bluuebunny/crossref_metadata_2025 huggingface dataset:
Structure-based rational design of an enhanced fluorogen-activating protein for fluorogens based on GFP chromophore
Authors: Goncharuk Marina , Baleeva Nadezhda , Nolde Dmitry , Gavrikov Alexey , Mishin Alexander , Sosorev Andrey , Arseniev Alexander , Goncharuk Sergey , Efremov Roman , Mineev Konstantin , Baranov Mikhail
Published: January 2022

“Fluorescence-Activating and absorption-Shifting Tag” (FAST) is a well-studied fluorogen-activating protein with high brightness and low size, able to activate a wide range of fluorogens. This makes FAST a promising target for both protein and fluorogen optimization. Here, we describe the structure-based rational design of the enhanced FAST mutants, optimized for the N871b fluorogen. Using the spatial structure of the FAST/N871b complex, NMR relaxation analysis, and computer simulations, we identified the mobile regions in the complex and suggested mutations that could stabilize both the protein and the ligand. Two of our mutants appeared brighter than the wild-type FAST, and these mutants provided up to 35% enhancement for several other fluorogens of similar structure, both in vitro and in vivo. Analysis of the mutants by NMR reveals that brighter mutants demonstrate the highest stability and lowest length of intermolecular H-bonds. Computer simulations provide the structural basis for such a stabilization.
Understanding The Workforce That Supports Māori And Pacific Peoples With Type 2 Diabetes To Achieve Better Health Outcomes
Authors: Mullane Tania , Harwood Matire , Warbrick Isaac , Tane Taria , Anderson Anneka
Published: January 2022

Background: Prevalence of Type 2 diabetes mellitus (T2DM) is high among Māori and other Pacific Island peoples in New Zealand. Current health services to address T2DM largely take place in primary healthcare settings and have, overall, failed to address the significant health inequities among Māori and Pacific people with T2DM. Culturally comprehensive T2DM management programmes, aimed at addressing inequities in Māori or Pacific diabetes management and workforce development, are not extensively available in New Zealand. Deliberate strategies to improve cultural safety, such as educating health professionals and fostering culturally safe practices must be priority when funding health services that deliver T2DM prevention programmes. There is a significant workforce of community-based, non-clinical workers in South Auckland delivering diabetes self-management education to Māori and Pacific peoples. These include dietitians, community health workers and, more recently, kai manaaki (KM), but there is little information about these workers and their perspectives, challenges, effectiveness, and success in delivering these services. This study aimed to understand perspectives and characteristics of KM and other community-based, non-clinical health workers, with a focus on how they supported Māori and Pacific Peoples living with T2DM to achieve better outcomes.Methods: This qualitative study was undertaken underpinned by the Tangata Hourua research framework. Focus groups with dietitians, community health workers (CHWs) and KM took place in South Auckland, New Zealand. Thematic analysis of the transcripts was used to identify important key themes. Results: Analysis of focus group meetings identified three themes common across the groups: whakawhanaungatanga (actively building relationships), cultural safety, and cultural alignment. However, there appeared to be two key differences for KM and CHWs, who both preferred a multidisciplinary approach and described their experiences of feeling un/valued in their roles, when compared with dietitians. Generally, all three groups agreed that their roles required good relationships with the people they were working with and an understanding of the contexts in which Māori and Pacific Peoples with T2DM lived. Conclusions: Supporting community based, non-clinical workers to build meaningful and culturally safe relationships with Māori and Pacific people has potential to improve diabetes outcomes.
Timing and quality of antenatal care among adolescent mothers in Luuka district, Uganda
Authors: Kayemba Vincent , Kabagenyi Allen , Ndugga Patricia , Wasswa Ronald , Waiswa Peter
Published: January 2022

Background

Effective Antenatal Care (ANC) is dependent on timely initiation of the first visit and quality care to mitigate risk factors in pregnancy. However, most adolescent mothers attend their first visit later than the recommended time while others do not receive all the required components of care. This study sought to examine the predictors associated with timing of the first ANC visit and receipt of the recommended components of care among adolescent mothers in Luuka district.
Methods

The study was carried out between March and May 2021 among 248 adolescent mothers aged 10-19 years from Luuka district, who were either pregnant or postpartum with infants aged 0-3 months. Data analyses were done using descriptive techniques, Pearson chi-square and Fisher’s exact tests of independence were done at bivariate level and thereafter binary logistic regression.
Results

Findings showed that majority of the adolescent mothers (82%) attended ANC for their most recent pregnancy or birth. Still, only 47% had timely ANC visit while 36% had all the recommended components of care. Having knowledge on dangers signs in pregnancy was a determinant of both receipt of all components of ANC (AOR = 6.57, 95%CI = 1.75 - 24.65) and early timing of the first visit (AOR = 0.35, 95%CI = 0.12 – 0.97). Further, the odds of making the first visit after the first trimester were highest among adolescent mothers who had ever given birth (AOR = 3.67, 95%CI:1.68 - 8.02) and those without independent decisions on health care (AOR = 3.45, 95%CI:1.04 - 11.42).
Conclusion

Knowledge of obstetric pregnancy danger signs, having ever given birth and decision making on health care seeking are pivotal determinants of adolescent mothers’ timing of the first ANC visit and uptake of the recommended components of care. We therefore recommend the need to sensitize adolescent mothers through different channels of media on the benefits of ANC. Also, ensuring accessibility and affordability of these services among health facilities will significantly increase the uptake and early timing of the antenatal care services among adolescent mothers in rural communities.
Transition and Change: Opportunities and Challenges of CHW Policy Reform for Community Health Systems and Vertical Disease Programmes in Liberia
Authors: Zawolo Georgina , Nyaaba Gertrude Nsorma , Nallo Gartee , Kollie Karsor , Thomson Rachael , Raven Joanna , Theobal Sally , Dean Laura
Published: January 2022

