bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase 1/2 trial of the XPO1 inhibitor selinexor in combination with docetaxel in previously treated, advanced KRAS mutant non-small cell lung cancer (NSCLC).
Authors: von Itzstein Mitchell S. , Burns Timothy F. , Dowell Jonathan , Horn Leora , Camidge David Ross , York Sally J. , Eaton Keith D. , Walker Christopher James , Zhang Song , Gerber David E
Published: June 2024

8597

Background: KRAS mutant NSCLC remains a therapeutic challenge. Although KRAS G12C inhibitors are now approved for cases harboring that specific mutation, their efficacy is modest and the G12C variant accounts for only 40% of KRAS mutations in NSCLC. To date, there are no approved targeted therapies for non-G12C KRAS mutant NSCLC. Selective inhibitors of nuclear export (SINE) modulate cancer cell biology by retaining certain proteins—such as tumor suppressors—within the nucleus, where they remain physiologically active. The XPO1 inhibitor selinexor demonstrated efficacyinpreclinicalNSCLC models harboring various KRAS mutations. Methods: In this 3 + 3 dose-escalation phase 1/2 trial, patients with previously treated advanced KRAS mutant NSCLC received selinexor (dosed orally weekly) plus docetaxel 75 mg/m2 IV every three weeks (NCT03095612). Prior treatment with KRAS G12C inhibitors was permitted. Results: Among 40 enrolled patients, median age was 66 years, 22 (55%) were female, and 34 (85%) were white. KRAS mutation types included G12C (28%), G12V (23%), G12D (20%), G12A (13%), G12R (5%), G13C (5%), and one case each of G12S, G13D, Q61L, and K117N. Patients had received a median of 2 prior lines of therapy (range 1-4). The maximum tolerated dose of selinexor was 60 mg PO weekly combined with docetaxel. The most common adverse events (AE) were nausea (73%, Gr ≥3 8%), fatigue (70%, Gr ≥3 5%), neutropenia (65%, Gr ≥3 60%), diarrhea (58%, Gr ≥3 10%), anorexia (50%, Gr ≥3 0%), and vomiting (45%, Gr ≥3 5%). Of 32 patients evaluable for efficacy, 7 (22%) had partial response (PR) and 18 (56%) had stable disease (SD) as best response. Median progression-free survival (PFS) was 4.1 months (95% CI, 2.9-5 months); median overall survival (OS) was 7.1 months (95% CI, 4.5-13.7 months). Clinical outcomes did not differ significantly among KRAS mutation types. However, TP53co-mutations (48%) were associated with significantly worse outcomes: disease control rate (PR + SD) 27% vs 92% ( P=0.006); median PFS 1.8 vs 7.4 months ( P<0.001); median OS 5.8 vs 17 months ( P=0.006). Additional biomarker studies are ongoing. Conclusions: Selinexor plus docetaxel is tolerated with multi-agent supportive care. The combination shows moderate efficacy across KRAS mutation types, with promising activity in TP53 wild type cases. Clinical trial information: NCT03095612 .
Association of human leukocyte antigen (HLA) status with immune checkpoint inhibitor (ICI) pneumonitis in patients with non-small cell lung cancer (NSCLC).
Authors: Li Molly SC , Cheung Alvin HK , Mui Zeta , Chow Chit , Lau Yat Ming , Wong Kit Yee , Kang Wei , To Ka Fai , Mok Tony S. K.
Published: June 2024

8620

Background: Pneumonitis is a potentially serious complication occurring in 5-20% of lung cancer patients receiving ICI. The genetic risk factors for ICI pneumonitis are unclear. Given the association between HLA genetic variants and autoimmune diseases, we hypothesized that certain HLA genetic variants are associated with risk of ICI pneumonitis. Methods: Patients with advanced EGFR/ ALK wild type, PD-L1 tumor proportion score ≥50% NSCLC who received ICI were enrolled from year 2019 to 2022. Germline HLA typing was performed on buccal swab specimens using the Alltype Fastplex assay. Clinicopathological characteristics, treatment courses and survival outcomes were retrospectively collated. The primary endpoint was the correlation of common HLA variants (present in >30% of subjects) to the risk of ICI pneumonitis. Results: 42 patients (all Chinese, 36 male, 33 current/former smokers) were enrolled. Median age was 71 years old (range 51-91). 34, 6, 1 and 1 patients had adenocarcinoma, NSCLC not otherwise specified, squamous cell carcinoma and large cell neuroendocrine carcinoma respectively. Majority (33/42, 79%) received pembrolizumab monotherapy while 9 (21%) patients received pembrolizumab plus chemotherapy. Median follow up time was 27.8 months. At data cutoff, 28 (67%) patients received ICI for more than 1 year and 10 (24%) patients stopped ICI after completion of 2-year course of treatment. Seven (17%) patients developed pneumonitis, of which 3 were grade 2 and 4 were grade 3 in severity. Median time to development of pneumonitis was 6.9 months (range 0.3-25.2). Demographic characteristics were similar between patients who did or did not experience pneumonitis. In the entire cohort, twenty-two (52%) patients harbored the class II DPB1*02 allele. This allele was significantly associated with development of ICI pneumonitis. All 7 patients who had ICI pneumonitis harbored the DPB1*02 allele. The incidence of pneumonitis in patients harboring the DPB1*02 allele was 32% compared to 0% in those without this allele (p=0.009). Patients who experienced pneumonitis had worse survival rates than those without (p=0.03), but expression of DPB1*02 allele was not associated with inferior survival outcomes. Conclusions: Our results suggested that expression of DPB1*02 allele may be associated with development of ICI pneumonitis. A larger case-control study is ongoing to validate this association. [Table: see text]
Clinical impact of the rapid genomic screening platform for non-small cell lung cancer in Asia-Pacific (LC-SCRUM-AP).
Authors: Umemura Shigeki , Kuo Chih-Hsi , Sriuranpong Virote , Thiagarajan Muthukkumaran , Akewanlop Charuwan , Murata Yuri , Shibata Yuji , Prae Methaneethorn , Ikeda Tatsuya , Egami Kaori , Chase Genevieve , Svedman Christer , Seto Takashi , Izumi Hiroki , Matsumoto Shingo , Goto Koichi
Published: June 2024

