bluuebunny/crossref_metadata_2025 huggingface dataset:
The Inner Loop of Collective Human–Machine Intelligence
Authors: Yang Scott Cheng‐Hsin , Folke Tomas , Shafto Patrick
Published: February 2023

With the rise of artificial intelligence (AI) and the desire to ensure that such machines work well with humans, it is essential for AI systems to actively model their human teammates, a capability referred to as Machine Theory of Mind (MToM). In this paper, we introduce the inner loop of human–machine teaming expressed as communication with MToM capability. We present three different approaches to MToM: (1) constructing models of human inference with well‐validated psychological theories and empirical measurements; (2) modeling human as a copy of the AI; and (3) incorporating well‐documented domain knowledge about human behavior into the above two approaches. We offer a formal language for machine communication and MToM, where each term has a clear mechanistic interpretation. We exemplify the overarching formalism and the specific approaches in two concrete example scenarios. Related work that demonstrates these approaches is highlighted along the way. The formalism, examples, and empirical support provide a holistic picture of the inner loop of human–machine teaming as a foundational building block of collective human–machine intelligence.
The mutual regulation between DcEBF1/2 and DcEIL3‐1 is involved in ethylene induced petal senescence in carnation (Dianthus caryophyllus L.)
Authors: Zhu Chunlin , Huang Zhiheng , Sun Zheng , Feng Shan , Wang Siqi , Wang Teng , Yuan Xinyi , Zhong Linlin , Cheng Yunjiang , Bao Manzhu , Zhang Fan
Published: February 2023

Carnation (Dianthus caryophyllus L.) is a respiratory climacteric flower, comprising one of the most important cut flowers that is extremely sensitive to plant hormone ethylene. Ethylene signaling core transcription factor DcEIL3‐1 plays a key role in ethylene induced petal senescence in carnation. However, how the dose of DcEIL3‐1 is regulated in the carnation petal senescence process is still not clear. Here, we screened out two EBF (EIN3 Binding F‐box) genes, DcEBF1 and DcEBF2, which showed quick elevation by ethylene treatment according to the ethylene induced carnation petal senescence transcriptome. Silencing of DcEBF1 and DcEBF2 accelerated, whereas overexpression of DcEBF1 and DcEBF2 delayed, ethylene induced petal senescence in carnation by influencing DcEIL3‐1 downstream target genes but not DcEIL3‐1 itself. Furthermore, DcEBF1 and DcEBF2 interact with DcEIL3‐1 to degrade DcEIL3‐1 via an ubiquitination pathway in vitro and in vivo. Finally, DcEIL3‐1 binds to the promoter regions of DcEBF1 and DcEBF2 to activate their expression. In conclusion, the present study reveals the mutual regulation between DcEBF1/2 and DcEIL3‐1 during ethylene induced petal senescence in carnation, which not only expands our understanding about ethylene signal regulation network in the carnation petal senescence process, but also provides potential targets with respect to breeding a cultivar of long‐lived cut carnation.
Peripheral sensory function in non‐freezing cold injury patients and matched controls
Authors: Wright Jennifer , Massey Heather , Hollis Sarah , Vale Tom , Bennett David LH. , Maley Matthew , Montgomery Hugh , Tipton Michael , Eglin Clare
Published: February 2023

The aim of this study was to compare peripheral sensory neural function of individuals with non‐freezing cold injury (NFCI) with matched controls (without NFCI) with either similar (COLD) or minimal previous cold exposure (CON). Thirteen individuals with chronic NFCI in their feet were matched with the control groups for sex, age, race, fitness, body mass index and foot volume. All undertook quantitative sensory testing (QST) on the foot. Intraepidermal nerve fibre density (IENFD) was assessed 10 cm above the lateral malleolus in nine NFCI and 12 COLD participants. Warm detection threshold was higher at the great toe in NFCI than COLD (NFCI 45.93 (4.71)°C vs. COLD 43.44 (2.72)°C, P = 0.046), but was non‐significantly different from CON (CON 43.92 (5.01)°C, P = 0.295). Mechanical detection threshold on the dorsum of the foot was higher in NFCI (23.61 (33.59) mN) than in CON (3.83 (3.69) mN, P = 0.003), but was non‐significantly different from COLD (10.49 (5.76) mN, P > 0.999). Remaining QST measures did not differ significantly between groups. IENFD was lower in NFCI than COLD (NFCI 8.47 (2.36) fibre/mm2 vs. COLD 11.93 (4.04) fibre/mm2, P = 0.020). Elevated warm and mechanical detection thresholds may indicate hyposensitivity to sensory stimuli in the injured foot for individuals with NFCI and may be due to reduced innervation given the reduction in IENFD. Longitudinal studies are required to identify the progression of sensory neuropathy from the formation of injury to its resolution, with appropriate control groups employed.
“WOT” Do We Know and Do About Physical Activity of Children and Adolescents With Disabilities? A SWOT-Oriented Synthesis of Para Report Cards
Authors: Hutzler Yeshayahu , Barak Sharon , Aubert Salomé , Arbour-Nicitopoulos Kelly , Tesler Riki , Sit Cindy , Silva Diego Augusto Santos , Asunta Piritta , Pozeriene Jurate , López-Gil José Francisco , Ng Kwok
Published: February 2023

