bluuebunny/crossref_metadata_2025_split huggingface dataset:
DNMT3A R882H mutation drives daunorubicin resistance in acute myeloid leukemia via regulating NRF2/NQO1 pathway
Authors: Chu Xuan , Zhong Liang , Dan Wenran , Wang Xiao , Zhang Zhonghui , Liu Zhenyan , Lu Yang , Shao Xin , Zhou Ziwei , Chen Shuyu , Liu Beizhong 
Published: October 2022

Abstract
Background
DNA methyltransferase 3A (DNMT3A) often mutate on arginine 882 (DNMT3AR882) in acute myeloid leukemia (AML). AML patients with DNMT3A R882 mutation are usually resistant to daunorubicin treatment; however, the associated mechanism is still unclear. Therefore, it is urgent to investigate daunorubicin resistance in AML patients with DNMT3A R882 mutant.

Method
AML cell lines with DNMT3A-wild type (DNMT3A-WT), and DNMT3A-Arg882His (DNMT3A-R882H) mutation were constructed to investigate the role of DNMT3A R882H mutation on cell proliferation, apoptosis and cells’ sensitivity to Danunorubin. Bioinformatics was used to analyze the role of nuclear factor-E2-related factor (NRF2) in AML patients with DNMT3A R882 mutation. The regulatory mechanism of DNMT3A R882H mutation on NRF2 was studied by Bisulfite Sequencing and CO-IP. NRF2 inhibitor Brusatol (Bru) was used to explore the role of NRF2 in AML cells carried DNMT3A R882H mutation.

Results
AML cells with a DNMT3A R882H mutation showed high proliferative and anti-apoptotic activities. In addition, mutant cells were less sensitive to daunorubicin and had a higher NRF2 expression compared with those in WT cells. Furthermore, the NRF2/NQO1 pathway was activated in mutant cells in response to daunorubicin treatment. DNMT3A R882H mutation regulated the expression of NRF2 via influencing protein stability rather than decreasing methylation of NRF2 promoter. Also, NRF2/NQO1 pathway inhibition improved mutant cells’ sensitivity to daunorubicin significantly.

Conclusion
Our findings identified NRF2 as an important player in the regulation of cell apoptosis through which helps mediate chemoresistance to daunorubicin in AML cells with DNMT3A R882H mutation. Targeting NRF2 might be a novel therapeutic approach to treat AML patients with a DNMT3A R882H mutation.
A narrative review of the moderating effects and repercussion of exercise intervention on osteoporosis: ingenious involvement of gut microbiota and its metabolites
Authors: Zhang Yuan-Wei , Cao Mu-Min , Li Ying-Juan , Chen Xiang-Xu , Yu Qian , Rui Yun-Feng 
Published: October 2022

AbstractOsteoporosis (OP) is a systemic bone disease characterized by the decreased bone mass and destruction of bone microstructure, which tends to result in the enhanced bone fragility and related fractures, as well as high disability rate and mortality. Exercise is one of the most common, reliable and cost-effective interventions for the prevention and treatment of OP currently, and numerous studies have revealed the close association between gut microbiota (GM) and bone metabolism recently. Moreover, exercise can alter the structure, composition and abundance of GM, and further influence the body health via GM and its metabolites, and the changes of GM also depend on the choice of exercise modes. Herein, combined with relevant studies and based on the inseparable relationship between exercise intervention-GM-OP, this review is aimed to discuss the moderating effects and potential mechanisms of exercise intervention on GM and bone metabolism, as well as the interaction between them.
Attitudes towards human milk banking among native turkish and refugee women residing in a rural region of Turkey: a mixed-methods approach
Authors: Varer Akpinar Ceren , Mandiracioglu Aliye , Ozvurmaz Safiye , Adana Filiz , Koc Nazife , Kurt Fatma 
Published: October 2022

Abstract
Background
Human milk banks (HMB) play an essential role by providing human milk to infants who would otherwise not be able to receive mother’s milk. There is currently no donor milk bank in Turkey. For any new health intervention to be successful, determining its acceptability is a vital first step. This study intends to determine the opinions, knowledge, and attitudes of native Turkish and refugee women living in Çeştepe, Aydın, a rural area in Turkey, about HMB.

