bluuebunny/crossref_metadata_2025 huggingface dataset:
Islet amyloid polypeptide cross-seeds tau and drives the neurofibrillary pathology in Alzheimer’s disease
Authors: Zhang Guoxin , Meng Lanxia , Wang Zhihao , Peng Qinyu , Chen Guiqin , Xiong Jing , Zhang Zhentao
Published: January 2022

Background

The pathologic accumulation and aggregation of tau is a hallmark of tauopathies including Alzheimer’s disease (AD). However, the molecular mechanisms mediating tau aggregation in AD remain elusive. The incidence of AD is increased in patients with type 2 diabetes (T2DM), which is characterized by the amyloid deposition of islet amyloid polypeptide (IAPP) in the pancreas. However, the molecular mechanisms bridging AD and T2DM remain unknown.

Methods

We first examined the presence of IAPP in the neurofibrillary tangles of AD patients. Then we tested the effect of IAPP on tau aggregation. The biochemical and biological characteristics of the IAPP-tau fibrils were tested in vitro. The seeding activity and neurotoxicity of the IAPP-tau fibrils were confirmed in cultured neurons. Lastly, the effect of IAPP on tau pathology and cognitive impairments was determined by injecting the IAPP-tau fibrils and IAPP fibrils into the hippocampus of tau P301S mice.

Results

We found that IAPP interacts with tau and accelerates the formation of a more toxic strain, which shows distinct morphology with enhanced seeding activity and neurotoxicity in vitro. Intrahippocampal injection of the IAPP-tau strain into the tau P301S transgenic mice substantially promoted the spreading of tau pathology and induced more severe synapse loss and cognitive deficits, when compared with tau fibrils. Furthermore, intracerebral injection of synthetic IAPP fibrils initiated tauopathy in the brain of tau P301S transgenic mice.

Conclusions

These observations indicate that IAPP acts as a crucial mediator of tau pathology in AD, and provide a mechanistic explanation for the higher risk of AD in individuals with T2DM.
Perceived helpfulness of service sectors used for mental and substance use disorders: Findings from the WHO World Mental Health Surveys
Authors: Harris Meredith G. , Kazdin Alan E. , Munthali Richard J. , Vigo Daniel V. , Hwang Irving , Sampson Nancy A. , Al-Hamzawi Ali , Alonso Jordi , Andrade Laura Helena , Borges Guilherme , Bunting Brendan , Florescu Silvia , Gureje Oye , Karam Elie G. , Lee Sing , Navarro-Mateu Fernando , Nishi Daisuke , Rapsey Charlene , Scott Kate M. , Stagnaro Juan Carlos , Viana Maria Carmen , Wojtyniak Bogdan , Xavier Miguel , Kessler Ronald C.
Published: January 2022

Background

Mental healthcare is delivered across service sectors that differ in level of specialization and intervention modalities typically offered. Little is known about the perceived helpfulness of the combinations of service sectors that patients use.

Methods

Respondents 18 + years with 12-month DSM-IV mental or substance use disorders who saw a provider for mental health problems in the year before interview were identified from WHO World Mental Health surveys in 17 countries. Based upon the types of providers seen, patients were grouped into nine mutually exclusive single-sector or multi-sector ‘treatment profiles’. Perceived helpfulness was defined as the patient’s maximum rating of being helped (‘a lot’, ‘some’, ‘a little’ or ‘not at all’) of any type of provider seen in the profile. Logistic regression analysis was used to examine the joint associations of sociodemographics, disorder types, and treatment profiles with being helped ‘a lot’.

Results

Across all surveys combined, 29.4% (S.E. 0.6) of respondents with a 12-month disorder saw a provider in the past year (N = 3221). Of these patients, 58.2% (S.E. 1.0) reported being helped ‘a lot’. Odds of being helped ‘a lot’ were significantly higher (odds ratios [ORs] = 1.50–1.89) among the 12.9% of patients who used specialized multi-sector profiles involving both psychiatrists and other mental health specialists, compared to other patients, despite their high comorbidities. Lower odds of being helped ‘a lot’ were found among patients who were seen only in the general medical, psychiatrist, or other mental health specialty sectors (ORs = 0.46–0.71). Female gender and older age were associated with increased odds of being helped ‘a lot’. In models stratified by country income group, having 3 or more disorders (high-income countries only) and state-funded health insurance (low/middle-income countries only) were associated with increased odds of being helped ‘a lot’.

Conclusions

Patients who received specialized, multi-sector care were more likely than other patients to report being helped ‘a lot’. This result is consistent with previous research suggesting that persistence in help-seeking is associated with receiving helpful treatment. Given the nonrandom sorting of patients by types of providers seen and persistence in help-seeking, we cannot discount that selection bias may play some role in this pattern.
Perspectives of community processes in establishing community-based mental health services in Hong Kong: a case study
Authors: Lee Vincent W. P. , Lai Daniel W. L. , Ou Xiaoting
Published: January 2022

Background

Integrated Community Centres for Mental Wellness (ICCMWs) provide district-based community support services for patients discharged from mental health facilities and other residents in Hong Kong. However, selecting locations for these community centres is challenging primarily because of community opposition, which has introduced barriers to responses to service users’ interests and the operations of individual centres. This study examines public preferences for conflict resolution options, evaluates the feasibility of different consultation approaches, identifies effective methods for reducing public opposition and recommends possible approaches to public consultation and location selection.

