bluuebunny/crossref_metadata_2025 huggingface dataset:
Personal, peaceful, progressive: Integration workers’ narratives of refugee settlement and the rural
Authors: Sætermo Turid , Kristensen Guro Korsnes
Published: December 2023

Settlement of refugees in rural areas in Norway is part of a national strategy to counter depopulation and thus links to ideas of revitalization and more promising futures for these areas. It also links up to an idea of smaller communities as ‘better at integrating’, as smaller communities both enable and necessitate more contact between the original population and newcomers. However, although some municipalities reap advantages of the dispersed settlement policy and succeed in retaining settled refugees, other municipalities ‘fail’. This article explores how the integration of refugees in rural communities is interpreted by public integration workers in two rural–coastal municipalities where the outcomes differ significantly. Drawing on 15 qualitative interviews, we discuss how integration workers make sense of local integration efforts, and how notions of the rural are (re)produced through their integration narratives. The analysis finds that the integration narratives draw on and reproduce both distinct and overlapping imaginaries of rural areas. We identify two main imaginaries: the rural as future‐oriented and dynamic, and the rural as close‐knit and peaceful.
Texture-Dependent Thermal Properties of Sandstone Rocks Examined by Scanning Electron Microscopy for Thermal Energy Storage Applications
Authors: Vivas Cesar , Hu Zeming , Salehi Saeed
Published: December 2023

Sedimentary rocks are widely used as geological reservoirs and as host rocks for geothermal energy systems. The thermal properties of sedimentary rocks, such as thermal conductivity, thermal diffusivity, and volumetric specific heat, play a critical role in their suitability for these applications. This study examined the thermal properties of 30 different sandstone rock samples using scanning electron microscopy (SEM) analysis. The SEM images of rock samples with different thermal properties were compared to analyze how textural properties influence thermal properties. Our results suggest that the thermal properties of sedimentary rocks are highly dependent on their texture. Specifically, we found that rocks with a higher degree of roughness, tend to exhibit lower thermal conductivity and thermal diffusivity. The presence of pores and cracks impacted the thermal properties of the sandstone rocks examined. The average surface roughness extracted from images showed a strong negative correlation with thermal conductivity and diffusivity (−0.59 and −0.6, respectively) obtained experimentally, while pore, cracks, and voids area have a less apparent negative correlation (−0.18 and −0.17) likely due to their complex effect on heat transfer. The size, shape, and distribution of voids affect heat transfer, with interconnected voids providing networks for heat flow, and smaller voids trapping heat more effectively. The texture of sedimentary rocks plays a critical role in determining their thermal properties. This knowledge can be used to optimize the understanding of the potential of sandstone reservoirs in applications, such as geothermal energy or thermal energy storage.
Fuel Failure Mechanisms and Fuel Failures
Authors: Onder E. Nihan
Published: December 2023

The term “fuel element failure” is used to indicate that the cladding is breached and the activity in the coolant can be detectable. The most important indicators to be measured for failed fuel elements include: i) iodine-131 in the primary coolant, ii) the sum of the activity of iodine isotopes, iii) radioactive noble gases, iv) uranium concentration in the primary coolant.
Fuel Safety and Acceptance Criteria
Authors: Onder E. Nihan
Published: December 2023

Fuel operational or design limits are established to avoid fuel failures during normal operation, and to mitigate the consequences of accidents. Following a severe accident, some radiological releases are expected and in most countries dose rate limits are defined for a possible off-site radiological release. Consequently, fuel safety criteria which relate to fuel damage are specified to ensure that these limits are not exceeded.
Mitochondrial metabolic flexibility is critical for CD8
+
T cell antitumor immunity
Authors: Chen Chao , Zheng Hong , Horwitz Edwin M. , Ando Satomi , Araki Koichi , Zhao Peng , Li Zhiguo , Ford Mandy L. , Ahmed Rafi , Qu Cheng-Kui
Published: December 2023

Mitochondria use different substrates for energy production and intermediatory metabolism according to the availability of nutrients and oxygen levels. The role of mitochondrial metabolic flexibility for CD8
+
T cell immune response is poorly understood. Here, we report that the deletion or pharmacological inhibition of protein tyrosine phosphatase, mitochondrial 1 (PTPMT1) significantly decreased CD8
+
effector T cell development and clonal expansion. In addition,
PTPMT1
deletion impaired stem-like CD8
+
T cell maintenance and accelerated CD8
+
T cell exhaustion/dysfunction, leading to aggravated tumor growth. Mechanistically, the loss of PTPMT1 critically altered mitochondrial fuel selection—the utilization of pyruvate, a major mitochondrial substrate derived from glucose—was inhibited, whereas fatty acid utilization was enhanced. Persistent mitochondrial substrate shift and metabolic inflexibility induced oxidative stress, DNA damage, and apoptosis in
PTPMT1
knockout cells. Collectively, this study reveals an important role of PTPMT1 in facilitating mitochondrial utilization of carbohydrates and that mitochondrial flexibility in energy source selection is critical for CD8
+
T cell antitumor immunity.
Probing surface Earth reactive silica cycling using stable Si isotopes: Mass balance, fluxes, and deep time implications
Authors: Rahman Shaily , Trower Elizabeth J.
Published: December 2023

