bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbohydrate antigen 125: a useful marker of congestion, fibrosis, and prognosis in heart failure with preserved ejection fraction
Authors: Menghoum Nassiba , Badii Maria Chiara , Deltombe Matthieu , Lejeune Sibille , Roy Clotilde , Vancraeynest David , Pasquet Agnes , Gerber Bernhard L. , Horman Sandrine , Gruson Damien , Beauloye Christophe , Pouleur Anne‐Catherine
Published: February 2024

Aims

Heart failure (HF) with preserved ejection fraction (HFpEF) is a disease associated with high morbidity and mortality, for which it is difficult to identify patients with the poorest prognosis in routine clinical practice. Carbohydrate antigen 125 (CA 125) has been shown to be a potential marker of congestion and prognosis in HF. We sought to better characterize HFpEF patients with high CA 125 levels by using a multimodal approach.

Methods and results

We prospectively enrolled 139 HFpEF patients (78 ± 8 years; 60% females) and 25 controls matched for age and sex (77 ± 5 years; 60% females). They underwent two‐dimensional echocardiography, cardiac magnetic resonance with late gadolinium enhancement [including extracellular volume (ECV) measurement], and serum measurements of CA 125 level. The primary endpoint of the study was a composite of all‐cause mortality or first HF hospitalization. The prognostic impact of CA 125 was determined using Cox proportional hazard models. Median CA 125 levels were significantly higher in HFpEF patients compared with controls [CA 125: 23.5 (14.5–44.7) vs. 14.6 (10.3–21.0) U/mL, P = 0.004]. CA 125 levels were positively correlated with a congestion marker [N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels, Pearson's r = 0.37, P < 0.001] and markers of cardiac fibrosis estimated by both ECV (Pearson's r = 0.26, P = 0.003) and fibroblast growth factor 23 levels (Pearson's r = 0.50, P < 0.001). Over a median follow‐up of 49 (22–64) months, 97 HFpEF patients reached the composite endpoint. Even after adjustment for the Meta‐Analysis Global Group in Chronic risk score, a CA 125 level ≥35 U/mL was still a significant predictor of the composite endpoint [hazard ratio (HR): 1.58 (1.04–2.41), P = 0.032] and more particularly of HF hospitalization [HR: 1.81 (1.13–2.92), P = 0.014]. In contrast, NT‐proBNP levels were not an independent predictor.

Conclusions

CA 125 levels were significantly higher in HFpEF patients compared with controls matched for age and sex and were associated with markers of congestion and cardiac fibrosis. CA 125 levels were a strong and independent predictor of HF hospitalization in HFpEF patients. These data suggest a potential value of CA 125 as a biomarker for staging and risk prediction in HFpEF.
Notch signaling in adipose tissue macrophages prevents diet‐induced inflammation and metabolic dysregulation
Authors: Siouti Eleni , Salagianni Maria , Manioudaki Maria , Pavlos Eleftherios , Klinakis Apostolos , Galani Ioanna‐Evdokia , Andreakos Evangelos
Published: February 2024

The importance of macrophages in adipose tissue (AT) homeostasis and inflammation is well established. However, the potential cues that regulate their function remain incompletely understood. To bridge this important gap, we sought to characterize novel pathways involved using a mouse model of diet‐induced obesity. By performing transcriptomics analysis of AT macrophages (ATMs), we found that late‐stage ATMs from high‐fat diet mice presented with perturbed Notch signaling accompanied by robust proinflammatory and metabolic changes. To explore the hypothesis that the deregulated Notch pathway contributes to the development of AT inflammation and diet‐induced obesity, we employed a genetic approach to abrogate myeloid Notch1 and Notch2 receptors. Our results revealed that the combined loss of Notch1 and Notch2 worsened obesity‐related metabolic dysregulation. Body and AT weight gain was higher, blood glucose levels increased and metabolic parameters were substantially worsened in deficient mice fed high‐fat diet. Moreover, serum insulin and leptin were elevated as were triglycerides. Molecular analysis of ATMs showed that deletion of Notch receptors escalated inflammation through the induction of an M1‐like pro‐inflammatory phenotype. Our findings thus support a protective role of myeloid Notch signaling in adipose tissue inflammation and metabolic dysregulation.
Investigation of seismic fragility curves of unbonded FREIs: Adaptive characteristics and modeling sensitivity
Authors: Sheikh Hediyeh , Ruparathna Rajeev , Van Engelen Niel C.
Published: February 2024

Fiber‐reinforced elastomeric isolators (FREIs) are composed of layers of elastomer reinforced with either steel or fibers, and can be placed in a bonded or unbonded configuration between the upper and lower supports. The use of fiber reinforcement in FREIs was intended to reduce the production and installation costs compared to common steel‐reinforced elastomeric isolators (SREIs) and to develop an isolator suitable for widespread application, particularly in developing countries. The unique rollover deformation exhibited by unbonded FREIs (UFREIs), due to their flexible fiber reinforcement, enables them to adapt to multiple performance objectives at different hazard levels. In this study, the impact of different numerical models of UFREIs on the seismic response and failure probability of structures is investigated. The research employs incremental dynamic analysis and the development of fragility curves for different limit states, considering three sets of ground motions (including far‐field and pulse‐like). Moreover, the effect of full rollover was investigated by comparing the fragility curves of UFREIs when supported on modified support geometries, which involved three types of support: unmodified, accelerated, and delayed full rollover. The effectiveness of the adaptive characteristics to behave as a displacement restrain is demonstrated. The results emphasize the importance of employing an accurate model to simulate the behavior of UFREIs as an adaptive device for effectively utilizing their potential capacity, particularly at larger displacements where there is more dissipated energy due to full rollover.
Near complete remission of an inoperable pancreatic acinar cell carcinoma after BRAF‐/MEK‐inhibitor treatment—A case report and review of the literature
Authors: von Fritsch Lennart , von Bubnoff Nikolas , Weber Klaus , Kirfel Jutta , Schreiber Cleopatra , Keck Tobias , Wellner Ulrich
Published: February 2024

