bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell components of tumor microenvironment in lung adenocarcinoma: Promising targets for small-molecule compounds
Authors: Han Mingyu , Wan Feng , Xiao Bin , Du Junrong , Peng Cheng , Peng Fu 
Published: November 2024

Abstract
Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%, mainly including lung adenocarcinoma (LUAD). Tumor microenvironment (TME) has become a new research focus in the treatment of lung cancer. The TME is heterogeneous in composition and consists of cellular components, growth factors, proteases, and extracellular matrix. The various cellular components exert a different role in apoptosis, metastasis, or proliferation of lung cancer cells through different pathways, thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods. This review summarizes the research progress on different cellular components with cell–cell interactions in the TME of LUAD, along with their corresponding drug candidates, suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
High Dose of Liraglutide Impairs Renal Function in Female Hypertensive Rats
Authors: Tonon Firmino Felipe , Peixoto Pollyana , Batista Thatiany Jardim , Escouto Leonardo da Silva , Brasil Girlandia Alexandre , Couto Mariana dos Reis , de Melo Júnior Antonio Ferreira , Bissoli Nazaré Souza 
Published: November 2024

Abstract:
Glucagon-like peptide-1 receptor agonists exhibit beneficial cardiovascular effects. However, the renal effects of different doses of liraglutide in an essential hypertension model have not yet been investigated. Female spontaneously hypertensive rats were treated for 30 days, twice a day, with saline (control) or liraglutide at low (0.06 mg/kg) and high (LH, 0.6 mg/kg) doses. Volume intake and excretion were monitored for a period of 24 hours. In renal tissue, nitrite, nitrate, advanced protein oxidation products, collagen deposition, creatinine (Cr), urea (U), sodium, and potassium were analyzed. Liraglutide reduced body weight gain in both groups. However, in the high dose, it increased urinary volume excretion and sodium/potassium ratio. Both doses reduced the urinary U/Cr ratio and LH increased the serum U/Cr ratio. Advanced protein oxidation products were reduced only in low liraglutide. LH augmented collagen and early markers of kidney injury (blood urea nitrogen, blood urea nitrogen/Cr). LH increased nitrate, reduced nitrite, and caused an aberrant increase in glomerular filtration rate. Both doses' effects were independent of blood pressure and glycemic control. Liraglutide appears to have distinct effects on the hypertensive female kidney depending on the dose, with higher doses impairing kidney function.
Modified pro re nata regimen of brolucizumab in treatment-naive neovascular age-related macular degeneration.
Authors: Lippera Myrta , Feo Alessandro , Del Turco Claudia , Santoru Francesco , Fossati Giovanni , Zollet Piero , Panico Edoardo , Romano Mario R , Querques Giuseppe , Panico Claudio , La Spina Carlo 
Published: November 2024

Purpose-
To study the efficacy and safety of pro re nata regimen of brolucizumab, without loading dose, in treatment-naive patients with neovascular age-related macular degeneration (nAMD).

Case series-
Retrospective, observational study. We included all consecutive patients diagnosed with treatment- naïve nAMD undergoing Brolucizumab in Humanitas eye clinic, Turin, Italy between April 2022 and May 2023. Treatment was performed following pro re nata regimen without loading phase. Injection intervals (time between two injections), adverse events, changes in best corrected visual acuity (BCVA), central macular thickness (CMT), maximal retinal thickness (MRT), intraretinal and subretinal fluid (IRF, SRF) were evaluated descriptively up to one year after the first injection. Twenty-one eyes of 21 patients were included in the study. The mean number of injections was 2.4±0.7 at 3 month, 3.0±2.0 at 6 month, 3.1±2.4 at 9 month and 3.8±2.8 at 12 month, respectively. BCVA significantly improved from 20/80 Snellen (0.6±0.3 LogMar) to 20/50 Snellen (0.4±0.3 LogMar) at month 12 (p = 0.044). CMT and MRT significantly reduced from 426 μm and 606 μm at baseline, to 248 μm and 356 μm at one-year follow-up (p=0.00067 and p=0.02, respectively). SRF and IRF also progressively resolved. On the other hand, intraocular inflammation (IOI) events occurred in 9.5% of cases during follow-up. IOI resolved in all cases with prompt treatment without visual sequelae.

