bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel lambdapapillomavirus in northern sea otters Enhydra lutris kenyoni, associated with oral hyperplastic nodules
Authors: Romero CH , Tuomi P , Burek-Huntington KA , Gill VA
Published: December 2023

A novel papillomavirus (PV) associated with hyperplastic nodules scattered over the muco-cutaneous border of the oral cavity of a dead, wild, subadult northern sea otter Enhydra lutris kenyoni (NSO) in 2004 in Homer, Alaska, USA, was genetically characterized. Primers for the amplification of 2 large overlapping DNA fragments that contained the complete genome of the NSO PV were designed. Sanger methodology generated sequences from which new specific primers were designed for the primer-walking approach. The NSO PV genome consists of 8085 nucleotides and contains an early region composed of E6, E7, E1, and E2 open reading frames (ORFs), an E4 ORF (contained within E2) lacking an in-frame proximal ATG start codon, an unusually long (907 nucleotide) stretch lacking any ORFs, a late region that contains the capsid genes L2 and L1, and a non-coding regulatory region (ncRR). This NSO PV has been tentatively named Enhydra lutris kenyoni PV2 (ElkPV2). Pairwise and multiple sequence alignments of the complete L1 ORF nucleotides and concatenated E1-E2-L1 amino acid sequences showed that the NSO PV is a novel PV, phylogenetically most closely related to southern sea otter PV1. The carboxy end of the E6 oncoprotein does not contain the PDZ-binding motif with a strong correlation with oncogenicity, suggesting a low-risk PV, which is in agreement with histopathological findings. However, the ElkPV2 E7 oncoprotein does contain the retinoblastoma (pRb) binding domain LXCXE (LQCYE in ElkPV2), associated with oncogenicity in some high-risk PVs. Further studies on the prevalence and clinical significance of ElkPV2 infections in NSO are needed.
Pengaruh Lingkungan Kerja dan Motivasi Kerja Terhadap Loyalitas Karyawan
Authors: Insani Auladina Nurul , Frianto Agus
Published: December 2023

Penelitiannini bertujuan untuk mengetahui pengaruh lingkungan kerja dan motivasi kerja terhadap loyalitas karyawan dipPT. Bunga Jaya Jati Bintang Mojokerto. Metode yang digunakan pada penelitian ini adalah metode penelitian kuantitatif dengan menggunakan pendekatan asosiatif. Jumlah sampel sebanyak 30 karyawan. Teknik pengumpulan data menggunakan kuesioner. Uji hipotesis menggunakan uji t, F dan R. Hasil penilitian ini menunjukkan bahwa (1) Lingkungan Kerja tidak berpengaruh terhadap Loyalitas Karyawan di PT. Bunga Jaya Jati Bintang Mojokerto dengan nilai thitung 1,042 < ttabel 1,703 dengan nilai signifikan 0,306 > 0.05. (2) Motivasi Kerja berpengaruh signifikan terhadap Loyalitas Karyawan di PT. Bunga Jaya Jati Bintang Mojokerto dengan nilai thitung 4,790 > ttabel 1,703 dengan nilai signifikan 0,00 < 0,05. (3) Lingkungan Kerja dan Motivasi Kerja berpengaruh secara simultan terhadap Loyalitas Karyawan di PT. Bunga Jaya Jati Bintang Mojokerto dengan nilai fhitung 44,518 > ftabel 3,35 dengan nilai signifikan sebesar 0,00 < 0,05.
Pengaruh Pelatihan Kerja dan Disiplin Kerja Terhadap Kinerja Karyawan CV. Tiga Agung Ngoro Jombang
Authors: Sari Inggar Purnama , Mahfudiyanto
Published: December 2023

Penelitian ini bertujuan untuk mengetahui pengaruh pelatihan kerja, disiplin kerja terhadap kinerja karyawan CV. Tiga Agung Ngoro Jombang. Metode yang digunakan pada penelitian ini adalah metode yang digunakan kuantitatif. Jumlah sampel sebanyak 100 karyawan. Teknik pengumpulan data menggunakan kuisioner. Teknik analisis data yang digunakan adalah regeresi linier berganda dengan alat bantu software komputer SPSS 25.0 .Uji hipotisis menggunakan uji t, uji f dan uji R. Hasil penelitian ini menunjukkan bahwa ( 1 ) pelatihan kerja secara parsial tidak ada pengaruh signifikan terhadap kinerja karyawan CV. Tiga Agung Ngoro Jombang dengan nilai t hutung kurang dari t table ( 2 ) disiplin kerja berpengaruh secara parsial terhadap kinerja CV. Tiga Agung Ngoro Jombang dengan nilai t hitung lebih besar daripada t tabel ( 3 ) pelatihan kerja dan disiplin kerja berpengaruh secara simultan terhadap kinerja karyawan CV.Tiga Agung Ngoro Jombang dengan nilai f hitung lebih besar dari f tabel
Pengaruh Beban Kerja dan Lingkungan Kerja Terhadap Kinerja Karyawan (Studi Kasus Pada Bagian Keperawatan Rumah Sakit Nahdlatul Ulama Jombang)
Authors: Sari Zhelika , Mahfudiyanto  , Laili Choirun Nisful
Published: December 2023

