bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateral root branching: evolutionary innovations and mechanistic divergence in land plants
Authors: Singh Harshita , Singh Zeenu , Kashyap Rohan , Yadav Shri Ram
Published: March 2023

The root system architecture in plants is a result of multiple evolutionary innovations over time in response to changing environmental cues. Dichotomy and endogenous lateral branching in the roots evolved in lycophytes lineage but extant seed plants use lateral branching instead. This has led to the development of complex and adaptive root systems, with lateral roots playing a key role in this process exhibiting conserved and divergent features in different plant species. The study of lateral root branching in diverse plant species can shed light on the orderly yet distinct nature of postembryonic organogenesis in plants. This insight provides an overview of the diversity in lateral root (LR) development in various plant species during the evolution of root system in plants.
BBX30/miP1b and BBX31/miP1a form a positive feedback loop with ABI5 to regulate ABA‐mediated postgermination seedling growth arrest
Authors: Singh Deeksha , Datta Sourav
Published: March 2023

In plants, the switch to autotrophic growth involves germination followed by postgermination seedling establishment. When environmental conditions are not favorable, the stress hormone abscisic acid (ABA) signals plants to postpone seedling establishment by inducing the expression of the transcription factor ABI5. The levels of ABI5 determine the efficiency of the ABA‐mediated postgermination developmental growth arrest. The molecular mechanisms regulating the stability and activity of ABI5 during the transition to light are less known.

Using genetic, molecular, and biochemical approach, we found that two B‐box domain containing proteins BBX31 and BBX30 alongwith ABI5 inhibit postgermination seedling establishment in a partially interdependent manner.

BBX31 and BBX30 are also characterized as microProteins miP1a and miP1b, respectively, based on their small size, single domain, and ability to interact with multidomain proteins. miP1a/BBX31 and miP1b/BBX30 physically interact with ABI5 to stabilize it and promote its binding to promoters of downstream genes. ABI5 reciprocally induces the expression of BBX30 and BBX31 by directly binding to their promoter.

ABI5 and the two microProteins thereby form a positive feedback loop to promote ABA‐mediated developmental arrest of seedlings.
The role of MIF in periodontitis: A potential pathogenic driver, biomarker, and therapeutic target
Authors: Fang Tongfeng , Liu Liu , Song Dongzhe , Huang Dingming
Published: March 2023

Objective

Periodontitis is an inflammatory disease that involves an imbalance in the oral microbiota, activation of inflammatory and immune responses, and alveolar bone destruction. Macrophage migration inhibitory factor (MIF) is a versatile cytokine involved in several pathological reactions, including inflammatory processes and bone destruction, both of which are characteristics of periodontitis. While the roles of MIF in cancer and other immune diseases have been extensively characterized, its role in periodontitis remains inconclusive.

Results

In this review, we describe a comprehensive analysis of the potential roles of MIF in periodontitis from the perspective of immune response and bone regulation at the cellular and molecular levels. Moreover, we discuss its potential reliability as a novel diagnostic and therapeutic target for periodontitis.

Conclusion

This review can aid dental researchers and clinicians in understanding the current state of MIF‐related pathogenesis, diagnosis, and treatment of periodontitis.
Emergency red cell exchange for the management of acute complications in sickle cell disease: Automated versus manual
Authors: Mihalca Diana , Ahmad Adeel , Mehta Dipal , Freeman Tanya , Orebayo Funmilayo , Bello‐Sanyaolu Oloruntoyin , Lewis Natasha , Chatterjee Basabi , Tsitsikas Dimitris A.
Published: March 2023

Background

Red blood cell exchange is the cornerstone of the management for acute complications of sickle cell disease. It improves anaemia and improvesperipheral tissue oxygen delivery while at the same time reduces the proportion of circulating sickle erythrocytes. Even though automated red cell exchange is very effective in rapidly lowering the Hb S level, 24‐h availability is currently not feasible for most specialist centres including our own.

Objective

Here, we describe our experience using both automated and manual red cell exchange for the management of acute sickle cell complications.

Methods

Eighty‐six such episodes have been recorded between June 2011 and June 2022 comprising of 68 episodes of automated and 18 episodes of manual red cell exchange.

Results

The post procedure Hb S/S + C level was 18% after automated and 36% after manual red cell exchange. The platelet count dropped by 41% and 21% after automated and manual red cell exchange respectively. The clinical outcomes including need for organ support, duration of stay in the intensive care unit and overall length of hospitalisation was comparable between the two groups.

Conclusion

In our experience, manual red cell exchange is a safe and effective alternative to an automated procedure that can be used while specialist centres are building up their capacity to offer automated red cell exchange for all patients requiring the intervention.
Mapping stacks and categorical notions of properness
Authors: Halpern-Leistner Daniel , Preygel Anatoly
Published: March 2023

One fundamental consequence of a scheme $X$ being proper is that the functor classifying maps from $X$ to any other suitably nice scheme or algebraic stack is representable by an algebraic stack. This result has been generalized by replacing $X$ with a proper algebraic stack. We show, however, that it also holds when $X$ is replaced by many examples of algebraic stacks which are not proper, including many global quotient stacks. This leads us to revisit the definition of properness for stacks. We introduce the notion of a formally proper morphism of stacks and study its properties. We develop methods for establishing formal properness in a large class of examples. Along the way, we prove strong $h$-descent results which hold in the setting of derived algebraic geometry but not in classical algebraic geometry. Our main applications are algebraicity results for mapping stacks and the stack of coherent sheaves on a flat and formally proper stack.
The Matrix: connecting and re-using digital records and archives of archaeological investigations
Authors:   Historic England, May Keith , Taylor James S. ,   University of York
Published: March 2023

