bluuebunny/crossref_metadata_2025 huggingface dataset:
Dedifferentiated Schwann cells promote perineural invasion mediated by the PACAP paracrine signalling in cervical cancer
Authors: Chen Guoqiang , Zheng Zhen , Sun Hao , You Jiahao , Chu Jing , Gao Jinghai , Qiu Lei , Liu Xiaojun
Published: October 2023

Perineural invasion (PNI) has emerged as a key pathological feature and be considered as a poor prognostic factor in cervical cancer. However, the underlying molecular mechanisms are largely unknown. Here, PNI status of 269 cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) samples were quantified by using whole‐slide diagnostic images obtained from The Cancer Genome Atlas. Integrated analyses revealed that PNI was an indicative marker of poorer disease‐free survival for CESC patients. Among the differentially expressed genes, ADCYAP1 were identified. Clinical specimens supported that high expression of PACAP (encoded by ADCYAP1) contributed to PNI in CESC. Mechanistically, PACAP, secreted from cervical cancer cells, reversed myelin differentiation of Schwann cells (SCs). Then, dedifferentiated SCs promoted PNI by producing chemokine FGF17 and by degrading extracellular matrix through secretion of Cathepsin S and MMP‐12. In conclusion, this study identified PACAP was associated with PNI in cervical cancer and suggested that tumour‐derived PACAP reversed myelin differentiation of SCs to aid PNI.
Preference of pear psyllid (Cacopsylla pyri) for specific colour inspires new application in plant protection
Authors: Czarnobai De Jorge Bruna , Meyhöfer Rainer , Jürgens Andreas , Gross Jürgen
Published: October 2023

Understanding the cues used by insects to select their hosts is essential for developing sustainable control strategies, particularly for plant disease vectors. Pear psyllids (Cacopsylla pyri) are vectors of the bacterial disease pear decline caused by ‘Candidatus Phytoplasma pyri’. Yellow sticky traps are typically used to monitor pest insects, but they are non‐specific and capture many beneficial insects, too. Against the background of improving visual traps, this research aimed to investigate the colour choice behaviour of C. pyri. Our first approach was to screen insect colour preferences by performing choice assays with different LED colour wavelengths in a small‐scale choice arena under controlled conditions. Over six LEDs tested, there was a strong significant preference of C. pyri for green 1 (532 nm) followed by green 2 (549 nm). Yellow (576 nm), orange (593 nm), red 1 (619 nm) and red 2 (633 nm) were less attractive than green. Subsequently, the trapping of pear psyllids was tested in the field using newly developed traps covered with transparent‐coloured PVC sheets with a similar wavelength of the preferred LEDs. Red and completely transparent traps have been used as control and combined in randomized blocks in a pear orchard. Field trials revealed that green traps ranging from 525 to 537 nm attracted significantly more pear psyllids than longer wavelength green (543 nm), red and transparent ones. The construction of specific green‐coloured sticky traps seems promising for improving psyllid trapping, especially during an early infestation at low population densities. Thus, these visual traps should be considered in future and integrated into psyllid monitoring as part of integrated pest management.
Orthodontic tooth extrusion to regenerate missing papilla adjacent to maxillary anterior single implants: A 2‐ to 7‐year retrospective study
Authors: Kan Joseph Y. K. , Rungcharassaeng Kitichai , Yin Shi , Kang Philip , Celenza Frank , Spear Frank , Chung Ji Yeon , Lozada Jaime L.
Published: October 2023

Introduction

Regeneration of the missing papilla adjacent to single implants in the esthetic zone has always been challenging, despite advances in vertical hard and soft tissue regeneration. Orthodontic tooth extrusion has been shown to effectively gain alveolar bone and gingival tissue. This retrospective study evaluated the effectiveness of orthodontic tooth extrusion on regenerating missing papilla between existing maxillary anterior single implant and its adjacent tooth.

Methods

Patients who underwent orthodontic tooth extrusion to regenerate missing papilla adjacent to a single implant in the esthetic zone were included in this study. The gingival phenotype, orthodontic extrusion movement, proximal bone level, dento‐implant papilla level, facial gingival level, mucogingival junction level, and keratinized tissue width, of the extruded tooth were recorded at pre‐orthodontic extrusion (T0), post‐orthodontic extrusion and retention (T1), and latest follow‐up (T2).

Results

A total of 17 maxillary single tooth had orthodontic tooth extrusion to regenerate missing papilla adjacent to 14 maxillary anterior single implants in 14 patients. After a mean follow‐up time of 48.4 months, implant success rate was 100% (14/14), with none of the orthodontically extruded teeth being extracted. After a mean extrusion and retention period of 14.3 months, a mean orthodontic extrusion movement of 4.62 ± 0.78 mm was noted with a mean proximal bone level gain of 3.54 ± 0.61 mm (77.0% efficacy), dento‐implant papilla level gain of 3.98 ± 0.81 mm (86.8% efficacy), and facial gingival tissue gain of 4.27 mm ± 0.55 mm (93.4% efficacy). A mean keratinized tissue width gain of 4.17 ± 0.49 mm with minimal mean mucogingival junction level change of 0.10 ± 0.30 mm were observed. The efficacy of orthodontic eruption movement on dento‐implant papilla gain was less in the thin (80.5%) phenotype group when compared with that in the thick (91.5%) phenotype group.

Conclusions

Within the confines of this study, orthodontic extrusion is an effective, noninvasive method in regenerating mid‐term stable proximal bone and papilla adjacent to maxillary anterior single implants.

