bluuebunny/crossref_metadata_2025 huggingface dataset:
Thiourea Supplementation Improves Drought Stress Response of Ridge‐Sown and Mulch‐Applied Rainfed Maize (Zea mays L.) via Improved Leaf Source to Grain Sink Dynamics
Authors: Singh Talveer , Sandhu Parminder Singh , Darrouzet‐Nardi Anthony
Published: September 2024

In regions of South Asia where rainfed maize is grown, effective crop management during drought is essential for maximising yield. A variety of water‐conserving planting practices are used, and more recently, techniques such as foliar supplementation to maintain nutrients during drought have also shown promise. However, specific combinations of these approaches are often untested for optimality. Here, we explore the effects of two maize planting practices (ridge sowing and mulching) to conserve water, in combination with foliar thiourea. Drought stress response of crop was assessed at two experimental sites (L‐I and L‐II), through split‐plot design (main plots: flat sowing + mulch, flat sowing, ridge sowing + mulch [RS + M] and ridge sowing; sub‐plots: unsprayed, water spray, 500 ppm thiourea and 1000 ppm thiourea). Plant performance was assessed via dry matter accumulation, grain growth rate, stomatal parameters, grain yield, stover yield and nitrogen uptake. Rainfall breaks induced three dry spells during the pre‐anthesis and grain‐filling period. RS + M showed maximum drought tolerance by enhancing rainwater and nutrient use (N uptake [88.1 and 115.1 kg ha−1]) and recorded significantly higher periodic dry matter accumulation (149.2 and 156.8 g) along with higher 1000‐grain weight (181.0 and 196.6 g), grain‐filling duration (36.3 and 34.9 days) and leaf health parameters over the flat‐sown treatments. Furthermore, foliar supplementation of thiourea at 1000 ppm caused improved leaf health, likely through activation of a source to sink response (transfer of energy and materials from leaves to other plant organs) that alleviated moisture stress. Ultimately, the combination of RS + M and 1000 ppm thiourea led to the highest grain yields (32.1 and 39.5 qha−1).
Integrative taxonomy reveals a new species of Characidium (Characiformes: Crenuchidae) shared by tributaries of upper Tapajós and Xingu river basins, Brazil
Authors: Zanata Angela Maria , Oliveira Claudio , Oliveira‐Silva Leonardo
Published: September 2024

A new species of Characidium shared by adjacent tributaries of the upper portions of the Tapajós and Xingu river basins is described. Characidium varii, new species, can be distinguished from the congeners by having distinctly speckled pattern of colouration, including dark blotches on cheek and ventral surface of head, by having conspicuous dark marks on fins, along with a single row of dentary teeth, isthmus completely covered by scales, 14 circumpeduncular scales, and swimbladder reduced. Molecular data reinforce the validation of the new species. The distribution of C. varii supports the hypothesis of the existence of a faunistic mixing between Tapajós and Xingu river basins, corresponding to the region of the Serra do Cachimbo and surrounding areas, previously proposed in the literature.
Identifying marginal adaptation discrepancies of lithium disilicate crowns using seven different vertical X‐ray angulations
Authors: Carvalho Luiz , Becker Ryan , Oyoyo Udochukwu , Rice Dwight D. , Kattadiyil Mathew T.
Published: September 2024

Purpose

To study the effect of different vertical angulations on the ability to radiographically assess vertical marginal discrepancies of lithium disilicate crowns.

Materials and Methods

Twenty‐one lithium disilicate crowns were fabricated for three different prepared natural teeth: incisor, canine, and premolar. Vertical marginal discrepancies ranging from 0 to 300 µm were intentionally created. The seated crowns were radiographed using seven different vertical angulations, totaling 147 images. Thirty experienced evaluators scored each image for marginal discrepancy, and values were statistically analyzed.

Results

Significant differences in the ability to accurately assess marginal discrepancies from radiographs were observed for the study factors of angulation, tooth type, and degree of marginal discrepancy (p < 0.001).

Conclusions

The radiographic interpretation of the marginal discrepancies of lithium disilicate crowns is significantly affected by the dimension of the marginal discrepancy. Specifically on premolar crowns, it is significantly affected by different vertical angulations of the X‐ray beam. When evaluating marginal discrepancy on lithium disilicate crowns radiographically, vertical beam angulation within ±10° to the cemento‐enamel junctionCEJ plane is recommended.
A single center experience on PI3K/AKT/MTOR signaling defects: Towards pathogenicity assessment for four novel defects
Authors: Bildik Hacer Neslihan , Esenboga Saliha , Halaclı Sevil Oskay , Karaatmaca Betül , Aytekin Elif Soyak , Nabiyeva Nadira , Akarsu Ayşegul , Ocak Melike , Erman Baran , Tan Cagman , Arikoglu Tugba , Yaz Ismail , Cicek Begum , Tezcan Ilhan , Cagdas Deniz
Published: September 2024

Background

Phosphoinositide 3 kinases (PI3K) are lipid kinases expressed in lymphocytes/myeloid cells. PI3K/AKT/mTOR signaling defects present with recurrent infections, autoimmunity, lymphoproliferation, and agammaglobulinemia.

Objective

To characterize the PI3K/AKT/mTOR pathway defects and perform pathway analyses to assess novel variant pathogenicity.

Methods

We included 12 patients (heterozygous PIK3CD (n = 9) and PIK3R1 (n = 1) (activated PI3K delta syndrome (APDS) with gain‐of‐function mutations) and homozygous PIK3R1 variant (n = 2)), performed clinical/laboratory/genetic evaluation, and flow cytometric PI3K/AKT/mTOR pathway analyses.

