bluuebunny/crossref_metadata_2025 huggingface dataset:
ANALISIS OPTIMISASI DENGAN MENGGUNAKAN METODE GOAL PROGRAMMING TANPA PRIORITAS TERHADAP LAPORAN KEUANGAN BANK (STUDI KASUS: PT BANK NATIONAL NOBU TBK)
Authors: Haikal Fahri Muhammad , Wijayanti Hagni , Kamila Isti
Published: May 2024

Periodically, Nobu Bank releases an annual financial report that describes the company's financial condition. The financial statements contain elements of financial statements, namely assets, liabilities, equity, income, and financial expenses. To analyze the optimization, the five elements of the financial statements are then expressed in a mathematical model as a constraint function to be processed using the Goal Programming Method. The Goal Programming method was chosen because it is considered a mathematical model that can be used to obtain solutions to problems that have many goals. After all, the deviation variable in the Goal Programming model can produce complete information on the relative achievement of existing goals so that optimal results can be achieved. The first step of the Goal Programming Method is to determine the decision variables, then determine the objective function, then determine the constraint function. The analysis and solution were carried out using the Simplex Method and validated with the LINGO. The results of the sensitivity analysis show that the five objectives have been achieved, namely, there are no deviations. This shows that the performance of the financial statements at Bank Nobu is optimal. However, two objectives can still be optimized, such as the value of liabilities can still be reduced by Rp.593,731.14 per year, and the value of financial expenses can still be reduced by Rp.30,599.66 per year.
ANALISIS STRATEGI PEMASARAN DALAM PERSAINGAN PERUSAHAAN MARKETPLACE ANTARA TOKOPEDIA, SHOPEE, DAN LAZADA MENGGUNAKAN GAME THEORY
Authors: Amelia Rika , Wijayanti Hagni , Widyastiti Maya
Published: May 2024

Perkembangan teknologi dan kemajuan ekonomi pada era digital 4.0 menyebabkanmeningkatnya persaingan antara perusahaan untuk memperebutkan komsumen. Jenis eï¿¾commerce berkembang di Indonesia adalah marketplace. Marketplace perlu melakukanpenyusunan strategi untuk memenangkan persaingan pasar, strategi tersebut dapat ditentukanmelalui konsep game theory dengan metode simpleks. Tujuan dari penelitian ini yaitumenentukan atribut strategi pemasaran yang optimal khusus perusahaan Tokopedia, Shopee, danstudi kasus penduduk di wilayah Kecamatan Cileungsi.Pengambilan data menggunakan dataprimer dengan menyebarkan kuesioner online dan menggunakan teknik non-probability samplingyaitu accidental sampling, karena dengan kondisi pandemi ini sulit untuk bertemu langsungdengan responden, sehingga seseorang yang diambil sebagai sampel dalam penelitianberdasarkan faktor spontanitas atau seseorang tersebut melihat status di media sosial penulisdan menganggap bahwa seseorang tersebut memiliki informasi yang sesuai dengan karakteristikyang diperlukan bagi penelitian. Alternatif strategi pemasaran yang digunakan yaitu harga,kualitas produk, keamanan, tampilan desain, ketersediaan ekspedisi, promo dan kelengkapanfasilitas. Hasil strategi optimal khusus Shopee adalah strategi promo, kelengkapan fasilitas,tampilan desain dan keamanan. Strategi optimal untuk Tokopedia yaitu strategi keamanan,harga, promo, ketersediaan expedisi. Sedangkan perusahaan Lazada strategi optimalnya ialahstrategi kelengkapan fasilitas, ketersediaan ekspedisi, promo dan tampilan desain
METODE QUADRATIC SPLINE DAN HELIGMAN-POLLARD DALAM PENYUSUNAN LIFE TABLE DESA GEGELANG LOMBOK BARAT
Authors: Fauzi Andri Azmul , Nugrahani Endar Hafasah , Sumarno Hadi
Published: May 2024

In this paper, we conduct research by compiling an  abridged life table using the graduation method based on real data obtained at Gegelang Village, West Lombok. The graduation method used in this study included quadratic spline and Heligman-Pollard. Based on the results, a special case of A-method was chosen as a method used to make a rough life table before graduation. After graduation process, it was found that the most suitable method was the Heligman-Pollard method. This is based on the graph produced using this method which is monotonous in nature, not fluctuating like other graduation methods. In addition, life expectancy obtained at 65,72 years is close to West Lombok's life expectancy based on 2015.
ANALISIS PENGARUH FAKTOR RISIKO PENYAKIT PNEUMONIA TERHADAP ANGKA MORTALITAS BAYI DAN BALITA MENGGUNAKAN REGRESI POISSON DAN REGRESI BINOMIAL NEGATIF (Studi Kasus : Provinsi Jawa Barat)
Authors: Nursantika Maulida , Faridhan Yasmin Erika , Kamila Isti
Published: May 2024

