bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unlocking the Next Frontier in Precision Oncology: Addressing Drug-Tolerant Residual Disease
Authors: Lin Jessica J. , Gainor Justin F. , Lam Vincent K. , Lovly Christine M. 
Published: June 2024

Summary:
Drug-tolerant residual disease (DTRD) after the initial maximal response to a systemic therapy can serve as a tumor reservoir for the development of acquired drug resistance and represents a major clinical challenge across various cancers and types of therapies. To unlock the next frontier in precision oncology, we propose a fundamental paradigm shift in the treatment of metastatic cancers with a sharpened focus towards defining, monitoring, and therapeutically targeting the DTRD state.
Clinical Validation of a Cell-Free DNA Fragmentome Assay for Augmentation of Lung Cancer Early Detection
Authors: Mazzone Peter J. , Bach Peter B. , Carey Jacob , Schonewolf Caitlin A. , Bognar Katalin , Ahluwalia Manmeet S. , Cruz-Correa Marcia , Gierada David , Kotagiri Sonali , Lloyd Kathryn , Maldonado Fabien , Ortendahl Jesse D. , Sequist Lecia V. , Silvestri Gerard A. , Tanner Nichole , Thompson Jeffrey C. , Vachani Anil , Wong Kwok-Kin , Zaidi Ali H. , Catallini Joseph , Gershman Ariel , Lumbard Keith , Millberg Laurel K. , Nawrocki Jeff , Portwood Carter , Rangnekar Aakanksha , Sheridan Carolina Campos , Trivedi Niti , Wu Tony , Zong Yuhua , Cotton Lindsey , Ryan Allison , Cisar Christopher , Leal Alessandro , Dracopoli Nicholas , Scharpf Robert B. , Velculescu Victor E. , Pike Luke R. G. 
Published: June 2024

Abstract
Lung cancer screening via annual low-dose computed tomography has poor adoption. We conducted a prospective case–control study among 958 individuals eligible for lung cancer screening to develop a blood-based lung cancer detection test that when positive is followed by a low-dose computed tomography. Changes in genome-wide cell-free DNA fragmentation profiles (fragmentomes) in peripheral blood reflected genomic and chromatin characteristics of lung cancer. We applied machine learning to fragmentome features to identify individuals who were more or less likely to have lung cancer. We trained the classifier using 576 cases and controls from study samples and validated it in a held-out group of 382 cases and controls. The validation demonstrated high sensitivity for lung cancer and consistency across demographic groups and comorbid conditions. Applying test performance to the screening eligible population in a 5-year model with modest utilization assumptions suggested the potential to prevent thousands of lung cancer deaths.
Significance: Lung cancer screening has poor adoption. Our study describes the development and validation of a novel blood-based lung cancer screening test utilizing a highly affordable, low-coverage genome-wide sequencing platform to analyze cell-free DNA fragmentation patterns. The test could improve lung cancer screening rates leading to substantial public health benefits.
See related commentary by Haber and Skates, p. 2025
BIOLOGICALLY ACTIVE COPMOUNDS IN THE EXRTACTS OF SPERANSKIA TUBERCULATA (BUNGE) BAILL AND THEIR EFFECT ON THE VIABILITY OF CANCER CELLS OF FIVE DIFFERENT LINES
Authors: Sun Zeyuan , Derkach T. M. 
Published: June 2024