Results

Median age at onset of complaints was 17.5 months (3 months to 12 years) and at diagnosis was 15.7 years (2.5–37) in APDS. Median diagnostic delay was 12.9 years (1.6–27). Recurrent respiratory tract infections (90%), lymphoproliferation (70%), autoimmune/inflammatory findings (60%), and allergy (40%) were common in APDS. Recurrent viral infections were present in 4/10 and malignancy (non‐Hodgkin lymphoma and testicular yolk sac tumor) was present in 2/10 in APDS. Low CD4+ T cells(5/8) with increased CD4+ effector memory (8/8) and CD4+ TEMRA cells (6/8) were present in the given number of APDS patients. We diagnosed tubulointerstitial nephritis, Langerhans cell histiocytosis, and late‐onset congenital adrenal hyperplasia in APDS. Allergic findings, lymphoproliferation/malignancy, and high IgM were present in the APDS but not in PIK3R1 deficiency. Low IgM/IgG/CD19+ B cell counts were characteristic in patients with PIK3R1 homozygous loss‐of function mutations.

Conclusion

Differential diagnosis with combined immunodeficiency and diseases of immune dysregulation make molecular genetic analysis crucial for diagnosing mTOR pathway defects. It is easy to differentiate APDS and homozygous PIK3R1 defects with specific laboratory features. Additionally, mTOR pathway functional analysis is a definitive diagnostic and pathogenicity assessment tool for novel APDS mutations.

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The Effects of the StartReact on Reaction Time, Rate of Force Development, and Muscle Activity in Biceps Brachii
Authors: Walker Simon , Tanel Meghan , Vekki Sakari , Kidgell Dawson J. , Baker Stuart N.
Published: September 2024

The StartReact test, increasingly popular for assessing cortico‐reticular functioning, is a valid method to influence the firing of reticulospinal tract neurons noninvasively. However, there remains limited evidence on how different stimuli employed in the StartReact test impact motor output in humans. The present study tested elbow flexor responses of 33 adults (aged 26–48 years) to visual stimuli only (LED light), audio‐visual (80 dB) stimuli, and startle‐inducing audio‐visual (120 dB) stimuli sitting with the arm supinated in an electromechanical dynamometer. Surface electromyogram (EMG) recorded muscle activity from the right biceps brachii muscle. Participants were presented with 20 stimuli for each of the three conditions in pseudorandom order with interstimulus intervals of ~8 s. Reaction times were calculated from the stimulus trigger to the initial rise in the EMG signal above 7 × SD from baseline. Rate of torque development (RTD) and EMG signals were recorded throughout and analyzed over their initial 50 ms and 100 ms time‐windows. Reaction times were reduced from visual (169 ± 23) to audio‐visual (140 ± 23) and further reduced to startle‐inducing audio‐visual stimuli (108 ± 19, p < 0.001). While RTD and EMG were consistently greatest following startle‐inducing stimuli (p < 0.001), they were also enhanced following all audio‐visual stimuli over 100 ms (p < 0.05). It appears that startle‐inducing audio‐visual stimuli result in shorter reaction times, increased RTD, and enhanced muscle activity within the initial 50 ms, likely from subcortical upregulation. However, the 100 ms time‐window suggests cortical upregulation following all audio‐visual stimuli considering the longer transmission times.
Detection of the HLA‐B*51:01:44 allele in a Taiwanese individual
Authors: Yang Kuo‐Liang , Lin Py‐Yu
Published: September 2024

Nucleotide substitution in codon 221 of HLA‐B*51:01:01:01 results in a novel allele, HLA‐B*51:01:44.
Assessment of Urban Environmental Quality by Socioeconomic and Environmental Variables Using Open‐Source Datasets
Authors: Lingye Tan , Saleem Nayyer , Aslam Rana Waqar , Sajjad Asif , Naz Iram , Tariq Aqil , Alzahrani Hassan
Published: September 2024

In this era of rapid development, environmental quality is an essential aspect of sustainable development. A healthy urban environment supports, regulates, and provides livable conditions. In urban areas, environmental quality is considerably affected by socioeconomic factors such as population expansion and economic development. For decision‐making, it is also significant for stakeholders and policymakers to understand the impact of urban expansion on environmental quality. While previous studies have examined urban environmental quality, they often focused on single cities or limited environmental parameters. This research addresses these limitations by conducting a comparative analysis of two major Asian cities with similar demographic features, utilizing a comprehensive set of socioeconomic and environmental variables. Our innovative approach combines open‐source datasets with advanced remote sensing techniques to provide a more holistic assessment of urban environmental quality over two decades. We analyzed urban environmental quality for last two decades with the selected urban environmental quality parameters: surface greenness, surface moisture, and land surface temperature. Lahore (Pakistan) and Wuhan (China) cities were selected for having approximately same demographic features. Correlation matrix has been used to assess the relationship between these environmental variables and social‐economic variables: urban expansion and carbon emission. Correlation coefficient indicated that urban expansion correlates negatively with surface greenness and surface moisture for both Lahore (−0.67 and −0.71) and Wuhan District (−0.5 and −0.75), respectively, while it had a positive relation with land surface temperature: 0.65 and 0.57 for Lahore and Wuhan District, respectively. These effects are more prominent within 10 km distance from the city center, where a substantial urban expansion is observed during the time window.
ВЗАИМОСВЯЗЬ МЕЖДУ ТУБЕРКУЛЕЗОМ С МНОЖЕСТВЕННОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ И СЕМЕЙСТВОМ BEIJING M.TUBERCULOSIS ЦИРКУЛИРУЮЩИХ НА ТЕРРИТОРИИ КАЗАХСТАНА
Authors: Абилова Ж. , Ахметова A. , Сатвалдина Н. , Данияров А. , Каиров У. , Акильжанова А. , Алмазан Дж. , Кожамкулов У.
Published: September 2024