Background: Health workforce shortages remain a critical public health challenge. Particularly in low and middle-income countries (LMICs), the re-invigoration of community health workers (CHW) supplement critical health workforce gaps especially during epidemics and pandemics such as Ebola and Coronavirus. National CHW policies can influence CHW motivation and performance. Adaptations to national CHW policies therefore have impacts across the whole health system, particularly for vertical disease programming. Using a case study of Community Drug Distributors (CDDs) working under the Neglected Tropical Disease (NTD) Programme, this paper explores how adaptations to a national CHW policy in Liberia influences health systems and intervention hardware and software factors that impact CHW utilisation, management, and performance in the delivery of vertical disease interventions.Methods: Three qualitative data collection tools were utilized, namely; content analysis of five CHW and NTD program-related policy documents; 25 key informant interviews with facility, county, and national level decision-makers; and 42 life and job histories with CDDs in Liberia. Data were analysed using a thematic framework approach with the coding framework generated in QRS NVivo 11 pro. Transcripts were coded using constant comparison, triangulated, and synthesised with the document review and existing literature for contextual relevance, convergence, and divergence.Results: The health systems hardware dimension shows opportunities and challenges linked to CHW training, motivation, supervision, and logistics and supplies whilst the software dimensions show challenges regarding community engagement and dialogue in CHW programming. Several contextual factors related to the policy adaption potentially facilitate inequities between the various cadres of CHWs, hinder effective supportive supervision and access to medicines, supplies and equipment which shape CDDs motivation and performance which are essential to equitable NTD programme delivery in Liberia. ` Conclusions: This study shows how an adaptation of the CHW policy provides opportunities and challenges for health system hardware and software in varied ways. These have multiple implications for specific intervention hardware and software which provide leveraging opportunities to address gaps and increase CHW motivation and competencies towards better health care delivery and stronger and resilient health systems.
Chromosome-level Genome Assembly Provides Insight Into the Evolution of Chromosomes and the Globin Gene Superfamily in Gymnocypris Eckloni
Authors: Wang Fayan , Wang Lihan , Liu Dan , Gao Qiang , Nie Miaomiao , Zhu Shihai , Chao Yan , Yang Xi , Yang Chaojie , Zhang Cunfang , Yi Rigui , Ni Weilin , Li Guangxin , Chen Qichang , Tian Fei , Zhao Kai , Qi Delin
Published: January 2022

Background: Gymnocypris eckloni is widely distributed in isolated lakes and the upper reaches of the Yellow River and is well adapted to the Qinghai-Tibetan plateau (QTP) aqueous environment. Results: Here, we report the chromosome-level genome of G. eckloni, which is the first genome reported for this highly specialized schizothoracine fish. The final genome was assembled into 918.68 Mb sequences using PacBio long-read and Illumina short-read sequences, including 711 scaffolds with a contig N50 length of 4.19 Mb and a scaffold N50 length of 43.54 Mb. The assembled sequences were further anchored and orientated onto 23 pseudo-chromosomes. In total, 23,157 genes were annotated, representing 94.80% of the total predicted protein-coding genes. We conducted comparative genomic analyses and found that species-specific and rapidly expanding gene families in G. eckloni are mainly involved in Dorso-ventral axis formation, ABC transporters, Peroxisome and Herpes simplex virus 1 infection. The phylogenetic analysis showed that G. eckloni was most closely related to C. carpio with an estimated divergence time of ~34.8 million years ago (Ma), which coincides with the first and second tectonic uplifts of the QTP. We also found that G. eckloni underwent an additional whole-genome duplication (WGD) event (4R) at ~14.2 Ma, which had a significant effect on the evolution of chromosomes and the globin gene superfamily in G. eckloni, thereby facilitating the adaptation of G. eckloni to the plateau water environment.Conclusions: The high-quality genome assembly of G. eckloni will serve as a valuable genomic resource for future research on the evolution and ecology of the schizothoracine fish.
Dactylogyrus Kolodynensis sp. n. (Platyhelminthes: Monogenea) Infecting Gills of Osteobrama Cotio (Hamilton, 1822) (Cypriniformes: Cyprinidae) from India
Authors: Tripathi Amit , Trivedi Amit Kumar , Prakash Sneha
Published: January 2022

Dactylogyrus kolodynensis, a new monogenean parasite species, is described and illustrated from Osteobrama cotio (Cyprinidae) collected from Lawngtlai (Mizoram) and Lucknow (Uttar Pradesh), India using morphological examination and sequencing of partial 28S rRNA gene. The new species is morphologically characterized and distinguished from all congeners by a combination of the following characters: copulatory tube a loose coil of one complete clockwise ring, jaw-shaped accessory piece comprising variable sheathes enclosing and guiding the copulatory tube, and sclerotized vaginal tube, with a terminal flower-bud-shaped vaginal pore. The molecular analyses of specimens of D. kolodynensis collected from the two different localities using 28S rRNA gene showed identical genotype that did not match any of the known sequences in GenBank, confirming our initial morphological identification. Dactylogyrus cotius, a sympatric species on the gills of O. cotio, is regarded as a species inquirenda because of its poor description. This is the first report of a monogenean species from Mizoram, in northeast India, bringing the total number of Dactylogyrus species in India to 57.
Arbuscular Mycorrhiza Alters The Nutritional Requirements In Salvia Miltiorrhiza And Low Nitrogen Enhances The Mycorrhizal Efficiency
Authors: Pu Chunjuan , Yang Guang , Li Pengying , Ge Yang , Garran Thomas Avery , Zhou Xiuteng , Shen Ye , Zheng Han , Chen Meilan , Huang Luqi
Published: January 2022

