bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy and precision of sonographic fetal weight estimation in Sweden
Authors: Lindström Linda , Cnattingius Sven , Axelsson Ove , Granfors Michaela
Published: March 2023

Introduction

Fetal growth assessment by ultrasound is an essential part of modern obstetric care. The formula by Persson and Weldner for estimated fetal weight (EFW), used in Sweden since decades, has not yet been evaluated. The objective of this study was to evaluate accuracy and precision of the formula by Persson and Weldner, and to compare it to two other formulae using biparietal diameter instead of head circumference.

Material and methods

The study population consisted of 31 521 singleton pregnancies delivered at 22+0 gestational weeks or later, with an ultrasound EFW performed within 2 days before delivery, registered in the Swedish Pregnancy Register between 2014 and 2021. Fetal biometric ultrasound measurements were used to calculate EFW according to the formulae by Persson and Weldner, Hadlock 2 and Shepard. Bland–Altman analysis, systematic error (mean percentage error), random error (standard deviation [SD] of mean percentage error), proportion of weight estimates within ±10% of birthweight, and proportion with underestimated and overestimated weight was calculated. Moreover, calculations were made after stratification into small, appropriate, and large for gestational age (SGA, AGA and LGA), respectively, and gestational age at examination.

Results

For the formula by Persson and Weldner, MPE was −2.7 (SD 8.9) and the proportion of EFW within ±10% from actual birthweight was 76.0%. MPE was largest for fetuses estimated as severe SGA (<3rd percentile, −5.4) and for the most preterm fetuses (<24 weeks, −5.4). For Hadlock 2 and Shepard's formulae, MPE were 3.9 (SD 8.9) and 3.4 (SD 9.7), respectively, and the proportions of EFW within ±10% from actual birthweight were 69.4% and 67.1%, respectively. MPE was largest for fetuses estimated as severe LGA (>97th percentile), 7.6 and 9.4, respectively.

Conclusions

The recommended Swedish formula by Persson and Weldner is generally accurate for fetal weight estimation. The systematic underestimation of EFW and random error is largest in extreme preterm and estimated SGA‐fetuses, which is of importance in clinical decision making. The accuracy of EFW with the formula by Persson and Weldner is as good as or better than Hadlock 2 and Shepard's formulae.
Key outcomes in childbirth: Development of a perinatal core outcome set for management of labor and delivery at or near term
Authors: Savchenko Julia , Asp Malin , Blomberg Marie , Elvander Charlotte , Hagman Anna , Pegelow Halvorsen Cecilia , Lindqvist Pelle , Nelander Maria , Skiöld Béatrice , Brismar Wendel Sophia
Published: March 2023

Introduction

Consistency and relevance of perinatal outcome measures are necessary basics for obstetric research, audit, and clinical counseling. Still, there is an unwarranted variation in reported perinatal outcomes, which impairs research synthesis, validity, and implementation, as well as clinical benchmarking and longitudinal comparisons. The aim of this study was to develop a short‐term perinatal (fetal and neonatal) Core Outcome Set to be used in research and quality assurance of management of labor and delivery at or near term.

Material and methods

The methods were guided by the Core Outcome Measures in Effectiveness Trials Initiative Handbook. The project was prospectively registered on July 2, 2020 in the Core Outcome Measures in Effectiveness Trials (COMET) data base (reference number 1593). A list of potential outcomes was created based on a systematic review of studies evaluating interventions for peripartum management at or near term (≥34 weeks of gestation), including decisions regarding timing and type of onset of labor, intrapartum care, and mode of delivery. The list was entered into a two‐round Delphi survey with predefined consensus criteria. Participants (n = 67) included clinicians, researchers, lay persons with experience of childbirth (patient representatives), and other stakeholders. A consensus meeting was held to reach a final agreement.

Results

Response rates were 82.1% (55/67) and 92.7% (51/55) for the first and second Delphi rounds, respectively. In total, 17 outcomes were included in the final core outcome set, reflecting mortality, health or morbidity, including asphyxia, central nervous system status, infection, neonatal resuscitation and admission, breastfeeding and mother‐infant interaction, operative delivery due to fetal distress, as well as birthweight and gestational age. Two of these outcomes were suggested by patient representatives.

Conclusions

The Swedish Perinatal Core Outcome Set (SPeCOS) study involved a broad circle of relevant stakeholders and reached consensus on a minimal set of perinatal outcomes that should be collected and reported in a standardized way in all future studies on management of labor and delivery at or near term, regardless of the specific population or condition studied. This could improve obstetric research, evidence synthesis, uptake, implementation, and adherence, as well as clinical practice, audit, and comparisons in childbirth care.
Evaluation of diagnostic and prognostic candidate biomarkers in drug‐induced liver injury vs. other forms of acute liver damage
Authors: Cueto‐Sánchez Alejandro , Niu Hao , Álvarez‐Álvarez Ismael , López‐Longarela Bárbara , Del Campo‐Herrera Enrique , Ortega‐Alonso Aida , García‐Cortés Miren , Pinazo‐Bandera José , Sanabria‐Cabrera Judith , Díaz‐Mochón Juan José , Lucena M. Isabel , Andrade Raúl J. , Stephens Camilla , Robles‐Díaz Mercedes
Published: March 2023

Aims

Detection and characterization of idiosyncratic drug‐induced liver injury (DILI) currently rely on standard liver tests, which are suboptimal in terms of specificity, sensitivity and prognosis. Therefore, DILI diagnosis can be delayed, with important consequences for the patient. In this study, we aimed to evaluate the potential of osteopontin, cytokeratin‐18 (caspase‐cleaved: ccK18 and total: K18), α‐glutathione‐S‐transferase and microRNA‐122 as new DILI biomarkers.

