bluuebunny/crossref_metadata_2025 huggingface dataset:
A case analysis of partnered research on palliative care for refugees in Jordan and Rwanda
Authors:   the Humanitarian Health Ethics Research Group, de Laat Sonya , Wahoush Olive , Jaber Rania , Khater Wejdan , Musoni Emmanuel , Abu Siam Ibraheem , Schwartz Lisa
Published: January 2021

Background

This case analysis describes dilemmas and challenges of ethical partnering encountered in the process of conducting a research study that explored moral and practical dimensions of palliative care in humanitarian crisis settings. Two contexts are the focus of this case analysis: Jordan, an acute conflict-induced refugee situation, and Rwanda, a protracted conflict-induced refugee setting. The study’s main goal was to better understand ways humanitarian organizations and health care providers might best support ethically and contextually appropriate palliative care in humanitarian contexts. An unintended outcome of the research was learning lessons about ethical dimensions of transnational research partnerships, which is the focus of this case analysis.

Discussion

There exist ongoing challenges for international collaborative research in humanitarian conflict-induced settings. Research partnerships were crucial for connecting with key stakeholders associated with the full study (e.g., refugees with life limiting illness, local healthcare providers, aid organization representatives). While important relationships were established, obstacles limited our abilities to fully attain the type of mutual partnership we aimed for. Unique challenges faced during the research included: (a) building, nurturing and sustaining respectful and equitable research partnerships between collaborators in contexts of cultural difference and global inequality; (b) appropriate ethics review and challenges of responding to local decision-maker’s research needs; and (c) equity and fairness towards vulnerable populations. Research strategies were adapted and applied to respond to these challenges with a specific focus on (d) research rewards and restitution.

Conclusions

This case analysis sheds light on the importance of understanding cultural norms in all research roles, building relationships with decision makers, and developing teams that include researchers from within humanitarian crisis settings to ensure that mutually beneficial research outcomes are ethical as well as culturally and contextually relevant.
Hypoxia-sensitive long noncoding RNA CASC15 promotes lung tumorigenesis by regulating the SOX4/β-catenin axis
Authors: Sun Jianyong , Xiong Yanlu , Jiang Kuo , Xin Bo , Jiang Tongtong , Wei Renji , Zou Yuankang , Tan Hong , Jiang Tao , Yang Angang , Jia Lintao , Wang Lei
Published: January 2021

Background

Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) are involved in the hypoxia-related cancer process and play pivotal roles in enabling malignant cells to survive under hypoxic stress. However, the molecular crosstalk between lncRNAs and hypoxia signaling cascades in non-small cell lung cancer (NSCLC) remains largely elusive.

Methods

Firstly, we identified differentially expressed lncRNA cancer susceptibility candidate 15 (CASC15) as associated with NSCLC based on bioinformatic data. The clinical significance of CASC15 in lung cancer was investigated by Kaplan-Meier survival analysis. Then, we modulated CASC15 expression in NSCLC cell lines by RNAi. CCK-8 and transwell assays were carried out to examine the effects of CASC15 on proliferation and migration of NSCLC cells. Upstream activator and downstream targets of CASC15 were validated by luciferase reporter assay, qRT-PCR, Western blotting, and chromatin immunoprecipitation (ChIP). Lastly, RNA in situ hybridization (RNA-ISH) and immunohistochemistry (IHC) were performed to confirm the genetic relationships between CASC15 and related genes in clinical samples.

Results

CASC15 was highly expressed in NSCLC tissues and closely associated with poor prognosis. Loss-of-function analysis demonstrated that CASC15 was essential for NSCLC cell migration and growth. Mechanistic study revealed that CASC15 was transcriptionally activated by hypoxia signaling in NSCLC cells. Further analysis showed that hypoxia-induced CASC15 transactivation was mainly dependent on hypoxia-inducible factor 1α (HIF-1α) and hypoxia response elements (HREs) located in CASC15 promoter. CASC15 promotes the expression of its chromosomally nearby gene, SOX4. Then SOX4 functions to stabilize β-catenin protein, thereby enhancing the proliferation and migration of NSCLC cells. HIF-1α/CASC15/SOX4/β-catenin pathway was activated in a substantial subset of NSCLC patients.

Conclusions

HIF-1α/CASC15/SOX4/β-catenin axis plays an essential role in the development and progression of NSCLC. The present work provides new evidence that lncRNA CASC15 holds great promise to be used as novel biomarkers for NSCLC. Blocking the HIF-1α/CASC15/SOX4/β-catenin axis can serve as a potential therapeutic strategy for treating NSCLC.
Impact of the acidic environment on gene expression and functional parameters of tumors in vitro and in vivo
Authors: Rauschner Mandy , Lange Luisa , Hüsing Thea , Reime Sarah , Nolze Alexander , Maschek Marcel , Thews Oliver , Riemann Anne
Published: January 2021

Background

The low extracellular pH (pHe) of tumors resulting from glycolytic metabolism is a stress factor for the cells independent from concomitant hypoxia. The aim of the study was to analyze the impact of acidic pHe on gene expression on mRNA and protein level in two experimental tumor lines in vitro and in vivo and were compared to hypoxic conditions as well as combined acidosis+hypoxia.

Methods

Gene expression was analyzed in AT1 prostate and Walker-256 mammary carcinoma of the rat by Next Generation Sequencing (NGS), qPCR and Western blot. In addition, the impact of acidosis on tumor cell migration, adhesion, proliferation, cell death and mitochondrial activity was analyzed.

