bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmaceuticalisation as the tobacco industry’s endgame
Authors: Hendlin Yogi Hale , Han Elieen Le , Ling Pamela M. 
Published: February 2024

ContextDeclining smoking prevalence and denormalisation of tobacco in developed countries reduced transnational tobacco company (TTC) profit during 1990s and 2000s. As these companies faced increasingly restrictive policies and lawsuits, they planned to shift their business to socially acceptable reduced-harm products. We describe the internal motivations and strategies to achieve this goal.MethodsWe analysed previously secret tobacco industry documents available through the Truth Tobacco Documents Library. These documents were triangulated with TTCs’ investor and other professional reports, websites and public statements.FindingsMimicking pharmaceutical business models, tobacco companies sought to refurbish their image and ensure long-term profitability by creating and selling pharmaceutical-like products as smoking declined. These products included snus, heated tobacco products, e-cigarettes, nicotine gums and inhalers. Tobacco companies created separate divisions to develop and roll out these products, and the majority developed medical research programmes to steer these products through regulatory agencies, seeking certification as reduced-harm or pharmaceutical products. These products were regarded as key to the survival of the tobacco industry in an unfriendly political and social climate.ConclusionsPharmaceuticalisation was pursued to perpetuate the profitability of tobacco and nicotine for tobacco companies, not as a sincere search to mitigate the harms of smoking in society. Promotion of new pharmaceuticalised products has split the tobacco control community, with some public health professionals and institutions advocating for the use of ‘clean’ reduced-harm nicotine and tobacco products, essentially carrying out tobacco industry objectives.
Infant death from accidental suffocation and strangulation in bed in England and Wales: rare or unrecognised events?
Authors: Garstang Joanna Jane , Menka Marivjena 
Published: February 2024

BackgroundMandatory joint police and healthcare investigations of sudden unexpected death in infancy (SUDI) have been in place since 2008 in England. These include death scene examination with cause of death determined at multiprofessional case conference. Detailed evidence on sleep arrangements is available for most cases potentially leading to more being identified as due to accidental suffocation. SUDI remaining unexplained following investigation are classified as SIDS (sudden infant death syndrome) or unspecified deaths.Our objective was to determine whether detailed SUDI investigation has led to an increase in deaths classified as accidental suffocation or strangulation in bed (ASSB)?MethodsWe obtained official mortality data for England and Wales for infants dying aged 0–364 days for International Statistical Classification of Diseases and Related Health Problems, 10th revision codes R95 (SIDS), R96, R98, R99 (unspecified causes of mortality) and W75 (ASSB) for the years 2000–2019.We calculated the mortality rate for ASSB, SIDS and unspecified causes based on total live births each year.ResultsUnexplained SUDI decreased from 353 in 2000 to 175 in 2019, with the mortality rate falling from 0.58 to 0.29 per 1000 live births. The total postneonatal mortality rate fell during this time from 1.9 to 0.9 per 1000 live births suggesting this is a genuine fall. SIDS accounted for 70% of unexplained SUDI in 2000 falling to 49% in 2020 with a corresponding increase in R99 unspecified deaths.Few deaths were recorded as ASSB (W75), ranging between 4 in 2010 and 24 in 2001. The rate for ASSB ranged from 0.6 to 4.0 per 100000 live births.ConclusionsThere is a shift away from SIDS (R95) towards unspecified causes of death (R96, R98, R99). Improved investigation of deaths has not led to increased numbers of death identified as due to ASSB. There needs to be clear guidelines on accurate classification of deaths from ASSB to facilitate learning from deaths and inform prevention efforts.
Nivolumab monotherapy or combination with ipilimumab with or without cobimetinib in previously treated patients with pancreatic adenocarcinoma (CheckMate 032)
Authors: Callahan Margaret , Amin Asim , Kaye Frederic J , Morse Michael A , Taylor Matthew H , Peltola Katriina J , Sharma Padmanee , O'Reilly Eileen M , Meadows Shropshire Stephanie , O'Brien Shaun , Tschaika Marina , Le Dung T 
Published: February 2024