Pneumonia is an acute infectious disease that attacks lungs caused by viruses, bacteria or fungi. This infection can be life-threatening for anyone, especially infants, children and people aged 65 years. In 2020 in West Java Province infant and toddler deaths due to pneumonia reached 122 cases. This study aims to analyze the factors that influence infant and under-five mortality rates by comparing Poisson regression and negative binomial regression, as well as modeling significant factors. The handling of overdispersion cases in Poisson regression can be done with alternative methods, one of which is the negative binomial regression method. This study uses secondary data obtained from the Health Profile of West Java Province 2020. The results of the study show that negative binomial regression handles overdispersion cases in data on the number of infant and under-five deaths due to pneumonia in West Java Province in 2020. Factors that influence infant mortality rates and toddlers due to pneumonia are low birth weight babies (X2) and population density (X4).
Theological and Ethical Perspectives on Rethinking the Co-existence of Flourishing and Vulnerability
Authors: Vuk Martina
Published: May 2024

The aim of this article is to explore the evolving discussion surrounding vulnerability and flourishing. This conversation has gained significant relevance in the aftermath of the COVID-19 pandemic and amid global uncertainties, including the effects of violence and war-trauma. The central idea here is to reconsider vulnerability and flourishing not simply as universal experiences tied to one's own humanity and social context, but rather as co-existing, interdependent, and contingent aspects of human existence. Without proposing that human flourishing is conditioned by vulnerability, this perspective seeks to challenge the notion that vulnerability and flourishing are fundamentally separate. The following discussion will not only examine vulnerability and flourishing as theoretical concepts but will also address their practical significance as integral components of the human experience, and how they intersect in a real-life situation. It's important to note that both vulnerability and flourishing are influenced by specific contexts and circumstances, including personal, social, economic and cultural factors. In the course of this discussion, I will provide examples to illustrate these points. The first section will focus on vulnerability, while the second will delve into the concept of flourishing from a Christian perspective, drawing on Miroslav Volf's ideas about a flourishing life.
Overcoming vulnerability by editing the germline?
Authors: Braunschweig Michael
Published: May 2024

The concept of vulnerability has become widely acknowledged as a fundamental concept for medical ethics and research ethics, yet rarely considered with respect to ethical assessments of human germline genome editing. A first aim of this paper is to make vulnerability ethics considerations fruitful for issues related to these technical innovations. The possibility of altering the genome promises to overcome forms of vulnerability inherently connected to our existence as physical beings and would hence allow to increase the resilience of human nature or even to move evolution forward by equipping people with new character traits and enhanced capabilities. I suggest a more fine-grained distinction of various applications purposes than the dichotomy of therapeutic and enhancement. I support the rejection of most application purposes as ‘therapeutic’ and claim that framing them as ‘therapeutic’ in the context of the current discursive constellation runs the risk of accentuating existing vulnerabilities. With respect to intergenerational responsibilities, I reject the view that editing the germline necessarily leads to corrupt intergenerational relations based on which it must be categorically excluded. I conclude that it is nevertheless important to take a very close look at the challenges that arise, especially from a vulnerability perspective, before irreversible facts are created overhastily.
PERANCANGAN SISTEM INFORMASI PENJUALAN RUMAH BERBASIS WEB PADA PT.AGUNG SELARAS GROUP PEKANBARU
Authors: Rahmaddion Armiza , Arrribe Edo
Published: May 2024

In the current digital era, a housing sales information system is a crucial component in the operations of property companies. The use of web-based information technology has become a necessity to enhance efficiency and expand market reach. Therefore, this research aims to design and develop a web-based housing sales information system for PT. Agung Selaras Group Pekanbaru. The research methodology includes analysis, system design, implementation, and testing phases. The result of this research is a web-based housing sales information system that can assist PT. Agung Selaras Group Pekanbaru in efficiently managing the housing sales process. This system is equipped with features such as detailed housing information, housing search based on specific criteria, booking processes, and online payments. Additionally, the system allows users to view housing photo galleries, obtain contact information, and provide reviews for the purchased houses.
ANALISA USABILITY PADA APLIKASI HUMAN RESOURCE HIRA MENGGUNAKAN METODE SYSTEM USABILITY SCALE DAN USE QUESTIONNAIRE
Authors: Karista Kafka Titania , Badrul Mohammad
Published: May 2024

In facing the challenges of human resource management (HR) in a competitive business era, many organizations are adopting Human Resource Hira applications to support workforce management. This research was conducted to analyze Hira's usability using the System Usability Scale (SUS) and Use Questionnaire methods. The background to the problem involves user complaints regarding the quality of Hira, such as loading that takes quite a long time when logging in, locations that often have errors when checking in, the pay slip feature that often does not appear, etc. This research aims to identify Hira usability evaluations and provide recommendations for improvements. The results of usability analysis using SUS show a decent level of usability, with an average score of 51.09. Meanwhile the results of the USE Questionnaire also indicate a very good level of usability, with an average score of 91%. Thus, this research contributes to the understanding that Hira has a high level of usability, creates a satisfying user experience, and meets organizational operational needs. Improvement recommendations are not required based on the results of this positive usability evaluation.
Oral administration of a new copper (I) complex with coumarin as ligand: modulation of the immune response and the composition of the intestinal microbiota in Onchorhynchus mykiss
Authors: Parra Mick , Aldabaldetrecu Maialen , Arce Pablo , Soto-Aguilera Sarita , Vargas Rodrigo , Guerrero Juan , Tello Mario , Modak Brenda
Published: May 2024

