bluuebunny/crossref_metadata_2025 huggingface dataset:
Disability support and reincarceration after a first adult prison custody episode for people with intellectual disability in New South Wales, Australia
Authors: Trofimovs Julian , Srasuebkul Preeyaporn , Trollor Julian N , Dowse Leanne
Published: March 2022

Prisoners with an intellectual disability (ID) are an over-represented group in custody, with studies indicating this group is more likely to reoffend and be reincarcerated than the general prison population. While prisoners with ID share many of the same risk factors for recidivism as the general prison population, the lack of adequate disability support has been argued to be an additional key driver of recidivism for this group. This study aims to investigate reincarceration and factors associated with reincarceration after a first adult custody episode, including the impact of provision of general and specialist disability supports. The study used linked disability support services and custody data to identify a cohort of 1,129 prisoners with ID who were released from a first adult custodial episode in New South Wales (NSW) between 2005 and 2015. Over the follow-up period, the linked custody data showed that 72% (813) of those identified with an ID and released from a first adult custodial episode returned to prison, of which 76% (617) received no post-release disability support. This study found that 27% (308) of the study cohort had received a disability support service post-release from adult custody. Receipt of disability support was associated with a lower risk of reincarceration, while younger age and shorter duration of the custodial episode were associated with higher risk of reincarceration. The potential for disability support to lower risk of reincarceration highlights the importance of funding programmes that connect prisoners with ID to appropriate post-release disability supports.
Analysis of tiles produced from a schist material and their ultraviolet, near-infrared, mid-infrared, longwave-infrared and far-infrared spectra
Authors: Mutlu Hulya Kuru , Mutlu Atakan
Published: March 2022

Clays are used in the general production of earthen tiles. In this study, the production and characterization of earthen tiles from schist, a clayey rock formed by metamorphism of mudstone or shale, was investigated. The impact of tiles on atmospheric temperature through their absorption of the visible, near-infrared and far-infrared wavelength regions is evaluated. In particular, the absorption of ultraviolet and infrared radiation by the tiles was evaluated, as this could have beneficial applications for human health and the environment. UV-A radiation (320–400 nm) is not absorbed by the atmosphere, but schist materials absorb UV-A, which can contribute to melanoma formation (i.e. cancer). Field-emission scanning electron microscopy, X-ray fluorescence spectrometry and X-ray diffraction were used for the analysis of the schist materials. The tile-production stages of schist materials (drying, firing, water absorption rate, etc.) were tested at Hatipoglu Gunes Tile and Brick Industry, Inc. (Turkey). The tiles fired at 950°C and 1000°C comply with the industry standard compressive strength values for fired tiles (when converted to industry production conditions) and were 156.15 and 123.20 kg cm–2, respectively.
Substitution of ‘small’ divalent cations (e.g. Mg) for Si and Al in the nepheline tetrahedral framework: 1. Calculation of atomic formulae and stoichiometry parameters
Authors: Henderson C. Michael B. , Oliveira Ítalo Lopes de
Published: March 2022

A recent review paper on nepheline solid solutions dealt mainly with sodic varieties from nepheline syenites and differentiated alkali basaltic sills. Excel spreadsheets were provided for recalculating cell formulae in terms of the stoichiometric parameters ΔAlcavity cation charge and ΔTframework charge and molecular percentages of the end-members Ne, Ks, Ca-nepheline and excess Si (Qxs). Small amounts of tetrahedral divalent species (usually <0.10 wt.% though with up to 0.33 wt.% MgO) were related to a stuffed-tridymite end-member of ideal formula K8Mg4Si12O32 (denoted KsT2+-nepheline), although the equations used to calculate these end-members only considered Si, Al and Fe3+ as tetrahedral framework species. Recently, K-rich nepheline and kalsilite which contain up 0.54 wt.% MgO have been found in some feldspar-free mafic potassic volcanic rocks from central Brazil. Equations have been developed to deal rigorously with the presence of significant amounts of Mg (and Mn) in recalculating nepheline solid-solution parameters. In two related communications reworked spreadsheets are provided with examples of their use. High quality microprobe analyses of nepheline and kalsilite from magmatic rocks must include analyses for Mg and Mn and, if possible, estimates of Fe2+ contents.
Peanut and cotton intercropping increases productivity and economic returns through regulating plant nutrient accumulation and soil microbial communities
Authors: Xie Wei , Zhang Kai , Wang Xiaoying , Zou Xiaoxia , Zhang Xiaojun , Yu Xiaona , Wang Yuefu , Si Tong
Published: March 2022

Background

Intercropping (IC) has been widely adopted by farmers for enhancing crop productivity and economic returns; however, the underpinning mechanisms from the perspective of below-ground interspecific interactions are only partly understood especially when intercropping practices under saline soil conditions. By using permeable (100 μm) and impermeable (solid) root barriers in a multi-site field experiment, we aimed to study the impact of root-root interactions on nutrient accumulation, soil microbial communities, crop yield, and economic returns in a peanut/cotton IC system under non-saline, secondary-saline, and coastal saline soil conditions of China.

