bluuebunny/crossref_metadata_2025_split huggingface dataset:
Emotion dysregulation, impulsivity and anger rumination in borderline personality disorder: the role of amygdala and insula
Authors: Mitolo M. , D’Adda F. , Evangelisti S. , Pellegrini L. , Gramegna L. L. , Bianchini C. , Talozzi L. , Manners D. N. , Testa C. , Berardi D. , Lodi R. , Menchetti M. , Tonon C. 
Published: April 2023

AbstractBorderline Personality Disorder (BPD) is a severe mental disorder, characterized by deficits in emotion regulation, interpersonal dysfunctions, dissociation and impulsivity. Brain abnormalities have been generally explored; however, the specific contribution of different limbic structures to BPD symptomatology is not described. The aim of this study is to cover this gap, exploring functional and structural alterations of amygdala and insula and to highlight their contribution to neuropsychiatric symptoms. Twenty-eight BPD patients (23.7 ± 3.42 years; 6 M/22F) and twenty-eight matched healthy controls underwent a brain MR protocol (1.5 T, including a 3D T1-weighted sequence and resting-state fMRI) and a complete neuropsychiatric assessment. Volumetry, cortical thickness and functional connectivity of amygdala and insula were evaluated, along with correlations with the neuropsychiatric scales. BPD patients showed a lower cortical thickness of the left insula (p = 0.027) that negatively correlated with the Anger Rumination Scale (p = 0.019; r = − 0.450). A focused analysis on female patients showed a significant reduction of right amygdala volumes in BPD (p = 0.037), that correlate with Difficulties in Emotion Regulation Scale (p = 0.031; r =  − 0.415), Beck Depression Inventory (p = 0.009; r =  − 0.50) and Ruminative Response Scale (p = 0.045; r =  − 0.389). Reduced functional connectivity was found in BPD between amygdala and frontal pole, precuneus and temporal pole. This functional connectivity alterations correlated with Anger Rumination Scale (p = .009; r = − 0.491) and Barratt Impulsiveness Scale (p = 0.020; r = − 0.447). Amygdala and insula are altered in BPD patients, and these two limbic structures are implicated in specific neuropsychiatric symptoms, such as difficulty in emotion regulation, depression, anger and depressive rumination.
NO-mediated dormancy release of Avena fatua caryopses is associated with decrease in abscisic acid sensitivity, content and ABA/GAs ratios
Authors: Kępczyński Jan , Wójcik Agata , Dziurka Michał 
Published: April 2023

Abstract
Main conclusion
NO releases caryopsis dormancy in Avena fatua, the effect being dependent on the level of dormancy. The NO effect involves also the reduction of caryopsis sensitivity to ABA and to a decrease in the ABA to GAs ratio due to a decrease in ABA levels and the lack of effect on GAs levels before germination is completed.

Abstract
Nitric oxide (NO) from various donors (i.e. SNP, GSNO and acidified KNO2), applied to dry caryopses or during initial germination, released primary dormancy in caryopses. Dormancy in caryopses was gradually lost during dry storage (after-ripening) at 25 °C, enabling germination at 20 °C in the dark. The after-ripening effect is associated with a decrease in NO required for germination. In addition, NO decreased the sensitivity of dormant caryopses to exogenous abscisic acid (ABA) and decreased the embryos’ ABA content before germination was completed. However, NO did not affect the content of bioactive gibberellins (GAs) from non-13-hydroxylation (GA4, GA7) and 13-hydroxylation (GA1, GA3, GA6.) pathways. Paclobutrazol (PAC), commonly regarded as a GAs biosynthesis inhibitor, counteracted the dormancy-releasing effect of NO and did not affect the GAs level; however, it increased the ABA content in embryos before germination was completed. Ascorbic acid, sodium benzoate and tiron, scavengers of reactive oxygen species (ROS), reduced the stimulatory effect of NO on caryopsis germination. This work provides new insight on the participation of NO in releasing A. fatua caryopses dormancy and on the relationship of NO with endogenous ABA and GAs.
Characterization and digital spatial deconvolution of the immune microenvironment of intraductal oncocytic papillary neoplasms (IOPN) of the pancreas
Authors: Pea Antonio , Paolino Gaetano , Martelli Filippo , Bariani Elena , Piccoli Paola , Sereni Elisabetta , Salvia Roberto , Lawlor Rita T. , Cheng Liang , Chang David , Scarpa Aldo , Luchini Claudio 
Published: April 2023