Methods

A total of 74 individual interviews were conducted with key informants, including government personnel, service operators, politicians, resident representatives, community activists and service users. These interviewees were asked about their knowledge, experiences and perspectives of centre location selection processes.

Results

Interviews revealed that neighbourhood consultations for establishing community centres for mental wellness are time-consuming and did not yield a consensus of support from residents. In some instances, the government may decide to delay or withdraw location selection plans because of strong public opposition mainly because of bias and misunderstanding towards service users. However, the role of local politicians in mediating neighbourhood opinions and the government’s determination in planning location selection are essential for successfully selecting ICCMW locations.

Conclusion

Government departments should develop stronger collaboration to study target neighbourhoods and lobby stakeholders at earlier stages. Such investigations should involve identifying key stakeholders, the political and social dynamics of controversies and community demographics. A protocol specifying a time frame should be implemented to facilitate smooth and effective public consultation and community mental health service location selection processes.
Brain-wide TVA compensation allows rabies virus to retrograde target cell-type-specific projection neurons
Authors: Han Zengpeng , Luo Nengsong , Kou Jiaxin , Li Lei , Xu Zihong , Wei Siyuan , Wu Yang , Wang Jie , Ye Chaohui , Lin Kunzhang , Xu Fuqiang
Published: January 2022

Retrograde tracers based on viral vectors are powerful tools for the imaging and manipulation of upstream neural networks projecting to a specific brain region, and they play important roles in structural and functional studies of neural circuits. However, currently reported retrograde viral tracers have many limitations, such as brain area selectivity or the inability to retrograde label genetically defined brain-wide projection neurons. To overcome these limitations, a new retrograde tracing method, AAV-PHP.eB assisted retrograde tracing systems (PARTS) based on rabies virus, was established through brain-wide TVA-dependent targeting using an AAV-PHP.eB that efficiently crosses the blood–brain barrier in C57BL/6 J mice, and complementation of EnvA-pseudotyped defective rabies virus that specifically recognizes the TVA receptor. Furthermore, combined with Cre transgenic mice, cell-type-specific PARTS (cPARTS) was developed, which can retrograde label genetically defined brain-wide projection neurons. Our research provides new tools and technical support for the analysis of neural circuits.
ATAD3A mediates activation of RAS-independent mitochondrial ERK1/2 signaling, favoring head and neck cancer development
Authors: Lang Liwei , Loveless Reid , Dou Juan , Lam Tiffany , Chen Alex , Wang Fang , Sun Li , Juarez Jakeline , Qin Zhaohui Steve , Saba Nabil F. , Shay Chloe , Teng Yong
Published: January 2022

Background

Targeting mitochondrial oncoproteins presents a new concept in the development of effective cancer therapeutics. ATAD3A is a nuclear-encoded mitochondrial enzyme contributing to mitochondrial dynamics, cholesterol metabolism, and signal transduction. However, its impact and underlying regulatory mechanisms in cancers remain ill-defined.

Methods

We used head and neck squamous cell carcinoma (HNSCC) as a research platform and achieved gene depletion by lentiviral shRNA and CRISPR/Cas9. Molecular alterations were examined by RNA-sequencing, phospho-kinase profiling, Western blotting, RT-qPCR, immunohistochemistry, and immunoprecipitation. Cancer cell growth was assessed by MTT, colony formation, soft agar, and 3D cultures. The therapeutic efficacy in tumor development was evaluated in orthotopic tongue tumor NSG mice.

Results

ATAD3A is highly expressed in HNSCC tissues and cell lines. Loss of ATAD3A expression suppresses HNSCC cell growth and elicits tumor regression in orthotopic tumor-bearing mice, whereas gain of ATAD3A expression produces the opposite effects. From a mechanistic perspective, the tumor suppression induced by the overexpression of the Walker A dead mutant of ATAD3A (K358) produces a potent dominant-negative effect due to defective ATP-binding. Moreover, ATAD3A binds to ERK1/2 in the mitochondria of HNSCC cells in the presence of VDAC1, and this interaction is essential for the activation of mitochondrial ERK1/2 signaling. Most importantly, the ATAD3A-ERK1/2 signaling axis drives HNSCC development in a RAS-independent fashion and, thus, tumor suppression is more effectively achieved when ATAD3A knockout is combined with RAS inhibitor treatment.

Conclusions

These findings highlight the novel function of ATAD3A in regulating mitochondrial ERK1/2 activation that favors HNSCC development. Combined targeting of ATAD3A and RAS signaling may potentiate anticancer activity for HNSCC therapeutics.
Experiences of foot and ankle mobilisations combined with home stretches in people with diabetes: a qualitative study embedded in a proof‐of‐concept randomised controlled trial
Authors: Lepesis Vasileios , Marsden Jonathan , Paton Joanne , Rickard Alec , Latour Jos M.
Published: January 2022

Background

The benefits of exercise and staying active are widely reported in the literature, however adherence and engagement with exercise amongst people with long‐term illness and diabetes is poor. Physiotherapy aims to promote independence and physical activity using a range of strategies, including manual therapy and education/advice on exercises. However, low adherence impacts negatively on treatment outcomes. In this study, the practicality of physiotherapy interventions in patients who participate in a proof‐of‐concept (PoC) randomised controlled trial (RCT) will be considered.

Aim

To explore the experiences of people with diabetes who received an intervention package of foot and ankle mobilisations combined with home stretches for a 6‐week period.

