bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-world treatment patterns and outcomes in patients with myelofibrosis treated with pacritinib in the United States.
Authors: Marrone Michael , Geller Robert , Oladapo Abiola , Suthar Purvi , Vasudevan Anupama , Vredenburg Michael , Zeng Jia , Rampal Raajit , Mascarenhas John
Published: June 2024

6579

Background: Pacritinib (PAC), a JAK1 sparing JAK2/IRAK1/ACVR1 inhibitor, has shown clinically significant activity in spleen volume and symptom reduction in patients (pts) with thrombocytopenic myelofibrosis (MF). Thrombocytopenic MF is challenging to manage and pts with platelets (PLT) <50 x109/L have limited median overall survival (OS) of 15 months (mo) (Masarova 2018). Since approval as the only agent for thrombocytopenic MF, real-world evidence of PAC use is limited. This study aims to assess treatment patterns, hematological outcomes, and survival in pts with MF treated with PAC in the US. Methods: For this retrospective study, Integra-PrecisionQ de-identified database was used to locate pts with MF (ICD-10: 75.81, D47.4) treated with PAC from 6/1/2022 to 8/31/2023. Treatment-related outcomes include PLT and hemoglobin (Hb) levels from PAC initiation (index) and 30-day intervals post-index. OS was assessed from index through the end of the study period. Data are presented as medians and interquartile ranges (IQR). Results: 142 pts with MF were treated with PAC, the majority being male (60%) or White (66%), with a median age at MF diagnosis of 72 years and median of 13.4 mo from diagnosis to index. In pts receiving ≥2nd line (2L) PAC (65.5%), the median time from the end of prior MF therapy to PAC initiation was 1 day. Median follow up from index was 6 mo and median exposure to PAC during the observation period was 5.3 mo. In pts with PLT and Hb levels at index and follow up, 28.5% (34/119) had severe thrombocytopenia (PLT<50 x109/L) at index and 29% (35/119) had severe anemia (Hb <8.0 g/dL). Median PLT count was 81 x109/L (47.5,179) at index (n=119) and 96 x109/L (68.5,125) at post-index day 360 (n=15). Median Hb level was 8.8 g/dL (7.9,10.3) at index (n=119) and 10.4g/dL (9.2,11.6) at post-index day 360 (n=15). Increases in PLT and Hb were observed across index PLT and Hb groups over follow up (Table 1). 1-year OS probability was 69.4% (95% CI=56.8-79.0) overall, 77.3% (95% CI=61.5-87.3) in pts treated with 1L PAC, and 75.2% (95% CI=46.3-90.0) for pts treated with 1L PAC with PLT <50 x109/L. Conclusions: In addition to spleen and symptom benefits, real-world outcomes demonstrate stability or improvement in thrombocytopenia and anemia in MF pts treated with PAC, with OS in the 1L setting comparing favorably with other JAK inhibitor historical controls. [Table: see text]
Lisocabtagene maraleucel (liso-cel) vs standard of care (SOC) with salvage chemotherapy (CT) followed by autologous stem cell transplantation (ASCT) as second-line (2L) treatment in patients (pt) with R/R large B-cell lymphoma (LBCL): 3-year follow-up (FU) from the randomized, phase 3 TRANSFORM study.
Authors: Kamdar Manali Kirtikumar , Solomon Scott R. , Arnason Jon , Johnston Patrick B. , Glaß Bertram , Bachanova Veronika , Ibrahimi Sami , Mielke Stephan , Mutsaers Pim , Hernandez-Ilizaliturri Francisco J. , Izutsu Koji , Morschhauser Franck , Lunning Matthew Alexander , Chow Victor A. , Santamaria Josu , Colicino Silvia , Ogasawara Ken , Stepan Lara , Abramson Jeremy S.
Published: June 2024

7013

Background: Liso-cel is an autologous, CD19-directed, 4-1BB CAR T cell product. In prespecified interim and primary analyses of TRANSFORM (NCT03575351), liso-cel showed significant improvements in efficacy vs SOC in pts with R/R LBCL. Here we report results after ~3-y FU. Methods: TRANSFORM is a randomized phase 3 study comparing liso-cel vs SOC (CT [R-DHAP, R-ICE, or R-GDP] then high-dose CT [HDCT] + ASCT) in adults aged ≤ 75 y with LBCL primary refractory to or relapsed ≤ 12 mo after first-line therapy and eligible for ASCT. Liso-cel arm pts underwent lymphodepletion followed by liso-cel (100 × 106 CAR+ T cells). Bridging therapy was allowed. SOC arm pts received 3 cycles of CT; responding pts proceeded to HDCT + ASCT. Crossover to receive liso-cel was allowed for SOC arm pts if criteria were met. The primary endpoint was event-free survival (EFS) per independent review committee (IRC). Key secondary endpoints included CR rate and PFS per IRC, and OS. Endpoints were not statistically retested and are reported descriptively. Results: In total, 184 pts were randomized (92 per arm); baseline characteristics were reported (Abramson et al. Blood 2023). Median (range) FU was 33.9 mo (0.9–53.0). Median EFS, PFS, and duration of response (DOR) were longer for liso-cel vs SOC, similar to the primary analysis (Table). A total of 61 (66%) SOC arm pts crossed over to receive liso-cel. Median OS was not reached (NR) in either arm; 36-mo OS rates were numerically higher for liso-cel. Of 76 total deaths (liso-cel, n = 34; SOC, n = 42 [crossover pts, n = 33]), 10 occurred since the primary analysis (liso-cel, n = 6; SOC, n = 4 [all crossover pts]); most were due to disease progression or complications (n = 6). Safety results were consistent with the primary analysis. Cellular kinetics and B-cell aplasia will be presented. Conclusions: After median FU of 33.9 mo, liso-cel as 2L treatment in pts with primary refractory or early relapsed LBCL resulted in deepening of response and continued improvement in efficacy endpoints over SOC, confirming the ongoing benefit of liso-cel. Clinical trial information: NCT03575351 . [Table: see text]
Cost analysis of targeted and immunotherapies in operable esophageal and non-small cell lung cancers.
Authors: Alwatari Yahya , Shanshal Mohamed , Johnson Nate C , Thao Viengneesee , Borah Bijan J. , Shen Robert
Published: June 2024

