bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgery With or Without Radiotherapy Versus Radiotherapy Alone for Malignant Spinal Cord Compression
Authors: Haro-Perez Patricio , Pinzon-Leal Daniela , Del Pozo-Acosta Prisca , Cruz-Bravo Michael , Ortiz-Ordonez Andrea 
Published: October 2024

Study Design:
A systematic review and meta-analysis

Objective:
To conduct a meta-analysis of studies that compared surgery with or without radiotherapy to radiotherapy alone for patients with malignant spinal cord compression, and a subgroup analysis of patients stratified by hematologic and solid malignancies.

Summary of Background Data:
Two previous meta-analyses showed that surgery with or without radiotherapy was better than radiotherapy alone in patients with malignant spinal cord compression. Nevertheless, there was no stratification by tumor type, leading to uncertainty regarding best approach for patients with hematologic malignancies.

Methods:
We searched PubMed, Scopus, and Web of Science, for studies comparing surgery with or without radiotherapy to radiotherapy alone in patients with malignant spinal cord compression. The primary outcomes were improvement in ambulatory status and survival at 12 months. For neurological outcomes, we included studies involving both locally advanced primary malignancies of the spine and metastatic tumors. We restricted our analysis to studies on metastases for survival outcomes.

Results:
We included 2536 patients from 18 studies. Surgery was performed in 890 (35%) patients. The pooled analysis of all studies revealed that improvement in ambulatory status (OR 2.65; 95% CI 1.60-4.39) and survival at 12 months (OR 1.66; 95% CI 1.10-2.52) were significantly higher in patients who underwent surgery with or without radiotherapy. Improvement in ambulatory status (OR 1.92; 95% CI 1.19-3.09) and survival at 12 months (OR 4.24; 95% CI 2.35-7.66) were significantly higher in patients with hematologic malignancies in the surgical arm. The primary outcomes were not significantly different between patients with solid malignancies.

Conclusion:
Surgical intervention demonstrates superior neurological outcomes and increased survival compared with radiotherapy alone. Subgroup analysis revealed that patients with hematologic malignancies on surgery group experienced superior primary outcomes; however, high risk of bias of the included studies preclude definitive changes in standard care based on this data. These findings underscore the need for further research regarding the efficacy of surgical versus radiotherapeutic approaches for specific tumor types.

Level of Evidence:
2
Use of Albumin In Situ Hybridization to Diagnose Cutaneous Metastatic Hepatocellular Carcinoma With Poorly Differentiated Features: A Case Report and Review of the Literature
Authors: Gauger Andrew J. , Li Aofei , Fritz Mike , Katona Terrence M. , Alomari Ahmed K. 
Published: October 2024

Abstract:
Hepatocellular carcinoma (HCC) rarely metastasizes to the skin. When it occurs, it is often poorly differentiated making the diagnosis challenging. There exists a male predominance, and clinical presentation usually includes papules or nodules resembling pyogenic granulomas or dermal deposits. Histopathology shows malignant dermal cells. Hepatoid features including nests or cords of cells arranged in a trabecular or pseudoglandular pattern, sinusoidal formation, or the presence of bile exist in less than 50% of cases. Limitations exist with immunohistochemical staining, particularly in poorly differentiated neoplasms. Albumin in situ hybridization is more sensitive for detecting poorly differentiated HCC. Immunostaining in conjugation with albumin in situ hybridization enhances the detection of metastatic hepatocellular carcinoma. We report the case of a 74-year-old man with a history of HCC and a stable lung metastasis who presented with painful, growing bumps on his nose for 2 months. Examination revealed multiple, pink to white, shiny dermal-based papules with telangiectasias involving the right nasal tip and naris. Alpha-fetoprotein level was markedly elevated. Computed tomography showed expanding right lower lobe lung nodules. Histopathology of the cutaneous biopsy revealed features of a poorly differentiated basaloid carcinoma. Immunohistochemical staining was diffusely positive for glypican-3, focally positive for arginase-1, and negative for hepatocyte paraffin 1. Albumin in situ hybridization was diffusely positive, clinching the diagnosis of HCC. Metastatic HCC is a rare encounter for dermatopathologists. We aim to increase awareness of its occurrence in patients with advanced HCC and highlight the importance of clinical correlation when faced with poorly differentiated or unusual-looking basaloid neoplasms.
Different degrees of summed difference perfusion score in women: influence on the prognostic variables associated with cardiac events
Authors: Romero-Farina Guillermo , Aguadé-Bruix Santiago , Ferreira-González Ignacio 
Published: October 2024

Objective
Evaluating the predictive models (PM) for a major adverse cardiac event (MACE) only in women with abnormal summed difference score (SDS ≥ 1), borderline myocardial ischemia (borderline-MIsch: SDS = 1), MIsch (SDS ≥ 2), mild-MIsch (SDS = 2–4), and moderate–severe MIsch (ms-MIsch: SDS ≥ 5).

