bluuebunny/crossref_metadata_2025 huggingface dataset:
Antiphospholipid antibodies as potential predictors of disease severity and poor prognosis in systemic lupus erythematosus-associated thrombocytopenia: results from a real-world CSTAR cohort study
Authors: Li Jun , Peng Liying , Wu Lijun , Ding Yufang , Duan Xinwang , Xu Jian , Wei Wei , Chen Zhen , Zhao Cheng , Yang Min , Jiang Nan , Zhang Shangzhu , Wang Qian , Tian Xinping , Li Mengtao , Zeng Xiaofeng , Zhao Yan , Zhao Jiuliang
Published: March 2024

Background

To investigate the role of antiphospholipid antibodies (aPLs) in the disease severity and prognosis of SLE-related thrombocytopenia (SLE-TP).

Methods

This multicenter prospective study was conducted based on data from the CSTAR registry. TP was defined as a platelet count<100 × 109/L. Demographic characteristics, platelet count, clinical manifestations, disease activity, and autoantibody profiles were collected at baseline. Relapse was defined as the loss of remission. Bone marrow aspirate reports were also collected.

Results

A total of 350 SLE-TP patients with complete follow-up data, 194 (55.4%) were aPLs positive. At baseline, SLE-TP patients with aPLs had lower baseline platelet counts (61.0 × 109/L vs. 76.5 × 109/L, P<0.001), and a higher proportion of moderate to severe cases (24.2% vs. 14.1% ; 18.0% vs. 8.3%, P<0.001). SLE-TP patients with aPLs also had lower platelet counts at their lowest point (37.0 × 109/L vs. 51.0 × 109/L, P = 0.002). In addition, thean increasing number of aPLs types was associated with a decrease in the baseline and minimum values of platelets ( P<0.001, P = 0.001). During follow-up, SLE-TP carrying aPLs had a higher relapse rate (58.2% vs. 44.2%, P = 0.009) and a lower complete response (CR) rate. As the types of aPLs increased, the relapse rate increased, and the CR rate decreased. Furthermore, there was no significant difference in the ratio of granulocytes to red blood cells (G/E), the total number of megakaryocyte and categories.

Conclusion

SLE-TP patients with positive aPLs had more severe disease a lower remission rate but a higher relapse rate.
Evidence of brain metabolism redistribution from neocortex to primitive brain structures in early acute COVID-19 respiratory syndrome
Authors: Souza Stephan P. M. , Colet Nicoli , Fujiwara Mariana , Fernandes Alins P. , Tobar Natalia , Dertkigil Sergio S. J. , Takahashi Maria Emilia S. , Amorim Bárbara J. , Silva Lucas S. , Yasuda Clarissa L. , Cendes Fernando , de Souza Thiago F. , Rodrigues Juliano T. , Zantut-Wittmann Denise E. , Ramos Celso Dario
Published: March 2024

Background

Neuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms.

Results

Twenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4–20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (< 2 SD) was observed in up to a third of patients. Associations were found between hypoxia, inflammation, coagulation markers, and [18F]FDG uptake in various brain structures.

Conclusions

Brain metabolism is clearly affected during the acute phase of COVID-19 respiratory syndrome in neurologically asymptomatic or oligosymptomatic patients. The most frequent finding is marked hypermetabolism in evolutionary ancient structures such as lenticular nucleus and thalami. Neocortical metabolism was reduced in up to one third of patients, suggesting a redistribution of brain metabolism from the neocortex to evolutionary ancient brain structures in these patients.
Elevation affects both the occurrence of ungulate browsing and its effect on tree seedling growth for four major tree species in European mountain forests
Authors: Bernard Marianne , Barrere Julien , Morin Xavier , Saïd Sonia , Boulanger Vincent , Granda Elena , Benavides Raquel , Jactel Hervé , Heurich Marco , Rabasa Sonia G. , Valladares Fernando , Kunstler Georges
Published: March 2024

Key message

In European mountain forests, the growth of silver fir (Abies alba Mill.), sycamore maple (Acer pseudoplatanus L.), European beech (Fagus sylvatica L.) and Norway spruce (Picea abies (L.) H. Karst.) seedlings is more strongly affected by ungulate browsing than by elevation. But, the constraint exerted by ungulates, in particular the probability for seedlings to be browsed, increases with elevation for most species.

Context

While concerns about mountain forest regeneration rise due to their high vulnerability to climate change, the increase in wild ungulate populations and the expansion of their range in the last decades exert an additional constraint on the survival and growth of young trees. Understanding how this constraint can vary with elevation is thus a key to assess the consequences of this population increase for the regeneration of mountain forests.

Aims

In this study, we investigate the effect of elevation on (i) the occurrence of browsing for seedlings and on (ii) the reduction in seedling growth induced by ungulate browsing.

Methods

We monitored height growth and browsing occurrence on silver fir, sycamore maple, European beech and Norway spruce seedlings across seven elevation gradients (from 400 to 2013 m) located from France to northern Sweden.

Results

Seedlings of the two most palatable species—fir and maple—were more likely to be browsed at high elevation while the opposite effect was observed for spruce. Browsing strongly reduced seedling growth for all species but Norway spruce, while elevation had no direct effect on seedling growth. This browsing-induced growth reduction was stronger at high elevation for fir seedlings.