Salvia miltiorrhiza Bunge (danshen in Chinese) is one of the most important medicinal cash crops in China. Previously, we showed that arbuscular mycorrhizal fungi (AMF) can promote S. miltiorrhiza growth and the accumulation of bioactive compounds. Fertilization may affect mycorrhizal efficiency, and appropriate doses of phosphate (P) and nitrogen (N) fertilizers are key factors for obtaining mycorrhizal benefits. However, the optimal fertilization amount for mycorrhizal S. miltiorrhiza remains unclear. In this study, we studied the effects of AMF on the growth and bioactive compounds of S. miltiorrhiza under different doses (low, medium, and high) of P and N fertilizer. The results showed that the mycorrhizal growth response (MGR) and mycorrhizal response of bioactive compounds (MBC) decreased gradually with increasing P addition. Application of a low (N25) dose of N fertilizer significantly increased the MGR of mycorrhizal S. miltiorrhiza, and a medium (N50) dose of N fertilizer significantly increased the MBC of phenolic acids, but decreased the MBC of tanshinones in mycorrhizal S. miltiorrhiza. Our results also showed that the existence of arbuscular mycorrhiza changes nutrient requirement pattern of S. miltiorrhiza. P is the limiting nutrient of non-mycorrhizal plants whereas N is the limiting nutrient of mycorrhizal plants.
Exocomets Size Distribution In The β Pictoris Planetary System
Authors: des Etangs Alain Lecavelier , Cros Lucie , Hébrard Guillaume , Martioli Eder , Duquesnoy Marc , Kenworthy Matthew , Kiefer Flavien , Lacour Sylvestre , Lagrange Anne-Marie , Meunier Nadège , Vidal-Madjar Alfred
Published: January 2022

The star β Pictoris harbors a young planetary system, which is characterized by the presence of a gaseous and dusty debris disk, at least two massive planets and many minor bodies. For more than thirty years, exocomets transiting the star have been detected using spectroscopy, probing the gaseous part of the cometary comas and tails. The detection of the dusty component of the tails can be performed through photometric observations of the transits. Since 2018, the Transiting Exoplanet Survey Satellite has observed β Pic for a total of 156 days. Here we report an analysis of the TESS photometric data set with the identification of a total of 30 transits of exocomets. Our statistical analysis shows that the number of transiting exocomet events (N) as a function of the absorption depth (AD) in the light curve follows a power law in the form dN(AD) ∝ AD−α , where α = 2.3 ± 0.4. This distribution of absorption depth leads to a differential comet size distribution proportional to R−γ , where γ = 3.6 ± 0.8, showing a striking similarity to the size distribution of comets in the Solar system and the distribution of a collisionally relaxed population (γD = 3.5).
Synthesis and Evaluation of Naphthalene Derivatives as Potent STAT3 Inhibitors and Agents Against Triple-Negative Breast Cancer Growth and Metastasis
Authors: Yang Zhengyan , Xu Hongyun , Yang Yupo , Duan Chaoqun , Zhang Pai , Zhou Yuan , Wang Xin , Li Pan , Wang Yang , Fu Kai , Shen Yonghong , Xu Marvin Xuejun
Published: January 2022

Purpose Signal transducer and activator of transcription 3 (STAT3) has been reported to be hyper-activated in triple-negative breast cancers (TNBCs) and predicts poor outcomes. However, no drugs targeting STAT3 have been marketed. To develop STAT3 inhibitors for the treatment of TNBC, we synthesized and evaluated a new series of naphthalene derivatives. Methods A new series of compounds with the scaffold of Selective Estrogen Receptor Modulator (SERM) and an amino group were designed and screened on the basis of the structure−activity relationship by MTT assay. The binding activity of SMY002 to STAT3 was predicted and validated by docking and SPR. The STAT3 signaling target and anti-cancer effect of SMY002 were evaluated by 3 three TNBC cell lines and the mice transplanted tumor model.Results Among the compounds, SMY002 (2a) displayed the most potent activity, which could directly interact with STAT3 SH2-domain, and strongly inhibit phosphorylation, dimerization, nuclear distribution, transcriptional activity, and target genes expression of STAT3. Furthermore, SMY002 markedly suppressed migration, invasion, survival, growth, and metastasis of TNBC cells in vitro and in vivo via down-regulating the expression of Cyclin D1 and MMP9.Conclusion The new compound SMY002 holds the potential of being developed into STAT3 inhibitory tools and TNBC treatment agents.
A Novel Mutation of KCNJ1 Identified in an Affected Child with Nephrolithiasis
Authors: Wu Qinghua , Yang Saisai , Shi Huirong , Lou Chihhong , Ren Shumin , Jiao Zhihui , Wang Cong , Kong Xiangdong
Published: January 2022