ТБ по данным ВОЗ на 2021–2025 годы. Цель исследования – определение связи МЛУ с семейством Beijing M.tuberculosis, а также дальнейший геномный анализ данных полногеномного секвенирования клинических изолятов МЛУ M.tuberculosis, распространенных в Казахстане.
В разных регионах Казахстана собрано 271 лекарственно-устойчивый M.tuberculosis от больных туберкулезом, в том числе 143 (52,77%) - МЛУ, 79 (29,15%) - пре-ШЛУ, 21 (7,75%) - монорезистентные, 19 (7,01%). ) – полирезистентными, а 9 (3,32) – ШЛУ к противотуберкулезным препаратам. Семьдесят шесть хорошо охарактеризованных штаммов MDR были отобраны для дальнейшего геномного анализа. Сполиготипирование проводили с использованием коммерчески доступного набора MeltPro® McSpoligotyping Test Kit, Zeesan. Устойчивость к противотуберкулезным препаратам первого ряда определяли с помощью системы BACTEC MGIT-960. Секвенирование проводили на NovoSeq 6000 (Illumina, США).
Результаты генотипирования 76 изолятов МЛУ показали преобладание семейства Beijing M.tuberculosis, которое выявлено в 85,5% случаев (65 клинических изолятов). Остальные изоляты принадлежали к следующим семействам: LAM9 – 3 (3,9%), LAM-RUS – 3 (3,9%), T1 – 2 (2,6%), H3 – 1 (1,3%), MANU2 – 1 (1,3%), С – 1 (1,3%). Сочетание лекарственной устойчивости к трем основным противотуберкулезным препаратам - изониазиду, рифампицину и этамбутолу было наиболее частым и выявлено в 23 случаях (30,2%). Устойчивость к изониазиду, рифампицину, пиразинамиду и этамбутолу выявлена ​​у 21 изолята (27,6%). Устойчивость к изониазиду, рифампицину и пиразинамиду выявлена ​​в 17 случаях (22.4%), а устойчивость к изониазиду и рифампицину выявлена ​​в 15 случаях (19,7%).
Генотип Beijing M.tuberculosis оказался наиболее распространенным среди изолятов МЛУ, циркулирующих в Казахстане. Дальнейший геномный анализ с использованием TB-Profiler, MTBseq, mykrobe, PATRIC и других баз данных позволит проанализировать данные секвенирования генома клинических изолятов M.tuberculosis и определить генетический профиль общей лекарственной устойчивости.
Ссылки на гранты: данное исследование было профинансировано за счет гранта Назарбаев Университета в рамках Программы совместных исследований №11022021CRP1511.
El lado agridulce de la panela: comprensiones del cambio tecnológico en una controversia mediática por una patente
Authors: Montes Cruz José Joaquín , Franco Forero Carlos David
Published: September 2024

En este texto efectuamos un análisis de medios sobre la llamada patente de la panela, la cual tomamos como un caso de estudio dentro de la comunicación pública de la ciencia y la tecnología. Para esto, analizamos una entrevista radial y artículos publicados en medios digitales, presentamos la trayectoria histórica que explica el interés mediático colombiano por esta solicitud de patente y estudiamos las aseveraciones realizadas por los involucrados, para establecer ciertas relaciones y percepciones sobre la tecnología y sus consecuencias sociales. Agrupamos estas comprensiones del cambio tecnológico en dos formas retóricas: la primera identifica y resalta un beneficio para la salud humana con un potencial comercial importante y la segunda presenta el caso como una privatización y demarcación de un conocimiento tradicional mediante la patente, lo que representa un peligro para los productores nacionales de panela. Exponemos los paralelos y diferencias con anteriores estudios que han descrito el involucramiento del público para buscar el cierre de la controversia con resultados que favorecen a un conjunto de actores específico. Finalmente, presentamos una postura al respecto de los elementos de estas retóricas y argumentos que deben incorporarse para que haya debates cruciales sobre tecnologías apropiadas y apropiables en Colombia.
The experiences of patients with oesophageal cancer receiving chemoradiotherapy treatment: a qualitative study embedded in the SCOPE2 trial
Authors: Holland-Hart Daniella , Longo Mirella , Bridges Sarah , Nixon Lisette Sheena , Hawkins Maria , Crosby Tom , Nelson Annmarie
Published: September 2024

Objectives

This qualitative study explored patients’ experiences and perceptions of the SCOPE2 trial. SCOPE2 examined radiotherapy dose escalation in patients with inoperable oesophageal cancer treated with definitive chemoradiotherapy (dCRT).

Setting

Recruitment at five clinical sites in England and Wales, UK.

Participants

SCOPE2 trial participants were invited to take part in interviews from across five clinical sites. Participants self-selected to take part in up to three interviews across four different time points: baseline (before treatment) and at 2–3 months, 3–6 months or 6 months+ after baseline. There were five female and five male interview participants.

Interventions

Participants were randomised to standard dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine, or an escalated dose dCRT prescribed carboplatin/paclitaxel or cisplatin/capecitabine.

Methods

This qualitative study used semistructured longitudinal interviews to explore the impact of treatment on patient outlook and quality of life and the impact of the COVID-19 pandemic. Interview data were thematically analysed.

Results

10 patients participated in 16 longitudinal interviews. Three participants were accompanied by companions. Participants experienced side-effects from radiotherapy and chemotherapy including nausea, throat pain, difficulties eating and regaining appetite, thrombosis and fatigue, although most of these symptoms gradually improved. Participants required more ongoing information and support regarding treatment side-effects and cancer status in order to improve their overall quality of life. Best practice examples involved key contacts providing practical advice and signposting support.

Conclusion

Participants of the SCOPE2 trial reported short and longer-term side-effects from chemoradiotherapy, but these usually lessened over time. Participants attempted to be positive about their survival prospects by readjusting their expectations, priorities and lifestyles. Providing patients with ongoing opportunities to discuss detailed and timely information regarding treatment side-effects, aftercare and cancer status could improve the overall health and well-being of patients during oesophageal cancer trials and pathways.

