bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated Molecular Characterization of Intraductal Papillary Mucinous Neoplasms: An NCI Cancer Moonshot Precancer Atlas Pilot Project
Authors: Semaan Alexander , Bernard Vincent , Wong Justin , Makino Yuki , Swartzlander Daniel B. , Rajapakshe Kimal I. , Lee Jaewon J. , Officer Adam , Schmidt Christian Max , Wu Howard H. , Scaife Courtney L. , Affolter Kajsa E. , Nachmanson Daniela , Firpo Matthew A. , Yip-Schneider Michele , Lowy Andrew M. , Harismendy Olivier , Sen Subrata , Maitra Anirban , Jakubek Yasminka A. , Guerrero Paola A. 
Published: September 2023

Abstract

Intraductal papillary mucinous neoplasms (IPMN) are cystic precursor lesions to pancreatic ductal adenocarcinoma (PDAC). IPMNs undergo multistep progression from low-grade (LG) to high-grade (HG) dysplasia, culminating in invasive neoplasia. While patterns of IPMN progression have been analyzed using multiregion sequencing for somatic mutations, there is no integrated assessment of molecular events, including copy-number alterations (CNA) and transcriptional changes that accompany IPMN progression. We performed laser capture microdissection on surgically resected IPMNs of varying grades of histologic dysplasia obtained from 23 patients, followed by whole-exome and whole-transcriptome sequencing. Overall, HG IPMNs displayed a significantly greater aneuploidy score than LG lesions, with chromosome 1q amplification being associated with HG progression and with cases that harbored co-occurring PDAC. Furthermore, the combined assessment of single-nucleotide variants (SNV) and CNAs identified both linear and branched evolutionary trajectories, underscoring the heterogeneity in the progression of LG lesions to HG and PDAC. At the transcriptome level, upregulation of MYC-regulated targets and downregulation of transcripts associated with the MHC class I antigen presentation machinery as well as pathways related to glycosylation were a common feature of progression to HG. In addition, the established PDAC transcriptional subtypes (basal-like and classical) were readily apparent within IPMNs. Taken together, this work emphasizes the role of 1q copy-number amplification as a putative biomarker of high-risk IPMNs, underscores the importance of immune evasion even in noninvasive precursor lesions, and reinforces that evolutionary pathways in IPMNs are heterogenous, comprised of both SNV and CNA-driven events.

Significance:
Integrated molecular analysis of genomic and transcriptomic alterations in the multistep progression of IPMNs, which are bona fide precursors of pancreatic cancer, identifies features associated with progression of low-risk lesions to high-risk lesions and cancer, which might enable patient stratification and cancer interception strategies.
Mental Health Conditions Among Children and Adolescents With Congenital Heart Disease: A Danish Population-Based Cohort Study
Authors: Miles Kimberley G. , Farkas Dóra Körmendiné , Laugesen Kristina , Sørensen Henrik Toft , Kasparian Nadine A. , Madsen Nicolas 
Published: September 2023

BACKGROUND:
Despite the known mental health burden among children with congenital heart disease (CHD), the literature is constrained by a lack of comparison cohorts and population-based follow-up data. We examined the incidence of mental health conditions among children with CHD, relative to 3 comparison cohorts.

METHODS:
This population-based cohort study identified all children with CHD (<18 years of age; n=16 473) in Denmark from 1996 to 2017, through linkage of individual-level data across national registries. This allowed for complete follow-up of the population. Comparison cohorts included children from the general population (n=162 204), siblings of children with CHD (n=20 079), and children with non-CHD major congenital anomalies (n=47 799). Mental health conditions were identified using inpatient and outpatient hospital discharge codes, prescription data, and data on use of community-based psychology, psychiatry, and psychotherapy services. We computed cumulative incidence by 18 years of age, incidence rates, and adjusted hazard ratios (aHRs) using Cox regression. aHRs accounted for sex, year of CHD diagnosis, parental mental health, and socioeconomic status. All estimates were stratified by age, sex, and CHD complexity.