Geological reservoir δ
30
Si values have increasingly been applied as paleoclimate and paleoproductivity proxies. Many of these applications rely on the assumption that the surface Earth Si isotope budget is in mass balance with bulk silicate Earth, such that trends in δ
30
Si over time can be attributed to changes in flux to or from key silica reservoirs. We compiled δ
30
Si data from modern reservoirs representing the major sources and sinks of surface Earth reactive silica, to which we applied an inverse model to test assumptions about mass balance. We found that δ
30
Si values of reverse weathering products must closely match those of diatoms, conflicting with previous assumptions. Model results also revealed that of the 19 to 21 teramoles per year Si released during silicate mineral weathering, ~10 to 18 teramoles per year is stored in terrestrial silica sinks, consistent with assumptions of incongruent weathering reactions. Our results demonstrated that the modern silica cycle summary is in isotopic mass balance.
Structural basis for flagellin-induced NAIP5 activation
Authors: Paidimuddala Bhaskar , Cao Jianhao , Zhang Liman
Published: December 2023

The NAIP (NLR family apoptosis inhibitory protein)/NLRC4 (NLR family CARD containing protein 4) inflammasome senses Gram-negative bacterial ligand. In the ligand-bound state, the winged helix domain of NAIP forms a steric clash with NLRC4 to open it up. However, how ligand binding activates NAIP is less clear. Here, we investigated the dynamics of the ligand-binding region of inactive NAIP5 and solved the cryo-EM structure of NAIP5 in complex with its specific ligand, FliC from flagellin, at 2.9-Å resolution. The structure revealed a “trap and lock” mechanism in FliC recognition, whereby FliC-D0
C
is first trapped by the hydrophobic pocket of NAIP5, then locked in the binding site by ID (insertion domain) and C-terminal tail of NAIP5. The FliC-D0
N
domain further inserts into ID to stabilize the complex. According to this mechanism, FliC triggers the conformational change of NAIP5 by bringing multiple flexible domains together.
DECTIN-1: A modifier protein in CTLA-4 haploinsufficiency
Authors: Turnbull Cynthia , Bones Josiah , Stanley Maurice , Medhavy Arti , Wang Hao , Lorenzo Ayla May D. , Cappello Jean , Shanmuganandam Somasundhari , Pandey Abhimanu , Seneviratne Sandali , Brown Grant J , Meng Xiangpeng , Fulcher David , Burgio Gaetan , Man Si Ming , de Lucas Collantes Carmen , Gasior Mercedes , López Granados Eduardo , Martin Pilar , Jiang Simon H. , Cook Matthew C. , Ellyard Julia I. , Athanasopoulos Vicki , Corry Ben , Canete Pablo F. , Vinuesa Carola G.
Published: December 2023

Autosomal dominant loss-of-function (LoF) variants in cytotoxic T-lymphocyte associated protein 4 (
CTLA4
) cause immune dysregulation with autoimmunity, immunodeficiency and lymphoproliferation (IDAIL). Incomplete penetrance and variable expressivity are characteristic of IDAIL caused by CTLA-4 haploinsufficiency (CTLA-4h), pointing to a role for genetic modifiers. Here, we describe an IDAIL proband carrying a maternally inherited pathogenic
CTLA4
variant and a paternally inherited rare LoF missense variant in
CLEC7A,
which encodes for the β-glucan pattern recognition receptor DECTIN-1. The
CLEC7A
variant led to a loss of DECTIN-1 dimerization and surface expression. Notably, DECTIN-1 stimulation promoted human and mouse regulatory T cell (T
reg
) differentiation from naïve αβ and γδ T cells, even in the absence of transforming growth factor–β. Consistent with DECTIN-1’s T
reg
-boosting ability, partial DECTIN-1 deficiency exacerbated the T
reg
defect conferred by CTL4-4h. DECTIN-1/
CLEC7A
emerges as a modifier gene in CTLA-4h, increasing expressivity of
CTLA4
variants and acting in functional epistasis with CTLA-4 to maintain immune homeostasis and tolerance.
USP2 inhibition prevents infection with ACE2-dependent coronaviruses in vitro and is protective against SARS-CoV-2 in mice
Authors: Dang Fabin , Bai Lei , Dong Jiazhen , Hu Xiaoping , Wang Jingchao , Paulo Joao A. , Xiong Yan , Liang Xiaowei , Sun Yishuang , Chen Yuncai , Guo Ming , Wang Xin , Huang Zhixiang , Inuzuka Hiroyuki , Chen Li , Chu Chen , Liu Jianping , Zhang Tao , Rezaeian Abdol-Hossein , Liu Jing , Kaniskan Husnu Ümit , Zhong Bo , Zhang Jinfang , Letko Michael , Jin Jian , Lan Ke , Wei Wenyi
Published: December 2023

