bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobile health to promote physical activity in people post stroke or transient ischemic attack – study protocol for a feasibility randomised controlled trial
Authors: Thurston Charlotte , Bezuidenhout Lucian , Humphries Sophia , Johansson Sverker , von Koch Lena , Häger Charlotte K. , Holmlund Lisa , Sundberg Carl Johan , Garcia-Ptacek Sara , Kwak Lydia , Nilsson Michael , English Coralie , Conradsson David Moulaee 
Published: March 2023

Abstract
Background
Physical activity is essential to improve health and reduce the risk of recurrence of stroke or transient ischemic attack (TIA). Still, people post stroke or TIA are often physically inactive and the availability of physical activity promotion services are often limited. This study builds on an existing Australian telehealth-delivered programme (i-REBOUND– Let’s get moving) which provides support for home-based physical activity for people post stroke or TIA. The aim of this study is to test the feasibility, acceptability, and preliminary effects of a mobile Health (mHealth) version of the i-REBOUND programme for the promotion of physical activity in people post stroke or TIA living in Sweden.

Methods
One hundred and twenty participants with stroke or TIA will be recruited via advertisement. A parallel-group feasibility randomised controlled trial design with a 1:1 allocation ratio to 1) i-REBOUND programme receiving physical exercise and support for sustained engagement in physical activity through behavioural change techniques, or 2) behavioural change techniques for physical activity. Both interventions will proceed for six months and be delivered digitally through a mobile app. The feasibility outcomes (i.e., reach, adherence, safety and fidelity) will be monitored throughout the study. Acceptability will be assessed using the Telehealth Usability Questionnaire and further explored through qualitative interviews with a subset of both study participants and the physiotherapists delivering the intervention. Clinical outcomes on preliminary effects of the intervention will include blood pressure, engagement in physical activity, self-perceived exercise self-efficacy, fatigue, depression, anxiety, stress and health-related quality of life and will be measured at baseline and at 3, 6 and 12 months after the baseline assessments.

Discussion
We hypothesise that the mHealth delivery of the i-REBOUND programme will be feasible and acceptable in people post stroke/TIA living in rural and urban regions of Sweden. The results of this feasibility trial will inform the development of full-scale and appropriately powered trial to test the effects and costs of mHealth delivered physical activity for people after stroke or TIA.

Trial registration
ClinicalTrials.gov Identifier: NCT05111951. Registered November 8, 2021.
Deprescribing psychotropic medicines for behaviours that challenge in people with intellectual disabilities: a systematic review
Authors: Adams Danielle , Hastings Richard P. , Maidment Ian , Shah Chetan , Langdon Peter E. 
Published: March 2023

Abstract
Background
Clear evidence of overprescribing of psychotropic medicines to manage behaviours that challenges in people with intellectual disabilities has led to national programmes within the U.K. such as NHS England’s STOMP to address this. The focus of the intervention in our review was deprescribing of psychotropic medicines in children and adults with intellectual disabilities. Mental health symptomatology and quality of life were main outcomes.

Methods
We reviewed the evidence using databases Medline, Embase, PsycINFO, Web of Science, CINAHL and Open Grey with an initial cut-off date of 22nd August 2020 and an update on 14th March 2022. The first reviewer (DA) extracted data using a bespoke form and appraised study quality using CASP and Murad tools. The second reviewer (CS) independently assessed a random 20% of papers.

Results
Database searching identified 8675 records with 54 studies included in the final analysis.
The narrative synthesis suggests that psychotropic medicines can sometimes be deprescribed. Positive and negative consequences were reported. Positive effects on behaviour, mental and physical health were associated with an interdisciplinary model.

Conclusions
This is the first systematic review of the effects of deprescribing psychotropic medicines in people with intellectual disabilities which is not limited to antipsychotics. Main risks of bias were underpowered studies, poor recruitment processes, not accounting for other concurrent interventions and short follow up periods. Further research is needed to understand how to address the negative effects of deprescribing interventions.

