bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Clinical Trial of Trametinib and Low-Dose Dabrafenib in Advanced, Previously Treated BRAFV600/NRASQ61 Wild-Type Melanoma (TraMel-WT)
Authors: Awada Gil , Dirven Iris , Schwarze Julia Katharina , Tijtgat Jens , Fasolino Giuseppe , Kockx Mark , Neyns Bart 
Published: February 2024

PURPOSE Patients with BRAF V600/ NRAS Q61 wild-type melanoma who progress after immune checkpoint inhibitors (ICIs) have a poor prognosis. MEK inhibition has shown activity in this patient population but is associated with treatment-limiting skin toxicity. Combining a BRAF inhibitor with a MEK inhibitor is associated with less skin toxicity. METHODS This phase II trial investigated trametinib (2 mg once daily) in patients with advanced BRAF V600/ NRAS Q61 wild-type, ICI-refractory melanoma. In case of treatment-limiting skin toxicity, low-dose dabrafenib (50 mg twice daily) was added to trametinib. After a trial amendment, both drugs were combined up-front. The confirmed objective response rate (cORR) served as the primary end point. RESULTS Twenty-four patients were included (50% male; median age 57 years; 92% Eastern Cooperative Oncology Group Performance Status 0-2; 75% stage IV-M1c/stage IV-M1d; median number of prior therapies: two [range, 1-5]). Three patients were enrolled before and 21 patients after the amendment, respectively. Seven confirmed and one unconfirmed partial responses (PRs) were observed (cORR, 29.2%). The median duration of response was 16.6 weeks (95% CI, 5.5 to 27.7). Stable disease (SD) was the best response in an additional five patients. Among the responding patients, genetic alterations causing mitogen-activated protein kinase (MAPK) pathway activation were documented in six patients. The disease control rate in patients with MAPK pathway–activating alterations was 64.3% (five confirmed PR, one unconfirmed PR, and three SD). The median progression-free survival was 13.3 weeks (95% CI, 3.5 to 23.1), and the median overall survival was 54.3 weeks (95% CI, 37.9 to 70.6). Adding low-dose dabrafenib to trametinib effectively mitigated or prevented treatment-limiting trametinib-related skin toxicity. CONCLUSION The combination of trametinib plus low-dose dabrafenib demonstrated encouraging efficacy and effective mitigation of skin toxicity in patients with advanced, ICI-pretreated BRAF V600/ NRAS Q61 wild-type melanoma patients. MAPK pathway–activating alterations hold promise as a predictive biomarker.
Conventional HDL Subclass Measurements Mask Thyroid Hormone-dependent Remodeling Activity Sites in Hypothyroid Individuals
Authors: Bagdade John D , McCurdy Carrie E 
Published: February 2024

Abstract

Context
Earlier nuclear magnetic resonance spectroscopy (NMR) studies of plasma lipoproteins estimated by size as small, medium, and large particles, demonstrated hypothyroidism was associated with increases in very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and intermediate-density lipoprotein (IDL) subclass particle number but variable changes in the high-density lipoprotein (HDL) subclasses. These disparate changes in HDL might be explained by reduced activity of the thyroid hormone-dependent remodeling proteins whose subclass specificity may be obscured when the 5 HDL subclasses identified by NMR are combined by size.

Objective
This work aimed to determine whether directional changes in particle number of individually measured HDL subclasses correlate with reduced activity of their thyroid hormone–dependent remodeling proteins in hypothyroid individuals.

Methods
VLDL, LDL, IDL, and HDL subclasses were measured by NMR in 13 thyroidectomized individuals 1 month following thyroid hormone withdrawal and 3 months after replacement. Changes in particle numbers in each subclass were compared when expressed individually and by size.

Results
Following thyroid hormone withdrawal, plasma lipids and VLDL, LDL, and IDL subclass particle number increased. HDL particle number nearly doubled in very small HDL-1 (P = .04), declined in small HDL-2 (P = .02), and increased 2-fold in HDL-5 (P = .0009).

