bluuebunny/crossref_metadata_2025 huggingface dataset:
The problem of high water cut in the products of horizontal wells
Authors: Shcherbakova K. O.
Published: March 2023

Background. The production of oil and gas by horizontal wells, despite all its advantages, is subject to exploratory and operational complications. At the final stage of their development, such fields become hard-to-recover reserves. Production of oil and gas is often associated with a high water cut, a significant drop in reservoir pressure, and precipitation of asphaltene deposits.

Aim. To analyze the problem of early indication of flooding of horizontal wells and do research on existing solutions nowadays.

Materials and methods. The dependence of the logarithm of the water-oil ratio on the cumulative oil production was investigated. An analysis of production decline curves was carried out, along with a graphical diagnostics of flooding evolution.

Results. The anticipated cumulative production of a well was determined by continuing the linear dependence to its economic limit. A graph was plotted in semi-logarithmic coordinates for the analysis of production decline curves. According to the dependence of the water-oil ratio versus time, the type of early well flooding was determined in logarithmic coordinates.

Conclusion. One of the most significant problems in the development of horizontal wells consists in the high water cut of the obtained products. According to the data for 2020, the average water cut in the main fields of Russia comprises at least 85%, with the mass ratio of produced oil and associated water approaching 1:7. The use of water-soluble polymers for waterproofing of horizontal wells can be considered a promising direction due to their efficiency in limiting water inflow in vertical and directional wells.
DETERMINATION OF GEOTHERMAL POTENTIAL IN YANKARI GAME RESERVE, BAUCHI STATE, NIGERIA
Authors: Abubakar I. A. , Kure Nicodemus , Daniel H. I. , Afuwai C. G. , Auwal N.
Published: March 2023

The study deals with the determination of geothermal potential of Yankari Game reserve which involves; estimate of the Curie point depth, heat flow and geothermal gradient from spectral analysis of aeromagnetic data covering an area located approximately at longitude 9.7567 oN and Latitude 10.5094 oE. Radially power spectrum was applied to the aeromagnetic data of the study area divided into 4 square blocks and each block analyzed using the spectral centroid method to obtain depth to the top, centroid and bottom of magnetic sources. The depth values were subsequently used to evaluate the Curie-point depth (CPD), geothermal gradient and near-surface heat flow in the study area. The values of the curie point depths (Zb), range from 8.91 km to 10.11 km, with a mean value of 9.71 km, geothermal gradient, range from 57.37 oCkm-1 to 65.10 oCkm-1, with mean value of 60.10 oCkm-1 and heat flow (q), range from 143.43 mWm-2 to 162.75 mWm-2, with a mean value of 150.24 mWm-2. These results entails that the area under study has good geothermal potential for exploration.
ISOLATION AND ANTIMICROBIAL RESISTANCE PHENOTYPE OF Klebsiella pneumonia FROM THE URINE OF SUSPECTED UTI PATIENTS ATTENDING PUBLIC HOSPITALS IN NASARAWA SOUTH SENATORIAL DISTRICT, NASARAWA STATE, NIGERIA
Authors: Ashefo D. P. , Ngwai Y. B. , Ishaleku D.
Published: March 2023

The emergence of antibiotic resistant uropathogenic Klebsiella pnuemoniae is causing major public health crisis worldwide. This study is aimed at Determining the prevalence and antimicrobial resistance phenotypes of the urinary Klebsiella pnuemoniae isolated from patients attending public hospitals in Nasarawa South Senatorial District, Nasarawa State, Nigeria. During the duration of study, urine samples of 375 patients was cultured for the presence of K. pneumonia. A loopful of urine collected in a sterile container was streaked on MacConkey Agar, CLED, and blood agar plates and incubated for 24 hours at 37°C. The identification and resistance to selected antimicrobials were processed in accordance with the approved standards. K. pnuemoniae was found in 38 of the 375 urine samples tested, resulting in an overall prevalence of 10.13%. GHO and GHK shows a lower prevalence of 4.00% each, while DASH demonstrated a higher prevalence of 14.29%. Out-patient (13.19) and females (11.88%) shows higher prevalence of K. pneumonia than in-patient (6.74%) and males (6.14%). Patients aged 25-34 had the highest prevalence (13.82%), while the age group of 54-64 had the lowest prevalence (3.57%). The bacterial isolates demonstrated more resistance to ampicillin (94.74%) and amoxicillin-clavulanic acid (73.6%) compared to cefotaxime (13.16%), ceftriazone (18.42%), ceftazidime and cefoxitin (23.60%), and gentamicin (28.94%). Thirty-three (33) distinct phenotypes were found, with the most common (7.98%) being Ampicillin (AMP), Amoxicillin-Clavulanic acid (AMT), Ciprofloxacin (CIP), Co-trimoxazole (SXT) and Streptomycin (S). The highest multiple antibiotic resistance score (31.57%) is for resistance to three antibiotics, while the lowest (2.63%) is for resistance to one,
EFFECTS OF TEXTILE WASTEWATER PRE-TREATMENT ON LIGNOCELLULOSIC BIOMASS FOR SOLID-STATE ANAEROBIC DIGESTION
Authors: Abubakar M. S. , Yazid A. B. , Sabo A. A. , Ibrahim A. , Aliyu A. U. , Saleh M.
Published: March 2023

