bluuebunny/crossref_metadata_2025 huggingface dataset:
Pulmonary metastasectomy and repeat metastasectomy for colorectal pulmonary metastases: outcomes from the Dutch Lung Cancer Audit for Surgery
Authors: van Dorp Martijn , Wolfhagen Nienke , Torensma Bart , Dickhoff Chris , Kazemier Geert , Heineman David J , Schreurs Wilhelmina H
Published: May 2023

Background

Surgical resection of recurrent pulmonary metastases in patients with colorectal cancer is an established treatment option; however, the evidence for repeat resection is limited. The aim of this study was to analyse long-term outcomes from the Dutch Lung Cancer Audit for Surgery.

Methods

Data from the mandatory Dutch Lung Cancer Audit for Surgery were used to analyse all patients after metastasectomy or repeat metastasectomy for colorectal pulmonary metastases from January 2012 to December 2019 in the Netherlands. Kaplan–Meier survival analysis was performed to determine the difference in survival. Multivariable Cox regression analyses were performed to identify predictors of survival.

Results

A total of 1237 patients met the inclusion criteria, of which 127 patients underwent repeat metastasectomy. Five-year overall survival was 53 per cent after pulmonary metastasectomy for colorectal pulmonary metastases and 52 per cent after repeat metastasectomy (P = 0.852). The median follow-up was 42 (range 0–285) months. More patients experienced postoperative complications after repeat metastasectomy compared with the first metastasectomy (18.1 per cent versus 11.6 per cent respectively; P = 0.033). Eastern Cooperative Oncology Group performance status greater than or equal to 1 (HR 1.33, 95 per cent c.i. 1.08 to 1.65; P = 0.008), multiple metastases (HR 1.30, 95 per cent c.i. 1.01 to 1.67; P = 0.038), and bilateral metastases (HR 1.50, 95 per cent c.i. 1.01 to 2.22; P = 0.045) were prognostic factors on multivariable analysis for pulmonary metastasectomy. Diffusing capacity of the lungs for carbon monoxide less than 80 per cent (HR 1.04, 95 per cent c.i. 1.01 to 1.06; P = 0.004) was the only prognostic factor on multivariable analysis for repeat metastasectomy.

Conclusion

This study demonstrates that patients with colorectal pulmonary metastases have comparable median and 5-year overall survival rates after primary or recurrent pulmonary metastasectomy. However, repeat metastasectomy has a higher risk of postoperative complications.
Aquaporin-4 and GPRC5B: old and new players in controlling brain oedema
Authors: Passchier Emma M J , Kerst Sven , Brouwers Eelke , Hamilton Eline M C , Bisseling Quinty , Bugiani Marianna , Waisfisz Quinten , Kitchen Philip , Unger Lucas , Breur Marjolein , Hoogterp Leoni , de Vries Sharon I , Abbink Truus E M , Kole Maarten H P , Leurs Rob , Vischer Henry F , Brignone Maria S , Ambrosini Elena , Feillet François , Born Alfred P , Epstein Leon G , Mansvelder Huibert D , Min Rogier , van der Knaap Marjo S
Published: May 2023

Brain oedema is a life-threatening complication of various neurological conditions. Understanding molecular mechanisms of brain volume regulation is critical for therapy development. Unique insight comes from monogenic diseases characterized by chronic brain oedema, of which megalencephalic leukoencephalopathy with subcortical cysts (MLC) is the prototype. Variants in MLC1 or GLIALCAM, encoding proteins involved in astrocyte volume regulation, are the main causes of MLC. In some patients, the genetic cause remains unknown.

We performed genetic studies to identify novel gene variants in MLC patients, diagnosed by clinical and MRI features, without MLC1 or GLIALCAM variants. We determined subcellular localization of the related novel proteins in cells and in human brain tissue. We investigated functional consequences of the newly identified variants on volume regulation pathways using cell volume measurements, biochemical analysis and electrophysiology.

We identified a novel homozygous variant in AQP4, encoding the water channel aquaporin-4, in two siblings, and two de novo heterozygous variants in GPRC5B, encoding the orphan G protein-coupled receptor GPRC5B, in three unrelated patients. The AQP4 variant disrupts membrane localization and thereby channel function. GPRC5B, like MLC1, GlialCAM and aquaporin-4, is expressed in astrocyte endfeet in human brain. Cell volume regulation is disrupted in GPRC5B patient-derived lymphoblasts. GPRC5B functionally interacts with ion channels involved in astrocyte volume regulation.

In conclusion, we identify aquaporin-4 and GPRC5B as old and new players in genetic brain oedema. Our findings shed light on the protein complex involved in astrocyte volume regulation and identify GPRC5B as novel potentially druggable target for treating brain oedema.
An Error Term in the Central Limit Theorem for Sums of Discrete Random Variables
Authors: Dolgopyat Dmitry , Fernando Kasun
Published: May 2023

We consider sums of independent identically distributed random variables whose distributions have $d+1$ atoms. Such distributions never admit an Edgeworth expansion of order $d$, but we show that for almost all parameters the Edgeworth expansion of order $d-1$ is valid and the error of the order $d-1$ Edgeworth expansion is typically of order $n^{-d/2}.$
Juvenile idiopathic epilepsy in Arabian horses is not a single-gene disorder
Authors: Ciosek Julia , Kimes Abigail , Vinardell Tatiana , Miller Donald C , Antczak Douglas F , Brooks Samantha
Published: May 2023

