bluuebunny/crossref_metadata_2025 huggingface dataset:
Introduction of the “Straight-Leg-Evaluation-Trauma-Test” as a rapid assessment for long-bone fractures in a trauma bay setting
Authors: Berk Till , Halvachizadeh Sascha , Bitzi Michelle , Kalbas Yannik , Colacicco Giovanni , Simmen Hans-Peter , Pape Hans-Christoph , Neuhaus Valentin
Published: August 2022

ABSTRACT

Purpose:

Lower extremity long bone fractures can constitute a substantial source of bleeding in the polytraumatized patient and should be diagnosed in the primary survey as fast as possible. Standardized clinical assessment tools for fracture detection in the trauma bay, however, are lacking. We propose the “Straight-Leg-Evaluation-Trauma-Test” (SILENT-test) as a rapid assesment tool for the lower extremity. The aim of this prospective diagnostic study was to evaluate the efficacy of this test in a standardized preclinical setting.

Methods:

Medical professionals with different levels of experience performed clinical fracture diagnotics in four human cadavers with two femur- and two tibia shaft fractures. The SILENT-test (ST) and conventional fracture testing (CS) were performed. A cross-over design was used and participants were randomly allocated and blinded. Accuracy, subjective clinical applicability, and clinical performance of both tests were measured and compared.

Results:

A total of 440 clinical tests were performed by 55 examiners. For femoral fractures, ST had a positive predictive value (PPV) of 0.97 (95% CI 0.93 to 0.99), a specificity of 0.91 (95% CI 0.80 to 0.97) and a sensitivity of 0.96 (95% CI 0.92 to 0.99). CS had a PPV of 0.97 (95% CI 0.93 to 0.99), a specificity of 0.93 (95% CI 0.82 to 0.98) and a sensitivity of 0.89 (95% CI 0.83 to 0.93). ST was significantly more feasible (8.05 ± 1.48 vs. 5.91 ± 2.09) had a significantly greater certainty (8.32 ± 1.84 vs. 7.89 ± 2.01) and was significantly faster (7.73 ± 6.61 vs 14.50 ± 11.11 s).

Conclusion:

Preclinical evaluation of the SILENT-test showed equal accuracy compared to conventional fracture testing, while being significantly faster and significantly more clinically applicable. Prospective diagnostic clinical studies are justified to hopfully improve trauma care.

Level of evidence:

Level III.

Highlights
Emergency laparoscopic cholecystectomy after cesarean section in pregnant women at 38 weeks: A clinical case
Authors: Son Tran Que , Ai Dang Quoc , Hung Tran Manh , Hoc Tran Hieu , Tuan Nguyen Minh , Van Truong Trieu , Van Kien Quach , Van Minh Nguyen , Minh Hue Bui Thi
Published: August 2022

ABSTRACT

Introduction:

Acute cholecystitis due to gallstone disease during pregnancy often requires emergency surgical treatment. Laparoscopic cholecystectomy (LC) can be performed concurrently with cesarean section when surgical management can be delayed until after birth.

Case presentation:

A 25-year-old female patient was 38 weeks pregnant. On day five, she was taken to the hospital to treat cholecystitis. We performed emergency surgery in collaboration with the obstetrician and gastrointestinal surgery team. A healthy baby weighing 3200 g was born with an Apgar score of 9–10. After the closure of the vertical incision, a pneumoperitoneum was established, and the gallbladder was removed laparoscopically. On the sixth postoperative day, the patient was discharged from the hospital without complications.

Discussion:

LC was performed immediately following cesarean delivery. The infant delivery diminished the size of the uterus, removing it from the surgical field. LC was thus performed in a safe, effective, and expeditious manner, providing a definitive treatment. Breastfeeding was unaffected because the patients had no dietary restrictions. The recoveries were uncomplicated, with better cosmetic results, short lengths of stay, and reasonable costs.

Conclusion:

Faster recovery, better cosmetic results, and better lactation outcomes are advantages of LC immediately after cesarean delivery.

Highlights
What is at Stake in the Frame Story? A Timurid Reshaping of the Romance of Bahrām Gūr
Authors: Toutant Marc
Published: August 2022

This article examines MīrʿAlī Shīr Navāʾī'sSabʿa-yi Sayyār(889/1484), a Chaghatay rewriting of Niẓāmī'sHaft Paykarand Amīr Khusraw Dihlavī'sHasht Bihisht.In the prologue of hismasnavī, the Timurid poet expresses harsh criticism against his Persian models. He targets his predecessors’ frame stories, and more specifically their depiction of Bahrām Gūr's behavior while listening to the seven nested narratives. In fact, Navāʾī's reshaping of the poem epitomizes several Timurid trends with regard to the Persianate cultural complex: a tendency toward standardization, as well as a keen interest in Naqshbandī Sufism. Incidentally, the latter aspect shows Jāmī's influence on the Chaghatay polymath's literary output.
Effects of multiple stressors in fish: how parasites and contaminants interact
Authors: Sures Bernd , Nachev Milen
Published: August 2022