Results

NGS analyses revealed that 147 genes were uniformly regulated in both cell lines (in vitro) and 79 genes in both experimental tumors after 24 h at low pH. A subset of 25 genes was re-evaluated by qPCR and Western blot. Low pH consistently upregulated Aox1, Gls2, Gstp1, Ikbke, Per3, Pink1, Tlr5, Txnip, Ypel3 or downregulated Acat2, Brip1, Clspn, Dnajc25, Ercc6l, Mmd, Rif1, Zmpste24 whereas hypoxia alone led to a downregulation of most of the genes. Direct incubation at low pH reduced tumor cell adhesion whereas acidic pre-incubation increased the adhesive potential. In both tumor lines acidosis induced a G1-arrest (in vivo) of the cell cycle and a strong increase in necrotic cell death (but not in apoptosis). The mitochondrial O2 consumption increased gradually with decreasing pH.

Conclusions

These data show that acidic pHe in tumors plays an important role for gene expression independently from hypoxia. In parallel, acidosis modulates functional properties of tumors relevant for their malignant potential and which might be the result of pH-dependent gene expression.
Laboratory and microcosm experiments reveal contrasted adaptive responses to ammonia and water mineralisation in aquatic stages of the sibling species Anopheles gambiae (sensu stricto) and Anopheles coluzzii
Authors: Akpodiete Nwamaka Oluchukwu , Tripet Frédéric
Published: January 2021

Background

The sibling species of the malaria mosquito,Anopheles gambiae(sensu stricto) andAnopheles coluzziico-exist in many parts of West Africa and are thought to have recently diverged through a process of ecological speciation with gene flow. Divergent larval ecological adaptations, resulting in Genotype-by-Environment (G × E) interactions, have been proposed as important drivers of speciation in these species. In West Africa,An. coluzziitends to be associated with permanent man-made larval habitats such as irrigated rice fields, which are typically more eutrophic and mineral and ammonia-rich than the temporary rain pools exploited byAn. gambiae(s.s.)

Methods

To highlight G × E interactions at the larval stage and their possible role in ecological speciation of these species, we first investigated the effect of exposure to ammonium hydroxide and water mineralisation on larval developmental success. Mosquito larvae were exposed to two water sources and increasing ammonia concentrations in small containers until adult emergence. In a second experiment, larval developmental success was compared across two contrasted microcosms to highlight G × E interactions under conditions such as those found in the natural environment.

Results

The first experiment revealed significant G × E interactions in developmental success and phenotypic quality for both species in response to increasing ammonia concentrations and water mineralisation. TheAn. coluzziistrain outperformed theAn. gambiae(s.s.) strain under limited conditions that were closer to more eutrophic habitats. The second experiment revealed divergent crisscrossing reaction norms in the developmental success of the sibling species in the two contrasted larval environments. As expected,An. coluzziihad higher emergence rates in the rice paddy environment with emerging adults of superior phenotypic quality compared toAn. gambiae(s.s.), and vice versa, in the rain puddle environment.

Conclusions

Evidence for such G × E interactions lends support to the hypothesis that divergent larval adaptations to the environmental conditions found in man-made habitats such as rice fields inAn. coluzziimay have been an important driver of its ecological speciation.

Graphical Abstract
The Phlebotomus papatasi systemic transcriptional response to trypanosomatid-contaminated blood does not differ from the non-infected blood meal
Authors: Sloan Megan A. , Sadlova Jovana , Lestinova Tereza , Sanders Mandy J. , Cotton James A. , Volf Petr , Ligoxygakis Petros
Published: January 2021

Background

Leishmaniasis, caused by parasites of the genus Leishmania, is a disease that affects up to 8 million people worldwide. Parasites are transmitted to human and animal hosts through the bite of an infected sand fly. Novel strategies for disease control require a better understanding of the key step for transmission, namely the establishment of infection inside the fly.

Methods

The aim of this work was to identify sand fly systemic transcriptomic signatures associated with Leishmania infection. We used next generation sequencing to describe the transcriptome of whole Phlebotomus papatasi sand flies when fed with blood alone (control) or with blood containing one of three trypanosomatids: Leishmania major, L. donovani and Herpetomonas muscarum, the latter being a parasite not transmitted to humans.

Results

Of the trypanosomatids studied, only L. major was able to successfully establish an infection in the host P. papatasi. However, the transcriptional signatures observed after each parasite-contaminated blood meal were not specific to success or failure of a specific infection and they did not differ from each other. The transcriptional signatures were also indistinguishable after a non-contaminated blood meal.

Conclusions

The results imply that sand flies perceive Leishmania as just one feature of their microbiome landscape and that any strategy to tackle transmission should focus on the response towards the blood meal rather than parasite establishment. Alternatively, Leishmania could suppress host responses. These results will generate new thinking around the concept of stopping transmission by controlling the parasite inside the insect.