Clinical Significance

This retrospective study presents a mid‐term result on orthodontic extrusion as a mean to regenerate dento‐implant papilla defect. The extended retention period following orthodontic extrusion showed stable and efficacious proximal bone and papilla gain.
Associations of liver dysfunction with incident dementia, cognition, and brain structure: A prospective cohort study of 431 699 adults
Authors: Gao Pei‐Yang , Ou Ya‐Nan , Wang Hui‐Fu , Wang Zhi‐Bo , Fu Yan , He Xiao‐Yu , Ma Ya‐Hui , Feng Jian‐Feng , Cheng Wei , Tan Lan , Yu Jin‐Tai
Published: October 2023

The relationship between liver dysfunction and dementia has been researched extensively but remains poorly understood. In this study, we investigate the longitudinal and cross‐sectional associations between liver function and liver diseases and risk of incident dementia, impaired cognition, and brain structure abnormalities using Cox proportion hazard model and linear regression model. 431 699 participants with a mean of 8.65 (standard deviation [SD] 2.61) years of follow‐up were included from the UK Biobank; 5542 all‐cause dementia (ACD), 2427 Alzheimer's disease (AD), and 1282 vascular dementia (VaD) cases were documented. We observed that per SD decreases in alanine transaminase (ALT; hazard ratio [HR], 0.917; PFDR <0.001) and per SD increases in aspartate aminotransferase (AST; HR, 1.048; PFDR = 0.010), AST to ALT ratio (HR, 1.195; PFDR <0.001), gamma‐glutamyl transpeptidase (GGT; HR, 1.066; PFDR <0.001), alcoholic liver disease (ALD; HR, 2.872; PFDR <0.001), and fibrosis and cirrhosis of liver (HR, 2.285; PFDR = 0.002), being significantly associated with a higher risk of incident ACD. Restricted cubic spline models identified a strong U‐shaped association between Alb and AST and incident ACD (Pnonlinear <0.05). Worse cognition was positively correlated with AST, AST to ALT ratio, direct bilirubin (DBil), and GGT; negatively correlated with ALT, Alb, and total bilirubin (TBil); and ALD and fibrosis and cirrhosis of liver (PFDR <0.05). Moreover, changes in ALT, GGT, AST to ALT ratio, and ALD were significantly associated with altered cortical and subcortical regions, including hippocampus, amygdala, thalamus, pallidum, and fusiform (PFDR <0.05). In sensitivity analysis, metabolic dysfunction‐associated steatotic liver disease (MASLD) was associated with the risk of ACD and brain subcortical changes. Our findings provide substantial evidence that liver dysfunction may be an important factor for incident dementia. Early intervention in the unhealthy liver may help prevent cognitive impairment and dementia incidence.
Who am I when I don't know who I am? The problem of personal identity in infants and elderly with cognitive disabilities
Authors: Alonso Marcos
Published: October 2023

This article addresses the problem of whether we can speak of personal identity in cases of infants or elderly with cognitive disabilities as hydrocephaly or dementia, lives that could be considered borderline in terms of personal identity because they lack certain characteristics normally considered indispensable for personal life. Taking as a reference recent discussions on personal identity, particularly the narrative theories of Hilde Lindemann, Françoise Baylis and Marya Schechtman, the article analyses in what sense, under what assumptions, and in what way such a thing could be defended. Finally, some problems and objections to these approaches are considered.
A case‐control survey study of environmental risk factors for primary hypoadrenocorticism in dogs
Authors: Treeful Amy E. , Searle Kelly M. , Carroll Dana M. , Yost Kathleen J. , Hedger Anna L. , Friedenberg Steven G.
Published: October 2023

Background

Primary hypoadrenocorticism in dogs is thought to be multifactorial with roles for both genetic and environmental factors. The contributions of environmental factors remain unexplored.

Objective

Identify environmental and lifestyle exposures associated with primary hypoadrenocorticism in 2 dog breeds with high risk of developing the disease.

Animals

Animals were not used in this study. Owners of Standard Poodles (STPDs) and Portuguese water dogs (POWDs) participated in a survey.

Methods

Retrospective case‐control study. Dog owners were invited to participate in an online survey through convenience sampling. Questions regarded the demographics, health histories, and indoor/outdoor environments in which their dogs live and play. Responses for dogs with primary hypoadrenocorticism were compared to those without the disease using univariate and multivariate logistic regression models.

Results

Five thousand forty‐seven responses (358 cases, 4689 controls) met initial inclusion criteria. Significant associations with modest effect size were found for community type, ingestion of canned food, and use of lawn fertilizer in some analysis models. Reproductive (spay/neuter) status exhibited the strongest association with high effect size across all models with adjusted odds ratio (OR) 2.5 (95% confidence interval [CI], 1.4‐4.5; P = .003) for spayed females and 6.0 (95% CI, 2.6‐13.9; P < .001) for neutered males.

Conclusions and Clinical Importance

The large effect size for reproductive status reflects its high potential clinical relevance, whereas modest effect sizes for other environmental variables suggest lower potential clinical relevance. These findings are associations and do not necessarily imply causation. Before any actionable recommendations are warranted, additional evidence regarding biological mechanisms is needed.
Novel stripe rust effector boosts the transcription of a host susceptibility factor through affecting histone modification to promote infection in wheat
Authors: Duan Wanlu , Hao Zhenkai , Pang Huihui , Peng Yuxi , Xu Yiwen , Zhang Yanfei , Zhang Ying , Kang Zhensheng , Zhao Jing
Published: October 2023

Regulation of host gene expression to promote disease is a common strategy for plant pathogens. However, it remains unclear whether or not fungal pathogens manipulate host gene expression directly through secreted effectors with transcriptional activity.

