bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methyl β-Cyclodextrin-sperm-mediated gene editing (MBCD-SMGE): a simple and efficient method for targeted mutant mouse production
Authors: Moradbeigi Parisa , Hosseini Sara , Salehi Mohammad , Mogheiseh Asghar 
Published: January 2024

Abstract
Background
Generating targeted mutant mice is a crucial technology in biomedical research. This study focuses on optimizing the CRISPR/Cas9 system uptake into sperm cells using the methyl β-cyclodextrin-sperm-mediated gene transfer (MBCD-SMGT) technique to generate targeted mutant blastocysts and mice efficiently. Additionally, the present study elucidates the roles of cholesterol and reactive oxygen species (ROS) in the exogenous DNA uptake by sperm.

Results
In this study, B6D2F1 mouse sperm were incubated in the c-TYH medium with different concentrations of MBCD (0, 0.75, 1, and 2 mM) in the presence of 20 ng/µl pCAG-eCas9-GFP-U6-gRNA (pgRNA-Cas9) for 30 min. Functional parameters, extracellular ROS, and the copy numbers of internalized plasmid per sperm cell were evaluated. Subsequently, in vitro fertilization (IVF) was performed and fertilization rate, early embryonic development, and transfection rate were assessed. Finally, our study investigated the potential of the MBCD-SMGT technique in combination with the CRISPR-Cas9 system, referred to as MBCD-SMGE (MBCD-sperm-mediated gene editing), for generating targeted mutant blastocysts and mice. Results indicated that cholesterol removal from the sperm membrane using MBCD resulted in a premature acrosomal reaction, an increase in extracellular ROS levels, and a dose-dependent influence on the copy numbers of the internalized plasmids per sperm cell. Moreover, the MBCD-SMGT technique led to a larger population of transfected motile sperm and a higher production rate of GFP-positive blastocysts. Additionally, the current study validated the targeted indel in blastocyst and mouse derived from MBCD-SMGE technique.

Conclusion
Overall, this study highlights the significant potential of the MBCD-SMGE technique for generating targeted mutant mice. It holds enormous promise for modeling human diseases and improving desirable traits in animals.

Graphical Abstract
ECDEP: identifying essential proteins based on evolutionary community discovery and subcellular localization
Authors: Ye Chen , Wu Qi , Chen Shuxia , Zhang Xuemei , Xu Wenwen , Wu Yunzhi , Zhang Youhua , Yue Yi 
Published: January 2024

AbstractBackgroundIn cellular activities, essential proteins play a vital role and are instrumental in comprehending fundamental biological necessities and identifying pathogenic genes. Current deep learning approaches for predicting essential proteins underutilize the potential of gene expression data and are inadequate for the exploration of dynamic networks with limited evaluation across diverse species.ResultsWe introduce ECDEP, an essential protein identification model based on evolutionary community discovery. ECDEP integrates temporal gene expression data with a protein–protein interaction (PPI) network and employs the 3-Sigma rule to eliminate outliers at each time point, constructing a dynamic network. Next, we utilize edge birth and death information to establish an interaction streaming source to feed into the evolutionary community discovery algorithm and then identify overlapping communities during the evolution of the dynamic network. SVM recursive feature elimination (RFE) is applied to extract the most informative communities, which are combined with subcellular localization data for classification predictions.We assess the performance of ECDEP by comparing it against ten centrality methods, four shallow machine learning methods with RFE, and two deep learning methods that incorporate multiple biological data sources onSaccharomyces. Cerevisiae (S. cerevisiae),Homo sapiens (H. sapiens),Mus musculus, andCaenorhabditis elegans. ECDEP achieves an AP value of 0.86 on theH. sapiensdataset and the contribution ratio of community features in classification reaches 0.54 on theS. cerevisiae(Krogan) dataset.ConclusionsOur proposed method adeptly integrates network dynamics and yields outstanding results across various datasets. Furthermore, the incorporation of evolutionary community discovery algorithms amplifies the capacity of gene expression data in classification.
Prevalence of depression, anxiety, and stress and associated reasons among Iranian primary healthcare workers: a mixed method study
Authors: Kakemam Edris , Maassoumi Katayoun , Azimi Somayeh , Abbasi Madineh , Tahmasbi Fateme , Alizadeh Mahasti 
Published: January 2024

Abstract
Background
Different mental disorders may be associated with many work-related factors to which primary health care workers (PHCWs) are exposed. The current research aims to measure the rates of depression, anxiety, and stress among PHCWs, and their associated causes in primary health care (PHC) settings.