Trial registration number

NCT02741856; ISRCTN: 97125464.
Latin American Surgical Outcomes Study in Paediatrics (LASOS-Peds): study protocol and statistical analysis plan for a multicentre international observational cohort study
Authors: Quintão Vinícius Caldeira , de Sousa Gabriel Soares , Torborg Alexandra , Vieira Alexandra , Consonni Francesco , Rodrigues Samuel , Proença Julia , Carlos Ricardo Vieira , Clemente Marcella , Alonso Nivaldo , Neville Mariana , Leite Fernanda , Tonello Cristiano , Evans Faye , Garcia-Marcinkiewicz Annery , Guris Rodrigo , Herrera Jose , Andersen Ana , Schaigorodsky Lorena , Biondini Nanci , Cajas Ninón , Cruzat Francisco , Cortínez Luis Ignacio , Giraldo Marisol , Valle Alioth , Pozo Cristian , Betancourt Ana , Echeto Maria Alejandra , Dominguez Alma , Sarmiento Lina , González Kenya , Ábrego Gesely , Leguizamón Lorena , Paula Leila , Lauber Clarisa , Lopez Gabriela , Biccard Bruce M , Carmona Maria José , Hajjar Ludhmila Abrahão
Published: September 2024

Introduction

Surgery is a cost-effective public health intervention. Access to safe surgery is a basic human right. However, there are still significant disparities in the access to and safety of surgical and anaesthesia care between low-income and middle-income countries and high-income countries. The Latin American Surgical Outcomes Study in Paediatrics (LASOS-Peds) is an international, observational, 14-day cohort study to investigate the incidence of 30-day in-hospital complications following elective or emergency paediatric surgery in Latin American countries.

Methods and analysis

LASOS-Peds is a prospective, international, multicentre observational study of paediatric patients undergoing both elective and non-elective surgeries and procedures, inpatient and outpatient, including those performed outside the operating room. The primary outcome is the incidence of in-hospital postoperative complications up to 30 days after surgery. Secondary outcomes include intraoperative complications and the need for intensive care unit admission.

Ethics and dissemination

This study received approval from the Institutional Review Board of the coordinating centre (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo) as well as from all the participating centres. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences.

Trial registration number

NCT05934682.
Patients’ perspectives on ethical principles to fairly allocate scarce surgical resources during the COVID-19 pandemic in the Netherlands: a Q-methodology study
Authors: van Alphen Anouk , Lekkerkerker Caroline , Exel Job van , Baatenburg de Jong Rob , Ahaus Kees
Published: September 2024

Objectives

During the COVID-19 pandemic, healthcare professionals were faced with prioritisation dilemmas due to limited surgical capacity. While the views of healthcare professionals on fair allocation have been given considerable attention, the views of patients have been overlooked. To address this imbalance, our study aimed to identify which ethical principles are most supported by patients regarding the fair allocation of surgical resources.

Design

A Q-methodology study was conducted. Participants ranked ordered 20 statements covering different viewpoints on fair allocation according to their point of view, followed by an interview. Principal component analysis followed by varimax rotation was used to identify subgroups who broadly agreed in terms of their rankings.

Setting

The setting of this study was in the Netherlands.

Participants

16 patient representatives were purposively sampled.

Results

Two perspectives were identified, both of which supported utilitarianism. In perspective 1, labelled as ‘clinical needs and outcomes’, resource allocation should aim to maximise the health gains based on individual patient characteristics. In perspective 2, labelled as ‘population outcomes and contribution to society’, allocation should maximise health gains as with perspective 1, but this should also consider societal gains.

Conclusions

There was a broad agreement among patient representatives that utilitarianism should be the guiding ethical principle for fair allocation of scarce surgical resources. The insights gained from this study should be integrated into policymaking and prioritisation strategies in future healthcare crises.
Assessment of radiological capacity and disparities in TB diagnosis: a comparative study of Mozambique, South Africa and Spain
Authors: Munyangaju Isabelle , José Benedita , Bassat Quique , Esmail Ridwaan , Tlhapi Liebe Hendrietta , Maphophe Mqondisi , Mutemba Crimenia , Cossa Loide , Perez Patricia , Palmer Megan , Mudaly Vanessa , Carruana Eliseo Vañó , Pitcher Richard D , Lopez Varela Elisa , Thierry-Chef Isabelle
Published: September 2024

Background

Tuberculosis (TB) remains a significant global health challenge, particularly in children, where diagnosis is challenging. Radiological resources such as chest X-rays and CT scans play a crucial role in early screening and diagnosis, especially in the absence of microbiological confirmation of disease. However, radiological capacity and access vary widely across regions and countries.

Methods

This study retrospectively audited licensed X-ray and CT units in Mozambique, South Africa and Spain in 2022. Population data were used to calculate units per million people. The study used choropleth maps to visualise regional disparities and to explore potential interactions between radiological capacity, population density and TB notifications.

Results

Mozambique had the lowest radiological capacity, with 3.6 X-ray units and 0.4 CT units per million people, compared with South Africa’s 34.2 X-ray units, 5.8 CT units and Spain’s 811.5 X-ray units and 19.3 CT units. The private sector exhibited higher capacity than the public sector in all countries. Regional disparities were evident, particularly in Mozambique, highlighting urban–rural discrepancies and in-country inequalities.

