bluuebunny/crossref_metadata_2025 huggingface dataset:
Uralic *tuppas – bridging Indic and Germanic
Authors: Pystynen Juho
Published: October 2024

Uralilainen *tuppas indoarjan ja germaanin silloittajanaSuomen tupas johdoksineen ja näiden vastineet pohjoisessa itämerensuomessa voidaan parhaiten johtaa useimpien suomen murteiden sekä vepsän osoittamasta kantasuomen asusta *tup̆pas. Muutamat sanansisäiseen yksittäisklusiiliin viittaavat vastineet kuten karjalan tuvas katson selittyvän ryväs-sanueen sekundääriseksi vaikutukseksi. Tunkelon (1918) germaaninen lainaetymologia ← kantagermaanin *þūƀaz ’mätäs, pensas’ ei tämän valossa ole puolustettavissa. Koivulehdon (1999) rinnastus toiseen kantagermaanin sanueeseen *tuppaz ’tupsu, tukko, yläpää’ näyttää paremmalta, mutta tältä sanueelta taas puuttuu oma indoeurooppalainen etymologia. Kyseessä onkin pikemmin laina itämerensuomesta luoteisgermaaniin, sillä itämerensuomen sanueelle voidaan löytää vastineita myös idempää, marista: deminutiivijohdos *tŭpka ’tuppo, tukka’, ja komista: aines tup- useissa johdoksissa kuten tupji̮- ’tukkia’, tupi̮rt- ’kääriä’, ja yhdyssanoissa kuten tup-jura ’tupsupää’. Poikkeusedustus *u > komin u lienee säännöllinen *p:n edellä. Sanueen *-as-vartalo itämerensuomessa silti viittaa indoeurooppalaiseen laina-alkuperään, ja myös uusi laina­etymologia voidaan esittää: kyse on vanhasta indoiranilaisesta (arjalaisesta) lainasta, jota parhaiten vastaa muinaisindoarjan stū́pa- ’mätäs, tupas, päälaki, ym.’ < kantaindoiranin *stúHpas. Samaan etymologiseen pesueeseen voitaisiin jatko-oletuksin liittää vielä marin *tŭp ’selkä’ (mikäli aiemmin ’yläselkä’) ja suomen tukka (arjalaisen sanueen jostain toisesta variantista, vrt. muinais­indoarjan stúkā- ’tupsu, tukko’). Huomattavinta kuitenkin on, että germaanin *tuppaz-sanue ei sovi indoiranin sanojen perintövastineeksi, ja näiden yhteyden mahdollistaa ainoastaan itämerensuomen kautta välittyminen – samaan tapaan kuin esim. jo ennestään tunnettu repo-sanueen lainautuminen indoiranista itämerensuomen kautta pohjoisgermaaniin. Vastaavaa takaisinlainautumisen mahdollisuutta onkin syytä pitää silmällä myös jatkossa tarkasteltaessa itämerensuomalaisten tai yleisemmin uralilaisten kielten sanueita, joille on esitetty useampia lainaetymologioita.
Ein Fall für zwei (oder drei) – Liquid metathesis substitution in Germanic loanwords in Finnic: old and new cases
Authors: Metsäranta Niklas
Published: October 2024

Itämerensuomen germaanilainojen likvidametateesisubstituutiosta: uusia ja vanhoja tapauksiaTässä artikkelissa käsittelen itämerensuomen vanhoissa germaanilainoissa tavattavaa niin kutsuttua likvidametateesia, jossa sananalkuisen konsonanttiyhtymän jälkiosana oleva likvida heittyy sanansisäiseen asemaan. Alkuun artikkelissa tarkastelen lyhyesti entuudestaankin tunnettuja likvidametateesitapauksia, pääasiallisena mielenkiinnon kohteenani on kuitenkin selvittää, voidaanko kantasuomeen rekonstruoitavat sanat, ksm. *kiiltä-, *purka-, *tarkka, *tarpo-, *turkka- ja *turta, selittää likvidametateesin avulla germaanisiksi lainasanoiksi. Johtopäätökseni artikkelissa on, että mainitut sanat ovat viime kädessä lainautuneet kantagermaaniin rekonstruoiduista sanoista *glītan- ’to shine, sparkle’, *bruk(k)ōn- ’to break, crumble’, *straka- ’stretched’, *þrappōn-/*þrabōn ’to trot’, *struk(k)ōn- ’to stroke’ ja *þrutan ’lack, want; weariness’. Lopuksi pohdin muutamia mahdollisia lisäesimerkkejä ja lainojen ikäämistä. Artikkelini osoittaa, että niinkin tarkkaan tutkitusta aiheesta kuin itämerensuomen germaaniset lainasanat voidaan vielä tehdä uusia etymologisesti varteenotettavia huomioita.
A Germanic etymology for Saami liiki ‘(human) skin’
Authors: Kuokkala Juha
Published: October 2024

Germaaninen etymologia saamen liiki ’iho’ -sanalleYleissaamelainen ’ihoa’ merkitsevä sana, pohjoissaamen liiki, koltansaamen le'šǩǩ ym. on toistaiseksi ollut vailla vakuuttavaa etymologiaa; esitetty (laina)rinnastus itämerensuomen liha-sanaan on varsinkin äänteellisesti ongelmallinen. Artikkelissa esitetään uutena selityksenä sanan olevan germaaninen laina, lähinnä kantaskandinaavin sanasta *līka > muinaisskandinaavin lík ’hahmo, keho, ruumis’. Itäsaamen sanoissa esiintyvä -šk-yhtymä selittyy saamen muinaismurteiden välisessä lainautumisessa tapahtuneella etymologisella nativisaatiolla.
The palaeo-Baltic substrate: a methodological exploration
Authors: Jakob Anthony
Published: October 2024

