bluuebunny/crossref_metadata_2025 huggingface dataset:
Indian Navy’s Submarine Development Programme: A Critical Assessment
Authors: Ramkumar K. G. , Panneerselvam Prakash
Published: November 2023

In the twenty-first century, undersea warfare is changing. The role of submarines and ASW is also adapting to the new maritime environment in the Indo-Pacific region. The Submarine arm of the Indian Navy plays a crucial role in this region. Except for the four recently inducted Scorpene submarines, the other conventional submarines are more than two decades old. India’s ageing submarine fleet calls for greater focus on submarine acquisition. The 30-year (2000–2030) submarine building plan drawn up in 1998 envisaged the development of two parallel lines of six conventional submarines, to be constructed in India over twelve years. This is to be followed by 12 submarines of indigenous design based on the learning curve of the two lines to be constructed over the next twelve years. But, as of now, Project 75 has been planned for six submarines (with French design) in 2006, of which five are on active duty and the last one is undergoing sea trials. Project 75I has been sanctioned to build six submarines but with a new model involving two Indian firms, with the introduction of a strategic partner from the private sector to encourage their participation in the ‘Make in India’ policy. Despite India’s capability to design, develop, build and operate strategic submarines with very high indigenous content, India’s lack of capability to design conventional submarines raises the following questions, which this paper has tried to address: Is it related to inadequacies in capability or policy decision-making? Are there inconsistencies in defence procurement policy/procedure? Is there a need to evaluate the Strategic Partnership model before implementation? Is there a lack of access to technology?
Educational Technology to Promote Social Entrepreneurship Education in the COVID Pandemic Era
Authors: Hazarika Nibedita , Dagar Kriti
Published: November 2023

The objective of this study was to assess the literature, on the intersection of technology and social entrepreneurship. It involved conducting analyses by interviewing five entrepreneurs and analyzing the narratives of five governmental organizations that cater to educational needs in Delhi NCR.

Through these interviews the study delved into how technology and entrepreneurship impact the access to education for marginalized communities. To analyze both literature and real-life examples from entrepreneurs the ATLAS.ti coding program was employed. Codes and concepts were generated from the data in a manner for analyzing the literature. These codes and concepts were then used deductively to analyze the instances of entrepreneurs using an approach that helps us interpret data and gain new insights.

The study filled a gap in knowledge by examining how new technologies can be utilized to create business models that benefit populations. By highlighting the importance of technology among communities for social and economic progress it contributes to the understanding of social innovation and entrepreneurship. Additionally, it provided considerations for technology innovation within contexts.

The findings from this research highlighted challenges faced by both social entrepreneurs and organizations working with disadvantaged populations. One major obstacle identified was access to technology. Insufficient financial resources and ineffective resource utilization are also seen as hindrances. Lastly enhancing skills, among groups is emphasized as crucial for effectively promoting education.
Evaluating the impact of social housing policies: Measuring accessibility changes when individuals move to social housing projects
Authors: Lopes Flavia , Figueiredo Lucas , Gil Jorge , Trigueiro Edja
Published: November 2023

Addressing housing deficits and inequalities remains a key challenge for cities in promoting more sustainable urban development. In response to these challenges, governments around the world, particularly in the Global South, have made substantial investments in housing policies for middle- and low-income individuals. Nevertheless, while these initiatives increase housing provision, they often face criticism for not adequately considering the location of new residences. This oversight has far-reaching effects on the accessibility to essential facilities, which play a pivotal role in determining spatial advantages and disadvantages, and consequently, in the degree of inclusion of individuals in both the city and society. Addressing this critical role of accessibility, this paper introduces a methodology for assessing the potential impact of housing policies on the lives of their beneficiaries, by quantifying changes in cumulative accessibility levels between individuals' former house locations and the location of the housing projects into which they moved. Accessibility is calculated for three distinct transport modes: walking, cycling, and public transport, using unimodal and multimodal urban network models. A case study was conducted in Natal, northeastern Brazil, on the implementation of the Minha Casa, Minha Vida (My House, My Life, MCMV) housing policy, initiated in 2009 and still active today. The results of the study revealed a significant decrease in accessibility across all transportation modes when individuals moved to the new housing estates. The decline was particularly pronounced among individuals with lower incomes, potentially raising their regular expenses after relocation and, ultimately, leading to spatial isolation and social exclusion. These findings demonstrate the contribution of the methodology to capturing the impacts of housing policies on the everyday accessibility of their beneficiaries, while emphasizing the importance of re-evaluating these policies with a particular focus on fostering the social and urban inclusion of beneficiaries.
The Influence of Aging on the Structure and Properties of Composite Materials Based on Polyurethane and Silver Nanoparticles
Authors: Lysenkov Eduard A. , Striutskyi Oleksandr V.
Published: November 2023

