bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffuse myocardial fibrosis is uncommon in people with perinatally acquired human immunodeficiency virus infection
Authors: Williams Jason L. , Hung Frances , Jenista Elizabeth , Barker Piers , Chakraborty Hrishikesh , Kim Raymond , McCrary Andrew W. , Shah Svati H. , Thielman Nathan , Bloomfield Gerald S. 
Published: March 2024

Abstract
Background
Cardiovascular disease (CVD) remains a leading cause of death in people living with HIV. Myocardial fibrosis is well-described in HIV infection acquired in adulthood. We evaluate the burden of fibrosis by cardiac magnetic resonance in people with perinatal HIV infection.

Methods
Individuals with perinatally acquired HIV (pnHIV) diagnosed before 10 years-old and on antiretroviral treatment for ≥ 6 months were matched with uninfected controls. Patients with significant cardiometabolic co-morbidities and pregnancy were excluded. Diffuse fibrosis was assessed by cardiac magnetic resonance (CMR) with native T1 mapping for calculation of extracellular volume fraction (ECV). Viability was assessed with late gadolinium enhancement. The normality of fibrosis was assessed using the Komogrov-Smirnov test. Fibrosis between the groups was analyzed using a Mann-Whitney U test, as the data was not normally distributed. Statistical significance was defined as a p-valve < 0.05.

Results
Fourteen adults with pnHIV group and 26 controls (71% female and 86% Black race) were assessed. The average (± standard deviation) age in the study group was 29 (± 4.3) years-old. All pnHIV had been on ART for decades. Demographic data, CMR functional/volumetric data, and pre-contrast T1 mapping values were similar between groups. Diastolic function was normal in 50% of pnHIV patients and indeterminate in most of the remainder (42%). There was no statistically significant difference in ECV between groups; p = 0.24.

Conclusion
Perinatally-acquired HIV was not associated with diffuse myocardial fibrosis. Larger prospective studies with serial examinations are needed to determine whether pnHIV patients develop abnormal structure or function more often than unaffected controls.
Multicenter analysis on the value of standard (chemo)radiotherapy in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction
Authors: Bostel Tilman , Nikolaidou Eirini , Wollschläger Daniel , Mayer Arnulf , Kaufmann Justus , Hopprich Anne , Rühle Alexander , Grosu Anca-Ligia , Debus Jürgen , Fottner Christian , Moehler Markus , Grimminger Peter , Schmidberger Heinz , Nicolay Nils Henrik 
Published: March 2024

Abstract
Background
To assess the tolerability and oncological results of chemoradiation in elderly patients with locally advanced adenocarcinoma of the esophagus or gastroesophageal junction.

Methods
This multi-center retrospective analysis included 86 elderly patients (≥ 65 years) with esophageal or gastroesophageal junction adenocarcinoma (median age 73 years; range 65–92 years) treated with definitive or neoadjuvant (chemo)radiotherapy. The treatment was performed at 3 large comprehensive cancer centers in Germany from 2006 to 2020. Locoregional control (LRC), progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), and treatment-associated toxicities according to CTCAE criteria v5.0 were analyzed, and parameters potentially relevant to patient outcomes were evaluated.

Results
Thirty-three patients (38%) were treated with neoadjuvant chemoradiation followed by surgery, while the remaining patients received definitive (chemo)radiation. The delivery of radiotherapy without dose reduction was possible in 80 patients (93%). In 66 patients (77%), concomitant chemotherapy was initially prescribed; however, during the course of therapy, 48% of patients (n = 32) required chemotherapy de-escalation due to treatment-related toxicities and comorbidities. Twenty-nine patients (34%) experienced higher-grade acute toxicities and 14 patients (16%) higher-grade late toxicities. The 2-year LRC, DMFS, PFS, and OS amounted to 72%, 49%, 46%, and 52%, respectively. In multivariate analysis, neoadjuvant chemoradiation followed by surgery was shown to be associated with significantly better PFS (p = 0.006), DMFS (p = 0.006), and OS (p = 0.004) compared with all non-surgical treatments (pooled definitive radiotherapy and chemoradiation). No such advantage was seen over definitive chemoradiation. The majority of patients with neoadjuvant therapy received standard chemoradiotherapy without dose reduction (n = 24/33, 73%). In contrast, concurrent chemotherapy was only possible in 62% of patients undergoing definitive radiotherapy (n = 33/53), and most of these patients required dose-reduction or modification of chemotherapy (n = 23/33, 70%).