Conclusions

Browsing is overall a stronger constraint on seedling growth than elevation for four dominant species of European mountain forests. Elevation can, however, affect both browsing probability and the effect of browsing on seedling growth. Our results highlight the importance of taking into account ungulate pressure and its interactive effect with elevation when forecasting the regeneration of mountain forests under a changing climate.
Hypoxia-induced circRNAs encoded by PPARA are highly expressed in human cardiomyocytes and are potential clinical biomarkers of acute myocardial infarction
Authors: Huang Shasha , Wu Zhangying , Zhou Yang
Published: March 2024

Background

Acute myocardial infarction (AMI) is a serious cardiovascular disease that adversely affects human health. Circular RNAs (circRNAs) are involved in the pathological and physiological processes of AMI, but the biological mechanism of their involvement and their clinical significance remain unknown. We aimed to identify circRNAs that are significantly associated with morbidity in the peripheral blood of patients with AMI and evaluate their diagnostic utility.

Methods

High-throughput sequencing was used to screen for differentially expressed circRNAs in peripheral blood samples obtained from five patients with AMI and five sex- and age-matched healthy controls. A series of bioinformatics tools and databases were used to determine the biological functional classification and pathway enrichment of the circRNAs based on data obtained from sequencing. A hypoxia model was established and used to evaluate the effect of hypoxia on circRNA expression in human cardiomyocytes. A cytoplasmic separation assay and enzyme resistance assay were employed to identify the biological characteristics of circRNA. Polymerase chain reaction validity testing and receiver operating characteristic (ROC) curve analysis were used to evaluate the utility of circRNA assessments in the diagnosis of AMI.

Results

A large number of circRNAs were found to be differentially expressed in the peripheral blood of patients with AMI, and significantly more of these circRNAs were highly expressed than lowly expressed. The genes encoding these circRNAs have a wide range of effects on various functions in the body. A hypoxic environment promoted the upregulation of circRNA expression in human cardiomyocytes, and hsa_circ_0116795 encoded by PPARA was highly expressed in the peripheral blood of the patients with AMI. In terms of biological characteristics, under physiological conditions, hsa_circ_0116795 (circ_PPARA) was mainly located in the cytoplasm of cardiomyocytes and found to be resistant to exonuclease. The ROC curve analysis showed that the expression levels of circ_PPARA in the peripheral blood of patients with AMI were significantly different from those in the peripheral blood of healthy controls.

Conclusion

A large number of abnormally expressed circRNAs are detectable in the peripheral blood of patients with AMI. In particular, circ_PPARA is highly expressed in human myocardial cells under hypoxic conditions, and its biological characteristics indicate that it could be employed as a biomarker for the early diagnosis of AMI.
Perturbation and resilience of the gut microbiome up to 3 months after β-lactams exposure in healthy volunteers suggest an important role of microbial β-lactamases
Authors: d’Humières Camille , Delavy Margot , Alla Laurie , Ichou Farid , Gauliard Emilie , Ghozlane Amine , Levenez Florence , Galleron Nathalie , Quinquis Benoit , Pons Nicolas , Mullaert Jimmy , Bridier-Nahmias Antoine , Condamine Bénédicte , Touchon Marie , Rainteau Dominique , Lamazière Antonin , Lesnik Philippe , Ponnaiah Maharajah , Lhomme Marie , Sertour Natacha , Devente Savannah , Docquier Jean-Denis , Bougnoux Marie-Elisabeth , Tenaillon Olivier , Magnan Mélanie , Ruppé Etienne , Grall Nathalie , Duval Xavier , Ehrlich Dusko , Mentré France , Denamur Erick , Rocha Eduardo P. C. , Le Chatelier Emmanuelle , Burdet Charles ,   for the PrediRes study group
Published: March 2024

Background

Antibiotics notoriously perturb the gut microbiota. We treated healthy volunteers either with cefotaxime or ceftriaxone for 3 days, and collected in each subject 12 faecal samples up to day 90. Using untargeted and targeted phenotypic and genotypic approaches, we studied the changes in the bacterial, phage and fungal components of the microbiota as well as the metabolome and the β-lactamase activity of the stools. This allowed assessing their degrees of perturbation and resilience.

Results

While only two subjects had detectable concentrations of antibiotics in their faeces, suggesting important antibiotic degradation in the gut, the intravenous treatment perturbed very significantly the bacterial and phage microbiota, as well as the composition of the metabolome. In contrast, treatment impact was relatively low on the fungal microbiota. At the end of the surveillance period, we found evidence of resilience across the gut system since most components returned to a state like the initial one, even if the structure of the bacterial microbiota changed and the dynamics of the different components over time were rarely correlated. The observed richness of the antibiotic resistance genes repertoire was significantly reduced up to day 30, while a significant increase in the relative abundance of β-lactamase encoding genes was observed up to day 10, consistent with a concomitant increase in the β-lactamase activity of the microbiota. The level of β-lactamase activity at baseline was positively associated with the resilience of the metabolome content of the stools.