Substraattisanasto Itämeren alueen kielissä: huomioita tutkimus­metodeistaUseat tutkijat, tunnetuimpana Paul Ariste, ovat esittäneet, että indoeurooppalaisten kielten ohella myös alkuperältään tuntemattomat kielet ovat vaikuttaneet itämerensuomen sanastoon. Ehdotus on kuitenkin saanut suhteellisen vähän huomiota eikä sen selvittelemiseen ole yleisesti hyväksyttyjä kielitieteellisiä menetelmiä. Tässä artikkelissa tarkastelen erilaisia metodologisia lähestymistapoja yhdistelemällä kielihistoriallista tietoa itämerensuomalaisista ja balttilaisista kielistä. Johtopäätöksenä totean, että monet aiemmat ehdotukset perustuvat pelkkään semantiikkaan ja alkuperänselityksen puuttumiseen, mikä ei riitä perustelemaan substraattialkuperää. Epäuralilainen fonotaksi tai morfologia eivät nekään voi todistaa nimenomaan ei-indoeurooppalaisesta substraatista. Vahvana voimme pitää alkuperäväitettä vain, jos sen tueksi löytyy vähintään kaksi toisistaan riippumatonta leksikaalista todistetta ja jos keskinäinen lainautuminen tai yhteinen perimä voidaan sulkea pois. Emme voi osoittaa kantasuomen sanaa *sīka ’siika’ lainaksi jostakin substraattikielestä, koska todisteeksi ei ole löydettävissä ainuttakaan minkään muun kielen sanaa, joka ei voisi palautua lainaan itämerensuomesta. Toisaalta kantasuomen *silakka, preussin sylecke ja muinaisskandinaavin síld ’silakka’ näyttävät hyviltä ehdokkailta rinnakkaisiksi substraattilainoiksi. Muita artikkelissa käsiteltyjä mahdollisia substraattilainoja ovat kulkusanoilta vaikuttavat ’tuhatta’ merkitsevät kantasuomen *tuhante̮-, kantamordvan *t́ožəm-, kantabaltin *tū’stant- jne., joitten äännesuhteet ovat ongelmallisia niin indoeurooppalaisten kuin uralilaistenkin kielihaarojen välillä, sekä ’sammalta’ merkitsevät kantabaltin *samanā-, kantasuomen *sammal, pohjoissaamen seamul jne., jolla saamessa on useita hankalasti yhteen sovitettavia variantteja, mikä viittaisi lähtömuotoon muinaislapissa, Aikion ehdottamassa substraattikielessä. Tämän aineiston perusteella pidän epätodennäköisenä, että koko käsitellyn sanaston takana olisi yksi ainoa monoliittinen lähtökieli. Luultavasti Itämeren alueen kielet ovat saaneet substraattisanastoa useista, mahdollisesti eri kielikuntiin kuuluneista kielistä.
Lounaisitämerensuomalaiset denominaalit johtimet *-As (: *-AhA-), *-k̆As ja *-k̆kAs
Authors: O’Rourke Patrick
Published: October 2024

Southwest Finnic denominal derivative suffixes *-As (: *-AhA-), *-k̆As and *-k̆kAsIn this article, I examine Southwest Finnic variants of the derivative suffixes *-As (: *-AhA-), *-k̆As and *-k̆kAs. The suffixes themselves are common in Finnic, but the distribution of certain words formed with the suffixes gives reason to assume a local development of the use of the suffixes. Southwest Finnic linguistic forms mentioned in the article are Courland and Salaca Livonian, and the insular and western dialects of North Estonian. The suffix *-As (: *-AhA-) has spread analogically in the Livonian lexicon and the function of the suffix in Livonian to some extent resembles that of the Latvian nominative singular suffix. The suffix *-k̆As is secondary, deriving from the merger of *-k̆A and *-As. The suffix *-k̆kAs is also secondary and derives in Southwest Finnic from the merger of the suffixes *-kkA and *-As. In total, 19 word stems with the suffixes *-As, *-k̆As and *-k̆kAs have a Southwest Finnic distribution, evidencing the innovative addition of the suffixes.
Impact of zero-sequence mutual inductance on underreach distance
protection and an adaptive solution
Authors: Zhang Hong Xi , Xu Hai Yang , Xu Xiao Chun , Zhao Qing Chun
Published: October 2024

Based on a real project, the performance of the pilot distance
protection under a cross-country grounding fault on the parallelline is
analysed. The zero-sequence mutual inductance is the root cause for failure
operation of the pilot distance protection. The analysis shows that
shrinking the zero-sequence compensation coefficient or reach setting of
grounding distance protection can effectively prevent the overreach issue,
but it cannot meet the sensitivity of the underreach distance protection,
and there is a risk of failure operation under some extreme situations. In
order to solve the problem, the impact of the zero sequence mutual
inductance is studied to find out whether the additional impedance can
result in an underreach or overreach problem. At the same time, the
characteristics are analysed when the cross-country grounding fault occurs
on the parallel lines. After the analysis, an adaptive zero-sequence mutual
compensation method is proposed. The new method can enable compensation
adaptively based on the zero-sequence current direction and the phase
current direction. The performance of the pilot distance protection is
calculated using the new method, and the pilot distance protection can
operate correctly, which verifies that the method is valid.
FRANCOPHONE RESEARCH WORKS ON HRYHORII SKOVORODA (1820s — 2010s)
Authors: Kravets Yarema
Published: October 2024