[Cu(NN1)2]ClO4 is a copper (I) complex, where NN1 is an imine ligand 6-((quinolin-2-ylmethylene) amino)-2H-chromen-2-one obtained by derivatization of natural compound coumarin, developed for the treatment of infectious diseases that affect salmonids. In previous research, we showed that the Cu(I) coordination complex possesses antibacterial activity against Flavobacterium psychrophilum, providing protection against this pathogen in rainbow trout during challenge assays (with an RPS of 50%). In the present study, the effects of administering [Cu(NN1)2]ClO4 to Oncorhynchus mykiss over a 60-days period were evaluated with regard to systemic immune response and its potential to alter intestinal microbiota composition. In O. mykiss, an immunostimulatory effect was evident at days 30 and 45 after administration, resulting in an increment of transcript levels of IFN-γ, IL-12, TNF-α, lysozyme and perforin. To determine whether these immunomodulatory effects correlated with changes in the intestinal microbiota, we analyzed the metagenome diversity by V4 16S rRNA sequencing. In O. mykiss, both [Cu(NN1)2]ClO4 and commercial antibiotic florfenicol had comparable effects at the phylum level, resulting in a predominance of proteobacteria and firmicutes. Nonetheless, at the genus level, florfenicol and [Cu(NN1)2]ClO4 complex exhibited distinct effects on the intestinal microbiota of O. mykiss. In conclusion, our findings demonstrate that [Cu(NN1)2]ClO4 is capable of stimulating the immune system at a systemic level, while inducing alterations in the composition of the intestinal microbiota in O. mykiss.
Characterization of Neisseria gonorrhoeae colonization of macrophages under distinct polarization states and nutrients environment
Authors: Juárez Rodríguez María Dolores , Marquette Madison , Youngblood Reneau , Dhungel Nilu , Torres Escobar Ascención , Ivanov Stanimir S. , Dragoi Ana-Maria
Published: May 2024

Neisseria gonorrhoeae (Ng) is a uniquely adapted human pathogen and the etiological agent of gonorrhea, a sexually transmitted disease. Ng has developed numerous mechanisms to avoid and actively suppress innate and adaptive immune responses. Ng successfully colonizes and establishes topologically distinct colonies in human macrophages and avoids phagocytic killing. During colonization, Ng manipulates the actin cytoskeleton to invade and create an intracellular niche supportive of bacterial replication. The cellular reservoir(s) supporting bacterial replication and persistence in gonorrhea infections are poorly defined. The manner in which gonococci colonize macrophages points to this innate immune phagocyte as a strong candidate for a cellular niche during natural infection. Here we investigate whether nutrients availability and immunological polarization alter macrophage colonization by Ng. Differentiation of macrophages in pro-inflammatory (M1-like) and tolerogenic (M2-like) phenotypes prior to infection reveals that Ng can invade macrophages in all activation states, albeit with lower efficiency in M1-like macrophages. These results suggest that during natural infection, bacteria could invade and grow within macrophages regardless of the nutrients availability and the macrophage immune activation status.
Arrhythmia monitoring and outcome after myocardial infarction (BIO|GUARD-MI): a randomized trial
Authors: Jøns Christian , Bloch Thomsen Poul Erik , Riahi Sam , Smilde Tom , Bach Ulrich , Jacobsen Peter Karl , Táborský Miloš , Faluközy Jozsef , Wiemer Marcus , Christensen Per Dahl , Kónyi Attila , Schelfaut Dan , Bulava Alan , Grabowski Marcin , Merkely Béla , Nuyens Dieter , Mahajan Rajiv , Nagel Patrick , Tilz Roland , Malczynski Jerzy , Steinwender Clemens , Brachmann Johannes , Serota Harvey , Schrader Jürgen , Behrens Steffen , Søgaard Peter
Published: May 2024

Objectives

Cardiac arrhythmias predict poor outcome after myocardial infarction (MI). We studied if arrhythmia monitoring with an insertable cardiac monitor (ICM) can improve treatment and outcome.

Design

BIO|GUARD-MI was a randomized, international open-label study with blinded outcome assessment.

Setting

Tertiary care facilities monitored the arrhythmias, while the follow-up remained with primary care physicians.

Participants

Patients after ST-elevation (STEMI) or non-ST-elevation MI with an ejection fraction >35% and a CHA2DS2-VASc score ≥4 (men) or ≥5 (women).

Interventions

Patients were randomly assigned to receive or not receive an ICM in addition to standard post-MI treatment. Device-detected arrhythmias triggered immediate guideline recommended therapy changes via remote monitoring.

Main outcome measures

MACE, defined as a composite of cardiovascular death or acute unscheduled hospitalization for cardiovascular causes.

Results

790 patients (mean age 71 years, 72% male, 51% non-STEMI) of planned 1,400 pts were enrolled and followed for a median of 31.6 months. At 2 years, 39.4% of the device group and 6.7% of the control group had their therapy adapted for an arrhythmia [hazard ratio (HR) = 5.9, P < 0.0001]. Most frequent arrhythmias were atrial fibrillation, pauses and bradycardia. The use of an ICM did not improve outcome in the entire cohort (HR = 0.84, 95%-CI: 0.65–1.10; P = 0.21). In secondary analysis, a statistically significant interaction of the type of infarction suggests a benefit in the pre-specified non-STEMI subgroup. Risk factor analysis indicates that this may be connected to the higher incidence of MACE in patients with non-STEMI.

Conclusions

The burden of asymptomatic but actionable arrhythmias is large in post-infarction patients. However, arrhythmia monitoring with an ICM did not improve outcome in the entire cohort. Post-hoc analysis suggests that it may be beneficial in non-STEMI patients or other high-risk subgroups.

