bluuebunny/crossref_metadata_2025_split huggingface dataset:
The NExT trial: Protocol for a two-phase randomized controlled trial testing transcranial magnetic stimulation to augment exposure therapy for youth with OCD
Authors: Conelea Christine , Breitenfeldt Claire , Wilens Alixandra , Carpenter Linda , Greenberg Benjamin , Herren Jennifer , Jacob Suma , Lewis Charles , McLaughlin Nicole , Mueller Bryon A. , Nelson Steve , O’Connor Erin , Righi Giulia , Widge Alik S. , Fiecas Mark , Benito Kristen 
Published: December 2024

Abstract
Background
Exposure with Response Prevention (ERP) is a first-line treatment for OCD, but even when combined with first-line medications it is insufficiently effective for approximately half of patients. Compulsivity in OCD is thought to arise from an imbalance of two distinct neural circuits associated with specific subregions of striatum. Targeted modulation of these circuits via key cortical nodes (dorsolateral prefrontal cortex [dlPFC] or presupplementary motor area [pSMA]) has the potential to improve ERP efficacy by decreasing compulsions during therapy.

Methods
The NExT (Neuromodulation + Exposure Therapy) trial is a two-phase, multisite early-stage randomized controlled trial designed to examine whether TMS augmentation of ERP alters activity in dlPFC and/or pSMA-associated circuitry and reduces compulsions during therapy in youth with OCD age 12–21 years. Phase 1 (N = 60) will compare two different active TMS regimens with sham: A. continuous theta burst stimulation (cTBS) to pSMA vs. B. intermittent theta burst stimulation (iTBS) to dlPFC. A priori “Go/No-Go” criteria will inform a decision to proceed to Phase 2 and the choice of TMS regimen. Phase 2 (N = 60) will compare the selected TMS regimen vs. sham in a new sample.

Discussion
This trial is the first to test TMS augmentation of ERP in youth with OCD. Results will inform the potential of TMS to enhance ERP efficacy and enhance knowledge about mechanisms of change.

Trial registration
ClinicalTrials.gov NCT05931913. Registered prospectively on July 5, 2023.
Strategies to improve recruitment in mental health clinical trials: a scoping review (RE-MIND study)
Authors: Iflaifel Mais , Hall Charlotte L. , Green Heidi R. , Willis Andrew , Rennick-Egglestone Stefan , Juszczak Edmund , Townsend Mark , Martin Jennifer , Sprange Kirsty 
Published: December 2024

Abstract
Background
Lower-than-expected recruitment continues to be one of the major causes of trial delays, and trials to improve mental health are no exception. Indeed, recruitment challenges in trials of vulnerable populations, such as those living with mental health illness, can even be exacerbated. To address this, researchers are turning to digital and online recruitment strategies, e.g. web-based approaches and multi-media in order to (1) increase recruitment efficiency (recruit to target and on time) and (2) improve diversity in mental health clinical trials to be more inclusive and reduce health inequity. There is, however, inconclusive evidence on the success of digital and online recruitment strategies in mental health clinical trials. The RE-MIND study comprised a scoping review to assess the impact of using such recruitment strategies in mental health clinical trials to inform a more systematic scoping review.

Methods
A cohort of 191 recently published RCTs and randomised feasibility studies were identified from the NIHR Journals Library and top two mental health journals (based on citation metrics), Lancet Psychiatry and JAMA Psychiatry. Population characteristics including gender, ethnicity and age were summarised for inclusivity using descriptive statistics, and recruitment strategies were compared to examine differences in their success in recruiting to target.

Results
After screening, 97 articles were included for review. The review findings showed no evidence that offline or mixed strategies were superior for achieving recruitment targets in mental health trials. However, there was a suggestion that trials using a mixed recruitment strategy improved inclusivity and tended to recruit closer to the target.

Conclusions
The key finding was that consideration should be given to a mixed methods approach to recruitment not only to enable wider and more diverse participation in mental health trials but also to realize greater efficiency.
Borrelia miyamotoi and Borrelia burgdorferi sensu lato widespread in urban areas of the Czech Republic
Authors: Balážová Alena , Václavík Tomáš , Baláž Vojtech , Široký Pavel 
Published: December 2024

Abstract
Background
Borrelia miyamotoi and Borrelia burgdorferi sensu lato (s.l.) are important zoonotic agents transmitted by Ixodes ricinus ticks, which are widely distributed across Central Europe. Understanding the spatial distribution of these pathogens’ prevalence will help identify areas with increased infection risk and facilitate the implementation of effective preventive measures.