Valued for their temperament, beauty, athletic ability, and exhibition in the show ring, Arabian horses are an important component of the horse industry. Juvenile idiopathic epilepsy (JIE), a seizure disorder, is most often reported in Arabian foals from birth to 6 months of age. Affected foals exhibit tonic–clonic seizures lasting as long as 5 min and risking secondary complications like temporary blindness and disorientation. Some foals outgrow this condition, while others die or suffer lifelong complications if not treated. Previous work suggested a strong genetic component to JIE and proposed JIE to be a single-gene trait. In this work, we conducted a genome wide association study (GWAS) in 60 cases of JIE and 120 genetically matched controls, identifying loci suggesting JIE is not caused by a single locus. Coat color (chestnut, gray) phenotypes were used as positive control traits to assess the efficacy of GWAS in this population. Future work will attempt to future define candidate regions and explore a polygenic mode of inheritance.
Predicting Environmental and Ecological Drivers of Human Population Structure
Authors: Pless Evlyn , Eckburg Anders M , Henn Brenna M
Published: May 2023

Landscape, climate, and culture can all structure human populations, but few existing methods are designed to simultaneously disentangle among a large number of variables in explaining genetic patterns. We developed a machine learning method for identifying the variables which best explain migration rates, as measured by the coalescent-based program MAPS that uses shared identical by descent tracts to infer spatial migration across a region of interest. We applied our method to 30 human populations in eastern Africa with high-density single nucleotide polymorphism array data. The remarkable diversity of ethnicities, languages, and environments in this region offers a unique opportunity to explore the variables that shape migration and genetic structure. We explored more than 20 spatial variables relating to landscape, climate, and presence of tsetse flies. The full model explained ∼40% of the variance in migration rate over the past 56 generations. Precipitation, minimum temperature of the coldest month, and elevation were the variables with the highest impact. Among the three groups of tsetse flies, the most impactful was fusca which transmits livestock trypanosomiasis. We also tested for adaptation to high elevation among Ethiopian populations. We did not identify well-known genes related to high elevation, but we did find signatures of positive selection related to metabolism and disease. We conclude that the environment has influenced the migration and adaptation of human populations in eastern Africa; the remaining variance in structure is likely due in part to cultural or other factors not captured in our model.
Reduction ofParaoxonaseExpression Followed by Inactivation across Independent Semiaquatic Mammals Suggests Stepwise Path to Pseudogenization
Authors: Graham Allie M , Jamison Jerrica M , Bustos Marisol , Cournoyer Charlotte , Michaels Alexa , Presnell Jason S , Richter Rebecca , Crocker Daniel E , Fustukjian Ari , Hunter Margaret E , Rea Lorrie D , Marsillach Judit , Furlong Clement E , Meyer Wynn K , Clark Nathan L
Published: May 2023

Convergent adaptation to the same environment by multiple lineages frequently involves rapid evolutionary change at the same genes, implicating these genes as important for environmental adaptation. Such adaptive molecular changes may yield either change or loss of protein function; loss of function can eliminate newly deleterious proteins or reduce energy necessary for protein production. We previously found a striking case of recurrent pseudogenization of the Paraoxonase 1 (Pon1) gene among aquatic mammal lineages—Pon1 became a pseudogene with genetic lesions, such as stop codons and frameshifts, at least four times independently in aquatic and semiaquatic mammals. Here, we assess the landscape and pace of pseudogenization by studying Pon1 sequences, expression levels, and enzymatic activity across four aquatic and semiaquatic mammal lineages: pinnipeds, cetaceans, otters, and beavers. We observe in beavers and pinnipeds an unexpected reduction in expression of Pon3, a paralog with similar expression patterns but different substrate preferences. Ultimately, in all lineages with aquatic/semiaquatic members, we find that preceding any coding-level pseudogenization events in Pon1, there is a drastic decrease in expression, followed by relaxed selection, thus allowing accumulation of disrupting mutations. The recurrent loss of Pon1 function in aquatic/semiaquatic lineages is consistent with a benefit to Pon1 functional loss in aquatic environments. Accordingly, we examine diving and dietary traits across pinniped species as potential driving forces of Pon1 functional loss. We find that loss is best associated with diving activity and likely results from changes in selective pressures associated with hypoxia and hypoxia-induced inflammation.
A network of DZF proteins controls alternative splicing regulation and fidelity
Authors: Haque Nazmul , Will Alexander , Cook Atlanta G , Hogg J Robert
Published: May 2023

Proteins containing DZF (domain associated with zinc fingers) modules play important roles throughout gene expression, from transcription to translation. Derived from nucleotidyltransferases but lacking catalytic residues, DZF domains serve as heterodimerization surfaces between DZF protein pairs. Three DZF proteins are widely expressed in mammalian tissues, ILF2, ILF3 and ZFR, which form mutually exclusive ILF2–ILF3 and ILF2–ZFR heterodimers. Using eCLIP-Seq, we find that ZFR binds across broad intronic regions to regulate the alternative splicing of cassette and mutually exclusive exons. ZFR preferentially binds dsRNA in vitro and is enriched on introns containing conserved dsRNA elements in cells. Many splicing events are similarly altered upon depletion of any of the three DZF proteins; however, we also identify independent and opposing roles for ZFR and ILF3 in alternative splicing regulation. Along with widespread involvement in cassette exon splicing, the DZF proteins control the fidelity and regulation of over a dozen highly validated mutually exclusive splicing events. Our findings indicate that the DZF proteins form a complex regulatory network that leverages dsRNA binding by ILF3 and ZFR to modulate splicing regulation and fidelity.
Bernanke and Kindleberger on financial crises, 1978–2003
Authors: Carré Emmanuel , Le Maux Laurent
Published: May 2023

