bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circ_0000471 suppresses the progression of ovarian cancer through mediating mir‐135b‐5p/dusp5 axis
Authors: Yu Shanshan , Yu Maowen , Chen Jianjun , Tang Hongbo , Gong Wuqing , Tan Hui 
Published: November 2022

AbstractBackgroundOvarian cancer (OC) is a common gynecologic cancer with high incidence and mortality. We attempted to investigate the role of circular RNA_0000471 (circ_0000471) in OC progression and its associated mechanism.MethodsReverse transcription‐quantitative polymerase chain reaction (RT‐qPCR) and western blot assay were conducted to measure RNA and protein expression, respectively. Cell proliferation was analyzed by Cell Counting Kit‐8 (CCK8) assay, colony formation assay, and 5‐Ethynyl‐2′‐deoxyuridine (EdU) assay. Cell apoptosis was assessed by flow cytometry. Cell migration and invasion were analyzed by wound healing assay and transwell assay, respectively. Dual‐luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to verify the target relationships. Xenograft tumor model was established to assess the role of circ_0000471 on tumor growth in vivo.ResultsCirc_0000471 expression was down‐regulated in OC tissues and cell lines. Circ_0000471 overexpression blocked the proliferation, migration, and invasion and triggered the apoptosis of OC cells. Circ_0000471 served as a molecular sponge for microRNA‐135b‐5p (miR‐135b‐5p), and circ_0000471 overexpression‐mediated anti‐tumor influences in OC cells were largely reversed by the overexpression of miR‐135b‐5p. Dual specificity phosphatase 5 (DUSP5) was a target of miR‐135b‐5p, and miR‐135b‐5p silencing‐induced anti‐tumor effects were largely counteracted by the interference of DUSP5. Circ_0000471 increased DUSP5 expression by sponging miR‐135b‐5p in OC cells. Circ_0000471 overexpression restrained the growth of xenograft tumors in vivo.ConclusionOverexpression of circ_0000471 inhibited OC development by targeting miR‐135b‐5p/DUSP5 axis, indicating that circ_0000471 may be a new potential target for OC treatment.
Identifying best‐practice features of diabetic retinopathy treatment models for Aboriginal and Torres Strait Islander Australians
Authors: Gilden Rosamond , McKenzie Rosemary , Anjou Mitchell D. 
Published: November 2022

AbstractObjectiveIndigenous Australians are nearly three times more likely to have diabetes than non‐Indigenous Australians. The prevalence of diabetes‐related vision impairment for Indigenous Australians is 5.5% compared to 1.5% for non‐Indigenous Australians, and treatment rates are lower for Indigenous Australians. Despite this situation, there is limited evidence on effective service delivery models for diabetic retinopathy care and treatment. This study seeks to identify best‐practice features of diabetic retinopathy care that could be used to inform current and future service delivery models for Indigenous Australians with diabetic retinopathy.SettingAll states, territories and geographic remoteness categories in Australia.ParticipantsEight ophthalmologists engaged in providing eye healthcare to Indigenous Australians.DesignSemi‐structured interviews were conducted. The Framework Approach was used to conduct a thematic analysis of the interviews to facilitate identification of key themes and issues that emerged from these discussions.ResultsSeven best‐practice features for service delivery of diabetic retinopathy treatment for Indigenous Australians were identified. These were: cultural safety, affordability and accessibility, partnerships with key stakeholders, timeliness, integration with primary care, clarity of guidelines, and clinician attitude and motivation.ConclusionThe findings from this study identified seven best‐practice features for diabetic retinopathy treatment. These have the potential to inform and influence how care is delivered to Indigenous Australians. Although further research is warranted to capture other service provider inputs and Indigenous end‐user perspectives, these features in the meantime can begin to inform the decisions of the Indigenous eyecare sector on policy reforms and best‐practice diabetic retinopathy treatment approaches.
Prognostic significance of age on superficial spreading melanoma after resection: lessons from SEER database involving 12 536 patients
Authors: Sun Jie , Zhou Jie‐Song , Wang Yu‐Chong , Dai Hai‐Ying , Sun Meng‐Yan , Lv Chuan 
Published: November 2022

