bluuebunny/crossref_metadata_2025 huggingface dataset:
Metastatic SQSTM1-NTRK1 fused non-small-cell lung cancer treated with larotrectinib and stereotactic radiosurgery resulting in durable complete response: a case report
Authors: Betts Colton , Kassardjian Ari , Amini Arya
Published: February 2025

Lung cancer is one of the most common malignancies and causes the most cancer deaths in the United States. Targeted therapies have improved the survival of patients with advanced disease. Neurotrophic tropomyosin receptor kinase (NTRK) fusions are a rare oncogenic driver that has been targeted with the tumor-agnostic drug, larotrectinib. There are limited data on the treatment of non-small-cell lung cancer (NSCLC) with larotrectinib because of the rarity of this fusion in this population. We present the case of a patient who was diagnosed with SQSTM1-NTRK1 fused NSCLC with polymetastatic disease involving the brain and subsequently treated with a multidisciplinary approach via neurosurgical resection, radiotherapy, and larotrectinib. The combination of aggressive local treatments and systemic therapy is a relatively new treatment paradigm and represents a new area of research to optimize local control of metastatic lesions and potentially improve progression-free survival compared to the trials that show the efficacy of systemic monotherapies. The patient has experienced a sustained complete response to treatment almost 3 years later, and he has tolerated the drug without any significant adverse effects. The combination of systemic therapy with larotrectinib and aggressive local treatments could benefit patients with targetable fusions even with multiple metastatic lesions.
High TCTA expression is an adverse prognostic biomarker in acute myeloid leukemia
Authors: Shao Yunli , Qin Tong
Published: February 2025

Background

Acute myeloid leukemia (AML) prognosis varies greatly, underscoring the need for novel biomarkers to improve patient stratification. T-cell leukemia translocation-associated gene (TCTA) has emerged as a potential player in hematological malignancies, yet its role in AML remains unexplored.

Objective

To investigate the prognostic significance of TCTA in AML and elucidate its functional mechanisms.

Methods

RNA sequencing data from 173 AML patients (TCGA) and 70 normal controls (GTEx) were analyzed. Patients were categorized into high and low TCTA expression groups. Bioinformatics tools assessed Gene Ontology, KEGG pathways, and immune infiltration and constructed a nomogram predicting 1–5-year overall survival (OS).

Results

High TCTA expression correlated with significantly reduced OS ( P < 0.001), with multivariate analysis identifying TCTA expression alongside age and cytogenetic risk as independent OS predictors. Receiver operating characteristic analysis validated TCTA's diagnostic potential. Enrichment analyses implicated TCTA in pathways critical to AML, such as hematopoiesis, p53 signaling, and DNA methylation, with a notable association with natural killer (NK) cell activity.

Conclusions

Elevated TCTA expression signifies poor prognosis in AML, positioning it as a promising prognostic biomarker. Its involvement in key AML-related pathways highlights TCTA's functional relevance and potential as a therapeutic target in AML management.
Determination of Total Flavonoid Content and Phenolic Content, Antioxidant Assay, and Antiepileptic Activity of Achillea millefolium Extract
Authors: Hayat Sonia , Miana G. A. , Kanwal Madiha , Ahsan Zartab , Tariq Muhammad Junaid
Published: February 2025

Objectives

This study aimed to evaluate the antioxidant and antiepileptic potential of the ethanolic extract of Achillea millefolium aerial parts. Antioxidant activity was measured using DPPH photometric assay, and flavonoid content was quantified via the aluminum chloride method. The extract's neuroprotective effect was assessed using the pentylenetetrazole (PTZ)-induced seizure model, along with immunohistochemical (IHC) analysis and hematoxylin & eosin (H&E) staining.

Methods

The antioxidant potential of the extract was determined through DPPH radical scavenging activity, while flavonoid content was assessed as quercetin equivalents (QE). The in vivo antiepileptic activity was evaluated in mice using the PTZ-induced seizure model. Key biomarkers of oxidative stress, including glutathione (GSH), glutathione-S-transferase (GST), catalase, and lipid peroxidation (LPO), were measured to evaluate the extract's ability to ameliorate PTZ-induced oxidative stress.

Results

The extract demonstrated notable antioxidant activity, with 72% scavenging activity observed at 900 µg/mL. Flavonoid content was determined to be 39.45 ± 1.84 µg QE/mg. In the PTZ-induced seizure model, Achillea millefolium extract at 400 mg/kg and 600 mg/kg significantly reduced neuroinflammatory markers and oxidative stress, as evidenced by decreased LPO and increased levels of GSH, GST, and catalase. IHC and H&E staining revealed neuroprotective effects, including reduced neuroinflammation and enhanced neuronal survival.

Conclusion

The ethanolic extract of Achillea millefolium exhibited strong antioxidant and neuroprotective properties, effectively mitigating PTZ-induced seizures, oxidative stress, and inflammatory responses. These findings suggest its potential as a natural alternative for epilepsy treatment.
Concordance of maternal and cord blood SARS-COV-2 immunoglobulin seropositivity after COVID-19 infection or vaccination in pregnancy
Authors: Rojas Gladys , Jain Aarti , Bany-Mohammed Fayez , Felgner Philip , Aslam Muhammad , Uy Cherry C
Published: February 2025

Objective

To assess maternal antibody response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection during pregnancy and subsequent transplacental antibody transfer in cord blood.