Methods
Between January 2000 and January 2018, of 25 943 consecutive patients who underwent gated single-photon emission computed tomography myocardial perfusion imaging (gSPECT-MPI) for coronary risk stratification; 717 women (age 68.37 ± 3.4 years) with an abnormal SDS ≥ 1 were included. During the follow-up (mean 4 ± 2.9 years) post-gSPECT-MPI, MACE (unstable angina, nonfatal myocardial infarction, coronary revascularization, cardiac death) was assessed.

Results
In the global women cohort with abnormal SDS (n = 717), the PM was angina [hazard ratio (HR): 1.65, P = 0.016], diabetes (HR: 1.72, P = 0.004), beta-blockers (HR: 1.61, P = 0.009), pharmacological stress (HR: 1.74, P = 0.007), ↓ segment (ST) mm ≥ 1 (HR: 1.54, P = 0.039), and moderate-to-severe abnormal summed stress score (ms-SSS) (HR: 2.92, P = 0.001). In borderline-MIsch group (n = 208), the PM was previous myocardial infarction (HR: 3.8, P = 0.001), nitrates (HR: 2.13, P = 0.047), pharmacological stress (HR: 4.81, P < 0.001), and ↓ST mm ≥ 1 (HR: 3.07, P = 0.014). In MIsch group (n = 509), the PM model was ms-SSS (HR: 2.25, P = 0.001), diabetes (HR: 1.73, P = 0.011), angina (HR: 1.68, P = 0.029), beta-blockers (HR: 1.59, P = 0.026), and ms-MIsch (HR: 1.62, P = 0.044). In mild-MIsch group (n = 399), the PM was ms-SSS (HR: 2.55, P = 0.003), diabetes (HR: 2.17, P = 0.004), angina (HR: 1.89, P = 0.037), and beta-blockers (HR: 2.01, P = 0.011). In ms-MIsch group (n = 110), the predictive variable for MACE was ms-SSS (HR: 2.27, P = 0.016). The ms-SSS significantly increases the prognostic value of the ms-MIsch (P = 0.001).

Conclusion
Women with different degrees of abnormal SDS have different PMs of MACE. The ms-SSS stands out as the most significant predictive variable.
Another Tool for the Sexual Health Toolkit: US Health Care Provider Knowledge and Attitudes About Doxycycline Postexposure Prophylaxis to Prevent Bacterial Sexually Transmitted Infections Among Men Who Have Sex With Men
Authors: Perkins Rodney , Beima-Sofie Kristin , Christopoulos Katerina , Cohen Stephanie E. , Dright Aurnell , Dombrowski Julia C. , Gougougui Ashley , Kohler Pamela , Luetkemeyer Anne F. , Pintye Jillian , Celum Connie 
Published: October 2024

Background
Doxycycline post-exposure prophylaxis (doxy-PEP) reduces chlamydia, gonorrhea, and syphilis infections among men who have sex with men (MSM) and transwomen (TW). Perspectives of health care providers (HCPs) regarding doxy-PEP can inform implementation efforts.

Methods
From August 2022 to January 2023, HCPs were recruited from 13 cities with high sexually transmitted infection (STI) rates for semi-structured, in-depth interviews about their awareness of and attitudes toward doxy-PEP for STI prevention. Health care providers were purposively sampled to include people with experience prescribing PrEP and provision of care to MSM. Interviews were conducted virtually via Zoom. Transcripts and debrief reports were analyzed using a directed content analysis approach to explore knowledge, attitudes, and beliefs about doxy-PEP.

Results
Among 30 HCPs, almost half (47%) were between 31–40 years of age, 53% identified as male, and 47% reported their sexual orientation as gay or queer. Half (53%) of participants practiced in the South, 43% had >100 MSM in their clinic panel, and 17% had previously prescribed doxy-PEP. We identified four overarching themes: 1) HCPs expressed positive attitudes toward doxy-PEP; 2) antimicrobial resistance concerns limit enthusiasm for some HCPs; 3) additional data about the long-term safety of doxy-PEP would improve their confidence; and 4) development of guidelines would facilitate the prescription of doxy-PEP, including eligibility, dosing instructions, and treatment management.

