bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the recovery effects of antibiotic-resistant Lactiplantibacillus plantarum subsp. plantarum ATCC14917 on the antibiotic-disturbed intestinal microbiota using a mice model
Authors: Wang Yiwei , Wang Bini , Huo Zhenquan , Zhang Fuxin , Liu Yufang
Published: January 2025

Aims

Supplementing Lactobacillus alongside antibiotic treatment was a curative strategy to modulate gut microbiota and alleviate antibiotic-associated dysbiosis. But the lactobacilli that are used as probiotics are sensitive or have a low level of resistance to antibiotics, so they usually cannot achieve their beneficial effect, since they are killed by the applied antibiotics. This work aimed to develop the highly resistant Lactiplantibacillus plantarum subsp. plantarum ATCC14917 to cephalexin and evaluate its recovery effects of antibiotic-resistant L. plantarum on the antibiotic-disturbed intestinal microbiota using a mice model.

Methods and results

After successive growth in lactic acid bacteria susceptibility medium broth containing a gradually increasing concentration of cephalexin for 70 days, the minimum inhibitory concentration (MIC) of L. plantarum ATCC14917 to cephalexin significantly increased from 16 to 8192 μg ml−1, but stabilized at 4096 μg ml−1. After sequencing and sequence analysis, no mutated genes were detected on mobile elements, showing that horizontal transfer of mutated genes could not occur. Compared to the control group (Con), feeding mice with cephalexin (1 mg ml−1; Cep) led to a decrease in alpha diversity. However, concurrently used cephalexin and L. plantarum (Cep + LpR) increased the alpha diversity in both microbial richness and diversity. The Cep + LpR group showed a lower distance with the Con group than either Cep or Cep + LpS groups, suggesting that resistant L. plantarum treatment was more effective than the original strain for the recovery of intestinal microbiota. Compared to the cephalexin-treated group, concurrent ingestion of cephalexin together with resistant L. plantarum significantly increased the proportion of beneficial bacteria and decreased Firmicutes/Bacteroidetes ratio and abundance of potential pathogens.

Conclusions

The use of antibiotic-resistant L. plantarum ATCC14917 contributed to a much faster and richer recovery of the gut microbiota disturbed by antibiotic treatment compared to the original strain.
Under-the-radar engagement: how and why news users limit their public expression
Authors: Tenenboim Ori
Published: January 2025

Beyond digital news consumption, users may express themselves in relation to the consumed news—for example, through commenting, sharing, or reacting. They may also limit what is termed here news engagement visibility, the extent to which a user’s involvement with news content can be seen by others. Drawing on privacy calculus theory and literature about engagement, avoidance, and relationship management, this study examines—through 50 in-depth interviews in Canada—how and why news users limit their news engagement visibility. It presents three ways for limiting this visibility, including lower expression volume, more private expression space, or more closed-ended expression type. Furthermore, it introduces the four P’s framework—protection, pointlessness, personality, and particularity—to explain the reasons behind limited news engagement visibility. The study advances the understanding of news engagement by suggesting that it involves the management of visibility boundaries and by elucidating barriers to public expression. The implications of these contributions are discussed.
Endoscopic management to different isolated maxillary fungal pathologies: case series of a tertiary hospital
Authors: Alabdulaal Maria , Almuhanna Zahraa , Alfaleh Moath , Saeed Ghadeer Bu , Alsaid Abdullah , Almomen Ali
Published: January 2025

Isolated maxillary fungal pathologies involve a variety of clinical entities. These include invasive and non-invasive variants, where each has a unique pathogenesis, clinical manifestation, and approach for management. The aim of this case series is to investigate the several ways that fungal infections of the maxillary sinus might present, with the approach to diagnose and manage these conditions. Several discrete maxillary fungal diseases were studied, including fungal ball, acute fulminant invasive fungal sinusitis, allergic fungal sinusitis, and chronic invasive fungal sinusitis at a hospital. For every condition, several treatment options, clinical manifestations, and diagnostic strategies were investigated, which are greatly influenced by the degree of invasiveness as well as the patient’s immunological status. Optimizing patient outcomes, especially in more aggressive types of the disease, requires an early and proper diagnosis. Understanding the various symptoms of these fungal infections is critical for a timely management.
A systematic survey of TF function in E. coli suggests RNAP stabilization is a prevalent strategy for both repressors and activators
Authors: Guharajan Sunil , Parisutham Vinuselvi , Brewster Robert C
Published: January 2025

Transcription factors (TFs) are often classified as activators or repressors, yet these context-dependent labels are inadequate to predict quantitative profiles that emerge across different promoters. A mechanistic understanding of how different regulatory sequences shape TF function is challenging due to the lack of systematic genetic control in endogenous genes. To address this, we use a library of Escherichia coli strains with precise control of TF copy number, measuring the quantitative regulatory input–output function of 90 TFs on synthetic promoters that isolate the contributions of TF binding sequence, location, and basal promoter strength to gene expression. We interpret the measured regulation of these TFs using a thermodynamic model of gene expression and uncover stabilization of RNA polymerase as a pervasive regulatory mechanism, common to both activating and repressing TFs. This property suggests ways to tune the dynamic range of gene expression through the interplay of stabilizing TF function and RNA polymerase basal occupancy, a phenomenon we confirm by measuring fold change for stabilizing TFs across synthetic promoter sequences spanning over 100−fold basal expression. Our work deconstructs TF function at a mechanistic level, providing foundational principles on how gene expression is realized across different promoter contexts, with implications for decoding the relationship between sequence and gene expression.
Beyond metaplasia: unraveling the complex pathogenesis of autoimmune atrophic gastritis and its implications for gastric cancer risk
Authors: Zhang Tai , Tang Xudong
Published: January 2025

