bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-line therapy for metastatic renal cell carcinoma
Authors: Sawhney Paramvir , Suyanto Suyanto , Michael Agnieszka , Pandha Hardev 
Published: May 2022

Objectives: To evaluate current first-line treatment strategies in advanced or metastatic renal cell carcinoma (RCC), and to review other promising treatments under investigations. Materials and methods: We reviewed all relevant pivotal first-line systemic therapy trials, and studies investigating the role of cytoreductive nephrectomy, metastectomy, and ablative radiotherapy in advanced or metastatic RCC. Results: In total we identified 21 relevant studies, investigating both systemic and non-systemic therapies, including treatments under investigations. Conclusion: Metastatic RCC (mRCC) is a highly heterogeneous disease that is notoriously difficult to treat, however, the discovery of novel targeted therapies over the past decade have revolutionised its management. The International mRCC Database Consortium (IMDC) is a prognostic model that is commonly used in both clinical trials and routine clinical care to risk-stratify patients with mRCC, which has helped with therapy selection for mRCC patients over the past decade. However, with an improved understanding of tumour biology and genetics, this has prompted a shift from cytokine therapy to receptor tyrosine kinase inhibitors, and now to Immune Checkpoint Inhibitors (ICIs). Recent promising results from clinical studies with ICI combination treatments have transformed the treatment landscape for the management of intermediate- and poor- risk clear cell RCC, however, further research is still needed for favourable-risk, and non-clear cell patients. Level of evidence: Not applicable
Stress-Buffering Effects of Mindfulness Programming for Adolescents in Schools During Periods of High- and Low-Stress
Authors: Helminen Emily C. , Zhang (张晓燕) Xiaoyan , Clawson Adam J. , Morton Melissa L. , Cary Emily L. , Sinegar Samantha E. , Janack Pamela , Felver Joshua C. 
Published: May 2022

Purpose Stress is a risk factor for poor educational achievement and health. Mindfulness-based programming (MBP) is a viable technology for reducing stress, and Mindful Stress Buffering theory suggests that the benefits of MBP will be most pronounced during periods of high stress. This research details a replication of the MBP “Learning to BREATHE” in a racially diverse urban public high school during a period of relatively low stress (i.e., absence of high-stakes testing). Design/Approach/Methods Five classrooms ( n = 66) were randomly assigned by classroom to MBP or typical educational programming. Socioemotional attributes were measured pre–post-intervention. Data were contrasted with results from the initial project that occurred during a period of high stress (i.e., the presence of high-stakes testing). Findings Results indicate a failure to replicate significant intervention effects of MBP on socioemotional attributes. Results indicate that the original Felver et al.’s (2019) sample had higher self-reported stress than the current study's sample. Originality/Value These findings provide the first empirical data in support of the Mindful Stress Buffering theory among an adolescent sample, and this has implications for clinicians and researchers interested in utilizing MBP to support the wellbeing of student populations during other periods of high contextual stress (e.g., COVID-19 pandemic).
Dietary oily fish intake and progression of diffuse subcortical damage of vascular origin: A longitudinal prospective study in community-dwelling older adults
Authors: Del Brutto Oscar H , Mera Robertino M , Del Brutto Victor J , Recalde Bettsy Y , Rumbea Denisse A , Sedler Mark J 
Published: May 2022