8637

Background: In 2013, a lung cancer genomic screening project (LC-SCRUM-Asia) started in Japan and expanded to other Asia-Pacific countries in October 2022 (LC-SCRUM-AP). The objective of this study is to clarify the characteristics of genomic profile in Asia-Pacific countries outside of Japan and to elucidate the clinical significance of rapid genomic screening. Methods: To shorten the turnaround time (TAT), a central laboratory was set in each participating country. Samples are analyzed by a multi-gene PCR assay and a rapid next-generation sequencing assay. Clinical, pathological and genomic data are stocked as a clinical-genomic database in each participating country, which is combined with Japanese database and the integrated clinical-genomic database of the Asia-Pacific region was established. Results: A multi-gene PCR assay data was available in 7879 samples from 4 Asia-Pacific countries (Taiwan/Thailand/Malaysia/Japan = 126/65/30/7658 pts). The rates of driver alterations in never-smokers with non-squamous histology were similar in the 4 Asia-Pacific countries: 83%, 80%, 89% and 75% in Taiwan, Thailand, Malaysia, and Japan, respectively. The pattern of genomic profile was also similar among these 4 countries. The median TAT was 4 days and 5 days in Japanese cohort and Taiwan/Thailand/Malaysia cohort, respectively. In Taiwan/Thailand/Malaysia cohort (n = 221), the genomic analysis successful rate was 99.5%. The rates of genomic alterations detected: EGFR (35%) of which ex20ins (6%), KRAS (10%) of which G12C (4%), ALK fusions (6%), ROS1 fusions (4%), RETfusions (0.5%), HER2ex20ins (4%), MET ex14skip (3%), BRAF V600E (1.5%), and NTRK3 fusions (0.5%). Oncogenic driver alterations were detected in 149 pts, of which 102 (68%) pts received targeted therapies approved in each country. 14 patients were enrolled into clinical trials of the investigational drugs, of which 5 were for targeting rare driver alterations. Conclusions: LC-SCRUM-AP is the first international genomic screening platform established in the Asia-Pacific region, which enables the efficient detection of rare driver alterations with a short TAT, contributing to the high implementation rate of targeted therapies. The similar pattern of genomic profile in the 4 Asia-Pacific countries indicates the utility of this screening platform as the basis for the clinical trials for NSCLC with rare driver alterations. We plan to further expand the number of institutions and participating countries.
Implementing a research methods curriculum for first year hematology oncology fellows.
Authors: Sharafeldin Noha , May Jori E. , Williams Grant Richard , Abuali Inas
Published: June 2024

9034

Background: The Hematology/Oncology Fellowship Program at the University of Alabama at Birmingham is an ACGME accredited, three-year academic training program. Fellows are expected to participate in at least one mentored research project during their second and third years of training. The program, however, did not provide formal training in research methods. Here, we provide the results of implementing a research methods curriculum for first year fellows to fulfill that educational need and to facilitate engagement in research projects throughout their fellowship training. Methods: We developed a structured curriculum composed of 10 didactic sessions covering the fundamental concepts of epidemiology and biostatistics. Based on the core competencies of research methods, learning objectives integrated concepts of 1) study design; 2) identifying bias and confounding; 3) exploratory data analysis, statistical inference, hypothesis testing; and results interpretation; and 4) critical appraisal of research evidence. The course was designed to promote self-directed learning and build on individual experiences and interests. One-on-one meetings between curriculum faculty and fellows facilitated identification of fellow research interests and pairing with mentors with aligned expertise. The didactic sessions were evaluated using a 21 question pre- and post- knowledge assessment. Fellows also self-rated on a 10-point scale their level of confidence performing research related activities. Following the course, fellows were expected to complete at least i) one research project, present it at a scientific meeting and submit for publication in peer-reviewed journal; and/or ii) one research proposal grant application. Results: To date, 13 first-year fellows across three cohorts have participated in the course, two of which have been completed, and the third will conclude in March 2024. Complete pre- and post- assessment scores were available for 8 fellows. Mean score difference was statistically significant comparing pre- to post- knowledge scores (3.79 points (SD= 4.43), paired t-test p-value=0.02). Self- ratings improved across all components on average from 3.7 pre- to 6.5 post-course (p<0.001). The largest change in self-ratings were in understanding study design concepts, basic principles of research and critical appraisal, followed by interpreting statistical outputs. All fellows are leading at least one mentored research project and 7 out of 8 fellows have presented abstracts at national meetings including the American Society of Clinical Oncology and the American Society of Hematology. Conclusions: Implementing a dedicated research methods curriculum to clinical fellows is feasible, and improved learner knowledge, skills, and engagement in research activities. Research methods principles can be effectively incorporated into the first year of clinical fellowship training.
Predictive factors for academic oncology career placement.
Authors: Wei John X. , Yan John , Beltran Santiago , Castellucci Enrico
Published: June 2024

