bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Language, Cognitive Competence, and Working Memory in Theory of Mind in Children on the Autism Spectrum
Authors: Ökcün-Akçamuş Meral Çilem , Tülü Burcu Kılıç , Ergül Cevriye
Published: January 2025

The development of Theory of Mind (ToM) is associated with variables such as language, working memory, and nonverbal cognitive competence. Children on the autism spectrum tend to have difficulties in ToM development, language and communication skills, and working memory. This study investigates relationships between language, working memory, and nonverbal cognitive competence with ToM in children on the autism spectrum. The study involved 40 children on the autism spectrum. Data collection tools included ToM tasks, the Turkish Early Language Development Test, Raven’s Colored Progressive Matrices, and the Working Memory Scale. As a result of this research, it was found that receptive language, expressive language, nonverbal cognitive competence, phonological loop, and central executive measures had significant relationships with ToM. The phonological loop and central executive measures were direct predictors of ToM. Nonverbal cognitive competence did not directly predict ToM but was mediated by the phonological loop and central executive.
The Nonclinical Safety Assessment of a Novel Anti-CEACAM5 Antibody Exatecan Conjugate Predicts a Low Risk for Interstitial Lung Disease (ILD) in Patients—The Putative Mechanism Behind ILD
Authors: Sloot Willem N. , Bertotti Elisa , Onidi Manuela , Paoletti Andrea , Salve Ilse De , Tavano Patrizia , Vigna Enrico , Mueller Gundi
Published: January 2025

The therapeutic window of antibody drug-conjugates (ADC) remains challenging due to safety issues such as interstitial lung disease (ILD) observed with specific deruxtecan-based ADCs. To avoid ILD, we designed M9140 by conjugating the maleimide-containing hydrophilic β-glucuronide linker to exatecan and our anti-CEACAM5 (CarcinoEmbryonic Antigen-related Cell Adhesion Molecule 5) specific antibody. Following repeated iv-infusion at 3 to 30 mg/kg of M9140 every 3 weeks, the pathological findings obtained in cynomolgus monkeys were confined to gastrointestinal and hematolymphoid tissues and resembled the toxicity of exatecan. At 24 mg/kg or higher, transient reductions in neutrophil and reticulocyte counts were observed with each dosing event along with reversible anemia throughout the study. The no observed adverse effect level was 24 mg/kg and the maximum tolerated dose was 30 mg/kg. The difference in toxicity by this small dose increment was correlated with a 2.5-fold difference in plasma exatecan exposure indicating antigen-independent toxicity. As anticipated, no lung toxicity was found with M9140 in these studies that were similar in study design to those used to confirm ILD with trastuzumab-deruxtecan in monkeys. Since the non-human primate model is regarded as predictive for the ILD risk in humans, this result indicates a low risk for ILD when applying M9140 to patients. The current M9140 safety data are discussed with special focus on the absence or presence of ILD with other antibody camptothecin-conjugates, for which a hypothetical pathogenic mechanism is postulated here. The favorable nonclinical profile of M9140 warrants further investigation in patients with CEACAM5-overexpressing tumors.
Two-Step Transfer Learning Improves Deep Learning–Based Drug Response Prediction in Small Datasets: A Case Study of Glioblastoma
Authors: Ju Jie , Ntafoulis Ioannis , Klein Michelle , JT Reinders Marcel , Lamfers Martine , P Stubbs Andrew , Li Yunlei
Published: January 2025

While deep learning (DL) is used in patients’ outcome predictions, the insufficiency of patient samples limits the accuracy. In this study, we investigated how transfer learning (TL) alleviates the small sample size problem. A 2-step TL framework was constructed for a difficult task: predicting the response of the drug temozolomide (TMZ) in glioblastoma (GBM) cell cultures. The GBM is aggressive, and most patients do not benefit from the only approved chemotherapeutic agent TMZ. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status is the only biomarker for TMZ responsiveness but has shown limited predictive power. The 2-step TL framework was built on 3 datasets: (1) the subset of the Genomics of Drug Sensitivity in Cancer (GDSC) dataset, including miscellaneous cell cultures treated by TMZ, cyclophosphamide, bortezomib, and oxaliplatin, as the source dataset; (2) the Human Glioblastoma Cell Culture (HGCC) dataset, for fine-tuning; and (3) a small target dataset GSE232173, for validation. The latter two included specifically TMZ-treated GBM cell cultures. The DL models were pretrained on the cell cultures treated by each of the 4 drugs from GDSC, respectively. Then, the DL models were refined on HGCC, where the best source drug was identified. Finally, the DL model was validated on GSE232173. Using 2-step TL with pretraining on oxaliplatin was not only superior to those without TL and with 1-step TL but also better than 3 benchmark methods, including MGMT. The oxaliplatin-based TL improved the performance probably by increasing the weights of cell cycle-related genes, which relates to the TMZ response processes. Our findings support the potential of oxaliplatin being an alternative therapy for patients with GBM and TL facilitating drug repurposing research. We recommend that following our methodology, using mixed cancers and a related drug as the source and then fine-tuning the model with the target cancer and the target drug will enhance drug response prediction.
Polycyclic Aromatic Hydrocarbons Burden of Meats Singed with Different Fuel Sources from Abattoirs in Ghana and Associated Cancer Risk Assessment
Authors: Abdulai Prosper Manu , Ossai Chika , Ezejiofor Anthoneth Ndidi , Frazzoli Chiara , Rovira Joaquim , Ekhator Osazuwa Clinton , Firempong Caleb Kesse , Orisakwe Orish Ebere
Published: January 2025

