bluuebunny/crossref_metadata_2025 huggingface dataset:
Kiss1/Gpr54 Prevents Bone Loss through Src Dephosphorylation
by Dusp18 in Osteoclasts
Authors: Li Zhenxi , Yang Xinghai , Jiao Jian , Wu Zhipeng , Wu Zhixiang , Xu Shengzhao , Li Wenjun , Ma Guoli , Wu Pengfei , Qian Ming , Wei Haifeng , Zhao Jian , Chen Yihua , Zhang Han-kun , Cheng Yiyun , Siwko Stefan , Lian Gewei , Inuzuka Hiroyuki , Wei Wenyi , Song Gaojie , Luo Jian , Liu Mingyao , Xiao Jianru
Published: December 2021

Osteoclasts were over-activated as we age, which leads to bone loss. Src-deficient mice lead to only one phenotype -severe osteopetrosis due to functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCR) have been targets for ∼35% of approved drugs. However, how Src kinase activity is negatively regulated by GPCRs remains largely elusive. Herein we report that Src is dephosphorylated at Tyr 416 by Dusp18 upon GPR54 activation by its natural ligand Kp-10. Mechanically, both active Src and the Dusp18 phosphatase are recruited by GPR54 through the proline/arginine-rich motif (PR motif) in the C terminus, which is dependent on the Gαq signal pathway. As such, Kiss1, Gpr54, Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss. Accordingly, Kp-10 abrogated bone loss by suppressing osteoclasts activity in vivo. Therefore, Kiss1/Gpr54 is a promising therapeutic strategy governing bone resorption through Src dephosphorylation by Dusp18.
Inositol Hexakisphosphate Primes Syndapin I/PACSIN 1 Activation In Endocytosis
Authors: Shi Yue , Zhao Kaixuan , Yang Guang , Yu Jia , Li Yuxin , Kessels Michael M. , Yu Lina , Qualmann Britta , Berggren Per-Olof , Yang Shao-Nian
Published: December 2021

Endocytosis is controlled by a well-orchestrated molecular machinery, where the individual players as well as their precise interactions are not fully understood. We now show that syndapin I/PACSIN 1 is expressed in pancreatic β cells and that its knockdown abrogates β cell endocytosis leading to disturbed plasma membrane protein homeostasis, as exemplified by an elevated density of L-type Ca2+ channels. Intriguingly, inositol hexakisphosphate (InsP6) activates casein kinase 2 (CK2) phosphorylating syndapin I/PACSIN 1, promoting interactions between syndapin I/PACSIN 1 and neural Wiskott-Aldrich syndrome protein (N-WASP) thereby driving β cell endocytosis. Dominant-negative interference with endogenous syndapin I/PACSIN 1 protein complexes, by overexpression of the syndapin I/PACSIN 1 SH3 domain, decreases InsP6-stimulated endocytosis. InsP6 thus promotes syndapin I/PACSIN 1 priming by CK2-dependent phosphorylation, which endows the syndapin I/PACSIN 1 SH3 domain with the capability to interact with the endocytic machinery and thereby initiate endocytosis, as exemplified in β cells.
5-Fluorouracil And Curcumin With Pectin Coating As a Treatment Regimen For Titanium Dioxide Induced Colon Cancer Model
Authors: Karthika Chenmala , Sureshkumar Raman , Sajini Deepak Vasudevan Vasudevan , Ash Gulam Md , Rahman Md. Habibur
Published: December 2021

Objective: Induction of colorectal cancer in Wister rats using titanium dioxide and dimethylhydrazine and treatment using the physical conjugate of 5-Fluorouracil and Curcumin, with a synergistic approach.Methods: Compatibility studies are evaluated by using FT-IR,Vero cell lines, and HCT-116 cell lines are used for evaluating the synergistic approach. This followed by induction using titanium dioxide and dimethylhydrazine in Wister rats and treatment using 5-Fluorouracil and Curcumin with pectin coating. Result: The samples were found to be compatible. The synergistic effect was obtained at 1:1, 1:2, 1:4, and 2:1 ratio, where 1:4 ratio shows a CI50 value of 0.896, selected further for the animal studies when studied in HCT 116 cell lines and found to be safe with Vero cell lines. Colorectal cancer was shown to be induced within 70 days of administration of titanium dioxide and dimethylhydrazine.1:4 ratio of 5-Fluorouracil and Curcumin (50:200) shows effective for the treatment of colorectal cancer within 28 days, proven using histopathology report, bodyweight analysis, and hematological reports.Conclusion: 5-Fluorouracil and curcumin (1:4) ratio works with a synergistic approach and was proven effective for the treatment of colorectal cancer induced bythe titanium dioxide and dimethylhydrazine.
Cost-effectiveness of a Transdiagnostic Psychotherapy Program for Youth With Common Mental Health Problems
Authors: Wolf Rasmus Trap , Jeppesen Pia , Pedersen Mette Maria Agner , Puggaard Louise Berg , Thastum Mikael , Bilenberg Niels , Thomsen Per Hove , Silverman Wendy K. , Plessen Kerstin Jessica , Neumer Simon-Peter , Correll Christoph U. , Pagsberg Anne Katrine , Gyrd-Hansen Dorte
Published: December 2021