Conclusions

In healthy adults, antibiotics perturb many components of the microbiota, which return close to the baseline state within 30 days. These data suggest an important role of endogenous β-lactamase-producing anaerobes in protecting the functions of the microbiota by de-activating the antibiotics reaching the colon.
Biofilm colonization and succession in a full-scale partial nitritation-anammox moving bed biofilm reactor
Authors: Suarez Carolina , Rosenqvist Tage , Dimitrova Ivelina , Sedlacek Christopher J. , Modin Oskar , Paul Catherine J. , Hermansson Malte , Persson Frank
Published: March 2024

Background

Partial nitritation-anammox (PNA) is a biological nitrogen removal process commonly used in wastewater treatment plants for the treatment of warm and nitrogen-rich sludge liquor from anaerobic digestion, often referred to as sidestream wastewater. In these systems, biofilms are frequently used to retain biomass with aerobic ammonia-oxidizing bacteria (AOB) and anammox bacteria, which together convert ammonium to nitrogen gas. Little is known about how these biofilm communities develop, and whether knowledge about the assembly of biofilms in natural communities can be applied to PNA biofilms.

Results

We followed the start-up of a full-scale PNA moving bed biofilm reactor for 175 days using shotgun metagenomics. Environmental filtering likely restricted initial biofilm colonization, resulting in low phylogenetic diversity, with the initial microbial community comprised mainly of Proteobacteria. Facilitative priority effects allowed further biofilm colonization, with the growth of initial aerobic colonizers promoting the arrival and growth of anaerobic taxa like methanogens and anammox bacteria. Among the early colonizers were known ‘oligotrophic’ ammonia oxidizers including comammox Nitrospira and Nitrosomonas cluster 6a AOB. Increasing the nitrogen load in the bioreactor allowed colonization by ‘copiotrophic’ Nitrosomonas cluster 7 AOB and resulted in the exclusion of the initial ammonia- and nitrite oxidizers.

Conclusions

We show that complex dynamic processes occur in PNA microbial communities before a stable bioreactor process is achieved. The results of this study not only contribute to our knowledge about biofilm assembly and PNA bioreactor start-up but could also help guide strategies for the successful implementation of PNA bioreactors.
Identifying structural risk factors for overdose following incarceration: a concept mapping study
Authors: Nall Samantha K. , Jurecka Cole , Ammons Anthony , Rodriguez Avel , Craft Betsy , Waleed Craig , Dias Daniel , Henderson Jessie , Boyer Joshua , Yamkovoy Kristina , Swathi Pallavi Aytha , Patil Prasad , Behne Forrest , LeMasters Katherine , Brinkley-Rubinstein Lauren , Barocas Joshua A.
Published: March 2024

Background

Currently, there are more than two million people in prisons or jails, with nearly two-thirds meeting the criteria for a substance use disorder. Following these patterns, overdose is the leading cause of death following release from prison and the third leading cause of death during periods of incarceration in jails. Traditional quantitative methods analyzing the factors associated with overdose following incarceration may fail to capture structural and environmental factors present in specific communities. People with lived experiences in the criminal legal system and with substance use disorder hold unique perspectives and must be involved in the research process.

Objective

To identify perceived factors that impact overdose following release from incarceration among people with direct criminal legal involvement and experience with substance use.

Methods

Within a community-engaged approach to research, we used concept mapping to center the perspectives of people with personal experience with the carceral system. The following prompt guided our study: “What do you think are some of the main things that make people who have been in jail or prison more and less likely to overdose?” Individuals participated in three rounds of focus groups, which included brainstorming, sorting and rating, and community interpretation. We used the Concept Systems Inc. platform groupwisdom for our analyses and constructed cluster maps.

Results

Eight individuals (ages 33 to 53) from four states participated. The brainstorming process resulted in 83 unique factors that impact overdose. The concept mapping process resulted in five clusters: (1) Community-Based Prevention, (2) Drug Use and Incarceration, (3) Resources for Treatment for Substance Use, (4) Carceral Factors, and (5) Stigma and Structural Barriers.

Conclusions

Our study provides critical insight into community-identified factors associated with overdose following incarceration. These factors should be accounted for during resource planning and decision-making.
Experiences and concerns of parents of children with a 16p11.2 deletion or duplication diagnosis: a reflexive thematic analysis
Authors: Butter Charlotte E. , Goldie Caitlin L. , Hall Jessica H. , Leadbitter Kathy , Burkitt Emma M.M. , van den Bree Marianne B.M. , Green Jonathan M.
Published: March 2024

Background

16p11.2 proximal deletion and duplication syndromes (Break points 4–5) (593KB, Chr16; 29.6-30.2mb - HG38) are observed to have highly varied phenotypes, with a known propensity for lifelong psychiatric problems. This study aimed to contribute to a research gap by qualitatively exploring the challenges families with 16p11.2 deletion and duplication face by answering three research questions: (1) What are parents’ perceptions of the ongoing support needs of families with children who have 16p11.2 living in the UK?; (2) What are their experiences in trying to access support?; (3) In these regards, do the experiences of parents of children with duplication converge or vary from those of parents of children with 16p11.2 deletion?

Methods

33 parents with children (aged 7–17 years) with 16p11.2 deletion or duplication participated in structured interviews, including the Autism Diagnostic Interview– Revised (ADI-R). Their answers to the ADI-R question ‘what are your current concerns’ were transcribed and subsequently analysed using Braun and Clarke’s six step reflexive thematic analysis framework.

Results

Three themes were identified: (1) Child is Behind Peers (subthemes: developmentally; academically; socially; emotionally); (2) Metabolism and Eating Patterns and; (3) Support (subthemes: insufficient support available; parent has to fight to access support; COVID-19 was a barrier to accessing support; 16p11.2 diagnosis can be a barrier to support, child is well-supported).

