bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring Practices After Pediatric Liver Transplantation
Authors: Slowik Voytek , Ryan Jamie L. , Shah Amit A. , Lobritto Steven J.
Published: August 2023

Objectives:

This study sought to understand the current monitoring practices after pediatric liver transplantation (LT), specifically regarding follow-up clinic visits, outpatient laboratory testing, protocol biopsies, and diagnostic imaging, and to identify potential center and provider characteristics associated with such practices.

Methods:

A cross-sectional survey of pediatric LT providers at centers participating in the Society of Pediatric Liver Transplantation (SPLIT) registry was conducted from February 2020 to April 2021.

Results:

The overall response rate was 79% (38/48 SPLIT centers), with the majority representing large volume centers (>10 LTs per year). Frequency of clinic visits and laboratory monitoring varied by center, but all centers decreased frequency after the first post-transplant year. The most common practice included an annual clinic visit and laboratory sampling every 2–3 months. Surveillance liver biopsy is seldom done during the first post-transplant year, while being routinely performed by 50% of centers after this time period. Centers forgoing surveillance biopsies assert that the results would likely not change management. Only 39% of centers have a hepatologist perform the liver biopsy while the remaining centers consult interventional radiology. Most diagnostic imaging is obtained only as needed. Routine abdominal ultrasounds were obtained by only 50% of responding centers after the first year post-transplant.

Conclusions:

SPLIT centers vary widely in the routine management of LTs after the first year post-transplant. While common themes emerge, future studies will be needed to connect protocols to outcomes to determine best practice.
The Diagnostic Concept of Unipolar Mania
Authors: Bartoli Francesco
Published: August 2023

Although the traditional nosological view interprets mania as strictly connected with depression in the context of manic-depressive illness, unipolar mania (UM), that is, the lifetime occurrence of mania or hypomania in the absence of depression, has been proposed as a necessary diagnostic entity. Epidemiological data estimate that at least 5% of people with type I bipolar disorder never experienced depression. These subjects are more often males with a hyperthymic temperament, a younger age at onset, and more psychotic features. Current classification systems do not formally recognize UM, but different definitions of mania without depression have been proposed. UM should be assessed according to the number of mood episodes, the predominance of manic or hypomanic episodes, and its clinical course. More generally, UM should be considered in the context of an affective spectrum including different clinical phenotypes based on the predominance of depressive or manic symptoms. Additional clinical and epidemiological research in this field is needed.
Medicolegal Death Investigation of Railroad-Related Fatalities
Authors: Brooks Jared , Grande Abigail , Prahlow Joseph A. , Brown Theodore
Published: August 2023

Railroad-related fatalities in the United States are increasing. A paucity of literature exists regarding the medicolegal death investigation of railroad-related deaths. We report on a subset of deaths in western Michigan, propose protocols for investigating train-related deaths, and propose a stepwise approach for the medicolegal investigation of railroad-related fatalities. Fourteen railroad-related fatalities from 2015 to 2019 were reviewed. Each case was analyzed for demographics, investigative components, train variables, and death certification. The average age was 32 years. Nine decedents involved pedestrians versus trains, and 5 involved motor vehicles versus trains. Male victims were more common, and 50% of the cases were associated with mental illness or recent stressors. Accident was the most common manner of death. With the exception of basic weather conditions, the remaining investigative variables were rarely reported. Image and audio recordings were taken in 3 cases, but railroad companies refused to allow the recordings to be viewed by the medical examiner. We conclude that in addition to a thorough medicolegal death scene investigation and postmortem examination, audio/video recordings are crucial components of death certification in railroad-related fatalities and advocate that medical examiners/coroners be given the legal right to view and retain them.
Acute Organophosphate Poisoning Case Review With Consideration of Off-Gassing During Postmortem Examination
Authors: Hanson Courtney , Huddle Lauren N. , Kockanowski Julia , Whaley Kevin D.
Published: August 2023

Although self-harm via ingestion of organophosphorus compounds is relatively common in the developing world, it is rare in the United States. This article reviews the signs and symptoms associated with acute organophosphate poisoning and highlights the effects of organophosphate off-gassing during postmortem examinations to increase awareness of this potentially dangerous workplace exposure.

Paramedics responded to a 42-year-old man with pulseless electrical activity. Spontaneous circulation was restored after aggressive resuscitation. Before loss of consciousness, the patient exhibited diaphoresis, vomiting, and diarrhea. Upon admission, the patient had a Glasgow Coma Scale score of 3. Significant laboratory values included a pH of 6.8, pco
2 of 72 mm Hg, and lactic acid of 21.8 mmol/L. Electrocardiography suggested inferior ST-elevation myocardial infarction. Electroencephalogram revealed severe cerebral dysfunction. The patient died shortly thereafter.

Scene investigation revealed suicidal ideations, which included a snapshot of a bottle containing granular sediment associated with statements that he had imbibed fertilizer. During the postmortem examination, the decedent exuded a petroleum-like odor. In addition, autopsy personnel developed symptoms consistent with organophosphate exposure.