Stratigraphic data and relationships form the backbone of all the related archaeological records from each excavated site and are essential for integrated analysis, wider synthesis and accessible archiving of the growing body of archaeological data and reports generated through the commercial archaeological sector in the UK and internationally. The stratigraphic record, usually in the form of a stratigraphic matrix, with associated relationships and data, acts as a primary, if not the primary 'evidence' for how, and in what order, the site was excavated. As such the stratigraphic matrix can be the key mechanism that enables anyone less familiar with the site, to re-visit and re-use the excavation records, understand what data is most relevant for addressing certain research questions, or problems encountered, and piece together the underlying details of how the excavator(s) arrived at their interpretations. However such records are often only held on paper or as scanned image copies (as PDFs) of matrix diagrams that cannot easily be re-used with all the associated data. This article presents outcomes from The Matrix project (AHRC AH/T002093/1) that address the current problems caused by the lack of standardized approaches to digital archiving of archaeological data using the case study of stratigraphic and phasing data.
Development of a Novel 4-DOF Flexible Endoscopic Robot Using Cable-Driven Multisegment Continuum Mechanisms
Authors: Wang Zhengyu , Bao Shiyang , Zi Bin , Jia Zirui , Yu Xiang
Published: March 2023

This paper presents the design, analysis, and development of a novel four degrees of freedom (4-DOF) endoscopic robot with cable-driven multisegment flexible continuum mechanisms. The endoscopic robot is mainly composed of the passive positioning arm, cable-pulley system, and 3-DOF flexible continuum mechanism. The forward and inverse kinematics of the endoscopic robot are derived based on the constant curvature assumption, and its working space, flexibility, and preoperative incision determination method are analyzed as well. Based on the hardware structure of the robot system, a control strategy and a control software are developed, and the continuum mechanism is kinematically calibrated to carry out the trajectory planning experiment and simulated surgery experiment. The experimental results show that the calibrated constant curvature model can be used for the motion control of the continuum mechanism, and the 4-DOF endoscopic robot can meet the visual field requirements of minimally invasive surgery.
NiO/β-(AlxGa1−x)2O3/Ga2O3 heterojunction lateral rectifiers with reverse breakdown voltage >7 kV
Authors: Wan Hsiao-Hsuan , Li Jian-Sian , Chiang Chao-Ching , Xia Xinyi , Ren Fan , Masten Hannah N. , Lundh James Spencer , Spencer Joseph A. , Alema Fikadu , Osinsky Andrei , Jacobs Alan G. , Hobart Karl , Tadjer Marko J. , Pearton S. J.
Published: March 2023

NiO/β-(AlxGa1−x)2O3/Ga2O3 heterojunction lateral geometry rectifiers with diameter 50–100 μm exhibited maximum reverse breakdown voltages >7 kV, showing the advantage of increasing the bandgap using the β-(AlxGa1−x)2O3 alloy. This Si-doped alloy layer was grown by metal organic chemical vapor deposition with an Al composition of ∼21%. On-state resistances were in the range of 50–2180 Ω cm2, leading to power figures-of-merit up to 0.72 MW cm−2. The forward turn-on voltage was in the range of 2.3–2.5 V, with maximum on/off ratios >700 when switching from 5 V forward to reverse biases up to −100 V. Transmission line measurements showed the specific contact resistance was 0.12 Ω cm2. The breakdown voltage is among the highest reported for any lateral geometry Ga2O3-based rectifier.
Chemokines expressed by engineered bacteria recruit and orchestrate antitumor immunity
Authors: Savage Thomas M. , Vincent Rosa L. , Rae Sarah S. , Huang Lei Haley , Ahn Alexander , Pu Kelly , Li Fangda , de los Santos-Alexis Kenia , Coker Courtney , Danino Tal , Arpaia Nicholas
Published: March 2023

Tumors use multiple mechanisms to actively exclude immune cells involved in antitumor immunity. Strategies to overcome these exclusion signals remain limited due to an inability to target therapeutics specifically to the tumor. Synthetic biology enables engineering of cells and microbes for tumor-localized delivery of therapeutic candidates previously unavailable using conventional systemic administration techniques. Here, we engineer bacteria to intratumorally release chemokines to attract adaptive immune cells into the tumor environment. Bacteria expressing an activating mutant of the human chemokine CXCL16 (hCXCL16
K42A
) offer therapeutic benefit in multiple mouse tumor models, an effect mediated via recruitment of CD8
+
T cells. Furthermore, we target the presentation of tumor-derived antigens by dendritic cells, using a second engineered bacterial strain expressing CCL20. This led to type 1 conventional dendritic cell recruitment and synergized with hCXCL16
K42A
-induced T cell recruitment to provide additional therapeutic benefit. In summary, we engineer bacteria to recruit and activate innate and adaptive antitumor immune responses, offering a new cancer immunotherapy strategy.
Ferroptosis MRI for early detection of anticancer drug–induced acute cardiac/kidney injuries
Authors: Zeng Fantian , Nijiati Sureya , Liu Yangtengyu , Yang Qinqin , Liu Xiaomin , Zhang Qianyu , Chen Shi , Su Anqi , Xiong Hehe , Shi Changrong , Cai Congbo , Lin Zhongning , Chen Xiaoyuan , Zhou Zijian
Published: March 2023