Conclusion
HCPs were motivated to prescribe doxy-PEP with almost 20% already having prescribed it. Guidelines and data about long-term safety, especially antimicrobial resistance, would facilitate introduction of doxy-PEP into clinical practice.
SOX17 Expression in Mesotheliomas and Benign Mesothelial Proliferations: Implications for Differential Diagnosis With Gynecologic Carcinomas
Authors: Laokulrath Natthawadee , Hung Yin P. , Watkins Jaclyn C. , Oliva Esther , Devins Kyle M. 
Published: October 2024

SOX17 has recently emerged as a novel immunohistochemical marker for cancers of endometrial and ovarian origin with improved specificity compared with the widely used Mullerian marker PAX8. However, evaluation of SOX17 in benign and malignant peritoneal mesothelial proliferations remains limited, and these may mimic gynecologic carcinomas, particularly on small biopsies. We evaluated SOX17 and PAX8 expression in 20 benign mesothelial lesions (5 adenomatoid tumors, 5 well-differentiated papillary mesothelial tumors, and 10 peritoneal inclusion cysts) and 16 epithelioid peritoneal mesotheliomas. The 17 female and 3 male patients with benign mesothelial lesions ranged from 20 to 80 yr (median: 56.5 yr), while the 9 females and 7 males with mesothelioma ranged from 47 to 85 yr (median: 57.5 yr). SOX17 was positive in 5 (25%) benign lesions (2 adenomatoid tumors, 3 peritoneal inclusion cysts) and 2 (13%) mesotheliomas, while PAX8 stained 8 (40%) benign lesions (1 adenomatoid tumor, 1 well-differentiated papillary mesothelial tumor, 6 peritoneal inclusion cysts), and 2 (13%) mesotheliomas. Results for the 2 stains showed incomplete concordance, with agreement in 15 (75%) benign proliferations and 14 (88%) mesotheliomas. Our findings suggest that SOX17 positivity alone is insufficient to confirm a diagnosis of gynecologic carcinoma over a mesothelial proliferation and pathologists should exercise caution when these entities are diagnostic considerations.
Retroperitoneal Malakoplakia Mimicking Metastatic Disease
Authors: Dominguez Dylan , Eichhorn Joshua , Palot Manzil Fathima Fijula 
Published: October 2024

Abstract
Malakoplakia is a rare inflammatory granulomatous disease that can produce a tumor-like appearance in nearly any organ system. Imaging findings of malakoplakia overlap with malignancy and tissue sampling are typically required for definitive diagnosis. We present a case of a 66-year-old woman with a previous history of liver adenocarcinoma status post resection that subsequently developed an intensely FDG-avid retroperitoneal mass on surveillance imaging. CT-guided biopsy of the mass demonstrated Michaelis-Gutmann bodies, supporting the diagnosis of malakoplakia. The patient underwent antibiotic treatment with complete resolution of the mass.
Rare Gastric Metastasis of Lobular Type Breast Cancer Detected With 68Ga-FAPI-46 PET/CT
Authors: Akgun Elife , Şahin Omer Faruk , Baloglu Mehmetcan , Alcin Goksel , Yarikkaya Enver , Arslan Esra 
Published: October 2024

Abstract
Invasive lobular breast cancer (ILBC) is characterized with low tracer uptake on 18F-FDG PET images. ILBC metastasis to gastrointestinal tract is a rare clinic scenario. We present a case of ILBC who presented with gastric metastasis and diagnosed with 68Ga-FAPI-46 PET/CT and 18F-FDG PET/CT images.
Incidence and Risk Factors for Secondary Surgery and Amputation After Lower Extremity Limb Salvage
Authors: Brown Ciara , Ash Makenna , Menon Ambika , Knaus William , Hernandez-Irizarry Roberto , Ghareeb Paul 
Published: October 2024

Background
Traumatic defects of the lower extremity (LE) require robust soft tissue to cover critical structures and facilitate healing. Free tissue transfer (FTT) is often necessary when local tissue is inadequate. While much of the literature emphasizes free flap viability in successful limb salvage, there is limited understanding regarding the need for additional surgeries or eventual amputation. We investigated a single institution's limb salvage efforts to better understand the need for additional procedures.