Ben Bernanke and Charles Kindleberger both studied financial crises. One interpretation in monetary macroeconomics associates them over their endorsement of the credit view as opposed to the money view. We suggest another interpretation and compare their contributions on financial crises more closely. This comparison makes all the more sense as the two authors were engaged in a discussion that the literature has not studied in depth, but that forms the Ariadne’s thread of our investigation. We show that the difference did not so much concern the distinction between rationality and irrationality hypothesis, or between policy and market failure, as the distinction between exogeneity and endogeneity of financial crises. Bernanke rested on the assumption of any kind of exogenous shocks and studied their effects on credit intermediation, whereas Kindleberger analysed credit intermediation throughout the financial cycle and pointed out the causes of financial crises as the culmination of the endogenous process.
911 Usage by Boston Public Schools: A Researcher–Practitioner Partnership
Authors: Morabito Melissa S , Green Jennifer Greif , Savage Jenna , Battal Jill , Walker Whitney
Published: May 2023

To reduce police presence in schools, School Resource Officer programmes are being eliminated across the USA. However, police also become involved in schools through other routes—namely, in response to school calls to 911. This type of police involvement has generally been overlooked in prior studies of school use of police services. In addition, prior research has primarily relied on interview and survey data of school administrators. We describe a researcher–practitioner partnership created to address the limitations of this prior research and to answer foundational questions from one urban school district—Boston Public Schools (BPS)—about police involvement in schools through calls to 911. First, we discuss ongoing collaborative work conducted among the Boston Police Department (BPD), BPS, and academic partners. Next, we provide an example of how this partnership can address pressing questions identified by BPS by providing the results of an analysis of 911 calls. In particular, we examine the ways in which elementary versus secondary schools in the BPS system differ in their patterns of 911 usage across schools when requesting assistance from the BPD. This work provides an example of how researcher–practitioner partnerships can inform policy and practice in schools, and guide decision-making about school-based police services.
Association of anti-TPM4 autoantibodies with vasculopathic cutaneous manifestations in juvenile dermatomyositis
Authors: Karasawa Rie , Yudoh Kazuo , Sato Toshiko , Tanaka Megumi , Sabbagh Sara E , Flegel Willy A , Mammen Andrew L , Jarvis James N , Rider Lisa G ,   for the Childhood Myositis Heterogeneity Study Group, Arabshahi Bita , Bingham April , Cartwright Victoria , Curiel Rodolfo , DeGuzman Marietta M , Eberhard Barbara Anne , Edelheit Barbara S , Finkel Terri H , Hannan William , Henrickson Michael , Huber Adam M , Jansen Anna , Klein Steven J , Lang Bianca , Lindsley Carol B , Mamyrova Gulnara , Miller Frederick W , Mitchell Stephen R , Nanda Kabita , Farhadi Payam Noroozi , Passo Murray H , Person Donald A , Ronis Tova , Schiffenbauer Adam , Shaham Bracha , Stoll Matthew L , Sule Sangeeta H , Targoff Ira N , Vogelgesang Scott A , Volochayev Rita , Wargula Jennifer C , Weiss Pamela
Published: May 2023

Objectives

AECAs are detected in multiple forms of vasculitis or vasculopathy, including JDM. High levels of tropomyosin alpha-4 chain (TPM4) gene expression in cutaneous lesions and TPM4 protein expression in some endothelial cells (ECs) have been proven. Furthermore, the presence of autoantibodies to tropomyosin proteins have been discovered in DM. We therefore investigated whether anti-TPM4 autoantibodies are an AECA in JDM and are correlated with clinical features of JDM.

Methods

The expression of TPM4 protein in cultured normal human dermal microvascular ECs was investigated by Western blotting. Plasma samples from 63 children with JDM, 50 children with polyarticular JIA (pJIA) and 40 healthy children (HC) were tested for the presence of anti-TPM4 autoantibodies using an ELISA. Clinical features were compared between JDM patients with and without anti-TPM4 autoantibodies.

Results

Autoantibodies to TPM4 were detected in the plasma of 30% of JDM, 2% of pJIA (P < 0.0001) and 0% of HC (P < 0.0001). In JDM, anti-TPM4 autoantibodies were associated with the presence of cutaneous ulcers (53%; P = 0.02), shawl sign rash (47%; P = 0.03), mucous membrane lesions (84%; P = 0.04) and subcutaneous edema (42%; P < 0.05). Anti-TPM4 autoantibodies significantly correlated with the use of intravenous steroids and IVIG therapy in JDM (both P = 0.01). The total number of medications received was higher in patients with anti-TPM4 autoantibodies (P = 0.02).