8051

Background: The National Comprehensive Cancer Network (NCCN) currently recommends the use of Atezolizumab, Nivolumab, Osimertinib, and Pembrolizumab in the perioperative management of non-small cell lung cancers (NSCLC) and esophageal cancers (EC). As the therapeutic landscape evolves, we aim to evaluate the cost implications of these guidelines for eligible patients in the United States. Methods: The Medicare Part B payment allowance limits of each medication were ascertained except Osimertinib for which an approximate wholesale acquisition cost (WAC) was reported due to privately administered Medicare Part D coverage. Using national data and published literature, we estimated the annual incidence of patients with newly diagnosed EC and NSCLC who would be eligible for surgery combined with neoadjuvant and/or adjuvant immune and targeted therapy. We applied the estimated cost of the medication based on dosing and duration of treatment, which spanned 1 year for all but adjuvant Osimertinib, which spanned 3 years. Using these data, the cost per patient and the total cost for an incident cohort were estimated. Results: We estimated that 8,602 patients with newly diagnosed EC would be eligible for adjuvant Nivolumab; the cost to treat one patient was $248,529, and the cost to treat one incident cohort was approximately $2 billion (Table). We estimated that 50,409 patients with NSCLC will meet the criteria for neoadjuvant Nivolumab with a total cost of three cycles of $32,894 per patient and $1.7 billion per cohort. Among NSCLC patients who may undergo resection and qualify for adjuvant therapy (Stage IB – IIA with high-risk features or IIB-IIIA), 85,063 patients are anticipated to be EGFR-negative and treated with adjuvant Atezolizumab or Pembrolizumab. Treatment costs range from $178,584 – $197,320 per patient with up to $16 billion cost per cohort. The cost to treat one patient with adjuvant Osimertinib was $556,720, and the cost to treat one incident cohort was close to $10 billion. In total, the cost to treat an incident cohort of eligible operable thoracic malignancies could exceed $30 billion. Conclusions: Neoadjuvant and adjuvant immune and targeted therapy in operable thoracic patients is associated with a significant cost burden. Prospective large-scale studies are needed to assess cost-effectiveness, particularly given the paucity of superior overall survival data with these agents. [Table: see text]
Four-year outcomes and circulating tumor DNA (ctDNA) analysis of pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in unresectable, locally advanced, stage III non–small-cell lung cancer (NSCLC): From KEYNOTE-799.
Authors: Reck Martin , Lee Ki Hyeong , Frost Nikolaj , Breder Valeriy Vladimirovich , Kowalski Dariusz M. , Levchenko Evgeny , Reguart Noemi , Martinez-Marti Alex , Houghton Baerin , Paoli Jean-Baptiste , Safina Sufiia , Liu Hong , Novinskiy Vladimir , Dettman E.J. , Kobie Julie , Jabbour Salma K.
Published: June 2024

8057

Background: The nonrandomized phase 2 KEYNOTE-799 study (NCT03631784) of pembro + cCRT in previously untreated unresectable, locally advanced, stage III NSCLC demonstrated an ORR of 70.5% in cohort A (squamous and nonsquamous) and 70.6% in cohort B (nonsquamous only) after median follow-up of 18.5 mo and 13.7 mo, respectively. We present outcomes with ⁓4 y of follow-up and analysis of ctDNA. Methods: Eligible patients (pts) were aged ≥18 y with unresectable confirmed stage IIIA–C NSCLC (per AJCC v8), measurable disease per RECIST v1.1, and ECOG PS 0 or 1. Pts in cohort A (squamous and nonsquamous) received carboplatin + paclitaxel and pembro 200 mg for one 3-wk cycle, followed by carboplatin + paclitaxel QW for 6 wks + 2 cycles of pembro 200 mg Q3W + standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin, pemetrexed, and pembro 200 mg Q3W + standard TRT in cycles 2 and 3. All pts received 14 additional cycles of pembro. Primary endpoints were ORR per RECIST v1.1 by BICR and incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). As an exploratory endpoint, tumor ctDNA was assessed in available plasma samples collected at baseline and cycle 7 using the Signatera ctDNA assay. Results: Of 214 pts enrolled, including 112 in cohort A and 102 in cohort B. Median (range) time from first dose to database cutoff (Oct 16, 2023) was 54.1 (49.2–59.4) and 49.3 (38.4–59.1) mo, respectively. ORR was 71.4% in cohort A and 74.5% in cohort B (Table). Grade ≥3 pneumonitis (primary endpoint) occurred in 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Grade 3–5 treatment-related AEs occurred in 73 pts (65.2%) in cohort A and 52 (51.0%) in cohort B. Of ~136 samples sent for sequencing, 73 pts (~53.7%) had samples evaluable for ctDNA at baseline. ORR was 68.7% in pts with ctDNA detectable (n = 67) vs 50.0% in pts with ctDNA non-detectable samples (n = 6) at baseline. Among 46 pts with ctDNA detectable at baseline and evaluated at cycle 7, 32 (69.6%) had cleared ctDNA at cycle 7; these pts had better trends in PFS and OS vs pts who had not cleared ctDNA at cycle 7 (n = 14). Conclusions: With ~4 y of follow-up, pembro + cCRT continues to demonstrate durable antitumor activity and manageable safety in previously untreated unresectable, locally advanced stage III NSCLC. ctDNA was evaluable in ~half of the samples assessed; most pts with detectable ctDNA at baseline had cleared ctDNA at cycle 7. Clinical trial information: NCT03631784 . [Table: see text]
Clinical outcomes of maintenance durvalumab after definitive concurrent chemoradiotherapy in unresectable locally advanced stage III non-small cell lung cancer according to epidermal growth factor receptor and anaplastic lymphoma kinase status: Korean Cancer Study Group LU-22-18.
Authors: Choi Dae-Ho , Ahn Myung-Ju , Kim Miso , Kim Young Saing , Park Keon Uk , Cho Jang Ho , Kim Hongsik , Lee Ki Hyeong , Ahn Heejoon , Kim Il-Hwan , Lee Kyung-Hee , Lee Gyeong-Won , YI Seong Yoon , AHN Beung Chul , Lee Min-Young , Jung Hyun Ae , Park Sehhoon , Sun Jong-Mu , Ahn Jin Seok , Lee Se-Hoon
Published: June 2024

