bluuebunny/crossref_metadata_2025_split huggingface dataset:
Strain specific properties of Escherichia coli can prevent non-canonical amino acid misincorporation caused by scale-related process heterogeneities
Authors: Mayer Florian , Cserjan-Puschmann Monika , Haslinger Benedikt , Shpylovyi Anton , Dalik Thomas , Sam Christian , Hahn Rainer , Striedner Gerald 
Published: August 2022

Abstract
Background
Escherichia coli is one of the most important hosts for production of recombinant proteins in biopharmaceutical industry. However, when selecting a suitable production strain, it is often not considered that a lot of different sub-species exist, which can differ in their genotypes and phenotypes. Another important development step is the scale-up of bioprocesses with the particular challenge that heterogeneities and gradients occur at production scale. These in turn can affect the production organism and can have negative impact on the process and the product quality. Therefore, researchers developed scale-down reactors, which are used to mimic manufacturing conditions in laboratory scale. The main objectives of this study were to determine the extent to which scale-related process inhomogeneities affect the misincorporation of non-canonical amino acids into the recombinant target protein, which is an important quality attribute, and whether strain specific properties may have an impact.

Results
We investigated two industrially relevant E. coli strains, BL21(DE3) and HMS174(DE3), which produced an antigen binding fragment (Fab). The cells were cultivated in high cell density fed-batch mode at laboratory scale and under scale-down conditions. We demonstrated that the two host strains differ significantly with respect to norleucine misincorporation into the target protein, especially under heterogeneous cultivation conditions in the scale-down reactor. No norleucine misincorporation was observed in E. coli BL21(DE3) for either cultivation condition. In contrast, norleucine incorporation into HMS174(DE3) was already detectable in the reference process and increased dramatically in scale-down experiments. Norleucine incorporation was not random and certain positions were preferred over others, even though only a single codon exists. Differences in biomass and Fab production between the strains during scale-down cultivations could be observed as well.

Conclusions
This study has shown that E. coli BL21(DE3) is much more robust to scale-up effects in terms of norleucine misincorporation than the K12 strain tested. In this respect, BL21(DE3) enables better transferability of results at different scales, simplifies process implementation at production scale, and helps to meet regulatory quality guidelines defined for biopharmaceutical manufacturing.
The role of ferroptosis in esophageal cancer
Authors: Wang Zimin , Wu Sikai , Zhu Chengchu , Shen Jianfei 
Published: August 2022

AbstractEsophageal cancer is one of the most common cancers with high mortality rate around the world. Although the treatment strategy of this disease has made great progress, the prognosis of advanced patients is not ideal. Ferroptosis, a novel regulatory cell death model, that is different from traditional apoptosis and characterized by increased Fenton reaction mediated by intracellular free iron and lipid peroxidation of cell membrane. Ferroptosis has been proved to be closely linked to a variety of diseases, especially cancer. This review aims to summarize the core mechanism of ferroptosis in esophageal cancer, the regulation of ferroptosis signaling pathway and its current application. At the same time, we emphasize the potential and prospect of ferroptosis in the treatment of esophageal cancer. Collectively, targeting ferroptosis pathway may provide new insights into the diagnosis, treatment and prognosis of esophageal cancer.
Neoadjuvant chemotherapy followed by radical surgery reduces radiation therapy in patients with stage IB2 to IIA2 cervical cancer
Authors: Huang Yuhui , Chen Lei , Cai Jing , Yang Lu , Sun Si , Zhao Jing , Xiong Zhoufang , Wang Zehua 
Published: August 2022

Abstract
Background
To investigate whether carboplatin-liposomal paclitaxel neoadjuvant chemotherapy (NACT) benefits patients with locally advanced cervical cancer (LACC) through avoiding or delaying postoperative radiation.

Methods
A total of 414 patients with cervical cancer of International Federation of Gynecology and Obstetrics (FIGO 2009) stages IB2–IIA2 were included in the retrospective cohort study, who had received carboplatin-liposomal paclitaxel chemotherapy followed by radical surgery (NACT group) or primary radical surgery (PRS group) between 2007 and 2017 at our hospital. The baseline clinicopathological characteristics at diagnosis, postoperative pathological risk factors, and oncological outcomes after surgery, including postoperative radiation (as adjuvant treatment or treatment of recurrent diseases), progression-free survival (PFS), and overall survival (OS), were compared between the groups. Before treatment, the patients in the NACT group had significantly more advanced tumor stages and larger tumor sizes than those in the PRS group.