Autoimmune gastritis (AIG) is a chronic inflammatory condition characterized by immune-mediated destruction of gastric parietal cells, leading to oxyntic atrophy, achlorhydria and hypergastrinemia. While AIG was historically linked to gastric adenocarcinoma and type I neuroendocrine tumors (NETs), recent evidence suggests the risk of adenocarcinoma in AIG is lower than previously believed, particularly in Helicobacter pylori (H. pylori)-negative patients. The increased cancer risk in AIG is mainly attributed to concurrent or past H. pylori infection. The incidence of gastric adenocarcinoma in AIG ranges from 0.12% to 0.5% per year, with cumulative risks over 10 years reported at 1–3%. In contrast, type I NETs are more commonly associated with AIG, with an annual incidence of 0.68–2.8% and cumulative rates as high as 15.3% over 5 years. Adenomatous polyps, which can progress to malignancy, have been reported in 4.6–13.6% of AIG patients. This review examines the immune and molecular mechanisms underlying AIG’s pathogenesis, positioning it as a model of immune-mediated epithelial injury with limited carcinogenic potential. AIG is associated with reparative metaplastic phenotypes, such as pseudopyloric and complete intestinal metaplasia, which contrast with the more aggressive incomplete intestinal metaplasia observed in H. pylori-induced gastritis. The reduced risk of adenocarcinoma in AIG is attributed to the absence of H. pylori, a T cell-dominated microenvironment, minimal macrophage infiltration and protective factors such as altered gastric microbiota, epigenetic modifications, increased CD3+ intraepithelial cytotoxic T lymphocytes and reduced interleukin-33/interleukin-13 signaling. Although AIG is linked to preneoplastic changes, its primary neoplastic risks include the development of type I NETs and adenomatous polyps, which carry a potential for malignant transformation, necessitating long-term surveillance in patients with hypergastrinemia, extensive atrophy and associated gastric lesions. Challenges persist in distinguishing AIG from other atrophic gastritis types due to limitations in serological and histological markers, but emerging diagnostic tools, such as lymphocyte profiling and molecular assays, promise improved accuracy. This review underscores the importance of tailored surveillance and management strategies to address the distinct neoplastic risks associated with AIG, while advocating for further research into its immune landscape and molecular pathways.
Evacuations as Displacement: Conceptual and Legal Challenges
Authors: McAdam Jane
Published: January 2025

This article seeks to conceptualise evacuations as a form of human mobility. Although evacuations represent a large proportion of annual global “displacement” in official figures, they are rarely analysed as such and instead tend to be viewed positively as a form of rescue – saving lives by moving people away from danger. By reorienting the orthodox starting point for evacuations – the “rescue” paradigm – this article hypothesises that while evacuations can be life-saving, they can also displace people and undermine long-term protection needs. From this perspective, evacuees are not simply passive recipients of humanitarian assistance: they are rights-holders with legal entitlements. The first part of the article explores the complexity and contradictions involved in characterising evacuations as a form of displacement, including whether there are qualitative differences between different types of displacement. Building on this, the second part examines key legal issues that arise in evacuations, including when evacuations constitute “arbitrary”, as opposed to “permissible”, displacement. In doing so, it brings into focus issues that may be obscured if evacuations are viewed predominantly as a proactive measure to move people to safety, rather than as a potential indicator of risk and vulnerability.
Altered Effective Connectivity Within a Thalamocortical Corollary Discharge Network in Individuals With Schizophrenia
Authors: Lehet Matthew , Yao Beier , Tso Ivy F , Diwadkar Vaibhav A , Fattal Jessica , Bao Jacqueline , Thakkar Katharine N
Published: January 2025

Background and Hypothesis

Sequential saccade planning requires corollary discharge (CD) signals that provide information about the planned landing location of an eye movement. These CD signals may be altered among individuals with schizophrenia (SZ), providing a potential mechanism to explain passivity and anomalous self-experiences broadly. In healthy controls (HC), a key oculomotor CD network transmits CD signals from the thalamus to the frontal eye fields (FEF) and the intraparietal sulcus (IPS) and also remaps signals from FEF to IPS.

Study Design

Here, we modeled fMRI data using dynamic causal modeling (DCM) to examine patient-control differences in effective connectivity evoked by a double-step (DS) task (30 SZ, 29 HC). The interrogated network was formed from a combination of (1) functionally identified FEF and IPS regions that robustly responded on DS trials and (2) anatomically identified thalamic regions involved in CD transmission. We also examined the relationship between clinical symptoms and effective connectivity parameters associated with task modulation of network pathways.

Study Results

Network connectivity was indeed modulated by the DS task, which involves CD transmission. More importantly, we found reduced effective connectivity from thalamus to IPS in SZ, which was further correlated with passivity symptom severity.

