bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence, perinatal outcomes and factors associated with neonatal sepsis in Nigeria
Authors: Onubogu Chinyere Ukamaka , Ekwochi Uchenna , Obumneme‐Anyim Ijeoma , Nwokeji‐Onwe Linda Nneka , Eleje George Uchenna , Ojiegbe Nnabuike Okechukwu , Ezebialu Ifeanyichukwu Uzoma , Ezenkwele Eziamaka Pauline , Nzeribe Emily Akuabia , Umeh Uchenna Anthony , Ugwu Innocent Anayochukwu , Chianakwana Ogochukwu , Ibekwe Nkechi Theresa , Ezeaku Onyebuchi Ignatius , Ekweagu Gloria Nwuka , Onwe Abraham Bong , Lavin Tina , Ezekwe Bose , Settecase Eugenia , Tukur Jamilu , Ikechebelu Joseph Ifeanyichukwu
Published: April 2024

Objective

To examine the prevalence, perinatal outcomes and factors associated with neonatal sepsis in referral‐level facilities across Nigeria.

Design

Secondary analysis of data from the Maternal and Perinatal Database for Quality, Equity and Dignity Programme in 54 referral‐level hospitals across Nigeria.

Setting

Records covering the period from 1 September 2019 to 31 August 2020.

Population

Mothers admitted for birth during the study period, and their live newborns.

Methods

Analysis of prevalence and sociodemographic and clinical factors associated with neonatal sepsis and perinatal outcomes. Multilevel logistic regression modelling identified factors associated with neonatal sepsis.

Main outcome measures

Neonatal sepsis and perinatal outcomes.

Results

The prevalence of neonatal sepsis was 16.3 (95% CI 15.3–17.2) per 1000 live births (1113/68 459) with a 10.3% (115/1113) case fatality rate. Limited education, unemployment or employment in sales/trading/manual jobs, nulliparity/grand multiparity, chronic medical disorder, lack of antenatal care (ANC) or ANC outside the birthing hospital and referral for birth increased the odds of neonatal sepsis. Birthweight of <2500 g, non‐spontaneous vaginal birth, preterm birth, prolonged rupture of membranes, APGAR score of <7 at 5 min, birth asphyxia, birth trauma or jaundice were associated with neonatal sepsis. Neonates with sepsis were more frequently admitted to a neonatal intensive care unit (1037/1110, 93.4% vs 8237/67 346, 12.2%) and experienced a higher rate of death (115/1113, 10.3% vs 933/67 343, 1.4%).

Conclusions

Neonatal sepsis remains a critical challenge in neonatal care, underscored by its high prevalence and mortality rate. The identification of maternal and neonatal risk factors underscores the importance of improved access to education and employment for women and targeted interventions in antenatal and intrapartum care.
The shock index predicts in‐flight blood transfusion in aeromedical trauma patients
Authors: Powell Benjamin , Cramb Susanna
Published: April 2024

Objective

To define the utility of the Triage Revised Trauma Score (TRTS), GCS/Age/arterial Pressure (GAP) score, and shock index (SI) in predicting the need for in‐flight blood product administration in civilian trauma patients transported by an aeromedical platform.

Methods

A retrospective chart review of 3582 aeromedical trauma cases was conducted. An initial TRTS, GAP score and SI were calculated for each patient, and the administration of in‐flight blood products was also recorded. Receiver operating characteristic (ROC) curves were used to quantify the predictive discrimination of the TRTS, GAP score and SI on the need for in‐flight blood product administration.

Results

The SI showed a superior predictive value compared to the TRTS and GAP score. The SI showed an area under the curve on the ROC curve of 0.85 in both primary and inter‐hospital transfer cases, indicating reasonable predictive value.

Conclusion

The SI demonstrates favourable test characteristics for predicting the need for in‐flight blood product administration. Prospective validation of these results is warranted.
Acetylation of the polysaccharide from Houttuynia cordata rhizome and their α‐glucosidase inhibition mechanism
Authors: He Mengyao , Tang Shuxin , Xu Tingting , Yuan Yanan , Wu Ting , Pan Siyi , Xu Xiaoyun
Published: April 2024

In this study, the polysaccharide (RHCP) extracted from Houttuynia cordata rhizome was acetylated through the acetic anhydride method. The physicochemical properties of RHCP and its acetylated derivatives (Ac‐RHCP) were determined by infrared spectra, scanning electron microscopy, and Congo red test. Meanwhile, the α‐glucosidase inhibition mechanism of RHCP and Ac‐RHCP was analyzed by inhibition kinetics, and circular dichroism and fluorescence spectroscopy. Ac‐RHCP resulted in a more porous surface structure and 1.83‐fold higher solubility compared with RHCP. At a concentration of 6 mg/mL, the α‐glucosidase inhibition rate of Ac‐RHCP was 75.40%, while that of RHCP was 44.68%. RHCP and Ac‐RHCP inhibited α‐glucosidase in a mixed‐type manner, reduced the endogenous fluorescence of α‐glucosidase, affected the microenvironment of amino acid residues, and changed the conformation of α‐glucosidase. The study indicates that Ac‐RHCP exhibits a certain level of α‐glucosidase inhibition, demonstrating its potential as a functional food for glycemic control.
Quantification of flavonoids, minerals, and pigments present in “Nanicão” bananas during the ripening process
Authors: de Souza Angela Vacaro , Favaro Vitória Ferreira da Silva , de Mello Jéssica Marques , dos Santos Felipe André , Dall'Antonia Giseli Boiam , Vicente Eduardo Festozo
Published: April 2024

