bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypoxia favors chemoresistance in T-ALL through an HIF1α-mediated mTORC1 inhibition loop
Authors: Fahy Lucine , Calvo Julien , Chabi Sara , Renou Laurent , Le Maout Charly , Poglio Sandrine , Leblanc Thierry , Petit Arnaud , Baruchel André , Ballerini Paola , Naguibneva Irina , Haddad Rima , Arcangeli Marie-Laure , Mazurier Frederic , Pflumio Francoise , Uzan Benjamin 
Published: January 2021

Abstract
Resistance to chemotherapy, a major therapeutic challenge in the treatment of T-cell acute lymphoblastic leukemia (T-ALL), can be driven by interactions between leukemic cells and the microenvironment that promote survival of leukemic cells. The bone marrow, an important leukemia niche, has low oxygen partial pressures that highly participate in the regulation of normal hematopoiesis. Here we show that hypoxia inhibits T-ALL cell growth by slowing down cell cycle progression, decreasing mitochondria activity, and increasing glycolysis, making them less sensitive to antileukemic drugs and preserving their ability to initiate leukemia after treatment. Activation of the mammalian target of rapamycin (mTOR) was diminished in hypoxic leukemic cells, and treatment of T-ALL with the mTOR inhibitor rapamycin in normoxia mimicked the hypoxia effects, namely decreased cell growth and increased quiescence and drug resistance. Knocking down (KD) hypoxia-induced factor 1α (HIF-1α), a key regulator of the cellular response to hypoxia, antagonized the effects observed in hypoxic T-ALL and restored chemosensitivity. HIF-1α KD also restored mTOR activation in low O2 concentrations, and inhibiting mTOR in HIF1α KD T-ALL protected leukemic cells from chemotherapy. Thus, hypoxic niches play a protective role of T-ALL during treatments. Inhibition of HIF-1α and activation of the mTORC1 pathway may help suppress the drug resistance of T-ALL in hypoxic niches.
Cyclicality of labour market search: a new big data approach
Authors: Hutter Christian 
Published: January 2021

AbstractThis paper exploits big data on online activity from the job exchange of the German Federal Employment Agency and its internal placement-software to generate measures for search activity of employers and job seekers and—as a novel feature—for placement activity of employment agencies. In addition, the average search perimeter in the job seekers’ search profiles can be measured. The data are used to estimate the behaviour of the search and placement activities during the business and labour market cycle and their seasonal patterns. The results show that the search activities of firms and employment agencies are procyclical. By contrast, job seekers’ search intensity shows a countercyclical pattern, at least before the COVID-19 crisis.
Implementing interventions to reduce antibiotic use: a qualitative study in high-prescribing practices
Authors:   on behalf of the STEP-UP study team, Borek Aleksandra J. , Campbell Anne , Dent Elle , Butler Christopher C. , Holmes Alison , Moore Michael , Walker A. Sarah , McLeod Monsey , Tonkin-Crine Sarah 
Published: January 2021

Abstract
Background
Trials have shown that delayed antibiotic prescriptions (DPs) and point-of-care C-Reactive Protein testing (POC-CRPT) are effective in reducing antibiotic use in general practice, but these were not typically implemented in high-prescribing practices. We aimed to explore views of professionals from high-prescribing practices about uptake and implementation of DPs and POC-CRPT to reduce antibiotic use.

Methods
This was a qualitative focus group study in English general practices. The highest antibiotic prescribing practices in the West Midlands were invited to participate. Clinical and non-clinical professionals attended focus groups co-facilitated by two researchers. Focus groups were audio-recorded, transcribed verbatim and analysed thematically.

Results
Nine practices (50 professionals) participated. Four main themes were identified. Compatibility of strategies with clinical roles and experience – participants viewed the strategies as having limited value as ‘clinical tools’, perceiving them as useful only in ‘rare’ instances of clinical uncertainty and/or for those less experienced. Strategies as ‘social tools’ – participants perceived the strategies as helpful for negotiating treatment decisions and educating patients, particularly those expecting antibiotics. Ambiguities – participants perceived ambiguities around when they should be used, and about their impact on antibiotic use. Influence of context – various other situational and practical issues were raised with implementing the strategies.

