bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory‐swallow patterning and oropharyngeal swallowing impairment in patients undergoing evaluation for lung transplant
Authors: Graham Kahla , Reedy Erin L. , Lee Jungwha Julia , Norton Elizabeth Spencer , Arunachalam Ambalavanan , Tomic Rade , Martin‐Harris Bonnie 
Published: September 2024

AbstractBackgroundAlthough swallowing impairment is prevalent following lung transplantation, baseline respiratory and swallowing characteristics are often overlooked. Respiratory disease processes may predispose lung transplant candidates to altered respiratory‐swallow patterning and swallowing impairment.MethodsThis cross‐sectional study included patients referred for a Modified Barium Swallow Study during lung transplant evaluation. Swallowing impairment was measured using the Modified Barium Swallow Impairment Profile and Penetration‐Aspiration Scale. Respiratory plethysmographic signals synchronized with videofluoroscopy were analyzed to determine phase patterning, pause duration, and rate. Mixed‐effects logistic regression was used to identify linkages between respiratory and swallowing measures.Key ResultsFifty patients were included and demonstrated delayed swallow initiation (49/50), oral residue (37/50), incomplete pharyngoesophageal segment opening (35/50), and esophageal retention (43/50). Airway invasion occurred infrequently (10/50). Atypical respiratory patterning was significantly associated with impairment in pharyngeal swallow initiation (OR [95% CI] = 1.76 [1.16, 2.68], p = 0.009), laryngeal elevation (OR [95% CI] = 1.45 [1.01, 2.07], p = 0.044), and laryngeal vestibular closure (OR [95% CI] = 2.57 [1.48, 4.46], p < 0.001). Increased pause duration was associated with impaired initiation (OR [95% CI] = 2.24 [1.20, 4.16], p = 0.011), laryngeal elevation (OR [95% CI] = 1.18 [1.03, 1.36], p = 0.018), laryngeal closure (OR [95% CI] = 1.28 [1.9, 1.50], p = 0.003), and tongue base retraction (OR [95% CI] = 1.33 [1.13, 1.56], p < 0.001).Conclusions & InferencesPatients undergoing evaluation for lung transplant demonstrated impaired swallowing and phase patterning. Preliminary findings implicate the need for further evaluation of respiratory‐swallow coordination and its potential role in swallowing impairment before and after lung transplantation.
Preventive and reparative effects of low‐level laser therapy on orthodontically induced inflammatory root resorption—An animal study
Authors: Xu Bowen , Du Rina , Bai Linna , Yang Kai 
Published: September 2024

AbstractBackgroundOrthodontically induced inflammatory root resorption (OIIRR) is one of the most important side effects of orthodontic treatment. Low‐level laser therapy (LLLT) is a useful way to reduce the orthodontic treatment duration and may have some effect on preventing and repairing OIIRR. However, the specific effects of LLLT on OIIRR remain unknown.ObjectiveOur research aimed to evaluate the Dentin Sialophosphoprotein (DSPP) expression level and root resorption volume during treatment and retention to explore the role of LLLT in preventing and repairing OIIRR.MethodsThirty‐seven 6‐week‐old male Sprague–Dawley rats were selected to establish an OIIRR model; the rats were divided into Group B (blank), Group F (force), Group F(LLLT) (force and LLLT), Group F+R (force and retention) and Group F+R(LLLT) (force, retention and LLLT). The root resorption volume of the distal buccal root and mesial root in the maxillary left first molar was calculated by micro‐CT, and the DSPP expression level on the compression side of the periodontal ligament was analysed by immunohistochemical staining.ResultsThe resorption volume in Group F was greater than that in Group F(LLLT). For the mesial root, the volume in Group F was greater than that in Groups F+R and F+R(LLLT). For the distal buccal root, the volume in Groups F and F+R was greater than that in Group F+R(LLLT). The DSPP level in Group F(LLLT) was greater than that in Group F and there was no difference between Groups F+R and F+R(LLLT).ConclusionsLLLT has a certain preventive effect and a limited reparative effect on OIIRR in rats.
Left‐bundle branch optimized CRT implantation in a patient with persistent left superior vena cava
Authors: Gul Enes Elvin , Sodikov Jamshid , Sertdemir Ahmet Lutfu , Yakubov Akmal 
Published: September 2024

AbstractPersistent left superior vena cava (PLSVC) is one of the anatomical variations, which can make device implantation more challenging and lead to incorrect lead placement, dislodgement, and procedure failure. Conduction system pacing (CSP) can be an alternative to traditional CRT implantation. Herein, we describe a brief case report of successful LBBAP‐optimized CRT (LOT‐CRT) via an innominate vein in a patient with PLSVC.
Dermatoscopic features of vulvar lichen sclerosus in children: A retrospective study
Authors: Han Yuyang , Liu Runtao , Li Yuanjun 
Published: September 2024