The purpose was to synthesize information gathered from the interpretation and conclusion sections of the Global Matrix of Para Report Cards on the physical activity of children and adolescents with disabilities. The synthesis was based on the strengths, weaknesses, opportunities, and threats framework. The procedure consisted of three stages: (a) the application of the International Classification of Functioning, Disability and Health as the theoretical framework; (b) identifying and aligning Global Matrix indicators and benchmarks with the International Classification of Functioning, Disability and Health components through a Delphi approach; and (c) using content analysis to identify themes from specific report cards. Outcomes reveal that further attention toward including children and adolescents with disabilities in fitness assessments is needed as well as adapted assessment methods. Program availability, equipment and facilities, and professional training emerged as strengths but need further development to overcome weaknesses. Paralympic inspiration was an opportunity, whereas extreme weather conditions presented potential threats to physical activity participation among children and adolescents with disabilities.
A Systematic Review of Lower-Body Kinematic and Strength Factors Associated With Pitch Velocity in Adult Baseball Pitchers
Authors: Manzi Joseph E. , Yu Jonathan S. , Sudah Suleiman Y. , Wishman Mark , Quan Theodore , Koo Alexander , Kunze Kyle N. , Kew Michelle , Carr James B. , Fu Michael , Dines Joshua S.
Published: February 2023

Context: Ball velocity for baseball pitchers is influenced by a multitude of factors along the kinetic chain. While a vast amount of data currently exist exploring lower-extremity kinematic and strength factors in baseball pitchers, no previous study has systematically reviewed the available literature. Objective: The aim of this systematic review was to perform a comprehensive assessment of the available literature investigating the association between lower-extremity kinematic and strength parameters and pitch velocity in adult pitchers. Evidence Acquisition: Cross-sectional studies that investigated the association between lower-body kinematic and strength factors and ball velocity in adult pitchers were selected. A methodological index for nonrandomized studies checklist was used to evaluate the quality of all included studies. Evidence Synthesis: Seventeen studies met the inclusion criteria comprising a total of 909 pitchers (65%, professional, 33% college, and 3% recreational). The most studied elements were hip strength and stride length. The mean methodological index for nonrandomized studies score was 11.75 of 16 (range = 10–14). Pitch velocity was found to be influenced by several lower-body kinematic and strength factors including the following: (1) hip range of motion and strength of muscles around the hip and pelvis, (2) alterations in stride length, (3) alterations in lead knee flexion/extension, and (4) several pelvic and trunk spatial relationships throughout the throwing phase. Conclusions: Based on this review, we conclude that hip strength is a well-established predictor of increased pitch velocity in adult pitchers. Further studies in adult pitchers are needed to elucidate the effect of stride length on pitch velocity given mixed results across multiple studies. This study can provide a basis for trainers and coaches to consider the importance of lower-extremity muscle strengthening as a means by which adult pitchers can improve pitching performance.
Torus mandibularis and its implication as a risk factor for the formation of sialolithiasis
Authors: Shaver Timothy Brandon , Joshi Arjun S
Published: February 2023

Sialolithiasis is the formation of a stone within the salivary gland, and approximately 80% of them occur within the submandibular gland. Sialolithiasis can lead to swelling and pain of the gland in the immediate phase and if left untreated, can lead to sialadenitis and even atrophy of the gland. Certain factors have already been established in the formation of sialolithiasis such as dehydration, tobacco smoke, autoimmune disorders and certain medications. One factor we theorise contributes to the formation of sialolithiasis is bony outgrowths on the tongue surface of the jaw, called mandibular tori. These outgrowths can lead to external compression of the submandibular duct, which leads to impeded salivary flow and the potential for sialolith formation. We present two cases in which individuals had submandibular sialolithiasis in the setting of extensive mandibular tori.
Central visual field damage in glaucoma eyes with choroidal microvasculature dropout with and without high axial myopia
Authors: Micheletti Eleonora , El-Nimri Nevin , Nishida Takashi , Moghimi Sasan , Rezapour Jasmin , Fazio Massimo A , Suh Min Hee , Bowd Christopher , Belghith Akram , Christopher Mark , Jonas Jost B , Weinreb Robert N , Zangwill Linda M
Published: February 2023

Purpose

To characterise the relationship between a deep-layer microvasculature dropout (MvD) and central visual field (VF) damage in primary open-angle glaucoma (POAG) patients with and without high axial myopia.

Design

Cross-sectional study.

Methods

Seventy-one eyes (49 patients) with high axial myopia and POAG and 125 non-highly myopic POAG eyes (97 patients) were enrolled. Presence, area and angular circumference of juxtapapillary MvD were evaluated on optical coherence tomography angiography B-scans and en-face choroidal images.

Results

Juxtapapillary MvD was detected more often in the highly myopic POAG eyes (43 eyes, 86%) than in the non-highly myopic eyes (73 eyes, 61.9%; p=0.002). In eyes with MvD, MvD area and angular circumference (95% CI) were significantly larger in the highly myopic eyes compared with the non-highly myopic eyes (area: (0.69 (0.40, 0.98) mm2vs 0.31 (0.19, 0.42) mm2, p=0.011) and (angular circumference: 84.3 (62.9, 105.8) vs 74.5 (58.3, 90.9) degrees, p<0.001), respectively. 24-2 VF mean deviation (MD) was significantly worse in eyes with MvD compared with eyes without MvD in both groups (p<0.001). After adjusting for 24-2 MD VF, central VF defects were more frequently found in eyes with MvD compared with eyes without MvD (82.7% vs 60.9%, p<0.001). In multivariable analysis, higher intraocular pressure, worse 24-2 VF MD, longer axial length and greater MvD area and angular circumference were associated with worse 10-2 VF MD.