RESULTS:
The cumulative incidence of mental health conditions by 18 years of age in the CHD cohort was 35.1% (95% CI, 34.0%–36.1%), corresponding to aHRs of 1.64 (95% CI, 1.58–1.71), 1.41 (95% CI, 1.30–1.52), and 1.02 (95% CI, 0.98–1.07) compared with the general population, sibling, and major congenital anomaly cohorts, respectively. Mental health incidence rates showed prominent peaks in early childhood and adolescence. Males and children with severe or single-ventricle CHD demonstrated higher incidence rates of mental health conditions relative to females and children with mild or moderate CHD, respectively. Compared with the general population and sibling cohorts, incidence rates and aHRs in the CHD cohort were highest for severe stress reactions, attention deficit/hyperactivity disorder, intellectual disability, and autism spectrum disorder. Compared with children in the major congenital anomaly cohort, the aHRs were close to 1.

CONCLUSIONS:
More than one-third of children with CHD were diagnosed or treated for a mental health condition by 18 years of age. Mental health conditions began early in life and were most prominent among males and children with severe or single-ventricle heart disease.
Comparisons of Rainfall Microphysical Characteristics between the Southeastern Tibetan Plateau and Low-Altitude Areas
Authors: Xu Xin , Chen Xuelong , Cao Dianbin , Liu Yajing , Li Luhan , Ma Yaoming 
Published: September 2023

Abstract
The low air pressure and density over the Tibetan Plateau may have an impact on the microphysical features of rainfall. Using a two-dimensional video disdrometer (2DVD), a Micro Rain Radar (MRR), and a microwave radiometer (MWR), the features of the raindrop size distribution (DSD) on the southeastern Tibetan Plateau (SETP) are explored and compared with those in low-altitude regions. The falling speed of raindrops on the SETP is higher than that in low-altitude areas. Under different rainfall-rate categories, the number concentration and the maximum diameter of raindrops on the SETP are smaller than those in low-altitude regions. The convective rainfall on the SETP is more maritime-like because the South Asian summer monsoon brings water vapor from the ocean here. For stratiform and convective rainfall, the SETP has more small-sized raindrops than low-altitude locations. The mass-weighted mean diameters (Dm) on the SETP are the smallest among six sites. The generalized intercept parameter (Nw) of stratiform rainfall is balanced at a low rainfall rate, while that of convective rainfall is balanced at a high rainfall rate. Furthermore, for a given μ (the shape parameter of gamma distribution) value, the λ (the slope parameter of gamma distribution) value on the SETP is the highest of the six sites.

Significance Statement
For the occurrence and progression of rainfall, microphysical processes (for instance, collision, fragmentation, coalescence, and evaporation) that take place when rainfall particles descend are crucial. A key factor in the microphysical features of rainfall that varies with rainfall rates and types is the raindrop size distribution (DSD). The southeastern Tibetan Plateau (SETP)’s unique terrain ensures that there is enough moisture for rain to fall there, but little is known about the microphysical aspects of this type of precipitation. There has not been enough research done on how the high altitude affects the microphysical features of rainfall. The microphysical features of rainfall in this area must thus be studied.
Sensitivity of Banner Cloud Formation to Orography and the Ambient Atmosphere: Transition from Idealized to More Realistic Scenarios
Authors: Thomas Marius Levin , Wirth Volkmar 
Published: September 2023

Abstract
Banner clouds are clouds in the lee of steep mountains or sharp ridges on otherwise cloud-free days. Previous studies investigated various aspects of banner cloud formation in numerical simulations, most of which were based on idealized orography and a neutrally stratified ambient atmosphere. The present study extends these simulations in two important directions by 1) examining the impact of various types of orography ranging from an idealized pyramid to the realistic orography of Mount Matterhorn and 2) accounting for an ambient atmosphere that turns from neutral to stably stratified below the mountain summit. Not surprisingly, realistic orography introduces asymmetries in the spanwise direction. At the same time, banner cloud occurrence remains associated with a coherent area of strong uplift, although this region does not have to be located exclusively in the lee of the mountain any longer. In the case of Mount Matterhorn with a westerly ambient flow, a large fraction of air parcels rises along the southern face of the mountain, before they reach the lee and are lifted into the banner cloud. The presence of a shallow boundary layer with its top below the mountain summit introduces more complex behavior compared to a neutrally stratified boundary layer; in particular, it introduces a dependence on wind speed, because strong wind is associated with strong turbulence that is able to raise the boundary layer height and, thus, facilitates the formation of a banner cloud.
The 1996 Mid-Atlantic Winter Flood: Exploring Climate Risk through a Storyline Approach
Authors: Pettett Abigail , Zarzycki Colin M. 
Published: September 2023