A reported history of suspected organophosphate exposure in a decedent should prompt increased safety practices to avoid potential harm to autopsy personnel.
PEComa of the Adrenal Gland
Authors: Wakefield Craig B. , Sadow Peter M. , Hornick Jason L. , Fletcher Christopher D.M. , Barletta Justine A. , Anderson William J.
Published: August 2023

PEComas are a family of mesenchymal neoplasms composed of histologically distinctive perivascular epithelioid cells which demonstrate myomelanocytic differentiation. PEComas of the adrenal gland are very rare and can represent a considerable diagnostic challenge given their morphologic overlap with more common adrenal cortical neoplasms. We present the clinicopathologic features of 7 primary adrenal PEComas. The cohort comprised 5 male and 2 female patients with a median age of 63 years (range: 31 to 71 y). One patient had Birt-Hogg-Dubé syndrome and another had Lynch syndrome; however, none had a history of tuberous sclerosis complex. Histologically, tumors showed nested and/or sheet-like growth and epithelioid cytomorphology with pale-to-eosinophilic granular cytoplasm. Two tumors had an admixed spindle cell component. There was a median of 4 mitoses per 10 HPFs (range: 0 to 8). Necrosis was present in 4 tumors and lymphovascular invasion in 1. Four tumors were classified as malignant. By immunohistochemistry, tumors were positive for HMB-45 (3/7), MITF (3/3), Melan-A (3/7), smooth muscle actin (5/7), desmin (5/7), and caldesmon (1/1). Two tumors were positive for TFE3 (2/4). Inhibin and SF1 were negative in all tumors assessed (0/6). Of 3 patients with available clinical follow-up information, 1 patient developed locally recurrent and metastatic disease (at 18 mo) and was alive with persistent disease at the last follow-up. Two patients had no recurrent or metastatic disease at the last follow-up (60 and 25 mo). Although PEComas of the adrenal gland are rare, pathologists need to be alert to this entity in the differential diagnosis of primary adrenocortical neoplasms. In suspected cases, the judicious use of melanocytic and smooth muscle markers, in addition to TFE3 and markers of adrenocortical differentiation (such as SF1 and inhibin) can assist in diagnosis. As in PEComas arising at other visceral sites, an association with tuberous sclerosis complex seems to be uncommon.
Adenoid Ameloblastoma Shares Clinicopathologic, Immunohistochemical, and Molecular Features With Dentinogenic Ghost Cell Tumor
Authors: Xue Jiang , Zhang Wenyi , Zhang Jianyun , Bai Jiaying , Zhang Aobo , Guo Xiaowen , Sun Lisha , Li Tiejun
Published: August 2023

The updated classification of odontogenic tumors by the World Health Organization (WHO) has included adenoid ameloblastoma (AA) as a distinct entity. However, distinguishing between AA and dentinogenic ghost cell tumor (DGCT) can still be challenging due to their significant morphologic similarities. In this study, we aimed to compare the clinicopathologic, immunohistochemical, and molecular characteristics of AA and DGCT to aid in their differentiation and to shed light on their pathologic mechanisms. Thirteen cases of AA and 14 cases of DGCT (15 samples) were analyzed, along with 11 cases of adenomatoid odontogenic tumor (AOT) and 18 cases of conventional ameloblastoma (AM) for comparative purposes. The study found that AA and DGCT shared a similar long-term prognosis. Immunohistochemically, all cytokeratins detected, except CK8/18, were not statistically significant in differentiating AA and DGCT, while there was a statistically significant difference in the immunophenotype of CK7 and CK10/13 between AA and AM. Nuclear β-catenin accumulation were detected in all cases of AA and DGCT, while AOTs and AMs exhibited cytoplasmic β-catenin. Molecularly, CTNNB1 hotspot mutations were found in only 1 case of AA (1/13), but not found in the other 3 types of tumors. BRAF p.V600E mutation was positive in 2/13 (15%) AA, 1/15 (7%) DGCT, and 2/11 (18%) AOT cases. In comparison, conventional AM was positive for BRAF p.V600E mutation in 94% (17/18) of cases, while KRAS mutations were detected in 63% (7/11) of AOT cases. The study suggests that the so-called AA is a rare benign tumor that exhibits clinical, immunohistochemical, and molecular features similar to DGCTs. Based on these findings, AA should not be categorized as a standalone entity solely based on the presence of whorls/morules and cribriform/duct-like structures. Further studies are needed to investigate the pathologic mechanisms of these tumors and to identify potential therapeutic targets.
Factors involved in higher knee extension torque induced by repetitive peripheral magnetic stimulation
Authors: KAMIUE∗ Masanori , ITO∗ Tomotaka , TSUBAHARA∗ Akio , KISHIMOTO∗ Tomoya
Published: August 2023

Objective

The study aimed to determine the relationship between knee extension torque induced by repetitive peripheral magnetic stimulation (rPMS) and the characteristics of the participants.

Design

This was a basic study with non-invasive intervention. Knee extension torque induced by rPMS (rPMS-induced torque) and maximum voluntary contraction (MVC) were measured. Stepwise method of multiple regression was performed to determine the factors affecting rPMS-induced torque at 100% intensity and rPMS-induced torque divided by MVC (%MVC). Subcutaneous fat thickness, VL muscle thickness measured by ultrasound, MVC, and mean power frequency of electromyography (EMG) during MVC were selected as independent variables.

Results

rPMS was applied to the right vastus lateralis (VL) of 30 young healthy adults (average age, 21.1 ± 0.3 years). In the multiple regression analysis, rPMS-induced torque (p < 0.001) was shown to be independently and significantly associated with MVC (β = 0.510), subcutaneous fat thickness (β = -0.358), and VL muscle thickness (β = 0.208), while %MVC value (p < 0.05) was independently and significantly associated with VL muscle thickness (β = 1.059).

