bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicles containing the I‐BAR protein IRSp53 are released from the cell plasma membrane in an Arp2/3 dependent manner
Authors: de Poret Aurore , Dibsy Rayane , Merida Peggy , Trausch Alice , Inamdar Kaushik , Muriaux Delphine
Published: July 2022

Backgroud

Extracellular vesicles (EVs) are nanometric membrane vesicles produced by cells and involved in cell–cell communication. EV formation can occur in endosomal compartments whose budding depends on the ESCRT machinery (i.e., exosomes), or at the cell plasma membrane (i.e., EVs or microvesicles). How these EVs bud from the cell plasma membrane is not completely understood. Membrane curvatures of the plasma membrane toward the exterior are often generated by I‐BAR domain proteins. I‐BAR proteins are cytosolic proteins that when activated bind to the cell plasma membrane and are involved in protrusion formation including filopodia and lamellipodia. These proteins contain a conserved I‐BAR domain that senses curvature and induces negative membrane curvatures at the plasma membrane. I‐BAR proteins, such as IRSp53, also interact with actin co‐factors to favor membrane protrusions.

Results

Here, we explore whether the I‐BAR protein IRSp53 is sorting with EVs and if ectopic GFP‐tagged I‐BAR proteins, such as IRSp53‐GFP, as well as related IRTKS‐GFP or Pinkbar proteins, can be found in these EVs originated from the cell plasma membrane. We found that a subpopulation of these I‐BAR EVs, which are negative for the CD81 exosomal biomarker, are produced from the cell plasma membrane in a TSG101‐independent manner but in an Arp2/3‐dependent manner.

Conclusions

Our results thus reveal that IRSp53 containing EVs represent a subset of plasma membrane EVs whose production depends on branched actin.

Significance

IRSp53 belongs to the I‐BAR family proteins involved in curving cell membranes through a link with cortical actin. In that perspective, IRSp53 was shown to help membrane curvature of HIV‐1 particles and, here, to be part of the budding process of a sub‐population of EVs through its link with Arp2/3. IRSp53 is consequently a biomarker of these EVs of the cell plasma membrane.
Tumor microenvironmental 15‐PGDH depletion promotes fibrotic tumor formation and angiogenesis in pancreatic cancer
Authors: Bu Luke , Yonemura Atsuko , Yasuda‐Yoshihara Noriko , Uchihara Tomoyuki , Ismagulov Galym , Takasugi Sanae , Yasuda Tadahito , Okamoto Yuya , Kitamura Fumimasa , Akiyama Takahiko , Arima Kota , Itoyama Rumi , Zhang Jun , Fu Lingfeng , Hu Xichen , Wei Feng , Arima Yuichiro , Moroishi Toshiro , Nishiyama Koichi , Sheng Guojun , Mukunoki Toshifumi , Otani Jun , Baba Hideo , Ishimoto Takatsugu
Published: July 2022

The arachidonic acid cascade is a major inflammatory pathway that produces prostaglandin E2 (PGE2). Although inhibition of 15‐hydroxyprostaglandin dehydrogenase (15‐PGDH) is reported to lead to PGE2 accumulation, the role of 15‐PGDH expression in the tumor microenvironment remains unclear. We utilized Panc02 murine pancreatic cancer cells for orthotopic transplantation into wild‐type and 15‐pgdh+/− mice and found that 15‐pgdh depletion in the tumor microenvironment leads to enhanced tumorigenesis accompanied by an increase in cancer‐associated fibroblasts (CAFs) and the promotion of fibrosis. The fibrotic tumor microenvironment is widely considered to be hypovascular; however, we found that the angiogenesis level is maintained in 15‐pgdh+/− mice, and these changes were also observed in a genetically engineered PDAC mouse model. Further confirmation revealed that fibroblast growth factor 1 (FGF1) is secreted by pancreatic cancer cells after PGE2 stimulation, consequently promoting CAF proliferation and vascular endothelial growth factor A (VEGFA) expression in the tumor microenvironment. Finally, in 15‐pgdh+/−Acta2‐TK mice, depletion of fibroblasts inhibited angiogenesis and cancer cell viability in orthotopically transplanted tumors. These findings highlighted the role of 15‐pgdh downregulation in enhancing PGE2 accumulation in the pancreatic tumor microenvironment and in subsequently maintaining the angiogenesis level in fibrotic tumors along with CAF expansion.
Circulating cancer‐associated extracellular vesicles as early detection and recurrence biomarkers for pancreatic cancer
Authors: Yoshioka Yusuke , Shimomura Manami , Saito Keigo , Ishii Hideshi , Doki Yuichiro , Eguchi Hidetoshi , Nakatsura Tetsuya , Itoi Takao , Kuroda Masahiko , Mori Masaki , Ochiya Takahiro
Published: July 2022

