bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of obstetric complications in pregnant women in Osisioma-NgwaLocal Government Area, (LGA). Abia State, Nigeria
Authors: Ndubueze Onyemachi Prince Ezenwa
Published: March 2024

Background: Complications during pregnancy and childbirth are leading causes of death and disability among women of reproductive age in developing countries even though majority of these deaths are due to preventable causes; consequently, improving maternal health is one of the Millennium Development Goals with a target of 75% reduction in maternal deaths by 2015. Objective: To determine the prevalence of obstetric complications in both orthodox and un-orthodox health care in Osisioma-Ngwa LGA., Abia state, Nigeria. Methods and Materials: A descriptive cross-sectional study carried out in Osisioma-Ngwa LGA,Abia State, among 431 women of child bearing age selected using systemic sampling method. Data were collected using a self- administered questionnaire; data analysis was done using Statistical Package for Social Sciences (SPSS) version 26. Result: Out of the 431 participants in the study, there was 384 (90%) response rate, 178 (46.40%) had Ante-natal Care (ANC) in non-orthodox centers, whereas 206 (53.60%) had ANC in orthodox centers. One hundred and twenty-one (31.50%) delivered their babies outside a hospital setting and 263 (68.50%) had their babies in orthodox setting. Out of 92 (24.40%) of those who had problem during pregnancy, 51 (55.43%) of them had ANC outside a hospital setting while 41 (44.57%) used the hospital ANC. These problems were hypertension 22 (23.91%) and bleeding 70 (76.09%). Also, out of 231 (60.20%) of those who had problem during delivery or immediately after, 119 (51.52%) delivered outside a hospital setting. Prevalence of complication is 13.28% from non-orthodox centres against 10.68% from orthodox centres. The major problems included; bleeding per vaginum 120 (31.25%), failure to progress in labor 53 (13.80%), fever 51 (13.28%). Conclusion: The findings in this study suggest the importance of strengthening maternal and child health policies in the state. The prevalence of obstetric complications is higher with the patronage of non-orthodox obstetric care facilities.
Peeler core and slabwood fibre properties for Pinus radiata D.Don pulp production
Authors: Elissetche Juan Pedro , Apiolaza Luis A. , Alzamora Rosa M. , Soto Luis O. , Lasserre Jean Pierre
Published: March 2024

Background: Pulp production based on Pinus radiata D.Don is constantly improving the value recovery of logs. One example is using the peeler cores and slabwood derived from sawing and peeling processes to produce pulp. However, these two raw materials have not been characterised for their fibre properties. 
Methods: We report on four wood fibre quality attributes derived from peeler cores and slabwood, directly influencing pulp quality and pulping process: fibre length (mm), fibre width (µm), fines content (%), and coarseness (µg/m). This pilot study sampled two P. radiata stands grown on different sites and early silvicultural regimes in the Araucanía Region of Chile. Analysis of wood fibre consisted of three trees per stand, and six discs per tree: two at the bottom, two at breast height (1.3 m), and the last two at 5.23 m height. 
Results: The trajectory of mean annual increment in diameter at breast height (MAI) and periodic annual increment in diameter at breast height (PAI) for trees in the two stands aligned with their respective site qualities and silvicultural regimes. In Stand 1, with a site index of 36, and Stand 2, with a site index of 31, the average proportions of juvenile wood (measured at 1.3 m) were 50% and 53%, respectively. Thus, despite weed control and fertiliser application in Stand 1, there was no increase observed in the proportion of juvenile wood. There were significant differences in fibre properties between peeler core and slabwood, and these differences were present across the range of tree heights and diameters (p<0.05). While there were no statistically significant differences among disc positions, significant distinctions emerged between stands and wood types. The interaction between these factors was also found to be statistically significant (p<0.05).
Conclusions: Our study suggests that adding these two materials into the mix for producing pulp would have positive implications due to pulp from peeler core is more suitable for printing and writing grades and addition of mature wood from slabwood, could improve strength properties of paper manufacture. However, it is necessary to test the optimal proportion for the final mix.
Just a touch away
Authors:   , Meijer Larissa Lauren
Published: March 2024

In this thesis I aimed to investigate whether CT-optimal touch can ameliorate pain and itch in healthy individuals as well as in Parkinson patients suffering
from chronic pain. I created a novel model, used experimental studies, a casereport and a longitudinal study to understand the underlying mechanisms of
CT-optimal touch and its interaction with pain processing. I show that CT-optimal touch can ameliorate chronic pain, that it might be used when immediate pain relief is needed and that it is feasible to implement in daily-routine. Furthermore, CT-optimal touch can also reduce electrically induced itch. In addition, I show that the ameliorating effect of CT-optimal touch is independent of the perceived pleasantness. This further emphasizes that it is necessary to differentiate between CT-optimal touch and affective touch, which is substantiated by Case et al. (2023) and Schirmer et al. (2023). Furthermore, the results of an online study showed that people who feel
touch deprived, report to observe touch as more pleasant. We also show that this has negative consequences for our general well-being (Hasenack, Meijer, Kamps,
et al., 2023). As feeling touch deprived can have a negative impact on our mental health, this is relevant for the post-COVID-19 period as well. It also further
emphasizes the importance of receiving touch frequently. Taken together, this thesis further substantiates the importance of promoting receiving as well as providing CT-optimal touch as it appears to have many beneficial effects. Important first steps of implementing CT-optimal touch as a new non-pharmacological pain treatment are provided here as well. Expanding our current knowledge on the neurophysiology behind this type of touch and its interaction with pain and itch is a necessity for our
further understanding.
Caesarean Hysterectomy for Placenta Accreta Spectrum in a Single Centre: A Series of 19 Cases
Authors: Bhanumathy Presannakumari , Balachandran Divya Mecheril , Cleetus Nirpin , Hassan Jesna , Pappachan Skariah , G.K Libu
Published: March 2024