Conclusions

These results reaffirm the importance of IPS and thalamocortical connections in oculomotor CD signaling and provide mechanistic insights into CD alterations and consequently agency disturbances in schizophrenia.
Genome sizes of animal RNA viruses reflect phylogenetic constraints
Authors: Takada Kosuke , Holmes Edward C
Published: January 2025

Animal genomes are characterized by extensive variation in size. RNA viruses similarly exhibit substantial genomic diversity, with genome lengths ranging from 1.7 to ∼64 kb. Despite the myriad of novel viruses discovered by metagenomics, we know little of the factors that shape the evolution of the genome size in RNA viruses. We analyzed the variation in genome sizes across orders and families of animal RNA viruses. We found that RNA viruses can have highly variable genome sizes within and among orders, with the Nidovirales (including the Coronaviridae) exhibiting both significantly larger genomes and a greater range of genome sizes than other orders. In the Bunyavirales, Amarillovirales, Nidovirales, and Picornavirales, the genome sizes of invertebrate-associated RNA viruses were significantly larger than those that infect vertebrates, in contrast to their animal hosts in which vertebrates commonly have larger genomes than invertebrates. However, in the Mononegavirales, vertebrate viruses were significantly larger than those viruses associated with invertebrates. There were similarly complex associations between genome size and patterns of genome segmentation. In the Bunyavirales, Reovirales, and Nidovirales, viruses with segmented genomes, or that possessed a large number of segments, had significantly larger genome sizes than viruses with nonsegmented genomes or a small number of segments, while in Articulavirales, there were no significant differences in genome size among viruses possessing any number of genome segments. More broadly, our analysis revealed that taxonomic position (i.e. RNA virus order) had a greater impact on genome size than whether viruses infected vertebrates or invertebrates or their pattern of genome segmentation. Hence, the phylogenetic constraints on genome size are of sufficient magnitude to shape some other aspects of virus evolution.
Assessment for Enteral Feeding Intolerance by Critical Care Nurses
Authors: Powers Jan , Bourgault Annette M. , Carroll Simmons Jennifer S.
Published: January 2025

Background

Enteral feeding intolerance (EFI) occurs in more than one-third of mechanically ventilated patients, yet the cause of this gastrointestinal dysfunction remains unclear. Assessment and diagnostic criteria are often vague and subjective leading to inaccurate recognition or diagnosis of EFI. Nurses are often unsure or unaware of appropriate assessment methods.

Objectives

The objective of this descriptive study was to determine current practice for assessment of EFI among critical care nurses.

Methods

A national survey to explore EFI assessment practices was conducted with critical care nurses at the American Association of Critical-Care Nurses National Teaching Institute conference in 2022. Nurses completed a 19-item survey to determine assessment practices for EFI among critical care nurses.

Results

A total of 344 nurses completed the survey. The majority of nurses practiced direct care at the bedside for adult critical care patients, held a bachelor’s degree, had 6 to 15 years of nursing experience, and held specialty certification. There was variability among responses to the practice questions in the survey. Seventy-eight percent of the nurses were aware of and had cared for patients with EFI. EFI was assessed by 84% of participants. The most common assessment criterion for EFI was nausea and vomiting. The majority (81%) of respondents measured gastric residual volume routinely or sometimes.

Discussion

This study shows assessment of EFI is not standardized among nurses. This study identifies a need for education about EFI given the lack of understanding of EFI. Findings from this study can be used to inform future research to develop best methods for assessing the presence of EFI.
Recent Advancements in Robotic-assisted Plastic Surgery Procedures: A Systematic Review
Authors: Kawashima Kazuho , Ghali Shadi , Nikkhah Dariush , Esmaeili Ali
Published: January 2025

Background:

There has been a delayed, yet steady uptake of robotic-assisted surgery over the past decade within the field of plastic surgery. In an era of rapidly evolving scientific and technological development, there is a need for an update on the current literature for robotic-assisted plastic surgery procedures.

Methods:

Searches were conducted across major databases, including MEDLINE, Embase, and Central for published literature from March 2023 to December 2024. Only published articles written in English with full texts were considered for the final narrative synthesis.

Results:

Initially, we identified 1200 articles in the database search. Subsequently, 46 articles were included in our final narrative synthesis. Among the selected studies, 4 focused on reconstruction in transoral robotic surgery, 14 on breast surgery, 10 on robotic microsurgery, 5 on abdominal wall reconstruction, 6 on vaginoplasty, and 5 on flap harvest.

Conclusions:

The evidence to support the advantage of robotic plastic surgery procedures over traditional methods is relatively weak. However, there have been some advancements, specifically in transoral robotic surgery, robotic mastectomy, and breast reconstruction. Nevertheless, comprehensive exploration and prospective randomized trials are essential across all procedures to define the role of surgical robots in plastic surgery. The impediments to wider adoption include high costs, disruption to operative flow, and the absence of haptic feedback in robotic-assisted procedures within the specialty.
Meibomian Gland Structure and Function in Patients with Demodex Blepharitis
Authors: Yeu Elizabeth , Koetting Cecelia
Published: January 2025

Purpose:

To compare structural and functional measures of meibomian gland dysfunction (MGD) in eyes with moderate to severe Demodex blepharitis (collarette grade 2-4) compared to those with collarette grade 0 (0-2 collarettes).

Setting:

Private clinical practice.

Design:

Retrospective, single-center, non-interventional, observational study.

