bluuebunny/crossref_metadata_2025 huggingface dataset:
CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2 and promotes growth and metastasis of pancreatic cancer
Authors: Chen Shi , Yang Can , Wang Zu-Wei , Hu Jian-Fei , Pan Jing-Jing , Liao Cheng-Yu , Zhang Jia-Qiang , Chen Jiang-Zhi , Huang Yi , Huang Long , Zhan Qian , Tian Yi-Feng , Shen Bai-Yong , Wang Yao-Dong
Published: April 2021

Background

Both aberrant alternative splicing and m6A methylation play complicated roles in the development of pancreatic cancer (PC), while the relationship between these two RNA modifications remains unclear.

Methods

RNA sequencing (RNA-seq) was performed using 15 pairs of pancreatic ductal adenocarcinoma (PDAC) tissues and corresponding normal tissues, and Cdc2-like kinases 1 (CLK1) was identified as a significantly upregulated alternative splicing related gene. Real-time quantitative PCR (qPCR) and western blotting were applied to determine the CLK1 levels. The prognostic value of CLK1 was elucidated by Immunohistochemistry (IHC) analyses in two independent PDAC cohorts. The functional characterizations and mechanistic insights of CLK1 in PDAC growth and metastasis were evaluated with PDAC cell lines and nude mice. SR-like splicing factors5250-Ser(SRSF5250-Ser) was identified as an important target phosphorylation site by phosphorylation mass spectrometry. Through transcriptome sequencing, Methyltransferase-like 14exon10(METTL14exon10) and Cyclin L2exon6.3skipping were identified as key alternative splicing events regulated by the CLK1-SRSF5 axis. RIP assays, RNA-pulldown and CLIP-qPCR were performed to confirm molecular interactions and the precise binding sites. The roles of the shift of METTL14exon 10and Cyclin L2exon6.3skipping were surveyed.

Results

CLK1 expression was significantly increased in PDAC tissues at both the mRNA and protein levels. High CLK1 expression was associated with poor prognosis. Elevated CLK1 expression promoted growth and metastasis of PC cells in vitro and in vivo. Mechanistically, CLK1 enhanced phosphorylation on SRSF5250-Ser, which inhibited METTL14exon10skipping while promoted Cyclin L2exon6.3skipping. In addition, aberrant METTL14exon 10skipping enhanced the N6-methyladenosine modification level and metastasis, while aberrant Cyclin L2exon6.3promoted proliferation of PDAC cells.

Conclusions

The CLK1/SRSF5 pathway induces aberrant exon skipping of METTL14 and Cyclin L2, which promotes growth and metastasis and regulates m6A methylation of PDAC cells. This study suggests the potential prognostic value and therapeutic targeting of this pathway in PDAC patients.
Validation of the Critical-Care Pain Observation Tool-Neuro in brain-injured adults in the intensive care unit: a prospective cohort study
Authors: Gélinas Céline , Bérubé Mélanie , Puntillo Kathleen A. , Boitor Madalina , Richard-Lalonde Melissa , Bernard Francis , Williams Virginie , Joffe Aaron M. , Steiner Craig , Marsh Rebekah , Rose Louise , Dale Craig M. , Tsoller Darina M. , Choinière Manon , Streiner David L.
Published: April 2021

Background

Pain assessment in brain-injured patients in the intensive care unit (ICU) is challenging and existing scales may not be representative of behavioral reactions expressed by this specific group. This study aimed to validate the French-Canadian and English revised versions of the Critical-Care Pain Observation Tool (CPOT-Neuro) for brain-injured ICU patients.

Methods

A prospective cohort study was conducted in three Canadian and one American sites. Patients with a traumatic or a non-traumatic brain injury were assessed with the CPOT-Neuro by trained raters (i.e., research staff and ICU nurses) before, during, and after nociceptive procedures (i.e., turning and other) and non-nociceptive procedures (i.e., non-invasive blood pressure, soft touch). Patients who were conscious and delirium-free were asked to provide their self-report of pain intensity (0–10). A first data set was completed for all participants (n = 226), and a second data set (n = 87) was obtained when a change in the level of consciousness (LOC) was observed after study enrollment. Three LOC groups were included: (a) unconscious (Glasgow Coma Scale or GCS 4–8); (b) altered LOC (GCS 9–12); and (c) conscious (GCS 13–15).

Results

Higher CPOT-Neuro scores were found during nociceptive procedures compared to rest and non-nociceptive procedures in both data sets (p < 0.001). CPOT-Neuro scores were not different across LOC groups. Moderate correlations between CPOT-Neuro and self-reported pain intensity scores were found at rest and during nociceptive procedures (Spearman rho > 0.40 and > 0.60, respectively). CPOT-Neuro cut-off scores ≥ 2 and ≥ 3 were found to adequately classify mild to severe self-reported pain ≥ 1 and moderate to severe self-reported pain ≥ 5, respectively. Interrater reliability of raters’ CPOT-Neuro scores was supported with intraclass correlation coefficients > 0.69.