The objective of this study is to assess obstetric complications, blood loss, blood transfusion requirement, and maternal and fetal outcomes associated with the authors’ approach of Caesarean hysterectomy for placenta accreta spectrum disorders. Data were collected from case records of all females who underwent Caesarean hysterectomy between August 2013–August 2023 at Lifeline Multispeciality Hospital, Adoor, Kerala, India. There were 19 cases of Caesarean hysterectomy. The mean age was 33.63±2.90 years. Mean blood loss during surgery was 1.11±0.16 L, and the mean packed red blood cells transfused was 2.00±0.38 units. The mean gestational age of termination was 33 weeks and 5 days, and mean birth weight was 2.28±0.21 kg. There were no maternal or neonatal deaths. Placenta accreta spectrum should be managed in a multidisciplinary setup with the involvement of a senior experienced obstetrician. Early, careful bladder dissection before proceeding with hysterectomy will help in reducing haemorrhage, and in accelerating hysterectomy.
UJI AKTIVITAS EKSTRAK METANOL BIJI JUWET (SYZYGIUM CUMINI (L.) SKEELS) SEBAGAI ANTIHIPERURISEMIA PADA MENCIT HIPERURISEMIA
Authors: Ulya Tuhfatul , Masruroh Ika Nur , Muslichah Siti , Ningsih Indah Yulia
Published: March 2024

The purpose of this research was to study the activity of Syzygium cumini seed extract as antihyperuricemics agents on hyperuricemic male Balb-C mice. Twenty four male mice were divided into 6 groups, i.e the first group as a normal control K(N); the second group as a negative control K(-) was treated with CMC Na 1% 0,2 ml/20g/BW orally; the third group as a positive control K(+) was treated with allopurinol 10 mg/kg BW orally; the fourth to sixth groups (P1, P2, and P3) were treated with 200, 400, and 800 mg/kg BW methanol extract of Syzygium cumini seed orally for 8 days. Inducing performed using chicken liver juice 0,2 % b/v for 4 days, melinjo 10 % b/b of standart feed mice for 12 days, and potassium oxonate 250 mg/kg BW i.p was induced in 2 hours before the blood samples collection. The blood samples was taken from vena ophtalmicus. The concentration of uric acid was determined with FS DHBSA. Data was analyzed using One Way Anova dan LSD test. The result showed that activity of methanol extract of Syzygium cumini seed has significant effect (p<0,05) in reducing the concentration of uric acid in mice. The substances estimated has antihyperuricemic activity were flavonoid, alkaloid, terpenoid, saponin, and tanin.
UJI EFEKTIVITAS ANTIINFLAMASI EKSTRAK ETANOL KOMBINASI DAUN KEMANGI LOMBOK (Ocimum sanctum) DAN DAUN SALAM (Syzygium polyanthum) PADA TIKUS JANTAN
Authors: Putri Susi Windi Ana , Pertiwi Ajeng Dian , Rahmawati Sri , Idawati Sri
Published: March 2024

Inflamasi merupakan respon tubuh terhadap cedera jaringan dan infeksi, sehingga menginaktifasi atau merusak organisme yang menyerang. Menghilangkan zat iritan, dan mengatur derajat perbaikan jaringan. Lima khas cirri dari inflamasi atau biasa dikenal sebagai tanda-tanda utama inflamasi yaitu kemerahan (rubor), panas (kalor), pembekakan (tumor), nyeri/sakit (dolor) dan hilangnya fungsi  (fungsiolaesa)

Penelitian ini bertujuan untuk mengetaui efek dari inflmasi ekstrak etanol kombinasi daun kemangi lombok (Ocimum Sanctum) daun salam (Syzygium Polyanthum) pada tikus jantan yang dinduksi dengan caragen 0,1%. Penelitian ini melakukan 15 ekor tikus jantan dan dibagi menjadi 5 kelompok, kelompok I diberikan Nacmc sebagai kontrol (positif), kelompok II diberikan Natrium Diclofenac sebagai kontrol (Negatif), kelompok III diberikan estrak etanol kombinasi daun kemangi lombok dan daun salam dengan dosis 125:125 mg/ kg bb, kelompok IV diberikan ekstrak etanol kombinasi daun kemangi lombok dan daun salam dengan dosis 125:75mg/ kg bb, dan kelompok V diberikan ekstrak etanol kombinasi daun kemangi lombok dan daun salam dengan dosis 250:75mg/ kg bb. Seluruh pemberian dilakukan secara oral, dan pengukuran kaki tikus jantan dilakukan setiap 30 menit sampai 150 menit. Data dianalisis secara statistik menggunakan one way anova dilanjutkan dengan uji LSD untuk melihat antar perlakuan. Hasil penelitian menunjukan bahwa dosis 250:75 memiliki efek untuk menurunkan jumlah volume udem yang terjadi pada tikus jantan.
EVALUATION OF HIGH ALERT DRUG MANAGEMENT AT THE SITI HAJAR MATARAM ISLAMIC HOSPITAL
Authors: Septiana Wahyu , Utami Evi Fatmi , Purmafitriah En , Hardani Hardani
Published: March 2024

