bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leveraging Spiking Deep Neural Networks to Understand the Neural Mechanisms Underlying Selective Attention
Authors: Sörensen Lynn K. A. , Zambrano Davide , Slagter Heleen A. , Bohté Sander M. , Scholte H. Steven 
Published: January 2022

Abstract
Spatial attention enhances sensory processing of goal-relevant information and improves perceptual sensitivity. Yet, the specific neural mechanisms underlying the effects of spatial attention on performance are still contested. Here, we examine different attention mechanisms in spiking deep convolutional neural networks. We directly contrast effects of precision (internal noise suppression) and two different gain modulation mechanisms on performance on a visual search task with complex real-world images. Unlike standard artificial neurons, biological neurons have saturating activation functions, permitting implementation of attentional gain as gain on a neuron's input or on its outgoing connection. We show that modulating the connection is most effective in selectively enhancing information processing by redistributing spiking activity and by introducing additional task-relevant information, as shown by representational similarity analyses. Precision only produced minor attentional effects in performance. Our results, which mirror empirical findings, show that it is possible to adjudicate between attention mechanisms using more biologically realistic models and natural stimuli.
Alpha Oscillations Are Involved in Localizing Touch on Handheld Tools
Authors: Fabio Cécile , Salemme Romeo , Koun Eric , Farnè Alessandro , Miller Luke E. 
Published: January 2022

Abstract
The sense of touch is not restricted to the body but can also extend to external objects. When we use a handheld tool to contact an object, we feel the touch on the tool and not in the hand holding the tool. The ability to perceive touch on a tool actually extends along its entire surface, allowing the user to accurately localize where it is touched similarly as they would on their body. Although the neural mechanisms underlying the ability to localize touch on the body have been largely investigated, those allowing to localize touch on a tool are still unknown. We aimed to fill this gap by recording the electroencephalography signal of participants while they localized tactile stimuli on a handheld rod. We focused on oscillatory activity in the alpha (7–14 Hz) and beta (15–30 Hz) ranges, as they have been previously linked to distinct spatial codes used to localize touch on the body. Beta activity reflects the mapping of touch in skin-based coordinates, whereas alpha activity reflects the mapping of touch in external space. We found that alpha activity was solely modulated by the location of tactile stimuli applied on a handheld rod. Source reconstruction suggested that this alpha power modulation was localized in a network of fronto-parietal regions previously implicated in higher-order tactile and spatial processing. These findings are the first to implicate alpha oscillations in tool-extended sensing and suggest an important role for processing touch in external space when localizing touch on a tool.
“Against Muhammad’s Perfidy”: The Jesuit Francisco Combés and His Relación de las islas Filipinas (c.1654)
Authors: Coello de la Rosa Alexandre 
Published: January 2022

Abstract
This article analyzes the centrality of the Jesuit missionaries as indispensable agents in re-establishing negotiations with the Muslims of Mindanao and Sulu. In doing so, I discuss an unpublished Jesuit report: the Relación de las islas Filipinas (Manila, 1654) by the Jesuit Juan Francisco Combés (1620–65), which willfully conflated religious conversion with military intervention and conquest in the interests of securing a permanent base of operations in the southern Philippines. Spanish hegemony in the region was always contested. Therefore, Jesuit superiors strove to convince the civil authorities of Manila, and particularly the governor of the Philippines, don Sabiniano Manrique de Lara (in office 1653–63), to leave definitively the military strongholds in the Moluccas and instead to reinforce the military presidios located in the southern islands of Mindanao as the best way to stop the Muslim raids. Finally, the postscript analyzes the martyrdom of the Jesuits Alejandro López (1604–55) and Juan de Montiel (1632–55) as a propagandistic tool to cement the Jesuit contribution to the Spanish conquest and identify it with Catholic evangelization.
Development of Monoclonal B-cell Lymphocytosis Shortly After Treatment with Nivolumab and Subsequent Progression to Chronic Lymphocytic Leukemia
Authors: Jamali Arsia , Nemovi Khashayar , Kaur Jaspreet , Dasanu Constantin A 
Published: January 2022

