bluuebunny/crossref_metadata_2025_split huggingface dataset:
The importance of precision medicine in modern molecular oncology
Authors: Wang Yuanli , Zheng Dawu 
Published: May 2021

AbstractWith the rapid development of modern medical technology, information data modeling has been gradually applied to clinical diagnosis and treatment. Precision medicine is an important approach that focuses on individual patients in terms of their own characteristics, genomic information, proteomics and even social environments. Genome‐wide high‐throughput technologies, including DNA‐seq, RNA‐seq, exosome‐seq…, contribute enormous amounts of molecular data to aid in diagnosis and analysis. Here, we review the developmental history of different next‐generation sequencing platforms, introduce their applications in different tumor diagnosis and therapy, and further discuss the remaining challenges in precision medicine.
Where have all the young wolves gone? Traffic and cryptic mortality create a wolf population sink in Denmark and northernmost Germany
Authors: Sunde Peter , Collet Sebastian , Nowak Carsten , Thomsen Philip Francis , Hansen Michael Møller , Schulz Björn , Matzen Jens , Michler Frank‐Uwe , Vedel‐Smith Christina , Olsen Kent 
Published: May 2021

AbstractLarge carnivores are currently recolonizing Europe following legal protection, but increased mortality in landscapes highly impacted by humans may limit further population expansion. We analyzed mortality and disappearance rates of 35 wolves (of which three emigrated, nine died and 14 disappeared by 1 January 2020) by genetic monitoring in the heavily cultivated and densely populated Jutland peninsula (Denmark and Schleswig‐Holstein, Germany). Annual traffic kill rate estimates ranged from 0.37 (95% CI: 0.11–0.85) to 0.78 (0.51–0.96) in the German part, equivalent to 0.08 (0.02–0.29)–0.25 (0.13–0.46) for the entire region, in the absence of any registered Danish roadkills. In Denmark, annual mortality rate estimates ranged from 0.46 (0.29–0.67) to 0.52 (0.35–0.71), predominantly from cryptic mortality. Despite successful reproductions, we conclude the region is a wolf population sink, primarily driven by cryptic mortality, most likely illegal killing. We hypothesize that frequent encounters between wolves and wolf‐averse persecutors in cultivated landscapes may cause unsustainably high mortality rates despite the majority of hunters respecting protection laws.
Effects of water‐based Liuzijue exercise on peak exercise capacity, functional exercise capacity, and quality of life in people with COPD
Authors: Liu Xiaodan , Wu Weibing , Li Ning , Li Peijun , Wang Zhenwei , Shan Chunlei 
Published: May 2021

AbstractObjectivesThis study was conducted to investigate the effect of water‐based Liuzijue exercise on peak exercise capacity, functional exercise capacity, and quality of life in people with COPD.MethodsThe study included 50 participants randomly divided into three groups: a control group (CG = 17), a land‐based Liuzijue exercise group (LG = 17), and a water‐based Liuzijue exercise group (WG = 16). The LG and WG performed Liuzijue exercise in different environments, and the CG had no exercise intervention. All participants received prescribed medical treatment. Liuzijue exercise was performed according to the description of Health Qigong Liuzijue compiled by Chinese Health Qigong Association for 60 minutes, two times per week, for 12 weeks.ResultsAfter intervention, peak oxygen uptake and peak working rate were significantly improved in WG (P = .02). The results of the 6 minutes walking test (6MWT) and 30 seconds sit‐to‐stand test were significantly improved in both WG and LG (P < .05), and significant difference was found between WG and CG in 6MWT (P = .03). The St. George's Respiratory Questionnaire (SGRQ) activity score increased significantly in the CG (P = .03), while all domains of SGRQ significantly decreased in both training groups (P < .01). All SGRQ scores showed a significant difference between LG and CG (P < .05) and, except for the activity score, between WG and CG (P < .05).ConclusionsWater‐based Liuzijue exercise can effectively improve peak exercise capacity, functional exercise capacity, and quality of life in people with COPD, especially with respect to increasing peak VO2 and 6MWD.
Folic acid supplementation rescues valproic acid‐induced developmental neurotoxicity and behavioral alterations in zebrafish embryos
Authors: Muhsen Maram , Youngs Jaclyn , Riu Anne , Gustafsson Jan‐Åke , Kondamadugu Vijay Sai , Garyfalidis Elefterios , Bondesson Maria 
Published: May 2021