Pengelolaan obat merupakan salah satu kegiatan pelayanan kefarmasian yang bersifat manajerial yang meliputi tahapan seleksi, perencanaan, pengadaan, penyimpanan, pendistribusian, pemusnahan, evaluasi, pencatatan dan pelaporan dengan memanfaatkan sumber yang tersedia. Tujuan : Untuk mengetahui proses pengelolaan obat di Rumah Sakit Islam Siti Haja Kota Mataram Tahun 2022. Metode : Metode yang digunakan dalam penelitian ini adalah lembar observasi dan pedoman wawancara dengan langkah-langkah pengumpulan data yang dilakukan terutama dengan melakukan di -wawancara mendalam dan terbuka, data sekunder diperoleh dari data inventaris dan laporan dari Instalasi Farmasi RS Islam Siti Hajar Mataram. Hasil : Berdasarkan hasil wawancara dengan penanggung jawab Rumah Sakit Islam Siti Hajar Mataram bahwa obat Hight Alert yang meliputi 19 obat adalah : Meylon, MgSo4, Dektro, Potassium klorida/KCL, Infus saline ostu, Digoxin, Gliquidone, Glimepirede, Metformin, Propasolol, Acar bos, Alganax, Alupurinol, Valisanbe, Venobarbital, Neuridal. Prohiper, Clobazam, Zudem. Kesimpulan : Evaluasi Pengelolaan Obat High Alert di RS Islam Siti Hajar Mataram menyatakan bahwa pengelolaan obat high alert di rumah sakit telah dilaksanakan sesuai dengan pedoman Menteri Kesehatan No.72 Tahun 2016.
Sanctions and Democracy: The Limits of Peace
Authors: Walentek Dawid
Published: March 2024

Scholars have argued whether democratic peace also holds in the realm of economic sanctions – whether there is an economic peace. Substantial amount of evidence has been gathered both for and against economic peace. This article provides a new insight, with the use of the updated TIES data set on sanctions and two data sets on democracy (Polity IV and V-Dem), into the topic of economic peace. It finds that democracies are both more likely to issue economic sanctions and that there is no economic peace. In fact, the opposite holds and democracies are more likely to sanction one another. This study indicates that economic coercion in international relations is driven by the constraints and incentives that public opinion and interests groups place on democratic leaders.
Algorithm for Providing Geriatric and Gerontological Care based on International Experience
Authors: YERMUKHANOVA Lyudmila , KIMATOVA Kerbez , SARSENBAYEVA Gulzat , SEIDAKHMETOVA Aizat , ABDIKADIROVA Indira
Published: March 2024

The relevance of the stated topic of this research is conditioned upon the numerous problems of providing medical care to elderly people who suffer from chronic diseases characteristic of various disability groups, accompanied by a complete or partial loss of the ability to self-care, as a result of which there is a steady trend towards an increase in mortality among people of these age groups. The purpose of this research is to study the features of constructing an algorithm for providing geriatric and gerontological care in the Republic of Kazakhstan, considering the international experience accumulated in this field. The basis of the methodological approach in this study is a combination of a systematic analysis of the accumulated international experience in the field of geriatric and gerontological care, with an analytical study of the actual possibilities of constructing an algorithm for providing assistance based on this international experience. The main results obtained in the course of this study are the definition of the main stages of the algorithm for providing geriatric and gerontological care, and the definition of the main age groups of patients, more than other categories in need of this kind of assistance, formulated on the basis of accumulated international experience in this area. The results of this research work, including the conclusions formulated on their basis, have significant practical significance for disabled elderly people in need of medical care, and for social and medical service workers whose direct professional responsibilities include providing medical care to elderly people.
Talent Incentive Policy of Chinese High-tech Enterprises from the Perspective of Industrial Informatization Intervention
Authors: HUANG Zhangzhong , LIU Yaoping , LI Bijie
Published: March 2024

Priority development of education is the fundamental guarantee for the construction of high-level talent highlands. Technological self-reliance and self-improvement are strategic support for the construction of high-level talent highlands, and talent innovation guidance is the intrinsic driving force for the construction of high-level talent highlands. The construction of a high-level talent highland in the Guangdong Hong Kong Macao Greater Bay Area requires the integration of innovative elements that connect the “education chain, technology chain, and talent chain”. It is necessary to build a three-dimensional integrated spatial architecture of “education technology talent”. We need to build a community that integrates “education highland, technology highland, and talent highland”. Accelerating the construction of high-level talent highlands in the Guangdong Hong Kong Macao Greater Bay Area requires the construction of a highland for scientific and technological innovation talents, a highland for technical and skilled talents, and a highland for scientific and technological finance talents. Based on this, this article selected 399 listed high-tech enterprises in the Greater Bay Area as the research objects, and conducted multiple regression on the relevant data of sample enterprises from the perspective of property rights heterogeneity from 2018 to 2021 to reveal which open innovation model can effectively solve specific situational problems faced by enterprises. The multi role matching mechanism can effectively improve the performance of new product development and its market competitive advantage of enterprises, as well as how the nature of property rights affects the relationship between open innovation strategies and new product development performance of enterprises. The research results show that, firstly, open innovation between enterprises is beneficial for the precise improvement of product development performance by high-level talents in enterprises. Secondly, open innovation in industry, academia, and research is beneficial for improving talent performance in enterprises, but its effect is weaker than that of open innovation between enterprises. Enterprises focus more on the open innovation model between enterprises.
Analisis Faktor Project Based Learning Melalui Grand Teori S-O-R pada Manajemen Pemasaran
Authors: Suryadi  , Samboro Joko , Yunianto Dika Rizky
Published: March 2024

