bluuebunny/crossref_metadata_2025 huggingface dataset:
Respon Tanaman dan Produksi Tanaman Jagung Pulut terhadap Dosis Pupuk NPK dan Waktu Pembumbunan
Authors: Jumiatun  , Nur Indriawati Ika , Dyah Utami Christa , Muhklisin Ilham
Published: August 2023

Jagung pulut dapat digunakan sebagai bahan pangan alternatif pengganti beras dalam upaya diversifikasi pangan. Akan tetapi produksi dan minat masyarakat yang masih rendah dibutuhkan upaya untuk meningkatkan produksi jagung pulut. Salah satu upaya yang dapat dilakukan untuk meningkatkan produksi jagung pulut adalah dengan perbaikan teknik budidaya seperti pemupukan dan pembumbunan.Tujuan penelitian ini yaitu untuk mengkaji pengaruh dosis pupuk NPK dan waktu pembumbunan  terhadap pertumbuhan dan produksi tanaman jagung pulut. Rancangan penelitian yang digunakan dalam penelitian ini adalah Rancangan Acak Kelompok Faktorial (RAKF) yang terdiri dari 2 faktor. Faktor pertama adalah dosis pupuk NPK yang terdapat lima taraf yaitu 100 kg/ha, 150 kg/ha, 200 kg/ha, 250 kg/ha, dan 300 kg/ha. Sedangkan faktor kedua adalah waktu pembumbunan yang terdiri dari dua taraf yaitu pembumbunan 2 kali (14 HST dan 21 HST) dan pembumbunan 3 kali (14 HST, 21 HST dan 28 HST). Hasil penelitian menunjukkan bahwa perlakuan waktu pembumbunan dan dosis pupuk NPK memberikan pengaruh yang tidak nyata pada semua variabel pengataman. Hasil rata-rata produksi jagung pulut dengan pemberian pupuk NPK dan pembumbunan mendapatkan rerata hasil sebesar 16 ton/ha.
Phytoplankton transport out of the euphotic zone by frontal subduction and gravitational sinking in the Santa Barbara Channel, CA, USA
Authors: Washburn L , Brzezinski MA , Gotschalk C , Mylonakis K , Garcia-Cervera C , Kui L
Published: August 2023

Production of particulate organic carbon (POC) in nutrient-rich coastal waters over continental shelves, its export to depth, and its transport to deeper ocean waters is a poorly quantified component of the global carbon cycle. A critical step in quantifying this vertical transport is identifying shelf processes that export phytoplankton out of the euphotic zone. During cruises of the Santa Barbara Coastal Long Term Ecological Research project, we discovered substantial chlorophyll a (chl a) below the euphotic zone in the Santa Barbara Channel, a part of the southern California Current System. Observations from towed, undulating vehicles revealed deep chlorophyll layers near fronts where upwelled waters from central California converged with lower-density waters from the Southern California Bight. The mean fraction ± 1 standard deviation (SD) of chlorophyll biomass below the euphotic zone spanning the entire Santa Barbara Channel was ~7 ± 9% during 13 cruises averaged across all seasons. In one spring cruise, the fraction was ~30%, and in other cruises the layers were absent. Phytoplankton export out of the euphotic zone by subduction was indicated by spatial coherence between chl a and sloping density surfaces. Vertical plumes of chl a crossing density surfaces indicated enhanced gravitational export within cyclonic eddies. Chl a in water samples below the euphotic zone, away from fronts and cyclonic flows, suggested additional phytoplankton export. Our results emphasize the importance of subduction in the export of phytoplankton and POC out of the euphotic zone in coastal upwelling systems.
İlköğretim Matematik Öğretmen Adaylarının Yaratıcı Drama ile Öğrenme Kuramlarını Çevrimiçi Deneyimlemesi
Authors: BAĞ Gamze , ARIK KARAMIK Gözdegül
Published: August 2023

Öğrenme kuramları, “öğrenmenin nasıl gerçekleşeceğini” açıklayan farklı soyut bilgiler barındırabilmektedir. Bu soyut bilgilerin soyut bir disiplin olan matematikle çevrimiçi deneyimlenmesi ise hem öğretmen hem de öğretmen adayları için zor olabilmektedir. Bu amaçla matematik dersi için önemli olduğu düşünülen yapılandırmacı yaklaşım, sosyo-kültürel teori, APOS teori ve sezgisel kural teorisini, öğrenenlerin yaratıcı drama ile çevrimiçi deneyimlemesi önem arz etmektedir. Bu bağlamdan hareketle bu çalışmada “İlköğretim matematik öğretmen adaylarının öğrenme kuramlarını yaratıcı drama ile çevrimiçi deneyimlemesi nasıldır?” sorusuna cevap aranmaktadır. Nitel araştırma yöntemlerinden durum (örnek olay) çalışması benimsenmiştir. Araştırmanın katılımcılarını bir devlet üniversitesinin ilköğretim matematik öğretmenliği anabilim dalında öğrenim gören 21 katılımcı oluşturmuş olup katılımcılar amaçlı örneklem yöntemi ile seçilmiştir. Veriler, yarı yapılandırılmış formlar ve atölye değerlendirme formları ile toplanmıştır. Katılımcılardan e-posta ile toplanan veriler içerik analizi yardımıyla analiz edilmiştir. Araştırmanın bulguları öğretmen adaylarının yapılandırmacı yaklaşım, sosyo-kültürel teori, APOS teori ve sezgisel kural teorisine ait çevrimiçi deneyimlemelerinin matematiğe, dramaya ve kurama yönelik olmak üzere üç tema altında toplandığını göstermektedir. Ayrıca çalışmada, öğretmen adaylarının öğrenme kuramlarını matematik dersinde drama yardımı ile kullanabileceklerine olan fikirlerinin arttığı yönündeki bulgular da yer almaktadır.
Ortaokul 7. Sınıf Öğrencilerinin Tam Sayılar ve Rasyonel Sayılarda Problem Çözme Süreçlerinin Newman’ın Hata Analizi Adımlarına Göre İncelenmesi
Authors: ERDOĞAN Rüveyda , ÖZKAYA Ali
Published: August 2023

