bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of cytotoxic lymphocytes through CD6 enhances killing of cancer cells
Authors: Gurrea-Rubio Mikel , Wu Qi , Amin M. Asif , Tsou Pei-Suen , Campbell Phillip L. , Amarista Camila I. , Ikari Yuzo , Brodie William D. , Mattichak Megan N. , Muraoka Sei , Randon Peggy M. , Lind Matthew E. , Ruth Jeffrey H. , Mao-Draayer Yang , Ding Shengli , Shen Xiling , Cooney Laura A. , Lin Feng , Fox David A. 
Published: January 2024

AbstractImmune checkpoint inhibitors (ICIs) have demonstrated efficacy and improved survival in a growing number of cancers. Despite their success, ICIs are associated with immune-related adverse events that can interfere with their use. Therefore, safer approaches are needed. CD6, expressed by T-lymphocytes and human NK cells, engages in cell–cell interactions by binding to its ligands CD166 (ALCAM) and CD318 (CDCP1). CD6 is a target protein for regulating immune responses and is required for the development of several mouse models of autoimmunity. Interestingly, CD6 is exclusively expressed on immune cells while CD318 is strongly expressed on most cancers. Here we demonstrate that disrupting the CD6-CD318 axis with UMCD6, an anti-CD6 monoclonal antibody, prolongs survival of mice in xenograft mouse models of human breast and prostate cancer, treated with infusions of human lymphocytes. Analysis of tumor-infiltrating immune cells showed that augmentation of lymphocyte cytotoxicity by UMCD6 is due to effects of this antibody on NK, NKT and CD8 + T cells. In particular, tumor-infiltrating cytotoxic lymphocytes from UMCD6-treated mice expressed higher levels of perforin and were found in higher proportions than those from IgG-treated mice. Moreover, RNA-seq analysis of human NK-92 cells treated with UMCD6 revealed that UMCD6 up-regulates the NKG2D-DAP10 receptor complex, important in NK cell activation, as well as its downstream target PI3K. Our results now describe the phenotypic changes that occur on immune cells upon treatment with UMCD6 and further confirm that the CD6-CD318 axis can regulate the activation state of cytotoxic lymphocytes and their positioning within the tumor microenvironment.
Cytokine-induced killer (CIK) cells, successes and challenges: report on the first international conference dedicated to the clinical translation of this unique adoptive cell immunotherapy
Authors: Sharma Amit , Ren Xiubao , Rosato Antonio , Sangiolo Dario , Wang Zibing , Tettamanti Sarah , Zhang Yi , Rettinger Eva , Fenix Kevin Aaron , Sommaggio Roberta , Cappuzzello Elisa , Schmidt-Wolf Ingo G. H. 
Published: January 2024

AbstractOn August 30, 2023, experts from Germany and abroad met to discuss the successes and challenges of cytokine-induced killer cell (CIK) therapy, that recently celebrated its 30th anniversary providing treatment for cancer. This first virtual conference was hosted by CIO Bonn, a certified Comprehensive Cancer Center (CCC) funded by German Cancer Aid (DKH). In addition to keynote speakers involved in CIK cell clinical trials or optimized preclinical models to improve this adoptive cell immunotherapy, more than 100 attendees from around the world also participated in this event. Initiatives to establish the International Society of CIK Cells (ISCC) and a stronger CIK cell network guiding preclinical research and future clinical trials were also announced.
Pharmacokinetics/pharmacodynamics of ivosidenib in advanced IDH1-mutant cholangiocarcinoma: findings from the phase III ClarIDHy study
Authors: Fan Bin , Abou-Alfa Ghassan K. , Zhu Andrew X. , Pandya Shuchi S. , Jia Hongxia , Yin Feng , Gliser Camelia , Hua Zhaowei , Hossain Mohammad , Yang Hua 
Published: January 2024

Abstract
Purpose
Report pharmacokinetic (PK)/pharmacodynamic (PD) findings from the phase III ClarIDHy study and any association between PK/PD parameters and treatment outcomes in this population.

