bluuebunny/crossref_metadata_2025_split huggingface dataset:
The challenge of colorectal cancer (CRC) screening in low and middle-income countries (LMIC): Acceptance, knowledge, and preferences in Brazil.
Authors: Filogonio Victor , Maia Yara Rafaela , Rebelo Matheus Alexandre , Rodrigues Joao Secol , Maia Lucas Henrique 
Published: August 2024

153 Background: Presenting an increasing incidence and high mortality rates, CRC is a challenge that many LMIC face and struggle to establish an effective screening strategy. Brazil is one of the few Latin American countries and LMIC that have a population-based CRC screening program, targeting ages 50-74 and performing a fecal occult blood test (FT) every 2 years and colonoscopy/sigmoidoscopy as a confirmatory test. Methods: We conducted a survey in patients visiting the primary care unit in the months of January and March 2024 in three distinct settings (Rural, Suburban, and Urban) aiming to estimate acceptance, knowledge, and preferences regarding FT and colonoscopy. Patients aged 50-74 were invited to join this study, excluding those with a history of CRC, and we used the integrated digital charting platform to set demographic variables. At the end of the survey, participants were invited to undergo CRC screening. Those who refuse to screen would select the main reason. Results: A total of 1,031 individuals responded the survey, which 52% were females and the median age was 62 years. A total of 763 (74%) accepted to undergo CRC screening with an overall preference for FT (72%) compared to colonoscopy (53,5%). FT acceptance remained somewhat constant in both gender subgroups (70-75%), and a lower colonoscopy acceptance in the male subgroup (46%). In the subdivided geographic setting groups, the rural population (12%) had the lowest knowledge score and the lowest overall acceptance rate (65%), ranking “No symptoms” as the main reason for not screening. The suburban and urban subgroups showed an equivalent overall acceptance rate (74-75%), ranking “Busy schedule” and “Healthy lifestyle” as the main reasons for not screening. Conclusions: Data suggests that an effective CRC screening depends on multiple factors. While literature sustains the weight of cost and long waiting times, this study contributes adding a new, more granular perspective. Efforts in patient education, and clarification of misconceptions and anxieties could prove to be an important step in the right direction. A closer contact between patient and healthcare provider could make the difference between screening or not. A leave of absence or mailed FT might be of great benefit for those with a busy schedule, while interaction with CRC survivors seems to drastically increase colonoscopy acceptance, an important intervention that should be encouraged and widespread. Although this study has its limitations due to sample size and geographic characteristics, it lays down a new layer in understanding the individuals and planning actions to prevent the advance of CRC in LMIC.
COVID-19 infection impact on race and clinical outcome of patients with breast cancer: A nationwide analysis.
Authors: Suenghataiphorn Thanathip , Kulthamrongsri Narathorn , Lohawatcharagul Tuntanut , Kansuttiviwat Chalermkiat , Saowapa Sakditad 
Published: August 2024

16 Background: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in females worldwide. Recent data showed the detrimental effects of COVID-19 infection on other neoplasm conditions, causing increased mortality rates and complications. However, limited information exists on the specific impacts of COVID-19 infection in patients hospitalized for breast cancer, as well as racial impact differences. Methods: We analyzed the 2020 U.S. National Inpatient Sample (NIS) to investigate the effects of COVID-19 infection on cases primarily admitted due to breast cancers. Adjusted odds ratios (aORs) for specified outcomes were calculated through multivariable logistic and linear regression analyses. The primary outcome was inpatient mortality, with secondary outcomes including system-based complications. Statistical significance was established at a p-value of 0.05. Results: We identified 25,559 patients with a primary discharge diagnosis of breast cancer. The mean age was 59.7 years; 99.28% were female. In the non-COVID group, Caucasians accounted for 60%, followed by African Americans (19%). However, in the COVID-19 group, African Americans predominated with 41%, followed by Caucasian (35%) (p-value = 0.05). Of these, 0.52% (85/25,559) had a concurrent diagnosis of COVID-19 infection. In a survey multivariable logistic and linear regression model adjusting for patient and hospital factors, COVID-19 infection was associated with higher in-hospital mortality (aOR 6.07; 95% CI (1.26, 29.13), p = 0.024), higher mean length of stay(b 5.22; 95% CI (2.08,8.36) p =0.001), acute respiratory failure (aOR 4.88; 95% CI (1.51, 15.77), p = 0.008), coagulopathy (aOR 8.38; 95% CI (2.19, 32.02), p=0.002) and SIRS (aOR 6.38; 95% CI (1.25, 32.50), p = 0.026). We observed non-significant, but increased, risks of acute kidney injury (AKI), shock, and sepsis, as well as total hospitalization costs in COVID-19-positive patients. Conclusions: In conclusion, our study underscores that COVID-19 infection is associated with higher in-hospital mortality and other clinical outcomes in breast cancer patients, as well as, a disproportionated impact against some races. Future longitudinal studies are warranted to comprehensively assess the causation of these clinical outcomes in this population.