Methods
All patients who underwent LE limb salvage were retrospectively reviewed from 2014 to 2022 at a single level 1 trauma center. Our primary clinical outcome was the incidence and indication of secondary surgeries following FTT.

Results
Ninety-two LE free flaps were performed during the study period. The mean age was 45 and majority were male. Seventy-two percent of flaps were fasciocutaneous while 28% were muscle flaps. Seventy-two percent of patients required a secondary surgery following FTT, with a mean of 7 total surgeries per salvage attempt. Ten percent of patients proceeded to amputation. Body mass index >30, higher frailty scores, flap type, and masquelet technique were significantly associated with subsequent amputation (P = 0.017, P = 0.024, P = 0.005, P = 0.04, respectively). Older age, the need for bony reconstruction, and longer period from injury to flap coverage were significantly associated with the need for secondary surgeries (P = 0.05, P < 0.001, and P = 0.22 respectively)

Conclusions
FTT is an important component of limb salvage. Patients undergoing limb salvage should be counseled on the need for secondary surgeries, as the process is often not complete following FTT. Furthermore, risk factors identified in this study may increase the likelihood of subsequent amputation. Thorough preoperative counseling is necessary to optimize the postoperative course and expectations in this population.
Physiological and Functional Restoration of the Modiolus Using a Double Tendon Sling in Patients With Full-Thickness Oral Defects
Authors: Maeda Taku , Hayashi Toshihiko , Ishikawa Kosuke , Miura Takahiro , Funayama Emi , Yamamoto Yuhei 
Published: October 2024

Background
Reconstruction of the oral modiolus should be considered for facial defects involving the lip and cheek. We have performed free flap reconstruction using a novel technique that includes a vertical and a horizontal sling for full-thickness defects involving the oral commissure.

Patients and Methods
We used a free radial forearm flap and the palmaris longus tendon to correct lip and cheek defects in 6 patients (3 men, 3 women; age, 55–84 years). The tendon was divided into 2 portions for use as the double sling. One sling was used to connect the upper and lower stumps of the orbicularis oris in the vertical direction and the other to connect the vertical sling and masseter muscle. The outcomes assessed were esthetic appearance and functional results.

Results
The facial defects ranged in size from 3.0 cm × 4.0 cm to 7.0 cm × 6.0 cm and the mucosal defects from 1.5 cm × 4.0 cm to 6.5 cm × 5.0 cm. The length of the harvested tendon ranged from 11.5 to 13.5 cm. All flaps survived without complications. Good esthetic outcomes were achieved (excellent facial appearance, n = 1; no lip deviation or drooping, n = 5). Functionally, all patients had acceptable mouth opening and were able to eat a regular diet.

Conclusions
Good physiological and functional results can be achieved using a double tendon sling for reconstruction of the modiolus in patients with full-thickness defects involving the oral commissure.
DNAm aging biomarkers are responsive: Insights from 51 longevity interventional studies in humans
Authors: Sehgal Raghav , Borrus Daniel , Kasamato Jessica , Armstrong Jenel F. , Gonzalez John , Markov Yaroslav , Priyanka Ahana , Smith Ryan , Carreras Natàlia , Dwaraka Varun B. ,   DNAm aging biomarkers community,   community Longevity interventional studies, Higgins-Chen Albert 
Published: October 2024

AbstractAging biomarkers can potentially allow researchers to rapidly monitor the impact of an aging intervention, without the need for decade-spanning trials, by acting as surrogate endpoints. Prior to testing whether aging biomarkers may be useful as surrogate endpoints, it is first necessary to determine whether they are responsive to interventions that target aging. Epigenetic clocks are aging biomarkers based on DNA methylation with prognostic value for many aging outcomes. Many individual studies are beginning to explore whether epigenetic clocks are responsive to interventions. However, the diversity of both interventions and epigenetic clocks in different studies make them difficult to compare systematically. Here, we curate TranslAGE-Response, a harmonized database of 51 public and private longitudinal interventional studies and calculate a consistent set of 16 prominent epigenetic clocks for each study, along with 95 other DNAm biomarkers that help explain changes in each clock. With this database, we discover patterns of responsiveness across a variety of interventions and DNAm biomarkers. For example, clocks trained to predict mortality or pace of aging have the strongest response across all interventions and show consistent agreement with each other, pharmacological and lifestyle interventions drive the strongest response from DNAm biomarkers, and study population and study duration are key factors in driving responsiveness of DNAm biomarkers in an intervention. Some classes of interventions such as TNF-alpha inhibitors have strong, consistent effects across multiple studies, while others such as senolytic drugs have inconsistent effects. Clocks with multiple sub-scores (i.e. “explainable clocks”) provide specificity and greater mechanistic insight into responsiveness of interventions than single-score clocks. Our work can help the geroscience field design future clinical trials, by guiding the choice of interventions, specific subsets of epigenetic clocks to minimize multiple testing, study duration, study population, and sample size, with the eventual aim of determining whether epigenetic clocks can be used as surrogate endpoints.
Exploring mechanisms of change in a Southern Ocean fishery with a co-produced network model
Authors: Ward Delphi , Hill Nicole , Melbourne-Thomas Jessica , Welsford Dirk , Arangio Rhys , McNeill Malcolm , Wotherspoon Simon , Ziegler Philippe , Corney Stuart 
Published: October 2024

