bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mixed-methods study measuring the effectiveness of a menstrual health intervention on menstrual health knowledge, perceptions and practices among young women in Zimbabwe
Authors: Tembo Mandikudza , Weiss Helen A , Larsson Leyla Sophie , Bandason Tsitsi , Redzo Nicol , Dauya Ethel , Nzanza Tafadzwa , Ishumael Pauline , Gweshe Nancy , Ndlovu Precious , Dziva Chikwari Chido , Mavodza Constancia Vimbayi , Renju Jenny , Francis Suzanna C , Ferrand Rashida , Mackworth-Young Constance R S 
Published: March 2023

ObjectivesWhile integral to women’s physical and mental well-being, achieving good menstrual health (MH) remains a challenge for many women. This study investigated the effectiveness of a comprehensive MH intervention on menstrual knowledge, perceptions and practices among women aged 16–24 years in Harare, Zimbabwe.DesignA mixed-methods prospective cohort study with pre-post evaluation of an MH intervention.SettingTwo intervention clusters in Harare, Zimbabwe.ParticipantsOverall, 303 female participants were recruited, of whom 189 (62.4%) were seen at midline (median follow-up 7.0; IQR 5.8–7.7 months) and 184 (60.7%) were seen at endline (median follow-up 12.4; IQR 11.9–13.8 months). Cohort follow-up was greatly affected by COVID-19 pandemic and associated restrictions.InterventionThe MH intervention provided MH education and support, analgesics, and a choice of menstrual products in a community-based setting to improve MH outcomes among young women in Zimbabwe.Primary and secondary outcomesEffectiveness of a comprehensive MH intervention on improving MH knowledge, perceptions, and practices among young women over time. Quantitative questionnaire data were collected at baseline, midline, and endline. At endline, thematic analysis of four focus group discussions was used to further explore participants’ menstrual product use and experiences of the intervention.ResultsAt midline, more participants had correct/positive responses for MH knowledge (adjusted OR (aOR)=12.14; 95% CI: 6.8 to 21.8), perceptions (aOR=2.85; 95% CI: 1.6 to 5.1) and practices for reusable pads (aOR=4.68; 95% CI: 2.3 to 9.6) than at baseline. Results were similar comparing endline with baseline for all MH outcomes. Qualitative findings showed that sociocultural norms, stigma and taboos around menstruation, and environmental factors such as limited access to water, sanitation and hygiene facilities affected the effect of the intervention on MH outcomes.ConclusionsThe intervention improved MH knowledge, perceptions and practices among young women in Zimbabwe, and the comprehensive nature of the intervention was key to this. MH interventions should address interpersonal, environmental and societal factors.Trial registration numberNCT03719521.
Efficacy and safety of acupuncture for postpartum hypogalactia: protocol for a systematic review and meta-analysis
Authors: Bao Qiong-Nan , Zhou Yuan-Fang , Yin Zi-Han , Bi Qiu , Zhao Hong-Bin , Zhang Zhen-Yong , Liang Fan-Rong 
Published: March 2023

IntroductionBreast milk is recognised as the best natural food for neonates, but many women experience postpartum hypogalactia (PH). Randomised trials have found that acupuncture exert therapeutic effect on women with PH. However, systematic reviews on the efficacy and safety of acupuncture are still lacking; therefore, this systematic review aims to evaluate the efficacy and safety of acupuncture for PH.Methods and analysisSix English databases (PubMed, Cochrane Library, EMBASE, EBSCO, Scopus, and Web of Science) and four Chinese databases (China National Knowledge Infrastructure, Wan-Fang, Chinese Biomedical Literature and Chinese Scientific Journal) will be systematically searched from their establishment to 1 September 2022. Randomised controlled trials of the efficacy of acupuncture for PH will be reviewed. The study selection, data extraction and research quality evaluation will be conducted independently by two reviewers. The primary outcome is the change in serum prolactin level from baseline to the end of treatment. Secondary results include milk secretion volume, total effectiveness rate, degree of mammary fullness, rate of exclusive breast feeding, and adverse events. A meta-analysis will be performed using RevMan V.5.4 statistical software. Otherwise, a descriptive analysis will be conducted. The risk of bias will be assessed using the revised Cochrane risk-of-bias tool.Ethics and disseminationThis systematic review protocol does not require ethical approval because it does not include private information/data of the participants. This article will be published in peer-reviewed journals.PROSPERO registration numberCRD42022351849.
A prospective, comparative study of clinical outcomes following clinic-based versus self-use of medical abortion
Authors: Kapp Nathalie , Mao Bunsoth , Menzel Jamie , Eckersberger Elisabeth , Saphonn Vonthanak , Rathavy Tung , Pearson Erin 
Published: March 2023