The aging processes and their influence on structure, thermophysical and antimicrobial properties of polymer nanocomposites based on segmented polyurethane and silver nanoparticles were studied. It was established that an increase in the intensity of intermolecular interactions of polyurethane occurred regardless of the concentration of silver in the silver nanoparticles due to a change in the packing of macromolecules. It was shown that in the process of aging of composites, the effective size of crystallites of polymer matrix decreases and varies in the range of 1.35–1.50 nm. The most pronounced effect of aging is manifested on the melting temperatures of the crystalline phase of polyurethane and the degree of crystallinity. It was found that polyurethane–silver nanoparticle composites exhibit a very high inhibitory capacity against Staphylococcus aureus, Escherichia coli, and Candida albicans. It is shown that aging processes do not affect the antimicrobial characteristics of the studied materials, which indicates their stability. Due to their unique characteristics, synthesized nanocomposite films can be promising for use as antimicrobial coatings in various applications.
The Lighthouse Framework: Proposing a Movement-Based Constructivist Framework for Early Childhood Music Education and Pre-Service Education Programs
Authors: Ho Weatherly Katy Ieong Cheng , Weatherly Christopher Alan
Published: November 2023

This article aims to provide practical strategies and examples for pre-service early education programs and early education teachers to develop music- and movement-based curricula for teacher preparation programs and early childhood music classrooms. To address the inconsistencies in early childhood music programs, the authors developed the Lighthouse Framework, which utilizes constructivist ideology to help students learn through and adapt the teaching model while simultaneously learning music- and movement-based content. Through this proposed framework, pre-service teachers can gain authentic teaching experience, real-time feedback, and an adaptable framework for their future curriculum planning.
Creating an Inclusive Music Classroom
Authors: Liu Chiao-Wei
Published: November 2023

In this column, I shared my experiences of inviting students to bring in their “funds of knowledge” into the classroom. Acknowledging the diverse cultures in the classroom, I am interested in how students’ funds of knowledge can be celebrated, sustained, and potentially transformed into collective knowledge. Specifically, I am curious how different music traditions and styles interact and generate new conversations. Through this experience, I came to realize the importance of addressing the historical burden many minoritized carry and wonder, “can I be more than the race you see on me?” I share my own experiences to encourage fellow teachers to continue reflecting and attending to the students in front of us. Creating an inclusive classroom requires us to go beyond the present and create space for the changing, the emerging, and the unknown, through which our students may be more than what we know and build a better world.
Synthetic CRISPR/dCas9-KRAB system driven by specific PSA promoter suppresses malignant biological behavior of prostate cancer cells through negative feedback inhibition of PSA expression
Authors: Yang Yi , Mei Hongbing , Han Xiaohong , Zhang Xintao , Cheng Jianli , Zhang Zhongfu , Wang Han , Xu Haixia
Published: November 2023

PSA is a type of proto-oncogene that is specifically and highly expressed in embryonic and prostate cancer cells, but not expressed in normal prostate tissue cells. The specific expression of prostate-specific antigen (PSA) is found to be related with the conditional transcriptional regulation of its promoter. Clustered regularly interspaced short palindromic repeats (CRISPR)-dCas9-KRAB is a newly developed transcriptional regulatory system that inhibits gene expression by interupting the DNA transcription process. Induction of CRISPR-dCas9-KRAB expression through the PSA promoter may help feedback inhibition of cellular PSA gene expression via single guide RNA (sgRNA), thereby monitoring and suppressing the malignant state of tumor cells. In this study, we examined the transcriptional activity of the PSA promoter in different prostate cancer cells and normal prostate epithelial cells and determined that it is indeed a prostate cancer cell-specific promoter.Then we constructed the CRISPR-dCas9-KRAB system driven by the PSA promoter, which can inhibit PSA gene expression in the prostate cancer cells at the transcriptional level, and therefore supress the malignant growth and migration of prostate cancer cells and promote their apoptosis in vitro. This study provides a potentially effective anti-cancer strategy for gene therapy of prostate cancer.
A machine learning one-class logistic regression model to predict stemness for single cell transcriptomics and spatial omics
Authors: Dezem Felipe Segato , Marção Maycon , Ben-Cheikh Bassem , Nikulina Nadya , Omotoso Ayodele , Burnett Destiny , Coelho Priscila , Hurley Judith , Gomez Carmen , Phan-Everson Tien , Ong Giang , Martelotto Luciano , Lewis Zachary R. , George Sophia , Braubach Oliver , Malta Tathiane M. , Plummer Jasmine
Published: November 2023

Cell annotation is a crucial methodological component to interpreting single cell and spatial omics data. These approaches were developed for single cell analysis but are often biased, manually curated and yet unproven in spatial omics. Here we apply a stemness model for assessing oncogenic states to single cell and spatial omic cancer datasets. This one-class logistic regression machine learning algorithm is used to extract transcriptomic features from non-transformed stem cells to identify dedifferentiated cell states in tumors. We found this method identifies single cell states in metastatic tumor cell populations without the requirement of cell annotation. This machine learning model identified stem-like cell populations not identified in single cell or spatial transcriptomic analysis using existing methods. For the first time, we demonstrate the application of a ML tool across five emerging spatial transcriptomic and proteomic technologies to identify oncogenic stem-like cell types in the tumor microenvironment.
Association of gastrointestinal symptoms and skipping breakfast with anxiety and depressive symptoms in quarantined Chinese college students during the Shanghai 2022 lockdown: a cross sectional survey
Authors: Qiao Tingting , Gao Dingwei , Lu Gaixia , Yi Wanwan , Lv Zhongwei
Published: November 2023

Background

This study aimed to evaluate the prevalence of anxiety and depressive symptoms among quarantined college students at school in Shanghai 2022 lockdown during the COVID-19 pandemic and investigate the association of gastrointestinal discomfort related-factors and skipping breakfast with anxiety and depressive symptoms.

