bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase I Dose-Escalation Trial of MIW815 (ADU-S100), an Intratumoral STING Agonist, in Patients with Advanced/Metastatic Solid Tumors or Lymphomas
Authors: Meric-Bernstam Funda , Sweis Randy F. , Hodi F. Stephen , Messersmith Wells A. , Andtbacka Robert H.I. , Ingham Matthew , Lewis Nancy , Chen Xinhui , Pelletier Marc , Chen Xueying , Wu Jincheng , Dubensky Thomas W. , McWhirter Sarah M. , Müller Thomas , Nair Nitya , Luke Jason J.
Published: October 2021

Purpose:

This phase I study assessed the safety, pharmacokinetics (PKs), and efficacy of MIW815 (ADU-S100), a novel synthetic cyclic dinucleotide that activates the stimulator of IFN genes (STING) pathway, in patients with advanced/metastatic cancers.

Patients and Methods:

Patients (n = 47) received weekly i.t. injections of MIW815, 50 to 6,400 μg, on a 3-weeks-on/1-week-off schedule.

Results:

A maximum tolerated dose was not reached. Most common treatment-related adverse events were pyrexia (17%), chills, and injection-site pain (each 15%). MIW815 was rapidly absorbed from the injection site with dose-proportional PK, a rapid terminal plasma half-life (approximately 24 minutes), and high interindividual variability. One patient had a partial response (PR; Merkel cell carcinoma); two patients had unconfirmed PR (parotid cancer, myxofibrosarcoma). Lesion size was stable or decreased in 94% of evaluable, injected lesions. RNA expression and immune infiltration assessments in paired tumor biopsies did not reveal significant on-treatment changes. However, increases in inflammatory cytokines and peripheral blood T-cell clonal expansion suggested systemic immune activation.

Conclusions:

MIW815 was well tolerated in patients with advanced/metastatic cancers. Clinical activity of single-agent MIW815 was limited in this first-in-human study; however, evidence of systemic immune activation was seen.
DNMT3A Harboring Leukemia-Associated Mutations Directs Sensitivity to DNA Damage at Replication Forks
Authors: Venugopal Kartika , Feng Yang , Nowialis Pawel , Xu Huanzhou , Shabashvili Daniil E. , Berntsen Cassandra M. , Kaur Prabhjot , Krajcik Kathryn I. , Taragjini Christina , Zaroogian Zachary , Casellas Román Heidi L. , Posada Luisa M. , Gunaratne Chamara , Li Jianping , Dupéré-Richer Daphné , Bennett Richard L. , Pondugula Santhi , Riva Alberto , Cogle Christopher R. , Opavsky Rene , Law Brian K. , Bhaduri-McIntosh Sumita , Kubicek Stefan , Staber Philipp B. , Licht Jonathan D. , Bird Jonathan E. , Guryanova Olga A.
Published: October 2021

Purpose:

In acute myeloid leukemia (AML), recurrent DNA methyltransferase 3A (DNMT3A) mutations are associated with chemoresistance and poor prognosis, especially in advanced-age patients. Gene-expression studies in DNMT3A-mutated cells identified signatures implicated in deregulated DNA damage response and replication fork integrity, suggesting sensitivity to replication stress. Here, we tested whether pharmacologically induced replication fork stalling, such as with cytarabine, creates a therapeutic vulnerability in cells with DNMT3A(R882) mutations.

Experimental Design:

Leukemia cell lines, genetic mouse models, and isogenic cells with and without DNMT3A(mut) were used to evaluate sensitivity to nucleoside analogues such as cytarabine in vitro and in vivo, followed by analysis of DNA damage and signaling, replication restart, and cell-cycle progression on treatment and after drug removal. Transcriptome profiling identified pathways deregulated by DNMT3A(mut) expression.

Results:

We found increased sensitivity to pharmacologically induced replication stress in cells expressing DNMT3A(R882)-mutant, with persistent intra–S-phase checkpoint activation, impaired PARP1 recruitment, and elevated DNA damage, which was incompletely resolved after drug removal and carried through mitosis. Pulse-chase double-labeling experiments with EdU and BrdU after cytarabine washout demonstrated a higher rate of fork collapse in DNMT3A(mut)-expressing cells. RNA-seq studies supported deregulated cell-cycle progression and p53 activation, along with splicing, ribosome biogenesis, and metabolism.

Conclusions:

Together, our studies show that DNMT3A mutations underlie a defect in recovery from replication fork arrest with subsequent accumulation of unresolved DNA damage, which may have therapeutic tractability. These results demonstrate that, in addition to its role in epigenetic control, DNMT3A contributes to preserving genome integrity during replication stress.

See related commentary by Viny, p. 573
Dexmedetomidine Attenuates Hypoxia/Reoxygenation Injury of H9C2 Myocardial Cells by Upregulating miR-146a Expression via the MAPK Signal Pathway
Authors: Chu Yi , Teng Jiwei , Feng Pin , Liu Hui , Wang Fangfang , Wang Haiyan
Published: October 2021