Nephrolithiasis is not common in children, but the incidence is gradually increased in these years. Urinary tract malformations, urinary infection, dietary habits, geographic region and genetic factor are involved in the etiology of nephrolithiasis. For the affected child, it is especially important to elucidate the etiology, which may provide an accurate diagnosis, a personalized therapy and effective follow-up strategy. Here to seek the etiology of a ten-year old boy incidentally found with nephrolithiasis, next generation sequencing (NGS) including a panel with 248 genes involved in hereditary kidney diseases was performed for the boy and identified two mutations of KCNJ1, c.89G>A (p.C30Y) and c.65G>T (p.R22M), and the later was a novel missense mutation originated from his father. The child was confirmed with type II Bartter syndrome (BS) caused by KCNJ1 mutations. Our study suggests that BS may be difficult to get diagnosed at early stage based on clinical manifestations or biochemical laboratory tests, and NGS is an efficient way to determine the etiology and provide further treatment and guide fertility counselling for the affected family.
A histone modification-based synthetic circuit to engineer temporal gene expression in Arabidopsis floral meristems
Authors: Pelayo Margaret , Sawada Haruka , Matsushita Kasumi , He Zemiao , Looi Liang Sheng , Katagiri Naoya , Yamaguchi Nobutoshi , Ito Toshiro
Published: January 2022

The termination of floral meristems is regulated by the MADS domain transcription factor AGAMOUS (AG) by passively diluting the H3K27me3 mark along the KNUCKLES (KNU) coding sequence. How many other downstream genes are similarly regulated by this intrinsic epigenetic timer and whether it can be harnessed for engineering synthetic circuits are unknown. Here, we describe a biotimer gene regulatory network downstream of AG and manipulate the timing of KNU expression through a synthetic system. We manipulated temporal gene expression using the del region from the KNU coding sequence, which is decorated by H3K27me3-marked nucleosomes. Increasing the number of del copies delayed and reduced KNU expression in a PRC2- and cell cycle-dependent manner. We propose that PRC2 deposits H3K27me3, while cell divisions dilute H3K27me3 accumulation on the extended KNU coding sequence. Our results shed light on temporal transitions governing flower development and provide a novel tool for tunable gene expression.
Finite Time Adaptive Smooth Non Linear Sliding Mode Control for Second Order Dynamic Systems
Authors: González-Prieto José Antonio
Published: January 2022

In this paper, a feedback control law that employs an adaptive smooth nonlinear approximation of the Super-Twisting ( STW ) algorithm is presented in order to generate a smooth control law capable of regulating in finite time a second-order system that is affected by unknown disturbances and uncertainties. A nonlinear sliding surface is created in order to set the desired dynamics of the response, so that the control law is proposed to establish global properties of stability for unperturbed and perturbed systems. More specifically, the method entails determining parameters that eliminate chattering in noise-free models by means of a simple cut-off frequency design parameter approach. Therefore, the approach is characterized by its simplicity and robustness. A second order mechanical system is used to demonstrate the effectiveness of the proposed approach.
Longitudinal Mapping of White Matter Tractography Changes in Huntington’s Disease: The IMAGE-HD Study.
Authors: Tan Brendan , Shishegar Rosita , Oldham Stuart , Fornito Alex , Poudel Govinda , Georgiou-Karistianis Nellie
Published: January 2022

The striatum is the principal site of disease pathology in Huntington’s disease and contains neural connections to numerous cortical brain regions. Studies examining abnormalities to neural connections find that white matter integrity is compromised in HD; however, further regional, and longitudinal investigation is required. This paper is the first longitudinal investigation into region-based white-matter integrity changes in Huntington’s Disease. The aim of this study was to better understand how disease progression impacts white matter tracts connecting the striatum to the prefrontal and motor cortical regions in HD. We used existing neuroimaging data from IMAGE-HD, comprised of 25 pre-symptomatic, 27 symptomatic, and 25 healthy controls at three separate time points (baseline, 18-months, 30-months). Fractional anisotropy, axial diffusivity and radial diffusivity were derived as measures of white matter microstructure. The anatomical regions of interest were identified using the Desikan-Killiany brain atlas. A Group by Time repeated measures ANCOVA was conducted for each tract of interest and for each measure. We found significantly lower fractional anisotropy and significantly higher radial diffusivity in the symptomatic group , compared to both the pre-symptomatic group and controls (the latter two groups did not differ from each other), in the rostral middle frontal and superior frontal tracts; as well as significantly higher axial diffusivity in the rostral middle tracts only. We did not find a Group by Time interaction for any of the white matter integrity measures. These findings demonstrate that whilst the microstructure of white matter tracts, extending from the striatum to these regions of interest, are compromised during the symptomatic stages of Huntington’s disease, 36-month follow-up did not show progressive changes in these measures. Additionally, no correlations were found between clinical measures and tractography changes, indicating further investigations into the relationship between tractography changes and clinical symptoms in Huntington’s disease are required.
Embolization of Arteriovenous Malformations in Floor of Mouth with Ethanol and Coil-Assisted Dominant Outflow Vein Occlusion
Authors: Su Lixin , Wang Deming , Zheng Lianzhou , Li Xiao , Fan Xindong , Yang Xitao
Published: January 2022

Purpose
To evaluate the outcomes and safety of embolization of the arteriovenous malformations (AVMs) in the floor of the mouth with ethanol combined with coil-assisted dominant outflow vein (DOV) occlusion.
Materials and methods
Between January 2017 and June 2018, 10 consecutive patients with AVMs in the floor of the mouth and DOVs who underwent ethanol embolization combined with DOV occlusion were enrolled. All patients completed the course of clinical follow-up (range: 14–37 months; mean: 24.8 months). Indications, techniques, complications, and outcomes were reviewed.
Results
The patients underwent 24 ethanol embolization procedures (range: 1–4; mean, 1.9) with 22 detachable coils and 139 nester coils. 5 patients (50%) exhibited complete response, and the 5 (50%) exhibited partial response. The minor complications, including mucosal blistering and ulcers, occurred in 3 patients (30%), but with spontaneous recovery. 3 patients (30%) had coil exposure heal with minor debridement. No major complications were observed during the study.
Conclusion
Ethanol embolization combined with coil-assisted DOV occlusion has the potential to treat the AVMs in floor of mouth with acceptable risk of complications.
MilR3, a Unique SARP Family Pleiotropic Regulator in Streptomyces Bingchenggensis
Authors: Yan Yu-Si , Yang Yun-Qi , Zou Li-Sha , Zhang Ling , Xia Hai-Yang
Published: January 2022

