bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Easy-to-Use Approach to Detect CNV From Targeted NGS Data: Identification of a Novel Pathogenic Variant in MO Disease
Authors: Corsini Serena , Pedrini Elena , Patavino Claudio , Gnoli Maria , Lanza Marcella , Sangiorgi Luca 
Published: June 2022

BackgroundDespite the new next-generation sequencing (NGS) molecular approaches implemented the genetic testing in clinical diagnosis, copy number variation (CNV) detection from NGS data remains difficult mainly in the absence of bioinformatics personnel (not always available among laboratory resources) and when using very small gene panels that do not meet commercial software criteria. Furthermore, not all large deletions/duplications can be detected with the Multiplex Ligation-dependent Probe Amplification (MLPA) technique due to both the limitations of the methodology and no kits available for the most of genes.AimWe propose our experience regarding the identification of a novel large deletion in the context of a rare skeletal disease, multiple osteochondromas (MO), using and validating a user-friendly approach based on NGS coverage data, which does not require any dedicated software or specialized personnel.MethodsThe pipeline uses a simple algorithm comparing the normalized coverage of each amplicon with the mean normalized coverage of the same amplicon in a group of “wild-type” samples representing the baseline. It has been validated on 11 samples, previously analyzed by MLPA, and then applied on 20 patients with MO but negative for the presence of pathogenic variants in EXT1 or EXT2 genes. Sensitivity, specificity, and accuracy were evaluated.ResultsAll the 11 known CNVs (exon and multi-exon deletions) have been detected with a sensitivity of 97.5%. A novel EXT2 partial exonic deletion c. (744-122)-?_804+?del —out of the MLPA target regions— has been identified. The variant was confirmed by real-time quantitative Polymerase Chain Reaction (qPCR).ConclusionIn addition to enhancing the variant detection rate in MO molecular diagnosis, this easy-to-use approach for CNV detection can be easily extended to many other diagnostic fields—especially in resource-limited settings or very small gene panels. Notably, it also allows partial-exon deletion detection.
Predictive Value of Clinical and Pathological Characteristics for Metastatic Radioactive Iodine-Refractory Differentiated Thyroid Carcinoma: A 16-year Retrospective Study
Authors: Chai Jinyan , Zhang Ruiguo , Zheng Wei , Zhang Guizhi , Jia Qiang , Tan Jian , Meng Zhaowei , Wang Renfei 
Published: June 2022

PurposeTo assess predictive value of clinical and pathological characteristics for metastatic radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC) in early stage retrospectively.MethodsWe studied 199 metastatic DTC patients who were divided into two groups (TgAb negative and TgAb positive). The stimulated Tg (Sti-Tg) at the first and second radioiodine therapy (RIT) were defined as Sti-Tg1 and Sti-Tg2, the suppressed Tg (Sup-Tg) were designated as Sup-Tg1 and Sup-Tg2, while the TgAb were defined as TgAb1 and TgAb2, respectively. Univariate analysis and Logistic regression were used to investigate the effects of 13 observed factors to predict RAIR-DTC.ResultsIn TgAb negative group, ROC curve analysis showed that cut-off values of age, Sti-Tg2/Sti-Tg1 and Sup-Tg2/Sup-Tg1 to predict RAIR-DTC were 40 years old, 57.0% and 81.0%, respectively. Age, extrathyroid invasion, Sti-Tg2/Sti-Tg1, Sup-Tg2/Sup-Tg1 and BRAF gene mutation were proved to be independent factors predicting RAIR-DTC. In TgAb-positive group, ROC curve analysis showed that cut-off values of age, TgAb1 and TgAb2/TgAb1 to predict RAIR-DTC were 55 years old, 297 IU/ml (14.8 times higher than the upper limit) and 53.6%, respectively.ConclusionsFor TgAb-negative DTC, age over 40, extraglandular invasion, mutated BRAF gene, Sti-Tg decreased less than 43%, and Sup-Tg decreased less than 19% after the first two courses of RIT were independent predictors for RAIR-DTC. For TgAb-positive DTC, age over 55, extraglandular invasion, mutated BRAF gene, distant metastasis before RIT, TgAb level 14.8 times higher than the upper limit, TgAb dropped less than 46.4% after two courses of RIT were influencing factors.
Effects of Dual Symbiotic Interactions Performed by the Exotic Tree Golden Wreath Wattle (Acacia cyanophylla Lindl.) on Soil Fertility in a Costal Sand Dune Ecosystem
Authors: Dounas Hanane , Bourhia Mohammed , Outamamat Elmostapha , Bouskout Mohammed , Nafidi Hiba-Allah , El-Sheikh Mohamed A. , Al-Abbadi Ghanim A. , Ouahmane Lahcen 
Published: June 2022

