bluuebunny/crossref_metadata_2025_split huggingface dataset:
Radical overlapping intravelar veloplasty during primary cleft palate repair results in decreased secondary speech surgery
Authors: Podolsky Dale J , Fischbach Simone , Wong Riff Karen WY , Saggaf Moaath , Klaiman Paula , Fisher David M 
Published: September 2024

Background:
There is growing evidence that performing a radical intravelar veloplasty (IVV) improves speech outcomes. The aim of this study was to determine the impact of a radical IVV during primary palatoplasty on the rate of secondary speech surgery.

Methods:
This is a retrospective review of primary palatoplasty using an IVV performed by a single surgeon from the year 2000 to 2023. In 2008, the surgeon changed technique to involve a more radical IVV. The radical overlapping IVV involves release of the palatopharyngeus from the posterior hard palate and from the nasal component of the tensor veli palatini, release of the levator veli palatini to the levator tunnel, and overlapping of the palatopharyngeus-levator unit across the midline after retro-positioning. This separated the patients into a before and after technique change group. The rate of secondary speech surgery was compared between the two time periods.

Results:
An IVV was performed during straight line repairs 333 and 272 times during the first and second time periods, respectively. The second radical overlapping IVV group had significantly (p<0.05) less secondary speech surgery procedures at 43 (15.81%) compared to 83 (24.92%) amongst the first conservative IVV group (p<0.05).

Conclusions:
Precise anatomical dissection, extensive release, retro-positioning and overlap of the velar musculature during IVV results in significantly less secondary speech surgery.
Diagnostic Accuracy of Ultrasound Guidance in Transthoracic Needle Biopsy
Authors: Lemieux Simon , Pinard Lorence , Marchand Raphaël , Kali Sonia , Altmayer Stephan , Mai Vicky , Provencher Steeve 
Published: September 2024

Purpose:
To perform a systematic review and meta-analysis of relevant studies to assess the diagnostic accuracy and safety outcomes of ultrasound (US)-guided transthoracic needle biopsy (TTNB) for peripheral lung and pleural lesions.

Materials and Methods:
A search was performed through Medline, Embase, Web of Science, and Cochrane Central from inception up to September 23, 2022 for diagnostic accuracy studies reporting US-guided TTNB (Prospero registration: CRD42021225168). The primary outcome was diagnostic accuracy, which was assessed by sensitivity, specificity, likelihood ratios (LR), and diagnostic odds ratio. Sensitivity and subgroup analyses were performed to evaluate inter-study heterogeneity. The secondary outcome was the frequency of complications. Random-effects models were used for the analyses. The risk of bias and the applicability of the included studies were assessed using the QUADAS-2 tool. Publication bias was assessed by testing the association between the natural logarithm of the diagnostic odds ratio and the effective sample size.

Results:
Of the 7841 citations identified, 83 independent cohorts (11,767 patients) were included in the analysis. The pooled sensitivity of US-TTNB was 88% (95% CI: 86%-91%, 80 studies). Pooled specificity was 100% (95% CI: 99%-100%, 72 studies), resulting in positive LR, negative LR, and diagnostic odds ratio of 946 (−743 to 2635), 0.12 (0.09 to 0.14), and 8141 (1344 to 49,321), respectively. Complications occurred in 4% (95% CI: 3%-5%) of the procedures, with pneumothorax being the most frequent (3%; 95% CI: 2%-3%, 72 studies) and resulting in chest tube placement in 0.4% (95% CI: 0.2%-0.7%, 64 studies) of the procedures.

Conclusions:
US-TTNB is an effective and safe procedure for pleural lesions and peripheral lung lesions.
Effect of Surgical Timing to Dental Health in Secondary Alveolar Bone Grafting: Three-Dimensional Outcomes
Authors: Kwon Donghwan , Shin Youngmin , Jo Taehee , Choi Jaehoon , Kim Junhyung , Jeong Woonhyeok 
Published: September 2024

Background:
There are various opinions on the optimal timing for performing secondary alveolar bone grafting (SABG). This study compared dental health and 3-dimensional outcomes according to the timing of SABG surgery.

Patients and Methods:
A retrospective chart review was performed in patients who underwent SABG between January 1996 and October 2020. Patients were divided into early SABG (6–8 y old) and traditional SABG (9–13 y old) groups. The final dental survival of the lateral incisor and canine teeth, survival of the bone graft, and maxillary growth were analyzed using plain radiographs and computed tomography with a 3-dimensional volumetric analysis tool.