Bu araştırma 7. sınıf öğrencilerinin sözel matematik problemlerini çözerken yaptıkları hataları Newman’ın hata analizi adımlarına göre inceleyerek hataların kaynaklarını tespit etmek amacıyla yapılmıştır. Araştırmaya 2021-2022 eğitim-öğretim yılında Akdeniz Bölgesindeki bir devlet ortaokulunda 7. sınıfta öğrenim gören 60 öğrenci katılmıştır. Çalışma nitel olarak tasarlanmış olup veriler betimsel analiz yöntemiyle analiz edilmiştir. Öğrencilerden elde edilen cevaplar Newman Hata Analiz Envanteri ile incelenmiştir. Bu öğrenciler içinden en çok hata yapan 10 öğrenci ile de bireysel görüşme yapılmıştır. Araştırmanın sonucunda katılımcıların en çok sırasıyla anlama basamağında, süreç becerilerinde ve dönüşüm basamağında hata yaptığı tespit edilmiştir. Çalışma sonuçlarına göre matematik derslerinde problem çözme stratejileri üzerine daha fazla odaklanılması, öğretmenlerin, problem çözme sürecinde öğrencilerin yaptıkları hataları analiz ederek öğrencilere dönüt vermeleri önerilir. Yapılan öğrenci hatalarının en çok anlama basamağında olması nedeniyle hem okuduğunu anlama hem de matematiksel okuryazarlık üzerinde durularak matematik ve Türkçe öğretmenleri arasındaki iş birliği güçlendirilmelidir.
İdeal Bir Okul Öncesi Eğitim Ortamı: Ebeveynlerin Okul Öncesi Eğitim Kurumlarından Beklentileri
Authors: BULDU Metehan , GÜNER PEKACAR Rumeysa
Published: August 2023

Ebeveynlerin bakış açıları, okullar ve eğitimciler için önemli bir geri bildirim kaynağıdır. Ebeveynlerin öğrenme ortamı hakkındaki görüşlerini araştırmak, güçlü yönlerini ve iyileştirilmesi gereken alanları belirlemeye yardımcı olmaktadır. Bu sayede, eğitim ortamının, öğrencilerin ve ebeveynlerin ihtiyaçlarını daha iyi karşılamak adına, fiziksel ve eğitsel ortamın sürekli olarak uyarlanması ve iyileştirmesi mümkün olacaktır. Bu amaçla, Ankara ilinde (merkez ilçeler) yer alan 26 ebeveyne kolay ulaşılabilir örneklem yöntemi ile ulaşılmış ve yarı-yapılandırılmış görüşmeler ile çalışma verileri toplanmıştır. Görüşmeler esnasında ebeveynlerin kendi algılarına göre fiziksel (materyal, sınıf büyüklüğü, öğrenci sayısı, maddi beklenti) ve eğitsel (gelişim alanlarını destekleme, okulla iletişim, ) açılardan ideal bir okul ortamından beklentilerinin neler olduğu sorulmuştur. Görüşmeler sonrasında elde edilen bulgular tematik analiz yöntemin ile analiz edilmiştir. Analiz sonucunda, ebeveynlerin verdiği cevaplardan yola çıkarak (1) fiziki beklentiler ve (2) eğitim-öğretim açısından beklentiler olarak iki ana tema geliştirilmiştir. Araştırmanın bulgularında ebeveynlerin yeterli materyal ve ödenen ücret konusunda farklı düzeylerde beklentilerin olduğunu göstermiştir. Özellikle çocukları özel kurumlarda eğitim gören ebeveynler, okullarda materyallerin yetersiz olduğunu ve ödenen paraların devlet okullarına kıyasla çok fazla olduğunu ifade etmişlerdir. Diğer taraftan, ebeveynlerin eğitim öğretim açısından beklentilerinin en çok çocukların öz-bakım (öğrendiklerinin evde de gözlenmesi) ve sosyal (diğer çocuklarla paylaşım, iletişim) gelişim alanlarında olduğunu göstermektedir. Araştırma bulgularına dayanarak, okulların kendi koşullarına dair ebeveynlere fiziksel ve eğitsel açıdan bilgilendirme seminerleri vermeleri, dönem başlarında ebeveynlerin eğitim ortamına dair beklentilerini belirlemeye yönelik düzenli görüşmelerin yapılması ve ev-okul arasındaki bağı güçlü tutmak amacıyla teknolojik imkânların işe koşularak, düzenli iletişim bağı kurmaları önerilmektedir
Özel Eğitim ve Rehabilitasyon Merkezlerinde Çalışan Öğretmenlerin İş Memnuniyetlerinin Belirlenmesi
Authors: İNCE Mehmet , KARABULUT Havva Aysun
Published: August 2023