Introduction Immune checkpoint inhibitors, such as programmed death (PD)-1 inhibitor nivolumab, are currently widely used in treatment of various malignancies. Due to their widespread application, any new potential adverse effects due to these agents necessitate careful assessment. Case report We report a case of an 81-year-old man with recurrent high-risk malignant melanoma who underwent a 12-month adjuvant treatment with nivolumab. Shortly after the course of nivolumab, he developed monoclonal B-cell lymphocytosis (MBL) which subsequently progressed to chronic lymphocytic leukemia (CLL). Management and outcome The patient is currently doing clinically well in Rai stage 0. Malignant melanoma remains in remission. Conclusion Considering the pathophysiologic plausibility of nivolumab inducing B-cell dysregulation via PD-1 inhibition, we suggest further studies on potential association between nivolumab and B-cell malignancies.
Characteristics and outcomes of patients with blastic plasmacytoid dendritic cell neoplasm treated with frontline HCVAD
Authors: Pemmaraju Naveen , Wilson Nathaniel R. , Garcia-Manero Guillermo , Sasaki Koji , Khoury Joseph D. , Jain Nitin , Borthakur Gautam , Ravandi Farhad , Daver Naval , Kadia Tapan , DiNardo Courtney , Jabbour Elias , Pierce Sherry , Qazilbash Muzaffar , Konopleva Marina , Kantarjian Hagop 
Published: January 2022

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a clinically aggressive blood cancer, often involving the skin, bone marrow, lymph nodes, and central nervous system (CNS) in 20% to 30% of patients. Despite significant progress in CD123- and BCL-2–targeted therapy, most patients are not cured without hematopoietic stem cell transplant (HSCT), and CNS relapses occur quite frequently. Combination approaches with targeted and chemotherapy agents plus incorporation of prophylactic CNS-directed therapy are urgently needed. In this setting, we sought to analyze outcomes using the cytotoxic chemotherapy backbone regimen hyperfractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone (HCVAD). We conducted a retrospective analysis of patients with BPDCN (n = 100), evaluating complete remission (CR) and median overall survival (OS) among 3 groups: those who received frontline HCVAD-based therapy (n = 35), SL-401 (n = 37), or other regimens (n = 28). HCVAD-based regimens yielded higher CR (80% vs 59% vs 43%; P = .01). There was no significant difference in OS (28.3 vs 13.7 vs 22.8 months; P = .41) or remission duration probability among treatment groups (38.6 vs not reached vs 10.2 months; P = .24). HSCT was performed in 51% vs 49% vs 38%, respectively (P = .455). These results suggest a continued important role for HCVAD-based chemotherapy in BPDCN, even in the modern targeted-therapy era, with high CR rates in the frontline setting. Further studies must establish the clinical activity, feasibility, and safety of doublet/triplet combinations of targeted therapies plus cytotoxic agents and the addition of CNS prophylaxis, with the ultimate goal of durable long-term remission for patients with BPDCN.
COVID-19 masquerading as a non-convulsive status epilepticus
Authors: Moorthamers Sofie , Preseau Thierry , Sanoussi Saïd , Gazagnes Marie-Dominique 
Published: January 2022

AbstractSince the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), more and more atypical presentations of COVID-19 are being reported. Here, we present and discuss non-convulsive status epilepticus (NCSE) as presenting symptom of SARS-CoV-2 infection at the Emergency Department.
Intelligent fluorescence image analysis of giant unilamellar vesicles using convolutional neural network
Authors: Lee Il-Hyung , Passaro Sam , Ozturk Selin , Ureña Juan , Wang Weitian 
Published: January 2022

