bluuebunny/crossref_metadata_2025 huggingface dataset:
Adipose-derived mesenchymal stem cells attenuate dialysis-induced peritoneal fibrosis by modulating macrophage polarization via interleukin-6
Authors: Yang Chih-Yu , Chang Pu-Yuan , Chen Jun-Yi , Wu Bo-Sheng , Yang An-Hang , Lee Oscar Kuang-Sheng
Published: March 2021

Background

Life-long peritoneal dialysis (PD) as a renal replacement therapy is limited by peritoneal fibrosis. Previous studies showed immunomodulatory and antifibrotic effects of adipose-derived mesenchymal stem cells (ADSCs) on peritoneal fibrosis. However, the role of the peritoneal macrophage in this process remains uninvestigated.

Methods

We examined the therapeutic effects of ADSC and bone marrow-derived mesenchymal stem cells (BM-MSC) in the rat model of dialysis-induced peritoneal fibrosis using methylglyoxal. In addition, treatment of macrophages with the conditioned medium of ADSC and BM-MSC was performed individually to identify the beneficial component of the stem cell secretome.

Results

In the in vivo experiments, we found dialysis-induced rat peritoneal fibrosis was attenuated by both ADSC and BM-MSC. Interestingly, ADSC possessed a more prominent therapeutic effect than BM-MSC in ameliorating peritoneal membrane thickening while also upregulating epithelial cell markers in rat peritoneal tissues. The therapeutic effects of ADSC were positively associated with M2 macrophage polarization. In the in vitro experiments, we confirmed that interleukin-6 (IL-6) secreted by MSCs upon transforming growth factor-β1 stimulation promotes M2 macrophage polarization.

Conclusions

In dialysis-induced peritoneal fibrosis, MSCs are situated in an inflammatory environment of TGF-β1 and secrete IL-6 to polarize macrophages into the M2 phenotype. Our findings reveal a previously unidentified role of tissue macrophage in this antifibrotic process. ADSC has the advantage of abundance and accessibility, making the application values extremely promising.

Graphical abstract

In dialysis-induced peritoneal fibrosis, peritoneal mesothelial cells secrete transforming growth factor-β1 (TGF-β1) when exposed to methylglyoxal (MGO)-containing peritoneal dialysate. When situated in TGF-β1, the inflammatory environment induces mesenchymal stem cells to secrete interleukin-6 (IL-6), IL-6 polarizes macrophages into the M2 phenotype. The dominant peritoneal tissue M2 macrophages, marked by upregulated Arg-1 expression, account for the attenuation of MGO-induced dedifferentiation of peritoneal mesothelial cells to maintain epithelial integrity.
Hypersurfaces of a Sasakian manifold - revisited
Authors: Deshmukh Sharief , Belova Olga , Turki Nasser Bin , Vîlcu Gabriel-Eduard
Published: March 2021

We study orientable hypersurfaces in a Sasakian manifold. The structure vector field ξ of a Sasakian manifold determines a vector field v on a hypersurface that is the component of the Reeb vector field ξ tangential to the hypersurface, and it also gives rise to a smooth function σ on the hypersurface, namely the projection of ξ on the unit normal vector field N. Moreover, we have a second vector field tangent to the hypersurface, given by $\mathbf{u}=-\varphi (N)$
u
=
−
φ
(
N
)
. In this paper, we first find a necessary and sufficient condition for a compact orientable hypersurface to be totally umbilical. Then, with the assumption that the vector field u is an eigenvector of the Laplace operator, we find a necessary condition for a compact orientable hypersurface to be isometric to a sphere. It is shown that the converse of this result holds, provided that the Sasakian manifold is the odd dimensional sphere $\mathbf{S}^{2n+1}$

S

2
n
+
1

. Similar results are obtained for the vector field v under the hypothesis that this is an eigenvector of the Laplace operator. Also, we use a bound on the integral of the Ricci curvature $Ric ( \mathbf{u},\mathbf{u} ) $
R
i
c
(
u
,
u
)
of the compact hypersurface to find a necessary condition for the hypersurface to be isometric to a sphere. We show that this condition is also sufficient if the Sasakian manifold is $\mathbf{S}^{2n+1}$

S

2
n
+
1

.
Uniqueness and concentration for a fractional Kirchhoff problem with strong singularity
Authors: Yu Shengbin , Chen Jianqing
Published: March 2021

In this paper, we consider the following fractional Kirchhoff problem with strong singularity: $$ \textstyle\begin{cases} (1+ b\int _{\mathbb{R}^{3}}\int _{\mathbb{R}^{3}} \frac{ \vert u(x)-u(y) \vert ^{2}}{ \vert x-y \vert ^{3+2s}}\,\mathrm{d}x \,\mathrm{d}y )(-\Delta )^{s} u+V(x)u = f(x)u^{-\gamma }, & x \in \mathbb{R}^{3}, \\ u>0,& x\in \mathbb{R}^{3}, \end{cases} $$

{

(
1
+
b

∫

R
3

∫

R
3

|
u
(
x
)
−
u
(
y
)

|
2

|
x
−
y

|

3
+
2
s

d
x

d
y
)