Trial registration
The protocol was registered with PROSPERO (registration number CRD42019158079)
The association between a priori dietary patterns and psychological disorders in military personnel
Authors: Parastouei Karim , Rostami Hosein , Chambari Mahla 
Published: March 2023

Abstract
Background
Studies have identified a high prevalence of poor mental health, including depression, anxiety, and stress in military occupations. A low quality diet is one of the potential factors related to mental disorders. This study aimed to investigate the association of a priori dietary patterns, including dietary approach to stop hypertension (DASH), the Mediterranean diet (MD), dietary inflammatory index (DII), and healthy eating index-2015 (HEI-2015) with the odds of depression, anxiety, and stress in military staff.

Methods
This cross-sectional study was performed on a total of 400 military staff, aged 38.67 ± 5.22 (ranging from 30 to 60) years, recruited from Iranian military centers. The dietary intake of participants and adherence to the DASH, MD, DII, and HEI-2015 was measured using a 168-item food frequency questionnaire (FFQ). Mental health was evaluated with the use of the Depression, Anxiety, and Stress Scale − 21 (DASS-21).

Results
The prevalence of depression, anxiety, and stress was 64.5%, 63.2%, and 61.3%, respectively. Individuals with the highest adherence to HEI-2015, compared to those with the lowest adherence, were significantly at lower odds of anxiety (OR = 0.51, 95%CI: 0.27–0.96, p = 0.03), while higher adherence to DII was related to a 2.74-fold increased odds of anxiety (OR = 2.74, 95%CI: 1.06–7.04, p = 0.03). Compared to those with the lowest adherence (quartile 1), quartile 2 of the HEI-2015 was associated with decreased odds of stress (p = 0.04). No association was identified between dietary patterns and depression.

Conclusion
Greater adherence to HEI-2015 and lower adherence to DII are associated with lower odds of anxiety in military staff.
Association between impairment and self-rated health: a brazilian population study considering type, origin, and degree of limitation
Authors: Anderle Paula , Ziegelmann Patrícia Klarmann , de Goulart Bárbara Niegia Garcia 
Published: March 2023

Abstract
Background
Perceived health is a well-known, low-cost measure in public health, and has been used in several studies on individuals with impairment. Although many studies have related impairment to self-rated health (SRH), few have considered the origin and degree of limitation of the impairment. This study examined whether physical, hearing, or visual impairments—when analyzed according to origin (congenital or acquired) and degree of limitation (with or without)—are associated with the SRH status.

Methods
This cross-sectional study used data of 43,681 adult individuals from the Brazilian National Health Survey (NHS, 2013). The outcome SRH was dichotomized into poor (including the regular, poor, and very poor responses) or good (including the good and very good responses). Crude and adjusted (for socio-demographic characteristics and chronic diseases history) prevalence ratios (PR) estimates were evaluated using Poisson regression models with the robust variance estimator.

Results
Poor SRH prevalence was estimated at 31.8% (95%CI:31.0–33.0) among the non-impaired population, 65.6% (95%CI:60.6–70.0) among individuals with physical impairment, 50.3% (95%CI:45.0–56.0) for people with hearing impairment, and 55.3% (95%CI:51.8–59.0) for the visually impaired. Individuals with congenital physical impairment—with or without limitations—presented the strongest association with the poorest SRH status. Participants with non-limiting, congenital hearing impairment showed a protective factor to poor SRH (PR = 0.40 95%CI: 0.38–0.52). Individuals with acquired visual impairment with limitations demonstrated the strongest association with poor SRH (PR = 1.48 95%CI:1.47–1.49). Among the impaired population, middle-aged participants showed a stronger association with poor SRH than older adult participants.

Conclusions
Impairment is associated with poor SRH status, especially among people with physical impairment. The origin and degree of limitation of each type of impairment differently impacts SRH among the impaired population.
Staged replacement of both hips and both knees in patients with rheumatoid arthritis
Authors: Cao Jian , Wang Wenqi , Feng Wei , Xu Hong , Wang Duan , Zhou Zongke 
Published: March 2023

Abstract
Background
Patients with rheumatoid arthritis (RA) undergoing bilateral total hip arthroplasty (THA) and total knee arthroplasty (TKA) are an uncommon population, and their outcomes are also difficult to predict. The purpose of this study was to evaluate whether both bilateral cementless THA and cemented posterior-stabilized TKA (PS-TKA) can provide reliable outcomes for RA patients.