The paper presents significant facts concerning the French-language interpretation of the writings by Hryhorii Skovoroda (1722—1794). Having begun as far back as the 1820s, 34 years following the philosopher’s death, Francophone presentations of Skovoroda’s works and ideas offered interesting reflections on the extraordinary talent of the Ukrainian philosopher. The desire of both French and Ukrainian literary scholars of the French diaspora to familiarize the wider public with Skovoroda's legacy resulted in numerous publications in Francophone editions from the 1920s—1930s and the second half of the 19th century.
The paper also takes into account anthology-type Francophone editions of Ukrainian literature that present individual samples of Hryhorii Skovoroda’s works. Additionally, it examines the 1973 Paris Skovoroda Colloquium, including interpretations focusing on Platonic elements in the Ukrainian philosopher’s works, particularly his ideas of self-cognition and pre-personalism.
Many works emphasized that H. Skovoroda was a typical impersonation of Ukrainian mentality and spirituality, serving as an archetype of the Ukrainian people in terms of their deepest psychological roots. He was interpreted as a philosopher who was a spokesman for his people. Valuable multifaceted research works on H. Skovoroda’s legacy emerged in the 1920s, during the period of the “Ukrainian National Revival,” when Skovoroda’s main point, that is Socratic desire “to know oneself,” proved to be particularly relevant. French-language  research works on the legacy of Skovoroda arose interest to the Ukrainian philosophy in general.
Work-Related Stress and Uncertainty Amid Change: Can Workplace Coaching Make a Difference?
Authors: Ebrahimi Mehdi
Published: October 2024

Work-related stress, job insecurity and uncertain carer future are each detrimental to employee performance, productivity, behaviour, job satisfaction, and wellbeing. The literature provides evidence suggesting a relationship between organisational change and work-related stress. Whilst most existing research focus on positive aspects or negative consequences of change and restructure, this article goes further seeking to understand whether or not workplace coaching is perceived as helpful to reduce work-related stress in the face of change and uncertainty. Data were initially collected, as part of a larger study, in three sequential phases from Australian rail organisations. The results relevant to the current article are a subset of results from the larger study. Results had previously suggested that workplace coaching contributed towards positive behavioural shifts and increased employee motivation in the face of change. Results had also suggested that certain elements in a coaching relationship, including confidentiality and trust, were critical for the effectiveness of internal coaching. A subset of quantitative results reported in this paper provided further evidence suggesting that workplace coaching, possibly both internal and external forms of it, can potentially contribute to reduce work-related stress in the face of change and restructure.
Factors Affecting the Career Choice of Intern Physicians and Their Perspectives on Family Medicine Residency
Authors: Demirbas Nur , Kucukceran Hatice , Karaoglu Nazan , Cihan Fatma Goksin
Published: October 2024

Aim: This study aimed to determine the career preferences of intern physicians, the factors affecting these preferences and their perspectives on family medicine residency.

Method: In this descriptive study, final-year students at a medical school were asked to complete a questionnaire about their socio-demographic information, factors influencing their career choice, and their views on the discipline of family medicine.

Results: The study involved 220 students with a mean age of 24.35±1.06 years (range: 23-29), of whom 63.2% (n=139) were female. The three most popular career choices were Dermatology (22.7%), Family Medicine (22.3%), and Psychiatry (17.3%). Among the interns, 87.3% (n=192) thought that family medicine was not sufficiently valued by society and 76.4% (n=168) by other specialists. The factors affecting the preference for family medicine specialty were determined as the ability to adjust working hours, less physical fatigue, less stress, establishing long-term relationships with patients, and providing work-life balance. Of the interns surveyed, 74.6% (n=164) believed that family physicians could provide most of the health services needed by patients but that they did too much simple and repetitive work (63.6%).

Conclusion: It is seen that the specialty of family medicine ranked in the top three in career choice among the interns of this medical faculty. It is also important to note that the majority of the interns stated that family physicians were engaged in simple and repetitive tasks and had limited career opportunities when they could provide most of the health services.

Keywords: career choice, family practice, medical students, residency
Seven continents. One sky
Authors: Vuţoiu Beatrice Georgiana , Tǎbǎcaru Maria Bianca , Beşchea George Andrei , Câmpean Ştefan Ioan , Bulmez Alexandru Mihai , Nǎstase Gabriel
Published: October 2024

This paper explores the global impacts of climate change and pollution across diverse regions, highlighting unique challenges and innovative initiatives. From rising temperatures and severe droughts in Africa and Australia to melting glaciers in the Arctic and pollution in Asia, each continent faces significant environmental threats. Despite these challenges, countries are making strides in renewable energy, conservation, and community-based actions. International agreements and local indigenous practices play vital roles in these efforts. The paper concludes with a call for continued global cooperation and local action, emphasizing the potential for a sustainable future through collective innovation and resilience-building. Through this comprehensive analysis, the paper underscores the urgency and possibility of addressing global warming and pollution for a healthier planet.
A survivability analysis of enterprise hard drives incorporating the impact of workload
Authors: Mallik Aman , Reddy B Ranjith , Sahoo Gadadhar
Published: October 2024

Introduction

Hard disk drive (HDD) failure is a significant cause of downtime in enterprise storage systems. Research suggests that data access rates strongly influence the survival probability of HDDs.

Methods

This paper proposes a model to estimate the probability of HDD failure, using factors such as the total data (TD) read or written and the average access rate (AAR) for a specific drive model. The study utilizes a dataset of HDD failures to analyze the effects of these variables.

Results

The model was validated using case studies, demonstrating a strong correlation between access rate management and reduced HDD failure risk. The results indicate that managing data access rates through improved throttle commands can significantly enhance drive reliability.

