bluuebunny/crossref_metadata_2025 huggingface dataset:
Resumption of anti‐programmed cell death 1 monotherapy for severe immune‐related adverse events experienced patient with renal cell carcinoma
Authors: Maegawa Yoko , Kato Taigo , Fukuhara Shinichiro , Kiuchi Hiroshi , Imamura Ryoichi , Uemura Motohide , Nonomura Norio , Fujita Kazutoshi
Published: June 2020

Introduction

Combined anti‐cytotoxic‐T‐lymphocyte antigen 4 and programmed cell death 1 blockade induced high rates of immune‐related adverse events in patients with renal cell carcinoma. However, the safety of reinitiating anti‐programmed cell death 1 monotherapy for patients who discontinued combination therapy due to immune‐related adverse events is largely unknown.

Case presentation

We report the case of 74‐year‐old man who received combination therapy with anti‐cytotoxic‐T‐lymphocyte antigen 4 and programmed cell death 1 inhibitors for advanced renal cell carcinoma. After three cycles of combination therapy, he complained severe immune‐related adverse events including grade 3 nausea and anorexia, and grade 3 diarrhea, leading to discontinuation of the therapy. He started readministration of anti‐programmed cell death 1 monotherapy at 41 weeks after discontinuation due to the new lung metastatic lesion. Importantly, he experienced only grade 1 diarrhea, which can be controlled with prednisolone.

Conclusion

The readministration of anti‐programmed cell death 1 monotherapy with close monitoring can be an acceptable treatment even after discontinuation of combination therapy.
Developmental patterns of emotion regulation in toddlerhood: Examining predictors of change and long‐term resilience
Authors: Noroña‐Zhou Amanda N. , Tung Irene
Published: June 2020

Emotion regulation is critical for optimal functioning across a wide range of domains and may be even more important for individuals in high‐risk environments. While evidence suggests that childhood is generally a period of emotion regulation growth and development, research is needed to examine factors that may contribute to deviations from a typical trajectory. In a prospective study of 1,905 children, latent class growth analysis (LCGA) was used to identify trajectory groups of emotion regulation across toddlerhood (age 14–36 months), examine predictors of those trajectory groups from child temperament, parenting behaviors, and environmental risk, and explore predictions of resilience in 5th grade from the identified groups. LGCA supported a three‐class model, with a Stable Incline group, a Decline group, and a Catch‐Up group. Child negative emotionality, positive and negative parenting, and environmental risk predicted group membership. These trajectory groups in toddlerhood were predictive of child resilient functioning in the 5th grade. Our findings highlight the importance of utilizing developmental models of emotion regulation and provide implications for prevention and early intervention services to enhance emotion regulation development in early childhood.
Selective anticancer activity of superparamagnetic iron oxide nanoparticles (SPIONs) against oral tongue cancer using in vitro methods: The key role of oxidative stress on cancerous mitochondria
Authors: Jahanbani Jahanfar , Ghotbi Maryam , Shahsavari Fatemeh , Seydi Enayatollah , Rahimi Shabnam , Pourahmad Jalal
Published: June 2020

Today, it has been proven that the nanoparticles such as superparamagnetic iron oxide nanoparticles (SPIONs) have widespread use in biomedical applications, for instance, in magnetic resonance imaging and targeted delivery of drugs. Despite many studies on SPIONs in diagnosing some diseases like cancer, it has not been investigated on the oral tongue squamous cell carcinoma (OTSCC) detection by the NPs. Hence, the present study has been designed to assess the in vitro cytotoxicity of SPIONs on the isolated mitochondria of OTSCC by mitochondrial tests. Isolated mitochondria were removed from the separated cancer and control tissues from the squamous cells of tango in male Wistar rats (6 or 8 weeks) and exposed to the different concentrations of SPIONs (30, 60, and 120 nM). A rise in the production of reactive oxygen species is one of the significant mechanisms of this study, followed by a collapse of mitochondrial membrane potential, the escape of mitochondrial cytochrome c, and mitochondrial swelling in the exposed isolated mitochondria of OTSCC with SPIONs. Furthermore, our results indicated that the exposure to the SPIONs reduced the activity of succinate dehydrogenase in complex II of the mitochondria obtained from cancerous oral tongue squamous. So the SPIONs can induce selective cytotoxicity on the OTSCC mitochondria without significant effects on the control mitochondria. Based on the results and further studies about in vivo experiments in this regard, it is concluded the SPIONs may be a hopeful therapeutic candidate for the treatment of OTSCC.
Therapeutic plasma exchange in acute on chronic liver failure
Authors: Stahl Klaus , Busch Markus , Fuge Jan , Schneider Andrea , Manns Michael P. , Seeliger Benjamin , Schmidt Julius J. , Wiesner Olaf , Schmidt Bernhard M.W. , Taubert Richard , Vondran Florian W.R. , Hoeper Marius M. , David Sascha
Published: June 2020

Background

Acute on chronic liver failure (ACLF) has been identified as a distinct syndrome due to acute decompensation of liver cirrhosis accompanied by extra‐hepatic organ failure, primarily caused by an overwhelming systemic immune response. Therapeutic plasma exchange (TPE) has been demonstrated in a randomized controlled trial to improve transplant free survival in acute liver failure. Here we investigated if TPE might have comparable beneficial effects in patients with ACLF.

Methods

Thirty‐one patients with ACLF that were treated with TPE were enrolled into this retrospective analysis and 1:1 matched to an ACLF cohort treated with standard medical therapy (SMT) only.