Conclusion

This study underscores significant disparities in radiological capacity between low-income, middle-income and high-income countries, with economic factors playing a pivotal role. Addressing these disparities is crucial for improving TB and other disease diagnostic capabilities, particularly in resource-limited settings. Potential solutions include establishing dedicated national radio-diagnostic departments, developing national guidelines and integrating portable AI-powered X-ray or point-of-care ultrasonography technology. These findings provide valuable insights for policymakers and stakeholders to advocate for improved radiological resources and equitable healthcare access.
A Novel Approach for Sentiment Analysis of a Low Resource Language Using Deep Learning Models
Authors: Ahmed Naeem , Amin Rashid , Aldabbas Hamza , Saeed Muhammad , Bilal Muhammad , Song Houbing
Published: September 2024

Sentiment analysis is a process of dealing with people's opinions, remarks, and comments to extract valuable insights from them. Sentiment analysis can be used for various purposes like market analysis, campaign monitoring, decision-making, etc. In recent years, there has been much research on sentiment classification, particularly in English. However, these existing approaches used for the English language cannot be applied to the Urdu language. The substantial rise in communication traffic, including audio, text, video, and pictures, has significantly shifted the Internet of Things (IoT) from scalar to Multimedia Internet of Things (MIoT). So far, the integration of MIoT and NLP systems has received less attention, but it has evolved as a novel research paradigm for smart applications. This article proposes deep learning techniques for sentence-level Urdu sentiment analysis (Urdu SA) for MIoT. Our approach consists of various phases, i.e., data gathering, text preprocessing, model training, testing, and evaluation. A data set of 25 thousand Urdu reviews are used for training the proposed models. This data set is built by scraping various Urdu blogs and social media platforms, and some part of the IMDB data set is used after translating it into the Urdu language. Native Urdu speakers do data annotation, and various preprocessing techniques, i.e., tokenization, stemming, etc., are applied. The two deep learning models, i.e., Convolutional Neural Network (CNN) and Long Short-term Memory (LSTM), are trained on preprocessed Urdu reviews to find their sentiments in this article. Both models are tested using various combinations of hyperparameters, and each model's accuracy and F1 scores are evaluated. The study results show that the LSTM model outperforms the CNN model by achieving a 96% accuracy and 91% F1 score.
Exploring the Effect of Sn Doping on the Optical and Dielectric Characteristics of Nano ZnMn2−xSnxO4 Samples
Authors: Heiba Zein K. , Ghannam M. M. , Ali Essam E. , Badawi Ali , Arafat Shadia W. , Sanad Moustafa M. S. , Meselhy Neama K. , Mohamed Mohamed Bakr
Published: September 2024

ZnMn2−xSnxO4 specimens with x = 0.0, 0.03, 0.05, 0.07, 0.1 and 0.2 were obtained utilizing the sol-gel method. Rietveld refinement was employed to explore modifications in structural and microstructural features of the specimens upon Sn doping. Utilizing the SEM/EDS technique, the morphology and composition of the specimens were inspected. Inclusion of Sn ions into the ZnMn2O4 (ZMO) lattice was evidenced by the EDS analysis and confirmed by the shift in the wavenumber of IR vibrational bands of both tetrahedral and octahedral sites. From photoluminescence (PL) measurements, the pristine ZMO specimen exhibited a peak emission at 547 nm, consistent with the bandgap value E
g = 2.42 eV, recognized as edge-to-edge emissions. PL intensity diminished upon doping with Sn up to x = 0.07, then increases by increasing (x); for x = 0.2, it exceeds the peak of pure ZMO. The sample with x = 0.2 exhibited the ultimate dielectric and the greatest conductivity among other doped samples. The electrical conductivity of pure ZMO and samples with x = 0.1 adhered to the CBH model. Samples with x = 0.05 and 0.07 were characterized by the occurrence of both SP and CBH models. A sample with x = 0.2 demonstrated OLPT mechanism. The influence of the amount of Sn and temperature on the complex impedance and electric modulus were explored. All samples demonstrated a semiconductor feature except the sample with x = 0.07, which has metallic characteristics.
Use of Plackett–Burman Statistical Design to Study Factors Acting on the Nitric Acid Leaching of Rare Earth Elements from Moroccan Phosphogypsum
Authors: Asafar Fatima , Amine Marouane , Outzourhit Abdelkader , Bilali Latifa , Nadifiyine Mehdi
Published: September 2024

This work is an attempt to understand and optimize the rare earth elements leaching from Moroccan phosphogypsum using a nitric acid solution. The Plackett–Burman statistical design was used to identify the statistically significant factors responsible for the optimum leaching conditions. With this purpose, the following seven variables were studied: nitric acid concentration (X1), solid‐to‐liquid ratio (X2), temperature (X3), leaching time (X4), stirring speed (X5), drying (X6), and particle size (X7). Given that the leaching recovery of rare earth elements is limited by the quantity of dissolved phosphogypsum, we examined two simultaneous responses, namely, the leaching efficiency of rare earth elements YREEs and the leaching efficiency of calcium YCa (dissolution rate of phosphogypsum). The predicted values of the two fitted models were in good agreement with the experimental values by a coefficient of determination (R2) equal to 98.6% and 96.50%, respectively. In the model of YREEs, only the effect of drying was found to be statistically insignificant with a p‐value greater than 0.05. Nitric acid concentration, solid‐to‐liquid ratio, and temperature are the only variables having a statistically significant effect in the model of YCa. At a dissolution rate of phosphogypsum equal to 30.13%, the leaching efficiency of rare earth elements from our sample has reached a maximum of 87.55%. The optimal experimental conditions are a nitric acid concentration of 3.3 M, a solid‐to‐liquid ratio of 1/9, a temperature of 75°C, a leaching time of 20 min, a stirring speed of 200 rpm, and d ≤ 100 µm as a particle size.
Helmet Ventilation in a Child with COVID‐19 and Acute Respiratory Distress Syndrome
Authors: Chao Ke-Yun , Chen Chao-Yu , Ji Xiao-Ru , Mu Shu-Chi , Chien Yu-Hsuan
Published: September 2024