Methods
A population-based cross-sectional, mixed-methods study was conducted. Qualitative study data were collected through in-depth interviews with 33 women, and quantitative study data were collected using a questionnaire. A total of 271 women in the region were included in the study. Qualitative data were thematically analyzed and then a conceptual framework was created. Logistic regression was performed for quantitative data.

Results
Fifty-seven point nine per cent of the women were willing to donate breast milk, whereas only 27.7% were willing to use donor milk for their babies. Religious concerns, fear of infectious diseases, and distrust in people they did not know were among the reasons for the negative attitudes of the women. Fear of infectious diseases was mentioned specifically by native Turkish women, and religious concerns were reported both by native Turkish and refugee women. The importance of breast milk and religion were among the reasons for positive attitudes. Additionally, odds of having a positive attitude were 4.19 times higher in homemaker women (95% CI 2.0, 8.76); 4.77 times higher in women with three or more children (95% CI 1.25, 8.15); 6.12 times higher in women who had a positive attitude towards wet nursing (95% CI 3.14, 9.63); and 2.68 times higher in those who had previously heard about human milk banking (95% CI 1.24, 5.79).

Conclusion
Attitudes towards HMB are affected by religion, cultural beliefs, and concerns about the safety of breast milk in HMBs. Refugees and native Turkish women are found to have similar religious concerns. These findings should be taken into consideration in human milk banking initiatives and in activities to increase acceptance by the public.
Pitfalls in the surgical treatment of undiagnosed lung lesions and cystic pulmonary hydatidosis
Authors: Yaldız Demet , Batıhan Güntuğ , Ceylan Kenan Can , Yaldız Sadık , Susam Seher 
Published: October 2022

Abstract
Background
Hydatid cysts can mimic many lung pathologies radiologically, as well as some malignant or benign lung tumors may show hydatid cyst-like radiological features. The aim of our study is to present our clinical experience and recommendations by analyzing the cases that create diagnostic difficulties by presenting a common radiological pattern with a pulmonary hydatid cyst.

Methods
The patients who were operated on with a preliminary diagnosis of hydatid cyst but were diagnosed differently, and who were operated on with different prediagnoses and unexpectedly diagnosed with hydatid cyst were included in the study. The clinical and radiological features of the patients were documented, and the features of the cases that could cause difficulties in diagnosis and treatment for the surgeon were revealed.

Results
A total of 20 patients who were radiologically suggestive of hydatid cyst but were diagnosed differently or unexpectedly diagnosed as hydatid cyst were included in the study. Lung cancer, bronchogenic cyst, or bronchiectasis were detected in 13 patients who were radiologically suggestive of hydatid cyst. There were 7 patients who were diagnosed with hydatid cysts, although they did not have specific radiological findings.

Conclusions
While hydatid cysts can mimic many lung pathologies, many benign or malign parenchymal lung pathologies may exhibit hydatid cyst-like radiological features. Therefore, in regions where a hydatid cyst is endemic, the surgeon should consider all possibilities while managing the cases.
Clinical registration number: Institutional Review Board of the Dr Suat Seren Chest Diseases and Chest Surgery Education and Research Center (No. 49109414-604.02).
Sharing is caring: a call for a new era of rare disease research and development
Authors: Denton Nathan , Mulberg Andrew E. , Molloy Monique , Charleston Samantha , Fajgenbaum David C. , Marsh Eric D. , Howard Paul 
Published: October 2022

