bluuebunny/crossref_metadata_2025 huggingface dataset:
Computing as Oppression: Authoritarian Technology Poses a Worldwide Threat
Authors: Schuler Douglas
Published: October 2022

The advent and ubiquity of interconnected digital computer systems provides a cornucopia of opportunities for enabling oppression. While commercial (legitimate and criminal) enterprises use these for questionable purposes, big governmental systems, generally with industry cooperation, pose substantial threats to freedom and democracy and to collective problem-solving abilities (civic intelligence) worldwide. The government of China has established a startlingly pervasive network of surveillance, censorship, and incarceration for social control and is now expanding that system domestically while making the tools within that system available worldwide. While there are other perpetrators, including the United States, China's approach is further advanced and has fewer constraints than those found in more democratic states. The new evolving control/surveillance infrastructure based substantially on technological advances presents ethical and practical dilemmas for computer professionals and their associations. The preamble of the ACM Code of Ethics and Professional Conduct states that in order to act responsibly, computing professionals “should reflect upon the wider impacts of their work, consistently supporting the public good.” This commentary intends to point out the urgency of these issues, contribute to the wider discussion, and encourage social responsibility within the profession.
Multichannel magnetogastrogram: a clinical marker for pediatric chronic nausea
Authors: Somarajan Suseela , Muszynski Nicole D. , Olson Joseph D. , Russell Alexandra C. , Walker Lynn S. , Acra Sari A. , Bradshaw Leonard A.
Published: October 2022

Pediatric chronic nausea is a difficult-to-measure subjective complaint that requires objective diagnosis, clinical assessment, and individualized treatment plans. Our study demonstrates that multichannel MGG used in conjunction with custom HR-EGG detects key pathological signatures of functional nausea in children. This quantifiable measure may allow more personalized diagnosis and treatment in addition to minimizing the cost and potential radiation associated with current diagnostic approaches.
Consistency Improvement Method of Pairwise Matrix Based on Consistency Ratio Decreasing Rate and Attribute Weighting Method Considered Decision Makers’ Levels in Analytic Hierarchy Process: Application to Hip Joint Prosthesis Material Selection
Authors: Yang Won-Chol , Kang Hyon-Song , Ri Gyong-Su , Kim Jin-Sim
Published: October 2022

Analytic hierarchy process (AHP) is a well-known attribute weighting method in multiattribute decision-making. Its major requirement is to satisfy the consistency of pairwise matrix (PM). To solve this problem, we first propose a new consistency improvement method of PM based on consistency ratio (CR) decreasing rate. In this method, we calculate the CR decreasing rates of all the PMs reconstituted by replacing all elements of the PM with the lower and upper neighbouring 9-point scales and find the element with maximum CR decreasing rate, and then modify it to its lower or upper neighbouring scale. Second, we develop third-order approximate polynomial for random consistency index using least square method. It enables to determine the RI value according to the number of attributes without a numerical table. Third, we propose the final PM determining method and final attribute weighting method considered decision makers’ levels based on the CR values of the individual PMs in case several decision makers perform their own pairwise comparisons. We test the performances of the proposed and some previous consistency improvement methods with two numerical examples. The results demonstrate that the proposed method improves the consistency of PM better and faster with smaller amount of modification than that of the previous methods, while it modify the elements of the PM to 9-point scales, necessarily. We apply the proposed method to hip joint prosthesis material selection. The proposed methods may be widely used in practical applications of AHP.
Hepatic Encephalopathy in Cirrhotic Patients and Risk of Small Intestinal Bacterial Overgrowth: A Systematic Review and Meta‐Analysis
Authors: Feng Xin , Li Xiaoqing , Zhang Xin , Chen Weiqing , Tian Yin , Yang Qingqing , Yang Yingying , Pan Hui , Jiang Zheng
Published: October 2022

Background. Hepatic encephalopathy (HE) is a neurological and psychiatric syndrome. Recent evidence suggests that HE is not only a disease of the liver and brain but is also related to the gut. Small intestinal bacterial overgrowth (SIBO) is well known to be associated with cirrhosis, but the relationship between SIBO and HE is unclear. We conducted this comprehensive systematic review and meta‐analysis to determine the association between SIBO and HE in cirrhotic patients. Methods. We conducted a comprehensive literature search of all studies on the association of SIBO and HE in cirrhotic patients using the PubMed and Embase electronic databases. Studies were screened, and relevant data were extracted and analysed. We calculated the number of cases of SIBO in patients with HE and controls. We then compared the prevalence of SIBO between the two groups to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Funnel plots were constructed to identify potential publication bias. Results. Six studies with 414 participants (219 HE patients and 195 controls) met the inclusion criteria. The prevalence of SIBO in cirrhotic patients with HE was significantly higher than that in those without HE. The combined OR was 4.43 (95% CI 1.73‐11.32, P = 0.002). The heterogeneity was moderate (I2 = 66%), and the funnel plot suggested no significant publication bias. Subgroup analysis showed that the OR was 1.95 (95% CI 0.63–6.09) in studies using the lactulose breath test (LBT) and 7.60 (95% CI 3.50–16.50) in studies using the glucose breath test (GBT). The prevalence of SIBO in cirrhotic patients was also related to the severity of liver disease. Conclusions. Our meta‐analysis identified a strong association between SIBO and HE, and the risk of SIBO was 4.43 times higher among cirrhotic patients with HE than among those without HE. SIBO could be a predisposing factor for the development of HE in cirrhotic patients. Therefore, the importance of SIBO should be emphasized in patients with HE.
Impact of Different Solar Trackers on Hydrogen Production: A Case Study in Iran
Authors: Mostafaeipour Ali , Jahangiri Mehdi , Saghaei Hamed , Raiesi Goojani Afsaneh , Chowdhury Md. Shahariar , Techato Kuaanan
Published: October 2022