Results

The results indicate that IC decreased the peanut pods yield by 14.00, 10.01, and 16.52% while increased the seed cotton yield by 61.99, 66.00, and 58.51%, respectively in three experimental positions, and consequently enhanced the economic returns by compared with monoculture of peanut (MP) and cotton (MC). The higher accumulations of nutrients such as nitrogen (N), phosphorus (P), and potassium (K) were also observed in IC not only in the soil but also in vegetative tissues and reproductive organs of peanut. Bacterial community structure analysis under normal growth conditions reveals that IC dramatically altered the soil bacterial abundance composition in both peanut and cotton strips of the top soil whereas the bacterial diversity was barely affected compared with MP and MC. At blossom-needling stage, the metabolic functional features of the bacterial communities such as fatty acid biosynthesis, lipoic acid metabolism, peptidoglycan biosynthesis, and biosynthesis of ansamycins were significantly enriched in MP compared with other treatments. Conversely, these metabolic functional features were dramatically depleted in MP while significantly enriched in IC at podding stage. Permeable root barrier treatments (NC-P and NC-C) counteracted the benefits of IC and the side effects were more pronounced in impermeable treatments (SC-P and SC-C).

Conclusion

Peanut/cotton intercropping increases crop yield as well as economic returns under non-saline, secondary-saline, and coastal saline soil conditions probably by modulating the soil bacterial abundance composition and accelerating plant nutrients accumulation.
Assessment of the diagnostic value of serum ceruloplasmin for Wilson’s disease in children
Authors: Lu Xinshuo , Li Simin , Zhang Wen , Lin Yunting , Lu Zhikun , Cai Yanna , Su Xueying , Shao Yongxian , Liu Zongcai , Sheng Huiying , Huang Yonglan , Liu Li , Zeng Chunhua
Published: March 2022

Background

Serum ceruloplasmin is one of the major diagnostic parameters for Wilson’s disease (WD). Age and gender difference of serum ceruloplasmin remain controversy. This study aims to assess diagnostic value of serum ceruloplasmin level for WD in children up to age of 15 years.

Methods

Serum ceruloplasmin levels were measured in 317 WD patients, 21 heterozygotes, 372 healthy control children and 154 non-WD patients with other liver diseases. Receiver operating characteristic (ROC) curve was used to determine the diagnostic accuracy of serum ceruloplasmin for WD in children.

Results

Among healthy controls, serum ceruloplasmin level was slightly low in the infants younger than 6 months, and then maintained from 26 to 33 mg/dl after age of 6 months. A total of 8.1% of healthy children had levels of serum ceruloplasmin < 20 mg/dL. Serum ceruloplasmin level was 5.7 ± 4.7 mg/dl in WD patients, and 25.6 ± 5.9 mg/dl in heterozygous carriers. Only 1.9% of WD patients had serum ceruloplasmin levels > 20 mg/dL. Serum ceruloplasmin levels had gender difference, being higher in healthy boys than healthy girls, and higher in asymptomatic WD boys than asymptomatic WD girls (p < 0.01,p < 0.05). Serum ceruloplasmin levels also presented genotypic difference. WD patients with R778L homozygotes exhibited lower levels of serum ceruloplasmin than the patients without R778L (p < 0.05). The ROC curve revealed that serum ceruloplasmin level, at a cutoff value of 16.8 mg/dL, had the highest AUC value (0.990) with a sensitivity of 95.9% and a specificity of 93.6%.

Conclusions

Serum ceruloplasmin is one of sensitive diagnostic biomarkers for WD in children. Gender and genotypic difference of serum ceruloplasmin level should be considered. The cutoff value of serum ceruloplasmin level < 16.8 mg/dL may provide the highest accuracy for diagnosis of WD in children.
Association between dietary protein intake and changes in health-related quality of life in older adults: findings from the AusDiab 12-year prospective study
Authors: Matison Annabel P. , Milte Catherine M. , Shaw Jonathan E. , Magliano Dianna J. , Daly Robin M. , Torres Susan J.
Published: March 2022

Background

Adequate dietary protein intake is recommended for older adults to optimise muscle health and function, and support recovery from illness, however, its effect on health-related quality of life (HRQoL) is unclear. The aim of this study was to examine the association between total protein intake and different sources of dietary protein and HRQoL in Australians aged 60 years and older over a 12-year period.

Methods

This study used data from the Australian Diabetes, Obesity and Lifestyle study (AusDiab), a 12-year population-based prospective study. The sample included 752 (386 females) adults aged 60 years and older. Protein intake was estimated at baseline (1999/2000) from a 74-item Food Frequency Questionnaire, and HRQoL using the 36-item Short-form Health Survey assessed at baseline (1999/2000) and after 12 years (2011/12). The association between protein intake and change in HRQoL was evaluated using multivariate regression analysis adjusted for relevant confounders. The difference in change in HRQoL between participants with total protein intakes of < 1.0 g/kg/day, intakes of between 1.0–1.2 g/kg/day and intakes of > 1.2 g/kg/day were assessed using one-way ANCOVA.

Results

Total protein intake at baseline was not associated with 12-year changes in physical component summary (PCS) or mental component summary (MCS) scores of HRQoL. Higher animal, red meat and processed animal protein intakes were associated with deteriorations in PCS scores after adjusting for relevant confounders (β = − 0.04; 95% CI: − 0.07, −0.01 ; p = 0.009; β = − 0.05; 95% CI: − 0.08, − 0.01; p = 0.018; β = − 0.17; 95% CI: − 0.31, − 0.02; p = 0.027 respectively). Higher red meat protein intake was associated with deteriorations in MCS scores after adjusting for relevant confounders (β = − 0.04; 95% CI: − 0.08, − 0.01; p = 0.011). There was no difference in 12-year changes in PCS or MCS between participants consuming total protein of < 1.0 g/kg/day, 1.0–1.2 g/kg/day and intakes of > 1.2 g/kg/day.