This study evaluated the concentrations of polycyclic aromatic hydrocarbons (PAHs) and the carcinogenic risks of cattle and goat meats singed with either firewood, Liquefied Petroleum Gas (LPG) or tyres from five cities in Ghana. The meat samples, before and after singeing, as well as after scraping and washing, were collected from abattoirs and sent to Clinical Analysis Laboratory (Can-Lab) of Kwame Nkrumah University of Science and Technology (KNUST) for PAH analysis. Tyre-singed meats exhibit significantly higher PAHs concentrations ( P = .01304) compared to those singed with firewood and LPG. Benzo[a]pyrene was the predominant PAH in tyre-singed cattle and goat meats, with concentrations of 23.1 mg/kg and 12.16 mg/kg, respectively. Washing singed meats reduced PAH levels, yet tyre-singed samples retained higher and dangerous concentrations than those singed with other fuels. Statistical analysis using ANOVA confirmed a significant effect of fuel type on PAH16 concentrations ( P = .01304). The Tukey HSD test indicated a significant difference between LPG and tyre ( P = .0105). Estimated daily intake (EDI) calculations highlighted potential health risks, particularly from tyre-singed meats, which exceeded regulatory limits set by health authorities. The findings emphasize the health hazards associated with consuming meats singed with tyres in Ghana and underscore the need for stringent regulatory measures and public awareness to mitigate PAH exposure.
Haunted by Gazaplatsen in our hearts: Exploring microfascist encounters in everyday activism
Authors: Kuyumcu Zeynep , Méndez-Grueso Gadea
Published: January 2025

This article explores the complex interplay between activism and academic research, particularly in the context of ongoing crises such as the genocide in Palestine and anti-gender politics. Drawing on ethnographic observations from two different research fieldworks and the experiences of anti-genocide activists, this article examines the persistent presence of the Palestinian issue in diverse contexts as a haunting feeling. Inspired by the insights from feminist ethnography and theory, we challenge the traditional separation of academic and activist identities, recognizing the influence of our academic knowledge and background as well as our activist experiences in shaping our understanding of contemporary political discourses and tensions at universities. As such, we analyse how seemingly minor acts of suppression and control within academic spaces and public life can be read through the concept of microfascism, and contribute to the broader silencing of dissent and the erosion of democratic principles. Through a nuanced exploration of microfascist encounters aimed at suppressing activism, such as purported security concerns regarding small informal student encounters organized for Palestine, and micro-regulations on putting up posters and announcements that permeate the daily lives of anti-genocide advocates, we discuss subtle yet pervasive forms of oppression that undermine academic freedom, social justice movements, and freedom of expression. Considering the growing presence of microfascist tactics in academia, we invite a reconsideration of the power systems that underpin universities in order to resist these oppressive forces within scholarly work and academic environments.
Retelling the past: Narrative construction and reconstruction using personal photographs and the elicitation of nostalgia
Authors: Elbaz Shira , Wiseman Hadas
Published: January 2025

While extensive research on nostalgia highlights its significance as a pancultural emotion which is experienced across the lifespan and which has various psychological benefits, qualitative research on the phenomenological and contextual aspects of nostalgia is limited. This article utilizes a constructivist approach to examine nostalgic narratives constructed in the process of selecting and discussing one’s personal photographs. The study aims to expand on the psychological benefits of nostalgia by focusing on the experiential and contextual aspects of this emotion. Eliciting nostalgia through participants’ childhood photographs during in-depth interviews revealed three strategies for reconstructing narrative and giving meaning to past events: (1) Mending the past; (2) Unchosen photographs; (3) Turning points. Utilizing nostalgia and personal photographs not only revealed implicit cultural context, but also assisted participants in creating continuity over time and enabled beneficial contact with complex and conflictual parts of self and biography. Therefore, this unique methodology has potential applications within qualitative research methods in psychology as well as within various therapeutic interventions.
Greater complexity and higher efficiency: Effects of translanguaging during collaborative pre-task planning on EFL learners’ speaking performance
Authors: Luo Xinran , Sun Peijian Paul
Published: January 2025

Translanguaging has thrived as a pedagogy for second language (L2) acquisition because of its potential in maximizing L2 learners’ communicative repertoire. However, limited attention has been paid to how translanguaging can influence L2 speaking within the framework of task-based language teaching (TBLT). This study explored how different language use (i.e., L2 only and translanguaging) in collaborative pre-task planning contributed to L2 learners’ subsequent monologic speaking performance, as measured by complexity, accuracy, fluency (CAF), and idea units. The planning behaviours were also examined to offer explanations for the differences in learners’ speaking performance. Altogether 72 undergraduate students from a Chinese university voluntarily participated in this study. The results showed that translanguaging planning contributed to the conceptualization stage of speech processing, as evidenced by gains in syntactic complexity and idea units. This positive effect might have resulted from enhanced communication efficiency due to translanguaging planning. The translanguaging group also generated more turns, produced more ideas on average, and devoted more time to vocabulary talk and task management. This was because translanguaging planning enabled learners to prioritize their language use for better task execution. In other words, the flexibility of translanguaging allows for a more strategic approach to language use, which can enhance collaborative efforts to successfully complete tasks. In contrast, the L2-only planning contributed to the formulation stage of speech processing, as was manifested in fewer mid-clause pauses. A trade-off between complexity and fluency was also observed in the study. Implications for the use of translanguaging in L2 speaking pedagogy are discussed.
Narrative and obesity: Managing weight stigma associated with bariatric surgery
Authors: Sicilia Álvaro , Socías-Serrano María-Luisa , Griffiths Mark D , Martínez-Rosales Elena , Artero Enrique G
Published: January 2025