AbstractBackgroundFluorescence image analysis in biochemical science often involves the complex tasks of identifying samples for analysis and calculating the desired information from the intensity traces. Analyzing giant unilamellar vesicles (GUVs) is one of these tasks. Researchers need to identify many vesicles to statistically analyze the degree of molecular interaction or state of molecular organization on the membranes. This analysis is complicated, requiring a careful manual examination by researchers, so automating the analysis can significantly aid in improving its efficiency and reliability.ResultsWe developed a convolutional neural network (CNN) assisted intelligent analysis routine based on the whole 3D z-stack images. The programs identify the vesicles with desired morphology and analyzes the data automatically. The programs can perform protein binding analysis on the membranes or state decision analysis of domain phase separation. We also show that the method can easily be applied to similar problems, such as intensity analysis of phase-separated protein droplets. CNN-based classification approach enables the identification of vesicles even from relatively complex samples. We demonstrate that the proposed artificial intelligence-assisted classification can further enhance the accuracy of the analysis close to the performance of manual examination in vesicle selection and vesicle state determination analysis.ConclusionsWe developed a MATLAB based software capable of efficiently analyzing confocal fluorescence image data of giant unilamellar vesicles. The program can automatically identify GUVs with desired morphology and perform intensity-based calculation and state decision for each vesicle. We expect our method of CNN implementation can be expanded and applied to many similar problems in image data analysis.
Standardization of evaluation method and prognostic significance of histological response to preoperative chemotherapy in high-grade non-round cell soft tissue sarcomas
Authors: Oda Yoshinao , Tanaka Kazuhiro , Hirose Takanori , Hasegawa Tadashi , Hiruta Nobuyuki , Hisaoka Masanori , Yoshimoto Masato , Otsuka Hiroshi , Bekki Hirofumi , Ishii Takeaki , Endo Makoto , Kunisada Toshiyuki , Hiruma Toru , Tsuchiya Hiroyuki , Katagiri Hirohisa , Matsumoto Yoshihiro , Kawai Akira , Nakayama Robert , Kawashima Hiroyuki , Takenaka Satoshi , Emori Makoto , Watanuki Munenori , Yoshida Yukihiro , Okamoto Takeshi , Mizusawa Junki , Fukuda Haruhiko , Ozaki Toshifumi , Iwamoto Yukihide , Nojima Takayuki 
Published: January 2022

Abstract
Background
Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis.

Methods
Using data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board.

Results
A total of 64 patients were eligible for this study. The percentage of viable tumor area ranged from 0.1% to 97.0%, with median value of 35.7%. Regarding concordance proportion between pathologists, the weighted kappa coefficient (κ) score in all patients was 0.71, indicating that the established evaluation method achieved substantial agreement score. When the cut-off value of the percentage of the residual tumor area was set as 25%, the p-value for the difference in overall survival showed the minimum value. Hazard ratio of the non-responder with percentage of the residual tumor < 25%, to the responder was 4.029 (95% confidence interval 0.893–18.188, p = 0.070).

Conclusion
The standardized evaluation method of pathological response to preoperative chemotherapy showed a substantial agreement in the weighted κ score. The evaluation method established here was useful for estimating of the prognosis in STS patients who were administered perioperative chemotherapy with DOX and IFO.

Trial registration
UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).
Anticipating the direction of symptom progression using critical slowing down: a proof-of-concept study
Authors: Schreuder Marieke J. , Wigman Johanna T. W. , Groen Robin N. , Weinans Els , Wichers Marieke , Hartman Catharina A. 
Published: January 2022

Abstract
Background
As complex dynamic systems approach a transition, their dynamics change. This process, called critical slowing down (CSD), may precede transitions in psychopathology as well. This study investigated whether CSD may also indicate the direction of future symptom transitions, i.e., whether they involve an increase or decrease in symptoms.

Methods
In study 1, a patient with a history of major depression monitored their mental states ten times a day for almost eight months. Study 2 used data from the TRAILS TRANS-ID study, where 122 young adults at increased risk of psychopathology (mean age 23.64±0.67 years, 56.6% males) monitored their mental states daily for six consecutive months. Symptom transitions were inferred from semi-structured diagnostic interviews. In both studies, CSD direction was estimated using moving-window principal component analyses.

