bluuebunny/crossref_metadata_2025_split huggingface dataset:
Researching, co-creating and testing innovations in paper-based health information systems (PHISICC) to support health workers’ decision-making: protocol of a multi-country, transdisciplinary, mixed-methods research programme in three sub-Saharan countries
Authors: Bosch-Capblanch Xavier , O’Donnell David , Krause L. Kendall , Auer Christian , Oyo-Ita Angela , Samba Mamadou , Matsinhe Graça , Garba Abdullahi Bulama , Rodríguez Damaris , Zuske Meike , Njepuome Anthonia Ngozi , Lee Sofia Micael Mandjate , Ross Amanda , Gajewski Suzanne , Muloliwa Artur Manuel , Yapi Richard B. , Brown David W. 
Published: August 2021

AbstractBackgroundHealth information systems are crucial to provide data for decision-making and demand for data is constantly growing. However, the link between data and decisions is not always rational or linear and the management of data ends up overloading frontline health workers, which may compromise quality of healthcare delivery. Despite limited evidence, there is an increasing push for the digitalization of health information systems, which poses enormous challenges, particularly in remote, rural settings in low- and middle-income countries. Paper-based tools will continue to be used in combination with digital solutions and this calls for efforts to make them more responsive to local needs. Paper-based Health Information Systems in Comprehensive Care (PHISICC) is a transdisciplinary, multi-country research initiative to create and test innovative paper-based health information systems in three sub-Saharan African countries.Methods/DesignThe PHISICC initiative is being carried out in remote, rural settings in Côte d’Ivoire, Mozambique and Nigeria through partnership with ministries of health and research institutions. We began with research syntheses to acquire the most up-to-date knowledge on health information systems. These were coupled with fieldwork in the three countries to understand the current design, patterns and contexts of use, and healthcare worker perspectives. Frontline health workers, with designers and researchers, used co-creation methods to produce the new PHISICC tools. This suite of tools is being tested in the three countries in three cluster-randomized controlled trials. Throughout the project, we have engaged with a wide range of stakeholders and have maintained the highest scientific standards to ensure that results are relevant to the realities in the three countries.DiscussionWe have deployed a comprehensive research approach to ensure the robustness and future policy uptake of findings. Besides the innovative PHISICC paper-based tools, our process is in itself innovative. Rather than emphasizing the technical dimensions of data management, we focused instead on frontline health workers’ data use and decision-making. By tackling the whole scope of primary healthcare areas rather than a subset of them, we have developed an entirely new design and visual language for a suite of tools across healthcare areas. The initiative is being tested in remote, rural areas where the most vulnerable live.
Developing PspCas13b-based enhanced RESCUE system, eRESCUE, with efficient RNA base editing
Authors: Li Guo , Wang Yihan , Li Xiangyang , Wang Yuzhe , Huang Xingxu , Gao Jianen , Hu Xiaoxiang 
Published: August 2021

AbstractRNA base editing is potential for cellular function research and genetic diseases treating. There are two main RNA base editors, REPAIR and RESCUE, for in vitro use. REPAIR was developed by fusing inactivated Cas13 (dCas13) with the adenine deaminase domain of ADAR2, which efficiently performs adenosine-to-inosine (A-to-I) RNA editing. RESCUE, which performs both cytidine-to-uridine (C-to-U) and A-to-I RNA editing, was developed by fusing inactivated Cas13 (dCas13) with the evolved ADAR2. However, the relatively low editing efficiency of the RESCUE system limits its broad application. Here, we constructed an enhanced RESCUE (eRESCUE) system; this dPspCas13b-RESCUE-NES system was generated by fusing inactivated PspCas13b with the evolved ADAR2. We determined the endogenous mRNA A-to-I and C-to-U editing efficiency mediated by the dPspCas13b-RESCUE-NES system in HEK-293T cells. This new RNA base editor was then used to induce 177Ser/Gly conversion of inhibitor kappa B kinase β (IKKβ) by changing the genetic code from AGU to GGU. The results showed that the eRESCUE editor mediates more efficient A-to-I and C-to-U RNA editing than the RESCUE RNA editor, as was previously reported. The 177Ser/Gly conversion of IKKβ, accomplished by converting the genetic code from AGU to GGU, resulted in a decrease in the phosphorylation of IKKβ and downregulation of downstream IKKβ-related genes. In summary, we developed a more efficient RNA base editor, eRESCUE, which may provide a useful tool for biomedical research and genetic disease treatment.
Anti-inflammatory and -apoptotic effects of a long-term herbal extract treatment on DSS-induced colitis in mice fed with high AGEs-fat diet
Authors: Azizian-Farsani Fatemeh , Osuchowski Marcin , Abedpoor Navid , Forootan Farzad Seyed , Derakhshan Maryam , Nasr-Esfahani Mohammad Hossein , Sheikhha Mohammad Hasan , Ghaedi Kamran 
Published: August 2021

Abstract
Background
Obesity is associated with many comorbidities including inflammatory bowel disease (IBD). We investigated prophylactic effects of an herbal extract (HE) on the DSS-induced colitis mice challenged with high AGEs-fat diet 60% (HFD).