Design

An embedded qualitative study in a proof‐of‐concept RCT using semi‐structured interviews and thematic analysis.

Participants

Purposive sample of 16 participants (mean age 73 years) with a diagnosis of diabetes (mean duration 13.4 years) were recruited.

Results

Analysis revealed seven themes informing the adherence and non‐adherence to the exercise intervention. Themes describing the positive experiences were: 1) support from others to do the exercises; 2) psychological factors to motivate exercise adherence; 2) physical factors contributing to exercise adherence; 4) acceptability of home exercises during and beyond the study. Other themes described barriers: 5) social factors that contributed to exercise disengagement; 6) emotional limitations that influence exercise avoidance; 7) physical circumstances that made exercise participation burdensome. Themes highlighted positive influences by physiotherapists, the motivation of doing exercises while participating in a study, improving the perceived range of motion in their foot and ankle and reducing discomfort in these joints whilst being more active with daily activities.

Conclusion

Our findings highlighted that the intervention of foot and ankle mobilisations combined with home stretches is feasible for study participants. Psycho‐social support, self‐efficacy, and physiotherapy support are motivational to adhere to the study intervention and might contribute to the success of a full‐scale RCT.
Prevalence of oral mucosal lesions in children in Xiangyun of Yunnan, China: a cross-sectional study
Authors: Yao Hui , Song Qianqian , Zhang Qiongyue , Tang Guoyao , Liu Mingshan
Published: January 2022

Background

This population-based cross-sectional study aimed to evaluate the prevalence of oral mucosal lesions (OMLs) in children in a rural area in China as epidemiological data on these conditions from such areas are insufficient.

Methods

A total of 3145 children in Xiangyun of Yunnan were enrolled. A socio-economic questionnaire and a field survey of OMLs were administered. We gathered information on factors (sex, age, caregiver, parental education, and last-month household income) that might be associated with OMLs in these children.

Results

OMLs in children in Xiangyun of Yunnan had a prevalence of 1.8% (95% CI; 1.3–2.3%). The most prevalent OML was oral ulcer (n = 11; 18.3%), followed by linea alba (n = 10; 16.7%), whereas the least prevalent OMLs were frenal tag (n = 1; 1.7%) and herpes labialis (n = 1; 1.7%). On unadjusted or adjusted regression, school-aged children had about 50% lower risk of OMLs than preschoolers.

Conclusions

These findings indicate that the prevalence of OMLs in Xiangyun of Yunnan is lower than previously reported. Additionally, the age might be associated with the occurrence of OMLs in children in Xiangyun of Yunnan, China.
Intertruncal versus classical approach to the ultrasound-guided supraclavicular brachial plexus block for upper extremity surgery: study protocol for a randomized non-inferiority trial
Authors: Luo Quehua , Cai Yujing , Xie Hanbin , Sun Guoliang , Guan Jianqiang , Zhu Yi , Yao Weifeng , Shu Haihua
Published: January 2022

Background

Ultrasound-guided intertruncal approach (IA) to the supraclavicular block (SB) is recently proposed as a new approach for local anesthetic (LA) injection in terms of the classical approach (CA) at the level of the first rib. The CA-SB has been proven to result in satisfying sensorimotor block, but associate with a high risk of intraneural injection. The aim of this randomized non-inferiority study is to explore whether IA-SB can obtain similar block dynamics, as the CA-SB, but avoiding an intraneural injection during the whole nerve block procedure.

Methods

The total 122 patients undergoing elective upper extremity surgery will be randomly allocated to receive either an IA-SB or a CA-SB using a double-injection (DI) technique. In the IA-SB group, a portion of LA (15 mL) is injected accurately to the intertruncal plane between the middle and lower trunks under real-time ultrasound guidance; then, the remaining volume (10 mL) is carefully distributed to the other intertruncal plane between the upper and middle trunks. In the CA-SB group, the DI technique will be carried out as described in Tran’s study. The primary outcome is the percentage of patients with a complete sensory blockade at 20 min with a predefined non-inferiority margin of − 5%. The secondary outcomes include the sensory-motor blockade of all 4 terminal nerves, onset times of the individual nerves within 30 min, block-related variables, and adverse events.

Discussion

The results will provide sensory-motor blockade-related parameters and safety of the ultrasound-guided intertruncal approach to the supraclavicular block, thereby promoting clinical practice.

Trial registration

Chinese Clinical Trial Registry ChiCTR2000040199. Registered on 25 November 2020
Linking the evolution of development of stem vascular system in Nyctaginaceae and its correlation to habit and species diversification
Authors: Cunha Neto Israel L. , Pace Marcelo R. , Hernández-Gutiérrez Rebeca , Angyalossy Veronica
Published: January 2022

Background

Alternative patterns of secondary growth in stems of Nyctaginaceae is present in all growth habits of the family and have been known for a long time. However, the interpretation of types of cambial variants have been controversial, given that different authors have given them different developmental interpretations. The different growth habits coupled with an enormous stem anatomical diversity offers the unique opportunity to investigate the evolution of complex developments, to address how these anatomies shifted within habits, and how the acquisition of novel cambial variants and habit transitions impacted the diversification of the family.

Methods

We integrated developmental data with a phylogenetic framework to investigate the diversity and evolution of stem anatomy in Nyctaginaceae using phylogenetic comparative methods, reconstructing ancestral states, and examining whether anatomical shifts correspond to species diversification rate shifts in the family.