Currently, solar energy is considered one of the most suitable options for overcoming the problems of fossil fuel depletion, and global warming. Also, the high costs associated to photovoltaic systems, renders the maximum utilization of solar cells, a fundamental and undeniable necessity. Technical-economic-environmental analysis, using HOMER software, was performed under four different scenarios: without the tracker, with the horizontal axis tracker, with the vertical axis tracker, and with the dual-axis tracker. Consequently, the best configuration was chosen for each scenario. The optimal system for all four scenarios, in the circumstance of disconnection from the grid, only involves the solar cells, while in the circumstance of connection to the grid; both the solar cells and the wind turbine are included. The results demonstrate that in the off grid situation, the scenario involving the use of a vertical axis tracker would be the most cost-effective, with the price of 0.812 $/kWh for energy produced, while the lowest price for producing one kg of hydrogen is $77.97 is attributable to the scenario without the use of a solar tracker. In the circumstance of being connected to the power grid, the scenario involving the use of a vertical axis tracker would be most cost-effective, with the price of each kWh of energy produced equal to $ 0.223. At the price of $29.33 per kilogram, the scenario involving the use of a vertical axis tracker would also be most suitable for the production of hydrogen. Another important fact revealed through the results, is the crucial role of dump load, in the provision of the heat required in an off-grid situation. However, dump load is not associated to heat provision in a grid-connected situation.
Feasibility of Novel Magnetically Controlled Cable Capsule Endoscopy System In Vitro Experiments for Gastric Examination
Authors: Zhang Yaoping , Qu Lina , Gou Yani , Hao Jinyong , Huang Xiaojun
Published: October 2022

Background. Magnetically controlled capsule endoscopy has been shown to be feasible for the examination of gastric diseases. However, there may be problems, such as low image quality, incomplete esophageal observation, and capsule retention. We developed a novel magnetically controlled cable capsule endoscopy (MCCCE) system and evaluated its feasibility through in vitro experiments. Methods. Three experienced endoscopists performed MCCCE on the plastic stomach model and the excised porcine stomach model 5 times, respectively. Outcomes included handle ability, examination time, examination completion, and image quality. The examination completion was accessed by other two blinded endoscopists, and the image quality was compared with conventional gastroscopy (Olympus, GIF-290). Results. The performance of MCCCE in vitro experiments is excellent, with a mean operation time of 18.5 minutes in the plastic stomach model and 17.3 minutes in the excised porcine stomach model. The visualization rate of the gastric mucosa is >90% in the plastic stomach model and 75–90% in the excised porcine stomach model. The images of MCCCE are very clear, with good color resolution and no image distortion, which seem to be comparable to conventional gastroscopy. Conclusions. MCCCE system is feasible for gastric examination in vitro experiments, living animal experiments and human trials need to be further conducted.
MicroRNA 101 Attenuated NSCLC Proliferation through IDH2/HIFα Axis Suppression in the Warburg Effect
Authors: Han Le , Zhang Yili , Zhao Bin , Yue Jianren , Chen Zhenghong , Lei Guangyan , Huang Chen , Chen Wenjuan
Published: October 2022

Lung cancer is the most diagnosed and deadly cancer in China. MicroRNAs are small noncoding RNA gene products that exhibit multifunctional regulation in cancer cell progressions. MiR-101 loss was illustrated in about 29% of lung cancer patients, and sophisticated mechanisms of miR-101 regulation in NSCLC are eager to be disclosed. Here, using specimens from NSCLC patients and Dural-luciferase reporter assay, we got a clue that miR-101 correlated with IDH2. MiR-101 overexpression and IDH2 deficiency both suppressed NSCLC tumor growth in mice. Moreover, in NSCLC, miR-101 suppressed IDH2 expression levels, further increased α-KG concentration, and finally inhibited the Warburg effect under hypoxic conditions through downregulating HIF1α expression by promoting HIF1α hydroxylation and degradation. In conclusion, miR-101 attenuated the Warburg effect and NSCLC proliferation through IDH2/HIF1α pathway.
Jaundice on Presentation Is Associated with Higher In-Patient Mortality and Complications in Patients Admitted for Acute Pancreatitis: A Retrospective Study Based on National Inpatient Sample Database
Authors: Patel Nishit , Bodrya Krishna , Patel Kirten , Patel Nishi , Patel Dhruvanshu , Modi Ronak , Matin Ayaz
Published: October 2022

Pancreatitis usually presents with characteristic abdominal pain, radiological findings, and elevated lipase. The presence of jaundice may hint at a biliary etiology; however, it is not always present. We hypothesized that the presence of jaundice is associated with worse outcomes in patients admitted with pancreatitis. We conducted a retrospective analysis using the National Inpatient Sample, inquiring about patients admitted with pancreatitis with and without jaundice between October 2015 and December 2017. The primary outcome was in-hospital mortality in patients admitted for pancreatitis with and without jaundice. Secondary outcomes were the median length of stay, hospitalization cost, the incidence of ventilator-dependent respiratory failure (VDRF), acute respiratory distress syndrome (ARDS), sepsis, septic shock, dehydration and electrolyte disturbances, and ascites. A total of 1,267,744 patients were admitted with pancreatitis from October 2015 to December 2017. Among them, 8855 (0.7%) had concomitant jaundice on presentation. In-hospital mortality in this group was 4.3%. The patients with pancreatitis and jaundice had higher odds of in-hospital mortality (adjusted odds ratio [aOR]: 1.51, 99% CI 1.35–1.68,