Changes in the Independent Curriculum Free Learning in the Industrial Revolution Era 4.0 is a challenge for changing the learning paradigm, communicating the affective domain in the Gradation of Attitudes, Knowledge and skills that require the concept of Stimulus Organism Response. Implementation of this learning is a continuation of Blended in type discovery and problem base learning (Suryadi, et al 2020) which shows a very effective impact for project tasks according to industry needs. Project based learning is a scientific learning model that emphasizes students to learn to find and discover for themselves an incomplete concept or principle. The research objective is to analyze the dominant factors of the Marketing Management project base learning model. This research method is "Four-D", the sampling technique uses probability sampling techniques and data collection techniques using observation methods, learning (Project Based Learning), pretest & post test methods, and questionnaire methods. Factor analysis data analysis techniques. Findings of social attitudes, motivation and activity as determinants of achievement for which 75 statements in order of importance (1) Social attitudes of 25 questions with a factor loading value of 0.5 to 0.89 (2) Motivation a number of 12 questions with a loading factor value of between 0.60 to 0.80 (3) The activity of a number of 4 question items with a loading factor value between 0.56 to 0.63. Project Based Learning is suitable for vocational.
A review of the current state of natural biomaterials in wound healing applications
Authors: Ansari Mojtaba , Darvishi Ahmad
Published: March 2024

Skin, the largest biological organ, consists of three main parts: the epidermis, dermis, and subcutaneous tissue. Wounds are abnormal wounds in various forms, such as lacerations, burns, chronic wounds, diabetic wounds, acute wounds, and fractures. The wound healing process is dynamic, complex, and lengthy in four stages involving cells, macrophages, and growth factors. Wound dressing refers to a substance that covers the surface of a wound to prevent infection and secondary damage. Biomaterials applied in wound management have advanced significantly. Natural biomaterials are increasingly used due to their advantages including biomimicry of ECM, convenient accessibility, and involvement in native wound healing. However, there are still limitations such as low mechanical properties and expensive extraction methods. Therefore, their combination with synthetic biomaterials and/or adding bioactive agents has become an option for researchers in this field. In the present study, the stages of natural wound healing and the effect of biomaterials on its direction, type, and level will be investigated. Then, different types of polysaccharides and proteins were selected as desirable natural biomaterials, polymers as synthetic biomaterials with variable and suitable properties, and bioactive agents as effective additives. In the following, the structure of selected biomaterials, their extraction and production methods, their participation in wound healing, and quality control techniques of biomaterials-based wound dressings will be discussed.
Optimization of a tunable process for rapid production of calcium phosphate microparticles using a droplet-based microfluidic platform
Authors: Alaoui Selsouli Y. , Rho H. S. , Eischen-Loges M. , Galván-Chacón V. P. , Stähli C. , Viecelli Y. , Döbelin N. , Bohner M. , Tahmasebi Birgani Z. , Habibović P.
Published: March 2024

Calcium phosphate (CaP) biomaterials are amongst the most widely used synthetic bone graft substitutes, owing to their chemical similarities to the mineral part of bone matrix and off-the-shelf availability. However, their ability to regenerate bone in critical-sized bone defects has remained inferior to the gold standard autologous bone. Hence, there is a need for methods that can be employed to efficiently produce CaPs with different properties, enabling the screening and consequent fine-tuning of the properties of CaPs towards effective bone regeneration. To this end, we propose the use of droplet microfluidics for rapid production of a variety of CaP microparticles. Particularly, this study aims to optimize the steps of a droplet microfluidic-based production process, including droplet generation, in-droplet CaP synthesis, purification and sintering, in order to obtain a library of CaP microparticles with fine-tuned properties. The results showed that size-controlled, monodisperse water-in-oil microdroplets containing calcium- and phosphate-rich solutions can be produced using a flow-focusing droplet-generator microfluidic chip. We optimized synthesis protocols based on in-droplet mineralization to obtain a range of CaP microparticles without and with inorganic additives. This was achieved by adjusting synthesis parameters, such as precursor concentration, pH value, and aging time, and applying heat treatment. In addition, our results indicated that the synthesis and fabrication parameters of CaPs in this method can alter the microstructure and the degradation behavior of CaPs. Overall, the results highlight the potential of the droplet microfluidic platform for engineering CaP microparticle biomaterials with fine-tuned properties.
Aberrant stem cell and developmental programs in pediatric leukemia
Authors: Ling Rebecca E. , Cross Joe W. , Roy Anindita
Published: March 2024

Hematopoiesis is a finely orchestrated process, whereby hematopoietic stem cells give rise to all mature blood cells. Crucially, they maintain the ability to self-renew and/or differentiate to replenish downstream progeny. This process starts at an embryonic stage and continues throughout the human lifespan. Blood cancers such as leukemia occur when normal hematopoiesis is disrupted, leading to uncontrolled proliferation and a block in differentiation of progenitors of a particular lineage (myeloid or lymphoid). Although normal stem cell programs are crucial for tissue homeostasis, these can be co-opted in many cancers, including leukemia. Myeloid or lymphoid leukemias often display stem cell-like properties that not only allow proliferation and survival of leukemic blasts but also enable them to escape treatments currently employed to treat patients. In addition, some leukemias, especially in children, have a fetal stem cell profile, which may reflect the developmental origins of the disease. Aberrant fetal stem cell programs necessary for leukemia maintenance are particularly attractive therapeutic targets. Understanding how hijacked stem cell programs lead to aberrant gene expression in place and time, and drive the biology of leukemia, will help us develop the best treatment strategies for patients.
Life cycle assessment of iron-biomass supported catalyst for Fischer Tropsch synthesis
Authors: Amin Muhammad , Shah Hamad Hussain , Naveed Abdul Basit , Iqbal Amjad , Gamil Yaser , Najeh Taoufik
Published: March 2024

