bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low-grade Hidradenocarcinomas
Authors: Plaza Jose A. , Wakely Paul , Roman Jorge , Gru Alejandro A. , Sangueza J. Martin , Davey Jonathan , Brenn Thomas 
Published: June 2023

Hidradenocarcinomas are rare cutaneous adnexal malignancies with sweat gland differentiation that can show a broad spectrum of histomorphologic appearances, ranging from low to high grade. The diagnosis of low-grade hidradenocarcinoma can be challenging and may be mistaken for benign hidradenomas, especially on superficial and partial samples. We performed a retrospective analysis of 16 low-grade hidradenocarcinomas, obtained from 4 large academic institutions. All neoplasms presented clinically as nodular lesions that ranged in size from 1.5 to 6.0 cm. All patients were adults and their age ranged from 33 to 74 years of age. All cases shared features similar to hidradenomas in the surface and mid portion of the tumors and all tumors had 1 or more histomorphologic clues to malignancy, including the presence of an asymmetric and infiltrative growth pattern (especially at the base of the tumors), perineurial invasion, and a desmoplastic stromal reaction. In the tumors evaluated for immunohistochemistry, the tumor cells were positive for p63, EMA, AE1/AE3, MNF116, and CK7. Three patients underwent sentinel lymph node biopsy, and 2 cases showed metastatic disease to regional lymph nodes. All cases (including the 2 cases that had regional lymph node metastasis), showed no local recurrence or distant metastasis observed after a complete re-excision of the tumors (follow-up range from 6 to 72 mo). Our study highlights the salient clinical and histopathologic features of low-grade hidradenocarcinomas and emphasizes the potential diagnostic pitfalls in distinguishing this entity from other neoplasms. Our results indicate that a combination of thorough histopathologic inspection is necessary to support the diagnosis of this rare neoplasm. These tumors can be exceedingly difficult to diagnose and awareness of the subtle features of low-grade hidradenocarcinoma is of importance are as it remains a diagnostic challenge for practicing pathologists.
Quantitative sensory testing as an assessment tool to predict the response to standard pain treatment in knee osteoarthritis: a systematic review and meta-analysis
Authors: Petersen Kristian Kjær-Staal , Kilic Kübra , Hertel Emma , Sejersgaard-Jacobsen Trine Hyttel , Jørgensen Marlene Kanstrup , Troelsen Anders , Arendt-Nielsen Lars , Boye Larsen Dennis 
Published: June 2023

Abstract
Emerging evidence suggest that quantitative sensory testing (QST) may predict the treatment response to pain-relieving therapies. This systematic review and meta-analysis focus on the predictive value of QST for pain management of knee osteoarthritis (OA). MEDLINE and EMBASE were systematically searched for all studies from year 2000 to 2023 on pretreatment QST and treatment of OA including surgical, pharmaceutical, and nonsurgical and nonpharmaceutical therapies. Preclinical studies and reviews were excluded. The systematic review followed the PRISMA guidelines and was pre-registered on the Open Science Framework website (link: https://osf.io/4FETK/, Identifier: DOI 10.17605/OSF.IO/4FETK). Meta-analysis were conducted to demonstrate the strength of the pre-treatment QST predictions on pain outcomes after OA treatments. Sixteen surgical (all on total knee arthroplasty [TKA], N = 1967), 5 pharmaceutical (4 on non-steroidal anti-inflammatory drugs [NSAIDs], N = 271), and 4 exercise-based therapy studies (N = 232) were identified. Pretreatment QST parameters predicted pain-relieving treatment outcomes in 81% of surgical, 100% of pharmaceutical, and 50% of exercise-based therapy studies. Meta-analyses found pretreatment QST profiles to predicted pain outcomes after TKA (random effects: 0.309, 95% confidence interval [CI]: 0.206–0.405, P < 0.001), NSAIDs (random effects: 0.323, 95% CI: 0.194–0.441, P < 0.001), and exercise-based therapies (random effects: 0.417, 95% CI: 0.138–0.635, P = 0.004). The overall risk of bias for the included studies was low to moderate. This systematic review and meta-analysis demonstrate weak-to-moderate associations between pretreatment QST and pain outcomes after standard OA pain treatments. Based on this work, it is hypothesized that a subset of specific pain sensitive patients with OA exist and that these patients do not respond adequately to standard OA pain treatments.
Unexpected Origin of Lung Metastases
Authors: Zhou Wenlan , Wu Hubing 
Published: June 2023