Methods
We retrospectively reviewed 30 RA patients (60 hips and 60 knees) who underwent both elective bilateral cementless THA and cemented PS-TKA, with a minimum follow-up of 2 years. Clinical, patient-reported, and radiographic data were retrospectively analyzed.

Results
The mean follow-up was 84 months (range, 24–156). By the last follow-up, the post-operative range of motion, Harris Hip Score, Knee Society Score (KSS) clinical, KSS functional, Western Ontario and McMaster Universities Index of Osteoarthritis (WOMAC) hip, and WOMAC knee scores were significantly improved compared to the preoperative values. All patients achieved the ability to walk. In addition, overall satisfaction scores on a 100-point scale were 92.5 after THA and 89.6 after TKA. Only one patient underwent revision surgery due to knee joint instability, and all replaced hips and knees were radiographically stable by the assessment of the radiolucent line. The proportion of implants that did not suffer loosening or require revision surgery was 99.2% during the 84-month follow-up, based on Kaplan-Meier analysis.

Conclusions
Our study suggests that bilateral cementless THA and cemented PS-TKA provides reliable mid-long-term clinical, patient-reported, and radiographic outcomes in RA patients, with high survivorship and patient satisfaction.
Nurses’ knowledge, attitudes, and practice with regards to nutritional management of diabetes mellitus
Authors: Farzaei Mahsa , Shahbazi Shahla , Gilani Neda , Ostadrahimi Alireza , Gholizadeh Leila 
Published: March 2023

Abstract
Background
The prevalence of diabetes is increasing rapidly worldwide. Nurses work collaboratively with multidisciplinary teams to improve diabetes management. Yet, little is known about nurses’ role in nutritional management of diabetes. This study aimed to evaluate nurses’ knowledge, attitudes, and practice (KAP) toward nutritional management of diabetes.

Methods
This cross-sectional study was conducted with 160 nurses, who were recruited between July 4 and July 18, 2021 from two referral tertiary teaching hospitals in Iran. A validated paper-based self-reported questionnaire was used to assess nurses’ KAP. Data were analyzed using descriptive statistics and multiple linear regression analysis.

Results
The mean knowledge score of nurses about nutritional management of diabetes was 12.16 ± 2.83, and 61.2% showing a moderate knowledge level on nutritional management of diabetes. The mean attitudes score was 60.68 ± 6.11, with 86.92% of participants demonstrating positive attitudes. The mean practice score of study participants was 44.74 ± 7.81, with 51.9% having a moderate level of practice. Higher knowledge scores were observed among male nurses (B = -7.55, p = 0.009) and those with blended learning as a preferred learning method (B = 7.28, p = 0.029). Having an opportunity to provide education to patients with diabetes during shifts affected nurses’ attitudes positively (B = -7.59, p = 0.017). Practice scores were higher among nurses who perceived themselves competent in the nutritional management of diabetes (B = -18.05, p = 0.008).

Conclusion
Nurses’ knowledge and practice in the nutritional management of diabetes should be increased to help improve the quality of the dietary care and patient education they provide these patients. Further studies are needed to confirm the results of this study both in Iran and internationally.
Healthcare provider perceptions on the implementation of the universal test-and-treat policy in South Africa: a qualitative inquiry
Authors: Nicol Edward , Mehlomakulu Vuyelwa , Jama Ngcwalisa Amanda , Hlongwa Mbuzeleni , Basera Wisdom , Pass Desiree , Bradshaw Debbie 
Published: March 2023

Abstract
Background
South Africa had an estimated 7.5 million people living with HIV (PLHIV), accounting for approximately 20% of the 38.4 million PLHIV globally in 2021. In 2015, the World Health Organization recommended the universal test and treat (UTT) intervention which was implemented in South Africa in September 2016. Evidence shows that UTT implementation faces challenges in terms of human resources capacity or infrastructure. We aim to explore healthcare providers (HCPs)’ perspectives on the implementation of the UTT strategy in uThukela District Municipality in KwaZulu-Natal province.

Methods
A qualitative study was conducted with one hundred and sixty-one (161) healthcare providers (HCPs) within 18 healthcare facilities in three subdistricts, comprising of Managers, Nurses, and Lay workers. HCPs were interviewed using an open ended-survey questions to explore their perceptions providing HIV care under the UTT strategy. All interviews were thematically analysed using both inductive and deductive approaches.

