bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic Neuroendocrine Tumors
Authors: Lee Sara , Maegawa Felipe B. , Joseph Sharon , Alvarado Luis A. , Mendoza-Ladd Antonio , Elhanafi Sherif , Philipovskiy Alexander , Tyroch Alan H. , Konstantinidis Ioannis T. 
Published: May 2022

Objectives
During the last decades, significant progress has been made in the management of patients with pancreatic neuroendocrine tumors (pNETs). It is unclear how the type of the treating health care facility alters patient outcomes.

Methods
Data from pNETs reported to the National Cancer Database between 2004 and 2016 were examined. Types of institutions were as follows: academic/research cancer program (ARP), comprehensive community cancer program (CCCP), integrated network cancer program (INCP), and community cancer program (CCP).

Results
A total of 17,887 patients with pNETs were analyzed. Treatment at ARPs was significantly associated with receipt of surgery (ARP, 61.9%; CCCP, 45.6%; CCP, 29.9%; INCP, 55.5%; P < 0.001), both for patients with very early tumors ≤2 cm (ARP, 74.7%; CCCP, 66.5%; CCP, 52.4%; INCP, 71.6%; P < 0.001) and for patients with liver metastases (ARP, 21.3%; CCCP, 10.6%; CCP, 5%; INCP, 16.8%; P < 0.001). Treatment at ARPs was associated with improved survival (median overall survival: ARP, 91 mo; CCCP, 47 mo; CCP, 24.5 mo; INCP, 72 mo; P < 0.001).

Conclusions
Treatment of pNETs at academic/research programs is associated with more frequent resections and best survival outcomes. This survival benefit exists for early and late stages and after adjusting for known cofactors.
Cotesting for Human Immunodeficiency Virus and Sexually Transmitted Infections in the Emergency Department
Authors: Seballos Spencer S. , Lopez Rocio , Hustey Fredric M. , Schold Jesse D. , Kadkhoda Kamran , McShane Adam J. , Phelan Michael P. 
Published: May 2022

Background
The Centers for Disease Control and Prevention (CDC) and US Preventive Services Task Force (USPSTF) guidelines recommend screening for human immunodeficiency virus (HIV) in patients aged 15 to 65 years, as well as those at increased risk. Patients screened in the emergency department (ED) for gonorrhea (GC) and/or chlamydia represent an increased-risk population. Our aim was to assess compliance with CDC and USPSTF guidelines for HIV testing in a national sample of EDs.

Methods
We examined data from the 2010 to 2018 Nationwide Emergency Department Sample, which can be used to create national estimates of ED care to query tests for GC, chlamydia, HIV, and syphilis testing. Weighted proportions and 95% confidence intervals (CIs) were reported, and Rao-Scott χ2 tests were used.

Results
We identified 13,443,831 (weighted n = 3,094,214) high-risk encounters in which GC/chlamydia testing was performed. HIV screening was performed in 3.9% (95% CI, 3.4–4.3) of such visits, and syphilis testing was performed in 2.9% (95% CI, 2.7–3.2). Only 1.5% of patients with increased risk encounters received both HIV and syphilis cotesting.

Conclusions
Despite CDC and USPSTF recommendations for HIV and syphilis screening in patients undergoing STI evaluation, only a small proportion of patients are being tested. Further studies exploring the barriers to HIV screening in patients undergoing STI assessment in the ED may help inform future projects aimed at increasing guidance compliance.
Nodular Liver in Portosinusoidal Vascular Disease: A Case of Mistaken Identity
Authors: Alkashash Ahmad M. , Khan Shahbaz , Nephew Lauren , Kubal Chandrashekhar A. , Nelson Nick , Saxena Romil 
Published: May 2022

Background
Portosinusoidal vascular disease (PSVD) has been proposed as a unifying term for vascular abnormalities of the small portal veins and sinusoids that occur in the noncirrhotic liver. This term supersedes other designations including incomplete septal cirrhosis, nodular regenerative hyperplasia, hepatoportal sclerosis, and obliterative portal venopathy. Most patients have noncirrhotic portal hypertension, but the latter is not required to establish a diagnosis of PSVD. Diagnosis requires a liver biopsy of adequate size (≥20 mm long) in the presence of accompanying clinical signs of noncirrhotic portal hypertension and/or histological changes of PSVD. We report a case of severe PSVD that caused severe liver atrophy and required transplantation for intractable hepatic encephalopathy. The explanted liver showed numerous focal nodular hyperplasia-like nodules.

