bluuebunny/crossref_metadata_2025_split huggingface dataset:
MINocyclinE to Reduce inflammation and blood brain barrier leakage in small Vessel diseAse (MINERVA) trial study protocol
Authors: Brown Robin B , Tozer Daniel J , Loubière Laurence , Hong Young T , Fryer Tim D , Williams Guy B , Graves Martin J , Aigbirhio Franklin I , O’Brien John T , Markus Hugh S 
Published: May 2022

Background: Cerebral small vessel disease (SVD) is a common cause of stroke and cognitive impairment. Recent data has implicated neuroinflammation and increased blood-brain barrier (BBB) permeability in its pathogenesis, but whether such processes are causal and can be therapeutically modified is uncertain. In a rodent model of SVD, minocycline was associated with reduced white matter lesions, inflammation and BBB permeability. Aims: To determine whether blood-brain barrier permeability (measured using dynamic contrast-enhanced MRI) and microglial activation (measured by positron emission tomography using the radioligand 11C-PK11195) can be modified in SVD. Design: Phase II randomised double blind, placebo-controlled trial of minocycline 100 mg twice daily for 3 months in 44 participants with moderate to severe SVD defined as a clinical lacunar stroke and confluent white matter hyperintensities. Outcomes: Primary outcome measures are volume and intensity of focal increases of blood-brain barrier permeability and microglial activation determined using PET-MRI imaging. Secondary outcome measures include inflammatory biomarkers in serum, and change in conventional MRI markers and cognitive performance over 1 year follow up. Discussion: The MINERVA trial aims to test whether minocycline can influence novel pathological processes thought to be involved in SVD progression, and will provide insights into whether central nervous system inflammation in SVD can be therapeutically modulated.
Return to Play After Isolated Syndesmotic Ligamentous Injury in Athletes: A Systematic Review and Meta-analysis
Authors: Salameh Motasem , Hantouly Ashraf T. , Rayyan Abdallah , Dabbas Jood , Toubasi Ahmad A. , Hartnett Davis A. , Blankenhorn Brad 
Published: May 2022

Background: Syndesmotic ankle sprains are common and challenging injuries for athletes. The management of such injuries is controversial, with a paucity of evidence on treatment protocols with unpredictability regarding the time lost to participate in sports following injury. The present study seeks to review and report the return to play (RTP) time and examine the outcomes and complications of ankle syndesmotic sprains in the athletic population. Methods: PubMed, Cochrane Library, and Google Scholar were queried in August 2021 for case series, cohorts, and randomized controlled trials that evaluated return to play time after ankle syndesmotic sprains. The primary outcomes were the rate and time to return to play after syndesmotic ankle sprains for both surgical and nonsurgical treatment. Secondary outcomes included short-term complications and recurrence. Results: Eighteen articles were eligible for meta-analysis with a total of 1133 syndesmotic sprains. The overall RTP was 99% (95% CI 0.96, 1.00), the overall mean RTP was 52.32 days (95% CI 39.01, 65.63). Pooled RTP for surgically treated patients was 70.94 days (95% CI 47.04, 94.85), whereas it was 39.33 days (95% CI 28.78, 49.88) for nonsurgically treated cases. A low incidence of recurrence and complications were reported. Conclusion: This article reports a high rate of RTP after syndesmotic sprains. Grade of injury and surgical vs conservative management can affect the time to RTP in high-level athletes. Level of Evidence: Level IV, systematic review and meta-analysis.
Temporomandibular disorder and headache prevalence: A systematic review and meta-analysis
Authors: Yakkaphan Pankaew , Smith Jared G , Chana Pav , Renton Tara , Lambru Giorgio 
Published: May 2022