The aim of the work. Identifying the most considerable bioactive compounds in Speranskia tuberculata extracts and studying their effect on the viability of cancer cells of five lines.
Materials and Methods. The herb Speranskia tuberculata extract was prepared based on ethyl acetate and petroleum ether in the 12.5-75 μg/ml concentration range. The presence of compounds in the extracts was investigated by the tandem high-performance liquid chromatography-mass spectroscopy (HPLC/MS) method. The MTT cytotoxicity test was used to evaluate the effectiveness of extracts on five commercially available cell lines: A549 (human lung adenocarcinoma), HEPG2 (human hepatocellular carcinoma of the liver), A375 (human malignant melanoma), HELA (human pancreatic carcinoma), RAW264.7 (macrophage-like cell line from mice transformed with Abelson's leukaemia virus).
Results and Discussion. The peaks of about 300 compounds were identified in the mass spectra. Fifty-six compounds with the largest peaks were investigated from the point of view of manifestations of anticancer, antitumour, antioxidant and anti-inflammatory activity known from the literature. Only 35 of the 56 peaks have a documented effect on the listed diseases, another 15 compounds are active on other diseases, and 6 showed no activity. Of the 35 compounds belonging to 10 chemical classes, alkaloids, lipids, and polyphenols dominate (20 out of 35). Chemical reactions for phytochemical screening of chemical classes found in extracts are presented. In MTT tests, the viability during treatment of 4 out of 5 cell lines significantly decreases with increasing concentration of extracts. Only RAW264.7 cells were stable - their viability did not fall below 75-85%. Ethyl acetate extracts were the most effective. They maximally reduce viability to 18%, and the IC50 of this extract for all cell lines varied between 49-53 μg/ml. For petroleum ether, the IC50 of three lines was 65-74 μg/ml (for A375, the approximate value reached 114 μg/ml).
Conclusions. The peaks of about 300 compounds found in extracts of the herb Speranskia tuberculata were identified by the HPLC/MS. Among the 56 most intense peaks, 35 compounds, according to the literature, have anticancer, antitumour, antioxidant and anti-inflammatory effects. MTT tests showed that the studied extracts significantly reduced the viability of cancer cells in 4 out of 5 lines. IC50 for ethyl acetate extracts is 49-53 μg/ml, and for petroleum ether - 65-74 μg/ml.
ВМІСТ ВІТАМІНУ D У СИРОВАТКАХ КРОВІ МЕШКАНЦІВ ТЕРНОПІЛЬЩИНИ, ХВОРИХ НА ЛАЙМ-БОРЕЛІОЗ І ХРОНІЧНУ ЕПШТЕЙНА – БАРР ВІРУСНУ ІНФЕКЦІЮ
Authors: Юзьків Т. І. , Шкільна М. І. , Івахів О. Л. , Гук М. Т. , Кліщ І. М. 
Published: June 2024

Вступ. Науковці припускають, що вітамін D, завдяки імуномодулювальним властивостям, здатний контролювати противірусну імунну відповідь. Тому необхідно з’ясувати його менеджмент у пацієнтів з вірусними та бактерійними мікст-інфекціями.
Мета дослідження – визначити вміст 25-гідроксивітаміну (25(OH)D) у сироватках крові мешканців Тернопільщини, хворих на Лайм-бореліоз (ЛБ) і хронічну Епштейна – Барр вірусну інфекцію (ЕБВІ) окремо та при їх поєднанні.
Методи дослідження. Обстежено 81 пацієнта з клінічними проявами ЛБ та EБВІ. Діагноз ЛБ встановлювали клінічно, підтверджували серологічно у два етапи (імуноферментний аналіз та імуноблот). Хронічну EБВІ діагностували за допомогою непрямої імунофлуоресценції (технологія БІОЧИП). Активну фазу недуги визначали за високим вмістом ДНК вірусу в полімеразній ланцюговій реакції одночасно у крові та слині хворих. Рівень 25(OH)D визначали шляхом проведення хемілюмінесцентного імуноаналізу. Результати інтерпретували згідно з рекомендаціями Першого українського консенсусу щодо менеджменту вітаміну D (2023): <20 нг/мл – дефіцит вітаміну D (ДВД); ≥20–29 нг/мл – недостатність вітаміну D (НВД); >30–50 нг/мл – достатній рівень вітаміну D (ДРВД); >50–60 нг/мл – безпечний, але не цільовий рівень ­вітаміну D (БРВД); >60–100 нг/мл – зона невизначеності з потенційними перевагами чи ризиками; >100 нг/мл ‒ надлишок/зона токсичності вітаміну D.
Результати й обговорення. Разом ДВД та НВД частіше реєстрували у хворих на хронічну ЕБВІ в активній фазі, поєднану з ЛБ, і тільки на цю недугу порівняно з пацієнтами лише з ЕБВІ в латентній фазі (p<0,05). Разом ДРВД і БРВД переважали у пацієнтів тільки з хронічною ЕБВІ в латентній фазі чи в поєднанні її з ЛБ порівняно з хворими на ЕБВІ в активній фазі разом із ЛБ або окремо (p<0,05). Середній рівень 25(OH)D вищий у пацієнтів із хронічною ЕБВІ в латентній фазі, ніж в осіб з активною фазою недуги як разом із ЛБ, так і без нього (p<0,05), і більший у хворих на хронічну ЕБВІ в латентній фазі в поєднанні з ЛБ порівняно з особами лише з активною фазою ЕБВІ (p<0,05).
Висновки. Визначення вмісту вітаміну D у мешканців Тернопільщини, хворих на ЛБ і хронічну ЕБВІ, за рівнем 25(OH)D проведено вперше, воно дозволило встановити суттєву різницю його вмісту в осіб як лише з ЕБВІ в активній чи латентній фазі, так і в поєднанні з ЛБ.
Event-related Potential Measures of Visual Word Processing in Monolingual and Bilingual Children and Adults: A Focus on Word Frequency Effects
Authors: McArthur Alexander W. D. , Whitford Veronica , Joanisse Marc F. 
Published: June 2024

