bluuebunny/crossref_metadata_2025 huggingface dataset:
A numerical investigation of blast-structure interaction effects on primary blast injury risk and the suitability of existing injury prediction methods
Authors: Denny Jack , Langdon Genevieve , Rigby Sam , Dickinson Alex , Batchelor James
Published: October 2022

Explosions increasingly occur in densely populated, urban locations. Primary blast injuries (PBIs), caused by exposure to blast wave overpressure, can be predicted using injury criteria, although many are based on idealised loading scenarios that do not necessarily reflect real life situations. At present, there is limited understanding of how, and to what extent, blast-structure interaction influences injury risk, and the suitability of injury criteria that assume idealised loading. This work employed computational fluid dynamics to investigate the influence of blast interaction effects such as shielding and channelling on blast load characteristics and predicted PBIs. The validated modelling showed that blast interaction with common urban features like walls and corners resulted in complex waveforms featuring multiple peaks and less clearly defined durations, and that these alter potential injury risk maps. For example, blast shielding due to corners reduced peak overpressures by 43%–60% at locations behind the corner. However, when the urban layout included a corner and a wall structure, higher pressures and impulse due to channelling were observed. The channelling significantly increased the injury risk at the exposed location and reduced the shielding effects behind the corner. In these cases, the application and interpretation of existing injury criteria had several limitations and reduced reliability. This demonstrates that structural-blast interaction from common urban layouts has a significant effect on PBI risk. Specific challenges and further work to develop understanding and reliability of injury prediction for urban blast scenarios are discussed.
A topic trend analysis on COVID-19 literature
Authors: Urru Sara , Sciannameo Veronica , Lanera Corrado , Salaris Silvano , Gregori Dario , Berchialla Paola
Published: October 2022

Objective

In the past 2 years, the number of scientific publications has grown exponentially. The COVID-19 outbreak hugely contributed to this dramatic increase in the volume of published research. Currently, text mining of the volume of SARS-CoV-2 and COVID-19 publications is limited to the first months of the outbreak. We aim to identify the major topics in COVID-19 literature collected from several citational sources and analyze the temporal trend from November 2019 to December 2021.

Methods

We performed an extensive literature search on SARS-Cov-2 and COVID-19 publications on PubMed, Scopus, and Web of Science (WoS) and a structural topic modelling on the retrieved abstracts. The temporal trend of the recognized topics was analyzed. Furthermore, a comparison between our corpus and the COVID-19 Open Research Dataset (CORD-19) repository was performed.

Results

We collected 269,186 publications and identified 10 topics. The most popular topic was related to the clinical pictures of the COVID-19 outbreak, which has a constant trend, and the least popular includes studies on COVID-19 literature and databases. “Telemedicine”, “Vaccine development”, and “Epidemiology” were popular topics in the early phase of the pandemic; increasing topics in the last period are “COVID-19 impact on mental health”, “Forecasting”, and “Molecular Biology”. “Education” was the second most popular topic, which emerged in September 2020.

Conclusions

We identified 10 topics for classifying COVID-19 research publications and estimated a nonlinear temporal trend that gives an overview of their unfolding over time. Several citational databases must be searched to retrieve a complete set of studies despite the efforts to build repositories for COVID-19 literature. Our collected data can help build a more focused literature search between November 2019 and December 2021 when carrying out systematic and rapid reviews and our findings can give a complete picture on the topic.
Federated learning for preserving data privacy in collaborative healthcare research
Authors: Loftus Tyler J , Ruppert Matthew M , Shickel Benjamin , Ozrazgat-Baslanti Tezcan , Balch Jeremy A , Efron Philip A , Upchurch Gilbert R , Rashidi Parisa , Tignanelli Christopher , Bian Jiang , Bihorac Azra
Published: October 2022

Generalizability, external validity, and reproducibility are high priorities for artificial intelligence applications in healthcare. Traditional approaches to addressing these elements involve sharing patient data between institutions or practice settings, which can compromise data privacy (individuals’ right to prevent the sharing and disclosure of information about themselves) and data security (simultaneously preserving confidentiality, accuracy, fidelity, and availability of data). This article describes insights from real-world implementation of federated learning techniques that offer opportunities to maintain both data privacy and availability via collaborative machine learning that shares knowledge, not data. Local models are trained separately on local data. As they train, they send local model updates (e.g. coefficients or gradients) for consolidation into a global model. In some use cases, global models outperform local models on new, previously unseen local datasets, suggesting that collaborative learning from a greater number of examples, including a greater number of rare cases, may improve predictive performance. Even when sharing model updates rather than data, privacy leakage can occur when adversaries perform property or membership inference attacks which can be used to ascertain information about the training set. Emerging techniques mitigate risk from adversarial attacks, allowing investigators to maintain both data privacy and availability in collaborative healthcare research. When data heterogeneity between participating centers is high, personalized algorithms may offer greater generalizability by improving performance on data from centers with proportionately smaller training sample sizes. Properly applied, federated learning has the potential to optimize the reproducibility and performance of collaborative learning while preserving data security and privacy.
Exploring the Relationship between Entrepreneurial Marketing Dimensions, Brand Equity and SME Growth
Authors: Hanaysha Jalal Rajeh
Published: October 2022