Background: Temporomandibular disorders (TMD) and headaches are prevalent among the global population. Patients often suffer from both conditions, and they are likely to be associated in a bidirectional way. However, the nature of the association remains unclear. Understanding the epidemiological aspects of the relationship between these conditions could have important clinical implications. Objective: To evaluate the prevalence of headaches in TMD patients as well as the prevalence of TMD in patients who suffer from headaches. Method: A systematic literature search was conducted using electronic databases. Studies published in English and those that used an acknowledged diagnostic criteria for TMD and headaches were included. Study quality was assessed using the Newcastle-Ottawa scale and meta-analyses were performed to generate pooled prevalence estimates. Result: Thirty-one studies met the selection criteria for the review; 16 studies evaluated the prevalence of headache in TMD patients and 15 studies evaluated the prevalence of TMD in headache patients. The included studies were of moderate-to-high quality. Meta-analyses revealed moderate-to-large heterogeneities across included studies. Pooled prevalence estimates from meta-analyses indicated similar rates of headaches in TMD patients and of TMD in headache patients (61.58%, 95% CI 45.26–76.66 and 59.42%, 95% CI 51.93–66.60, respectively). Migraines were more commonly observed in TMD patients (40.25%, 95% CI 35.37–45.23) compared to tension-type headaches (18.89%, 95% CI 12.36–26.44). The prevalence of headaches was particularly high in painful-TMD (82.80%, 95% CI 75.41–89.10). Conclusion: Despite large variance in prevalence rates across included studies, this review suggests headache and TMD frequently co-occur, particularly in the case of migraines and muscle related TMD. This association has important clinical, pathophysiological and therapeutic implications.
Disc–fovea distance and choroidal thickness: is there a relationship?
Authors: Cevher Selim , Barış Üçer Mehmet , Şahin Tayfun 
Published: May 2022

Background: The distance between the optic disc center and the fovea is a biometric parameter; however, it is unclear whether DFD (disc–fovea distance) affects the choroidal thickness. Objective: The aim of this study is to investigate the association between DFD and choroidal thickness. Design: This is a prospective, and cross-sectional study. Methods: Two hundred fifty eyes of 250 healthy participants were examined in terms of DFD, age, axial length, spherical equivalent, and choroidal thickness. Inclusion criteria included aged between 20–40 years, no posterior segment disorders, and participants with best-corrected visual acuity (10/10 according to Snellen’s chart). Participants with high hypermetropia (>4 diopter) or myopia (>6 diopter) or any systemic disease likely to affect choroidal thickness were excluded. Choroidal thickness measurements were performed at subfoveal, 1.0 mm temporal, and 1.0 mm nasal using the enhanced-depth imaging optical coherence tomography. Results: The mean age of all the participants was 26.21 ± 5.73 years, mean DFD was 4634.29 ± 274.70 µm, mean axial length was 23.62 ± 0.83 mm, and mean spherical equivalent was −0.61 ± 1.06 diopter. The mean subfoveal, nasal, and temporal choroidal thicknesses were 388.73 ± 90.15 µm, 351.26 ± 88.09 µm, and 366.50 ± 79.56 µm, respectively. A negative correlation was found between subfoveal, nasal, and temporal choroidal thicknesses and axial length ( r = −0.157, p = 0.013; r = −0.168, p = 0.008; r = −0.174, p = 0.006, respectively). Insignificant correlation was found between choroidal thicknesses and spherical equivalent ( p > 0.05). There was not a statistically significant correlation between DFD and subfoveal, nasal, and temporal choroidal thicknesses ( r = −0.028, p = 0.655; r = 0.030, p = 0.641; r = −0.025, p = 0.699, respectively). In addition, there was not a statistically significant correlation between age and choroidal thickness. Conclusion: This study shows that DFD and spherical equivalent do not affect choroidal thickness; axial length negatively affects choroidal thickness. In addition, age does not affect choroidal thickness between 20 and 40 years.
Transcriptome and metabolome reveal the accumulation of secondary metabolites in different varieties of Cinnamomum longepaniculatum
Authors: Zhao Xin , Yan Yue , Zhou Wan-hai , Feng Rui-zhang , Shuai Yong-kang , Yang Li , Liu Meng-jie , He Xiu-yan , Wei Qin 
Published: May 2022

Abstract
Background
Cinnamomum longepaniculatum (Gamble) N. Chao ex H. W. Li, whose leaves produce essential oils, is a traditional Chinese medicine and economically important tree species. In our study, two C. longepaniculatum varieties that have significantly different essential oil contents and leaf phenotypes were selected as the materials to investigate secondary metabolism.

