bluuebunny/crossref_metadata_2025 huggingface dataset:
Natural killer cells and engagers: Powerful weapons against cancer
Authors: Bottino Cristina , Picant Valentin , Vivier Eric , Castriconi Roberta
Published: August 2024

Natural killer (NK) cells are innate immune effectors whose functions rely on receptors binding cytokines, recognizing self‐molecules, or detecting danger signals expressed by virus‐infected or tumor cells. The potent cytotoxic potential makes NK cells promising candidates for cancer immunotherapy. To enhance their activity strategies include cytokine administration, blocking of immune checkpoints, and designing of antibody‐based NK cell engagers (NKCEs). NKCEs represent a cutting‐edge approach to cancer therapy: they strengthen the NK‐to‐target cell interactions and optimize tumor killing, possibly overcoming the immunosuppressive tumor microenvironment. NK cells belong to the innate lymphoid cells (ILCs) and are categorized into different subsets also including cells with a memory‐like phenotype: this complexity needs to be explored in the context of cancer immunotherapy, particularly when designing NKCEs. Two strategies to enhance NK cell activity in cancer patients can be adopted: activating patients' own NK cells versus the adoptive transfer of ex vivo activated NK cells. Furthermore, the capability of NKCEs to activate γδ T cells could have a significant synergistic effect in immunotherapy.
The function of antibodies
Authors: Daëron Marc
Published: August 2024

Antibodies have multiple biological activities. They can both recognize and act on specific antigens. They can protect against and cause serious diseases, enhance and inhibit antibody responses, enable survival, and threaten life. Which among their many, often antagonistic properties explains that antibodies were selected half a billion years ago and transmitted to mammals across millions of generations? In other words, what is the function of antibodies? Here I examine how their structure endows antibodies with unique cognitive and effector properties that contribute to their multiple biological activities. I show that rather than specific properties, antibodies have large functional repertoires. They have a cognitive repertoire and an effector repertoire that are selected from larger available repertoires, themselves drawn at random from even larger virtual repertoires. These virtual repertoires provide the adaptive immune system with immense, constantly renewed, reservoirs of cognitive and effector functions that can be actualized at any time according to the context. I propose that such a flexibility, which enables living individuals to adapt to a rapidly changing environment, and even deal with an unknown future, may provide a better selective advantage than any particular function.
National Humiliation: Emotion, Narrative, and Conflict
Authors: Majeed Raamy
Published: August 2024

National humiliation is increasingly being used as a way of explaining certain kinds of international conflict. In this article, I argue that while such explanations are presented on the back of plausible assumptions about emotion, such assumptions also make it unlikely that humiliation can play the myriad of explanatory roles attributed to it, for example, to explain the rise of Hitler, growing Chinese antagonism towards the West, Russia's invasion of Ukraine, and so on. In response, I consider some other ways humiliation may play a role in international conflict and argue that what are likely to be most relevant are not humiliating experiences, felt by individuals or groups, but rather humiliation narratives, which are often used as a discursive mechanism to justify conflict. This is important because it means a nation's willingness to engage in international conflict depends not on something which seems intractable (that is, the emotions felt by its citizens), but something more malleable: the narratives it accepts as frames for historical events.
A novel KCND3 variant in the N‐terminus impairs the ionic current of Kv4.3 and is associated with SCA19/22
Authors: Reis Marlen Colleen , Mandler Laura , Kang Jun‐Suk , Oliver Dominik , Halaszovich Christian , Nolte Dagmar
Published: August 2024

Spinocerebellar ataxias (SCAs) are a genetically heterogeneous group of autosomal dominant movement disorders. Among the SCAs associated with impaired ion channel function, SCA19/22 is caused by pathogenic variants in KCND3, which encodes the voltage‐gated potassium channel Kv4.3. SCA19/22 is clinically characterized by ataxia, dysarthria and oculomotor dysfunction in combination with other signs and symptoms, including mild cognitive impairment, peripheral neuropathy and pyramidal signs. The known KCND3 pathogenic variants are localized either in the transmembrane segments, the connecting loops, or the C‐terminal region of Kv4.3. We have identified a novel pathogenic variant, c.455A>G (p.D152G), localized in the N‐terminus of Kv4.3. It is located in the immediate neighbourhood of the T1 domain, which is responsible for multimerization with the β‐subunit KChIP2b and thus for the formation of functional heterooctamers. Electrophysiological studies showed that p.D152G does not affect channel gating, but reduces the ionic current in Kv4.3, even though the variant is not located in the transmembrane domains. Impaired channel trafficking to the plasma membrane may contribute to this effect. In a patient with a clinical picture corresponding to SCA19/22, p.D152G is the first pathogenic variant in the N‐terminus of Kv4.3 to be described to date with an effect on ion channel activity.
Simultaneous effective monitoring of Grapholita molesta and Cydia pomonella (Lepidoptera: Tortricidae) in traps with a dual sex pheromone/kairomone lure plus a UV‐A light
Authors: Knight Alan Lee , Mujica Valentina , Basoalto Esteban , Preti Michele
Published: August 2024