Conclusions

Parents of children with either 16p11.2 deletion or duplication shared similar experiences. However, metabolism concerns were specific to parents of children with 16p11.2 deletion. The theme Child is Behind Peers echoed concerns raised in previous Neurodevelopmental Copy Number Variant research. However, there were some key subthemes relating to research question (2) which were specific to this study. This included parents’ descriptions of diagnostic overshadowing and the impact of a lack of eponymous name and scant awareness of 16p11.2.
Endophilin A2 controls touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking
Authors: Xie Man-Xiu , Lai Ren-Chun , Xiao Yi-Bin , Zhang Xi , Cao Xian-Ying , Tian Xiao-Yu , Chen An-Nan , Chen Zi-Yi , Cao Yan , Li Xiao , Zhang Xiao-Long
Published: March 2024

Background

Tactile and mechanical pain are crucial to our interaction with the environment, yet the underpinning molecular mechanism is still elusive. Endophilin A2 (EndoA2) is an evolutionarily conserved protein that is documented in the endocytosis pathway. However, the role of EndoA2 in the regulation of mechanical sensitivity and its underlying mechanisms are currently unclear.

Methods

Male and female C57BL/6 mice (8–12 weeks) and male cynomolgus monkeys (7–10 years old) were used in our experiments. Nerve injury-, inflammatory-, and chemotherapy-induced pathological pain models were established for this study. Behavioral tests of touch, mechanical pain, heat pain, and cold pain were performed in mice and nonhuman primates. Western blotting, immunostaining, co-immunoprecipitation, proximity ligation and patch-clamp recordings were performed to gain insight into the mechanisms.

Results

The results showed that EndoA2 was primarily distributed in neurofilament-200-positive (NF200+) medium-to-large diameter dorsal root ganglion (DRG) neurons of mice and humans. Loss of EndoA2 in mouse NF200+ DRG neurons selectively impaired the tactile and mechanical allodynia. Furthermore, EndoA2 interacted with the mechanically sensitive ion channel Piezo2 and promoted the membrane trafficking of Piezo2 in DRG neurons. Moreover, as an adaptor protein, EndoA2 also bound to kinesin family member 5B (KIF5B), which was involved in the EndoA2-mediated membrane trafficking process of Piezo2. Loss of EndoA2 in mouse DRG neurons damaged Piezo2-mediated rapidly adapting mechanically activated currents, and re-expression of EndoA2 rescued the MA currents. In addition, interference with EndoA2 also suppressed touch sensitivity and mechanical hypersensitivity in nonhuman primates.

Conclusions

Our data reveal that the KIF5B/EndoA2/Piezo2 complex is essential for Piezo2 trafficking and for sustaining transmission of touch and mechanical hypersensitivity signals. EndoA2 regulates touch and mechanical allodynia via kinesin-mediated Piezo2 trafficking in sensory neurons. Our findings identify a potential new target for the treatment of mechanical pain.
Unsupervised deep-learning framework for 5D seismic denoising and interpolation
Authors: Saad Omar M. , Helmy Islam , Chen Yangkang
Published: March 2024

We develop an unsupervised framework to reconstruct missing data from noisy and incomplete five-dimensional (5D) seismic data. Our method comprises two main components: a deep-learning network and the projection onto the convex sets (POCS) method. The model works iteratively, passing the data between the two components and splitting the data into a group of patches. The developed deep-learning model is inspired by the transformer architecture, wherein the extracted patches are flattened, and an embedded layer (fully connected layer) is used to transform the 1D flattened vector into the feature latent space. Afterward, an attention network is used to highlight the important information within these features, which improves the denoising performance of the deep-learning model. Furthermore, we use several skip connections between the fully connected layers to enhance the learning capability of the network. Next, the output of the POCS algorithm is considered the input of the deep-learning model for the following iteration. The developed model iteratively works in an unsupervised scheme wherein labeled data are not required. A performance comparison with benchmark methods using several synthetic and field examples shows that our method outperforms the traditional methods.
Prediction of Cancer Symptom Trajectory Using Longitudinal Electronic Health Record Data and Long Short-Term Memory Neural Network
Authors: Chae Sena , Street W. Nick , Ramaraju Naveenkumar , Gilbertson-White Stephanie
Published: March 2024

PURPOSE

Ability to predict symptom severity and progression across treatment trajectories would allow clinicians to provide timely intervention and treatment planning. However, such predictions are difficult because of sparse and inconsistent assessment, and simplistic measures such as the last observed symptom severity are often used. The purpose of this study is to develop a model for predicting future cancer symptom experiences on the basis of past symptom experiences.

PATIENTS AND METHODS

We performed a retrospective, longitudinal analysis using records of patients with cancer (n = 208) hospitalized between 2008 and 2014. A long short-term memory (LSTM)–based recurrent neural network, a linear regression, and random forest models were trained on previous symptoms experienced and used to predict future symptom trajectories.

RESULTS

We found that at least one of three tested models (LSTM, linear regression, and random forest) outperform predictions based solely on the previous clinical observation. LSTM models significantly outperformed linear regression and random forest models in predicting nausea ( P < .1) and psychosocial status ( P < .01). Linear regression outperformed all models when predicting oral health ( P < .01), while random forest outperformed all models when predicting mobility ( P < .01) and nutrition ( P < .01).