Researchers are looking into sustainable and inexpensive energy sources due to the constant rise in the price of fossil fuels, greenhouse gas emissions, and dependence on non-renewable energy sources. In this study, wastewater from the textile industry is co-digested with lignocellulosic biomass (wheat straw) to produce biogas. During 21 days, five anaerobic digesters were run at room temperature (28 to 30 0C). Wheat straw inoculated with cow manure was put into wheat straw operating in five digesters at five different ratios of wastewater to distilled water. It has been discovered that the slurry digested with mere wastewater (not diluted with distilled water) has the lowest production, while the slurry digested with wheat straw and cow dung has the highest production.
PREVALENCE OF Echinococcucus granulosus IN STRAY AND HOME OWNED DOGS IN ADAMAWA STATE, NIGERIA
Authors: Mathias A. , Pukuma S. M. , Enock N.
Published: March 2023

Echinococcosis is a zoonotic larval infection affecting both domestic animals and human with serious health and economic impacts. A study to determine the prevalence of E. granulosus was carried out on dogs from six Local Government Areas (LGA) of Adamawa State. Faecal samples from 384 dogs were collected and screened for the presence of E. granulosus cyst microspically. A structured questionnaire was used and obtained native and exotic data from dog owners. Out of the 384 dog faecal samples, 171 had E. granulosus cyst with overall prevalence of 44.5% where Guyuk LGA had highest prevalence of 53.1% and Michika LGA had a lowest prevalence of 39.1%). With regards to gender, male and female dogs had a prevalence of 30.5% and 32.4% respectively. In terms of season, highest prevalence of 42.7% and lowest prevalence of 33.3% was recorded during rainy and dried season respectively with a significant association (P< 0.05). Un-restricted dogs recorded a prevalence of 66.1% and 38.1% was recorded in restricted dogs with significant relationship (P< 0.05).  Dogs living in suburban areas and kept for security purposes, hunting or guarding have higher chances of infection. Therefore, right and regular treatment of dogs with praziquantel is highly recommended to reduce risk of E. granulosus transmission to humans.
ISOLATION, IDENTIFICATION AND PHYLOGENETIC CHARACTERIZATION OF POTASSIUM-SOLUBILIZING RHIZOBACTERIA ISOLATED FROM THE ROOTS OF Mimosa indica WEED
Authors: Nwokeh U. J. , Okoro I. G. , Orodeji C. U.
Published: March 2023

Most microorganisms residing within plant rhizosphere are of great importance to soil fertility.  The either release plant nutrient into soil solution and make it available for plant absorption directly or indirectly, excrete enzymes or organic acids that facilitate the solubilization of insoluble minerals, such as potassium (K). A laboratory analysis was carried out at the Soil Science Laboratory in Michael Okpara University of Agriculture, Umudike, to isolate potassium-solubilizing rhizobacteria from Mimosa indica a weed that have invaded most agricultural land in the southeastern Nigeria. It was observed that the roots of Mimosaindica had nodules, which is peculiar to legume plants. Two cultivable isolates possessed the ability to solubilize K.  DNA extraction was done and the two bacteria were identified as: Ochrobactrum anthropi and Comamonas testosteroni.  Biochemical tests and Phylogenetic characterization were carried out. Comamonas testosterone gave the highest solubilization efficiency of 650 compared to Ochrobactrum anthropi (325).
O que pensam os futuros professores de Física sobre a inclusão de alunos com deficiência visual? Interpretações a partir da análise textual discursiva
Authors: Santos Thais Cristina dos , Almeida Wesley Dias de , Tonezer Camila
Published: March 2023

Este artigo apresenta uma investigação com licenciandos em Física de uma Universidade da região Oeste do Paraná. O intuito da investigação é interpretar e refletir sobre as percepções dos participantes relacionadas à inclusão de alunos com deficiência visual. Possuímos, como questionamento fenomenológico: o que é Inclusão Escolar de alunos com deficiência visual para licenciandos em Física? Para a coleta dos dados, utilizamos o Formulário Google. Convidamos os futuros professores, por meio de divulgação em mídias sociais; contamos com a participação de quatro estudantes de licenciatura em Física. Analisamos o corpus por meio da metodologia de Análise Textual Discursiva - ATD. Os resultados indicam que, para a efetivação da inclusão, é necessário sensibilização; os participantes ressaltam ser possível promovê-la mesmo com conteúdos mais abstratos, como Física. A inclusão faz parte do ser professor; os licenciandos destacam diferentes definições de inclusão escolar de alunos com deficiência visual.
Experiências grupais com estudantes de um cursinho de educação popular: apontamentos psicanalíticos
Authors: Ribeiro Guilherme Faria , Santeiro Tales Vilela
Published: March 2023

O estudo é uma pesquisa-ação, de enfoque qualitativo, realizada por meio de grupos operativos com sete estudantes de cursinho de educação popular, tendo objetos mediadores como disparadores de diálogos. As experiências são organizadas por meio de emergentes grupais e pensadas com apoio em literatura psicanalítica de processos de grupo de inspiração nas escolas latino-americana e francesa. Três emergentes são observados: (a) o estar só e o possível adoecimento mental frente ao processo de preparo dos estudantes; (b) estratégias de cuidado: o sonhar e o estar em grupo como suportes; e (c) grupo operativo: aprendendo enquanto se trabalha. O trabalho do grupo implicou viver-pensar sobre a importância: do autocuidado no preparo para o vestibular; do sonhar; e de equilibrar o tempo entre atividades de lazer e de estudo. A ampliação dos achados e a descoberta de novas formas de os estudantes se vincularem entre si e com o cursinho dependerão de novos estudos.
SISTEM PAKAR UNTUK MEMPREDIKSI PENYAKIT PADA HEWAN TERNAK SAPI MENGGUNAKAN POHON KEPUTUSAN ID3
Authors: Anggriawan Dicky Anggriawan
Published: March 2023