Penelitian ini bertujuan untuk mengetehui “pengaruh beban kerja dan lingkungan kerja terhadap kinerja karyawan Rumah Sakit Nahdlatul Ulama Jombang”. Penelitian ini menggunakan metode kuantitatif. Untuk kajian ini populasinya yaitu seluruh perawat RS Nahdlatul Ulama Jombang. Digunakannya sampel jenuh selaku teknik pengambilan sampelnya, dimana sampelnya berjumlah 60 karyawan. Teknik pengumpul data mempergunakan kuesioner yang telah dilakukan uji reliabilitas dan vaaliditasnya. Uji asumsi klasik mencakup uji normalitas, multikoloniearitas dan heteroskedastisitas, menggunakan analisis regresi linier berganda serta uji hipotesis (uji t dan F) serta  uji koefisien determinasi. Hasil penelitiannya untuk uji t (parsial) memperlihatkan bahwa variabel  beban kerja (X1) memengaruhi positif kinerja karyawannya (Y) serta variabel lingkungan kerja (X2) memengaruhi positif kinerja karyawannya (Y). Hasil penelitiannya untuk uji F (simultan) dihasilkan bahwa beban kerja (X1) dan lingkungan kerja (X2) memengaruhi signifikan kinerja karyawan (Y) secara simultan
Pengaruh Green Marketing Dan Brand Image Terhadap Keputusan Pembelian Deterjen Merek Rinso Pada Santri Putri PP. Roudlotul Qur’an Darul Falah 3
Authors: Laili Nur Zayyinatul , Aji Tony Seno , Irawati Winaika
Published: December 2023

Fokus penelitian ini adalah untuk melihat adanya pengaruh green marketing dan brand image terhadap keputusan pembelian deterjen merek Rinso pada santri putri PP. Roudlotul Qur’an Darul Falah 3. Penelitian ini merupakan penelitian kuantitatif. Responden adalah sejumlah 30 dipilih dengan simple random sampling. Kuesioner digunakan sebagai instrumen pengumpulan data. Data dianalisis dengan regresi linier berganda. Hipotesis diuji dengan uji t dan uji F. Penelitian ini menunjukkan bahwa baik secara parsial dan simultan green marketing dan brand image berpengaruh positif terhadap keputusan pembelian deterjen merek Rinso pada santri putri PP. Roudlotul Qur’an Darul Falah 3.
Analisis Efektivitas Break Even Point dan Margin of Safety pada PT. Sumber Mesthi Abadi
Authors: Imron Aqiel Khalisun Nada , Ardiana Meta
Published: December 2023

Perencanaan laba adalah rencana kerja yang telah dipertimbangkan dengan cermat dan dijelaskan secara real dalam bentuk angka dalam laporan keuangan untuk jangka pendek dan panjang. Perencanaan laba berguna untuk mengetahui seberapa banyak pengembalian modal yang akan diperoleh. Sehingga dalam memprediksi kinerja keuangan, perusahaan akan mempertimbangkan pendapatan dan beban-beban dalam produksi yang dihasilkan perusahaan. Penelitian ini bertujuan untuk mengetahui analisis efektivitas metode break even point dan margin of safety dalam perencanaan laba pada PT Sumber Mesthi Abadi Kabupaten Ngawi. Jenis penelitian ini merupakan penelitian kualitatif, sumber data yang digunakan adalah sumber data primer. Teknik pengumpulan data menggunakan metode dokumentasi, wawancara, dan observasi. Hasil dari penelitian menunjukkan bahwa analisis break even point dan margin of safety efektif digunakan perusahaan untuk perencanaan laba periode mendatang, dengan nilai break even point sejumlah Rp. 771.297.300 dan margin of safety sebesar 84%. Dengan menetapkan nilai break even point, perusahaan dapat mengetahui batas aman dalam kegiatan produksi
Analisis Kinerja Keuangan dalam Pengelolaan APBD Kabupaten Tuban di Masa Pandemi Covid-19
Authors: Mu’alimah Siti , Ervina Deasy
Published: December 2023

Pencapaian pembangunan suatu daerah adalah pengelolaan keuangan daerah, yang dapat diukur melalui kinerja keuangan daerah. Penelitian ini bertujuan untuk menganalisa kinerja keuangan pengelolaan APBD Kabupaten Tuban di masa pandemi Covid-19. Penelitian ini merupakan penelitian kualitatif deskriptif. Data yang diolah adalah Laporan Realisasi Anggaran tahun 2020 - 2021. Teknik pengumpulan data menggunakan teknik observasi, wawancara, dan dokumentasi. Teknik analisis menggunakan analisis kinerja keuangan pemerintah daerah. Hasil penelitian Analisis Varians Pendapatan Daerah menunjukkan kinerja Kabupaten Tuban dalam ketegori baik. Rasio Derajat Desentralisasi kemampuan Kabupaten Tuban. Rasio Kemandirian Keuangan Daerah tergolong rendah dengan pola hubungan Konsultatif. Rasio Ketergantungan Daerah sangat tinggi. Rasio Pertumbuhan Pendapatan Daerah positif. Rasio Efektivitas PAD sangat efektif. Analisis Varians Belanja Daerah menunjukkan kinerja Kabupaten Tuban dalam ketegori baik. Rasio Keserasian Belanja Daerah diprioritaskan untuk kebutuhan belanja operasi. Rasio Efisiensi Belanja Daerah menunjukkan efisien. Rasio Efisiensi Keuangan Daerah menunjukkan kurang efisien.
Pengaruh Kinerja Keuangan Terhadap Social Responsibility Perusahaan pada PT. Unilever Indonesia Tbk
Authors: Kurniawan Widiar Onny , Estiasih Soffia Pudji , Maharani Gintan Regita
Published: December 2023

This study has the aims of detecting the impact of ROA and ROE on CSR, the population of the financial statemenst of PT. Unilever Indonesia Tbk, sample of financial statements starting from 2018-2020 obtained 36 samples, the sampling mechanism is purposive sampling. As well as information collection techniques using documentation. Material testing using classical assumption test, multiple linear regression data analysis, hypothesis t test and F test. Based on simultaneous testing, the ROA impact on CSR is 0,000<0,05, ROE has an impact  on CSR 0,033<0,05. The implementation of better corporate social responbility can practice good things for the sustainability of the company in the long term. CSR disclosure can also show that a company is carring out its obligations properly according to existing regulations and the surrounding population and environment of the company. With the activities carried out by CSR, the company can give people confidence in the company’s products after which the good name of the company becomes excellent in the eyes of the population, and can grow financial capacity which can be shown from the ROA and ROE ratio.
Pengaruh Liabilitas dan Good Corporate Governance terhadap Tax Avoidance Perusahaan Food and Beverage pada Bursa Efek Indonesia Tahun 2017 – 2021
Authors: Parso Parso
Published: December 2023