(
−
Δ
)

s

u
+
V
(
x
)
u
=
f
(
x
)

u

−
γ

,

x
∈

R
3

,

u
>
0
,

x
∈

R
3

,

where $(-\Delta )^{s}$

(
−
Δ
)

s

is the fractional Laplacian with $0< s<1$
0
<
s
<
1
, $b>0$
b
>
0
is a constant, and $\gamma >1$
γ
>
1
. Since $\gamma >1$
γ
>
1
, the energy functional is not well defined on the work space, which is quite different with the situation of $0<\gamma <1$
0
<
γ
<
1
and can lead to some new difficulties. Under certain assumptions on V and f, we show the existence and uniqueness of a positive solution $u_{b}$

u
b

by using variational methods and the Nehari manifold method. We also give a convergence property of $u_{b}$

u
b

as $b\rightarrow 0$
b
→
0
, where b is regarded as a positive parameter.
A Kirchhoff-type problem involving concave-convex nonlinearities
Authors: Gao Yuan , Liu Lishan , Luan Shixia , Wu Yonghong
Published: March 2021

A Kirchhoff-type problem with concave-convex nonlinearities is studied. By constrained variational methods on a Nehari manifold, we prove that this problem has a sign-changing solution with least energy. Moreover, we show that the energy level of this sign-changing solution is strictly larger than the double energy level of the ground state solution.
Analysis of Atangana–Baleanu fractional-order SEAIR epidemic model with optimal control
Authors: Deressa Chernet Tuge , Duressa Gemechis File
Published: March 2021

We consider a SEAIR epidemic model with Atangana–Baleanu fractional-order derivative. We approximate the solution of the model using the numerical scheme developed by Toufic and Atangana. The numerical simulation corresponding to several fractional orders shows that, as the fractional order reduces from 1, the spread of the endemic grows slower. Optimal control analysis and simulation show that the control strategy designed is operative in reducing the number of cases in different compartments. Moreover, simulating the optimal profile revealed that reducing the fractional-order from 1 leads to the need for quick starting of the application of the designed control strategy at the maximum possible level and maintaining it for the majority of the period of the pandemic.
Modeling and analysis of taeniasis and cysticercosis transmission dynamics in humans, pigs and cattle
Authors: Mwasunda Joshua A. , Irunde Jacob I. , Kajunguri Damian , Kuznetsov Dmitry
Published: March 2021

Taeniasis and cysticercosis pose a significant challenge to food safety and public health. Cysticercosis reduces the market value for pigs and cattle by making pork and beef unsafe for consumption. In this paper, a mathematical model for the transmission dynamics of taeniasis and cysticercosis in humans, pigs and cattle is formulated and analyzed. The analysis shows that both the disease free equilibrium (DFE) and the endemic equilibrium (EE) exist. To study the dynamics of the diseases, we derived the basic reproduction number $R_{0}$

R
0

by next generation matrix method. When $R_{0}< 1$

R
0

<
1
, the DFE is globally asymptotically stable whereas when $R_{0} > 1$

R
0

>
1
the EE is globally asymptotically stable. The normalized forward sensitivity index was used to determine sensitive parameters to the diseases. Humans’ recruitment rate, probability of humans’ infection with taeniasis and the defecation rate of taenia eggs by humans with taeniasis are the most positive sensitive parameters to diseases’ transmission whereas the human natural death rate is the most negative sensitive parameter. However, it is biologically unethical and not practical to increase human natural mortality rate for disease control. In this case, other parameters with negative sensitivity indices such as death rate of taenia eggs and proportions of unconsumed infected beef and pork can be considered for disease control. Generally, to control the diseases, more efforts should be made directed to reducing the number of humans who have taeniasis and defecate in the open environment. Also meat inspection and indoor keeping of cattle and pigs should be emphasized.
Appraising psychotherapy case studies in practice-based evidence: introducing Case Study Evaluation-tool (CaSE)
Authors: Kaluzeviciute Greta
Published: March 2021

Systematic case studies are often placed at the low end of evidence-based practice (EBP) due to lack of critical appraisal. This paper seeks to attend to this research gap by introducing a novel Case Study Evaluation-tool (CaSE). First, issues around knowledge generation and validity are assessed in both EBP and practice-based evidence (PBE) paradigms. Although systematic case studies are more aligned with PBE paradigm, the paper argues for a complimentary, third way approach between the two paradigms and their ‘exemplary’ methodologies: case studies and randomised controlled trials (RCTs). Second, the paper argues that all forms of research can produce ‘valid evidence’ but the validity itself needs to be assessed against each specific research method and purpose. Existing appraisal tools for qualitative research (JBI, CASP, ETQS) are shown to have limited relevance for the appraisal of systematic case studies through a comparative tool assessment. Third, the paper develops purpose-oriented evaluation criteria for systematic case studies through CaSE Checklist for Essential Components in Systematic Case Studies and CaSE Purpose-based Evaluative Framework for Systematic Case Studies. The checklist approach aids reviewers in assessing the presence or absence of essential case study components (internal validity). The framework approach aims to assess the effectiveness of each case against its set out research objectives and aims (external validity), based on different systematic case study purposes in psychotherapy. Finally, the paper demonstrates the application of the tool with a case example and notes further research trajectories for the development of CaSE tool.
Antioxidant and antimalarial properties of Sophora exigua Craib. root extract in Plasmodium berghei-infected mice
Authors: Kaewdana Kantarakorn , Chaniad Prapaporn , Jariyapong Pitchanee , Phuwajaroanpong Arisara , Punsawad Chuchard
Published: March 2021

Background

Sophora exiguaCraib. is commonly used in Thailand to reduce fever and increase postpartum breast milk production in women who have hypogalactia. However, there has been no report on the antioxidant and antimalarial properties of this plant. This study aimed to investigate the antioxidant and antimalarial activities ofS. exiguaroot extract and to evaluate its acute toxicity in mice to confirm its safety.