Clinical Trial Registration

[https://www.clinicaltrials.gov/ct2/show/NCT02341534], NCT02341534.
Understanding older people's voice interactions with smart voice assistants: a new modified rule-based natural language processing model with human input
Authors: Yan Zhengxu , Dube Victoria , Heselton Judith , Johnson Kate , Yan Changmin , Jones Valerie , Blaskewicz Boron Julie , Shade Marcia
Published: May 2024

The COVID-19 pandemic has expedited the integration of Smart Voice Assistants (SVA) among older people. The qualitative data derived from user commands on SVA is pivotal for elucidating the engagement patterns of older individuals with such systems. However, the sheer volume of user-generated voice interaction data presents a formidable challenge for manual coding. Compounding this issue, age-related cognitive decline and alterations in speech patterns further complicate the interpretation of older users’ SVA voice interactions. Conventional dictionary-based textual analysis tools, which count word frequencies, are inadequate in capturing the evolving and communicative essence of these interactions that unfold over a series of dialogues and modify with time. To address these challenges, our study introduces a novel, modified rule-based Natural Language Processing (MR-NLP) model augmented with human input. This reproducible approach capitalizes on human-derived insights to establish a lexicon of critical keywords and to formulate rules for the iterative refinement of the NLP model. English speakers, aged 50 or older and residing alone, were enlisted to engage with Amazon Alexa™ via predefined daily routines for a minimum of 30 min daily spanning three months (N = 35, mean age = 77). We amassed time-stamped, textual data comprising participants’ user commands and responses from Alexa™. Initially, a subset constituting 20% of the data (1,020 instances) underwent manual coding by human coder, predicated on keywords and commands. Separately, a rule-based Natural Language Processing (NLP) methodology was employed to code the identical subset. Discrepancies arising between human coder and the NLP model programmer were deliberated upon and reconciled to refine the rule-based NLP coding framework for the entire dataset. The modified rule-based NLP approach demonstrated notable enhancements in efficiency and scalability and reduced susceptibility to inadvertent errors in comparison to manual coding. Furthermore, human input was instrumental in augmenting the NLP model, yielding insights germane to the aging adult demographic, such as recurring speech patterns or ambiguities. By disseminating this innovative software solution to the scientific community, we endeavor to advance research and innovation in NLP model formulation, subsequently contributing to the understanding of older people's interactions with SVA and other AI-powered systems.
‘Love, Love not’—a discovery of study engagement at higher education and the factors involved
Authors: Nguyen Trang Thi Nhu , Bui Thai Thi Hong , Nguyen Lan Thi , Dao Hang Thuy , Nguyen Nguyen Lan , Mai Hanh Tuyet , Nguyen Ha Thi Thu
Published: May 2024

Taking that higher education is career-oriented, this study examines how Vietnamese undergraduate students engage with their study and how the factors related to the training program and occupation’s prospects contribute to students’ engagement with their study. The study applies a mixed-method approach. Self-administered questionnaire survey is used to collect data from 973 Vietnamese undergraduate students, of which 48.2% are social work students and 51.8% are non-social work students. In addition, the study conducts 27 semi-structured interviews with students and lecturers to explore their perspective and experiences with regard to students’ study engagement and the factors involved. The results show that social work students are more engaged with their study than non-social work students, even though they feel more worried about job opportunity and income. Approximately one-third of social work students consider not to pursue social work profession when they graduate mostly because they believe that working in social work cannot provide them the income they need for their living. However, the results also show that students’ satisfaction/dissatisfaction with income in their field was not statistically related to their study engagement. Instead, feeling of personal growth, opportunity to perform personal ability, sense of significance, convenient access to study materials and activities, and feeling proud of their school and lecturers’ prestige are found positively associated with students’ level of study engagement. The study hence provides some recommendations for educators to strengthen students’ study engagement at higher education level.
The predictive value of free thyroxine combined with tubular atrophy/interstitial fibrosis for poor prognosis in patients with IgA nephropathy
Authors: Yang Bixia , Zhou Wen , Cui Liqin , Tian Li , Ni Yanhong , Yang Min , Yang Yan
Published: May 2024

Background

IgA nephropathy (IgAN), the most common type of glomerulonephritis, has great individual differences in prognosis. Many studies showed the relationship between thyroid hormones and chronic kidney disease. However, the relationship between free thyroxine (FT4), as a thyroid hormone, and IgAN is still unclear. This study aimed to evaluate the impact of FT4 on IgAN prognosis.

Methods

This retrospective study involved 223 patients with biopsy-proven IgAN. The renal composite outcomes were defined as: (1) ESRD, defined as eGFR < 15 ml/(min·1.73 m2) or initiation of renal replacement therapy (hemodialysis, peritoneal dialysis, renal transplantation); (2) serum creatinine doubled from baseline; (3) eGFR decreased by more than 50% from baseline. The predictive value was determined by the area under the curve (AUC). Kaplan-Meier and Cox proportional hazards analyses assessed renal progression and prognosis.