Conclusion

rPMS-induced torque decreases with thicker subcutaneous fat and increases with stronger MVC or with thicker muscle.
Effect of Knee Hyperextension on Femoral Cartilage Thickness in Stroke Patients
Authors: Korkusuz Süleyman , Kibar Sibel , Özgören Nihat , Arıtan Serdar , Seçkinoğulları Büşra , Balkan Ayla Fil
Published: August 2023

Objective

Knee hyperextension is one of the most common compensatory mechanisms in stroke patients. The first aim of the study was to measure knee hyperextension and femoral cartilage thickness in stroke patients. The second aim was to compare the femoral cartilage thickness of the paretic and nonparetic limbs in stroke patients with and without knee hyperextension.

Design

Forty stroke patients were included in the study. The patients were divided into two groups according to the presence of knee hyperextension based on kinematic analyses performed during walking with a three-dimensional motion analysis system. The medial femoral cartilage, lateral femoral cartilage, and intercondylar cartilage thicknesses of the paretic and nonparetic sides of the patients were measured by ultrasonography.

Results

In the study group, medial femoral cartilage, intercondylar, and lateral femoral cartilage thicknesses were less on the paretic side than on the nonparetic side, while the femoral cartilage thicknesses on the paretic and nonparetic sides were similar in the control group. Paretic side medial femoral cartilage and intercondylar thicknesses were less in the study group compared with the control group, and lateral femoral cartilage thickness was similar between the two groups.

Conclusions

Knee hyperextension during walking causes femoral cartilage degeneration in stroke patients.

Clinical Trial code: NCT05513157
Pediatric ED Saves: Analyzing the ED Screen of Direct Admissions
Authors: Ramirez-Cueva Fatima , Prusky Grinberg Gary , Kuchinski Ann Marie , Gibson Robert , Xu Hongyan , Zhang Li Fang , Seeyave Desiree
Published: August 2023

Introduction:

Direct admissions (DAs) are a routine hospital entry portal with few guidelines to assess patient safety during this process. This study assessed the effectiveness of an institutional screen for patients presenting as DA. It investigated patient variables that may predict appropriateness for DA and those at high risk for deterioration.

Methods:

The study includes patients who received the institutional screen between June 1, 2019, and May 31, 2020. We placed charts into three groups: group 1 (stable), group 2 (unstable), and group 3 (stable then transferred to pediatric intensive care unit within 6 hours). We assessed effectiveness by calculating sensitivity, specificity, and predictive values. We used comparative analysis between groups to identify patients safe for DA and those at high risk for deterioration,

Results:

The screen was 80% sensitive and 100% specific, predicting 97.7% of stable patients. Of the 652 charts reviewed, 384 met the inclusion criteria. Group 1 (31.60, 26.45%, 5.23%) had lower respiratory rate, respiratory diagnosis, and oxygen requirement compared to group 2 (45.00, 78.13%, 15.63%) and group 3 (44.50, 75.00%, 50.00%). For SpO2, group 1 (98.70) was higher than group 2 (96.03). For the Pediatric Early Warning Score, group 2 (1.72) was higher than group 1 (0.31) and group 3 (0.63).

Conclusions:

The institutional screen is an effective tool to identify patients presenting as DA needing immediate emergency department intervention and/or pediatric intensive care unit care. The screen benefits patients with a respiratory diagnosis, oxygen requirement, high respiratory rate or low SpO2.
RESPIRATION-RELATED VARIATIONS IN CENTRAL VENOUS PRESSURE AS PREDICTORS OF FLUID RESPONSIVENESS IN SPONTANEOUSLY BREATHING PATIENTS
Authors: Bourel Claire , Durand Arthur , Ter Schiphorst Benoit , Martin Claire , Onimus Thierry , De Jonckheere Julien , Howsam Michael , Pierre Alexandre , Favory Raphael , Preau Sebastien
Published: August 2023

Objective: The hemodynamic parameters used to accurately predict fluid responsiveness (FR) in spontaneously breathing patients (SB) require specific material and expertise. Measurements of the central venous pressure (CVP) are relatively simple and, importantly, are feasible in many critically ill patients. We analyzed the accuracy of respiration-related variations in CVP (vCVP) to predict FR in SB patients and examined the optimization of its measurement using a standardized, deep inspiratory maneuver. Patients and Methods: We performed a monocentric, prospective, diagnostic evaluation. Spontaneously breathing patients in intensive care units with a central venous catheter were prospectively included. The vCVP was measured while the patient was spontaneously breathing, both with (vCVP-st) and without (vCVP-ns) a standardized inspiratory maneuver, and calculated as: Minimum inspiratory v-wave peak pressure − Maximum expiratory v-wave peak pressure. A passive leg raising-induced increase in the left ventricular outflow tract velocity-time integral ≥10% defined FR. Results: Among 63 patients, 38 (60.3%) presented FR. The vCVP-ns was not significantly different between responders and nonresponders (−4.9 mm Hg [−7.5 to −3.1] vs. −4.1 mm Hg [−5.4 to 2.8], respectively; P = 0.15). The vCVP-st was lower in responders than nonresponders (−9.7 mm Hg [−13.9 to −6.2] vs. −3.6 mm Hg [−10.6 to −1.6], respectively; P = 0.004). A vCVP-st < −4.7 mm Hg predicted FR with 89.5% sensitivity, a specificity of 56.0%, and an area under the receiver operating characteristic curve of 0.72 (95% CI, 0.58 to 0.86) (P = 0.004). Conclusion: When a central venous catheter is present, elevated values for vCVP-st may be useful to identify spontaneously breathing patients unresponsive to volume expansion. Nevertheless, the necessity of performing a standardized, deep-inspiration maneuver may limit its clinical application.
Evaluation of CYFRA 21-1, Angiopoetin-2, Pentraxin-3, sRAGE, IL-6 and IL-10 in polytraumatized patients with concomitant thoracic trauma - helpful markers to predict pneumonia?
Authors: Vollrath Jan Tilmann , Schindler Cora Rebecca , Herrmann Eva , Verboket René D. , Henrich Dirk , Marzi Ingo , Störmann Philipp
Published: August 2023