Conclusions

The CPOT-Neuro was found to be valid in this multi-site sample of brain-injured ICU patients at various LOC. Implementation studies are necessary to evaluate the tool’s performance in clinical practice.
Breast adipose tissue macrophages (BATMs) have a stronger correlation with breast cancer survival than breast tumor stroma macrophages (BTSMs)
Authors: Lin Lili , Kuhn Christina , Ditsch Nina , Kolben Thomas , Czogalla Bastian , Beyer Susanne , Trillsch Fabian , Schmoeckel Elisa , Mayr Doris , Mahner Sven , Jeschke Udo , Hester Anna
Published: April 2021

Background

An abundance of tumor-associated macrophages has been shown to be an independent prognostic factor for a poor prognosis of human breast cancer (BC). Adipose tissue accounts for the largest proportion of the breast and has also been identified as an independent indicator of poor survival in BC. This study aims to elucidate if the influence of adipose tissue in BC might be mediated by macrophages. The roles of macrophages in the breast tumor-stroma (breast tumor stroma macrophages, BTSM) and macrophages in the surrounding adipose tissue (breast adipose tissue macrophages, BATM) were explored separately.

Methods

Two hundred ninety-eight BC tissue samples were analyzed immunohistochemically. The number of macrophages was detected by CD68+ staining. The quantity of BATMs and BTSMs was correlated to clinical and pathological parameters as well as to disease-free survival (DFS) and overall survival (OS).

Results

The amounts of BATMs and BTSMs strongly correlated with each other (r = 0.5, p = 2.98E−15). The quantity of BTSMs, but not of BATMs, was significantly associated with the BC molecular subtype (p = 0.000011), and all triple-negative BC tumors contained high amounts of BTSMs. BATMs were negatively associated with DFS (p = 0.0332). Both BATMs (p = 0.000401) and BTSMs (p = 0.021) were negatively associated with OS in the Kaplan-Meier analysis, but only BATMs remained an independent factor in the multivariate Cox-regression analysis (HR = 4.464, p = 0.004). Combining prostaglandin E2 receptor 3 (EP3)-expression and the quantity of BATMs, a subgroup with an extremely poor prognosis could be identified (median OS 2.31 years in the “high BATMs/low EP3” subgroup compared to 11.42 years in the most favorable “low BATMs/high EP3” subgroup, p = 0.000002).

Conclusion

Our findings suggest that BTSMs and BATMs seem to be involved differently in BC. Breast adipose tissue might contribute to the aggressiveness of BC via BATMs, which were independently associated with BC survival. BATMs’ role and occurrence might be functionally dependent on EP3, as a combination of both factors was strongly associated with survival. Targeting BATMs—eventually in combination with targeting the EP3-pathway—might be promising for future therapies.
Comparative regulomics supports pervasive selection on gene dosage following whole genome duplication
Authors: Gillard Gareth B. , Grønvold Lars , Røsæg Line L. , Holen Matilde Mengkrog , Monsen Øystein , Koop Ben F. , Rondeau Eric B. , Gundappa Manu Kumar , Mendoza John , Macqueen Daniel J. , Rohlfs Rori V. , Sandve Simen R. , Hvidsten Torgeir R.
Published: April 2021

Background

Whole genome duplication (WGD) events have played a major role in eukaryotic genome evolution, but the consequence of these extreme events in adaptive genome evolution is still not well understood. To address this knowledge gap, we used a comparative phylogenetic model and transcriptomic data from seven species to infer selection on gene expression in duplicated genes (ohnologs) following the salmonid WGD 80–100 million years ago.

Results

We find rare cases of tissue-specific expression evolution but pervasive expression evolution affecting many tissues, reflecting strong selection on maintenance of genome stability following genome doubling. Ohnolog expression levels have evolved mostly asymmetrically, by diverting one ohnolog copy down a path towards lower expression and possible pseudogenization. Loss of expression in one ohnolog is significantly associated with transposable element insertions in promoters and likely driven by selection on gene dosage including selection on stoichiometric balance. We also find symmetric expression shifts, and these are associated with genes under strong evolutionary constraints such as ribosome subunit genes. This possibly reflects selection operating to achieve a gene dose reduction while avoiding accumulation of “toxic mutations”. Mechanistically, ohnolog regulatory divergence is dictated by the number of bound transcription factors in promoters, with transposable elements being one likely source of novel binding sites driving tissue-specific gains in expression.

Conclusions

Our results imply pervasive adaptive expression evolution following WGD to overcome the immediate challenges posed by genome doubling and to exploit the long-term genetic opportunities for novel phenotype evolution.
Improving cognition in severe mental illness by combining cognitive remediation and transcranial direct current stimulation: study protocol for a pragmatic randomized controlled pilot trial (HEADDSET)
Authors: Poppe Anika , Bais Leonie , van Duin Daniëlle , Ćurčić-Blake Branislava , Pijnenborg Gerdina Hendrika Maria , van der Meer Lisette
Published: April 2021

Background

A fundamental challenge for many people with severe mental illness (SMI) is how to deal with cognitive impairments. Cognitive impairments are common in this population and limit daily functioning. Moreover, neural plasticity in people with SMI appears to be reduced, a factor that might hinder newly learned cognitive skills to sustain. The objective of this pilot trial is to investigate the effects of cognitive remediation (CR) on cognitive and daily functioning in people dependent on residential settings. In addition, transcranial direct current stimulation (tDCS) is used to promote neural plasticity. It is expected that the addition of tDCS can enhance learning and will result in longer-lasting improvements in cognitive and daily functioning.