This study aims to determine the effect of liabilities and good corporate governance (independent commissioners, audit committees, and institutional ownership) on tax avoidance in food and beverage companies listed on the IDX. The research conducted is quantitative research used to test hypotheses using statistical analysis tools regarding tax avoidance. Using secondary data by analyzing financial reports on food and beverage companies listed on the Indonesia Stock Exchange (IDX) for the period 2017 - 2021. Based on the data analysis conducted, it is found that liability has a positive and significant effect on tax avoidance, Independent Commissioner does not affect tax avoidance, Institutional Ownership has a negative and significant effect on tax avoidance, and the Audit Committee has no effect on tax avoidance in food and beverage companies listed on the Indonesia Stock Exchange for the period 2017 - 2021.

Abstrak  

Penelitian ini bertujuan untuk mengetahui pengaruh liabilitas dan good corporate governance yang terdiri dari variabel, komisaris independent, komite audit dan kepemilikan institusional terhadap tax avoidance pada perusahaan food and beverage yang terdaftar di BEI. Penelitian yang dilakukan adalah penelitian kuantitatif yang dipakai guna menguji hipotesis dengan menggunakan alat analisis statistik mengenai penghindaran pajak (tax avoidance). menggunakan data sekunder dengan cara menganalisis laporan keuangan pada perusahaan food and beverage yang terdaftar di Bursa Efek Indonesia (BEI) periode tahun 2017 – 2021. Berdasarkan analisis data yang dilakukan  didapatkan hasil bahwa Liabilitas berpengaruh positif dan signifikan terhadap tax avoidance, Komisaris Independen tidak berpengaruh terhadap tax avoidance, Kepemilikan Institusional berpengaruh negatif dan signifikan terhadap tax avoidance, dan Komite Audit tidak berpengaruh terhadap tax avoidance pada perusahaan food and beverage yang terdaftar di Bursa Efek Indonesia periode 2017 – 2021.

Kata Kunci: Liabilitas, Komisaris, Kepemilikan, Komite Audit, Penghindaran Pajak
LIFE: A metric for quantitively mapping the impact of land-cover change on global extinctions
Authors: Eyres Alison , Ball Thomas , Dales Michael , Swinfield Tom , Arnell Andy , Baisero Daniele , Durán América Paz , Green Jonathan , Madhavapeddy Anil , Balmford Andrew
Published: December 2023

Tracking and preventing continued extinctions requires robust spatially explicit metrics quantifying the impacts of human activities on habitat extent. Existing metrics either fail to consider species identity or focus solely on recent habitat losses. The persistence score approach represented an important development by combining species ecologies and land-cover data whilst considering the cumulative and non-linear impact of past habitat loss on species’ probability of persistence. However, it is computationally demanding, limiting its global use and application. Here we couple the persistence score approach with high-performance computing to generate global maps of what we term the LIFE (Land-cover change Impacts on Future Extinctions) metric for 29153 species of terrestrial vertebrates at 1 arc-minute resolution (3.4km2 at the equator). These maps quantify, for the first time, the marginal changes in the expected number of extinctions caused by (1) converting remaining natural vegetation to agriculture, and (2) restoring farmland to natural habitat. We demonstrate statistically that this approach integrates information on species richness, endemism, and past habitat loss. Our resulting maps can reliably be used at scales from 0.5-1000km2, and offer unprecedented opportunities to estimate the impact on extinctions of diverse actions, from dietary choices right through to global protected area development.
Person-Organization Fit and Employee Performance: Mediation Role Job Satisfaction and Organizational Commitment
Authors: Jufrizen Jufrizen , Khair Hazmanan , Annisa Nina , Hawariyuni Weni
Published: December 2023

Purpose – This study aimed to investigate and assess the effect of person-organization fit (POF) on employee performance (EP), with job satisfaction (JS) and organizational commitment (OC) acting as mediators.
Methodology – Questionnaires were used in this quantitative study, to obtain information from 61 employees, with subsequent analysis implementing the Structural Equation Model SmartPLS 4.0.
Results – The results showed that EP was significantly influenced by POF, JS, and OC. This indicated that POF relevantly influenced employee JS. POF and JS also significantly influenced OC. Moreover, the compatibility between employees and organization significantly influenced EP through JS and OC. POF also substantially influenced OC, mediated by JS. Based on the mediation by OC, JS then significantly influenced EP.
Originality – This study investigated the employee issues that significantly and widely impacted organizational performance. It also provided a deeper comprehension of the personal relationships between organization fit, employee engagement, and JS.
ÉTICA NO METAVERSO
Authors: De Assis Espinosa José Mauricio
Published: December 2023

Uma reflexão diante das novas perspectivas tecnológicas e suas implicações na sociedade atual, considerando as tendências sociais ante as redes, mundos virtuais, metaverso e inteligência artificial. Ponderando as questões éticas nestes ambientes e suas projeções sobre a vida real, de forma a se entrar em um dilema filosófico já observado desde a caverna de Platão, mas reeditado e atualizado hoje no conceito do metaverso e suas ações  efetivas na vida das pessoas. Avaliando a modernidade líquida, que ironicamente se solidifica como uma realidade ainda mais forte a cada dia, onde as pessoas vivem mais as vidas virtuais do que suas existências reais, criando uma atualização do paradigma do existir, do ser em seu conceito e a sua representação virtual, que de certa forma também é real, pois age de forma a executar ações palpáveis e com implicação real na vida de seus representantes humanos e vice versa.
EXPERIMENTOS DE PENSAMENTO COMO RECURSO METODOLÓGICO PARA UMA ONTOLOGIA E UMA EPISTEMOLOGIA
Authors: Melo dos Santos José Alfredo
Published: December 2023