Results

Two types of cambial variants, interxylary phloem and successive cambia, were recorded in Nyctaginaceae, which result from four different ontogenies. These ontogenetic trajectories depart from two distinct primary vascular structures (regular or polycyclic eustele) yet, they contain shared developmental stages which generate stem morphologies with deconstructed boundaries of morphological categories (continuum morphology). Unlike our a priori hypotheses, interxylary phloem is reconstructed as the ancestral character for the family, with three ontogenies characterized as successive cambia evolving in few taxa. Cambial variants are not contingent on habits, and their transitions are independent from species diversification.

Conclusions

Our findings suggest that multiple developmental mechanisms, such as heterochrony and heterotopy, generate the transitions between interxylary phloem and successive cambia. Intermediate between these two extremes are present in Nyctaginaceae, suggesting a continuum morphology across the family as a generator of anatomical diversity.
MRI-based radiomics analysis improves preoperative diagnostic performance for the depth of stromal invasion in patients with early stage cervical cancer
Authors: Ren Jing , Li Yuan , Yang Jun-Jun , Zhao Jia , Xiang Yang , Xia Chen , Cao Ying , Chen Bo , Guan Hui , Qi Ya-Fei , Tang Wen , Chen Kuan , He Yong-Lan , Jin Zheng-Yu , Xue Hua-Dan
Published: January 2022

Background

The depth of cervical stromal invasion is one of the important prognostic factors affecting decision-making for early stage cervical cancer (CC). This study aimed to develop and validate a T2-weighted imaging (T2WI)-based radiomics model and explore independent risk factors (factors with statistical significance in both univariate and multivariate analyses) of middle or deep stromal invasion in early stage CC.

Methods

Between March 2017 and March 2021, a total of 234 International Federation of Gynecology and Obstetrics IB1-IIA1 CC patients were enrolled and randomly divided into a training cohort (n = 188) and a validation cohort (n = 46). The radiomics features of each patient were extracted from preoperative sagittal T2WI, and key features were selected. After independent risk factors were identified, a combined model and nomogram incorporating radiomics signature and independent risk factors were developed. Diagnostic accuracy of radiologists was also evaluated.

Results

The maximal tumor diameter (MTD) on magnetic resonance imaging was identified as an independent risk factor. In the validation cohort, the radiomics model, MTD, and combined model showed areas under the curve of 0.879, 0.844, and 0.886. The radiomics model and combined model showed the same sensitivity and specificity of 87.9% and 84.6%, which were better than radiologists (sensitivity, senior = 75.7%, junior = 63.6%; specificity, senior = 69.2%, junior = 53.8%) and MTD (sensitivity = 69.7%, specificity = 76.9%).

Conclusion

MRI-based radiomics analysis outperformed radiologists for the preoperative diagnosis of middle or deep stromal invasion in early stage CC, and the probability can be individually evaluated by a nomogram.
Noninvasive assessment of clinical and pathological characteristics of patients with IgA nephropathy by diffusion kurtosis imaging
Authors: Liang Ping , Li Shichao , Yuan Guanjie , He Kangwen , Li Anqin , Hu Daoyu , Li Zhen , Xu Chuou
Published: January 2022

Objectives

To explore the diagnostic performance of diffusion kurtosis imaging (DKI) in evaluating the clinical and pathological characteristics of patients with immunoglobulin A nephropathy (IgAN) compared with conventional DWI.

Materials and methods

A total of 28 IgAN patients and 14 healthy volunteers prospectively underwent MRI examinations including coronal T2WI, axial T1WI, T2WI, and DWI sequences from September 2020 to August 2021. We measured mean kurtosis (MK), mean diffusivity (MD), and apparent diffusion coefficient (ADC) by using MR Body Diffusion Toolbox v1.4.0 (Siemens Healthcare). Patients were divided into three groups according to their estimated glomerular filtration rate (eGFR) (Group1, healthy volunteers without kidney disease or other diseases that affect renal function; Group2, IgAN patients with eGFR > 60 mL/min/1.73 m2; Group3, IgAN patients with eGFR < 60 mL/min/1.73 m2). One-way analysis of variance, Pearson or Spearman correlation, and receiver operating characteristic curves were applied in our statistical analysis.

Results

MKCortex and ADCCortex showed significant differences between the Group1 and Group2. MKCortex, MDCortex, ADCCortex, MKMedulla, and ADCMedulla showed significant differences between Group2 and Group3. MKCortex had the highest correlation with CKD stages (r = 0.749, p < 0.001), and tubulointerstitial lesion score (r = 0.656, p < 0.001). MDCortex had the highest correlation with glomerular lesion score (r = − 0.475, p = 0.011). MKCortex had the highest AUC (AUC = 0.923) for differentiating Group1 from Group2, and MDCortex had the highest AUC (AUC = 0.924) for differentiating Group2 from Group3, followed by MKMedulla (AUC = 0.923).

Conclusions

DKI is a feasible and reliable technique that can assess the clinical and pathological characteristics of IgAN patients and can provide more valuable information than conventional DWI, especially MKCortex.
Phlebosclerotic colitis: an analysis of clinical and CT findings in 29 patients with long-term follow-up
Authors: Ko Sheung-Fat , Chen Hong-Hwa , Huang Chung-Cheng , Lin Li-Han , Ng Shu-Hang , Lee Yi-Wei
Published: January 2022

Background

Phlebosclerotic colitis (PC) is a rare form of nonthrombotic colonic ischemia. This retrospective study analyzed the clinical findings and temporal CT changes in 29 PC patients with long-term follow-up.