BackgroundTo determine whether clinical outcomes differ among women accessing a combined medical abortion regimen from a health clinic when compared with those accessing it from a pharmacy.MethodsWe conducted a multicentre, prospective, comparative, non-inferiority study of participants aged ≥15 years seeking medical abortion from five clinics and five adjacent pharmacy clusters in three provinces of Cambodia. Participants were recruited in-person at the point of purchase (clinic or pharmacy). Follow-up for self-reported pill use, acceptability, and clinical outcomes occurred by telephone at days 10 and 30 after mifepristone administration.ResultsOver 10 months, we enrolled 2083 women with 1847 providing outcome data: 937 from clinics and 910 from pharmacies. Most were early in their pregnancy (mean gestational age of 6.3 and 6.1 weeks, respectively) and almost all took the pills correctly (98% and 96%,). Additional treatment needed to complete the abortion was non-inferior for the pharmacy group (9.3%) compared with the clinic group (12.7%). More from the clinic group received additional care from a provider, such as antibiotics or diagnostics tests, than those from the pharmacy group (11.5% and 3.2%,), and one ectopic pregnancy (pharmacy group) was successfully treated. Most said they felt prepared for what happened after taking the pills (90.9% and 81.3%, respectively, p=0.273).ConclusionsSelf-use of a combined medical abortion product resulted in comparable clinical outcomes as use following a clinical visit, consistent with existing literature on its safety and efficacy. Registration and availability of medical abortion as an over-the-counter product would likely increase women’s access to safe abortion.
ASS1-Mediated Reductive Carboxylation of Cytosolic Glutamine Confers Ferroptosis Resistance in Cancer Cells
Authors: Hu Qiangsheng , Dai Jie , Zhang Zheng , Yu Huansha , Zhang Jing , Zhu Xinsheng , Qin Yi , Zhang Lele , Zhang Peng 
Published: March 2023

Abstract

Induction of ferroptosis, a recently defined form of nonapoptotic cell death caused by iron-dependent lipid peroxidation, has emerged as an anticancer strategy. Erastin is a ferroptosis activator that promotes cell death that not only depends on the depletion of cellular cysteine but also relies on mitochondrial oxidative metabolism of glutamine. Here, we demonstrate that ASS1, a key enzyme involved in the urea cycle, plays a crucial role in ferroptosis resistance. Loss of ASS1 increased the sensitivity of non–small cell lung cancer (NSCLC) cells to erastin in vitro and decreased tumor growth in vivo. Metabolomics analysis with stable isotope-labeled glutamine showed that ASS1 promotes reductive carboxylation of cytosolic glutamine and compromises the oxidative tricarboxylic acid cycle from glutamine anaplerosis, reducing mitochondrial-derived lipid reactive oxygen species. Moreover, transcriptome sequencing showed that ASS1 activates the mTORC1–SREBP1–SCD5 axis to promote de novo monounsaturated fatty acid synthesis by using acetyl-CoA derived from the glutamine reductive pathway. Treating ASS1-deficient NSCLC cells with erastin combined with arginine deprivation significantly enhanced cell death compared with either treatment alone. Collectively, these results reveal a previously unknown regulatory role of ASS1 in ferroptosis resistance and provide a potential therapeutic target for ASS1-deficient NSCLC.

Significance:
ASS1 promotes reductive carboxylation of glutamine and confers ferroptosis resistance, providing multiple treatment options for ASS1-deficient non–small cell lung cancer.
The Oncolytic Adenovirus XVir-N-31 Joins Forces with CDK4/6 Inhibition Augmenting Innate and Adaptive Antitumor Immunity in Ewing Sarcoma
Authors: Schober Sebastian Johannes , Schoening Caroline , Eck Jennifer , Middendorf Charlotte , Lutsch Julia , Knoch Pia , von Ofen Anna Josefine , Gassmann Hendrik , Thiede Melanie , Hauer Julia , Kolk Andreas , Mantwill Klaus , Gschwend Jürgen E. , Burdach Stefan E.G. , Nawroth Roman , Thiel Uwe , Holm Per Sonne 
Published: March 2023

Abstract

Purpose:
Ewing sarcoma (EwS) is a highly malignant pediatric tumor characterized by a non-T-cell-inflamed immune-evasive phenotype. When relapsed or metastasized, survival is poor, emphasizing the need for novel treatment strategies. Here, we analyze the novel combination approach using the YB-1-driven oncolytic adenovirus XVir-N-31 and CDK4/6 inhibition to augment EwS immunogenicity.