Methods
We analysed 12,955 I. ricinus ticks collected from 142 towns in the Czech Republic between 2016 and 2018. The ticks were pooled into 2591 groups of five and tested using duplex quantitative polymerase chain reaction (qPCR) for the presence of B. burgdorferi s.l. and B. miyamotoi. For each location, we estimated the overall prevalence of both agents using the EpiTools Epidemiological Calculator for pooled samples and calculated the minimum infection rate (MIR). To assess the potential risk of infection, we combined data on the abundance of nymphs and females with pathogen prevalence at each sampled site. Using a geographic information system (GIS), we mapped the MIR and infection risk of both Borrelia species across all 142 sampled locations and employed a geostatistical method (ordinary kriging) to predict MIR values and infection risk as continuous surfaces across the entire country.

Results
We detected B. miyamotoi in 110 localities and B. burgdorferi s.l. in all 142 localities. The estimated prevalence of B. miyamotoi and B. burgdorferi s.l. in the collected ticks was 2.1% (95% confidence interval [CI] 1.8–2.3) and 27.1% (95% CI 26.0–28.3), respectively. For B. miyamotoi, we identified previously unknown, geographically distinct hotspots of MIR up to 8.3%, with MIR slightly higher in females (2.3%) than in males (1.9%) and nymphs (1.8%), though the difference was not statistically significant. In contrast, B. burgdorferi s.l. exhibited ubiquitous presence, with consistently high prevalence nationwide, showing similar MIRs in females (16.2%) and males (16.1%), and slightly lower in nymphs (15.6%). The highest infection risk for B. miyamotoi was 12.4 infected vectors per hour in southeastern Moravia, while the highest risk for B. burgdorferi s.l. reached 78.6 infected vectors per hour in the Bohemian-Moravian Highlands.

Conclusions
Borrelia miyamotoi is widespread, forming distinct high-prevalence areas in certain regions. Borrelia burgdorferi s.l. demonstrates consistently high prevalence across most of the country, except for a few localized areas such as southwestern Czechia. Both pathogens exhibit natural nidality, forming regions with elevated prevalence and infection risk. Long-term time-series data are needed to confirm the spatio-temporal stability of these hotspots.

Graphical Abstract
Hosts and vectors of scrub typhus in Chile: epidemiological study and molecular analyses of Orientia infection in rodents and rodent-associated mites
Authors: Martínez-Valdebenito Constanza , Acosta-Jamett Gerardo , Abello Rayitray , Jiang Ju , Richards Allen L. , Abarca Katia , Weitzel Thomas 
Published: December 2024

AbstractCandidatus Orientia chiloensis causes scrub typhus over a wide geographical range in southern Chile. The life cycle, including vectors and reservoirs of this novel rickettsial pathogen, is incompletely understood. We analyzed rodent tissue and rodent-associated mite samples collected during a field study in six localities on Chiloé Island, where human scrub typhus cases have occurred. Using molecular methods, we detected Orientia DNA in 24.8% of rodents, belonging to five of seven captured species. Orientia-infection rates showed geographical variations, but were not influenced by rodent species, sex, age, and mite infestation. Phylogenetic analysis showed that Orientia sequences from trombiculid mites (Proschoengastia eloisae) were identical to those from scrub typhus patients from the same region. The results suggest that these rodent-associated mites serve as vectors and play an important role in the ecology of scrub typhus in southern Chile. Further studies are required to determine whether Orientia-infected rodents can also serve as reservoir of Orientia in Chile.
Graphical Abstract
Microfluidic chip systems for characterizing glucose-responsive insulin-secreting cells equipped with FailSafe kill-switch
Authors: Izadifar Mohammad , Massumi Mohammad , Prentice Kacey J. , Oussenko Tatiana , Li Biao , Elbaz Judith , Puri Mira , Wheeler Michael B. , Nagy Andras 
Published: December 2024

Abstract
Background
Pluripotent cell-derived islet replacement therapy offers promise for treating Type 1 diabetes (T1D), but concerns about uncontrolled cell proliferation and tumorigenicity present significant safety challenges. To address the safety concern, this study aims to establish a proof-of-concept for a glucose-responsive, insulin-secreting cell line integrated with a built-in FailSafe kill-switch.