Banyak peternak sapi memanggil dokter hewan atau mantri hewan untuk memerikasa ternak mereka, namun kesulitan untuk mendatangkan dokter atau mantri tersebut, serta terbatasnya dokter atau mantri yang ada di lingkungan peternak yang menyebabkan sebagian peternak lebih memilih untuk mengatasi dengan caranya sendiri untuk sapi yang sedang sakit. Metode dalam penelitian ini menggunakan metode pohon keputusan ID3. Algoritma ini melakukan pencarian secara menyeluruh (greedy) pada semua kemungkinan pohon keputusan yang berusaha membangun pohon keputusan secara top-down (dari atas ke bawah) mulai dengan pertanyaan: “atribut mana yang pertama kali harus dicek dan diletakkan pada root? ”pertanyaan ini dijawab dengan mengevaluasi semua atribut yang ada dengan menggunakan suatu ukuran statistik yang banyak digunakan adalah information gain untuk mengukur efektivitas suatu atribut dalam mengklasifikasikan kumpulan sampel data. Hasil dari penelitian ini menghasilkan aplikasi sistem pakar berbasis android yang dibangun menggunakan ionic framework ini dapat memudahkan user dalam mendapatkan informasi tentang penyakit sapi dan juga dapat membantu mengetahui penyebab serta cara pengobatan yang sedang diderita sapinya.
PENGEMBANGAN ARAH HADAP ROBOT DAN LINTASAN PERENCANAAN UNTUK KRAKATAU MSL
Authors: Roni Muhammad Noor Azwar
Published: March 2023

Dalam ilmu robotika telah berkembang pesat seiring dengan kemajuan teknologi di Indonesia, dengan kemajuan tersebut dunia robotika mulai banyak yang diminati salah satunya Kontes Robot Sepak Bola Beroda Indonesia yang mengangkat lomba yang bertemakan sepakbola dengan Mobile Robot. Masalah terpenting dalam kontes ini adalah robot harus mampu mencapai sebuah target lintasan tertentu. Robot harus mampu mengetahui besarnya gangguan sehingga robot mampu bergerak kembali ke arah yang aman dan berusaha mendekati target lintasan. Kebanyakan mobile robot tidak mengetahui dimana ia bergerak, bagaimana bergerak di lintasan robot untuk mencapai tujuan dan robot dapat sampai tujuan. Salah satu metode yang populer digunakan untuk mengetahui posisi adalah odometry. Metode odometry penggunaan data dari pergerakan aktuator untuk memperkirakan posisi dari waktu ke waktu. Sensor yang digunakan adalah rotary encoder yang memerlukan roda untuk dapat menentukan posisi dan orientasi robot. Sensor rotary encoder digunakan untuk mencacah pergerakan robot omni pada koordinat x dan y pada proses perhitungan odometry. Namun terdapat kekurangan dalam sensor tersebut yaitu pada saat roda berputar akan mengalami kesalahan perhitungan jika terjadi slip pada roda robot. Oleh karena itu peneliti mengajukan pengembangan arah hadap robot dan lintasan perencanan menggunakan metode dead-reckoning. Dead-reckoning adalah salah satu teknik lokalisasi yang termasuk ke dalam kategori relative localization. Teknik dead-reckoning  banyak digunakan sebagai penelitian fundamental robot bergerak. Teknik ini memanfaatkan hasil data dari sensor optical mouse. Sensor optical mouse merupakan salah satu pilihan untuk mendapatkan hasil yang presisi dari perhitungan yang digunakan. Terdapat beberapa pengujian diantara nya gerak lurus, kekiri, kekanan dan mundur. Hasil dari pengujian dari kelima gerakan bahwa menggunakan prinsip dead-reckoning robot dapat bergerak sesuai dengan target lintasan yang diinginkan dan sama dengan trajectory yang dilewati robot sesungguhnya.
Properties
of green self-compacting concrete designed by particle packing density method
Authors: Vasić Milan , Savić Aleksandar , Martinović Sanja , Vlahović Milica , Volkov-Husović Tatjana
Published: March 2023

Since depletion of natural resources and the amount of construction and demolition waste have overcome the socially and environmentally acceptable level, the construction industry must address this issue and reduce its impact on the environment. A step towards sustainability in the construction industry is the application of recycled aggregates and supplementary cementitious materials as integral components of concretes, which provides conserving natural aggregates and waste reduction. This study adopts a holistic approach to producing green self-compacting concrete with the highest portion of recycled aggregate as a replacement for natural aggregate and fly ash as filler. Based on the particle packing density method, four series of self-compacting concrete were prepared: the first series was made with natural fine and coarse aggregate, the second series was made with fine natural aggregate and recycled coarse aggregate, the third with 50 % (by mass) of fine natural aggregate replaced by recycled fine aggregate and recycled coarse aggregate, and the fourth series completely with recycled fine and coarse aggregate. The content of fly ash remained constant. Regardless of the expected decrease of workability in a fresh state with the increase of the recycled aggregate content, all series exceeded the requirements set for the hardened structural concrete.
Post-pandemic planning: Do we have enough and efficient access to parks?
Authors: Alkhaja Nour , Alawadi Khaled , Ibrahim Hasan Manan
Published: March 2023

Introduction: The COVID-19 pandemic has placed neighborhood parks as a key asset in mitigating the negative implications of extended lockdowns, when parks turned into a sanctuary for residents. With increased scholarly work focusing on developing pots-pandemic neighborhoods, providing access to community parks via efficient routes, is central to such debate. Network connectivity provides a comprehensive assessment of the efficiency of network systems.