Banana is one of the most consumed and popular fruits in all regions of the world, being cultivated mainly in tropical countries. It is not only a rich source of vitamins A, C, and B, calcium, iron, potassium, phosphorus, and other vitamins and nutrients, but it also contains several types of antioxidants with high nutritional value. In this context, the current study aimed to quantify the content of ascorbic acid, flavonoids, pigments, and minerals present in “Nanicão” bananas during the ripening process. As demonstrated, the level of flavonoids was higher in ripe and overripe fruits, whereas the mineral composition was high only at ripening stage 4 (more yellow than green) a stage that should be prioritized when recommending fruit consumption to the population deficient in these minerals. Regarding pigments, there was a reduction in chlorophylls a and b and an increase in carotenoids and anthocyanins in peels and pulps.

Practical Application

Flavonoids are phenolic, bioactive compounds with proven antioxidant and anti‐inflammatory activity and products of the plant's secondary metabolism. The degradation of chlorophylls and synthesis of carotenoids and anthocyanins, and as a consequence of the latter pigment, the increase in flavonoids in the pulp was evident during the monitoring of ripening, mainly in the fruit peels in relation to pigments. Minerals are essential elements, the main ones provided in balanced diets and important for dietary and nutritional health.
Mechanical properties, sustained release, and oxygen scavenging properties of nanocomposite films loaded with bimetallic nanoparticles (Fe2O3/TiO2) in extra virgin olive oil
Authors: Kheirandish Mahsa , Javanmard dakheli Majid , Mizani Maryam , Salehirad Alireza
Published: April 2024

The aim of this study was the synthesis of bimetallic nanoparticles based on Fe2O3/TiO2 and its use in the poly(lactic acid) (PLA) films as an oxygen scavenger in extra virgin olive oil (EVOO) packaging. Bimetallic nanocomposites were prepared by two different precipitation methods (precipitation with ammonia and sodium hydroxide). The characteristics of bimetallic nanoparticles precipitated with sodium hydroxide (Na‐Ti0.01Fe0.048O0.08) and bimetallic nanoparticles precipitated with ammonia (NH‐Ti0.01Fe0.022O0.09) were compared. Relative amounts of elements in bimetallic nanocomposites and their morphological characteristics were determined using field emission scanning electron microscopy coupled with energy‐dispersive X‐ray spectrometer. Porosity volume and surface area of bimetallic nanoparticles were calculated using adsorption–desorption isotherms and the Brunauer–Emmett–Teller method. The formation/characterization of bimetallic nanoparticles and their location in the matrix of PLA‐based nanocomposite film was studied using X‐ray diffraction and Fourier transform infrared. In nanocomposite films based on PLA, bimetallic nanoparticles lead to better oxidative stability (peroxide value, p‐anisidine index, K232, and K270) of the EVOO and oxygen scavenging during storage compared to free nanoparticles. Mechanical properties of nanocomposite films were improved due to bimetallic nanoparticles, which were better for Na‐Ti0.01Fe0.048O0.08. In vitro release modeling of the bimetallic nanoparticles in EVOO proved that Fickian diffusion is the dominant mechanism, and the Peleg model was the best description of the release behavior of nanoparticles.
Independent and interactive associations of heart rate and obesity with type 2 diabetes mellites: A population‐based study
Authors: Zhu Tianxin , Chen Qingyu , Chen Hongxing , You Lili , Liu Dan , Zhang Xiaoyun , Li Feng , Wu Hongshi , Tang Juying , Lin Diaozhu , Sun Kan , Yan Li , Ren Meng
Published: April 2024

Background

Although obesity and heart rate (HR) were closely related to the prevalence and development of type 2 diabetes mllitus (T2DM), few studies have shown a co‐association effect of them on T2DM. We aimed at assessing the interactive effects of HR and obesity with prevalence of T2DM in Chinese population, providing the exact cutpoint of the risk threshold for blood glucose with high HR.

Materials and Methods

In the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study (REACTION) cohorts (N = 8398), the relationship between HR and T2DM was explored by linear regression, logistic regression, and restricted cubic spline, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Interaction terms between HR and body mass index (BMI) and HR and waist circumference (WC) were introduced into the logistic regression model.

Results

In those with HR > 88.0 beats/min, fasting plasma glucose and oral glucose tolerance tests were significantly correlated with HR, and the prevalence of T2DM was highly correlated with HR (all p < .05). There were interactive associations of HR and obesity in patients with T2DM with HR < 74 beats/min.

Conclusion

High HR was in interaction with obesity, associating with prevalence of T2DM. The newly subdivided risk threshold for HR with T2DM might be HR > 88 beats/minute.

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Association of obstructive sleep apnea symptoms with all‐cause mortality and cause‐specific mortality in adults with or without diabetes: A cohort study based on the NHANES
Authors: Zhang Qian , Zhang Qi , Li Xiaomin , Du Gang , Feng Xiaojin , Ding Runtao , Chi Yuhua , Liu Yongping
Published: April 2024

Background

The association between obstructive sleep apnea syndrome (OSAS) and mortality has not been extensively researched among individuals with varying diabetic status. This study aimed to compare the relationship of OSAS with all‐cause and cause‐specific mortality in US individuals with or without diabetes based on data from the National Health and Nutrition Examination Survey (NHANES).

