bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical utility of point‐of‐care glucose testing in the assessment of gestational diabetes: Prospective cohort study
Authors: Al‐Hasani Wiaam , Ranasinghe Ruvini , Rogers Helen , Spanier William , Spears Katie , Gayle Carol , Long Lisa , Dimitriadis Georgios K. , Hunt Katharine F. , Vincent Royce P.
Published: March 2024

Objective

To assess the clinical utility of point‐of‐care (POC) capillary blood glucose (CBG) testing in the assessment of gestational diabetes mellitus (GDM) during oral glucose tolerance test (OGTT).

Design

Prospective cohort study.

Setting

Antenatal clinics at King's College Hospital.

Population

Women screened for GDM between March and June 2020.

Methods

The CBG was measured using the POC StatStrip® test and the venous plasma glucose (VPG) was measured by Roche analyser (Cobas 8000 c702). GDM was diagnosed based on the 2015 National Institute for Health and Clinical Excellence (NICE) Clinical Guideline criteria. The two methods were compared statistically using Analyse‐It 5.40.2.

Main outcome measures

Diagnostic sensitivity, specificity, positive and negative predictive values (PPV and NPV) for the POC StatStrip® test, compared with VPG measured by reference laboratory method.

Results

A total of 230 women were included. The number and percentage of women with glucose concentrations above the GDM threshold using the POC StatStrip® test versus laboratory VPG measurement was 15 (6.5%) versus eight (3.4%) at fasting and 105 (45.6%) versus 72 (31.1%) at 2 h, respectively. The sensitivity and specificity values (and 95% CIs) for the POC StatStrip® test were 88% (52%–99%) and 97% (93%–98%) at fasting and 97% (91%–99%) and 79% (71%–84%) at 2 h, respectively. However, the specificity and the NPV for the POC StatStrip® test for concentrations of ≤5.0 mmol/L at fasting or <7.5 mmol/L at 2 h were 100%, and the sensitivity and the PPV for concentrations of >9.5 mmol/L at 2 h were 100%.

Conclusions

In our cohort the POC measurement of CBG cannot entirely replace the laboratory method for the OGTT; however, it can be used to rule out/rule in GDM for glucose concentrations of ≤5.0 mmol/L at fasting or <7.5/>9.5 mmol/L at 2 h.
PIEZO1 acts as a cancer suppressor by regulating the ROS/Wnt/β‐catenin axis
Authors: Bo Haimei , Wu Qi , Zhu Chaonan , Zheng Yang , Cheng Guang , Cui Lihua
Published: March 2024

Background

PIEZO1 works differently in different cancers and at different stages of development. The objective of the current study was to explore the function and underlying mechanism of PIEZO1 in lung adenocarcinoma (LUAD) cells.

Methods

Different LUAD cell lines were treated with PIEZO1 inhibitor (GsMTx4) and agonist (Yoda1), and the expression of PIEZO1 in LUAD cells was detected using real‐time quantitative PCR (RT‐qPCR) and western blotting. The effects of PIEZO1 on invasion, migration and epithelial‐mesenchymal transition (EMT) markers protein expression of LUAD cells were detected using the MTT assay, flow cytometry, transwell assay, wound‐healing assay, and western blotting. Reactive oxygen species (ROS) agonists (BAY 87–2243) and inhibitors (NAC) and Wnt/β‐catenin pathway inhibitors (iCRT3) were selected to treat A549 cells to investigate the mechanism of PIEZO1 on ROS production and Wnt/β‐catenin expression in A549 cells.

Results

In A549, NCI‐H1395, and NCI‐H1975 cells, GsMTx4 promoted cell proliferation, invasion, migration, upregulated EMT‐related marker protein expression, and inhibited cell apoptosis, while Yoda1 exerted effects opposite to those of GsMTx4. In A549 cells, GsMTx4 can reduce ROS production, it also inhibited ROS production, apoptosis, and downregulated proapoptotic markers induced by BAY 87–2243. Importantly, BAY 87–2243 blocked the effect of GSMTX4‐induced Wnt/β‐catenin overexpression. Similarly, Yoda1 can reduce the effect of NAC. In addition, iCRT3 can block the upregulation of EMT‐related marker proteins by GsMTx4, and increase apoptosis and decrease cell invasion and migration.

Conclusion

In summary, PIEZO1 acts as a cancer suppressor by regulating the ROS/Wnt/β‐catenin axis, providing a new perspective on the role of mechanosensitive channel proteins in cancer.
The emergency department trigger tool: Multicenter trigger query validation
Authors: Griffey Richard T. , Schneider Ryan M. , Kocher Keith E. , Kwok Edmund S. H. , Salmo Ellen , Malone Nora , Smith Carrie , Guarnacia Catie , Rick April , Clavet Tamara , Asaro Phil , Medlin Rich , Todorov Alexandre A.
Published: March 2024

Objectives

We previously described derivation and validation of the emergency department trigger tool (EDTT) for adverse event (AE) detection. As the first step in our multicenter study of the tool, we validated our computerized screen for triggers against manual review, establishing our use of this automated process for selecting records to review for AEs.

Methods

This is a retrospective observational study of visits to three urban, academic EDs over 18 months by patients ≥ 18 years old. We reviewed 912 records: 852 with at least one of 34 triggers found by the query and 60 records with none. Two first‐level reviewers per site each manually screened for triggers. After completion, computerized query results were revealed, and reviewers could revise their findings. Second‐level reviewers arbitrated discrepancies. We compare automated versus manual screening by positive and negative predictive values (PPVs, NPVs), present population trigger frequencies, proportions of records triggered, and how often manual ratings were changed to conform with the query.