Methods

The in vitro antioxidant activities were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH), superoxide radical, and hydroxyl radical scavenging assays. The in vivo antioxidant activities were determined by detecting the malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the livers of malaria-infected mice. The in vivo antimalarial activity was determined by Peters’ 4-day suppressive test in mice infected withPlasmodium bergheiANKA and orally administeredS. exiguaroot aqueous and ethanolic extracts at different doses (200, 400, and 600 mg/kg body weight). In addition, the acute oral toxicity of the plant extracts was assessed in mice at a dose of 2000 mg/kg body weight.

Results

The ethanolic extract ofS. exiguaroot exhibited inhibition of DPPH radicals, superoxide anions, and hydroxyl radicals, with half maximal inhibitory concentration (IC50) values of 24.63 ± 1.78, 129.78 ± 0.65, and 30.58 ± 1.19 μg/ml, respectively. Similarly, research on the in vivo antioxidant activity indicated that the ethanolic extract ofS. exiguaroot exerted a stronger effect than the aqueous extract. The aqueous extract at doses of 200, 400, and 600 mg/kg had stronger antimalarial activity than the ethanolic extract. The aqueous extract at 600 mg/kg exhibited 60.46% suppression of parasitemia. Increased levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and blood urea nitrogen (BUN) were detected in the mice treated with 2000 mg/kg ethanolic extract, which was related to the results of histopathological analysis of liver tissue, showing ballooning degeneration of hepatocytes, diffuse hepatic hemorrhage, and infiltration of inflammatory cells.

Conclusions

This study demonstrated that the ethanolicS. exiguaroot extract possessed antioxidant properties, and the aqueous extract also had antimalarial activity. Therefore, this plant is an alternative source of new antioxidant and antimalarial agents.
Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study
Authors: Erzin Gamze , Pries Lotta-Katrin , van Os Jim , Fusar-Poli Laura , Delespaul Philippe , Kenis Gunter , Luykx Jurjen J. , Lin Bochao D. , Richards Alexander L. , Akdede Berna , Binbay Tolga , Altınyazar Vesile , Yalınçetin Berna , Gümüş-Akay Güvem , Cihan Burçin , Soygür Haldun , Ulaş Halis , Cankurtaran Eylem Şahin , Kaymak Semra Ulusoy , Mihaljevic Marina M. , Andric-Petrovic Sanja , Mirjanic Tijana , Bernardo Miguel , Mezquida Gisela , Amoretti Silvia , Bobes Julio , Saiz Pilar A. , García-Portilla Maria Paz , Sanjuan Julio , Aguilar Eduardo J. , Santos Jose Luis , Jiménez-López Estela , Arrojo Manuel , Carracedo Angel , López Gonzalo , González-Peñas Javier , Parellada Mara , Maric Nadja P. , Atbaşoğlu Cem , Ucok Alp , Alptekin Köksal , Saka Meram Can ,   Genetic Risk and Outcome of Psychosis (GROUP) investigators, Arango Celso , O’Donovan Micheal C. , Rutten Bart P. F. , Guloksuz Sinan
Published: March 2021

Background

A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls.

Methods

This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate.

Results

ES-SCZ was associated with the GAF dimensions in patients (symptom: B = −1.53, p-value = 0.001; disability: B = −1.44, p-value = 0.001), siblings (symptom: B = −3.07, p-value < 0.001; disability: B = −2.52, p-value < 0.001), and healthy controls (symptom: B = −1.50, p-value < 0.001; disability: B = −1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group.

Conclusions

Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.
Building a Sustainable Comprehensive Multiple Myeloma Program in Western Kenya
Authors: Oduor Mercy A. , Lotodo Teresa C. , Vik Terry A. , Manyega Kelvin M. , Loehrer Patrick , Omondi Austin A. , Oguda John O. , Asirwa Fredrick C.
Published: March 2021