Conclusions-
In our study, pro re nata regimen of brolucizumab without loading phase appears to be an effective treatment option in treatment-naive nAMD patients, with IOI rate similar to the one reported in trials and lower number of injections.
Mechanisms of the Native American pain inequity: predicting chronic pain onset prospectively at 5 years in the Oklahoma Study of Native American Pain Risk
Authors: Rhudy Jamie L. , Kell Parker A. , Brown Taylor V. , Ventresca Hayden M. , Vore Claudia N. , Trevino Kayla , Jones Brandon W. , Lowe Travis S. , Shadlow Joanna O. 
Published: November 2024

Abstract
A pain inequity exists for Native Americans (NAs), but the mechanisms are poorly understood. The Oklahoma Study of Native American Pain Risk (OK-SNAP) addressed this issue and recruited healthy, pain-free NAs and non-Hispanic Whites (NHWs) to attend 2 laboratory visits and assessed mechanisms consistent with the biopsychosocial model of pain: demographics, physical variables, psychosocial factors, and nociceptive/pain phenotypes. Then participants were surveyed every 6 months to assess for chronic pain onset. Results at the 2-year follow-up found that NAs were ∼3x more likely than NHWs to develop chronic pain. Moreover, psychosocial factors (discrimination, stress, pain-related anxiety), cardiometabolic load (higher body mass index and blood pressure, lower heart rate variability), and impaired inhibition of spinal nociception partly mediated the pain inequity. The present study examined mechanisms of chronic pain at the 5-year follow-up for OK-SNAP. Results found that the NA pain inequity worsened—NAs were 4x more likely to develop chronic pain (OR = 4.025; CI = 1.966, 8.239), even after controlling for baseline age, sex assigned at birth, income, and education. Moreover, serial mediation models replicated paths from the 2-year follow-up that linked psychosocial variables, cardiometabolic load, and impaired inhibition of spinal nociception to chronic pain onset. Further, 2 new significant paths were observed. One linked discrimination, stress, sleep problems, and facilitated pain perception to increased pain risk. The other linked discrimination with higher spinal nociceptive threshold and pain risk. These results provide further evidence for a NA pain inequity and identify multiple psychosocial, cardiometabolic, and pronociceptive targets for primary interventions.
The Effect of Interventions on Quality of Life, Depression, and the Burden of Care of Stroke Patients and Their Caregivers: A Systematic Review
Authors: Bakhtiari-Dovvombaygi Hossein , Zare-Kaseb Akbar , Nazari Amir Mohamad , Rezazadeh Yusof , Bahramnezhad Fatemeh 
Published: November 2024

ABSTRACT

BACKGROUND: The impact of stroke is a global concern for health policymakers. A large proportion of survivors require long-term support from family members who are typically unprepared for their caregiving duties. This study determined the effect of different interventions on quality of life (QoL), depression, and the burden of care of stroke patients and their caregivers. METHODS: A systematic review was conducted from 2000 up to May 2023. Study inclusion criteria were as follows: individuals serving as informal caregivers for stroke survivors 18 years and older, devoting a significant portion of their time to the care of such survivors; involvement in psychoeducational, informational, supportive, psychosocial, or combined interventions; exposure to standard or conventional care practices; evaluation of outcomes relating to the QoL for stroke caregivers, depression, caregiver burden, and levels of stroke survivors; and consideration of randomized controlled trials and quasi-experimental studies. RESULTS: Thirty-seven studies met the inclusion criteria and were synthesized in this systematic review. Details of intervention were divided into 3 groups: educational and psychoeducational programs, multidisciplinary approaches, and support and caregiver skill-building programs; 12 studies focused on different interventions affecting the QoL, 23 studies focused on the burden of stroke caregivers, and 20 studies focused on depression of stroke patients and their caregivers. CONCLUSION: The desired effectiveness of particular interventions was evident in the results, although conflicting findings have emerged. The study emphasizes the need for well-structured preliminary studies for each intervention type. More studies on interventions and outcomes might lead secondary researchers to conduct analyses to ensure the certainty of results.
Temporal Bone Gunshot Wounds: A Multi-institutional Retrospective Study
Authors: Demirjian Natalie L. , Grande David , Imbery Terence E. , Muelleman Thomas , Walsh Erika M. , Wick Cameron C. , Dewyer Nicholas A. 
Published: November 2024

Objective
To investigate management practices and outcomes in a retrospective cohort of patients who have sustained temporal bone gunshot wounds (TBGSW).