BackgroundPancreatic cancer is one of the deadliest cancer types and represents a major unmet medical need. CheckMate 032 investigated safety and efficacy of nivolumab monotherapy and nivolumab plus ipilimumab with/without cobimetinib in advanced/metastatic solid tumors, including pancreatic cancer.MethodsIn the original pancreatic cancer cohort, previously treated patients (≥1 prior regimen) with advanced/metastatic pancreatic adenocarcinoma were assigned to nivolumab 3 mg/kg every 2 weeks (monotherapy arm) or nivolumab 1 mg/kg and ipilimumab 1 mg/kg or 3 mg/kg every 3 weeks for four doses, followed by nivolumab 3 mg/kg every 2 weeks (combination arm). A subsequent modified pancreatic cohort (one or two prior regimens) received nivolumab 3 mg/kg every 2 weeks, ipilimumab 1 mg/kg every 6 weeks, and cobimetinib 60 mg orally once daily for 21 days on and 7 days off (triplet arm). The primary endpoint was investigator-assessed objective response rate (ORR). Secondary endpoints were investigator-assessed progression-free survival (PFS), PFS rate, overall survival (OS), OS rate, safety, and tolerability. Additionally, ORR, PFS, and duration of response were assessed by blinded independent central review (BICR) in the triplet arm.Results18 patients received nivolumab monotherapy, 21 received nivolumab plus ipilimumab, and 30 received nivolumab plus ipilimumab plus cobimetinib. In the triplet arm, partial responses were observed in two patients per investigator (ORR 6.7% (95% CI 0.8% to 22.1%)) and in three patients per BICR (ORR 10% (95% CI 2.1% to 26.5%)); no responses were observed in the other arms. Median (95% CI) PFS per investigator was 1.4 (1.3 to 2.0), 1.4 (1.2 to 2.7), and 3.0 (1.5 to 4.1) months for the monotherapy, nivolumab plus ipilimumab, and triplet arms, respectively. Median (95% CI) OS was 5.1 (2.0 to 9.0) months, 4.0 (1.9 to 5.6) months, and 6.2 (3.9 to 11.4) months, respectively. Most treatment-related adverse events were grade 2 or less.ConclusionsNivolumab with or without ipilimumab did not elicit objective responses in previously treated patients with advanced pancreatic adenocarcinoma, although three confirmed partial responses and manageable safety were observed with cobimetinib-containing triplet therapy. The small sample size and differences in baseline disease-specific characteristics between arms limit interpretation of these results.
Polyploidy in Cancer: Causal Mechanisms, Cancer-Specific Consequences, and Emerging Treatments
Authors: Conway Patrick J. , Dao Jonathan , Kovalskyy Dmytro , Mahadevan Daruka , Dray Eloise 
Published: February 2024

Abstract
Drug resistance is the major determinant for metastatic disease and fatalities, across all cancers. Depending on the tissue of origin and the therapeutic course, a variety of biological mechanisms can support and sustain drug resistance. Although genetic mutations and gene silencing through epigenetic mechanisms are major culprits in targeted therapy, drug efflux and polyploidization are more global mechanisms that prevail in a broad range of pathologies, in response to a variety of treatments. There is an unmet need to identify patients at risk for polyploidy, understand the mechanisms underlying polyploidization, and to develop strategies to predict, limit, and reverse polyploidy thus enhancing efficacy of standard-of-care therapy that improve better outcomes. This literature review provides an overview of polyploidy in cancer and offers perspective on patient monitoring and actionable therapy.
Antibody–Drug Conjugate αEGFR-E-P125A Reduces Triple-negative Breast Cancer Vasculogenic Mimicry, Motility, and Metastasis through Inhibition of EGFR, Integrin, and FAK/STAT3 Signaling
Authors: Sankar Ankita P. , Cho Hyun-Mi , Shin Seung-Uon , Sneh Tal , Ramakrishnan Sundaram , Elledge Christian , Zhang Yu , Das Rathin , Gil-Henn Hava , Rosenblatt Joseph D. 
Published: February 2024