Studies of oriental fruit moth (OFM), Grapholita molesta (Busck), and codling moth (CM), Cydia pomonella (L.) (Lepidoptera: Tortricidae), both important pests of pome fruit, evaluated the addition of low‐intensity light‐emitting diode (LED) to delta traps baited with 3 commercial monitoring lures. Studies were conducted in 9 orchards treated with and without sex pheromone mating disruption for one or both species. OFM was monitored with a two‐part pheromone/kairomone lure (OFM Combo Dual), while CM was monitored with either a two‐part kairomone lure (CM Dual 4 K) or a sex pheromone lure (CM PH). Both pests were monitored with or without the addition of three types of a low power LED light with peak intensity at 395 (UV‐A), 458 (blue), and 516 (green) nm. The UV‐A LED was found to be the most effective among the three lights for OFM. Unexpectedly, traps with the OFM Combo Dual lure plus UV‐A LED caught similar numbers of CM as traps baited with the CM Dual 4 K and CM PH lures alone. They also caught other pest species, such as oblique banded leafroller (OBLR), Choristoneura rosaceana (Harris), and peach twig borer (PTB), Anarsia lineatella (Zeller). Interestingly, in different trials the OFM Combo Dual combined with UV‐A LED light caught significantly more OFM and/or CM females compared to the OFM Combo Dual lure without light, opening the perspective for a female‐oriented monitoring and for a “female removal” management approach of these pests. The development of inexpensive, dual‐modality traps adding a light stimulus to a pheromone/kairomone lure may reduce monitoring costs in orchards with multiple moth pests, improving the trapping efficiency.
Metabolomic analysis revealed the inflammatory and oxidative stress regulation in response to Vibrio infection in Plectropomus leopardus
Authors: Wang Jie , Zhang Junwei , Shi Meng , Ma Xinran , Chen Songlin , Zhou Qian , Zhu Chunhua
Published: August 2024

Frequent outbreaks of infectious diseases in aquaculture have led to significant economic losses. The leopard coral grouper (Plectropomus leopardus) often suffers from vibriosis. Improving host immunity presents a superior strategy for disease control, with minimal side effects compared to the use of antibiotics, highlighting the necessity of exploring the mechanisms underlying the fish's response to pathogen infections. Here, we conducted a comparative metabolomic analysis on the livers of the P. leopardus infected with Vibrio harveyi. A total of 1124 differential metabolites (DMs) were identified, with 190, 218, 359, and 353 DMs being identified at 6, 12, 24, and 48 h post‐infection (hpi), respectively. Then, based on the time series analysis, we found that the lipid metabolism pathways were modulated in response to the Vibrio infection, with an increase in the quantity of eicosanoids and gycerophospholipids (GPLs), as well as a decrease in the quantity of bile acids (BAs), vitamin D, and sex hormones. Furthermore, 13 enriched pathways involving 31 DMs were identified through KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses. We identified histamine, 15(S)‐HpETE, and anandamide in the transient receptor potential (TRP) channels pathway, as well as (7S,8S)‐DiHODE, 5S,8R‐DiHODE, and 13(S)‐HpODE in the linoleic acid (LA) metabolism pathway. The DM levels increased, which may be attributed to inflammation. The DMs in the thyroid hormone synthesis pathway were identified, and the contents of nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH) decreased, which may be crucial in antioxidants. Our findings highlighted the dynamic adjustments in lipid metabolism and the response to inflammation and oxidative stress during the infection of V. harveyi in P. leopardus. This study not only deepens our understanding of the metabolic underpinnings of fish immune responses but also lays the groundwork for research into functional metabolomics and mechanisms of disease resistance.
HSP110 is a modulator of amyloid beta (Aβ) aggregation and proteotoxicity
Authors: Montresor Sabrina , Pigazzini Maria Lucia , Baskaran Sudarson , Sleiman Mira , Adhikari Govinda , Basilicata Lukas , Secker Luca , Jacob Natascha , Ehlert Yara , Kelkar Anushree , Kalsi Gurleen Kaur , Kulkarni Niraj , Spellerberg Paul , Kirstein Janine
Published: August 2024

Chaperones safeguard protein homeostasis by promoting folding and preventing aggregation. HSP110 is a cytosolic chaperone that functions as a nucleotide exchange factor for the HSP70 cycle. Together with HSP70 and a J‐domain protein (JDP), HSP110 maintains protein folding and resolubilizes aggregates. Interestingly, HSP110 is vital for the HSP70/110/JDP‐mediated disaggregation of amyloidogenic proteins implicated in neurodegenerative diseases (i.e., α‐synuclein, HTT, and tau). However, despite its abundance, HSP110 remains still an enigmatic chaperone, and its functional spectrum is not very well understood. Of note, the disaggregation activity of neurodegenerative disease‐associated amyloid fibrils showed both beneficial and detrimental outcomes in vivo. To gain a more comprehensive understanding of the chaperone HSP110 in vivo, we analyzed its role in neuronal proteostasis and neurodegeneration in C. elegans. Specifically, we investigated the role of HSP110 in the regulation of amyloid beta peptide (Aβ) aggregation using an established Aβ‐C. elegans model that mimics Alzheimer's disease pathology. We generated a novel C. elegans model that over‐expresses hsp‐110 pan‐neuronally, and we also depleted hsp‐110 by RNAi‐mediated knockdown. We assessed Aβ aggregation in vivo and in situ by fluorescence lifetime imaging. We found that hsp‐110 over‐expression exacerbated Aβ aggregation and appeared to reduce the conformational variability of the Aβ aggregates, whereas hsp‐110 depletion reduced aggregation more significantly in the IL2 neurons, which marked the onset of Aβ aggregation. HSP‐110 also plays a central role in growth and fertility as its over‐expression compromises nematode physiology. In addition, we found that HSP‐110 modulation affects the autophagy pathway. While hsp‐110 over‐expression impairs the autophagic flux, a depletion enhances it. Thus, HSP‐110 regulates multiple nodes of the proteostasis network to control amyloid protein aggregation, disaggregation, and autophagic clearance.