The iron-based biomass-supported catalyst has been used for Fischer-Tropsch synthesis (FTS). However, there is no study regarding the life cycle assessment (LCA) of biomass-supported iron catalysts published in the literature. This study discusses a biomass-supported iron catalyst’s LCA for the conversion of syngas into a liquid fuel product. The waste biomass is one of the source of activated carbon (AC), and it has been used as a support for the catalyst. The FTS reactions are carried out in the fixed-bed reactor at low or high temperatures. The use of promoters in the preparation of catalysts usually enhances C5+ production. In this study, the collection of precise data from on-site laboratory conditions is of utmost importance to ensure the credibility and validity of the study’s outcomes. The environmental impact assessment modeling was carried out using the OpenLCA 1.10.3 software. The LCA results reveals that the synthesis process of iron-based biomass supported catalyst yields a total impact score in terms of global warming potential (GWP) of 1.235E + 01 kg CO2 equivalent. Within this process, the AC stage contributes 52% to the overall GWP, while the preparation stage for the catalyst precursor contributes 48%. The comprehensive evaluation of the iron-based biomass supported catalyst’s impact score in terms of human toxicity reveals a total score of 1.98E−02 kg 1,4-dichlorobenzene (1,4-DB) equivalent.
A rare morphology of the cardiac fibroma in a child: a case report
Authors: Tian Yunfei , Lin Jiayi , Yang Xiaohui , Zeng Debin , Hu Yuan , Chen Jingnan , Wu Zhongshi , Deng Xicheng
Published: March 2024

Here we report a rare morphology of a cardiac fibroma in a child. A 2-year and 8-month-old toddler came for “chronic constipation” and was found to have a heart murmur on cardiac auscultation. Further transthoracic echocardiography suggested “a strong echogenic mass in the left ventricular wall, with some part of “a string of beads” in shape extending into left ventricle outflow tract”, which was atypical for either a tumor, thrombus or vegetation. The child underwent resection of the mass and mitral valvuloplasty. Pathological examination confirmed the mass as a cardiac fibroma.
Effects of irrigation dams on riverine biota in mountain streams
Authors: Rocha Pompeu Cássia , Peñas Francisco J. , Barquín José
Published: March 2024

Mountain streams harbor unique biodiversity and provide essential ecosystem services to human societies. Yet, these ecosystems face numerous threats, such as the construction of dams and land use changes, leading to rapid habitat degradation, water pollution, and biodiversity loss. In this study, we assess the effect of irrigation dams on mountain riverine biota using traditional biotic indices and trait-based approaches. We selected diatom and macroinvertebrate communities surveyed between 2015 and 2017 in mountain streams located in different regions in northern Spain (Cantabrian Cordillera, Iberian System, and Pyrenees) under natural and altered flow conditions (i.e., downstream of irrigation dams). Hydrological and biological changes related to the presence of dams, the mountain range, and the interaction between these two factors were identified. Summer flows, frequency of high flow events, and minimum annual flows timing were significantly affected by irrigation dams, independently of the region. Winter flows, the magnitude of high flow extremes, and the number of flow rises and falls varied significantly with the dam-mountain range interaction. The frequency and duration of flow pulses depended on the mountain range only. In the Cantabrian Cordillera, a region with larger reservoirs (>150 hm3), impacted sites showed a marked inversion of the seasonal flow patterns (i.e., increased summer flows but reduced winter flows). In the other mountain ranges, reservoirs had smaller storage volumes and multiple purposes, causing significant flow change frequency variations. Diatom traits, taxonomic richness, diversity, and IPS score varied with dam presence and mountain ranges, while macroinvertebrate traits and biotic indices responded weakly. These findings suggest that diatom communities might be more sensitive to hydrological alteration, while macroinvertebrates might be more influenced by space-related factors, such as biogeography and dispersal, overriding dam-related impacts. Furthermore, dam-related changes in ecosystems may depend not only on the presence of dams and their characteristics (e.g., reservoir size and operation), but also on local conditions and biogeography. Our findings emphasize that, when using pre-existing biomonitoring datasets, although some dam-related patterns emerge (e.g., with diatoms), other patterns may be constrained by the datasets’ low spatio-temporal coverage and taxonomic resolution, highlighting the need of well-structured study designs.
The genetic architecture of complete blood counts in lactating Holstein dairy cows
Authors: Siberski-Cooper Cori J. , Mayes Mary S. , Gorden Patrick J. , Kramer Luke , Bhatia Vishesh , Koltes James E.
Published: March 2024