Methods

Serial blood samples were collected from 32 DILI and 34 non‐DILI acute liver injury (ALI) cases and a single sample from 43 population controls without liver injury (HLC) and analysed using enzyme‐linked immunosorbent assay (ELISA) or single‐molecule arrays.

Results

All biomarkers differentiated DILI and ALI from HLC with an area under receiver operator characteristic curve (AUC) value of >0.75 but were less efficient in distinguishing DILI from ALI, with ccK18 (0.79) and K18 (0.76) demonstrating highest potential. However, the AUC improved considerably (0.98) for ccK18 when comparing DILI and a subgroup of autoimmune hepatitis cases. Cytokeratin‐18, microRNA‐122 and α‐glutathione‐S‐transferase correlated well with traditional transaminases, while osteopontin correlated most strongly with the international normalized ratio (INR).

Conclusions

ccK18 appears promising in distinguishing DILI from autoimmune hepatitis but less so from other forms of acute liver injury. Osteopontin demonstrates prognostic potential with higher levels detected in more severe cases regardless of aetiology.
Prototypicality at the intersection of gender and sexual orientation
Authors: Klysing Amanda
Published: March 2023

The intersectional invisibility hypothesis (IIH) states that members of multiply marginalized groups experience intersectional invisibility by not being seen as prototypical for either of their constitutive groups due to the influence of heterocentrism and androcentrism. That is, a lesbian woman may not be represented in relation to either the category ‘woman’ or the category ‘homosexual people’. Two online experiments conducted in Sweden and the United Kingdom (N = 1923) tested predictions from the IIH at different intersections of specific genders (woman and man) and sexual orientations (heterosexuality, homosexuality and bisexuality) using an attribute generation task and direct similarity ratings. Results show strong support for the influence of heterocentrism: Only prototypes for heterosexual women/men match general prototypes for women/men. Androcentrism influenced the prototype for ‘homosexual people’, which had a stronger match with the prototype for gay men compared with lesbian women. In contrast, bisexual women were seen as more prototypical ‘bisexual people’ than bisexual men were. Psychological research conducted on general gender groups may therefore only be applicable to heterosexual individuals, while research on homosexual people in general may be applicable mainly to gay men.
The roles of RGS proteins in cardiometabolic disease
Authors: McNeill Samantha M. , Zhao Peishen
Published: March 2023

G protein‐coupled receptors (GPCRs) are the most prominent receptors on the surface of the cell and play a central role in the regulation of cardiac and metabolic functions. GPCRs transmit extracellular stimuli to the interior of the cells by activating one or more heterotrimeric G proteins. The duration and intensity of G protein‐mediated signalling are tightly controlled by a large array of intracellular mediators, including the regulator of G protein signalling (RGS) proteins. RGS proteins selectively promote the GTPase activity of a subset of Gα subunits, thus serving as negative regulators in a pathway‐dependent manner. In the current review, we summarise the involvement of RGS proteins in cardiometabolic function with a focus on their tissue distribution, mechanisms of action and dysregulation under various disease conditions. We also discuss the potential therapeutic applications for targeting RGS proteins in treating cardiometabolic conditions and current progress in developing RGS modulators.

LINKED ARTICLES

This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc
Novel therapeutic approaches to target neurodegeneration
Authors: de la Fuente Alerie G. , Pelucchi Silvia , Mertens Jerome , Di Luca Monica , Mauceri Daniela , Marcello Elena
Published: March 2023

Ageing is the main risk factor common to most primary neurodegenerative disorders. Indeed, age‐related brain alterations have been long considered to predispose to neurodegeneration. Although protein misfolding and the accumulation of toxic protein aggregates have been considered as causative events in neurodegeneration, several other biological pathways affected by brain ageing also contribute to pathogenesis. Here, we discuss the evidence showing the involvement of the mechanisms controlling neuronal structure, gene expression, autophagy, cell metabolism and neuroinflammation in the onset and progression of neurodegenerative disorders. Furthermore, we review the therapeutic strategies currently under development or as future approaches designed to normalize these pathways, which may then increase brain resilience to cope with toxic protein species. In addition to therapies targeting the insoluble protein aggregates specifically associated with each neurodegenerative disorder, these novel pharmacological approaches may be part of combined therapies designed to rescue brain function.
The application of targeted protein degradation technologies to G protein‐coupled receptors
Authors: Keen Alastair C. , Jörg Manuela , Halls Michelle L.
Published: March 2023

The ubiquitin‐proteasome system is one of the major pathways for the degradation of cellular proteins. In recent years, methods have been developed to exploit the ubiquitin‐proteasome system to artificially degrade target proteins. Targeted protein degraders are extremely useful as biological tools for discovery research. They have also been developed as novel therapeutics with several targeted protein degraders currently in clinical trials. However, almost all targeted protein degrader technologies have been developed for cytosolic proteins. The G protein‐coupled receptor (GPCR) superfamily is one of the most important classes of drug targets, yet only limited examples of GPCR degradation exist. Here, we review these examples and provide a perspective on the different strategies that have been used to apply targeted protein degradation to GPCRs. We also discuss whether alternative approaches that have been used to degrade other integral membrane proteins could be applied to the degradation of GPCRs.

