bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiphospholipid syndrome: advances in diagnosis, pathogenesis, and management
Authors: Knight Jason S , Branch D Ware , Ortel Thomas L
Published: February 2023

Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease propelled by circulating autoantibodies that recognize cell surface phospholipids and phospholipid binding proteins. The result is an increased risk of thrombotic events, pregnancy morbidity, and various other autoimmune and inflammatory complications. Although antiphospholipid syndrome was first recognized in patients with lupus, the stand alone presentation of antiphospholipid syndrome is at least equally common. Overall, the diagnosis appears to affect at least one in 2000 people. Studies of antiphospholipid syndrome pathogenesis have long focused on logical candidates such as coagulation factors, endothelial cells, and platelets. Recent work has shed light on additional potential therapeutic targets within the innate immune system, including the complement system and neutrophil extracellular traps. Vitamin K antagonists remain the mainstay of treatment for most patients with thrombotic antiphospholipid syndrome and, based on current data, appear superior to the more targeted direct oral anticoagulants. The potential role of immunomodulatory treatments in antiphospholipid syndrome management is receiving increased attention. As for many systemic autoimmune diseases, the most important future direction is to more precisely identify mechanistic drivers of disease heterogeneity in pursuit of unlocking personalized and proactive treatments for patients.
Brain changes in neuroimaging of adult patients with vitamin D deficiency: systematic review protocol
Authors: Porto Catarina Magalhães , Leão Rita de Cássia Hoffmann , Sousa Renata Alves de , Diniz Paula Rejane Beserra , Silva Tatiana de Paula Santana da , Sougey Everton Botelho
Published: February 2023

Introduction

Brain abnormalities detected through neuroimaging are described in patients with vitamin D deficiency, however, it is still not clear which cerebral alterations are more frequent and characteristic in this population. Thus, this review aims to identify and classify which are the main and most frequent brain changes found by neuroimaging in patients with vitamin D deficiency.

Methods and analysis

The study protocol was constructed in accordance with Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and the leading research question was formulated through Population, Intervention, Comparator, Outcome, Setting. The evidence will be researched at the following electronic databases: PubMed, PsycINFO, Scopus, Web of Science and EMBASE. Two researchers will work in the selection, analysis and inclusion phases of the articles. In the case of divergence, a third-party reviewer will be contacted. The following studies will be included: (1) cohort studies, case–control studies and cross-sectional studies; (2) studies carried out on patients with serum 25-hydroxyvitamin D levels below 30 ng/mL; (3) studies conducted with an adult population; (4) studies using neuroimaging methods. Articles considered eligible will be analysed by the Newcastle-Ottawa Quality Assessment Scale/cross-section studies to evaluate study quality. The survey will be conducted from June to December 2022.

Ethics and dissemination

The identification of the main and most frequent brain alterations found through neuroimaging in patients with vitamin D deficiency can guide professionals as to the identification which of the main cerebral pathologies detected through neuroimaging are related to vitamin D deficiency, in choosing more sensitive and specific neuroimaging tests to detect these brain changes, in addition to emphasising the importance of monitoring and maintaining adequate serum levels of vitamin D, in order to reduce possible cognitive sequelae. Results will be announced at national and international conferences.

PROSPERO registration number

CRD42018100074.
Protocol for the INFORMED (Individualised Patient Care and Treatment for Maternal Diabetes) Study: a randomised controlled trial embedded within routine care
Authors: Dingena Cassy F , Mahendra Anvesha , Holmes Melvin J , Clement Naomi S , Scott Eleanor M , Zulyniak Michael A
Published: February 2023

Introduction

Diabetes in pregnancy presents a unique physiological challenge to manage glycaemia while maintaining adequate nourishment for the growing fetus. Women with diabetes who become pregnant are at greater risk of adverse maternal and newborn outcomes, compared with women without diabetes. Evidence suggests that control of (postprandial) glycaemia is key to manage maternal and offspring health but it is not yet clear (1) how diet and lifestyle moderate these shifts across the full duration of pregnancy or (2) what aspects of maternal and offspring health are associated with dysglycaemia.

Methods and analysis

To investigate these gaps, a cross-over randomised clinical trial has been embedded within routine clinical care. Seventy-six pregnant women in their first trimester with type 1 or type 2 diabetes (with or without medication) attending their routine antenatal appointments at National Health Service (NHS) Leeds Teaching Hospitals will be recruited. Following informed consent, data on women’s health, glycaemia, pregnancy and delivery will be shared by the NHS with researchers. At each visit in the first (10–12 weeks), second (18–20 weeks) and third (28–34 weeks) trimester, participants will be asked for consent to: (1) lifestyle and diet questionnaires, (2) blood for research purposes and (3) analysis of urine collected at clinical visits. Additionally, participants will be asked to consume two blinded meals in duplicate in second and third trimester. Glycaemia will be assessed by continuous glucose monitoring as part of routine care. The primary outcome is the effect of experimental meals (high vs low protein) on postprandial glycaemia. Secondary outcomes include (1) the association between dysglycaemia and maternal and newborn health, and (2) the association between maternal metabolic profiles in early pregnancy with dysglycaemia in later pregnancy.