Ferroptosis has been realized in anticancer drug–induced acute cardiac/kidney injuries (ACI/AKI); however, molecular imaging approach to detect ferroptosis in ACI/AKI is a challenge. We report an artemisinin-based probe (Art-Gd) for contrast-enhanced magnetic resonance imaging of ferroptosis (feMRI) by exploiting the redox-active Fe(II) as a vivid chemical target. In vivo, the Art-Gd probe showed great feasibility in early diagnosis of anticancer drug–induced ACI/AKI, which was at least 24 and 48 hours earlier than the standard clinical assays for assessing ACI and AKI, respectively. Furthermore, the feMRI was able to provide imaging evidence for the different mechanisms of action of ferroptosis-targeted agents, either by blocking lipid peroxidation or depleting iron ions. This study presents a feMRI strategy with simple chemistry and robust efficacy for early evaluation of anticancer drug–induced ACI/AKI, which may shed light on the theranostics of a variety of ferroptosis-related diseases.
Knots are not for naught: Design, properties, and topology of hierarchical intertwined microarchitected materials
Authors: Moestopo Widianto P. , Shaker Sammy , Deng Weiting , Greer Julia R.
Published: March 2023

Lightweight and tough engineered materials are often designed with three-dimensional hierarchy and interconnected structural members whose junctions are detrimental to their performance because they serve as stress concentrations for damage accumulation and lower mechanical resilience. We introduce a previously unexplored class of architected materials, whose components are interwoven and contain no junctions, and incorporate micro-knots as building blocks within these hierarchical networks. Tensile experiments, which show close quantitative agreements with an analytical model for overhand knots, reveal that knot topology allows a new regime of deformation capable of shape retention, leading to a ~92% increase in absorbed energy and an up to ~107% increase in failure strain compared to woven structures, along with an up to ~11% increase in specific energy density compared to topologically similar monolithic lattices. Our exploration unlocks knotting and frictional contact to create highly extensible low-density materials with tunable shape reconfiguration and energy absorption capabilities.
The TORC1 activates Rpd3L complex to deacetylate Ino80 and H2A.Z and repress autophagy
Authors: Li Xin , Mei Qianyun , Yu Qi , Wang Min , He Fei , Xiao Duncheng , Liu Huan , Ge Feng , Yu Xilan , Li Shanshan
Published: March 2023

Autophagy is a critical process to maintain homeostasis, differentiation, and development. How autophagy is tightly regulated by nutritional changes is poorly understood. Here, we identify chromatin remodeling protein Ino80 and histone variant H2A.Z as the deacetylation targets for histone deacetylase Rpd3L complex and uncover how they regulate autophagy in response to nutrient availability. Mechanistically, Rpd3L deacetylates Ino80 K929, which protects Ino80 from being degraded by autophagy. The stabilized Ino80 promotes H2A.Z eviction from autophagy-related genes, leading to their transcriptional repression. Meanwhile, Rpd3L deacetylates H2A.Z, which further blocks its deposition into chromatin to repress the transcription of autophagy-related genes. Rpd3-mediated deacetylation of Ino80 K929 and H2A.Z is enhanced by the target of rapamycin complex 1 (TORC1). Inactivation of TORC1 by nitrogen starvation or rapamycin inhibits Rpd3L, leading to induction of autophagy. Our work provides a mechanism for chromatin remodelers and histone variants in modulating autophagy in response to nutrient availability.
Ultrasound-triggered interfacial engineering-based microneedle for bacterial infection acne treatment
Authors: Xiang Yiming , Lu Jiali , Mao Congyang , Zhu Yizhou , Wang Chaofeng , Wu Jun , Liu Xiangmei , Wu Shuilin , Kwan Kenny Y. H. , Cheung Kenneth M. C. , Yeung Kelvin W. K.
Published: March 2023

Acne is an inflammatory skin disease mainly caused by
Propionibacterium acnes
, which can cause local inflammatory reactions and develop into chronic inflammatory diseases in severe cases. To avoid the use of antibiotics and to effectively treat the site of acne, we report a sodium hyaluronate microneedle patch that mediates the transdermal delivery of ultrasound-responsive nanoparticles for the effective treatment of acne. The patch contains nanoparticles formed by zinc porphyrin–based metal-organic framework and zinc oxide (ZnTCPP@ZnO). We demonstrated activated oxygen-mediated killing of
P. acnes
with an antibacterial efficiency of 99.73% under 15 min of ultrasound irradiation, resulting in a decrease in levels of acne-related factors, including tumor necrosis factor–α, interleukins, and matrix metalloproteinases. The zinc ions up-regulated DNA replication–related genes, promoting the proliferation of fibroblasts and, consequently, skin repair. This research leads to a highly effective strategy for acne treatment through the interface engineering of ultrasound response.
Direct air capture (DAC) and sequestration of CO
2
: Dramatic effect of coordinated Cu(II) onto a chelating weak base ion exchanger
Authors: Chen Hao , Dong Hang , Shi Zhongyu , SenGupta Arup K.
Published: March 2023