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An autopsy case of progressive supranuclear palsy with severe corticospinal tract degeneration
Authors: Kuru Satoshi , Sakai Motoko , Moriyoshi Hideyuki , Miyahara Hiroaki , Iwasaki Yasushi
Published: August 2024

We report an autopsy case of a 70‐year‐old man who was clinically diagnosed with atypical progressive supranuclear palsy (PSP). He initially presented with gait ataxia and then showed vertical gaze palsy, rigidity, akinesia, dysphagia, and mild cognitive impairment, followed by prominent upper motor signs later in the course of the disease. Cranial magnetic resonance imaging revealed tegmental atrophy of the midbrain. Autopsy revealed severe neuronal loss and gliosis in the motor cortex and corticospinal degeneration and mild to moderate neuronal loss and gliosis in the basal ganglia, substantia nigra, midbrain, and pons. Tufted astrocytes were primarily found in the motor cortex and basal ganglia. Globose‐type neurofibrillary tangles were observed in the locus coeruleus and nucleus olivaris inferior. In the cerebellar cortex, mild Purkinje cell loss and scattered axonal torpedoes were observed with tau‐positive Purkinje cells. The dentate nucleus displayed severe neuronal loss and gliosis. The present case showed characteristics of both PSP with prominent cerebellar ataxia (PSP‐C) and PSP‐primary lateral sclerosis (PSP‐PLS).
Investigating the impact of OCT imaging of the crystalline lens on the accuracy and precision of cataract assessment
Authors: Burke Niamh , Mulholland Pádraig J. , Keane Pearse A. , Little Julie‐Anne
Published: August 2024

Purpose

To determine if supplementing standard clinical assessments with Optical Coherence Tomography (OCT) imaging of the crystalline lens improves the accuracy and precision of lens opacity assessment and associated clinical management decisions by optometrists.

Methods

Fifty optometrists registered in the UK or Éire undertook a clinical vignette study where participants graded lens opacities and made associated clinical management decisions based on the image(s)/information displayed. Three forms of vignettes were presented: (1) Slit‐lamp (SL) images of the lens, (2) SL and OCT images and (3) SL, OCT and visual function measures. Vignettes were constructed using anonymised data from 50 patients with varying cataract severity, each vignette being presented twice in a randomised order (total vignette presentations = 300). The accuracy of opacity and management decisions were evaluated using descriptive statistics and non‐parametric Bland–Altman analysis where assessments from experienced clinicians were the reference. The precision of assessments was examined for each vignette form using non‐parametric Bland–Altman analysis.

Results

All (n = 50) participants completed the study, with 36 working in primary eyecare (primary eyecare) settings and 14 in hospital eyecare services (HES). Agreement was highest where vignettes contained all clinical data (i.e., SL, OCT and visual function data—grading: 51.0%, management: 50.5%), and systematically reduced with decreasing vignette content (p < 0.001). A larger number of vignettes containing imaging and visual function measures exhibited below reference (i.e., less conservative) grading compared with vignettes containing imaging data alone (all p < 0.05). HES‐based optometrists were more likely to grade lens opacities lower than clinicians working in primary eyecare (p < 0.001). Good measurement precision was evident for all vignettes, with a mean bias close to zero and limits of agreement below one grading step for all conditions.

Conclusions

The addition of anterior segment OCT to SL images improved the accuracy of lens opacity grading. Structural assessment alone yielded more conservative decision making, which reversed once visual functional data was available.
SUBSTANDARD STARCH GRAIN7 regulates starch grain size and endosperm development in rice
Authors: Yan Haigang , Ren Yulong , Zhang Binglei , Jin Jie , Du Feilong , Shan Zhuangzhuang , Fu Yushuang , Zhu Yun , Wang Xin , Zhu Changyuan , Cai Yue , Zhang Jie , Wang Fan , Zhang Xiao , Wang Rongqi , Wang Yongxiang , Xu Hancong , Jiang Ling , Liu Xi , Zhu Shanshan , Lin Qibing , Lei Cailin , Cheng Zhijun , Wang Yihua , Zhang Wenwei , Wan Jianmin
Published: August 2024

Starch is synthesized as insoluble, semicrystalline particles within plant chloroplast and amyloplast, which are referred to as starch grains (SGs). The size and morphology of SGs in the cereal endosperm are diverse and species–specific, representing a key determinant of the suitability of starch for industrial applications. However, the molecular mechanisms modulating SG size in cereal endosperm remain elusive. Here, we functionally characterized the rice (Oryza sativa) mutant substandard starch grain7 (ssg7), which exhibits enlarged SGs and defective endosperm development. SSG7 encodes a plant–specific DUF1001 domain‐containing protein homologous to Arabidopsis (Arabidopsis thaliana) CRUMPLED LEAF (AtCRL). SSG7 localizes to the amyloplast membrane in developing endosperm. Several lines of evidence suggest that SSG7 functions together with SSG4 and SSG6, known as two regulators essential for SG development, to control SG size, by interacting with translocon‐associated components, which unveils a molecular link between SG development and protein import. Genetically, SSG7 acts synergistically with SSG4 and appears to be functional redundancy with SSG6 in modulating SG size and endosperm development. Collectively, our findings uncover a multimeric functional protein complex involved in SG development in rice. SSG7 represents a promising target gene for the biotechnological modification of SG size, particularly for breeding programs aimed at improving starch quality.
MdWRKY31‐MdNAC7 regulatory network: orchestrating fruit softening by modulating cell wall‐modifying enzyme MdXTH2 in response to ethylene signalling
Authors: Wang Jia‐Hui , Sun Quan , Ma Chang‐Ning , Wei Meng‐Meng , Wang Chu‐Kun , Zhao Yu‐Wen , Wang Wen‐Yan , Hu Da‐Gang
Published: August 2024