Here, we identified a fungal effector PstGTA1 from Puccinia striiformis f. sp. tritici (Pst), which has partial homology to the subunit of global transcriptional activator SNF2 from oyster. The transcriptional activating activity of PstGTA1 was validated in yeast, and the potential role of PstGTA1 in pathogenicity was assessed using gene silenced and overexpression transgenic wheat plants. Candidate targets regulated by PstGTA1 were screened by transcriptomic analysis, and the specific promoter region binding to PstGTA1 was further determined.

PstGTA1 can be delivered to the wheat cell nucleus and contributes to the full virulence of Pst by targeting the promoter of TaSIG, a gene negatively regulating wheat immunity, and possibly activates its transcription by affecting the histone H3K4 acetylation level.

Our study provides the first direct evidence for a fungal effector with transactivation activity modulating the transcription of a host specific susceptibility gene through promoter binding and histone acetylation.
Support for unconditional basic income in Spain: A materialist or post‐materialist issue?
Authors: Guerendiain‐Gabás Itziar , Gil de Montes Lorena , Bobowik Magdalena , Arnoso‐Martínez Maitane
Published: October 2023

Unconditional basic income (UBI) is a redistributive policy proposal that is receiving increasing attention in the Spanish political sphere. Welfare attitudes literature has shown that support for UBI is higher among left‐wing citizens and those of lower socioeconomic status. However, previous studies have not addressed the mediating role of ideological values such as egalitarianism or meritocratism in supporting UBI. Furthermore, studies have not considered the interactive relationship between ideological and self‐interest motives when studying attitudes toward UBI. Drawing on modernization theory, we propose that individuals' socioeconomic status conditions the role of ideological motivations in shaping support for UBI. To test this hypothesis, we study data from two different surveys conducted in Spain in 2017 (N = 1958) and 2021 (N = 2004). Our findings suggest that ideology is a less relevant motivation for supporting UBI among the Spanish citizens of lower socioeconomic status, but it becomes increasingly salient among higher‐status citizens. Among the latter, egalitarian values lead leftists to support UBI, whereas anti‐egalitarian and meritocratic values lead rightists to anti‐UBI positions. We discuss these findings within the framework of modernization theory, addressing support for UBI by different social groups and the ability of this policy proposal to elicit broad‐based support.
Salicylate and jasmonate intertwine in ROS‐triggered chloroplast‐to‐nucleus retrograde signaling
Authors: Bali Shagun , Gautam Ayushi , Dhiman Aarzoo , Michael Rahul , Dogra Vivek
Published: October 2023

Plants, being sessile, are frequently exposed to environmental perturbations, affecting their sustenance and survival. In response, distinct inherent mechanisms emerged during plant evolution to deal with environmental stresses. Among various organelles, chloroplast plays an indispensable role in plant cells. Besides providing the site for photosynthesis and biosynthesis of many important primary and secondary metabolites, including hormones, chloroplasts also act as environmental sensors. Any environmental perturbation directly influences the photosynthetic electron transport chain, leading to excess accumulation of reactive oxygen species (ROS), causing oxidative damages to biomolecules in the vicinity. To prevent excess ROS accumulation and the consequent oxidative damages, the chloroplast activates retrograde signaling (RS) pathways to reprogramme nuclear gene expression, defining plant's response to stress. Based on levels and site of ROS accumulation, distinct biomolecules are oxidized, generating specific derivatives that act as genuine signaling molecules, triggering specific RS pathways to instigate distinctive responses, including growth inhibition, acclimation, and programmed cell death. Though various RS pathways independently modulate nuclear gene expression, they also implicate the defense hormone salicylic acid (SA) and oxylipins, including 12‐oxo‐phytodienoic acid (OPDA) and jasmonic acid (JA), by promoting their biosynthesis and utilizing them for intra‐ and intercellular communications. Several studies reported the involvement of both hormones in individual RS pathways, but the precise dissection of their activation and participation in a given RS pathway remains an enigma. The present review describes the current understanding of how SA and JA intertwine in ROS‐triggered RS pathways. We have also emphasized the future perspectives for elucidating stress specificity and spatiotemporal accumulation of respective hormones in a given RS pathway.
Collegiate Sports Participation, Academic Achievement, and Bachelor's Degree Completion1
Authors: Tompsett James , Mcdossi Oded , Roscigno Vincent J.
Published: October 2023

Popular attention to the multi‐million‐dollar enterprise of collegiate sports often centers on the extent to which student athletes are academically engaged. In this article, we draw on a national sample of approximately 5,000 college‐goers, employ key comparisons (i.e., high‐visibility student athletes, nonrevenue student athletes, and nonathletes), and consider background disadvantages and collegiate division levels relative to achievement (i.e., grade point average) and bachelor's degree completion. Analyses show that once background attributes and division levels are accounted for, there is little difference in achievement and attainment between high‐visibility student athletes and their nonathlete peers. There is, however, a dual advantage in 4‐year degree completion for those playing other collegiate sports—an advantage tied to their more privileged family and educational backgrounds and their participation in intercollegiate athletics itself. Our results in these regards are robust to several restrictive and analytically rigorous modeling strategies. We conclude by highlighting the implications for higher education research and its attention to inequality, educational representation, institutional processes, and student success.
Linking rifted margin crustal shape with the timing and volume of magmatism
Authors: Chenin Pauline , Tomasi Simon , Kusznir Nick , Manatschal Gianreto
Published: October 2023