9039

Background: Oncology is a discipline that has witnessed rapid expansion with new therapeutics and practices. Following this trend, training programs are increasingly valuing the cultivation of academic oncologists who will contribute to these developments through research. This study aims to explore characteristics of fellowship programs in the US promoting academic careers in oncology (initial academic position). Methods: A sampling of graduated fellow profiles available on the public websites of US hematology-oncology programs was conducted. To minimize over-representation from programs, even sampling of all available graduated fellows by year was done with a maximum of 10 per program. Characteristics including demographics, educational background, google scholar publication count during fellowship (divided into quartiles), program characteristics, and initial job (academics vs private practice) were collected. Academics was defined as working for an institution associated with a medical school. Logistic regression modeling was utilized to identify characteristics associated with higher odds of initial academic placement. Results: Between 2007 and 2023, 564 graduated fellows were identified, making up 39% of programs, with a majority favoring more recent years. Fellows graduating from NCI cancer center-associated programs and those of academic programs had significantly higher odds of obtaining an initial academic position (OR 1.60, 95% CI 1.08-2.38, p <0.05; OR 2.25, 95% CI 1.22-4.30, p <0.05). The strongest association was noted with scholarly productivity. Fellows of the highest quartile of productivity during their fellowship years (OR 9.70, 4.94-19.80, p <0.001) had the highest odds of obtaining an initial academic position. Characteristics without significant association included type of medical school (US vs IMG) and gender. Conclusions: Our data shows several characteristics associated with higher odds of initial academic placement, but most prominently, fellows of the highest quartile of research productivity were more than nine times likely than those of the lowest quartile of research productivity to obtain an academic position after fellowship. Our study is limited by its observational nature, but the magnitude and significance of association is worth investigating further and can shed light on the value of fellowship academic initiatives to foster research development. Select variables of a logistic regression model examining characteristics associated with obtaining an initial academic position after fellowship. Gender and Medical School status not included. [Table: see text]
Cracking the code: Can bibliometric attributes predict NIH R01 grant funding outcomes in gastrointestinal oncology? Exploring patterns from a five-year analysis.
Authors: Khan Sara Ahmed , Eshaghi Faraz , Rehman Mohammed Z , Kotwal Serena , Salama Amy , Khan Kainat , Farooq Muhammad Zain , Kumar Kapisthalam
Published: June 2024

9051

Background: The allocation of National Institutes of Health (NIH) R01 grants holds paramount importance for principal investigators in the field of scientific research. In this study, we explore the relationship between bibliometric attributes of principal investigators- specifically H-index, citations, publications, and seniority with the amount of NIH grant funding for R01 grants under gastrointestinal oncology from the fiscal years of 2018 to 2022. Understanding these interrelationships is crucial for researchers aiming to enhance their profiles to secure higher funding amounts from the NIH. Methods: The data was retrieved from the NIH RePORTER (Research Portfolio Online Reporting Tools Expenditure) using gastrointestinal oncology-related search terms from 2018-2022. The number of citations, publications, H-index, and seniority were obtained from Scopus. The bibliometric attributes of principal investigators were correlated with NIH grant funding amounts. Multiple regression analysis was employed to quantify the predictive power. Additionally, t-tests were performed to examine the significant differences in grant funding between high and low h-index groups. Results: A total of 1652 principal investigators who were awarded a gastrointestinal oncology related R01 grant were included in this study. The H-index consistently showcases a positive correlation with the amount of grant funding, reaching statistical significance in 2020 (H-index coefficient=1510.49, p value=0.07). Concurrently, t-tests emphasize the importance of H-index, illustrating that PI’s with high H-indexes (H-index >42) secure significantly higher funding (average grant=$423,806, p=0.006 compared to those in the lower H-index group (average grant=$420,306, p=0.004). Conversely, citations showcased mixed results, with 2020 revealing a significant negative correlation (coefficient: -1.63, p= 0.04). Publications displayed a strong positive effect in 2021 (coefficient: 231.68, p value=0.10). Seniority exhibited varying impacts across years, notably a significant negative relationship in 2018 (coefficient: -3013.9, p=0.025). Conclusions: This study illuminates the complex interplay between PI’s bibliometric attributes and NIH grant funding outcomes. Notably, high h-index values consistently correlate with a higher funding amount for NIH grants. Although these insights contribute to a deeper understanding of the factors influencing NIH grants, further analysis should investigate additional variables that may significantly impact NIH grant funding.
AI in oncology: Resident perspectives by gender and tech literacy.
Authors: Malucelli Favorito Fernanda , Collie Laura , Kennedy Thomas , Nabhen Jacqueline J. , Safavi Amir , Cerri Giovanni G , Ynoe de Moraes Fabio
Published: June 2024