Targeting angiotensin-converting enzyme 2 (ACE2) represents a promising and effective approach to combat not only the COVID-19 pandemic but also potential future pandemics arising from coronaviruses that depend on ACE2 for infection. Here, we report ubiquitin specific peptidase 2 (USP2) as a host-directed antiviral target; we further describe the development of MS102, an orally available USP2 inhibitor with viable antiviral activity against ACE2-dependent coronaviruses. Mechanistically, USP2 serves as a physiological deubiquitinase of ACE2, and targeted inhibition with specific small-molecule inhibitor ML364 leads to a marked and reversible reduction in ACE2 protein abundance, thereby blocking various ACE2-dependent coronaviruses tested. Using human ACE2 transgenic mouse models, we further demonstrate that ML364 efficiently controls disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as evidenced by reduced viral loads and ameliorated lung inflammation. Furthermore, we improved the in vivo performance of ML364 in terms of both pharmacokinetics and antiviral activity. The resulting lead compound, MS102, holds promise as an oral therapeutic option for treating infections with coronaviruses that are reliant on ACE2.
Genomic instability analysis in DNA from Papanicolaou test provides proof-of-principle early diagnosis of high-grade serous ovarian cancer
Authors: Paracchini Lara , Mannarino Laura , Romualdi Chiara , Zadro Riccardo , Beltrame Luca , Fuso Nerini Ilaria , Zola Paolo , Laudani Maria E. , Pagano Eva , Giordano Livia , Fruscio Robert , Landoni Fabio , Franceschi Silvia , Dalessandro Maria L. , Canzonieri Vincenzo , Bocciolone Luca , Lorusso Domenica , Bosetti Cristina , Raspagliesi Francesco , Garassino Isabella M. G. ,   the TOWARDS group, D’Incalci Maurizio , Marchini Sergio
Published: December 2023

Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic
TP53
mutations, this assay could detect HGSOC presence up to 9 years before diagnosis. This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.
Comparison of three rapid diagnostic tests for bloodstream infections using Benefit-risk Evaluation Framework (BED-FRAME)
Authors: Smith Richard D. , Zhan Min , Zhang Shanshan , Leekha Surbhi , Harris Anthony , Doi Yohei , Evans Scott , Kristie Johnson J. , Ernst Robert K.
Published: December 2023

Rapid diagnostic tests (RDTs) for bloodstream infections have the potential to reduce time to appropriate antimicrobial therapy and improve patient outcomes. Previously, an in-house, lipid-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) method, Fast Lipid Analysis Technique (FLAT MS), has shown promise as a rapid pathogen identification method. In this study, FLAT MS for direct from blood culture identification was evaluated and compared to FDA-cleared identification methods using the Benefit-risk Evaluation Framework (BED-FRAME) analysis. FLAT MS was evaluated and compared to Bruker Sepsityper and bioMérieux BioFire FilmArray BCID2 using results from a previous study. For this study, 301 positive blood cultures were collected from the University of Maryland Medical Center. The RDTs were compared by their sensitivities, time-to-results, hands-on time, and BED-FRAME analysis. The overall sensitivity of all platforms compared to culture results from monomicrobial-positive blood cultures was 88.3%. However, the three RDTs differed in their accuracy for identifying Gram-positive bacteria, Gram-negative bacteria, and yeast. Time-to-results for FLAT MS, Sepsityper, and BioFire BCID2 were all approximately one hour. Hands-on times for FLAT MS, Sepsityper, and BioFire BCID2 were 10 (±1.3), 40 (±2.8), and 5 (±0.25) minutes, respectively. BED-FRAME demonstrated that each RDT had utility at different pathogen prevalence and relative importance. BED-FRAME is a useful tool that can used to determine which RDT is best for a healthcare center.
Coexisting bilateral ciliochoroidal effusion syndrome and an isolated cytotoxic corpus callosum lesion in dengue fever
Authors: Raj Anuradha , Kaur Harmeet , Mangla Lavi , Madaan Sushant
Published: December 2023

Dengue fever is a major health concern in India. There are various reports in the literature regarding the ocular manifestations of this febrile illness. We are reporting a rare case of a woman in her late 30s who developed coexisting bilateral ciliochoroidal effusion syndrome with an isolated cytotoxic corpus callosum lesion associated with dengue febrile illness. To the best of our knowledge, this is the first case of its kind. It opens the avenues for neurological and radioimaging attention for such cases with bilateral ciliochoroidal effusion syndrome.
Early surgical repair of combined latissimus dorsi and teres major avulsion
Authors: Rademaker Eva , Beekhuizen Stefan Robin , Bos Cynthia , van der Zwaal Peer
Published: December 2023

A combined avulsion of both the latissimus dorsi muscle and teres major muscle is a rare occurrence and data focused on the treatment of this type of injury is limited to case studies and series. This case report presents the outcomes of early surgical repair for avulsions of the latissimus dorsi and teres major tendons in a high-demanding athlete. The patient underwent surgical repair using a single incision technique and endosteal button fixation of the avulsed tendons. This procedure was performed within 4 weeks of the initial injury, followed by a progressive mobilisation regimen in the postoperative phase. After a period of 3 months, the patient successfully participated in his first international competition. This report describes the effectiveness of early surgical repair after latissimus dorsi and teres major tendon avulsion. The single incision technique and the use of endosteal buttons for tendon fixation yielded excellent results for a professional judoka.
Iatrogenic enterovesical fistula secondary to a permanent urinary catheter
Authors: Dagnesses Fonseca Javier Oscar , Teja García Gabriel , Luengo Batres Paloma , Calvo Espino Pablo
Published: December 2023

An enterovesical fistula is a rare entity resulting from inflammatory, neoplastic and iatrogenic processes. It can manifest clinically as pneumaturia and recurrent urinary tract infections. Its diagnosis is supported by imaging examinations and its treatment is primarily surgical.
Electroacupuncture for mild-to-moderate dry eye: study protocol for a multicentre, randomised, single-blind, sham-controlled trial
Authors: Lu Yun-Qiong , Yang Guang , Li Mei-Yan , Hong Jue , Yang Yan-Ting , Wang Xue-Jun , Kong Xie-He , Zhao Yue , Ma Zhao , Huang Xin-Yun , Zou Yue-Lan , Zhou Xing-Tao , Ma Xiao-Peng
Published: December 2023

Introduction

Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE.

