bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of therapeutic targets and prognostic biomarkers of CXC chemokines in cervical cancer microenvironment
Authors: Kong Weina , Zhao Gang , Chen Haixia , Wang Weina , Shang Xiaoqian , Sun Qiannan , Guo Fan , Ma Xiumin 
Published: July 2021

Abstract
Background
The tumor microenvironment (TME) has received an increasing amount of attention. CXC chemokines can regulate immune cell transport and tumor cell activity to exert anti-tumor immunity. However, studies on the expression and prognosis of CXC chemokines in cervical cancer (CC) are more limited.

Methods
The study investigated the role of CXC chemokines in TME of CC by using public databases. Moreover, quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) of CXC chemokines were performed to further verify.

Results
The transcriptional levels of CXCL1/3/5/6/8/9/10/11/13/16/17 in CC tissues were significantly elevated while the transcriptional levels of CXCL12/14 were significantly reduced. We reached a consistent conclusion that the expression of CXCL9/10/11/13 was verified by quantitative real-time PCR and immunohistochemistry. Moreover, CC patients with low transcriptional levels of CXCL1/2/3/4/5/8 were significantly associated with longer overall survival (OS). The CCL family was related to CXC chemokines neighboring alteration. RELA, NFKB1, LCK and PAK2 were the key transcription factors and kinase targets of CXC chemokines, respectively. We also found there were significant correlations between the expression of CXCL9/10/11 and the infiltration of immune cells (CD8+ T cell, CD4+ T cell, neutrophils and dendritic cells).

Conclusions
In brief, we conducted a comprehensive analysis of CXC chemokines via clinical data and some online public databases. Our results may provide a new idea for the selection of immunotherapeutic targets and prognostic biomarkers for cervical cancer.
Midazolam increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via the miR-194-5p/HOOK3 axis
Authors: Sun Tingting , Chen Jing , Sun Xuechao , Wang Guonian 
Published: July 2021

Abstract
Backgrounds
As previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms.

Methods
We performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues.

Results
The cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 μg/ml) and low-dose midazolam (10 μg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3’ untranslated region (3’UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells.

Conclusions
Taken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.
Factors affecting job choice among physician anesthesia providers in Uganda: a survey of income composition, discrete choice experiment, and implications for the decision to work rurally
Authors: Law Tyler J. , Subhedar Shivani , Bulamba Fred , O’Hara Nathan N. , Nabukenya Mary T. , Sendagire Cornelius , Hewitt-Smith Adam , Lipnick Michael S. , Tumukunde Janat 
Published: July 2021

Abstract
Background
One of the biggest barriers to accessing safe surgical and anesthetic care is lack of trained providers. Uganda has one of the largest deficits in anesthesia providers in the world, and though they are increasing in number, they remain concentrated in the capital city. Salary is an oft-cited barrier to rural job choice, yet the size and sources of anesthesia provider incomes are unclear, and so the potential income loss from taking a rural job is unknown. Additionally, while salary augmentation is a common policy proposal to increase rural job uptake, the relative importance of non-monetary job factors in job choice is also unknown.

Methods
A survey on income sources and magnitude, and a Discrete Choice Experiment examining the relative importance of monetary and non-monetary factors in job choice, was administered to 37 and 47 physician anesthesiologists in Uganda, between May–June 2019.

Results
No providers worked only at government jobs. Providers earned most of their total income from a non-government job (50% of income, 23% of working hours), but worked more hours at their government job (36% of income, and 44% of working hours). Providers felt the most important job attributes were the quality of the facility and scope of practice they could provide, and the presence of a colleague (33% and 32% overall relative importance). These were more important than salary and living conditions (14% and 12% importance).

Conclusions
No providers accepted the salary from a government job alone, which was always augmented by other work. However, few providers worked only nongovernment jobs. Non-monetary incentives are powerful influencers of job preference, and may be leveraged as policy options to attract providers. Salary continues to be an important driver of job choice, and jobs with fewer income generating opportunities (e.g. private work in rural areas) are likely to need salary augmentation to attract providers.
Hhex inhibits cell migration via regulating RHOA/CDC42-CFL1 axis in human lung cancer cells
Authors: Li Xiaopeng , Ma Guilin , Guo Wenjie , Mu Ning , Wang Yingying , Liu Xiangguo , Su Ling 
Published: July 2021

Abstract
Background
Hhex(human hematopoietically expressed homeobox), also known as PRH, is originally considered as a transcription factor to regulate gene expression due to its homebox domain. Increasing studies show that Hhex plays a significant role in development, including anterior–posterior axis formation, vascular development and HSCs self-renewal etc. Hhex is linked to many diseases such as cancers, leukemia, and type-2 diabetes. Although Hhex is reported to inhibit cell migration and invasion of breast and prostate epithelial cells by upregulating Endoglin expression, the effect and molecular mechanism for lung cancer cell motility regulation remains elusive.