Interest in local environmental conditions and the occurrence and behaviour of parasites has increased over the last 3 decades, leading to the discipline of Environmental Parasitology. The aim of this discipline is to investigate how anthropogenically altered environmental factors influence the occurrence of parasites and how the combined effects of pollutants and parasites affect the health of their hosts. Accordingly, in this paper, we provide an overview of the direct and indirect effects of pollutants on the occurrence and distribution of fish parasites. However, based on current knowledge, it is difficult to draw general conclusions about these interdependencies, as the effects of pollutants on free-living (larval) parasite stages, as well as their effects on ectoparasites, depend on the pollutant–host–parasite combination as well as on other environmental factors that can modulate the harmful effects of pollutants. Furthermore, the question of the combined effects of the simultaneous occurrence of parasites and pollutants on the physiology and health of the fish hosts is of interest. For this purpose, we differentiate between the dominance effects of individual stressors over other, additive or synergistically reinforcing effects as well as combined antagonistic effects. For the latter, there are only very few studies, most of which were also carried out on invertebrates, so that this field of research presents itself as very promising for future investigations.
Post-traumatic growth amongst UK armed forces personnel who were deployed to Afghanistan and the role of combat injury, mental health and pain: the ADVANCE cohort study
Authors: Dyball Daniel , Bennett Alexander N. , Schofield Susie , Cullinan Paul , Boos Christopher J. , Bull Anthony M. J. , Stevelink Sharon A. M. , Fear Nicola T.
Published: August 2022

Background

Post-traumatic growth (PTG) is a positive psychological consequence of trauma. The aims of this study were to investigate whether combat injury was associated with deployment-related PTG in a cohort of UK military personnel who were deployed to Afghanistan, and whether post-traumatic stress disorder (PTSD), depression and pain mediate this relationship.

Methods

521 physically injured (n = 138 amputation; n = 383 non-amputation injury) and 514 frequency-matched uninjured personnel completed questionnaires including the deployment-related Post-Traumatic Growth Inventory (DPTGI). DPTGI scores were categorised into tertiles of: no/low (score 0–20), moderate (score 21–34) or a large (35–63) degree of deployment-related PTG. Analysis was completed using generalised structural equation modelling.

Results

A large degree of PTG was reported by 28.0% (n = 140) of the uninjured group, 36.9% (n = 196) of the overall injured group, 45.4% (n = 62) of amputee and 34.1% (n = 134) of the non-amputee injured subgroups. Combat injury had a direct effect on reporting a large degree of PTG [Relative risk ratio (RRR) 1.59 (95% confidence interval (CI) 1.17–2.17)] compared to sustaining no injury. Amputation injuries also had a significant direct effect [RRR 2.18 (95% CI 1.24–3.75)], but non-amputation injuries did not [RRR 1.35 (95% CI 0.92–1.93)]. PTSD, depression and pain partially mediate this relationship, though mediation differed depending on the injury subtype. PTSD had a curvilinear relationship with PTG, whilst depression had a negative association and pain had a positive association.

Conclusions

Combat injury, in particular injury resulting in traumatic amputation, is associated with reporting a large degree of PTG.
Dynamic tracking effect of a magnetic navigated dual hemisphere capsule robot
Authors: Zhang Yongshun , Liu Xu , Liu Zhenhu , Zhao Zihao , Dong Hai , Wang Dianlong
Published: August 2022

For diagnostic and therapeutic applications in spacious spots of the gastrointestinal (GI) tract, the single rigid body capsule clinically applied is difficult to realize the fix-point posture adjustment function manipulated by the external permanent magnet system using the static balance control because the posture alignment and the locomotion interfere with each other. To realize this function easily, the dual hemisphere capsule robot (DHCR) is proposed, based on tracking effect—the axis of DHCR keeps tracking the normal orientation of the spatial universal rotating magnetic vector (SURMV). Since tracking effect employs dynamic balance control, dynamic stability of the DHCR system affects posture alignment performance. This paper focuses on posture alignment dynamic modeling and the influence of the magnetic flux density and the angular velocity of the SURMV, along with the damping coefficient of the GI tract surface on stability, obtaining the stability domains of parameters. Furthermore, to reduce error due to the uncertainties in complex GI tract environment, the sliding mode controller based on nominal model is proposed to achieve more accurate dynamic tracking, and Lyapunov theorem is employed to assess stability of controller. Finally, the tracking effect is verified through simulations and experiments, indicating that the fix-point posture adjustment can be realized with higher accuracy and efficiency.
Long-term object search using incremental scene graph updating
Authors: Zhou Fangbo , Liu Huaping , Zhao Huailin , Liang Lanjun
Published: August 2022

Effective searching for target objects in indoor scenes is essential for household robots to perform daily tasks. With the establishment of a precise map, the robot can navigate to a fixed static target. However, it is difficult for mobile robots to find movable objects like cups. To address this problem, we establish an object search framework that combines navigation map, semantic map, and scene graph. The robot updates the scene graph to achieve a long-term target search. Considering the different start positions of the robots, we weigh the distance the robot walks and the probability of finding objects to achieve global path planning. The robot can continuously update the scene graph in a dynamic environment to memorize the position relation of objects in the scene. This method has been realized in both simulation and real-world environments. The experimental results show the feasibility and effectiveness of this method.
Institutional transition from invasive to non-invasive imaging in children with univentricular heart defects: safety and cost savings
Authors: Yanovskiy Anna , Martelius Laura , Rahkonen Otto , Pihkala Jaana , Happonen Juha-Matti , Boldt Talvikki , Jaakkola Ilkka , Peltonen Juha , Kortesniemi Mika , Mattila Ilkka , Ojala Tiina
Published: August 2022

Objectives:

Patients with univentricular heart defects require lifelong imaging surveillance. Recent advances in non-invasive imaging have enabled replacing these patients’ routine catheterisation. Our objective was to describe the safety and cost savings of transition of a tertiary care children’s hospital from routine invasive to routine non-invasive imaging of low-risk patients with univentricular heart defects.