Methods

The study included participants from the NHANES 2005–2008 and 2015–2018 cycles with follow‐up information. OSAS data (OSAS.MAP10) was estimated from the questionnaire. Hazard ratios (HRs) and the 95% confidence interval (CI) of OSAS for mortality were calculated by Cox regression analysis in populations with different diabetes status. The relationships between OSAS and mortality risk were examined using survival curves and restricted cubic spline curves.

Results

A total of 13 761 participants with 7.68 ± 0.042 follow‐up years were included. In the nondiabetic group, OSAS.MAP10 was positively associated with all‐cause, cardiovascular, and cancer mortality. In individuals with prediabetes, OSAS.MAP10 was positively related to all‐cause mortality (HR 1.11 [95% CI: 1.03–1.20]) and cardiovascular mortality (HR 1.17 [95% CI: 1.03–1.33]). The relationship between OSAS.MAP10 and the risk of all‐cause mortality and cancer mortality exhibited L‐shaped curves in diabetes patients (both with nonlinear p values <.01). Further threshold effect analysis revealed that OSAS was positively related to death risk when OSAS.MAP10 exceeded the threshold scores.

Conclusion

The relationship between OSAS and mortality differed among participants with or without diabetes. Individualized clinical treatment plans should be developed in clinical practice to reduce the risk of death for patients with different metabolic conditions.

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Kisspeptin a potential therapeutic target in treatment of both metabolic and reproductive dysfunction
Authors: Sliwowska Joanna Helena , Woods Nicola Elizabeth , Alzahrani Abdullah Rzgallah , Paspali Elpiniki , Tate Rothwelle Joseph , Ferro Valerie Anne
Published: April 2024

Kisspeptins (KPs) are proteins that were first recognized to have antimetastatic action. Later, the critical role of this peptide in the regulation of reproduction was proved. In recent years, evidence has been accumulated supporting a role for KPs in regulating metabolic processes in a sexual dimorphic manner. It has been proposed that KPs regulate metabolism both indirectly via gonadal hormones and/or directly via the kisspeptin receptor in the brain, brown adipose tissue, and pancreas. The aim of the review is to provide both experimental and clinical evidence indicating that KPs are peptides linking metabolism and reproduction. We propose that KPs could be used as a potential target to treat both metabolic and reproductive abnormalities. Thus, we focus on the consequences of disruptions in KPs and their receptors in metabolic conditions such as diabetes, undernutrition, obesity, and reproductive disorders (hypogonadotropic hypogonadism and polycystic ovary syndrome). Data from both animal models and human subjects indicate that alterations in KPs in the case of metabolic imbalance lead also to disruptions in reproductive functions. Changes both in the hypothalamic and peripheral KP systems in animal models of the aforementioned disorders are discussed. Finally, an overview of current clinical studies involving KP in fertility and metabolism show fewer studies on metabolism (15%) and only one to date on both. Presented data indicate a dynamic and emerging field of KP studies as possible therapeutic targets in treatments of both reproductive and metabolic dysfunctions.

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Russia–Ukraine war and India's quest for leading power status
Authors: Verma Raj
Published: April 2024

India's neutrality and failure to publicly criticise Russia is driven by the Modi government's quest to be a great/leading power. It believes that Moscow can aid New Delhi in achieving this goal by enhancing the security pillar of its foreign policy strategy. However, publicly criticising Russia will undermine India's security pillar and will prevent India from becoming a leading power. Thus, India's response to the Ukraine war might be best described as ‘varied consequentialism’. Additionally, India has also exhibited ‘strategic opportunism’; that is, it has employed norms and values strategically to pursue its aspirations to emerge as a leading power. It has sought to use the Global South's discontent with the US‐led Western liberal order aggravated by the Russia–Ukraine war, to seek leadership of the Global South. It seeks to act as the leader of a new ‘non‐alignment’, which has emerged as a consequence of the war.
Private sector participation in infrastructure in emerging market and developing economies: Evolution, constraints, and policies
Authors: Mawejje Joseph
Published: April 2024

The private sector can play important roles in closing the infrastructure investment gaps in emerging market and developing economies. However, private participation in emerging market and developing economies' infrastructure has declined over the past decade, reflecting persistent structural challenges and risks in the business environment. The decline was broad‐based and gained momentum following the 2013 taper tantrum and the end of the commodity super cycle. Incentivizing greater private sector participation in infrastructure will require policies to improve access to long‐term finance and to derisk the business environment. This will require efforts to strengthen the banking sector regulation and supervision, to improve the legal and contractual environment, and to limit information asymmetries. Deepening local financial and bond markets can make it possible for infrastructure bonds to be issued in local currencies and minimize potential currency mismatches. Improvements in the broader business environment can benefit from greater macroeconomic stability and stronger institutional frameworks. Policies that improve the quality of projects at entry, address currency risk, relax capital controls, and enable cost recovery pricing can unlock private sector participation in infrastructure financing. Strong government support, including ensuring regulatory quality, and providing well‐targeted guarantees and subsidies, can play a critical role.
Digital nomadism and the challenge to social citizenship
Authors: Webb Adam K.
Published: April 2024

