bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors impacting antenatal care utilization: a systematic review of 37 fragile and conflict-affected situations
Authors: Alibhai Kameela Miriam , Ziegler Bianca R. , Meddings Louise , Batung Evans , Luginaah Isaac 
Published: June 2022

AbstractBackgroundIt is estimated that over 930 million people live in fragile and conflict-affected situations (FCAS) worldwide. These regions, characterized by violence, civil unrest, and war, are often governed by corrupt administrations who are unwilling to provide their citizens with basic human rights. Individuals living in FCAS face health inequities; however, women are disproportionally affected and face additional barriers to accessing sexual and reproductive services, including antenatal care (ANC). This systematic review aims to identify the factors that impact ANC usage in the 37 countries or regions classified as FCAS in 2020 by The World Bank.MethodsUsing the PRISMA guidelines, a systematic search of five databases (SCOPUS, Web of Science, PubMed, EMBASE, and CINAHL) was conducted. Results were limited to human studies, written in English, and published between January 2002 and January 2022. Studies that identified factors affecting utilization of ANC or maternal health services were included for review and critically appraised using the National Institute of Health’s Quality Assessment Tools. Findings were summarized using a narrative synthesis approach.ResultsThe database search yielded 26,527 studies. After title, abstract and full-text review, and exclusion of duplicate articles, 121 studies remained. Twenty-eight of the 37 FCAS were represented in the included studies. The studies highlighted that women in FCAS’ are still not meeting the World Health Organization’s 2002 recommendation of four ANC visits during pregnancy, a recommendation which has since been increased to eight visits. The most cited factors impacting ANC were socioeconomic status, education, and poor quality of ANC. Despite all studies being conducted in conflict-affected regions, only nine studies explicitly identified conflict as a direct barrier to accessing ANC.ConclusionThis review demonstrated that there is a paucity in the literature examining the direct and indirect impacts of conflict on ANC utilization. Specifically, research should be conducted in the nine FCAS that are not currently represented in the literature. To mitigate the barriers that prevent utilization of maternal health services identified in this review, policy makers, women utilizing ANC, and global organizations should attempt to collaborate to enact policy change at the local level.
Missing in action: the right to the highest attainable standard of mental health care
Authors: Song Yun Ju C. , Rosenberg Sebastian , Smith Belinda , Occhipinti Jo-An , Mendoza John , Freebairn Louise , Skinner Adam , Hickie Ian B. 
Published: June 2022

Abstract
Background
The right to the highest attainable standard of mental health remains a distant goal worldwide. The Report of the UN Special Rapporteur on the right of all people to enjoyment of the highest attainable standard of physical and mental health pleaded the urgent need for governments to act through appropriate laws and policies. We argue that Australia is in breach of international obligations, with inadequate access to mental health services, inconsistent mental health legislation across jurisdictions and ongoing structural (systematic) and individual discrimination.

Discussion
Inadequate access to mental health services is a worldwide phenomenon. Australia has committed to international law obligations under the Convention on the Rights of Persons with Disabilities (CRPD) to ‘promote, protect and ensure the full and equal enjoyment of all human rights and fundamental freedoms by all persons with disability, with respect to their inherent dignity’. This includes people with mental health impairment and this convention includes the right to ‘the highest attainable standard of mental health’. Under the Australian Constitution, ratification of this convention enables the national government to pass laws to implement the convention obligations, and such national laws would prevail over any inconsistent state (or territory) laws governing mental health service provision.

Summary
The authors argue that enabling positive rights through legislation and legally binding mental health service standards may facilitate enhanced accountability and enforcement of such rights. These steps may support critical key stakeholders to improve the standards of mental health service provision supported by the implementation of international obligations, thereby accelerating mental health system reform. Improved legislation would encourage better governance and the evolution of better services, making mental health care more accessible, without structural or individual discrimination, enabling all people to enjoy the highest attainable standard of health.
Foretinib can overcome common on-target resistance mutations after capmatinib/tepotinib treatment in NSCLCs with MET exon 14 skipping mutation
Authors: Fujino Toshio , Suda Kenichi , Koga Takamasa , Hamada Akira , Ohara Shuta , Chiba Masato , Shimoji Masaki , Takemoto Toshiki , Soh Junichi , Mitsudomi Tetsuya 
Published: June 2022

Abstract
Background
Capmatinib and tepotinib are guideline-recommended front-line treatments for non-small-cell lung cancer (NSCLC) patients with MET exon 14 skipping mutations (METex14). However, the emergence of acquired resistance to capmatinib/tepotinib is almost inevitable partially due to D1228X or Y1230X secondary mutations of the MET. In this study, we explored agents that are active against both D1228X and Y1230X MET to propose an ideal sequential treatment after capmatinib/tepotinib treatment failure in NSCLC patients with METex14.