Methods:

This single-centre cohort study consists of 1) a retrospective analysis of the transition from cardiac catheterisation (n = 21) to CT angiography (n = 20) before bidirectional Glenn operation and 2) a prospective study (n = 89) describing cardiac magnetic resonance before and after the total cavopulmonary connection in low-risk patients with univentricular heart defects.

Results:

Pre-Glenn: The total length of CT angiography was markedly shorter compared to the catheterisation: 30 min (range: 20–60) and 125 min (range: 70–220), respectively (p < 0.001). Catheterisation used more iodine contrast agents than CT angiography, 19 ± 3.9 ml, and 10 ± 2.4 ml, respectively (p < 0.001). Controlled ventilation was used for all catheterised and 3 (15%) CT angiography patients (p < 0.001). No complications occurred during CT angiography, while they emerged in 19% (4/21) catheterisation cases (p < 0.001). CT angiography and catheterisation showed no significant difference in the radiation exposure. Pre-/post-total cavopulmonary connection: All cardiac magnetic resonance studies were successful, and no complications occurred. In 60% of the cardiac magnetic resonance (53/89), no sedation was performed, and peripheral venous pressure was measured in all cases. Cost analysis suggests that moving to non-invasive imaging yielded cost savings of at least €2500–4000 per patient.

Conclusion:

Transition from routine invasive to routine non-invasive pre-and post-operative imaging is safely achievable with cost savings.
Tom Erbe Interviewed by Theodore Gordon
Authors: Erbe Tom , Gordon Theodore
Published: August 2022

In this interview, Tom Erbe reflects on his three decades as a developer of computer music software and hardware, both freeware and commercial. Tom met with Theodore Gordon on 8 December 2021 and discussed the beginnings of SoundHack and its roots in experimental music studio practice and hacker culture, ideas behind the design of sound processor interface and the shift from experimental software development to Eurorack modular hardware design.
The Modular Journey: Uncovering analogue aesthetics in digital landscapes
Authors: Kitzmann Andreas , Thorén Claes
Published: August 2022

This article draws on a practice theory perspective to investigate instances of sound practice in a particular community of technology use by focusing on the community and product offerings in and around contemporary modular synthesisers and their growing popularity in the ‘Eurorack’ format in order to investigate the attraction and allure of analogue things in a digital age. This article identifies issues of authenticity, legitimacy and creativity as key drivers of the way we project our identities onto objects and the intimate technologies we own, and the search for meaningful technological encounters. In the realm of sound practice, the follow-up questions are similar: why when there is software and affordable digital alternatives, do some musicians swear by modular synthesis given the commitment this practice requires in terms of money, time, self-education and exploration (and for a lack of a better term) tinkering? With Eurorack as a case study, this article investigates the attraction and allure of analogue things in a digital age by investigating meaningful sound practice as emerging out of the discourses of online communities around the modular synth phenomenon.
Two countries, similar practices: the political practices of the food industry influencing the adoption of key public health nutrition policies in Guatemala and Panama
Authors: Kroker-Lobos Maria F , Morales Lourdes Analí , Ramírez-Zea Manuel , Vandevijvere Stefanie , Champagne Beatriz , Mialon Melissa
Published: August 2022

Objective:

To identify the corporate political activity (CPA) strategies used by food industry actors during the development of two public health nutrition policies in Central America: Law #570 (taxation of sugar-sweetened beverages) in Panama and Bill #5504 (labelling and food marketing regulations) in Guatemala.

Design:

We triangulated data from publicly available information from 2018 to 2020, (e.g. industry and government materials; social media material) with semi-structured interviews with key stakeholders.

Setting:

Guatemala and Panama.

Participants:

Government, academia and international organisations workers in health and nutrition.

Design:

CPA strategies were categorised according to an existing internationally used taxonomy into action-based, instrumental strategies (coalition management, information management, direct involvement and influence in policy, legal action) and discursive strategies.

Results:

Instrumental strategies included the establishment of relationships with policymakers and direct lobbying against the proposed public policies. Discursive strategies were mainly criticising on the unfounded ground that they lacked evidence of effectiveness and will imply negative impacts on the economy. The industry pointed at individuals for making their own food choices, in order to shift the focus away from the role of its products in contributing to ill health.