The present study examined how individuals who have been clinically diagnosed as obese explain their decision to undergo bariatric surgery and how they deal with the stigmatization that such a decision may entail. A total of 23 participants (15 women and 8 men) who were awaiting bariatric surgery within the Spanish healthcare system, were interviewed about their weight trajectory and their decision to undergo this surgery. In order to examine the participants’ stories, a narrative analysis of the interviews was conducted, with attention to both content ( what they told) and structure ( how they told) and examining the stories in line with the socially and culturally available narratives that they had access to, and the context in which the stories were produced. The participants explained their weight trajectory through the origin of their weight, the failure to control it, and their decision to have surgery to solve the weight problem. The narrative of a sick body that needs to be restored appeared to function as a schema or script through which participants attempted to defend themselves from anti-fat narratives that assume personal failure while at the same time presenting themselves as deserving to be operated on. Through their narratives, they positioned themselves as undeserving of stigma but did not challenge the stigma itself.
Recycling potential of 3D printed support waste as eco-friendly polymeric composites
Authors: Mathiazhagan N , Palaniyappan Sabarinathan , Tamilselvan M , Sivakumar Narain Kumar
Published: January 2025

Nowadays 3D printing has excellent potential and attention over the traditional manufacturing technology and has more recycling possibilities. The present study focuses on the conversion of 3D printing raft support waste from the Fused Filament Fabrication (FFF) process and this waste can be converted into usable ecofriendly composites using ultrasonic joining technique. The joining study was done on the 3D printed supports of Poly Lactic Acid (PLA), Carbon fibre reinforced Poly Lactic Acid (CPLA), and Ceramic reinforced Poly Lactic Acid (CEPLA) samples. The samples are welded with 6 different combinations such as similar welding of PLA, CPLA and CEPLA, and dissimilar welding of CEPLA/CPLA, CEPLA/PLA, and CPLA/PLA. Similar and dissimilar ultrasonic welding was done with respect to varying the printing process parameters such as layer height, raster orientation and printing speed. The impact of various printing parameters on the joint possessions of the 3D printed supports was analysed in terms of the mechanical properties such as tensile strength and shore hardness value. The results show that, the maximum tensile strength was observed on the similar joints of Carbon fibre reinforced Poly Lactic Acid (CPLA) samples with layer height of 0.1 mm, printing speed of 20 mm/s and raster orientation of 90°. Fractured samples clearly shows that all the samples are failed under brittle mode of fracture and at lower printing speed the samples are evenly deposited, which results in proper bonding or fusion of the Joined raft support samples. This kind of refabrication method provides more benefit with lesser energy utilization compared to filament extrusion method for recycling of the 3D printed waste.
Suitability petitions, its evaluation process and US FDA’s response to the suitability petitions: Insights from the first half of GDUFA III
Authors: Chokshi Nirav , Modi Bhaumik , Raval Grishma
Published: January 2025

US FDA has committed to respond under GDUFA III within 6 months after Completeness Assessment (CA), up to a maximum of 50 suitability petitions. Underlining information in this article helps in understanding, the process of SP assessment as per GDUFA III and several reasons identified by the Agency for denial of suitability petitions. Assessment of US FDA's 48 SP responses (posted between October 1, 2023 and April 1, 2024) reveals that 50% of petitions were approved and 50% were denied. Amongst the approved 24 SPs, 71% petitions were related to the products delivered through oral route of administration and 29% related to the injectable injections. All the SPs related to the drug products delivered through opthalmic and topical route of administrations were denied. Majority of SPs were related to the additional strength proposal and least were related to the API change proposal. In 85% of the SP responses PREA was either not triggered or not evaluated by the US FDA while in 15% of the SP responses PREA was triggered due to proposed changes and full PREA waiver was granted in 86% of cases.
Protocol for optimizing robot-assisted autism therapy sessions through gaze analysis: A pilot study investigating optimal trial count for children with comorbid autism spectrum disorder and intellectual disability
Authors: Zahid Zunera , Ali Sara , Ayaz Yasar , Hassan Syed Mustafa , Nawaz Raheel
Published: January 2025

Background

Autism spectrum disorder poses challenges in social communication and behavior, while Intellectual disabilities are characterized by deficits in cognitive, social, and adaptive skills, frequently accompanied by stereotypies and challenging behaviors. Despite the progress made in autism spectrum disorder research, there is often a lack of research focusing on individuals with co-occurring autism spectrum disorder and intellectual disability. Robot-assisted autism therapies are effective in addressing these needs. However, there is a lack of consensus on the optimal number of therapy sessions required for effective outcomes, particularly in children with comorbid autism and intellectual disability.