Conclusion

Anti-TPM4 autoantibodies are detected frequently in children with JDM and are novel myositis-associated autoantibodies. Their presence correlates with vasculopathic and other cutaneous manifestations of JDM that may be indicative of more refractory disease.
Policy entrepreneurs, entrepreneurial strategies, and institutional contexts in Interreg Europe
Authors: Morisson Arnault , Petridou Evangelia
Published: May 2023

In their efforts to affect policy change, policy entrepreneurs employ a series of strategies, which have been well documented in the literature. However, little is known regarding the relationship between the types of strategies policy entrepreneurs use and the institutional contexts in which they operate. The Interreg Europe programme aims to promote policy changes and thus offers a space for policy learning and experimentation to policy entrepreneurs. Using a mixed methodology that includes a survey addressed to the sixty-five Interreg Europe projects in research and innovation during the programming period 2014–20 and twelve follow-up semi-structured interviews, this article explores the strategies used by policy entrepreneurs in different institutional contexts. The study, rare in the policy entrepreneurship scholarship with its quantitative aspects, highlights the most widely-used strategies by policy entrepreneurs in research and innovation policy changes. Findings suggest that the strategy of storytelling is more widely used in high-innovator regions than in low-innovator regions and in Northern European regions compared to Southern European regions. Moreover, policy entrepreneurs who employ the storytelling strategy find it easier to introduce a policy change.
The influence of the leading-edge angle of subgrade on the aerodynamic loads of a high-speed train in a wind tunnel
Authors: Yang Zeyun , Xu Gang , Wu Fan , Zhang Lei , Du Jian , Vainchtein Dmitri
Published: May 2023

The purpose of this study is to establish the correlation between the boundary layer over the subgrade and the aerodynamic loads acting on the train model in conventional wind tunnel tests. Firstly, flow characteristics around the subgrade with different leading-edge angles (15°, 30° and 45°) are investigated through the particle image velocimetry (PIV) experimental test method. Then, wind tunnel tests of the aerodynamic performance of a high-speed train are carried out. The results are compared with previous experimental data obtained by moving model tests. Results show that, due to the presence of a boundary layer, the pressure acting on the lower part of the train head decreases, while other locations are not significantly affected. This is the reason for the reduction of the aerodynamic drag and lift on the train. In addition, the reduction effects become more obvious when the thickness of the boundary layer increases. The experimental results obtained could serve as a calibration of aerodynamic forces for wind tunnel tests on high-speed trains.
Evidence of the Involvement of Nematostoma parasiticum in Herpotrichia Needle Browning of Abies balsamea
Authors: Lerat Sylvain , Roussin-Léveillée Charles , Sidibé Amadou , Moffett Peter , Beaulieu Carole
Published: May 2023

Herpotrichia needle browning (HNB) is a disease that affects several species of fir trees in Europe and North America. HNB was first described by Hartig in 1884, who isolated a fungal pathogenic agent identified as responsible for the disease. This fungus was later named Herpotrichia parasitica but is currently named Nematostoma parasiticum. However, the identity of the pathogens causing HNB is regularly questioned and, to date, the true causal agent of this disease has not been definitely established. The present study aimed to identify the fungal populations present in needles of Christmas fir trees (Abies balsamea) and to correlate them with needle health status using robust molecular methods. PCR primers specific to N. parasiticum allowed detection of the presence of this fungus in DNA samples from symptomatic needles. Furthermore, high-throughput sequencing (Illumina MiSeq) clearly showed that N. parasiticum was associated with symptomatic needles. However, high-throughput sequencing results revealed that the presence of other species such as Sydowia polyspora and Rhizoctonia sp. may also correlate with the development of HNB. A diagnostic tool, based on quantitative PCR using a probe, was then developed to detect and quantify N. parasiticum in DNA samples. The efficacy of this molecular approach was validated through the detection of the pathogenic agent in symptomatic needle samples as well as in nonsymptomatic needles collected in trees affected by HNB. In contrast, N. parasiticum could not be found in needles from healthy trees. The present study argues for the importance of N. parasiticum in causing HNB symptoms.
Commercial Hard Squash Cultivars Exhibit Differences in Susceptibility to Phytophthora Crown Rot
Authors: Perla David E. , Hayden Zachary D. , Hausbeck Mary K.
Published: May 2023

Crown rot and fruit rot, caused by the oomycete Phytophthora capsici, limit the yield and quality of hard squash grown for processing. In a 2-year field study, we compared four Butternut types ( Cucurbita moschata), two Delicious varietal Hubbard types ( Cucurbita maxima), and six Kabocha types ( C. maxima) for crown rot resistance and fruit characteristics relevant to processing including mesocarp soluble solids, percentage of dry matter, and average fruit weight in 2019 and 2020. To evaluate crown rot, plants were inoculated in replicated field trials. The C. moschata cultivars Dickinson, Buckskin, New England Cheddar, and Ultra Butternut had significantly less plant death in both years (<15%) than other cultivars. Significantly fewer Thunder plants died in 2020 (59.6%) compared with the Kabocha cultivars Sweet Mama (>94.2%), Delica (≥92.3%), and Sunshine (≥90.4%) and had a lower relative area under the disease progress curve value (≤22.4) in both years. In noninoculated field trials, mature fruits were assessed for fruit characteristics. Of the resistant C. moschata cultivars, only Ultra Butternut exhibited similar °Brix to NK 580 in both years and had comparable or greater dry matter and fruit weight. Kabocha cultivars with moderate crown rot susceptibility (i.e., Thunder) exhibited higher °Brix and dry matter and smaller fruit weight compared with NK 580 each year. Integrated management programs can be advanced by selecting cultivars with crown rot resistance. Further evaluation of desirable yield and quality characteristics of the resistant cultivars could accelerate acceptance of these cultivars by growers and processors.
Residents, Responsibility, and Error: How Residents Learn to Navigate the Intersection
Authors: Shepherd Lisa , Chilton Stephanie , Cristancho Sayra M.
Published: May 2023

Purpose

As a competency of Canadian postgraduate education, residents are expected to be able to promptly disclose medical errors and assume responsibility for and take steps to remedy these errors. How residents, vulnerable through their inexperience and hierarchical team position, navigate the highly emotional event of medical error is underexplored. This study examined how residents experience medical error and learn to become responsible for patients who have faced a medical error.