Conclusion:

We provide evidence of the political practices used by the food industry to interfere with the development and implementation of public health nutrition policies to improve diets in Central America. Policymakers, public health advocates and the public should be informed about those practices and develop counterstrategies and arguments to protect the public and policies from the vested interests of the food industry.
Moisture and Seasonality Shifts Recorded in Holocene and Pleistocene Speleothems From Southeastern Arabia
Authors: Fleitmann D. , Burns S. J. , Matter A. , Cheng H. , Affolter S.
Published: August 2022

The source and seasonality of rainfall in southern Arabia during the early‐ to mid‐Holocene and preceding humid periods are controversial because fossil lacustrine sediments provide solely indirect information on the amount of rainfall. Hydrogen and oxygen isotope measurements on fluid inclusion water trapped in Holocene and Pleistocene stalagmites from Hoti Cave in Northern Oman are direct indicators of the isotopic composition of paleoprecipitation. Isotope values of fluid inclusions formed during peak interglacial periods plot along monsoonal water lines and are indicative of a southern monsoonal moisture source. The last monsoon‐dominated period lasting from ∼10,100 to 6,300 years before present was terminated within a few decades in southeastern Arabia. The subsequent reduction in rainfall amount and change from predominantly summer to predominantly winter rainfall had a profound impact on human communities living in this area and triggered migration from inland to coastal areas where resources were more abundant.
Argo Reveals the Scales and Provenance of Equatorial Island Upwelling Systems
Authors: Karnauskas Kristopher B. , Giglio Donata
Published: August 2022

Equatorial islands have distinct oceanographic signatures, including cool sea surface temperature and high productivity immediately to their west. It has long been hypothesized that topographic upwelling is responsible for such characteristics—upward deflection by the islands of the eastward‐flowing equatorial undercurrent (EUC). Using 22 years of in situ measurements by Argo, we provide the first direct observations of this process occurring with consistency at two prominent archipelagos in the equatorial Pacific. Argo measurements resolve a clear subsurface thermal fingerprint of vertical divergence at the depth of the EUC, confined to within 100 km of both the Gilbert (∼175°E) and Galápagos Islands (∼90°W). This signal at the Galápagos is well‐reproduced by a high‐resolution ocean reanalysis, enabling the estimation of vertical velocities balancing the zonal convergence of the EUC upon the islands. This sharpened view of the physics underpinning such important tropical ecosystems has implications for strategies to model and predict them.
Southern Control of Interhemispheric Synergy on Glacial Marine Carbon Sequestration
Authors: Du Jinlong , Ye Ying , Zhang Xu , Völker Christoph , Tian Jun
Published: August 2022

Among mechanisms accounting for atmospheric pCO2 drawdown during glacial periods, processes operating in the North Atlantic (NA) and Southern Ocean (SO) have been proposed to be critical. Their individual and synergic effects during a course of glaciation, however, remain enigmatic. We conducted simulations to examine these effects at idealized glacial stages. Under early‐glacial‐like conditions, cooling in the SO can trigger an initial pCO2 drawdown while the associated sea ice expansion has little impact on air‐sea gas exchange. Under later glacial‐like conditions, further cooling in the NA enhances ocean carbon uptake due to a stronger solubility pump, and the SO‐induced stronger deep stratification prevents carbon exchange between the deep and upper ocean. Meanwhile, strengthened dust deposition increases the SO contribution to the global biological pump, and CO2 outgassing is suppressed by fully extended sea ice cover. More carbon is then stored in the deep Pacific, acting as a passive reservoir.
Partitioning of Iron Between Liquid and Crystalline Phases of (Mg,Fe)O
Authors: Braithwaite James , Stixrude Lars
Published: August 2022

The density contrast between crystals and coexisting liquids is key to understanding the evolution of the magma ocean. While crystals remain denser than isochemical liquids in most oxide and silicate systems over the pressure range of Earth's mantle, element partitioning, particularly of abundant heavy elements such as iron, can alter the buoyancy. We use molecular dynamics simulations based on spin‐polarized density functional theory and adiabatic switching to determine the free energy of iron substitution in liquid and crystalline (Mg,Fe)O and the distribution coefficient. We find that iron is strongly incompatible with a distribution coefficient less than 0.3 over the mantle pressure range. We find that the crystal is buoyant with respect to coexisting liquid at pressures exceeding 50 GPa. The high‐spin to low‐spin transition has an important influence on the distribution coefficient, which decreases with increasing pressure up to 80 GPa, and then increases on further increase of pressure.
The Summertime Pacific‐North American Weather Regimes and Their Predictability
Authors: Nabizadeh Ebrahim , Lubis Sandro W. , Hassanzadeh Pedram
Published: August 2022

The forecast skill of numerical weather prediction (NWP) models and the intrinsic predictability can be different among weather regimes. Here, we examine the predictability of distinct Pacific‐North American weather regimes during extended boreal summer. The four identified weather regimes include Pacific trough, Arctic low, Arctic high, and Alaskan ridge. The medium range forecast skill of these regimes is quantified in the ECMWF and the National Centers for Environmental Prediction models from the TIGGE project. Based on anomaly correlation coefficient, persistence, and transition frequency, the highest forecast skill is consistently found for the Arctic high regime. Based on the instantaneous local dimension and persistence from a dynamical systems analysis, the Arctic high regime has the highest intrinsic predictability. The analysis also suggests that overall, the Pacific trough regime has the lowest intrinsic predictability. These findings are consistent with the forecast skills of the NWP models, and highlight the link between prediction skill and intrinsic predictability.
Hydroxychloride‐Bearing Fluid Inclusions in Ultramafic Rocks From New Caledonia: Implications for Serpentinization in Saline Environments on Earth and Beyond
Authors: Zhang Long , Wang Qiang , Mikhailenko Denis S. , Ding Xing , Li Wan‐Cai , Xian Haiyang
Published: August 2022