Discussion

Our approach suggests that optimizing throttle commands at the storage controller level can help mitigate the risk of HDD failure by controlling data access rates, thereby improving system longevity and reducing downtime in enterprise storage systems.
Exploring quantitative trait nucleotides associated with response to yam mosaic virus severity and tuber yield traits in Dioscorea praehensilis Benth. germplasm via genome-wide association scanning
Authors: Adewumi Adeyinka S. , Adejumobi Idris I. , Opoku Vincent A. , Asare Paul A. , Adu Michael O. , Taah Kingsley J. , Stanley Adekemi E. , Olatunde Temitope E. , Afutu Emmanuel , Akaba Selorm , Mushoriwa Hapson , Agre Paterne A.
Published: October 2024

Background

Yam production in sub-Saharan African countries faces challenges due to susceptibility to yam mosaic virus (YMV) disease, leading to significant yield losses. Dioscorea praehensilis, a semi-cultivated yam species known for its high yield and resistance to YMV, can be utilized as a new variety and a gene source to enhance tuber yield and YMV resistance of White Guinea yam. Investigating the genetic basis of tuber yield-related traits and YMV resistance in D. praehensilis through association mapping will facilitate the traits discovery and deployment into the yam breeding program.

Methodology

A total of 132 D. praehensilis genotypes were evaluated in 2022 and 2023 seasons for tuber yield per plant, tuber size ratio and for mosaic virus severity response. The genotypes were sequenced using SNP markers generated from Diversity Array Technology Platform. The trait association analysis was conducted using mixed linear model implemented in GWASpoly package followed for putative genes analysis.

Results

Population structure and phylogeny analyses using 4,525 single nucleotide polymorphism (SNP) markers grouped the 132 D. praehensilis genotypes into three clusters. Using multiple gene action models which include dominant, additive, and general models, 27 SNP markers were significantly identified to be associated with the tuber yield, tuber size ratio and yam mosaic virus severity. Of these 27 SNPs, we identified three and two SNP markers for tuber yield and yam mosaic virus severity, respectively as stable markers across years. Using gene annotation, we identified 10 putative genes such as Serine/threonine-/dual specificity protein kinase, catalytic domain involved in starch biosynthesis and Ribosomal protein L5 involved in defense signaling against virus diseases. The marker effect revealed that alleles CC and TT were associated with high tuber yield, while AA and AC were linked with low tuber yield. For YMV severity response, alleles CC and CT were linked with low YMV severity, while TT was associated high YMV severity prediction.

Conclusion

The results of this study offer valuable insights into comprehending the functional networks involved in developing strategies to enhance tuber yield and resistance to yam mosaic virus in Dioscorea spp. The markers and candidate genes discovered in this research will serve as crucial genomic resources for selection of D. praehensilis and other yam species.
SNAP25-induced MYC upregulation promotes high-grade neuroendocrine lung carcinoma progression
Authors: Chen Zhiqiang , Wang Shujing , Wang Jingrui , Wang Ying , Qi Xiangjun , An Bo , Sun Lingling , Lin Lizhu
Published: October 2024

Background

This study investigated the expression and role of Synaptosome associated protein 25 (SNAP25) in high-grade neuroendocrine carcinoma (HGNEC).

Methods

We used differentially expressed analysis and weighted gene co-expression network analysis (WGCNA) to identify key genes and modules in HGNEC. KEGG and GO analyses helped understand these genes’ roles, and ROC curves assessed their diagnostic value. We also studied SNAP25’s relation to immune infiltration and confirmed findings with in vitro and vivo experiments and datasets.

Results

WGCNA identified 595 key genes related to pathways like MAPK signaling, GABAergic synapse, and cancer-related transcriptional misregulation. Top genes included SNAP25, MYC, NRXN1, GAD2, and SYT1. SNAP25 was notably associated with M2 macrophage infiltration. Dataset GSE40275 confirmed SNAP25’s high expression and poor prognosis in HGNEC. qRT-PCR and WB analyses showed increased SNAP25 and c-MYC levels in HGNEC, promoting MEK/ERK pathway activity. Reducing SNAP25 decreased H1299 cell proliferation, migration, invasion, and levels of c-MYC, MEK, and ERK. Finally, in vivo experiments further confirmed that SNAP25 knockout can inhibit tumor growth.

Conclusion

SNAP25 regulates c-MYC activation by stimulating the MEK/ERK pathway, ultimately influencing the development of HGNEC.
Risk factors for type 2 diabetes mellitus in Chinese rheumatoid arthritis patients from 2018 to 2022: a real-world, single-center, retrospective study
Authors: Pei Ruomeng , Wang Jia , He Peifeng , Yu Qi , Zhang Shengxiao , Shi Gaoxiang , Liu Geliang , Li Xiaofeng
Published: October 2024

Introduction

In patients with rheumatoid arthritis (RA), the increased risk of concomitant type 2 diabetes mellitus (T2D) is an important contributor to increased mortality and decreased quality of life; however, the mechanisms and pathogenetic factors remain unknown.

Methods

In this study, we aimed to assess the risk factors for T2D in patients with RA. We recruited 206 healthy controls and 488 patients with RA, 160 of whom had comorbid T2D. General clinical information, disease characteristics, and circulating lymphocyte levels detected using modified flow cytometry were collected from all participants. Logistic regression models adjusted for confounders were fitted to estimate the risk factors of T2D in patients with RA.

Results

The incidence of RA in patients with T2D was 15.6%. Patients with RA and T2D had a longer disease duration, higher BMI, and a higher incidence of hypertension and a family history of diabetes than those with RA but no T2D. The absolute numbers of T helper 2 cell (Th2) and Regulatory T cells (Treg) decreased in patients with RA and T2D, which led to an increase in the ratios of Th1/Th2 and Th17/Treg cells. Multivariate logistic regression analysis showed that a family history of diabetes, a higher incidence of hypertension, higher neutrophil-lymphocyte ratio (NLR) levels, lower platelet-lymphocyte ratio (PLR) levels, and fewer circulating Th2 and Treg cells were associated with an increased risk of T2D in patients with RA.