Voice-based depression assessment in patients with gynecological cancer.
Authors: Higashiyama Nozomi , Yamaguchi Ken , Umemiya Maki , Inayama Yoshihide , Koike Ayami , Ueda Akihiko , Mizuno Rin , Taki Mana , Yamanoi Koji , Murakami Ryusuke , Hamanishi Junzo , Mandai Masaki 
Published: August 2024

161 Background: Although depression in patients with cancer can lead to a deterioration of treatment adherence and quality of life (QOL), diagnosis of depression in patients with cancer is difficult due to symptoms overlapping with side effects of cancer treatment such as fatigue. Traditional screening tools like the PHQ-9 questionnaire are underutilized in clinical practice. Recently, interest has grown in utilizing patients' voices to assess their mental well-being. This study aims to evaluate depression in patients with gynecological cancer and explore the usefulness of voice analysis as a depression detection tool. Methods: PHQ-9 scores were collected from 197 patients with gynecological cancer, with 28 cases undergoing longitudinal assessments at diagnosis, postoperatively, and during chemotherapy. Voice recordings were obtained from 70 patients at diagnosis, alongside serum samples from 22 patients. The PHQ-9 scores were compared across different treatment periods, with a specific focus on patients exhibiting a PHQ score of ≧10, who can be diagnosed with Major Depressive Disorder (MDD). The provision of supportive care for MDD patients was also verified. A random forest model was developed from voice features obtained from 70 patients, with hyperparameter tuning and cross-validation to predict mild depression. Serum metabolites were comprehensively analyzed between depression prediction group and normal prediction group by the depression prediction model. Results: Mean PHQ-9 scores decreased over time since diagnosis; initially 6.50 ± 4.99 (mean ±SD), post-operatively 6.18 ± 4.25, and during chemotherapy 4.88 ± 4.29. The frequencies of MDD also decreased over the clinical course; at diagnosis 24.3%, post-operatively 15.5%, and during chemotherapy 15.4%. Out of 17 cases of MDD during chemotherapy, only one (6.25%) received psychiatric intervention. All MDD cases during chemotherapy had PHQ-9 scores of 5 or higher, representing mild depression at diagnosis. Mild depression at diagnosis could be predicted with an AUC of 0.89 using voice features. Metabolites identified by the voice-based depression prediction model were associated with depression, such as xanthine, methionine, and taurocholic acid. Conclusions: Depression during chemotherapy is often not intervened. Patients with mild depression at diagnosis tend to develop MDD during chemotherapy. Voice-based mental health assessment at diagnosis is possibly a promising screening tool for depression during subsequent cancer treatment. Clinical trial information: UMIN000044266 .
A scalable 3D spatial multi-omics method for high-plex morpho-molecular imaging of millimeter-thick tissues.