Methods

384 quarantined college students in Shanghai China were recruited in this cross-sectional study from April 5th to May 29th, 2022. Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) were used to assess anxiety and depressive symptoms, respectively.

Results

The prevalence of anxiety and depressive symptoms were 56.8% and 62.8%, respectively. Longer quarantine duration, higher education level, skipping breakfast, stomachache or abdominal pain, and nausea or dyspepsia were significantly associated with anxiety symptoms. Moreover, longer quarantine duration, being woman, skipping breakfast, stomachache or abdominal pain, and nausea or dyspepsia were markedly related to depressive symptoms. Notably, regularly physical exercising and taking positive attitude towards COVID-19 were negatively correlated with anxiety and depressive symptoms.

Conclusions

More attention should be paid to anxiety and depressive symptoms of quarantined college students and universities should provide timely psychological monitoring and intervention services to mitigate the impact of negative emotions on students. Effectively relieving gastrointestinal symptoms, insisting on eat breakfast, regularly exercising, and taking a positive attitude towards to COVID-19 might contribute to preventing the anxiety and depressive symptoms for those college students experiencing a long-term quarantine.
Prospective study of antidepressant treatment of psychiatric patients with depressive disorders: treatment adequacy and outcomes
Authors: von Knorring Johanna , Baryshnikov Ilya , Jylhä Pekka , Talaslahti Tiina , Heikkinen Martti , Isometsä Erkki
Published: November 2023

Background

Despite numerous national depression care guidelines (DCGs), suboptimal antidepressant treatment may occur. We examined DCG concordance and depression treatment outcomes in psychiatric settings.

Methods

We evaluated treatment received and outcomes of 128 psychiatric out- and inpatients participating in the PEGAD (Pharmacoepidemiology and Pharmacogenetics of Antidepressant Treatment for Depressive Disorders) study at baseline, two weeks, and eight weeks using interviews and questionnaires. Inclusion criteria were ICD-10 diagnosis of a depressive disorder, a Patient Health Questionnaire-9 symptom (PHQ-9) score ≥ 10, and a new antidepressant prescribed. The primary outcome of the study was within-individual change in PHQ-9 scores.

Results

At baseline, patients had predominately recurrent (83%) and in 19% treatment-resistant depression (TRD). The median preceding duration of the current episode was 6.5 months. At eight weeks, 85% of the patients (n = 107) used a DCG-concordant antidepressant dose. However, due to the scarcity of antidepressant combinations and augmentations, fewer TRD than non-TRD patients (25% vs. 84%, p < 0.005) received adequate antidepressant treatment. Additionally, one-third of the patients received inadequate follow-up. Overall, only 53% received treatment compatible with DCG recommendations for adequate pharmacotherapy and follow-up. The mean decline in PHQ-9 scores (-3.8 ± SD 5.7) was significant (p < 0.0005). Nearly 40% of the patients reached a subthreshold level of depression (PHQ-9 < 10), predicted by a lower baseline PHQ-9 score, recurrent depression, and female sex. However, 45% experienced no significant clinical improvement (PHQ-9 score reduction < 20%).

Conclusions

Our findings suggest that inadequate treatment continues to occur in psychiatric care settings, particularly for TRD patients.
Muscle dynamics analysis by clustered categories during jogging in patients with anterior cruciate ligament deficiency
Authors: Li Haoran , Huang Hongshi , Zhang Si , Ren Shuang , Rong Qiguo
Published: November 2023

Background

Patients with anterior cruciate ligament (ACL) deficiency (ACLD) tend to have altered lower extremity dynamics. Little is known about the changes in dynamic function and activation during jogging in patients with ACLD.

Methods

Twenty patients with an injured ACL before ACL reconstruction (ACLD group) and nine healthy male volunteers (control group) were recruited. Each volunteer repeated the jogging experiment five times. Based on the experimental data measured, a musculoskeletal multibody dynamics model was employed to simulate the tibiofemoral joint dynamics during jogging. Eighteen muscles were used for analysis. The obtained dynamics data were used for clustering and curve difference analysis.

Results

The 18 muscles studied were divided into 3 categories. All the quadriceps, the soleus, the gastrocnemius, and the popliteus were classified as label 1. All the hamstrings were classified as label 2, and the sartorius muscles were classified as label 3. Among them, the classification of the short head of the biceps femoris was significantly different between the two groups (P < 0.001). The force curves of all 18 muscles and the between-group differences were studied according to clustered categories. Most muscle force in label 1 was approaching zero in the terminal stance phase, which was significantly lower than that in the control group (P < 0.05). The muscle force in label 2 had areas with significant differences in the stance phase. Muscle force in label 3 was significantly lower than that in the control group in the pre-swing phase.