Abstract
This article explores the application of thermodynamic perturbations to a historical midlatitude, wintertime, rain-on-snow flood event to evaluate how similar events may evolve under different climate forcings. In particular, we generate a hindcast of the 1996 Mid-Atlantic flood using an ensemble of 14-km variable-resolution simulations completed with the U.S. Department of Energy’s global Energy Exascale Earth System Model (E3SM). We show that the event is skillfully reproduced over the Susquehanna River Basin (SRB) by E3SM when benchmarked against in situ observational data and high-resolution reanalyses. In addition, we perform five counterfactual experiments to simulate the flood under preindustrial conditions and four different levels of warming as projected by the Community Earth System Model Large Ensemble. We find a nonlinear response in simulated surface runoff and streamflow as a function of atmospheric warming. This is attributed to changing contributions of liquid water input from a shallower initial snowpack (decreased snowmelt), increased surface temperatures and rainfall rates, and increased soil water storage. Flooding associated with this event peaks from around +1 to +2 K of global average surface warming and decreases with additional warming beyond this. There are noticeable timing shifts in peak runoff and streamflow associated with changes in the flashiness of the event. This work highlights the utility of using storyline approaches for communicating climate risk and demonstrates the potential nonlinearities associated with hydrologic extremes in areas that experience ephemeral snowpack, such as the SRB.
The Study of Clinical Phenotypes and Analysis of Mutations in L1 Syndrome
Authors: Shrinivasamurthy Madhan , Benakanal Shreeshail V , Kakanahalli Nagaraj 
Published: September 2023

Background L1CAM protein plays a crucial role during early development and mutations in L1CAM cause L1 syndrome. L1 syndrome demonstrates a highly variable presentation within and between families. The clinical symptoms of L1 syndrome include mental retardation, hydrocephalus, spasticity, aphasia, and adducted thumb. Mutations in L1CAM gene were found to affect structurally essential key residues in extracellular region of L1 leading to changes in protein binding properties. In most cases, these mutations create unexpected phenotypes which need to be understood thoroughly. Purpose The L1 syndrome patients were identified by various phenotypes like mental retardation, hydrocephalus, aphasia, spasticity, adducted thumb, etc., and the patients or mental retardation (MR) children who had more than three symptoms. This study aimed to screen mutations in multiple exons by Sanger sequencing. Methods The present study employed primers which are designed for specific exons of L1CAM gene to amplify and sequence the amplified product to detect the mutations in L1 syndrome patients by the Sanger sequencing. Chi-square test was used to determine the mutation detection rate with the number of L1 syndrome phenotypes and several i n silico programs were used to investigate potential effects of the variants. Results The nine different mutations in six patients. The mutation detection rate was high (83.33%) in patients with more than one L1 syndrome phenotype and in patients with more than one affected member in a family compared to patients with single phenotypes and negative family history (16.6%). Conclusion The mutation detection rate was related to the presence of typical L1 syndrome phenotypes and the family history. Screening of L1CAM gene mutations in the Indian population is much needed to analyze the mutations and understand the mechanism underlying L1 disease. The present study has identified some novel mutations which are implicated in alterations in various biological functions during development leading to pathogenesis of L1 syndrome.
Case Series on Effectiveness of Cutting-Down Program for Managing Non-Suicidal Self-Injury Among Adolescents
Authors: Saxena Osheen , Kishore M. Thomas , Kumar Ajay , Sagar K. John Vijay , Binukumar B. 
Published: September 2023