Methods and analysis

This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale.

Ethics and dissemination

The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021–119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014).

Trial registration number

NCT05552820.
Trends in the treatment of fibromyalgia in South Korea between 2011 and 2018: a retrospective analysis of cross-sectional health insurance data
Authors: Yu Jin-Sil , Kim Eun-San , Park Kyoung Sun , Lee Yoon Jae , Park Yeon Cheol , Nam Dongwoo , Kim Eun-Jung , Ha In-Hyuk
Published: December 2023

Objectives

Fibromyalgia treatment trends vary globally; however, the trend in South Korea has not been investigated yet. This study aimed to analyse the fibromyalgia treatment trends in South Korea.

Design

Retrospective, observational study using serial cross-sectional data.

Setting

The National Patient Samples of the Korean Health Insurance Review & Assessment Service from 2011 to 2018 were used.

Participants

A total of 31 059 patients with fibromyalgia were included in this study. The basic characteristics of the patients were stratified by sex, age and comorbidity. A patient was considered to have a condition if it was recorded as a principal diagnosis at least once in a year.

Primary and secondary outcome measures

Trends in the types of medical visits and prescribed treatments were investigated and the values are presented as rates per 100 patients. The types of pharmacological treatment were presented according to the existing clinical guidelines. Additionally, combination prescription trends and associated characteristics were investigated.

Results

Of the patients, 66.2% were female. Visits to internal medicine departments showed the most significant increase (2011: 11.34; 2018: 21.99; p<0.001). Non-pharmacological treatment rates declined (physical therapy 2011: 18.11; 2018: 13.69; p<0.001, acupuncture 2011: 52.03; 2018: 30.83; p<0.001). Prescription rates increased for analgesics, relaxants, antiepileptics and antidepressants. Non-steroidal anti-inflammatory drug prescriptions had the highest increase (2011: 27.65; 2018: 40.02; p<0.001). Serotonin–norepinephrine reuptake inhibitor prescriptions showed significant growth (2011: 2.4; 2018: 8.05; p<0.001). Prescription durations were generally longer for women (p<0.001), with higher rate increases in this group. Combinations of ≥3 medication classes increased (2011: 8.2; 2018: 9.64; p=0.041). Women were more likely to receive combination prescriptions (crude OR 1.47 (95% CI 1.29 to 1.68), adjusted 1.18 (95% CI 1.03 to 1.36)).

Conclusions

Our findings provide basic reference data for the development and application of national guidelines for fibromyalgia.
Association between dietary knowledge and muscle mass in Chinese older adults: a cross-sectional and longitudinal study
Authors: Liu Qiaoling , Wang Luonan , Ma Yuge , Geng Yunjie
Published: December 2023

Objectives

This study aims to explore the possible association between dietary knowledge and muscle mass in a Chinese population aged 60 years and above.

Design

Cross-sectional and longitudinal studies.

Setting

Data from the 2006 and 2011 China Health and Nutrition Survey (CHNS) were used for this study.

Participants

A total of 1487 Chinese participants (44.38% males) aged 60 and above in the 2006 survey were included in the cross-sectional study. From the same study population, a total of 1023 participants (46.82% males) with normal muscle mass on the interview date of 2006 were included in the longitudinal study.

Outcome measures

Dietary knowledge was accessed by a validated CHNS questionnaire. Appendicular skeletal muscle mass was calculated using a validated anthropometric equation derived from a representative Chinese population. Based on the 2021 Chinese consensus on sarcopenia, the appendicular skeletal muscle mass was categorised as ‘normal’ or ‘low’ using sex-specific cut-off values.

Results

The prevalence of low muscle mass in the study population was 31.20%, with a higher prevalence in females (34.22%). People with low muscle mass have a significantly lower dietary knowledge score (mean difference: −1.74, 95% CI −2.20 to −1.29). In the cross-sectional analysis, one score higher in dietary knowledge score was associated with a 4% lower odds of low muscle mass (OR=0.96, 95% CI 0.93 to 0.99). Compared with people in the lowest quartile of dietary knowledge, people in the highest quartile have a 44% lower odds of low muscle mass (OR=0.56, 95% CI 0.35 to 0.91). In the longitudinal analysis, no significant association was found between dietary knowledge and low muscle mass, yet the upper 95% CI was close to one (HR=0.97, 95% CI 0.93 to 1.01).