Softening in fruit adversely impacts their edible quality and commercial value, leading to substantial economic losses during fruit ripening, long‐term storage, long‐distance transportation, and marketing. As the apple fruit demonstrates climacteric respiration, its firmness decreases with increasing ethylene release rate during fruit ripening and postharvest storage. However, the molecular mechanisms underlying ethylene‐mediated regulation of fruit softening in apple remain poorly understood. In this study, we identified a WRKY transcription factor (TF) MdWRKY31, which is repressed by ethylene treatment. Using transgenic approaches, we found that overexpression of MdWRKY31 delays softening by negatively regulating xyloglucan endotransglucosylase/hydrolases 2 (MdXTH2) expression. Yeast one‐hybrid (Y1H), electrophoretic mobility shift (EMSA), and dual‐luciferase assays further suggested that MdWRKY31 directly binds to the MdXTH2 promoter via a W‐box element and represses its transcription. Transient overexpression of ethylene‐induced MdNAC7, a NAC TF, in apple fruit promoted softening by decreasing cellulose content and increasing water‐soluble pectin content in fruit. MdNAC7 interacted with MdWRKY31 to form a protein complex, and their interaction decreased the transcriptional repression of MdWRKY31 on MdXTH2. Furthermore, MdNAC7 does not directly regulate MdXTH2 expression, but the protein complex formed with MdWRKY31 hinders MdWRKY31 from binding to the promoter of MdXTH2. Our findings underscore the significance of the regulatory complex NAC7–WRKY31 in ethylene‐responsive signalling, connecting the ethylene signal to XTH2 expression to promote fruit softening. This sheds light on the intricate mechanisms governing apple fruit firmness and opens avenues for enhancing fruit quality and reducing economic losses associated with softening.
X and Y Differences in Melanoma Survival Between the Sexes
Authors: Hersey Peter , Tseng Hsin‐Yi , Alavi Sara , Tiffen Jessamy
Published: August 2024

Marked differences in survival from melanoma are noted between men and women that cannot be accounted for by behavioral differences. We and others have provided evidence that this difference may be due to increased expression of immune‐related genes from the second X chromosome because of failure of X inactivation. In the present review, we have examined evidence for the contrary view that survival differences are due to weaker immune responses in males. One reason for this may be the loss of Y chromosomes (LOY), particularly in older males. The genes involved may have direct roles in immune responses or be noncoding RNAs that regulate both sex and autosomal genes involved in immune responses or tumor growth. Loss of the KDM6C and KDM5D demethylases appeared to common genes involved. The second factor appears to be the activation of androgen receptors (AR) on melanoma cells that increase their invasiveness and growth. Induction of T‐cell exhaustion by AR that limits immune responses against melanoma appeared a common finding. The development of treatments to overcome effects related to gene loss on Y poses challenges, but several avenues related to AR signaling appear worthy of further study in the treatment of metastatic disease.
Wittgenstein on mathematical facts
Authors: Berg Ásgeir
Published: August 2024

The status of mathematical facts has long been taken to be unclear in Wittgenstein's philosophy of mathematics, and often, it seems that he wants to eliminate mathematical facts in favour of facts about our beliefs or behaviour. In this paper, I argue that by reading Wittgenstein as a radical conventionalist, we can give a reading of the relevant passages according to which Wittgenstein doesn't deny that there are mathematical facts, but rather denies that one needs a metaphysical account of what mathematical facts are and how they relate to the world that goes beyond the minimal claims of radical conventionalism—that empirical facts about how we would find natural to project our training into new cases and the constitution of concepts by our agreement are enough. At the end of the paper, I discuss the implications of this reading on how to understand a rule's determination of its own application.
Providing red blood cells to facilitate organ transplant via normothermic perfusion techniques: A single‐center experience
Authors: Allen Elizabeth S. , Stephens Laura D. , Weber Nesinee , Brubaker Aleah L. , Hudson Ken , Pretorius Victor , Schnickel Gabriel , Kopko Patricia M.
Published: August 2024

Background

Normothermic regional perfusion (NRP) and normothermic machine perfusion (NMP) are organ procurement and transport techniques that can improve organ quality, facilitate longer transport, and reduce postoperative complications, increasing organ availability and improving outcomes. NRP and NMP often require allogeneic red blood cells (RBCs). Our academic transfusion service began providing RBCs to support NRP and NMP for adult heart transplant (HT), orthotopic liver transplant (OLT), and multiorgan transplant (MOT) in August 2020.

Methods

This single‐center, retrospective study describes the implementation process and analyzes the characteristics of RBC support during the first 3 years of the perfusion programs. Timing and quantity of units issued and used, organ recipient demographics, and transplant outcomes were obtained from transfusion service and electronic medical records.

