bluuebunny/crossref_metadata_2025 huggingface dataset:
Design, implementation and usability analysis of patient empowerment in ADLIFE project via patient reported outcome measures and shared decision making
Authors: Erturkmen Gokce B. Laleci , Juul Natassia Kamilla , Redondo Irati Erreguerena , Gil Ana Ortega , Berastegui Dolores Verdoy , de Manuel Esteban , Yuksel Mustafa , Sarigul Bunyamin , Yilmaz Gokhan , Choi Keung Sarah N. L. I. M. , Arvanitis Theodoros N. , Syse Thea Damkjaer , Bloemeke-Cammin Janika , Kaye Rachelle , Sorknæs Anne Dichmann ,   on behalf of the ADLIFE study group
Published: June 2024

Introduction

This paper outlines the design, implementation, and usability study results of the patient empowerment process for chronic disease management, using Patient Reported Outcome Measurements and Shared Decision-Making Processes.

Background

The ADLIFE project aims to develop innovative, digital health solutions to support personalized, integrated care for patients with severe long-term conditions such as Chronic Obstructive Pulmonary Disease, and/or Chronic Heart Failure. Successful long-term management of patients with chronic conditions requires active patient self-management and a proactive involvement of patients in their healthcare and treatment. This calls for a patient-provider partnership within an integrated system of collaborative care, supporting self-management, shared-decision making, collection of patient reported outcome measures, education, and follow-up.

Methods

ADLIFE follows an outcome-based and patient-centered approach where PROMs represent an especially valuable tool to evaluate the outcomes of the care delivered. We have selected 11 standardized PROMs for evaluating the most recent patients’ clinical context, enabling the decision-making process, and personalized care planning. The ADLIFE project implements the "SHARE approach’ for enabling shared decision-making via two digital platforms for healthcare professionals and patients. We have successfully integrated PROMs and shared decision-making processes into our digital toolbox, based on an international interoperability standard, namely HL7 FHIR. A usability study was conducted with 3 clinical sites with 20 users in total to gather feedback and to subsequently prioritize updates to the ADLIFE toolbox.

Results

User satisfaction is measured in the QUIS7 questionnaire on a 9-point scale in the following aspects: overall reaction, screen, terminology and tool feedback, learning, multimedia, training material and system capabilities. With all the average scores above 6 in all categories, most respondents have a positive reaction to the ADLIFE PEP platform and find it easy to use. We have identified shortcomings and have prioritized updates to the platform before clinical pilot studies are initiated.

Conclusions

Having finalized design, implementation, and pre-deployment usability studies, and updated the tool based on further feedback, our patient empowerment mechanisms enabled via PROMs and shared decision-making processes are ready to be piloted in clinal settings. Clinical studies will be conducted based at six healthcare settings across Spain, UK, Germany, Denmark, and Israel.
Platelet-derived exosomes alleviate tendon stem/progenitor cell senescence and ferroptosis by regulating AMPK/Nrf2/GPX4 signaling and improve tendon-bone junction regeneration in rats
Authors: Chen Deheng , Tang Qian , Song Wei , He Yaohua
Published: June 2024

Background

Tendon stem/progenitor cell (TSPC) senescence contributes to tendon degeneration and impaired tendon repair, resulting in age-related tendon disorders. Ferroptosis, a unique iron-dependent form of programmed cell death, might participate in the process of senescence. However, whether ferroptosis plays a role in TSPC senescence and tendon regeneration remains unclear. Recent studies reported that Platelet-derived exosomes (PL-Exos) might provide significant advantages in musculoskeletal regeneration and inflammation regulation. The effects and mechanism of PL-Exos on TSPC senescence and tendon regeneration are worthy of further study.

Methods

Herein, we examined the role of ferroptosis in the pathogenesis of TSPC senescence. PL-Exos were isolated and determined by TEM, particle size analysis, western blot and mass spectrometry identification. We investigated the function and underlying mechanisms of PL-Exos in TSPC senescence and ferroptosis via western blot, real-time quantitative polymerase chain reaction, and immunofluorescence analysis in vitro. Tendon regeneration was evaluated by HE staining, Safranin-O staining, and biomechanical tests in a rotator cuff tear model in rats.

Results

We discovered that ferroptosis was involved in senescent TSPCs. Furthermore, PL-Exos mitigated the aging phenotypes and ferroptosis of TSPCs induced by t-BHP and preserved their proliferation and tenogenic capacity. The in vivo animal results indicated that PL-Exos improved tendon-bone healing properties and mechanical strength. Mechanistically, PL-Exos activated AMPK phosphorylation and the downstream nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) signaling pathway, leading to the suppression of lipid peroxidation. AMPK inhibition or GPX4 inhibition blocked the protective effect of PL-Exos against t-BHP-induced ferroptosis and senescence.

Conclusion

In conclusion, ferroptosis might play a crucial role in TSPC aging. AMPK/Nrf2/GPX4 activation by PL-Exos was found to inhibit ferroptosis, consequently leading to the suppression of senescence in TSPCs. Our results provided new theoretical evidence for the potential application of PL-Exos to restrain tendon degeneration and promote tendon regeneration.
Improvements of 177Lu SPECT images from sparsely acquired projections by reconstruction with deep-learning-generated synthetic projections
Authors: Wikberg Emma , Essen Martijn van , Rydén Tobias , Svensson Johanna , Gjertsson Peter , Bernhardt Peter
Published: June 2024

Background

For dosimetry, the demand for whole-body SPECT/CT imaging, which require long acquisition durations with dual-head Anger cameras, is increasing. Here we evaluated sparsely acquired projections and assessed whether the addition of deep-learning-generated synthetic intermediate projections (SIPs) could improve the image quality while preserving dosimetric accuracy.