Abstract
A 49-year-old woman was referred to our hospital due to suspected lung metastases for 1 month. She had a history of thyroid micropapillary carcinoma and uterine leiomyomas. An 18F-FDG PET/CT scan, which was performed to search the source of the presumed metastasis of the disease, showed multiple lung metastases and 2 18F-FDG–avid foci in the thyroid and colon. Biopsy of lung and resection of colon lesions were then performed, and the disease was finally identified to be rare primary colon leiomyosarcoma with multiple lung metastases.
Multiple-Organ Involvement of Malakoplakia Mimicking Malignant Neoplasms on 18F-FDG PET/CT
Authors: Jiao Benzheng , Liu Shanshan , Ma Xiaobo , Wong Chinting , Zhao Hongguang 
Published: June 2023

Abstract
Abdominal contrast-enhanced CT was performed in a 61-year-old man with difficulties of urination and defecation for 4 months, which revealed huge rectal masses involving multiple adjacent organs, suspected as malignant lesions. 18F-FDG PET/CT was subsequently performed for staging. The images showed intense FDG uptake and slightly hyperdense masses involving rectum, bladder, prostate, left ureter, and the anterior abdominal wall at the level of the pelvic cavity. Histopathological examination confirmed the masses were due to malakoplakia, which displayed as abundant von Hansemann cells aggregated and infiltrated in lesions, with distinctive cytoplasmic inclusions termed Michaelis-Gutmann bodies.
Unusual Case of Missed Penile Metastases on 68Ga-PSMA PET/CT
Authors: Caputo Sydney A. , Blair Graham , Hawkins Madeline , Harris Kendra , Sartor Oliver 
Published: June 2023

Abstract
A 75-year-old man with a history of previously treated localized prostate cancer and prostate-specific antigen of 4.86 ng/mL was referred for a 68Ga–prostate-specific membrane antigen PET/CT. PET imaging was reported to be negative. After subsequent review and re-read of the scan, prostate-specific membrane antigen imaging revealed uptake along the penile shaft (SUVmax of 14.7). MRI was compatible with tumor. Penile metastases from prostate cancer, although uncommon, do occur and readers are encouraged to distinguish penile metastatic uptake from residual urine in the urethra.
FEASIBILITY OF A SELF-MANAGEMENT INTERVENTION TO IMPROVE MOBILITY IN THE COMMUNITY AFTER STROKE (SIMS): A MIXED-METHODS PILOT STUDY
Authors: Sahely Ahmad , Sintler Carron , Soundy Andrew , Rosewilliam Sheeba 
Published: June 2023

AbstractObjectiveTo evaluate the feasibility of implementing a self-management intervention to improve mobility in the community for stroke survivors.MethodsA sequential mixed methods design was used (a pilot randomised controlled trial and focus groups). Participants were adult stroke survivors within six months post discharge from hospital with functional and cognitive capacity for self-management. The intervention included education sessions, goal setting and action planning, group sessions, self-monitoring and follow up. The control group received usual care and both groups enrolled for 3 months in the study. Feasibility outcomes (recruitment and retention rates, randomisation and blinding, adherence to the intervention, collection of outcome measures, and the fidelity and acceptability of the intervention). Participants assessed at baseline, 3 months and 6 months for functional mobility and walking, self-efficacy, goal attainment, cognitive ability, and general health. A descriptive analysis was done for quantitative data and content analysis for the qualitative data. Findings of quantitative and qualitative data were integrated to present the final results of the study.ResultsTwenty-four participants were recruited and randomised into two groups (12 each). It was feasible to recruit from hospital and community and to deliver the intervention remotely. Randomisation and blinding were successful. Participants were retained (83%) at 3 months and (79.2%) at 6 months assessments. Adherence to the intervention varied due to multiple factors. Focus groups discussed participants’ motivations for joining the programme, their perspectives on the intervention (fidelity and acceptability) and methodology, perceived improvements in mobility, facilitators and challenges for self-management, and suggestions for improvement.ConclusionThe self-management intervention seems feasible for implementation for stroke survivors in the community. Participants appreciated the support provided and perceived improvement in their mobility. The study was not powered enough to draw a conclusion about the efficacy of the program and a future full-scale study is warranted.
Non-Invasive Mechanical Ventilation reduces the Motor Decline in Amyotrophic Lateral Sclerosis
Authors: Grassano Maurizio , Koumantakis Emanuele , Manera Umberto , Canosa Antonio , Vasta Rosario , Francesca Palumbo , Fuda Giuseppe , Salamone Paolina , Marchese Giulia , Casale Federico , Charrier Lorena , Mora Gabriele , Moglia Cristina , Calvo Andrea , Chiò Adriano 
Published: June 2023