Conclusion
The increment in HDL-1 and decline in HDL-2 subclasses is consistent with their precursor-product relationship and reduced lecithin cholesterol acyltransferase activity while the almost 2-fold increase in large HDL-5 is indicative of diminished action of hepatic lipase, phospholipid transfer protein, and endothelial lipase. These findings are inapparent when the 5 subclasses are expressed conventionally by size. This linking of specific HDL subclasses with HDL remodeling protein function provides new details about the specificity of their interactions.
The interaction of in vivo muscle operating lengths and passive stiffness in rat hindlimbs
Authors: Horner Angela M. , Azizi Emanuel , Roberts Thomas J. 
Published: February 2024

ABSTRACT
The operating length of a muscle is a key determinant of its ability to produce force in vivo. Muscles that operate near the peak of their force–length relationship will generate higher forces whereas muscle operating at relatively short length may be safe from sudden lengthening perturbations and subsequent damage. At longer lengths, passive mechanical properties have the potential to contribute to force or constrain operating length with stiffer muscle–tendon units theoretically being restricted to shorter lengths. Connective tissues typically increase in density during aging, thus increasing passive muscle stiffness and potentially limiting the operating lengths of muscle during locomotion. Here, we compare in vivo and in situ muscle strain from the medial gastrocnemius in young (7 months old) and aged (30–32 months old) rats presumed to have varying passive tissue stiffness to test the hypothesis that stiffer muscles operate at shorter lengths relative to their force–length relationship. We measured in vivo muscle operating length during voluntary locomotion on inclines and flat trackways and characterized the muscle force–length relationship of the medial gastrocnemius using fluoromicrometry. Although no age-related results were evident, rats of both age groups demonstrated a clear relationship between passive stiffness and in vivo operating length, such that shorter operating lengths were significantly correlated with greater passive stiffness. Our results suggest that increased passive stiffness may restrict muscles to operating lengths shorter than optimal lengths, potentially limiting force capacity during locomotion.
Citizens’ reflections on an open, distance intergenerational program for online risk prevention
Authors: Torres-Hernández Norma , Gallego-Arrufat María-Jesús , García-Ruiz María del Mar 
Published: February 2024

Online risks are a concern for citizens in the digital society. Many sectors of the population lack training to face, prevent and solve problematic situations arising from Internet use. University researchers and innovation agents in small towns in southern Spain are carrying out an educational programme of 13 intergenerational workshops to strengthen digital competence and citizenship involving 239 participants. The main objective of this article is to describe and interpret shared reflections on various problematic situations related to the use of the Internet and technology. A content analysis of 864 reflections and experiences contained in seven dimensions and 31 categories is carried out. The results show that the participating citizens are characterised by a high awareness of online risks, they tend to seek help and concrete solutions on issues related to data security, excessive use of mobile phones and online scams and frauds. We propose the need for training to develop a fully digital, responsible and tech-savvy citizenship and an integrated digital model of education focused on protecting the well-being and online rights of citizens.
PoT quantization and rotational update mechanism for optimizing equalization in passive optical networks
Authors: Sang Bohan , Wang Yikai , Liu Jiaxuan , Zhang Long , Wang Kaihui , Jiang Luhan , Ge Jingtao , Zhao Li , Zhou Wen , Yu Jianjun 
Published: February 2024

We propose a low-complexity real-time equalization scheme for passive optical networks (PONs), which provides equalization with similar performance and ultra-low digital signal processing (DSP) resource usage compared to traditional schemes in experimental verification. With the help of the proposed scheme, FIR equalizers with multiple taps can be equivalent to equalizers with only two active taps, while other taps are quantified and stored, which can replace complex multiplications with simple shift operations. We introduce powers-of-two (PoT) non-uniform quantization technology to real-time transmission at the physical layer, which helps to save quantization precision and simplify multiplication complexity. We propose the rotational update mechanism (RUM), which solves the problem that the weight value after PoT non-uniform quantization is difficult to update. The proposed scheme with PoT and RUM greatly reduces the required hardware resources and power consumption, and the optical modules can use existing resources to support the additional number of taps required for higher baud rates. We verified the proposed scheme in decision-directed least mean square (DDLMS) equalization. The improved equalization scheme is implemented in the XCVU9P-FLGB2104-2-I Xilinx FPGA with a clock frequency of 230.4 MHz. The results show that the proposed equalization scheme can reduce up to 99.5% DSP resource usage compared to a normal DDLMS equalizer with 15 taps. We successfully realized 29.4912 Gbit/s PAM4 real-time IM/DD transmission over 25-km SSMF with a BER below the KP4 threshold utilizing the proposed DDLMS with PoT and RUM. The innovation of this paper lies in two aspects: (1) the introduction of the PoT quantization method in real-time equalization of PON transmission and (2) proposing RUM for real-time updating of weights in equalizers, which moves the quantification process from offline to real time, making the equalizers more robust for time-varying channels.
Assembling a global health image: Ethical and pragmatic tensions through the lenses of photographers
Authors: Alenichev Arsenii , de Laat Sonya , Solomon Nassisse , Suwalowska Halina , Peeters Grietens Koen , Parker Michael , Kingori Patricia 
Published: February 2024

