bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inclusion of diabetic retinopathy screening strategies in national-level diabetes care planning in low- and middle-income countries: a scoping review
Authors: Curran Katie , Piyasena Prabhath , Congdon Nathan , Duke Lisa , Malanda Belma , Peto Tunde 
Published: January 2023

Abstract
Background
Diabetes is a major public health concern, with approximately 80% of the burden falling on low- and middle-income countries (LMICs). Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, and early detection through diabetic eye screening programmes is essential to prevent visual impairment and blindness. Careful planning at a national level is crucial for effective implementation of such programmes.

Methods
A scoping review was conducted, and the protocol was published previously to explain the methods in detail. Data were collected from databases and searches, including grey literature. Furthermore, consultations were conducted with key informants from LMICs.

Results
Lower-middle-income countries (29/50, 58%) and upper-middle-income countries (27/59, 45.8%) are making more progress than low-income countries (4/29, 13.8%) in terms of DR policy planning. However, no identified data for published policies have actually implemented national DR policies. Compared to low-income and lower-middle-income countries, upper-middle-income countries are making the most progress in implementing national diabetic eye screening programmes; however, their progress is still slow, with only 5/59 (8.5%) having such programmes.

Conclusion
There are significant gaps in the literature, with no data reported for 78/138 (56.5%) LMICs. Further research is clearly needed to support and document DR policy development in LMICs.
Extracellular vesicles from mesenchymal stem cells reduce neuroinflammation in hippocampus and restore cognitive function in hyperammonemic rats
Authors: Izquierdo-Altarejos Paula , Cabrera-Pastor Andrea , Martínez-García Mar , Sánchez-Huertas Carlos , Hernández Alberto , Moreno-Manzano Victoria , Felipo Vicente 
Published: January 2023

AbstractChronic hyperammonemia, a main contributor to hepatic encephalopathy (HE), leads to neuroinflammation which alters neurotransmission leading to cognitive impairment. There are no specific treatments for the neurological alterations in HE. Extracellular vesicles (EVs) from mesenchymal stem cells (MSCs) reduce neuroinflammation in some pathological conditions. The aims were to assess if treatment of hyperammonemic rats with EVs from MSCs restores cognitive function and analyze the underlying mechanisms. EVs injected in vivo reach the hippocampus and restore performance of hyperammonemic rats in object location, object recognition, short-term memory in the Y-maze and reference memory in the radial maze. Hyperammonemic rats show reduced TGFβ levels and membrane expression of TGFβ receptors in hippocampus. This leads to microglia activation and reduced Smad7–IkB pathway, which induces NF-κB nuclear translocation in neurons, increasing IL-1β which alters AMPA and NMDA receptors membrane expression, leading to cognitive impairment. These effects are reversed by TGFβ in the EVs from MSCs, which activates TGFβ receptors, reducing microglia activation and NF-κB nuclear translocation in neurons by normalizing the Smad7–IkB pathway. This normalizes IL-1β, AMPA and NMDA receptors membrane expression and, therefore, cognitive function. EVs from MSCs may be useful to improve cognitive function in patients with hyperammonemia and minimal HE.
Premature ovarian insufficiency in female adolescent and young adult survivors of non-gynecological cancers: a population-based cohort study
Authors: Flatt Sydney B. , Baillargeon Amanda , McClintock Chad , Pudwell Jessica , Velez Maria P. 
Published: January 2023

Abstract
Background
The risk of premature ovarian insufficiency (POI) is increased in adolescent and young adult (AYA) cancer survivors, with the prevalence depending on cancer diagnosis, treatment, and patient factors. Prior studies are limited by sample size and type of cancer included. The objective of this study was to assess the risk of POI in female AYA survivors of non-gynecologic cancers, using a population-based approach.

Methods
This population-based retrospective cohort study comprises 21,666 females, 15–39 years old, diagnosed with a single non-gynecologic cancer in Ontario, Canada from 1995 to 2015.
Through health administrative data linkage, participants were followed until their 40th birthday, December 31, 2018, bilateral oophorectomy, loss of health insurance eligibility or death. Each cancer survivor was matched to 5 females who were not diagnosed with cancer (unexposed, n = 108,330). Women with bilateral oophorectomy or a prior menopause diagnosis were excluded. POI was identified through use of the ICD-9 code for menopause (ICD9-627). Modified Poisson regression models were used to calculate the adjusted relative risk (aRR) of POI for AYA cancer survivors compared to unexposed individuals, adjusted for income, parity, age, and immigration status.