Early detection of pancreatic ductal adenocarcinoma (PDAC) is essential for improving patient survival rates, and noninvasive biomarkers are urgently required to identify patients who are eligible for curative surgery. Here, we examined extracellular vesicles (EVs) from the serum of PDAC patients to determine their ability to detect early‐stage disease. EV‐associated proteins purified by ultracentrifugation and affinity columns underwent proteomic analysis to identify novel PDAC markers G protein‐coupled receptor class C group 5 member C (GPRC5C) and epidermal growth factor receptor pathway substrate 8 (EPS8). To verify the potency of GPRC5C‐ or EPS8‐positive EVs as PDAC biomarkers, we analyzed EVs from PDAC patient blood samples using ultracentrifugation in two different cohorts (a total of 54 PDAC patients, 32 healthy donors, and 22 pancreatitis patients) by immunoblotting. The combination of EV‐associated GPRC5C and EPS8 had high accuracy, with area under the curve values of 0.922 and 0.946 for distinguishing early‐stage PDAC patients from healthy controls in the two cohorts, respectively, and could detect PDAC patients who were negative for CA19‐9. Moreover, we analyzed 30 samples taken at three time points from 10 PDAC patients who underwent surgery: before surgery, after surgery, and recurrence as an early‐stage model. These proteins were detected in EVs derived from preoperative and recurrence samples. These results indicated that GPRC5C‐ or EPS8‐positive EVs were biomarkers that have the potential to detect stage I early pancreatic cancer and small recurrent tumors detected by computed tomography.
The attitudes and beliefs of the child protection workforce and why they matter to children who live with violence
Authors: Alexander Kate , Humphreys Cathy , Wise Sarah , Zhou Albert
Published: July 2022

In Australia, like other developed countries, there has been an increase in reports to child protection services about children experiencing domestic violence. While there is research on the importance of the skills and knowledge of the child protection workforce for this growing problem, little is available about practitioner attitudes and beliefs. This paper presents findings on research undertaken in New South Wales, which is the most populated state in Australia. The research considered the attitudes and beliefs of the statutory child protection workforce about domestic violence. It relied on a large‐scale survey of 1041 child protection practitioners. In order to compare the attitudes and beliefs of child protection workforce with those of the general community, the survey replicated questions from the Australian National Community Attitudes towards Violence against Women Surveys. Overall, the attitudes and beliefs of the workforce more closely reflected contemporary theory and evidence about domestic violence than those of the community. The research also examined variations in the attitudes and beliefs of the child protection workforce according to practitioner characteristics, finding variations by gender. The implications for the fields of child protection and social work are discussed.
Cardiac remodelling in association with left ventricular dyssynchrony and systolic dysfunction in patients with coronary artery disease
Authors: Hämäläinen Hanna , Laitinen Tiina M. , Hedman Marja , Hedman Antti , Kivelä Antti , Laitinen Tomi P.
Published: July 2022

Background

In patients with coronary artery disease (CAD), ischaemic cardiomyopathy may result in progressive cardiac remodelling and left ventricular (LV) dysfunction. Myocardial perfusion imaging (MPI) can be used to quantify LV size and shape, mechanical dyssynchrony (LVMD) and ejection fraction (EF) as well as myocardial ischaemia and injury extents. We investigated the prevalence of LV remodelling (LVR) in patients with CAD and the relationship between LVR, LVMD and EF.

Methods

Three hundred twenty‐six patients with CAD were evaluated. The EF and end‐diastolic volume (EDV) were measured using MPI. LVMD was assessed using phase analysis. LVR was characterised according to LV dilatation or increased shape indices (systolic shape index [SIES] and diastolic shape index [SIED]).

Results

LVR were observed in 41% of CAD patients. EDV, SIES and SIED were larger in patients with LVMD or low EF. After adjustment for age, sex and infarct and ischaemia extents, phase histogram bandwidth correlated with EDV (r = 0.218) and SIES (r = 0.266) and EF correlated with EDV (r = –0.535), SIES (r = –0.554) and SIED (r = –0.217, p < 0.001 for all).

Conclusions

LVR is frequently seen in patients with CAD and may be detected even before the development of symptomatic heart failure. A large LV volume and a more spherical‐shaped LV were associated with LVMD and low EF, highlighting the close relationships between remodelling and systolic dyssynchrony and dysfunction. MPI is useful for assessing LVR by providing information about LV size and shape, which changes from an ellipsoid towards a spherical form in the development of ischaemic cardiomyopathy.
In kidney recipients from the same deceased donor, discordance in delayed graft function is associated with the worst outcomes
Authors: Yousif Elsadig A. I. , Muth Brenda , Manchala Venkata , Turk Jennifer , Blazel Justin , Bloom Margaret , Garg Neetika , Aziz Fahad , Mohamed Maha , Djamali Arjang , Mandelbrot Didier , Parajuli Sandesh
Published: July 2022

Introduction

Delayed graft function (DGF) is a common complication among deceased donor kidney transplant recipients (DDKTs) and is associated with worse outcomes. The effect on outcomes of concordance versus discordance in DGF between two different recipients of kidneys from the same donor is largely unknown.

Methods

We reviewed all adult DDKTs for which both kidneys were transplanted to two different recipients at our center between 2014–2019. DDKTs were divided into four groups based on the DGF status: concordance no DGF (cc‐no‐DGF); discordance no DGF(dd‐no‐DGF); discordance DGF (dd‐DGF) and concordance in DGF (cc‐DGF). Acute rejection (AR) and death censored graft failure (DCGF) were outcomes of interest.