9055

Background: The integration of AI and ML in oncology demands that physicians adapt and grasp the basics for responsible use. We evaluated AI knowledge and perspectives among Canadian oncology residents, noting differences by program, gender, and tech literacy, and pinpointing education gaps. Methods: An ethics-approved survey collected anonymous responses from Canadian oncology residents, analyzing gender, program, and tech skills. Descriptive statistics, cross-tabs, and chi-square tests assessed associations; t-tests and Mann-Whitney tests compared groups. Results: A total of 57 (31%) residents and fellows, out of an estimated 182, participated, with representation from each oncology training program in Canada. Most of participants were male (63.2%) and most participants self-identified as white (42.1%) or Asian (22.8%). RO programs were better represented than MO programs (68.5% vs 31.6%) with balanced representation across all years of training. In our survey, women equally favored Medical Oncology (MO) and Radiation Oncology (RO) at 50%, but were more in MO (55.6%) than RO (26.3%). Men preferred RO (77.8%) over MO (22.2%). Tech literacy showed a gender gap, with more men (91.7%) feeling tech-savvy than women (8.3%). Tech-savvy respondents leaned towards RO (84%) and were younger (30 vs 33 years). They also showed more willingness to use AI, with a significant difference in willingness scores (1.52 vs 2.06). Despite gender not influencing AI attitudes significantly, tech literacy correlated with better AI understanding. High awareness of AI in medicine was reported (91.2%), with a strong belief in AI's future prevalence (96%). The majority were willing to use AI (86%) and recognized the need to understand it (74%). RO participants were more inclined towards AI education and usage than MO counterparts. The study highlighted a significant interest in AI learning (73%), with a preference for workshops (79%). Only 29% could describe AI, indicating a gap in AI education, despite 63% acknowledging its importance in training. Formal AI training was rare (12.3%), with a desire for more education, especially among RO residents. All findings had p<0.05. Conclusions: Canadian oncology residents anticipate AI's growing influence in medicine but face educational deficiencies. Gender, program preference, and tech literacy impact attitudes toward AI, highlighting the need for inclusive education to bridge gaps and foster diversity in AI's medical application.
Serum Concentrations of Inhibin B in Healthy Females and Males Throughout Life
Authors: Borelli-Kjær Anna , Aksglaede Lise , Jensen Rikke Beck , Hagen Casper Petri , Ljubicic Marie Lindhardt , Busch Alexander Siegfried , Upners Emmie Nicolina , Fischer Margit Bistrup , Jensen Tina Kold , Linneberg Allan , Kårhus Line Lund , Andersson Anna-Maria , Petersen Jørgen Holm , Juul Anders , Johannsen Trine Holm
Published: June 2024

Objective

To describe the natural history of inhibin B throughout life according to sex, age, and pubertal development.

Methods

Based on serum samples from 2707 healthy controls aged 0 to 80 years, sex- and age-specific reference ranges of inhibin B concentrations were constructed. Concentrations were evaluated according to pubertal development and use of oral contraceptives (OCs). Also, measurements from 42 patients with Klinefelter syndrome were included.

Results

In both sexes, inhibin B concentrations were high during minipuberty, decreased in childhood, and significantly increased from Tanner stages B1 to B3 (peak: B4) in females and from G1 to G3 (peak: G3) in males. Despite variations in menstruating females, inhibin B concentrations remained relatively constant after puberty until becoming unmeasurable at menopause. Despite a modest decrease, the inhibin B concentration in males remained relatively high from puberty onward. At any age, males had highest concentrations. Inhibin B SD scores were lower in OC users (median SD score = −0.88) than in nonusers (SD score = 0.35), P < .001. In patients with Klinefelter syndrome, inhibin B concentrations spanned the reference range until approximately 15 years of age, where they decreased to subnormal or unmeasurable levels.

Conclusion

Valuable sex- and age-specific reference data for inhibin B concentrations were provided. In OC users, decreased concentrations of inhibin B underlined the ovaries as the only place of inhibin B production. In patients with Klinefelter syndrome, the decline in inhibin B concentrations at puberty underlined the shift in regulation of inhibin B production at pubertal onset.
Association Between Systemic Immune Inflammation Index and Diabetes Mellitus in the NHANES 2003-2018 Population
Authors: Yan Yufeng , Lu Hongjing , Zheng Yaguo , Lin Song
Published: June 2024

Objects

This study aimed to explore the association between the Systemic Immune-Inflammation Index (SII) and diabetes mellitus (DM) and to assess its influence on the prognosis of the DM and no-DM groups.

Methods

The study used data from the National Health and Nutrition Examination Survey; 9643 participants were included. Logistic regression analysis was employed to evaluate connections between SII and DM. We used the Cox proportional hazards model, restricted cubic spline, and Kaplan–Meier curve to analyze the relationship between SII and mortality.

Results

The logistic regression analysis indicated that a significant increase in the likelihood of developing DM with higher SII levels (odds ratio, 1.31; 95% CI, 1.09-1.57, P = .003). The Cox model showed that there is a positive association between increased SII and higher all-cause mortality. The hazard ratios for SII were 1.53 (1.31, 1.78), 1.61 (1.31, 1.98), and 1.41 (1.12, 1.78) in the total, DM and non-DM groups, respectively. We observed a linear correlation between SII and all-cause mortality in DM participants, whereas non-DM participants and the total population showed a nonlinear correlation.

Conclusion

Elevated SII levels are linked to an augmented risk of DM. Those with DM and higher SII levels demonstrated an elevated risk of mortality.
Activated History: The Case of the Turkish Sieges of Vienna
Authors: Ochsner Christian , Roesel Felix
Published: June 2024

We show that history stored in collective memories and activated by political campaigns can create xenophobia and radicalization. Turkish troops besieged Vienna in 1529 and 1683 and pillaged individual Austrian villages, killing and kidnapping in the process. Attacked places remember those events well but never expressed aversion to Muslims until far-right populists started to campaign against Turks and Muslims in the mid-2000s. We find anti-Muslim sentiments and far-right voting surge in previously attacked places after the populist campaigns were launched, and Turkish communities decrease in response. Historical narratives in political campaigns can mobilize both beliefs and actions. (JEL D72, D83, J15, N43, Z12, Z13)
Patient versus Provider Incentives in Long-Term Care
Authors: Hackmann Martin B. , Pohl R. Vincent , Ziebarth Nicolas R.
Published: June 2024