Study Design

This is a prospective cohort study of Coronavirus Disease 2019 (COVID-19) polymerase chain reaction (PCR) positive pregnant women and their newborns. SARS-CoV-2 PCR (+) women were enrolled, with SARS-CoV-2 PCR (−) as control. Maternal blood was obtained at enrollment and cord blood collected at delivery. Baseline maternal and infant characteristics and neonatal outcomes were collected. Samples were analyzed using coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2 (including nucleocapsid protein [NP], spike protein [S], S1, S2, receptor-binding domain [RBD]) which can detect SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM).

Results

Thirty-seven maternal-cord blood paired samples were analyzed for SARS-CoV-2 IgG or IgM antibodies; 15 out of 20 samples from SARS-CoV-2 PCR (+) and 14 out of 17 from SARS-CoV-2 PCR (−) mothers were IgG positive. 14 out of the 17 SARS-CoV-2 PCR (−) mothers received COVID-19 vaccine during pregnancy. Difference between IgG seropositivity of naturally infected versus vaccinated mothers were significant, 75% versus 100% ( p = 0.043). IgM antibodies were detected in 10 out of 20 SARS-CoV-2 PCR (+) women but none were detected in cord blood.

Conclusions

Excellent concordance of SARS-CoV-2 IgG antibodies exist between maternal and cord blood. Significantly higher SARS-COV-2 cord blood IgG seropositivity was found in vaccinated versus naturally infected mothers.
Infantile myofibromatosis: Small bumps pose big problems
Authors: Lee Hillary C , Amin Amee A , Chikwava Kudakwashe R , Smith Valeria R , Fernandes Caraciolo J
Published: February 2025

Background

Infantile myofibromatosis (IM) is a disorder characterized by proliferation of benign myofibroblastic tumors that typically manifest as solitary or multiple nodules in the skin, muscle, bone, subcutaneous tissues, and visceral organs and can pose significant morbidity and mortality risks, particularly in cases involving visceral organs or causing functional impairment. These soft tissue lesions are the most prevalent benign fibrous tumors that present before age two and can undergo spontaneous regression or are amenable to surgical resection.

Case

A preterm, male infant was born via Caesarean section to a mother with a trichorionic, triamniotic pregnancy following preterm labor. Within the first week of life, several well-circumscribed, smooth, non-tender, and soft nodules with some mobility were noticed along the border of the ribs, across the trunk, back, and lower extremities. Ultrasound imaging confirmed well-circumscribed hypoechoic, intramuscular nodules, and biopsy evaluation showed atypical spindle cell proliferation. The biopsied lesion was PDGFRB-mutated on molecular genetic studies, confirming a diagnosis of myofibromatosis. The infant developed mixed lytic and sclerotic deformities of a variety of bones, necessitating treatment given disease progression.

Conclusion

Successful clinical management with low-dose metronomic chemotherapy (methotrexate and vinblastine) is possible and can treat extensive disease, as seen in our patient.
Early postnatal weight changes in opioid-exposed infants managed using the Finnegan Neonatal Abstinence Scoring System Versus Eat, Sleep, Console
Authors: Dennison Emma , Coo Helen , Khurshid Faiza
Published: February 2025

Background

Despite the many clinical benefits of Eat, Sleep, Console (ESC) to manage infants with neonatal abstinence syndrome (NAS), a recent article theorized that ESC may place infants at an increased risk of excessive postnatal weight loss. The objective of this study was to compare weight changes in the early postnatal period among infants exposed to opioids in utero and managed using 1) the Finnegan Neonatal Abstinence Scoring System (FNASS) or 2) ESC.

Methods

Pre-post analysis of medical records for opioid-exposed infants born July 1, 2017-May 31, 2023. Type of feeding (exclusive breastfeeding, formula only, combination) and weight changes were compared between the FNASS (n = 45) and ESC (n = 25) groups.

Results

Type of feeding differed significantly between the groups during the first 5 days of life and at discharge: higher proportions of the FNASS group were exclusively breastfed and higher proportions of the ESC group received formula. There were no significant differences in daily weight changes over the first 5 days of life when we controlled for type of feeding. The average daily weight change during hospitalization did not differ significantly between the two groups (FNASS: median = −53.3 grams/day [IQR: −65.2, −40.8]; ESC: median = −45.9 [IQR: −57.8, −25.5]; p = 0.19).

Conclusions

We found no evidence of excessive weight loss in the early postnatal period among opioid-exposed infants managed using ESC as compared to FNASS. However, our findings suggest that breastfeeding should be more actively promoted and supported when centers transition from the FNASS model to ESC.
A Graceful Business: A Catalog of Lessons Learned About Qualitative Inquiry From a Lifetime of Reading Beyond the Canon
Authors: Nordstrom Susan Naomi
Published: February 2025

In this article, I catalog the lessons I have learned from reading beyond the qualitative inquiry canon. The catalog offers lessons based on seven infinitive verbs and/or verb phrases—to be patient, to tend, to linger, to love, to not say anything and/or say something, to be humble, and to listen. These inquiry lessons are drawn from a lifetime of reading poetry, numerous genres of fiction, nonfiction, plays, and other texts. These verbs and lessons materialize an iteration of qualitative inquiry that is characterized as a graceful business that centers ethical practices.
Effects of Supramaximal Intensity Interval Training on Resistin and Cardiometabolic Health Indices in Overweight Nonpostmenopausal Women
Authors: Mohammadnia Ahmadi Mohsen , Najarian Effat , Nezamdoost Zeynab , Sadeghi-Tabas Saber , Abtahi Eivary Seyed Hosein
Published: February 2025

Background:

Adipose tissue is an endocrine organ that produces various bioactive molecules known as adipokines, including resistin, which is be highly expressed in people with obesity and cardiovascular disease (CVD). The effects of supramaximal high intensity interval training (HIIT) and moderate-intensity interval training (MIIT) on serum levels of resistin and various cardiometabolic health indices, were investigated.