Method

Nineteen residents from a breadth of specialties and years of training at a large Canadian university residency program were recruited to participate in semistructured interviews between July 2021 and May 2022. The interviews probed their experience of caring for patients who had experienced a medical error. Data collection and analysis were conducted iteratively using a constructivist grounded theory method with themes identified through constant comparative analysis.

Results

Participants described their process of conceptualizing error that evolved throughout residency. Overall, the participants described a framework for how they experienced error and learned to care for both their patients and themselves following a medical error. They outlined their personal development of understanding error, how role modeling influenced their thinking about error, their recognition of the challenge of navigating a workplace environment full of opportunities for error, and how they sought emotional support in the aftermath.

Conclusions

Teaching residents to avoid making errors is important, but it cannot replace the critical task of supporting them both clinically and emotionally when errors inevitably occur. A better understanding of how residents learn to manage and become responsible for medical error exposes the need for formal training as well as timely, explicit discussion and emotional support both during and after the event. As in clinical management, graded independence in error management is important and should not be avoided because of faculty discomfort.
Omission of Pelvic Examination Before Gender-Affirming Hysterectomy and Vaginectomy
Authors: Murphy Ellen C. , Kim Youngwu , Weinstein Milena M.
Published: May 2023

Surgeons may be performing pelvic examinations on transgender patients before gender-affirming pelvic surgery (hysterectomy and vaginectomy) without a clinically significant indication. A retrospective cohort study was conducted at a single-institution academic referral center comparing 30-day perioperative outcomes of all 62 gender-affirming pelvic surgeries, including hysterectomy alone, hysterectomy with vaginectomy, and vaginectomy alone, between April 2018 and March 2022. More than half (53.2%, n=33) of the 62 patients did not have an in-office, preoperative, internal pelvic examination within 1 year of gender-affirming surgery. There were no significant differences in patient characteristics nor 30-day perioperative outcomes between the examined and examination-omitted groups, suggesting that omission of a preoperative pelvic examination is probably safe before gender-affirming hysterectomy and vaginectomy, minimizing barriers to gender-affirming surgical care.
Detecting the Change in Total Circulatory Flow with a Wireless, Wearable Doppler Ultrasound Patch: A Pilot Study
Authors: Munding Chelsea E. , Kenny Jon-Émile S. , Yang Zhen , Clarke Geoffrey , Elfarnawany Mai , Eibl Andrew M. , Eibl Joseph K. , Nalla Bhanu , Atoui Rony
Published: May 2023

OBJECTIVE:

Measuring fluid responsiveness is important in the management of critically ill patients, with a 10–15% change in cardiac output typically being used to indicate “fluid responsiveness.” Ideally, these changes would be measured noninvasively and peripherally. The aim of this study was to determine how the common carotid artery (CCA) maximum velocity changes with total circulatory flow when confounding factors are mitigated and determine a value for CCA maximum velocity corresponding to a 10% change in total circulatory flow.

DESIGN:

Prospective observational pilot study.

SETTING:

Patients undergoing elective, on-pump coronary artery bypass grafting (CABG) surgery.

PATIENTS:

Fourteen patients were referred for elective coronary artery bypass grafting surgery.

INTERVENTIONS:

Cardiopulmonary bypass (CPB) pump flow changes during surgery, as chosen by the perfusionist.

MEASUREMENTS:

A hands-free, wearable Doppler patch was used for CCA velocity measurements with the aim of preventing user errors in ultrasound measurements. Maximum CCA velocity was determined from the spectrogram acquired by the Doppler patch. CPB flow rates were recorded as displayed on the CPB console, and further measured from the peristaltic pulsation frequency visible on the recorded Doppler spectrograms.

MAIN RESULTS:

Changes in CCA maximum velocity tracked well with changes in CPB flow. On average, a 13.6% change in CCA maximum velocity was found to correspond to a 10% change in CPB flow rate.

CONCLUSIONS:

Changes in CCA velocity may be a useful surrogate for determining fluid responsiveness when user error can be mitigated.
Screening approaches for cervical cancer in Mozambique in HIV positive and negative women
Authors: Sineque Alberto , Catalao Carlos , Ceffa Susanna , Fonseca Ana Maria , Parruque Fernanda , Guidotti Giovanni , Massango Cacilda , Carrilho Carla , Bicho Clara , Rangeiro Ricardina , Orlando Stefano , Marazzi Maria Cristina , Lorenzoni Cesaltina , Ciccacci Fausto
Published: May 2023

Objective

Cervical cancer (CC) is a global health issue, in Mozambique, 5300 new cases and 3800 deaths are reported each year. The WHO recommends the introduction of HPV molecular testing for CC screening, but Mozambique uses an approach based on visual inspection with acetic acid (VIA). This study aims to evaluate the feasibility of high-risk HPV (hrHPV) testing compared to actual approaches in Mozambique.

Methods

An observational study was carried out in the DREAM center in Zimpeto, Mozambique. Women aged 30–55 were included. HPV testing was performed with the Cobas HPV test. They were then screened with the current national recommendations based on VIA. Cryotherapy was performed on-site or referred for colposcopy if necessary.