Methods
Six-week-old C57BL/6 male mice were fed with either HFD (8 groups, 6 mice in each group), or normal diet (ND) (8 groups, 6 mice in each group). After 6 weeks, animals received HE (combination of turmeric, ginger, boswellia and cat’s claw extract) for 7 weeks in three doses (high dose (0.6 mg/g); low dose (0.15 mg/g) and mid dose (0.3 mg/g)). Next, mice were subjected to 2.5% DSS in drinking water. Control mice received ND and instead of HE and DSS they received distilled water. Obesity index markers were determined, H&E staining and TUNEL assay evaluated apoptosis. Colonic expressions of IL-6, RAGE, AGER1, Sirt1, Bax, Bcl2, ZO-1 and P53 were determined.

Results
HE ameliorated colitis in HFD mice by reducing colonic myeloperoxidase activity (by 2.3-fold), macrophage accumulation (by 2.6-fold) and mRNA expression of IL-6 (by 2.3-fold) in HFD mice. Moreover, HE restored ZO-1 (by 2.7-fold), prevented apoptosis and maintained immune homeostasis. HE reduced activation of NF-κB protein (by 1.3-fold) through decreasing RAGE (by 1.93-fold) and up-regulation of Sirt1 (by 7.71-fold) and prevented down-regulation of DDOST (by 6.6-fold) in HFD mice.

Conclusions
HE ameliorated colitis in prophylactic in HFD mice and it was, at least partly, due to the restoration of the gut integrity, suppression of inflammation and apoptosis via modulation of colonic Sirt1, RAGE and DDOST signaling.

Graphic abstract
Assessing the evidence on the differential impact of menthol versus non-menthol cigarette use on smoking cessation in the U.S. population: a systematic review and meta-analysis
Authors: Kim Mimi M. , Curtin Geoffrey M. 
Published: August 2021

AbstractBackgroundThe potential impact of menthol versus non-menthol cigarette use on smoking behaviors is an intensely scrutinized topic in the public health arena. To date, several general literature reviews have been conducted, but findings and conclusions have been discordant. This systematic review followed PRISMA guidelines to examine the Key Question, “Does menthol cigarette use have a differential impact on smoking cessation compared with non-menthol cigarette use?”MethodsSix databases—Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, MEDLINE, Embase and PsycInfo—were queried from inception to June 12, 2020. Articles comparing menthol versus non-menthol cigarette smokers in terms of at least one predefined smoking cessation outcome were included. Risk of bias was assessed using the Agency for Healthcare Research and Quality Evidence-Based Practice Center approach. A random-effects model utilizing the DerSimonian and Laird method to pool adjusted odds ratio was applied. Variations among pooled studies were assessed using Cochran’s Q statistic, and heterogeneity was quantified using the inconsistency index (I2).ResultsForty-three demographically adjusted studies (22 rated “good”, 20 rated “fair”, and one study rated “poor” individual study quality) comparing menthol and non-menthol smokers were qualitatively synthesized across the following measures (study count; strength of evidence): duration of abstinence (2; low); quit attempts (15; insufficient); rate of abstinence/quitting (29; moderate); change in smoking quantity/frequency (5; insufficient); and, return to smoking/relapse (2; insufficient). Overall, the qualitative synthesis failed to show a consistent trend for an association between menthol cigarette use and smoking cessation across outcomes. Meta-analyses found no difference between menthol and non-menthol cigarette use and either quit attempts or abstinence.ConclusionsGiven the lack of consistency or statistical significance in the findings—combined with a “low” overall strength of evidence grade, based on deficiencies of indirectness and inconsistency—no consistent or significant associations between menthol cigarette use and smoking cessation were identified. Recommendations for future studies include increased focus on providing longitudinal, adjusted data collected from standardized outcome measures of cessation to better inform long-term smoking cessation and menthol cigarette use. Such improvements should also be further considered in more methodologically rigorous systematic reviews characterized by objectivity, comprehensiveness, and transparency with the ultimate objective of better informing public health and policy decision making.
Clinical and radiographic outcomes of hybrid graft in patients with Modic changes undergoing transforaminal lumbar interbody fusion
Authors: Jiao Jiaxun , Li Jiaqi , Luo Yun , Zhang Wei 
Published: August 2021

Abstract
Background
This retrospective study aimed to analyze the influence of Modic changes (MCs) on the clinical and radiographic outcomes of transforaminal lumbar interbody fusion with hybrid graft.