Methods: A total of 16 samples, from the city of Abu-Dhabi, have been selected to study their network connectivity, with regard to accessing parks. Three distance-based connectivity measures are used: the pedestrian route directness (PRD), the count of redundant routes Redundancy Count (RC), and the route redundancy index (RI). The samples reflect different street’s typologies and their urban form attributes are quantified.

Results and Discussion: Connectivity analyses results are interrupted with regard to the quantified physical attributes. Findings indicate that gridded, and semi-gridded layouts provide more direct routes to parks, but less route’s redundancy. Conversely, interlocked, and fragmented networks, when having sufficient intersection densities, have less direct routes but more redundancy. The inclusion of alleyways proved to alter typologies into gridded ones and improve both route directness and redundancy. The majority of the selected samples reported sufficient levels of route directness. The current design and planning guidelines, implemented by the Department of Transport and Municipalities are overly descriptive with regard to how neighborhood parks are accessed; therefore, the study’s methodology provides a possible more evidence-based approach to policy development.
Genetic deficiency of protein inhibitor of activated STAT3 suppresses experimental abdominal aortic aneurysms
Authors: Fu Weilai , Liu Haole , Wei Panpan , Xia Congcong , Yu Qingqing , Tian Kangli , Li Yankui , Liu Enqi , Xu Baohui , Miyata Masaaki , Wang Rong , Zhao Sihai
Published: March 2023

Aim

Signal transducer and activator of transcription (STAT) signaling is critical for the pathogenesis of abdominal aortic aneurysms (AAAs). Though protein inhibitor of activated STAT3 (PIAS3) negatively modulates STAT3 activity, but its role in AAA disease remains undefined.

Method

AAAs were induced in PIAS3 deficient (PIAS3−/−) and wild type (PIAS3+/+) male mice via transient intra-aortic elastase infusion. AAAs were assessed by in situ measurements of infrarenal aortic external diameters prior to (day 0) and 14 days after elastase infusion. Characteristic aneurysmal pathologies were evaluated by histopathology.

Results

Fourteen days following elastase infusion, aneurysmal aortic diameter was reduced by an approximately 50% in PIAS3−/− as compared to PIAS3+/+ mice. On histological analyses, PIAS3−/− mice showed less medial elastin degradation (media score: 2.5) and smooth muscle cell loss (media score: 3.0) than those in PIAS3+/+ mice (media score: 4 for both elastin and SMC destruction). Aortic wall leukocyte accumulation including macrophages, CD4+ T cells, CD8+ T cells and B cells as well as mural neovessel formation were significantly reduced in PIAS3−/− as compared to PIAS3+/+ mice. Additionally, PIAS3 deficiency also downregulated the expression levels of matrix metalloproteinases 2 and 9 by 61% and 70%, respectively, in aneurysmal lesion.

Conclusion

PIAS3 deficiency ameliorated experimental AAAs in conjunction with reduced medial elastin degradation and smooth muscle cell depletion, mural leukocyte accumulation and angiogenesis.
Body composition and mortality in a cohort study of Chinese patients with hypertrophic cardiomyopathy
Authors: Zhou Ke , Xiang Jie , Li Guo-yong , Pu Xiao-bo , Zhang Li
Published: March 2023

Objective

To analyse the characteristics and mortality of hypertrophic cardiomyopathy (HCM) patients with different body compositions.

Methods

In this study, 530 consecutive patients with HCM at West China Hospital were studied from November 2008 to May 2016. An equation based on body mass index (BMI) was used to obtain the Percent body fat (BF) and lean mass index (LMI). Patients were divided into five sex-specific BMI, BF and LMI quintiles.

Results

The average BMI, BF and LMI were 23.1 ± 3.2 kg/m2, 28.1 ± 7.3% and 16.5 ± 2.2 kg/m2, respectively. Patients with higher BMI or BF were older and had more symptoms and adverse cardiovascular conditions; those with higher LMI were younger and had less coronary artery disease and lower serum NT-proBNP and creatine. BF correlated positively with resting left ventricular (LV) outflow tract gradient, mitral regurgitation (MR) degree and left atrial diameter but was inversely associated with septal wall thickness (SWT), posterior wall thickness (PWT), LV mass, and E/A ratio; LMI was positively correlated with SWT, LV end diastolic volume and LV mass but was negatively associated with MR degree.48 all-cause deaths occurred during a median follow-up of 33.8 months. Reversed J-shape associations of BMI and LMI with mortality were observed. A lower BMI or LMI was significantly associated with high mortality, especially for low-moderate BMI and LMI. No significant difference in mortality was found across BF quintiles.

Conclusions

The associations of BMI, BF and LMI with baseline characteristics and cardiac remodelling are different in HCM patients. In Chinese HCM patients, low BMI and LMI predicted mortality but not BF.
Causal relationship between polycystic ovary syndrome and chronic kidney disease: A Mendelian randomization study
Authors: Du Yufei , Li Fengao , Li Shiwei , Ding Li , Liu Ming
Published: March 2023

Objective

Polycystic ovary syndrome is one of the most common endocrine disorders among women of childbearing age. The relationship between polycystic ovary syndrome and chronic kidney disease remains unclear and controversial. In this study, we investigated the causal role of polycystic ovary syndrome in the development of chronic kidney disease using the two-sample Mendelian randomization method.

