bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the COVID-19 pandemic on migraine in Japan: a multicentre cross-sectional study
Authors: Suzuki Keisuke , Takeshima Takao , Igarashi Hisaka , Imai Noboru , Danno Daisuke , Yamamoto Toshimasa , Nagata Eiichiro , Haruyama Yasuo , Mitsufuji Takashi , Suzuki Shiho , Ito Yasuo , Shibata Mamoru , Kowa Hisanori , Kikui Shoji , Shiina Tomohiko , Okamura Madoka , Tatsumoto Muneto , Hirata Koichi 
Published: June 2021

Abstract
Objectives
To assess the impacts of social situation changes due to the coronavirus disease 2019 (COVID-19) pandemic on headache-related disability and other symptoms in patients with migraine in Japan.

Methods
We conducted a multicentre, cross-sectional study including 659 outpatients with migraine diagnosed by headache specialists. The participants were asked about the impacts of the first wave of the COVID-19 pandemic on headache-related disability, headache days, headache intensity, stress, physical activity, hospital access and their work and home lives. For headache-related disability, the total Migraine Disability Assessment (MIDAS) score and part A and B scores were analysed. Multivariate stepwise linear regression analysis was performed to identify the clinical predictors of changes in the total MIDAS score before and during the COVID-19 pandemic. Logistic regression analysis was performed to determine the factors related to new-onset headache during the COVID-19 pandemic.

Results
Finally, 606 migraine patients (73 M/533 F; age, 45.2 ± 12.0 years) were included in the study, excluding those with incomplete data. Increased stress, substantial concern about COVID-19 and negative impacts of the first wave of the COVID-19 pandemic on daily life were reported in 56.8 %, 55.1 and 45.0 % of the participants, respectively. The total MIDAS and A and B scores did not significantly change after the first wave of the COVID-19 pandemic. New-onset headache, which was observed in 95 patients (15.7 %), was associated with younger age and worsened mood and sleep in the logistic regression analysis. The multivariate stepwise linear regression analysis of changes in the total MIDAS score before and during the first wave of COVID-19 pandemic identified worsened sleep, increased acute medication use, increased stress, medication shortages, comorbidities, the absence of an aura and new-onset headache were determinants of an increased total MIDAS score during the first wave of the COVID-19 pandemic.

Conclusions
In this multicentre study, clinical factors relevant to headache-related disability, such as new-onset headache, stress and sleep disturbances, were identified, highlighting the importance of symptom management in migraine patients during the first wave of the COVID-19 pandemic.
Lipid polymeric nanoparticles modified with tight junction-modulating peptides promote afatinib delivery across a blood–brain barrier model
Authors: Lo Yu-Li , Lin Hua-Ching , Hong Shu-Ting , Chang Chih-Hsien , Wang Chen-Shen , Lin Anya Maan-Yuh 
Published: June 2021

Abstract
Background
Brain metastases from non-small cell lung cancer (NSCLC) remain one of the most challenging malignancies. Afatinib (Afa) is an orally administered irreversible ErbB family blocker approved for epidermal growth factor receptor (EGFR)-mutated NSCLC. However, the incidence of brain metastases in patients with NSCLC and EGFR mutation is high. One of the major obstacles in the treatment of brain metastases is to transport drugs across the blood–brain barrier (BBB). A lipid polymeric nanoparticle (LPN) modified with a tight junction-modulating peptide is a potential formulation to deliver therapeutics across the BBB. FD7 and CCD are short peptides that perturb the tight junctions (TJs) of the BBB. In this study, the use of LPN modified with FD7 or CCD as a delivery platform was explored to enhance Afa delivery across the BBB model of mouse brain-derived endothelial bEnd.3 cells.

Results
Our findings revealed that Afa/LPN-FD7 and Afa/LPN-CCD exhibited a homogeneous shape, a uniform nano-scaled particle size, and a sustained-release profile. FD7, CCD, Afa/LPN-FD7, and Afa/LPN-CCD did not cause a significant cytotoxic effect on bEnd.3 cells. Afa/LPN-FD7 and Afa/LPN-CCD across the bEnd.3 cells enhanced the cytotoxicity of Afa on human lung adenocarcinoma PC9 cells. FD7 and CCD-modulated TJ proteins, such as claudin 5 and ZO-1, reduced transendothelial electrical resistance, and increased the permeability of paracellular markers across the bEnd.3 cells. Afa/LPN-FD7 and Afa/LPN-CCD were also partially transported through clathrin- and caveolae-mediated transcytosis, revealing the effective activation of paracellular and transcellular pathways to facilitate Afa delivery across the BBB and cytotoxicity of Afa on PC9 cells.