As a subset of remote work, digital nomadism crosses jurisdictions and generates fears that it unfairly escapes regulation and taxation. Alongside other circuits of an emerging world society, it fails to fit neatly into the longstanding template of relatively self‐contained nation‐states. Most efforts to address this new phenomenon merely aim to tweak tax treaties and other rules, so as better to slot mobile individuals back into existing schemes of regulation and redistribution. But digital nomadism suggests a more fundamental need to rethink the entire modern framework of social citizenship. Social citizenship bundles together immobile populations, territorial sovereignty, and the state as the main clearinghouse of justice and solidarity. In mapping out an alternative, this article draws on resources in political thought dealing with a plurality of spheres of life. Unbundling the strictly territorial functions of the state from other functions of risk‐sharing and solidarity would better correspond to the new and varied scales of cross‐border living.
Critical Archival Encounters and the Evolving Historiography of the Dismissal of the Whitlam Government
Authors: Hocking Jenny
Published: April 2024

Gough Whitlam was deeply committed to the preservation of history, and keenly attuned to the importance of the documentary record in the writing of it. For Whitlam, the written record — the contemporaneous documentary record of government activity — was central to the production of historical knowledge and the “verification” of history. As he reflected on the release of his government's 1975 Cabinet papers, “the publication of these records confirms my belief in the contemporary document as the primary source for writing and understanding history”. This paper takes us through the shifting historiography of the dismissal of the Whitlam government by Governor‐General Sir John Kerr. In doing so, it is a reflection also on the role of archives in the writing of history, recognising as Peters does, that the construction of an archival record is “a deeply political act”. This is particularly so for contested, polarised, episodes — of which the dismissal is surely the exemplar — for which archival records have been transformative. In this process of historical correction, revelations from Kerr's papers in the National Archives of Australia have been pivotal. Kerr's papers were also central to my successful legal action against the Archives securing the release of the “Palace letters” between Kerr and the Queen regarding the dismissal. This paper explores some critical “archival encounters” during that research journey — revelations, obstructions, missing archives, and even burnt archives. From the destruction of Whitlam's security file, missing Government House guestbooks, the denial of access to records, to royal letters of support for Kerr's dismissal of Whitlam “accidentally burnt” in the Yarralumla incinerator, these encounters illuminate the critical relationship between archives, access, and history which continue to shape our understanding of the dismissal of the Whitlam government.
Tourism‐induced growth and quality of life: the Singapore story
Authors: Tan Sook Rei , Wood Jacob , Jang Haejin , Wong Caroline , Li Changtai
Published: April 2024

The influx of international tourists may affect the economic growth of destination countries by influencing the quality of life (QoL) of residents, the effects of which are unclear ex ante. Therefore, this study utilises the autoregressive distributed lag model to examine tourism‐induced growth by taking into consideration the residents' QoL using Singapore as a case study. We also consider the factor of heterogeneous tourism demand by regions of origin in a market‐based analysis using seemingly unrelated regression, motivated by the assumption that consumers from different markets differ widely over their preferences. This study seeks to contribute to an understanding of tourism as a source of sustainable economic development and as such provides important policy implications for practitioners and scholars alike.
Accounting for future populations in health research
Authors: Pierson Leah
Published: April 2024

The research we fund today will improve the health of people who will live tomorrow. But future people will not all benefit equally: decisions we make about what research to prioritize will predictably affect when and how much different people benefit from research. Organizations that fund health research should thus fairly account for the health needs of future populations when setting priorities. To this end, some research funders aim to allocate research resources in accordance with disease burden, prioritizing illnesses that cause more morbidity and mortality. In this article, I defend research funders' practice of aligning research funding with disease burden but argue that funders should aim to align research funding with future—rather than present—disease burden. I suggest that research funders should allocate research funding in proportion to aggregated estimates of disease burden over the period when research could plausibly start to yield benefits until indefinitely into the future.
Prevention and treatment of infection in patients with an absent or hypofunctional spleen: A British Society for Haematology guideline
Authors: Ladhani Shamez N. , Fernandes Savio , Garg Mamta , Borrow Ray , de Lusignan Simon , Bolton‐Maggs Paula H. B. ,   the BSH Guidelines Committee
Published: April 2024

Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen were published by the British Committee for Standards in Haematology in 1996 and updated in 2002 and 2011. With advances in vaccinations and changes in patterns of infection, the guidelines required updating. Key aspects included in this guideline are the identification of patients at risk of infection, patient education and information and immunisation schedules. This guideline does not address the non‐infective complications of splenectomy or functional hyposplenism (FH). This replaces previous guidelines and significantly revises the recommendations related to immunisation. Patients at risk include those who have undergone surgical removal of the spleen, including partial splenectomy and splenic embolisation, and those with medical conditions that predispose to FH. Immunisations should include those against Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus) and influenza. Haemophilus influenzae type b (Hib) is part of the infant immunisation schedule and is no longer required for older hyposplenic patients. Treatment of suspected or proven infections should be based on local protocols and consider relevant anti‐microbial resistance patterns. The education of patients and their medical practitioners is essential, particularly in relation to the risk of serious infection and its prevention. Further research is required to establish the effectiveness of vaccinations in hyposplenic patients; infective episodes should be regularly audited. There is no single group ideally placed to conduct audits into complications arising from hyposplenism, highlighting a need for a national registry, as has proved very successful in Australia or alternatively, the establishment of appropriate multidisciplinary networks.
British Society for Haematology guidelines to improve the care of asplenic patients: Much work done, some remaining and a call for national registries
Authors: Rivière Etienne
Published: April 2024

Asplenic patients are at high risk of serious infectious or thrombotic complications, especially when they are not adequately informed of the risk and not closely followed. Ladhani et al. on behalf of the British Society for Haematology propose updated guidelines for managing these patients. Healthcare professionals need to improve infection prevention in patients with hypofunctional or absent spleen through better identification and immunisation using established national registries.

