bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term Effects of COVID-19 on Vascular Parameters—A Prospective Longitudinal Ultrasound Clinical Study
Authors: Chen James , Smith Kane , Xu Qian , Ali T’shura , Cavallazzi Rodrigo , Ghafghazi Shahab , Clifford Sean P. , Arnold Forest W. , Kong Maiying , Huang Jiapeng 
Published: May 2024

Objective: To investigate the longitudinal effects of COVID-19 on major vascular structures and parameters and clinical outcomes. Design: Observational prospective trial. Setting: Post-COVID-19 research clinic established by University of Louisville Division of Infectious Diseases. Participants: The study population consisted of 72 post-COVID-19 individuals and 11 non-COVID-19 infected participants in the control group. The participants were recruited from adult hospitals and from the community. The enrollment started in October 2020 and follow-up periods were at 3, 6, and 12 months from their initial COVID-19 diagnosis. Interventions: The participants were interviewed for medical and COVID-19 infection history. Samples of white blood cell (WBC), C-reactive protein (CRP), and D-dimer were taken at each visit. Certified sonographers performed vascular ultrasound on the study participants. Measurements and Main Results: Median intima-media thickness (IMT) was increased in mild/asymptomatic (0.80 mm) and severe/critical (0.90 mm) groups when compared with controls (0.60 mm; P < .001 for both groups). In the asymptomatic/mild group, 6-month median IMT (0.88 mm) was increased, compared with the 3-month group (0.75 mm), with P = .026. Increased age was associated with decreased mean arterial blood velocities (cm/s): common carotid ( r = −0.236, P = .032), internal carotid ( r = −0.208, P = .048), and subclavian artery mean velocity ( r = −0.357, P = .003). We did not find any instance of deep vein thrombosis. Median D-dimer, CRP, and WBC in the control group differed from asymptomatic/mild COVID-19 group ( P = .026, .011, and .003, respectively). Moreover, WBC in the asymptomatic/mild group and moderate COVID-19 group differed from severe/critical group ( P = .025 and P = .027, respectively); CRP also differed between asymptomatic/mild group and severe/critical group ( P = .014). Conclusions: There were differences in intima-media lumen thickness (IMT), arterial velocities, and inflammatory markers in post-COVID-19 patients. There was no instance of deep vein thrombosis in this post-COVID-19 study cohort. The increased IMT might infer atherosclerosis, which has shown to increase cardiovascular risks. It is not yet known whether the increase in IMT due to COVID should be treated in the same way as non-COVID-19 atherosclerosis—through statins, for example—or whether regular cardiovascular risk reduction would be useful. Clinical trial and mechanistic studies should be performed to further our understanding of COVID-19-related vascular pathologies.
The role of clinical breast examination and fine needle aspiration cytology in early detection of breast cancer: A cross-sectional study nested in a cohort in a low-resource setting
Authors: Mremi Alex , Pallangyo Angela , Mshana Thadeus , Mashauri Onstard , Kimario Walter , Nkya Gilbert , Mwakyembe Theresia Edward , Mollel Edson , Amsi Patrick , Mmbaga Blandina Theophil 
Published: May 2024

Background: Breast cancer is prevalent worldwide, with disparities in screening, diagnosis, treatment outcomes, and survival. In Africa, the majority of women are diagnosed at advanced stages, affecting treatment outcomes. Screening is one of the best strategies to reduce mortality rates caused by this cancer. Yet in a resource-constrained setting, there is limited access to screening and early detection services, which are available only at a few referral hospitals. Objectives: We aimed to evaluate the prevalence and screening results of breast cancer using clinical breast examination coupled with fine needle aspiration cytology in a resource-constraint setting. Design: A combined cross-sectional and cohort study. Methods: Women at risk of developing breast cancer in the Kilimanjaro region of Tanzania were invited, through public announcements, to their primary healthcare facilities. A questionnaire was used to assess the participants’ characteristics. The women received a clinical breast examination, and detectable lesions were subjected to a confirmatory fine needle aspiration cytology or an excisional biopsy. Preliminary data from this ongoing breast cancer control program were extracted and analyzed for this study. Results: A total of 3577 women were screened for breast cancer; their mean age was 47 ± 7.53 years. About a third of them (1145, 32%) were practicing self-breast examination at least once a month. Of 200 (5.6%) with abnormal clinical breast examination, 18 (9%) were confirmed to be breast cancer, making the prevalence to be 0.5%. The vast majority of participants with breast cancer (13, 72.2%) had early disease stages, and infiltrating ductal carcinoma, no special type, was the most common (15, 83.3%) histopathology subtype. Hormonal receptor status determination results indicated that 11 (61.1%), 7 (38.9%), and 5 (27.8%) of the tumors overexpressed estrogen receptor, progesterone receptor, and human epidermal receptor-2, respectively. Conclusion: Our study demonstrates 5.6% of Tanzanian women have abnormal clinical breast examination findings, with 9% having breast cancer. Nearly three-quarters (72.2%) of breast cancer screened for early disease were detected in the early disease stages. This finding suggests that organized screening with clinical breast examination coupled with fine needle aspiration cytology, which is a simple and cost-effective screening method, has the potential to improve early detection and outcomes for breast cancer patients in a resource-constraint setting.
Primary Human Papillomavirus Test Uptake and Cervical Cancer Screening Trends in the Midwest, United States
Authors: Ehman Katie M. , Jenkins Gregory D. , Grimm Jessica A. , Cammack Taylor L. , Samuelson Brittanee J. , Stoll Rebecca J. , Maxson Julie A. , MacLaughlin Kathy L. 
Published: May 2024