Methods:

In this study, case records of patients aged ≥18 years with data available for collarettes and MGD signs (telangiectasia, meibum expressibility, meibum quality, and meibography) were included. Outcome measures were the comparison of the mean telangiectasia score, meibum expressibility score, meibum quality score, and meibomian gland atrophy score between eyes with moderate to severe Demodex blepharitis (collarette grade 2 to 4, or >10 collarettes) and those with collarette grade 0 (0-2 collarettes). Right and left eyes were analyzed separately.

Results:

The mean telangiectasia, meibum quality, and meibomian gland atrophy scores were statistically significantly worse in the collarette grade 2-4 group than in those in the collarette grade 0 group for both right and left eyes (even adjusting for age). There was a positive correlation between collarette grade and telangiectasia, meibum quality and meibomian gland atrophy scores.

Conclusion:

Structural and functional measures of MGD were significantly worse in eyes with collarette grade 2-4 than in those with collarette grade 0. Clinicians should routinely examine their patients for Demodex infestation and signs of MGD and treat both conditions as needed, especially in the perioperative setting.
Torsion and ruptured ovarian cystadenocarcinoma with internal bleeding complicated with retroperitoneal hematoma after tumor transection: A case report
Authors: Tien Chin-Tzu , Cheng Chiu-Hsuan , Hong Mun-Kun
Published: January 2025

Rationale:

Ovarian tumor torsion is a critical gynecological emergency, predominantly affecting women of reproductive age, with benign teratomas being the most common culprits. In contrast, malignant ovarian tumors, such as mucinous cystadenocarcinoma, infrequently present with torsion due to their invasive and angiogenic characteristics. The occurrence of torsion in malignant tumors complicates diagnosis and management, particularly when associated with complications like congestion, infarction, and internal bleeding. This report details a rare case of primary ovarian mucinous cystadenocarcinoma presenting with acute torsion and significant internal bleeding. Our study highlights the diagnostic challenges and the urgent need for clear treatment guidelines, addressing an important gap in the existing literature regarding the management of torsion malignant ovarian tumors. By documenting this case, we aim to contribute to the understanding of this rare condition and provide insights that may help clinicians in similar scenarios.

Patient concerns:

A 51-year-old postmenopausal woman presented with acute abnormal pain. Transvaginal ultrasound examination showed an 8-cm heterogeneous right ovary mass without ovarian blood flow on color Doppler.

Diagnoses:

Laparoscopy revealed torsion and rupture of the right ovarian tumor with 900 mL hemoperitoneum. The patient underwent right salpingo-oophorectomy complicated by continuous oozing and hematoma formation in the infundibular ligament. Unexpectedly, histopathology revealed a mucinous cystadenocarcinoma of the right ovary, pT1c2.

Intervention:

The patient underwent staging surgery and prophylactic hyperthermic intraperitoneal chemotherapy.

Outcome:

After 4 years of follow-up, no tumor recurrence or metastasis was found.

Lessons:

Currently, there are no effective preoperative diagnostic and treatment guidelines for ruptured malignant ovarian tumors with torsion. The possibility of malignancy should be considered, and frozen section biopsy should be considered during surgery. Full detorsion before tumor resection to avoid incomplete pedicle coagulation and bleeding. Specimen removal by in-bag morcellation in minimally invasive surgery to prevent complications related to residual fragments of the specimen or dissemination of an occult malignancy.
Aggressive angiomyxoma of the vagina: A case report and literature review
Authors: Yu Bo Ram , Choi Won Ku , Cho Dong Hyu , Lee Na-Ri
Published: January 2025

Rationale:

Aggressive angiomyxoma (AAM) is an exceptionally rare mesenchymal tumor that predominantly manifests in the female genital organs during the reproductive age. Its rarity alone makes it a fascinating subject for study. The diagnosis of AAM necessitates differentiation from other benign or mesenchymal tumors and can be confirmed through immunohistochemistry (IHC) staining. Surgical resection is the primary treatment, and adjuvant treatment can be used as hormonal therapy with gonadotropin-releasing hormone agonists, selective estrogen receptor modulators, and aromatase inhibitors.

Patient concerns:

A 44-year-old premenopausal Korean woman presented with a growing perineal mass and frequent urination.

Diagnoses:

Histopathological findings confirmed AAM, with IHC staining showing estrogen receptor, progesterone receptor, actin and desmin positivity, and CD34 and S100 negativity.

Interventions:

The mass was excised transvaginally under general anesthesia.

Outcomes:

The patient showed no signs of recurrence 6 months postoperatively.

Lessons:

AAM in the vagina is a rare tumor that requires differential diagnosis using IHC staining. Previously, we reviewed reported cases and confirmed the feasibility and effectiveness of surgery as the main treatment. This might reassure us about the potential successful treatment of AAM. Adjuvant hormonal therapy with gonadotropin-releasing hormone agonists, selective estrogen receptor modulators, and aromatase inhibitors can further reduce the risk of recurrence.
Questionnaire and analysis of the standardized use of home self-monitoring portable blood glucose meters
Authors: Zhang Hongrui , Cheng Lu , Li Meng , Ye Xiongwei , Wan Xiaochen
Published: January 2025

