bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early use of acute medication for preventing migraine attacks: Results from a diary-based cohort study
Authors: Termini Susanna Di , Wöber Christian , Brannath Werner 
Published: August 2020

Background: Treating migraine attacks early may improve outcome. The aim of this analysis was to investigate whether certain premonitory symptoms could be indicators for taking acute medication. Methods: We analyzed 3-month diary data recorded by 271 patients with episodic migraine and looked at all migraine-free intervals. For investigating the interaction between acute medication and neck discomfort associated with sensitivity to lights, noises, or odors, we used a marginal structural model and a Cox regression analysis adjusted for moderate or severe headache. Results: The patients (mean age 43 ± 15.4 years, 88% women) recorded a total of 20,219 diary days without migraine. In the marginal structural model analysis, the risk for occurrence of a migraine attack on the subsequent day was reduced when acute medication was used in the presence of neck discomfort associated with sensitivity to lights (hazard ratio 0.4; 95% confidence interval 0.2–0.7), noises (0.4; 0.3–0.7), or odors (0.2; 0.1–0.4). The marginal structural model showed lower risk of migraine attacks than the Cox regression analysis adjusted for moderate or severe headache in the majority of the cases. Conclusion: Migraine attacks may be prevented when acute medication is used in the presence of neck discomfort associated with sensitivity to lights, noises, or odors. The results of this study may stimulate further prospective trials.
HAK/KUP/KT family potassium transporter genes are involved in potassium deficiency and stress responses in tea plants (Camellia sinensis L.): expression and functional analysis
Authors: Yang Tianyuan , Lu Xin , Wang Yan , Xie Yunxia , Ma Jingzhen , Cheng Xunmin , Xia Enhua , Wan Xiaochun , Zhang Zhaoliang 
Published: August 2020

Abstract
Background
Tea plant is one of the most important non-alcoholic beverage crops worldwide. While potassium (K+) is an essential macronutrient and greatly affects the growth and development of plants, the molecular mechanism underlying K+ uptake and transport in tea plant root, especially under limited-K+ conditions, is still poorly understood. In plants, HAK/KUP/KT family members play a crucial role in K+ acquisition and translocation, growth and development, and response to stresses. Nevertheless, the biological functions of these genes in tea plant are still in mystery, especially their roles in K+ uptake and stress responses.

Results
In this study, a total of 21 non-redundant HAK/KUP/KT genes (designated as CsHAKs) were identified in tea plant. Phylogenetic and structural analysis classified the CsHAKs into four clusters (I, II, III, IV), containing 4, 8, 4 and 5 genes, respectively. Three major categories of cis-acting elements were found in the promoter regions of CsHAKs. Tissue-specific expression analysis indicated extremely low expression levels in various tissues of cluster I CsHAKs with the exception of a high root expression of CsHAK4 and CsHAK5, a constitutive expression of clusters II and III CsHAKs, and a moderate cluster IV CsHAKs expression. Remarkably, the transcript levels of CsHAKs in roots were significantly induced or suppressed after exposure to K+ deficiency, salt and drought stresses, and phytohormones treatments. Also notably, CsHAK7 was highly expressed in all tissues and was further induced under various stress conditions. Therefore, functional characterization of CsHAK7 was performed, and the results demostrated that CsHAK7 locates on plasma membrane and plays a key role in K+ transport in yeast. Taken together, the results provide promising candidate CsHAKs for further functional studies and contribute to the molecular breeding for new tea plants varieties with highly efficient utilization of K+.

Conclusion
This study demonstrated the first genome-wide analysis of CsHAK family genes of tea plant and provides a foundation for understanding the classification and functions of the CsHAKs in tea plants.
Differences in patient population and service provision between nurse practitioner and general practitioner consultations in Swiss primary care: a case study
Authors: Gysin Stefan , Meier Rahel , van Vught Anneke , Merlo Christoph , Gemperli Armin , Essig Stefan 
Published: August 2020