Results

Trigger frequencies ranged from common (>25%) to rare (1/1000) were comparable at U.S. sites and slightly lower at the Canadian site. Proportions of triggered records ranged from 31% to 49.4%. Overall query PPV was 95.4%; NPV was 99.2%. PPVs for individual trigger queries exceeded 90% for 28–31 triggers/site and NPVs were >90% for all but three triggers at one site. Inter‐rater reliability was excellent, with disagreement on manual screening results less than 5% of the time. Overall, reviewers amended their findings 1.5% of the time when discordant with query findings, more often when the query was positive than when negative (47% vs. 23%).

Conclusions

The EDTT trigger query performed very well compared to manual review. With some expected variability, trigger frequencies were similar across sites and proportions of triggered records ranged 31%–49%. This demonstrates the feasibility and generalizability of implementing the EDTT query, providing a solid foundation for testing the triggers’ utility in detecting AEs.
Predicting alcohol relapse post‐detoxification: The role of cognitive impairments in alcohol use disorder patients
Authors: Teixeira Joana , Pinheiro Maria , Pereira Gabriela Álvares , Nogueira Paulo , Guerreiro Manuela , Castanho Miguel , do Couto Frederico Simões
Published: March 2024

Background

Studies on early abstinence suggest that cognitive function is significantly reduced in the first year of abstinence, which raises the question of whether it is relevant to early relapse in patients with substance use disorders. This study investigates the extent to which impairments in executive function and memory predict alcohol relapse in patients with alcohol use disorder (AUD). Understanding these relationships is crucial for improving therapeutic approaches to prevent relapse in patients with AUD.

Methods

We selected 116 adult patients (79 male and 37 female) diagnosed with AUD based on DSM‐5 criteria, all of whom were undergoing alcohol detoxification treatment. A comprehensive array of neuropsychological tests was administered to assess global cognition, memory, and executive functions. Patients' alcohol use was monitored monthly during a 6‐month follow‐up period. Logistic regression and Cox regression were used to explore the relationship between cognitive function and the likelihood of alcohol relapse.

Results

Impairments in global cognition, semantic and phonemic fluency, cognitive flexibility, and learning ability during detoxification were significant predictors of relapse in AUD patients, showing similar predictive values at both 3 and 6 months post‐treatment. An abnormal Montreal Cognitive Assessment (MoCA) score increased the risk of relapse by 123% (HR: 2.227), and impairments in both semantic and phonemic fluency each increased the risk by 142% (HR: 2.423). Additionally, abnormal performance on the MoCA, Trail Making Test Part B (TMT‐B), and California Verbal Learning Test (CVLT) was associated with a higher number of drinking days at 3 months (IRR: 3.764; IRR: 2.237; IRR: 2.738, respectively) and abnormal MoCA and TMT‐B scores at 6 months (IRR: 2.451; IRR: 1.859, respectively).

Conclusions

The MoCA test is a valuable tool for predicting relapse risk in AUD patients undergoing detoxification treatment, with similar predictive value for relapse at 3 or 6 months. Learning ability needs to be assessed and their impairments considered in the treatment of AUD patients. Future research should explore strategies for managing patients with impairments in memory and learning ability to enhance treatment effectiveness and prevent relapse.
Regional modulation of toll‐like receptor signaling pathway genes in acute epididymitis in mice
Authors: Andrade Alexandre D. , Almeida Priscila G. C. , Mariani Noemia A. P. , Santos Natalia C. M. , Camargo Isabela A. , Martini Poliana V. , Kushima Helio , Ai Dingding , Avellar Maria Christina W. , Meinhardt Andreas , Pleuger Christiane , Silva Erick J. R.
Published: March 2024

Background

Region‐specific immune environments in the epididymis influence the immune responses to uropathogenic Escherichia coli (UPEC) infection, a relevant cause of epididymitis in men. Toll‐like receptors (TLRs) are essential to orchestrate immune responses against bacterial infections. The epididymis displays region‐specific inflammatory responses to bacterial‐derived TLR agonists, such as lipopolysaccharide (LPS; TLR4 agonist) and lipoteichoic acid (LTA; TLR2/TLR6 agonist), suggesting that TLR‐associated signaling pathways could influence the magnitude of inflammatory responses in epididymitis.

Objectives

To investigate the expression and regulation of key genes associated with TLR4 and TLR2/TLR6 signaling pathways during epididymitis induced by UPEC, LPS, and LTA in mice.

Material and methods

Epididymitis was induced in mice using UPEC, ultrapure LPS, or LTA, injected into the interstitial space of the initial segment or the lumen of the vas deferens close to the cauda epididymidis. Samples were harvested after 1, 5, and 10 days for UPEC‐treated animals and 6 and 24 h for LPS‐/LTA‐treated animals. Ex vivo epididymitis was induced by incubating epididymal regions from naive mice with LPS or LTA. RT‐qPCR and Western blot assays were conducted.

Results

UPEC infection up‐regulated Tlr2, Tlr4, and Tlr6 transcripts and their associated signaling molecules Cd14, Ticam1, and Traf6 in the cauda epididymidis but not in the initial segment. In these epididymal regions, LPS and LTA differentially modulated Tlr2, Tlr4, Tlr6, Cd14, Myd88, Ticam1, Traf3, and Traf6 expression levels. NFKB and AP1 activation was required for LPS‐ and LTA‐induced up‐regulation of TLR‐associated signaling transcripts in the cauda epididymidis and initial segment, respectively.