Conclusion
TJ-modulating peptide-modified LPN could be a prospective platform for the delivery of chemotherapeutics across the BBB to the brain for the potential treatment of the BM of NSCLC.
Evolutionary ecology of the visual opsin gene sequence and its expression in turbot (Scophthalmus maximus)
Authors: Wang Yunong , Zhou Li , Wu Lele , Song Changbin , Ma Xiaona , Xu Shihong , Du Tengfei , Li Xian , Li Jun 
Published: June 2021

AbstractBackgroundAs flatfish, turbot undergo metamorphosis as part of their life cycle. In the larval stage, turbot live at the ocean surface, but after metamorphosis they move to deeper water and turn to benthic life. Thus, the light environment differs greatly between life stages. The visual system plays a great role in organic evolution, but reports of the relationship between the visual system and benthic life are rare. In this study, we reported the molecular and evolutionary analysis of opsin genes in turbot, and the heterochronic shifts in opsin expression during development.ResultsOur gene synteny analysis showed that subtypeRH2Cwas not on the same gene cluster as the other four green-sensitive opsin genes (RH2) in turbot. It was translocated to chromosome 8 from chromosome 6. Based on branch-site test and spectral tuning sites analyses, E122Q and M207L substitutions inRH2C, which were found to be under positive selection, are closely related to the blue shift of optimum light sensitivities. And real-time PCR results indicated the dominant opsin gene shifted from red-sensitive (LWS) toRH2B1during turbot development, which may lead to spectral sensitivity shifts to shorter wavelengths.ConclusionsThis is the first report thatRH2Cmay be an important subtype of green opsin gene that was retained by turbot and possibly other flatfish species during evolution. Moreover, E122Q and M207L substitutions inRH2Cmay contribute to the survival of turbot in the bluish colored ocean. And heterochronic shifts in opsin expression may be an important strategy for turbot to adapt to benthic life.
Genome-wide identification of the Capsicum bHLH transcription factor family: discovery of a candidate regulator involved in the regulation of species-specific bioactive metabolites
Authors: Liu Renjian , Song Jiali , Liu Shaoqun , Chen Changming , Zhang Shuanglin , Wang Juntao , Xiao Yanhui , Cao Bihao , Lei Jianjun , Zhu Zhangsheng 
Published: June 2021

Abstract
Background
The basic helix–loop–helix (bHLH) transcription factors (TFs) serve crucial roles in regulating plant growth and development and typically participate in biological processes by interacting with other TFs. Capsorubin and capsaicinoids are found only in Capsicum, which has high nutritional and economic value. However, whether bHLH family genes regulate capsorubin and capsaicinoid biosynthesis and participate in these processes by interacting with other TFs remains unknown.

Results
In this study, a total of 107 CabHLHs were identified from the Capsicum annuum genome. Phylogenetic tree analysis revealed that these CabHLH proteins were classified into 15 groups by comparing the CabHLH proteins with Arabidopsis thaliana bHLH proteins. The analysis showed that the expression profiles of CabHLH009, CabHLH032, CabHLH048, CabHLH095 and CabHLH100 found in clusters C1, C2, and C3 were similar to the profile of carotenoid biosynthesis in pericarp, including zeaxanthin, lutein and capsorubin, whereas the expression profiles of CabHLH007, CabHLH009, CabHLH026, CabHLH063 and CabHLH086 found in clusters L5, L6 and L9 were consistent with the profile of capsaicinoid accumulation in the placenta. Moreover, CabHLH007, CabHLH009, CabHLH026 and CabHLH086 also might be involved in temperature-mediated capsaicinoid biosynthesis. Yeast two-hybrid (Y2H) assays demonstrated that CabHLH007, CabHLH009, CabHLH026, CabHLH063 and CabHLH086 could interact with MYB31, a master regulator of capsaicinoid biosynthesis.