Complete blood counts (CBCs) measure the abundance of individual immune cells, red blood cells, and related measures such as platelets in circulating blood. These measures can indicate the health status of an animal; thus, baseline circulating levels in a healthy animal may be related to the productive life, resilience, and production efficiency of cattle. The objective of this study is to determine the heritability of CBC traits and identify genomic regions that are associated with CBC measurements in lactating Holstein dairy cattle. The heritability of CBCs was estimated using a Bayes C0 model. The study population consisted of 388 cows with genotypes at roughly 75,000 markers and 16 different CBC phenotypes taken at one to three time points (n = 33, 131, and 224 for 1, 2, and 3 time points, respectively). Heritabilities ranged from 0.00 ± 0.00 (red cell distribution width) to 0.68 ± 0.06 (lymphocytes). A total of 96 different 1-Mb windows were identified that explained more than 1% of the genetic variance for at least one CBC trait, with 10 windows explaining more than 1% of the genetic variance for two or more traits. Multiple genes in the identified regions have functions related to immune response, cell differentiation, anemia, and disease. Positional candidate genes include RAD52 motif-containing protein 1 (RDM1), which is correlated with the degree of immune infiltration of immune cells, and C-X-C motif chemokine ligand 12 (CXCL12), which is critically involved in neutrophil bone marrow storage and release regulation and enhances neutrophil migration. Since animal health directly impacts feed intake, understanding the genetics of CBCs may be useful in identifying more disease-resilient and feed-efficient dairy cattle. Identification of genes responsible for variation in CBCs will also help identify the variability in how dairy cattle defend against illness and injury.
The effects of Pediococcus acidilactici MA18/5M on growth performance, gut integrity, and immune response using in vitro and in vivo Pacific salmonid models
Authors: Soto-Dávila Manuel , Langlois Fiorotto Luana , Heath John W. , Lumsden John S. , Reid Gregor , Dixon Brian
Published: March 2024

Microbial management is central to aquaculture’s efficiency. Pediococcus acidilactici MA18/5M has shown promising results promoting growth, modulation of the immune response, and disease resistance in many fishes. However, the mechanisms through which this strain confers health benefits in fish are poorly understood, particularly in Pacific salmonid models. Briefly, the aims of this study were to i) assess the protective effects of P. acidilactici MA18/5M by examining gut barrier function and the expression of tight junction (TJ) and immune genes in vitro and in vivo, and ii) to determine the protective effects of this strain against a common saltwater pathogen, Vibrio anguillarum J382. An in vitro model of the salmonid gut was employed utilizing the cell line RTgutGC. Barrier formation and integrity assessed by TEER measurements in RTgutGC, showed a significant decrease in resistance in cells exposed only to V. anguillarum J382 for 24 h, but pre-treatment with P. acidilactici MA18/5M for 48 h mitigated these effects. While P. acidilactici MA18/5M did not significantly upregulate tight junction and immune molecules, pre-treatment with this strain protected against pathogen-induced insults to the gut barrier. In particular, the expression of ocldn was significantly induced by V. anguillarum J382, suggesting that this molecule might play a role in the host response against this pathogen. To corroborate these observations in live fish, the effects of P. acidilactici MA18/5M was evaluated in Chinook salmon reared in real aquaculture conditions. Supplementation with P. acidilactici MA18/5M had no effect on Chinook salmon growth parameters after 10 weeks. Interestingly, histopathological results did not show alterations associated with P. acidilactici MA18/5M supplementation, indicating that this strain is safe to be used in the industry. Finally, the expression pattern of transcripts encoding TJ and immune genes in all the treatments suggest that variation in expression is more likely to be due to developmental processes rather than P. acidilactici MA18/5M supplementation. Overall, our results showed that P. acidilactici MA18/5M is a safe strain for use in fish production, however, to assess the effects on growth and immune response previously observed in other salmonid species, an assessment in adult fish is needed.
Construction and validation of a machine learning-based nomogram to predict the prognosis of HBV associated hepatocellular carcinoma patients with high levels of hepatitis B surface antigen in primary local treatment: a multicenter study
Authors: Xiong Yiqi , Qiao Wenying , Wang Qi , Li Kang , Jin Ronghua , Zhang Yonghong
Published: March 2024

Background

Hepatitis B surface antigen (HBsAg) clearance is associated with improved long-term outcomes and reduced risk of complications. The aim of our study was to identify the effects of levels of HBsAg in HCC patients undergoing TACE and sequential ablation. In addition, we created a nomogram to predict the prognosis of HCC patients with high levels of HBsAg (≥1000U/L) after local treatment.

Method

This study retrospectively evaluated 1008 HBV-HCC patients who underwent TACE combined with ablation at Beijing Youan Hospital and Beijing Ditan Hospital from January 2014 to December 2021, including 334 patients with low HBsAg levels and 674 patients with high HBsAg levels. The high HBsAg group was divided into the training cohort (N=385), internal validation cohort (N=168), and external validation cohort (N=121). The clinical and pathological features of patients were collected, and independent risk factors were identified using Lasso-Cox regression analysis for developing a nomogram. The performance of the nomogram was evaluated by C-index, receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) curves in the training and validation cohorts. Patients were classified into high-risk and low-risk groups based on the risk scores of the nomogram.

Result

After PSM, mRFS was 28.4 months (22.1-34.7 months) and 21.9 months (18.5-25.4 months) in the low HBsAg level and high HBsAg level groups (P<0.001). The content of the nomogram includes age, BCLC stage, tumor size, globulin, GGT, and bile acids. The C-index (0.682, 0.666, and 0.740) and 1-, 3-, and 5-year AUCs of the training, internal validation, and external validation cohorts proved good discrimination of the nomogram. Calibration curves and DCA curves suggested accuracy and net clinical benefit rates. The nomogram enabled to classification of patients with high HBsAg levels into low-risk and high-risk groups according to the risk of recurrence. There was a statistically significant difference in RFS between the two groups in the training, internal validation, and external validation cohorts (P<0.001).