Ethics and dissemination

The Leeds East Research Ethics Committee and NHS (REC: 21/NE/0196) approved the study. Results will be published in peer-reviewed journals and disseminated to participants and the wider public.

Trial registration number

ISRCTN57579163.
School readiness of children at high risk of cerebral palsy randomised to early neuroprotection and neurorehabilitation: protocol for a follow-up study of participants from four randomised clinical trials
Authors: Boyd Roslyn N , Novak Iona , Morgan Catherine , Bora Samudragupta , Sakzewski Leanne , Ware Robert S , Comans Tracy , Fahey Michael Collingwood , Whittingham Koa , Trost Stewart , Pannek Kerstin , Pagnozzi Alex , Mcintyre Sarah , Badawi Nadia , Smithers Sheedy Hayley , Palmer Kirsten Rebecca , Burgess Andrea , Keramat Syed Afroz , Bell Kristie , Hines Ashleigh , Benfer Katherine , Wotherspoon Jane , Gascoigne-Pees Laura , Leishman Shaneen , Oftedal Stina
Published: February 2023

Introduction

School readiness includes cognitive, socio-emotional, language and physical growth and development domains which share strong associations with life-course opportunities. Children with cerebral palsy (CP) are at increased risk of poor school readiness compared with their typically developing peers. Recently, earlier diagnosis of CP has allowed interventions to commence sooner, harnessing neuroplasticity. First, we hypothesise that early referral to intervention for children at-risk of CP will lead to improved school readiness at 4–6 years relative to placebo or care as usual. Second, we hypothesise that receipt of early diagnosis and early intervention will lead to cost-savings in the form of reduced healthcare utilisation.

Methods and analysis

Infants identified as at-risk of CP ≤6 months corrected age (n=425) recruited to four randomised trials of neuroprotectants (n=1), early neurorehabilitation (n=2) or early parenting support (n=1) will be re-recruited to one overarching follow-up study at age 4–6 years 3 months. A comprehensive battery of standardised assessments and questionnaires will be administered to assess all domains of school readiness and associated risk factors. Participants will be compared with a historical control group of children (n=245) who were diagnosed with CP in their second year of life. Mixed-effects regression models will be used to compare school readiness outcomes between those referred for early intervention versus placebo/care-as-usual. We will also compare health-resource use associated with early diagnosis and intervention versus later diagnosis and intervention.

Ethics and dissemination

The Children’s Health Queensland Hospital and Health Service, The University of Queensland, University of Sydney, Monash University and Curtin University Human Research Ethics Committees have approved this study. Informed consent will be sought from the parent or legal guardian of every child invited to participate. Results will be disseminated in peer-reviewed journals, scientific conferences and professional organisations, and to people with lived experience of CP and their families.

Trial registration number

ACTRN12621001253897.
Derivation and validation of clinical prediction rules for diagnosis of infectious mononucleosis: a prospective cohort study
Authors: de Paor Muireann , Boland Fiona , Cai Xinyan , Smith Susan , Ebell Mark H , Mac Donncha Eoin , Fahey Tom
Published: February 2023

Objectives

Infectious mononucleosis (IM) is a clinical syndrome that is characterised by lymphadenopathy, fever and sore throat. Although generally not considered a serious illness, IM can lead to significant loss of time from school or work due to profound fatigue, or the development of chronic illness. This study aimed to derive and externally validate clinical prediction rules (CPRs) for IM caused by Epstein-Barr virus (EBV).

Design

Prospective cohort study.

Setting and participants

328 participants were recruited prospectively for the derivation cohort, from seven university-affiliated student health centres in Ireland. Participants were young adults (17–39 years old, mean age 20.6 years) with sore throat and one other additional symptom suggestive of IM. The validation cohort was a retrospective cohort of 1498 participants from a student health centre at the University of Georgia, USA.

Main outcome measures

Regression analyses were used to develop four CPR models, internally validated in the derivation cohort. External validation was carried out in the geographically separate validation cohort.

Results

In the derivation cohort, there were 328 participants, of whom 42 (12.8%) had a positive EBV serology test result. Of 1498 participants in the validation cohort, 243 (16.2%) had positive heterophile antibody tests for IM. Four alternative CPR models were developed and compared. There was moderate discrimination and good calibration for all models. The sparsest CPR included presence of enlarged/tender posterior cervical lymph nodes and presence of exudate on the pharynx. This model had moderate discrimination (area under the receiver operating characteristic curve (AUC): 0.70; 95% CI: 0.62–0.79) and good calibration. On external validation, this model demonstrated reasonable discrimination (AUC: 0.69; 95% CI: 0.67–0.72) and good calibration.

Conclusions

The alternative CPRs proposed can provide quantitative probability estimates of IM. Used in conjunction with serological testing for atypical lymphocytosis and immunoglobulin testing for viral capsid antigen, CPRs can enhance diagnostic decision-making for IM in community settings.
Piloting of a minimum data set for older people living in care homes in England: protocol for a longitudinal, mixed-methods study
Authors: Towers Ann-Marie , Gordon Adam , Wolters Arne Timon , Allan Stephen , Rand Stacey , Webster Lucy Anne , Crellin Elizabeth , Brine Richard James , De Corte Kaat , Akdur Gizdem , Irvine Lisa , Burton Jennifer , Hanratty Barbara , Killett Anne , Meyer Julienne , Jones Liz , Goodman Claire
Published: February 2023

Introduction

Health and care data are routinely collected about care home residents in England, yet there is no way to collate these data to inform benchmarking and improvement. The Developing research resources And minimum data set for Care Homes’ Adoption and use study has developed a prototype minimum data set (MDS) for piloting.