O presente artigo tem por desígnio examinar os experimentos de pensamento, enquanto metodologia ontológica e/ou epistêmica. Considerando a taxonomia realizada por Rorbert Brown, acreditamos poder ser possível delinear a importância desse tipo de experimento. Essa classificação descreve dois tipos gerais de experimentos de pensamento, a saber: construtivos; e destrutivos. O primeiro remete a um intento de promover uma refutação de uma teoria. Já o segundo, vislumbra corroborar uma tese facilitando seu entendimento. Contudo, será observado as críticas realizadas a essa taxonomia. Ao estabelecer um entendimento das características gerais dos experimentos de pensamento, iremos verificar a sua aplicabilidade realizada por dois grandes nomes da abordagem da mente: a princípio, examinaremos o argumento do quarto chinês edificado por John Searle; em seguida, abordaremos a tese do mundo zumbi realizada por David Chalmers. Iremos também examinar a apologia configurada por Daniel Dennett que descreve os experimentos de pensamento como bombas de Intuições. Ao que tudo indica, o experimento de pensamento ocupa um papel fundamental na produção de conhecimento.
Flow Field Analysis of a Turbulent Channel Controlled by Scalloped Riblets
Authors: Yu Haidong , Huang Yi , Wang Yiqian , Qian Yuehong , Fu Song
Published: December 2023

Riblets are small protruding surfaces along the direction of the flow, and are one of the most well-known passive turbulent drag reduction methods. We investigated a scalloped riblet, the shape of which was constructed by smoothly connecting two third-order polynomials and was not as sharp in the tip as corresponding triangular riblets with the same height-width ratio. Numerical simulations were performed for turbulent channel flow with and without riblet control at an estimated optimum width of W+=20 and a height-width ratio of 0.5. A drag reduction rate of 5.77% was obtained, which is generally larger than the reported drag reduction rates of corresponding triangular riblets from the literature. Mean flow fields and second-order statistics of velocity, vorticity, and Liutex, a quantity introduced to represent vortices, were reported. It was found that streamwise vortices just above the riblet tips, which have a length scale of 200−300 in wall units, have an important influence on those statistics and thus the turbulence generation cycle and the drag reduction mechanism. Pre-multiplied energy spectra of streamwise velocity and the Liutex component were reported to reveal the length scales in the flow field. Instantaneous vortical flow fields visualized by the Liutex method were provided with emphases on the streamwise vortices just above riblet tips. It should be noted that the class of scalloped riblets is suitable for investigations on the influences of curvatures at the tip and the valley of the riblet in future.
Delayed lethal central nervous system toxicity induced by a low-dose intrathecal administration of bupivacaine: case report
Authors: Song Weishang , Zhang Hong , Li Xiaohui , Yu Chengxiang , Zhou Yuhong , Li Yuesu , Chen Bing
Published: December 2023

Spinal anesthesia by intrathecal administration of local anesthetic (LA) is a routine practice. Local anesthetic system toxicity, occurring in the central nervous system (CNS) and cardiovascular system, is a common and life-threatening adverse event of LA through a variety of routes, but is rarely encountered in spinal anesthesia when a very low dose of LA is injected into the subarachnoid space. Here, we report a case with manifestations of delayed lethal CNS toxicity after spinal anesthesia. A 55-year-old man underwent elective repair surgery for a chronic ulcer after receiving 10 mg intrathecal administration of bupivacaine. He developed nausea, agitation, paresthesia and myoclonus on the arms, legs, and trunk, as well as a gradually reduced level of consciousness one hour after intrathecal administration. He was sedated, intubated, and transferred to the intensive care unit. Both CT and MRI scans of the brain and assessments of blood showed no abnormalities. The electroencephalogram showed spike waves occurring at electrodes C3, C4, P3, P4, and T5. The patient was sedated continuously and treated with valproate. These symptoms were completely resolved in the following days without residual neurological complications. No cardiovascular complications were observed during the entire process. The delayed lethal symptoms in this case were most likely to be CNS toxicity induced by intrathecal bupivacaine administration. CNS toxicity after spinal anesthesia may be underestimated and unpredictable and should be vigilantly cared for in clinical settings.
Biochar as a tool for the improvement of soil and environment
Authors: Kabir Ehsanul , Kim Ki-Hyun , Kwon Eilhann E.
Published: December 2023

Biochar is a versatile and sustainable tool for agricultural and environmental remediation due to its unique physicochemical properties in terms of soil fertility, nutrient retention, and water holding capacity. As a stable carbon-rich material, biochar promotes plant growth and increases crop yields by enhancing microbial activity. It can also be used as a sorbent for removing pollutants such as heavy metals, organic contaminants, and nutrients from soil and water systems. However, the utility of biochar in soil and its ecological impact can be affected by the combined effects of many variables. This paper discusses the effects of biochar application on soil properties and its potential to mitigate various environmental challenges by enhancing soil composition, augmenting water accessibility, and removing pollutants as part of efforts to promote sustainable agriculture based on recent findings. These findings are expected to improve the utility of biochar in farming while contributing to the mitigation of climate change in diverse routes (e.g., by sequestering atmospheric carbon, improving soil quality, and reducing greenhouse gas emissions). This paper offers a promising opportunity to help harness the power of biochar and to pave the way for a more sustainable and resilient future.
Maternal consumption of a high-fat diet modulates the inflammatory response in their offspring, mediated by the M1 muscarinic receptor
Authors: Costa Suleyma Oliveira , Chaves Wenicios Ferreira , Lopes Priscilla Karla Fernandes , Silva Iracema M. , Burguer Beatriz , Ignácio-Souza Leticia M. , Torsoni Adriana Souza , Milanski Marciane , Rodrigues Hosana Gomes , Desai Mina , Ross Michael Glenn , Torsoni Marcio Alberto
Published: December 2023

Introduction

High-fat diet (HFD) consumption is associated with various metabolic disorders and diseases. Both pre-pregnancy and maternal obesity can have long-term consequences on offspring health. Furthermore, consuming an HFD in adulthood significantly increases the risk of obesity and metabolic disorders. However, an intriguing phenomenon known as the obesity paradox suggests that obesity may confer a protective effect on mortality outcomes in sepsis. In sepsis, activation of the cholinergic anti-inflammatory pathway (CAP) can help mitigate systemic inflammation. We employed a metabolic programming model to explore the relationship between maternal HFD consumption and offspring response to sepsis.

