bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early-Onset Pancreatic Neuroendocrine Tumors
Authors: Pulvirenti Alessandra , Hauser Haley F. , Fiedler Laura M. , McIntyre Caitlin A. , Le Tiffany , Reidy-Lagunes Diane L. , Soares Kevin C. , Balachandran Vinod P. , Kingham T. Peter , D’Angelica Michael I. , Drebin Jeffrey A. , Jarnagin William R. , Raj Nitya , Wei Alice C. 
Published: June 2023

Background:
Early-Onset (EO) pancreatic neuroendocrine tumor (PanNET) is a rare disease but whether is clinically different from late-onset (LO) PanNET is unknown. Our study aimed to evaluate clinical differences and disease outcomes between EO- and LO-PanNET and to compare sporadic EO-PanNET with those with a hereditary syndrome (HS).

Methods:
Patients with localized PanNET who underwent pancreatectomy at Memorial Sloan Kettering between 2000-17 were identified. Those with metastatic disease and poorly differentiated tumors were excluded. EO-PanNET was defined as <50 and LO-PanNET >50 years of age at the time of diagnosis. Family history, and clinical and pathology characteristics were recorded.

Results:
Overall 383 patients were included, 107 (27.9%) with EO-PanNET. Compared with LO-PanNET, EO-PanNET were more likely to have a hereditary syndrome (2.2% vs. 16%, P<0.001) but had similar pathology features such as tumor grade (P=0.6), size (2.2 Vs. 2.3 cm, P=0.5) and stage of disease (P=0.8). Among patients with EO-PanNET those with HS had more frequently a multifocal disease (65% vs. 3.3%, P<0.001). With a median follow-up of 70 months (range 0-238), the 5-year cumulative incidence of recurrence after curative surgery was 19% (95%CI 12-28%) and 17% (95%CI 13-23%), in EO- and LO-PanNET (P=0.3). Five-year disease-specific survival was 99% (95%CI 98-100%) with no difference with respect to PanNET onset time (P=0.26)

Conclusion:
In this surgical cohort, we found that EO-PanNET is associated with hereditary syndromes but has pathological characteristics and oncological outcomes similar to LO-PanNET. These findings suggest that patients with EO-PanNET can be managed similarly to those with LO-PanNET.
Resolution of Secondary Hyperparathyroidism after Kidney Transplantation and the Effect on Graft Survival
Authors: Wang Rongzhi , Price Griffin , Disharoon Mitchell , Stidham Gabe , McLeod M. Chandler , McMullin Jessica Liu , Gillis Andrea , Fazendin Jessica , Lindeman Brenessa , Ong Song , Chen Herbert 
Published: June 2023

Objective:
Hyperparathyroidism (HPT) is nearly universal in patients with end-stage kidney disease. Kidney transplantation (KT) reverses HPT in many patients, but most studies have only focused on following calcium and not parathyroid hormone (PTH) levels. We sought to study the prevalence of persistent HPT post-KT at our center and its effect on graft survival.

Methods:
Patients who underwent KT from January 2015 to August 2021 were included and characterized by post-KT HPT status at the most recent follow-up: resolved (achieving normal PTH post-KT) versus persistent HPT. Those with persistent HPT were further stratified by the occurrence of hypercalcemia (normocalcemic versus hypercalcemic HPT). Patient demographics, donor kidney quality, PTH and calcium levels, and allograft function were compared between groups. Multivariable logistic regression and Cox regression with propensity score matching (PSM) were conducted.

Results:
Of 1554 patients, only 390 (25.1%) patients had resolution of renal HPT post-KT with a mean (±SD) follow-up length of 40±23 months. The median (IQR) length of HPT resolution was 5 (0-16) months. Of the remaining 1164 patients with persistent HPT post-KT, 806 (69.2%) patients had high PTH and normal calcium levels, while 358 (30.8%) patients had high calcium and high PTH levels. Patients with persistent HPT had higher parathyroid hormone (PTH) at the time of KT [403 (243 – 659) versus 277 (163 – 454) pg/mL, P<0.001] and were more likely to have received cinacalcet treatment before KT (34.9% vs. 12.3%, P<0.001). Only 6.3% of patients with persistent HPT received parathyroidectomy. Multivariable logistic regression showed race, cinacalcet use pre-KT, dialysis before KT, receiving an organ from a deceased donor, high PTH, and calcium levels at KT were associated with persistent HPT post-KT. After adjusting for patient demographics and donor kidney quality by PSM, persistent HPT (HR 2.5, 95% CI 1.1 – 5.7, P=0.033) was associated with a higher risk of allograft failure. Sub-analysis showed that both hypercalcemic HPT (HR 2.6, 95% CI 1.1 – 6.5, P=0.045) and normocalcemic HPT (HR 2.5, 95% CI 1.3-5.5, P=0.021) were associated with increased risk of allograft failure when compared to patients with resolved HPT.

