bluuebunny/crossref_metadata_2025_split huggingface dataset:
C9orf16 represents the aberrant genetic programs and drives the progression of PDAC
Authors: Chen Xiaojun , Zhang Hong , Xiao Bo 
Published: October 2022

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.