Methods and analysis

A mixed-methods longitudinal pilot study will be conducted in 60 care homes (approximately 960 residents) in 3 regions of England, using resident data from cloud-based digital care home records at two-time points. These will be linked to resident and care home level data held within routine National Health Service and social care data sets. Two rounds of focus groups with care home staff (n=8–10 per region) and additional interviews with external stakeholders (n=3 per region) will explore implementation and the perceived utility of the MDS. Data will be assessed for completeness and timeliness of completion. Descriptive statistics, including percentage floor and ceiling effects, will establish data quality. For validated scales, construct validity will be assessed by hypothesis testing and exploratory factor analysis will establish structural validity. Internal consistency will be established using Cronbach’s alpha. Longitudinal analysis of the pilot data will demonstrate the value of the MDS to each region. Qualitative data will be analysed inductively using thematic analysis to understand the complexities of implementing an MDS in care homes for older people.

Ethics and dissemination

The study has received ethical approval from the London Queen’s Square Research Ethics Committee (22/LO/0250). Informed consent is required for participation. Findings will be disseminated to: academics working on data use and integration in social care, care sector organisations, policy makers and commissioners. Findings will be published in peer-reviewed journals. Partner NIHR Applied Research Collaborations, the National Care Forum and the British Geriatrics Society will disseminate policy briefs.
National survey of Australian cardiac rehabilitation programmes: does current exercise programming adhere to evidence-based guidelines and best practice?
Authors: Hollings Matthew , Mavros Yorgi , Freeston Jonathan , Fiatarone Singh Maria
Published: February 2023

Objectives

The efficacy of exercise-based cardiac rehabilitation (CR) for patient outcomes is well established, with better outcomes when delivery meets recommended guidelines. The aim of this study was to assess how well Australian practice aligns with national CR guidelines for exercise assessment and prescription.

Method

This cross-sectional online survey was distributed to all 475 publicly listed CR services in Australia and consisted of four sections: (1) Programme and client demographics, (2) aerobic exercise characteristics, (3) resistance exercise characteristics and (4) pre-exercise assessment, exercise testing and progression.

Results

In total, 228 (54%) survey responses were received. Only three of five Australian guideline recommendations were consistently reported to be followed in current CR programmes: assessment of physical function prior to exercise (91%), prescription of light-moderate exercise intensity (76%) and review of referring physician results (75%). Remaining guidelines were commonly not implemented. For example, only 58% of services reported an initial assessment of resting ECG/heart rate, and only 58% reported the concurrent prescription of both aerobic and resistance exercise, which may have been influenced by equipment availability (p<0.05). Exercise-specific assessments such as muscular strength (18%) and aerobic fitness (13%) were uncommonly reported, although both were more frequent in metropolitan services (p<0.05) or when an exercise physiologist was present (p<0.05).

Conclusions

Clinically relevant deficits in national CR guideline implementation are common, potentially influenced by location, exercise supervisor and equipment availability. Key deficiencies include the lack of concurrent aerobic and resistance exercise prescription and infrequent assessment of important physiological outcomes including resting heart rate, muscular strength and aerobic fitness.
Lifestyle physical activity and rapid-rate non-sustained ventricular tachycardia in arrhythmogenic cardiomyopathy
Authors: Ramos-Maqueda Javier , Migueles Jairo H , Molina-Jiménez María , Ruiz-González David , Cabrera-Borrego Eva , Ruiz Salas Amalio , Soriano-Maldonado Alberto , Jimenez-Jaimez Juan
Published: February 2023

Objective

To investigate the association of accelerometer-measured lifestyle physical activity with rapid-rate non-sustained ventricular tachycardias (RR-NSVTs) in patients with arrhythmogenic cardiomyopathy (AC).

Methods

This multicentre, observational study enrolled 72 patients with AC, including right, left and biventricular forms of the disease, with underlying desmosomal and non-desmosomal mutations. Lifestyle physical activity, objectively monitored with accelerometers (ie, movement sensors) and RR-NSVT, identified as >188 bpm and >18 beats from a textile Holter ECG for 30 days.

Results

Sixty-three patients with AC (38±17.6 years, 57% men) were included. A total of 17 patients experienced ≥1 RR-NSVTs, and a total of 35 events were recorded. The odds of occurrence of ≥1 RR-NSVT during the recording did not increase as a function of either total physical activity (OR 0.95, 95% CI (CI95%) 0.68 to 1.30 for 60 min increase) or moderate-to-vigorous activities (OR 0.89, CI95%0.71 to 1.08 for 5 min increase). Participants presenting RR-NSVTs during the recording (n=17) did not present greater odds of RR-NSVT in the days with more time either in total physical activity (OR 1.05, CI95%0.84 to 1.29 for additional 60 min) or moderate-to-vigorous activities (OR 1.05, CI95%0.97 to 1.12 for additional 5 min). Physical activity levels were neither different between the patients with and without RR-NSVTs during the recording period nor in the days of occurrence of RR-NSVT compared with the rest of the days. Finally, 4 of the 35 RR-NSVTs recorded in the 30 days occurred during physical activity (3 during moderate-to-vigorous intensity and 1 during light-intensity activities).