This study was conducted to test the linkages among the dimensions of entrepreneurial marketing, brand equity and business growth in small and medium enterprises (SMEs). Required data were gathered using the quantitative research approach. Particularly, the primary data were obtained through a structured survey from several owners and managers in SMEs. The obtained data were then analysed through SPSS and Partial-Least Square (PLS-SEM) approach to calculate the validity and reliability of the measurement items and also to verify the association among entrepreneurial marketing dimensions, brand equity and SME growth. The results showed that brand equity has a positive association with SME growth. The outcomes further indicated that customer intensity, value creation, innovativeness, resource leveraging, proactiveness and opportunity focus have positive effects on brand equity. However, the effect of risk taking on brand equity was found insignificant. This article addresses existing research gaps in the literature with regard to the linkages between entrepreneurial marketing dimensions, brand equity and SME growth.
Forecasting Undergraduate Majors: A Natural Language Approach
Authors: Lang David , Wang Alex , Dalal Nathan , Paepcke Andreas , Stevens Mitchell L.
Published: October 2022

Committing to a major is a fateful step in an undergraduate education, yet the relationship between courses taken early in an academic career and ultimate major issuance remains little studied at scale. Using transcript data capturing the academic careers of 26,892 undergraduates enrolled at a private university between 2000 and 2020, we describe enrollment histories by using natural-language methods and vector embeddings to forecast terminal major on the basis of course sequences beginning at college entry. We find that (a) a student’s very first enrolled course predicts their major 30 times better than random guessing and more than one-third better than majority-class voting, (b) modeling strategies substantially influence forecasting metrics, and (c) course portfolios vary substantially within majors, such that students with the same major exhibit relatively modest overlap.
(Un)claiming rights, resources, and ocean spaces: Marine genetic resources and area-based management tools in high seas governance negotiations
Authors: Melvin Emily C , Acton Leslie , Campbell Lisa M
Published: October 2022

After years of informal efforts, the parties to the United Nations Convention on the Law of the Sea (UNCLOS) are negotiating an international legally binding instrument to address governance gaps that have impeded attempts to conserve biodiversity in areas beyond national jurisdiction (ABNJ). Though these discussions were initiated in response to concerns about biodiversity, states have used them to advance competing claims regarding rights of access, ownership, and control of ocean spaces and resources. This paper examines how states have discussed ocean space in negotiations regarding area-based management tools (ABMTs) and marine genetic resources (MGRs) at the first three intergovernmental conferences regarding biodiversity in ABNJ. ABMTs, which have become widespread in governing ocean space for conservation, are premised on an ontological framing that ocean space can be divided by geographical boundaries into territories for management. MGRs, on the other hand, are newly recognized governance objects that cross existing spatial boundaries: between areas of national and international jurisdiction, between the seafloor and water column, and between the ocean and the laboratory. Through their mobility, MGRs reveal how territorial forms of governance over material resources intersect with other forms of exclusion, control, and rights-based institutions, suggesting the need to develop creative management regimes that go beyond territorial approaches.
Arrested Sensemaking: Typified Suppositions Sink the El Faro
Authors: Weick Karl E.
Published: October 2022

When a perceptual order is turned into a conceptual order a disjunction between continuity and discontinuity is created. Sensemaking to manage this disjunction often consists of attributions of typicality formed intuitively or through deliberation. The details lost during this process can lead to further breakdowns. This process of “arrested sensemaking” is illustrated with a disaster at sea when a 790-foot container ship, the El Faro, sailed into the eye of a category 3 hurricane and capsized. All 33 crew members perished. The prevailing sense was that the rough seas were a “typical” storm, arresting sensemaking in the face of a looming disaster.
ADAMTS13 conformation and immunoprofiles in Japanese patients with immune-mediated thrombotic thrombocytopenic purpura
Authors: Sakai Kazuya , Matsumoto Masanori , De Waele Laure , Dekimpe Charlotte , Hamada Eriko , Kubo Masayuki , Tersteeg Claudia , De Meyer Simon F. , Vanhoorelbeke Karen
Published: October 2022

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is an ultrarare thrombotic disease caused by autoantibody-induced ADAMTS13 deficiency. Open ADAMST13 conformation, induced by autoantibodies, was identified as a novel biomarker for iTTP. Determining immunoprofiles in patients with iTTP has been shown to guide the development of novel targeted therapies. However, these studies were done in mainly Caucasian iTTP cohorts. To validate those findings across other ethnic cohorts, we investigated 195 acute TTP plasma samples from the Japanese iTTP registry. Seventy-six of the 195 samples had detectable ADAMTS13 antigen levels, of which 94.7% were shown to have an open ADAMTS13 conformation. A positive correlation was observed between ADAMTS13 inhibitor titers (a diagnostic parameter in Japan) and anti-ADAMTS13 immunoglobulin G autoantibody titers. Studying anti-M, anti-DT, anti-CS, anti-T2-T5, anti-T6-T8, anti–CUB1-2 autoantibodies and the corresponding immunoprofile showed that 73% of the patients had anti-CS autoantibodies and 25.8% had anti-M autoantibodies, with the latter being higher than in Caucasians. Stratifying patients according to their immunoprofiles revealed that the profile with only anti-CS autoantibodies was the most common immunoprofile similar to that in Caucasians (28.9%). Although this profile did not affect the 1-year TTP-related mortality rate, patients with autoantibodies against all 6 ADAMTS13 fragments had a higher risk for TTP-related death than other patients (P = .02). We here validated open ADAMTS13 as a novel biomarker for acute iTTP and determined the dominant immunoprofiling in the Japanese cohort, contributing to setting up the diagnosis and managing guidelines across different ethnic cohorts and developing ADAMTS13 variants that do not bind to the anti-CS autoantibodies.
C9orf16 represents the aberrant genetic programs and drives the progression of PDAC
Authors: Chen Xiaojun , Zhang Hong , Xiao Bo
Published: October 2022