Objectives

This study aims to investigate the optimal number of therapy sessions required for effective outcomes in robot-assisted autism therapy, specifically focusing on children with comorbid autism and intellectual disability. Gaze analysis metrics, including the average number of eye contact and average inter-eye contact delay, are utilized to assess therapy effectiveness.

Methods

This study integrates gaze analysis focusing on the average number of eye contact and average inter-eye contact delay as performance metrics. A pilot investigation was conducted to explore the critical temporal window for optimal trial count in robot-assisted autism therapy for children with autism. A mathematical model was introduced and validated for eight children with autism spectrum disorder, encompassing 56 experiments conducted over 7 weeks (one trial per week). Robots presented 8 cues in 3 categories (visual, speech, motion) with 16 cues per trial.

Results and Conclusions

The results, validated using single-sample Wilcoxon signed-rank tests, revealed that the unsaturated state, with a median score of 3.44, exhibited significantly lower average inter-eye contact delay (p-value = 0.014, r = 0.86) and significantly higher average number of eye contact (p-value = 0.014, r = 0.87) compared to the hypothesized medians. These findings suggest that the unsaturated state occurring in the critical temporal window has significantly higher average number of eye contact and lower average inter-eye contact delay compared to the saturated state. This study underscores the importance of tailored and targeted interventions for children with autism spectrum disorder, facilitating the development of cost-effective, time-efficient, evidence-based treatments.
Changing practices, procedures, and perceptions: A multi-year person-centered planning initiative in group homes for residents with intellectual and developmental disabilities
Authors: Blessing Carol , Brendli Brown Katherine R. , Pandey Toshna , Simmons Heather , O’Brien John
Published: January 2025

Person-centered planning has been shown to benefit people with disabilities and their quality of life. However, we have little knowledge of how person-centered planning can benefit staff and administration within a group home organization, as well as the extent to which it results in changes to organizational practices and procedures, as well as perceptions of people with disabilities. In this qualitative study, we explored the perspectives of organizational employees, an affiliating behavioral consultant, and residents with intellectual and developmental disabilities, taking into consideration key insights from person-centered planning consultant-coaches, to understand the effects of a person-centered planning initiative on the group home organization. Accompanying our findings are five stories that poetically describe each of the participating residents and their experiences with organizational employees throughout the implementation of the initiative. Implications for research and practice are discussed.
Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP): Study protocol and rationale
Authors: Yang Bin , Bai Xuesong , Yi Tingyu , Wang Haibo , Liu Yifeng , Ma Lin , Liu Sheng , Wu Shaoguang , Zhang Liyong , Peng Ya , Nogueira Raul G , Chen Wenhuo , Jiao Liqun
Published: January 2025

Rationale:

The Chemical Optimization of Cerebral Embolectomy (CHOICE) trial suggested that the administration of intra-arterial alteplase after successful endovascular thrombectomy (EVT) may improve neurological outcomes in patients with acute ischemic stroke due to large-vessel occlusion (AIS-LVO) in the anterior circulation. However, the use of adjunctive intra-arterial alteplase following successful EVT in acute posterior circulation stroke remains unexplored.

Aims:

This study aims to investigate the efficacy and safety of intra-arterial alteplase after successful EVT for AIS-LVO in the posterior circulation.

Sample size:

To detect an estimated 15% difference in the primary outcome between the two groups, a total of 376 patients will be enrolled. This sample size allows for 80% power and a 5% significance level, with an interim analysis planned after half of the sample (188 patients) has completed a 90-day follow-up.

Methods and design:

The Intra-arterial Alteplase Thrombolysis After Successful Thrombectomy for Acute Ischemic Stroke in the Posterior Circulation (IAT-TOP) trial is a multicenter, prospective, randomized clinical trial using an open-label treatment design with blinded endpoint assessment (PROBE) conducted in China. Patients with acute basilar artery occlusion will be randomly assigned in a 1:1 ratio to receive either intra-arterial alteplase (0.225 mg/kg; maximum dose, 22.5 mg) or standard care following successful thrombectomy (defined as expanded thrombolysis in cerebral infarction [eTICI] ⩾ 2b50).

Study outcomes:

The primary outcome is the modified Rankin Scale (mRS) score of 0–2 at 90 days. Key secondary outcomes include changes in eTICI scores after intra-arterial thrombolysis (in the experimental group), mRS 0–3 at 90 days, ordinal shift analysis of mRS at 90 days, early neurological improvement at 48 h, and improvement in National Institutes of Health Stroke Scale (NIHSS) scores at 48 h and 7 days or discharge. Safety outcomes include symptomatic intracranial hemorrhage (sICH) rates at 48 h, 90-day mortality, non-intracranial hemorrhagic complications, and non-hemorrhagic serious adverse events.

Discussion:

The IAT-TOP trial will provide crucial evidence regarding the potential benefits of adjunctive intra-arterial alteplase in patients with AIS-LVO in the posterior circulation following successful thrombectomy.

