bluuebunny/crossref_metadata_2025 huggingface dataset:
Challenges and opportunities of growth centres in Bangladesh: rural development perspective
Authors: Arif Kazi Mostafa , Islam Sayed Rafiqul , Islam Ariful
Published: January 2024

Bangladesh is predominantly an agro-based economy where the rural economy is the linchpin of her development. Rural market i.e., rural growth centres serve as a hub of the rural economy. This study assessed the challenges and opportunities of growth centres in Bangladesh from the perspective of rural development. Twelve rural growth centres were randomly selected from the six Upazilas of Kushtia district of Bangladesh, and information was gathered from various stakeholders of those rural growth centres via a survey questionnaire. Focus Group Discussions (FGDs) with buyers and sellers as well as Key Informants Interviews (KIIs) with market committee members and chairman/members of the pertinent locality were held for this purpose. An indicator-based assessment technique developed to elucidate the connection between the growth centres and rural development. Furthermore, a Priority Index (PI) also utilized to rank the need for further investment in growth centres. The findings unveil that storage, loading/unloading facilities, and a women's toilet arrangement were essentially non-existent in the studied regions. Furthermore, the state of the connecting roadways from the farm to the market is unsuitable for market vendors. Finally, indicator-based assessment signifies that rural development elements are profoundly impacted by the growth centre. The policy implication is that, after acknowledging the real scenario of growth centres, we should rethink and rearrange investment policies from the standpoint of rural development.
The Future of Work in Diverse Economic Systems
Authors: Friel Daniel
Published: January 2024

This Element reviews varieties of capitalism (VoC) developed by Hall and Soskice and subsequent extensions to emerging markets. The author suggests that by reinvigorating existing ideal types and creating new ones through an analysis of its five variables in a variety of countries VoC can be used to evaluate the viability of economic reforms in each country, based on lessons from other countries belonging to their ideal type. It illustrates the utility of VoC in understanding how reforms will differ across countries by examining how the future of work is likely to differ across nations depending on the degree to which the five institutions explored in this approach promote the standardization of tasks. It analyzes how these institutions shape degrees of standardization in the United States, Germany, and Brazil, offering suggestions for reforms in each of them.
The Great Anglo-Russian Naval Alliance of the Eighteenth Century and Beyond
Authors: MacDougall Philip
Published: January 2024

Naval co-operation between Britain and Russia continued throughout the eighteenth century, with Britain providing huge assistance to the growth of Russia's navy, and Russia making an essential but often overlooked contribution to Britain's maritime power in the period. From 1698 when Tsar Peter the Great served briefly as a trainee shipwright at Deptford dockyard Russia recruited British, often Scottish, shipwrights, engineers, naval officers and naval surgeons who both helped build up the Russian navy and who were also key advisers to the Russian navy at sea. At the same time, naval stores from Russia, especially after Britain lost the American colonies, were vital for the maintenance of Britain's fleet. Moreover, as this book argues, Russian naval power was much more formidable than is often realised, with the Russian navy active alongside the British fleet in the North Sea and winning decisive battles against the Ottoman navy in the Mediterranean, including the battles of Çesme in 1770 and Navarino in 1827. Britain did well to have Russia as a naval ally rather than an enemy. This book provides a comprehensive overview of this important subject, at a time when Britain's relationship with Russia is of considerable concern.
Plants, Places, and Power
Authors: Stehle Maria
Published: January 2024

Examines portrayals of plants and landscapes in recent German novels and films, addressing the contemporary forms of racism, nationalism, and social and ecological injustice that they expose.
The Papacy and Ecclesiology of Honorius II (1124-1130)
Authors: Veneziani Enrico
Published: January 2024

A complete reappraisal of the papacy of Honorius II, highlighting the strategies to which this pontificate turned in order to govern ecclesiastical institutions and to deal with secular matters.
Britten's Donne, Hardy and Blake Songs
Authors: Sly Gordon Cameron
Published: January 2024

Presents a first analytical study that looks at the overarching designs of Benjamin Britten's John Donne, Thomas Hardy and William Blake solo song cycles.
Toward standardization, harmonization, and integration of social determinants of health data: A Texas Clinical and Translational Science Award institutions collaboration
Authors: Craven Catherine K. , Highfield Linda , Basit Mujeeb , Bernstam Elmer V. , Choi Byeong Yeob , Ferrer Robert L. , Gelfond Jonathan A. , Pruitt Sandi L. , Kannan Vaishnavi , Shireman Paula K. , Spratt Heidi , Morales Kayla J. Torres , Wang Chen-Pin , Wang Zhan , Zozus Meredith N. , Sankary Edward C. , Schmidt Susanne
Published: January 2024

Introduction:

The focus on social determinants of health (SDOH) and their impact on health outcomes is evident in U.S. federal actions by Centers for Medicare & Medicaid Services and Office of National Coordinator for Health Information Technology. The disproportionate impact of COVID-19 on minorities and communities of color heightened awareness of health inequities and the need for more robust SDOH data collection. Four Clinical and Translational Science Award (CTSA) hubs comprising the Texas Regional CTSA Consortium (TRCC) undertook an inventory to understand what contextual-level SDOH datasets are offered centrally and which individual-level SDOH are collected in structured fields in each electronic health record (EHR) system potentially for all patients.