Result
The essential oil content and leaf phenotypes were different between the two varieties. When the results of both transcriptome and metabolomic analyses were combined, it was found that the differences were related to phenylalanine metabolic pathways, particularly the metabolism of flavonoids and terpenoids. The transcriptome results based on KEGG pathway enrichment analysis showed that pathways involving phenylpropanoids, tryptophan biosynthesis and terpenoids significantly differed between the two varieties; 11 DEGs (2 upregulated and 9 downregulated) were associated with the biosynthesis of other secondary metabolites, and 12 DEGs (2 upregulated and 10 downregulated) were related to the metabolism of terpenoids and polyketides. Through further analysis of the leaves, we detected 196 metabolites in C. longepaniculatum. The abundance of 49 (26 downregulated and 23 upregulated) metabolites differed between the two varieties, which is likely related to the differences in the accumulation of these metabolites. We identified 12 flavonoids, 8 terpenoids and 8 alkaloids and identified 4 kinds of PMFs from the leaves of C. longepaniculatum.

Conclusions
The combined results of transcriptome and metabolomic analyses revealed a strong correlation between metabolite contents and gene expression. We speculate that light leads to differences in the secondary metabolism and phenotypes of leaves of different varieties of C. longepaniculatum. This research provides data for secondary metabolite studies and lays a solid foundation for breeding ideal C. longepaniculatum plants.
How accurate are geriatricians’ fall predictions?
Authors: Wilbur Jason , Jogerst Gerald , Butler Nicholas , Xu Yinghui 
Published: May 2022

Abstract
Background
Older patients are at increased risk of falling and of serious morbidity and mortality resulting from falls. The ability to accurately identify older patients at increased fall risk affords the opportunity to implement interventions to reduce morbidity and mortality. Geriatricians are trained to assess older patients for fall risk. If geriatricians can accurately predict fallers (as opposed to evaluating for individual risk factors for falling), more aggressive and earlier interventions could be employed to reduce falls in older adult fallers. However, there is paucity of knowledge regarding the accuracy of geriatrician fall risk predictions. This study aims to determine the accuracy of geriatricians in predicting falls.

Methods
Between October 2018 and November 2019, a convenience sample of 100 subjects was recruited from an academic geriatric clinic population seeking routine medical care. Subjects performed a series of gait and balance assessments, answered the Stay Independent Brochure and were surveyed about fall incidence 6–12 months after study entry. Five geriatricians, blinded to subjects and fall outcomes, were provided the subjects’ data and asked to categorize each as a faller or non-faller. No requirements were imposed on the geriatricians’ use of the available data. These predictions were compared to predictions of an examining geriatrician who performed the assessments and to fall outcomes reported by subjects.

Results
Kappa values for the 5 geriatricians who used all the available data to classify participants as fallers or non-fallers compared with the examining geriatrician were 0.42 to 0.59, indicating moderate agreement. Compared to screening tools’ mean accuracy of 66.6% (59.6–73.0%), the 5 geriatricians had a mean accuracy for fall prediction of 67.4% (57.3–71.9%).

Conclusions
This study adds to the scant knowledge available in the medical literature regarding the abilities of geriatricians to accurately predict falls in older patients. Studies are needed to characterize how geriatrician assessments of fall risk compare to standardized assessment tools.
Adverse effects following COVID-19 vaccination in Iran
Authors: Babaee Ebrahim , Amirkafi Ali , Tehrani-Banihashemi Arash , SoleimanvandiAzar Neda , Eshrati Babak , Rampisheh Zahra , Asadi-Aliabadi Mehran , Nojomi Marzieh 
Published: May 2022

Abstract
Background
Vaccination is a key intervention to prevent COVID-19. Many vaccines are administered globally, yet there is not much evidence regarding their safety and adverse effects. Iran also faces this challenge, especially as data regarding the Sputnik V vaccine is sparse. Therefore, the aim of this study is to determine the adverse effects of the most commonly used vaccines in Iran.

Methods
Using a retrospective cohort study design, 6600 subjects aged 18 years or older who had received two doses of any of the three COVID-19 vaccines (Sinopharm, AstraZeneca, and Sputnik V) were selected using a random sampling method between March and August 2021. Subjects were asked about any adverse effects of the vaccines by trained interviewers via telephone interview. Vaccine-related adverse effects in individuals during the first 72 h and subsequently following both doses of the vaccines were determined. The demographic variables, type of administered vaccine, adverse effects, and history of the previous infection with COVID-19 were collected. Descriptive statistics (mean, standard deviation) and analytical statistics (Chi-squared and Wilcoxon tests) were performed at a 95% significance level using STATA software version 15 (STATA Corp, College Station, TX, USA).