Conclusion:
Persistent HPT is common (75%) after KT and is associated with a higher risk of allograft failure. PTH levels should be closely monitored after kidney transplantation so that patients with persistent HPT can be treated appropriately.
Research priorities in venous thromboembolism after trauma: Secondary analysis of the National Trauma Research Action Plan
Authors: Costantini Todd W. , Bulger Eileen , Price Michelle A. , Haut Elliott R. ,   the National Trauma Research Action Plan (NTRAP) Investigators Group
Published: June 2023

BACKGROUND
Venous thromboembolism (VTE) is a significant cause of morbidity and mortality during recovery from injury and can result in significant health care costs. Despite advances in the past several decades in our approach to VTE prophylaxis after injury, opportunities exist to improve the delivery and implementation of optimal VTE prophylaxis. Here, we aim to identify consensus research questions related to VTE across all National Trauma Research Action Plan (NTRAP) Delphi expert panels to further guide the research agenda aimed at preventing VTE after injury.

METHODS
This is a secondary analysis of consensus-based research priorities that were collected using a Delphi methodology by 11 unique NTRAP panels that were charged with unique topic areas across the spectrum of injury care. The database of questions was queried for the keywords “VTE,” “venous thromboembo,” and “DVT” and then grouped into relevant topic areas.

RESULTS
There were 86 VTE-related research questions identified across 9 NTRAP panels. Eighty-five questions reached consensus with 24 rated high priority; 60, medium priority; and 1, low priority. Questions related to the timing of VTE prophylaxis (n = 17) were most common, followed by questions related to risk factors for the development of VTE (n = 16), the effects of tranexamic acid on VTE (n = 11), the approach to dosing of pharmacologic prophylaxis (n = 8), and the pharmacologic prophylactic medication choice for optimal VTE prophylaxis (n = 6).

CONCLUSION
National Trauma Research Action Plan panelists identified 85 consensus-based research questions that should drive dedicated extramural research funding opportunities to support quality studies aimed at optimizing VTE prophylaxis after injury.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
Cancer “Avatars”: Patient-Derived Xenograft Growth Correlation with Postoperative Recurrence and Survival in Pancreaticobiliary Cancer
Authors: Lynch Isaac T , Abdelrahman Amro M , Alva-Ruiz Roberto , Fogliati Alessandro , Graham Rondell P , Smoot Rory , Truty Mark J 
Published: June 2023

BACKGROUND:
Pancreaticobiliary (PB) cancers are a diverse group of cancers with poor prognoses and high rates of recurrence after resection. Patient-derived xenografts (PDX), created from surgical specimens, provide a reliable preclinical research platform and high-fidelity cancer model from which to study these malignancies with consistent recapitulation of their original patient tumors in vivo. However, the relationship between PDX engraftment success (growth or no growth) and patient oncologic outcomes has not been well studied. We sought to evaluate the correlation between successful PDX engraftment and survival in several PB exocrine carcinomas, including the pancreatic and biliary tract.

STUDY DESIGN:
In accordance with IRB and Institutional Animal Care and Use Committee protocols and with appropriate consent and approval, excess tumor tissue obtained from surgical patients was implanted into immunocompromised mice. Mice were monitored for tumor growth to determine engraftment success. PDX tumors were verified to recapitulate their tumors of origin by a hepatobiliary pathologist. Xenograft growth was correlated with clinical recurrence and overall survival data.

RESULTS:
A total of 384 PB xenografts were implanted. The successful engraftment rate was 41% (158/384). We found that successful PDX engraftment was highly associated with both recurrence-free survival (p < 0.001) and overall survival (p < 0.001) outcomes. Successful PDX tumor generation occurs significantly in advance of clinical recurrences in their corresponding patients (p < 0.001).