p
<
0.0001

) as compared to those without jaundice. Patients with jaundice showed a significantly higher incidence of sepsis (15.2% vs. 9.6%,

p
<
0.0001

), septic shock (4.1% vs. 2.9%,

p
<
0.0001

), ascites (6.5% vs. 3.1%,

p
<
0.0001

), and dehydration and electrolyte disorders (47.6% vs. 43.8%,

p
<
0.0001

). Patients with jaundice also had higher total hospital costs ($11,412 vs. $7893,

p
<
0.0001

). There was no statistical difference in ARDS, VDRF, and median length of stay. In conclusion, patients admitted for pancreatitis with jaundice had worse outcomes, including in-hospital mortality and complications, compared to those without jaundice.
An Initial Survey on the Prevalence of Group B Streptococcus (GBS) among Yemeni Pregnant Women in Sana’a City
Authors: Al-Subol Ibrahim , Abdul-Aziz Maha , Almikhlafy Abdullah A. , Alqahtani Talal
Published: October 2022

Background. Infection with group B Streptococcus (GBS) is still a neonatal life-threatening illness, especially in developing countries such as Yemen. Objective. This study was aimed at determining the vaginal colonization rate and antibiotic susceptibility pattern of GBS among Yemeni pregnant women. Methods. We conducted a cross-sectional study over a four-month period involving 210 pregnant women at the 35th to 39th gestational weeks who visited Gaza medical center in Sana’a city, Yemen. The collected vaginal swab specimen was inoculated in the Todd-Hewitt enrichment broth and incubated for 24 h and then subcultured on a 5% human blood agar plate. All positive cultures identified as GBS were subjected to antibiotic susceptibility tests using the disk diffusion method. Results. Out of 210 recruited pregnant women, 23 (10.95%) were GBS vaginal carriers. All GBS isolates were sensitive to penicillin, ampicillin, levofloxacin, cefotaxime, and vancomycin. Conclusion. Based on the study’s results, approximately eleven out of every 100 pregnant women in Sana’a city are vaginally colonized by GBS. Beta-lactam antibiotics remain the drug of choice to treat and prevent GBS infections. A prenatal screening policy is urgently needed for Yemeni pregnant women.
A Nomogram for Predicting Cardiovascular Diseases in Chronic Obstructive Pulmonary Disease Patients
Authors: Qu Shuang , Zhu Jing
Published: October 2022

Cardiovascular diseases (CVDs) are the most common comorbidities in the chronic obstructive pulmonary disease (COPD), which increase the risk of hospitalization, length of stay, and death in COPD patients. This study aimed to identify the predictors for CVDs in COPD patients and construct a prediction model based on these predictors. In total, 1022 COPD patients in National Health and Nutrition Examination Surveys (NHANES) were involved in the cross-sectional study. All subjects were randomly divided into the training set (n = 709) and testing set (n = 313). The differences before and after the manipulation of the missing data were compared via sensitivity analysis. Univariate and multivariable analyses were employed to screen the predictors of CVDs in COPD patients. The performance of the prediction model was evaluated via the area under the curve (AUC), accuracy, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and calibration. Subgroup analysis was performed in patients using different COPD diagnosis methods and patients smoking or not smoking in the testing set. We found that male, older age, a smoking history, overweight, a history of blood transfusion, a history of heart disease in close relatives, higher levels of white blood cell (WBC), and monocyte (MONO) were associated with the increased risk of CVDs in COPD patients. Higher levels of platelets (PLT) and lymphocyte (LYM) were associated with reduced risk of CVDs in COPD patients. A prediction model for the risk of CVDs in COPD patients was established based on predictors including gender, age, a smoking history, BMI, a history of blood transfusion, a history of heart disease in close relatives, WBC, MONO, PLT, and LYM. The AUC value of the prediction model was 0.75 (95% CI: 0.71–0.79) in the training set and 0.79 (95%CI: 0.73–0.85) in the testing set. The prediction model established showed good predictive performance in predicting CVDs in COPD patients.
Identifying Hub Genes and Immune Cell Infiltration for the Progression of Carotid Atherosclerotic Plaques in the Context of Predictive and Preventive Using Integrative Bioinformatics Approaches and Machine-Learning Strategies
Authors: Zhang Han , Huang Yinde , Li Xin , Chen Wenbin , Lun Yu , Zhang Jian
Published: October 2022

Emerging evidence shows that carotid atherosclerosis is related to the activation of immune-related pathways and inflammatory cell infiltration. However, the immune-linked pathways that helped in the advancement of the carotid atherosclerotic plaque and the association of such plaques with the infiltration status of the body’s immune cells still unclear. Here, the expression profiles of the genes expressed during the progression of the carotid atherosclerotic plaques were retrieved from the Gene Expression Omnibus database and 178 differentially expressed genes were examined. The Weighted Gene Coexpression Network Analysis technique identified one of the brown modules showed the greatest correlation with carotid atherosclerotic plaques. In total, 66 intersecting genes could be detected after combining the DEGs. LASSO regression analysis was subsequently performed to obtain five hub genes as potential biomarkers for carotid atherosclerotic plaques. The functional analysis emphasized the vital roles played by the inflammation- and immune system-related pathways in this disease. The immune cell infiltration results highlighted the significant correlation among the CD4+ T cells, B cells, macrophages, and CD8+ T cells. Thereafter, the gene expression levels and the diagnostic values related to every hub gene were further validated. The above results indicated that macrophages, B cells, CD4+ T cells, and CD8 + T cells were closely related to the formation of the advanced-stage carotid atherosclerotic plaques. Based on the results, it could be hypothesized that the expression of hub genes (C3AR1, SLAMF8, TMEM176A, FERMT3, and GIMAP4) assisted in the advancement of the early-stage to advanced-stage carotid atherosclerotic plaque through immune-related signaling pathways. This may help to provide novel strategies for the treatment of carotid plaque in the context of predictive, preventive, and personalized medicine.
Relationship of Serum IL-12 to Inflammation, Hematoma Volume, and Prognosis in Patients With Intracerebral Hemorrhage
Authors: Zhang Yazhao , Tian Yanan , Wei Jianhui , Xiang Yi
Published: October 2022