Results

Patients considered for a bridge to recovery (n = 21 each group) approach had a 30‐day mortality >90% that was not improved by TPE (P = .185). Deaths occurred in the SMT group at significant earlier time points compared to the patients treated with TPE (mortality at 5 days: 33.3% for TPE and 66.7% for SMT, P = .048). However, patients who received TPE as a bridge to transplant strategy (n = 10) survived in 60% of cases and demonstrated 24 hours after study inclusion a stabilization of organ dysfunction (organ failures at inclusion: 4 (3‐5) vs 24 hours after inclusion: 3 (2‐4), P = .031 and CLIF‐C‐ACLF score: 64 (49‐76) vs 54 (49‐66), P = .043) not seen in SMT patients.

Conclusions

Although these retrospective data need to be interpreted with caution, they suggest that TPE in ACLF patients is feasible but not suitable as a bridge to recovery strategy. In selected patients TPE might assist as bridge to transplant.
The clinical value of lncRNA MALAT1 and its targets miR‐125b, miR‐133, miR‐146a, and miR‐203 for predicting disease progression in chronic obstructive pulmonary disease patients
Authors: Liu Shuang , Liu Min , Dong Lixia
Published: June 2020

Objective

The study aimed to explore the correlations of long non‐coding RNA MALAT1 (lncRNA MALAT1) and its targets microRNA (miR)‐125b, miR‐133, miR‐146a, and miR‐203 with acute exacerbation risk, inflammation, and disease severity of chronic obstructive pulmonary disease (COPD).

Methods

Plasma samples were obtained from 120 acute exacerbation COPD (AECOPD) patients, 120 stable COPD patients, and 120 healthy controls (HCs). RT‐qPCR was conducted to detect lncRNA MALAT1 expression and its target miRNAs, and ELISA was performed to detect the inflammatory cytokines.

Results

LncRNA MALAT1 was highest in AECOPD patients followed by stable COPD patients and then HCs, which distinguished AECOPD patients from HCs (AUC: 0.969, 95% CI: 0.951‐0.987) and stable COPD patients (AUC: 0.846, 95% CI: 0.798‐0.894). Furthermore, lncRNA MALAT1 positively correlated with GOLD stage in both AECOPD and stable COPD patients. Regarding inflammatory cytokines, lncRNA MALAT1 positively correlated with tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, IL‐6, IL‐8, IL‐17, and IL‐23 in both AECOPD and stable COPD patients. Besides, lncRNA MALAT1 negatively correlated with miR‐125b, miR‐146a, and miR‐203 in AECOPD patients and reversely correlated with miR‐125b and miR‐146a in stable COPD patients. Notably, miR‐125b, miR‐133, miR‐146a, and miR‐203 were the lowest in AECOPD patients, followed by stable COPD patients, and then HCs; miR‐125b, miR‐133, miR‐146a, and miR‐203 negatively correlated with inflammation and GOLD stage in AECOPD and stable COPD patients.

Conclusion

LncRNA MALAT1 exhibits clinical implications in acute exacerbation risk prediction and management of COPD via the inner‐correlation with its targets miR‐125b, miR‐146a, and miR‐203.
Film, psychotherapy, and the taming of rage at the mother
Authors: Knafo Danielle
Published: June 2020

In this essay, I show how difficult emotions, like aggression and murderous rage, are grappled with in horror movies. Patients' reactions to viewing these films can take place in a safe, creative, therapeutic space that allows for even the darkest themes. I discuss three patients who related to intense rage at the mother when viewing the films Joker and Jurassic Park. One patient watched Jurassic Park 50 times and shared his thoughts about the significance this film, and films in general, held for him throughout his life. It is theorized that when patients bring films into the clinical arena, they create a third space that exists between therapist and patient, a safe transitional space within which to explore difficult and otherwise unacceptable feelings.
Relationship between FGF21 and drug or nondrug therapy of type 2 diabetes mellitus
Authors: Guo Chang , Zhao Li , Li Yanyan , Deng Xia , Yuan Guoyue
Published: June 2020

Sedentary and high‐calorie diets are associated with increased risk of obesity and type 2 diabetes mellitus, while exercise and diet control are also important nondrug treatments for diabetes. Fibroblast growth factor 21 (FGF21) is an important cytokine, which is mainly expressed in liver, fat and muscle tissue responding to nutrition and exercise, and plays an important role in the improvement of glucose and lipid metabolism. Due to the increasing serum FGF21 level in obesity and diabetes, FGF21 can be used as a predictor or biomarker of diabetes. A variety of clinical antidiabetic drugs can reduce the content of FGF21, possibly for the improvement of FGF21 sensitivity. In this paper, we reviewed the interactions between FGF21 and nondrug therapy (diet and exercise) for diabetes and explored the potential value of the combined application of clinical antidiabetic drugs and FGF21.
Nicotinic acid adenine dinucleotide phosphate activates two‐pore channel TPC1 to mediate lysosomal Ca2+ release in endothelial colony‐forming cells
Authors: Moccia Francesco , Zuccolo Estella , Di Nezza Francesca , Pellavio Giorgia , Faris Pawan S. , Negri Sharon , De Luca Antonio , Laforenza Umberto , Ambrosone Luigi , Rosti Vittorio , Guerra Germano
Published: June 2020