Introduction and Objective: Dexmedetomidine (Dex) and a number of miRNAs contribute to ischemia/reperfusion injury. We aimed to explore the role of Dex and miR-146a on myocardial cells injured by hypoxia/reoxygenation (H/R). Method: H9C2 cells were injured by H/R. Cell viability was tested using the cell counting kit-8. Lactate dehydrogenase (LDH) activity, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) levels were determined using commercial kits. Flow cytometry was performed to determine apoptosis rate and reactive oxygen species (ROS) level. Protein and mRNA levels were assessed using Western blot and qPCR. Results: miR-146a expression and cell viability of H9C2 cells were downregulated under the circumstance of H/R injury. The tendency could be reversed by Dex, which could also upregulate SOD activity and decrease apoptosis, LDH activity, MDA, 78-kDa glucose-regulated protein (GRP78), and C/EBP homologous protein (CHOP) levels of H9C2 cells. GRP78, CHOP levels, and cell viability were negatively modulated by miR-146a. Dex elevated cell viability, catalase, MnSOD, and NAD(P)H dehydrogenase (NQO1) levels but suppressed apoptosis rate, GRP78, and CHOP levels by increasing miR-146a expression and downregulating ROS, phosphorylation of p38, and extracellular signal-regulated kinases 1/2 levels. By using SB203580 (SB), the p38 mitogen-activated protein kinase (MAPK) inhibitor, Dex or the inhibition of miR-146 upregulated cell viability but downregulated GRP78 and CHOP levels. Conclusion: Dex might regulate miR-146a expression, which could further modulate the endoplasmic reticulum stress and oxidative stress and eventually affect the cell viability and apoptosis of myocardial cells injured by H/R via the MAPK signal pathway.
The Influence of Hyperoxygenation on Fetal Brain Vascularity Measured Using 3D Power Doppler Ultrasound and the Index “Fractional Moving Blood Volume”
Authors: Issa Evitta , Stevenson Gordon Niall , Gomes De Melo Tavares Ferreira Ana Elizabeth , Chang Melissa Han Yiin , Alphonse Jennifer , Welsh Alec William
Published: October 2021

Introduction: Maternal hyperoxygenation effects on fetal cerebral hemodynamics are largely unknown. This study aimed to determine efficacy and reliability of a validated power Doppler ultrasound (US) index, fractional moving blood volume (FMBV), at measuring fetal cerebral vasculature changes during maternal hyperoxia. Methods: The fetal cerebral effects of 10 min of hyperoxygenation at 2 flow rates (52%/60% FiO2) were evaluated in women in their third trimester of pregnancy. 2D-US and 3D-US in a transverse plane were performed before, during, and following maternal hyperoxygenation with FMBV estimation performed offline. Results: Forty-five cases provided data for analysis. Mean intraobserver ICCs were 0.89 (3D-FMBV) and 0.84 (2D-FMBV). A significant difference in vascularity before and during and before and after 60% hyperoxia was observed (p < 0.05), whereas no significant differences were found at 52% hyperoxia (p > 0.05). Significant differences in vascularity were found between 2D-FMBV and 3D-FMBV (p < 0.01). Conclusion: Measurement of fetal cerebral vascularity by 3D-FMBV and 2D-FMBV was highly reproducible. The differing cerebral vascular changes seen with 60% but not 52% FiO2 suggest a possible “threshold effect” that may have influenced prior studies. Further studies are needed to assess cerebral effects of maternal hyperoxygenation on compromised fetuses.
Pyoderma Gangrenosum and Interleukin Inhibitors: A Semi-Systematic Review
Authors: Ben Abdallah Hakim , Fogh Karsten , Vestergaard Christian , Bech Rikke
Published: October 2021

Background: Pyoderma gangrenosum (PG) is a rare ulcerating skin disease associated with multiple comorbidities and increased mortality. In recent decades, newer biologics such as interleukin inhibitors have been used to treat PG; however, the literature is scarce, consisting predominantly of case reports and caseseries. The aim of our review was to evaluate the effectiveness and safety of interleukin inhibitors for the treatment of PG in adults. Summary: A literature search was conducted using search terms related to PG and interleukin inhibitors in databases such as PubMed, Embase, Scopus, Web of Science, and Cochrane Library. The study eligibility criteria included patients diagnosed with PG, over the age of 18, and treated with an interleukin inhibitor. Our study included 60 papers describing 81 patients fulfilling the eligibility criteria. The treatment with interleukin inhibitors resulted in 70% (95% CI 59–80%) response and 57% (95% CI 45–68%) complete response rates, and few (4%) mild adverse events, hence supporting the off-label use for the treatment of recalcitrant PG in adults. The response and complete response rates were 59% (17/29) and 38% (11/29) for anakinra, 64% (7/11) and 55% (6/11) for canakinumab, and 79% (27/34) and 71% (24/34) for ustekinumab, respectively. Limitations include publication bias that might have overestimated the efficacy as successful cases responding to treatment are more likely to be reported than nonresponding cases. Additionally, the heterogeneity of the treatment groups does not allow conclusions of superiority or inferiority of the different interleukin inhibitors to be drawn. Further studies are needed to investigate the efficacy of the different interleukin inhibitors and to investigate the importance of underlying disease for treatment response.
Association of Polycythemia with Outcomes of Acute Coronary Syndrome
Authors: Marcus Gil , Farkouh Michael E. , Minha Sa’ar , Fuchs Shmuel , Kalmanovich Eran , Beigel Roy , Iakobishvili Zaza , Klempfner Robert , Matezky Shlomo , Marcus Ronit
Published: October 2021