Results
The NACT reduced the tumor volumes remarkedly with a response rate of 62.4%, and the tumors in the NACT group were smaller than those in the PRS group when the patients were subjected to radical surgery. Furthermore, postoperative pathology examination revealed less frequent deep stromal invasion in the NACT group than in the PRS group. According to the presence of pathological risk factors for recurrence, 54.82% of women in the NACT group needed adjuvant radiotherapy, while 60.87% in the PRS group, and in fact, 33.00% of NACT patients and 40.09% of PRS patients received adjuvant radiation. In addition, 8.12% of NACT patients and 9.68% of PRS patients underwent radiotherapy after relapse. The cumulative postoperative radiation rate was significantly lower in the NACT group (P = 0.041), while the differences in 5-year OS and PFS were not statistically significant between the groups.

Conclusions
NACT reduces the pathological risk factors and the use of radiation without compromising survival in patients with LACC, which may protect younger patients from radiation-related side effects and subsequently improve the quality of life.

Trial registration
ISRCTN Registry, ISRCTN24104022
Evaluation of the appropriate use of chest CT-Scans in the diagnosis of hospitalized patients in shiraz teaching hospitals, Southern Iran
Authors: Kamrani Ramiz , Fallahi Mohammad Javad , Masoompour Seyed Masoom , Ghayumi Seiyed Mohammad Ali , Jalli Reza , Khederzadeh Sepideh , Erfani Amirhossein 
Published: August 2022

AbstractPurposeDuring recent years, overuse of medical imaging especially computed tomography has become a serious concern. We evaluated the suitable usage of chest computed tomography (CT)-scan, in patients hospitalized in emergency and medical wards of two teaching hospitals of Shiraz University of Medical Science.MethodsMedical records of 216 patients admitted in two major teaching hospitals (Namazi and Shahid Faghihi), who had undergone chest radiography and at least one type of chest CT were investigated. The clinical and paraclinical manifestations were independently presented to three pulmonologists and their opinion regarding the necessity and type of CT prescription were documented. Also, the patient’s history was presented to an expert chest radiologist and asked to rate the appropriateness of chest CT according to American colleague of radiologist (ACR) criteria.ResultsIn 127 cases (59%), at least 2 out of 3 pulmonologists had the same opinion on the necessity of performing CT scan regardless of CT scan type, in 89 cases (41%) the same CT type and in 38 (17.5%) cases other CT type was supposed. Based on ACR criteria, of total prescribed CTs, 49.5% were “usually not appropriate” and 31.5% of cases were “usually appropriate”. Among 109 pulmonary CT angiography, 54 (49.5%) was usually not appropriate base on ACR criteria, which was the most frequent inappropriate requested CT type.ConclusionConsidering the high rates of inappropriate utilization of chest CT scan in our teaching hospitals, implementation of the standard guideline at a different level and consulting with a pulmonologist, may prevent unnecessary chest CTs prescription and reduce harm to patients and the health system.
Effects of a brief pre-admission telephone reminder on no-show and dropout rates in substance use disorder treatment: a quasi-experimental study
Authors: Gallefoss Lisbeth Jensen , Gabrielsen Karin Berle , Haugland Siri Håvås , Clausen Thomas , Vederhus John-Kåre 
Published: August 2022

Abstract
Background
Appointment no-show and early dropout from treatment represent major challenges in outpatient substance use disorder treatment, adversely affecting clinical outcomes and health care productivity. In this quasi-experimental study, we examined how a brief reminder intervention for new patients before their first appointment affected treatment participation and retention. No-shows (not attending any sessions) and dropouts (discontinuation of initiated treatment because of three consecutively missed appointments) were compared between a period with pre-admission telephone calls (intervention) and a period without such reminders (non-intervention).

Methods
Participants were all eligible patients (N = 262) admitted to a Norwegian specialist clinic for substance use disorder treatment. We used the Chi-square test for the no-show analysis. Of the eligible patients, 147 were included in a subsequent dropout analysis. We used the number of visits up to 10 appointments as a measure for time to event. Group differences were analyzed using a Kaplan–Meier plot and the log-rank test. To control for relevant sociodemographic variables, as well as substance use and mental distress severity, we used Cox regression.