Discussion

The levels of peripheral lymphocytes, especially Th2 and Treg cells, are closely related to the occurrence of T2D in patients with RA; however, the influence of body mass index (BMI), family history of diabetes, and systemic inflammation should not be ignored.
Case report: Rare Guillain-Barré syndrome variants and mild encephalitis/encephalopathy with a reversible splenial lesion as the para-infectious manifestations of SARS-CoV-2 infection
Authors: Si Wei , Li Yuanrui , Du Ganqin
Published: October 2024

Background

The Coronavirus disease 19 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a threat to human health. Although the COVID-19 pandemic is finished, some peoples are still suffering from this disease. Herein, we report the first case of SARS-CoV-2-associated Guillain-Barré syndrome (GBS) presenting as polyneuritis cranialis (PNC) and acute panautonomic neuropathy (APN) variants, accompanied by mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) and hyponatremia.

Case presentation

A 32-year-old female patient with symptoms indicating multiple cranial nerve involvement, as well as sympathetic and parasympathetic nervous system dysfunction, was diagnosed as SARS-CoV-2-associated GBS presenting as PNC and APN variants, accompanied by MERS and hyponatremia. Following treatment with immunoglobulin, methylprednisolone, and symptomatic care, the patient’s inflammatory cytokines and serum sodium became normal. However, some residual symptoms such as postural hypotension, fatigue, and mild dysarthria persisted at the 9-month follow-up.

Conclusion

This case highlights the unique presentation of SARS-CoV-2 infection. The involvement of both the central nervous system (CNS) and the peripheral nervous system (PNS) in this case underscores the complex neurological manifestations of COVID-19. Although the exact underlying pathogenesis of this case is unclear, inflammatory cytokines, particularly IL-6, may be implicated. Further research is needed to better understand the mechanisms underlying these complications and to optimize treatment strategies for affected patients.
Identification of key biomarkers and therapeutic targets in sepsis through coagulation-related gene expression and immune pathway analysis
Authors: Ge Jing , Deng Qijie , Zhou Rui , Hu Yahui , Zhang Xiaotong , Zheng Zemao
Published: October 2024

Sepsis, characterized by a widespread and dysregulated immune response to infection leading to organ dysfunction, presents significant challenges in diagnosis and treatment. In this study, we investigated 203 coagulation-related genes in sepsis patients to explore their roles in the disease. Through differential gene expression analysis, we identified 20 genes with altered expression patterns. Subsequent correlation analysis, visualized through circos plots and heatmaps, revealed significant relationships among these genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that these genes are involved in immune response activation, coagulation, and immune receptor activity. Disease Ontology (DO) enrichment analysis further linked these genes to autoimmune hemolytic anemia and tumor-related signaling pathways. Additionally, the CIBERSORT analysis highlighted differences in immune cell composition in sepsis patients, revealing an increase in neutrophils and monocytes and a decrease in inactive NK cells, CD8 T cells, and B cells. We employed machine learning techniques, including random forest and SVM, to construct a diagnostic model, identifying FCER1G and FYN as key biomarkers. These biomarkers were validated through their expression levels and ROC curve analysis in an independent validation cohort, demonstrating strong diagnostic potential. Single-cell analysis from the GSE167363 dataset further confirmed the distinct expression profiles of these genes across various cell types, with FCER1G predominantly expressed in monocytes, NK cells, and platelets, and FYN in CD4+ T cells and NK cells. Enrichment analysis via GSEA and ssGSEA revealed that these genes are involved in critical pathways, including intestinal immune networks, fatty acid synthesis, and antigen processing. In conclusion, our comprehensive analysis identifies FCER1G and FYN as promising biomarkers for sepsis, providing valuable insights into the molecular mechanisms of this complex condition. These findings offer new avenues for the development of targeted diagnostic and therapeutic strategies in sepsis management.
TEAD transcription factor family emerges as a promising therapeutic target for oral squamous cell carcinoma
Authors: Wang Shuang , Shao Dan , Gao Xiaoyan , Zhao Peng , Kong Fanzhi , Deng Jiawei , Yang Lianzhu , Shang Wei , Sun Yaping , Fu Zhiguang
Published: October 2024

The treatment of oral squamous cell carcinoma (OSCC) remains a significant difficulty, as there has been no improvement in survival rates over the past fifty years. Hence, exploration and confirmation of new dependable treatment targets and biomarkers is imperative for OSCC therapy. TEAD transcription factors are crucial for integrating and coordinating multiple signaling pathways that are essential for embryonic development, organ formation, and tissue homeostasis. In addition, by attaching to coactivators, TEAD modifies the expression of genes such as Cyr61, Myc, and connective tissue growth factor, hence facilitating tumor progression. Therefore, TEAD is regarded as an effective predictive biomarker due to its significant connection with clinical parameters in several malignant tumors, including OSCC. The efficacy of existing drugs that specifically target TEAD has demonstrated encouraging outcomes, indicating its potential as an optimal target for OSCC treatment. This review provides an overview of current targeted therapy strategies for OSCC by highlighting the transcription mechanism and involvement of TEAD in oncogenic signaling pathways. Finally, the feasibility of utilizing TEAD as an innovative approach to address OSCC and its potential clinical applications were analyzed and discussed.
Mineralogy and geochemistry of the Cambrain Shuijingtuo Formation black shales from Western Hubei, China: implications on enrichment of critical metals and paleoenvironment
Authors: Wang Yuan , Li Jing , Lin Yang , Zhuang Xinguo , Hoang Vanlong , Wu Peng , Luo Xin , Zhang Han , Zhang Xiaoyang
Published: October 2024