AbstractBackgroundPrimary care systems around the world have implemented nurse practitioners (NPs) to ensure access to high quality care in times of general practitioner (GP) shortages and changing health care needs of a multimorbid, ageing population. In Switzerland, NPs are currently being introduced, and their exact role is yet to be determined. The aim of this study was to get insight into patient characteristics and services provided in NP consultations compared to GP consultations in Swiss primary care.MethodsThis case study used retrospective observational data from electronic medical records of a family practice with one NP and two GPs. Data on patient-provider encounters were collected between August 2017 and December 2018. We used logistic regression to assess associations between the assignment of the patients to the NP or GP and patient characteristics and delivered services respectively.ResultsData from 5210 patients participating in 27,811 consultations were analyzed. The average patient age was 44.3 years (SD 22.6), 47.1% of the patients were female and 19.4% multimorbid. 1613 (5.8%) consultations were with the NP, and 26,198 (94.2%) with the two GPs. Patients in NP consultations were more often aged 85+ (OR 3.43; 95%-CI 2.70–4.36), multimorbid (OR 1.37; 95%-CI 1.24–1.51;p < 0.001) and polypharmaceutical (OR 1.28; 95%-CI 1.15–1.42; p < 0.001) in comparison to GP consultations. In NP consultations, vital signs (OR 3.05; 95%-CI 2.72–3.42;p < 0.001) and anthropometric data (OR 1.33; 95%-CI 1.09–1.63; p 0.005) were measured more frequently, and lab tests (OR 1.16; 95%-CI 1.04–1.30; p 0.008) were ordered more often compared to GP consultations, independent of patient characteristics. By contrast, medications (OR 0.35; 95%-CI 0.30–0.41; p < 0.001) were prescribed or changed less frequently in NP consultations.ConclusionsQuantitative data from pilot projects provide valuable insights into NP tasks and activities in Swiss primary care. Our results provide first indications that NPs might have a focus on and could offer care to the growing number of multimorbid, polypharmaceutical elderly in Swiss primary care.
Interaction between lead and noradrenergic genotypes affects neurocognitive functions in attention-deficit/hyperactivity disorder: a case control study
Authors: Choi Jae-Won , Jung A-Hyun , Nam Sojeong , Kim Kyoung Min , Kim Jun Won , Kim Soo Yeon , Kim Bung-Nyun , Kim Jae-Won 
Published: August 2020

Abstract
Background
Lead is known to be associated with attention-deficit/hyperactivity disorder (ADHD) even at low concentrations. We aimed to evaluate neurocognitive functions associated with lead in the blood and the interactions between lead and dopaminergic or noradrenergic pathway-related genotypes in youths with ADHD.

Methods
A total of 259 youths with ADHD and 96 healthy controls (aged 5–18 years) enrolled in this study. The Korean Kiddie Schedule for Affective Disorders and Schizophrenia–Present and Lifetime version was conducted for psychiatric diagnostic evaluation. Blood lead levels were measured, and their interaction with dopaminergic or noradrenergic genotypes for ADHD; namely, the dopamine transporter (DAT1), dopamine receptor D4 (DRD4), and alpha-2A-adrenergic receptor (ADRA2A) genotypes were investigated. All participants were assessed using the ADHD Rating Scale-IV (ADHD-RS). Participants also completed the continuous performance test (CPT) and Stroop Color-Word Test (SCWT). Analysis of covariance was used for comparison of blood lead levels between ADHD and control groups. A multivariable linear regression model was used to evaluate the associations of blood lead levels with the results of ADHD-RS, CPT, and SCWT; adjusted for intelligence quotient (IQ), age, and sex. A path analysis model was used to identify the mediating effects of neurocognitive functions on the effects of blood lead on ADHD symptoms. To evaluate the effect of the interaction between blood lead and genes on neuropsychological functions, hierarchical regression analyses were performed.

Results
There was a significant difference in blood lead levels between the ADHD and control groups (1.4 ± 0.5 vs. 1.3 ± 0.5 μg/dL, p = .005). Blood lead levels showed a positive correlation with scores on omission errors(r = .158, p = .003) and response time variability (r = .136, p = .010) of CPT. In the multivariable linear regression model, blood lead levels were associated with omission errors (B = 3.748, p = .045). Regarding the effects of lead on ADHD symptoms, hyperactivity-impulsivity was mediated by omission errors. An interaction effect was detected between ADRA2A DraI genotype and lead levels on omission errors (B = 5.066, p = .041).