Conclusion

The dynamic modulation of TLR4 and TLR2/TLR6 signaling pathways gene expression during epididymitis indicates bacterial‐derived antigens elicit an increased tissue sensitivity to combat microbial infection in a spatial manner in the epididymis. Differential activation of TLR‐associated signaling pathways may contribute to fine‐tuning inflammatory responses along the epididymis.
Efficacy and safety of filgotinib for ulcerative colitis: A real‐world multicenter retrospective study in Japan
Authors: Akiyama Shintaro , Yokoyama Kaoru , Yagi Soichi , Shinzaki Shinichiro , Tsuruta Kozo , Yoshioka Shinichiro , Sako Minako , Shimizu Hiromichi , Kobayashi Mariko , Sakurai Toshiyuki , Nomura Kei , Shibuya Tomoyoshi , Takahara Masahiro , Hiraoka Sakiko , Sugai Kyohei , Yanai Shunichi , Yoshida Atsushi , Koroku Miki , Omori Teppei , Saruta Masayuki , Matsumoto Takayuki , Okamoto Ryuichi , Tsuchiya Kiichiro , Fujii Toshimitsu
Published: March 2024

Background and Aims

While filgotinib, an oral Janus kinase (JAK) 1 preferential inhibitor, is approved for moderately to severely active ulcerative colitis (UC), real‐world studies assessing its short‐ and long‐term efficacy and safety are limited.

Methods

This is a multicenter, retrospective study of UC patients who started filgotinib between March 2022 and September 2023. The primary outcome was clinical remission, defined as a partial Mayo score ≤1 with a rectal bleeding score of 0, or Simple Clinical Colitis Activity Index (SCCAI) ≤2 with a blood‐in‐stool score of 0. Secondary outcomes included clinical response, corticosteroid‐free remission, and endoscopic improvement. Outcomes were assessed at 10, 26, and 58 weeks based on patients with available follow‐up. Adverse events were evaluated.

Results

We identified 238 UC patients and 54% had prior exposure to biologics/JAK inhibitors. The median baseline partial Mayo score and SCCAI were 5 (IQR 3–6) and 4 (IQR 2–7). Clinical remission rates based on per‐protocol analysis at 10, 26, and 58 weeks were 47% (70/149), 55.8% (48/86), and 64.6% (31/48), respectively. At a median follow‐up of 28 weeks (IQR 10–54) with a discontinuation rate of 39%, the rates of clinical remission, clinical response, corticosteroid‐free remission, and endoscopic improvement were 39.9% (81/203), 54.7% (111/203), and 36.5% (74/203), and 43.5% (10/23), respectively. These rates were comparable between biologic/JAK inhibitor‐naïve and ‐experienced patients. While three patients (1.3%) developed herpes zoster infection, no cases of thrombosis or death were reported.

Conclusions

Real‐world data demonstrate favourable clinical and safety outcomes of filgotinib for UC.
Safe suprapancreatic lymph node dissection for gastric cancer with ectopic common hepatic artery
Authors: Toyota Kazuhiro , Ishida Hayato , Mori Masayuki , Okamoto Nobuyuki , Kuraoka Norimasa , Yano Raita , Kobayashi Hironori , Hashimoto Yasushi , Sakashita Yoshihiro , Yokoyama Yujiro , Murakami Yoshiaki , Ishida Hiroshi , Takahashi Shinya , Miyamoto Katsunari
Published: March 2024

Suprapancreatic lymph node dissection for patients with gastric cancer in whom the common hepatic artery is located neither at the suprapancreatic margin nor in front of the portal vein is a more difficult procedure than when the common hepatic artery is in a more typical position. There is an increased risk of injury to the vessels that need to be preserved and inadequate lymph node dissection. Measures that have been reported for use in this situation are preoperative diagnosis with three‐dimensional computed tomography angiography, dissection using the portal vain as a guide, and safe exposure of the portal vein with dissection to preserve the nerves at the suprapancreatic margin and in front of the portal vein. We review the literature and report our experience with a patient whose common hepatic artery was not located in the suprapancreatic margin who safely underwent suprapancreatic lymph node dissection using these methods.
Evolution of snake skin: Role of cutaneous tactile corpuscles in Hierophis viridiflavus (Lacépède, 1789)
Authors: Alesci Alessio , Marino Sebastian , Di Fresco Dario , Miller Anthea , Saccardi Laura , Famulari Sergio , Albano Marco , Di Paola Davide , Spanò Nunziacarla , Lauriano Eugenia Rita
Published: March 2024

The skin of snakes acts as the first interface between these reptiles and the environment they live in. It plays an important role in the ecology of these organisms, and specialised structures, such as tactile corpuscles, are crucial in the sensing of a wide variety of stimuli. This study, by examining the presence, localisation and colocalisation of serotonin, substance P, PGP 9.5 and tubulin, wants to demonstrate the sensory role that these structures play in the ecology of the Green whip snake Hierophis viridiflavus (Lacépède, 1789). This study presents the first evaluation of nerve and immune molecules (TLR2) in the tactile corpuscles of H. viridiflavius ventral skin, indicating a potential defence role of these structures. These findings provide valuable information on the ecology of snakes, their defence systems, and their evolutionary morphostructural adaptations. Additionally, the identification of these corpuscles could provide valuable support for taxonomic recognition. Furthermore, this study expands the knowledge about stimuli sensing in snakes.
Health care professionals' knowledge and attitudes towards antibiotic prescribing for the treatment of urinary tract infections: A systematic review
Authors: Mwape Angela Kabulo , Schmidtke Kelly Ann , Brown Celia
Published: March 2024

Purpose

Previous models identify knowledge and attitudes that influence prescribing behaviour. The present study focuses on antibiotic prescribing for urinary tract infections (UTIs) to describe levels of health care professionals' knowledge and attitude factors in this area and how those levels are assessed.