To evaluate the accuracy of home self-monitoring portable blood glucose meters, we analyzed the current problems of patients using portable blood glucose meters and put forward reasonable suggestions. A self-designed questionnaire was used to survey 142 patients and 132 healthcare professionals. The questionnaire consisted of 16 items with an overall score ranging from 1 to 13 (with a higher score indicating better experience). The study included adult patients with diabetes mellitus type 1 or type 2. The patients’ awareness rate for standardized use of portable blood glucose meters at home was at 31.42%. Specifically, awareness of blood collection specifications was at 15.85%, standardized operation at 42.53%, and accuracy of results at 0%. A significant majority (81.69%) scored between 0 and 5 points in home blood glucose meter use, with knowledge and practice scores consistently below 3 points. Notably, no patients conducted a formal comparison of various meters. Despite this, their confidence level in the portable blood glucose meter results was as high as 71.1%. Urgent measures are needed to educate patients on proper usage and encourage regular instrument comparisons.
Evaluation of the effect of carotid sinus blockade on hemodynamic stability in carotid surgery: A retrospective study
Authors: Çetinkaya Dilek , Bozdoğan Ramazan Faruk , Şahin Aykut , Dernek Sadettin
Published: January 2025

This study assesses the effect of carotid sinus blockade applied with a local anesthetic on hemodynamic parameters during carotid endarterectomy (CEA) operations performed under general anesthesia. The medical records of patients who underwent CEA under general anesthesia between January 2020 and December 2022, were retrospectively reviewed. It was recorded whether the patients received carotid sinus block with 2 mL of 2% prilocaine. Intraoperative and 48-hour postoperative hemodynamic data were examined in the patients included in the study. A total of 129 patients were evaluated in the study, with 70 patients who received carotid sinus blockade (Group I) and 59 patients who did not receive blockade (Group II) during CEA. The comparison of heart rate variability immediately before clamping, immediately after clamping, and at 5, 10, and 20 minutes post-clamping indicated a significantly greater reduction in Group II compared to Group I (P < .05). In the postoperative period, the total dose of glyceryl trinitrate administered was 40.8 ± 31.9 mg in Group I and 53 ± 17.2 mg in Group II, showing a statistically significant difference (P = .001). Additionally, blood pressure measurements during this period were significantly higher in Group II than in Group I (P < .05). While the application of a local anesthetic during CEA appears to provide better intraoperative heart rate and postoperative blood pressure control, attributing these results solely to local anesthesia may not be entirely accurate. Hemodynamic instability observed during and after CEA is influenced by various factors.
The case for value-based care in kidney transplantation: insights into geography, growth, and financial models
Authors: Paulus Amber B. , Kumar Dhiren , Pontinha Vasco M.
Published: January 2025

Purpose of review

Kidney transplantation (KT) is the preferred treatment for end-stage renal disease (ESRD), yet systemic challenges, including geographic disparities, impede equitable access. This review evaluates transplant center activity and regional disparities using recent trends and discusses the potential of value-based care (VBC) models like the proposed Increasing Organ Transplant Access (IOTA) model to address these challenges.

Recent findings

Analysis of Organ Procurement and Transplantation Network (OPTN) data from 2021 to 2023 identified 185 of 322 transplant centers as potentially eligible for VBC inclusion. High ESRD prevalence states like Texas, California, and New York have the largest number of centers, while states like Wyoming and Vermont lack operational centers, creating access barriers. Growth in KT rates following the 2014 Kidney Allocation System (KAS) reforms has stabilized at 3–5% since 2023. Geographic disparities persist, with regions like the South Atlantic and Pacific showing high transplant activity but unmet demand relative to ESRD prevalence.

The proposed IOTA model could mitigate disparities by incentivizing infrastructure investment and prioritizing equitable access. Tailored VBC strategies are essential to addressing regional needs and improving KT equity and outcomes nationwide.
A 5-Year Single-center Experience on the Use of Emicizumab Prophylaxis in Children With Severe Hemophilia A With and Without Factor VIII Inhibitors
Authors: Ahmed Hasan Esraa Mohamed , Motwani Jayashree
Published: January 2025

Objective:

Emicizumab promotes efficacious hemostasis in persons with hemophilia A persons with hemophilia A with and without inhibitors. Primary analyses of real-world data and clinical trials have shown emicizumab efficacy and safety; however, long-term data are limited.

Methods:

This retrospective study was conducted to assess real-world long-term outcomes of pediatric patients on emicizumab in our hemophilia center between the period of February 2018 and September 2023. Relevant demographic and clinical data were gathered.

Results:

Seventy-eight patients were enrolled. Previously untreated patients and minimally treated patients accounted for 14.1% and 10.3% of our recruited patients, respectively. One of 5 patients with active inhibitors experienced a single recombinant activated factor VII-treated bleeding episode while on emicizumab prophylaxis. Twenty-eight (28/78) patients underwent surgical/dental procedures without bleeding complications except for 2 patients (7.1%). Thirty-three patients experienced 62 factor-treated bleeding episodes with only 11 imaging-confirmed joint/muscle bleeding episodes among 8 patients. No major safety concerns were reported in the study and emicizumab was discontinued in 5 patients (2 for antidrug antibody development, 2 for joint bleeding, and 1 for non-compliance).