Study Design
Retrospective chart review.

Setting
Five participating hospitals.

Patients
Twenty-two patients met inclusion criteria: experienced a TBGSW, survived ≥30 days following the injury, and were evaluated and managed by a neurotologist between 2019 and 2023.

Interventions
No specific interventions were performed for the purposes of this study.

Main Outcome Measure(s)
Characteristics, evaluation, management, and outcomes of TBGSW survivors.

Results
Patients were found to have a mean age of 33 ± 18 years and were predominantly male (18/22, 81.8%). Majority of patients (17/22, 77.3%) had mastoid injury. Most patients (14/22, 63.6%) had some evidence for vascular injury, most frequently the internal carotid artery (9/22, 40.9%). Almost three-quarters (17/22, 77.3%) of patients had clinical exam findings of facial nerve injury, which was the most common indication for surgery. Otologic surgery was performed in 72.7% (16/22), with delayed adverse events most commonly including cholesteatoma and external auditory canal stenosis. Though evidence for hearing impairment was clinically present in at least 15 of 22 patients (68.2%), hearing rehabilitation was pursued in only two patients.

Conclusion
With increasing numbers of TBGSW survivors, there is a growing need for practicing neurotologists to be familiar with the wide spectrum of injury patterns and possible complications to inform clinical management in these patients. Early neurotologic assessment and follow-up beyond the acute period is crucial to minimize morbidity in this high-risk cohort.
A Novel Delivery Approach of Clinical Inner Ear Gene Therapy
Authors: Zhang Long Long , Wang JingHan , Gao Zi Wen , Lv Jun , Jiang Luo Ying , Cui Chong , Wang Zi Jing , Wang Da Qi , Chen Yu Xin , Fan Xin Tai , Ye Cheng , Wang Hui , Chen Bing , Wang Wu Qing , Li Hua Wei , Shu Yi Lai 
Published: November 2024

Background
To create and develop a delivery approach for clinical inner ear gene therapy, we conducted a study of trans-round window membrane (RWM) microinjection using a pipetting microneedle via transcanal endoscopic ear surgery (TEES).

Methods
The implementation of the trans-RWM microinjection surgery involved seven cadaveric specimens, and the surgical procedures and the pipetting microneedle were developed and optimized. The TEES procedures included tympanic cavity visualization, RWM exposure, stapes footplate perforation, and trans-RWM microinjection. The feasibility of different pipetting microneedles was evaluated during microinjection.

Results
Exposure of the RWM microinjection site could be easily achieved in TEES, and the soft-connected pipetting microneedle was most suitable for the trans-RWM microinjection. The fluid outflow from stapes perforation could be visibly observed during the microinjection, which indicated inner ear drug delivery was successful. This inner ear drug delivery approach was successfully applied in the clinical trial.

Conclusion
The trans-RWM microinjection via the soft-connected pipetting microneedle in TEES was proved to be a feasible delivery approach of the inner ear gene therapy.
Western Blot Characterization of Human Serum Prestin, an Outer Hair Cell Biomarker
Authors: McClure Heather M. , Mirza Mohsin , Adamczyk Patrick , Skoe Erika , Parham Kourosh 
Published: November 2024

Hypothesis
Western blot analysis of human prestin in the blood reveals multiple bands, rather than a single band.

Background
Previously, using the ELISA method, prestin was shown to be a good biomarker of outer hair cell (OHC) health and sensorineural hearing loss that could be measured in the blood. Recently, we found that a Western blot approach in an experimental model demonstrated three prestin bands providing greater insights into prestin in the blood and its origins. This approach has not yet been explored in humans.

Methods
Serum samples from 25 healthy human subjects were analyzed. An automated Western blot for each sample was generated, and bands were analyzed and compared with transient evoked otoacoustic emission levels (TEOAE).

Results
There were five bands at ~32, ~50, ~94, ~139, and ~171 kDa, respectively. Notably, the ~50-kDa band consistently was the most prominent. When the subjects were divided based on TEOAE level, those with high emission levels had a significantly larger ~94-kDa band than those with low emission levels.