Case Report
A 57-year-old man with neurofibromatosis type 2 and diabetes mellitus type 2 controlled with insulin developed ascites and signs of portal hypertension. He was presumed to have cirrhosis due to nonalcoholic fatty liver disease and underwent liver transplantation for intractable portal hypertension and severe hepatic encephalopathy. The explanted liver had a nodular appearance; however, histological sections showed no bridging fibrosis. Thin, incomplete curvilinear fibrous septa were seen emanating from portal tracts in a patchy distribution. Our case illustrates that PSVD may cause severe hepatic atrophy and lead to architectural abnormalities that may radiologically mimic the parenchymal nodularity of cirrhosis.
Synchronous Mucinous Carcinomas of Ovary and Appendix: A Case Report With Diagnostic Pitfalls and Review of Corresponding Literature
Authors: Hegazy Shaymaa , Bhargava Rohit , Roy Somak , Elishaev Esther 
Published: May 2022

Background
Diagnosis of the primary ovarian mucinous neoplasms occasionally poses a challenge because historically most tumors diagnosed as primary ovarian were documented as metastases from gastrointestinal and pancreatobiliary tracts. This challenge is attributed to the overlapping histologic features, the gray zone, between primary and metastatic mucinous neoplasms in the ovary. While presentation of both primary and metastatic mucinous tumors manifests by the presence of an ovarian mass, determination of the site of origin is clinically significant, because most treatment guidelines are based on the tissue of origin.

Case Presentation
We present an unusual case of mucinous adenocarcinoma of the ovary and the appendix with diagnostic pitfalls and challenges of immunohistochemical profile.

Conclusion
Utilization of molecular analysis in challenging cases of ovarian neoplasms helps to narrow down the gray zone and lessens the misdiagnosis of primary ovarian mucinous tumors.
Sarcomatoid Mesothelioma With Bland Histologic Features: A Potential Pitfall in Diagnosis
Authors: Burke Allen , Hardy Naomi , Fanaroff Rachel , Legesse Teklu 
Published: May 2022

Abstract
Sarcomatoid mesotheliomas can be challenging to diagnose on small biopsy specimens, where limited material may preclude definitive assessment of invasion, and lesional cells can have relatively bland cytology with no mesothelial marker expression. We report a case of a patient who presented with a pleural effusion and had subsequent pleural biopsy that showed a bland, uniform spindle cell proliferation in a mildly myxoid background. There was little, if any, collagen and no chest wall, soft tissue, or fat, and mesothelial markers were negative. The cells were positive for pancytokeratin and GATA3 by immunohistochemistry, and in situ hybridization showed a “negative” result for homozygous loss of CDKN2A; however, there was partial (heterozygous) loss of 1 allele. A diagnosis of atypical spindle cell proliferation was made based on these findings. Several months later, the patient had a repeat pleural biopsy that showed spindled cells with more pleomorphism, areas of invasion into the chest wall, and the same partial loss of CDKN2A, consistent with a sarcomatoid mesothelioma. This case underscores the challenges present on small biopsy specimens and the fact that sarcomatoid mesotheliomas can be relatively bland-appearing with focal pleomorphism and that heterozygous loss of CDKN2A should be considered a positive result indicative of a neoplastic process.
Impact of Opioid Restriction Legislation on Prescribing Practices for Outpatient Plastic and Reconstructive Surgery
Authors: O’Brien Andrew L. , Krasniak Peter J. , Schroeder Michael J. , Desai Miraj N. , Diaz Adrian , Chetta Matthew D. 
Published: May 2022

Background:
Overprescription of opioids for acute postoperative pain, plastic surgery procedures included, is contributing to the pervasive opioid epidemic in the United States. This study examines the effect of a statewide legislation limiting postoperative opioids on opioid prescription behavior among providers following outpatient plastic surgery procedures at a high-volume academic center.