Background
Recently, global health has been confronting its visual culture, historically modulated by colonialism, racism and abusive representation. There have been international calls to promote ethicality of visual practices. However, despite this focus on the history and the institutional use of global health images, little is known about how in practice contemporary images are created in communities, and how consent to be in photographs is obtained.

Methods
We conducted semi-structured interviews with 29 global health photographers about the ethical and practical challenges they experience in creating global health images, and thematically analysed the findings.

Findings
The following themes were identified: (1) global health photography is undergoing a marketing transformation and images are being increasingly moderated; (2) photographers routinely negotiate stereotypical and abusive tropes purposefully sought by organisations; (3) local scenes are modified, enhanced and staged to achieve a desired marketing effect; (4) ‘empowerment’ is becoming an increasingly prominent dehumanising visual trope; (5) consent to be photographed can be jeopardised by power imbalances, illiteracy, fears and trust; (6) organisations sometimes problematically recycle images.

Interpretation/Discussion
This research has identified practical and ethical issues experienced by global health photographers, suggesting that the production cycle of global health images can be easily abused. The detected themes raise questions of responsibility and accountability, and require further transdisciplinary discussion, especially if promoting ethical photojournalism is the goal for 21st century global health.
Partners’ experiences of their loved ones’ trauma and PTSD: An ongoing journey of loss and gain
Authors: Powling Rosie , Brown Dora , Tekin Sahra , Billings Jo 
Published: February 2024

Background
Traumatic life events can have a profound impact on the physical and psychological wellbeing of not only those who directly experience them, but others who are indirectly affected, such as victims’ partners.

Aims
This study aimed to explore the experiences and views of partners of individuals who have a history of trauma and diagnosis of posttraumatic stress disorder (PTSD).

Methods
In-depth semi-structured interviews were conducted with six partners of people who had experienced trauma and were diagnosed with PTSD and awaiting or receiving treatment at a specialist Trauma Service. The data was analysed using Interpretative Phenomenological Analysis.

Results
One overarching theme resulted from the data: partners experienced trauma and PTSD as an ongoing journey of loss and gain. This was supported by three superordinate themes: making sense of the trauma and ensuing consequences, shifting identities, and accessing and experiencing outside resources. Partners’ journeys were characterised by striving and struggling to make sense of the trauma and its ensuing consequences, whilst grappling with the identities of themselves, their partners and relationships shifting over time. Participants navigated their journeys in the context of external resources and support from friends, family, colleagues and professionals.

Conclusions
The results of this study highlight the need for greater information and support for partners of people with PTSD.
Evaluation of the DN-Mini (miniaturized double net) trap for sampling host-seeking Anopheles mosquitoes in malaria-endemic villages of southern Tanzania
Authors: Limwagu Alex J. , Msugupakulya Betwel J. , Kilalangongono Masoud M. , Mwalugelo Yohana A. , Okumu Fredros O. , Lyimo Issa N. , Ngasala Billy E. 
Published: February 2024

Background
Surveillance of malaria vectors is crucial for assessing the transmission risk and impact of control measures. Human landing catches (HLC) directly estimate the biting rates but raise ethical concerns due to the exposure of volunteers to mosquito-borne pathogens. A common alternative is the CDC-light trap, which is effective for catching host-seeking mosquitoes indoors but not outdoors. New, exposure-free methods are needed for sampling mosquitoes indoors and outdoors in ways that reflect their natural risk profiles. The aim of this study was therefore to evaluate the efficacy of the miniaturized double net trap (DN-Mini) for sampling host-seeking mosquitoes in south-eastern Tanzania, where malaria transmission is dominated by Anopheles funestus.