Results
No-show rates did not differ between the two periods (12% for non-intervention vs. 14% for intervention; χ2 = 0.20, p = 0.653). Of those consenting to participate in the dropout analysis (n = 147), 28 (19%) discontinued treatment within the time frame of 10 appointments, with no differences between the two periods (log-rank test = 0.328, p = 0.567). Controlling for baseline characteristics did not alter this finding. In fact, of the registered covariates at baseline, only higher education level was associated with attrition, linked to a reduced risk for dropout (hazard ratio = 0.85, 95% CI = 0.74–0.98, p = 0.025).

Conclusion
These findings do not provide support for the systematic use of a brief pre-admission telephone reminder in the current treatment setting.

Trial registration
The study was retrospectively registered 13 Jan 2021 at ClinicalTrials.gov, NCT04707599.
Barriers and facilitators to using aspirin for preventive therapy: a qualitative study exploring the views and experiences of people with Lynch syndrome and healthcare providers
Authors: Lloyd Kelly E. , Foy Robbie , Hall Louise H. , Ziegler Lucy , Green Sophie M. C. , Haider Zainab F. , Taylor David G. , MacKenzie Mairead , Smith Samuel G. 
Published: August 2022

Abstract
Background
The National Institute for Health and Care Excellence (NG151) recommends considering daily aspirin for people with Lynch syndrome to reduce colorectal cancer risk. However, deciding whether to initiate aspirin could be a complex decision for patients and their healthcare providers, as both the potential benefits and harms need to be considered.

Methods
We conducted semi-structured interviews to explore the barriers and facilitators to using aspirin for preventive therapy. We recruited 15 people with Lynch syndrome, and 23 healthcare providers across multiple professions in primary, and specialist care (e.g. clinical genetics) in the United Kingdom. Interview schedules were informed by the Theoretical Domains Framework.

Results
There were three themes: 1) Considering potential harms and benefits; 2) Healthcare pathway; 3) Patients’ level of interest in aspirin. All healthcare providers, across primary and specialist care, viewed general practitioners (GPs) as being responsible for prescribing and overseeing the use of aspirin. However, GPs were unfamiliar with aspirin for preventive therapy, and concerned about prescribing at higher doses (300-600 mg). To support decision-making, GPs wanted clarification from specialist clinicians on the evidence and dose to prescribe. Not all participants with Lynch syndrome received information on aspirin from their healthcare provider, and several were unsure who to discuss aspirin with. GPs were more inclined to prescribe aspirin for patients with expressed preferences for the medication, however several patients were uncertain and wanted further guidance.

Conclusions
Coordinated and multilevel strategies are needed, addressing the needs of both GPs and people with Lynch syndrome, to ensure consistent implementation of national guidance on aspirin for preventive therapy.
Identification of genetic variants related to metabolic syndrome by next-generation sequencing
Authors: Lee Sanghoo , Kim Seol-A , Hong Jeonghoon , Kim Yejin , Hong Gayeon , Baik SaeYun , Choi Kyeonghwan , Lee Mi-Kyeong , Lee Kyoung-Ryul 
Published: August 2022

Abstract
Background
Metabolic syndrome (MetS) is a cluster of conditions associated with glucose intolerance, hypertension, abdominal obesity, dyslipidemia, and insulin resistance that increase the risk of cardiovascular diseases (CVD) and type 2 diabetes (T2D). Since MetS is known as a complex symptom with a high incidence of genetic factors, it is important to identify genetic variants for each clinical characteristic of MetS.

Methods
We performed targeted next-generation sequencing (NGS) to identify genetic variants related to obesity, blood glucose, triacylglycerol (TG), and high-density lipoprotein (HDL)-cholesterol level, and hypertension in 48 subjects with MetS and in 48 healthy subjects.

