bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokinetic engineering enhances the secretory production of recombinant human lysozyme in Komagataella phaffii
Authors: Zhong Yong-Jun , Luo Yang-Yang , Xia Haiyang , Zhao Qing-Wei , Mao Xu-Ming 
Published: June 2024

Abstract
Background
Human lysozyme (hLYZ) is a natural antibacterial protein with broad applications in food and pharmaceutical industries. Recombinant production of hLYZ in Komagataella phaffii (K. phaffii) has attracted considerable attention, but there are very limited strategies for its hyper-production in yeast.

Results
Here through Atmospheric and Room Temperature Plasma (ARTP)-based mutagenesis and transcriptomic analysis, the expression of two genes MYO1 and IQG1 encoding the cytokinesis core proteins was identified downregulated along with higher hLYZ production. Deletion of either gene caused severe cytokinesis defects, but significantly enhanced hLYZ production. The highest hLYZ yield of 1,052,444 ± 23,667 U/mL bioactivity and 4.12 ± 0.11 g/L total protein concentration were obtained after high-density fed-batch fermentation in the Δmyo1 mutant, representing the best production of hLYZ in yeast. Furthermore, O-linked mannose glycans were characterized on this recombinant hLYZ.

Conclusions
Our work suggests that cytokinesis-based morphology engineering is an effective way to enhance the production of hLYZ in K. phaffii.
Unprovoked venous thromboembolism recurrence and arterial embolism revealing lung cancer: a case report
Authors: Glodeanu Maria-Cristina , Mutruc Victoria , Apetrei Camelia-Maria , Ursaru Manuela , Sorodoc Laurentiu , Lionte Catalina 
Published: June 2024

AbstractThe link between venous thromboembolism (VTE) and cancer is well known. VTE could be the initial sign of an occult malignancy. There are more diagnoses of cancer after an unprovoked VTE compared to a provoked VTE, with a reported prevalence between 4.5% and 5.6% over 12 months, within the first 6 months of VTE diagnosis. There are no recommended guidelines and scores yet adopted in clinical practice, but many studies support occult cancer screening in unprovoked VTE patients. We report the case of a patient with a history of unprovoked pulmonary embolism (PE) diagnosed with bronchopulmonary neoplasm in an advanced stage one year after the thromboembolic event. When the cancer was first diagnosed, the patient’s condition was already serious, being too late for the adoption of measures meant to decrease the risk of mortality and increase the duration of survival. We wanted to emphasize the importance of occult cancer screening in patients with unprovoked VTE and the fact that early cancer diagnosis reduces the risk of cancer progression, decreasing mortality and morbidity related to it.
Activation of kappa opioid receptor suppresses post-traumatic osteoarthritis via sequestering STAT3 on the plasma membrane
Authors: Liu Haixia , Huang Renhuan , Zhuo Ziang , Zhang Xinru , Wu Ling , Guo Zhen , Wen Fuping , An Liwei , Yuan Hang , Zhang Yiming , Xu Yuanzhi 
Published: June 2024

Abstract
Objective
Kappa opioid receptor (KOR) signaling is involved in joint development and inflammation in Osteoarthritis (OA), while the biochemical mechanism remains unclarified. This study aims to investigate downstream molecular events of KOR activation, to provide novel perspectives in OA pathology.

Methods
U50,488H, a selective KOR agonist, was intra-articularly injected in mice upon destabilization of the medial meniscus (DMM) as OA models, with PBS injection as control. The behavioral and histological evaluation was assessed by hot plate test and red solid green staining, respectively. Alterations in mRNA and protein expression were assessed by RNA-seq, RT-qPCR, immunohistochemistry and western blotting (WB) in chondrocytes treated with TNF-α or TNF-α + U50,488H. Proteins interacted with KOR were explored using proximity labeling followed by mass spectrometry and then testified by co-immunoprecipitation (Co-IP) assay and immunofluorescence (IF).

Results
OA-induced pain was reduced and cartilage degeneration was alleviated upon KOR activation in DMM mice. In chondrocytes, activation of KOR reversed the upregulation of MMPs, IL-6, IL-1β and phosphorylated(p-) STAT3, stimulated by TNF-α, while the expression of NF-κB, MAPKs and AKT signaling weren't reversed. RNA-seq and IF results presented that KOR activation evidently reduced STAT3 nuclear translocation in chondrocytes upon TNF-α stimuli. The reduction may be resulted from the binding of KOR and STAT3 in the plasma membrane, revealed by proximity labeling and Co-IP results.