Serpentinization produces H2 and synthesizes CH4 that can support nonphotosynthetic habitability on Earth and possibly beyond. Although fluids on Earth and beyond that may participate in serpentinization are extensively saline with elevated levels of chlorine, chloride minerals are generally not considered to be a crucial component of serpentinization. In this study, we report the formation of kuliginite, a recently discovered hydroxychloride mineral with the ideal formula of Fe3Mg(OH)6Cl2, during internal serpentinization within olivine‐hosted fluid inclusions in ultramafic rocks from New Caledonia, southwest Pacific. It is inferred that kuliginite may form during serpentinization by Cl‐rich saline fluids under certain conditions on celestial bodies, which is largely unrevealed due to our insufficient knowledge about kuliginite. As a mineral containing ∼57 wt.% FeO that is mainly ferrous, kuliginite, even in minor amounts, may play an important role in iron partitioning during serpentinization, with a great influence on the production of H2 and synthesis of CH4. In a word, stabilization of kuliginite retards iron oxidation, whereas further hydration of kuliginite supplements canonical pathways of iron oxidation. In addition, as a hydroxychloride, kuliginite may have a significant weight in the chlorine budget of serpentinite. Therefore, kuliginite in the serpentinized fluid inclusions presented in this study may have general implications for serpentinization in certain saline environments on Earth and beyond, which needs to be further explored in the future.
Neurometabolic changes in neonates with congenital heart defects and their relation to neurodevelopmental outcome
Authors: Steger Céline , Feldmann Maria , Borns Julia , Hagmann Cornelia , Latal Beatrice , Held Ulrike , Jakab András , O’Gorman Tuura Ruth , Knirsch Walter
Published: August 2022

Background

Altered neurometabolite ratios in neonates undergoing cardiac surgery for congenital heart defects (CHD) may serve as a biomarker for altered brain development and neurodevelopment (ND).

Methods

We analyzed single voxel 3T PRESS H1-MRS data, acquired unilaterally in the left basal ganglia and white matter of 88 CHD neonates before and/or after neonatal cardiac surgery and 30 healthy controls. Metabolite ratios to Creatine (Cr) included glutamate (Glu/Cr), myo-Inositol (mI/Cr), glutamate and glutamine (Glx/Cr), and lactate (Lac/Cr). In addition, the developmental marker N-acetylaspartate to choline (NAA/Cho) was evaluated. All children underwent ND outcome testing using the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III) at 1 year of age.

Results

White matter NAA/Cho ratios were lower in CHD neonates compared to healthy controls (group beta estimate: −0.26, std. error 0.07, 95% CI: −0.40 – 0.13,pvalue <0.001, FDR correctedpvalue = 0.010). We found no correlation between pre- or postoperative white matter NAA/Cho with ND outcome while controlling for socioeconomic status and CHD diagnosis.

Conclusion

Reduced white matter NAA/Cho in CHD neonates undergoing cardiac surgery may reflect a delay in brain maturation. Further long-term MRS studies are needed to improve our understanding of the clinical impact of altered metabolites on brain development and outcome.

Impact

NAA/Cho was reduced in the white matter, but not the gray matter of CHD neonates compared to healthy controls.

No correlation to the 1-year neurodevelopmental outcome (Bayley-III) was found.

While the rapid change of NAA/Cho with age might make it a sensitive marker for a delay in brain maturation, the relationship to neurodevelopmental outcome requires further investigation.
Australian arm of the International Spinal Cord Injury (Aus-InSCI) Community Survey: 3. Drivers of quality of life in people with spinal cord injury
Authors: Kifley Annette , Arora Mohit , Nunn Andrew , Marshall Ruth , Geraghty Timothy , Weber Gerard , Urquhart Sue , Craig Ashley , Cameron Ian D. , Middleton James W.
Published: August 2022

Study design

Cross-sectional population-based survey for the Australian cohort of the International Spinal Cord Injury (InSCI) Community Survey.

Objectives

To differentiate subgroups of people with spinal cord injury (SCI) who self-report good and poor overall quality of life (QoL) using domains of the International Classification of Functioning (ICF), and to evaluate how these factors contribute to QoL when considered together, while controlling confounders.

Setting

Australian survey data from four state-wide SCI services, one government insurance agency, and three not-for-profit consumer organisations.

Methods

Explanatory factors for QoL were compared between participants reporting poor vs. good QoL. Path models estimated total, direct and mediated contributions from each explanatory factor to QoL ratings after accounting for confounders.

Results

Most participants (62%) reported good or very good QoL, 12% reported poor or very poor QoL. When explanatory factors were considered together, the strongest total effects on QoL involved social integration (+0.36 SDs), subjective social position (+0.29), secondary health condition burden (−0.28), activity/participation problem burden (−0.26), day-to-day assistance (−0.26), mental health (+0.18), pain (−0.16), self-efficacy (+0.15), vitality (+0.14) and environmental barriers (−0.11). Effects of social integration, mental health, vitality, self-efficacy, pain and activity/participation problems were partly or wholly direct.