Methods

Twenty-nine patients with characteristic CT features of PC collected between 1997 and 2020 were stratified into the acute abdomen group (AA-group) (n = 10), chronic-progressive group (CP-group) (n = 14) and chronic-stable group (CS-group) (n = 5). Clinical and CT changes during follow-up, comorbidities and final outcomes were compared.

Results

The AA-group exhibited a significantly thicker colonic wall and more involved segments and pericolic inflammation than the CP-group and CS-group on initial CT (p =  < 0.001–0.031). Seven patients in the AA-group who underwent right hemicolectomy had no recurrence during follow-up (mean ± SD, 7.1 ± 3.3 years), and the remaining three patients with renal or hepatic comorbidities who underwent conservative treatment died within 14 days. The CP-group showed significantly higher frequencies of chronic renal failure, urinary tract malignancies and liver cirrhosis than the AA-group (p = 0.005–0.008). In addition, CT follow-up (7.9 ± 4.3 years) showed significant increases in mesenteric venous calcifications, colonic wall thickening and involved colonic segments (p = 0.001–0.008) but conservative treatments were effective. The CS-group remained unchanged for years (8.2 ± 3.9 years).

Conclusions

Early surgery offered excellent prognosis in PC-related acute abdomen denoted by marked right colonic wall thickening and pericolic inflammation on CT. Conservative treatments with a wait-and-watch strategy were appropriate for CP-PC and CS-PC, albeit CP-PC harbored significant increases in calcifications, colonic wall thickening and affected segments in long-term CT follow-up.
Dental-derived mesenchymal stem cell sheets: a prospective tissue engineering for regenerative medicine
Authors: Chen Yuanting , Huang Huacong , Li Gaoxing , Yu Jianyu , Fang Fuchun , Qiu Wei
Published: January 2022

Stem cells transplantation is the main method of tissue engineering regeneration treatment, the viability and therapeutic efficiency are limited. Scaffold materials also play an important role in tissue engineering, whereas there are still many limitations, such as rejection and toxic side effects caused by scaffold materials. Cell sheet engineering is a scaffold-free tissue technology, which avoids the side effects of traditional scaffolds and maximizes the function of stem cells. It is increasingly being used in the field of tissue regenerative medicine. Dental-derived mesenchymal stem cells (DMSCs) are multipotent cells that exist in various dental tissues and can be used in stem cell-based therapy, which is impactful in regenerative medicine. Emerging evidences show that cell sheets derived from DMSCs have better effects in the field of regenerative medicine applications. Extracellular matrix (ECM) is the main component of cell sheets, which is a dynamic repository of signalling biological molecules and has a variety of biological functions and may play an important role in the application of cell sheets. In this review, we summarized the application status, mechanisms that sheets and ECM may play and future prospect of DMSC sheets on regeneration medicine.
Matrix vesicles from dental follicle cells improve alveolar bone regeneration via activation of the PLC/PKC/MAPK pathway
Authors: Yi Genzheng , Zhang Siyuan , Ma Yue , Yang Xueting , Huo Fangjun , Chen Yan , Yang Bo , Tian Weidong
Published: January 2022

Background

The regeneration of bone loss that occurs after periodontal diseases is a significant challenge in clinical dentistry. Extracellular vesicles (EVs)-based cell-free regenerative therapies represent a promising alternative for traditional treatments. Developmental biology suggests matrix vesicles (MVs), a subtype of EVs, contain mineralizing-related biomolecules and play an important role in osteogenesis. Thus, we explore the therapeutic benefits and expect to find an optimized strategy for MV application.

Methods

Healthy human dental follicle cells (DFCs) were cultured with the osteogenic medium to generate MVs. Media MVs (MMVs) were isolated from culture supernatant, and collagenase-released MVs (CRMVs) were acquired from collagenase-digested cell suspension. We compared the biological features of the two MVs and investigated their induction of cell proliferation, migration, mineralization, and the modulation of osteogenic genes expression. Furthermore, we investigated the long-term regenerative capacity of MMVs and CRMVs in an alveolar bone defect rat model.

Results

We found that both DFC-derived MMVs and CRMVs effectively improved the proliferation, migration, and osteogenic differentiation of DFCs. Notably, CRMVs showed better bone regeneration capabilities. Compared to MMVs, CRMVs-induced DFCs exhibited increased synthesis of osteogenic marker proteins including ALP, OCN, OPN, and MMP-2. In the treatment of murine alveolar bone defects, CRMV-loaded collagen scaffold brought more significant therapeutic outcomes with less unhealing areas and more mature bone tissues in comparison with MMVs and acquired the effects resembling DFCs-based treatment. Furthermore, the western blotting results demonstrated the activation of the PLC/PKC/MAPK pathway in CRMVs-induced DFCs, while this cascade was inhibited by MMVs.

Conclusions

In summary, our findings revealed a novel cell-free regenerative therapy for repairing alveolar bone defects by specific MV subtypes and suggest that PLC/PKC/MAPK pathways contribute to MVs-mediated alveolar bone regeneration.
LINC01119 negatively regulates osteogenic differentiation of mesenchymal stem cells via the Wnt pathway by targeting FZD4
Authors: Gao Hongwei , Dong Hui , Zheng Jiachun , Jiang Xufeng , Gong Mingzhi , Hu Le , He Jinshan , Wang Yongxiang
Published: January 2022

Background

Mesenchymal stem cells (MSCs) can differentiate into diverse cell types under specific conditions. Dysfunction in the osteogenic differentiation of MSCs can result in bone metabolism-related diseases, including osteoporosis. Accumulating evidence has revealed that long non-coding RNA (lncRNAs) play critical regulatory roles during MSC differentiation.