Methods

This study included 16 patients treated with 177Lu-DOTATATE with SPECT/CT imaging (120 projections, 120P) at four time points. Deep neural networks (CUSIPs) were designed and trained to compile 90 SIPs from 30 acquired projections (30P). The 120P, 30P, and three different CUSIP sets (30P + 90 SIPs) were reconstructed using Monte Carlo-based OSEM reconstruction (yielding 120P_rec, 30P_rec, and CUSIP_recs). The noise levels were visually compared. Quantitative measures of normalised root mean square error, normalised mean absolute error, peak signal-to-noise ratio, and structural similarity were evaluated, and kidney and bone marrow absorbed doses were estimated for each reconstruction set.

Results

The use of SIPs visually improved noise levels. All quantitative measures demonstrated high similarity between CUSIP sets and 120P. Linear regression showed nearly perfect concordance of the kidney and bone marrow absorbed doses for all reconstruction sets, compared to the doses of 120P_rec (R2 ≥ 0.97). Compared to 120P_rec, the mean relative difference in kidney absorbed dose, for all reconstruction sets, was within 3%. For bone marrow absorbed doses, there was a higher dissipation in relative differences, and CUSIP_recs outperformed 30P_rec in mean relative difference (within 4% compared to 9%). Kidney and bone marrow absorbed doses for 30P_rec were statistically significantly different from those of 120_rec, as opposed to the absorbed doses of the best performing CUSIP_rec, where no statistically significant difference was found.

Conclusion

When performing SPECT/CT reconstruction, the use of SIPs can substantially reduce acquisition durations in SPECT/CT imaging, enabling acquisition of multiple fields of view of high image quality with satisfactory dosimetric accuracy.
Labor migration, remittances, and the economy in the Gulf Cooperation Council region
Authors: Wagle Udaya R.
Published: June 2024

The massive increase in labor migration to the Middle East during the past three decades has rivaled its historical trends bound to the West. This paper assesses how this growing trend of migration may have helped shape the economic structure and performance across the member countries of the Gulf Cooperation Council. Findings from a descriptive and time series regression analysis of the limited cross-country data show that the experience with labor migration and its linkage with other aspects of the economy are varied. The migration trend coinciding with increasing personal remittances attests to the competitive demand for foreign labor. While labor migration shows mixed association with the key aspects of the economy, the stock of migrant population is negatively associated with economic growth. Albeit seemingly contradictory, the insights from this six-country analysis covering the periods since 1990 are useful to understand the complex nature of relationship between labor migration and economic structure and performance in the region.
Burden and trends of infectious disease mortality attributed to air pollution, unsafe water, sanitation, and hygiene, and non-optimal temperature globally and in different socio-demographic index regions
Authors: Liu Qiao , Deng Jie , Yan Wenxin , Qin Chenyuan , Du Min , Wang Yaping , Zhang Shimo , Liu Min , Liu Jue
Published: June 2024

Background

Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019.

Methods

This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019.

Results

In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65–69, 75–79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature.

Conclusions

Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively.
Triazophos toxicity induced histological abnormalities in Heteropneustes fossilis Bloch 1794 (Siluriformes: Heteropneustidae) organs and assessment of recovery response
Authors: Loganathan Kanniyappan , Tennyson Samuel , Arivoli Subramanian
Published: June 2024

Background

Agricultural pesticides have toxic effects in the aquatic ecosystem, and their persistence poses a hazard to aquatic life, as seen by fish poisoning, both acute and chronic. Triazophos, a broad-spectrum organophosphate insecticide, is used to control agricultural crops from insect pests. For a period of 10 days, Heteropneustes fossilis, a fish of great economic and therapeutic value, was exposed to various levels of triazophos toxicity (5, 10 and 15 ppm), after which they were sacrificed. For recovery tests, the treated fish were switched to clean tap water after 10 days of exposure to the toxicant, examined for another 10 days, and then sacrificed. The histological changes in the tissues of the sacrificed fishes' gill, liver, intestine, kidney, brain, and muscle (treatment and recovery) were investigated.

Results

The histology investigations revealed that the toxicant was hazardous, with histopathological changes increasing as the concentration of the toxicant increased. The gills had the most damage, with fusion of secondary lamella and epithelial hyperplasia; liver had vacuolization, pyknotic nuclei, and focal necrosis; intestine had degenerated, necrotic villi, degeneration of epithelial cells, and atropy; kidney had narrowing of the tubular lumen, pyknotic nuclei, hypertrophy, degeneration; swelling, haemorrhage, larger neuronal cells, and karyolysis were observed in the brain, whereas infiltration of leucocytes, loss of striated muscles, and an increase in intra fibril area were observed in the muscle. When compared to the treated fishes, the 10-day recovery research demonstrated tissue damage and a slower recovery pattern.