AbstractObjectivesTo explore the dermoscopic features of lichen sclerosus in different parts of the external genitalia in children.MethodsA retrospective analysis of the dermoscopic features of 42 female children with vulvar lichen sclerosus treated in the Department of Dermatology of Shanxi Children's Hospital from January 2020 to May 2023.ResultsAmong the 42 female children, aged 3–14 years (mean: 7.24 ± 2.43 years), the duration of vulvar lichen sclerosus ranged from 3 months to 2 years (mean: 9.83 ± 4.93 months). Clinical lesions occurred in the labia minora in 18 cases (42.9%), labia majora in 38 cases (90.5%), posterior fourchette in 36 cases (85.7%), perianal area in 13 cases (31.0%), anterior fourchette in 17 cases (40.5%), clitoris in seven cases (16.7%), and interlabial sulcus in 11 cases (26.2%). Dermoscopic findings common in the labia majora included follicular keratotic plugs, cloverleaf‐like structures, comedo‐like openings, and linear vessels (p < .05); however, purple–red globules and patches and white linear streaks were more common in the posterior fourchette (p < .05), whereas dotted vessels were more common in the labia minora (p < .05).ConclusionsCommon dermoscopic findings in pediatric vulvar lichen sclerosus were yellow‐white structureless areas, white linear streaks, follicular keratotic plugs, and cloverleaf‐like structures; yellow‐white structureless areas and white linear streaks showed the highest specificity. The dermoscopic findings varied among different affected areas, which provides a basis for further understanding of the characteristics of different sites of vulvar lichen sclerosus in the pediatric population.
Trends in adverse effects of medical treatment in Paediatric populations in the United States: A global burden of disease study, 2000–2019
Authors: Fujiwara Shintaro , Leibovitch Emily , Harada Ko , Nishimura Yoshito , Woo Russell , Otsuka Fumio , Bhagavathula Akshaya Srikanth 
Published: September 2024

AbstractBackgroundAdverse effects of medical treatment (AEMT) pose significant risks to paediatric patients. However, the mortality trends associated with AEMT in this population have been unclear.ObjectiveWe aimed to clarify the trends in the incidence, disability‐adjusted life years (DALYs) and mortality rates of AEMT for children in the US from 2000 to 2019.MethodsData were retrieved from the Global Burden of Disease study 2019. We estimated age‐standardized incidence, DALYs and mortality rates of paediatric AEMT per 100,000 children in the US using a Bayesian meta‐regression model. We also analysed incidence, DALYs and mortality in different age groups, and employed Joinpoint regression models to assess the age‐ and sex‐specific trends.ResultsThe number of deaths due to AEMT in children, the number of cases, and DALYs were 105.1, 551,076 and 145,555 in 2019, decreased by 37.5%, 6% and 28% from those in 2000, respectively. Age‐standardized mortality rates decreased across all age groups, while the incidence increased across all age groups with an average annual percentage change (AAPC) of 2.2% in those children <1 year and 4.5% in 5–9 years of age. The increases in DALYs over time was higher in children aged 1–4 years (AAPC: 0.51, 95% CI: 0.47, 0.62) and 5–9 years (AAPC: 0.33, 95% CI: 0.15, 0.50), with the 1–4 year age group being the highest.ConclusionThe study reveals declining AEMT mortality but rising incidence and DALYs, emphasizing a disproportionate burden in <1, 1–4 and 5–9 years. To develop effective mitigation strategies, future research is warranted to identify the causes of increased AEMT in children, especially young males.
Therapeutic potential of silkworm sericin in wound healing applications
Authors: Prakash Monika , Mathikere Naganna Chandraprabha , Radhakrishnan Vivek , Somayaji Prathik , Sabu Leah 
Published: September 2024