Objectives: Our objective was to evaluate the cost-effectiveness of the transdiagnostic psychotherapy program Mind My Mind (MMM) for youth with common mental health problems using a cost-utility analysis (CUA) framework and data from a randomized controlled trial. Furthermore, we analyzed the impact of choice of informant with respect to both quality-of-life reporting and preference weights on the Incremental Cost Effectiveness Ratio (ICER). Methods: A total of 396 school-aged youth took part in the 6-month trial. CUAs were carried out for the trial-period and for four one-year extrapolation scenarios. Costs were based on a combination of budget and self-reported costs. Youths and parents were asked to report on the youth’s quality-of-life three times during the trial using the Child Health Utility 9D (CHU9D). Parental-reported CHU9D was used in the base case together with preference weights of a youth population. Analyses using self-reported CHU9D and preference weights of an adult population were also carried out. Results: The analysis of the trial period resulted in an ICER of €170,465. The analyses of the one-year scenarios resulted in ICERs between €23,653 and €50,480. The ICER increased by 24% and 71% compared to the base case when using self-reported CHU9D and adult preference weights, respectively. Conclusion: The MMM intervention has the potential to be cost-effective, but the ICER is dependent on the duration of the treatment effects. Results varied significantly with the choice of respondent and the choice of preference weights indicating that both factors should be considered when assessing CUA involving youth.
Tropical volcanism enhanced the East Asian summer monsoon during the last millennium
Authors: Liu Fei , Gao Chaochao , Chai Jing , Robock Alan , Wang Bin , Li Jinbao , Zhang Xu , Huang Gang , Dong Wenjie
Published: December 2021

Extreme East Asian summer monsoon (EASM) rainfall frequently induces floods that pose threats to millions of people across East Asia. The intensified EASM rainfall has been generally attributed to internal modes of climate variability, while external volcanic forcing has been suggested to suppress the EASM. In contrast to the hydrological weakening theory of volcanic eruptions, we present convergent empirical and modeling evidence for significant intensification of EASM rainfall in response to strong tropical volcanic eruptions. Our paleoclimate proxy analyses show a significantly increased EASM in the first summer after large tropical eruptions from 1470 AD to the present. The multi-proxy ensemble mean demonstrates that the occurrence of an El Niño in the first boreal winter after a volcanic eruption is necessary for the enhanced EASM. The results from the last-millennium climate model simulations show that a volcano-induced El Niño and the associated warm pool air-sea interaction intensify EASM precipitation, overwhelming volcanic-induced moisture deficiency. This work offers a new perspective on the intertwined relationship between external forcing and internal variability in the complex climate system and potential flood disasters resulting from tropical volcanic eruption.
Adaptive Sliding Mode Disturbance Observer Based Composite Trajectory Tracking Control for Robot Manipulator With Prescribed Performance
Authors: Shi Danni , Zhang Jinhui , Sun Zhongqi , Xia Yuanqing
Published: December 2021

In this paper, the problem of the composite trajectory tracking control for robot manipulator with lumped uncertainties including unmodeled dynamics and external disturbances is investigated. To achieve the active disturbance rejection, the adaptive sliding mode disturbance observer is proposed to estimate the unknown lumped uncertainties in the absence of the prior upper bound information on the lumped uncertainties. Then, by combining the non-singular terminal sliding mode control and prescribed performance control approaches, the composite trajectory tracking controller is designed, and not only the finite-time convergence of the trajectory tracking errors, but also the prescribed performances are guaranteed. Finally, by applying the proposed control scheme to a two-DOF manipulator system, the effectiveness and advantages are verified by numerical simulations.
Fluorescence blinking in MoS2 atomic layers by single photon energy transfer
Authors: He Mai , Ge Cuihuan , Braun Kai , Huang Lanyu , Yang Xin , Zhao Hepeng , Meixner Alfred , Wang Xiao , Pan Anlian
Published: December 2021

The quantum optical phenomena, such as single photon emission, in two-dimensional (2D) transition metal dichalcogenides (TMDCs) have triggered extensive researches on 2D material-based quantum optics and devices. By far, most reported quantum optical emissions in TMDCs are based on atomic defects in the material or the local confinement of excitons by introducing local stain or potential. In contrast, energy transfer between two materials could also manipulate the photon emission behaviors in materials, even at the single photon level. Along with the single-photon emission nature of zero-dimensional (0D) quantum dots (QDs) at room temperature, constructing a 0D-2D hybrid heterostructure may provide an effective way to regulate the quantum states related optical emissions of TMDCs. Here, we report on fluorescence blinking, a quantum phenomenon, from MoS2 atomic layers in QD/ MoS2 heterostructure at room temperature. We demonstrate the single-photon nature of the QDs in heterostructures by second-order photon correlation measurements. Based on the transient PL spectroscopy and PL time trajectories, we attribute the fluorescence blinking behavior in MoS2 to the single photon energy transfer from QD to MoS2. Our work opens the possibility to achieve correlated quantum emitters in TMDCs at room temperature by controlling the energy transfer between QD and TMDCs.
How Many Sexual Partners Are Too Many for Elderly Men From Rural China Who Visit Female Sex Workers Becoming HIV-Positive?
Authors: Yang Yi , Fan ShuangFeng , Liang Shu , Liu Yang , Li Yuan , Xi Jing , Yuan Dan , Xiao Jie
Published: December 2021