Methods
Patients with mutant isocitrate dehydrogenase 1 (mIDH1) advanced cholangiocarcinoma were randomized at a 2:1 ratio to receive ivosidenib or matched placebo. Crossover from placebo to ivosidenib was permitted at radiographic disease progression. Blood samples for PK/PD analyses, a secondary endpoint, were collected pre-dose and up to 4 h post-dose on day (D) 1 of cycles (C) 1 − 2, pre-dose and 2 h post-dose on D15 of C1 − 2, and pre-dose on D1 from C3 onwards. Plasma ivosidenib and D-2-hydroxyglutarate (2-HG) were measured using liquid chromatography-tandem mass spectrometry. All clinical responses were centrally reviewed previously.

Results
PK/PD analysis was available for samples from 156 ivosidenib-treated patients. Ivosidenib was absorbed rapidly following single and multiple oral doses (time of maximum observed plasma concentration [Tmax] of 2.63 and 2.07 h, respectively). Ivosidenib exposure was higher at C2D1 than after a single dose, with low accumulation. In ivosidenib-treated patients, mean plasma 2-HG concentration was reduced from 1108 ng/mL at baseline to 97.7 ng/mL at C2D1, close to levels previously observed in healthy individuals. An average 2-HG inhibition of 75.0% was observed at steady state. No plasma 2-HG decreases were seen with placebo. Plasma 2-HG reductions were observed in ivosidenib-treated patients irrespective of best overall response (progressive disease, or partial response and stable disease).

Conclusion
Once-daily ivosidenib 500 mg has a favorable PK/PD profile, attesting the 2-HG reduction mechanism of action and, thus, positive outcomes in treated patients with advanced mIDH1 cholangiocarcinoma.

Clinical trial registration
NCT02989857 Registered February 20, 2017.
A spatial measure-valued model for radiation-induced DNA damage kinetics and repair under protracted irradiation condition
Authors: Cordoni Francesco G. 
Published: January 2024

AbstractIn the present work, we develop a general spatial stochastic model to describe the formation and repair of radiation-induced DNA damage. The model is described mathematically as a measure-valued particle-based stochastic system and extends in several directions the model developed in Cordoni et al. (Phys Rev E 103:012412, 2021; Int J Radiat Biol 1–16, 2022a; Radiat Res 197:218–232, 2022b). In this new spatial formulation, radiation-induced DNA damage in the cell nucleus can undergo different pathways to either repair or lead to cell inactivation. The main novelty of the work is to rigorously define a spatial model that considers the pairwise interaction of lesions and continuous protracted irradiation. The former is relevant from a biological point of view as clustered lesions are less likely to be repaired, leading to cell inactivation. The latter instead describes the effects of a continuous radiation field on biological tissue. We prove the existence and uniqueness of a solution to the above stochastic systems, characterizing its probabilistic properties. We further couple the model describing the biological system to a set of reaction–diffusion equations with random discontinuity that model the chemical environment. At last, we study the large system limit of the process. The developed model can be applied to different contexts, with radiotherapy and space radioprotection being the most relevant. Further, the biochemical system derived can play a crucial role in understanding an extremely promising novel radiotherapy treatment modality, named in the community FLASH radiotherapy, whose mechanism is today largely unknown.
Topology optimization of acoustic bandgap crystals for topological insulators
Authors: Li Weibai , Hu Jie , Lu Guoxing , Huang Xiaodong 
Published: January 2024

AbstractRecent advances in topology optimization methods have driven the development of bandgap crystals. These artificial materials with maximized operational bandwidth provide the basis for wave manipulation and investigating the topological phase of matter. However, it is still challenging to efficiently design acoustic bandgap crystals via existing topology optimization methods. Most previous studies considering only a volume fraction constraint on the constituent material may have impractical wide band gaps due to the pseudo-air resonant modes. To solve this issue, this paper establishes a new topology optimization method for creating acoustic bandgap crystals periodically composed of solid and air. We adopt a constraint on air permeability to ensure the connective air channels within the periodic microstructures, which is more applicable in engineering practice. The optimized unit cells from the proposed method are further analyzed to realize topologically protected states, providing opportunities for multi-dimensional wave manipulation in acoustic systems. Numerical examples demonstrate the effectiveness of the proposed method in designing acoustic crystals with broad bandgaps on any given band orders, and gapped/gapless edge states and corner states can be achieved in resulting topological insulators.
Utility of brain imaging in pediatric patients with a suspected accidental spinal injury but no brain injury-related symptoms
Authors: Sirén Aapo , Nyman Mikko , Syvänen Johanna , Mattila Kimmo , Hirvonen Jussi 
Published: January 2024

Abstract
Purpose
Imaging is the gold standard in diagnosing traumatic brain injury, but unnecessary scans should be avoided, especially in children and adolescents. Clinical decision-making rules often help to distinguish the patients who need imaging, but if spinal trauma is suspected, concomitant brain imaging is often conducted. Whether the co-occurrence of brain and spine injuries is high enough to justify head imaging in patients without symptoms suggesting brain injury is unknown.