Commentary on: Ladhani et al. Prevention and treatment of infection in patients with absent or hypofunctional spleen: A British Society for Haematology guideline. Br J Haematol 2024;204:1672‐1686.
Revisiting the most often used item in the haematological tool box—The extent of haemodilution in bone marrow aspirates
Authors: Hokland Peter
Published: April 2024

In this issue, a nationwide retrospective Japanese study finds that, in a second opinion setting, one‐third of bone marrow aspirates from patients suspected of myelodysplastic syndromes are heavily haemodiluted. Moreover, in four‐fifths of such cases, the failure to obtain the correct material for diagnosis went undetected by the referring institution. These data are intriguing, but given their special set‐up, caution should be exerted in transposing them to other countries.

Commentary on: Ogata et al. Prevalence of massively diluted bone marrow cell samples aspirated from patients with myelodysplastic syndromes (MDS) or suspected MDS: A retrospective analysis of nationwide samples in Japan. Br J Haematol 2024;204:1856‐1861.
Bardoxolone methyl prevents metabolic dysfunction‐associated steatohepatitis by inhibiting macrophage infiltration
Authors: Onuma Kazuhiro , Watanabe Kenji , Isayama Keishiro , Ogi Sayaka , Tokunaga Yasunori , Mizukami Yoichi
Published: April 2024

Background and Purpose

Bardoxolone methyl (2‐cyano‐3,12‐dioxooleana‐1,9(11)‐dien‐28‐oic acid methyl ester, CDDO‐Me) is a potent activator of nuclear factor erythroid 2‐related factor 2 (Nrf2), which induces the expression of antioxidative‐associated genes. CDDO‐Me exerts protective effects against chronic inflammatory diseases in the kidneys and lungs. However, its pharmacological effects on metabolic dysfunction‐associated steatohepatitis (MASH) caused by fat accumulation remain unknown. In this study, we examined the hepatoprotective effects of CDDO‐Me in a diet‐induced MASH mouse model and elucidated its pharmacological mechanisms using RNA‐seq analysis.

Experimental Approach

CDDO‐Me was orally administered to mice fed a choline‐deficient, L‐amino acid‐defined, high‐fat diet (CDAHFD), and histological, biochemical, and transcriptomic analyses were performed on livers of mice that developed MASH.

Key results

CDDO‐Me administration induced the expression of antioxidant genes and cholesterol transporters downstream of Nrf2 and significantly prevented the symptoms of MASH. Whole‐transcriptome analysis revealed that CDDO‐Me inhibited the inflammatory pathway that led to phagocyte recruitment, in addition to activating the Nrf2‐dependent pathway. Among inflammatory pathways, CC chemokine ligands (CCL)3 and CCL4, which are downstream of NF‐κB and are associated with the recruitment of macrophages expressing CC chemokine receptors (CCR)1 and CCR5, were released into the blood in MASH mice. However, CDDO‐Me directly inhibited the expression of CCL3‐CCR1 and CCL4‐CCR5 in macrophages.

Conclusions and Implications

Overall, we revealed the potent hepatoprotective effect of CDDO‐Me in a MASH mouse model and demonstrated that its pharmacological effects were closely associated with a reduction of macrophage infiltration, through CCL3‐CCR1 and CCL4‐CCR5 inhibition, in addition to Nrf2‐mediated hepatoprotective effects.
Debate: CAMHS will be at the forefront of the next generation of psychosis risk models, but further integration with early intervention psychosis services is needed to realise this potential
Authors: Naughton Sean , Clarke Mary
Published: April 2024

The detection of psychosis and its prodrome have unique considerations in a child and adolescent population. Young people attending CAMHS are already a high‐risk group, which confers significant limitations in applying the current clinical high‐risk (CHR) model. This has catalysed calls for a transdiagnostic approach to psychosis risk prediction, but without a clear pathway forward. We contribute to the debate opened by Salazar de Pablo and Arango (2023, Child and Adolescent Mental Health) on the role of CAMHS in this initiative. CAMHS have a key role in developing comprehensive longitudinal datasets to inform risk models. Closer integration with early intervention in psychosis (EIP) services will be needed to realise this potential. This integration is also required to reliably detect prodromes and emerging psychosis in young people. Where there is robust evidence to support prevention initiatives, we should proceed with their implementation, even in the absence of enhanced risk models.
IMPROVE 2022 International Meeting on Pathway‐Related Obesity: Vision of Excellence
Authors: Kühnen Peter , Argente Jesús , Clément Karine , Dollfus Hélène , Dubern Béatrice , Farooqi Sadaf , de Groot Corjan , Grüters Annette , Holm Jens‐Christian , Hopkins Mark , Kleinendorst Lotte , Körner Antje , Meeker David , Rydén Mikael , von Schnurbein Julia , Tschöp Matthias , Yeo Giles S. H. , Zorn Stefanie , Wabitsch Martin
Published: April 2024