Results

After 38 (26–54) months of follow-up, 23 patients (10.3%) experienced renal composite outcomes. Kaplan-Meier survival curve analysis showed that the renal survival rate of the IgAN patients with FT4<15.18pmol/L was lower than that with FT4≥15.18pmol/L (P < 0. 001). Multivariate Cox regression model analysis showed that FT4 was a protective factor for poor prognosis of IgAN patients, whether as a continuous variable or a categorical variable (HR 0.68, 95%CI 0.51–0.90, P =0.007; HR 0.04, 95%CI 0.01–0.20, P <0.001). ROC curve analysis showed that FT4 combined with t score had a high predictive value for poor prognosis of IgAN patients (AUC=0.881, P<0.001).

Conclusion

FT4 was a protective factor for IgAN. In addition, FT4 combined with tubular atrophy/interstitial fibrosis had a high predictive value for poor prognosis of IgAN.
Correlation between vessel density and thickness in the retina and choroid of severe non-proliferative diabetic retinopathy patients
Authors: He Kai , Wei-Zhang Selena , Li Ziqi , Kaysar Parhat , Yang Tianjing , Sun Zhiyong , Zhou Wei , Yan Hua
Published: May 2024

Objectives

To explore the correlation between the vessel density (VD) of the retina and choroid vascular plexuses and the thicknesses of their respective retinal layers and choroid membranes in participants with severe non-proliferative diabetic retinopathy (NPDR).

Methods

We retrospectively analyzed the data of 42 eyes of 42 participants with diabetes mellitus (DM) and severe NPDR. In addition, 41 eyes of 41 healthy controls were evaluated. Measurements were taken for both groups using optical coherence tomography angiography (OCTA), including the area and perimeter of the foveal vascular zone (FAZ) and the vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choroid capillary (CC). These measurements were compared with the retinal thickness (RT) of the inner/intermediate retinal layers and choroidal thickness (CT). The study evaluated the correlation between RT or CT and VD in the respective vascular networks, namely superficial capillary plexus (SCP), deep capillary plexus (DCP), or CC.

Results

The inner RT and VD in all plexuses were significantly lower in the severe NPDR group than in the healthy controls. Furthermore, the FAZ area and perimeter were larger in the severe NPDR group. Inner RT was correlated with VD in the SCP group (r=0.67 and r=0.71 in the healthy control and severe NPDR groups, respectively; p<0.05). CT negatively correlated with VD in the CC (r=-0.697 and r=-0.759 in the healthy control and severe NPDR groups, respectively; p<0.05). Intermediate RT significantly correlated with VD in the DCP of the severe NPDR group (r=-0.55, p<0.05), but not in the healthy control group.

Conclusions

Retinal or choroidal thickness strongly correlated with VD. Therefore, patients with severe NPDR must consider the distinct anatomical and functional entities of the various retinal layers and the choroid.
Influence of maximum diameter on fine-needle aspiration biopsy outcomes in ACR TI-RADS 5 thyroid nodules
Authors: Cao Shi-Liang , Shi Wan-Ying , Niu Yi-Ru , Zhao Zhen-Long , Wei Ying , Wu Jie , Peng Li-Li , Li Yan , Yu Ming-An
Published: May 2024

Introduction

Fine needle aspiration (FNA) biopsy is a widely accepted method for diagnosing thyroid nodules. However, the influence of maximum diameter (MD) of ACR TIRADS 5 (TR5) thyroid nodules on the FNA outcomes remains debated. This study examined the influence of MD on the FNA outcomes and investigated the optimal MD threshold for FNA in TR5 nodules.

Methods

We conducted a retrospective analysis of 280 TR5 thyroid nodules from 226 patients who underwent FNA from January to June 2022 in our department. Probably malignant (PM) group was defined as Bethesda V in cytopathology with confirmed BRAF V600E mutation or Bethesda VI, the other cytopathology outcomes were defined as probably benign (PB) group. We examined factors influencing malignant cytopathology outcomes and determined the optimal MD threshold for FNA in TR5 nodules using logistic regression and restricted cubic spline (RCS) analysis.

Results

Among these nodules, 58.2% (163/280) had PM outcomes. The PM group had a significantly larger MD than the PB group [6.5mm (range 5.0-8.4) vs. 5.3mm (range 4.0-7.0), p < 0.001]. In multivariate logistic regression fully adjusted for confounders, MD was significantly associated with PM outcomes [odds ratio 1.16, 95%CI 1.05-1.31; p = 0.042]. The highest quartile of MD had a greater likelihood of PM outcomes compared to the lowest quartile [odds ratio 4.71, 95% CI 1.97-11.69, p = 0.001]. The RCS analysis identified 6.2 mm as the optimal MD threshold for FNA in TR5 nodules.

Conclusion

MD significantly affects the probability of malignant outcomes in FNA of TR5 thyroid nodules. A MD threshold of ≥6.2mm is suggested for FNA in these nodules.
Incorporating leys in arable systems as a mitigation strategy to reduce soil organic carbon losses during land-use change
Authors: Nyameasem John Kormla , De Los Rios Josue , Kluß Christof , Reinsch Thorsten , Poyda Arne , Taube Friedhelm , Loges Ralf
Published: May 2024