Trial registration:

ClinicalTrials.gov NCT05897554
Quantitative analysis of uncertainty in field data and calibration method for estimating life distribution parameters
Authors: Yang Kyungmin , Lee Dooyoul
Published: January 2025

In this study, to quantitatively evaluate the uncertainty of data input, electronic data, and handwritten data were compared and analyzed. Specifically, failure data of aircraft hydraulic actuators were used for failure trend and pattern analysis, descriptive statistical analysis, statistical lifetime analysis, and Bayesian network (BN) analysis. The field data used in weapons system reliability analysis uses electronic data from the Defense Logistics Integrated Information System (DELIIS). However, several issues have been identified in the quality of electronic data. To obtain meaningful results from reliability analysis, efforts are needed to reduce uncertainty in data input and improve quality. The analysis revealed that the quality of the electronic data was approximately 69% compared to the handwritten data. To address this issue, an integrated model based on Bayes’ theorem was presented. The integrated model increased the level of reliability analysis results by calibrating the parameters of the life distribution by combining the advantages of the two data types. The presented model can be continuously supplemented through Bayesian updates and is expected to be applicable to other weapon systems for which handwritten data exists.
Impact of thrombocytopenia on failure of endoscopic variceal treatment in cirrhotic patients with acute variceal bleeding
Authors: He Yan , Romeiro Fernando Gomes , Sun Mingyu , Ji Fanpu , Zhu Qiang , He Yingli , Ma Dapeng , Yuan Shanshan , Liu Xiaofeng , Philips Cyriac Abby , Basaranoglu Metin , Méndez-Sánchez Nahum , Pinyopornpanish Kanokwan , Li Yiling , Wu Yunhai , Yang Ling , Shao Lichun , Mancuso Andrea , Chen Yu , Tacke Frank , Lin Su , Liu Lei , Li Bimin , Qi Xingshun
Published: January 2025

Background:

Acute variceal bleeding (AVB), a life-threatening complication of liver cirrhosis, can be effectively treated by endoscopy, but there is a risk of early rebleeding after endoscopic variceal treatment (EVT). Thrombocytopenia is the most common hemostatic abnormality in liver cirrhosis. However, it is still unclear about whether thrombocytopenia increases the failure of EVT in cirrhotic patients with AVB.

Objectives:

We investigated the association between thrombocytopenia and the failure of EVT in cirrhotic patients with AVB.

Design:

International multicenter, retrospective study.

Methods:

Overall, 2467 cirrhotic patients with acute gastrointestinal bleeding who were enrolled into an international multicenter study between September 30, 2020 and June 30, 2023 were retrospectively screened. Thrombocytopenia was defined as platelet count below 150 × 109/L and further classified as mild (100 × 109/L–150 × 109/L), moderate (50 × 109/L–100 × 109/L), and severe (<50 × 109/L). A 1:1 propensity score matching (PSM) analysis was performed. Five-day failure to control bleeding was evaluated.

Results:

Overall, 1079 patients were included, of whom 923 (85.5%) had thrombocytopenia, including mild ( n = 241), moderate ( n = 445), and severe ( n = 237) thrombocytopenia. PSM analysis demonstrated that the rate of 5-day failure to control bleeding was not significantly different between patients with and without thrombocytopenia (mild: (12/153) 7.8% vs (7/153) 4.6%, p = 0.236; moderate: (9/155) 5.8% vs (7/155) 4.5%, p = 0.608; or severe: (5/132) 3.8% vs (7/132) 5.3%, p = 0.555).

Conclusion:

Thrombocytopenia may not influence the efficacy of EVT in cirrhotic patients with AVB.
Recent advances of antibody-drug conjugates in treating breast cancer with different HER2 status
Authors: Qiu Yue , Shi Yaqin , Chao Zhujun , Zhu Xinyu , Chen Yan , Lu Linlin
Published: January 2025

Despite the availability of multiple treatment options for breast cancer, challenges such as adverse events, drug resistance, and disease progression persist for patients. The identification of human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers, alongside the development of HER2-targeted therapies, has significantly improved the prognosis of HER2-amplified breast cancers. However, therapeutic options remain limited for HER2-overexpressing or HER2-negative breast cancers. In response to this gap, antibody-drug conjugates (ADCs) have emerged as a promising approach. ADCs combine the specificity of monoclonal antibodies with the cytotoxic effects of chemotherapy, which allows for the targeted delivery of a cytotoxic payload to cancer cells. ADCs have been used as adjuvant chemotherapeutic treatments and salvage therapies across various breast cancer subtypes, which have greatly improved the prognosis of breast cancer patients. Numerous ongoing clinical trials seek to optimize dosing strategies and identify patient populations that would benefit most from ADCs. This review presents an updated and comprehensive overview of emerging investigational ADCs for treating breast cancer patients with various HER2 subtypes. These ADCs are spearheading a new era in targeted cancer therapy, promising to innovate treatment paradigms for both HER2-positive and HER2-low breast cancers.
Cost-effectiveness of lazertinib as first-line treatment in patients with EGFR-mutated advanced lung cancer
Authors: Ku Li-Jung Elizabeth , Tsai Jui-Hung , Chen Li-Jun , Yang Szu-Chun
Published: January 2025

Background:

Lazertinib demonstrates efficacy similar to that of osimertinib in the first-line treatment of epidermal growth factor receptor ( EGFR)-mutated advanced lung cancer. However, its cost-effectiveness has not yet been evaluated.

Objective:

To study the cost-effectiveness of lazertinib as a first-line treatment for patients with EGFR-mutated advanced lung cancer.

Design:

A partitioned survival model-based cost-effectiveness analysis.

