bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does controlled, gradually increased venous pressure exposure (dangling) of the lower extremity after free flap reconstructions reduce partial flap loss? A multicenter randomized controlled trial
Authors: Krijgh David D. , List Emile B. , Qiu Shan S. , Schols Rutger M. , Mureau Marc A.M. , Luijsterburg Antonius J.M. , Tempelman T.M.T. , van der Beek E.S.J. , Coert J. Henk , Teunis Teun , Maarse Wiesje ,   Dangle Research Group (Laurentien .S.E. van Egdom M.D Ph.D.; Arda. Goceroglu M.D., Ph.D; Nadine.S. Hillberg, M.D., Ph.D; Jop. Beugels, M.D., Ph.D)
Published: December 2024

Introduction:
Controlled, gradually increased venous pressure exposure of lower extremity free flaps (dangling) is common, based on the assumption that this reduces (partial) flap loss. Dangling protocols potentially increase length of hospital stay and resource utilization. We investigated whether: (1) the proportion of partial flap loss 6 weeks after lower extremity free flap reconstruction is non-inferior after uncontrolled exposure compared to gradually increased venous pressure exposure; (2) there is a difference in length of hospital stay and major or minor adverse events 3 months after surgery.

Materials and Methods:
For this multicenter randomized controlled trial patients who underwent lower extremity free flap reconstruction were included. Seven days after surgery 39 were randomized to dangling and 36 mobilized without limitations. Partial flap loss was assessed 6 weeks after surgery (primary outcome), length of stay, and major and minor adverse events 3 months after surgery. An absolute increase of 12% partial flap loss was considered inferior.

Results:
Uncontrolled exposure was non-inferior to controlled, gradually increased venous pressure exposure (absolute risk difference: 2.4%, 95% CI -10%-15%, partial flap loss dangling: 5.1% (n=2) vs. non-dangling: 2.8% (n=1)). There was no difference in length of stay and major or minor complications.

Conclusion:
Seven days after surgery, dangling the lower extremity after free flap reconstruction seems unnecessary. Surgeons and patients can consider forgoing a formal dangling protocol at that time. Future research is warranted to assess whether forgoing dangling is also safe earlier after free tissue transfer possibly reducing length of hospital stay and resource utilization.
Outcomes of all-dorsal augmented intercarpal ligament reconstruction (ADAIR)
Authors: Colwell Jennifer L. , Florczynski Matthew M. , Riggs Jeanne M. , Kim Hyungjin M. , Burns Patricia B. , Chung Kevin C. 
Published: December 2024

Background:
Scapholunate (SL) and lunotriquetral (LT) ligament injuries are frequently undiagnosed and can lead to progressive loss of wrist function and chronic pain. Many surgical reconstruction options exist, but outcomes are suboptimal and no superior approach has been established.

Methods:
Consecutive candidates for SL and/or LT ligament reconstruction utilizing an all-dorsal augmented intercarpal ligament reconstruction (ADAIR) were evaluated in this prospective case series. The Michigan Hand Questionnaire (MHQ), Patient-Rated Wrist Evaluation (PRWE), range of motion, and grip and pinch strength were administered preoperatively and at postoperative visits up to 12 months.

Results:
Twenty-two patients (24 wrists) were included in the study, with 17 wrists followed to 6 months and 15 wrists to 12 months postoperatively. In the operated extremity, overall MHQ scores improved over 12 months by a mean of 17.2 points (p < 0.001). All MHQ domain scores except aesthetic and work domains showed significant improvement. Overall PRWE scores improved by 24.1 points by 12 months (p < 0.001). At 12 months, all clinical outcomes, including grip and pinch strength, wrist range of motion, and radiographic measurements were improved or similar to baseline.

Conclusions:
ADAIR demonstrated encouraging short-term patient-reported and functional outcomes, comparable to other intercarpal reconstructions despite its relative technical simplicity. ADAIR is a promising technique for improving outcomes in these challenging surgical cases.
Increasing the Accessibility and Relevance of Implementation Science for Front-Line Implementers
Authors: Golub Sarit A. , Wolfer Carly , Chastain Cody A. 
Published: December 2024

Background:
Implementation science has been heralded as a critical strategy for ending the HIV epidemic, and the United States has made a tremendous financial investment in implementation research. However, several dynamics in its development and organization may alienate front-line implementers and recapitulate some of the same missteps that have stymied past translational work.

