bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring Minimal Residual Disease in Patients with Multiple Myeloma by Targeted Tracking Serum M-Protein Using Mass Spectrometry (EasyM)
Authors: Fan Huishou , Wang Bing , Shi Lihui , Pan Ni , Yan Wenqiang , Xu Jingyu , Gong Lixin , Li Lingna , Liu Yuntong , Du Chenxing , Cui Jian , Zhu Guoqing , Deng Shuhui , Sui Weiwei , Xu Yan , Yi Shuhua , Hao Mu , Zou Dehui , Chen Xiequn , Qiu Lugui , An Gang
Published: January 2024

Purpose:

We investigated both the clinical utilities and the prognostic impacts of the clonotypic peptide mass spectrometry (MS)-EasyM, a blood-based minimal residual disease (MRD) monitoring protocol in multiple myeloma.

Experimental Design:

A total of 447 sequential serum samples from 56 patients with multiple myeloma were analyzed using EasyM. Patient-specific M-protein peptides were sequenced from diagnostic samples; sequential samples were quantified by EasyM to monitor the M-protein. The performance of EasyM was compared with serum immunofixation electrophoresis (IFE), bone marrow multiparameter flow cytometry (MFC), and next-generation flow cytometry (NGF) detection. The optimal balance of EasyM sensitivity/specificity versus NGF (10−5 sensitivity) was determined and the prognostic impact of MS-MRD status was investigated.

Results:

Of the 447 serum samples detected and measured by EasyM, 397, 126, and 92 had time-matching results for comparison with serum IFE, MFC-MRD, and NGF-MRD, respectively. Using a dotp >0.9 as the MS-MRD positive, sensitivity was 99.6% versus IFE and 100.0% versus MFC and NGF. Using an MS negative cutoff informed by ROC analysis (<1.86% of that at diagnosis), EasyM sensitivity remained high versus IFE (88.3%), MFC (85.1%), and NGF (93.2%), whereas specificity increased to 90.4%, 55.8%, and 93.2%, respectively. In the multivariate analysis, older diagnostic age was an independent predictor for progression-free survival [PFS; high risk (HR), 3.15; 1.26–7.86], the best MS-MRD status (MS-MRD negative) was independent predictor for both PFS (HR, 0.25; 0.12–0.52) and overall survival (HR, 0.16; 0.06–0.40).

Conclusions:

EasyM is a highly sensitive and minimal invasive method of MRD monitoring in multiple myeloma; MS-MRD had significant predictive ability for survival outcomes.
Transverse Colon Primary Tumor Location as a Biomarker in Metastatic Colorectal Cancer: A Pooled Analysis of CCTG/AGITG CO.17 and CO.20 Randomized Clinical Trials
Authors: Solar Vasconcelos Joao Paulo , Chen Nan , Titmuss Emma , Tu Dongsheng , Brule Stephanie Y. , Goodwin Rachel , Jonker Derek J. , Price Timothy , Zalcberg John R. , Moore Malcolm J. , Karapetis Christos S. , Siu Lillian , Shapiro Jeremy , Simes John , Gill Sharlene , O'Callaghan Chris J. , Loree Jonathan M.
Published: January 2024

Purpose:

Sidedness is prognostic and predictive of anti-EGFR efficacy in metastatic colorectal cancer (mCRC). Transverse colon has been historically excluded from several analyses of sidedness and the optimal division between left- and right-sided colorectal cancer is unclear. We investigated transverse colon primary tumor location as a biomarker in mCRC.

Experimental Design:

Pooled analysis of CCTG/AGITG CO.17 and CO.20 trials of cetuximab in chemotherapy-refractory mCRC. Outcomes of patients with RAS/BRAF wild-type (WT) mCRC from CO.17 and KRAS WT mCRC from CO.20 were analyzed according to location.

Results:

A total of 553 patients were analyzed, 32 (5.8%) with cancers from the transverse, 101 (18.3%) from right, and 420 from (75.9%) left colon. Transverse mCRC failed to reach significant benefit from cetuximab versus best supportive care (BSC) for overall survival [OS; median, 5.9 vs. 2.1 months; HR, 0.63; 95% confidence interval (CI), 0.28–1.42; P=0.26] and progression-free survival (PFS; median, 1.8 vs. 1.3 months; HR, 0.57; 95% CI, 0.26–1.28; P=0.16). Analyzing exclusively patients randomized to cetuximab, right-sided and transverse had comparable outcomes for OS (median, 5.6 vs. 5.9 months; HR, 0.82; 95% CI, 0.50–1.34; P=0.43) and PFS (median, 1.9 vs. 1.8 months; HR, 0.78; 95% CI, 0.49–1.26; P=0.31). Patients with left-sided mCRC had superior outcomes with cetuximab compared with transverse for OS (median, 9.7 vs. 5.9 months; HR, 0.42; 95% CI, 0.27–0.67; P=0.0002) and PFS (median, 3.8 vs. 1.8 months; HR, 0,49; 95% CI, 0.31–0.76; P=0.001). Location was not prognostic in patients treated with BSC alone.