Conclusions

This study showed that there are various changes of muscle function and activation in patients with ACLD. Through clustering and curve analysis, the joint reactions and changes of different muscle forces in the gait cycle between the ACLD and control groups could be further clarified.
A comparative study of flexible ureteroscopic lithotripsy for upper urinary tract stones in patients with prior urosepsis following emergency drainage via retrograde ureteral stent or percutaneous nephrostomy
Authors: Liao Sucai , Xu Xiang , Yuan Yuan , Tang Keiyui , Wei Genggeng , Lu Zhengquan , Xiong Lin
Published: November 2023

Background

Patients with urosepsis associated with upper urinary tract stones require further stone management after emergency drainage.

Objective

To evaluate the safety and efficacy of elective flexible ureteroscopic lithotripsy (F-URSL) for upper urinary tract stones in patients with prior urosepsis who have undergone emergency drainage using retrograde ureteral stent(RUS) or percutaneous nephrostomy (PCN).

Method

Between January 2017 and December 2021, clinical data were collected for 102 patients who underwent elective F-URSL following emergency drainage for urosepsis caused by upper ureteral or renal stones. The patients were categorized into two groups based on the drainage method used: the RUS group and the PCN group. The collected data included patient demographics, stone parameters, infection recovery after emergency drainage, and clinical outcomes post F-URSL. Subsequently, the data underwent statistical analysis.

Results

A total of 102 patients were included in the statistical analysis, with 58 (56.86%) in the RUS group and 44 (43.14%) in the PCN group. Among the patients, 84 (82.35%) were female and 18 (17.65%) were male, with an average age of 59.36 years. Positive urine cultures were observed in 71 (69.61%) patients. Successful drainage was achieved in all patients in both groups, and there were no significant differences in the time required for normalization of white blood cell count (WBC) and body temperature following drainage. Additionally, all patients underwent F-URSL successfully, and no statistically significant differences were observed between the two groups in terms of operative time, stone-free rates, postoperative fever, and postoperative hospital stay.

Conclusion

Both RUS and PCN have been established as effective approaches for managing urosepsis caused by upper urinary tract stones. Furthermore, the impact of these two drainage methods on the subsequent management of stones through elective F-URSL has shown consistent outcomes.
Comparison effects of Ferula gummosa essential oil and Beta-pinene Alginate nanoparticles on human melanoma and breast cancer cells proliferation and apoptotic index in short term normobaric hyperoxic model
Authors: Osanloo Mahmoud , Pishamad Somayyeh , ghanbariasad Ali , Zarenezhad Elham , Alipanah Media , Alipanah Hiva
Published: November 2023

Background

Breast cancer is the most common cancer among women, and melanoma is the most dreadful type of skin cancer. Due to the side effects of chemotherapy drugs, the development of new herbal nano-medicines has been considered.

Methods

This study first investigated the chemical composition of Ferula gummosa essential oil using GC-MS analysis; β-pinene, with 61.57%, was the major compound. Next, alginate nanoparticles containing β-pinene and the essential oil with particle sizes of 174 ± 7 and 137 ± 6 nm were prepared. Meanwhile, their zeta potentials were 12.4 ± 0.7 and 28.1 ± 1 mV. Besides, the successful loading of β-pinene and the essential oil in nanoparticles was confirmed using ATR-FTIR analysis. After that, their effects on viability and apoptotic index of human melanoma and breast cancer cells were investigated in normoxia and normobaric hyperoxia (NBO) conditions.

Results

The best efficacy on A-375 and MDA-MB-231 cells was achieved by alginate nanoparticles containing the EO at hyperoxic and normoxia conditions; IC50 76 and 104 µg/mL. Besides, it affected apoptosis-involved genes; as Bax/Bcl-2 ratio was higher than 1, conditions for induction of apoptosis were obtained. Higher sensitivity was observed in the A-375 cell line treated with Alg-EO in the NBO model.

Conclusions

Alginate nanoparticles containing F. gummosa EO could be considered for further investigation in anticancer studies. Also, it may be expected that NBO can be a new strategy for delaying cancer progression and improving nanotherapy efficacy.
A comparison between a maximum care university hospital and an outpatient clinic – potential for optimization in arthroscopic workflows?
Authors: Schenk Martin , Neumann Juliane , Adler Nadine , Trommer Tilo , Theopold Jan , Neumuth Thomas , Hepp Pierre
Published: November 2023

Background

Due to the growing economic pressure, there is an increasing interest in the optimization of operational processes within surgical operating rooms (ORs). Surgical departments are frequently dealing with limited resources, complex processes with unexpected events as well as constantly changing conditions. In order to use available resources efficiently, existing workflows and processes have to be analyzed and optimized continuously. Structural and procedural changes without prior data-driven analyses may impair the performance of the OR team and the overall efficiency of the department. The aim of this study is to develop an adaptable software toolset for surgical workflow analysis and perioperative process optimization in arthroscopic surgery.

Methods

In this study, the perioperative processes of arthroscopic interventions have been recorded and analyzed subsequently. A total of 53 arthroscopic operations were recorded at a maximum care university hospital (UH) and 66 arthroscopic operations were acquired at a special outpatient clinic (OC). The recording includes regular perioperative processes (i.a. patient positioning, skin incision, application of wound dressing) and disruptive influences on these processes (e.g. telephone calls, missing or defective instruments, etc.). For this purpose, a software tool was developed (‘s.w.an Suite Arthroscopic toolset’). Based on the data obtained, the processes of the maximum care provider and the special outpatient clinic have been analyzed in terms of performance measures (e.g. Closure-To-Incision-Time), efficiency (e.g. activity duration, OR resource utilization) as well as intra-process disturbances and then compared to one another.