Methods:

Hub teams identified American Community Survey (ACS) datasets available via their enterprise data warehouses for research. Each hub’s EHR analyst team identified structured fields available in their EHR for SDOH using a collection instrument based on a 2021 PCORnet survey and conducted an SDOH field completion rate analysis.

Results:

One hub offered ACS datasets centrally. All hubs collected eleven SDOH elements in structured EHR fields. Two collected Homeless and Veteran statuses. Completeness at four hubs was 80%–98%: Ethnicity, Race; < 10%: Education, Financial Strain, Food Insecurity, Housing Security/Stability, Interpersonal Violence, Social Isolation, Stress, Transportation.

Conclusion:

Completeness levels for SDOH data in EHR at TRCC hubs varied and were low for most measures. Multiple system-level discussions may be necessary to increase standardized SDOH EHR-based data collection and harmonization to drive effective value-based care, health disparities research, translational interventions, and evidence-based policy.
Navigating in the Dark
Authors: Godard Palluet Amélie , Gueguen Marie
Published: January 2024

This article introduces the snap hook methodology, a method used notably in astrochemistry as a way to indirectly validate and assess the accuracy of computational calculations in the absence of experimental or observational data. We argue that this methodology has tremendous potential for all computationally intensive scientific fields as a substitute for traditional verification and validation standards when those are not accessible and estimating the reliability of numerical predictions becomes a real difficulty. The goal of this article is to give to this method, which seems to be implicitly relied upon in many areas, a proper formulation, in order for philosophers of science to enter the debate and to highlight its undeniable potential in terms of interdisciplinary facilitation and knowledge transmission.
From the Heights of the Atlas: A Panorama of Traditional Poetry in Tamazight
Authors: Aoudjit Abdelkader
Published: January 2024

Traditional oral poetry in Takbaylit, Tachelhit, Central Moroccan Tamazight, and Tarafit dialects has been the subject of numerous studies ranging from ethnographic to linguistic. Rather than duplicate what is already widely available, the following brings together comments on a number of representative poems from across the Maghreb to give the reader an idea of the variety of types, styles, and themes of Tamazight poetic tradition. The selections, which are translated into English here for the first time, range from the moving devotional poem in Tachelhit “Like the Beads of a Rosary” to the beautiful love poem in Takbaylit “To Whom Should I Complain.” Among the poets whose works are included are Mririda n'Ait Attik (Tachelhit), Al Hadj Ammar ou al Hadj (Takbaylit), and Taougrat Oult Aissa (Central Moroccan Tamazigt).
Effect of different nutrients on blood glucose, inflammatory response and oxidative stress in gestational diabetes mellitus: a network meta-analysis
Authors: Yu Lingling , Zhu Yuan , Geng Lan , Xu Yueming , Zhao Mei
Published: January 2024

We searched PubMed, Web of Science, Embase, The Cochrane Library, China Biomedical Literature Database and other databases from inception to June 2023. The included studies were randomised controlled trials (RCT). The studies were screened by four authors, divided into two independent pairs. A total of eighteen studies were included, including 1362 patients, involving twelve intervention measures. The different nutrients had a significant effect on improving blood glucose, reducing inflammation levels and reducing oxidative stress compared with placebo (P < 0.05). Cumulative probability ranking showed that vitamin A + vitamin D + vitamin E ranked first in lowering fasting blood glucose (standardised mean difference (SMD) = 41.30, 95 % CI (2.07, 825.60)) and postprandial 2-h blood glucose (SMD = 15.19, 95 % CI (4.16, 55.53)). In terms of insulin resistance index, the first highest probability ranking is vitamin D (SMD = 5.12, 95 % CI (0.76, 34.54)). In terms of reducing the high-sensitivity C-reactive protein level, the first in probability ranking is VE (SMD = 2.58, 95 % CI (1.87,3.55)). The results of cumulative probability ranking showed that Mg + Zn + Ca + VD ranked first in reducing TNF-α (SMD = 1.90, 95% CI (0.40, 9.08)) and IL-6 (SMD = 1.83, 95 % CI (0.37, 9.12)). In terms of reducing malondialdehyde levels, the first ranked probability is VB1 (SMD = 4.99, 95 % CI (1.85, 13.46)). Cumulative probability ranking results showed that Ca + VD ranked first in reducing total antioxidant capacity (SMD = 0.66,95 % CI (0.38, 1.15)) and glutathione (SMD = 1.39, 95 % CI (0.43, 4.56)). In conclusion, nutritional interventions have significant effects on improving blood glucose, inflammatory levels and oxidative stress in patients with gestational diabetes. Due to the high uncertainty in the results and differences in the number and quality of studies included, the reliability of the conclusions still needs to be validated by conducting large-sample, high-quality RCT studies.
Yield and nutritive value of Stylosanthes spp. genotypes subjected to different harvest frequencies and seasons of the year
Authors: Diniz W. P. S. , Santos M. V. F. , Cunha M. V. , Lira Junior M. A. , Simões Neto D. E. , Oliveira O. F. , Leal G. G. , Mello A. C. L. , Santos L. S.
Published: January 2024