Results

In the period, 1207 women were enrolled, 47.8% HIV+; 124 (10.3%) VIA+, and HPV DNA test was positive in 325 (26.9%) women. HPV positivity rates were higher in HIV-infected women. In the sample, 52.8% of the 124 VIA+ women were HPV uninfected and underwent unnecessary cryotherapy or colposcopy. Meanwhile, 24.7% of the 1083 VIA− women were actually HPV infected. In comparison, a screen, triage and treat approach based on hrHPV testing would only test and treat the 325 HPV-infected women.

Conclusion

The study found high rates of hrHPV infection, particularly in HIV-positive women, with many concurrent or multiple infections. The current screening method misses important hrHPV infections and results in many unnecessary treatments. These results support the use of HPV molecular testing as the initial screening test for CC.
Clinical Characteristics and Survival Analysis of Patients With Second Primary Malignancies After Hepatocellular Carcinoma Liver Transplantation
Authors: Ding Qingbao , Wang Keyu , Li Yupeng , Peng Peng , Zhang Dongyuan , Chang Donglei , Wang Wentao , Ren Lei , Tang Fang , Li Ziqiang
Published: May 2023

Background:

Second primary malignancies (SPMs) after liver transplantation (LT) are becoming the leading causes of death in LT recipients. The purpose of this study was to explore prognostic factors for SPMs and to establish an overall survival nomogram.

Methods:

A retrospective analysis was conducted of data from the Surveillance, Epidemiology, and End Results (SEER) database on adult patients with primary hepatocellular carcinoma who had undergone LT between 2004 and 2015. Cox regression analysis was used to explore the independent prognostic factors for SPMs. Nomogram was constructed using R software to predict the overall survival at 2, 3, and 5 years. The concordance index, calibration curves, and decision curve analysis were used to evaluate the clinical prediction model.

Results:

Data from a total of 2078 patients were eligible, of whom 221 (10.64%) developed SPMs. A total of 221 patients were split into a training cohort (n=154) or a validation cohort (n=67) with a 7:3 ratio. The 3 most common SPMs were lung cancer, prostate cancer, and non-Hodgkin lymphoma. Age at initial diagnosis, marital status, year of diagnosis, T stage, and latency were the prognostic factors for SPMs. The C-index of the nomogram for overall survival in the training and validation cohorts were 0.713 and 0.729, respectively.

Conclusions:

We analyzed the clinical characteristics of SPMs and developed a precise prediction nomogram, with a good predictive performance. The nomogram we developed may help clinicians provide personalized decisions and clinical treatment for LT recipients.
Association Between Statin Exposure and Incidence and Prognosis of Prostate Cancer
Authors: Cao Zipei , Yao Jie , He Yujing , Lou Dandi , Huang Jianing , Zhang Yeyuan , Chen Meiling , Zhou Zhizhen , Zhou Xiaomei
Published: May 2023

It is widely thought that statins have huge therapeutic potential against prostate cancer (PCA). This study aimed to investigate the effect of statin exposure on PCA incidence and prognosis. PubMed, Web of Science, Embase, and Cochrane databases were searched for observational studies on the association between statin exposure and PCA from inception until July 2022. The primary endpoints were the incidence of PCA and the survival rate. A total of 21 studies were included in this meta-analysis. The pooled estimates showed that exposure to hydrophilic statins was not associated with the incidence of PCA (odds ratio [OR]=0.94, 95% CI=0.88-1.01, P=0.075), while the incidence of PCA was significantly decreased in populations exposed to lipophilic statins compared with the nonexposed group (OR=0.94, 95% CI=0.90-0.98, P=0.001), mainly in Western countries (OR=0.94, 95% CI=0.91-0.98, P=0.006). Subgroup analysis showed that simvastatin (OR=0.83, 95% CI=0.71-0.97, P=0.016) effectively reduced the incidence of PCA. The prognosis of PCA in patients exposed to both hydrophilic (hazard ratio [HR]=0.57, 95% CI=0.49-0.66, P<0.001) and lipophilic (HR=0.65, 95% CI=0.58-0.73, P<0.001) statins were better than in the nonexposed group, and this improvement was more significant in the East than in Western countries. This study demonstrates that statins can reduce the incidence of PCA and improve prognosis, and are affected by population region and statin properties (hydrophilic and lipophilic).
The severity of COVID-19 across the spectrum of HIV
Authors: Miller Kathleen W. , Gandhi Rajesh T.
Published: May 2023

Purpose of review

We review the intersection between the HIV and COVID-19 pandemics, particularly the impact of HIV infection on the development of severe COVID-19.

Recent findings

Studies early in the COVID-19 pandemic did not find a clear link between HIV infection and increased COVID-19 severity or mortality. People with HIV (PWH) were more likely to have severe COVID-19, but much of the risk for worse outcomes was related to high rates of comorbidities and social determinants of health. Although comorbidities and social determinants of health are certainly critically important reasons for severe COVID-19 among PWH, recent large studies have found HIV infection – particularly when the CD4 cell count is low or HIV RNA is not suppressed – is an independent risk factor for COVID-19 severity. The link between HIV and severe COVID-19 highlights the need to diagnose and treat HIV as well as the importance of COVID-19 vaccination and treatment among PWH.