Introduction

Pancreatic acinar cell carcinomas are rare malignant neoplasms. High‐quality evidence about the best treatment strategy is lacking. We present the case of a 52‐year‐old male with a BRAFV600E‐mutated PACC who experienced a complete remission after chemotherapy with BRAF‐/MEK‐inhibitors.

Case

The patient presented with upper abdomen pain, night sweat, and weight loss. CT scan showed a pancreatic tumor extending from the pancreas head to body. Histological workup identified an acinar cell carcinoma. As the tumor was inoperable, chemotherapy with FOFIRNIOX was initiated and initially showed a slight regression of disease. The regimen had to be discontinued due to severe side effects. Molecular analysis identified a BRAFV600E mutation, so the patient was started on BRAF‐ and MEK‐inhibitors (dabrafenib/trametinib). After 16 months, CT scans showed a near complete remission with a markedly improved overall health.

Discussion

Studies suggest that up to one‐fourth of PACCs carry a BRAF mutation and might therefore be susceptible to a BRAF‐/MEK‐inhibitor therapy. This offers a new therapeutic pathway to treat this rare but malignant neoplasm.
Phase‐encodedfMRItracks down brainstorms of natural language processing with subsecond precision
Authors: Lei Victoria Lai Cheng , Leong Teng Ieng , Leong Cheok Teng , Liu Lili , Choi Chi Un , Sereno Martin I. , Li Defeng , Huang Ruey‐Song
Published: February 2024

Natural language processing unfolds information overtime as spatially separated, multimodal, and interconnected neural processes. Existing noninvasive subtraction‐based neuroimaging techniques cannot simultaneously achieve the spatial and temporal resolutions required to visualize ongoing information flows across the whole brain. Here we have developed rapid phase‐encoded designs to fully exploit the temporal information latent in functional magnetic resonance imaging data, as well as overcoming scanner noise and head‐motion challenges during overt language tasks. We captured real‐time information flows as coherent hemodynamic waves traveling over the cortical surface during listening, reading aloud, reciting, and oral cross‐language interpreting tasks. We were able to observe the timing, location, direction, and surge of traveling waves in all language tasks, which were visualized as “brainstorms” on brain “weather” maps. The paths of hemodynamic traveling waves provide direct evidence for dual‐stream models of the visual and auditory systems as well as logistics models for crossmodal and cross‐language processing. Specifically, we have tracked down the step‐by‐step processing of written or spoken sentences first being received and processed by the visual or auditory streams, carried across language and domain‐general cognitive regions, and finally delivered as overt speeches monitored through the auditory cortex, which gives a complete picture of information flows across the brain during natural language functioning.

Practitioner Points

Phase‐encoded fMRI enables simultaneous imaging of high spatial and temporal resolution, capturing continuous spatiotemporal dynamics of the entire brain during real‐time overt natural language tasks.

Spatiotemporal traveling wave patterns provide direct evidence for constructing comprehensive and explicit models of human information processing.

This study unlocks the potential of applying rapid phase‐encoded fMRI to indirectly track the underlying neural information flows of sequential sensory, motor, and high‐order cognitive processes.
The use of antipsychotics in obsessive compulsive disorder
Authors: Conti Dario , Girone Nicolaja , Boscacci Maria , Casati Lorenzo , Cassina Niccolò , Cerolini Lucia , Giacovelli Luca , Viganò Caterina , Conde Marian Mora , Cremaschi Laura , Dell’Osso Bernardo M.
Published: February 2024

Obsessive‐compulsive disorder (OCD) is a chronic disease with a prevalence in the general population of around 2%–3%, generally accompanied by a severe impairment of functioning and quality of life. A consistent subgroup of patients may not achieve adequate symptom remission with first‐line treatments (i.e., cognitive behavioral therapy, selective serotonin reuptake inhibitors [SSRIs]). The most validated option for treatment‐resistant cases relies on the augmentative use of antipsychotics to SSRIs, preferably of the ‘second generation’. Indeed, dopamine appears to be crucially involved in OCD neuropathology due to its implication in systems relating to goal‐directed behaviour and maladaptive habits. Nevertheless, the mechanism of action of antipsychotics in OCD symptom improvement is still unclear. Risperidone, aripiprazole, and haloperidol seem to be the most useful medications, whereas ‘first generation’ antipsychotics may be indicated in case of comorbidity with tics and/or Tourette Syndrome. Antipsychotic augmentation may be also related to side‐effects, particularly in the long term (e.g., alteration in metabolic profile, sedation, extrapyramidal symptoms). The present mini‐review sought to provide the most updated evidence on augmentative antipsychotic use in treatment‐resistant patients with OCD, providing a road map for clinicians in daily practice and shedding light on avenues for further research.
Long‐term exposure to air pollution and incidence of gastric and the upper aerodigestive tract cancers in a pooled European cohort: The ELAPSE project
Authors: Nagel Gabriele , Chen Jie , Jaensch Andrea , Skodda Lea , Rodopoulou Sophia , Strak Maciej , de Hoogh Kees , Andersen Zorana J. , Bellander Tom , Brandt Jørgen , Fecht Daniela , Forastiere Francesco , Gulliver John , Hertel Ole , Hoffmann Barbara , Hvidtfeldt Ulla Arthur , Katsouyanni Klea , Ketzel Matthias , Leander Karin , Magnusson Patrik K. E. , Pershagen Göran , Rizzuto Debora , Samoli Evangelia , Severi Gianluca , Stafoggia Massimo , Tjønneland Anne , Vermeulen Roel C. H. , Wolf Kathrin , Zitt Emanuel , Brunekreef Bert , Hoek Gerard , Raaschou‐Nielsen Ole , Weinmayr Gudrun
Published: February 2024