Conclusions
Western blot characterization of OHC biomarker prestin in humans shows that the band closest to the previously estimated molecular weight of prestin (81 kDa) is related to a functional measure of OHCs. This finding increases confidence in the value of serum prestin as a biomarker. The Western blot method appears to offer higher-resolution information on serum prestin. Future work will be carried out under pathological conditions to inform on the application of this quantitative method in clinical settings.
A novel γ-chain mutation p.Asp318His in a Chinese family with dysfibrinogenemia
Authors: Zhang Haiyue , Shen Weifeng 
Published: November 2024

Background
Congenital dysfibrinogenemia is characterized by reduced fibrinogen activity, but normal immunoreactive fibrinogen levels. Here, we present a novel case with an elevated risk of thrombosis.

Methods
Coagulation assays, gene analysis, in silico tools, sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), fibrin polymerization, thrombin generation assay, and electron microscopy scanning were utilized to elucidate the pathogenic mechanism.

Results
The proband manifested with a normal immunologic fibrinogen (2.13 g/l) but reduced functional fibrinogen (0.39 g/l). Subsequent genetic analysis unveiled a novel heterozygous mutation, c.1030G>C (p.Asp318His), in the γ-chain D domain of fibrinogen, which was highly conserved in homologous species and led to enhanced thrombin generation capability. The ability of the proband's fibrinogen to polymerize was significantly impaired, with decreased final turbidity. Scanning electron microscopy indicated that the fibers of the proband were thinner than normal, with smaller pores. Thromboelastography (TEG) results demonstrated prolonged K time, decreased angle value, and a normal confidence interval value in the proband.

Conclusion
We present a novel case displaying the γAsp318His mutation, which resulted in dysfibrinogenemia.
Challenges in managing severe homozygous protein c deficiency: a case report
Authors: Almatter Eman , Alsharidah Sondus , Bourhama Mona , Bourusly Maha , Obaid Mohamad Adel 
Published: November 2024

Protein C deficiency is a rare autosomal recessive disorder associated with a high risk of thromboembolic complications. This case report describes the challenges in managing a 23-year-old woman with severe homozygous protein C type 1 deficiency diagnosed since early infancy.
Her medical history included misdiagnosed cellulitis, recurrent thrombosis, and permanent vision loss in one eye. The laboratory workup confirmed a diagnosis of severe protein C deficiency. Management involved a combination of fresh frozen plasma (FFP), protein C concentrate, warfarin, and heparin, with ongoing challenges due to recurrent thrombosis and anaphylaxis to FFP.
This case highlights the challenges in the diagnosis and management of severe protein C deficiency. Although current treatment options provide partial control, further research is crucial to develop safer and more effective therapies to improve long-term outcomes for affected patients.
Intestinal ultrasound accurately predicts future therapy failure in Crohn’s disease patients in a biologics-induced remission
Authors: Albshesh Ahmad , Abend Alon , Yehuda Reuma Margalit , Mahajna Hussein , Ungar Bella , Ben-Horin Shomron , Kopylov Uri , Carter Dan 
Published: November 2024

Background
Intestinal ultrasound (IUS) is used to assess disease activity, complications, and treatment follow-up in Crohn’s disease (CD). Less is known about the association of disease activity on IUS with the risk of future disease relapse during biologically sustained clinical remission in CD.

Aim
The study aimed to investigate the association between IUS activity parameters and subsequent therapy failure in asymptomatic biologically treated patients with CD.

Methods
A retrospective cohort study examined the association between IUS parameters and forthcoming therapy failure (drug discontinuation, dose escalation, corticosteroid use, hospitalization, or surgery) in CD patients on biological therapy in remission.

Results
A total of 57 patients with ileal (65%) or ileocolonic (35%) CD on biological therapy were included in the study. Therapy failure occurred in 50.8% [defined as need for dose escalation (31%), drug discontinuation (51.7%), steroid use (10.5%), and hospitalization (6.8%)] during a median follow-up of 5 (SD + 9.5) months after IUS. On univariate analysis, a bowel wall thickness (BWT) of 2.5 vs. 4 mm (P = 0.005), the existence of an enlarged lymph node (P = 0.02), and the loss of bowel wall stratification (P = 0.01) were correlated with therapy failure. On multivariable analysis, only BWT ≥ 4 mm was associated with the risk of future treatment failure (hazard ratio, 3.7; 95% confidence interval, 0.6–15; P = 0.02).