AbstractChronic wounds are characterised by an imbalance between pro and anti‐inflammatory signals, which result in permanent inflammation and delayed re‐epithelialization, consequently hindering wound healing. They are associated with bacterial infections, tissue hypoxia, local ischemia, reduced vascularization and MMP‐9 upregulation. The global prevalence of chronic wounds has been estimated at 40 million in the adult population, with an alarming annual growth rate of 6.6%, making it an increasingly significant clinical problem. Sericin is a natural hydrophilic protein obtained from the silkworm cocoon. Due to its biocompatibility, biodegradability, non‐immunogenicity and oxidation resistance, coupled with its excellent affinity for target biomolecules, it holds great potential in wound healing applications. The silk industry discards 50,000 tonnes of sericin annually, making it a readily available material. Sericin increases cell union sites and promotes cell proliferation in fibroblasts and keratinocytes, thanks to its cytoprotective and mitogenic effects. Additionally, it stimulates macrophages to release more therapeutic cytokines, thus improving vascularization. This review focuses on the biological properties of sericin that contribute towards enhanced wound healing process and its mechanism of interaction with important biological targets involved in wound healing. Emphasis is placed on diverse wound dressing products that are sericin based and the utilisation of nanotechnology to design sericin nanoparticles that aid in chronic wound management.
Properties of Central Regions of the Dark Matter Halos in the Model with a Bump in the Power Spectrum of Density Perturbations
Authors: Eroshenko Yu. N. , Lukash V. N. , Mikheeva E. V. , Pilipenko S. V. , Tkachev M. V. 
Published: September 2024

A surprisingly large number of galaxies with masses of ~109–1010$${{M}_{ \odot }}$$ at redshifts of $$z \geqslant 9$$ are discovered with the James Webb Space Telescope. A possible explanation for the increase in the mass function can be the presence of a local maximum (bump) in the power spectrum of density perturbations on the corresponding scale. In this paper, it is shown that simultaneously with the growth of the mass function, galaxies from the bump region must have a higher density (compactness) compared to cosmological models without a bump. These more compact galaxies have been partially included in larger galaxies and have been subjected to tidal gravitational disruption. They have been less destructed than “ordinary” galaxies of the same mass, and some of them could survive to z = 0 and persist on the periphery of some galaxies. The formation and evolution of compact halos in a cube with a volume of (47 Mpc)3 with (1024)3 dark matter particles in the redshift range from 120 to 0 have been numerically simulated and observational implications of the presence of such galaxies in the current Universe have been discussed.
An examination of exercise intensity and its impact on the acute release of irisin across obesity status: a randomized controlled crossover trial
Authors: Rioux Brittany V. , Paudel Yadab , Thomson Amy M. , Peskett Logan E. , Sénéchal Martin 
Published: September 2024

Limited data exist regarding the impact of exercise intensity on irisin release and its association with insulin sensitivity in individuals of differing obesity status. The objective of this study was to investigate the impact of exercise intensity on the acute release of irisin in healthy-weight individuals and individuals with obesity, and whether irisin release during acute exercise was associated with greater insulin sensitivity across obesity status. A randomized controlled crossover study was conducted on 26 non-overweight/obese (non-OW/OB) (BMI: 22.2 ± 1.5  kg/m2) and 26 overweight/obese (OW/OB) (BMI: 33.9 ± 6.5  kg/m2) adults who performed an acute bout of moderate-intensity continuous training (MICT), high-intensity interval training (HIIT), and rest. Irisin was quantified via ELISA and western blotting, and insulin sensitivity (Si) was estimated using the Matsuda index. OW/OB displayed a significantly lower level of circulating irisin and protein expression compared to non-OW/OB ( p < 0.01). Insulin sensitivity was positively correlated with irisin release during MICT and HIIT in non-OW/OB (all p < 0.05), but not in OW/OB. Regarding irisin expression, non-OW/OB with high Si had a 2.03-fold ( p < 0.05) increase during HIIT, while OW/OB with high Si had only a 1.54-fold increase ( p < 0.05). These results suggest that irisin is released differently according to obesity status and varying exercise intensities. OW/OB individuals have a blunted irisin response to acute exercise and lower baseline irisin concentrations compared to non-OW/OB individuals. Although exercise stimulates irisin release in non-OW/OB individuals, only a greater exercise intensity stimulates irisin release in OW/OB individuals. These findings are clinically relevant, as irisin is associated with greater insulin sensitivity. This trial was registered at clinicaltrials.gov (NCT03514238).
Designing Rigorous and Efficient Clinical Utility Studies for Early Detection Biomarkers
Authors: Zheng Yingye , Wagner Paul D. , Singal Amit G. , Hanash Samir M. , Srivastava Sudhir , Huang Ying , Zhao Ying-Qi , Chari Suresh T. , Marquez Guillermo , Etizioni Ruth , Marsh Tracey L. , Feng Ziding 
Published: September 2024