The present study aims to evaluate the effects of the exotic shrub Acacia cyanophylla Lindl. on soil fertility by studying 1) its ability to modify the soil physicochemical composition, 2) its contribution to the soil mycorrhizal potential and its impact on the richness and diversity of the arbuscular mycorrhizal fungi (AMF) community in the rhizospheric soil (RS), and finally 3) its atmospheric nitrogen fixation potential. The physicochemical analysis of the RS has shown that soil invasion by A. cyanophylla has a beneficial effect on its fertility; this advantage is demonstrated by the increase of the organic matter and the nutrient contents (N, P, K, Na, Ca) in the RS. Furthermore, the roots of this shrub exhibited broad AMF colonization, which confirms its high mycotrophic aspect. Four differentiated morphotypes of mycorrhizal spores were isolated from the RS of A. cyanophylla by use of the wet sieving method. In addition, the most probable number method showed that A. cyanophylla was capable of dramatically increasing the mycorrhizal potential of the soil. Indeed, more than 1,213 infectious propagules per one hundred grams of soil were detected in the RS of A. cyanophylla. Moreover, A. cyanophylla roots showed a significant presence of nodules indicating an active atmospheric nitrogen fixation. Counting revealed the presence of at least 130 nodules in the root fragments contained in 1 kg of soil. In conclusion, the biological invasion of sand dunes by the exotic shrub A. cyanophylla exhibited beneficial effects on the soil’s chemical composition and functioning, the activity of rhizobacteria in fixing atmospheric nitrogen, and phosphate bioavailability under the action of the native AMF community.
Influence of Topographic Relief on Sand Transport in the Near-Surface Layer During Dust Storms in the Taklimakan Desert
Authors: Huo Wen , Yang Fan , Wu Ye , Zhi XieFei , Song MeiQi , Zhou ChengLong , Yang XingHua , MamtiMin Ali , He Qing , Wen Cong , Gao JiaCheng , Meng Lu , Hu Shunqi 
Published: June 2022

Dust storms and dust aerosols seriously affect environmental variation and climate change at regional and global scales. Accordingly, these hazards are the current focus in studies related to Earth science. The near-surface layer is an important link for the upward transmission of dust aerosols. However, the difficulty associated with obtaining real-time observation data from this layer has markedly hindered the progress of related research. In sand source areas, the topographic relief of natural dunes is easily ignored, despite serving as an essential factor affecting wind-driven dust emission, transport, and deposition. In this study, we explored the similarities and differences in horizontal dust flux (Q) between Xiaotang and Tazhong using observation data. In Xiaotang, the variation in the Q value with height was found to fit a power function; however, in Tazhong, the Q value did not show a significant gradient change. Such phenomena are caused by the secondary sand source generated by the undulation of natural dunes. The median particle diameter of the dust lifted from the ground during dust storms was essentially the same between Xiaotang and Tazhong, ranging from 74 to 82 μm in Tazhong and from 53 to 81 μm in Xiaotang. The maximum wind speed in Xiaotang was greater than that in Tazhong, resulting in a larger Q value for each particle size range in Xiaotang. The coarse sediment grain was identified as the main factor controlling the vertical variation trend of Q. Further, fine particles were found to have a minor impact.
The Impact of Timing of Pertussis Vaccination During Pregnancy on Infant Antibody Levels at Birth: A Multi-Country Analysis
Authors: Gomme Justin , Wanlapakorn Nasamon , Ha Hoang Thi Thu , Leuridan Elke , Herzog Sereina Annik , Maertens Kirsten 
Published: June 2022