CONCLUSION

We can successfully predict patients' symptom trajectories with a prediction model, built with sparse assessment data, using routinely collected nursing documentation. The results of this project can be applied to better individualize symptom management to support cancer patients' quality of life.
Prognostic Impact of Prostate-Specific Antigen at 6 Months After Radiotherapy in Localized Prostate Cancer: An Individual Patient Data Analysis of Randomized Trials
Authors: Kwak Lucia , Ravi Praful , Armstrong John G. , Beckendorf Veronique , Chin Joseph L. , D'Amico Anthony V. , Dearnaley David P. , Di Stasi Savino M. , Gillessen Silke , Lukka Himanshu , Mottet Nicolas , Pommier Pascal , Seiferheld Wendy , Sydes Matthew R. , Tombal Bertrand , Zapatero Almudena , Regan Meredith M. , Xie Wanling , Sweeney Christopher J.
Published: March 2024

PURPOSE

We sought to evaluate the prognostic impact of prostate-specific antigen (PSA) at 6 months after completion of radiotherapy (RT) in patients treated with RT alone, RT plus short-term (st; 3-6 months), and RT plus long-term (lt; 24-36 months) androgen-deprivation therapy (ADT).

PATIENTS AND METHODS

Individual patient data were obtained from 16 randomized trials evaluating RT ± ADT for localized prostate cancer (PCa) between 1987 and 2011. The lowest PSA recorded within 6 months after RT completion was identified and categorized as < or ≥0.1 ng/mL. The primary outcomes were metastasis-free survival (MFS), PCa-specific mortality (PCSM), and overall survival (OS), from 12 months after random assignment.

RESULTS

Ninety-eight percent (n = 2,339/2,376) of patients allocated to RT alone, 84% (n = 4,756/5,658) allocated to RT + stADT, and 77% (n = 1,258/1,626) allocated to RT + ltADT had PSA ≥0.1 ng/mL within 6 months after completing RT. PSA ≥0.1 ng/mL was associated with lower MFS and OS and higher PCSM among patients allocated to RT ± ADT (RT – MFS: hazard ratio [HR], 2.24 [95% CI, 1.21 to 4.16]; PCSM: subdistribution hazard ratio [sHR], 1.82 [0.51 to 6.49]; OS: HR, 1.72 [0.97 to 3.05]; RT + stADT – MFS: HR, 1.27 [1.12 to 1.44]; PCSM: sHR, 2.10 [1.52 to 2.92]; OS: HR, 1.26 [1.11 to 1.44]; RT + ltADT – MFS: HR, 1.58 [1.27 to 1.96]; PCSM: sHR, 1.97 [1.11 to 3.49]; OS: HR, 1.59 [1.27 to 1.99]). Five-year MFS rates among patients allocated to RT, RT + stADT, and RT + ltADT were 91% versus 79%, 83% versus 76%, and 87% versus 74%, respectively, based on PSA < or ≥0.1 ng/mL.

CONCLUSION

PSA ≥0.1 ng/mL within 6 months after RT completion was prognostic for lt outcomes in patients treated with RT ± ADT for localized PCa. This can be used to counsel patients treated with RT ± ADT and in guiding clinical trial design evaluating novel systemic therapies with RT + ADT as well as (de)intensification strategies.
European Stop Tyrosine Kinase Inhibitor Trial (EURO-SKI) in Chronic Myeloid Leukemia: Final Analysis and Novel Prognostic Factors for Treatment-Free Remission
Authors: Mahon Francois-Xavier , Pfirrmann Markus , Dulucq Stéphanie , Hochhaus Andreas , Panayiotidis Panayiotis , Almeida Antonio , Mayer Jiri , Hjorth-Hansen Henrik , Janssen Jeroen J.W.M. , Mustjoki Satu , Martinez-Lopez Joaquin , Vestergaard Hanne , Ehrencrona Hans , Machová Poláková Katerina , Olsson-Strömberg Ulla , Ossenkoppele Gert , Berger Marc G. , Etienne Gabriel , Dengler Jolanta , Brümmendorf Tim H. , Burchert Andreas , Réa Delphine , Rousselot Philippe , Nicolini Franck E. , Hofmann Wolf-Karsten , Richter Johan , Saussele Susanne ,   on behalf of the EURO-SKI Investigators, Mayer Jiri , Voglová Jaroslava , Faber Edgar , Klamova Hana , Vestergaard Hanne , Koskenvesa Perttu , Mahon Francois-Xavier , Etienne Gabriel , Berger Marc G. , Rousselot Philippe , Nicolini Franck E. , Charbonnier Aude , Legros Laurence , Réa Delphine , Guilhot François , Escoffre-Barbe Martine , Huguet Françoise , Gyan Emmanuel , Brümmendorf Tim Henrik , Waller Cornelius , Dengler Jolanta , Hochhaus Andreas , Saußele Susanne , Burchert Andreas , Kunzmann Volker , Pagoni Maria N. , Panayiotidis Panayiotis , Janssen Jeroen J.W.M. , Ossenkoppele Gert , Westerweel Peter E. , de Greef Georgine E. , Gruber Franz , Hjorth-Hansen Henrik , Almeida Antonio , Martinez-Lopez Joaquin , Lotfi Kourosh , Richter Johan , Stenke Leif , Olsson-Strömberg Ulla , Söderlund Stina
Published: March 2024

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.