Nearly 90 clinicians and researchers from around the world attended the first IMPROVE 2022 International Meeting on Pathway‐Related Obesity. Delegates attended in person or online from across Europe, Argentina and Israel to hear the latest scientific and clinical developments in hyperphagia and severe, early‐onset obesity, and set out a vision of excellence for the future for improving the diagnosis, treatment, and care of patients with melanocortin‐4 receptor (MC4R) pathway‐related obesity. The meeting co‐chair Peter Kühnen, Charité Universitätsmedizin Berlin, Germany, indicated that change was needed with the rapidly increasing prevalence of obesity and the associated complications to improve the understanding of the underlying mechanisms and acknowledge that monogenic forms of obesity can play an important role, providing insights that can be applied to a wider group of patients with obesity. World‐leading experts presented the latest research and led discussions on the underlying science of obesity, diagnosis (including clinical and genetic approaches such as the role of defective MC4R signalling), and emerging clinical data and research with targeted pharmacological approaches. The aim of the meeting was to agree on the questions that needed to be addressed in future research and to ensure that optimised diagnostic work‐up was used with new genetic testing tools becoming available. This should aid the planning of new evidence‐based treatment strategies for the future, as explained by co‐chair Martin Wabitsch, Ulm University Medical Center, Germany.
Phosphorylation‐regulated phase separation of syndecan‐4 and syntenin promotes the biogenesis of exosomes
Authors: Zhao Tian , Yang Xiaolan , Duan Guangfei , Chen Jialin , He Kefeng , Chen Yong‐Xiang , Luo Shi‐Zhong
Published: April 2024

The biogenesis of exosomes that mediate cell‐to‐cell communication by transporting numerous biomolecules to neighbouring cells is an essential cellular process. The interaction between the transmembrane protein syndecan‐4 (SDC4) and cytosolic protein syntenin plays a key role in the biogenesis of exosomes. However, how the relatively weak binding of syntenin to SDC4 efficiently enables syntenin sorting for packaging into exosomes remains unclear. Here, we demonstrate for the first time that SDC4 can undergo liquid–liquid phase separation (LLPS) to form condensates both in vitro and in the cell membrane and that, the SDC4 cytoplasmic domain (SDC4‐CD) is a key contributor to this process. The phase separation of SDC4 greatly enhances the recruitment of syntenin to the plasma membrane (PM) despite the weak SDC4‐syntenin interaction, facilitating syntenin sorting for inclusion in exosomes. Interestingly, phosphorylation at the only serine (179) in the SDC4‐CD (Ser179) disrupts SDC4 LLPS, and inhibited phosphorylation or dephosphorylation restores the SDC4 LLPS to promote its recruitment of syntenin to the PM and syntenin inclusion into exosomes. This research reveals a novel phosphorylation‐regulated phase separation property of SDC4 in the PM through which SDC4 efficiently recruits cytosolic syntenin and facilitates the biogenesis of exosomes, providing potential intervention targets for exosome‐mediated biomedical events.
Retagliptin as add‐on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double‐blind, placebo‐controlled, phase 3 trial
Authors: Guo Lixin , Tian Fengsheng , Liu Li , Chen Mingwei , Jiang Chengxia , Li Shuangqing , Liu Cong , Zhang Yawei , Qin Jie , Yu Dongni , Zong Yicen , Dai Wei
Published: April 2024

Aim

To evaluate the efficacy and safety of retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin.

Materials and Methods

This multicentre, phase 3 trial consisted of a 16‐week, randomized, double‐blind, placebo‐controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once‐daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add‐on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16.

Results

At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was −0.82% (95% CI, −1.05% to −0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2‐hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported.

Conclusions

Retagliptin 100 mg QD as an add‐on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.
Genetic backgrounds and clinical characteristics of congenital neutropenias in Israel
Authors: Yeshareem Lital , Yacobovich Joanne , Lebel Asaf , Noy‐Lotan Sharon , Dgany Orly , Krasnov Tanya , Berger Pinto Galit , Oniashvili Nino , Mardoukh Jacques , Bielorai Bella , Laor Ruth , Mandel‐Shorer Noa , Ben Barak Ayelet , Levin Carina , Asleh Mahdi , Miskin Hagit , Revel‐Vilk Shoshana , Levin Dror , Benish Marganit , Zuckerman Tsila , Wolach Ofir , Pazgal Idit , Brik Simon Dafna , Gilad Oded , Yanir Asaf David , Goldberg Tracie Alison , Izraeli Shai , Tamary Hannah , Steinberg‐Shemer Orna
Published: April 2024

Background

Congenital neutropenias are characterized by severe infections and a high risk of myeloid transformation; the causative genes vary across ethnicities. The Israeli population is characterized by an ethnically diverse population with a high rate of consanguinity.

Objective

To evaluate the clinical and genetic spectrum of congenital neutropenias in Israel.

Methods

We included individuals with congenital neutropenias listed in the Israeli Inherited Bone Marrow Failure Registry. Sanger sequencing was performed for ELANE or G6PC3, and patients with wild‐type ELANE/G6PC3 were referred for next‐generation sequencing.

Results

Sixty‐five patients with neutropenia were included. Of 51 patients with severe congenital neutropenia, 34 were genetically diagnosed, most commonly with variants in ELANE (15 patients). Nine patients had biallelic variants in G6PC3, all of consanguineous Muslim Arab origin. Other genes involved were SRP54, JAGN1, TAZ, and SLC37A4. Seven patients had cyclic neutropenia, all with pathogenic variants in ELANE, and seven had Shwachman–Diamond syndrome caused by biallelic SBDS variants. Eight patients (12%) developed myeloid transformation, including six patients with an unknown underlying genetic cause. Nineteen (29%) patients underwent hematopoietic stem cell transplantation, mostly due to insufficient response to treatment with granulocyte‐colony stimulating factor or due to myeloid transformation.

