bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conventional Vasopressor and Vasopressor‐Sparing Strategies to Counteract the Blood Pressure–Lowering Effect of Small Interfering RNA Targeting Angiotensinogen
Authors: Uijl Estrellita , Ye Dien , Ren Liwei , Mirabito Colafella Katrina M. , van Veghel Richard , Garrelds Ingrid M. , Lu Hong S. , Daugherty Alan , Hoorn Ewout J. , Nioi Paul , Foster Don , Danser A. H. Jan 
Published: July 2022

Background
A single dose of small interfering RNA (siRNA) targeting liver angiotensinogen eliminates hepatic angiotensinogen and lowers blood pressure. Angiotensinogen elimination raises concerns for clinical application because an angiotensin rise is needed to maintain perfusion pressure during hypovolemia. Here, we investigated whether conventional vasopressors can raise arterial pressure after angiotensinogen depletion.

Methods and Results
Spontaneously hypertensive rats on a low‐salt diet were treated with siRNA (10 mg/kg fortnightly) for 4 weeks, supplemented during the final 2 weeks with fludrocortisone (6 mg/kg per day), the α‐adrenergic agonist midodrine (4 mg/kg per day), or a high‐salt diet (all groups n=6–7). Pressor responsiveness to angiotensin II and norepinephrine was assessed before and after siRNA administration. Blood pressure was measured via radiotelemetry. Depletion of liver angiotensinogen by siRNA lowered plasma angiotensinogen concentrations by 99.2±0.1% and mean arterial pressure by 19 mm Hg. siRNA‐mediated blood pressure lowering was rapidly reversed by intravenous angiotensin II or norepinephrine, or gradually reversed by fludrocortisone or high salt intake. Midodrine had no effect. Unexpectedly, fludrocortisone partially restored plasma angiotensinogen concentrations in siRNA‐treated rats, and nearly abolished plasma renin concentrations. To investigate whether this angiotensinogen originated from nonhepatic sources, fludrocortisone was administered to mice lacking hepatic angiotensinogen. Fludrocortisone did not increase angiotensinogen in these mice, implying that the rise in angiotensinogen in the siRNA‐treated rats must have depended on the liver, most likely reflecting diminished cleavage by renin.

Conclusions
Intact pressor responsiveness to conventional vasopressors provides pharmacological means to regulate the blood pressure–lowering effect of angiotensinogen siRNA and may support future therapeutic implementation of siRNA.
Assessing Raindrop Breakup Parameterizations Using Disdrometer Observations
Authors: Saleeby Stephen M. , Dolan Brenda , Bukowski Jennie , Van Valkenburg Kristen , van den Heever Susan C. , Rutledge Steven A. 
Published: July 2022

Abstract
An intercomparison of raindrop mean diameter frequency distribution (RDFD) is performed for numerical simulations of precipitating cloud systems using an array of models and microphysics schemes. This includes results from the Regional Atmospheric Modeling System (RAMS) double-moment microphysics, the Hebrew University Cloud Model bin microphysics (HUCM) interfaced to the RAMS parent model, and the Weather Research and Forecasting (WRF) Model with the Thompson, Morrison, double-moment 6-class (WDM6), and National Severe Storms Laboratory (NSSL) double-moment schemes. Simulations are examined with respect to the raindrop size distribution (DSD) volume-number mean diameter (Dm) and intercept parameter (Nw). When compared to a suite of disdrometer observations, the RDFD resulting from each microphysics scheme exhibits varying degrees of mean drop size constraints and peaks in the frequency distribution of Dm. A more detailed investigation of the peaked RDFD from the RAMS simulations suggests that the parameterization of raindrop collisional breakup can impose strong limitations on the evolution of simulated drop growth. As such, a summary and comparison of the drop breakup parameterizations among the aforementioned microphysics schemes is presented. While some drop breakup parameterizations are adjusted toward the observations by modifying the threshold diameter for the onset of breakup, this study explores the use of a modified maximum breakup efficiency. This method permits the parameterization to retain its threshold breakup diameter, while limiting the strength of drop breakup and permitting a broader range of drop sizes. As a result, the simulated mean drop sizes are in better agreement with observations.
Dynamical Mechanism of the Summer Circulation Trend Pattern and Surface High Temperature Anomalies over the Russian Far East
Authors: Kim Dong Wan , Lee Sukyoung 
Published: July 2022