Abstract
How does language background influence the neural correlates of visual word recognition in children? To address this question, we used an ERP lexical decision task to examine first-language (L1) and second-language (L2) visual word processing in monolingual and bilingual school-aged children and young adults (n = 123). In particular, we focused on the effects of word frequency (an index of lexical accessibility) on RTs and the N400 ERP component. Behaviorally, we found larger L1 versus L2 word frequency effects among bilingual children, driven by faster and more accurate responses to higher-frequency words (no other language or age group differences were observed). Neurophysiologically, we found larger L1 word frequency effects in bilinguals versus monolinguals (across both age groups), reflected in more negative ERP amplitudes to lower-frequency words. However, the bilingual groups processed L1 and L2 words similarly, despite lower levels of subjective and objective L2 proficiency. Taken together, our findings suggest that divided L1 experience (but not L2 experience) influences the neural correlates of visual word recognition across childhood and adulthood.
Near- and Superinertial Internal Wave Responses and the Associated Energy Transfer after the Passage of Tropical Cyclone Fitow at a Midlatitude Shelf Slope
Authors: Yang Wei , Wei Hao , Zhao Liang 
Published: June 2024

Abstract
Observations from a mooring station at the East China Sea (ECS) shelf slope revealed both near- and superinertial dynamic responses to tropical cyclone (TC) Fitow. Different from the typical near-inertial response, near-inertial internal waves (NIWs) after TC Fitow showed a complicated phase pattern due to its superposition with parametric subharmonic instability (PSI)-generated M1 subharmonic waves. The wind-injected near-inertial kinetic energy (NIKE) was largely restrained to the upper 250 m. Wave packet analysis revealed the co-occurrence of enhanced NIKE, circularly polarized near-inertial currents, veering NIW propagation direction, and shrinking NIW vertical wavenumber at the base of the Kuroshio (∼180 m). This indicated the trapping and stalling of the TC-generated NIWs. Intense high-frequency internal waves (HFIWs) appeared immediately after TC Fitow which had an average period of ∼24 min and lasted ∼8 h. HFIWs also existed before the arrival of TC Fitow with a regular semidiurnal cycle. However, the HFIW after TC did not follow the semidiurnal cycle and had much larger amplitudes and longer-lasting periods. Local generation of supercritical flow over a slope or evolution from propagating internal tide as modified by TC may have induced these HFIWs. Along with the occurrence of intense HFIWs after TC Fitow, intense energy transfers from NIWs to HFIWs were identified. Due to the limited vertical propagation of TC-induced NIWs, it was the PSI-generated M1 subharmonic wave rather than the wind-induced NIW that contributed most to the energy transfer.