Results:
Thirty-six patients were divided into an early group (15 patients) and a traditional group (21 patients). Five patients had bilateral cleft lip, and 26 patients had unilateral cleft lip and palate; therefore, 36 alveolar clefts were analyzed in this study. Lateral incisor survival was significantly greater in the early group than in the traditional group (60% vs. 23.5%; P<0.05). Compared with that in the traditional group, graft success in the early group was greater (80% vs. 57.1%; P<0.05). Three-dimensional volumetric analysis revealed superior bone graft efficiency in the early group compared with the traditional group (55.2 vs. 38.5%; P<0.05). There was no significant difference in maxillary growth between the 2 groups.

Conclusions:
In our study, superior dental and clinical outcomes were observed in the early SABG group without any long-term complications or maxillary retrusion. Our institution cautiously indicated that SABG could be performed at an age earlier than the existing SABG performed after 9 years old.
Transarterial Radioembolization Can Downstage Intermediate and Advanced Hepatocellular Carcinoma to Liver Transplantation
Authors: Berardi Giammauro , Guglielmo Nicola , Cucchetti Alessandro , Usai Sofia , Colasanti Marco , Meniconi Roberto Luca , Ferretti Stefano , Mariano Germano , Angrisani Marco , Sciuto Rosa , Di Stefano Federica , Ventroni Guido , Riu Pascale , Giannelli Valerio , Pellicelli Adriano , Lionetti Raffaella , D’Offizi Giampiero , Vennarecci Giovanni , Maritti Micaela , Tritapepe Luigi , Cianni Roberto , Ettorre Giuseppe Maria 
Published: September 2024

Background.
Transarterial radioembolization (TARE) is an effective treatment to control tumor growth and improve survival in hepatocellular carcinoma (HCC). The role of TARE in downstaging patients to liver transplantation (LT) is unclear. The aim of this study was to investigate the downstaging efficacy of TARE for intermediate and advanced HCC.

Methods.
Intention-to-treat analysis with multistate modeling was performed. Patients moved through 5 health states: (1) from TARE to listing, (2) from TARE to death without listing, (3) from listing to LT, (4) from listing to death without LT, and (5) from transplant to death. Factors affecting the chance of death after TARE were considered to stratify outcomes.

Results.
Two hundred fourteen patients underwent TARE. Of those, 43.9% had radiological response, 29.9% were listed, and 22.8% were transplanted. The probability of being alive without LT was 40.5% 1 y after TARE and 11.5% at 5 y. The chance of being listed was 9.4% at 1 y and 0.9% at 5 y. The probability of dying after TARE without LT was 38% at 1 y and 73% at 5 y. The overall survival of patients receiving LT was 61% at 5 y after transplant. Tumor beyond up-to-seven criteria, alfafetoprotein >400 ng/mL, and albumin-bilirubin ≥2 were associated with death. Three risk groups were associated with different response, chances of being listed, and receiving LT. Median survival was 3 y for low-risk, 1.9 y for intermediate-risk, and 9 mo for high-risk patients (P < 0.001).

Conclusions.
In intermediate and advanced HCC, TARE allows for a 44% chance of response, 30% downstaging, and 23% probability of permitting LT. Patient’s and tumor’s characteristics allow for risk stratification and predict survival from TARE.
Donor-derived Cell-free DNA Evaluation in Pediatric Heart Transplant Recipients: A Single-center 12-mo Experience
Authors: Sorbini Monica , Aidala Enrico , Carradori Tullia , Vallone Francesco Edoardo , Togliatto Gabriele Maria , Caorsi Cristiana , Mansouri Morteza , Burlo Paola , Vaisitti Tiziana , Amoroso Antonio , Deaglio Silvia , Pace Napoleone Carlo 
Published: September 2024