Hypothesis:

Supramaximal and moderate interval training induce comparable effects on serum resistin levels and cardiometabolic health indices.

Study Design:

Cohort study.

Methods:

Thirty overweight adult women were assigned to 1 of 3 groups: HIIT (2 sets of 8 intervals, each with 30 seconds exercise at 100%-110% maximal aerobic speed [MAS] followed by 30 seconds rest at 50% MAS; for 6 weeks with 3 sessions per week), MIIT (2 sets of 8 intervals, each with 30 seconds exercise at 70%-80% MAS followed by 30 seconds rest at 50% MAS; for 6 weeks with 3 sessions per week), or a control group.

Results:

Triglyceride levels were significantly higher in the control group compared with both the HIIT and MIIT groups ( P = .02 and .01, respectively). High-density lipoprotein levels were also elevated significantly in the experimental groups compared with the control group ( P = .04 and .03, respectively). Serum resistin increased significantly from pretest levels in the control group ( P < .01). Between-group comparisons showed that resistin levels were significantly higher in the control group than in the experimental groups ( P < .01 and .01, respectively).

Conclusion:

Six weeks of HIIT can reduce resistin levels and improve cardiometabolic health indicators in nonpostmenopausal women. Although 6 weeks of MIIT does not reduce resistin, it does decrease systolic blood pressure and obesity-related factors in nonmenopausal women.

Clinical Relevance:

Supramaximal interval training may be recommended to control bioactive molecules produced from adipose tissue that are linked to CVD.
Advances in tissue engineering of peripheral nerve and tissue innervation – a systematic review
Authors: Sueters Jayson , van Heiningen Rowan , de Vries Ralph , Guler Zeliha , Huirne Judith , Smit Theo
Published: February 2025

Although various options are available to treat injured organs and peripheral nerves, none is without limitations. Auto- and allografts are the first choice of treatment, but tissue survival or functionality is not guaranteed due to often limited vascular and neural networks. In response, tissue-engineered solutions have been developed, yet clinical translations is rare. In this study, a systematic review was performed on tissue-engineered advancements for peripheral nerves and tissues, to aid future developments in bridging the gap toward the clinic by identifying high-potential solutions and unexplored areas. A systematic search was performed in PubMed, Embase, Web of Science, and Scopus until November 9, 2023. Search terms involved “tissue engineering,” “guided,” “tissue scaffold,” and “tissue graft,” together with “innervation” and “reinnervation.” Original in vivo or in vitro studies meeting the inclusion criteria (tissue-engineered peripheral nerve/innervation of tissue) and no exclusion criteria (no full text available; written in foreign language; nonoriginal article; tissue-engineering of central nervous system; publication before 2012; insufficient study quality or reproducibility) were assessed. A total of 68 out of 3626 original studies were included. Data extraction was based on disease model, cell origin and host species, biomaterial nature and composition, and external stimuli of biological, chemical or physical origin. Although tissue engineering is still in its infancy, explored innervation strategies of today were highlighted with respect to biomaterials, cell types, and external stimuli. The findings emphasize that natural biomaterials, pre-seeding with autologous cell sources, and solutions for reproductive organs are beneficial for future research. Natural biomaterials possess important cues required for cell-material interaction and closely resemble native tissue in terms of biomechanical, geometrical and chemical composition. Autologous cells induce biomaterial functionalization. As these solutions pose no risk of immunorejection and have demonstrated good outcomes, they are most likely to fulfill the clinical demands.
Mapping materials, drawing Europe: Sample and data quality and accessibility in the biobanking infrastructure BBMRI-ERIC
Authors: Aarden Erik
Published: February 2025

The European biobanking infrastructure BBMRI-ERIC was established in the context of European Union science policy to facilitate collaboration between European repositories of biological samples and associated data, or so-called biobanks. To allow the exchange of research materials, the infrastructure has created several platforms for quality management and making materials visible and accessible. In this article, I develop the metaphor of mapping to explore the workings of these platforms. I consider maps as devices for giving directions, as representations of science, and as (symbolic) outlines of the territory of Europe to explore how BBMRI-ERIC's activities in quality management and IT-platforms for making materials visible and accessible (aim to) facilitate circulation. Across the different platforms, efforts to harmonize and integrate European biobanking activities confront both scientific and European tendencies toward fragmentation. The map of a European biobanking community drawn by BBMRI-ERIC consequently both makes and unmakes Europe sketching a Europe of both harmonization and fragmentation. In laying bare these paradoxical effects of the construction of a European biobanking infrastructure, using mapping as a lens shows how, rather than realizing its much-cited role as a “facilitator” for research, BBMRI-ERIC embodies key tensions at the center of efforts to advance “data-based” (big) science.
Urban revitalization pathways toward zero carbon emissions through systems architecting of urban digital twins
Authors: Ramnarine Ishwar D , Sherif Tarek A , Alorabi Abdulrahman H , Helmy Haya , Yoshida Takahiro , Murayama Akito , Yang Perry P-J
Published: February 2025