Conclusions

These findings suggest that lifestyle physical activity is not associated with RR-NSVTs in patients with AC.
Downregulation of phosphoserine phosphatase potentiates tumor immune environments to enhance immune checkpoint blockade therapy
Authors: Peng Zhi-Peng , Liu Xing-Chen , Ruan Yong-Hao , Jiang Da , Huang Ai-Qi , Ning Wan-Ru , Jiang Ze-Zhou , Zheng Limin , Wu Yan
Published: February 2023

Background

Effects of immune checkpoint blockade (ICB) treatment in hepatocellular carcinoma (HCC) are limited. The current study explored the possibility of exploiting tumor metabolic switches to enhance HCC sensitivity to immune therapies.

Methods

Levels of one-carbon (1C) metabolism and the expression of phosphoserine phosphatase (PSPH), an upstream enzyme of 1C pathway, were evaluated in paired non-tumor and tumor tissues from HCC. Underlying mechanisms mediating the role of PSPH in regulating the infiltration of monocytes/macrophages and CD8+T lymphocytes were studied through both in vitro and in vivo experiments.

Results

PSPH was significantly upregulated in tumor tissues of HCC and its levels were positively correlated with disease progression. PSPH knockdown inhibited tumor growth in immunocompetent mice, but not in those with macrophage or T lymphocyte deficiencies, indicating the pro-tumor effects of PSPH were dependent on both immune components. Mechanistically, PSPH facilitated monocytes/macrophages infiltration by inducing the production of C-C motif chemokine 2 (CCL2), while at the same time reduced CD8+T lymphocytes recruitment through inhibiting the production of C-X-C Motif Chemokine 10 (CXCL10) in tumor necrosis factor alpha (TNF-α)-conditioned cancer cells. Glutathione and S-adenosyl-methionine were partially involved in regulating the production of CCL2 and CXCL10, respectively. shPSPH(short hairpin RNA) transfection of cancer cells enhanced tumor sensitivity to anti-programmed cell death protein 1 (PD-1) therapy in vivo, and interestingly, metformin could inhibit PSPH expression in cancer cells and mimic the effects of shPSPHin sensitizing tumors to anti-PD-1 treatment.

Conclusions

By tilting the immune balance towards a tumor-friendly composition, PSPH might be useful both as a marker in stratifying patients for ICB therapy, and as an attractive therapeutic target in the treatment of human HCC.
Oral health and functional outcomes following mechanical thrombectomy for ischemic stroke
Authors: Feldman Michael J , Koester Stefan W , Chaliff Ryan S , Yengo-Kahn Aaron , Wong Gunther , Roth Steven , Longo Michael , Fusco Matthew R , Froehler Michael T , Chitale Rohan
Published: February 2023

Background

An association between poor dentition and the risk of ischemic stroke has previously been reported in the literature. In this study we assessed oral hygiene (OH), including tooth loss and the presence of dental disease, to determine if an association exists with functional outcomes following mechanical thrombectomy (MT) for large-vessel ischemic stroke.

Methods

A retrospective review was conducted of consecutive adult patients at a single comprehensive stroke center who underwent MT from 2012 to 2018. Inclusion criteria included availability of CT imaging to radiographically assess OH. A multivariate analysis was performed, with the primary outcome being 90-day post-thrombectomy modified Rankin Scale (mRS) score >2.

Results

A total of 276 patients met the inclusion criteria. The average number of missing teeth was significantly higher in patients with a poor functional outcome (mean (SD) 10 (11) vs 4 (6), p<0.001). The presence of dental disease was associated with poor functional outcome, including cavities (21 (27%) vs 13 (8%), p<0.001), periapical infection (18 (23%) vs 11 (6.7%), p<0.001), and bone loss (27 (35%) vs 11 (6.7%), p<0.001). Unadjusted, missing teeth was a univariate predictor of poor outcome (OR 1.09 (95% CI 1.06 to 1.13), p<0.001). After adjustment for recanalization scores and use of tissue plasminogen activator (tPA), missing teeth remained a predictor of poor outcome (OR 1.07 (95% CI 1.03 to 1.11), p<0.001).

Conclusion

Missing teeth and the presence of dental disease are inversely correlated with functional independence following MT, independent of thrombectomy success or tPA status.
Decompression alone versus decompression with instrumented fusion in the treatment of lumbar degenerative spondylolisthesis: a systematic review and meta-analysis of randomised trials
Authors: Kaiser Radek , Kantorová Lucia , Langaufová Alena , Slezáková Simona , Tučková Dagmar , Klugar Miloslav , Klézl Zdeněk , Barsa Pavel , Cienciala Jan , Hajdúk Richard , Hrabálek Lumír , Kučera Roman , Netuka David , Prýmek Martin , Repko Martin , Smrčka Martin , Štulík Jan
Published: February 2023

Objective

To determine the efficacy of adding instrumented spinal fusion to decompression to treat degenerative spondylolisthesis (DS).

Design

Systematic review with meta-analysis.