Conclusions

Triazophos caused histological changes in the gill, liver, intestine, kidney, brain and muscle of the test fish Heteropneustes fossilis. With reference to recovery response, a slow recovery was observed. Furthermore, this is the first investigation into the effects of triazophos on the recovery response in Heteropneustes fossilis.
Single-cell transcriptomic profiling reveals decreased ER protein Reticulon3 drives the progression of renal fibrosis
Authors: Guo Shuai , Dong Yi , Du Ran , Liu Yu-Xing , Liu Shu , Wang Qin , Liu Ji-Shi , Xu Hui , Jiang Yu-Jie , Hao Huang , Fan Liang-Liang , Xiang Rong
Published: June 2024

Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3’s role in CKD’s narrative and position it as a promising therapeutic contender.
Long term follow-up results of phase II clinical trial evaluating ruxolitinib (RUX) and azacitidine (AZA) combination therapy in patients (pts) with myelofibrosis (MF).
Authors: Arora Sankalp , Senapati Jayastu , Masarova Lucia , Pemmaraju Naveen , Bose Prithviraj , Bravo Guillermo Montalban , Saenz Dyana T , Halim Habiba , Zhou Lingsha , Maiti Abhishek , Borthakur Gautam , Kadia Tapan M. , Jabbour Elias , Garcia-Manero Guillermo , Kantarjian Hagop M. , Daver Naval Guastad
Published: June 2024

6572

Background: Monotherapy with JAK inhibitors improve spleen and symptom burden in MF, but their disease modifying effect is less clear. We conducted a phase 2 clinical trial evaluating the combination of RUX with hypomethylating agent AZA in MF. The interim analyses (Masarova et al.Blood, 2018) showed objective responses in 72% pts. We report the long-term follow-up of the full cohort of pts treated on this trial. Methods: The trial was conducted at MD Anderson Cancer Center, Houston including adult pts (≥ 18 years) with MF intermediate (Int) 1-2 or high-risk disease by Dynamic International Prognostic Scoring System (DIPSS). Responses were assessed per the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria. Results: From 3/2013-10/2021, 61 pts with a median age of 66 yrs (46-87) were treated (Table). Median Hb was 10.1 g/dl (6.8-16.2), and bone marrow blasts (BM) 2% (0-14%); 14 (23%) had BM blasts ≥ 5%. JAK 2 was mutated in 35 (57%); 38 pts (62%) had Int-2 or high risk DIPSS disease. IWG-MRT responses occurred in 44 pts (72%): clinical improvement (CI) in 37 (61%), including IWG-MRT CI spleen reduction >50% in 28/46 pts (61%) with baseline length ≥5 cm below left costal margin, and 31/51 pts (61%) with baseline TSS>12 having a >50% improvement in total symptom score (TSS 50). Partial response was seen in 4 pts and cytogenetic complete remission in 3 pts. With a median follow up of 93 mos, median overall survival (OS) was 46 mos (95% CI: 25-66), median event free survival was 33 mos (95% CI: 24-43) and median duration of any objective response was 43 mos (95% CI: 24-62). Transformation to AML occurred in 14 pts (23%) with median time to transformation of 19 mos (1-46). 20 pts (33%) received a stem cell transplant (SCT), 11 (55%) with Int-2/high risk DIPPS disease. Pts in the Int-2/high risk DIPPS group who got SCT had a trend towards improved median OS vs. those who did not (38 vs 27 mos, p=0.2). Grade ≥ 3 adverse events (AE) regardless of treatment attribution occurred in 30 pts (49%), most common were pneumonia (10,16%), anemia (7,12%), and sepsis (5, 8%). 3 pts had grade 5 AEs, and 4 pts were taken off study due to toxicity. Conclusions: Long term follow up data from this phase 2 clinical trial shows good efficacy of the AZA-RUX combination in MF, with durable responses and promising survival outcomes. Clinical trial information: NCT01787487 . [Table: see text]
Epcoritamab with rituximab + lenalidomide (R2) in previously untreated (1L) follicular lymphoma (FL) and epcoritamab maintenance in FL: EPCORE NHL-2 arms 6 and 7.
Authors: Lori Leslie A. , Falchi Lorenzo , Vermaat Joost S.P. , Musuraca Gerardo , Belada David , Nijland Marcel , Christensen Jacob Haaber , Offner Fritz , Hoehn Daniela , Marek Jennifer , Wang Liwei , Mei JP , Abrisqueta Pau , Brody Joshua D.
Published: June 2024