Experimental Design:
In vitro, viral toxicity, replication, and immunogenicity were studied in several EwS cell lines. In vivo tumor xenograft models with transient humanization were applied to evaluate tumor control, viral replication, immunogenicity, and dynamics of innate as well as human T cells after treatment with XVir-N-31 combined with CDK4/6 inhibition. Furthermore, immunologic features of dendritic cell maturation and T-cell-stimulating capacities were assessed.

Results:
The combination approach significantly increased viral replication and oncolysis in vitro, induced HLA-I upregulation, and IFNγ-induced protein 10 expression and enhanced maturation of monocytic dendritic cells with superior capacities to stimulate tumor antigen-specific T cells. These findings were confirmed in vivo showing tumor infiltration by (i) monocytes with antigen-presenting capacities and M1 macrophage marker genes, (ii) TReg suppression in spite of adenovirus infection, (iii) superior engraftment, and (iv) tumor infiltration by human T cells. Consequently, survival was improved over controls with signs of an abscopal effect after combination treatment.

Conclusions:
The joint forces of the YB-1-driven oncolytic adenovirus XVir-N-31 and CDK4/6 inhibition induce therapeutically relevant local and systemic antitumor effects. Innate as well as adaptive immunity against EwS is boosted in this preclinical setting, pointing toward high therapeutic potential in the clinic.
Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma
Authors: Schoen Robert E. , Boardman Lisa A. , Cruz-Correa Marcia , Bansal Ajay , Kastenberg David , Hur Chin , Dzubinski Lynda , Kaufman Sharon F. , Rodriguez Luz M. , Richmond Ellen , Umar Asad , Szabo Eva , Salazar Andres , McKolanis John , Beatty Pamela , Pai Reetesh K. , Singhi Aatur D. , Jacqueline Camille M. , Bao Riyue , Diergaarde Brenda , McMurray Ryan P. , Strand Carrie , Foster Nathan R. , Zahrieh David M. , Limburg Paul J. , Finn Olivera J. 
Published: March 2023

AbstractPurpose:To assess whether MUC1 peptide vaccine produces an immune response and prevents subsequent colon adenoma formation.Patients and Methods:Multicenter, double-blind, placebo-controlled randomized trial in individuals age 40 to 70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0.Results:Fifty-three participants received the MUC1 vaccine and 50 placebo. Thirteen of 52 (25%) MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range, 2.9–17.3) at week 12 versus 0/50 placebo recipients (one-sided Fisher exact P &lt; 0.0001). Of 13 responders at week 12, 11 (84.6%) responded to a booster injection at week 52 with a ≥2-fold increase in MUC1 IgG measured at week 55. Recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group versus 27 of 48 (56.3%) in the MUC1 group [adjusted relative risk (aRR), 0.83; 95% confidence interval (CI), 0.60–1.14; P = 0.25]. Adenoma recurrence occurred in 3/11 (27.3%) immune responders at week 12 and week 55 (aRR, 0.41; 95% CI, 0.15–1.11; P = 0.08 compared with placebo). There was no difference in serious adverse events.Conclusions:An immune response was observed only in vaccine recipients. Adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence compared with placebo was observed in participants who had an immune response at week 12 and with the booster injection.
Combinatorial BCL2 Family Expression in Acute Myeloid Leukemia Stem Cells Predicts Clinical Response to Azacitidine/Venetoclax
Authors: Waclawiczek Alexander , Leppä Aino-Maija , Renders Simon , Stumpf Karolin , Reyneri Cecilia , Betz Barbara , Janssen Maike , Shahswar Rabia , Donato Elisa , Karpova Darja , Thiel Vera , Unglaub Julia M. , Grabowski Susanna , Gryzik Stefanie , Vierbaum Lisa , Schlenk Richard F. , Röllig Christoph , Hundemer Michael , Pabst Caroline , Heuser Michael , Raffel Simon , Müller-Tidow Carsten , Sauer Tim , Trumpp Andreas 
Published: March 2023

