transport cholesterol from the plasma membrane to the ER. Although there is a clear role for the closely-related Aster-B protein in cholesterol transport and downstream esterification in the adrenal gland, the specific role for Aster-C in cholesterol homeostasis is not well understood. Here, we have examined whole body cholesterol balance in mice globally lacking Aster-C under low or high dietary cholesterol conditions.

Method:

Age-matched Gramd1c+/+ and Gramd1c−/− mice were fed either low (0.02%, wt/wt) or high (0.2%, wt/wt) dietarycholesterol and levels of sterol-derived metabolites were assessed in the feces, liver, and plasma.

Results:

Compared to wild type controls (Gramd1c+/+) mice, mice lackingGramd1c (Gramd1c−/−) have no significant alterations in fecal, liver, or plasma cholesterol. Given the potential role for Aster C in modulating cholesterol metabolism in diverse tissues, we quantified levels of cholesterol metabolites such as bile acids, oxysterols, and steroid hormones. Compared to Gramd1c+/+ controls, Gramd1c−/− mice had modestly reduced levels of select bile acid species and elevated cortisol levels, only under low dietary cholesterol conditions. However, the vast majority of bile acids, oxysterols, and steroid hormones were unaltered in Gramd1c−/− mice. Bulk RNA sequencing in the liver showed that Gramd1c−/− mice did not exhibit alterations in sterol-sensitive genes, but instead showed altered expression of genes in major urinary protein and cytochrome P450 (CYP) families only under low dietary cholesterol conditions.

Discussion:

Collectively, these data indicate nominal effects of Aster-C on whole body cholesterol transport and metabolism under divergent dietary cholesterol conditions. These results strongly suggest that Aster-C alone is not sufficient to control whole body cholesterol balance, but can modestly impact circulating cortisol and bile acid levels when dietary cholesterol is limited.