Conclusions

MvD was more prevalent and larger in POAG eyes with high myopia than in non-highly myopic POAG eyes. In both groups, eyes with MvD showed worse glaucoma severity and more central VF defects.
Implementation of the new WHO antenatal care model for a positive pregnancy experience: a monitoring framework
Authors: Lattof Samantha R , Moran Allisyn C , Kidula Nancy , Moller Ann-Beth , Jayathilaka Chandani Anoma , Diaz Theresa , Tunçalp Özge
Published: February 2023

Monitoring the implementation and impact of routine antenatal care (ANC), as described in the new World Health Organization (WHO) ANC model, requires indicators that go beyond the previously used global benchmark indicator of four or more ANC visits. To enable consistent monitoring of ANC content and care processes and to provide guidance to countries and health facilities, WHO developed an ANC monitoring framework. This framework builds on a conceptual framework for quality ANC and a scoping review of ANC indicators that mapped existing indicators related to recommendations in the new WHO ANC model. Based on the scoping review and following an iterative and consultative process, we developed a monitoring framework consisting of core indicators recommended for monitoring ANC recommendations in all settings, as well as a menu of additional measures. Finally, a research agenda highlights areas where ANC recommendations exist, but measures require further development. Nine core indicators can already be monitored globally and/or nationally, depending on the preferred data sources. Two core indicators (experience of care, ultrasound scan before 24 weeks) are included as placeholders requiring priority by the research agenda. Six context-specific indicators are appropriate for national and subnational monitoring in various settings based on specific guidance. Thirty-five additional indicators may be relevant and desirable for monitoring, depending on programme priorities. Monitoring implementation of the new WHO ANC model and the outcomes of routine ANC require greater attention to the measurement of ANC content and care processes as well as women’s experience of ANC.
Shortages and price variability of essential cytotoxic medicines for treating children with cancers
Authors: Martei Yehoda M , Iwamoto Kotoji , Barr Ronald D , Wiernkowski John T , Robertson Jane
Published: February 2023

Introduction

Low-income and middle-income countries (LMICs) face the largest burden of mortality from childhood cancers with limited access to curative therapies. Few comparative analyses across all income groups and world regions have examined the availability and acquisition costs of essential medicines for treating cancers in children.

Methods

A cross-sectional survey involved countries in five income groups—low-income (LIC), lower-middle-income (LMC), upper-middle-income (UMC), two high-income country groups (HIC1, HIC2). Physicians and pharmacists reported institutional use, availability, stock outs and prices (brand and generic products) of 34 essential medicines. Price comparisons used US$, applying foreign exchange rates (XR) and purchasing power parity (PPP) adjustments. Medicine costs for treating acute lymphoblastic leukaemia (ALL), Burkitt lymphoma (BL) and Wilms tumour (WT) were calculated (child 29 kg, body surface area 1 m2). Comparisons were conducted using non-parametric Kruskal-Wallis tests.

Results

Fifty-eight respondents (50 countries) provided information on medicine use, availability and stock outs, with usable price data from 42 facilities (37 countries). The extent of use of International Society of Paediatric Oncology core and ancillary medicines varied across income groups (p<0.0001 and p=0.0002 respectively). LMC and LIC facilities used fewer medicines than UMC and HIC facilities. UMC and LMC facilities were more likely to report medicines not available or stockouts.

Medicine prices varied widely within and between income bands; generic products were not always cheaper than brand equivalents. PPP adjustment showed relatively higher prices in UMC and LMC facilities for some medicines. Medicine costs were highest in HICs for ALL (p=0.0075 XR; p=0.0178 PPP-adjusted analyses) and WT (p =<0.0001 XR; p=0.0007 PPP-adjusted). Medicine costs for BL were not significantly different.

Conclusion

Problems with the availability of essential medicines, dependable supply chains, confidential medicine prices and wide variability in treatment costs contribute to persistent challenges in the care of children with treatable cancers, especially in LMICs.
The return of austerity imperils global health
Authors: Stubbs Thomas , Kentikelenis Alexandros , Gabor Daniela , Ghosh Jayati , McKee Martin
Published: February 2023

Recognising the world’s lack of preparedness for the COVID-19 pandemic, international organisations like the World Health Organization, World Bank, and International Monetary Fund are calling for extensive additional funding to strengthen pandemic preparedness and response systems in low-income and middle-income countries, including through domestic resource mobilisation. This article examines the prospects of national health budgets increasing in such a context, drawing on new International Monetary Fund projections on public spending around the world. We show that by 2024 public spending will be lower than the 2010s average for almost half of all low-income and middle-income countries. A key driver of this new wave of austerity is the dramatic increase in public spending dedicated to repaying external debt—underpinned by growing debt stocks, US interest rates rises, and commodity price hikes. As in earlier crises, the stage is set for a situation where population health deteriorates—via compound effects of the pandemic and widespread economic hardship—while public health services required to tackle increased need are facing steep cuts. We conclude by considering what can be done to avoid repeating the mistakes of the past.
Nurses’ understanding and management of iron deficiency in Australia: a cross-sectional, exploratory study
Authors: O'Sullivan Therese A , Jayasuriya Pradeep H , Tsalis Natalie , Calogero Nina , Manocha Ramesh
Published: February 2023

Objectives

To assess the experiences and knowledge of nurses in the area of iron deficiency.