Direct air capture (DAC) is important for achieving net-zero greenhouse gas emissions by 2050. However, the ultradilute atmospheric CO
2
concentration (~400 parts per million) poses a formidable hurdle for high CO
2
capture capacities using sorption-desorption processes. Here, we present a Lewis acid-base interaction–derived hybrid sorbent with polyamine-Cu(II) complex enabling over 5.0 mol of CO
2
capture/kg sorbent, nearly two to three times greater capacity than most of the DAC sorbents reported to date. The hybrid sorbent, such as other amine-based sorbents, is amenable to thermal desorption at less than 90°C. In addition, seawater was validated as a viable regenerant, and the desorbed CO
2
is simultaneously sequestered as innocuous, chemically stable alkalinity (NaHCO
3
). The dual-mode regeneration offers unique flexibility and facilitates using oceans as decarbonizing sinks to widen DAC application opportunities.
Simultaneous control of infection and inflammation with keratin-derived antibacterial peptides targeting TLRs and co-receptors
Authors: Sun Yan , Chan Jonathan , Bose Karthikeyan , Tam Connie
Published: March 2023

Controlling infection-driven inflammation is a major clinical dilemma because of limited therapeutic options and possible adverse effects on microbial clearance. Compounding this difficulty is the continued emergence of drug-resistant bacteria, where experimental strategies aiming to augment inflammatory responses for enhanced microbial killing are not applicable treatment options for infections of vulnerable organs. As with corneal infections, severe or prolonged inflammation jeopardizes corneal transparency, leading to devastating vision loss. We hypothesized that keratin 6a–derived antimicrobial peptides (KAMPs) may be a two-pronged remedy capable of tackling bacterial infection and inflammation at once. We used murine peritoneal neutrophils and macrophages, together with an in vivo model of sterile corneal inflammation, to find that nontoxic and prohealing KAMPs with natural 10– and 18–amino acid sequences suppressed lipoteichoic acid (LTA)– and lipopolysaccharide (LPS)–induced NFκB and IRF3 activation, proinflammatory cytokine production, and phagocyte recruitment independently of their bactericidal function. Mechanistically, KAMPs not only competed with bacterial ligands for cell surface Toll-like receptor (TLR) and co-receptors (MD2, CD14, and TLR2) but also reduced cell surface availability of TLR2 and TLR4 through promotion of receptor endocytosis. Topical KAMP treatment effectively alleviated experimental bacterial keratitis, as evidenced by substantial reductions of corneal opacification, inflammatory cell infiltration, and bacterial burden. These findings reveal the TLR-targeting activities of KAMPs and demonstrate their therapeutic potential as a multifunctional drug for managing infectious inflammatory disease.
Review of Clinical and Laboratory Diagnostics for Coccidioidomycosis
Authors: McHardy Ian H. , Barker Bridget , Thompson George R.
Published: March 2023

Coccidioidomycosis is a fungal disease associated with soil exposure that frequently goes undiagnosed due at least in part to its nonspecific presentation and the lack of clinical suspicion by health care providers. Currently available diagnostics for coccidioidomycosis offer qualitative results that can suffer from low specificity, while semiquantitative assays are labor-intensive and complex and can require multiple days to complete.
Functional Dichotomy for a Hyphal Repressor in Candida albicans
Authors: Mao Yinhe , Solis Norma V. , Filler Scott G. , Mitchell Aaron P.
Published: March 2023

Hypha formation is a central virulence trait of the fungal pathogen
Candida albicans
. Control of hypha formation has been studied in detail in the type strain but not in other diverse
C. albicans
clinical isolates.
Primary angiosarcoma of the breast in an early adolescent female
Authors: Lee Chanyang , Falkner Nathalie , Kamyab Roshanak , Li Ran
Published: March 2023

Primary angiosarcoma of the breast is a rare and aggressive malignancy, which arises from endothelial cells lining blood vessels. It represents less than 0.05% of all breast cancers, and more commonly affects relatively younger individuals. Reaching the correct diagnosis may be delayed, because imaging is not typical of other breast malignancies and can mimic benign processes. Clinical presentation is variable, ranging from diffuse breast oedema to a palpable discrete mass. An early adolescent female presented to her general practitioner with a palpable breast lump on self-examination. The diagnosis of primary breast angiosarcoma was confirmed on biopsy. She underwent a complete surgical resection and adjuvant chemotherapy. She remains in remission after 3 years and is undergoing regular surveillance. Due to the rarity of this condition, there is no established clinical management protocol for this condition currently. Early detection, aggressive treatment and ongoing surveillance provide the best chance of prolonged disease-free survival.
Feingold syndrome type 1: a rare cause of fetal microcephaly (prenatal diagnosis)
Authors: Gouveia Inês , Geraldo Ana Filipa , Godinho Cristina , Castedo Sérgio
Published: March 2023

We report a case of fetal microcephaly found during the second trimester ultrasound and confirmed by further ultrasound scans and fetal MRI. The array comparative genomic hybridisation analysis of the fetus and the male parent showed a 1.5 Mb deletion overlapping the Feingold syndrome region, an autosomal dominant syndrome that can cause microcephaly, facial/hand abnormalities, mild neurodevelopmental delay and others. This case illustrates the need for a detailed investigation by a multidisciplinary team to provide prenatal counselling regarding a postnatal outcome to the parents and orient their decision towards the continuation or termination of pregnancy.
Internal consistency reliability of mental health questionnaires in college student athletes
Authors: Taylor Daniel J , Huskey Alisa , Kim Kelly N , Emert Sarah E , Wardle-Pinkston Sophie , Auerbach Alex , Ruiz John M , Grandner Michael A , Webb Rachel , Skog Michelle , Milord Thomas
Published: March 2023

Objectives

To examine the internal consistency reliability and measurement invariance of a questionnaire battery designed to identify college student athletes at risk for mental health symptoms and disorders.