Method
We generated β cell-induced progenitor-like cells (βiPLCs) from primary mouse pancreatic β cells through interrupted reprogramming. Then, we transcriptionally linked our FailSafe (FS) kill-switch, HSV-thymidine kinase (TK), to Cdk1 gene using a CRISPR/Cas9 knock-in strategy, resulting in a FailSafe βiPLC line, designated as FSβiPLCs. Subsequently we evaluated and confirmed the functionality of the drug-inducible kill-switch in FSβiPLCs at different ganciclovir (GCV) concentrations using our PDMS-based transcapillary microfluidic system. Finally, we assessed the functionality of FSβiPLCs by characterizing the dynamics of insulin secretion in response to changes in glucose concentration using our microfluidic perfusion glucose-stimulated insulin secretion (GSIS) assay-on- chip.

Results
The βiPLCs exhibited Ins1, Pdx1 and Nkx6.1 expression, and glucose responsive insulin secretion, the essential properties of pancreatic beta cells. The βiPLCs were amenable to genome editing which allowed for the insertion of the kill-switch into the 3’UTR of Cdk1, confirmed by PCR genotyping. Our transcapillary microfluidic system confirmed the functionality of the drug-inducible kill-switch in FSβiPLCs, showing an effective cell ablation of dividing cells from a heterogeneous cell population at different ganciclovir (GCV) concentrations. The Ki67 expression assessment further confirmed that slow- or non-dividing cells in the FSβiPLC population were resistant to GCV. Our perfusion glucose-stimulated insulin secretion (GSIS) assay-on-chip revealed that the resistant non-dividing FSβiPLCs exhibited higher levels of insulin secretion and glucose responsiveness compared to their proliferating counterparts.

Conclusions
This study establishes a proof-of-concept for the integration of a FailSafe kill-switch system into a glucose-responsive, insulin-secreting cell line to address the safety concerns in stem cell-derived cell replacement treatment for T1D. The microfluidic systems provided valuable insights into the functionality and safety of these engineered cells, demonstrating the potential of the kill-switch to reduce the risk of tumorigenicity in pluripotent cell-derived insulin-secreting cells.
Matrix-free human lung organoids derived from induced pluripotent stem cells to model lung injury
Authors: Budeus Bettina , Kroepel Chiara , Stasch Lisa Marie , Klein Diana 
Published: December 2024

Abstract
Background
Organoids, as near-physiological 3D culture systems, offer new opportunities to study the pathogenesis of various organs in mimicking the cellular complexity and functionality of human organs.

Method
Here we used a quite simple and very practicable method to successfully generate induced pluripotent stem cell (iPSC)-derived human lung organoids (LuOrg) in a matrix-free manner as an alternative to the widely used preclinical mouse models in order to investigate normal lung damage in detail and as close as possible to the patient. We performed detailed morphological and molecular analyses, including bulk and single cell RNA sequencing, of generated lung organoids and evaluated the quality and robustness of our model as a potential in vitro platform for lung diseases, namely radiation-induced lung injury.

Results
A matrix-free method for differentiation of iPSCs can be used to obtain lung organoids that morphologically reflect the target tissue of the human lung very well, especially with regard to the cellular composition. The different cellular fates were investigated following the genotoxic stress induced by radiation and revealed further insights in the radiation-sensitivity of the different lung cells. Finally, we provide cellular gene sets found to be induced in the different lung organoid cellular subsets after irradiation, which could be used as additional RT response and particularly senescence gene sets in future studies.