Bu araştırmanın amacı özel eğitim ve rehabilitasyon merkezlerinde görev yapan öğretmenlerin iş memnuniyetlerinin belirlenmesidir. Bu amaç doğrultusunda nitel araştırma yöntemi desenlerinden betimleyici durum çalışması olarak desenlesen araştırma özel eğitim ve rehabilitasyon merkezinde görev yapan 21 öğretmenle gerçekleştirilmiştir. Araştırmanın verileri yarı yapılandırılmış görüşme formu ve yansıtmalı araştırmacı günlüğü yoluyla toplanmıştır. Elde edilen veriler içerik analiziyle analiz edilerek kodlar, kategoriler ve temalar çıkarılarak yorumlanmıştır. Yapılan analiz sonucunda öğretmenlerin görüşleri, eğitim süreci, sektörel sorunlar ve özel özel eğitim kurumları şeklinde üç tema, yedi kategori ve 21 kod altında toplanmıştır. Her kategoriye ilişkin doğrudan alıntılarla yoluyla her bulgular desteklenmiştir. Araştırma sonunda elde edilen bulgular ilgili literatürle ilişkilendirilerek tartışılmış ve son olarak önerilere yer verilmiştir.
Sosyal Bilgiler Öğretim Programına İlişkin Sosyal Bilgiler Alan Eğitimcilerinin Görüşleri: Bir Q Metot Analizi
Authors: ÇAKMAK Zafer , KAÇAR Turan , AKGÜN İsmail Hakan
Published: August 2023

Sosyal bilgiler dersinin yürütülmesine ilişkin öğretmenlere rehberlik yapan Sosyal Bilgiler Öğretim Programı, 2018-2019 eğitim-öğretim yılında güncellenerek Türkiye’de uygulamaya geçmiştir. Bu açıdan bu çalışmanın amacı Sosyal Bilgiler Öğretim Programına ilişkin sosyal bilgiler alan eğitimcilerinin görüşlerini belirlemektir. Bu çalışma iç içe geçmiş karma desen araştırma yöntemiyle gerçekleştirilmiştir. Bu araştırmanın çalışma grubu 2021-2022 akademik yılında Türkiye’deki devlet üniversitelerinde görevli 30 sosyal bilgiler alan eğitimcisinden oluşmaktadır. Araştırmanın veri toplama aracı araştırmacıların literatür ve alan uzmanlarının önerileri doğrultusunda geliştirdiği Q metot formudur. Bu araştırmanın nicel verileri PQMethod 2.35 istatistik programı ile nitel verileri ise betimsel içerik analizi yöntemiyle analiz edilmiştir. Yapılan analizler doğrultusunda Sosyal Bilgiler Öğretim Programına yönelik katılımcıların görüşlerinin önemli ölçüde benzerlik gösterdiği ve cinsiyet değişkeninin anlamlı bir farklılık oluşturmadığı tespit edilmiştir. Ayrıca Sosyal Bilgiler Öğretim Programının amaç, beceri, öğrenme alanı ve değer boyutlarında yeterli olduğu ancak felsefe, rehberlik, bireysel farklılık ve içerik boyutlarında ise yetersiz olduğu belirlenmiştir.
The “Securitisation” of Muslims in India: Anti-Minority Violence as Governance
Authors: Kaiser Nidah
Published: August 2023

This paper argues that the present observed increase, and shift in the nature, of “communal” violence in Modi’s India, marks a sharp departure from the past, with the crucial difference being the transformation of anti-Muslim violence from a “modality of politics” to a “modality of governance” under the BJP. This paper, thus, proposes the framework of “securitisation” of Muslims, replacing the “communal” violence to understand anti-Muslim violence. This study is based on the legal and case analyses of The Uttar Pradesh Prohibition of Unlawful Conversion of Religion Act, 2021 in seven cases of alleged forced inter-religious conversion. Ethnographic fieldwork was conducted during 2021–2022 across six districts in Uttar Pradesh: Kanpur, Allahabad, Mau, Lucknow, Bareilly and Shahjahanpur. Using these case studies, the paper theorises the coexistence between the democratic governance – the “politics of life” – and securitisation – the “politics of death.”
Simulating the effect of perennialized cropping systems on nitrate-N losses using the SWAT model
Authors: Wilson Grace L. , Mulla David J. , Jordan Nicholas R. , Jungers Jacob M. , Gordon Brad A.
Published: August 2023

Several newly released crop varieties, including the perennial intermediate wheatgrass (grain marketed as Kernza®), and the winter hardy oilseed crop camelina, have been developed to provide both economic return for farmers and reduced nutrient losses from agricultural fields. Though studies have indicated that these crops could reduce nitrate-nitrogen (N) leaching, little research has been done to determine their effectiveness in reducing nitrate-N loading to surface waters at a watershed scale, or in comparing their performance to more traditional perennial crops, such as alfalfa. In this study, nitrate-N losses were predicted using the Soil and Water Assessment Tool (SWAT) model for the Rogers Creek watershed located in south-central Minnesota, USA. Predicted looses of nitrate-N under three perennialized cropping systems were compared to losses given current cropping practices in a corn (Zea mays L.)-soybean (Glycine max L. Merr.) rotation. The perennialized systems included three separate crop rotations: intermediate wheatgrass (IWG) in rotation with soybean, alfalfa in rotation with corn, and winter camelina in rotation with soybean and winter rye. Model simulation of these rotations required creation of new crop files for IWG and winter camelina within SWAT. These new crop files were validated using measured yield, biomass, and nitrate-N data. Model results show that the IWG and alfalfa rotations were particularly effective at reducing nutrient and sediment losses from agricultural areas in the watershed, but smaller reductions were also achieved with the winter camelina rotation. From model predictions, achieving regional water-quality goals of a 30% reduction in nitrate-N load from fields in the watershed required converting approximately 25, 34, or 57% of current corn-soybean area to the alfalfa, IWG, or camelina rotations, respectively. Results of this study indicate that adoption of these crops could achieve regional water quality goals.
3D printed hybrid scaffolds for bone regeneration using calcium methoxyethoxide as a calcium source
Authors: Heyraud Agathe , Tallia Francesca , Sory David , Ting Hung-Kai , Tchorzewska Anna , Liu Jingwen , Pilsworth Hannah L. , Lee Peter D. , Hanna John V. , Rankin Sara M. , Jones Julian R.
Published: August 2023

Introduction: Hybrids consist of inorganic and organic co-networks that are indistinguishable above the nanoscale, which can lead to unprecedented combinations of properties, such as high toughness and controlled degradation.