Nicotinic acid adenine dinucleotide phosphate (NAADP) is the most recently discovered Ca2+‐releasing messenger that increases the intracellular Ca2+ concentration by mobilizing the lysosomal Ca2+ store through two‐pore channels 1 (TPC1) and 2 (TPC2). NAADP‐induced lysosomal Ca2+ release regulates multiple endothelial functions, including nitric oxide release and proliferation. A sizeable acidic Ca2+ pool endowed with TPC1 is also present in human endothelial colony‐forming cells (ECFCs), which represent the only known truly endothelial precursors. Herein, we sought to explore the role of the lysosomal Ca2+ store and TPC1 in circulating ECFCs by harnessing Ca2+ imaging and molecular biology techniques. The lysosomotropic agent, Gly–Phe β‐naphthylamide, and nigericin, which dissipates the proton gradient which drives Ca2+ sequestration by acidic organelles, caused endogenous Ca2+ release in the presence of a replete inositol‐1,4,5‐trisphosphate (InsP3)‐sensitive endoplasmic reticulum (ER) Ca2+ pool. Likewise, the amount of ER releasable Ca2+ was reduced by disrupting lysosomal Ca2+ content. Liposomal delivery of NAADP induced a transient Ca2+ signal that was abolished by disrupting the lysosomal Ca2+ store and by pharmacological and genetic blockade of TPC1. Pharmacological manipulation revealed that NAADP‐induced Ca2+ release also required ER‐embedded InsP3 receptors. Finally, NAADP‐induced lysosomal Ca2+ release was found to trigger vascular endothelial growth factor‐induced intracellular Ca2+ oscillations and proliferation, while it did not contribute to adenosine‐5′‐trisphosphate‐induced Ca2+ signaling. These findings demonstrated that NAADP‐induced TPC1‐mediated Ca2+ release can selectively be recruited to induce the Ca2+ response to specific cues in circulating ECFCs.
Bcl‐2‐associated athanogene 5 overexpression attenuates catecholamine‐induced vascular endothelial cell apoptosis
Authors: Zhu Hang , Zhao Maoxiang , Chen Yundai , Li Dandan
Published: June 2020

Bcl‐2 associated athanogene 5 (Bag5) is a novel endoplasmic reticulum (ER) regulator. However, its role in catecholamine‐induced endothelial cells damage has not been fully understood. In our study, catecholamine was used to mimic hypertension‐related endothelial cell damage. Then, western blots, enzyme‐linked immunosorbent assay, immunofluorescence, quantitative polymerase chain reaction and pathway analysis were conducted to analyze the role of Bag5 in endothelial cell damage in response to catecholamine. Our results indicated that the endothelial cell viability was impaired by catecholamine. Interestingly, Bag5 overexpression significantly reversed endothelial cell viability. Mechanistically, Bag5 overexpression inhibited ER stress, attenuated oxidative stress and repressed inflammation in catecholamine‐treated endothelial cells. These beneficial effects finally contributed to endothelial cell survival under catecholamine treatment. Pathway analysis demonstrated that Bag5 was under the control of the mitogen‐activated protein kinase (MAPK)–extracellular‐signal‐regulated kinase (ERK) signaling pathway. Reactivation of the MAPK–ERK pathway could upregulate Bag5 expression and thus promote endothelial cell survival through inhibiting oxidative stress, ER stress, and inflammation. Altogether, our results illustrate that Bag5 overexpression sustains endothelial cell survival in response to catecholamine treatment. This finding identifies Bag5 downregulation and the inactivated MAPK–ERK pathway as potential mechanisms underlying catecholamine‐induced endothelial cell damage.
An ankle sprain with long‐term swelling and pain successfully treated with the traditional Japanese herbal medicine Jidabokuippo: A case report
Authors: Yoshinaga Ryo , Nakayasu Kazuo , Tahara Eiichi
Published: June 2020

In this report, we present a case in which long‐term swelling and pain because of an ankle sprain were successfully treated with the traditional Japanese herbal (Kampo) medicine Jidabokuippo. Jidabokuippo was created in Japan and has been used to treat swelling and pain associated with trauma. A 44‐year‐old woman sprained her right ankle and received the standard treatments including icing and immobilization for three weeks. However, the swelling, redness, and pain of her ankle continued for two months after the treatments. After initiating Jidabokuippo, her pain and swelling were promptly improved. This suggests that Jidabokuippo is a potentially promising pharmacotherapy for patients with ankle sprain which has not recovered smoothly. It is said that Jidabokuippo can be prescribed simply referring to pain and swelling of the affected areas; therefore, it should be considered as a treatment for trauma patients with long‐term swelling and pain.
Carbon‐metalated triazines and tetrazines: Synthesis and reactivity
Authors: Ivanov Sergey M.
Published: June 2020

The current review is focused on the routes for the synthesis, chemical properties and reactivity of sp2‐ and sp3‐carbon‐metalated triazines and tetrazines. The reported experimental data for the known compounds and intermediates including the alkali, alkaline earth, transition, and other groups 1 to 14 metal and metalloid derivatives of triazines and tetrazines were systematized. Electrophile trapping, transmetalation, couplings as well as ring opening and rearrangement reactions and their applications for the synthesis of functionalized molecules were considered.
Multisystem inflammatory syndrome in children related to COVID‐19: A New York City experience
Authors: Riollano‐Cruz Mariawy , Akkoyun Esra , Briceno‐Brito Eudys , Kowalsky Shanna , Reed James , Posada Roberto , Sordillo Emilia Mia , Tosi Michael , Trachtman Rebecca , Paniz‐Mondolfi Alberto
Published: June 2020