7014

Background: In 1L FL, more effective, less toxic treatment (tx) options that induce durable complete responses (CRs) are needed. For responders, novel maintenance approaches are needed to improve long-term outcomes. We present data from EPCORE™ NHL-2 (phase 1/2; NCT04663347), with longer follow-up for epcoritamab + R2 in 1L FL (arm 6) and the first disclosure for epcoritamab maintenance in patients (pts) with FL in CR or partial response (PR) after 1–2 lines of standard of care (SOC) tx (arm 7). Methods: Adults with CD20+ FL grade (G) 1–3A received subcutaneous epcoritamab 48 mg. In arm 6, pts received R2 for ≤12 cycles (Cs) of 28 d and epcoritamab (QW, C1–2; Q4W, C3–26). In arm 7, pts received epcoritamab (QW, C1 [28 d]; Q8W, C2–13 [56 d/C]). Pts received step-up epcoritamab dosing and corticosteroid prophylaxis in C1 to mitigate CRS. Primary endpoints were overall response rate (ORR; Lugano criteria) in arm 6 and safety/tolerability in arm 7. Results: As of Nov 22, 2023, 41 pts with 1L FL received epcoritamab + R2 (arm 6) and 20 pts in CR or PR after SOC tx received epcoritamab maintenance (arm 7). In arm 6 (median follow-up, 21.1 mo), median age was 57 y and 34% had FLIPI 3– 5. ORR was 95%; CR rate was 85%. The most common treatment-emergent AEs (TEAEs) were COVID-19 (63%), CRS (56%), and neutropenia (56%). CRS was low grade (41% G1, 15% G2) and resolved; most events occurred after the first full dose and none led to epcoritamab discontinuation. Two fatal TEAEs occurred (COVID-19 pneumonia and septic shock). In arm 7 (median follow-up, 19.7 mo), median age was 54.5 y and 25% had FLIPI 3–5; 60% had CR and 40% had PR with their last tx line. All pts had prior anti-CD20 tx, 80% had prior alkylating agents, and 50% had prior anthracyclines; 80% had 1 prior tx line. The most common TEAEs were COVID-19 (70%) and CRS (55%). CRS was G1 (40%) or G2 (15%) and resolved; events mostly occurred after the first full dose, and none led to tx discontinuation. One fatal TEAE occurred (respiratory failure; post-acute COVID syndrome after 2 Cs of tx). No ICANS or clinical tumor lysis syndrome occurred in either arm. Additional efficacy data are in Table. Conclusions: In arm 6, epcoritamab + R2 continued to show deep, durable responses in 1L FL; safety was manageable and consistent with prior reports. In arm 7, the first epcoritamab maintenance data in FL showed conversions from PR to CR, with manageable safety and no new safety signals. The data warrant further evaluation of epcoritamab-based, chemotherapy-free regimens in FL. Clinical trial information: NCT04663347 . [Table: see text]
Lisocabtagene maraleucel (liso-cel) in patients (pt) with R/R mantle cell lymphoma (MCL): Subgroup analyses by number of prior systemic lines of therapy (LOT) and by response to prior Bruton tyrosine kinase inhibitor (BTKi) from the TRANSCEND NHL 001 MCL cohort (TRANSCEND-MCL).
Authors: Palomba Maria Lia , Siddiqi Tanya , Gordon Leo I. , Kamdar Manali Kirtikumar , Lunning Matthew Alexander , Hirayama Alexandre V. , Abramson Jeremy S. , Arnason Jon , Ghosh Nilanjan , Mehta Amitkumar , Andreadis Charalambos , Solomon Scott R. , Kostic Ana , Singh Ashvin , Espinola Ricardo , Bhatnagar Rashmi , Raviele Anthony , Wang Michael
Published: June 2024

7016

Background: In the TRANSCEND-MCL (NCT02631044) primary analysis, the CD19-directed, CAR T cell product liso-cel demonstrated a high, durable CR rate (CRR) with manageable safety in pts with heavily pretreated R/R MCL. Here, we report outcomes by number of prior LOTs and by response to prior BTKi. Methods: Pts had PET-positive R/R MCL after ≥ 2 prior systemic LOTs, including BTKi, alkylating, and CD20-targeted agents. Pts received liso-cel after lymphodepleting chemotherapy. Bridging therapy was allowed. Primary endpoints were treatment-emergent AEs (TEAE) and ORR by independent review committee (IRC) per Lugano 2014 criteria; secondary endpoints included CRR, duration of response (DOR), PFS, and OS. Results: 88 pts received liso-cel. Median follow-up was 16.1 mo (range, 0.4–60.5). For all pts, CRR was 72%; median DOR, PFS, and OS were 15.7, 15.3, and 18.2 mo, respectively (Table). ORR, CRR, and median DOR, PFS, and OS were similar to all pts for most subgroups, but numerically lower in pts with ≥ 5 prior LOTs and pts refractory to prior BTKi. Grade (gr) ≥ 3 TEAEs ranged from 67–96% across subgroups, similar to all pts (86%); most common gr ≥ 3 TEAE was neutropenia (33–58%). Most cytokine release syndrome (CRS) and neurological events (NE) were gr 1–2 (Table) with no gr 5 CRS/NE. Gr ≥ 3 infection (11–19%) and prolonged cytopenia (32–50%) in subgroups were similar to all pts (15% and 40%). Cellular kinetics will be presented. Conclusions: In TRANSCEND-MCL, all subgroups benefited from liso-cel and responses were generally comparable to the overall population, with numerically shorter duration in pts with ≥ 5 prior LOTs and disease refractory to prior BTKi, supporting study of liso-cel in earlier LOTs. Clinical trial information: NCT02631044 . [Table: see text]
Deep-learning model for real-time prediction of recurrence in early-stage non-small cell lung cancer: A multi-modal approach.
Authors: Jung Hyun Ae , Lee Daehwan , Park Boram , Lee Kiwon , Lee Ho Yun , Kim Tae Jung , Jeon Yeong Jeong , Lee Junghee , Park Seong Yong , Cho Jong Ho , Kim Hong Kwan , Choi Yong Soo , Park Sehhoon , Sun Jong-Mu , Lee Se-Hoon , Ahn Jin Seok , Ahn Myung-Ju
Published: June 2024