Conclusions

The genetic spectrum of congenital neutropenias in Israel is characterized by a high prevalence of G6PC3 variants and an absence of HAX1 mutations. Similar to other registries, for 26% of the patients, a molecular diagnosis was not achieved. However, myeloid transformation was common in this group, emphasizing the need for close follow‐up.
Overexpressed FKBP5 mediates colorectal cancer progression and sensitivity to FK506 treatment via the NF‐κB signaling pathway
Authors: Liu Tiancong , Wang Changliang , Xia Zhixiu
Published: April 2024

Colorectal cancer (CRC) is a common and deadly tumor. FK506‐binding protein 5 (FKBP5) is associated with some cancers, but the role of FKBP5 in CRC is not clear. The present study aimed to reveal the relationship between FKBP5 and CRC and to uncover the roles of FK506 in CRC. In total, 96 CRC patients were recruited. Survival analysis was conducted using the Kaplan–Meier method and COX regression analyses. Bioinformatics analyses were performed to explore the functions of FKBP5. The mechanisms of FKBP5 and the roles of FK506 in CRC progression were clarified by immunohistochemistry, MTS, scratch assay, transwell and flow cytometric analyses via in vitro and in vivo experiments. FKBP5 was overexpressed in 77 cancer tissues compared to that in matched normal tissues, and the overall survival rate of these patients was relatively shorter. Bioinformatics analyses showed that FKBP5 regulates proliferation, invasion, migration, epithelial–mesenchymal transition and nuclear factor‐kappa B (NF‐κB) signaling. The upregulation or downregulation of FKBP5 dramatically increases or decreases the proliferation, invasion and migration abilities of CRC cells. The expression of NF‐κB, inhibitor B kinase α, matrix metalloproteinase‐2 and metalloproteinase‐9 positively correlated with FKBP5. FK506 inhibits the progression of CRC via the FKBP5/NF‐κB signaling pathway. Our study identified a regulatory role for FKBP5 in CRC progression. Therefore, targeting FKBP5 may provide a novel treatment approach for CRC. FK506 can inhibit the progression of CRC by restraining the FKBP5/NF‐κB signaling pathway and is expected to become a new drug for the treatment of CRC.
Petrogenesis of S‐type Ladakh granite and mafic microgranular enclaves in the southern margin of Ladakh batholith: An evidence of crust–mantle interaction during the collision between Indian and Eurasian plates
Authors: Perumalsamy C. , Vijay Anand S. , Nagarajan R. , Mukherjee Bappa
Published: April 2024

The previous studies revealed the I‐type Ladakh magmatism in the Andean‐type southern margin of the Ladakh batholith (LB) was related to the subduction of the Neotethyan Ocean and India‐Eurasia collision. However, LB's S‐type granitic magmatism and associated mafic microgranular enclaves (MMEs) are poorly constrained. Here, we present the new data for S‐type Ladakh granite (LG) and associated monzodiorite MMEs in the Andean‐type orogeny in the southern margin of the Eurasian plate. The low SiO2 (47.4–53.9 wt%), high K2O (1.56–3.21 wt%), Mg# (52–65), continental‐arc tracer patterns, and slightly depleted to evolved Sr‐Nd isotopic composition ((87Sr/86Sr)i = 0.7047–0.7166; ℇNd (t = 50 Ma) = (+1.40 to −8.92)) for MME suggest that they were derived from the phlogopite‐bearing deep lithospheric mantle‐source at a depth of 5.4–10.5 km depth with 810–870°C, 1.4–2.8 kbar, and enriched by sediment‐melts addition into the mantle‐wedge from subducting Neotethyan Oceanic slab. The mantle‐derived ascending hot mafic magma mixing with felsic magma of the ancient northern Indian margin‐derived, generates monzodiorite MME by assimilation and magma mixing processes. Plagioclase, amphibole, and biotite chemistry support the magma mixing processes. LG are characterized by high SiO2 (63.4–75.0 wt%), K2O (3.93–5.67 wt%), CaO/Na2O ratio of >0.3, differentiation index (90.27–97.46), normative corundum (1.0–2.8), A/CNK values (1.00–1.18), hypersthene (0.7–5.7), and low Al2O3, MgO, TiO2, Fe2O3. They also exhibit peraluminous, variable tracer elemental abundances, variable (87Sr/86Sr)i ratios (0.6967–0.7191), and high whole rock ℇNd (t = 50 Ma) values of −4.15 to −11.92) and ancient two‐stage Nd model age of 1160 and 1858 Ma. These features suggest that S‐type Ladakh granites were derived from the melting of ancient metagreywacke‐dominated metasedimentary rocks of the northern Indian margin by a large amount of mafic magma underplating after subducted Neotethyan slab‐rollback. The formation of LG and MMEs related to the Andean‐type orogeny in the southern margin of the Eurasian plate.
Lowering the synthesis temperature of α‐Al2O3 by increasing the content of pentacoordinate aluminum in the precursors
Authors: Wei Kaite , Ma Mingyuan , Lu Youjun , Wang Jian , Zhang Xiao , Liang Sen
Published: April 2024