Recognizing the critical role of cities in mitigating greenhouse gas emissions, many cities are adopting carbon neutrality goals as part of their climate action strategies. The efficacy of these initiatives, however, has been undermined by complexity of systemic problems, ineffectiveness in planning implementation, and lack of stakeholder engagement. Urban and community-level carbon reduction should transcend urban design and systems optimization to incorporate multi-faceted dimensions in urban contexts. To address these challenges, this paper proposes a framework of urban digital twins that includes digital representation, performance modeling, design interventions and interactive platform for decisions over temporal processes. The CANVAS, or Carbon Neutrality Architecting New Visions for Architectural Systems, is a systems architecting approach to modeling the process of urban revitalization for achieving carbon neutrality by 2050. The developed workflow integrates multidisciplinary approaches for carbon mapping, gap identification, alternative generation, Urban Building Energy Modeling (UBEM) simulation, evaluation, and decision-making to demonstrates applicability of the proposed framework through a case study of the Nihonbashi district in Tokyo. The approach revealed that Energy Use Intensity (EUI) can be decreased by 99 kWh/m2/y through reconstruction and operational improvements. Emerging photovoltaic technologies can further cut EUI by an average of 42.5 kWh/m2/y, although results vary significantly in respect to building characteristics, particularly geometry and floor area. The incremental, cyclical systems architecting approach revealed that a 97% reduction in carbon emissions could be achieved by the seventh cycle through stakeholder-centric system interventions. This paper contributes to the development of urban digital twin methodologies by integrating systems architecting concepts with UBEM as transformative tools for carbon neutral urban design and development.
The Subjectivity Discourse of Indigenous Peoples Self Media in Taiwan
Authors: Lin Fu Yueh
Published: February 2025

In recent years, Taiwan's grassroots Indigenous alternative media has seen the rise of a significant number of Indigenous online social media platforms. When mainstream media or social media present news or opinions regarding Indigenous peoples, these Indigenous social media outlets actively present Indigenous perspectives on the issues. They voice their positions from an ethnic subjectivity standpoint, attempting to deconstruct and critique the hegemonic discourse conveyed by mainstream society and media, exposing the ideologies they produce and reproduce, as well as the power structures they construct. The analysis in this study focuses primarily on the discourse from two of the most vocal and radical Indigenous social media fan pages: “Buan Moon Speaks Moon Calendar” and “A Daily Dose of Bunun Language! mapasnava Bunun saikin” The selected discourse texts cover the period from 2020 to 2024, beginning by listing the more significant Indigenous social issues during this period, alongside the mainstream societal narratives presented in response. Following this, the study outlines the discourse expressed by Indigenous social media after these events and conducts a discourse analysis of these responses. The research primarily examines how the discourse created and published by these Indigenous social media platforms constructs and expresses “counter-discourse” against mainstream societal perspectives, develops strategies for resistance, and highlights various discourse methods for the reassertion of Indigenous subjectivity. It also demonstrates how they position themselves and assert their right to interpret and voice their perspectives.
Relationships Among PTSD, Trait Mindfulness, and Factors of SUD in Veterans Enrolled in Specialty SUD Treatment
Authors: Rehder Kristoffer , Morasco Benjamin J. , Bowen Sarah
Published: February 2025

Objective:

A growing body of evidence points to a role for mindfulness in the development or maintenance of co-occurring posttraumatic stress disorder (PTSD) and substance use disorder (SUD). However, the mechanisms of this relationship remain unclear in the veteran population. This study seeks to understand how PTSD and facets of mindfulness are associated with factors of SUD in veterans enrolled in a VA specialty SUD treatment program.

Method:

Veterans enrolled in the SUD treatment program were recruited from group classes and waiting rooms, and completed measures assessing SUD-related factors of frequency of alcohol use, hazardous alcohol use, consequences from substance use, and craving, as well as PTSD symptoms, mindfulness facets, and depressive symptoms. Three hierarchical multiple regressions assessed the extent to which significant relationships between mindfulness and SUD-related factors exist beyond associations commonly found with PTSD, depression, and craving.

Results:

Participants (n = 159) were predominately male (91.2%) and White (86.2%) (age: Mean = 57.3; SD = 12.9). After controlling for demographic factors, PTSD, and clinical variables, mindfulness facets were associated with SUD-related factors; observe was positively related to frequency of alcohol use, non-judging was positively related to hazardous alcohol use, and non-reactivity was negatively associated with consequences from use. Exploratory analyses suggested that non-reactivity mediated the relationship between PTSD and consequences from use.

