bluuebunny/crossref_metadata_2025 huggingface dataset:
Повышение достоверности моделирования взаимовлияния скважин для анализа эффективности системы заводнения
Authors: Тырсин Александр Николаевич , Tyrsin Alexander Nikolayevich , Степанов Сергей Викторович , Stepanov Sergei Viktorovich , Ручкин Александр Альфредович , Ruchkin Aleksandr Al'fredovich , Бекман Александр Дмитриевич , Baeckmann Aleksandr Dmitrievich
Published: June 2023

В настоящее время для анализа эффективности системы заводнения нефтяных месторождений активно используются прокси-модели семейства CRM (capacitance-resistive model, емкостно-резистивные модели) -- математические модели материального баланса, сформулированные в рамках электродинамической аналогии. Однако при большом количестве добывающих и нагнетательных скважин снижается
точность моделирования ввиду множества локальных минимумов целевой функции. Одной из причин подобной неоднозначности решения является отсутствие
априорной информации о том, какие нагнетательные скважины действительно оказывают влияние на ту или иную добывающую скважину. Определена маска взаимовлияния, позволившая значительно сократить число определяемых коэффициентов взаимовлияния. Предложен вычислительный алгоритм, в котором вместо многоэкстремальной задачи решается последовательность задач с квадратичной целевой функцией и выпуклыми ограничениями на переменные в форме простых неравенств. Приведен пример апробации предложенного метода.
Practice schools as third spaces? Navigating the continuum between hierarchical models and collaborative partnerships in teaching practice in South Africa
Authors: Le Roux Sarlina Gertruida , Lemmer Rina
Published: June 2023

Mentoring student teachers is a fundamental approach in teaching practice. Traditionally, teaching-practice models have been based on cognitive apprentice approaches and have been hierarchical in nature. Problems with finding suitable schools for teaching practice and mentoring experiences have been challenging, which has led to the implementation of collaborative partnership approaches. In South Africa, minimal research has been undertaken on the establishment of partnerships to strengthen teaching practice, with work in the third space almost non-existent. The research question under investigation in this paper is as follows: How do we move away from hierarchical models of teaching practice and establish collaborative partnerships between schools and universities? The paper is underpinned by both third space theory and border theory. The aim of the paper is, first, to explore the challenges encountered with the hierarchical models used in teaching practice. Second, we explore what collaborative educational partnerships entail and investigate the various models used internationally to establish partnerships between universities and schools to strengthen teaching practice. This non-empirical paper uses a secondary-source data design that draws on existing texts, research findings, and journal articles. A qualitative research approach has been employed as it allows a narrative description of the data collected. An interpretive approach is employed to interpret and to discuss the findings. The paper concludes by reviewing practice schools as a type of school that allows lecturers, teachers, and students to cross institutional borders and collaborate in the third space.
Inclusivity and the remote doctorate supervision experience of a student with disability in a South African university
Authors: Akala Benard
Published: June 2023

These are personal accounts blended with literature on higher education in South Africa that reveal my experiences as a patient and a disabled online doctoral student. In recovery, I encountered challenges in reading, walking, speaking, and swallowing. Using the narrative technique, this article highlights the academic challenges that I experienced as I transformed into a disabled online doctoral student. To demonstrate the strength of habitus as espoused, the faculty of education demanded an abeyance letter explaining the delay in my doctoral studies. The paper reveals delays in receiving feedback, lack of physical, and intellectual feedback from PhD colleagues and my experience of the burden of critical thinking about doctoral studies.  The paper recommends that the Department of education along with higher education institutions should spell out what should be done when a higher education student(s) develops disability(ies)while enrolled and the extent to which they can be included in institutions of higher learning.
Implementación y gestión de un sistema de costos del hostal “Plan b” en el distrito de Lurigancho Chosica 2022
Authors:   , Aranguren Crespo Juan Diego , Quiñones Arroyo Jeancarlos Diodoro , Quispe Mamani Lidia Consuelo
Published: June 2023

La presente tesis, busca la implementación de un sistema de costos y poder gestionar con mayor efectividad el sistema de costos y poder mejorar el proceso del control productivo que ofrecen el servicio de hotelería obteniendo una mejor rentabilidad para su medición del costo estándar a su vez poder gestionar esta medida para ser más precisos y que permita a la gerencia tomar unas mejores decisiones en los servicios de alojamiento en el hostal de Lurigancho Chosica. También mencionaremos que los servicios de hotelería no cuentan con un método de costos propios de esta manera no se ha podido realizar una adecuada distribución de costos usados al servicio de alojamiento, se analizará los costos estándares y se determina el precio venta exacto y precisar la rentabilidad este método se aplicará a los costos permitiendo poder gestionar y determinando su efectividad el precioindividual del servicio del Hostalpues ofrece y brinda a los usuarios también para conocer la utilidad real del hostal de Lurigancho Chosica.
Correlación entre el nivel de conocimiento sobre nutrición y nivel de calidad de vida de los pacientes de dos centros de hemodiálisis de Lima - 2021
Authors:   , Espinoza Wong Sazkia Paola , Ramos Mendoza Heylin Nickole
Published: June 2023