Methods

This is a pragmatic, triple-blinded, randomized, sham-controlled, pilot trial following a non-concurrent multiple baseline design with the participants serving as their own control. We will compare (1) CR to treatment as usual, (2) active/sham tDCS+CR to treatment as usual, and (3) active tDCS+CR to sham tDCS+CR. Clinical relevance, feasibility, and acceptability of the use of CR and tDCS will be evaluated. We will recruit 26 service users aged 18 years or older, with a SMI and dependent on residential facilities. After a 16-week waiting period (treatment as usual), which will serve as a within-subject control condition, participants will be randomized to 16 weeks of twice weekly CR combined with active (N = 13) or sham tDCS (N = 13). Cognitive, functional, and clinical outcome assessments will be performed at baseline, after the control (waiting) period, directly after treatment, and 6-months post-treatment.

Discussion

The addition of cognitive interventions to treatment as usual may lead to long-lasting improvements in the cognitive and daily functioning of service users dependent on residential facilities. This pilot trial will evaluate whether CR on its own or in combination with tDCS can be a clinically relevant addition to further enhance recovery. In case the results indicate that cognitive performance can be improved with CR, and whether or not tDCS will lead to additional improvement, this pilot trial will be extended to a large randomized multicenter study.

Trial registration

Dutch Trial Registry NL7954. Prospectively registered on August 12, 2019.
Accuracy, patient-perceived usability, and acceptance of two symptom checkers (Ada and Rheport) in rheumatology: interim results from a randomized controlled crossover trial
Authors: Knitza Johannes , Mohn Jacob , Bergmann Christina , Kampylafka Eleni , Hagen Melanie , Bohr Daniela , Morf Harriet , Araujo Elizabeth , Englbrecht Matthias , Simon David , Kleyer Arnd , Meinderink Timo , Vorbrüggen Wolfgang , von der Decken Cay Benedikt , Kleinert Stefan , Ramming Andreas , Distler Jörg H. W. , Vuillerme Nicolas , Fricker Achim , Bartz-Bazzanella Peter , Schett Georg , Hueber Axel J. , Welcker Martin
Published: April 2021

Background

Timely diagnosis and treatment are essential in the effective management of inflammatory rheumatic diseases (IRDs). Symptom checkers (SCs) promise to accelerate diagnosis, reduce misdiagnoses, and guide patients more effectively through the health care system. Although SCs are increasingly used, there exists little supporting evidence.

Objective

To assess the diagnostic accuracy, patient-perceived usability, and acceptance of two SCs: (1) Ada and (2) Rheport.

Methods

Patients newly presenting to a German secondary rheumatology outpatient clinic were randomly assigned in a 1:1 ratio to complete Ada or Rheport and consecutively the respective other SCs in a prospective non-blinded controlled randomized crossover trial. The primary outcome was the accuracy of the SCs regarding the diagnosis of an IRD compared to the physicians’ diagnosis as the gold standard. The secondary outcomes were patient-perceived usability, acceptance, and time to complete the SC.

Results

In this interim analysis, the first 164 patients who completed the study were analyzed. 32.9% (54/164) of the study subjects were diagnosed with an IRD. Rheport showed a sensitivity of 53.7% and a specificity of 51.8% for IRDs. Ada’s top 1 (D1) and top 5 disease suggestions (D5) showed a sensitivity of 42.6% and 53.7% and a specificity of 63.6% and 54.5% concerning IRDs, respectively. The correct diagnosis of the IRD patients was within the Ada D1 and D5 suggestions in 16.7% (9/54) and 25.9% (14/54), respectively. The median System Usability Scale (SUS) score of Ada and Rheport was 75.0/100 and 77.5/100, respectively. The median completion time for both Ada and Rheport was 7.0 and 8.5 min, respectively. Sixty-four percent and 67.1% would recommend using Ada and Rheport to friends and other patients, respectively.

Conclusions

While SCs are well accepted among patients, their diagnostic accuracy is limited to date.

Trial registration

DRKS.de, DRKS00017642. Registered on 23 July 2019
Diversity of 3′ variable region of cagA gene in Helicobacter pylori strains isolated from Chinese population
Authors: Xue Zhijing , You Yuanhai , He Lihua , Gong Yanan , Sun Lu , Han Xiurui , Fan Ruyue , Zhai Kangle , Yang Yaming , Zhang Maojun , Yan Xiaomei , Zhang Jianzhong
Published: April 2021

Background

The cytotoxin-associated gene A (cagA) is one of the most important virulence factors ofHelicobacter pylori(H. pylori). There is a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal of CagA protein. This repeat region is thought to play an important role in the pathogenesis of gastrointestinal diseases. The aim of this study was to investigate the diversity ofcagA3′ variable region and the amino acid polymorphisms in the EPIYA segments of the CagA C-terminal region ofH. pylori, and their association with gastroduodenal diseases.

Methods

A total of 515H. pyloristrains from patients in 14 different geographical regions of China were collected. The genomic DNA from each strain was extracted and thecagA3′ variable region was amplified by polymerase chain reaction (PCR). The PCR products were sequenced and analyzed using MEGA 7.0 software.

Results

A total of 503 (97.7%)H. pyloristrains werecagA-positive and 1,587 EPIYA motifs were identified, including 12 types of EPIYA or EPIYA-like sequences. In addition to the four reported major segments, several rare segments (e.g., B′, B″ and D′) were defined and 20 different sequence types (e.g., ABD, ABC) were found in our study. A total of 481 (95.6%) strains carried the East Asian type CagA, and the ABD subtypes were most prevalent (82.1%). Only 22 strains carried the Western type CagA, which included AC, ABC, ABCC and ABCCCC subtypes. The CagA-ABD subtype had statistical difference in different geographical regions (P = 0.006). There were seven amino acid polymorphisms in the sequences surrounding the EPIYA motifs, among which amino acids 893 and 894 had a statistical difference with gastric cancer (P = 0.004).

