bluuebunny/crossref_metadata_2025 huggingface dataset:
Bispecific T-Cell Engagers for the Recruitment of T cells in Solid Tumors: A Literature Review
Authors: Dewaele Laura , Fernandes Ricardo
Published: January 2025

In the past decade, T-cell based immunotherapies have grown to become some of the most promising treatments for cancer. Following the success of immune checkpoint inhibitors, other T-cell based therapies emerged including CAR-T cells and bispecific T-cell engagers (BiTEs). BiTEs have the unique ability to crosslink T cells and tumor cells independently of MHC restriction. They do not rely on TCR specificity or the CD4+/CD8+ costimulatory molecules, overcoming tumor MHC downregulation and low-affinity TCR binding. However, like many other immunotherapies, BiTEs have shown limited success beyond the treatment of hematological malignancies. BiTEs for the treatment of solid tumors still face challenges. Studies in gastrointestinal tumors have revealed Fc toxicity, short half-lives, and immunotoxicity, leading to Fc-silenced half-life extended BiTEs with humanized single-chain variable fragments. Studies in prostate tumors, lung tumors, and malignant gliomas have identified promising targets in PSMA, DLL3, and EGFRvIII, respectively, but also highlighted the problems of on-target off-tumor and BiTE-specific toxicities and inaccessible and immunosuppressive tumor microenvironments. Ongoing research to overcome these limitations remains an interesting field to follow, as BiTEs have the potential to be a powerful tool, especially when used in combination with other immunotherapies.
Antibody ligation of HLA class II induces YAP nuclear localization and formation of cytoplasmic YAP condensates in human endothelial cells
Authors: Lone Moien , Anwar Tarique , Sinnett-Smith James , Jin Yi-Ping , Reed Elaine F , Rozengurt Enrique
Published: January 2025

Antibody (Ab) crosslinking of HLA class II (HLA II) molecules on the surface of endothelial cells (ECs) triggers proliferative and prosurvival intracellular signaling, which are implicated in promoting chronic Ab-mediated rejection (cAMR). Despite the importance of cAMR in transplant medicine, the mechanisms involved remain incompletely understood. Here, we examined the regulation of yes-associated protein (YAP) nuclear cytoplasmic localization and phosphorylation in human ECs challenged with Abs that bind HLA II, which are strongly associated with cAMR. To examine changes in YAP localization in response to Ab-mediated engagement of HLA II, we used an adenoviral vector to express the class II transactivator or treatment with interferon γ. In unstimulated ECs expressing HLA II, YAP localized mainly in the cytoplasm. Stimulation with HLA II Ab (0.1–1 µg/mL) induced marked translocation of YAP to the nucleus. HLA II signaling triggered by high concentrations of HLA II Ab (1 µg/mL) also induced prominent YAP localization in cytoplasmic punctate structures that were disassembled by exposure to 1,6-hexanediol, suggesting that these structures are biomolecular condensates. Using multiple treatments, including stimulation with serum, thrombin or HLA I Ab and conditions (eg ECs plated at different densities) indicate that formation of YAP cytoplasmic puncta can be dissociated from YAP nuclear localization and phosphorylation at Ser127, a site in YAP targeted by the Hippo kinases LATS1/2. The results revealed that HLA II signaling regulates YAP subcellular distributions in ECs and demonstrate, for the first time, that HLA II Ab selectively stimulates YAP concentration in punctate structures.
Distinct Cytokine Patterns Identify Acute and Convalescent Myocardial Involvement After Coronavirus Disease 2019: A Multicohort Biomarker Study
Authors: Zidar David A , McComsey Grace A , Anthony Donald D , McDaniel John , Chan Timothy A , Al-Kindi Sadeer G
Published: January 2025

We sought to identify the immunobiologic underpinnings of cardiac involvement as a postacute sequela of coronavirus disease 2019 (COVID-19) by comparing acute and convalescent populations. For the latter, an integrated analysis of cytokine levels, cardiac magnetic resonance imaging, and cardiopulmonary exercise capacity was performed. Unlike acute cardiac injury, which was associated with heightened tumor necrosis factor alpha (TNF-α) but not interleukin 18 (IL-18), convalescent myocardial inflammation/edema correlated with IL-18 but not TNF-α. Thus, inflammation is not a monolith in relation to cardiac involvement in the setting of COVID-19. Instead, convalescent cardiac involvement may emerge from mechanisms distinct from acute injury, and appropriately targeted therapies may prevent postacute sequalae of COVID-19.
Death in a Foreign Land: Turkish Muslim Exiles and the Making of Theodicy
Authors: Shively Kim
Published: January 2025

This article explores how Turkish Muslim migrants associated with the Gülen movement in the United States confront questions relating to death and burial in a foreign land. Customarily, diasporic Turks opt to repatriate to the homeland for burial. The followers of Fethullah Gülen, however, cannot easily return home because they are accused of masterminding the 2016 coup attempt in Turkey. The Turkish government thus views the movement as traitorous and deserving punishment, such that the movement members fear returning to Turkey, even to be buried. To make sense of their situation—to create a theodicy—movement members have drawn on Islamic history, ethical requirements, and philosophical traditions to reevaluate the eschatological implications of burial in a foreign land. The experience of exile has compelled them to reevaluate sacred history and rethink the promise of ultimate redemption in ways that foreground and valorize their unexpected expulsion from the homeland.
Endplate Remodeling: a key indicator of cigarette smoke exposure-induced intervertebral disc degeneration in a male rat model
Authors: Kelley Joshua , Li Hui , Sun Yi , Ren Pengling , Chen Guanghua , Sun Shuchun , Zhao Jichao , Buchweitz Nathan , Kern Michael , Reitman Charles A , Townsend Danyelle M , Yao Hai , Wu Yongren
Published: January 2025