The European Stop Kinase Inhibitors (EURO-SKI) study is the largest clinical trial for investigating the cessation of tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia in stable deep molecular remission (DMR). Among 728 patients, 434 patients (61%; 95% CI, 57 to 64) remained in major molecular response (MMR) at 6 months and 309 patients of 678 (46%; 95% CI, 42 to 49) at 36 months. Duration of TKI treatment and DMR before TKI stop were confirmed as significant factors for the prediction of MMR loss at 6 months. In addition, the type of BCR::ABL1 transcript was identified as a prognostic factor. For late MMR losses after 6 months, TKI treatment duration, percentage of blasts in peripheral blood, and platelet count at diagnosis were significant factors in multivariate analysis. For the entire study period of 36 months, multiple logistic regression models confirmed duration of treatment, blasts, and transcript type as independent factors for MMR maintenance. In addition to the duration of treatment, transcript type as well as blasts in peripheral blood at diagnosis should be considered as important factors to predict treatment-free remission.
Lower Prevalence of Diabetic Ketoacidosis at Diagnosis in Research Participants Monitored for Hyperglycemia
Authors: Sooy Morgan , Pyle Laura , Alonso Guy Todd , Broncucia Hali C , Rewers Arleta , Gottlieb Peter A , Simmons Kimber M , Rewers Marian J , Steck Andrea K
Published: March 2024

Context

In Colorado children, the prevalence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes has been increasing over time.

Objective

To evaluate the prevalence of and factors involved in DKA at type 1 diabetes diagnosis among participants followed in monitoring research studies before diagnosis compared to patients from the community.

Methods

We studied patients < 18 years diagnosed with type 1 diabetes between 2005 and 2021 at the Barbara Davis Center for Diabetes and compared the prevalence of and factors associated with DKA at diagnosis among participants in preclinical monitoring studies vs those diagnosed in the community.

Results

Of 5049 subjects, 164 were active study participants, 42 inactive study participants, and 4843 were community patients. Active study participants, compared to community patients, had lower HbA1c (7.3% vs 11.9%; P < .001) and less frequently experienced DKA (4.9% vs 48.5%; P < .001), including severe DKA (1.2% vs 16.2%; P < .001). Inactive study participants had intermediate levels for both prevalence and severity of DKA. DKA prevalence increased in community patients, from 44.0% to 55%, with less evidence for a temporal trend in study participants. DKA prevalence was highest in children < 2 years (13% in active study participants vs 83% in community patients). In community patients, younger age (P = .0038), public insurance (P < .0001), rural residence (P < .0076), higher HbA1c (P < .0001), and ethnicity minority status (P < .0001) were associated with DKA at diagnosis.

Conclusion

While DKA prevalence increases in community patients over time, it stayed < 5% in active research participants, who have a 10 times lower prevalence of DKA at diagnosis, including among minorities.
Research Note: New Evidence on the Motherhood Wage Penalty
Authors: Yu Wei-hsin , Kuo Janet Chen-Lan
Published: March 2024

U.S. women's age at first birth has increased substantially. Yet, little research has considered how this changing behavior may have affected the motherhood pay penalty, or the wage decrease with a child's arrival, experienced by the current generation. Using Rounds 1–19 of the National Longitudinal Survey of Youth 1997 (NLSY97), in this research note we examine shifts in hourly pay with childbirth for a cohort of women who became mothers mostly in the 2000s and 2010s. Results from fixed-effects models indicate that the motherhood pay penalty for NLSY97 women who had their first child before their late 20s is generally similar to that of previous cohorts. Those who became mothers near or after age 30, however, encounter a parenthood premium, as men do. The growing proportion of women delaying motherhood, coupled with the rising heterogeneity in motherhood wage outcomes by childbearing timing, contributes to a comparatively small motherhood penalty for this recent cohort. The pay advantage of “late mothers” cannot be explained by factors such as their labor market locations, number of children, stage of childrearing, marital status, or ethnoracial composition. Instead, the hourly gain stems from such mothers’ tendency to reduce working hours more than other mothers without experiencing a commensurate decrease in total pay. Unlike the fatherhood premium, the premium for late mothers does not lead to a real boost in income.
Higher Postoperative Mortality and Inferior Survival After Right-Sided Liver Resection for Perihilar Cholangiocarcinoma: Left-Sided Resection is Preferred When Possible
Authors: Olthof Pim B. , Erdmann Joris I. , Alikhanov Ruslan , Charco Ramón , Guglielmi Alfredo , Hagendoorn Jeroen , Hakeem Abdul , Hoogwater Frederik J. H. , Jarnagin William R. , Kazemier Geert , Lang Hauke , Maithel Shishir K. , Malago Massimo , Malik Hassan Z. , Nadalin Silvio , Neumann Ulf , Olde Damink Steven W. M. , Pratschke Johann , Ratti Francesca , Ravaioli Matteo , Roberts Keith J. , Schadde Erik , Schnitzbauer Andreas A. , Sparrelid Ernesto , Topal Baki , Troisi Roberto I. , Groot Koerkamp Bas ,   Perihilar Cholangiocarcinoma Collaboration Group, Aldrighetti L. , Bartsch F. , Bechstein W. O. , Bednarsch J. , de BenzingBoer C. M. A. , Bouwense S. A. , Capobianco I. , Cescon M. , D’Angelica M. I. , Dewulf M. , de Reuver P. , de Savornin Lohman E. , Efanov M. , Franken L. C. , Geers J. , Giglio M. C. , Gilg S. , Gomez-Gavara C. , van Gulik T. M. , Heil J. , IJzermans J. N. M. , Jansson H. , Kingham T. P. , Lodge P. , Margies R. , Marino R. , Molenaar Q. I. , Nguyen T. A. , Nooijen L. E. , Nota C. L. M. , Poletto E. , Porte R. J. , Prasad R. , Quinn L. M. , Rolinger J. , Ruzzenente A. , Schmelzle M. , Serenari M. , Sultana A. , van Laarhoven S. , Zonderhuis B. M.
Published: March 2024