How do patient and provider incentives affect the provision of long-term care? Our analysis of 551,000 nursing home stays yields three main insights. First, due to limited cost-sharing, Medicaid-covered residents prolong their nursing home stays instead of transitioning to community-based care. Second, when facility capacity binds, nursing homes shorten Medicaid stays to admit more profitable out-of-pocket private payers. Third, providers react more elastically to financial incentives than patients. Thus, targeting provider incentives through alternative payment models, such as episode-based reimbursement, is more effective than increasing patient cost sharing in facilitating transitions to community-based care and generating long-term care savings. (JEL H51, H75, I11, I13, I18, I38, L84)
Spillovers without Social Interactions in Urban Sanitation
Authors: Deutschmann Joshua W. , Lipscomb Molly , Schechter Laura , Zhu Jessica
Published: June 2024

We run a randomized controlled trial coupled with lab-in-the-field social network experiments in urban Dakar. Decision spillovers and health externalities play a large role in determining uptake of sanitation technology, with decision spillovers being largest among households that don’t receive significant subsidies. There is no evidence that the spillovers are explained by social forces in general, nor by specific social mechanisms such as learning from others, social pressure, or reciprocity. We do find evidence of a fourth, nonsocial, mechanism impacting decisions: increasing health benefits. As more neighbors adopt the sanitary technology, it becomes more worthwhile for other households to adopt as well. (JEL I12, O12, O13, O18, Q53, Q55, Z13)
Civil Service Exams and Organizational Performance: Evidence from the Pendleton Act
Authors: Moreira Diana , Pérez Santiago
Published: June 2024

We use newly digitized data to study the impacts of a historical reform that mandated exams for some employees in the largest US customs-collection districts. Although the reform improved targeted employees’ professional backgrounds and reduced turnover, it did not lead to significant improvements in the cost-effectiveness of customs revenue collection. The incomplete reach of the reform was key for this partial success. First, the reform incentivized hiring in exam-exempted positions, distorting districts’ hierarchical structure. Second, since we find suggestive evidence that districts’ top managers mattered for performance, not changing their appointment method might have constituted a missed opportunity for improvement. (JEL D23, D73, H83, J45, N31, N41)
Socioeconomic Disparities in Privatized Pollution Remediation: Evidence from Toxic Chemical Spills
Authors: Marion Justin , West Jeremy
Published: June 2024

Governments often privatize the administration of regulations to third-party specialists paid for by the regulated parties. We study how the resulting conflict of interest can have unintended consequences for the distributional impacts of regulation. In Massachusetts, the party responsible for hazardous waste contamination must hire a licensed contractor to quantify the environmental severity. We find that contractors’ evaluations favor their clients, exhibiting substantial score bunching just below thresholds that determine government oversight of the remediation. Client favoritism is more pronounced in socioeconomically disadvantaged neighborhoods and is associated with inferior remediation quality, highlighting a novel channel for inequities in pollution exposure. (JEL D63, J15, K32, L51, Q53, R23)
Δεκαετής παρακολούθηση ασθενών με αυξημένα επίπεδα λιποπρωτεΐνης (α)
Authors: Χουρσαλάς Αθανάσιος
Published: June 2024

Η λιποπρωτεΐνη (α) [(Lp(α)] είναι χαμηλής πυκνότητας λιποπρωτεΐνη που περιέχει χοληστερόλη. Τα αυξημένα επίπεδα Lp(α) έχουν συσχετιστεί με αθηροσκληρωτική καρδιαγγειακή νόσο, ισχαιμικό αγγειακό εγκεφαλικό επεισόδιο και ασβεστοποιό αορτική στένωση. Θεωρείται επίσης ισχυρός δείκτης υποτροπής καρδιαγγειακών επεισοδίων. Οι εξελίξεις στην κλινική και γενετική έρευνα υποστηρίζουν τον κρίσιμο ρόλο της Lp(α) στην παθογένεια των καρδιαγγειακών νοσημάτων. Στόχοι: Ο σκοπός αυτής της μελέτης ήταν να εξετάσει τη σχέση μεταξύ των επιπέδων Lp(α) και της νοσηρότητας σε ασθενείς με στεφανιαία νόσο. Διερευνήθηκε επίσης ο ρόλος της Lp(α) ως παράγοντα κινδύνου για καρδιαγγειακές εκβάσεις. Υλικό και μέθοδοι: Πρόκειται για μια αναδρομική μελέτη κοορτής. Η ομάδα περιλαμβάνει ασθενείς με στεφανιαία νόσο και συγγενείς ασθενών με στεφανιαία νόσο, οι οποίοι παρακολουθήθηκαν ως εξωτερικοί ασθενείς σε ειδικό ιατρείο λιπιδίων του Ωνασείου Καρδιοχειρουργικού Κέντρου. Η Lp(α) προσδιορίστηκε σε ολόκληρο τον πληθυσμό της μελέτης. Αποτελέσματα: Το δείγμα της μελέτης αποτελούνταν από 860 ασθενείς. Η περίοδος παρακολούθησης κυμαινόταν μεταξύ 8-12 ετών στο 93% του πληθυσμού που εξετάστηκε. Ο κύριος λόγος για παραπομπή στο ιατρείο ήταν η στεφανιαία νόσος, το οικογενειακό ιστορικό στεφανιαίας νόσου και τα αυξημένα επίπεδα λιπιδίων. Συνολικά, η Lp(α) μειώθηκε σημαντικά με την πάροδο του χρόνου (p <0,001). Επιπλέον, τόσο οι πρώτες όσο και οι δεύτερες μετρήσεις Lp(α) συσχετίστηκαν αντιστρόφως με τον Δείκτη Μάζας Σώματος (ΔΜΣ) (p = 0,022 και p = 0,04, αντίστοιχα). Η βασική μέτρηση της Lp(α) ήταν σημαντικά υψηλότερη στην υποομάδα των ασθενών που υποβλήθηκαν σε διαδερμική αγγειοπλαστική των στεφανιαίων αγγείων (PTCΑ) , ενώ παρόμοια τάση παρατηρήθηκε στην δεύτερη μέτρηση Lp(α). Περαιτέρω ανάλυση των δεδομένων έδειξε ότι η Lp(α) μπορεί να χρησιμοποιηθεί ως δείκτης ανίχνευσης των ασθενών που χρειάζονται PTCΑ. Συζήτηση: Η νοσηρότητα αυξάνεται με την πάροδο του χρόνου σε μια μεγάλη ομάδα ασθενών με καρδιαγγειακή νόσο. Η Lp(α) σχετίζεται με το προφίλ λιπιδίων, τον ΔΜΣ και άλλους βιοχημικούς δείκτες. Η Lp(α) είναι ένας δείκτης που δυνητικά μπορεί να προδικάσει την ανάγκη για διενέργεια PTCΑ.
Bringing ‘Such Matters Upon the Stage’: Women Exemplars in A Warning for Fair Women (1599) and Golding’s A Briefe Discourse (1573)
Authors: Christensen Ann
Published: June 2024