Methods
An explanatory sequential mixed methods design was employed in this research from January 2021 to January 2022 in Tabriz, Iran’s PHC centers. First, this study followed an online-based cross-sectional survey using a self-reported questionnaire. The Depression, Anxiety and Stress Scale-21 Items (DASS-21) and questions on demographic and work-related characteristics were completed by 303 frontline PHCWs during the quantitative phase. In the qualitative phase, a semi-structured interview was held with 12 PHCWs who had the highest level of depression, anxiety, and stress to identify the reasons and sources of mental health prevalence. Quantitative data were analyzed using descriptive statistics via SPSS-26. A content analysis was performed to analyze qualitative data.

Results
The results showed that self-reported stress, anxiety, and depression had a prevalence of 40.3%, 42.9%, and 42.6%, respectively. Symptoms of at least one mental disorder were experienced by 54% of respondents, while 28% had all three. Major sources of stress, anxiety, and depression among PHCWs were working environment conditions, organizational policies, job-related reasons, and interpersonal relations.

Conclusions
The results of current study indicated that PHCWs experienced high levels of depression, anxiety, and stress. The main factors and reasons that contributed to these mental health issues among PHCWs were work environment conditions, organizational policies, job-related reasons and interpersonal relations. Therefore, interventions should be implemented to promote mental health of PHCWs. This can include measures such as psychological screening, supportive care, workload management, flexible scheduling, and access to mental health resources. Additionally, training programs can be implemented to enhance resilience and coping skills among healthcare professionals.
Myth or fact: 3D-printed off-the-shelf prosthesis is superior to titanium mesh cage in anterior cervical corpectomy and fusion?
Authors: He Haoyu , Fan Lei , Lü Guohua , Li Xinyi , Li Yunchao , Zhang Ou , Chen Zejun , Yuan Hui , Pan Changyu , Wang Xiaoxiao , Kuang Lei 
Published: January 2024

Abstract
Background
To find out if three-dimensional printing (3DP) off-the-shelf (OTS) prosthesis is superior to titanium mesh cages in anterior cervical corpectomy and fusion (ACCF) when treating single-segment degenerative cervical spondylotic myelopathy (DCSM).

Methods
DCSM patients underwent ACCF from January 2016 to January 2019 in a single center were included. Patients were divided into the 3DP group (28) and the TMC group (23). The hospital stays, operation time, intraoperative blood loss, and the cost of hospitalization were compared. The Japanese Orthopedic Association (JOA) scores and Neck Disability Index (NDI) were recorded pre-operatively, 1 day, 3, 6, 12, and 24 months post-operatively. Radiological data was measured to evaluate fusion, subsidence, and cervical lordosis. Patients were sent with SF-36 to assess their health-related quality of life (HRQoL).

Results
The differences in operative time, intraoperative blood loss, and hospital stay were not statistically significant between groups (p > 0.05). Postoperative dysphagia occurred in 2 cases in the 3DP group and 3 cases in the TMC group, which all relieved one week later. The difference in improvement of JOA and NDI between the two groups was not statistically significant (p > 0.05). No hardware failure was found and bony fusion was achieved in all cases except one in the 3DP group. The difference in cervical lordosis (CL), fused segmental angle (FSA), mean vertebral height (MVH), and subsidence rates between groups at each follow-up time point was not statistically significant and the results of the SF-36 were similar (p > 0.05). The total cost was higher in the 3DP group with its higher graft cost (p < 0.05).

Conclusion
In treating single-segment DCSM with ACCF, both 3DP OTS prosthesis and TMC achieved satisfactory outcomes. However, the more costly 3DP OTS prosthesis was not able to reduce subsidence as it claimed.
Effect of the Japanese medical office system on job satisfaction, loyalty, engagement, and organizational commitment of medical practitioners: a survey of cardiologists in the acute care setting
Authors: Hashimoto Satoru , Motozawa Yoshihiro , Mano Toshiki 
Published: January 2024

Abstract
Background
In Japan, medical doctors have traditionally been assigned from university medical offices, under the medical office system. The present study examined the effects of the medical office system on job satisfaction, engagement, loyalty, and organizational commitment among cardiologists.