Background. In pediatric patients with severe COVID‐19, if the respiratory support provided using high‐flow nasal cannula (HFNC) becomes insufficient, no definitive evidence exists to support the escalation to noninvasive ventilation (NIV) or mechanical ventilation (MV). Case Presentation. A 9‐year‐old boy being treated with face mask‐delivered biphasic positive airway pressure ventilation developed fever, tachypnea, and frequent desaturation. The COVID‐19 polymerase chain reaction test and urine antigen test for Streptococcus pneumoniae were both positive, and sputum culture yielded Pseudomonas aeruginosa. The do‐not‐resuscitate order precluded the use of endotracheal intubation. After 2 h of HFNC support, the respiratory rate oxygenation (ROX) index declined from 7.86 to 3.71, indicating impending HFNC failure. A helmet was used to deliver NIV, and SpO2 was maintained at >90%. Dyspnea and desaturation gradually improved, and the patient was switched to HFNC 6 days later and discharged 10 days later. Conclusion. In some cases, acute respiratory distress syndrome severity cannot be measured using the oxygenation index or oxygenation saturation index, and the SpO2/FiO2 ratio and ROX index may serve as useful alternatives. Although NIV delivered through a facemask or HFNC is more popular than helmet‐delivered NIV, in certain circumstances, it can help escalate respiratory support while providing adequate protection to healthcare professionals.
Phenotypic and Genotypic Identification of Antimicrobial Resistance amongst the Campylobacter jejuni and Campylobacter coli Strains Isolated from Raw Milk of Animal Species
Authors: Banisharif Dehkordi Gholamreza , Marhamatizadeh Mohammad Hossein , Momtaz Hassan
Published: September 2024

Campylobacter jejuni and Campylobacter coli portion as an important food‐borne pathogen owing to the consumption of raw milk of animal species is unmoving unidentified. This survey appraised both phenotypic and genotypic patterns of antimicrobial resistance amongst the C. jejuni and C. coli strains isolated from raw milk samples. Totally, 850 raw milk samples were examined for C. jejuni and C. coli. After culture, species identification was done using PCR. Phenotypic and genotypic patterns of antimicrobial resistance were assessed using disk diffusion and PCR, respectively. One hundred and ten out of 850 (12.94%) raw milk samples were contaminated with Campylobacter spp (95% confidence interval). The highest contamination rate with Campylobacter spp. was observed in raw cow milk (18.18%). C. jejuni and C. coli species were detected in 45.45% and 32.72% of Campylobacter isolates, respectively (P < 0.05). C. jejuni strains showed the highest resistance rate toward tetracycline (84%), gentamicin (80%), ampicillin (74%), and erythromycin (64%). Similarly, C. coli isolates showed the highest resistance rate toward tetracycline (63.88%), gentamicin (58.33%), and ampicillin (52.77%). The lowest resistance rate of C. jejuni and C. coli was observed against chloramphenicol (10% and 2.77%), nalidixic acid (22% and 8.33%), clindamycin (36% and 13.88%), and ciprofloxacin (38% and 16.66%), respectively. The most routinely identified antimicrobial resistance genes amongst the C. jejuni isolates were tetA (66%), blaOXA−61 (54%), tetO (46%), and tetB (40%), while those of C. coli isolates were blaOXA−61 (52.77%), tetA (41.66%), cmeA (27.77%), and tetO (27.77%). The prevalence of simultaneous resistance toward more than 4 antimicrobial agents amongst the C. jejuni and C. coli isolates was 46% and 16.66%, respectively. C. jejuni and C. coli average multiple antimicrobial resistance (MAR)‐indexes in the present research were 0.49 and 0.32, respectively. The simultaneous presence of phenotypic and genotypic profiles of antimicrobial resistance amongst the resistant C. jejuni and C. coli bacteria suggests an imperative threat rendering contaminated raw milk consumption and probable occurrence of campylobacteriosis.
Supplementary Table 5 from Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen
Authors: Drabison Thomas , Boeckman Mike , Yang Yan , Huang Kevin M. , de Bruijn Peter , Nepal Mahesh R. , Silvaroli Josie A. , Chowdhury Anika T. , Eisenmann Eric D. , Cheng Xiaolin , Pabla Navjotsingh , Mathijssen Ron H.J. , Baker Sharyn D. , Hu Shuiying , Sparreboom Alex , Talebi Zahra
Published: September 2024

Table S5. PK Parameters
Table S5 from Clinical Efficacy of the HIV Protease Inhibitor Indinavir in Combination with Chemotherapy for Advanced Classic Kaposi Sarcoma Treatment: A Single-Arm, Phase II Trial in the Elderly
Authors: Sgadari Cecilia , Scoppio Biancamaria , Picconi Orietta , Tripiciano Antonella , Gaiani Francesca Maria , Francavilla Vittorio , Arancio Angela , Campagna Massimo , Palladino Clelia , Moretti Sonia , Monini Paolo , Brambilla Lucia , Ensoli Barbara
Published: September 2024

Supplementary Table 5 summarizes the representativeness of study participants
Table S1 from Clinical Efficacy of the HIV Protease Inhibitor Indinavir in Combination with Chemotherapy for Advanced Classic Kaposi Sarcoma Treatment: A Single-Arm, Phase II Trial in the Elderly
Authors: Sgadari Cecilia , Scoppio Biancamaria , Picconi Orietta , Tripiciano Antonella , Gaiani Francesca Maria , Francavilla Vittorio , Arancio Angela , Campagna Massimo , Palladino Clelia , Moretti Sonia , Monini Paolo , Brambilla Lucia , Ensoli Barbara
Published: September 2024

Supplementary Table 1 shows the active concurrent illnesses at baseline.
Supplementary Data from Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen
Authors: Drabison Thomas , Boeckman Mike , Yang Yan , Huang Kevin M. , de Bruijn Peter , Nepal Mahesh R. , Silvaroli Josie A. , Chowdhury Anika T. , Eisenmann Eric D. , Cheng Xiaolin , Pabla Navjotsingh , Mathijssen Ron H.J. , Baker Sharyn D. , Hu Shuiying , Sparreboom Alex , Talebi Zahra
Published: September 2024

SI Text and Figure Legends
Figure 3 from Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen
Authors: Drabison Thomas , Boeckman Mike , Yang Yan , Huang Kevin M. , de Bruijn Peter , Nepal Mahesh R. , Silvaroli Josie A. , Chowdhury Anika T. , Eisenmann Eric D. , Cheng Xiaolin , Pabla Navjotsingh , Mathijssen Ron H.J. , Baker Sharyn D. , Hu Shuiying , Sparreboom Alex , Talebi Zahra
Published: September 2024