Conclusions:

Facets of observe, non-judging, and non-reactivity may help explain relationships between PTSD and SUD-related factors. However, associations with non-judging and observe were in the opposite direction hypothesized. More research is needed to understand positive associations between mindfulness and factors of SUD in veteran samples.
Effects of polypropylene glycol-treated montmorillonite/carbon black as a filler with rubber compound properties
Authors: Asghari Barzegar Zohreh , Malekzadeh Mercedeh
Published: February 2025

Carbon black is commonly used as a filler in the rubber industry. However, it can cause serious damage to human health and to ecosystems. Today, reducing the use of this substance via alternative materials is receiving increased attention. Clay minerals such as montmorillonite can be substituted for carbon black as environmentally friendly fillers for rubber compounds. The uniform dispersion of montmorillonite and its compatibility with the rubber matrix are the main principles for using this material in the rubber industry. To this end, montmorillonite was surface treated with various dosages (1.0, 1.5 and 2.0 wt.%) of polypropylene glycol. The surface-treated montmorillonites were investigated using attenuated total reflection Fourier-transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy and X-ray diffraction analysis. The results indicated that the treatment expanded the interlayer spaces of the montmorillonite and improved surface hydrophobicity. The untreated and treated montmorillonites were used with carbon black as dual fillers in natural rubber/styrene butadiene-based compounds. The cure characteristics, thermal stability, some mechanical properties and dispersion states were evaluated. The curing study indicated a faster optimum cure time, scorch time and increased torque difference for the rubber compounds filled with surface-treated montmorillonites. Thermal analysis of the rubber compounds illustrated that the interval between the initial and final temperature of decomposition could be increased via the treatment. Surface-treated montmorillonite samples, especially the sample containing 1 wt.% polypropylene glycol, showed improved abrasion resistance, resilience and compression set values.
Phase II trial of ibrutinib and nivolumab in patients with relapsed CNS lymphomas
Authors: Chihara Dai , Steiner Raphael E. , Nair Ranjit , Feng Lei , Ahmed Sairah , Strati Paolo , Malpica Castillo Luis E , Griffith Donna , Mathew Shivon A , Montinez Wirt , Masand Gita , Samaniego Felipe , Rodriguez Maria Alma , Hagemeister Fredrick B. , Fayad Luis E. , Iyer Swaminathan P. , Nastoupil Loretta J. , Neelapu Sattva S. , Flowers Christopher R , Westin Jason R
Published: February 2025

Treatment options are limited for both relapsed/refractory primary and secondary central nervous system (CNS) lymphoma and the prognosis remains poor. Prior studies have shown the activity of Bruton tyrosine kinase (BTK) inhibitors and programmed death-1 targeted therapies in CNS lymphoma and studies suggested potential synergy. Therefore, we conducted a phase 2 trial combining ibrutinib with nivolumab for patients with relapsed/refractory CNS lymphoma. Patients received ibrutinib 560mg oral daily with nivolumab 240mg IV every 14 days (28-days per cycle). Patients who were in partial or complete response after 6 cycles of treatment could continue therapy for up to 2 years unless progression or unacceptable toxicity. Eighteen patients were enrolled with the median age was 63 years (range 43-88). The median number of prior lines of therapy was 2 (range, 1-4), 55% had refractory disease, 17% had prior stem cell transplant, and 11% had prior CAR T-cell therapy. The best overall response rate was 78% and the best complete response rate was 50% (95% CI: 26-74%). The median PFS and OS was 6.5 months and 21.0 months, respectively and three patients continue to be in remission over two years. Treatment was generally well tolerated but two patients stopped treatment due to fatigue. Ibrutinib and nivolumab resulted in reasonable safety and clinical activity in patients with refractory/relapsed CNS lymphoma and warrants further investigation. NCT03770416
Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a Phase II study
Authors: Westin Jason R , Phillips Tycel J. , Mehta Amitkumar , Hoffmann Marc S , Gonzalez-Barca Eva , Thieblemont Catherine , Bastos-Oreiro Mariana , Greil Richard , Giebel Sebastian , Wei Michael C. , Wang Jue , Bucher Reinhard , Sit Jason , Penuel Elicia , Purev Enkhtsetseg , Yee Donald L , Bergua Burgues Juan Miguel
Published: February 2025

This Phase II study evaluated mosunetuzumab plus cyclophosphamide, doxorubicin, prednisone, and polatuzumab vedotin (Pola-M-CHP) versus Pola-rituximab (R)-CHP for first-line treatment of diffuse large B-cell lymphoma (DLBCL). Patients were randomized 2:1 to receive 6 cycles of Pola-M-CHP or Pola-R-CHP on Day 1 of each 21-day cycle. Mosunetuzumab was administered intravenously via step-up dosing during Cycle 1 and at 30 mg on Day 1 of subsequent cycles. The primary endpoint was Independent Review Committee-assessed complete response (CR) rate by positron emission tomography-computed tomography. Overall, 62 patients were enrolled and received Pola-M-CHP (n = 40) or Pola-R-CHP (n = 22). CR rates were similar in both arms (72.5% with Pola-M-CHP versus 77.3% with Pola-R-CHP); the 24-month investigator-assessed progression-free survival rate was 70.8% (95% CI, 55.6-86.1) with Pola-M-CHP versus 81.8% (95% CI, 65.7-97.9) with Pola-R-CHP. The most common adverse event (AE) was cytokine release syndrome (68.4%; mostly Grade 1 [52.6%], and primarily confined to Cycle 1) with Pola-M-CHP and neutropenia/neutrophil count decreased (54.5%) with Pola-R-CHP. Neutropenia/neutrophil count decreased was the most frequently observed Grade ≥3 AE in both arms (Pola-M-CHP: 36.8%; Pola-R-CHP: 22.7%). Rates of Grade ≥3 AEs (86.8% versus 59.1%), serious AEs (63.2% versus 13.6%), and AEs leading to treatment discontinuation (13.2% versus 0%) were higher with Pola-M-CHP than Pola-R-CHP, respectively. Pharmacodynamic changes were supportive of mosunetuzumab's mechanism of action and its addition to the Pola-CHP combination. Pola-M-CHP, although an active combination, did not demonstrate a clinical benefit over Pola-R-CHP in this small study. This trial was registered at www.clinicaltrials.gov as #NCT03677141.
The effect of storage time and temperature on the proteomic analysis of FFPE tissue sections
Authors: Koh Jennifer M. S. , Sykes Erin K. , Rukhaya Jyoti , Anees Asim , Zhong Qing , Jackson Christopher , Panizza Benedict J. , Reddel Roger R. , Balleine Rosemary L. , Hains Peter G. , Robinson Phillip J.
Published: February 2025

