bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case report: Selpercatinib in the treatment of RET fusion-positive advanced lung adenocarcinoma: a challenging clinical case
Authors: Pagliaro Raffaella , Medusa Paola Maria , Vitiello Fabiana , Aronne Luigi , Campbell Susan F. M. , Perrotta Fabio , Bianco Andrea 
Published: January 2025

BackgroundRearranged during transfection (RET) fusions represent a distinct molecular subset of non-small cell lung cancer (NSCLC) with targeted therapeutic potential. Selpercatinib, a highly selective RET inhibitor, has demonstrated efficacy in various solid tumors harboring RET alterations. Here, we present a case highlighting the use and clinical outcomes of selpercatinib in a patient diagnosed with advanced lung adenocarcinoma harboring a RET fusion.Case presentationA 59-year-old woman with a history of stage IV lung adenocarcinoma harboring a KIF5B-RET fusion presented with disease progression following first-line chemo-immunotherapy. Selpercatinib was initiated as a targeted therapy, leading to a notable radiographic response and clinical improvement. The patient experienced a significant reduction in tumor burden and reported improved symptom control, with no significant adverse effects during the 21-month follow-up period.ConclusionsThis case highlights the efficacy and tolerability of selpercatinib in treating advanced lung adenocarcinoma with a RET fusion. The observed clinical response supports the early use of selpercatinib as a targeted therapy for RET fusion-positive NSCLC, including in patients with compromised general and respiratory conditions, especially in cases refractory to conventional treatments. Long-term follow-up studies are warranted to validate these findings and assess the durability of responses.
Responsiveness and clinical utility of PROMIS instruments in pediatric Crohn's disease: insights from a longitudinal study
Authors: Azevedo Sara , Oliveira Maria Miguel , Nogueira Paulo , Lopes Ana Isabel 
Published: January 2025

BackgroundInflammatory bowel disease (IBD) may adversely affect physical, psychological, and social well-being. Integrating patient-reported outcomes (PROs) into clinical practice is crucial for comprehensive disease management.ObjectiveTo evaluate the responsiveness and clinical utility of Patient-Reported Outcomes Measurement Information System (PROMIS) instruments, compared with standard clinical assessment tools in pediatric CD patients.MethodsA longitudinal, prospective study with 31 pediatric Crohn's disease (CD) patients aged 8–17 years recruited from a Pediatric Gastroenterology Unit. Data were collected at baseline and every 6 months over 18 months. PROMIS pediatric measures assessed PROs. Disease activity was evaluated using the pediatric Crohn's disease activity index (PCDAI) and clinical markers. IMPACT-III was also applied. Linear mixed-effects models (LMMs) and bivariate analyses were used to assess changes over time.ResultsPROMIS Global Health scores showed significant improvement over time, indicating enhanced overall health perceptions among patients. Notable reductions were observed in PROMIS Pain Interference and Fatigue scores, indicating better physical health. PROMIS depression scores generally decreased, suggesting improved mental health. PCDAI scores, hemoglobin, and platelet count significantly changed and correlated with PROMIS measures. Globally, the study demonstrated significant and clinically relevant changes in multiple PROMIS measures, confirming their responsiveness to changes in disease activity.ConclusionPROMIS instruments are clinically useful in managing pediatric CD, providing valuable insights into global health and quality of life. Integrating PROMIS measures into routine clinical practice may enhance disease management and treatment strategies for pediatric IBD patients.
External negative pressure improves lung aeration in near-term rabbit kittens at risk of developing respiratory distress
Authors: Diedericks C. , Crossley K. J. , Jurkschat D. , Wallace M. J. , Davies I. M. , Riddington P. J. , te Pas A. B. , Kitchen M. J. , Hooper S. B. 
Published: January 2025