Conclusions
KOR activation protects cartilage from OA, and this protective effect is mainly exerted via sequestering STAT3 on the plasma membrane, resulting in inactivation of STAT3-dependent immune responses which otherwise contributes to OA.
Automatic gait events detection with inertial measurement units: healthy subjects and moderate to severe impaired patients
Authors: Voisard Cyril , de l’Escalopier Nicolas , Ricard Damien , Oudre Laurent 
Published: June 2024

Abstract
Background
Recently, the use of inertial measurement units (IMUs) in quantitative gait analysis has been widely developed in clinical practice. Numerous methods have been developed for the automatic detection of gait events (GEs). While many of them have achieved high levels of efficiency in healthy subjects, detecting GEs in highly degraded gait from moderate to severely impaired patients remains a challenge. In this paper, we aim to present a method for improving GE detection from IMU recordings in such cases.

Methods
We recorded 10-meter gait IMU signals from 13 healthy subjects, 29 patients with multiple sclerosis, and 21 patients with post-stroke equino varus foot. An instrumented mat was used as the gold standard. Our method detects GEs from filtered acceleration free from gravity and gyration signals. Firstly, we use autocorrelation and pattern detection techniques to identify a reference stride pattern. Next, we apply multiparametric Dynamic Time Warping to annotate this pattern from a model stride, in order to detect all GEs in the signal.

Results
We analyzed 16,819 GEs recorded from healthy subjects and achieved an F1-score of 100%, with a median absolute error of 8 ms (IQR [3–13] ms). In multiple sclerosis and equino varus foot cohorts, we analyzed 6067 and 8951 GEs, respectively, with F1-scores of 99.4% and 96.3%, and median absolute errors of 18 ms (IQR [8–39] ms) and 26 ms (IQR [12–50] ms).

Conclusions
Our results are consistent with the state of the art for healthy subjects and demonstrate a good accuracy in GEs detection for pathological patients. Therefore, our proposed method provides an efficient way to detect GEs from IMU signals, even in degraded gaits. However, it should be evaluated in each cohort before being used to ensure its reliability.
CRISPR/Cas9-mediated knock out of ITGB6 in human OSCC cells reduced migration and proliferation ability
Authors: Geyer Maximilian , Geyer Fabian , Reuning Ute , Klapproth Sarah , Wolff Klaus-Dietrich , Nieberler Markus 
Published: June 2024

AbstractBackgroundThe treatment of oral squamous cell carcinoma (OSCC) remains challenging and survival rates have not been improved significantly over the past decades. Integrins have been recognized driving the cancer progression and high expression levels cause poor outcomes in patients afflicted with OSCC. Integrin αvβ6 and its subunit integrin beta 6 (ITGB6) were discovered to enhance the invasiveness by providing beneficial effects on downstream pathways promoting the cancer progression. The objective of this study was to establish a CRISPR/Cas9-mediated knock out of ITGB6 in the human OSCC cell line HN and investigate the effects on the migration and proliferation ability.MethodsITGB6 knock out was performed using the CRISPR/Cas9-system, RNPs, and lipofection. Monoclonal cell clones were achieved by limiting dilution and knock out verification was carried out by sanger sequencing and FACS on protein level. The effects of the knock out on the proliferation and migration ability were evaluated by using MTT and scratch assays. In addition, in silico TCGA analysis was utilized regarding the effects of ITGB6 on overall survival and perineural invasion.ResultsIn silico analysis revealed a significant impact of ITGB6 mRNA expression levels on the overall survival of patients afflicted with OSCC. Additionally, a significantly higher rate of perineural invasion was discovered. CRISPR/Cas9-mediated knock out of ITGB6 was performed in the OSCC cell line HN, resulting in the generation of a monoclonal knock out clone. The knock out clone exhibited a significantly reduced migration and proliferation ability when compared to the wildtype.ConclusionsITGB6 is a relevant factor in the progression of OSCC and can be used for the development of novel treatment strategies. The present study is the first to establish a monoclonal CRISPR/Cas9-mediated ITGB6 knockout cell clone derived from an OSCC cell line. It suggests that ITGB6 has a significant impact on the proliferative and migratory capacity in vitro.
Prevalence and barriers to early initiation of breastfeeding among urban poor full-time readymade garments working mothers: a mixed-methods study in Bangladesh
Authors: Islam Md. Rabiul , Tamanna Tasnim , Mohsin Nusrat Azrin , Tanha Arifa Farzana , Sheba Nusrat Hossain , Hannan JMA 
Published: June 2024