Results
The occurrence of POI was higher in survivors of AYA cancer versus unexposed patients (5.4% vs. 2.2%). Survivors of AYA cancer had an increased risk of POI relative to unexposed patients (aRR 2.49; 95% CI 2.32–2.67). Risk varied by type of cancer: breast (4.32; 3.84–4.86), non-Hodgkin’s lymphoma (3.77; 2.88–4.94), Hodgkin’s lymphoma (2.37; 1.91–2.96), leukemia (14.64; 10.50–20.42), thyroid (1.26; 1.09–1.46) and melanoma (1.04; 0.82–1.32). Risk varied by age at time of cancer diagnosis, with a higher risk among females diagnosed at age 30–39 years (3.07; 2.80–3.35) than aged 15–29 years (1.75; 1.55–1.98).

Conclusions
AYA survivors of non-gynecologic cancers are at an increased risk of POI, particularly survivors of lymphomas, leukemia, breast, and thyroid cancer. The risk of POI is increased for those diagnosed with cancer at an older age. These results should inform reproductive counseling of female AYAs diagnosed with cancer.
Mediation of PKM2-dependent glycolytic and non-glycolytic pathways by ENO2 in head and neck cancer development
Authors: Gao Lixia , Yang Fan , Tang Dianyong , Xu Zhigang , Tang Yan , Yang Donglin , Sun Deping , Chen Zhongzhu , Teng Yong 
Published: January 2023

Abstract
Background
Enolase 2 (ENO2) is a crucial glycolytic enzyme in cancer metabolic process and acts as a “moonlighting” protein to play various functions in diverse cellular processes unrelated to glycolysis. ENO2 is highly expressed in head and neck squamous cell carcinoma (HNSCC) tissues relative to normal tissues; however, its impact and underlying regulatory mechanisms in HNSCC malignancy remain unclear.

Methods
Molecular alterations were examined by bioinformatics, qRT-PCR, western blotting, immunofluorescence, immunohistochemistry, immunoprecipitation, and ChIP-PCR assays. Metabolic changes were assessed by intracellular levels of ATP and glucose. Animal study was used to evaluate the therapeutic efficacy of the ENO inhibitor.

Results
ENO2 is required for HNSCC cell proliferation and glycolysis, which, surprisingly, is partially achieved by controlling PKM2 protein stability and its nuclear translocation. Mechanistically, loss of ENO2 expression promotes PKM2 protein degradation via the ubiquitin-proteasome pathway and prevents the switch of cytoplasmic PKM2 to the nucleus by inactivating AKT signaling, leading to a blockade in PKM2-mediated glycolytic flux and CCND1-associated cell cycle progression. In addition, treatment with the ENO inhibitor AP-III-a4 significantly induces HNSCC remission in a preclinical mouse model.

Conclusion
Our work elucidates the signaling basis underlying ENO2-dependent HNSCC development, providing evidence to establish a novel ENO2-targeted therapy for treating HNSCC.
PCSK9 facilitates melanoma pathogenesis via a network regulating tumor immunity
Authors: Gu Yan , Lin Xiaozeng , Dong Ying , Wood Geoffrey , Seidah Nabil G. , Werstuck Geoff , Major Pierre , Bonert Michael , Kapoor Anil , Tang Damu 
Published: January 2023

Abstract
Background
PCSK9 regulates cholesterol homeostasis and promotes tumorigenesis. However, the relevance of these two actions and the mechanisms underlying PCSK9’s oncogenic roles in melanoma and other cancers remain unclear.

Methods
PCSK9’s association with melanoma was analysed using the TCGA dataset. Empty vector (EV), PCSK9, gain-of-function (D374Y), and loss-of-function (Q152H) PCSK9 mutant were stably-expressed in murine melanoma B16 cells and studied for impact on B16 cell-derived oncogenesis in vitro and in vivo using syngeneic C57BL/6 and Pcsk9−/− mice. Intratumoral accumulation of cholesterol was determined. RNA-seq was performed on individual tumor types. Differentially-expressed genes (DEGs) were derived from the comparisons of B16 PCSK9, B16 D374Y, or B16 Q152H tumors to B16 EV allografts and analysed for pathway alterations.