Air pollution has been shown to significantly impact human health including cancer. Gastric and upper aerodigestive tract (UADT) cancers are common and increased risk has been associated with smoking and occupational exposures. However, the association with air pollution remains unclear. We pooled European subcohorts (N = 287,576 participants for gastric and N = 297,406 for UADT analyses) and investigated the association between residential exposure to fine particles (PM2.5), nitrogen dioxide (NO2), black carbon (BC) and ozone in the warm season (O3w) with gastric and UADT cancer. We applied Cox proportional hazards models adjusting for potential confounders at the individual and area‐level. During 5,305,133 and 5,434,843 person‐years, 872 gastric and 1139 UADT incident cancer cases were observed, respectively. For gastric cancer, we found no association with PM2.5, NO2 and BC while for UADT the hazard ratios (95% confidence interval) were 1.15 (95% CI: 1.00–1.33) per 5 μg/m3 increase in PM2.5, 1.19 (1.08–1.30) per 10 μg/m3 increase in NO2, 1.14 (1.04–1.26) per 0.5 × 10−5 m−1 increase in BC and 0.81 (0.72–0.92) per 10 μg/m3 increase in O3w. We found no association between long‐term ambient air pollution exposure and incidence of gastric cancer, while for long‐term exposure to PM2.5, NO2 and BC increased incidence of UADT cancer was observed.
Occupational asbestos exposure and risk of esophageal cancer: A systematic review and meta‐analysis
Authors: Seyyedsalehi Monireh Sadat , Boffetta Paolo
Published: February 2024

Esophageal cancer (EC), which includes squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), is an important cancer with poor prognosis and high mortality rate. Several occupational exposures have been associated with EC. We aim to investigate the association between occupational asbestos exposure and EC risk, considering types of asbestos and histology of the disease. We included studies mentioned in the list of references in previous reviews and pooled analyses, and we conducted an independent search in PubMed and Scopus. Forest plots of relative risks (RR) were constructed based on the association between occupational asbestos and EC risk. Random‐effects models were used to address heterogeneity between 48 independent cohort and case‐control studies. We found an association between occupational asbestos exposure and EC (meta‐relative risk [RR] = 1.20, 95% confidence interval [CI] = 1.09‐1.32; I2 = 58.8%, p‐heterogeneity [het] <.001). The results of stratification by job (p‐het = .20) indicate an increased RR among asbestos product workers (RR = 1.39, 95% CI = 1.07‐1.81), asbestos applicators (RR = 1.41, 95% CI = 1.20‐1.67), and construction workers (RR = 1.12, 95% CI = 1.02‐1.24). There was no heterogeneity in meta‐RR according to outcome (p = .29), geographic region (p = .69), year of publication (p = .59), quality score (p = .73), asbestos type (p = .93), study design (p = .87), and gender (p = .88), control for potential confounders (p = .20), year of first employment (p = .94) and exposure level (p = .43). The stratification analysis by histology type found an increased RR for both ESCC 1.33(1.03‐1.71) and EAC 1.45(1.03‐2.04) (p‐het = .68). We didn't find evidence of publication bias (p = .07). The results of our study suggest that occupational asbestos exposure is associated with an increased risk of EC in both histology types.
Environmental drivers of the rising incidence of early‐onset colorectal cancer in the United States
Authors: Chen Jianjiu , Terry Mary Beth , Dalerba Piero , Hur Chin , Hu Jianhua , Yang Wan
Published: February 2024

Incidence of early‐onset (diagnosed before age 50) colorectal cancer (EOCRC) has increased alarmingly since the 1990s in the United States. This study investigated what environmental exposures may have driven this increase. We obtained EOCRC incidence data from the Surveillance, Epidemiology, and End Results Program, and data for 11 exposures, for example, body mass index (BMI), from long‐term national surveys. We aggregated these data for 30 to 49‐year‐olds during 1992 to 2016 by population subgroups defined by calendar period, age, race and sex, and used negative binomial regression models to identify and estimate associations of EOCRC with multiple exposures. Furthermore, we used counterfactual modeling to quantify contributions of identified risk factors to EOCRC incidence. The top models (with lowest Bayesian Information Criteria) consistently identified excess body weight, represented by overweight and obesity (BMI ≥25) or obesity alone (BMI ≥30), as the strongest risk factor. The best‐performing model estimated increased EOCRC incidence due to overweight and obesity, with an incidence rate ratio (95% confidence interval) of 1.20 (1.17‐1.22) for white men, 1.04 (1.00‐1.08) for black men, 1.17 (1.15‐1.21) for white women and 1.03 (0.97‐1.08) for black women. Increases in overweight and obesity prevalence contributed to an estimated 30% (standard error: 1%) for men and 28% (standard error: 2%) for women of ECORC incidence during 1992 to 2016. These findings suggest excess body weight substantially contributed to and is likely a primary driver of the rising incidence of EOCRC in the United States. Prevention of excess weight gain may help lower colorectal cancer risk early in life.
Association between gestational weight gain and behavioral problems of the offspring aged 6–7 years: A population‐based study in Japan
Authors: Terada Shuhei , Isumi Aya , Doi Satomi , Tani Yukako , Fujiwara Takeo
Published: February 2024