Conclusions

In this study, 503 CagA sequences were studied and analyzed in depth. In Chinese population, mostH. pyloristrains were of the CagA-ABD subtype and its presence was associated with gastroduodenal diseases. Amino acid polymorphisms at residues 893 and 894 flanking the EPIYA motifs had a statistically significant association with gastric cancer.
Vasovagal syncope related to pain procedures in a pain clinic at a tertiary Lebanese hospital between 2016 and 2019
Authors: Kamar Sara , Hallit Souheil , Chamandi Souheil
Published: April 2021

Objectives

Our study focuses on evaluating the factors associated with vasovagal syncope (VVS) when having a pain procedure at the pain clinic as well as showing variation in vital signs associated with fainting across different periods of the procedure (before, during and after).A retrospective case control study was conducted in a university hospital in Lebanon (CHU-NDS) on adult Lebanese patients with data taken from the archives covering a 4 year period (2016–2019).

Results

The multivariable analysis showed that a higher systolic blood pressure per-procedure was significantly associated with lower odds of having vasovagal syncope. An adequate dose of a vasopressor like ephedrine can be used to prevent a vasovagal event from happening. In our study the blood pressure component was more significant than the heart rate component which stayed in the normal range limit in the three different periods of procedure. Cases having a pain procedure for the first time represent 59.6% of the occurrence of VVS. Vasovagal syncope is a complication that can be prevented in high risk patients. Our study suggests taking preventive measures for VVS for patients with first time infiltration status especially if appearing in an anxious state.
Quantitative assessment of the association between erector spinae muscle and in-hospital mortality in elderly patients with pulmonary tuberculosis
Authors: Tanaka Ai , Komiya Kosaku , Yamasue Mari , Ando Yumiko , Takeno Yukiko , Takikawa Shuichi , Hiramatsu Kazufumi , Kadota Jun-ichi
Published: April 2021

Objective

Skeletal muscle size is considered a predictor of prognosis in patients with respiratory diseases including Mycobacterium avium complex lung disease. However, no research focused on its impact on prognosis in patients with pulmonary tuberculosis (TB). Thus, this study aimed to assess the association between erector spinae muscle (ESM) size and in-hospital mortality among patients with pulmonary TB.

Results

We retrospectively included 258 consecutive patients aged over 65 years old, who were admitted to the hospital for bacteriologically confirmed pulmonary TB, and all underwent chest computed tomography (CT) scan upon admission. The cross-sectional area of the ESM (ESMcsa) was measured at the lower margin of the 12th thoracic vertebra on a single-slice CT scan image and was adjusted according to body surface area (BSA). In total, 71 (28%) patients died during hospitalization. The non-survivor group had a high incidence of respiratory failure and comorbidities and lower hemoglobin and albumin levels, performance status score, and ESMcsa/BSA. Multivariate analysis revealed that low performance status score and hemoglobin and albumin levels, but not ESMcsa/BSA and body mass index, could independently predict in-hospital mortality after adjusting for age and comorbidities. Therefore, ESM size was not associated with in-hospital mortality in patients with pulmonary TB.
Composite lymphoma of T-cell rich, histiocyte-rich diffuse large B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma: a case report
Authors: Esper Asil , Alhoulaiby Sami , Zuhri Yafi Ruba , Alshehabi Zuheir
Published: April 2021

Background

Composite lymphoma is a rare entity where two or more distinct subtypes of lymphoma coexist within a single organ or tissue.

Case presentation

We report a new case of a 67-year-old Caucasian male patient, who presented with fatigue, weakness, weight loss, and polyuria. He also had epigastric and left lumbar pain, enlarged spleen, and enlarged left axillary lymph node on examination, with no relevant medical or familial history.

A biopsy from the node showed an appearance of T-cell rich, histiocyte-rich diffuse large B-cell lymphoma and nodular lymphocyte predominant Hodgkin lymphoma.

The patient was initially treated with adriamycin (doxorubicin), bleomycin, vinblastine, dacarbazine chemotherapy regimen, then switched to rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone regimen.

During the therapy, some regression was noticed, especially in the size of the splenic enlargement; however, the patient died 2 months after completing the regimen.

Conclusion

Composite lymphomas should continue to be studied. Also, treatment is still debatable in type, efficacy, and outcomes.
Sinusoidal electromagnetic fields accelerate bone regeneration by boosting the multifunctionality of bone marrow mesenchymal stem cells
Authors: Li Weigang , Liu Wenbin , Wang Wei , Wang Jiachen , Ma Tian , Chen Jingyuan , Wu Hua , Liu Chaoxu
Published: April 2021

Background

The repair of critical-sized bone defects is always a challenging problem. Electromagnetic fields (EMFs), used as a physiotherapy for bone defects, have been suspected to cause potential hazards to human health due to the long-term exposure. To optimize the application of EMF while avoiding its adverse effects, a combination of EMF and tissue engineering techniques is critical. Furthermore, a deeper understanding of the mechanism of action of EMF will lead to better applications in the future.

