bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy, Safety and Retention in Care Among Adolescents and Youth With HIV on Long-Acting Injectable Cabotegravir/Rilpivirine Treatment: Real-World Observational Cohort Outcomes
Authors: Williams Tierra , Unternaher Justin , Koay Wei Li Adeline , Anderson Lorato , Bright Kimberly , Mareuil Joanna , Rakhmanina Natella
Published: January 2025

Background:

Long-acting injectable (LAI) cabotegravir/rilpivirine (CAB/RPV) can improve adherence among adolescents and youth with HIV (AYHIV). We evaluated LAI CAB/RPV treatment outcomes among AYHIV.

Methods:

An observational cohort study of AYHIV <25 years initiated LAI CAB/RPV from October 2021 to June 2024 as a standard of care. Descriptive data included demographics (age, race/ethnicity and gender/sexual orientation), body mass index, HIV history, efficacy (CD4, HIV RNA and resistance), safety and retention in care.

Results:

Twenty-five AYHIV (48% cisgender females; median age, 19 years; 64% with perinatally acquired HIV; median body mass index = 25.3 kg/m2; 52% virally suppressed for ≥6 months) received LAI CAB/RPV for a median duration of 11.8 (range, 0.8–31.3) months. Majority (n=24; 96%) initiated monthly LAI CAB/RPV injections, and 19 AYHIV (76%) switched to bimonthly injections. Seven AYHIV (28%) experienced transient viremia episodes (1–5/person; ranges, 48–1100 copies/mL) with most (78%) occurring within the initial 12 months, all episodes resolved at retesting after 3 to 91 days and none resulted in CAB and/or RPV resistance. Injection-associated pain/discomfort was mild to moderate and decreased over time. Grade 2 adverse events were self-resolved and included 3 AYHIV with postinjection adverse reactions and 1 AYHIV with QTc prolongation. Three cisgender female AYHIV became pregnant and continued LAI CAB/RPV. There were no discontinuations, missed or delayed injections. All AYHIV were virally suppressed at the end of the study follow-up.

Conclusions:

We report 100% engagement in care and viral suppression among 25 AYHIV on LAI CAB/RPV during study follow-up. More data are needed to evaluate the long-term outcomes and sustainability of LAI CAB/RPV treatment in AYHIV.
The efficiency of venturi versus peristaltic based phacoemulsification in femtosecond laser cataract surgery
Authors: Scott Rachel A , Holtmeyer Caleb J , Parker Travis M , Willis Jessica K , Scott Wendell J , Olson Randall J
Published: January 2025

Purpose:

To compare the efficiency of peristaltic vs venturi vacuum platforms when applied to the femtosecond treated cataract.

Setting:

Outpatient Eye Center, Mercy Health System, Springfield, MO, USA.

Design:

This is a prospective randomized controlled trial of 111 patients with moderate nuclear sclerosis scheduled for bilateral routine laser cataract surgery (clinicaltrials.gov; NCT03970525).

Methods:

Patients were randomized to receive surgery in one eye with a peristaltic system and the other with a venturi system. The vacuum and phaco power were the same for both systems. The primary outcomes were EFX, UST (ultrasound time), PIOT (phaco in/out time), surgery time (speculum in/out time), and the ECC (endothelial cell count).

Results:

The type of vacuum/phacoemulsification system used during laser cataract surgery had a significant impact on the four procedural outcomes. Specifically, phacoemulsification energy (EFX), ultrasound time (UST), phaco tip in/out time (PIOT), and total microscope time (speculum in/out case time) were lower when the venturi system was used compared to the peristaltic system (t(100)=-4.28, p <.001). The vacuum system used did not impact the uncorrected visual acuity (UCVA), best corrected visual acuity (BCVA) or central cornea thickness (CCT). ECC decreased 6.38% with venturi and 8.32% with peristaltic (t(87) = 1.19, p = .235). There were no complications.

Conclusion:

Venturi-based phaco was more efficient than peristaltic, based on energy and time, when used for removal of the femtosecond treated cataract.
Machine Learning-based Prediction of Mortality Among Malnourished Patients Hospitalized With Inflammatory Bowel Disease
Authors: Limketkai Berkeley N. , Li Zhaoping , Mullin Gerard E. , Parian Alyssa M.
Published: January 2025

Background:

Malnourished patients hospitalized with inflammatory bowel disease (IBD) have a high risk of morbidity and mortality. Risk stratification can help identify patients who are most in need of medical and nutritional intervention.

Goal:

This study aimed to develop a machine-learning model that accurately predicts mortality in hospitalized IBD patients with protein-calorie malnutrition (PCM).

Study:

Hospitalized adults with IBD and PCM were identified in the 2016 to 2019 National Inpatient Sample (NIS). Random Forest Classifier (RFC) and Extreme Gradient Boosting (XGB) models were constructed using a 70% randomly sampled training set from the years 2016 to 2018, tested using the remaining 30% of 2016 to 2018 data, and externally validated using 2019 data. Patient characteristics were evaluated using weighted estimates that accounted for the complex sampling design of the NIS.

Results:

Among 879,730 malnourished patients hospitalized for IBD, 1930 (0.2%) died. Compared with malnourished patients who survived, those who died were generally older, White, had ulcerative colitis with multiple comorbidities, and admitted on the weekend. The accuracy, precision, sensitivity, and specificity for both models were 0.99, 0.98, 0.99, and 0.99, respectively. The area under the receiver operating characteristic curve was 0.91 for both models.