Objective

To identify the optimal gestational weight gain (GWG) thresholds for behavioral problems and prosocial behavior in 6‐ to 7‐year‐old children.

Methods

A retrospective cohort study was conducted using data from the Adachi Child Health Impact of Living Difficulty study, including all first‐graders in public schools in Adachi, Tokyo, in 2017, 2019, and 2021 (n = 11 048, response rate = 80.1%). GWG was based on clinical records in the Mother and Child Health Handbook. Total difficulties and prosocial behavior were assessed using the Strength and Difficulties Questionnaire. Logistic regression models with restricted cubic splines, and quintile categories were employed to examine the association of GWG with the clinical range of total difficulties and prosocial behavior, controlling for covariates.

Results

The association between GWG and total difficulties exhibited a reverse J‐shaped pattern, with low GWG, but not high GWG, increasing the risk (odds ratio [OR] 1.20, 95% confidence interval [CI] 1.01–1.42, P = 0.039 for GWG < 7 kg; OR 1.03, 95% CI 0.85–1.24, P = 0.786 for GWG > 14 kg), referencing the median (10 kg). High GWG was associated with a lower risk of problems in prosocial behavior (OR = 0.77, 95% CI 0.62–0.95, P = 0.017 for GWG > 14 kg; OR 1.06, 95% CI 0.88–1.27, P = 0.532 for GWG <7 kg).

Conclusion

GWG less than 7 kg may increase the risk of total difficulties, whereas GWG over 14 kg may serve as a protective factor for prosocial behavior in 6‐ to 7‐year‐old children.
Three cases of sperm immobility for intracytoplasmic sperm injection using testicular sperm
Authors: Mimura Noboru , Takeshima Teppei , Aoki Shun , Saito Tomoki , Karibe Jurii , Yumura Yasushi
Published: February 2024

Introduction

Sperm immobility is a condition in which sperm are viable but not motile. We reported three patients with sperm immobility, who underwent testicular sperm extraction‐intracytoplasmic sperm injection.

Case presentation

In case 1, a 32‐year‐old patient with sperm immobility had previously undergone intracytoplasmic sperm injection with ejaculated sperm; however, pregnancy was unsuccessful. testicular sperm extraction‐intracytoplasmic sperm injection was performed at our clinic, and pregnancy was achieved. In case 2, a 23‐year‐old patient with clinical varicocele whose semen analysis revealed sperm immobility underwent varicocelectomy, without improvement. Using the hypo‐osmotic swelling test technique, testicular sperm extraction‐intracytoplasmic sperm injection was performed; however, pregnancy was not achieved. In case 3, a 44‐year‐old patient with sperm immobility underwent testicular sperm extraction, and motile sperm were retrieved. testicular sperm extraction‐intracytoplasmic sperm injection using these sperm resulted in pregnancy.

Conclusion

Although testicular sperm extraction‐intracytoplasmic sperm injection is not considered a solution in patients with sperm immobility, pregnancies were achieved. testicular sperm extraction‐intracytoplasmic sperm injection may be successful in some cases in which ejaculated sperm intracytoplasmic sperm injection is unsuitable.
A target region extraction method for ultrasound medical images based on improvedPRIDNetandUCTransNet
Authors: Zhai Jintao , Tian Feng , Li Ang , Qian Shengyou , Wang Runmin , Zou Xiao
Published: February 2024

Computer‐aided diagnosis is pivotal in augmenting the diagnostic efficiency of ultrasound images. Nonetheless, the substantial presence of noise and artifacts in ultrasound images presents a challenge to the precise segmentation of the target region. To highlight and analyze the diagnostic information such as tissues, organs, and lesions in ultrasound medical images more accurately, a target region extraction method combining the improved PRIDNet and UCTransNet for ultrasound medical images is proposed. The method sequentially enhances and segments the target region of the image, thereby solving the problem of inconspicuous target region caused by noise and artifacts in ultrasound images. There are three key characteristics: (i) The feature extraction part of the enhancement network (improved PRIDNet) is redesigned for speckle noise to improve the network's ability to extract information and highlight the feature information of the target region in ultrasound images. (ii) The segmentation network with the addition of the underlying information on UCTransNet would effectively improves Channel‐wise Cross fusion Transformer (CCT) and decoder feature fusion capability. (iii) By combining the enhancement network with the segmentation network, we can further improve the segmentation accuracy of the target region in the presence of noise interference. The experiments conducted on both UFSU that we prepared and on some public datasets including BUSI, FHC, and CT2US have demonstrated that The proposed method attains MIoU, DSC, Acc, and HD of 96.34%, 98.12%, 99.35%, and 8.64 in CT2US, respectively. The method significantly surpasses those certain state‐of‐the‐art methods, demonstrating its potential to offer valuable guidance for clinical treatment. The code will be publicly released athttps://github.com/425877/Target-Region-Extraction-Method-for-Ultrasound-Medical-Images.
Changes in guilt cognitions mediate the effect of trauma‐informed guilt reduction therapy on PTSD and depression outcomes
Authors: Kline Alexander C. , Harlé Katia M. , Panza Kaitlyn E. , Nichter Brandon , Lyons Robert , Pitts Michelle , Haller Moira , Allard Carolyn B. , Capone Christy , Norman Sonya B.
Published: February 2024