Background: Polycythemia has not been extensively studied for its impact on acute coronary syndrome (ACS) outcomes. A previous study reported only 30-day outcomes to be worse in these patients. Methods: Data from the ACS Israeli survey between 2000 and 2018 were utilized to compare between 3 groups of patients with ACS: anemic group (hemoglobin <12 g/dL for women and <12.5 g/dL for men), normal hemoglobin group, and polycythemic group (>16 g/dL and >16.5 g/dL, respectively). Measured outcomes included 30-day major adverse cardiac events (MACE comprising all-cause mortality, recurrent ACS, need for urgent revascularization, and stroke) and 1- and 5-year all-cause mortality. Results: Of 14,746 ACS patients, 10,752 (72.9%) had normal hemoglobin levels, 3,492 (23.7%) were anemic, and 502 (3.4%) were polycythemic. In comparison with normal and anemic patients, polycythemic patients were younger (55.9 ± 10.5 vs. 61.9 ± 12.4 and 71.1 ± 12.2 for anemic, respectively, p < 0.001 for both), more frequently men (93.8% vs. 81.3% and 63.1%, respectively, p < 0.001), and less likely diabetic or hypertensive. Upon adjustment to baseline characteristics, compared with normal hemoglobin, polycythemia was not independently associated with 30-day MACE or 1-year mortality, but it was independently associated with higher risk for 5-year mortality (HR 1.76, 95% CI: 1.19–2.59, p = 0.005). Similar results were observed after propensity score matching. Conclusions: Although younger and with fewer comorbidities, polycythemic ACS patients are at increased risk for long-term all-cause mortality. Further study of this association is warranted to understand the causes and possibly to improve the outcomes of these patients.
Hour-Specific Total Serum Bilirubin Percentiles for Infants Born at 29–35 Weeks’ Gestation
Authors: Jegathesan Thivia , Ray Joel G. , Bhutani Vinod K. , Keown-Stoneman Charles Donald George , Campbell Douglas M. , Shah Vibhuti , Berger Howard , Hayeems Robin Z. , Sgro Michael ,   for the NeoHBC
Published: October 2021

Introduction: As preterm infants are susceptible to hyperbilirubinemia, they require frequent close monitoring. Prior to initiation of phototherapy, hour-specific total serum bilirubin (TSB) percentile cut-points are lacking in these infants, which led to the current study. Methods: A multi-site retrospective cohort study of preterm infants born between January 2013 and June 2017 was completed at 3 NICUs in Ontario, Canada. A total of 2,549 infants born at 290/7–356/7 weeks’ gestation contributed 6,143 pre-treatment TSB levels. Hour-specific TSB percentiles were generated using quantile regression, further described by degree of prematurity, and among those who subsequently received phototherapy. Results: Among all infants, at birth, hour-specific pre-treatment, TSB percentiles were 36.1 µmol/L (95% confidence interval [CI]: 34.3–39.3) at the 40th, 52.3 µmol/L (49.4–55.1) at the 75th, and 79.5 µmol/L (72.1–89.6) at the 95th percentiles. The corresponding percentiles were 39.3 μmol/L (35.9–43.2), 55.4 μmol/L (52.1–60.2), and 87.1 μmol/L (CI 70.5–102.4) prior to initiating phototherapy and 24.4 μmol/L (20.4–28.8), 35.3 μmol/L (31.1–41.5), and 52.0 μmol/L (46.1–62.4) among those who did not receive phototherapy. Among infants born at 29–32 weeks, pre-treatment TSB percentiles were 53.9 µmol/L (49.4–61.0) and 95.5 µmol/L (77.5–105.0) at the 75th and 95th percentiles, with respective values of 48.7 µmol/L (43.0–52.3), and 74.1 µmol/L (64.8–83.2) for those born at 33–35 weeks’ gestation. Conclusion: Hour-specific TSB percentiles, derived from a novel nomogram, may inform how bilirubin is described in preterm newborns. Further research of pre-treatment TSB levels is required before clinical consideration.
Decreases in Brain Size and Encephalization in Anatomically Modern Humans
Authors: Stibel Jeff Morgan
Published: October 2021

Growth in human brain size and encephalization is well documented throughout much of prehistory and believed to be responsible for increasing cognitive faculties. Over the past 50,000 years, however, both body size and brain mass have decreased but little is known about the scaling relationship between the two. Here, changes to the human brain are examined using matched body remains to determine encephalization levels across an evolutionary timespan. The results find decreases to encephalization levels in modern humans as compared to earlier Holocene H. sapiens and Late Pleistocene anatomically modern Homo. When controlled for lean body mass, encephalization changes are isometric, suggesting that much of the declines in encephalization are driven by recent increases in obesity. A meta-review of genome-wide association studies finds some evidence for selective pressures acting on human cognitive ability, which may be an evolutionary consequence of the more than 5% loss in brain mass over the past 50,000 years.
Macroinvertebrates responses based on chemical and physical variables in urban streams
Authors: Barrilli Germano Henrique Costa , Negreiros Natalia Felix , Rocha Odete , Verani José Roberto
Published: October 2021

The Land uses and occupations around small watersheds generate negative impacts such as deterioration of water quality, environmental simplification, reduced availability of habitats for species, and loss of biodiversity. Benthic macroinvertebrates are an important aquatic community and are widely used in environmental monitoring actions in aquatic ecosystems, including urban streams, which are still little studied in Brazil. In our study, an urban headwater basin (Monjolinho River Basin) was studied on the benthic community structure, together with the physical and chemical variables of the water, as an environmental monitoring tool calculated by RHDEP, TSI, BMWP indexes and abundance-biomass curves. The results showed a gradient of environmental quality, where the best environments are a consequence of preserving the vegetation cover. These environments (Espraiado and Canchim) present groups sensitive to environmental degradation (Ephemeroptera, Plecoptera and Trichoptera), greater diversity and a better structure in the respective benthic macroinvertebrate assemblages. Among the streams sampled, one is very clean, four are moderately polluted, and one is severely polluted. Thus, considering that these streams’ waters are essential for public supply, actions to clean up and recover degraded environments are urgent and a priority.
Stapafurdius, a new genus of Bulimulidae (Mollusca, Eupulmonata) from Bahia, Brazil, with two new species
Authors: Simone Luiz Ricardo L.
Published: October 2021