Methods

In this research, bone marrow mesenchymal stem cells (BMSCs) seeded on 3D-printed scaffolds were treated with sinusoidal EMFs in vitro. Then, 5.5 mm critical-sized calvarial defects were created in rats, and the cell scaffolds were implanted into the defects. In addition, the molecular and cellular mechanisms by which EMFs regulate BMSCs were explored with various approaches to gain deeper insight into the effects of EMFs.

Results

The cell scaffolds treated with EMF successfully accelerated the repair of critical-sized calvarial defects. Further studies revealed that EMF could not directly induce the differentiation of BMSCs but improved the sensitivity of BMSCs to BMP signals by upregulating the quantity of specific BMP (bone morphogenetic protein) receptors. Once these receptors receive BMP signals from the surrounding milieu, a cascade of reactions is initiated to promote osteogenic differentiation via the BMP/Smad signalling pathway. Moreover, the cytokines secreted by BMSCs treated with EMF can better facilitate angiogenesis and osteoimmunomodulation which play fundamental roles in bone regeneration.

Conclusion

In summary, EMF can promote the osteogenic potential of BMSCs and enhance the paracrine function of BMSCs to facilitate bone regeneration. These findings highlight the profound impact of EMF on tissue engineering and provide a new strategy for the clinical treatment of bone defects.
Identification of circulating CD31+CD45+ cell populations with the potential to differentiate into erythroid cells
Authors: Monaco Maria Chiara G. , Maric Dragan , Salvucci Ombretta , Passeri Cristina Antonetti Lamorgese , Accorsi Patrizia , Major Eugene O. , Berardi Anna Concetta
Published: April 2021

Erythro-myeloid progenitors (EMP) are found in a population of cells expressing CD31 and CD45 markers (CD31+CD45+). A recent study indicated that EMPs persist until adulthood and can be a source of endothelial cells. We identified two sub-populations of EMP cells, CD31lowCD45low and CD31highCD45+, from peripheral blood that can differentiate into cells of erythroid lineage. Our novel findings add to the current knowledge of hematopoietic lineage commitment, and our sequential, dual-step, in vitro culture model provides a platform for the study of the molecular and cellular mechanisms underlying human hematopoiesis and erythroid differentiation.
On a time fractional diffusion with nonlocal in time conditions
Authors: Tuan Nguyen Hoang , Triet Nguyen Anh , Luc Nguyen Hoang , Phuong Nguyen Duc
Published: April 2021

In this work, we consider a fractional diffusion equation with nonlocal integral condition. We give a form of the mild solution under the expression of Fourier series which contains some Mittag-Leffler functions. We present two new results. Firstly, we show the well-posedness and regularity for our problem. Secondly, we show the ill-posedness of our problem in the sense of Hadamard. Using the Fourier truncation method, we construct a regularized solution and present the convergence rate between the regularized and exact solutions.
Global research activity on antimicrobial resistance in food-producing animals
Authors: Sweileh Waleed M.
Published: April 2021

Background

Antimicrobial resistance (AMR) is a global challenge that requires a “One Health” approach to achieve better public health outcomes for people, animals, and the environment. Numerous bibliometric studies were published on AMR in humans. However, none was published in food-producing animals. The current study aimed at assessing and analyzing scientific publications on AMR in food-producing animals.

Method

A validated search query was developed and entered in Scopus advanced search function to retrieve and quantitatively analyze relevant documents. Bibliometric indicators and mapping were presented. The study period was from 2000 to 2019.

Results

The search query retrieved 2852 documents. During the period from 2015 to 2019, approximately 48% of the retrieved documents were published. The article about the discovery of plasmid-mediated colistin resistance in pigs received the highest number of citations (n = 1970). The Journal of Food Protection (n = 123; 4.3%) ranked first in the number of publications while the Applied and Environmental Microbiology journal ranked first in the number of citations per document. The USA led with 576 (20.2%) documents followed by China (n = 375; 13.1%). When the number of publications was standardized by income and population size, India (n = 51.5) ranked first followed by China (n = 38.3) and Brazil (n = 13.4). The growth of publications from China exceeded that of the USA in the last 3 years of the study period. Research collaboration in this field was inadequate. Mapping author keywords showed that E. coli, Salmonella, poultry, Campylobacter, chicken, cattle, and resistant genes were most frequent. The retrieved documents existed in five research themes. The largest research theme was about AMR in Salmonella in food-producing animals. The most recent research theme was about the dissemination and molecular transfer of AMR genes into the environment and among different bacterial strains.

Conclusion

Hot spots of research on AMR in food-producing animals match the world regions of reported hot spots of AMR in animals. Research collaboration in this field is of great importance, especially with low- and middle-income countries. Data on AMR need to be collected nationally and internationally to implement the “One Health” approach in the fight against AMR.
Alcohol consumption and dependence is linked to the extent that people experience need satisfaction while drinking alcohol in two Aboriginal and Torres Strait Islander communities
Authors: Conigrave James H. , Bradshaw Emma L. , Conigrave Katherine M. , Ryan Richard M. , Wilson Scott , Perry Jimmy , Doyle Michael F. , Lee K. S. Kylie
Published: April 2021

Background

Unhealthy alcohol use is a key concern for Aboriginal and Torres Strait Islander (‘Indigenous Australian’) communities. Due to systematic disadvantage and inter-generational trauma, Indigenous Australians may be less likely to have satisfied basic psychological needs (autonomy, competence, and relatedness). When people are need-thwarted, they may engage in compensatory behaviours to feel better in the short-term. We explore the relationship between perceived basic psychological needs satisfaction and alcohol consumption use among Indigenous Australians. Better understanding the functions that alcohol may play for some Indigenous Australian drinkers may aid communities, clinicians, and policy makers in improving programs for reducing drinking-related harms.