IntroductionAs airway liquid is cleared into lung interstitial tissue after birth, the chest wall must expand to accommodate this liquid and the incoming air. We examined the effect of applying external positive and negative pressures to the chest wall on lung aeration in near-term rabbit kittens at risk of developing respiratory distress.MethodsRabbit kittens (30 days; term ∼31 days) were randomised into Control and Elevated Liquid (EL) groups. Lung liquid was drained in Control kittens to simulate expected volumes following vaginal delivery. EL kittens had lung liquid drained before 30 ml/kg was returned to simulate expected volumes after caesarean section. Kittens were delivered, placed in a water-filled plethysmograph and the external pressure was adjusted to −6 (negative), 0 (atmospheric), or +6 (positive) cmH2O. Kittens were ventilated with an 8 ml/kg tidal volume and PEEP of 0 cmH2O and lungs imaged using phase contrast x-ray imaging.ResultsCompared to external atmospheric pressures, external negative pressures expanded the chest (by 2100 ± 43 vs. 1805 ± 59 mm2; Control kittens; P = 0.028), directed tidal ventilation into lower, larger lung regions and increased functional residual capacity (FRC) levels in both Control (26.7 ± 2.0 vs. 12.6 ± 2.2 ml/kg; P &lt; 0.001) and EL (19.6 ± 1.6 vs. 10.0 ± 2.9 ml/kg; P &lt; 0.01) kittens. External positive pressures reduced FRC levels in Control (6.3 ± 0.8 vs. 12.6 ± 2.2 ml/kg; P &lt; 0.05), but not in EL kittens, and directed tidal ventilation into upper lung regions.DiscussionExternal negative pressures increased lung aeration and resulted in a more evenly distributed tidal ventilation immediately after birth in near-term rabbit kittens, whereas external positive pressures reduced lung aeration and compliance.
A review of the Bovis Calculus’s intervention mechanism and clinical application in ischemic stroke
Authors: Xu Ke , Deng Bowen , Jia Tongtong , Ren Mihong , Chen Hai , Zhang Jing , Guo Jinlin , Li Yong , Wang Jian 
Published: January 2025

BackgroundBovis Calculus (BC), also named Niuhuang in Chinese, is utilized as a resuscitation drug in Traditional Chinese Medicine (TCM) for the treatment of neurological disorders. Ischemic stroke (IS) is a significant global public health issue that currently lacks safe and effective therapeutic drugs. Ongoing efforts are focused on identifying effective treatment strategies from Traditional, Complementary, and Integrative Medicine. Noticeably, BC has been used in TCM for thousands of years to prevent or treat IS-related diseases.MethodsThe historical origins of BC in the treatment of IS were investigated through the examination of ancient Chinese medical texts. Furthermore, the chemical components of BC were analyzed, and its mechanisms of action against IS were summarized using literature sourced from databases such as Web of Science, PubMed, and China National Knowledge Infrastructure. Information on Chinese medicine preparations and clinical reports was also integrated to provide an overview of modern applications and safety considerations.ResultsBC mainly includes chemical components such as bile pigments, bile acids, cholesterol, proteins amino acids, and trace elements. Additionally, the efficacy of BC in treating cerebral ischemia/reperfusion injury (CI/RI) is certain, particularly due to the components of bile pigments, bile acids, and amino acids that can interfere with the enzymatic cascade reaction of CI/RI through multiple components, targets, and pathways. The active components of BC exert neuroprotective effects by reducing microcirculation disturbance, excitatory amino acid toxicity, and oxidative stress injury in the acute stage; inhibiting inflammatory injury, apoptosis, and blood-brain barrier (BBB) disruption in the subacute stage; and promoting angiogenesis and neurogenesis in the restoration stage. Furthermore, as a crude drug, BC appears in many Chinese patent medicine (CPM) preparations for the treatment of IS, and clinical and preclinical studies have proved its safety.ConclusionThe use of BC in the treatment of IS has a long history, proven efficacy, and widespread application. Future efforts should focus on elucidating its mechanisms of action and exploring its applications.
Large variability in the alkaloid content of Corydalis yanhusuo dietary supplements
Authors: Luis Paula B. , Schneider Claus 
Published: January 2025