Conclusions:

Transverse mCRC has comparable prognostic and predictive features with right-sided mCRC.
Supplementary Figure legend from SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma
Authors: Akashi Hidehiko , Yachida Nozomi , Ueda Haruka , Yamaguchi Manako , Yamawaki Kaoru , Tamura Ryo , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Nagase Yoshikazu , Ueda Yutaka , Ueda Masashi , Abiko Kaoru , Kagabu Masahiro , Baba Tsukasa , Nakaoka Hirofumi , Enomoto Takayuki , Murai Junko , Yoshihara Kosuke
Published: January 2024

Supplementary Figure legend
Supplementary Figure 2 from SLFN11 is a BRCA Independent Biomarker for the Response to Platinum-Based Chemotherapy in High-Grade Serous Ovarian Cancer and Clear Cell Ovarian Carcinoma
Authors: Akashi Hidehiko , Yachida Nozomi , Ueda Haruka , Yamaguchi Manako , Yamawaki Kaoru , Tamura Ryo , Suda Kazuaki , Ishiguro Tatsuya , Adachi Sosuke , Nagase Yoshikazu , Ueda Yutaka , Ueda Masashi , Abiko Kaoru , Kagabu Masahiro , Baba Tsukasa , Nakaoka Hirofumi , Enomoto Takayuki , Murai Junko , Yoshihara Kosuke
Published: January 2024

Supplementary Figure 2
Figure S2 from Brentuximab Vedotin–Driven Microtubule Disruption Results in Endoplasmic Reticulum Stress Leading to Immunogenic Cell Death and Antitumor Immunity
Authors: Heiser Ryan A. , Cao Anthony T. , Zeng Weiping , Ulrich Michelle , Younan Patrick , Anderson Martha E. , Trueblood Esther S. , Jonas Mechthild , Thurman Robert , Law Che-Leung , Gardai Shyra J.
Published: January 2024

Supplementary Figure S2. ICD hallmarks observed from tumor cell lines treated with brentuximab vedotin or MMAE
Supplementary Table S5 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

The complete list of identified phosphopeptides after pY enrichment in crizotinib vs DMSO treated CUTO28 cells with fold changes and p-value calculation.
Supplementary Figures S1-9 from MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling
Authors: Chen Nan , Tyler Logan C. , Le Anh T. , Welsh Eric A. , Fang Bin , Elliott Andrew , Davies Kurtis D. , Danhorn Thomas , Riely Gregory J. , Ladanyi Marc , Haura Eric B. , Doebele Robert C.
Published: January 2024

Supplementary Figure S1. MIG6 protein reduction correlates with the responsiveness to ALK/ROS1 inhibitors. Supplementary Figure S2. MIG6 expression is decreased by ALK/ROS1 inhibition via the MAPK pathway. Supplementary Figure S3. Gefitinib restores sensitivity to ALK/ROS1 inhibition with MIG6 knockdown. Supplementary Figure S4. MIG6 siRNA knockdown rescues of SHC1-MAPK signaling under crizotinib treatments. Supplementary Figure S5. MIG6 mediates adaptive resistance to KRASG12C inhibition. Supplementary Figure S6. EGFR or ERBB2 amplification was not found in CUTO37-ER cells. Supplementary Figure S7. MIG6 protein is reduced in HCC78-TR and PR2 cells compared to their parental counterparts. Supplementary Figure S8. ERRFI1 alterations in pan-cancer. Supplementary Figure S9. Model depicting MIG6 role in regulating EGFR-mediated adaptive and acquired resistance to ALK/ROS1 inhibition.
Figure S4 from A Novel Irreversible TEAD Inhibitor, SWTX-143, Blocks Hippo Pathway Transcriptional Output and Causes Tumor Regression in Preclinical Mesothelioma Models
Authors: Hillen Hanne , Candi Aurélie , Vanderhoydonck Bart , Kowalczyk Weronika , Sansores-Garcia Leticia , Kesikiadou Elena C. , Van Huffel Leen , Spiessens Lore , Nijs Marnik , Soons Erik , Haeck Wanda , Klaassen Hugo , Smets Wim , Spieser Stéphane A. , Marchand Arnaud , Chaltin Patrick , Ciesielski Fabrice , Debaene Francois , Chen Lei , Kamal Adeela , Gwaltney Stephen L. , Versele Matthias , Halder Georg A.
Published: January 2024

Figure S4 shows A) Immunofluorescence stainings of lung sections from mice with mesothelioma after 2 weeks after Adeno-Cre injection, stained for Vimentin (green) and Mesothelin (red). B) Picture of an H&E staining of a lung section from a mouse with mesothelioma that was treated with SWTX-143 for one week.
Supplementary Table.3 from The Tautomerase Activity of Tumor Exosomal MIF Promotes Pancreatic Cancer Progression by Modulating MDSC Differentiation
Authors: Jia Xuebing , Xi Jianbei , Tian Binle , Zhang Yuanyuan , Wang Zhilong , Wang Fan , Li Zheng , Long Jiang , Wang JianFei , Fan Guo-Huang , Li Qi
Published: January 2024

Chemical potency, physiochemical properties, and mouse pharmacokinetic data of IPG1576.
Supplementary Figure 4 from T cell–Dependent Bispecific Therapy Enhances Innate Immune Activation and Antibody-Mediated Killing
Authors: Besla Rickvinder , Penuel Elicia , Del Rosario Geoff , Cosino Ely , Myrta Szymon , Dillon Mike , Lazar Greg A. , Nickles Dorothee , Spiess Christoph , Yu Shang-Fan , Polson Andrew G.
Published: January 2024

Cytokines produced during TDB-mediated killing impact the NK-cell transcriptome and their function.
Figure S4 from Notch Signaling Regulates Immunosuppressive Tumor-Associated Macrophage Function in Pancreatic Cancer
Authors: Yan Wei , Menjivar Rosa E. , Bonilla Monica E. , Steele Nina G. , Kemp Samantha B. , Du Wenting , Donahue Katelyn L. , Brown Kristee L. , Carpenter Eileen S. , Avritt Faith R. , Irizarry-Negron Valerie M. , Yang Sion , Burns William R. , Zhang Yaqing , Pasca di Magliano Marina , Bednar Filip
Published: January 2024

