bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improve the cervical cancer prevention behaviors through mobile-based educational intervention based on I-CHANGE model: study protocol for a randomized controlled trial
Authors: Kazemi Sara , Zarei Fatemeh , Heidarnia Alireza , Alhani Fatemeh 
Published: September 2022

AbstractBackgroundApplications of mobile technologies (mHealth) have the potential to reduce health inequalities, give patients more control over their health, and improve health care’s cost-effectiveness. The widespread use of mobile phones offers us a new way to prevent cervical cancer. The objective of the study was to design and develop a mobile phone application (app) that aims to conduct a behavioral intervention for women and to evaluate the efficacy of the app-based intervention.MethodsThis study involves 5 phases. In the first phase, understanding women’s perspectives will be identified using a qualitative approach based on the I-Change model. In phase 2, the results from the qualitative approach and requirement prioritization through providing experts’ perspectives will be done. The main outputs of this phase will be resulted in prioritizing the main measurable effective variables of the I-Change model. Phase 3 will be processed for the development and psychometric of an assessment tool regarding selected constructs. In phase 4, the App framework and content development will be performed. In phase 5, a three-armed, parallel-design randomized controlled trial will be conducted on women. Two hundred ten women will be randomly assigned to three groups including two intervention groups and one control group. The intervention groups included the following: (1) a mobile application and (2) a digital book. The data will be evaluated using tools designed and constructed in phase 3 of the study at baseline in 3-month follow-up assessments. The impact of the two interventions on cervical cancer prevention behaviors through mobile-based educational intervention will then be evaluated.DiscussionA theory-based health education program using a mobile app to improve cervical cancer-preventive behaviors will be implemented for the first time in Iran. With an effective health mobile-based educational design, it is very important to determine whether Iranian women will be motivated to adhere to preventive behavior related to CC.Trial registrationIranian Clinical Trial Register IRCT20181205041861N3. Registered V2.0 on 26 October 2021.
Impact of emergency physician-performed ultrasound for the evaluation of patients with acute abdominal pain, prospective randomized dual Centre study: study protocol for a diagnostic trial
Authors: Brau François , Martin Stéphanie , Le Bastard Quentin , Ricaud Patricia , Legrand Arnaud , Montassier Emmanuel , Le Conte Philippe 
Published: September 2022

Abstract
Background
Abdominal pain is frequent in patients consulting in emergency departments. The aim of this study is to determine the diagnosis efficacy of point-of-care ultrasound (POCUS) in patients consulting in the ED for acute abdominal pain by comparing the rate of exact diagnostic between the two arms (with or without POCUS), according to the index diagnostic established by an adjudication committee.

Methods
It is a randomized, controlled, open and interventional study in two emergency departments. The included patients will be adults admitted for acute abdominal pain. Exclusion criteria will be a documented end-of-life, an immediate need of life-support therapy and pregnant or breast-feeding women. Patients will be randomized in intervention (POCUS) or control groups. POCUS will only be performed by trained physicians and will be added to the diagnosis procedure in the intervention group. In the control group, the diagnosis will be established after clinical examination and reception of biological analysis results. In the interventional group, the diagnosis will be established after a clinical exam, biological analysis reception and POCUS. An adjudication committee will review all data from case report forms and will determine the index diagnosis which will be used for the analysis.
The primary endpoint will be the comparison of the rate of exact diagnostic between the two arms according to the adjudication committee diagnostic. Secondary endpoints will be the comparison between the two groups for diagnostic delay, duration of ED stay, diagnostic performances for non-specific abdominal pain and hospitalization rate. The primary endpoint will be compared between the two groups using a mixed model taking into account the recruiting centre. Delays will be compared by a mixed linear generalized model. Diagnostic performances will be estimated with their 95% confidence intervals. For a correct diagnostic rate of 57% in the control group and 74% in the intervention group with a 0.05 alpha risk and a 80% power, 244 patients will be required.

Discussion
POCUS diagnostic abilities have been mainly demonstrated in monocentric studies but the level of evidence of its diagnostic efficacy remains controversial in particular in Europe. The aim of this study is to address this question with a rigorous methodology.