Abstract

Primary tumor growth and metastasis in triple-negative breast cancer (TNBC) require supporting vasculature, which develop through a combination of endothelial angiogenesis and vasculogenic mimicry (VM), a process associated with aggressive metastatic behavior in which vascular-like structures are lined by tumor cells. We developed αEGFR-E-P125A, an antibody-endostatin fusion protein that delivers a dimeric, mutant endostatin (E-P125A) payload that inhibits TNBC angiogenesis and VM in vitro and in vivo. To characterize the mechanisms associated with induction and inhibition of VM, RNA sequencing (RNA-seq) of MDA-MB-231-4175 TNBC cells grown in a monolayer (two-dimensional) was compared with cells plated on Matrigel undergoing VM [three-dimensional (3D)]. We then compared RNA-seq between TNBC cells in 3D and cells in 3D with VM inhibited by αEGFR-E-P125A (EGFR-E-P125A). Gene set enrichment analysis demonstrated that VM induction activated the IL6-JAK-STAT3 and angiogenesis pathways, which were downregulated by αEGFR-E-P125A treatment.
Correlative analysis of the phosphoproteome demonstrated decreased EGFR phosphorylation at Y1069, along with decreased phosphorylation of focal adhesion kinase Y397 and STAT3 Y705 sites downstream of α5β1 integrin. Suppression of phosphorylation events downstream of EGFR and α5β1 integrin demonstrated that αEGFR-E-P125A interferes with ligand-receptor activation, inhibits VM, and overcomes oncogenic signaling associated with EGFR and α5β1 integrin cross-talk.
In vivo, αEGFR-E-P125A treatment decreased primary tumor growth and VM, reduced lung metastasis, and confirmed the inhibition of signaling events observed in vitro. Simultaneous inhibition of EGFR and α5β1 integrin signaling by αEGFR-E-P125A is a promising strategy for the inhibition of VM, tumor growth, motility, and metastasis in TNBC and other EGFR-overexpressing tumors.

Significance:
αEGFR-E-P125A reduces VM, angiogenesis, tumor growth, and metastasis by inhibiting EGFR and α5β1 integrin signaling, and is a promising therapeutic agent for TNBC treatment, used alone or in combination with chemotherapy.
Impact of Antihypertensive Medication Changes After Renal Denervation Among Different Patient Groups: SPYRAL HTN-ON MED
Authors: Townsend Raymond R. , Ferdinand Keith C. , Kandzari David E. , Kario Kazuomi , Mahfoud Felix , Weber Michael A. , Schmieder Roland E. , Pocock Stuart , Tsioufis Konstantinos , David Shukri , Steigerwalt Susan , Walton Antony , Hopper Ingrid , Bertolet Barry , Sharif Faisal , Fengler Karl , Fahy Martin , Hettrick Douglas A. , Brar Sandeep , Böhm Michael 
Published: February 2024

BACKGROUND:
The SPYRAL HTN-ON MED (Global Clinical Study of Renal Denervation With the Symplicity Spyral Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications)trial showed significant office and nighttime systolic blood pressure (BP) reductions in patients with hypertension following renal denervation (RDN) compared with sham-control patients, despite similar 24-hour BP reductions. We compared antihypertensive medication and BP changes among prespecified subpopulations.

METHODS:
The multicenter, randomized, sham-controlled, blinded SPYRAL HTN-ON MED trial (n=337) evaluated BP changes after RDN compared with a sham procedure in patients with hypertension prescribed 1 to 3 antihypertensive drugs. Most patients (n=187; 54%) were enrolled outside the United States, while 156 (46%) US patients were enrolled, including 60 (18%) Black Americans.