Conclusion

There was no relationship between total dietary protein intake and HRQoL, but higher protein intakes from animal, red meat and processed animal sources were associated with a deterioration in HRQoL scores over 12 years. Due to the number of associations examined and high drop out of older less healthy participants, further research is required to confirm the associations detected in healthy and less healthy participants, with a view to making protein intake recommendations for older adults.
Family caregivers’ perspectives on their interaction and relationship with people living with dementia in a nursing home: a qualitative study
Authors: van Corven Charlotte T. M. , Bielderman Annemiek , Lucassen Peter L. B. J. , Verbeek Hilde , Lesman-Leegte Ivonne , Depla Marja F. I. A. , Stoop Annerieke , Graff Maud J. L. , Gerritsen Debby L.
Published: March 2022

Background

Social interactions are important for people living with dementia in a nursing home. However, not much is known about interactions and relationships between residents and family caregivers and related experiences of family caregivers. We aim to advance the knowledge on how family caregivers interact with people living with dementia in a nursing home and how they maintain or redesign a meaningful connection.

Methods

Qualitative research using interviews with family caregivers (n = 31) to explore perspectives on their interaction and relationship with the person living with dementia. Interviews were held during the reopening of nursing homes after the first COVID-19 lockdown in the Netherlands. In this situation, family caregivers became more aware of their interaction and relationship with the resident, which provided a unique opportunity to reflect on this. The interviews explored the interaction and relationship in a broad sense, not specifically for the COVID-19 situation. Thematic analysis was performed to analyze the data.

Results

We were able to identify three key themes reflecting the experiences of family caregivers: (1) changes in the interaction and relationship, (2) strategies to promote connection, and (3) appreciation of the interaction and relationship. From the viewpoint of family caregivers, the interaction and relationship are important for both the resident living with dementia and for themselves, and family caregivers have different strategies for establishing a meaningful connection. Nevertheless, some appear to experience difficulties with constructing such a connection with the resident.

Conclusions

Our results provide a basis for supporting family caregivers in perceiving and establishing mutuality and reciprocity so that they can experience togetherness.
Neonatal outcome in vaginal breech labor at 32 + 0—36 + 0 weeks of gestation: a nationwide, population-based record linkage study
Authors: Toijonen Anna , Heinonen Seppo , Gissler Mika , Macharey Georg
Published: March 2022

Background

In many countries, vaginal breech labor at term is an option in selected cases. However, the safety of vaginal breech labor in preterm is still unclear. Therefore our study aimed to evaluate the safety of vaginal breech labor in late preterm deliveries.

Design

A retrospective register-based study.

Setting

Maternity hospitals in Finland, 2004–2017.

Participants

The study population included 762 preterm breech deliveries at 32 + 0—36 + 6 gestational weeks according to the mode of delivery, 535 (70.2%) of them were born vaginally in breech presentation, and 227 (29.8%) were delivered by non-urgent cesarean section.

Methods

The study compared short-term neonatal adverse outcomes of singleton vaginal breech deliveries with non-urgent cesarean deliveries at 32 + 0 to 36 + 6 weeks of gestation. An odd ratio with 95% confidence intervals was calculated to estimate the relative risk of adverse outcomes.

Outcome measures

Neonatal death, an arterial umbilical pH below seven, a five-minute Apgar score below four and seven, admission to neonatal intensive care unit, neonatal intubation, neonatal antibiotic therapy, neonatal birth trauma, respiratory distress syndrome, neonatal convulsions, cerebral ischemia, hypoxic-ischemic encephalopathy, congenital hypotonia, and a composite of severe adverse outcomes.

Results

A five-minute Apgar scores below seven were increased in vaginal breech labor at 32 + 0 to 36 + 6 weeks of gestation compared to non-urgent cesarean sections (aOR 2.48, 95% CI 1.08–5.59). Neonatal antibiotic therapy, the admission to neonatal intensive care unit, and neonatal respiratory distress syndrome were decreased after vaginal breech labor compared to the outcomes of non-urgent cesarean section (neonatal antibiotic therapy aOR 0.60, 95% CI 0.40–0.89; neonatal NICU admission aOR 0.47, 95% CI 0.33–0.68; respiratory distress syndrome aOR 0.30, 95% CI 0.19–0.48).

Conclusion

Vaginal breech labor at 32 + 0—36 + 6 gestational weeks does not increase severe neonatal short-term morbidity or mortality compared to cesarean section.
New method for determining breast cancer recurrence-free survival using routinely collected real-world health data
Authors: Jung Hyunmin , Lu Mingshan , Quan May Lynn , Cheung Winson Y. , Kong Shiying , Lupichuk Sasha , Feng Yuanchao , Xu Yuan
Published: March 2022

Background

In cancer survival analyses using population-based data, researchers face the challenge of ascertaining the timing of recurrence. We previously developed algorithms to identify recurrence of breast cancer. This is a follow-up study to detect the timing of recurrence.

Methods

Health events that signified recurrence and timing were obtained from routinely collected administrative data. The timing of recurrence was estimated by finding the timing of key indicator events using three different algorithms, respectively. For validation, we compared algorithm-estimated timing of recurrence with that obtained from chart-reviewed data. We further compared the results of cox regressions models (modeling recurrence-free survival) based on the algorithms versus chart review.