Conclusion:

Machine learning models can accurately predict mortality in malnourished patients hospitalized with IBD, while solely relying on readily available clinical data. Further integration of these tools into clinical practice could improve risk stratification of IBD patients with PCM and potentially reduce mortality in this high-risk population by prompting earlier intervention.
A case report of gastric antral vascular ectasia treated by endoscopic band ligation combined with lauromacrogol injection
Authors: Chen Linbo , Sun Keke , Chen Yukai , Hu Pingping , Lin Qi
Published: January 2025

Rationale:

Gastric antral vascular ectasia (GAVE) is a rare acquired lesion characterized by vascular dilation in the gastric antrum, frequently results in occult or overt gastrointestinal bleeding. Endoscopic intervention remains the cornerstone of therapy. Argon plasma coagulation was previously considered a first treatment option. But recently, endoscopic band ligation (EBL) has emerged as an alternative, increasingly favored for its safety and efficacy. Nonetheless, a consensus on the most effective treatment approach has yet to be established.

Patient concerns:

A 74-year-old female was hospitalized for persistent chest tightness and dyspnea for 1 year. Physical examination showed an anemic appearance with normal blood pressure. Upon admission to the hospital, the blood routine examination revealed severe anemia and the fecal occult blood test was persistently positive.

Diagnoses:

The endoscopic observations and histological evidence led to a diagnosis of GAVE for the patient.

Interventions:

Considering the poor response to prior pharmacotherapy, endoscopic intervention was selected for this hospitalization. The initial EBL alone did not yield particularly satisfactory results. Combining EBL with lauromacrogol injection as a subsequent treatment resulted in encouraging outcomes.

Outcomes:

At the 6-week follow-up, the patient exhibited a negative fecal occult blood test, normalization of hemoglobin level, and endoscopic images demonstrated near complete resolution of vascular ectasias.

Lessons:

The combination of EBL with lauromacrogol injection has shown a satisfactory short-term outcome, providing a new option for the endoscopic management of GAVE. However, its long-term efficacy still requires further observation.
Differential diagnosis of thrombosis and myxoma in unusual heart positions by dual-energy CT multiple parameter imaging: A case series
Authors: Wang Yunting , Cui Yuxin , Chen Yunbing , Lan Honglin
Published: January 2025

Rationale:

Thrombus is the most common occupying lesion in the cardiac chambers, it is often distinguished from cardiac neoplastic occupations. Among them, the most common is cardiac myxoma, whose imaging manifestations are often confused with thrombus. However, the 2 types of lesions have different therapeutic strategies and are both potentially high-risk sources of embolism, so early differentiation between intracardiac thrombus and cardiac tumor is essential. In this study, we intend to investigate the value of dual-energy computed tomography (CT) in the differential diagnosis of cardiac thrombus and myxoma by retrospectively analyzing the dual-energy CT-related parameters of 2 cases of intracardiac thrombus and 1 case of cardiac myxoma.

Patient concerns:

Three cases of masses located in uncommon areas of the heart with comparable imaging characteristics are presented in this study.

Diagnoses:

Echocardiography revealed an isoechoic mass in the cardiac chambers, while CT scans showed a hypodense occupancy with varying morphologies. Postoperative pathology or follow-up after treatment confirmed 1 case as a right ventricular thrombus, another as a right atrial thrombus, and the third as a right ventricular myxoma.

Interventions:

In this study, we conducted a retrospective analysis of dual-energy CT-related parameters in 2 cases of intracardiac thrombus and 1 case of cardiac myxoma.

Outcomes:

Our findings indicate notable differences in the slopes of the energy spectral curves, mean iodine density, and effective atomic number between the intracardiac thrombus and myxoma cases.

Lessons:

Drawing upon existing literature, we propose combining different quantitative analysis methodologies to create a more objective foundation for distinguishing between cardiac thrombosis and myxoma.
The role of inflammatory factors in mediating the causal effects of type 1 diabetes mellitus on idiopathic pulmonary fibrosis: A two-step Mendelian randomization study
Authors: Fan Qinglu , Meng Yang , Nie Zhihao , Yi Zuohuizi , Chen Liao , Xie Songping
Published: January 2025

While recent studies suggested a potential causal link between type 1 diabetes mellitus (T1DM) but not type 2 diabetes mellitus (T2DM) and idiopathic pulmonary fibrosis (IPF), the involved mechanism remains unclear. Here, using a Mendelian randomization (MR) approach, we verified the causal relationship between the two types of diabetes mellitus and IPF and investigated the possible role of inflammation in the association between diabetes mellitus and IPF. Based on genome-wide association study (GWAS) summary data of T1DM, T2DM, and IPF, the univariable MR, multivariable MR (MVMR), and mediation MR were successively used to analyze the causal relationship. Inverse variance weighted was used as the main method to infer the causal effect, together with a series of sensitivity analyses. The univariable MR showed that only T1DM increased the risk of IPF, and there was no significant causal relationship between T2DM and IPF. The MVMR further verified that there was an independent direct causal effect of T1DM on IPF. Further mediation analysis showed that this effect was partly mediated by increasing C-X-C motif chemokine ligand 10 (CXCL10) and interleukin-12 subunit beta (IL-12B). In conclusion, T1DM is related to an increased risk of IPF. Notably, the causal effect was partially mediated by CXCL10 and IL-12B. Hence, monitoring T1DM patients may help in the early detection and prevention of IPF.
A case report of anaphylactic shock caused by lidocaine
Authors: Mi Jiang-Hui , Shen Ting-Ting , Wang Hong-Wei
Published: January 2025

Rationale:

Local anesthesia is a widely used technique for emergency wound closure, with lidocaine among the most commonly employed local anesthetics. Allergic reactions to lidocaine are rare, with anaphylaxis being even more uncommon.

