bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total and unprotonated (freebase) nicotine content in new types of oral ‘tobacco-free’ nicotine products
Authors: Tran Hang , Tyx Robert E , Valentin Liza , Mahoney Margaret , Stanfill Stephen , Watson Clifford H 
Published: November 2024

SignificanceNicotine-containing products, labelled as being ‘tobacco-free’ nicotine (TFN), are marketed to consumers as alternatives to conventional tobacco products. Little is known about these emerging products and their contents.MethodsMoisture, total nicotine and pH content were analysed in 70 commercially available TFN products, covering five different types (lozenges, chewing gum, loose leaf, toothpicks and pouches). The freebase nicotine was calculated using the measured pH values.ResultsTotal nicotine levels ranged from 0.822 to 31.5 mg/g. Nicotine levels were highest in nicotine pouches (1.41–8.11 mg/product) and lowest in toothpicks (1.19–1.57 mg/product). Nicotine levels in TFN loose leaf (1.26–9.16 mg/g) were comparable to conventional moist snuff. The pH ranged from pH 4.68 to 9.49 and per cent freebase nicotine ranged from 0.0453% to 96.7%. The freebase nicotine content was highest in nicotine pouches (2.15–16.8 mg/g) and lowest in lozenges (0.0004–0.349 mg/g). The majority of TFN products (91.4%) analysed were advertised to contain flavour components.ConclusionOverall, products advertised as higher strength were found to have higher nicotine content than products advertised as lower strength. The measured total nicotine content was either equal to or less than the level stated on the label, except for one product. Although TFN products may not contain tobacco lamina and may lack many harmful chemicals and carcinogens found in conventional smokeless products, freebase nicotine levels in the pouch products are elevated and could contribute to higher levels of addiction and other negative health effects.
Understanding Experiences of Diabetes Distress: A Systematic Review and Thematic Synthesis
Authors: Morales-Brown Louise Anne , Perez Algorta Guillermo , Salifu Yakubu 
Published: November 2024

Background: Diabetes distress is a common emotional issue for those living with diabetes, which has the potential to negatively impact well‐being, management behaviors, and HbA1c levels. These implications have led to diabetes distress becoming an important consideration in diabetes healthcare and management. Nonetheless, discussions remain ongoing on how to best conceptualize this experience. Recent research has attempted to enhance conceptualization by considering the underlying emotional mechanisms that may underpin the highly contextualized experience of diabetes distress. Qualitative insights can further add to these understandings; however, the research in this remit is yet to be systematically reviewed. This review therefore sought to add to the growing body of literature attempting to better conceptualize diabetes distress and the underlying mechanisms that may contribute to this experience. A secondary aim was to leverage this understanding to consider ways to improve patient–healthcare interactions.Methods: A qualitative systematic review and thematic synthesis was undertaken. Eligible studies were identified through PsycINFO, MEDLINE, CINAHL, and EMBASE databases from November 2020 to May 2021. Study quality was assessed using the McMaster Critical Review Form.Results: Nineteen papers were included in the review. The analysis resulted in seven descriptive themes which contributed to three analytical themes: (1) threatened autonomy, (2) sense of helplessness, and (3) negative sense of self. These results highlight that a major area underpinning experiences of diabetes distress is not feeling in control.Conclusions: Consideration should be given to how psychological factors, such as locus of control and learned helplessness, may constitute underlying mechanisms impacting emotional regulation in those experiencing diabetes distress. Clinicians should consider including and leading discussions around distress during appointments, as well as using approaches that promote patient autonomy and empowerment.
StreamLight Single‐Step Transepithelial Photorefractive Keratectomy (PRK) for Myopia and Myopic Astigmatism
Authors: Gunn David J. , Cox Rebecca A. 
Published: November 2024