Conclusions
High-prescribing practices do not view DPs and POC-CRPT as sufficiently useful ‘clinical tools’ in a way which corresponds to the current policy approach advocating their use to reduce clinical uncertainty and improve antimicrobial stewardship. Instead, policy attention should focus on how these strategies may instead be used as ‘social tools’ to reduce unnecessary antibiotic use. Attention should also focus on the many ambiguities (concerns and questions) about, and contextual barriers to, using these strategies that need addressing to support wider and more consistent implementation.
Multiple drug resistance of Campylobacter jejuni and Shigella isolated from diarrhoeic children at Kapsabet County referral hospital, Kenya
Authors: Zachariah Ongwae H. , Lizzy Mwamburi A. , Rose Kakai , Angela Mutuku M. 
Published: January 2021

Abstract
Background
Diarrhoea is a common cause of mortality and morbidity in children under five years old. In Kenya, it has a 21% case fatality with Enteropathogenic E. coli, Campylobacter jejuni, Shigella spp. and Salmonella spp. accounting for 50–60% of the cases. Sulphonamides, tetracycline, ampicillin and trimethoprim/sulfamethoxazole are typically used in the treatment of diarrhoeal diseases but have become ineffective in the face of emerging antimicrobial resistance. The objective of this study was to evaluate the prevalence and antimicrobial susceptibility of Campylobacter jejuni and Shigella species in children under five years of age presenting with diarrhoea at Kapsabet County Referral Hospital in Kenya.

Methods
Faecal samples were collected from 139 children admitted with diarrhoea. Each sample was examined macroscopically for colour, texture, and presence of extraneous material. The samples were then cultured for bacterial growth. Observed bacterial growth was isolated and identified by a series of biochemical tests. Resistance patterns were also evaluated using the Kirby – Bauer Disk diffusion method. The chi – square test and Pearson Correlation Coefficient were used to establish statistical significance.

Results
Approximately 33.1% of the total faecal samples tested were positive for enteric pathogens. Shigella spp. demonstrated resistance to erythromycin (91.7%), doxycyclin (83.3%), ampicillin (82.1%), cotrimoxazole (73.1%), minocycline (66.7%) and cefuroxime (54.2%). Campylobacter jejuni also exhibited resistance to erythromycin (87.5%), doxycyclin (75%), ampicillin (73.7%), cotrimoxazole (73.3%) and minocycline (68.8%).

Conclusions
The resistance patterns of Shigella spp. and Campylobacter jejuni reported in this study necessitates the need for a comprehensive multiregional investigation to evaluate the geographical prevalence and antimicrobial resistance distributions of these microorganisms. These findings also support the need for the discovery and development of effective therapeutic alternatives.

Trial registration
Retrospectively registered. Certificate No. 00762
The knowledge of danger signs of obstetric complications among women in rural India: evaluating an integrated microfinance and health literacy program
Authors: Ahmad Danish , Mohanty Itismita , Hazra Avishek , Niyonsenga Theo 
Published: January 2021

Abstract
Background
Maternal mortality can be prevented in low-income settings through early health care seeking during maternity complications. While health system reforms in India prioritised institutional deliveries, inadequate antenatal and postnatal services limit the knowledge of danger signs of obstetric complications to women, which delays the recognition of complications and seeking appropriate health care. Recently, a novel rapidly scalable community-based program combining maternal health literacy delivery through microfinance-based women-only self-help groups (SHG) was implemented in rural India. This study evaluates the impact of the integrated microfinance and health literacy (IMFHL) program on the knowledge of maternal danger signs in marginalised women from one of India’s most populated and poorer states - Uttar Pradesh. Additionally, the study evaluates the presence of a diffusion effect of the knowledge of maternal danger signs from SHG members receiving health literacy to non-members in program villages.