CONCLUSIONS:
Successful PB cancer PDX models predict recurrence and survival across tumor types and may provide critical lead time to alter patients’ surveillance or treatment plans before cancer recurrence.
Going through phages: a computational approach to revealing the role of prophage in Staphylococcus aureus
Authors: Sweet Tyrome , Sindi Suzanne , Sistrom Mark 
Published: June 2023

Prophages have important roles in virulence, antibiotic resistance, and genome evolution in

Staphylococcus aureus

. Rapid growth in the number of sequenced

S. aureus

genomes allows for an investigation of prophage sequences at an unprecedented scale. We developed a novel computational pipeline for phage discovery and annotation. We combined PhiSpy, a phage discovery tool, with VGAS and PROKKA, genome annotation tools to detect and analyse prophage sequences in nearly 10 011

S

.

aureus

genomes, discovering thousands of putative prophage sequences with genes encoding virulence factors and antibiotic resistance. To our knowledge, this is the first large-scale application of PhiSpy on a large-scale set of genomes (10 011

S

.

aureus

). Determining the presence of virulence and resistance encoding genes in prophage has implications for the potential transfer of these genes/functions to other bacteria via transduction and thus can provide insight into the evolution and spread of these genes/functions between bacterial strains. While the phage we have identified may be known, these phages were not necessarily known or characterized in

S. aureus

and the clustering and comparison we did for phage based on their gene content is novel. Moreover, the reporting of these genes with the

S. aureus

genomes is novel.
Purpura fulminans secondary to Capnocytophaga canimorsus bacteraemia following a dog bite: A case report and review of literature
Authors: Killington Kieran , Lee Nathaniel , Asher Radha , Farrant Olivia , Stone Neil 
Published: June 2023

Introduction. Infection due to

Capnocytophaga canimorsus

may result in a wide variety of clinical presentations. We present a case of life-threatening

Capnocytophaga canimorsus

infection with evolution of ecchymosis to purpura fulminans.

Case description. We present a case of a 43-year-old male with a history of excessive alcohol consumption who presented with features of sepsis following a dog bite. This was associated with a striking, widespread purpuric rash. A causative pathogen,

C. canimorsus

was identified through blood culture and 16S RNA sequencing. His initially purpuric rash underwent bullous transformation and was diagnosed clinically as purpura fulminans, confirmed on skin biopsy. He made a full recovery with prompt antimicrobial therapy, initially with co-amoxiclav but escalated to clindamycin and meropenem due to clinical deterioration and concerns of beta-lactamase resistance.

Discussion. β-Lactamase producing

Capnocytophaga

strains are of increasing concern. This particular concern is reflected in our case as 5 days into treatment with β-lactamase inhibitor combination therapy the patients clinical condition deteriorated but demonstrably improved on switching to a carbapenem.
The development of biopsy proven purpura fulminans in this immunocompetent case is a rare severe manifestation of the previously reported manifestation of disseminated intravascular coagulation (DIC) in

Capnocytophaga

bacteraemia. The case reported describes characteristics common with other DIC presentations such as the presence of clinical risk factors (history of excessive alcohol consumption) and symmetrical involvement. However, an unusual feature in that initial purpuric lesions were followed by the development of a bullous appearance and peripheral necrotic features concerning for purpura fulminans and confirmed with skin biopsy.
Functional annotation with expression validation identifies novel metastasis-relevant genes from post-GWAS risk loci in sporadic colorectal carcinomas
Authors: Thean Lai Fun , Wong Michelle , Lo Michelle , Tan Iain , Wong Evelyn , Gao Fei , Tan Emile , Tang Choong Leong , Cheah Peh Yean 
Published: June 2023