Methods

Public shared summary-level data was acquired from European-ancestry genome wide association studies. We finally obtained 12 single nucleotide polymorphisms as instrumental variables, which were associated with polycystic ovary syndrome in European at genome-wide significance (P < 5 × 10−8). Inverse-variance weighted method was employed in the Mendelian randomization analysis and multiple sensitivity analyses were implemented. Outcome data were obtained from the Open GWAS database.

Results

A positive causal association was observed between polycystic ovary syndrome and chronic kidney disease (odds ratio [OR]=1.180, 95% confidence interval [CI]: 1.038-1.342; P=0.010). Further analyses clarified that causal relationship exist between polycystic ovary syndrome and some serological indicators of chronic kidney disease (fibroblast growth factor 23: OR= 1.205, 95% CI: 1.031-1.409, P=0.019; creatinine: OR= 1.012, 95% CI: 1.001-1.023, P=0.035; cystatin C: OR= 1.024, 95% CI: 1.006-1.042, P=0.009). However, there was no causal association of polycystic ovary syndrome with other factors in the data sources we employed.

Conclusions

Our results indicate an important role of polycystic ovary syndrome in the development of chronic kidney disease. This study suggests that regular follow-up of renal function in patients with polycystic ovary syndrome is necessary for the early treatment of chronic kidney disease.
Taking state of biodiversity reporting into the information age – A South African perspective
Authors: Poole Carol Jean , Skowno Andrew Luke , Currie Jock C. , Sink Kerry Jennifer , Daly Brenda , von Staden Lize
Published: March 2023

South Africa’s National Biodiversity Assessment (NBA) is the primary tool for monitoring and reporting on the state of biodiversity, with a focus on spatial information and key indicators. The NBA distills information that informs policies and strategies, meets national and international reporting requirements, and helps prioritize limited resources for managing and conserving biodiversity. The three previous versions of the NBA (2004, 2011 and 2018) are in the form of detailed thematic technical reports and a synthesis report, served on a simple, static web page. Selected spatial products from the report are available via a dedicated web platform (http://nba.sanbi.org.za/). While all methods and data are clearly described in the technical reports, most of the underlying analyses are inaccessible, lacking reproducibility and transparency. This makes iterative updates to indicators or metrics challenging and inefficient, complicates version control, and exacerbates the risk of capacity, knowledge and data loss during staff turnover. To move the assessment process into the information age we aim to develop well documented and reproducible workflows, and to serve the indicators and their accompanying synthesis on an interactive web platform that facilitates uptake. Achieving these aims will deliver efficiency, greater transparency and trust in future NBA products and will strengthen communication and engagement with the content by the many different users of those products. While these visions will not be realized overnight, the skills and systems required to achieve them can be adaptively built towards an improved NBA that better serves the needs of our society.
Molecular HLA mismatching for prediction of primary humoral alloimmunity and graft function deterioration in paediatric kidney transplantation
Authors: Kim Jon Jin , Fichtner Alexander , Copley Hannah C. , Gragert Loren , Süsal Caner , Dello Strologo Luca , Oh Jun , Pape Lars , Weber Lutz T. , Weitz Marcus , König Jens , Krupka Kai , Tönshoff Burkhard , Kosmoliaptsis Vasilis
Published: March 2023

Introduction

Rejection remains the main cause of allograft failure in paediatric kidney transplantation and is driven by donor-recipient HLA mismatching. Modern computational algorithms enable assessment of HLA mismatch immunogenicity at the molecular level (molecular-mismatch, molMM). Whilst molMM has been shown to correlate with alloimmune outcomes, evidence demonstrating improved prediction performance against traditional antigen mismatching (antMM) is lacking.

Methods

We analysed 177 patients from the CERTAIN registry (median follow-up 4.5 years). molMM scores included Amino-Acid-Mismatch-Score (AAMS), Electrostatic-Mismatch-Score (EMS3D) and netMHCIIpan (netMHC1k: peptide binding affinity ≤1000 nM; netMHC: binding affinity ≤500 nM plus rank <2%). We stratified patients into high/low-risk groups based on risk models of DSA development.

Results

Donor-specific HLA antibodies (DSA) predominantly targeted the highest scoring molMM donor antigen within each HLA locus. MolMM scores offered superior discrimination versus antMM in predicting de novo DSA for all HLA loci; the EMS3D algorithm had particularly consistent performance (area under the receiver operating characteristic curve (AUC) >0.7 for all HLA loci vs. 0.52-0.70 for antMM). ABMR (but not TCMR) was associated with HLA-DQ molMM scores (AAMS, EMS3D and netMHC). Patients with high-risk HLA-DQ molMM had increased risk of graft function deterioration (50% reduction in baseline eGFR (eGFR50), adjusted HR: 3.5, 95% CI 1.6-8.2 high vs. low EMS3D). Multivariable modelling of the eGFR50 outcome using EMS3D HLA-DQ stratification showed better discrimination (AUC EMS3D vs. antMM at 2 years: 0.81 vs. 0.77, at 4.5 years: 0.72 vs. 0.64) and stratified more patients into the low-risk group, compared to traditional antMM.