Patient concerns and diagnosis:

This report describes a 72-year-old male patient who presented with a right foot injury and underwent wound suturing under lidocaine local anesthesia. Although the procedure went smoothly, the patient developed dizziness, cold sweats, hypotension, and bradycardia 30 minutes later, leading to a diagnosis of anaphylaxis due to lidocaine allergy.

Interventions and outcomes:

Immediate treatment for anaphylactic shock was initiated, including intramuscular administration of adrenaline, fluid resuscitation, anti-inflammatory agents, antihistamines, oxygen therapy, and symptomatic supportive care. Within 20 minutes of active treatment, the patient’s symptoms were effectively controlled. The patient was safely discharged after 24 hours of observation. Health education was provided to enhance self-management skills.

Lessons:

Although rare, anaphylaxis induced by lidocaine can be fatal. Early recognition, prompt intervention, thorough preoperative assessment, and careful postoperative monitoring are critical to improving survival rates.
Circulating inflammatory cytokines and colorectal cancer: New insights from Mendelian randomization
Authors: Fan Qinglu , Wang Jing , Tian Miao , Sawut Abdulla , Xiao Di , Yi Zuohuizi , Chen Liao
Published: January 2025

Colorectal cancer (CRC) is one of the most common cancers worldwide and inflammation is believed to play an important role in CRC. In this study, we comprehensively analyzed the causal association between 91 circulating inflammatory cytokines and the risk of CRC using Mendelian randomization (MR). Based on genome-wide association study summary statistics, we examined the causal effects of 91 circulating inflammatory cytokines on CRC. A series of MR methods, including bidirectional MR, replication sample MR, and multivariable MR, were employed to provide more robust causal estimates. After the validation with 3 MR methods and a series of sensitivity analyses, 2 circulating inflammatory factors were found to be significantly associated with the risk of CRC at the genetic level. Specifically, genetically predicted circulating levels of glial cell line-derived neurotrophic factor (GDNF) (OR = 1.12; 95% CI: 1.05–1.19; P = 2.72 × 10-4) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) (OR = 0.93; 95% CI: 0.91–0.99; P = 1.00 × 10-2) exerted causal effects on CRC risk. In conclusion, this study suggests that increased circulating levels of GDNF and TRAIL are associated with a higher and lower risk of CRC, respectively. GDNF and TRAIL may be 2 potential therapeutic targets that deserve future investigation.
Rare dual MYH9–ROS1 fusion variants in a patient with lung adenocarcinoma: A case report
Authors: Luo Tian , Ji Wentao , Guo Weihong , Zhang Dandan , Liang Jianping , Lv Yanhua
Published: January 2025

Rationale:

ROS proto-oncogene 1 (ROS1) fusion is a rare but important driver mutation in non-small cell lung cancer, which usually shows significant sensitivity to small molecule tyrosine kinase inhibitors. With the widespread application of next-generation sequencing (NGS), more fusions and co-mutations of ROS1 have been discovered. Non-muscle myosin heavy chain 9 (MYH9) is a rare fusion partner of ROS1 gene as reported. Here, we report an even rare case with coexistence of short and long variants MYH9–ROS1 fusions at the RNA level accompanied by TP53 mutation, insensitively to antitumor therapy.

Patient concerns and diagnosis:

A 37-year-old nonsmoking man was diagnosed with stage IVB (T4N3M1c) lung adenocarcinoma. The tumor was identified to have MYH9 (exon 37)–ROS1 (exon 35) rearrangement with TP53 mutation at the DNA level by DNA-NGS analysis of lymph node biopsy tissue in March 2023. Interestingly, it was transcribed into coexistence of short and long variants MYH9–ROS1 (M36, R36) and MYH9–ROS1 (M36, R35) fusions at RNA level by RNA-NGS analysis.

Interventions:

First-line tyrosine kinase inhibitors crizotinib was given firstly, showing partial response (PR) but significant progression within 3 months. To determine the resistance mechanism to crizotinib and the genetic variation, DNA-NGS and RNA-NGS were performed again on a new biopsy tissue of lymph node in August 2023.

Outcomes:

Rare coexistence of short and long variants of MYH9–ROS1 fusions was identified again, but the typical mechanisms of crizotinib resistance were not observed. Switching to lorlatinib resulted in brief PR about 2 months. Subsequent 2 courses of system chemotherapy provided short-term PR less than 2 months. The patient died with a total survival of 10 months.

Lessons:

We must pay attention to rare dual short and long variants of the MYH9–ROS1 fusions, it may affect the efficacy of ROS1-tyrosine kinase inhibitors targeted therapy.
Effectiveness of regorafenib in second-line therapy for advanced hepatocellular carcinoma: A systematic review and meta-analysis
Authors: Shen Yunzhi , Bai Yu
Published: January 2025

Background:

In patients with advanced hepatocellular carcinoma (HCC) following sorafenib failure, regorafenib has been used as an initial second-line drug. It is unclear the real efficacy and safety of sorafenib-regorafenib sequential therapy compared to placebo or other treatment (cabozantinib or nivolumab or placebo) in advanced HCC.