Introducción: La Enfermedad Renal Crónica (ERC) constituye un problema de salud pública por su alta prevalencia, alto costo asociado al tratamiento, los desequilibrios metabólicos asociados a una mala nutrición y el impacto que tiene sobre la calidad de vida. Objetivo: Determinar la correlación entre el nivel de conocimiento sobre nutrición y la calidad de vida de los pacientes de dos Centros de Hemodiálisis. Materiales y métodos: Es un estudio observacional, analítico y transversal. En una muestra de 116 personas de ambos sexos, se realizaron encuestas de conocimiento en nutrición y calidad de vida. Para evaluar la correlación, se utilizó la prueba de Spearman y además, se realizó un análisis de regresión lineal para evaluar la magnitud de asociación entre las variables. Resultados: A través del análisis estadístico se encontró que el promedio del puntaje EuroQol-5D (EQ-5D) fue significativamente mayor en participantes con alto conocimiento nutricional. Adicionalmente, el puntaje EQ-5D fue notoriamente mayor en aquellos con grado de instrucción de secundaria completa y técnico superior. Por otro lado, las mujeres con un conocimiento más alto en nutrición tenían mayor calidad de vida. Conclusiones: Existe una correlación entre el nivel de conocimiento en nutrición y calidad de vida en pacientes hemodializados. Además, las mujeres tienen mejor calidad de vida y también, se halló una correlación positiva respecto a un mayor grado de instrucción.
Prácticas, actitudes y creencias durante la lactancia y sus factores sociodemográficos en las madres del área de CRED del Centro Materno Infantil Los Sureños, Puente Piedra - Lima Perú, 2021
Authors:   , Soto Quispe Stephany Elizabeth , Rivera Bautista Elizabeth Noemí
Published: June 2023

La lactancia materna es el medio por el cual el niño va recibir los nutrientes necesarios para su completo desarrollo, brinda los anticuerpos que lo protegerán de futuras patologías crea vínculos afectivos entre él y su madre. Además, fomenta el desarrollo cognitivo – social en el infante y pueda desenvolverse adecuadamente en sociedad. El estudio tuvo como objetivo: Determinar la asociación entre las prácticas, actitudes y creencias durante la lactancia y sus factores sociodemográficos en el área de CRED del Centro Materno Infantil Los Sureños del distrito Puente Piedra – Lima. Metodología: tipo observacional, descriptivo, transversal. Como técnica fue utilizada la encuesta y el instrumento fue el cuestionario, que estuvo dirigido a 250 madres y sus hijos menores de 2 años; las madres fueron invitadas a participar informándola sobre la importancia de la lactancia y el efecto que causa en el desarrollo de su menor hijo, además se les mencionó el anonimato de sus respuestas. Asimismo, el proceso estadístico se realizó a través de chi cuadrado. Resultados: Se encontró prevalencia del grupo etario de 25 a 34 años (45,6%), grado de instrucción secundaria (77,2%) y ocupación ama de casa (47,6%). Se evidenció que existe relación entre la práctica y el factor sociodemográfico grado de instrucción (p=0,001). La actitud se asoció con la edad (p=0,042) y el grado de instrucción (p=0,008). Las creencias se asociaron solo con la edad (p=0,018). Conclusión: Se encontró que la práctica inadecuada estuvo asociada al grado de instrucción, la actitud se asoció a la edad y al grado de instrucción y las creencias estuvieron asociadas son con la edad. Estos hallazgos sirven para el desarrollo de estrategias preventivas más eficaces, objetivas y dirigidas a aspectos específicos que permitan el incremento de la práctica de lactancia.
Asociación entre violencia familiar durante el embarazo y el bajo peso al nacer: análisis de la Encuesta Demográfica y Salud Familiar 2019
Authors:   , Periche Medrano Laura Virginia , Guerrero Loarte Maria Alejandra
Published: June 2023

Introducción: la violencia física de pareja es un problema social y de salud pública. Las mujeres en etapa reproductiva, especialmente las embarazadas, han sufrido violencia física, asociada a consecuencias para el feto como bajo peso al nacer y aborto. Objetivo: determinar la asociación entre violencia física durante el embarazo en mujeres peruanas de 15 a 49 años con bajo peso al nacer y aborto según la Encuesta Demográfica y de Salud Familiar (ENDES) 2019. Metodología: estudio transversal analítico utilizando la información de la ENDES 2019. Se incluyeron dos variables dependientes referidas a los resultados del parto: aborto y bajo peso al nacer. La variable independiente fue la violencia física durante el embarazo por parte de su actual o anterior esposo/pareja. Se utilizaron modelos de regresión lineal generalizada de la familia Poisson con función de enlace logarítmico para determinar la asociación de interés y estimar razones de prevalencia (RP) crudas y ajustadas por las variables confusoras (características sociodemográficas, del embarazo y del parto de las mujeres) junto con sus intervalos de confianza (IC) al 95%. Resultados: un total de 15305 mujeres con un embarazo en los últimos cinco años. Se incluyeron en el estudio. El 6,43% de las participantes experimentó violencia física en la gestación. En cuanto a los desenlaces adversos del embarazo, se encontró una prevalencia de aborto y bajo peso al nacer de 20,84% y 6,01%, respectivamente. Se halló que las mujeres que sufrieron violencia física en la gestación tenían mayor probabilidad de abortar (RPa= 1,43; IC 95%: 1,24-1,64; p<0,001) pero no de tener un recién nacido con bajo peso al nacer (RPa= 0,80; IC 95% : 0,58-1,10; p= 0,174). Conclusión: se encontró que 6 de cada 100 mujeres peruanas en edad fértil experimentó violencia física...
Asociación entre la condición de discapacidad y la depresión en personas privadas de su libertad en Perú
Authors:   , Ñaupari Barboza Maria Soledad , Urquiso De La Cruz Christhian Enrique
Published: June 2023