Determining the volume and timing of magmatism during rifting and breakup is challenging due to the similar density and seismic velocity of inherited continental crust, magmatic additions and serpentinized mantle; and the difficulty of dating magmatic additions. Here rules of thumb to estimate these are proposed based on the characteristics of the top basement and Moho on seismically imaged margins. A simple kinematic model is used to generate first‐order crustal shapes of margins as a function of magma volume and timing of emplacement, which are successfully compared to a representative number of rifted margins. It appears that ‘magma‐rich margins’ require melt emplacement in advance of crustal thinning but not necessarily enhanced melt volume, while margins with exhumed mantle require a delay in melt emplacement but not necessarily a low magmatic volume. An alternative classification for the magma‐poor/magma‐rich dichotomy is proposed to better represent the crustal shape variability of rifted margins.
Cytomegalovirus‐driven early‐onset lymphocytosis in hematopoietic allogeneic transplant mimicking a T‐cell lymphoma progression
Authors: Eirís Juan , Aguilar Cristóbal , Guerreiro Manuel
Published: October 2023

Hepatosplenic T‐cell lymphoma (HSTCL) is an uncommon and highly aggressive subtype of peripheral T‐cell lymphoma characterized by liver, spleen, and bone marrow involvement. Allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative treatment for HSTCL, but it carries a significant risk of relapse. Cytomegalovirus (CMV) reactivation is a frequent complication after alloHSCT, particularly in patients undergoing lymphocyte‐toxic therapies. A 27‐year‐old man diagnosed with HSTCL underwent an alloHSCT with active disease after six lines of therapy. A CMV reactivation was successfully treated with foscarnet. A sudden reappearance of symptomatic lymphocytosis (15,550/μL) by day +20, prior to engraftment, raised suspicion of disease progression. A comprehensive diagnostic work‐up revealed an oligoclonal expansion of donor lymphocytes along with complete donor chimerism, leading to an alternative diagnosis of a CMV‐driven T‐cell expansion. This was confirmed by an in vitro assay testing T‐cell specificity against CMV. The patient achieved both complete response and complete donor chimerism despite persisting lymphocytosis, but ultimately relapsed. This case highlights the importance of diagnostic tools in understanding disease progression and guiding treatment decisions.
Spatiotemporal single-cell tracking analysis in 3D tissues to reveal heterogeneous cellular response to mechanical stimuli
Authors: Kasahara Keitaro , Muramatsu Jumpei , Kurashina Yuta , Miura Shigenori , Miyata Shogo , Onoe Hiroaki
Published: October 2023

Mechanical stimuli have been recognized as important for tissue maturation, homeostasis and constructing engineered three-dimensional (3D) tissues. However, we know little about the cellular mechanical response in tissues that could be considerably heterogeneous and spatiotemporally dynamic due to the complex structure of tissues. Here, we report a spatiotemporal single-cell tracking analysis of in vitro 3D tissues under mechanical stretch, to reveal the heterogeneous cellular behavior by using a developed stretch and optical live imaging system. The system could affect the cellular orientation and directly measure the distance of cells in in vitro 3D myoblast tissues (3DMTs) at the single-cell level. Moreover, we observed the spatiotemporal heterogeneous cellular locomotion and shape changes under mechanical stretch in 3DMTs. This single-cell tracking analysis can become a principal method to investigate the heterogeneous cellular response in tissues and provide insights that conventional analyses have not yet offered.
Mechanistic insights into the enzymatic activity of E3 ligase HOIL-1L and its regulation by the linear ubiquitin chain binding
Authors: Xu Xiaolong , Wang Yaru , Zhang Yan , Wang Yingli , Yin Yue , Peng Chao , Gong Xinyu , Li Miao , Zhang Yuchao , Zhang Mingfang , Tang Yubin , Zhou Xindi , Liu Haobo , Pan Lifeng
Published: October 2023

Heme-oxidized IRP2 ubiquitin ligase 1 (HOIL-1L) serves as a unique E3 ligase to catalyze the mono-ubiquitination of relevant protein or sugar substrates and plays vital roles in numerous cellular processes in mammals. However, the molecular mechanism underpinning the E3 activity of HOIL-1L and the related regulatory mechanism remain elusive. Here, we report the crystal structure of the catalytic core region of HOIL-1L and unveil the key catalytic triad residues of HOIL-1L. Moreover, we discover that HOIL-1L contains two distinct linear di-ubiquitin binding sites that can synergistically bind to linear tetra-ubiquitin, and the binding of HOIL-1L with linear tetra-ubiquitin can promote its E3 activity. The determined HOIL-1L/linear tetra-ubiquitin complex structure not only elucidates the detailed binding mechanism of HOIL-1L with linear tetra-ubiquitin but also uncovers a unique allosteric ubiquitin-binding site for the activation of HOIL-1L. In all, our findings provide mechanistic insights into the E3 activity of HOIL-1L and its regulation by the linear ubiquitin chain binding.
Draft genome sequence of
Enterobacter hormaechei
DVZ29, an iodide-oxidizing bacterium isolated from the Hanford site
Authors: Robinson Courtney J. , Smith Robert L. , Howard M. Hope , Saunders Danielle L. , Lee Brady D.
Published: October 2023