Methods:

Four electronic databases (PubMed, Embase, Web of Science, and Ovid) were systematically searched for eligible articles from their inception to July, 2024. Included articles were selected based on strict eligibility criteria. Review Manager 5.4 software were performed for statistical analysis.

Results:

Ten studies with 2349 HCC patients of whom 1370 received regorafenib treatment, and 979 underwent cabozantinb, nivolumab or placebo were selected for meta-analysis. The results of our systematic review and meta-analysis found regorafenib could significantly prolong overall survival (standardized mean difference [SMD] = 0.16, 95% CI = 0.02 to 0.29, P = .02) than other treatment (cabozantinib or nivolumab or placebo) in second-line treatment of HCC following sorafenib failure. No significant difference in progression-free survival (SMD = −0.03; 95% CI = −0.13 to 0.06; P = .53), overall response rate (risk ratio [RR] = 0.59; 95% CI = 0.24 to 1.47; P = .26), disease control rate (RR = 1.23; 95% CI = 0.7 to 2.16; P = .48) between 2 groups. Subgroup analysis demonstrated that nivolumab has better overall response rate results than regorafenib (RR = 0.38; 95% CI = 0.24 to 0.61; P < .0001).

Conclusions:

Compared with other treatment (cabozantinib or nivolumab or placebo), regorafenib seemed to be more effective for patients with HCC who have not responded to initial sorafenib treatment.
Effects of abdominal, vaginal, and laparoscopic hysterectomies on total oxidant/antioxidant levels: A prospective observational study
Authors: Tayarer Aybuke , Tas Emre Erdem , Senat Almila
Published: January 2025

This prospective observational study aimed to compare abdominal hysterectomy (AH), vaginal hysterectomy (VH), and total laparoscopic hysterectomy (TLH) in terms of oxidative stress (OS) by measuring serum levels of total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI). Of the 3 groups, namely, AH, VH, and TLH, 22 patients were enrolled in each to investigate the aim of the study mentioned above. Patient demographics, clinical and surgical characteristics, and preoperative and postoperative (0th and 24th hours) serum TAS, TOS, and OSI levels were investigated. The groups differed significantly based on surgical indications (P < .001). While abnormal uterine bleeding was more prevalent in the AH (95.5%) and TLH (77.3%) groups, pelvic organ prolapse (POP) was more prevalent in the VH group (90.1%). The mean age and menopausal patient rates were significantly higher in the VH group than in the AH and TLH groups (P < .001). The groups did not differ significantly in terms of simultaneous bilateral salpingo-oophorectomy rates (P = .10). However, additional POP surgery was performed in 14 patients in the VH group. The mean operative time was significantly shorter in the AH group than in the VH and TLH groups (P = .001). The groups did not differ significantly based on either the preoperative or postoperative serum TAS levels (P > .05). Furthermore, the change in serum TAS levels over time was not significant in any of the groups (P > .05). In contrast, preoperative serum TOS and OSI levels were significantly higher in the VH group than in the AH and TLH groups (P < .05). The groups did not differ significantly in terms of serum TOS and OSI levels at 0th and 24th hours postoperatively (P > .05). Serum TOS and OSI levels increased dramatically over time in the AH and TLH groups (P < .05), but not in the VH group (P > .05). post hoc analysis showed that the changes in serum TOS and OSI values in the AH and TLH groups were between the preoperative and postoperative 0th hour levels (P < .001). Our results indicated that the total antioxidant capacity was preserved in all 3 techniques. However, VH causes less OS than the other hysterectomy techniques.
Comparison of the efficacy between Super-Path and Watson-Jones approaches in the management of early femoral head necrosis
Authors: Xu Yong , Zeng Ping
Published: January 2025

This study compares and investigates the efficacy of 2 different surgical methods for early stage femoral head necrosis and analyze the factors affecting surgical outcomes and long-term femoral head survival. A retrospective analysis was conducted on the clinical data of 48 patients (52 hips) with femoral head necrosis who underwent either the Super-Path or Watson-Jones approach from January 1, 2016, to January 1, 2024. Harris scores at multiple time points before and after surgery were compared using repeated-measures analysis of variance (ANOVA), and a COX proportional hazards model was used to analyze risk factors. The baseline data of the 2 groups were comparable (P > .05). There was no significant difference in preoperative Harris scores or scores at 3 and 12 months postoperatively (t = 0, P = 1; t = 0.719, 0.476; P = .716, .477). However, a significant difference was found at 36 months postoperatively (t = 2.118, P = .04). The preoperative stage of femoral head necrosis, patient gender, and surgical method were significant risk factors. The survival curves showed similar survival rates for the first 10 months, with no significant difference at 36 months (P = .5139). Both surgical approaches were effective in improving short-term hip function but did not show sustained long-term improvement. The Super-Path approach demonstrated better long-term outcomes compared to the Watson-Jones approach, influenced by surgical and temporal factors and preoperative staging. The COX model indicated that preoperative staging, female gender, and the surgical procedure were positively correlated with the risk of femoral head necrosis.
Second Primary Neoplasms in Pediatric Cancer Survivors With Single Institution Experience From Turkey
Authors: Hekimci Özdemir Hamiyet , TürkYilmaz Sena , Ataseven Eda , Özek Gülcihan , Aksoylar Serap , Arun Kamer Serra , Kantar Mehmet
Published: January 2025

Background:

This study aims to establish the characteristics of second primary neoplasms (SPNs) and the long-term follow-up status of a tertiary pediatric oncology center.

Methods:

Records of 1799 patients followed up in the pediatric oncology division between January 1981 and December 2022 were evaluated retrospectively.