Methods
In this study, a survey of 156 cardiologists was conducted, from April 22, 2023, to May 21, 2023, to examine the effect of the medical office system on employee job satisfaction, employee engagement, and organizational commitment.

Results
Compared with the group that belonged to a medical office system (affiliated group, n = 117), the group that did not belong to a medical office system (non-affiliated group, n = 39) was affiliated to hospitals with a smaller number of beds. The results of the factor analysis showed that four types of hospital management styles were generated, namely, environment-, loyalty-building-, treatment-, and philosophy-oriented hospitals. There is an indication that the philosophy-oriented management style was adopted at the workplaces of the non-affiliated group. The treatment-oriented style also tended to be higher in the non-affiliated group than in the affiliated group. Furthermore, the non-affiliated group had higher organizational commitment, indicating that they were more likely to agree with the management philosophy set forth by hospital executives.

Conclusion
Although the medical office system did not affect job satisfaction, compared with medical doctors with the affiliated group, those with the non-affiliated group tended to work in hospitals that emphasized philosophy-oriented management, and they received moderate compensation while practicing in an environment suitable for their specialty. These results suggest that the medical office system makes it difficult for medical doctors to have high workplace loyalty, engagement, and commitment to the hospital to which they are dispatched.
A dry polymer nanocomposite transcutaneous electrode for functional electrical stimulation
Authors: Marquez-Chin Melissa , Saadatnia Zia , Sun Yu-Chen , Naguib Hani E. , Popovic Milos R. 
Published: January 2024

Abstract
Background
Functional electrical stimulation (FES) can be used in rehabilitation to aid or improve function in people with paralysis. In clinical settings, it is common practice to use transcutaneous electrodes to apply the electrical stimulation, since they are non-invasive, and can be easily applied and repositioned as necessary. However, the current electrode options available for transcutaneous FES are limited and can have practical disadvantages, such as the need for a wet interface with the skin for better comfort and performance. Hence, we were motivated to develop a dry stimulation electrode which could perform equivalently or better than existing commercially available options.

Methods
We manufactured a thin-film dry polymer nanocomposite electrode, characterized it, and tested its performance for stimulation purposes with thirteen healthy individuals. We compared its functionality in terms of stimulation-induced muscle torque and comfort level against two other types of transcutaneous electrodes: self-adhesive hydrogel and carbon rubber. Each electrode type was also tested using three different stimulators and different intensity levels of stimulation.

Results
We found the proposed dry polymer nanocomposite electrode to be functional for stimulation, as there was no statistically significant difference between its performance to the other standard electrodes. Namely, the proposed dry electrode had comparable muscle torque generated and comfort level as the self-adhesive hydrogel and carbon rubber electrodes. From all combinations of electrode type and stimulators tested, the dry polymer nanocomposite electrode with the MyndSearch stimulator had the most comfortable average rating.

Conclusions
The dry polymer nanocomposite electrode is a durable and flexible alternative to existing self-adhesive hydrogel and carbon rubber electrodes, which can be used without the addition of a wet interfacing agent (i.e., water or gel) to perform as well as the current electrodes used for stimulation purposes.
JAK/STAT in leukemia: a clinical update
Authors: Liang Dong , Wang Qiaoli , Zhang Wenbiao , Tang Hailin , Song Cailu , Yan Zhimin , Liang Yang , Wang Hua 
Published: January 2024

AbstractOver the past three decades, considerable efforts have been expended on understanding the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following the identification of the JAK2V617F mutation in myeloproliferative neoplasms (MPNs). The aim of this review is to summarize the latest progress in our understanding of the involvement of the JAK/STAT signaling pathway in the development of leukemia. We also attempt to provide insights into the current use of JAK/STAT inhibitors in leukemia therapy and explore pertinent clinical trials in this field.
Translation and cross-cultural adaptation of an Arabic version of PROMIS® of dyspnea activity motivation, requirement item pool and sleep-related impairments item bank
Authors: Aldhahi Monira I. , Bakhsh Hadeel R. , Bin Sheeha Bodor H. , Alhasani Rehab 
Published: January 2024

Abstract
Background
Patient-Reported Outcomes Measurement Information System (PROMIS®) Dyspnea Activity Motivation & Requirement item pool and sleep related impairments (SRI) item bank are designed in assessing the impact of dyspnea and sleep and guiding patient management. However, to effectively utilize this tool in Arabic-speaking populations, it is essential to perform a thorough translation and cultural adaptation process. Therefore, the aim of the study is to translate and cross-culturally adapt the translated items of the PROMIS® dyspnea activity motivation and requirement and SRI into Arabic.