Methods: We present 3D printed bioactive hybrid scaffolds for bone regeneration, produced by incorporating calcium into our “Bouncy Bioglass”, using calcium methoxyethoxide (CME) as the calcium precursor. SiO2-CaOCME/PTHF/PCL-diCOOH hybrid “inks” for additive manufacturing (Direct Ink Writing) were optimised for synergy of mechanical properties and open interconnected pore channels.

Results and Discussion: Adding calcium improved printability. Changing calcium content (5, 10, 20, 30, and 40 mol.%) of the SiO2-CaOCME/PTHF/PCL-diCOOH hybrids affected printability and mechanical properties of the lattice-like scaffolds. Hybrids containing 30 mol.% calcium in the inorganic network (70S30CCME-CL) printed with 500 µm channels and 100 µm strut size achieved the highest strength (0.90 ± 0.23 MPa) and modulus of toughness (0.22 ± 0.04 MPa). These values were higher than Ca-free SiO2/PTHF/PCL-diCOOH hybrids (0.36 ± 0.14 MPa strength and 0.06 ± 0.01 MPa toughness modulus). Over a period of 90 days of immersion in simulated body fluid (SBF), the 70S30CCME-CL hybrids also kept a stable strain to failure (~30 %) and formed hydroxycarbonate apatite within three days. The extracts released by the 70S30CCME-CL hybrids in growth medium did not cause cytotoxic effects on human bone marrow stromal cells over 24 h of culture.
Insight into biological activities of chemically characterized extract from Marrubium vulgare L. in vitro, in vivo and in silico approaches
Authors: Gourich Aman Allah , Touijer Hanane , Drioiche Aziz , Asbabou Ayoub , Remok Firdaous , Saidi Soukaina , Siddique Farhan , Ailli Atika , Bourhia Mohammed , Salamatullah Ahmad Mohammad , Ouahmane Lahcen , Mouradi Aicha , Eto Bruno , Zair Touriya
Published: August 2023

Aqueous extracts of Marrubium vulgare L. (M. vulgare) are widely used in traditional medicine for their therapeutic effects. Hence, this study aims to evaluate in vitro, in vivo, and in silico the biological activities of M. vulgare aqueous extract to further support their traditional use. Qualitative phytochemical tests of M. vulgare extracts showed the presence of primary and secondary metabolites, while quantitative analyses recorded revealed the contents of total phenols, flavonoids, and tannins, with values of 488.432 ± 7.825 mg/EAG gallic acid extract/g, 25.5326 ± 1.317 mg/EQ Quercetin extract/g and 23.966 ± 0.187 mg/EC catechin extract/g, respectively. Characterization of the phytochemical constituents of the extract revealed the presence of catechin and maleic acid as the most abundant while the evaluation of the antioxidant power revealed that the extract possesses significant antioxidant capacity, antimitotic potential, and antimicrobial properties against Streptococcus agalactiae and Staphylococcus epidermidis among many others. The antidiabetic activity of the extract showed a potent antihyperglycemic effect and a significant modulation of the pancreatic α-amylase activity as revealed by both in vitro and in vivo analysis, while an in silico evaluation showed that chemicals in the studied extract exhibited the aforementioned activities by targeting 1XO2 antimitotic protein, W93 antidiabetic protein and 1AJ6 antimicrobial protein, which revealed them as worthy of exploration in drug discovery odyssey. Conclusively, the result of this study demonstrates the numerous biological activities of M. vulgare and gives credence to their folkloric and traditional usage.
Antibacterial activity of the novel compound Sudapyridine (WX-081) against Mycobacterium abscessus
Authors: Nie Wenjuan , Gao Shan , Su Lei , Liu Lina , Geng Ruixue , You Yingxia , Chu Naihui
Published: August 2023

Objective

This study aimed to investigate sudapyridine (WX-081) antibacterial activity against Mycobacterium abscessus in vitro and its effect on in vivo bacterial growth and host survival using a zebrafish model of M. abscessus infection.

Methods

WX-081 in vitro antibacterial activity was assessed based on growth inhibition of M. abscessus standard strain ATCC19977 and 36 clinical isolates. Maximum tolerated concentrations (MTCs) of WX-081, bedaquiline, and azithromycin and inhibition of M. abscessus growth were assessed in vivo after fluorescently labelled bacilli and drugs were injected into zebrafish. Bacterial counts were analysed using one-way ANOVA and fluorescence intensities of zebrafish tissues were analysed and expressed as the mean ± SE. Moreover, Kaplan-Meier survival analysis was conducted to assess intergroup differences in survival of M. abscessus-infected zebrafish treated with different drug concentrations using a log-rank test, with a p value <0.05 indicating a difference was statistically significant.

Results

Drug sensitivity testing of M. abscessus standard strain ATCC19977 and 36 clinical isolates revealed MICs ranging from 0.12-0.96 µg/mL and MIC50 and MIC90 values of 0.48 µg/mL and 0.96 µg/mL, respectively. Fluorescence intensities of M. abscessus-infected zebrafish tissues was lower after treatment with the WX-081 MTC (62.5 µg/mL) than after treatment with the azithromycin MTC (62.5 µg/mL) and the bedaquiline MTC (15.6 µg/mL). When the concentration of WX-081 increased from 1.95µg/mL to 1/8 MTC(7.81µg/mL), the survival rate of zebrafish at 4-9 dpf decreased from 90.00% to 81.67%.