BackgroundPertussis vaccination during pregnancy is an effective strategy at reducing pertussis-related morbidity and mortality in infancy and is recommended across several countries. However, the optimal timepoint for vaccination in pregnancy to afford maximal protection to newborns is yet to be elucidated. This multi-country analysis aimed to model the impact of timing of vaccination during pregnancy on infant antibody titers at birth.MethodsA multi-country analysis on a cohort of mother-infant pairs (n=698) vaccinated between 19.6-37.1 weeks gestation was conducted. Data taken from four parent studies on pertussis vaccination during pregnancy were modelled using natural cubic splines and linear mixed models to study the association of both gestational age at vaccination and the interval between vaccination and delivery with pertussis-specific cord blood antibody levels after pertussis vaccination during pregnancy.ResultsTerm born infants on average achieve the highest antibody levels at birth if women are vaccinated before 31 weeks’ gestation. When considering both term and preterm deliveries, an interval of at least 7.5 weeks between vaccination and delivery is required to achieve the highest cord blood antibody levels. The models show that vaccinating earlier than these timeframes will also provide the infant with equally high antibody levels at birth.ConclusionsVaccinating in the second and early third trimester results in the highest antibody levels at birth. Vaccinating earlier within this window is needed to provide equal benefits to both term and preterm born infants.
Comparison of Corneal Collagen Cross-Linking and Voriconazole Treatments in Experimental Fungal Keratitis for Aspergillus fumigatus
Authors: Zhao Zhennan , Chen Xueli , Shao Yi , Shao Tingting 
Published: June 2022

AimsTo compare the antifungal efficacy of corneal cross-linking (CXL) and voriconazole in experimental Aspergillus keratitis models.MethodsThirty-nine New Zealand rabbits were divided into three groups: a control group, a voriconazole group (M group), and a voriconazole combined with CXL group (CXL-M group). The ulcer area was measured via slit lamp imaging, the corneal and corneal epithelial thickness, and ulcer depth was measured via anterior segment optical coherence tomography (AS-OCT). The existence time of the hyphae was observed via in vivo confocal microscopy (IVCM), and the cornea was taken for pathological examination after modeling and at the end of the study to determine the hyphae and corneal repair. The observation times were as follows: at successful modeling and at 1, 4, 7, 14, 21, and 28 days after intervention.ResultsIn the CXL-M group, ulcer area and depth decreased continuously from Day 4 to Day 28 after CXL (all P &lt; 0.05). In the CXL-M group, ulcer area and depth were smaller than those in the other two groups from Day 4 to Day 21 after CXL (all P &lt; 0.05, except ulcer area in the CXL-M vs. M group on Day 21). The duration of hyphae in the CXL-M group was significantly shorter than in the other two groups (P = 0.025). On Day 28, in CXL-M group, corneal thickness was thicker than baseline (P &lt; 0.05). Meanwhile, in CXL-M group, corneal and corneal epithelial thickness were significantly thinner than in the other two groups (P &lt; 0.001). The CXL-M group had no complications, such as corneal perforation, at the end of the study.ConclusionsVoriconazole combined with CXL is effective in treating Aspergillus-infected keratitis. Combined therapy could effectively inhibit Aspergillus, accelerate corneal repair, and shorten the course of the disease.
Increased Direct Current-Electroencephalography Shifts During Induction of Anesthesia in Elderly Patients Developing Postoperative Delirium
Authors: Windmann Victoria , Dreier Jens P. , Major Sebastian , Spies Claudia , Lachmann Gunnar , Koch Susanne 
Published: June 2022