Streptomyces bingchenggensis is the main industrial producer of milbemycins, which are a group of 16-membered macrocylic lactones with excellent acaricidal, insecticidal and anthelmintic activities. In past decades, scientists tried a lot to solve its low productivity. But less understanding the regulatory network of milbemycin biosynthesis limited the generation of high producing strains with regulatory rewiring approach. SARPs（Streptomyces Antibiotic Regulatory Proteins）family regulators are widely distributed and play key roles in regulating antibiotics production in actinobacteria. In this paper, MilR3 (encoded by sbi_06842) has been screened out for significantly affecting milbemycin production from all the 19 putative SARP family regulators in S. bingchenggensis with the DNase-deactivated Cpf1-based integrative CRISPRi system. Interestingly, milR3 is about 7 Mb away from milbemycin biosynthetic gene cluster and adjacent to a putative type II PKS （the core minimal PKS encoding genes are sbi_06843, sbi_06844 and sbi_06845）gene cluster, which was proved to be responsible for producing a yellow pigment. The quantitative real-time PCR (qRT-PCR) analysis proved that MilR3 positively affected the transcription of milR, milA1, milA2, milA4, milF, milR3 and sbi_06844 in both clusters. Unlike previous “small” SARP family regulators played pathway specific roles, MilR3 was probably a unique SARP family regulator and played a pleotropic role. MilR3 was an upper-level regulator in MilR3-MilR cascade. This study firstly illustrated the co-regulatory role of this unique SARP regulator. This greatly enrich our understanding of SARPs and lay a solid foundation for milbemycin yield enhancement in the near future.
CT-Based Skeletal Muscle Loss for Predicting Poor Survival in Patients With Hepatocellular Carcinoma Experiencing Curative Hepatectomy Plus Adjuvant Transarterial Chemoembolization:a Preliminary Retrospective Study
Authors: Yang Siwei , Zhang Zhiyuan , Su Tianhao , Yu Jianan , Cao Shasha , Wang Haochen , Jin Long
Published: January 2022

Background To evaluate the prognostic value of skeletal muscle index (SMI) and its change in patients with hepatocellular carcinoma (HCC) experiencing curative hepatectomy plus adjuvant transarterial chemoembolization (TACE). Methods and Methods A total of 62 patients with HCC who underwent adjuvant TACE after curative hepatectomy were analysed retrospectively. Skeletal muscle area at the third lumbar level was quantitated using computed tomography images and was normalized for height squared to obtain skeletal muscle index (SMI). Skeletal muscle loss (SML) over six months was computed with two SMIs before and after hepatectomy plus adjuvant TACE. Correlation analyses were preformed to investigate factors associated with SML. The curves of cause-specific survival (CSS) were analysed using the Kaplan-Meier method. A Cox proportional hazards model was used to assess prognostic factors. Results Low SMI was diagnosed in 23(37.1%) patients preoperatively. The median SML standardized by 6 months was -1.6% in the entire cohort. Liver cirrhosis and microvascular invasion correlated negatively with SML respectively (r=-0.320, P=0.002; r=-0.243, P=0.021). Higher SML (<-2.42%) predicted a significant reduction in CSS (P=0.001), whereas low SMI did not(P=0.687). Following the multivariate analysis for CSS, AFP> 400 ng/ml (HR, 5.643; 95%CI, 3.608-17.833; P<0.001) and SML<-2.42% (HR, 6.586; 95%CI, 3.610-22.210; P<0.001) were independent predictors for poor CSS.Conclusions Skeletal muscle loss during hepatectomy plus adjuvant TACE was remarkable. Higher SML was an independent risk factor for CSS in patients with HCC, especially those with liver cirrhosis.
Low Transcriptomic of PTPRCv1 and CD3E Is an Independent Predictor of Mortality in HIV and Tuberculosis Co–infected Patient
Authors: Gebremicael Gebremedhin , Gebreegziaxier Atsbeha , Kassa Desta
Published: January 2022

Background: Assessing immunological profiles from HIV-TB co-infection is essential to predict mortality, to facilitate the development of effective assays, the discovery of novel therapeutic targets and to conduct new interventions appropriately.Methods: Expression levels of 105 immune-related genes were measured at baseline of enrolment from 9 death HIV and TB coinfected study participants during follow-up and 18 survived groups for 2 years and matched controls, using focused gene expression profiling by dual-color Reverse-Transcription Multiplex Ligation-dependent Probe Amplification assay. Gene expression levels were also measured at six months and 18th month follow-up.Results: Eleven of the 105 selected genes were differentially expressed between death individuals and survivor matched controls. IL4δ2 was significantly higher expressed in death groups than survivor matched controls, whereas CD3E, IL7R, PTPRCv1, CCL4, GNLY, BCL2, CCL5, NOD1, TLR3 and NLRP13 had significantly lower expression levels in death groups compared to survivor matched controls. The expression of PTPRCv1, CD3E, CCL5, IL7R, NOD1, IL4δ2 and GNLY at baseline could accurately predict the mortality from TB-HIV co-infection.Conclusions: The expression of PTPRCv1, CD3E, CCL5 and IL7R host genes in peripheral blood of patients with TB-HIV coinfected can potentially be used as predictor of mortality in Ethiopian setting. Anti-TB treatment might be less likely to restore gene expression in the level expression of death groups. Therefore, other new therapeutic that can restore these gene (PTPRCv1, CD3E, IL7R and CCL5) in the death groups at baseline might be needed to save lives.
Are Travel Bans the Answer to Stopping the Spread of COVID-19 Variants? Lessons from a Multi-Country SIR Model
Authors: Docquier Frédéric , Golenvaux Nicolas , Schaus Pierre
Published: January 2022