Methods

In the present study, we identified an evolutionarily conserved lncRNA expressed during the osteogenic differentiation of MSCs, which we termed LINC01119. We first identified LINC01119 as a negative regulator of the osteogenic differentiation of MSCs.

Results

LINC01119 knockdown markedly induced calcium deposition in bone marrow MSCs and promoted the osteogenic differentiation of MSCs. More importantly, we demonstrated the underlying molecular basis through which LINC01119 regulates osteogenesis via the Wnt pathway by targeting FZD4. Furthermore, we observed that transcription factor EBF3 could directly bind the promoter site of LINC01119.

Conclusions

We first explored the molecular regulatory mechanism of LINC01119 during the osteogenic differentiation of MSCs and revealed that LINC01119 negatively regulates osteogenesis through the Wnt pathway by targeting FZD4.
Factors predisposing women and children to indoor air pollution in rural villages, Western Kenya
Authors: Dida Gabriel O. , Lutta Patrick O. , Abuom Paul O. , Mestrovic Tomislav , Anyona Douglas N.
Published: January 2022

Background

Indoor air pollution (IAP) remains a major global public health hazard more so in developing countries where use of fossil fuels is still very common. However, despite the popularity of kerosene and fuelwood as energy sources among many households in the Sub-Saharan Africa, little is known about their health effects and the predisposing factors particularly on those with direct exposure. This study sought to relate indoor air pollution exposure to self-reported prevalence of respiratory outcomes including (sputum production, congestion, breathing difficulties, eye problems, fatigue, and headaches and wheezing) among women and children of Trans Nzoia County, in the rural villages of western Kenya.

Methods

In this cross-sectional survey, simple random technique was used to select 251 households from 14 villages. Households were the sampling units, while the woman of the household with/or in custody of a child aged less than 5 years old were the unit of analysis. A total of 251 women with/or in custody of a child aged less than 5 years old took part in the study. A structured questionnaire was used to collect information on cause and effects of IAP among women and children. Data was analyzed descriptively and inferentially. We used Poisson generalized linear models with IAP symptoms and indoor cooking as dependent variables and household profiles and other socio-demographics as independent variables to identify the factors that affect health outcome.

Results

Mean age of respondents was 36.49 years, (95% CI [35.5, 37.5]). Most (64.5%) houses were semi-permanent, with 58.6% having an average kitchen size (5.6 m2). Wood and kerosene were the most preferred fuel types for cooking (96.8%) and lighting (97.4%), respectively. Smoke from the wood was identified as the dominant (96.8%) source of IAP. Most women (92.0%) and children (95.4%) had coughs of varying intensities during the year, while 31.5% of the women reported wheezing. About 98% of them experienced fatigued and headaches. Use of wood fuel was associated with increased coughing (p = 0.03), phlegm (p = 0.02), wheezing (p = 0.04), eye problems (p = 0.03) and headaches (p = 0.01) among women and children in the previous 24 h. Education level, ventilation, main fuel source used in 24 h, indoor cooking and house type were significantly associated with IAP health effects (p ≤ 0.05).

Conclusions

Supporting the impoverished households and increasing their level of awareness on health-effects of IAP occasioned by use of biomass fuel while cooking indoors may be the first step in implementing a programme aimed at reducing exposure among rural households in Trans Nzoia County, in rural parts of Western Kenya.
Faecal microbiota transplantation reduces amounts of antibiotic resistance genes in patients with multidrug-resistant organisms
Authors: Hyun JongHoon , Lee Sang Kil , Cheon Jae Hee , Yong Dong Eun , Koh Hong , Kang Yun Koo , Kim Moo Hyun , Sohn Yujin , Cho Yunsuk , Baek Yae Jee , Kim Jung Ho , Ahn Jin Young , Jeong Su Jin , Yeom Joon Sup , Choi Jun Yong
Published: January 2022

Background

Multidrug-resistant organisms (MDROs) such as vancomycin-resistant enterococci (VRE) and carbapenemase-producing Enterobacteriaceae (CPE) are associated with prolonged hospitalisation, increased medical costs, and severe infections. Faecal microbiota transplantation (FMT) has emerged as an important strategy for decolonisation. This study aimed to evaluate the genetic response of MDROs to FMT.

Methods

A single-centre prospective study was conducted on patients infected with VRE, CPE, or VRE/CPE who underwent FMT between May 2018 and April 2019. Genetic response was assessed as the change in the expression of the resistance genes VanA, blaKPC, blaNDM, and blaOXA on days 1, 7, 14, and 28 by real-time reverse-transcription polymerase chain reaction.

Results

Twenty-nine patients received FMT, of which 26 (59.3%) were infected with VRE, 5 (11.1%) with CPE, and 8 (29.6%) with VRE/CPE. The mean duration of MDRO carriage before FMT was 71 days. Seventeen patients (63.0%) used antibiotics within a week of FMT. In a culture-dependent method, the expression of VanA and overall genes significantly decreased (p = 0.011 and p = 0.003 respectively). In a culture-independent method, VanA, blaNDM, and overall gene expression significantly decreased over time after FMT (p = 0.047, p = 0.048, p = 0.002, respectively). Similar results were confirmed following comparison between each time point in both the culture-dependent and -independent methods. Regression analysis did not reveal important factors underlying the genetic response after FMT. No adverse events were observed.