Results

A total of 578 DDKTs fulfilled our selection criteria, 280were in cc‐no‐DGF, 83 in dd‐no‐DGF, 83 in dd‐DGF, and 132 in cc‐DGF. Compared to cc‐no‐DGF, in univariate analysis, dd‐DGF was associated with an increased risk of AR (HR: 1.60; 95% CI: 1.0‐2.56) but cc‐DGF was not (HR: 1.01; 95% CI: 0.63‐1.62). dd‐DGF was not associated with an increased risk of AR in multivariate analysis. In multivariate analysis, dd‐DGF was associated with an increased risk of DCGF (HR: 2.70; 95% CI: 1.05‐6.93) but cc‐DGFwas not (HR: 2.36; 95% CI: 0.97‐5.70).

Conclusion

Discordance in DGF is associated with worse outcomes and may need closefollow‐up and monitoring to improve the outcomes.
Quantifying and reporting outcome measures in pediatric epilepsy surgery: A systematic review
Authors: Chisolm Paul F. , Warner Jeffrey D. , Hale Andrew T. , Estevez‐Ordonez Dagoberto , Murdaugh Donna , Rozzelle Curtis J. , Blount Jeffrey P.
Published: July 2022

Several instruments and outcomes measures have been reported in pediatric patients undergoing epilepsy surgery. The objective of this systematic review is to summarize, evaluate, and quantify outcome metrics for the surgical treatment of pediatric epilepsy that address seizure frequency, neuropsychological, and health‐related quality of life (HRQL). We performed a systematic review according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines to identify publications between 2010 and June 2021 from PubMed, Embase, and the Cochrane Database of Systematic Reviews that report clinical outcomes in pediatric epilepsy surgery. Eighty‐one articles were included for review. Overall, rates of postoperative seizure frequency were the most common metric reported (n = 78 studies, 96%). Among the seizure frequency metrics, the Engel Epilepsy Surgery Outcome Scale (n = 48 studies, 59%) was most commonly reported. Neuropsychological outcomes, performed in 32 studies (40%) were assessed using 36 different named metrics. HRQL outcomes were performed in 16 studies (20%) using 13 different metrics. Forty‐six studies (57%) reported postoperative changes in antiepileptic drug (AED) regimen, and time‐to‐event analysis was performed in 15 (19%) studies. Only 13 outcomes metrics (1/5 seizure frequency, 6/13 HRQL, 6/36 neuropsychological) have been validated for use in pediatric patients with epilepsy and only 13 have been assessed through reliability studies (4/5 seizure frequency, 6/13 HRQL, and 3/36 neuropsychological). Of the 81 included studies, 17 (21%) used at least one validated metric. Outcome variable metrics in pediatric epilepsy surgery are highly variable. Although nearly all studies report seizure frequency, there is considerable variation in reporting. HRQL and neuropsychological outcomes are less frequently and much more heterogeneously reported. Reliable and validated outcomes metrics should be used to increase standardization and accuracy of reporting outcomes in pediatric patients undergoing epilepsy surgery.
Episodic memory network connectivity in temporal lobe epilepsy
Authors: Fleury Marine , Buck Sarah , Binding Lawrence P. , Caciagli Lorenzo , Vos Sjoerd B. , Winston Gavin P. , Thompson Pamela J. , Koepp Matthias J. , Duncan John S. , Sidhu Meneka K.
Published: July 2022

Objective

Temporal lobe epilepsy (TLE) affects brain networks and is associated with impairment of episodic memory. Temporal and extratemporal reorganization of memory functions is described in functional magnetic resonance imaging (fMRI) studies. Functional reorganizations have been shown at the local activation level, but network‐level alterations have been underinvestigated. We aim to investigate the functional anatomy of memory networks using memory fMRI and determine how this relates to memory function in TLE.

Methods

Ninety patients with unilateral TLE (43 left) and 29 controls performed a memory‐encoding fMRI paradigm of faces and words with subsequent out‐of‐scanner recognition test. Subsequent memory event‐related contrasts of words and faces remembered were generated. Psychophysiological interaction analysis investigated task‐associated changes in functional connectivity seeding from the mesial temporal lobes (MTLs). Correlations between changes in functional connectivity and clinical memory scores, epilepsy duration, age at epilepsy onset, and seizure frequency were investigated, and between connectivity supportive of better memory and disease burden. Connectivity differences between controls and TLE, and between TLE with and without hippocampal sclerosis, were explored using these confounds as regressors of no interest.

Results

Compared to controls, TLE patients showed widespread decreased connectivity between bilateral MTLs and frontal lobes, and increased local connectivity between the anterior MTLs bilaterally. Increased intrinsic connectivity within the bilateral MTLs correlated with better out‐of‐scanner memory performance in both left and right TLE. Longer epilepsy duration and higher seizure frequency were associated with decreased connectivity between bilateral MTLs and left/right orbitofrontal cortex (OFC) and insula, connections supportive of memory functions. TLE due to hippocampal sclerosis was associated with greater connectivity disruption within the MTL and extratemporally.