Objetivos:Determinar la asociación entre la condición de discapacidad y la depresión en personas privadas de su libertad de Perú. Métodos: Realizamos una estudio transversal con datos secundarios del Primer Censo Nacional Penitenciario 2016 de Perú. La variable independiente fue la condición de discapacidad y la variable dependiente fue la depresión diagnosticada por un profesional de la salud, en el establecimiento penitenciario. Incluimos posibles variables de confusión. Para estimar la magnitud de la asociación principal utilizamos modelos crudos y ajustados de regresión de Poisson con varianza robusta. Los resultados se reportaron con razones de prevalencia (RP) y sus intervalos de confianza al 95% (IC95%). Resultados:El 29,9% de las personas privadas de su libertad tenía discapacidad y el 2,8% indico que padecía de depresión diagnosticada por un profesional de salud en el establecimiento penitenciario. Luego a ajustar por variables de confusión, las personas privadas de su libertad con discapacidad (leve RP=1,74 IC95%:1,55–1,96, moderada RP=2,24 IC95%: 1,99–2,53) y severa RP=2,69 IC95%: 2,35–3,09) tuvieron más probabilidad de tener depresión en comparación con las personas sin discapacidad.Conclusiones: En el Perú, en el 2016, las personas privadas de su libertad tuvieron más probabilidad de tener depresión que sus pares sin discapacidad. Asimismo, las prevalencias de depresión se incrementaron de acuerdo con los niveles de discapacidad. Es necesario que se priorice a este grupo poblacional en las políticas de salud mental penitenciarias.
An improved GM(1,1) forecasting model based on Aquila Optimizer for wind power generation in Sichuan Province
Authors: Ren Youyang , Xia Lin , Wang Yuhong
Published: June 2023

With the rapid development of China's economy, the development of wind resources has important practical significance for alleviating environmental pollution problems in various provinces and cities in China. As China's clean energy province and t western economic center, Sichuan's wind power industry is gradually starting from the 13th Five-Year Plan. Considering the volatility and periodic characteristics of wind power generation in Sichuan Province, this paper proposes an optimized seasonal grey model based on a novel algorithm (Aquila Optimizer). We use dummy variables 1 and 0 to represent seasonal factors and perform seasonal classification of the sample data. According to the classification sequence, we construct a grey prediction model with optimized initial value and background value by Aquila Optimizer. In this paper, we use this model to predict wind power generation in Sichuan Province and verify the validity and rationality of the model by comparing it with other methods. Finally, we further predicted the power generation during the 14th Five-Year Plan period to provide policy advice and planning for the future development of the clean energy industry in Sichuan Province.
Novel Chaotic Image Encryption Using Dynamic DNA Coding
Authors: Zhou Shuang , Wei Yi , Zhang Yingqian , Teng Lin
Published: June 2023

To solve the problem of a small key space of image cryptosystem based on logistic, this paper presents a new 1D chaotic map with a wider and continuous chaotic ranges, much larger Lyapunov exponent and more complex behavior. Then, a novel image cryptosystem based on the proposed map and dynamic DNA encoding is designed. Compared other DNA encoding image encryption methods, our dynamic DNA coding process is simple, easy to operate and implement with good effect. Experimental results presented that compared with the fixed DNA and recent related chaos-based image encryption schemes, the proposed cryptosystem has higher security.
Patients with Electrolyte Disturbances Can Be Safely and Effectively Treated in a Hospital-at-home, Telemedicine Controlled Environment
Authors: Segal Gad , Gueron Or , Cohn May , Zubli Daniel , Hakim Hila , Fizdel Boris , Liber Pninit , Amir Hadar , Barkai Galia
Published: June 2023

Background.
Classic morbidities in the realm of hospital-at-home (HAH) include infectious diseases and exacerbations of chronic conditions. Electrolyte disturbances are not included in the recommended primary diagnoses of HAH. However, their rate is high. The aim of this study was to describe our experience with monitoring and treatment of such patients.
Methods.
This was a retrospective analysis of patients in the setting of telemedicine-controlled HAH. We collected data from Electronic Medical Records (EMRs) and selected patients who suffered, at some point during their hospitalizations, from electrolyte disturbances.
Results.
During 14 months, we treated a total of 267 patients in the HAH settings. The mean patients’ age was 72.2 + 16.4, 44.2% were males. Overall, 261 (97.75%) patients were flagged with electrolyte disturbances. Within this group, we identified 149 cases of true electrolyte disturbances (with several patients suffering from more than one electrolyte disturbance) after normalization: 67 cases (44.96%) had hyponatremia and 9 (6.04%) had hypernatremia, after correction for hyperglycemia. 20 cases (13.42%) of hypokalemia and 27 cases (18.12%) of hyperkalemia after exclusion of hemolytic samples. 10 cases (6.09%) of hypocalcemia and 2 cases (1.34%) of hypercalcemia, both corrected to albumin blood levels. We identified 13 cases (8.72%) of hypomagnesemia and 1 case (0.67%) of hypermagnesemia. Within the group of patients suffering from electrolyte disturbances there were more patients suffering from chronic kidney disease (24.2% vs. 12.2%; p = 0.03), a larger portion of patients suffering from malignancy (6.3% vs. 0.6%; p = 0.006) and a larger portion of patients treated with diuretics (12.6% vs. 4.1%; p = 0.016). None of these patients died nor suffered from clinically significant cardiac arrhythmias.
Conclusion.
The extent of electrolyte disturbances amongst patients at the HAH setting is high. Monitoring and treatment of such patients can be done safely in this setting.
Efficacy and Safety of Naldemedine for Opioid-Induced Constipation in Older Patients with Cancer: A Retrospective Study
Authors: Imai Hisao , Fujita Yukiyoshi , Hiruta Eriko , Masuno Takashi , Yamazaki Shigeki , Tanaka Hajime , Kamiya Teruhiko , Sandoh Mitsuru , Takei Satoshi , Arai Kazuya , Nishiba Hiromi , Mogi Junnosuke , Koizuka Shiro , Saito Taeko , Obayashi Kyoko , Kaira Kyoichi , Minato Koichi
Published: June 2023