Objective. Inflammatory cascades and hematomas after intracerebral hemorrhage (ICH) cause brain tissue and neuronal damage. Interleukin-12 (IL-12) promotes brain inflammation, and regulates coagulation mediated by red blood cells and platelets. This study was designed to investigate the relationship of serum IL-12 to inflammation, hematoma volume, and prognosis in ICH patients. Methods. We recruited patients with ICH within 12 hours of symptom onset (n = 209) and measured their serum IL-12 levels. Patients with an increased National Institute of Health stroke scale (NIHSS) score ≥4 were defined as early neurological deterioration, and modified rankin scale (mRS) score >2 at 3 months after intracerebral hemorrhage was defined as poor prognosis. Results. Levels of serum IL-12 was positively correlated with the admission of NIHSS scores (r = 0.535,

P
<
0.001

), hematoma volume (r = 0.608,

P
<
0.001

), serum CRP levels (r = 0.561,

P
<
0.001

), and serum TNF-α levels (r = 0.533,

P
<
0.001

) in 209 cases ICH patients. Levels of IL-12 in ICH patients with early neurological deterioration (median: 82.9 versus 65.8,

P
<
0.001

) or with poor prognosis (median: 79.0 versus 65.3,

P
<
0.001

) were all significantly higher than those in other ICH patients. In addition, serum IL-12 levels could be used to differentiate ICH patients at risk for early neurological deterioration with an AUC of 0.788 (95% CI: 0.717–0.858) or ICH patients at risk for suffering from an unfavorable outcome with an AUC of 0.787 (95% CI: 0.722–0.851). Conclusion. Elevated admission serum IL-12 levels are closely related to the inflammation, hematoma volume, and prognosis in ICH patients. Substantializing serum IL-12 levels is a prognostic biomarker for ICH.
The Combination of Individual Herb of Mi-Jian-Chang-Pu Formula Exerts a Synergistic Effect in the Treatment of Ischemic Stroke in Rats
Authors: Lu Fangfang , Su Xiaojuan , Liu Jingjing , Zong Rong , Ding Shuqin , Yang Lingling , Liu Jing , Wilson Gidion , Li Liuyan , Yang Youyue , Wang Xiaoying , Wang Weibiao , Ma Xueqin
Published: October 2022

Mi-Jian-Chang-Pu formula (MJCPF), composed of Crocus sativus L. and Acorus tatarinowii Schott, is a well-known TCM for treatment of hemiplegia, facial paralysis as well as language dysfunction caused by stroke both in ancient and modern times. By using pharmacodynamics, pharmacokinetics, and metabolomics, our present study discusses whether the combination of individual herbs or major active components of MJCPF possess synergistic neuroprotective effects against ischemic stroke (IS). 108 adult male Sprague-Dawley rats were randomly and equally divided into 9 groups, including sham group (N, vehicle), middle cerebral artery occlusion (MCAO) model group (M, vehicle), positive group (P, 36 mg/kg/day nimodipine), crocin I (A1, 40 mg/kg/day), β-asarone (B1, 15 mg/kg/day), crocin I + β-asarone (A1B1, 55 mg/kg/day), C. sativus (A, 580 mg/kg/day), A. tatarinowii (B, 480 mg/kg/day), and C. sativus + A. tatarinowii, also named MJCPF (AB, 1060 mg/kg/day) groups. All drugs were orally administered to rats once a day for 14 consecutive days. Neurological deficit score, cerebral infarct volume, body weight change, TTC, HE and IHC staining, behavioral evaluation, metabolic profiles, and pharmacokinetic parameters were determined. MCAO led to severe brain damage including large infarct volume, more severe brain tissue injury, and worse neurological function as compared to the sham rats. All treatment groups showed a significant neuroprotective effect on MCAO rats. Furthermore, the pharmacodynamics’ results demonstrated that MJCPF had a synergistic effect evidenced by small infarct volume, more regular arrangement of neuronal cells, and more improved neural function, and the levels of inflammatory factors were closer to normality. A total of 53 differential metabolites between MCAO and sham groups were screened by integration of serum and brain metabolisms, all of which were restored at varying degrees in treatment. PCA and PLS-DA analysis showed that the levels of differential metabolites treated with MJCPF were closer to the sham group than the individual herb and single compound alone or A1B1 combination. The pharmacokinetic parameters further verified the above results that MJCPF could synergistically promote drug absorption greater than others. Our integrated pharmacodynamics, metabolomics, and pharmacokinetic approach reveals the synergistic effect of MJCPF on treatment of IS, which powerfully contribute to the understanding of scientific connotation of TMC formula.
A Phase II Clinical Trial of Nivolumab and Temozolomide for Neuroendocrine Neoplasms
Authors: Owen Dwight H. , Benner Brooke , Wei Lai , Sukrithan Vineeth , Goyal Ashima , Zhou Ye , Pilcher Carly , Suffren Sheryl-Ann , Christenson Gwen , Curtis Nancy , Jukich Megan , Schwarz Emily , Savardekar Himanshu , Norman Ruthann , Ferguson Sarah , Kleiber Barbara , Wesolowski Robert , Carson William E. , Otterson Gregory A. , Verschraegen Claire F. , Shah Manisha H. , Konda Bhavana
Published: October 2022

Purpose:

Treatment options are limited in patients with metastatic neuroendocrine neoplasms (NEN). We present the results for a phase II trial of combination nivolumab and temozolomide in patients with advanced NEN along with results of immune changes in peripheral blood.