Methods:
Retrospective review of all outpatient surgical encounters between June 1, 2016, and November 30, 2018, was performed. Encounters were grouped into two cohorts: prepolicy and postpolicy. Primary outcomes included total oral morphine equivalents prescribed on the day of surgery and proportion of patients prescribed greater than 210 oral morphine equivalents. Secondary outcomes included proportion of patients requiring an opioid refill within 30 days following surgery, and number of refills required.

Results:
The mean oral morphine equivalents prescribed on the day of surgery was reduced from 271.8 to 150.37 oral morphine equivalents (p < 0.001) following implementation of the legislation, with an associated decrease in the standard deviation of oral morphine equivalents prescribed from 225.35 to 196.71 (p < 0.001), suggesting a decrease in the variability of prescriber practices. Time series analysis demonstrated the decrease in oral morphine equivalents remained significant when accounting for baseline level of change in opioid prescription patterns.

Conclusion:
This study provides evidence that legislation at the state level restricting postoperative opioid prescriptions is associated with a decrease in opioid prescriptions without an increase in the need for refills in the acute postoperative setting following outpatient plastic surgery procedures.
Risks and challenges in COVID-19 infection prevention and control in a hospital setting: perspectives of healthcare workers in Thailand
Authors: Jongdeepaisal Monnaphat , Chunekamrai Puri , Maude Rapeephan R , Maude Richard J 
Published: May 2022

AbstractIn hospital settings, awareness of, and responsiveness to, COVID-19 are crucial to reducing the risk of transmission among healthcare workers (HCWs) and protecting them from infection. Healthcare professionals can offer insights into the practicalities of infection prevention and control measures and on how the protective equipment and training could best be delivered during the pandemic. This study aimed to inform the development of future recommendations to optimise compliance with appropriate use of these measures, and to improve the guidance to reduce their risk of the disease. Drawing on in-depth interviews with HCWs in a hospital in Thailand, several factors influence the use of multiple prevention measures: concerns about infection, availability of the equipment supply, barriers to work performance, and physical limitations in the hospital setting. Setting a ventilated outdoor space for screening and testing, and interaction through mobile technology, were perceived to reduce the transmission risk for staff and patients. Adequate training, clear guidelines, streamlined communications, and management support are crucial to encourage appropriate use of, and adherence to, implementation of infection prevention and control (IPC) measures among HCW. Further study should explore the perceptions and experience of health professionals in local health facilities and community-based workers during the pandemic, particularly in resource-limited settings.
Seasonal movement of royal chambers: where are the kings and queens of temperate termites in winter?
Authors: Takata Mamoru , Konishi Takao , Nagai Shuya , Nozaki Tomonari , Tasaki Eisuke , Matsuura Kenji 
Published: May 2022

AbstractOverwintering is a critical part of the annual cycle for species that live in temperate, polar, and alpine regions. As a result, low-temperature biology is a key determinant of temperate species distribution. Termites distribute predominantly in tropical regions, and only a few species are found in the temperate zone. As with other social insects, termites are characterized by the division of labor between reproductive and non-reproductive castes in which the survival of reproductives is crucial to maintaining their society. Here, in the termiteReticulitermes speratus, we report the discovery of an underground royal chamber that kings and queens use to survive the winter, which is separate from the one they use during the warmer breeding season. Our investigation of field colonies indicates that in the spring the royals are localized in decayed logs on the ground, then move to their underground royal chamber located in the roots of stumps in the fall. The winter minimum temperature measured in the royal chamber was higher than the ground surface temperature. In overwintering termites, the kings and queens had higher cold tolerance than workers and soldiers. The kings and queens were at risk of mortality from −8 °C, compared to the workers and soldiers at −4 °C. Air temperatures dropped below this critical temperature of −8 °C multiple times, as evidenced from the past 140 years of weather records in Kyoto. This suggests that the underground movement of the royal chamber may contribute to avoiding the risk of overwintering mortality. These results demonstrate the social strategies implemented to overcome the environment met while living at the latitudinal limits. This study sheds light on one of the most important aspects of the biology of termites in terms of predicting their geographic distribution and spread by climate change. This work also helps further the understanding of the termite’s social system, seasonal phenology, long-term survivorship, and life cycle, and contributes to the development of pest control strategies.
DrugRepo: A novel approach to repurpose a huge collection of compounds based on chemical and genomic features
Authors: Wang Yinyin , Aldahdooh Jehad , Hu Yingying , Yang Hongbin , Vähä-Koskela Markus , Tang Jing , Tanoli Ziaurrehman 
Published: May 2022