Results

From 2020 to 2023, the transfusion service received 233 requests to support NRP and NMP perfusion cases. Of these, 105 cases resulted in RBC use, and units were returned or discarded in 112 cases. A total of 131 patients received perfusion‐facilitated transplants (92 HT, 27 OLT, and 12 MOT). The majority of perfusion‐facilitated HTs utilized NRP (81/92, 88%), whereas most perfusion‐facilitated OLTs utilized NMP (21/27, 78%). Across all 233 requests, a total of 381 RBC units were used to facilitate 131 transplants, averaging 2.91 units/transplant.

Discussion

Provision of RBCs for NRP and NMP techniques represents a novel method for transfusion services to support and facilitate life‐saving organ transplants with only modest product use, about three RBC units per organ transplant in this single‐center study.
Intraosseous contrast administration for coelomic computed tomography angiography in green iguanas (Iguana iguana): Preliminary findings show promise as an alternative to the intravenous route
Authors: Erickson Maëva C. M. , Gendron Karine P. , Aguilar Laura A. B. , Wyneken Jeanette , Walth Gregory B. , Gottdenker Nicole L. , Divers Stephen J.
Published: August 2024

Computed tomography is commonly used to evaluate the reptile coelom. One challenge in the acquisition of contrast‐enhanced CT studies in reptiles is the difficulty in placing intravenous catheters due to the poor conspicuity of peripheral vessels. To overcome these limitations, intraosseous catheterization of the long bones (humerus, femur, and tibia) can be used. The purpose of this prospective study was to assess the feasibility and diagnostic value of contrast‐enhanced CT of the coelom using a femoral intraosseous route for contrast administration. Twelve healthy juvenile green iguanas were enrolled. In 9 of 12 iguanas, vascular phases were obtained, providing strong, homogeneous enhancement of the arterial and venous tree concurrently. In these nine cases, Phase #1, acquired 60 s after beginning the injection of contrast medium, provided maximal contrast between the hepatic parenchyma and hepatic vasculature. In the remaining three cases, injection failure resulted from intracortical placement of the catheter tip. Histological examination of the liver, kidneys, and femur was performed to determine the pathomorphological correlates of the CT findings; in a third of patients, some degree of contrast‐induced renal toxicity was documented, which in mammalians shows potential for reversibility. Four iguanas had iatrogenic structural damage to the femoral growth plates attributed to intraosseous catheter placement. A femoral intraosseous route can be used in green iguanas for iodinated contrast medium administration for CT angiography. For the greatest contrast between coelomic organs and vascular structures, at least one postcontrast acquisition 60 s after initiation of contrast administration is recommended when using this technique.
The Role of AI in Enhancing Marketing Communication: Implications for Policy and Development in Indonesian Higher Education
Authors: Isnaini Santi , Muslimin Afif Ikhwanul
Published: August 2024

This research delves into the transformative impact of Artificial Intelligence (AI) on marketing communication within the Indonesian higher education sector. By adopting advanced AI technologies like machine learning algorithms, universities aim to enhance customer engagement, understand student behavior, and personalize marketing strategies. The study combines quantitative data, showcasing the extent of AI adoption and its outcomes, with qualitative insights to highlight the effectiveness of AI in improving key marketing metrics. Post-AI integration, there were significant increases in student inquiries, application rates, and enrollment numbers, underscoring the tangible benefits of AI-driven marketing strategies. The findings emphasize the strategic shift towards data-driven decision-making and personalized engagement, positioning Indonesian universities at the forefront of innovative marketing practices. This research contributes valuable insights for academia, industry practitioners, and policymakers looking to leverage AI for strategic marketing initiatives in higher education.
On finitely generated Engel branch groups
Authors: Petschick J. Moritz
Published: August 2024

We construct finitely generated Engel branch groups, answering a question of Fernández‐Alcober, Noce and Tracey on the existence of such objects. In particular, the groups constructed are not nilpotent, yielding the second known class of examples of finitely generated non‐nilpotent Engel groups following a construction by Golod from 1969. To do so, we exhibit groups acting on rooted trees with growing valency on which word lengths of elements are contracting very quickly under section maps. Our methods apply in principle to a wider class of iterated identities, of which the Engel words are a special case.
The revised JBI critical appraisal tool for the assessment of risk of bias for cohort studies
Authors: Barker Timothy H. , Hasanoff Sabira , Aromataris Edoardo , Stone Jennifer , Leonardi-Bee Jo , Sears Kim , Habibi Nahal , Klugar Miloslav , Tufanaru Catalin , Moola Sandeep , Liu Xian-Liang , Munn Zachary
Published: August 2024

Cohort studies are a robust analytical observational study design that explore the difference between two different cohorts on an outcome, differentiated by their exposure status. Despite being observational in nature, they are often included in systematic reviews of effectiveness, particularly when randomized controlled trials are limited or not feasible. Like all studies included in a systematic review, cohort studies must undergo a critical appraisal process to assess the extent to which a study has considered potential bias in its design, conduct, or analysis. Critical appraisal tools facilitate this evaluation. This paper introduces the revised critical appraisal tool for cohort studies, completed by the JBI Effectiveness Methodology Group (EMG), who are currently revising the suite of JBI critical appraisal tools for quantitative study designs. The revised tool responds to updates in methodological guidance from the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) Working Group and reporting guidance from PRISMA 2020, providing a robust framework for evaluating risk of bias in a cohort study. Transparent and rigorous assessment using this tool will assist reviewers in understanding the validity and relevance of the results and conclusions drawn from a systematic review that includes cohort studies. This may contribute to better evidence-based decision-making in health care. This paper discusses the key changes made to the tool, justifications for these changes, and provides practical guidance on how this tool should be interpreted and applied by systematic reviewers.
Subcutaneous and paraspinal tuberculous abscesses in a patient with Crohn’s disease
Authors: Karim Zohair , Abid Shahab
Published: August 2024