Productive and nutritional traits of forage species in various regions worldwide depend on different management strategies. This study aimed to evaluate the effects of harvest frequency (56, 77 and 98 days) and season of the year (rainy and dry) on the nutritional value and fractionation of carbohydrates and proteins of Stylosanthes genotypes (S. seabrana, S. scabra, S. mucronata and Stylosanthes spp. cv. Campo Grande). The experiment was conducted using a randomized complete block design with a split-plot arrangement and four repetitions. Contents of neutral detergent fibre (NDF), acid detergent fibre (ADF), in vitro digestible dry matter (IVDDM), condensed tannins and total phenolic compounds were influenced by the interaction of harvest frequency and season of the year. The 98-day harvest frequency resulted in lower IVDDM (579 g/kg) due to the high NDF and ADF concentrations during the rainy season. S. seabrana and S. scabra showed a higher proportion of A + B1 and B2 carbohydrate fractions, while the C fraction in the rainy season was greater in the Campo Grande, resembling S. seabrana. S. scabra displayed 15% of the crude protein in fraction A. The bromatological traits of Stylosanthes spp. did not decline sharply owing to plant age advancement, indicating these genotypes are suitable for forage production systems in tropical or semiarid regions.
Introduction: The Balkans
Authors: Nielsen Christian Axboe
Published: January 2024

This journal has in recent years published the Spotlight series, consisting of articles which each attempt to provide an overview of the historiographical landscape in various European countries and major themes in European history. The articles have highlighted methodological developments, significant debates, and risks and challenges to historical scholarship from hostile political directions. To date, the series has included profiles of Ukrainian, Norwegian, Albanian, Hungarian, Italian, Serbian and French history, as well as insightful overviews of right-wing populism, migration history, and environmental and global history.
Democracy, Authoritarianism and Global Economic Governance
Authors: Gautier Morin Johanna
Published: January 2024

Four weeks after Russia's invasion of Ukraine, US Senator John Kennedy accused the Biden administration of indirectly providing over $17 billion to Moscow as Putin was gearing up for war. In August 2021, the International Monetary Fund had indeed approved a historic $650 billion allocation of Special Drawing Rights to help member countries struggling with the Covid crisis. Russia benefited from these money transfers, as did Iran, China, and Myanmar, notwithstanding the authoritarian consolidation of these regimes. Kennedy's op-ed sparked a debate about the lack of transparency in the use of crisis resources and led to the adoption in the United States of the ‘Russia and Belarus SDR Exchange Prohibition Act’, which bans currency transactions with these countries through the IMF, following the imposition of 2,500 sanctions by the US Treasury since February 2022. The op-ed also reignited a decades-old debate over whether international organisations such as the IMF, World Bank and World Trade Organisation (WTO) should be held accountable for supporting authoritarian and corrupt governments or interfering in the politics of sovereign nations.
“I Just Told Them Like It Was”: Performance and History at Colonial Williamsburg
Authors: Gentry Philip
Published: January 2024

Since its organization in the mid-twentieth century, Colonial Williamsburg (CW) has been an important site for the consolidation of powerful narratives of American exceptionalism, patriotism, and the so-called consensus history of the American Revolution. This article looks at the role that music and performance has played in this historiography, taking as its primary texts two films produced by CW: The Story of a Patriot (1957) and The Music of Williamsburg (1960). With musical contributions by Bernard Herrmann and Alan Lomax, respectively, these films offer an opportunity to analyze the relationship between history and politics in the early Cold War era. Although The Story of a Patriot reflects a static and essentially conservative portrayal of American exceptionalism, the more liberal inclusiveness of The Music of Williamsburg showcases the fraught power dynamics of attempting to showcase historical Black music making in a patriotic context.
Exploring Hindu ethics of warfare: The Purāṇas
Authors: Balkaran Raj , Dorn A. Walter
Published: January 2024

What rules of fighting (armed combat) does Hinduism espouse? The sacred texts are the pre-eminent sources, so these need to be summarized and compared to each other. Teaching mostly through stories, the texts describe deeds of people (especially warriors), gods and demons to show how to behave and not to behave in war. While the injunctions in the Mahābhārata and Arthaśāstra are already covered in the literature, including in this journal, this present work examines the Purāṇas in depth. After a thorough search of all relevant passages, we find the Purāṇas to be very similar to the epics in terms of the list of prescribed and proscribed actions in war that they provide. We also make comparisons to international humanitarian law (IHL); as in the epics, we find that the Purāṇas contain many similar provisions to those found in IHL but that they go above and beyond what is required by IHL in urging that fighting be fair at the tactical level (i.e., between individual fighters). Being religious texts, the Purāṇas also deal with the afterlife consequences of both righteous and unrighteous combat.
Improved Surface Urban Heat Impact Assessment Using GOES Satellite Data: A Comparative Study With ERA‐5
Authors: Lee Jangho , Dessler Andrew E.
Published: January 2024

We compare high‐resolution land‐surface temperature (LST) estimates from the GOES‐16/17 (GOES) satellites to ERA‐5 Land (ERA‐5) reanalysis data across nine large US cities. We quantify the offset and find that ERA‐5 generally overestimates LST compared to GOES by 1.63°C. However, this overestimation is less pronounced in urban areas, underscoring the limitations of ERA‐5 in capturing the LST gradient between urban and non‐urban areas. We then examine three quantities: Surface Urban Heat Island Intensity (SUHII), extreme LST events, and LST exposure by population. We find that ERA‐5 does not accurately represent the diurnal variation and magnitude of SUHII in GOES. Furthermore, while ERA‐5 was on average too warm, ERA‐5 underestimates extreme heat by an average of 2.40°C. Our analysis reveals higher population exposure to high LST in the GOES data set across the cities studied. This discrepancy is especially pronounced when estimating the population fraction that are most exposed to heat.
Clinical characteristics and outcomes of children, adolescents and young adults with overweight or obesity and mental health disorders
Authors: Galler Angela , Thönnes Angelika , Joas Jens , Joisten Christine , Körner Antje , Reinehr Thomas , Röbl Markus , Schauerte Gerd , Siegfried Wolfgang , Weghuber Daniel , Weihrauch-Blüher Susann , Wiegand Susanna , Holl Reinhard W. , Prinz Nicole ,   APV Initiative
Published: January 2024

Background

Mental disorders are important comorbidities in youth with obesity. Aim was to describe the clinical characteristics and outcome of youth with overweight or obesity having comorbid mental disorders.