Abstract
This study investigates the mechanism behind the recent boreal summer circulation trend pattern and associated high surface temperature anomalies over the Russian Far East. This circulation pattern includes a prominent anticyclone over the Kamchatka Peninsula where heat extremes have been trending upward. Observational analysis and numerical model simulations indicate that latent heating anomalies centered over Yakutia, west of Kamchatka Peninsula, can excite this anticyclone and the downstream circulation trend pattern. However, this anticyclone alone is insufficient for generating the anomalously high temperature over the region. Instead, the high temperature emerges when there is an upstream precursor that resembles the Eurasian circulation trend pattern. Warm advection by this upstream circulation initiates a positive temperature anomaly over the Russian Far East, one week prior to the onset of the anticyclone in this region. As this anticyclone develops, the temperature anomalies further intensify by adiabatic warming and shortwave radiative heating. If upstream circulation anomalies are opposite to those of the Eurasian trend pattern, the initial temperature over the Russian Far East is anomalously negative. As a result, the adiabatic warming and shortwave radiative heating within this anticyclonic region are unable to bring the temperature to an extreme condition. These findings indicate that the temperature extremes over the Russian Far East are contributed by a combination of remote and local circulation forcings and provide insights into subseasonal forecasts of heat waves over this region.
The bipolar patients’ family experiences of the outcomes of encountering stigma in Tehran: A qualitative study
Authors: Latifian Maryam , Raheb Ghoncheh , Abdi Kianoush , Alikhani Rosa 
Published: July 2022

Introduction: Nowadays, the most common psychological-social pressure to which bipolar patients’ families are exposed is stigma. Therefore, the present study was conducted to delve into the bipolar patients’ family experiences of the outcomes of encountering stigma. Method: The study was of qualitative type. Purposive sampling was used to select the participants from the persons suffering from bipolar disorder and their families. Twenty seven of the participants were interviewed. The main data collection instrument was semi-structured interview with open questions. Additionally, the collected data were analyzed via inductive content analysis method. The accuracy and validity of the study rooted in four factors: credibility, transferability, verifiability, and reliability. Results: Data analysis led to 1,326 primary codes, which were further categorized into five main categories as the main outcomes of encountering stigma (social deprivation, emotional and sentimental excitement, objective and behavioral reflections, family solidarity threat, and separation from society) and 21 sub-categories. Conclusion: Given then irreparable outcomes of stigma for bipolar patients’ family, it is necessary to take it into consideration. It is recommended to use media and also hygienic-treatment centers to educate different levels of society as to appropriate treatment with these patients and their families.
Food insecurity and medication restricting behavior among persons with diabetes in the United States
Authors: McClintock Heather F. , Imel Brittany E. 
Published: July 2022

Background Medication restricting behaviours are common among persons with diabetes increasing risk for poor health outcomes. Persons with diabetes are more likely to experience food insecurity than persons without diabetes. Aim This study aimed to assess the relationship between food insecurity and medication restricting behaviour among persons with diabetes in the United States. Methods Data from the 2019 National Health Interview Survey (NHIS) data conducted in the United States was used for this analysis. Medication restricting behaviour was assessed by questions asking whether four restricting behaviours were present (skipped medication, took less medication, delayed filling a prescription and/or took less medication due to cost). Food insecurity status was obtained through a 10-item scale and participants were categorized as either food secure, low food security, or very low food security. Poisson regression evaluated the relationship between medication restricting behaviour and food insecurity controlling for confounders. Results Participants with very low food security had a significantly higher mean number of medication restricting behaviours than participants who were food secure (adjusted mean ratio (AMR) = 4.01; 95% confidence interval (CI) = (3.09, 5.21)). Similarly, participants with low food security had a significantly higher mean ratio than participants who were food secure (AMR = 3.76; 95% CI = (2.86. 4.94). Conclusion Persons with diabetes who have low or very low food security are at an increased risk for engaging in medication restricting behaviours.
Reproducibility of pulmonary magnetic resonance angiography in adults with muco-obstructive pulmonary disease
Authors: Wucherpfennig Lena , Triphan Simon MF , Weinheimer Oliver , Eichinger Monika , Wege Sabine , Eberhardt Ralf , Puderbach Michael U , Kauczor Hans-Ulrich , Heussel Claus P , Heussel Gudula , Wielpütz Mark O 
Published: July 2022