Objective

Trauma‐informed guilt reduction therapy (TrIGR), a six‐session cognitive behavioral therapy targeting trauma‐related guilt and distress, reduces guilt and symptoms of posttraumatic stress disorder (PTSD) and depression, yet little is known regarding how and why TrIGR may be effective.

Method

This study examined treatment‐related changes in avoidant coping and trauma‐related guilt cognitions as possible mediators of treatment effects on PTSD and depression outcomes at 3‐ and 6‐month follow‐up. Data were from a randomized controlled trial for treatment of trauma‐related guilt comparing TrIGR and supportive care therapy among 145 post‐9/11 US veterans (Mage = 39.2 [8.1], 93.8% male).

Results

At pretreatment, most (86%) met PTSD criteria. Intent to treat analyses using parallel mediation models indicated changes in guilt cognitions, but not avoidant coping, mediated the effect of TrIGR on reducing PTSD severity at 3‐month (a × b = −0.15, p < 0.01, 95% CI: [−0.24 to −0.06], p = 0.001) and 6‐month (a × b = −0.17, 95% CI: [−0.26 to −0.07], p = 0.001) follow‐up. Similarly, changes in guilt cognitions, but not avoidant coping, mediated the effect of TrIGR on reducing depression severity at 3‐month (a × b = −0.10, 95% CI: [−0.18 to −0.02], p = 0.02) and 6‐month (a × b = −0.11, 95% CI: [−0.20 to −0.03], p = 0.01) follow‐up.

Conclusions

Compared to guilt cognitions, changes in avoidant coping were less integral to downstream PTSD and depression symptom reduction. Guilt cognition change may be a salient active ingredient of PTSD and depression treatment for those with trauma‐related guilt and a key therapy element to which providers should be attuned.
Exposure‐Response Relationships for Pralsetinib in Patients with RET‐Altered Thyroid Cancer or RET Fusion‐Positive Nonsmall Cell Lung Cancer
Authors: Kassir Nastya , McDougall David , Kuruvilla Denison , Kim Sean , Kumar Shaun , Rahman Ahmadur , Ruf Thorsten , Cheeti Sravanthi , Ankrom Wendy
Published: February 2024

Pralsetinib is a highly potent oral kinase inhibitor of oncogenic RET (rearranged during transfection) fusions and mutations. Pralsetinib received approval from the United States Food and Drug Administration for the treatment of patients with metastatic RET fusion‐positive non‐small cell lung cancer (NSCLC), and received accelerated approval for the treatment of patients with RET fusion‐positive thyroid cancer. Exposure–response (ER) analyses of efficacy were performed separately in patients with thyroid cancer and in patients with NSCLC, but data for all patients were pooled for the safety analysis. ER models were developed with time‐varying exposure; the effect of covariates was also examined. For patients with NSCLC, a higher starting dose was associated with improved progression‐free survival (PFS), but this improvement did not correlate with a higher exposure overall. Significant covariates included sex and baseline Eastern Cooperative Oncology Group (ECOG) score. For patients with thyroid cancer, a higher exposure was associated with improved PFS. Significant covariates included prior systemic cancer therapy and ECOG score. For safety, higher exposure was associated with a greater risk of grade ≥3 anemia, pneumonia, and lymphopenia. Patients with an ECOG score of ≥1 had an increased risk of grade ≥3 pneumonia. Non‐White patients had a lower risk of grade ≥3 lymphopenia. ER analysis revealed that higher pralsetinib exposure was associated with improved PFS in thyroid cancer, but not in NSCLC. However, a higher starting dose (ie, 400 vs ≤300 mg daily) was correlated with better PFS for all indications. Higher exposure was also associated with an increased risk of grade ≥3 adverse events (AEs); however, the overall incidence of these events was acceptably low (≤20%). This analysis supports the use of a 400 mg starting dose of pralsetinib, allowing for dose reduction in the event of AEs.
Family‐based preventive intervention for children of parents with severe mental illness: A randomized clinical trial
Authors: Müller Anne Dorothee , Gjøde Ida Christine Tholstrup , Thams Nikolaj , Ingversen Sidsel , Moszkowicz Mala , Jepsen Jens Richardt Møllegaard , Mikkelsen Lisbeth Juhl , Nielsen Signe Sofie , Hemager Nicoline , Nordentoft Merete , Thorup Anne A. E.
Published: February 2024

Background

Children of parents with a severe mental illness have an increased risk of developing a lifetime mental illness. We aimed to compare the effects of a preventive family‐based intervention, VIA Family, with treatment as usual (TAU) on these children's global functioning.