Methods

Data from children, adolescents, and young adults (age 6–30 years) with overweight or obesity and mental disorders (depression, anxiety disorder, eating disorder, attention deficit disorder (ADHD)) from 226 centers in Germany and Austria participating in the Adiposity Patient Registry (APV) were analyzed and compared with those without reported mental disorders using regression modeling.

Results

Mental health comorbidity was reported in a total of 3969 out of 114,248 individuals with overweight or obesity: 42.5% had ADHD, 31.3% anxiety disorders, 24.3% depression, and 12.9% eating disorders. Being male (OR 1.39 (95%CI 1.27;1.52)), of older age (1.42 (1.25;1.62)), or with extreme obesity (1.45 (1.30;1.63)) were most strongly associated with mental health comorbidity. Regression analysis showed that mean BMI-SDS was significantly higher in the group of individuals with depression and eating disorders (BMI-SDS 2.13 (lower; upper mean:2.09;2.16) and 2.22 (2.17;2.26)) compared to those without reported mental health comorbidity (BMI-SDS 2.008 (2.005;2.011); p < 0.001). In youth with ADHD, BMI-SDS was lower compared to those without reported mental disorders (BMI-SDS 1.91 (1.89;1.93) vs 2.008 (2.005;2.011); p < 0.001). Proportion of severe obesity was higher in individuals with depression (23.7%), anxiety disorders (17.8%), and eating disorders (33.3%), but lower in ADHD (10.3%), compared to those without reported mental disorders (13.5%, p < 0.002). Proportions of dyslipidaemia and abnormal carbohydrate metabolism were not different in youth with and without reported mental health comorbidity. BMI-SDS change after one year of lifestyle intervention program ranged between −0.22 and −0.16 and was similar in youth without and with different mental disorders.

Conclusion

Health care professionals caring for youth with overweight or obesity should be aware of comorbid mental disorders and regular mental health screening should be considered.
Adult hypertension referral pathway and therapeutic management: British and Irish Hypertension Society position statement
Authors: Lewis Philip , George Jacob , Kapil Vikas , Poulter Neil R. , Partridge Sarah , Goodman James , Faconti Luca , McCormack Terry , Wilkinson Ian B.
Published: January 2024

In the UK, most adults with hypertension are managed in Primary Care. Referrals to Secondary Care Hypertension Specialists are targeted to patients in whom further investigations are likely to change management decisions. In this position statement the British and Irish Hypertension Society provide clinicians with a framework for referring patients to Hypertension Specialists. Additional therapeutic advice is provided to optimise patient management whilst awaiting specialist review. Our aim is to ensure that referral criteria to Hypertension Specialists are consistent across the UK and Ireland to ensure equitable access for all patients.
Bidirectional association between autoimmune disease and perinatal depression: a nationwide study with sibling comparison
Authors: Bränn Emma , Chen Yufeng , Song Huan , László Krisztina D. , D’Onofrio Brian M. , Hysaj Elgeta , Almqvist Catarina , Larsson Henrik , Lichtenstein Paul , Valdimarsdottir Unnur A. , Lu Donghao
Published: January 2024

Although major depression, characterized by a pro-inflammatory profile, genetically overlap with autoimmune disease (AD) and the perinatal period involve immune system adaptations and AD symptom alterations, the bidirectional link between perinatal depression (PND) and AD is largely unexplored. Hence, the objective of this study was to investigate the bidirectional association between PND and AD. Using nationwide Swedish population and health registers, we conducted a nested case-control study and a matched cohort study. From 1,347,901 pregnancies during 2001–2013, we included 55,299 incident PND, their unaffected full sisters, and 10 unaffected matched women per PND case. We identified 41 subtypes of AD diagnoses recorded in the registers and compared PND with unaffected population-matched women and full sisters, using multivariable regressions. Women with an AD had a 30% higher risk of subsequent PND (95% CI 1.2–1.5) and women exposed to PND had a 30% higher risk of a subsequent AD (95% CI 1.3–1.4). Comparable associations were found when comparing exposed women with their unaffected sisters (nested case-control OR: 1.3, 95% CI 1.2–1.5, matched cohort HR: 1.3, 95% CI 1.1–1.6), and when studying antepartum and postpartum depression. The bidirectional association was more pronounced among women without psychiatric comorbidities (nested case-control OR: 1.5, 95% CI 1.4–1.6, matched cohort HR: 1.4, 95% CI 1.4–1.5) and strongest for multiple sclerosis (nested case-control OR: 2.0, 95% CI 1.6–2.3, matched cohort HR: 1.8, 95% CI 1.0–3.1). These findings demonstrate a bidirectional association between AD and PND independent of psychiatric comorbidities, suggesting possibly shared biological mechanisms. If future translational science confirms the underlying mechanisms, healthcare providers need to be aware of the increased risk of PND among women with ADs and vice versa.
Pediatric advocacy: Advancement in academic institutions
Authors: Bode Sara M. , Anwar Eimaan , Best Debra L. , Patel Mona , Beers Lee S. , Kaczorowski Jeffrey M. , Solomon Barry S. , Chamberlain Lisa J.
Published: January 2024

Impact

Children are facing many threats to their health today that require system change at a sweeping level to have real-world impact.