Methods
The inhibitory effects of 300 drugs, including 33 MET-TKIs, were screened in Ba/F3 cells carrying METex14 plus MET D1228A/Y secondary mutations. The screen revealed four-candidate type II MET-TKIs (altiratinib, CEP-40783, foretinib and sitravatinib). Therefore, we performed further growth inhibitory assays using these four MET-TKIs plus cabozantinib and merestinib in Ba/F3 cells carrying MET D1228A/E/G/H/N/V/Y or Y1230C/D/H/N/S secondary mutations. We also performed analyses using Hs746t cell models carrying METex14 (with mutant allele amplification) with/without D1228X or Y1230X in vitro and in vivo to confirm the findings. Furthermore, molecular dynamics (MD) simulations were carried out to examine differences in binding between type II MET-TKIs.

Results
All 6 type II MET-TKIs were active against Y1230X secondary mutations. However, among these 6 agents, only foretinib showed potent activity against D1228X secondary mutations of the MET in the Ba/F3 cell and Hs746t in vitro model and Hs746t in vivo model, and CEP-40783 and altiratinib demonstrated some activity. MD analysis suggested that the long tail of foretinib plays an important role in binding D1228X MET through interaction with a residue at the solvent front (G1163). Tertiary G1163X mutations, together with L1195F/I and F1200I/L, occurred as acquired resistance mechanisms to the second-line treatment foretinib in Ba/F3 cell models.

Conclusions
The type II MET-TKI foretinib may be an appropriate second-line treatment for NSCLCs carrying METex14 after campatinib/tepotinib treatment failure by secondary mutations at residue D1228 or Y1230.
Essential role for STAT3/FOXM1/ATG7 signaling-dependent autophagy in resistance to Icotinib
Authors: Lyu Xin , Zeng Lizhong , Shi Jie , Ming Zongjuan , Li Wei , Liu Boxuan , Chen Yang , Yuan Bo , Sun Ruiying , Yuan Jingyan , Zhao Nannan , Yang Xia , Chen Guoan , Yang Shuanying 
Published: June 2022

Abstract
Background
The contribution of autophagy to cancer therapy resistance remains complex, mainly owing to the discrepancy of autophagy mechanisms in different therapy. However, the potential mechanisms of autophagy-mediated resistance to icotinib have yet to be elucidated.

Methods
The effect of autophagy in icotinib resistance was examined using a series of in vitro and in vivo assays. The results above were further verified in biopsy specimens of lung cancer patients before and after icotinib or gefitinib treatment.

Results
Icotinib increased ATG3, ATG5, and ATG7 expression, but without affecting Beclin-1, VPS34 and ATBG14 levels in icotinib-resistant lung cancer cells. Autophagy blockade by 3-MA or silencing Beclin-1 had no effects on resistance to icotinib. CQ effectively restored lung cancer cell sensitivity to icotinib in vitro and in vivo. Notably, aberrantly activated STAT3 and highly expressed FOXM1 were required for autophagy induced by icotinib, without the involvement of AMPK/mTOR pathway in this process. Alterations of STAT3 activity using genetic and/or pharmacological methods effectively affected FOXM1 and ATG7 levels increased by icotinib, with altering autophagy and icotinib-mediated apoptosis in resistant cells. Furthermore, silencing FOXM1 impaired up-regulated ATG7 induced by STAT3-CA and icotinib. STAT3/FOXM1 signalling blockade also reversed resistance to icotinib in vivo. Finally, we found a negative correlation between STAT3/FOXM1/ATG7 signalling activity and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) treatment efficacy in patients undergoing EGFR-TKIs treatment.