Recent clinical studies have established a strong association between cigarette smoking and degenerative disc disease. Both in vitro and in vivo research indicated that cigarette smoke disrupts cellular homeostasis in the intervertebral disc (IVD), leading to spatiotemporal remodeling of the extracellular matrix, with a notable reduction in solute diffusivity within the cartilage endplate (CEP). As the CEP serves as a critical mechanical barrier and solute diffusion pathway for the IVD, both roles can be compromised by pathological changes in the tissue. This underscores the need for a more comprehensive examination of endplate remodeling during IVD degeneration, particularly in the context of cigarette smoking and cessation. The objective of this study was to perform a quantitative analysis of the structure-material property relationship changes in the endplate at tissue and cellular levels to determine how endplate mineralization progresses during IVD degeneration in the context of cigarette smoke exposure and cessation, using our previously developed Sprague–Dawley rat model. Our results indicates that cigarette smoke exposure induced endplate remodeling is characterized by a higher CEP histological grade, increased aberrant CEP calcification level, and elevated bony endplate surface flatness score, all of which correlated with an accelerated chondrocyte cell life cycle. Smoke cessation alone was insufficient to reverse the mineralization progression in the endplate. Principal component analysis further identified alterations in endplate morphometry at the tissue level and disruptions in the chondrocyte life cycle at cellular level as key markers of degenerative remodeling. These findings establish endplate remodeling as a key indicator of smoke exposure induced IVD degeneration and inform the development of novel therapeutic strategies aimed at preserving or improving disc health.
What Do You Do Outside of Work? When and Why Disclosing Eudaimonic Leisure Activities Increases Competence Perceptions and Consumer Choice
Authors: Daniels Michelle E , Samper Adriana , Morales Andrea C
Published: January 2025

Consumers have increasing access to more holistic information about the providers they consider working with and hiring (e.g., realtors, designers), including how they spend their free time. This research examines how a professional’s disclosure of their leisure activities impacts consumer choice. While the way people spend their leisure time should be unrelated to their professional aptitude, across an online field study and four lab studies, the authors demonstrate that disclosing leisure activities associated with eudaimonic well-being (ie, meaning, fulfillment), such as hiking or cooking, can positively impact consumer choice. Such disclosures, relative to either not disclosing leisure or disclosing less eudaimonic activities such as relaxing or watching television, increase perceptions of competence, and in turn, interest in choosing, hiring, and supporting these individuals. Notably, the effects of eudaimonic leisure on competence and hiring intentions are attenuated if other diagnostic competence cues are present, such as a job- related award, and among those who value productivity less (ie, have a low productivity orientation). Thus, the authors show how seemingly irrelevant personal information about professionals can inform consumer choice. Moreover, by manipulating eudaimonic well-being via leisure disclosures, they demonstrate how such cues impact person perception, integrating research on well-being, self-disclosure, and social perceptions.
Pipsan Saarinen Swanson’s Life Model Home: Mediation and Mythmaking in Postwar America
Authors: Kowalski Alison
Published: January 2025

In a 1955 photographic essay, Life magazine published model interiors designed by Pipsan Saarinen Swanson, telling its readers they represented an authentic regional style called “Nordic Modern of the Midwest.” In this paper, I conduct a close visual and textual reading of the magazine spread as well as other archival documents related to Swanson’s model home. This reading I contextualize within design and cultural histories to demonstrate that Life framed the model home to suit its own agendas to, on the one hand, celebrate American culture and, on the other hand, promote modern design. I argue that in so doing, the magazine presented Swanson’s work in a manner that bolstered and expounded on a myth that had recently been circulating the design world in the United States. Promulgated by historians, writers, and designers, this myth revised the established history of modern design to relocate its origins from early twentieth-century Europe to pre-1900 America.
Frailty and outcomes in adults undergoing systemic anti-cancer treatment: a systematic review and meta-analysis
Authors: Pearce Jessica , Martin Sally , Heritage Sophie , Khoury Emma G , Kucharczak Joanna , Nuamek Thitikorn , Cairns David A , Velikova Galina , Richards Suzanne H , Clegg Andrew , Gilbert Alexandra
Published: January 2025

Background

It is increasingly recognised that frailty should be assessed and considered in treatment decision-making in patients with cancer. This review and meta-analysis synthesises existing evidence evaluating the association between baseline frailty and Systemic Anti-Cancer Treatment (SACT) outcomes in adults with cancer.