Pediatricians are positioned as natural leaders to advocate for these critical community and policy changes.

Academic medical center (AMC) leaders recognize the importance of this advocacy and clear steps can be taken to improve the structure to support pediatricians in their advocacy careers through faculty development and promotion, including standardized scholarly measurement of the outcomes.
A multi-center international study to evaluate the safety, functional and oncological outcomes of irreversible electroporation for the ablation of prostate cancer
Authors: Zhang Kai , Stricker Phillip , Löhr Martin , Stehling Michael , Suberville Michel , Cussenot Olivier , Lunelli Luca , Ng Chi-Fai , Teoh Jeremy , Laguna Pilar , de la Rosette Jean
Published: January 2024

Background

Irreversible electroporation (IRE) is a novel technique to treat localized prostate cancer with the aim of achieving oncological control while reducing related side effects. We present the outcomes of localized prostate cancer treated with IRE from a multi-center prospective registry.

Methods

Men with histologically confirmed prostate cancer were recruited to receive IRE. All the patients were proposed for prostate biopsy at 1-year post-IRE ablation. The functional outcomes were measured by the International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) questionnaires. The safety of IRE was graded by the treatment-related adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE).

Results

411 patients were recruited in this study from July 2015 to April 2020. The median follow-up time was 24 months (IQR 15–36). 116 patients underwent repeat prostate biopsy during 12–18 months after IRE. Clinically significant prostate cancer (Gleason ≥ 3 + 4) was detected in 24.1% (28/116) of the patients; any grade prostate cancers were found in 59.5% (69/116) of the patients. The IPSS score increased significantly from 7.1 to 8.2 (p = 0.015) at 3 months but decreased to 6.1 at 6 months (p = 0.017). Afterwards, the IPSS level remained stable during follow-up. The IIEF-5 score decreased at 3 months from 16.0 to 12.1 (p < 0.001) and then maintained equable afterwards. The rate of AEs was 1.8% at 3 months and then dropped to less than 1% at 6 months and remained stable until 48 months after IRE. Major AEs (Grade 3 or above) were rare.

Conclusion

For men with localized prostate cancer, IRE could achieve good urinary and sexual function outcomes and a reasonable oncological result. The real-world data are consistent with earlier studies, including recently published randomized controlled studies. The long-term oncological results need further investigation and follow-up.
Med23 deficiency reprograms the tumor microenvironment to promote lung tumorigenesis
Authors: Fu Xiaobo , Liu Siming , Cao Dan , Li Chonghui , Ji Hongbin , Wang Gang
Published: January 2024

Background

Lung cancer is the leading cause of cancer-related death worldwide. We previously found that Mediator complex subunit 23 (MED23) is important for the tumourigenicity of lung cancer cells with hyperactive Ras activity in vitro, although the in vivo function of MED23 in lung tumourigenesis remains to be explored.

Methods

In this study, we utilized well-characterized KrasG12D-driven non-small cell lung cancer mouse model to investigate the role of MED23 in lung cancer. The lung tumour progression was evaluated by H&E and IHC analysis. Western blotting and qRT-PCR assays were performed to detect changes in gene expression. Immune cells were analyzed by FACS technology. RNA-seq and reporter assays were conducted to explore the mechanism.

Results

We observed that lung epithelial Med23 deletion by adeno-Cre resulted in a significant increase in KrasG12D tumour number and size, which was further verified with another mouse model with Med23 specifically deleted in alveolar type II cells. Mice with lung-specific Med23 deficiency also exhibited accelerated tumourigenesis, and a higher proliferation rate for tumour cells, along with increased ERK phosphorylation. Notably, the numbers of infiltrating CD4+ T cells and CD8+ T cells were significantly reduced in the lungs of Med23-deficient mice, while the numbers of myeloid-derived suppressor cells (MDSCs) and Treg cells were significantly increased, suggesting the enhanced immune escape capability of the Med23-deficient lung tumours. Transcriptomic analysis revealed that the downregulated genes in Med23-deficient lung tumour tissues were associated with the immune response. Specifically, Med23 deficiency may compromise the MHC-I complex formation, partially through down-regulating B2m expression.

Conclusions

Collectively, these findings revealed that MED23 may negatively regulate Kras-induced lung tumourigenesis in vivo, which would improve the precise classification of KRAS-mutant lung cancer patients and provide new insights for clinical interventions.
Autoantibodies, antigen-autoantibody complexes and antigens complement CA125 for early detection of ovarian cancer
Authors: Young Han Chae , Bedia Jacob S. , Yang Wei-Lei , Hawley Sarah J. , Bergan Lindsay , Hopper Marika , Celestino Joseph , Guo Jing , Gornet Terrie G. , Soosaipillai Antoninus , Yang Hailing , Doskocil Samantha D. , Lokshin Anna E. , Handy Beverly C. , Diamandis Eleftherios P. , Moore Richard G. , Lu Karen H. , Lu Zhen , Anderson Karen S. , Drescher Charles W. , Skates Steven J. , Bast Robert C.
Published: January 2024

Background

Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer.