Trial registration
ClinicalTrials.gov NCT04912206. Registered on June 3, 2021.
Enhanced productivity of extracellular free fatty acids by gene disruptions of acyl-ACP synthetase and S-layer protein in Synechocystis sp. PCC 6803
Authors: Eungrasamee Kamonchanock , Lindblad Peter , Jantaro Saowarath 
Published: September 2022

Abstract
Background
Based on known metabolic response to excess free fatty acid (FFA) products, cyanobacterium Synechocystis sp. PCC 6803 preferentially both recycles via FFA recycling process and secrets them into medium. Engineered cyanobacteria with well growth and highly secreted FFA capability are considered best resources for biofuel production and sustainable biotechnology. In this study, to achieve the higher FFA secretion goal, we successfully constructs Synechocystis sp. PCC 6803 mutants disrupting genes related to FFA recycling reaction (aas gene encoding acyl–acyl carrier protein synthetase), and surface layer protein (encoded by sll1951).

Results
Three Synechocystis sp. PCC 6803 engineered strains, including two single mutants lacking aas (KA) and sll1951 (KS), and one double mutant lacking both aas and sll1951 (KAS), significantly secreted FFAs higher than that of wild type (WT). Certain increase of secreted FFAs was noted when cells were exposed to nitrogen-deficient conditions, BG11-half N and BG11-N conditions, with the exception of strain KS. Under BG11-N condition at day 10, strain KAS strikingly secreted FFAs products up to 40%w/DCW or 238.1 mg/L, with trace amounts of PHB. Unexpectedly, strain KS, with S-layer disruption, appeared to have endured longer in BG11-N growth medium. This strain KS significantly acclimated to the BG11-N environment by accumulating a greater glycogen pool with lower FFA production, whereas strain KA favored higher PHB and intracellular lipid accumulations with moderate FFA secretion.

Conclusions
Mutations of both aas and sll1951 genes in Synechocystis sp. PCC 6803 significantly improved the productivity of secreted FFAs, especially under nitrogen deprivation.
Intratumor heterogeneity and T cell exhaustion in primary CNS lymphoma
Authors: Heming Michael , Haessner Svea , Wolbert Jolien , Lu I-Na , Li Xiaolin , Brokinkel Benjamin , Müther Michael , Holling Markus , Stummer Walter , Thomas Christian , Schulte-Mecklenbeck Andreas , de Faria Flavia , Stoeckius Marlon , Hailfinger Stephan , Lenz Georg , Kerl Kornelius , Wiendl Heinz , Meyer zu Hörste Gerd , Grauer Oliver M. 
Published: September 2022

Abstract
Background
Primary central nervous system lymphoma (PCNSL) is a rare lymphoma of the central nervous system, usually of diffuse large B cell phenotype. Stereotactic biopsy followed by histopathology is the diagnostic standard. However, limited material is available from CNS biopsies, thus impeding an in-depth characterization of PCNSL.

Methods
We performed flow cytometry, single-cell RNA sequencing, and B cell receptor sequencing of PCNSL cells released from biopsy material, blood, and cerebrospinal fluid (CSF), and spatial transcriptomics of biopsy samples.

Results
PCNSL-released cells were predominantly activated CD19+CD20+CD38+CD27+ B cells. In single-cell RNA sequencing, PCNSL cells were transcriptionally heterogeneous, forming multiple malignant B cell clusters. Hyperexpanded B cell clones were shared between biopsy- and CSF- but not blood-derived cells. T cells in the tumor microenvironment upregulated immune checkpoint molecules, thereby recognizing immune evasion signals from PCNSL cells. Spatial transcriptomics revealed heterogeneous spatial organization of malignant B cell clusters, mirroring their transcriptional heterogeneity across patients, and pronounced expression of T cell exhaustion markers, co-localizing with a highly malignant B cell cluster.