Methods
Secondary data from the IMFHL program comprising 17,232 women from SHG and non-member households in rural Uttar Pradesh was included. Multivariate logistic regression models were used to identify the program’s effects on the knowledge of maternal danger signs adjusting for a comprehensive range of confounders at the individual, household, and community level.

Results
SHG member women receiving health literacy were 27% more likely to know all danger signs as compared with SHG members only. Moreover, the results showed that the SHG network facilitates diffusion of knowledge of maternal danger signs from SHG members receiving health literacy to non-members in program villages. The study found that the magnitude of the program impact on outcome remained stable even after controlling for other confounding effects suggesting that the health message delivered through the program reaches all women uniformly irrespective of their socioeconomic and health system characteristics.

Conclusions
The findings can guide community health programs and policy that seek to impact maternal health outcomes in low resource settings by demonstrating the differential impact of SHG alone and SHG plus health literacy on maternal danger sign knowledge.
Mothers’ experiences of parenting and everyday life of children born at 23 weeks of gestation – a qualitative descriptive study
Authors: Väliaho Anniina , Lehtonen Liisa , Axelin Anna , Korja Riikka 
Published: January 2021

Abstract
Background
Surviving children born at 23 gestational weeks are a growing population. As many of these children face developmental challenges during childhood and adolescence, more knowledge is needed about the everyday life of this group. The parental perspective is important, as developmental problems often pose a challenge for the parents. The aim of this qualitative study was to explore mothers’ experiences of parenting children born at 23 gestational weeks and of the children’s everyday lives.

Methods
This was a qualitative descriptive study conducted with mothers of children born at 23 weeks of gestation. These purposively sampled eight mothers were interviewed using a semi-structured interview. Thematic analysis was used to analyse the interviews.

Results
Seven themes were formed on the basis of the interview data and they are presented in three dimensions: 1) the child seen from maternal perspective included themes ‘emphasizing strengths in the midst of challenges’, ‘relations with peers and siblings’, and ‘emotional well-being and active life’; 2) the parenting experience included themes ‘intensive mothering’ and ‘gratitude’; 3) the support included themes ‘support from the social network’ and ‘support from society’.

Conclusions
The mothers described how the lives of their children were active and rich. The mothers were dedicated to motherhood and they also expressed feelings of gratitude. Mothers received support from social networks and from society. This qualitative study provided an important complementary perspective to the discussion on extremely premature children’s quality of life. It also highlighted the importance of parental perspectives in assessing neonatal care and its outcomes.
Portal vein thrombosis and food protein-induced allergic proctocolitis in a premature newborn with hypereosinophilia: a case report
Authors: Moon Cheong-Jun , Kwon Tae Hee , Lee Hyun-Seung 
Published: January 2021

Abstract
Background
Peripheral blood eosinophilia is identified in numerous medical conditions associated with allergic, infectious, and inflammatory processes mostly as reactive eosinophilia with or without tissue eosinophilia. In hospitalized neonates, eosinophilia is common with an inverse relationship with gestational age and occurs solely as mild eosinophilia in the majority of cases. In the literature, eosinophilia has been proposed as a possible risk factor for venous thromboembolism. However, few reports are found on thromboembolic events including portal vein thrombosis (PVT) associated with eosinophilia in the newborn period.
Neonates, particularly preterm infants, are vulnerable to thrombosis due to the immature and developing hemostatic system with little reserve capacity, which occurs as catheter-related thrombosis in most cases.

Case presentation
A male newborn at 34+ 5 weeks’ gestation presented with a left portal venous thrombus and hematochezia after initial cow’s milk feeding in the setting of blood hypereosinophilia for a prolonged period of time without central venous catheterization. The infant was diagnosed with PVT and food protein-induced allergic proctocolitis (FPIAP) and showed complete resolution of the conditions with expectant management with food avoidance, including the normalized eosinophil count.