AbstractObjectiveFetal exposure to the anticonvulsant drug valproic acid (VPA), used to treat certain types of epilepsy, increases the risk for birth defects, including neural tube defects, as well as learning difficulties and behavioral problems. Here, we investigated neurotoxic effects of VPA exposure using zebrafish as a model organism. The capacity of folic acid (FA) supplementation to rescue the VPA‐induced neuronal and behavioral perturbations was also examined.MethodsZebrafish embryos of different transgenic lines with neuronal green fluorescent protein expression were exposed to increasing concentrations of VPA with or without FA supplementation. Fluorescence microscopy was used to visualize alterations in brain structures and neural progenitor cells, as well as motor neurons and neurite sprouting. A twitching behavioral assay was used to examine the functional consequences of VPA and FA treatment.ResultsIn zebrafish embryos, VPA exposure caused a decrease in the midbrain size, an increase in the midline gap of the hindbrain, and perturbed neurite sprouting of secondary motor neurons, in a concentration‐dependent manner. VPA exposure also decreased the fluorescence intensity of neuronal progenitor cells in early developmental stages, indicating fewer cells. Furthermore, VPA exposure significantly altered embryonic twitching activity, causing hyperactivity in dark and hypoactivity in light. Supplementation of FA rescued the VPA‐induced smaller midbrain size and hindbrain midline gap defects. FA treatment also increased the number of neuronal progenitor cells in VPA‐treated embryos and salvaged neurite sprouting of the secondary motor neurons. FA rescued the VPA‐induced alterations in twitching activity in light but not in dark.SignificanceWe conclude that VPA exposure induces specific neurotoxic perturbations in developing zebrafish embryos, and that FA reversed most of the identified defects. The results demonstrate that zebrafish is a promising model to study VPA‐induced teratogenesis and to screen for countermeasures.
TRAF3 and NBR1 both influence the effect of the disease‐causing CYLD(Arg936X) mutation on NF‐κB activity
Authors: Danis Judit , Kelemen Evelyn , Rajan Neil , Nagy Nikoletta , Széll Márta , Ádám Éva 
Published: May 2021

AbstractRecently described Hungarian and Anglo‐Saxon pedigrees that are affected by CYLD cutaneous syndrome (syn: Brooke‐Spiegler syndrome (BSS)) carry the same disease‐causing mutation (c.2806C>T, p.Arg936X) of the cylindromatosis (CYLD) gene but exhibit striking phenotypic differences. Using whole exome sequencing, missense genetic variants of the TRAF3 and NBR1 genes were identified in the affected family members of the Hungarian pedigree that are not present in the Anglo‐Saxon pedigree. This suggested that the affected proteins (TRAF3 and NBR1) are putative phenotype‐modifying factors. An in vitro experimental system was set up to clarify how wild type and mutant TRAF3 and NBR1 modify the effect of CYLD on the NF‐κB signal transduction pathway. Our study revealed that the combined expression of mutant CYLD(Arg936X) with TRAF3 and NBR1 caused increased NF‐κB activity, regardless of the presence or absence of mutations in TRAF3 and NBR1. We concluded that increased expression levels of these proteins further strengthen the effect of the CYLD(Arg936X) mutation on NF‐κB activity in HEK293 cells and may explain the phenotype‐modifying effect of these genes in CYLD cutaneous syndrome. These results raise the potential that detecting the levels of TRAF3 and NBR1 might help explaining phenotypic differences and prognosis of CCS.
Topical application of an amygdalin analogue reduces inflammation and keratinocyte proliferation in a psoriasis mouse model
Authors: Gago‐López Nuria , Lagunas Arnal Carmen , Perez Juan J. , Wagner Erwin F. 
Published: May 2021