Introduction: Oily fish intake may reduce the progression of white matter hyperintensities (WMH) of presumed vascular origin due to their high content of omega-3 polyunsaturated fatty acids and other nutrients. However, information on this relationship is limited. We aimed to assess the association between oily fish intake and WMH progression in older adults living in rural coastal Ecuador. Methods: Participants of the Atahualpa Project Cohort received baseline clinical interviews and brain MRIs. Oily fish intake was calculated at every annual door-to-door survey from enrollment to the end of the study. Individuals who also received a follow-up brain MRI were included. Poisson regression models were fitted to assess the incidence rate ratio (IRR) of WMH progression according to the amount of oily fish intake, after adjusting for demographics, level of education and traditional vascular risk factors. Results: The study included 263 individuals of Amerindian ancestry aged ⩾60 years (mean age: 65.7 ± 6.2 years; 57% women). The mean oily fish intake was 8.3 ± 4 servings per week. Follow-up MRIs demonstrated WMH progression in 103 (39%) individuals after a median follow-up of 6.5 years. A multivariate Poisson regression model showed an inverse relationship between oily fish intake and WMH progression (IRR: 0.89; 95% CI: 0.84–0.95; p < 0.001). A similar model also revealed an inverse relationship between tertiles of oily fish intake and probabilities of WMH progression, which became significant when individuals allocated to the third tertile were compared to those in the first and second tertiles. Conclusion: Study results show an inverse relationship between the amount of oily fish intake and WMH progression in frequent fish consumers of Amerindian ancestry.
Addressing the Temporal Constraint in Sagittal Synostosis: Modification of the Extended Suturectomy Technique
Authors: Kurnik Nicole M. , Pflibsen Lacey R. , Howarth Ashley L. , Walton Mollie M. , Bristol Ruth E. , Beals Stephen P. , Shafron David H. , Singh Davinder J. 
Published: May 2022

Introduction: Numerous surgical techniques have been described for correction of sagittal synostosis. However, many do not address the often-persistent temporal constraint. To address the deformity, the endoscopic surgical technique used at this institution was modified to include frontal bone releasing osteotomies across the coronal sutures in the area of the temporal constraint. The purpose of this study was to evaluate the early benefit of this technique. Methods: A retrospective review of electronic health records was performed for 31 consecutive patients who received frontal bone releasing osteotomies and 33 consecutive patients before frontal bone releasing osteotomies were initiated in May of 2015. Both cohorts were age matched and underwent the same postsurgical orthotic therapy protocol. The Whitaker classification system and a visual analog scale were used to evaluate for temporal constraint. Images were reviewed at 6 months after the postsurgical orthotic was removed. Results: Patients who received frontal bone releasing osteotomies had significantly improved Whitaker grade scores (1.27 vs 1.64, P < .05) and greater improvement in visual analog scores (39.97 vs 25.64, P < .05) compared with those who did not. Both ratings showed good interrater reliability. Conclusions: During the early postsurgical period, greater and more rapid improvement in the temporal constraint was seen in the group of patients who had additional frontal bone releasing osteotomies during the correction of sagittal synostosis. Longer-term follow-up is needed to evaluate maintenance of the improvement as relapse and poor growth in this area are known to occur.
Implications of COVID-19 for future travel behaviour in the rural periphery
Authors: Nelson John D. , Caulfield Brian 
Published: May 2022

Abstract
Background
The design, management and operation of transport systems is a complex activity and this has only been exacerbated since the onset of the COVID-19 pandemic. Concern has been raised over the likelihood of the public transport sector surviving in some locations given the significant drops in patronage; this is especially so in rural environments where the existing provision was already limited. Furthermore, within the growing literature on the impact of COVID-19 on travel behaviour most of the focus is on urban areas with little documented experience of how rural travel behaviour has been impacted.

Purpose
This paper investigates the impact of COVID-19 on the transport sector and travel behaviour in the rural periphery.

Methods
Drawing on the work of the International Transport Forum (ITF) Working Group on Innovative Mobility for the Periphery, augmented by additional evidence and findings from the literature, this paper addresses three specific questions: Firstly, how COVID-19 has affected rural mobility. Secondly, how we can plan for sustainable rural transport solutions in the post-COVID world. Thirdly, the longer-term impacts of COVID-19 with implications for mobility.

Results
There will be substantial impacts from COVID-19 on rural societies and while the short-term impacts have been negative, in the longer-term there may be opportunity for changed mobility behaviours (including in response to modified work and activity patterns). Evidence suggests that it would seem likely that there are opportunities to foster new rural mobility solutions to support sustainable mobility (including Mobility-as-a-Service) and counter the traditionally fragmented transport base; this will be important as we learn to live with COVID-19.