Black shales have attracted the attention of numerous researchers not only due to their high potential as hydrocarbon source rocks and shale gas reservoirs, but also to the enrichment of critical metal elements in black shale series. Black shale of the Cambrian Shuijingtuo Formation is one of the most important black shales in the Yangtze platform. This paper conducts integrated research on the mineralogical and geochemical characteristics of this black shale from the Luojiacun section in Western Hubei Region, aiming at elaborating the enrichment mechanism of elevated critical metal elements in the Shuijingtuo black shale. Minerals in the Shuijingtuo black shale are predominantly composed of quartz (avg. 43.0%) and clay minerals (avg. 32.5%), with small proportions of calcite, albite, clinochlore, and pyrite. The Shuijingtuo black shale is characterized by high total organic carbon (TOC, avg. 3.9%) content and enriched in V-Ni-Cr-U and Sr-Ba critical metal assemblages. The elevated V, Cr, Ni, and U present dominant organic affinities, while Sr and Ba are closely correlated to calcite and pyrite, respectively. The enrichment of V-Cr-Ni-U critical element assemblages in Shuijingtuo black shale are ascribed to the high primary productivity, anoxic depositional conditions, marine biologic production, and low-temperature hydrothermal activities. The enrichment of Sr and Ba is related to the high primary productivity and anoxic depositional conditions, respectively.
Exploring the therapeutic potential of “Tianyu” medicine pair in rheumatoid arthritis: an integrated study combining LC-MS/MS, bioinformatics, network pharmacology, and experimental validation
Authors: Tang Lu , Guo Dingyuan , Jia Dongye , Piao Songlan , Fang Chunqiu , Zhu Yueya , Wang Yinghang , Pan Zhi
Published: October 2024

Background

Rheumatoid arthritis (RA) is a widespread chronic autoimmune disease that primarily causes joint inflammation and damage. In advanced stages, RA can result in joint deformities and loss of function, severely impacting patients’ quality of life. The “Tianyu” pair (TYP) is a traditional Chinese medicine formulation developed from clinical experience and has shown some effectiveness in treating RA. However, its role in the complex biological mechanisms underlying RA remains unclear and warrants further investigation.

Methods

We obtained gene sequencing data of synovial tissues from both RA patients and healthy individuals using two gene microarrays, GSE77298 and GSE55235, from the GEO database. Through an integrated approach involving bioinformatics, machine learning, and network pharmacology, we identified the core molecular targets of the “Tianyu” medicine pair (TYP) for RA treatment. Liquid chromatography-mass spectrometry was then employed to analyze the chemical components of TYP. To validate our findings, we conducted animal experiments with Wistar rats, comparing histopathological and key gene expression changes before and after TYP treatment.

Results

Our data analysis suggests that the onset of RA may be associated with inflammation-related immune cells involved in both adaptive and innate immune responses. Potential key targets for TYP treatment in RA include AKR1B10, MMP13, FABP4, NCF1, SPP1, COL1A1, and RASGRP1. Among the components of TYP, Kaempferol, Quercetin, and Salidroside were identified as key, with MMP13 and NCF1 showing the strongest binding affinity to these compounds. Animal experiments confirmed the findings from bioinformatics and network pharmacology, validating the key targets and therapeutic effects of TYP in treating RA.

Conclusion

Our study reveals that TYP has potential clinical value in the treatment of rheumatoid arthritis. This research enhances our understanding of RA’s pathogenesis and provides insight into potential therapeutic mechanisms.
Detoxification of aflatoxin B1 by a Bacillus subtilis spore coat protein through formation of the main metabolites AFQ1 and epi-AFQ1
Authors: Subagia Raditya , Schweiger Wolfgang , Kunz-Vekiru Elisavet , Wolfsberger Dominik , Schatzmayr Gerd , Ribitsch Doris , Guebitz Georg M.
Published: October 2024

A variety of important agricultural crops host fungi from the Aspergillus genus can produce cancerogenic secondary metabolites such as aflatoxins. Consequently, novel strategies for detoxification and their removal from food and feed chains are required. Here, detoxification of Aflatoxin B1 (AFB1) by the Bacillus subtilis multi-copper oxidase CotA (BsCotA) was investigated. This laccase was recombinantly produced in E. coli while codon optimization led to duplication of the amount of active protein obtained. CuCl2 was added to the cultivation medium leading to a 25-fold increase of Vmax corresponding to improved incorporation of Cu2+ into the enzyme protein which is essential for the catalytic reaction. To avoid potential cytotoxicity of Cu2+, cultivation was performed at microaerobic conditions indeed leading to 100x more functional protein when compared to standard aerobic conditions. This was indicated by an increase of Vmax from 0.30 ± 0.02 to 33.56 ± 2.02 U/mg. Degradation kinetics of AFB1 using HPLC with fluorescence detection (HPLC-FLD) analysis indicated a theoretical substrate saturation above solubility in water. At a relatively high concentration of 500 μg/L, AFB1 was decomposed at 10.75 μg/Lh (0.17 nmol*min−1*mg−1) at a dosage of 0.2 μM BsCotA. AFQ1 and epi-AFQ1 were identified as the initial oxidation products according to mass spectrometry (i.e., HPLC-MS, HPLC-QTOF). None of these molecules were substrates for laccase but both decomposed in buffer. However, decomposition does not seem to be due to hydration of the vinyl ether in the terminal furan ring. Genotoxicity of the formed AFB1 was assessed in several dilutions based on the de-repression of the bacterial SOS response to DNA damage indicating about 80-times reduction in toxicity when compared to AFQ1. The results of this study indicate that BsCotA has high potential for the biological detoxification of aflatoxin B1.
Novel HexA splice site mutations in a patient with late atypical onset Tay-Sachs disease: importance of combined NGS and biochemical analysis
Authors: Bilyalova Alina , Shagimardanova Elena , Bilyalov Airat , Zaripova Marina , Shigapova Leyla , Gazizova Guzel , Mazin Pavel , Tatiana Bukina , Gusev Oleg
Published: October 2024