This case involves a man with longstanding Crohn’s disease on azathioprine therapy who developed a rare manifestation of tuberculosis, presenting as a subcutaneous tuberculous abscess and tuberculous spondylitis. The patient’s immunocompromised state due to azathioprine raised the risk for opportunistic infections. The unique aspects include the absence of disseminated tuberculosis and the development of tuberculous paraspinal and subcutaneous abscesses in a patient with Crohn’s disease. The case underscores the importance of vigilance for rare infections in immunosuppressed individuals and highlights the need for tuberculosis screening before initiating immunosuppressive therapies. The patient was successfully treated with antituberculous medication, emphasising the importance of a tailored approach in managing such cases.
Development and validation of optical coherence tomography (OCT) and OCT angiography prediction model for short-term vitreous haemorrhage secondary to polypoidal choroidal vasculopathy
Authors: Cheng Shiyu , Zhao Xinyu , Zhao Qing , Meng Lihui , Chen Youxin
Published: August 2024

Aims

To construct and validate an optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) image model for predicting the occurrence of short-term vitreous haemorrhage (VH) in polypoidal choroidal vasculopathy (PCV) patients.

Methods

We retrospectively collected clinical and imaging information from patients diagnosed with PCV at Peking Union Medical College Hospital, Beijing, China, between January 2015 and October 2022. Six different screening strategies, including univariate analysis, multivariate analysis, least absolute shrinkage and selection operator, stepwise logistic regression, random forest and clinical-data-only approach, were used to select variables and build models. The nomogram was constructed based on the model with the best area under the curve (AUC) and was evaluated using receiver operating characteristic curves, calibration curves, decision curve analysis and clinical impact curves.

Results

A total of 147 PCV patients were included and randomly divided into a training set (103 patients) and a validation set (44 patients), with an average follow-up time of 17.56±14.99 months. The optimal model that achieved higher AUC in both training and validation sets incorporated seven significant variables identified through univariate analysis: male [OR=2.76, p=0.022], central macular thickness [OR=1.003, p=0.002], the presence of haemorrhagic pigment epithelial detachment (HPED) [OR=6.99, p<0.001], the height of HPED [OR=1.002, p<0.001], the area of HPED [OR=1.16, p<0.001], the presence of multiple PEDs [OR=2.94, p=0.016] and the presence of subretinal haemorrhage [OR=3.11, p=0.011]. A predictive nomogram based on these variables yielded an AUC of 0.896 (95% CI 0.827 to 0.965) in the training set and 0.861 (95% CI 0.749 to 0.973) in the validation set, demonstrating good calibration and clinical usefulness.

Conclusion

The proposed OCT/OCTA-based image nomogram, as a novel and non-invasive tool, achieved satisfactory prediction of VH secondary to PCV.
Association betweenHelicobacter pyloriand its eradication and the development of cancer
Authors: Loosen Sven Heiko , Mertens Alexander , Klein Isabel , Leyh Catherine , Krieg Sarah , Kandler Jennis , Luedde Tom , Roderburg Christoph , Kostev Karel
Published: August 2024

Background

Helicobacter pylori(H. pylori) is a gram-negative gastrointestinal pathogen that colonises the human stomach and is considered a major risk factor for gastric cancer and mucosa-associated lymphoid tissue lymphoma. Furthermore,H. pyloriis a potential trigger of a wide spectrum of extragastric cancer entities, extraintestinal chronic inflammatory processes and autoimmune diseases. In the present study, we evaluated the association betweenH. pyloriinfection and its eradication with the development of subsequent gastrointestinal and non-gastrointestinal cancer.

Methods

We identified 25 317 individuals with and 25 317 matched individuals without a diagnosis ofH. pylorifrom the Disease Analyzer database (IQVIA). A subsequent cancer diagnosis was analysed using Kaplan-Meier and conditional Cox-regression analysis as a function ofH. pyloriand its eradication.

Results

After 10 years of follow-up, 12.8% of theH. pyloricohort and 11.8% of the non-H. pyloricohort were diagnosed with cancer (p=0.002). Results were confirmed in regression analysis (HR: 1.11; 95% CI 1.04 to 1.18). Moreover, a non-eradicatedH. pyloristatus (HR: 1.18; 95% CI 1.07 to 1.30) but not an eradicatedH. pyloristatus (HR: 1.06; 95% CI 0.97 to 1.15) was associated with a subsequent diagnosis of cancer. In subgroup analyses,H. pylorieradication was negatively associated with bronchus and lung cancer (HR: 0.60; 95% CI 0.44 to 0.83).

Conclusion

Our data from a large outpatient cohort in Germany reveal a distinct association betweenH. pyloriinfection and the subsequent development of cancer. These data might help to identify patients at risk and support eradication strategies in the future.
Epidemiological trends of febrile infants presenting to the Paediatric Emergency department, in a tertiary care hospital, Karachi, Pakistan: a retrospective review
Authors: Bushra Quratulain , Fatima Sara , Hameed Ammara , Mukhtar Sama
Published: August 2024

Background

Understanding the epidemiological patterns of febrile infants can offer valuable insights for optimising management strategies and developing quality improvement initiatives, aiming to improve healthcare delivery in high-volume, low-resource emergency departments (EDs).

