bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world understanding of the unmet need for treatment of non-covalent BTKi in chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).
Authors: Choksi Rushir J. , Hou Jing-Zhou , Li John , Gart Mike , Vasudevan Anupama , Blanc Simon 
Published: July 2024

e19028 Background: Non-covalent (nc) Bruton Tyrosine Kinase inhibitors (BTKi) for the treatment of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL/SLL) provide patients with a new treatment option after resistance to on-target BTK mutations or PLCγ2 mutations that bypass BTK inhibition. Given the December 1, 2023 accelerated FDA approval for pirtobrutinib, a nc-BTKi, in the treatment of CLL/SLL for treatment of patients who have received at least two prior lines of therapy with a covalent (c) BTKi and a B-Cell Lymphoma 2 Protein Inhibitor (BCL2i), we sought to understand the addressable population for treatment with nc-BTKI therapy in a real-world database of CLL/SLL patients. Methods: We used the Integra Connect PrecisionQ real-world de-identified database of over 3 million cancer pts across 500 sites of care to identify CLL/SLL pts for the analysis. The CLL patients included for the analysis were on a treatment in 2023 and must have had either >5 CLL/SLL diagnosed visits or more CLL/SLL visits than non-CLL/SLL visits if <5 CLL/SLL diagnosed visits. Descriptive analyses were used for this study. Results: Of the 6,992 patients treated for CLL/SLL in 2023, the median age at treatment start was 71, 62% were male, 65% identified as White, 6% as African American, and 29% as Other. Of the pts, 12% received a c-BTKi and BCL2i, 64% received a c-BTKi only, and 12% received a BCL2i only. Of the 12% of pts who received a c-BTKi and BCL2i, 191 pts started a subsequent line of therapy. Among pts who received a c-BTKi and BCL2i, 79% received a BTKi therapy first, 10% received a BCL2i therapy first, and 12% had a line of therapy with both a BTKi and BCL2i. We found 59 pts who received nc-BTKi; among those pts, 51% received a c-BTKi and BCL2i prior to initiation of nc-BTKi. The median age at first treatment for CLL/SLL was 71.7 for those who received a c-BTKi, 71.1 for those who received a BCL2i, and 70.8 for those who received nc-BTKi. The median age at first diagnosis for CLL/SLL was 68 for those who received a c-BTKi, 66 for those who received a BCL2i, and 63 for those who received nc-BTKi. The median time to first treatment was 470 days for pts treated with a c-BTKi, 507 days for pts treated with BCL2i, and 587 days for pts treated with nc-BTKi. Conclusions: We found that among nearly 7,000 treated patients in the database, 12% were treated with both a c-BTKi and BCL2i; of those, just 23% started a subsequent treatment. Among patients who were treated with a nc-BTKi we found their median age at treatment start and diagnosis was lower than those who received a c-BTKi or BCL2i respectively.
Hodgkin’s lymphoma, lymphocyte-depleted, reticular: An NCDB analysis of demographic and socioeconomic factors of diagnosed patients.
Authors: Nowlen Frances , Chin Kat , Jung Huang Po , Halloum Anas , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: July 2024