Methods
A universal approach to translation adopted from PROMIS guideline document for translation and cultural adaptation, and the Chronic Illness Therapy translation methodology. The forward translation step followed by back work translation and Harmonization and quality assurance. Cognitive interview and pilot testing was conducted among 30 Arabic respondents across 5 different countries of Arabic speaker to produce a single version for Arab countries.

Results
A successful translation and cross-cultural adaptation into Arabic was achieved while maintaining equivalency. The translation was clear and more colloquial sentences were semantically equivalent and easy to understand. Equivalence of meaning of PROMIS® dyspnea activity motivation, requirement and SRI were achieved. All items were appropriate, relevant to culture and it measured the same concept as the original items. In Items 2 of the dyspnea activity motivation related to leisure activity “shopping”, the term “catalog and website” was added instead of “catalog only” which makes item in line with the original source but more comprehensive and applicable to current shopping trends.

Conclusions
The PROMIS® dyspnea activity motivation, requirement items pool and SRI item bank are culturally and linguistically suitable to be used in Arab country. By extending the accessibility of this measure to Arabic-speaking population, this study contributes significantly to the advancement of management and patient-centered care in the region. Further studies are necessary to evaluate the psychometric properties of these instruments.
Integrinβ-1 in disorders and cancers: molecular mechanisms and therapeutic targets
Authors: Su Chen , Mo Jie , Dong Shuilin , Liao Zhibin , Zhang Bixiang , Zhu Peng 
Published: January 2024

AbstractIntegrinβ-1 (ITGB1) is a crucial member of the transmembrane glycoprotein signaling receptor family and is also central to the integrin family. It forms heterodimers with other ligands, participates in intracellular signaling and controls a variety of cellular processes, such as angiogenesis and the growth of neurons; because of its role in bidirectional signaling regulation both inside and outside the membrane, ITGB1 must interact with a multitude of substances, so a variety of interfering factors can affect ITGB1 and lead to changes in its function. Over the past 20 years, many studies have confirmed a clear causal relationship between ITGB1 dysregulation and cancer development and progression in a wide range of benign diseases and solid tumor types, which may imply that ITGB1 is a prognostic biomarker and a therapeutic target for cancer treatment that warrants further investigation. This review summarizes the biological roles of ITGB1 in benign diseases and cancers, and compiles the current status of ITGB1 function and therapy in various aspects of tumorigenesis and progression. Finally, future research directions and application prospects of ITGB1 are suggested.
Macrophage barrier in the tumor microenvironment and potential clinical applications
Authors: Ji Shuai , Shi Yuqing , Yin Bo 
Published: January 2024

AbstractThe tumor microenvironment (TME) constitutes a complex microenvironment comprising a diverse array of immune cells and stromal components. Within this intricate context, tumor-associated macrophages (TAMs) exhibit notable spatial heterogeneity. This heterogeneity contributes to various facets of tumor behavior, including immune response modulation, angiogenesis, tissue remodeling, and metastatic potential. This review summarizes the spatial distribution of macrophages in both the physiological environment and the TME. Moreover, this paper explores the intricate interactions between TAMs and diverse immune cell populations (T cells, dendritic cells, neutrophils, natural killer cells, and other immune cells) within the TME. These bidirectional exchanges form a complex network of immune interactions that influence tumor immune surveillance and evasion strategies. Investigating TAM heterogeneity and its intricate interactions with different immune cell populations offers potential avenues for therapeutic interventions. Additionally, this paper discusses therapeutic strategies targeting macrophages, aiming to uncover novel approaches for immunotherapy.
Blood pressure lowering enhances cerebrospinal fluid efflux to the systemic circulation primarily via the lymphatic vasculature
Authors: Jukkola Jari , Kaakinen Mika , Singh Abhishek , Moradi Sadegh , Ferdinando Hany , Myllylä Teemu , Kiviniemi Vesa , Eklund Lauri 
Published: January 2024

Abstract
Background
Inside the incompressible cranium, the volume of cerebrospinal fluid is directly linked to blood volume: a change in either will induce a compensatory change in the other. Vasodilatory lowering of blood pressure has been shown to result in an increase of intracranial pressure, which, in normal circumstances should return to equilibrium by increased fluid efflux. In this study, we investigated the effect of blood pressure lowering on fluorescent cerebrospinal fluid tracer absorption into the systemic blood circulation.