Conclusions
Malignant B cells in PCNSL show transcriptional and spatial intratumor heterogeneity. T cell exhaustion is frequent in the PCNSL microenvironment, co-localizes with malignant cells, and highlights the potential of personalized treatments.
Gait parameters when walking with or without rollator on different surface characteristics: a pilot study among healthy individuals
Authors: Ekvall Hansson Eva , Akar Yara , Liu Tingting , Wang Cong , Malmgren Fänge Agneta 
Published: September 2022

AbstractObjectivesGait parameters can measure risks of falling and mortality and identify early stages of frailty. The use of walking aid changes gait parameters. The aim of this study was to describe differences in gait parameters among healthy adults when walking on different surfaces and under different conditions, with and without a rollator.ResultsTen healthy participants walked first without and then with a rollator upslope, downslope and on flat surface, on bitumen and gravel respectively. Step length, walking speed and sideway deviation was measured using an inertial measurement unit. Walking up a slope using a rollator generated the longest step length and walking down a slope using a rollator the shortest. Fastest walking speed was used when walking up a slope with rollator and slowest when walking down a slope with rollator. Sideway deviation was highest when walking down a slope and lowest when walking on gravel, both without rollator. Highest walk ratio was found when walk up a slope without rollator and lowest when walking down a slope with rollator. Data from this study provides valuable knowledge regarding gait parameters among healthy individuals, useful for future clinical research relevant for rehabilitation and public health.
Associated changes in stiffness of collagen scaffolds during osteoblast mineralisation and bone formation
Authors: Bakkalci Deniz , Micalet Auxtine , Al Hosni Rawiya , Moeendarbary Emad , Cheema Umber 
Published: September 2022

Abstract
Objective
Engineering bone in 3D is important for both regenerative medicine purposes and for the development of accurate in vitro models of bone tissue. The changing material stiffness of bone tissue had not yet been monitored throughout the process of mineralisation and bone nodule formation by osteoblasts either during in vitro engineering or in development perspective.

Results
Within this short research note, stiffness changes (Young’s modulus) during in vitro bone formation by primary osteoblasts in dense collagen scaffolds were monitored using atomic force microscopy. Data analysis revealed significant stiffening of 3D bone cultures at day 5 and 8 that was correlated with the onset of mineral deposition (p < 0.00005).
Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer
Authors: Li Peilong , Liu Shibiao , Du Lutao , Mohseni Ghazal , Zhang Yi , Wang Chuanxin 
Published: September 2022

AbstractLung cancer (LC) is the main cause of cancer-related mortality. Most LC patients are diagnosed in an advanced stage when the symptoms are obvious, and the prognosis is quite poor. Although low-dose computed tomography (LDCT) is a routine clinical examination for early detection of LC, the false-positive rate is over 90%. As one of the intensely studied epigenetic modifications, DNA methylation plays a key role in various diseases, including cancer and other diseases. Hypermethylation in tumor suppressor genes or hypomethylation in oncogenes is an important event in tumorigenesis. Remarkably, DNA methylation usually occurs in the very early stage of malignant tumors. Thus, DNA methylation analysis may provide some useful information about the early detection of LC. In recent years, liquid biopsy has developed rapidly. Liquid biopsy can detect and monitor both primary and metastatic malignant tumors and can reflect tumor heterogeneity. Moreover, it is a minimally invasive procedure, and it causes less pain for patients. This review summarized various liquid biopsies based on DNA methylation for LC. At first, we briefly discussed some emerging technologies for DNA methylation analysis. Subsequently, we outlined cell-free DNA (cfDNA), sputum, bronchoalveolar lavage fluid, bronchial aspirates, and bronchial washings DNA methylation-based liquid biopsy for the early detection of LC. Finally, the prognostic value of DNA methylation in cfDNA and sputum and the diagnostic value of other DNA methylation-based liquid biopsies for LC were also analyzed.
Higher levels of myelin are associated with higher resistance against tau pathology in Alzheimer’s disease
Authors: Rubinski Anna , Franzmeier Nicolai , Dewenter Anna , Luan Ying , Smith Ruben , Strandberg Olof , Ossenkoppele Rik , Dichgans Martin , Hansson Oskar , Ewers Michael ,   the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: September 2022