Pharmacokinetics, tissue accumulation, and serum chemistry following pazopanib administration. A, Liver accumulation of pazopanib in WT (blue) or OATP1A/1B-KO mice (red) normalized to the plasma concentration of pazopanib at 24 hours (n = 5; error bars represent SD; ***, P < 0.001). B, Mean plasma concentration time profile of pazopanib in WT (blue) or OATP1A/1B-KO mice (red) after oral administration of pazopanib at a dose of 300 mg/kg (n = 5 technical replicates; error bars represent SD). C, Serum levels of AST and ALT 24 hours after a single 300 mg/kg oral dose of pazopanib in WT (blue) or OATP1A/1B-KO mice (red; n = 4; error bars represent SD; *, P < 0.05).
Table S1 from A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors
Authors: Vernet Rémi , Fernandez Eugenio , Migliorini Denis , Ancrenaz Virginie , Charrier Emily , Belkouch Marie-Claude , Von Rohr Olivier , Urwyler Muriel , De Vito Claudio , Renaux Jessica , Villard Jean , Rubin Olivier , Grogg Julien , Mach Nicolas
Published: September 2024

Representativeness of Study Participants
Figure S7 from BRCA Status Dictates Wnt Responsiveness in Epithelial Ovarian Cancer
Authors: Chehade Hussein , Gogoi Radhika , Adzibolosu Nicholas K. , Galoforo Sandra , Fehmi Rouba-Ali , Kheil Mira , Fox Alexandra , Kim Seongho , Rattan Ramandeep , Hou Zhanjun , Morris Robert T. , Matherly Larry H. , Mor Gil , Alvero Ayesha B.
Published: September 2024

qPCR analysis for Wnt3A and Ctnnb1 in ID8 mouse ovarian cancer cells. Data are presented as mean +/- SEM (n=3). Ordinary one-way ANOVA was used to calculate statistical significance.
Figure S6 from BRCA Status Dictates Wnt Responsiveness in Epithelial Ovarian Cancer
Authors: Chehade Hussein , Gogoi Radhika , Adzibolosu Nicholas K. , Galoforo Sandra , Fehmi Rouba-Ali , Kheil Mira , Fox Alexandra , Kim Seongho , Rattan Ramandeep , Hou Zhanjun , Morris Robert T. , Matherly Larry H. , Mor Gil , Alvero Ayesha B.
Published: September 2024

Nuclear and cytoplasmic green fluorescence were measured in all cells from cultures represented in Figure 3C using image J. Nuclear (left panel) and cytoplasmic (right panel) quantifications are reported separately for each cell line. Statistical significance between control and treated cultures was not achieved.
Figure S3 from Development and Application of Genetic Ancestry Reconstruction Methods to Study Diversity of Patient-Derived Models in the NCI PDXNet Consortium
Authors: Lott Paul C. , Chiu Katherine , Quino Juanita Elizabeth , Vang April Pangia , Lloyd Michael W. , Srivastava Anuj , Chuang Jeffrey H. , Carvajal-Carmona Luis G.
Published: September 2024

Figure S3 Shows the Power to detect a driver mutation that is absent in EUR but present in a non-EUR category at varying low frequencies.
Figure S2 from Development and Application of Genetic Ancestry Reconstruction Methods to Study Diversity of Patient-Derived Models in the NCI PDXNet Consortium
Authors: Lott Paul C. , Chiu Katherine , Quino Juanita Elizabeth , Vang April Pangia , Lloyd Michael W. , Srivastava Anuj , Chuang Jeffrey H. , Carvajal-Carmona Luis G.
Published: September 2024

Figure S2 shows Diversity of genetic ancestry estimates from PDXNet breast cancer models. A: Inferred genetic ancestry for 115 breast cancer models in PDXnet. B: Top two categories for 26 "MIXED" samp
Figure S1 from Development and Application of Genetic Ancestry Reconstruction Methods to Study Diversity of Patient-Derived Models in the NCI PDXNet Consortium
Authors: Lott Paul C. , Chiu Katherine , Quino Juanita Elizabeth , Vang April Pangia , Lloyd Michael W. , Srivastava Anuj , Chuang Jeffrey H. , Carvajal-Carmona Luis G.
Published: September 2024

Figure S1 shows the Clustering of 1,990 non-admixed reference samples and 2,387 admixed samples(brown) individuals based on the first three principal components. Colors represent the continental ances
Data from Clinical Efficacy of the HIV Protease Inhibitor Indinavir in Combination with Chemotherapy for Advanced Classic Kaposi Sarcoma Treatment: A Single-Arm, Phase II Trial in the Elderly
Authors: Sgadari Cecilia , Scoppio Biancamaria , Picconi Orietta , Tripiciano Antonella , Gaiani Francesca Maria , Francavilla Vittorio , Arancio Angela , Campagna Massimo , Palladino Clelia , Moretti Sonia , Monini Paolo , Brambilla Lucia , Ensoli Barbara
Published: September 2024

Abstract
Kaposi sarcoma is a rare angioproliferative disease associated with human herpes virus-8 (HHV-8) infection. Kaposi sarcoma is frequent and aggressive in HIV-infected people, whereas the classic form (CKS) generally has an indolent course. Notably, all conventional therapies against Kaposi sarcoma have only temporary efficacy. We have previously shown that indinavir, a HIV protease-inhibitor with direct antiangiogenic and antitumor activity, is safe and effective in patients with early CKS, whereas effects are less prominent in advanced disease, probably due to the larger tumor mass. Therefore, the clinical response to indinavir was assessed in patients with advanced CKS after debulking chemotherapy. This was a monocentric phase 2 trial in elderly with progressive/advanced CKS treated with debulking chemotherapy and indinavir combined, followed by a maintenance phase with indinavir alone. Secondary endpoints included safety and Kaposi sarcoma biomarker evaluation.