Conclusion

Molecular mismatching was superior to antigen mismatching in predicting humoral alloimmunity. Molecular HLA-DQ mismatching appears to be a significant prognostic factor for graft function deterioration in paediatric kidney transplantation.
The relationship between autophagy and PD-L1 and their role in antitumor therapy
Authors: Cui Yu , Shi Jinfeng , Cui Youbin , Zhu Zhanpeng , Zhu Wei
Published: March 2023

Immune checkpoint blockade therapy is an important advance in cancer treatment, and the representative drugs (PD-1/PD-L1 antibodies) have greatly improved clinical outcomes in various human cancers. However, since many patients still experience primary resistance, they do not respond to anti-PD1/PD-L1 therapy, and some responders also develop acquired resistance after an initial response. Therefore, combined therapy with anti-PD-1/PD-L1 immunotherapy may result in better efficacy than monotherapy. In tumorigenesis and tumor development processes, the mutual regulation of autophagy and tumor immune escape is an intrinsic factor of malignant tumor progression. Understanding the correlation between the tumor autophagy pathway and tumor immune escape may help identify new clinical cancer treatment strategies. Since both autophagy and immune escape of tumor cells occur in a relatively complex microenvironmental network, autophagy affects the immune-mediated killing of tumor cells and immune escape. Therefore, comprehensive treatment targeting autophagy and immune escape to achieve “immune normalization” may be an important direction for future research and development. The PD-1/PD-L1 pathway is essential in tumor immunotherapy. High expression of PD-L1 in different tumors is closely related to poor survival rates, prognoses, and treatment effects. Therefore, exploring the mechanism of PD-L1 expression is crucial to improve the efficacy of tumor immunotherapy. Here, we summarize the mechanism and mutual relationship between autophagy and PD-L1 in antitumor therapy, which may help enhance current antitumor immunotherapy approaches.
Establishing a human bone marrow single cell reference atlas to study ageing and diseases
Authors: Lee Nicole Yee Shin , Li Mengwei , Ang Kok Siong , Chen Jinmiao
Published: March 2023

Introduction

Ageing in the human bone marrow is associated with immune function decline that results in the elderly being vulnerable to illnesses. A comprehensive healthy bone marrow consensus atlas can serve as a reference to study the immunological changes associated with ageing, and to identify and study abnormal cell states.

Methods

We collected publicly available single cell transcriptomic data of 145 healthy samples encompassing a wide spectrum of ages ranging from 2 to 84 years old to construct our human bone marrow atlas. The final atlas has 673,750 cells and 54 annotated cell types.

Results

We first characterised the changes in cell population sizes with respect to age and the corresponding changes in gene expression and pathways. Overall, we found significant age-associated changes in the lymphoid lineage cells. The naïve CD8+ T cell population showed significant shrinkage with ageing while the effector/memory CD4+ T cells increased in proportion. We also found an age-correlated decline in the common lymphoid progenitor population, in line with the commonly observed myeloid skew in haematopoiesis among the elderly. We then employed our cell type-specific ageing gene signatures to develop a machine learning model that predicts the biological age of bone marrow samples, which we then applied to healthy individuals and those with blood diseases. Finally, we demonstrated how to identify abnormal cell states by mapping disease samples onto the atlas. We accurately identified abnormal plasma cells and erythroblasts in multiple myeloma samples, and abnormal cells in acute myeloid leukaemia samples.

Discussion

The bone marrow is the site of haematopoiesis, a highly important bodily process. We believe that our healthy bone marrow atlas is a valuable reference for studying bone marrow processes and bone marrow-related diseases. It can be mined for novel discoveries, as well as serve as a reference scaffold for mapping samples to identify and investigate abnormal cells.
Mapping the SLP76 interactome in T cells lacking each of the GRB2-family adaptors reveals molecular plasticity of the TCR signaling pathway
Authors: Ruminski Kilian , Celis-Gutierrez Javier , Jarmuzynski Nicolas , Maturin Emilie , Audebert Stephane , Malissen Marie , Camoin Luc , Voisinne Guillaume , Malissen Bernard , Roncagalli Romain
Published: March 2023

The propagation and diversification of signals downstream of the T cell receptor (TCR) involve several adaptor proteins that control the assembly of multimolecular signaling complexes (signalosomes). The global characterization of changes in protein-protein interactions (PPI) following genetic perturbations is critical to understand the resulting phenotypes. Here, by combining genome editing techniques in T cells and interactomics studies based on affinity purification coupled to mass spectrometry (AP-MS) analysis, we determined and quantified the molecular reorganization of the SLP76 interactome resulting from the ablation of each of the three GRB2-family adaptors. Our data showed that the absence of GADS or GRB2 induces a major remodeling of the PPI network associated with SLP76 following TCR engagement. Unexpectedly, this PPI network rewiring minimally affects proximal molecular events of the TCR signaling pathway. Nevertheless, during prolonged TCR stimulation, GRB2- and GADS-deficient cells displayed a reduced level of activation and cytokine secretion capacity. Using the canonical SLP76 signalosome, this analysis highlights the plasticity of PPI networks and their reorganization following specific genetic perturbations.
Linguistic and ontological challenges of multiple domains contributing to transformed health ecosystems
Authors: Kreuzthaler Markus , Brochhausen Mathias , Zayas Cilia , Blobel Bernd , Schulz Stefan
Published: March 2023