Graphical Abstract
Validation of loop-mediated isothermal amplification for the detection of Loa loa infection in Chrysops spp in experimental and natural field conditions
Authors: Amambo Glory Ngongeh , Abong Raphael Awah , Fombad Fanny Fri , Njouendou Abdel Jelil , Nietcho Franck , Beng Amuam Andrew , Manuel Ritter , Esum Mathias Eyong , Deribe Kebede , Cho Jerome Fru , Enyong Peter Ivo , Poole Catherine , Hoerauf Achim , Carlow Clotilde , Wanji Samuel
Published: January 2021

Background

The mass drug administration of ivermectin for onchocerciasis control has contributed to a significant drop in Loa loa microfilaria loads in humans that has, in turn, led to reduction of infection levels in Chrysops vectors. Accurate parasite detection is essential for assessing loiasis transmission as it provides a potential alternative or indirect strategy for addressing the problem of co-endemic loiasis and lymphatic filariasis through the Onchocerciasis Elimination Programme and it further reflects the true magnitude of the loiasis problem as excess human mortality has been reported to be associated with the disease. Although microscopy is the gold standard for detecting the infection, the sensitivity of this method is compromised when the intensity of infection is low. The loop-mediated isothermal amplification (LAMP) assay of parasite DNA is an alternative method for detecting infection which offers operational simplicity, rapidity and versatility of visual readout options. The aim of this study was to validate the Loa loa LAMP assay for the detection of infected Chrysops spp. under experimental and natural field conditions.

Methods

Two sets of 18 flies were fed on volunteers with either a low (< 10 mf/ml) or high (> 30,000mf/ml) microfilarial load. The fed flies were maintained under laboratory conditions for 14 days and then analysed using LAMP for the detection of L. loa infection. In addition, a total of 9270 flies were collected from the north-west, east, and south-west regions (SW 1 and 2) of Cameroon using sweep nets and subjected to microscopy (7841 flies) and LAMP (1291 flies plus 138 nulliparous flies) analyses.

Results

The LAMP assay successfully detected parasites in Chrysops fed on volunteers with both low and high microfilariaemic loads. Field validation and surveillance studies revealed LAMP-based infection rates ranging from 0.5 to 31.6%, with the lowest levels in SW 2 and the highest infection rates in SW 1. The LAMP assay detected significantly higher infection rates than microscopy in four of the five study sites.

Conclusion

This study demonstrated the potential of LAMP as a simple surveillance tool. It was found to be more sensitive than microscopy for the detection of experimental and natural L. loa infections in Chrysops vectors.

Graphical Abstract
A severe case of thrombocytopenia, anasarca, fever, renal insufficiency or reticulin fibrosis, and organomegaly syndrome with myocardial and skeletal muscle calcification despite hypocalcemia: a case report
Authors: Minomo Shogo , Fujiwara Yu , Sakashita Shota , Takamura Akito , Nagata Kaoru
Published: January 2021

Background

TAFRO (thrombocytopenia, anasarca, fever, renal insufficiency or reticulin fibrosis, and organomegaly) syndrome is a recently recognized disease with a variety of presentations of variable severity. In acute settings, this disease also involves organ dysfunction because of the associated systemic inflammation. However, cases of TAFRO syndrome with myocardial and/or skeletal muscle calcification have never been reported.

Case presentation

A 24-year-old healthy young Asian man was admitted with intermittent epigastric pain and fever for 2 weeks. Computed tomography revealed pleural effusion, ascites and systemic lymphadenopathy. Laboratory tests showed thrombocytopenia, elevated C-reactive protein, hypoalbuminemia, anemia and renal dysfunction. Based on these findings and bone marrow biopsy, we diagnosed his disease as TAFRO syndrome and commenced hemodialysis for the renal dysfunction. However, he developed refractory hypocalcemia with unstable vital signs, for which we administered calcium gluconate hydrate. Thereafter, myocardial and skeletal muscle calcification was revealed radiologically, with the myocardial calcification causing sick sinus syndrome. He was treated with tocilizumab and finally discharged in an ambulatory condition after prolonged hospitalization, with residual calcific lesions.

Conclusion

This is the first report of a patient with TAFRO syndrome and the complication of organ calcification. The etiology of calcification in this case is not clear. Systemic inflammation with possible hypercytokinemia might have been involved in the unexpected complication of systemic calcification. It is important to carefully handle the general management of TAFRO syndrome because of the possibility of various complications.
Flattening the curves: on-off lock-down strategies for COVID-19 with an application to Brazil
Authors: Tarrataca Luís , Dias Claudia Mazza , Haddad Diego Barreto , De Arruda Edilson Fernandes
Published: January 2021

The current COVID-19 pandemic is affecting different countries in different ways. The assortment of reporting techniques alongside other issues, such as underreporting and budgetary constraints, makes predicting the spread and lethality of the virus a challenging task. This work attempts to gain a better understanding of how COVID-19 will affect one of the least studied countries, namely Brazil. Currently, several Brazilian states are in a state of lock-down. However, there is political pressure for this type of measures to be lifted. This work considers the impact that such a termination would have on how the virus evolves locally. This was done by extending the SEIR model with an on / off strategy. Given the simplicity of SEIR we also attempted to gain more insight by developing a neural regressor. We chose to employ features that current clinical studies have pinpointed has having a connection to the lethality of COVID-19. We discuss how this data can be processed in order to obtain a robust assessment.
Repeatability of two semi-automatic artificial intelligence approaches for tumor segmentation in PET
Authors: Pfaehler Elisabeth , Mesotten Liesbet , Kramer Gem , Thomeer Michiel , Vanhove Karolien , de Jong Johan , Adriaensens Peter , Hoekstra Otto S. , Boellaard Ronald
Published: January 2021

Background

Positron emission tomography (PET) is routinely used for cancer staging and treatment follow-up. Metabolic active tumor volume (MATV) as well as total MATV (TMATV—including primary tumor, lymph nodes and metastasis) and/or total lesion glycolysis derived from PET images have been identified as prognostic factor or for the evaluation of treatment efficacy in cancer patients. To this end, a segmentation approach with high precision and repeatability is important. However, the implementation of a repeatable and accurate segmentation algorithm remains an ongoing challenge.