LINKED ARTICLES

This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc
Source‐to‐sink mass‐balance analysis of an ancient wave‐influenced sediment routing system: Middle Jurassic Brent Delta, Northern North Sea, offshore UK and Norway
Authors: Okwara Ikenna C. , Hampson Gary J. , Whittaker Alexander C. , Roberts Gareth G. , Ball Patrick W.
Published: March 2023

Sediment mass‐balance analysis provides key constraints on stratigraphic architecture and its controls. We use the data‐rich Middle Jurassic Brent Delta sediment routing system in the proto‐Viking Graben, Northern North Sea, to estimate sediment budgets and mass‐balance between source areas and depositional sinks. Published studies are synthesised to provide an age‐constrained sequence stratigraphic framework, consisting of four previously defined genetic sequences (J22, J24, J26, J32). Genetic sequence J32 (3.9 Myr) records transverse progradation of basin‐margin deltas, sourced from the Shetland Platform to the west and Norwegian Landmass to the east. Genetic sequences J24 (1.1 Myr) and J26 (0.9 Myr) record the rapid progradation and subsequent aggradation of the Brent Delta along the basin axis, sourced from the uplifted Mid‐North Sea High to the south, and the western and eastern source regions. Genetic sequence J32 (2.2 Myr) records the retreat of the Brent Delta. Sediment budgets for the four genetic sequences are estimated using palaeogeographical reconstructions, isopach maps, and sedimentological analysis of core and well‐log data. The estimated net‐depositional sediment budget for the mapped Brent Delta system is 2.0–2.8 Mt/year. Temporal variations in net‐depositional sediment budget were driven by changes in tectonic boundary conditions, such as the onset of uplift before the deposition of genetic sequence J24. Over the same time period, the Shetland Platform, Norwegian Landmass and Mid‐North Sea High source regions are estimated to have supplied 2.3–5.6, 5.0–14.1, and 2.8–9.4 Mt/year of sediment, respectively, using the BQART sediment load model and independent geometrical reconstruction of eroded volumes, which are constrained by isostatic uplift estimates based on the geochemistry of syn‐depositional volcanic rocks. The net‐depositional sediment budget in the sink is an order‐of‐magnitude smaller than the total sediment budget supplied by the source regions (13.9–23 Mt/year). This discrepancy suggests that along‐shore transport by wave‐generated currents into the coeval Faroe‐Shetland Basin and/or down‐dip transport by gravity flows into the coeval western Møre Basin played a key role in redistributing sediments away from the Brent Delta system.
Emotional symptoms and cognitive function outcomes of subthalamic stimulation in Parkinson's disease depend on location of active contacts and the volume of tissue activated
Authors: Liang Kun , Li Ren‐Peng , Gao Yuan , Liu Chong , Wang Qiao , Gao Dong‐Mei , Wang Hui‐Min , Zou Liang‐Ying , Zhang Xin , Han Chun‐Lei , Zhang Jian‐Guo , Meng Fan‐Gang
Published: March 2023

Background

Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), that can improve patients' motor and non‐motor symptoms. However, there are differences in the improvement of patients' emotional symptoms and cognitive function.

Objective

To investigate the impact of active contact location and the volume of tissue activated (VTA) on patients' emotional symptoms and cognitive function in STN‐DBS in PD.

Methods

A total of 185 PD patients were included in this study. We evaluated them using the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale, Hamilton Anxiety Scale (HAM‐A), Hamilton Depression Scale (HAM‐D), Montreal Cognitive Assessment (MoCA), and Mini‐Mental State Examination (MMSE) scales at the preoperative, 1‐ and 12‐month postoperative time points. Leads were positioned in standard space using the Lead‐DBS toolbox, and VTA was calculated for analysis.

Results

When the lead active contact was closer to the ventral side of the STN, the patients' HAM‐A improvement rate was higher, and when the active contact was closer to the anterior and dorsal sides of the STN, the patients' MoCA improvement rate was higher. Stimulation of the sensorimotor zone was more favorable to the improvement of HAM‐A and HAM‐D in patients. And, the stimulation of the associative zone was more favorable to the improvement of MoCA in patients.

Conclusion

Our results provide evidence that the 12‐month outcomes of cognitive function and emotional symptoms in PD patients with STN‐DBS were closely related to the specific location of the active contacts in the STN and influenced by the VTA.
Surgical treatment of stomal prolapse: A systematic review and meta‐analysis of the literature
Authors: Garoufalia Zoe , Mavrantonis Sofoklis , Emile Sameh Hany , Gefen Rachel , Horesh Nir , Freund Michael R. , Wexner Steven D.
Published: March 2023

Aim

This study aimed to assess success, recurrence, and overall complication rates among different surgical procedures for stomal prolapse.