Enterobacter hormaechei
DVZ29 was isolated from a sediment trap incubated in an
129
I plume at the Hanford Site (Washington State, USA). A whole genome sequencing of the strain resulted in 32 contigs and revealed that the genome is 4.90 Mb, with a G + C content of 55.61%.
XanFur, a novel Fur protein induced by H
2
O
2
, positively regulated by the global transcriptional regulator Clp and required for the full virulence of
Xanthomonas oryzae
pv.
oryzae
in rice
Authors: Zhang Yu-Qiang , Song Xiao-Yan , Liu Fengquan
Published: October 2023

Bacterial leaf blight caused by
Xanthomonas oryzae
pv.
oryzae
(
Xoo
) is one of the most destructive diseases in rice. However, the pathogenic mechanisms of
Xoo
have not been fully understood. In this study, we identified a novel ferric uptake regulator (Fur) protein, XanFur, in
Xoo,
which is conserved among the major pathogens of
Xanthomonas
species, but has no obvious sequence identity with reported Fur proteins. Gene deletion indicated that
xanfur
is required for the full virulence of
Xoo
in rice. The expression of
xanfur
was significantly induced by 0.1 mM H
2
O
2
and its deletion caused a significant decrease in the tolerance of
Xoo
to H
2
O
2
, suggesting that
xanfur
is likely involved in the resistance of
Xoo
to the oxidative stress caused by H
2
O
2
in rice. The loss of
xanfur
also caused significant reduction in extracellular polysaccharide production, biofilm formation, and cell motility, suggesting that
xanfur
may be also involved in regulating these virulence determinants of
Xoo
. Furthermore, both
in vivo
and
in vitro
experimental results demonstrated that the global transcriptional regulator Clp positively regulated the expression of
xanfur
by directly binding to its promoter region, especially in the presence of 0.1 mM H
2
O
2
, presenting the cellular regulatory pathway for the expression of this gene. These results not only contribute to a better understanding of the interaction mechanisms between rice and
Xoo
, but also provide reference to developing high-effective bactericides by targeting to the Fur protein in
Xoo
to control bacterial leaf blight in rice.

IMPORTANCE

Although
Xanthomonas oryzae
pv.
oryzae
(
Xoo
) has been found to be a bacterial pathogen causing bacterial leaf blight in rice for many years, the molecular mechanisms of the rice-
Xoo
interaction has not been fully understood. In this study, we found that XanFur of
Xoo
is a novel ferric uptake regulator (Fur) protein conserved among major pathogenic
Xanthomonas
species. XanFur is required for the virulence of
Xoo
in rice, and likely involved in regulating the virulence determinants of
Xoo
. The expression of
xanfur
is induced by H
2
O
2
, and positively regulated by the global transcriptional regulator Clp. Our results reveal the function and regulation of the novel virulence-related Fur protein XanFur in
Xoo,
providing new insights into the interaction mechanisms of rice-
Xoo
.
Infantile inflammatory myofibroblastic tumour of the sigmoid colon: a diagnostic dilemma
Authors: Kavirayani Vaishnavi , Pai Nitin G , Nayal Bhavna , Prabhu Santosh
Published: October 2023

An inflammatory myofibroblastic tumour (IMT) is an uncommon neoplasm composed of inflammatory cells and myofibroblasts in a fibrous stroma. They are mostly seen in the lungs and rarely involve the gastrointestinal tract. An 8-month-old infant presented with a history of lower abdominal lump for 2 months. Her CT scan confirmed a large, lobulated mass in the retroperitoneum arising from the pelvis. The mass was found to be arising from the sigmoid colon on laparotomy which was excised. Histopathology showed a cellular tumour composed of spindle cells and inflammatory lymphocytic infiltrate. Immunohistochemistry revealed positive staining for anaplastic lymphoma kinase and smooth muscle actin, confirming the diagnosis of IMT. The patient is doing well at her 6-month follow-up. Ours is the youngest case of sigmoid IMT among the only other series of eight cases reported in the literature indicating its rarity.
Antiasthmatic prescriptions in children with and without congenital anomalies: a population-based study
Authors: Divin Natalie , Given Joanne Emma , Tan Joachim , Astolfi Gianni , Ballardini Elisa , Barrachina-Bonet Laia , Cavero-Carbonell Clara , Coi Alessio , Garne Ester , Gissler Mika , Heino Anna , Jordan Susan , Pierini Anna , Scanlon Ieuan , Urhøj Stine Kjær , Morris Joan K , Loane Maria
Published: October 2023

Objectives

To explore the risk of being prescribed/dispensed medications for respiratory symptoms and breathing difficulties in children with and without congenital anomalies.

Design

A EUROlinkCAT population-based data linkage cohort study. Data on children with and without congenital anomalies were linked to prescription databases to identify children who did/did not receive antiasthmatic prescriptions. Data were analysed by age, European region, class of antiasthmatic, anomaly, sex, gestational age and birth cohort.

Setting

Children born 2000–2014 in six regions within five European countries.

Participants

60 662 children with congenital anomalies and 1 722 912 reference children up to age 10 years.

Primary outcome measure

Relative risks (RR) of >1 antiasthmatic prescription in a year, identified using Anatomical Therapeutic Chemical classification codes beginning with R03.