AbstractBackgroundIn Alzheimer’s disease (AD), fibrillar tau initially occurs locally and progresses preferentially between closely connected regions. However, the underlying sources of regional vulnerability to tau pathology remain unclear. Previous brain-autopsy findings suggest that the myelin levels—which differ substantially between white matter tracts in the brain—are a key modulating factor of region-specific susceptibility to tau deposition. Here, we investigated whether myelination differences between fiber tracts of the human connectome are predictive of the interregional spreading of tau pathology in AD.MethodsWe included two independently recruited samples consisting of amyloid-PET-positive asymptomatic and symptomatic elderly individuals, in whom tau-PET was obtained at baseline (ADNI:n = 275; BioFINDER-1:n = 102) and longitudinally in a subset (ADNI:n = 123, mean FU = 1.53 [0.69–3.95] years; BioFINDER-1:n = 39, mean FU = 1.87 [1.21–2.78] years). We constructed MRI templates of the myelin water fraction (MWF) in 200 gray matter ROIs and connecting fiber tracts obtained from adult cognitively normal participants. Using the same 200 ROI brain-parcellation atlas, we obtained tau-PET ROI values from each individual in ADNI and BioFINDER-1. In a spatial regression analysis, we first tested the association between cortical myelin and group-average tau-PET signal in the amyloid-positive and control groups. Secondly, employing a previously established approach of modeling tau-PET spreading based on functional connectivity between ROIs, we estimated in a linear regression analysis, whether the level of fiber-tract myelin modulates the association between functional connectivity and longitudinal tau-PET spreading (i.e., covariance) between ROIs.ResultsWe found that higher myelinated cortical regions show lower tau-PET uptake (ADNI: rho =  − 0.267,p < 0.001; BioFINDER-1: rho =  − 0.175,p = 0.013). Fiber-tract myelin levels modulated the association between functional connectivity and tau-PET spreading, such that at higher levels of fiber-tract myelin, the association between stronger connectivity and higher covariance of tau-PET between the connected ROIs was attenuated (interaction fiber-tract myelin × functional connectivity: ADNI:β =  − 0.185,p < 0.001; BioFINDER-1:β =  − 0.166,p < 0.001).ConclusionHigher levels of myelin are associated with lower susceptibility of the connected regions to accumulate fibrillar tau. These results enhance our understanding of brain substrates that explain regional variation in tau accumulation and encourage future studies to investigate potential underlying mechanisms.
Impact of Litsea cubeba inter-row cover on the structure of bacterial community in the tea plantation
Authors: Hao Hai-Ping , Xia Fei , Bai Hong-Tong , Yan Xun-you , Cui Hong-xia , Xie Xiao-ming , Shi Lei 
Published: September 2022

Abstract
Purpose
The application of bio-control plants in the agricultural processes is one of the effective ways to solve the traditional agricultural synthetic pesticide residues. This study will investigate the effect of bio-control plant Litsea cubeba branch inter-row cover on soil bacterial community, soil-enriched metabolites, and soil mineral nutrition in tea plantation, which will provide a basis for the use of bio-control plant in agroecological farming systems.

Methods
The fruit-bearing (F-Pr) and vegetative (F-Ab) branches of Litsea cubeba were inter-row covered (the use of plants for partial coverage of soil between the rows) in the tea plantation. And we determined the soil microbial community, soil mineral nutriment, and soil-enriched metabolites composition with the methods of 16S rRNA gene sequencing, inductively coupled plasma-atomic emission spectroscopy (ICP-AEC), inductively coupled plasma-optical emission spectrometry (ICP-OES), and gas chromatography-mass spectrometry (GS-MS). We also predict the function of soil bacteria with the Tax4Fun software.

Results
Litsea cubeba inter-row cover modified the soil microbial structure and diversity; Litsea cubeba inter-row cover significantly decreased the relative abundance of Acidobacteria, Chloroflexi, and Planctomycetes while increased the relative abundance of Proteobacteria. Litsea cubeba inter-row cover significantly antagonized the plant pathogen community, and its OTUs number decreased from 907 ± 81 in the control to 337 ± 25 in F-Pr treatment; compared with F-Pr treatment, F-Ab treatment had weaker effect on the abundance of nutrition metabolism and transport, carbohydrate utilization, and nitrate reduction A. The aluminum element in the F-Pr treatment was significantly reduced, while phosphorus was increased. The soil-enriched metabolites of F-Pr treatment contained some antibacterial substance, including 14.2 ± 3.32% citronellol, 10.38 ± 4.79% alpha-terpineol, and 8.25 ± 2.62% (+)-2-bornanone, which was the main environment factor that affects the soil bacterial structure and diversity.