Methods

A systematic search was conducted to identify studies assessing the identified knowledge or attitude factors influencing health care professionals' antibiotic prescribing for urinary tract infections up to September 2022. Study quality was assessed using the Newcastle–Ottawa scale. Data were extracted about the types of factors assessed, the levels indicated and how those levels were assessed. Data were synthesized using counts, and levels were categorized as ‘poor’, ‘moderate’, ‘high’ or ‘very high’.

Results

Seven studies were identified, six of which relied entirely on closed‐ended items. Levels of knowledge factors assessed were poor, for example, their ‘knowledge of condition’ and ‘knowledge of task environment’ were poor. Levels of the attitude factors assessed varied, for example, while health care professionals expressed moderate confidence in providing optimal patient care and appropriate attitude of fear towards the problem of antibiotic resistance, they expressed a poor attitude of complacency by giving into patient pressure to prescribe an antibiotic.

Conclusions

Present evidence suggests that clinicians have poor levels of knowledge and varying levels of attitudes about antibiotic prescribing for UTIs. However, few studies were identified, and assessments were largely limited to closed‐ended types of questions. Future studies that assess more factors and employ open‐ended question types could better inform future interventions to optimize antibiotic prescribing.
The Emotional Content of Children's Writing: A Data‐Driven Approach
Authors: Dong Yuzhen , Hsiao Yaling , Dawson Nicola , Banerji Nilanjana , Nation Kate
Published: March 2024

Emotion is closely associated with language, but we know very little about how children express emotion in their own writing. We used a large‐scale, cross‐sectional, and data‐driven approach to investigate emotional expression via writing in children of different ages, and whether it varies for boys and girls. We first used a lexicon‐based bag‐of‐words approach to identify emotional content in a large corpus of stories (N>100,000) written by 7‐ to 13‐year‐old children. Generalized Additive Models were then used to model changes in sentiment across age and gender. Two other machine learning approaches (BERT and TextBlob) validated and extended these analyses, converging on the finding that positive sentiments in children's writing decrease with age. These findings echo reports from previous studies showing a decrease in mood and an increased use of negative emotion words with age. We also found that stories by girls contained more positive sentiments than stories by boys. Our study shows the utility of large‐scale data‐driven approaches to reveal the content and nature of children's writing. Future experimental work should build on these observations to understand the likely complex relationships between written language and emotion, and how these change over development.
Recursive Numeral Systems Optimize the Trade‐off Between Lexicon Size and Average Morphosyntactic Complexity
Authors: Denić Milica , Szymanik Jakub
Published: March 2024

Human languages vary in terms of which meanings they lexicalize, but this variation is constrained. It has been argued that languages are under two competing pressures: the pressure to be simple (e.g., to have a small lexicon) and to allow for informative (i.e., precise) communication, and that which meanings get lexicalized may be explained by languages finding a good way to trade off between these two pressures. However, in certain semantic domains, languages can reach very high levels of informativeness even if they lexicalize very few meanings in that domain. This is due to productive morphosyntax and compositional semantics, which may allow for construction of meanings which are not lexicalized. Consider the semantic domain of natural numbers: many languages lexicalize few natural number meanings as monomorphemic expressions, but can precisely convey very many natural number meanings using morphosyntactically complex numerals. In such semantic domains, lexicon size is not in direct competition with informativeness. What explains which meanings are lexicalized in such semantic domains? We will propose that in such cases, languages need to solve a different kind of trade‐off problem: the trade‐off between the pressure to lexicalize as few meanings as possible (i.e, to minimize lexicon size) and the pressure to produce as morphosyntactically simple utterances as possible (i.e, to minimize average morphosyntactic complexity of utterances). To support this claim, we will present a case study of 128 natural languages' numeral systems, and show computationally that they achieve a near‐optimal trade‐off between lexicon size and average morphosyntactic complexity of numerals. This study in conjunction with previous work on communicative efficiency suggests that languages' lexicons are shaped by a trade‐off between not two but three pressures: be simple, be informative, and minimize average morphosyntactic complexity of utterances.
Evaluating the Relative Importance of Wordhood Cues Using Statistical Learning
Authors: Pankratz Elizabeth , Kirby Simon , Culbertson Jennifer
Published: March 2024

Identifying wordlike units in language is typically done by applying a battery of criteria, though how to weight these criteria with respect to one another is currently unknown. We address this question by investigating whether certain criteria are also used as cues for learning an artificial language—if they are, then perhaps they can be relied on more as trustworthy top‐down diagnostics. The two criteria for grammatical wordhood that we consider are a unit's free mobility and its internal immutability. These criteria also map to two cognitive mechanisms that could underlie successful statistical learning: learners might orient themselves around the low transitional probabilities at unit boundaries, or they might seek chunks with high internal transitional probabilities. We find that each criterion has its own facilitatory effect, and learning is best where they both align. This supports the battery‐of‐criteria approach to diagnosing wordhood, and also suggests that the mechanism behind statistical learning may not be a question of either/or; perhaps the two mechanisms do not compete, but mutually reinforce one another.
Acute cardiac autonomic and hemodynamic responses to resistive breathing: Effect of loading type and intensity
Authors: Pongpanit Karan , Korakot Manta , Nitilap Peerakan , Puplab Nopparat , Charususin Noppawan , Yuenyongchaiwat Kornanong
Published: March 2024

Objectives

This study aimed to assess the acute impact of distinct loading breathing types and intensities on cardiac autonomic function and hemodynamic responses in healthy young adults.