Conclusions
Our results indicate that neurocognitive functions at least partly mediate the association between blood lead levels and ADHD symptoms, and that neurocognitive functions are affected by the interaction between blood lead levels and noradrenergic genotype.
The effect of bone cement distribution on the outcome of percutaneous Vertebroplasty: a case cohort study
Authors: Tan Lei , Wen Bingtao , Guo Zhaoqing , Chen Zhongqiang 
Published: August 2020

Abstract
Background
To analyze the effect of different types of bone cement distribution after percutaneous vertebroplasty (PVP) in patients with osteoporotic vertebral compression fracture (OVCF).

Methods
One hundred thirty seven patients with single level OVCF who underwent PVP were retrospectively analyzed. The patients were divided into two groups according to bone cement distribution. Group A: bone cement contacted both upper and lower endplates; Group B: bone cement missed at least one endplate. Group B was divided into 3 subgroups. Group B1: bone cement only contacted the upper endplates; Group B2: bone cement only contacted the lower endplates; Group B3: bone cement only located in the middle of vertebral body. The visual analogue scale (VAS) score at 24 h post operation and last follow-up, anterior vertebral height restoration ratio (AVHRR), anterior vertebral height loss ratio (AVHLR), local kyphotic angle change and vertebral body recompression rate were compared.

Results
24 h post operation, the pain of all groups were significantly improved. The average follow-up time was 15.3 ± 6.3 (6–24) months. At last follow-up, the VAS score of group A was lower than that of group B. There were 14 cases (10.2%) of adjacent vertebral fracture, 5 cases (8.6%) in group A and 9 cases (11.4%) in group B. There were 9 cases (6.6%) of cement leakage, 4 cases (6.9%) in group A and 5 cases (6.3%) in group B. At last follow-up, there were 16 cases (11.7%) of vertebral body recompression, including 3 cases (5.2%) in group A and 13 cases (16.5%) in group B. There was no significant difference in AVHRR between two groups. Local kyphotic angle change was significant larger in group B. At last follow-up, AVHLR in group B was higher than that in group A. Analysis in subgroup B revealed no significant difference in VAS score, local kyphotic angle change, vertebral recompression rate, AVHRR or AVHLR.

Conclusions
If the bone cement fully contacted both the upper and lower endplates, it can better restore the strength of the vertebral body and maintain the height of the vertebral body, reduce the risk of the vertebral body recompression and long-term pain.
Transient osteoporosis of the hip and subclinical hypothyroidism: an unusual dangerous duet? Case report and pathogenetic hypothesis
Authors: Paoletta Marco , Moretti Antimo , Liguori Sara , Bertone Matteo , Toro Giuseppe , Iolascon Giovanni 
Published: August 2020

Abstract
Background
Transient osteoporosis of the hip (TOH) is a rare and temporary clinical condition characterised by bone marrow edema (BME), severe pain, and functional limitation. It commonly occurs in middle-aged men or in women in the last trimester of pregnancy. TOH usually resolves with conservative therapy but may predispose to hip fracture or progression to avascular necrosis (AVN). Etiology is still unclear, although several pathophysiological mechanisms underpinning this condition has been proposed. We describe the management of an unusual case of TOH occurred in a patient with subclinical hypothyroidism.

Case presentation
A clinical case of a 46-year-old man with severe pain in the left anterior thigh is presented. After a comprehensive clinical and radiological approach, a TOH was diagnosed. Moreover, biochemical assessment suggested the presence of subclinical hypothyroidism. After 3 months of treatment with clodronate, physical therapy and hormone replacement therapy (HRT) a significant improvement of clinical and radiological outcomes was observed.