Background: Non-suicidal self-injury (NSSI) is an emerging issue among adolescents with a growing prevalence in clinical settings. It is a multi-faceted condition in terms of psychiatric comorbidities, variation in the form and method of self-harm, body area, the pattern of the wound and the function served, and therefore, understanding and managing it adequately in routine clinical practice is a challenge. There is a need for research to focus on in-depth understanding of the effectiveness of and process issues for existing interventions for NSSI in adolescents. Aim: The present research is a case series aimed at examining the effectiveness of the cutting-down programme (CDP), a manualized cognitive behaviour therapy programme, in reducing the frequency and intensity of NSSI acts and urges in two adolescents. The objectives of the study were to examine the effect of the CDP on depressive symptoms, dysfunctional attitudes, emotion regulation, experiential avoidance and global functioning in adolescents with NSSI, and to explore the association of patient motivation and patient perception of therapy with therapy outcome in adolescents with NSSI. Method: For the study, two adolescents with NSSI who presented to the Department of Child and Adolescent Psychiatry, NIMHANS, Bangalore, were recruited using purposive sampling. They were assessed using the MINI-International Neuropsychiatric Interview for Children and Adolescents (MINI Kid Screen 7.0.2). In addition, standardized were used to assess the severity and functions of NSSI, borderline personality disorder, depression, emotion regulation skills, dysfunctional attitudes, psychological flexibility and global functioning. The participants were also assessed on a semi-structured interview to assess NSSI every week during the intervention. Baseline measures were repeated when the CDP was completed. Further, the non-specific factors such as patient’s perceptions of therapy and patient motivation were assessed using the standardized scales. Results: The CDP was found to be effective in reducing the NSSI among the two adolescents. It also improved their depressive symptoms, dysfunctional attitudes, emotion regulation, experiential avoidance and global functioning. The therapy outcome was related to the participants’ motivations and perceptions of therapy. Conclusion: The CDP is an effective intervention for reducing NSSI acts. However, client characteristics such as perception and motivation for therapy will play a role in therapy outcome.
Revision Rates After Primary Allograft ACL Reconstruction by Allograft Tissue Type in Older Patients
Authors: Engler Ian D. , Chang Audrey Y. , Kaarre Janina , Shannon Michael F. , Curley Andrew J. , Smith Clair N. , Hughes Jonathan D. , Lesniak Bryson P. , Musahl Volker 
Published: September 2023

Background: While there is extensive literature on the use of allograft versus autograft in anterior cruciate ligament (ACL) reconstruction, there is limited clinical evidence to guide the surgeon in choice of allograft tissue type. Purpose: To assess the revision rate after primary ACL reconstruction with allograft and to compare revision rates based on allograft tissue type and characteristics. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent primary allograft ACL reconstructions at a single academic institution between 2015 and 2019 and who had minimum 2-year follow-up were included. Exclusion criteria were missing surgical or allograft tissue type data. Demographics, operative details, and subsequent surgical procedures were collected. Allograft details included graft tissue type (Achilles, bone–patellar tendon–bone [BTB], tibialis anterior or posterior, semitendinosus, unspecified soft tissue), allograft category (all–soft tissue vs bone block), donor age, irradiation duration and intensity, and chemical cleansing process. Revision rates were calculated and compared by allograft characteristics. Results: Included were 418 patients (age, 39 ± 12 years; body mass index, 30 ± 9 kg/m2). The revision rate was 3% (11/418) at a mean follow-up of 4.9 ± 1.4 years. There were no differences in revision rate according to allograft tissue type across Achilles tendon (3%; 3/95), BTB (5%; 3/58), tibialis anterior or posterior (3%; 5/162), semitendinosus (0%; 0/46), or unspecified soft tissue (0%; 0/57) ( P = .35). There was no difference in revision rate between all–soft tissue versus bone block allograft (6/283 [2%] vs 5/135 [4%], respectively; P = .34). Of the 51% of grafts with irradiation data, all grafts were irradiated, with levels varying from 1.5 to 2.7 Mrad and 82% of grafts having levels of <2.0 Mrad. There was no difference in revision rate between the low-dose and medium-to high-dose irradiation cohorts (4% vs 6%, respectively; P = .64). Conclusion: Similarly low (0%-6%) revision rates after primary ACL reconstruction were seen regardless of allograft tissue type, bone block versus all-soft tissue allograft, and sterilization technique in 418 patients with mean age of 39 years. Surgeons may consider appropriately processed allograft tissue with or without bone block when indicating ACL reconstruction in older patients.
Phase 3 SELENE study: ibrutinib plus BR/R-CHOP in previously treated patients with follicular or marginal zone lymphoma
Authors: Nastoupil Loretta J. , Hess Georg , Pavlovsky Miguel A. , Danielewicz Iwona , Freeman Jane , García-Sancho Alejandro Martin , Glazunova Valeria , Grigg Andrew , Hou Jing-Zhou , Janssens Ann , Kim Seok Jin , Masliak Zvenyslava , McKay Pam , Merli Francesco , Munakata Wataru , Nagai Hirokazu , Özcan Muhit , Preis Meir , Wang Tingyu , Rowe Melissa , Tamegnon Monelle , Qin Rui , Henninger Todd , Curtis Madeliene , Caces Donne Bennett , Thieblemont Catherine , Salles Gilles 
Published: September 2023