Significance Statement
Winds blowing over the ocean generate not only surface waves but also another type, so-called internal waves, which can travel down into the ocean. These internal waves carry a large amount of wind-injected energy into the ocean interior and are thought to play an important role in sustaining ocean turbulent mixing and circulation. We provided evidence that the passage of a tropical cyclone (TC) can induce different types of internal wave responses: near-inertial and high-frequency internal waves. Interactions and energy transfer between different internal waves occurred. With the TC-induced near-inertial internal waves trapped in the upper ocean, the background M1 subharmonic waves contributed most to the interactions with high-frequency internal waves. This fact is crucial in understanding the propagation and dissipation of wind-injected energy in the ocean, which plays an important role in controlling the ocean interior mixing and large-scale circulation.
Atrial fibrillation inpatient management patterns and clinical outcomes during the conflict in Syria: An observational cohort study
Authors: Antoun Ibrahim , Aljabal Majed , Alkhayer Alkassem , Mahfoud Yaman , Alkhayer Alamer , Simon Peter , Kotb Ahmed , Barker Joseph , Mavilakandy Akash , Naseer Muhammad Usman , Somani Riyaz , Ng G André , Zakkar Mustafa 
Published: June 2024

Background Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there is no data on AF inpatient management strategies and clinical outcomes in Syria. Objectives The study aims were to review the inpatient management of patients with AF and assess cardiovascular (CV) mortality in a tertiary cardiology centre in Latakia, Syria. Methods A single-centre retrospective observational cohort study was conducted at Tishreen’s University Hospital, Latakia, Syria, from June 2021 to June 2023. Patients ≥16 years of age presenting and being treated for AF as the primary diagnosis with or without a thromboembolic event were included. Medical records were examined for patients’ demographics, laboratory results, treatment plans and inpatient details. Studied outcomes include inpatient all-cause and CV mortality, ischemic and bleeding events, and conversion to sinus rhythm (SR). Results The study included 596 patients. The median age was 58, and 61% were males. 121 patients (20.3%) were known to have AF. A rhythm control strategy was pursued in 39% of patients. Ischemic and bleeding events occurred in 62 (11%) and 12 (2%), respectively. CV and all-cause mortality occurred in 28 (4.7%) and 31 patients (5%), respectively. The presence of valvular heart disease (VHD) (adjusted odds ratio (aOR) = 9.1, 95% confidence interval (CI): 1.7 to 55.1, p < .001), thyroid disease (aOR: 9.7, 95% CI = 1.2 to 91.6, p < .001) and chronic obstructive pulmonary disease (COPD) (aOR: 82, 95% CI: 12.7 to 71, p < .001) were independent risk factors of increased CV inpatient mortality. Conclusion Syrian inpatients admitted with AF in Latakia are relatively younger than those in other countries. Active thyroid disease, COPD and VHD were independent risk factors of inpatient CV mortality with AF.
Clinical predictors of therapeutic failure of occipital nerve stimulation in refractory chronic cluster headache
Authors: Membrilla Javier A , Cuadrado María-Luz , González-García Nuria , Porta-Etessam Jesús , Sánchez-Soblechero Antonio , Lozano Ros Alberto , Gonzalez-Martinez Alicia , Gago-Veiga Ana Beatriz , Quintas Sonia , Rodríguez Vico Jaime S , Jaimes Alex , Llorente Ayuso Lucía , Roa Javier , Estebas Carlos , Díaz-de-Terán Javier 
Published: June 2024