8029

Background: The surveillance protocol for early-stage non-small cell lung cancer (NSCLC) is not contingent upon individualized risk factors for recurrence. Longitudinal risk calculation for the prediction of recurrence was based on circulating tumor DNA. This study aimed to develop a deep-learning model using comprehensive data from clinical practice for practical longitudinal monitoring. Methods: A multi-modal deep-learning model employing transformers was developed for real-time recurrence prediction using clinical, pathological, and molecular data at baseline, alongside longitudinal laboratory, and radiologic data during surveillance. Patients with histologically confirmed NSCLC (stage I-III) undergoing curative intent surgery between January 2020 and September 2022 were included. The collected data was divided into training, validation, and test sets in a 6:2:2 ratio. The primary outcome focused on predicting likelihood of recurrence within one year from the monitoring point. This study demonstrated the timely provision of risk scores (RADAR score), determined thresholds, and the corresponding Area Under the Curve (AUC). Results: A total of 14,345 patients were enrolled (10,262 with stage I, 2,380 with stage II, and 1,703 with stage III). The training, validation, and test sets comprised 8,578, 2,866, and 2,901 patients, respectively. The model incorporated 64 clinical-pathological-molecular factors at baseline, alongside longitudinal laboratory, and radiologic text data. Radiologic data of 177,246 was used (mean 12.4 chest CT scan per patient) during surveillance. Baseline RADAR score was 0.20 (standard deviation [Std] 0.17) in stage I, 0.51 (Std 0.20) in stage II, and 0.64 (Std 0.19) in stage III. The AUC for predicting relapse within one year from that monitoring point was 0.847 across all stages with the sensitivity of 80.6% and specificity of 74.4% (Table) (AUC=0.851 in stage I, AUC=0.763 in stage II, and AUC=0.721 in stage III). Conclusions: This pilot study introduces a deep-learning model utilizing multi-modal data from routine clinical practice for predicting relapse in early-stage NSCLC. It demonstrates the timely provision of risk score, RADAR score, to clinicians for recurrence prediction, potentially guiding risk- adapted surveillance strategies and aggressive adjuvant systemic treatment. Notably, the RADAR score exhibited a high prediction ability for relapse in stage I disease. [Table: see text]
Characteristics and clinical outcomes of US veterans with advanced non–small cell lung cancer (NSCLC) by KRAS subtype: A National Veterans Health Administration analysis.
Authors: Anderson Clare E. , Scobie Micaela R , Zhou Katherine I. , Maddox Mark , Kelley Michael J. , Lin Chenyu
Published: June 2024

8581

Background: KRAS mutations have historically carried a poor prognosis in NSCLC. The most common variant, G12C, had similar survival compared to non-G12C variants. However, new KRAS G12C inhibitors have since been approved. This national VHA study evaluates the outcomes of KRAS-mutated advanced NSCLC by KRAS subtype in the era of KRAS G12C inhibitors. Methods: Patients with unresectable or metastatic NSCLC and a KRAS mutation detected between 2021-2022 were identified from the VA National Precision Oncology Program database. Analysis utilized Fisher’s exact test, logistic regression, and Cox regression. Results: 841 patients across 107 VA medical centers met search criteria. The median age was 73, and 95% were male. 21% were non-Hispanic black, 70% non-Hispanic white, and 2.5% Hispanic. 4% were never smokers. The most common KRAS mutations were G12C (35%), G12V (18%), G12D (13%), G12A (6%), Q61H (4%), and G13D (4%). The most common co-mutations to KRAS were TP53 (54%), STK11 (28%), KEAP1 (16%), and BRAF (3%). KEAP1 mutations more frequently co-occurred with KRAS Q61H (p=0.048), while BRAF mutations were more commonly seen with KRAS G13D (p=0.02) and G13C (p=0.01). In univariable analysis of overall survival (OS), KRAS G12C had a favorable OS compared to all non-G12C variants (HR 0.77, 95% CI 0.64-0.93, p=0.006). Specifically, KRAS G12D (HR 1.35, CI 1.03-1.76, p=0.03) and G12V (HR 1.42, CI 1.10-1.81, p=0.006) had significantly worse OS compared to G12C. Higher PDL1 TPS (HR 0.997, CI 0.995-0.999, p=0.02) and higher TMB (HR 0.96, CI 0.95-0.98, p<0.0001) had better OS, while older age (HR 1.02, CI 1.01-1.03, p=0.004) and co-mutations in KEAP1 (HR 1.60, CI 1.28-1.97, p<0.0001) and STK11 (HR 1.57, CI 1.31-1.88, p<0.0001) had worse OS. Social deprivation index (SDI, calculated by zip code), race/ethnicity, rural residence, and other co-mutations did not affect survival. In multivariable Cox regression, age (HR 1.02, CI 1.003-1.03), KRAS G12C (HR 0.74, CI 0.58-0.93), TMB (HR 0.97, CI 0.95-0.98), and STK11 (HR 1.62, CI 1.23-2.12) retained their association, while KEAP1 and PDL1 were no longer significant. Use of sotorasib had a borderline association with improved survival in univariable analysis (HR 0.74, CI 0.52-1.02). After adjusting for sotorasib in the multivariable model, the association of G12C with OS was no longer significant. In KRAS G12C NSCLC receiving at least 2 lines of therapy (n=90), the likelihood of receiving sotorasib did not differ by age, SDI, gender, race/ethnicity, or rural vs. urban residence. Only a history of economic instability (by ICD10 code) was associated with a lower likelihood of getting sotorasib (OR 0.22, 95% CI 0.03-0.91). Conclusions: In this cohort, KRAS G12C appears to confer a favorable prognosis compared to non-G12C variants, which may be explained in part by the adoption of sotorasib.
The Prevalence of Obstructive Sleep Apnea in Patients With Primary Aldosteronism
Authors: Sheu Jia-Yuh , Chang Li-Yang , Chen Jui-Yi , Chuang Min-Hsiang , Wu Vin-Cent , Chueh Jeff S
Published: June 2024

Context

Investigating the co-occurrence of obstructive sleep apnea (OSA) and primary aldosteronism (PA) is crucial for understanding their interrelation.