All evaluable patients (22) responded to debulking therapy. Out of these, 16 entered the indinavir maintenance phase. The overall response rate at end of maintenance was 75% (estimated median response-duration 43 months). Moreover, most responders showed further clinical improvements (lesion number/nodularity) during maintenance and post-treatment follow-up. Notably, after relapse, progressors did not require systemic Kaposi sarcoma therapy and showed clinical improvements (including disease stabilization) remaining on study. Responders also showed immune status amelioration with a consistent B-cell increase and positive changes of other biomarkers, including anti-HHV-8 natural killer activity. In advanced CKS a strategy combining indinavir and chemotherapy is safe and associated with high and durable response rates and it could be rapidly adopted for the clinical management of these patients.
Significance:
This phase-2 trial showed that the HIV protease inhibitor indinavir may boost and extend the duration of the effects of chemotherapy in elderly with advanced progressive classic Kaposi sarcoma, without additional toxicity. Further, the amelioration of the immune status seen in responders suggests a better control of HHV-8 infection and tumor-cell killing. Thus, indinavir combined with chemotherapy may represent an important tool for the clinical management of classic Kaposi sarcoma in elderly patients.
Data from Systematic Evaluation of Tyrosine Kinase Inhibitors as OATP1B1 Substrates Using a Competitive Counterflow Screen
Authors: Drabison Thomas , Boeckman Mike , Yang Yan , Huang Kevin M. , de Bruijn Peter , Nepal Mahesh R. , Silvaroli Josie A. , Chowdhury Anika T. , Eisenmann Eric D. , Cheng Xiaolin , Pabla Navjotsingh , Mathijssen Ron H.J. , Baker Sharyn D. , Hu Shuiying , Sparreboom Alex , Talebi Zahra
Published: September 2024

Abstract
Although the primary elimination pathway for most tyrosine kinase inhibitors (TKI) involves CYP3A4-mediated metabolism, the mechanism by which these agents are brought into hepatocytes remains unclear. In this study, we optimized and validated a competitive counterflow (CCF) assay to examine TKIs as substrates of the hepatic uptake transporter OATP1B1. The CCF method was based on the stimulated efflux of radiolabeled estradiol-17β-glucuronide under steady-state conditions in HEK293 cells engineered to overexpress OATP1B1. Of the 62 approved TKIs examined, 13 agents were identified as putative substrates of OATP1B1, and pazopanib was selected as a representative hit for further validation studies. The transport of pazopanib by OATP1B1 was confirmed by decreased activity of its target VEGFR2 in OATP1B1-overexpressing cells, but not cells lacking OATP1B1, consistent with molecular docking analyses indicating an overlapping binding orientation on OATP1B1 with the known substrate estrone-3-sulfate. In addition, the liver-to-plasma ratio of pazopanib in vivo was decreased in mice with a deficiency of the orthologous transporters, and this was accompanied by diminished pazopanib-induced hepatotoxicity, as determined by changes in the levels of liver transaminases. Our study supports the utility of CCF assays to assess substrate affinity for OATP1B1 within a large set of agents in the class of TKIs and sheds light on the mechanism by which these agents are taken up into hepatocytes in advance of metabolism.
Significance:
Despite the established exposure–pharmacodynamic relationships for many TKIs, the mechanisms underlying the agents’ unpredictable pharmacokinetic profiles remain poorly understood. We report here that the disposition of many TKIs depends on hepatic transport by OATP1B1, a process that has toxicologic ramifications for agents that are associated with hepatotoxicity.
Blocking Tryptophan Catabolism Reduces Triple-Negative Breast Cancer Invasive Capacity
Authors: Kuo Li-Wei , Crump Lyndsey S. , O’Neill Kathleen , Williams Michelle M. , Christenson Jessica L. , Spoelstra Nicole S. , Roy Micaela Kalani , Argabright Amy , Reisz Julie A. , D’Alessandro Angelo , Boorgula Meher P. , Goodspeed Andrew , Bickerdike Mike , Bitler Benjamin G. , Richer Jennifer K.
Published: September 2024

Anchorage-independent triple-negative breast cancer (TNBC) cells exhibit elevated levels of the tryptophan (TRP)-catabolizing enzyme tryptophan 2,3-dioxygenase 2 (TDO2) compared with the same cells grown under two-dimensional culture conditions. Tracing of 13C11-TRP demonstrated that anchorage-independent culture and/or inflammatory cytokines that activate NF-κB increase TRP catabolism and production of downstream catabolites such as kynurenine, which activate the aryl hydrocarbon receptor (AhR). TDO2 expression is heterogeneous within TNBC cell lines. To determine the function of TDO2, both pharmacologic inhibition and genetic manipulation were conducted. TDO2 knockdown revealed a compensatory increase in indoleamine 2,3-dioxygenase 1 (IDO1), a nonhomologous TRP-catabolizing enzyme, indicating that dual inhibition of these two enzymes is necessary to reliably block TRP catabolism. Thus, we tested a newly developed TDO2/IDO1 dual inhibitor, AT-0174, and found that it effectively inhibits TNBC TRP catabolism. Furthermore, AT-0174 treatment or AhR inhibitor significantly decreased TNBC anchorage-independent survival, invasive capacity, and expression of mesenchymal genes and proteins, whereas exogenous kynurenine increased invasion through AhR-mediated zinc finger E-box–binding homeobox 1 (ZEB1) expression. Thus, dual inhibition of TDO2/IDO1 may prove efficacious against TNBC progression.

Significance:

TDO2 is more highly expressed than the nonhomologous TRP-catabolizing enzyme IDO1 in TNBC. We find that TDO2 knockdown can lead to a compensatory increase in IDO1. Therefore, we tested a newly developed TDO2/IDO1 dual inhibitor and found that it decreases TRP catabolism, anchorage-independent survival, and invasive capacity.