Background

Pancreatic ductal adenocarcinoma (PDAC), constituting 90% of pancreatic cancers, is the fourth leading cause of cancer-related deaths in the world. Lack of early detection of PDAC contributes to its poor prognosis as patients are often diagnosed at an advanced stage of disease. This is mostly due to the lack of promising diagnostic and therapeutic targets and corresponding drugs.

Methods and results

Here, by bioinformatic analysis of single cell RNA-sequencing data on normal pancreas tissues, primary and metastatic PDAC tumors, we identified a promising PDAC biomarker, C9orf16. The expression of C9orf16, rarely detectable in normal epithelial cells, was upregulated in primary PDAC cancer cells and was further elevated in metastatic PDAC cancer cells. Gain or loss of function of C9orf16 demonstrated its critical functions in regulating the cell proliferation, invasion and chemotherapy resistance of cancer cells. Pathway analysis and functional studies identified MYC signaling pathways as the most activated pathways in regulating C9orf16 expression and in mediating the development and progression of PDAC.

Conclusions

These data suggested a crucial gene regulation system, MYC-C9orf16, which is actively involved in PDAC development and progression, and targeting this system should be a novel diagnostic and therapeutic target for PDAC.
Study protocol for artificial intelligence-assisted sponge cytology as pre-endoscopy screening for early esophegeal squmaous epithelial lesions in China
Authors: Feng Yadong , Wang Bin , Pan Liang , Yao Bin , Deng Bin , Liang Yan , Sun Yongzhen , Zang Juncai , Xu Xinyi , Song Jie , Li Mengjie , Xu Guangpeng , Zhao Kai , Cheng Cui-E. , Shi Ruihua
Published: October 2022

Background

Endoscopic screening is the widely accepted screening strategy for esophageal squmaous cell carcinoma (ESCC). However, massive endoscopic screening is expensive and not cost-efficient, and novel pre-endoscopy detection used as a preliminary screening method arouses new concerns. We are planning to launch an artificial intelligence (AI) assisted sponge cytology for detecting esophageal squmaous high-grade intraepithelial neoplasia (HGIN) and above lesions. The aim of this trail is to investigate the efficiency of AI-assisted sponge cytology in population-based screening of early esophageal squmaous epithelial lesions.

Methods

The study will be prospectively conducted in five regions with a high prevalence of ESCC. AI-assisted sponge cytology and endoscopic examination will be sequentially performed. Based on our previous data, at least 864 patients with esophageal HGIN and above lesions are needed to achieve enough statistical power. And, a calculated 112,500 individuals with high risks of ESCC will be recruited. In the first stage, each 24,000 participants who meet the inclusion criteria will be recruited on a voluntary basis. Setting pathological results as standard reference, diagnostic threshold and according performance of AI-assisted detection will be evaluated. A prediction model will be constructed by co-analyzing cytological results and relevant risk factors. Then, an external validation cohort will be used for validation of the model efficiency. Also, cost-efficiency analysis will be performed. This study protocol was registered on chineseclinicaltrial.gov (ChiCTR1900028524).

Discussion

Our study will determine whether this AI-assisted sponge cytology can be used as an effective pre-endoscopy detection tool for large-scale screening for ESCC in high-risk areas.
Ergonomic and individual risk factors for musculoskeletal pain in the ageing workforce
Authors: Nygaard Niels-Peter Brøchner , Thomsen Gert Frank , Rasmussen Jesper , Skadhauge Lars Rauff , Gram Bibi
Published: October 2022

Background

The present study aimed to investigate the possible association between specific ergonomic and individual risk factors and musculoskeletal pain (MSP) in the back, shoulder, hip and knee region in workers aged 50-65y.

Methods

The study was a population based cross-sectional survey. The study population comprised citizens born between 1952–1966, living in Esbjerg municipality, Denmark, ultimo 2016 (n = 23,463). A questionnaire was sent electronically or by mail. The analysis included the working population only. A multivariate logistic regression was used for each of the following dependent variables; musculoskeletal pain for the past 3 months in the back, shoulder, hip and knee, where independent variables included ergonomic exposure, age, sex, body mass index (BMI) and leisure time physical activity (LTPA).