Results
PCSK9 expression and its network negatively correlated with the survival probability of patients with melanoma. PCSK9 promoted B16 cell proliferation, migration, and growth in soft agar in vitro, formation of tumors in C57BL/6 mice in vivo, and accumulation of intratumoral cholesterol in a manner reflecting its regulation of the low-density lipoprotein receptor (LDLR): Q152H, EV, PCSK9, and D374Y. Tumor-associated T cells, CD8 + T cells, and NK cells were significantly increased in D374Y tumors along with upregulations of multiple immune checkpoints, IFNγ, and 143 genes associated with T cell dysfunction. Overlap of 36 genes between the D374Y DEGs and the PCSK9 DEGs predicted poor prognosis of melanoma and resistance to immune checkpoint blockade (ICB) therapy. CYTH4, DENND1C, AOAH, TBC1D10C, EPSTI1, GIMAP7, and FASL (FAS ligand) were novel predictors of ICB therapy and displayed high level of correlations with multiple immune checkpoints in melanoma and across 30 human cancers. We observed FAS ligand being among the most robust biomarkers of ICB treatment and constructed two novel and effective multigene panels predicting response to ICB therapy. The profiles of allografts produced by B16 EV, PCSK9, D374Y, and Q152H remained comparable in C57BL/6 and Pcsk9−/− mice.

Conclusions
Tumor-derived PCSK9 plays a critical role in melanoma pathogenesis. PCSK9’s oncogenic actions are associated with intratumoral cholesterol accumulation. PCSK9 systemically affects the immune system, contributing to melanoma immune evasion. Novel biomarkers derived from the PCSK9-network effectively predicted ICB therapy responses.
Interactive effects of intrinsic capacity and obesity on the KDIGO chronic kidney disease risk classification in older patients with type 2 diabetes mellitus
Authors: Tang Wei-Hua , Yu Teng-Hung , Lee Hui-Lan , Lee Yau-Jiunn 
Published: January 2023

AbstractBackgroundIntrinsic capacity (IC) is a novel concept focusing on normal and healthy aging. The effect of IC on the risk of chronic kidney disease (CKD) according to KDIGO category in older type 2 diabetes mellitus (T2DM) patients has rarely been studied. We investigated whether a decline in IC is associated with the risk of CKD according to KDIGO 2012 categories.MethodsThis is a cross-sectional study. The exposure variables (IC score and body mass index) and outcome variable (KDIGO categories of the risk of CKD) were collected at the same timepoint. A total of 2482 older subjects with T2DM managed through a disease care program were enrolled. The five domains of IC, namely locomotion, cognition, vitality, sensory, and psychological capacity were assessed. Based on these domains, the IC composite score was calculated. CKD risk was classified according to the KDIGO 2012 CKD definition. Univariate and multivariate analyses were used to assess the association between IC score and KDIGO categories of risk of CKD.ResultsThe KDIGO CKD risk category increased in parallel with IC score (p for trend < 0.0001). In multivariate analysis, compared to those with an IC score 0, the odds ratio of having a KDIGO moderately increased to very high risk category of CKD was 1.76 (1.31–2.37) times higher for those with an IC score of 2–5. Furthermore, an increased IC score was associated with a higher prevalence of moderate and severe obesity. Moreover, there was a synergistic interaction between IC score and obesity on the KDIGO moderately increased to very high risk category of CKD (synergy index = 1.683; 95% CI 0.630–3.628), and the proportion of the KDIGO moderately increased to very high risk category of CKD caused by this interaction was 25.6% (attributable proportion of interaction = 0.256).ConclusionsOur findings indicate that IC score may be closely related to the KDIGO moderately increased to very high risk category of CKD. In addition, there may be a synergistic interaction between IC score and obesity, and this synergistic interaction may increase the KDIGO CKD risk stage.
Study of microencapsulated fatty acid antimicrobial activity in vitro and its prevention ability of Clostridium perfringens induced necrotic enteritis in broiler chicken
Authors: Qi Nanshan , Liu Shaobing , Yan Fangquan , Chen Bing , Wu Shilin , Lin Xuhui , Yan Zhuanqiang , Zhou Qingfeng , Liao Shenquan , Li Juan , Lv Minna , Cai Haiming , Hu Junjing , Zhang Jianfei , Gu Youfang , Sun Mingfei 
Published: January 2023