AbstractPsoriasis is a chronic inflammatory skin disease without cure. Systemic and biological therapies are the most effective treatments for patients with severe psoriasis. However, these drugs can cause serious side effects from extended use. Safe and effective topical drugs are needed to decrease psoriatic plaques and reduce the risk of adverse effects. Amygdalin analogues are stable small molecules that showed benefits in psoriasis xenografts to immune‐deficient mice by systemic application. However, whether topical application of these amygdalin analogues could reduce the progression of the psoriatic phenotype in an immune‐competent organism is unknown. Here, we analyse the efficiency of topical application of an amygdalin analogue cream on a well‐established genetic and immune‐competent mouse model of psoriasis. Topical application of an amygdalin analogue cream ameliorates psoriasis‐like disease in mice, reduces epidermal hyperplasia and skin inflammation. Amygdalin analogue treatment leads to reduced expression of local pro‐inflammatory cytokines, but systemic pro‐inflammatory cytokines that are highly expressed in psoriasis patients such as IL‐17A, IL6 or G‐CSF are also decreased. Furthermore, expression of important mediators of psoriasis initiation and epidermal hyperplasia, such as TNFa, S100A9 and TSLP, is decreased in lesional epidermis after amygdalin analogue treatment. In conclusion, we show that amygdalin analogue reduces the proliferative capacity of psoriasis‐like stimulated keratinocytes and their inflammatory response in vivo and in vitro. These results suggest that topical application of amygdalin analogues may represent a safe and effective treatment for psoriasis.
Large potential for crop production adaptation depends on available future varieties
Authors: Zabel Florian , Müller Christoph , Elliott Joshua , Minoli Sara , Jägermeyr Jonas , Schneider Julia M. , Franke James A. , Moyer Elisabeth , Dury Marie , Francois Louis , Folberth Christian , Liu Wenfeng , Pugh Thomas A.M. , Olin Stefan , Rabin Sam S. , Mauser Wolfram , Hank Tobias , Ruane Alex C. , Asseng Senthold 
Published: May 2021

AbstractClimate change affects global agricultural production and threatens food security. Faster phenological development of crops due to climate warming is one of the main drivers for potential future yield reductions. To counter the effect of faster maturity, adapted varieties would require more heat units to regain the previous growing period length. In this study, we investigate the effects of variety adaptation on global caloric production under four different future climate change scenarios for maize, rice, soybean, and wheat. Thereby, we empirically identify areas that could require new varieties and areas where variety adaptation could be achieved by shifting existing varieties into new regions. The study uses an ensemble of seven global gridded crop models and five CMIP6 climate models. We found that 39% (SSP5‐8.5) of global cropland could require new crop varieties to avoid yield loss from climate change by the end of the century. At low levels of warming (SSP1‐2.6), 85% of currently cultivated land can draw from existing varieties to shift within an agro‐ecological zone for adaptation. The assumptions on available varieties for adaptation have major impacts on the effectiveness of variety adaptation, which could more than half in SSP5‐8.5. The results highlight that region‐specific breeding efforts are required to allow for a successful adaptation to climate change.
Island sternocleidomastoid myocutaneous flap for posterior pharyngeal wall defect repair after anterior cervical spine surgery
Authors: Zhang Xinling , Zhao Runlei , Wang Guanhuier , Chen Yujie , Ding Pengbing , Yang Xin , Zhao Zhenmin , Zhang Yuan 
Published: May 2021

AbstractInjuries and tumours of the cervical spine represent therapeutic challenges to the treating surgeon due to the complex anatomical relationships and biomechanical features. The anterior cervical midline (ACM) and anterior cervical retropharyngeal (ACR) approaches are effective and safe surgical approaches for certain cervical spine lesions, such as cervical spine neoplasms, atlantoaxial subluxation, and certain odontoid fractures. Posterior pharyngeal wall defects (PPWDs) is one of the most frequently encountered surgical morbidities after anterior cervical spine surgery (ACSS). However, limited information has been published concerning effective approaches for PPWD reconstruction after ACSS. The manuscript aimed to describe a novel application of the island sternocleidomastoid myocutaneous flap (ISMF) in the management of PPWDs after ACSS, including surgery with the ACM approach and ACR approach. From April 2015 to November 2019, the clinical data of three patients with PPWDs repaired using the ISMF in Peking university third hospital were retrospectively analysed. The observational indexes are as follows: postoperative survival of the flap, wound healing 2 weeks after surgery, eating and pronunciation function 2 months after surgery. The above indexes of these three cases recovered well. Three patients did not have any persistent PPWD after repair with the ISMF and did not require any further surgical procedures related to the cervical spine.
Effect of orthodontic therapy in periodontitis and non‐periodontitis patients: a systematic review with meta‐analysis
Authors: Martin Conchita , Celis Beatriz , Ambrosio Nagore , Bollain Juan , Antonoglou Georgios N. , Figuero Elena 
Published: May 2021