Design

A cross-sectional, exploratory study using online survey.

Setting

Data were collected from nurses working at various primary, secondary and tertiary Australian health practices and organisations.

Participants

Australian nurses currently in practice.

Method

Australian nurses currently in practice were invited to complete an online survey about their work background, personal experiences with iron deficiency and iron-deficiency identification and treatment. The survey included a nine-item questionnaire to assess knowledge of iron-deficiency risk factors and biochemistry.

Results

A total of 534 eligible nurses participated in the survey. Participants were more likely to be female, aged 55–64 years, and working in general practice. Just under half (45.1%) reported being diagnosed with iron deficiency themselves. Unusual fatigue or tiredness was the most frequent symptom that alerted nurses to potential iron deficiency in patients (reported by 91.9% of nurses). Nurses who had participated in formal training around iron deficiency in the last 5 years demonstrated a significantly higher knowledge score (4.2±2.1) compared with those who had not or were not sure about their formal training status (3.7±1.9, p=0.035). Knowledge around the understanding of functional iron deficiency was limited.

Conclusions

Nurses report personal experiences of iron deficiency and show good knowledge of symptoms, demonstrating the potential for them to take a leading role in managing iron deficiency in patients. Educational programmes are required to address knowledge gaps and should be offered via various methods to accommodate a diverse nurse cohort. Our research highlights the potential for an expanded scope of practice for nurses in the primary care setting in the area of iron deficiency.
Cohort profile: the Utrecht Cardiovascular Cohort–Second Manifestations of Arterial Disease (UCC-SMART) Study–an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands
Authors: Castelijns Maria C , Helmink Marga A G , Hageman Steven H J , Asselbergs Folkert W , de Borst Gert J , Bots Michiel L , Cramer Maarten J , Dorresteijn Jannick A N , Emmelot-Vonk Marielle H , Geerlings Mirjam I , de Jong Pim A , van der Kaaij Niels P , Kappelle L Jaap , Lely A Titia , van der Meer Manon G , Mol Barend M , Nathoe Hendrik M , Onland-Moret N Charlotte , van Petersen Rutger B , Ruigrok Ynte M , van Smeden Maarten , Teraa Martin , Vandersteen Angela , Verhaar Marianne C , Westerink Jan , Visseren Frank L J
Published: February 2023

Purpose

The Utrecht Cardiovascular Cohort–Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date.

Participants

The UCC-SMART Study includes patients aged 18–90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima–media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee.

Findings to date

By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines.

Future plans

The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes.
Maternal death surveillance efforts: notification and review coverage rates in 30 low-income and middle-income countries, 2015–2019
Authors: Serbanescu Florina , Monet Jean-Pierre , Whiting-Collins Lillian , Moran A C , Hsia Jason , Brun Michel
Published: February 2023

Objective

Performance of maternal death surveillance and response (MDSR) relies on the system’s ability to identify and notify all maternal deaths and its ability to review all maternal deaths by a committee. Unified definitions for indicators to assess these functions are lacking. We aim to estimate notification and review coverage rates in 30 countries between 2015 and 2019 using standardised definitions.

Design

Repeat cross-sectional surveys provided the numerators for the coverage indicators; United Nations (UN)-modelled expected country maternal deaths provided the denominators.

Setting

30 low-income and middle-income countries responding to the Maternal Health Thematic Fund annual surveys conducted by the UN Population Fund between 2015 and 2019.

Outcome measures

Notification coverage rate (CRn) was calculated as the proportion of expected maternal deaths that were notified at the national level annually; review coverage rate (CRr) was calculated as the proportion of expected maternal deaths that were reviewed annually.

Results

The average annualCRnfor all countries increased from 17% in 2015 to 28% in 2019; the average annualCRrincreased from 8% to 13%. Between 2015 and 2019, 22 countries (73%) reported increases in theCRn—with an average increase of 20 (SD 18) percentage points—and 24 countries (80%) reported increases inCRrby 7 (SD 11) percentage points. Low values ofCRrcontrasts with country-published review rates, ranging from 46% to 51%.

Conclusion

MDSR systems that count and review all maternal deaths can deliver real-time information that could prompt immediate actions and may improve maternal health. Consistent and systematic documentation of MDSR efforts may improve national and global monitoring. Assessing the notification and review functions using coverage indicators is feasible, not affected by fluctuations in data completeness and reporting, and can objectively capture progress.
Evidence for the effectiveness of interventions to reduce mental health related stigma in the workplace: a systematic review
Authors: Tóth Mónika Ditta , Ihionvien Sarah , Leduc Caleb , Aust Birgit , Amann Benedikt L , Cresswell-Smith Johanna , Reich Hanna , Cully Grace , Sanches Sarita , Fanaj Naim , Qirjako Gentiana , Tsantila Fotini , Ross Victoria , Mathieu Sharna , Pashoja Arlinda Cerga , Arensman Ella , Purebl György
Published: February 2023

Objectives

Increasing access to mental health support is a key factor for treating mental disorders, however, important barriers complicate help-seeking, among them, mental health related stigma being most prominent. We aimed to systematically review the current evidence for interventions focusing on reducing stigma related to mental health problems in small and medium enterprises (SMEs).