Abstract

The BCL2 inhibitor venetoclax (VEN) in combination with azacitidine (5-AZA) is currently transforming acute myeloid leukemia (AML) therapy. However, there is a lack of clinically relevant biomarkers that predict response to 5-AZA/VEN. Here, we integrated transcriptomic, proteomic, functional, and clinical data to identify predictors of 5-AZA/VEN response. Although cultured monocytic AML cells displayed upfront resistance, monocytic differentiation was not clinically predictive in our patient cohort. We identified leukemic stem cells (LSC) as primary targets of 5-AZA/VEN whose elimination determined the therapy outcome. LSCs of 5-AZA/VEN-refractory patients displayed perturbed apoptotic dependencies. We developed and validated a flow cytometry-based “Mediators of apoptosis combinatorial score” (MAC-Score) linking the ratio of protein expression of BCL2, BCL-xL, and MCL1 in LSCs. MAC scoring predicts initial response with a positive predictive value of more than 97% associated with increased event-free survival. In summary, combinatorial levels of BCL2 family members in AML-LSCs are a key denominator of response, and MAC scoring reliably predicts patient response to 5-AZA/VEN.

Significance:
Venetoclax/azacitidine treatment has become an alternative to standard chemotherapy for patients with AML. However, prediction of response to treatment is hampered by the lack of clinically useful biomarkers. Here, we present easy-to-implement MAC scoring in LSCs as a novel strategy to predict treatment response and facilitate clinical decision-making.
This article is highlighted in the In This Issue feature, p. 1275
Platelet-Derived MicroRNAs Regulate Cardiac Remodeling After Myocardial Ischemia
Authors: Schütte Jan Philipp , Manke Mailin-Christin , Hemmen Katherina , Münzer Patrick , Schörg Barbara F. , Ramos Gustavo Campos , Pogoda Michaela , Dicenta Valerie , Hoffmann Sabrina H.L. , Pinnecker Jürgen , Kollotzek Ferdinand , Zdanyte Monika , Mueller Karin A.L. , Singh Yogesh , Mack Andreas F. , Pichler Bernd , Lang Florian , Nieswandt Bernhard , Gawaz Meinrad , Heinze Katrin G. , Casadei Nicolas , Borst Oliver 
Published: March 2023

Background:
Platelets can infiltrate ischemic myocardium and are increasingly recognized as critical regulators of inflammatory processes during myocardial ischemia and reperfusion (I/R). Platelets contain a broad repertoire of microRNAs (miRNAs), which, under certain conditions such as myocardial ischemia, may be transferred to surrounding cells or released into the microenvironment. Recent studies could demonstrate that platelets contribute substantially to the circulating miRNA pool holding the potential for so far undiscovered regulatory functions. The present study aimed to determine the role of platelet-derived miRNAs in myocardial injury and repair following myocardial I/R.

Methods:
In vivo model of myocardial I/R, multimodal in vivo and ex vivo imaging approaches (light-sheet fluorescence microscopy, positron emission tomography and magnetic resonance imaging, speckle-tracking echocardiography) of myocardial inflammation and remodeling, and next-generation deep sequencing analysis of platelet miRNA expression.

Results:

In mice with a megakaryocyte/platelet-specific knockout of pre-miRNA processing ribonuclease
Dicer
, the present study discloses a key role of platelet-derived miRNAs in the tightly regulated cellular processes orchestrating left ventricular remodeling after myocardial I/R following transient left coronary artery ligation. Disruption of the miRNA processing machinery in platelets by deletion of
Dicer
resulted in increased myocardial inflammation, impaired angiogenesis, and accelerated development of cardiac fibrosis, culminating in an increased infarct size by d7 that persisted through d28 of myocardial I/R. Worsened cardiac remodeling after myocardial infarction in mice with a platelet-specific
Dicer
deletion resulted in an increased fibrotic scar formation and distinguishably increased perfusion defect of the apical and anterolateral wall at day 28 post-myocardial infarction. Altogether, these observations culminated in an impaired left ventricular function and hampered long-term cardiac recovery after experimental myocardial infarction and reperfusion therapy. Treatment with the P2Y
12
(P2Y purinoceptor 12) antagonist ticagrelor completely reversed increased myocardial damage and adverse cardiac remodeling observed in

Dicer
Pf4∆/Pf4∆

mice.