AbstractAimTo answer these PICO questions:#1: In adult patients with malocclusion, what are the effects of orthodontic tooth movement (OTM) on clinical attachment level (CAL) changes in treated periodontitis patients with a healthy but reduced periodontium compared to non‐periodontitis patients?#2: In adult patients with treated periodontitis and malocclusion, which is the efficacy of skeletal anchorage devices compared to conventional systems in terms of orthodontic treatment outcomes?Material and methodsSeven databases were searched until June 2020 looking for randomized, non‐randomized trials and case series. Mean effects (ME) and 95% confidence intervals (CIs) were calculated.ResultsTwenty‐six studies with high risk of bias were included.PICO#1: In 26 patients without periodontitis and in 69 treated periodontitis patients, minimal changes in periodontal outcomes were reported after orthodontic therapy (p > 0.05). A significant CAL gain (mm) (ME = 3.523; 95% CI [2.353; 4.693]; p < 0.001) was observed in 214 patients when periodontal outcomes were retrieved before a combined periodontal and orthodontic therapy.PICO#2: Orthodontic variables were scarcely reported, and objective assessment of the results on orthodontic therapy was missing.ConclusionsBased on a small number of low‐quality studies, in non‐periodontitis and in stable treated periodontitis patients, OTM had no significant impact on periodontal outcomes.
Lentigo maligna: defining margins and predictors of recurrence utilizing clinical, dermoscopic, confocal microscopy and histopathology features
Authors: Star P. , Rawson R.V. , Drummond M. , Lo S. , Scolyer R.A. , Guitera P. 
Published: May 2021

AbstractBackgroundLentigo maligna (LM) is a subtype of melanoma in situ with poorly defined margins and a high recurrence rate. The biological behaviour of LM appears to differ widely between cases, from biologically indolent to biologically active variants, with some patients experiencing multiple recurrences. It is not known whether this is secondary to inadequate margins, field cancerization or the innate biology of the lesion itself.Objectives(a) Describe the margins of LM in detail by analysing LM in three zones, that is centre, edge and surround using reflectance confocal microscopy (RCM) and histopathology; (b) ascertain association of histological distance of LM and atypical melanocytic hyperplasia from the surgical margin with multi‐recurrent (MR) disease and (c) identify features (clinical, dermoscopy, RCM and histopathology) associated with MR LM.Methods(1) Descriptive observational study comparing the centre, edge and surround of LM on histopathology and RCM; (2) retrospective cohort study comparing parameters associated with MR and non‐recurrent (NR) LM.Results30 patients (median follow‐up time 6.2 years) were included. On histopathology, confluent or near confluent lentiginous proliferation, melanocyte density >15 per 0.5 mm and adnexal spread were best for distinguishing surround from edge of LM. On RCM, predominant melanocytes, lentiginous proliferation and pleomorphism distinguished surround from centre/edge. MR patients had a median histological distance of LM from the surgical margin of 2mm (versus NR patients with an average distance of 4mm). MR patients had a greater proportion of more florid features, compared with NR on histopathology at both the centre and the edge but were similar in the surround.ConclusionThese data may help pathologists and confocalists better define margins of LM. More florid features in MR patients, despite a similar background of sun‐damaged skin, suggest the innate biology of the lesion rather than the field of cancerization may explain MR LM.
Evaluation of the environmental sustainability of the inshore great scallop (Pecten maximus) fishery in Galicia
Authors: Cortés Antonio , González‐García Sara , Franco‐Uría Amaya , Moreira Maria Teresa , Feijoo Gumersindo 
Published: May 2021

AbstractGreat scallop (Pecten maximus) is a bivalve species belonging to the Pectinidae family that is deeply linked to the well‐known network of pilgrimages in Spain (The Way of Saint James), becoming a gourmet product of the Galician cuisine. The goal of this study was to fill the gaps that currently exist in a specific inventory dedicated to the capture and processing of great scallop, as well as to assess the environmental burdens derived from this system. The construction of a comprehensive life cycle inventory was one of the fundamental stages, gathering primary information from questionnaires filled out by 14 skippers and the manager of the evisceration plant in the port of Cambados. Diesel consumption of the fishing boats was identified as the major contributor to the environmental burdens. Furthermore, electricity consumption in the evisceration plant also stood out as a determinant element in the environmental profile of the product. The integrated GHG emission/protein content correlation placed the scallop in the quadrant of high‐protein content (the highest of the fisheries), but also high environmental impact (mainly due to the high fuel use intensity and low edible yield). It is important to highlight that to date and according to our knowledge, this is the first study that aims to analyze the environmental impacts of the great scallop fishery.
2010 versus the 2000 consensus criteria in patients with normalised insulin‐like growth factor 1 after transsphenoidal surgery has high predictive values for long‐term recurrence‐free survival in acromegaly
Authors: Shen Ming , Chen Zhengyuan , Shou Xuefei , He Wenqiang , Qiao Nidan , Ma Zengyi , Ye Zhao , Zhang Yichao , Zhang Qilin , Zhou Xiang , Cao Xiaoyun , Zhang Zhaoyun , Ye Hongying , Li Yiming , Zhao Yao , Li Shiqi , He Min , Wang Yongfei 
Published: May 2021