AbstractBackgroundNon-invasive mechanical ventilation (NIMV) improves Amyotrophic Lateral Sclerosis (ALS) quality of life and survival. However, data about its effect on disease progression are still lacking.ObjectiveTo test whether NIMV use changed the rate of functional decline among ALS patients.MethodsIn this retrospective observational study, we included 465 ALS patients followed up at the ALS Center in Turin, Italy, who underwent NIMV during the disease course. The primary outcome was the change in functional decline after NIMV initiation when adjusting for covariates. Functional decline was based on the non-respiratory items of the ALS Functional Rating Score – Revised (ALSFRS-R).ResultsA slower progression of functional decline followed NIMV initiation (mean improvement 0.13, 95%CI 0.11 to 0.16, p<0.001) regardless of sex, age at diagnosis, and disease duration prior to NIMV initiation. Indeed, the disease stage at NIMV initiation (early or advanced) did not influence the results. Respiratory support exerts its slowing effect mainly on the progression of spinal motor function.ConclusionsWe proved that NIMV influences the rate of motor progression in ALS. This result was not a consequence of the ALSFRS-R floor effect. The functional decline slowed after starting NIMV independently of the site of disease onset. Our results reinforce the importance of not delaying NIMV initiation in all ALS patients. NIMV-induced slowing of disease progression should also be accounted for when evaluating clinical trial outcomes.
Discovery of prognostic and treatment predictive biomarkers in recently diagnosed type 1 diabetes patients treated with anti TNFα
Authors: Kostense S , Klap Jaco M , Ashoor H , Yang R , Weverling GJ , Sweet K , Rigby MR , Hedrick JA 
Published: June 2023

AbstractObjectiveThe T1GER study showed that treatment with the TNFα inhibitor golimumab in recently diagnosed type 1 diabetes patients showed better preservation of endogenous insulin production than placebo. However, considerable variation was observed among subjects. Therefore, a range of biomarkers were investigated for their potential to predict treatment response to golimumab.Research Design and MethodsBaseline blood samples from 79 subjects were tested for autoantibodies, microRNA, metabolites, lipids, inflammatory proteins, and clinical chemistry. Univariate analysis was used to identify biomarkers that correlated with C-peptide change. Multivariate analysis was performed to establish a biomarker algorithm predicting the C-peptide response during the study.ResultsMultivariate analysis showed that baseline metabolites and miRNAs best predicted C- peptide responses both for placebo and treatment arms. Lipids, and inflammatory proteins were moderately predictive, whereas autoantibodies and clinical chemistry showed little predictive value.An optimal model combining selected clinical variables and metabolites showed a correlation between predicted and observed C-peptide responses for the overall study up to 52 weeks, with an R2of 0.85. An LOOCV model was developed as a surrogate validation test, resulting in an R2of 0.69 overall, and an R2of 0.76 specifically predicting C-peptide responses at week 38.ConclusionsThe exploratory analysis of the T1GER study resulted in a set of baseline biomarkers with promising performance in predicting future C-peptide responses during the study. If validated in independent cohorts, these prognostic and predictive biomarkers and algorithm carry significant translational impacts that can assist clinicians in making treatment decisions.
Multivariable model of postoperative delirium in cardiac surgery patients: proteomic and demographic contributions
Authors: Gonçalves MCB , Khera T , Otu HH , Narayanan S , Dillon ST , Shanker A , Gu X , Jung Y , Ngo LH , Marcantonio ER , Libermann TA , Subramaniam B 
Published: June 2023