Conclusion

WX-081 effectively inhibited M. abscessus growth in vitro and in vivo and prolonged survival of M. abscessus-infected zebrafish, thus indicating that WX-081 holds promise as a clinical treatment for M. abscessus infection.
Application of CRISPR-Cas system in the diagnosis and therapy of ESKAPE infections
Authors: Qian Yizheng , Zhou Dapeng , Li Min , Zhao Yongxiang , Liu Huanhuan , Yang Li , Ying Zhiqin , Huang Guangtao
Published: August 2023

Antimicrobial-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. ESKAPE pathogens are the most common opportunistic pathogens in nosocomial infections, and a considerable number of their clinical isolates are not susceptible to conventional antimicrobial therapy. Therefore, innovative therapeutic strategies that can effectively deal with ESKAPE pathogens will bring huge social and economic benefits and ease the suffering of tens of thousands of patients. Among these strategies, CRISPR (clustered regularly interspaced short palindromic repeats) system has received extra attention due to its high specificity. Regrettably, there is currently no direct CRISPR-system-based anti-infective treatment. This paper reviews the applications of CRISPR-Cas system in the study of ESKAPE pathogens, aiming to provide directions for the research of ideal new drugs and provide a reference for solving a series of problems caused by multidrug-resistant bacteria (MDR) in the post-antibiotic era. However, most research is still far from clinical application.
Antiviral effects of interferon-stimulated genes in bats
Authors: Zhang Dan , Irving Aaron T.
Published: August 2023

The interferon pathway is the first line of defense in viral infection in all mammals, and its induction stimulates broad expression of interferon-stimulated genes (ISGs). In mice and also humans, the antiviral function of ISGs has been extensively studied. As an important viral reservoir in nature, bats can coexist with a variety of pathogenic viruses without overt signs of disease, yet only limited data are available for the role of ISGs in bats. There are multiple species of bats and work has begun deciphering the differences and similarities between ISG function of human/mouse and different bat species. This review summarizes the current knowledge of conserved and bat-specific-ISGs and their known antiviral effector functions.
Genetic diversity of Leptospira strains circulating in humans and dogs in France in 2019-2021
Authors: Garcia-Lopez Marta , Lorioux Celine , Soares Anais , Trombert-Paolantoni Sabine , Harran Elena , Ayral Florence , Picardeau Mathieu , Djelouadji Zouheira , Bourhy Pascale
Published: August 2023

Leptospirosis is a bacterial zoonotic disease. Humans and dogs are susceptible hosts, with similar clinical manifestations ranging from a febrile phase to multiple organ dysfunction. The incidence of leptospirosis in mainland France is relatively high, at about 1 case per 100,000 inhabitants, but our knowledge of the strains circulating in humans and dogs remains limited. We studied the polymorphism of the lfb1 gene sequences in an exhaustive database, to facilitate the identification of Leptospira strains. We identified 46 species-groups (SG) encompassing the eight pathogenic species of Leptospira. We sequenced the lfb1 gene amplification products from 170 biological samples collected from 2019 to 2021: 110 from humans and 60 from dogs. Epidemiological data, including vaccination status in dogs, were also collected. Three Leptospira species displaying considerable diversity were identified: L. interrogans, with eight lfb1 species-groups (including five new lfb1 species-groups) in humans and dogs; L. kirschneri, with two lfb1 species-groups in humans and dogs; and L. borgpetersenii, with one lfb1 species-group in humans only. The lfb1 species-group L. interrogans SG1, corresponding to serovar Icterohaemorrhagiae or Copenhageni, was frequently retrieved from both humans and dogs (n=67/110; 60.9% and n=59/60; 98.3% respectively). A high proportion of the affected dogs developed the disease despite vaccination (n=30/60; 50%). Genotyping with the polymorphic lfb1 gene is both robust and simple. This approach provided the first global picture of the Leptospira strains responsible for acute infections in mainland France, based on biological samples but without the need for culture. Identification of the Leptospira strains circulating and their changes over time will facilitate more precise epidemiological monitoring of susceptible and reservoir species. It should also facilitate the monitoring of environmental contamination, making it possible to implement preventive measures and to reduce the burden of this disease.
Lactobacillus reuteri in digestive system diseases: focus on clinical trials and mechanisms
Authors: Peng Yijing , Ma Yizhe , Luo Zichen , Jiang Yifan , Xu Zhimin , Yu Renqiang
Published: August 2023

Objectives

Digestive system diseases have evolved into a growing global burden without sufficient therapeutic measures. Lactobacillus reuteri (L. reuteri) is considered as a new potential economical therapy for its probiotic effects in the gastrointestinal system. We have provided an overview of the researches supporting various L. reuteri strains’ application in treating common digestive system diseases, including infantile colic, diarrhea, constipation, functional abdominal pain, Helicobacter pylori infection, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases.

Methods

The summarized literature in this review was derived from databases including PubMed, Web of Science, and Google Scholar.

Results

The therapeutic effects of L. reuteri in digestive system diseases may depend on various direct and indirect mechanisms, including metabolite production as well as modulation of the intestinal microbiome, preservation of the gut barrier function, and regulation of the host immune system. These actions are largely strain-specific and depend on the activation or inhibition of various certain signal pathways. It is well evidenced that L. reuteri can be effective both as a prophylactic measure and as a preferred therapy for infantile colic, and it can also be recommended as an adjuvant strategy to diarrhea, constipation, Helicobacter pylori infection in therapeutic settings. While preclinical studies have shown the probiotic potential of L. reuteri in the management of functional abdominal pain, inflammatory bowel disease, diverticulitis, colorectal cancer and liver diseases, its application in these disease settings still needs further study.

Conclusion

This review focuses on the probiotic effects of L. reuteri on gut homeostasis via certain signaling pathways, and emphasizes the importance of these probiotics as a prospective treatment against several digestive system diseases.
Depressive and anxiety disorders and antidepressant prescriptions among insured children and young adults with congenital adrenal hyperplasia in the United States
Authors: Harasymiw Lauren A. , Grosse Scott D. , Cullen Kathryn R. , Bitsko Rebecca H. , Perou Ruth , Sarafoglou Kyriakie
Published: August 2023

Background

Dysfunction in the hypothalamic-pituitary-adrenal axis has been associated with depressive and anxiety disorders. Little is known about the risk for these disorders among individuals with congenital adrenal hyperplasia (CAH), a form of primary adrenal insufficiency.