Conclusions
While recognising the impact of changing funding priorities and the possible shift in economic activity as a result of the pandemic we conclude with suggestions for future rural transport policy.
Functional analysis of PagNAC045 transcription factor that improves salt and ABA tolerance in transgenic tobacco
Authors: Zhang Xuemei , Cheng Zihan , Fan Gaofeng , Yao Wenjing , Li Wei , Chen Sixue , Jiang Tingbo 
Published: May 2022

Abstract
Background
Salt stress causes inhibition of plant growth and development, and always leads to an increasing threat to plant agriculture. Transcription factors regulate the expression of various genes for stress response and adaptation. It’s crucial to reveal the regulatory mechanisms of transcription factors in the response to salt stress.

Results
A salt-inducible NAC transcription factor gene PagNAC045 was isolated from Populus alba×P. glandulosa. The PagNAC045 had a high sequence similarity with NAC045 (Potri.007G099400.1) in P. trichocarpa, and they both contained the same conserved motifs 1 and 2, which constitute the highly conserved NAM domain at the N-terminus. Protein-protein interaction (PPI) prediction showed that PagNAC045 potentially interacts with many proteins involved in plant hormone signaling, DNA-binding and transcriptional regulation. The results of subcellular localization and transient expression in tobacco leaves confirmed the nuclear localization of PagNAC045. Yeast two-hybrid revealed that PagNAC045 protein exhibits transcriptional activation property and the activation domain located in its C-terminus. In addition, the 1063 bp promoter of PagNAC045 was able to drive GUS gene expression in the leaves and roots. In poplar leaves and roots, PagNAC045 expression increased significantly by salt and ABA treatments. Tobacco seedlings overexpressing PagNAC045 exhibited enhanced tolerance to NaCl and ABA compared to the wild-type (WT). Yeast one-hybrid assay demonstrated that a bHLH104-like transcription factor can bind to the promoter sequence of PagNAC045.

Conclusion
The PagNAC045 functions as positive regulator in plant responses to NaCl and ABA-mediated stresses.
Influence of different regimens of volumetric therapy on perioperative intestinal flora in the surgical patients with pancreas tumor, a randomized controlled trial study
Authors: Lu Xiaojian , Wang Ying , Luo Yan , Yu Buwei 
Published: May 2022

Abstract
Background
It is not clear whether the perioperative intestinal microenvironment of patients undergoing pancreatic tumor surgery is affected by intraoperative fluid therapy.

Method
Fifty-eight patients who underwent a confined excision of pancreas mass at this center were enrolled. The patients were grouped according to the random number table in these two groups: the liberal fluid infusion (LFI) group and the goal-directed fluid therapy (GDFT) group. Perioperative anesthesia management was carried out by the same team of anesthesiologists according to a preset anesthetic protocol. Fecal samples were collected twice: within 2 days before the surgery and at 6 to 8 days postoperatively. The collected fecal samples were sequenced through microbial diversity high-throughput 16 s-rDNA; and the differential changes of intestinal flora were analyzed.

Results
Main components of flora in the sample were significantly different between LFI and GDFT groups. As shown by the difference in species, in GDFT group, more constituent bacteria participated in the metabolism inside human body and the restoration of coagulation function, including: prevotella, roseburia, lachnospiracea, dialister and clostridium (P < 0.05); in LFI group, more constituent bacteria were opportunistic pathogenic bacteria, including: enterococcus, pseudomonas aeruginosa, and acinetobacter baumannii (P < 0.05).

Conclusion
For surgical patients with pancreas tumor, there are significant differences of intestinal flora in diversity between GDFT and LFI. GDFT seems to play a more important role in protection and restoration of intestinal flora.