Background: To report the refractive outcomes of StreamLight transepithelial photorefractive keratectomy (PRK).Methods: A retrospective case series was conducted which included a total of 205 eyes of 109 patients who underwent StreamLight transepithelial PRK using the Alcon Wavelight EX500 excimer laser. All eyes had myopia or myopic astigmatism, and the preoperative spherical equivalent (SEQ) ranged from −0.63D to −7.25D. The primary postoperative outcomes were UDVA, CDVA and subjective refraction measured at least 3 months postoperatively.Results: Postoperatively, 196 eyes (95.6%) had a UDVA of 20/20 or better. The mean SEQ was −0.05 ± 0.31D and 189 eyes (92.2%) were within ±0.50D of the target SEQ. The mean refractive astigmatism was −0.28 ± 0.27D, and 181 eyes (88.3%) had ≤ 0.50D of astigmatism. The mean safety and efficacy indices were 1.01 ± 0.08 and 0.97 ± 0.12, respectively. Eight eyes lost 1 line of CDVA. Six of these were noted to have significant dry eyes and 2 had corneal haze. No eye lost two or more lines of CDVA.Conclusions: StreamLight transepithelial PRK results in excellent refractive outcomes for myopia and myopic astigmatism.
Neoadjuvant Chemotherapy Shortens the cfDNA Telomere Length in Breast Cancer Patients
Authors: Peker Eyüboğlu İrem , Koca Sinan , Çelik Betül , Güllü Amuran Gökçe , Uğurlu M. Ümit , Alan Özkan , Akın Telli Tuğba , Yumuk Perran Fulden , Akkiprik Mustafa 
Published: November 2024

Introduction: Cancer is a genetic disease that affects people worldwide, and breast cancer is the most common cancer in women. Studies have been conducted on molecular parameters to predict tumor behavior and develop therapeutic strategies. Telomeres, which are at the end of chromosomes, have been studied for their relationship with breast cancer, but more research is needed to understand their role in the disease. Circulating‐free DNA (cfDNA) is DNA that is free in the bloodstream and is considered a promising target for early cancer detection, treatment response monitoring, and prognosis assessment. This study is aimed at comparing cfDNA telomere length of breast cancer patients and healthy individuals and analyzing the impact of neoadjuvant chemotherapy on telomere length in cfDNA.Materials and Methods: Blood samples were collected from 33 breast cancer patients undergoing neoadjuvant chemotherapy before and after treatment. The quantitative PCR method is used to measure the average telomere lengths.Results: This study found that the telomere length of cfDNA in breast cancer patients before and after treatment is significantly shorter than in the control group. Neoadjuvant chemotherapy is found to shorten the cfDNA telomere length, especially in the treatment‐responsive group.Conclusion: Our study suggests that telomere length in cfDNA may be a useful biomarker for predicting therapy response and possible reoccurrence of the disease in breast cancer patients.
The Effectiveness of Problem‐Based Learning in Reducing Work‐Related Musculoskeletal Problems Among Hospital Nurses: An Interventional Study
Authors: Modarresi Shahrzad , Rakhshani Tayebeh , Mehri Zahra , Kaydani Masoumeh , Rasouli Kahaki Zeinab , Rahgoshay Niloofar , Daneshmandi Hadi 
Published: November 2024

Background: Musculoskeletal disorders (MSDs) are common among nursing professionals and require effective management strategies. Implementing targeted training programs for nurses is a vital approach to reduce these problems.Aim: This study aimed to evaluate problem‐based learning (PBL) effectiveness in reducing work‐related musculoskeletal symptoms (WMSs) among nurses.Methods: Fifty Iranian nurses participated in this interventional study. Some data were collected by a demographic/occupational questionnaire and a Persian version of the Nordic Musculoskeletal Questionnaire (P‐NMQ). Some other was gathered by Rapid Entire Body Assessment (REBA) and PBL method.Results: The prevalence of WMSs during the last 12 months in the subjects was related to the lower back (76%), wrists/hands (70%), neck (64%), and knee (64%), respectively. The results showed that the prevalence of WMSs decreased significantly only in the subjects’ elbow region in the postintervention (p = 0.031). Although the prevalence decreased in the postintervention stage in other regions, this decrease was not statistically significant (p > 0.05).Conclusions: This study showed that the implementation of PBL could reduce the WMSs prevalence and the level of nurses’ exposure to risk factors for MSDs.
Impact of Depression on Cognitive Function and Phenoconversion to Neurodegenerative Diseases in Patients With Isolated REM Sleep Behavior Disorder
Authors: Moon Seock Hyeon , Hong Jung Kyung , Lee Minji , Kim Hak Hyeon , Yoon In-Young 
Published: November 2024