People with HIV have faced increased challenges during the COVID-19 pandemic because of high rates of comorbidities and social determinants of health as well as the impact of HIV on COVID-19 severity. Information on the intersection of the two pandemics has been crucial to improving care for people with HIV.
Assessing the astigmatism-reducing effect of toric intraocular lenses in eyes with low astigmatism: randomized masked bilateral comparison
Authors: Hienert Julius , Ruiss Manuel , Hirnschall Nino , Findl Oliver
Published: May 2023

Purpose:

To evaluate the astigmatism-reducing effect of toric intraocular lenses (IOLs) for low amounts of corneal astigmatism.

Setting:

Hanusch Hospital, Vienna, Austria.

Design:

Randomized, masked, controlled trial with bilateral comparison.

Methods:

Patients scheduled for bilateral cataract surgery and a corneal astigmatism in both eyes between 0.75 diopters (D) and 1.5 D were included in this study. The first eye was randomized to receive either a toric IOL or a nontoric IOL, and the contralateral eye received the other type of IOL. At the follow-up visits, optical biometry, corneal measurements with tomography and topography, autorefraction, subjective refraction, corrected and uncorrected distance visual acuity (CDVA/UDVA) with ETDRS charts and a questionnaire were performed.

Results:

58 eyes were included in the study. Postoperative median UDVA was 0.00 (logMAR) in the toric eyes and 0.10 in the nontoric eyes (P = .03). The median CDVA was 0.00 in both groups (P = .60). Median residual astigmatism determined by subjective refraction and autorefraction in the toric eyes was 0.25 D and 0.50 D, respectively (P = .04), and 0.50 D and 1.00 D in the nontoric eyes, respectively (P < .001).

Conclusions:

The use of a toric IOL appears to be appropriate from a threshold value of approximately 0.75 D preoperative corneal astigmatism. Further studies in a larger patient population are needed to confirm these results.
Mediators of the association between childhood trauma and pain sensitivity in adulthood: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network analysis
Authors: Pierce Jennifer , Harte Steven E. , Afari Niloofar , Bradley Catherine S. , Griffith James W. , Kim Jayoung , Lutgendorf Susan , Naliboff Bruce D. , Rodriguez Larissa V. , Taple Bayley J. , Williams David , Harris Richard E. , Schrepf Andrew ,   on behalf of the MAPP Research Network
Published: May 2023

Urologic chronic pelvic pain syndrome (UCPPS) is a complex, debilitating condition in which patients often report nonpelvic pain in addition to localized pelvic pain. Understanding differential predictors of pelvic pain only vs widespread pain may provide novel pathways for intervention. This study leveraged baseline data from the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network's Symptom Pattern Study to investigate the impact of childhood sexual and nonsexual violent trauma on pelvic and nonpelvic pain sensitivity among adult patients with UCPPS, as well as potential mediators of this association. Study participants who met inclusion criteria for UCPPS completed questionnaires assessing childhood and recent trauma, affective distress, cognitive dysfunction, and generalized sensory sensitivity. Experimental pain sensitivity was also evaluated using standardized pressure pain applied to the pubic region and the arm. Bivariate analyses showed that childhood violent trauma was associated with more nonviolent childhood trauma, more recent trauma, poorer adult functioning, and greater pain sensitivity at the pubic region, but not pain sensitivity at the arm. Path analysis suggested that childhood violent trauma was indirectly associated with pain sensitivity at both sites and that this indirect association was primarily mediated by generalized sensory sensitivity. More experiences of recent trauma also contributed to these indirect effects. The findings suggest that, among participants with UCPPS, childhood violent trauma may be associated with heightened pain sensitivity to the extent that trauma history is associated with a subsequent increase in generalized sensory sensitivity.
Deep learning–guided postoperative pain assessment in children
Authors: Fang Jihong , Wu Wei , Liu Jiawei , Zhang Sicheng
Published: May 2023

Current automated pain assessment methods only focus on infants or youth. They are less practical because the children who suffer from postoperative pain in clinical scenarios are in a wider range of ages. In this article, we present a large-scale Clinical Pain Expression of Children (CPEC) dataset for postoperative pain assessment in children. It contains 4104 preoperative videos and 4865 postoperative videos of 4104 children (from 0 to 14 years of age), which are collected from January 2020 to December 2020 in Anhui Provincial Children's Hospital. Moreover, inspired by the dramatic successful applications of deep learning in medical image analysis and emotion recognition, we develop a novel deep learning–based framework to automatically assess postoperative pain according to the facial expression of children, namely Children Pain Assessment Neural Network (CPANN). We train and evaluate the CPANN with the CPEC dataset. The performance of the framework is measured by accuracy and macro-F1 score metrics. The CPANN achieves 82.1% accuracy and 73.9% macro-F1 score on the testing set of CPEC. The CPANN is faster, more convenient, and more objective compared with using pain scales according to the specific type of pain or children's condition. This study demonstrates the effectiveness of deep learning–based method for automated pain assessment in children.
Family-Related Life Events as Predictors of Labor Market Marginalization Trajectories
Authors: Wang Mo , Raza Auriba , Narusyte Jurgita , Silventoinen Karri , Böckerman Petri , Svedberg Pia , Ropponen Annina
Published: May 2023

Objectives

The aims of the study are to investigate trajectories of labor market marginalization (LMM) and to examine the associations between family-related life events and LMM trajectories while accounting for familial factors.

Methods

This is a prospective cohort study of 37,867 Swedish twins. Data were analyzed by group-based trajectory modeling. Associations of family-related life events with trajectory groups were estimated by multinomial logistic regression.