The intensification of dairy and biogas production in Northwestern Europe has led to the conversion of permanent grasslands to arable land, mainly for silage maize production, resulting in significant soil organic carbon (SOC) losses, highlighting the need for implementing alternative management practices during land use change (LUC) for effective climate change mitigation. This study evaluated the impact of incorporating annual grass-clover leys in 3-year arable rotations and slurry application to mitigate SOC losses during LUC. We compared this approach to a continuous silage maize and a permanent grassland on sandy loam soil in Northern Germany. The experiments were simultaneously established at two adjacent 17-year-old sites of permanent grassland and arable cropping, with different levels of initial SOC when the experiment was established. The SOC dynamics in the upper soil layer (0–30 cm) were evaluated by annual 12-year sampling (2011–2022). The cropping systems were unfertilized (N0) or fertilized (N1) using cattle slurry at a rate of 240 kg N ha-1 year-1. The study reveals substantial SOC losses following the conversion of the permanent grassland to grass-clover (ley) based rotation or continuous silage maize, with reductions of 22% and 31%, respectively, compared to baseline levels of the permanent grassland. However, over the 12-year period, the grass-clover ley-based crop rotation demonstrated a 30% reduction in SOC losses compared to continuous silage maize, without compromising dry matter yield. Conversely, the conversion of arable land to grasslands led to SOC increases ranging from 10% to 30%. This recovery was only half the SOC losses observed in the grassland conversion for the same period, indicating a slow-in, fast-out effect during LUC. However, the transition from ley-containing forage rotation to continuous silage maize incurred significant SOC losses of 11%. Overall, these findings underscore the imperative of integrating ley phases to mitigate SOC losses, particularly in high-biomass-yield cropping systems. As a 1-year ley phase was insufficient to sustain carbon sequestration in arable crop rotations, extended ley residence times should be considered.
Comprehensive analysis of differential long non-coding RNA and messenger RNA expression in cholelithiasis using high-throughput sequencing and bioinformatics
Authors: Sun Yanbo , Xu Conghui , Luo Jing , Li Shumin , Chen Shi , Cen Yunyun , Xu Pengyuan
Published: May 2024

Background

The etiology of gallstone disease (GSD) has not been fully elucidated. Consequently, the primary objective of this study was to scrutinize and provisionally authenticate the distinctive expression profiles of long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) in GSD.

Methods

RiboNucleic Acid (RNA) sequencing was used on four paired human gallbladder samples for the purpose of this study. Differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were identified and subjected to analysis of their biological functions. The Pearson’s correlation coefficients between DElncRNAs and DEmRNAs were computed to construct a co-expression network delineating their associations. Furthermore, both cis- and trans-regulatory networks of selected lncRNAs were established and visualized. Additionally, a competing endogenous RNA (ceRNA) regulatory network was constructed. To validate the RNA-sequencing data, we performed a Quantitative Real-time Polymerase Chain Reaction (RT-qPCR) on 10 paired human gallbladder samples, assessing the expressions of the top 4 DEmRNAs and DElncRNAs in gallstone and control samples.

Results

A total of 934 DEmRNAs and 304DElncRNAs were successfully identified. Functional enrichment analysis indicated a predominant involvement in metabolic-related biological functions. Correlation analysis revealed a strong association between the expressions of 597 DEmRNAs and 194 DElncRNAs. Subsequently, both a cis-lncRNA-mRNA and a trans-lncRNA-Transcription Factor (TF)-mRNA regulatory network were meticulously constructed. Additionally, a ceRNA network, comprising of 24 DElncRNAs, 201 DEmRNAs, and 120 predicted miRNAs, was established. Furthermore, using RT-qPCR, we observed significant upregulation of AC004692.4, HECW1-IT1, SFRP4, and COMP, while LINC01564, SLC26A3, RP1-27K12.2, and GSTA2 exhibited marked downregulation in gallstone samples. Importantly, these findings were consistent with the sequencing.

Conclusion

We conducted a screening process to identify DElncRNAs and DEmRNAs in GSD. This approach contributes to a deeper understanding of the genetic factors involved in the etiology of gallstones.
Integrated analysis of muscle transcriptome, miRNA, and proteome of Chinese indigenous breed Ningxiang pig in three developmental stages
Authors: Chen Wenwu , Xiao Yu , Yang Fang , Liufu Sui , Gong Yan , Li Zhi , Zhang Shuo , Tang Shengguo , Li Biao , Ma Haiming
Published: May 2024

The Ningxiang pig, a distinguished local breed in China, is recognized for its good meat quality traits. This study examines the proteomics of Ningxiang pigs at three developmental stages and delves into the upstream transcriptomics of these proteomics. Such an analysis facilitates a deeper understanding of the molecular interplay between proteins and transcriptomes in the Ningxiang pig muscle, influencing muscle growth and development. In this research, we analyzed the muscles of Ningxiang pigs at three developmental stages: 30 days in weaned piglets, 90 days in nursery pigs, and 210 days in late fattening pigs. There a total of 16 differentially co-expressed miRNAs (ssc-miRNA-1, ssc-miRNA-378, ssc-miRNA-143, ssc-miRNA-30e, etc.), 74 differentially co-expressed mRNA (PLIN3, CPT2, IGF2 and HSP90AB1, etc.) have been identified in the three stages. 572 differentially abundant proteins (DAPs) (APOC3, NDUFA2, HSPD1, ATP5E, PDHA1, etc.) were readily identified by comparing different time periods. According to the KEGG enrich pathway results that DAPs most enriched in growth and development pathways, immune mechanism pathways and maintaining functions of physical. Through short time-series expression miner (STEM) association analysis, a total of 571 negative miRNA-mRNA interaction pairs and 2 negative miRNA-mRNA-protein (Chr05_11955-Pig.17268.1-ATP5F1B, ssc-miR-194a-3p-Pig.15802.1-ACY1) interaction pairs were found. Our study provides a theoretical basis on molecular mechanism for the study of IMF deposition, muscle growth and immunity in Ningxiang pig breed.
A whole-exome sequencing study of patent foramen ovale: investigating genetic variants and their association with cardiovascular disorders
Authors: Li Xinyi , Xie Lingling , Dai Jin , Zhou Xinbin , Chen Tingting , Mao Wei
Published: May 2024

Background

Patent foramen ovale (PFO) has a genetic predisposition and is closely associated with cryptogenic stroke (CS), migraine, decompression sickness, and hypoxemia. Identifying PFO-related mutant genes through whole-exome sequencing (WES) can help in the early recognition of cardiovascular genetic risk factors, guide timely clinical intervention, and reduce the occurrence of cardiovascular events.