Despite improved treatment strategies for multiple myeloma (MM), patient outcomes in low- and middle-income countries remain poor, unlike high-income countries. Scarcity of specialized human resources and diagnostic, treatment, and survivorship infrastructure are some of the barriers that patients with MM, clinicians, and policymakers have to overcome in the former setting. To improve outcomes of patients with MM in Western Kenya, the Academic Model Providing Access to Healthcare (AMPATH) MM Program was set up in 2012. In this article, the program's activities, challenges, and future plans are described distilling important lessons that can be replicated in similar settings. Through the program, training on diagnosis and treatment of MM was offered to healthcare professionals from 35 peripheral health facilities across Western Kenya in 2018 and 2019. Access to antimyeloma drugs including novel agents was secured, and pharmacovigilance systems were developed. Finally, patients were supported to obtain health insurance in addition to receiving peer support through participation in support group meetings. This article provides an implementation blueprint for similar initiatives aimed at increasing access to care for patients with MM in underserved areas.
Favorable Trisomies and ETV6-RUNX1 Predict Cure in Low-Risk B-Cell Acute Lymphoblastic Leukemia: Results From Children's Oncology Group Trial AALL0331
Authors: Mattano Leonard A. , Devidas Meenakshi , Maloney Kelly W. , Wang Cindy , Friedmann Alison M. , Buckley Patrick , Borowitz Michael J. , Carroll Andrew J. , Gastier-Foster Julie M. , Heerema Nyla A. , Kadan-Lottick Nina S. , Matloub Yousif H. , Marshall David T. , Stork Linda C. , Loh Mignon L. , Raetz Elizabeth A. , Wood Brent L. , Hunger Stephen P. , Carroll William L. , Winick Naomi J.
Published: March 2021

PURPOSE

Children's Oncology Group (COG) AALL0331 tested whether pegaspargase intensification on a low-intensity chemotherapy backbone would improve the continuous complete remission (CCR) rate in a low-risk subset of children with standard-risk B-acute lymphoblastic leukemia (ALL).

METHODS

AALL0331 enrolled 5,377 patients with National Cancer Institute standard-risk B-ALL (age 1-9 years, WBC < 50,000/μL) between 2005 and 2010. Following a common three-drug induction, a cohort of 1,857 eligible patients participated in the low-risk ALL random assignment. Low-risk criteria included no extramedullary disease, < 5% marrow blasts by day 15, end-induction marrow minimal residual disease < 0.1%, and favorable cytogenetics ( ETV6-RUNX1 fusion or simultaneous trisomies of chromosomes 4, 10, and 17). Random assignment was to standard COG low-intensity therapy (including two pegaspargase doses, one each during induction and delayed intensification) with or without four additional pegaspargase doses at 3-week intervals during consolidation and interim maintenance. The study was powered to detect a 4% improvement in 6-year CCR rate from 92% to 96%.

RESULTS

The 6-year CCR and overall survival (OS) rates for the entire low-risk cohort were 94.7% ± 0.6% and 98.7% ± 0.3%, respectively. The CCR rates were similar between arms (intensified pegaspargase 95.3% ± 0.8% v standard 94.0% ± 0.8%; P = .13) with no difference in OS (98.1% ± 0.5% v 99.2% ± 0.3%; P = .99). Compared to a subset of standard-risk study patients given identical therapy who had the same early response characteristics but did not have favorable or unfavorable cytogenetics, outcomes were significantly superior for low-risk patients (CCR hazard ratio 1.95; P = .0004; OS hazard ratio 5.42; P < .0001).

CONCLUSION

Standard COG therapy without intensified pegaspargase, which can easily be given as an outpatient with limited toxicity, cures nearly all children with B-ALL identified as low-risk by clinical, early response, and favorable cytogenetic criteria.
Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial
Authors: Cobleigh Melody A. , Anderson Stewart J. , Siziopikou Kalliopi P. , Arthur Douglas W. , Rabinovitch Rachel , Julian Thomas B. , Parda David S. , Seaward Samantha A. , Carter Dennis L. , Lyons Janice A. , Dillmon Melissa S. , Magrinat Gustav C. , Kavadi Vivek S. , Zibelli Allison M. , Tiriveedhi Lavanya , Hill Matthew L. , Melnik Marianne K. , Beriwal Sushil , Mamounas Eleftherios P. , Wolmark Norman
Published: March 2021

PURPOSE

Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS).

PATIENTS AND METHODS

Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years.

RESULTS

There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years.

CONCLUSION

Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.
Glofitamab, a Novel, Bivalent CD20-Targeting T-Cell–Engaging Bispecific Antibody, Induces Durable Complete Remissions in Relapsed or Refractory B-Cell Lymphoma: A Phase I Trial
Authors: Hutchings Martin , Morschhauser Franck , Iacoboni Gloria , Carlo-Stella Carmelo , Offner Fritz C. , Sureda Anna , Salles Gilles , Martínez-Lopez Joaquín , Crump Michael , Thomas Denise N. , Morcos Peter N. , Ferlini Cristiano , Bröske Ann-Marie E. , Belousov Anton , Bacac Marina , Dimier Natalie , Carlile David J. , Lundberg Linda , Perez-Callejo David , Umaña Pablo , Moore Tom , Weisser Martin , Dickinson Michael J.
Published: March 2021

PURPOSE

Glofitamab is a T-cell–engaging bispecific antibody possessing a novel 2:1 structure with bivalency for CD20 on B cells and monovalency for CD3 on T cells. This phase I study evaluated glofitamab in relapsed or refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL). Data for single-agent glofitamab, with obinutuzumab pretreatment ( Gpt) to reduce toxicity, are presented.

METHODS

Seven days before the first dose of glofitamab (0.005-30 mg), all patients received 1,000 mg Gpt. Dose-escalation steps were determined using a Bayesian continuous reassessment method with overdose control. Primary end points were safety, pharmacokinetics, and the maximum tolerated dose of glofitamab.