Methods

We fed female mice either a standard diet (SC) or an HFD during the pre-pregnancy, pregnancy, and lactation periods. Subsequently, we evaluated 28-day-old male offspring.

Results

Notably, we discovered that offspring from HFD-fed dams (HFD-O) exhibited a higher survival rate compared with offspring from SC-fed dams (SC-O). Importantly, inhibition of the m1 muscarinic acetylcholine receptor (m1mAChR), involved in the CAP, in the hypothalamus abolished this protection. The expression of m1mAChR in the hypothalamus was higher in HFD-O at different ages, peaking on day 28. Treatment with an m1mAChR agonist could modulate the inflammatory response in peripheral tissues. Specifically, CAP activation was greater in the liver of HFD-O following agonist treatment. Interestingly, lipopolysaccharide (LPS) challenge failed to induce a more inflammatory state in HFD-O, in contrast to SC-O, and agonist treatment had no additional effect. Analysis of spleen immune cells revealed a distinct phenotype in HFD-O, characterized by elevated levels of CD4+ lymphocytes rather than CD8+ lymphocytes. Moreover, basal Il17 messenger RNA (mRNA) levels were lower while Il22 mRNA levels were higher in HFD-O, and we observed the same pattern after LPS challenge.

Discussion

Further examination of myeloid cells isolated from bone marrow and allowed to differentiate showed that HFD-O macrophages displayed an anti-inflammatory phenotype. Additionally, treatment with the m1mAChR agonist contributed to reducing inflammatory marker levels in both groups. In summary, our findings demonstrate that HFD-O are protected against LPS-induced sepsis, and this protection is mediated by the central m1mAChR. Moreover, the inflammatory response in the liver, spleen, and bone marrow-differentiated macrophages is diminished. However, more extensive analysis is necessary to elucidate the specific mechanisms by which m1mAChR modulates the immune response during sepsis.
Case report: Hemophagocytic lymphohistiocytosis complicated by multiple organ dysfunction syndrome following aseptic encephalitis
Authors: Chen Quan-Ting , Chen Ming-Hua , Lin Yu-Kai , Yeh Ren-Hua , Lu Chun-Chi , Hsiao Po-Jen , Sung Yueh-Feng
Published: December 2023

Hemophagocytic lymphohistiocytosis (HLH) is a rare but potentially life-threatening condition caused by excessive immune activation. Secondary HLH is usually triggered by infection, most often from viral infection or malignancy. Here, we present a case of secondary HLH, complicated by multiple organ dysfunction syndrome triggered by critical aseptic encephalitis. A 27-year-old man without any underlying disease presented to our hospital with fever, disturbance of consciousness, and generalized seizures. The patient was diagnosed with aseptic encephalitis with super-refractory status epilepticus. Although antiseizure medications and immunoglobulins were administered, the patient developed multiple organ dysfunction syndrome. HLH was later diagnosed based on hypertriglyceridemia, hyperferritinemia, splenomegaly, cytopenia, and phagocytosis of nucleated cells, as shown by a blood smear of bone marrow aspiration. Treatment with pulse steroid therapy and plasmapheresis was initiated rather than chemotherapy because of the patient’s critical condition. However, the patient died of profound shock and multiple organ failure. Diagnosis of HLH is challenging in patients with severe infections because of similar clinical manifestations and laboratory findings. The early recognition of HLH provides patients with the opportunity to receive appropriate treatment, which can lead to increased survival and remission rates.
Pyruvate dehydrogenase kinase regulates macrophage polarization in metabolic and inflammatory diseases
Authors: Li Chenyu , Liu Chuanbin , Zhang Junfeng , Lu Yanyu , Jiang Bingtong , Xiong Huabao , Li Chunxia
Published: December 2023

Macrophages are highly heterogeneous and plastic, and have two main polarized phenotypes that are determined by their microenvironment, namely pro- and anti-inflammatory macrophages. Activation of pro-inflammatory macrophages is closely associated with metabolic reprogramming, especially that of aerobic glycolysis. Mitochondrial pyruvate dehydrogenase kinase (PDK) negatively regulates pyruvate dehydrogenase complex activity through reversible phosphorylation and further links glycolysis to the tricarboxylic acid cycle and ATP production. PDK is commonly associated with the metabolism and polarization of macrophages in metabolic and inflammatory diseases. This review examines the relationship between PDK and macrophage metabolism and discusses the mechanisms by which PDK regulates macrophage polarization, migration, and inflammatory cytokine secretion in metabolic and inflammatory diseases. Elucidating the relationships between the metabolism and polarization of macrophages under physiological and pathological conditions, as well as the regulatory pathways involved, may provide valuable insights into the etiology and treatment of macrophage-mediated inflammatory diseases.
Advances in the regulatory mechanisms of mTOR in necroptosis
Authors: Xie Yawen , Zhao Guoyu , Lei Xianli , Cui Na , Wang Hao
Published: December 2023