Objectives. To make clear how many sexual partners (SPs) are too many for elderly (≥50 years old) men becoming HIV-positive from rural China.Methods. We conducted a case-control study: 99 newly HIV (+) vs. 88 HIV (-) elderly men with similar age who visited female sex workers (FSW). Receiver-operating characteristics (ROC) curves and backward binary logistic regression was applied. Results. Cases had more SPs (315.66±401.33) than controls(14.63±25.63)in their lifetime, mainly commercial SPs(313.98±401.38 vs.12.81±25.85), similarly in the last three years. AUCs for HIV infection at number of accumulated SPs and of commercial SPs were 0.89 and 0.90, and correspondingly 0.79 and 0.81 in the last three years. Cut-off values were identified as 51.5, 52.5, 5.5 and 4.5 based on Youden’s indexes (0.715, 0.705, 0.612 and 0.601). Risky factors for HIV infection among elderly men were having 52-2002 SPs in their lifetime (AOR (95%CI): 56.33(11.36-279.25)), having 5-289 commercial SPs in the last three years (11.55(2.78-47.94)). Conclusions. ≥52 SPs in their lifetime and ≥5 FSW in the last three years are too many for elderly men from rural China becoming HIV-positive.
Emergence of Amoxicillin Resistance and Identification of Novel Mutations of the pbp1A Gene in Helicobacter pylori in Vietnam
Authors: Tran Trung Thien , Nguyen Anh Tuan , Quach Duc Trong , Pham Dao Thi-Hong , Cao Nga Minh , Nguyen Uyen Thi-Hong , Dang An Nguyen-Thanh , Tran Minh Anh , Quach Loc Huu , Tran Khiem Thien , Le Nhan Quang , Ung Viet Van , Vo Minh Ngoc-Quoc , Nguyen Danh Thanh , Kha Kha Dong , Tran Trung Le , Nguyen Vy Thuy
Published: December 2021

Background
Amoxicillin resistant Helicobacter pylori (H. pylori) strains seem to have increased over time in Vietnam. This threatens the effectiveness of H. pylori eradication therapies with this antibiotic. This study aimed to investigate the prevalence of primary resistance of H. pylori to amoxicillin and to assess its association with pbp1A point mutations in Vietnamese patients.
Materials and Methods
Naive patients who presented with dyspepsia undergoing upper gastrointestinal endoscopy were recruited. Rapid urease tests and PCR assays were used to diagnose H. pylori infection. Amoxicillin susceptibility was examined by E-tests. Molecular detection of the mutant pbp1A gene conferring amoxicillin resistance was carried out by real-time PCR followed by direct sequencing of the PCR products. Phylogenetic analyses were performed using the Tamura-Nei genetic distance model and the neighbour-joining tree building method.
Results
There were 308 patients (46.1% men and 53.9% women, p = 0.190) with H. pylori infection. The mean age of the patients was 40.5 ± 11.4 years, ranging from 18 to 74 years old. The E-test was used to determine the susceptibility to amoxicillin (minimum inhibitory concentration (MIC) ≤ 0.125 µg/ml) in 101 isolates, among which the rate of primarily resistant strains to amoxicillin was 25.7%. Then, 270 sequences of pbp1A gene fragments were analysed. There were 77 amino acid substitution positions investigated, spanning amino acids 310–596, with the proportion varying from 0.4–100%. Seven amino acid changes were significantly different between amoxicillin-sensitive (AmoxS) and amoxicillin-resistant (AmoxR) samples, including Phe366 to Leu (p < 0.001), Ser414 to Arg (p < 0.001), Glu/Asn464−465 (p = 0.009), Val469 to Met (p = 0.021), Phe473 to Val (p < 0.001), Asp479 to Glu (p = 0.044), and Ser/Ala/Gly595−596 (p = 0.001). Phylogenetic analyses suggested that other molecular mechanisms might contribute to amoxicillin resistance in H. pylori in addition to the alterations in PBP1A.
Conclusions
We reported the emergence of amoxicillin-resistant Helicobacter pylori strains in Vietnam and new mutations statistically associated with this antimicrobial resistance. Additional studies are necessary to identify the mechanisms contributing to this resistance in Vietnam.
Bilateral Retinal Vasculitis in Association with Systemic Sclerosis sine Scleroderma. A case report and brief review of the literature.
Authors: Fernandez Francisco Manuel Hermoso , Ortego-Centeno Norberto , Callejas-Rubio Jose Luis , García-Serrano Jose L.
Published: December 2021

Background: Systemic sclerosis sine scleroderma is a very rare subset characterized by the total or partial absence of cutaneous manifestations of systemic sclerosis with the occurrence of internal organ involvement and serologic abnormalities. The purpose of this article is to report a case showing a very rare association of bilateral retinal vasculitis (RV) and systemic sclerosis sine scleroderma (ssSSc). We show the description of a case report and revision of other medical histories, prospective and retrospective studies. Findings: A 40-year-old woman presented at our Hospital for blurry vision with her left eye (OS). Her best-corrected visual acuity was 20/20 in both eyes. Funduscopy examination showed bilateral occlusive vasculitis with proliferative retinopathy and vitreous hemorrhages. Retinography showed temporary sheathed and some occluded veins, surrounded by large number of retinal hemorrhages in both eyes. In fluorescein angiography were found areas of not perfused retina, also with telangiectasia and staining of retinal vessel’s walls. We found isolated microaneurysms in these ischemic areas. The ophthalmological treatment was confluent photocoagulation of the ischemic retina of both eyes, and vitrectomy of the right eye to treat his vitreous hemorrhage. The systemic treatment was corticosteroids and Adalimumab during two years; afterwards the stability was achieved. There was a lack of response to cyclosporine and azathioprine. The diagnosis comes years later after presenting: anticentromere antibodies, scleroderma pattern on capillaroscopy and esophageal manometry showing esophageal dysmotility with absent contractility.Conclusion: We report a rare association of RV and sclerosis sine scleroderma. RV can precede the development of ssSSc by several years.
Event-Free Survival after 68Ga-PSMA-11 PET/CT in recurrent Hormone-Sensitive Prostate Cancer (HSPC) patients eligible for Salvage Therapy.
Authors: Ceci Francesco , Rovera Guido , Iorio Giuseppe Carlo , Guarneri Alessia , Chiofalo Valeria , Passera Roberto , Oderda Marco , Dall’Armellina Sara , Liberini Virginia , Grimaldi Serena , Bellò Marilena , Gontero Paolo , Ricardi Umberto , Deandreis Désirée
Published: December 2021