Conclusion

Opportunities to improve QoL in people with SCI exist at every level of the health system. Virtually all aspects of the ICF framework make a substantive difference to QoL outcomes. Social and psychological factors and ability to complete desired activities have key direct effects and influence effects of secondary health condition burden and environmental barriers.
A single WNT enhancer drives specification and regeneration of the Drosophila wing
Authors: Gracia-Latorre Elena , Pérez Lidia , Muzzopappa Mariana , Milán Marco
Published: August 2022

Wings have provided an evolutionary advantage to insects and have allowed them to diversify. Here, we have identified in Drosophila a highly robust regulatory mechanism that ensures the specification and growth of the wing not only during normal development but also under stress conditions. We present evidence that a single wing-specific enhancer in the wingless gene is used in two consecutive developmental stages to first drive wing specification and then contribute to mediating the remarkable regenerative capacity of the developing wing upon injury. We identify two evolutionary conserved cis-regulatory modules within this enhancer that are utilized in a redundant manner to mediate these two activities through the use of distinct molecular mechanisms. Whereas Hedgehog and EGFR signalling regulate Wingless expression in early primordia, thus inducing wing specification from body wall precursors, JNK activation in injured tissues induce Wingless expression to promote compensatory proliferation. These results point to evolutionarily linked conservation of wing specification and regeneration to ensure robust development of the wing, perhaps the most relevant evolutionary novelty in insects.
Population-based tract-to-region connectome of the human brain and its hierarchical topology
Authors: Yeh Fang-Cheng
Published: August 2022

Connectome maps region-to-region connectivities but does not inform which white matter pathways form the connections. Here we constructed a population-based tract-to-region connectome to fill this information gap. The constructed connectome quantifies the population probability of a white matter tract innervating a cortical region. The results show that ~85% of the tract-to-region connectome entries are consistent across individuals, whereas the remaining (~15%) have substantial individual differences requiring individualized mapping. Further hierarchical clustering on cortical regions revealed dorsal, ventral, and limbic networks based on the tract-to-region connective patterns. The clustering results on white matter bundles revealed the categorization of fiber bundle systems in the association pathways. This tract-to-region connectome provides insights into the connective topology between cortical regions and white matter bundles. The derived hierarchical relation further offers a categorization of gray and white matter structures.
Epigenome-wide association study of human frontal cortex identifies differential methylation in Lewy body pathology
Authors: Pihlstrøm Lasse , Shireby Gemma , Geut Hanneke , Henriksen Sandra Pilar , Rozemuller Annemieke J. M. , Tunold Jon-Anders , Hannon Eilis , Francis Paul , Thomas Alan J. , Love Seth , Mill Jonathan , van de Berg Wilma D. J. , Toft Mathias
Published: August 2022

Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are closely related progressive disorders with no available disease-modifying therapy, neuropathologically characterized by intraneuronal aggregates of misfolded α-synuclein. To explore the role of DNA methylation changes in PD and DLB pathogenesis, we performed an epigenome-wide association study (EWAS) of 322 postmortem frontal cortex samples and replicated results in an independent set of 200 donors. We report novel differentially methylated replicating loci associated with Braak Lewy body stage near TMCC2, SFMBT2, AKAP6 and PHYHIP. Differentially methylated probes were independent of known PD genetic risk alleles. Meta-analysis provided suggestive evidence for a differentially methylated locus within the chromosomal region affected by the PD-associated 22q11.2 deletion. Our findings elucidate novel disease pathways in PD and DLB and generate hypotheses for future molecular studies of Lewy body pathology.
Single cell transcriptomic analysis of the immune cell compartment in the human small intestine and in Celiac disease
Authors: Atlasy Nader , Bujko Anna , Bækkevold Espen S. , Brazda Peter , Janssen-Megens Eva , Lundin Knut E. A. , Jahnsen Jørgen , Jahnsen Frode L. , Stunnenberg Hendrik G.
Published: August 2022

Celiac disease is an autoimmune disorder in which ingestion of dietary gluten triggers an immune reaction in the small intestine leading to destruction of the lining epithelium. Current treatment focusses on lifelong adherence to a gluten-free diet. Gluten-specific CD4+ T cells and cytotoxic intraepithelial CD8+ T cells have been proposed to be central in disease pathogenesis. Here we use unbiased single-cell RNA-sequencing and explore the heterogeneity of CD45+ immune cells in the human small intestine. We show altered myeloid cell transcriptomes present in active celiac lesions. CD4+ and CD8+ T cells transcriptomes show extensive changes and we define a natural intraepithelial lymphocyte population that is reduced in celiac disease. We show that the immune landscape in Celiac patients on a gluten-free diet is only partially restored compared to control samples. Altogether, we provide a single cell transcriptomic resource that can inform the immune landscape of the small intestine during Celiac disease.
Cavity-enhanced field-resolved spectroscopy
Authors: Sulzer Philipp , Högner Maximilian , Raab Ann-Kathrin , Fürst Lukas , Fill Ernst , Gerz Daniel , Hofer Christina , Voronina Liudmila , Pupeza Ioachim
Published: August 2022

Femtosecond enhancement cavities1 are key to applications including high-sensitivity linear2–4 and nonlinear5,6 gas spectroscopy, as well as efficient nonlinear optical frequency conversion7–10. Yet, to date, the broadest simultaneously enhanced bandwidths amount to <20% of the central optical frequency8,9,11–15. Here, we present an ultrabroadband femtosecond enhancement cavity comprising gold-coated mirrors and a wedged-diamond-plate input coupler, with an average finesse of 55 for optical frequencies below 40 THz and exceeding 40 in the 120–300 THz range. Resonant enhancement of a 50-MHz-repetition-rate offset-free frequency comb spanning 22–40 THz results in a waveform-stable ultrashort circulating pulse with a spectrum supporting a Fourier limit of 1.6 cycles, enabling time-domain electric-field-resolved spectroscopy of molecular samples with temporally separated excitation and molecular response16. The contrast between the two is improved by taking advantage of destructive interference at the input coupler. At an effective interaction length with a gas of up to 81 m, this concept promises parts-per-trillion-level ultrabroadband electric-field-resolved linear and nonlinear spectroscopy of impulsively excited molecular vibrations.
Gene–environment correlations across geographic regions affect genome-wide association studies
Authors: Abdellaoui Abdel , Dolan Conor V. , Verweij Karin J. H. , Nivard Michel G.
Published: August 2022