Results

In total, 598 breast cancer patients were included. 121 (20.2%) had recurrence after a median follow-up of 4 years. Based on the high accuracy algorithm for identifying the presence of recurrence (with 94.2% sensitivity and 79.2% positive predictive value), the majority (64.5%) of the algorithm-estimated recurrence dates fell within 3 months of the corresponding chart review determined recurrence dates. The algorithm estimated and chart-reviewed data generated Kaplan–Meier (K-M) curves and Cox regression results for recurrence-free survival (hazard ratios and P-values) were very similar.

Conclusion

The proposed algorithms for identifying the timing of breast cancer recurrence achieved similar results to the chart review data and were potentially useful in survival analysis.
Chrysoeriol suppresses hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes and inhibits JAK2/STAT3 signaling
Authors: Wu Jia-Ying , Chen Ying-Jie , Fu Xiu-Qiong , Li Jun-Kui , Chou Ji-Yao , Yin Cheng-Le , Bai Jing-Xuan , Wu Ying , Wang Xiao-Qi , Li Amy Sze-man , Wong Lut Yi , Yu Zhi-Ling
Published: March 2022

Background

Fibroblast-like synoviocytes (FLS) have cancer cell-like characteristics, such as abnormal proliferation and resistance to apoptosis, and play a pathogenic role in rheumatoid arthritis (RA). Hyperproliferation of RA-FLS that can be triggered by the activation of interleukin-6/signal transducer and activator of transcription 3 (IL-6/STAT3) signaling destructs cartilage and bone in RA patients. Chrysoeriol is a flavone found in medicinal herbs such as Chrysanthemi Indici Flos (the dried capitulum of Chrysanthemum indicum L.). These herbs are commonly used in treating RA. Chrysoeriol has been shown to exert anti-inflammatory effects and inhibit STAT3 signaling in our previous studies. This study aimed to determine whether chrysoeriol inhibits hyperproliferation of RA-FLS, and whether inhibiting STAT3 signaling is one of the underlying mechanisms.

Methods

IL-6/soluble IL-6 receptor (IL-6/sIL-6R)-stimulated RA-FLS were used to evaluate the effects of chrysoeriol. CCK-8 assay and crystal violet staining were used to examine cell proliferation. Annexin V-FITC/PI double staining was used to detect cell apoptosis. Western blotting was employed to determine protein levels.

Results

Chrysoeriol suppressed hyperproliferation of, and evoked apoptosis in, IL-6/sIL-6R-stimulated RA-FLS. The apoptotic effect of chrysoeriol was verified by its ability to cleave caspase-3 and caspase-9. Mechanistic studies revealed that chrysoeriol inhibited activation/phosphorylation of Janus kinase 2 (JAK2, Tyr1007/1008) and STAT3 (Tyr705); decreased STAT3 nuclear level and down-regulated protein levels of Bcl-2 and Mcl-1 that are transcriptionally regulated by STAT3. Over-activation of STAT3 significantly diminished anti-proliferative effects of chrysoeriol in IL-6/sIL-6R-stimulated RA-FLS.

Conclusions

We for the first time demonstrated that chrysoeriol suppresses hyperproliferation of RA-FLS, and suppression of JAK2/STAT3 signaling contributes to the underlying mechanisms. This study provides pharmacological and chemical justifications for the traditional use of chrysoeriol-containing herbs in treating RA, and provides a pharmacological basis for developing chrysoeriol into a novel anti-RA agent.
Evaluation of the integration of social accountability values into medical education using a problem-based learning curriculum
Authors: Dash Nihar Ranjan , Taha Mohamed H. , Shorbagi Sarra , Abdalla Mohamed Elhassan
Published: March 2022

Background

Medical schools have the obligation to direct their education toward addressing the priority health concerns of the societies that they serve. The purpose of this study was to evaluate the integration of the concepts and values of social accountability into the case scenarios that are used in a problem-based learning (PBL) curriculum at a medical school in the United Arab Emirates (UAE).

Methods

A validated “social accountability inventory for PBL” was used for examining 70 case scenarios in a problem-based learning (PBL) medical curriculum.

Results

The findings of the study showed that patient gender and age were included in all the 70 case scenarios. Vast majority of the case scenarios had successfully integrated the social accountably values in addressing the following: the major health problems or social health concerns of the UAE (73%), the social determinants of health (70%), the contextual integration of medical professionalism (87%), the evolving roles of doctors in the health system (79%), the healthcare referral system based on the case complexity (73%), the involvement of different stakeholders in healthcare (87%), psychosocial issues rather than only the disease-oriented issues (80%) and the values of health promotion/prevention (59%) cases. On the other hand, the case scenarios were deficient in integrating other social accountability values that related to the importance of treatment cost-effectiveness (91%), consideration of the underserved, disadvantaged or vulnerable populations in the society (89%), patient’s ethnicity (77%), multidisciplinary approach to patient management (67%), the socioeconomic statuses of patients (53%), the issues regarding the management of the health system (39%) respectively. There was variability in integrating the social accountability values in case scenarios across different units which are based on organ system.