α‐Al2O3, commonly known as corundum, plays a significant role in various industrial applications. Typically, the synthesis of α‐Al2O3 requires elevated temperatures exceeding 1200°C, which results in reduced specific surface area and increased particle size due to high‐temperature calcination. In this study, α‐Al2O3 powder was primarily investigated. The precursor was prepared by non‐hydrolytic sol‐gel (NHSG) method, employing alcohols and other nonaqueous oxygen donors in nucleophilic substitution reactions with AlCl3. The precursor was then processed by mechanochemical method, leading to the attainment of α‐Al2O3 at temperatures below 800°C. The resultant α‐Al2O3 was in the form of thin flakes, with significantly increased specific surface areas up to 27.9 m2/g. Upon characterizing the precursors post‐ball milling, a large amount of pentacoordinate aluminum was observed. The pentacoordinate aluminum has activated the alumina lattice and increased the phase transition rate, a key factor in the low temperature preparation of α‐Al2O3. This innovative approach not only simplifies the preparation process but also enables the production of high‐purity, large specific surface area lamellar α‐Al2O3 at lower temperatures, paving the way for more efficient and cost‐effective industrial processes.
Scintillation properties of transparent Lu‐α‐SiAlON:Ce3+ ceramics
Authors: Aminaka Kohei , Tatami Junichi , Iijima Motoyuki , Ito Akihiko , Matsumoto Shogen , Takahashi Takuma , Ohji Tatsuki
Published: April 2024

The high durability under harsh environment including high temperature, high humidity, and high radiation is required for scintillators used for decommissioning of nuclear facilities and radiation monitoring in nuclear fusion reactors. α‐SiAlON ceramics are highly potential for such scintillators because of their thermal and mechanical durability and luminescence corresponding to doped rare‐earth ion. In this study, scintillation properties of transparent Lu‐α‐SiAlON:Ce3+ ceramics were investigated for the first time. Lu‐α‐SiAlON:Ce3+ showed the scintillation responses to α‐rays and X‐rays. The α‐rays‐induced scintillation decay curve consists of two components whose decay time are 48 and 652 ns. The faster decay component most presumably results from 4f‐5d transition of Ce3+, whereas the origin of the slower one is unclear but may be defects in α‐SiAlON. The light yield of the Lu‐α‐SiAlON:Ce3+ ceramics was 1300 photons 5.5 MeV−1.
Observational pilot study of multi‐wavelength wearable light dosimetry for erythropoietic protoporphyria
Authors: Dickey Amy K. , Berkovich Jaime , Leaf Rebecca K. , Jiang Paul Y. , Lopez‐Galmiche Gisela , Rebeiz Lina , Wheeden Kristen , Kochevar Irene , Savage William , Zhao Sophia , Campisi Elizabeth , Heo Seung Y. , Trueb Jacob , LaRochelle Ethan P. M. , Rogers John , Banks Anthony , Chang Jan‐Kai
Published: April 2024

Background

Erythropoietic protoporphyria (EPP) causes painful light sensitivity, limiting quality of life. Our objective was to develop and validate a wearable light exposure device and correlate measurements with light sensitivity in EPP to predict and prevent symptoms.

Methods

A wearable light dosimeter was developed to capture light doses of UVA, blue, and red wavelengths. A prospective observational pilot study was performed in which five EPP patients wore two light dosimeters for 3 weeks, one as a watch, and one as a shirt clip.

Results

Standard deviation (SD) increases from the mean in the daily blue light dose increased the odds ratio (OR) for symptom risk more than the self‐reported outdoor time (OR 2.76 vs. 2.38) or other wavelengths, and a one SD increase from the mean in the daily blue light wristband device dose increased the OR for symptom risk more than the daily blue light shirt clip (OR 2.45 vs. 1.62). The area under the receiver operator curve for the blue light wristband dose was 0.78, suggesting 78% predictive accuracy.

Conclusion

These data demonstrate that wearable blue light dosimetry worn as a wristband is a promising method for measuring light exposure and predicting and preventing symptoms in EPP.
Influence of the fruit parts on bioactive compounds, antioxidant capacity, polyphenols, fatty acid and mineral contents of the pumpkin (Cucurbita maxima L.) fruits
Authors: Mohamed Ahmed Isam A. , AlJuhaimi Fahad , Özcan Mehmet Musa , Uslu Nurhan , Karrar Emad
Published: April 2024

In the current work, the effect of pumpkin parts on the oil content, total phenol, flavonoid, carotenoid quantities, antioxidant capacity, phenolic components, fatty acid profiles and mineral profiles of pumpkin parts was investigated. Total carotenoid and phenolic amounts of pumpkin parts were recorded to be from 36.84 (seed) and 29.92 μg g−1 (pulp) to 28.75 (pulp) and 67.68 mgGAE/100 g (peel) respectively. Also, total flavonoid quantities of the parts of pumpkin were assigned between 21.07 mg/100 g (pulp) and 220.36 mg/100 g (seed), while antioxidant activities of pumpkin samples range from 0.04 mmol kg−1 (pulp) to 0.82 mmol kg−1 (seed). Catechin and caffeic acid amounts of pumpkin parts varied from 13.25 (seed) and 77.31 mg/100 g (peel) to 4.70 (seed) and 7.60 mg/100 g (peel) respectively. The amount of catechin detected in the pumpkin peel was approximately two and five times higher than the pulp part. Resveratrol content was lowest in the pulp part of the pumpkin. Oleic and linoleic acid values of the oils ranged from 19.23% (peel) to 29.16% (seed) and from 18.15% (peel) to 51.06% (seed) respectively. Stearic, oleic and linoleic acids of pumpkin pulp oil were higher than pumpkin peel oil. Pumpkin seed oils are rich in oleic and linoleic acids. P, K, Mg, S and Fe were the dominant biogenic minerals of pumpkin parts. The most of total carotenoids and total phenols were accumulated in the peel part of the pumpkin fruit. The total flavonoid quantity of pumpkin seeds was approximately three times higher than the pumpkin peel part and ten times higher than the pulp part.