Objective

We investigated the prevalence of depressive and anxiety disorders and antidepressant prescriptions in two large healthcare databases of insured children, adolescents, and young adults with CAH in the United States.

Methods

We conducted a retrospective cohort study using administrative data from October 2015 through December 2019 for individuals aged 4–25 years enrolled in employer-sponsored or Medicaid health plans.

Results

Adjusting for age, the prevalence of depressive disorders [adjusted prevalence ratio (aPR) = 1.7, 95% confidence interval (CI): 1.4-2.0, p<0.001], anxiety disorders [aPR = 1.7, 95% CI: 1.4-1.9, p<0.001], and filled antidepressant prescriptions [aPR = 1.7, 95% CI: 1.4-2.0, p<0.001] was higher among privately insured youth with CAH as compared to their non-CAH peers. Prevalence estimates were also higher among publicly insured youth with CAH for depressive disorders [aPR = 2.3, 95% CI: 1.9-2.9, p<0.001], anxiety disorders [aPR = 2.0, 95% CI: 1.6-2.5, p<0.001], and filled antidepressant prescriptions [aPR = 2.5, 95% CI: 1.9-3.1, p<0.001] as compared to their non-CAH peers.

Conclusions

The elevated prevalence of depressive and anxiety disorders and antidepressant prescriptions among youth with CAH suggests that screening for symptoms of depression and anxiety among this population might be warranted.
Obtaining SF-6D utilities from FACT-H&N in thyroid carcinoma patients: development and results from a mapping study
Authors: Yang Qing , Huang Deyu , Jiang Longlin , Tang Yuan , Zeng Dingfen
Published: August 2023

Objective

There is limited evidence for mapping clinical tools to preference-based generic tools in the Chinese thyroid cancer patient population. The current study aims to map the FACT-H&N (Functional Assessment of Cancer Therapy-Head and Neck Cancer) to the SF-6D (Short Form Six-Dimension), which will inform future cost-utility analyses related to thyroid cancer treatment.

Methods

A total of 1050 participants who completed the FACT-H&N and SF-6D questionnaires were included in the analysis. Four methods of direct and indirect mapping were estimated: OLS regression, Tobit regression, ordered probit regression, and beta mixture regression. We evaluated the predictive performance in terms of root mean square error (RMSE), mean absolute error (MAE), concordance correlation coefficient (CCC), Akaike information criterion (AIC) and Bayesian information criterion (BIC) and the correlation between the observed and predicted SF-6D scores.

Results

The mean value of SF-6D was 0.690 (SD = 0.128). The RMSE values for the fivefold cross-validation as well as the 30% random sample validation for multiple models in this study were 0.0833-0.0909, MAE values were 0.0676-0.0782, and CCC values were 0.6940-0.7161. SF-6D utility scores were best predicted by a regression model consisting of the total score of each dimension of the FACT-H&N, the square of the total score of each dimension, and covariates including age and gender. We proposed to use direct mapping (OLS regression) and indirect mapping (ordered probit regression) to establish a mapping model of FACT-H&N to SF-6D. The mean SF-6D and cumulative distribution functions simulated from the recommended mapping algorithm generally matched the observed ones.

Conclusions

In the absence of preference-based quality of life tools, obtaining the health status utility of thyroid cancer patients from directly mapped OLS regression and indirectly mapped ordered probit regression is an effective alternative.
Ferroptosis and its potential role in gestational diabetes mellitus: updated evidence from pathogenesis to therapy
Authors: Zhao Yan , Gao Qianqian , Li Baoxuan , Wang Yang , Wang Yue
Published: August 2023

Background

Studies have demonstrated that high iron status is positively associated with gestational diabetes mellitus (GDM), implying that iron overload and ferroptosis play important roles in the development of GDM. The aim of this study was to explore effective therapeutic drugs from traditional Chinese medicine (TCM)formulas for the treatment of GDM based on ferroptosis.

Methods

In this study, the presence of ferroptosis in the placenta was verified through clinical and experimental data, and key genes were subsequently screened for association with ferroptosis in the development of GDM. The analysis was based on transcriptome sequencing of datasets combined with differentially expressed genes (DEGs) analysis and weighted gene correlation network analysis (WGCNA); functional enrichment analysis was also performed. A protein−protein interaction (PPI) network was constructed and pivotal genes were identified using Cytoscape. Finally, traditional Chinese medicine (TCM)formulas related to treating GDM were collected, then the proteins corresponding to the key genes were molecularly docked with the small molecular structures of clinically proven effective herbal tonics, and molecular dynamic simulations were performed to select the best candidates for pharmacological compounds.

Results

Elevated ferritin levels in patients with GDM were verified using clinical data. The presence of ferroptosis in placental tissues of patients with GDM was confirmed using electron microscopy and western blotting. Ninety-nine key genes with the highest correlation with ferroptosis were identified from DEGs and weighted gene co-expression network analysis (WGCNA). Analysis using the Kyoto Encyclopedia of Genes and Genomes demonstrated that the DEGs were primarily involved in the oxidative phosphorylation pathway. The key genes were further screened by PPI; two key genes, SF3B14 and BABAM1, were identified by combining the gene corresponding to protein structure and function, followed by molecular docking and molecular dynamic simulation. Coptis chinensis was proposed as the best candidate for herbal treatment at the molecular level.