Methods

A randomized, crossover trial involved 28 participants who underwent inspiratory resistive breathing, expiratory resistive breathing (ERB) and combined resistive breathing, each at 30% and 60% of maximal respiratory pressures. Data on heart rate variability (HRV) and hemodynamic parameters were collected during each trial.

Results

The study revealed significant main and interaction effects for both the performed task and the intensity across all measured variables (all p < 0.001). ERB at 60% load demonstrated significantly higher HRV values in the standard deviation of normal‐to‐normal RR intervals, the square root of the mean squared difference of successive normal‐to‐normal RR intervals and high‐frequency power, as well as significantly lower values in heart rate, stroke volume, stroke volume index, cardiac output, cardiac index, end‐diastolic volume and end‐diastolic volume index, compared to other loaded protocols (all p < 0.001).

Conclusion

These findings highlight the acute effect of type‐specific and load‐dependent resistive breathing on cardiac autonomic and hemodynamic functions, where ERB at 60% intensity showed the most significant cardiovagal modulation while causing the least hemodynamic alterations.
SOX‐1 antibodies positive Lambert–Eaton myasthenic syndrome with occult small cell lung cancer: A case report
Authors: Zhao Liming , He Hongyan , Han Weixin , Meng Yizhe , Kang Lifei , Chen Yanqiang
Published: March 2024

Lambert–Eaton myasthenic syndrome (LEMS) is a rare paraneoplastic neurological syndrome of the neuromuscular transmission. The symptoms often progress slowly and can be misdiagnosed in early stage. Seropositive SOX‐1 antibodies are support for the diagnosis of LEMS and have high specificity for small cell lung cancer (SCLC). In this paper, we report a case of a 56‐year‐old man with smoking history who was admitted to hospital with progressive muscle weakness of the proximal legs. LEMS was diagnosed by repetitive nerve stimulation (RNS) testing and seropositive SOX‐1 antibodies. Primary screening with chest computed tomography (CT) and integrated PET/CT did not reveal any tumor. After continuous follow‐up, SCLC was found by chest CT and confirmed with pathological examination 10 months after the diagnosis of LEMS. Long‐term follow‐up and screening for occult SCLC in LEMS patients with positive SOX‐1 antibodies are very important.
First‐in‐human study of JNJ‐67571244, a CD33 × CD3 bispecific antibody, in relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome
Authors: Narayan Rupa , Piérola Ana Alfonso , Donnellan William B. , Yordi Antonieta Molero , Abdul‐Hay Maher , Platzbecker Uwe , Subklewe Marion , Kadia Tapan Mahendra , Alonso‐Domínguez Juan Manuel , McCloskey James , Bradford Kathryn , Curtis Martin , Daskalakis Nikki , Guttke Christina , Safer Karim , Hiebert Brett , Murphy Joseph , Li Xiang , Duchin Ken , Esteban Daniel
Published: March 2024

Relapsed/refractory (r/r) acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) outcomes remain poor. A targeted cluster of differentiation (CD)33 × CD3 bispecific antibody, JNJ‐67571244, was assessed to identify the maximum tolerated dose (MTD), recommended phase II dose (RP2D), safety and tolerability, and preliminary clinical activity in patients with r/rAML or r/rMDS. This first‐in‐human, open‐label, phase I, dose‐escalation/dose‐expansion study included patients with r/rAML or r/rMDS who were ineligible for or had exhausted standard therapeutic options. JNJ‐67571244 was administered intravenously or subcutaneously using step‐up dosing until ≥1 discontinuation condition was met. Outcomes included safety/tolerability, preliminary clinical activity, and systemic pharmacokinetics and pharmacodynamics. The study was terminated after evaluating 10 dose‐escalation cohorts (n = 68) and before starting dose‐expansion. Overall, 11 (16.2%) patients experienced ≥1 dose‐limiting toxicity; all experienced ≥1 treatment‐emergent adverse event (TEAE; treatment related: 60 [88.2%]); and 64 (94.1%) experienced ≥1 TEAE of Grade ≥3 toxicity (treatment related: 28 [41.2%]). Although some patients had temporary disease burden reductions, no responses were seen. JNJ‐67571244 administration increased multiple cytokines, which coincided with incidence of cytokine release syndrome, infusion‐related reactions, and elevated liver function tests. A prolonged step‐up strategy was tested to improve tolerability, though this approach did not prevent hepatotoxicity. T‐cell activation following treatment suggested target engagement but did not correlate with clinical activity. Safely reaching the projected exposure level for JNJ‐67571244 efficacy was not achieved, thus MTD and RP2D were not determined.
“Homo est deus”: Reflections on Luther's Christology
Authors: Vind Anna
Published: March 2024

In order to refresh scholarly discussions about Luther's Christology, his discourse on Christ is analyzed in the present article with reference to his humanist background and texts, where he attacks scholasticism, philosophy, and logic and seems to promote a new theological methodology and novel ways of speaking about Christ the man‐God.
Contextual predictors of self‐management and independence trajectories in adolescents and young adults with spina bifida
Authors: Ridosh Monique M. , Adams William , Payne Allison D. , Hilderbrand Taylor L. , Magaña Fabiola , Sawin Kathleen J. , Holmbeck Grayson N.
Published: March 2024

Aim

To examine socioeconomic, condition‐related, and neuropsychological predictors of self‐management trajectories in adolescents and young adults with spina bifida.

