bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cacna2d2 inhibits axonal regeneration following surgical decompression in a rat model of cervical spondylotic myelopathy
Authors: Liu Peisheng , Li Xiaofeng , Liu Jing , Zhang Hengjia , You Zhitao , Zhang Jianfeng 
Published: July 2022

Abstract
Background
Cervical spondylotic myelopathy (CSM) is a clinically symptomatic condition due to spinal cord compression, leading to spinal cord dysfunction. Surgical decompression is the main treatment of CSM, but the mechanisms of axonal regeneration after surgical decompression are still fragmentary.

Methods
In a rat model of CSM, the cacna2d2 (α2δ2) expression levels in anterior horn of spinal cord were observed following compression and decompression by western blot and immunofluorescence. The expression levels of 5 hydroxytryptamine (5HT) and GAP43 were also analyzed by immunofluorescence. Furthermore, gabapentin intervention was performed for 4 weeks after decompression to analyze the changes of behaviors and anterior horn of spinal cords.

Results
Following decompression, the expression levels of α2δ2 in the anterior horn of spinal cord were decreased, but the expression levels of 5HT andGAP43 were increased. Compared with the vehicle treated rats, gabapentin treatment for 4 weeks ameliorated the behaviors of rats and improved the damaged anterior horn of spinal cord. Besides, inhibition of α2δ2 through gabapentin intervention enhanced the axonal regeneration in the anterior horn of damaged spinal cord.

Conclusions
Inhibition of α2δ2 could enhance axonal recovery in anterior horn of damaged spinal cord induced by CSM after surgical decompression, providing a potential method for promoting axon regeneration following surgery.
Preoperative frailty and chronic pain after cardiac surgery: a prospective observational study
Authors: Arends Britta C. , Timmerman Leon , Vernooij Lisette M. , Verwijmeren Lisa , Biesma Douwe H. , van Dongen Eric P. A. , Noordzij Peter G. , van Oud-Alblas Heleen J Blussé 
Published: July 2022

Abstract
Background
Chronic pain after cardiac surgery, whether or not related to the operation, is common and has negative impact on health related quality of life (HRQL). Frailty is a risk factor for adverse surgical outcomes, but its relationship with chronic pain after cardiac surgery is unknown. This study aimed to address the association between frailty and chronic pain following cardiac surgery.

Methods
This sub-study of the Anesthesia Geriatric Evaluation study included 518 patients ≥ 70 years undergoing elective cardiac surgery. Pain was evaluated with the Short-Form 36 questionnaire prior to and one year after surgery. Associations between chronic postoperative pain and frailty domains, including medication use, nutritional status, mobility, physical functioning, cognition, HRQL, living situation and educational level, were investigated with multivariable regression analysis.

Results
Chronic pain one year after cardiac surgery was reported in 182 patients (35%). Medication use, living situation, mobility, gait speed, Nagi’s physical functioning and preoperative HRQL were frailty domains associated with chronic pain after surgery. For patients with chronic pain physical HRQL after one year was worse compared to patients without chronic pain (β –10.37, 99% CI –12.57 – –8.17).

Conclusions
Preoperative polypharmacy, living alone, physical frailty and lower mental HRQL are associated with chronic pain following cardiac surgery. Chronic postoperative pain is related to worse physical HRQL one year after cardiac surgery. These findings may guide future preoperative interventions to reduce chronic pain and poor HRQL after cardiac surgery in older patients.

Trial Registration
This trial has been registered before initiation under number NCT02535728 at clinicaltrials.gov.
Correlation between crown-rump length in the first trimester of pregnancy and neonatal outcomes
Authors: Xu Yin , Ni Meng , Zhang Qianqian , Zhao Jiuru , Tang Zheng , Liu Zhiwei 
Published: July 2022

Abstract
Background
To investigate the association of crown-rump length (CRL) during the first trimester of pregnancy with neonatal outcomes.

Methods
A total of 15,524 women with a reliable first day of the last menstrual period and a regular menstrual cycle (28 ± 4 days) were included from January 2015 to November 2016. CRL was measured by ultrasound from 7+0 to 13+6 weeks during pregnancy and transformed to a standard deviation score (SDS) adjusted for gestational age. Linear regression was used to explore risk factors for CRL. A generalised linear model was used to evaluate the association between CRL and neonatal outcomes.