Methods
Adult mosquitoes were collected from 222 randomly selected houses across three villages (74 per village) in Ulanga district, south-eastern Tanzania, using the DN-Mini traps, CDC-Light traps, and Prokopack aspirators. First, we compared CDC-light and DN-Mini traps for collecting indoor host-seeking mosquitoes, while Prokopack aspirators were used for indoor-resting mosquitoes. Second, we deployed the DN-Mini and Prokopack aspirators to collect host-seeking and resting mosquitoes indoors and outdoors. Generalized linear mixed models (GLMM) with a negative binomial distribution were used to compare the effectiveness of the traps for catching different mosquito species.

Results
The DN-Mini was 1.53 times more efficient in collecting An. funestus indoors (RR = 1.53, 95% CI: 1.190–1.98) compared to the CDC-Light trap. However, for Anopheles arabiensis, the DN-Mini caught only 0.32 times as many mosquitoes indoors as the CDC-Light traps (RR = 0.32, 95% CI: 0.183–0.567). Both An. funestus and An. arabiensis were found to be more abundant indoors than outdoors when collected using the DN-Mini trap. Similarly, the Prokopack aspirator was greater indoors than outdoors for both An. funestus and An. arabiensis.

Conclusion
The DN-Mini outperformed the CDC-light trap in sampling the dominant malaria vector, An. funestus species, but was less effective in capturing An. arabiensis, and for both vector species, the biting risk was greater indoors than outdoors when measured using the DN-Mini trap. These findings highlight the importance of selecting appropriate trapping methods based on mosquito species and behaviors.
Co-design for stroke intervention development: Results of a scoping review
Authors: Singh Hardeep , Benn Natasha , Fung Agnes , Kokorelias Kristina M. , Martyniuk Julia , Nelson Michelle L. A. , Colquhoun Heather , Cameron Jill I. , Munce Sarah , Saragosa Marianne , Godhwani Kian , Khan Aleena , Yoo Paul Yejong , Kuluski Kerry 
Published: February 2024

Background
Co-design methodology seeks to actively engage end-users in developing interventions. It is increasingly used to design stroke interventions; however, limited guidance exists, particularly with/for individuals with stroke who have diverse cognitive, physical and functional abilities. Thus, we describe 1) the extent of existing research that has used co-design for stroke intervention development and 2) how co-design has been used to develop stroke interventions among studies that explicitly used co-design, including the rationale, types of co-designed stroke interventions, participants involved, research methodologies/approaches, methods of incorporating end-users in the research, co-design limitations, challenges and potential strategies reported by researchers.

Materials and methods
A scoping review informed by Joanna Briggs Institute and Arksey & O’Malley methodology was conducted by searching nine databases on December 21, 2022, to locate English-language literature that used co-design to develop a stroke intervention. Additional data sources were identified through a hand search. Data sources were de-duplicated, and two research team members reviewed their titles, abstracts and full text to ensure they met the inclusion criteria. Data relating to the research objectives were extracted, analyzed, and reported numerically and descriptively.

Results
Data sources used co-design for stroke intervention development with (n = 89) and without (n = 139) explicitly using the term ‘co-design.’ Among studies explicitly using co-design, it was commonly used to understand end-user needs and generate new ideas. Many co-designed interventions were technology-based (65%), and 48% were for physical rehabilitation or activity-based. Co-design was commonly conducted with multiple participants (82%; e.g., individuals with stroke, family members/caregivers and clinicians) and used various methods to engage end-users, including focus groups and workshops. Limitations, challenges and potential strategies for recruitment, participant-engagement, contextual and logistical and ethics of co-designed interventions were described.