AbstractIntraductal oncocytic papillary neoplasm (IOPN) of the pancreas is a distinct entity from intraductal papillary mucinous neoplasms (IPMNs) and is considered one of the precursor lesions of pancreatic cancer. Through immunohistochemistry (IHC) and an artificial intelligence (AI)-based approach, this study aims at characterizing its immune microenvironment. Whole-slide IHC was performed on a cohort of 15 IOPNs, 2 of which harboring an associated adenocarcinoma. The following markers were tested: CD3, CD4, CD8, CD20, CD68, CD163, PD-1, PD-L1, MLH1, PMS2, MSH2, and MSH6. The main findings can be summarized as follows: (i) CD8+ T lymphocytes were the predominant immune cells (p < 0.01); (ii) the vast majority of macrophages were concurrently CD68+ and CD163+; (iii) all tumors showed an activated PD-1/PD-L1 axis, but none had mismatch repair deficiency; (iv) AI-based analysis revealed the presence of 2 distinct regions in each case, namely, Re1, localized at the center of the tumor, and Re2, located at tumor periphery; (v) the infiltrating component of the 2 invasive IOPNs showed a smaller extent of Re1 and a reduced rate of CD4+ cells, as well as a larger extent of Re2 and increased rate of CD8+ cells. IOPNs are lesions enriched in immune cells, with a predominance of CD8+ T lymphocytes and class 2 macrophages. Differently from IPMN-oncogenesis, the progression towards invasive carcinoma is accompanied by an increased rate of CD8+ lymphocytes. This finding may suggest the presence of an active self-immune surveillance in invasive IOPNs, potentially explaining, at least in part, the excellent survival rate of IOPN patients.
Hypofibrinolysis in pediatric patients with veno-occlusive disease in hematopoietic stem cell transplantation
Authors: Schneider Veronika , Cabanillas Stanchi Karin M. , Althaus Karina , Schober Sarah , Michaelis Sebastian , Seitz Christian , Lang Peter , Handgretinger Rupert , Bakchoul Tamam , Hammer Stefanie , Döring Michaela 
Published: April 2023

Abstract
Purpose
Veno-occlusive disease (VOD) is a serious complication of hematopoietic stem cell transplantation (HSCT) with a high incidence in pediatric patients. This study aimed to detect signs of hypofibrinolysis using thrombelastography.

Methods
In this prospective single-center study, thrombelastographic measurements (EX and TPA tests) were taken during HSCT to detect signs of impaired coagulation, clot formation, or hypofibrinolysis.

Results
Of 51 patients undergoing allogeneic and autologous HSCT, five (9.8%) developed VOD and received defibrotide treatment. Thrombelastography measurements were also obtained from 55 healthy children as a control group. The results show that clot lysis was prolonged in VOD patients compared to other HSCT patients and control group (lysis time, TPA test: day + 14 to + 21: VOD: 330 ± 67 s vs. HSCT: 246 ± 53 s; p = 0.0106; control: 234 ± 50 s; control vs. VOD: p = 0.0299). The maximum lysis was reduced in HSCT patients compared to controls (EX test: control: 8.3 ± 3.2%; HSCT: day 0 to + 6: 5.3 ± 2.6%, p < 0.0001; day + 7 to + 13: 3.9 ± 2.1%, p < 0.0001; day + 14 to d + 21: 4.1 ± 2.3%, p < 0.0001).

Conclusion
These results suggest that HSCT patients exhibit reduced fibrinolytic capacities and patients diagnosed with VOD show signs of hypofibrinolysis. This prospective study shows that fibrinolysis can be assessed in a rapid and accessible way via thrombelastography. Thrombelastography might be a parameter to support the diagnosis of a VOD and to serve as a follow-up parameter after the diagnosis of a VOD.
The exocyst complex in neurological disorders
Authors: Halim Dilara O. , Munson Mary , Gao Fen-Biao 
Published: April 2023