This essay argues that the unnamed playwright of the 1599 tragedy A Warning for Fair Women adapts Arthur Golding’s 1573 (rpt 1577) pamphlet to reshape the heroine from a negative example of adultery and the beneficiary of church-induced repentance into a positive model of motherhood and spiritual agency aided by another woman. Missing from Golding’s account, the play’s main source and the fount of subsequent reportage on the murder of George Sanders, is attention to women’s spiritual agency and their friendship. I compare the play and source text to argue that the playwright’s emendations of Golding’s material omit or minimize certain elements, including the moralizing tone, to advance a more positive view of women than critics have recognized.
The Queen in Shakespeare’s Q1 Hamlet
Authors: Held Joshua
Published: June 2024

Although long maligned, the 1603 first quarto of Shakespeare’s Hamlet (Q1) portrays a strong queen and mother figure in Gertred, specifically in a scene that is unique to this version of the play. While some grant that Gertred may be a more sympathetic character than her counterpart Gertrard in the second quarto (Q2) or Gertrude in the Folio (F), critics generally neglect the Q1-only scene involving her and Horatio, finding it repetitious and dull. This essay’s close reading of this scene shows that Gertred excels at diplomatic intrigue, building strategic alliances through a distinctive politics of motherhood.
Co mruczy w Obcym? Egzystencjalne i postkolonialne czytanie Camusa
Authors: Kałuża Maciej
Published: June 2024

Reading of Camus Państwowy Instytut Wydawniczy has recently published a new translation of Outsider, enriched with a wonderful and extensive afterword written by Marek Bieńczyk. One of the themes analysed there is the problem of colonialism and the way in which the plot of Camus’s novel relates to the racial, ethnic and cultural prejudices of the colonists. In opposition to the proposal that Camus’s democratic views in the analysis of this thread should be bracketed out, my text is an appeal that in the case of examining Camus’s work, brackets should not be applied.
Managerial and Financial Barriers to the Green Transition
Authors: De Haas Ralph , Martin Ralf , Muûls Mirabelle , Schweiger Helena
Published: June 2024

Using data on 10,776 firms across 22 emerging markets, we show that both credit constraints and weak green management hold back corporate investment in green technologies embodied in new machinery, equipment, and vehicles. In contrast, investment in measures to explicitly reduce emissions and other pollution is mainly determined by the quality of a firm’s green management and less so by binding credit constraints. Data from the European Pollutant Release and Transfer Register reveal the environmental impact of these organizational constraints. In areas where more firms are credit constrained and weakly managed, industrial facilities systematically emit more CO2 and pollutants. A counterfactual analysis shows that credit constraints and weak management have respectively kept CO2 emissions 4.5% and 2.3% above the levels that would have prevailed without such constraints. This is further corroborated by our finding that in localities where banks had to deleverage more due to the global financial crisis, carbon emissions by industrial facilities remained 5.6% higher a decade later.

This paper was accepted by Lukas Schmid, finance.

Supplemental Material: The online appendices and data files are available at https://doi.org/10.1287/mnsc.2023.00772 .
A surgical approach the rabbit patient: part 2
Authors: Miles Sonya
Published: June 2024

When performing any rabbit surgery, understanding the unique anatomical and physiological differences between rabbits and more frequently seen mammalian patients is essential. This article continues to take the reader through various surgical procedures that are performed in rabbits, including thoracic, abdominal, endoscopic and orthopaedic surgeries. The specifics of rabbit postoperative care are also discussed. The essential techniques discussed in the first part of this series of articles are also relevant to the second part.
Plot Scale Evaluation of the Hydrologic and Water Quality Benefits of Blue Roofs Compared to Green and Conventional Roofs
Authors: Waickowski Sarah E. , DeGaetano Shane , Anderson Andrew , Amatya Devendra M. , Hunt William
Published: June 2024

Highlights

There were no significant differences (a = 0.05) in rainfall retention between blue and green roofs.