Introduction/Objectives: Despite U.S. Preventive Services Task Force and American Cancer Society endorsement of primary HPV screening, limited published data shows low uptake. Primary Aim: Assess cervical cancer screening rates over time, particularly primary HPV test uptake, among patients in a midwestern practice. Secondary Aim: Evaluate associations between sociodemographics and screening adherence. Methods: Cross-sectional study. Qualifying subjects and type of screening test used were identified by applying ICD-9, ICD-10, lab test, and CPT codes to the Unified Data Platform. Sociodemographics were found through the electronic health record. Results: Primary HPV uptake represented <1% of annual screening from 1/2017 to 1/2022. On 1/1/2022, only 55% of 21 to 29 year old and 63% of 30 to 65 year old were up to date with screening among the studied population. For 21 to 29 year old, compared with White women, Black women were 28% less likely to be screened [RR = 0.72 (0.66-0.79)]. Compared with never-smokers, current smokers were 9% less likely to be screened [RR = 0.91 (0.87-0.96)], past smokers were 14% more likely [RR = 1.14 (1.09-1.2)]. Among 30 to 65 year old, compared with White women, Black women were 14% less likely to be screened [RR = 0.86 (0.81-0.9)]. Compared with never-smokers, current smokers were 21% less likely to be screened [RR = 0.79 (0.77-0.81)], past smokers were 6% less likely [RR = 0.94 (0.92-0.95)]. Jointly considering race, ethnicity, smoking status, Charlson score, and rurality, findings were similar for 21 to 29 year old; Black women were screened less than White women [RR = 0.73 (0.67-0.79)]; current smokers [RR = 0.9 (0.85-0.94)] and past smokers [RR = 1.12 (1.06-1.17)] were screened less than never smokers. For 30 to 65 year old, Black women were screened less than White women [RR = 0.83 (0.79-0.88)]; current smokers [RR = 0.8 (0.78-0.81)] and past smokers [RR = 0.95 (0.93-0.96)] were screened less than never smokers. Conclusions: Screening rates remained below the Healthy People 2030 goal of 79.2% over time, particularly for younger Black women and current smokers, with minimal use of primary HPV screening.
Outcomes of New York City Care Calls: A Prospective Randomized Controlled Effectiveness Trial of Telephone-Delivered Type 2 Diabetes Self-Management Support
Authors: Gonzalez Jeffrey S. , Hoogendoorn Claire J. , Schechter Clyde B. , Pappalardo Lindsey , Fernandez Galvis Maria A. , Linnell Jill , Pham-Singer Hang , Walker Elizabeth A. , Wu Winfred Y. 
Published: May 2024