Patients and Methods:

NCT03728361 is a nonrandomized, phase II study of nivolumab and temozolomide in patients with NEN. The primary endpoint was response rate using RECIST 1.1. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. Immune profiling was performed by mass cytometry to evaluate the effect on peripheral blood immune cell subsets.

Results:

Among all 28 patients with NEN, the confirmed response rate was 9/28 [32.1%, 95% confidence interval (CI): 15.9–52.4]. Of 11 patients with lung NEN, the response rate was 64% (n = 7); there was a significant difference in responses by primary tumor location (lung vs. others, P = 0.020). The median PFS was 8.8 months (95% CI: 3.9–11.1 months), and median OS was 32.3 months (95% CI: 20.7—not reached months). Exploratory blood immune cell profiling revealed an increase in circulating CD8+ T cells (27.9% ± 13.4% vs. 31.7% ± 14.6%, P = 0.03) and a decrease in CD4+ T cells (59.6% ± 13.1% vs. 56.5% ± 13.0%, P = 0.001) after 2 weeks of treatment. LAG-3–expressing total T cells were lower in patients experiencing a partial response (0.18% ± 0.24% vs. 0.83% ± 0.55%, P = 0.028). Myeloid-derived suppressor cell levels increased during the study and did not correlate with response.

Conclusions:

Combination nivolumab and temozolomide demonstrated promising activity in NEN.

See related commentary by Velez and Garon, p. 691
Favorable Activity and Safety Profile of Memory-Enriched CD19-Targeted Chimeric Antigen Receptor T-Cell Therapy in Adults with High-Risk Relapsed/Refractory ALL
Authors: Aldoss Ibrahim , Khaled Samer K. , Wang Xiuli , Palmer Joycelynne , Wang Yan , Wagner Jamie R. , Clark Mary C. , Simpson Jennifer , Paul Jinny , Vyas Vibhuti , Chien Sheng-Hsuan , Stein Anthony , Pullarkat Vinod , Salhotra Amandeep , Al Malki Monzr M. , Aribi Ahmed , Sandhu Karamjeet , Thomas Sandra H. , Budde Lihua E. , Marcucci Guido , Brown Christine E. , Forman Stephen J.
Published: October 2022

Purpose:

A phase I/II study evaluating the safety and activity of memory-enriched CD19-directed chimeric antigen receptor (CD19-CAR) T cells in adults with relapsed/refractory B-cell acute lymphoblastic leukemia (ALL).

Patients and Methods:

In phase I, we tested sequentially two cell populations for CAR transduction: (i) central memory (Tcm) or (ii) naïve, stem, and central memory (Tn/mem) T cells. The study employed an activity constrained for toxicity design to determine the recommended phase II dose (RP2D), which was tested in phase II.

Results:

The Tcm cohort was closed early due to lack of activity. The 200 ×106 Tn/mem-derived CD19-CAR T-cell dose was found to be safe and active, and was declared the RP2D. At RP2D, 58 participants underwent leukapheresis and 46 received CD19-CAR T cells. Median age for treated participants was 38 years (range, 22–72). Twenty-nine (63%) participants had relapsed post-allogeneic hematopoietic cell transplantation (alloHCT), 18 (39%) had Philadelphia-like (Ph-like) genotype, and 16 (35%) had extramedullary disease (EMD) at lymphodepletion (LD). Three (7%) participants had grade 3 cytokine release syndrome (CRS), and none had grade ≥ 4 CRS. Eight (17%) participants had grade ≥ 3 neurotoxicity, including one fatal cerebral edema. Forty (87%) patients achieved complete remission (CR)/CR with incomplete hematologic recovery, 2 (4%) progressed, and 4 (9%) were unevaluable for response. Among 42 response-evaluable participants, 16/17 with Ph-like ALL and 13/15 with EMD at LD responded. Twenty-one (53%) responders underwent alloHCT consolidation, which was associated with improved relapse-free survival (adjusted HR = 0.16; 95% confidence interval, 0.05–0.48; P = 0.001).

Conclusions:

Tn/mem-derived CD19-CAR T cells were safe and active, including in Ph-like ALL and EMD.

See related commentary by El Marabti and Abdel-Wahab, p. 694
Abstract 9848: Image Guided Computational Model of the Mitral Valve in Heart Failure with Functional Mitral Regurgitation - A Platform for Preclinical Procedure Planning
Authors: Gaidulis Gediminas , Padala Muralidhar
Published: October 2022

Introduction:
Therapeutic benefit of correcting functional mitral regurgitation (FMR) is increasingly recognized, since positive results from COAPT trial indicate a significant reduction in hospitalization rate and mortality. However, this benefit is strongly dependent on the extent of reduction in FMR with the MitraClip system, which is often variable and unpredictable. We report a patient-specific, 3D echo derived computational model of the mitral valve that faithfully mimics the FMR-like valve for procedure planning.