e19033 Background: Lymphocyte-depleted Hodgkin's lymphoma (LDHL) is an aggressive, rare form of Hodgkin’s lymphoma (HL). The LDHL reticular subtype (LDHL-R) is characterized by a scant invasion of lymphocytes without an increase in collagen fibers by fibroblasts. Patient demographics and clinical features of LDHL-R are poorly understood, causing it to frequently be misdiagnosed as other variants of HL. At diagnosis, patients have often already progressed to late disease staging. The demographic and socioeconomic factors of patients diagnosed with LDHL-R within the National Cancer Database (NCDB) were analyzed to better understand its epidemiology. Methods: A retrospective cohort analysis was performed using data from the 2004-2020 NCDB of the 51 cases of LDHL-R (ICD-O-3 9655). Demographic and socioeconomic factors such as age, sex, race, Hispanic status, treatment facility type, Charles-Deyo score, and 90-day mortality were examined using descriptive statistics. Diagnostic trends were quantified through regression analysis. Results: A total of 51 patients were diagnosed with Hodgkin lymphoma, lymphocyte depletion, reticular subtype within the NCDB. The most common primary site of diagnosis was within lymph nodes of multiple regions (41%). The majority of patients were males (65%), White (72%), and non-Hispanic (74%). Patients tended to have residence in metropolitan counties with populations greater than 1 million (71%) and were enrolled in academic/research programs (36%). Most of the patients were privately insured (41%) followed by those insured by Medicare (29%). A higher percentage of patients were in the top quartile of income earners (31%) than those in the second, third, or fourth quartiles. The incidence rate of diagnosis remained constant from 2004 to 2020 (R² = 0.02). The mean age of diagnosis was 51 years (SD=21, Range=14–90). Using the AJCC System, patients tended to be classified as Stage IV (41%) at diagnosis and had a Charlson-Deyo comorbidity score of 0 (71%). Primary treatment methods involved chemotherapy (84%) and radiation therapy (20%). Surgical intervention was given to 14 patients, and post-surgery survival rates were 93% after 90 days. Conclusions: To the best of our knowledge, this is the first NCDB analysis of the demographic factors of patients diagnosed with LDHL-R. Consistent with previous studies about the aggressiveness of this subtype of Hodgkin’s Lymphoma, most patients received a Stage IV diagnosis. Understanding LDHL-R’s epidemiology could result in significantly earlier diagnoses and improved prognosis. Patients tended to be male, White, and non-Hispanic with a residence in metropolitan counties. To improve understanding of the impact of demographic and socioeconomic factors of the diagnosis, treatment, and survival of patients with LDHL-R, more research is recommended.
Associations of early adverse events with clinical outcomes in patients with NSCLC treated with EGFR tyrosine kinase inhibitors.
Authors: Lin Fang-Ju , Lin Wen-Yen , Wang Chi-Chuan , Shih Jin-Yuan 
Published: July 2024

e20551 Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) constitute the primary treatment modality for EGFR-mutant non-small cell lung cancer (NSCLC). While efficacious, EGFR TKIs are associated with adverse events (AEs) like dermatologic toxicities, diarrhea, and stomatitis. This study examined the prognostic implications of these on-target AEs in NSCLC patients receiving EGFR TKI therapy. Methods: A retrospective cohort study was conducted, encompassing advanced NSCLC patients treated with first-line EGFR TKIs within two distinct healthcare delivery systems in Taiwan between June 2011 and December 2019. Patients were stratified by TKI type, and those who had received AE reliever medications within 180 days prior to EGFR TKI initiation were excluded. We examined correlations between AEs and key endpoints: time to next treatment (TTNT) and overall survival (OS). To minimize immortal time bias, a landmark analysis at 60 days post-treatment initiation was utilized. On-target AEs were identified based on the issuance of at least two prescriptions for AE management on different dates within this period. Multivariable Cox proportional hazards models were utilized to evaluate the association between AEs and clinical endpoints, and a random-effects meta-analysis was performed to combine findings from both institutions. Results: Our analysis included 1,605 patients on gefitinib, 848 on erlotinib, and 1,236 on afatinib. Despite potential variations in AE reporting due to prescribing behaviors, the incidence of AE within the first 60 days of treatment was highest for afatinib, particularly with diarrhea (76.7%) and stomatitis (14.9%), followed by erlotinib with notable skin reactions (49.4%). Gefitinib showed the lowest incidence rates across all examined AEs. Of note, afatinib-treated patients who experienced diarrhea within the initial 60 days demonstrated a statistically significant extension in OS (HR 0.75, 95% CI 0.60-0.92). No significant prognostic link was found for other AEs in afatinib users or any AEs among users of gefitinib and erlotinib. Sensitivity analyses, incorporating modified AE definitions, corroborated these outcomes. Conclusions: Identifying AEs via prescription records for symptom relief poses methodological challenges and introduces uncertainty. Nevertheless, the occurrence of diarrhea within the first 60 days of therapy emerged as a significant predictor of enhanced OS in EGFR-mutant NSCLC patients receiving afatinib. This finding suggests a potential prognostic implication. The correlation was not evident in patients treated with first-line gefitinib or erlotinib.
A comparison of real-world incidence of EGFR exon 20 insertion mutations among patients with NSCLC in five Asian markets, stratified by testing methodology.
Authors: De Richter Pieter , Koo Mei Yee 
Published: July 2024