Methods

In this study, we compare two semi-automatic artificial intelligence (AI)-based segmentation methods with conventional semi-automatic segmentation approaches in terms of repeatability. One segmentation approach is based on a textural feature (TF) segmentation approach designed for accurate and repeatable segmentation of primary tumors and metastasis. Moreover, a convolutional neural network (CNN) is trained. The algorithms are trained, validated and tested using a lung cancer PET dataset. The segmentation accuracy of both segmentation approaches is compared using the Jaccard coefficient (JC). Additionally, the approaches are externally tested on a fully independent test–retest dataset. The repeatability of the methods is compared with those of two majority vote (MV2, MV3) approaches, 41%SUVMAX, and a SUV > 4 segmentation (SUV4). Repeatability is assessed with test–retest coefficients (TRT%) and intraclass correlation coefficient (ICC). An ICC > 0.9 was regarded as representing excellent repeatability.

Results

The accuracy of the segmentations with the reference segmentation was good (JC median TF: 0.7, CNN: 0.73). Both segmentation approaches outperformed most other conventional segmentation methods in terms of test–retest coefficient (TRT% mean: TF: 13.0%, CNN: 13.9%, MV2: 14.1%, MV3: 28.1%, 41%SUVMAX: 28.1%, SUV4: 18.1%) and ICC (TF: 0.98, MV2: 0.97, CNN: 0.99, MV3: 0.73, SUV4: 0.81, and 41%SUVMAX: 0.68).

Conclusion

The semi-automatic AI-based segmentation approaches used in this study provided better repeatability than conventional segmentation approaches. Moreover, both algorithms lead to accurate segmentations for both primary tumors as well as metastasis and are therefore good candidates for PET tumor segmentation.
Visual multiple cross displacement amplification for the rapid identification of S. agalactiae immediately from vaginal and rectal swabs
Authors: Cheng Xueqin , Dou Zhiqian , Yang Jing , Liu Dexi , Gu Yulong , Cai Fenglin , Li Xiaobing , Wang Meifang , Tang Yijun
Published: January 2021

Streptococcus agalactiae (S. agalactiae) is an important pathogen that can lead to neonatus and mother infection. The current existing techniques for the identification of S. agalactiae are limited by accuracy, speed and high-cost. Therefore, a new multiple cross displacement amplification (MCDA) assay was developed for test of the target pathogen immediately from vaginal and rectal swabs. MCDA primers screening were conducted targeting S. agalactiae pcsB gene, and one set of MCDA primers with better rapidity and efficiency was selected for establishing the S. agalactiae-MCDA assay. As a result, the MCDA method could be completed at a constant temperature of 61 °C, without the requirement of special equipment. The detection limit is 250 fg (31.5 copies) per reaction, all S. agalactiae strains displayed positive results, but not for non-S. agalactiae strains. The visual MCDA assay detected 16 positive samples from 200 clinical specimen, which were also detected positive by enrichment/qPCR. While the CHROMagar culture detected 6 positive samples. Thus, the MCDA assay is prefer to enrichment/qPCR and culture for detecting S. agalactiae from clinical specimen. Particularly, the whole test of MCDA takes about 63.1 min, including sample collection (3 min), DNA preparation (15 min), MCDA reaction (45 min) and result reporting (6 s). In addition, the cost was very economic, with only US$ 4.9. These results indicated that our S. agalaciae-MCDA assay is a rapid, sensitive and cost-efficient technique for target pathogen detection, and is more suitable than conventional assays for an urgent detection, especially for 'on-site' laboratories and resource-constrained settings.
Sperm-oocyte interplay: an overview of spermatozoon’s role in oocyte activation and current perspectives in diagnosis and fertility treatment
Authors: Zafar Mohammad Ishraq , Lu Shi , Li Honggang
Published: January 2021

The fertilizing spermatozoon is a highly specialized cell that selects from millions along the female tract until the oocyte. The paternal components influence the oocyte activation during fertilization and are fundamental for normal embryo development; however, the sperm-oocyte interplay is in a continuous debate. This review aims to analyze the available scientific information related to the role of the male gamete in the oocyte activation during fertilization, the process of the interaction of sperm factors with oocyte machinery, and the implications of any alterations in this interplay, as well as the advances and limitations of the reproductive techniques and diagnostic tests. At present, both PLCζ and PAWP are the main candidates as oocyte activated factors during fertilization. While PLCζ mechanism is via IP3, how PAWP activates the oocyte still no clear, and these findings are important to study and treat fertilization failure due to oocyte activation, especially when one of the causes is the deficiency of PLCζ in the sperm. However, no diagnostic test has been developed to establish the amount of PLCζ, the protocol to treat this type of pathologies is broad, including treatment with ionophores, sperm selection improvement, and microinjection with PLCζ protein or RNA.
Does surfactant nebulization prevent early intubation in preterm infants? A protocol for a systematic review and meta-analysis
Authors: Gaertner Vincent D. , Bassler Dirk , Rüegger Christoph M.
Published: January 2021

Background

Respiratory distress syndrome (RDS) is the most common cause of respiratory failure in preterm infants. Treatment consists of respiratory support and exogenous surfactant administration. Commonly, surfactant is administered intratracheally. However, this requires airway instrumentation and subsequent fluid instillation which may be harmful. Surfactant nebulization (SN) may offer a safe and effective alternative for surfactant administration, but the clinical efficacy is not yet established. Thus, this systematic review and meta-analysis of randomized controlled trials will summarize the available evidence to determine the effectiveness and safety of SN for the prevention of intubation and subsequent mechanical ventilation at 72 h after birth.