Conclusions
The comprehensive and systematic analysis of CabHLH TFs provides useful information that contributes to further investigation of CabHLHs in carotenoid and capsaicinoid biosynthesis.
Screening and identification of genes affecting grain quality and spikelet fertility during high-temperature treatment in grain filling stage of rice
Authors: Park Jae-Ryoung , Kim Eun-Gyeong , Jang Yoon-Hee , Kim Kyung-Min 
Published: June 2021

Abstract
Background
Recent temperature increases due to rapid climate change have negatively affected rice yield and grain quality. Particularly, high temperatures during right after the flowering stage reduce spikelet fertility, while interfering with sugar energy transport, and cause severe damage to grain quality by forming chalkiness grains. The effect of high-temperature on spikelet fertility and grain quality during grain filling stage was evaluated using a double haploid line derived from another culture of F1 by crossing Cheongcheong and Nagdong cultivars. Quantitative trait locus (QTL) mapping identifies candidate genes significantly associated with spikelet fertility and grain quality at high temperatures.

Results
Our analysis screened OsSFq3 that contributes to spikelet fertility and grain quality at high-temperature. OsSFq3 was fine-mapped in the region RM15749-RM15689 on chromosome 3, wherein four candidate genes related to the synthesis and decomposition of amylose, a starch component, were predicted. Four major candidate genes, including OsSFq3, and 10 different genes involved in the synthesis and decomposition of amylose and amylopectin, which are starch constituents, together with relative expression levels were analyzed. OsSFq3 was highly expressed during the initial stage of high-temperature treatment. It exhibited high homology with FLOURY ENDOSPERM 6 in Gramineae plants and is therefore expected to function similarly.

Conclusion
The QTL, major candidate genes, and OsSFq3 identified herein could be effectively used in breeding rice varieties to improve grain quality, while tolerating high temperatures, to cope with climate changes. Furthermore, linked markers can aid in marker-assisted selection of high-quality and -yield rice varieties tolerant to high temperatures.
Information meetings on end-of-life care for older people by the general practitioner to stimulate advance care planning: a pre-post evaluation study
Authors: van der Plas Annicka G. M. , Pasman H. Roeline W. , Kox Roosmarijne M. K. , Ponstein Marianne , Dame Bea , Onwuteaka-Philipsen Bregje D. 
Published: June 2021

Abstract
Background
To increase knowledge about options people have concerning end-of-life-care issues, General Practitioners (GPs) can organise meetings to inform their older patients. We evaluated these meetings, using the following research questions: How did the attendees experience the information meeting? Was there a rise in Advance Care Planning (ACP) behaviour after the information meeting? Was there a change in trust people have that physicians will provide good care at the end of life and that they will follow their end-of-life wishes after the information meetings?

Methods
Four GPs invited all patients of 75 years and older registered in their GP practices to the meeting via a written letter. Four meetings of 2 h took place in 2016. Meetings started with a presentation on end-of-life topics and ACP by the GP followed by time for questions.
A pre-post evaluation study was done using written questionnaires distributed and filled in at the start of the meeting (T0) at the end of the meeting (T1) and 6 months after the meeting (T2).

Results
In total 225 older people attended a meeting of which 154 (68%) filled in the questionnaire at T0 and 145 (64%) filled in the questionnaire at T1. After six months, 90 of the 121 people who approved of being sent another questionnaire at T2, returned it (40%). The average age of the respondents was 80 years (T0). The meetings were evaluated positively by the attendees (T1). ACP issues (appointing a proxy, resuscitation, hospitalisation, euthanasia, treatment preferences under certain circumstances, preferred place of care and nursing home admittance) were discussed with a physician, a relative or both more often in the 6 months after having attended the meeting (T2), compared to before (T0). Compared to before the meeting (T0), trust in the GP providing good end-of-life care and following end-of-life wishes was higher immediately after the meeting (T1), but not after 6 months (T2).

Conclusion
Information meetings on end-of-life care by GPs have a positive influence on the occurrence of ACP, both with the physician and others. Although, this method especially reaches the older people that are already interested in the subject, this seems a relatively easy way to stimulate ACP.
Frailty increases the risk for developing urinary tract infection among 79,887 patients with diabetic mellitus and chronic kidney disease
Authors: Chao Chia-Ter , Lee Szu-Ying , Wang Jui , Chien Kuo-Liong , Huang Jenq-Wen 
Published: June 2021

Abstract
Background
Patients with diabetic mellitus (DM) and chronic kidney disease (CKD) are at an increased risk of urinary tract infection (UTI) due to their altered immunological integrity. These patients are similarly prone to developing frailty, a state of cumulative health deficits involving multiple domains and leading to adverse outcomes. Whether frailty predisposes affected individuals to UTI among patients with DM and CKD remains unclear.