AbstractBackgroundThis study sought to analyse the impact of elderly age on long‐term prognosis of superficial spreading melanoma (SSM) after surgery.MethodsA population‐based cohort of patients undergoing resection for SSM from 2004 to 2015 was collected, using data from National Cancer Institute‘ Surveillance, Epidemiology, and End Results (SEER)* Stat software. Patients were divided into the non‐elderly group (≤70 years) and elderly group (>70 years). Baseline characteristics and long‐term survivals were compared between the two groups. A 1:1 propensity score matching (PSM) was used to reduce the risk of bias. The impact of the elderly age on overall survival (OS) and cause‐specific mortality (CSM) was estimated by Cox‐regression and competing‐risk regression models.ResultsAmong 12 536 patients with SSM after resection included into the cohort, 8664 patients were ≤70 years, and 3872 were >70 years. Patients in the elderly group had higher incidences of multiple tumours, worse tumour stage and infiltration degree, lymphatic metastasis, and larger size of primary lesions. Using PSM, 3581 pairs of patients were created. On matched analysis, the elderly group was associated with worse OS and CSM. On multivariable Cox‐regression and competing‐risk regression analyses, elderly age was identified as an independent risk factor of OS and CSM after adjusting for other prognostic variables.ConclusionsThe elderly age of patients was independently associated with worse OS and CSM after resection of SSM when baseline and tumour characteristics were balanced. Adjuvant therapy and individualized strategy on follow‐up should be made for elderly patients after resection of SSM.
Surgical management of injured ADF personnel deployed to Afghanistan 2001–2021
Authors: Pilgrim Charles H. C. , Brennan Leonard 
Published: November 2022

AbstractIntroductionA comprehensive review of the surgical management of injuries sustained by deployed members of the Australian Defence Force (ADF) during Operation SLIPPER and HIGHROAD in Afghanistan has not previously been undertaken. Understanding the mechanism of injury, injury types sustained and surgical intervention undertaken should provide valuable information for future health planning and surgical capability determination.MethodsRetrospective chart review of scanned medical records of injured personnel identified through casualty register examination was undertaken.ResultsThere were 259 ADF personnel injured in Afghanistan between January 2002 and December 2021, of which 53 were seriously (SI), or very seriously injured (VSI). Case notes for 90 of 101 casualties including those sustaining VSI, SI and those classified as being in satisfactory condition, but likely requiring surgery and/or returned to Australia following trauma, were available for review. Most patients with VSI/SI required surgery (93%) and most were returned to Australia following injury (91%). Almost two‐thirds (64.4%) of initial surgery was undertaken at a Role 2 E medical treatment facility (MTF). Gun‐shot wound (GSW) was the commonest injuring mechanism (47%) followed by blast injury (39.6%). Orthopaedic (32.2%) and soft tissue initial wound surgery (47.1%) were the commonest surgical procedures.DiscussionSurgical management of military trauma was undertaken at multiple sites by multiple surgical teams from different nationalities delivering exceptional results and conforming to modern principles of damage control surgery. The military trauma system is distinctly different from its civilian counterpart with dispersion of assets requiring multiple episodes of casualty movement between echelons of care rather than centralization at level 1 trauma centres. Despite this, excellent results are achievable. Strengthening lines of communication and documentation would reinforce the ability of the military trauma system to continue to provide such results, and regular oversight and review of surgical caseload would align military trauma surgery with civilian standards. The benchmark set by the United States Department of Defense Trauma Registry should be replicated for Australian led combat operations and modified to facilitate interoperability to support future coalition combat operations.
Evaluation of treosulfan cumulative exposure in paediatric patients through population pharmacokinetics and dosing simulations
Authors: Rosser Sebastian P. A. , Lee Samiuela , Kohli Shruti , Keogh Steven J. , Chung Jason , O'Brien Tracey , Fraser Christopher , McLachlan Andrew J. , Shaw Peter J. , Nath Christa E. 
Published: November 2022