Conclusions
Our experience suggests that in the setting of hypereosinophilia with a prolonged duration in premature neonates, FPIAP should be suspected in case of hematochezia in otherwise healthy infants, and considering the increased thrombotic risk by the hypereosinophilia and premature newborn status, evaluation for neonatal thrombosis may be needed, including PVT with the potential risk for the more serious, but uncommon, late complications encompassing portal hypertension.
Considerations about the implementation of an autism screening program in Iran from the viewpoints of professionals and parents: a qualitative study
Authors: Shahrokhi Hassan , Ghiasi Akbar , Gholipour Kamal , Fanid Leila Mehdizadeh , Shamekhi Hamid Reza , Iezadi Shabnam 
Published: January 2021

Abstract
Background
The aims of this study were to explore to explore the viewpoints of parents of children with Autism Spectrum Disorders (ASD) and professionals regarding the implementation of screening programs for ASD, to explore the challenges of the implementation of a universal screening program for ASD in Iran from their viewpoints, and, to explore their recommendations to overcome the potential challenges.

Method
This qualitative study was conducted using an inductive content analysis, between June 2018 and December 2018, in East-Azerbaijan province of Iran. Data was collected through in-depth interviews and focus group discussions. The participants were purposively selected among two groups: representatives of health system and representatives of children with ASD. A sample of 32 parents and 30 professionals were recruited in this study.

Results
Totally, 9 main themes and 23 sub-themes were extracted in three main areas including: viewpoints of the participants about universal screening for ASD, challenges in implementation of the universal screening program, and participants’ recommendations about how to overcome the potential challenges. Main challenges in implementation of the universal screening program included: shortages of ASD screening tools, weakness of the health system, lack of coordination among the ASD service providers, and social and ethical issues.

Conclusion
The parents and the professionals had different viewpoints about the implementation of ASD universal screening program in Iran. According to the professionals, there is not enough rational to implement ASD screening program for all children. However, the parents believed that universal screening program is inevitable, and it should be implemented in primary health centers during the early child-care visits. The results of this study open up unspoken issues that could help in initiating the screening program not only in Iran but also in other low- and middle-income countries as well.
Safe standard remnant liver volume after hepatectomy in HCC patients in different stages of hepatic fibrosis
Authors: Zhang Zhiming , Ouyang Gaoxiong , Wang Peng , Ren Yuan , Liu Yukai , Chen Jun , Zhang Yumei , Liu Jianyong , Li Lequn 
Published: January 2021

Abstract
Background
To determine the standard remnant liver volume (SRLV) threshold to avoid postoperative hepatic insufficiency inpatients in different stages of hepatic fibrosis who undergo right hemi-hepatectomy.

Methods
Data for 85 patients at our single medical center were analysed prospectively to examine whether the following factors differed significantly between those who experienced postoperative hepatic insufficiency and those who did not: height, prothrombin time, remnant liver volume, SRLV or hepatic fibrosis stage.

Results
Logistic regression showed SRLV and hepatic fibrosis stage to be independent risk factors for postoperative hepatic insufficiency. The threshold SRLV for predicting insufficiency was 203.2 ml/m2 across all patients [area under receiver operating characteristic curve (AUC) 0.778, sensitivity 66.67%, specificity 83.64%, p<0.0001), 193.8 ml/m2 for patients with severe hepatic fibrosis (AUC 0.938, sensitivity 91.30%, specificity 85.71%, p<0.0001), and 224.3 ml/m2 for patients with cirrhosis (AUC 0.888, sensitivity 100%, specificity 64.29%, p<0.0001).

Conclusions
Right hemi-hepatectomy may be safer in Chinese patients when the standard remnant liver volume is more than 203.2 ml/m2 in the absence of hepatic fibrosis or cirrhosis, 193.8 ml/m2 in the presence of severe hepatic fibrosis or 224.3 ml/m2 in the presence of cirrhosis.
The use of an O-arm in endonasal endoscopic operations of the skull base
Authors: Novák Vlastimil , Hrabálek Lumír , Valošek Jan , Jablonský Jakub , Hoza Jiří , Korčáková Ivona , Hampl Martin , Stejskal Přemysl , Hučko Csaba 
Published: January 2021

Abstract
Background
Endoscopic endonasal transsphenoidal approaches are broadly used nowadays for a vast spectrum of pathologies sited in the anterior and middle cranial fossa. The usage of neuronavigation systems (neuronavigation) in these surgeries is crucial for improving orientations deeply inside the skull and increasing patient safety.