Results
From 6600 participants, 4775 responded (response rate = 72.3%). Of the participants, 1460 (30.6%) received the AstraZeneca vaccine, 1564 (32.8%) received the Sinopharm vaccine and 1751 (36.7%) received the Sputnik V vaccine. 2653 participants (55.56%) reported adverse effects after the first dose and 1704 (35.7%) after the second dose. Sputnik V caused the most adverse effects with 1449 (82.7%) vaccine recipients reporting symptoms after the first or second dose, compared with 1030 (70.5%) for AstraZeneca and only 585 (37.4%) for the Sinopharm vaccine. The most common adverse effects after the first dose were fatigue (28.37%), chill/fever (26.86%), and skeletal pain (22.38%). These three adverse effects were the same for the second dose, although their prevalence was lower.

Conclusions
In this study, we demonstrate that the Sputnik V vaccine has the highest rate of adverse effects, followed by the AstraZeneca and Sinopharm vaccines. COVID-19 vaccines used in Iran are safe and there were no reports of serious adverse effects.
Severe disease exacerbation after mRNA COVID-19 vaccination unmasks suspected multiple sclerosis as neuromyelitis optica spectrum disorder: a case report
Authors: Lohmann Lisa , Glaser Felix , Möddel Gabriel , Lünemann Jan D. , Wiendl Heinz , Klotz Luisa 
Published: May 2022

Abstract
Background
Since the beginning of the COVID-19 pandemic and development of new vaccines, the issue of post-vaccination exacerbation or manifestation of demyelinating central nervous system (CNS) disorders has gained increasing attention.

Case presentation
We present a case of a 68-year-old woman previously diagnosed with multiple sclerosis (MS) since the 1980s who suffered a rapidly progressive severe sensorimotor paraparesis with loss of bladder and bowel control due to an acute longitudinal extensive transverse myelitis (LETM) after immunization with the mRNA Pfizer–BioNTech COVID-19 vaccine. Detection of Aquaporin-4-antibodies (AQP4) in both serum and CSF led to diagnosis of AQP4-antibody positive neuromyelitis optica spectrum disorder (NMOSD). Treatment with intravenous corticosteroids and plasmapheresis led to a slight improvement of the patient’s symptoms.

Conclusions
Pathogenic mechanisms of post-vaccination occurrence of NMOSD are still unknown. However, cases like this should make aware of rare neurological disorders manifesting after vaccination and potentially contribute to improvement of management of vaccinating patients with inflammatory CNS disorders in the future. So far two cases of AQP4-antibody positive NMOSD have been reported in association with viral vector COVID-19 vaccines. To our knowledge, we report the first case of AQP4-antibody positive NMOSD after immunization with an mRNA COVID-19-vaccine.
The impact of antenatal massage practice on intrapartum massage application and their associations with the use of analgesics during labour
Authors: Lai Chit Ying , Wong Margaret Kit Wah , Tong Wing Hung , Lau Kam Yan , Chu Suk Yin , Tam Agnes Mei Lee , Hui Lai Ling , Lao Terence T. H. , Leung Tak Yeung 
Published: May 2022

Abstract
Background
Massage during labour is one form of intrapartum non-pharmacological pain relief but it is not known whether the frequency of practicing these massage techniques among couples during the antenatal period could enhance the effectiveness of intrapartum massage. This study was to evaluate the association between compliance of antenatal massage practice with intrapartum application and their impact on the use of analgesics during labour.

Methods
This was a sub-analysis of a childbirth massage programme which was carried out in two public hospitals with total births of around 8000 per year. Data from women who were randomized to the massage group were further analysed. After attending the pre-birth training class on massage at 36 weeks gestation, couples would be encouraged to practice at home. Their compliance with massage at home was classified as good if they had practiced for at least 15 minutes for three or more days in a week, or as poor if the three-day threshold had not been reached. Application of intrapartum massage was quantified by the duration of practice divided by the total duration of the first stage of labour. Women’s application of intrapartum massage were then divided into above and below median levels according to percentage of practice. Logistic regression was used to assess the use of epidural analgesia or pethidine, adjusted for duration of labour and gestational age when attending the massage class.