Background Recent studies support magnetic resonance angiography (MRA) as a diagnostic tool for pulmonary arterial disease. Purpose To determine MRA image quality and reproducibility, and the dependence of MRA image quality and reproducibility on disease severity in patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Material and Methods Twenty patients with COPD (mean age 66.5 ± 8.9 years; FEV1% = 42.0 ± 13.3%) and 15 with CF (mean age 29.3 ± 9.3 years; FEV1% = 66.6 ± 15.8%) underwent morpho-functional chest magnetic resonance imaging (MRI) including time-resolved MRA twice one month apart (MRI1, MRI2), and COPD patients underwent non-contrast computed tomography (CT). Image quality was assessed visually using standardized subjective 5-point scales. Contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR) were measured by regions of interest. Disease severity was determined by spirometry, a well-evaluated chest MRI score, and by computational CT emphysema index (EI) for COPD. Results Subjective image quality was diagnostic for all MRA at MRI1 and MRI2 (mean score = 4.7 ± 0.6). CNR and SNR were 4 43.8 ± 8.7 and 50.5 ± 8.7, respectively. Neither image quality score nor CNR or SNR correlated with FEV1% or chest MRI score for COPD and CF (r = 0.239–0.248). CNR and SNR did not change from MRI1 to MRI2 ( P = 0.434–0.995). Further, insignificant differences in CNR and SNR between MRA at MRI1 and MRI2 did not correlate with FEV1% nor chest MRI score in COPD and CF (r = −0.238–0.183), nor with EI in COPD (r = 0.100–0.111). Conclusion MRA achieved diagnostic quality in COPD and CF patients and was highly reproducible irrespective of disease severity. This supports MRA as a robust alternative to CT in patients with underlying muco-obstructive lung disease.
Altered Intestinal Permeability Biomarkers in Schizophrenia: A Possible Link with Subclinical Inflammation
Authors: Gokulakrishnan Kuppan , Nikhil Joyappa , VS Sreeraj , Holla Bharath , Thirumoorthy Chinnasamy , Sandhya Narasimhan , Nichenametla Sonika , Pathak Harsh , Shivakumar Venkataram , Debnath Monojit , Venkatasubramanian Ganesan , Varambally Shivarama 
Published: July 2022

Background and Purpose Emerging studies have shown that gut-derived endotoxins might play a role in intestinal and systemic inflammation. Although the significance of intestinal permeability in modulating the pathogenesis of Schizophrenia (SCZ) is recognized, not much data on the specific role of intestinal permeability biomarkers, viz., zonulin, lipopolysaccharide-binding protein (LBP), and intestinal alkaline phosphatase (IAP) in SCZ is available. Therefore, we measured the plasma levels of zonulin, LBP, and IAP and its correlation with neutrophil-to-lymphocyte ratio (NLR); a marker of systemic inflammation in patients with SCZ. Methods We recruited 60 individuals, patients with SCZ ( n = 40) and healthy controls ( n = 20), from a large tertiary neuropsychiatry center. Plasma levels of zonulin, IAP, and LBP were quantified by enzyme-linked immunosorbent assay. Results Plasma levels of both LBP and zonulin were significantly increased ( P <0.05), whereas the IAP levels ( P <0.05) were significantly decreased in patients with SCZ compared to healthy controls. Pearson correlation analysis revealed that zonulin and LBP had a significant positive correlation with NLR, and IAP negatively correlated with NLR. Individuals with SCZ had higher independent odds of zonulin [odds ratio (OR): 10.32, 95% CI: 1.85–57.12], LBP [OR: 1.039, 95% CI: 1.02–1.07], and IAP [OR: 0.643, 95% CI: 0.471–0.879], even after adjusting for potential confounders. Conclusion Our study demonstrates an association of zonulin, LBP, and IAP in Asian Indian SCZ patients and correlates with NLR. Our results indicate that low-grade inflammation induced by metabolic endotoxemia might be implicated in the pathoetiology of SCZ.
Sagittal Growth Restriction of the Midface Following Isolated Cleft Lip Repair: A Systematic Review and Meta-Analysis
Authors: Celie Karel-Bart , Wlodarczyk Jordan , Naidu Priyanka , Tapia Maria Fernanda , Nagengast Eric , Yao Caroline , Magee William 
Published: July 2022