Formalin-fixed paraffin-embedded (FFPE) tissues present an important resource for cancer proteomics. They are more readily available than fresh frozen (FF) tissues and can be stored at ambient temperature for decades. FFPE blocks are largely stable for long-term preservation of tumour histology, but the antigenicity of some proteins in FFPE sections degrades over time resulting in deteriorating performance of immunohistochemistry (IHC). It is not known whether FFPE sections that have previously been cut from blocks and used for liquid chromatography-mass spectrometry (LC–MS) analysis at a later time are affected by storage time or temperature. We determined the stability of FFPE sections stored at room temperature (RT) versus − 80 °C over 48 weeks. The stored sections were processed at different timepoints (n = 11) and compared to sections that were freshly cut from FFPE blocks at each timepoint (controls). A total of 297 sections (rat brain, kidney and liver stored at RT, − 80 °C or freshly cut) were tryptically digested and analysed on TripleTOF 6600 mass spectrometers in data-dependent acquisition (DDA) mode. Kidney and liver digests were also analysed in data-independent acquisition (DIA) mode. The number of proteins and peptides identified by DDA with ProteinPilot and some common post-translational modifications (PTMs) were unaffected by the storage time or temperature. Nine of the most common FFPE-associated modifications were quantified using DIA data and all were unaffected by storage time or temperature. Therefore, FFPE tissue sections are suitable for proteomic studies for at least 48 weeks from the time of sectioning.
Bridging the gap: access to health care and control of type 2 diabetes mellitus, hypertension and bronchial asthma among Egyptian women
Authors: Elmeshmeshy Eman Ibrahim , Abdelaziz Basma , Soliman Saeed
Published: February 2025

Background

Non-communicable diseases burden is rising globally; women are disproportionately affected by both non-communicable diseases burden and lack of access to health care. Research on the relationship between access to health care and non-communicable diseases control are limited. We aimed to assess the relationship between women’s access to health care and three non-communicable diseases control.

Methods

A cross-sectional study was conducted on 420 women diagnosed with diabetes mellitus, hypertension and/or Asthma. Access to health care was assessed through pretested validated Arabic version of access 31 questionnaire. The control status of diabetes mellitus, hypertension, and asthma was assessed according to the American Diabetes Association HbA1c targets, World Health Organization Guidelines, and the Global Initiative for Asthma control assessment tool, respectively. The associations were assessed using univariate and multivariate logistic regression analysis.

Results

(83%) of the participants had poor access to health care, of those, (39.0%) achieved non-communicable diseases control, while (16.9%) participants had good access to health care, of them, (83.1%) had their non-communicable diseases controlled. This difference in non-communicable diseases control proportions across access to care groups was statistically significant (P < 0.001). Women with good access to health care had higher odds (Adjusted Odds Ratio 6.33, 95% confidence interval: 3.24–12.55) of having their non-communicable diseases controlled compared with those with poor access.

Conclusion

Improving access to health care is essential for achieving better non-communicable diseases control.
Perceptions of ethical decision-making climate among clinicians working in European and US ICUs: differences between religious and non-religious healthcare professionals
Authors: Jensen Hanne Irene , Bülow Hans-Henrik , Dierickx Lucas , Vansteelandt Stijn , Vaschetto Rosanna , Élö Gábor , Piers Ruth , Benoit Dominique D.
Published: February 2025

Background

Making appropriate end-of-life decisions in the intensive care unit (ICU) requires shared interprofessional decision-making. Thus, a decision-making climate that values the contributions of all team members, addresses diverse opinions and seeks consensus among team members is necessary. Little is known about religion’s influence on ethical decision-making climates. Therefore, this study aimed to examine the association between religious belief and ethical decision-making climates.

Methods

The study was a cross-sectional analytical observation study as a part of the prospective observational DISPROPRICUS study. A total of 2,275 nurses and 717 physicians from 68 ICUs representing 12 countries in Europe and the US participated. All participants were asked which religion (if any) they belonged to and how important their religion (if any) was for their professional attitude towards end-of-life care. Perceptions of ethical decision-making climates were evaluated using a validated, 35-item self-assessment questionnaire that evaluates seven factors. Using cluster analysis, ICUs were categorised into four ethical decision-making climates: good, average (with nurses’ involvement at the end of life), average (without nurses’ involvement at the end of life) and poor.