Methods
Human non-small cell lung cancer cells and HEK293FT cells were used to investigate the molecular mechanism of Hhex regulating lung cancer cell migration by using Western blot, immunoprecipitation, wound-healing scratch assay, laser confocal.

Results
Our data indicated that Hhex could inhibit cell migration and cell protrusion formation in lung cancer cells. In addition, Hhex inhibited CFL1 phosphorylation to keep its F-actin-severing activity. RHOGDIA was involved in Hhex-induced CFL1 phosphorylation regulation. Hhex enhanced RHOGDIA interaction with RHOA/CDC42, thus maintaining RHOA/CDC42 at an inactive form.

Conclusion
Collectively, these data indicate that Hhex inhibited the activation of RHOA/CDC42 by enhancing interaction of RHOGDIA with RHOA/CDC42, and then RHOA/ CDC42-p-CFL1 signaling pathway was blocked. Consequently, the formation of Filopodium and Lamellipodium on the cell surface was suppressed, and thus the ability of lung cancer cells to migrate was decreased accordingly. Our findings show Hhex plays an important role in regulating migration of lung cancer cells and may provide a potential target for lung cancer therapy.
Technology-supported sitting balance therapy versus usual care in the chronic stage after stroke: a pilot randomized controlled trial
Authors: Thijs Liselot , Voets Eline , Wiskerke Evelien , Nauwelaerts Thomas , Arys Yves , Haspeslagh Harold , Kool Jan , Bischof Patrick , Bauer Christoph , Lemmens Robin , Baumgartner Daniel , Verheyden Geert 
Published: July 2021

AbstractBackgroundTechnology development for sitting balance therapy and trunk rehabilitation is scarce. Hence, intensive one-to-one therapist-patient training is still required. We have developed a novel rehabilitation prototype, specifically aimed at providing sitting balance therapy. We investigated whether technology-supported sitting balance training was feasible and safe in chronic stroke patients and we determined whether clinical outcomes improved after a four-week programme, compared with usual care.MethodsIn this parallel-group, assessor-blinded, randomized controlled pilot trial, we divided first-event chronic stroke participants into two groups. The experimental group received usual care plus additional therapy supported by rehabilitation technology, consisting of 12 sessions of 50 min of therapy over four weeks. The control group received usual care only. We assessed all participants twice pre-intervention and once post-intervention. Feasibility and safety were descriptively analysed. Between-group analysis evaluated the pre-to-post differences in changes in motor and functional outcomes.ResultsIn total, 30 participants were recruited and 29 completed the trial (experimental group: n = 14; control group: n = 15). There were no between-group differences at baseline. Therapy was evaluated as feasible by participants and therapist. There were no serious adverse events during sitting balance therapy. Changes in clinical outcomes from pre- to post-intervention demonstrated increases in the experimental than in the control group for: sitting balance and trunk function, evaluated by the Trunk Impairment Scale (mean points score (SD) 7.07 (1.69) versus 0.33 (2.35);p < 0.000); maximum gait speed, assessed with the 10 Metre Walk Test (mean gait speed 0.16 (0.16) m/s versus 0.06 (0.06) m/s;p = 0.003); and functional balance, measured using the Berg balance scale (median points score (IQR) 4.5 (5) versus 0 (4);p = 0.014).ConclusionsTechnology-supported sitting balance training in persons with chronic stroke is feasible and safe. A four-week, 12-session programme on top of usual care suggests beneficial effects for trunk function, maximum gait speed and functional balance.Trial Registration:ClinicalTrials.gov identifier: NCT04467554,https://clinicaltrials.gov/ct2/show/NCT04467554, date of Registration: 13 July 2020.
Geriatric depression and quality of life in North Shoa Zone, Oromia region: a community cross-sectional study
Authors: Jemal Kemal , Hailu Dejene , Tesfa Bikila , Lama Tasfaye , Kinati Tadele , Mengistu Endeshaw 
Published: July 2021