Conclusions
Our findings support that STAT3/FOXM1/ATG7 signalling-induced autophagy is a novel mechanism of resistance to icotinib, and provide insights into potential clinical values of ATG7-dependent autophagy in icotinib treatment.

Graphical abstract
The immune landscape of solid pediatric tumors
Authors: Sherif Shimaa , Roelands Jessica , Mifsud William , Ahmed Eiman I. , Raynaud Christophe M. , Rinchai Darawan , Sathappan Abbirami , Maaz Ata , Saleh Ayman , Ozer Erdener , Fakhro Khalid A. , Mifsud Borbala , Thorsson Vésteinn , Bedognetti Davide , Hendrickx Wouter R. L. 
Published: June 2022

AbstractBackgroundLarge immunogenomic analyses have demonstrated the prognostic role of the functional orientation of the tumor microenvironment in adult solid tumors, this variable has been poorly explored in the pediatric counterpart.MethodsWe performed a systematic analysis of public RNAseq data (TARGET) for five pediatric tumor types (408 patients): Wilms tumor (WLM), neuroblastoma (NBL), osteosarcoma (OS), clear cell sarcoma of the kidney (CCSK) and rhabdoid tumor of the kidney (RT). We assessed the performance of the Immunologic Constant of Rejection (ICR), which captures an active Th1/cytotoxic response. We also performed gene set enrichment analysis (ssGSEA) and clustered more than 100 well characterized immune traits to define immune subtypes and compared their outcome.ResultsA higher ICR score was associated with better survival in OS and high risk NBL without MYCN amplification but with poorer survival in WLM. Clustering of immune traits revealed the same five principal modules previously described in adult tumors (TCGA). These modules divided pediatric patients into six immune subtypes (S1-S6) with distinct survival outcomes. The S2 cluster showed the best overall survival, characterized by low enrichment of the wound healing signature, high Th1, and low Th2 infiltration, while the reverse was observed in S4. Upregulation of the WNT/Beta-catenin pathway was associated with unfavorable outcomes and decreased T-cell infiltration in OS.ConclusionsWe demonstrated that extracranial pediatric tumors could be classified according to their immune disposition, unveiling similarities with adults’ tumors. Immunological parameters might be explored to refine diagnostic and prognostic biomarkers and to identify potential immune-responsive tumors.
NCAPD3 enhances Warburg effect through c-myc and E2F1 and promotes the occurrence and progression of colorectal cancer
Authors: Jing Zuolei , Liu Qianmei , He Xinyuan , Jia Zhirong , Xu Zhizhong , Yang Bolin , Liu Ping 
Published: June 2022

Abstract
Background
NCAPD3 is one of the three non-SMC subunits of condensin II complex, which plays an important role in the chromosome condensation and segregation during mitosis. Notably, elevated levels of NCAPD3 are found in many somatic cancers. However, the clinical role, biological functions of NCAPD3 in cancers especially in colorectal cancer (CRC) and the underlying molecular mechanisms remain poorly elucidated.

Methods
Clinical CRC and adjacent normal tissues were used to confirm the expression of NCAPD3. The association of NCAPD3 expression with clinicopathological characteristics and patient outcomes were analyzed by using online database. In vivo subcutaneous tumor xenograft model, NCAPD3 gene knockout following azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced tumor mouse model, Co-IP, western blot, qRT-PCR, IHC, ChIP assays and cell functional assays were used to investigate the biological functions of NCAPD3 in CRC and the underlying molecular mechanisms.

Results
NCAPD3 was overexpressed in CRC tissues and positively correlated with poor prognosis of CRC patients. NCAPD3 knockout suppressed CRC development in AOM/DSS induced and xenograft mice models. Moreover, we found that NCAPD3 promoted aerobic glycolysis in CRC. Mechanistically, NCAPD3 up-regulated the level of c-Myc and interacted with c-Myc to recruit more c-Myc to the gene promoter of its downstream glycolytic regulators GLUT1, HK2, ENO1, PKM2 and LDHA, and finally enhanced cellular aerobic glycolysis. Also, NCAPD3 increased the level of E2F1 and interacted with E2F1 to recruit more E2F1 to the promoter regions of PDK1 and PDK3 genes, which resulted in the inhibition of PDH activity and TCA cycle.