Background.Endomyocardial biopsy (EMB) is considered the gold-standard method to diagnose rejection after heart transplantation. However, the many disadvantages and potential complications of this test restrict its routine application, particularly in pediatric patients. Donor-derived cell-free DNA (dd-cfDNA), released by the transplanted heart as result of cellular injury, is emerging as a biomarker of tissue damage involved in ischemia/reperfusion injury and posttransplant rejection. In the present study, we systematically evaluated dd-cfDNA levels in pediatric heart transplant patients coming for follow-up visits to our clinic for 12 mo, with the aim of determining whether dd-cfDNA monitoring could be efficiently applied and integrated into the posttransplant management of rejection in pediatric recipients.Methods.Twenty-nine patients were enrolled, and cfDNA was obtained from 158 blood samples collected during posttransplant follow-up. dd-cfDNA% was determined with a droplet-digital polymerase chain reaction assay. EMB scores, donor-specific antibody measurements, and distress marker quantification were correlated with dd-cfDNA, together with echocardiogram information.Results.The percentage of dd-cfDNA increased when EMBs scored positive for rejection (P = 0.0002) and donor-specific antibodies were present (P = 0.0010). N-terminal pro-B-type natriuretic peptide and high-sensitive troponin I elevation were significantly associated with dd-cfDNA release (P = 0.02 andP < 0.0001, respectively), as were reduced isovolumetric relaxation time (P = 0.0031), signs of heart failure (P = 0.0018), and treatment for rejection (P = 0.0017). By determining a positive threshold for rejection at 0.55%, the test had a negative predictive value maximized at 100%.Conclusions.Collectively, results indicate that dd-cfDNA monitoring has a high negative prognostic value, suggesting that in heart transplanted children with dd-cfDNA levels of <0.55% threshold, protocol EMBs may be postponed.
Interpretable high-resolution dimension reduction of spatial transcriptomics data by SpaHDmap
Authors: Tang Junjie , Chen Zihao , Qian Kun , Huang Siyuan , He Yang , Yin Shenyi , He Xinyu , Ye Buqing , Zhuang Yan , Meng Hongxue , Xi Jianzhong Jeff , Xi Ruibin 
Published: September 2024

AbstractSpatial transcriptomics (ST) technologies have revolutionized tissue architecture studies by capturing gene expression with spatial context. However, high-dimensional ST data often have limited spatial resolution and exhibit considerable noise and sparsity, posing significant challenges in deciphering subtle spatial structures and underlying biological activities. Here, we introduce SpaHDmap, an interpretable dimension reduction framework that enhances spatial resolution by integrating ST gene expression with high-resolution histology images. SpaHDmap incorporates non-negative matrix factorization into a multimodal fusion encoder-decoder architecture, enabling the identification of interpretable, high-resolution embeddings. Furthermore, SpaHDmap can simultaneously analyze multiple samples and is compatible with various types of histology images. Extensive evaluations on synthetic and real ST datasets from various technologies and tissue types demonstrate that SpaHDmap can effectively produce highly interpretable, high-resolution embeddings, and detects refined spatial structures. SpaHDmap represents a powerful approach for integrating ST data and histology images, offering deeper insights into complex tissue structures and functions.
Loss of PRICKLE1 in the myometrium leads to reduced fertility, abnormal myometrial architecture, and aberrant extracellular matrix deposition in mice
Authors: Roberts Emily R , Ganeshkumar Sornakala , Gunewardena Sumedha , Chennathukuzhi Vargheese M 
Published: September 2024

AbstractUterine leiomyomas (UL) are the most prevalent benign tumors of the female reproductive tract, originating from the myometrium and affecting over 75% of reproductive-age women. Symptoms of UL include pelvic pain, pressure, dysmenorrhea, menorrhagia, anemia, and reproductive dysfunction. Currently, there is no effective long-term pharmacotherapy for UL, making them the leading cause of hysterectomies in the United States. The lack of treatment options is attributed to the absence of accurate animal models and a limited understanding of UL pathogenesis. Previous research has shown the loss of repressor of element 1 silencing transcription factor/neuron-restrictive silencing factor (REST/NRSF) within the myometrium promotes UL pathogenesis. In addition, deletion ofRestin the mouse myometrium leads to a UL phenotype. PRICKLE1, also known as Rest-interacting LIM-domain Protein (RILP), is required for nuclear localization of REST and Wnt/planar cell polarity (PCP) signaling, making it a critical target for UL studies. In the context of PCP, smooth muscle cells in UL show abnormal organization, aberrant ECM structure, and expression levels, potentially influenced by PRICKLE1 loss. The exact role of PRICKLE1 and Wnt/PCP in UL pathogenesis remains unclear.To explore PRICKLE1’s role in UL, we deletedPrickle1using our myometrial-specific icre. Our findings demonstrate thatPrickle1loss in the myometrium results in a UL phenotype characterized by altered collagen expression, excessive extracellular matrix (ECM) deposition, aberrant smooth muscle cell organization, increasedEsr1andPgrexpression, and dysregulated Wnt/PCP signaling. This novel mouse model serves as a valuable preclinical tool for understanding UL pathogenesis and developing future pharmacotherapies.
Development in the cold renders bird mitochondria more susceptible to heat stress
Authors: Correia Maria , Thoral Elisa , Persson Elin , Chamkha Imen , Elmér Eskil , Nord Andreas 
Published: September 2024