Significance

Connectivity analyses showed that TLE is associated with temporal and extratemporal memory network reorganization. Increased bilateral functional connectivity within the MTL and connectivity to OFC and insula are efficient, and are disrupted by greater disease burden.
Genetic parallelism between European flat oyster populations at the edge of their natural range
Authors: Lapègue Sylvie , Reisser Céline , Harrang Estelle , Heurtebise Serge , Bierne Nicolas
Published: July 2022

Although all marine ecosystems have experienced global‐scale losses, oyster reefs have shown the greatest. Therefore, substantial efforts have been dedicated to restoration of such ecosystems during the last two decades. In Europe, several pilot projects for the restoration of the native European flat oyster, Ostrea edulis, recently begun and recommendations to preserve genetic diversity and to conduct monitoring protocols have been made. In particular, an initial step is to test for genetic differentiation against homogeneity among the oyster populations potentially involved in such programs. Therefore, we conducted a new sampling of wild populations at the European scale and a new genetic analysis with 203 markers to (1) confirm and study in more detail the pattern of genetic differentiation between Atlantic and Mediterranean populations, (2) identify potential translocations that could be due to aquaculture practices and (3) investigate the populations at the fringe of the geographical range, since they seemed related despite their geographic distance. Such information should be useful to enlighten the choice of the animals to be translocated or reproduced in hatcheries for further restocking. After the confirmation of the general geographical pattern of genetic structure and the identification of one potential case of aquaculture transfer at a large scale, we were able to detect genomic islands of differentiation mainly in the form of two groups of linked markers, which could indicate the presence of polymorphic chromosomal rearrangements. Furthermore, we observed a tendency for these two islands and the most differentiated loci to show a parallel pattern of differentiation, grouping the North Sea populations with the Eastern Mediterranean and Black Sea populations, against geography. We discussed the hypothesis that this genetic parallelism could be the sign of a shared evolutionary history of the two groups of populations despite them being at the border of the distribution nowadays.
Examining target language proficiency among in‐service K‐12 language teachers
Authors: Bell Teresa R. , Borden Rebecca S.
Published: July 2022

Advanced oral proficiency is an integral part of language teacher education and has been for decades. To date, little research exists that investigates practicing K‐12 nonnative language teachers' target language (TL) maintenance habits. This study presents the results of a research study that investigated the TL proficiency maintenance practices outside the classroom and the current oral proficiency rating of 104 language teachers in Oklahoma and Utah. Data were collected by means of a questionnaire and an official ACTFL OPIc. Results indicate that the majority of current language teachers have either maintained or improved their level of TL proficiency from when they started teaching and that all teacher participants consciously use their TL outside of the classroom. These results have implications for language teacher preparation programs, district and state language supervisors, ACTFL, and CAEP.
The Spatiotemporal Evolution of Sydney's Tram Network Using Network Econometrics
Authors: Wang Yingshuo , Lahoorpoor Bahman , Levinson David M.
Published: July 2022

This paper examines the evolution of Sydney trams using network econometrics approaches. Network econometrics extends spatial econometrics by developing weight matrices based on the physical structure of the network, allowing for competing and complementary elements to have distinct effects. This research establishes a digitized database of Sydney historical tramway network, providing a complete set of geo‐referenced data of the opening and closing year and frequencies by time of day for every line. An autoregressive distributed lag model is specified and reveals that the combination of correlation strength and magnitude of lagged flow change on correlated links is a significant predictor of future tram service. The results indicate that complementary and competitive links play distinct roles in shaping the network structure. A link is more likely to undergo the same structural change highly complementary (upstream or downstream) links underwent previously, where the influence is measured by a combination of correlation strength and link importance, reflected by historical service levels.
Individualised prophylaxis based on personalised target trough FVIII level optimised clinical outcomes in paediatric patients with severe haemophilia A
Authors: Huang Kun , Ai Di , Li Gang , Zhen Yingzi , Wang Yan , Zhang Ningning , Huo Aihua , Liu Guoqing , Chen Zhenping , Wu Runhui
Published: July 2022

Introduction

As standard care of severe haemophilia A (SHA), prophylaxis should be individualised.

Aim

This study aimed to investigate the effectiveness of this new‐proposed individualised prophylaxis protocol.

Methods

Boys with SHA were enrolled and followed a PK‐guided, trough‐level escalating protocol of prophylaxis after a six‐month observational period. In the next 2 years, clinical assessments including joint bleeds, ultrasound (US) scores and Haemophilia Joint Health Score (HJHS) in both sides of ankles, knees and elbows were conducted every 6 months as a scoring system, which determined whether the trough level's escalation. Adjustment of dosing regimen was based on WAPPS‐Hemo.

Results

Fifty‐eight SHA boys were finally analysed. Their age and bodyweight were 5.3(2.8,6.9) years and 21.5(16,25) kg. During the study, 47 escalations were conducted. At study exit, the patient number and proportion of different trough level groups were: < 1 IU/dl, 17.2% (10/58); 1–3 IU/dl, 53.5% (31/58); 3–5 IU/dl, 15.5% (9/58); > 5 IU/dl, 13.8% (8/58). Significantly reduced annualised bleeding rate [4(0,8) to 0(0,2), p < .0001] and annualised joint bleeding rate [2(0,4) to 0(0,.25), p < .0001] was observed at study exit as well as the continuous trend of increased zero bleeding proportion (ZBP) (27.6%–69.0%) and zero joint bleeding proportion (46.5%–81.3%). Besides, 85% (6/7) of the target joints vanished. Statistical improvements of US scores (p = .04) and HJHS (p = .02) were also reported at study exit.