Results:

Thirty-four (1.9%) cases of secondary neoplasms were identified throughout 42 years. The 5-year and 10-year cumulative incidence was 1% and 4%, respectively. The 3 most common SPNs were thyroid carcinomas (TC), central nervous system (CNS) tumors, and leukemias. The shortest median latent period of SPN detection was 15.5 (2 to 35) months in secondary leukemias, whereas 8 (0 to 17) years in all SPNs. Secondary solid tumors that occurred within the radiation field were TC and meningiomas with a 5.5 (3 to 12) and 16 (6 to 22) years latency period, respectively. Ten patients died; the median death time from the diagnosis of SPN was 10 months in all secondary leukemias and 3.5 months in CNS tumors. The 5-year overall survival was 91%, with a median follow-up time of 13.1 years in all patients with SPN.

Conclusions:

Considering the SPN-inducing effects of radiotherapy and chemotherapy, patient-protective improvements in treatment protocols are required. Multidisciplinary and long-term follow-up is essential even in adulthood because of the long latency period of some SPN occurring in pediatric cancer survivors.
A Rare Case of Peritoneal Mesothelioma Detected by 18F-AlF-NOTA-Octreotide PET/CT
Authors: Hou Guozhu , Cheng Xin , Jiang Yuanyuan , Zheng Rong , Wang Xuejuan
Published: January 2025

We present a case of 37-year-old man with multiple masses in the abdominal and pelvic cavity who underwent 18F-AlF-NOTA-octreotide PET/CT. The masses demonstrated heterogeneously increased uptake on 18F-AlF-NOTA-octreotide PET/CT and were suggestive of neuroendocrine tumor. However, the histopathological examinations confirmed the masses to be peritoneal mesothelioma. This case indicated that peritoneal mesothelioma should be kept in mind as one of the differential diagnoses for 18F-AlF-NOTA-octreotide-avid tumors.
A Very Atypical Meckel Diverticulum on 99mTcO4− Scintigraphy
Authors: Foran Ann , Attaseth Pensiree , Grant Frederick D. , Zhuang Hongming
Published: January 2025

Typical Meckel diverticulum on 99mTcO4− scintigraphy usually appears early in the dynamic imaging in the right lower quadrant of the abdomen, without change of location during the study. We report a case of pathology-proven Meckel diverticulum a 7-year-old boy, which appeared only on the later part of the 99mTcO4− study in the midline upper pelvis which gradually changed location during the study.
Icariside II attenuates isoproterenol-induced myocardial ischemia by regulating NLRP3/Caspase-1 axis
Authors: Feng Wenzhong , Fang Dongfei , Tang Fangying , Gao Jianmei , Chen Fuchao , Li Zhihao , Duan Cancan , Zhang Yan , Yu Ming , Wang Pingping , Zhang Jianyong
Published: January 2025

Background

Epimedii Folium, first recorded in the Shennong’s Classic of Materia Medica (Shen Nong Ben Cao Jing), is a traditional Chinese medicine (TCM) known for its effects of “benefiting Qi and strengthening the heart.” Icariside II (ICS II) is one of the main active components of Epimedii Folium, possessing cardiovascular protective and anti-inflammatory properties. However, the potential mechanisms of ICS II on myocardial ischemia (MI) remain unclear.

Objective

The aim of the study was to investigate the effects and preliminary molecular mechanisms of ICS II in treating isoproterenol-induced MI in rats.

Methods

A rat model of MI was established by subcutaneous injection of isoproterenol. Electrocardiography, echocardiography, myocardial enzymes analysis, heart weight index, triphenyltetrazolium chloride staining, histopathology, TUNEL staining, RT-qPCR, and Western blot were employed to evaluate the effects and preliminary molecular mechanisms of ICS II on MI rats.

Results

Pharmacodynamic studies suggested that ICS II inhibited ST-segment elevation in electrocardiograms, improved cardiac function, reduced heart weight index and myocardial enzyme levels, decreased myocardial infarct size, alleviated cardiac histological damage, and inhibited apoptosis, thereby exerting cardioprotective effects in MI rats. Further studies revealed that ICS II may partially inhibit the expression of NLRP3/Caspase-1 axis-related targets at both protein and mRNA levels.

Conclusions

O`nary molecular mechanisms may be related to inhibiting the activation of the NLRP3/Caspase-1 axis to alleviate inflammatory responses.
Trauma-Informed Self-Care Practices in Speech-Language Pathology and Related Professions
Authors: Evans Kelli
Published: January 2025

Practitioners in speech-language pathology and related fields work with clients who have experienced trauma, which can lead to secondary traumatic stress (STS), vicarious traumatization (VT), and compassion fatigue in the practitioner. Trauma-informed self-care (TISC) strategies may be one way to mitigate negative stress-related outcomes. This scoping review aims to determine what is known about TISC practices for (1) speech language pathologists and (2) related professions (e.g., education, mental health professions, healthcare). Online databases were searched to identify peer-reviewed publications that measured or described TISC practices at the individual or organizational level for professionals or trainees/training programs for SLP and related professions. Findings were screened using a two-level process resulting in 1 relevant article in the SLP literature and 26 in related professions. Meaning units related to TISC practices were extracted from each article and analyzed to develop themes. In related professions, both individual TISC strategies (e.g., stress management practice, self-care plans) and organizational strategies in training programs and the workplace (e.g., integrating self-care into professional-level policies and practice standards, creating a culture of care, and providing TIC training) are recommended to support practitioner wellbeing. Knowledge about TISC strategies for the specific discipline of speech-language pathology is limited; however, literature in related professions can offer guidance to develop individual and organizational guidelines for SLPs.
Optimizing Electroconvulsive Therapy With E-Field Modeling
Authors: Ren Caili , Kung Simon , Croarkin Paul E. , Opitz Alexander , Forester Brent P. , Hermida Adriana P. , Mueller Martina , Pagali Sandeep R. , Petrides Georgios , Seiner Stephen J. , Yoon Isabel A. , Lapid Maria I.
Published: January 2025