Single cell analysis of Notch signaling activation in TAMs.
Supplementary Table S1 from Combination of Anti–PD-1 and Electroacupuncture Induces a Potent Antitumor Immune Response in Microsatellite-Stable Colorectal Cancer
Authors: Wang Yuan , Liu Fengyi , Du Xiaoxue , Shi Jiaqi , Yu Rui , Li Shuang , Na Ruisi , Zhao Ying , Zhou Meng , Guo Ying , Cheng Liang , Wang Guangyu , Zheng Tongsen
Published: January 2024

PCR primers
Supplementary Figure S6 from Combination of Anti–PD-1 and Electroacupuncture Induces a Potent Antitumor Immune Response in Microsatellite-Stable Colorectal Cancer
Authors: Wang Yuan , Liu Fengyi , Du Xiaoxue , Shi Jiaqi , Yu Rui , Li Shuang , Na Ruisi , Zhao Ying , Zhou Meng , Guo Ying , Cheng Liang , Wang Guangyu , Zheng Tongsen
Published: January 2024

Supplementary Figure S6 and legend
Supplementary Figure S2 from Combination of Anti–PD-1 and Electroacupuncture Induces a Potent Antitumor Immune Response in Microsatellite-Stable Colorectal Cancer
Authors: Wang Yuan , Liu Fengyi , Du Xiaoxue , Shi Jiaqi , Yu Rui , Li Shuang , Na Ruisi , Zhao Ying , Zhou Meng , Guo Ying , Cheng Liang , Wang Guangyu , Zheng Tongsen
Published: January 2024

Supplementary Figure S2 and legend
Supplementary Figure S3 from Combined Inhibition of EZH2 and FGFR is Synergistic in BAP1-deficient Malignant Mesothelioma
Authors: Badhai Jitendra , Landman Nick , Pandey Gaurav Kumar , Song Ji-Ying , Hulsman Danielle , Krijgsman Oscar , Chandrasekaran Gayathri , Berns Anton , van Lohuizen Maarten
Published: January 2024

Supplementary Figure S3 shows stable body weight of mice treated with the combination.
FIGURE 5 from Combined Inhibition of EZH2 and FGFR is Synergistic in BAP1-deficient Malignant Mesothelioma
Authors: Badhai Jitendra , Landman Nick , Pandey Gaurav Kumar , Song Ji-Ying , Hulsman Danielle , Krijgsman Oscar , Chandrasekaran Gayathri , Berns Anton , van Lohuizen Maarten
Published: January 2024

EZH2 and FGFR combination prolong survival of autochthonous BNC mouse models. A, Schematic representation of the experimental workflow of the autochthonous Bap1-deficient mesothelioma mouse model. B, Kaplan–Meier curve comparing the survival of vehicle-treated, and AZD4547/GSK126-treated mice (n = 11 mice per treatment group). AZD4547 was administered via oral gavage once daily at 5 mg/kg. GSK126 was administered once daily via intraperitoneal injection at 40 mg/kg. Dashed lines indicate start and end of treatment. P value was determined by log-rank (Mantel–Cox) test; **, P < 0.01. C, Thoracic tumor burden of the mice in the cohorts was analyzed and scored by an experienced animal pathologist. P value was determined by two-tailed unpaired Student t test; ****, P < 0.0001. D, Microphotographs of H&E staining showing tumor lesions in myocardium of heart (top) and in thoracic muscle wall (bottom) from treated and vehicle mice. Major parts of the tumor area are highlighted with elliptical boxes. Scale bars: 500 µm. Representative images are shown. E, Kaplan–Meier curve comparing the survival of vehicle-treated, and AZD4547/tazemetostat-treated mice (n = 11 mice per treatment group). AZD4547 was administered via oral gavage once daily at 5 mg/kg. Tazemetostat was administered twice daily via oral gavage at 250 mg/kg. Dashed lines indicate start and end of treatment. P value was determined by log-rank (Mantel–Cox) test; **, P < 0.01. F, Thoracic wall tumor burden of the mice in the cohorts was analyzed and scored by an experienced animal pathologist. P value was determined by two-tailed unpaired Student t test; *, P < 0.05.
FIGURE 1 from Combined Inhibition of EZH2 and FGFR is Synergistic in BAP1-deficient Malignant Mesothelioma
Authors: Badhai Jitendra , Landman Nick , Pandey Gaurav Kumar , Song Ji-Ying , Hulsman Danielle , Krijgsman Oscar , Chandrasekaran Gayathri , Berns Anton , van Lohuizen Maarten
Published: January 2024