Methods

College student athletes (N=993) completed questionnaires assessing 13 mental health domains: strain, anxiety, depression, suicide and self-harm ideation, sleep, alcohol use, drug use, eating disorders, attention deficit hyperactivity disorder (ADHD), bipolar disorder, post-traumatic stress disorder (PTSD), gambling and psychosis. Internal consistency reliability of each measure was assessed and compared between sexes as well as to previous results in elite athletes. Discriminative ability analyses were used to examine how well the cut-off score on the strain measure (Athlete Psychological Strain Questionnaire) predicted cut-offs on other screening questionnaires.

Results

Strain, anxiety, depression, suicide and self-harm ideation, ADHD, PTSD and bipolar questionnaires all had acceptable or better internal consistency reliability. Sleep, gambling and psychosis questionnaires had questionable internal consistency reliability, although approaching acceptable for certain sex by measure values. The athlete disordered eating measure (Brief Eating Disorder in Athletes Questionnaire) had poor internal consistency reliability in males and questionable internal consistency reliability in females.

Conclusions

The recommended mental health questionnaires were generally reliable for use with college student athletes. To truly determine the validity of the cut-off scores on these self-report questionnaires, future studies need to compare the questionnaires to a structured clinical interview to determine the discriminative abilities.
Let’s talk about sex (and gender) after ACL injury: a systematic review and meta-analysis of self-reported activity and knee-related outcomes
Authors: Bruder Andrea M , Culvenor Adam G , King Matthew G , Haberfield Melissa , Roughead Eliza A , Mastwyk John , Kemp Joanne L , Ferraz Pazzinatto Marcella , West Thomas J , Coburn Sally L , Cowan Sallie M , Ezzat Allison M , To Laura , Chilman Karina , Couch Jamon L , Whittaker Jackie L , Crossley Kay M
Published: March 2023

Objective

Investigate sex/gender differences in self-reported activity and knee-related outcomes after anterior cruciate ligament (ACL) injury.

Design

Systematic review with meta-analysis.

Data sources

Seven databases were searched in December 2021.

Eligibility criteria

Observational or interventional studies with self-reported activity (including return to sport) or knee-related outcomes after ACL injury.

Results

We included 242 studies (n=123 687, 43% females/women/girls, mean age 26 years at surgery). One hundred and six studies contributed to 1 of 35 meta-analyses (n=59 552). After ACL injury/reconstruction, very low-certainty evidence suggests females/women/girls had inferior self-reported activity (ie, return to sport, Tegner Activity Score, Marx Activity Scale) compared with males/men/boys on most (88%, 7/8) meta-analyses. Females/women/girls had 23%–25% reduced odds of returning to sport within 1-year post-ACL injury/reconstruction (12 studies, OR 0.76 95% CI 0.63 to 0.92), 1–5 years (45 studies, OR 0.75 95% CI 0.69 to 0.82) and 5–10 years (9 studies, OR 0.77 95% CI 0.57 to 1.04). Age-stratified analysis (<19 years) suggests female athletes/girls had 32% reduced odds of returning to sport compared with male athletes/boys (OR 0.68, 95% CI 0.41 to 1.13, I20.0%). Very low-certainty evidence suggests females/women/girls experienced inferior knee-related outcomes (eg, function, quality of life) on many (70%, 19/27) meta-analyses: standardised mean difference ranging from −0.02 (Knee injury and Osteoarthritis Outcome Score, KOOS-activities of daily living, 9 studies, 95% CI −0.05 to 0.02) to −0.31 (KOOS-sport and recreation, 7 studies, 95% CI −0.36 to –0.26).

Conclusions

Very low-certainty evidence suggests inferior self-reported activity and knee-related outcomes for females/women/girls compared with males/men/boys after an ACL injury. Future studies should explore factors and design targeted interventions to improve outcomes for females/women/girls.

PROSPERO registration number

CRD42021205998.
Mediation of an association between neighborhood socioeconomic environment and type 2 diabetes through the leisure-time physical activity environment in an analysis of three independent samples
Authors: Moon Katherine A , Nordberg Cara M , Orstad Stephanie L , Zhu Aowen , Uddin Jalal , Lopez Priscilla , Schwartz Mark D , Ryan Victoria , Hirsch Annemarie G , Schwartz Brian S , Carson April P , Long D Leann , Meeker Melissa , Brown Janene , Lovasi Gina S , Adhikari Samranchana , Kanchi Rania , Avramovic Sanja , Imperatore Giuseppina , Poulsen Melissa N
Published: March 2023

Introduction

Inequitable access to leisure-time physical activity (LTPA) resources may explain geographic disparities in type 2 diabetes (T2D). We evaluated whether the neighborhood socioeconomic environment (NSEE) affects T2D through the LTPA environment.