Objectives

To characterise the epidemiology of febrile infants presenting to the paediatric ED of a tertiary care hospital.

Methods

A retrospective chart review of medical records was performed for febrile infants ≤1 year old, at paediatric ED, Indus Hospital and Health Network (IHHN), Karachi, Pakistan (1 January 2020–31 December 2020).

Results

There were a total of 2311 patients in the study, with a male-to-female ratio of 1.4:1. The mean age of presentation was 4.9±2.7 months. Cough (n=1002, 43.2%) was the most frequent presenting symptom. The most common provisional ED diagnosis in ≤1 month of age was sepsis (n=98, 51%), bronchopneumonia (n=138, 28.6%) in 1.1–3 and 3.1–6 months (n=176, 36.45%); and upper respiratory tract illness (n=206, 47.4%) in 6.1–12 months of age. Age was significantly associated with provisional ED diagnosis and outcomes (p<0.001). Of 175 ED admissions (n=47, 26.8%), patients were discharged with a hospital diagnosis of bronchopneumonia and (n=27, 15.4) of sepsis. The infant mortality rate was 3/1000 live births.

Conclusions

This study is the first of its kind to explore the epidemiology of febrile infants in Pakistan, highlighting the burden and severity of respiratory illnesses and sepsis. It underscores the challenges of resource-limited settings, failing to meet the need for admission of febrile infants presenting to ED, IHHN. Moreover, it has highlighted the necessity to optimise the existing triage systems to effectively allocate resources and manage high patient volumes in low-resource EDs.
Systematic review protocol to determine the most effective pharmacological and non-pharmacological interventions for the management of acute methamphetamine toxicity
Authors: Ghosh Sumantra Monty , Kung Janice Y , Crockford David , Harpur Lisa , Tanguay Robert , Dyer Dianne , Lang Eddy , Ayas Tim , Feng Gregory , VandenBerg Stephanie D
Published: August 2024

Introduction

This study describes the protocol for a systematic review. The systematic review will address experiences of managing methamphetamine intoxication, specifically violence and agitation related to intoxication, in the emergency department (ED).

Methods and analysis

This study uses the Grading of Recommendations Assessment, Development and Evaluation system to guide the methods in this section. The primary objective of the review is to identify experimental studies assessing the effectiveness of both pharmacological and non-pharmacological strategies to manage acute methamphetamine intoxication in patients presenting violently in the ED. Our secondary objectives will be to assess the impact of specific strategies on the time it takes to achieve de-escalation and/or sedation, the length of stay in the ED, frequency of admission, mortality and provider satisfaction with the intervention.

Ethics and dissemination

Ethics approval has been obtained from the Conjoint Health Research Ethics Board REB21-1387. Results will be published in a peer-reviewed journal and presented at healthcare conferences in Canada.

Trial registration number

The protocol is registered through the International Prospective Register of Systematic Reviews (identification number: CRD42020157938) and will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extensions for systematic review protocols.
Mapping cognitive biases in multidisciplinary team (MDT) decision-making for cancer care in Scotland: a cognitive ethnography study protocol
Authors: Dharanikota Harini , Wigmore Stephen J , Skipworth Richard , Yule Steven
Published: August 2024

Introduction

The efficiency of multidisciplinary teams (MDTs) in cancer care hinges on facilitating clinicians’ cognitive processes as they navigate complex and uncertain judgements during treatment planning. When systems and workflows are not designed to adequately support human judgement and decision-making, even experts are prone to fallible reasoning due to cognitive biases. Incomplete integration of information or biased interpretations of patient data can lead to clinical errors and delays in the implementation of treatment recommendations. Though their impact is intuitively recognised, there is currently a paucity of empirical work on cognitive biases in MDT decision-making. Our study aims to explicate the impact of such biases on treatment planning and establish a foundation for targeted investigations and interventions to mitigate their negative effects.

Methods and analysis

This is a qualitative, observational study. We employ cognitive ethnography, informed by the Distributed Cognition for Teamwork framework to assess and evaluate MDT decision-making processes. The study involves in-person and virtual field observations of hepatopancreaticobiliary and upper gastrointestinal MDTs and interviews with their members over several months. The data generated will be analysed in a hybrid inductive/deductive fashion to develop a comprehensive map of potential cognitive biases in MDT decision processes identifying antecedents and risk factors of suboptimal treatment planning processes. Further, we will identify components of the MDT environment that can be redesigned to support decision-making via development of an MDT workspace evaluation tool.

Ethics and dissemination

This project has received management and ethical approvals from NHS Lothian Research and Development (2023/0245) and the University of Edinburgh Medical School ethical review committee (23-EMREC-049). Findings will be shared with participating MDTs and disseminated via a PhD thesis, international conference presentations and relevant scientific journals.
Impact of altitude on the development of low bone mineral density and osteoporosis in individuals aged 50 years and older: protocol for a multicentre prospective cohort study
Authors: Zhang Fengying , Chen Yanli , Wang Suyuan , Shi Zhiyou , Zhong Yang , Zhu Suying , Wangmu Ciren , Wu Yunhong
Published: August 2024

Introduction

Osteoporotic fractures are a leading cause of disability and contribute significantly to medical care costs worldwide. Variations in bone mineral density and the risk of osteoporosis are notably influenced by altitude. This study aims to longitudinally examine individuals with osteoporosis and low bone mass at three different altitudes (low, high and very high) to understand the effects of high-altitude environments on bone density.