Methods

We performed a cross-sectional survey of Indigenous Australians (aged 16 years or older) living in two South Australian communities. Participants were eligible if they had consumed any alcohol in the past 12 months. Spearman correlations and linear regressions were used to determine if feeling more autonomous, competent, and related to others (need satisfied) while drinking, was linked to alcohol consumption and dependence.

Results

Controlling for participant demographics, reporting feeling need satisfied while drinking was linked to drinking more alcohol per day, reporting more frequent symptoms of alcohol dependence, spending more money on alcohol, and scoring higher on the AUDIT-C.

Conclusions

Unhealthy drinking may partly stem from attempts to satisfy basic psychological needs. Programs which support Indigenous Australians to meet basic psychological needs could reduce attempts to meet psychological needs through alcohol consumption.
Amyloid precursor protein elevates fusion of promyelocytic leukemia nuclear bodies in human hippocampal areas with high plaque load
Authors: Marks David , Heinen Natalie , Bachmann Lisa , Meermeyer Sophia , Werner Michelle , Gallego Lucia , Hemmerich Peter , Bader Verian , Winklhofer Konstanze F. , Schröder Elisabeth , Knauer Shirley K. , Müller Thorsten
Published: April 2021

The amyloid precursor protein (APP) is a type I transmembrane protein with unknown physiological function but potential impact in neurodegeneration. The current study demonstrates that APP signals to the nucleus causing the generation of aggregates consisting of its adapter protein FE65, the histone acetyltransferase TIP60 and the tumour suppressor proteins p53 and PML. APP C-terminal (APP-CT50) complexes co-localize and co-precipitate with p53 and PML. The PML nuclear body generation is induced and fusion occurs over time depending on APP signalling and STED imaging revealed active gene expression within the complex. We further show that the nuclear aggregates of APP-CT50 fragments together with PML and FE65 are present in the aged human brain but not in cerebral organoids differentiated from iPS cells. Notably, human Alzheimer’s disease brains reveal a highly significant reduction of these nuclear aggregates in areas with high plaque load compared to plaque-free areas of the same individual. Based on these results we conclude that APP-CT50 signalling to the nucleus takes place in the aged human brain and is involved in the pathophysiology of AD.
Validation of 18F-FDG PET/MRI and diffusion-weighted MRI for estimating the extent of peritoneal carcinomatosis in ovarian and endometrial cancer -a pilot study
Authors: Jónsdóttir Björg , Ripoll Montserrat Alemany , Bergman Antonina , Silins Ilvars , Poromaa Inger Sundström , Ahlström Håkan , Stålberg Karin
Published: April 2021

Background

The extent of peritoneal carcinomatosis is difficult to estimate preoperatively, but a valid measure would be important in identifying operable patients.

The present study set out to validate the usefulness of integrated 18F-FDG PET/MRI, in comparison with diffusion-weighted MRI (DW-MRI), for estimation of the extent of peritoneal carcinomatosis in patients with gynaecological cancer.

Methods

Whole-body PET/MRI was performed on 34 patients with presumed carcinomatosis of gynaecological origin, all scheduled for surgery. Two radiologists evaluated the peritoneal cancer index (PCI) on PET/MRI and DW-MRI scans in consensus. The surgeon estimated PCI intraoperatively, which was used as the gold standard.

Results

Median total PCI for PET/MRI (21.5) was closer to surgical PCI (24.5) (p = 0.6), than DW-MRI (median PCI 20.0, p = 0.007). However, both methods were highly correlated with the surgical PCI (PET/MRI: β = 0.94 p < 0.01, DW-MRI: β = 0.86, p < 0.01). PET/MRI was more accurate (p = 0.3) than DW-MRI (p = 0.001) when evaluating patients at primary diagnosis but no difference was noted in patients treated with chemotherapy. PET/MRI was superior in evaluating high tumour burden in inoperable patients. In the small bowel regions, there was a tendency of higher sensitivity but lower specificity in PET/MRI compared to DW-MRI.

Conclusions

Our results suggest that FDG PET/MRI is superior to DW-MRI in estimating total spread of carcinomatosis in gynaecological cancer. Further, the greatest advantage of PET/MRI seems to be in patients at primary diagnosis and with high tumour burden, which suggest that it could be a useful tool when deciding about operability in gynaecological cancer.
Vaccine market and production capabilities in the Americas
Authors: Ortiz-Prado Esteban , Espín Estefanía , Vásconez Jorge , Rodríguez-Burneo Nathalia , Kyriakidis Nikolaos C. , López-Cortés Andrés
Published: April 2021

In the Americas, The United States of America, Canada, Mexico, and Brazil are the top vaccine producers and the countries with the leading infrastructure for biological manufacturing. The North American countries have the most demanding legislation regulating and controlling these pharmaceuticals’ distribution and production. Some Latin American countries rank in the top 20 of worldwide vaccine manufacturers, with Cuba, Brazil, México and Colombia have a self-sufficient vaccine production of 72.7%, 54,2%; 25%; and 7.7%, respectively, of the national vaccine demand. On the other hand, the rest of Latin American countries cannot satisfy their demand for vaccines, and most of their efforts are associated with the distribution within their health systems rather than in transferring technology.