IntroductionExtracts from the rhizome of the traditional Chinese medicinal plant Corydalis yanhusuo (CY) mediate a number of biologic effects that are associated with its content of isoquinoline alkaloids. CY alkaloids have shown analgesic, cardioprotective, and anti-addictive effects in animal models of disease. Since CY alkaloids are available to consumers as dietary supplements we analyzed the content of alkaloids in 14 products including open powders, capsules, and liquid formulations, capturing a majority of the products available online in the US.MethodsNineteen alkaloids were quantified using HPLC analyses with diode array detection after extraction using a weak cation exchange column.ResultsTotal alkaloid content was highly variable among the products, ranging from below quantifiable in some to ≈11 mg/g in others. Five of the products had comparable content of alkaloids (9.5 ± 1.6 mg/g), equaling about the amount of alkaloids of an extract prepared from CY rhizome (12.7 mg/g). The other samples had much lower content (1.8 ± 0.9 mg/g), or alkaloids were below quantifiable. One of the products was highly enriched in tetrahydropalmatine (≈5 mg/g), suggesting adulteration from the natural product, and raising concerns about possible toxicologic liability.DiscussionConsidering alkaloid content as a key quality criterium for CY supplements, the large variability among the products seems unacceptable and makes it difficult for consumers to select products with an appropriate content of alkaloids.
Case Report: Targeted treatment by fluoxetine/norfluoxetine of a KCNC2 variant causing developmental and epileptic encephalopathy
Authors: Li Ping , Butler Alice , Zhou Yu , Magleby Karl L. , Gurnett Christina A. , Salkoff Lawrence 
Published: January 2025

The Kv3.2 subfamily of voltage activated potassium channels encoded by the KCNC2 gene is abundantly expressed in neurons that fire trains of fast action potentials that are a major source of cortical inhibition. Gain-of-function (GOF) de novo pathogenic variants in KCNC1 and KCNC2, encoding Kv3.1 and Kv3.2 respectively, cause several types of epilepsy including developmental and epileptic encephalopathy (DEE). Fluoxetine (Prozac) is a known inhibitor of the Kv3.1 current and was reported to improve seizure control in a single patient with a KCNC1 GOF variant. Here, we describe fluoxetine treatment of two siblings with a de novo KCNC2 V473A variant associated with DEE, which resulted in improved seizure control, ability to wean antiepileptic medications, and improved development. The KCNC2 V437A variant showed GOF activity as demonstrated by HEK293 cells expressing variant subunits activating at more hyperpolarized potentials than WT channels. Fluoxetine reduced currents equally for both Kv3.2 WT and Kv3.2-V473A variant channels, with an IC50 of ∼12 µM. Further analysis of this repurposed drug showed that norfluoxetine, a long-lasting metabolite of fluoxetine which is produced in the liver and accumulates in the brain, was more effective than fluoxetine itself in selectively inhibiting the dominant pathogenic channel activity of the pathogenic allele. Norfluoxetine showed 7-fold greater selectivity in inhibiting Kv3.2 variant currents (IC50 of ∼0.4 µM) compared to WT currents (IC50 of ∼2.9 µM). Combined with a previous report of improved outcomes for a KCNC1 variant, our results suggest that fluoxetine or its metabolite, norfluoxetine, may be beneficial for patients with GOF variants in KCNC2 and other neuronal potassium channels.
Opportune moments for task interruptions: examining the cognitive mechanisms underlying interruption-timing effects
Authors: Hirsch Patricia , Moretti Luca , Leichtmann Benedikt , Koch Iring , Nitsch Verena 
Published: January 2025