Background: Detections of mutations of the SARS-CoV-2 virus gave rise to new packages of interventions. Among them, international travel restrictions have been one of the fastest and most visible responses to limit the spread of the variants. While inducing large economic losses, the epidemiological consequences of such travel restrictions are highly uncertain. They may be poorly effective when the new highly transmissible strain of the virus already circulates in many regions. Assessing the effectiveness of travel bans is difficult given the paucity of data on daily cross-border mobility and on existing variant circulation. The question is topical and timely as the new omicron variant -- classified as a variant of concern by WHO -- has been detected in Southern Africa, and perceived as (potentially) more contagious than previous strains. In this study, we develop a multi-country compartmental model of the SIR type. We use it to simulate the spread of a new variant across European countries, and to assess the effectiveness of unilateral and multilateral travel bans. Results: Multilateral travel bans do not buy much time, by increasing the time until the infection curve peaks by a few weeks at best. This can be achieved with drastic travel bans only, and this fails to stop the propagation when the virus is already circulating in the country, or in regions not included in the travel bans. Conclusion: Given their huge economic and freedom-killing consequences, travel bans have negligible effects on the timing and severity of the infection response. Managing new waves of COVID-19 with local sanitary measures applicable to cross-border movers is the most effective option. It induces better epidemiological outcomes and smaller economic cost for all parties concerned.
PALB2 Correlates with Adverse Prognosis and Promotes Tumor Progression in Chordoma
Authors: Xiong Yujia , Li Mingxuan , Sheng Yutao , Ma Tianshun , Bai Jiwei , Zhang yazhuo
Published: January 2022

Objective:This study aimed to study the role of PALB2 on the prognosis of skull base chordoma patients and the proliferation, migration, and invasion of chordoma cells. Methods:187 patients with primary skull base chordoma were involved in the study. Immunohistochemical analysis was used to measure the PALB2protein expression. Kaplan-Meier analysis, univariate and multivariate Cox analysis were used to evaluate the impact of PALB2 on patient prognosis. A nomogram was established for predicting the progressionfree survival of chordoma patients. Cell counting kit-8,colony formation, transwellmigration, and invasionassays were used to assess the proliferation, migration, and invasion of chordoma cells with PALB2 knockdown. TIMER 2.0 was used to explore the expression and prognostic role of PALB2 in cancers.Results:High PALB2 expression indicated anadverse prognosis in chordoma. A nomogram involved PALB2,degree of resection, pathology, and Al-mefty classification could accurately predict the progressionfree survival of chordoma patients. The proliferation, migration, and invasion of chordoma cells significantly decreased after PALB2 knockdown. Additionally, PALB2 showed high expression in various cancers and was associated with a poor prognosis.Conclusion: In summary, our results reveal that high PALB2 expression indicates a poor prognosis of chordoma patients and promotes the malignant phenotypes of chordoma cells in vitro.
DUB1 Suppresses Hippo Signaling Via Modulating TAZ Protein in Gastric Cancer
Authors: Wang Dehai , Li Zhongbo , Li Xin , Yan Cheng , Yang Huijie , Zhuang Ting , Wang Xiao , Zang Yifeng , Liu Ziping , Wang Tianshi , Jia Ruixia , Su Peng , Zhu Jian , Ding Yinlu
Published: January 2022

Background

The Hippo pathway functions as a tumor-suppressor pathway in human cancers, while the dys-function of Hippo pathway is frequently observed in malignancies. Although the YAP/TAZ activity is tightly controlled by the phosphorylation cascade of MST-LATS-YAP/TAZ axis, it is still unclear why YAP/TAZ protein is activated in human cancers, even Hippo pathway is still active. Besides phosphorylation, recent studies implicate that several post-translational modifications also play critical roles in modulating TAZ function, including ubiquitination.
Methods

We work on the ER alpha positive breast cancer cell lines and performed western blots, real-time PCR, immuno-precipitation assay, in vitro ubiquitin assay and xenograft mice studies
Results

Here, by a DUB (Deubiquitinases) siRNA screening library, we discovered DUB1 as a critical modulator to facilitate gastric cancer stemness and progression, which deubiquitinated and activated TAZ protein. We also identified DUB1 was elevated in gastric cancer, which correlated with TAZ activation and poor survival. DUB1 associated with TAZ protein and deubiquitinated TAZ at several lysine sites, which subsequently stabilized and facilitated TAZ function.
Conclusions

Our study revealed a novel deubiquitinase of Hippo/TAZ axis and one possible therapeutic target for Hippo-driven gastric cancer.
Novel self-assembled isonicotinic acid derivative and zinc porphyrin dyads and applications in dye sensitized solar cells
Authors: Wu Yu , Wang Qiumin , Wang Fang , Cheng Mei , Liu Jiacheng , Li Renzhi
Published: January 2022