Results

Despite many similar processes, the results revealed considerable differences in performance indices. The OC required significantly less time than UH for surgical preoperative (UH: 30:47 min, OC: 26:01 min) and postoperative phase (UH: 15:04 min, OC: 9:56 min) as well as changeover time (UH: 32:33 min, OC: 6:02 min). In addition, these phases result in the Closure-to-Incision-Time, which lasted longer at the UH (UH: 80:01 min, OC: 41:12 min).

Conclusion

The perioperative process organization, team collaboration, and the avoidance of disruptive factors had a considerable influence on the progress of the surgeries. Furthermore, differences in terms of staffing and spatial capacities could be identified. Based on the acquired process data (such as the duration for different surgical steps or the number of interfering events) and the comparison of different arthroscopic departments, approaches for perioperative process optimization to decrease the time of work steps and reduce disruptive influences were identified.
Clarity and adaptability of instructions preventing the spread of the COVID-19 virus and its association with individual and organisational factors regarding the psychosocial work environment: a cross-sectional study
Authors: Hammar Lena Marmstål , Alam Moudud , Eklund Caroline , Boström Anne-Marie , Lövenmark Annica
Published: November 2023

Background

In Sweden, older people in residential care had the highest mortality rates, followed by those who received home care, during the coronavirus disease 2019 (COVID-19) pandemic. Staff working in the care of older people assumed responsibility for preventing the spread of the virus despite lacking the prerequisites and training. This study aimed to investigate the psychosocial work environment during the COVID-19 pandemic among staff in the care of older people and examine the factors associated with staff’s perceptions of the clarity of instructions and the ability to follow them.

Methods

A cross-sectional study design was employed using a web survey. The staff’s perceptions of their psychosocial environment were analysed using descriptive statistics. The association between organisational and individual factors, as well as the degree of clarity of the instructions and the staff’s ability to follow them, were assessed using multivariate (ordinal) regression analysis.

Results

The main findings show that perceptions of the clarity and adaptability of the instructions were primarily correlated with organisational factors, as higher responses (positive) for the subscales focusing on role clarity, support and encouragement in leadership at work were associated with the belief that the instructions were clear. Similarly, those indicating high job demands and high individual learning demands were less likely to report that the instructions were clear. Regarding adaptability, high scores for demands on learning and psychological demands were correlated with lower adaptability, while high scores for role clarity, encouraging leadership and social support, were associated with higher adaptability.

Conclusions

High job demands and individual learning demands were demonstrated to decrease the staff’s understanding and adoption of instructions. These findings are significant on an organisational level since the work environment must be prepared for potential future pandemics to promote quality improvement and generally increase patient safety and staff health.
Calf morbidity, mortality, and management practices in dairy farms in Jimma City, Southwestern Ethiopia
Authors: Ahmedin Umer Mifta , Assen Alula Alemayehu
Published: November 2023

Background

This research aims to determine the incidence of calf morbidity, mortality and its potential predisposing factors in the first six months of life. Morbidity and mortality of dairy calves are persistent problems for dairy farmers worldwide. For effective control and prevention programs on calf health, it is imperative to estimate the extent of calf morbidity and mortality, and associated risk factors. Although few studies have investigated the epidemiology of calf morbidity and mortality in Ethiopia, comprehensive information is scarce in this area.

Methods

Data were collected through a cross-sectional survey and longitudinal follow-up on purposively selected dairy farms. A longitudinal study was conducted on 235 calves from birth to 6 months of age. Survival analysis methods using the Kaplan–Meier (K-M) method, and mixed effect Cox proportional hazard regression were employed to compute the life-to-event data on morbidity and mortality.

Results

From the 235 calves studied, 53 morbidity and 15 mortality events were recorded. This gives an overall morbidity and mortality incidence rate of 55 per 100-calf 6-months at risk (risk rate of 42.07%) and 14 per 100-calf 6-months at risk (risk rate of 12.97%), respectively. Diarrhea (13.84%) followed by pneumonia (8.97%) were the most common diseases that occurred in calves, respectively. Similarly, diarrhea (33.3%) and pneumonia (26.7%) were the leading causes of death. Dam parity (p < 0.001) and pen cleaning (p < 0.001) were significant predictors of calf morbidity. Dam parity (p = 0.007), calving status (p = 0.005), pen cleaning (p = 0.04), and floor type (p = 0.001) of houses were significantly associated with mortality. The hazard of diarrhea was significantly associated with sex (p = 0.003), first colostrum feeding time (p = 0.028), pen cleaning (p = 0.010), and breeding method (p = 0.013).