Method

In this longitudinal study, participants completed the Adolescent/Young Adult Self‐Management and Independence Scale interview. Socioeconomic status (SES), shunt status, lesion level, and executive functioning were assessed. Growth in self‐management was estimated using linear mixed‐effects models.

Results

Participants (n = 99) were aged 18 to 27 years. Approximately half (52.5%) were female and White; 15.2% were Black; and 32.3% Hispanic or Latino. Although none of the predictors were associated with growth in self‐management from ages 18 to 27 years (p > 0.05), several factors were associated with the intercept at age 18 years for total self‐management. Higher SES at baseline predicted a higher total self‐management score at age 18 years (b = 0.03, standard error [SE] = 0.01; p < 0.001). On average, participants at age 18 years with a shunt scored lower than those without a shunt (b = −0.90, SE = 0.32; p = 0.01); those with a thoracic lesion scored lower than those with lower lesion levels (lumbar: b = −1.22, SE = 0.34; sacral: b = −1.20, SE = 0.36; p = 0.001 for both). Better parent‐reported and teacher‐reported executive functions predicted higher total self‐management (metacognitive: b = −0.03, SE = 0.01; behavioral regulation: b = −0.04, SE = 0.01; p < 0.05 for both).

Interpretation

On average, all participants improved in self‐management over time. Additionally, baseline superiority in self‐management for adolescents and young adults without a shunt, less severe lesions, better executive functions, and higher SES persisted over time.

What this paper adds

Higher socioeconomic status at baseline predicted higher self‐management scores at age 18 years.

Participants with a shunt scored lower than those without a shunt.

Participants with a thoracic lesion scored lower than those with other, less severe lesions.

Better parent‐reported and teacher‐reported executive functions predicted higher self‐management scores at age 18 years.

Growth in self‐management was not moderated by socioeconomic, condition‐related, or neuropsychological variables.
The GPR40 novel agonist SZZ15‐11 improves non‐alcoholic fatty liver disease by activating the AMPK pathway and restores metabolic homeostasis in diet‐induced obese mice
Authors: Lei Lei , Gao Xuefeng , Zhai Jiayu , Liu Shuainan , Liu Quan , Li Caina , Cao Hui , Feng Cunyu , Chen Leilei , Lei Liran , Pan Xuan , Li Pingping , Liu Zhanzhu , Huan Yi , Shen Zhufang
Published: March 2024

Aim

Non‐alcoholic fatty liver is the most common cause of chronic liver disease. GPR40 is a potential therapeutic target for energy metabolic disorders. GPR40 is a potential therapeutic target for energy metabolic disorders. SZZ15‐11 is a newly synthesized GPR40 agonist. In this study, we estimate the potency of SZZ15‐11 in fatty liver treatment.

Methods

In vivo, diet‐induced obese (DIO) mice received SZZ15‐11 (50 mg/kg) and TAK875 (50 mg/kg) for 6 weeks. Blood glucose and lipid, hepatocyte lipid and liver morphology were analysed. In vitro, HepG2 cells and GPR40‐knockdown HepG2 cells induced with 0.3 mM oleic acid were treated with SZZ15‐11. Triglyceride and total cholesterol of cells were measured. At the same time, the AMPK pathway regulating triglycerides and cholesterol esters synthesis was investigated via western blot and quantitative polymerase chain reaction in both liver tissue and HepG2 cells.

Results

SZZ15‐11 was found to not only attenuate hyperglycaemia and hyperlipidaemia but also ameliorate fatty liver disease in DIO mice. At the same time, SZZ15‐11 decreased triglyceride and total cholesterol content in HepG2 cells. Whether examined in the liver of DIO mice or in HepG2 cells, SZZ15‐11 upregulated AMPKα phosphorylation and then downregulated the expression of the cholesterogenic key enzyme 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase and inhibited acetyl‐CoA carboxylase activity. Furthermore, SZZ15‐11 promotes AMPK activity via [cAMP]i accumulation.

Conclusion

This study confirmed that SZZ15‐11, a novel GPR40 agonist, improves hyperlipidaemia and fatty liver, partially via Gs signalling and the AMPK pathway in hepatocytes.
Cerebral amyloid angiopathy decades after red blood cell transfusions: a report of two cases from a prospective cohort
Authors: Kaushik K. , Wermer M. J. H. , van Etten E. S.
Published: March 2024

Background and purpose

Patients who underwent red blood cell (RBC) transfusion from donors who later developed multiple spontaneous intracerebral hemorrhages (ICHs) have recently been identified to have increased risk of ICH themselves. This increased risk of ICH was hypothesized to be related to iatrogenic cerebral amyloid angiopathy (iCAA) transmission. Two cases are presented who had RBC transfusion as an infant and presented with CAA at a relatively young age decades later.

Method

Cases were identified by prospectively asking all patients at our CAA outpatient clinic (November 2023 to January 2024) about a medical history with RBC transfusion or history with a high likelihood for RBC transfusion (e.g., hemolytic disease, trauma with massive hemorrhage). Eligible patients were all diagnosed with CAA, CAA with concomitant hypertensive arteriopathy or iCAA, and without hereditary CAA.

Results

Between November 2023 and January 2024, 2/35 (6%, 95% confidence interval 2%–19%) outpatient clinic patients had a history of RBC transfusion and none had a high likelihood medical history. The cases presented at age 47 and 57 and had already developed severe CAA.