Conclusions
Given the increasing popularity of co-design as a methodology for developing stroke interventions internationally, these findings can inform future co-designed studies.
Single versus bilateral internal thoracic artery grafting in patients with impaired renal function
Authors: Farkash Ariel , Gordon Amit , Mohr Rephael , Sela Orr , Pevni Dmitri , Ziv-Baran Tomer , Grupper Ayelet , Kfir Jonathan E. , Ben-Gal Yanai 
Published: February 2024

Objective
The optimal strategy for surgical revascularization in patients with impaired renal function is inconclusive. We compared early and late outcomes between bilateral internal thoracic artery (BITA) and single ITA (SITA) grafting in patients with renal dysfunction.

Methods
This is a retrospective analysis of all the patients with multivessel disease and impaired renal function (estimated glomerular filtration rate <60mL/min/1.73m2) who underwent isolated coronary artery bypass graft (CABG) in our center during 1996–2011, utilizing either BITA or SITA revascularization.

Results
Of the 5301 patients with multivessel disease who underwent surgical revascularization during the study period, 391 were with impaired renal function: 212 (54.2%) underwent BITA, 179 (45.8%) underwent SITA. Patients who underwent BITA were less likely to have comorbidities. Statistically significant differences were not observed between the BITA and SITA groups in 30-day mortality (5.6% vs. 9.0%, p = 0.2) and in rates of early stroke, myocardial infarction, and sternal infection (4.5% vs. 6.1%, p = 0.467; 1.7% vs. 2.8%, p = 0.517; and 2.2% vs. 5.7%, p = 0.088, respectively). Long-term survival of the BITA group was better: median 8.36 vs. 4.14 years, p<0.001. In multivariable analysis, BITA revascularization was associated with decreased late mortality (HR = 0.704, 95% CI: 0.556–0.89, p = 0.003). In analysis of a matched cohort (134 pairs), early outcomes did not differ between the groups; however, in multivariable analysis, BITA revascularization was associated with decreased late mortality ‎‎(HR = 0.35 (95%CI 0.18–0.68), p = 0.002)‎.

Conclusions
BITA revascularization did not impact early outcome in patients with CRF, but demonstrated a significant protective effect on long-term survival ‎in the unmatched and matched cohorts.
Legibus suis et suo iure utentes: las magistraturas epicóricas de los municipia antiquissima del Lacio
Authors: Torres-González Víctor Andrés 
Published: February 2024

El Lacio fue el primer territorio en el que la República romana comenzó en el siglo IV a. C. a extender su ciudadanía más allá de los muros de la Urbs y a crear un sistema descentralizado de administración local para las ciudades que iba anexionando, ya que Roma no dejaba de ser una ciudad-estado y, por tanto, su organigrama político no era capaz de asumir el gobierno directo de esas comunidades. Así surgieron los primeros municipia, denominados antiquissima por Cicerón, a los que se les permitió seguir autogobernándose según sus propias leyes e instituciones, lo que explica las diversas magistraturas epicóricas que hubo en esta región. En el presente trabajo se pretende ofrecer una visión de conjunto sobre los tres tipos de magistrados epicóricos existentes en el Lacio: dictator, praetores y aediles. De este modo, se llevará a cabo un estudio de las fuentes literarias y, sobre todo, epigráficas para establecer una relación entre el tipo de ciudadanía concedida (civitas optimo iure o sine suffragio), la etnia (latina, volsca, hérnica) y el régimen de magistrados en vigor en cada comunidad. Asimismo, se analizará el desarrollo y las funciones de estos magistrados epicóricos en cada uno de los antiguos municipios laciales para delimitar su ámbito de competencias y sus relaciones con el resto de los cargos cívicos y religiosos de la ciudad. Finalmente, se llegará a la conclusión de que la dictadura, la pretura y la edilidad epicóricas fueron una declaración orgullosa del pasado y de la antigua posesión de la ciudadanía romana por parte de estos municipia antiquissima frente a los ordenamientos de cuatorviros y duunviros de las comunidades cívicas romanas posteriores al Bellum Sociale, aunque el sistema más eficaz y evolucionado de estas últimas acabó ejerciendo una cierta influencia en el funcionamiento de estas magistraturas epicóricas laciales.