RESULTS:

Changes in detected antihypertensive drugs were similar between RDN and sham group patients in the outside US cohort, while drug increases were significantly more common in the US sham group compared with the RDN group. Patients from outside the United States showed significant reductions in office and 24-hour mean systolic BP at 6 months compared with the sham group, whereas BP changes were similar between RDN and sham in the US cohort. Within the US patient cohort, Black Americans in the sham control group had significant increases in medication burden from baseline through 6 months (
P
=0.003) but not in the RDN group (
P
=0.44).

CONCLUSIONS:
Patients enrolled outside the United States had minimal antihypertensive medication changes between treatment groups and had significant office and 24-hour BP reductions compared with the sham group. Increased antihypertensive drug burden in the US sham cohort, especially among Black Americans, may have diluted the treatment effect in the combined trial population.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02439775.
“Special Newborn Care Unit” Quality Care Assessment Using SNCU Quality of Care Indices (SQCIs) at Aspirational Districts, Odisha, 2020-2022
Authors: Sahu Dayasis , Sahu Smitamayee , Godara Naresh R. , Subbarayalu Yayathee 
Published: February 2024

Introduction Special newborn care unit (SNCU) Quality of Care Indices (SQCIs) are specific indicators that help in assessing and evaluating the quality of care provided to newborns in SNCUs. Aims and Objectives The study described the quality of care at SNCUs in aspirational districts of Odisha by using 7 quality of care indices, 2020-2022. Materials and Methods We conducted a cross-sectional descriptive study on all newborns who received care at SNCUs of 10 aspirational districts in Odisha using the data from the SNCU online database for 2020-2022. Every quarter of the year, all the parameters were extracted and entered into an already designed spreadsheet. The 7 indices generated the SQCI score. We used MS Excel (2021) for data analysis. Results A total of 50,226 admissions were registered. Perinatal asphyxia caused the significant morbidity (14,421, 29%). Throughout the 12 quarters, composite SQCI showed satisfactory performance (0.59-0.66). Rational admission of all units was good, and their scores were 0.71 to 0.87. Mortality in normal weight babies showed good performance. The Low Birth Weight Admission Index score ranged from 0.22 to 0.30, that is, unsatisfactory performance. During 2020 to 2022, the overall composite SQCI score of the 10 SNCUs corresponded to satisfactory care (0.56-0.68). Conclusion SQCI is an essential tool for assessing the SNCU quality evaluation. It should be regularly used at the district level to enhance quality care. Health facilities’ preparedness for managing perinatal asphyxia is to be studied.
Effects of Patiromer and Sodium Zirconium Cyclosilicate on Blood Pressure in Rats with Chronic Kidney Disease
Authors: Li Lingyun , Budden Jeff , Quinn Carol Moreno , Bushinsky David 
Published: February 2024