Results

There were significant differences in the prescribing of antiasthmatics in the six regions. Children with congenital anomalies had a significantly higher risk of being prescribed antiasthmatics (RR 1.41, 95% CI 1.35 to 1.48) compared with reference children. The increased risk was consistent across all regions and all age groups. Children with congenital anomalies were more likely to be prescribed beta-2 agonists (RR 1.71, 95% CI 1.60 to 1.83) and inhaled corticosteroids (RR 1.74, 95% CI 1.61 to 1.87). Children with oesophageal atresia, genetic syndromes and chromosomal anomalies had over twice the risk of being prescribed antiasthmatics compared with reference children. Children with congenital anomalies born <32 weeks gestational age were over twice as likely to be prescribed antiasthmatics than those born at term (RR 2.20, 95% CI 2.10 to 2.30).

Conclusion

This study documents the additional burden of respiratory symptoms and breathing difficulties for children with congenital anomalies, particularly those born preterm, compared with children without congenital anomalies in the first 10 years of life. These findings are beneficial to clinicians and healthcare providers as they identify children with greater morbidity associated with respiratory symptoms, as indicated by antiasthmatic prescriptions.
Protocol for a randomised, multicentre, four-arm, double-blinded, placebo-controlled trial to assess the benefits and safety of iron supplementation with malaria chemoprevention to children in Malawi: IRMA trial
Authors: Mwangi Martin N. , Mzembe Glory , Ngwira Chikondi C. , Vokhiwa Maclean , Kapulula Mayamiko D. , Larson Leila M. , Braat Sabine , Harding Rebecca , McLean Alistair R. D. , Hamadani Jena D. , Biggs Beverley-Ann , Ataíde Ricardo , Phiri Kamija S. , Pasricha Sant-Rayn
Published: October 2023

Introduction

Approximately 40% of children aged 6–59 months worldwide are anaemic. Iron-containing multiple micronutrient powders (MNPs) and iron supplements (syrup/drops) are used to combat anaemia in children in different parts of the world. However, evidence for functional benefits of iron supplementation in children is scarce, and potential risks remain poorly defined, particularly concerning diarrhoea and malaria. This trial aims to determine if: (1) the efficacy of iron supplements or MNPs (containing iron) given with malaria chemoprevention is superior to malaria chemoprevention alone, or (2) if the efficacy of malaria chemoprevention alone is superior to placebo on child cognitive development.

Methods and analysis

IRMA is a four-arm, parallel-group, double-blinded, placebo-controlled, triple-dummy, randomised trial in Southern Malawi. The study recruits 2168 infants aged 6 months, with an intervention period of 6 months and a post-intervention period of a further 6 months. Children are randomised into four arms: (1) No intervention (placebo); (2) malaria chemoprevention only; (3) MNPs and malaria chemoprevention; and (4) iron syrup and malaria chemoprevention. The primary outcome, cognitive development (Cognitive Composite Score (CogCS)), is measured at the end of the 6 months intervention. Secondary outcomes include CogCS at a further 6 months post-intervention, motor, language and behavioural development, physical growth and prevalence of anaemia and iron deficiency. Safety outcomes include incidence of malaria and other infections, and prevalence of malaria parasitaemia during and post-intervention period.

Ethics and dissemination

The trial is approved by the National Health Sciences Research Committee (#19/01/2213) (Malawi) and the Human Research Ethics Committee (WEHI: 19/012) (Australia). Written informed consent in the local language is obtained from each participant before conducting any study-related procedure. Results will be shared with the local community and internationally with academic and policy stakeholders.

Trial registration number

ACTRN12620000386932.
Predictive value of perioperative procalcitonin, C reactive protein and high-sensitivity C reactive protein for the risk of postoperative complications after non-cardiac surgery in elderly patients: a nested case–control study
Authors: Chen Yali , Zhao Yi , Liu Juan , Teng Yi , Ou Mengchan , Hao Xuechao
Published: October 2023

Objective

Little is known about the correlation between perioperative concentrations of inflammatory biomarkers and postoperative complications. This study explored whether the plasma concentrations and perioperative changes of procalcitonin (PCT), C reactive protein (CRP) and high-sensitivity CRP (hsCRP) could predict the risk of postoperative morbidity in elderly patients undergoing elective non-cardiac surgery.

Design

A nested case–control study.

Setting

A tertiary hospital in China.

Participants

A total of 498 patients aged ≥65 years from a prospective cohort who underwent elective non-cardiac surgery between June 2020 and April 2021.

Primary outcome measures

The primary outcomes were the efficacy of plasma concentrations of PCT, CRP and hsCRP in predicting the risk of Clavien-Dindo Classification (CDC) ≥grade 3 and major complications. The major complications included mortality, an intensive care unit stay length >24 hour, cardiovascular events, acute kidney injury, postoperative cognitive dysfunction and infections.

Results

For major complications, the area under the curve (AUC) (95% CI) of PCT-24 hours, PCT change and PCT change rate were 0.750 (0.698 to 0.803), 0.740 (0.686 to 0.795) and 0.711 (0.651 to 0.771), respectively. The AUC (95% CI) of CRP-24 hours, CRP change, CRP change rate and hsCRP baseline were 0.835 (0.789 to 0.881), 0.818 (0.770 to 0.867), 0.691 (0.625 to 0.756) and 0.616 (0.554 to 0.678), respectively. For complications ≥CDC grade 3, the AUC (95% CI) of PCT-24 hours, PCT change and PCT change rate were 0.662 (0.543 to 0.780), 0.643 (0.514 to 0.772) and 0.627 (0.494 to 0.761), respectively. The AUC (95% CI) of CRP-24 hours and hsCRP baseline were 0.649 (0.527 to 0.771) and 0.639 (0.530 to 0.748), respectively.