Methods

This study was a PRISMA‐compliant systematic review. PubMed, Scopus, and Google Scholar were searched until March 2022. Studies that assessed surgical treatments of stomal prolapse in adults were included. The primary outcome was recurrence of stomal prolapse and the secondary outcome was 30‐day complications. A random‐effect meta‐analysis was used to estimate the weighted mean rates of recurrence.

Results

Six studies published (111 patients; 103 males) were included. 52 (46.8%) patients had end colostomies, 35 (31.5%) had loop colostomies. Seven procedures were assessed and included local stoma reconstruction (40%), stapled local repair (27%), modified Altemeier technique (10%), mesh strip repair (9%), stoma relocation (6%) redo laparotomy repair (5%), and colectomy and end ileostomy (3%). The weighted mean recurrence rate after local stoma reconstruction was 37.2% (95% CI: −1.8 to 76.3), higher than that after the stapled local repair technique (14.9%; 95% CI: 1.7–28.2). The crude recurrence rate of the modified Altemeier technique was 20%, and of stoma relocation was 66.6%. No recurrence was detected after the mesh strip technique (n = 10). The median follow‐up ranged between 7 months and 2.5 years.

Conclusion

Several surgical techniques are available to treat stomal prolapse. Local stoma reconstruction may be associated with high rates of recurrence while the stapled local repair and modified Altemeier procedure has relatively low recurrence. Further larger studies are needed to compare the efficacy of these techniques.
The roles of polymer relaxation phenomena, aqueous dye solubility and the physical properties of water in the mechanism of adsorption of a disperse dye on poly(ethylene terephthalate) fibres: part 5 analysis of polymer relaxation phenomena for different polymers
Authors: Burkinshaw S. M. , Liu K.
Published: March 2023

The temperature dependent uptake of a commercial disperse dye on cotton and polyamide 66 fabrics at dyeing temperatures between 30°C and 130°C adhered to the Williams–Landel–Ferry equation, insofar as, very good correspondence was observed between plots of experimentally determined colour strength data points (log1/fk) and the respective structural relaxation times of the cellulose and nylon 66 polymers (logaT data points), as a function of the parameter (T − Tg). Adsorption of the dye on both types of fibre therefore concurs with the fundamental precept of the free volume model of dye diffusion. Comparison of the adherence of the uptake of the commercial dye on cotton and polyamide 66 fabrics with that secured on polyester fabric revealed that despite the major chemical and physical differences between the three types of fibre, the same dyeing mechanism likely applies to each fibre type. The marked temperature dependent uptake of the commercial grade disperse dye each of the three types of substrate is the consequence of two, different, but inherently interconnected, thermally activated phenomena, namely the relaxation times of the molecular rearrangements occurring within the respective cellulose, nylon 66 or poly(ethylene terephthalate) macromolecule, in which polymer glass transition assumes the principal role, and the aqueous solubility of the commercial grade disperse dye.
Assessing translocation success and long‐distance homing in riverine turtles 10 years after a freshwater oil spill
Authors: Otten Joshua G. , Williams Lisa , Refsnider Jeanine M.
Published: March 2023

Wildlife translocation is often used as a mitigation strategy for construction projects and other disturbances to habitat. In 2010, one of the largest freshwater oil spills in the United States occurred in the Kalamazoo River in Michigan, when over 3.2 million L of diluted bitumen crude oil impacted nearly 56 km of riverine habitat. During 2010 and 2011 cleanup efforts, 686 northern map turtles (Graptemys geographica) were captured from oil‐impacted stretches of the river, cleaned, rehabilitated, and translocated 2.5–84.3 km from their original capture location. The goal of this translocation effort was to release turtles within the same watershed, but away from ongoing cleanup operations, so individuals could potentially return to their original home range after it had been cleaned of oil and restored. In this study, we evaluated the success of translocation as an emergency mitigation strategy for freshwater turtles by quantifying recapture probability and homing by northern map turtles translocated varying distances from their home ranges. During subsequent years of survey up to 10 years post‐spill, 230 of the translocated turtles were recaptured, of which 104 exhibited homing by returning to their original home ranges. Turtles translocated to sites nearest their original capture location had a higher probability of recapture and homing than those translocated further away. Females had a higher probability of returning to original home ranges than males when translocated greater distances. In addition, four females and one male are known to have traveled >50 km between capture and release locations, which to our knowledge is the greatest travel distance recorded for any freshwater turtle species in the United States. Our results demonstrate that riverine turtles have considerable homing ability when displaced long distances, which has important implications for design and success of translocation projects.
Multi‐site interaction turnover in flea–mammal networks from four continents: Application of zeta diversity concept and multi‐site generalised dissimilarity modelling
Authors: Krasnov Boris R. , Khokhlova Irina S. , Kiefer Mathias S. , Kiefer Daniel , Lareschi Marcela , Matthee Sonja , Sanchez Juliana P. , Shenbrot Georgy I. , Stanko Michal , van der Mescht Luther
Published: March 2023

We studied patterns of changes in host–flea interactions measured as total turnover (TT) which can be partitioned into components, namely species turnover (ST), interaction rewiring (RW), and mixed turnover (MX) in networks from Europe, Asia, Africa, and South America, applying a multi‐site interaction turnover metric. We also searched for environmental drivers of TT and its components.