Abstract
Before implementing a biomarker in routine clinical care, it must demonstrate clinical utility by leading to clinical actions that positively affect patient-relevant outcomes. Randomly controlled early detection utility trials, especially those targeting mortality endpoint, are challenging due to their high costs and prolonged duration. Special design considerations are required to determine the clinical utility of early detection assays. This commentary reports on discussions among the National Cancer Institute’s Early Detection Research Network investigators, outlining the recommended process for carrying out single-organ biomarker-driven clinical utility studies. We present the early detection utility studies in the context of phased biomarker development. We describe aspects of the studies related to the features of biomarker tests, the clinical context of endpoints, the performance criteria for later phase evaluation, and study size. We discuss novel adaptive design approaches for improving the efficiency and practicality of clinical utility trials. We recommend using multiple strategies, including adopting real-world evidence, emulated trials, and mathematical modeling to circumvent the challenges in conducting early detection utility trials.
Lung Microbial and Host Genomic Signatures as Predictors of Prognosis in Early-Stage Adenocarcinoma
Authors: Tsay Jun-Chieh J. , Darawshy Fares , Wang Chan , Kwok Benjamin , Wong Kendrew K. , Wu Benjamin G. , Sulaiman Imran , Zhou Hua , Isaacs Bradley , Kugler Matthias C. , Sanchez Elizabeth , Bain Alexander , Li Yonghua , Schluger Rosemary , Lukovnikova Alena , Collazo Destiny , Kyeremateng Yaa , Pillai Ray , Chang Miao , Li Qingsheng , Vanguri Rami S. , Becker Anton S. , Moore William H. , Thurston George , Gordon Terry , Moreira Andre L. , Goparaju Chandra M. , Sterman Daniel H. , Tsirigos Aristotelis , Li Huilin , Segal Leopoldo N. , Pass Harvey I. 
Published: September 2024

Abstract

Background:
Risk of early-stage lung adenocarcinoma recurrence after surgical resection is significant, and the postrecurrence median survival is approximately 2 years. Currently, there are no commercially available biomarkers that predict recurrence. In this study, we investigated whether microbial and host genomic signatures in the lung can predict recurrence.

Methods:
In 91 patients with early-stage (stage IA/IB) lung adenocarcinoma with extensive follow-up, we used 16s rRNA gene sequencing and host RNA sequencing to map the microbial and host transcriptomic landscape in tumor and adjacent unaffected lung samples.

Results:
Of 91 subjects, 23 had tumor recurrence over 5-year period. In tumor samples, lung adenocarcinoma recurrence was associated with enrichment in Dialister and Prevotella, whereas in unaffected lung samples, recurrence was associated with enrichment in Sphingomonas and Alloiococcus. The strengths of the associations between microbial and host genomic signatures with lung adenocarcinoma recurrence were greater in adjacent unaffected lung samples than in the primary tumor. Among microbial–host features in the unaffected lung samples associated with recurrence, enrichment in Stenotrophomonas geniculata and Chryseobacterium was positively correlated with upregulation of IL2, IL3, IL17, EGFR, and HIF1 signaling pathways among the host transcriptome. In tumor samples, enrichment in Veillonellaceae (Dialister), Ruminococcaceae, Haemophilus influenzae, and Neisseria was positively correlated with upregulation of IL1, IL6, IL17, IFN, and tryptophan metabolism pathways.

Conclusions:
Overall, modeling suggested that a combined microbial/transcriptome approach using unaffected lung samples had the best biomarker performance (AUC = 0.83).

Impact:
This study suggests that lung adenocarcinoma recurrence is associated with distinct pathophysiologic mechanisms of microbial–host interactions in the unaffected lung rather than those present in the resected tumor.
Searching for the Scale-Able Weight Loss Intervention: Can One Size Fit All? Lessons to Be Learned from the EQUAL Trial
Authors: Moore Travis R. , Demark-Wahnefried Wendy 
Published: September 2024

AbstractOverweight and obesity affect 71.2% of adults in the United States, with cancer survivors not far behind at 70.3%. Subgroups such as those diagnosed with acute lymphoblastic leukemia (ALL) face even greater challenges. The Exercise and Quality Diet after Leukemia (EQUAL) trial sought to address weight management issues among ALL survivors by implementing a remotely delivered weight loss intervention, leveraging the previously proven Practice-based Opportunities for Weight Reduction (POWER) program. Despite a strong foundation and design, the EQUAL trial yielded null results. Key differences in study populations and intervention contexts between the EQUAL and POWER trials, such as the lack of primary care physician involvement in EQUAL, contributed to these outcomes. EQUAL’s failure to meet its accrual target and poor adherence among participants highlighted challenges in engaging this unique population. Contrary to EQUAL’s conclusions, evidence from other studies supports the efficacy of remote interventions for weight loss among cancer survivors. The lack of qualitative assessment among ALL survivors and key integration to inform intervention adaptations undermined EQUAL’s impact. However, EQUAL’s impressive retention rate offers valuable insights. Lessons from EQUAL underscore the need for well-fitted, remotely delivered interventions and the importance of thoughtfully adapted and tailored approaches to specific survivor populations.See related article by Fiedmann et al., p. 1158
A Phase II Study of Atezolizumab, Pertuzumab, and High-Dose Trastuzumab for Central Nervous System Metastases in Patients with HER2-Positive Breast Cancer
Authors: Giordano Antonio , Kumthekar Priya U. , Jin Qingchun , Binboga Kurt Busem , Ren Siyang , Li Tianyu , Leone Jose Pablo , Mittendorf Elizabeth A. , Pereslete Alyssa M. , Sharp Laura , Davis Raechel , DiLullo Molly , Tayob Nabihah , Mayer Erica L. , Winer Eric P. , Tolaney Sara M. , Lin Nancy U. 
Published: September 2024