Conclusions

PCT-24 hours, CRP-24 hours, the change of perioperative PCT and CRP were valuable predictors of major complications occurring within 30 days after non-cardiac surgery in the elderly.

Trial registration number

China Clinical Trial Registry: ChiCTR1900026223.
Cocreators’ experiences and effectiveness of cocreated interventions in improving health behaviours of adults with non-communicable diseases: a systematic review protocol
Authors: Anieto Ebuka Miracle , Abaraogu Ukachukwu , Dall Philippa Margaret , Anieto Ijeoma Blessing , Ogbueche Chukwudi Martin , Seenan Chris
Published: October 2023

Introduction

Improved health behaviours and help-seeking behaviour reduce morbidity and mortality from non-communicable diseases (NCDs). Compliance with the recommendations of lifestyle changes for the management of NCDs has been challenging, as patients find it difficult to change and sustain lifestyle behaviours for a long period of time. Studies have reported that cocreated interventions are promising in addressing negative health behaviours and improving health outcomes in people with NCDs; however, no conclusive evidence exists. Therefore, this review aims to evaluate cocreators’ experiences and the effectiveness of cocreated interventions in improving the health behaviours of individuals with NCDs.

Methods and analysis

This review will follow the recommendations described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline and the Enhancing Transparency in Reporting the Synthesis of Qualitative Research statement for the synthesis of qualitative data. The following databases: Co-creation Database (https://zenodo.org/record/6773028%23.Y9h2sezP1pg), MEDLINE (via OVID), Cumulative Index to Nursing and Allied Health Literature (via EBSCO Host), EMBASE (via OVID), PsycINFO (via OVID), Scopus, Web of Science, Cochrane Library and grey literature will be searched. The identified studies will be independently screened by two reviewers to determine their eligibility. The review will target to include studies that investigated the experiences of cocreators and/or the effectiveness of cocreated interventions on the health behaviour and/or health outcomes of adults with NCDs. Two independent reviewers will also appraise the quality of the included studies, as well as data extraction. A narrative synthesis will be used to summarise the findings. Thematic synthesis and meta-analysis will be conducted for the qualitative and quantitative data, respectively. The qualitative and quantitative findings will be integrated using the parallel result convergent synthesis.

Ethics and dissemination

Ethics approval is not applicable because the review will only use data from the published studies. The findings will be disseminated through publication in peer-reviewed journals and conference presentations.

PROSPERO registration number

CRD42023391746.
PAllidal versus SubThalamic deep brain Stimulation for Cervical Dystonia (PASTS-CD): study protocol for a multicentre randomised controlled trial
Authors: Liu Bin , Xu Junpeng , Yang Haonan , Yu Xinguang , Mao Zhiqi
Published: October 2023

Introduction

Deep brain stimulation (DBS) has been validated as a safe and effective treatment for refractory cervical dystonia (CD). Globus pallidus internus (GPi) and subthalamic nucleus (STN) are the two main stimulating targets. However, there has been no prospective study to clarify which target is the better DBS candidate for CD. The objective of this trial is to compare directly the efficacy and safety of GPi-DBS and STN-DBS, thereby instructing the selection of DBS target in clinical practice.

Methods and analysis

This multicentre, prospective, randomised, controlled study plans to enrol 98 refractory CD patients. Eligible CD patients will be randomly allocated to GPi-DBS group or STN-DBS group, with the DBS electrodes implanted into the posteroventral portion of GPi or the dorsolateral portion of STN, respectively. The primary outcome will be the improvement of symptomatic severity, measured by the changes in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale and the Tsui scale at 3 months, 6 months and 12 months after surgery. The secondary outcomes include the improvement of the TWSTRS-disability subscale, TWSTRS-pain subscale, quality of life, mental and cognitive condition, as well as the differences in stimulation parameters and adverse effects. In addition, this study intends to identify certain predictors of DBS efficacy for CD.

Ethics and dissemination

The trial has been approved by the Medical Ethics Committee of Chinese PLA General Hospital (S2022-613-01). The results of this study will be published in international peer-reviewed journals and shared in professional medical conferences.

Trial registration number

NCT05715138.
Demographic, social and geographic factors associated with glycaemic control among US Veterans with new onset type 2 diabetes: a retrospective cohort study
Authors: Lee David C , Orstad Stephanie L , Kanchi Rania , Adhikari Samrachana , Rummo Pasquale E , Titus Andrea R , Aleman Jose O , Elbel Brian , Thorpe Lorna E , Schwartz Mark D
Published: October 2023

Objectives

This study evaluated whether a range of demographic, social and geographic factors had an influence on glycaemic control longitudinally after an initial diagnosis of diabetes.

Design, setting and participants

We used the US Veterans Administration Diabetes Risk national cohort to track glycaemic control among patients 20–79-year old with a new diagnosis of type 2 diabetes.

Primary outcome and methods

We modelled associations between glycaemic control at follow-up clinical assessments and geographic factors including neighbourhood race/ethnicity, socioeconomic, land use and food environment measures. We also adjusted for individual demographics, comorbidities, haemoglobin A1c (HbA1c) at diagnosis and duration of follow-up. These factors were analysed within strata of community type: high-density urban, low-density urban, suburban/small town and rural areas.