8061

Background: The role of maintenance durvalumab after definitive concurrent chemoradiotherapy (CCRT) in unresectable locally advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor ( EGFR) mutation or anaplastic lymphoma kinase ( ALK) translocation remains unclear. We compared the effectiveness of durvalumab maintenance therapy in groups with EGFR/ALK wild-type versus those with EGFRor ALK mutations. Methods: In this retrospective multicenter observational study, patients with locally advanced NSCLC without progression after CCRT followed by maintenance durvalumab and available molecular test results ( EGFR and ALK) were eligible. The primary objective was to compare progression-free survival (PFS) between EGFR/ ALK wild-type and EGFRor ALKmutant NSCLC. Secondary objectives include overall survival according to EGFRor ALK mutation and programmed cell death-ligand 1 (PD-L1) expression. Results: Among 339 patients, 279 had wild-type EGFR/ALK, 41 had EGFR mutations and 19 had ALK translocations. The median age was 68 years with 276 males (81.4%) and 63 females (18.6%), 165 (49.3%) had adenocarcinoma, 149 (44.5%) had squamous cell carcinoma, and 21 (6.3%) had other histological types, 120 (35.4%) had stage IIIA, 168 (49.6%) stage IIIB, and 51 (15.0%) had stage IIIC. The majority of patients (n=288, 85%) achieved partial response to CCRT, 2 (0.6%) had a complete response, and 49 patients (14.4%) had stable disease. Excluding 4 patients with unknown PD-L1 tumor proportion score (TPS), 16 (4.8%) had a PD-L1 TPS of 0, 168 (50.1%) had 1-49, and 151 (45.1%) had 50 or higher. The median PFS was 21.4 months (95% CI 17.3–25.3) for the EGFR/ ALK wild-type group and 21.0 months (95% CI 15.7–NA) for the EGFR or ALK mutant group with no significant difference (p=0.74). Significant differences occurred in PFS based on PD-L1 expression with values of 13.6 (95% CI 10.5–NA), 18.7 (95% CI 15.1–26.9), and 24.7 (95% CI 20.7–NA) months for TPS of 0, 1–49, and 50 or higher, respectively (p=0.02). Conclusions: Durvalumab maintenance therapy after definitive CCRT in unresectable locally advanced NSCLC patients with EGFRor ALK mutation demonstrates comparable clinical outcomes to those with wild-type EGFR/ALK when PD-L1 expression is present.
Comprehensive analysis of the value of dynamic changes in ctDNA in SCLC.
Authors: Joseph Peronne , Chen Zhengyi , Ajay Abhishek , Fu Pingfu , Dowlati Afshin
Published: June 2024