Combined FGFR and EZH2 inhibition reveals strong synergy in BAP1-deficient mesothelioma. A, 3D synergy plots visualizing the synergy score for the different concentrations and combinations of FGFR and EZH2 inhibitors in Bap1-proficient (NC) and Bap1-deficient (BNC) mouse mesothelioma cells. Shown are the results of three independent replicates. B, 3D synergy plots visualizing the synergy score for the different concentrations and combinations of the inhibitors in BAP1-proficient (NCI-H2810) and BAP1-deficient (NCI-H2731) human mesothelioma cell lines. Shown are the results of three independent replicates. C, Similar to the data shown in A, the clinically available inhibitor tazemetostat was used as an EZH2 inhibitor instead of GSK126. D, Similar to the data shown in B, the clinically available inhibitor tazemetostat was used as an EZH2 inhibitor instead of GSK126. E, Long-term clonogenicity assays of mouse mesothelioma cell lines treated with DMSO, GSK126 (7.5 µmol/L), AZD4547 (0.75 µmol/L), or the combination. F, Long-term clonogenicity assays of human mesothelioma cell lines treated with DMSO, GSK126 (7.5 µmol/L), AZD4547 (0.75 µmol/L), or the combination. Representative images are shown from three independent experiments. Quantification data are mean ± SEM, n = 3 independent experiments. Representative images are shown from three independent experiments. Quantification data are mean ± SEM, n = 3 independent experiments. G, Similar to the data shown in E, the clinically available inhibitor tazemetostat (10 µmol/L) was used as an EZH2 inhibitor instead of GSK126. H, Similar to the data shown in F, the clinically available inhibitor tazemetostat (10 µmol/L) was used as an EZH2 inhibitor instead of GSK126; images of control wells are duplicated for presentation purposes, P values were determined by using two-tailed unpaired Student t test; ∗, P < 0.05; ∗∗, P < 0.01, ∗∗∗, P < 0.001; and ∗∗∗∗, P < 0.0001.
Primary Peritoneal Carcinosarcoma in a Breast Cancer Patient Harboring a Germline BRCA2 Pathogenic Variant: Case Report
Authors: Mendes Gomes Luciana Beatriz , Lazari Sandoval Renata , Bragança Xavier Camila , Strava Correa Tatiana , Koga Matuda Raquel Midori , Silva de Souza Zenaide , Cernaglia Aureliano de Lima Luiz Guilherme , Petaccia de Macedo Mariana , Marino Carvalho Filomena , Assad Suzuki Daniele
Published: January 2024

Malignant mixed müllerian tumor (MMMT) is a rare neoplasm, consisting of carcinomatous (epithelial) and sarcomatous (mesenchymal) components that most commonly arise in the endometrium and more infrequently in the ovaries, fallopian tube, cervix, and vagina. Primary peritoneal carcinosarcoma (PPCS) is an extremely rare extragenital presentation of MMMT. Although the occurrence of breast cancer and epithelial ovarian carcinoma in association with BRCA pathogenic variants is firmly established, the etiologic role of these genes in the development of other tumor types is less well known. Here, we present a rare case of PPCS in a 42-year-old Brazilian woman with a BRCA2 pathogenic variant, c.2808_2811del (NM_000059.3). The patient developed metastatic breast cancer at the age of 37 and underwent a risk-reducing bilateral salpingo-oophorectomy 2 years later. She was then diagnosed with PPCS 3 years after the risk-reducing surgery. She underwent treatment with surgery, chemotherapy, and targeted therapy but passed away almost 5 years after the second primary tumor diagnosis. To our knowledge, this is the first case of peritoneal carcinosarcoma described in a BRCA2 pathogenic variant carrier, and its report leads to a better understanding of the disease’s molecular features and possible therapeutic approaches.
Comparison of Ultrasound-Guided Umbilical Venous Catheter Insertion with Blind Method: A Randomized Controlled Trial
Authors: Mishra Purbasha , Mohanty Pankaj Kumar , Som Tapas Kumar , Sahoo Tanushree , Devi Usha , Bag Nerbadyswari Deep
Published: January 2024

Introduction: Ultrasonography (USG) can be used in neonates to manipulate and place the umbilical catheter in the correct position. Although chest radiograph (CXR) is the gold standard, a noninvasive method like USG without radiation exposure may be an alternative bedside armamentarium to the clinician. The purpose of the study was to evaluate whether USG-guided umbilical venous catheter (UVC) insertion is superior to the conventional method for the successful insertion of UVC. Method: The neonates born between 25 and 42 weeks of gestation requiring parenteral fluids and admission to neonatal intensive care unit (NICU) between September 2020 and November 2022 were randomized in two weight-based strata: ≤1,200 and >1,200 g. USG-guided UVC insertion was done in the intervention group and blind UVC insertion was done in the control group. Results: Out of 112 enrolled neonates, 58 were in the USG-guided group and 54 in the blind group. There was no significant difference in the failure rate between the intervention and control groups (20% versus 29% [RR: 0.69, 95% CI: 0.36–1.33]). The sensitivity and specificity of USG in locating tip position were 97 and 46.8%, respectively. The mean procedure time in USG and blind groups was 8.9 and 8.3 min, respectively (p value 0.56). Conclusion: USG does not reduce the failure rates during the insertion of umbilical catheters. However, being a safe, noninvasive procedure, it can be considered a rescue modality to CXR in NICUs equipped with portable USG for guiding UVC insertion.
Novel Digenic Variants in COL4A4 and COL4A5 Causing X-Linked Alport Syndrome: A Case Report
Authors: Uedono Hideki , Mori Katsuhito , Nakatani Shinya , Watanabe Kohei , Nakaya Rino , Morioka Fumiyuki , Sone Kazuma , Ono Chie , Hotta Junko , Tsuda Akihiro , Morisada Naoya , Seto Toshiyuki , Nozu Kandai , Emoto Masanori
Published: January 2024

Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear. Here, we present a case of digenic AS with novel digenic missense variants in COL4A4 (c.827G>C, p.Gly276Ala) and COL4A5 (c.4369G>C, p.Gly1457Arg). Case Presentation: The patient was a 29-year-old Japanese man suffering from persistent microscopic hematuria and proteinuria without kidney function impairment. Kidney biopsy showed focal interstitial foam cell infiltration, global and segmental glomerulosclerosis. Immunofluorescence staining for collagen IV α5 was almost negative in the GBM and Bowman’s capsule. Electron microscopy revealed irregular thickening with lamellation and segmental thinning of the GBM. Clinical and pathological findings were consistent with AS. Comprehensive next-generation sequencing revealed a heterozygous missense variant in COL4A4 (c.827G>C, p.Gly276Ala) in exon 1 and a hemizygous missense variant in COL4A5 (c.4369G>C, p.Gly1457Arg) in exon 49 on the patient’s paternal and maternal alleles, respectively. The same digenic variants were detected in his sister, and she also showed a similar phenotype. After treatment with angiotensin-converting enzyme inhibitors, proteinuria decreased from 2.3 to 1.1 g/g creatinine, but occult blood persisted. During follow-up, kidney function has been preserved. Conclusion: The novel genotype of our case provides more information on the genotype-phenotype correlation of digenic XLAS, although long-term follow-up is required. The findings in the present case also indicate the importance of genetic tests for family members of a patient diagnosed with digenic AS.
Stabilizing Hypoxia-Inducible Factor to Manage Anemia in Chronic Kidney Disease: From Basic Theory to Clinical Study
Authors: Wang Yudian , Yu Xiaoyong
Published: January 2024