Results

The overall response rate was 58% and the data of individuals at work (n = 9,263) demonstrated several ergonomic exposures with increased odds for pain in specific regions. Exposure to back twisted or bend, squatting or lying on knees and to carrying or lifting were associated with musculoskeletal pain in the back, whereas exposure to back twisted or bend, arms above shoulder and repeated arm movement were associated with pain in the shoulder. Exposure to back twisted or bend, repeated arm movement, squatting or lying on knees and to carrying or lifting were associated with musculoskeletal pain in the hip. Important individual risk factors were also identified. Increasing age was significantly associated with increased pain in the hip but associated with less risk for pain in the back and shoulder. Males had higher odds for pain in the back and knee compared to females but lower odds for pain in the hip. BMI was particularly important for knee pain. The level of LTPA did not have an important association with MSP in any region.

Conclusion

There is a significant positive association between ergonomic exposures and musculoskeletal pain, which were specific for the back, shoulder, hip and knee. In addition, the data demonstrated a differential association with age, sex and BMI. This needs to be considered for the treatment and classification of musculoskeletal pain and for future preventive initiatives.
Finite element analyses of lateral condyle fracture fixation in paediatrics regarding configuration of Kirschner-wire
Authors: Jeon Sangbin , Ahn Wooyeol , Oh Jongbeom , Chung Jaiwoo , Choi Junwon , Lee Soonchul
Published: October 2022

Background

This study aimed to discover the most stable outcome among different Kirschner-wire (K-wire) configurations for fixation of a lateral condyle fracture (Milch type II) in different loads of stress by using finite element analyses (FEA).

Methods

The right humerus of a 6-year-old boy with a lateral condyle fracture (Milch type II), was modelled with a computer aided engineering. Using FEA, peak von Mises stress and stiffness were evaluated first for a single K-wire fixation by varying the angle (0, 5, 10, 15, 20, 25, 30 degrees). Then, based on the single K-wire result, assessment of peak von Mises stress and stiffness were evaluated via FEA for two- or three-wire fixation under various configurations (two convergent, two parallel, three divergent).

Results

Single K-wire fixation by 5 and 25 degrees had the lowest peak von Mises stress. The fracture site showed higher stiffness at 0, 5 and 15 degrees. Considering the collected results and clinical situation, 5 degree K-wire was selected for the FEA of multiple K-wire fixation. For multiple K-wire fixation, three divergent (5–20-35 degrees) K-wires showed better stability, both in peak von Mises stress and stiffness, than any two-K-wire configurations. Among two K-wire fixations, two divergent (5–50 degrees) K-wires provided the lowest von Mises stress in varus and valgus while two divergent (5–65 degrees) K-wires showed better results in flexion, extension, internal and external rotation, and both configurations showed similar results in stiffness.

Conclusions

We successfully created a paediatric lateral condyle fracture (Milch type II) model which was used to conduct FEA on different K-wire configurations to achieve stability of the fracture. Our results show that an initial K-wire inserted at 5 degrees, followed by the insertion of a second divergent wire at either 45 or 60 degrees provides the most stability in two K-wire fixations in this type of fracture repair.
Identification of a novel fully human anti-toxic shock syndrome toxin (TSST)-1 single-chain variable fragment antibody averting TSST-1-induced mitogenesis and cytokine secretion
Authors: Soezi Mahdieh , Piri-Gavgani Somayeh , Ghanei Mostafa , Omrani Mir Davood , Soltanmohammadi Behnoush , Bagheri Kamran Pooshang , Cohan Reza Ahangari , Vaziri Farzam , Siadat Seyed Davar , Fateh Abolfazl , Khatami Shohreh , Azizi Masoumeh , Rahimi-Jamnani Fatemeh
Published: October 2022

Background

Staphylococcal superantigens are virulence factors that help the pathogen escape the immune system and develop an infection. Toxic shock syndrome toxin (TSST)-1 is one of the most studied superantigens whose role in toxic shock syndrome and some particular disorders have been demonstrated. Inhibiting TSST-1 production with antibiotics and targeting TSST-1 with monoclonal antibodies might be one of the best strategies to prevent TSST-1-induced cytokines storm followed by lethality.

Results

A novel single-chain variable fragment (scFv), MS473, against TSST-1 was identified by selecting an scFv phage library on the TSST-1 protein. The MS473 scFv showed high affinity and specificity for TSST-1. Moreover, MS473 could significantly prevent TSST-1-induced mitogenicity (the IC50 value: 1.5 µM) and cytokine production.

Conclusion

Using traditional antibiotics with an anti-TSST-1 scFv as a safe and effective agent leads to deleting the infection source and preventing the detrimental effects of the toxin disseminated into the whole body.
An assessment of the impact of formal preparation activities on performance in the University Clinical Aptitude Test (UCAT): a national study
Authors: Kulkarni Sanat , Parry Jayne , Sitch Alice
Published: October 2022

Background

Previous studies have shown performance in the University Clinical Aptitude Test (UCAT) to be associated with measures of candidate socio-economic advantage such as parental occupation and type of school attended. It is possible that access to preparation support and materials may in part explain these associations. In this paper we determine whether use of formal preparation resources is associated with higher UCAT scores and whether differences in use of preparation resources exist between socio-demographic groups.