Conclusion
By establishing these free-floating LuOrgs for the investigation of cancer therapeutic approaches as a new and patient-oriented in vitro platform particularly in experimental radiooncology, not only a reduction in the number of experimental animals, but also an adequately and meaningfully replacement of corresponding animal experiments can be achieved.
Serotype diversity of Actinobacillus pleuropneumoniae detected by real-time PCR in clinical and subclinical samples from Spanish pig farms during 2017–2022
Authors: Arnal Bernal José Luis , Gottschalk Marcelo , Lacotoure Sonia , Sanz Tejero Celia , Chacón Pérez Gema , Martín-Jurado Desiree , Fernández Ros Ana Belén 
Published: December 2024

AbstractActinobacillus pleuropneumoniae is the causative agent of porcine pleuropneumonia, a challenging respiratory disease for the global swine industry. Variations in the serotypes associated with clinical disease have been observed in different regions worldwide. This study aimed to provide an updated epidemiological assessment of A. pleuropneumoniae serotypes in Spain, incorporating bacterial characterization through serotyping and toxinotyping. Serotypes 9/11, 2, 4, 5, 17, and 13 were frequently identified in diseased animals. Furthermore, qPCR of lung samples from an outbreak, even when samples were pooled, emerged as a robust diagnostic tool, enabling the rapid detection of A. pleuropneumoniae and their serotypes without the need for microbiological isolation. This technology also facilitates serotype monitoring of apparently healthy herds through the testing of oral fluids. The study revealed the frequent simultaneous presence of diverse serotypes within a farm. Serotypes 1, 7, 10, 12, 18, and 19 were frequently found in subclinically infected animals but were rarely detected in acute pleuropneumonia outbreaks in the current study. These results provide valuable information for interpreting the potential virulence of the different serotypes in Spain. However, other predisposing factors and the immune status of the herds such as type of vaccines used when appropriate, should be carefully considered before drawing definitive conclusions. Nevertheless, the study offers valuable insights that underscore the necessity for detailed regional data to contribute toward a comprehensive understanding of the disease dynamics and toward formulating effective control measures for porcine pleuropneumonia.
A finite element approach to the Keller–Segel Chemotaxis system with impact of nonlocal diffusion
Authors: Baskar A. , Parthiban V. 
Published: December 2024

AbstractThis paper presents the investigation of a boundedness solution for a Keller–Segel chemotaxis (KSC) system with nonlocal diffusion. In order to achieve boundedness, we derive the necessary and sufficient condition based on the assumption of ensuring a unique classical global bounded solution for the proposed KSC system. In this work, the proposed system’s boundedness condition is determined based on three particular situations: when $\chi <\chi ^{*}$
χ
<

χ
∗

, $\chi <\kappa $
χ
<
κ
, and when $\chi =\kappa $
χ
=
κ
. Finally, the effectiveness of the nonlinear and nonlocal diffusion terms in the KSC system is demonstrated through numerical simulations under consideration of the values of system parameters. From the simulation results, we can confirm the effectiveness of the proposed method.
Weapon use during the index offense: a study among forensic psychiatry patients in Ontario, Canada
Authors: Kaggwa Mark Mohan , Davids Arianna , Mohibi Parwiz , Erb Bailea , Bradford John , Chaimowitz Gary Andrew , Olagunju Andrew Toyin 
Published: December 2024

Abstract
Background
Understanding the nature and circumstances around the use of weapons to perpetrate an offense among individuals with mental illness is crucial for evidence-informed policies and actions. However, little is known about the prevalence and factors associated with weapon use during index offenses among patients in the forensic system. Therefore, the present study was designed to address this gap and determine the prevalence and the patient and victim characteristics associated with weapon use during the index offense in a Canadian province.

Methods
This retrospective exploratory study utilized data extracted from the Ontario Review Board reports of 2014/15. Data was analyzed using Stata, and logistic regression was employed to determine the factors associated with weapon use.

Results
Approximately half (48.11%) of the individuals included in this analysis (n = 819) used weapons during their index offense as an instrument of violence. Both patient-related and victim-related factors had a statistically significant association with weapon use during index offenses. Specifically, two patient-related factors (including a history of hospitalization prior to the index offense and diagnosis of personality disorder) were associated with lower odds of weapon use during the index offense. However, only prior hospitalization remained statistically significant after adjusting for victims’ factors. Victim-related factors were associated with both lower and higher odds of weapon use during the index offense. The highest odds of weapon use were found if the victim was an extended family member of the patient, followed by sibling, lover/partner/spouse, parent, and then adult acquaintance. The odds of weapon use during the index offense were lower if victims were healthcare workers, law enforcement professionals, and females when compared to adult strangers.