Authors: Lai Hei Ming , Chan Shuk Ling 
Published: August 2024

162 Background: Tissues are three-dimensional (3D). However, current histopathology only allows 2D and single-marker tissue views. Methods: We utilized tissue clearing, supramolecular histochemistry, light-sheet microscopy, and image processing algorithms to compile an end-to-end multi-modality pipeline for 3D digital pathology and oncology diagnostics development. Results: Our end-to-end solution allow parallelized, fully automated processing of formalin-fixed or paraffin-embedded tissues of 1cm3 size. With a tissue-to-image time of 6 days, the whole intact tissue block can be non-destructively imaged with our newly developed 3D HnE (Hematoxylin-analogue & Eosin stain) and 4-plex immunohistochemistry (IHC). Deep and homogeneous penetration of staining was achieved such that all stained markers can be quantified as ground truth. The stained and cleared tissue can be recycled for subsequent FFPE 2D histology over multiple cycles for higher-plex imaging, and is also applicable to simultaneous survey of mRNA with multiplexed fluorescent in situ hybridization (FISH), post-translational modifications such as histone modifications via IHC, and glycosylation profiling with lectins. Image analysis readily allows high-dimensional clustering of cells based on their multi-modal biomolecular expression profiles, morphology, spatial locations, and neighborhoods. The method is applicable to a wide variety of human and murine tissues. Conclusions: Our 3D digital pathology platform enables maximal information extracted for precision diagnostics and advanced biomedical research.
New approaches to active monitoring: Patient-reported outcomes and wearables utilisation in Waldenstrom macroglobulinemia.
Authors: Summers Kim , Agrippa Orlando , D'Sa Shirley 
Published: August 2024

168 Background: Waldenstrom macroglobulinemia (WM) is a rare haematological malignancy that has seen an emergence of novel targeted therapies. With a range of clinical features impacting quality of life (QoL), there is a need for disease-specific patient-reported outcomes (PRO), outside of existing measures with limited validity in WM. The aim of this work was to enrich understanding of the patient experience and identify potential WM-specific metrics, through wearable-captured physiological metrics and electronic-PROs (ePROs). Methods: Informed consent was provided by 79 patients with WM for the analysis of data from an FDA-cleared wearable smartwatch capturing activity, sleep, and heart rate, and a mobile app for patients to input daily ePROs. These ePROs included treatments taken, EQ-5D-5L, and disease symptoms (fatigue, weakness, numbness/tingling, breathlessness, difficulty concentrating/confusion, vision, rash, night sweats, dizziness/light-headedness, constipation, loss of appetite, diarrhoea, and vomiting). Data was integrated within a digital platform, and anonymised extracts analysed as a cohort and by treatment. Results: Patients had a mean±SD (range) age of 65±10 (43-88) years. 53% were female. As of the most recent self-reported treatment entry, 22% (17/79) reported Bruton tyrosine kinase inhibitor (BTKi) use. Completion rates over a 142-day snapshot for daily PROs was 60%, and 85% across wearable activity and sleep metrics (devices synced=58/79). A cohort mean EQ-5D-5L Score of 0.760±0.181 and Health State (0-100) of 74±18 was reported. The highest symptom severity scores (1-5) were ‘fatigue’ (1.9/5), ‘weakness’ (1.7/5), and ‘numbness/tingling’ (1.5/5), all other symptoms reporting a mean score of 1.4 or less. Increasing activity levels significantly correlated with decreasing symptom severity and increasing QoL scores (p<0.05). Lower symptom severity also correlated with higher total sleep durations, contrasting higher ‘difficulty concentrating/confusion’, ‘dizziness/light-headedness’, and ‘usual activity impairment’ scores with increasing levels of deep sleep. Breathing disturbance intensities (36.8 vs. 17.6, p=0.008) and nightly wakeup counts (1.9 vs. 1.6, p=0.038), tracked by wearables, were significantly higher in patients reporting BTKi treatment compared to the remaining cohort. Conclusions: Our data support the enrichment of knowledge around baseline physiological and QoL metrics for patients with WM, demonstrating the feasibility of a digital ecosystem of wearable-captured and ePRO metrics at a high data completeness level. Further work will ensure the generation of more population-representative outputs, through the expansion of the patient cohort, and a greater depth of insight into the impact of health events, disease complications, and therapeutic intervention on these remotely-tracked metrics.