In December 2019, the 2019, a novel coronavirus disease (COVID‐19) caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) first emerged in Wuhan, China. This has now spread worldwide and was declared a pandemic by March 2020. Initially, the pediatric population was described as a low risk for severe COVID‐19. However, reports have emerged recently of cases of COVID‐19 in children with a systemic inflammatory disease, with features that overlap with Kawasaki disease (KD). We describe the first 15 cases with the multi‐systeminflammatory syndrome in children (MIS‐C), temporally related to COVID‐19, who presented for care to a tertiary pediatric referral center in New York City. We discuss the disproportionate burden of disease among Hispanic/Latino and Black/African American ancestry, the distinct cytokine signature across the disease spectrum (IL‐1/IL‐6), and the potential role and pathogenesis of SARS‐CoV‐2 in this new clinical entity.
Quantifying Response to Nutrition Therapy During Critical Illness: Implications for Clinical Practice and Research? A Narrative Review
Authors: Fetterplace Kate , Ridley Emma J. , Beach Lisa , Abdelhamid Yasmine Ali , Presneill Jeffrey J. , MacIsaac Christopher M. , Deane Adam M.
Published: June 2020

Critical illness causes substantial muscle loss that adversely impacts recovery and health‐related quality of life. Treatments are therefore needed that reduce mortality and/or improve the quality of survivorship. The purpose of this Review is to describe both patient‐centered and surrogate outcomes that quantify responses to nutrition therapy in critically ill patients. The use of these outcomes in randomized clinical trials will be described and the strengths and limitations of these outcomes detailed. Outcomes used to quantify the response of nutrition therapy must have a plausible mechanistic relationship to nutrition therapy and either be an accepted measure for the quality of survivorship or highly likely to lead to improvements in survivorship. This Review identified that previous trials have utilized diverse outcomes. The variety of outcomes observed is probably due to a lack of consensus as to the most appropriate surrogate outcomes to quantify response to nutrition therapy during research or clinical practice. Recent studies have used, with some success, measures of muscle mass to evaluate and monitor nutrition interventions administered to critically ill patients.
Implementation Patterns of Two Evidence‐Based Psychotherapies in Veterans Affairs Residential Posttraumatic Stress Disorder Programs: A Five‐Point Longitudinal National Investigation
Authors: Cook Joan M. , Simiola Vanessa , Thompson Richard , Mackintosh Margaret‐Anne , Rosen Craig , Sayer Nina , Schnurr Paula P.
Published: June 2020

The present study examined the patterns of adoption of two evidence‐based psychotherapies (EBPs)—prolonged exposure (PE) and cognitive processing therapy (CPT)—in U.S. Department of Veterans Affairs (VA) residential posttraumatic stress disorder (PTSD) treatment programs. A total of 526 providers from 39 programs nationwide completed online quantitative surveys and qualitative interviews, collected at five assessment points between 2008 and 2015, concerning the use of PE and CPT. By the midpoint of the study period, responders from most programs reported having adopted one or both EBPs as either core components of their programs or “tracks” for certain patients within their programs, adoption rates were 52.8% of programs at Time 3, 61.0% at Time 4, and 66.7% at Time 5. Evaluation of adoption patterns over time suggested that CPT was used in more programs and with more patients within programs compared to PE. At Time 5, respondents from half of the programs reported little or no adoption of PE, whereas the CPT adoption rate was reported to be “little or none” for one‐fifth of the programs. The adoption of PE was generally slower compared to CPT adoption. The slower rate of adoption may be related to the resource‐intensive nature of implementing PE on an individual basis in a residential setting as compared to the multiple ways CPT can be delivered: individually or in group settings, and with or without the inclusion of the trauma narrative. Strategies to improve sustainability measurement and implications for implementation science are discussed.
Adding Flexible Instrumentation to a Curved Videolaryngoscope: A Novel Tool for Laryngeal Surgery
Authors: Schild Leon R. , Böhm Felix , Boos Marco , Kahrs Lüder A. , Coburger Jan , Greve Jens , Dürselen Lutz , Hoffmann Thomas K. , Schuler Patrick J.
Published: June 2020

Objectives

Transoral surgery of the larynx with rigid instruments is not always possible. This may result in insufficient therapy or in an increased need for open surgery. For these patients, alternative surgical systems are needed. Here, we demonstrate a curved prototype for laryngeal surgery equipped with flexible instruments.

Study Design

Pre‐clinical user study in an ex vivo porcine laryngeal model.

Methods

The prototype was built from established medical devices, namely a hyperangulated videolaryngoscope and modified flexible instruments as well as three‐dimensional printed parts. Feasibility of laryngeal manipulation was evaluated in a user study (n = 19) with a porcine ex vivo laryngeal model. Using three different visualization technologies, the participants performed various fine motor skills tasks and rated the usability of the system on a 5‐point Likert scale.

Results

Exposure, accessibility, and manipulation of important laryngeal structures were always possible using the new prototype. The participants needed considerably less time (mean, 96.4 seconds ± 6.4 seconds vs. 111.5 seconds ± 4.5 seconds, P = .18), reported significantly better general impression (mean score 3.0 vs. 3.8, P = .041) and significantly lower user head and neck strain (2.6 vs. 1.7, P = .022) using a 40‐inch television screen as compared to a standard videolaryngoscope monitor.