Results

Of the 2,992 participants, 453 (15%) were religious (had religious convictions and found them important or very important for their attitude towards end-of-life care). The remaining 2,539 were non-religious (i.e. had religious convictions but assessed that they were not important for their attitude towards end-of-life care). When adjusting for country and ICU, the overall perception of the four ethical climates was associated with religious beliefs, with non-religious healthcare providers having more positive perceptions of the ethical climates compared to religious healthcare providers (p < 0.01). Within good climates, non-religious healthcare providers rated leadership by physicians (p < 0.01), interdisciplinary reflection (p = 0.049) and active decision-making by physicians (p = 0.02) as more positive compared to religious participants. In poor climates, religious healthcare providers had a more positive perception of the active involvement of nurses (p = 0.01). Within the other climates, no differences were found.

Conclusions

Overall perceptions of ethical decision-making climates were associated with religious beliefs, with non-religious healthcare providers generally having a more positive perception of the ethical climates than religious healthcare providers.
A qualitative analysis of unintended effects of a digital conditional cash transfer intervention to encourage healthcare utilization in Southern Madagascar
Authors: Franke Mara Anna , Neumann Anne , Nordmann Kim , Suleymanova Daniela , Ravololohanitra Onja Gabrielle , Knauss Samuel , Emmrich Julius Valentin
Published: February 2025

Introduction

Cash transfer interventions, including those using mobile money, are becoming increasingly widespread, particularly in Sub-Saharan Africa. As such interventions can have significant positive and negative unintended consequences, further analyses are needed to identify these consequences.

Methods

We investigated the unintended consequences of a digital conditional cash transfer intervention implemented at fifteen health facilities in Southern Madagascar. The intervention offered partial cost coverage for patients seeking care for potentially life-threatening conditions, accidents and injuries, maternal or pediatric care between February 2021 and June 2022. We conducted a qualitative analysis of in-depth interviews with policymakers, healthcare providers, (non-) beneficiaries of the intervention, and staff that implemented the intervention using reflexive thematic analysis.

Results

We identified three key positive and three key negative unintended consequences of the intervention. The key positive unintended consequences were: i) improved quality of care, ii) improved interpersonal relationships, including between patients and providers and between healthcare providers, and iii) digital skills development of healthcare providers and increased trust in mobile money. The three key negative consequences we identified were i) facility overcrowding, ii) an increase in costs of care, and iii) cases of hospital imprisonment.

Conclusions

Designers and implementers of future (digital) cash transfer interventions should carefully consider and proactively seek to leverage the positive and mitigate the negative unintended consequences of cash transfer interventions for healthcare such as those highlighted in our work.
Effects of nano-selenium and/or vitamin E supplementation on growth performance, antioxidant status, histopathology and resistance to Aspergillus flavus in Nile tilapia (Oreochromis niloticus)
Authors: Bazina Walaa K. , Tawfik Wesam A. , Abd Elghany Nadia A. , Saadony Saadea , Abdul Kari Zulhisyam , Alamoudi Muna Omer , Aly Mohamed Y. M. , Younis Abuelhassan Elshazly , Mathew Roshmon Thomas , Eissa Moaheda E. H. , Munir Mohammad Bodrul , Ibrahim Saadiah , Yousef Ismail , Omar Yusuf O. H. , Eissa El-Sayed Hemdan , Abd Elnabi Heba E.
Published: February 2025

Background

This study aimed to evaluate the effects of selenium nanoparticles (SeNPs) and/or vitamin E (VE) on the growth, body composition, metabolic parameters, histopathology, and resistance of Nile tilapia to Aspergillus flavus.

Results

Monosex Nile tilapia fingerlings were sourced from the Bazina farm and hatchery in Ismailia Governorate, Egypt, where the experiment was also conducted. The fish were acclimatized for 15 days before the trial. A total of 240 fingerlings (average weight 46 ± 3.0 g/fish) were divided equally across 12 concrete tanks (1 × 1 × 1.2 m, 1 m³ capacity), with 20 fish per tank. The fish were fed a control diet (T0), which was a basal diet with no supplementation, or one of three experimental diets for 60 days: T1 (1 mg SeNPs/kg), T2 (100 mg VE/kg), and T3 (1 mg SeNPs + 100 mg VE/kg). The experiment followed a completely randomized design (CRD) with three replicates per treatment. The combination of SeNPs and VE (T3) resulted in the best feed conversion ratio. A slight but significant increase (P < 0.05) in whole-body composition was observed in all treatment groups compared to the control. Biochemical parameters, serum digestive enzyme activity, and antioxidant levels improved significantly with dietary supplementation. Histopathological analysis revealed somewhat lacerated gill arches in fish fed SeNPs, VE, or their combination, but the overall gill structure remained normal. The SeNPs + VE group exhibited improved villi length and normal morphology of portal veins and hepatic sinusoids, though some vacuolated hepatocytes were noted. Fish in the SeNPs + VE group had the lowest mortality rates and the highest resistance to A. flavus.