Abstract
Background
Necrotic enteritis (NE) is an infectious intestinal disease caused by Clostridium perfringens (C. perfringens) that is now re-emerging and causing concern within the poultry industry. Previously, the supplementation of antibiotics in feed was the most popular control strategy against C. perfringens. However, with the ban on supplementing growth-promoting antibiotics in livestock feed, alternatives to antibiotics will be essential in order to control necrotic enteritis. A possible alternative to antibiotics could be the medium or long chain fatty acids (MCFA or LCFA) as these are able to destroy cell membranes which in turn results in the death of bacteria. In this study, the in vitro antimicrobial activity of different combinations with microencapsulated caprylic acid (C8: 0), capric acid (C10: 0), lauric acid (C12: 0) and myristic acid (C14: 0) against C. perfringens and in vivo control the NE-inducing C. perfringens in broiler chicken were analyzed.

Results
The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) assay results revealed that three different combinations of medium/long chain fatty acids varied in antimicrobial activities against C. perfringens type A strain (CVCC52, quality control), C. perfringens type A strain (C8-1), C. perfringens type G strain (D25) and C. perfringens type G strain (MZ1). Specifically, combination of C12: 0 and C14: 0 (C12–14) showed the highest antimicrobial activity against the four strains of C. perfringens (MIC ≤ 12.5 μg/mL, MBC = 50 μg/mL), followed by the combination of C10: 0 and C12: 0 (C10–12) (MIC, MBC ≤ 50 μg/mL). The in vivo study, 189 of 818-crossbred chickens that were fed a wheat-based diet and randomly divided into nine groups, with six treatment groups supplemented with either a high dose (1 g/kg) or low dose (0.5 g/kg) of three combinations respectively. The remaining three groups comsisted of a positive group supplement with avilamycin (0.01 g/kg), an infected control and an uninfected control. All chickens were challenged with C. perfringens from day 14 to day 17, except those in the uninfected control group. On day 20, the duodenum and jejunum necrotic lesions scores were calculated and the results showed that there was significant decrease in the C12–C14 high dose group (1.43 ± 0.23, 0.48 ± 0.13) and the C10–12 high dose group (1.52 ± 0.19, 0.48 ± 0.11) compared to the infected group (2.86 ± 0.21, 1.20 ± 0.28).

Conclusions
This finding indicated that dietary microencapsulated C12–C14 and C10–C12 could inhibit the growth of C. perfringens in chickens, which proves is viability to serve as an alternative to antibiotics used for necrotic enteritis caused by C. perfringens.
MORTAR: a rich client application for in silico molecule fragmentation
Authors: Bänsch Felix , Schaub Jonas , Sevindik Betül , Behr Samuel , Zander Julian , Steinbeck Christoph , Zielesny Achim 
Published: January 2023

AbstractDeveloping and implementing computational algorithms for the extraction of specific substructures from molecular graphs (in silico molecule fragmentation) is an iterative process. It involves repeated sequences of implementing a rule set, applying it to relevant structural data, checking the results, and adjusting the rules. This requires a computational workflow with data import, fragmentation algorithm integration, and result visualisation. The described workflow is normally unavailable for a new algorithm and must be set up individually. This work presents an open Java rich client Graphical User Interface (GUI) application to support the development of new in silico molecule fragmentation algorithms and make them readily available upon release. The MORTAR (MOlecule fRagmenTAtion fRamework) application visualises fragmentation results of a set of molecules in various ways and provides basic analysis features. Fragmentation algorithms can be integrated and developed within MORTAR by using a specific wrapper class. In addition, fragmentation pipelines with any combination of the available fragmentation methods can be executed. Upon release, three fragmentation algorithms are already integrated: ErtlFunctionalGroupsFinder, Sugar Removal Utility, and Scaffold Generator. These algorithms, as well as all cheminformatics functionalities in MORTAR, are implemented based on the Chemistry Development Kit (CDK).
Graphical Abstract
Are sub-Saharan African national food and agriculture policies nutrition-sensitive? A case study of Ethiopia, Ghana, Malawi, Nigeria, and South Africa
Authors: Asirvatham Roshaany , Demi Suleyman M. , Ezezika Obidimma 
Published: January 2023

Abstract
Background
In sub-Saharan Africa (SSA), malnutrition coupled with rising rates of undernutrition and the burden of overweight/obesity remains one of the most significant public health challenges facing the region. Nutrition-sensitive agriculture can play an important role in reducing malnutrition by addressing the underlying causes of nutrition outcomes. Therefore, we aim to assess the nutrition-sensitivity of food and agriculture policies in SSA and to provide recommendations for identified policy challenges in implementing nutrition-sensitive agriculture initiatives.