Results
In study 1, CSD was directed towards an increase in negative mental states. In study 2, the CSD direction matched the direction of symptom shifts in 34 individuals. The accuracy of the indicator was higher in subsets of individuals with larger absolute symptom transitions. The indicator’s accuracy exceeded chance levels in sensitivity analyses (accuracy 22.92% vs. 11.76%, z=-2.04, P=.02) but not in main analyses (accuracy 27.87% vs. 20.63%, z=-1.32, P=.09).

Conclusions
The CSD direction may predict whether upcoming symptom transitions involve remission or worsening. However, this may only hold for specific individuals, namely those with large symptom transitions. Future research is needed to replicate these findings and to delineate for whom CSD reliably forecasts the direction of impending symptom transitions.
Factors affecting spine–femur discordance in the percentage of young adult mean on dual-energy X-ray absorptiometry in the elderly population: a retrospective study
Authors: Akiyama Shoshi , Tanaka Takaaki , Udaka Jun , Inagaki Naoya , Kumagae Yoshio , Chazono Masaaki , Matsuoka Tatsuki , Saito Mitsuru 
Published: January 2022

Abstract
Background
Several retrospective studies have reported spine–femur discordance in bone mineral density (BMD) values. However, the average age of individuals in these studies was the mid-50s, which is younger than the typical age of individuals requiring treatment for primary osteoporosis. Therefore, we aimed to investigate factors associated with discordance in the percentage of young adult mean (YAM) between the lumbar spine and femoral neck in the elderly population.

Methods
We evaluated 4549 dual-energy X-ray absorptiometry (DXA) measurements obtained from 2161 patients (269 men and 1892 women) between January 2014 and December 2017 at our hospital. For individuals with more than one eligible set of measurements, the first record was used. We investigated each patient’s age, sex, body mass index, current smoking status, alcohol consumption, use of steroids, presence of diabetes mellitus, and presence of rheumatoid arthritis.

Results
The mean age of the patients was 76.4 ± 8.9 years. Older age (p <  0.001), male sex (p <  0.001), and diabetes mellitus (p = 0.007) were significantly associated with spine–femur discordance in the percentage of YAM.

Conclusion
The frequency and magnitude of spine–femur discordance in the percentage of YAM from DXA scans increased with age. Notably, more than 77.4% of patients in their 90s had spine–femur discordance > 10% of YAM. Furthermore, the frequency of spine–femur discordance was higher in men and in patients with diabetes mellitus, suggesting that the percentage of YAM at the lumbar spine may not be reliable for diagnosis of osteoporosis in patients with these factors.
A feasibility study of a cognitive behavioral based stress management intervention for nursing students: results, challenges, and implications for research and practice
Authors: Terp Ulrik , Bisholt Birgitta , Hjärthag Fredrik 
Published: January 2022

Abstract
Background
Stress related psychological problems are growing in nursing education and constitute an essential challenge for educators. This makes research about strategies and interventions to meet these problems important. Stress management interventions need to be tested for feasibility and acceptability, before conducting large scale RCTs. The objective of our study was to assess the feasibility and acceptability of a newly developed cognitive behavioral stress management intervention for nursing students.

Methods
Data were collected using a combination of standardized measurements and newly created questionnaires in combination with qualitative data. Our data included recruitment capability, sample characteristics, intervention acceptability and preliminary evaluation of participant psychological changes.

Results
Findings suggested that the feasibility of conducting a full-scale evaluation was confirmed for intervention acceptability, data collection procedures, and adherence. However, difficulties relating to recruitment capability and homework were identified. All aspects taken together, the intervention was found feasible and acceptable to nursing students, and thus a potential stress management intervention for the nurse education context.