AbstractExocytosis is the process by which secretory vesicles fuse with the plasma membrane to deliver materials to the cell surface or to release cargoes to the extracellular space. The exocyst—an evolutionarily conserved octameric protein complex—mediates spatiotemporal control of SNARE complex assembly for vesicle fusion and tethering the secretory vesicles to the plasma membrane. The exocyst participates in diverse cellular functions, including protein trafficking to the plasma membrane, membrane extension, cell polarity, neurite outgrowth, ciliogenesis, cytokinesis, cell migration, autophagy, host defense, and tumorigenesis. Exocyst subunits are essential for cell viability; and mutations or variants in several exocyst subunits have been implicated in human diseases, mostly neurodevelopmental disorders and ciliopathies. These conditions often share common features such as developmental delay, intellectual disability, and brain abnormalities. In this review, we summarize the mutations and variants in exocyst subunits that have been linked to disease and discuss the implications of exocyst dysfunction in other disorders.
Assessing variants of uncertain significance implicated in hearing loss using a comprehensive deafness proteome
Authors: Tollefson Mallory R. , Gogal Rose A. , Weaver A. Monique , Schaefer Amanda M. , Marini Robert J. , Azaiez Hela , Kolbe Diana L. , Wang Donghong , Weaver Amy E. , Casavant Thomas L. , Braun Terry A. , Smith Richard J. H. , Schnieders Michael J. 
Published: April 2023

Abstract
Hearing loss is the leading sensory deficit, affecting ~ 5% of the population. It exhibits remarkable heterogeneity across 223 genes with 6328 pathogenic missense variants, making deafness-specific expertise a prerequisite for ascribing phenotypic consequences to genetic variants. Deafness-implicated variants are curated in the Deafness Variation Database (DVD) after classification by a genetic hearing loss expert panel and thorough informatics pipeline. However, seventy percent of the 128,167 missense variants in the DVD are “variants of uncertain significance” (VUS) due to insufficient evidence for classification. Here, we use the deep learning protein prediction algorithm, AlphaFold2, to curate structures for all DVD genes. We refine these structures with global optimization and the AMOEBA force field and use DDGun3D to predict folding free energy differences (∆∆GFold) for all DVD missense variants. We find that 5772 VUSs have a large, destabilizing ∆∆GFold that is consistent with pathogenic variants. When also filtered for CADD scores (> 25.7), we determine 3456 VUSs are likely pathogenic at a probability of 99.0%. Of the 224 genes in the DVD, 166 genes (74%) exhibit one or more missense variants predicted to cause a pathogenic change in protein folding stability. The VUSs prioritized here affect 119 patients (~ 3% of cases) sequenced by the OtoSCOPE targeted panel. Approximately half of these patients previously received an inconclusive report, and reclassification of these VUSs as pathogenic provides a new genetic diagnosis for six patients.
AI apology: interactive multi-objective reinforcement learning for human-aligned AI
Authors: Harland Hadassah , Dazeley Richard , Nakisa Bahareh , Cruz Francisco , Vamplew Peter 
Published: April 2023

AbstractFor an Artificially Intelligent (AI) system to maintain alignment between human desires and its behaviour, it is important that the AI account for human preferences. This paper proposes and empirically evaluates the first approach to aligning agent behaviour to human preference via an apologetic framework. In practice, an apology may consist of an acknowledgement, an explanation and an intention for the improvement of future behaviour. We propose that such an apology, provided in response to recognition of undesirable behaviour, is one way in which an AI agent may both be transparent and trustworthy to a human user. Furthermore, that behavioural adaptation as part of apology is a viable approach to correct against undesirable behaviours. The Act-Assess-Apologise framework potentially could address both the practical and social needs of a human user, to recognise and make reparations against prior undesirable behaviour and adjust for the future. Applied to a dual-auxiliary impact minimisation problem, the apologetic agent had a near perfect determination and apology provision accuracy in several non-trivial configurations. The agent subsequently demonstrated behaviour alignment with success that included up to complete avoidance of the impacts described by these objectives in some scenarios.
Impact of material combinations and removal and insertion cycles on the retention force of telescopic systems
Authors: Micovic Soldatovic Danka , Bitter Maximiliane , Meinen John , Huth Karin Christine , Liebermann Anja , Stawarczyk Bogna 
Published: April 2023

Abstract
Objectives
A variety of dental materials are available for the fabrication of telescopic crowns. The aim was to investigate the impact of material combinations and removal and insertion cycles on their retention forces.

Materials and methods
CAD/CAM-fabricated cobalt–chromium–molybdenum (CoCr) and zirconia (ZrO2) primary crowns were combined with polyetheretherketone (PEEK), polyetherketoneketone (PEKK), CoCr, and ZrO2 secondary crowns (four combinations included PEEK/PEKK secondary crowns in a thickness of 0.5 mm bonded to the CoCr tertiary construction), resulting in 12 different material combinations: CoCr–PEEK; CoCr–PEKK; CoCr–ZrO2; CoCr–CoCr; CoCr–PEEK 0.5; CoCr–PEKK 0.5; ZrO2–PEEK; ZrO2–PEKK; ZrO2–ZrO2, ZrO2–CoCr; ZrO2–PEEK 0.5; and ZrO2–PEKK 0.5 (n = 15 pairings per material combination). Pull-off tests were performed with a universal testing machine initially and after 500, 5000, and 10,000 removal and insertion cycles in a mastication simulator. Descriptive statistics with the Kolmogorov–Smirnov, Kruskal–Wallis, and Mann–Whitney U tests were computed (α = 0.05).