AbstractIntroductionDepression and low quality of life are severe conditions that lead to disability and mortality, common in high and low-resourced countries. Therefore, this study aimed to assess geriatric depression, quality of life, and associated factors among elderly persons in the low-resource country.MethodsA community-based cross-sectional study was used from March to April 2020. The depression and quality of life were assessed using the standardized and pre-tested geriatric depression scale (GDS) and the World Health Organization Quality Of Life (WHOQOL)-BREF, respectively. A multi-stage sampling technique was employed to select woreda and study participants. For data input and analysis, Epi-data version 4.3 and SPSS version 23 were utilized, consecutively. Bivariable and multivariable in the logistic regression analysis were done, and significance was determined at the odds ratio with a 95% confidence interval andPvalue < 0.05.ResultsA total of 822 elderly persons participated in face to face interviewed-administered questionnaire. More than half 54.5% (n = 448) of elderly persons had depression and 51.8% (n = 426) of elderly participants had low quality of life. Advanced age, single participants, not having a formal education, living alone, and having chronic diseases were significantly associated with both the depression symptoms and low overall WHOQOL-BREF. Depression was correlated with low quality of life.ConclusionWe found that elderly persons have a high risk of depression symptoms and a low quality of life. The Ethiopian Ministry of Health should develop psychological interventions, providing ongoing education for the elderly, and monitoring the health of the elderly population to address the specific needs of elderly persons who have been impacted by the aging process.
Ethnobotany of the Aegadian Islands: safeguarding biocultural refugia in the Mediterranean
Authors: La Rosa Alfonso , Cornara Laura , Saitta Alessandro , Salam Akram M. , Grammatico Santo , Caputo Marco , La Mantia Tommaso , Quave Cassandra L. 
Published: July 2021

Abstract
Background
The Aegadian Islands are located west of Trapani, Sicily. Once the site of bountiful tuna fisheries and fruit orchards (plums, peaches, apricots), grapevines, prickly pears, and grains, the local economy is now based on tourism, and many traditional agricultural and maritime practices have been abandoned. In this study, we aimed to evaluate the state of traditional ecological knowledge (TEK) concerning the use of wild and cultivated plants and fungi for human health, food, maritime, and agricultural purposes on the islands of Levanzo, Favignana, and Marettimo and compare present-day practices with those documented in the past.

Methods
In-depth semi-structured interviews were conducted in Italian with 48 participants with prior informed consent from May 2016 to July 2017 and October 2018. Herbarium voucher specimens of wild species were collected for herbarium deposit. A rigorous literature review of scientific and other local reports on TEK of wild flora and their application in food, health, and household applications was undertaken for the purpose of comparing findings from this field study with prior reports.

Results
A total of 122 plant and five fungal taxa representing 54 families were cited for 355 uses. Among the most pervasive species in the landscape, Agave americana and A. sisalana had diverse applications in the past, which ranged from cordage for agricultural and maritime applications to tools for sewing, eating land snails, and constructing furniture. Fields of Ferula communis also dominate the landscape, and the dry stems were used extensively in furniture making; this species also serves as an environmental indicator for the location of the most preferred edible mushrooms, Pleurotus eryngii var. ferulae. Other important flora included topical medicinal applications of Glaucium flavum for hematomas and Artemisia arborescens for ritual bathing of newborns.

Conclusion
While many plant-based traditions have disappeared from daily practice, especially those related to traditional fishing and health practices, they remain in the memories of the eldest subset of the population. Documenting this knowledge before it disappears from oral history is a key factor in reducing loss of TEK and biocultural diversity, safeguarding the role of the Aegadian Islands as biocultural refugia.
Functional and mutational analysis after radiation and cetuximab treatment on prostate carcinoma cell line DU145
Authors: Schneider Raik , Gademann Günther , Ochel Hans-Joachim , Neumann Karsten , Jandrig Burkhard , Hass Peter , Walke Mathias , Schostak Martin , Brunner Thomas , Christoph Frank 
Published: July 2021

Abstract
Background
Epidermal Growth Factor Receptor is often overexpressed in advanced prostate carcinoma. In-vitro-studies in prostate carcinoma cell line DU145 have demonstrated increased sensibility to radiation after cetuximab treatment, but clinical data are not sufficient to date.

Methods
We analyzed effects of radiation and cetuximab in DU145 and A431 using proliferation, colony-forming-unit- and annexin-V-apoptosis-assays. Changes in protein expression of pEGFR and pERK1/2 after radiation and cetuximab treatment were analyzed. Using NGS we also investigated the impact of cetuximab long-term treatment.

Results
Cell counts in DU145 were reduced by 44% after 4 Gy (p = 0.006) and 55% after 4 Gy and cetuximab (p < 0.001). The surviving fraction (SF) was 0.69 after 2 Gy, 0.41 after 4 Gy and 0.15 after 6 Gy (each p < 0.001). Cetuximab treatment did not alter significantly growth reduction in 4 Gy radiated DU145 cells, p > 0.05 or SF, p > 0.05, but minor effects on apoptotic cell fraction in DU145 were detected. Using western blot, there were no detectable pEGFR and pERK1/2 protein signals after cetuximab treatment. No RAS mutation or HER2 amplification was detected, however a TP53 gen-mutation c.820G > T was found.