ABSTRACTBackgroundDelirium following cardiac surgery is common, morbid, and costly, but may be prevented with risk stratification and targeted intervention. Preoperative protein signatures may identify patients at increased risk for worse postoperative outcomes, including delirium. In this study, we aimed to identify plasma protein biomarkers and develop a predictive model for postoperative delirium in older patients undergoing cardiac surgery, while also uncovering possible pathophysiological mechanisms.MethodsSOMAscan analysis of 1,305 proteins in the plasma from 57 older adults undergoing cardiac surgery requiring cardiopulmonary bypass was conducted to define delirium-specific protein signatures at baseline (PREOP) and postoperative day 2 (POD2). Selected proteins were validated in 115 patients using the ELLA multiplex immunoassay platform. Proteins were combined with clinical and demographic variables to build multivariable models that estimate the risk of postoperative delirium and bring light to the underlying pathophysiology.ResultsA total of 115 and 85 proteins from SOMAscan analyses were found altered in delirious patients at PREOP and POD2, respectively (p<0.05). Using four criteria including associations with surgery, delirium, and biological plausibility, 12 biomarker candidates (Tukey’s fold change (|tFC|)>1.4, Benjamini-Hochberg (BH)-p<0.01) were selected for ELLA multiplex validation. Eight proteins were significantly altered at PREOP, and seven proteins at POD2 (p<0.05), in patients who developed postoperative delirium compared to non-delirious patients. Statistical analyses of model fit resulted in the selection of a combination of age, sex, and three proteins (angiopoietin-2 (ANGPT2); C-C motif chemokine 5 (CCL5); and metalloproteinase inhibitor 1 (TIMP1); AUC=0.829) as the best performing predictive model for delirium at PREOP. The delirium-associated proteins identified as biomarker candidates are involved with inflammation, glial dysfunction, vascularization, and hemostasis, highlighting the multifactorial pathophysiology of delirium.ConclusionOur study proposes a model of postoperative delirium that includes a combination of older age, female sex, and altered levels of three proteins. Our results support the identification of patients at higher risk of developing postoperative delirium after cardiac surgery and provide insights on the underlying pathophysiology.ClinicalTrials.gov(NCT02546765).
EuroQol-5D-3L in Long Covid patients After Supplementation with EchA Marine®, a Sea Urchin Eggs Extract: a double-blinded, multicentrical study
Authors: Brichetti V , Rubilar T. , Tejada J. , Montecino P. , Crespi-Abril A. , Barbieri E , de la Rosa N , Iriarte-Vazquez J. , Jajati N. , Volonteri C. , Sivori M. , de Larrañaga G. , Saldarini F. 
Published: June 2023

AbstractPatients with Long COVID experience a significant decrease in their quality of life and the lack of effective treatment represents an unmet need in medical care and patient health. One proposed strategy for treating Long COVID is to increase the body’s ability to restore immune balance by controlling inflammation with anti-inflammatory substances. For this reason, the aim of this double-blind study was to evaluate the supplementation of patients with EchA Marine®, a dietary supplement based on sea urchin eggs rich in Echinochrome A. This compound has demonstrated anti-inflammatory and antioxidant properties by activating the metabolism of glutathione and improving mitochondrial mass and performance. The EuroQol 5-Dimension (EQ-5D) is a standardized questionnaire assessing five dimensions of health: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression used as an instrument to measure health-related quality of life in clinical and economic studies. In this multicenter, double-blind, intervention study, we have demonstrated that the dietary supplement EchA Marine®can significantly enhance the quality of life of these patients, particularly in pain and discomfort; notably improving their quality of life and daily activity’s ability. EchA Marine®is an effective treatment option for Long COVID patients and with further research its efficacy could be further strengthened.
Genetic and functional diversity help explain pathogenic, weakly pathogenic, and commensal lifestyles in the genusXanthomonas
Authors: Pena Michelle M. , Bhandari Rishi , Bowers Robert M. , Weis Kylie , Newberry Eric , Wagner Naama , Pupko Tal , Jones Jeffrey B. , Woyke Tanja , Vinatzer Boris A. , Jacques Marie-Agnès , Potnis Neha 
Published: June 2023