Purpose: The purpose of the 12-month randomized controlled trial was to evaluate the effectiveness of a Telephonic Self-Management Support (T-SMS) program among adults with type 2 diabetes (T2D). Methods: Eight hundred twelve adults with T2D participated in NYC Care Calls (mean age = 59.2, SD = 10.8; female = 57%; mean A1C = 9.3, SD = 1.8; Latino = 86%) and were randomly assigned to T-SMS or enhanced usual care (EUC). A1C (primary outcome), blood pressure, and body mass index (secondary outcomes) were extracted from electronic medical records. Secondary patient-reported outcomes, including depressive symptoms, diabetes distress, medication adherence, and self-management activities, were assessed by telephone in English or Spanish. For T-SMS, the number of assigned phone calls was based on baseline A1C, depressive symptoms, and/or diabetes distress. Analyses were conducted under the intention-to-treat principle. Results: A1C decreased over 12 months in both T-SMS (0.72% percentage points; 95% CI, 0.53-0.91) and EUC (0.66% percentage points; 95% CI, 0.46-0.85; Ps < .001). Diabetes distress and self-management also improved over time in both arms ( Ps < .05). Compared to EUC, participants in the T-SMS arm did not differ in outcomes. Conclusions: The T-SMS and EUC groups were found not to have an appreciable outcome difference. It is unclear whether improvements in A1C across both conditions represent a secular trend or indicate that print-based educational intervention may have a positive impact on self-management and well-being.
Immediate Effects of Integrative Health and Medicine Modalities Among Outpatients With Moderate-To-Severe Symptoms
Authors: Rodgers-Melnick Samuel N. , Srinivasan Roshini , Rivard Rachael L. , Adan Francoise , Dusek Jeffery A. 
Published: May 2024

Background Patients seeking integrative health and medicine (IHM) modalities often present with multiple physical and psychological concerns. Research supports IHM’s effectiveness for addressing symptoms over longer time periods. However, few studies have evaluated immediate outpatient effects. Objective This study describes pre-encounter patient-reported outcome (PRO) clusters and examines the immediate clinical effectiveness of IHM modalities on pain, stress, and anxiety among outpatients with moderate-to-severe symptoms. Methods A retrospective review was conducted of encounters among adults presenting to outpatient acupuncture, chiropractic, massage, integrative medicine consultation, or osteopathic manipulation treatment between January 2019 and July 2020. Encounters were included if patients reported pre-encounter pain, stress, or anxiety ≥4 on a numeric rating scale (NRS). Outcome analyses included random effects for patient and provider using a mixed model. Results Across 7335 clinical encounters among 2530 unique patients (mean age: 49.14 years; 81.0% female; 75.9% White; 15.8% Black/African American), the most common pre-encounter PRO clusters were pain, stress, and anxiety ≥4 (32.4%); pain ≥4 only (31.3%); and stress and anxiety ≥4 (15.6%). Clinically meaningful single-encounter mean [95% CI] changes were observed across all modalities in pain (−2.50 [-2.83, −2.17]), stress (−3.22 [-3.62, −2.82]), and anxiety (−3.05 [-3.37, −2.73]). Conclusion Patients presenting to outpatient IHM with moderate-to-severe symptoms most often presented with pain, stress, and anxiety ≥4 on the NRS. Multiple IHM modalities yielded clinically meaningful (≥2 unit) immediate reductions in these symptoms. Future research measuring immediate and longitudinal effectiveness is needed to optimize the triage and coordination of IHM modalities to meet patients’ needs.
Elevating fetal hemoglobin: recently discovered regulators and mechanisms
Authors: Khandros Eugene , Blobel Gerd A. 
Published: May 2024

Abstract
It has been known for over half a century that throughout ontogeny, humans produce different forms of hemoglobin, a tetramer of α- and β-like hemoglobin chains. The switch from fetal to adult hemoglobin occurs around the time of birth when erythropoiesis shifts from the fetal liver to the bone marrow. Naturally, diseases caused by defective adult β-globin genes, such as sickle cell disease and β-thalassemia, manifest themselves as the production of fetal hemoglobin fades. Reversal of this developmental switch has been a major goal to treat these diseases and has been a driving force to understand its underlying molecular biology. Several review articles have illustrated the long and at times arduous paths that led to the discovery of the first transcriptional regulators involved in this process. Here, we survey recent developments spurred by the discovery of CRISPR tools that enabled for the first time high-throughput genetic screens for new molecules that impact the fetal-to-adult hemoglobin switch. Numerous opportunities for therapeutic intervention have thus come to light, offering hope for effective pharmacologic intervention for patients for whom gene therapy is out of reach.
Iron, hemochromatosis genotypes, and risk of infections: a cohort study of 142 188 general population individuals
Authors: Mottelson Mathis , Glenthøj Andreas , Nordestgaard Børge Grønne , Ellervik Christina , Petersen Jesper , Bojesen Stig Egil , Helby Jens 
Published: May 2024