Methods
We assessed past and current national policies relevant to agriculture and nutrition from Ethiopia, Ghana, Malawi, Nigeria, and South Africa. Thirty policies and strategies were identified and reviewed after a literature scan that included journal articles, reports, and policy documents on food and agriculture. The policies and strategies were reviewed against FAO’s Key Recommendations for Improving Nutrition Through Agriculture and Food Systems guidelines.

Results
Through the review of 30 policy documents, we found that the link between agriculture and nutrition remains weak, particularly in agriculture policies. The review of the policies highlighted insufficient attention to nutrition and the production of micronutrient-rich foods, lack of strategies to increase farmer market access, and weak multi-sectoral collaboration and capacity building.

Conclusion
Nutrition-sensitive agriculture has received scant attention in previous agricultural and food policies in SSA that were riddled with implementation issues, lack of capacity, and ineffective methods for multi-sector collaboration. Recognition of these challenges are leading countries to revise and create new policies that prioritize nutrition-sensitive agriculture as a key driver in overcoming malnutrition.
Primary upper lumbar hernia repaired by transabdominal preperitoneal approach technique using a self-expanding mesh with a memory-recoil ring, report of a case
Authors: Yamashita Reika , Suwa Katsuhito , Okamoto Tomoyoshi , Eto Ken 
Published: January 2023

Abstract
Background
Upper lumber hernia is a rare entity which can cause obstruction and strangulation. Laparoscopic technique has been considered effective for such hernia repairs; however, there is no report of use of the self-expanding mesh.

Case presentation
A 77-year-old woman visited to our hospital complaining of a bulge of about 5 cm in the left lumbar dorsal region while standing. Abdominal CT and MRI scans showed a fascial defect in the left lumbar abdominal wall and confirmed the presence of a hernia, in which retroperitoneal fatty tissue and the descending colon protruded. Transabdominal preperitoneal repair (TAPP) was performed and the operative findings revealed the hernia orifice, 3 × 2.5 cm in diameter, between two intercostal nerves. To avoid nerve injury or entrapment, the number of mesh fixation was desirable minimum; therefore, a self-expanding mesh with a memory-recoil ring was used. The mesh, 9.5 × 13 cm in diameter, was placed and tacked to the abdominal wall at two points, 1 cm ventral and dorsal to the hernia orifice. The postoperative course was uneventful and no pain or recurrence was observed with follow-up of 6 months.

Conclusion
We herein present a case of upper lumber hernia successfully repaired by TAPP with a self-expanding mesh.
Nutraceutical with a promising oral anticancer effect: in vitro study on apricot oil extract
Authors: Ellithy Marwa Mohamed , Tarek Heba Elsayed , Shalash Heba Nader 
Published: January 2023

Abstract
Background
One of the major threats to human health is malignancy. Treatment regimens usually followed by either chemo or radiotherapy have a wide range of collateral unwanted side effects. Scientists seek alternatives with less or no adverse consequences. Nutraceuticals possess disease-modifying implications in medicine related to Alzheimer’s, cardiovascular, Parkinson’s diseases and malignancy. Apricot oil extract is one such nutraceutical. Its active component is amygdalin, known also as vitamin B.17 or laetrile. It is found in a wide range of vegetable species. Amygdalin is found in high concentration in the kernels of rosaceous fruits such as bitter nuts and apricot kernels. Amygdalin is an aromatic cyanogenic component with a glycoside group. It has a diverse effect on different systems and organs of the body. Recently, it has shown an anticancer potential as it can decompose carcinogenic elements found in the body and kill malignant cells, so it results in cancer growth inhibition. There is a great debate related to the cyanide toxicity of amygdalin. The presented study aims to evaluate apricot oil extract’s impact on squamous cell carcinoma of the tongue, HNO97, while testing its safety on non-tumorigenic oral epithelial cells.

Results
HNO97 cell line viability was markedly decreased. This may be induced by the upregulation of autophagy, apoptosis enhancement as well as cell cycle arrest. Cancer cell migration was also decreased. Apricot oil caused no significant inhibition of normal OEC viability in low doses.

Conclusions
Apricot oil extract from apricot kernel had a notably antitumorigenic impact on oral cancer cells. It may be later subjected to pre- as well as clinical trials.