We asked whether (a) different components contribute differently to TT in rare versus common interactions (in terms of frequency of interaction occurrence); (b) relative roles of turnover components for rare and common interactions differ between continents; and (c) the environmental drivers of interaction turnover differ between turnover components, rare and common interactions, and/or continental networks.

Between‐network dissimilarity of interactions increased with an increase in the number of compared networks. Pure ST contributed the most to the turnover of rare interactions, whereas the turnover of common interactions was predominated by MX.

The effects of environmental factors, interaction richness, and spatial distance on TT and its components differed between continental networks, turnover components, and rare versus common interactions. Climate and vegetation exerted the strongest effects on (a) ST for rare (except Asia) and, to a lesser degree, common (South America) interactions, (b) RW for both rare and common interactions in Europe/Asia, and (c) MX for both rare and common interactions (except Africa). Interaction richness and spatial distance mainly influenced ST.

We conclude that the patterns of interaction turnover and its components were geographically invariant and did not depend on the identity of the interactors, whereas the drivers of the turnover differed between continental networks because of species‐specific responses to the environment.
Trajectories of the SARS‐CoV‐2 RNA load in patients with hematological malignancy
Authors: Mitsuyuki Satoshi , Nishikubo Masashi , Shimomura Yoshimitsu , Ohyama Yukie , Maruoka Hayato , Nasu Seiko , Kubo Tomoyo , Suzuki Yuta , Okada Naoki , Nakagawa Daishi , Kamijo Kimimori , Yamamoto Ryusuke , Nagai Yuya , Hiramoto Nobuhiro , Yoshioka Satoshi , Yonetani Noboru , Hasegawa Kohei , Kuroda Hirokazu , Hasuike Toshikazu , Doi Asako , Kondo Tadakazu , Ishikawa Takayuki
Published: March 2023

Objectives

The higher risk of prolonged viral shedding in coronavirus disease (COVID‐19) patients with hematological malignancies (HM) necessitates test‐based de‐isolation strategies. However, evidence to establish their appropriate isolation period is insufficient. This study investigated the factors affecting prolonged viral shedding and the requisite isolation period in these patients.

Methods

We retrospectively reviewed 14 COVID‐19 patients with HM between January and April 2022, who were subjected to our test‐based de‐isolation strategy, followed by analysis of the viral load trajectory. The viral loads of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) were evaluated using the cycle threshold (Ct) of the reverse‐transcription quantitative polymerase chain reaction. The trajectories were classified according to the time‐interval from COVID‐19 onset to the attainment of Ct values >30.

Results

The median interval between onset and attainment of a Ct value >30 was 22 days. Five patients with mild or moderate COVID‐19 without intense treatment histories achieved Ct values >30 within 20 days. The other nine patients needed more than 20 days, including three patients who did not meet this criterion during the observation period.

Conclusions

The SARS‐CoV‐2 viral load trajectories in patients with HM can be stratified by treatment history for the underlying HM and severity of COVID‐19.
Response rates of extra‐nodal diffuse large B cell lymphoma to anti‐CD19‐CAR T cells: A real word retrospective multicenter study
Authors: Beyar Katz Ofrat , Perry Chava , Grisariu‐Greenzaid Sigal , Yehudai‐Ofir Dana , Luttwak Efrat , Avni Batia , Zuckerman Tsila , Sdayoor Inbal , Stepensky Polina , Ringelstein‐Harlev Shimrit , Bar‐On Yael , Libster Diana , Sharvit Liat , Amit Odelia , Greenbaum Uri , Gold Ronit , Herishanu Yair , Benyamini Noam , Avivi Irit , Ram Ron
Published: March 2023

Chimeric antigen receptor T‐cells (CAR‐T) are widely used for the treatment of relapsed/refractory diffuse large B cell lymphoma (DLBCL). The data for CAR‐T cell therapy in patients with extra‐nodal (EN) lymphoma is restricted. We included 126 consecutive patients with DLBCL treated with commercially available CAR‐T cells (tisagenlecleucel, n = 100, 79.4% and axicabtagene ciloleucel, n = 26, 20.6%). At lymphodepletion, 72 of 126 (57%) patients had EN disease, 42 of 126 (33%) patients had nodal disease (ND)‐only and 12 of 126 (10%) showed no disease assessed by PET‐CT. There were no significant differences in CAR‐T related toxicities and in the median Progression free survival (PFS) between EN patients and ND (10.76 [95% CI: 7.8–13.6] vs. 14.1 [95% CI: 10–18.1] months, p = .126). Similarly, median overall survival (OS) was not significantly different (15.36 [95% CI 12.5–18.2] vs. 18.4 [95% CI 14.8–22.1] months, p = .100). Subgroup analysis according to the number of EN involved sites showed that median PFS and OS were significantly higher in patients with <3 EN sites (12.3 months [95% CI 9–15.5] vs. 4.28 months [95% CI 0.6–7.9], p = .010) compared to patients with >2 EN sites, respectively (16.5 months [95% CI 13.4–19.6] vs. 8.7 months [95% CI 4.6–12.8], p = .05). In multivariate cox regression analysis, increased number sites of EN disease and high lactate dehydrogenase (LDH) at lymphodepletion negatively impacted PFS (p = .021 and <.001, respectively), while sex, type of product administered, age and performance status did not predict PFS and OS. Of note, all the patients with involvement of gastrointestinal tract (n = 9), urinary tract (n = 9), or pharynx (n = 3) at lymphodepletion, progressed or had an early relapse. In conclusions, patients with >2 EN sites at lymphodepletion have significantly worse clinical outcomes compared to patients with <3 EN sites. Patients with specific sites of EN disease may demonstrate grim prognosis.
Fatigue and health‐related quality of life in paroxysmal nocturnal haemoglobinuria: A post hoc analysis of the pegcetacoplan PEGASUS trial data
Authors: Panse Jens , Wilson Koo , Fishman Jesse , Wojciechowski Piotr , Wdowiak Marlena , Horneff Regina , Patriquin Christopher J. , Oliver Monika , Hakimi Zalmai
Published: March 2023