Abstract
It is unclear whether risk of infection is increased in individuals with hereditary hemochromatosis and in individuals with low or high plasma iron, transferrin saturation, or ferritin. Therefore, we tested whether high and low iron, transferrin saturation, and ferritin are associated with risk of infections observationally and genetically through HFE genotypes. We studied 142 188 Danish general population individuals. Iron, transferrin saturation, and ferritin were measured in 136 656, 136 599, and 38 020 individuals, respectively. HFE was genotyped for C282Y and H63D in 132 542 individuals. Median follow-up after study enrollment was 8 years (range, 0-38) for hospital and emergency room admissions with infections (n = 20 394) using the National Patient Register, covering all Danish hospitals. Hazard ratios for any infection were 1.20 (95% confidence interval [CI], 1.12-1.28) and 1.14 (95% CI, 1.07-1.22) in individuals with plasma iron ≤5th or ≥95th percentile compared with individuals with iron from 26th to 74th percentiles. Findings for transferrin saturation were similar, whereas infection risk was not increased in individuals with ferritin ≤5th or ≥95th percentile. Hazard ratios in C282Y homozygotes vs noncarriers were 1.40 (95% CI, 1.16-1.68) for any infection, 1.69 (95% CI, 1.05-2.73) for sepsis, and 2.34 (95% CI, 1.41-3.90) for death from infectious disease. Risk of infection was increased in C282Y homozygotes with normal plasma iron, transferrin saturation, or ferritin, and in C282Y homozygotes without liver disease, diabetes, and/or heart failure. In summary, low and high plasma iron and transferrin saturation were independently associated with increased infection risk. C282Y homozygotes had increased risk of any infection, sepsis, and death from infections. Even C282Y homozygotes with normal iron, transferrin saturation, or ferritin, not currently recommended for genotyping, had increased infection risk.
Does IPSS-R downstaging before transplantation improve the prognosis of patients with myelodysplastic neoplasms?
Authors: Scheid Christof , Eikema Diderik-Jan , van Gelder Michel , Salmenniemi Urpu , Maertens Johan , Passweg Jakob , Blaise Didier , Byrne Jennifer L. , Kröger Nicolaus , Sockel Katja , Chevallier Patrice , Bourhis Jean Henri , Cornelissen Jan J. , Sengeloev Henrik , Finke Jürgen , Snowden John A. , Gedde-Dahl Tobias , Cornillon Jérôme , Schanz Urs , Patel Amit , Koster Linda , de Wreede Liesbeth C. , Hayden Patrick , Raj Kavita , Drozd-Sokolowska Joanna , Gurnari Carmelo , Onida Francesco , McLornan Donal P. , Robin Marie , Yakoub-Agha Ibrahim 
Published: May 2024

Abstract
In patients with myelodysplastic syndrome (MDS), higher revised International Prognostic Scoring System (IPSS-R) scores at transplant are associated with worse transplant outcome and, thus, lowering IPSS-R scores by therapeutic intervention before transplantation may seem beneficial. However, there is no evidence, to date, to support this approach. In a retrospective analysis, a total of 1482 patients with MDS with sufficient data to calculate IPSS-R score at diagnosis and at time of transplantation were selected from the European Society for Blood and Marrow Transplantation transplant registry and analyzed for transplant outcome in a multivariable Cox model including IPSS-R score at diagnosis, treatment intervention, change in IPSS-R score before transplant, and several patient and transplant variables. Transplant outcome was unaffected by IPSS-R score change in untreated patients and moderately superior in patients treated with chemotherapy with improved IPSS-R score at transplant. Improved IPSS-R score after hypomethylating agents (HMAs) or other therapies showed no beneficial effect. However, when IPSS-R score progressed after chemotherapy, HMAs, or other therapies, transplant outcome was worse than without any prior treatment. Similar results were found when reduction or increase in bone marrow (BM) blasts between diagnosis and transplantation was considered. The results show a limited benefit of IPSS-R score downstaging or reduction of BM blasts after chemotherapy and no benefit for HMAs or other treatments and thus question the role of prior therapy in patients with MDS scheduled for transplantation. The model-based survival estimates should help inform decision-making for both doctors and patients.
The biological and clinical impact of deletions before and after large chromosomal gains in multiple myeloma
Authors: Cirrincione Anthony M. , Poos Alexandra M. , Ziccheddu Bachisio , Kaddoura Marcella , Bärtsch Marc-Andrea , Maclachlan Kylee , Chojnacka Monika , Diamond Benjamin , John Lukas , Reichert Philipp , Huhn Stefanie , Blaney Patrick , Gagler Dylan , Rippe Karsten , Zhang Yanming , Dogan Ahmet , Lesokhin Alexander M. , Davies Faith , Goldschmidt Hartmut , Fenk Roland , Weisel Katja C. , Mai Elias K. , Korde Neha , Morgan Gareth J. , Usmani Saad , Landgren Ola , Raab Marc S. , Weinhold Niels , Maura Francesco 
Published: May 2024