Background/AimProstate-Specific-Membrane-Antigen/Positron Emission Tomography (PSMA-PET) detects with high accuracy disease-recurrence, leading to changes in the management of biochemically-recurrent (BCR) prostate cancer (PCa). However, data regarding the oncological outcomes of patients who performed PSMA-PET are needed. The aim of this study was to evaluate the incidence of clinically-relevant events during follow-up in patients who performed PSMA-PET for BCR after radical treatment. Materials and Methodsthis analysis included consecutive, hormone-sensitive, hormone-free, recurrent PCa patients (HSPC) enrolled through a prospective study. All patients were eligible for salvage therapy, having at least 24 months of follow-up after PSMA-PET. The primary endpoint was the Event-Free Survival (EFS), defined as the time between the PSMA-PET and the date of event/last follow-up. The Kaplan-Meier method was used to estimate the EFS curves. EFS was also investigated by Cox proportional hazards regression. Events were defined as: death, radiological progression or PSA recurrence after therapy. ResultsOne-hundred and seventy-six (n=176) patients were analyzed (median PSA 0.62 [IQR:0.43–1.00] ng/mL; median follow-up of 35.4 [IQR:26.5-40.3] months). The EFS was 78.8% at one year, 65.2% (2-years), and 52.2% (3-years). Patients with clinically relevant events had a significantly higher median PSA (0.81 [IQR:0.53-1.28] vs 0.51 [IQR:0.36-0.80] ng/mL) and a lower PSAdt (5.4 [IQR:3.7-11.6] vs 12.7 [IQR:6.6-24.3] months) (p<0,001) compared to event-free patients. The Kaplan-Meier curves showed that PSA>0.5 ng/mL, PSAdt≤6 months and a positive PSMA-PET result were associated with a higher event rate (p<0.01). No significant differences of event rates were observed in patients who received changes in therapy management after PSMA-PET vs. patients who did not receive therapy changes. Finally, PSA> 0.5 ng/mL and PSAdt≤ 6months were statistically significant event-predictors in multi-variate model (p<0.001). ConclusionIn this cohort of HSPC patients prospectively enrolled, low PSA and long PSAdt were significant predictors of event. Furthermore, a lower incidence of events was observed also in patients having negative PSMA-PET, since longer EFS was significantly more probable in case of a negative scan.
Closed-loop Controller Based on Reference Signal Tracking for Absence Seizures
Authors: Zhang Hudong , Chen Yuting , Xie Yan , Chai Yuan
Published: December 2021

Deep brain stimulation (DBS) targeting thalamus reticular nucleus (TRN) brain regions has been proven to play an irreplaceable role in the treatment of absence seizures. Compared with open-loop DBS, closed-loop DBS has been recognized by researchers for its advantages of significantly inhibiting seizures and having fewer side effects. However, due to the complexity of the nervous system, the mechanism of DBS control epilepsy is still unclear, which hinders the study of closed-loop DBS. In our study, based on the biophysical model jointly constituted by cortical, thalamic, and basal ganglia, we selected the 2-4 Hz spike and wave discharges (SWDs) of the cortical region as a biomarker for response to absence epilepsy, and the mean firing rate (MFR) of substantia nigra pars reticulata (SNr) was used as a reference signal for modulation of closed-loop DBS. Moreover, to obtain the linear relationship between the stimulus and the response, we adopted an algorithm that combines controlled auto-regressive (CAR) and recursive least squares (RLS), and we built a proportional integral (PI) controller to make the DBS stimulus parameters self-update to control the seizures. The numerical simulation results show that the closed-loop DBS controllers based on frequency modulation and amplitude modulation respectively not only successfully track the firing rate (FR) of SNr, but also significantly destroy the SWDs of cerebral cortex and restore it to the other two normal discharge modes.
Continue Or Not To Continue? Attitudes Towards Deprescribing Among Community- Dwelling Older Adults In China
Authors: Tan Jie , Wang MinHong , Pei XiaoRui , Sun Quan , Lu ChongJun , Wang Ying , Zhang Li , Wu Chenkai
Published: December 2021

Background: Inappropriate prescribing of medications and polypharmacy among older adults are associated with a wide range of adverse outcomes. It is critical to understand the attitudes towards deprescribing—reducing the use of potentially inappropriate medications (PIMs)—among this vulnerable group. Such information is particularly lacking in low - and middle-income countries.Methods: The present study examined attitudes towards deprescribing and individual-based characteristics that might be associated with these attitudes among community-dwelling older adults in China. We conducted a cross-sectional study through in-person interviews using the Patients' Attitudes Towards Deprescribing (PATD) and the revised PATD (rPATD) (version for older adults) questionnaires in two communities through the community-based physical examination platform in China. Participants were 65 years and older and had at least one chronic disease and one regular prescription medication.Results: Of the 1,897 participants in this study, average age was 73.8 years (SD=6.2 years) and 1,023 (53.9%) were women. The majority had one chronic disease (n=1,364 [71.9%]) and took 1-2 medications (n=1,483 [78.2%]). A total of 947 (50.0%) older adults reported being willing to stop taking one or more of their medicines if their physician said it was possible, and 1,204 (63.5%) older adults wanted to stop a medicine been taking for a long time. We did not find Individual-level factors to be associated with attitudes towards deprescribing. Conclusions: The proportions of participants’ willingness to deprescribing were much lower than what prior investigations among western populations reported. It is important to identify the reasons for the low wiliness to deprescribe and develop a patient-centered and practical deprescribing guideline that is suitable for Chinese older adults.
Assessing Mechanical Catheter Dysfunction in Peritoneal Dialysis Patients: A Case Control, Proof-of-Concept Study
Authors: Flores Krystell Oviedo , Kaltenegger Lukas , Eibensteiner Fabian , Unterwurzacher Markus , Kratochwill Klaus , Aufricht Christoph , König Franz , Vychytil Andreas
Published: December 2021