IntroductionSeveral studies showed that task interruptions at high mental workload moments are more harmful than task interruptions at low mental workload moments. In the present study, we used a theory-driven approach to define the mental workload during primary-task execution and to examine the effects of the interruption timing on primary-task performance.MethodsParticipants performed a primary task comprising a pre-defined sequence of six subtasks, with task interruptions occasionally occurring before the second, third, or fourth subtasks. Critically, the subtasks were organized either in two lag-2 repetition triplets or in two lag-2 switch triplets (e.g., ABA-CBC vs. CBA-CAB). This set-up allowed us to test two predictions about the effects of interruption timing on the resumption costs (i.e., the performance in subtasks following an interruption compared to the performance in the same subtask in non-interrupted primary tasks). First, we expected task interruptions before the fourth subtask being the less detrimental due to the presumed chunking of the six subtasks into two triplets. Second, in lag-2 switch triplets, task interruptions before the second and third subtasks were predicted to result in comparable resumption costs. In contrast, in lag-2 repetition triplets, task interruptions before the third subtask were hypothesized to be more disruptive than those before the second subtask. This is because the mental workload should be higher due to the need to overcome subtask inhibition.ResultsWe found an interruption-timing effect with higher resumption costs for task interruptions occurring before the third subtask compared to interruptions before the second and the fourth subtasks. However, this effect did not differ across lag-2 repetition sequences and lag-2 switch sequences.DiscussionThese findings are discussed from a memory perspective and a context reconstruction perspective.
Co-creating a person-centered creative engagement intervention for Parkinson's care
Authors: Spee Blanca T. M. , Stap Thieme B. , Plijnaer Marjoke , Pasman Gert , Zeggio Sara , Duits Annelien , Crone Julia S. , Haeyen Suzanne , Pelowski Matthew , Bloem Bastiaan R. , Koksma Jan-Jurjen 
Published: January 2025

BackgroundRecent research in the field of “Arts and Health” has demonstrated the beneficial impact of arts-based interventions on health and well-being across diverse populations. Recognizing their potential, especially in cases where conventional healthcare cannot address the multifaceted impact of conditions such as in Parkinson's disease (PD), our study advocates for an integrative approach in medical practice and neuroscience. We recommend incorporating learning environments from the design phase through long-term care. The arts offer a unique opportunity to create such environments. In this study, we specifically focus on individuals with PD, co-designing an intervention as a creative engagement learning environment and a PD-specific creative arts therapy. In this study, the narratives of those affected contribute as scientific knowledge, shaping care and increasing the intervention's relevance to participants' lives.MethodsWe used a participatory design-based research approach. Fourteen individuals with PD, along with three creative therapists and three researchers, collaborated through iterative design cycles to co-develop a creative arts therapy intervention. Qualitative data were collected through interviews, group reflections, and ethnographic observations. Data were analyzed using reflexive thematic analysis.ResultsThe co-creation process resulted in a 10-week creative engagement intervention delivered in a “creative playground” setting. Participants chose from multiple media and autonomously decided their creative activities. Guidance from the creative therapists was provided as needed to support individual engagement and guide reflection and learning processes. Narratives offered insights into the relevance of autonomy in care, the role of the arts, and the individuality of disease experience, resulting in seven key features of our intervention framework, which include (i) intervention structure (e.g., duration of the intervention and sessions), (ii) freedom in selection of creative media, (iii) environment as a creative playground, (iv) skills of creative therapists, (v) PD-specific considerations, (vi) financial considerations and logistics, and we list (vii) responsibilities of the Design Team.DiscussionThis study establishes an initial framework for a PD-specific creative arts therapy intervention designed as a creative engagement learning environment. Future research will focus on rigorously evaluating its effectiveness and exploring its scalability in diverse settings.
Imprint of ancestral and modern threats in human mind – experience of fear, disgust, and anger
Authors: Landová Eva , Polák Jakub , Janovcová Markéta , Štolhoferová Iveta , Peterková Šárka , Chomik Aleksandra , Frynta Daniel 
Published: January 2025