Background Potassium-binders patiromer and sodium zirconium cyclosilicate (SZC) are approved to treat hyperkalaemia, which is frequently observed in chronic kidney disease (CKD). Elevated blood pressure (BP) is common in CKD, due in part to impaired sodium excretion. The effect of patiromer, which exchanges calcium for potassium and SZC, which exchanges sodium or hydrogen for potassium, on BP was assessed in a CKD rat model. Methods Thirty-six Sprague Dawley rats with 5/6 nephrectomy were randomised to three groups (n = 12/group) to receive 4 g/kg/day patiromer or SZC, or vehicle treatment, for 8 weeks. BP was determined by radiotelemetry and urinary protein and electrolytes were measured. Results At Week 8, systolic BP (sBP) increased in all groups; however, patiromer led to a lower mean (standard deviation) sBP than vehicle or SZC (141 [2.9] vs 158 [5.2] or 162 [6.1] mm Hg, respectively, both p < 0.001), with no difference in sBP between vehicle and SZC ( p = 0.08). Similar results were observed for diastolic BP. Serum potassium levels fell with SZC ( p < 0.02), but not vehicle or patiromer. Urine potassium decreased with both patiromer and SZC versus vehicle ( p < 0.01); urine sodium increased with SZC ( p < 0.01); and urine calcium increased with patiromer ( p < 0.01). Urine phosphorus decreased with patiromer ( p < 0.01) but increased with SZC ( p < 0.01). Patiromer resulted in less proteinuria than vehicle or SZC (both p < 0.017). Conclusions After 8 weeks, treatment with patiromer resulted in lower BP in rats than vehicle or SZC. Further studies are needed to determine the mechanism of the differential effect of potassium binders on rat BP.
The Implication of Growth Arrest-Specific 5 rs145204276 Polymorphism and Serum Expression of Sirtuin 1, Transforming Growth Factor-Beta, and microRNA-182 in Breast Cancer
Authors: Hasona Nabil A , Elsabahy Mahmoud , Shaker Olfat G , Zaki Othman , Ayeldeen Ghada 
Published: February 2024

Background: Breast cancer (BC) patients have a higher chance of survival if it is diagnosed at an early stage, which is essential for efficient treatment of the condition. The results of an elevated risk of cancer, including BC, previously associated with the ins/del polymorphism rs145204276 in the promoter region of growth arrest-specific 5 (GAS5) are still up for debate. Thus, this study aimed to appraise the frequency of the GAS5 rs145204276 variant with BC risk and demonstrate the potential impact of the sirtuin 1 (SIRT-1), transforming growth factor-beta (TGF-β), and microRNA-182 (miR-182) expression and their diagnostic value in BC. Methods: Blood samples of 155 patients with BC and fibroadenoma and 80 healthy controls were analyzed for GAS5 rs145204276 single nucleotide polymorphism (SNP), SIRT-1, TGF-β, and miRNA-182 expression levels. Results: Ins/ins genotype and ins allele frequencies for GAS5 rs145204276 were considerably higher in BC patients compared with controls. Patients with BC had significantly greater serum levels of TGF-β, miR-182, and SIRT-1 expression. Conclusions: The SIRT-1, TGF-β, and miR-182 genes provide novel, noninvasive diagnostic biomarkers for BC.
Risk Factors for Distant Metastasis in T3 T4 Rectal Cancer
Authors: Tang Cui , Xu Jinming , Lin Moubin , Qiu Shixiong , Wang Huan , Zuo Xiaoming , Liu Mengxiao , Wang Peijun 
Published: February 2024

Background: Distant metastasis is the leading cause of death in patients with rectal cancer. This study aims to comprehensively analyze the risk factors of distant metastasis in T3 T4 rectal cancer using magnetic resonance imaging (MRI), pathological features, and serum indicators. Methods: The clinicopathological data of 146 cases of T3 T4 rectal cancer after radical resection from January 2015 to March 2023 were retrospectively analyzed. Pre- and postoperative follow-up data of all cases were collected to screen for distant metastatic lesions. Univariate and multivariate Logistic regression methods were used to analyze the relationship between MRI features, pathological results, serum test indexes, and distant metastasis. Results: Of the 146 included patients, synchronous or metachronous distance metastasis was confirmed in 43 (29.4%) cases. The patients’ baseline data and univariate analysis showed that mrEMVI, maximum tumor diameter, mr T Stage, pathological N stage, number of lymph node metastasis, cancer nodules, preoperative serum CEA, (Carcinoembryonic antigen) and CA199 were associated with distant metastasis. In the multiple logistic regression model, mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter, and preoperative serum CEA were identified as independent risk factors for distant metastasis: mrEMVI [odds ratio (OR) = 3.06], pathological N stage (OR = 6.52 for N1 vs N0; OR = 63.47 for N2 vs N0), preoperative serum CEA (OR = 0.27), tumor maximum diameter (OR = 1.03), number of lymph nodes metastasis (OR = 0.62). And, the receiver operating characteristic (ROC) curve was plotted and the area under the curve was calculated (area under the curve [AUC) = 0.817, 95% CI = 0.744-0.890, P < .001]. Conclusions: mrEMVI, pathological N stage, number of lymph node metastasis, maximum tumor diameter and preoperative serum CEA are the independent risk factors for distant metastasis in T3 T4 rectal cancer. A comprehensive analysis of the risk factors for distant metastasis in rectal cancer can provide a reliable basis for formulating individualized treatment strategies, follow-up plans, and evaluating prognosis.
Effectiveness of immunotherapies in relapsing myelin oligodendrocyte glycoprotein antibody-associated disease
Authors: Bilodeau Philippe Antoine , Vishnevetsky Anastasia , Molazadeh Negar , Lotan Itay , Anderson Monique , Romanow Gabriela , Salky Rebecca , Healy Brian C , Matiello Marcelo , Chitnis Tanuja , Levy Michael 
Published: February 2024