Methods

Five databases were systematically searched from database inception to January 2023 to identify prognostic factor studies (cohort/case-control design) reporting the associations between validated frailty assessments (pre-treatment) and follow-up outcomes in adults with solid-organ malignancy undergoing SACT. Risk of bias (RoB) was assessed via Quality of Prognosis Studies in Systematic Reviews tool. Where appropriate, associations between frailty and outcomes (survival, toxicity, treatment tolerance, functional decline/quality of life and hospitalisation) were synthesised in meta-analysis and presented as forest plots.

Results

58 studies met inclusion criteria. They were undertaken in a range of tumour sites and mainly in older patients and advanced disease/palliative settings. Most had low/moderate RoB. Nine frailty assessment tools were evaluated. Four outcomes were synthesised in meta-analysis, which demonstrated the prognostic value of two tools: Geriatric-8 (G8; survival, treatment tolerance, hospitalisation) and Vulnerable Elders Survey-13 (VES13; survival, toxicity, treatment tolerance). Overall pooled estimates indicate that frailty conveys an increased risk of mortality (hazard ratio (HR) 1.68, 95% confidence interval 1.41-2.00), toxicity (odds ratio (OR) 1.83, 1.24-2.68), treatment intolerance (OR 1.68, 1.32-2.12) and hospitalisation (OR 1.94, 1.32-2.83).

Conclusion

Simple, brief frailty assessments including G8 and VES13 are prognostic for a range of important outcomes in patients undergoing SACT. Risk estimates should be used to support shared decision-making.
Building a Culture of Health Through Leader-Inspired Nutrition
Authors: Currie Tanisha L , Crawford Cindy C , Scott Jonathan M , Troncoso Melissa R , McCarthy Mary S , Lindsey Andrea T , Deuster Patricia A
Published: January 2025

The balance of operational readiness and maintaining a healthy recruitment force presents increasing challenges within the DoD. Chronic preventable diseases, such as overweight and obesity, along with musculoskeletal injuries, are threats to recruitment and retention. Novel approaches are needed and leaders are in a unique position to serve a key role in influencing nutrition readiness. Leader-Inspired Nutrition (LIN) is a proposed framework that equips leaders with strategies for building a culture of health. Leader-Inspired Nutrition provides an approach leaders can leverage within units to improve health and performance. The LIN framework was developed from relevant and evidence-based information through collaboration with key nutrition subject matter experts and leaders. The 7 core pillars of LIN are to integrate nutrition basics, model top-down nutrition behaviors, promote a performance-focused food environment, integrate dietary supplements knowledge, consider economic factors that affect nutrition choices, evaluate Total Force Fitness impact, and promote utilization of DoD wellness resources. Each pillar provides leaders with a practical approach to engaging service members while encouraging nutrition readiness. As leaders engender trust and serve as role models, the adoption of the LIN framework in their units can guide and foster a culture of health within the DoD. Leader-Inspired Nutrition will assist leaders in building shared communities through healthful nutrition and mealtime experiences and serve to shape military nutrition policies that affect readiness within the DoD. This commentary describes the concept of LIN, the elements and principles of LIN, and how leaders can inspire service members to maximize performance to support nutrition readiness.
The Association Between Disordered Eating and Musculoskeletal Injury Among Marine Officers Upon Entry to the Basic School
Authors: Exley Lt Shannon L , Schvey Natasha A , Ricker Emily , Raiciulescu Sorana , Barrett Amelia S , de la Motte Sarah J
Published: January 2025

Introduction

Active duty service members (ADSMs) may be at heightened risk for eating disorders (EDs) and sub-clinical disordered eating (DE). ADSMs are also at a high risk for musculoskeletal injury (MSK-I). Given the risk for EDs/DE among ADSMs as well as robust physical requirements of military training, additional research is needed to elucidate links between DE and risk for MSK-I among ADSMs. The aim of the present study was to assess the prevalence of DE and associations with MSK-I among Marine Corps officers entering a 6 month leadership course.

Materials and Methods

The current cross-sectional study is part of a large, prospective study, the Initiation of Marine Physiological Assessment of Combat Training (IMPACT) study. Participants completed the Eating Disorder Examination-Questionnaire Short (EDE-QS) and self-reported the presence of a recent (≤6 months) MSK-I upon entry to an officer training course. A logistic regression was used to assess the association between elevated DE (EDE-QS ≥15) and recent MSK-I, adjusting for age, race, sex, and commissioning source.

Results

N = 1,382 officers (11.6% female, MAge: 24.8 ± 2.9 years, 26.6% racial/ethnic minority) completed the questionnaires. Seven percent had elevated DE (EDE-QS score ≥15) (female: 10.6%, male: 6.9%, P = .10); 18.3% self-reported recent MSK-I (female: 26.3%, male: 17.3%; P = .009). Females had 17% greater odds of MSK-I compared to males (aOR: 1.17, 95% CI: 1.03-1.33, P = .02). Moreover, females with elevated DE had greater odds of MSK-I than males with elevated DE (aOR= 1.38); among females, odds of MSK-I were greatest among those with elevated DE (aOR= 1.35).