Setting:
Increasing the accessibility and relevance of HIV implementation science for front-line implementers (eg, health department and health systems directors, clinic administrators, program managers, clinicians, and other providers) is critical.

Methods:
We review current challenges to the meaningful inclusion of front-line implementers in implementation science research, and consider specific changes to language, frameworks, and methods that would maximize the accessibility and relevance of the field.

Results:
Our analysis suggests the need for greater attention to implementation strategies most relevant to front-line implementers, that is, those focused on intervention recipients. We propose a novel, multilayer framework for conceptualizing the strategies necessary to achieve HIV implementation outcomes by organizations, providers, and recipients. There is a compelling rationale to adopt incentive structures that prioritize research questions most important for practice.

Conclusions:
Maximizing the impact of implementation science on ending the HIV epidemic goals requires (1) expanding the focus of implementation science to include more recipient-focused implementation strategies, (2) developing and applying frameworks that better reflect the experience and needs of front-line implementers, (3) using language most relevant and applicable to practice, and (4) prioritizing actionable research questions that directly address the needs and concerns of those doing implementation work.
Feasibility of Periauricular Incision for Parotidectomy: A Retrospective Study
Authors: Köroğlu Erdem 
Published: December 2024

Backgrounds:
Various incisions are used in parotid surgery, yet they often result in visible scarring on the neck and potential deformities. This study aimed to assess the efficacy and feasibility of utilizing a periauricular approach for excising parotid tumors irrespective of their location and size.

Methods:
This retrospective study involved 46 consecutive patients with parotid lesions, who underwent minimally invasive excision through a periauricular incision performed by a single surgeon between January 2022 and January 2024. Basic demographic data were recorded. Parameters such as the need for incision extension, total volume of drainage, length of hospital stay, postoperative complications, and final pathological diagnosis were also documented.

Results:
The main trunk of the facial nerve was successfully identified in all patients, and the tumors were excised without requiring incision extension. Warthin tumor was the most common pathology (n=20, 43%). Three patients (6.5%) had malignant tumors. The inferior portion of the superficial lobe was the most frequent tumor location (n=18, 39%), with 11% of patients having deep lobe parotid tumors. Median operation time was 114 min (range, 90–170), tumor size was 2.8 cm (range, 1–6.5 cm), and drainage volume was 45 mL (range, 10–80). Postoperative complications occurred in 7 patients, with sialocele formation being the most common (n=5, 11%). No serious complications like permanent facial paralysis or skin necrosis were observed.

Conclusion:
The periauricular approach is feasible for parotid tumors across all levels of the parotid gland. Its cosmetic advantage lies in the smaller scar size that does not extend into the neck.
USP33 promotes caerulein-induced apoptotic, oxidative and inflammatory injuries in acute pancreatitis by deubiquitinating TRAF3
Authors: Guo Jian , Qu Huiheng , Cui Peng , Xue Yu 
Published: December 2024

Abstract

Background: Tumor necrosis factor receptor associated factor 3 (TRAF3) and deubiquitinating enzyme ubiquitin-specific protease 33 (USP33) have been identified to play important roles in inflammatory diseases, including acute pancreatitis (AP). Here, we aimed to explore whether USP33 affected AP progression by affecting TRAF3 expression through deubiquitination.

Methods: Caerulein-treated HPDE6-C7 cells were used to mimic AP conditions in vitro. Levels of mRNAs and proteins were examined by qRT-PCR and Western blot. Cell proliferation and apoptosis were evaluated using CCK-8 assay, EdU assay and flow cytometry. Cell oxidative stress was assessed by detecting the production of superoxide dismutase and malonaldehyde. ELISA analysis detected IL-6 and TNF-α levels. Macrophage M1 polarization was evaluated by flow cytometry. Cellular ubiquitination analyzed the ubiquitination effect on TRAF3. Protein interaction between USP33 and TRAF3 was identified by immunofluorescence staining.

Results: Caerulein dose-dependently induced apoptosis, oxidative stress, and inflammatory response in HPDE6-C7 cells and promoted macrophage M1 polarization to enhance inflammation (P < 0.05). TRAF3 was highly expressed in AP patients (3.5±1.10 vs. 1.0 ±0.74, P < 0.05) and caerulein-induced HPDE6-C7 cells (3.3 ±0.34 vs. 1.0 ±0.10, P < 0.05). Knockdown of TRAF3 protected HPDE6-C7 cells from caerulein-induced apoptotic, oxidative and inflammatory injuries. Mechanistically, USP33 interacted with TRAF3 and induced TRAF3 deubiquitination to up-regulate its expression (P < 0.05). Further analyses showed that USP33 knockdown reversed caerulein-induced apoptosis, oxidative stress and inflammation in HPDE6-C7 cells by TRAF3 (P < 0.05). Moreover, USP33-TRAF3 activated the NF-κB pathway (P < 0.05).