8107

Background: Dynamic changes in circulating tumor DNA (ctDNA) have not been studied in small-cell lung cancer (SCLC). Here, we assessed the changes of ctDNA over time and clinical outcomes. Methods: We performed a 105-gene, hybrid-capture, next-generation sequencing (NGS) liquid biopsy assay that detects SNVs, in/dels, CNVs, and chromosomal rearrangements. Patients had ctDNA assessed at 3 time points: 1) before initiation of front-line therapy; 2) at remission (within 3-6 weeks of 4th cycle of chemotherapy+/- immunotherapy), and 3) at the time of relapse (based on radiographic imaging). Study outcome measures include OS, PFS, DFS (duration of response from completion of 4th cycle of systemic treatment until relapse), and overall response rate (ORR). Survivor distribution was estimated using Kaplan-Meier methods. Cox model was also used to estimate the effects on OS, PFS and DFS. The effects of predictors on ORR were estimated using logistic regression. The T-test was used to examine the difference in continuous measures between the two groups, and the chi-square test was used to examine the association between two categorical factors. All tests were two-sided, and p-values < 0.05 were considered significant. Results: 62 patients were enrolled. The median follow-up was 12.3 mos. Patients were treated with standard-of-care chemotherapy +/- immunotherapy for 4 cycles. 71% had extensive stage disease. At baseline, 100% of patients had detectable variant alleles in TP53,and 70% had variant RB1. Patients with ES-SCLC had significantly higher maximum (max) Variant Allelic Fraction (VAF) (alteration with highest VAF) compared to LS-SCLC (59.1 vs 27.2%, p = 0.04). Median max VAF at baseline was 52.3%, 0.3% at remission, and 38.4% at relapse, indicating a response to therapy. However, ORR did not correlate with baseline max VAF (p = 0.2). Baseline max VAF (comparing those < or > VAF of 45%) was not associated with OS (19.4 vs 12.2 mos, p = 0.6) but highly impacted PFS (11.2 vs. 6.1 mos, p = 0.02) and DFS (12.1 vs 2.2 mos, p = 0.004). Baseline max VAF was an independent predictor of PFS and DFS. A drop in max VAF from pretreatment to remission (comparing those with a > or < 99% decrease) also did not associate with OS, PFS, or DFS. Patients with RB1 alterations at pretreatment that had residual RB1 alterations at the time of clinical remission had significantly worse PFS (6.3 vs 12.1 mos) and DFS (1 vs 8 mos, p = 0.02). Conclusions: Baseline max VAF ctDNA levels strongly correlate with PFS and DFS (duration of remission from completion of 4th cycle of treatment) but not OS and ORR. Most strikingly, those with detectable residual RB1 alterations at completion of proscribed chemotherapy have an extremely short DFS of 1 month that justifies early assessment for clinical trials. This approach has led to a near 90% success rate in enrollment on 2nd line clinical trials or SOC options.
Efficacy and safety of vebreltinib in patients with advanced NSCLC harboring MET exon 14-skipping: Results of 2.5-year follow-up in KUNPENG.
Authors: Yang Jin-Ji , Zhang Yan , Wu Lin , Hu Jie , Wang Zhe-Hai , Chen Jing-Hua , Fan Yun , Lin Gen , Wang Qiming , Yao Yu , Zhao Jun , Chen Yuan , Fang Jian , Song Yong , Zhang Wei , Cheng Ying , Guo Ren-Hua , Li XingYa , Wu Yi-Long
Published: June 2024

8557

Background: Vebreltinib (PLB1001), a potent and highly selective c-MET inhibitor, demonstrated superior objective response rate (ORR) benefits in locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients (pts) with MET exon 14 (METex14) skipping mutations in the previous analysis of the phase II KUPENG study. Here we present results from 2.5 years of follow-up of pts in KUNPENG. Methods: In this Phase Ⅱ, open-label, multicenter, and multi-cohort study, tumor tissue was assessed for METex14 skipping mutation using next-generation sequencing (NGS) from CAP or CLIA certificated local or central laboratories. Pts in Cohort 1 received 200 mg of vebreltinib twice daily (28 days per cycle) until discontinuation criteria were met. The primary endpoint was ORR assessed by blinded independent review committee (BIRC). Results: Between Jan 17, 2020 and Feb 09,2021, 52 pts were enrolled in Cohort 1. As of the data cutoff date (Aug 09, 2023), the median duration of follow-up was 19.1 months (range, 1.0-42.7) and the median duration of treatment was 9.9 months (range, 0.6-42.7). Per BIRC assessment, the ORR was 75% (95% CI: 61.1-86.0), the disease control rate (DCR) was 96.2% (95% CI 86.8-99.5), the median duration of response (DoR) was 16.5 months (95% CI 9.2-19.4), the median time to response (TTR) was 1.0 month (95% CI 1.0-2.8), the median progression-free survival (PFS) was 14.3 months (95% CI 6.4-18.2), and the median overall survival (OS) was 20.3 months (95% CI 16.2-29.7). The 3-year OS rate was 35.1%. Subgroup analyses showed the ORR was 100.0%, 66.7%, 85.7% and 100.0% among pts with any baseline brain metastases (N=5), pts with any baseline liver metastases (N=6), pts aged 75 years and older (N=21) and pts with co-occurring of MET amplification (N=12), respectively. The most common (≥20%) treatment-related adverse events (TRAEs) in all the 135 pts enrolled in this study were peripheral edema (56.3%), hypoalbuminemia (27.4%), hypoproteinemia (25.9%) and anemia (20.7%). TRAEs were mainly grade 1 or 2. No new safety signals were reported with long-term vebreltinib treatment. Conclusions: Vebreltinib consistently showed promising efficacy and favorable safety in NSCLC pts with METex14 mutations. Clinical trial information: NCT04258033 . [Table: see text]
Precision medicine in NSCLC: Challenges and practice gaps in community cancer clinics.
Authors: Sidiropoulos Nikoletta , Brahmer Julie R. , Storey Janet , Dewald Ilona , Dooyema Samuel , Carter Jeffrey D. , Heggen Cherilyn , McKinnon Kelly E.
Published: June 2024