Conclusions
Our data demonstrated that NCAPD3 promoted glucose metabolism reprogramming and enhanced Warburg effect in colorectal tumorigenesis and CRC progression. These findings reveal a novel mechanism underlying NCAPD3 mediated CRC cell growth and provide new targets for CRC treatment.
Culicoides species community composition and feeding preferences in two aquatic ecosystems in northern Spain
Authors: González Mikel A. , Goiri Fátima , Prosser Sean W. J. , Cevidanes Aitor , Hernández-Triana Luis M. , Barandika Jesús F. , Hebert Paul D. N. , García-Pérez Ana L. 
Published: June 2022

AbstractBackgroundAquatic ecosystems provide breeding sites for blood-sucking insects such asCulicoidesbiting midges (Diptera: Ceratopogonidae), but factors affecting their distribution and host choice are poorly understood. A study was undertaken at two nature reserves in northern Spain to examine the abundance, species composition, population dynamics and feeding patterns of biting midges between 2018 and 2019.MethodsCulicoideswere captured by light suction traps baited with CO2and by sweep netting vegetation. Blood meals and species identification of blood-fed specimens were determined using cytochromecoxidase I subunit (COI) DNA barcoding. Multivariate generalized linear models were used to evaluate the associations between the abundance ofCulicoides, the species richness and other parameters.ResultsThe 4973 identified specimens comprised 28 species ofCulicoides. These included two species reported for the first time in northern Spain, thus raising to 54 the number ofCulicoidesspecies described in the region. Specimens of all 28 species and 99.6% of the total specimens collected were caught in suction traps, while sweep netting vegetation revealed just 11 species and 0.4% of the total specimens. Midge abundance peaked in June/early July, with five species comprising > 80% of the captures:Culicoides alazanicus(24.9%),Culicoides griseidorsum(20.3%),Culicoides poperinghensis(16.2%),Culicoides kibunensis(10.7%) andCulicoides clastrieri(9.6%). DNA barcode analysis of blood meals from eightCulicoidesspecies revealed that they fed on 17 vertebrate species (3 mammals and 14 birds). Species in the subgenusAvaritiawere primarily ornithophilic, except forC. griseidorsumandC. poperinghensis.Host DNA from blood meals was successfully amplified from 75% of blood-fed females. A pictorial blood meal digestion scale is provided to accurately assess the blood-fed status of femaleCulicoides.ConclusionsThe large number of different blood meal sources identified in the midges captured in this study signals the likely importance of wild birds and mammals (e.g. red deer and wild boar) as reservoir/amplifying hosts for pathogens. Available hosts are more exposed to being bitten by biting midge populations in aquatic ecosystems in late spring and early summer.
The 2021–2022 position of Brazilian Diabetes Society on diabetic kidney disease (DKD) management: an evidence-based guideline to clinical practice. Screening and treatment of hyperglycemia, arterial hypertension, and dyslipidemia in the patient with DKD
Authors: de Sá João Roberto , Rangel Erika Bevilaqua , Canani Luis Henrique , Bauer Andrea Carla , Escott Gustavo Monteiro , Zelmanovitz Themis , Bertoluci Marcello Casaccia , Silveiro Sandra Pinho 
Published: June 2022

Abstract
Background
Diabetic kidney disease is the leading cause of end-stage renal disease and is associated with increased morbidity and mortality. This review is an authorized literal translation of part of the Brazilian Diabetes Society (SBD) Guidelines 2021–2022. This evidence-based guideline provides guidance on the correct management of Diabetic Kidney Disease (DKD) in clinical practice.

Methods
The methodology was published elsewhere in previous SBD guidelines and was approved by the internal institutional Steering Committee for publication. Briefly, the Brazilian Diabetes Society indicated 14 experts to constitute the Central Committee, designed to regulate methodology, review the manuscripts, and make judgments on degrees of recommendations and levels of evidence. SBD Renal Disease Department drafted the manuscript selecting key clinical questions to make a narrative review using MEDLINE via PubMed, with the best evidence available including high-quality clinical trials, metanalysis, and large observational studies related to DKD diagnosis and treatment, by using the MeSH terms [diabetes], [type 2 diabetes], [type 1 diabetes] and [chronic kidney disease].