Conclusion

Supplementing diets with SeNPs and/or VE enhances growth, body composition, biochemical parameters, and histopathology in Nile tilapia. The combination of 1 mg SeNPs + 100 mg VE/kg improves immune response and growth, offering a promising strategy to enhance Tilapia health and productivity.
Effects of increasing levels of rubber seed cake on growth performance, nutrient digestion metabolism, serum biochemical parameters, and rumen microbiota of Hu sheep
Authors: Zhao Huwei , Hua Jinling , Lu Wenwen , Yan Longfei , Zhang Min , Chen Chao , Lv Xiaokang
Published: February 2025

This study aimed to reveal the effects of increasing levels of rubber seed cake (RSC) on growth performance, nutrient digestion metabolism, serum biochemical parameters, and rumen microbiota in Hu sheep. In this study, 48 Hu sheep, weighing 17.01 ± 0.57 kg at 3 months of age, were randomly divided into four treatments: 0% rubber seed cake (RSC0%), 6% rubber seed cake (RSC6%), 12% rubber seed cake (RSC12%) and 18% rubber seed cake (RSC18%), with 12 sheep per group. Compared to the RSC0%, the ADG and DMI of the RSC6% and RSC12% were increased (P > 0.05). The apparent digestibility of OM and EE quadratically (P < 0.05) changed with the increase of RSC supplementation, with the greatest apparent digestibility of OM and EE observed in the RSC6% diet. With increased RSC supplementation, the N intake and fecal N increased linearly (P < 0.05), and the apparent digestibility of N reduced linearly (P < 0.05). As the increase of RSC supplementation, the serum levels of IgA, IgM, IgG, IL-4, T-AOC, and GSH-Px increased linearly (P < 0.05), and the serum level of IL-6 reduced linearly (P < 0.05). The serum level of IL-1β reduced quadratically (P < 0.05) with the increased RSC dose, and the serum level of SOD increased quadratically (P < 0.05) with the increased RSC dose. The ruminal NH3-N and the relative abundance of norank_Muribaculaceae quadratically (P < 0.05) changed with increased RSC supplementation, and the greatest relative abundance of norank_Muribaculaceae was observed in the RSC6% diet. In general, incorporating RSC into the diet of Hu sheep did not adversely affect growth performance and rumen fermentation characteristics. Supplementing with 6% RSC enhanced the relative abundance of norank_Muribaculacea in the rumen fluid and the immune and antioxidant capabilities. However, supplementing with 12 and 18% RSC might have negatively impacted nutrient digestion and metabolism. Therefore, this study recommended replacing corn and soybean meal with 6% RSC in the diet of Hu sheep.
Toward humanistic healthcare through dystopian visions: Sally Wiener Grotta’s “One Widow’s Healing”
Authors: Kang Meeyoung
Published: February 2025

Background

Critical medical humanities critique the traditional medical humanities’ focus on producing humane doctors, arguing that it plays only a supplementary role in medical education, and advocate for understanding health, disease, and humanity from a biocultural perspective. Essentially, they emphasize structural inequalities in modern medicine.

Methods

This study analyzes Sally Wiener Grotta’s “One Widow’s Healing” from the perspective of critical medical humanities. In line with this critical perspective, this study highlights the human alienation and oppression caused by biopower and technology-driven medicine in “One Widow’s Healing.”

Results

This story presents a dystopian vision of future healthcare systems in the highly technologically advanced and hyper-connected societies of 2100 and advocates for a reorientation of medicine toward a holistic, culturally informed practice that prioritizes human well-being and empathy.

Conclusions

By analyzing the literary response to the dystopian future, this study explores the potential dangers at the intersection of capitalism and technocentric healthcare, reflecting on the future direction of humanistic medicine.
Biomarkers to predict the outcomes of surgical intervention for aortic dissection
Authors: Hanna Abanob G. , Contreras Fabian Jimenez , Sharaf Omar M. , Stinson Griffin P. , Hess Philip J.
Published: February 2025

Purpose

Aortic dissections and repairs are associated with high rates of mortality. The aim of this review is to summarize the literature concerning the prognostic ability of various preoperative biomarkers for patients undergoing surgical repair of the thoracic and abdominal aorta to elucidate whether these biomarkers could improve the selection of surgical candidates.

Methods

Relevant biomarkers were selected if they had predictive value in inflammatory disease processes and/or cardiovascular disease. Full-text articles available in English on PubMed that related these biomarkers to the prognosis of aortic repair following aortic dissection were examined.

Results

For patients who underwent repair for type A dissection, a preoperative elevated SII was associated with inferior 30-day survival (hazard ratio: 3.532, 95% confidence interval: 1.719–7.255, p = 0.001) and increased rates of adverse cardiovascular events. Elevated preoperative IL-6 and D-dimer levels were independently associated with single-organ dysfunction, multiorgan dysfunction, and death. The use of a combination of markers was a stronger predictor. The areas under the curve (AUCs) for the specified IL-6 and D-dimer cutoff values were 0.901 and 0.817, respectively, whereas the AUC reached 0.936 when IL-6 was combined with D-dimer. For patients who underwent thoracic endovascular aortic repair (TEVAR) for type B dissection, an elevated postoperative systemic immune-inflammation index (SII) was an independent risk factor for aorta-related complications, graft failure, and significantly inferior freedom from aortic-related mortality. A combination of elevated preoperative and postoperative SII values was again predictive of in-hospital adverse outcomes and follow-up complications, including endoleaks, branch artery stenosis, distal aortic expansion, aortic rupture, and death (p = 0.0016). An elevated preoperative neutrophil‒leukocyte ratio (NLR) is associated with an increased incidence of early postoperative adverse events and poor survival.

Conclusions

Inflammatory markers seem to have predictive ability for postoperative outcomes after aortic repair in type A dissections. Further studies should compare these biomarkers to determine the best predictive marker for individual disease states and surgeries.