Based on this literature review, the results suggest an increasing growth vaccine demand, not only for their growing populations and previously established demand but also for the recently exerted pressure due to the COVID-19 pandemic.

Because the American continent has a marked inequality between the hegemonic producers of vaccines, the exporters, and those that depend heavily on importing these products, this could assert technological dependence in countries with rapid population growth and jeopardize the effectiveness of the two vaccination plans.
Toxicity study and anti-trypanosomal activities of aqueous and methanol whole plant extracts of Brillantaisia owariensis on Trypanosoma brucei-induced infection in BALB/c mice
Authors: Ayawa Nafisa Garba , Ramon-Yusuf Suleiman Babatunde , Wada Yunusa Adamu , Oniye Sonnie Joshua , Shehu Dalhatu Mukhtari
Published: April 2021

Background

The problem of drug resistance and toxicity in trypanosomiasis is ever-increasing, thereby creating a need to search for efficacious and safer alternatives that are of plant origin. We designed the present study to assess the oral acute toxicity, and anti-trypanosomal activity of Brillantaisia owariensis in mice.

Methods

Fifty-eight BALB/c mice were used for this study. For toxicity assessment, eighteen mice were divided into two groups of nine mice each, and acute single oral administration of the aqueous and methanol whole plant extracts of B. owariensis was assessed for each group as per Lorke’s method. Mice were observed for signs of toxicity of liver and kidney organs after two weeks of oral administration. For the anti-trypanosomal activity, forty mice were divided into eight groups of five mice. Mouse in each group was inoculated with 0.1 mL containing106T. brucei /mL. Following patency of 3 days, mice were treated at different dosages of methanol and aqueous extracts. Pre-infection, post-infection, and post-treatment data for rectal temperature, body weight, parasiteamia level, packed cell volume, and daily survival were monitored.

Results

The acute oral toxicity studies (LD50) for methanol and aqueous plant extracts in this study were calculated as 3535 mg/kg/body weight, and are non-toxic. No obvious histopathologic observation in the liver and kidney tissues. The mean daily rectal temperature and mean weights of all the treated mice were restored to normal values and significant (P, 0.05) in comparison to the positive control.

Parasitaemia clearance by both extracts was suppressive. The mean PCV values were significantly increased following treatment, and there was prolonged survival especially in mice treated with methanol extracts.

Conclusion

The study concludes that the extracts of B. owariensis are relatively non-toxic with a good safety margin when administered to mice orally. Crude methanol extract exhibited better suppressive and haematinic antitrypanosomal activities than the aqueous extract, and it has a promising effect by its ability to reduce anaemia in mice challenged with T. brucei brucei, and prolonged survival.
The second pregnancy has no effect in the incidence of macrosomia: a cross-sectional survey in two western Chinese regions
Authors: Luo Li , Zeng Huan , Zeng Mao , Liu Xueqing , Xu Xianglong , Wang Lianlian , Zhao Yong
Published: April 2021

Background

After the implementation of the universal two-child policy in China, the increase in parity has led to an increase in adverse pregnancy outcomes. The impact of one and two fetuses on the incidence of fetal macrosomia has not been fully confirmed in China. This study aimed to explore the differences in the incidence of fetal macrosomia in first and second pregnancies in Western China after the implementation of the universal two-child policy.

Methods

A total of 1598 pregnant women from three hospitals were investigated by means of a cross-sectional study from August 2017 to January 2018. Participants were recruited by convenience and divided into first and second pregnancy groups. These groups included 1094 primiparas and 504 women giving birth to their second child. Univariate and multivariate logistic regression analyses were performed to discuss the differences in the incidence of fetal macrosomia in first and second pregnancies.

Results

No significant difference was found in the incidence of macrosomia in the first pregnancy group (7.2%) and the second pregnancy group (7.1%). In the second-time pregnant mothers, no significant association was found between the macrosomia of the second child (5.5%) and that of the first child (4.7%). The multivariate logistic regression model showed that mothers older than 30 years are not likely to give birth to children with macrosomia (odds ratio (OR) 0.6, 95% confidence interval (CI) 0.4,0.9).

Conclusions

The incidence of macrosomia in Western China is might not be affected by the birth of the second child and is not increased by low parity.
Excess epicardial fat volume in women is a novel risk marker for microvascular dysfunction, which may be a contributing factor in the atypical chest pain syndrome
Authors: El Shahawy Mahfouz , Tucker Susan , Izadi Lillee , Sabatini Antonella , Mohan Sukanya
Published: April 2021

Background

Excess epicardial fat volume (EFV) has been recently implicated in cardiovascular structural and functional abnormalities. It has been associated with abnormal microvascular stiffness (as reflected by radial artery waveform; C2), which may result in microvascular dysfunction and contribute to the atypical chest pain syndrome without obstructive coronary artery disease (CAD). Women have been statistically shown to present with atypical chest pain more often than men and specifically without obstructive CAD. The aim of this study is to assess whether excess EFV in female subjects is associated with significant microvascular dysfunction (i.e., C2), in subjects without obstructive CAD.