Conclusions

In this sample of Marine officers, DE was associated with greater odds of a recent MSK-I among women only. Results align with previously reported relationships between DE and skeletal health in female athletes. Prospective research is needed to elucidate the temporal nature of these relationships.
scHiGex: predicting single-cell gene expression based on single-cell Hi-C data
Authors: Shrestha Bishal , Siciliano Andrew Jordan , Zhu Hao , Liu Tong , Wang Zheng
Published: January 2025

A novel biochemistry experiment named HiRES has been developed to capture both the chromosomal conformations and gene expression levels of individual single cells simultaneously. Nevertheless, when compared to the extensive volume of single-cell Hi-C data generated from individual cells, the number of datasets produced from this experiment remains limited in the scientific community. Hence, there is a requirement for a computational tool that can forecast the levels of gene expression in individual cells using single-cell Hi-C data from the same cells. We trained a graph transformer called scHiGex that accurately and effectively predicts gene expression levels based on single-cell Hi-C data. We conducted a benchmark of scHiGex that demonstrated notable performance on the predictions with an average absolute error of 0.07. Furthermore, the predicted levels of gene expression led to precise categorizations (adjusted Rand index score 1) of cells into distinct cell types, demonstrating that our model effectively captured the heterogeneity between individual cell types. scHiGex is freely available at https://github.com/zwang-bioinformatics/scHiGex.
Chatbot Democracy
Authors: Croce Nicholas
Published: January 2025

What will be the role of chatbots in 21st century democratic processes? Considering the potential implementations of artificial intelligence (AI) “chatbots” or large language models (LLMs) with a natural language processing (NLP) interface for use in public administration, policy-making, and deliberative democratic processes, this essay explores representative and access-boosting roles for such chatbots: how they could supplement constituent services, increase access to government programs, facilitate deliberation, and perhaps even act as posthuman representatives within a deliberative democratic process. The essay reviews the burgeoning, multi-disciplinary academic literature dealing with the use of chatbots in both government and deliberative contexts—literature that probes questions of utility, representational ethics, equity and access. The essay concludes with an itinerary for further thinking and research, emphasizing the importance of both impact and formative evaluation.
Invalid exercises of powers and defective changes of trustees: what can go wrong and how to put it right
Authors: Pursall Tony
Published: January 2025

The first part of this article outlines some of the reasons why the exercise of powers can be invalid, with a focus on the failure to comply with formal requirements. The second part considers possible remedies, including the implied exercise of powers doctrine and the defective exercise of powers doctrine, as well as those available to the court where there has been a defective change of trustees. It argues that there will often be an available remedy that enables the invalid exercise of dispositive powers to be retrospectively validated even where the court does not have that jurisdiction.
Longitudinal Reliability of Milestones Learning Trajectories during Anesthesiology Residency
Authors: Sun Ting , Park Yoon Soo , Chen Fei , Hogan Sean O. , Tanaka Pedro
Published: January 2025

Background:

Longitudinal Milestones data reported to the Accreditation Council for Graduate Medical Education (ACGME) provide a structured framework for assessing the developmental progression of residents in key competencies and subcompetencies. This study aims to investigate the previously underexplored longitudinal reliability of Milestones data, with the goal of identifying patterns in learning trajectories that can inform targeted interventions for residents and programs.

Methods:

We conducted a retrospective cohort study with national anesthesiology Milestones data collected from 2014 to 2020. Mixed-effects growth curve models were fit to model residents’ growth trajectories. Longitudinal reliability was assessed using the indices of growth rate reliability (GRR) and growth curve reliability (GCR). We also examined variance components attributable to the factors at both the learner and program levels. Latent class growth analyses (LCGA) were performed to identify latent groups of learners with different learning trajectories.

Results:

The study included a total of 682,475 ratings for 4976 learners in 140 programs. Growth curve model results indicated that the mean baseline Milestone rating across the 25 subcompetencies was 2.05 (95% CI: 1.96-2.14), with an average increase of 0.49 (95% CI: 0.48-0.51) units per reporting period. The GRR (mean ± SD, 0.58 ± 0.03) suggested a moderate capability of anesthesiology Milestones to detect individual differences in the growth of latent competency. GCR estimates (mean ± SD, 0.76 ± 0.02) suggested acceptable overall reliability of Milestones across all the six assessment points. Significant variability was observed at both the program and learner levels (P < 0.001). LCGA identified 3-4 latent groups of learners with distinct learning trajectories across the 25 subcompetencies.

Conclusions:

Our study indicated that the anesthesiology Milestones provides moderately reliable information for tracking individual progress over time. The findings underscore the importance of using a multi-faceted approach to assessment and providing individualized learning plans to support resident development.
Conservative Reconstruction of the Lower Limb with a Bilayer Porous Collagen Matrix after a Spider Bite
Authors: Palmesano Marco , Bottini Davide Johan , Storti Gabriele , Secondi Lorenzo , Cossi Carlo , Calicchia Alessio , Giacalone Martina , Nunziata Irene , Basile Emanuela , Cervelli Valerio
Published: January 2025

Brown recluse spider bites may cause symptoms ranging from local cutaneous reactions to systemic visceral loxoscelism. Most bites are self-limiting, but some can lead to necrotic ulcerations with severe complications and soft tissue defects. Necrotizing ulcers are uncommon and have various clinical presentations, so no standard treatment exists. A 68-year-old man required medical attention after getting a spider bite while traveling in Tanzania. After returning to Italy, the patient presented with a posterior lower limb black papule, local edema, and fever. The lesion quickly ulcerated with an eschar. Medical history and symptoms suggested a brown recluse spider bite. Ulcer management was conservative, with careful surgical debridement and a two-step reconstruction using a split-thickness skin graft and a bilayer porous collagen matrix. Treatment resulted in functional recovery and acceptable aesthetics.
Evaluating a Hearing Loop Implementation for Live Orchestral Music
Authors: McWeeny Sean , Trainor Laurel J. , Armstrong Steve , Bosnyak Dan , Tawfik Hany , Bruce Ian C.
Published: January 2025