Conclusion

The results indicate that our curved prototype and large monitor visualization may provide a cost‐effective minimally invasive alternative for difficult laryngeal exposure. Its special advantages include avoiding the need for a straight line of sight and a simple and cost‐effective construction. The system could be further improved through advances in camera chip technology and smaller instruments. Laryngoscope, 131:E561–E568, 2021
Family Planning in Liver Transplant: Patient and Provider Knowledge and Practices
Authors: Ritchie Julia , Seidman Dominika , Srisengfa Yanin , Perito Emily R. , Sarkar Monika
Published: June 2020

Fertility is often impaired in adolescents and women with cirrhosis, but it is rapidly restored after liver transplantation (LT). Early and unplanned pregnancies confer increased risks to maternal, fetal, and graft health, underscoring the need for reproductive counseling. However, data on reproductive practices or counseling in the LT setting are limited. An anonymous online Qualtrics (Provo, UT) survey was sent to transplant patients and providers to gauge knowledge and practices surrounding contraception and pregnancy. Eligible participants included transplant patients aged 14‐45 years and their transplant providers. Patient response was 50.0% (74/148), 14 of whom were pre‐LT patients and 60 of whom were post‐LT patients. Counseling occurred in 37% of patients prior to transplant and 82% after transplant. Most patients (86%) considered family planning a high priority in their transplant care. Contraception‐ and pregnancy‐specific counseling was provided by LT providers in 60% and 44% of patients, respectively. The most desired mode of counseling by patients was in‐person discussion with an LT provider (89%). Despite most post‐LT patients receiving counseling, only 41% used contraception during the first year after LT, of whom 32% relied on high failure methods. Of the 31/43 (72.1%) provider responses, 96% voiced interest in additional reproductive education. Most providers (90%) correctly advised that patients delay pregnancy during the first year after LT, although misconceptions about safety of estrogen and intrauterine devices were selected by 53% and 42%, respectively. Some favored resources by providers were educational pamphlets in clinic (88%) and automated note templates to prompt family planning inquiry (72%). Transplant patients and providers have key deficiencies in their knowledge of contraception and corresponding practices. Most post‐LT patients receive counseling, yet contraception practices are inadequate for preventing unplanned pregnancy. Discussion with transplant providers was the most favored counseling modality by patients, underscoring our critical role in optimizing post‐LT reproductive care.
In Situ‐Forming Glucose‐Responsive Hydrogel from Hyaluronic Acid Modified with a Boronic Acid Derivative
Authors: Holz Emily , Rajagopal Karthikan
Published: June 2020

Hydrogels are a promising class of biomaterials for sustained drug release applications. The use of covalently cross‐linked hydrogels for drug delivery applications may be limited due to their manufacturing complexity and the high injection forces required for their administration. Stimulus‐responsive hydrogels, which are engineered to respond to stimuli such as pH, temperature, ionic strength, or chemical potential, may overcome these shortcomings and enable the development of injectable hydrogels. This study presents a strategy for forming hydrogels such that a sol–gel transition occurs in response to physiologically relevant glucose concentrations. A hyaluronic acid (HA) polymer backbone is modified with 3‐aminophenylboronic acid, which is able to reversibly bind glucose with a 2:1 stoichiometry. The boronic acid‐functionalized polymer is demonstrated to be glucose responsive, as indicated by its spontaneous hydrogelation and subsequent increase in stiffness as a function of glucose concentration. Furthermore, the transient nature of the boronic acid‐glucose cross‐linking enables the hydrogel to self‐heal after physical rupture. A proof‐of‐concept gelation in alkaline conditions is demonstrated, but the system may be adapted for gelation at physiological pH using modified boronic acids. These HA–boronic acid conjugates have potential utility as in situ‐forming hydrogels for sustained drug release applications.
Monochorionic diamniotic twins of discordant external genitalia with 45,X/46,XY mosaicism
Authors: Takahashi Ken , Sato Taisuke , Nishiyama Miyuki , Sasaki Aiko , Taniguchi Kosuke , Migita Ohsuke , Wada Seiji , Hata Kenichiro , Sago Haruhiko
Published: June 2020

Background

Monozygotic twins with 45,X/46,XY mosaicism, discordant for phenotypic sex, are extremely rare.

Methods

This report describes the clinical findings of a rare case of 45,X/46,XY mosaicism in monozygotic twins with different external genitalia. Single nucleotide polymorphism (SNP) array analysis, performed by collecting DNA from each umbilical cord, showed identical SNPs in the autosomal chromosomes of both fetuses.

Results

Chorionic villus sampling of a 37‐year‐old primigravida carrying monozygotic twins revealed a 45,X/46,XY karyotype. Autopsy of the aborted fetuses revealed a penis and testes on one fetus and a vagina, uterus, and ovaries in the other fetus––which also had severe cystic hygroma. Cell counting using fluorescence in situ hybridization with XY probes (XY‐FISH) showed 20% and 80% abundance of 45,X cells in the internal genitalia, liver, heart, lung, adrenal gland, bone marrow, and spine of the male and female fetuses, respectively.

Conclusion

These results indicated that the fetuses were genetically monozygotic twins and their different degrees of mosaicism may have resulted in different genital phenotypes.
Modeling natural convective heat transfer within an inclined enclosure in the presence of copper oxide/water nanofluid
Authors: Yan Shu‐Rong , Kalbasi Rasool , Toghraie Davood , Tian Xiao‐Xiao , Nguyen Quyen , Karimipour Arash
Published: June 2020

In this study, the effects of adding CuO nanoparticles (NPs) on natural convection heat transfer within an enclosure by considering Brownian motions and thermophoresis were discussed. For this purpose, copper oxide NPs were inserted to water at 1, 3, and 5 vol.%. Using two‐phase model, at constant Grashof (104) and Richardson numbers (102), the enclosure angularity efficacy on the heat transfer was examined at 30°, 45°, and 60°. Adding NPs has one positive effect (thermal conductivity enhancement) and one negative point (viscosity augmentation). It was found that up to 1 vol.%, the addition of NPs improves (due to the superiority of the positive effect on the negative effect) the thermal conductivity but upon 1%, the negative effect is preferred to the positive effect, and hence heat transfer is diminished. At Ri = 100, only adding 1% of the NPs enhanced the Nusselt number (Nu) and adding more NPs diminished the Nu. The angle of the enclosure affects the concentration distribution of the NPs and diminishes eases the NP homogeneity as well. As the enclosure angle augmented from 30° to 60°, the Nu improved by 47%. Note that at the best conditions, adding NPs improved the Nu up to 2%.
Characterization of Weyl operator in terms of Mehler–Fock transform
Authors: Verma Sandeep Kumar , Prasad Akhilesh
Published: June 2020