Objective

This work aimed to evaluate the prevalence of OSA in individuals diagnosed with PA and to assess the prevalence of PA within the OSA population, with a specific focus on hypertensive individuals.

Methods

An exhaustive search was performed across PubMed, Embase, CINAHL, Scopus, and Web of Science up to September 2023, without restrictions on language or publication date. Studies were selected based on their focus on the prevalence of OSA in PA patients and vice versa, specifically in hypertensive individuals. Data were extracted using standard guidelines, focusing on patient characteristics, prevalence rates, and other relevant clinical parameters.

Results

Proportional meta-analysis using a random-effects model revealed a 59.8% prevalence of OSA in hypertensive PA patients, with 45.4% exhibiting moderate-to-severe OSA. Meta-regression showed no significant effect of age, sex, body mass index, antihypertensive medication, systolic blood pressure, diastolic blood pressure, or serum potassium on OSA prevalence. However, a significant positive association was found with the glomerular filtration rate (GFR) (P < .001). Subgroup analysis also revealed that a hyperfiltration rate (GFR ≥ 100 mL/min per 1.73 m2) may be associated with a higher prevalence of OSA (71%, P value for interaction < .01). Among hypertensive OSA patients, 11.2% had PA.

Conclusion

A substantial prevalence of OSA in individuals with PA was identified, demonstrating a complex interplay between these conditions in hypertensive patients. Notably, the prevalence of OSA was significantly associated with kidney hyperfiltration.
Whole-exome Sequencing of Atypical Parathyroid Tumors Detects Novel and Common Genes Linked to Parathyroid Tumorigenesis
Authors: Pardi Elena , Poma Anello Marcello , Torregrossa Liborio , Pierotti Laura , Borsari Simona , Della Valentina Simone , Marcocci Claudio , Cetani Filomena
Published: June 2024

Context

Atypical parathyroid tumor (APT) represents a neoplasm characterized by histological features typical of parathyroid carcinoma (PC) but lacking local infiltration and/or distant metastasis, leading to uncertainty regarding its malignant potential.

Objective

To characterize the molecular landscape and deregulated pathways in APT.

Methods

Whole-exome sequencing (WES) was conducted on 16 APTs. DNA from tumors and matched peripheral blood underwent WES using Illumina HiSeq3000.

Results

A total of 192 nonsynonymous variants were identified. The median number of protein-altering mutations was 9. The most frequently mutated genes included BCOR, CLMN, EZH1, JAM2, KRTAP13-3, MUC16, MUC19, and OR1S1. Seventeen mutated genes belong to the Cancer Gene Census list. The most consistent hub genes identified through STRING network analysis were ATM, COL4A5, EZH2, MED12, MEN1, MTOR, PI3, PIK3CA, PIK3CB, and UBR5. Deregulated pathways included the PI3 K/AKT/mTOR pathway, Wnt signaling, and extracellular matrix organization. Variants in genes such as MEN1, CDC73, EZH2, PIK3CA, and MTOR, previously reported as established or putative/candidate driver genes in benign adenoma (PA) and/or PC, were also identified in APT.

Conclusion

APT does not appear to have a specific molecular signature but shares genomic alterations with both PA and PC. The incidence of CDC73 mutations is low, and it remains unclear whether these mutations are associated with a higher risk of recurrence. Our study confirms that PI3 K/AKT/mTOR and Wnt signaling represents the pivotal pathways in parathyroid tumorigenesis and also revealed mutations in key epigenetic modifier genes (BCOR, KDM2A, MBD4, and EZH2) involved in chromatin remodeling, DNA, and histone methylation.
Vigorous Exercise in Patients with Hypertrophic Cardiomyopathy
Authors: Fox Nolan , Fox Nicholas , Jacobsen Alan P. , Blumenthal Roger S. , Barouch Lili A.
Published: June 2024

Hypertrophic cardiomyopathy is a genetic heart condition occurring in up to 1 in 200 patients in the United States, many of whom are young and otherwise healthy. This condition puts those affected at increased risk for adverse cardiac outcomes, including sudden cardiac arrest and death, with particular concern for this to occur during exercise and other forms of exertion. Recent studies aimed at evaluating the risk of exercise in hypertrophic cardiomyopathy patients have suggested that moderate and even vigorous exercise may be safe for certain patients. Clinical guidelines are changing to reflect this recent information and to encourage a shared decision-making approach, which can allow more hypertrophic cardiomyopathy patients to participate in health-promoting exercise activities.
Delayed Overshooting: The Case for Information Rigidities
Authors: Müller Gernot J. , Wolf Martin , Hettig Thomas
Published: June 2024