Methods:
FMR datasets were obtained in two pigs that received a myocardial infarction via percutaneous occlusion of the left circumflex artery. 3D echo was performed 3 months after infarction, and images were segmented to obtain annular and leaflet geometry, and papillary muscle (PM) locations in the ventricle. Chordal distribution was developed
(Fig. A)
based on anatomical measurements in hearts as they are not visible on echo. The PMs were sub-divided into three heads with marginal, strut and basal chordae emerging from these heads as seen in real hearts
(Fig. B)
. In FMR state, the PM locations are displaced, imposing a pre-strain on the chordae. Valve closure simulation was modeled by pre-straining the chordae and applying transvalvular pressure gradient on the leaflets, and stress analysis was performed.

Results:
Agreement in the truth dataset (echo image) and the model (simulated data) are shown in
Fig. C
, indicating fidelity of the model. Peak stresses were observed on A2 and P2 segments near the strut chordae insertion regions with maximum values of 7.62 and 4.93 MPa for each dataset
(Fig. D)
, which corresponds well with the previously reported findings.

Conclusions:
A proposed FMR modeling workflow allowed to obtain a realistic systolic configuration of the mitral valve. Such models may be used to virtually implement various FMR repair techniques, allowing to predict post-repair outcomes and optimize FMR repair at a patient-specific level.
Current Approach to the Diagnosis of Sarcopenia in Heart Failure: A Narrative Review on the Role of Clinical and Imaging Assessments
Authors: Mirzai Saeid , Eck Brendan L. , Chen Po-Hao , Estep Jerry D. , Tang W.H. Wilson
Published: October 2022

Sarcopenia has been established as a predictor of poor outcomes in various clinical settings. It is particularly prevalent in heart failure, a clinical syndrome that poses significant challenges to health care worldwide. Despite this, sarcopenia remains overlooked and undertreated in cardiology practice. Understanding the currently proposed diagnostic process is paramount for the early detection and treatment of sarcopenia to mitigate downstream adverse health outcomes.
Salt Sensitivity of Blood Pressure in Women
Authors: Barris Candee T. , Faulkner Jessica L. , Belin de Chantemèle Eric J.
Published: October 2022

Several clinical and large population studies indicate that women are more salt-sensitive than men, yet the precise mechanisms by which the sexually dimorphic onset manifests remains incompletely understood. Here, we evaluate recent epidemiological data and highlight current knowledge from studies investigating sex-specific mechanisms of salt-sensitive blood pressure (SSBP). Emerging evidence indicates that women of all ethnicities are more salt-sensitive than men, at all ages both premenopausal and postmenopausal. However, menopause exacerbates severity and prevalence of SSBP, suggesting that female sex chromosomes predispose to and female sex hormones mitigate SSBP. Results from both human and rodent studies support the contribution of enhanced and inappropriate activation of the aldosterone-ECMR (endothelial cell mineralocorticoid receptor) axis promoting vascular dysfunction in females. Increases in adrenal response to angiotensin II, in association with higher ECMR expression and activation of endothelial ENaC (epithelial sodium channel) in females compared to males, are emerging as central players in the development of endothelial dysfunction and SSBP in females. Female sex increases the prevalence and susceptibility of SSBP and sex hormones and sex chromosome complement may exert antagonistic effects in the development of the female heightened SSBP.
Risk of Hypertensive Disorders in Pregnancy After Fresh and Frozen Embryo Transfer in Assisted Reproduction: A Population-Based Cohort Study With Within-Sibship Analysis
Authors: H. Petersen Sindre , Westvik-Johari Kjersti , Spangmose Anne Lærke , Pinborg Anja , Romundstad Liv Bente , Bergh Christina , Åsvold Bjørn Olav , Gissler Mika , Tiitinen Aila , Wennerholm Ulla-Britt , Opdahl Signe
Published: October 2022

Background:

Frozen embryo transfer (frozen-ET) is increasingly common because of improved cryopreservation methods and elective freezing of all embryos. Frozen-ET is associated with higher risk of hypertensive disorders in pregnancy than both natural conception and fresh embryo transfer (fresh-ET), but whether this is attributable to parental factors or treatment is unknown.

Methods:

Using the Medical Birth Registries of Denmark (1994–2014), Norway, and Sweden (1988–2015), linked to data from national quality registries and databases on assisted reproduction, we designed a population-based cohort study with within-sibship comparison. We included 4 426 691 naturally conceived, 78 300 fresh-ET, and 18 037 frozen-ET singleton pregnancies, of which 33 209 sibships were conceived using different conception methods. Adjusted odds ratios (aOR) of hypertensive disorders in pregnancy for fresh-ET and frozen-ET versus natural conception with 95% CI were estimated using multilevel logistic regression, where random effects provided conventional population-level estimates and fixed effects gave within-sibship estimates. Main models included adjustment for birth year, maternal age, parity, and country.

Results:

Risk of hypertensive disorders in pregnancy was higher after frozen-ET compared to natural conception, both at population-level (7.4% versus 4.3%, aOR, 1.74 [95% CI, 1.61–1.89]) and within sibships (aOR, 2.02 [95% CI, 1.72–2.39]). For fresh-ET, risk was similar to natural conception, both at population-level (aOR, 1.02 [95% CI, 0.98–1.07]) and within sibships (aOR, 0.99 [95% CI, 0.89–1.09]).