This paper provides an overview of current linguistic and ontological challenges which have to be met in order to provide full support to the transformation of health ecosystems in order to meet precision medicine (5 PM) standards. It highlights both standardization and interoperability aspects regarding formal, controlled representations of clinical and research data, requirements for smart support to produce and encode content in a way that humans and machines can understand and process it. Starting from the current text-centered communication practices in healthcare and biomedical research, it addresses the state of the art in information extraction using natural language processing (NLP). An important aspect of the language-centered perspective of managing health data is the integration of heterogeneous data sources, employing different natural languages and different terminologies. This is where biomedical ontologies, in the sense of formal, interchangeable representations of types of domain entities come into play. The paper discusses the state of the art of biomedical ontologies, addresses their importance for standardization and interoperability and sheds light to current misconceptions and shortcomings. Finally, the paper points out next steps and possible synergies of both the field of NLP and the area of Applied Ontology and Semantic Web to foster data interoperability for 5 PM.
Temporal dynamics of geothermal microbial communities in Aotearoa-New Zealand
Authors: Power Jean F. , Lowe Caitlin L. , Carere Carlo R. , McDonald Ian R. , Cary S. Craig , Stott Matthew B.
Published: March 2023

Microbial biogeography studies, in particular for geothermal-associated habitats, have focused on spatial patterns and/or individual sites, which have limited ability to describe the dynamics of ecosystem behaviour. Here, we report the first comprehensive temporal study of bacterial and archaeal communities from an extensive range of geothermal features in Aotearoa-New Zealand. One hundred and fifteen water column samples from 31 geothermal ecosystems were taken over a 34-month period to ascertain microbial community stability (control sites), community response to both natural and anthropogenic disturbances in the local environment (disturbed sites) and temporal variation in spring diversity across different pH values (pH 3, 5, 7, 9) all at a similar temperature of 60–70°C (pH sites). Identical methodologies were employed to measure microbial diversity via 16S rRNA gene amplicon sequencing, along with 44 physicochemical parameters from each feature, to ensure confidence in comparing samples across timeframes. Our results indicated temperature and associated groundwater physicochemistry were the most likely parameters to vary stochastically in these geothermal features, with community abundances rather than composition more readily affected by a changing environment. However, variation in pH (pH ±1) had a more significant effect on community structure than temperature (±20°C), with alpha diversity failing to adequately measure temporal microbial disparity in geothermal features outside of circumneutral conditions. While a substantial physicochemical disturbance was required to shift community structures at the phylum level, geothermal ecosystems were resilient at this broad taxonomic rank and returned to a pre-disturbed state if environmental conditions re-established. These findings highlight the diverse controls between different microbial communities within the same habitat-type, expanding our understanding of temporal dynamics in extreme ecosystems.
Eurypsychrophilic acidophiles: From (meta)genomes to low-temperature biotechnologies
Authors: Dopson Mark , González-Rosales Carolina , Holmes David S. , Mykytczuk Nadia
Published: March 2023

Low temperature and acidic environments encompass natural milieus such as acid rock drainage in Antarctica and anthropogenic sites including drained sulfidic sediments in Scandinavia. The microorganisms inhabiting these environments include polyextremophiles that are both extreme acidophiles (defined as having an optimum growth pH < 3), and eurypsychrophiles that grow at low temperatures down to approximately 4°C but have an optimum temperature for growth above 15°C. Eurypsychrophilic acidophiles have important roles in natural biogeochemical cycling on earth and potentially on other planetary bodies and moons along with biotechnological applications in, for instance, low-temperature metal dissolution from metal sulfides. Five low-temperature acidophiles are characterized, namely, Acidithiobacillus ferriphilus, Acidithiobacillus ferrivorans, Acidithiobacillus ferrooxidans, “Ferrovum myxofaciens,” and Alicyclobacillus disulfidooxidans, and their characteristics are reviewed. Our understanding of characterized and environmental eurypsychrophilic acidophiles has been accelerated by the application of “omics” techniques that have aided in revealing adaptations to low pH and temperature that can be synergistic, while other adaptations are potentially antagonistic. The lack of known acidophiles that exclusively grow below 15°C may be due to the antagonistic nature of adaptations in this polyextremophile. In conclusion, this review summarizes the knowledge of eurypsychrophilic acidophiles and places the information in evolutionary, environmental, biotechnological, and exobiology perspectives.
Biocontrol potential of lipopeptides produced by the novel Bacillus subtilis strain Y17B against postharvest Alternaria fruit rot of cherry
Authors: Ahmad Tanvir , Xing Fuguo , Nie Chengrong , Cao Changyu , Xiao Ying , Yu Xi , Moosa Anam , Liu Yang
Published: March 2023

The use of synthetic fungicides against postharvest Alternaria rot adversely affects human health and the environment. In this study, as a safe alternative to fungicides, Bacillus subtilis strain Y17B isolated from soil exhibited significant antifungal activity against Alternaria alternata. Y17B was identified as B. subtilis based on phenotypic identification and 16S rRNA sequence analysis. To reveal the antimicrobial activity of this strain, a PCR-based study detected the presence of antifungal lipopeptide (LP) biosynthetic genes from genomic DNA. UPLC Q TOF mass spectrometry analysis detected the LPs surfactin (m/z 994.64, 1022.68, and 1026.62), iturin (m/z 1043.56), and fengycin (m/z 1491.85) in the extracted LP crude of B. subtilis Y17B. In vitro antagonistic study demonstrated the efficiency of LPs in inhibiting A. alternata growth. Microscopy (SEM and TEM) studies showed the alteration of the morphology of A. alternata in the interaction with LPs. In vivo test results revealed the efficiency of LPs in reducing the growth of the A. alternata pathogen. The overall results highlight the biocontrol potential of LPs produced by B. subtilis Y17B as an effective biological control agent against A. alternata fruit rot of cherry.
Multimodality neuroimaging in vascular mild cognitive impairment: A narrative review of current evidence
Authors: Liu Qiuping , Zhang Xuezhu
Published: March 2023