Objectives:

Live music creates a sense of connectedness in older adults, which can help alleviate the social isolation frequently associated with hearing loss and aging. However, most hearing-aid (HA) users are dissatisfied with the sound quality of live music and rate sound quality as important to them. Assistive listening systems are frequently independent of a user’s HAs and fall short in tailoring to each individual’s hearing loss. The present study thus tested whether the use of a hearing loop would improve sound quality during an orchestral concert.

Design:

Participants with symmetrical moderate-to-severe hearing loss were assigned to use Sonova-provided HAs with a telecoil (n = 20) or their own HAs (n = 8) without a telecoil during a performance by the Hamilton Philharmonic Orchestra. We changed loop input to use one of three feeds every 5 minutes: a mix of microphones from the hall’s standard assistive feed on the first balcony (house condition), a mix of microphones located on the stage (stage condition), or no input to the loop (no feed). After each 5-minute interval, we collected sound quality and naturalness ratings for the previous 5 minutes.

Results:

Sound quality and naturalness ratings were highly related (rRM = 0.81), though each provided unique insight. Repeated measures analysis of variance found significant differences among the loop feed conditions for sound quality and naturalness, with the no feed condition significantly outperforming the house condition on sound quality [t(18) = −3.73, adj. p = 0.005] and naturalness [t(18) = −4.15, adj. p = 0.002]. Mixed effects models allowed us to retain the richness of a repeated observation dataset and provided point estimates of the overall quality and naturalness among conditions; however, assumption violations of normality and homoskedasticity prevented further interpretation.

Conclusions:

Though HA-integrated assistive listening systems are a promising option for improving live music for people with hearing loss, a hearing loop does not seem to be crucial for orchestral music. Future directions include improving lyric understanding for music with vocals and customizing user experience via Bluetooth Low Energy Audio systems.
Recent advances in pharmacological treatments of proliferative vitreoretinopathy
Authors: Sanchez-Suarez Jeysson , Kim Yoon Jeon , Miller William P. , Kim Leo A.
Published: January 2025

Purpose of review

Proliferative vitreoretinopathy (PVR) is a severe complication of retinal detachment and trauma, posing significant challenges to surgical success and visual prognosis. Despite advancements in vitreoretinal surgery, PVR incidence remains unchanged, this review presents a synthesis of the principal clinical and preclinical research findings from recent years.

Recent findings

Recent research has focused on anti-inflammatory, antiproliferative, and antifibrotic agents. Corticosteroids, such as triamcinolone and dexamethasone, show promise in reducing inflammation but have inconsistent results. Methotrexate and mitomycin C demonstrate efficacy in preclinical and select clinical scenarios. Anti-vascular endothelial growth factor agents and immunotherapies, like infliximab, have shown limited clinical benefits despite promising preclinical data. Novel approaches, including CB2 receptor agonists, exosome-based drug delivery, and nuclear factor kappa B pathway inhibitors, are gaining traction. Additionally, RNA-based and multitargeted therapies highlight the importance of addressing inflammation, fibrosis, and proliferation simultaneously.

Effective management of PVR requires multifaceted therapies targeting its complex pathogenesis. While current treatments are limited, ongoing research in precision drug delivery and combination therapies offers hope for improved outcomes. Future strategies should focus on translating promising preclinical findings into robust clinical applications.
Real‑world therapeutic strategies and survival outcomes in advanced HER2-mutant non-small cell lung cancer
Authors: Sun Ruei-Lin , Liao Pei-Ya , Liao Ying-Ting , Yeh Yi-Chen , Chiang Chi-Lu , Chen Yuh-Min , Hsu Kuo-Hsuan , Tseng Jeng-Sen , Huang Hsu-Ching , Shen Chia-I , Tseng Yen-Han , Huang Yen-Hsiang , Luo Yung-Hung , Yang Tsung-Ying
Published: January 2025

Background:

Limited information is available regarding the clinical features and outcomes of advanced human epidermal growth factor receptor 2 (HER2)-mutant non–small cell lung cancer (NSCLC) in Taiwan, despite expanding treatment options for this distinct subtype. The present study explored the clinical features and outcomes of HER2-mutant NSCLC in a real-world setting.

Methods:

Relevant data were collected from patients with advanced or recurrent HER2-mutant NSCLC who received systemic therapy between 2011 and 2021 and were followed up until 2022 at two medical centers in Taiwan. Clinical features, treatment responses, and survival-associated factors were analyzed.