Conclusion

This data revealed the presence of ferroptosis in patients with GDM and identified possible modulatory roles of ferroptosis-related genes involved in the molecular mechanisms of GDM, providing new insights into the pathogenesis of GDM, which also provided new directions for the systematic optimization of TCM formulas for the management and targeted treatment of GDM.
Abnormal glucose homeostasis and fasting intolerance in patients with congenital porto-systemic shunts
Authors: van Albada Mirjam E. , Shah Pratik , Derks Terry G. J. , Fuchs Sabine , Jans Judith J. M. , McLin Valérie , van der Doef Hubert P. J.
Published: August 2023

In physiological glucose homeostasis, the liver plays a crucial role in the extraction of glucose from the portal circulation and storage as glycogen to enable release through glycogenolysis upon fasting. In addition, insulin secreted by the pancreas is partly eliminated from the systemic circulation by hepatic first-pass. Therefore, patients with a congenital porto-systemic shunt present a unique combination of (a) postabsorptive hyperinsulinemic hypoglycaemia (HH) because of decreased insulin elimination and (b) fasting (ketotic) hypoglycaemia because of decreased glycogenolysis. Patients with porto-systemic shunts therefore provide important insight into the role of the portal circulation and hepatic function in different phases of glucose homeostasis.
Current status and progress in research on dressing management for diabetic foot ulcer
Authors: Jiang Pingnan , Li Qianhang , Luo Yanhong , Luo Feng , Che Qingya , Lu Zhaoyu , Yang Shuxiang , Yang Yan , Chen Xia , Cai Yulan
Published: August 2023

Diabetic foot ulcer (DFU) is a major complication of diabetes and is associated with a high risk of lower limb amputation and mortality. During their lifetime, 19%–34% of patients with diabetes can develop DFU. It is estimated that 61% of DFU become infected and 15% of those with DFU require amputation. Furthermore, developing a DFU increases the risk of mortality by 50%–68% at 5 years, higher than some cancers. Current standard management of DFU includes surgical debridement, the use of topical dressings and wound decompression, vascular assessment, and glycemic control. Among these methods, local treatment with dressings builds a protective physical barrier, maintains a moist environment, and drains the exudate from DFU wounds. This review summarizes the development, pathophysiology, and healing mechanisms of DFU. The latest research progress and the main application of dressings in laboratory and clinical stage are also summarized. The dressings discussed in this review include traditional dressings (gauze, oil yarn, traditional Chinese medicine, and others), basic dressings (hydrogel, hydrocolloid, sponge, foam, film agents, and others), bacteriostatic dressings, composite dressings (collagen, nanomaterials, chitosan dressings, and others), bioactive dressings (scaffold dressings with stem cells, decellularized wound matrix, autologous platelet enrichment plasma, and others), and dressings that use modern technology (3D bioprinting, photothermal effects, bioelectric dressings, microneedle dressings, smart bandages, orthopedic prosthetics and regenerative medicine). The dressing management challenges and limitations are also summarized. The purpose of this review is to help readers understand the pathogenesis and healing mechanism of DFU, help physicians select dressings correctly, provide an updated overview of the potential of biomaterials and devices and their application in DFU management, and provide ideas for further exploration and development of dressings. Proper use of dressings can promote DFU healing, reduce the cost of treating DFU, and reduce patient pain.
Zebrafish as an emerging model to study estrogen receptors in neural development
Authors: Boueid Marie-José , El-Hage Océane , Schumacher Michael , Degerny Cindy , Tawk Marcel
Published: August 2023

Estrogens induce several regulatory signals in the nervous system that are mainly mediated through estrogen receptors (ERs). ERs are largely expressed in the nervous system, yet the importance of ERs to neural development has only been elucidated over the last decades. Accumulating evidence shows a fundamental role for estrogens in the development of the central and peripheral nervous systems, hence, the contribution of ERs to neural function is now a growing area of research. The conservation of the structure of the ERs and their response to estrogens make the zebrafish an interesting model to dissect the role of estrogens in the nervous system. In this review, we highlight major findings of ER signaling in embryonic zebrafish neural development and compare the similarities and differences to research in rodents. We also discuss how the recent generation of zebrafish ER mutants, coupled with the availability of several transgenic reporter lines, its amenability to pharmacological studies and in vivo live imaging, could help us explore ER function in embryonic neural development.
Physiopathological role of extracellular vesicles in alloimmunity and kidney transplantation and their use as biomarkers
Authors: Cuadrado-Payán Elena , Ramírez-Bajo María José , Bañón-Maneus Elisenda , Rovira Jordi , Diekmann Fritz , Revuelta Ignacio , Cucchiari David
Published: August 2023

Antibody-mediated rejection is the leading cause of kidney graft dysfunction. The process of diagnosing it requires the performance of an invasive biopsy and subsequent histological examination. Early and sensitive biomarkers of graft damage and alloimmunity are needed to identify graft injury and eventually limit the need for a kidney biopsy. Moreover, other scenarios such as delayed graft function or interstitial fibrosis and tubular atrophy face the same problem. In recent years, interest has grown around extracellular vesicles, specifically exosomes actively secreted by immune cells, which are intercellular communicators and have shown biological significance. This review presents their potential as biomarkers in kidney transplantation and alloimmunity.
The association between non-alcoholic fatty liver disease and atopic dermatitis: a population-based cohort study
Authors: Gau Shuo-Yan , Huang Ching-Hua , Yang Yih , Tsai Tung-Han , Huang Kuang-Hua , Lee Chien-Ying
Published: August 2023

Background

In previous studies, it was reported that non-alcoholic fatty liver disease (NAFLD) incidence and prevalence increased in children with atopic dermatitis. Nevertheless, the actual association between the two diseases has not been fully proven in large-scale studies, and real-world evidence is missing. The objective of this nationwide, longitudinal cohort study was to evaluate the association between NAFLD and atopic dermatitis.