8589

Background: Current guidelines for clinical management of advanced NSCLC recommend testing for nine molecular alterations in addition to PD-L1, to identify appropriate patients for targeted therapies. This quality improvement initiative evaluated current practice patterns in biomarker testing in NSCLC in community oncology clinics. Methods: In 2023, 68 healthcare providers (HCPs) from 6 clinics completed surveys on biomarker testing, treatment decision making, and patient-centered care in NSCLC. Teams from each clinic (N=98) then participated in audit/feedback (AF) sessions to assess site-specific gaps and develop and implement action plans for improvement. Results: Many advanced NSCLC patients did not receive the recommended biomarker tests (Table). This is likely related to low rates of next-generation sequencing (NGS) based testing: only 45% or 30% of patients received DNA-based or RNA-based NGS, respectively. Most HCPs (72%) reported testing at time of diagnosis, and about one-third also tested at time of disease progression. However, 48% of HCPs were very/extremely likely to start treatment before receiving molecular test results, and 49% said that "determining whether to begin treatment prior to receipt of molecular testing results" was their top challenge in NSCLC care. Rates of targeted therapy receipt were low, with 33% of HCPs reporting that fewer than half of their patients with an actionable mutation received the corresponding agent. Providers believed "improved collaboration across interprofessional teams" (24%) and "integration of multidisciplinary tumor boards into treatment planning" (22%) would most improve care for NSCLC patients. To address identified gaps, teams developed action plans, including establishing new workflows to better incorporate molecular testing and designating a team member to facilitate multidisciplinary collaboration. Following the AF session, providers reported high confidence in selecting appropriate biomarker tests (83%) and biomarker-directed therapies (75%) for patients with NSCLC . Full findings will be presented, along with follow-up surveys measuring real-world impact of the system-level practice changes. Conclusions: Although most HCPs used some form of molecular testing in NSCLC, testing was not as comprehensive as current guidelines recommend. Through this QI initiative, teams identified gaps/barriers in their own practices, and developed and implemented action plans for improvement. These data and actionable insights support effective and evidence-based integration of biomarker testing in advanced NSCLC to optimize patient outcomes that can help inform improvement strategies for NSCLC care teams in community settings nationwide. [Table: see text]
High Prevalence of Hypercalcitoninemia in a Large Cohort of Adult and Pediatric Patients With PTH Resistance Syndromes
Authors: Cremaschi Arianna , Del Sindaco Giulia , Pagnano Angela , Dolci Alessia , Berkenou Jugurtha , Rothenbuhler Anya , Contarino Andrea , Ferrante Emanuele , Arosio Maura , Giannetta Elisa , Linglart Agnès , Mantovani Giovanna
Published: June 2024

Context

Pseudohypoparathyroidism (PHP) refers to a group of rare hereditary disorders associated with resistance to parathyroid hormone (PTH) and other hormones now termed inactivating PTH/PTHrP disorders (iPPSD). Hypercalcitoninemia has been seldom reported in small series.

Objective

Our aim was to investigate the characteristics of hypercalcitoninemia in pediatric and adult patients with PHP/iPPSD.

Methods

We retrospectively collected data from 2 cohorts from 2 European endocrinology tertiary centers: the pediatric cohort comprised 88 children with available calcitonin (CT) measurements; the adult cohort included 43 individuals with simultaneous CT and PTH measurements.

Results

In the pediatric cohort, 65.9% had hypercalcitoninemia (median CT 15 ng/L); in the adult cohort 53.5% (mean CT 21.6 ng/L). There was no difference between CT in pediatric and adult population; we observed stable CT levels over a median follow-up of 134.5 months in adults. Notably, no correlations were detected between CT and PTH levels. Other etiologies of hypercalcitoninemia were excluded; adult patients underwent regular thyroid ultrasound to screen for medullary thyroid cancer (MTC). We performed 20 calcium stimulation tests in adult patients. While there was a significant difference in basal and peak CT between our patients, healthy subjects, and subjects with MTC, there was no difference with patients with C-cell hyperplasia.

Conclusion

This study underscores the common occurrence of hypercalcitoninemia in both pediatric and adult patients with PHP/iPPSD, in particular with subtypes iPPSD2 and iPPSD3. Furthermore, these patients show hyperresponsiveness to calcium stimulation tests falling between healthy subjects and patients with MTC. These findings contribute to the understanding of CT dynamics in the context of PHP/iPPSD.
Simple prerequisite of presequence for mitochondrial protein import in the unicellular red alga Cyanidioschyzon merolae
Authors: Hirata Riko , Mogi Yuko , Takahashi Kohei , Nozaki Hisayoshi , Higashiyama Tetsuya , Yoshida Yamato
Published: June 2024

Mitochondrial biogenesis relies on hundreds of proteins that are derived from genes encoded in the nucleus. According to the characteristic properties of N-terminal targeting peptides (TPs) and multi-step authentication by the protein translocase called the TOM complex, nascent polypeptides satisfying the requirements are imported into mitochondria. However, it is unknown whether eukaryotic cells with a single mitochondrion per cell have a similar complexity of presequence requirements for mitochondrial protein import compared to other eukaryotes with multiple mitochondria. Based on putative mitochondrial TP sequences in the unicellular red alga Cyanidioschyzon merolae, we designed synthetic TPs and showed that functional TPs must have at least one basic residue and a specific amino acid composition, although their physicochemical properties are not strictly determined. Combined with the simple composition of the TOM complex in C. merolae, our results suggest that a regional positive charge in TPs is verified solely by TOM22 for mitochondrial protein import in C. merolae. The simple authentication mechanism indicates that the monomitochondrial C. merolae does not need to increase the cryptographic complexity of the lock-and-key mechanism for mitochondrial protein import.
Aggregate and Intergenerational Implications of School Closures: A Quantitative Assessment
Authors: Jang Youngsoo , Yum Minchul
Published: June 2024

This paper quantitatively investigates the medium- and long-term macroeconomic and distributional consequences of school closures through intergenerational channels. The model economy is a dynastic overlapping-generations general equilibrium model in which schools, in the form of public education investments, complement parental investments in producing children’s human capital. We find that unexpected school closure shocks have long-lasting adverse effects on macroeconomic aggregates and reduce intergenerational mobility, especially among older children. Higher substitutability between public and private investments induces smaller damages in the aggregate economy and the affected children’s lifetime income while exacerbating negative impacts on intergenerational mobility and inequality. (JEL D31, E24, I26, I28, J22, J62)
Reassessing the Relevance of Financial Shocks in an Estimated Heterogeneous Firm Model
Authors: Guo Xing
Published: June 2024