Conclusions
Radiation inhibits cell-proliferation and colony-growth and induces apoptosis in DU145. Despite blocking MAP-Kinase-pathway using cetuximab, no significant radiation-sensitizing-effect was detected. Cetuximab treatment did not induce resistance-mutations. Further research must clarify which combination of anti-EGFR treatment strategies can increase radiation-sensitizing-effects.
Interfractional target changes in brain metastases during 13-fraction stereotactic radiotherapy
Authors: Uto Megumi , Ogura Kengo , Katagiri Tomohiro , Takehana Keiichi , Mizowaki Takashi 
Published: July 2021

Abstract
Background
The risk for radiation necrosis is lower in fractionated stereotactic radiotherapy (SRT) than in conventional radiotherapy, and 13-fraction SRT is our method of choice for the treatment of brain metastases ≥ around 2 cm or patients who are expected to have a good prognosis. As 13-fraction SRT lasts for at least 17 days, adaptive radiotherapy based on contrast-enhanced mid-treatment magnetic resonance imaging (MRI) is often necessary for patients undergoing 13-fraction SRT. In this study, we retrospectively analyzed interfractional target changes in patients with brain metastases treated with 13-fraction SRT.

Methods
Our analyses included data from 23 patients and 27 metastatic brain lesions treated with 13-fraction SRT with dynamic conformal arc therapy. The peripheral dose prescribed to the planning target volume (PTV) was 39–44.2 Gy in 13-fractions. The gross tumor volume (GTV) of the initial SRT plan (initial GTV), initial PTV, and modified GTV based on the mid-treatment MRI scan (mid-treatment GTV) were assessed.

Results
The median initial GTV was 3.8 cm3 and the median time from SRT initiation to the mid-treatment MRI scan was 6 days. Compared to the initial GTV, the mid-treatment GTV increased by more than 20% in five lesions and decreased by more than 20% in five lesions. Interfractional GTV volume changes of more than 20% were not significantly associated with primary disease or the presence of cystic components/necrosis. The mid-treatment GTV did not overlap perfectly with the initial PTV in more than half of the lesions.

Conclusions
Compared to the initial GTV, the mid-treatment GTV changed by more than 20% in almost one-third of lesions treated with 13-fraction SRT. As SRT usually generates a steep dose gradient as well as increasing the maximum dose of PTV compared to conventional radiotherapy, assessment of the volume and locational target changes and adaptive radiotherapy should be considered as the number of fractions increases.
Implementation of Enhanced Recovery After Surgery (ERAS) protocol for elderly patients receiving surgery for intertrochanteric fracture: a propensity score-matched analysis
Authors: Zhu Wenhao , Yan Yinjie , Sun Yijin , Fan Zhaoxiang , Fang Niangkang , Zhang Yunlu , Yin Mengchen , Wan Hongbo , Mo Wen , Lu Wei , Wu Xuequn 
Published: July 2021

Abstract
Purpose
Enhanced Recovery After Surgery (ERAS) is a multimodal approach to perioperative care that aims to reduce patient perioperative complications, accelerate patient recovery, and improve patient satisfaction by refining and optimizing all perioperative management processes. By comparing two groups of patients before and after the implementation of ERAS for intertrochanteric fracture (ITF) with a matching analysis of propensity score (PS), we aimed to demonstrate that the implementation of ERAS protocol shortens the length of hospital stay (LOS), reduces pain, decreases the incidence of postoperative complications, and promotes functional recovery of the joint.

Methods
We selected 2 periods of 1 year, before (n=98patients) and after ERAS implementation (n=92patients). Data were collected on patient demographics, operative and perioperative details, LOS, VAS score, Harris score, and 30-day complications. ERAS-trained nurses are engaged to support patients at each step of the pre/per/postoperative process, including completing a satisfaction survey, with the help of a mobile app. PS analyses were used for dealing with confounding bias in this retrospective observational study.

Results
After PS matching, the outcomes of 124 well-balanced pairs of patients were compared (conventional vs ERAS). LOS was significantly reduced from 24.3±3.9 to 15.2±2.9 days (P<0.001). With the same preoperative VAS scores, we found that patients in the ERAS group had significantly lower postoperative VAS scores than those in the conventional group at days 3 and 7 (P<0.001), but the difference was not statistically significant at day 14. patients in the ERAS group had higher Harris scores than those in the conventional group at 1 and 3 months, but the difference was not significant at 6 months. In addition, we found that only one patient in the ERAS group developed complications, while nine patients in the conventional group developed different complications. There was no significant difference concerning the satisfaction survey.

Conclusion
The introduction of ERAS for ITF in our institution has resulted in a significant decrease in LOS, alleviated patient pain, promoted early recovery of patient’s hip function while effectively preventing complications, and obtained patient satisfaction.