Background

Pneumonia is a frequent complication after polytrauma. This study aims to evaluate the ability of different serum markers to identify patients at risk of developing pneumonia after polytrauma.

Methods

A retrospective analysis of prospectively collected data in polytraumatized patients with concomitant thoracic trauma (ISS ≥16, AISThorax ≥ 3) was performed. The study cohort was divided into patients with and without pneumonia during the clinical course. Serum levels of lung epithelial (CYFRA 21-1), endothelial (Ang-2) and inflammatory (PTX-3, sRAGE, IL-6, IL-10) markers were measured upon arrival in the trauma room and on days two and five.

Results

A total of 73 patients and 16 healthy controls were included in this study. Of these, 20 patients (27.4%) developed pneumonia. Polytraumatized patients showed significantly increased CYFRA 21-1 levels with a distinct peak after admission compared to healthy controls. Serum PTX-3 significantly increased on day two in polytraumatized patients compared to healthy controls. ISS and demographic parameters were comparable between both groups (pneumonia vs. no pneumonia). No statistically significant difference could be observed for serum levels of CYFRA 21-1, Ang-2, PTX-3, sRAGE, IL-6 and IL-10 between the groups (pneumonia vs. no pneumonia) on all days. Logistic regression revealed a combination of IL-6, IL-10, sRAGE and PTX-3 to be eventually helpful to identify patients at risk of developing pneumonia and our newly developed score was significantly higher on day 0 in patients developing pneumonia (p < 0.05).

Conclusion

The investigated serum markers alone are not helpful to identify polytraumatized patients at risk of developing pneumonia, whilst a combination of IL-6, IL-10, PTX-3 and sRAGE might be.
Predicting Cirrhosis and Poor Outcomes of Bile Drainage Surgery for Biliary Atresia
Authors: Tomita Hirofumi , Shimojima Naoki , Sasaki Hideyuki , Shimotakahara Akihiro , Yamada Yohei , Kuroda Tatsuo , Nio Masaki , Hirobe Seiichi
Published: August 2023

Objective:

To identify patients with biliary atresia (BA) with extremely poor outcomes of bile drainage surgery using the infant BA liver fibrosis (iBALF) score, a liver fibrosis marker based on standard blood analysis.

Summary Background Data:

Although primary liver transplantation (LTx) is beginning to be considered as an alternative to bile drainage surgery in patients with BA, those most likely to benefit from this procedure have not yet been identified.

Methods:

The medical records of 380 patients with BA with bile drainage surgery between 2015 and 2019 were collected for retrospective analysis from 60 participating hospitals. To predict native liver survival at age 1 year, a receiver-operating characteristic curve was drawn for the iBALF score. The cutoff value was determined as the point indicating >99% sensitivity.

Results:

The median age at surgery was 56 days (range: 4–183 d), and native liver survival at age 1 year was achieved in 258 (67.9%) patients. An iBALF score of 5.27 was chosen as the cutoff, and 18 patients (4.7%) were found to have an iBALF score >5.27; of these, only two (95% confidence interval [CI]: 1.4–34.7%) had native liver survival at age 1 year, indicating a significantly poorer outcome than in the other patients (95% CI: 65.7–75.4%). Moreover, patients with an iBALF score >5.27 had significantly higher mortality and younger age at salvage LTx.

Conclusions:

Patients with BA having a preoperative iBALF score >5.27 had extremely poor outcomes of bile drainage surgery and may be considered as candidates for primary LTx.
Multisensory decisions from self to world
Authors: Zaidel Adam , Salomon Roy
Published: August 2023

Classic Bayesian models of perceptual inference describe how an ideal observer would integrate ‘unisensory’ measurements (multisensory integration) and attribute sensory signals to their origin(s) (causal inference). However, in the brain, sensory signals are always received in the context of a multisensory bodily state—namely, in combination with other senses. Moreover, sensory signals from both interoceptive sensing of one's own body and exteroceptive sensing of the world are highly interdependent and never occur in isolation. Thus, the observer must fundamentally determine whether each sensory observation is from an external (versus internal, self-generated) source to even be considered for integration. Critically, solving this primary causal inference problem requires knowledge of multisensory and sensorimotor dependencies. Thus, multisensory processing is needed to separate sensory signals. These multisensory processes enable us to simultaneously form a sense of self and form distinct perceptual decisions about the external world. In this opinion paper, we review and discuss the similarities and distinctions between multisensory decisions underlying the sense of self and those directed at acquiring information about the world. We call attention to the fact that heterogeneous multisensory processes take place all along the neural hierarchy (even in forming ‘unisensory’ observations) and argue that more integration of these aspects, in theory and experiment, is required to obtain a more comprehensive understanding of multisensory brain function.