Methods
Clinical data of 89 patients with Modic changes who underwent single-segment transforaminal lumbar interbody fusion between January 2015 and January 2019 at our institution were analyzed. Patients were divided into three groups: the MCs-0 group (no endplate changes; used as the control group), the MCs-1 group, and the MCs-2 group. Clinical and radiological parameters were compared between the three groups.

Results
There were no significant between-group differences in age (P = 0.216), sex (P = 0.903), body mass index (P = 0.805), smoking (P = 0.722), diagnosis (P = 0.758), surgical level (P = 0.760), blood loss (P = 0.172), operative time (P = 0.236), or follow-up (P = 0.372). Serum C-reactive protein level and erythrocyte sedimentation rate in the MCs-1 and MCs-2 groups were significantly higher than those in the MCs-0 group on the third and seventh days (P < 0.05). Postoperative radiographic parameters were significantly higher than preoperative parameters in all 3 groups (P < 0.05). Visual analog scale scores for low back pain in the MCs-0 and MCs-2 groups were significantly different from those in the MCs-1 group (P < 0.05). However, there were no significant between-group differences with respect to Oswestry Disability Index scores or visual analog scale scores for leg pain.

Conclusion
In this study, Modic changes had no impact on fusion rates and clinical outcomes of transforaminal lumbar interbody fusion with hybrid graft (autologous local bone graft plus allogeneic freeze-dried bone graft). However, MCs-1 increased the risk of cage subsidence and showed superior outcomes in terms of visual analog scale scores for low back pain.
Mannose supplementation in PMM2-CDG
Authors: Taday Roman , Park Julien H. , Grüneberg Marianne , DuChesne Ingrid , Reunert Janine , Marquardt Thorsten 
Published: August 2021

AbstractIn this response to the letter by Witters et al., we refer to the authors' arguments regarding spontaneous enhancement of glycosylation and the claim, that mannose has no place in the treatment of PMM2-CDG. Our paper “Dietary mannose supplementation in phosphomannomutase 2 deficiency (PMM2-CDG)” has shown that further investigation of mannose in PMM2-CDG is worthwhile alongside other treatment options and should not be dismissed off-hand without the willingness to prove or disprove it in controlled prospective clinical trials.
Phosphorylation of NF-κBp65 drives inflammation-mediated hepatocellular carcinogenesis and is a novel therapeutic target
Authors: Xu Xuan , Lei Yiming , Chen Lingjun , Zhou Haoxiong , Liu Huiling , Jiang Jie , Yang Yidong , Wu Bin 
Published: August 2021

Abstract
Background
Nuclear factor­κB (NF-κB) plays a vital role in hepatocellular carcinoma (HCC). β-arrestin1 (ARRB1) has been proved to enhance the activity of NF-κBp65, and our previous study indicated that ARRB1 promotes hepatocellular carcinogenesis and development of HCC. However, it remains unknown whether p65 is involved in hepatocellular carcinogenesis through the ARRB1-mediated pathway.

Methods
The levels of NF-κBp65 and NF-κBp65 phosphorylation (p-p65) were assessed in including normal liver, primary HCC and paired paracancerous tissues. Liver-specific p65 knockout mice were used to examine the role of p65 and p-p65 in hepatocarcinogenesis. The mechanism of NF-κBp65 and p-p65 in hepatocarcinogenesis via ARRB1 was also studied both in vitro and in vivo.

Results
Phosphorylation of NF-κBp65 was markedly upregulated in inflammation-related HCC patients and was significantly increased in mouse hepatic inflammation models, which were induced by tetrachloromethane (CCl4), diethylnitrosamine (DEN), TNF-α, as well as DEN-induced HCC. Hepatocyte-specific p65-deficient mice markedly decreased in the HCC incidence and size of tumours by the repressing of the proliferation of malignant cells in a DEN-induced HCC model. Furthermore, ARRB1 directly bounds p65 to promote the phosphorylation of NF-κBp65 at ser536, resulted in cell malignant proliferation through GSK3β/mTOR signalling.