Conclusion

Medical educators and healthcare leaders can use this valuable data to calibrate the curriculum content, especially when using a problem-based learning curriculum to integrate the values of social accountability such as relevance, quality, equity and cost-effectiveness to train the future generation of healthcare providers to be ready to address the ever-changing and diverse needs of the societies.
Targeting the RNA m6A modification for cancer immunotherapy
Authors: Li Xinxin , Ma Shoubao , Deng Youcai , Yi Ping , Yu Jianhua
Published: March 2022

N6-methyladenosine (m6A) is the most abundant epigenetic modification of RNA, and its dysregulation drives aberrant transcription and translation programs that promote cancer occurrence and progression. Although defective gene regulation resulting from m6A often affects oncogenic and tumor-suppressing networks, m6A can also modulate tumor immunogenicity and immune cells involved in anti-tumor responses. Understanding this counterintuitive concept can aid the design of new drugs that target m6A to potentially improve the outcomes of cancer immunotherapies. Here, we provide an up-to-date and comprehensive overview of how m6A modifications intrinsically affect immune cells and how alterations in tumor cell m6A modifications extrinsically affect immune cell responses in the tumor microenvironment (TME). We also review strategies for modulating endogenous anti-tumor immunity and discuss the challenge of reshaping the TME. Strategies include: combining specific and efficient inhibitors against m6A regulators with immune checkpoint blockers; generating an effective programmable m6A gene-editing system that enables efficient manipulation of individual m6A sites; establishing an effective m6A modification system to enhance anti-tumor immune responses in T cells or natural killer cells; and using nanoparticles that specifically target tumor-associated macrophages (TAMs) to deliver messenger RNA or small interfering RNA of m6A-related molecules that repolarize TAMs, enabling them to remodel the TME. The goal of this review is to help the field understand how m6A modifications intrinsically and extrinsically shape immune responses in the TME so that better cancer immunotherapy can be designed and developed.
Computer-assisted three-dimensional quantitation of programmed death-ligand 1 in non-small cell lung cancer using tissue clearing technology
Authors: Lin Yen-Yu , Wang Lei-Chi , Hsieh Yu-Han , Hung Yu-Ling , Chen Yung-An , Lin Yu-Chieh , Lin Yen-Yin , Chou Teh-Ying
Published: March 2022

Immune checkpoint blockade therapy has revolutionized non-small cell lung cancer treatment. However, not all patients respond to this therapy. Assessing the tumor expression of immune checkpoint molecules, including programmed death-ligand 1 (PD-L1), is the current standard in predicting treatment response. However, the correlation between PD-L1 expression and anti-PD-1/PD-L1 treatment response is not perfect. This is partly caused by tumor heterogeneity and the common practice of assessing PD-L1 expression based on limited biopsy material. To overcome this problem, we developed a novel method that can make formalin-fixed, paraffin-embedded tissue translucent, allowing three-dimensional (3D) imaging. Our protocol can process tissues up to 150 μm in thickness, allowing anti-PD-L1 staining of the entire tissue and producing high resolution 3D images. Compared to a traditional 4 μm section, our 3D image provides 30 times more coverage of the specimen, assessing PD-L1 expression of approximately 10 times more cells. We further developed a computer-assisted PD-L1 quantitation method to analyze these images, and we found marked variation of PD-L1 expression in 3D. In 5 of 33 needle-biopsy-sized specimens (15.2%), the PD-L1 tumor proportion score (TPS) varied by greater than 10% at different depth levels. In 14 cases (42.4%), the TPS at different depth levels fell into different categories (< 1%, 1–49%, or ≥ 50%), which can potentially influence treatment decisions. Importantly, our technology permits recovery of the processed tissue for subsequent analysis, including histology examination, immunohistochemistry, and mutation analysis. In conclusion, our novel method has the potential to increase the accuracy of tumor PD-L1 expression assessment and enable precise deployment of cancer immunotherapy.
Design and implementation of a novel pharmacogenetic assay for the identification of the CYP2D6*10 genetic variant
Authors: Ranadeva Nadeeka Dimuthu Kumari , Sirisena Nirmala Dushyanthi , Wetthasinghe Tithila Kalum , Noordeen Nafeesa , Dissanayake Vajira Harshadeva Weerabaddana
Published: March 2022

Objectives

Tamoxifen is considered to be the most widely used adjuvant therapy for hormone receptor positive breast cancer in premenopausal women. However, it is reported that nearly 30% of patients receiving tamoxifen therapy have shown reduced or no benefits. This may be due to the high inter-individual variations in the CYP2D6 gene that is involved in tamoxifen metabolism. The CYP2D6*10 gene variant (rs1065852C>T) is reported to be commonly found in Asian and South Asian populations. The present study was undertaken to design a novel pharmacogenetic assay (Single step-Tetra Arms Polymerase Chain Reaction) for the identification of the CYP2D6*10 variant and implement the designed assay by genotyping a cohort of breast cancer patients.

Results

The novel assay was successfully designed, optimized and validated using Sanger sequencing. Blood samples from 70 patients were genotyped. The following bands were observed in the gel image: Control band at 454 bp; band for C allele at 195 bp; band for T allele at 300 bp. The genotype frequencies for the CYP2D6*10 (rs1065852C>T) variant were: CC-24.28% (17/70), CT-75.71% (53/70), TT-0% (0/70). The allele frequencies were: T-allele-37.86% and C-allele-62.14%.
Community and cultural engagement for people with lived experience of mental health conditions: what are the barriers and enablers?
Authors: Baxter Louise , Burton Alexandra , Fancourt Daisy
Published: March 2022

Background

Community and cultural engagement can support recovery, help symptom management and increase social connections for people with lived experience of mental health conditions. However, research suggests that people with mental health conditions experience significant barriers to participation. The aim of this study was to explore barriers and enablers of participation in community and cultural activities among people with mental health conditions.