Methods

The National Health Insurance Research Database in Taiwan was utilized in this study. Patients with records of NAFLD diagnosis were recruited as the experimental group, and patients having less than three outpatient visits or one inpatient visiting record due to NAFLD were excluded from the study design. Non-NAFLD controls were matched based on a 1:4 propensity score matching. Potential confounders including age, gender, comorbidity, and medical utilization status were considered as covariates. The risk of future atopic dermatitis would be evaluated based on multivariate Cox proportional hazard regression.

Results

Compared with people without NAFLD, a decreased risk of atopic dermatitis in NALFD patients had been observed (aHR = 0.93, 95% CI 0.87–0.98). The trend was especially presented in young NAFLD patients. In patients younger than 40 years old, a 20% decreased risk of atopic dermatitis was reported (aHR = 0.80, 95% CI 0.70–0.92).

Conclusion

People with NAFLD were not associated with an increased risk of atopic dermatitis. Conversely, a 0.93-fold risk was noted in NAFLD patients, compared with NAFLD-free controls. Future studies are warranted to evaluate further the mechanism regarding the interplay between the inflammatory mechanisms of NAFLD and atopic dermatitis.
Allele-specific quantification of human leukocyte antigen transcript isoforms by nanopore sequencing
Authors: Hughes Andrew E. O. , Montgomery Maureen C. , Liu Chang , Weimer Eric T.
Published: August 2023

Introduction

While tens of thousands of HLA alleles have been identified by DNA sequencing, the contribution of alternative splicing to HLA diversity is not well characterized. In this study, we sought to determine if long-read sequencing could be used to accurately quantify allele-specific HLA transcripts in primary human lymphocytes.

Methods

cDNA libraries were prepared from peripheral blood lymphocytes from 12 donors and sequenced by nanopore long-read sequencing. HLA reads were aligned to donor-specific reference sequences based on the known type of each donor. Allele-specific exon utilization was calculated as the proportion of reads aligning to each allele containing known exons, and transcript isoforms were quantified based on patterns of exon utilization within individual reads.

Results

Splice variants were rare among class I HLA genes (median exon retention rate 99%–100%), except for several HLA-C alleles with exon 5 spliced out of up to 15% of reads. Splice variants were also rare among class II HLA genes (median exon retention rate 98%–100%), except for HLA-DQB1. Consistent with previous work, exon 5 of HLA-DQB1 was spliced out in alleles with a mutated splice acceptor site at rs28688207. Surprisingly, a 28% loss of exon 5 was also observed in HLA-DQB1 alleles with an intact splice acceptor site at rs28688207.

Discussion

We describe a simple bioinformatic workflow to quantify allele-specific expression of HLA transcript isoforms. Further studies are warranted to characterize the repertoire of HLA transcripts expressed in different cell types and tissues across diverse populations.
Serum CHI3L1 as a biomarker of interstitial lung disease in rheumatoid arthritis
Authors: Yu Rui , Liu Xiaomin , Deng Xiaoyue , Li Siting , Wang Yifei , Zhang Yan , Ke Dan , Yan Rui , Wang Qian , Tian Xinping , Li Mengtao , Zeng Xiaofeng , Hu Chaojun
Published: August 2023

Background

Interstitial lung disease (ILD) is a relatively prevalent extra-articular manifestation of rheumatoid arthritis (RA) and contributes to significant morbidity and mortality. This study aimed to analyze the association between chitinase-3 like-protein-1(CHI3L1) and the presence of RA-ILD.

Methods

A total of 239 RA patients fulfilling the American Rheumatism Association (ACR) 1987 revised criteria were enrolled and subclassified as RA-ILD and RA-nILD based on the results of high-resolution computed tomography scans (HRCT) of the chest. The disease activity of RA was assessed by Disease Activity Score for 28 joints (DAS28) and categorized as high, moderate, low, and remission. Chemiluminescence immunoassays were applied to determine the serum levels of CHI3L1. Univariate analysis was performed and the receiver operating characteristics (ROC) curves were plotted to evaluate the correlation between RA-ILD and CHI3L1.

Results

Among the eligible RA patients studied, 60 (25.1%) patients were diagnosed with RA-ILD. Compared with RA-nILD, RA patients with ILD had significantly higher median age (median [IQR], 68.00 [62.00-71.75] vs 53.00 [40.00-63.00], p<0.001) and a higher proportion of males (21 (35.0%) vs 30 (16.8%), p=0.003). Notably, differences in DAS28 scores between the two groups were not observed. The serum level of CHI3L1 was significantly higher in RA-ILD patients (median [IQR], 69.69 [44.51-128.66] ng/ml vs 32.19 [21.63-56.99] ng/ml, p<0.001). Furthermore, the areas under the curve (AUC) of CHI3L1 attained 0.74 (95% confidence interval [CI], 0.68-0.81, p<0.001) in terms of identifying patients with RA-ILD from those without ILD. Similar trends were seen across the spectrum of disease activity based on DAS28-ESR.

Conclusion

Our findings of elevated serum CHI3L1 levels in RA-ILD patients suggest its possible role as a biomarker to detect RA-ILD noninvasively.
The impact of immunoglobulin G N-glycosylation level on COVID-19 outcome: evidence from a Mendelian randomization study
Authors: Long Feiwu , Xiao Chenghan , Cui Huijie , Wang Wei , Jiang Zongze , Tang Mingshuang , Zhang Wenqiang , Liu Yunjie , Xiang Rong , Zhang Li , Zhao Xunying , Yang Chao , Yan Peijing , Wu Xueyao , Wang Yutong , Zhou Yanqiu , Lu Ran , Chen Yulin , Li Jiayuan , Jiang Xia , Fan Chuanwen , Zhang Ben
Published: August 2023

Background

The coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID‐19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial.

Methods

We conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran’s Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results.

Results

We found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92–0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy.

Conclusions

Our study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels.