bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Cell Vulvitis: A Case Series and Follow-Up Study
Authors: Nguyen Jennifer , Veysey Emma 
Published: February 2023

Objectives
Plasma cell vulvitis (PCV) is a rare inflammatory vulvar condition. The aim of this study was to describe the natural history, treatment, impact on quality of life, and factors associated with poorer outcomes for PCV.

Methods
A mixed-methods approach was used combining a retrospective case note review with a cross-sectional telephone questionnaire. All women diagnosed with PCV attending the vulvar disorders clinic at the Royal Women's Hospital between January 2011 and December 2020 were included.

Results
During the 10-year study period, 7,500 women were seen at the vulval disorders clinic, of whom 21 were diagnosed with PCV (0.28%). Of these women, 12 who were followed up for more than 12 months agreed to participate in the study. At a median of 5 years follow-up, there was variability in symptom severity, with more than half of the women still symptomatic with pain, precipitated by friction and dyspareunia, resulting in a moderate to large impact on quality of life. There were 5 women who were asymptomatic. Only 1 woman had a preexisting history of lichen planus and lichen sclerosus. Potent topical corticosteroids were identified as the preferred treatment.

Conclusions
Women with PCV can remain symptomatic for many years with significant impacts on quality of life, which may consequently require long-term support and follow-up.
Vulvar High-Grade Squamous Intraepithelial Lesion and the Risk of Recurrence and Progression to Cancer
Authors: Xavier Joana , Figueiredo Rita , Vieira-Baptista Pedro 
Published: February 2023

Objective
This study aimed to analyze which clinical characteristics are associated with recurrence and progression of vulvar high-grade squamous intraepithelial lesion (vHSIL).

Materials and Methods
This was a retrospective cohort study, including all women with vHSIL followed in 1 center between 2009 and 2021. Women with a concomitant diagnosis of invasive vulvar cancer were excluded. Medical records were reviewed for demographic factors, clinical data, treatment type, histopathologic results, and follow-up information.

Results
A total of 30 women were diagnosed with vHSIL. The median follow-up time was 4 years (range = 1–12 years). More than half of the women (56.7% [17/30]) underwent excisional treatment, whereas 26.7% (8/30) underwent combined (excisional plus medical) treatment, and 16.7% (5/30) only had medical treatment (imiquimod). Six women had recurrence of vHSIL (20% [6/30]), with a mean time to recurrence of 4.7 ± 2.88 years. The progression rate to invasive vulvar cancer was 13.3% (4/30), with a mean time to progression of 1.8 ± 0.96 years. Multifocal disease was associated with progression to vulvar cancer (p = .035). We did not identify other variables associated with progression; no differences were found between women with and without recurrences.

Conclusions
Multifocality of the lesions was the only variable associated with progression to vulvar cancer. This reinforces the idea that these lesions are a challenge in both treatment and surveillance, involving a more difficult therapeutic decision with greater associated morbidity.
The epigenetic legacy of ICU feeding and its consequences
Authors: Vanhorebeek Ilse , Van den Berghe Greet 
Published: February 2023

Purpose of review
Many critically ill patients face physical, mental or neurocognitive impairments up to years later, the etiology remaining largely unexplained. Aberrant epigenetic changes have been linked to abnormal development and diseases resulting from adverse environmental exposures like major stress or inadequate nutrition. Theoretically, severe stress and artificial nutritional management of critical illness thus could induce epigenetic changes explaining long-term problems. We review supporting evidence.

Recent findings
Epigenetic abnormalities are found in various critical illness types, affecting DNA-methylation, histone-modification and noncoding RNAs. They at least partly arise de novo after ICU-admission. Many affect genes with functions relevant for and several associate with long-term impairments. As such, de novo DNA-methylation changes in critically ill children statistically explained part of their disturbed long-term physical/neurocognitive development. These methylation changes were in part evoked by early-parenteral-nutrition (early-PN) and statistically explained harm by early-PN on long-term neurocognitive development. Finally, long-term epigenetic abnormalities beyond hospital-discharge have been identified, affecting pathways highly relevant for long-term outcomes.

Summary
Epigenetic abnormalities induced by critical illness or its nutritional management provide a plausible molecular basis for their adverse effects on long-term outcomes. Identifying treatments to further attenuate these abnormalities opens perspectives to reduce the debilitating legacy of critical illness.
The Effects of Adipose-Derived Mesenchymal Stem Cells and Adipose-Derived Mesenchymal Stem Cell–Originating Exosomes on Nerve Allograft Regeneration
Authors: Koplay Tugba Gun , Yildiran Gokce , Dursunoglu Duygu , Aktan Murad , Duman Selcuk , Akdag Osman , Karamese Mehtap , Tosun Zekeriya 
Published: February 2023

Introduction
Nerve regeneration has been the subject of many studies because of its complex mechanism and functional outcome. Mesenchymal stem cells and exosomes are promising factors in regeneration in many areas. Reconstruction of nerve defects is a controversial issue, and nerve allografts are promising alternatives with many advantages. In this study, it is aimed to evaluate the nerve regeneration in cellularized and decellularized nerve allografts and whether it is possible to accelerate this process with adipose-derived mesenchymal stem cells (ad MSC) or ad MSC–originating exosomes.

Method
This study was performed with 36 Lewis and 18 Brown Norway isogenic male rats aged 10 to 12 weeks and weighing 300 to 350 g. The Lewis rats were divided into 6 groups. Nerve allografts at a length of 12 mm that were obtained from the Brown Norway rats' proximal portion of both sciatic nerve branching points were coapted as cellularized in group A and decellularized in group B to the sciatic nerve defects of the Lewis rats. Group A received oral tacrolimus (0.2 mg/kg) for 30 days. Perineural saline (A1-B1), ad MSC (A2-B2), or ad MSC–originating exosomes (A3-B3) were applied to these groups. Walking track analysis, pinch-prick test and electromyelography were applied at the 8th and 16th weeks following surgery. Nerves were examined histopathologically at the 16th week.

Results
Between cellularized groups, better results were shown in A3 about axon-myelin regeneration/organization (P = 0.001), endoneural connective tissue (P = 0.005), and inflammation (P = 0.004). Better results were shown in the B2 and B3 groups electromyelographicaly about latency period (P = 0.033) and action potential (P = 0.008) at late period, and histomorphologicaly at vascularization (P = 0.012).

Discussion
It is argued that regeneration is accelerated with decellularization of nerve allografts by removing the chondroidin sulfate proteoglycans. The positive effects of stem cells are derived by exosomes without the cell-related disadvantages. In this study, better results were obtained by decellularization and perineural application of ad MSC and/or ad MSC exosome.
Timing of Unplanned Reoperation After Lower Extremity Free Flap Reconstruction
Authors: Elmer Nicholas A. , Araya Sthefano , Panichella Juliet , Egleston Brian , Deng Mengying , Patel Sameer A. 
Published: February 2023

Background
Advancements in lower extremity (LE) microsurgery have allowed for the expansion of indications for LE reconstructions. This project aims to better understand the temporal pattern and risk factors associated with LE free flap failure based on the clinical indication.

Materials and Methods
We analyzed all patients undergoing LE free flap reconstruction from the American College of Surgeons National Surgical Quality Improvement Program 2012–2019 prospectively collected data to determine rates and timing of reoperation. Free flaps were stratified by indication, type, and timing of reoperation. Weibull survival models were used to compare rates of takebacks among time intervals. Multivariable logistic regression was used to identify independent predictors for unplanned reoperation.

Results
Four hundred seven of LE free flaps were analyzed. There was a 14.5% rate (59/407) of unplanned reoperation within the first 30 postoperative days (PODs) after surgery. When stratified by the indication necessitating reoperation, patients with an underlying vascular indication had the highest rate of reoperation (40.9%). The reoperation rates were significantly different between indications (P < 0.05) The mean daily proportion of patients experiencing reoperation was highest during POD 0 to 2 (1.47% reoperations per day), which dropped significantly during POD 3 to 10 (0.55% per day) and again during POD 11 to 30 (0.28% per day, P < 0.05). African American race as well as malignant, prosthetic/implant, and wound/infectious indications were significant independent predictors for unplanned reoperation.

Conclusions
Lower extremity reconstruction is an important reconstructive option for the coverage of a myriad of defects. Understanding the differences between postoperative reoperation timelines among indication subtypes is important for updated flap monitoring protocols, optimizing ERAS pathways, and beginning dangle protocols.
Ram pressure in astronomy and engineering
Authors: Dowling Timothy E. , Bradley Mary E. 
Published: February 2023

The ram pressure of a moving fluid,

P
r

, is the rise in pressure at a stagnation point relative to the upstream pressure. In astronomy, it is used to calculate the interaction of stellar winds with planets and to quantify the effects of ram pressure stripping. On aeroplanes and in wind tunnels, it is measured with a pitot-static tube, an inexpensive device with no moving parts that was invented in 1732. Up through the mid-1960s, across both astronomy and engineering the ram pressure of a moving gas and its momentum flux,

ρ

u
2

, where

ρ

and

u

are the upstream mass density and flow speed, were properly treated as related but distinct quantities. This relationship may be expressed as

P
r

=

Sp

ρ

u
2

, where

Sp

is the dimensionless Spreiter number, which ranges between 0.5 and 0.88 for a monatomic gas, depending on the upstream Mach number,

Ma

. Unfortunately, by the early 1970s, in astronomy ram pressure was
defined
to be the momentum flux and

Sp

was fixed to be unity and forgotten as a parameter. This article seeks to raise awareness of this issue, and to review the determination of

Sp

for subsonic and supersonic flow.
Characterizing the use of the ICD-10 Code for Long COVID in 3 US Healthcare Systems
Authors: Zhang Harrison G , Honerlaw Jacqueline P , Maripuri Monika , Samayamuthu Malarkodi Jebathilagam , Beaulieu-Jones Brendin R , Baig Huma S , L’Yi Sehi , Ho Yuk-Lam , Morris Michele , Panickan Vidul Ayakulangara , Wang Xuan , Hong Chuan , Weber Griffin M , Liao Katherine P , Visweswaran Shyam , Tan Bryce W.Q. , Yuan William , Gehlenborg Nils , Muralidhar Sumitra , Ramoni Rachel B ,   The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), Kohane Isaac S , Xia Zongqi , Cho Kelly , Cai Tianxi , Brat Gabriel A 
Published: February 2023

ABSTRACTThe International Classification of Diseases (ICD)-10 code (U09.9) for post-acute sequelae of COVID-19 (PASC) was introduced in October of 2021. As researchers seek to leverage this billing code for research purposes in large scale real-world studies of PASC, it is of utmost importance to understand the functional use of the code by healthcare providers and the clinical characteristics of patients who have been assigned this code. To this end, we operationalized clinical case definitions of PASC using World Health Organization and Centers for Disease Control guidelines. We then chart reviewed 300 patients with COVID-19 from three participating healthcare systems of the 4CE Consortium who were assigned the U09.9 code. Chart review results showed the average positive predictive value (PPV) of the U09.9 code ranged from 40.2% to 65.4% depending on which definition of PASC was used in the evaluation. The PPV of the U09.9 code also fluctuated significantly between calendar time periods. We demonstrated the potential utility of textual data extracted from natural language processing techniques to more comprehensively capture symptoms associated with PASC from electronic health records data. Finally, we investigated the utilization of long COVID clinics in the cohort of patients. We observed that only an average of 24.0% of patients with the U09.9 code visited a long COVID clinic. Among patients who met the WHO PASC definition, only an average of 35.6% visited a long COVID clinic.
Early Treatment, Inflammation and Post-COVID Conditions
Authors: Gebo Kelly A. , Heath Sonya L. , Fukuta Yuriko , Zhu Xianming , Baksh Sheriza , Abraham Alison G. , Habtehyimer Feben , Shade David , Ruff Jessica , Ram Malathi , Laeyendecker Oliver , Fernandez Reinaldo E. , Patel Eshan U. , Baker Owen R. , Shoham Shmuel , Cachay Edward R. , Currier Judith S. , Gerber Jonathan M. , Meisenberg Barry , Forthal Donald N. , Hammitt Laura L. , Huaman Moises A. , Levine Adam , Mosnaim Giselle S. , Patel Bela , Paxton James H. , Raval Jay S. , Sutcliffe Catherine G. , Anjan Shweta , Gniadek Thomas , Kassaye Seble , Blair Janis E. , Lane Karen , McBee Nichol A. , Gawad Amy L. , Das Piyali , Klein Sabra L. , Pekosz Andrew , Casadevall Arturo , Bloch Evan M. , Hanley Daniel , Tobian Aaron A.R. , Sullivan David J. 
Published: February 2023

ABSTRACTBackgroundPost-COVID conditions (PCC) are common and have significant morbidity. Risk factors for PCC include advancing age, female sex, obesity, and diabetes mellitus. Little is known about early treatment, inflammation, and PCC.MethodsAmong 883 individuals with confirmed SARS-CoV-2 infection participating in a randomized trial of CCP vs. control plasma with available biospecimens and symptom data, the association between early COVID treatment, cytokine levels and PCC was evaluated. Cytokine and chemokine levels were assessed at baseline, day 14 and day 90 using a multiplexed sandwich immuosassay (Mesoscale Discovery). Presence of any self-reported PCC symptoms was assessed at day 90. Associations between COVID treatment, cytokine levels and PCC were examined using multivariate logistic regression models.ResultsOne-third of the 882 participants had day 90 PCC symptoms, with fatigue (14.5%) and loss of smell (14.5%) being most common. Cytokine levels decreased from baseline to day 90. In a multivariable analysis including diabetes, body mass index, race, and vaccine status, female sex (adjusted odds ratio[AOR]=2.70[1.93-3.81]), older age (AOR=1.32[1.17-1.50]), and elevated baseline levels of IL-6 (AOR=1.59[1.02-2.47]) were associated with development of PCC. There was a trend for decreased PCC in those with early CCP treatment (<5 days after symptom onset) compared to late CCP treatment.ConclusionIncreased IL-6 levels were associated with the development of PCC and there was a trend for decreased PCC with early CCP treatment in this predominately unvaccinated population. Future treatment studies should evaluate the effect of early treatment and anti-IL-6 therapies on PCC development.SummaryIncreased IL-6 levels were associated with the development of Post-COVID Conditions (PCC) and there was a trend for decreased PCC with early COVID convalescent plasma treatment in this predominately unvaccinated population.
Pancreatic cancer symptom trajectories from Danish registry data and free text in electronic health records
Authors: Hjaltelin Jessica Xin , Novitski Sif Ingibergsdóttir , Jørgensen Isabella Friis , Johansen Julia Sidenius , Chen Inna M , Siggaard Troels , Vulpius Siri , Jensen Lars Juhl , Brunak Søren 
Published: February 2023

AbstractPancreatic cancer is one of the deadliest cancer types with poor treatment options. Better detection of early symptoms and relevant disease correlations could improve pancreatic cancer prognosis. In this retrospective study, we used symptom and disease codes (ICD-10) from the Danish National Patient Registry (NPR) encompassing 8.1 million patients from 1977 to 2018, of whom 22,727 were diagnosed with pancreatic cancer. To complement and compare these diagnosis codes with deeper clinical data, we used a text mining approach to extract symptoms from free text clinical notes in electronic health records (4,418 pancreatic cancer patients and 44,180 controls). We used both data sources to generate and compare symptom disease trajectories to uncover temporal patterns of symptoms prior to pancreatic cancer diagnosis for the same patients. We show that the text mining of the clinical notes was able to capture richer statistically significant symptom patterns, in particular general pain, abdominal pain, and liver-related conditions. We also detected haemorrhages (p-value =4.80·10-08) and headache (p-value =2.12·10-06) to be linked as early symptoms of pancreatic cancer. Chaining symptoms together in trajectories identified patients with jaundice conditions having higher median survival (>90 days) compared to patients following trajectories that included haemorrhage, oedema or anaemia (≤90 days). Additionally, we discovered a group of cardiovascular patients that developed pancreatic cancer with a lower median survival (≤90 days). These results provide an overview of two types of pancreatic cancer symptom trajectories. The two approaches and data types complement each other to provide a fuller picture of the early risk factors for pancreatic cancer.
Spatial transcriptomic analysis of Sonic Hedgehog Medulloblastoma identifies that the loss of heterogeneity and promotion of differentiation underlies the response to CDK4/6 inhibition
Authors: Vo Tuan , Balderson Brad , Jones Kahli , Ni Guiyan , Crawford Joanna , Millar Amanda , Tolson Elissa , Singleton Matthew , Mulay Onkar , Walters Shaun , Kojic Marija , Robertson Thomas , Bhuva Dharmesh D. , Davis Melissa J. , Wainwright Brandon J. , Nguyen Quan , Genovesi Laura A. 
Published: February 2023