The new genus Stapafurdius gen. nov. is introduced collected from Bahia, Brazil, including two new species: S. glaber sp. nov., the type species, occurs in Ibicoara; and S. costiferus sp. nov., from Andaraí regions. The new genus includes species of about 10 mm, elongated shell, reticulated protoconch, elongated peristome, and wide umbilicus. Both species differ mainly by the sculpture, as S. glaber sp. nov. is smooth, while S. costiferus sp. nov. has strong axial sculpture. urn:lsid:zoobank.org:pub:C851695E-6BF1-4418-8D8A-8BC7D10CC2FE.
An unusual cryptogeobiid from southeastern Brazil revisited (Opiliones, Laniatores, Gonyleptoidea)
Authors: Kury Adriano Brilhante , Caramori Laura Regina
Published: October 2021

The monotypic genus Bunostigma Mello-Leitão, 1935 is herein revisited. A detailed redescription of its type-species, Bunostigma singulare Mello-Leitão, 1935 from Rio de Janeiro state, eastern Brazil, is herein presented, providing in depth knowledge of this genus. Bunostigma is most closely related to Cryptogeobius Mello-Leitão, 1935, and as this genus, it has a stout complex apophysis on male coxa IV, lacking, however, a second complex on the stigmatic area. Bunostigma has an oblique elongate malleus, similar to that of Zalanodius Mello-Leitão, 1936 (as opposed to a globular malleus in Cryptogeobius). Bunostigma singulare has short legs, with some sexual dimorphism on its stoutness, a dorsal scutum entirely unarmed and an ocularium with an accessory central mound, although unarmed.
Perfil do controller e suas escolhas estratégicas: uma análise sobre controllers brasileiros e portugueses
Authors: Ferreira Mônica Aparecida , Leal Edvalda Araújo , Ferreira Ana Maria Dias Simões da Costa , Ferreira Layne Vitória
Published: October 2021

O presente artigo tem como objetivo compreender como os valores e a base cognitiva propostos pela Teoria dos Altos Escalões são percebidos nas escolhas estratégicas de controllers que atuam em empresas do Brasil e de Portugal. Trata-se de um estudo descritivo com abordagem qualitativa. Os dados foram coletados entre os anos de 2018 a 2020 a partir de entrevistas realizadas com controllers e ex-controllers vinculados a empresas de diferentes segmentos dos dois países. No total, foram realizadas vinte e três entrevistas, tendo sido os dados analisados por meio da análise de conteúdo. Os resultados revelaram que a experiência profissional prévia e a formação acadêmica dos profissionais, assim como o perfil do indivíduo, a estrutura hierárquica, a cultura organizacional e o nível de autonomia que é dado aos controllers, interferem em suas escolhas estratégicas em ambos os países. Coletivismo, racionalidade, dever e inovação foram os valores mais destacados pelos entrevistados como sendo essenciais para o cargo de controller.
Elevated Aortic Pulse Wave Velocity Relates to Longitudinal Gray and White Matter Changes
Authors: Bown Corey W. , Khan Omair A. , Moore Elizabeth E. , Liu Dandan , Pechman Kimberly R. , Cambronero Francis E. , Terry James G. , Nair Sangeeta , Davis L. Taylor , Gifford Katherine A. , Landman Bennett A. , Hohman Timothy J. , Carr John Jeffrey , Jefferson Angela L.
Published: October 2021

Objective:

To determine whether baseline aortic stiffness, measured by aortic pulse wave velocity (PWV), relates to longitudinal cerebral gray or white matter changes among older adults. Baseline cardiac magnetic resonance imaging will be used to assess aortic PWV while brain magnetic resonance imaging will be used to assess gray matter and white matter hyperintensity (WMH) volumes at baseline, 18 months, 3 years, 5 years, and 7 years.

Approach and Results:

Aortic PWV (m/s) was quantified from cardiac magnetic resonance. Multimodal 3T brain magnetic resonance imaging included
T

1

-weighted imaging for quantifying gray matter volumes and
T

2

-weighted fluid-attenuated inversion recovery imaging for quantifying WMHs. Mixed-effects regression models related baseline aortic PWV to longitudinal gray matter volumes (total, frontal, parietal, temporal, occipital, hippocampal, and inferior lateral ventricle) and WMH volumes (total, frontal, parietal, temporal, and occipital) adjusting for age, sex, race/ethnicity, education, cognitive diagnosis, Framingham stroke risk profile,
APOE
(apolipoprotein E)-ε4 carrier status, and intracranial volume. Two hundred seventy-eight participants (73±7 years, 58% male, 87% self-identified as non-Hispanic White, 159 with normal cognition, and 119 with mild cognitive impairment) from the Vanderbilt Memory & Aging Project (n=335) were followed on average for 4.9±1.6 years with PWV measurements occurring from September 2012 to November 2014 and longitudinal brain magnetic resonance imaging measurements occurring from September 2012 to June 2021. Higher baseline aortic PWV was related to greater decrease in hippocampal (β=−3.6 [mm
3
/y]/[m/s]; [95% CI, −7.2 to −0.02]
P
=0.049) and occipital lobe (β=−34.2 [mm
3
/y]/[m/s]; [95% CI, −67.8 to −0.55]
P
=0.046) gray matter volume over time. Higher baseline aortic PWV was related to greater increase in WMH volume over time in the temporal lobe (β=17.0 [mm
3
/y]/[m/s]; [95% CI, 7.2–26.9]
P
<0.001). All associations may be driven by outliers.