Objective
This study aims to assess the diagnostic yield of brain MRI in pediatric patients with suspected or confirmed accidental spinal trauma but no potential brain injury symptoms.

Methods
We retrospectively reviewed the medical and imaging data of pediatric patients (under 18 years old) who have undergone concomitant MRI of the brain and spine because of acute spinal trauma in our emergency radiology department over a period of 8 years. We compared the brain MRI findings in patients with and without symptoms suggesting brain injury and contrasted spine and brain MRI findings.

Results
Of 179 patients (mean age 11.7 years, range 0–17), 137 had symptoms or clinical findings suggesting brain injury, and 42 did not. None of the patients without potential brain injury symptoms had traumatic findings in brain MRI. This finding also applied to patients with high-energy trauma (n = 47) and was unrelated to spinal MRI findings.

Conclusion
Pediatric accidental trauma patients with suspected or confirmed spine trauma but no symptoms or clinical findings suggesting brain injury seem not to benefit from brain imaging.
Parasitological and molecular investigation of consequences of raw meat feeding (BARF) in dogs and cats: implications for other pets living nearby
Authors: Tuska-Szalay Barbara , Papdeák Viktória , Vizi Zsuzsanna , Takács Nóra , Hornok Sándor 
Published: January 2024

AbstractConsidering the original nature of carnivorism among dogs and cats, nowadays these pets are increasingly fed BARF (Biologically Appropriate Raw Food/Bone And Raw Food) diet to improve their health conditions. However, this diet may also carry health risks, such as vitamin or mineral deficiencies, and infection with pathogens including parasites. In our study, fecal samples of 89 pet animals kept on BARF diet were subjected to coprological examination followed by molecular analyses. Six of them shed eggs of Dicrocoelium dendriticum. This result was confirmed with PCR and sequencing, and in one case, the DNA of Fasciola hepatica was also demonstrated. In addition, oocysts of Cystoisospora canis, a Cystoisospora ohioensis-like sp. and Eimeria stiedai, as well as sporocysts of a Sarcocystis sp. were also detected. All samples were negative for Neospora caninum and Toxoplasma gondii. In conclusion, no evidence was found for the infection of BARF-fed dogs and cats with parasites that are usually associated with this diet and considered as clinico-pathological risk factors for these pets themselves (e.g., N. caninum, T. gondii). However, fluke eggs (probably originating from ruminants) and oocysts of E. stiedai (from rabbit liver in the food) were demonstrated as pseudoparasites. These species are usually not considered among parasite-associated risks of BARF-feeding, implying that other animals living near BARF-fed pets are neglected in this context. However, where intermediate hosts of D. dendriticum occur in urban areas, BARF-feeding may indirectly affect later other dogs and cats. It was also shown here that BARF-feeding may contribute to the contamination of the environment with E. stiedai oocysts, thus increasing the risks of biliary coccidiosis in nearby living pet rabbits that would otherwise not have access to oocysts of E. stiedai.
Graphical abstract
The interior climate and its microclimatic variation of temperate forests in Northern Patagonia, Argentina
Authors: Simon Alois , Fierke Jonas , Reiter Ernesto J. , Loguercio Gabriel A. , Heinrichs Steffi , Putzenlechner Birgitta , Joelson Natalia Z. , Walentowski Helge 
Published: January 2024