Abstract

Purpose:
Patients with HER2-positive breast cancer brain metastases have few effective systemic therapy options. In a prior study, pertuzumab with high-dose trastuzumab demonstrated a high clinical benefit rate (CBR) in the central nervous system (CNS) in patients with brain metastases. The current trial evaluated whether the addition of atezolizumab to this regimen would produce further improvements in CNS response.

Patients and Methods:
This was a single-arm, multicenter, phase II trial of atezolizumab, pertuzumab, and high-dose trastuzumab for patients with HER2-positive breast cancer brain metastases. Participants received atezolizumab 1,200 mg i.v. every 3 weeks, pertuzumab (loading dosage 840 mg i.v., then 420 mg i.v. every 3 weeks), and high-dose trastuzumab (6 mg/kg i.v. weekly for 24 weeks, then 6 mg/kg i.v. every 3 weeks). The primary endpoint was CNS overall response rate per Response Assessment in Neuro-Oncology Brain Metastases criteria. Key secondary endpoints included CBR, overall survival, and safety and tolerability of the combination.

Results:
Among 19 enrolled participants, two had a confirmed intracranial partial response for a CNS overall response rate of 10.5% (90% confidence interval, 1.9%–29.6%). The study did not meet the prespecified efficacy threshold and was terminated early. The CBR was 42.1% at 18 weeks and 31.6% at 24 weeks. Seven patients (36.8%) required a dose delay or hold, and the most frequent any-grade adverse events were diarrhea (26.3%) and fatigue (26.3%).

Conclusions:
The addition of atezolizumab to pertuzumab plus high-dose trastuzumab does not result in improved CNS responses in patients with HER2-positive breast cancer brain metastases.
Genomic Profiling and Immune Phenotyping of Neuroendocrine Bladder Cancer
Authors: Zang Jingyu , Shahatiaili Akezhouli , Cai Mei-Chun , Jin Di , Shen Peiye , Qian Lei , Zhang Lu , Zhang Tianxiang , Wu Yuchen , Yang Fan , Wu Zheng , Hou Yanli , Bai Yongrui , Xia Jun , Cheng Liang , Zhang Ruiyun , Zhuang Guanglei , Chen Haige 
Published: September 2024

Abstract

Purpose:
Neuroendocrine bladder cancer (NEBC) poses a formidable clinical challenge and attracts keen interests to explore immunotherapy as a viable treatment option. However, a comprehensive immunogenomic landscape has yet to be thoroughly investigated.

Experimental Design:
Leveraging a long-term cohort of natural NEBC cases, we employed a multimodal approach integrating genomic (n = 19), transcriptomic (n = 3), single-cell RNA sequencing (n = 1), and IHC analyses (n = 34) to meticulously characterize the immunogenicity and immunotypes of primary NEBC tumors. Information on clinical, pathologic, medical imaging, and treatment aspects was retrospectively retrieved and analyzed.

Results:
Our study unveiled that despite a considerable mutational burden, NEBC was typically immunologically inactive, as manifested by the “immune-excluded” or “immune-desert” microenvironment. Interestingly, a subset of mixed NEBC with concurrent urothelial bladder cancer histology displayed an “immune-infiltrated” phenotype with prognostic relevance. When compared with urothelial bladder cancer, NEBC lesions were distinguished by a denser cellular composition and augmented peritumoral extracellular matrix, which might collectively impede lymphatic infiltration. As a result, single-agent immune checkpoint inhibitors demonstrated limited efficacy against NEBC, whereas pharmacologic immunostimulation with combination chemotherapy conferred a more favorable response.

Conclusions:
These new insights derived from genomic profiling and immune phenotyping pave the way for rational immunotherapeutic interventions in patients with NEBC, with the potential to ultimately reduce mortality from this otherwise fatal disease.