AbstractResearch on birds suggests that extreme weather events during development may have long-lasting consequences on form and function. The underlying cellular mechanisms mediating such phenotypic effects are poorly studied. We raised Japanese quail in warm (30°C) or cold (10°C) temperatures from hatching until adulthood, and then measured mitochondrial metabolism in intact blood cells at representative normothermic body temperature (41°C) and a hyperthermic temperature (45°C) that quail commonly attain when heat stressed. To investigate whether any developmental effects were reversible, half of the cold- and warm-acclimated birds were assigned to a common garden (20°C) 3 weeks before the measurements. Across groups, hyperthermia was associated with increased proton leak, but decreases in both phosphorylating respiration (where ATP is produced) and working capacity of the mitochondria. Cold-acclimated birds were more strongly affected by heat stress: the increase in proton leak was 1.6-fold higher, and the decrease in phosphorylating capacity during endogenous respiration was 1.7-fold greater, compared to warm-acclimated birds. These differences did not remain in the common-garden birds. Our study suggests that developmental cold acclimation is traded off against heat tolerance at the level of cellular metabolism, with implications for our understanding of avian responses to climate change.
Contraceptive Outcomes of the Natural Cycles Birth Control App: A Study of Canadian Women
Authors: Benhar Eleonora , van Lamsweerde Agathe , Krauss Kerry , Berglund Scherwitzl Elina , Scherwitzl Raoul 
Published: September 2024

AbstractObjectiveThis study aimed to investigate the key demographics and evaluate the real-world contraceptive failure and continuation rates of the Natural Cycles app in a cohort of women from Canada.MethodsThis was a real-world, prospective cohort study. Demographics were assessed via in-app questionnaires. Contraceptive failure rates in typical and perfect use were calculated using the 13-cycle cumulative pregnancy probability (Kaplan-Meier survival analysis) and the one-year Pearl Index (PI). One-year continuation rates were estimated through survival analysis.ResultsThe study included 8 ‘798 women who contributed an average of 9.2 months of data, amounting to a total of 7’ 063 woman-years of exposure. The average user was 27.3 years old, had a body mass index of 24.6, and reported being in a stable relationship. With typical use, the app demonstrated a 13-cycle cumulative pregnancy probability of 4.8 [95% CI: 4.3, 5.4] and a Pearl Index of 4.3 [95% CI: 3.9, 4.8]. Under perfect use, the contraceptive failure rate was 2.3 [95% CI: 0.7, 3.9] for life table analysis and 1.7 [95% CI: 0.5, 2.8] for the 1-year PI. The contraceptive method’s continuation rate after one year was 62.4%.ConclusionsThe data presented in this study offer valuable insights into the cohort of women using the Natural Cycles app in Canada and provide country-specific effectiveness estimates. The app’s contraceptive effectiveness aligns with previously published data on Natural Cycles.
Tucaresol: A Clinical Stage Oral Candidate Drug With Two Distinct Antiviral Mechanisms
Authors: Penney Christopher L. , Zacharie Boulos , Duceppe Jean-Simon 
Published: September 2024