Conclusion:

Emicizumab prophylaxis was well tolerated with no new safety concerns, and 45 patients (57.7%) of our cohort exhibited zero-treated bleeds, which was comparable to other published experiences.
Lessons Learned in Virtual Launch of an Antenatal Opioid Exposure Study During the COVID-19 Pandemic
Authors: Newman Jamie E. , Dhawan Megan , Clarke Leslie , Owen Sharon , Beiersdorfer Traci , Parlberg Lindsay M. , Merhar Stephanie , DeMauro Sara B. , Lorch Scott A. , Wilson-Costello Deanne , Ambalavanan Namasivayam , Peralta-Carcelen Myriam , Poindexter Brenda , Davis Jonathan M. , Mack Nicole , Limperopoulos Catherine , Bann Carla M.
Published: January 2025

Background

The COVID-19 pandemic prompted researchers to develop new ways to design and launch studies and recruit and retain participants. Pregnant women and infants are considered vulnerable populations in research, and families affected by substance use are particularly difficult to recruit and retain. Recruitment for studies involving medical technologies such as MRI can also be difficult due to misconceptions and fear of the technologies.

Objectives

To describe “lessons learned” during the launch of the Outcomes of Babies with Opioid Exposure (OBOE) study, including successes and challenges when working with high-risk infants and families and the importance of engaging participants through recruitment materials and retention efforts.

Methods

The OBOE study is a multisite prospective longitudinal cohort study comparing infants with antenatal opioid exposure to unexposed controls from birth to 2 years of age. Chi-square tests were used to examine refusal reasons among caregivers of eligible infants by exposure group and differences in 6-month retention among subgroups based on social determinants of health.

Results

Four factors were essential in establishing the Consortium, implementing the study, and retaining participants: (a) creating venues for collaboration, (b) pivoting from in-person to virtual training, (c) anticipating potential enrollment barriers and addressing them directly, and (d) engaging participants through recruitment materials and retention efforts. With these factors in place, only 5% of caregivers of eligible opioid-exposed infants and 8% of control infants declined to participate in the study because of MRIs. Of 310 enrolled infants, 234 infants had attended the 6-month visit. Subgroups of enrolled infants were similar in retention at 6 months.

Discussion

Reporting our successes and challenges in setting up a nationwide consortium during the pandemic may help other consortia that need to be set up virtually. We anticipated that the serial MRIs would be a barrier to participation; however, few indicated they refused to participate because of MRIs, suggesting our efforts to address this potential barrier to enrollment were successful.
Effective nursing strategies to identify and prevent sexual violence risk in adolescents
Authors: Biedlingmaier Renee , Heavey Elizabeth
Published: January 2025

This article informs nurses of evidence-based nursing interventions to ensure adolescents receive appropriate sexual violence screening and responses.
Caring for a patient with appendiceal cancer
Authors: Pullen Richard L.
Published: January 2025

Appendiceal cancer (AC) is a rare malignancy, occurring in 1 to 2 individuals per million annually in the US. It is often diagnosed incidentally during appendectomies or imaging for unrelated conditions. This article explores the risk factors, clinical presentation, diagnostic methods, pathology, staging, and treatment options for AC, highlighting disparities in access to care across different demographics. This article also emphasizes the importance of early detection and tailored management strategies to enhance nurses' understanding and improve outcomes for patients with this uncommon but significant disease.
Growing grit
Authors: Keperling Heather
Published: January 2025

Purpose:

Grit, or a person's “perseverance and passion for long-term goals,” is a noted character trait for success. This qualitative descriptive study explored the experiences and challenges faced by nursing students, focusing on how these experiences shaped their educational journeys and exploring the role of perseverance and passion in nursing education and its potential for student success in a nursing education program.

Methods:

Purposive sampling was utilized to select study participants from higher education institutions in Southeastern Pennsylvania. To guide the interview, an interview protocol was developed which included a comparison table of the open-ended interview and probing questions and the Grit-S scale, an 8-item self-evaluation tool that quantifies perseverance of effort (perseverance) and consistency of interest (passion). Data were collected via semistructured virtual interview. Data were managed with ATLAS.ti 9 used in coding and analyzing transcripts and creating data visualization.

Results:

The data analysis identified four themes: managing goals, confronting challenges, emerging interests, and experiencing supportive relationships. The study identified student perceptions of the factors that impacted their perseverance for long-term goals and their passion for nursing, assisting in their success.

Conclusion:

Recognizing the crucial role played by perseverance and passion in a student's success empowers nursing programs and faculty to consider implementing strategies to nurture interest and support students as they pursue their long-term objectives. The results of this study supported the interplay of perseverance and passion. Recommendations for nursing education include fostering supportive relationships and student-centered instructional techniques as well as organizing seminars or similar programs during the first year of their curriculum to grow perseverance and inspire passion.
Intratumoral Heterogeneity of Primary Breast Cancer on 18F-FES PET/CT and dbPET Anticipated a Heterogeneous Response to Chemotherapy
Authors: Kitano Yurika , Miyake Kanae K. , Shimizu Yoichi , Kawashima Masahiro , Nakamoto Yuji
Published: January 2025

A 59-year-old woman with cT3N3M1 invasive breast cancer (ER low positive, PgR positive, HER2 negative) underwent PET/CT and dedicated breast PET scans using 18F-FDG and 18F-fluoroestradiol (18F-FES). While most primary tumor regions displayed low FES uptake, regions of high FES uptake were also identified. Following chemotherapy with the paclitaxel and bevacizumab, 18F-FDG PET/CT demonstrated a favorable response, but residual disease was noted in areas with high FES uptake on the pretreatment images. This case illustrated that 18F-FES PET can depict intratumoral heterogeneity within the primary tumor, which was strongly associated with a heterogeneous response to subsequent chemotherapy.
Significantly Elevated FDG Activity in Esophageal Inflammatory Myofibroblastic Tumor of a Pediatric Patient
Authors: Cheng Xin , Xue Liyan , Lin Lin , Li Jing , Wang Xuejuan
Published: January 2025