This article is part of the theme issue ‘Decision and control processes in multisensory perception’.
Crossmodal visual predictions elicit spatially specific early visual cortex activity but later than real visual stimuli
Authors: Stange Liesa , Ossandón José P. , Röder Brigitte
Published: August 2023

Previous studies have indicated that crossmodal visual predictions are instrumental in controlling early visual cortex activity. The exact time course and spatial precision of such crossmodal top-down influences on the visual cortex have been unknown. In the present study, participants were exposed to audiovisual combinations comprising one of two sounds and a Gabor patch either in the top left or in the bottom right visual field. Event-related potentials (ERPs) were recorded to these frequent crossmodal combinations (standards) as well as to trials in which the visual stimulus was omitted (omissions) or the visual and auditory stimuli were recombined (deviants). Standards and deviants elicited an ERP between 50 and 100 ms of opposite polarity known as the C1 effect commonly associated with retinotopic processing in early visual cortex. By contrast, a C1 effect was not observed in omission trials. Spatially specific omission and mismatch effects (deviants minus standards) started only later with a latency of 230 ms and 170 ms, respectively. These results suggest that crossmodal visual predictions control visual cortex activity in a spatially specific manner. However, visual predictions do not modulate visual cortex activity with the same timing as visual stimulation activates these areas but rather seem to involve distinct neural mechanisms.

This article is part of the theme issue ‘Decision and control processes in multisensory perception’.
Multisensory interactions of face and vocal information during perception and memory in ventrolateral prefrontal cortex
Authors: Romanski Lizabeth M. , Sharma Keshov K.
Published: August 2023

The ventral frontal lobe is a critical node in the circuit that underlies communication, a multisensory process where sensory features of faces and vocalizations come together. The neural basis of face and vocal integration is a topic of great importance since the integration of multiple sensory signals is essential for the decisions that govern our social interactions. Investigations have shown that the macaque ventrolateral prefrontal cortex (VLPFC), a proposed homologue of the human inferior frontal gyrus, is involved in the processing, integration and remembering of audiovisual signals. Single neurons in VLPFC encode and integrate species-specific faces and corresponding vocalizations. During working memory, VLPFC neurons maintain face and vocal information online and exhibit selective activity for face and vocal stimuli. Population analyses indicate that identity, a critical feature of social stimuli, is encoded by VLPFC neurons and dictates the structure of dynamic population activity in the VLPFC during the perception of vocalizations and their corresponding facial expressions. These studies suggest that VLPFC may play a primary role in integrating face and vocal stimuli with contextual information, in order to support decision making during social communication.

This article is part of the theme issue ‘Decision and control processes in multisensory perception’.
Metacognitive awareness in the sound-induced flash illusion
Authors: Maynes Randolph , Faulkner Ryan , Callahan Grace , Mims Callie E. , Ranjan Saurabh , Stalzer Justine , Odegaard Brian
Published: August 2023

Hundreds (if not thousands) of multisensory studies provide evidence that the human brain can integrate temporally and spatially discrepant stimuli from distinct modalities into a singular event. This process of multisensory integration is usually portrayed in the scientific literature as contributing to our integrated, coherent perceptual reality. However, missing from this account is an answer to a simple question: how do confidence judgements compare between multisensory information that is integrated across multiple sources, and multisensory information that comes from a single, congruent source in the environment? In this paper, we use the sound-induced flash illusion to investigate if confidence judgements are similar across multisensory conditions when the numbers of auditory and visual events are the same, and the numbers of auditory and visual events are different. Results showed that congruent audiovisual stimuli produced higher confidence than incongruent audiovisual stimuli, even when the perceptual report was matched across the two conditions. Integrating these behavioural findings with recent neuroimaging and theoretical work, we discuss the role that prefrontal cortex may play in metacognition, multisensory causal inference and sensory source monitoring in general.

This article is part of the theme issue ‘Decision and control processes in multisensory perception’.
Genomics of Acinetobacter baumannii iron uptake
Authors: Artuso Irene , Poddar Harsh , Evans Benjamin A. , Visca Paolo
Published: August 2023

Iron is essential for growth in most bacteria due to its redox activity and its role in essential metabolic reactions; it is a cofactor for many bacterial enzymes. The bacterium

Acinetobacter baumannii

is a multidrug-resistant nosocomial pathogen.