Conclusions:

In older adults, higher baseline aortic PWV related to greater decrease in gray matter volume and greater increase in WMHs over time. Because of unmet cerebral metabolic demands and microvascular remodeling, arterial stiffening may preferentially affect certain highly active brain regions like the temporal lobes. These same regions are affected early in the course of Alzheimer disease.
Perinatal Administration of C-Phycocyanin Protects Against Atherosclerosis in apoE-Deficient Mice by Modulating Cholesterol and Trimethylamine-N-Oxide Metabolisms
Authors: Coué Marine , Croyal Mikael , Habib Marina , Castellano Blandine , Aguesse Audrey , Grit Isabelle , Gourdel Mathilde , Billard Hélène , Lépine Olivier , Michel Catherine , Ouguerram Khadija
Published: October 2021

Objective:

Gestational hypercholesterolemia concomitantly with a highly oxidative environment is associated with higher atherosclerosis in human and animal offspring. This work aimed to determine whether perinatal administration of a C-phycocyanin concentrate, a powerful antioxidant, can protect against atherosclerosis development in genetically hypercholesterolemic mice in adult life.

Approach and Results:

C-Phycocyanin was administered during gestation solely or gestation and lactation to apolipoprotein E-deficient mice. Male and female offspring were studied until 25 weeks old. Progenies born to supplemented mothers displayed significantly less atherosclerotic root lesions than control group in all groups excepted in male supplemented during gestation and lactation. Female born to supplemented mothers had a greater gallbladder total bile acid pool, lower secondary hydrophobic bile acid levels such as lithocholic acid, associated with less plasma trimethylamine
N
-oxide at 16 weeks old compared with control mice. Regarding male born to C-Phycocyanin administrated mothers, they expressed a higher high-density lipoprotein cholesterol level, more soluble bile acids such as β-muricholic acids, and a decreased plasma trimethylamine at 16 weeks old. Liver reduced-to-oxidized glutathione ratio were increased and liver gene expression of superoxide dismutase and glutathione peroxidase were significantly decreased in male born to gestational supplemented mothers. No difference in the composition of cecal microbiota was found between groups, regardless of sex.

Conclusions:

Our findings suggest a protective effect of perinatal antioxidant administration on atherosclerosis development in apolipoprotein E-deficient mice involving sex-specific mechanisms.
Impact of High-Power Short-Duration Radiofrequency Ablation on Esophageal Temperature Dynamic
Authors: Yavin Hagai D. , Bubar Zachary P. , Higuchi Koji , Sroubek Jakub , Kanj Mohamed , Cantillon Daniel , Saliba Walid I. , Tarakji Khaldoun G. , Hussein Ayman A. , Wazni Oussama , Anter Elad
Published: October 2021

Background:

High-power short-duration (HP-SD) radiofrequency ablation (RFA) has been proposed as a method for producing rapid and effective lesions for pulmonary vein isolation. The underlying hypothesis assumes an increased resistive heating phase and decreased conductive heating phase, potentially reducing the risk for esophageal thermal injury. The objective of this study was to compare the esophageal temperature dynamic profile between HP-SD and moderate-power moderate-duration (MP-MD) RFA ablation strategies.

Methods:

In patients undergoing pulmonary vein isolation, RFA juxtaposed to the esophagus was delivered in an alternate sequence of HP-SD (50 W, 8–10 s) and MP-MD (25 W, 15–20 s) between adjacent applications (distance, ≤4 mm). Esophageal temperature was recorded using a multisensor probe (CIRCA S-CATH). Temperature data included magnitude of temperature rise, maximal temperature, time to maximal temperature, and time return to baseline. In swine, a similar experimental design compared the effect of HP-SD and MP-MD on patterns of esophageal injury.

Results:

In 20 patients (68.9±5.8 years old; 60% persistent atrial fibrillation), 55 paired HP-SD and MP-MD applications were analyzed. The esophageal temperature dynamic profile was similar between HP-SD and MP-MD ablation strategies. Specifically, the magnitude of temperature rise (2.1 °C [1.4–3] versus 2.0 °C [1.5–3];
P
=0.22), maximal temperature (38.4 °C [37.8–39.3] versus 38.5 °C [37.9–39.4];
P
=0.17), time to maximal temperature (24.9±7.5 versus 26.3±6.8 s;
P
=0.1), and time of temperature to return to baseline (110±23.2 versus 111±25.1 s;
P
=0.86) were similar between HP-SD and MP-MD ablation strategies. In 6 swine, esophageal injury was qualitatively similar between HP-SD and MP-MD strategies.

Conclusions:

Esophageal temperature dynamics are similar between HP-SD and MP-MD RFA strategies and result in comparable esophageal tissue injury. Therefore, when using a HP-SD RFA strategy, the shorter application duration should not prompt shorter intervals between applications.
Differences Between Patients With Intermittent Claudication and Critical Limb Ischemia Undergoing Endovascular Intervention: Insights From the Excellence in Peripheral Artery Disease Registry
Authors: Patel Kunal , Liu Yulun , Etaee Farshid , Patel Chirag , Monteleone Peter , Patel Mitul , Amer Alaiti Mohamad , Metzger Christopher , Banerjee Avantika , Minniefield Nicole , Tejani Ishita , Brilakis Emmanouil S. , Shishehbor Mehdi H. , Banerjee Subhash
Published: October 2021

Background:

There are limited data on differences in angiographic distribution of peripheral artery disease and endovascular revascularization strategies in patients presenting with intermittent claudication (IC) and critical limb ischemia (CLI). We aimed to compare anatomic features, treatment strategies, and clinical outcomes between patients with IC and CLI undergoing endovascular revascularization.