I study the transmission of financial shocks using an estimated heterogeneous firm model. Following a contractionary financial shock, financially constrained firms cut investment, but unconstrained firms increase investment due to the lower capital price and interest rate. After matching the empirical dynamics of prices and the price elasticity of investment, I find a limited role of the unconstrained firms’ response in dampening the aggregate investment decline. Nonfinancial capital adjustment friction is the key to generating this result. Without the capital adjustment friction, unconstrained firms’ investment becomes unrealistically sensitive to prices, and the model would understate the financial shocks’ aggregate relevance. (JEL D25, E12, E22, G31, G32)
MPC Heterogeneity and the Dynamic Response of Consumption to Monetary Policy
Authors: Ampudia Miguel , Cooper Russell , Le Blanc Julia , Zhu Guozhong
Published: June 2024

This paper studies how household financial choices affect the impact of monetary policy on consumption. Based on micro data from four major euro area countries, we estimate key structural parameters using a simulated method of moments approach to match moments related to asset market participation rates, portfolio shares, and wealth-to-income ratios by education and country. The country-specific distributions of marginal propensities to consume (MPCs) out of income and financial wealth are not degenerate. Due to this MPC heterogeneity, monetary policy, operating through income and asset returns, has a differential impact on individuals within and across countries. (JEL E21, E52, G51)
Adenosine modifications impede SARS-CoV-2 RNA-dependent RNA transcription
Authors: Snyder Laura R. , Kilde Ingrid , Nemudryi Artem , Wiedenheft Blake , Koutmos Markos , Koutmou Kristin S.
Published: June 2024

SARS-CoV-2, the causative virus of the COVID-19 pandemic, follows SARS and MERS as recent zoonotic coronaviruses causing severe respiratory illness and death in humans. The recurrent impact of zoonotic coronaviruses demands a better understanding of their fundamental molecular biochemistry. Nucleoside modifications, which modulate many steps of the RNA life cycle, have been found in SARS-CoV-2 RNA, although whether they confer a pro- or antiviral effect is unknown. Regardless, the viral RNA-dependent RNA polymerase will encounter these modifications as it transcribes through the viral genomic RNA. We investigated the functional consequences of nucleoside modification on the pre-steady state kinetics of SARS-CoV-2 RNA-dependent RNA transcription using an in vitro reconstituted transcription system with modified RNA templates. Our findings show thatN6-methyladenosine and 2′-O-methyladenosine modifications slow the rate of viral transcription at magnitudes specific to each modification, which has the potential to impact SARS-CoV-2 genome maintenance.
Risk factors and nomogram predictive model of severe postoperative complications in elderly patients with intertrochanteric fractures
Authors: Xu Ping , Xu Yanqiu
Published: June 2024

Objective: To analyze risk factors of severe postoperative complications in elderly patients with intertrochanteric fractures (ITF), and to construct a predictive model.
Methods: The medical records of 316 elderly patients with ITF who underwent surgical treatment in Suzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2020 to December 2022 were retrospectively analyzed. Univariate and multivariate logistic regression analyses were performed to identify risk factors of severe postoperative complications. A nomogram prediction model was constructed using the RMS package of R4.1.2 software. Accuracy and stability of the model was assessed using the receiver operating characteristic (ROC) curve, Hosmer-Lemeshow goodness-of-fit test, and decision curve analysis.
Results: Age, American Society of Anesthesiologists (ASA) grading, combined medical diseases, preoperative bedridden condition, frailty, and preoperative albumin levels were all risk factors for severe postoperative complications in ITF patients were noted. These factors were then used to build a risk prediction model that had an area under the ROC curve (AUC) of 0.899 (95% confidence interval (CI): 0.846-0.951). The internal validation results of the Bootstrap method showed that the C-index value of the model was 0.899, and the calibration curve had a good fit with the ideal curve.
Conclusions: Age, ASA grading, combined medical diseases, preoperative bedridden condition, frailty, and preoperative albumin levels were independent risk factors for severe postoperative complications in elderly ITF patients. The constructed prediction model based on the above risk factors has a high predictive value.
doi: https://doi.org/10.12669/pjms.40.7.9242
How to cite this: Xu P, Xu Y. Risk factors and nomogram predictive model of severe postoperative complications in elderly patients with intertrochanteric fractures. Pak J Med Sci. 2024;40(7):1566-1571. doi: https://doi.org/10.12669/pjms.40.7.9242
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.
Influence of E-Wom, Innovation, E-Trust, and Website Attractiveness on Purchase Decision
Authors:   Fakultas Ekonomi dan Bisnis, Universitas Ahmad Dahlan, Yogyakarta, Solikhah EfA Wakhidatus , Garad Askar ,   Faculty of Managerial and Financial Sciences, University of Saba Region, Marib Province,Yemen
Published: June 2024

Abstract. This research explores the impact of product innovation, website attractiveness, electronic word of mouth (e-WOM), and electronic trust (e-trust) on consumer purchasing decisions in the context of online transactions. In this explanatory quantitative study, the sample consists of 142 consumers who made online purchases through company website accounts. Data collection was conducted using questionnaires, and analysis was performed through the Structural Equation Modeling (SEM) approach with the assistance of SPSS software. The research results indicate that all variables, namely product innovation, website attractiveness, e-WOM, and e-trust, significantly and positively influence consumer purchasing decisions. These findings provide in-depth insights into the factors affecting consumer preferences in online purchases, with key roles played by e-WOM, online reputation, online social interaction, website attractiveness, and electronic trust. Practical implications emphasize the need for companies to focus on the development of attractive websites, the management of e-WOM, and the establishment of an online trust to enhance consumer purchasing decisions online. In conclusion, product innovation is also a crucial factor in capturing consumer attention in the competitive online environment. By implementing these findings, companies can design more effective marketing strategies, enhance online attractiveness, build consumer trust, and ultimately improve consumer purchasing decisions. Keywords: E-WoM, e-trust, web attractiveness, inovasi, dan purchase decision
Działalność balearskiego nadawcy publicznego IB3 a język kataloński
Authors: Głuszek-Szafraniec Dagmara
Published: June 2024