Results
Of the 161 participants (142 female and 19 male), 158 (98%) worked at the facility level, of which 82 (51%) were nurses, and 20 (12.5%) were managers (facility managers and PHC manager/supervisors). Despite a general acceptance of the UTT policy implementation, HCPs expressed challenges such as increased patient defaulter rates, increased work overload, caused by the increased number of service users, and physiological and psychological impacts. The surge in the workload under conditions of inadequate systems’ capacity and human resources, gave rise to a greater burden on HCPs in this study. However, increased life expectancy, good quality of life, and immediate treatment initiation were identified as perceived positive outcomes of UTT on service users. Perceived influence of UTT on the health system included, increased number of patients initiated, decreased burden on the system, meeting the 90-90-90 targets, and financial aspects.

Conclusion
Health system strengthening such as providing more systems’ capacity for expected increase in workload, proper training and retraining of HCPs with new policies in the management of patient readiness for lifelong ART journey, and ensuring availability of medicines, may reduce strain on HCPs, thus improving the delivery of the comprehensive UTT services to PLHIV.
Engineering Escherichia coli for efficient assembly of heme proteins
Authors: Ge Jianzhong , Wang Xiaolu , Bai Yingguo , Wang Yaru , Wang Yuan , Tu Tao , Qin Xing , Su Xiaoyun , Luo Huiying , Yao Bin , Huang Huoqing , Zhang Jie 
Published: March 2023

Abstract
Background
Heme proteins, such as hemoglobin, horseradish peroxidase and cytochrome P450 (CYP) enzyme, are highly versatile and have widespread applications in the fields of food, healthcare, medical and biological analysis. As a cofactor, heme availability plays a pivotal role in proper folding and function of heme proteins. However, the functional production of heme proteins is usually challenging mainly due to the insufficient supply of intracellular heme.

Results
Here, a versatile high-heme-producing Escherichia coli chassis was constructed for the efficient production of various high-value heme proteins. Initially, a heme-producing Komagataella phaffii strain was developed by reinforcing the C4 pathway-based heme synthetic route. Nevertheless, the analytical results revealed that most of the red compounds generated by the engineered K. phaffii strain were intermediates of heme synthesis which were unable to activate heme proteins. Subsequently, E. coli strain was selected as the host to develop heme-producing chassis. To fine-tune the C5 pathway-based heme synthetic route in E. coli, fifty-two recombinant strains harboring different combinations of heme synthesis genes were constructed. A high-heme-producing mutant Ec-M13 was obtained with negligible accumulation of intermediates. Then, the functional expression of three types of heme proteins including one dye-decolorizing peroxidase (Dyp), six oxygen-transport proteins (hemoglobin, myoglobin and leghemoglobin) and three CYP153A subfamily CYP enzymes was evaluated in Ec-M13. As expected, the assembly efficiencies of heme-bound Dyp and oxygen-transport proteins expressed in Ec-M13 were increased by 42.3–107.0% compared to those expressed in wild-type strain. The activities of Dyp and CYP enzymes were also significantly improved when expressed in Ec-M13. Finally, the whole-cell biocatalysts harboring three CYP enzymes were employed for nonanedioic acid production. High supply of intracellular heme could enhance the nonanedioic acid production by 1.8- to 6.5-fold.

Conclusion
High intracellular heme production was achieved in engineered E. coli without significant accumulation of heme synthesis intermediates. Functional expression of Dyp, hemoglobin, myoglobin, leghemoglobin and CYP enzymes was confirmed. Enhanced assembly efficiencies and activities of these heme proteins were observed. This work provides valuable guidance for constructing high-heme-producing cell factories. The developed mutant Ec-M13 could be employed as a versatile platform for the functional production of difficult-to-express heme proteins.
Hyperglycemia induces PFKFB3 overexpression and promotes malignant phenotype of breast cancer through RAS/MAPK activation
Authors: Cheng Xiao , Jia Xiupeng , Wang Chunnian , Zhou Shangyan , Chen Jiayi , Chen Lei , Chen Jinping 
Published: March 2023

Abstract
Background
Breast cancer is the most common tumor in women worldwide. Diabetes mellitus is a global chronic metabolic disease with increasing incidence. Diabetes mellitus has been reported to positively regulate the development of many tumors. However, the specific mechanism of hyperglycemic environment regulating breast cancer remains unclear. PFKFB3 (6-phosphofructose-2-kinase/fructose-2, 6-bisphosphatase 3) is a key regulatory factor of the glycolysis process in diabetes mellitus, as well as a promoter of breast cancer. So, we want to explore the potential link between PFKFB3 and the poor prognosis of breast cancer patients with hyperglycemia in this study.