Methods

Between 2017 and 2021, we conducted a pragmatic, rater‐blinded, two‐arm parallel‐group superiority trial in Denmark. Families with at least one child aged 6–12 years and at least one biological parent with schizophrenia spectrum disorder, bipolar disorder, or recurrent major or moderate depression were included. We randomly allocated 95 families with their 113 children to VIA Family or TAU (ratio 1:1). VIA Family was individually tailored and based on case management. The intervention included options for psychoeducation, parental support, and treatment for emerging child psychiatric symptoms. Blinded raters assessed children and their families at baseline and after 18 months. The primary outcome was the difference in change between groups at end‐of‐treatment in daily global functioning measured with the Children's Global Assessment Scale. Secondary outcomes were emotional and behavioral problems and days absent from school. We analyzed data blinded to allocation.

Results

At post‐intervention, differences in mean change from baseline between VIA Family and TAU were non‐significant (CGAS: −1.20, 95% CI = −6.61; 4.21, p = 0.66), as were the differences on the secondary and exploratory outcomes.

Conclusion

Contrary to our hypothesis, we did not find a superior effect of VIA Family compared with TAU. The short follow‐up period and large sample heterogeneity might explain the null findings. Therefore, a possible long‐term, preventive treatment effect has yet to be explored.
The importance of consensus science to managing phosphorus in the environment: SERA‐17 and the legacy of Andrew Sharpley
Authors: Macrae Merrin L. , Kleinman Peter J. A. , Osmond Deanna , Shober Amy , Nelson Nathan
Published: February 2024

Phosphorus (P) loss from agricultural systems to surface waters, and ultimately, eutrophication, presents a wicked problem requiring transdisciplinary solutions. The mission of SERA‐17 (Southern Extension and Research Advisory Information Exchange Group‐17) has been to address this problem by developing “Innovative Solutions to Minimize Phosphorus Losses from Agriculture.” Over the course of his career, Dr. Andrew Sharpley demonstrated a rare ability to collaboratively achieve consensus around issues related to the science and management of P. The SERA‐17 organization served as the central community of experts and stakeholders where that consensus was built and applied. The consensus‐based approach, demonstrated by Sharpley and at the core of the SERA‐17 organization, was routinely applied to key areas of P science to produce applied outcomes that have been readily adopted: advance foundational science to resolve knowledge gaps and to promote innovation; promote consistency in methods to facilitate comprehensive investigations and conclusions across a diversity of systems; engage diverse stakeholders to prioritize research, and ultimately, ensure that outcomes reflect a plurality of perspectives; and deliver pragmatic solutions that reflect the best information available at a particular time. We review the history of SERA‐17 in delivering new science and management recommendations for P, with an eye to elucidating Sharpley's role and legacy in this process.
Relationship between the atrial‐activation pattern around the triangle of Koch and successful ablation sites in slow‐fast atrioventricular nodal reentrant tachycardia
Authors: Watanabe Tomonori , Hachiya Hitoshi , Watanabe Hiroaki , Anno Kazunori , Okuyama Takafumi , Harunari Tomohiko , Yokota Ayako , Kamioka Masashi , Komori Takahiro , Torigoe‐Kurosu Yuko , Makimoto Hisaki , Kabutoya Tomoyuki , Kimura Yoshifumi , Imai Yasushi , Kario Kazuomi
Published: February 2024

Background

The precise details of atrial activation around the triangle of Koch (ToK) remain unknown. We evaluated the relationship between the atrial‐activation pattern around the ToK and success sites for slow‐pathway (SP) modification ablation in slow‐fast atrioventricular reentrant tachycardia (AVNRT).

Methods

Thirty patients with slow‐fast AVNRT who underwent successful ablation were enrolled. Atrial activation around the ToK during sinus rhythm was investigated using ultra‐high‐density mapping pre‐ablation. The relationships among features of atrial‐activation pattern and success sites were examined.

Results

Of 30 patients (22 cryoablation; 8 radiofrequency ablation), 26 patients had a collision site of two wavefronts of delayed atrial activation within ToK, indicating a success site. The activation‐search function of Lumipoint software, which highlights only atrial activation with a spatiotemporal consistency, showed non‐highlighted area on the tricuspid‐annulus side of ToK. In 23 of the patients, a spiky potential was recorded at that collision site outside the Lumipoint‐highlighted area. Fifteen cryoablation patients with a success site coincident with a collision site outside the Lumipoint‐highlighted area had significantly more frequent disappearances of SP after initial cryoablation (46.7% vs. 0%, p = .029), fewer cryoablations (3.7 ± 1.8 vs. 5.3 ± 1.3, p = .045), and shorter procedure times (170 ± 57 vs. 228 ± 91 min, p = .082) compared to the seven cryoablation patients without such sites. Four patients had transient AV block by ablation inside the Lumipoint‐highlighted area with fractionated signals, but no patient developed permanent AV block or recurrence post‐procedure (median follow‐up: 375 days).