Objectives

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, non‐malignant haematological disorder associated with disabling fatigue and reduced health‐related quality of life. Post hoc analysis of PEGASUS phase 3 trial (NCT03500549) characterised improvements in patient‐reported fatigue measured by functional assessment of chronic illness therapy‐fatigue (FACIT‐fatigue) instrument item‐level ratings for pegcetacoplan and eculizumab for the treatment of PNH.

Methods

Item‐level responder analysis was conducted on a ≥2‐level change from baseline (CFB) clinically important response (CIR) for the FACIT‐fatigue 13 individual items rated on a 5‐level Likert scale. We evaluated ≥2‐level change against the minimal clinically important difference (MCID) of the FACIT‐fatigue total score (≥5 points) and clinical parameters, haemoglobin (Hb; ≥1 g/dL) and normalised absolute reticulocyte count (ARC; 30–100 pg/cells). Logistic regressions estimated baseline‐to‐Week‐16 FACIT‐fatigue item‐level transitional probabilities; Kaplan–Meier analysis estimated time to FACIT‐fatigue item CIR.

Results

Pegcetacoplan versus eculizumab was associated with significantly greater odds of Week 16 CIR across 8/13 items and on total score MCID (OR [CI] = 11.19 [3.73, 33.57]) and faster times to responses. The item‐level CIR threshold also showed clinical relevance on Hb level and ARC normalization.

Conclusions

Compared with eculizumab, pegcetacoplan was associated with clinically meaningful greater improvements on a majority of FACIT‐fatigue items.
Quantification approaches for magnetic resonance imaging following intravenous gadolinium injection: A window into brain‐wide glymphatic function
Authors: Richmond Sutton B. , Rane Swati , Hanson Moriah R. , Albayram Mehmet , Iliff Jeffrey J. , Kernagis Dawn , Rosenberg Jens T. , Seidler Rachael D.
Published: March 2023

The glymphatic system is a brain‐wide network of perivascular pathways along which cerebrospinal fluid and interstitial fluid rapidly exchange, facilitating solute and waste clearance from the brain parenchyma. The characterization of this exchange process in humans has relied primarily upon serial magnetic resonance imaging following intrathecal gadolinium‐based contrast agent injection. However, less invasive approaches are needed. Here, we administered a gadolinium‐based contrast agent intravenously in eight healthy participants and acquired magnetic resonance imaging scans prior to and 30, 90, 180, and 360 min post contrast injection. Using a region‐of‐interest approach, we observed that peripheral tissues and blood vessels exhibited high enhancement at 30 min after contrast administration, likely reflecting vascular and peripheral interstitial distribution of the gadolinium‐based contrast agent. Ventricular, grey matter and white matter enhancement peaked at 90 min, declining thereafter. Using k‐means clustering, we identify distinct distribution volumes reflecting the leptomeningeal perivascular network, superficial grey matter and deep grey/white matter that exhibit a sequential enhancement pattern consistent with parenchymal contrast enhancement via the subarachnoid cerebrospinal fluid compartment. We also outline the importance of correcting for (otherwise automatic) autoscaling of signal intensities, which could potentially lead to misinterpretation of gadolinium‐based contrast agent distribution kinetics. In summary, we visualize and quantify delayed tissue enhancement following intravenous administration of gadolinium‐based contrast agent in healthy human participants.
Disadvantage and neurocognitive comorbidities in childhood idiopathic epilepsies
Authors: Schraegle William A. , Slomowitz Rebecca F. , Gundlach Carson , Hsu David A. , Almane Dace N. , Stafstrom Carl E. , Seidenberg Michael , Jones Jana E. , Hermann Bruce P.
Published: March 2023

Objective

This study was undertaken to characterize the relationship between neighborhood disadvantage and cognitive function as well as clinical, sociodemographic, and family factors in children with new onset idiopathic epilepsy and healthy controls.

Methods

Research participants were 288 children aged 8–18 years with recent onset epilepsy (CWE; n = 182; mean age = 12.2 3.2 years), healthy first‐degree cousin controls (HC; n = 106; mean age = 12.53.0), and one biological or adopted parent per child (n = 279). All participants were administered a comprehensive neuropsychological battery (reasoning, language, memory, executive function, motor function, and academic achievement). Family residential addresses were entered into the Neighborhood Atlas to determine each family's Area Deprivation Index (ADI), a metric used to quantify income, education, employment, and housing quality. A combination of parametric and nonparametric (χ2) tests examined the effect of ADI by group (epilepsy and controls) across cognitive, academic, clinical, and family factors.