Conclusion
The data demonstrated that phosphorylation of NF-κBp65 drives hepatocellular carcinogenesis in response to inflammation-mediated ARRB1, and that inhibition of the phosphorylation of NF-κBp65 restrains the hepatocellular carcinogenesis. The results indicate that phosphorylation of NF-κBp65 is a novel therapeutic target for HCC.
Can expelled cells/debris from a developing embryo be used for PGT?
Authors: Aizer Adva , Harel-Inbar Noa , Shani Hagit , Orvieto Raoul 
Published: August 2021

Abstract
Background
Preimplantation genetic testing (PGT) is offered to a wide range of structural and numerical chromosomal imbalances, with PGT- polymerase chain reaction (PCR), as the method of choice for amplifying the small DNA content achieved from the blastomere biopsy or trophectoderm (TE) biopsy, that might have a detrimental impact on embryonic implantation potential. Since human embryos cultured until Day-5–6 were noticed to expel cell debris/ fragments within the zona pellucida, we aimed to examine whether these cell debris/ fragments might be used for PGT, as an alternative to embryo biopsy.

Methods
Blastocysts, which their Day-3 blastomere biopsy revealed an affected embryo with single-gene defect, and following hatching leaved cell debris/fragments within the zona pellucida were analyzed. Each blastocyst and its corresponding cell debris/fragments were separated and underwent the same molecular analysis, based on multiplex PCR programs designed for haplotyping using informative microsatellites markers. The main outcome measure was the intra-embryo congruity of Day-3 blastomere biopsy and its corresponding blastocyst and cell debris/fragments.

Results
Fourteen affected embryos from 9 women were included. Only 8/14 (57.2%) of embryos demonstrated congruent molecular genetic results between Day-3 embryo and its corresponding blastocyst and cell debris/fragments. In additional 6/14 (42.8%) embryos, molecular results of the Day-3 embryos and their corresponding blastocysts were congruent, while the cell debris/fragments yielded no molecular diagnoses (incomplete diagnoses).

Conclusions
It might be therefore concluded, that in PGT cycles, examining the cell debris/fragments on Day-4, instead of Day-3 blastomere or Day-5 TE biopsies, is feasible and might avoid embryo biopsy with its consequent detrimental effect on embryos’ implantation potential. Whenever the latter results in incomplete diagnosis, TE biopsy should be carried out on Day-5 for final genetic results. Further large well-designed studies are required to validate the aforementioned PGT platform.
Association between the rs615563 variant of PCSK9 gene and circulating lipids and Type 2 diabetes
Authors: Taghizadeh Jazdani Samira , Shahbazian Hajieh Bibi , Cheraghian Bahman , Jalali Mohammad Taha , Mohammadtaghvaei Narges 
Published: August 2021

Abstract
Objective
Many different genetic variants of proprotein convertase subtilisin kexin 9 (PCSK9) are related to the serum levels of cholesterol and LDL cholesterol (LDL-C). The rs615563 variant of PCSK9 (a gain-of-function mutation) is associated with increased triglycerides and cholesterol levels, but its association with the incidence of diabetes is not well defined. This study aimed to investigate the relationship between the PCSK9 rs615563 variant with the incidence of type 2 diabetes. The data reported in this study are based on subsamples from a 5-year (2009–2014) cohort study of the adult population (590 subjects) aged 20 years and older. The rs615563 polymorphism was genotyped using polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) analysis.

Results
The distribution of PCSK9 rs615563 genotypes was not significantly different between the diabetic and non-diabetic individuals. The incidence of diabetes after five-years of follow-up was not different between the genotypes. Our findings also showed no significant relationship between this polymorphism and serum lipid parameters. The data extracted from our cohort study do not support the findings that the gain-of-function mutations of PCSK9 predispose to the incidence of type 2 diabetes.
Human umbilical cord mesenchymal stem cells reduce oxidative damage and apoptosis in diabetic nephropathy by activating Nrf2
Authors: Nie Ping , Bai Xue , Lou Yan , Zhu Yuexin , Jiang Shan , Zhang Lina , Tian Na , Luo Ping , Li Bing 
Published: August 2021

Abstract
Background
Mesenchymal stem cells (MSCs) have a therapeutic effect on diabetic nephropathy (DN) but the underlying mechanism remains unclear. This study was conducted to investigate whether human umbilical cord-MSCs (hUCMSCs) can induce oxidative damage and apoptosis by activating Nrf2.