Tay-Sachs disease (TSD) is a rare genetic disorder with diverse clinical manifestations, often leading to underdiagnosis due to symptom similarities with other neurological conditions. In this study, we aimed to identify the genetic mutations underlying late-onset TSD in a 27-year-old patient with progressive neurological symptoms. Whole-exome sequencing revealed two hexA gene mutations associated with TSD: a previously known variant, c.805G > A (p.Gly269Ser), and a novel splice-site mutation, c.346 + 2dupT. Through clinical assessments, genetic analysis, and functional investigations—including RNA sequencing and enzymatic activity assays—we confirmed the pathogenicity of the novel mutation. Our findings highlight the efficacy of advanced genomic technologies in diagnosing intricate genetic disorders and emphasize the significance of functional validation to confirm the effects of mutations. Identifying compound heterozygous mutations in the hexA gene also provides insight into Mendelian inheritance patterns. This case highlights the diagnostic challenges posed by overlapping clinical phenotypes and emphasizes the need for increased genetic awareness among clinicians. Accurate diagnosis of TSD has significant implications for patients and their families, allowing for informed genetic counseling and guiding clinical management decisions. While current treatment options are limited, timely and accurate diagnosis holds promise for future research and therapeutic interventions. This study highlights the value of a multidisciplinary approach in exploring the molecular basis of complex genetic diseases and informing clinical decisions.
Association between advanced lung cancer inflammation index and chronic kidney disease: a cross-sectional study
Authors: Li Xiaotong , Wang Qian , Wu Feng , Ye Ziyang , Li Yafeng
Published: October 2024

Background

Chronic kidney disease (CKD) is one of the common chronic diseases, and malnutrition and inflammation play a key role in the development of CKD. The advanced lung cancer inflammation index (ALI) is a novel index of nutrition and inflammation, and its association with CKD has not yet been clarified. The aim of this study was to explore the potential association between ALI and CKD.

Methods

We conducted a cross-sectional survey using data extracted from the National Health and Nutrition Examination Survey (NHANES, 2003–2018). Weighted multivariate logistic regression was used to assess the association between ALI and CKD, and smoothed curve fitting and threshold effect analyses were used to describe the nonlinear association between ALI and CKD. Subgroup analyses were performed to further assess the influence of other covariates on the relationship between ALI and CKD.

Results

A total of 39,469 adult participants were included in the study, of whom 7,204 (18.25%) were diagnosed with CKD. After adjusting for multiple confounders, we found a significant negative correlation between ALI and CKD (OR = 0.93; 95%CI, 0.91–0.95; p < 0.0001). The risk of CKD tended to decrease with increasing quartiles of ALI. Smoothed curve fitting showed an L-shaped negative correlation between ALI and CKD. Threshold analysis showed a saturation effect of ALI at the inflection point of 55.09. Subgroup analyses and interaction tests showed that this negative association was maintained across age, sex, race, BMI, diabetes, hypertension, cardiovascular disease, and cancer subgroups (P for interaction >0.05).

Conclusion

Our findings suggest a significant correlation between ALI and CKD in the US adult population. However, more large-scale prospective studies are still needed to further confirm our findings.
Microbiota, metabolic profiles and immune biomarkers in infants receiving formula with added bovine milk fat globule membrane: a randomized, controlled trial
Authors: Christensen Chloe , Kok Car Reen , Harris Cheryl L. , Moore Nancy , Wampler Jennifer L. , Zhuang Weihong , Wu Steven S. , Hutkins Robert , Izard Jacques , Auchtung Jennifer M.
Published: October 2024

Introduction

Few studies have evaluated the effects of milk fat globule membrane (MFGM) on microbiota and immune markers in early infant nutrition.

Methods

In this double-blind randomized study, infants (7–18 days of age) received either bovine milk-based infant formula (Control) or similar formula with an added source (5 g/L) of bovine MFGM (INV-MFGM) for 60 days. A reference group received mother’s own human milk over the same period (HM). Oral and stool samples were collected (Baseline and Day 60) to evaluate microbiota, immune markers, and metabolites.

Results

At Day 60, stool bacterial diversity and richness were higher in formula groups vs HM, as were Bifidobacterium bifidum and B. catenulatum abundance. Compared to HM, stool pH was higher in Control, while acetate, propionate, isovalerate, and total short- and branched-chain fatty acids were higher in INV-MFGM. Butyrate and lactate increased for INV-MFGM from baseline to Day 60. No group differences in oral microbiota or immune markers (α- and β-defensin, calprotectin, or sIgA) were detected, although sIgA increased over time in all study groups. Added bovine MFGM in infant formula modulated stool microbiota and short- and branched-chain fatty acids compared to human milk; changes were modest relative to control formula.

Discussion

Overall, distinct patterns of stool metabolites and microbiota development were observed based on early nutrition.