Data sources

MEDLINE, Embase, Emcare, Cochrane Library, CINAHL, Scopus, ProQuest Dissertations & Theses Global, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform from inception to May 2022.

Eligibility criteria for study selection

Randomised controlled trials (RCTs) comparing decompression with instrumented fusion to decompression alone in patients with DS. Two reviewers independently screened the studies, assessed the risk of bias and extracted data. We provide the Grading of Recommendations, Assessment, Development and Evaluation assessment of the certainty of evidence (COE).

Results

We identified 4514 records and included four trials with 523 participants. At a 2-year follow-up, adding fusion to decompression likely results in trivial difference in the Oswestry Disability Index (range 0–100, with higher values indicating greater impairment) with mean difference (MD) 0.86 (95% CI −4.53 to 6.26; moderate COE). Similar results were observed for back and leg pain measured on a scale of 0 to 100, with higher values indicating more severe pain. There was a slightly increased improvement in back pain (2-year follow-up) in the group without fusion shown by MD −5·92 points (95% CI −11.00 to −0.84; moderate COE). There was a trivial difference in leg pain between the groups, slightly favouring the one without fusion, with MD −1.25 points (95% CI −6.71 to 4.21; moderate COE). Our findings at 2-year follow-up suggest that omitting fusion may increase the reoperation rate slightly (OR 1.23; 0.70 to 2.17; low COE).

Conclusions

Evidence suggests no benefits of adding instrumented fusion to decompression for treating DS. Isolated decompression seems sufficient for most patients. Further RCTs assessing spondylolisthesis stability are needed to determine which patients would benefit from fusion.

PROSPERO registration number

CRD42022308267.
Phosphorylated signal transducer and activator of transcription proteins 1 in salivary glandular tissue: an important histological marker for diagnosis of primary Sjögren’s syndrome
Authors: Zheng Qing , Liu Lingyu , Wang Bin , He Yan , Zhang Mengqin , Shi Guixiu
Published: February 2023

Objectives

The pathological diagnostic criteria for primary Sjögren’s syndrome (SjS) have certain limitations. We first explored the key pathogenic pathways of SjS through a bioinformatics approach, and then evaluated the diagnostic value of the important biomarker in SjS.

Methods

Transcriptome data from non-SjS controls and patients with SjS were analysed using integrated bioinformatics methods. In a case–control study, phosphorylated signal transducer and activator of transcription proteins 1 (p-STAT1), a key biomarker for the activation of interferon (IFN) pathway, was selected to evaluate its diagnostic value by immunohistochemical analyses in salivary gland (SG) tissues.

Results

The IFN-related pathways were aberrantly activated in patients with SjS. Positive staining of p-STAT1 was detected in the SjS group, but not in non-SjS control group. There was a significant difference in the integrated optical density values of p-STAT1 expressions between the controls and the SjS groups, as well as between the controls and the SjS lymphatic foci-negative groups (p<0.05). The area under the curve of the receiver operating characteristic curve for p-STAT1 was 0.990 (95% CI 0.969 to 1.000). There was a significant difference in both accuracy and sensitivity of p-STAT1 compared with the Focus Score (p<0.05). The Jorden index for p-STAT1 was 0.968 (95% CI 0.586 to 0.999).

Conclusions

The IFN pathway is the key pathogenic pathway in SjS. p-STAT1 may serve as an important biomarker, in addition to lymphocytic infiltration, to diagnose SjS. Particularly in SG samples with negative lymphatic foci, p-STAT1 confers pathological diagnostic value.
Prevalence and risk factors of osteonecrosis of the femoral head in patients with ANCA-associated vasculitis: a multicentre cohort study
Authors: Mimura Norihiro , Iwamoto Taro , Furuta Shunsuke , Ikeda Kei , Kobayashi Yoshihisa , Nakamura Takayuki , Saku Aiko , Kagami Shin-Ichiro , Matsuki Ayako , Takahashi Kentaro , Umibe Takeshi , Nakagomi Daiki , Sanayama Yoshie , Sugimoto Toyohiko , Fukuta Masashi , Hiraguri Masaki , Kawashima Hirotoshi , Hirose Koichi , Takatori Hiroaki , Suehiro Kenichi , Takahashi Shigekazu , Tamachi Tomohiro , Kato Manami , Takizawa Fumiyoshi , Kawarai Yuya , Hagiwara Shigeo , Nakamura Junichi , Ohtori Seiji , Nakajima Hiroshi
Published: February 2023

Objective

We aimed to determine the prevalence and risk factors for osteonecrosis of the femoral head (ONFH) in a multicentre cohort of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods

One hundred and eighty-six AAV patients who underwent radiographs and MRI screening of bilateral hip joints at more than 6 months after initial remission induction therapy (RIT) were retrospectively assessed for the presence of ONFH.

Results

Among 186 AAV patients, 33 (18%) were diagnosed with ONFH. Among the patients with ONFH, 55% were asymptomatic and 64% had bilateral ONFH. Seventy-six per cent of ONFH joints were in precollapse stages (stage ≤2), whereas 24% of ONFH joints were in collapse stages (stage ≥3). Moreover, 56% of the precollapse stage joints were already at risk of future collapse (type ≥C-1). Even in asymptomatic ONFH patients, 39% of the precollapse stage joints were type ≥C-1. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH in AAV patients (OR 1.072, 95% CI 1.017 to 1.130, p=0.009). Rituximab use was a significant beneficial factor against ONFH (p=0.019), but the multivariate analysis rejected its significance (p=0.257).