AbstractScientific advances in the understanding of the genetics and mechanisms of many rare diseases with previously unknown etiologies are inspiring optimism in the patient, clinical, and research communities and there is hope that disease-specific treatments are on the way. However, the rare disease community has reached a critical point in which its increasingly fragmented structure and operating models are threatening its ability to harness the full potential of advancing genomic and computational technologies. Changes are therefore needed to overcome these issues plaguing many rare diseases while also supporting economically viable therapy development. In “Data silos are undermining drug development and failing rare disease patients (Orphanet Journal of Rare Disease, Apr 2021),” we outlined many of the broad issues underpinning the increasingly fragmented and siloed nature of the rare disease space, as well as how the issues encountered by this community are representative of biomedical research more generally. Here, we propose several initiatives for key stakeholders - including regulators, private and public foundations, and research institutions - to reorient the rare disease ecosystem and its incentives in a way that we believe would cultivate and accelerate innovation. Specifically, we propose supporting non-proprietary patient registries, greater data standardization, global regulatory harmonization, and new business models that encourage data sharing and research collaboration as the default mode. Leadership needs to be integrated across sectors to drive meaningful change between patients, industry, sponsors, and academic medical centers. To transform the research and development landscape and unlock its vast healthcare, economic, and scientific potential for rare disease patients, a new model is ultimately the goal for all.
Extracorporeal versus conventional cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: a secondary analysis of the Prague OHCA trial
Authors: Rob Daniel , Smalcova Jana , Smid Ondrej , Kral Ales , Kovarnik Tomas , Zemanek David , Kavalkova Petra , Huptych Michal , Komarek Arnost , Franek Ondrej , Havranek Stepan , Linhart Ales , Belohlavek Jan 
Published: October 2022

AbstractBackgroundSurvival rates in refractory out-of-hospital cardiac arrest (OHCA) remain low with conventional advanced cardiac life support (ACLS). Extracorporeal life support (ECLS) implantation during ongoing resuscitation, a method called extracorporeal cardiopulmonary resuscitation (ECPR), may increase survival. This study examined whether ECPR is associated with improved outcomes.MethodsPrague OHCA trial enrolled adults with a witnessed refractory OHCA of presumed cardiac origin. In this secondary analysis, the effect of ECPR on 180-day survival using Kaplan–Meier estimates and Cox proportional hazard model was examined.ResultsAmong 256 patients (median age 58 years, 83% male) with median duration of resuscitation 52.5 min (36.5–68), 83 (32%) patients achieved prehospital ROSC during ongoing conventional ACLS prehospitally, 81 (32%) patients did not achieve prehospital ROSC with prolonged conventional ACLS, and 92 (36%) patients did not achieve prehospital ROSC and received ECPR. The overall 180-day survival was 51/83 (61.5%) in patients with prehospital ROSC, 1/81 (1.2%) in patients without prehospital ROSC treated with conventional ACLS and 22/92 (23.9%) in patients without prehospital ROSC treated with ECPR (log-rankp < 0.001). After adjustment for covariates (age, sex, initial rhythm, prehospital ROSC status, time of emergency medical service arrival, resuscitation time, place of cardiac arrest, percutaneous coronary intervention status), ECPR was associated with a lower risk of 180-day death (HR 0.21, 95% CI 0.14–0.31;P < 0.001).ConclusionsIn this secondary analysis of the randomized refractory OHCA trial, ECPR was associated with improved 180-day survival in patients without prehospital ROSC.Trial registration: ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.
VoiceS: voice quality after transoral CO2 laser surgery versus single vocal cord irradiation for unilateral stage 0 and I glottic larynx cancer—a randomized phase III trial
Authors: Reinhardt Philipp , Giger Roland , Seifert Eberhard , Shelan Mohamed , Riggenbach Elena , Terribilini Dario , Joosten Andreas , Schanne Daniel H. , Aebersold Daniel M. , Manser Peter , Dettmer Matthias S. , Simon Christian , Ozsahin Esat M. , Moeckli Raphaël , Limacher Andreas , Caparrotti Francesca , Nair Deepa , Bourhis Jean , Broglie Martina A. , Al-Mamgani Abrahim , Elicin Olgun 
Published: October 2022

Abstract
Background
Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap.