Conclusion
Our findings suggest that BWT ≥4 mm during clinical remission is associated with subsequent treatment failure in patients with CD treated with biologics. Our results support the use of IUS for monitoring CD during remission and may point to a novel threshold for predicting disease reactivation.
“What Matters” in the Emergency Department
Authors: Chera Tonya , Tinetti Mary , Travers Jasmine , Galske James , Venkatesh Arjun K. , Southerland Lauren , Dresden Scott M. , McQuown Colleen , Gettel Cameron J. 
Published: November 2024

Objective:
To describe “What Matters” to older adults seeking emergency department (ED) care and to identify patient characteristics associated with meeting desired outcomes.

Background:
As part of the 4Ms framework, identifying “What Matters” has been captured across healthcare settings, yet limited attention has been directed to older adults in the ED.

Methods:
We performed a secondary analysis of a multicenter prospective observational study. The study enrolled 1013 patients aged 65 and older during an ED encounter and performed 90-day follow-up interviews. The primary outcome was the quantification of “What Matters” (concerns and desired outcomes) to older adults during emergency care. As secondary outcomes, we assessed concerns at day 90, if desired outcomes were met at follow-up, and patient characteristics associated with outcome achievement by estimating multivariable logistic regression models.

Results:
Older adults reported specific concerns at the time of the ED visit including: (1) symptom identification and/or persistence (31.4%), (2) ability to take care of oneself (19.4%), and (3) end-of-life (17.8%). Desired outcomes expressed by participants included: (1) getting well and symptom resolution (72.0%), (2) obtaining a diagnosis (25.7%), and (3) functional independence (19.5%). At day 90 follow-up, concerns remained similar to the initial ED visit, and the majority of participants (66.2%) achieved their desired outcome. Frailty (adjusted odds ratio = 0.56, 95% CI: 0.38–0.83, P < 0.01) was associated with older adults not meeting their desired outcomes.

Conclusions:
Older adults identified a variety of concerns during emergency care, and two-thirds reported that desired outcomes were met at longitudinal day 90 follow-up.
Genetic determinants of pancreatitis risk in hypertriglyceridemia
Authors: Paquette Martine , Guay Simon-Pierre , Baass Alexis 
Published: November 2024

Purpose of review
In recent years, studies have shed light on the concept of risk heterogeneity among patients with severe hypertriglyceridemia (HTG). Several clinical risk factors for acute pancreatitis have been identified in this population, but the importance of different genetic factors above and beyond triglyceride concentration remains unclear. This review endeavours to summarize recent developments in this field.

Recent findings
Recent studies suggest that the molecular basis of severe HTG (polygenic susceptibility vs. rare pathogenic variants) can modulate the risk of acute pancreatitis independently of triglyceride level. Furthermore, a pancreatitis polygenic risk score has been developed and validated using data from the largest GWAS meta-analysis of acute pancreatitis published to date. In patients with severe HTG, a high polygenic susceptibility for pancreatitis was associated with a three-fold increased risk of acute pancreatitis compared with those with a lower polygenic risk score.

Summary
In the past months, there have been substantial advances in understanding the prediction of acute pancreatitis in patients with severe HTG. However, further efforts at developing risk-stratification strategies and predictive models may help identifying the patients who would benefit most from early and effective interventions to reduce the risk of pancreatitis, including treatment with APOC3 inhibitors.
Sexual Violence and Hazardous Drinking
Authors: Short Nicole A. , Shapiro Mary , Smit Tanya , McGrew Shelby J. , Zvolensky Michael J. , Vujanovic Anka A. 
Published: November 2024

Abstract
Sexual violence is associated with posttraumatic stress disorder (PTSD), but relatively less research has explored whether it is associated with hazardous drinking. PTSD symptoms may indirectly influence the association between sexual violence and hazardous alcohol use. This association may be moderated by gender. The aim of the current study was to cross-sectionally test whether sexual violence is indirectly associated with hazardous drinking through PTSD symptoms and explore whether gender moderates this association. Hypotheses were tested among 631 adults (M
age = 38, 56% men, 78.6% White) with probable PTSD and hazardous drinking who completed online self-report surveys. Results indicated sexual violence, compared with other trauma types, was associated with more severe hazardous drinking. There was a significant indirect effect of PTSD symptoms in this association. There was no evidence of a moderating effect of gender. PTSD symptoms may drive hazardous drinking among sexual violence survivors. Results also underscore associations between sexual violence and alcohol use, regardless of gender. Future work should continue to investigate these associations prospectively.