Methods and analysis

This multicentre, prospective cohort study will involve 893 participants divided into three groups based on altitude: low (500–1500 m), high (2500–4500 m) and very high (4500–5500 m). Participants will undergo comprehensive diagnostic assessments, including demographic data collection, structured questionnaires, medical examinations and clinical laboratory tests. Follow-up visits will occur annually for a minimum of 5 years. The primary outcome will be changes in bone mineral density values. Secondary outcomes will include the incidence of osteoporosis and osteoporotic fractures. Cox proportional hazard models will be used to calculate the risk associated with osteoporotic events and related fractures.

Ethics and dissemination

The study has been approved by the Institutional Review Board of the Hospital of Chengdu Office of People’s Government of Tibetan Autonomous Region (No: 2024-70). The acquired insights will be disseminated via academic forums, scholarly articles and stakeholder engagement sessions.

Trial registrationnumber

ChiCTR2300078872.
Economic impact of COVID-19 on patients with type 2 diabetes in Kenya and Tanzania: a costing analysis
Authors: Karugu Caroline H , Binyaruka Peter , Ilboudo Patrick G , Sanya Richard E , Mohamed Shukri F , Kisia Lyagamula , Kibe Peter , Mashiashi Irene , Bunn Christopher , Mair F , Agyemang Charles , Mtenga Sally M , Asiki Gershim , Gray Cindy M , Grieve Eleanor , Deidda Manuela
Published: August 2024

Introduction

COVID-19 affected healthcare access, utilisation and affordability, especially for patients suffering from chronic diseases, including type 2 diabetes (T2D). This study measured the occurrence and magnitude of changes in healthcare and broader societal costs among patients with T2D before and during COVID-19 in Kenya and Tanzania to understand whether and how COVID-19 affected T2D management in countries implementing different policies during the pandemic.

Methods

A cross-sectional study was conducted in Kenya and Tanzania in March–April 2022 among 500 patients with T2D in each country. We interviewed patients on direct healthcare costs (eg, inpatient and outpatient costs), societal costs (eg, productivity loss) and patients’ characteristics before and during the COVID-19 pandemic. We estimated changes over time using the Generalised Linear Model in Kenya and a two-part model in Tanzania, adjusting for patient-level covariates.

Results

The overall costs of management of T2D in most categories increased in both countries during COVID-19, but some of the increase was not significant. Transport and testing costs increased significantly in Tanzania (I$0.33, p<0.01 and I$0.85, p<0.01) but not in Kenya (I$1.69, p=0.659 and I$0.10, p=0.603). Outpatient costs increased significantly in Tanzania (I$8.84, p<0.01) but there was no significant change in Kenya (I$8.09, p=0.432). T2D medication costs did not change in Tanzania (I$0.19, p=0.197), but decreased significantly in Kenya (I$18.48, p<0.01). Productivity losses increased significantly in both countries.

Conclusion

The COVID-19 pandemic is associated with increased direct costs but with a significant increase in many cost categories (transport, testing and outpatient) in Tanzania than in Kenya. A significant increase in productivity loss was observed in both countries. The minimal cost increases in Kenya may be due to the inaccessibility of services associated with lockdown measures and higher insurance coverage compared with Tanzania. Pandemic preparedness initiatives and interventions are needed to safeguard the welfare of patients with chronic conditions during pandemics.
Does arts and cultural group participation influence subsequent well-being? A longitudinal cross-country comparison of older adults in Japan and England
Authors: Bone Jessica K , Noguchi Taiji , Mak Hei Wan , Fancourt Daisy , Kondo Katsunori , Saito Tami
Published: August 2024

Introduction

Arts engagement is a positive health behaviour that could support the mental and social well-being of ageing populations globally. However, research is predominantly from Western countries, leaving it unclear whether arts engagement can support well-being in Japan, where arts are differently valued and engaged with. The social gradient in arts engagement and well-being may also have led to an overestimation of the impact of participation on well-being in Western countries. We therefore tested whether participation in community arts and cultural groups was associated with subjective well-being and social support after removing confounding by demographic, socioeconomic and health-related factors in Japan and England.

Methods

We harmonised longitudinal data from the Japan Gerontological Evaluation Study (JAGES) 2016 and 2019 waves and the English Longitudinal Study of Ageing (ELSA) 2014 and 2018 waves to enable cross-country comparisons. We included 9511 adults aged ≥65 years from JAGES and 3133 participants aged ≥65 years from ELSA. Using inverse probability-weighted regression adjustment, we estimated the effect of arts and cultural groups on subsequent life satisfaction, happiness and depressive symptoms (subjective well-being) as well as social support.

Results

In JAGES, arts and cultural group participation was associated with higher odds of life satisfaction and higher social support scores. In ELSA participants aged ≥65 years, group participation was only associated with higher depressive symptoms. But, in a sensitivity analysis with the full ELSA sample aged ≥50 years (n=5128), this association was no longer present. Instead, group participation was associated with higher social support scores.

Conclusion

Our findings indicate that arts and cultural group participation can enhance life satisfaction and social support in Japan, with small but more consistent benefits than in England. Facilitating participation in arts and cultural groups could help older adults to maintain a healthy social support network, which may further support their health as they age.