Results
In the multivariate analysis, maternal age (0.25 mm, 95% CI = [0.22–0.28], P < 0.001; 0.04 SDS, 95% CI = [0.03–0.04], P < 0.001), multipara (0.30 mm, 95% CI = [0.08–0.52], P = 0.007; 0.04 SDS, 95% CI = [0.00–0.07], P = 0.031) and folic acid supplement use (0.78 mm, 95% CI = [0.49–1.08], P < 0.001; 0.05 SDS, 95% CI = [0.01–0.10], P < 0.019) were positively associated with CRL, while pre-pregnancy BMI (-0.17 mm, 95% CI = [-0.21 to -0.13], P < 0.001; -0.02 SDS, 95% CI = [-0.03 to -0.02], P < 0.001) was negatively related to CRL. For neonatal outcomes, CRL was negatively associated with small for gestational age (SGA) ([risk ratio] (RR) = 0.733, 95% [CI] = 0.673–0.8004, Padjusted < 0.001) and neonatal intensive care unit (NICU) admission ([RR] = 0.928, 95% [CI] = 0.883–0.976, Padjusted = 0.003), and preterm birth ([RR] = 1.082, 95% [CI] = 1.008–1.162, Padjusted = 0.029), but positively related to large for gestational age (LGA) ([RR] = 1.241, 95% [CI] = 1.184–1.301, Padjusted = 0.012). When stratified by pre-pregnancy BMI, the risk of SGA and LGA remained significant in all groups, while the increased risk of preterm birth was only observed in the lean group (BMI < 18.5 kg/m2) and decreased risk of NICU admission rate in the normal group (BMI 18.5–24 kg/m2).

Conclusions
Maternal characteristics were independently associated with CRL in the first trimester, which was negatively related to foetal size, SGA, preterm birth, and admission rate to the NICU, but positively related to LGA.
Developing shelf-stable Microbiota Directed Complementary Food (MDCF) prototypes for malnourished children: study protocol for a randomized, single-blinded, clinical study
Authors: Mostafa Ishita , Fahim Shah Mohammad , Das Subhasish , Gazi Md Amran , Hasan Md. Mehedi , Saqeeb Kazi Nazmus , Mahfuz Mustafa , Lynn Hannah B. , Barratt Michael J. , Gordon Jeffrey I. , Ahmed Tahmeed 
Published: July 2022

Abstract
Background
Childhood undernutrition is a major public health concern that needs special attention to achieve 2025 global nutrition targets. Moderate acute malnutrition (MAM), manifest as wasting (low weight-for-height), affects 33 million children under 5, yet there are currently no global guidelines for its treatment. We recently performed a randomized-controlled clinical study of a microbiota-directed complementary food formulation (MDCF-2) in 12-18-month-old Bangladeshi children with MAM. The results revealed that MDCF-2, freshly prepared each day, produced a significantly greater improvement in ponderal growth than a standard ready-to-use supplementary food (RUSF), an effect that is associated with repair of the disrupted gut microbial community development that occurs in children with MAM. To test the generalizability of these results in acutely malnourished children at other sites, there is a pressing need for a packaged, shelf-stable, organoleptically-acceptable formulation that is bioequivalent to MDCF-2. This report describes the protocol for a clinical study to evaluate candidate formulations designed to meet these criteria.

Methods
A randomized single-blind study will be conducted in 8-12-month-old Bangladeshi children with MAM to compare the efficacy of alternative shelf-stable MDCF prototypes versus the current MDCF-2 formulation that is produced fresh each day. V4-16S rDNA amplicon and shotgun sequencing datasets will be generated from faecal DNA samples collected from each child enrolled in each group prior to, during, and after treatment to determine the abundances of MDCF-2-responsive bacterial taxa. Efficacy will be assessed by quantifying the change in representation of MDCF-2-responsive gut bacterial taxa after 4-weeks of treatment with freshly prepared MDCF-2 compared to their changes in abundance after treatment with the prototype MDCFs. Equivalence will be defined as the absence of a statistically significant difference, after 4-weeks of treatment, in the representation of faecal bacterial taxa associated with the response to MDCF-2 in participants receiving a test MDCF.