Blue roofs appear to be a viable option to green roofs when the priority is stormwater management.

Blue and green roofs need to be studied on larger scales to gain more confidence in the treatment provided.

Abstract. Impervious surfaces caused by urbanization alter hydrologic conditions. In ultra-urban areas (75% or more impervious), rooftop stormwater control measures (SCMs), such as green roofs, exploit underutilized rooftop space. Green roofs reliably attenuate rainwater, but associated water quality treatment results are not as consistent. This study explored the viability of blue roofs, an emerging technology, as an alternative to green roofs. Nine adjacent plots consisting of three each of conventional (control), green, and blue roofs were constructed in Raleigh, NC. As a part of hydrology monitoring, on-site rainfall was measured using a tipping bucket and verified using a manual gauge. Water quantity data were collected using water level loggers in storage bins placed under the roof plots to record outflow. Measured rainfall retention was similar for blue and green roofs, and both systems were significantly (a = 0.05) and substantially (50%) more retentive than control roofs. A comparison of evaporation rates suggested blue roofs may be more effective at regenerating storage capacity than green roofs. Thirteen water quality events were sampled, and the mean total nitrogen (TN) concentration from the green and blue roofs was 5.83 and 2.18 mg/L, respectively. Similarly, the mean total phosphorus (TP) concentration from the green and blue roofs was 2.75 and 0.25 mg/L, respectively. Total suspended solids (TSS) data were collected, but seven of 13 samples were below the practical quantitation limit (2.5 mg/L), and the data were not statistically analyzed. Total kjeldahl nitrogen (TKN), TP, and orthophosphate (O-PO4
3-) concentrations from green roof treatments were significantly (a = 0.05) larger than concentrations from blue roofs. Except for nitrate/nitrite nitrogen (NO2,3-N), there were no significant differences between blue and control roof pollutant concentrations. However, green roofs often discharged substantially higher pollutant loads than control roofs for every pollutant other than NO2,3-N and total ammonical nitrogen (NH3-N). While blue roofs may lack the aesthetic appeal of green roofs, this study suggests blue roofs are a relatively cost-effective option, likely preferable, when solely focused on the benefits of stormwater management from rooftops. Keywords: Blue roofs, Conventional roofs, Green roofs, Hydrology, Monitoring, Stormwater control measures, Water quality.
Allah’s House to Domes of Secularism: Minoritization of Muslims in India
Authors: Kiliyamannil Thahir Jamal
Published: June 2024

Disputes around the Babri masjid have been crucial for understanding the Muslim subject position in India, also because mosques are public expressions of Muslimness. I read the legal proceedings of the Babri masjid dispute leading to the Supreme Court’s controversial judgment in 2019, tracing the life of Babri masjid unfolding as a mosque, a disputed site and, finally, a Hindu temple. Focusing on the theological and secular claims of Hindu and Muslim litigants, I look at the differential approach to belief and historical claims within the legal adjudication. I especially analyse two strategies, disruption and description, that significantly led to the changes in the attributes of the mosque.

Comparing the Babri dispute with the case of the Malappuram mosque dispute in the eighteenth century, this article analyses theological claims on a mosque, asking the question why the Muslim narrative shifted from one rooted in religious reverence, Allah’s house, to one anchored in secular symbolism, the domes of secularism? It would discreetly give an idea of the practice of secularism in India which, as different scholars contend, systematically erases Muslim religiosity from the public space. I suggest reading the anchoring of Muslim claims in secularism as pointing to the crucial changes in the Muslim subject position that is decisively framed through excessive powers of the modern nation-state.
Why Democratize Psychiatric Research?
Authors: Friesen Phoebe
Published: June 2024

Abstract: Building on decades of rich discussions of why 'nothing about us without us' matters in the field of psychiatry, this paper aims to illuminate the justifications underlying participatory research in psychiatry, and how these justifications might shape participatory methodologies. This is accomplished through the examination of several epistemic and ethical features of psychiatry that underlie the importance of engaging in participatory research in the field, unpacking their connection to participatory research, and offering suggestions related to their implications for research methodologies. The epistemic features include: the irreducible value of patient experience, the extent of disagreement and uncertainty in the field, and the value-laden nature of knowledge in psychiatry. The ethical features include: the preponderance of harm, denials of agency and epistemic injustice, and the constant struggle for power. These features offer useful touchpoints for thinking through why participation matters in mental health research.
MIMO optical communication systems based on broadband transmitters and receivers
Authors: Yang Tao , Wu Hao , Zhang Yue , Wang Xu , Zhou Xinhui , Niu Qiaoli , Zeng Wenjin , Shen Xiao
Published: June 2024

A multiple-input multiple-output (MIMO) optical communication system is proposed. In the MIMO optical communication system, a series of broadband sources with different spectra act as the transmitters, and a compact imaging chip sensor accompanied by a disorder dispersion component and a calculating component serve as the receivers. Because the spectral ranges of the sources are overlapped, the number of the signal channels is not restricted by the bandwidth of the communication band and the characteristics of the sources. L1-norm regularization, L2-norm regularization, and the simulated annealing algorithms are used to solve matrix equations for decoding the signals at the receivers. A proof-of-concept experiment using on-off keying modulation has been done to prove the feasibility of the design. The experimental results demonstrate that the signals decoded by the receivers fit well with those generated from the transmitters. Besides the function of communications, the broadband sources are suitable to act as illumination sources because the white color lights in the visible band are more comfortable for human eyes compared with monochromatic lights used in traditional visible light communication (VLC) systems. We also prove that the MIMO optical communication system can operate in the infrared band. The infrared communication (IC) system has potential applications in situations requiring communication in a dark environment that cannot be realized by VLC systems.
Optoelectronic nonlinear Softmax operator based on diffractive neural networks
Authors: Zhan Ziyu , Wang Hao , Liu Qiang , Fu Xing
Published: June 2024