Background
Opioids are pain relievers that are often associated with opioid-induced constipation (OIC) that worsens with age. We performed a multicenter, retrospective analysis on the efficacy and safety of naldemedine, an opioid receptor antagonist, in treating OIC in patients with cancer (age > 75 years).
Methods
The electronic medical records of cancer patients who received naldemedine at 10 Japanese institutions between June 7, 2017, and August 31, 2019, were retrieved. Patients aged ≥ 75 years who were treated with naldemedine for the first time and hospitalized for at least 7 days before and after initiating naldemedine therapy were included in this analysis.
Results
The patient’s bowel movements were evaluated for at least 7 days before and after naldemedine initiation. The response rate was 68.3%, and the frequency of bowel movements increased significantly after naldemedine administration in the overall population (p < 0.0001) and among those who defecated < 3 times/week before naldemedine administration (p < 0.0001). Diarrhea was the most frequent adverse event in all grades, observed in 45% of patients, of which 92.6% were Grade 1 or 2. Grade 4 or higher adverse events, including death, were not observed.
Conclusions
Naldemedine exhibits significant efficacy and safety in OIC treatment in older patients with cancer.
Vasorelaxing effect of 6β-hydroxybetulinic acid
Authors: Carocci Antonella , Estrada Omar
Published: June 2023

Cardiovascular diseases are currently the main causes of morbidity and mortality in the world. The available medications have undesirable side effects or lose effectiveness due to pharmacological tolerance. For this reason, it is necessary to look for new molecules and therapeutic alternatives for its treatment. 6-Hydroxybetulinic acid is a triterpene isolated from the leaves of Licania cruegeriana that demonstrated a hypotensive effect in hypertensive rats. In the present work, we evaluated the vasorelaxing effect of this triterpene in rat aortic rings (ex vivo) and its possible action mechanism. 6β-hydroxybetulinic acid develops its vasorelaxing effect in a concentration-dependent manner, and not dependent on the vascular endothelium (n:6, IC50: 9.98 µM) and induced by phenylephrine or KCl in rat aortic rings in a non-competitive manner. The 6HB-induced vasorelaxation was related to the inhibition of Ca2+ inflow from the extracellular medium and the inhibition of NO/GMPc pathway. Since vascular tone is a determinant of arterial pressure in mammals, these results could partially explain the hypotensive effect demonstrated in in vivo experiments.
Interpretable statistical representations of neural population dynamics and geometry
Authors: Peach Robert , Arnaudon Alexis , Barahona Mauricio , Vandergheynst Pierre , Gosztolai Adam
Published: June 2023

The dynamics of neuron populations during diverse behaviours evolve on low-dimensional manifolds. However, it remains challenging to disentangle the role of manifold geometry and dynamics in encoding task variables. Here, we introduce an unsupervised geometric deep learning framework for representing non-linear dynamical systems based on statistical distributions of local dynamical features. Our method provides geometry-aware or geometry-agnostic representations for robustly comparing dynamical systems based on sparse measurements. Our representations are generalisable to compare computations across systems, interpretable to discover a geometric correspondence between neural dynamics and kinematics in a primate reaching task, and intrinsically encode temporal information to give rise to a decoding algorithm with state-of-the-art accuracy. Our results suggest that using the manifold structure over temporal information is important to develop better decoding algorithms and assimilate data across experiments.
Difference analysis of intestinal flora in ICU patients with different sampling methods -a systematic Review and meta-analysis
Authors: Qiu Songlin , Zheng Binyan , Pan Juan , Xu Jiufei , Yu Sufei , Qian Jiao , Wang Yilan , Shen Bo , Tung Tao-Hsin
Published: June 2023

Background
ICU patients often use swab samples instead of stool samples for subsequent analysis due to the complexity of sampling. Whether there are significant differences in the gut microbiota between the two specimen types (stool and swab) has not been determined. We performed a meta-analysis to investigate whether gut microbiota obtained by different sampling methods were altered.
Methods
A systematic review of studies published in electronic databases up to December 2022 was performed. We included 11 studies that analyzed the abundance and diversity of gut microbiota using standard deviation means and random-effects models for different sampling methods and for ICU patients and healthy cohorts
Results
After entering the ICU for treatment, the intestinal flora of the patients and the normal population were significantly different, and the diversity and richness of the flora were significantly higher than those of the healthy population. In addition, using two different sampling methods, feces and swabs, had no significant effect on the α-diversity of intestinal flora in ICU patients.
Conclusion
Our results provide a comprehensive synthesis to better understand gut microbial perturbations associated between different sampling methods, as well as differences in the microbiota between ICU patients and healthy populations.
Perception of Temporal Synchrony Not a Prerequisite for Multisensory Integration
Authors: Jertberg Robert M. , Begeer Sander , Geurts Hilde M. , Chakrabarti Bhismadev , Burg Erik Van der
Published: June 2023