RESULTS

Following initial single-patient cohorts, 171 patients were treated within conventional multipatient cohorts and received at least one dose of glofitamab. This trial included heavily pretreated patients with R/R B-NHL; most were refractory to prior therapy (155; 90.6%) and had received a median of three prior therapies. One hundred and twenty-seven patients (74.3%) had diffuse large B-cell lymphoma, transformed follicular lymphoma, or other aggressive histology, and the remainder had indolent lymphoma subtypes. Five (2.9%) patients withdrew from treatment because of adverse events. Cytokine release syndrome occurred in 86 of 171 (50.3%) patients (grade 3 or 4: 3.5%); two (1.2%) patients experienced grade 3, transient immune effector cell–associated neurotoxicity syndrome-like symptoms. The overall response rate was 53.8% (complete response [CR], 36.8%) among all doses and 65.7% (CR, 57.1%) in those dosed at the recommended phase II dose. Of 63 patients with CR, 53 (84.1%) have ongoing CR with a maximum of 27.4 months observation.

CONCLUSION

In patients with predominantly refractory, aggressive B-NHL, glofitamab showed favorable activity with frequent and durable CRs and a predictable and manageable safety profile.
Study of Abelian dominance in Sp(N) QCD in the de Sitter background
Authors: Raval Haresh
Published: March 2021

We propose the effective theory based on the compact symplectic group Sp(N) in the new quadratic gauge on the 4-dimensional de Sitter spacetime (dS
4) with a view to investigate the infrared regime in it. Abelian dominance is characterized by off-diagonal gluons acquiring dynamical masses and it hints at existence of confinement. We do observe Abelian dominance in the ghost condensed vacuum of this theory in the de Sitter background. Along with this observation, we find an unusual result that the mass of an off-diagonal gluon on dS
4 is position dependent as a consequence of the curved geometry. In our previous papers, we have shown that Abelian dominance is strongly indicated in the Minkowski spacetime too. Therefore, the present observation suggests that the curvature of the dS
4 does not change the infrared behaviour of the present theory on dS
4 from that of the quadratic gauge fixed theory in Minkowski spacetime, but it causes the mass of an off-diagonal gluon on the dS
4 to be position dependent.
Revisiting the Role of Insulin-like Growth Factor-1 Measurement After Surgical Treatment of Acromegaly
Authors: Jung In-Ho , Choi Seonah , Ku Cheol Ryong , Lee Sang-Guk , Lee Eun Jig , Kim Sun Ho , Kim Eui Hyun
Published: March 2021

Context

In the management of growth hormone (GH)–secreting pituitary adenomas, the oral glucose tolerance test (OGTT) has been the gold standard not only for diagnoses but also for the determination of biochemical remission. Insulin-like growth factor-1 (IGF-1) is an essential biomarker, although it should be adjusted for both age and sex.

Objective

We evaluated whether IGF-1 levels could serve as a reliable alternative to an OGTT for disease monitoring after the surgical treatment of acromegaly. We retrospectively reviewed the medical records of 320 patients who underwent surgical resection of their GH-secreting pituitary tumors at the Severance hospital. Receiver operator characteristic (ROC) analyses were performed to validate the accuracy of IGF-1 levels for the assessment of remission. In addition, regression analyses were performed to identify factors associated with discrepancy between OGTT and IGF-1 levels.

Results

Except for 1 week after surgery, ROC analyses showed an area under the curve of greater than 0.8 for IGF-1 at all time points. Of 320 patients, 270 achieved endocrine remission after surgery alone. Among these patients, IGF-1 levels were normalized in 250 patients. The mean duration from surgery to IGF-1 normalization was 4.7 months. Regression analyses demonstrated that risk of failed IGF-1 normalization was increased by 3.1-fold when the tumor invaded the cavernous sinus and increased by 9.0-fold in patients with incomplete tumor removal.

Conclusion

IGF-1 level is a reliable alternative to OGTT and plays a valuable role in monitoring acromegaly status.
Diabetes Knowledge and Metabolic Control in Type 1 Diabetes Starting With Continuous Glucose Monitoring: FUTURE-PEAK
Authors: Broos Ben , Charleer Sara , Bolsens Nancy , Moyson Carolien , Mathieu Chantal , Gillard Pieter , De Block Christophe
Published: March 2021

Purpose

To investigate whether diabetes knowledge and health literacy impact glycemic control after 1 year of intermittently scanned continuous glucose monitoring (isCGM) in people with type 1 diabetes  ≥ 16 years.

Methods

In this prospective real-world cohort study, we assessed diabetes knowledge using a new 10-item questionnaire [Patient Education and Knowledge (PEAK)] and health literacy using the validated 6-item Newest-Vital Sign-D (NVS-D) questionnaire. Primary endpoint was association between PEAK score and change in hemoglobin A1c (HbA1c). Secondary endpoints were link between NVS-D score and change in HbA1c and that between time spent in/above/below range and PEAK/NVS-D scores.