Abstract
Background
Early initiation of breastfeeding is the initiation of breastfeeding within one hour of birth, which plays a significant role in a born baby’s growth and survival, however its prevalence and predictors among urban full-time readymade garments (RMG) working mothers are not investigated. The purpose of this study is to determine the prevalence and factors affecting early initiation of breastfeeding among urban RMG working mothers.

Methods
A sequential explanatory mixed-methods study was conducted between March 2023 and December 2023 in Dhaka, Bangladesh. A total of 452 full-time female RMG workers were included for the quantitative study. Qualitative study was carried out among 30 full-time female RMG workers, four female physicians who were employed in the RMGs, four RMG factory managers, and four local pediatricians.

Results
The prevalence of early initiation of breastfeeding was 40% among the women. It was significantly associated with various factors, including socio-cultural barriers, the advanced age of the mother (AOR 3.93, 95%CI 1.18, 13.04), lack of education (AOR 6.86, 95%CI 1.11, 42.49), lack of awareness, and cultural practices such as initiating goat milk and honey instead of breast milk. The absence of colostrum feeding (AOR 8.96, 95%CI 4.30, 18.70) and pre-lacteal feeding (AOR 0.06, 95%CI 0.03, 0.11) were significant baby feeding practice-related barriers to early initiation of breastfeeding. Maternal health factors, notably post-delivery sickness, cesarean delivery, and lack of breastmilk production, were revealed as a significant hindrance to the early initiation of breastfeeding explored from qualitative analysis. In addition, RMG factory-related factors that significantly affect early initiation of breastfeeding include a strong focus on production, a busy schedule, and a lack of initiative regarding the early initiation of breastfeeding.

Conclusions
The prevalence of early initiation of breastfeeding among RMG working women is poor. This study emphasizes the need for interventions that address specific challenges of early initiation of breastfeeding faced by working mothers in RMG sectors, including improved lactation education, increased awareness to mitigate cultural barriers, RMG factory-based initiatives to empower female workers early initiation of breastfeeding, and preparing early initiation of breastfeeding -friendly post-cesarean unit at the health care facility.
Current situation of osteogenesis imperfecta in Spain: results from a Delphi study
Authors: Sagastizabal Belén , Calvo Inmaculada , Martínez-Ferrer Àngels , Clancy James , Pérez Álvaro , Gil Alicia , Bou Rosa 
Published: June 2024

AbstractBackgroundOsteogenesis imperfecta (OI) is a rare disease characterized by low bone mass and bone fragility, associated with an increased risk of fractures, and skeletal and extra-skeletal symptoms that results in an impairment of health-related quality of life of OI patients. Since published studies on OI in Spain are limited, this study aimed to determine the epidemiology, assessed the disease burden, management and unmet needs of OI patients in Spain. Thirty-four experts in the management of patients with osteogenesis imperfecta completed two rounds of online consultation and reported real-life experience and data from Spanish hospitals. Delphi study questionnaires were based on literature review. A working group of nationally recognized clinical experts supported the development of the study questionnaires and the final validation of results.ResultsThe estimated prevalence of patients diagnosed with OI in Spain is 0.56:10,000 inhabitants (95%CI: 0.54–0.59), which represents that, approximately, 2,669 OI patients are currently managed in Spanish hospitals. It is estimated that approximately 269 new patients would be diagnosed with OI each year in Spain, representing an estimated incidence of 0.06 (95%CI: 0.05–0.06) per 10,000 inhabitants per year. Clinical management of OI in Spain is performed by a range of medical specialists; however, multidisciplinary care is not fully implemented. The absence of an approved curative treatment or a treatment to reduce the clinical features of the disease remains the main unmet need.ConclusionsThis study provides a snapshot of the current situation of patients with OI in Spain reported by clinical experts. The results provide an estimation of the epidemiology of the disease, and complement the available evidence on disease burden, clinical management, and unmet needs of these patients in Spain.
Urolithin A promotes p62-dependent lysophagy to prevent acute retinal neurodegeneration
Authors: Jiménez-Loygorri Juan Ignacio , Viedma-Poyatos Álvaro , Gómez-Sintes Raquel , Boya Patricia 
Published: June 2024