Baleary należące do obszaru kultury katalońskiej i języka katalońskiego są istotnym obszarem kształtowania katalońskojęzycznej wspólnoty komunikacyjnej. Na wyspach, podobnie jak w wielu innych wspólnotach autonomicznych, działa nadawca publiczny. Jego siła, popularność i program mają potencjalny wpływ na sytuację językową w regionie. Dlatego też warto przyjrzeć się sposobowi, w jaki funkcjonuje, oraz ofercie, którą prezentuje w swoich kanałach radiowych czy telewizyjnych. Celem artykułu jest przedstawienie statusu mediów publicznych na Balearach, ich roli w promocji języka katalońskiego, popularności oraz problemów, z jakimi muszą się mierzyć. Główną metodą badawczą jest analiza systemowa odnosząca się do rynku medialnego Hiszpanii. Niestabilność zarządzania i finansowania balearskich mediów publicznych nie przyczynia się do ich popularności wśród użytkowników mediów. Słaba pozycja na rynku może stać się przyczyną nierealizowania zadań misyjnych, do których należy również popularyzacja języka katalońskiego wśród mieszkańców Balearów.
Establishing Convergence of Infinite-Server Queues with Batch Arrivals to Shot-Noise Processes
Authors: Daw Andrew , Fralix Brian , Pender Jamol
Published: June 2024

Stronger Connections and Uncovered Nuance for Queues with Batch Arrivals

Many modern queueing systems face the challenge that arrivals occur in batches of customers or jobs. Such simultaneity in the arrival stream may place a particularly acute stress on the service system. Recently, researchers have identified that shot-noise processes, a family of stochastic models for which the dynamics are deterministic between arrival epochs, can be used to approximate batch-arrival queues as justified through batch scaling limits. In “Establishing Convergence of Infinite-Server Queues with Batch Arrivals to Shot-Noise Processes,” Daw, Fralix, and Pender both elevate and generalize these limits, moving from point-wise convergence in distribution for Markovian models to almost sure convergence on a process level (uniformly on compact sets) for general arrival and service processes, allowing for possible nonstationarity and dependence between arrivals. Additionally, the authors establish these batch-scaling limits for both the queue-length and workload processes, and this leads to an unexpected insight. By comparison with the Markovian case, in which the queue-length and workload limits are proportionally identical, for general service distributions, the batch-scaled queue-length and workload processes can differ significantly, revealing that the workload can persist even as the queue length dwindles.
The Gender Disclosure Gap: Salary History Bans Unravel When Men Volunteer Their Income
Authors: Cowgill Bo , Agan Amanda , Gee Laura K.
Published: June 2024

This study investigates whether the success of salary history bans could be limited by job-seekers volunteering their salaries unprompted. We survey American workers in 2019 and 2021 about their recent job searches, distinguishing when candidates were asked about salary history from when they were not. Historically well-paid workers may have an incentive to disclose, and employers who are aware of this could infer that nondisclosing workers are concealing low salaries. Through this mechanism, all workers could face pressure to avoid the stigma of silence. Our data shows a large percentage of workers (28%) volunteer salary history, even when a ban prevents employers from asking. An additional 47% will disclose if enough other job candidates disclose. Men are more likely than women to disclose their salaries unprompted, especially if they believe other candidates are disclosing. Over our 1.5-year sample covering jurisdictions with (and without) bans, unprompted volunteering of salary histories increased by about 6–8 percentage points.

Funding: This work was supported by W.E. Upjohn Institute for Employment Research; Ewing Marion Kauffman Foundation (Emerging Scholars Program).

Supplemental Material: The online appendix is available at https://doi.org/10.1287/orsc.2023.17384 .
Percepção da variação sociolinguística: a avaliação social da alternância entre o ditongo nasal átono final e vogal oral na variedade carioca
Authors: Abreu Gomes Christina , Gaspar de Assis Silva Giselle
Published: June 2024

Uma das questões do estudo da variação e da mudança linguística diz respeito à avaliação social das variantes. Este artigo discorre sobre a dinâmica da variação linguística na comunidade de fala do Rio de Janeiro, focalizando a avaliação das variantes da alternância entre ditongo nasal átono final e vogal oral. A avaliação social das variantes foi acessada por meio de experimento que utiliza a técnica matched-guise. O experimento envolveu a apresentação de estímulos orais aos participantes, isto é, sentenças veículo contendo item lexical com as variantes da variável em análise. A tarefa consistiu em associar o estímulo ouvido a uma das duas fotos apresentadas, caracterizando o falante da sentença em função de status socioeconômico. Nenhum participante ouviu o mesmo item lexical com as duas variantes. Além disso, o sexo do falante foi uma condição between-subjects. Os objetivos do experimento foram verificar em que medida há a tendência a se associar cada variante a um determinado perfil social, para acessar o valor social das variantes, e se condicionamentos estruturais afetam a percepção. O experimento foi aplicado a vinte e três participantes e as respostas foram submetidas a tratamento estatístico, usando modelos mistos. Os resultados mostraram que a variante vogal oral não indexa status socioeconômico baixo na variedade carioca, o que confirma o caráter de marcador linguístico da variável em questão. Foi também observado efeito de condicionamentos linguísticos no limite da significância na percepção das variantes.
Bringing the team together
Authors: Brown Clementine Rees
Published: June 2024