Design

Systematic review with a focus on interventions targeting mental health related stigma in the workplace in accordance with PRISMA guidelines. The methodological quality of included articles was assessed using the Quality Assessment Tool for Quantitative Studies Scale.

Data sources

PubMed, Ovid Medline, PsycINFO, Scopus, and Cochrane databases and Google Scholar were searched from January 2010 until November 2022.

Eligibility criteria for selecting studies

We included experimental or quasi-experimental studies about workplace interventions aiming to reduce stigma, where the outcomes were measured in terms of stigmatisation against depression, anxiety and/or other mental health problems.

Data extraction and synthesis

Records were screened by two independent reviewers after inspecting titles and abstracts and a full-text read of the articles to assess whether they meet inclusion criteria. The results were synthesised narratively.

Results

We identified 22 intervention studies, 3 with high quality, 13 with moderate quality and 6 with weak quality. Only 2 studies included SMEs, but no study focused on SMEs exclusively . The mode of delivery of the intervention was face to face in 15 studies, online in 4 studies and mixed in 3 studies. We found a significant reduction in stigmatising attitudes in almost all studies (20/22), using 10 different instruments/scales. Effects seemed to be independent of company size. Online interventions were found to be shorter, but seemed to be as effective as face-to-face interventions.

Conclusions

Although we did not find interventions focusing exclusively on SMEs, it is likely that antistigma interventions also will work in smaller workplaces.

Trial registration

PROSPERO: ID: CRD42020191307
Preterm birth and stillbirth rates associated with socioeconomic disparities during COVID-19 pandemic: a population-based cross-sectional study
Authors: Aboulatta Laila , Kowalec Kaarina , Leong Christine , Delaney Joseph A , Falk Jamie , Alessi-Severini Silvia , Chateau Dan , Tan Qier , Kearns Katherine , Raimondi Christina , Vaccaro Christine , Lavu Alekhya , Haidar Lara , Peymani Payam , Eltonsy Sherif
Published: February 2023

Background

Conflicting evidence exists on the impact of the COVID-19 pandemic restrictions on preterm birth (PTB) and stillbirth rates. We aimed to evaluate changes in PTB and stillbirth rates before and during the pandemic period and assess the potential effect modification of socioeconomic status (SES).

Methods

Using the linked administrative health databases from Manitoba, Canada, we conducted a cross-sectional study among all pregnant women, comparing 3.5 years pre-pandemic (1 October 2016 to 29 February 2020) to the first year of the pandemic (1 March 2020 to 31 March 2021). We used generalised linear models to assess the quarterly rates of PTB (<37 weeks) and stillbirths. We calculated the predicted trends based on pre-pandemic period data. Finally, we evaluated the PTB and stillbirth rates among lower and higher SES pregnant women (average annual household income) using subgroup analysis and interaction models.

Results

We examined 70 931 pregnancies in Manitoba during the study period. The risk of PTB increased by 7.7% (95%CI 1.01 to 1.13) and stillbirths by 33% (95% CI 1.08 to 1.64) during the pandemic period. Following COVID-19 restrictions implemented in March 2020, there were increases in the quarterly rates of both PTB (immediate increase (β2)=1.37; p=0.0247) and stillbirths (immediate increase (β2)=0.12; p=0.4434). Among the lower income groups, the pandemic restrictions resulted in an immediate relative increase in PTB and stillbirth rates by 20.12% (immediate increase (β2)=3.17; p=0.0057) and 27.19% (immediate increase (β2)=0.48; p=0.0852). However, over the pandemic, the overall PTB rate significantly decreased as a rebound effect by 0.85% per quarter (p=0.0004), whereas the overall stillbirth rate did not decrease significantly (slope decrease (β3) =−0.01; p=0.8296) compared with the pre-pandemic period. The quarterly rates during the pandemic among the higher income group decreased by 0.39% (p=0.1296) for PTB and increased by 0.07% (p=0.1565) for stillbirth. We observed an effect modification by SES for PTB rates (p=0.047).

Conclusion

While the onset of COVID-19 pandemic restrictions was not associated with significant effects on stillbirth rates, we observed an immediate and rebound effect on PTB rates. The impact of COVID-19 on preterm birth was dependent on SES, with higher influence on families with lower SES. Further studies are needed to detect future trend changes during pandemic waves after 2021 and assess potential underlying mechanisms.
SAFFRON-103: a phase 1b study of the safety and efficacy of sitravatinib combined with tislelizumab in patients with locally advanced or metastatic non-small cell lung cancer
Authors: Zhao Jun , Yu Xinmin , Huang Dingzhi , Ma Zhiyong , Gao Bo , Cui Jiuwei , Chu Qian , Zhou Qing , Sun Meili , Day Daphne , Wu Jingxun , Pan Hongming , Wang Lifeng , Voskoboynik Mark , Wang Zhehai , Liu Yunpeng , Li Hui , Zhang Juan , Peng Yanyan , Wu Yi-Long
Published: February 2023

Background

Some patients with locally advanced/metastatic non-small cell lung cancer (NSCLC) respond poorly to anti-programmed cell death protein 1 (PD-1)/anti-programmed death-ligand 1 (PD-L1) treatments. Combination with other agents may improve the outcomes. This open-label, multicenter, phase 1b trial investigated the combination of sitravatinib, a spectrum-selective tyrosine kinase inhibitor, plus anti-PD-1 antibody tislelizumab.