Background: Anemia is one of the common complications of chronic kidney disease (CKD), and its prevalence has been arising globally. The key cause of anemia in CKD patients is the diseased kidney’s reduced ability to synthesize endogenous erythropoietin (EPO), yet this is not the sole reason. Inflammatory elements, functional iron deficiency, and uremic toxins together participate in the development of anemia. According to research data, anemia is an independent risk factor for cardiovascular events, all-cause mortality, and worsening renal function and affects the clinical prognosis and quality of life of CKD patients. Regular treatments for anemia in CKD patients include the use of erythropoiesis-stimulating agents (ESAs), iron supplements, and blood transfusions. Summary: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are novel and small-molecule pharmacological compounds that target the hypoxia-inducible factor (HIF) pathway and are another option for improving anemia in CKD patients. HIF-PHIs simulate hypoxia, stabilize HIF protein, stimulate EPO synthesis, reduce hepcidin level, boost iron utilization, induce the creation of red blood cells, and alleviate anemia. The results of several HIF-PHI phase III trials indicated that HIF-PHIs are similarly effective as ESA at raising hemoglobin concentration. Key Messages: This article summarizes the structure of HIF and the mechanism of stabilizing HIF to improve anemia, discusses the efficacy of HIF-PHIs in CKD patients with or without dialysis, as well as emphasizes the potential safety concerns with HIF-PHIs.
Spacetime Is Doomed: Time Is an Artifact
Authors: Hoffman Donald D.
Published: January 2024

It is well known that spacetime has no operational meaning beyond the Planck scale. In consequence, many high-energy theoretical physicists are seeking, and finding, new structures entirely beyond spacetime. In light of these advances, we propose that time is not fundamental. The arrow of time is an artifact of projection of a stationary dynamics, entirely beyond spacetime and quantum theory, whose entropy does not increase.
Baltic Abstracts in *-ī-bā
Authors: Ostrowski Norbert
Published: January 2024

Baltic abstracts in -ība (e.g. Lith. dial. gyvýba ‘life’ / Latv. dzīvība ‘life’) are built on the basis of the old abstract formations in *-ī < IDE *-ih2, acc.sg. *-ijan. From the acc.sg. *-ijan, a new nom.sg. was formed in *-ijā, which supplanted the inherited nom.sg. *-ī. This, in turn, led to the merger of three different categories of derivatives: adjectival abstracts in *-ī (=> *-ijā), adjectival abstracts in *-ijā, and deverbal abstracts in *-ijā. In the current Lithuanian language, all these types are continued by adjectival abstracts in -ė and deverbal abstracts in -ė.
Northern Kresy Polish – a Summary of Research
Authors: Golachowska Ewa , Ostrówka Małgorzata , Sawaniewska-Mochowa Zofia , Zielińska Anna
Published: January 2024

This article presents a concise overview of research on the Northern Kresy variety of the Polish language (polszczyzna północnokresowa). There is extensive literature on the subject, but there is still no comprehensive bibliography which would accurately document the rich legacy of several generations of researchers working in this field of study.
Northern Kresy Polish is a variety of the Polish language which formed in the historical Slavic-Baltic borderland, mainly as a result of the processes of Polonisation of the local population. Contacts between various ethnolinguistic communities resulted in significant social and territorial diversity of Northern Kresy Polish in the seventeenth and eighteenth centuries. The differences between its variants consist mainly in the frequency of features and the scale of influence of local languages and dialects on the grammatical system and vocabulary of Polish. Nevertheless, it is possible to identify a set of constitutive features of Northern Kresy Polish which function throughout its entire geographical area. Currently, Northern Kresy Polish is defined as the language of the Polish minority in Belarus, Lithuania and Latvia. It is apparent that the Polish language in all of these countries is in decline.
Fully Automated Agatston Score Calculation From Electrocardiography-Gated Cardiac Computed Tomography Using Deep Learning and Multi-Organ Segmentation: A Validation Study
Authors: Gautam Ashish , Raghav Prashant , Subramaniam Vijay , Kumar Sunil , Kumar Sudeep , Jain Dharmendra , Verma Ashish , Singh Parminder , Singhal Manphoul , Gupta Vikash , Rathore Samir , Iyengar Srikanth , Rathore Sudhir
Published: January 2024

To evaluate deep learning-based calcium segmentation and quantification on ECG-gated cardiac CT scans compared with manual evaluation. Automated calcium quantification was performed using a neural network based on mask regions with convolutional neural networks (R-CNNs) for multi-organ segmentation. Manual evaluation of calcium was carried out using proprietary software. This is a retrospective study of archived data. This study used 40 patients to train the segmentation model and 110 patients were used for the validation of the algorithm. The Pearson correlation coefficient between the reference actual and the computed predictive scores shows high level of correlation (0.84; P < .001) and high limits of agreement (±1.96 SD; −2000, 2000) in Bland–Altman plot analysis. The proposed method correctly classifies the risk group in 75.2% and classifies the subjects in the same group. In total, 81% of the predictive scores lie in the same categories and only seven patients out of 110 were more than one category off. For the presence/absence of coronary artery calcifications, the deep learning model achieved a sensitivity of 90% and a specificity of 94%. Fully automated model shows good correlation compared with reference standards. Automating process reduces evaluation time and optimizes clinical calcium scoring without additional resources.
From Italy to the Indian subcontinent: Dante and his Divine Comedy in Urdu
Authors: Masood Hafiz Abid
Published: January 2024