Conclusions
In our analysis, omission of chemotherapy or adjustment of chemotherapy dose during definitive radiotherapy was necessary for the overwhelming majority of elderly esophageal cancer patients not eligible for surgery, and hence resulted in reduced PFS and OS. Therefore, optimization of non-surgical approaches and the identification of potential predictive factors for safe administration of concurrent chemotherapy in elderly patients with (gastro)esophageal adenocarcinoma is required.
The health-care utilization and economic burden in patients with genetic skeletal disorders
Authors: Liu Luna , Shi Yingzhou , Fan Xiude , Yao Yangyang , Wu Wanhong , Tian Yang , Wu Huixiao , Li Zongyue , Wang Yanzhou , Xu Chao 
Published: March 2024

Abstract
Background
Most genetic skeletal disorders (GSD) were complex, disabling and life-threatening without effective diagnostic and treatment methods. However, its impacts on health system have not been well studied. The study aimed to systematically evaluate the health-care utilization and economic burden in GSD patients.

Methods
The patients were derived from 2018 Nationwide Inpatient Sample and Nationwide Readmissions Database. GSD patients were extracted based on International Classification of Diseases-10th revision codes.

Results
A total of 25,945 (0.12%) records regarding GSD were extracted from all 21,400,282 records in NIS database. GSD patients were likely to have significantly longer length of stay (6.50 ± 0.08 vs. 4.63 ± 0.002, P < 0.001), higher total charges ($85,180.97 ± 1,239.47 vs. $49,884.26 ± 20.99, P < 0.001), suffering more procedure, diagnosis and transferring records in comparison to patients with common conditions. GSD patients had a significantly higher 30-day all-cause readmission rate based on Nationwide Readmissions Database.

Conclusions
The heavy health-care utilization and economic burden emphasized the urgency for policy leaders, scientific and pharmaceutical researchers, health care providers and employers to identify innovative ways and take effective measurements immediately, and eventually to help improve the care, management, and treatment of these devastating diseases.
Surgeons’ knowledge regarding perioperative pain management in patients with opioid use disorder: a survey among 260 members of the American College of Surgeons
Authors: Burgess Jessica R. , Heneghan Kathleen C. , Barot Tarra G. , Stulberg Jonah J. 
Published: March 2024

Abstract
Background
Patients with opioid use disorder (OUD) are increasing, challenging surgeons to adjust post-operative pain management guidelines. A literature review identified limited information on how to best care for these patients. The purpose of this study was to determine surgical perioperative management of OUD, challenges, and support needed for optimal care.

Methods
This study utilized an anonymous voluntary survey that was distributed to members of the American College of Surgeons through the association’s electronic weekly newsletter. The survey was advertised weekly for three consecutive weeks. The survey included questions regarding surgeons’ management of perioperative pain in patients with opioid use disorder and perceived barriers in treatment.

Results
A total of 260 surgeons responded representing all specialties except ophthalmology. General surgery (66.5%) and plastic and reconstructive surgery (7.5%) represented the majority of responders. Ninety-five percent of surgeons reported treating a patient who used opioids in the past month and 86% encountered a patient with OUD. Nearly half (46%) reported being uncomfortable managing postoperative pain in patients with OUD. Most (67%) were not aware of any guidelines or standards pertaining to perioperative management of patients with OUD. While consultation was sought by 86% of surgeons, analyses identified lack of timely response and a lack of care coordination among specialists. Lack of knowledge and fear of harm (contributing further to addiction) were the most common themes.

Conclusion
Nearly half of surgeons report discomfort caring for patients with OUD with the vast majority involving a consulting service to assist with their care. Most surgeons believe that it would be helpful to have guidelines regarding the care of these patients. This provides an opportunity for increased education and training on the perioperative management of patients with OUD and further collaboration with addiction medicine, psychiatry and pain management colleagues.
A risk analysis of alpelisib-induced hyperglycemia in patients with advanced solid tumors and breast cancer
Authors: Rodón Jordi , Demanse David , Rugo Hope S. , Burris Howard A. , Simó Rafael , Farooki Azeez , Wellons Melissa F. , André Fabrice , Hu Huilin , Vuina Dragica , Quadt Cornelia , Juric Dejan 
Published: March 2024

Abstract
Background
Hyperglycemia is an on-target effect of PI3Kα inhibitors. Early identification and intervention of treatment-induced hyperglycemia is important for improving management of patients receiving a PI3Kα inhibitor like alpelisib. Here, we characterize incidence of grade 3/4 alpelisib-related hyperglycemia, along with time to event, management, and outcomes using a machine learning model.