AimTo investigate the pharmacokinetics (PK) of intravenous treosulfan in paediatric patients undergoing haematopoietic stem cell transplantation (HSCT) for a broad range of diseases and to explore the impact of different dosing regimens on treosulfan exposure (area under the concentration–time curve, AUC0→∞) through dosing simulations.MethodsA prospective multicentre PK study was conducted using treosulfan concentration data (n = 423) collected from 53 children (median age 3.5, range 0.2–17.0 years) receiving three daily age‐guided doses (10–14 g/m2). Population PK modelling was performed using NONMEM software, utilising a stepwise forward selection backward elimination method and likelihood‐ratio test for screening covariates to describe PK variability. Monte Carlo simulation was used to generate patient PK data for 10 000 virtual paediatric patients and cumulative AUC0→∞ values were evaluated using age, body surface area (BSA) and model‐based dosing regimens, targeting 4800 mg*h/L.ResultsTreosulfan concentration data were described using a one‐compartment PK model with first‐order elimination. Population mean (95% CI) estimates for clearance (CL) and volume of distribution (V) were 16.3 (14.9–18.1) L/h and 41.9 (38.8–45.1) L, respectively. Allometrically scaled body weight was the best covariate descriptor for CL and V, and maturational age further explained variability in CL. Dosing simulations indicated that in young patient groups (<2 years), a model‐based dosing regimen more accurately achieved the target AUC0→∞ (58.3%) over the age (42.6%) and BSA‐based (51.3%) regimens.ConclusionTreosulfan disposition was described through allometric body weight and maturational age descriptors. Model‐informed dosing is recommended for patients under 2 years. Treosulfan PK parameters and AUC0→∞ were not influenced by patient disease.
Artesunate, a new antimalarial clinical drug, exhibits potent anti‐AML activity by targeting the ROS/Bim and TFRC/Fe2+ pathways
Authors: Liu Yi , Li Han , Luo Zhihong , Yu You , Yang Jingzhao , Zhang Min , Law Betty Yuen Kwan , Huang Zan , Li Wenhua 
Published: November 2022

Background and PurposeArtesunate, approved by the Food and Drug Administration in 2020 as a new treatment for severe malaria, also shows anti‐tumour activity against acute myeloid leukaemia (AML). However, the underlying molecular mechanism(s) of artesunate‐induced apoptosis and differentiation of AML is not clearly elucidated.Experimental ApproachThe biological effects of artesunate on AML were explored in vitro, using cells from AML patients and leukaemia cell lines, and in vivo, using female C57BL/6 or nude nu/nu BALB/c mice. Underlying mechanisms in vitro were examined with the Trypan blue dye exclusion assay, western blotting and flow cytometry. Effects of artesunate in C57BL/6 mice intravenously injected with murine AML cells (C1498‐GFP) were assessed by numbers of AML cells and by survival.Key ResultsIn vitro, artesunate promoted apoptosis and differentiation in both leukaemia cell lines and patient‐derived primary leukaemia cells. Mechanistically, artesunate promoted cell apoptosis by triggering reactive oxygen species (ROS) production and increasing expression of the pro‐apoptotic protein Bim. Interestingly, transferrin receptor 1 (TFRC)‐mediated regulation of intracellular iron homeostasis also played an essential role in AML cell differentiation induced by artesunate. In vivo, artesunate slowed AML progression and prolonged survival in a mouse leukaemia model. Notably, artesunate displayed no apparent toxicity towards healthy haematopoietic stem cells, bone marrow mononuclear cells or experimental animals.Conclusion and ImplicationsArtesunate is a safe agent with significant anti‐leukaemia effects in mice and may serve as a promising chemotherapeutic strategy for patients with AML, based on two different mechanisms, targeting the ROS/Bim and the TFRC/Fe2+ pathways.
Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma
Authors: Zhou Li , Mao Lin‐Hong , Li Xia , Wang Qing‐Liang , Chen Si‐Yuan , Chen Zhi‐Ji , Lei Jing , Liu Hong‐Tao , Liao Si‐Qi , Ran Tao , Li Xiao‐Qin , Zhou Zhi‐Hang , He Song 
Published: November 2022