A new self-assemblies based on double-deck dyes ZnTPP-Wi (i=1-3) were synthesized and applied in dye-sensitized solar cells (DSSCs). Anchoring molecules (Wi i=1-3) consisting of phenyl carboxyl acid and cyanoacetic acid group. Capping layer dyes ZnTPP with anchoring molecules formed dyads by the coordination bonds of Zn-to-ligand self-assemblies solar cells devices. We herein report a consisting acylamide and cyanoacetic acid group W3 as an anchoring molecule for the axial coordination with upper zinc porphyrin ZnTPP. W3 was synthesized by introducing acylamide and cyanoacetic acid groups may inhibit adverse dye aggregation and improving electrons are effectively injected into the TiO2 semiconductor surface. Thus, W3 anchoring molecules can be used to fabricate efficient solar cells with ZnTPP porohyrin dye, achieving good photoelectric performance, indicative of their general applicability in fabricating good-performance DSSCs. The assembled modes were also verified by transmission electron microscopy (TEM). The photoelectrochemical efficiencies for dye ZnTPP-W3 are best than those of self-assembly dyes prevailingly ascribed to larger Jsc and Voc.
Mst1-Nrf2 regulates myocardial injury in type 2 diabetic mice through autophagy
Authors: Wang Jun , Li Guangwei , Wang Na , Wang Lulu , Jin Li , Xiao Wei
Published: January 2022

Purpose This paper presents the effect of Mst1-Nrf2 on myocardial injury in type 2 diabetic mice through autophagy. Method C57BL/6N wild-type mice, Mst1 knockout mice and Mst1 knockout mice interfered by Keap1-Nrf2 pathway inhibitors are divided into wild group, Mst1 group, Mst1-Nrf2 group, diabetic cardiomyopathy group (DCM), DCM+Mst1 group and DCM+ Mst1-Nrf2 group. Each group contains 5 mice. Mice in DCM group, DCM+Mst1 group and DCM+Mst1-Nrf2 group are given high-glucose and high-fat diet for 4 weeks, then intraperitoneally injected 40mg/kg streptozotocin(STZ). Meanwhile, high-glucose and high-fat diet is continued for 8 weeks. Body weight and fasting blood glucose are measured every week. Mice in Mst1-Nrf2 group and mice in DCM+Mst1-Nrf2 group are given interference of Keap1-Nrf2 pathway inhibitors, and intraperitoneally injected for 4 weeks at a dose of 5mmol/L. Results After 8 weeks of STZ injection, the body weight of mice in DCM+Mst1 group and mice in DCM+ Mst1-Nrf2 group increases and fasting blood glucose level decreases, the differences are statistically significant (P<0.01). Compared with the wild group, the fasting glucose level of mice in Mst1 group and Mst1-Nrf2 group decreases after 8 weeks (P<0.01). Compared with the wild group, the degree of myocardial fibrosis in Mst1 group and Mst1-Nrf2 group is significantly reduced, while the level of myocardial fibrosis in DCM group is significantly increased (P < 0.01). After 8 weeks of STZ injection, the degree of myocardial fibrosis in DCM+Mst1 group and DCM+ Mst1-Nrf2 group is significantly reduced. Compared with the wild group, the expression of myocardial Beclin1 protein in Mst1 group and Mst1-Nrf2 group is significantly increased (P < 0.01); Compared with DCM group, myocardial Beclin1 protein expression is significantly increased in DCM+Mst1 group and DCM+Mst1-Nrf2 group(P< 0.01). Compared with the wild group, the expression of p62 protein in myocardium of Mst1 group and Mst1-Nrf2 group is significantly decreased (P < 0.01). Compared with DCM group, the expression of p62 protein in myocardium of DCM+Mst1 group and DCM+Mst1-Nrf2 group is decreased significantly (P< 0.01). Compared with the wild group, myocardial Nrf2 protein expression in Mst1 group and Mst1-Nrf2 group is significantly increased (P < 0.01). Compared with DCM group, myocardial Nrf2 protein expression of mice in DCM+Mst1 group and DCM+ Mst1-Nrf2 group is significantly increased (P < 0.01). Conclusion Mst1-Nrf2 promotes autophagy in type 2 diabetic mice and inhibits the progression of diabetic cardiomyopathy.
Oxygen regulates ILC3 antigen presentation potential and pregnancy-related hormone actions
Authors: Einenkel Rebekka , Ehrhardt Jens , Zygmunt Marek , Muzzio Damián Oscar
Published: January 2022

Early pregnancy is marked by placentation and embryogenesis, which take place under physiological low oxygen concentrations. This oxygen condition is crucial for many aspects of placentation, trophoblast function, vascularization and immune function. Recently, a new family of innate lymphoid cells has been found to be expressed at the fetomaternal interface. Among these, type 3 innate lymphoid cells (ILC3) are important antigen presenting cells in the context of MHCII. The expression of MHCII on ILC3s during pregnancy is reduced. We tested the hypothesis that low oxygen concentrations reduce the potential of ILC3s to present antigens promoting fetal tolerance.Using an in vitro approach, NCR+ ILC3s generated from cord blood stem cell precursors were incubated under different O2 concentrations in the presence or absence of the pregnancy-related hormones hCG and TGF‑β1. The expression of MHCII, accessory molecules and an activation marker were assessed by flow cytometry. We observed that 1 % O2 reduced the expression of the MHCII molecule HLA-DR as compared to 21 % O2 and modulated the relative effects of hCG and TGF‑β1. Our data indicate that low oxygen concentrations reduce the antigen presentation potential of NCR+ ILC3s and suggest that it may promote fetal tolerance during the first trimester of pregnancy.
Lead federated neuromorphic learning for edge artificial intelligence
Authors: Yang Helin , Lam Kwok-Yan , Xiao Liang , Xiong Zehui , Hu Hao , Niyato Dusit , Poor Vincent
Published: January 2022