We provide evidence that the delayed overshooting puzzle reflects a slow adjustment of exchange rate expectations to monetary policy shocks rather than a failure of uncovered interest parity. Consistent with this evidence, we put forward a New Keynesian model in which uncovered interest parity holds, but there are information rigidities: investors do not observe monetary policy shocks but learn rationally from unanticipated shifts in monetary policy about the state of the economy. We estimate the model and find it can account for the joint responses of the spot exchange rate, forward exchange rates, and excess currency returns to monetary policy shocks. (JEL D83, E12, E31, E43, E52, F31)
Discrete measurements of RNA polymerase and reverse transcriptase fidelity reveal evolutionary tuning
Authors: Potapov Vladimir , Krudup Stanislas , Maguire Sean , Unlu Irem , Guan Shengxi , Buss Jackson A. , Smail Benedict A. , van Eeuwen Trevor , Taylor Martin S. , Burns Kathleen H. , Ong Jennifer L. , Trachman Robert J.
Published: June 2024

Direct methods for determining the fidelity of DNA polymerases are robust, with relatively little sample manipulation before sequencing. In contrast, methods for measuring RNA polymerase and reverse transcriptase fidelities are complicated by additional preparation steps that introduce ambiguity and error. Here, we describe a sequencing method, termed Roll-Seq, for simultaneously determining the individual fidelities of RNA polymerases and reverse transcriptases (RT) using Pacific Biosciences single molecule real-time sequencing. By using reverse transcriptases with high rolling-circle activity, Roll-Seq generates long concatemeric cDNA from a circular RNA template. To discern the origin of a mutation, errors are recorded and determined to occur within a single concatemer (reverse transcriptase error) or all concatemers (RNA polymerase error) over the cDNA strand. We used Roll-Seq to measure the fidelities of T7 RNA polymerases, a Group II intron-encoded RT (Induro), and two LINE RTs (Fasciolopsis buskiR2-RT and human LINE-1). Substitution rates for Induro and R2-RT are the same for cDNA and second-strand synthesis while LINE-1 has 2.5-fold lower fidelity when performing second-strand synthesis. Deletion and insertion rates increase for all RTs during second-strand synthesis. In addition, we find that a structured RNA template impacts fidelity for both RNA polymerase and RT. The accuracy and precision of Roll-Seq enable this method to be applied as a complementary analysis to structural and mechanistic characterization of RNA polymerases and reverse transcriptases or as a screening method for RNAP and RT fidelity.
Journal Citation Report 2024 and Impact Factor of Pakistani Biomedical Journals: Grading impact and analysis
Authors: Meo Sultan Ayoub , Jawaid Shaukat Ali
Published: June 2024

doi: https://doi.org/10.12669/pjms.40.7.10399
How to cite this: Sultan Ayoub Meo1, Shaukat Ali Jawaid2. Journal Citation Report 2024 and Impact Factor of Pakistani Biomedical Journals: Grading impact and analysis. Pak J Med Sci. 2024;40(7):1315-1318. doi: https://doi.org/10.12669/pjms.40.7.10399
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Operational Cost Efficiency and Profitability Effects on Companies Distribution Stock Prices During Covid-19
Authors:   Entrepreneurship Department, BINUS Business School Undergraduate Program, Bina Nusantara University, Jakarta, Putra Raden Aditya Kristamtomo , Persada Satria Fadil , Kumalasari Riesta Devi , Herdina Ajeng Mira , Sekardhani Mufida , Razif Mohammad ,   Environmental Engineering Department, Institut Teknologi Adhi Tama Surabaya, Surabaya
Published: June 2024

Abstract. This study was conducted to determine whether the efficiency of operating costs and profitability of companies listed on the Indonesia Stock Exchange in the banking sector on stock prices. Research design, data, and methodology: This study uses 35 banking companies from 2020 to 2021 as a sample in the study, with a total of 70 financial statements data. The analysis test was conducted to see the effect of operational cost efficiency and profitability on stock prices in banking companies during the covid-19 pandemic. Multiple linier regression is conducted to check the simultaneous test and partial test. As for the indicators in cost efficiencies are operating expenses on operating income. The profitability effects indicators are based on return on equity. Stock prices indicators are based on internal and external policies and abilities. The test results show that operational cost efficiency and profitability have a simultaneous effect on stock prices. However, it partially shows that operational cost efficiency has no significant effect. Meanwhile, profitability shows positive results and has a significant effect. Conclusions: Based on the table of the Coefficient of Determination (R²) test, the value of Adjusted R Square is 98.7%. This shows that the variables of Operational Cost Efficiency and Profitability affect the stock price by 98.7% and the remaining 1.3% is influenced by other variables. Practical perspectives are further discussed in the paper. Keywords: Operation cost efficiency, profitability effects, stock prices, multiple linier regression, banking sector
Atomic Layer Deposition of h-BN(0001) for Passivation on Germanium and Lithium Garnet Substrates and Oxygen Radical Surface Interactions
Authors:   , Omolere Olatomide Bamidele
Published: June 2024