Methods
In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness – breathiness – hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported.

Discussion
To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC.

Trial registration
ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506
A protocol for developing core outcome sets for laparoscopic hiatal hernia repair
Authors: Liu Xiaoli , Ma Qiuyue , Chen Jie , Yang Huiqi 
Published: October 2022

Abstract
Background
Hiatal hernias negatively damage patients’ health and life quality. Laparoscopic hiatal hernia repair is currently the gold standard for the treatment of hiatal hernia (LHHR). Numerous clinical trials on laparoscopic hiatal hernia repair have been done, but the published findings are highly variable due to the lack of unique outcome sets. Basic outcome sets have ever been established over the previous decade for a few procedures, but not for hiatal hernia repair yet. This protocol outlines the procedure to develop a core outcome set for laparoscopic hiatal hernia repair COS-LHHR). COS-LHHR will provide a unique criteria for clinical investigations.

Methods
This study will be conducted in four phases: (1) scoping reviews of existing qualitative studies and outcome reporting in randomized controlled trials to develop a list of potential outcome domains; (2) qualitative interviews with patients to explore the impact of laparoscopic hiatal hernia repair and the outcomes that they care most; (3) a multi-round e-Delphi study to achieve preliminary consensus on the core outcome set; and (4) an evidence-based consensus on a core outcome set will be achieved through a structured group consensus meeting, recommending best assessment outcome sets.

Discussion
The development the COS-LHHR will guide clinical research of laparoscopic hiatal hernia repair with unique outcome assessment. This would improve comparative analyses among studies.
Smartphone-RCCT: an online repository of randomized controlled clinical trials of smartphone applications for chronic conditions
Authors: Barth Jürgen , Wang Jiani , Lopez-Alcalde Jesus , Kramm Christoph , Pach Daniel , Álvarez-Díaz Noelia , Grifol-Clar Eulàlia , Witt Claudia M. 
Published: October 2022

Abstract
Background
Chronic health conditions have a big impact on disability, morbidity, and mortality worldwide. Smartphone health applications (apps) can improve the health of patients with chronic conditions and enhance the quality and efficiency of healthcare. The number of randomized controlled trials (RCTs) of smartphone health apps is increasing, but a collection of the available evidence into a single database is still missing. The purpose of this study is to describe Smartphone-RCCT, which is an in-progress database of RCTs of smartphone apps for chronic conditions.

Methods
For a study to be included in the database, the following criteria had to be met: (a) RCT published in a peer-reviewed journal; (b) population: adult study participants with one or several chronic conditions that represent the main health problem addressed by the study intervention; (c) intervention: smartphone health app used by the patient; (d) comparator: any control condition; (e) outcomes: any patient-reported health outcome (studies exclusively measuring the patients’ knowledge about the chronic conditions or their satisfaction with the smartphone app were excluded); (f) sample size: at least 15 participants per study arm. We searched in electronic databases and other resources to identify relevant studies. Two reviewers selected the studies and extracted data independently. Annual updates are planned.

Results
The proposed database is called Smartphone-RCCT, an open-access repository collecting bibliographic references and important characteristics of RCTs of smartphone apps for chronic conditions. The database is available for free in Open Science Framework (OSF): https://osf.io/nxerf/. To date, it includes 70 trials. Their references can be exported to standard reference management software and the extracted data is available in a Microsoft Excel file.