Results

Disadvantage (ADI) was equally distributed between groups (p = .63). For CWE, high disadvantage was associated with lower overall intellectual quotient (IQ; p = .04), visual naming/expressive language (p = .03), phonemic (letter) fluency (p < .01), passive inattention (omission errors; p = .03), delayed verbal recall (p = .04), and dominant fine motor dexterity and speed (p < .01). Cognitive status of the HC group did not differ by level of disadvantage (p = .40). CWE exhibited greater academic difficulties in comparison to HC (p < .001), which were exacerbated by disadvantage in CWE (p = .02) but not HC (p < .05). High disadvantage was associated with a threefold risk for academic challenges prior to epilepsy onset (odds ratio = 3.31, p = .024).

Significance

Socioeconomic hardship (increased neighborhood disadvantage) exerts a significant adverse impact on the cognitive and academic status of youth with new and recent onset epilepsies, an impact that needs to be incorporated into etiological models of the neurobehavioral comorbidities of epilepsy.
Rate of crop‐weed hybridization in Sorghum bicolor × Sorghum halepense is influenced by genetic background, pollen load, and the environment
Authors: Sias Cynthia , Subramanian Nithya , Hodnett George , Rooney William , Bagavathiannan Muthukumar
Published: March 2023

The potential for gene flow between cultivated species and their weedy relatives poses agronomic and environmental concerns, particularly when there are opportunities for the transfer of adaptive or agronomic traits such as herbicide resistance into the weedy forms. Grain sorghum (Sorghum bicolor) is an important crop capable of interspecific hybridization with its weedy relative johnsongrass (Sorghum halepense). Previous findings have shown that triploid progenies resulting from S. bicolor × S. halepense crosses typically collapse with only a few developing into mature seeds, whereas tetraploids often fully develop. The objective of this experiment was to determine the impact of S. bicolor genotype and pollen competition on the frequency of hybridization between S. bicolor and S. halepense. A total of 12 different cytoplasmic male sterile S. bicolor genotypes were compared with their respective male fertile lines across 2 years, to assess the frequency of hybridization and seed set when S. halepense served as the pollinator parent. Results indicate significant differences in the frequency of interspecific hybridization among the S. bicolor genotypes, and pollen fertility in S. bicolor reduced the rate of this interspecific hybridization by up to two orders of magnitude. Further, hybridization rates greatly varied across the two study environments. Results are helpful for developing appropriate gene flow mitigation strategies and indicate that gene flow could be reduced by the selection of appropriate seed parents for sorghum hybrids.
Population structure and invasion history of Aedes aegypti (Diptera: Culicidae) in Southeast Asia and Australasia
Authors: Maynard Andrew J. , Ambrose Luke , Bangs Michael J. , Ahmad Rohani , Butafa Charles , Beebe Nigel W.
Published: March 2023

The dengue mosquito, Aedes aegypti (Linnaeus, 1762), is a highly invasive and medically significant vector of dengue, yellow fever, chikungunya and Zika viruses, whose global spread can be attributed to increased globalization in the 15th through 20th century. Records of the invasion history of Ae. aegypti across Southeast Asia are sparse and there is little knowledge regarding the invasion routes that the species exploited to gain a foothold in the Indo‐Pacific. Likewise, a broad and geographically thorough investigation of Ae. aegypti population genetics in the Indo‐Pacific is lacking, despite this region being highly impacted by diseases transmitted by this species. We assess 11 nuclear microsatellites and mitochondrial COI sequences, coupled with widespread sampling through the Indo‐Pacific region to characterise population structure at a broad geographic scale. We also perform a comprehensive literature search to collate documentation of the first known records of Ae. aegypti at various locations in the Indo‐Pacific. We revealed additional spatial population genetic structure of Ae. aegypti in Southeast Asia, the Indo‐Pacific and Australasia compared with previous studies and find differentiation between multiple Queensland and Torres Strait Islands populations. We also detected additional genetic breaks within Australia, Indonesia and Malaysia. Characterising the structure of previously unexplored populations through this region enhances the understanding of the population structure of Ae. aegypti in Australasia and Southeast Asia and may assist predictions of future mosquito movement, informing control strategies as well as assessing the risk of new invasion pathways.
The cascading effects of submerged macrophyte collapse on geese at Poyang Lake, China
Authors: Wang Yafang , Chen Qing , Li Lei , Ding Huifang , Fraser James D. , Hou Jinjin , Wang Wenjuan
Published: March 2023

Wetland habitat degradation has become more common in recent decades, leading to an increasing occurrence of food shortages for wild animals. Although the direct effects of food shortages on consumers have been well studied, the cascading effects on interspecific interactions remain poorly understood. Targeted research is required to improve our understanding of the impacts of food shortage on animals and to facilitate the development of conservation plans.

Here, we used DNA metabarcoding and field observations of goose foraging behaviour to assess the cascading effects of collapse of tubers of Vallisneria spp., the dominant submerged macrophytes at Poyang Lake, China, on the diet of the swan goose (Anser cygnoides) and on the interspecific competition among goose species, the swan goose, the bean goose (Anser fabalis), and the greater white‐fronted goose (Anser albifrons). The metabarcoding analyses were carried out on faecal samples collected in winter 2016/17 and 2018/19, and behavioural observations were conducted in winter 2021/22.