Results

Most participants had no or low levels of LMM. Individuals who stayed married over time or changed from single without children to married with children had a decreased risk of LMM. The risk of LMM over time was higher among individuals who changed from married to being single.

Conclusions

Being or getting married as well as having children decreases the risk of LMM while divorce is a risk factor for LMM.
Pulmonary Artery Dual-Lumen Cannulation Versus Two Cannula Percutaneous Extracorporeal Membrane Oxygenation Configuration in Right Ventricular Failure
Authors: Ritter Lindsay A. , Haj Bakri Mouaz , Fahey Heather C. , Sanghavi Kavya K. , Kallur Akhil , Bien-Aime Fred , Sallam Tariq , Alassar Aiman , Balsara Keki , Kitahara Hiroto , MacGillivray Thomas E. , Zaaqoq Akram M.
Published: May 2023

Refractory right ventricular failure has significant morbidity and mortality. Extracorporeal membrane oxygenation is indicated when medical interventions are deemed ineffective. However, it is still being determined if one configuration is better. We conducted a retrospective analysis of our institutional experience comparing the peripheral veno-pulmonary artery (V-PA) configuration versus the dual-lumen cannula with the tip in the pulmonary artery (C-PA). The analysis of a cohort of 24 patients (12 patients in each group). There was no difference in survival after hospital discharge (58.3% in the C-PA group compared to 41.7% in the V-PA group, p = 0.4). Among the C-PA group, there was a statistically significant shorter ICU length of stay (23.5 days [interquartile range {IQR} = 19–38.5] vs. 43 days [IQR = 30–50], p = 0.043) and duration of mechanical ventilation (7.5 days [IQR = 4.5–9.5] compared to (16.5 days [IQR = 9.5–22.5], p = 0.006) in the V-PA group. In the C-PA group, there were lower incidents of bleeding (33.33% vs. 83.33%, p =0.036) and combined ischemic events (0 vs. 41.67%, p = 0.037). In our single-center experience, the C-PA configuration might have a better outcome than the V-PA one. Further studies are needed to confirm our findings.
Cold Oxygenated Machine Perfusion Improves Functional Survival of Slaughterhouse Porcine Hearts
Authors: Kaffka Genaamd Dengler Selma E. , Mishra Mudit , van Tuijl Sjoerd , de Jager Saskia C. A. , Sluijter Joost P. G. , Doevendans Pieter A. , van der Kaaij Niels. P.
Published: May 2023

The aim of our study was to explore the effect of cold oxygenated machine perfusion in slaughterhouse porcine hearts on functional myocardial survival compared to static cold storage (SCS). Seventeen hearts were harvested from Dutch Landrace Hybrid pigs, which were sacrificed for human consumption and randomly assigned to the 4 hours SCS group (N = 10) or the 4 hours cold oxygenated machine perfusion group (N = 7). Hearts were perfused with a homemade Heart Solution with a perfusion pressure of 20–25 mm Hg to achieve a coronary flow between 100 and 200 ml/minute. After 4 hours of preservation, all hearts were functionally assessed during 4 hours on a normothermic, oxygenated diluted whole blood (1:2) loaded heart model. Survival was defined by a cardiac output above 3 L with a mean aortic pressure above 60 mm Hg. Survival was significantly better in the cold oxygenated machine perfusion group, where 100% of the hearts reached the 4 hours end-point, as compared with 30% in the SCS group (p = 0.006). Interestingly, warm ischemic time was inversely related to survival in the SCS group with a correlation coefficient of −0.754 (p = 0.012). Cold oxygenated machine perfusion improves survival of the slaughterhouse porcine heart.
Four-Factor Prothrombin Complex Concentrate in Left Ventricular Assist Device Implantation: Inverse Propensity Score-Weighted Analysis
Authors: Monaco Fabrizio , Licheri Margherita , Barucco Gaia , De Bonis Michele , Lapenna Elisabetta , Pieri Marina , Zangrillo Alberto , Ortalda Alessandro ,   Collaborators
Published: May 2023

We compare the effect of intraoperative administration of four-factor prothrombin complex concentrates (PCCs) versus fresh frozen plasma (FFP) on major bleeding, transfusions, and complications. Out of 138 patients undergoing left ventricle assist device (LVAD) implantation, 32 received PCCs as first-line hemostatic agents and 102 FFP (standard group). The crude treatment estimates indicated that, compared with the standard group, the PCC group required more FFP units (odds ratio [OR]: 4.17, 95% confidence interval [CI]: 1.58–11; p = 0.004) intraoperatively, whereas a greater number of patients received FFP at 24 hours (OR: 3.01, 95% CI: 1.19–7.59; p = 0.021) and less packed red blood cells (RBC) at 48 hours (OR: 0.61, 95% CI: 0.01–1.21; p = 0.046). After the inverse probability of treatment weighting (IPTW) adjusted analyses, in the PCC group there was still a higher number of patients who required FFP (OR: 2.9, 95% CI: 1.02–8.25; p = 0.048) or RBC (OR: 6.23, 95% CI: 1.67–23.14; p = 0.007] at 24 hours and RBC at 48 hours (OR: 3.09, 95% CI: 0.89–10.76; p = 0.007). Adverse events and survival were similar before and after the ITPW adjustment. In conclusion, the PCCs, although relatively safe with respect to thrombotic events, were not associated with a reduction of major bleeding and blood product transfusions.