Methods
Data for the risk model were pooled from patients receiving alpelisib ± fulvestrant in the open-label, phase 1 X2101 trial and the randomized, double-blind, phase 3 SOLAR-1 trial. The pooled population (n = 505) included patients with advanced solid tumors (X2101, n = 221) or HR+/HER2− advanced breast cancer (SOLAR-1, n = 284). External validation was performed using BYLieve trial patient data (n = 340). Hyperglycemia incidence and management were analyzed for SOLAR-1.

Results
A random forest model identified 5 baseline characteristics most associated with risk of developing grade 3/4 hyperglycemia (fasting plasma glucose, body mass index, HbA1c, monocytes, age). This model was used to derive a score to classify patients as high or low risk for developing grade 3/4 hyperglycemia. Applying the model to patients treated with alpelisib and fulvestrant in SOLAR-1 showed higher incidence of hyperglycemia (all grade and grade 3/4), increased use of antihyperglycemic medications, and more discontinuations due to hyperglycemia (16.7% vs. 2.6% of discontinuations) in the high- versus low-risk group. Among patients in SOLAR-1 (alpelisib + fulvestrant arm) with PIK3CA mutations, median progression-free survival was similar between the high- and low-risk groups (11.0 vs. 10.9 months). For external validation, the model was applied to the BYLieve trial, for which successful classification into high- and low-risk groups with shorter time to grade 3/4 hyperglycemia in the high-risk group was observed.

Conclusions
A risk model using 5 clinically relevant baseline characteristics was able to identify patients at higher or lower probability for developing alpelisib-induced hyperglycemia. Early identification of patients who may be at higher risk for hyperglycemia may improve management (including monitoring and early intervention) and potentially lead to improved outcomes.
Registration: ClinicalTrials.gov: NCT01219699 (registration date: October 13, 2010; retrospectively registered), ClinicalTrials.gov: NCT02437318 (registration date: May 7, 2015); ClinicalTrials.gov: NCT03056755 (registration date: February 17, 2017).
A proof of concept phase II study with the PDE-4 inhibitor roflumilast in patients with mild cognitive impairment or mild Alzheimer’s disease dementia (ROMEMA): study protocol of a double-blind, randomized, placebo-controlled, between-subjects trial
Authors: Possemis Nina , Verhey Frans , Prickaerts Jos , Blokland Arjan , Ramakers Inez 
Published: March 2024

Abstract

Background
Research into the neurobiological underpinnings of learning and memory has demonstrated the cognitive-enhancing effects associated with diverse classes of phosphodiesterase (PDE) inhibitors. Specific PDE inhibitors have been identified to improve neuronal communication through selective inhibition of PDE activity. Roflumilast, a PDE4 inhibitor, has demonstrated efficacy in enhancing episodic memory in healthy adults and elderly participants with pronounced memory impairment, indicative of amnestic mild cognitive impairment (aMCI). In alignment with these findings, the present protocol aims to provide a proof of concept phase II of the potential of roflumilast to aid patients diagnosed with (a)MCI or mild Alzheimer’s disease (AD) dementia.

Methods
The study will be conducted according to a double-blind, randomized placebo-controlled, between-subjects design. Participants with (a)MCI and mild AD dementia will be recruited through the Memory Clinic at the Maastricht University Medical Centre + (MUMC +) in Maastricht, the Netherlands, alongside outreach through regional hospitals, and social media. The study will have three arms: placebo, 50 μg roflumilast, and 100 μg roflumilast, with a treatment duration of 24 weeks. The primary outcome measure will focus on the assessment of episodic memory, as evaluated through participants’ performance on the 15-word Verbal Learning Task (VLT). Our secondary objectives are multifaceted, including an exploration of various cognitive domains. In addition, insights into the well-being and daily functioning of participants will be investigated through interviews with both the participants and their (informal) caregivers, we are interested in the well-being and daily functioning of the participants.