Results:

This study included 45 patients (median age: 59.7 [range: 41.3–78.7] years). A775_G776insYVMA was the most common NSCLC subtype (57.8%), followed by G778_P780dup (11.1%). Approximately 53.3% of the patients received first-line platinum-based chemotherapy (PC) alone, whereas 13.3% received PC combined with an immune checkpoint inhibitor (ICI). The median overall survival (OS) and progression-free survival (PFS) after first-line therapy were 25.8 and 4.4 months, respectively. The objective response rate was generally higher in patients receiving first-line PC + ICI than in those receiving PC alone (33.3% vs. 12.5%; p = 0.269). Furthermore, patients receiving PC + ICI had longer PFS than did those receiving PC alone (9.5 vs. 4.4 months; p = 0.131) and those receiving tyrosine kinase inhibitor/ICI monotherapy (9.5 vs. 0.5 months; p = 0.015). Compared with patients having other NSCLC subtypes, those carrying HER2 exon 20 insertion mutations had shorter median PFS (17.3 vs. 2.9 months; p = 0.043) and OS (not reached vs. 19 months; p = 0.031).

Conclusion:

This study highlights the clinical features and outcomes of advanced HER2-mutant NSCLC in Taiwan. PC + ICI may be more effective than other regimens as first-line therapy. The prognostic role of HER2 exon 20 insertion mutations warrants further investigation.
Deciphering the impact of dietary habits and behavioral patterns on colorectal cancer
Authors: Yuan Qihang , Liu Jiahua , Wang Xinyu , Du Chunchun , Zhang Yao , Lin Lin , Wang Chengfang , Hong Zhijun
Published: January 2025

Colorectal cancer (CRC) is a malignant tumor that originates from the epithelial cells of the colon and rectum. Global epidemiological data shows that in 2020, the incidence and mortality rate of CRC ranked third and second, respectively, posing a serious threat to people’s health and lives. The factors influencing CRC are numerous and can be broadly categorized as modifiable and non-modifiable based on whether they can be managed or intervened upon. Non-modifiable factors include age, gender, family history, among others. Among the modifiable factors, dietary habits and behavioral practices are the main intervention measures that people can take to prevent CRC. Numerous studies indicate that a high intake of red and processed meats, fats, as well as habits such as smoking, alcohol consumption, and prolonged sitting, increase the risk of developing CRC. Conversely, consuming ample vegetables, fruits, high dietary fiber, and engaging in moderate regular exercise may reduce the risk of CRC. This article primarily discusses the impact of dietary habits and behavioral practices on the occurrence and development of CRC, along with possible mechanisms, laying the foundation and providing direction for the prevention and control of CRC occurrence and development.
Frailty in kidney transplant candidates: new therapeutic strategies to intervene
Authors: Kirkman Danielle L.
Published: January 2025

Purpose of review

Patients that present with a physical frail phenotype have a higher risk of poor kidney transplant outcomes and are therefore less likely to be wait listed for a transplant. The physical frailty phonotype is more prevalent in older adults >65years with chronic and end stage kidney disease, thus partly contributing to inequitable access to transplant. Frailty can potentially be reversed by prehabilitation.

Recent findings

Small studies of prehabilitation in kidney transplant candidates have demonstrated feasibility and safety. These pilot studies have shown efficacy for improving functional surrogates of frailty. Encouraging findings from one small pilot study reported a 50% reduction in postoperative length of hospital stay in patients that participated in prehabilitation. Exercise intervention should be supported with nutrition intervention aimed at increasing energy intake. Lifestyle behavior change coaching and case-by-case clinical psychology support are a key for successful uptake of prehabilitation and sustainable lifestyle change.

There is consensus from the American Society of Transplantation, the European Society of Transplantation, and healthcare providers that prehabilitation is a valuable peri-operative intervention. Robust, multicenter randomized controlled trials will facilitate the establishment of evidence-based guidelines and widespread implementation of prehabilitation into clinical care.
Botulinum toxin injections for the treatment of hip instability in the pediatric population with cerebral palsy: a systematic review
Authors: Sala Debra A. , del Rosario Eduardo
Published: January 2025

The purpose of this review was to examine the effects of hip muscle botulinum toxin injections for the treatment of hip instability reported in studies of children with cerebral palsy. Searches in PubMed, CINAHL, and Web of Science were performed using the term hips combined with botulinum toxin and its various abbreviations and brand names. Reference lists and citations of the reviewed studies were also searched. Nine studies were reviewed: two randomized controlled trials plus a subsequent long-term follow-up of one of them, and six nonrandomized studies of interventions with two including comparison group(s) and four being single group pre–post studies. Hip adductors were injected in all studies with other hip muscles added in most cases. The outcome measure analyzed was the change in migration percentage defined as postinjection minus preinjection migration percentage with the recommendation of a change of ±10% indicating a true change. Only two studies reported a change exceeding this criterion. One randomized controlled trial demonstrated a 10.4% improvement in the botulinum toxin-treated group, which was statistically significantly greater than a 2.95% worsening in the comparison group. Additionally, a preliminary study of five participants found a statistically significant median change of ≥10% at two of the eight follow-up time points. Therefore, the results of most studies showed neither postinjection improvement nor worsening of this magnitude. The low level of rigorousness of the reviewed studies suggests that any of the results should be viewed cautiously.
Testosterone-induced Seminal Vesicle–like Differentiation in Cervical Mesonephric Duct Remnants in a Female to Male Transgender Patient
Authors: Ratnayake Gayanie , Talia Karen L. , Volchek Mila , McCluggage W. Glenn
Published: January 2025