New guidelines on evaluation of peritoneal membrane function recommend ruling out catheter dysfunction when evaluating patients with low ultrafiltration capacity. We introduce the use of a combination of parameters obtained from daily measurements of the cycler software for predicting catheter dysfunction in automated peritoneal dialysis patients. Out of 117 patients treated between 2015 and 2021, all patients with verified catheter dysfunction (n=14) were identified and compared to controls (n=19). We retrieved cycler data for seven days each and tested parameters predictive capability of catheter dysfunction. Total number of alarms/week >7 as single predictive parameter of catheter dislocation identified 85.7% (sensitivity) of patients with dislocated catheter and 31.6% (1-specificity) of control patients. A combination of parameters (number of alarms/week >7, drain time >22 min, ultrafiltration of last fill <150 mL) where at least two of three parameters appeared identified the same proportion of patients with catheter dislocation, but was more accurate in identifying controls (21% false positive). An easily applicable combination of daily cycler readout parameters, also available in remote monitoring platforms can be used as predictor of inadequate catheter function during routine follow-up with potential for earlier diagnosis of this frequent complication in the future.
Hierarchical stabilization of emulsions with multi-scale interconnected droplets and ultra-low nanoparticle loadings
Authors: Cao Changqian , Abdelphata Elsayed , Meimanova Aigerim , Wang Jian , Yu Jiacheng , Pilapil Brandy , Gong Peng , Zhao Jinlu , Zhang Yuyang , Fang Fengjiao , Kantzas Apostolos , Trifkovic Milana , Bryant Steven , Pan Yongxin
Published: December 2021

Pickering stabilization by colloidal particles is a common strategy to disperse droplets of one fluid into another fluid in food, cosmetics and chemical industries1-3. For over a century, this kind of stabilization has been governed by constant surface coverage concepts in which particles irreversibly attach to the fluid–fluid interface. The need to cover sufficient interfacial area to prevent coalescence typically results in large loadings of particles, uniform droplet size, creation of rigid interface and closed-cell structure with small total area4-7. Here we report a stabilization mechanism that yields hierarchically structured oil-in-brine emulsions with high interfacial area, deformability, connectivity and long-term stability at unprecedentedly low nanoparticle loadings. The hierarchy in structure is achieved via dynamic cation-particle-droplet interactions in cascaded emulsification, which consists of i) formation of submicron oil droplets (~250 nm) lightly covered by hydrophilic polymer-coated iron oxide nanoparticles and polyvalent metal ions; ii) spontaneous formation of small droplets of nonpolar oil (~1 μm) stabilized by the nanodroplets and cations and iii) attachment of nanodroplet/small droplet clusters to bridge large unarmoured oil droplets (5-50 μm) in macroemulsions. This new mode of stabilization enables much more efficient use of nanoparticles, stabilizing a given size macroemulsion droplet at an order of magnitude smaller particle loading. Moreover, particle loading decreases with the 5/3 power of droplet size, rather than the first power typical of Pickering emulsions. Finally, cations play a novel and essential role in this mechanism, which cannot be accommodated in the conventional Pickering model. Our approach provides a new pathway for templating materials with better control over the structure, and for exploiting applications that are currently inaccessible for Pickering and surfactant stabilized emulsions.
Open Chromatin Analysis in Trypanosoma Cruzi Life Forms Highlights Critical Differences in Genomic Compartments and Developmental Regulation at tDNA Loci
Authors: Lima Alex RJ , Poubel Saloe B , Rosón Juliana N , de Lima Loyze PO , Costa-Silva Hellida M , Silva Herbert GS , Gonçalves Camila S , AF Galante Pedro , Holetz Fabiola , Motta Maria Cristina MM , Silber Ariel M , Elias MCarolina , Cunha Julia PC
Published: December 2021

Background: Genomic organization and gene expression regulation in trypanosomes are remarkable because protein-coding genes are organized into codirectional gene clusters with unrelated functions. Moreover, there is no dedicated promoter for each gene, resulting in polycistronic gene transcription, with posttranscriptional control playing a major role. Nonetheless, these parasites harbor epigenetic modifications at critical regulatory genome features that dynamically change among parasite stages, which are not fully understood. Results: Here, we investigated the impact of chromatin changes in a scenario commanded by posttranscriptional control exploring the parasite Trypanosoma cruzi and its differentiation program using genome-wide approaches supported by transmission electron microscopy. The integration of FAIRE and MNase-seq data, two complementary epigenomic approaches, enabled us to identify differences in T. cruzi genome compartments, putative transcriptional start regions and virulence factors. In addition, we also detected developmental chromatin regulation at tRNA loci (tDNA), which seems to be linked to the translation regulatory mechanism required for parasite differentiation. Strikingly, a positive correlation was observed between active chromatin and steady-state transcription levels. Conclusion: Taken together, our results indicate that chromatin changes reflect the unusual gene expression regulation of trypanosomes and the differences among parasite developmental stages, even in the context of a lack of canonical transcriptional control of protein-coding genes.
Carbon Composites From Iron-chelating Pyridine Nitrogen-rich Coordinated Nanosheets for Oxygen Reduction
Authors: Zhang Bing , Guo Hele , Zhang Longsheng , Zhang Xu , Zhang Chao , Liu Tianxi
Published: December 2021