Discussion
This trial aims to establish acceptability and equivalence with respect to microbiota repair, of scalable, shelf-stable formulations of MDCF-2 in 8-12-month-old Bangladeshi children with moderate acute malnutrition.

Trial registration
ClinicalTrials.gov (NCT05094024). The trial has been registered before starting enrolment on 23 October 2021.
Alterations in circulating levels of vitamin D binding protein, total and bioavailability of vitamin D in diabetic retinopathy patients
Authors: Maghbooli Zhila , Ebrahimi Meimand Sepideh , Malek Hosseini Ali-Asghar , Shirvani Arash 
Published: July 2022

Abstract
Aims
This study aimed to investigate the association between circulating levels of vitamin D binding protein (VDBP) and its genotypes and diabetic retinopathy risk.

Methods
This case–control study recruited 154 patients with type 2 diabetes mellitus; 62 with diabetic retinopathy (DR) and 92 without DR and diabetic nephropathy (DN). Circulating levels of 25-hydroxyvitamin D3 and VDBP levels were measured in the patients. The genotype and phenotype of VDBP were evaluated based on two common VDBP variations; rs7041 and rs4588.

Results
Serum levels of VDBP were significantly lower in patients with DR than in patients without DR and/or DN (Ln-VDBP (μg/ml): 6.14 ± 0.92 vs. 6.73 ± 1.45, p = 0.001) even after adjustment for age, sex, body mass index, disease duration, estimated glomerular filtration rate (eGFR), HbA1C, insulin therapy profile, and serum levels of 25(OH)D. The distribution of VDBP phenotypes and genotypes in the two studied groups were nearly the same, and the distribution was similar to that of the general population.

Conclusions
In this study, we found the association between lower circulating levels of VDBP and risk of DR. However, the precise mechanism linking these two remains unknown. Further and more in-depth research is needed to find out the underlying causes of the relationship.
Luteolin alleviates inflammation and autophagy of hippocampus induced by cerebral ischemia/reperfusion by activating PPAR gamma in rats
Authors: Li Lu , Pan Guanghua , Fan Rong , Li Dalei , Guo Lei , Ma Lili , Liang Hui , Qiu Jiaoxue 
Published: July 2022

Abstract
Background
Luteolin, a flavonoid compound with anti-inflammatory activity, has been reported to alleviate cerebral ischemia/reperfusion (I/R) injury. However, its potential mechanism remains unclear.

Methods
The binding activity of luteolin to peroxisome proliferator-activated receptor gamma (PPARγ) was calculated via molecular docking analysis. Rats were subjected to middle cerebral artery occlusion and reperfusion (MCAO/R). After reperfusion, vehicle, 25 mg/kg/d luteolin, 50 mg/kg/d luteolin, 10 mg/kg/d pioglitazone, 50 mg/kg/d luteolin combined with 10 mg/kg/d T0070907 (PPARγ inhibitor) were immediately orally treatment for 7 days. ELISA, TTC staining, H&E staining, immunohistochemistry, immunofluorescence and transmission electron microscope methods were performed to evaluate the inflammation and autophagy in damaged hippocampal region. The PPARγ, light chain 3 (LC3) B-II/LC3B-I and p-nuclear factor-κB (NF-κB) p65 proteins expression levels in damaged hippocampal region were analyzed.

Results
Luteolin showed good PPARγ activity according to docking score (score = − 8.2). Luteolin treatment downregulated the infarct area and the pro-inflammatory cytokines levels caused by MCAO/R injury. Moreover, luteolin administration ameliorated neuroinflammation and autophagy in damaged hippocampal region. Pioglitazone plays protective roles similar to luteolin. T0070907 concealed the neuroprotective roles of 50 mg/kg/d luteolin.