Methods

A qualitative interview study with 23 people with mild-to-moderate mental health conditions was undertaken. Data were analysed thematically, and themes were mapped to domains of the Capability, Opportunity and Motivation Model of Behaviour (COM-B).

Results

Eleven themes were identified from the analysis. Three themes involved participant Capability: physical skills, psychological traits and physical health limitations and three themes related to Opportunity: affordability and accessibility, structure and nature of the group, and support from others to attend. Five themes mapped to Motivation: creative identity, recovery and coping, enjoyment and fun, connecting with others, and information and planning. Participants were motivated to engage with community and cultural activities through “a creative identity”, belief that engagement would help recovery from mental illness, and a desire to connect with others and make friends. Motivation to participate was sustained by the enjoyable nature of activities. However, participants’ ability to engage was hampered by the expense, inaccessibility and sometimes unstructured nature of activities, and social anxiety associated with attending. Some participants had physical limitations such as fatigue or physical health problems to overcome. Interventions that could address these barriers include peer support, training for social prescribers to account for identity and previous experiences of participation, training for community organisations in providing a welcoming and structured environment, and provision of long-term sustainable funding to community organisations to subsidise attendance, transport or equipment costs.

Conclusion

People with mental health conditions may be at risk of experiencing barriers to community and cultural engagement due to existing social inequalities and social anxiety, however believing that involvement will support mental health was an enabler to participation. Future studies are needed to test the effectiveness of potential interventions to address the barriers and harness the facilitators identified here, to enable a more socially inclusive community and voluntary sector, and a potentially more responsive and effective social prescribing service in the UK for people experiencing mental health problems.
The role of DHCR24 in the pathogenesis of AD: re-cognition of the relationship between cholesterol and AD pathogenesis
Authors: Bai Xiaojing , Mai Meiting , Yao Kai , Zhang Mengqi , Huang Yue , Zhang Wenbin , Guo Xiaorou , Xu Yixuan , Zhang Ying , Qurban Atikam , Duan Lijie , Bu Jimei , Zhang Jianfeng , Wu Junfeng , Zhao Yongfei , Yuan Xiangshan , Zu Hengbing
Published: March 2022

Previous studies show that 3β-hydroxysterol-Δ24 reductase (DHCR24) has a remarked decline in the brain of AD patients. In brain cholesterol synthetic metabolism, DHCR24 is known as the heavily key synthetase in cholesterol synthesis. Moreover, mutations of DHCR24 gene result in inhibition of the enzymatic activity of DHCR24, causing brain cholesterol deficiency and desmosterol accumulation. Furthermore, in vitro studies also demonstrated that DHCR24 knockdown lead to the inhibition of cholesterol synthesis, and the decrease of plasma membrane cholesterol and intracellular cholesterol level. Obviously, DHCR24 could play a crucial role in maintaining cholesterol homeostasis via the control of cholesterol synthesis. Over the past two decades, accumulating data suggests that DHCR24 activity is downregulated by major risk factors for AD, suggesting a potential link between DHCR24 downregulation and AD pathogenesis. Thus, the brain cholesterol loss seems to be induced by the major risk factors for AD, suggesting a possible causative link between brain cholesterol loss and AD. According to previous data and our study, we further found that the reduced cholesterol level in plasma membrane and intracellular compartments by the deficiency of DHCR24 activity obviously was involved in β-amyloid generation, tau hyperphosphorylation, apoptosis. Importantly, increasing evidences reveal that the brain cholesterol loss and lipid raft disorganization are obviously linked toneuropathologicalimpairments which are associated with AD pathogenesis. Therefore, based on previous data and research on DHCR24, we suppose that the brain cholesterol deficiency/loss might be involved in the pathogenesis of AD.
Progressive multifocal fibrosing neuropathy: description of a novel disease
Authors: Mendoza Fabian A. , Bagley Jennifer , Gochfeld Michael , Dalakas Marinos C. , Farber John L. , Jimenez Sergio A.
Published: March 2022