BackgroundChanges in the direct current (DC) electroencephalography (EEG), so-called DC shifts, are observed during hypoxia, hypo-/hypercapnia, anesthetic administration, epileptic seizures, and spreading depolarizations. They are associated with altered cerebral ion currents across cell membranes and/or the blood–brain barrier (BBB). Here, we measured DC shifts in clinical practice during hyperventilation (HV) and anesthesia induction, and investigated whether such DC shifts correlate with the occurrence of postoperative delirium (POD) in older patients.MethodsIn this prospective observational study (subproject of the BioCog study, NCT02265263; EA2/092/14), a continuous pre- and perioperative DC-EEG was recorded in patients aged ≥65 years. The preoperative DC-EEG included a 2 min HV with simultaneous measurement of end-tidal CO2. Of the perioperative recordings, DC-EEG segments were chosen from a 30 s period at the start of induction of anesthesia (IOA), loss of consciousness (LOC), and during a stable anesthetic phase 30 min after skin incision (intraOP). The DC shift at Cz was determined in μV/s. All patients were screened twice daily for the first seven postoperative days for the occurrence of POD. DC-EEG shifts were compared in patients with (POD) and without postoperative delirium (noPOD).ResultsFifteen patients were included in this subproject of the BioCog study. DC shifts correlated significantly with concurrent HV, with DC shifts increasing the more end-tidal CO2 decreased (P = 0.001, Spearman’s rho 0.862). During the perioperative DC-EEG, the largest DC shift was observed at LOC during IOA. POD patients (n = 8) presented with significantly larger DC shifts at LOC [POD 31.6 (22.7; 38.9) μV/s vs. noPOD 4.7 (2.2; 12.5) μV/s, P = 0.026].ConclusionDC shifts can be observed during HV and IOA in routine clinical practice. At anesthesia induction, the DC shift was greatest at the time of LOC, with POD patients presenting with significantly stronger DC shifts. This could indicate larger changes in gas tensions, hypotension and impaired cerebral autoregulation or BBB dysfunction in these patients.Clinical Trial Registrationwww.clinicaltrials.gov, identifier NCT02265263.
Endovascular Treatment of Complex Intracranial Aneurysms With LEO+ Stents: The LEO II Cohort Study
Authors: Eker Omer F. , Levrier Olivier , Houdart Emmanuel , Bonja Marianne , Herbreteau Denis , Bonafé Alain , Desal Hubert ,   the LEO+ II Investigators
Published: June 2022

IntroductionStent-assisted coiling is an established treatment option for intracranial aneurysms, particularly, wide neck aneurysms with complex anatomy. The purpose of the present study was to assess the safety and efficacy of LEO+ stents in the treatment of intracranial aneurysms.Materials and MethodsA prospective, observational, multicenter study including 12 centers was performed on patients with ruptured, unruptured, and recanalized intracranial aneurysms treated with LEO+ stents. The primary efficacy endpoint was the rate of complete aneurysmal occlusion at 18 months post-procedure, and the primary safety endpoint was the morbidity and mortality at 18 months post-procedure.ResultsFrom March 2015 to June 2017, 176 patients were enrolled (mean age of 54.8 ± 11.5 years; 65.9% women). The aneurysms were located mainly in the anterior communicating artery (29.2%) and the middle cerebral artery (28.6%). They were mostly saccular (94%), with a mean dome size of 5.3 ± 2.6 mm and a mean aspect ratio of 1.2 ± 1.0. In total, 3% of the aneurysms were treated in the acute phase of rupture. Complete/nearly complete aneurysmal occlusion and major recanalization were observed in 89% (n = 146/164) and 1.8% (n = 3/164) of patients at 18-month follow-up, respectively. The LEO+ related mortality rate was 0.6% (n = 1/170), the morbidity rate was 4.1% (n = 7/170), and these patients were mRS 0–2 at 18 months.ConclusionOur results reflecting the use of LEO+ stents in real-world conditions confirm the efficacy and safety of LEO+ stents in the management of complex intracranial aneurysms.
Disruption of Cerebellar–Cerebral Functional Connectivity in Temporal Lobe Epilepsy and the Connection to Language and Cognitive Functions
Authors: Pang Linlin , Fan Binglin , Chen Zirong , Chen Zexiang , Lv Caitiao , Zheng Jinou 
Published: June 2022