Conclusion
Several pathological conditions have been related to development of TOH. In our case, we suggested for the first time a role of subclinical hypothyroidism as novel contributory factor for the onset of this condition, providing pathophysiological mechanisms and a scientific rationale for pharmacological treatment.
Reengineering anthrax toxin protective antigen for improved receptor-specific protein delivery
Authors: Becker Lukas , Verdurmen Wouter P. R. , Plückthun Andreas 
Published: August 2020

Abstract
Background
To increase the size of the druggable proteome, it would be highly desirable to devise efficient methods to translocate designed binding proteins to the cytosol, as they could specifically target flat and hydrophobic protein-protein interfaces. If this could be done in a manner dependent on a cell surface receptor, two layers of specificity would be obtained: one for the cell type and the other for the cytosolic target. Bacterial protein toxins have naturally evolved such systems. Anthrax toxin consists of a pore-forming translocation unit (protective antigen (PA)) and a separate protein payload. When engineering PA to ablate binding to its own receptor and instead binding to a receptor of choice, by fusing a designed ankyrin repeat protein (DARPin), uptake in new cell types can be achieved.

Results
Prepore-to-pore conversion of redirected PA already occurs at the cell surface, limiting the amount of PA that can be administered and thus limiting the amount of delivered payload. We hypothesized that the reason is a lack of a stabilizing interaction with wild-type PA receptor. We have now reengineered PA to incorporate the binding domain of the anthrax receptor CMG2, followed by a DARPin, binding to the receptor of choice. This construct is indeed stabilized, undergoes prepore-to-pore conversion only in late endosomes, can be administered to much higher concentrations without showing toxicity, and consequently delivers much higher amounts of payload to the cytosol.

Conclusion
We believe that this reengineered system is an important step forward to addressing efficient cell-specific delivery of proteins to the cytosol.
Assessing inequalities and regional disparities in child nutrition outcomes in India using MANUSH – a more sensitive yardstick
Authors: Jain Ayushi , Agnihotri Satish B. 
Published: August 2020

AbstractBackgroundIndia is strongly committed to reducing the burden of child malnutrition, which has remained a persistent concern. Findings from recent surveys indicate co-existence of child undernutrition, micronutrient deficiency and overweight/obesity, i.e. the triple burden of malnutrition among children below 5 years. While considerable efforts are being made to address this challenge, and several composite indices are being explored to inform policy actions, the methodology used for creating such indices, i.e., linear averaging, has its limitations. Briefly put, it could mask the uneven improvement across different indicators by discounting the ‘lagging’ indicators, and hence not incentivising a balanced improvement. Signifying negative implications on policy discourse for improved nutrition. To address this gap, we attempt to develop a composite index for estimating the triple burden of malnutrition in India, using a more sensitive measure, MANUSH.MethodologyData from publicly available nation-wide surveys - National Family Health Survey (NFHS) and Comprehensive National Nutrition Survey (CNNS), was used for this study. First, we addressed the robustness of MANUSH method of composite indexing over conventional aggregation methods. Second, using MANUSH scores, we assessed the triple burden of malnutrition at the subnational level over different periods NHFS- 3(2005–06), NFHS-4 (2015–16) and CNNS (2106–18). Using mapping and spatial analysis tools, we assessed neighbourhood dependency and formation of clusters, within and across states.ResultMANUSH method scores over other aggregation measures that use linear aggregation or geometric mean. It does so by fulfilling additional conditions of Shortfall and Hiatus Sensitivity, implicitly penalising cases where the improvement in worst-off dimension is lesser than the improvement in best-off dimension, or where, even with an overall improvement in the composite index, the gap between different dimensions does not reduce. MANUSH scores helped in revealing the gaps in the improvement of nutrition outcomes among different indicators and, the rising inequalities within and across states and districts in India. Significant clusters (p < 0.05) of high burden and low burden districts were found, revealing geographical heterogeneities and sharp regional disparities. A MANUSH based index is useful in context-specific planning and prioritising different interventions, an approach advocated by the newly launched National Nutrition Mission in India.ConclusionMANUSH based index emphasises balanced development in nutritional outcomes and is hence relevant for diverse and unevenly developing economy like India.
Osteofibrous dysplasia-like adamantinoma treated via intercalary segmental resection with partial cortex preservation using pedicled vascularized fibula graft: a case report
Authors: Yamamura Yuji , Emori Makoto , Takahashi Nobuyuki , Chiba Mitsumasa , Shimizu Junya , Murahashi Yasutaka , Sugita Shintaro , Iba Kousuke , Hasegawa Tadashi , Yamashita Toshihiko 
Published: August 2020