Methods
We used a type 2 diabetic rat model and a high-glucose and fat-stimulated human glomerular mesangial cell (hGMC) model. Western blotting, RT-qPCR, and TUNEL staining were performed on animal tissues and cultured cells. Nuclear expression of Nrf2 was detected in the renal tissue. Furthermore, Nrf2 siRNA was used to examine the effects of hUCMSCs on hGMCs. Finally, the effect of hUCMSCs on the Nrf2 upstream signalling pathway was investigated.

Results
After treatment with hUCMSCs, Nrf2 showed increased expression and nuclear translocation. After Nrf2-specific knockout in hGMCs, the protective effect of hUCMSCs on apoptosis induced by high-glucose and fat conditions was reduced. Activation of the PI3K signalling pathway may be helpful for ameliorating DN using hUCMSCs.

Conclusions
hUCMSCs attenuated renal oxidative damage and apoptosis in type 2 diabetes mellitus and Nrf2 activation is one of the important mechanisms of this effect. hUCMSCs show potential as drug targets for DN.
Outcome of cancer patients considered for intensive care unit admission in two university hospitals in the Netherlands: the danger of delayed ICU admissions and off-hour triage decisions
Authors: van der Zee Esther N. , Benoit Dominique D. , Hazenbroek Marinus , Bakker Jan , Kompanje Erwin J. O. , Kusadasi Nuray , Epker Jelle L. 
Published: August 2021

Abstract
Background
Very few studies assessed the association between Intensive Care Unit (ICU) triage decisions and mortality. The aim of this study was to assess whether an association could be found between 30-day mortality, and ICU admission consultation conditions and triage decisions.

Methods
We conducted a retrospective cohort study in two large referral university hospitals in the Netherlands. We identified all adult cancer patients for whom ICU admission was requested from 2016 to 2019. Via a multivariable logistic regression analysis, we assessed the association between 30-day mortality, and ICU admission consultation conditions and triage decisions.

Results
Of the 780 cancer patients for whom ICU admission was requested, 332 patients (42.6%) were considered ‘too well to benefit’ from ICU admission, 382 (49%) patients were immediately admitted to the ICU and 66 patients (8.4%) were considered ‘too sick to benefit’ according to the consulting intensivist(s). The 30-day mortality in these subgroups was 30.1%, 36.9% and 81.8%, respectively. In the patient group considered ‘too well to benefit’, 258 patients were never admitted to the ICU and 74 patients (9.5% of the overall study population, 22.3% of the patients ‘too well to benefit’) were admitted to the ICU after a second ICU admission request (delayed ICU admission). Thirty-day mortality in these groups was 25.6% and 45.9%. After adjustment for confounders, ICU consultations during off-hours (OR 1.61, 95% CI 1.09–2.38, p-value 0.02) and delayed ICU admission (OR 1.83, 95% CI 1.00–3.33, p-value 0.048 compared to “ICU admission”) were independently associated with 30-day mortality.

Conclusion
The ICU denial rate in our study was high (51%). Sixty percent of the ICU triage decisions in cancer patients were made during off-hours, and 22.3% of the patients initially considered “too well to benefit” from ICU admission were subsequently admitted to the ICU. Both decisions during off-hours and a delayed ICU admission were associated with an increased risk of death at 30 days. Our study suggests that in cancer patients, ICU triage decisions should be discussed during on-hours, and ICU admission policy should be broadened, with a lower admission threshold for critically ill cancer patients.
A blockchain-based privacy-preserving 5G network slicing service level agreement audit scheme
Authors: Xiao Ke , Geng Ziye , He Yunhua , Xu Gang , Wang Chao , Tian Yutong 
Published: August 2021

AbstractNetwork slicing, as a key technique of 5G, provides a way that network operators can segment multiple virtual logic on the same physical network and each customer can order specific slicing which can meet his requirement of 5G service. The service level agreement of network slicing (NS-SLA) of 5G, as a business agreement signed between the network operators and the customers, specifies the relevant requirements for the 5G services provided by the network operators. However, the authenticity of auditing results may not be guaranteed and the customer’s data may be leaked in the existing NS-SLA audit scheme. In this paper, a blockchain-based 5G network slicing NS-SLA audit model is proposed to address the above problems. The blockchain is applied as a public platform and all the dual monitored service parameters will be stored on the blockchain to ensure the authenticity of data. A trapdoor order-revealing encryption algorithm is introduced to audit strategy, which can encrypt the monitored parameters, realize the comparison over ciphertexts and prevent the privacy of data from leaking. Besides, an NS-SLA audit smart contract is designed to implement the audit task and execute corresponding punishment strategies automatically. We make experiments to exam the cost of the blockchain-based system and the results found clear support for the feasibility of the proposed model.