A. baumannii

responds to low iron availability imposed by the host through the exploitation of multiple iron-acquisition strategies, which are likely to deliver iron to the cell under a variety of environmental conditions, including human and animal infection. To date, six different gene clusters for active iron uptake have been described in

A. baumannii

, encoding protein systems involved in (i) ferrous iron uptake (feo); (ii) haem uptake (hemT and hemO); and (iii) synthesis and transport of the baumannoferrin(s) (bfn), acinetobactin (bas/bau) and fimsbactin(s) (fbs) siderophores. Here we describe the structure, distribution and phylogeny of iron-uptake gene clusters among >1000 genotypically diverse

A. baumannii

isolates, showing that feo, hemT, bfn and bas/bau clusters are very prevalent across the dataset, whereas the additional haem-uptake system hemO is only present in a portion of the dataset and the fbs gene cluster is very rare. Since the expression of multiple iron-uptake clusters can be linked to virulence, the presence of the additional haem-uptake system hemO may have contributed to the success of some

A. baumannii

clones.
Device-measured physical activity type, posture, and cardiometabolic health markers: pooled dose-response associations from the ProPASS Consortium
Authors: Ahmadi Matthew N. , Blodgett Joanna M , Atkin Andrew J , Chan Hsiu-Wen , del Pozo Cruz Borja , Suorsa Kristin , Bakker Esmee A , Pulsford Richard M , Mielke Gregore I , Johansson Peter J. , Hettiarachchi Pasan , Thijssen Dick H.J. , Stenholm Sari , Mishra Gita D , Teixeira-Pinot Armando , Rangul Vegar , Sherar Lauren B , Ekelund Ulf , Hughes Alun D. , Lee I-Min ,   ProPASS collaboration, Holtermann Andreas , Koster Annemarie , Hamer Mark , Stamatakis Emmanuel
Published: August 2023

Aims/hypothesis

To examine the dose-response associations between device-measured physical activity types and posture (sitting and standing time) with cardiometabolic health.

Methods

An individual participant harmonised meta-analysis of 12,095 adults (mean age±SD= 54.5±9.6 years; Female=54.8%) from 6 cohorts with thigh-worn accelerometry. Associations of average daily duration of walking, stair climbing, running, standing and sitting with composite cardiometabolic health score (based on standardised z-scores) and individual cardiometabolic markers (body mass index, waist circumference, triglycerides, high-density lipoprotein cholesterol, glycated haemoglobin, and total cholesterol) were examined cross-sectionally using generalised linear modelling and cubic splines.

Results

We observed more favourable composite cardiometabolic health (i.e. z-score <0) at approximately 64 minutes/day walking (z-score [95%CI] = -0.14 [-0.25, - 0.02]) and 5 minutes/day stair climbing (-0.14 [-0.24, -0.03]). We observed an equivalent magnitude of association at 2.6 hours/day standing. Any amount of running was associated with better composite cardiometabolic health. We did not observe an upper limit to the magnitude of the dose-response associations for any activity type or standing. There was an inverse dose-response association between sitting time and composite cardiometabolic health that became markedly less favourable when daily durations exceeded 12.1 hours/day. Associations for sitting time were no longer significant after excluding participants with prevalent cardiovascular disease or medication use. The dose-response pattern was generally consistent between activity and posture types and individual cardiometabolic health markers.

Conclusions/interpretation

In the first activity-type specific analysis of device-based physical activity, ∼64 minutes/day of walking and ∼5.0 minutes/day of stair climbing, was associated with a favourable cardiometabolic risk profile. The deleterious associations of sitting time were fully attenuated after exclusion of participants with prevalent cardiovascular disease and medication use. Our findings on cardiometabolic health and durations in different activity-types and posture may inform clinicians and future interventions to provide personalised prescription options.
Exploration of Short-range Neonatal Seizure Forecasting with Quantitative EEG Based Deep Learning
Authors: Kim Jonathan , Glass Hannah C , Amorim Edilberto , Rao Vikram R , Bernardo Danilo
Published: August 2023

Background

In this study, we utilize robust feature selection of quantitative encephalography (QEEG) features for inclusion into a deep learning (DL) model for short-range forecasting of neonatal seizure risk.

Methods

We used publicly available EEG seizure datasets with a total of 132 neonates. The Boruta algorithm with Shapley values was used for QEEG feature selection into a convolutional long short-term memory (ConvLSTM) DL model to classify preictal versus interictal states. ConvLSTM was trained and evaluated with 10-fold cross-validation. Performance was evaluated with varying seizure prediction horizons (SPH) and seizure occurrence periods (SOP).

Results

Boruta with Shapley values identified statistical moments, spectral power distributions, and RQA features as robust predictors of preictal states. ConvLSTM performed best with SPH 3 min and SOP 7 min, demonstrating 80% sensitivity with 36% of time spent in false alarm, AUROC of 0.80, and AUPRC of 0.23. The model demonstrated ECE of 0.106, consistent with moderate calibration. Evaluation of forecasting skill with BSS under varying SPH demonstrated a peak BSS of 0.056 and a trend for decreasing BSS with increasing SPH.

Conclusion

Statistical moments, spectral power, and recurrence quantitative analysis are predictive of the preictal state. Short-range neonatal seizure forecasting is feasible with DL models utilizing these features.
Protein aggregation of DISC1, as assayed by insolubility, varies across the brain of an individual with schizophrenia and Alzheimer’s disease
Authors: Samardžija Bobana , Renner Éva , Palkovits Miklós , Bradshaw Nicholas J.
Published: August 2023

Objective

Subgroups of mental illness patients have been seen to display disturbed proteostasis, with specific proteins aggregating in their brain, which is generally determined by assaying protein insolubility in thepost mortemsamples. Such studies typically only look at one region of the brain, and therefore we aimed to determine the distribution of protein across a single brain, using this insolubility-based approach.