AbstractColorectal cancer (CRC) is the third highest incidence cancer and leading cause of cancer mortality worldwide. Metastasis to distal organ is the major cause of cancer mortality. However, the underlying genetic factors are unclear. This study aims to identify metastasis-relevant genes and pathways for better management of metastasis-prone patients. Multiple lines of evidence have indicated that germline variants play important role in shaping the somatic (tumor) genome. A case-case genome-wide association study comprising 2677 sporadic Chinese CRC cases (1282 metastasis-positive vs 1395 metastasis-negative) was performed using the Human SNP6 microarray platform and analyzed with the correlation/trend test based on the additive model. Single nucleotide polymorphism (SNP) variants with association testing -log10p-value ≥ 5 were imported into Functional Mapping and Annotation (FUMA) for functional annotation which uncovered glycolysis as the top hallmark geneset. Transcripts from two of the five genes profiled, HAX1 and HMMR, were significantly down-regulated in the metastasis-positive tumors. In contrast to disease-risk variants with minimal impact on survival, HAX1 appeared to act synergistically with HMMR in significantly impacting metastasis-free survival. Furthermore, examining the subtype datasets with FUMA and Ingenuity Pathway identified distinct pathways demonstrating sexual dimorphism in CRC metastasis. Combining genome-wide association testing with in silico functional annotation and wet-bench validation identified metastasis-relevant genes that could serve as features to develop subtype-specific metastasis-risk signatures for tailored management of Stage I-III CRC patients.
Genome-wide meta-analysis of CSF biomarkers in Alzheimer’s disease and Parkinson’s disease cohorts
Authors: Ta Michael , Blauwendraat Cornelis , Antar Tarek , Leonard Hampton L , Singleton Andrew B. , Nalls Mike A. , Iwaki Hirotaka ,   Alzheimer’s Disease Neuroimaging Initiative (ADNI),   the Fox Investigation for New Discovery of Biomarkers
Published: June 2023

AbstractBackgroundAmyloid beta (Aβ), phosphorylated tau (p-tau), and total tau (t-tau) in cerebrospinal fluid are established biomarkers for Alzheimer’s disease (AD). In other neurodegenerative diseases, such as Parkinson’s disease (PD), these biomarkers have also been found to be altered, and the molecular mechanisms responsible for these alterations are still under investigation. Moreover, the interplay between these mechanisms and the diverse underlying disease states remains to be elucidated.ObjectivesTo investigate genetic contributions to the AD biomarkers and assess the commonality and heterogeneity of the associations per underlying disease status.MethodsWe conducted GWAS for the AD biomarkers on subjects from the Parkinson’s Progression Markers Initiative (PPMI), the Fox Investigation for New Discovery of Biomarkers (BioFIND), and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and meta-analyzed with the largest AD GWAS.[7] We tested heterogeneity of associations of interest between different disease statuses (AD, PD, and control).ResultsWe observed three GWAS signals: theAPOElocus for Aβ, the 3q28 locus betweenGEMC1andOSTNfor p-tau and t-tau, and the 7p22 locus (top hit: rs60871478, an intronic variant forDNAAF5, also known asHEATR2) for p-tau. The 7p22 locus is novel and co-localized with the brainDNAAF5expression. While no heterogeneity from underlying disease status was observed for the above GWAS signals, some disease risk loci suggested disease specific associations with these biomarkers.ConclusionsOur study identified a novel association at the intronic region ofDNAAF5associated with increased levels of p-tau across all diseases. We also observed some disease specific genetic associations with these biomarkers.
Prediction models for post-discharge mortality among under-five children with suspected sepsis in Uganda: A multicohort analysis
Authors: Wiens Matthew O , Nguyen Vuong , Bone Jeffrey N , Kumbakumba Elias , Businge Stephen , Tagoola Abner , Sherine Sheila Oyella , Byaruhanga Emmanuel , Ssemwanga Edward , Barigye Celestine , Nsungwa Jesca , Olaro Charles , Ansermino J Mark , Kissoon Niranjan , Singer Joel , Larson Charles P , Lavoie Pascal M , Dunsmuir Dustin , Moschovis Peter P , Novakowski Stefanie , Komugisha Clare , Tayebwa Mellon , Mwesigwa Douglas , West Nicholas , Knappett Martina , Mugisha Nathan Kenya , Kabakyenga Jerome 
Published: June 2023