Conclusion
The study highlights the significant role of both patients’ and victims’ characteristics as important factors associated with weapon use during index offenses among forensic patients. Notably, prior hospitalization emerged as a crucial factor with a reduced likelihood of weapon use. Implicitly, this underscores the importance of risk mitigation strategies.
Paleomagnetic study of the 30 ka Aira caldera-forming eruption and 60–45 ka Iwato pyroclastic flow deposits, southern Kyushu, Japan
Authors: Hasegawa Takeshi , Mochizuki Nobutatsu , Shibuya Hidetoshi , Nishihara Ayumu , Kusu Chie , Shibata Shohei , Okada Makoto , Nishiki Kuniaki , Sato Yuki 
Published: December 2024

AbstractTo constrain the age and duration of large-scale caldera-forming eruptions, we measured paleomagnetic directions of pyroclastic deposits from the 30 ka Aira caldera eruption sequence, and the 60–45 ka Iwato pyroclastic flow deposits around Aira caldera in southern Kyushu, Japan. The 30 ka Aira caldera eruption sequence consists of Osumi pumice fall (OS), Tarumizu pyroclastic flow deposit (TM), Ito ignimbrite (IT) and co-ignimbrite ash (AT), in ascending order. Oriented samples were collected by drilling for OS, TM and welded ignimbrites, and by cubing for non-welded (unconsolidated) pyroclastic flow deposit. We systematically sampled Ito ignimbrite with the degree of welding as: non-welded (IT1), moderately welded (IT2), and strongly welded (IT3) facies that is limitedly distributed in north of Aira caldera. Mean paleomagnetic directions of OS, TM, IT1 and IT2 are consistent with those previously reported for AT and welded facies of IT. Although OS samples were collected from multiple pumice clasts at proximal locations, we obtained well-defined mean paleomagnetic directions corresponding to those of co-eruptive pyroclastic flow (TM). This suggests that even clast-supported and non-welded pumice fall can retain thermoremanent magnetization at the time of deposition. Significance tests for our mean paleomagnetic directions showed that of all sequential units of the Aira caldera-forming eruption deposits, only IT3 has a different paleomagnetic direction. Based on reported paleosecular variation changing rates in Japan, and on the angular difference associated with error of the two paleosecular directions, we estimate the time gap between IT3 and IT2, to be 24.3 ± 16.3 years. A conductive cooling model explains this time difference as due to differences in cooling time between quickly, and slowly cooled parts of a thick single ignimbrite unit. Although the possibility that multiple flow units occurred within tens of years of each other cannot be excluded, there are no observations of clear flow unit boundaries in the Ito ignimbrite to support the suggestion that the Aira caldera-forming eruption sequence was deposited within a shorter time than years. In addition, the age of Iwato pyroclastic flow deposit, which has been situated between 60 and 45 ka, was estimated by calculating the angular distance between the mean paleomagnetic direction and the modeled secular variation curve from the GGF100 ka. As the result, we determine the most probable age to be around 56 ka.
Graphical abstract
Terrestrial-origin O+ ions below 1 keV near the Moon measured with the Kaguya satellite
Authors: Yamauchi D. , Nosé M. , Harada Y. , Yamamoto K. , Keika K. , Nagamatsu A. , Yokota S. , Saito Y. , Glocer A. 
Published: December 2024

AbstractIn this study, we investigated terrestrial-origin O+ ions below 1 keV around the Moon using data from the Kaguya satellite between December 2007 and June 2009. These terrestrial-origin low-energy O+ ions were identified based on three parameters: the periodicity of O+ ion count enhancement corresponding to Kaguya’s 2-h orbital period, the count ratio of O+ ions to Na+ and Al+ ions, and the direction of ion bulk velocity in the Sun–Earth direction. We identified three intervals that included such O+ ions: 14:30–20:30 UT on June 19, 2008, 19:00 UT on July 16, 2008 to 03:00 UT on July 17, 2008, and 14:00–24:00 UT on June 7, 2009. These intervals were found in the dawn sector, the dusk sector, and the midnight to dawn sector within the magnetotail, respectively. We examined the relation between geomagnetic storm conditions and increases in terrestrial-origin O+ ion counts and found that all three intervals occurred during the late recovery phase of moderate/weak magnetic storms. Since moderately/weakly disturbed conditions (Dst = –40 nT to –20 nT) account for approximately 21% of the total time between 1957 and 2016, we suggest that low-energy O+ ions from the Earth have a non-negligible impact on the ion composition and the ion mass density in the lunar plasma environment.
Graphical abstract