In this paper, we define the windowed‐Mehler–Fock transform and introduce the corresponding Weyl transform. Further, we examine the boundedness of windowed‐Mehler–Fock transform in Lebesgue space and establish some of its fundamental properties. Also, we give the criteria of boundedness and compactness of Weyl transform in Lebesgue space.
Boundedness in a three‐dimensional two‐species and two‐stimuli chemotaxis system with chemical signalling loop
Authors: Pan Xu , Wang Liangchen , Zhang Jing
Published: June 2020

The following two‐species chemotaxis system with a chemical signalling loop under Lotka–Volterra competitive kinetics

is considered in a bounded domain
with homogeneous Neumann boundary conditions, and the parameters μi,ai>0 (i=1,2) and χj>0(j=1,2,3), the initial data are nonnegative and satisfy
. Global boundedness solution of this system is proved under the conditions

and
Flip bifurcations of two systems of difference equations
Authors: Cheng Qi , Deng Shengfu
Published: June 2020

This paper investigates the bifurcations of the following difference equations

where a,b,c, and d are positive constants and the initial conditions x0 and y0 are positive numbers. Psarros, Papaschinopoulos, and Schinas (Math. Methods Appl. Sci., 2016, 39: 5216–5222) presented the semistability of the fixed point (0,0) when one eigenvalue is equal to 1 and the other eigenvalue has absolute value less than 1. In this paper, we consider another case: one eigenvalue is equal to −1. With the aid of the center manifold reduction theorem, we rigorously show that these two systems undergo flip bifurcations or generalized flip bifurcations. Moreover, the stability of the fixed point (0,0) and the existence of period‐two cycles are also given.
A structurally damped σ‐evolution equation with nonlinear memory
Authors: D'Abbicco Marcello , Girardi Giovanni
Published: June 2020

In this paper, we investigate the global (in time) existence of small data solutions to the Cauchy problem for the following structurally damped σ‐evolution model with nonlinear memory term:

with σ>0. In particular, for γ∈((n−σ)/n,1), we find the sharp critical exponent, under the assumption of small data in L1. Dropping the L1 smallness assumption of initial data, we show how the critical exponent is consequently modified for the problem. In particular, we obtain a new interplay between the fractional order of integration 1−γ in the nonlinear memory term and the assumption that initial data are small in Lm, for some m>1.
Scavenger Receptor Class B Type I is Required for 25‐Hydroxycholecalciferol Cellular Uptake and Signaling in Myeloid Cells
Authors: Tenesaca Shirley , Vasquez Marcos , Fernandez‐Sendin Myriam , Di Trani Claudia Augusta , Ardaiz Nuria , Gomar Celia , Cuculescu Doina , Alvarez Maite , Otano Itziar , Melero Ignacio , Berraondo Pedro
Published: June 2020

Scope

Vitamin D3 is a critical molecule for the properly controlled activity of the immune system. In myeloid‐derived cells, vitamin D3 induces the production of the antimicrobial and antitumor peptide cathelicidin. In this study, the mechanism of the entry of 25‐hydroxycholecalciferol (25(OH)D) in myeloid‐derived cells is explored.

Methods and results

Here, a novel regulatory pathway of vitamin D3 biology is described. Using a polyclonal antibody, two different chemical inhibitors, and a high‐density lipoprotein as a competing ligand, it is demonstrated here that the 25(OH)D signaling pathway in myeloid cells depends on scavenger receptor class B type I (SR‐B1). This effect is observed in the THP‐1 monocytic cell line and in human primary monocytes. SR‐B1 blockade abrogates the cellular uptake of 25(OH)D leading to a general shut down of the gene transcription program modulated by 25(OH)D. The results obtained at the transcriptional level are confirmed at the protein and functional level for CD14 in the THP‐1 cell line.

Conclusion

In conclusion, SR‐B1 plays a critical role in vitamin D3 biology, paving the way for novel therapeutic interventions.
CL‐MIPv6: A cross‐layer approach for fast‐internetwork‐mobility support in 6LoWPAN wireless sensor networks
Authors: Hamidi‐Alaoui Zakaria , Moussa Noureddine , El Belrhiti El Alaoui Abdelbaki
Published: June 2020

Considered as part of the Internet of Things (IoT) concept, Internet‐connected wireless sensor networks (WSNs) are increasingly using sensor nodes with mobility option. The mobility of sensor nodes is not necessarily limited within a single WSN but could also be across several WSNs. From this, efficiency, flexibility, and interoperability with the existing infrastructure are mandatory features. Unfortunately, current mobility management solutions are not optimized sufficiently for WSNs. In this paper, we propose a new solution (named as CL‐MIPv6) that uses detected link‐layer information with an adapted scheme of the standard MIPv6 to provide constrained mobile nodes with fast, reliable, and low‐cost internetwork handoffs. The idea behind our proposal consists of enabling reliable internetwork mobility anticipation, fast foreign‐network detection, and then processing low‐overhead handoff‐related signaling at mobile nodes. The evaluation of the proposed solution has demonstrated remarkable improvements in terms of reliability and energy‐latency costs of internetwork handoffs. The advantage of the contribution over its counterparts becomes more significant as the mobility speed and the overall network traffic load increase.
Routing electric vehicles with a single recharge per route
Authors: Löffler Maximilian , Desaulniers Guy , Irnich Stefan , Schneider Michael
Published: June 2020