Our study elucidated the dietary compositions of the three goose species in greater detail than previously known. When Vallisneria tubers became rare, swan geese switched their foraging focus to Carex spp. and other grassland plants. When tuber abundance rebounded, swan geese resumed tuber foraging, suggesting the superiority of tubers as food for swan geese. Swan geese foraging on Carex, the major foods of bean geese and greater white‐fronted geese, potentially increased interspecific competition among goose species. Swan geese increased their pecking rates while bean geese increased time spent foraging apparently to cope with interspecific competition.

Given the severe impacts of tuber collapses on waterbirds and the important role of Poyang Lake in waterbird protection, we advocate restoring submerged macrophytes to provide high quality foods for tuber‐foraging waterbirds.

Our study emphasises that, in addition to directly influencing consumers, food collapses may also influence other species through changes in interspecific interactions. Our study also illustrates the importance of behavioural plasticity to cope with interspecific competition and to respond to environment change.
Neighbourhood landscape context shapes local species richness patterns across continents
Authors: Li Lihe , Teng Shuqing N. , Zhang Yong , Li Yuxiang , Wang Haijun , Santana Joana , Reino Luís , Abades Sabastián , Svenning Jens‐Christian , Xu Chi
Published: March 2023

Aim

Recent studies highlight the importance of linking landscape ecology and macroecology for a better understanding of broad‐scale biodiversity patterns. The “landscape context effect” denotes that species responses and biodiversity in a focal area are shaped by neighbouring landscape composition and structure outside the focal area. Here, we test whether the landscape context effect could be pronounced at macroecological scales.

Location

Sub‐Saharan Africa and continental China.

Time period

Late 20th to early 21st centuries.

Taxa studied

Terrestrial mammals (≥2 kg).

Methods

We calculated species richness on the basis of grid cells of 50 km × 50 km and 100 km × 100 km. We used ordinary least square and random forest models to examine the relationships between species richness within grid cells and landscape context (defined as composition and structure of the neighbouring landscape outside the grid cells, with distances of 10–400 km to the boundary of a given grid cell). We used variation partitioning to quantify the independent and shared explanatory power of the landscape context variables, grouping species by body size and diet.

Results

Landscape context alone explained ≤20% of the variation in species richness, even when controlling for correlations with macroenvironmental variables (climate, productivity and topography) and correlations with landscape attributes within the grid cells. Importantly, the explanatory power of landscape context at the scales of 100–400 km ofen outweighed grid‐cell landscape attributes or macro‐environmental variables. The independent explanatory power of landscape context was lowest for small‐sized omnivores. Furthermore, we found higher independent explanatory power for large herbivores in sub‐Saharan Africa than in continental China.

Main conclusions

Landscape context plays a substantial role in shaping local biodiversity patterns at regional and continental scales, with its strength varying with organism diet and movement needs and possibilities. These findings support that conservation efforts should include effective management of landscape structure, with attention to differing space requirements among organism groups. Our work also illustrates the scope for testing landscape ecological hypotheses at macroecological scales.
Whole genome sequencing reveals novel genetic mutations of Helicobacter pylori associating with resistance to clarithromycin and levofloxacin
Authors: Lyu Tao , Cheung Ka Shing , Deng Zijie , Ni Li , Chen Chuan , Wu Juan , Leung Wai K. , Seto Wai Kay
Published: March 2023

Background

Detection of mutations in one or a couple of genes may not provide enough data or cover all the genomic DNA variance related to antibiotic resistance of Helicobacter pylori to clarithromycin (CLA) and levofloxacin (LVX). We aimed to perform whole genome sequencing to explore novel antibiotic resistance‐related genes to increase predictive accuracy for future targeted sequencing tests.

Methods

Gastric mucosal biopsies were taken during upper endoscopy in 27 H. pylori‐infected patients. According to culture‐based antibacterial susceptibility test, H. pylori strains were divided into three groups, with nine strains in each group: CLA single‐drug resistance (group C), LVX single‐drug resistance (group L), and strains sensitive to all antibacterial drugs (group S). Based on whole genome sequencing with group S being the control, group C and group L group‐specific single nucleotide variants and amino acid mutations were screened, and potential candidate genes related to CLA and LVX resistance were identified.

Results

The median age of study subjects was 35 years (IQR: 31–40), and 17 (63.0%) were male. All nine CLA‐resistant strains had A2143G mutations in 23S rRNA, while none of nine sensitive strains had the mutation. Six of nine strains in group L and six of nine strains in group S had 87th or 91st mutation in gyrA. After comparing sequencing data of strains among the three groups, we identified five mutated positions belonging to four genes related to CLA resistance, and 31 mutated positions belonging to 20 genes related to LVX resistance. Novel genetic mutations were detected for CLA resistance (including fliJ and clpX) and LVX resistance (including fliJ, cheA, hemE, Val360Ile, and HP0568). Missense mutations in fliJ and cheA gene were mainly involved in chemotaxis and flagellar motility to facilitate bacterial escape of antibiotics, while the functions of other novel gene mutations underpinning antibiotic resistance remain to be investigated.

Conclusion

Whole genome sequencing detected potential novel genetic mutations conferring resistance of H. pylori to CLA and LVX including fliJ and cheA. Further studies to correlate these findings with treatment outcome should be performed.