Temporal alignment is often viewed as the most essential cue the brain can use to integrate information from across sensory modalities. However, the importance of conscious perception of synchrony to multisensory integration is a controversial topic. Conversely, the influence of cross-modal incongruence of higher level stimulus features such as phonetics on temporal processing is poorly understood. To explore the nuances of this relationship between temporal processing and multisensory integration, we presented 101 participants (ranging from 19 to 73 years of age) with stimuli designed to elicit the McGurk/MacDonald illusion (either matched or mismatched pairs of phonemes and visemes) with varying degrees of stimulus onset asynchrony between the visual and auditory streams. We asked them to indicate which syllable they perceived and whether the video and audio were synchronized on each trial. We found that participants often experienced the illusion despite not perceiving the stimuli as synchronous, and that the same phonetic incongruence that produced the illusion also led to significant interference in simultaneity judgments. These findings challenge the longstanding assumption that perception of synchrony is a prerequisite to multisensory integration, support a more flexible view of multisensory integration, and suggest a complex, reciprocal relationship between temporal and multisensory processing.
Effect of dietary cholesterol, phytosterol, and docosahexaenoic acid on astaxanthin absorption and retention in rainbow trout
Authors: Jin Yang , Li Keshuai , Vik Jon Olav , Hillestad Marie , Olsen Rolf Erik
Published: June 2023

Astaxanthin (Ax) determines the flesh redness of a salmonid fish which is the most desirable quality indicator by consumers. Fish cannot synthesize Ax de novo, therefore the only way to increase flesh redness is to increase dietary input or the absorption and retention rate of dietary Ax. As a hydrophobic carotenoid, the absorption of Ax can be modulated by other lipid molecules in the diet. The present study explored the effect of three lipids, cholesterol (CH), phytosterol (PS) and docosahexaenoic acid (DHA) on Ax absorption, transport, and retention in rainbow trout. Dietary CH significantly improved Ax absorption by elevating plasma Ax levels (p < 0.05), however it had no effect on whole body Ax or flesh color. Dietary PS appears to inhibit Ax absorption since fish had significantly (p < 0.05) reduced whole body Ax. Dietary DHA appeared to have no effect on Ax absorption or retention. By comparing intestinal transcriptomes, we have identified the gene low density lipoprotein receptor (ldlr) which was significantly downregulated in fish fed the cholesterol diet as compared to the control diet. Since ldlr plays a major role in plasma lipoprotein turnover, we hypothesized that the inhibition of ldlr by high dietary cholesterol resulted in higher retention of plasma astaxanthin. The elevation of plasma astaxanthin was not reflected in higher flesh coloration, which suggest other limiting factors governing astaxanthin retention in muscle. However, the transcriptomic and proteomic analyses found no changes of genes or proteins involved in Ax absorption, transport, or excretion in fish fed PS or DHA diets as compared to the control. In conclusion, our study has suggested that CH promotes Ax absorption by regulating lipoprotein retention and provide evidence for improving Ax absorption via dietary modulation.
Odonata of Wayanad Wildlife Sanctuary, Kerala State, Southern India
Authors: PK Muneer , S Narendra Babu , Chandran Vivek , Jose Subin K
Published: June 2023

A preliminary study of the odonate fauna of Wayanad Wildlife Sanctuary, Kerala, southern India was carried out from August 2020 to November 2020. Ponds, streams, and swamps in the sanctuary were sampled using Visual Encounter Surveys (VES). A total of 84 species (49 dragonflies and 35 damselflies) from 11 families were recorded, out of which 13 are endemic to the Western Ghats. Orthetrum pruinosum was found to be the most common species in the sanctuary. Indolestes pulcherrimus, an endemic species with no recent records, is being reported for the first time with photographs from the wild. The highest number of species was recorded in the ponds (56), followed by streams (46) and swamps (33). However, the number of endemic species was highest in the streams (8), followed by swamps (3) and ponds (2).
Split intein-mediated protein trans-splicing to express large dystrophins
Authors: Tasfaout Hichem , Halbert Christine , Allen James , Reyes Theodore , Grimm Dirk , Hauschka Stephen , Chamberlain Jeffrey
Published: June 2023

Gene replacement using Adeno-associated viral (AAV) vectors represents a promising approach for many diseases. However, this therapeutic modality is challenged by the modest packaging capacity of AAVs (~4.7 kb), limiting its application for disorders involving large genes, such as Duchenne muscular dystrophy with a coding sequence >11 kb. Here we developed a novel method for expressing large dystrophins by utilizing the protein trans-splicing mechanism mediated by split inteins. We identified several split intein pairs that can efficiently join two or three fragments and generate, respectively, a large midi-dystrophin or the entire full-length dystrophin. We show that the delivery of two or three AAVs into dystrophic mice results in robust expression of large dystrophins with significant functional improvements compared with current micro-dystrophins. Moreover, using the potent myotropic AAVMYO, we demonstrate that low doses (2x1013 vg/kg) are sufficient to express large dystrophins in striated muscles bodywide with significant physiological corrections in young or very old dystrophic mice. Our data support the feasibility of this approach in vivo and show a clear superiority of large dystrophins over micro-dystrophins that are being tested in clinical trials. This novel method could benefit any patient with Duchenne or Becker muscular dystrophy regardless of genotype and could be adapted to numerous other disorders caused by mutations in large genes exceeding the carrying capacity of AAV.
Common risk alleles for schizophrenia within the Major Histocompatibility Complex predict white matter microstructure
Authors: Simmonds Emily , Pardinas Antonio , Anney Richard , Legge Sophie , Walters James , Harrison Neil , O'Donovan Michael , Escott-Price Valentina , Caseras Xavier
Published: June 2023