Methods

Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone.

Results

Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity. A four-biomarker panel including CA125, HE4, HE4 Ag-AAb and osteopontin detected 75% of early stage cancers in the validation set from among healthy controls compared to 62% with CA125 alone (p = 0.003) at 98% specificity. The same panel increased sensitivity for distinguishing early-stage ovarian cancers from benign pelvic masses by 25% (p = 0.0004) at 95% specificity. From 21 autoantibody candidates, 3 AAb (anti-p53, anti-CTAG1 and annt-Il-8) detected 22% of early stage ovarian cancers, potentially lengthening lead time prior to diagnosis.

Conclusion

A four biomarker panel achieved greater sensitivity at the same specificity for early detection of ovarian cancer than CA125 alone.
TNFα modulates PANX1 activation to promote ATP release and enhance P2RX7-mediated antitumor immune responses after chemotherapy in colorectal cancer
Authors: Huang Kevin Chih-Yang , Chiang Shu-Fen , Lin Pei-Chun , Hong Wei-Ze , Yang Pei-Chen , Chang Hui-Ping , Peng Shin-Lei , Chen Tsung-Wei , Ke Tao-Wei , Liang Ji-An , Chen William Tzu-Liang , Chao K. S. Clifford
Published: January 2024

ATP and its receptor P2RX7 exert a pivotal effect on antitumor immunity during chemotherapy-induced immunogenic cell death (ICD). Here, we demonstrated that TNFα-mediated PANX1 cleavage was essential for ATP release in response to chemotherapy in colorectal cancer (CRC). TNFα promoted PANX1 cleavage via a caspase 8/3-dependent pathway to enhance cancer cell immunogenicity, leading to dendritic cell maturation and T-cell activation. Blockade of the ATP receptor P2RX7 by the systemic administration of small molecules significantly attenuated the therapeutic efficacy of chemotherapy and decreased the infiltration of immune cells. In contrast, administration of an ATP mimic markedly increased the therapeutic efficacy of chemotherapy and enhanced the infiltration of immune cells in vivo. High PANX1 expression was positively correlated with the recruitment of DCs and T cells within the tumor microenvironment and was associated with favorable survival outcomes in CRC patients who received adjuvant chemotherapy. Furthermore, a loss-of-function P2RX7 mutation was associated with reduced infiltration of CD8+ immune cells and poor survival outcomes in patients. Taken together, these results reveal that TNFα-mediated PANX1 cleavage promotes ATP-P2RX7 signaling and is a key determinant of chemotherapy-induced antitumor immunity.
Use of the CONSIDER statement by eye health researchers when conducting and reporting research involving Indigenous peoples: an online survey
Authors: Samuels Isaac , Hamm Lisa M. , Silva Juan Carlos , Tousignant Benoit , Furtado João M. , Goodman Lucy , Watene Renata , Adams Jaki ,   Indigenous Eye Health Research Consortium, Yashadhana Aryati , Wilkinson Ben , Dimaras Helen , Brea Ilena , Rogers Jaymie , Black Joanna , Foreman Joshua , Arboleda Juan Camilo , Yee Juan Francisco , Trujillo Julián , Keay Lisa , Luque Luisa Casas , Oviedo-Cáceres María del Pilar , Saboya Martha , Alves Monica , Lichter Myrna , Silwal Pushkar , Findlay Rebecca , Barrenechea Rosario , Simkin Samantha , Bentley Sharon , Hopkins Shelley , Salomão Solange Rios , Misra Stuti , Fricke Tim , Reis Tulio , Ramke Jacqueline , Harwood Matire
Published: January 2024

Background

Indigenous peoples experience worse eye health compared to non-Indigenous peoples. Service providers and researchers must avoid perpetuating this inequity. To help achieve this, researchers can use the CONSolIDated critERia for strengthening the reporting of health research involving Indigenous peoples (CONSIDER) statement. This study aimed to identify the degree to which the CONSIDER statement has been used by eye health researchers when conducting and reporting research with an Indigenous component, and how they perceive its relevance in their future research.

Methods

We used purposive sampling to recruit eye health researchers from any country who have undertaken research with an Indigenous component. The online survey collected quantitative and qualitative data and was analysed using descriptive statistics and reflexive thematic analysis. Responses were gathered on a four-point Likert scale (1 to 4), with four being the most positive statement.

Results

Thirty-nine eye health researchers from nine countries completed the survey (Aotearoa New Zealand, Argentina, Australia, Brazil, Canada, Colombia, Guatemala, Panama, Peru); almost two-thirds (n = 24) undertake epidemiological research. On average, participants disclosed only ‘sometimes’ previously reporting CONSIDER items (2.26 ± 1.14), but they thought the items were relevant to eye health research and were motivated to use these guidelines in their future research. Some participants requested clarity about how CONSIDER aligned with existing guidelines, and when and how to apply the statement. Others shared rich experiences of the benefits to their research of Indigenous leadership and collaboration.