Methods:

We conducted the economic analysis from the perspective of the healthcare sector with a lifetime horizon. Simulated patients were entered into the models upon the diagnosis of EGFR-mutated advanced lung cancer. Lazertinib was compared with gefitinib. The model inputs were derived from the trials (survival outcomes, incidence of adverse events (AEs), and subsequent therapies), National Health Insurance payments (costs of drugs and AEs), and hospital cohorts (utility values). Deterministic and probabilistic analyses were also conducted.

Results:

Applying the same daily price of osimertinib (US$110) to that of lazertinib, the incremental cost-effectiveness ratio of lazertinib versus gefitinib was US$93,792 per quality-adjusted life year (QALY). The cost of lazertinib was a major determinant. If the daily price of lazertinib could be reduced to US$75, lazertinib would become cost-effective at a willingness-to-pay (WTP) threshold of US$70,000 per QALY. Given the WTP threshold, the probability that lazertinib would be cost-effective was 0.7%.

Conclusion:

Lazertinib is not a cost-effective first-line treatment for EGFR-mutated advanced lung cancer. Lowering prices enables cost-effectiveness.
Differential Effects of the Type of Physical Exercise on Blood Pressure in Independent Older Adults
Authors: Cancela-Carral Jose M. , Bezerra Pedro , Lopez-Rodriguez Adriana , Silva Bruno
Published: January 2025

Background:

Exercise and its effect on cardiovascular diseases have been extensively studied in the elderly population. The difference in blood pressure (BP) between fit and unfit subjects can be >5 mmHg. It is not well established whether the positive effects of exercising on BP are associated with exercise type, be it aerobic or anaerobic (maximal muscle strength).

Hypothesis:

Anaerobic training (maximal muscle strength) causes greater improvements than aerobic training on BP in active older adults.

Study Design:

Clinical trial.

Level of Evidence:

Level 4.

Methods:

This clinical trial was carried out with 202 participants (n = 116 aerobic program [ABPG], n = 86 strength program [SBPG]; 58.05% female; age 67.61 ± 5.01 years). The training program was carried out between 2018 and 2021. Periodic evaluations of BP (systolic BP [SBP] and diastolic BP [DBP]) were conducted with a frequency of twice per year. BP comparisons were made by using 2 × 2 analysis of variance with repeated measurements over the course of the 4 years of the project.

Results:

Throughout the training program, SBPG showed significant and consistent improvements in both SBP and DBP ( P < 0.01). On the other hand, the ABPG reported a significant initial improvement ( P < 0.01), which was not repeated in subsequent years. BP monitoring carried out over the 4 years showed a decrease in DBP and SBP, with this decrease being more pronounced in SBPG. However, the differences between the groups were not significant (2021; DBP, F = 1.227; P = 0.27; SBP, F = 0.826, P = 0.36).

Conclusion:

Among persons aged ≥65 years, muscle strength training programs appear to be more effective in inducing exercise-related positive changes in BP and cardiovascular risk factors compared with aerobic exercise programs.

Clinical Relevance:

Muscle strength training programs result in favorable changes in BP and cardiovascular risk factors.
SPI1 facilitates microfracture-mediated cartilage regeneration in the elderly by enhancing bone marrow stromal cells stemness
Authors: Wang Changjiang , Wang Yishu , Gu Yueqiang , Zhu Yi , Yin Rui , Li Yang , Gui Jianchao
Published: January 2025

Bone marrow stimulation treatment by bone marrow stromal cells (BMSCs) released from the bone medullary cavity and differentiated into cartilage via microfracture surgery is a frequently employed technique for treating articular cartilage injuries, yet the treatment presents a main drawback of poor cartilage regeneration in the elderly. Prior research indicated that aging could decrease the stemness capacity of BMSCs, thus we made a hypothesis that increasing old BMSCs (OBMSCs) stemness might improve the results of microfracture in the elderly. First, we investigated the correlation between microfracture outcomes and BMSCs stemness using clinical data and animal experiments. The outcomes of microfracture surgery in the elderly were significantly decreased as compared with the young counterparts while the stemness capacity of OBMSCs was also significantly decreased, and they were positively correlated. To investigate the role of BMSCs stemness in microfracture, we developed microfracture-mimic cartilage regeneration organoid models. In vitro experiments identified SPI1 as a potential stemness target gene, which could enhance the stemness and chondrogenesis of OBMSCs. The implantation of cartilage regeneration organoids made by SPI1-overexpressed OBMSCs could notably enhance cartilage regeneration in the old rats as compared with the microfracture treatment alone. Furthermore, molecular docking suggested a possible interaction between SPI1 and 5-Aza-2′-deoxycytidine (5Aza). The application of 5Aza could significantly improve the result of microfracture by upregulating SPI1. In summary, we identified SPI1 as a novel stemness target of OBMSCs, which was beneficial for the improvement of microfracture-stimulated cartilage regeneration in the elderly.
Neoliberalism, citizenship, and young children: Exploring discursive constructions of citizenship in early childhood curricula in China and Aotearoa New Zealand
Authors: Xu Peng , Ritchie Jenny
Published: January 2025