AbstractThe present study investigated the factors associated with recurrence during long‐term follow‐up in acromegaly and compared the recurrence rate between patients in remission with 2010 vs 2000 consensus criteria. We retrospectively recruited 133 adult acromegalic patients who had undergone transsphenoidal surgery (TSS) from January 2013 to December 2014 and assessed their clinical characteristics, surgical outcomes and recurrence. Surgical remission was defined as normalised insulin‐like growth factor 1 (IGF‐1) with nadir growth hormone (GH) during an oral glucose tolerance test (OGTT) < 1 μg/ L no less than 3 months after TSS without adjuvant therapy. Recurrence was defined as persistently reelevated IGF‐1 after surgical remission. Cox regression analysis and Kaplan‐Meier survival analysis were performed to evaluate the factors associated with recurrence. Remission was achieved in 77 cases (57.9%) after TSS alone. Recurrence was seen in five cases (6.5%) at 12, 12, 12, 36 and 54 months, respectively, after surgery. Cox regression analysis showed that a nadir GH < 0.4 μg /L (vs 0.4‐1.0 μg /L) at surgical remission (odds ratio [OR] = 0.106; 95% confidence interval [CI] = 0.017‐0.645; P = 0.015) and Ki‐67 index (OR = 2.636; 95% CI = 1.023‐6.791; P = 0.045) were independent factors influencing recurrence. Kaplan‐Meier survival analysis showed that the median recurrence‐free survival was 36 months (95% CI = 20‐52) for patients with nadir GH 0.4‐1.0 μg /L at surgical remission. The median recurrence‐free survival for patients with nadir GH < 0.4 μg /L at surgical remission was much longer (ie, required further follow‐up to estimate). A failure of GH suppression under 0.4 μg /L during an OGTT in patients with normalised IGF‐1 and a higher Ki‐67 index are independent predictors of recurrence after surgical remission in GH‐secreting pituitary adenomas. Compared to patients with nadir GH < 0.4 μg /L, those with nadir GH 0.4‐1.0 μg /L appear to have a significantly higher risk of recurrence.
Understanding Women’s Cardiovascular Health Using MyStrengths+MyHealth: A Patient‐Generated Data Visualization Study of Strengths, Challenges, and Needs Differences
Authors: Austin Robin R. , Mathiason Michelle A. , Lindquist Ruth A. , McMahon Siobhan K. , Pieczkiewicz David S. , Monsen Karen A. 
Published: May 2021

AbstractPurposeThe purpose of this data visualization study was to identify patterns in patient‐generated health data (PGHD) of women with and without Circulation signs or symptoms. Specific aims were to (a) visualize and interpret relationships among strengths, challenges, and needs of women with and without Circulation signs or symptoms; (b) generate hypotheses based on these patterns; and (c) test hypotheses generated in Aim 2.DesignThe design of this visualization study was retrospective, observational, case controlled, and exploratory.MethodsWe used existing de‐identified PGHD from a mobile health application, MyStrengths+MyHealth (N= 383). From the data, women identified with Circulation signs or symptoms (n= 80) were matched to an equal number of women without Circulation signs or symptoms. Data were analyzed using data visualization techniques and descriptive and inferential statistics.FindingsBased on the patterns, we generated nine hypotheses, of which four were supported. Visualization and interpretation of relationships revealed that women without Circulation signs or symptoms compared to women with Circulation signs or symptoms had more strengths, challenges, and needs—specifically, strengths in connecting; challenges in emotions, vision, and health care; and needs related to info and guidance.ConclusionsThis study suggests that visualization of whole‐person health including strengths, challenges, and needs enabled detection and testing of new health patterns. Some findings were unexpected, and perspectives of the patient would not have been detected without PGHD, which should be valued and sought. Such data may support improved clinical interactions as well as policies for standardization of PGHD as sharable and comparable data across clinical and community settings.Clinical RelevanceStandardization of patient‐generated whole‐person health data enabled clinically relevant research that included the patients’ perspective.