The exploration of a noble-metal-free and nitrogen-doped carbon (M-N/C) composite electrocatalyst for the oxygen reduction reaction (ORR) remains a great challenge. The activities of the M-N/C composite electrocatalysts are mainly affected by the metal active sites, pyridinic nitrogen, and graphitic nitrogen. In the present work, the iron-coordinated self-assembly is proposed for the preparation of iron-chelating pyridine nitrogen-rich coordinated nanosheet (IPNCN) composites as an electrocatalyst. Due to the highly conjugated structure of the IPNCN precursor, the pyridine nitrogen elements at both ends of the tetrapyrido [3,2-a:2',3'-c:3'',2''-h:2''',3'''-j] phenazine (TP) provide the multiple ligands, and the coordination interactions between the irons and the pyridine nitrogen further improve the thermodynamic stability, where the metal active sites and nitrogen elements are uniformly distributed in the whole structure. The resultant IPNCN composites exhibit excellent ORR performance with an onset potential of 0.93 V and a half potential of 0.84 V. Furthermore, the IPNCN composite electrocatalysts show the higher methanol resistance and electrochemical durability than the commercial Pt/C catalysts. It could be convinced that the as-designed IPNCN composite catalysts would be a promising alternative to the noble metal Pt-based catalysts in the practical applications.
Inequalities In Caries Among Pre-School Italian Children With Different Background
Authors: Campus Guglielmo , Cocco Fabio , Strohmenger Laura , Wolf Thomas Gerhard , Balian Araxi , Arghittu Antonella , Cagetti Maria Grazia
Published: December 2021

Background: The study was aimed to describe caries prevalence and severity and health inequalities among Italian preschool children with European and non-European background and to explore the potential presence of a social gradient. Methods: The ICDAS (International Caries Detection and Assessment System) was recorded at school on 6,825 children (52.76% females). Caries frequency and severity was expressed as a proportion, recording the most severe ICDAS score observed. Socioeconomic status (SES) and behavioral habits of children/parents/caregivers were estimated by mean a standardized self-submitted questionnaire filled-in by parents. The Slope Index of Inequality (SII) based on regression of the mid-point value of caries experiences score for each SES group was calculated and a social gradient was generated as the weighted sum of the worst circumstances deriving from social explanatory variables. Children were stratified into four social gradient levels based on the number of worst options. Multivariate regression models (Zero-Inflated Negative Binomial logistic regression in children with European background and a logistic regression in children with non-European background) were used to elucidate the associations between all explanatory variables and health outcome (namely the caries prevalence). Mantel Haenszel trend of odds adjusted by immigrant background and area of living were calculated to study the existence, dimensions and direction of a social gradient in oral health. Results: Overall, 54.37% (95%CI 46.71–58.28%) of the children were caries-free; caries prevalence was statistically significant higher in children with non-European background compared to European children (72.59% vs 41.62% p<0.01). A statistically significant trend was observed for ICDAS 5/6 score and the worst social/behavioral level (Z=5.24, p<0.01). Conclusions: Data show how caries in preschool children is an unsolved public health problem especially in those with a non-European background. The proposed gradient was clearly able to identify children with the worst dental conditions.
Abnormal Methylation of SF-1 Gene Promoter Region in Endometrial Cancer and Its Mechanism
Authors: Huang Zhen , Jia Mingzhu , Jiang Peng , Deng Ying , Ding Shanshan , Lai Li , Hu Yicheng , Hu Zhuoying
Published: December 2021

We aim to investigate the methylation status, protein expression and clinical significance of the steroidogenic factor-1(SF-1) in endometrial carcinoma (EC), and explore the effect of abnormal methylation of SF-1 on the biological behaviour of EC. Bisulfite sequencing (BSP), western blotting (WB), and immunohistochemical were used to detect the methylation status and protein expression of SF-1 in EC tissues, paracancerous tissues and normal endometrial tissues. DNA methyltransferase inhibitor 5-Aza-CdR were used to treat HEC-1-A cell lines to demethylate SF-1. After treatment, WB and qPCR were used to detect the expression of SF-1 and its downstream target genes. Cell proliferation and apoptosis were detected by the EdU fluorescent labelling method and flow cytometry between the groups. Compared with paracancerous tissues and normal endometrial tissues, the expression of SF-1 protein in EC tissues was significantly increased (P﹤0.05). The percentage of methylated cytosine in the promoter region of the SF-1 gene in EC tissues (8.2%) was significantly lower than that in paracancerous tissues by 40.9% (P<0.05). Compared with the control group, after 5-Aza-CdR treatment, the methylation level of the SF-1 gene was significantly reduced (P﹤0.05), the expressions of SF-1 and its downstream target genes were significantly increased (P <0.05), the cell proliferation was enhanced and the cell apoptosis was significantly reduced (P <0.05). In conclusion, in EC, SF-1 gene was hypomethylated and the expression of SF-1 was increased, which promotes cell proliferation and inhibits cell apoptosis. SF-1 may become a new molecular target for early diagnosis and treatment in EC.
Hemicortical Resection and Biological Reconstruction using Allograft for Parosteal Osteosarcoma of the Distal Femur. A Case Series
Authors: Savvidou Olga D , Goumenos Stavros , Trikoupis Ioannis , Kaspiris Angelos , Melissaridou Dimitra , Gavriil Panagiotis , Georgoulis Jimmy , Papagelopoulos Panayiotis J
Published: December 2021