AbstractBackgroundMedulloblastoma (MB) is a malignant tumour of the cerebellum which can be classified into four major subgroups based on gene expression and genomic features. Single cell transcriptome studies have defined the cellular states underlying each MB subgroup, however the spatial organisation of these diverse cell states and how this impacts response to therapy remains to be determined.MethodsHere, we used spatially resolved transcriptomics to define the cellular diversity within a sonic hedgehog (SHH) patient-derived model of MB and identify how cells specific to a transcriptional state or spatial location are pivotal in responses to treatment with the CDK4/6 inhibitor, Palbociclib. We integrated spatial gene expression with histological annotation and single cell gene expression data from MB, developing a analysis strategy to spatially map cell type responses within the hybrid system of human and mouse cells and their interface within an intact brain tumour section.ResultsWe distinguish neoplastic and non-neoplastic cells within tumours and from the surrounding cerebellar tissue, further refining pathological annotation. We identify a regional response to Palbociclib, with reduced proliferation and induced neuronal differentiation in both treated tumours. Additionally, we resolve at a cellular resolution a distinct tumour interface where the tumour contacts neighbouring mouse brain tissue consisting of abundant astrocytes and microglia and continues to proliferate despite Palbociclib treatment.ConclusionsOur data highlight the power of using spatial transcriptomics to characterise the response of a tumour to a targeted therapy and provide further insights into the molecular and cellular basis underlying the response and resistance to CDK4/6 inhibitors in SHH MB.
A novel triptolide analog downregulates NF-κB and induces mitochondrial apoptosis pathways in human pancreatic cancer
Authors: Tian Qiaomu , Zhang Peng , Wang Yihan , Si Youhui , Yin Dengping , Weber Christopher R , Fishel Melissa L , Pollok Karen E , Qiu Bo , Xiao Fei , Chong Anita S 
Published: February 2023

AbstractBackgroundPancreatic cancer is the seventh leading cause of cancer-related death worldwide, and despite advancements in disease management, the 5-year survival rates stands at only 9%. Triptolides have potent anti-tumor activity against different types of cancers, including pancreatic cancer, however poor solubility and toxicity limit their translation into clinical use.MethodsWe synthesized a novel pro-drug of triptolide, (E)-19-[(1’-benzoyloxy-1’-phenyl)-methylidene]-Triptolide (CK21), and formulated into an emulsion for in vitro and in vivo testing in rats and mice, and using human pancreatic cancer cell lines and patient-derived pancreatic tumor organoids. A time-course transcriptomic profiling of tumor organoids treated with CK21 in vitro was conducted to define its mechanism of action, as well as transcriptomic profiling at a single time point post-CK21 administration in vivo.FindingsIntravenous administration of emulsified CK21 resulted in the stable release of triptolide, and potent anti-proliferative effects on human pancreatic cancer cell lines and patient-derived pancreatic tumor organoidsin vitro,and with minimal toxicityin vivo. Time course transcriptomic profiling of tumor organoids treated with CK21in vitrorevealed <10 differentially expressed genes (DEGs) at 3 h and ∼8,000 DEGs at 12 h. Overall inhibition of general RNA transcription was observed, and Ingenuity pathway analysis together with functional cellular assays confirmed inhibition of the NF-κB pathway, increased oxidative phosphorylation and mitochondrial dysfunction, leading ultimately to increased reactive oxygen species (ROS) production, reduced B-cell-lymphoma protein 2 (BCL2) expression, and mitochondrial-mediated tumor cell apoptosis.InterpretationCK21 is a novel pro-drug of triptolide that exerts potent anti-proliferative effects on human pancreatic tumors by inhibiting the NF-κB pathway, leading ultimately to mitochondrial-mediated tumor cell apoptosis.FundingThe study of the anti-tumor efficacy of CK21 supported in part by a research grant from Cinkate Pharmaceutical Corp; the funders had no role in the study design, interpretation or decision to publish. Patient-derived pancreatic tumor organoids were a generous gift from the Organoid and Primary Culture Research Core at University of Chicago.