Research design and methods

We conducted analyses in three study samples: the national Veterans Administration Diabetes Risk (VADR) cohort comprising electronic health records (EHR) of 4.1 million T2D-free veterans, the national prospective cohort REasons for Geographic and Racial Differences in Stroke (REGARDS) (11 208 T2D free), and a case–control study of Geisinger EHR in Pennsylvania (15 888 T2D cases). New-onset T2D was defined using diagnoses, laboratory and medication data. We harmonized neighborhood-level variables, including exposure, confounders, and effect modifiers. We measured NSEE with a summary index of six census tract indicators. The LTPA environment was measured by physical activity (PA) facility (gyms and other commercial facilities) density within street network buffers and population-weighted distance to parks. We estimated natural direct and indirect effects for each mediator stratified by community type.

Results

The magnitudes of the indirect effects were generally small, and the direction of the indirect effects differed by community type and study sample. The most consistent findings were for mediation via PA facility density in rural communities, where we observed positive indirect effects (differences in T2D incidence rates (95% CI) comparing the highest versus lowest quartiles of NSEE, multiplied by 100) of 1.53 (0.25, 3.05) in REGARDS and 0.0066 (0.0038, 0.0099) in VADR. No mediation was evident in Geisinger.

Conclusions

PA facility density and distance to parks did not substantially mediate the relation between NSEE and T2D. Our heterogeneous results suggest that approaches to reduce T2D through changes to the LTPA environment require local tailoring.
Proposed triggers for retiring a living systematic review
Authors: Murad Mohammad Hassan , Wang Zhen , Chu Haitao , Lin Lifeng , El Mikati Ibrahim K , Khabsa Joanne , Akl Elie A , Nieuwlaat Robby , Schuenemann Holger J , Riaz Irbaz Bin
Published: March 2023

Living systematic reviews (LSRs) are systematic reviews that are continually updated, incorporating relevant new evidence as it becomes available. LSRs are critical for decision-making in topics where the evidence continues to evolve. It is not feasible to continue to update LSRs indefinitely; however, guidance on when to retire LSRs from the living mode is not clear. We propose triggers for making such a decision. The first trigger is to retire LSRs when the evidence becomes conclusive for the outcomes that are required for decision-making. Conclusiveness of evidence is best determined based on the GRADE certainty of evidence construct, which is more comprehensive than solely relying on statistical considerations. The second trigger to retire LSRs is when the question becomes less pertinent for decision-making as determined by relevant stakeholders, including people affected by the problem, healthcare professionals, policymakers and researchers. LSRs can also be retired from a living mode when new studies are not anticipated to be published on the topic and when resources become unavailable to continue updating. We describe examples of retired LSRs and apply the proposed approach using one LSR about adjuvant tyrosine kinase inhibitors in high-risk renal cell carcinoma that we retired from a living mode and published its last update.
Examining non-linearity in the association between age and reported opioid use in different socioeconomic strata: cohort study using Health Survey for England waves from 1997 to 2014
Authors: Nowakowska Magdalena , Zghebi Salwa S , Chen Li-Chia , Ashcroft Darren M , Kontopantelis Evangelos
Published: March 2023

Background

Age and socioeconomic status (SES) predict several health-related outcomes, including prescription opioid use. Contrasting findings from previous literature found higher prevalence of opioid use in both people over 65 years old and the working-age population of 35–55 years old. This study aimed to analyse if the association between age and opioid use is non-linear and differs in adults with different SES levels.

Methods

This cohort study used the Health Survey for England waves 1997–2014 data to investigate the shape of the correlation between reported opioid use and income decile, employment status and educational level. A semiparametric Generalised Additive Model was employed, so that linearity of correlation was not assumed. The shape of the relationship was assessed using the effective degrees of freedom (EDF).

Results

Positive correlation between age and reported opioid use, more linear in people in the highest income decile (EDF: 1.01, p<0.001) and higher education (EDF: 2.03, p<0.001) was observed. In people on lower income and with lower levels of education, the highes probability of reported opioid use was at around 40–60 years old and slowly decreased after that. Higher income decile and higher levels of education were predictors of a lower probability of reported opioid use (OR: 0.27, 95% CI: 0.21 to 0.36 and OR: 0.48, 95% CI: 0.41 to 0.57, respectively). There was no statistically significant difference in opioid use between employed and unemployed people.

Conclusion

The relationship between age and the probability of prescribed opioid use varies greatly across different income and educations strata, highlighting different drivers in opioid prescribing across population groups. More research is needed into exploring patterns in opioid use in older people, particularly from disadvantaged socioeconomic backgrounds.
Education mediating the associations between early life factors and frailty: a cross-sectional study of the UK Biobank
Authors: Maharani Asri , Didikoglu Altug , O'Neill Terence W , Pendleton Neil , Canal Maria Mercè , Payton Antony
Published: March 2023

Objectives

Exposures in utero and during infancy may impact the development of diseases later in life. They may be linked with development of frailty, although the mechanism is unclear. This study aims to determine the associations between early life risk factors and development of frailty among middle-aged and older adults as well as potential pathways via education, for any observed association.

Design

A cross-sectional study.

Settings

This study used data from UK Biobank, a large population-based cohort.

Participants

502 489 individuals aged 37–73 years were included in the analysis.

Primary and secondary outcome measures

Early life factors in this study included being breast fed as a baby, maternal smoking, birth weight, the presence of perinatal diseases, birth month and birth place (in or outside the UK). We developed a frailty index comprising 49 deficits. We used generalised structural equation modelling to examine the associations between early life factors and development of frailty and whether any observed association was mediated via educational attainment.