Recent research has highlighted the role of complement genes in shaping the microstructure of the brain during early development, and in contributing to common allele risk for Schizophrenia. We hypothesised that common risk variants for schizophrenia within complement genes will associate with structural changes in white matter microstructure within tracts innervating the frontal lobe. Our results show that risk alleles within the complement gene set, but also intergenic alleles, significantly predict axonal density in these white matter tracts. More specifically, risk alleles within the Major Histocompatibility Complex (MHC) region in chromosome 6 appeared to drive these association, although intergenic alleles mostly within chromosome 19 also show to play part. No significant associations were found for the orientation dispersion index. Our results suggest changes in axonal packing - but not in axonal coherence - determined by common risk alleles within the MHC genomic region, as a potential neurobiological mechanism for schizophrenia.
Electroconvulsive therapy-induced volumetric brain changes converge on a common causal circuit in depression
Authors: Deng Zhi-De , Ousdal Olga Theresa , Oltedal Leif , Angulo Brian , Baradits Mate , Spitzberg Andrew , Kessler Ute , Sartorius Alexander , Dols Annemiek , Narr Katherine , Espinoza Randall , Waarde Jeroen Van , Tendolkar Indira , Eijndhoven Philip van , Wingen Guido van , Takamiya Akihiro , Kishimoto Taishiro , Jorgensen Martin , Jorgensen Anders , Paulson Olaf , Yrondi Antoine , Peran Patrice , Soriano-Mas Carles , Cardoner Narcís , Cano Marta , Diermen Linda van , Schrijvers Didier , Belge Jean-Baptiste , Emsell Louise , Bouckaert Filip , Vandenbulcke Mathieu , Kiebs Maximilian , Hurlemann Rene , Mulders Peter , Redlich Ronny , Dannlowski Udo , Kavakbasi Erhan , Kritzer Michael , Ellard Kristen , Camprodon Joan , Petrides Georgios , Maholtra Anil , Abbott Christopher , Argyelan Miklos
Published: June 2023

Neurostimulation is a mainstream treatment option for major depression. Neuromodulation techniques apply repetitive magnetic or electrical stimulation to some neural target but significantly differ in their invasiveness, spatial selectivity, mechanism of action, and efficacy. Despite these differences, recent analyses of transcranial magnetic stimulation (TMS) and deep brain stimulation (DBS)-treated individuals converged on a common neural network that might have a causal role in treatment response. We set out to investigate if the neuronal underpinnings of electroconvulsive therapy (ECT) are similarly associated with this common causal network (CCN). Our aim here is to provide a comprehensive analysis in three cohorts of patients segregated by electrode placement (N = 246 with right unilateral, 79 with bitemporal, and 61 with mixed) who underwent ECT. We conducted a data-driven, unsupervised multivariate neuroimaging analysis (Principal Component Analysis, PCA) of the cortical and subcortical volume changes and electric field (EF) distribution to explore changes within the CCN associated with antidepressant outcomes. Despite the different treatment modalities (ECT vs TMS and DBS) and methodological approaches (structural vs functional networks), we found a highly similar pattern of change within the CCN in the three cohorts of patients (spatial similarity across 85 regions: r = 0.65, 0.58, 0.40, df = 83). Most importantly, the expression of this pattern correlated with clinical outcomes. This evidence further supports that treatment interventions converge on a CCN in depression. Optimizing modulation of this network could serve to improve the outcome of neurostimulation in depression.
Tumor heterogeneity and prognostic impact of the aberrant splicing burden of colorectal cancers
Authors: Eilertsen Ina , Langerud Jonas , Johannessen Bjarne , Nesbakken Arild , Lothe Ragnhild , Sveen Anita
Published: June 2023

The colorectal cancer (CRC) transcriptome has important clinicopathological associations. Alternative splicing is a major determinant of transcriptomic complexity, but the impact of aberrant splicing on tumor heterogeneity and patient outcome from CRC is not well described. We investigated inter- and intra-tumor splicing heterogeneity among 504 primary tumor samples and 42 non-malignant colonic mucosa samples from 314 patients analyzed on splicing-sensitive microarrays. Most (62%) cancer-specific splicing events were rare across the tumors, and even heterogeneously expressed among multiregional samples, consistent with splicing noise. However, several novel events had high prevalence and a significant impact on the expression level of cancer-critical target genes, such as SFRP4 and RNF43. The tumor splicing burden (TSB) was identified as a main discriminatory feature of the splicing profiles of CRCs. The TSB was not driven by suspected noisy events, but correlated with gene set enrichment scores of splicing-related pathways and cell cycle progression. A high TSB was an independent predictor of a favorable 5-year relapse-free survival (multivariable hazard ratio 0.55, 95% confidence interval 0.32–0.92), and not confounded by immune cell infiltration or intra-tumor heterogeneity. This study highlights the contribution of splicing to tumor heterogeneity in CRC, and we propose the TSB as a prognostically relevant feature.
Differential roles of the medial and lateral orbitofrontal cortex in decision-making
Authors: Qiu Lixin , Qiu Yidan , Liao Jiajun , Li Jinhui , Zhang Xiaoying , Chen Kemeng , Huang Qinda , Huang Ruiwang
Published: June 2023