Electroconvulsive therapy (ECT) is an effective treatment for severe depression, especially in treatment-resistant cases. However, its potential cognitive side effects necessitate careful dosing to balance therapeutic benefits and cognitive stability. Recent advances in electric field (E-field) modeling offer promising avenues to optimize ECT dosing. This review synthesizes current knowledge on E-field modeling in ECT and explores its clinical applications. It examines the variability in E-field strengths and distributions induced by ECT and their impact on clinical outcomes. Additionally, the relationship between E-field strengths, neuroplasticity, and therapeutic efficacy is discussed. Translational studies of E-field-informed ECT are highlighted, emphasizing individualized optimal amplitude dosing and potential clinical applications. This review provides useful insights into how E-field modeling can improve the effectiveness of ECT while minimizing adverse effects, helping guide future research and clinical practice.
A Bayesian framework for ranking genes based on their statistical evidence for differential expression
Authors: Hoerbst Franziska , Sidhu Gurpinder Singh , Omori Thelonious , Tomkins Melissa , Morris Richard J.
Published: January 2025

Advances in sequencing technologies have revolutionised our ability to capture the complete RNA profile in tissue samples, allowing for comparative analyses of RNA levels between developmental processes, environmental responses, or treatments. However, quantifying changes in gene expression remains challenging, given inherent biological variability and technological limitations. To address this, we introduce a Bayesian framework for differential gene expression (DGE) analysis. Our framework unifies and streamlines a complex analysis, typically involving parameter estimations and multiple statistical tests, into a concise mathematical equation. This allows statistical evidence for differential expression to be computed rapidly and transparently. We show how this approach can be used to evaluate variabilty of individual genes between replicates. A comparison of our framework with existing tools revealed differences that can be explained by commonly employed thresh-olds in other packages. This motivated us to explore ranking genes based on their statistical evidence as opposed to a binary classification as DEGs. Our analysis leads us to advocate the use of Bayes factors within a rank-based approach. This framework offers enhanced computational efficiency and delivers a transparent way to analyse, interpret and communicate DGE results.
Epigenetic dysregulation of metabolic programs mediates liposarcoma cell plasticity
Authors: Pimenta Erica M. , Garza Amanda E. , Camp Sabrina Y. , Park Jihye , Hoffman Samantha E. , Valderrábano Laura , Fu Jingxin , Bi Kevin , Karam Julie , Titchen Breanna M. , Khandekar Melin J. , Shannon Erin , Kang Yun Jee , Nag Anwesha , Thorner Aaron R. , Raut Chandrajit P. , Hornick Jason L. , Merriam Priscilla , Solimini Nicole L. , George Suzanne , Demetri George D. , Van Allen Eliezer M.
Published: January 2025

Sarcomas are rare connective tissue cancers thought to arise from aberrant mesenchymal stem cell (MSC) differentiation. Liposarcoma (LPS) holds valuable insights into dysfunctional differentiation given its well- and dedifferentiated histologic subtypes (WDLPS, DDLPS). Despite well-established differences in histology and clinical behavior, the molecular pathways underlying each subtype are poorly understood. Here, we performed single-nucleus multiome sequencing and spatial profiling on carefully curated human LPS samples and found defects in adipocyte-specific differentiation within LPS. Loss of insulin-like growth factor 1 (IGF1) and gain of cellular programs related to early mesenchymal development and glucagon-like peptide-1 (GLP-1)-induced insulin secretion are primary features of DDLPS. IGF1 loss was associated with worse overall survival in LPS patients. Throughin vitrostimulation of the IGF1 pathway, we identified that DDLPS cells are deficient in the adipose-specific PPARG isoform 2 (PPARG2). Defects in IGF1/PPARG2 signaling in DDLPS led to a block in differentiation that could not be fully overcome with the addition of exogenous IGF1 or the pro-adipogenic agonists to PPARG and GLP-1. However, we noted upregulation of the IGF1 receptor (IGF1R) in the setting of IGF1 deficiency, which promoted sensitivity to an IGF1R-targeted antibody-drug conjugate that may serve as a novel therapeutic strategy in LPS. In summary, lineage-specific defects in adipogenesis drive dedifferentiation in LPS and may translate into selective therapeutic targeting in this disease.
Comparative spatial transcriptomics of hair follicle-T cell interactions in mouse, dog and human reveals conserved drivers of primary cicatricial alopecia
Authors: Yıldız-Altay Ümmügülsüm , Adhanom Rutha , Abdi Warda , Romasco Andrew , You Lauren , Santacruz Elise , Shakiba Saeed , Daga Mridushi , Tang Qi , Olivera Matthew , Cicuto Thomas , Bretheau Floriane , Baer Christina , Arjomandnejad Motahareh , Keeler Allison , Bui Helen , Shokrani Babak , Almela Ramon , Byrd Angel S. , Frey Cheri , Richmond Jillian M.
Published: January 2025