Conclusion

Our results showed the effectiveness of our protocol based on individualised target trough level and emphasise the importance of personalised prophylaxis.
Macroinvertebrate communities in high mountain desert wetlands: Building biological indexes to address the vulnerability of species and communities
Authors: Scheibler Erica Elizabeth , Montemayor Sara Itzel , Melo María Cecilia
Published: July 2022

Andean wetlands in arid climates are isolated ecosystems surrounded by steep terrain and have crucial relevance as a water resource. The species inhabiting them are adapted to these habitats and vulnerable to environmental changes.

The aim of this study is to evaluate the vulnerability of invertebrate aquatic species to climate change and organic pollution through an index adapted from the species distributional models (SDM) score [vulnerability of aquatic invertebrate species index (Vais)], and the vulnerability of the invertebrate communities through an index developed herein [wetland community vulnerability index (Wcv)].

The Vais index ranges from 1 (highly vulnerable) to 0 (non‐vulnerable species). It was calculated for 22 species of the orders Coleoptera, Ephemeroptera, Hemiptera, and Odonata. According to our results, the most vulnerable species belong to the orders Ephemeroptera (2) and Odonata (8) (scores 0.63–0.76); species with medium vulnerability belong to the orders Coleoptera (1) Ephemeroptera (1), Hemiptera (4) and Odonata (1) (scores 0.43–0.54); and the most tolerant species belong to the orders Coleoptera (2) and Hemiptera (3) (0.31–0.29).

The Wcv index was calculated for 31 communities in Andean wetlands. Lower Wcv values correspond to less vulnerable communities and higher values to more vulnerable communities. According to our results, communities can be divided into three groups: the most vulnerable (scores 0.61–0.71), the ones with medium vulnerability (scores 0.49–0.59), and the least vulnerable (scores 0.33–0.48).

The Vais and Wcv indexes are useful tools for evaluating the vulnerability of aquatic species and wetland communities, providing valuable information for defining conservation strategies.
Gamma‐delta (γδ) T cell‐derived cytokines (IL‐4, IL‐17, IFN‐γ and IL‐10) and their possible implications for atopic dermatitis development
Authors: Fagundes Beatriz Oliveira , de‐Sousa Thamires Rodrigues , Victor Jefferson Russo
Published: July 2022

Atopic dermatitis (AD) is a chronic disease related to skin disorders that affect individuals in their childhood and can persist or start in adulthood. Patients affected by this disease commonly show skin lesions on the body surface (mainly on the upper and lower limbs) and allergic rhinitis or asthma crises. Looking at the disease from a molecular perspective, the major cytokines involved in inflammatory skin diseases, not only AD, include IL‐4, IL‐17, IFN‐γ and IL‐10. Although they can produce these cytokines and infiltrate the affected epithelia in patients with AD, γδ T cells are still almost unexplored. In this update, we briefly discuss the involvement of IL‐4, IL‐17, IFN‐γ and IL‐10 in the pathophysiology of AD and the possible role of γδ T cells during the inflammatory process.
Evaluation of green solvent as an environment friendly alternative for milk fat extraction from ghee residue (clarified butter sediment waste)
Authors: Wani Aakash Dadarao , Prasad Writdhama , Khamrui Kaushik , Hussain Shaik Abdul , Deep Ankit
Published: July 2022

Ghee residue (clarified butter sediment waste) is a fat‐rich by‐product (containing 50–70% fat, weight basis) obtained during ghee (clarified butter fat) preparation. Conventionally used fat extraction methods from ghee residue (GR) are energy intensive and generates huge amount of waste water. In the present study, solvent extraction was explored for milk fat separation from GR at different extraction temperatures using green solvents, viz., ethyl acetate (EA) and di‐methyl carbonate (DMC). Changes in differential scanning calorimetry profile, fatty acid profile, dynamic rheology, FTIR spectroscopy and colour values of the solvent extracted fat were studied. Increasing the solvent extraction temperature increased the fat extraction efficacy from 45.62% to 49.22% for DMC and from 48.70% to 52.16% for EA. Considering the fat extraction efficacy, fat extraction from GR was found suitable using EA at 65°C extraction temperature. Fat extraction from GR using the selected green solvent, that is EA needed only 57% (18 000 J g−1 of GR) of energy as compared to conventional method (31 500 J g−1 of GR) with no wastewater generation.
Clinical assessment for pulmonary hypertension in interstitial lung disease
Authors: Chan Roseanne K. , Horrigan Mark , Goh Nicole S. L. , Khor Yet H.
Published: July 2022

Background

Pulmonary hypertension (PH) is an important complication of interstitial lung disease (ILD), as its development confers a poor prognosis. There are no specific recommendations for methods of assessment for PH in ILD populations.

Aims

To determine current assessment practices for PH in an Australian ILD centre.

Methods

In the Austin Health ILD database, 162 consecutive patients with idiopathic pulmonary fibrosis or connective tissue disease‐associated ILD were identified and retrospectively evaluated for methods of PH assessment with transthoracic echocardiography (TTE), serum N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and right heart catheterisation (RHC) in relation to patient demographic and physiological parameters.

Results

The median follow‐up was 30 (14.4–56.4) months. At baseline, vital capacity was 80.0 ± 18.4% predicted, and diffusing capacity for carbon monoxide was 59.6 ± 15.2% predicted. Evaluation for PH was performed in 147 (90.7%) patients, among whom 105 (64.8%) had TTE performed at least once. At the initial TTE, 33.7% patients had high probability of PH, defined as RVSP >40 mmHg + RAp and/or right ventricular dysfunction. At the time of the most recent TTE, these criteria were met in 45 (52.3%) patients. Elevated serum NT‐proBNP levels during the first year were observed in 47 (38.8%) patients. Only 14 (8.6%) patients had RHC.