Conclusions

Red blood cell transfusion might be a possible mechanism for iCAA; however, further prospective data collection and experimental evidence concerning blood transmission of amyloid‐β are needed.
Multiaxial fatigue life prediction using an improved Smith‐Watson‐Topper model
Authors: Li Jing , Shao Feng‐shan , He Zheng‐wei , Ma Juan , Qiu Yuan‐ying , Beer Michael
Published: March 2024

In this paper, the SWT model was improved by incorporating the Walker equation into the strain–life curve. The established model takes into account the material's sensitivity to mean stress by introducing the Walker exponent,w. Under uniaxial loading condition, the proposed model can reduce to the SWT model, Manson‐Coffin equation, and Walker model forwvalues of 0.5, 1, and 0, respectively. Under multiaxial symmetric loading, whenw = 0.5, the proposed model can be simplified as another SWT correction model (CXH) proposed by Chen et al. The prediction accuracy of the established model was validated using about 200 data points collected from literature. These data points were obtained from tests conducted on eight different kinds of metals under various multiaxial loading paths. The verification results indicate that 96.8% and 97.9% of the data points fall within the factor‐of‐three boundary for the loading paths without and with mean stresses, respectively.
Wetness severity increases abrupt shifts in ecosystem functioning in arid savannas
Authors: Vermeulen L. M. , Verbist B. , Van Meerbeek K. , Slingsby J. , Bernardino P. N. , Somers B.
Published: March 2024

The accelerating pace of climate change has led to unprecedented shifts in surface temperature and precipitation patterns worldwide, with African savannas being among the most vulnerable regions. Understanding the impacts of these extreme changes on ecosystem health, functioning and stability is crucial. This paper focuses on the detection of breakpoints, indicative of shifts in ecosystem functioning, while also determining relevant ecosystem characteristics and climatic drivers that increase susceptibility to these shifts within the semi‐arid to arid savanna biome. Utilising a remote sensing change detection approach and rain use efficiency (RaUE) as a proxy for ecosystem functioning, spatial and temporal patterns of breakpoints in the savanna biome were identified. We then employed a novel combination of survival analysis and remote sensing time series analysis to compare ecosystem characteristics and climatic drivers in areas experiencing breakpoints versus areas with stable ecosystem functioning. Key ecosystem factors increasing savanna breakpoint susceptibility were identified, namely higher soil sand content, flatter terrain and a cooler long‐term mean temperature during the wet summer season. Moreover, the primary driver of changes in ecosystem functioning in arid savannas, as opposed to wetter tropical savannas, was found to be the increased frequency and severity of rainfall events, rather than drought pressures. This research highlights the importance of incorporating wetness severity metrics alongside drought metrics to comprehensively understand climate–ecosystem interactions leading to abrupt shifts in ecosystem functioning in arid biomes. The findings also emphasise the need to consider the underlying ecosystem characteristics, including soil, topography and vegetation composition, in assessing ecosystem responses to climate change. While this research primarily concentrated on the southern African savanna as a case study, the methodological robustness of this approach enables its application to diverse arid and semi‐arid biomes for the assessment of climate–ecosystem interactions that contribute to abrupt shifts.
Ecosystem services at risk from disturbance in Europe's forests
Authors: Lecina‐Diaz Judit , Senf Cornelius , Grünig Marc , Seidl Rupert
Published: March 2024

Global change impacts on disturbances can strongly compromise the capacity of forests to provide ecosystem services to society. In addition, many ecosystem services in Europe are simultaneously provided by forests, emphasizing the importance of multifunctionality in forest ecosystem assessments. To address disturbances in forest ecosystem policies and management, spatially explicit risk analyses that consider multiple disturbances and ecosystem services are needed. However, we do not yet know which ecosystem services are most at risk from disturbances in Europe, where the respective risk hotspots are, nor which of the main disturbance agents are most detrimental to the provisioning of multiple ecosystem services from Europe's forests. Here, we quantify the risk of losing important ecosystem services (timber supply, carbon storage, soil erosion control and outdoor recreation) to forest disturbances (windthrows, bark beetle outbreaks and wildfires) in Europe on a continental scale. We find that up to 12% of Europe's ecosystem service supply is at risk from current disturbances. Soil erosion control is the ecosystem service at the highest risk, and windthrow is the disturbance agent posing the highest risk. Disturbances challenge forest multifunctionality by threatening multiple ecosystem services simultaneously on 19.8 Mha (9.7%) of Europe's forests. Our results highlight priority areas for risk management aiming to safeguard the sustainable provisioning of forest ecosystem services.
Association of pneumonia admission with polypharmacy and drug use in community‐dwelling older people
Authors: Hamaya Hironobu , Kojima Taro , Hattori Yukari , Akishita Masahiro
Published: March 2024

Aim

The purpose of the present study was to clarify the association of pneumonia admission with polypharmacy and specific drug use in community‐dwelling older people.

Methods

Using health insurance and long‐term care insurance data from Kure city in Japan, we retrospectively collected data for older community‐dwelling people (aged ≥65 years) from April 2017 to March 2019. The outcome was pneumonia admission. We carried out multivariate logistic regression analysis to identify the association of pneumonia admission with polypharmacy (≥5 drugs), the use of psychotropic drugs or anticholinergics with adjustment for patient backgrounds, such as comorbidity, and the daily life independence level for the older people with disability.

Results

Of 59 040 older people, 4017 (6.8%) participants were admitted for pneumonia in 2 years. The ratio of polypharmacy, and the use of psychotropic drugs and anticholinergics in the admission group were significantly higher than the non‐admission group. Multivariate logistic regression analysis showed that polypharmacy (odds ratio 1.29, 95% confidence interval 1.18–1.41), and the use of conventional antipsychotic drugs (odds ratio 1.39, 95% confidence interval 1.02–1.90), atypical antipsychotic drugs (odds ratio 1.67, 95% confidence interval 1.37–2.05) and anticholinergics (odds ratio 1.22, 95% confidence interval 1.13–1.33) were significantly associated with pneumonia admission.