Methods

Patients with locally advanced/metastatic NSCLC were enrolled (Cohorts A, B, F, H, and I; N=22–24 per cohort). Cohorts A and F included patients previously treated with systemic therapy, with anti-PD-(L)1-resistant/refractory non-squamous (cohort A) or squamous (cohort F) disease. Cohort B included patients previously treated with systemic therapy, with anti-PD-(L)1-naïve non-squamous disease. Cohorts H and I included patients without prior systemic therapy for metastatic disease, no prior anti-PD-(L)1/immunotherapy, with PD-L1-positive non-squamous (cohort H) or squamous (cohort I) histology. Patients received sitravatinib 120 mg orally one time per day plus tislelizumab 200 mg intravenously every 3 weeks, until study withdrawal, disease progression, unacceptable toxicity, or death. The primary endpoint was safety/tolerability among all treated patients (N=122). Secondary endpoints included investigator-assessed tumor responses and progression-free survival (PFS).

Results

Median follow-up was 10.9 months (range: 0.4–30.6). Treatment-related adverse events (TRAEs) occurred in 98.4% of the patients, with ≥Grade 3 TRAEs in 51.6%. TRAEs led to discontinuation of either drug in 23.0% of the patients. Overall response rate was 8.7% (n/N: 2/23; 95% CI: 1.1% to 28.0%), 18.2% (4/22; 95% CI: 5.2% to 40.3%), 23.8% (5/21; 95% CI: 8.2% to 47.2%), 57.1% (12/21; 95% CI: 34.0% to 78.2%), and 30.4% (7/23; 95% CI: 13.2% to 52.9%) in cohorts A, F, B, H, and I, respectively. Median duration of response was not reached in cohort A and ranged from 6.9 to 17.9 months across other cohorts. Disease control was achieved in 78.3–90.9% of the patients. Median PFS ranged from 4.2 (cohort A) to 11.1 months (cohort H).

Conclusions

In patients with locally advanced/metastatic NSCLC, sitravatinib plus tislelizumab was tolerable for most patients, with no new safety signals and overall safety profiles consistent with known profiles of these agents. Objective responses were observed in all cohorts, including in patients naïve to systemic and anti-PD-(L)1 treatments, or with anti-PD-(L)1 resistant/refractory disease. Results support further investigation in selected NSCLC populations.

Trial registration number

NCT03666143.
TCR-engineered adoptive cell therapy effectively treats intracranial murine glioblastoma
Authors: Schaettler Maximilian O , Desai Rupen , Wang Anthony Z , Livingstone Alexandra J , Kobayashi Dale K , Coxon Andrew T , Bowman-Kirigin Jay A , Liu Connor J , Li Mao , Bender Diane E , White Michael J , Kranz David M , Johanns Tanner M , Dunn Gavin P
Published: February 2023

Background

Adoptive cellular therapies with chimeric antigen receptor T cells have revolutionized the treatment of some malignancies but have shown limited efficacy in solid tumors such as glioblastoma and face a scarcity of safe therapeutic targets. As an alternative, T cell receptor (TCR)–engineered cellular therapy against tumor-specific neoantigens has generated significant excitement, but there exist no preclinical systems to rigorously model this approach in glioblastoma.

Methods

We employed single-cell PCR to isolate a TCR specific for the Imp3D81Nneoantigen (mImp3) previously identified within the murine glioblastoma model GL261. This TCR was used to generate the Mutant Imp3-Specific TCR TransgenIC (MISTIC) mouse in which all CD8 T cells are specific for mImp3. The therapeutic efficacy of neoantigen-specific T cells was assessed through a model of cellular therapy consisting of the transfer of activated MISTIC T cells and interleukin 2 into lymphodepleted tumor-bearing mice. We employed flow cytometry, single-cell RNA sequencing, and whole-exome and RNA sequencing to examine the factors underlying treatment response.

Results

We isolated and characterized the 3×1.1C TCR that displayed a high affinity for mImp3 but no wild-type cross-reactivity. To provide a source of mImp3-specific T cells, we generated the MISTIC mouse. In a model of adoptive cellular therapy, the infusion of activated MISTIC T cells resulted in rapid intratumoral infiltration and profound antitumor effects with long-term cures in a majority of GL261-bearing mice. The subset of mice that did not respond to the adoptive cell therapy showed evidence of retained neoantigen expression but intratumoral MISTIC T cell dysfunction. The efficacy of MISTIC T cell therapy was lost in mice bearing a tumor with heterogeneous mImp3 expression, showcasing the barriers to targeted therapy in polyclonal human tumors.