Methods

A systematic literature search in Medline, Embase, and The Cochrane Library will be performed, and all randomized controlled trials (RCTs) and quasi-RCTs from published articles, presentations, and trial registries will be included in this meta-analysis. Titles and abstracts of all records identified in the search will be screened by two reviewers independently.

Data on preterm infants (≤ 37 weeks) receiving nebulized surfactant in the first 72 h after birth for the treatment or prevention of RDS will be evaluated. Primary outcome is the intubation rate by 72 h after birth, and secondary outcomes include peridosing safety effects as well as major neonatal morbidities.

Risk of bias will be assessed using the revised Cochrane ROB tool, and subgroup analyses will be performed to evaluate potential confounding factors. Publication bias will be assessed by examining a funnel plot. The meta-analysis will be performed using a fixed-effects model.

Discussion

This review will provide an evidence-based tool for information about surfactant nebulization, illustrating the current knowledge and hopefully revealing potential novel avenues for researchers and clinicians alike.

Systematic review registration

This review is registered with the publicly available resource PROSPERO (CRD42020175625).
Multilevel governance energy planning and policy: a view on local energy initiatives
Authors: Dobravec Viktorija , Matak Nikola , Sakulin Christian , Krajačić Goran
Published: January 2021

Background

A sustainable energy system based on renewables, energy-efficiency, decentralisation of energy generation and synergies between different sectors requires new energy planning methods and policies. Energy transition and climate change mitigation achievement can no longer be seen only through top-down activities from a national government. Local and regional governments have a crucial role in delivering public policies relevant to such endeavour. Therefore, the implementation of multilevel governance (MLG) has become a priority for fostering local and regional development more inclusively. Paper analyses the existing energy planning governance in Austria throughout the MLG structure by focusing on the alignment between the local energy and climate initiatives and the national and EU goals. Also, the paper examined the effectiveness of the current MLG structures and outlined the fields where improvements are needed. The successfulness of the MLG approach is shown on Judenburg city case study. Desk research is enhanced by a series of interviews with energy policy experts and implementation of case study measures in TIMES model.

Results

The MLG analysis showed the solid alignment of different governance levels. In contrast, the comparison of the energy and climate initiatives on the local level outlined recommendations for the design of more effective energy planning approach. Four areas of action are identified for further improvement: territorial fragmentation, data availability, spatial energy planning and new integrated MLG. The remaining non-conventional biomass potential of the Murtal region is enough to increase the share of district heating for the residential buildings of the Judenburg city from 16.3 to 30.8% while the building refurbishment increases district heating share to 32%.

Conclusion

Application of MLG analysis demonstrated the alignment of energy targets in Austrian policy on different governance levels. The general willingness of Austrian municipalities to take part in local energy actions was shown through the local initiatives’ analysis. It is argued that strengthening the listed areas of work is necessary to raise the effectiveness of the local initiatives. The case study for the city of Judenburg developed in the TIMES model confirmed that coordinated actions from different levels of governance lead to effective implementation of measures.
An open trial of app-assisted acceptance and commitment therapy (iACT) for eating disorders in type 1 diabetes
Authors: Merwin Rhonda M. , Moskovich Ashley A. , Babyak Michael , Feinglos Mark , Honeycutt Lisa K. , Mooney Jan , Freeman Sara P. , Batchelder Heather , Sangvai Devdutta
Published: January 2021

Background

Eating disorders (EDs) among individuals with type 1 diabetes (T1D) increase the risk of early and severe diabetes-related medical complications and premature death. Conventional eating disorder (ED) treatments have been largely ineffective for T1D patients, indicating the need to tailor treatments to this patient population and the unique conditions under which ED symptoms emerge (in the context of a chronic illness with unrelenting demands to control blood glucose, diet and exercise). The current study was a pilot open trial ofiACT, a novel intervention for EDs in T1D grounded in Acceptance and Commitment Therapy (ACT).iACT was based on the premise that ED symptoms emerge as individuals attempt to cope with T1D and related emotional distress.iACT taught acceptance and mindfulness as an alternative to maladaptive avoidance and control, and leveraged personal values to increase willingness to engage in T1D management, even when it was upsetting (e.g., after overeating). A tailored mobile application (“app”) was used in between sessions to facilitate the application of ACT skills in the moment that individuals are making decisions about their diabetes management.

Methods

Adults with T1D who met criteria for an ED completed 12 sessions ofiACT (with three optional tapering sessions). In addition to examining whether treatment was acceptable and feasible (the primary aim of the study), the study also examined whetheriACT was associated with increased psychological flexibility (i.e., the ability to have distressing thoughts/feelings about diabetes while pursuing personally meaningful values), and improvements in ED symptoms, diabetes management and diabetes distress.