Conclusion: USP33 promoted caerulein-induced apoptosis, oxidative stress and inflammation in pancreatic ductal cells by deubiquitinating TRAF3, indicating a novel insight into the pathogenesis of AP.
Low dose oral ketamine treatment on post-traumatic stress disorder (PTSD) (OKTOP): An open-label pilot study
Authors: Quigley Bonnie L. , Can Adem T. , Dutton Megan , Gallay Cyrana C. , Forsyth Grace , Jones Monique , Randall Fiona , Wilson Trish , Lagopoulos Jim , Hermens Daniel F. 
Published: December 2024

AbstractKetamine is being actively investigated as a rapid-acting treatment for many conditions with a stress-related psychopathology, including post-traumatic stress disorder (PTSD). The majority of studies regarding ketamine treatment for PTSD to date (including open-label and randomised control trials) have focused on intravenous (IV) ketamine administration. This administration route has limitations that can be overcome with oral ketamine. As such, this study undertook the first open-label low dose Oral Ketamine Trial on PTSD (OKTOP) to determine the safety and feasibility of sub-anaesthetic ketamine for PTSD symptom reduction. Participants with PTSD (n = 22 adults, aged 22-77 years, 55% female, 82% with comorbid depression) followed a weekly treatment course of low dose oral ketamine (titrated from 0.5 mg/kg to a maximum of 3.0 mg/kg) for six weeks. The primary outcome measure was the PTSD Checklist (PCL-5), with secondary measures including scales for depression, anxiety, stress, suicidality, sleep, and wellbeing. Mean PCL-5 scores were significantly reduced from a pre-ketamine baseline score of 40 to a post-ketamine score of 17 and remained at a reduced score (21) at follow-up, 1-month post-treatment. This reduction resulted in a response rate (defined as a ≥50% reduction in PCL-5 score from baseline) of 73% post-ketamine and 59% at follow-up. This response rate is comparable with IV ketamine trials for PTSD and suggests oral ketamine administration is a feasible and tolerable treatment for PTSD.
A Phase II/III, Randomized, double-blind, placebo-controlled trial to evaluate Immunogenicity and Safety of the Gam-COVID-Vac combined vector vaccine in the prophylactic Treatment for SARS-CoV-2 infection in the United Arab Emirates
Authors: Al Hammadi Ahmed AK. , Alzaabi Amna H. , Choker Haneen B. , Ibrahim Ahmed A. , Ishaq Asma Bin , Mahboub Ahmed E. , Al Dhaheri Reem S. , Alzaabi Mohamed N. , Collyns Timothy A. , ElGhazali Gehad , Weber Stefan , al-Ramadi Basel K. 
Published: December 2024

AbstractBackgroundDifferent platforms were used to develop vaccines against SARS-CoV-2 which were instrumental in bringing an end to the pandemic. Nevertheless, long term efficacy and safety profiles of the various vaccine types is still being investigated. The current trial aimed to assess the safety and immunogenicity of the Gam-COVID-Vac combined vector vaccine against SARS-CoV-2-induced coronavirus infection up to 6 months post vaccination.MethodsIn this randomized, double-blind, placebo-controlled trial, study participants ≥18 years of age with no prior SARS-COV-2 infection or vaccination were randomized (3:1) to receive the heterologous recombinant human adenovirus-vectored vaccines serotypes 26 and 5 or placebo. Immunogenicity was determined based on quantitative IgG antibodies (Abs) to viral S and N proteins, virus-neutralizing Abs (VNA), seroconversion rates, and S protein-specific CD4 and CD8 T cell responses.ResultsA total of 990 participants were randomized to the vaccine (n=74) and placebo (n=246) groups. Overall incidence of Adverse events (AEs) was 1844 (81.5%) in the vaccine and 501 in placebo (82.1%) groups, the majority being in the mild/moderate categories. Two doses of vaccine induced VNA in 100% of participants on Day 42, with geometric mean ratio (GMR) reaching maximum at 120 days with average 24.14 (p<0.001). Vaccine group showed a very significant GMR for quantitative IgG to S protein. Difference in seroconversion rates was also significant with 90.0%, 83.7% and 78.9% on days 42, 120 and 180 (p<0.001 at all three points). A significant rise in the median of S protein-specific CD4+and CD8+T-lymphocytes with a robust IFN-γ response was evident after 28 days compared to baseline. Long-term follow-up demonstrated persistent and significant CD8+T cell and IFN-γ responses at 120 days (p=0.049 and 0.039, respectively) compared to placebo group.ConclusionGam-COVID-Vac vaccine showed a good safety profile and induced strong and durable humoral and cellular immune responses. The viral-specific CD8+T cell response appears to be more durable following vaccination than CD4+T cell counterpart. Importantly, there was no evidence of any severe or persistent AEs in vaccinees suggestive of long COVID syndrome, emphasizing the safety of this heterologous prime-boost vaccine.
Assessing Bias in Gene Expression Omnibus (GEO) Datasets
Authors: Gondal Mahnoor N. 
Published: December 2024