Methods:

We examined 3326 patients enrolled in the Excellence in Peripheral Artery Disease registry from 2006 to 2019 who were referred for endovascular intervention for IC (n=1983) or CLI (n=1343). The primary outcome was 1-year major adverse limb events, which included death, repeat target limb revascularization, or target limb amputation.

Results:

Patients with CLI were older and more likely to have diabetes and chronic kidney disease and less likely to receive optimal medical therapy compared with IC. Patients with IC had higher femoropopliteal artery interventions (IC 87% versus CLI 65%;
P
<0.001), while below the knee interventions were more frequent in CLI (CLI 47% versus IC 12%;
P
<0.001). Patients with CLI were more likely to have multilevel peripheral artery disease (CLI 32% versus IC 15%,
P
<0.001). Patients with IC were predominantly revascularized with stents (IC 48% versus CLI 37%;
P
<0.001) while balloon angioplasty was more frequent in CLI (CLI 37% versus IC 25%;
P
<0.001). All-cause mortality was higher in patients with CLI (CLI 4% versus IC 2%;
P
=0.014). Major adverse limb event rates for patients with IC and CLI were 16% and 26%, respectively (
P
<0.001) and remained higher in CLI after multivariable adjustment of baseline risk factors.

Conclusions:

Patients with IC and CLI have significant anatomic, lesion, and treatment differences with significantly higher mortality and adverse limb outcomes in CLI.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01904851.

Graphic Abstract:

A
graphic abstract
is available for this article.
Which Road to Recovery?: Factors Influencing Postacute Stroke Discharge Destinations: A Delphi Study
Authors: Stein Joel , Rodstein Barry M. , Levine Steven R. , Cheung Ken , Sicklick Alyse , Silver Brian , Hedeman Robin , Egan Abigail , Borg-Jensen Pamela , Magdon-Ismail Zainab ,   on behalf of the Northeast Cerebrovascular Consortium Stroke Rehabilitation and Recovery Delphi Study Group
Published: October 2021

Background and Purpose:

The criteria for determining the level of postacute care for patients with stroke are variable and inconsistent. The purpose of this study was to identify key factors influencing the selection of postacute level of care for these patients.

Methods:

We used a collaborative 4-round Delphi process to achieve a refined list of factors influencing postacute level of care selection. Our Delphi panel of experts consisted of 32 panelists including physicians, physical therapists, occupational therapists, speech-language pathologists, nurses, stroke survivors, administrators, policy experts, and individuals associated with third-party insurance companies.

Results:

In round 1, 207 factors were proposed, with subsequent discussion resulting in consolidation into 15 factors for consideration. In round 2, 15 factors were ranked with consensus on 10 factors; in round 3,10 factors were ranked with consensus on 9 factors. In round 4, the final round, 9 factors were rated with Likert scores ranging from 5 (most important) to 1(not important). The percentage of panelists who provided a rating of 4 or above were as follows: likelihood to benefit from an active rehabilitation program (97%), need for clinicians with specialized rehabilitation skills (94%), need for active and ongoing medical management and monitoring (84%), ability to tolerate an active rehabilitation program (74%), need for caregiver training to return to the community (48%), family/caregiver support (39%), likelihood to return to community/home (39%), ability to return to physical home environment (32%), and premorbid dementia (16%).

Conclusions:

This study provides an expert, consensus-based set of key factors to be considered when determining where stroke patients are discharged for postacute care. These factors may be useful in developing a decision support tool for use in clinical settings.
וילך שם (Ezra 10:6): “Wandering About” as a Sign of Mourning
Authors: Shemesh Yael
Published: October 2021

In a fascinating article, Michael L. Barré noted the topos of “wandering about” as a symptom of depression and mourning in world literature in general, and in the literature of the ancient Near East and the Bible in particular. Building on his insights, this paper argues that the phrase “he went there” (וילך שם) from Ezra 10:6 builds another instance of the topos of “wandering about.” Thus, there is no need to emed MT to “he spent the night there” (וילן שם), as has often been suggested.
A Cathedral with Disconnected Chapels? Reassessing the Cognitive Capacities of Neanderthals in Light of Recent Archaeological Discoveries
Authors: Liu Cheng
Published: October 2021

The reconstruction of hominins’ cognitive evolution has always been a crucial but challenging task. Researchers from various disciplines have tried to approach this issue, among which British archaeologist Steven Mithen’s cathedral model is regarded as one of the earliest and most creative attempts. In this model, he proposed that the Neanderthal’s mind is like a cathedral with disconnected chapels. Specifically, Neanderthals possessed advanced social, natural history, technical, and even linguistic intelligence modules, but the first three modules are isolated from each other, meaning they cannot effectively use the knowledge from one domain to address the issue of another domain. This article challenges his reconstruction of Neanderthals’ cognitive capacities by presenting multiple forms of archaeological evidence bearing on various kinds of cross-domain thinking that has arisen over the past two decades.
Between Sanudo and Fedanzola: Ashtori Ha-Parḥi as Mediator
Authors: Schwartz Amichay
Published: October 2021