AbstractBackgroundIn many low-income countries, more than five percent of hospitalized children die following hospital discharge. The identification of those at risk has limited progress to improve outcomes. We aimed to develop algorithms to predict post-discharge mortality among children admitted with suspected sepsis.MethodsFour prospective cohort studies were conducted at six hospitals in Uganda between 2012 and 2021. Death occurring within six months of discharge was the primary outcome. Separate models were developed for children 0-6 months of age and for those 6-60 months of age, based on candidate predictors collected at admission. Within each age group, three models were derived, each with a maximum of eight variables based on variable importance. Deriving parsimonious models with different sets of predictors was prioritized to improve usability and support implementation in settings where some data elements are unavailable. All models were internally validated using 10-fold cross validation.Findings8,810 children were prospectively enrolled, of whom 470 died in hospital and 161 (1·9%) were lost to follow-up; 257 (7·7%) and 233 (4·8%) post-discharge deaths occurred in the 0-6-month and 6-60-month age groups, respectively. The primary models had an area under the receiver operating characteristic curve (AUROC) of 0·77 (95%CI 0·74-0·80) for 0-6-month-olds and 0·75 (95%CI 0·72-0·79) for 6-60-month-olds; mean AUROCs among the 10 cross-validation folds were 0·75 and 0·73, respectively. Calibration across risk strata were good with Brier scores of 0·07 and 0·04, respectively. The most important variables included anthropometry and oxygen saturation. Additional variables included duration of illness, jaundice-age interaction, and a bulging fontanelle among 0-6-month-olds; and prior admissions, coma score, temperature, age-respiratory rate interaction, and HIV status among 6-60-month-olds.InterpretationSimple prediction models at admission with suspected sepsis can identify children at risk of post-discharge mortality. Further external validation is recommended for different contexts. Models can be integrated into existing processes to improve peri-discharge care as children transition from the hospital to the community.FundingGrand Challenges Canada (#TTS-1809-1939), Thrasher Research Fund (#13878), BC Children’s Hospital Foundation, and Mining4Life.
Vascular risk factors modulate gender-specific aging of brain white matter structural network
Authors: Chen Haojie , Huang Weijie , Dong Xinyi , Feng Guozheng , Wang Yiwen , Liu Zhenzhao , Ma Shuning , Peng Junjie , Su Li , Shu Ni 
Published: June 2023

AbstractVascular risk factors (VRFs) are known to increase risk for cerebrovascular disease and dementia, such as Alzheimer’s disease that is described as a dysconnectivity syndrome. The gender-related evidence on associations between VRFs and white matter (WM) structural network in large community-dwelling populations across middle and older age will contribute to understanding the biological underpinnings of sex and gender considerations in dementia. Based on 17,954 participants from the UK Biobank, we present the relationship between VRFs and WM network architecture (measured with network integration and segregation) in different gender groups. First, females exhibit lower network architecture and experience an accelerated decline earlier than males. Second, network integration is more sensitive to VRFs than segregation, with diabetes, hypertension, and excessive alcohol consumption having the greatest impact. Third, we found greater susceptibility of network architecture to VRFs in males, as well as female-preferred effects on regional integration of obesity, particularly on the subcortical structure and occipital lobe. Finally, higher combined risk was associated with more disrupted network architecture particularly on temporal and frontal lobe, as well as lower processing speed and working memory in both genders. Our findings provide new insights into understanding the relationship between VRFs and WM network architecture, guiding interventions to promote successfully cognitive aging and highlighting the importance of considering gender-specific effects in future research.
High-Resolution Additive Manufacturing of a Biodegradable Elastomer with a Low-Cost LCD 3D Printer
Authors: Karamzadeh Vahid , Shen Molly L. , Ravanbakhsh Hossein , Sohrabi-Kashani Ahmad , Savoji Houman , Radisic Milica , Juncker David 
Published: June 2023

AbstractArtificial organs and organs-on-a-chip are of great clinical and scientific interest and have recently been made by additive manufacturing, but depend on, and benefit from, biocompatible, biodegradable, and soft materials. Poly(octamethylene maleate (anhydride) citrate (POMaC) meets these criteria and has gained popularity, and as in principle, it can be photocured and is amenable to vat-photopolymerization (VP) 3D printing, but only low-resolution structures have been produced so fa. Here, we introduce a VP-POMaC ink and demonstrate 3D printing of high resolution (80 µm) and complex 3D structures using low-cost (∼US$300) liquid-crystal display (LCD) printers. The ink includes POMaC, a diluent and porogen additive to reduce viscosity within the range of VP, and a crosslinker to speed up reaction kinetics. The mechanical properties of the cured ink were tuned to match the elastic moduli of different tissues simply by varying the porogen concentration. The biocompatibility was assessed by cell culture which yielded 80% viability and the potential for tissue engineering illustrated with a 3D printed gyroid seeded with cells. VP-POMaC and low-cost LCD printers make the additive manufacturing of high resolution, elastomeric, and biodegradable constructs widely accessible, paving the way for a myriad of applications in tissue engineering, implants, organ-on-a-chip, wearables, and soft robotics.