e20622 Background: Despite the arrival of drugs targeting EGFR exon 20 insertions mutations (ex20ins) in non-small cell lung cancer (NSCLC), testing practices for this specific mutation vary widely between hospitals. In addition, there is a lack of real world data on incidence of ex20ins in different countries in Asia. This study tracks real-world ex20ins incidence by country/region as well as by methodology across 5 different Asian markets. Methods: Ipsos’ Exon 20 Insertion Tracker is an ongoing physician-reported syndicated study. Hospitals in Asia (n = 7 in South Korea; n = 5 in Taiwan; n = 4 in India; n = 5 in Thailand; n = 1 in Hong Kong) were asked to submit data on total number of NSCLC patients tested for EGFR mutations using single marker tests vs multi-gene panel tests, and subsequently asked how many tested positive for ex20ins. Data were collected online on a regular basis from September 2022 in South Korea and Taiwan, from January 2023 in India, and from September 2023 in Thailand and Hong Kong, until December 2023 in all markets. A total of n = 7,657 EGFR-tested patients in South Korea, n = 2,260 in Taiwan, n = 3,970 in India, n = 407 in Thailand and n = 114 in Hong Kong were reported on. Results: Incidence of ex20ins was markedly higher in Hong Kong (3.5%) and Taiwan (3.7%) than in South Korea (1.6%), India (1.4%) and Thailand (1.0%), pointing to a potentially higher incidence in Greater China compared to other parts of Asia. Among this cohort, the use of panel testing for EGFR mutations was highest in India (99%) and lowest in Taiwan (1%). Across the markets, incidence of ex20ins appears to be somewhat higher among those tested with single-marker EGFR tests (2.2%) than those tested with panel-based tests (1.4%), although the opposite was observed in Thailand and Hong Kong. Conclusions: In this large study based on testing results from over 14,400 EGFR-tested patients across 5 different markets in Asia, clear differences in observed incidence of ex20ins mutations were observed, with the incidence in Taiwan being nearly 4 times as high as that in Thailand. This highlights that different testing and biomarker sequencing strategies may be necessary in markets with the highest observed incidence. A secondary finding from this study is that test methodology does appear to have an impact on observed incidence, though this is in part due to very different testing approaches (single-marker vs panel-based) between markets, with the majority of hospitals included in the study in Taiwan preferring a single-marker approach. [Table: see text]
Cold prevention of alopecia during chemotherapy: Real clinical practice.
Authors: Fedorinov Denis , Lyadova Marina , Tuleiko Veronika , Kuzmina Evgenia , Zhuravleva Anastasia , Bikmurzina Olesya 
Published: July 2024

e24132 Background: Alopecia is one of the most common visible adverse effects of anticancer drug therapy. The incidence of grade 2 alopecia can be as high as 90% in patients getting anthracyclines or taxanes. Decreased scalp temperature causes vasoconstriction which limits the flow of chemotherapeutic agents into the scalp and reduces the metabolism of hair follicle cells at the time of maximum concentration of cytotoxic agents in plasma. This leads to a decrease in the antimitotic and antimetabolic effects of chemotherapy. ORBIS II scalp cooling device has been successfully implemented in comprehensive oncology centers. However, the results of large-scale studies are still lacking which delays application of this technology in clinical practice. The aim of our study was to evaluate the efficacy and safety of alopecia cold prophylaxis using ORBIS device in a regional referral center in Russia. Methods: Between 22 June 2022 and 13 December 2023 101 patients (100 women and 1 man) were treated using ORBIS II in the Department of Chemotherapy N1, City Clinical Cancer Hospital N1, Moscow. Various combinations of chemotherapeutic agents depending on cancer type were administered. Breast cancer was the most common type (63), followed by ovarian (15), uterine (9), lung (6) and cervical cancer (3). Other primaries were represented by 1 patient each: pancreatic, rectal, gastric, fallopian tube and colon cancer. Totally 431 scalp cooling procedures were performed including 261 (61%) in breast cancer and 78 (18%) in ovarian cancer patients. Outcomes were evaluated using the CTCAE/CTCAE V5.0 toxicity criteria. We evaluated the development of 1 grade alopecia (hair loss of less than 50% and not requiring a wig) as a positive result. On the contrary, a negative result was registered in patients with grade 2 alopecia, namely hair loss of 50% or more and/or requiring a wig. Results: Grade 1 alopecia was experienced by 61% of patients and the other 39% had grade 2 alopecia. Notably, the highest incidence of grade 2 alopecia was observed in patients who received doxorubicin 60 mg/cm2 + cyclophosphamide 600 mg/cm2 once every 21 days (9.9%). Taxane-based regimens had a 21% incidence of grade 2 alopecia, while platinum-containing regimens had a 11% incidence. No serious adverse events occurred during the application of cold prophylaxis. The procedure was well-tolerated by all patients. Conclusions: The use of a cold helmet is an effective method of preventing chemotherapy-induced alopecia. Our analysis yielded a success rate of 61%, which is comparable to the worldwide data range of 50% to 80%.
Nanosimilars: A Scientific or A Regulatory Debate?
Authors: Demetzos Costas 
Published: July 2024