Conclusions

Sufficient dietary knowledge may play a protective role in maintaining normal muscle mass in Chinese adults aged 60 or above.
Understanding the patterns and health impact of indoor air pollutant exposures in Bradford, UK: a study protocol
Authors: Ikeda Erika , Hamilton Jacqueline , Wood Chantelle , Chatzidiakou Lia , Warburton Thomas , Ruangkanit Athina , Shao Yunqi , Genes Denisa , Waiblinger Dagmar , Yang Tiffany C , Giorio Chiara , McFiggans Gordon , O'Meara Simon P , Edwards Pete , Bates Elizabeth , Shaw David R , Jones Roderic L , Carslaw Nicola , McEachan Rosemary
Published: December 2023

Introduction

Relative to outdoor air pollution, there is little evidence examining the composition and concentrations of indoor air pollution and its associated health impacts. The INGENIOUS project aims to provide the comprehensive understanding of indoor air pollution in UK homes.

Methods and analysis

‘Real Home Assessment’ is a cross-sectional, multimethod study within INGENIOUS. This study monitors indoor air pollutants over 2 weeks using low-cost sensors placed in three rooms in 300 Born in Bradford (BiB) households. Building audits are completed by researchers, and participants are asked to complete a home survey and a health and behaviour questionnaire, in addition to recording household activities and health symptoms on at least 1 weekday and 1 weekend day. A subsample of 150 households will receive more intensive measurements of volatile organic compound and particulate matter for 3 days. Qualitative interviews conducted with 30 participants will identify key barriers and enablers of effective ventilation practices. Outdoor air pollution is measured in 14 locations across Bradford to explore relationships between indoor and outdoor air quality. Data will be analysed to explore total concentrations of indoor air pollutants, how these vary with building characteristics, and whether they are related to health symptoms. Interviews will be analysed through content and thematic analysis.

Ethics and dissemination

Ethical approval has been obtained from the NHS Health Research Authority Yorkshire and the Humber (Bradford Leeds) Research Ethics Committee (22/YH/0288). We will disseminate findings using our websites, social media, publications and conferences. Data will be open access through the BiB, the Open Science Framework and the UK Data Service.
Machine-learning-based image analysis algorithms improve interpathologist concordance when scoring PD-L1 expression in non-small-cell lung cancer
Authors: Haragan Alexander , Parashar Piya , Bury Danielle , Cross Gregory , Gosney John R
Published: December 2023

Programmed death ligand 1 (PD-L1) expression on tumour cells is the only predictive biomarker of response to immuno-modulatory therapy for patients with non-small-cell lung cancer (NSCLC). Accuracy of this biomarker is hampered by its challenging interpretation. Here we explore if the use of machine-learning derived image analysis tools can improve interpathologist concordance of assessing PD-L1 expression in NSCLC.

Five pathologists who routinely score PD-L1 at a major regional referral hospital for thoracic surgery participated. 13 NSCLC small diagnostic biopsies were stained for PD-L1 (SP263 clone) and digitally scanned. Each pathologist independently scored each case with and without the Roche uPath PD-L1 (SP263) image analysis NSCLC algorithm with a wash-out interim period of 6 weeks.

A consistent improvement in interpathologist concordance was seen when using the image analysis tool compared with scoring without: (Fleiss’ kappa 0.886 vs 0.613 (p<0.0001) and intraclass coefficient correlation 0.954 vs 0.837 (p<0.001)). Five cases (38%) were classified into clinically relevant different categories (negative/weak/strong) by multiple pathologists when not using the image analysis algorithm, whereas only two cases (15%) were classified differently when using the image analysis algorithm.

The use of the image analysis algorithm improved the concordance of assessing PD-L1 expression between pathologists. Critically, there was a marked improvement in the placement of cases into more consistent clinical groupings. This small study is evidence that the use of image analysis tools may improve consistency in assessing tumours for PD-L1 expression and may therefore result in more consistent prediction to targeted treatment options.
Assessment and personalised advice for fatigue in systemic lupus erythematosus using an innovative digital tool: the Lupus Expert system for the Assessment of Fatigue (LEAF) study
Authors: Kawka Lou , Sarmiento-Monroy Juan-Camilo , Mertz Philippe , Pijnenburg Luc , Rinagel Marina , Ugarte-Gil Manuel Francisco , Geneton Sophie , Blaess Julien , Piga Matteo , Arnaud Laurent
Published: December 2023

Background

Fatigue is reported as the most prevalent symptom by patients with systemic lupus erythematosus (SLE). Fatigue management is complex due to its multifactorial nature. The aim of the study was to assess the usefulness of an innovative digital tool to manage fatigue in SLE, in a completely automated manner.

Methods

The «Lupus Expert System for Assessment of Fatigue» (LEAF) is free digital tool which measures the intensity and characteristics of fatigue and assesses disease activity, pain, insomnia, anxiety, depression, stress, fibromyalgia and physical activity using validated patient-reported instruments. Then, LEAF automatically provides personalised feedback and recommendations to cope with fatigue.

Results

Between May and November 2022, 1250 participants with SLE were included (95.2% women, median age 43yo (IQR: 34–51)). Significant fatigue (Functional Assessment of Chronic Illness Therapy-Fatigue <34) was reported by 78.9% of patients. In univariate analysis, SLE participants with fatigue were more likely to be women (p=0.01), perceived their disease as more active (p<0.0001), had higher levels of pain (p<0.0001), anxiety (p<0.0001), depression (p<0.0001), insomnia (p<0.0001), stress (p<0.0001) and were more likely to screen for fibromyalgia (p<0.0001), compared with patients without significant fatigue. In multivariable analysis, parameters independently associated with fatigue were insomnia (p=0.0003), pain (p=0.002), fibromyalgia (p=0.008), self-reported active SLE (p=0.02) and stress (p=0.045). 93.2% of the participants found LEAF helpful and 92.3% would recommend it to another patient with SLE.