Pure ductal-type mesonephric remnants in the uterine cervix are rare. We report an unusual case in a 31-yr-old of cervical mesonephric remnants of predominantly ductal type exhibiting seminal vesicle–like differentiation in a female-to-male transgender patient receiving long-term testosterone therapy. To the best of our knowledge, this phenomenon has not been previously reported. The impact of testosterone on the female genital tract is likely to be encountered more frequently due to increasing rates of gender-affirming surgery, including long-term androgen use. Awareness of the morphologic features is important as such changes may be misinterpreted as premalignant or malignant lesions. In reporting this unusual case, we briefly review lesions derived from cervical mesonephric remnants and testosterone-associated changes in the female genital tract.
TP53 Mutations and PD-L1 Amplification in Vulvar Adenocarcinoma of the Intestinal Type: Insights From Whole Exome Sequencing of 2 Cases
Authors: Fujii Erisa , Kato Mayumi Kobayashi , Ono Hanako , Yamaguchi Maiko , Higuchi Daiki , Koyama Takafumi , Komatsu Masaaki , Hamamoto Ryuji , Ishikawa Mitsuya , Kato Tomoyasu , Kohno Takashi , Shiraishi Kouya , Yoshida Hiroshi
Published: January 2025

Vulvar adenocarcinoma of the intestinal type (VAIt) is a rare subtype of primary vulvar carcinoma, with ∼30 cases documented in the English literature. This study presents 2 new cases of HPV-independent VAIt with lymph node metastasis and discusses their clinical presentation, histopathologic features, and whole exome sequencing (WES) analysis. Both cases exhibited histologic features consistent with VAIt, including tubular, papillary, and mucinous carcinoma components. Immunohistochemical analysis showed p16 patchy staining, CDX2, CK20, and SATB2 positivity, while being negative for ER, PAX8, and CK7. WES revealed pathogenic TP53 mutations in both cases, accompanied by distinct additional mutations (GRIN2A and KDM6A in Case #1; CHD4 in Case #2). Common copy number alterations (CNAs) included TP53 loss of heterozygosity and CD274/PD-L1 amplification. However, other CNAs varied between the cases. Immunohistochemistry for p53 suggests the presence of both wild-type and mutant subclones, indicating that TP53 abnormalities may be acquired during tumor progression. Both tumors showed mutational signatures SBS1 and SBS5, associated with aging and DNA damage. Our findings deepen the understanding of the genetic events involved in the tumorigenesis of HPV-independent VAIt. Given the TP53 abnormalities and CD274/PD-L1 amplification, emerging p53-based therapies and immune checkpoint inhibitors may represent potential treatment targets. While these findings contribute to the understanding of VAIt tumorigenesis, further research is required to validate these observations in a larger cohort.
Competency Gaps Among Governmental Public Health Employees With and Without a Formal Public Health Degree: Where Are We Now?
Authors: Gee MaKenzie , Taylor Heather , Yeager Valerie A.
Published: January 2025

Objective:

The purpose of this study is to examine whether differences in self-reported core competency skill gaps among U.S. governmental public health workers with and without a formal degree in public health have changed since the last assessment in 2017.

Design:

This cross-sectional study utilizes data from the 2021 Public Health Workforce Interests and Needs Survey (PH WINS). Bivariate relationships were analyzed by conducting chi-square tests of respondents’ supervisory level and reported skill gaps. Multivariate logistic regressions of reported skill gaps were performed holding gender, age, race/ethnicity, public health certificate attainment, role type, current employer, and tenure in public health practice constant.

Setting:

A nationally representative sample of U.S. government public health employees.

Participants:

36,752 U.S. governmental public health employees across local and state health agencies representing 47 states.

Main Outcome Measures:

Self-reported competency skills gaps.

Results:

In 2021, among both nonsupervisors and supervisors, having a formal public health degree (bachelors, masters, or doctorate) was significantly associated with reduced odds of reporting a skill gap across more than half of the competency skills assessed (14 of 23 skills and 17 of 24 skills, respectively). Nonsupervisors and supervisors with a formal public health degree had fewer skill gaps in 2021 than in 2017. Furthermore, whereas in 2017, when having a public health degree had no effect on executives reporting a skill gap, in 2021, having a public health degree was significantly associated with reduced odds of reporting 2 skill gaps.

Conclusions:

Overall, across all position levels (ie, nonsupervisory, supervisor, executive), public health workers with a public health degree experienced fewer competency skill gaps in 2021 than in 2017. These findings from PHWINS 2021 illustrate that formal public health education generally decreases competency gaps across numerous competency domains. However, the variability in reported gaps across supervisory levels shows the need for ongoing evaluation and adaptation of formal public health degree programs.
Regulatory Immune Cell-derived Exosomes: Modes of Action and Therapeutic Potential in Transplantation
Authors: Avalos-de Leon Cindy G. , Thomson Angus W.
Published: January 2025