Entrapment peripheral neuropathies are clinically characterized by sensory impairment and motor deficits. They are usually caused by mechanical injuries, but they are also a frequent manifestation of metabolic diseases, toxic agent exposure, or systemic fibrotic disorders. Here we describe the clinical, radiological, and histopathological features of a novel progressive fibrotic disorder characterized by progressive multifocal fibrosing neuropathy. We identified two patients who presented with severe and progressive peripheral neuropathic symptoms sequentially affecting multiple sites. These patients presented with severe and progressive multifocal, sequentially additive peripheral neuropathic symptoms. Extensive nerve conduction and radiological studies showed the sequential development of multifocal motor and sensory peripheral neuropathy in the absence of any exposure to known infectious, inflammatory, or fibrotic triggers and the lack of family history of compression neuropathies. Extensive clinical and laboratory test evaluation failed to support the diagnosis of any primary inflammatory or genetic peripheral neuropathy and there was no evidence of any systemic fibrosing disorder including Systemic Sclerosis, lacking cutaneous fibrotic changes and cardiopulmonary abnormalities. The clinical course was progressive with sequential development of motor and sensory deficits of upper and lower extremities displaying proximal predominance. Histopathological study of tissues obtained during nerve release surgeries showed severe perineural fibrosis with marked accumulation of thick collagen bundles encroaching the peripheral nerves. There was no evidence of vasculitic, inflammatory, or vascular fibroproliferative lesions. We suggest that the clinical findings described here represent a previously undescribed fibrotic disorder affecting peripheral nerves, and we propose the descriptive term "Progressive Multifocal Fibrosing Neuropathy" to refer to this novel disorder. Despite the inherent limitations of this early description, we hope this is would contribute to the identification of additional cases.
Microglia phenotypes are associated with subregional patterns of concomitant tau, amyloid-β and α-synuclein pathologies in the hippocampus of patients with Alzheimer’s disease and dementia with Lewy bodies
Authors: Fixemer Sonja , Ameli Corrado , Hammer Gaël , Salamanca Luis , Uriarte Huarte Oihane , Schwartz Chantal , Gérardy Jean-Jacques , Mechawar Naguib , Skupin Alexander , Mittelbronn Michel , Bouvier David S.
Published: March 2022

The cellular alterations of the hippocampus lead to memory decline, a shared symptom between Alzheimer’s disease (AD) and dementia with Lewy Bodies (DLB) patients. However, the subregional deterioration pattern of the hippocampus differs between AD and DLB with the CA1 subfield being more severely affected in AD. The activation of microglia, the brain immune cells, could play a role in its selective volume loss. How subregional microglia populations vary within AD or DLB and across these conditions remains poorly understood. Furthermore, how the nature of the hippocampal local pathological imprint is associated with microglia responses needs to be elucidated. To this purpose, we employed an automated pipeline for analysis of 3D confocal microscopy images to assess CA1, CA3 and DG/CA4 subfields microglia responses in post-mortem hippocampal samples from late-onset AD (n = 10), DLB (n = 8) and age-matched control (CTL) (n = 11) individuals. In parallel, we performed volumetric analyses of hyperphosphorylated tau (pTau), amyloid-β (Aβ) and phosphorylated α-synuclein (pSyn) loads. For each of the 32,447 extracted microglia, 16 morphological features were measured to classify them into seven distinct morphological clusters. Our results show similar alterations of microglial morphological features and clusters in AD and DLB, but with more prominent changes in AD. We identified two distinct microglia clusters enriched in disease conditions and particularly increased in CA1 and DG/CA4 of AD and CA3 of DLB. Our study confirms frequent concomitance of pTau, Aβ and pSyn loads across AD and DLB but reveals a specific subregional pattern for each type of pathology, along with a generally increased severity in AD. Furthermore, pTau and pSyn loads were highly correlated across subregions and conditions. We uncovered tight associations between microglial changes and the subfield pathological imprint. Our findings suggest that combinations and severity of subregional pTau, Aβ and pSyn pathologies transform local microglia phenotypic composition in the hippocampus. The high burdens of pTau and pSyn associated with increased microglial alterations could be a factor in CA1 vulnerability in AD.
Prostate MRI using a rigid two-channel phased-array endorectal coil: comparison with phased array coil acquisition at 3 T
Authors: Lewis Sara , Ganti Aasrith , Argiriadi Pamela , Rosen Ally , Hectors Stefanie , Semaan Sahar , Song Christopher , Peti Steve , Segall Maxwell , George Kezia , Jaikaran Vaneela , Villa Sebastian , Kestenbaum David , Voutsinas Nicholas , Doucette John , Tewari Ashutosh , Rastinehad Ardeshir R. , Taouli Bachir
Published: March 2022

Background

To compare image quality, lesion detection and patient comfort of 3T prostate MRI using a combined rigid two-channel phased-array endorectal coil and an external phased-array coil (ERC-PAC) compared to external PAC acquisition in the same patients.

Methods

Thirty three men (mean age 65.3y) with suspected (n = 15) or biopsy-proven prostate cancer (PCa, n = 18) were prospectively enrolled in this exploratory study. 3T prostate MRI including T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) was performed using an ERC-PAC versus PAC alone, in random order. Image quality, lesion detection and characterization (biparametric PI-RADSv2.1) were evaluated by 2 independent observers. Estimated signal-to-noise ratio (eSNR) was measured in identified lesions and the peripheral zone (PZ). Patient comfort was assessed using a questionnaire. Data were compared between sequences and acquisitions. Inter/intra-observer agreement for PI-RADS scores was evaluated.

Results

Twenty four prostate lesions (22 PCa) were identified in 20/33 men. Superior image quality was found for ERC-PAC compared to PAC for T2WI for one observer (Obs.1, p < 0.03) and high b-value DWI for both observers (p < 0.05). The sensitivity of PI-RADS for lesion detection for ERC-PAC and PAC acquisitions was 79.2 and 75% for Obs.1, and 79.1 and 66.7%, for Obs.2, without significant difference for each observer (McNemar p-values ≥0.08). Inter−/intra-observer agreement for PI-RADS scores was moderate-to-substantial (kappa = 0.52–0.84). Higher eSNR was observed for lesions and PZ for T2WI and PZ for DWI using ERC-PAC (p < 0.013). Most patients (21/33) reported discomfort at ERC insertion.