Methods
Cell culture was utilized to construct different-glucose breast cancer cell lines. Immunohistochemistry was adopted to analyze the protein level of PFKFB3 in benign breast tissues, invasive ductal carcinoma with diabetes and invasive ductal carcinoma without diabetes. The Kaplan–Meier plotter database and GEO database (GSE61304) was adopted to analyze the survival of breast cancer patients with different PFKFB3 expression. Western blot was adopted to analyze the protein level of PFKFB3, epithelial–mesenchymal transition (EMT)-related protein and extracellular regulated protein kinases (ERK) in breast cancer cells. Gene Set Cancer Analysis (GSCA) was utilized to investigate the potential downstream signaling pathways of PFKFB3. TargetScan and OncomiR were utilized to explore the potential mechanism of PFKFB3 overexpression by hyperglycemia. Transfections (including siRNAs and miRNA transfection premiers) was utilized to restrain or mimic the expression of the corresponding RNA. Cell functional assays (including cell counting, MTT, colony formation, wound-healing, and cell migration assays) were utilized to explore the proliferation and migration of breast cancer cells.

Results
In this study, we demonstrated that the expression of PFKFB3 in breast cancer complicated with hyperglycemia was higher than that in breast cancer with euglycemia through cell experiment in vitro and histological experiment. PFKFB3 overexpression decreased the survival period of breast cancer patients and was correlated with a number of clinicopathological parameters of breast cancer complicated with diabetes. PFKFB3 promoted the proliferation and migration of breast cancer in a hyperglycemic environment and might be regulated by miR-26. In addition, PFKFB3 stimulated epithelial-mesenchymal transition of breast cancer in a hyperglycemic environment. In terms of downstream mechanism exploration, we predicted and verified the cancer-promoting effect of PFKFB3 in breast cancer complicated with hyperglycemia through RAS/MAPK pathway.

Conclusions
In conclusion, PFKFB3 could be overexpressed by hyperglycemia and might be a potential therapeutic target for breast cancer complicated with diabetes.
The CLDN5 gene at the blood-brain barrier in health and disease
Authors: Hashimoto Yosuke , Greene Chris , Munnich Arnold , Campbell Matthew 
Published: March 2023

AbstractThe CLDN5 gene encodes claudin-5 (CLDN-5) that is expressed in endothelial cells and forms tight junctions which limit the passive diffusions of ions and solutes. The blood–brain barrier (BBB), composed of brain microvascular endothelial cells and associated pericytes and end-feet of astrocytes, is a physical and biological barrier to maintain the brain microenvironment. The expression of CLDN-5 is tightly regulated in the BBB by other junctional proteins in endothelial cells and by supports from pericytes and astrocytes. The most recent literature clearly shows a compromised BBB with a decline in CLDN-5 expression increasing the risks of developing neuropsychiatric disorders, epilepsy, brain calcification and dementia. The purpose of this review is to summarize the known diseases associated with CLDN-5 expression and function. In the first part of this review, we highlight the recent understanding of how other junctional proteins as well as pericytes and astrocytes maintain CLDN-5 expression in brain endothelial cells. We detail some drugs that can enhance these supports and are being developed or currently in use to treat diseases associated with CLDN-5 decline. We then summarise mutagenesis-based studies which have facilitated a better understanding of the physiological role of the CLDN-5 protein at the BBB and have demonstrated the functional consequences of a recently identified pathogenic CLDN-5 missense mutation from patients with alternating hemiplegia of childhood. This mutation is the first gain-of-function mutation identified in the CLDN gene family with all others representing loss-of-function mutations resulting in mis-localization of CLDN protein and/or attenuated barrier function. Finally, we summarize recent reports about the dosage-dependent effect of CLDN-5 expression on the development of neurological diseases in mice and discuss what cellular supports for CLDN-5 regulation are compromised in the BBB in human diseases.