Outcome analysis of autologous stem cell transplantation in refractory and relapsed Hodgkin lymphoma: Insights from a North African single-institution study.
Authors: Maaroufi Marouane , Douma Soukaina , Rachid Mohamed , Aajafir Ilias 
Published: August 2024

172 Background: The standard therapy for primary refractory or relapsed Hodgkin lymphoma (HL) involves the administration of high-dose chemotherapy followed by autologous stem cell transplantation (HDC/ASCT). Nevertheless, several risk factors may influence survival outcomes. We assessed outcomes of patients in this setting who underwent HDC/ASCT by performing survival analysis and studying prognostic factors affecting survival. Methods: We conducted a single-institution retrospective analysis of patients with relapsed/refractory HL who received HDC/ASCT between January 2018 and December 2022. Patients’ status evaluation before ASCT was performed by Fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) Scan and Computed Tomography (CT) Scan. The used conditioning regimen was BEAM (Carmustine, Etoposide, Cytarabine, and Melphalan). The primary endpoints were progression-free survival (PFS) and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method, and survival differences between groups were assessed using the Log-Rank test. Results: Thirty-five patients diagnosed with relapsed/refractory HL were included in the study. Among them, 26 patients (74%) had refractory disease, while 9 patients (26%) relapsed following completion of first-line chemotherapy. All patients were treated with HDC/ASCT. Prior to ASCT, 30 patients underwent assessment using FDG-PET Scan, while CT Scan was employed for evaluation in 5 patients. Twenty-three patients (66%) were in complete remission, 8 patients (23%) were in partial remission, and 4 patients (11%) had progressive disease. With a median follow-up of 24.36 months after transplantation, 28 patients (80%) were in remission, 6 patients (17%) had disease progression, and one patients died of septic shock. The 2-year PFS and OS rates for the total population were 85.4% and 97.1%, respectively. Response to first-line chemotherapy did not have a substantial impact on prognosis, as evidenced by a 2-year PFS rate of 76.2% vs. 88.9% (p=0.88) and a 2-year OS rate of 100% vs. 96.2% (p=0.56) for patients with relapsed and refractory disease, respectively. The 2-year PFS and OS rates for patients receiving autograft during complete remission, partial response, and tumor progression were 93.8% vs. 87.5% vs. 50% (p=0.005), respectively; and 95.7% vs. 100% vs. 100%, respectively (p=0.77). Patients who had negative pre-transplant PET-Scans demonstrated a 2-year PFS rate of 92.9% vs. 64.8% for those with positive PET-scans (p=0.004). Conclusions: The findings of our study affirm the established practice of HDC/ASCT for individuals facing relapsed/refractory HL. The disease status at transplant and the pre-transplant PET-Scan status prove to be crucial factors in predicting patients’ outcomes, while response to first-line chemotherapy did not influence prognosis.
Molecular basis for JAK2 inhibition with type II compounds.