Conclusion

Our institutional PH assessment practice in ILD demonstrates a substantial prevalence of probable PH at baseline. As new therapies emerge for the treatment of PH in ILD, well‐defined screening practices are important in this population for early identification and optimal management.
COVID vaccination can be performed in patients with a history of allergic reactions to the vaccines or their components: experience from a specialist clinic in South Australia
Authors: Tunbridge Matthew , Perkins Griffith , Lee Maverick , Salehi Tania , Ryoo Dongjae , Kette Frank , Smith William , Gold Michael , Le Thanh‐Thao Adriana , Yuson Chino , Hissaria Pravin
Published: July 2022

Background

The development of vaccines against SARS‐CoV2 has been a key public health response to the COVID‐19 pandemic. However, since their introduction, there have been reports of anaphylactic reactions to vaccines in individuals with history of allergic reactions to other vaccines, excipients or to COVID vaccines.

Aim

A dedicated adult COVID vaccine allergy clinic with a standardised allergy testing protocol was set up to investigate safety and suitability of available COVID vaccines in Australia.

Methods

Patients referred to a state‐wide COVID‐19 vaccine allergy clinic between March and August 2021 with a history of allergy underwent skin‐prick testing and intradermal testing to both available vaccine formulations (BNT162b2 and ChAdOx1‐S), excipients (polyethylene glycol and polysorbate 80), excipient‐containing medications and controls. Basophil activation testing was conducted in few subjects with convincing history of immediate type reactions.

Results

Fifty‐three patients underwent testing for possible excipient allergy (n = 19), previous non–COVID vaccine reaction (n = 13) or previous reaction to dose 1 of COVID‐19 vaccine (n = 21). Patients were predominantly female (n = 43, 81%), aged 18–83 (median 54) years. Forty‐four patients tested negative and 42 of these received at least their first dose of a COVID‐19 vaccine. Nine patients tested positive to excipients or excipient‐containing medication only (n = 3), or vaccines (n = 6). Five patients were positive to just BNT162b2, 3/5 have been vaccinated with ChAdOx1‐S. One who was skin test positive to both vaccines, but negative BAT to ChAdOx1‐S was successfully vaccinated with ChAdOx1‐S.

Conclusion

Even in a high‐risk population, most patients can be vaccinated with available COVID‐19 vaccines. This paper reports local experiences using a combined allergy testing protocol with skin testing and BAT during the pandemic.
Pulled in opposite directions: A joint consideration of supply and demand uncertainty in supply chain decision‐making
Authors: Bendoly Elliot , Boyer Ken , Craig Nate , Paul Somak
Published: July 2022

Supply chain inventory management decisions are complicated by the presence of both downstream (demand) and upstream (supply) uncertainties. Prior research shows that each type of uncertainty leads to specific decision biases. Demand uncertainty induces a pull‐to‐center bias, wherein orders are drawn away from the optimal ordering decision in the direction of expected demand. Supply uncertainty elicits a diversification bias, wherein inventory managers tend to source from multiple suppliers, even when sole sourcing is optimal. Our research employs a controlled laboratory experiment to study these biases when both types of uncertainty—that is, supply and demand uncertainty—are present. Our results show that the presence of both supply and demand uncertainty has a more nuanced effect on decision biases than does either type of uncertainty alone. Demand uncertainty can elicit and influence the diversification bias, even in the absence of supply uncertainty. Moreover, supply uncertainty affects the magnitude of the pull‐to‐center bias. Our work reveals the need for further attention from supply chain academics and managers on how supply and demand uncertainty jointly affect inventory managers’ decisions.
Attractiveness and nutritional effects of flowers on the survival of a dipteran pest and its parasitoids
Authors: Rossetti María Rosa , Salvo Adriana , Videla Martín
Published: July 2022

Flower addition is commonly used worldwide to benefit parasitoids and improve conservation biological control of pests. However, biological control enhancement via flower addition depends on both flower attractiveness and the responses of parasitoid and pest species to flower resources. Here, we experimentally compared the effects of two Apiaceae flowering species (Conium maculatum and Coriandrum sativum) with those of water, honey and no resource treatments on longevity and survival of adults of the leafminer Liriomyza huidobrensis and two hymenopteran parasitoids (Chrysocharis flacilla and Phaedrotoma scabriventris). We also examined the attractiveness of flowers of both plant species to the leafminer and P. scabriventris adults. The provision of flowers increased longevity and survival of the three insect species with respect to water and no resource treatments. The effects of honey on longevity were similar to or even higher than those of flowers, depending on the insect species, whereas water only increased the longevity of P. scabriventris in relation to no resource treatments. In attractiveness trials, P. scabriventris preferred C. maculatum flowers, whereas L. huidobrensis showed no preference for flower species. Our findings indicate that both plant species have potential as floral resources in biological control, since two parasitoid species benefited from flowers. However, these plant species must be cautiously considered because L. huidobrensis also improved its fitness when provided with both floral resources. The present work highlights the need to simultaneously study parasitoid and herbivore food needs and flower attractiveness, especially in dipteran pests, in order to achieve a successful biological control.
Gut microbiota from nCAL patients promotes colon anastomotic healing by inducing collagen synthesis in epithelial cells
Authors: Jin Xiangren , Liu Yang , Yan Wei , Shi Shang , Liu Lujia , Lin Baiqiang , Guo Xiao , Cai Ting , Wei Yunwei
Published: July 2022

Background and Aims

Colon anastomotic leak (CAL) is considered one of the most feared and serious postoperative complications in colorectal cancer (CRC) patients, with no effective prevention strategies to date. Based on previous studies, gut microbiota is associated with anastomotic healing, but its ability to effectively promote anastomotic healing remains largely unknown.