AbstractGlobally, approximately 39 million people are living with Human Immunodeficiency Virus, HIV, arising from approximately 86 million infections since this epidemic began in 1981. However, the number of HIV infections is unevenly distributed with two thirds of global infections confined to Sub-Saharan Africa. Due to viral drug resistance, the most effective treatment requires a triple drug combination thereby adding to the complexity and cost of therapy. As such, many people living with HIV or at risk of infection do not have access to prevention or treatment of this potentially fatal disease. There is no cure for HIV [1]. Tucaresol is an orally active clinical stage drug which functions as a host targeted antiviral agent by protection or reconstitution of CD4+ T helper immune cells. We report herein that Tucaresol also displays in-vitro activity against HIV in infected human peripheral blood mononuclear cells. Although this in-vitro antiviral activity is not potent, the excellent safety profile and bioavailability of Tucaresol, along with its low Molecular Weight, support attainment of relevant drug concentrations in man to achieve significant in-vivo activity. This is demonstrated by previously reported stabilization of viremia in a prior proof of concept phase 1b/2a HIV clinical trial [2]. It is possible that the significant in-vivo activity of Tucaresol arises from synergy between co-stimulation of CD4+ T helper cells and the direct activity against virally infected cells. A pan in-vitro viral screen of Tucaresol further revealed a weak, direct antiviral activity against human herpes virus 6B, human papillomavirus 11, measles virus and hepatitis B virus.
p53 Regulates Nuclear Architecture to Reduce Carcinogen Sensitivity and Mutagenic Potential
Authors: King Devin A. , McCoy Dakota E. , Perdyan Adrian , Mieczkowski Jakub , Douki Thierry , Dionne Jennifer A. , Herrera Rafael E. , Morrison Ashby J. 
Published: September 2024

AbstractThe p53 tumor suppressor is an indispensable regulator of DNA damage responses that accelerates carcinogenesis when mutated. In this report, we uncover a new mechanism by which p53 maintains genomic integrity in the absence of canonical DNA damage response activation. Specifically, loss of p53 dramatically alters chromatin structure at the nuclear periphery, allowing increased transmission of an environmental carcinogen, ultraviolet (UV) radiation, into the nucleus. Genome-wide mapping of UV-induced DNA lesions in p53-deficient primary cells reveals elevated lesion abundance in regions corresponding to locations of high mutation burden in malignant melanomas. These findings uncover a novel role of p53 in the suppression of mutations that contribute to cancer and highlight the critical influence of nuclear architecture in regulating sensitivity to carcinogens.One-Sentence SummaryThe p53 tumor suppressor reduces carcinogen sensitivity and mutagenic potential by maintaining nuclear architecture.
Viral transcript and tumor immune microenvironment-based transcriptomic profiling of HPV-associated head and neck squamous cell carcinoma identifies subtypes associated with prognosis
Authors: Nikitina Anastasia , Kiriy Daria , Tyshevich Andrey , Tychinin Dmitry , Antysheva Zoia , Sobol Anastasia , Kushnarev Vladimir , Shin Nara , Brown Jessica H. , Lewis James , Kuhs Krystle A. Lang , Ferris Robert , Wirth Lori , Kotlov Nikita , Faden Daniel L. 
Published: September 2024

AbstractHuman papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HPV-positive HNSCC) has distinct biological characteristics from HPV-negative HNSCC. Using an AI-based analytical platform on meta cohorts, we profiled expression patterns of viral transcripts and HPV viral genome integration, and classified the tumor microenvironment (TME). Unsupervised clustering analysis revealed 5 distinct and novel TME subtypes across patients (immune-enriched, highly immune and B-cell enriched, fibrotic, immune-desert, and immune-enriched luminal). These TME subtypes were highly correlated with patient prognosis. In order to understand specific factors associated with prognosis, we used unsupervised clustering of a HPV-positive HNSCC cohort from The Cancer Genome Atlas (TCGA) (n = 53) based on HPV transcript expression, and identified 4 HPV-related subtypes (E2/E5, E6/E7, E1/E4 and L1/L2). Utilizing both viral transcript and TME subtypes, we found that the E2/E5 HPV subtype was associated with an immune-enriched TME and had a higher overall survival compared to other subtypes. The E2/E5 subtype was also enriched for samples without HPV-genome integration, suggesting that episomal HPV status and E2/E5 expression pattern may be associated with an inflamed microenvironment and improved prognosis. In contrast, E6/E7 subtype samples were associated with the fibrotic and immune-desert TME subtypes, with lower values of T-cell and B-cell gene expression signatures and lower overall survival. Both E1/E4 and L1/L2 subtypes were associated with the immune-enriched luminal subtype. Our results suggest that HPV- transcript expression patterns may drive modulation of the TME and thereby impact prognosis.