Results

851 subjects were consecutively recruited between July 2016 and July 2018. Median PEAK score was 8 (range: 0-10), and median NVS-D score was 6 (range 0-6). HbA1c evolved from 7.9% (7.8%-8.0%), 63 (62-64) mmol/mol, at start to 7.7% (7.6%-7.7%), 61 (60-61) mmol/mol (P < 0.001), at 6 months and to 7.8% (7.7%-7.9%), 62 (61-63) mmol/mol, at 12 months (P < 0.001). HbA1c only improved in subgroups with higher scores [PEAK subgroups with score 7-8 (P = 0.005) and 9-10 (P < 0.001) and NVS-D score 4-6 (P < 0.001)]. At 12 months, time spent below 70 mg/dL was reduced by 15% (P < 0.001), and time spent below 54 mg/dL was reduced by 14% (P < 0.001), irrespective of PEAK/NVS-D score. Multiple linear regression analysis demonstrated an association of PEAK score, scan frequency, and baseline HbA1c with evolutions in time in range and time in hyperglycemia.

Conclusions

isCGM reduced time in hypoglycemia, and HbA1c evolved favorably. Our findings suggest that diabetes and health literacy affect glucometrics, emphasizing the importance of education.
Complete Endotracheal Tube Transection by Patient Bite: A Case Report and Algorithm for Fragment Identification and Extraction
Authors: Ilg Annette , Eikermann Matthias , Synn Andrew J.
Published: March 2021

We describe a case of a complete endotracheal tube (ETT) transection due to patient bite. The patient was intubated for postoperative pneumonia; during weaning of sedation, the patient was unable to tolerate pressure support ventilation (PSV) due to agitation. Adaptive support ventilation (ASV) improved patient comfort substantially. During a routine Spontaneous Breathing Trial (SBT) on PSV, the patient bit through the ETT, resulting in complete transection and an unsecured 20-cm airway fragment. Utilizing a multidisciplinary approach, we provided respiratory support and performed nasopharyngolaryngoscopy (NPL) to identify and extract the foreign body. An algorithm for management of ETT fragment extraction is provided.
Introduction
Authors: Hirschkind Charles
Published: March 2021

In the lead essay to this special section, Talal Asad explores some of the avenues opened up by Wittgenstein's work for students of religion. Highlighting some of the philosopher's key insights on the life of language, Asad argues that, instead of taking the opposition between belief and practice as a starting point, scholars should attend to the variety of ways language comes to be used in contexts of embodied learning, contexts wherein the abilities and aptitudes germane to religious life are developed and honed. Turning his focus to what Wittgenstein called the “grammar” of such key concepts as conviction, persuasion, and critique, Asad points to some of the ways that our secular understandings of these notions are inadequate for grasping their place within religious lives. In the latter part of the essay, Asad brings a Wittgensteinian perspective to bear on a key debate within the Islamic tradition concerning the “rationality” of divine speech. The article is followed by five commentaries that take up and expand on different themes found in Asad's essay and developed elsewhere in his work.
Palestinians inside Israel
Authors: Kayyal Majd , Safi Lubna
Published: March 2021

The Palestinian student movement inside the Israeli academy was established within hostile universities. Palestinian students were not engaged in any institutional production of knowledge and therefore could not develop an alternative, anti-colonial framework within the Israeli academy. These conditions made the national student movement into a mirror of the traditional political parties in Israel, marked by the uncritical adoption of the traditional parties' positions. The student movement was administered by party power at all levels and was denied any organizational or intellectual autonomy. The parties remained dominant over student politics, and we have not seen any radical breaks with them. This strong tie has weakened the potential for a revolutionary, anti-Zionist approach within the Palestinian student movement and has resulted in its gradual collapse.
Not Paradise but Prison
Authors: Tod Pinjra
Published: March 2021

In the fall of 2019, Pinjra Tod (Break the Cage), an autonomous collective of women students working to ensure secure, affordable, and non-discriminatory accommodation for women students throughout Delhi, joined forces with other student organizations to coordinate a joint protest and public meeting against the continuing siege of Kashmir. The action took place at the Arts Faculty of Delhi University. In this pamphlet, Pinjra Tod interrogates Narendra Modi's corporate plans for a “paradise” in Kashmir under the capitalist guise of “freedom,” and its intersection with far-right racialized nationalism. Further, they report on the horrific stories emerging from Kashmir: stories of the detention and torture of minors and young men, arbitrary midnight raids, and constant threats and danger of sexual violence against women by the armed forces. They articulate the present state of emergency as an intensification of the long and brutal history of oppression by the Indian state impacting the lives and democratic aspirations of the people of Kashmir. Raising their voices against the continuing lockdown and in support of and solidarity with the people of Kashmir, Pinjra Tod presents a set of demands which include that Articles 370 and 35A of India's constitution be reinstated; that the popular participation of Kashmiri people in any further policy decision be ensured; that all political leaders, social activists, youth, and children be released; and that special provisions be made for all Kashmiri students across all universities whose studies were disrupted.
Excerpt from The Official Anti-Milo Toolkit
Authors: Hofmann-Kuroda Lisa , De Martelly Beezer , Havard Julia , Armstrong-Price Amanda , Kunkel Juliet , Cowan Sarah
Published: March 2021