Conclusion

Fatigue is commonly severe in SLE, and associated with insomnia, pain, fibromyalgia and active disease according to patients’ perspective. Our study shows the usefulness of an automated digital tool to manage fatigue in SLE.
Time trends in the burden of autoimmune diseases across the BRICS: an age–period–cohort analysis for the GBD 2019
Authors: Zhang Fenghao , Cui Yiran , Gao Xiao
Published: December 2023

Background

This study aims to evaluate the long-term trend of prevalence and DALY (disability-adjusted life-year) rate on the age, period and cohort (APC) of the BRICS (Brazil, Russia, India, China and South Africa) country for autoimmune diseases (rheumatoid arthritis (RA), inflammatory bowel disease (IBD), multiple sclerosis (MS) and psoriasis).

Methods

The data are sourced from the Global Burden of Disease Study 2019, and it uses the Joinpoint regression model to estimate the time trends of autoimmune diseases from 1990 to 2019. Additionally, it employs the Age-Period-Cohort (APC) model to estimate the age, period, and cohort effects from 1990 to 2019.

Results

For 1990 to 2019, the ASPR (age-standardised prevalence rate) of IBD increased significantly for China and South Africa, and decreased significantly for Brazil, India, Russian. The Russian ASPR of MS demonstrated a significantly decreasing trend (average annual percent change=−0.5%, 95% CI −0.6 to −0.5), with the most increased occurring in Brazil at 2009–2014. The cohort effect on DALY rates for Psoriasis displayed an ongoing decreasing trend from the 1929–1933 birth cohort to the 1999–2003 birth cohort. Specifically, the five countries relative risk values (RRs) of DALYs due to RA increased significantly by 7.98, 16.07, 5.98, 3.19, 9.13 times, from 20 to 24 age group to 65 to 69 age group.

Conclusions

The population of the BRICS countries accounts for more than 40% of the global population. And we found that the age effect of various autoimmune diseases is heavily influenced by population ageing.
HCF4−n(SO3)n (n=1–4): Designing new series of organic superacids
Authors: Tripathi Jitendra Kumar , Misra Neeraj , Srivastava Ambrish Kumar
Published: December 2023

Superacids are systems that exhibit higher acidity compared to extremely strong mineral acid, i.e. 100% pure sulphuric acid (H2SO4). They can be designed by the protonation of appropriate superhalogen anions. Superhalogens possess higher electron affinity (EA) than halogens. Most recent examples include CF[Formula: see text], which behave as superhalogens for [Formula: see text]. In this work, we studied the protonation of CF[Formula: see text] using density functional theory calculations at the B3LYP/6-311[Formula: see text] level. The Gibbs’ free energies of deprotonation ([Formula: see text]) values of the resulting protonated complexes, HCF[Formula: see text] for [Formula: see text]–4; are either lower or nearly equivalent to that of H2SO4 ([Formula: see text][Formula: see text]kcal/mol). This suggests that all these protonated complexes exhibit superacidic behavior. Notably, the HC[Formula: see text] compound undergoes significant structural relaxation, leading to a remarkably less [Formula: see text] value. Our findings should enrich the literature with a new series of superacids and motivate further studies to explore novel organic superacids.
GAN-Place: Advancing Open Source Placers to Commercial-quality Using Generative Adversarial Networks and Transfer Learning
Authors: Lu Yi-Chen , Ren Haoxing , Hsiao Hao-Hsiang , Lim Sung Kyu
Published: December 2023

Recently, GPU-accelerated placers such as DREAMPlace and Xplace have demonstrated their superiority over traditional CPU-reliant placers by achieving orders of magnitude speed up in placement runtime. However, due to their limited focus in placement objectives (e.g., wirelength and density), the placement quality achieved by DREAMPlace or Xplace is not comparable to that of commercial tools. In this article, to bridge the gap between open source and commercial placers, we present a novel placement optimization framework named GAN-Place that employs generative adversarial learning to transfer the placement quality of the industry-leading commercial placer, Synopsys ICC2, to existing open source GPU-accelerated placers (DREAMPlace and Xplace). Without the knowledge of the underlying proprietary algorithms or constraints used by the commercial tools, our framework facilitates transfer learning to directly enhance the open source placers by optimizing the proposed differentiable loss that denotes the “similarity” between DREAMPlace- or Xplace-generated placements and those in commercial databases. Experimental results on seven industrial designs not only show that our GAN-Place immediately improves the Power, Performance, and Area metrics at the placement stage but also demonstrates that these improvements last firmly to the post-route stage, where we observe improvements by up to 8.3% in wirelength, 7.4% in power, and 37.6% in Total Negative Slack on a commercial CPU benchmark.
Complex Roles of PTPN11/SHP2 in Carcinogenesis and Prospect of Targeting SHP2 in Cancer Therapy
Authors: Scheiter Alexander , Lu Li-Chun , Gao Lilian H. , Feng Gen-Sheng
Published: December 2023