Background: This study was aimed at analyzing cognitive function and quantitative electroencephalogram (qEEG) in patients with isolated REM sleep behavior disorder (iRBD) based on the presence of depression and at evaluating the impact of depression on phenoconversion to neurodegenerative diseases.Methods: Individuals diagnosed with iRBD via polysomnography were included. Based on the presence of depression, patients were categorized into two groups. Neuropsychological tests and qEEG were conducted following the diagnosis of iRBD, and outcomes were compared between the two groups. Patients were regularly followed to monitor their phenoconversion status. Cox regression analysis was performed to assess the hazard ratio associated with depression.Results: Ninety iRBD patients (70% males) were included, with a median age of 66.3 years. Depression was identified in 26 (28.9%) of these patients. The depressed group showed significantly poorer performance only in color reading subtest of Stroop (p = 0.029) compared to the nondepressed group, showing reduced processing speed. In qEEG, relative gamma power (p = 0.034) and high gamma power (p = 0.020) in the parietal region were significantly higher in the depressed group than in the nondepressed group. Depression was associated with a hazard ratio of 3.32 for the risk of phenoconversion to neurodegenerative diseases in iRBD patients (p = 0.011).Conclusion: Depressive symptoms in iRBD patients should be closely monitored as they could aggravate cognitive dysfunction and increase the risk of phenoconversion to neurodegenerative diseases.
Efficacy of Step‐Down Therapy Using Vonoprazan for Symptomatic Mild Reflux Esophagitis
Authors: Ochiai Yorinari , Kikuchi Daisuke , Hoteya Shu 
Published: November 2024

Objective: Patient‐reported outcomes (PROs) are becoming pivotal in managing gastroesophageal reflux disease (GERD). Current Japanese guidelines for GERD recommend vonoprazan (VPZ) as a treatment option for mild reflux esophagitis (RE). However, it has been hypothesized that 4 weeks of VPZ 20 mg is not always necessary for mild RE if the treatment outcome is based on patient symptoms. This study is aimed at elucidating the efficacy of a new tapering therapeutic strategy (step‐down therapy) using VPZ for symptomatic mild RE based on PRO.Methods: This multicenter retrospective study examined VPZ’s efficacy for step‐down therapy between October 2021 and November 2022. Included were 63 consecutive patients from the outpatient clinics of Toranomon Hospital and Toranomon Hospital Kajigaya with symptoms associated with RE (frequency scale for the symptoms of GERD (FSSG) scores ≥ 8 points) and mild RE classified as the Los Angeles Classification Grade A or B. Step‐down therapy was defined as a treatment period of 28 days. VPZ 20 mg was administered as the initial treatment. Afterward, patients were allowed to step down to VPZ 10 mg if their symptoms improved, and VPZ could be discontinued if symptoms disappeared. If symptoms worsened, the dosage could be increased from 10 to 20 mg VPZ, or VPZ could be restarted at 20 mg after discontinuation.Results: The proportion of patients whose FSSG scores decreased by ≥ 3 points with step‐down therapy was 76.2% (48/63 patients). The median FSSG scores before and after step‐down therapy were 13 (range, 8–35) and 7 (range, 0–29), respectively (p < 0.01). Overall, 71.4% (45/63) of the patients stepped down from 20 to 10 mg VPZ, and 46% (29/63) of the patients discontinued VPZ.Conclusion: Step‐down therapy using VPZ may be a viable treatment option for symptomatic patients with mild RE.
The UBA1–STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade
Authors: Bao Yi , Cruz Gabriel , Zhang Yuping , Qiao Yuanyuan , Mannan Rahul , Hu Jing , Yang Fan , Gondal Mahnoor , Shahine Miriam , Kang Sarah , Mahapatra Somnath , Chu Alec , Choi Jae Eun , Yu Jiali , Lin Heng , Miner Stephanie J. , Robinson Dan R. , Wu Yi-Mi , Zheng Yang , Cao Xuhong , Su Fengyun , Wang Rui , Hosseini Noshad , Cieslik Marcin , Kryczek Ilona , Vaishampayan Ulka , Zou Weiping , Chinnaiyan Arul M. 
Published: November 2024

Abstract
How cancer cells escape immune surveillance and resist immune checkpoint blockade (ICB) remains to be fully elucidated. By screening candidate genes frequently gained in cancer, we identified expression of ubiquitin-like modifier-activating enzyme 1 (UBA1) as being the most negatively correlated with signatures related to effector CD8+ T cells. High UBA1 expression was strongly predictive of treatment resistance and poor survival in ICB cohorts. Functional studies revealed that UBA1 mediated immune escape to promote tumor growth. Immune profiling further showed that Uba1 overexpression or depletion markedly decreased or increased functional intratumoral CD8+ T cells, respectively. Importantly, a selective UBA1 inhibitor, TAK-243, significantly synergized with ICB in multiple syngeneic models. Mechanistically, depletion or inactivation of the UBA1–STUB1 axis stabilized a key IFN pathway component (JAK1), enhanced IFN signaling, and elevated key immune modulators, including CXCL9, CXCL10, and MHC class I. Our study warrants clinical evaluation of the combination of UBA1 inhibitors and ICB.