Conclusions
Luteolin exerts neuroprotective roles against inflammation and autophagy of hippocampus induced by cerebral I/R by activating PPARγ in rats.
Using an optimized generative model to infer the progression of complications in type 2 diabetes patients
Authors: Wang Xiaoxia , Lin Yifei , Xiong Yun , Zhang Suhua , He Yanming , He Yuqing , Zhang Zhikun , Plasek Joseph M. , Zhou Li , Bates David W. , Tang Chunlei 
Published: July 2022

Abstract
Background
People live a long time in pre-diabetes/early diabetes without a formal diagnosis or management. Heterogeneity of progression coupled with deficiencies in electronic health records related to incomplete data, discrete events, and irregular event intervals make identification of pre-diabetes and critical points of diabetes progression challenging.

Methods
We utilized longitudinal electronic health records of 9298 patients with type 2 diabetes or prediabetes from 2005 to 2016 from a large regional healthcare delivery network in China. We optimized a generative Markov-Bayesian-based model to generate 5000 synthetic illness trajectories. The synthetic data were manually reviewed by endocrinologists.

Results
We build an optimized generative progression model for type 2 diabetes using anchor information to reduce the number of parameters learning in the third layer of the model from $$O\left(N\times W\right)$$

O

N
×
W

to $$O\left((N-C)\times W\right)$$

O

(
N
-
C
)
×
W

, where $$N$$
N
is the number of clinical findings, $$W$$
W
is the number of complications, $$C$$
C
is the number of anchors. Based on this model, we infer the relationships between progression stages, the onset of complication categories, and the associated diagnoses during the whole progression of type 2 diabetes using electronic health records.

Discussion
Our findings indicate that 55.3% of single complications and 31.8% of complication patterns could be predicted early and managed appropriately to potentially delay (as it is a progressive disease) or prevented (by lifestyle modifications that keep patient from developing/triggering diabetes in the first place).

Conclusions
The full type 2 diabetes patient trajectories generated by the chronic disease progression model can counter a lack of real-world evidence of desired longitudinal timeframe while facilitating population health management.
Development and validation of a health information system for assistance and research in gestational trophoblast disease
Authors: Martins Jaqueline , Bandiera-Paiva Paulo , Neto Antonio Rodrigues Braga , de Carvalho Lucas Ribeiro Borges , Padrini-Andrade Lúcio , Machado Vitor Tonini , da Silva Junior Antônio Carlos , Sun Sue Yazaki 
Published: July 2022

Abstract
Background
Gestational Trophoblastic Disease (GTD) comprises pathological forms of placental trophoblastic tissue proliferation. When benign, they present with hydatidiform moles, and when malignant, they are called Gestational Trophoblastic Neoplasia. With the growth of the practice of digital health, allied to updated therapeutic approaches, the Outpatient Clinic for Gestational Trophoblastic Disease has built a Health Information System (HIS), contributing to the teaching–learning binomial, as well as to self-care.

Methods
This is a cross-sectional and blind technological assessment research for developing SIS-Mola (Website for the medical team and the Application “MolaApp” aimed at patients with GTD). We used the Praxis management approach to manage the application creation project. In the tasks involving real-time chat, a WebSocket layer was created and hosted together with the project’s web services, which use the Arch Linux operating system. For the evaluations, we provided questionnaires developed based on the System Usability Scale (SUS), to determine the degree of user satisfaction, with objective questions on the Likert scale. We invited 28 participants for the evaluations, among ABDTG specialist physicians, doctors from the DTG Outpatient Clinic team, and the patients. The study was systematized according to the rules of treatment and follow-up in treating the disease.

Results
The tests were conducted from November 2021 to February 2022. The responses obtained on a Likert scale indicated reliability and credibility to the HIS, since the total usability score, measured by the ten questions of the SUS instrument, had a mean of 81.1 (clinicians), 80 (patients) and median of 77.5 for both groups. The sample was characterized according to the variables: age, gender, education, computer knowledge, and profession.