Results
The tested parameters, material combination, and removal and insertion cycles had significant impact on the retention force values (p < 0.001). An increase in removal and insertion cycles was associated with a decrease in retention forces within CoCr and ZrO2 secondary crowns, regardless of the primary crown material. In contrast, PEEK and PEKK secondary crowns presented higher retention load values after 10,000 cycles than initially.

Conclusion
Different material combinations behaved differently after simulated removal and insertion regimens. This difference should be considered during treatment planning.

Clinical relevance
Telescopic crown systems should be made of materials with predictable retention forces that do not deteriorate with time. The implementation of new materials and technologies facilitates reproducibility and time-saving fabrication.
Lynch syndrome-associated chordoma with high tumor mutational burden and significant response to immune checkpoint inhibitors
Authors: Shinojima Naoki , Ozono Kazutaka , Yamamoto Haruaki , Abe Sakiko , Sasaki Rumi , Tomita Yusuke , Kai Azusa , Mori Ryosuke , Yamamoto Takahiro , Uekawa Ken , Matsui Hirotaka , Nosaka Kisato , Matsuzaki Hiroaki , Komohara Yoshihiro , Mikami Yoshiki , Mukasa Akitake 
Published: April 2023

AbstractChordoma is a rare malignant bone tumor arising from notochordal tissue. Conventional treatments, such as radical resection and high-dose irradiation, frequently fail to control the tumor, resulting in recurrence and re-growth. In this study, genetic analysis of the tumor in a 72-year-old male patient with refractory conventional chordoma of the skull base revealed a high tumor mutational burden (TMB) and mutations in the MSH6 and MLH1 genes, which are found in Lynch syndrome. The patient and his family had a dense cancer history, and subsequent germline genetic testing revealed Lynch syndrome. This is the first report of a chordoma that has been genetically proven to be Lynch syndrome. Chordomas usually have low TMB; however, this is an unusual case, because the TMB was high, and immune checkpoint inhibitors effectively controlled the tumor. This case provides a basis for determining the indications for immunotherapy of chordoma based on the genetic analysis. Therefore, further extensive genetic analysis in the future will help to stratify the treatment of chordoma.
Rockfall susceptibility along Pasang Lhamu and Galchhi-Rasuwagadhi highways, Rasuwa, Central Nepal
Authors: Pokharel Badal , Lim Samsung , Bhattarai Tara Nidhi , Alvioli Massimiliano 
Published: April 2023

AbstractThe road network in Central Nepal suffered blockades and damage from numerous landslides and rockfalls due to the earthquake sequence in Gorkha, Nepal, in 2015. Additionally, frequent rainstorms in the area contributed to the recurrence of rockfalls and other types of landslides, hindering road infrastructure development and environmental management. Despite the several existing regional and local studies on landslide susceptibility in the area, rockfall-specific analysis is still lacking. In this paper, we assessed rockfall susceptibility in the sections of the Pasang Lhamu highway and the Galchhi-Rasuwagadhi highway in the Rasuwa district using a physically based model. We generated three-dimensional rockfall trajectories along the roads and used them to infer the rockfall susceptibility of the area. We selected potential locations for the initiation of rockfalls based on the optimization of the gridded slope angle, relief, and terrain ruggedness, validated the source map using statistical parameters, and compared them with a field-mapped rockfall source inventory. As a result, we identified which road sections in Ramche, Dandagaun, and Syaprubesi are highly susceptible to rockfalls. We published the field-based inventory of rockfall sources and segment-wise rockfall susceptibility of highways, where a rockfall susceptibility index of 5 indicated very high susceptibility and 1 very low susceptibility. Such findings and maps are helpful for researchers, land planners, developers, government bodies working on disaster risk reduction, and policymakers to design a preliminary framework for rockfall mitigation and sustainable roads.
Behavioral scales variability in patients with prolonged disorders of consciousness
Authors: Cortese Maria Daniela , Vatrano Martina , Arcuri Francesco , Raso Maria Girolama , Tonin Paolo , Calabrò Rocco Salvatore , Riganello Francesco 
Published: April 2023

Abstract
Background
The principal conditions differentiating disorders of consciousness (DOC) patients are the unresponsive wakefulness syndrome/vegetative state (UWS/VS) and the minimally conscious state (MCS). Many individuals who suffer from sudden-onset severe brain injury move through stages of UWS/VS and MCS before regaining full awareness. In some patients, the DOC condition is protracted for years (PDOC). In this study, we observed PDOC patients for 6 months to assess possible changes in their level of consciousness.