Conclusion

Eighteen per cent of AAV patients developed ONFH, and two-thirds of the ONFH joints were already in collapse stages or at risk of future collapse. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH. A rapid reduction of glucocorticoids in RIT and early detection of precollapse ONFH by MRI may decrease and intervene ONFH development in AAV patients.
Association of palliative care and hospital outcomes among solid tumour oncology inpatients
Authors: Im James HB , Chow Ronald , Novosel Madison , Xiang Jenny , Strait Michael , Rao Vinay , Kapo Jennifer , Zimmermann Camilla , Prsic Elizabeth
Published: February 2023

Objectives

We aimed to explore the association between receiving an inpatient palliative care consultation and hospital outcomes, including in-hospital death, intensive care unit (ICU) use, discharge to hospice, 30-day readmissions and 30-day emergency department (ED) visits.

Methods

We conducted a retrospective chart review of Yale New Haven Hospital medical oncology admissions from January 2018 through December 2021, with and without inpatient palliative care consultations. Hospital outcome data were extracted from medical records and operationalised as binary. Multivariable logistic regression was used to estimate ORs for the association between number of inpatient palliative care consultations and hospital outcomes.

Results

Our sample included 19 422 patients. Age, Rothman Index, site of malignancy, length of stay, discharge to hospice, ICU admissions, hospital death and readmissions within 30 days differed significantly between patients who received versus did not receive a palliative care consultation. On multivariable analysis, receiving one additional palliative care consultation was significantly associated with higher odds of hospital death (adjusted OR=1.15, 95% CI 1.12 to 1.17) and discharge to hospice (adjusted OR = 1.23, 95% CI 1.20 to 1.26), and lower odds of ICU admission (adjusted OR=0.94, 95% CI 0.92 to 0.97). There was no significant association between palliative care consultations and readmission within 30 days or with ED visits within 30 days.

Conclusion

Inpatients receiving palliative care had increased likelihood of hospital death. However, when controlling for significant differences in patient presentation, patients had nearly 25% greater odds of discharge to hospice and less odds to transition to ICU level of care.
Planetary population synthesis and the emergence of four classes of planetary system architectures
Authors: Emsenhuber Alexandre , Mordasini Christoph , Burn Remo
Published: February 2023

Planetary population synthesis is a helpful tool to understand the physics of planetary system formation. It builds on a global model, meaning that the model has to include a multitude of physical processes. The outcome can be statistically compared with exoplanet observations. Here, we review the population synthesis method and then use one population computed using the Generation III Bern model to explore how different planetary system architectures emerge and which conditions lead to their formation. The emerging systems can be classified into four main architectures: Class I of near in situ compositionally ordered terrestrial and ice planets, Class II of migrated sub-Neptunes, Class III of mixed low-mass and giant planets, broadly similar to the Solar System, and Class IV of dynamically active giants without inner low-mass planets. These four classes exhibit distinct typical formation pathways and are characterised by certain mass scales. We find that Class I forms from the local accretion of planetesimals followed by a giant impact phase, and the final planet masses correspond to what is expected from such a scenario, the ‘Goldreich mass’. Class II, the migrated sub-Neptune systems form when planets reach the ‘equality mass’ where accretion and migration timescales are comparable before the dispersal of the gas disc, but not large enough to allow for rapid gas accretion. Giant planets form when the ‘equality mass’ allows for gas accretion to proceed while the planet is migrating, i.e. when the critical core mass is reached. The main discriminant of the four classes is the initial mass of solids in the disc, with contributions from the lifetime and mass of the gas disc. The distinction between mixed Class III systems and Class IV dynamically active giants is in part due to the stochastic nature of dynamical interactions, such as scatterings between giant planets, rather than the initial conditions only. The breakdown of system into classes allows to better interpret the outcome of a complex model and understand which physical processes are dominant. Comparison with observations reveals differences to the actual population, pointing at limitation of theoretical understanding. For example, the overrepresentation of synthetic super-Earths and sub-Neptunes in Class I systems causes these planets to be found at lower metallicities than in observations.
Dissecting American Fuzzy Lop – A FuzzBench Evaluation - RCR Report
Authors: Fioraldi Andrea , Mantovani Alessandro , Maier Dominik , Balzarotti Davide
Published: February 2023

This report describes the artifacts of the “Dissecting American Fuzzy Lop – A FuzzBench Evaluation” paper. The artifacts are available online at
https://github.com/eurecom-s3/dissecting_afl
and archived at
https://doi.org/10.6084/m9.figshare.21401280
. American Fuzzy Lop (AFL) consists of the produced code, the setup to run the experiments in FuzzBench, and the generated reports. We claim the Functional badge as the patches to AFL are easy to enable and the experiments are easy to run thanks to the FuzzBench service, but the evaluations are self-contained and the modifications to AFL are as is. For the purpose of reproducing the experiments, no particular skills are needed as the process is straightforward and described in
https://google.github.io/fuzzbench/getting-started/adding-a-new-fuzzer/#requesting-an-experiment
.
The Price of Anarchy of Two-Buyer Sequential Multiunit Auctions
Authors: Ahunbay Mete Şeref , Vetta Adrian
Published: February 2023