Clinical trial registration
ChiCTR2000035187.
COVID-19 in Japan, January–March 2020: insights from the first three months of the epidemic
Authors: Imai Natsuko , Gaythorpe Katy A. M. , Bhatia Sangeeta , Mangal Tara D. , Cuomo-Dannenburg Gina , Unwin H. Juliette T. , Jauneikaite Elita , Ferguson Neil M. 
Published: May 2022

Abstract
Background
Understanding the characteristics and natural history of novel pathogens is crucial to inform successful control measures. Japan was one of the first affected countries in the COVID-19 pandemic reporting their first case on 14 January 2020. Interventions including airport screening, contact tracing, and cluster investigations were quickly implemented. Here we present insights from the first 3 months of the epidemic in Japan based on detailed case data.

Methods
We conducted descriptive analyses based on information systematically extracted from individual case reports from 13 January to 31 March 2020 including patient demographics, date of report and symptom onset, symptom progression, travel history, and contact type. We analysed symptom progression and estimated the time-varying reproduction number, Rt, correcting for epidemic growth using an established Bayesian framework. Key delays and the age-specific probability of transmission were estimated using data on exposures and transmission pairs.

Results
The corrected fitted mean onset-to-reporting delay after the peak was 4 days (standard deviation: ± 2 days). Early transmission was driven primarily by returning travellers with Rt peaking at 2.4 (95% CrI: 1.6, 3.3) nationally. In the final week of the trusted period (16–23 March 2020), Rt accounting for importations diverged from overall Rt at 1.1 (95% CrI: 1.0, 1.2) compared to 1.5 (95% CrI: 1.3, 1.6), respectively. Household (39.0%) and workplace (11.6%) exposures were the most frequently reported potential source of infection. The estimated probability of transmission was assortative by age with individuals more likely to infect, and be infected by, contacts in a similar age group to them. Across all age groups, cases most frequently onset with cough, fever, and fatigue. There were no reported cases of patients < 20 years old developing pneumonia or severe respiratory symptoms.

Conclusions
Information collected in the early phases of an outbreak are important in characterising any novel pathogen. The availability of timely and detailed data and appropriate analyses is critical to estimate and understand a pathogen’s transmissibility, high-risk settings for transmission, and key symptoms. These insights can help to inform urgent response strategies.
Prediction and analysis of COVID-19 daily new cases and cumulative cases: times series forecasting and machine learning models
Authors: Wang Yanding , Yan Zehui , Wang Ding , Yang Meitao , Li Zhiqiang , Gong Xinran , Wu Di , Zhai Lingling , Zhang Wenyi , Wang Yong 
Published: May 2022

Abstract
Background
COVID-19 poses a severe threat to global human health, especially the USA, Brazil, and India cases continue to increase dynamically, which has a far-reaching impact on people's health, social activities, and the local economic situation.

Methods
The study proposed the ARIMA, SARIMA and Prophet models to predict daily new cases and cumulative confirmed cases in the USA, Brazil and India over the next 30 days based on the COVID-19 new confirmed cases and cumulative confirmed cases data set(May 1, 2020, and November 30, 2021) published by the official WHO, Three models were implemented in the R 4.1.1 software with forecast and prophet package. The performance of different models was evaluated by using root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE).

Results
Through the fitting and prediction of daily new case data, we reveal that the Prophet model has more advantages in the prediction of the COVID-19 of the USA, which could compose data components and capture periodic characteristics when the data changes significantly, while SARIMA is more likely to appear over-fitting in the USA. And the SARIMA model captured a seven-day period hidden in daily COVID-19 new cases from 3 countries. While in the prediction of new cumulative cases, the ARIMA model has a better ability to fit and predict the data with a positive growth trend in different countries(Brazil and India).