Gene–environment correlations affect associations between genetic variants and complex traits in genome-wide association studies (GWASs). Here we showed in up to 43,516 British siblings that educational attainment polygenic scores capture gene–environment correlations, and that migration extends these gene–environment correlations beyond the family to broader geographic regions. We then ran GWASs on 56 complex traits in up to 254,387 British individuals. Controlling for geographic regions significantly decreased the heritability for socioeconomic status (SES)-related traits, most strongly for educational attainment and income. For most traits, controlling for regions significantly reduced genetic correlations with educational attainment and income, most significantly for body mass index/body fat, sedentary behavior and substance use, consistent with gene–environment correlations related to regional socio-economic differences. The effects of controlling for birthplace and current address suggest both passive and active sources of gene–environment correlations. Our results show that the geographic clustering of DNA and SES introduces gene–environment correlations that affect GWAS results.
Artificial intelligence-enabled detection and assessment of Parkinson’s disease using nocturnal breathing signals
Authors: Yang Yuzhe , Yuan Yuan , Zhang Guo , Wang Hao , Chen Ying-Cong , Liu Yingcheng , Tarolli Christopher G. , Crepeau Daniel , Bukartyk Jan , Junna Mithri R. , Videnovic Aleksandar , Ellis Terry D. , Lipford Melissa C. , Dorsey Ray , Katabi Dina
Published: August 2022

There are currently no effective biomarkers for diagnosing Parkinson’s disease (PD) or tracking its progression. Here, we developed an artificial intelligence (AI) model to detect PD and track its progression from nocturnal breathing signals. The model was evaluated on a large dataset comprising 7,671 individuals, using data from several hospitals in the United States, as well as multiple public datasets. The AI model can detect PD with an area-under-the-curve of 0.90 and 0.85 on held-out and external test sets, respectively. The AI model can also estimate PD severity and progression in accordance with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (R = 0.94,P = 3.6 × 10–25). The AI model uses an attention layer that allows for interpreting its predictions with respect to sleep and electroencephalogram. Moreover, the model can assess PD in the home setting in a touchless manner, by extracting breathing from radio waves that bounce off a person’s body during sleep. Our study demonstrates the feasibility of objective, noninvasive, at-home assessment of PD, and also provides initial evidence that this AI model may be useful for risk assessment before clinical diagnosis.
Atezolizumab versus chemotherapy in advanced or metastatic NSCLC with high blood-based tumor mutational burden: primary analysis of BFAST cohort C randomized phase 3 trial
Authors: Peters Solange , Dziadziuszko Rafal , Morabito Alessandro , Felip Enriqueta , Gadgeel Shirish M. , Cheema Parneet , Cobo Manuel , Andric Zoran , Barrios Carlos H. , Yamaguchi Masafumi , Dansin Eric , Danchaivijitr Pongwut , Johnson Melissa , Novello Silvia , Mathisen Michael S. , Shagan Sarah M. , Schleifman Erica , Wang Jin , Yan Mark , Mocci Simonetta , Voong David , Fabrizio David A. , Shames David S. , Riehl Todd , Gandara David R. , Mok Tony
Published: August 2022

Tumor mutational burden (TMB) is being explored as a predictive biomarker for cancer immunotherapy outcomes in non-small cell lung cancer. BFAST (NCT03178552)—an open-label, global, multicohort trial—evaluated the safety and efficacy of first-line targeted therapies or immunotherapy in patients with unresectable Stage IIIB or IV advanced or metastatic non-small cell lung cancer who were selected for biomarker status using blood-based targeted next-generation sequencing. In the Phase 3 cohort C evaluating blood-based (b)TMB as a biomarker of atezolizumab efficacy, patients with bTMB of ≥10 (N = 471) were randomized 1:1 to receive atezolizumab or platinum-based chemotherapy per local standard of care. Cohort C did not meet its primary endpoint of investigator-assessed progression-free survival in the population with bTMB of ≥16 (hazard ratio, 0.77; 95% confidence interval: 0.59, 1.00; P = 0.053). Adverse events leading to treatment withdrawal occurred in 10% of patients in the atezolizumab arm and 20% in the chemotherapy arm. Adverse events of special interest occurred in 42% of patients in the atezolizumab arm and 26% in the chemotherapy arm. A prespecified exploratory analysis compared the bTMB clinical trial assay with the FoundationOne Liquid Companion Diagnostic assay and showed high concordance between assays. Additional exploration of bTMB to identify optimal cutoffs, confounding factors, assay improvements or cooperative biomarkers is warranted.
Neutralization titer biomarker for antibody-mediated prevention of HIV-1 acquisition
Authors: Gilbert Peter B. , Huang Yunda , deCamp Allan C. , Karuna Shelly , Zhang Yuanyuan , Magaret Craig A. , Giorgi Elena E. , Korber Bette , Edlefsen Paul T. , Rossenkhan Raabya , Juraska Michal , Rudnicki Erika , Kochar Nidhi , Huang Ying , Carpp Lindsay N. , Barouch Dan H. , Mkhize Nonhlanhla N. , Hermanus Tandile , Kgagudi Prudence , Bekker Valerie , Kaldine Haajira , Mapengo Rutendo E. , Eaton Amanda , Domin Elize , West Carley , Feng Wenhong , Tang Haili , Seaton Kelly E. , Heptinstall Jack , Brackett Caroline , Chiong Kelvin , Tomaras Georgia D. , Andrew Philip , Mayer Bryan T. , Reeves Daniel B. , Sobieszczyk Magdalena E. , Garrett Nigel , Sanchez Jorge , Gay Cynthia , Makhema Joseph , Williamson Carolyn , Mullins James I. , Hural John , Cohen Myron S. , Corey Lawrence , Montefiori David C. , Morris Lynn
Published: August 2022