The nonreceptor tyrosine phosphatase SHP2 has been at the center of cell signaling research for three decades. SHP2 is required to fully activate the RTK/RAS/ERK signaling cascade, although the underlying mechanisms are not completely understood. PTPN11, which encodes SHP2, is the first identified proto-oncogene that encodes a tyrosine phosphatase, with dominantly activating mutations detected in leukemias and solid tumors. However, SHP2 has pro- and antioncogenic effects, and the most recent data reveal opposite activities of SHP2 in tumor cells and microenvironment cells. Allosteric SHP2 inhibitors show promising antitumor effects and overcome resistance to inhibitors of RAS/ERK signaling in animal models. Many clinical trials with orally bioactive SHP2 inhibitors, alone or combined with other regimens, are ongoing for a variety of cancers worldwide, with therapeutic outcomes yet unknown. This review discusses the multifaceted functions of SHP2 in oncogenesis, preclinical studies, and clinical trials with SHP2 inhibitors in oncological treatment.
Deciphering the Warburg Effect: Metabolic Reprogramming, Epigenetic Remodeling, and Cell Dedifferentiation
Authors: Li Albert M. , Ye Jiangbin
Published: December 2023

A century ago, Otto Heinrich Warburg made a seminal discovery now known as the Warburg effect. This metabolic signature, prevalent across all cancer cells, is characterized by the prominent shift of glucose metabolism toward lactate production instead of oxidative respiration. Warburg's pioneering theory suggested that the induction of the Warburg effect instigates dedifferentiation and the process of tumorigenesis, illuminating a fundamental mechanism underlying cancer development. To celebrate the centennial anniversary of Warburg's monumental finding, it is an appropriate moment to reflect upon and commemorate his revolutionary contributions to the fields of metabolism and cancer research. In this review, we explore the role of mitochondria in epigenetic regulation and the decisions governing cell fate from an evolutionary standpoint. Moreover, we summarize metabolic and genetic factors that trigger the Warburg effect, underscoring the therapeutic potential of mitochondrial uncoupling as a strategy to counter this metabolic aberration. Our goal is to elucidate the means to induce tumor differentiation through metabolic therapy, thereby laying a foundation toward the cure for cancer.
The Mobility of Drops, Pearls, and Marbles
Authors: Quéré David
Published: December 2023

At the scale of drops, water either sticks to inclined solids or moves, yet slowly—without the mobility we expect of a liquid of low viscosity. We first recall that the contact line that bounds a drop is responsible for these special adhesion and enhanced friction properties. Then, we discuss how inducing nonwetting states (pearls and marbles) minimizes the role of this line, restores mobility, and even boosts the liquid when it is viscous.
Economic Stress and Occupational Health
Authors: Sinclair Robert R. , Graham Baylor A. , Probst Tahira M.
Published: December 2023

Economic sources of stress are some of the most pervasive and significant in adults’ working lives. However, while the link between economic stress and health is well established, some forms of economic stress have received disproportionately less attention than they warrant in organizational psychology and organizational behavior scholarship. In this review, we identify five important domains of economic stress: financial stress, financial deprivation, unemployment, underemployment, and job insecurity. We review each area of literature, focusing on its antecedents, theoretical mechanisms, and consequences. We then highlight an emerging body of research that studies economic stress as a multilevel phenomenon and present a framework for economic stress interventions that discusses primary, secondary, and tertiary interventions at the individual, organizational, and community levels. We conclude by identifying several important directions for future economic stress research.
Effects of Traditional and Novel Cooking Processes on the Nutritional and Bioactive Profile of Brassica oleracea (Kale)
Authors: Khalid Waseem , Ikram Ali , Nadeem Muhammad Tahir , Arshad Muhammad Sajid , Rodrigues Sarah de Oliveira , Pagnossa Jorge Pamplona , Al-Farga Ammar , Chamba Moses Vernonxious Madalitso , Batiha Gaber El-Saber , Koraqi Hyrije
Published: December 2023

The present study investigates the impact of traditional and novel cooking techniques on the nutritional and bioactive profile of Brassica oleracea, commonly known as kale. As a member of the Brassica family, kale is well known for its high nutritional value and possible health benefits. However, it is crucial to remember that the cooking techniques can significantly impact the nutritional profile of kale. Various cooking methods were applied to kale samples through controlled experiments. Traditional techniques like boiling and steaming were compared with innovative approaches such as microwave cooking and vacuum cooking. Soluble solids, which include sugars and other compounds, were used as indicators of nutritional change. Additionally, the levels of vital bioactive components, such as vitamins, antioxidants, and phytochemicals, were analyzed to assess the overall impact of cooking methods. Preliminary findings suggest that the choice of cooking method plays a pivotal role in determining the extent of nutritional and bioactive alterations in kale. Traditional methods, such as boiling, exhibited substantial losses of soluble solids and certain heat-sensitive nutrients. In contrast, novel methods like vacuum cooking displayed better preservation of soluble solids and bioactive compounds. The study sheds light on the complex relationship between cooking techniques and the nutritional integrity of kale. By exploring various methods, this review paper contributes to understanding how culinary practices can be optimized to enhance the retention of vital nutrients and beneficial bioactive components in kale. These findings hold practical implications for individuals seeking to maximize the health benefits of kale consumption while enjoying its culinary versatility.
Knowledge Is (Still) Key: Awareness to Shape Trends in Telemedicine Use during the Pandemic Based on Management Perceptions and Implementation Systems
Authors: Hawa Nada I. , Soesilo Tri E. B. , Nuraeni Nuraeni
Published: December 2023