Conclusion

The rates of morbidity and mortality reported in the study were higher than the economically acceptable, also affecting the welfare of the animals. The risk factors found need due attention in the management practices of dairy calves in Ethiopia.
Sulfate limitation increases specific plasmid DNA yield and productivity in E. coli fed-batch processes
Authors: Gotsmy Mathias , Strobl Florian , Weiß Florian , Gruber Petra , Kraus Barbara , Mairhofer Juergen , Zanghellini Jürgen
Published: November 2023

Plasmid DNA (pDNA) is a key biotechnological product whose importance became apparent in the last years due to its role as a raw material in the messenger ribonucleic acid (mRNA) vaccine manufacturing process. In pharmaceutical production processes, cells need to grow in the defined medium in order to guarantee the highest standards of quality and repeatability. However, often these requirements result in low product titer, productivity, and yield. In this study, we used constraint-based metabolic modeling to optimize the average volumetric productivity of pDNA production in a fed-batch process. We identified a set of 13 nutrients in the growth medium that are essential for cell growth but not for pDNA replication. When these nutrients are depleted in the medium, cell growth is stalled and pDNA production is increased, raising the specific and volumetric yield and productivity. To exploit this effect we designed a three-stage process (1. batch, 2. fed-batch with cell growth, 3. fed-batch without cell growth). The transition between stage 2 and 3 is induced by sulfate starvation. Its onset can be easily controlled via the initial concentration of sulfate in the medium. We validated the decoupling behavior of sulfate and assessed pDNA quality attributes (supercoiled pDNA content) in E. coli with lab-scale bioreactor cultivations. The results showed an increase in supercoiled pDNA to biomass yield by 33% and an increase of supercoiled pDNA volumetric productivity by 13 % upon limitation of sulfate. In conclusion, even for routinely manufactured biotechnological products such as pDNA, simple changes in the growth medium can significantly improve the yield and quality.

Graphical Abstract
Comparison of deep learning-based image segmentation methods for intravascular ultrasound on retrospective and large image cohort study
Authors: Dong Liang , Lu Wei , Lu Xuzhou , Leng Xiaochang , Xiang Jianping , Li Changling
Published: November 2023

Objectives

The aim of this study was to investigate the generalization performance of deep learning segmentation models on a large cohort intravascular ultrasound (IVUS) image dataset over the lumen and external elastic membrane (EEM), and to assess the consistency and accuracy of automated IVUS quantitative measurement parameters.

Methods

A total of 11,070 IVUS images from 113 patients and pullbacks were collected and annotated by cardiologists to train and test deep learning segmentation models. A comparison of five state of the art medical image segmentation models was performed by evaluating the segmentation of the lumen and EEM. Dice similarity coefficient (DSC), intersection over union (IoU) and Hausdorff distance (HD) were calculated for the overall and for subsets of different IVUS image categories. Further, the agreement between the IVUS quantitative measurement parameters calculated by automatic segmentation and those calculated by manual segmentation was evaluated. Finally, the segmentation performance of our model was also compared with previous studies.

Results

CENet achieved the best performance in DSC (0.958 for lumen, 0.921 for EEM) and IoU (0.975 for lumen, 0.951 for EEM) among all models, while Res-UNet was the best performer in HD (0.219 for lumen, 0.178 for EEM). The mean intraclass correlation coefficient (ICC) and Bland–Altman plot demonstrated the extremely strong agreement (0.855, 95% CI 0.822–0.887) between model's automatic prediction and manual measurements.

Conclusions

Deep learning models based on large cohort image datasets were capable of achieving state of the art (SOTA) results in lumen and EEM segmentation. It can be used for IVUS clinical evaluation and achieve excellent agreement with clinicians on quantitative parameter measurements.
Identification and characterization of ARID1A-interacting proteins in renal tubular cells and their molecular regulation of angiogenesis
Authors: Yoodee Sunisa , Peerapen Paleerath , Plumworasawat Sirikanya , Malaitad Thanyalak , Thongboonkerd Visith
Published: November 2023

Background

Defects and deficiency of AT-rich interactive domain-containing protein 1A (ARID1A) encoded by a tumor suppressor gene ARID1A have recently been suggested to get involved in angiogenesis, a crucial process in carcinogenesis. However, molecular mechanisms of ARID1A deficiency to induce angiogenesis in kidney cancer remain underinvestigated.

Methods

We performed large-scale identification of ARID1A protein interactors in renal tubular epithelial cells (RTECs) using immunoprecipitation (IP) followed by nanoLC-ESI-LTQ-Orbitrap tandem mass spectrometry (MS/MS). Their roles in angiogenesis were investigated using various assays.

Results

A total of 74 ARID1A-interacting proteins were identified. Protein–protein interactions analysis revealed that these identified proteins interacted directly or indirectly with ARID1A. Among them, the direct interaction between ARID1A and β-actin was validated by IP and reciprocal IP followed by Western blotting. Small interfering RNA (siRNA) was used for single and double knockdowns of ARID1A and ACTB. Semi-quantitative RT-PCR demonstrated that deficiency of ARID1A, but not ACTB, significantly affected expression of angiogenesis-related genes in RTECs (VEGF and FGF2 were increased, whereas PDGF and EGF were decreased). However, the knockdowns did not affect TGFB1 and FGF1 levels. The quantitative mRNA expression data of VEGF and TGFB1 were consistent with the secreted levels of their protein products as measured by ELISA. Only secreted products derived from ARID1A-deficient RTECs significantly increased endothelial cells (ECs) migration and tube formation. Some of the other carcinogenic features could also be confirmed in the ARID1A-deficient RTECs, including increased cell migration and chemoresistance. Double knockdowns of both ARID1A and ACTB did not enhance the effects of single ARID1A knockdown in all assays.