The Antibody Mediated Prevention trials showed that the broadly neutralizing antibody (bnAb) VRC01 prevented acquisition of human immunodeficiency virus-1 (HIV-1) sensitive to VRC01. Using AMP trial data, here we show that the predicted serum neutralization 80% inhibitory dilution titer (PT80) biomarker—which quantifies the neutralization potency of antibodies in an individual’s serum against an HIV-1 isolate—can be used to predict HIV-1 prevention efficacy. Similar to the results of nonhuman primate studies, an average PT80 of 200 (meaning a bnAb concentration 200-fold higher than that required to reduce infection by 80% in vitro) against a population of probable exposing viruses was estimated to be required for 90% prevention efficacy against acquisition of these viruses. Based on this result, we suggest that the goal of sustained PT80 >200 against 90% of circulating viruses can be achieved by promising bnAb regimens engineered for long half-lives. We propose the PT80 biomarker as a surrogate endpoint for evaluation of bnAb regimens, and as a tool for benchmarking candidate bnAb-inducing vaccines.
The relationship between antithrombin administration and inflammation during veno-venous ECMO
Authors: Panigada Mauro , Spinelli Elena , De Falco Stefano , Consonni Dario , Novembrino Cristina , Boscolo Anzoletti Massimo , Panarello Giovanna , Occhipinti Giovanna , dos Santos Claudia C. , Pesenti Antonio , Arcadipane Antonio , Grasselli Giacomo
Published: August 2022

Veno-venous Extracorporeal Membrane Oxygenation (ECMO) is used in the most severe cases of respiratory failure and further exacerbates the patients’ inflammatory status. Antithrombin is supplemented during ECMO for its anticoagulant effects, but it also deploys anti-inflammatory properties. In this pre-specified ancillary study of the GATRA trial [NCT03208270] we aimed to evaluate the relationship between antithrombin and inflammation during ECMO. Forty-six patients were included in the study, 23 were randomized to receive antithrombin to maintain a level of 80–120% (study group) and 23 were randomized not to be supplemented (control group). Anticoagulation was provided in both groups with heparin infusion. Six cytokines were measured at 5 timepoints from prior to ECMO start to 7 days after ECMO removal. Cytokines decreased during the study but overall were not very different in the two groups. Testing the interaction between the study group and timepoints suggests that the administration of antithrombin led to a more rapid decrease over time of IL-6, IL-1β, TNF-⍺ and Pro-ADM. Plasma levels of antithrombin (either endogenous or exogenous) were negatively associated with all cytokines. Inflammation decreases during ECMO but a causal effect of antithrombin administration on the reduction of inflammation (and its clinical relevance) must be confirmed by appropriately powered studies.
Time estimation and arousal responses in dopa-responsive dystonia
Authors: Becker Leonie F. , Tunc Sinem , Murphy Peter , Bäumer Tobias , Weissbach Anne , Pauly Martje G. , Al-Shorafat Duha M. , Saranza Gerard , Lang Anthony E. , Beste Christian , Donner Tobias H. , Verrel Julius , Münchau Alexander
Published: August 2022

Dopa-responsive dystonia (DRD) is caused by an impaired dopamine biosynthesis due to a GTP-cyclohydrolase-1 (GCH1) deficiency, resulting in a combination of dystonia and parkinsonism. However, the effect of GCH1 mutations and levodopa treatment on motor control beyond simple movements, such as timing, action preparation and feedback processing, have not been investigated so far. In an active time estimation task with trial-by-trial feedback, participants indicated a target interval (1200 ms) by a motor response. We compared 12 patients tested (in fixed order) under their current levodopa medication ("ON") and after levodopa withdrawal ("OFF") to matched healthy controls (HC), measured twice to control for repetition effects. We assessed time estimation accuracy, trial-to-trial adjustment, as well as task- and feedback-related pupil-linked arousal responses. Patients showed comparable time estimation accuracy ON medication as HC but reduced performance OFF medication. Task-related pupil responses showed the reverse pattern. Trial-to-trial adjustments of response times were reduced in DRD, particularly OFF medication. Our results indicate differential alterations of time estimation accuracy and task-related arousal dynamics in DRD patients as a function of dopaminergic medication state. A medication-independent alteration of task repetition effects in DRD cannot be ruled out with certainty but is discussed as less likely.