Background: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) can cause optic neuritis, transverse myelitis, or acute disseminated encephalomyelitis (ADEM). Immunotherapy is often used for relapsing disease, but there is variability in treatment decisions. Objective: The objective was to determine the annualized relapse rates (ARRs) and incidence rate ratios (IRRs) compared to pre-treatment and relapse-freedom probabilities among patients receiving steroids, B-cell depletion (BCD), intravenous immunoglobulin (IVIG), and mycophenolate mofetil (MMF). Methods: Retrospective cohort study of patients with relapsing MOGAD treated at Mass General Brigham. ARRs and IRRs compared to pre-treatment, and relapse-freedom probability and odds ratio for relapse-freedom compared to prednisone were calculated. Results: A total of 88 patients met the inclusion criteria. The ARR on IVIG was 0.13 (95% confidence interval (CI) = 0.06–0.27) and the relapse-freedom probability after at least 6 months of therapy was 72%. The ARR on BCD was 0.51 (95% CI = 0.34–0.77), and the relapse-freedom probability was 33%. The ARR on MMF was 0.32 (95% CI = 0.19–0.53) and the relapse-freedom probability was 49%. In pediatric-onset disease, MMF had the lowest ARRs (0.15, 95% CI = 0.07–0.33). Conclusion: IVIG had the lowest ARRs and IRRs compared to pre-treatment and the highest relapse-freedom odds ratio compared to prednisone, while BCD had the lowest. In pediatric-onset MOGAD, MMF had the lowest ARRs.
Assessment of adjacent building vibrations induced by metro with a multigrid fully coupled method
Authors: Wang Qihao , Cai Xiaopei , Qi Yanli , Zhang Qian , Tang Xueyang 
Published: February 2024

The vibrations generated by metro operations can cause structural damage and discomfort to occupants adjacent to the metro lines. In this study, a multigrid fully coupled method of metro vehicle-track-station-soil-building systems is proposed to predict and assess building vibrations before construction. This approach facilitates the efficient calculation of the fully coupled system, while ensuring precise simulations through the utilization of multigrid techniques for wheel-rail contact, track, station, soil, and building components. Using the newly built opera theatre along Beijing metro line 4 as a case, the study demonstrates that the multigrid fully coupled model can predict the dynamics characteristics of metro-induced vibrations and distribution with high accuracy compared with the field tests. Specifically, it was found that metro operations could result in vibrations exceeding specified limits in the opera theatre, particularly at 10∼40 Hz (the building’s natural frequency) and 60∼80 Hz (the main frequency band of vibration caused by the metro). Finally, the mechanism of excessive vibration and the effectiveness of targeted vibration mitigation measures were analyzed with the proposed method. These findings have promising implications for wider applications in environmental assessments and control strategies for new metro lines or vibration-sensitive buildings.