Results

Treatment was acceptable to T1D patients with EDs and feasible to implement. Participants reported increased psychological flexibility with diabetes-related thoughts/feelings, and less obstruction and greater progress in pursuing personal values. There were large effects for change in ED symptoms, diabetes self-management and diabetes distress from baseline to end-of-treatment (Cohen’sd = .90–1.79). Hemoglobin A1calso improved, but thep-value did not reach statistical significance,p = .08.

Conclusions

Findings provide preliminary evidence foriACT to improve outcomes for T1D patients with EDs and support further evaluation of this approach in a controlled trial.

Trial registration

NCT02980627. Registered 8 July 2016.
Family members’ reflections upon a family-based inpatient treatment program for adolescent anorexia nervosa: a thematic analysis
Authors: Nilsen Jan-Vegard , Rø Øyvind , Halvorsen Inger , Oddli Hanne Weie , Hage Trine Wiig
Published: January 2021

Background

Family-based outpatient treatment is usually recommended as the treatment of choice when a child develops anorexia nervosa. However, some young persons will inevitably require higher levels of care. Qualitative research on family perspectives may help inform strategies to adapt family-based practices into intensified treatment settings. Our overarching aim was to investigate family members’ perspectives following a family-based inpatient treatment program for adolescent anorexia nervosa and to discuss clinical implications for treatment providers.

Methods

A subsample of eight families taking part in a naturalistic outcome study at a specialized eating disorder unit participated in the study (8 patients, 14 parents, and 10 siblings). The thematic analyses were inductive, predominantly descriptive, and guided by a multi-perspective framework.

Results

Five main themes were identified: 1: Expectations and evaluation of needs. Entering treatment from different vantage points, 2: Interactions with peers during the admission as highly beneficial or problematic, 3: Perspectives on staff expertise and the eating disorder unit’s structure, 4: Influencing within family relationships in different ways, and 5: Being admitted is at best only half the job: reflections on leaving the eating disorder unit.

Conclusions

Our study offers insight into how former inpatients and their family members experienced an inpatient treatment program designed to align treatment with the central elements of an outpatient family-based treatment approach for adolescent anorexia nervosa. Overall, the findings support emerging research underlining the necessity of strengthening the family-based treatment approach within intensified treatment settings. Moreover, the results emphasized the need for more knowledge on how to optimize inpatient treatment as well as the importance of providing smooth transitions between care settings.
Prevalence and associated factors of internet addiction among undergraduate university students in Ethiopia: a community university-based cross-sectional study
Authors: Zenebe Yosef , Kunno Kunuya , Mekonnen Meseret , Bewuket Ajebush , Birkie Mengesha , Necho Mogesie , Seid Muhammed , Tsegaw Million , Akele Baye
Published: January 2021

Background

Internet addiction is a common problem in university students and negatively affects cognitive functioning, leads to poor academic performance and engagement in hazardous activities, and may lead to anxiety and stress. Behavioral addictions operate on a modified principle of the classic addiction model. The problem is not well investigated in Ethiopia. So the present study aimed to assess the prevalence of internet addiction and associated factors among university students in Ethiopia.

Objectives

Main objective of this study was to assess the prevalence and associated factors of internet addiction among University Students in Ethiopia.

Methods

A community-based cross-sectional study was conducted among Wollo University students from April 10 to May 10, 2019. A total of 603 students were participated in the study using a structured questionnaire. A multistage cluster sampling technique was used to recruit study participants. A binary logistic regression method was used to explore associated factors for internet addiction and variables with apvalue < 0.25 in the bivariate analysis were fitted to the multi-variable logistic regression analysis. The strength of association between internet addiction and associated factors was assessed with odds ratio, 95% CI andpvalue < 0.05 in the final model was considered significant.

Results

The prevalence of internet addiction (IA) among the current internet users was 85% (n = 466). Spending more time on the internet (adjusted odds ratio (AOR) = 10.13, 95% CI 1.33–77.00)), having mental distress (AOR = 2.69, 95% CI 1.02–7.06), playing online games (AOR = 2.40, 95% CI 1.38–4.18), current khat chewing (AOR = 3.34, 95% CI 1.14–9.83) and current alcohol use (AOR = 2.32, 95% CI 1.09–4.92) were associated with internet addiction.

Conclusions

The current study documents a high prevalence of internet addiction among Wollo University students. Factors associated with internet addiction were spending more time, having mental distress, playing online games, current khat chewing, and current alcohol use. As internet addiction becomes an evident public health problem, carrying out public awareness campaigns may be a fruitful strategy to decrease its prevalence and effect. Besides to this, a collaborative work among stakeholders is important to develop other trendy, adaptive, and sustainable countermeasures.
Concurrent chemoradiation in locally advanced primary middle ear lymphoepithelial carcinoma: An effective treatment modality case report
Authors: Fong Pei Yuan , Tan Tiong Yong , Kiong Kimberley Liqin
Published: January 2021

Background

Definitive treatment of primary middle ear lymphoepithelial carcinoma (LEC) is not well established owing to the rarity of this disease entity. We report a case of locally advanced primary middle ear LEC treated with concurrent chemoradiation, with good oncologic outcomes.