Results

A history of breast feeding and normal birth weight were associated with a lower frailty index while maternal smoking, the occurrence of perinatal diseases and birth month with a longer day length were associated with a higher frailty index. Educational level mediated the relationship between these early life factors and frailty index.

Conclusions

This study highlights that biological and social risk occurring at different stages of life are related to the variations in frailty index in later life and suggests opportunities for prevention across the life course.
Diagnostic value of PET with different radiotracers and MRI for recurrent glioma: a Bayesian network meta-analysis
Authors: Xiaoxue Tian , Yinzhong Wang , Meng Qi , Lu Xingru , Lei Junqiang
Published: March 2023

Objective

The purpose of this study was to evaluate the diagnostic accuracy of 6 different imaging modalities for differentiating glioma recurrence from postradiotherapy changes by performing a network meta-analysis (NMA) using direct comparison studies with 2 or more imaging techniques.

Data sources

PubMed, Scopus, EMBASE, the Web of Science and the Cochrane Library were searched from inception to August 2021. The Confidence In Network Meta-Analysis (CINeMA) tool was used to evaluate the quality of the included studies with the criterion for study inclusion being direct comparison using 2 or more imaging modalities.

Data extraction and synthesis

The consistency was evaluated by examining the agreement between direct and indirect effects. NMA was performed and the surface under the the cumulative ranking curve (SUCRA) values was obtained to calculate the probability of each imaging modality being the most effective diagnostic method. The CINeMA tool was used to evaluate the quality of the included studies.

Main outcomes and measures

Direct comparison, inconsistency test, NMA and SUCRA values.

Results

A total of 8853 potentially relevant articles were retrieved and 15 articles met the inclusion criteria.18F-FET showed the highest SUCRA values for sensitivity, specificity, positive predictive value and accuracy, followed by18F-FDOPA. The quality of the included evidence is classified as moderate.

Conclusion and relevance

This review indicates that18F-FET and18F-FDOPA may have greater diagnostic value for glioma recurrence relative to other imaging modalities (Grading of Recommendations, Assessment, Development and Evaluations B).

PROSPERO registration number

CRD42021293075.
Association between burnout and adherence with mask usage and additional COVID-19 prevention behaviours: findings from a large-scale, demographically representative survey of US adults
Authors: Czeisler Mark É , Wolkow Alexander P , Czeisler Charles A , Howard Mark E , Rajaratnam Shantha M W , Lane Rashon I
Published: March 2023

Objectives

Studies have found associations between occupational burnout symptoms and reduced engagement with healthy behaviours. We sought to characterise demographic, employment and sleep characteristics associated with occupational burnout symptoms, and to evaluate their relationships with adherence to COVID-19 prevention behaviours (mask usage, hand hygiene, avoiding gatherings, physical distancing, obtaining COVID-19 tests if potentially infected).

Methods

During December 2020, surveys were administered cross-sectionally to 5208 US adults (response rate=65.8%). Quota sampling and survey weighting were employed to improve sample representativeness of sex, age and race and ethnicity. Among 3026 employed respondents, logistic regression models examined associations between burnout symptoms and demographic, employment and sleep characteristics. Similar models were conducted to estimate associations between burnout and non-adherence with COVID-19 prevention behaviours.

Results

Women, younger adults, unpaid caregivers, those working more on-site versus remotely and those with insufficient or impaired sleep had higher odds of occupational burnout symptoms. Burnout symptoms were associated with less frequent mask usage (adjusted odds ratio (aOR)=1.7, 95% CI 1.3–2.1), hand hygiene (aOR=2.1, 95% CI 1.7–2.7), physical distancing (aOR=1.3, 95% CI 1.1–1.6), avoiding gatherings (aOR=1.4, 95% CI 1.1–1.7) and obtaining COVID-19 tests (aOR=1.4, 95% CI 1.1–1.8).

Conclusions

Disparities in occupational burnout symptoms exist by gender, age, caregiving, employment and sleep health. Employees experiencing occupational burnout symptoms might exhibit reduced adherence with COVID-19 prevention behaviours. Employers can support employee health by addressing the psychological syndrome of occupational burnout.
Quality contract ‘prevention of postoperative delirium in the care of elderly patients’ study protocol: a non-randomised, pre–post, monocentric, prospective trial
Authors: Yürek Fatima , Zimmermann Julian-Dominic , Weidner Elisa , Hauß Armin , Dähnert Enrico , Hadzidiakos Daniel , Kruppa Jochen , Kiselev Joern , Sichinava Natia , Retana Romero Oscar Andrés , Hoff Laerson , Mörgeli Rudolf , Junge Lennart , Scholtz Kathrin , Piper Sophie K , Grüner Luzie , Harborth Antonia Eva Maria , Eymold Lisa , Gülmez Tuba , Falk Elke , Balzer Felix , Treskatsch Sascha , Höft Moritz , Schmidt Dieter , Landgraf Franziska , Marschall Ursula , Hölscher Andreas , Rafii Mani , Spies Claudia
Published: March 2023

Introduction

Postoperative delirium (POD) is seen in approximately 15% of elderly patients and is related to poorer outcomes. In 2017, the Federal Joint Committee (Gemeinsamer Bundesausschuss) introduced a ‘quality contract’ (QC) as a new instrument to improve healthcare in Germany. One of the four areas for improvement of in-patient care is the ‘Prevention of POD in the care of elderly patients’ (QC-POD), as a means to reduce the risk of developing POD and its complications.