Conclusions

SP modification ablation at the collision site of atrial activation of the tricuspid‐annulus side along with a spiky potential could provide a better outcome.
Where does stress happen? Ecological momentary assessment of daily stressors using a mobile phone app
Authors: Yao Xing , Nelson Erik J. , Stavrianakis Kostas , Huang Ting‐Yen (Tim) , Moran Casey , Shih Patrick C. , Jordan Evan J.
Published: February 2024

Despite the importance of daily stress to individuals' health and wellbeing, few studies have explored where stress happens in real time, that is, dynamic stress processes in different spaces. As such, stress interventions rarely account for the environment in which stress occurs. We used mobile phone based ecological momentary assessment (EMA) to collect daily stress data. Thirty‐three participants utilized a mobile‐phone‐based EMA app to self‐report stressors as they went about their daily lives. Geographic coordinates were automatically collected with each stress report. Data from thematic analysis of stressors by location (home, work, work from home, other) were used to determine whether certain stressors were more prevalent in certain environments. Nine daily stressors significantly differed by location. Work‐related stress was reported more often at work. Pets, household chores, sleep, and media‐related stressors were reported most at home. Physical illnesses, vehicle issues, and safety/security stressors occurred most often while participants were “working from home.” Traffic‐related stress was experienced more commonly in “other” environments. Other 18 stressors were generated regardless of location, suggesting that these stressors were persistent and without respect to location. Study findings expand the understanding of environments in which specific stressors occur, providing baseline data for potential targeted “just‐in‐time” stress interventions tailored to unique stressors in specific environments. We also provide findings related to the “work from home” phenomenon. Further work is needed to better understand the unique stressors among the large number of individuals who transitioned to working from home during and after the COVID‐19 pandemic.
Summing Sneddon–Bessel series explicitly
Authors: Durán Antonio J. , Pérez Mario , Varona Juan Luis
Published: February 2024

We sum in a closed form the Sneddon–Bessel series

where
is an integer,
with
and
are the zeros of the Bessel function
of order 
. In most cases, the explicit expressions for these sums involve hypergeometric functions
. As an application, we prove some extensions of the Kneser–Sommerfeld expansion. For instance, we show that

if
and
(here,
denotes the Bessel function of the second kind), which becomes the Kneser–Sommerfeld expansion when
.
Reselling or dual selling? The role of consumer‐to‐manufacturer e‐commerce platforms' voluntary investment
Authors: Zhao You , Hou Rui , Chen Ying‐Ju
Published: February 2024

Recent years have witnessed e‐commerce platforms that voluntarily invest in new digital technologies to help their suppliers reduce production costs. To examine its impact on channel structure, we develop a supply chain model consisting of a supplier and an e‐commerce platform who purchases products from the supplier at a wholesale price and sells them to end markets. In addition, the supplier has the option to accept the marketplace by paying a commission fee charged by the platform. We show that the presence of voluntary investment on production improvement can overturn some classical insights from prior studies. For example, a higher marketplace commission fee can lead to a lower selling quantity in the marketplace, but a higher order quantity in the reselling channel under certain conditions. This stands in strict contrast to the opposite finding when the platform invests instead on demand enhancement. In addition, previous studies suggest that offering the supplier the marketplace option is beneficial to the supplier but is detrimental to the platform. However, with voluntary investment, the platform can benefit from allowing the supplier to encroach via the marketplace, and in some situations the supplier suffers from having such an option. We find that the commission fee and the production cost are two interacting forces steering equilibrium decisions for supply chain members, and we characterize the concise operating regimes for the channel structure choices on behalves of the supplier and the platform. A number of extensions are discussed, including product substitution level, investment cost structure, whether the quantity decisions are made simultaneously or sequentially, voluntary investment timing, and endogenous commission fee.
Real‐world data of a digitally enabled, time‐restricted eating weight management program in public sector workers living with overweight and obesity in the United Kingdom: A service evaluation of the Roczen program
Authors: Brown Adrian , Dobbie Laurence J. , Falvey Laura , Patel Dipesh C. , Kwan Jonathan T. C. , Steinmo Siri , Chow Ling , McGowan Barbara M.
Published: February 2024

Introduction

The health of the United Kingdom workforce is key; approximately 186 million days are lost to sickness each year. Obesity and type 2 diabetes (T2D) remain major global health challenges. The aim of this retrospective service evaluation was to assess the impact of a digitally enabled, time‐restricted eating (TRE) intervention (Roczen Program, Reset Health Ltd) on weight and other health‐related outcomes.

Methods

This service evaluation was conducted in people living with overweight/obesity, with 89% referred from public sector employers. Participants were placed on a TRE, low‐carbohydrate, moderate protein plan delivered by clinicians and mentors with regular follow up, dietary guidance, goal setting, feedback, and social support.

Results

A total of 660 members enrolled and retention was 41% at 12 months. The majority were female (73.2%), 58.9% were of White ethnicity, with a mean (SD) age of 47.5 years (10.1), and a body mass index of 35.0 kg/m2 (5.7). Data were available for 82 members at 12‐month. At 12‐month, members mean actual and percentage weight loss was −9.0 kg (7.0; p < 0.001) and −9.2% (6.7, p < 0.001) respectively and waist circumference reduced by −10.3 cm (10.7 p < 0.001), with 45.1% of members achieving ≥10% weight loss. Glycated hemoglobin was significantly improved at 6 months in people living with T2D (−11 mmol/mol [5.7] p = 0.012). Binge eating score significantly reduced (−4.4 [7.0] p = 0.006), despite cognitive restraint increasing (0.37 [0.6] p = 0.006).

Conclusion

Our service evaluation showed that the Roczen program led to clinically meaningful improvements in body weight, health‐related outcomes and eating behaviors that were sustained at 12‐month.
Shifting perspectives and transformative change: Parent perspectives of an active music engagement intervention for themselves and their child with cancer
Authors: Stegenga Kristin , Henley Amanda K. , Harman Elizabeth , Robb Sheri L.
Published: February 2024

Background

Children with cancer (ages 3–8 years) and their parents experience significant, interrelated distress associated with cancer treatment. Active music engagement (AME) uses music‐based play and shared music‐making to mitigate this distress. To advance our understanding about how AME works and its essential features, we interviewed parents who received the AME intervention as part of a multi‐site mechanistic trial. The purpose of this qualitative analysis was to describe parents’ experiences of AME for themselves and their child and to better understand how the intervention worked to lower parent–child distress.