Driven by environmental considerations, regulations on vehicle emissions, and the offer of major subsidies, electric commercial vehicles (ECVs) are receiving ever stronger attention in logistics companies. Route planning for ECV fleets requires consideration of the special characteristics of ECVs, like limited driving range and the potential need to recharge en route at dedicated recharging stations. From a practical viewpoint, the number of recharge operations of each vehicle can very often be restricted to one recharge per route because (i) typical route distances in the most important application areas of ECVs, like small package shipping and food or beverage distribution, do not require more than one recharge given the current driving range of ECVs, and (ii) operations managers are very reluctant to plan vehicle routes with two or more recharges because recharging operations are perceived as unproductive idle times. We develop a simple hybrid of large neighborhood search and granular tabu search to solve the resulting electric vehicle‐routing problem with time windows and single recharge (EVRPTWS), considering the possibility of both full and partial recharge. The heuristic works on routes represented as customer sequences, and recharge operations are implicitly considered by determining the recharging position in the route, the recharging station to visit, and the amount to be recharged in optimal fashion. We discuss how our algorithm can be extended to handle nonlinear recharging times, different recharging times per station, and time‐dependent waiting times at stations. In numerical studies on EVRPTWS instances from the literature, the method provides optimal or near‐optimal solutions for instances with up to 100 customers within reasonable runtimes. Additional studies investigate the cost savings potential of partial recharges in comparison to full recharges in the presence of time‐window constraints, and examine the factors that influence this cost saving potential.
Financial access, governance and the persistence of inequality in Africa: Mechanisms and policy instruments
Authors: Tchamyou Vanessa S.
Published: June 2020

The aim of this paper is to investigate policy instruments by which the persistence of inequality is affected by financial development channels in 48 African countries for the period of 1996–2014. Financial dynamic channels of depth, efficiency, activity and stability are used. Political, economic and institutional governance policy instruments are also involved. The empirical evidence is based on the generalised method of moments. The results show that financial depth and financial stability are the best channels of reducing inequality. Moreover, the relevance of these financial channels is significantly apparent when policy instruments are exclusively governance variables. The comparative relevance of governance dynamics in the persistence of inequality is discussed. The study responds to two recent policy and scholarly challenges, notably: the persistence of inequality in Africa and the relevance of governance in addressing income inequality by means of financial access.
Meta‐analysis of the risk of autoimmune thyroiditis, Guillain‐Barré syndrome, and inflammatory bowel disease following vaccination with AS04‐adjuvanted human papillomavirus 16/18 vaccine
Authors: Rosillon Dominique , Willame Corinne , Tavares Da Silva Fernanda , Guignard Adrienne , Caterina Sophie , Welby Sarah , Struyf Frank
Published: June 2020

Purpose

To assess the risk of three autoimmune diseases ‐ autoimmune thyroiditis (AIT), Guillain‐Barré syndrome (GBS), and inflammatory bowel disease (IBD) ‐ in females following AS04‐HPV‐16/18 vaccination.

Methods

This meta‐analysis included data from 18 randomized controlled trials, one cluster‐randomized trial, two large observational retrospective cohort studies, and one case‐control study. Following vaccination, a risk window of 2 years was defined for AIT and IBD and 42 days for GBS. Odds ratios (ORs) were estimated using three methods: meta‐analysis inverse‐variance with continuity correction (primary analysis), pooled estimate, and beta‐binomial regression.

Results

In all studies apart from the case‐control study, 154 398 exposed and 1 504 322 non‐exposed subjects were included, among whom there were 141 and 1972 cases of (autoimmune) thyroiditis; 2 and 2 cases of GBS; and 43 and 401 cases of IBD, respectively. In the case‐control study, there were 97 cases of AIT and 13 of GBS; matched with 802 and 130 controls, respectively. The primary analysis OR estimates were 1.46 (95% confidence interval [CI] 1.22‐1.76), 11.14 (2.00‐61.92), and 1.11 (0.75‐1.66) for (autoimmune) thyroiditis, GBS, and IBD, respectively.

Conclusions

This meta‐analysis did not show an increased risk of IBD following vaccination with AS04‐HPV‐16/18. The 1.5‐fold increased risk of (autoimmune) thyroiditis does not allow us to conclude about a causal association. For GBS, the very low number of cases and wide 95% CIs negate any firm conclusion.
Clinical evaluation of cochlear implantation in children younger than 12 months of age
Authors: Yang Yang , Chen Min , Zheng Jun , Hao Jinsheng , Liu Bing , Liu Wei , Li Bei , Shao Jianbo , Liu Haihong , Ni Xin , Zhang Jie
Published: June 2020

Importance

Cochlear implantation (CI) is an effective therapy for patients with severe to profound sensorineural hearing loss. It remains controversial whether children younger than 12 months of age should undergo CI.

Objective

To evaluate the safety and effectiveness of CI in children younger than 12 months of age.

Methods

We performed a retrospective study of clinical data of pediatric patients younger than 12 months of age who underwent CI and were followed up for 1 to 2 years. Patients’ developmental levels were evaluated by the Gesell score before CI. Intraoperative and postoperative complications were recorded to evaluate the safety of CI. Auditory and speech abilities were scored by the LittlEARS® auditory questionnaire (LEAQ), categories of auditory performance (CAP), speech intelligibility rating (SIR), infant‐toddler meaningful auditory integration scale (IT‐MAIS), and meaningful use of speech scale (MUSS) at 1, 2, 3, 6, 9, and 12 months after CI. The associations between clinical characteristics before CI and postoperative scores at 1 year after CI were analyzed by the linear mixed‐effects model.