Significance:
Our study reveals UBA1 as a predictive biomarker for clinical outcomes in ICB cohorts, mediating cancer immune evasion and ICB resistance. We further highlight JAK1 stabilization as a key mechanism of UBA1 inhibition and nominate the UBA1–STUB1 axis as an immuno-oncology therapeutic target to improve the efficacy of ICB.
Identification of ncRNA Biomarkers in Non–Small Cell Lung Cancer to Address Racial Disparities
Authors: Gao Lu , Dhilipkannah Pushpa , Jiang Feng 
Published: November 2024

Abstract
Lung cancer significantly impacts mortality, with African Americans (AA) showing higher rates than White Americans (WA). ncRNAs play a crucial role in lung tumorigenesis. To identify ncRNA biomarkers associated with racial disparities in lung cancer, we used droplet digital PCR to examine 93 lung cancer–associated ncRNAs in plasma and sputum samples from participants of AA and WA backgrounds, including 118 patients and 92 cancer-free smokers. In the AA population, plasma showed differential expression of 10 ncRNAs, whereas sputum revealed four ncRNAs when comparing patients with lung cancer to the control group. In the WA population, the plasma displayed 11 ncRNAs, and the sputum had five ncRNAs showing differential expression between patients with lung cancer and the control group. For AAs, we identified a three-ncRNA panel (plasma miRs–147b, 324-3p, and 422a) for diagnosing lung cancer in AAs with 86% sensitivity and 89% specificity. For WAs, a four-ncRNA panel comprising sputum miR-34a-5p and plasma miRs–103-3p, 126-3p, and 205-5p was developed, achieving 88% sensitivity and 87% specificity. These panels remained effective across various stages and types of lung tumors and were validated in an independent cohort of 56 patients and 72 controls. Ethnicity-related ncRNA signatures hold promise as biomarkers for tackling racial disparities in patients with lung cancer.

Significance:
This study identifies ethnicity-related ncRNA biomarkers that differentiate lung cancer in AAs and WAs, offering diagnostic panels with high sensitivity and specificity. These findings provide a promising approach to addressing racial disparities in lung cancer detection and improving early diagnosis across diverse populations.
VEGFC Overexpression in Kidney Progenitor Cells Is a Model of Renal Lymphangiectasia—Brief Report
Authors: Donnan Michael D. , Deb Dilip K. , Dalal Vidhi , David Valentin , Procissi Daniele , Quaggin Susan E. 
Published: November 2024

BACKGROUND:
Lymphangiogenesis is believed to be a protective response in the setting of multiple forms of kidney injury and mitigates the progression of interstitial fibrosis. To augment this protective response, promoting kidney lymphangiogenesis is being investigated as a potential treatment to slow the progression of kidney disease. As injury-related lymphangiogenesis is driven by signaling from the receptor VEGFR3 (vascular endothelial growth factor receptor 3) in response to the cognate growth factor VEGF (vascular endothelial growth factor)-C released by tubular epithelial cells, this signaling pathway is a candidate for future kidney therapeutics. However, the consequences to kidney development and function to targeting this signaling pathway remain poorly defined.

METHODS:

We generated a new mouse model expressing
Vegfc
under regulation of the nephron progenitor Six2Cre driver strain (
Six2Vegfc
). Mice underwent a detailed phenotypic evaluation. Whole kidneys were processed for histology and 3-dimensional imaging.

RESULTS:

Six2Vegfc
mice had reduced body weight and kidney function compared with littermate controls.
Six2Vegfc
kidneys demonstrated large peripelvic fluid-filled lesions with distortion of the pelvicalcyceal system which progressed in severity with age. Three-dimensional imaging showed a 3-fold increase in total cortical vascular density. Histology confirmed a substantial increase in LYVE1+ (lymphatic vessel endothelial hyaluronan receptor-1)/PDPN+ (podoplanin)/VEGFR3+ lymphatic capillaries extending alongside EMCN+ (endomucin) peritubular capillaries. There was no change in EMCN+ peritubular capillary density.