Conclusions

We generated and characterized the first TCR transgenic against an endogenous neoantigen within a preclinical glioma model and demonstrated the therapeutic potential of adoptively transferred neoantigen-specific T cells. The MISTIC mouse provides a powerful novel platform for basic and translational studies of antitumor T-cell responses in glioblastoma.
Postpartum relapse risk in multiple sclerosis: a systematic review and meta-analysis
Authors: Schubert Charlotte , Steinberg Lea , Peper Julia , Ramien Caren , Hellwig Kerstin , Köpke Sascha , Solari Alessandra , Giordano Andrea , Gold Stefan M , Friede Tim , Heesen Christoph , Rahn Anne Christin
Published: February 2023

The influence of pregnancy on the course of multiple sclerosis (MS) has long been controversial. While historical evidence suggests a substantial decline in relapse rates during pregnancy followed by a rebound in the postpartum period, more recent work yielded equivocal results. We performed a systematic review and meta-analysis on data from cohort studies to determine whether women with MS experience increased relapse rates after delivery. A systematic literature search was conducted in the databases MEDLINE and Epistemonikos on the topic ‘motherhood choice in MS’ in March 2022. We included cohort studies assessing the association between pregnancy and MS relapse activity defined by the annualised relapse rate after 3, 6, 9 and 12 months post partum. Furthermore, information about disease-modifying therapies (DMT) and breast feeding was considered, if available. 5369 publications were identified. Of these, 93 full-text articles on MS relapse activity during the postpartum period were screened. 11 studies including 2739 pregnancies were eligible. Women with MS showed a significantly increased relapse rate in the first 6 months post partum, compared with preconception with the incidence rate ratio (IRR) almost doubled in the first 3 months post partum (1.87, 95% CI 1.40 to 2.50). However, at 10–12 months post partum, the IRR decreased significantly (0.81, 95% CI 0.67 to 0.98). Subanalysis on influencing parameters suggested that preconceptional DMTs (IRR for highly-effective DMTs 2.76, 95% CI 1.34 to 5.69) and exclusive breast feeding (risk ratio 0.39, 95% CI 0.18 to 0.86) significantly influenced postpartum relapse risk. Increased postpartum annualised relapse rate and possible modifiers should be considered in counselling women with MS who are considering pregnancy.
Rheumatology and palliative care: needs and opportunities
Authors: Chan Kwok Ying , Yap Desmond Y H , Chung Ho Yin , Chan Tak Mao , Gill Harinder Singh Harry , Lau Chak Sing
Published: February 2023

Palliative care (PC) has expanded to medical conditions beyond its conventional scope of terminal malignancy and end-stage organ failure. This editorial showed our opinion in care model for the integration of PC into rheumatology and the growing needs of both rheumatology and PC services in view of increasing comorbidities and novel therapies. We anticipate an escalating demand for PC in this special group of patients who have concomitant long-standing systemic rheumatic diseases and age-related comorbidities. In addition, patients with advanced malignancy who develop rheumatological problems and require PC is also an emerging area of service need.
ABCA3-related interstitial lung disease beyond infancy
Authors: Li Yang , Seidl Elias , Knoflach Katrin , Gothe Florian , Forstner Maria Elisabeth , Michel Katarzyna , Pawlita Ingo , Gesenhues Florian , Sattler Franziska , Yang Xiaohua , Kroener Carolin , Reu-Hofer Simone , Ley-Zaporozhan Julia , Kammer Birgit , Krüger-Stollfuß Ingrid , Dinkel Julien , Carlens Julia , Wetzke Martin , Moreno-Galdó Antonio , Torrent-Vernetta Alba , Lange Joanna , Krenke Katarzyna , Rumman Nisreen , Mayell Sarah , Sismanlar Tugba , Aslan Ayse , Regamey Nicolas , Proesmans Marijke , Stehling Florian , Naehrlich Lutz , Ayse Kilinc , Becker Sebastian , Koerner-Rettberg Cordula , Plattner Erika , Manali Effrosyni D , Papiris Spyridon A , Campo Ilaria , Kappler Matthias , Schwerk Nicolaus , Griese Matthias
Published: February 2023

Background

The majority of patients with childhood interstitial lung disease (chILD) caused by pathogenic variants in ATP binding cassette subfamily A member 3 (ABCA3) develop severe respiratory insufficiency within their first year of life and succumb to disease if not lung transplanted. This register-based cohort study reviews patients with ABCA3 lung disease who survived beyond the age of 1 year.

Method

Over a 21-year period, patients diagnosed as chILD due to ABCA3 deficiency were identified from the Kids Lung Register database. 44 patients survived beyond the first year of life and their long-term clinical course, oxygen supplementation and pulmonary function were reviewed. Chest CT and histopathology were scored blindly.

Results

At the end of the observation period, median age was 6.3 years (IQR: 2.8–11.7) and 36/44 (82%) were still alive without transplantation. Patients who had never received supplemental oxygen therapy survived longer than those persistently required oxygen supplementation (9.7 (95% CI 6.7 to 27.7) vs 3.0 years (95% CI 1.5 to 5.0), p=0.0126). Interstitial lung disease was clearly progressive over time based on lung function (forced vital capacity % predicted absolute loss −1.1% /year) and on chest CT (increasing cystic lesions in those with repetitive imaging). Lung histology pattern were variable (chronic pneumonitis of infancy, non-specific interstitial pneumonia, and desquamative interstitial pneumonia). In 37/44 subjects, theABCA3sequence variants were missense variants, small insertions or deletions with in-silico tools predicting some residual ABCA3 transporter function.