Clinical trial registration

ClinicalTrials.gov, identifier NCT04059666.
Progress of fluorescence imaging in lymph node dissection surgery for prostate and bladder cancer
Authors: Xu Mingquan , Li Panpan , Wei Jinzheng , Yan Pengyu , Zhang Yunmeng , Guo Xinyu , Liu Chao , Yang Xiaofeng
Published: October 2024

Fluorescence imaging is a relatively new imaging method used to visualize different tissue structures to help guide intraoperative operations, which has potential advantages with high sensitivity and contrast compared to conventional imaging. In this work, we review fluorescent contrast agents and devices used for lymphatic system imaging. Indocyanine green is the most widely utilized due to its high sensitivity, specificity, low background fluorescence, and safety profile. In prostate and bladder cancer lymph node dissection, the complex lymphatic drainage can result in missed metastatic nodes and extensive dissection increases the risk of complications like lymphocele, presenting a significant challenge for urologists. Fluorescence-guided sentinel lymph node dissection facilitates precise tumor staging. The combination of fluorescence and radiographic imaging improves the accuracy of lymph node staging. Multimodal imaging presents new potential for precisely identifying metastatic pelvic lymph nodes.
How searcher shoots grow and branch in mature liana mats: the case of Merremia boisiana
Authors: Kuang Qiyu , Su Shiying , Hu Liang
Published: October 2024

The proliferation of vigorous lianas usually forms liana canopies over the crowns of host trees and liana mats on the ground of open areas or large forest gaps. While research on liana canopies has increased significantly in recent decades, our understanding of liana mats remains limited. Merremia boisiana (Convolvulaceae), a fast-growing liana, forms mature liana mats that can persist for decades, characterized by numerous upright searcher shoots that extend from the liana mats in search of supports. However, the reasons behind the proliferation of these searchers, as well as their growth and branching patterns in mature liana mats that lack support, are not well understood. We hypothesize that searchers are an inevitable phase in the growth rhythm of M. boisiana within these mature liana mats. We tested our hypothesis by tracking the lifespan and status of M. boisiana searchers during the early, middle, and late periods of the year. Our findings reveal the following: (1) M. boisiana searchers exhibit apical dominance and have a short lifespan; over 95% of searchers lost their terminal buds within two months during the early period, while it took only one month during the middle and late periods. (2) The original lateral buds of the searchers also have a limited lifespan, yet the nodes can sprout new lateral buds after the loss of their originals. (3) With the withering of terminal buds, the total number of lateral shoots decreased, while the quantity of long lateral shoots (≥ 50 cm) and their elongation rates increased. (4) Each surviving segment of a searcher typically develops one or two long lateral shoots, none of which grow into searchers. We conclude that the shoots of M. boisiana in mature liana mats periodically alternate between searchers and stolons, collectively forming a zigzag branching system. The high rate of lateral bud resprouting may facilitate the rapid recovery of mature liana mats early in the year, while the reduced lifespan of searchers and limited number of long lateral shoots represent effective strategies for M. boisiana, balancing the investment and risk associated with foraging in mature liana mats.
Soil water uptake from different depths of three tree species indicated by hydrogen and oxygen stable isotopes in the permafrost region of Northeast China
Authors: Li Biao , Wu Xiaodong , Dong Xingfeng , Man Haoran , Liu Chao , Zou Siyuan , He Jianxiang , Zang Shuying
Published: October 2024

Global warming has caused the gradual degradation of permafrost, which may affect the vegetation water uptake from different depths. However, the water utilization strategies of different vegetation species during the thawing stages of permafrost regions need further study. To elucidate these differences, we selected the permafrost region in Northeast China as study area. We analyzed the water uptake from different depths of Larix gmelinii, a deciduous coniferous tree, Pinus sylvestris var. mongolica, an evergreen tree, and Betula platyphylla, a deciduous broadleaf tree, using stable isotopes of xylem water, soil water, and precipitation from June to October 2019. The results showed that L. gmelinii primarily used shallow soil water (0-40 cm) with the highest proportion at 64.1%, B. platyphylla generally used middle soil water (40-110 cm) with the highest proportion at 55.7%, and P. sylvestris mainly used middle (40-110cm) and deep soil water (110-150 cm) with the highest proportion at 40.4% and 56.9%. The water sources from different depths exhibited more frequent changes in P. sylvestris, indicating a higher water uptake capacity from different soil depths. L. gmelinii mainly uptakes water from shallow soils, suggesting that the water uptake of this species is sensitive to permafrost degradation. This study revealed the water uptake strategies from different depths of three tree species in a permafrost region, and the results suggested that water uptake capacity of different tree species should be considered in the prediction of vegetation changes in permafrost regions under a warming climate.
Leveraging trait and QTL covariates to improve genomic prediction of resistance to Fusarium head blight in Central European winter wheat
Authors: Morales Laura , Akdemir Deniz , Girard Anne-Laure , Neumayer Anton , Reddy Nannuru Vinay Kumar , Shahinnia Fahimeh , Stadlmeier Melanie , Hartl Lorenz , Holzapfel Josef , Isidro-Sánchez Julio , Kempf Hubert , Lillemo Morten , Löschenberger Franziska , Michel Sebastian , Buerstmayr Hermann
Published: October 2024

Fusarium head blight (FHB) is a devastating disease of wheat, causing yield losses, reduced grain quality, and mycotoxin contamination. Breeding can mitigate the severity of FHB epidemics, especially with genomics-assisted methods. The mechanisms underlying resistance to FHB in wheat have been extensively studied, including phenological traits and genome-wide markers associated with FHB severity. Here, we aimed to improve genomic prediction for FHB resistance across breeding programs by incorporating FHB-correlated traits and FHB-associated loci as model covariates. We combined phenotypic data on FHB severity, anthesis date, and plant height with genome-wide marker data from five Central European winter wheat breeding programs for genome-wide association studies (GWAS) and genomic prediction. Within all populations, FHB was correlated with anthesis date and/or plant height, and a marker linked to the semi-dwarfing locus Rht-D1 was detected with GWAS for FHB. Including the Rht-D1 marker, anthesis date, and/or plant height as covariates in genomic prediction modeling improved prediction accuracy not only within populations but also in cross-population scenarios.