Conclusions

The CONSIDER statement is perceived as a valuable tool by these eye health researchers, and there are opportunities to maximise uptake and use, including increasing awareness of the statement, clarity about when it applies, and availability of institutional-level support.
Machine learning prediction of hepatic steatosis using body composition parameters: A UK Biobank Study
Authors: Boncan Delbert Almerick T. , Yu Yan , Zhang Miaoru , Lian Jie , Vardhanabhuti Varut
Published: January 2024

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease worldwide, yet detection has remained largely based on surrogate serum biomarkers, elastography or biopsy. In this study, we used a total of 2959 participants from the UK biobank cohort and established the association of dual-energy X-ray absorptiometry (DXA)-derived body composition parameters and leveraged machine learning models to predict NAFLD. Hepatic steatosis reference was based on MRI-PDFF which has been extensively validated previously. We found several significant associations with traditional measurements such as abdominal obesity, as defined by waist-to-hip ratio (OR = 2.50 (male), 3.35 (female)), android-gynoid ratio (OR = 3.35 (male), 6.39 (female)) and waist circumference (OR = 1.79 (male), 3.80 (female)) with hepatic steatosis. Similarly, A Body Shape Index (Quantile 4 OR = 1.89 (male), 5.81 (female)), and for fat mass index, both overweight (OR = 6.93 (male), 2.83 (female)) and obese (OR = 14.12 (male), 5.32 (female)) categories were likewise significantly associated with hepatic steatosis. DXA parameters were shown to be highly associated such as visceral adipose tissue mass (OR = 8.37 (male), 19.03 (female)), trunk fat mass (OR = 8.64 (male), 25.69 (female)) and android fat mass (OR = 7.93 (male), 21.77 (female)) with NAFLD. We trained machine learning classifiers with logistic regression and two histogram-based gradient boosting ensembles for the prediction of hepatic steatosis using traditional body composition indices and DXA parameters which achieved reasonable performance (AUC = 0.83–0.87). Based on SHapley Additive exPlanations (SHAP) analysis, DXA parameters that had the largest contribution to the classifiers were the features predicted with significant association with NAFLD. Overall, this study underscores the potential utility of DXA as a practical and potentially opportunistic method for the screening of hepatic steatosis.
Highly efficient capture approach for the identification of diverse inherited retinal disorders
Authors: Kao Hsiao-Jung , Lin Ting-Yi , Hsieh Feng-Jen , Chien Jia-Ying , Yeh Erh-Chan , Lin Wan-Jia , Chen Yi-Hua , Ding Kai-Hsuan , Yang Yu , Chi Sheng-Chu , Tsai Ping-Hsing , Hsu Chih-Chien , Hwang De-Kuang , Tsai Hsien-Yang , Peng Mei-Ling , Lee Shi-Huang , Chau Siu-Fung , Chen Chen Yu , Cheang Wai-Man , Chen Shih-Jen , Kwok Pui-Yan , Chiou Shih-Hwa , Lu Mei-Yeh Jade , Huang Shun-Ping
Published: January 2024

Our study presents a 319-gene panel targeting inherited retinal dystrophy (IRD) genes. Through a multi-center retrospective cohort study, we validated the assay’s effectiveness and clinical utility and characterized the mutation spectrum of Taiwanese IRD patients. Between January 2018 and May 2022, 493 patients in 425 unrelated families, all initially suspected of having IRD without prior genetic diagnoses, underwent detailed ophthalmic and physical examinations (with extra-ocular features recorded) and genetic testing with our customized panel. Disease-causing variants were identified by segregation analysis and clinical interpretation, with validation via Sanger sequencing. We achieved a read depth of >200× for 94.2% of the targeted 1.2 Mb region. 68.5% (291/425) of the probands received molecular diagnoses, with 53.9% (229/425) resolved cases. Retinitis pigmentosa (RP) is the most prevalent initial clinical impression (64.2%), and 90.8% of the cohort have the five most prevalent phenotypes (RP, cone-rod syndrome, Usher’s syndrome, Leber’s congenital amaurosis, Bietti crystalline dystrophy). The most commonly mutated genes of probands that received molecular diagnosis are USH2A (13.7% of the cohort), EYS (11.3%), CYP4V2 (4.8%), ABCA4 (4.5%), RPGR (3.4%), and RP1 (3.1%), collectively accounted for 40.8% of diagnoses. We identify 87 unique unreported variants previously not associated with IRD and refine clinical diagnoses for 21 patients (7.22% of positive cases). We developed a customized gene panel and tested it on the largest Taiwanese cohort, showing that it provides excellent coverage for diverse IRD phenotypes.
Cortical thickness and white matter microstructure predict freezing of gait development in Parkinson’s disease
Authors: Lin Fabin , Zou Xinyang , Su Jiaqi , Wan Lijun , Wu Shenglong , Xu Haoling , Zeng Yuqi , Li Yongjie , Chen Xiaochun , Cai Guofa , Ye Qinyong , Cai Guoen
Published: January 2024