Methods
A population-based cohort of patients with DM and CKD (n = 79,887) were assembled from the Longitudinal Cohort of Diabetes Patients, with their baseline frailty status measured by a modified FRAIL scale. We analyzed their risk of developing UTI depending on their severity of frailty, after accounting demographic profiles, lifestyle factors, comorbidities, concurrent medications, and major interventions. A secondary analysis focused on the risk of urosepsis related to frailty.

Results
Among all participants, 36.1 %, 50.3 %, 12.8 %, and 0.8 % did not have or had 1, 2, and ≥ 3 FRAIL items, respectively, at baseline. After 3.51 years, 11,175 UTI events occurred. Kaplan-Meier analysis showed that participants with DM, CKD and an increasing number of FRAIL items had successively higher incidence of UTI than those without any FRAIL items (log rank p < 0.001). Cox proportional hazard modeling revealed that after accounting for all confounders, those with more severe frailty exhibited a significantly higher risk of incident UTI (for groups of 1, 2, and ≥ 3 FRAIL items, hazard ratio 1.19, 1.24, and 1.43, respectively; all p < 0.001) than those without. An 11 % risk elevation for UTI could be observed for every FRAIL item increase. Participants with more severe frailty exhibited a trend of having higher risk of urosepsis as well.

Conclusions
Having frailty predicted a higher risk of developing UTI in the future in patients with DM and CKD. It would be prudent to screen for frailty in these patients and provide optimal frailty-directed management to attenuate their risk of UTI and improve their outcomes.
Observation of retinal neovascularization using optical coherence tomography angiography after panretinal photocoagulation for proliferative diabetic retinopathy
Authors: Feng H. E. , Weihong Y. U. , Dong Fangtian 
Published: June 2021

Abstract
Background
To describe the longitudinal changes in retinal neovascularization elsewhere (NVE) as observed on optical coherence tomography angiography (OCTA) in proliferative diabetic retinopathy (PDR) treated by panretinal photocoagulation (PRP).

Methods
Each patient included in this prospective clinical study was newly diagnosed with PDR and NVE confirmed by both fundus fluorescein angiography (FFA) and OCTA. They received four sessions of PRP using a multiwavelength laser. Best-corrected visual acuity (BCVA) and OCTA images of the NVE were obtained before each PRP session and at 1 month, 3 months, and 6 months after the PRP treatment. Generalized estimating equations (GEE) was used to investigate the differences between the BCVA and NVE areas before and after PRP.

Results
Thirty-two eyes of 32 patients with a mean age of 50.56 ± 7.05 years were included. We found a statistically significant reduction in the NVE area at all time points compared with the baseline except at 6 months (all P < 0.05). Further analysis demonstrated no statistically significant change in the NVE area between two adjacent timepoints except from baseline to post-1st PRP (P < 0.05). BCVA at 3 months showed a statistically significant improvement compared with baseline (P < 0.05), but no significant changes in BCVA were observed during the other visits.

Conclusions
We found an overall regression in the NVE area following PRP starting as early as 1 week after the 1st session and lasting up to 3 months. OCTA provides quantitative information on vascular changes and could be a practical method for the longitudinal evaluation of neovascularization.
Cohort study of ageing from Bagé (SIGa-Bagé), Brazil: profile and methodology
Authors: Thumé Elaine , Kessler Marciane , Machado Karla P. , Nunes Bruno P. , Volz Pamela M. , Wachs Louriele S. , Soares Mariangela U. , Saes Mirelle O. , Duro Suele M. , Dilélio Alitéia Santiago , Facchini Luiz A. 
Published: June 2021

Abstract
Background
The Bagé Cohort Study of Ageing is a population-based cohort study that has recently completed the first follow-up of a representative sample of older adults from Bagé, a city with more than 100,000 inhabitants located in the state of Rio Grande do Sul, Brazil. This is one of the first longitudinal studies to assess the impact of primary health care coverage on health conditions and inequalities. Our aim is to investigate the prevalence, incidence and trends of risk factors, health behaviours, social relationships, non-communicable diseases, geriatric diseases and disorders, hospitalisation, self-perceived health, and all-cause and specific-cause mortality. In addition, we aim to evaluate socioeconomic and health inequalities and the impact of primary health care on the outcomes under study.