Conclusion

Despite improved image quality and eSNR using the rigid ERC-PAC combination, no significant improvement in lesion detection was observed, therefore not supporting the routine use of ERC for prostate MRI.
The influence of epidural volume extension on spinal block with hyperbaric bupivacaine for elective knee arthroplasty
Authors: Özeroğlu Ertaç , Yilmaz Fulya
Published: March 2022

Background

Epidural volume extension (EVE) via a combined spinal–epidural is the enhancement of a small-dose intrathecal block by an epidural injection of physiological saline solution. The aim of this study was to investigate the sensory and motor block characteristics of spinal anesthesia after EVE. Eighty patients enrolled in this prospective, randomized, double-blind study. Group I (n=40) received 10 mg hyperbaric bupivacaine and group II (n=40) first received 10 mg hyperbaric bupivacaine intrathecally and subsequently 10 mL saline via epidural catheter.

Results

In the first 30 min after combined spinal–epidural anesthesia, the maximum sensory block level was significantly higher in group II than in group I. The Bromage score was significantly higher in group II than in group I at 3–6 and 9 min of the intraoperative period. EVE increased the mean Smax significantly in group 2 than group 1 (p<0.05). Tmax was statistically similar between group 1 and group 2 (p>0.05). EVE significantly altered Time10 and Tadeq in group 2 (p<0.05).

Conclusions

EVE with saline (10 mL) offer early onset of sensory and motor block and a high level of sensory block. And also delay supplemental epidural dose requirement intraoperatively.
Vitamin D receptor gene polymorphism in Madura pregnant women with hypertension: a case control study
Authors: Setiarsih Dini , Hastuti Pramudji , Nurdiati Detty Siti
Published: March 2022

Background

Genetic factors are important considerations in the etiology of preeclampsia and gestational hypertension. Several previous studies have shown an association of Vitamin D receptor (VDR) gene polymorphisms with hypertension in pregnancy. However, the number of studies is still very limited and the results differ from one another.

Aim of the study

This study aimed to analyze the polymorphisms of rs2228570 and rs731236 of the VDR gene in subjects with hypertension and non-hypertension in pregnancy in Madura ethnicity.

Subjects and methods

The researchers conducted tests for two polymorphisms in the VDR gene among 210 subjects consisting of 105 pregnant women with hypertension and 105 non-hypertension pregnant women from Madura ethnicity. The rs2228570 (T>C) and rs731236 (C>T) polymorphisms were detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism. All data were analyzed by T-tests and Chi-Square tests.

Results

The TT genotype frequency of rs2228570 (15.2%) in the hypertension group was higher than in the control group (6.7%) (p = 0.047). Subjects with the TT genotype at rs2228570 showed a 3.048 times greater risk of developing hypertension than the CC genotype (OR = 3.048: 1.135–8.183, p = 0.023). The T allele frequency of rs2228570 (40.5%) in the hypertension group was higher than in the control group (30.5%) (p = 0.032). Subjects with the T allele had 1.551 times greater risk of developing hypertension. There was no significant difference in genotype and allele of rs731236 between hypertension subjects and controls.

Conclusion

The TT genotype and T allele of rs2228570 in the hypertension group were risk factors for hypertension in this study. While the TT genotype and T allele at rs731236 were not risk factors for hypertension in pregnancy. Genotyping of VDR gene polymorphisms in pregnant women is expected to be useful in strategies for treating hypertension in pregnancy.
Applying implementation science frameworks to identify factors that influence the intention of healthcare providers to offer PrEP care and advocate for PrEP in HIV clinics in Colombia: a cross-sectional study
Authors: Martinez-Cajas Jorge Luis , Torres Julian , Mueses Hector Fabio , Plazas Pilar Camargo , Arrivillaga Marcela , Gomez Sheila Andrea , Galindo Ximena , Buitrago Ernesto Martinez , Llano Beatriz Eugenia Alvarado
Published: March 2022

Background

Few studies have used implementation science frameworks to identify determinants of PrEP prescription by healthcare providers. In this work, we developed and psychometrically examined a questionnaire using the theoretical domains framework (TDF) and the consolidated framework for implementation research (CFIR). We used this questionnaire to investigate what factors influence the intention of healthcare providers to offer PrEP care and advocate for PrEP.

Methods

We conducted a cross-sectional study in 16 HIV healthcare organizations in Colombia. A 98-item questionnaire was administered online to 129 healthcare professionals. One hundred had complete data for this analysis. We used exploratory factor analysis to assess the psychometric properties of both frameworks, and multinomial regression analysis to evaluate the associations of the frameworks’ domains with two outcomes: (1) intention to offer PrEP care and (2) intention to advocate for PrEP impmentation.

Results

We found support for nine indices with good internal consistency, reflecting PrEP characteristics, attitudes towards population needs, concerns about the use of PrEP, concerns about the role of the healthcare systems, knowledge, beliefs about capabilities, professional role, social influence, and beliefs about consequences. Notably, only 57% of the participants were likely to have a plan to care for people in PrEP and 66.7% were likely to advocate for PrEP. The perception of the need for PrEP in populations, the value of PrEP as a practice, the influence of colleagues, and seeing PrEP care as a priority was related to being less likely to be unwilling to provide or advocate for PrEP care.

Conclusion

Our findings suggested the importance of multilevel strategies to increase the provision of PrEP care by healthcare providers including adquisition of new skills, training of PrEP champions, and strength the capacity of the health system.