Methods
We enrolled 40 PDOC patients, 23 UWS/VS and 17 MCS hosted in a dedicated unit for long-term brain injury care. The time from injury was 472 ± 533 days for UWS/VS and 1090 ± 1079 days for MCS. The Wessex Head Injury Matrix (WHIM), Coma Recovery Scale-R (CRS-R), and Nociception Coma Scale were administered monthly for 6 months.

Results
During the period of assessment, the percentage of UWS/VS shifted from 58 to 45%, while for the MCS, from 42 to 55%. A positive correlation was found for the UWS/VS patients between the months of observation with the CRS-R total score and WHIM total numbers of behaviors (TNB). In the UWS/VS group, the CRS-R auditive and visual subscales correlated positively with the observation time. During the whole period of observation, 8 patients had constant CRS-R total scores while the WHIM TNB changed in 7 of them.

Conclusion
Our findings demonstrated that the monthly assessment of PDOC by means of the CRS-R and WHIM was able to detect also subtle changes in consciousness level.
Transcriptomic analysis of lung development in wildtype and CFTR−/− sheep suggests an early inflammatory signature in the CF distal lung
Authors: Kerschner Jenny L. , Paranjapye Alekh , Schacht Makayla , Meckler Frederick , Huang Felix , Bebek Gurkan , Van Wettere Arnaud J. , Regouski Misha , Perisse Iuri Viotti , White Kenneth L. , Polejaeva Irina A. , Leir Shih-Hsing , Harris Ann 
Published: April 2023

AbstractThe precise molecular events initiating human lung disease are often poorly characterized. Investigating prenatal events that may underlie lung disease in later life is challenging in man, but insights from the well-characterized sheep model of lung development are valuable. Here, we determine the transcriptomic signature of lung development in wild-type sheep (WT) and use a sheep model of cystic fibrosis (CF) to characterize disease associated changes in gene expression through the pseudoglandular, canalicular, saccular, and alveolar stages of lung growth and differentiation. Using gene ontology process enrichment analysis of differentially expressed genes at each developmental time point, we define changes in biological processes (BP) in proximal and distal lung from WT or CF animals. We also compare divergent BP in WT and CF animals at each time point. Next, we establish the developmental profile of key genes encoding components of ion transport and innate immunity that are pivotal in CF lung disease and validate transcriptomic data by RT-qPCR. Consistent with the known pro-inflammatory phenotype of the CF lung after birth, we observe upregulation of inflammatory response processes in the CF sheep distal lung during the saccular stage of prenatal development. These data suggest early commencement of therapeutic regimens may be beneficial.
Proctitis in patients with monkeypox infection: a single-center analysis of 42 consecutive cases from a multidisciplinary observational study on monkeypox proctitis
Authors: Guevara-Martínez J. , La-Noire F. Prieto , Arteaga-Asensio P. , Pascual-Miguelañez I. , Moraes Souza R. , Quiles M. , Montes M. , Fondevila C. , Álvarez-Gallego M. ,   Monkeypox multidisciplinary collaboration group, Sendagorta Elena , Gonzalez-Alcolea Natalia , Zapata-Syro Camilo , Maldonado Alfredo , González Claudia Sanz , Marijuan J. L. 
Published: April 2023

Abstract
Background
The current monkeypox (MP) virus outbreak was declared an international emergency in July 2022. The aim of this report is to describe our initial experience with patients with MP, focusing on proctitis.

Methods
We conducted an observational study between 20 May and 31 July 2022, on patients with MP at a reference tertiary center in Madrid, Spain. A descriptive analysis on MP was performed, focusing on its characteristics, symptoms, diagnosis, and outcomes.

Results
A total of 143 positive MP cases were diagnosed in our center; 42 of them [all male, median age 39 years (range: 22–57 years)] had proctitis (29.37%), and 3 patients (2.09%/MP total cases and 7.14%/MP proctitis) required surgical drainage of a perianal abscess.

Conclusions
General and digestive surgeons must be aware of the presence of proctological impairment and complications due to MP virus.