Primary cicatricial alopecias (PCA) encompass several autoimmune disorders characterized by scarring hair loss. Many of these conditions are lymphocytic and are thought to be driven by T cell populations. Here, we sought to characterize potential T cell-hair follicle communication pathways in the microanatomical niche using spatial transcriptomics across 3 mammalian species including a novel mouse model, spontaneous disease in companion dogs and human archival diagnostic biopsies. Flow cytometry of mouse model skin confirmed loss of CD34+ bulge cells and keratinocytes, and bulk microarray and histology revealed expression of collagens and development of fibrosis.In vivoear imaging in mice engrafted with Kikume photoconvertible OT1 CD8+ T cells confirmed long-lived RFP+ T cells in skin arrest near hair follicles and recruit other GFP+ T cells. OT1 T cells expressed CD69, CD103, CD122 and CD62L, which is a binding partner of CD34. Digital spatial profiling using CD3, CD8 and CD45 cell masking identified CXCR3 ligands and IFN response genes in hair follicles, and “metabolic” pathways in T cells, which were also recapitulated in dog and human biopsies. Bulk human RNA as well as spatial analysis of perifollicular T cells confirmed enrichment ofCD69andSELL/CD62L. Different pathways predominated in other CD3+ regions of interest in CD4+ driven conditions including mucocutaneous lupus erythematosus and subacute cutaneous lupus erythematosus. Last, we identify novel drug-targetable pathways, namelyCFDandS100A8/9, that could be further explored to disrupt processes in these conditions through veterinary and human trials.
WASTER: Practicalde novophylogenomics from low-coverage short reads
Authors: Zhang Chao , Nielsen Rasmus
Published: January 2025

The advent of affordable whole-genome sequencing has spurred numerous large-scale projects aimed at inferring the tree of life, yet achieving a complete species-level phylogeny remains a distant goal due to significant costs and computational demands. Traditional species tree inference methods, though effective, are hampered by the need for high-coverage sequencing, high-quality genomic alignments, and extensive computational resources. To address these challenges, this study introduces WASTER, a novelde novotool for inferring species trees directly from short-read sequences. WASTER employs a k-mer based approach for identifying variable sites, circumventing the need for genome assembly and alignment. Using simulations, we demonstrate that WASTER achieves accuracy comparable to that of traditional alignment-based methods, even for low sequencing depth, and has substantially higher accuracy than other alignment-free methods. We validate WASTER’s efficacy on real data, where it accurately reconstructs phylogenies of eukaryotic species with as low depth as 1.5X. WASTER provides a fast and efficient solution for phylogeny estimation in cases where genome assembly and/or alignment may bias analyses or is challenging, for example due to low sequencing depth. It also provides a method for generating guide trees for tree-based alignment algorithms. WASTER’s ability to accurately estimate trees from low-coverage sequencing data without relying on assembly and alignment will lead to substantially reduced sequencing and computational costs in phylogenomic projects.
Cell-cultured PDMS vascular model to allow placement of implant devices
Authors: Okuno Taku , Ito Kazuyo , Funamoto Kenichi , Yoshino Daisuke
Published: January 2025

Background

A stent maintains normal blood flow by expanding a stenotic artery from the inside. Stents currently in clinical use are mechanically sub-optimized and, therefore, exert excessive mechanical stimuli on the vascular wall. This can lead to arterial inflammation and potentially in-stent restenosis. To optimize the force exerted by a stent on the vascular wall, we should understand, reproduce, and analyze in detail the mechanical field to which the stented vessel is exposed. However, to date, noin vitromodel has been established that can adequately evaluate the mechanical effects of a stent on the vascular wall and be constructed without relying on a laboratory’s know-how. This study aims to develop a three-dimensionalin vitrovascular model that allows stent placement and to provide the details of its construction method.

Methods

Polydimethylsiloxane (PDMS) was used to mimic the adventitial structure of arteries. Human carotid artery endothelial cells (HCtAECs) were then seeded on the luminal surface and cultured for 24 h to form a confluent monolayer (intima). The constructed model was installed in the flow-exposure culturing system, and hemodynamic stimulation (two types of shear stress (SS); 0.5 Pa and 2.3 Pa) was applied to the HCtAECs inside to reproduce the physiological state of blood vessels. In addition, a self-expanding stent was placed in the model during perfusion culture.

Results

We examined the performance of the developed model based on quantitative evaluations of endothelial morphology in response to SS and in-stent endothelialization. Exposure to SS for 24 and 48 h caused endothelial orientation and elongation in the direction of flow, confirming the physiological responses of blood vessels. We were also able to quantitatively evaluate endothelial migration (endothelialization) to the stent.

Discussion

Our model can reproduce the mechanical field inside the stented blood vessel, including hemodynamic stimuli. Based on the results obtained, the developed cell-cultured vascular model has sufficient performance to be used not only for quantitative evaluation of in-stent endothelialization but also for optimization of the mechanical fields in the stented vessel.
Cell type-specific eQTL detection from single-cell RNA-seq reveals post-transcriptional regulatory mechanisms in human islets
Authors: de Winter Twan J.J. , Sovrovic Miha , Dekker Esmée , de Graaf Natascha , Sun Han , Johnson James D. , MacDonald Patrick E. , Gloyn Anna L. , Carlotti Françoise , de Koning Eelco J.P. , Alemany Anna
Published: January 2025