Methods

We looked at 20 postmortemtissue samples from across the brain of a single patient, with schizophrenia and Alzheimer’s disease, determined which protein(s) aggregated in his brain relative to controls, based on purification of insoluble protein fractions. The individual samples were then similarly analysed.

Results

Disrupted in Schizophrenia 1 (DISC1) protein was seen to be insoluble in the patient’s brain, however in a very heterogenous picture, with differences in insoluble DISC1 even between samples of the same region, but opposite hemispheres.

Conclusions

While caution must be taken in extrapolating from a single individual, this raises the possibility that aggregates of DISC1 may spread throughout the brain, as is the case for proteins in neurodegenerative disorders, and suggests that current studies looking at single brain regions may be underestimating the prevalence of protein aggregates in schizophrenia.
The effect of conflict on medical facilities in Mariupol, Ukraine: a quasi-experimental study
Authors: Poole Danielle N. , Andersen Daniel , Raymond Nathaniel A. , Parham Jack , Howarth Caitlin , Hathaway Oona A. , Khoshnood Kaveh ,   Yale Humanitarian Research Lab
Published: August 2023

Medical facilities are civilian objects specially protected by international humanitarian law. Despite the need for systematic documentation of the effects of war on medical facilities for judiciary accountability, current methods for surveilling damage to protected civilian objects during ongoing armed conflict are insufficient. Satellite imagery damage assessment confers significant possibilities for investigating patterns of war. We leveraged commercially and publicly available satellite imagery and geolocated facility data to conduct a pre-post quasi-experimental study of damage to medical infrastructure in Mariupol, Ukraine as a result of Russia’s invasion. We found that 77% of medical facilities in Mariupol sustained damage during Russia’s siege lasting from February 24 - May 20, 2022. Facility size was not associated with damage, suggesting that attacks on medical facilities are not a residual of physical infrastructure characteristics. This is the first geographically comprehensive pre-post study of the effects of an ongoing conflict on specially protected medical infrastructure.
The post-COVID-19 population has a high prevalence of crossreactive antibodies to spikes from allOrthocoronavirinaegenera
Authors: Singh Gagandeep , Abbad Anass , Kleiner Giulio , Srivastava Komal , Gleason Charles ,   PARIS Study Group, Carreño Juan Manuel , Simon Viviana , Krammer Florian
Published: August 2023

The Orthocoronaviridae subfamily is large comprising four highly divergent genera. Four seasonal coronaviruses were circulating in humans prior to the coronavirus disease 2019 (COVID-19) pandemic. Infection with these viruses induced antibody responses that are relatively narrow with little cross-reactivity to spike proteins of other coronaviruses. Here, we report that infection with and vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces broadly crossreactive binding antibodies to spikes from a wide range of coronaviruses including members of the sarbecovirus subgenus, betacoronaviruses including Middle Eastern respiratory syndrome coronavirus (MERS CoV), and extending to alpha-, gamma- and delta-coronavirus spikes. These data show that the coronavirus spike antibody landscape in humans has profoundly been changed and broadened as a result of the SARS-CoV-2 pandemic. While we do not understand the functionality of these crossreactive antibodies, they may lead to enhanced resistance of the population to infection with newly emerging coronaviruses with pandemic potential.
Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses than that of the Partially Effective gB/MF59 Vaccine
Authors: Hu Xintao , Karthigeyan Krithika P. , Herbek Savannah , Valencia Sarah M. , Jenks Jennifer A. , Webster Helen , Miller Itzayana G. , Connors Megan , Pollara Justin , Andy Caroline , Gerber Linda M. , Walter Emmanuel B. , Edwards Kathryn M. , Bernstein David I. , Hou Jacob , Koch Matthew , Panther Lori , Carfi Andrea , Wu Kai , Permar Sallie R.
Published: August 2023

Background

The MF59-adjuvanted gB subunit (gB/MF59) vaccine demonstrated ~50% efficacy against human cytomegalovirus (HCMV) acquisition in multiple clinical trials, suggesting efforts to improve this vaccine design might yield a vaccine suitable for licensure. A vaccine candidate employing nucleoside-modified mRNAs encoding HCMV gB and pentameric complex (PC) encapsulated in lipid nanoparticle, mRNA-1647, is currently in late-stage efficacy trials. Yet, its immunogenicity has not been compared to the partially-effective gB/MF59 vaccine.

Methods

We assessed neutralizing and Fc-mediated IgG effector antibody responses induced by mRNA-1647, a vaccine comprising an equal mass of 6 mRNAs encoding gB and PC antigens, in both HCMV seropositive and seronegative vaccinees from a first-in-human clinical trial through 1-year following 3rdvaccination using a systems serology approach. Further, we compared peak anti-gB antibody responses in seronegative mRNA-1647 vaccinees to that of seronegative female adolescent gB/MF59 vaccine recipients.

Results

mRNA-1647 vaccination boosted pre-existing HCMV-specific IgG responses in seropositive vaccinees, including neutralizing and Fc-mediated effector antibody responses. In seronegative vaccinees, mRNA-1647 induced durable and functional HCMV-specific IgG responses. Elicited gB-specific IgG responses were lower than the PC-specific IgG responses. Additionally, gB-specific IgG and antibody-dependent cellular phagocytosis (ADCP) responses were lower than those elicited by gB/MF59. However, mRNA-1647 elicited robust neutralization and high antibody-dependent cellular cytotoxicity (ADCC) responses.