AbstractThe Gene Expression Omnibus (GEO) is a widely used repository for gene expression data, but its datasets may be subject to biases in terms of diversity, equity, and inclusion. This study aims to assess DEI-related biases in GEO datasets specifically focusing on gender and ethnicity representation. We curated a subset of GEO datasets by applying filters for organism type, sample size, and DEI-related metadata (gender and ethnicity). Following rigorous data extraction and cleaning, we analyzed 211 datasets, evaluating gender balance and ethnicity/race distribution using quantitative metrics. For gender representation, we calculated a gender ratio for each dataset, with a ratio closer to 1 indicating balanced representation. Ethnicity/race representation was assessed using Chi-square goodness-of-fit tests to identify disparities in ethnic distribution. We ranked datasets based on these DEI criteria to identify those with the highest and lowest bias. Our findings revealed that while many datasets displayed balanced gender ratios, significant bias in ethnicity representation was observed, with a predominance of White and African American participants. Additionally, we observed some variation in DEI metrics for datasets published before and after 2015, suggesting a shift in gender recruitment practices. These results highlight the need for more inclusive data collection and reporting in genomic research. We emphasize the importance of incorporating DEI criteria into data curation and encourage future efforts to standardize DEI data reporting across repositories to mitigate bias and improve the generalizability of genomic research.
Dona Flor and her two husbands: Discovery of novel HDAC6/AKT2 inhibitors for myeloid cancer treatment
Authors: Waitman Karoline B. , Martin Holli-Joi , Carlos Jorge A. E. G. , Braga Rodolpho C. , Souza Vinícius A. M. , Melo-Filho Cleber C. , Hilscher Sebastian , Toledo Mônica F. Z. J. , Tavares Maurício T. , Costa-Lotufo Letícia V. , Machado-Neto João A. , Schutkowski Mike , Sippl Wolfgang , Kronenberger Thales , Alves Vinicius M. , Parise-Filho Roberto , Muratov Eugene N. 
Published: December 2024

AbstractHematological cancer treatment with hybrid kinase/HDAC inhibitors is a novel strategy to overcome the challenge of acquired resistance to drugs. We collected IC50datasets from the ChEMBL database for 13 cancer cell lines (72 h cytotoxicity, measured by MTT), known inhibitors for 38 kinases, and 10 HDACs isoforms, that we identified by target fishing and literature review. The data was subjected to rigorous biological and chemical curation leaving the final datasets ranging from 76 to 8173 compounds depending on the target. We generated Random Forest classification models, whereby 14 showed greater than 80% predictability after 5-fold external cross-validation. We screened 30 hybrid kinase/HDAC inhibitor analogs through each of these models. Fragment-contribution maps were constructed to aid the understanding of SARs and the optimization of these compounds as selective kinase/HDAC inhibitors for cancer treatment. Among the predicted compounds, 9 representative hybrids were synthesized and subjected to biological evaluation to validate the models. We observed high hit rates after biological testing for the following models: K562 (62.5%), MV4-11 (75.0%), MM1S (100%), NB-4 (62.5%), U937 (75.0), and HDAC6 (86.0%). This aided the identification of6band6kas potent anticancer inhibitors with IC50of 0.2-0.8 µM in three cancer cell lines, linked to HDAC6 inhibition below 2 nM, and blockade of AKT2 phosphorylation at 2 μM, validating the ability of our models to predict novel drug candidates.Graphical AbstractHighlightsNovel kinase/HDAC inhibitors for cancer treatment were found using machine learning61 QSAR models for hematological cancers and its targets were built and validatedK562, MV4-11, MM1S, NB-4, U937, and HDAC6 models had hit rates above 62.5% in tests6band6kpresented potent IC50of 0.2-0.8 µM in three cancer cell lines6band6kinhibited HDAC6 below 2 nM, and blockade of AKT2 phosphorylation at 2 μM
Cannabidiol promotes apoptosis and downregulation of oncogenic factors
Authors: Greenwood Ashley , Yamamoto Tomomi M. , Joshi Molishree , Hutchison Kent , Bitler Benjamin G. 
Published: December 2024