The mammalian target of rapamycin (mTOR), an evolutionarily highly conserved serine/threonine protein kinase, plays a prominent role in controlling gene expression, metabolism, and cell death. Programmed cell death (PCD) is indispensable for maintaining homeostasis by removing senescent, defective, or malignant cells. Necroptosis, a type of PCD, relies on the interplay between receptor-interacting serine-threonine kinases (RIPKs) and the membrane perforation by mixed lineage kinase domain-like protein (MLKL), which is distinguished from apoptosis. With the development of necroptosis-regulating mechanisms, the importance of mTOR in the complex network of intersecting signaling pathways that govern the process has become more evident. mTOR is directly responsible for the regulation of RIPKs. Autophagy is an indirect mechanism by which mTOR regulates the removal and interaction of RIPKs. Another necroptosis trigger is reactive oxygen species (ROS) produced by oxidative stress; mTOR regulates necroptosis by exploiting ROS. Considering the intricacy of the signal network, it is reasonable to assume that mTOR exerts a bifacial effect on necroptosis. However, additional research is necessary to elucidate the underlying mechanisms. In this review, we summarized the mechanisms underlying mTOR activation and necroptosis and highlighted the signaling pathway through which mTOR regulates necroptosis. The development of therapeutic targets for various diseases has been greatly advanced by the expanding knowledge of how mTOR regulates necroptosis.
Th1-related transcription factors and cytokines in systemic lupus erythematosus
Authors: Tang Yang-Yang , Wang Da-Cheng , Chen You-Yue , Xu Wang-Dong , Huang An-Fang
Published: December 2023

Systemic lupus erythematosus (SLE) is an inflammatory disorder related to immunity dysfunction. The Th1 cell family including Th1 cells, transcription factor T-bet, and related cytokines IFNγ, TNFα, IL-2, IL-18, TGF-β, and IL-12 have been widely discussed in autoimmunity, such as SLE. In this review, we will comprehensively discuss the expression profile of the Th1 cell family in both SLE patients and animal models and clarify how the family members are involved in lupus development. Interestingly, T-bet-related age-associated B cells (ABCs) and low-dose IL-2 treatment in lupus were emergently discussed as well. Collection of the evidence will better understand the roles of the Th1 cell family in lupus pathogenesis, especially targeting IL-2 in lupus.
Machine learning-based clinical decision support for infection risk prediction
Authors: Feng Ting , Noren David P. , Kulkarni Chaitanya , Mariani Sara , Zhao Claire , Ghosh Erina , Swearingen Dennis , Frassica Joseph , McFarlane Daniel , Conroy Bryan
Published: December 2023

Background

Healthcare-associated infection (HAI) remains a significant risk for hospitalized patients and a challenging burden for the healthcare system. This study presents a clinical decision support tool that can be used in clinical workflows to proactively engage secondary assessments of pre-symptomatic and at-risk infection patients, thereby enabling earlier diagnosis and treatment.

Methods

This study applies machine learning, specifically ensemble-based boosted decision trees, on large retrospective hospital datasets to develop an infection risk score that predicts infection before obvious symptoms present. We extracted a stratified machine learning dataset of 36,782 healthcare-associated infection patients. The model leveraged vital signs, laboratory measurements and demographics to predict HAI before clinical suspicion, defined as the order of a microbiology test or administration of antibiotics.

Results

Our best performing infection risk model achieves a cross-validated AUC of 0.88 at 1 h before clinical suspicion and maintains an AUC >0.85 for 48 h before suspicion by aggregating information across demographics and a set of 163 vital signs and laboratory measurements. A second model trained on a reduced feature space comprising demographics and the 36 most frequently measured vital signs and laboratory measurements can still achieve an AUC of 0.86 at 1 h before clinical suspicion. These results compare favorably against using temperature alone and clinical rules such as the quick sequential organ failure assessment (qSOFA) score. Along with the performance results, we also provide an analysis of model interpretability via feature importance rankings.

Conclusion

The predictive model aggregates information from multiple physiological parameters such as vital signs and laboratory measurements to provide a continuous risk score of infection that can be deployed in hospitals to provide advance warning of patient deterioration.
Desmosine as a biomarker for the emergent properties of pulmonary emphysema
Authors: Cantor Jerome
Published: December 2023

Developing an effective treatment for pulmonary emphysema will require a better understanding of the molecular changes responsible for distention and rupture of alveolar walls. A potentially useful approach to studying this process involves the concept of emergence in which interactions at different levels of scale induce a phase transition comprising a spontaneous reorganization of chemical and physical systems. Recent studies in our laboratory provide evidence of this phenomenon in pulmonary emphysema by relating the emergence of airspace enlargement to the release of elastin-specific desmosine and isodesmosine (DID) crosslinks from damaged elastic fibers. When the mean alveolar diameter exceeded 400 μm, the level of peptide-free DID in human lungs was greatly increased, reflecting rapid acceleration of elastin breakdown, alveolar wall rupture, and a phase transition to an active disease state that is less responsive to treatment. Based on this finding, it is hypothesized that free DID in urine and other body fluids may serve as a biomarker for early detection of airspace enlargement, thereby facilitating timely therapeutic intervention and reducing the risk of respiratory failure.
Effect of treatment with Lactococcus lactis NZ9000 on intestinal microbiota and mucosal immune responses against Clostridium perfringens in broiler chickens
Authors: Boodhoo Nitish , Shojadoost Bahram , Alizadeh Mohammadali , Astill Jake , Behboudi Shahriar , Sharif Shayan
Published: December 2023