Methods
Blood pressure lowering was performed by an i.v. administration of nitric oxide donor (sodium nitroprusside, 5 µg kg−1 min−1) or the Ca2+-channel blocker (nicardipine hydrochloride, 0.5 µg kg−1 min−1) for 10, and 15 to 40 min, respectively. The effect of ﻿blood pressure lowering on cerebrospinal fluid clearance was investigated by measuring the efflux of fluorescent tracers (40 kDa FITC-dextran, 45 kDa Texas Red-conjugated ovalbumin) into blood and deep cervical lymph nodes. The effect of nicardipine on cerebral hemodynamics was investigated by near-infrared spectroscopy. The distribution of cerebrospinal fluid tracers (40 kDa horse radish peroxidase,160 kDa nanogold-conjugated IgG) in exit pathways was also analyzed at an ultrastructural level using electron microscopy.

Results
Nicardipine and sodium nitroprusside reduced blood pressure by 32.0 ± 19.6% and 24.0 ± 13.3%, while temporarily elevating intracranial pressure by 14.0 ± 7.0% and 18.2 ± 15.0%, respectively. Blood pressure lowering significantly increased tracer accumulation into dorsal dura, deep cervical lymph nodes and systemic circulation, but reduced perivascular inflow along penetrating arteries in the brain. The enhanced tracer efflux by blood pressure lowering into the systemic circulation was markedly reduced (− 66.7%) by ligation of lymphatic vessels draining into deep cervical lymph nodes.

Conclusions
This is the first study showing that cerebrospinal fluid clearance can be improved with acute hypotensive treatment and that the effect of the treatment is reduced by ligation of a lymphatic drainage pathway. Enhanced cerebrospinal fluid clearance by blood pressure lowering may have therapeutic potential in diseases with dysregulated cerebrospinal fluid flow.
Genetic and clinical characterization of a novel FH founder mutation in families with hereditary leiomyomatosis and renal cell cancer syndrome
Authors: Sánchez-Heras Ana Beatriz , Dámaso Estela , Castillejo Adela , Robledo Mercedes , Teulé Alexandre , Lázaro Conxi , Sánchez-Martínez Rosario , Zúñiga Ángel , López-Fernández Adrià , Balmaña Judith , Robles Luis , Ramon y Cajal Teresa , Castillejo M. Isabel , Ibañez Raquel Perea , Sevila Carmen Martínez , Sánchez-Mira Andrea , Escandell Inés , Gómez Luís , Berbel Pere , Soto José Luis 
Published: January 2024

Abstract
Background
Hereditary leiomyomatosis and renal cell cancer syndrome is a rare autosomal dominant hereditary syndrome. Previously, we published the largest cohort of FH mutation carriers in Spain and observed a highly recurrent missense heterozygous variant, FH(NM_000143.4):c.1118A > G p.(Asn373Ser), in 104 individuals from 31 apparently unrelated families. Here, we aimed to establish its founder effect and characterize the associated clinical phenotype.

Results
Haplotype analysis confirmed that families shared a common haplotype (32/38 markers) spanning 0.61–0.82 Mb, indicating this recurrent variant was inherited from a founder ancestor. Cutaneous and uterine leiomyomatosis were diagnosed in 64.6% (64/99) and 98% (50/51) of patients, respectively, and renal cell cancer was present in 10.4% (10/96). The pathogenic FH_c.1118A > G variant is a Spanish founder mutation that originated 12–26 generations ago. We estimate that the variant may have appeared between 1370 and 1720. Individuals carrying this founder mutation had similar frequency of renal cell cancer and a higher frequency of renal cysts and leiomyomas than those in other cohorts of this syndrome.

Conclusions
In the Spanish province of Alicante there is a high prevalence of HLRCC because of the founder mutation FH c.1118A > G; p.(Asn373Ser). The characterization of founder mutations provides accurate and specific information regarding their penetrance and expressivity. In individuals with suspected HLRCC from the province of Alicante, genetic testing by direct analysis of the founder FH c.1118A > G; p.(Asn373Ser) mutation may be a faster and more efficient diagnostic tool compared with complete gene sequencing.