Conclusions

We report herein a large dataset of the ARID1A-interacting proteins in RTECs using an IP-MS/MS approach and confirm the direct interaction between ARID1A and β-actin. However, the role of ARID1A deficiency in angiogenesis is independent of β-actin.
Elucidating the clonal relationship of esophageal second primary tumors in patients with laryngeal squamous cell carcinoma
Authors: Wan Meixuan , Yang Xinxin , He Lin , Meng Hongxue
Published: November 2023

Laryngeal cancer ranks as the second most prevalent upper airway malignancy, following Lung cancer. Although some progress has been made in managing laryngeal cancer, the 5-year survival rate is disappointing. The gradual increase in the incidence of second primary tumors (SPTs) plays a crucial role in determining survival outcomes during long-term follow-up, and the esophagus was the most common site with a worse prognosis. In clinical practice, the treatment of esophageal second primary tumors (ESPT) in patients with laryngeal squamous cell carcinoma (LSCC) has always been challenging. For patients with synchronous tumors, several treatment modalities, such as radiotherapy, chemotherapy and potentially curative surgery are necessary but are typically poorly tolerated. Secondary cancer therapy options for metachronous patients are always constrained by index cancer treatment indications. Therefore, understanding the clonal origin of the second primary tumor may be an important issue in the treatment of patients. LSCC cells demonstrate genetic instability because of two distinct aetiologies (human papillomavirus (HPV)-negative and HPV-positive) disease. Various etiologies exhibit distinct oncogenic mechanisms, which subsequently impact the tissue microenvironment. The condition of the tissue microenvironment plays a crucial role in determining the destiny and clonal makeup of mutant cells during the initial stages of tumorigenesis. This review focuses on the genetic advances of LSCC, the current research status of SPT, and the influence of key carcinogenesis of HPV-positive and HPV-negative LSCC on clonal evolution of ESPT cells. The objective is to gain a comprehensive understanding of the molecular basis underlying the clonal origins of SPT, thereby offering novel perspectives for future investigations in this field.
The JUMPFOOD study: additional effect of hydrolyzed collagen and vitamin C to exercise treatment for patellar tendinopathy (jumper’s knee) in athletes—study protocol for a double-blind randomized controlled trial
Authors: van Dam L. , Terink R. , Mensink M. , de Vos R. J. , Zwerver J.
Published: November 2023

Background

Patellar tendinopathy (PT) is a common problem in jumping athletes. Management can be challenging and treatment outcome is not always successful. In combination with tendon loading exercises, hydrolyzed collagen/vitamin C supplementation appears to have a promising effect on the recovery of tendinopathy. The aim of this study is to evaluate whether the use of oral supplementation of hydrolyzed collagen and vitamin C in combination with progressive tendon loading exercises (PTLE) is superior to PTLE and placebo on VISA-P score (which rates pain, function, sports participation) after 24 weeks for athletes with PT.

Methods

The JUMPFOOD study is a double-blinded, two-armed randomized controlled trial, in which the effectiveness of oral supplementation of hydrolyzed collagen/vitamin C combined with PTLE compared to PTLE with placebo on pain and recovery of function in athletes with PT will be investigated. Seventy-six athletes aged 16–40 years, with symptoms of PT for at least 12 weeks, who play sports at least once a week will be included. All participants will receive education, advice with regard to load management and a PTLE program according to the Dutch guidelines for anterior knee pain. In addition, the intervention group will receive daily 10 g hydrolyzed collagen and 40 mg vitamin C supplementation for 24 weeks whereas the control group receives 10 g maltodextrin placebo supplementation. Measurements will take place at baseline and at 12 and 24 weeks’ follow-up. Primary outcome is the VISA-P score, which evaluates pain, function, and sports participation. For secondary outcome measures, data with regard to pain during functional tests, flexibility measurements, blood withdrawals, imaging characteristics of the tendon, and health questionnaires will be collected. During the follow-up period, participants will register sports participation, amount of training and tendon load, pain during sports, co-medication, and side-effects in a digital weekly diary.

Discussion

The JUMPFOOD study is the first large RCT to study the effectiveness of hydrolyzed collagen/vitamin C supplementation in combination with the PTLE program in athletes with patellar tendinopathy. If supplementation of collagen/vitamin C appears to be effective, this treatment can be implemented in daily sports medicine practice to improve the treatment outcome of patients with PT.

Trial registration

ClinicalTrials.gov NCT05407194. Registered on 7 June 2022.
Molecular analyses of zebrafish V0v spinal interneurons and identification of transcriptional regulators downstream of Evx1 and Evx2 in these cells
Authors: England Samantha J. , Rusnock Amber K. , Mujcic Amra , Kowalchuk Angelica , de Jager Sarah , Hilinski William C. , Juárez-Morales José L. , Smith Matthew E. , Grieb Ginny , Banerjee Santanu , Lewis Katharine E.
Published: November 2023

Background

V0v spinal interneurons are highly conserved, glutamatergic, commissural neurons that function in locomotor circuits. We have previously shown that Evx1 and Evx2 are required to specify the neurotransmitter phenotype of these cells. However, we still know very little about the gene regulatory networks that act downstream of these transcription factors in V0v cells.