Results

We analysed 246 079 Veterans who developed a new type 2 diabetes diagnosis in 2008–2018 and had at least 2 years of follow-up data available. Across all community types, we found that lower baseline HbA1c and female sex were strongly associated with a higher likelihood of within-range HbA1c at follow-up. Surprisingly, patients who were older or had more documented comorbidities were more likely to have within-range follow-up HbA1c results. While there was variation by community type, none of the geographic measures analysed consistently demonstrated significant associations with glycaemic control across all community types.
Enhancing hydraulic fracturing for in-situ remediation in low-permeability soils: A comprehensive investigation of fracture propagation
Authors: Cui Zhuang , Hou Bing
Published: October 2023

Enhancing the complexity of the hydraulic fractures to provide a wide channel for the injection of the agent is crucial for remediating low-permeability contaminated sites. This study involved a physical simulation experiment of large-scale true triaxial hydraulic fracturing in undisturbed soil, as well as field fracturing tests, to investigate fracture initiation mechanisms and the influence of different factors on fracture propagation. The study revealed a unique failure mode for low-permeability soils characterized by impact splitting, involving simultaneous tensile and shear failure. Three typical fracture propagation patterns emerged: (1) horizontal fracture, (2) parallel fracture, and (3) complex fracture. Silty clay predominantly exhibited horizontal fractures, while mucky clay facilitated the formation of complex fractures dominated by multiple transverse fractures. As the vertical stress difference coefficient increased from 1.0 to 1.5, the pressure on the fracture surface enhanced the connection between hydraulic fractures and natural fractures. Hydraulic fracturing in low-permeability soils necessitated large displacements and high-viscosity fracturing fluids to sustain fracture propagation. The field fracturing test results underscored that soil type and in-situ stress were the primary factors governing hydraulic fracture initiation and propagation. Identifying the optimal fracturing location was critical for achieving the maximum stimulated formation volume.
Analysis of the mechanism of the effect of N–H–O impurities on diamond growth under HPHT
Authors: Cai Zhenghao , Wang Zhiwen , Zhao Hongyu , Li Ming , Li Bowei , Chen Liangchao , Ma Hongan , Jia Xiaopeng
Published: October 2023

In this work, diamond crystals were synthesized with N–H–O impurities by the temperature gradient method (TGM) under high pressure and high temperature (HPHT) conditions using FeNi alloy as the metal solvent (MS). The results indicated that the spontaneous nucleation rate and proportion, growth characteristics, surface growth texture, and the impurity concentration of diamond crystals changed drastically upon changing the impurity content in the system. Mutual diffusion between the MS and carbon source (CS) was also blocked, which seriously inhibited the growth rate of diamond crystals. X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) analyses corroborated that the zero-valent iron (Fe0) and nickel (Ni0) contents declined after N–H–O impurities were introduced. The newly formed graphite can be found in the MS, but the ferric carbide disappears. XPS also confirmed shifts in the binding energy of FeNi MS peaks, more iron oxide and nickel oxide were identified in MS, hindering the mass transfer process. CO and NO were absorbed on the surface of MS, which hindered the surface processes of diamond growth. The formation of intermediates (Fe3C) was impeded during diamond growth and blocked the spontaneous nucleation of diamond. All of these phenomena contributed to a poor growth rate and changed the surface growth process of diamond crystals.
T-Distributed Stochastic Neighbor Embedding for Co-Representation Learning
Authors: Chen Wei , Wang Hongjun , Zhang Yinghui , Deng Ping , Luo Zhipeng , Li Tianrui
Published: October 2023

Co-clustering is the simultaneous clustering of the samples and attributes of a data matrix that provides deeper insight into data than traditional clustering. However, there is a lack of representation learning algorithms that serve this mechanism of co-clustering, and the current representation learning algorithms are limited to the sample perspective and lack the use of information in the attribute perspective. To solve this problem, in this article,
ctSNE
, a co-representation learning model based on t-distributed stochastic neighbor embedding, is proposed for unsupervised co-clustering, where ctSNE makes the dataset representation outputted more discriminative of row and column clusters (i.e. co-discrimination). On the basis of t-distributed stochastic neighbor embedding retaining the sample data distribution and local data structure, the philosophy of collaboration is introduced (i.e., row and column hidden relationship information) so that the ctSNE model is equipped with co-representation learning capability, which can effectively improve the performance of co-clustering. To prove the effectiveness of the ctSNE model, several classic co-clustering algorithms are used to check the co-representation performance of ctSNE, and a novel internal index based on an internal clustering index, known as total inertia, is proposed to demonstrate the effect of co-clustering. The numerous experimental results show that ctSNE has tremendous co-representation capability and can significantly improve the performance of co-clustering algorithms.
Within-Host Evolution of Bacterial Pathogens in Acute and Chronic Infection
Authors: Dekker John P.
Published: October 2023

Bacterial pathogens undergo remarkable adaptive change in response to the selective forces they encounter during host colonization and infection. Studies performed over the past few decades have demonstrated that many general evolutionary processes can be discerned during the course of host adaptation, including genetic diversification of lineages, clonal succession events, convergent evolution, and balanced fitness trade-offs. In some cases, elevated mutation rates resulting from mismatch repair or proofreading deficiencies accelerate evolution, and active mobile genetic elements or phages may facilitate genome plasticity. The host immune response provides another critical component of the fitness landscapes guiding adaptation, and selection operating on pathogens at this level may lead to immune evasion and the establishment of chronic infection. This review summarizes recent advances in this field, with a special focus on different forms of bacterial genome plasticity in the context of infection, and considers clinical consequences of adaptive changes for the host.