AbstractThe paper highlights the necessity for a robust regulatory framework for assessing nanomedicines and their off-patent counterparts, termed as nanosimilar, which could be considered as ‘similar’ to the prototype nanomedicine,based on essential criteria describing the ‘similarity’. The term ‘similarity’ should be focused on criteria that describe nanocarriers, encompassing their physicochemical, thermodynamic, morphological, and biological properties, including surface interactions and pharmacokinetics. Nanocarriers can be regarded as advanced self-assembled excipients (ASAEs) due to their complexity and chaotic behavior and should be evaluated by using essential criteria in order for off-patent nanomedicines be termed as nanosimilars, from a regulatory perspective. Collaboration between the pharmaceutical industry, regulatory bodies, and artificial intelligence (AI) startups is pivotal for the precise characterization and approval processes for nanomedicines and nanosimilars and embracing innovative tools and terminology facilitates the development of a sustainable regulatory framework, ensuring safety and efficacy. This crucial shift toward precision R&D practices addresses the complexity inherent in nanocarriers, paving the way for therapeutic advancements with economic benefits.
Graphical Abstract
Enhanced optical pumping using mutually orthogonal magnetic fields for quantum sensing
Authors: Mandal Sudip , Singh Grewal Raghwinder , Pradhan Swarupananda 
Published: July 2024

Abstract
The atomic population trapped in irrelevant atomic states is a limiting factor for sensors based on laser-atom interaction. Using a bi-chromatic light field along with a specific combination of magnetic fields, we show a significant increase in the amplitude (i.e., more than seven times) of a two-photon coherent population trapping (CPT) resonance, which can be effectively used for atomic magnetometry. This increase in amplitude can be explained through enhanced optical pumping via the transfer of population to the relevant Zeeman states. Our experimental observations are consistent with the theoretical calculations carried out for a realistic three-level atomic system using density matrix formalism. We further discuss the optimum condition for enhanced optical pumping by adjusting the ground-state decoherence rate. Enhanced optical pumping through the manipulation of the magnetic field is quite important and is of great interest in the field of quantum technology.
Insulin Dynamics and Pathophysiology in Youth-Onset Type 2 Diabetes
Authors: Abu-Nejem Rozan , Hannon Tamara S 
Published: July 2024

Abstract
Youth-onset type 2 diabetes (T2D) is increasing around the globe. The mounting disease burden of youth-onset T2D portends substantial consequences for the health outcomes of young people and for health care systems. The pathophysiology of this condition is characterized by insulin resistance and initial insulin hypersecretion ± an inherent insulin secretory defect, with progressive loss of stimulated insulin secretion leading to pancreatic β-cell failure. Research studies focusing on youth-onset T2D have illuminated key differences for youth- vs adult-onset T2D, with youth having more profound insulin resistance and quicker progression to loss of sufficient insulin secretion to maintain euglycemia. There is a need for therapies that are targeted to improve both insulin resistance and, importantly, maintain sufficient insulin secretory function over the lifespan in youth-onset T2D.
Leadership Management Of The Chairman Foundation Coordinating Education Unit Management
Authors: Rasid Rasid , Nasir Nasir 
Published: July 2024