Conclusions
Smartphone-RCCT is the first systematic open-access database collecting peer-reviewed publications of RCTs of smartphone apps for patients with chronic conditions. The database accelerates the delivery of evidence-based information in a dynamic research field. It represents an essential resource for different stakeholders, such as professionals working in evidence synthesis, meta-epidemiological studies, or planning an RCT.
Efficacy of platelet-rich plasma impregnation for unidirectional porous β-tricalcium phosphate in lateral lumbar interbody fusion: study protocol for a prospective controlled trial
Authors: Sato Kosuke , Funayama Toru , Noguchi Hiroshi , Asada Tomoyuki , Kono Mamoru , Eto Fumihiko , Shibao Yosuke , Miura Kosei , Kikuchi Naoya , Yoshioka Tomokazu , Takahashi Hiroshi , Koda Masao , Yamazaki Masashi 
Published: October 2022

Abstract
Background
The use of platelet-rich plasma has been increasing in spinal fusion surgery. However, the efficacy of platelet-rich plasma in lateral lumbar interbody fusion is unclear. In Japan, Affinos,® (Kuraray Co., Tokyo, Japan), a β-tricalcium phosphate artificial bone, has been increasingly used for spinal fusion. The purpose of this trial is to demonstrate whether Affinos® impregnated with platelet-rich plasma can achieve a higher fusion rate and better clinical outcomes than Affinos® alone.

Methods
The current study is a prospective randomized controlled trial. This trial will include consecutive patients scheduled for lateral lumbar interbody fusion. An intervertebral cage for lateral lumbar interbody fusion has two spaces for bone grafts. As a consequence, two bone grafts are inserted at each intervertebral level. In this study, an artificial bone with platelet-rich plasma will be inserted into one space, and an artificial bone without platelet-rich plasma will be inserted into the other space. We will compare the fusion rates between the bone grafts with and without platelet-rich plasma. Our primary endpoint will be the interbody fusion rate at 1 year after surgery.

Discussion
This trial will verify the efficacy of platelet-rich plasma with Affinos® for bony fusion in lateral lumbar interbody fusion. It will also provide substantial evidence for the effectiveness and safety of platelet-rich plasma in spinal fusion surgery.

Trial registration
Japan Registry of Clinical Trials (jRCT) jRCTb032200199. First registered on 13 November 2020. jRCT is approved as a member of the Primary Registry Network of WHO ICTRP.
Seasonal distribution of Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi in Tibetan sheep in Qinghai, China
Authors: Yang Fan , Ma Li , Gou Jing-min , Yao Hui-zhong , Ren Mei , Yang Bing-ke , Lin Qing 
Published: October 2022

Abstract
Background
Cryptosporidium spp., Giardia duodenalis and Enterocytozoon bieneusi can cause important intestinal diseases in ruminants. However, data on the distribution of these three protozoan pathogens in Tibetan sheep are limited.

Methods
We collected 761 fecal samples from Tibetan sheep across four seasons in Qinghai Province, China, and screened the samples for Cryptosporidium spp., G. duodenalis and E. bieneusi using PCR-based sequence analysis of the genes encoding 18S ribosomal RNA, triosephosphate isomerase and the internal transcribed spacer, respectively.

Results
The positivity rates of Cryptosporidium spp., G. duodenalis and E. bieneusi in Tibetan sheep were 3.68% (28/761 samples), 1.58% (12/761) and 6.44% (49/761), respectively. Four species of Cryptosporidium were identified: C. xiaoi (n = 13 samples), C. ubiquitum (n = 8), C. bovis (n = 6) and C. ryanae (n = 1). Two G. duodenalis assemblages, namely the A (n = 2 samples) and E (n = 10) assemblages, were detected. Five zoonotic E. bieneusi genotypes were found: BEB6 (n = 21 samples), COS-I (n = 14), CHS3 (n = 11) and CGS1 (n = 2) from group 2, and PIGEBITS5 (n = 1) from group 1. Geographic differences in the distribution of E. bieneusi, and seasonal differences for all the three protozoan pathogens were noted.

Conclusions
Our results elucidate the prevalence and genetic diversity of these three pathogens in Tibetan sheep across different regions and seasons, including zoonotic pathogens such as C. ubiquitum, C. ryanae, G. duodenalis assemblage A and five genotypes of E. bieneusi.

Graphical Abstract