Conclusion

The natural history of ABCA3-related interstitial lung disease progresses during childhood and adolescence. Disease-modifying treatments are desirable to delay such disease course.
Lessons from the implementation of a trauma center-based program to support primary care providers in managing opioids and pain after trauma hospitalization
Authors: Baldwin Laura-Mae , Katers Laura A , Sullivan Mark D , Gordon Debra B , James Adrienne , Tauben David J , Arbabi Saman
Published: February 2023

Background

Decreasing exposure to prescription opioids is critical to lowering risk of opioid misuse, overdose and opioid use disorder. This study reports a secondary analysis of a randomized controlled trial implementing an opioid taper support program directed to primary care providers (PCPs) of patients discharged from a level I trauma center to their homes distant from the center, and shares lessons for trauma centers in supporting these patients.

Methods

This longitudinal descriptive mixed-methods study uses quantitative/qualitative data from trial intervention arm patients to examine implementation challenges and outcomes: adoption, acceptability, appropriateness, feasibility, fidelity. In the intervention, a physician assistant (PA) contacted patients after discharge to review their discharge instructions and pain management plan, confirm their PCP’s identity and encourage PCP follow-up. The PA reached out to the PCP to review the discharge instructions and offer ongoing opioid taper and pain management support.

Results

The PA reached 32 of 37 patients randomized to the program. Of these 32, 81% discussed topics not targeted by the intervention (eg, social/financial). The PA identified and reached a PCP’s office for only 51% of patients. Of these, all PCP offices (100% adoption) received one to four consults (mean 1.9) per patient (fidelity). Few consults were with PCPs (22%); most were with medical assistants (56%) or nurses (22%). The PA reported that it was not routinely clear to patients or PCPs who was responsible for post-trauma care and opioid taper, and what the taper instructions were.

Conclusions

This level I trauma center successfully implemented a telephonic opioid taper support program during COVID-19 but adapted the program to allow nurses and medical assistants to receive it. This study demonstrates a critical need to improve care transition from hospitalization to home for patients discharged after trauma.

Level of evidence

Level IV.
Performance evaluation of high-dimensional quantum key distribution with single-photon detector based on avalanche photodiode
Authors: Li Dong-Dong , Tang Yan-Lin , Zhao Mei-Sheng , Tao Jun , Dai Yun-Qi , Zhou Lei , Tang Shi-Biao , Zhao Yong
Published: February 2023

The current theoretical analysis model for high-dimensional quantum key distribution (QKD) was developed without carefully considering the dead time and after-pulse of the single-photon detectors. Here, we propose a new model that accounts for these two effects. With this model, we analyze the effects of various properties of the single-photon detector on the performance of the high-dimensional quantum key distribution and show numerically that the high-dimensional quantum key distribution can be achieved up to 180 km with InGaAs/InP-type single-photon detectors. This work can improve our understanding of the factors that determine the performance of high-dimensional quantum key distribution and will help to promote the application of single-photon detectors based on avalanche photodiodes in high-dimensional quantum key distribution.
On assorted soliton wave solutions with the higher-order fractional Boussinesq–Burgers system
Authors: Zafar Asim , Ijaz Maliha , Qaisar Anoosha , Ahmad Daud , Bekir Ahmet
Published: February 2023

The purpose of this study is to highlight the shallow water wave patterns along the ocean shore or in lakes with the higher-order Boussinesq–Burgers system possessing a fractional derivative operator. A generic fractional transformation is used, which turns the proposed model into an nonlinear ordinary differential equations (NLODEs) system. For the construction of new solitons of the mentioned coupled system, the auxiliary equation technique is employed. This approach produced numerous soliton solutions such as bright, singular and w-shaped solitons of the aforesaid model successfully. These results are expressed graphically to exemplify their physical appearance with the help of soft computations in Mathematica. All the solutions yielded by this method are novel and have not been derived yet.
TH-iSSD: Design and Implementation of a Generic and Reconfigurable Near-Data Processing Framework
Authors: Shu Jiwu , Fang Kedong , Chen Youmin , Wang Shuo
Published: February 2023

We present the design and implementation of TH-iSSD, a near-data processing framework to address the data movement problem. TH-iSSD does not pose any restriction to the hardware selection and is highly reconfigurable—its core components, such as the on-device compute unit (e.g., FPGA, embedded CPUs) and data collectors (e.g., camera, sensors), can be easily replaced to adapt to different use cases. TH-iSSD achieves this goal by incorporating highly flexible computation and data paths. In the data path, TH-iSSD adopts an efficient device-level data switch that exchanges data with both host CPUs and peripheral sensors; it also enables direct accesses between the sensing, computation, and storage hardware components, which completely eliminates the redundant data movement overhead, and thus delivers both high performance and energy efficiency. In the computation path, TH-iSSD provides an abstraction offilestreamfor developers, which abstracts a collection of data along with the related computation task as a file. Since existing applications are familiar with POSIX-like interfaces, they can be ported on top of our platform with minimal code modification. Moreover, TH-iSSD also introduces mechanisms includingpipelined near-data processingandpriority-aware I/O schedulingto make TH-iSSD perform more effectively. We deploy TH-iSSD to accelerate two types of applications: the content-based information retrieval system and the edge zero-streaming system. Our experimental results show that TH-iSSD achieves up to 1.6× higher throughput and 36% lower latency thancompute-centricdesigns.