Boron nitride (BN) protective coatings have found extensive use in electrochemical batteries. Atomic layer deposition (ALD) was employed to deposit a thin BN layer onto solid Li-garnet electrolytes, utilizing a halide-free precursor, tris(dimethylamino)borane, and NH3 at 723 K. This process resulted in a 3 nm BN cap that effectively prevented Li2CO3 formation, a detrimental compound within Li-based electrolytes. The BN-coated Li-garnets exhibited remarkable stability under ambient conditions, confirmed through X-ray photoelectron spectroscopy (XPS) analysis, lasting for over 2 months. Moreover, the BN coating played a crucial role in stabilizing the Li anode/electrolyte interface, significantly reducing interfacial resistance to 18 Ω·cm². This enhancement increased critical current density and demonstrated impressive capacitance retention, exceeding 98% over 100 cycles. This research highlights the essential role of ALD in ensuring uniform BN growth. This precision is vital for suppressing Li dendrite growth, which has the potential to extend battery lifespan and enhance overall performance. The examination of oxygen radicals' interactions with surfaces holds crucial technological significance across diverse applications, including surface modification, microelectronics processing, thin film deposition, and space technologies. Ab initio molecular dynamics (AIMD) simulations are a potent tool for exploring bond-breaking pathways initiated by O radicals. These simulations provide detailed insights into how these pathways evolve concerning radical kinetic energy and trajectory. They effectively scrutinize reactions induced by oxygen radicals with varying kinetic energies, whether they are in their ground state (O 3P) or excited state (O 1D). Moreover, this discussion introduces novel calculations that reveal the potential for similar reaction products by adjusting kinetic energy in ground state oxygen or reducing kinetic energy in excited state oxygen. This energy modulation helps overcome activation barriers governing specific bond-breaking events within model systems. Germanium (Ge) is emerging as a potential Si replacement in high-performance CMOS technology. However, Ge's native oxide layer is less stable than Si's, limiting its semiconductor applications. Achieving an oxygen-free Ge surface is challenging. In-situ XPS revealed atomic oxygen's effectiveness at removing surface hydrocarbons at room temp. Atomic hydrogen at 350°C removes germanium oxide (GeO2). ALD of 3-monolayer h-BN film was deposited using tris (dimethyl amino) borane and NH3 at 450°C using ALD. XPS analysis showed it shields the Ge substrate from room-temp atomic oxygen oxidation, with only the outermost BN layer oxidizing. This is the first report of ALD-deposited h-BN on Ge surfaces. Atomic oxygen from a thermal cracker effectively removes carbon contaminants from a Ge surface exposed to room temperature ambient conditions.
Pillar/Perfusion Plates for Miniature Human Tissue Culture and Predictive Compound Screening
Authors:   , Kang Sooyeon
Published: June 2024

Human organoids have potential to revolutionize in vitro disease modeling by providing multicellular architecture and functional that are similar to those in vivo. Nonetheless, organoid-based, high-throughput screening (HTS) of compounds is challenged by lack of easy-to-use fluidic systems that are compatible with relatively large organoids. Therefore, we first fabricated a pillar plate, which was coupled with a complementary deep well plate and a perfusion well plate for static and dynamic culture via injection molding. We established various cell loading methods in hydrogels on the pillar plate. In addition, we investigated the effect of flow on the necrotic core of spheroids in the pillar/perfusion plate. Finally, we developed microarray three-dimensional (3D) bioprinting technology using the pillar and perfusion plates for human organoid culture and analysis. High-precision, high-throughput stem cell printing and encapsulation techniques were demonstrated on a pillar plate, which was coupled with a complementary deep well plate and a perfusion well plate for static and dynamic organoid culture. Bioprinted cells and spheroids in hydrogels were differentiated into organoids for in situ functional assays. The pillar/perfusion plates are compatible with standard 384-well plates and HTS equipment, and thus may be easily adopted in current drug discovery efforts.
Ethica Existentae
Authors:   , Serban Zeno
Published: June 2024

The aim of this dissertation is to provide a robust theory of environmental ethics which can offer nuanced accounts of value while evading the central problem of subjective disagreement that plagues other theories. The theory in question has many names, but the best abstraction of it can be found in the term "ontocentrism." Like pure biocentrism, this theory locates a monist center of value around which all other theorizations may orbit. Unlike biocentrism, however, this theory is not satisfied by anything short of the most basic commonality between valuable entities. That most basic value is existence, and it is taken to be the ground for all other values. This proposed theory, along with the methodology suggested, will be argued to be the next, if not final, step in theorization about environmental ethics. Due to the ubiquity of existence, however, this monism, as will be shown in detail later, paradoxically also appears to behave as a pluralist account of value would, wherein different positive accounts of value(s) are all affirmed. Therefore, despite being objectivist about value, it makes short work of the relativistic situations that are often brought to bear against objectivist accounts. This theory does not wish to abstract from the details of the world, and thus aim for some unattainable lack of bias, but rather it incorporates as many details about the world as possible such that any biases that may exist will be overwhelmed by the diversity of inputs which enter it. Any and all positive accounts of value have a prima-facie reason to be taken seriously, if not ultimately upheld. Since there is such a multiplicity of potential referents towards which value may be ascribed, there seems to be only, if one is not to impose preference on others, one way of impartially ascribing value; and that is equally. Thus, more complex entities will tend to have a greater number of potential referents of value, and therefore more value under this system. The intrinsic existential value of some specific entity can then be summed with the intrinsic existential value that that entity's continued existence will create or destroy in the specified future, often called extrinsic value, and this yields the total value that can inform our decisions.