Conclusion
Developing a HIS in the GTD Outpatient Clinic met the objectives regarding the rules of treatment and follow-up of patients. With these digital tools, it is possible to obtain data about the patient’s health, sending information through exams performed and appropriate treatments. The connectivity capacity allows agile care, saving time, costs and solving the displacement problem. The TICs generate natural efficiency for the organization in the flow of service and the formation of a database, improving the quality of the assistance.
Provider competence in hypertension management and challenges of the rural primary healthcare system in Sichuan province, China: a study based on standardized clinical vignettes
Authors: Wu Yuju , Ye Ruixue , Wang Qingzhi , Sun Chang , Meng Sha , Sylvia Sean , Zhou Huan , Friesen Dimitris , Rozelle Scott 
Published: July 2022

Abstract
Background
Improving primary care providers’ competence is key to detecting and managing hypertension, but evidence to guide this work has been limited, particularly for rural areas. This study aimed to use standardized clinical vignettes to assess the competence of providers and the ability of the primary healthcare system to detect and manage hypertension in rural China.

Methods
A multi-stage random sampling method was administered to select target health facilities, providers, and households. The clinical vignette script was developed to evaluate provider competence in managing first-visit patients with symptoms of hypertension. Logistic regression was used to explore the factors correlated with provider competence. Provider referral and management rates were combined with patients’ facility sorting behaviors to assess the ability of the rural healthcare system to manage hypertension in three policy scenarios.

Results
A total of 306 providers and 153 facilities were enrolled in our study. In the 306 clinical vignette interactions, 25.9% of providers followed the national guidelines for hypertension consultation. The correct diagnosis was achieved by only 10.1% of providers, and 30.4% of providers were able to prescribe the correct treatment. Multi-variable regression results showed that younger providers (OR = 0.85, 95%CI: 0.73, 0.98) and those who work in township health centers (OR = 4.47, 95%: 1.07, 18.67) were more likely to provide a correct diagnosis. In a free-selection scenario, 29.8% of patients with hypertension were managed correctly throughout the rural system. When all patients first visit village clinics, system-level correct management is reduced to 20.5% but increases to 45.0% when all patients first visit township health centers.

Conclusions
Rural primary care providers do not have enough competence to detect and treat hypertension cases in China to an acceptable degree. Policy constraints may limit the competence of the rural healthcare system. Research to improve detection and treatment competence in hypertension and optimize health policy is needed.
Challenges to implementing artificial intelligence in healthcare: a qualitative interview study with healthcare leaders in Sweden
Authors: Petersson Lena , Larsson Ingrid , Nygren Jens M. , Nilsen Per , Neher Margit , Reed Julie E. , Tyskbo Daniel , Svedberg Petra 
Published: July 2022

Abstract
Background
Artificial intelligence (AI) for healthcare presents potential solutions to some of the challenges faced by health systems around the world. However, it is well established in implementation and innovation research that novel technologies are often resisted by healthcare leaders, which contributes to their slow and variable uptake. Although research on various stakeholders’ perspectives on AI implementation has been undertaken, very few studies have investigated leaders’ perspectives on the issue of AI implementation in healthcare. It is essential to understand the perspectives of healthcare leaders, because they have a key role in the implementation process of new technologies in healthcare. The aim of this study was to explore challenges perceived by leaders in a regional Swedish healthcare setting concerning the implementation of AI in healthcare.

Methods
The study takes an explorative qualitative approach. Individual, semi-structured interviews were conducted from October 2020 to May 2021 with 26 healthcare leaders. The analysis was performed using qualitative content analysis, with an inductive approach.

Results
The analysis yielded three categories, representing three types of challenge perceived to be linked with the implementation of AI in healthcare: 1) Conditions external to the healthcare system; 2) Capacity for strategic change management; 3) Transformation of healthcare professions and healthcare practice.

Conclusions
In conclusion, healthcare leaders highlighted several implementation challenges in relation to AI within and beyond the healthcare system in general and their organisations in particular. The challenges comprised conditions external to the healthcare system, internal capacity for strategic change management, along with transformation of healthcare professions and healthcare practice. The results point to the need to develop implementation strategies across healthcare organisations to address challenges to AI-specific capacity building. Laws and policies are needed to regulate the design and execution of effective AI implementation strategies. There is a need to invest time and resources in implementation processes, with collaboration across healthcare, county councils, and industry partnerships.