Methods

After completing the 2017 UCAT UK school-leaver candidates (n = 14,332) were asked to answer a questionnaire regarding their use of official UCAT and commercial resources, school-based support, and time spent preparing. Multiple linear and logistic regression models were used to evaluate the associations between preparedness, demographic characteristics and UCAT performance.

Results

Five thousand, four hundred thirty-nine (38%) candidates responded to the questionnaire. Use of freely available UCAT official practice tests, paid commercial materials, attendance at school-based preparation courses and spending more time preparing were significantly associated with higher UCAT scores. Candidates who were from less deprived backgrounds and attending independent or grammar schools were significantly more likely to use paid commercial materials and spend longer preparing.

Conclusions

Reported use of preparation resources varies between candidates from different socio-demographic backgrounds and is associated independently with performance in the UCAT. Increasing the availability of freely available resources may mitigate some of these differences.
Plasmodium falciparum community prevalence and health-seeking behaviours in rural Sussundenga District, Mozambique
Authors: Earland Dominique E. , Bibe Albino Francisco , Novela Anísio , Ferrão João , Searle Kelly M.
Published: October 2022

Background

Impacts of nationally directed malaria control interventions hinge on understanding malaria transmission and prevention at the community level. The decision to seek care or health-seeking behaviours provide valuable insight on knowledge of malaria, access to care, and efficacy of malaria case management. Thus far, few studies have focused on central Mozambique. The aim was to describe community level Plasmodium falciparum prevalence and health-seeking behaviours among residents of Sussundenga, Mozambique, a rural village in Manica Province with high malaria incidence reported at the Sussundenga-Sede health centre (RHC).

Methods

A cross-sectional community-based survey was conducted from December 2019 to February 2020. A random household sampling method was used, based on enumerated households from satellite imagery. All consenting participants completed a survey about malaria risk, prevention, and health-seeking behaviours, and received a P. falciparum malaria rapid diagnostic test (RDT).

Results

The study enrolled 358 individuals from 96 households. The P. falciparum prevalence was 31.6% (95% CI [26.6–36.5%]). Ninety-three percent of participants reported using the Sussundenga-Sede RHC for healthcare. Sixty-six percent of participants (N = 233) experienced at least one malaria symptom in the past month, with self-reported fever most frequently reported (19.3%). Of these, 176 (76.5%) sought care in a health facility and 174 (79%) received an RDT with 130 (63%) having a positive test. Of those with a positive RDT, 127 (97%) received artemether-lumefantrine. Following treatment, 123 (97%) participants’ symptoms resolved within a median of 3 days (IQR: 3–5) ranging from 2 to 14 days. In this high transmission setting, a high proportion of participants recognized malaria related symptoms then received a proper diagnostic test and treatment in a health facility.

Conclusions

Future interventions that leverage this health-seeking behaviour and strengthen health systems for community interventions will improve malaria control and inform the efficacy of potential interventions at this particular international border.
Tubulovillous adenoma with high-grade dysplasia of the vulva harboring high tumor mutational burden and cancer-associated mutations: a case report
Authors: Sato Hanako , Murakami Kosuke , Otani Tomoyuki , Matsumura Noriomi
Published: October 2022

Background

Vulvar cancer is a rare disease, accounting for approximately 5% of gynecological malignancies. Primary adenocarcinoma of intestinal-type of the vulva or its precancerous lesion is extremely rare, and details regarding its origin, evolution and related genetic mutations are unknown. Treatment options for this cancer have not been defined.

Case presentation

A 63-year-old Japanese woman came to the hospital because she was aware of a vulvar mass. There was a 1 cm mass on the dorsal side of the vulva, just outside the remains of the hymen. Biopsy revealed suspected adenocarcinoma, and wide local excision was performed. From histopathology and immunohistochemistry, the specimen was diagnosed as tubulovillous adenoma with high-grade dysplasia of the vulva. No other primary lesions were found, and the vulva was considered the primary site. A gene panel test (FoundationOneCDx assay) showed a high tumor mutational burden and mutations in TP53, KEL, RB1, RNF43, PTEN, GNAS, and PIK3CA.

Conclusions

The current case of tubulovillous adenoma with high-grade dysplasia of the vulva had a variety of cancer-associated mutations, despite being a precancerous lesion. In cases of intestinal-type neoplasms of the vulva, it may be helpful to check tumor mutational burden and gene mutations for treatment selection.
Deer antler extract promotes tibia fracture healing in mice by activating BMP-2/SMAD4 signaling pathway
Authors: Wang Jianyu , Wei Yuchi , Zhou Zhenwei , Yang Jie , Jia Yuyan , Wu Hailong , Dong Haisi , Leng Xiangyang
Published: October 2022

Background

Deer antler is a traditional Chinese medicine with the function of tonifying kidney and strengthening bone, which is often used to treat orthopedic diseases.

Methods

Eight-week-old C57BL/6 mice were used as the fixation model of open tibial fracture with intramedullary nail. The mice were treated with deer antler extract (DAE) or PBS by oral gavage once daily. The tibial fracture samples were collected and performed to the tissue analysis, including X-ray, micro-CT, histology, qRT-PCR, immunohistochemistry. MC3T3-E1 cells were used to detect the effect of deer antler extract on ability of cell proliferation and migration by CCK-8 assay and cell scratch test.