Midface hypoplasia (MFH) is a long-term sequela of cleft lip and palate repair, and is poorly understood. No study has examined the aggregate data on sagittal growth restriction of the midface following repair of the lip, but not palate, in these patients. A systematic review of 3780 articles was performed. Twenty-four studies met inclusion criteria and 11 reported cephalometric measurements amenable to meta-analysis. Patients with Veau class I-III palatal clefts were included so long as they had undergone only lip repair. Groups were compared against both noncleft and unrepaired controls. Cephalometrics were reported for 326 patients (31.3% female). Noncleft controls had an average SNA angle of 81.25° ± 3.12°. The only patients demonstrating hypoplastic SNA angles were those with unilateral CLP with isolated lip repair (77.4° ± 4.22°). Patients with repaired CL had SNA angles similar to noncleft controls (81.4° ± 4.02°). Patients with unrepaired CLP and CL tended toward more protruding maxillae, with SNA angles of 83.3° ± 4.04° and 87.9° ± 3.11°, respectively. Notably, when comparing SNA angles between groups, patients with CLP with isolated lip repair had significantly more hypoplastic angles compared to those with repaired CL ( P < .0001). Patients with CLP with isolated lip repair were also more hypoplastic than noncleft controls ( P < .0001). In contrast, there was no significant difference between the SNA of patients with repaired CL and controls ( P = .648). We found that cleft lip repair only appeared to contribute to MFH in the setting of concurrent cleft palate pathology, suggesting that scarring from lip repair itself is unlikely to be the predominant driver of MFH development. However, studies generally suffered from inadequate reporting of timing, technique, follow-up time, and cleft severity.
Early onset, delayed diagnosis and laterality of breast carcinoma: Evidence from a tertiary care hospital
Authors: Sume Bickes Wube , Assefa Wubshet , Merkeb Alamneh Yoseph 
Published: July 2022

Objectives: To assess age at onset, delayed diagnosis and laterality of breast carcinoma among women at Debre Markos Comprehensive Specialized Hospital, North West Ethiopia. Methods: Hospital-based descriptive study was conducted on 120 breast carcinoma cases at pathology department of Debre Markos Comprehensive Specialized Hospital, from October 2019 to December 2021. The women aware of symptoms until first medical consultation time was asked. The height and weight of the women were measured using the height and weight scale. The attending physician examined both breasts and regional lymph nodes. Pathological features of breast carcinomas were recorded when biopsy results arrived at the pathology department. Data were entered in Epi data version 3.1. Then, it was exported to SPSS version 25.0 statistical software for analysis. Results: Mean age of women was 39.9 ± 11.6 years, and median age was 38 years. Most women, 87 (72.5%) were aged less than 46 years. One hundred three (85.8%) women had complained breast lump pain for greater than 3 months before diagnosis. About 61 (50.8%) women had left breast carcinomas; 44 (36.7%) had right breast carcinomas and 15 (12.5%) had bilateral breast carcinomas. Of total, 53 (44.2%) cases were invasive ductal carcinomas; 41 (34.2%) had ductal carcinoma in situ; 14 (11.7%) were invasive lobular carcinomas; 8 (6.7%) were lobular carcinoma in situ and only 4 (3.3%) cases were mixed carcinomas. Conclusion: In this study, about two-third of the cases had early onset breast carcinoma. Most of the cases had delayed diagnosis of breast carcinoma. More than half of the cases had left breast carcinoma.
Technology-integrated Pedagogy, Learning Outcomes and Retention: Can Public–Private Partnerships Play a Role in Primary Education in India?
Authors: Bandyopadhyay Simanti , Sharma Aishna 
Published: July 2022

We undertake a case study on the SHIKSHA initiative in Uttar Pradesh in Northern India to understand how impactful the technology-integrated pedagogy through public–private partnerships (PPP) in education has been on the learning outcomes of students. A content analysis to understand the processes adopted by the SHIKSHA initiative is attempted. The digitized curriculum developed is found to be contextualized in accordance with the background of students, which can be aligned with constructivist learning theory. We also attempt a quantitative analysis to estimate the impact of these pedagogical practices on learning outcomes. The analysis finds that the average scores of schools with SHIKSHA interventions are higher by 58 percentage points. Also, under SHIKSHA, a 15-day period was given to the students for revision of the courses with the active participation of the teachers. The average scores after these revisions record an improvement as compared to the average scores before revisions. The paper suggests that the digitization of content by the government or through PPPs can help boost effective learning. JEL Classifications: C120, H520, I200, I210, I220, I280
Polarized Citizen Preferences for the Ethical Allocation of Scarce Medical Resources in 20 Countries
Authors: Awad Edmond , Bago Bence , Bonnefon Jean-François , Christakis Nicholas A. , Rahwan Iyad , Shariff Azim 
Published: July 2022