Abstract
Background
Age-related macular degeneration (AMD) is the leading cause of blindness in elderly people in the developed world, and the number of people affected is expected to almost double by 2040. The retina presents one of the highest metabolic demands in our bodies that is partially or fully fulfilled by mitochondria in the neuroretina and retinal pigment epithelium (RPE), respectively. Together with its post-mitotic status and constant photooxidative damage from incoming light, the retina requires a tightly-regulated housekeeping system that involves autophagy. The natural polyphenol Urolithin A (UA) has shown neuroprotective benefits in several models of aging and age-associated disorders, mostly attributed to its ability to induce mitophagy and mitochondrial biogenesis. Sodium iodate (SI) administration recapitulates the late stages of AMD, including geographic atrophy and photoreceptor cell death.

Methods
A combination of in vitro, ex vivo and in vivo models were used to test the neuroprotective potential of UA in the SI model. Functional assays (OCT, ERGs), cellular analysis (flow cytometry, qPCR) and fine confocal microscopy (immunohistochemistry, tandem selective autophagy reporters) helped address this question.

Results
UA alleviated neurodegeneration and preserved visual function in SI-treated mice. Simultaneously, we observed severe proteostasis defects upon SI damage induction, including autophagosome accumulation, that were resolved in animals that received UA. Treatment with UA restored autophagic flux and triggered PINK1/Parkin-dependent mitophagy, as previously reported in the literature. Autophagy blockage caused by SI was caused by severe lysosomal membrane permeabilization. While UA did not induce lysosomal biogenesis, it did restore upcycling of permeabilized lysosomes through lysophagy. Knockdown of the lysophagy adaptor SQSTM1/p62 abrogated viability rescue by UA in SI-treated cells, exacerbated lysosomal defects and inhibited lysophagy.

Conclusions
Collectively, these data highlight a novel putative application of UA in the treatment of AMD whereby it bypasses lysosomal defects by promoting p62-dependent lysophagy to sustain proteostasis.

Graphical Abstract
Using GPT-4 to write a scientific review article: a pilot evaluation study
Authors: Wang Zhiping Paul , Bhandary Priyanka , Wang Yizhou , Moore Jason H. 
Published: June 2024

AbstractGPT-4, as the most advanced version of OpenAI’s large language models, has attracted widespread attention, rapidly becoming an indispensable AI tool across various areas. This includes its exploration by scientists for diverse applications. Our study focused on assessing GPT-4’s capabilities in generating text, tables, and diagrams for biomedical review papers. We also assessed the consistency in text generation by GPT-4, along with potential plagiarism issues when employing this model for the composition of scientific review papers. Based on the results, we suggest the development of enhanced functionalities in ChatGPT, aiming to meet the needs of the scientific community more effectively. This includes enhancements in uploaded document processing for reference materials, a deeper grasp of intricate biomedical concepts, more precise and efficient information distillation for table generation, and a further refined model specifically tailored for scientific diagram creation.
Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy
Authors: Song Pan , Gao Zirui , Bao Yige , Chen Li , Huang Yuhe , Liu Yanyan , Dong Qiang , Wei Xiawei 
Published: June 2024

AbstractThe Wnt/β-catenin signaling pathway plays a crucial role in various physiological processes, encompassing development, tissue homeostasis, and cell proliferation. Under normal physiological conditions, the Wnt/β-catenin signaling pathway is meticulously regulated. However, aberrant activation of this pathway and downstream target genes can occur due to mutations in key components of the Wnt/β-catenin pathway, epigenetic modifications, and crosstalk with other signaling pathways. Consequently, these dysregulations contribute significantly to tumor initiation and progression. Therapies targeting the Wnt/β-catenin signaling transduction have exhibited promising prospects and potential for tumor treatment. An increasing number of medications targeting this pathway are continuously being developed and validated. This comprehensive review aims to summarize the latest advances in our understanding of the role played by the Wnt/β-catenin signaling pathway in carcinogenesis and targeted therapy, providing valuable insights into acknowledging current opportunities and challenges associated with targeting this signaling pathway in cancer research and treatment.
Development of reciprocal connections between the dorsal lateral geniculate nucleus and the thalamic reticular nucleus
Authors: Campbell Peter W , Govindaiah Gubbi , Guido William 
Published: June 2024