Results

Imaging and micro-CT showed that DAE could promote the healing of tibial fracture in mice, and histological analysis showed that DAE could promote the transformation of cartilage callus to bone callus in fracture area. The results of qRT-PCR and immunohistochemistry showed that DAE could promote intrachondral ossification in fracture zone and the mechanism of promoting fracture healing may be related to the activation of BMP-2/SMAD4 signaling pathway. In the cytological experiment of DAE, it can be found that DAE promoted the proliferation of MC3T3-E1 cells and the migration of MC3T3-E1 cells at a certain concentration, which is also related to the promotion of fracture healing by DAE.

Conclusion

DAE can promote fracture healing by activating BMP-2/SMAD4 signaling pathway. DAE has the potential to be used in clinic as an important means of promoting fracture healing.
Insulin-like peptide 5 (INSL5) positively correlates with anti-Müllerian hormone (AMH) in women with the polycystic ovary syndrome: a case-control study
Authors: Chen Yijie , Deng Miao , Chen Zhaojing , Han Shuyang , Chen Jun , Zhang Hongyan , Wang Qianwen , Jin Xuejing , Liu Wenhua , Zhang Zhifen
Published: October 2022

Background

Insulin-like peptide 5 (INSL5) is involved in both reproductive and metabolic processes in polycystic ovary syndrome (PCOS). This study aimed to evaluate the relationship between INSL5 and anti-Müllerian hormone (AMH).

Methods

A retrospective case–control study was conducted in a university-based reproductive centre between December 2019 and January 2021. We included 117 women with PCOS and 100 healthy subjects from Zhejiang Province. All subjects were divided into four groups (1st–4th) based on quartiles of serum INSL5 levels. Serum INSL5 concentration was assayed using an enzyme-linked immunosorbent assay.

Results

A significant direct association was observed between serum INSL5 and AMH levels in women with PCOS. The mean AMH level in the 1st–4th INSL5 level quartiles were 4.64, 5.20, 6.46, and 9.48 ng/ml, respectively (P < 0.001). After adjusting for age, body mass index, metabolic indices, and serum levels of oestradiol and total testosterone, AMH levels remained positively and significantly associated with INSL5 levels (P for trend < 0.001). The diagnostic value of AMH was better than that of INSL5.

Conclusions

INSL5 and AMH levels were significantly correlated and elevated in women with PCOS. INSL5 and AMH might be associated with increased androgen secretion and chronic anovulation in PCOS.
Association of cardiovascular health with diabetic complications, all-cause mortality, and life expectancy among people with type 2 diabetes
Authors: Zhang Yuan , Yang Rongrong , Hou Yabing , Chen Yanchun , Li Shu , Wang Yaogang , Yang Hongxi
Published: October 2022

Background

We aimed to assess the impact of healthy cardiovascular health (CVH) on diabetic complications, mortality, and life expectancy among people with type 2 diabetes and to explore whether inflammation marker mediate these associations.

Methods

This prospective cohort study included 33,236 participants (aged 40–72) with type 2 diabetes from the UK Biobank with annual follow-up from 2006 to 2010 to 2020. Type 2 diabetes was ascertained from self-report, glycated hemoglobin ≥ 6.5%, hospital inpatient registry, or glucose-lowering medication use. Information on mortality was derived from the national death registry. Favorable CVH metrics consisted of non-smoker, regular physical activity, a healthy diet, non-overweight, untreated resting blood pressure < 120/<80 mm Hg, and untreated total cholesterol < 200 mg/dL. Participants were categorized into three groups according to the number of favorable CVH metrics: unfavorable (0 or 1); intermediate (any 2 or 3); and favorable (4 or more). Inflammation marker, as measured by C-reactive protein (CRP), was assessed at baseline and categorized as low (≤ 3 mg/L) and high (> 3 mg/L). Data were analyzed using Cox regression models, flexible parametric survival models, and mediation models.

Results

During the follow-up (median: 11.7 years), 3133 (9.4%) cases of diabetes complications and 4701 (14.1%) deaths occurred. Compared to unfavorable CVH, favorable CVH was associated with a reduced risk of diabetes complications (HR, 0.35; 95% CI, 0.26–0.47) and all-cause mortality (HR, 0.53; 95% CI, 0.43–0.65). In participants with unfavorable CVH, life expectancy at age 45 had a significantly reduction of 7.20 (95% CI, 5.48–8.92) years compared to those with a favorable CVH. Among people with type 2 diabetes, the proportions of diabetes complications and all-cause mortality that would be reduced by promoting the favorable CVH was 61.5% and 39.1%, respectively. CRP level mediated 14.3% and 29.7% of the associations between CVH and diabetic complication and all-cause mortality, respectively.