Results

We screened 596 asymptomatic subjects, ages 20–79, using the Early Cardiovascular Health Risk Scoring System (ECVHRS), which has been reported. Out of the 596 total subjects, 230 subjects had a CACS. Out of these 230 subjects, 77 subjects (45 females; 32 males) had a 0 CACS. The 45 females from this cohort were the subjects of this study, and they were further categorized into 3 groups: group 1 (normal EFV, non-obese female subjects; n=16), females with ECVHRS < 3 and ACC/AHA risk score < 5%; group 2 (n = 9), females with elevated EFV and no abdominal visceral obesity; and group 3 (n=20), females with elevated EFV and abdominal visceral obesity. The average EFV was determined to be 72±20 cm3 among group 1, which indicates the values for normal EFV. The results in group 2 indicate that excess EFV is contributing to the development of microvascular dysfunction, resulting in abnormal micro-arterial (C2) elasticity (p< 0.00001), increase in resting blood pressure (p =0.0001), an abnormal rise in blood pressure (BP) at rest and post-mild protocol exercise (PME) (p = < 0.00001), and abnormal increase in carotid intima-media thickness (CIMT) (p = 0.000164).

Conclusion

Excess EFV appears to be not only a novel cardiovascular risk marker, but also the culprit for other cardiovascular risk markers. Based on these findings, elevated EFV may contribute to the development of the atypical chest pain syndrome in females without obstructive CAD. Additionally, EFV is emerging as a potential clinically relevant significant cardiovascular risk biomarker and may become a target to reduce cardiovascular morbidity and mortality.
Semi-quantitative CT severity scoring as a predictor of development of post-COVID syndrome
Authors: Saad Mohammad A. , El Khateeb Ahmed F. , Ahmed Mona I. , Magdy Ahmed M.
Published: April 2021

Background

Following COVID-19 pandemic, clinical description focused on the clinical presentation of patients in the acute stage of the disease. More recently, data have emerged that some patients continue to experience symptoms related to COVID-19 after the acute phase of infection has subsided (post-COVID syndrome). Although characteristics of post-COVID syndrome have been well described, less is known about the possible invitations during acute illnesses that can predict such syndrome. Our study is a prospective study aiming at assessment of CT severity scoring in the acute phase of COVID-19 pneumonia as a predictor for development of post-COVID syndrome in recovering patients.

Results

A total of 192 symptomatic COVID-19 patients between April 2020 and October 2020 were enrolled in this single-center study, and high-resolution chest CT examinations were evaluated for CT severity scoring. Data were matched with the long-term clinical outcome. CT severity score was significantly higher in patients who developed post-COVID symptoms (p < 0.001). A CT score of > 7 was associated with an increased risk and was found to be predictive of condition development with sensitivity (95.9%), specificity (96%), positive predictive value (95.92%), negative predictive value (96%), and accuracy (95.96%).

Conclusions

CT severity scoring can help in predicting the long-term outcome of COVID-19 patients with cutoff value of CT-SSS > 7 showing highest sensitivity and specificity for predicting development of post-COVID syndrome.
Post-COVID-19 pneumonia lung fibrosis: a worrisome sequelae in surviving patients
Authors: Ali Rasha Mostafa Mohamed , Ghonimy Mai Bahgat Ibrahim
Published: April 2021

Background

Progressive fibrotic lung disease is one of the possible consequences of COVID-19 pulmonary pneumonia, and it is one of the most worrying long-term complications. Pulmonary fibrosis is associated with non-reversible lung dysfunction. The long-term lung changes of previous COVID-19 infection still not completely understood and should be included in further studies. The aim of this study is the early detection and prediction of patients whom may develop such serious complication, thus giving a chance for early introduction of anti-fibrotic drugs.

Results

From April 2020 to December 2020, 80 patients in Cairo, Egypt, who have clinical manifestations and confirmed COVID-19 by PCR, were evaluated by follow-up MDCT. CT image analysis was processed including comparative study using follow-up data (different radiological signs and residual fibrotic changes). Although there was no specific cause for post-COVID-19 lung fibrosis, there were some predicting factors such as old age, cigarette smoking, high CT severity score, and long-term mechanical ventilation.

Conclusion

Early detection of potential cases of post-COVID-19 pulmonary fibrosis may give a chance to prevent or at least modify such disabling complication.
Generalization of level-set inversion to an arbitrary number of geologic units in a regularized least-squares framework
Authors: Giraud Jérémie , Lindsay Mark , Jessell Mark
Published: April 2021

We have developed an inversion method for recovery of the geometry of an arbitrary number of geologic units using a regularized least-squares framework. The method addresses cases in which each geologic unit can be modeled using a constant physical property. Each geologic unit or group assigned the same physical property value is modeled using the signed distance to its interface with other units. We invert for this quantity and recover the location of interfaces between units using the level-set method. We formulate and solve the inverse problem in a least-squares sense by inverting for such signed distances. The sensitivity matrix to perturbations of the interfaces is obtained using the chain rule, and model mapping from the signed distance is used to recover the physical properties. Exploiting the flexibility of the framework that we develop allows any number of rock units to be considered. In addition, it allows the design and use of regularization incorporating prior information to encourage specific features in the inverted model. We apply this general inversion approach to gravity data favoring minimum adjustments of the interfaces between rock units to fit the data. The method is first tested using noisy synthetic data generated for a model compoed of six distinct units, and several scenarios are investigated. It is then applied to field data from the Yerrida Basin (Australia) where we investigate the geometry of a prospective greenstone belt. The synthetic example demonstrates the proof of concept of the proposed methodology, whereas the field application provides insights into, and potential reinterpretation of, the tectonic setting of the area.