Methods
The aim of this study was to assess the use of optical neuronavigation, together with an intraoperative O-arm O2 imaging system, in a group of patients with hypophyseal adenoma that underwent a transnasal transsphenoidal surgery, and correlate the accuracy and its deviation during the navigational process against the use of conventional neuronavigation that uses preoperative MRI and CT scans. The overall group consisted of six patients, between 39 and 78 years old, with a diagnosis of hypophyseal adenoma. Patients were treated with an endoscopic transsphenoidal technique and all of them underwent preoperative MRI and CT scans of the brain. These images were used in the neuronavigation system StealthStation S7® during the surgery, where we defined two bony anatomical landmarks, such as a vomer or the origin of an intrasphenoidal septum, in each operated patient. The tip of the navigational instrument, under endoscopic control, pointed to these landmarks and the distance between the tip and the bony structure was measured on the neuronavigation system. Afterwards, intraoperative 3D x-ray imaging was performed via the mobile system O-arm O2® system with automatic transfer into the navigational system. Under endoscopic guidance, we localized the identical bony anatomical landmarks used in the previous measurement and re-measured the distance between the tip and bony landmark in images acquired by the O-arm. The results of both measurements were statistically compared.

Results
The mean error of accuracy during conventional neuronavigation with usage of preoperative CT and MRI scans was 2.65 mm. During the neuronavigation, with utilization of intraoperative 3D O-arm images, the mean error of accuracy 0 mm. These mean errors of accuracy (both measurement methods were compared by nonparametric Wilcoxon test) had a statistically significant difference (p = 0.043).

Conclusions
Based on this preliminary clinical study, we conclude that the O-arm is capable of providing intraoperative x-ray 3D images in sufficient spatial resolution in a clinically feasible acquisition. The mean error of accuracy during intraoperative navigation, based on 3D O-arm scans at the skull base, is significantly lower compared to the usage of navigation using conventional presurgical CT and MRI images. This suggests the suitability of this method for utilization during endoscopic endonasal skull base approaches.
Site-specific metastases of gallbladder adenocarcinoma and their prognostic value for survival: a SEER-based study
Authors: Yang Yingnan , Tu Zhuolong , Ye Chentao , Cai Huajie , Yang Shouzhang , Chen Xuehai , Tu Jinfu 
Published: January 2021

Abstract
Background
Gallbladder cancer is a rare but highly malignant cancer, which often progresses to a metastatic stage when diagnosed because of its asymptomatic manifestation. In this study, we intended to analyze the prognostic value of metastatic gallbladder adenocarcinoma (GBA) with site-specific metastases.

Methods
Using the Surveillance, Epidemiology, and End Results (SEER) database, GBA patients diagnosed with metastases between 2010 and 2016 were selected to identify the prognosis according to the isolated metastatic sites, including liver, lung, bone, brain and distant lymph nodes (DL). Kaplan–Meier methods were used for survival comparisons and multivariable Cox regression models were constructed to find out independent factors that associated with survival.

Results
Data from 1526 eligible patients were extracted from the SEER database. Among the patients, 788 (51.6%) had isolated liver metastases, 80 (5.2%) had isolated distant nodal involvement, 45 (2.9%) had isolated lung metastases, 21 (1.4%) had isolated bone metastases, 2 (0.1%) had isolated brain metastases and 590 (38.7%) had multiple metastases. No significant survival difference was shown between patients with single or multisite metastases (P > 0.05). Patients with isolated lung or DL metastases had significant better survival outcomes than those with isolated bone metastases (P < 0.05). Multivariate analysis showed that performing surgery at primary site, receiving chemotherapy were associated with better OS and CSS for patients with isolated liver or DL metastases.

Conclusions
The study showed that different metastatic sites affect survival outcomes in metastatic GBA patients. Highly selected subset of patients with liver or DL metastases might benefit from surgery at primary site.