ObjectiveTo investigate the changes in the cerebellar-cerebral language network in temporal lobe epilepsy (TLE) patients from the cerebellar perspective, the research analyzes the changes of language and cognitive network in terms of functional connectivity (FC), as well as their efficiency of the reorganization were evaluated basing on relationship between the network metrics and neuropsychological scale scores.Methods30 TLE patients and 30 healthy controls were recruited. Brain activity was evaluated by voxel-mirrored homotopic connectivity analysis (VMHC). Two groups were analyzed and compared in terms of language FC using the following methods: Seed-to-Voxel analysis, pairwise correlations [region of interest(ROI)-to-ROI] and graph theory. Correlation analysis was performed between network properties and neuropsychological score.ResultsCompared with healthy participants, VMHC values in the Cerebellum Anterior Lobe, Frontal Lobe, Frontal_Sup_R/L, Cingulum_Ant_R/L, and Cingulum_Mid_R/L were decreased in TLE patients. Decreased FC was observed from the Cerebelum_10_R to the left inferior frontal gyrus, from the Cerebelum_6_R to the left Lingual Gyrus, from the Cerebelum_4_5_R to left Lingual Gyrus, left Cuneal Cortex and Precuneous Cortex, from the Cerebelum_3_R to Brain-Stem, and from the Cerebelum_Crus1_L to Cerebelum_6_R in TLE patients. The FC was enhanced between bilateral Cingulum_Mid and angular gyrus and frontoparietal insular cranium, between Frontal_Sup_Med L and left/right superior temporal gyrus (pSTG l/r), while it was decreased between left middle temporal gyrus and pSTG l/r. Compared with controls, the Betweenness Centrality (BC) of the right superior marginal gyrus (SMG), Temporal_Pole_Mid_R and Temporal_Mid_L as well as the Degree Centrality (DC) and Nodal Efficiency (NE) of the right SMG were lower in TLE patients. Further analysis showed that decreased VMHC in bilateral Cerebellum Anterior Lobe was positively correlated with the Boston Naming Test score in TLE patients, but it was negatively correlated with the Verbal Fluency Test score. The NE and DC of SMG_R were both negatively correlated with visual perception score in Montreal Cognitive Assessment.ConclusionOur results suggest that presence of abnormalities in the static functional connectivity and the language and cognitive network of TLE patients. Cerebellum potentially represents an intervention target for delaying or improving language and cognitive deficits in patients with TLE.
Real-Time 2D MR Cine From Beam Eye’s View With Tumor-Volume Projection to Ensure Beam-to-Tumor Conformality for MR-Guided Radiotherapy of Lung Cancer
Authors: Nie Xingyu , Li Guang 
Published: June 2022