Methods

To identify candidate members of V0v gene regulatory networks, we FAC-sorted wild-type and evx1;evx2 double mutant zebrafish V0v spinal interneurons and expression-profiled them using microarrays and single cell RNA-seq. We also used in situ hybridization to compare expression of a subset of candidate genes in evx1;evx2 double mutants and wild-type siblings.

Results

Our data reveal two molecularly distinct subtypes of zebrafish V0v spinal interneurons at 48 h and suggest that, by this stage of development, evx1;evx2 double mutant cells transfate into either inhibitory spinal interneurons, or motoneurons. Our results also identify 25 transcriptional regulator genes that require Evx1/2 for their expression in V0v interneurons, plus a further 11 transcriptional regulator genes that are repressed in V0v interneurons by Evx1/2. Two of the latter genes are hmx2 and hmx3a. Intriguingly, we show that Hmx2/3a, repress dI2 interneuron expression of skor1a and nefma, two genes that require Evx1/2 for their expression in V0v interneurons. This suggests that Evx1/2 might regulate skor1a and nefma expression in V0v interneurons by repressing Hmx2/3a expression.

Conclusions

This study identifies two molecularly distinct subsets of zebrafish V0v spinal interneurons, as well as multiple transcriptional regulators that are strong candidates for acting downstream of Evx1/2 to specify the essential functional characteristics of these cells. Our data further suggest that in the absence of both Evx1 and Evx2, V0v spinal interneurons initially change their neurotransmitter phenotypes from excitatory to inhibitory and then, later, start to express markers of distinct types of inhibitory spinal interneurons, or motoneurons. Taken together, our findings significantly increase our knowledge of V0v and spinal development and move us closer towards the essential goal of identifying the complete gene regulatory networks that specify this crucial cell type.
Integrated microbiology and metabolomic analysis reveal the improvement of rice straw silage quality by inoculation of Lactobacillus brevis
Authors: Sun Yu , Sun Qinglong , Tang Yunmeng , Li Qingyang , Tian Chunjie , Sun Haixia
Published: November 2023

Background

Ensiling technology holds promise for preserving and providing high-quality forage. However, the preservation of rice straw poses challenges due to its high lignocellulosic content and low water-soluble carbohydrate levels. Developing highly effective lactic acid bacteria (LAB) for rice straw silage remains a priority.

Results

This study evaluated the impact of three LAB strains, Lactobacillus brevis R33 (Lac33), L. buchneri R17 (Lac17), and Leuconostoc pseudomesenteroides (Leu), on the fermentation quality of rice straw silage. Rice straw silage inoculated with Lac33 alone or in combination with other strains exhibited significantly lower neutral detergent fiber (NDF) (66.5% vs. 72.3%) and acid detergent fiber (ADF) (42.1% vs. 47%) contents, along with higher lactic acid (19.4 g/kg vs. not detected) and propionic acid (2.09 g/kg vs. 1.54 g/kg) contents compared to control silage. Bacterial community analysis revealed Lactobacillus dominance (> 80%) and suppression of unwanted Enterobacter and Clostridium. Metabolomic analysis highlighted increased carbohydrates and essential amino acids, indicating improved nutrient values in Lac33-inoculated rice straw silage and a potential explanation for Lac33 dominance.

Conclusions

This research identified a highly efficient LAB candidate for rice straw silage, advancing our comprehension of fermentation from integrated microbiology and metabolomic perspectives.
Energetically exploiting lignocellulose-rich residues in anaerobic digestion technologies: from bioreactors to proteogenomics
Authors: Poulsen Jan Struckmann , Macêdo Williane Vieira , Bonde Torben , Nielsen Jeppe Lund
Published: November 2023

The biogas produced through anaerobic digestion (AD) of renewable feedstocks is one of the promising alternatives to replace fossil-derived energy. Even though lignocellulosic biomass is the most abundant biomass on earth, only a small fraction is being used towards resources recovery, leaving a great potential unexploited. In this study, the combination of state-of-art genomic techniques and engineered systems were used to further advance the knowledge on biogas production from lignocellulosic-rich residues and the microbiome involved in the anaerobic digestion hereof. A long-term adapted anaerobic microbiome capable of degrading wheat straw as the sole substrate was investigated using protein stable isotope probing (protein-SIP). The results indicated that a diverse microbial community, primarily composed of Firmicutes and Methanogens, played crucial roles in cellulose degradation and methane production. Notably, Defluviitoga tunisiensis, Syntrophothermus lipocalidus, and Pelobacter carbinolicus were identified as direct metabolizers of cellulose, while Dehalobacterium assimilated labelled carbon through cross-feeding. This study provides direct evidence of primary cellulose degraders and sheds light on their genomic composition. By harnessing the potential of lignocellulosic biomass and understanding the microbial communities involved, we can promote sustainable biogas production, contributing to energy security and environmental preservation.