Conclusion

High levels of HBsAg were associated with tumor progression. The nomogram developed and validated in the study had good predictive ability for patients with high HBsAg levels.
Cooperative interaction of interferon regulatory factor -1 and bromodomain—containing protein 4 on RNA polymerase activation for intrinsic innate immunity
Authors: Xu Xiaofang , Qiao Dianhua , Brasier Allan R.
Published: March 2024

Introduction

The human orthopneumovirus, Respiratory Syncytial Virus (RSV), is the causative agent of severe lower respiratory tract infections (LRTI) and exacerbations of chronic lung diseases. In immune competent hosts, RSV productively infects highly differentiated epithelial cells, where it elicits robust anti-viral, cytokine and remodeling programs. By contrast, basal cells are relatively resistant to RSV infection, in part, because of constitutive expression of an intrinsic innate immune response (IIR) consisting of a subgroup of interferon (IFN) responsive genes. The mechanisms controlling the intrinsic IIR are not known.

Methods

Here, we use human small airway epithelial cell hSAECs as a multipotent airway stem cell model to examine regulatory control of an intrinsic IIR pathway.

Results

We find hSAECs express patterns of intrinsic IIRs, highly conserved with pluri- and multi-potent stem cells. We demonstrate a core intrinsic IIR network consisting of Bone Marrow Stromal Cell Antigen 2 (Bst2), Interferon Induced Transmembrane Protein 1 (IFITM1) and Toll-like receptor (TLR3) expression are directly under IRF1 control. Moreover, expression of this intrinsic core is rate-limited by ambient IRF1• phospho-Ser 2 CTD RNA Polymerase II (pSer2 Pol II) complexes binding to their proximal promoters. In response to RSV infection, the abundance of IRF1 and pSer2 Pol II binding is dramatically increased, with IRF1 complexing to the BRD4 chromatin remodeling complex (CRC). Using chromatin immunoprecipitation in IRF1 KD cells, we find that the binding of BRD4 is IRF1 independent. Using a small molecule inhibitor of the BRD4 acetyl lysine binding bromodomain (BRD4i), we further find that BRD4 bromodomain interactions are required for stable BRD4 promoter binding to the intrinsic IIR core promoters, as well as for RSV-inducible pSer2 Pol II recruitment. Surprisingly, BRD4i does not disrupt IRF1-BRD4 interactions, but disrupts both RSV-induced BRD4 and IRF1 interactions with pSer2 Pol II.

Conclusions

We conclude that the IRF1 functions in two modes- in absence of infection, ambient IRF1 mediates constitutive expression of the intrinsic IIR, whereas in response to RSV infection, the BRD4 CRC independently activates pSer2 Pol II to mediates robust expression of the intrinsic IIR. These data provide insight into molecular control of anti-viral defenses of airway basal cells.
Clinicopathologic analysis of nodal T-follicular helper cell lymphomas, a multicenter retrospective study from China
Authors: Ma Shanshan , Li Suxiao , Zuo Xiaona , Li Wencai , Wang Lifu , Liu Weiping , Wang Zhe , Sang Wei , Wang Yanjie , Zhang Xudong , Zhang Mingzhi
Published: March 2024

Background

Nodal T-follicular helper cell lymphomas (nTFHLs) represent a new family of peripheral T-cell lymphomas (PTCLs), and comparative studies of their constituents are rare.

Methods

This study retrospectively enrolled 10 patients with nTFHL-F and 30 patients with nTFHL-NOS diagnosed between December 2017 and October 2023 at six large comprehensive tertiary hospitals; 188 patients with nTFHL-AI were diagnosed during the same period at the First Affiliated Hospital of Zhengzhou University for comparison.

Results

Compared with nTFHL-AI, nTFHL-NOS patients exhibited better clinical manifestations, lower TFH expression levels, and a lower Ki-67 index. However, no differences in clinicopathological features were observed between nTFHL-F and nTFHL-AI patients as well as nTFHL-NOS patients. According to the survival analysis, the median OS for patients with nTFHL-NOS, nTFHL-AI, and nTFHL-F were 14.2 months, 10 months, and 5 months, respectively, whereas the median TTP were 14 months, 5 months, and 3 months, respectively. Statistical analysis revealed differences in TTP among the three subtypes(P=0.0173). Among the population of patients receiving CHOP-like induction therapy, there were significant differences in the OS and TTP among the nTFHL-NOS, nTFHL-AI, and nTFHL-F patients (P=0.0134, P=0.0205). Both the GDPT and C-PET regimens significantly improved the ORR, OS, and PFS in nTFHL patients.

Conclusion

There are significant differences in the clinical manifestations, pathology, and survival outcomes among the three subtypes of nTFHLs. However, further research with a larger sample size, and involving clinical pathology and molecular genetics is needed to determine the distinctive biological characteristics of these tumors.
Choosing T-cell sources determines CAR-T cell activity in neuroblastoma
Authors: García-García Lorena , G. Sánchez Elena , Ivanova Mariya , Pastora Keren , Alcántara-Sánchez Cristina , García-Martínez Jorge , Martín-Antonio Beatriz , Ramírez Manuel , González-Murillo África
Published: March 2024

Introduction

The clinical success of chimeric antigen receptor-modified T cells (CAR-T cells) for hematological malignancies has not been reproduced for solid tumors, partly due to the lack of cancer-type specific antigens. In this work, we used a novel combinatorial approach consisting of a versatile anti-FITC CAR-T effector cells plus an FITC-conjugated neuroblastoma (NB)-targeting linker, an FITC-conjugated monoclonal antibody (Dinutuximab) that recognizes GD2.