Conclusion
Litsea cubeba inter-row cover significantly affected bacterial structure and diversity, slightly increased the soil pH, and improved soil aluminum and phosphorus status; soil-enriched metabolites were the major environment factor affecting soil bacterial community and should be considered in the application of bio-control plants; Litsea cubeba vegetative branch inter-row cover will be a feasible measure for integrated pest management in tea plantation.
Effectiveness and safety of lanadelumab in ethnic and racial minority subgroups of patients with hereditary angioedema: results from phase 3 studies
Authors: Craig Timothy J. , Zaragoza-Urdaz Rafael H. , Li H. Henry , Yu Ming , Ren Hong , Juethner Salomé , Anderson John ,   the HELP and HELP OLE Study Investigators
Published: September 2022

Abstract
Background
The COVID-19 pandemic has highlighted disparities in healthcare, particularly in the United States, even though disparities have existed since the organization of the modern healthcare system. Recruitment of patients from racial and ethnic minority groups is often minimal in phase 3 clinical trials, and is further exacerbated in the case of trials for rare diseases such as hereditary angioedema (HAE). This can lead to a gap in the understanding of minority patients’ experiences with these diseases and their response to potential treatment options.

Methods
We reviewed data from phase 3 double-blind (HELP) and open-label extension (HELP OLE) trials of lanadelumab, a monoclonal antibody developed for long-term prophylaxis against attacks of HAE. Efficacy (attack rate reduction) and safety (adverse events) results from White patients were compared descriptively to those from Hispanic/Latino patients, Black/African Americans, and other minority Americans.

Results
Not surprisingly, few minorities were recruited across both studies: 9.5% Black, 2.4% Asian, and 7.1% Hispanic/Latino versus 88.1% White and 91.7% non-Hispanic/non-Latino received lanadelumab in HELP, and 4.7% Black, 0.9% Asian, 0.9% other, and 6.1% Hispanic/Latino versus 93.4% White and 93.4% non-Hispanic/non-Latino were enrolled in HELP OLE. Although these studies were conducted in the United States, Canada, Europe, and Jordan, all minorities were from the United States. Despite the number of minority patients being far less than expected for the population, there was no evidence that either efficacy or adverse event profiles differed between ethnic or racial groups.

Conclusions
The HELP and HELP OLE studies described herein recruited far fewer minorities than would be ideal to represent these populations. However, evidence suggests that the effectiveness and tolerance of lanadelumab are similar between the groups. Nonetheless, the disparity in recruitment into research for minorities has significant room for improvement.
Trial registration NCT02586805, registered 26 October 2015, https://clinicaltrials.gov/ct2/show/record/NCT02586805. NCT02741596, registered 18 April 2016, https://clinicaltrials.gov/ct2/show/NCT02741596.
Integration of ultrasonography training into undergraduate medical education: catch up with professional needs
Authors: Teichgräber Ulf , Ingwersen Maja , Ehlers Claudia , Mentzel Hans-Joachim , Redies Christoph , Stallmach Andreas , Behringer Wilhelm , Guntinas-Lichius Orlando 
Published: September 2022

Abstract
Objective
Ultrasonography (US) has become the first-line imaging modality even for physicians who are not imaging specialists. The progress has not yet been sufficiently considered in medical education. The aim was to develop a curriculum that integrates US as a compulsory part into medical education directly from the start, to build up professional competencies toward residency.

Methods
Development was based on Kern’s six-step approach to identify problems, specify needs, define goals, outline strategies, and propose methods.

Results
The proposed curriculum follows a spiral course within which students should pass through four levels of training with increasing complexity. Students will be asked to independently prepare for courses by using learning videos. On the first training level, US should be closely linked to anatomy and physiology courses. Competency-centered courses should be held in small groups. On the second level, in the third year of education, students will apply point-of-care ultrasonography concerning multiple medical disciplines. On the third level, they will select a compulsory course in a specialty of their choice, held at five consecutive dates. From then on, US will be conducted in patients. Finally, during the final year, students are expected to use US under pro-active supervision with a large degree of independence and confidence. Throughout the curriculum, the discipline of radiology combines vertically with foundational sciences and horizontally with other medical specialties.

Conclusion
The conceptual proposal for a longitudinal US curriculum presented here has been developed by radiologists to equip students with competencies needed for contemporary patient care.