The Institute for Quality Assurance and Transparency in Health Care identified gaps in the in-patient care of elderly patients related to the prevention, screening and treatment of POD, as required by consensus-based and evidence-based delirium guidelines. This paper introduces the QC-POD protocol, which aims to implement these guidelines into the clinical routine. There is an urgent need for well-structured, standardised and interdisciplinary pathways that enable the reliable screening and treatment of POD. Along with effective preventive measures, these concepts have a considerable potential to improve the care of elderly patients.

Methods and analysis

The QC-POD study is a non-randomised, pre–post, monocentric, prospective trial with an interventional concept following a baseline control period. The QC-POD trial was initiated on 1 April 2020 between Charité-Universitätsmedizin Berlin and the German health insurance company BARMER and will end on 30 June 2023. Inclusion criteria: patients 70 years of age or older that are scheduled for a surgical procedure requiring anaesthesia and insurance with the QC partner (BARMER). Exclusion criteria included patients with a language barrier, moribund patients and those unwilling or unable to provide informed consent. The QC-POD protocol provides perioperative intervention at least two times per day, with delirium screening and non-pharmacological preventive measures.

Ethics and dissemination

This protocol was approved by the ethics committee of the Charité-Universitätsmedizin, Berlin, Germany (EA1/054/20). The results will be published in a peer-reviewed scientific journal and presented at national and international conferences.

Trial registration number

NCT04355195.
Heatwaves, hospitals and health system resilience in England: a qualitative assessment of frontline perspectives from the hot summer of 2019
Authors: Brooks Katya , Landeg Owen , Kovats Sari , Sewell Mark , OConnell Emer
Published: March 2023

Objective

To critically assess the impacts of very hot weather on (i) frontline staff in hospitals in England and (ii) on healthcare delivery and patient safety.

Study design

A qualitative study design using key informant semi-structured interviews, preinterview survey and thematic analysis.

Setting

England.

Participants

14 health professionals in the National Health Service (clinicians and non-clinicians, including facilities managers and emergency preparedness, resilience and response professionals).

Results

Hot weather in 2019 caused significant disruption to health services, facilities and equipment, staff and patient discomfort, and an acute increase in hospital admissions. Levels of awareness varied between clinical and non-clinical staff of the Heatwave Plan for England, Heat-Health Alerts and associated guidance. Response to heatwaves was affected by competing priorities and tensions including infection control, electric fan usage and patient safety.

Conclusions

Healthcare delivery staff experience difficulty in managing heat risks in hospitals. Priority should be given to workforce development and strategic, long-term planning, prevention and investment to enable staff to prepare and respond, as well as to improve health system resilience to current and future heat-health risks. Further research with a wider, larger cohort is required to develop the evidence base on the impacts, including the costs of those impacts, and to assess the effectiveness and feasibility of interventions. Forming a national picture of health system resilience to heatwaves will support national adaptation planning for health, in addition to informing strategic prevention and effective emergency response.
Association between seropositivity for toxocariasis and cognitive functioning in older adults: an analysis of cross-sectional data from the US National Health and Nutrition Examination Survey (NHANES), 2011–2014
Authors: Song Ge , Yang Chao , Qu Zhe , Lin Xuechun , Liu Minhui , Wang Yanhong
Published: March 2023

Objectives

This study sought to examine the relationship between seropositivity for toxocariasis and cognitive functioning in a nationally representative sample of US older adults.

Design

A cross-sectional study.

Setting

National Health and Nutrition Examination Survey (NHANES) data collection took place in the US at participants’ homes and mobile examination centres with specialised equipment.

Participants

The study population consisted of 3188 community-dwelling US older adults aged 60 and above from the NHANES 2011 to 2014.

Outcome measures

IgG antibody againstToxocaraspp was tested by a Luminex assay using recombinant rTc-CTL-1 antigen. A value >23.1 mean fluorescence intensity (MFI) indicated positive for toxocariasis and a value ≤23.1 MFI as negative for toxocariasis. The Consortium to Establish a Registry for Alzheimer’s Disease Word Learning subtest immediate and delayed memory, the Animal Fluency test and the Digit Symbol Substitution Test (DSST) were used to assess cognitive functioning. Cognitive test-specific and global cognitive z scores were computed using sample means and SD.

Results

The study population consisted of 3188 participants who represented a total of 111 896 309 civilian citizens in the USA. The mean age of the participants was 69.6 years (standard deviation 6.8). The prevalence of toxocariasis in this population was 7.3% (95% confidence interval [CI] 6.1% to 8.5%). The survey-weighted linear regression model showed that compared with participants who were toxocariasis seronegative, those who were seropositive had lower DSST z score (beta [β] = −0.12, 95% CI −0.22 to −0.01) and global cognition z score (β=−0.11, 95% CI −0.22 to −0.01), after controlling for age, sex, race/ethnicity, education, depressive symptoms, smoking status, body mass index, prevalent coronary heart disease, prevalent stroke, and systolic blood pressure, physical activity, and total cholesterol.

Conclusions

In our study, seropositive toxocariasis was independently and significantly associated with worse working memory, sustained attention, processing speed and global cognition in older adults. If this association is causal, public health measures to prevent human toxocariasis might help protect older adults’ cognitive function.