Case presentation

A 46 year-old female of Cantonese (Southern Chinese) descent presented with a four-month history of left sided hearing loss and non-pulsatile tinnitus, associated with progressive ipsilateral facial weakness. She had a left facial palsy (House-Brackmann 2) which then deteriorated to complete palsy over 2 weeks. Otoscopic examination of the left ear revealed a red-hued mass replacing the tympanic membrane. There was no cervical lymphadenopathy. Fibreoptic nasoendoscopy was unremarkable. Pure tone audiometry revealed profound mixed left hearing loss with type B impedance. Computed tomography of the temporal bone showed an ill-defined left middle ear mass with erosion of the malleus, tegmen tympani and facial canal. Magnetic Resonance Imaging showed an avidly enhancing lesion involving the dura of the left middle cranial fossa, tympanic and labyrinthine portions of the facial nerve. This mass extended into the apex of the left internal acoustic canal and basal turn of the cochlea. Histopathology confirmed EBV-positive primary middle ear LEC. Concurrent chemoradiation comprising 70Gy of intensity-modulated radiation therapy and 3 cycles of concurrent Cisplatin based chemotherapy over a 6 week period was administered. The patient achieved near-complete disease resolution on 3 month post-treatment imaging. Serum EBV DNA titres declined to undetectable levels and the patient is disease-free at 18 months post-diagnosis.

Discussion and conclusion

Concurrent chemoradiation with curative intent may be a viable treatment option for locally advanced middle ear LEC not amenable to surgical resection due to expected surgical morbidity. It confers good oncologic outcomes that mimic the response in other head and neck EBV-related lymphoepithelial carcinomas.
The AppNL-G-F mouse retina is a site for preclinical Alzheimer’s disease diagnosis and research
Authors: Vandenabeele Marjan , Veys Lien , Lemmens Sophie , Hadoux Xavier , Gelders Géraldine , Masin Luca , Serneels Lutgarde , Theunis Jan , Saito Takashi , Saido Takaomi C. , Jayapala Murali , De Boever Patrick , De Strooper Bart , Stalmans Ingeborg , van Wijngaarden Peter , Moons Lieve , De Groef Lies
Published: January 2021

In this study, we report the results of a comprehensive phenotyping of the retina of theAppNL-G-Fmouse. We demonstrate that soluble Aβ accumulation is present in the retina of these mice early in life and progresses to Aβ plaque formation by midlife. This rising Aβ burden coincides with local microglia reactivity, astrogliosis, and abnormalities in retinal vein morphology. Electrophysiological recordings revealed signs of neuronal dysfunction yet no overt neurodegeneration was observed and visual performance outcomes were unaffected in theAppNL-G-Fmouse. Furthermore, we show that hyperspectral imaging can be used to quantify retinal Aβ, underscoring its potential as a biomarker for AD diagnosis and monitoring. These findings suggest that theAppNL-G-Fretina mimics the early, preclinical stages of AD, and, together with retinal imaging techniques, offers unique opportunities for drug discovery and fundamental research into preclinical AD.
Type 2 diabetes mellitus-associated transcriptome alterations in cortical neurones and associated neurovascular unit cells in the ageing brain
Authors:   the Cognitive Function and Ageing Study, Bury Joanna J. , Chambers Annabelle , Heath Paul R. , Ince Paul G. , Shaw Pamela J. , Matthews Fiona E. , Brayne Carol , Simpson Julie E. , Wharton Stephen B.
Published: January 2021

Type 2 diabetes mellitus (T2D), characterised by peripheral insulin resistance, is a risk factor for dementia. In addition to its contribution to small and large vessel disease, T2D may directly damage cells of the brain neurovascular unit. In this study, we investigated the transcriptomic changes in cortical neurones, and associated astrocytes and endothelial cells of the neurovascular unit, in the ageing brain. Neurone, astrocyte, and endothelial cell-enriched mRNA, obtained by immuno-laser capture microdissection of temporal cortex (Brodmann area 21/22) from 6 cases with self-reported T2D in the Cognitive Function and Ageing Study neuropathology cohort, and an equal number of age and sex-matched controls, was assessed by microarray analysis. Integrated Molecular Pathway Level Analysis was performed using the Kyoto Encyclopaedia of Genes and Genomes database on significantly differentially expressed genes, defined as P < 0.05 and fold-change ± 1.2. Hub genes identified from Weighted Gene Co-expression Network Analysis were validated in neurones using the NanoString nCounter platform. The expression and cellular localisation of proteins encoded by selected candidate genes were confirmed by immunohistochemistry. 912, 2202, and 1227 genes were significantly differentially expressed between cases with self-reported T2D and controls in neurones, astrocytes, and endothelial cells respectively. Changes in cortical neurones included alterations in insulin and other signalling pathways, cell cycle, cellular senescence, inflammatory mediators, and components of the mitochondrial respiratory electron transport chain. Impaired insulin signalling was shared by neurovascular unit cells with, additionally, apoptotic pathway changes in astrocytes and dysregulation of advanced glycation end-product signalling in endothelial cells. Transcriptomic analysis identified changes in key cellular pathways associated with T2D that may contribute to neuronal damage and dysfunction. These effects on brain cells potentially contribute to a diabetic dementia, and may provide novel approaches for therapeutic intervention.
Dysfunction in nonsense-mediated decay, protein homeostasis, mitochondrial function, and brain connectivity in ALS-FUS mice with cognitive deficits
Authors: Ho Wan Yun , Agrawal Ira , Tyan Sheue-Houy , Sanford Emma , Chang Wei-Tang , Lim Kenneth , Ong Jolynn , Tan Bernice Siu Yan , Moe Aung Aung Kywe , Yu Regina , Wong Peiyan , Tucker-Kellogg Greg , Koo Edward , Chuang Kai-Hsiang , Ling Shuo-Chien
Published: January 2021