Results
NGS analysis revealed that 26 of 48 subjects (54.2%) with MetS had putative non-synonymous variants related to the clinical features of MetS. Of the subjects with MetS, 8 (16.7%) had variants in 4 genes (COL6A2, FTO, SPARC, and MTHFR) related to central obesity, 17 (35.4%) had variants in 6 genes (APOB, SLC2A2, LPA, ABCG5, ABCG8, and GCKR) related to hyperglycemia, 3 (6.3%) had variants in 4 genes (APOA1, APOC2, APOA4, and LMF1) related to hypertriglyceridemia, 8 (16.7%) had variants in 4 genes (ABCA1, CETP, SCARB1, and LDLR) related to low HDL-cholesterolemia, and 5 (10.4%) had variants in ADD1 related to hypertension.

Conclusions
Our findings may contribute to broadening the genetic spectrum of risk variants related to the development of MetS.
Can formalisation of pastoral land tenure overcome its paradoxes? Reflections from East Africa
Authors: Robinson Lance , Flintan Fiona 
Published: August 2022

AbstractLegal frameworks for communal land rights in Ethiopia, Kenya, and Tanzania are now gaining momentum. Questions can be raised as to whether, how, and to what extent these frameworks take into account the disadvantages of formalising tenure and the complexities of pastoral resources. In this paper, we consider the impact of these challenges on the formalisation of communal ownership, beginning with an overview of how commons theory has influenced land governance policies and how it is applied to pastoral systems. We identify the main challenges that land policy interventions in East Africa face and ways in which the conceptual models of shared property rights embodied in current land tenure regimes are not well adapted to the socio-ecological characteristics of some rangeland landscapes. We argue that policy interventions capable of overcoming the paradox of pastoral tenure and strengthening tenure security while addressing herders’ needs for mobility and flexibility will often involve the progressive recognition of layers of sometimes overlapping rights, rather than attempts to subdivide landscapes into simple mosaics of discrete communal territories. This paper is based on an analysis of the legal frameworks for land tenure in the three countries and a review of the literature on pastoralism and land governance in the region.
Incidence of infant mortality and its predictors in East Africa using Gompertz gamma shared frailty model
Authors: Tesema Getayeneh Antehunegn , Seifu Beminate Lemma , Tessema Zemenu Tadesse , Worku Misganaw Gebrie , Teshale Achamyeleh Birhanu 
Published: August 2022

Abstract
Background
Globally, infant mortality is a major public health concern and a sensitive indicator of countries' socio-economic and health status. Despite the substantial reduction of under-five mortality in sub-Saharan African countries specifically in East Africa, the infant mortality rate remains highest and too far below to achieve the WHO target. As to our search of the literature is concerned, there is a dearth of evidence on the incidence and predictors of infant mortality in East Africa. Therefore, this study investigated the incidence of infant mortality and its predictors in East Africa.

Methods
The present study has utilized 138,803 weighted samples from Demographic and Health Surveys (DHSs) of 12 East African countries. Considering the hierarchical nature of DHS data shared frailty parametric survival models were fitted and compared based on deviance (-2LLR), AIC, and BIC. Gompertz gamma shared frailty model was the best-fitted model for the data since it had the lowest deviance, AIC, and BIC values. Variables with a p-value < 0.2 in the bi-variable analysis were considered for the multivariable analysis. In the multivariable Gompertz gamma shared analysis, the Adjusted Hazard Ratio (AHR) with 95% Confidence Interval (CI) was reported to declare the significant predictors of infant mortality.

Results
The infant mortality rate in East Africa was 41.41 per 1000 live births. Mothers aged 25–34 years, wanted birth, health facility delivery, 1–3 ANC visit, being 2nd- 4th birth order, 5th and above, the birth interval of 24–48 months, and birth interval of 49 months and above were significantly associated with lower risk of infant mortality. Whereas women who didn’t have formal education, women who didn't participate in making health care decisions making, being male children, cesarean delivery, small size at birth, and large size at birth were significantly associated with a higher risk of infant mortality.

Conclusion
Despite the substantial progress in improving maternal and child health, this study showed that infant mortality is still a major public health concern in East Africa. Maternal age, place of delivery, maternal education, birth size, sex of the child, mode of delivery, women's autonomy, birth order, birth interval, and ANC visit were found to be significant predictors of infant mortality. Therefore, public health interventions enhancing health facility delivery, ANC visit, maternal education, birth spacing, and empowering women are crucial for reducing the incidence of infant mortality in East Africa.
Global antimicrobial resistance: a system-wide comprehensive investigation using the Global One Health Index
Authors: Zhou Nan , Cheng Zile , Zhang Xiaoxi , Lv Chao , Guo Chaoyi , Liu Haodong , Dong Ke , Zhang Yan , Liu Chang , Chang Yung-Fu , Chen Sheng , Guo Xiaokui , Zhou Xiao-Nong , Li Min , Zhu Yongzhang 
Published: August 2022

Abstract
Background
Antimicrobial resistance (AMR) is one of the top ten global public health challenges. However, given the lack of a comprehensive assessment of worldwide AMR status, our objective is to develop a One Health-based system-wide evaluation tool on global AMR.