IntroductionThreats to our survival are often posed by the environment in which humans have evolved or live today. Animal and human ancestors developed complex physiological and behavioral response systems to cope with two types of threats: immediate physical harm from predators or conspecifics, triggering fear, and the risk of infections from parasites and pathogens leading to the evolution of the behavioral immune system (BIS) with disgust as the key emotion. Here we ask whether the BIS has adapted to protect us from pandemic risks or poisoning by modern toxic substances.MethodsWe have developed a survey comprised of 60 vignettes describing threats evoking fear and disgust belonging to one of the three main categories of threats: (1) ancestral, (2) modern, and (3) pandemic of airborne disease. Each vignette was evaluated on a 7-point Likert scale based on fear, disgust, and anger. Respondents also completed an assessment battery.ResultsThe results show that the strongest fear is triggered by modern threats (electricity, car accidents), while the highest disgust is evoked by ancient threats (body waste products, worms). Disgust does not respond to modern threat stimuli such as toxic substances or radioactivity as these evoke mainly fear and anger. A discriminant factor analysis classified nine out of 10 pandemic disgust vignettes into the ancestral disgust category, convincingly assigning the pandemic disgust threats to the ancestral type. Gender, age, and type of education were significant moderators of emotional responses across all threat categories.DiscussionOur study reveals that while fear is more context-dependent, particularly triggered by modern threats, disgust operates on an evolutionarily hardwired basis, making it less effective against contemporary risks. Furthermore, disgust experienced during a pandemic outbreak is more closely aligned with ancestral disgust-related threats tapping into evolutionary ancient survival circuits of the BIS. However, as disgust declines with age, the brain must adaptatively shift the emotional processing from disgust to fear to protect older adults from contamination risks. Finally, our study reveals that pandemic fear is better predicted by specific behaviors rather than general anxiety, suggesting a need for new assessments.
Attribution theory of poverty and beliefs about charity in Malaysia: an inter-ethnic comparison
Authors: Khan Abidullah , Shafiai Muhammad Hakimi Mohd , Abbas Ghulam , Zaidi Syeda Beena , Hassan Mehboob Ul 
Published: January 2025

IntroductionMalaysia as an ethnically diverse country has a history of interethnic inequality and poverty which led to the development of different views about the existence of poverty. Among these ethnic groups, some sympathize with the poor and help them through different charity organizations. However, these charity organizations are mostly unaware of the target donors that can aid their charity funds. Therefore, this study explores the attitudinal differences regarding poverty among Malays, Chinese, and Indians and the demographic groups that can be targeted for donation and social policy development purposes.MethodologyA survey is conducted in Selangor, where the data through a questionnaire is extracted from the three ethnic groups. Through the quota sampling technique, a sample of 700 is derived. The results are analyzed through ANOVA, regression, and mediation analysis.ResultsThe results show that attitudinal differences between Malays and Chinese regarding structuralist beliefs could be observed. Moreover, among Malays, it is found that the relationship between gender, income, education, wealth, and structuralist beliefs is significantly mediated by beliefs about charity. On the other hand, mediation analysis for Chinese identifies gender, education, and income while among Indians gender, education, and wealth are identified as key demographic groups.DiscussionThis study highlights the role of attribution theory to identify the charity donors among the different ethnic groups which was overshadowed by the previous research in Malaysia. The results also hold significance for charity institutions to target the specified groups through their marketing campaigns. Also, based on these results government can reduce the misconception about the existence of poverty and to develop policies that encourage high income groups to support the poor.
Why can parents’ phubbing affect mobile phone addiction? Perspective of the I-PACE model
Authors: Liu Bo , Xu Hemuqing , Wei Hua , Song Yuancai 
Published: January 2025

ObjectiveBased on the I-PACE model, this study investigated the longitudinal relationship between parents’ phubbing and mobile phone addiction, as well as the serial mediating effects of maladaptive cognition and ego depletion.MethodsA longitudinal study, with data collected at two time points over a six-month interval to test the proposed hypotheses. The independent variable was measured at Time 1 (T1), while the mediators and dependent variables were assessed at Time 2 (T2). A total of 591 middle school students from a city in central China was recruited to complete the parents’ phubbing scale, maladaptive cognition scale, ego depletion scale and mobile phone addiction scale.Results(1) The correlation analysis showed a significant positive correlation between T1 parents’ phubbing, T2 maladaptive cognition, T2 ego depletion, and T2 mobile phone addiction. (2) Maladaptive cognition was found to mediate the relationship between parent’s phubbing and mobile phone addiction. Similarly, ego depletion also mediated the relationship between parent’s phubbing and mobile phone addiction. Additionally, both maladaptive cognition and ego depletion functioned as serial mediators between parent’s phubbing and mobile phone addiction.ConclusionThis study provides evidence that parental phubbing serves as a longitudinal predictor of mobile phone addiction, with maladaptive cognition and ego depletion acting as key mediators in this process.