Methods/design
The study covers participants aged 60 or over, selected by probabilistic (representative) sampling of the urban area of the city of Bagé, which is covered by Primary Health Care Services. The baseline examination included 1593 older adults and was conducted from July 2008 to November 2008. After eight to nine years (2016/2017), the first follow-up was conducted from September 2016 to August 2017. All participants underwent an extensive core assessment programme including structured interviews, questionnaires, cognitive testing (baseline and follow-up), physical examinations and anthropometric measurements (follow-up).

Results
Of the original participants, 1395 (87.6%) were located for follow-up: 757 elderly individuals (47.5%) were re-interviewed, but losses in data transfer occurred for 22. The remaining 638 (40.1%) had died. In addition, we had 81 (5.1%) refusals and 117 (7.3%) losses. Among the 1373 older adults who were followed down, there was a higher proportion of female interviewees (p=0.042) and a higher proportion of male deaths (p=0.001) in 2016/2017. There were no differences in losses and refusals according to gender (p=0.102). There was a difference in average age between the interviewees (68.8 years; SD ±6.5) and non-interviewees (73.2 years; SD ±9.0) (p<0.001). Data are available at the Department of Social Medicine in Federal University of Pelotas, Rio Grande do Sul, Brazil, for any collaboration.
Plantar load transfer in children: a descriptive study with two pathological case studies
Authors: Brierty Alexis , Carty Christopher P. , Giacomozzi Claudia , Phillips Teresa , Walsh Henry P. J. , Bade David , Horan Sean 
Published: June 2021

Abstract
Background
Typical gait is often considered to be highly symmetrical, with gait asymmetries typically associated with pathological gait. Whilst gait symmetry is often expressed in symmetry ratios, measures of symmetry do not provide insight into how these asymmetries affect gait variables. To fully understand changes caused by gait asymmetry, we must first develop a normative database for comparison. Therefore, the aim of this study was to describe normative reference values of regional plantar load and present comparisons with two pathological case studies.

Methods
A descriptive study of the load transfer of plantar pressures in typically developed children was conducted to develop a baseline for comparison of the effects of gait asymmetry in paediatric clinical populations. Plantar load and 3D kinematic data was collected for 17 typically developed participants with a mean age of 9.4 ± 4.0 years. Two case studies were also included; a 10-year-old male with clubfoot and an 8-year-old female with a flatfoot deformity. Data was analysed using a kinematics-pressure integration technique for anatomical masking into 5 regions of interest; medial and lateral forefoot, midfoot, and medial and lateral hindfoot.

Results
Clear differences between the two case studies and the typical dataset were seen for the load transfer phase of gait. For case study one, lateral bias was seen in the forefoot of the trailing foot across all variables, as well as increases in contact area, force and mean pressure in the lateral hindfoot of the leading foot. For case study two, the forefoot of the trailing foot produced results very similar to the typical dataset across all variables. In the hindfoot of the leading foot, medial bias presents most notably in the force and mean pressure graphs.

Conclusions
This study highlights the clinical significance of the load transfer phase of gait, providing meaningful information for intervention planning.
An accurate method of measuring shoulder sling compliance: a validation study
Authors: Sood Anshum , Klein Ashley , Kaveeshwar Samir , Jones Derek L. , Duvall Grant , Hovis James Paul , Weir Tristan B. , Enobun Blessing , Hasan S. Ashfaq , Henn R. Frank , Packer Jonathan D. , Gilotra Mohit N. 
Published: June 2021

Abstract
Background
The effect of postoperative shoulder sling compliance on surgical outcomes is unknown. The goal was to determine an accurate method to measure sling compliance. We compared volunteer recorded sling wear time with temperature-based sensors to monitor sling compliance.

Methods
Data loggers sutured at three locations measured heat generated in 15-minute intervals. Slings wearers logged sling wear to accurately cross-reference with temperature sensors. Secondary experiments analyzed whether surrounding ambient temperature can be discerned from actual sling wear. We created an algorithm to describe actual sling wear time as a function of heat recorded and calculated percent wear accuracy.

Results
The modified sling was worn for 172 h. The algorithm modeled sling on/off times by analyzing cutoff temperatures. Diagnostic accuracy was >99 % for the three locations, with no statistically significant differences among them. Compared with sling wear, ambient temperature took longer to reach critical temperature values determined by the algorithm, helping distinguish compliance from false positives.

Conclusions
The described algorithm can effectively quantify shoulder sling wear time based on heat-generated sensor readings. False positives from ambient temperature are minimal. This measurement method could be used to study the relationship between postoperative sling use and functional outcomes after shoulder surgery.