Problem: The governance of the education unit under the auspices of the foundation is not coordinated measurably in terms of milestones. Purpose: This paper provides direction for the leadership management strategy of the foundation’s chairman in coordinating the management of educational units. Methods: Collection of data and information using observation, direct interviews, the Delpy method, documentation, and physical artifacts. Inductive, process, and goal-oriented Result: the head of the foundation carries out a transformative leadership management strategy coordinating with the management strategy, and coordinating with the educational unit. The pattern of transformative leadership as a strategy for adapting a harmonious and productive democratic leadership model in mobilizing school principals and teachers to the demands of changes in the management information and technology-based education units, as well as student-oriented leadership strategy that emphasizes the quality of management of educational units under the foundation’s internal supervision, governance of quality-oriented foundations in educational units, developing the quality of teaching and educational staff resources, developing facilities and infrastructure, involving parent of students and benchmarking in educational unit at the same level.
Feasibility of implementing a remote system for lymphoedema conservative therapy: a case study
Authors: Matsumoto Chisato , Yang Rui , Okazaki Mutsumi , Konya Chizuko , Dai Misako 
Published: July 2024

Background: Poor access to lymphoedema specialists and communication between them and patients prevents appropriate lymphoedema management. Therefore, development and dissemination of remote systems is necessary to improve care in rural areas with limited medical personnel or access to medical coordination. Aims: The authors evaluated the elements required for providing patient education on conservative therapy for lymphoedema, to determine the feasibility of remote management. Methods: The study involved connecting a health professional in a local clinic (point A) treating a patient with lymphoedema, who was present alongside the clinician, with a specialist certified lymphoedema therapist (CLT) located remotely in a university (point B). Findings: The CLT was able to greet, interview and provide guidance to the patient on conservative therapy. Direct contact with the patient was not possible, which limited visualisation, palpation, leg circumference measurement, and lymphatic drainage management. Conclusion: The findings suggest that remote a lymphoedema management approach involving conservative therapy benefits both patients and health professionals, particularly in rural regions. Future studies are needed to confirm the effectiveness of this approach to confirm adequate treatment.
Experimental demonstration of a silicon four-mode (de)multiplexer based on cascaded triple-waveguide couplers
Authors: Yu Xiaojun , Jiang Weifeng 
Published: July 2024

Silicon photonics based on-chip mode-division multiplexing (MDM) is an appealing technology for enhancing the interconnect capacity in both short- and long-haul optical communication. Here, a silicon four-mode (de)multiplexer [(De)MUX] is proposed, optimized, fabricated, and characterized for on-chip MDM systems, based on three cascaded triple-waveguide couplers (TWCs), with coupling lengths below 24.25 µm. A four-mode MDM-link consisting of two back-to-back mode-(De)MUXs was fabricated and measured, yielding a crosstalk of less than −15.0dB over a bandwidth wider than 72.6 nm for four modes. In addition, the TWC based mode (De)MUX demonstrates a 1-dB bandwidth greater than 40 nm, and can be considered as a robust component for multimode on-chip networks.
Super broadband light source: a promising master oscillator source for high brightness and high-power fiber amplifiers
Authors: Chen Qi , Li Wei , Deng Yu , Chen Yisha , Liu Wei , Pan Zhiyong , Chen Zilun , Ma Pengfei , Wang Zefeng 
Published: July 2024

Stimulated Raman scattering (SRS) and transverse mode instability (TMI) effects are crucial limitation factors for further power scaling of high-power fiber amplifiers with near-diffraction-limited beam quality. It is an important research direction to carry out laser system optimization from the perspective of seed construction. In this work, we experimentally investigated the impact of utilizing different seed lasers on the SRS and TMI characteristics in high power ytterbium-doped fiber amplifiers. Both the phase modulated single frequency fiber laser (PMSFL), fiber oscillator laser (FOL), and superfluorescent fiber source (SFS) as a typical type of temporally stable broadband light source (SBLS) are employed as seed lasers. The experimental results indicated that the SRS intensity in the fiber amplifier is influenced by the properties of the seed laser source. Notably, the SRS threshold of the SBLS could be comparable to that of a low-noise PMSFL source. There is a significant increase in TMI threshold when employing SBLS as a seed laser in high-power fiber amplifiers, which is 3.86 times that of the injected seed laser with a 3 dB narrow linewidth of 0.74 nm. Considering the combined threshold characteristics of SRS and TMI, it can be found that SBLS is a promising master oscillator source for high brightness and high-power fiber amplifiers. Our work could provide a good reference for the selection of a master oscillator source, and we believe that it is an important direction to go beyond the power limitation of high-power fiber lasers by constructing a light source with broader spectral linewidth and temporal stability.