Methods
We have further developed the three-hierarchical Global One Health Index (GOHI)-AMR indicator scheme, which consists of five key indicators, 17 indicators, and 49 sub-indicators, by incorporating 146 countries’ data from diverse authoritative databases, including WHO's Global Antimicrobial Resistance and Use Surveillance System (GLASS) and the European CDC. We investigated the overall- or sub-rankings of GOHI-AMR at the international/regional/national levels for data preprocessing and score calculation utilizing the existing GOHI methodology. Additionally, a correlation analysis was conducted between the GOHI-AMR and other socioeconomic factors.

Results
The average GOHI-AMR score for 146 countries is 38.45. As expected, high-income countries (HICs) outperform the other three income groups on overall rankings and all five key indicators of GOHI-AMR, whereas low-income countries unexpectedly outperform upper-middle-income countries and lower-middle-income countries on the antibiotics-resistant key indicator (ARR) and ARR-subordinate indicators, including carbapenem-, β-lactam-, and quinolone resistance, and even HICs on aminoglycoside resistance. There were no significant differences among the four groups on the environmental-monitoring indicator (P > 0.05). GOHI-AMR was positively correlated with gross domestic product, life expectancy, and AMR-related publications, but negatively with natural growth rate and chronic respiratory disease. In contrast to Cyprus, the remarkably lower prevalence of "ESKAPE pathogens" in high-scoring Sweden and Denmark highlights Europe's huge gaps. China and Russia outperformed the other three BRICS countries on all key indicators, particularly India's ARR and Brazil's AMR laboratory network and coordination capacity. Furthermore, significant internal disparities in carbapenem-resistant Klebsiella pneumoniae (CRKP) and methicillin-resistant Staphylococcus aureus (MRSA) prevalence were observed between China and the USA, with MRSA prevalence both gradually declining, whereas CRKP prevalence has been declining in the USA but increasing in China, consistent with higher carbapenems-related indicator’ performance in USA.

Conclusions
GOHI-AMR is the most comprehensive tool currently available for the assessment of AMR status worldwide. We discovered unique features impacting AMR in each country and offered precise recommendations to improve the capacity to tackle AMR in low-ranking countries.

Graphical Abstract
Physio-pathological effects of N6-methyladenosine and its therapeutic implications in leukemia
Authors: Liu Wei-Wei , Wang Hao , Zhu Xiao-Yu 
Published: August 2022

AbstractN6-methyladenosine (m6A), the most prevalent epigenetic modification of RNA in mammals, has become a hot topic throughout recent years. m6A is involved with every links of the RNA fate, including RNA splicing, nuclear export, translation and stability. Due to the reversible and dynamic regulatory network composed of ‘writers’ (methylase), ‘erasers’ (demethylase) and ‘readers’ (m6A binding proteins), m6A has been deemed as an essential modulator in vast physiological and pathological processes. Previous studies have shown that aberrant expression and dysfunction of these regulators are implicated in diverse tumors, exemplified by hematological malignancies. However, we should hold a dialectic perspective towards the influence of m6A modification on leukemogenesis. Given that m6A itself is neither pro-oncogenic nor anti-oncogenic, whether the modifications promote hematological homeostasis or malignancies occurrence and progression is dependent on the specific targets it regulates. Ample evidence supports the role of m6A in maintaining normal hematopoiesis and leukemogenesis, thereby highlighting the therapeutic potential of intervention in m6A modification process for battling leukemia. In this review, we introduce the advances of m6A modification and summarize the biological functions of m6A in RNA metabolism. Then we discuss the significance of several well-studied m6A regulators in modulating normal and malignant hematopoiesis, with focus on the therapeutic potentials of targeting these regulators for battling hematopoietic malignancies.