Conclusion

FMT in patients infected with MDROs downregulates the expression of resistance genes, especially VanA, and facilitates MDRO decolonisation.
A framework for research into continental ancestry groups of the UK Biobank
Authors: Constantinescu Andrei-Emil , Mitchell Ruth E. , Zheng Jie , Bull Caroline J. , Timpson Nicholas J. , Amulic Borko , Vincent Emma E. , Hughes David A.
Published: January 2022

Background

The UK Biobank is a large prospective cohort, based in the UK, that has deep phenotypic and genomic data on roughly a half a million individuals. Included in this resource are data on approximately 78,000 individuals with “non-white British ancestry.” While most epidemiology studies have focused predominantly on populations of European ancestry, there is an opportunity to contribute to the study of health and disease for a broader segment of the population by making use of the UK Biobank’s “non-white British ancestry” samples. Here, we present an empirical description of the continental ancestry and population structure among the individuals in this UK Biobank subset.

Results

Reference populations from the 1000 Genomes Project for Africa, Europe, East Asia, and South Asia were used to estimate ancestry for each individual. Those with at least 80% ancestry in one of these four continental ancestry groups were taken forward (N = 62,484). Principal component and K-means clustering analyses were used to identify and characterize population structure within each ancestry group. Of the approximately 78,000 individuals in the UK Biobank that are of “non-white British” ancestry, 50,685, 6653, 2782, and 2364 individuals were associated to the European, African, South Asian, and East Asian continental ancestry groups, respectively. Each continental ancestry group exhibits prominent population structure that is consistent with self-reported country of birth data and geography.

Conclusions

Methods outlined here provide an avenue to leverage UK Biobank’s deeply phenotyped data allowing researchers to maximize its potential in the study of health and disease in individuals of non-white British ancestry.
Predicting temperature and precipitation during the flood season based on teleconnection
Authors: Jung Jaewon , Kim Hung Soo
Published: January 2022

In recent years, the damages resulting from abnormal hydrometeorological climate have substantially increased over the world due to the climate variability and change. Especially, the flood damage has been severely occurred during the flood season almost every year in Korea. For an example, we had the localized heavy rainfalls for 54 days in flood season of 2020 and had huge property damage and loss of life. Therefore, the study needs to be conducted to improve the predictive power of seasonal time-scale forecasts spanning one to several months for the damage reduction and prevention. In this regard, this study aims to provide a priori predictions (several months ahead) of the climate variable at target sites with a statistical method based on teleconnection with global climatic conditions. Herein, the paradigm of the temperature and precipitation prediction in the Geum river basin in Korea is presented. The purposes of the study are also (1) to analyse the characteristics of summer temperatures and precipitation according to the occurrence of El Niño/La Niña and (2) to suggest a seasonal prediction model that can consider the effects of the occurrence of El Niño and La Niña during the flood season. The model is constructed by classifying the data period into El Niño, La Niña, and neutral status. Then we have shown that the prediction model improves the predictive power for the predictions of climate variables such as temperature and precipitation at mid-latitude stations which Korea is located. Therefore, this study demonstrates the possibility of improving the predictive power for forecasting temperature and precipitation by the prediction model considering climate variability.
Evolution of the magma plumbing system of Miyakejima volcano with periodic recharge of basaltic magmas
Authors: Geshi Nobuo , Oikawa Teruki , Weller Derek J. , Conway Chris E.
Published: January 2022

Defining the variations in petrological characteristics of erupted magmas within a high-resolution chronostratigraphy provides a necessary framework for monitoring the long-term activity and eruption potential of an active volcano. Here, we investigate the evolution of the magmatic system of Miyakejima volcano, Japan, between the last two caldera-forming eruptions, at ~ 2.3 ka and AD 2000, based on new stratigraphic constraints, radiocarbon ages, and whole-rock geochemical data. The activity of Miyakejima during this interval can be divided into three magmatic periods based on cyclic whole-rock compositional trends. Period 1 spans the interval between ~ 2.3 ka and the 7th century, from the Hatchodaira eruption with caldera collapse to immediately before the Suoana–Kazahaya eruption. Period 2 spans the time period between the seventh century and the fourteenth century, from the Suoana–Kazahaya to the Sonei–bokujyo eruptions. Period 3 covers the period from the two major flank eruptions that occurred in the sixteenth century to the end of the twentieth century until the last caldera-collapse event in AD 2000. The eruption rate decreased from 0.5 km3 per 1000 years in Period 1 to ~ 0.2 km3 per 1000 years in Period 2 and 3. Recharge of primitive basaltic magmas into shallower crustal systems triggered extensive basaltic fissure eruptions at the beginning of each period. Progressively increasing whole-rock SiO2 contents of the hybrid magmas in subsequent eruptions indicates continuous fractional crystallization in small shallow magma chambers which formed at the start of each magmatic period. Intermittent injections of basaltic magma into shallow magma chambers induced magma mixing that caused eruption of hybrid basaltic andesite in each period. We suggest that some basaltic magmas formed isolated magma reservoirs at shallow depth, in which rapid fractionation was able to occur. Rupturing of these isolated magma storage regions filled with gas-rich evolved magma can lead to violent ejection of andesitic magmas, such as for the Suoana–Kazahaya eruption in the seventh century. Our results suggest two main scenarios of eruption for the basaltic magma system at Miyakejima and similar mafic volcanoes in the northern Izu–Bonin arc; (1) eruption of voluminous basaltic lavas after the recharge of primitive basaltic magmas into the shallow magmatic system, and (2) explosive fissure eruption by rupturing of isolated magma bodies filled with gas-rich evolved magmas.