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent two ends of the same disease spectrum of adult-onset neurodegenerative diseases that affect the motor and cognitive functions, respectively. Multiple common genetic loci such as fused in sarcoma (FUS) have been identified to play a role in ALS and FTD etiology. Current studies indicate that FUS mutations incur gain-of-toxic functions to drive ALS pathogenesis. However, how the disease-linked mutations of FUS affect cognition remains elusive. Using a mouse model expressing an ALS-linked human FUS mutation (R514G-FUS) that mimics endogenous expression patterns, we found that FUS proteins showed an age-dependent accumulation of FUS proteins despite the downregulation of mouse FUS mRNA by the R514G-FUS protein during aging. Furthermore, these mice developed cognitive deficits accompanied by a reduction in spine density and long-term potentiation (LTP) within the hippocampus. At the physiological expression level, mutant FUS is distributed in the nucleus and cytosol without apparent FUS aggregates or nuclear envelope defects. Unbiased transcriptomic analysis revealed a deregulation of genes that cluster in pathways involved in nonsense-mediated decay, protein homeostasis, and mitochondrial functions. Furthermore, the use of in vivo functional imaging demonstrated widespread reduction in cortical volumes but enhanced functional connectivity between hippocampus, basal ganglia and neocortex in R514G-FUS mice. Hence, our findings suggest that disease-linked mutation in FUS may lead to changes in proteostasis and mitochondrial dysfunction that in turn affect brain structure and connectivity resulting in cognitive deficits.
New missions of a hospital pharmaceutical technology unit during the COVID-19 pandemic
Authors: Garnier Alexandra , Falaschi Ludivine , Bonnabry Pascal , Bouchoud Lucie
Published: January 2021

The pharmaceutical technology unit of the Geneva University Hospitals played a significant role in the fight against COVID-19 through four different missions: (1) providing enough hydroalcoholic solution at the peak of the pandemic; (2) facing supply chain management issues; (3) adapting the workload to the crisis and, above all, (4) managing the human resources necessary to handle these activities.
A review: preprocessing techniques and data augmentation for sentiment analysis
Authors: Duong Huu-Thanh , Nguyen-Thi Tram-Anh
Published: January 2021

In literature, the machine learning-based studies of sentiment analysis are usually supervised learning which must have pre-labeled datasets to be large enough in certain domains. Obviously, this task is tedious, expensive and time-consuming to build, and hard to handle unseen data. This paper has approached semi-supervised learning for Vietnamese sentiment analysis which has limited datasets. We have summarized many preprocessing techniques which were performed to clean and normalize data, negation handling, intensification handling to improve the performances. Moreover, data augmentation techniques, which generate new data from the original data to enrich training data without user intervention, have also been presented. In experiments, we have performed various aspects and obtained competitive results which may motivate the next propositions.
Thinning effects on biomass and element concentrations of roots in adjacent hornbeam and oak stands in Istanbul, Turkey
Authors: Akburak Serdar , Makineci Ender
Published: January 2021

Background

Thinning is a commonly used treatment in forest management which affects the tree root systems. The effects of thinning on element concentrations and seasonal change of roots were evaluated in adjacent oak (Quercus frainetto Ten.) and hornbeam (Carpinus betulus L.) stands according to the different root diameter classes.

Method

Two replicated control and thinning plots (50 m × 50 m) were set for each species (hornbeam and oak). Thinning treatments (November 2010) reduced 50% of the basal area in both oak and hornbeam stands. Roots were assessed by seasonal collection over 2 years (from October 2010 to October 2012). The roots were then sorted into diameter classes of 0–2 mm (fine roots), 2–5 mm (small roots) and > 5 mm (coarse roots). C, N, P, K, Ca, Na, Mg, S, Mn, Fe, Al, Zn, Pb, Ni, Cu and Cd were analyzed.

Results

Except coarse roots, the highest root biomasses were determined in April-2011 in all plots. Fine-root biomass in oak was found significantly higher in control plots. In contrast to the oak, the fine-root biomass in the thinned hornbeam plots was higher than in the controls. The small-root biomass did not significantly differ between the thinned and the control plots in both oak and hornbeam stands. However, the coarse-root biomass showed significant differences between the control (1989 g∙m− 2) and thinned plots (1060 g∙m− 2) in oak, while no difference was detected in hornbeam. The concentrations of C, Al, Pb, Cd, Ni, Zn, Mn, Na, K, Mg and P in the fine roots of oak were significantly higher in the thinned plots. However, the concentration of Pb, Cd and Fe in the fine roots was significantly higher in the thinned plots of hornbeam. Significant differences were observed between the species for all elements in the fine roots except for C, N and P. In particular, elements in the fine roots tended to increase in July in the oak. In the hornbeam, all element concentrations in the fine roots (except C, N, and S) in the thinned plots showed a tendency to increase in April. The concentrations of Pb, Ni, Al, Fe, Cu, Ca, Na, K, Mg and P in the hornbeam control plots increased during the April 2011 period.

Conclusion

The results indicated that thinning effects on temporal changes and concentrations of elements in the roots could be attributed to species-specific characteristics.