Background

A right- or left-sided liver resection can be considered in about half of patients with perihilar cholangiocarcinoma (pCCA), depending on tumor location and vascular involvement. This study compared postoperative mortality and long-term survival of right- versus left-sided liver resections for pCCA.

Methods

Patients who underwent major liver resection for pCCA at 25 Western centers were stratified according to the type of hepatectomy—left, extended left, right, and extended right. The primary outcomes were 90-day mortality and overall survival (OS).

Results

Between 2000 and 2022, 1701 patients underwent major liver resection for pCCA. The 90-day mortality was 9% after left-sided and 18% after right-sided liver resection (p < 0.001). The 90-day mortality rates were 8% (44/540) after left, 11% (29/276) after extended left, 17% (51/309) after right, and 19% (108/576) after extended right hepatectomy (p < 0.001). Median OS was 30 months (95% confidence interval [CI] 27–34) after left and 23 months (95% CI 20–25) after right liver resection (p < 0.001), and 33 months (95% CI 28–38), 27 months (95% CI 23–32), 25 months (95% CI 21–30), and 21 months (95% CI 18–24) after left, extended left, right, and extended right hepatectomy, respectively (p < 0.001). A left-sided resection was an independent favorable prognostic factor for both 90-day mortality and OS compared with right-sided resection, with similar results after excluding 90-day fatalities.

Conclusions

A left or extended left hepatectomy is associated with a lower 90-day mortality and superior OS compared with an (extended) right hepatectomy for pCCA. When both a left and right liver resection are feasible, a left-sided liver resection is preferred.
BRICS in the Internet Governance System
Authors: Ignatov Aleksandr
Published: March 2024

The monograph examines the structure of the Internet management system at the present stage, identifies its main internal contradictions and reform scenarios. One of the contradictions is the lack of real levers of influence among the BRICS member countries, which are leaders in digital development, on decisions made in the field of Internet governance. Over the years of cooperation, BRICS has made many decisions on the development of digital infrastructure, and the development of cooperation in the field of information security is promising. The author suggests ways to resolve the existing contradictions, in particular, reforming the institutional structure of ISOC and ICANN, as well as involving developing countries in developing solutions in the field of Internet governance on the BRICS platform. The participation of developing countries will ensure the legitimacy of decisions taken within the framework of the BRICS in this area.
For students, teachers and anyone interested in Internet governance issues.
Czy rodzina doby późnofeudalnej jest nadal atrakcyjnym polem badawczym?
Authors: Kuklo Cezary
Published: March 2024

Artykuł przedstawia perspektywy badawcze związane z intensyfikacją studiów nad strukturami rodzinnymi i wspólnotami domowymi na ziemiach polskich do schyłku feudalizmu. Autor wskazuje na potrzebę poszerzenia i unowocześnienia kwestionariusza pytań badawczych, które powinny doprowadzić do odkrycia wielu interesujących sfer codziennej egzystencji podstawowej komórki zjawisk społecznych i demograficznych. Dalszym pogłębionym badaniom powinno sprzyjać nie tylko poszerzenie katalogu źródeł ujmowanych łącznie, ale w jeszcze większym stopniu wykorzystanie modeli teoretycznych i narzędzi statystycznych (mikrosymulacje).
The Power of Knowing a Woman Is in Charge: Lessons from a Randomized Experiment
Authors: Dobrescu Loretti , Motta Alberto , Shanker Akshay
Published: March 2024

As part of a term-long anonymous assessment, thousands of undergraduate university students were divided into groups, each led by a randomly selected peer. The leader’s gender had no effect on the assessment’s outcomes, but female students led by a female peer achieved 0.26 standard deviations (SD) higher course grades when the gender of the leader was revealed. They also outperformed by 0.22 SD their counterparts in groups in which the leader’s gender was revealed to be male. The mechanism involved attempting more difficult practice questions. Our structural estimates suggest this operated via a stereotype threat reversal that reduced anxiety.

This paper was accepted by Yan Chen, behavioral economics and decision analysis.