Conclusion

A favorable CVH was associated with lower risk of diabetes complications and mortality risk, and was associated with a longer life expectancy among people with type 2 diabetes. This association may be in part accounted for by inflammatory processes. Our findings highlight the importance of favorable CVH for the prevention of diabetic complications and all-cause mortality among people with type 2 diabetes, and underscores the need to monitor inflammation among people with unfavorable CVH.
Diagnostic models for fever of unknown origin based on 18F-FDG PET/CT: a prospective study in China
Authors: Chen Jia , Xing MingYou , Xu Dong , Xie NaNa , Zhang WenCong , Ruan QiuRong , Song JianXin
Published: October 2022

Background

This study aims to analyze the 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) characteristics of different causes of fever of unknown origin (FUO) and identify independent predictors to develop a suitable diagnostic model for distinguishing between these causes. A total of 524 patients with classical FUO who underwent standard diagnostic procedures and PET/CT were prospectively studied. The diagnostic performance of PET/CT imaging was analyzed, and relevant clinical parameters that could improve diagnostic efficacy were identified. The model was established using the data of 369 patients and the other 155 patients comprised the validation cohort for verifying the diagnostic performance of the model.

Results

The metabolic characteristics of the “hottest” lesion, the spleen, bone marrow, and lymph nodes varied for various causes. PET/CT combined with clinical parameters achieved better discrimination in the differential diagnosis of FUO. The etiological diagnostic models included the following factors: multisite metabolic characteristics, blood cell counts, inflammatory indicators (erythrocyte sedimentation rate, C-reactive protein, serum ferritin, and lactate dehydrogenase), immunological indicators (interferon gamma release assay, antinuclear antibody, and anti-neutrophil cytoplasm antibody), specific signs (weight loss, rash, and splenomegaly), and age. In the testing cohort, the AUCs of the infection prediction model, the malignancy diagnostic model, and the noninfectious inflammatory disease prediction model were 0.89 (95% CI 0.86–0.92), 0.94 (95% CI 0.92–0.97), and 0.95 (95% CI 0.93–0.97), respectively. The corresponding AUCs for the validation cohort were 0.88 (95% CI 0.82–0.93), 0.93 (95% CI 0.89–0.98), and 0.95 (95% CI 0.92–0.99), respectively.

Conclusions

18F-FDG PET/CT has a certain level of sensitivity and accuracy in diagnosing FUO, which can be further improved by combining it with clinical parameters. Diagnostic models based on PET/CT show excellent performance and can be used as reliable tools to discriminate the cause of FUO.

Trial registration This study (a two-step method apparently improved the physicians’ level of diagnosis decision-making for adult patients with FUO) was registered on the website http://www.clinical-trials.gov on January 14, 2014, with registration number NCT02035670.
Radioimmunotherapy study of 131I-labeled Atezolizumab in preclinical models of colorectal cancer
Authors: Zhang Linhan , Zhao Sheng , Jiang Huijie , Zhang Rongjun , Zhang Mingyu , Pan Wenbin , Sun Zhongqi , Wang Dandan , Li Jinping
Published: October 2022

Background

Programmed cell death 1 ligand 1(PD-L1) is overexpressed in many tumors. The radionuclide-labeled anti-PD-L1 monoclonal antibody can be used for imaging and therapy of PD-L1 overexpressing cancer. Here, we described 131I-labeled Atezolizumab (131I-Atezolizumab, targeting PD-L1) as a therapeutic agent for colorectal cancer with PD-L1 overexpression.

Methods

131I-Atezolizumab was prepared by the Iodogen method. The expression levels of PD-L1 in different human colorectal cells were determined by flow cytometry, western blot and cell binding assay. The immunoreactivity of 131I-Atezolizumab to PD-L1 high-expressing cells was determined by immunoreactive fraction. The killing abilities of different concentrations of 131I-Atezolizumab on cells with high and low expression of PD-L1 were detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Cerenkov luminescence imaging (CLI) and radioimmunotherapy (RIT) of 131I-Atezolizumab were performed on two human colorectal cancer models. The distribution and tumor targeting of 131I-Atezolizumab were evaluated by imaging. Tumor volume and survival time were used as indicators to evaluate the anti-tumor effect of 131I-Atezolizumab.

Results

The expression level of PD-L1 in vitro determined by the cell binding assay was related to the data of flow cytometry and western blot. 131I-Atezolizumab can specifically bind to PD-L1 high-expressing cells in vitro to reflect the expression level of PD-L1. Immunoreactive fraction of PD-L1 high-expressing RKO cells with 131I-Atezolizumab was 52.2%. The killing ability of 131I-Atezolizumab on PD-L1 high-expressing cells was higher than that of low-expressing cells. CLI proved that the specific uptake level of tumors depends on the expression level of PD-L1. Effect of 131I-Atezolizumab RIT showed an activity-dependent tumor suppressor effect on RKO tumor-bearing mice with high PD-L1 expression. 131I-Atezolizumab (37 MBq) can improve the median survival time of mice (34 days), compared to untreated mice (27 days) (P = 0.027). Although a single activity(37 MBq) of 131I-Atezolizumab also inhibited the tumors of HCT8 tumor-bearing mice with low PD-L1 expression (P < 0.05), it could not prolong the survival of mice(P = 0.29).