Alterations in intestinal microbiota can modulate the developing avian intestinal immune system and, subsequently, may impact on resistance to enteric pathogens. The aim was to demonstrate that early life exposure to Lactococcus lactis, could affect either susceptibility or resistance of broilers to necrotic enteritis (NE). L. lactis NZ9000 (rL. lactis) pre-treatment at 1, 7, 14 and 21 days of age (DOA) led to a significant decrease in NE lesion scores in Clostridium perfringens infected chickens. C. perfringens Infection was associated with spatial and temporal decreases in mononuclear phagocytes and CD4+ αβ T cells. However, rL. Lactis pre-treatment and subsequent C. perfringens infection led to a significant increase in mononuclear phagocytes, CD8α + γδ T, αβ T cells (CD4+ and CD8α+) and B cells (IgM+, IgA+ and IgY+), as well as IL-12p40, IFN-γ and CD40. Differential expression of interleukin (IL)-6, IL-8, IL-10, IL-13, IL-18, IL-22, and transforming growth factor (TGF)-β were observed in L. lactis treated chickens when compared to C. perfringens infected chickens. Microbiota analysis in C. perfringens infected chickens demonstrated an increase in abundance of Bacillota, Bacteroidota, Pseudomonadota and Actinomycetota. These findings suggests that modulation of the chicken intestinal immune system by L. lactis confers partial protection 30 against NE.
Grazing exclusion alters soil methane flux and methanotrophic and methanogenic communities in alpine meadows on the Qinghai–Tibet Plateau
Authors: Wang Shilin , Chen Xindong , Li Wen , Gong Wenlong , Wang Zhengwen , Cao Wenxia
Published: December 2023

Grazing exclusion (GE) is an effective measure for restoring degraded grassland ecosystems. However, the effect of GE on methane (CH4) uptake and production remains unclear in dominant bacterial taxa, main metabolic pathways, and drivers of these pathways. This study aimed to determine CH4 flux in alpine meadow soil using the chamber method. The in situ composition of soil aerobic CH4-oxidizing bacteria (MOB) and CH4-producing archaea (MPA) as well as the relative abundance of their functional genes were analyzed in grazed and nongrazed (6 years) alpine meadows using metagenomic methods. The results revealed that CH4 fluxes in grazed and nongrazed plots were −34.10 and −22.82 μg‧m−2‧h−1, respectively. Overall, 23 and 10 species of Types I and II MOB were identified, respectively. Type II MOB comprised the dominant bacteria involved in CH4 uptake, with Methylocystis constituting the dominant taxa. With regard to MPA, 12 species were identified in grazed meadows and 3 in nongrazed meadows, with Methanobrevibacter constituting the dominant taxa. GE decreased the diversity of MPA but increased the relative abundance of dominated species Methanobrevibacter millerae from 1.47 to 4.69%. The proportions of type I MOB, type II MOB, and MPA that were considerably affected by vegetation and soil factors were 68.42, 21.05, and 10.53%, respectively. Furthermore, the structural equation models revealed that soil factors (available phosphorus, bulk density, and moisture) significantly affected CH4 flux more than vegetation factors (grass species number, grass aboveground biomass, grass root biomass, and litter biomass). CH4 flux was mainly regulated by serine and acetate pathways. The serine pathway was driven by soil factors (0.84, p < 0.001), whereas the acetate pathway was mainly driven by vegetation (−0.39, p < 0.05) and soil factors (0.25, p < 0.05). In conclusion, our findings revealed that alpine meadow soil is a CH4 sink. However, GE reduces the CH4 sink potential by altering vegetation structure and soil properties, especially soil physical properties.
Predictors of futile recanalization in basilar artery occlusion patients undergoing endovascular treatment: a post hoc analysis of the ATTENTION trial
Authors: Yi Tingyu , Li Kai , Lin Xiao-hui , Lin Ding-lai , Wu Yan-Min , Pan Zhi-nan , Zheng Xiu-fen , Chen Rong-cheng , Zeng Guoyong , Chen Wen-huo
Published: December 2023

Background

Few studies have focused on factors associated with futile recanalization in patients with an acute basilar artery occlusion (BAO) that was treated with modern endovascular therapy (EVT). The aim of this study was to explore the factors associated with futile recanalization in patients with an acute BAO presented within 12 h.

Methods

This is a post-hoc analysis of the ATTENTION trial (The Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion, ClinicalTrials.gov, number NCT 04751708). Demographics, clinical characteristics, acute stroke workflow interval times, and imaging characteristics were compared between the futile recanalization and favorable recanalization groups. The favorable outcome was defined as a modified Rankin scale (mRS) score of 0–3 at 90 days, successful reperfusion was defined as thrombolysis in cerebral infarction (TICI) 2b and 3 on the final angiogram, and futile recanalization was defined as failure to achieve a favorable outcome despite successful reperfusion. A multivariate analysis was performed to identify the predictors of futile recanalization.

Results

In total, 185 patients were included in the final analysis: 89 (48.1%) patients had futile recanalization and 96 (51.9%) patients had favorable recanalization. In the multivariable logistic regression analysis, older age (OR 1.04, 95% CI 1.01 to 1.08, p = 0.01) and diabetes mellitus (OR 3.35, 95% CI 1.40 to 8.01, p = 0.007) were independent predictors of futile recanalization.

Conclusion

Futile recanalization occurred in nearly half of patients with acute BAO following endovascular treatment. Old age and diabetes mellitus were identified as independent predictors of futile recanalization after endovascular therapy for acute BAO.
Overtaking collision avoidance for small autonomous uncrewed aircraft using geometric keep-out zones
Authors: Hawes Nathaniel C. , Wilhelm Jay P.
Published: December 2023