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2023.00325 .
Designing Service Menus for Bipartite Queueing Systems
Authors: Caldentey René , Hillas Lisa Aoki , Gupta Varun
Published: March 2024

Designing Fair and Incentive-Compatible Matching Systems

Many service systems face the challenge of dynamically matching customers who have heterogeneous preferences with an available pool of service providers in a fair and equitable manner. The first come, first served (FCFS) service discipline offers a straightforward and fair approach to allocate arriving customers to available servers and manage congestion. However, FCFS may limit the ability of service providers to reach an efficient allocation based on the individual preferences of customers and the characteristics of servers. In “Designing Service Menus for Bipartite Queuing Systems,” Caldentey, Hillas, and Gupta develop a queueing framework to address this dynamic matching problem. Their proposed methodology enables service providers to offer a menu of different service classes, each served by a distinct pool of servers. By thoughtfully designing this menu, a service provider can encourage self-interested customers to select service classes in a way that optimizes the trade-off between quality of matching and waiting time delays.
Finding Creativity in Predictability: Seizing Kairos in Chronos Through Temporal Work in Complex Innovation Processes
Authors: Otto Birke D. , Schuessler Elke S. , Sydow Jörg , Vogelgsang Lukas
Published: March 2024

Managing temporal complexity is a fundamental challenge in complex innovation processes, yet the temporal work whereby actors seize opportune moments (kairos) in an environment dominated by clock-time structures (chronos) remains elusive. Temporal tensions can partly be resolved through entrainment, that is, by aligning activities with dominant temporal structures. However, although entrainment ensures the exploitation of a predefined path, it is unable to harness unexpected developments as opportunities for exploration. Thus, navigating the competing temporal demands of chronos and kairos requires not just ambidextrous but also ambitemporal organizing. Collecting and analyzing in-depth interview and observational data from pharmaceutical drug discovery and development, we find that actors sometimes resolve temporal tensions through entrainment to ensure coordination and predictability. In other instances, however, actors abductively transform temporal tensions into novel interpretations and new courses of action. As such, temporal tensions become more than a bothersome deviation from the planned schedule, but an opportunity for creative agency. This understanding of kairos—as a process unfolding through temporal work—relies not only on detraining from chronos (i.e., momentarily detaching from the dominant temporal structure to question underlying assumptions), but also on its reframing and reconfiguration. We contribute to the literature on complex innovation and temporality by theorizing a transformative perspective on ambitemporal organizing, which relies less on paradoxical notions and instead emphasizes how kairos is enacted and seized within and from chronos.

Funding: This work was supported by German Research Foundation (DFG) funding for the Research Unit “Organized Creativity” [Grant FOR 2161] as well as by the Austrian Science Fund (FWF) [10.55776/I4884].
Prescribing in patients with diabetes
Authors: Robertson Deborah
Published: March 2024

Deborah Robertson provides an overview of recently published articles that may be of interest to non-medical prescribers. Should you wish to look at any of the papers in more detail, a full reference is provided
Evaluation of factors influencing antibiotic prescribing behaviour by independent nurse prescribers
Authors: Green Alyson
Published: March 2024

Antibiotic resistance is an urgent, accelerating global health threat due to inadequate infection prevention and control practices, and sub-optimal prescribing of antibiotics. Health professionals are required to practise antimicrobial stewardship to reduce incidence of antibiotic resistance, and this includes optimal prescribing behaviours. This study aimed to establish factors influencing medical prescribers' and independent nurse prescribers' antibiotic prescribing decisions, and compare the responses between practice settings. Independent nurse prescribers were invited to complete an online questionnaire with 17 antibiotic prescribing statements. Respondents rated their responses on a five-point Likert-type scale ranging from totally disagree to totally agree. A total of 115 questionnaires were completed and analysed. The results showed independent nurse prescribers' antibiotic prescribing decisions may be influenced by patient expectations, diagnostic uncertainty, challenges related to patient follow-up, time pressures and remote consultations. Unlike medical prescribers, they do not report pressure to prescribe antibiotics to maintain a good relationship with the patient. Antibiotic prescribing decisions are influenced by a wide range of factors outside of clinical indication and further research is required to explore these in detail. Independent nurse prescribers require education and training tailored to their specific needs and practice settings.
Advancing inhaled therapy for chronic obstructive pulmonary disease: integrating clinical, economic and environmental considerations
Authors: Bostock Beverley
Published: March 2024

Chronic obstructive pulmonary disease (COPD) has a significant impact on patients and the wider health systems. COPD should be managed holistically, and pharmacological treatment with inhaled bronchodilators (singly, in combination or with inhaled corticosteroids) should be matched to patient need. Choice of inhaler type and specific device should be based on patient need and preference, as well as economic and environmental concerns.
A–Z of prescribing for children
Authors: Davies Kate
Published: March 2024

This series focuses on aspects of prescribing for neonates, children and young people, from A–Z. Aspects of pharmacokinetics will be considered, alongside legal considerations, consent and medications in schools
TIRZEPATIDE
Authors: Rees Sharon
Published: March 2024

In this column, Sharon Rees aims to refresh knowledge and interest in some of the commonly used drugs in a series of posts on X. This month she is talking about #tirzepatide
Direct Enforcement
Authors: Guerson Leonardo
Published: March 2024

Intercomp explores the benefits of a highly accurate and reliable high-speed weigh-in-motion system developed with Poland’s APM Pro, featuring the Strain Gauge Strip Sensors
Joint Forces
Authors: Schmidt Stefanie
Published: March 2024

An interview with Christian U Haas, CEO of PTV Group and Econolite, reveals how collaborative technology can play a crucial role in simplifying the complexity of mobility