Inferring potential outcomes and updating behavior are prerequisites for making flexible decisions. These abilities are highly associated with the functions of the orbitofrontal cortex (OFC). Previous studies proposed that the lateral OFC (lOFC) infers the potential outcomes and the medial OFC (mOFC) encodes the general information to guide behavior. However, recent works suggested that both these two subregions responded to the same decision-related variable. Therefore, the exact roles of mOFC and lOFC in decision-making remain unclear. To study this issue, we conducted an inference-based decision-making experiment combining with functional magnetic resonance imaging techniques. Here we found that both the mOFC and lOFC represented the inferred outcomes, but only the lOFC was responsible for the outcome inference. Although the inferred outcomes were decodable in both subregions, the outcome in the mOFC was context-general coding, whereas it was context-specific in lOFC. Moreover, the functional coupling analysis showed that the mOFC may update behavior through sensory mediation and motor execution, whereas the lOFC may update behavior through task rule retrieving, alertness maintaining, and motor planning. We concluded that the OFC subregions may be collectively activated in decision-making, but their exact roles can be dissociable.
Reduction of satellite signature effect in high accuracy satellite laser ranging to Etalon
Authors: An Ning , Guan wen bo , Podesta Ricardo Cesar , Nuñez Natalia Edith , Gao Jian , dong xue , ma lei , liu zhi cheng
Published: June 2023

Etalon satellite is regarded as one of the most promising tools for studying crustal motions, Earth rotation and other scientific applications. Unfortunately, its outsized shape and signature caused an adverse satellite signature effect on its range accuracy. In this study, we use the Retroreflector Uneven Distribution Model to simulate the echo signals sent from Etalon and figure out how the value of the corresponding center of mass corrections changes according to the incident angles. A center mass of correction filter has been proposed and implemented in the standard SLR data processing to eliminate satellite signature effect from the distribution of the post-fit residuals of Etalon. The measurements with minimum variability are selected by modifying the rejection criterion of effective returns. The statistical results of our study reveal that the new algorithm has a significantly better ranging accuracy. The mean RMS of normal points has been reduced from 163.7 ± 41.8ps to 118.2 ± 8.94ps, while the stability of the collected data has been improved by 79%. In addition, the new algorithm is able to improve the range accuracy of Etalon-2 by almost identical proportions. This method seeks to minimize the range bias induced by the variations in satellite signature effect at different incident angles, which provides a theoretical reference for the research on millimetre level satellite laser ranging.
Updating approach for lexicographic optimization-based planning to improve cervical cancer plan quality
Authors: Caricato Paolo , Trivellato Sara , Pellegrini Roberto , Montanari Gianluca , Daniotti Martina Camilla , Bordigoni Bianca , Faccenda Valeria , Panizza Denis , Meregalli Sofia , Bonetto Elisa , Voet Peter , Arcangeli Stefano , Ponti Elena
Published: June 2023

Background
To investigate the capability of mCycle (Elekta AB, Stockholm, Sweden), a fully automated lexicographic-optimization planning algorithm, to enhance plan quality of an already-validated Wish-List (WL) pushing on the organs-at-risk (OAR) sparing.
Material and Methods
Twenty-four mono-institutional cervical cancer VMAT plans were retrospectively selected. Two WLs have been defined to reproduce manual plans (WL01), and to improve the OAR sparing without affecting minimum target coverage and plan delivery accuracy (WL02). These WLs were used to automatically re-plan the selected cases. Manual plans (MP) and mCycle plans (mCP01 and mCP02) were compared in terms of dose distributions, complexity, delivery accuracy, and clinical acceptability. Two senior physicians independently performed a blind clinical evaluation, and a global quality index was used for overall assessment.
Results
WL tweaking requests 5 and 3 working days for the WL01 and the WL02, respectively. The re-planning took 3 working days in both cases. mCP01 best performed in terms of target coverage (PTV V95% (%): MP 98.0 [95.6–99.3], mCP01 99.2 [89.7–99.9], mCP02 96.9 [89.4–99.5]), while mCP02 showed an OAR sparing improvement (e.g., Rectum D50% (Gy): MP 41.7 [30.2–47.0], mCP01 40.3 [31.4–45.8], mCP02 32.6 [26.9–42.6]). The complexity of mCPs increased without affecting plan delivery accuracy. In blinded comparisons, all mCPs were considered clinically acceptable, and were preferred over MP in 90% of cases. Globally, mCPs registered plan quality scores at least comparable to MP.
Conclusions
This study showed the flexibility of the lexicographic approach in creating more demanding WL that can potentially minimize toxicities in RT plans.
Plasticity-induced repression of Irf6 underlies acquired resistance to cancer immunotherapy
Authors: Kim Il-Kyu , Diamond Mark , Yuan Salina , Kemp Samantha , Li Qinglan , Lin Jeffrey , Li Jinyang , Norgard Robert , Thomas Stacy , Merolle Maria , Katsuda Takeshi , Tobias John , Politi Katerina , Vonderheide Robert , Stanger Ben
Published: June 2023