Discussion
The outcomes of the present study aim to elucidate the significance of the PDE4 inhibition mechanism as a prospective therapeutic target for enhancing cognitive function in individuals with (a)MCI and mild AD dementia. Identifying positive effects within these patient cohorts could extend the relevance of this treatment to encompass a broader spectrum of neurological disorders.

Trial registration
The Medical Ethics Committee of MUMC + granted ethics approval for the 4th version of the protocol on September 10th, 2020. The trial was registered at the European Drug Regulatory Affairs Clinical Trials (EudraCT) registered on the 19th of December 2019 (https://www.clinicaltrialsregister.eu/ctr-search/trial/2019-004959-36/NL) and ClinicalTrial.gov (NCT04658654, https://clinicaltrials.gov/study/NCT04658654?intr=roflumilast&cond=mci&rank=1) on the 8th of December 2020. The Central Committee on Research Involving Human Subjects (CCMO) granted approval on the 30th of September 2020.
Surgical repair of tetralogy of Fallot in a 78-year-old woman: a case report
Authors: Katayama Yuzo , Isobe Sho , Ozawa Tsukasa , Fujii Takeshiro 
Published: March 2024

Abstract
Background
Tetralogy of Fallot is a congenital heart disease mostly diagnosed and treated in early childhood. However, there are some adult cases receiving treatment.

Case presentation
We describe a 78-year-old Japanese woman who presented with severely hypertrophic right ventricle, ventricular septum defect, overriding aorta, and severe infundibular stenosis in the right ventricular outflow tract. As hypoxemia was mild and daily exertion was sufficiently possible, home oxygen therapy was introduced. After 1 month, she was referred because of a positive blood culture. The blood culture test was positive four times, therefore, the antibacterial drug was administered according to active infective endocarditis. SpO2 repeatedly decreased during hospitalization, thus oxygen was needed. As there were infective endocarditis onset and progressive hypoxemia, we planned a surgical correction.

Conclusion
Tetralogy of Fallot was diagnosed and successfully treated with complete surgical correction, and the development of infective endocarditis was the definitive indication for surgery at this late age.
Fixed point theorem and iterated function system in φ-metric modular space
Authors: Acharjee Bikramjit , M Guru Prem Prasad 
Published: March 2024

AbstractWe introduce and study the concept of φ-metric modular space and, then define φ-α-Meir-Keeler contraction on it and explore its fixed point. Further, we define the Hausdorff distance between two non-empty compact subsets of the considered space. Some topological properties of φ-metric modular space are also explored. Additionally, we prove the existence of the attractor (fractal) of the IFS consisting of φ-α-Meir-Keeler contractions.
LRRK2 kinase inhibition reverses G2019S mutation-dependent effects on tau pathology progression
Authors: Lubben Noah , Brynildsen Julia K. , Webb Connor M. , Li Howard L. , Leyns Cheryl E. G. , Changolkar Lakshmi , Zhang Bin , Meymand Emily S. , O’Reilly Mia , Madaj Zach , DeWeerd Daniella , Fell Matthew J. , Lee Virginia M. Y. , Bassett Dani S. , Henderson Michael X. 
Published: March 2024

Abstract
Background
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson’s disease (PD). These mutations elevate the LRRK2 kinase activity, making LRRK2 kinase inhibitors an attractive therapeutic. LRRK2 kinase activity has been consistently linked to specific cell signaling pathways, mostly related to organelle trafficking and homeostasis, but its relationship to PD pathogenesis has been more difficult to define. LRRK2-PD patients consistently present with loss of dopaminergic neurons in the substantia nigra but show variable development of Lewy body or tau tangle pathology. Animal models carrying LRRK2 mutations do not develop robust PD-related phenotypes spontaneously, hampering the assessment of the efficacy of LRRK2 inhibitors against disease processes. We hypothesized that mutations in LRRK2 may not be directly related to a single disease pathway, but instead may elevate the susceptibility to multiple disease processes, depending on the disease trigger. To test this hypothesis, we have previously evaluated progression of α-synuclein and tau pathologies following injection of proteopathic seeds. We demonstrated that transgenic mice overexpressing mutant LRRK2 show alterations in the brain-wide progression of pathology, especially at older ages.