Background Occipital nerve stimulation (ONS) is a treatment with evidence in refractory chronic cluster headache (CCH). However, the variable response rate and cost make it necessary to investigate predictors of response. Methods This is a cross-sectional study conducted through the review of medical records of CCH patients from six hospitals in Madrid. Epidemiological and clinical variables were compared between patients with ONS failure and the rest. ONS failure was defined as the need for device withdrawal or switch off because of lack of response or adverse events. Results From a series of 88 CCH, 26 (29.6%) underwent ONS surgery, of whom 13/26 (50.0%) failed because lack of response. ONS failure group had an earlier headache onset (mean ± SD) of 27.7 ± 6.9 vs. 36.7 ± 11.8 years, p = 0.026) and a higher smoking rate (100% vs. 42.9%, p = 0.006). Stational fluctuations (58.3% vs. 7.7%, p = 0.007) and nocturnal exacerbations (91.7% vs. 53.9%, p = 0.035) were more frequent in the ONS failure group as well. There was no difference between groups in diagnostic delay, years of evolution prior to surgery, mental illness, comorbidity with other headache disorders or chronic pain conditions or prior response to occipital nerves anesthetic blocks. Conclusions Some clinical features such as an early debut, smoking and seasonal or circadian fluctuations could be related to failure of ONS in refractory CCH.
Biomechanical and Histological Study of Retrieved LARS Synthetic Ligaments
Authors: Blakeney William G. , Hayes Alex , Kop Alan , Parry Jeremy , Walsh Michael , Annear Peter , Pabbruwe Moreica 
Published: June 2024

Background: Synthetic grafts have been used for a number of years in anterior cruciate ligament (ACL) reconstruction surgery. One of the more recent additions to the stable of synthetic ligaments is the Ligament Augmentation and Reconstruction System (LARS) ligament. Purpose: To analyze the biomechanics and histology of LARS grafts retrieved due to failure of the device. Study Design: Descriptive laboratory study. Methods: A total of 22 LARS ligament grafts that were explanted from patients were sent for analysis. Five new, unused samples of the standard LARS ACL graft were also analyzed. Biomechanical testing was performed: ultimate tensile force, force versus displacement, and stress versus strain were recorded. Histopathological examination was performed looking for degree of fibrous tissue ingrowth as well as the presence of a foreign body reaction. Results: Of the 22 grafts retrieved, 14 were used for ACL grafts, 1 for a lateral collateral ligament graft, 2 for medial collateral ligament grafts, 4 for gluteal tendon augmentation, and 1 for a supraspinatus augmentation. A severe foreign body reaction was found in 86% of the grafts (18/22) and a mild foreign body reaction in the remaining 14% (4/22). Tissue ingrowth was minimal in the majority of ACL grafts; the other grafts showed moderate tissue ingrowth. Maximal tensile force was significantly higher for the new ACL grafts (mean ± SD, 1667 ± 845 N) compared with the retrieved grafts (897 ± 395 N; P < .05). Conclusion: This study demonstrated that the vast majority of retrieved LARS artificial ligaments had a florid foreign body reaction. There was minimal tissue ingrowth in ACL grafts and moderate ingrowth in other grafts. Retrieved grafts had a decreased ultimate tensile force, which increased their risk of rupture. Clinical Relevance: Surgeons should be cautious in choosing to use these grafts in reconstructive surgery for patients.
Beliefs, Experiences, and Practices of Lady Health Workers in Facilitating Breastfeeding in Rural Communities in Pakistan
Authors: Singletary Nicola , Waqar Farooqi Zoha 
Published: June 2024