Dante Alighieri (1265–1321) is one of the most important Italian writers, well-known for his magnum opus the Divine Comedy. This article investigates the Urduphone world's engagement with Dante from the late 19th century to the post-colonial period. As India was ruled by the British, English writers, specifically Shakespeare and Milton, were the most famous foreign literary figures in colonial India. Dante, even though he had no official patronage, also made his appearance in Urdu print culture and is frequently referred to by Urdu writers and critics. There are three distinct ways in which Dante is engaged with in Urdu. The first dimension concerns essays about Dante's life and work in Urdu periodicals, and this article will present an overview of these. Secondly, several full and partial translations of the Divine Comedy have been produced in Urdu. This dimension is particularly significant because of Dante's treatment of Prophet Mūḥammad in the Divine Comedy, and the article will attempt to highlight the strategies used by translators to deal with those passages. Finally, Dante has frequently been juxtaposed with Mūḥammad Iqbāl because of the similarities between the Divine Comedy and Javed Nama, both said to be modeled after the story of Miʿrāj in Islam. The article argues that this engagement with Dante in Urdu resulted due to the Divine Comedy's inspiration from Muslim sources, as claimed by the Spanish orientalist Miguel Asin Palacios in his book Islam and the Divine Comedy.
The Politics of State-level COVID-19 Responses in India: Evidence from the First Wave in 2020
Authors: Jain Ritika , Chatterjee Tirtha
Published: January 2024

We examine if policy interventions to curb the spread of COVID-19 were driven by political factors. We focus on the period between 1 June and 31 August 2020 when lockdowns and testing were the only responses available with governments and policymakers across the world. These instruments are costly. Stringent lockdowns post challenges to livelihoods while only testing without any lockdown accentuates health risks. This choice between life and livelihood becomes all the more pertinent in a developing country like India. We find that state governments in India that had upcoming elections, faced close margin victory in the last election, were non-incumbents and were aligned with the party at the centre adhered to aggressive testing as a strategy and did not impose strict lockdowns to avert losses in economic activity. Such policy responses indicate an attempt to avert possible losses in future elections. These findings confirm the strong role of political factors in policy decisions.

JEL Codes: P52, P16, P36
Post-consumer high density polyethylene/zirconium phosphate and aluminum hydroxide composites: Assessment of physico-mechanical and flame retardancy properties
Authors: Albitres GAV , Garcia EE , Soares CMF , Freitas DFS , Neto RP Cucinelli , Mendes LC
Published: January 2024

Regarding environmental preservation, the upcycling of plastics from petroleum source is a consistent alternative. This work intended to investigate melting extruded composites of post-consumer HDPE (rHDPE) filled with pristine zirconium phosphate (ZrP), aluminum hydroxide [Al(OH)3] and aluminum hydroxide modifying-zirconium phosphate [ZrPOct/Al(OH)3]. Physico-mechanical and flame retardancy were assessed. FTIR revealed that rHDPE brought some degree of oxidative degradation probably from its cleaning process and/or processing. By nuclear magnetic resonance at time domain, rHDPE showed three relaxation domains. Fillers induced the lowering of rHDPE relaxation time owing to polymer/filler by hydrogen bonds. Diffraction pattern of rHDPE/Al(OH)3 and rHDPE/ZrPOct/Al(OH)3 indicated better fillers’ dispersion. Fillers changed rHDPE crystallinity degree and thermal stability but rheologic properties were invariable. For all composites, elastic modulus increased (up to 17%) indicating stiffening. Yield strength did not change but stress and strain at break decreased. For the composites, SEM/EDS showed better dispersion and distribution of ZrP and ZrPOct/Al(OH)3 particles. It was assumed that ZrP and ZrPOct/Al(OH)3 greatly increased the flame retardancy. The work corroborates the importance of polymers’ upcycling, and it is in consonance with the objectives of 2030 Agenda released by United Nations.
Redefining Mucosal Inflammation with Spatial Genomics
Authors: Caetano A.J. , Sharpe P.T.
Published: January 2024

The human oral mucosa contains one of the most complex cellular systems that are essential for normal physiology and defense against a wide variety of local pathogens. Evolving techniques and experimental systems have helped refine our understanding of this complex cellular network. Current single-cell RNA sequencing methods can resolve subtle differences between cell types and states, thus providing a great tool for studying the molecular and cellular repertoire of the oral mucosa in health and disease. However, it requires the dissociation of tissue samples, which means that the interrelationships between cells are lost. Spatial transcriptomic methods bypass tissue dissociation and retain this spatial information, thereby allowing gene expression to be assessed across thousands of cells within the context of tissue structural organization. Here, we discuss the contribution of spatial technologies in shaping our understanding of this complex system. We consider the impact on identifying disease cellular neighborhoods and how space defines cell state. We also discuss the limitations and future directions of spatial sequencing technologies with recent advances in machine learning. Finally, we offer a perspective on open questions about mucosal homeostasis that these technologies are well placed to address.
Electricity generation and China's GDP growth under dual control policy
Authors: Xia Longji , Liu Yun
Published: January 2024