AbstractThe thalamic reticular nucleus (TRN) serves as an important node between the thalamus and neocortex, regulating thalamocortical rhythms and sensory processing in a state dependent manner. Disruptions in TRN circuitry also figures prominently in several neurodevelopmental disorders including epilepsy, autism, and attentional defects. An understanding of how and when connections between TRN and 1st order thalamic nuclei, such as the dorsal lateral geniculate nucleus (dLGN), develop is lacking. We used the mouse visual thalamus as a model system to study the organization, pattern of innervation and functional responses between TRN and the dLGN. Genetically modified mouse lines were used to visualize and target the feedforward and feedback components of these intra-thalamic circuits and to understand how peripheral input from the retina impacts their development.Retrograde tracing of thalamocortical (TC) afferents through TRN revealed that the modality-specific organization seen in the adult, is present at perinatal ages and seems impervious to the loss of peripheral input. To examine the formation and functional maturation of intrathalamic circuits between the visual sector of TRN and dLGN, we examined when projections from each nuclei arrive, and used an acute thalamic slice preparation along with optogenetic stimulation to assess the maturation of functional synaptic responses. Although thalamocortical projections passed through TRN at birth, feedforward axon collaterals determined by vGluT2 labeling, emerged during the second postnatal week, increasing in density through the third week. Optogenetic stimulation of TC axon collaterals in TRN showed infrequent, weak excitatory responses near the end of week 1. During weeks 2–4, responses became more prevalent, grew larger in amplitude and exhibited synaptic depression during repetitive stimulation. Feedback projections from visual TRN to dLGN began to innervate dLGN as early as postnatal day 2 with weak inhibitory responses emerging during week 1. During week 2–4, inhibitory responses continued to grow larger, showing synaptic depression during repetitive stimulation. During this time TRN inhibition started to suppress TC spiking, having its greatest impact by week 4–6. Using a mutant mouse that lacks retinofugal projections revealed that the absence of retinal input led to an acceleration of TRN innervation of dLGN but had little impact on the development of feedforward projections from dLGN to TRN. Together, these experiments reveal how and when intrathalamic connections emerge during early postnatal ages and provide foundational knowledge to understand the development of thalamocortical network dynamics as well as neurodevelopmental diseases that involve TRN circuitry.
Minimally invasive stabilization using screws and cement for acetabular metastatic tumor: a case report
Authors: Chen Yang , Akbar Yunus , Xiang Haibin , Yadikan Yashengjiang , Cao Guoqing , Ju Xiaowei , Wu Xiaoguang , Wang Shiwen 
Published: June 2024

Abstract
Background
The aim of this case report is to evaluate minimally invasive stabilization using screws and cement for acetabular metastatic tumor and summarize the indications and contraindications for minimally invasive stabilization of acetabular metastatic tumors with screw and cement techniques.

Case presentation
Under imaging guidance, a patient with acetabular metastatic tumor was treated with hollow screw combined with bone cement fixation. Ischial screw, ascending branch screw, and anterior and posterior screws were inserted to firmly fix the anterior and posterior column of the acetabulum. At the same time, the third screw connected the anterior and posterior columns together, combined with bone cement into the fracture site to further increase local stability and resist bone defects caused by local tumor osteolysis. The patient was a 52-year-old Uygur male. Herein, we summarize his clinical symptoms and operation. Differences in visual analog scale and walking function (Musculoskeletal Tumor Society) before operation and at 2 months, 6 months, and 12 months after operation were compared.

Results
Postoperative complications and tumor progression were recorded. The patient was followed up for 16 months, and the operative time was 60 minutes. In total, 20 ml of bone cement was injected into the acetabular posterior column and the top of the acetabulum. VIsual analog scale score was 8 before operation, 3 at 2 months, 3 at 6 months, and 2 at 12 months after operation. Musculoskeletal Tumor Society function was 13 before operation, 23 at 2 months, 25 at 6 months, and 26 at 12 months after operation. During follow-up, no cement leakage, fever, hip nerve injury, pulmonary embolism, or imaging findings of further destruction of the acetabulum and surrounding bone were noted.

Conclusion
This case report shows that the treatment of acetabular metastatic cancer with minimally invasive stabilization using screws and cement under the C arm can effectively relieve pain and enhance the strength of the pelvis, and is innovative and feasible.