Authors: Jacome Dafne , Miao Ya , Haikarainen Teemu 
Published: August 2024

176 Background: Upon prolonged exposure, the therapeutic efficiency of current clinical JAK2 inhibitors (type I inhibitors) can be attenuated, leading to drug resistance both in vitro and in vivo through non-genetic mechanisms. In contrast, type II inhibitors stabilize the inactive conformation of the kinase domain preventing the heterodimerization-mediated JAK2 activation. This confers efficacy to type I inhibitor persistent cells, improved efficacy against myeloproliferative neoplasms and other cancers such as B-cell acute lymphoblastic leukemia. Despite the advantages of type II JAK inhibitors, the discovery of type II inhibitor resistance mutation, L884P, in the kinase domain has hampered the further development of JAK2-targeted type II therapeutics. Methods: Here we use combination of protein-inhibitor binding assays, cell-based assays, X-ray crystallography, and computational tools to elucidate the resistance mechanism of JAK2-L884P mutation, to facilitate the development of type II inhibitors with activity against both wild-type and L884P mutated JAK2. Results: We have determined an atomic resolution crystal structure of JAK2-L884P mutant, revealing that mutation induces local changes in the structure but not in the ATP pocket. Furthermore, we have identified several type II compounds inhibiting. Interestingly, they show no major differences in potency in vitro against wild-type of L884P mutated JAK2. Selected compounds profiled in cell lines carrying wild-type or L884P-mutated JAK2, show differences in their cell viability, indicating that a resistance arises via allosteric effects. Conclusions: L884P mutation impacts the inhibitory potency of type II inhibitors via allosteric mechanism.Crystallographic analysis of our type II shortlisted compounds revealed that they differ in their binding modes and suggests that L884P-insensitive drugs can be developed. Preliminary cell-based experiments results confirm these findings. We will now focus on validating these observations with biomolecular simulations to clarify the molecular basis for the inhibitor resistance via L884P mutation. Our studies will facilitate the development of novel type II drugs against JAK2 in myeloproliferative neoplasms.
Integrating lifestyle medicine into cancer care: A new paradigm.
Authors: Hundal Jasmin , Sirotin Nicole 
Published: August 2024

179 Background: Amid rising global cancer rates and obesity-related cancer risks, oncology must blend traditional cancer treatments with evidence-based lifestyle medicine (LM) to enhance patient outcomes. LM—evidence-based interventions in nutrition, exercise, sleep, avoiding substances, and social connection —emerges as a critical tool in the care spectrum. ASCO and ACS guidelines incorporating lifestyle interventions are limited, and existing ones have notable implementation gaps. This study advocates for integration of LM into cancer care. Such interventions, supported by growing research, offer significant promise in reducing cancer treatment side effects and improving outcomes, highlighting an urgent need for their incorporation into oncological protocols. Methods: The Department of Preventive Medicine at Cleveland Clinic Abu Dhabi (CCAD) launched an LM program at the Oncology Institute. Oncologists refer to LM physicians who assess patients using an LM-validated questionnaire. Cardiometabolic risk factors: body composition, waist circumference, lipid profile, hemoglobin A1c, high-sensitivity CRP, liver function, and liver elastography are tested at baseline and 3 months. Patients receive personalized LM treatment by certified physicians, dieticians, physiatrists, and psychologists, aimed at reducing treatment side effects and enhancing cancer outcomes while improving cardiometabolic health. Follow-ups at 6 weeks and 3 months post-intervention ensure progress tracking and reassessment. Results: Initiated in January 2021, it began as a pilot program for breast cancer patients and has since expanded to all cancer patients. To date, it enrolled 425 patients, evidencing sustainability and acceptance within the patient community. Referral rates from oncologists have shown a steady increase, reflecting the program's growing credibility and utility. Patient satisfaction levels are reported to be high. Preliminary outcomes indicate improvements in both physical and psychological health metrics, suggestive of the program's comprehensive impact. Conclusions: The pioneering oncology LM program at CCAD established a transformative model that seamlessly integrates LM into traditional oncology care and acts as a bridge to survivorship. By ensuring sustained access to lifestyle interventions from the point of diagnosis through post-treatment, the program aligns with the latest research and ASCO/ACS guidelines, pioneering a new standard in cancer treatment. It can effectively address cardiometabolic risks, including obesity, and reduce treatment-related adverse outcomes. This program demonstrates the feasibility and a replicable global model, one that merges evidence-based lifestyle practices with standard oncological care to create a unified approach that could be adopted by healthcare systems worldwide, marking a significant step in the evolution of patient-centered cancer care.