Background: Parosteal osteosarcoma (PAO), which is a surface osteosarcoma, can be treated with wide excision and endoprosthetic or allograft application. However, due to the low local recurrence and metastasis rate, when it appears in the posterior surface of the distal femur, can be managed with hemicortical wide resection and biological reconstruction with hemicortical allograft.The purpose of this study was to evaluate the oncological and functional outcomes of patients with parosteal osteosarcoma (PAO) of the posterior cortex of the distal femur who underwent biological reconstruction after hemicortical resection. Methods: Eleven patients who underwent wide tumor resection and defect reconstruction of the posterior surface of the distal femur using hemicortical allograft were studied retrospectively. Local recurrence, metastasis, complications and the functional outcome using the Musculoskeletal Tumor Society scoring system (MSTS Score) were evaluated.Results: The average postoperative follow-up period was 53.64 months (range, 30 to 84 months). At the latest follow up, all patients were free of the disease without appearing any metastases. A patient with local recurrence underwent revision surgery with fibula autograft reconstruction. The mean MSTS score was 93.45 ± 3.56. Conclusions: In patients with PAO of the posterior aspect of the distal femur the treatment of hemicortical resection and allograft reconstruction has satisfactory oncological and functional outcomes and low complication rates.
Staff-to-Residence Abuse in Nursing Homes: A Scoping Review
Authors: Hirt Julian , Adlbrecht Laura , Heinrich Steffen , Zeller Adelheid
Published: December 2021

Background: Elder abuse in long-term care is an important public health concern with social, health-related, and economic implications. Staff-to-resident abuse is of particular interest since institutions should protect residents’ rights and prevent harm. To provide an up-to date comprehensive overview of staff-to-resident abuse in nursing homes, we performed a scoping review considering types of abuse, their prevalence and associated factors, descriptions, experiences, and preventive interventions.Methods: We performed a scoping review following the framework provided by Arksey and O’Malley. We searched MEDLINE (via PubMed), CINAHL, PsycINFO via Ovid, and Cochrane Library. Additionally, we performed free web searching using Google Scholar and checked relevant reviews. Two reviewers independently selected studies. We narratively synthesised the results.Results: Out of 3876 references retrieved by our search, we included 46 studies in 47 reports. The prevalence rates of abuse varied widely, ranging from 0 to 93% depending on the type of abuse. Associated factors of abuse at the staff, resident, and nursing home level were evaluated inconsistently. Abuse was perceived ambiguous: even though it was considered unacceptable, it was underreported. We found only four studies addressing preventive interventions. Of these, four made recommendations for intervention development. Only one study with an experimental design examined a multi-component intervention including education and mutual support.Conclusions: The review yielded heterogenous evidence not allowing a concrete conclusion on prevalence and associated factors. However, the results show the significance of the problem and indicate that there are associate factors of abuse that can be influenced by appropriate interventions. These are amongst other staff education, organisational culture, and conditions. Further research should investigate the composition and content of preventive interventions and their potential to reduce abusive behaviours.
Correlation Analysis Between Uric Acid and Metabolic Syndrome in the Elderly Population
Authors: Nie Guqiao , Wan Jing Jing , Jiang Lei , Hou Shu Kai , Peng Wen
Published: December 2021

Background：The prevalence of metabolic syndrome in the elderly is gradually increasing，which accounts for the largest burden of non-communicable diseases worldwide and has direct effects on health. Research on the relationship between uric acid and metabolic syndrome in the elderly is relatively lacking. The purpose of this study is to explore the diagnostic value of uric acid levels for metabolic syndrome, compared to other components of metabolic syndrome.Materials and methods：We collected the physical examination data of 1,267 elderly people in the community in Wuhan, and used SPSS IBM 22.0 for data analysis. Perform correlation analysis, logistic regression analysis and draw ROC curve. Results：The prevalence of hyperuricemia was 28.1%, and metabolic syndrome was 18.6%; the uric acid level of the non-metabolic syndrome group was lower than that of the metabolic syndrome group (337.31 vs 381.91 µmol/ L; P<0.05); Pearson analysis revealed uric acid levels are correlated with blood pressure, BMI, triglyceride, high-density lipoprotein cholesterol. Logistic regression analysis results suggest that uric acid is a risk factor for metabolic syndrome. Metabolic syndrome components TG and HDL levels are also related to uric acid levels. The result is described as OR value and 95% CI (OR 1.003 [1.001, 1.005]). By drawing the ROC curve, we found that the area under the curve for uric acid to diagnose metabolic syndrome is 0.64 (sensitivity: 79.3%, specificity: 45.1%), which is similar to other components of metabolic syndrome. Conclusion：We confirmed the correlation between uric acid levels and metabolic syndrome in the elderly Chinese population.
Assessment of Compliance to Animal Source Foods Quality and Safety Standards in Uganda. A Case of Kampala and Mbarara Districts
Authors: Kungu Joseph M , Ejobi Francis , Atuheire Collins , Baluka Sylivia , Kiganira Dan Brian , Namyalo Edity , Meeme Rehema , Okuyo Bosco A
Published: December 2021