Methods
Here, we assess tau pathology progression in relation to long-term LRRK2 kinase inhibition. Wild-type or LRRK2G2019S knock-in mice were injected with tau fibrils and treated with control diet or diet containing LRRK2 kinase inhibitor MLi-2 targeting the IC50 or IC90 of LRRK2 for 3–6 months. Mice were evaluated for tau pathology by brain-wide quantitative pathology in 844 brain regions and subsequent linear diffusion modeling of progression.

Results
Consistent with our previous work, we found systemic alterations in the progression of tau pathology in LRRK2G2019S mice, which were most pronounced at 6 months. Importantly, LRRK2 kinase inhibition reversed these effects in LRRK2G2019S mice, but had minimal effect in wild-type mice, suggesting that LRRK2 kinase inhibition is likely to reverse specific disease processes in G2019S mutation carriers. Additional work may be necessary to determine the potential effect in non-carriers.

Conclusions
This work supports a protective role of LRRK2 kinase inhibition in G2019S carriers and provides a rational workflow for systematic evaluation of brain-wide phenotypes in therapeutic development.
Beyond STEM attrition: changing career plans within STEM fields in college is associated with lower motivation, certainty, and satisfaction about one’s career
Authors: Rosenzweig Emily Q. , Chen Xiao-Yin , Song Yuchen , Baldwin Amy , Barger Michael M. , Cotterell Michael E. , Dees Jonathan , Injaian Allison S. , Weliweriya Nandana , Walker Jennifer R. , Wiegert Craig C. , Lemons Paula P. 
Published: March 2024

Abstract
Background
Research and policy often focus on reducing attrition from educational trajectories leading to careers in science, technology, engineering, and mathematics (STEM), but many students change career plans within STEM. This study examined how changing career plans within STEM fields was associated with psychological indicators of career readiness. We conducted a large online survey of undergraduate students (N = 1,727) across 42 courses covering every major STEM discipline at a large U.S. research-intensive public university. Students reported about their career plans, whether plans had changed, motivation for those career plans, and satisfaction with and certainty of persisting with those plans. A trained team of coders classified whether students reported having STEM career plans at the time of the survey and at the beginning of college.

Results
Students who said they had changed career plans within STEM fields during college also reported lower motivation for their new career plans, satisfaction with those plans, and certainty of persisting in them, compared to students who retained consistent STEM career plans. With few exceptions, these associations held across students’ gender, race, year in school, and STEM field of study. Within-STEM career plan changes were very common, reported by 55% of fourth-year STEM students. Women reported changing career plans within STEM fields more often than men.

Implications
Results suggest that changing career plans within STEM is an important phenomenon to consider in preparing a qualified and diverse STEM workforce. Students who change career plans within STEM fields may need additional supports for their career motivation and satisfaction compared to students who do not change plans.
Potential use of Ulva intestinalis-derived biochar adsorbing phosphate ions in the cultivation of winter wheat Tristicum aestivum
Authors: Niedzbała Natalia , Lorenc-Grabowska Ewa , Rutkowski Piotr , Chęcmanowski Jacek , Szymczycha-Madeja Anna , Wełna Maja , Michalak Izabela 
Published: March 2024

AbstractIn this work, the properties of biochar produced from green macroalga Ulva intestinalis by pyrolysis were studied at temperatures of 300, 500, and 700 °C. This biochar was characterized in terms of multielemental composition, BET surface area, total pore volume, and biosorption properties toward phosphate ions. Biochar produced at 700 °C–25 m2/g had the highest surface area. The kinetics and isotherms of sorption processes of phosphate ions as sorbate by these sorbents were investigated. Modified biochar was able to remove 84.3% of phosphate ions from wastewater, whereas non-modified biochar—only 40.6%. Hence, biochar enriched with phosphate ions can serve as a valuable soil amendment. Pot experiments performed on winter wheat (Triticum aestivum) with a 3% addition of dry Ulva intestinalis, pristine biochar, and Mg-modified biochar enriched with phosphate ions showed that these amendments stimulated plant growth (length and fresh weight of plants) as well as enlarging the chlorophyll content in leaves. Our results indicate that the production of biochar (pristine and Mg-impregnated) is a sustainable option to valorize the biomass of seaweeds, and to recycle phosphorus from wastewater.
Graphical Abstract