Procedure

We conducted a total of 43 interviews with parents/caregivers, and purposively analyzed all interviews from underrepresented groups based on race/ethnicity and parent role. We used thematic analysis and achieved thematic redundancy after analyzing 28 interviews.

Results

The following statement summarizes resulting themes: Music therapists skillfully use AME to create a safe and healthy space (Theme 1), where parents/children have transformative experiences (Theme 2) that lead to learning and enactment (Theme 3) of new skills that counteract suffering (Theme 4) through empowerment, connectedness, and sustained relief.

Conclusions

This work elucidates how AME works to counteract stressful qualities of cancer treatment. As parents witnessed positive and transformative changes in their child, they experienced relief and reported shifts in their perspective about cancer treatment. This led to learning and use of music as a coping strategy that extended beyond therapist‐led sessions. Accessible, music‐based interventions, like AME, offer a developmentally appropriate and effective way to support parents and young children during treatment.
Feasibility and acceptability of a brief web‐based training on cognitive behavioral tools for educators
Authors: Coe‐Odess Sarah , Crocker John , Quist Rachel , Meldonian Marisa , Gordon Elizabeth , Wilhelm Sabine , Greenberg Jennifer L.
Published: February 2024

A youth mental health crisis has been exacerbated significantly by the COVID‐19 pandemic. Teachers are often front‐line support for students in need. Yet teachers themselves are struggling, making it difficult to help their students. Cognitive behavioral interventions (CBIs) have been shown to reduce mental health symptoms in school settings. Learning and implementing a psychological intervention, however, places undue burden on teachers who are already struggling. This project aimed to develop and assess the acceptability and feasibility of a brief, web‐based training for educators on cognitive behavioral tools that can be implemented in classrooms without additional psychological or practical burden. Attendees (n = 193) attended one of two 1‐h trainings on applying cognitive behavioural therapy (CBT) in classrooms. Attendees completed pre‐ and posttraining surveys on their knowledge and comfort using CBT. Following the course, attendees reported increases in knowledge and comfort using CBT skills, with large effect sizes. Attendees reported being highly satisfied with the course and likely to recommend the course to colleagues. Limitations of this work include a relatively small, homogenous sample and a low rate of completing both pre‐ and posttraining measures. Suggestions for future research include measuring change in practice as a result of the training. Implications of our findings are discussed.
Application of AlphaFold models in evaluating ligandable cysteines across E3 ligases
Authors: Koldenhof Patrick , Bemelmans Martijn P. , Ghosh Brahma , Damm‐Ganamet Kelly L. , van Vlijmen Herman W. T. , Pande Vineet
Published: February 2024

Proteolysis Targeting Chimeras (PROTACs) are an emerging therapeutic modality and chemical biology tools for Targeted Protein Degradation (TPD). PROTACs contain a ligand targeting the protein of interest, a ligand recruiting an E3 ligase and a linker connecting these two ligands. There are over 600 E3 ligases known so far, but only a handful have been exploited for TPD applications. A key reason for this is the scarcity of ligands binding various E3 ligases and the paucity of structural data available, which complicates ligand design across the family. In this study, we aim to progress PROTAC discovery by proposing a shortlist of E3 ligases that can be prioritized for covalent targeting by performing systematic structural ligandability analysis on a chemoproteomic dataset of potentially reactive cysteines across hundreds of E3 ligases. One of the goals of this study is to apply AlphaFold (AF) models for ligandability evaluations, as for a vast majority of these ligases an experimental structure is not available in the protein data bank (PDB). Using a combination of pocket features, AF model quality and additional aspects, we propose a shortlist of E3 ligases and corresponding cysteines that can be prioritized to potentially discover covalent ligands and expand the PROTAC toolbox.
Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions
Authors: Lim Iris , Masutani Taishi , Hashitani Hikaru , Chess‐Williams Russ , Sellers Donna
Published: February 2024

The aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre‐contracted with 5‐HT (100 μM). Upon generation of stable phasic contractions, PDE‐4 and PDE‐5 inhibitors were added cumulatively to separate tissues. PDE‐4 inhibitors, such as rolipram (10 nM and greater) and roflumilast (100 nM and greater), resulted in significant attenuation of ureteral contractile responses, while a higher concentration of piclamilast (1 μM and greater) was required to induce a significant depressant effect. The attenuation effect by rolipram was abolished by SQ22536 (100 μM). PDE‐5 inhibitors, such as sildenafil and tadalafil, were not nearly as effective and were only able to suppress the 5‐HT‐induced contractions at higher concentrations of 1 μM. Rolipram significantly enhanced the depressant effect of forskolin, while sodium nitroprusside‐induced attenuation of contractile responses remained unchanged in the presence of tadalafil. In summary, our study demonstrates that PDE‐4 inhibitors are effective in attenuating 5‐HT‐induced contractility in porcine distal ureteral tissues, while PDE‐5 inhibitors are less effective. These findings suggest that PDE‐4 inhibitors, such as rolipram, may hold promise as potential therapeutic agents for the treatment of ureteral disorders attributable to increased intra‐ureteral pressure.