Results
Among the 212 women included, 103 women (48.6%) achieved good home massage compliance. No significant difference in the maternal characteristics or birth outcomes was observed between the good and poor compliance groups. The intrapartum massage application (median 21.1%) was inversely associated with duration of first stage of labour and positively associated with better home massage practice compliance (p = 0.04). Lower use of pethidine or epidural analgesia (OR 0.33 95% CI 0.12, 0.90) was associated with above median intrapartum massage application but not antenatal massage compliance, adjusted for duration of first stage of labour.

Conclusions
More frequent practice of massage techniques among couples during antenatal period could enhance the intrapartum massage application, which may reduce the use of pethidine and epidural analgesia.

Trial registration
(CCRBCTR) Unique Trial Number CUHK_ CCRB00525.
Pioglitazone and breast cancer risk in female patients with type 2 diabetes mellitus: a retrospective cohort analysis
Authors: Tseng Chin-Hsiao 
Published: May 2022

Abstract
Background
Whether pioglitazone may affect breast cancer risk in female diabetes patients is not conclusive and has not been investigated in the Asian populations.

Methods
The reimbursement database of Taiwan’s National Health Insurance was used to enroll an unmatched cohort and a propensity score-matched cohort of ever users and never users of pioglitazone in female patients with newly diagnosed type 2 diabetes during 1999–2008. The patients were alive on January 1, 2009 and were followed up for breast cancer incidence until December 31, 2011. Cox regression was used to estimate hazard ratios for ever users and tertiles of cumulative duration of pioglitazone therapy versus never users, and for cumulative duration of pioglitazone therapy treated as a continuous variable. Three models were created for the unmatched cohort and the matched cohort, respectively: 1) without adjustment for covariates; 2) after adjustment for covariates that differed with statistical significance (P-value < 0.05) between ever users and never users; and 3) after adjustment for all covariates.

Results
There were 174,233 never users and 6926 ever users in the unmatched cohort; and 6926 never users and 6926 ever users in the matched cohort. After a median follow-up of 2.8 years, the numbers of incident breast cancer were 1044 in never users and 35 in ever users in the unmatched cohort and were 41 and 35, respectively, in the matched cohort. Hazard ratios suggested a null association between pioglitazone and breast cancer in all three models in either the unmatched cohort or the matched cohort. The overall hazard ratio after adjustment for all covariates was 0.758 (95% confidence interval: 0.539–1.065) in the unmatched cohort and was 0.824 (95% confidence interval: 0.524–1.296) in the matched cohort. None of the hazard ratios for the tertiles of cumulative duration of pioglitazone therapy and for the cumulative duration being treated as a continuous variable were statistically significant.

Conclusions
This study suggests a null association between pioglitazone and breast cancer risk in female patients with type 2 diabetes mellitus. However, because of the small breast cancer cases and the limited follow-up time, further studies are warranted to confirm our findings.
Prevalence of child undernutrition measures and their spatio-demographic inequalities in Bangladesh: an application of multilevel Bayesian modelling
Authors: Das Sumonkanti , Baffour Bernard , Richardson Alice 
Published: May 2022

AbstractMicro-level statistics on child undernutrition are highly prioritized by stakeholders for measuring and monitoring progress on the sustainable development goals. In this regard district-representative data were collected in the Bangladesh Multiple Indicator Cluster Survey 2019 for identifying localised disparities. However, district-level estimates of undernutrition indicators - stunting, wasting and underweight - remain largely unexplored. This study aims to estimate district-level prevalence of these indicators as well as to explore their disparities at sub-national (division) and district level spatio-demographic domains cross-classified by children sex, age-groups, and place of residence. Bayesian multilevel models are developed at the sex-age-residence-district level, accounting for cross-sectional, spatial and spatio-demographic variations. The detailed domain-level predictions are aggregated to higher aggregation levels, which results in numerically consistent and reasonable estimates when compared to the design-based direct estimates. Spatio-demographic distributions of undernutrition indicators indicate south-western districts have lower vulnerability to undernutrition than north-eastern districts, and indicate significant inequalities within and between administrative hierarchies, attributable to child age and place of residence. These disparities in undernutrition at both aggregated and disaggregated spatio-demographic domains can aid policymakers in the social inclusion of the most vulnerable to meet the sustainable development goals by 2030.