Conclusions
Overall, this study provides an insight into the challenges and complexities of developing and evaluating a new brief cognitive behavioral based stress management training intervention in a nurse education setting.
LRG1: an emerging player in disease pathogenesis
Authors: Camilli Carlotta , Hoeh Alexandra E. , De Rossi Giulia , Moss Stephen E. , Greenwood John 
Published: January 2022

AbstractThe secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1) was first described as a key player in pathogenic ocular neovascularization almost a decade ago. Since then, an increasing number of publications have reported the involvement of LRG1 in multiple human conditions including cancer, diabetes, cardiovascular disease, neurological disease, and inflammatory disorders. The purpose of this review is to provide, for the first time, a comprehensive overview of the LRG1 literature considering its role in health and disease. Although LRG1 is constitutively expressed by hepatocytes and neutrophils,Lrg1−/−mice show no overt phenotypic abnormality suggesting that LRG1 is essentially redundant in development and homeostasis. However, emerging data are challenging this view by suggesting a novel role for LRG1 in innate immunity and preservation of tissue integrity. While our understanding of beneficial LRG1 functions in physiology remains limited, a consistent body of evidence shows that, in response to various inflammatory stimuli, LRG1 expression is induced and directly contributes to disease pathogenesis. Its potential role as a biomarker for the diagnosis, prognosis and monitoring of multiple conditions is widely discussed while dissecting the mechanisms underlying LRG1 pathogenic functions. Emphasis is given to the role that LRG1 plays as a vasculopathic factor where it disrupts the cellular interactions normally required for the formation and maintenance of mature vessels, thereby indirectly contributing to the establishment of a highly hypoxic and immunosuppressive microenvironment. In addition, LRG1 has also been reported to affect other cell types (including epithelial, immune, mesenchymal and cancer cells) mostly by modulating the TGFβ signalling pathway in a context-dependent manner. Crucially, animal studies have shown that LRG1 inhibition, through gene deletion or a function-blocking antibody, is sufficient to attenuate disease progression. In view of this, and taking into consideration its role as an upstream modifier of TGFβ signalling, LRG1 is suggested as a potentially important therapeutic target. While further investigations are needed to fill gaps in our current understanding of LRG1 function, the studies reviewed here confirm LRG1 as a pleiotropic and pathogenic signalling molecule providing a strong rationale for its use in the clinic as a biomarker and therapeutic target.
Sonosensitive capsules for brain thrombolysis increase ischemic damage in a stroke model
Authors: Correa-Paz Clara , Navarro Poupard María F. , Polo Ester , Rodríguez-Pérez Manuel , Migliavacca Martina , Iglesias-Rey Ramón , Ouro Alberto , Maqueda Elena , Hervella Pablo , Sobrino Tomás , Castillo José , del Pino Pablo , Pelaz Beatriz , Campos Francisco 
Published: January 2022

Abstract
Background
Ischemic stroke is the most common cerebrovascular disease and is caused by interruption of blood supply to the brain. To date, recombinant tissue plasminogen activator (rtPA) has been the main pharmacological treatment in the acute phase. However, this treatment has some drawbacks, such as a short half-life, low reperfusion rate, risk of hemorrhagic transformations, and neurotoxic effects. To overcome the limitations of rtPA and improve its effectiveness, we recently designed sonosensitive sub-micrometric capsules (SCs) loaded with rtPA with a size of approximately 600 nm, synthesized using the layer-by-layer (LbL) technique, and coated with gelatine for clot targeting. In this study, we evaluated the rtPA release of ultrasound (US)-responsive SCs in healthy mice and the therapeutic effect in a thromboembolic stroke model.

Results
In healthy mice, SCs loaded with rtPA 1 mg/kg responded properly to external US exposure, extending the half-life of the drug in the blood stream more than the group treated with free rtPA solution. The gelatine coating also contributed to stabilizing the encapsulation and maintaining the response to US. When the same particles were administered in the stroke model, these SCs appeared to aggregate in the ischemic brain region, probably generating secondary embolisms and limiting the thrombolytic effect of rtPA. Despite the promising results of these thrombolytic particles, at least under the dose and size conditions used in this study, the administration of these capsules represents a risk factor for stroke.

Conclusions
This is the first study to report the aggregation risk of a drug carrier in neurological pathologies such as stroke. Biocompatibility analysis related to the use of nano-and microparticles should be deeply studied to anticipate the limitations and orientate the design of new nanoparticles for translation to humans.

Graphical Abstract