Animal source foods (ASFs) can be sources of illness when poorly handled both at the farms and during processing. Efforts have been undertaken by government to promote good food standards, quality and safety but have not paid off due to limited holistic involvement of all ASFs value chain actors like the farmers, transporters, traders, and the consumers. An assessment was conducted in Kampala and Mbarara districts to determine the level of compliance to existing food control standards.The findings are to help inform policies to adapt, promote and implement standards and quality of ASF products free or with minimal contamination, services to promote local industries and protect consumers as well as facilitate access to international markets. This assessment was carried out in Kampala and Mbarara district with major objective of mapping various institutions involved in designing and implementing food control standards with the core mandate lying with Uganda National Bureau of Standards and assessing of compliance to food control standards along the ASFs value chain.The studies were conducted in Kampala, Uganda’s capital and Mbarara, the second biggest city in the country. These districts constitute the major market hub of agricultural products due to their high consumer population. The ASFs value chain assessments were conducted through workshops using focus group discussions with stakeholders in the meat, milk, poultry and fish value chains.A number of organisations along the food chain were involved in designing and implementing of food safety standards and regulations, as well as regulatory norms for setting and controlling of quality standards for animal source foods in Uganda. These included; farmers, transporters, processors, academia, researchers, trade organisations, government institutions, private organisations, international bodies and consumers’ organisations.Majority of the outlet operators had both operating certificates and health certificates, however the remaining proportion that was noncompliant is still significant considering that they still distribute ASFs products. The study also observed that most of the measures required to ensure safety of ASFs are not followed along the food chain such as; poor transportation of animals and their products and use of antibiotics in animal feeds. It was also observed that product quality and cost of the product greatly contribute to the consumers’ demand and confidence for a particular animal source product.
Multi-timescale control of Southern Ocean diapycnal mixing over Atlantic tracer budgets
Authors: Ellison Elizabeth , Mashayekh Ali , Cimolo Laura
Published: December 2021

Oceanic cross-density (diapycnal) mixing helps sustain the ocean den- sity stratification and its Meridional Overturning Circulation (MOC) and is key to global tracer distributions. The Southern Ocean (SO) is a key region where different overturning cells connect, allowing nutri- ent and carbon rich Indian and Pacific deep waters, and oxygen rich Atlantic deep waters to resurface. The SO is also rife with localized intense diapycnal mixing due to breaking of internal waves induced by the interaction of energetic eddies and currents with rough topogra- phy. SO diapycnal mixing is believed to be of secondary importance for the MOC. Here we show that changes to SO mixing can cause sig- nificant alterations to Atlantic biogeochemical tracer distributions over short and long timescales in an idealized model of the MOC. While such alterations are dominated by the direct impact of changes in diapycnal mixing on tracer fluxes on annual to decadal timescales, on centennial timescales they are dominated by the mixing-induced variations in the advective transport of the tracers by the Atlantic MOC. This work sug- gests that an accurate representation of spatio-temporally variable local and non-local mixing processes in the SO is essential for climate mod- els’ ability to i) simulate the biogeochemical cycles and air sea carbon fluxes on decadal timescales, ii) represent the indirect impact of mixing- induced changes to MOC on biogeochemical cycles on longer timescales.
Meta-analysis of genetic association studies on gestational diabetes mellitus
Authors: BHUSHAN Ravi , Upadhyay Sonal , AWASTHI Shally , Panday Monika
Published: December 2021

Background

Several molecular epidemiological studies have analyzed the associations between genetic variants and the risk of gestational diabetes mellitus (GDM). However, all these studies suffer from inconsistent and conflicting results owing to relatively smaller sample sizes, fewer genetic variants included in the research, and limited statistical power. Hence, a coherent review and meta-analysis were carried out to provide a quantitative summary related to the associations of commonly studied SNPs with GDM risk.
Methods

Eligible studies were retrieved from PubMed,updated on Dec. 2019. Based on several inclusion and exclusion criteria, 71 articles with 42928 GDM patients and 77793 controls were finally considered for meta-analysis. The genotype data from 23 variants of sixteen genes were statistically analyzed using RevMan v 5.2 software. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the research article. Heterogeneity among studies was tested by I2 and odds ratio with 95% confidence interval (CI) was carried out for all five genetic models.
Results

The overall combined odds ratio reveals that variants like MTNR1B (rs1083963, rs1387153), GCK (rs1799884), CANP10 (rs3792267), and GCKR (rs780094) are significantly associated with GDM in all genetic models while CANP10 (rs5030952), ADRB (rs4994) and FTO (rs8050136) are not significantly associated with GDM in any genetic models. Variants MTNR1B (rs1083963, rs1387153) and GCK (rs1799884) are associated with increased risk (OR>1, p<0.05) of GDM, and all these are related to insulin secretion. Other variants related to insulin secretion like TCF7L2 (rs7903146) and SLC30A8 (rs1326634) are also associated with increased risk (OR>1, p<0.05) of GDM. On the contrary, CANP10 (rs3792267) and GCKR (rs780094) are found associated with decreased risk (OR<1, p<0.05) of GDM. Other variants are significantly associated with the GDM in at least one or more genetic models.
Conclusion

Our study identified that most of the variants related to insulin secretions like MTNR1B (rs1083963), GCK (rs1799884), TCF7L2 (rs7903146), GCKR (rs780094), and SLC30A8 (rs1326634) are more strongly associated (p<0.005) with GDM as compared to the variants related to the insulin resistance like PPARG (rs1801282), IRS1 (rs1801278) and ADIPOQ (rs266729).