Gene regulatory networks (GRN) must be robust to maintain cellular identity across individuals yet flexible to accommodate population genetic variants. Therefore, comparing expression quantitative trait loci (eQTL) in health and disease can reveal hidden players in GRN and post-transcriptional regulation. Here, we developed a computational pipeline to investigate the gain and loss of eQTLs in the 3’ untranslated region of genes using single-cell RNA sequencing. We repurposed datasets from human islets of donors with and without type 2 diabetes (T2D), and found that beta cells lose identity by gaining alpha cell-specific eQTLs in T2D. By integrating the eQTL landscape with islet miRNA expression, we inferred miRNA-mediated gene regulation in islets. Further validation of miR-127-5p targetingPTENmRNA revealed its association with EGFR signaling and insulin secretion. Hence, our pipeline provides a flexible framework to unravel post-transcriptional regulatory mechanisms in health and disease with cell type resolution.
Single-cell differential detergent fractionation for detection of cytokeratin 8 proteoforms
Authors: Khartchenko Anna Fomitcheva , Lam Trinh , Herr Amy E.
Published: January 2025

Simultaneous profiling of proteoforms and nucleic acids at the single-cell level, i.e., multi omics, directly links the central dogma. However, current single-cell approaches are limited in their ability to identify proteoforms while preserving the nucleus for further analysis. This limitation is especially pronounced in proteins where their proteoforms present diverse biological functions such as cytokeratin 8 (CK8), which, while commonly known for its structural role, is also involved in several diseases. Here, we present a single-cell western blot (scWB) integrated with differential detergent fractionation (DDF) to selectively solubilize and separate CK8 proteoforms while preserving nuclear integrity for subsequent nucleus-based assays. We report on assay development, including screening a panel of lysis buffers based on nonionic detergents and electrophoresis conditions to achieve a separation resolution between two proteoforms of up to 0.94 with an electric field of 30 V/cm, while preserving an intact nucleus. The cytoplasm-specific lysis approach (DDF buffer) demonstrated comparable solubilization efficiency to whole-cell solubilization (RIPA buffer), achieving proteoform solubilization in 14.3% and 10.3% of solubilized cells using DDF and RIPA buffers, respectively, while keeping the nucleus intact. To understand the broad applicability of the assay conditions, we scrutinized electrophoresis performance for resolving CK8 proteoforms across a panel of widely used breast cancer cell lines (MCF7, SKBR3, and MDA-MB-231), showing presence of proteoforms only in MCF7. Our approach allows for tailored solubilization, achieving reliable proteoform detection and nuclear retention across different cell types. Proteoform profiling at the single-cell level forms a basis for the exploration of the role of specific CK8 molecular forms in cellular processes.
LEVERAGING TRANSFER LEARNING FOR HIGH-ACCURACY PHENOTYPIC SCREENING IN ZEBRAFISH IMAGE ANALYSIS
Authors: Jayaraman Varshini Uma , Medishetti Raghavender , Ghosh Shreetama , Chatti Kiranam , Uppada Mahesh Kumar , Oruganti Srinivas
Published: January 2025

This paper presents a method for classifying zebrafish images captured before and after drug administration. Leveraging the power of transfer learning and fine-tuning, the approach effectively overcomes the challenges of limited datasets in biomedical imaging. By employing a pre-trained convolutional neural network (CNN) as the base model, transfer learning allows us to utilize learned features from large-scale image datasets, significantly reducing training time and computational resources. Fine-tuning specific layers of the model on our zebrafish dataset further enhances its ability to detect subtle visual differences induced by drug administration. The proposed approach achieves high accuracy in classifying zebrafish images, demonstrating its potential as a reliable tool for analysing phenotypic changes due to pharmacological interventions. This model could be instrumental in accelerating drug discovery and research in zebrafish-based assays, offering a scalable and efficient solution for image-based biomedical analysis.
Genomic reconstruction ofBacillus anthracisfrom complex environmental samples enables high throughput identification and lineage assignment in Pakistan
Authors: Podowski Justin C , Forrester Sara , Yaqub Tahir , Aqel Amin , Abu-Lubad Mohammad , Mukhtar Nadia , Aziz Muhammad Waqar , Sardar Nageen , Bin Aslam Hassaan , Pervaiz Hamda , Wolfe Alan J , Schabacker Daniel S
Published: January 2025

Bacillus anthracis, the causative agent of anthrax, is a highly virulent zoonotic pathogen primarily affecting domesticated and wild herbivores. Human exposure toB. anthracisis primarily through contact with infected animals or contaminated animal products. In Pakistan, where livestock vaccines are largely unavailable and infected carcasses are often disposed of improperly, the risk to humans, wildlife and livestock is significant. Currently, diagnosis of anthrax infections and outbreak tracing necessitates the isolation and culturing ofB. anthracis, a process that requires BSL-3 facilities. In this study, we show that positive identification, genome reconstruction and lineage assignment can be accomplished using bioinformatic analysis of DNA extracted directly from environmental samples that would otherwise provide the starting material for isolation and culturing. This approach does not require laboratory target enrichment as is necessary for other pathogens, due in part to the extremely high bacterial load in the bloodstream in the deceased animals. Using these methods, we greatly expand the knowledge of endemicB. anthracisin Pakistan. We provide the first referenceB. anthracisgenomes from Pakistan since the 1970s and identify A.Br.014 Aust94 as a minor circulating sublineage alongside dominant A.Br.047 Vollum. Future work will focus on limits of detection and will determine if this bioinformatic method can be expanded more broadly forB. anthracisor other pathogens to replace typical culture-based methods.