A 13-year-old girl presented with dysphagia underwent contrast-enhanced CT and endoscopy. The CT revealed cervical esophageal wall thickening with heterogeneous enhancement. Microscopic examination of the biopsy specimen suggested a possible mesenchymal tumor. She underwent an 18F-FDG PET/CT scan for staging. The scan showed local thickening of the cervical esophageal wall with heterogeneous and significantly elevated FDG activity. Subsequent immunohistochemical staining and fluorescence in situ hybridization confirmed the diagnosis of esophageal inflammatory myofibroblastic tumor.
Solitary Axillary Lymph Node Metastasis From Ovarian Cancer on 18F-FDG PET/CT
Authors: Yang Liu , Dong Ping , Li Lin
Published: January 2025

Solitary axillary lymph node metastasis from ovarian cancer is rare. A 74-year-old woman who had undergone hysterectomy and bilateral salpingo-oophorectomy for ovarian cancer 2 years ago presented to our hospital with enlarged axillary lymph node. 18F-FDG PET/CT revealed left axillary lymphadenopathy with an SUVmax of 8.92. The postbiopsy pathology confirmed metastasis of poorly differentiated ovarian adenocarcinoma. This case highlights the need to consider ovarian cancer metastasis in cases of solitary axillary lymphadenopathy with intense FDG uptake, especially in patients with a recent history of ovarian cancer.
Detection and characterization of Hepatitis B virus double-stranded linear DNA-derived covalently closed circular DNA in chronic hepatitis B patients
Authors: Liu Hsin-Ni , Kim Elena , Wang Zhili , Nguyen ThiThuyTu , Shieh Fwu-Shan , Liu Yuanjie , Ghany Marc G. , Chung Raymond T. , Sterling Richard K. , Lin Selena Y , Guo Haitao , Lau Daryl T-Y , Su Ying-Hsiu
Published: January 2025

Background and Aims

Hepatitis B virus (HBV) generates a double-stranded linear DNA (dslDNA) byproduct during replication. This dslDNA can undergo intermolecular and intramolecular nonhomologous end-joining (NHEJ) recombination, resulting in viral integration and dslDNA derived covalently closed circular DNAs (dsl-cccDNAs), respectively. The insertions and deletions (INDELs) at the end-joining site around the direct repeat (DR) 1 motif have been used to differentiate dsl-cccDNA from the authentic cccDNA. The frequency and characteristics of dsl-cccDNA in chronic hepatitis B (CHB) patients remain unclear.

Methods

HBV-targeted next-generation sequencing (NGS) was used to identify 32 dsl-cccDNA positive candidates, 22 HBeAg(+) and 10 HBeAg(-), from 56 liver biopsies of antiviral treatment-naive CHB patients for dsl-cccDNA confirmation and characterization by cccDNA-PCR NGS. INDELs within the DR2-1 region (nt 1600–1840) of the cccDNA were analyzed.

Results

Various clonally expanded, heterogenous ∼22-nt deletions in the X-gene were detected in all 32 samples, which are likely quasi-species from the authentic cccDNA. We, therefore, defined dsl-cccDNA only by the presence of INDELs clustered at the DR1 surrounding region (nt 1800–1840). The percentage of dsl-cccDNA in total cccDNA was higher among HBeAg(+) compared to HBeAg(-) samples [11.32 (3.24–26.94)%vs.7.72 (2.16–28.23)%, p=0.01]. The diversity of dsl-cccDNA species correlated with cccDNA levels (log-transformed; r=0.82, p<0.001), HBeAg(+) CHB (p<0.001), and serum HBV DNA (p<0.001).

Conclusions

dsl-cccDNA is more prevalent and heterogenous among the HBeAg(+) CHB subjects, which is likely due to the active viral cccDNA transcription and reverse transcription at the HBeAg(+) phase. The existence of replication-defective dsl-cccDNA may facilitate immune evasion and HBV integration, and complicate HBV pathogenesis. The potential impact of dsl-cccDNA in HBV therapeutic response deserves further assessment.
Who am I? Optimal Tissue for Germline Genetic Testing Post-Stem Cell Transplantation
Authors: Mertens Matthias , Sadlo Mona , Kühl Jörn-Sven , Metzeler Klaus , Zschenderlein Louisa , Edelmann Jeanett , Lehmann Claudia , Thull Sarah , Karakaya Mert , Velmans Clara , Tumewu Theresa , Böhme Matthias , Klötzer Christina , Weigert Anne , Vucinic Vladan , Hentschel Julia , Mertens Mareike
Published: January 2025