Conclusions
This study can shed light on understanding the outbreak trends and give an insight into the epidemiological control of these regions. Further, the prediction of the Prophet model showed sufficient accuracy in the daily COVID-19 new cases of the USA. The ARIMA model is suitable for predicting Brazil and India, which can help take precautions and policy formulation for this epidemic in other countries.
Differing clinical features between Japanese siblings with cerebrotendinous xanthomatosis with a novel compound heterozygous CYP27A1 mutation: a case report
Authors: Koyama Shingo , Okabe Yuma , Suzuki Yuya , Igari Ryosuke , Sato Hiroyasu , Iseki Chifumi , Tanji Kazuyo , Suzuki Kyoko , Ohta Yasuyuki 
Published: May 2022

Abstract
Background
Cerebrotendinous xanthomatosis (CTX) is an autosomal-recessive lipid storage disorder caused by mutations in the CYP27A1 gene encoding the key enzyme in the bile acid synthesis, sterol 27-hydroxylase. Here, we report two Japanese CTX siblings with a novel compound heterozygous CYP27A1 mutation, showing different clinical phenotypes and responses to chenodeoxycholic acid (CDCA) therapy.

Case presentation
The proband, a 32-year-old man, who had chronic diarrhea, bilateral cataracts, and xanthomas, demonstrated progressive neurological manifestations including ataxia, and spastic paraplegia during a 5-year follow-up period despite normalization of serum cholestanol after initiation of CDCA treatment. He also exhibited cognitive decline although improvement had been observed at the beginning of treatment. Follow-up brain magnetic resonance imaging (MRI) revealed pronounced progressive atrophy in the cerebellum, in addition to expanding hyperintense lesions in the dentate nuclei, posterior limb of the internal capsule, cerebral peduncles, and inferior olives on T2-weighted images. In contrast, the two-year-younger sister of the proband presented with chronic diarrhea, cataracts, xanthomas, and intellectual disability but no other neurological symptoms at the time of diagnosis. CDCA treatment lead to improvement of cognitive function and there were no characteristic CTX-related MRI features during the follow-up period. The siblings shared a paternally inherited c.1420C > T mutation (p.Arg474Trp) and a maternally inherited novel c.1176_1177delGA mutation, predicting p.(Glu392Asp*20).

Conclusions
Our cases suggest that early diagnosis and subsequent initiation of CDCA treatment are crucial before the appearance of characteristic MRI findings and severe neurological manifestations related to CTX. Further studies are required to elucidate mechanisms responsible for the clinical diversity of CTX and prognostic factors for long-term outcomes following initiation of CDCA treatment.
Technical innovations in stroke rehabilitation – a survey for development of a non-invasive, brainwave-guided, functional muscle stimulation
Authors: Liebl Stefanie , Tischendorf Tim , Winterlich Julia , Schaal Tom 
Published: May 2022

Abstract
Background
Stroke is one of the most frequent causes of death in Germany and the developed countries. After a stroke, those affected often suffer particularly from functional motor restrictions of the upper extremities. Newer techniques such as the BCI-FES systems aim to establish a communication channel between the brain and external devices with a neuromuscular intervention. The electrical activity of the brain is measured, processed, translated into control signals and can then be used to control an application.

Methods
As a mixed-methods design (exploratory design), eight guideline-based expert interviews were conducted first. For the quantitative expert survey, 95 chief physicians from the field of neuromedicine in rehabilitation facilities nationwide were subsequently invited to participate in an online survey.

Results
In our data analysis, we found that doctors are largely open-minded towards new technical rehabilitation systems. In addition to the proper functioning of the system, they consider the understanding of the functionality and the meaningfulness of the system to be particularly important. In addition, the system should be motivating for individuals, generate meaningful movements, be easy to use, evidence-based and quick to set up. Concerns were expressed regarding the understanding of the system’s processes, especially in the acute phase after a stroke, as well as the excessive expectation of results from the system on the part of the persons. The experts named stroke patients in rehabilitation phase C, which is about mobilization and recovery, as well as all persons who can understand the language requirements as benefiting groups of people.

Conclusion
The present study shows that more research should and must be done in the field of BCI-FES interfaces, and various development trends have been identified. The system has the potential to play a leading role in the rehabilitation of stroke patients in the future. Nevertheless, more work should be done on the improvement and implementation as well as the system’s susceptibility to interference in everyday patient life.