Acquired resistance to immune checkpoint immunotherapy remains a critical yet incompletely understood biological mechanism. Here, using a mouse model of pancreatic ductal adenocarcinoma (PDAC) to study tumor relapse following immunotherapy-induced responses, we found that tumors underwent an epithelial-to-mesenchymal transition (EMT) that resulted in reduced sensitivity to T cell-mediated killing. EMT-transcription factors (EMT-TFs) ZEB1 and SNAIL function as master genetic and epigenetic regulators of this tumor-intrinsic effect. Acquired resistance was not due to immunosuppression in the tumor immune microenvironment, disruptions in the antigen presentation machinery, or altered expression of immune checkpoints. Rather, EMT was associated with epigenetic and transcriptional silencing of interferon regulatory factor 6 (Irf6), which renders tumor cells less sensitive to the pro-apoptotic effects of TNF-α. These findings show how resistance to immunotherapy in PDAC can be acquired through plasticity programs that render tumor cells impervious to T cell killing.
Dissecting transcription of the 8q24-MYC locus in prostate cancer recognizes the equilibration between androgen receptor direct and indirect dual-functions
Authors: Guo Ju , Wei Zhao , Jia Tianwei , Wang Liyang , Nama Nuosu , Liang Jiaqian , Liao Xinghua , Liu Xiaming , Gao Yanfei , Liu Xiaoqiang , Wang Keshan , Fu Bin , Chen Shaoyong Shawn
Published: June 2023

Background：Androgen receptor (AR) activation and repression dual-functionality only becomes known recently and still remains intriguing in prostate cancer (PCa). MYC is a prominent oncogene functionally entangled with AR signaling in PCa. However, AR regulatory mechanisms on MYC gene transcription remains unclear.
Methods：Bioinformatics analysis of androgen-mediated RNA-Seq and MYC ChIP-Seq datasets are used for AR and MYC transcriptional networks. AR ChIP-qPCR analysis are programed to find AR binding sites (ABSs) which regulate MYC transcription. 3C-qPCR and 3C-ddPCR analyses affirmed androgen-dependent MYC-Pro-P10 interaction. CRISPR/Cas9-mediated double genomic knock-out (KO) strategy is used to show that P10-KO slightly lessened androgen-elicited MYC transrepression.
Results：Here we recognize AR bi-directional transcription mechanisms by exploiting the prominent 8q24-MYC locus conferring androgen hyper-sensitivity. At ~25Kb downstream of the MYC gene, we identified an undefined ABS, P10. By chromatin analyses, we validated androgen-dependent spatial interaction between P10 and MYC-Promoter (MYC-Pro) and temporal epigenetic repression of these MYC-proximal elements. We next designed a CRISPR/Cas9-mediated double genomic knock-out (KO) strategy to show that P10-KO slightly lessened androgen-elicited MYC transrepression in LNCaP-AR cells. In similar genomic editing assays, androgen-mediated MYC repression became slightly deepened upon KO of P11, an ABS in the PVT1 gene locus highly enriched in AR-binding motifs and peaks. We also investigated multiple ABSs in the established PCAT1 super-enhancer that distally interacts with MYC-Pro for transactivation, with each KO pool consistently shown to relieve androgen-elicited MYC repression. In the end, we systemically assessed androgen effects in the 8q24-MYC locus and along PCa genome to generalize H3K27ac and BRD4 re-distribution from pioneer factors (FoxA1 and HoxB13) to AR sites.
Conclusion：Together, we reconciled these observations by unifying AR dual-functions that are mechanistically coupled to and equilibrated by co-factor redistribution.
Evaluation of case-based combined with team-based learning guided blended learning on standardized residency training
Authors: Ling Xin , Zuyi Chen , Jin Yunxiu , Min Nie
Published: June 2023

Background
School and Hospital of Stomatology, Wuhan University has launched a special teaching mode in resident standardized training, called Case-based learning (CBL) combined with team-based learning (TBL) guided “blended learning”. It is adopted to fully stimulate students’ awareness of independent learning and develop personalized diagnosis and treatment plans through clinical department rotation, regular group learning and clinical lectures. Taking the specialty of endodontics as an example, this study introduces the specific content of this special teaching model, and evaluates the satisfaction of residents including postgraduate students and social residents, and its’ effect.
Methods
In the continuing education of standardized residency training, CBL combined with TBL guided online and offline “blended learning” method was used with professional postgraduate students and social residents as the main body, and a training model of“teacher as the guidance and team as the cooperation”was constructed. In addition to the rotation of clinical departments, the teaching methods such as group learning and clinical lecture were proposed. The original theoretical teaching and autonomous learning was supported, too. An anonymous questionnaire survey was conducted to analyze the the satisfaction of residents and teaching effects.
Results
The CBL combined with TBL guided“blended learning”mode was significantly better than the traditional theory teaching and autonomous learning, and gained a high satisfaction among the students. Except for the clinical lecture, clinical departments rotation and group learning gained a higher satisfaction compared with traditional theory teaching and autonomous learning, the differences were statistically significant (P < 0.05). Students generally though that clinical lectures and group learning were beneficial to improve their clinical thinking ability and enrich their knowledge system. 75.73% of the students thought that clinical lectures with the combination of clinical subject discussion and case report were more conducive to the formulation of personalized diagnosis and treatment plans.
Conclusions
In the process of standardized residency training, CBL combined with TBL guided “blended learning” mode is conducive to the cultivation of research doctors with clinical research thinking ability and make up personalized diagnosis and treatment plans for patients.