With advancements in genetic diagnostics and genotype-based therapeutics, the demand for germline genetic testing in post-hematopoietic stem cell transplantation patients is increasing. Due to genetic chimerism, blood samples can no longer be used for germline testing after transplantation. This study aims to identify the most suitable tissue for germline analysis following stem cell transplantation by investigating alternative tissue sources. Buccal swab, eyebrow hair, and nail samples were analyzed for donor-derived DNA using next-generation sequencing and short tandem repeat analysis, with linear regression used for evaluation. Factors such as HLA match, transplantation type, sex, and time after transplantation were also evaluated for their effect on donor-derived DNA share. Buccal swab and nail samples exhibited 25% and 22% higher proportions of donor-derived DNA compared to eyebrow hair follicles, respectively. The median donor DNA share in eyebrow hair follicles was 1% for NGS and 3% for STR. Factors such as matched related donors, higher HLA match, different donor-recipient sex, and longer time post-transplantation correlated with lower donor DNA shares. Eyebrow hair follicles are a promising tissue for accurate germline genetic testing in post-SCT patients. Patient characteristics like donor relatedness, HLA match, sex match, and time after transplantation should be considered.
A Deep Learning Pipeline for Morphological and Viability Assessment of 3D Cancer Cell Spheroids
Authors: Mali Ajay K. , Murugappan Sivasubramanian , Prasad Jayashree Rajesh , Tofail Syed A. M. , Thorat Nanasaheb D.
Published: January 2025

Three-dimensional (3D) spheroid models have advanced cancer research by better mimicking the tumour microenvironment compared to traditional 2D dimensional (2D) cell cultures. However, challenges persist in high-throughput analysis of morphological characteristics and cell viability, as traditional methods like manual fluorescence analysis are labour-intensive and inconsistent. Existing AI-based approaches often address segmentation or classification in isolation, lacking an integrated workflow.

We propose a scalable, two-stage deep learning pipeline to address these gaps: (1) a U-Net model for precise detection and segmentation of 3D spheroids from microscopic images, achieving 95% prediction accuracy, and (2) a CNN Regression Hybrid method for estimating live/dead cell percentages and classifying spheroids, with anR2value of 98%. This end-to-end pipeline automates cell viability quantification and generates key morphological parameters for spheroid growth kinetics.

By integrating segmentation and analysis, our method addresses environmental variability and morphological characterization challenges, offering a robust tool for drug discovery, toxicity screening, and clinical research. This approach significantly improves efficiency and scalability of 3D spheroid evaluations, paving the way for advancements in cancer therapeutics.
Wing Hinge Dynamics Influence Stroke Amplitudes in Flapping Wing Insects: A Frequency Response Approach
Authors: Casey Cailin , Cote Braden , Heveran Chelsea , Jankauski Mark
Published: January 2025

Flapping insects are thought to leverage resonance or vibration amplification to reduce the energetic costs of flight. However, precisely where resonance occurs within their flight systems remains unclear. We hypothesized that most insects flap near a resonance where elastic deformation occurs primarily within the wing hinge rather than the flexible thorax. To test this, we measured the linear frequency response relating thorax deformation to wing stroke angle in sacrificed honeybees and army cutworm moths. Using experimental data, we developed a linear model of the flight system, which we then extended to incorporate nonlinear effects associated with large wing stroke angles. Our findings revealed that both species flap below the linear resonance of the wing hinge. At large wing stroke angles, nonlinear aerodynamic damping reduces the resonant frequency, causing both species to flap above resonance. However, the wing-hinge resonant frequency varied significantly depending on whether angular position, velocity or acceleration was considered as the frequency response output. Based on these observations, we hypothesized that cutworm moths flap between angular position and velocity resonances, whereas honeybees flap at the angular velocity resonance. The collective results suggest that insects flap in proximity to a wing hinge resonance rather than a thorax resonance.
Aging directs the differential evolution of KRAS-driven lung adenocarcinoma
Authors: Lazure Felicia , Drapela Stanislav , Liu Xiaoxian , Lockhart John H. , Kashfi Hossein , Sarigul Nadir , Ilter Didem , Flores Elsa R. , Wang Xuefeng , Smalley Inna , Jaeger Alex , Yu Xiaoqing , Gomes Ana P.
Published: January 2025

Lung adenocarcinoma (LUAD), the most common histological subtype of lung cancer(1, 2), is a disease of the elderly, with an average age of diagnosis of about 70 years of age(3). Older age is associated with an increased incidence of KRAS-driven LUAD(4), a particularly deadly type of LUAD characterized by treatment resistance and relapse. Despite this, our understanding of how old age shapes KRAS-driven LUAD evolution remains incomplete. While the age-related increase in cancer risk was previously ascribed to the accumulation of mutations over time, we are now beginning to consider the role of host biology as an independent factor influencing cancer. Here, we use single-cell RNA-Sequencing of KP (KrasG12D/+; Trp53flox/flox) LUAD transplanted into young and old mice to define how old age affects LUAD evolution and map the changes that old age imposes onto LUAD’s microenvironment. Our data demonstrates that the aged lung environment steers LUAD evolution towards a primitive stem-like state that is associated with poor prognosis. We ascribe this differential evolution, at least in part, to a population of rare and highly secretory damage-associated alveolar differentiation intermediate (ADI) cells that accumulate in the aged tumor microenvironment (TME) and that dominate the niche signaling received by LUAD cells. Overall, our data puts aging center stage in coordinating LUAD evolution, highlighting the need to model LUAD in its most common context and creating a framework to tailor future cancer therapeutic strategies to the age of the patient to improve outcomes in the largest and most vulnerable LUAD patient population, the elderly.