Methods

We compared cord blood (CB), and CD45RA-enriched peripheral blood leukapheresis product (45RA) as allogeneic sources of T cells, using peripheral blood (PB) as a control to choose the best condition for anti-FITC CAR-T production. Cells were manufactured under two cytokine conditions (IL-2 versus IL-7+IL-15+IL-21) with or without CD3/CD28 stimulation. Immune phenotype, vector copy number, and genomic integrity of the final products were determined for cell characterization and quality control assessment. Functionality and antitumor capacity of CB/45RA-derived anti-FITC CAR-T cells were analyzed in co-culture with different anti-GD2-FITC labeled NB cell lines.

Results

The IL-7+IL-15+IL-21 cocktail, in addition to co-stimulation signals, resulted in a favorable cell proliferation rate and maintained less differentiated immune phenotypes in both CB and 45RA T cells. Therefore, it was used for CAR-T cell manufacturing and further characterization. CB and CD45RA-derived anti-FITC CAR-T cells cultured with IL-7+IL-15+IL-21 retained a predominantly naïve phenotype compared with controls. In the presence of the NB-FITC targeting, CD4+ CB-derived anti-FITC CAR-T cells showed the highest values of co-stimulatory receptors OX40 and 4-1BB, and CD8+ CAR-T cells exhibited high levels of PD-1 and 4-1BB and low levels of TIM3 and OX40, compared with CAR-T cells form the other sources studied. CB-derived anti-FITC CAR-T cells released the highest amounts of cytokines (IFN-γ and TNF-α) into co-culture supernatants. The viability of NB target cells decreased to 30% when co-cultured with CB-derived CAR-T cells during 48h.

Conclusion

CB and 45RA-derived T cells may be used as allogeneic sources of T cells to produce CAR-T cells. Moreover, ex vivo culture with IL-7+IL-15+IL-21 could favor CAR-T products with a longer persistence in the host. Our strategy may complement the current use of Dinutuximab in treating NB through its combination with a targeted CAR-T cell approach.
Modular design of bi- and multi-specific knob domain fusions
Authors: Kuravsky Mikhail , Gibbons Glyn F. , Joyce Callum , Scott-Tucker Anthony , Macpherson Alex , Lawson Alastair D. G.
Published: March 2024

Introduction

The therapeutic potential of bispecific antibodies is becoming widely recognised, with over a hundred formats already described. For many applications, enhanced tissue penetration is sought, so bispecifics with low molecular weight may offer a route to enhanced potency. Here we report the design of bi- and tri-specific antibody-based constructs with molecular weights as low as 14.5 and 22 kDa respectively.

Methods

Autonomous bovine ultra-long CDR H3 (knob domain peptide) modules have been engineered with artificial coiled-coil stalks derived from Sin Nombre orthohantavirus nucleocapsid protein and human Beclin-1, and joined in series to produce bi- and tri-specific antibody-based constructs with exceptionally low molecular weights.

Results

Knob domain peptides with coiled-coil stalks retain high, independent antigen binding affinity, exhibit exceptional levels of thermal stability, and can be readily joined head-to-tail yielding the smallest described multi-specific antibody format. The resulting constructs are able to bind simultaneously to all their targets with no interference.

Discussion

Compared to existing bispecific formats, the reduced molecular weight of the knob domain fusions may enable enhanced tissue penetration and facilitate binding to cryptic epitopes that are inaccessible to conventional antibodies. Furthermore, they can be easily produced at high yield as recombinant products and are free from the heavy-light chain mispairing issue. Taken together, our approach offers an efficient route to modular construction of minimalistic bi- and multi-specifics, thereby further broadening the therapeutic scope for knob domain peptides.
Simultaneous determination of seawater trimethylamine and methanol by purge and trap gas chromatography using dual nitrogen-phosphorus detector and flame-ionization detector
Authors: Jiang Fei , Zhou Zhen , Wang Jin-Yan , Guan Wen-Jia , Han Lei-Gang , Lin Xian-Biao , Zhuang Guang-Chao
Published: March 2024

Compounds containing one carbon atom or no carbon-carbon bond (C1 compounds), such as trimethylamine and methanol, are important climate relevant gases in the atmosphere and play key roles in global warming. The ocean is a significant source or sink of such compounds, while the concentrations of trimethylamine and methanol in seawater remain largely unconstrained due to the analytical challenges involved. Therefore, it is necessary to establish a continuous, rapid and sensitive method for the determination of these compounds with high polarity, volatility or solubility at low seawater concentrations. Here we developed a purge and trap system, coupled to a gas chromatography equipped with dual nitrogen phosphorus detector (NPD) and flame ionization detector (FID) for the simultaneous online analysis of trimethylamine and methanol at nanomolar range using a small sample volume (~ 10 mL). The dual detection of trimethylamine and methanol with NPD or FID was achieved by installing a capillary flow splitter between the capillary column and detectors. After modification and optimization of the setup and conditions, excellent linearity (R2 > 0.99) and repeatability (< 6%) were obtained for both compounds; the detection limits for trimethylamine and methanol were 0.3 nM and 17.6 nM, respectively. Using this method, water samples collected from coastal and open ocean were analyzed; trimethylamine and methanol concentrations ranged from 0.6 to 18.8 nM and 26.0 to 256.2 nM, respectively. Collectively, this method allowed for online, rapid, sensitive and simultaneous quantification of trace trimethylamine and methanol concentrations with low-cost instrumentation and small sample volume, which makes it promising for further application in volatile compounds analysis in marine environments.