Softmax, a pervasive nonlinear operation, plays a pivotal role in numerous statistics and deep learning (DL) models such as ChatGPT. To compute it is expensive especially for at-scale models. Several software and hardware speed-up strategies are proposed but still suffer from low efficiency, poor scalability. Here we propose a photonic-computing solution including massive programmable neurons that is capable to execute such operation in an accurate, computation-efficient, robust and scalable manner. Experimental results show our diffraction-based computing system exhibits salient generalization ability in diverse artificial and real-world tasks (mean square error <10−5). We further analyze its performances against several realistic restricted factors. Such flexible system not only contributes to optimizing Softmax operation mechanism but may provide an inspiration of manufacturing a plug-and-play module for general optoelectronic accelerators.
Remittance from migrants reinforces forest recovery for China’s reforestation policy
Authors: Zhang Qi , Tao Shiqi , Jagger Pamela , Band Lawrence E. , Bilsborrow Richard E. , Zhang Zhiqiang , Huang Qingfeng , Zhang Quanfa , Moody Aaron , Song Conghe
Published: June 2024

Forests play a key role in the mitigation of global warming and provide many other vital ecosystem goods and services. However, as forest continues to vanish at an alarming rate from the surface of the planet, the world desperately needs knowledge on what contributes to forest preservation and restoration. Migration, a hallmark of globalization, is widely recognized as a main driver of forest recovery and poverty alleviation. Here, we show that remittance from migrants reinforces forest recovery that would otherwise be unlikely with mere migration, realizing the additionality of payments for ecosystem services for China’s largest reforestation policy, the Conversion of Cropland to Forest Program (CCFP). Guided by the framework that integrates telecoupling and coupled natural and human systems, we investigate forest-livelihood dynamics under the CCFP through the lens of rural out-migration and remittance using both satellite remote sensing imagery and household survey data in two representative sites of rural China. Results show that payments from the CCFP significantly increases the probability of sending remittance by out-migrants to their origin households. We observe substantial forest regeneration and greening surrounding households receiving remittance but forest decline and browning in proximity to households with migrants but not receiving remittance, as measured by forest coverage and the Enhanced Vegetation Index derived from space-borne remotely sensed data. The primary mechanism is that remittance reduces the reliance of households on natural capital from forests, particularly fuelwood, allowing forests near the households to recover. The shares of the estimated ecological and economic additionality induced by remittance are 2.0% (1.4%∼3.8%) and 9.7% (5.0%∼15.2%), respectively, to the baseline of the reforested areas enrolled in CCFP and the payments received by the participating households. Remittance-facilitated forest regeneration amounts to 12.7% (6.0%∼18.0%) of the total new forest gained during the 2003–2013 in China. Our results demonstrate that remittance constitutes a telecoupling mechanism between rural areas and cities over long distances, influencing the local social-ecological gains that the forest policy intended to stimulate. Thus, supporting remittance-sending migrants in cities can be an effective global warming mitigation strategy.
The strength of balance: Strength and dynamic balance in children with and without hypermobility
Authors: Ituen Oluwakemi A. , Duysens Jacques , Ferguson Gillian , Smits-Engelsman Bouwien
Published: June 2024

Background

Generalized Joint hypermobility (GJH) is predominantly non-symptomatic. In fact, individuals with joint flexibility usually perform better than their non-hypermobile counterparts during physical activities. Notwithstanding, strength and balance are essential to maintain the control of the extra range of motion during activities and to prevent musculoskeletal complications. There are limited and conflicting pieces of evidence in literature regarding the association between strength and balance in children with GJH.

Objectives

The purpose of this study was to examine differences in functional strength, dynamic balance, proprioception, and isometric strength in children with and without joint hypermobility and determine the association between strength outcomes and dynamic balance.

Method

A cross-sectional study was conducted among children aged 6 to 11. Hypermobility was determined using the Beighton Score, with scores ≥6 representing hypermobility. Functional strength was assessed with the Functional Strength Measure (FSM), isometric strength was determined with a handheld dynamometer (HHD), the Y-Balance Test (YBT) was used to assess dynamic balance and the Wedges test to measure proprioception.

Results

This study included 588 participants (age: 7.97 ± 1.3 years; height: 128±10.1 cm; mass: 27.18 ± 7.98 kg). 402 children were classified as having normal mobility and 186 as being hypermobile. Hypermobile children had better functional strength in the lower extremities than children with normal range mobility but lower reach distance in the YBT. No differences in proprioception, functional strength of the upper extremity or isometric strength in the hands were found. However, isometric lower extremity force was less in hypermobile children than children with normal range mobility. Irrespective of their joint mobility, a fair significant correlation existed between total Y-balance distance and FSM items r = 0.16–0.37, p = 0.01. Correlations between total Y-balance distance and isometric strength of knee and ankle muscles ranged between r = 0.26–0.42, p = 0.001.

Conclusion

Hypermobile joints seem to co-occur with lower extremity isometric strength, more functional strength in the lower extremities and less reaching distance in dynamic balance. The opposing direction of the results on functional and isometric strength tests highlights the importance of the type of outcome measures used to describe the association of strength and the range of motion.