Conclusions

mRNA-1647 vaccination induced polyfunctional and durable HCMV-specific antibody responses. mRNA-1647-elicited gB-specific IgG responses were lower than PC-specific IgG responses and lower than those elicited by the partially effective gB/MF59. However, higher neutralization and ADCC responses were elicited by mRNA-1647 than gB/MF59.

Clinical Trials Registration

ClinicalTrials.gov(NCT03382405, mRNA-1647) and (NCT00133497, gB/MF59).

mRNA-1647 HCMV vaccine elicited polyfunctional and durable antibody responses in humans. While the mRNA-1647-elicited glycoprotein B (gB)-specific IgG responses were lower than that of the moderately-effective gB/MF59 vaccine, the pentameric complex (PC)-specific IgG responses were strong.
COVID pandemic impact on hypertension management in North-East London: an observational cohort study using electronic health records
Authors: Rison Stuart CG , Redfern Oliver , Mathur Rohini , Dostal Isabel , Carvalho Chris , Raisi-Estabragh Zahra , Robson John P
Published: August 2023

Background

The COVID19 pandemic had a major impact on primary care management of long-term conditions such as hypertension. This observational cohort study of adults with hypertension registered in 193 primary care practices in North-East London between January 2019 and October 2022 investigated the impact of the COVID19 pandemic on the treatment and control of blood pressure including demographic and social inequities.

Method and findings

In 224,329 adults with hypertension, the proportion with a blood pressure (BP) recorded within the preceding 1 year fell from a 91% pre-pandemic peak to 62% at the end of the pandemic lock-down phase and improved to 77% by the end of the study. The proportion with controlled hypertension (<80 years old, BP ≤140/90mmHg; 80 or more years old: ≤150/90mmHg) for the same time points was 81%, 50% and 60% respectively. Using ‘blood pressure control’ (which considered only patients with a valid blood pressure recording) as the indicator attenuated the reduction to 83%, 80% and 78% respectively.

The study used multivariable logistic analysis at four representative time points (Pre-pandemic: April 2019; Pre lockdown: April 2020; Lockdown: April 2021; Post-lockdown: April 2022) to identify temporal, clinical and demographic influences on blood pressure monitoring and control.

Pre-pandemic inequities in the management of hypertension were not significantly altered by the pandemic. Throughout the pandemic phases, in comparison to the White ethnic group, the Black ethnic group was less likely to achieve blood pressure control (ORs 0.81 [95% CI = 0.78 to 0.85, p-value<0.001] to 0.87 [95% CI = 0.84 to 0.91, p-value<0.001]). Conversely, the Asian ethnic group was more likely to have controlled blood pressure (ORs 1.09 [95% CI = 1.05 to 1.14, p-value<0.001] to 1.28 [95% CI = 1.23 to 1.32, p-value<0.001]). Younger, male, more affluent individuals, individuals with unknown or unrecorded ethnicity or those untreated were less likely to have blood pressure controlled to target throughout the study.

Conclusion

The COVID pandemic had a greater impact on blood pressure recording than on blood pressure control. Although recording and control have improved, these had not returned to pre-pandemic levels by the end of the study period. Ethnic inequalities in blood pressure control persisted during the pandemic and remain outstanding.
Resident memory T cell precursors in tumor draining lymph nodes require type-1 IFN for optimal differentiation
Authors: Khatwani Nikhil , Searles Tyler , Han Jichang , Messier Cameron , Mittal Neeti , Hawkes Aaron , Molodstov Aleksey K. , Ramirez Delaney E. , Wilkins Owen , Huang Yina H. , Kolling Fred W. , Rosato Pamela C , Turk Mary Jo
Published: August 2023

Resident memory (Trm) cells play an essential role in anti-tumor immunity. However, little is known about the precursors that differentiate into protective Trm populations against cancer. Here we employed an established model of B16 melanoma neoadjuvant anti-CD4 therapy, to track tumor antigen-specific CD8+ T cells through tissues and across time; from their priming as effectors to their differentiation into Trm. We show that tumor-draining lymph nodes (TDLNs) contain Teff cells that begin to express canonical Trm markers CD103 and CD69. These tumor-specific Teff cells seeded skin and tumor during the effector phase of the response, although egress from these tissues was not required Trm development in LNs. Paired scRNAseq/scTCRseq was used to identify Teff clonotypes in TDLNs and trace their differentiation, in real-time, into Trm populations. We found that expanded clonotypes favored the Trm fate and were unlikely to co-differentiate into other lineages. Precursors of Trm (pre-Trm) clonotypes that subsequently seeded populations throughout tumors, LNs, and skin, were characterized by early expression of tissue residency, stemness, and type-1 IFN sensing genes. These multipotent pre-Trm cells sensed plasmacytoid dendritic cell-derived type-1 interferons in TDLNs, and their expression of interferon alpha receptor was required for their formation of Trm populations in LNs but not in skin. These findings reveal the defining features of pre-Trm cells in response to tumor antigens, and reveal a previously unappreciated role for type-1 IFNs in programming regional Trm immunity to cancer.

One Sentence Summary

Anti-tumor effector CD8 T cells adopt early characteristics of tissue residency and stemness, and rely on the sensing of type-1 interferons for their local differentiation into resident memory T cells.