Pakistan has extremely poor breastfeeding indicators: fewer than half of infants under 6 months are exclusively breastfed, only 20% of infants are breastfed within the first hour of life, and nearly half are never fed colostrum. The country’s high infant morbidity and mortality is in part due to this suboptimal infant feeding. A network of lady health workers (LHWs) employed by the government facilitate maternal and child health programs, including breastfeeding support in their communities. This study describes LHWs’ perspectives and experiences regarding breastfeeding. We conducted semi-structured interviews with 14 LHWs and used thematic qualitative analysis to code and analyze the data. Our research revealed that LHWs use their role as members of the community and involve influential members of the family to build trust. Frequent home visits beginning prenatally help them address misconceptions about infant feeding. While they have strong knowledge about the benefits of breastfeeding and the importance of colostrum, they demonstrate gaps in their knowledge regarding breast conditions, the safe preparation of human milk substitutes, the physiology of milk production, and supporting mothers who are separated from their baby. Future training should address these areas where LHWs lack knowledge to help mothers facilitate early and exclusive breastfeeding. With adequate training, LHWs are uniquely positioned to use their role as trusted members of the community to effectively counsel families on the importance of breastfeeding and support the clinical needs of women during the perinatal time.
Dangerous Variation or Patient-Centered Care? Palliative Care and Pain Providers’ Comfort, Experiences, and Approaches when Treating Cancer Pain With Coexisting Aberrant Behaviors
Authors: Hadler Rachel A. , Klinedinst Rachel , Jones Christopher A. , Bao Yuhua , Pathak Ravi , Zarrabi Ali J. , Rosa William E. 
Published: June 2024

Background Patients with cancer-related pain are at high risk for aberrant drug use behaviors (ADB), including self-escalation, diversion and concurrent illicit substance or opioid misuse; however, limited evidence is available to guide opioid prescribing for patients with life-limiting illness and concurrent or suspected ADB. We sought to characterize how specialists evaluate for and manage these high-risk behaviors in patients with cancer-related pain. Methods We conducted telephonic semi-structured interviews with palliative care and pain medicine providers. Participants discussed their own comfort and experience level with identifying and managing ADB in patients with life-limiting illness. They were subsequently presented with a series of standardized scenarios and asked to describe their concerns and management strategies. Results 95 interdisciplinary pain and palliative care specialists were contacted; 37 agreed to participate (38.9%). Analysis of interview contents revealed several central themes: (1) widespread discomfort and anxiety regarding safe and compassionate opioid prescribing for high-risk patients, (2) belief that widely used risk-mitigation tools such as opioid contracts and urine drug screens provided inadequate support for decision-making, and (3) lack of institutional and organizational support and guidance for safe prescribing strategies. Most clinicians reported self-education regarding addiction and alternative prescribing/pain management strategies. Providers varied widely in their willingness to discontinue opioid prescribing in a patient with aberrant behavior and pain associated with life-limiting illness. Conclusion Providers caring for patients demonstrating ADB and cancer-related pain struggle to balance safe prescribing with symptom management. Increased guidance is needed regarding opioid prescribing, monitoring, and discontinuation in high-risk patients.
Atherogenic indices in preeclamptic and eclamptic patients in North-Central Nigeria
Authors: Abdulkadir Zainab Ajoke , Ijaiya Munirdeen Aderemi , Adebara Idowu O 
Published: June 2024

Microvascular, placental, haematological and lipid studies suggest striking similarities between preeclampsia/eclampsia and atherosclerosis. Objective To determine the lipid profile and atherogenic indices in preeclamptic/eclamptic patients and compare with normal pregnant women. Methodology Comparative cross-sectional study conducted in North Central Nigeria. The study population was preeclamptic/eclamptic patients and normal pregnant women. A total of 192 women, comprising 96 pregnant women with preeclampsia/eclampsia and an equal number of normotensive controls were recruited consecutively by purposive sampling. Lipid profiles were estimated and atherogenic indices were calculated. Result Coronary heart disease risk ratio (CRR) and atherogenic index of plasma (AIP) showed significantly increased atherogenic potentials in subjects compared to controls. Mean ± SD CRR of subjects was 0.28 ± 0.17, Mean ± SD CRR of controls was 0.44 ± 0.24 ( p = 0.001); Mean ± SD AIP of subjects was 0.32 ± 0.42 and mean ± SD AIP of controls was 0.16 ± 0.26 ( p = 0.003). Conclusion Atherogenic indices show increased atherogenic potentials in preeclamptic/eclamptics.