AbstractKnowledge on mesoclimatic zonation and microclimatic variations within mountain forest ecosystems is crucial for understanding regional species turnover and effects of climate change on these systems. The temperate mountain forests in the Andean region of South America are among the largest and contiguous natural deciduous forest areas in the world. Due to their pronounced disturbance regime and different successional stages, a climatic zonation combined with the characterisation of its microclimatic variation is important to identify thresholds of species occurrences.We used micro-loggers to measure air temperature and relative humidity for one year at 40 measurement locations along longitudinal and elevation gradients in mountain forests in Northern Patagonia, Argentina. Our results unveil mesoclimatic patterns within these forests characterised by variations in temperature and vapour pressure deficit along the elevational gradient in general, but also at different times of the year. For example,Austrocedrus chilensisandNothofagus dombeyiforests differed mainly by temperature and its diurnal range in the warmest months of the year. Also, differences between forest stands and gaps were more pronounced in the warmest months of the year and at lower elevations, with up to 2.5 K higher temperatures in the second half of the day in gaps. We found clear indications that shrubland ofNothofagus antarcticarepresenting a successional stage after disturbances alters the mesoclimatic pattern, favouring forest fire ignition. Such mesoclimatic variations have a major influence on tree species turnover and ecological processes within these forest ecosystems.The findings contribute to our understanding of the complex interplay between topography, climate, and vegetation in shaping the spatial patterns of species occurrences.
Home-based high tone therapy may alleviate chemotherapy-induced neuropathic symptoms in patients with colorectal cancer: A randomized double-blind placebo-controlled pilot evaluation
Authors: Wakolbinger-Habel Robert , Reinweber Matthias , Alakraa Mahmoud , Riener Ingrid , Scheffold Brigitte Elisabeth , Racz Krisztina , Selimi Flonza , Straub Claudia , Jauker Jakob , Bily Walter , Niedersüß-Beke Dora , Mayrhofer Karl , Paternostro-Sluga Tatjana 
Published: January 2024

Abstract
Background
Most oncologic patients receiving chemotherapy suffer from neuropathy, which not only severely affects quality of life but also may lead to chemotherapy dose reductions or even discontinuation of cancer therapy. Still, it is difficult to sufficiently control these symptoms with the currently available pharmacological treatments. High tone therapy was reported to be an effective option for neuropathies due to different etiologies. However, to date, there are no studies on high tone therapy in patients with chemotherapy-induced peripheral neuropathy.

Methods
This randomized, double-blind, and placebo-controlled two-center study was conducted at the Departments of Physical and Rehabilitation Medicine at the Clinics Donaustadt and Ottakring, Vienna, Austria. Patients with histologically verified colorectal carcinoma treated with a platin derivate and neuropathic symptoms were invited to participate. High tone therapy took place in a home-based setting using the HiToP 191 PNP ® or placebo device for three weeks. Neuropathic symptoms and quality of life were assessed via questionnaires. After the follow-up examination, an opt-in was offered to the patients in the placebo group in terms of an open-label treatment with a verum HiToP PNP ® device.
In addition, patients with chemotherapy-induced peripheral neuropathy due to various malignant diseases were treated in an open-label setting reflecting a clinical application observation. These patients are reported as a separate group.

Results
In the verum group, there was a significant reduction of paresthesias and mental stress due to paresthesias from baseline until end of therapy, compared to placebo. These findings were observed in the opt-in subgroup, as well. In the open-label clinical application observation group, intensity and mental stress due to paresthesia, pain, cramps, and intensity of tightness/pressure were significantly lower at the end of therapy, compared to baseline.

Conclusions
Home-based high tone therapy brought about a significant alleviation in paresthesias and mental stress due to paresthesias in the verum but not the placebo group. In the clinical application observation, a significant alleviation in several further neuropathic symptoms was seen.

Trial registration
This study was registered at clinicaltrials.gov (NCT06048471, 03/02/2020).
Anterior approach for a stab wound with penetrating rebar injury causing incomplete cauda equina syndrome in lumbosacral spine lesion: a case report and literature review
Authors: Ko Jong-Hyun , Chong Seong-Woo , Nguyen Vinh-Lac , Ham Dong-Hun 
Published: January 2024

Abstract
Purpose
To report a unique case of incomplete CES following a rebar penetrating injury in perineal region with retro-pulsed fragment, which was treated with anterior approach and discuss suitable surgical approach.

Methods
Incomplete cauda equina syndrome caused by non-missile penetrating injury is extremely rare. A 26-year-old male patient presented incomplete cauda equina syndrome due to a penetrating rebar wound from his perineal region to the lumbosacral spine. Computed tomography demonstrated a bony fragment broken from S1 body compressing into the spinal canal.

Results
By anterior approach, we performed partial corpectomy of L5, decompression by retrieving the bony fragment and L5-S1 interbody fusion. The patient had a significant recovery, and no clinical complication was found after over 2-year follow-up.