Conclusions:

Frozen-ET was associated with substantially higher risk of hypertensive disorders in pregnancy, even after accounting for shared parental factors within sibships.
Systolic Blood Pressure Time in Target Range and Major Adverse Kidney and Cardiovascular Events
Authors: Buckley Leo F. , Baker William L. , Van Tassell Benjamin W. , Cohen Jordana B. , Alkhezi Omar , Bress Adam P. , Dixon Dave L.
Published: October 2022

Background:

Whether time-in-target range (TTR) for systolic blood pressure (SBP) associates with adverse kidney and cardiovascular events remains incompletely understood.

Methods:

This study included participants in 2 clinical trials that compared intensive (<120 mm Hg) and standard (<140 mm Hg) SBP lowering. SBP-TTR for months 0 to 3 was calculated using therapeutic ranges of 110 to 130 mm Hg and 120 to 140 mm Hg for the intensive and standard arms, respectively. Adverse kidney events included the composite of dialysis, kidney transplant, serum creatinine >3.3 mg/dL, sustained eGFR <15 mL/(min·1.73 m
2
), or sustained eGFR decline >40%. Adverse cardiovascular events included myocardial infarction, stroke, heart failure, and cardiovascular death. Adjusted Cox proportional hazards regression models were used to estimate the association between SBP-TTR and kidney and cardiovascular events.

Results:

Participants with higher TTR were younger and less likely to have preexisting cardiovascular disease. Compared with participants with TTR of 0%, the risk of adverse kidney events was lower for participants with TTR of >0% to 43% (hazard ratio [95% CI], 0.57 [0.42–0.76];
P
<0.001), 43% to <70% (0.57 [0.42–0.78];
P
=0.001), 70% to <100% (0.53 [0.38–0.74];
P
<0.001), and 100% (0.33 [0.20–0.57];
P
<0.001) in fully adjusted models. The risk of major adverse cardiovascular events was lower for participants with TTR of >0% to 43% (0.66 [0.52–0.83];
P
=0.001), 43% to <70% (0.70 [0.55–0.90];
P
=0.005), 70% to <100% (0.65 [0.50–0.84];
P
=0.001), or 100% (0.56 [0.39–0.80];
P
=0.001) compared with those with TTR of 0%.

Conclusions:

Higher SBP-TTR associates with lower risks of adverse kidney and cardiovascular events in adults with hypertension. SBP-TTR may be a potential therapeutic target and quality metric.
Holy Healers in Rome
Authors: Lourié Basil , Lidova Maria
Published: October 2022

The article is dedicated to four saints represented in the Chapel of Holy Physicians in Santa Maria Antiqua church in Rome. Two saints are identified for the first time (Jonas and Procopius), one previously hypothetical identification is confirmed (Barachisius), and the meaning of the cult of St Dometius in Rome is discussed. The hagiographical dossier of Sts Jonas and Barachisius is examined in detail. Based on this examination, it is argued that the earliest recensions of their martyrdom must go back to the Syriac Chalcedonian archetype written in the 590s, which, in turn, derived from a Syriac “Nestorian” hagiographical work produced in sixth-century Iran and related to the mid-sixth-century rebellion of prince Anōšazād against his father Khosrow I. The Chalcedonian counterpart of this lost hagiographical work was paraphrased by Ferdowsi.
Introduction: The Production and Distribution of Sino-European Intercultural Books in China (1582–c.1823)
Authors: Standaert Nicolas
Published: October 2022

A unique characteristic of the cultural contacts between China and Europe in the seventeenth and eighteenth centuries is the intercultural circuit of books that was established: European books travelling to China, and in return Chinese books travelling to Europe. Within this circuit, a large number of intercultural books was translated and published in Chinese or in European languages, thus becoming the source material for new publications. This special issue of EAPS focuses on the Chinese pole of this cross-continental textual exchange, where the printing of Sino-European books was facilitated by the presence of a well-established print culture. By analysing a unique collection of these Sino-European books, the following two articles investigate their production and distribution from the late Ming until the mid-Qing period (1582–c.1823). As such, they provide insights into the emergence of an intercultural ‘book world’. The following introduction sets the scene for the two articles.
Threat or Godsend? Evangelicals and Democracy in Latin America
Authors: Blanton Matthew
Published: October 2022

While Protestant and Evangelical groups started as small minorities in Latin America, they have recently experienced explosive growth and now make up a large proportion of the region’s religious faithful. This unexpected shift led to a spate of scholarship speculating as to how the new Evangelical communities would impact society. Given the perennial concern over the health of democracy in Latin America, much of this work focused on how Evangelicals might differ from Catholics in terms of support for democratic values and civic participation. Some predicted that Evangelicals would be eager supporters of democracy and an active, positive force in the community. Others warned that Evangelicals were too focused on spiritual matters, which would lead to apathy and a passive acceptance of authoritarianism. This paper uses recent survey data from sixteen nations in Latin America to test these theories with the goal of answering the question: are Evangelicals a threat or godsend for democracy in Latin America?
Maria in de Syrische Kerk
Authors: Ploeg O.P. J. v. d.
Published: October 2022

Le présent article rappelle quelques traits de la dévotion mariale dans les Eglises de langue syriaque. La liturgie de la Messe mentionne assez rarement la Vierge Marie; mais à mesure quʼon sʼapproche de Constantinople, ces mentions se multiplient; cʼest la Messe maronite qui en contient le plus grand nombre. Aphraate appelle Marie „bienheureuse” et il la compare à Eve, mais pour le reste il en parle fort peu, Pour défendre la valeur de la virginité et la vie célibataire, il fait appel, non à Marie, mais aux saints de lʼAncien Testament (Moïse, Jérémie, Elie et dʼautres)! S. Ephrem est le premier grand poète en langue syriaque et ses hymnes témoignent dʼune vénération particulière pour la Vierge, dont il exalte surtout la virginité. Lʼauthenticité des hymnes en question a été mise en doute, mais les raisons sont loin dʼêtre décisives. Le caractère authentique dʼau moins le plus grand nombre dʼentre eux semble assez certain. Le parallélisme Eve-Marie est pleinement développé chez Ephrem, et il connaît déjà presque tous les symboles courants de la virginité de la mère de Dieu, que les Pères ont trouvés dans LʼAncien Testament.