Reduced dependence on antirejection agents, improved long-term allograft survival, and induction of operational tolerance remain major unmet needs in organ transplantation due to the limitations of current immunosuppressive therapies. To address this challenge, investigators are exploring the therapeutic potential of adoptively transferred host- or donor-derived regulatory immune cells. Extracellular vesicles of endosomal origin (exosomes) secreted by these cells seem to be important contributors to their immunoregulatory properties. Twenty years ago, it was first reported that donor-derived exosomes could extend the survival of transplanted organs in rodents. Recent studies have revealed that regulatory immune cells, such as regulatory myeloid cells (dendritic cells, macrophages, or myeloid-derived suppressor cells), regulatory T cells, or mesenchymal stem/stromal cells can suppress graft rejection via exosomes that express a cargo of immunosuppressive molecules. These include cell surface molecules that interact with adaptive immune cell receptors, immunoregulatory enzymes, and micro- and long noncoding RNAs that can regulate inflammatory gene expression via posttranscriptional changes and promote tolerance through promotion of regulatory T cells. This overview analyzes the diverse molecules and mechanisms that enable regulatory immune cell-derived exosomes to modulate alloimmunity and promote experimental transplant tolerance. We also discuss the potential benefits and limitations of their application as therapeutic entities in organ transplantation.
Detection and Genetic Characterization of Human Bocavirus 1 infection; Evolutionary Insights, in Western Province Sri Lanka
Authors: Fernando Tharushi Nawodhya , Arachchige Nipuni , Weerathunga Achini , Bowatte Asanga , Perera Shanika , Rathnayake Dinithi , Sumathipala Saranga , Dayananda Dilakshini , Muthugala Rohitha
Published: January 2025

Human bocavirus-1 (HBoV1) is a respiratory virus linked to various respiratory illnesses, but its prevalence and role in acute respiratory infections in Sri Lanka is not well investigated. This study investigated the prevalence of HBoV1 in respiratory samples from individuals suspected of having respiratory tract infections in the Western Province, Sri Lanka.
Two hundred systematically selected nasopharyngeal swab samples from suspected COVID-19 patients from January 2022 to May 2022 with acute respiratory tract infection (ARTI) symptoms from total of 1507 samples were included. Polymerase chain reaction (PCR) was performed to amplify the Nonstructural protein 1(NP1) gene region of HBoV. The positive sample was subjected to complete genomic sequence by using the Illumina sequencing platform.
HBoV was detected in one sample from a nine-month-old infant who presented with cough, fever, and sore throat. This sample was negative for other respiratory viruses and atypical bacteria. The sequence was aligned with reference sequences available in GenBank, which confirmed that the sample belongs to the HBoV1 genotype, with a nucleotide identity of 99.14%.
This study was able to detect HBoV1 infections in a patient with acute respiratory tract infection (ARTI) as a sole pathogen and genomic characterization of the isolate. This detection in a symptomatic infant highlights the importance of comprehensive respiratory pathogen testing.
Effector genes of type III secretion system and biofilm formation in virulent Pseudomonas aeruginosa isolates carrying bla
KPC-2 and bla
PDC-5 genes in hospital environment
Authors: de Almeida Vitelhe Ferreira , Urzêdo Jane Eire , Velikkakam Teresiama , Alves Moreira Gabriela Pires Cardoso , da Fonseca Sara Carolline Ribeiro , Bastos Clara Mariano , Royer Sabrina , Dias Vinicius Lopes , Almeida Junior Elias Rodrigues de , Martins Aires Caio Augusto , Maciel Maria Amélia Vieira , Ferro Cavalcanti Isabella Macário , Gontijo-Filho Paulo P , Ribas Rosineide Marques
Published: January 2025

Introduction. In critically ill patients, the occurrence of multidrug-resistant Pseudomonas aeruginosa infection is a significant concern, given its ability to acquire multidrug-resistant, form biofilms and secrete toxic effectors.

Hypothesis or Gap Statement. In Brazil, limited data are available regarding the prevalence of dissemination, and the impact of the type III secretion system (T3SS) on toxin production and biofilm formation in clinical isolates of P. aeruginosa.

Aim. This study investigates the dissemination of virulent P. aeruginosa harbouring the bla
KPC-2 and bla
PDC-5 genes, the presence of T3SS genes and their biofilm-forming capability.

Methodology. A total of 128 non-duplicate clinical isolates of carbapenem-resistant P. aeruginosa (CRPA) from different sources collected from eight hospitals were examined. Detection was performed by PCR of the T3SS genes (exoU, exoT, exoS and exoY), carbapenemases (bla
KPC, bla
GIM and bla
NDM) and beta-lactamase gene (bla
PDC). PFGE and phenotypic biofilm production (initial adhesion assay and biofilm cell concentration) were performed.

Results. We found exoT+ (86%) to be the most frequent genotypic variant, followed by exoY+ (61%). Notably, a substantial proportion of isolates exhibited the simultaneous presence of exoU+ and exoS+ genes, along with a high prevalence of bla
KPC-2
+ (64%) and bla
PDC-5
+ (64%) among the disseminated clones in the evaluated region. Additionally, 78% of the isolates demonstrated biofilm-forming capability, and two distinct clonal profiles were identified and disseminated both intra- and inter-hospital. Also, it was revealed that the exoU genotype was significantly more frequent among multidrug-resistant strains.

Conclusion. These findings underscore the ability of multiple virulent and biofilm-producing clones of CRPA to propagate effectively.