We study the efficiency of first-/second-price sequential multiunit auctions with two buyers and complete information. Extending the primal-dual framework for obtaining efficiency bounds to this sequential setting, we obtain tight price of anarchy bounds. For general valuation functions, we show that the
price of anarchy
is exactly
1/T
for auctions with
T
items for sale. For concave valuation functions, we show that the price of anarchy is bounded below by
1-1/e≃ 0.632
. This bound is asymptotically tight as the number of items sold tends to infinity.
Optimal Pattern Retargeting in IEEE 1687 Networks: A SAT-based Upper-Bound Computation
Authors: Ibrahim Abrar A. , Ibrahim Ahmed M. Y. , El-Kharashi Mohamed Watheq , Safar Mona
Published: February 2023

A growing number of embedded instruments is being integrated into System-on-Chips for testing, monitoring, and several other purposes. To standardize their access protocols, the IEEE 1687 (IJTAG) standard has defined a flexible network infrastructure. Finding the shortest path in such networks requires a comprehensive search over a solution space, bounded by a limited number of time frames. This bound must be selected carefully, as it can neither be too large (to avoid unnecessary long execution time) nor too small (to avoid missing the optimal solution). Previous work was not efficiently applicable to all segments of IJTAG networks, with some providing unrealistic bounds and others having scope limitations or scalability issues. In this work, we present a new methodology for computing the upper-bound on the number of time frames using the Boolean Satisfiability Problem (SAT). Our proposed technique can also be customized to perfectly adapt to instruments access procedures, which in turn increases efficiency by reducing the time spent searching for required configurations. Results show the effectiveness of our work in computing the upper-bound for irregular benchmarks that are not constrained by a specific network design. This is achieved with a controlled increase in execution time, in contrast to previous work.
Towards LDPC Read Performance of 3D Flash Memories with Layer-induced Error Characteristics
Authors: Du Yajuan , Huang Siyi , Zhou Yao , Li Qiao
Published: February 2023

3D flash memories have been widely developed to further increase the storage capacity of SSDs by vertically stacking multiple layers. However, this special physical structure brings new error characteristics. Existing studies have discovered that there exist significant Raw Bit Error Rate (RBER) variations among different layers and RBER similarity inside the same layer due to the manufacturing process. These error characteristics would introduce a new data reliability issue. Currently, Low-Density Parity-Check (LDPC) code has been widely used to ensure the data reliability of flash memories. It can provide stronger error correction capability for high RBERs by trading with longer read latency. Traditional LDPC codes designed for planar flash memories do not consider the layer RBER characteristics of 3D flash memories, which may induce sub-optimal read performance.

This article first investigates the effect of RBER characteristics of 3D flash memories on read performance and then obtains two observations. On one hand, we observe that LDPC read latencies are largely diverse in different flash layers and increase in diverse speeds along with data retention. This phenomenon is caused by the inter-layer RBER variation. On the other hand, we also compare RBERs between different pages of the same flash layer and observe that read latencies with LDPC codes are quite similar, which is caused by the intra-layer RBER similarity. Then, by exploiting these two observation results, this article proposes a Multi-Granularity LDPC (MG-LDPC) read method to adapt read latency increase characteristics across 3D flash layers. In detail, we design five LDPC decoding engines with varied read level increase granularity (higher level induces higher latency) and assign these engines to each layer dynamically according to prior information, or in a fixed way. A series of experimental results demonstrate that the fixed and dynamic MG-LDPC methods can reduce SSD read response time by 21% and 51% on average, respectively.
Hindbrain ghrelin and liver-expressed antimicrobial peptide 2, ligands for growth hormone secretagogue receptor, bidirectionally control food intake
Authors: Wald Hallie S. , Ghidewon Misgana Y. , Hayes Matthew R. , Grill Harvey J.
Published: February 2023

Hindbrain growth hormone secretagogue receptor (GHSR) agonism increases food intake, yet the underlying neural mechanisms remain unclear. The functional effects of hindbrain GHSR antagonism by its endogenous antagonist liver-expressed antimicrobial peptide 2 (LEAP2) are also yet unexplored. To test the hypothesis that hindbrain GHSR agonism attenuates the food intake inhibitory effect of gastrointestinal (GI) satiation signals, ghrelin (at a feeding subthreshold dose) was administered to the fourth ventricle (4V) or directly to the nucleus tractus solitarius (NTS) before systemic delivery of the GI satiation signal cholecystokinin (CCK). Also examined, was whether hindbrain GHSR agonism attenuated CCK-induced NTS neural activation (c-Fos immunofluorescence). To investigate an alternate hypothesis that hindbrain GHSR agonism enhances feeding motivation and food seeking, intake stimulatory ghrelin doses were administered to the 4V and fixed ratio 5 (FR-5), progressive ratio (PR), and operant reinstatement paradigms for palatable food responding were evaluated. Also assessed were 4V LEAP2 delivery on food intake and body weight (BW) and on ghrelin-stimulated feeding. Both 4V and NTS ghrelin blocked the intake inhibitory effect of CCK and 4V ghrelin blocked CCK-induced NTS neural activation. Although 4V ghrelin increased low-demand FR-5 responding, it did not increase high-demand PR or reinstatement of operant responding. Fourth ventricle LEAP2 reduced chow intake and BW and blocked hindbrain ghrelin-stimulated feeding. Data support a role for hindbrain GHSR in bidirectional control of food intake through mechanisms that include interacting with the NTS neural processing of GI satiation signals but not food motivation and food seeking.
Comparative Pharmacokinetic Study of 5 Active Ingredients after Oral Administration of Zuogui Pill in Osteoporotic Rats with Different Syndrome Types
Authors: Qiu Jiawei , Zhu Yaoyao , Xing Jing , Wang Ling , Zhang Jianhua , Yin Hua
Published: February 2023