CONCLUSIONS:

Kidney lymphatic density was robustly increased in the
Six2Vegfc
mice. There were no changes in peritubular blood capillary density despite these endothelial cells also expressing VEGFR3. The model resulted in malformation of the lymphatic hilar plexus, resulting in severe hydronephrosis that resembled a human condition termed renal lymphangiectasia. This study defines the vascular consequences of augmenting VEGFC signaling during kidney development and provides new insight into human renal lymphatic malformations.
Abstract 4138949: Type 2 Diabetes is Not a Coronary Artery Disease Risk Equivalent: Longterm Results from a Prospective Cohort Study on Patients Who Underwent Coronary Angiography
Authors: Plattner Thomas , Larcher Barbara , Mader Arthur , Vonbank Alexander , Leiherer Andreas , Muendlein Axel , Drexel Heinz , Saely Christoph H 
Published: November 2024

Type 2 Diabetes (T2DM) and pre-existing coronary artery disease (CAD) are strong and independent risk factors for cardiovascular events, and data from large cohort studies suggest that the cardiovascular risk conferred by T2DM in the absence of CAD is equivalent to that conferred by CAD in the absence of T2DM. However, because the presence of CAD in these studies was defined clinically rather than by visualization, unrecognized subclinical CAD in T2DM patients may have biased results.
We therefore prospectively investigated patients with T2DM and non-diabetic subjects in whom the baseline CAD state was diagnosed angiographically. We recorded cardiovascular events over a follow-up period of 22 years in a large cohort of 1819 patients undergoing coronary angiography for the evaluation of established or suspected stable CAD.
From our patients, 595 had neither significant CAD nor T2DM (CAD-/T2DM-), 171 had T2DM but not significant CAD (CAD-/T2DM+), 701 had significant CAD but not T2DM (CAD+/T2DM-) and 352 had both T2DM and significant CAD (CAD+/T2DM+). The incidence of cardiovascular events was lowest in CAD-/T2DM- patients (24.7%). Compared to this group it was significantly higher in CAD-/T2DM+ patients (36.1%; p<0.001) and in CAD+/T2DM- patients (50.8%; p<0.001) and highest (p=0.001) in CAD+/T2DM+ patients, in whom it was higher than in CAD-/T2DM+ (p<0.001) or CAD+/T2DM- (p=0.001) patients. Importantly, CAD+/T2DM- patients were at a significantly higher risk of cardiovascular events than CAD-/T2DM+ patients (p<0.001). In Cox regression analysis the risk increase conferred by CAD was higher (adjusted (HR 2.35 [1.92-2.89]; p<0.001) than that conferred by T2DM (adjusted HR 1.54 [1.33-1.78]; p< 0.001).
From our long term results we conclude that angiographically diagnosed CAD is a stronger predictor of future cardiovascular events than T2DM. T2DM is not a CAD risk equivalent.
Abstract 4139444: Benign Metastasizing Leiomyoma: A Challenging Case with Multifocal Involvement in the Heart, Liver, and Uterus
Authors: Vu Huong , Bui Hanh , Huynh Hai , Vo Duc , Minh Le Huu Nhat , Nguyen Hien 
Published: November 2024

Case Presentation:
A 39-year-old Southeast Asian female presented with fatigue and exertional dyspnea. She underwent a myomectomy four years ago. Examination showed vital signs within normal limits, except for an SpO2 of 87%. Blood tests indicated microcytic hypochromic anemia and elevated D-Dimer levels of 1479 ng/mL.

A transthoracic echocardiogram revealed a large mass occupying almost the entire right atrium, extending into the inferior vena cava. A CT scan showed a large, low attenuation, and minimally enhanced mass extending from the right atrium into the inferior vena cava and right hepatic vein, possibly invading segments VII-VIII of the liver (Figure 1). Abdominal CT and MR images revealed multiple degenerating uterine fibroids, bilateral dilated uterine tubes, and mild right hydronephrosis (Figure 2).
The patient underwent surgical removal of the cardiac mass under general anesthesia with extracorporeal circulation and hypothermia. Pathological examination confirmed a benign tumor characterized by bundles of smooth muscle cells (Figure 3). Immunohistochemical staining with Actin (+), Progesterone receptor (+), Desmin (+), Ki67 (+) was consistent with a diagnosis of benign metastasizing leiomyoma (BML) of the heart. Subsequently, elective hysterectomy and bilateral salpingo-oophorectomy were performed.

Discussion:
Although rare, uterine leiomyoma can exhibit metastatic behavior, disseminating to extraneous anatomical sites. BML should be considered in the differential diagnosis when patients present with an atypical cardiac mass and have a history of uterine leiomyoma, myomectomy, or hysterectomy.

BML of the heart is an exceptionally rare condition, predominantly affecting middle-aged women who have undergone hysterectomy or myomectomy. While BML commonly occurs in pre-menopausal patients and shares a potentially similar mechanism with endometriosis, as indicated by its response to estrogen-blocking agents, the occurrence of BML in post-menopausal women suggests the involvement of other contributing factors.
Multiple imaging modalities play a significant role in the diagnosis and preparation for surgical management.