Methods

We analyzed mutant genes from ClinVar and OMIM databases. WES was performed on 25 PFO patients from Zhejiang Provincial Hospital of Chinese Medicine. Pathogenicity of variants was evaluated using American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology. (AMP) guidelines.

Results

In ClinVar (4 Feb 2023), 113 coding gene mutations were found, including 83 associated with PFO. From OMIM (18 Apr 2023), 184 gene mutations were analyzed, with 110 mutant coding genes. WES identified pathogenic mutations in two of 25 PFO patients (8%). LDLR, SDHC, and NKX2-5 genes were linked to PFO and primarily involved in myocardial tissue function. NKX2-5 may play a crucial role in PFO development, interacting with NOTCH1, GATA4, MYH6, SCN5A signaling pathways regulating cardiomyocyte characteristics.

Conclusion

We identified pathogenic mutations in LDLR, SDHC, and NKX2-5 genes, implying their role in PFO development. Functional enrichment analysis revealed NKX2-5’s interaction with signaling pathways regulating cardiomyocyte function. These findings enhance our understanding of PFO’s genetic basis, suggesting potential therapeutic targets for future research.
Development and verification of a manganese metabolism- and immune-related genes signature for prediction of prognosis and immune landscape in gastric cancer
Authors: Han Xiaoxi , Leng Chuanyu , Zhao Shufen , Wang Shasha , Chen Shuming , Wang Shibo , Zhang Mengqi , Li Xiangxue , Lu Yangyang , Wang Bing , Qi Weiwei
Published: May 2024

Background

Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body’s anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors.

Methods

Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of NPR3 in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments.

Results

GC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. NPR3 expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of NPR3 was distributed in endothelial cells. Cellular experiments demonstrated that NPR3 facilitated the proliferation of GC cells.

Conclusion

This is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.
Regulation of Treg cells by cytokine signaling and co-stimulatory molecules
Authors: Zong Yuan , Deng Kaihang , Chong Wai Po
Published: May 2024

CD4+CD25+Foxp3+ regulatory T cells (Tregs), a vital component of the immune system, are responsible for maintaining immune homeostasis and preventing excessive immune responses. This review explores the signaling pathways of the cytokines that regulate Treg cells, including transforming growth factor beta (TGF-β), interleukin (IL)-2, IL-10, and IL-35, which foster the differentiation and enhance the immunosuppressive capabilities of Tregs. It also examines how, conversely, signals mediated by IL-6 and tumor necrosis factor -alpha (TNF-α) can undermine Treg suppressive functions or even drive their reprogramming into effector T cells. The B7 family comprises indispensable co-stimulators for T cell activation. Among its members, this review focuses on the capacity of CTLA-4 and PD-1 to regulate the differentiation, function, and survival of Tregs. As Tregs play an essential role in maintaining immune homeostasis, their dysfunction contributes to the pathogenesis of autoimmune diseases. This review delves into the potential of employing Treg-based immunotherapy for the treatment of autoimmune diseases, transplant rejection, and cancer. By shedding light on these topics, this article aims to enhance our understanding of the regulation of Tregs by cytokines and their therapeutic potential for various pathological conditions.
Serum NfL and EGFR/NfL ratio mRNAs as biomarkers for phenotype and disease severity of myelin oligodendrocyte glycoprotein IgG-associated disease
Authors: Wang Xin , Qu Yi , Fan Jiayu , Ren Huiqiang
Published: May 2024

Background and purpose

Myelin oligodendrocyte glycoprotein (MOG) IgG is frequently elevated in pediatric patients with acquired demyelinating syndrome (ADS). However, no specific biomarkers exist for phenotype classification, symptom severity, prognosis, and treatment guidance of MOG-IgG-associated disease (MOGAD). This study evaluated neurofilament light chain (NfL) and endothelial growth factor receptor (EGFR) mRNA expression levels in serum and cerebrospinal fluid (CSF) as potential biomarkers for MOGAD in Chinese children.

Methods

This was a cross-sectional and single-center study. We enrolled 22 consecutive pediatric patients hospitalized with MOGAD and 20 control pediatric patients hospitalized for noninflammatory neurological diseases in Hebei Children’s Hospital. Serum and CSF were collected from MOGAD patients within 3 days before immunotherapy. The mRNA levels of NfL and EGFR in serum and CSF were measured by real-time polymerase chain reaction (qPCR), and the EGFR/NfL ratio mRNA was calculated. These measurement values were then compared between disease groups and among MOGAD phenotypes. In addition, the correlations between the mRNAs of three markers (NfL, EGFR, EGFR/NfL ratio), extended disability status scale (EDSS) scores, and clinical phenotypes were analyzed.