PurposeTo minimize computation latency using a predictive strategy to retrieve and project tumor volume onto 2D MR beam eye’s view (BEV) cine from time-resolved four-dimensional magnetic resonance imaging (TR-4DMRI) libraries (inhalation/exhalation) for personalized MR-guided intensity-modulated radiotherapy (IMRT) or volumetric-modulated arc therapy (VMAT).MethodsTwo time-series forecasting algorithms, autoregressive (AR) modeling and deep-learning-based long short-term memory (LSTM), were applied to predict the diaphragm position in the next 2D BEV cine to identify a motion-matched and hysteresis-accounted image to retrieve the tumor volume from the inhalation/exhalation TR-4DMRI libraries. Three 40-s TR-4DMRI (2 Hz, 3 × 80 images) per patient of eight lung cancer patients were used to create patient-specific inhalation/exhalation 4DMRI libraries, extract diaphragmatic waveforms, and interpolate them to f = 4 and 8 Hz to match 2D cine frame rates. Along a (40•f)-timepoint waveform, 30•f training timepoints were moved forward to produce 3×(10•f-1) predictions. The accuracy of position prediction was assessed against the waveform ground truth. The accuracy of tumor volume projections was evaluated using the center-of-mass difference (∆COM) and Dice similarity index against the TR-4DMRI ground truth for both IMRT (six beam angles, 30° interval) and VMAT (240/480 beam angles, 1.5°/0.75° interval, at 4/8 Hz, respectively).ResultsThe accuracy of the first-timepoint prediction is 0.36 ± 0.10 mm (AR) and 0.62 ± 0.21 mm (LSTM) at 4 Hz and 0.06 ± 0.02 mm (AR) and 0.18 ± 0.06 mm (LSTM) at 8 Hz. A 10%–20% random error in prediction-library matching increases the overall uncertainty slightly. For both IMRT and VMAT, the accuracy of projected tumor volume contours on 2D BEV cine is ∆COM = 0.39 ± 0.13 mm and DICE = 0.97 ± 0.02 at 4 Hz and ∆COM = 0.10 ± 0.04 mm and DICE = 1.00 ± 0.00 at 8Hz.ConclusionThis study demonstrates the feasibility of accurately predicting respiratory motion during 2D BEV cine imaging, identifying a motion-matched and hysteresis-accounted tumor volume, and projecting tumor volume contour on 2D BEV cine for real-time assessment of beam-to-tumor conformality, promising for optimal personalized MR-guided radiotherapy.
A Pilot, Prospective, Observational Study to Investigate the Value of NGS in Liquid Biopsies to Predict Tumor Response After Neoadjuvant Chemo-Radiotherapy in Patients With Locally Advanced Rectal Cancer: The LiBReCa Study
Authors: Roesel Raffaello , Epistolio Samantha , Molinari Francesca , Saletti Piercarlo , De Dosso Sara , Valli Mariacarla , Franzetti-Pellanda Alessandra , Deantonio Letizia , Biggiogero Maira , Spina Paolo , Popeskou Sotirios Georgios , Cristaudi Alessandra , Mongelli Francesco , Mazzucchelli Luca , Stefanini Federico Mattia , Frattini Milo , Christoforidis Dimitri 
Published: June 2022

IntroductionCirculating tumor DNA (ctDNA) correlates with the response to therapy in different types of cancer. However, in patients with locally advanced rectal cancer (LARC), little is known about how ctDNA levels change with neoadjuvant chemoradiation (Na-ChRT) and how they correlate with treatment response. This work aimed to explore the value of serial liquid biopsies in monitoring response after Na-ChRT with the hypothesis that this could become a reliable biomarker to identify patients with a complete response, candidates for non-operative management.Materials and MethodsTwenty-five consecutive LARC patients undergoing long-term Na-ChRT therapy were included. Applying next-generation sequencing (NGS), we characterized DNA extracted from formalin-fixed paraffin embedded diagnostic biopsy and resection tissue and plasma ctDNA collected at the following time points: the first and last days of radiotherapy (T0, Tend), at 4 (T4), 7 (T7) weeks after radiotherapy, on the day of surgery (Top), and 3–7 days after surgery (Tpost-op). On the day of surgery, a mesenteric vein sample was also collected (TIMV). The relationship between the ctDNA at those time-points and the tumor regression grade (TRG) of the surgical specimen was statistically explored.ResultsWe found no association between the disappearance of ctDNA mutations in plasma samples and pathological complete response (TRG1) as ctDNA was undetectable in the majority of patients from Tend on. However, we observed that the poor (TRG 4) response to Na-ChRT was significantly associated with a positive liquid biopsy at the Top.ConclusionsctDNA evaluation by NGS technology may identify LARC patients with poor response to Na-ChRT. In contrast, this technique does not seem useful for identifying patients prone to developing a complete response.