Abstract
The phase 3 SELENE study evaluated ibrutinib + chemoimmunotherapy (CIT; bendamustine and rituximab [BR]; or rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone [R-CHOP]) for patients with relapsed/refractory (R/R) follicular lymphoma (FL) or marginal zone lymphoma (MZL). Adult patients who had received ≥1 prior line of CIT were randomized 1:1 to oral ibrutinib (560 mg) or placebo daily, plus 6 cycles of BR/R-CHOP. The primary end point was investigator-assessed progression-free survival (PFS). Overall, 403 patients were randomized to ibrutinib + CIT (n = 202) or placebo + CIT (n = 201). Most patients received BR (90.3%) and had FL (86.1%). With a median follow-up of 84 months, median PFS was 40.5 months in the ibrutinib + CIT arm and 23.8 months in the placebo + CIT arm (hazard ratio [HR], 0.806; 95% confidence interval [CI], 0.626-1.037; P = .0922). Median overall survival was not reached in either arm (HR, 0.980; 95% CI, 0.686-1.400). Grade ≥3 treatment-emergent adverse events (TEAEs) were reported in 85.6% and 75.4% of patients in the ibrutinib + CIT and placebo + CIT arms, respectively. In each arm, 13 patients had TEAEs leading to death. The addition of ibrutinib to CIT did not significantly improve PFS compared with placebo + CIT. The safety profile was consistent with known profiles of ibrutinib and CIT. This trial was registered at www.clinicaltrials.gov as #NCT01974440.
Prognostic model using 18F-FDG PET radiomics predicts progression-free survival in relapsed/refractory Hodgkin lymphoma
Authors: Driessen Julia , Zwezerijnen Gerben J. C. , Schöder Heiko , Kersten Marie José , Moskowitz Alison J. , Moskowitz Craig H. , Eertink Jakoba J. , Heymans Martijn W. , Boellaard Ronald , Zijlstra Josée M. 
Published: September 2023

Abstract
Investigating prognostic factors in patients with relapsed or primary refractory classical Hodgkin lymphoma (R/R cHL) is essential to optimize risk-adapted treatment strategies. We built a prognostic model using baseline quantitative 18F-fluorodeoxyglucose positron emission tomography (PET) radiomics features and clinical characteristics to predict the progression-free survival (PFS) among patients with R/R cHL treated with salvage chemotherapy followed by autologous stem cell transplantation. Metabolic tumor volume and several novel radiomics dissemination features, representing interlesional differences in distance, volume, and standard uptake value, were extracted from the baseline PET. Machine learning using backward selection and logistic regression were applied to develop and train the model on a total of 113 patients from 2 clinical trials. The model was validated on an independent external cohort of 69 patients. In addition, we validated 4 different PET segmentation methods to calculate radiomics features. We identified a subset of patients at high risk for progression with significant inferior 3-year PFS outcomes of 38.1% vs 88.4% for patients in the low-risk group in the training cohort (P &lt; .001) and 38.5% vs 75.0% in the validation cohort (P = .015), respectively. The overall survival was also significantly better in the low-risk group (P = .022 and P &lt; .001). We provide a formula to calculate a risk score for individual patients based on the model. In conclusion, we developed a prognostic model for PFS combining radiomics and clinical features in a large cohort of patients with R/R cHL. This model calculates a PET-based risk profile and can be applied to develop risk-stratified treatment strategies for patients with R/R cHL. These trials were registered at www.clinicaltrials.gov as #NCT02280993, #NCT00255723, and #NCT01508312.