This essay will examine the close similarity between the treatises of a Franciscan monk named Giovanni di Fedanzola and a Jewish sage named Ashtori Ha-Parḥi in the fourteenth-century Holy Land. The absence of guides for Christian pilgrims after the final departure of the Crusaders in 1291 was filled inter alia by Jews, and some new traditions regarding toponyms and geographical identifications were adopted by Christians as a result. Fedanzola mostly relied on his predecessors Burchardus de Monte Sion and Marino Sanudo. However, I will demonstrate that there are some instances where Fedanzola accepts Jewish traditions regarding locations mentioned in the Old Testament, with Ashtori Ha-Parḥi as his source. I will also show that positing a relationship between the two can clarify some obscure passages in Ashtori’s treatise, Kaftor va-feraḥ.
Divine Incomprehensibility and Human Faith in John Chrysostom
Authors: Edwards Robert G.T.
Published: October 2021

Although often considered a moralist, John Chrysostom frequently discusses the incomprehensibility of God. This paper both contextualizes his teaching on divine incomprehensibility within a pro-Nicene tradition and demonstrates what is particular to his own theology. It puts forward two major arguments. First, Chrysostom expands upon a pro-Nicene discourse of divine incomprehensibility – as also seen in Basil of Caesarea and Gregory of Nazianzus – to include not only the incomprehensibility of God’s essence but also the incomprehensibility of God’s economies. Second, Chrysostom’s apparently simplistic biblicism and doctrine of faith are in fact theological corollaries of this doctrine of divine incomprehensibility. In these ways, Chrysostom’s moral teaching is seen to have a robust theological basis.
Why Did Jesus Surrender to the Cross?
Authors: Mowbray John
Published: October 2021

Evidence from secular sources shows that the Romans did not attempt to crucify all in the empire who rose against them; rather, they crucified leaders as a warning to others, but often let followers go. Jesus believed or hoped that if he surrendered to the cross, though the Romans would crucify him as leader, they would let his followers go. He surrendered himself accordingly, to save his followers from suffering a similar fate. As a historical fact, this was successful, and his followers were preserved to become the beginnings of the church.
Gender and Transnational Dynamics in Immigrant Entrepreneurship
Authors: You (游天龙) Tianlong , Zhou (周敏) Min
Published: October 2021

Immigrant enterprises, especially those in the service sector of the urban economy, are largely gendered and seemingly localized. However, the intersection of gender and transnationalism is often overlooked in the research literature. To fill this gap, we draw on the literature of mixed embeddedness and transnationalism to advance an analytical framework of simultaneous embeddedness to explain the gendered pattern of immigrant entrepreneurship. We do so by taking an in-depth look at a female-dominant industry – Chinese-owned nail salons in New York City. Using data collected from face-to-face interviews and on-site observations in New York City, as well as archival records and media reports about labor-market dynamics in both the United States and China, we find that the development of Chinese-owned nail salons is shaped by contextual factors in both home and host countries beyond socioeconomic characteristics of individual entrepreneurs. Home-country factors in China include labor-force demographics, access to economic opportunities, and the gap between education and career aspiration among young women. These home-country factors are intertwined with changes in US immigration policy, local labor-market reception, and gender discrimination, which function to exacerbate the problem of labor shortage for Chinese-owned nail salons in New York City. We discuss the significance of simultaneous embeddedness and gender in understanding contemporary immigrant entrepreneurship.
Past Facts and the Nature of History
Authors: Currie Adrian , Swaim Daniel
Published: October 2021

We defend a realist account of history: past facts are discoveries not creations. We show how ‘moderate’ realists, who admit the critical role of perspective, while insisting on history’s metaphysical independence from historians, can accommodate Paul Roth’s arguments in favor of irrealism. Moreover, our position is consistent with a dynamic past: as history unfurls past events gain new properties. Realism is necessary, we argue, to capture substantive disputes within history. It also grounds history’s reflexivity: the point of the continual re-examination of history (and history’s history!) turns in part on there being mind-independent past facts to be had.
The Extended-Expert-As-Teacher (EEAT) Model
Authors: Blado Joseph E.
Published: October 2021

Recently, social epistemologists have sought to establish what the governing epistemic relationship should be between novices and experts. In this article, the author argues for, and expands upon, Helen De Cruz’s expert-as-teacher model. For although this model is vulnerable to significant challenges, the author proposes that a specifically extended version can sufficiently overcome these challenges (call this the “extended-expert-as-teacher” model, or the “EEAT” model). First, the author shows the respective weaknesses of three influential models in the literature. Then, he argues the expert-as-teacher model can overcome its weaknesses by adding what he calls the “Authority Clause”, “Advisor Clause”, and “Ex Post Facto Clause” of the EEAT model. After developing a robust account of these clauses, the author entertains three major objections. First, he responds to the charge that the EEAT model is little better than the expert-as-authority model. Second, he responds to a double-counting objection. Lastly, he responds to a pragmatic objection from complexity.
Non-uniformism and the Epistemology of Philosophically Interesting Modal Claims
Authors: Sjölin Wirling Ylwa
Published: October 2021