AbstractSorafenib is one a first‐line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib‐resistant SMMC‐7721 cells compared to parental cells. NFIB knockdown not only sensitized drug‐resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib‐induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.
Pembrolizumab in Asian patients with microsatellite‐instability‐high/mismatch‐repair‐deficient colorectal cancer
Authors: Yoshino Takayuki , Andre Thierry , Kim Tae Won , Yong Wei Peng , Shiu Kai‐Keen , Jensen Benny Vittrup , Jensen Lars Henrik , Punt Cornelis J. A. , Smith Denis , Garcia‐Carbonero Rocio , Alcaide‐Garcia Julia , Gibbs Peter , de la Fouchardiere Christelle , Rivera Fernando , Elez Elena , Le Dung T. , Adachi Noriaki , Fogelman David , Marinello Patricia , Diaz Luis A. 
Published: November 2022

AbstractThe phase 3 KEYNOTE‐177 study evaluated pembrolizumab versus chemotherapy with or without bevacizumab or cetuximab in patients with newly diagnosed, microsatellite‐instability‐high (MSI‐H)/mismatch‐repair‐deficient (dMMR) metastatic colorectal cancer (mCRC). Primary endpoints were progression‐free survival (PFS) per RECIST v1.1 by blinded independent central review (BICR) and overall survival (OS). Secondary endpoints were overall response rate (ORR) per RECIST v1.1 by BICR and safety. Here, we report results from the post hoc analysis of patients who were enrolled in Asia from the final analysis (FA) of KEYNOTE‐177. A total of 48 patients from Japan, Korea, Singapore, and Taiwan (pembrolizumab, n = 22; chemotherapy, n = 26) were included. At FA, median time from randomization to data cutoff (February 19, 2021) was 45.3 (range 38.1–57.8) months with pembrolizumab and 43.9 (range 36.6–55.1) months with chemotherapy. Median PFS was not reached (NR; 95% confidence interval [CI] 1.9 months–NR) with pembrolizumab versus 10.4 (95% CI 6.3–22.0) months with chemotherapy (hazard ratio [HR] 0.56, 95% CI 0.26–1.20). Median OS was NR (range 13.8 months–NR) versus 30.0 (14.7–NR) months (HR 0.65, 95% CI 0.27–1.55) and ORR was 50% (95% CI 28–72) versus 46% (95% CI 27–67). Grade 3/4 treatment‐related adverse events (TRAEs) were reported by two patients (9%) in the pembrolizumab arm and 20 (80%) in the chemotherapy arm. Immune‐mediated adverse events or infusion reactions were reported by six patients (27%) and 10 patients (40%), respectively. No deaths due to TRAEs occurred. These data support first‐line pembrolizumab as a standard of care for patients from Asia with MSI‐H/dMMR mCRC. ClinicalTrials.gov identifier: NCT02563002.
Selection bias due to delayed comprehensive genomic profiling in Japan
Authors: Tamura Taichi , Ikegami Masachika , Kanemasa Yusuke , Yomota Makiko , Furusawa Akiko , Otani Ryohei , Saita Chiaki , Yonese Ichiro , Onishi Tomoko , Kobayashi Hiroshi , Akiyama Toru , Shimoyama Tatsu , Aruga Tomoyuki , Yamaguchi Tatsuro 
Published: November 2022