Conclusion

The present results suggest that polypharmacy, and the use of psychotropic drugs and anticholinergics are risk factors for pneumonia admission. Geriatr Gerontol Int 2024; 24: 404–409.
Oral epithelial dysplasia with lymphocytic immune response: clinicopathological characterisation of 44 cases
Authors: Stojanov Ivan J , Omari Joud , Akeel Ibrahim , Sultan Ahmed S , Woo Sook‐Bin
Published: March 2024

Aims

Oral epithelial dysplasia (OED) often exhibits a lymphocytic/lichenoid immune response (LIR), imparting histological resemblance to lichenoid mucositis and rendering diagnosis challenging. The clinical appearances of OED and lichenoid inflammatory processes are generally divergent, presenting as well‐demarcated hyperkeratotic plaques and diffuse white and/or red mucosal change with variably prominent Wickham striae, respectively. To date, clinicopathological characterisation of OED with LIR, including clinical/gross appearance, has not been depicted.

Methods and results

Cases of solitary OED with LIR for which a clinical photograph was available were identified in the authors’ institutional files. Clinical and histological features were documented. In 44 identified cases, dysplasia was mild (19 of 44, 43.2%), moderate (19 of 44, 43.2%) and severe (six of 44, 13.6%). Clinically/grossly, all 44 cases (100.0%), presented as well‐demarcated hyperkeratotic plaques lacking diffuse white‐and‐red mucosal change or Wickham striae. Histologically, OED with LIR exhibited numerous ‘lichenoid’ features beyond the lymphocytic band in the superficial lamina propria, including: leucocyte transmigration (38 of 44, 86.4%), spongiosis (37 of 44, 84.1%), Civatte/colloid bodies (36 of 44, 81.8%), basal cell degeneration (29 of 45, 65.9%), sawtooth rete ridges (11 of 44, 25.0%) and subepithelial clefting (7 of 44, 15.9%).

Conclusions

Virtually any lichenoid histological feature may be seen in OED with LIR, representing a significant diagnostic pitfall. The typical clinical appearance of OED with LIR is of a well‐demarcated hyperkeratotic plaque, characteristic of keratinising dysplasia and devoid of lichenoid features. This suggests that pathologist access to clinical photographs during diagnostic interpretation of biopsied white lesions, which represents opportunity to perform gross examination of the disease process, may reduce interobserver variability and improve diagnostic accuracy in this challenging differential diagnosis.
Language dynamics and agency in multilingual research interviews
Authors: Svensson Hanna
Published: March 2024

In a world of increasing linguistic diversity, questions of language use and language ideologies in research interviews are gaining increasing importance. This article reports and reflects on language use in research interviews with former refugees in New Zealand and Sweden. In the interviews, multilingual speakers had the option to engage in the host language (English or Swedish, respectively), to bring their own language support person, or to request a professional interpreter. The article suggests that providing these options enabled participants to engage a greater range of linguistic and multimodal resources to create meaning and construct their identities, and also provided opportunities for language learning in the interviews. The article also highlights the importance of acknowledging the role of interpreters in the co‐construction of meaning and what this means for data collection and findings.
Enzyme‐assisted extraction of rapeseed oil with minimum water addition: a proof‐of‐concept study
Authors: Thomsen Kristian , Raak Norbert , Gregersen Sandra Beyer , Månsson Lars , Miquel Becker Eleonora
Published: March 2024

The increased demand for vegetable oils calls for new strategies for enhancing the yield of mechanical oil extraction, preferably without the use of potentially hazardous solvents such as n‐hexane. Enzyme‐assisted oil extraction has been studied under aqueous conditions, where the oil recovery was enhanced due to the partial enzymatic breakdown of cell wall compounds. However, this process is often not feasible for industrial applications, where mechanical pressing of dry seeds is implemented. This study provides a proof‐of‐concept for enzyme‐assisted rapeseed oil extraction with minimum water addition (1 mL per 100 g rapeseeds). The application of cellulytic and pectolytic enzymes increased the reducing sugar content as a result of the carbohydrate breakdown. The oil recovery in the mechanical pressing was increased significantly from ~60% to ~65%, and the quality of the oils was not significantly affected by the enzyme treatment.
Impact of digital technologies on the risk assessment in food supply chain: a wake towards digitalisation
Authors: Sharma Janpriy , Tyagi Mohit , Kazançoğlu Yiğit
Published: March 2024

Nowadays, the adoption of digital technologies getting a significant pace. It has the potential to improve the existing dynamics of the food supply chains and improve its transparency. Many times, uncertainties prevail in the food supply chain performance systems, which cause amplification of risk. These uncertainties are due to a lack of product traceability mechanisms in the food supply chains. Hence, it becomes vital to harness the potential of digital technologies like the Internet of Things, Blockchain, and common digital platforms to improve the flow of information and products in the food supply chain. The presented work is aimed at assessing the impact of digital technologies on risk identification and its mitigation in the food supply chain dynamics. For the same, risks are assessed relative to its mitigation strategy by the two‐stage methodology of preference rating approach. Here, the impacts of risk under consideration are quantified relative to every risk mitigation strategy for a better depiction of the potential of digital transformation of the food supply chain. It yields the broadening of its implication perspectives at operational, strategic and tactical levels of the food supply chain and makes them future‐ready.