Results

Serum and CSF NfL mRNA levels were significantly higher of acute-stage MOGAD patients than those of control patients (p< 0.05 and p< 0.01, respectively), while the mRNA levels of serum EGFR and EGFR/NfL ratio were significantly lower of MOGAD patients than those of controls (p < 0.05, p < 0.0001). Serum NfL mRNA was significantly correlated with mRNA of serum EGFR (r =0.480, p < 0.05). Serum and CSF NfL mRNA levels in MOGAD patients with the ADEM-like phenotype were also significantly higher than those in control patients (p < 0.01, p < 0.01) and optic neuritis (ON) phenotype (p < 0.05, p < 0.05). Both mRNAs of NfL in CSF and EGFR/NfL ratio in serum were correlated with EDSS scores (p < 0.05, r = 0.424; p < 0.05, r= -0.521).

Conclusion

The mRNA levels of elevated NfL in serum and CSF as well as lower EGFR and EGFR/NfL ratio in serum could help distinguish acute-phase MOGAD. Higher mRNA levels of NfL in serum and CSF of MOGAD patients help distinguish ADEM-like phenotype. In addition, serum EGFR/NfL mRNA ratio is indicative of disease severity in pediatric patients with MOGAD. Further investigations are warranted to elucidate the pathological mechanisms underlying these associations.
Transient heat stress protects from severe endothelial damage and dysfunction during prolonged experimental ex-vivo lung perfusion
Authors: Parapanov Roumen , Debonneville Anne , Allouche Manon , Lugrin Jérôme , Rodriguez-Caro Helena , Liaudet Lucas , Krueger Thorsten
Published: May 2024

Introduction

The pulmonary endothelium is the primary target of lung ischemia-reperfusion injury leading to primary graft dysfunction after lung transplantation. We hypothesized that treating damaged rat lungs by a transient heat stress during ex-vivo lung perfusion (EVLP) to elicit a pulmonary heat shock response could protect the endothelium from severe reperfusion injury.

Methods

Rat lungs damaged by 1h warm ischemia were reperfused on an EVLP platform for up to 6h at a constant temperature (T°) of 37°C (EVLP37°C group), or following a transient heat stress (HS) at 41.5°C from 1 to 1.5h of EVLP (EVLPHS group). A group of lungs exposed to 1h EVLP only (pre-heating conditions) was added as control (Baseline group). In a first protocol, we measured lung heat sock protein expression (HSP70, HSP27 and Hsc70) at selected time-points (n=5/group at each time). In a second protocol, we determined (n=5/group) lung weight gain (edema), pulmonary compliance, oxygenation capacity, pulmonary artery pressure (PAP) and vascular resistance (PVR), the expression of PECAM-1 (CD31) and phosphorylation status of Src-kinase and VE-cadherin in lung tissue, as well as the release in perfusate of cytokines (TNFα, IL-1β) and endothelial biomarkers (sPECAM, von Willebrand Factor -vWF-, sE-selectin and sICAM-1). Histological and immunofluorescent studies assessed perivascular edema and formation of 3-nitrotyrosine (a marker of peroxinitrite) in CD31 lung endothelium.

Results

HS induced an early (3h) and persisting expression of HSP70 and HSP27, without influencing Hsc70. Lungs from the EVLP37°C group developed massive edema, low compliance and oxygenation, elevated PAP and PVR, substantial release of TNFα, IL-1β, s-PECAM, vWF, E-selectin and s-ICAM, as well as significant Src-kinase activation, VE-cadherin phosphorylation, endothelial 3-NT formation and reduced CD31 expression. In marked contrast, all these alterations were either abrogated or significantly attenuated by HS treatment.

Conclusion

The therapeutic application of a transient heat stress during EVLP of damaged rat lungs reduces endothelial permeability, attenuates pulmonary vasoconstriction, prevents src-kinase activation and VE-cadherin phosphorylation, while reducing endothelial peroxinitrite generation and the release of cytokines and endothelial biomarkers. Collectively, these data demonstrate that therapeutic heat stress may represent a promising strategy to protect the lung endothelium from severe reperfusion injury.
Multifidelity topology design of a maritime survey operation with UUVs
Authors: Morey Danielle F. , Plate Randall S. , Wakayama Cherry Y. , Zabinsky Zelda B.
Published: May 2024

Advances in autonomous systems, maritime communications, and sensing technologies lead to increasing applications of unmanned underwater vehicles (UUVs). In this paper, we study a maritime survey operation topology design problem with UUVs that traverse an ocean environment and collect data from prespecified sensors or locations. This maritime scenario is analyzed via several models and simulation for the purpose of topology design for mission planning. We use a multifidelity approach to examine the trade-offs between different potential topology configurations of assigning UUVs to data collection sensors or locations. We develop three low-fidelity models that make simplifying assumptions. These models provide insight into the design characteristics and allow for sensitivity analysis with low computational cost. They are used to down-select potential configuration designs for further evaluation using a high-fidelity simulation model. A high-fidelity simulation model removes many simplifying assumptions and predicts how a topology design would perform under more realistic conditions. It gathers detailed performance metrics at the expense of higher computational cost. Our study uses this multifidelity approach to demonstrate key trade-offs for topology design. The optimal design of UUVs depends on mission-specific goals.