Methods

We performed a clinical study to analyze the gut microbiota profiling in CRC patients who developed CAL and those who did not (nCAL) using 16S‐rRNA‐based next‐generation sequencing (NGS). To investigate these changes in an in vivo model, we performed fecal microbiota transplantation in a colon anastomosis rat experimental model to elucidate the causal effect between gut microbiota and anastomotic healing. Notably, RNA‐seq in the anastomotic tissue of the latter experimental model was utilized to discover the potential molecular mechanism.

Results

Our analysis implicated that gut microbiota profiling was profoundly different between CAL and nCAL patients. Strikingly, the rat experimental model transplanted with fecal microbiota derived from nCAL patients demonstrated enhanced anastomotic healing properties. Moreover, collagen synthesis, EMT, and TGF‐β/Smad signaling pathways were upregulated in the same rats. Concordantly, we discovered that the better anastomotic healing profiling displayed in gut microbiota derived from nCAL patients is dependent on the TGF‐β/Smad‐induced EMT in vitro and in vivo.

Conclusions

Collectively, our clinical study identified the postoperative gut microbiota profile is associated with CAL in CRC patients. On the contrary, fecal microbiota from nCAL patients promotes anastomotic healing via TGF‐β/Smad‐induced EMT, with subsequent collagen synthesis and enhanced anastomosis healing.
(Landlord) Theory from the South: Empire and estates on a Punjabi Frontier
Authors: Raza Shozab
Published: July 2022

Theory has occasionally shaped agrarian transformations. Utilitarian theory, for instance, influenced British colonial land revenue policies, while modernization theory spurred, via the Green Revolution, the development of capitalist farming across the global South. Yet scholarship, when it has probed the mediation of theory in agrarian change, has largely centred on the intellectual activities of Western figures. In this paper, I examine an under‐appreciated theorizing actor: landlords in the global South. I explore landlords' concept‐work in the former “Punjab Frontier,” a region where Baloch chiefs collaborated with the British Raj to acquire localized magisterial powers, a paramilitary apparatus, and immense “landed estates” (jagirs). To overcome various crises, certain chiefs engaged with various imperial concepts—namely, property, race, progress, contract, and freedom—and re‐arranged their estates. By showing how these elites creatively embraced these concepts to maintain a colonial‐fortified hegemony, I also challenge those who overstate the emancipatory and decolonial possibilities of theory from the South.
Brain function complexity during dual‐tasking is associated with cognitive impairment and age
Authors: Peña Miguel , Petrillo Kelsi , Bosset Mark , Fain Mindy , Chou Ying‐hui , Rapcsak Steve , Toosizadeh Nima
Published: July 2022

Background and Purpose

Early diagnosis of cognitive impairment is important because symptoms can be delayed through therapies. Synaptic disconnections are the key characteristics of dementia, and through nonlinear complexity analysis of brain function, it is possible to identify long‐range synaptic disconnections in the brain.

Methods

We investigated the capability of a novel upper‐extremity function (UEF) dual‐task paradigm in the functional MRI (fMRI) setting, where the participant flexes and extends their arm while counting, to differentiate between cognitively normal (CN) and those with mild cognitive impairment (MCI). We used multiscale entropy (MSE) complexity analysis of the blood oxygen‐level dependent time‐series across neural networks and brain regions. Outside of the fMRI, we used the UEF dual‐task test, while the elbow kinematics were measured using motion sensors, to record the motor function score.

Results

Results showed 34% lower MSE values in MCI compared to CN (p<.04 for all regions and networks except cerebellum when counting down by one; effect size = 1.35±0.15) and a negative correlation between MSE values and age (average r2 of 0.30 for counting down by one and 0.36 for counting backward by three). Results also showed an improvement in the logistic regression model sensitivity by 14‐24% in predicting the presence of MCI when brain function measure was added to the motor function score (kinematics data).

Conclusions

Current findings suggest that combining measures of neural network and motor function, in addition to neuropsychological testing, may provide an accurate tool for assessing early‐stage cognitive impairment and age‐related decline in cognition.
Adolescents' Retributive and Restorative Orientations in Response to Intergroup Harms in Schools
Authors: Pareja Conto Laura , Restrepo Angelica , Recchia Holly , Velez Gabriel , Wainryb Cecilia
Published: July 2022