Objectives. The digital revolution has brought rapid developments to the health sector. People were taking advantage of telemedicine technology during the COVID-19 pandemic. Telemedicine is highly recommended during a pandemic because it will reduce the transmission rate of viruses, and it is considered adequate and low-cost. However, a fundamental challenge still occurs; most people need to be used to telemedicine technology. Presumably, inadequate education and lack of experience regarding the use of telemedicine are obstacles for society in utilizing telemedicine. Methods. This study is aimed at determining the factors that influence the use of telemedicine. It focused on variables such as data confidentiality, administration, and knowledge to measure potential factors that pushed people to utilize telemedicine. We used a quantitative approach, using multivariate analysis, namely, simple linear regression. Most of our respondents are people aged 18-30 years young. Results. All respondents stated that administration factors in the implementation of telemedicine were good. Through the Chi-square test, the data safety factor has no effect (

p

value =0.090 or >0.05) on telemedicine implementation, while the knowledge factor has a significant effect on telemedicine implementation with a

p

value =0.043 (<0.005). The multivariate analysis explained that the knowledge variable influenced telemedicine use with a

p

value =0.033 (<0.05), meaning it contributed 1.624 times to telemedicine. Conclusion. This study discusses the factors that influence the use of telemedicine. The study’s results explain that the knowledge variable is the most significant factor influencing telemedicine use. Knowledge is an intellectual property that everyone must have to capitalize on with telemedicine. A lack of knowledge will become an information gap and a barrier for someone to reach new tools/technologies.
Sorption Behavior of Radionuclides on Engineered and Natural Barriers and Prediction of Sorption Distribution Coefficients Using Support Vector Regression
Authors: Lim Youngsu , Oh Gi-Taek , Kim Bolam , Kim Jinseob , Park Juhui , Lee Seongju , Choi Seho , Jang Jiseon , Kang Myunggoo , Ha Jaechul , Cho Chun-Hyung , Lee Min-Woo , Lee Dae Sung
Published: December 2023

A low- and intermediate-level radioactive waste repository contains various types of radionuclides and organic complexing agents. Their chemical interaction within the repository can lead to the formation of radionuclide-ligand complexes, influencing the limited retention behaviors of radionuclides. This study focuses on the sorption behavior of radionuclides on both engineered (concrete) and natural barriers (sedimentary rock and granite), as well as the prediction of sorption distribution coefficients (Kd) using support vector regression. Batch studies were conducted to determine the

K

d

values for three radionuclides (99Tc, 137Cs, and 238U) under different conditions, including pH, temperature, and the presence of organic ligands (such as ethylenediaminetetraacetic acid, nitrilotriacetic acid, and isosaccharinic acid). The

K

d

values for 238U exhibited a sharp decrease with increasing concentrations of organic ligands. In contrast, the

K

d

values for 99Tc showed only a slight reduction at higher organic ligand concentrations. Meanwhile, the

K

d

values for 137Cs remained relatively unchanged, regardless of the type and initial concentration of organic ligands. This suggests a high level of retention for 137Cs in the rock samples. The support vector regression model with a radial basis kernel function proved effective in predicting the

K

d

values under different experimental conditions. This enhancement in predicting accuracy contributes valuable insights into understanding the sorption processes involved in radionuclide behavior. Overall, this study advances our knowledge of radionuclide behavior on both engineered and natural barriers while providing a reliable prediction tool for estimating sorption distribution coefficients.
High Transmission Rates of Early Omicron Subvariant BA.2 in Bangkok, Thailand
Authors: Petcharat Sininat , Supataragul Ananporn , Hirunpatrawong Piyapha , Torvorapanit Pattama , Klungthong Chonticha , Chinnawirotpisan Piyawan , Ninwattana Sasiprapa , Thippamom Nattakarn , Paitoonpong Leilani , Suwanpimolkul Gompol , Jantarabenjakul Watsamon , Buathong Rome , Joonlasak Khajohn , Manasatienkij Wudtichai , Rattanatumhi Khwankamon , Chantasrisawad Napaporn , Chumpa Nuntana , Cotrone Thomas S. , Fernandez Stefan , Sriswasdi Sira , Wacharapluesadee Supaporn , Putcharoen Opass
Published: December 2023

The emergence of Omicron as the fifth variant of concern within the SARS-CoV-2 pandemic in late 2021, characterized by its rapid transmission and distinct spike gene mutations, underscored the pressing need for cost-effective and efficient methods to detect viral variants, especially given their evolving nature. This study sought to address this need by assessing the effectiveness of two SARS-CoV-2 variant classification platforms based on RT-PCR and mass spectrometry. The primary aim was to differentiate between Delta, Omicron BA.1, and Omicron BA.2 variants using 618 COVID-19-positive samples collected from Bangkok patients between November 2011 and March 2022. The analysis revealed that both BA.1 and BA.2 variants exhibited significantly higher transmission rates, up to 2-3 times, when compared to the Delta variant. This research presents a cost-efficient approach to virus surveillance, enabling a quantitative evaluation of variant-specific public health implications, crucial for informing and adapting public health strategies.