The organizers of the Anti-Milo Toolkit aimed to contribute to a broader counter-movement that would make it easier for university campuses to challenge and de-platform white supremacist and fascist speakers sheltered under the auspices of “free speech.” This toolkit gathers info-tracts, syllabi, flyer templates, and other activist materials collected and widely distributed across campuses in preparation to protest Breitbart journalist Milo Yiannopoulos's 2016 “Dangerous Faggot Tour.” Yiannopoulos was slated to speak at thirteen college campuses in support of an alt-right platform founded upon the weaponization of “free speech,” xenophobia, and transphobia. In addition to providing materials for protest, the authors of the “Anti-Milo Toolkit” take critical aim at appropriation of liberal-academic vocabularies by right-wing groups and Yiannopoulos's history of outing trans and undocumented students at his events, and call for widespread action against the spread of violent rhetoric targeting marginalized communities in order to maintain the university as a space of sanctuary. Because of its accessibility via digital channels and its wide range of short and readable pieces written in a variety of styles, and because of the collective's wide network of organizing connections, the kit circulated very broadly.
The alx3 gene shapes the zebrafish neurocranium by regulating frontonasal neural crest cell differentiation timing
Authors: Mitchell Jennyfer M. , Sucharov Juliana , Pulvino Anthony T. , Brooks Elliott P. , Gillen Austin E. , Nichols James T.
Published: March 2021

During craniofacial development, different populations of cartilage- and bone-forming cells develop in precise locations in the head. Most of these cells are derived from pluripotent cranial neural crest cells and differentiate with distinct developmental timing and cellular morphologies. The mechanisms that divide neural crest cells into discrete populations are not fully understood. Here, we use single-cell RNA sequencing to transcriptomically define different populations of cranial neural crest cells. We discovered that the gene family encoding the Alx transcription factors is enriched in the frontonasal population of neural crest cells. Genetic mutant analyses indicate that alx3 functions to regulate the distinct differentiation timing and cellular morphologies among frontonasal neural crest cell subpopulations. This study furthers our understanding of how genes controlling developmental timing shape craniofacial skeletal elements.
Polish adaptation of emotional Stroop test in assessment of pedophilia – a pilot study
Authors: Oronowicz-Jaśkowiak Wojciech , Lew-Starowicz Michał
Published: March 2021

Cel pracy

Przeprowadzono badanie pilotażowe celem stworzenia polskiej adaptacji zadania Stroopa do oceny preferencji pedofilnych.

Metoda

Badanie składało się z dwóch etapów obejmujących stworzenie materiału testowego poprzez uszeregowanie odpowiednich list słów przez sędziów kompetentnych. Drugi etap badania polegał na weryfikacji empirycznej założeń zadania Stroopa w warunku emocjonalnym wśród populacji nieklinicznej.

Wyniki

Na podstawie oceny pięciu sędziów kompetentnych dokonano uszeregowania słów od najbardziej do najmniej pobudzających seksualnie (W Kendalla od 0.368 do 0.693). Otrzymano sześć uszeregowanych list, poproszono ponownie sędziów kompetentnych o ocenę czy stworzone listy słów będą właściwe dla badania (współczynnik trafności Lawshe'a CVR od 0.6 do 1.0). Połączono dwie kategorie słów. Otrzymano pięć uszeregowanych list, poproszono ponownie sędziów kompetentnych o ocenę czy stworzone listy słów będą właściwe dla badania (współczynnik trafności Lawshe'a CVR 1.0). Stworzona lista słów uzyskała ostatecznie akceptację wszystkich sędziów kompetentnych.
Na podstawie badań eksperymentalnych przeprowadzonych na osobach z populacji nieklinicznej, wykazano, zgodnie z założeniami konstrukcyjnymi narzędzia, że średni czas reakcji na słowa o charakterze seksualnym jest dłuższy w porównaniu do słów neutralnych. Średni czas reakcji na słowa dziecięce nie różnił się istotnie od słów neutralnych.

Wnioski

Na podstawie badań z udziałem sędziów kompetentnych oraz przeprowadzonych badań empirycznych, stworzono wstępną polską adaptację zadania Stroopa w warunku emocjonalnym do diagnozy preferencji pedofilnych. W celu wykorzystania zadania w praktyce klinicznej, konieczne są dalsze badania z udziałem osób z preferencjami pedofilnymi.
El humor verbal frente a los procedimientos de face-work
Authors: Szeflińska-Baran Magdalena , Baran Marek
Published: March 2021

El objetivo del estudio es analizar algunas peculiaridades del humor verbal desde la perspectiva del llamado face-work (Brown y Levinson, 1978, 1987). El concepto de posicionamiento interaccional remite a determinados cuestionamientos acerca de la relación que se establece entre las prácticas humorísticas y la (re)configuración del territorio interpersonal. Por consiguiente, trataremos de averiguar en qué medida las manifestaciones del humor verbal como bromas o insultos rituales pueden resultar «amenazantes» o «valorizantes» para las imágenes de los interlocutores. Reflexionaremos, de igual modo, sobre los parámetros situacionales y contextuales que pueden poner en peligro el desarrollo de la interacción.
Asset Dissemination Through Dealer Markets
Authors: Colliard Jean-Edouard , Demange Gabrielle
Published: March 2021

In over-the-counter markets for assets, such as bonds and securitizations, large volumes can be split into smaller pieces and gradually sold to several final investors with the intermediation of multiple dealers. This paper proposes a model to study this process, called asset dissemination. A dealer buys several units of an asset from a customer and then sells some units to the dealer’s customers and to a second dealer, who sells to the second dealer’s customers and to a third dealer, and so on. The extent of dissemination is measured by the number of dealers involved and the total customer demand served. We show that asymmetric information on customer demand hinders both dimensions of dissemination. We also study how the quantity to disseminate and the dealers’ funding costs impact dissemination and the prices and quantities in interdealer transactions.