ABSTRACTPatients with high-grade serous carcinoma of tubo-ovarian origin (HGSC) often experience significant side effects related to their disease and treatments, such as pain, discomfort, nausea, and vomiting. Over the last two decades, the use of cannabinoids (CBD) to manage pain and anxiety has become more mainstream. However, there is limited data on how CBD interacts with HGSC tumor cells or whether CBD impacts the effect of chemotherapy.Prior preclinical data has suggested the antitumor benefits of cannabinoids; however, the mechanism and data in ovarian cancer are limited. The objectives of this proposed research are to define the endocannabinoid system milieu in ovarian cancer, determine if CBD influences the growth of ovarian cancer cells, measure the cell viability when cannabinoids such as CBD are combined with standard-of-care therapies, and identify potential molecular pathways in which cannabinoids have a therapeutic effect. We conducted publicly available database searches, in vitro proliferation and apoptotic assays, functional protein signaling via reverse phase protein array analysis of CBD-treated cells using 2D cultured cells, and immunohistological analysis of ex vivo cultured patient-derived tumor slices treated with CBD.Our data suggests that CBD is unlikely to affect the growth of cancer cells at physiologic doses but promotes apoptosis and can have growth inhibitory effects at higher concentrations. The inhibitory effects seen at high dose concentrations are likely from the upregulation of apoptotic pathways and inhibition of oncogenic pathways. Overall, physiologic CBD levels have minimal impact on cancer cell growth or chemotherapy efficacy.
Predicting Tissue of Origin from Bulk Tumor Gene Expression using a Pre-trained Transformer Model
Authors: Mellors Ted , Spitmann Mehran 
Published: December 2024

AbstractIdentifying the tissue of origin for cancers is essential for enhancing diagnostic precision, selecting effective treatments, and guiding clinical decision-making. In this study, we developed a predictive model to classify the tissue of origin across various cancer types. Using a dataset with 10,300 samples from 32 unique tissue types, the model achieved an overall accuracy of 88% in distinguishing among all 32 classes, with an average accuracy of 99.2% within each class. When tested on metastatic skin tumors, it reached an accuracy of 87%, underscoring its potential in addressing challenging metastatic cases. These results demonstrate the model’s reliability in oncology applications, offering a promising tool for improving diagnostic accuracy and supporting personalized cancer treatment strategies.
Microvascular pulsatility of the ageing brain and confounding effects of anaesthesia
Authors: Skøtt Mia Viuf , Melnikova Elizaveta , Gutiérrez Eugenio , Matchkov Vladimir , Østergaard Leif , Postnov Dmitry D 
Published: December 2024

AbstractMicrovascular pulsatility in the brain is crucial for sustaining the delicate balance between the brain’s metabolic demands and blood supply, as it affects nutrient exchange, waste removal and blood-brain barrier permeability. Abnormal pulsatility, associated with ageing or vascular risk factors, may impair the clearance of metabolic waste or contribute to conditions such as cerebral small vessel disease, ultimately leading to dementia and increasing the risk of stroke. In the present study, we introduce a new approach for robust full-field characterization of microvascular pulsatility and apply it to study cerebral perfusion and pulsatility across nearly the entire lifespan of awake and anaesthetized C57BL/6 mice. Our findings in awake animals reveal remarkably stable perfusion and pulsatility from 18 to 81 weeks, with pulsatility starting to change only in the final weeks of observation. In contrast, measurements taken under anaesthesia display a range of age-dependent and age-independent changes. We show that isoflurane affects the perfusion in an age-dependent manner, and both isoflurane and ketamine-xylazine, despite their distinct mechanisms, double the perfusion pulsatility and affect vascular diameter pulsatility in a complex manner, highlighting a previously overlooked detrimental effect of anaesthesia on assessing brain function.