The clinical applications of the association of cortical thickness and white matter fiber with freezing of gait (FoG) are limited in patients with Parkinson’s disease (PD). In this retrospective study, using white matter fiber from diffusion-weighted imaging and cortical thickness from structural-weighted imaging of magnetic resonance imaging, we investigated whether a machine learning-based model can help assess the risk of FoG at the individual level in patients with PD. Data from the Parkinson’s Disease Progression Marker Initiative database were used as the discovery cohort, whereas those from the Fujian Medical University Union Hospital Parkinson’s Disease database were used as the external validation cohort. Clinical variables, white matter fiber, and cortical thickness were selected by random forest regression. The selected features were used to train the support vector machine(SVM) learning models. The median area under the receiver operating characteristic curve (AUC) was calculated. Model performance was validated using the external validation cohort. In the discovery cohort, 25 patients with PD were defined as FoG converters (15 men, mean age 62.1 years), whereas 60 were defined as FoG nonconverters (38 men, mean age 58.5 years). In the external validation cohort, 18 patients with PD were defined as FoG converters (8 men, mean age 66.9 years), whereas 37 were defined as FoG nonconverters (21 men, mean age 65.1 years). In the discovery cohort, the model trained with clinical variables, cortical thickness, and white matter fiber exhibited better performance (AUC, 0.67–0.88). More importantly, SVM-radial kernel models trained using random over-sampling examples, incorporating white matter fiber, cortical thickness, and clinical variables exhibited better performance (AUC, 0.88). This model trained using the above mentioned features was successfully validated in an external validation cohort (AUC, 0.91). Furthermore, the following minimal feature sets that were used: fractional anisotropy value and mean diffusivity value for right thalamic radiation, age at baseline, and cortical thickness for left precentral gyrus and right dorsal posterior cingulate gyrus. Therefore, machine learning-based models using white matter fiber and cortical thickness can help predict the risk of FoG conversion at the individual level in patients with PD, with improved performance when combined with clinical variables.
EPAC1 enhances brown fat growth and beige adipogenesis
Authors: Reverte-Salisa Laia , Siddig Sana , Hildebrand Staffan , Yao Xi , Zurkovic Jelena , Jaeckstein Michelle Y. , Heeren Joerg , Lezoualc’h Frank , Krahmer Natalie , Pfeifer Alexander
Published: January 2024

Brown adipose tissue (BAT) is a central thermogenic organ that enhances energy expenditure and cardiometabolic health. However, regulators that specifically increase the number of thermogenic adipocytes are still an unmet need. Here, we show that the cAMP-binding protein EPAC1 is a central regulator of adaptive BAT growth. In vivo, selective pharmacological activation of EPAC1 increases BAT mass and browning of white fat, leading to higher energy expenditure and reduced diet-induced obesity. Mechanistically, EPAC1 coordinates a network of regulators for proliferation specifically in thermogenic adipocytes, but not in white adipocytes. We pinpoint the effects of EPAC1 to PDGFRα-positive preadipocytes, and the loss of EPAC1 in these cells impedes BAT growth and worsens diet-induced obesity. Importantly, EPAC1 activation enhances the proliferation and differentiation of human brown adipocytes and human brown fat organoids. Notably, a coding variant ofRAPGEF3(encoding EPAC1) that is positively correlated with body mass index abolishes noradrenaline-induced proliferation of brown adipocytes. Thus, EPAC1 might be an attractive target to enhance thermogenic adipocyte number and energy expenditure to combat metabolic diseases.
Parity–time-symmetric photonic topological insulator
Authors: Fritzsche Alexander , Biesenthal Tobias , Maczewsky Lukas J. , Becker Karo , Ehrhardt Max , Heinrich Matthias , Thomale Ronny , Joglekar Yogesh N. , Szameit Alexander
Published: January 2024

Topological insulators are a concept that originally stems from condensed matter physics. As a corollary to their hallmark protected edge transport, the conventional understanding of such systems holds that they are intrinsically closed, that is, that they are assumed to be entirely isolated from the surrounding world. Here, by demonstrating a parity–time-symmetric topological insulator, we show that topological transport exists beyond these constraints. Implemented on a photonic platform, our non-Hermitian topological system harnesses the complex interplay between a discrete coupling protocol and judiciously placed losses and, as such, inherently constitutes an open system. Nevertheless, even though energy conservation is violated, our system exhibits an entirely real eigenvalue spectrum as well as chiral edge transport. Along these lines, this work enables the study of the dynamical properties of topological matter in open systems without the instability arising from complex spectra. Thus, it may inspire the development of compact active devices that harness topological features on-demand.
Health effects associated with exposure to secondhand smoke: a Burden of Proof study
Authors: Flor Luisa S. , Anderson Jason A. , Ahmad Noah , Aravkin Aleksandr , Carr Sinclair , Dai Xiaochen , Gil Gabriela F. , Hay Simon I. , Malloy Matthew J. , McLaughlin Susan A. , Mullany Erin C. , Murray Christopher J. L. , O’Connell Erin M. , Okereke Chukwuma , Sorensen Reed J. D. , Whisnant Joanna , Zheng Peng , Gakidou Emmanuela
Published: January 2024

Despite a gradual decline in smoking rates over time, exposure to secondhand smoke (SHS) continues to cause harm to nonsmokers, who are disproportionately children and women living in low- and middle-income countries. We comprehensively reviewed the literature published by July 2022 concerning the adverse impacts of SHS exposure on nine health outcomes. Following, we quantified each exposure–response association accounting for various sources of uncertainty and evaluated the strength of the evidence supporting our analyses using the Burden of Proof Risk Function methodology. We found all nine health outcomes to be associated with SHS exposure. We conservatively estimated that SHS increases the risk of ischemic heart disease, stroke, type 2 diabetes and lung cancer by at least around 8%, 5%, 1% and 1%, respectively, with the evidence supporting these harmful associations rated as weak (two stars). The evidence supporting the harmful associations between SHS and otitis media, asthma, lower respiratory infections, breast cancer and chronic obstructive pulmonary disease was weaker (one star). Despite the weak underlying evidence for these associations, our results reinforce the harmful effects of SHS on health and the need to prioritize advancing efforts to reduce active and passive smoking through a combination of public health policies and education initiatives.