AbstractThe genusXanthomonashas been primarily studied for pathogenic interactions with plants. However, besides host and tissue specific pathogenic strains, this genus also comprises nonpathogenic strains isolated from a broad range of hosts, sometimes in association with pathogenic strains, and other environments, including rainwater. Based on their incapacity or limited capacity to cause symptoms on the host of isolation, nonpathogenic xanthomonads can be further characterized as commensal and weakly pathogenic. This study aimed to understand the diversity and evolution of nonpathogenic xanthomonads compared to their pathogenic counterparts based on their co-occurrence and phylogenetic relationship and to identify genomic traits that form the basis of a life-history framework that groups xanthomonads by ecological strategies. We sequenced genomes of 83 strains spanning the genus phylogeny and identified eight novel species, indicating unexplored diversity. While some nonpathogenic species have experienced a recent loss of a type III secretion system, specifically, thehrp2cluster, we observed an apparent lack of association of thehrp2cluster with lifestyles of diverse species. We gathered evidence for gene flow among co-occurring pathogenic and nonpathogenic strains, suggesting the potential of nonpathogenic strains to act as a reservoir of adaptive traits for pathogenic strains and vice versa. We further identified traits enriched in nonpathogens that suggest a strategy of stress tolerance, rather than avoidance, during their association with a broad range of host plants.
Identifying modifiable comorbidities of schizophrenia by integrating electronic health records and polygenic risk
Authors: Vessels Tess , Strayer Nicholas , Choi Karmel W. , Lee Hyunjoon , Zhang Siwei , Han Lide , Morley Theodore J. , Smoller Jordan W. , Xu Yaomin , Ruderfer Douglas M. 
Published: June 2023

AbstractPatients with schizophrenia have substantial comorbidity contributing to reduced life expectancy of 10-20 years. Identifying which comorbidities might be modifiable could improve rates of premature mortality in this population. We hypothesize that conditions that frequently co-occur but lack shared genetic risk with schizophrenia are more likely to be products of treatment, behavior, or environmental factors and therefore potentially modifiable. To test this hypothesis, we calculated phenome-wide comorbidity from electronic health records (EHR) in 250,000 patients in each of two independent health care institutions (Vanderbilt University Medical Center and Mass General Brigham) and association with schizophrenia polygenic risk scores (PRS) across the same phenotypes (phecodes) in linked biobanks. Comorbidity with schizophrenia was significantly correlated across institutions (r = 0.85) and consistent with prior literature. After multiple test correction, there were 77 significant phecodes comorbid with schizophrenia. Overall, comorbidity and PRS association were highly correlated (r = 0.55, p = 1.29×10−118), however, 36 of the EHR identified comorbidities had significantly equivalent schizophrenia PRS distributions between cases and controls. Fifteen of these lacked any PRS association and were enriched for phenotypes known to be side effects of antipsychotic medications (e.g., “movement disorders”, “convulsions”, “tachycardia”) or other schizophrenia related factors such as from smoking (“bronchitis”) or reduced hygiene (e.g., “diseases of the nail”) highlighting the validity of this approach. Other phenotypes implicated by this approach where the contribution from shared common genetic risk with schizophrenia was minimal included tobacco use disorder, diabetes, and dementia. This work demonstrates the consistency and robustness of EHR-based schizophrenia comorbidities across independent institutions and with the existing literature. It identifies comorbidities with an absence of shared genetic risk indicating other causes that might be more modifiable and where further study of causal pathways could improve outcomes for patients.
Endodermal cells use contact inhibition of locomotion to achieve uniform cell dispersal during zebrafish gastrulation
Authors: LaBelle Jesselynn , Wyatt Tom , Woo Stephanie 
Published: June 2023

AbstractThe endoderm is one of the three primary germ layers that ultimately gives rise to the gastrointestinal and respiratory epithelia and other tissues. In zebrafish and other vertebrates, endodermal cells are initially highly migratory with only transient interactions among one other, but later converge together to form an epithelial sheet. Here, we show that during their early, migratory phase, endodermal cells actively avoid each other through contact inhibition of locomotion (CIL), a characteristic response consisting of 1) actin depolymerization and membrane retraction at the site of contact, 2) preferential actin polymerization along a cell-free edge, and 3) reorientation of migration away from the other cell. We found that this response is dependent on the Rho GTPase RhoA. Expression of dominant-negative (DN) RhoA attenuated migration reorientation after cell-cell contact and increased the amount of time cells spent in contact with each other — behaviors consistent with a loss of CIL. Computational modeling predicted that CIL is required to achieve the efficient and uniform dispersal characteristic of endodermal cells. Consistent with our model, we found that loss of CIL via DN RhoA expression resulted in irregular clustering of cells within the endoderm. Finally, using a combination of pharmacological and genetic perturbations, we identify EphA2 as the cell surface receptor mediating endodermal CIL. Together, our results suggest that endodermal cells use EphA2-and RhoA-dependent CIL as a cell dispersal and spacing mechanism, demonstrating how tissue-scale patterns can emerge from local cell-cell interactions.