Philosophers often make exotic-sounding modal claims, such as: “A timeless world is impossible”, “The laws of physics could have been different from what they are”, “There could have been an additional phenomenal colour”. Otherwise popular empiricist modal epistemologies in the contemporary literature cannot account for whatever epistemic justification we might have for making such modal claims. Those who do not, as a result of this, endorse scepticism with respect to their epistemic status typically suggest that they can be justified but have yet to develop some distinct, workable theory of how. That is, they endorse a form of non-uniformism about the epistemology of modality, according to which claims about philosophically interesting modal matters need to be justified differently from e.g. everyday or scientific modal claims, but they fail to provide any more detail. This article aims to fill this gap by outlining how such a non-uniformist view could be spelled out and what story about philosophically interesting modal justification it could contain.
‘The Japanese Stand Today as Teachers of the Whole World’: American Food Reform and the Russo-Japanese War
Authors: Guth Christine M. E.
Published: October 2021

Japanese food first became the focus of serious attention in the United States during the Russo-Japanese War (1904–1905), when Japan’s victory over the Russian empire signaled that nation’s arrival as a new world power. This newfound interest had nothing to do with gastronomy. The conviction driving it was that diet and preventative health care in the Japanese military, which had been critical to its unexpected success, could serve as models for the United States. Military doctors, home economists, dietitians, businesses, vegetarians, and physical fitness fans joined this discourse, each with their own agendas. Many participants were women whose advocacy linked the supposed innate feminine propensity for nurturing and care giving with a shared faith in science to solve the problems facing the modern world. All believed Japan’s rice, vegetable, and fish-based diet contributed to the exceptional physical strength and stamina of the Japanese people because, unlike their own, “it was plain, rational, and easily digested, metabolized and assimilated.” More enthusiasm than knowledge in their claims, but this mattered little since the goal was not to popularize Japanese culinary culture, but to reform U.S. eating habits. This article examines the American discourse on Japanese food and health and how it shaped and reflected domestic political, social, and economic priorities in the 20th Century’s first decade.
Contact-Induced Complexification in the Gender System of Istro-Romanian
Authors: Loporcaro Michele , Gardani Francesco , Giudici Alberto
Published: October 2021

The paper provides the first description of the borrowing of Croatian collective numerals into Northern Istro-Romanian and explores the consequences of this borrowing for the morphosyntax of the recipient language. It argues that the collective numerals under examination, which are specified as nominative plural feminine in the Slavic model, took on a different structural specification in the Romance replica, in a way that led to a restructuring of the morphosyntactic system, introducing (sub)gender overdifferentiation on just two agreement targets and, thereby, a complexification in this area of grammar. The illustration of this change is placed against the background of the other contact-induced changes that grammatical gender has undergone in Istro-Romanian during the 20th century, which have led to the borrowing of two dedicated forms in distinct inflectional cells and the rise of two separate defective gender values, each the replica of one number value of the Slavic neuter.
Contrasting Romance and Turkish as Source Languages: Evidence from Borrowing Verbs in Modern Greek Dialects
Authors: Ralli Angela
Published: October 2021

In this paper, I deal with verb borrowing in a language-contact situation involving Greek as target and Romance and Turkish as source languages. More particularly, I discuss the reasons and techniques that make verbs of typologically and genetically different languages to be accommodated in a uniform way within the same linguistic system, and verbs of the same donor to be integrated in a different manner within the same recipient. I try to provide an explanation for the observed divergences and similarities by appealing to an interplay of linguistic and extra-linguistic factors. For the purposes of this study, evidence is drawn from both written and oral sources from five Greek dialectal varieties: Grekanico, Heptanesian, Pontic, Aivaliot and Cypriot.
An Egyptian Medical Officer and Qurʾān Commentator in Ottoman Syria
Authors: Daneshgar Majid
Published: October 2021

This article pays a particular attention to an Arab army physician and scholar from the mid-19th century who placed empirical science at the center of Islamic thought and situated it within Qurʾānic exegetical debates. He is the Egyptian Muḥammad ibn Aḥmad al-Iskandarānī, a medical officer who ended up working in Ottoman Syria, and whose works were copied and printed (in)directly by the Ottomans. Apart from the limited information contained in previous scholarly literature, which, on the basis of his first commentary alone, repeatedly presents this commentator as one of the first people to have produced a “scientific interpretation of the Qurʾān”, little is known about his personal and professional background and the production of his commentaries. This study also sheds light on exegetical and intellectual directions produced outside Egypt in the 19th century.
Protective effect of Isoliquiritigenin on skin ischemia-reperfusion injury in rats
Authors: Zhou Guifang , Li Anju , Guo Qiuling , Song Chuanmin , Zhang Youwen
Published: October 2021

Skin ischemia-reperfusion (I/R) injury is a serious condition that compromises skin flap surgery and leads to organ dysfunction. It arose due to restoration of blood supply after prolonged ischemia. The present study was conducted to explore the possible protective Isoliquiritigenin (ISL) on skin ischemia-reperfusion injury in rats. The ISL was administered to rats in the dose of 10 mg/kg, 20 mg/kg, and 30 mg/kg. The effect of ISL was quantified on the skin tissue of rats following the I/R injury on various indices of inflammation, oxidative stress, and apoptosis together with the effect on skin survival. ISL improves the survival of skin which is further confirmed by the histopathological analysis. It also causes a reduction of apoptosis as shown by TUNEL staining. The level of oxidative stress was found significantly reduced by restoring the MDA, SOD, and GSH levels near to normal. The level of inflammation was also decreased as suggested by reduced level of cytokines, such as TNF-α, IL-1β, and IL-6. The ISL also causes a significant reduction of COX-2 and iNOS in western blot analysis. Collectively, our study has shown a beneficial effect of ISL against skin I/R injury via multiple mechanisms of action, such as attenuation of oxidative stress, inflammation, and apoptosis.