To achieve the carbon neutralization plan by 2060, China implemented the “Dual Control” ( Neng Hao Shuang Kong in Chinese) policy in 2015 by limiting the energy intensity and consumption, leading to forced slowdown of energy-related production and consumptions, which in turn hampered China's economic growth. The economic impact of energy shortage has been discussed in such studies as Cheng et al., the economic consequences of the new policy remain unanswered. In this article, we select China's provincial GDP and electricity generation data from 2001 to 2021 to perform causality tests and a double log model which delineates the nexus between GDP growth and electricity generation. We find that (a) electricity generation growth Granger causes GDP growth but not vice versa, and (b) a 1% increase in electricity generation growth will lead to 0.17% increase in GDP growth. The significance of the finding is: as coal still primarily fuels electricity generation, dual control will further hinder China's economic development sans significant enhancement of electric system or expansion of renewable energy, our findings thus support an upgrade of current grid network by China Power International Development; an expansion of renewable capacity such as a proposal of 400 GW new energy project; and construction of energy storage devices such as the CGD Group thermal storage System and Yingcheng Compressed Air Energy Storage System.
Plugging the Tax Leak: An Analysis of North Carolina’s Local Sales Tax Redistribution Policy
Authors: Afonso Whitney , Combs Alex , Buerger Christian
Published: January 2024

Amid rising concerns over the urban-rural divide, taxation equity, revenue generation, and local tax leakage, several states are contemplating measures to support jurisdictions perceived as bearing the brunt of evolving economic landscapes. In 2015, North Carolina introduced a system for local sales tax revenue sharing, wherein each county contributed to a pool of local sales tax revenue, subsequently redistributed among 79 of the 100 counties. This policy aimed to address tax leakage by ensuring that half of the base local sales tax remained at the point of sale, with the other half distributed on a per capita basis. In this analysis, we evaluate the policy’s effectiveness in achieving this equilibrium and identify limitations and shortcomings.
Citizen Preferences and Awareness of Tax Revenue Options: Public Opinion on South Carolina’s “Tax Swap”
Authors: Young Sarah , Thornburg Matthew P.
Published: January 2024

Tax complexity makes it challenging for citizens to understand how taxes imposed by state and local governments affect their tax bill. This paper considers citizen awareness and preferences for tax revenue options in the presence of tax features that increase complexity. The researchers mailed a survey questionnaire to a random sample of South Carolina voters measuring their level of knowledge and preferences for school tax funding during the last half of 2021. A sizable majority of respondents report the property tax as their least preferred option to fund school operations when compared to sales tax or commercial property tax, with variation in support by ideology, homeownership, and partisanship. However, respondents are broadly uninformed of current school tax funding mechanisms regardless of college degree attainment, ideology, and other important indicators. Most respondents are not aware of the “tax swap” that replaced residential property tax with a one-cent sales tax to fund South Carolina school operations.
Effects of the Pandemic on Faculty at Public Research Universities
Authors: Umbach Paul D. , Porter Stephen R. , Willis Chris
Published: January 2024

We provide results from the first national survey of research university faculty on the effect of the COVID-19 pandemic on research productivity and tenure and promotion plans. Our analytic sample consists of almost 4,000 tenured and tenure-line faculty from 31 research universities. A large majority of faculty report disruptions to research due to the pandemic, with time spent moving instruction online listed as the most common cause (80%), followed by travel restrictions (80%) and inability to focus attention (66%). Although the extent of research disruption varied across academic disciplines, the reasons for disruptions were remarkably similar across disciplines. Forty-two percent of junior faculty stated they were likely to extend their tenure clocks due to the pandemic.
Cultural Interpretation as a Theological Task in Northeast India
Authors: Ragui Taimaya
Published: January 2024

Recently, there have been attempts to develop contextual (tribal) Bible reading. While giving priority to these efforts, there appears to be neglect for the cultural interpretation of tribal communities in Northeast India. In light of this reality, as an exegete, I would argue that there is a need to learn to interpret culture to relevantly interpret and translate the text in each context/society. As a case in point of cultural interpretation, an attempt will be made to read the presence and emergence of the Tangkhul confessing community as a text analogue and also as a point of reference for reading-interpreting culture.
Carbon dioxide production index (VCO2i) predicts hyperlactatemia during cardiopulmonary bypass in pediatric carDiac surGery (pGDP- VCO2i): Study protocol for a nested case-control trial
Authors: Zhang Yan , Xiong Hui , Wang Bo , Luo Ming , Liu Ting , Qin Zhen , Fan Jin-Ge , Zhou Rong-Hua
Published: January 2024

Background

Hyperlactatemia (HL) during cardiopulmonary bypass (CPB) is relatively frequent in infants and associates with increased morbidity and mortality. Studies on adults have shown that carbon dioxide production index (VCO2i) during CPB is linked to the occurrence of HL, with ‘critical thresholds’ for VCO2i reported to be 60 mL/min/m2. However, considering infants have a higher metabolic rate and lower tolerance to hypoxia, the critical threshold of VCO2i in infants cannot be replied to the existing adults’ standards. The objective of this study is to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in infants.

Methods

VCO2i predicts hyperlactatemia during cardiopulmonary bypass in pediatric cardiac surgery (pGDP-VCO2i) is a nested case-control study. A cohort of consecutive pediatric patients of less than 3 years of age, undergoing congenital cardiac surgeries between May 2021 and December 2023 in West China Hospital will be enrolled. The VCO2i levels of each patient will be recorded every 5 min during CPB. The primary outcome is the rate of HL. The infants will be divided into two groups based on the presence or not of HL. Pre- and intraoperative factors will be tested for independent association with HL. Then, we will make an analysis, and the critical value of VCO2i will be obtained. The postoperative outcome of patients with or without HL will be compared.