ABSTRACTThe drug development process consumes 9-12 years and approximately one billion US dollars in terms of costs. Due to high finances and time costs required by the traditional drug discovery paradigm, repurposing the old drugs to treat cancer and rare diseases is becoming popular. Computational approaches are mainly data-driven and involve a systematic analysis of different data types leading to the formulation of repurposing hypotheses. This study presents a novel scoring algorithm based on chemical and genomic data types to repurpose vast collection of compounds for 674 cancer types and other diseases. The data types used to design the scoring algorithm are chemical structures, drug-target interactions (DTI), pathways, and disease-gene associations. The repurpose scoring algorithm is strengthened by integrating the most comprehensive manually curated datasets for each data type. More than 100 of our repurposed compounds can be matched with ongoing studies at clinical trials (https://clinicaltrials.gov/). Our analysis is supported by a web tool available at: http://drugrepo.org/.
Detecting intragenic trans-splicing events with hybrid transcriptome sequencing in cancer cells
Authors: Chen Yu-Chen , Chen Chia-Ying , Chiang Tai-Wei , Chan Ming-Hsien , Hsiao Michael , Ke Huei-Mien , Tsai Isheng Jason , Chuang Trees-Juen 
Published: May 2022

AbstractTrans-splicing can generate non-co-linear (NCL) transcripts that consist of exons in an order topologically inconsistent with the corresponding DNA template. Detecting trans-spliced RNAs (ts-RNAs) may be interfered by false positives from experimental artifacts, circular RNAs (circRNAs), and genetic rearrangements. Particularly, intragenic ts-RNAs, which are derived from separate precursor mRNA molecules of the same genes, are often mistaken for circRNAs through analyses of high-throughput transcriptome sequencing (RNA-seq) data. In addition, the biogenesis and function of ts-RNAs remain elusive. Here we developed a bioinformatics pipeline, NCLscan-hybrid, with the integration of long and short RNA-seq reads to minimize false positives and identify intragenic ts-RNAs. We utilized two features of long reads, out-of-circle and rolling circle, to distinguish intragenic ts-RNAs from circRNAs. We also designed multiple experimental validation steps to examine each type of false positives and successfully confirmed an intragenic ts-RNA (ts-ARFGEF1) in breast cancer cells. On the basis of ectopic expression and CRISPR-based endogenous genome modification experiments, we confirmed that ts-ARFGEF1 formation was significantly dependent on the reverse complementary sequences in the flanking introns of the NCL junction. Subsequent in vitro and in vivo experiments demonstrated that ts-ARFGEF1 silencing can significantly inhibit tumor cell growth. We further showed the regulatory role of ts-ARFGEF1 in p53-mediated apoptosis through affecting the PERK/eIF2a/ATF4/CHOP signaling pathway in breast cancer cells. This study thus described both bioinformatics procedures and experimental validation steps for rigorous characterization of transcriptionally non-co-linear RNAs, expanding the discovery of this important but understudied class of RNAs.
A platform for efficient establishment, expansion and drug response profiling of high-grade serous ovarian cancer organoids
Authors: Senkowski Wojciech , Gall-Mas Laura , Falco Matias Marin , Li Yilin , Lavikka Kari , Kriegbaum Mette C. , Oikkonen Jaana , Bulanova Daria , Pietras Elin J. , Voßgröne Karolin , Chen Yan-Jun , Erkan Erdogan Pekcan , Høg Mia Kristine Grønning , Larsen Ida Marie , Lamminen Tarja , Kaipio Katja , Huvila Jutta , Virtanen Anni , Engelholm Lars , Christiansen Pernille , Santoni-Rugiu Eric , Huhtinen Kaisa , Carpén Olli , Hynninen Johanna , Hautaniemi Sampsa , Vähärautio Anna , Wennerberg Krister 
Published: May 2022