Results
The extensive review of the literature made by the 14 members of the Central Committee defined 24 recommendations. Three levels of evidence were considered: A. Data from more than 1 randomized clinical trial or 1 metanalysis of randomized clinical trials with low heterogeneity (I2 < 40%). B. Data from metanalysis, including large observational studies, a single randomized clinical trial, or a pre-specified subgroup analysis. C: Data from small or non-randomized studies, exploratory analyses, or consensus of expert opinion. The degree of recommendation was obtained based on a poll sent to the panelists, using the following criteria: Grade I: when more than 90% of agreement; Grade IIa 75–89% of agreement; IIb 50–74% of agreement, and III, when most of the panelist recommends against a defined treatment.

Conclusions
To prevent or at least postpone the advanced stages of DKD with the associated cardiovascular complications, intensive glycemic and blood pressure control are required, as well as the use of renin–angiotensin–aldosterone system blocker agents such as ARB, ACEI, and MRA. Recently, SGLT2 inhibitors and GLP1 receptor agonists have been added to the therapeutic arsenal, with well-proven benefits regarding kidney protection and patients’ survival.
Ion content, antioxidant enzyme activity and transcriptional response under salt stress and recovery condition in the halophyte grass Aeluropus littoralis
Authors: Hashemipetroudi Seyyed Hamidreza , Ahmadian Gholamreza , Fatemi Farzaneh , Nematzadeh Ghorbanali , Yamchi Ahad , Kuhlmann Markus 
Published: June 2022

Abstract
Objective
In contrast to glycophytes, halophyte plants have evolved unique morphological and physiological mechanisms to deal with abiotic stress. This study presents the physiological responses of Aeluropus littoralis, a halophyte grass, to salt stress and recovery conditions on the molecular level.

Results
Elemental analysis showed that Na+ concentration increased in the analyzed tissue during salt stress application, and declined at recovery condition. With the exception of root tissue, comparable trends of K+, Ca2+, and Mg2+ concentrations were observed (decreased during salt stress, increased during recovery). Salinity led to an increase in total chlorophyll (Chl), Chl a, and carotenoids content, while Chl b content decreased. The level of the proline amino acid associated with drought and salt stress was increased. Here APX, POD, and SOD activity were strongly detectable in roots and reduced later under recovery conditions. RT-qPCR revealed up-regulation of antioxidant genes at S1 and S3 in the root but down-regulation in recovery conditions. This study found a significant halophyte index for understanding the processes of salinity tolerance in A. littoralis. These findings may provide insight into the role of antioxidant enzymes during salt stress and the mechanism underlying the plant's response to stress.
Clarifying SABA overuse: Translating Canadian Thoracic Society guidelines into clinical practice
Authors: Ellis Anne K. , Foran Vanessa , Kaplan Alan , Mitchell Patrick D. 
Published: June 2022

AbstractPatients with asthma frequently over rely on short-acting beta-agonists (SABA) to treat acute symptoms. This can adversely impact quality of life and increase the risk of exacerbations. SABA overuse is also associated with an increased risk of mortality. In their 2021 update on the diagnosis and management of mild asthma, the Canadian Thoracic Society (CTS) newly recommended that a combination inhaled corticosteroid (ICS) and long-acting beta-agonist, specifically budesonide/formoterol, may be used as-needed (PRN) as an alternative reliever to SABA. The CTS developed an algorithm as a guide for deciding for whom PRN budesonide/formoterol versus PRN SABA is appropriate as a reliever. While the CTS algorithm provides necessary and precise guidance, the somewhat complicated requirements for determining control and exacerbation risk may still end up leaving some patients at-risk of SABA overreliance. This communication simplifies the reliever decision algorithm developed by the CTS for application in daily practice. A 30-s evaluation of 2 simple questions related to reliever use can usually accurately assess if a patient’s asthma is controlled: How many SABA canisters do you use a year AND how many times do you use SABA a week? If the patient indicates use of > 2 SABA canisters per year or > 2 administrations of SABA per week for any reason, the patient does not have controlled asthma and PRN SABA is not an appropriate treatment regimen. Similarly, for patients using PRN ICS/formoterol, more than 2 administrations per week indicates a clinical review and reevaluation of their management, including augmentation. An education process is essential to inform patients, caregivers, and healthcare providers that overuse of any reliever is not acceptable and is potentially harmful.