Conclusions:
The present study discloses a critical role of platelet-derived miRNA in myocardial inflammation and structural remodeling processes following myocardial I/R.
Arrhythmogenic Cardiotoxicity Associated With Contemporary Treatments of Lymphoproliferative Disorders
Authors: Sherazi Saadia , Schleede Susan , McNitt Scott , Casulo Carla , Moore Jeremiah E. , Storozynsky Eugene , Patel Arpan , Vidula Neelima , Aktas Mehmet K. , Zent Clive S. , Goldenberg Ilan 
Published: March 2023

Background
There are limited data on risk of arrhythmias among patients with lymphoproliferative disorders. We designed this study to determine the risk of atrial and ventricular arrhythmia during treatment of lymphoma in a real‐world setting.

Methods and Results

The study population comprised 2064 patients included in the University of Rochester Medical Center Lymphoma Database from January 2013 to August 2019. Cardiac arrhythmias—atrial fibrillation/flutter, supraventricular tachycardia, ventricular arrhythmia, and bradyarrhythmia—were identified using
International Classification of Diseases, Tenth Revision
(
ICD‐10
) codes. Multivariate Cox regression analysis was used to assess the risk of arrhythmic events with treatments categorized as Bruton tyrosine kinase inhibitor (BTKi), mainly ibrutinib/non‐BTKi treatment versus no treatment. Median age was 64 (54–72) years, and 42% were women. The overall rate of any arrhythmia at 5 years following the initiation of BTKi was (61%) compared with (18%) without treatment. Atrial fibrillation/flutter was the most common type of arrhythmia accounting for 41%. Multivariate analysis showed that BTKi treatment was associated with a 4.3‐fold (
P
<0.001) increased risk for arrhythmic event (
P
<0.001) compared with no treatment, whereas non‐BTKi treatment was associated with a 2‐fold (
P
<0.001) risk increase. Among subgroups, patients without a history of prior arrhythmia exhibited a pronounced increase in the risk for the development of arrhythmogenic cardiotoxicity (3.2‐fold;
P
<0.001).

Conclusions
Our study identifies a high burden of arrhythmic events after initiation of treatment, which is most pronounced among patients treated with the BTKi ibrutinib. Patients undergoing treatments for lymphoma may benefit from prospective focused cardiovascular monitoring prior, during, and after treatment regardless of arrhythmia history.
Serum Pro‐N‐Cadherin Is a Marker of Subclinical Heart Failure in the General Population
Authors: Ferrell Paul Durham , Oristian Kristianne Michelle , Puranam Ishaan , Pizzo Salvatore Vincent 
Published: March 2023

Background
We recently reported aberrant processing and localization of the precursor PNC (pro‐N‐cadherin) protein in failing heart tissues and detected elevated PNC products in the plasma of patients with heart failure. We hypothesize that PNC mislocalization and subsequent circulation is an early event in the pathogenesis of heart failure, and therefore circulating PNC is an early biomarker of heart failure.

Methods and Results

In collaboration with the Duke University Clinical and Translational Science Institute's MURDOCK (Measurement to Understand Reclassification of Disease of Cabarrus and Kannapolis) study, we queried enrolled individuals and sampled 2 matched cohorts: a cohort of individuals with no known heart failure at the time of serum collection and no heart failure development in the following 13 years (n=289, cohort A) and a matching cohort of enrolled individuals who had no known heart failure at the time of serum collection but subsequently developed heart failure within the following 13 years (n=307, cohort B). Serum PNC and NT‐proBNP (N‐terminal pro B‐type natriuretic peptide) concentrations in each population were quantified by ELISA. We detected no significant difference in NT‐proBNP rule‐in or rule‐out statistics between the 2 cohorts at baseline. In participants who developed heart failure, serum PNC is significantly elevated relative to those who did not report development of heart failure (
P
<0.0001). Receiver operating characteristic analyses of PNC demonstrate diagnostic value for subclinical heart failure. Additionally, PNC has diagnostic potential when comparing participants with no reported heart failure risk factors from cohort A to at‐risk participants from cohort B over the 13‐year follow‐up. Participants whose PNC levels measure >6 ng/mL have a 41% increased risk of all‐cause mortality independent of age, body mass index, sex, NT‐proBNP, blood pressure, previous heart attack, and coronary artery disease (
P
=0.044, n=596).

Conclusions
These data suggest that PNC is an early marker of heart failure and has the potential to identify patients who would benefit from early therapeutic intervention.