Results

Eighty‐nine children (47 boys and 42 girls) were included in this study (mean age at CI, 9.2 ± 1.6 months). Sixteen patients were diagnosed with cochlear malformation and 16 underwent bilateral CI. No severe complications occurred in any patients. The mean developmental quotient of the Gesell score was 78.00 ± 10.03. The median LEAQ scores were 0, 5, 10, 16, 22, 26 and 30 before and at 1, 2, 3, 6, 9, and 12 months after CI, respectively. These findings implied that the LEAQ score greatly improved in the first year after CI. The overall CAP, SIR, IT‐MAIS, and MUSS scores also increased with increasing duration after CI. No significant associations were detected between clinical characteristics (age, sex, implant number, pre‐CI Gesell score, and inner ear malformation) and LEAQ outcomes at 12 months after CI.

Interpretation

With increasing duration after CI, auditory and speech behavior dramatically improve in young children. Our findings indicate that CI is feasible for children younger than 12 months of age.
Characterization of T‐DM1‐resistant breast cancer cells
Authors: Sauveur Juliette , Conilh Louise , Beaumel Sabine , Chettab Kamel , Jordheim Lars‐Petter , Matera Eva‐Laure , Dumontet Charles
Published: June 2020

The development of targeted therapies has drastically improved the outcome of patients with different types of cancer. T‐DM1 (trastuzumab‐emtansine) is an antibody‐drug conjugate used for the treatment of HER2‐positive breast cancer combining the FDA approved mAb (monoclonal antibody) trastuzumab and the microtubule cytotoxic agent DM1 (emtansine). Despite clinical successes achieved by targeted therapies, a large number of patients develop resistance during treatment. To explore mechanisms of resistance to T‐DM1, the MDA‐MB‐361 HER2‐positive breast cancer cell line was exposed in vitro to T‐DM1 in the absence or presence of ciclosporin A. Previously reported mechanisms of resistance such as trastuzumab‐binding alterations, MDR1 upregulation, and SLC46A3 downregulation were not observed in these models. Despite a decrease in HER2 expression at the cell surface, both resistant cell lines remained sensitive to HER2 targeted therapies such as mAbs and tyrosine kinase inhibitors. In addition, sensitivity to DNA damaging agents and topoisomerase inhibitors were unchanged. Conversely resistance to anti‐tubulin agents increased. Resistant cells displayed a decreased content of polymerized tubulin and a decreased content of βIII tubulin although the downregulation of βIII tubulin by siRNA in the parental cell line did not modified the sensitivity to T‐DM1. Both cell lines resistant to T‐DM1 also presented giant aneuploid cells. Several SLC (solute carrier) transporters were found to be differentially expressed in the resistant cells in comparison to parental cells. These results suggest that some characteristics such as increased baseline aneuploidy and altered intracellular drug trafficking might be involved in resistance to T‐DM1.
Low‐energy Sr2MSbO5.5 (M = Ca and Sr) structures show significant distortions near oxygen vacancies
Authors: Patel Megha , Zhong Jiayun , Gomez‐Haibach Konrad S. , Gomez Maria A. , King Graham
Published: June 2020

Inspired by significant local distortions found near vacancies in a neutron pair distribution function analysis study (G. King et al., Inorg. Chem. 2012, 51, 13060) of Sr2MSbO5.5 (M = Ca and Sr), this computational study finds minimum‐energy structures with these and related distortions using density functional theory (DFT) with the Perdew‐Burke‐Ernzerhof (PBE) functional as implemented in the Vienna Ab Initio Simulations Package (VASP) (G. Kresse and J. Furthmüller, Phys. Rev. B, 1996, 54, 11169; G. Kresse and J. Hafner, Phys. Rev. B, 1993, 47, 558; G. Kresse and J. Furthmüller, Comput. Mater. Sci., 1996, 6, 15). All structures were optimized using the conjugate gradient method. The global minima found for both systems featured trigonal bipyramid SbO5 structures and edge sharing with M‐centered polyhedra. However, while calcium ions occupied full and partial octahedra, the larger strontium ions were more commonly found in full and partial pentagonal bipyramids. Molecular dynamics with velocity rescaling at 1200 K revealed movements of the oxygen vacancy via polyhedral rotations. This work highlights the need to consider both square pyramid to trigonal bipyramid rearrangements around small ions and rotational polyhedral movements in simulating oxygen vacancy conduction in oxygen‐deficient double perovskites.
Successful treatment of telomeropathy‐related interstitial lung disease with immunosuppression and danazol
Authors: Chambers Daniel C. , Lutzky Viviana P. , Apte Simon H. , Godbolt David , Feenstra John , Mackintosh John
Published: June 2020

We report the case of a 42‐year‐old female with a history of finger clubbing which improved during pregnancy, a history of unexplained hepatosplenomegaly, and subsequent non‐specific interstitial pneumonia with respiratory failure. Given a personal and family history of early greying of the hair, the peripheral blood monocyte telomere length was measured and was confirmed to be <1st centile, explaining the multiorgan presentation. She was treated with prednisolone, mycophenolate mofetil, and the synthetic androgen danazol with a dramatic improvement in respiratory failure and lung function. After 18 months of danazol treatment, the peripheral blood monocyte telomere length had returned to the normal range.