As an entitlement to rights, well-being and equity, young children’s citizenship lays the foundation for a democratic, just and sustainable world. This article interrogates the discursive constructions of ‘citizenship’ within recent early childhood curriculum documents in China and Aotearoa New Zealand. Since the 1990s, both nations have released national curricula to facilitate children’s growth and learning, unveiling the potential of children to act as competent and active citizens. A previous study explained ways in which citizenship in both nations’ curricula is discursively constructed as a ‘neoliberal construction’. However, other possible constructions of children’s citizenship are worthy of exploration. This article draws from the first author’s doctoral study and further examines alternative discursive constructions of children’s citizenship in both nations’ curricula to address this research gap. Engaging a post-structural positioning that incorporates critiques of power and knowledge drawing from the work of Michel Foucault, we present examples of ways that young children’s citizenship is discursively constructed as (1) development and preparation, (2) rights and participation and (3) relationships and connectedness. The power of cultural and historical discourses in creating these constructions is explored, whereby neoliberal discourse may either be problematised or strengthened.
Cyclosporine-induced thrombotic microangiopathy in pregnant women: A case report and literature review
Authors: Zhang Su , Zhou Hai-hui , Zhong Zi-xing , Wang Qi-qi , Huang Ping , Liu Su-xiao
Published: January 2025

Cyclosporine A (CsA) is a commonly used immunosuppressant, but its association with thrombotic microangiopathy (TMA) is rarely reported. In recent years, CsA has been used in pregnant women with autoimmune diseases or previous immune-related adverse pregnancies. Our case involves a 34-year-old female who developed typical laboratory indicators of TMA while using CsA to improve pregnancy outcomes. After discontinuing CsA, the TMA markers gradually normalized. To our knowledge, this is the first report of CsA-induced TMA during pregnancy. We also reviewed previous case reports of CsA-induced TMA and summarized the possible mechanisms, characteristics, and risk factors, as well as methods to identify this rare adverse effect of CsA in pregnant women.
Providers’ Beliefs and Values: Understanding Their Approach to Gender-Affirming Care
Authors: Shirin Ahona , Daniello Maya , Stamm Laura
Published: January 2025

Objectives:

This qualitative study explored the beliefs and values influencing healthcare providers’ delivery of gender-affirming care (GAC) to transgender and gender-diverse (TGD) youth amidst current social and political dynamics.

Methods:

The study PI conducted 43 semi-structured interviews with providers across states with varying GAC legislation. Responses from 41 providers were analyzed in this paper. A thematic approach to data analysis was employed using qualitative coding.

Results:

Key themes emerged: criteria for treatment, ethical and moral considerations, and professional and personal responsibility. Providers widely endorsed GAC as evidence-based and essential for alleviating distress and promoting autonomy. They emphasized the importance of respecting patients’ gender identities and viewing GAC as life-saving.

Conclusion:

Despite legislative challenges, the study highlights a strong consensus among providers on the medical necessity of GAC for TGD youth.
An inborn error of metabolism presenting with apparently isolated subacute neuropsychiatric symptoms in an adolescent
Authors: Engel Sarah Grace , Al-Beshri Ali Said , Ananth Amitha , Rashid Salman
Published: January 2025

We discuss a previously healthy adolescent male presenting with subacute neuropsychiatric issues, tremors, hyperreflexia, and hypertension. Laboratory studies revealed acute imposed on chronic kidney disease. Additional investigations yielded a treatable late-onset inborn error of metabolism (IEM). Late-onset forms of IEMs may present very differently than early-onset disease manifestations (e.g., neuropsychiatric issues may be the predominant symptom), thus leading to the under-recognition of a treatable underlying etiology.
The Role of Ethics in Organizational Internal Communication—A Synthesis and Agenda
Authors: Anand Amitabh , Sinitsyna Elena , Shantakumar Varsha P. , Lašáková Anna , Oyner Olga Konstantinovna
Published: January 2025

In organizational and management studies, ethical issues associated with internal communication (IC) have been understudied and are marked by a lack of systematic study examining the function of ethics within the organizational framework. This research seeks to address the shortcomings by conducting a comprehensive literature review of the ethical stance of IC. We first address the evolution of ethics within the framework of ICA and establish that managers play a pivotal role in assuring the effectiveness of IC through ethical practices. Second, we elucidate the essential themes of ethical information communication at three requisite levels by detailing the antecedents and consequences of these levels: individual, organizational and management. Lastly, we present a guiding framework that delineates the role of ethics in IC and proposes pathways for future exploration.
Rental Arrears and Perceived Risk of Eviction among U.S. Renter Households by Household Composition, Race, and Ethnicity 2020 to 2024
Authors: Fusaro Vincent A. , Collier K. Megan , Baidoo Christopher , Coley Rebekah Levine
Published: January 2025

This visualization presents trends in the estimated proportion of U.S. renter households in arrears and their perceived risk of eviction from August 2020 through June 2024 constructed using the Household Pulse Survey, a nationally representative repeated cross-sectional survey fielded by the U.S. Census Bureau. The proportion of renter households in arrears fell following the initial shock of the coronavirus pandemic and an increasing fraction of renters felt that eviction was unlikely. The proportion of renters perceiving some risk and high risk for eviction both generally fell over time. These patterns were evident for all demographic subgroups, but there were clear and persistent disparities. Black and Hispanic households reported higher rates of both rental arrears and perceived risk for eviction throughout the time period compared with White households. Households with children had higher rates of rental arrears and perceived eviction risk compared with households without children within each racial and ethnic demographic subgroup.
Cervical Cancer and Cervical Cancer Screening in Women with HIV in Guangxi, China: A Model Simulation Study
Authors: Zhao Ran , Kulasingam Shalini
Published: January 2025