Autonomous uncrewed aircraft will require collision avoidance systems (CASs) designed with autonomy in mind as they integrate into the increasingly crowded national airspace system. Current uncrewed aircraft CASs typically require a remote pilot to execute avoidance or to provide poorly defined guidance that does not benefit autonomous systems. The Path Recovery Automated Collision Avoidance System (PRACAS) re-plans flight paths to autonomously adjust for collisions using path planners and keep-out zones (KOZs), but it does not currently detect or mitigate overtaking collisions. This work investigates the effect of geometric KOZs on overtaking scenarios for autonomous uncrewed aircraft. KOZ shapes were developed by relating relative velocities and turn rates of aircraft in overtaking scenarios and were tested using PRACAS. The operational ranges for approach heading, relative velocity, and look-ahead time were then determined. The set of KOZs that were developed prevented intruder aircraft from entering the minimum separation distance of one wingspan from the mission aircraft in overtaking scenarios with look-ahead times between 5 and 12 s, relative velocities of 2–20, and approach angles between 110° and −110° measured from the heading of the main UAS. Minimum separation was maintained for low-speed encounters with relative velocities between 1.1 and 2.0 for look-ahead times between 2 and 8 s for all approach angles. With look-ahead times ranging from 5 to 8 s, overtaking collisions of all tested approach angles and relative speeds are handled with more than twice the separation required for success, showing that the KOZs developed are feasible in possible autonomous CASs.
Chrysin-based supramolecular cyclodextrin-calixarene drug delivery system: a novel approach for attenuating cardiac fibrosis in chronic diabetes
Authors: Trotta Maria Consiglia , Herman Hildegard , Ciceu Alina , Mladin Bianca , Rosu Marcel , Lepre Caterina Claudia , Russo Marina , Bácskay Ildikó , Fenyvesi Ferenc , Marfella Raffaele , Hermenean Anca , Balta Cornel , D’Amico Michele
Published: December 2023

Introduction: Cardiac fibrosis is strongly induced by diabetic conditions. Both chrysin (CHR) and calixarene OTX008, a specific inhibitor of galectin 1 (Gal-1), seem able to reduce transforming growth factor beta (TGF-β)/SMAD pro-fibrotic pathways, but their use is limited to their low solubility. Therefore, we formulated a dual-action supramolecular system, combining CHR with sulfobutylated β-cyclodextrin (SBECD) and OTX008 (SBECD + OTX + CHR). Here we aimed to test the anti-fibrotic effects of SBECD + OTX + CHR in hyperglycemic H9c2 cardiomyocytes and in a mouse model of chronic diabetes.

Methods: H9c2 cardiomyocytes were exposed to normal (NG, 5.5 mM) or high glucose (HG, 33 mM) for 48 h, then treated with SBECD + OTX + CHR (containing OTX008 0.75–1.25–2.5 µM) or the single compounds for 6 days. TGF-β/SMAD pathways, Mitogen-Activated Protein Kinases (MAPKs) and Gal-1 levels were assayed by Enzyme-Linked Immunosorbent Assays (ELISAs) or Real-Time Quantitative Reverse Transcription Polymerase chain reaction (qRT-PCR). Adult CD1 male mice received a single intraperitoneal (i.p.) administration of streptozotocin (STZ) at a dosage of 102 mg/kg body weight. From the second week of diabetes, mice received 2 times/week the following i.p. treatments: OTX (5 mg/kg)-SBECD; OTX (5 mg/kg)-SBECD-CHR, SBECD-CHR, SBECD. After a 22-week period of diabetes, mice were euthanized and cardiac tissue used for tissue staining, ELISA, qRT-PCR aimed to analyse TGF-β/SMAD, extracellular matrix (ECM) components and Gal-1.

Results: In H9c2 cells exposed to HG, SBECD + OTX + CHR significantly ameliorated the damaged morphology and reduced TGF-β1, its receptors (TGFβR1 and TGFβR2), SMAD2/4, MAPKs and Gal-1. Accordingly, these markers were reduced also in cardiac tissue from chronic diabetes, in which an amelioration of cardiac remodeling and ECM was evident. In both settings, SBECD + OTX + CHR was the most effective treatment compared to the other ones.

Conclusion: The CHR-based supramolecular SBECD-calixarene drug delivery system, by enhancing the solubility and the bioavailability of both CHR and calixarene OTX008, and by combining their effects, showed a strong anti-fibrotic activity in rat cardiomyocytes and in cardiac tissue from mice with chronic diabetes. Also an improved cardiac tissue remodeling was evident. Therefore, new drug delivery system, which could be considered as a novel putative therapeutic strategy for the treatment of diabetes-induced cardiac fibrosis.
Whole-genome sequencing and comparative genome analysis of Xanthomonas fragariae YM2 causing angular leaf spot disease in strawberry
Authors: Qiu Yue , Wei Fangjun , Meng Han , Peng Menglin , Zhang Jinhao , He Yilu , Wei Lanfang , Ahmed Waqar , Ji Guanghai
Published: December 2023

Background

Angular leaf spot disease caused by plant pathogenic bacterium Xanthomonas fragariae seriously threatens strawberry crop production globally.

Methods

In this study, we sequenced the whole genome of X. fragariae YM2, isolated from Yunnan Province, China. In addition, we performed a comparative genome analysis of X. fragariae YM2 with two existing strains of X. fragariae YL19 and SHQP01 isolated from Liaoning and Shanghai, respectively.

Results

The results of Nanopore sequencing showed that X. fragariae YM2 comprises one single chromosome with a contig size of 4,263,697 bp, one plasmid contig size of 0.39 Mb, a GC content ratio of 62.27%, and 3,958 predicted coding genes. The genome of YM2 comprises gum, hrp, rpf, and xps gene clusters and lipopolysaccharide (LPS), which are typical virulence factors in Xanthomonas species. By performing a comparative genomic analysis between X. fragariae strains YM2, YL19, and SHQP01, we found that strain YM2 is similar to YL19 and SHQP01 regarding genome size and GC contents. However, there are minor differences in the composition of major virulence factors and homologous gene clusters. Furthermore, the results of collinearity analysis demonstrated that YM2 has lower similarity and longer evolutionary distance with YL19 and SHQP01, but YL19 is more closely related to SHQP01.

Conclusions

The availability of this high-quality genetic resource will serve as a basic tool for investigating the biology, molecular pathogenesis, and virulence of X. fragariae YM2. In addition, unraveling the potential vulnerabilities in its genetic makeup will aid in developing more effective disease suppression control measures.