AbstractA key challenge in planning long-term fisheries sustainability is overcoming uncertainties in predicted changes in target populations and catch rates in response to climate change and fishery trends. We combine transdisciplinary knowledge co-production and qualitative network modelling to advance system understanding and elucidate likely responses of a Patagonian toothfish fishery to future change. We co-developed a model of the Kerguelen Plateau biophysical-socioeconomic system with knowledge holders from industry and science; the first whole-of-system qualitative network model of intermediate complexity for this region. We present new approaches for dealing with uncertainty in network structure, and for investigating how perturbations propagate through a network. Using these tools, we found multiple potential pathways of decline for toothfish population and catch, but also some possible mechanisms of increase dependent on magnitude of certain effects. Our results highlight critical information gaps, including the potential role of scavenging benthos in fishery-ecosystem interactions and likely changes in the prey-field in response to warmer water, that require filling to improve predictions for toothfish populations and catch and forward planning for the fishery.
AlphaBridge: tools for the analysis of predicted macromolecular complexes
Authors: Álvarez-Salmoral Daniel , Borza Razvan , Xie Ren , Joosten Robbie P. , Hekkelman Maarten L. , Perrakis Anastassis 
Published: October 2024

AbstractArtificial intelligence (AI)-powered protein structure prediction methods have revolutionised how life scientists explore macromolecular function. Using AI to predict the structure of macromolecular complexes, is gaining attention for modelling known interactions and evaluating the likelihood of proteins forming multimers or interacting with other proteins or nucleic acids. There is a growing need for tools to efficiently evaluate these predicted models. We introduce new tools that use AlphaFold3’s “predicted local-distance difference test” (pLDDT), “predicted aligned error” (PAE), and “predicted distance error” (PDE) matrices in a graph-based community clustering approach to label sequence motifs involved in binary interactions. The resulting “interaction image” is processed through a multidimensional image algorithm to cluster interacting sequence motifs in three-dimensional binary interfaces. This method allows us to present the interaction information between multiple proteins and nucleic acids back to two-dimensional space using chord diagrams. These “AlphaBridge” diagrams summarise predicted interfaces and intermolecular interactions, including prediction confidence and sequence conservation scores. They are valuable for efficient screening of predictions, ranking, and scoring the confidence of predicted interactions, prior to more detailed (and resource intensive) analysis.
Generative Models Validation via Manifold Recapitulation Analysis
Authors: Lazzaro Nicolo’ , Leonardi Gianluca , Marchesi Raffaele , Datres Massimiliano , Saiani Anna , Tessadori Jacopo , Granados Alejandro , Henriksson Johan , Chierici Marco , Jurman Giuseppe , Tebaldi Toma , Sales Gabriele 
Published: October 2024

AbstractSummarySingle-cell transcriptomics increasingly relies on nonlinear models to harness the dimensionality and growing volume of data. However, most model validation focuses on local manifold fidelity (e.g., Mean Squared Error and other data likelihood metrics), with little attention to the global manifold topology these models should ideally be learning. To address this limitation, we have implemented a robust scoring pipeline aimed at validating a model’s ability to reproduce the entire reference manifold. The Python library Cytobench demonstrates this approach, along with Jupyter Notebooks and an example dataset to help users get started with the workflow. Manifold recapitulation analysis can be used to develop and assess models intended to learn the full network of cellular dynamics, as well as to validate their performance on external datasets.AvailabilityA Python library implementing the scoring pipeline has been made available via pip and can be inspected atGitHubalongside some Jupyter Notebooks demonstrating its application.Contactnlazzaro@fbk.euortoma.tebaldi@unitn.it