AbstractBackgroundMorphologically, osteofibrous dysplasia-like adamantinoma is thought to be intermediate between osteofibrous dysplasia and adamantinoma. Its treatment is not well established owing to its rarity.Case presentationWe report about of a 10-year-old girl with osteofibrous dysplasia-like adamantinoma initially diagnosed as osteofibrous dysplasia and treated via intercalary segmental resection with partial cortex preservation using a pedicled vascularized fibula graft for reconstruction. Bone union was observed 9 weeks after surgery. Twenty-two months after the definitive surgery, no recurrence was observed.ConclusionThis case illustrates the upgrade from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma. The surgical method may aid the treatment of osteofibrous dysplasia-like adamantinoma with incomplete cortex involvement of the tumor.
A monocentric, open-label randomized standard-of-care controlled study of XONRID®, a medical device for the prevention and treatment of radiation-induced dermatitis in breast and head and neck cancer patients
Authors: Ingargiola Rossana , De Santis Maria Carmen , Iacovelli Nicola Alessandro , Facchinetti Nadia , Cavallo Anna , Ivaldi Eliana , Dispinzieri Michela , Franceschini Marzia , Giandini Carlotta , Romanello Domenico Attilio , Di Biaso Simona , Sabetti Michela , Locati Laura , Alfieri Salvatore , Bossi Paolo , Guglielmo Mauro , Macchi Fabio , Lozza Laura , Valdagni Riccardo , Fallai Carlo , Pignoli Emanuele , Orlandi Ester 
Published: August 2020

Abstract
Background
This study was an open-label, 2-arms, monocentric, randomized clinical trial comparing Xonrid®, a topical medical device, versus standard of care (SOC) in preventing and treating acute radiation dermatitis (ARD) in Head and Neck Cancer (HNC) and Breast Cancer (BC) patients undergoing radiotherapy (RT).

Methods
Eligible HNC and BC patients were randomized 1:1 to receive Xonrid® + SOC or SOC during RT. Patients were instructed to apply Xonrid® on the irradiated area three times daily, starting on the first day of RT and until 2 weeks after RT completion or until the development of grade ≥ 3 skin toxicity. The primary endpoint was to evaluate the proportion of patients who developed an ARD grade < 2 at the 5th week in both groups. Secondary endpoints were median time to grade 2 (G2) skin toxicity onset; changes in skin erythema and pigmentation and trans-epidermal water loss (TEWL); patient-reported skin symptoms. All patients were evaluated at baseline, weekly during RT and 2 weeks after treatment completion. The evaluation included: clinical toxicity assessment; reflectance spectrometry (RS) and TEWL examination; measurement of patients’ quality of life (QoL) through Skindex-16 questionnaire.

Results
Eighty patients (40 for each cancer site) were enrolled between June 2017 and July 2018. Groups were well balanced for population characteristics. All BC patients underwent 3-Dimensional Conformal RT (3D-CRT) whereas HNC patients underwent Volumetric-Modulated Arc Therapy (VMAT). At week 5 the proportion of BC patients who did not exhibit G2 ARD was higher in Xonrid® + SOC group (p = 0.091). In the same group the onset time of G2 ARD was significantly longer than in SOC-alone group (p < 0.0491). For HNC groups there was a similar trend, but it did not reach statistical significance. For both cancer sites, patients’ QoL, measured by the Skindex-16 score, was always lower in the Xonrid® + SOC group.

Conclusion
Despite the failure to achieve the primary endpoint, this study suggests that Xonrid® may represent a valid medical device in the prevention and treatment of ARD at least in BC patients, delaying time to develop skin toxicity and reducing the proportion of patients who experienced G2 ARD during RT treatment and 2 weeks later.

Trial registration
The study was approved by the Ethical Committee of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT 52/14 - NCT02261181). Registered on ClinicalTrial.gov on 21st August 2017.