This mixed‐methods study examined how adolescents understand and evaluate different ways to address intergroup harms in schools. In individual interviews, 77 adolescents (Mage = 16.49 years; 39 girls, 38 boys) in Bogotá, Colombia, responded to hypothetical vignettes wherein a rival group at school engaged in a transgression against their group. Adolescents reported that students who were harmed should and would talk to school authorities, but also noted they would likely retaliate. In terms of teacher‐sanctioned responses to harm, youth endorsed compensation most strongly, followed by apologies, and rated suspension least positively. Youths' explanations for their endorsement of different disciplinary practices reflected varied concerns, including their perceptions of how justice is best achieved and how restoration could be attained.
Spinning straw into gold: Innovation recycling, innovation sourcing modes, and innovation ability in Sub‐Saharan Africa
Authors: Li Rebecca Yu , Sousa Carlos M. P. , He Xinming , Hu Yansong
Published: July 2022

As innovation is inherently risky and uncertain, it is common for firms to suspend or abandon new product/service development projects that cannot achieve pre‐defined objectives. Multiple cases exist where firms have attempted to resume the development of an innovative product or service after previously suspending or abandoning it prior to completion. Research on this important innovation recycling activity is surprisingly scarce, despite its critical role in mitigating risk in the context of high environmental uncertainty. We draw our inferences from Sub‐Saharan Africa (SSA), where innovation resources are relatively limited and environmental uncertainty and institutional voids prevail, a context that encourages the use of innovation recycling. This study examines how innovation recycling influences a firm's innovation ability and the moderating impact of innovation sourcing modes using a knowledge‐based view of the firm and arguments from transaction cost economics. We retrieved data from the World Bank Enterprise Survey and the Innovation Follow‐up Survey of 1076 firms located in eight SSA countries (Ghana, Malawi, Namibia, South Sudan, Sudan, Tanzania, Uganda, and Zambia) spanning from 2011 to 2014 to test our conceptual model. Our findings show that (1) innovation recycling has a positive influence on a firm's innovation ability and (2) this relationship is moderated by different innovation sourcing modes. These findings enrich the theory and imply that firms operating in developing countries need to develop innovation recycling by focusing on sourcing knowledge within, rather than across, firm boundaries.
Stress reactivity in salivary cortisol and electrocardiogram in adolescents: Investigating sleep disturbances and insomnia
Authors: Kater Maren‐Jo , Werner Anika , Schlarb Angelika A. , Lohaus Arnold
Published: July 2022

This study examined the role of sleep disturbances and insomnia in the context of stress reactivity in adolescence. One‐hundred and thirty‐five 11–18 year olds (Mage = 14.2 years, SD = 1.9, 52% female) completed the Trier Social Stress Test for Children. Salivary cortisol and subjective stress ratings were collected at six time points, and heart rate as well as heart rate variability were measured pre‐, during and post‐stress induction. Additionally, sleep disturbances and insomnia diagnosis were assessed by a self‐report questionnaire and a sleep interview. Robust mixed models investigated if adolescents with compared with adolescents without (a) sleep disturbances and (b) insomnia differ regarding cortisol, heart rate, heart rate variability and psychological stress reactivity considering gender effects. The results indicated that boys with high sleep disturbances showed higher cortisol activity compared with boys with low sleep disturbances, B = 0.88, p < 0.05. Moreover, in boys with insomnia, heart rate and alpha 1 significantly differ less than in boys without insomnia. These findings support the notion of sex differences regarding the association between poor sleep and increased activity of the hypothalamic–pituitary–adrenal axis, and a less adaptable autonomic nervous system in boys in response to an experimental social stress task.
The landscape of common genetic drivers and DNA methylation in low‐grade (epilepsy‐associated) neuroepithelial tumors: A review
Authors: Jesus‐Ribeiro Joana , Rebelo Olinda , Ribeiro Ilda Patrícia , Pires Luís Miguel , Melo João Daniel , Sales Francisco , Santana Isabel , Freire António , Melo Joana Barbosa
Published: July 2022

Low‐grade neuroepithelial tumors (LNETs) represent an important group of central nervous system neoplasms, some of which may be associated to epilepsy. The concept of long‐term epilepsy‐associated tumors (LEATs) includes a heterogenous group of low‐grade, cortically based tumors, associated to drug‐resistant epilepsy, often requiring surgical treatment. LEATs entities can sometimes be poorly discriminated by histological features, precluding a confident classification in the absence of additional diagnostic tools. This study aimed to provide an updated review on the genomic findings and DNA methylation profiling advances in LNETs, including histological entities of LEATs. A comprehensive search strategy was conducted on PubMed, Embase, and Web of Science Core Collection. High‐quality peer‐reviewed original manuscripts and review articles with full‐text in English, published between 2003 and 2022, were included. Results were screened based on titles and abstracts to determine suitability for inclusion, and when addressed the topic of the review was screened by full‐text reading. Data extraction was performed through a qualitative content analysis approach. Most LNETs appear to be driven mainly by a single genomic abnormality and respective affected signaling pathway, including BRAF p.V600E mutations in ganglioglioma, FGFR1 abnormalities in dysembryoplastic neuroepithelial tumor, MYB alterations in angiocentric glioma, BRAF fusions in pilocytic astrocytoma, PRKCA fusions in papillary glioneuronal tumor, between others. However, these molecular alterations are not exclusive, with some overlap amongst different tumor histologies. Also, clustering analysis of DNA methylation profiles allowed the identification of biologically similar molecular groups that sometimes transcend conventional histopathological classification. The exciting developments on the molecular basis of these tumors reinforce the importance of an integrative histopathological and (epi)genetic classification, which can be translated into precision medicine approaches.