Conclusion

131I-Atezolizumab can be used as a CLI agent for screening PD-L1 expression levels. It may be used as a radioimmunotherapy drug target for PD- L1 overexpressing tumors.
Etoposide treatment in secondary hemophagocytic syndrome: impact on healthcare-associated infections and survival
Authors: Dupont Thibault , Darmon Michael , Mariotte Eric , Lemiale Virginie , Fadlallah Jehane , Mirouse Adrien , Zafrani Lara , Azoulay Elie , Valade Sandrine
Published: October 2022

Background

Etoposide remains the cornerstone of symptomatic management of critically ill patients with secondary hemophagocytic syndrome (sHS). Risk of healthcare-associated infections (HAIs) in this setting with etoposide has never been assessed. We sought to evaluate the association between etoposide administration, HAIs occurrence and survival in critically ill adult patients with sHS. In this retrospective single-center study conducted in a university hospital ICU between January 2007 and March 2020, all consecutive patients with sHS were included. HAIs were defined as any microbiologically documented infection throughout ICU stay. Competing risk survival analysis was performed to determine factors associated with HAIs. Propensity score-based overlap weighting was performed to adjust for factors associated with etoposide use.

Results

168 patients with a median age of 49 [38, 59] were included. Forty-three (25.6%) patients presented with at least 1 microbiologically documented HAI throughout ICU stay. After adjustment, cumulative incidence of HAI was higher in patients receiving etoposide (p = 0.007), while survival was unaffected by etoposide status (p = 0.824). By multivariable analysis, etoposide treatment was associated with a higher incidence of HAIs (sHR 3.75 [1.05, 6.67]), whereas no association with survival (sHR 0.53 [0.20, 1.98]) was found. Other factors associated with increased mortality after adjustment included age, immunodepression, male sex, SOFA score > 13, and occurrence of HAI.

Conclusions

In patients with sHS, etoposide treatment is independently associated with increased occurrence of HAIs, whereas no association with survival was found. Intensivists should be aware of increased infectious risk, to promptly detect and treat infections in this specific setting. Studies to assess benefits from prophylactic anti-infectious agents in this setting are warranted and the lack of benefit of etoposide on survival needs to be interpreted cautiously.
Distributed reinforcement learning-based memory allocation for edge-PLCs in industrial IoT
Authors: Fu Tingting , Peng Yanjun , Liu Peng , Lao Haksrun , Wan Shaohua
Published: October 2022

The exponential device growth in industrial Internet of things (IIoT) has a noticeable impact on the volume of data generated. Edge-cloud computing cooperation has been introduced to the IIoT to lessen the computational load on cloud servers and shorten the processing time for data. General programmable logic controllers (PLCs), which have been playing important roles in industrial control systems, start to gain the ability to process a large amount of industrial data and share the workload of cloud servers. This transforms them into edge-PLCs. However, the continuous influx of multiple types of concurrent production data streams against the limited capacity of built-in memory in PLCs brings a huge challenge. Therefore, the ability to reasonably allocate memory resources in edge-PLCs to ensure data utilization and real-time processing has become one of the core means of improving the efficiency of industrial processes. In this paper, to tackle dynamic changes in arrival data rate over time at each edge-PLC, we propose to optimize memory allocation with Q-learning distributedly. The simulation experiments verify that the method can effectively reduce the data loss probability while improving the system performance.
LPCAT1 acts as an independent prognostic biomarker correlated with immune infiltration in hepatocellular carcinoma
Authors: Li Lan , Wang Xiao , Ding Yanni , Hui Nini , Su Bingjie , Yang Min
Published: October 2022

Background

Lysophosphatidylcholine acyltransferase 1 (LPCAT1) is overexpressed in multiple human tumors. However, the role of LPCAT1 in hepatocellular carcinoma (HCC) has not been understood. We aim to explore the relationships between LPCAT1 expression and prognosis, clinicopathological features, tumor microenvironment (TME), immune cell infiltration, immune checkpoint gene expression, and related signaling pathways in HCC. Furthermore, we also explored the relationship between LPCAT1 expression and drug sensitivity to HCC treatment.

Methods

The expression profiles were acquired from the Cancer Genome Atlas (TCGA) and the Human Protein Atlas (THPA). Immune status and infiltration in cancer tissues were explored using the single sample gene set enrichment analysis (ssGSEA) and CIBERSORT algorithm.

Results

LPCAT1 was overexpressed in HCC, and its expression was related to poor prognosis, LPCAT1 was an independent prognostic biomarker in HCC. Expression of LPCAT1 increased statistically with the increase of clinical stage and grade of HCC patients. GO and KEGG network analysis revealed that LPCAT1 positively associated molecules were mostly enriched in functions related to cell adhesion. The TME score of high-LPCAT1 group was significantly higher than that of low-LPCAT1 group. Immune infiltrating cells positively correlated with LPCAT1 expression were Macrophages M0, B cells memory, Dendritic cells activated, T cells regulatory and T cells gamma delta in HCC. We found a positive correlation between LPCAT1 and most immune checkpoint gene expression. The IC50 of 5-Fluorouracil, Gemcitabine, Mitomycin C, Sorafenib and Cabozantinib in patients with high-LPCAT1 expression was lower than that in patients with low-LPCAT1 expression. Our findings provide a wealth of information for further understanding of the biological functions and signaling pathways of LPCAT1 in HCC.

Conclusions

LPCAT1 is an independent prognostic biomarker and associated with tumor microenvironment, immune cell infiltration, immune checkpoint expression and drug sensitivity in hepatocellular carcinoma.