Background. Cervical cancer screening can effectively reduce the disease burden. In China, the current cervical cancer screening guidelines do not provide separate screening recommendations for women living with HIV (WLWH) to account for their increased risk. Methods. We developed a comprehensive individual-based simulation model to provide evidence to support tailored cervical cancer screening programs for WLWH in Guangxi, a region with a high prevalence of HIV in China. Compared with the current screening coverage (i.e., the status quo), we evaluated the benefits and the harms associated with 9 cytology-based cervical cancer screenings tailored to WLWH in Guangxi. The 9 strategies vary in terms of screening interval (every 1, 3, or 5 y) and the age to exit screening (at age 65 y, 85 y, or no exit). Results. All screening strategies evaluated were effective in reducing cervical cancers and cancer deaths among WLWH. Compared with the status quo, the percentage reduction in total cancers ranged from 18% to 60%, and the percentage reduction in cancer deaths ranged from 20% to 62%. Strategies with a 3- or 5-y screening interval had lower numbers of colposcopies per cancer and cancer deaths prevented. Conclusion. Implementing cytology-based cervical cancer screening among WLWH in Guangxi, China, can effectively prevent cervical cancer cases and cancer deaths. Our results suggest that adopting an older end age and a shorter screening interval might be more effective in preventing cancer cases and deaths but may also be associated with more screenings and potential harms and costs, while adopting a 3- or 5-y screening interval may provide a more reasonable balance of benefits and harms to prevent future cancer cases and deaths among WLWH in Guangxi, China.

Highlights

Our comprehensive model can be used to evaluate various health interventions that aim to reduce the disease burden caused by HPV and cervical cancer. Cytology-based cervical cancer screening tailored to WLWH in Guangxi, China can effectively prevent cervical cancer cases and cancer deaths. Adopting a 3- or 5-y screening interval may provide a more reasonable balance of benefits and harms to prevent future cancer cases and deaths.
Rescue therapy after failed thrombectomy in medium/distal vessel occlusions: A retrospective analysis of an international, multi-center registry
Authors: Anastasiou Aikaterini , Brehm Alex , Dobrocky Tomas , Mujanovic Adnan , de Dios Lascuevas Marta , Carmona Fuentes Tomas , López-Frías López-Jurado Alfonso , Hidalgo Valverde Blanca , Berlis Ansgar , Maurer Christoph J. , Nguyen Thanh N , Abdalkader Mohamad , Klein Piers , Thevoz Guillaume , Michel Patrik , Kaschner Marius , Weiss Daniel , Alexandre Andrea M. , Pedicelli Alessandro , Machi Paolo , Bernava Gianmarco , Kuwahara Shuntaro , Uchida Kazutaka , Wenderoth Jason , Joshi Anirudh , Karwacki Grzegorz , Lakatos Lehel-Barna , Tessitore Agostino , Vinci Sergio Lucio , Cervo Amedeo , Rollo Claudia , Hui Ferdinand , Mozumder Aaisha Siddiqua , Romano Daniele Giuseppe , Flora Gianmarco , Goyal Nitin , Batra Vivek , Inoa Violiza , Cognard Christophe , Hoferica Matúš , Rautio Riitta , Kaiser Daniel , Alph Hanna , Clarke Julian , Hug Nick , Koch Alma , Schulze-Zachau Victor , Rommers Nikki , Katan Mira , Psychogios Marios-Nikos
Published: January 2025

Background:

There are limited therapeutic options in cases of failed reperfusion (modified thrombolysis in cerebral infarction [mTICI] score < 2b) after stent-retriever and/or aspiration based endovascular treatment (EVT) for acute ischemic stroke. Despite the absence of data supporting its use, rescue therapy (balloon angioplasty and/or stent implantation) is often utilized in such cases. Studies are limited to large vessel occlusions, while the outcomes and complications after rescue therapy in medium/distal vessel occlusions (MDVOs) have not been reported. This study aims to report the outcomes of rescue therapy in MDVO stroke patients.

Methods:

We performed an analysis of the “Blood pressure and Antiplatelet medication management after reScue angioplasty after failed Endovascular treatment in Large and distal vessel occlusions with probable IntraCranial Atherosclerotic Disease” (BASEL ICAD) retrospective registry. All MDVO stroke patients were included in the analysis.

Results:

Out of the 718 registry patients, 87 (12.1%) presented with an MDVO. Fifty-six patients (64.4%) showed an occlusion of the M2 segment of the middle cerebral artery. Rescue stenting was performed in 78 patients (89.7%) while balloon angioplasty alone was performed in 9 patients (10.3%). Successful reperfusion (mTICI score ⩾ 2b) was achieved in 73 (83.9%) patients after rescue therapy. Symptomatic intracranial hemorrhage (sICH) occurred in 8 patients (9.2%) and post-treatment stent occlusion in 12 patients (13.8%). Ninety days mortality was 20.7%. Twenty-eight patients (32.2%) achieved functional independence at 90 days (modified Rankin Scale 0–2).

Conclusion:

Rescue therapy with stenting and/or balloon angioplasty in patients undergoing EVT for isolated MDVO with suspected underlying intracranial atherosclerotic disease is an effective reperfusion strategy but is associated with complications and poor functional outcomes.