Jacques de Saroug a longuement développé les thèmes marials traités par S. Ephrem. Comme les autres Pères, il défend la triple virginité de Marie: ante, in et post partum, mais il ne semble pas quʼil ait admis que Marie nʼa pas connu Jes douleurs de lʼenfantement. Bien que la bienheureuse vierge ait été délivrée de la malédiction de Gen. III 16, il semble quʼelle ait quand-même connu quelques douleurs, comme son Fils les a connues également.
De Kerk van Rome en de Oosterse Kerken
Authors: van Montfoort A.A. E.
Published: October 2022

L’Eglise de Rome et les Eglises Orientales

L’article traite des principaux contacts qu’a eus depuis son élection S.S. Paul VI avec S.S. le Patriarche Oecuménique, Athénagoras Ier. Ensuite l’auteur donne un compte-rendu des rencontres du Saint Père avec les patriarches Benedictos, Derderian et Athénagoras et avec la hiérarchie des églises orientates unies lors du pélerinage du pape à Jérusalem. - L’article donne le texte intégral des discours prononcés.
How do Visit Facilitation and Accessibility of Prisons Relate to Visits from Professionals and Volunteers?
Authors: Pasma Amanda J , van Ginneken Esther , Palmen Hanneke , Nieuwbeerta Paul
Published: October 2022

Reintegration support by community-based professionals and volunteers (CBPs) is needed to prepare prisoners for release. Yet, the way in which CBPs are received, informed and accommodated, may hamper in-prison involvement. Therefore, the current study explores the visit facilitation and accessibility of prisons in the Netherlands as experienced by CBPs. A new instrument to measure facilitation and accessibility across institutions is introduced. The findings among 4,309 prisoners and 1,077 professionals across 24 Dutch prisons revealed that although institutions differ in facilitation and accessibility, this is unrelated to prison visits received from most CBPs, apart from the likelihood of receiving visits from parole officers. The study confirms the importance of considering facilitation and accessibility in relation to in-prison involvement of external agencies.
New evidence for Hipparchus’ Star Catalogue revealed by multispectral imaging
Authors: Gysembergh Victor , J. Williams Peter , Zingg Emanuel
Published: October 2022

New evidence for ancient Greek astronomer Hipparchus’ lost Star Catalogue has come to light thanks to multispectral imaging of a palimpsest manuscript and subsequent decipherment and interpretation. This new evidence is the most authoritative to date and allows major progress in the reconstruction of Hipparchus’ Star Catalogue. In particular, it confirms that the Star Catalogue was originally composed in equatorial coordinates. It also confirms that Ptolemy’s Star Catalogue was not based solely on data from Hipparchus’ Catalogue. Finally, the available numerical evidence is consistent with an accuracy within 1° of the real stellar coordinates, which would make Hipparchus’ Catalogue significantly more accurate than his successor Claudius Ptolemy’s.
Determination of Factors Affecting the Adoption of Integrated Farming System in Dryland Areas of Southern India by Using Supervised Learning Techniques
Authors: Kandasamy Sathya Uma Lakshmi , Singh Piyush Kumar , Swain Dillip Kumar
Published: October 2022

Smallholders of dryland ecosystems continue to live below the poverty line while facing significant economic and social deprivation with decreasing landholding. Most dryland farmers perform conventional disintegrated farming practices due to a lack of knowledge and resource inefficiency. This study investigates the possibility of an Integrated Farming System (IFS) to address the current dryland farming issues and explore various factors affecting its adoption among the farming community. This study aims to apply and compare supervised learning techniques to assess the primary drivers affecting the adoption of the IFS in rural southern India. The study shows that organic fertilizer production, farmers’ age, and involvement in the extension activity are the major factors affecting the adoption of IFS among dryland farmers. The study supports that small and marginal farmers have a high possibility of realizing the higher benefit from IFS. The study recommends that these components be given proper policy consideration in designing and implementing an effective farming system in dryland areas to improve farmers’ income levels.
The wedding bells of war: The influence of armed conflict on child marriages in West Africa
Authors: DiGiuseppe Matthew , Haer Roos
Published: October 2022

Child marriage is a fundamental violation of human rights. It hinders progress towards development and public health goals. In this study, we argue that armed conflict plays an important role in the occurrence of child marriages; it influences the supply of and demand for young brides. We argue that in conflict settings, families are more willing to marry off their young daughters for protection. Armed conflict can also influence the demand: marriage in general declines due to an imbalance in sex ratio. However, in cases where belligerents use war tactics specifically focused on harming girls, such as sexual violence and girl recruitment, early marriage might increase as the result of armed conflict. To empirically examine these linkages, we combine the Demographic and Health Surveys of West Africa with information on the location of armed conflict. Our study shows that armed conflict generally reduces the occurrence of child marriage with 13% to 18%. However, we observe that when conflict actors use war tactics that specifically harm young girls there is a significant increase of 12% to 18% in the probability of a girl getting married before the age of 18. This research has important implications for our understanding of the relationship between armed conflict, gender inequality, and their impact on children.