Conclusion
It is challenging to determine the optimal strategy of surgical treatment for penetrating spinal injuries with retained foreign bodies, here we suggest an anterior approach situation that has the advantage of being able to effectively perform decompression and prevent iatrogenic damages of thecal sac and nerve rootlets.
Validation of the Italian version of the Parkinson’s Disease- Cognitive Functional Rating Scale
Authors: Garon Michela , Weis Luca , Siquier Antònia , Fiorenzato Eleonora , Pistonesi Francesca , Cianci Valeria , Canesi Margherita , Pesce Francesca , Reali Elisa , Pozzi Beatrice , Isaias Ioannis Ugo , Siri Chiara , Santangelo Gabriella , Cuoco Sofia , Barone Paolo , Kulisevsky Jaime , Antonini Angelo , Biundo Roberta 
Published: January 2024

AbstractA key distinguishing factor between mild cognitive impairment (MCI) and dementia in Parkinson’s disease (PD) lies in the notable decrease in functioning due to cognitive impairment. The Parkinson’s Disease-Cognitive Functional Rating Scale (PD-CRFS) was developed to assess functional limitations caused by cognitive impairment, while reducing the influence of motor impairment. The aim of this multicenter study was to (i) validate the Italian version of the PD-CFRS in PD, (ii) determine optimal cut-off scores for detecting MCI and dementia in PD, (iii) compare its performances with the most established functional assessment tool (IADL). Six hundred and sixty nine PD participants were recruited from 4 Italian Movement Disorders centers (Venice, Milan, Gravedona, and Salerno). They underwent Level-II cognitive evaluation, which resulted in 282 PD-NC, 310 PD-MCI, and 77 PDD. The PD-CFRS’s psychometric and clinimetric properties, applicability, and responsiveness were analyzed. The PD-CFRS showed high acceptability. Floor and ceiling effects were acceptable. It also displayed strong internal consistency (Cronbach’s α = 0.738), and test–retest reliability (ICC = .854). The PD-CFRS demonstrated higher coefficient of variation to detect dysfunction in PD-MCI patients in comparison to the IADL scale (PD-CFRS 96% vs IADL 22.5%). Convergent validity with the IADL was r = − 0.638 and − 0.527 in males and females, respectively. PD-CFRS total score negatively correlated with global cognition (MoCA corrected score r = − 0.61; p < 0.001). A cut-off score > 6.5 identified PDD with a sensitivity of 90% and specificity of 88% (AUC = .959). A cut-off value of > 1 detected PD-MCI with a sensitivity of 68% and specificity of 69% (AUC = .695). The Italian version of the PD-CFRS demonstrated to be an easy, valid and reliable tool that properly captures functional impairment due to cognitive decline in PD. It also proved to be particularly effective in the advanced stages of PD, and would be a useful support for the diagnosis of PD-MCI and PDD.
Understanding the integration of accessibility requirements in the development process of information systems: a systematic literature review
Authors: Teixeira Pedro , Eusébio Celeste , Teixeira Leonor 
Published: January 2024

AbstractPeople with disabilities (PwD) are frequently excluded from certain activities due to the lack of accessible information. In this area, information systems can help PwD by allowing access to a range of information about the accessibility of spaces, facilities, and products. There has been an increase in technologies that promote accessibility, but there are few literature studies which analyse how these technologies were developed to ensure access for all. To address this gap, this study aims to explore the integration of accessibility requirements in the processes of developing information systems. To achieve this aim, a systematic literature review was conducted using the PRISMA reporting guidelines. To conduct the review, a search was carried out for primary studies in four well-established databases—SCOPUS, Web of Science, IEEE, and ACM. A snowball search to find additional studies was also performed. Based on this, 34 papers were obtained to conduct the study. In general, the studies published on this topic are relatively recent, with healthcare and education being the two major areas where accessibility in information systems is most addressed. The integration of accessibility seems to be primarily applied during the requirement assessment and testing phases, involving potential users in the process. The results obtained within this systematic literature review raise awareness about the integration of accessibility for the success of solutions, which are oriented towards the accessible market. Additionally, the different practical and theoretical contributions can help future practitioners and technology developers establish guidelines that promote the integration of accessibility, thus achieving a more accessible and inclusive society.