This paper was accepted by Gustavo Manso, finance.
A Finite Time Analysis of Temporal Difference Learning with Linear Function Approximation
Authors: Bhandari Jalaj , Russo Daniel , Singal Raghav
Published: March 2021

Temporal difference learning (TD) is a simple iterative algorithm widely used for policy evaluation in Markov reward processes. Bhandari et al. prove finite time convergence rates for TD learning with linear function approximation. The analysis follows using a key insight that establishes rigorous connections between TD updates and those of online gradient descent. In a model where observations are corrupted by i.i.d. noise, convergence results for TD follow by essentially mirroring the analysis for online gradient descent. Using an information-theoretic technique, the authors also provide results for the case when TD is applied to a single Markovian data stream where the algorithm’s updates can be severely biased. Their analysis seamlessly extends to the study of TD learning with eligibility traces and Q-learning for high-dimensional optimal stopping problems.
Sample Out-of-Sample Inference Based on Wasserstein Distance
Authors: Blanchet Jose , Kang Yang
Published: March 2021

Financial institutions make decisions according to a model of uncertainty. At the same time, regulators often evaluate the risk exposure of these institutions using a model of uncertainty, which is often different from the one used by the institutions. How can one incorporate both views into a single framework? This paper provides such a framework. It quantifies the impact of the misspecification inherent to the financial institution data-driven model via the introduction of an adversarial player. The adversary replaces the institution's generated scenarios by the regulator's scenarios subject to a budget constraint and a cost that measures the distance between the two sets of scenarios (using what in statistics is known as the Wasserstein distance). This paper also harnesses statistical theory to make inference about the size of the estimated error when the sample sizes (both of the institution and the regulator) are large. The framework is explained more broadly in the context of distributionally robust optimization (a class of perfect information games, in which decisions are taken against an adversary that perturbs a baseline distribution).
The implications of Brexit for healthcare in the British Overseas Territories
Authors: Duncan Monica
Published: March 2021

The potential consequences of Brexit for the British Overseas Territories have received little attention in UK government or media. Monica Duncan shines a light on this issue and the UK's responsibilities to these territories.
Study scope
Authors: Menon Shyam , Kuchhai Faiz , Kurien Reuben
Published: March 2021

A brief overview of recently published articles on subjects relevant to endoscopic practitioners
Random pattern hatchet flap as a reconstructive tool in the treatment of pressure sores: clinical experience with 36 patients
Authors: Alfeehan MJ , Aljodah MA-A , Al-Zajrawee MZ , Marzook AA
Published: March 2021

Introduction

Pressure sores represent a reconstructive challenge, and the high recurrence rate and need for reoperations should always be considered. Sacrifice of muscle and fascia in primary reconstruction may compromise options for future repairs. The objective of this study was to evaluate the reliability of muscle- and fascia-sparing random pattern hatchet flap reconstruction of pressure sores in different body regions.

Methods

From November 2017 to December 2019, 36 participants with grade III and IV pressure sores underwent random pattern hatchet flap reconstruction. Early postoperative complications and flap survival were evaluated in follow up for 6–12 months.

Results

Thirty-six participants with an age range of 15 to 67 years who presented with pressure sores (13 sacral, 12 ischial, 10 trochanteric, and 1 scapular) underwent surgery. Complete healing of sores was observed within 21 days of surgery in 32 cases and within 30 days for the remaining four cases. Postoperative complications (11.2%) were recorded in only four participants: two experienced partial wound dehiscence, one seroma developed in a trochanteric case, and there was one infection in a sacral sore.

Conclusions

Random pattern hatchet flap is a reliable tool that results in minimal complications for treatment of pressure sores of limited dimensions.
Analysis of surface changes from undermining and building site categorization: The case study in mining location Louky near Karvina
Authors: Dolezalova Hana
Published: March 2021

Repeated geodetic observations were applied in mining location Louky near Karviná to detect surface changes from undermining in complex geo-mechanical conditions. Analyses of the subsidence magnitude and the length and direction of horizontal displacements showed that the subsidence trough was formed unevenly not only due to the position of the exploited local longwall panels and their different size but also showed a notable effect of the dominant tectonic fault. The significantly uneven development of the subsidence trough negatively affects line constructions. Terrain deformations of the road and stream pipeline were computed and classified into the building site categories according to the Czech standard ČSN 73 0039. The course of individual deformations in the monitored locality is influenced by a complex geo-mechanical situation. While the course of the subsidence curves is continuous at the observed pipeline and the classification of individual sections into building site categories corresponds with that, the road profile points out a more complex development of surface deformations. At the end of the observed period, 5 % of the profiles’ sections fell into category III (medium intensity), 49 % into category IV (moderate intensity) and 32 % stayed in category V (very moderate intensity of mining effects).