AbstractThe broad research use of organoids from high-grade serous ovarian carcinoma (HGSC) has been hampered by low culture success rates and limited availability of fresh tumor material. Here we describe a method for generation and long-term expansion of HGSC organoids with efficacy markedly improved over previous reports (55% vs. 23-38%). We established organoids from cryopreserved material, demonstrating the feasibility of using viably biobanked tissue for HGSC organoid derivation. Genomic, histologic and single-cell transcriptomic analyses revealed that organoids recapitulated genetic and phenotypic features of original tumors. Organoid drug responses correlated with clinical treatment outcomes, although in culture conditions-dependent manner and only in organoids maintained in human plasma-like medium (HPLM). Organoids from consenting patients are available to the research community through a public biobank and organoid genomic data explorable through an interactive online tool. Taken together, this resource facilitates the application of HGSC organoids in basic and translational ovarian cancer research.
Latent dynamics of primary sensory cortical population activity is structured by fluctuations in the local field potential
Authors: Sederberg Audrey , Pala Aurélie , Stanley Garrett B 
Published: May 2022

AbstractAs emerging technologies enable measurement of precise details of the activity within microcircuits at ever-increasing scales, there is a growing need to identify the salient features and patterns within the neural populations that represent physiologically and behaviorally relevant aspects of the network. Accumulating evidence from recordings of large neural populations suggests that neural population activity frequently exhibits relatively low-dimensional structure, with a small number of variables explaining a substantial fraction of the structure of the activity. While such structure has been observed across the brain, it is not known how reduced-dimension representations of neural population activity relate to classical metrics of “brain state,” typically described in terms of fluctuations in the local field potential (LFP), single-cell activity, and behavioral metrics. Here, we relate the latent dynamics of spiking activity of populations of neurons in the whisker area of primary somatosensory cortex of awake mice to classic measurements of cortical state in S1. We found that a hidden Markov model fit the population spiking data well with a relatively small number of states, and that putative inhibitory neurons played an outsize role in determining the latent state dynamics. Spiking states inferred from the model were more informative of the cortical state than a direct readout of the spiking activity of single neurons or of the population. Further, the spiking states predicted both the trial-by-trial variability in sensory responses and one aspect of behavior, whisking activity. Our results show how classical measurements of brain state relate to neural population spiking dynamics at the scale of the microcircuit and provide an approach for quantitative mapping of brain state dynamics across brain areas.Author SummaryBrain states have long been known to strongly shape sensory perception, decision making, cognition, and movement. Brain state during wakefulness changes constantly, classically assessed using changes in the spectral features of the local field potential (LFP) and behavioral measures. However, the connection between these classical measurements of brain state and the collective dynamics of populations of neurons is unclear. Here we fit a latent-variable model to population spiking activity, finding that latent variables inferred under the model are highly predictive of cortical state changes and that the latent dynamics are profoundly shaped by inhibitory cell activity. Our approach connects the activity patterns of ensembles of neurons to a classical measurement of brain state and opens new avenues for investigating brain state dynamics across diverse cortical areas.
Modelling eNvironment for Isoforms (MoNvIso): A general platform to predict structural determinants of protein isoforms in genetic diseases
Authors: Oliva Francesco , Musiani Francesco , Giorgetti Alejandro , De Rubeis Silvia , Sorokina Oksana , Armstrong J. Douglas , Carloni Paolo , Ruggerone Paolo 
Published: May 2022

AbstractThe seamless integration of human disease-related mutation data into protein structures is an essential component of any attempt to correctly assess the impact of the mutation. The key step preliminary to any structural modelling is the identification of the correct isoform onto which mutations should be mapped because there are several functionally different protein isoforms from the same gene. To handle large sets of data coming from omics techniques, this challenging task should be automatized. Here we present our code MoNvIso (Modelling eNvironment for Isoforms), which pinpoints the correct isoform associated with the mutation of interest and builds a structural model of both the wild type isoform and the related variants starting from the name of the gene and the list of mutations of interest.