AbstractPatients with advanced cancer undergo comprehensive genomic profiling in Japan only after treatment options have been exhausted. Patients with a very poor prognosis were not able to undergo profiling tests, resulting in a selection bias called length bias, which makes accurate survival analysis impossible. The actual impact of length bias on the overall survival of patients who have undergone profiling tests is unclear, yet appropriate methods for adjusting for length bias have not been developed. To assess the length bias in overall survival, we established a simulation‐based model for length bias adjustment. This study utilized clinicogenomic data of 8813 patients with advanced cancer who underwent profiling tests at hospitals throughout Japan between June 2019 and April 2022. Length bias was estimated by the conditional Kendall τ statistics and was significantly positive for 13 of the 15 cancer subtypes, suggesting a worse prognosis for patients who underwent profiling tests in early timing. The median overall survival time in colorectal, breast, and pancreatic cancer from the initial survival‐prolonging chemotherapy with adjustment for length bias was 937 (886–991), 1225 (1152–1368), and 585 (553–617) days, respectively (median; 95% credible interval). Adjusting for length bias made it possible to analyze the prognostic relevance of oncogenic mutations and treatments. In total, 12 tumor‐specific oncogenic mutations correlating with poor survival were detected after adjustment. There was no difference in survival between FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) or gemcitabine with nab‐paclitaxel‐treated groups as first‐line chemotherapy for pancreatic cancer. Adjusting for length bias is an essential part of utilizing real‐world clinicogenomic data.
“Trying to be positive in the face of the storm”: The experiences of independent college students during the COVID‐19 pandemic
Authors: Sapiro Beth , Shpiegel Svetlana , Ventola Marissa , Quiroz Silvia Ramirez , Nwankwo Oomi Helen , Munyereyi Tariro 
Published: November 2022

AbstractThe COVID‐19 pandemic created multiple stressors for college students, particularly for young adults experiencing multiple forms of disadvantage. Little is known about the pandemic experiences of independent college students, many of whom are emancipated minors, former wards of the state, and other students who lack familial financial and practical support as they pursue higher education. Twenty‐three independent students, ages 18–23, from one northeastern university were interviewed to understand how independent students were affected by the COVID‐19 pandemic, and their needs for support from the university during this time. Most participants were identified as Black or Latinx, and two thirds were first‐generation college students. Participants reported an overall lack of support from their families prior to the pandemic. During the pandemic, they experienced compounding academic, economic, and mental health‐related stressors. Students responded to these stressors in resilient and resourceful ways, by adapting to their new realities, expressing gratitude, and finding opportunities for self‐growth. Participants recommend that institutions of higher education support independent students during periods of emergency through providing financial assistance, offering opportunities for connection with both adults and peers, and demonstrating administrative flexibility and understanding of their unique needs.
Drilling‐ and withdrawing‐related thermal effects of implant site preparation for ceramic and stainless steel twist drills in standardized bovine bone
Authors: Tur Dino , Giannis Katharina , Unger Ewald , Mittlböck Martina , Rausch‐Fan Xiaohui , Strbac Georg D. 
Published: November 2022

AbstractIntroductionExcessive surgical trauma is believed to be among the most important causes for early implant losses. As thermal injury to the bone is not only dependent on the amount of generated heat but also on the tissue exposure time, and the greatest temperature increase was found within the withdrawing period, the entire osteotomy procedure with the parameters contributing to thermal damage is of particular clinical relevance. The aim of this study was to investigate the thermal performance of metal‐based and ceramic implant drills regarding the temperature exposure time during the whole osteotomy process.Materials and MethodsThis investigation consisted of 240 individual preparations in total, comprising two different drilling depths (10 and 16 mm), two irrigation methods (external and without irrigation), two implant drill materials (stainless steel and zirconia), and three consecutive drill diameters per material (2.0/2.2, 2.8, and 3.5 mm) with 10 identical repetitions. Real‐time multichannel temperature measurement was conducted during automated drilling procedures in standardized bovine bone specimens.ResultsThe maximum temperature changes were highly associated with the time period of passive drill withdrawing (p ≤ 0.05), irrespective of drill material, drilling depth, or drill diameter. Statistically significant differences in temperature generation between stainless steel and ceramic drills were observed in irrigated testing sites at both drilling depths with smaller drill diameters (2.0/2.2 and 2.8 mm, p ≤ 0.05).ConclusionResults of this in vitro study could demonstrate a strong association between the highest temperature increase and the passive withdrawing time period in both investigated drill materials. Considering these findings and the resulting thermal bone damage due to the whole surgical procedure, high overall temperatures in combination with a prolonged heat exposure time may impact the future osseointegration process.