Clementine Rees Brown reviews this year's Invisalign Live event.
An immersive experience
Authors: Brown Clementine Rees
Published: June 2024

Clementine Rees Brown details Solventum's dive into the art world and latest launch.
A need for discussion
Authors: Garlo Nina
Published: June 2024

Nina Garlo speaks with experts about the links between gum disease and stroke risk in young adults.
Making an ‘IMPACT’: putting policies and research into practice
Authors: Glasby Jon
Published: June 2024

Jon Glasby discusses IMPACT, a national evidence-informed centre that helps care providers to improve their way of working.
Impact of Clinical Learning Environment and Incivility on Professional Self-Concept in Dental Hygiene Students
Authors: Lee Mi-Ra
Published: June 2024

Objective: This study aimed to investigate how the clinical learning environment and experiences of incivility during clinical practice influence the professional self-concept of dental hygiene students. Methods: A survey was administered to 180 dental hygiene students in the Chungcheong region, and the data collected were analyzed. Results: Higher levels of satisfaction with the major and clinical practice were associated with a more positive clinical learning environment and reduced incidence of incivility. Students with higher academic grades, greater satisfaction with their major, and exposure to more experienced clinical instructors demonstrated higher levels of professional self-concept. There exists a negative correlation between the clinical learning environment and incivility, and a positive correlation between the clinical learning environment and professional self-concept. Clinical learning environment and major satisfaction emerged as factors influencing professional self-concept, explaining 37.5% of the variance. Conclusions: A positive perception of the clinical learning environment affects professional self-concept. Therefore, the development of health education programs aimed at enhancing the clinical education environment for dental hygiene students, alongside specific strategies to bolster major satisfaction, is essential for fostering a robust positive professional self-concept.
Evaluation for Advanced Detection Method of Tooth, Head, and Neck Structures using LowFrequency Components
Authors: Kim Kyuseok , Jung Eun-Ha
Published: June 2024

Objective: In dental radiography, information distorted by scatter radiation and superimposition is reflected. There is a disadvantage that the discrimination is low, especially in the case of lowcontrast materials. To overcome this problem, a low-frequency component based contrast enhancement algorithm for radiographic images was established and implemented effectively. We assessed a sophisticated technique for identifying tooth, head, and neck structures using low-frequency components for dental professions. Methods: Based on a low-frequency component calculation using the Fourier transform and contrast enhancement model, we performed contrast enhancement using numerical phantom and intra-oral radiographic images. Results: The proposed method confirmed that the discrimination of internal materials with low contrast improved with simulation. The contrast-to-noise ratio of the proposed method was approximately 3.6 and 1.6 times higher than that of original and CLAHE imaging in intra-oral radiography, respectively. Conclusion: This study showed that the proposed approach provides a high ability to distinguish the entire dynamic range without controlling the window, and also significantly maintains the sharpness of the internal material. Increased expression in the area of tooth overlap, increased contrast of dentin, and improved detection of early caries were confirmed.
Mental Health According to DISC Behavioral Types in Dental Hygiene Students
Authors: Han Se-Young
Published: June 2024

Objective: By identifying the relationship between mental health, DISC behavioral types, and stress in clinical practice among dental hygiene students, this study aimed to provide a reference base for developing a variety of tailored educational programs for mental health promotion. Methods: We conducted a survey using self-administered questionnaires distributed to dental hygiene students enrolled in three colleges located in Gyeongsangbuk-do Province between February 19 and 29, 2024. Results: The subjects’mean mental health score was 66.27±36.04. A analysis of the correlation between mental health and each variable established that mental health had a significant negative correlation with behavior types, and a significant positive correlation with clinical practice stress. Factors affecting mental health were selected as significant variables, these variables explained 23% of the variance. Conclusions: To strengthen the mental health of dental hygiene students in today’s rapidly changing environment, a variety of tailored education programs need to be developed and applied by identifying emotional factors influencing students’mental health.
Guidelines for Promoting Household Financial Wellbeing in Bang Kruai District, Nonthaburi Province
Authors:   Doctoral Program in Human and Community Resource Development, Faculty of Education and Development Sciences, Kasetsart University, Nakhon Pathom, Thailand, Chearnkaitpradab Jirawut , Yamtim Varaporn ,   Department of Human and Community Resource Development, Faculty of Education and Development Sciences, Kasetsart University, Nakhon Pathom, Thailand, Jaiaree Apichart ,   Department of Human and Community Resource Development, Faculty of Education and Development Sciences, Kasetsart University, Nakhon Pathom, Thailand
Published: June 2024

This article uses quantitative methods to achieve two objectives: assessing the needs of and creating suitable and appropriate guidelines for promoting financial wellbeing of households in Bang Kruai district, Nonthaburi province, Thailand. The sample group provided with questionnaires consisted of 400 representatives of households, obtained by multi-stage sampling. The statistics used for data analysis were descriptive statistics such as frequency, percentage, Mean, standard deviation and the priority need index (PNI modified). We found that households have needs for financial decision-making, including spending and buying items as needed, earning extra income, increasing investment financial capacity, planning spending, and earning income and expense control. Regarding financial sense, confidence that there is money available in case of an emergency is important, as well as an absence of concern over income and expenses, and satisfaction with household savings. Our guidelines for promoting household financial wellbeing included financial planning for reserves, fund management and investments to generate returns, spending according to the philosophy of sufficiency economy, and organizing activities and saving projects.