Objective. When medical resources are scarce, clinicians must make difficult triage decisions. When these decisions affect public trust and morale, as was the case during the COVID-19 pandemic, experts will benefit from knowing which triage metrics have citizen support. Design. We conducted an online survey in 20 countries, comparing support for 5 common metrics (prognosis, age, quality of life, past and future contribution as a health care worker) to a benchmark consisting of support for 2 no-triage mechanisms (first-come-first-served and random allocation). Results. We surveyed nationally representative samples of 1000 citizens in each of Brazil, France, Japan, and the United States and also self-selected samples from 20 countries (total N = 7599) obtained through a citizen science website (the Moral Machine). We computed the support for each metric by comparing its usability to the usability of the 2 no-triage mechanisms. We further analyzed the polarizing nature of each metric by considering its usability among participants who had a preference for no triage. In all countries, preferences were polarized, with the 2 largest groups preferring either no triage or extensive triage using all metrics. Prognosis was the least controversial metric. There was little support for giving priority to healthcare workers. Conclusions. It will be difficult to define triage guidelines that elicit public trust and approval. Given the importance of prognosis in triage protocols, it is reassuring that it is the least controversial metric. Experts will need to prepare strong arguments for other metrics if they wish to preserve public trust and morale during health crises. Highlights We collected citizen preferences regarding triage decisions about scarce medical resources from 20 countries. We find that citizen preferences are universally polarized. Citizens either prefer no triage (random allocation or first-come-first served) or extensive triage using all common triage metrics, with “prognosis” being the least controversial. Experts will need to prepare strong arguments to preserve or elicit public trust in triage decisions.
T-cell exhaustion induced by continuous bispecific molecule exposure is ameliorated by treatment-free intervals
Authors: Philipp Nora , Kazerani Maryam , Nicholls Alyssa , Vick Binje , Wulf Jan , Straub Tobias , Scheurer Michaela , Muth Amelie , Hänel Gerulf , Nixdorf Daniel , Sponheimer Monika , Ohlmeyer Malte , Lacher Sonja M. , Brauchle Bettina , Marcinek Anetta , Rohrbacher Lisa , Leutbecher Alexandra , Rejeski Kai , Weigert Oliver , von Bergwelt-Baildon Michael , Theurich Sebastian , Kischel Roman , Jeremias Irmela , Bücklein Veit , Subklewe Marion 
Published: July 2022

Abstract
T-cell–recruiting bispecific molecule therapy has yielded promising results in patients with hematologic malignancies; however, resistance and subsequent relapse remains a major challenge. T-cell exhaustion induced by persistent antigen stimulation or tonic receptor signaling has been reported to compromise outcomes of T-cell–based immunotherapies. The impact of continuous exposure to bispecifics on T-cell function, however, remains poorly understood. In relapsed/refractory B-cell precursor acute lymphoblastic leukemia patients, 28-day continuous infusion with the CD19xCD3 bispecific molecule blinatumomab led to declining T-cell function. In an in vitro model system, mimicking 28-day continuous infusion with the half-life–extended CD19xCD3 bispecific AMG 562, we identified hallmark features of exhaustion arising over time. Continuous AMG 562 exposure induced progressive loss of T-cell function (day 7 vs day 28 mean specific lysis: 88.4% vs 8.6%; n = 6; P = .0003). Treatment-free intervals (TFIs), achieved by AMG 562 withdrawal, were identified as a powerful strategy for counteracting exhaustion. TFIs induced strong functional reinvigoration of T cells (continuous vs TFI-specific lysis on day 14: 34.9% vs 93.4%; n = 6; P &lt; .0001) and transcriptional reprogramming. Furthermore, use of a TFI led to improved T-cell expansion and tumor control in vivo. Our data demonstrate the relevance of T-cell exhaustion in bispecific antibody therapy and highlight that T cells can be functionally and transcriptionally rejuvenated with TFIs. In view of the growing number of bispecific molecules being evaluated in clinical trials, our findings emphasize the need to consider and evaluate TFIs in application schedules to improve clinical outcomes.