The vascular mild cognitive impairment (VaMCI) is generally accepted as the premonition stage of vascular dementia (VaD). However, most studies are focused mainly on VaD as a diagnosis in patients, thus neglecting the VaMCI stage. VaMCI stage, though, is easily diagnosed by vascular injuries and represents a high-risk period for the future decline of patients’ cognitive functions. The existing studies in China and abroad have found that magnetic resonance imaging technology can provide imaging markers related to the occurrence and development of VaMCI, which is an important tool for detecting the changes in microstructure and function of VaMCI patients. Nevertheless, most of the existing studies evaluate the information of a single modal image. Due to the different imaging principles, the data provided by a single modal image are limited. In contrast, multi-modal magnetic resonance imaging research can provide multiple comprehensive data such as tissue anatomy and function. Here, a narrative review of published articles on multimodality neuroimaging in VaMCI diagnosis was conducted，and the utilization of certain neuroimaging bio-markers in clinical applications was narrated. These markers include evaluation of vascular dysfunction before tissue damages and quantification of the extent of network connectivity disruption. We further provide recommendations for early detection, progress, prompt treatment response of VaMCI, as well as optimization of the personalized treatment plan.
Examination of brain area volumes based on voxel-based morphometry and multidomain cognitive impairment in asymptomatic unilateral carotid artery stenosis
Authors: Duan Wei , Lu Li , Cui Chun , Shu Tongsheng , Duan Dazhi
Published: March 2023

Objective

Recent evidence has demonstrated that unilateral carotid artery stenosis (CAS) can contribute to the development of cognitive impairment. However, the features of cognitive dysfunction induced by unilateral CAS remain unclear.

Methods

Sixty asymptomatic patients with unilateral CAS were divided into mild, moderate and severe stenosis groups. These patients and 20 healthy controls provided clinical data and serum, which was used to assess the levels of certain vascular risk factors. Then, they participated in a battery of neuropsychological tests. Additionally, all participants underwent a 3.0 T magnetic resonance imaging (MRI) scan of the brain. Chi-square tests and one-way ANOVA were used to determine significant differences in the risk factors and cognitive test scores between groups. Multiple logistic regression analysis and the receiver operating characteristic (ROC) curve analysis were performed to identify the independent risk factors for cognitive impairment in patients with CAS. Finally, fluid attenuated inversion recovery (FLAIR) T1-weighted MRI images were processed by voxel-based morphometry (VBM) analysis using the Statistical Parametric Mapping (SPM) 8 software.

Results

Compared with healthy controls, the scores of the Mini-Mental State Examination, Digital Span Test backward, and Rapid Verbal Retrieve were significantly reduced in patients with left CAS. The scores in all cognitive scales were significantly lower in patients with right CAS than in controls. Logistic regression analysis demonstrated that the degree of carotid stenosis was an independent risk factor for cognitive impairment in asymptomatic patients with unilateral CAS. Furthermore, VBM analysis showed that, compared with those in healthy controls, gray matter and white matter volumes in specific brain areas were markedly decreased in patients with severe unilateral CAS. However, in patients with moderate right CAS, there was a significant decline in the volume of gray matter in the left parahippocampal gyrus and supplementary motor area. Additionally, the volume of white matter in the left insula was obviously lower in patients with moderate right CAS than in healthy controls.

Conclusion

Unilateral asymptomatic CAS, especially on the right side, contributed to cognitive impairment, including memory, language, attention, executive function and visuospatial function. In addition, based on VBM analysis, both gray matter atrophy and white matter lesions were found in patients with unilateral asymptomatic CAS.
Real-world experience of sorafenib maintenance after allogeneic hematopoietic stem cell transplantation for FLT3-ITD AML reveals high rates of toxicity-related treatment interruption
Authors: Morin Sarah , Giannotti Federica , Mamez Anne-Claire , Pradier Amandine , Masouridi-Levrat Stavroula , Simonetta Federico , Chalandon Yves
Published: March 2023

Sorafenib significantly improves survival of FLT3-ITD mutated AML patients when used as a post-allogeneic HSCT maintenance. Importantly, clinical trials reported a low rate of toxicities requiring sorafenib discontinuation. The aim of our analysis was to evaluate the real-world experience in patients treated with post-allogeneic HSCT sorafenib maintenance therapy for FLT3-ITD AML with a particular focus on tolerability and toxicity-related treatment interruption. We conducted a single-center retrospective study on 30 FLT3-ITD AML patients undergoing allogeneic HSCT in complete remission between 2017 and 2020 and who received sorafenib maintenance. 26 patients (87%) experienced toxicities leading to dose reduction (n=9) or direct interruption (n=17). Average time on sorafenib was 125 days (range 1-765). Most common toxicities were skin, gastrointestinal, and hematologic. Among patients who had a dose reduction, 4 eventually interrupted the drug and 5 were able to continue. Among patients who interrupted sorafenib because of toxicities, 7 were re-challenged with good tolerance in 3 cases. Overall, 18 patients (60% of the entire cohort) definitively discontinued sorafenib because of toxicities. 14 patients were thereafter switched to midostaurin. Importantly, with a median follow-up of 12 months, the median overall survival was not reached suggesting a positive impact of sorafenib maintenance despite the high rates of treatment interruption. In conclusion, our real-world analysis reveals high rates of toxicity-related interruption of sorafenib maintenance after allogeneic HSCT. Interestingly, our results suggest the feasibility of re-challenging with sorafenib and/or of switching to other maintenance approaches in case of intolerance.