Discussion

This will be the first trial to investigate the association of VCO2i during CPB and HL, and explore the critical VCO2i threshold during CPB in pediatrics. The results of this study are expected to lay a foundation for clinical application of goal-directed perfusion (GDP) management strategy, and optimize the perfusion strategy and improve the prognosis of pediatric patients undergoing cardiac surgery.

Trial registration

Chictr.org.cn, ChiCTR2100044296 on 16 March 2021.
Reactivation of previously controlled Vogt–Koyanagi–Harada disease more than 46 years following COVID-19 vaccination: a case study
Authors: Muto Tetsuya , Sakamoto Masaaki , Imaizumi Shinichiro , Kamoi Koju
Published: January 2024

We report a case of Vogt–Koyanagi–Harada (VKH) disease that recurred 46 years after initial treatment. A 59-year-old woman presented with a 2-month history of bilateral vision blurring. She had received her third dose of coronavirus disease 2019 (COVID-19) vaccination 4 months before the onset of blurring. The best-corrected visual acuity (BCVA) was 1.0 in the right eye and 0.15 in the left eye at the initial visit. Iritis and synechia were observed between the lens and iris bilaterally. A sunset glow fundus was found in both eyes with no serous retinal detachments or disc hyperemia. The patient had a history of VKH disease and had been treated with whole-body corticosteroid administration at another hospital when she was 13 years old. The patient was diagnosed with VKH disease recurrence, and oral corticosteroid therapy and corticosteroid eyedrop treatment were initiated. The treatment response was good. At the time of this writing, recurrence had not been observed for 14 months, and the BCVA was 1.0 in both eyes. To our knowledge, this case represents the longest recorded interval of VKH disease recurrence in the literature to date. COVID-19 vaccination might be the cause of long-term well-controlled disease recurrence.
Realistic U.S. Long-Haul Drive Cycle for Vehicle Simulations, Costing, and Emissions Analysis
Authors: Jones Rob , Köllner Moritz , Moreno-Sader Kariana , Kovács Dávid , Delebinski Thaddaeus , Rezaei Reza , Green William H.
Published: January 2024

Although heavy-duty trucks constitute the backbone of freight transportation in the United States, they also contribute significantly to greenhouse gas emissions. Various alternative powertrains to reduce emissions have been assessed, but few specific to U.S. long-haul applications with a consistent basis of assumptions. To enable a more accurate assessment for all stakeholders, a representative drive cycle for long-haul truck operations in the United States is introduced (USLHC8) for modeling and simulation purposes. This was generated from 58,000 mi of real driving data through a unique random microtrip selection algorithm. USLHC8 covers a total driving time of 10 h 47 min, an average vehicle speed of 55.58 mph, and road grade ranging from −6% to +6%. To establish a benchmark for further powertrain comparisons, a vehicle-level simulation of a conventional diesel powertrain was paired with USLHC8. Benchmarks are presented for fuel consumption, well-to-wheel emissions, and total cost to society under different scenarios (present-day, mid-term, and long-term).
Recent advances in control strategies and algorithms for pilot-operated electro-hydraulic proportional directional valves
Authors: Li Yanchao , Li Ruichuan , Yang Junru , Xu Jikang , Yu Xiaodong
Published: January 2024

Pilot-operated electro-hydraulic proportional directional valve is a key hydraulic component to control the motion of large power equipment such as construction machinery and agricultural equipment. The control accuracy and response speed of the valve control element are very important to the performance of the hydraulic system. In this paper, control strategies for dead-zone control and valve control systems are reviewed. In order to eliminate the dead-zone of pilot-operated proportional valve control, the current control schemes for dead-zone detection and dead-zone compensation are summarized, and the control schemes are evaluated. The proportional–integral–derivative-related control, nonlinear control, and robust control of the pilot-operated electro-hydraulic proportional directional valve control system are reviewed, the relationship between the control strategies is analyzed, and the different control algorithms are evaluated. The shortcomings of the research program are analyzed, and the corresponding solutions are proposed. Based on the current research, future research progresses for eliminating the control dead-zone and optimizing control strategies are presented.
Integrating spiritual disposition intervention into behavioral medicine: A case report on systemic lupus erythematosus from India
Authors: Toor Ishanpreet Kaur , Rastogi Kritika , Ajmani Sajal
Published: January 2024

Background: Systemic Lupus Erythematosus (SLE) is a chronic inflammatory systemic autoimmune disease. The disease manifests as the body’s immune cells start attacking healthy connective tissue, which affects the skin, kidneys, blood vessels, brain, and other vital organs. As with any other chronic illness, the disease has psychological implications.

Purpose: Literature suggests patients with SLE experience anxiety, depression, anger, and stress along with physiological symptoms. There is a strong association between the occurrence of stress and the onset of the disease. These psychological symptoms can be ameliorated through spiritual activities such as meditation, mindfulness, journaling, and reading.

Mehtod: This case report is based on the importance of spirituality in the healthcare system. The study focuses on the concept of a whole-person-centered approach to the medical care industry. Spirituality has been proven to have a positive effect on health and illness. Hence, a 10-week intervention with 30 sessions focusing on spiritual dispositions was provided to the patient for this study, along with regular pharmacological treatment. The present case report is of a 56-year-old woman from New Delhi, India, who was diagnosed with SLE 2 years ago.

Results: The results reveal the positive effect of the intervention, as it led to a significant decrease in stress levels and depressive symptoms; it also resulted in improved quality of life, an enhanced coping style, and bolstered health hardiness. There was an increase in the score of a spiritual personality.

Conlcusion: Spiritual Disposition as an intervention was sucessfull in reducing psychological implications of the disease thus leading to overall positve growth in the patient.