Graphical Abstract
Unusual giant multilocular thymic cyst with mature teratoma including a carcinoid component in the mediastinum
Authors: Manabe Takehiko , Kajiyama Kenta , Iwanami Takashi , Hanagiri Takeshi , Sako Tatsuhiko
Published: January 2022

Background

Teratoma is the second most common mediastinal neoplasm, but malignant transformation in mature teratomas is uncommon, and cases of carcinoid tumor with teratoma are described in only a few studies. In addition, multilocular thymic cyst associated with mature mediastinal teratoma is also a rare entity. There have been no reports of case with the coexistence of these three pathological lesions.

Case presentation

The patient was a 24-year-old man who was referred to our hospital due to a 2-day history of left shoulder pain, a feeling of severe chest tightness and high fever. Pre-operative computed tomography (CT) showed a large, fluid-filled and well-demarcated multilocular cyst in the anterior to superior mediastinum measuring up to 12 cm in size. Contrast-enhanced CT also revealed that the tumor contained a solid component with slight contrast enhancement and spotty wall-thickening septation. Therefore, cystic thymoma, thymic cyst, cystic teratoma, or germ cell tumor with an inflammatory reaction were considered as differential diagnoses. The patient underwent tumor extirpation under median sternotomy. The pathological diagnosis was multilocular thymic cyst with mature teratoma including carcinoid tumor (Grade 2) in the mediastinum.

Conclusions

The relationship between thymic cyst, teratoma and carcinoid tumor is unclear at present; therefore, further research is needed to clarify the relationship between these entities. In this report, we present a case of multilocular thymic cyst with mature teratoma including a carcinoid component in the mediastinum that was detected by complete surgical resection.
The effect of initiation of urate-lowering treatment during a gout flare on the current episode: a meta-analysis of randomized controlled trials
Authors: Jia Ertao , Yao Xiaoling , Geng Hongling , Zhong Li , Xie Jingjing , Xiao Yuya , Jiang Yubao , Qiu Xia , Xiao Min , Zhang Yanying , Tang Dabin , Wei Jiaxin , Zhang Jianyong
Published: January 2022

Objective

The objective was to evaluate whether initiation of urate-lowering treatment (ULT) during an acute gout flare prolonged the current episode.

Methods

A comprehensive search of MEDLINE and Web of Science databases was conducted from their inception to 15 March 2021. Five randomized controlled trials (RCTs) with 381 patients met the inclusion criteria. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were used for estimating the clinical efficacy of ULT in acute gout.

Results

There was no statistical difference in days to resolution (intent-to-treat analysis) (SMD, 0.68; 95% CI − 0.42 to 1.78; I2, 49%; p = 0.22), the pain visual analogue score (VAS) by day 10 (SMD, − 0.07; 95% CI − 0.30 to 0.16; I2, 0%; p = 0.53), C-reactive protein (CRP) from day 7 to 10 (SMD, − 1.14; 95% CI − 5.63 to 3.36; I2, 55%; p = 0.62), erythrocyte sedimentation rate (ESR) from day 7 to 10 (SMD, − 2.51; 95% CI − 5.46 to 0.45; I2, 0%; p = 0.10) and the recurrence of gout flares within 28–30 days (OR 0.78; 95% CI 0.29 to 2.09; I2, 0%; p = 0.62).

Conclusion

Initiation of ULT during an acute gout flare did not prolong the duration of the flare. However, larger sample size studies are needed to confirm this finding.

Trial registration number PROSPERO (CRD42021234581).
The nanocomposites designs of phytomolecules from medicinal and aromatic plants: promising anticancer-antiviral applications
Authors: Kaplan Ayse
Published: January 2022

Background

Nowadays, researchers are moving toward a herbal approach to cancer treatment because of the harmful effects of synthetic anti-tumor drugs. The evaluation of active compounds with plant origin may help in the remedy of human illnesses in the future. These active compounds have direct or indirect curative efficacies on difficult to cure diseases such as cancer. Investigation of nanoforms of these active compounds is one of the curious topics of the scientific community.

Main body

Saffron and its components obtained fromCrocus sativa, essential oils obtained from lavender,Syzygium aromaticumcalled cloves andBeta vulgarisare known for their anticancer effects. Nano-drugs are designed to increase the anticancer activity of plant-derived drugs. Herbal extracts operate very great in the production of nanoparticles. The aim is to ensure that only the nano-drug is delivered to the tumor site. Furthermore, nanoparticles have hazardous effects when analyzed at elevated doses, but this issue can be doped together with plant extracts.

Short conclusions

The nanocomposites (graphene oxide, solid lipid nano and nanoemulsion) of phytomolecules obtained from saffron, clove, lavender and red beet may be effective in minimizing these toxic effects. In the near future, detecting the anticancer molecular mechanisms of these naturally derived compounds and nanocomposites could contribute to further cancer research. Apart from these, these compounds and its nanocomposites could have antiviral effects against today's threat covid-19 virus. Consequently, more promising anticancer and antiviral agents would be discovered.

Graphical abstract