Abstract
Acquisition of a hyperdiploid (HY) karyotype or immunoglobulin heavy chain (IgH) translocations are considered key initiating events in multiple myeloma (MM). To explore if other genomic events can precede these events, we analyzed whole-genome sequencing data from 1173 MM samples. By integrating molecular time and structural variants within early chromosomal duplications, we indeed identified pregain deletions in 9.4% of patients with an HY karyotype without IgH translocations, challenging acquisition of an HY karyotype as the earliest somatic event. Remarkably, these deletions affected tumor suppressor genes (TSGs) and/or oncogenes in 2.4% of patients with an HY karyotype without IgH translocations, supporting their role in MM pathogenesis. Furthermore, our study points to postgain deletions as novel driver mechanisms in MM. Using multiomics approaches to investigate their biologic impact, we found associations with poor clinical outcome in newly diagnosed patients and profound effects on both the oncogene and TSG activity despite the diploid gene status. Overall, this study provides novel insights into the temporal dynamics of genomic alterations in MM.
Deciphering the functional role of insular cortex stratification in trigeminal neuropathic pain
Authors: Islam Jaisan , Rahman Md Taufiqur , KC Elina , Park Young Seok 
Published: May 2024

AbstractTrigeminal neuropathic pain (TNP) is a major concern in both dentistry and medicine. The progression from normal to chronic TNP through activation of the insular cortex (IC) is thought to involve several neuroplastic changes in multiple brain regions, resulting in distorted pain perception and associated comorbidities. While the functional changes in the insula are recognized contributors to TNP, the intricate mechanisms underlying the involvement of the insula in TNP processing remain subjects of ongoing investigation. Here, we have overviewed the most recent advancements regarding the functional role of IC in regulating TNP alongside insights into the IC’s connectivity with other brain regions implicated in trigeminal pain pathways. In addition, the review examines diverse modulation strategies that target the different parts of the IC, thereby suggesting novel diagnostic and therapeutic management of chronic TNP in the future.
Single nucleotide polymorphisms in the KRT82 promoter region modulate irregular thickening and patchiness in the dorsal skin of New Zealand rabbits
Authors: Zhao Bohao , Cai Jiawei , Zhang Xiyu , Li Jiali , Bao Zhiyuan , Chen Yang , Wu Xinsheng 
Published: May 2024

Abstract
Background
While rabbits are used as models in skin irritation tests, the presence of irregular patches and thickening on the dorsal skin can affect precise evaluation. In this study, genes associated with patchiness or non-patchiness on the dorsal skin of New Zealand rabbits were investigated to identify potential regulators of the patchiness phenotype.

Results
The results showed that parameters associated with hair follicles (HFs), such as HF density, skin thickness, and HF depth, were augmented in rabbits with the patchiness phenotype relative to the non-patchiness phenotype. A total of 592 differentially expressed genes (DEGs) were identified between the two groups using RNA-sequencing. These included KRT72, KRT82, KRT85, FUT8, SOX9, and WNT5B. The functions of the DEGs were investigated by GO and KEGG enrichment analyses. A candidate gene, KRT82, was selected for further molecular function verification. There was a significant positive correlation between KRT82 expression and HF-related parameters, and KRT82 overexpression and knockdown experiments with rabbit dermal papilla cells (DPCs) showed that it regulated genes related to skin and HF growth and development. Investigation of single nucleotide polymorphisms (SNPs) in the exons and promoter region of KRT82 identified four SNPs in the promoter region but none in the exons. The G.-631G > T, T.-696T > C, G.-770G > T and A.-873 A > C alleles conformed to the Hardy − Weinberg equilibrium, and three identified haplotypes showed linkage disequilibrium. Luciferase reporter assays showed that the core promoter region of KRT82 was located in the − 600 to − 1200 segment, in which the four SNPs were located.

Conclusions
The morphological characteristics of the patchiness phenotype were analyzed in New Zealand rabbits and DEGs associated with this phenotype were identified by RNA-sequencing. The biological functions of the gene KRT82 associated with this phenotype were analyzed, and four SNPs were identified in the promoter region of the gene. These findings suggest that KRT82 may be a potential biomarker for the breeding of experimental New Zealand rabbits.