Zuogui Pill is a kidney-yin-tonifying formula in traditional Chinese medicine that is widely used to manage osteoporosis with kidney-yin-deficiency in China. Herein, an efficient and accurate high-performance liquid chromatography-tandem mass spectrometry method was developed to determine the concentrations of 5 bioactive compounds in rat plasma following oral administration of Zuogui Pill. Because drug absorption and distribution differ under physiological and pathological conditions, the established method was used to quantify blood components and dynamic change in osteoporotic rats with different syndrome types. Moreover, integrated pharmacokinetic study was conducted to describe the overall pharmacokinetic characteristics of traditional Chinese medicine. The results showed that the absorption, distribution, and metabolism of Zuogui Pill varied widely under different states. The bioavailability of most active components showed significant advantages in osteoporotic rats with kidney-yin-deficiency, which corresponds to the opinion that Zuogui Pill has the effect of nourishing kidney-yin. It is hoped that this finding could interpret the pharmacodynamic substances and mechanism of Zuogui Pill in the treatment of osteoporosis with kidney-yin-deficiency.
Amelioration Effect of Fly Ash and Powdered Ground Steel Slag for Improving Expansive Subgrade Soil
Authors: Alemshet Dereje , Fayissa Basha , Geremew Anteneh , Chala Gelata
Published: February 2023

The utilization of fly ash (FA) and powdered granulated steel slag (PGSS) as additives in soil stabilization plays a crucial role in environmental, economic, and weak soil property improving advantages. In this study, the combined effect of FA and PGSS in improving expansive subgrade soil was investigated. The materials used for this study were expansive soils, FA, and PGSS. The study has applied an experimental research method. For this investigation, the index properties, Free Swell Index (FSI), unconfined compressive strength (UCS), optimum moisture content (OMC), California bearing ratio (CBR), and scanning electron microscope (SEM) tests were done for treated and untreated expansive soils. The findings indicated that as the mixture of FA (0 to 12.5% at 5% increment) and PGSS (0 to 25% at 5% at 2.5% increment) is added to the untreated expansive soils, the index properties, FSI, and OMC of the soils were significantly declined. The CBR values of expansive soils containing 20% FA and 10% PGSS mixture were 13.8% and 16.21%, respectively, which improved the quality of the soils by 85.43% and 84.82%, respectively. While the untreated expansive soils have a UCS value of 0.34 kg/cm2, the treated soil comprising 20% FA and 10% PGSS mixture has a UCS value of 13.42 kg/cm2, indicating that the soil strength is enhanced by 97.47%. The results of the studies demonstrate that adding FA and PGSS to expansive soil improves its stability and strength. The study concluded that disposals such as FA and PGSS might be effectively used in enhancing the characteristics of construction materials and used for the construction.
Sublethal Effects of Cadmium on the Osmoregulatory and Acid-Base Parameters of Tilapia (Oreochromis niloticus) at Various Times
Authors: Soegianto Agoes , Yulianto Bambang , Payus Carolyn Melissa , Affandi Moch , Mukholladun Wildanun , Indriyasari Khudrotul Nisa , Marchellina Ary , Rahmatin Nailul Muthiati
Published: February 2023

Background. Cadmium (Cd) can contaminate aquatic environments as a result of anthropogenic activity. Cd accumulates quickly in the tissues of fish and has the potential to affect their physiology, including osmoregulation and acid-base balance. Therefore, the purpose of this study was to examine the sublethal effects of Cd on the osmoregulation and acid-base balance of tilapia Oreochromis niloticus at different times. Methods. Fish were exposed to sublethal concentrations of Cd (1 and 2 mg/L) for 4 and 15 days. At the end of the experiment, fish were collected from each treatment to examine the levels of Cd and carbonic anhydrase (CA) in the gills, plasma osmolality, ions, blood pH, pCO2, pO2, and hematological parameters. Results. Cd concentrations in gills rose with increasing Cd concentrations in the medium and exposure time. Cd inhibited respiration by generating metabolic acidosis, decreasing gill CA, reducing pO2, plasma osmolality, Cl−, and K+, particularly at 2 mg/L for 4 days and 1 and 2 mg/L for 15 days. Red blood cell (RBC), hemoglobin (Hb), and hematocrit (Ht) levels decreased as Cd levels in water and exposure duration increased. Conclusion. Cd inhibits respiration, lowers RCB, Hb, and Ht levels and decreases ionic and osmotic regulation. All of these impairments can limit a fish’s ability to provide appropriate oxygen to its cells, hence diminishing its physical activity and productivity.