Despite the great potential of edge artificial intelligence (AI) which is the convergence of edge computing and AI, it acquires sufficiently large/diverse datasets and requires high energy consumption for model training on resource-constrained edge devices, hence hindering the application of edge AI at edge devices. This paper proposes a lead federated neuromorphic learning (LFNL) technique, which is a decentralized energy-efficient brain-inspired computing method, enabling edge devices to collaboratively train a global model while preserving privacy. Experimental results validate that LFNL substantially reduces the data traffic by >3.5× and computational latency by >2.0× compared to centralized learning, with a comparable classification accuracy, as well as significantly outperforms local learning with uneven dataset distribution among edge devices. Meanwhile, LFNL significantly reduces the energy consumption by >4.5× compared to standard federated learning with a slight accuracy loss up to 1.5%. Therefore, the newly proposed LFNL can facilitate the development of brain-inspired computing and edge AI.
Tuberculosis Treatment Outcomes and Associated Factors Among Tuberculosis Patients in Bule Hora General Hospital, Southern Ethiopia, 2021: Retrospective Cross-sectional Study
Authors: Galgalo Dawit
Published: January 2022

Background

In Ethiopia tuberculosis is the leading causes of morbidity, the incidence of all forms of TB in the Ethiopia was 379/100000 population which is the second on the Africa continent. There are high discrepancies in the result of treatment outcome being reported from the different region of the country with frequent poor treatment outcomes particularly from the southern Ethiopia. Thus, this study aims to assess tuberculosis treatment outcomes and associated factors among tuberculosis patients in Bule Hora general hospital, southern Ethiopia
Methods

Facility based retrospective cross-sectional document review of 349 patients was conducted to assess the TB treatment outcome and associated factors for TB patients’ document registration. Data was entered into the computer using Epi-data software version 3.2 and exported to SPSS software version 22 for analysis. Bivariate and multivariate analysis with 95% confidence intervals were employed to infer associations between the independent and dependent variables.
Result

The documents of 349 tuberculosis patients were reviewed. Among this patients, 87.9% were successfully treated whereas 12.1% of the patients were unsuccessfully treated. From this, 53.4% and 34.5% patients were cured and completed the treatment, respectively, whereas 3.7%, 5.8%, and 2.6% patients were died, treatment failure, and defaulted, respectively during the follow-up. The tuberculosis patients who were screed positive for HIV/AIDS were 86% less likely to had a successful TB treatment outcome than HIV/AID negative patients.
Conclusion

The TB treatment outcome for the present study was 87.9%, which was lower than national achievement in 2017 (96%) and global target (>=90%) which required improvement. The higher unsuccessful TB treatment outcomes among HIV positive patients suggests the need to strengthen adherence education and supervision.
Functionalization of Two-Dimensional Coordination Polymer in Small Organic Matters Removal from Organic Wastewater
Authors: Fauzi Billy Oktora Abdilah , Kondo Mitsuru , Elzagheid Mohamed I. , Rhyman Lydia , Ramasami Ponnadurai
Published: January 2022

Multicobalt(II) two-dimensional layer coordination polymer {[Co(bitbu-OMe)2(NCS)2]·2MeOH}n (1) was synthesized using a bis-imidazole ligand having a steric hindrance, tert-butyl, and one methoxy group expressed by bitbu-OMe (bitbu-OMe = 1,1’-[(5-tert-butyl-2-methoxybenzene-1,3-diyl)dimethanediyl]bis(1H-imidazole). Since there are two methanol molecules trapped inside each void within 1, the investigation of small organic matters removal from organic wastewater was conducted in order to reveal its ability in the purification process. The research findings indicate that 1 has the ability to capture methanol, acetone, acetonitrile, and tetrahydrofuran in organic wastewater with removal ratios of 29.17%, 63.22%, 42.77%, and 21.24%, respectively.
Expression and prognostic value of CD80 and CD86 in the tumor microenvironment of newly diagnosed glioblastoma
Authors: Ahmed Mohammed , Hernández-Verdin Isaias , Verreault Maite , Bielle Franck , Lerond Julie , Alentorn Agusti , Sanson Marc , Idbaih Ahmed
Published: January 2022

Background Strategies to modulate the tumor microenvironment (TME) have opened new therapeutic avenues with dramatic yet heterogeneous intertumoral efficacy in multiple cancers, including glioblastomas. Therefore, investigating molecular actors of TME may help understand the interactions between tumor cells and TME. Immune checkpoint proteins such as a Cluster of Differentiation 80 (CD80) and CD86 are expressed on the surface of tumor cells and infiltrative tumor lymphocytes. However, their expression and prognostic value in glioblastoma (GBM) microenvironment is still unclear. Methods In this study, we investigated, in a retrospective local discovery cohort and a validation TCGA dataset, expression of CD80 and CD86 at mRNA level and their prognostic significance in response to standard of care. Furthermore, CD80 and CD86 at the protein level were investigated in the discovery cohort. Results Both CD80 and CD86 are expressed heterogeneously in the TME at mRNA and protein levels. In a univariate analysis, the mRNA expression of CD80 and CD86 was not significantly correlated with OS in both local OncoNeuroTech dataset (ONT) and TCGA datasets. CD80 and CD86 mRNA high expression was significantly associated with shorter PFS (p<0.05). These findings were validated using the TCGA cohort; higher CD80 and CD86 expressions were correlated with shorter PFS (p<0.05). In multivariate analysis, CD86 mRNA expression was an independent prognostic factor for PFS in the TCGA dataset only (p<0.05). Conclusion CD86 could be used as a potential biomarker for the prognosis of GBM patients treated with immunotherapy however additional studies are needed to validate these findings.