bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted Protein Degradation as a Promising Tool for Epigenetic Upregulation of Fetal Hemoglobin
Authors: J. Verheul Thijs C. , Trinh Van Tuan , Vázquez Olalla , Philipsen Sjaak
Published: October 2020

The level of fetal hemoglobin (HbF) is an important disease modifier for β‐thalassemia and sickle cell disease patients. Indeed, genetic tinkering with the HbF repression machinery has demonstrated great potential for disease mitigation. Such genetic treatments are costly and the high incidence of β‐hemoglobinopathies in low‐income countries, therefore, calls for the development of affordable, off‐the‐shelf, oral treatments. The use of PROTAC (PRoteolysis TArgeting Chimeras) technology to influence the epigenetic mechanisms involved in HbF suppression may provide a solution. In this minireview, we briefly explain the HbF repression network highlighting the epigenetic factors that could be targeted for degradation by PROTACs. We hope that this review will inspire clinicians, molecular and chemical biologists to collaborate and contribute to this fascinating field, which should ultimately deliver drugs that reactivate HbF expression with high specificity and low toxicity.
Patient and diagnostic intervals of survivors of sarcoma: Results from the SURVSARC study
Authors: Soomers Vicky L. M. N. , Husson Olga , Desar Ingrid M. E. , van de Sande Michiel A. J. , de Haan Jacco J. , Verhoef Cornelis , Vriens Ingeborg J. H. , van Houdt Winan J. , van de Poll‐Franse Lonneke , van der Graaf Winette T. A.
Published: October 2020

Background

Patients diagnosed with sarcoma are hypothesized to experience a prolonged route to a cancer diagnosis. This route, the total interval, can be divided into a patient interval (the time from the appearance of symptoms to physician consultation) and diagnostic interval (time from the first consultation to diagnosis). In the current study, the authors investigated these intervals among survivors of sarcoma and identified factors associated with prolonged intervals.

Methods

A cross‐sectional study was conducted among adult patients with sarcoma 2 to 10 years after diagnosis. Patients completed a questionnaire regarding their total interval, which was linked to clinical data from the Netherlands Cancer Registry. Descriptive statistics were used to describe intervals. Based on Dutch clinical guidelines, a diagnostic interval ≥1 month was considered to be prolonged and an interval ≥3 months was considered as very long. Multivariable regression analyses investigated associations between patient and tumor characteristics and interval length.

Results

A total of 1099 participants were included (response rate, 58%); approximately 60% reported a patient interval ≥1 month and 36% reported a patient interval ≥3 months. Risk factors for a very long patient interval were sarcoma of the skin or pelvis, liposarcoma, or rhabdomyosarcoma. Stage III disease was associated with a shorter patient interval. The diagnostic interval length was ≥1 month in 55% of patients and ≥3 months in 28% of patients. Risk factors for a very long diagnostic interval were female sex, age <70 years, or having a synovial sarcoma or chordoma.

Conclusions

The patient and diagnostic interval lengths were prolonged in a substantial percentage of this sarcoma survivorship population. Factors found to be associated with the length of the patient interval or the diagnostic interval differed. Creating awareness among (especially young) patients to consult a physician and awareness among physicians to consider a sarcoma diagnosis will contribute to optimization of the total interval.
Immunosuppression and cardiovascular dysfunction in patients with severe versus mild coronavirus disease 2019: a case series
Authors: Bao Hejing , Li Gang , Fang Yinhua , Lai Qin , Bao Hehong , Zheng Yu , Hu Yanjun
Published: October 2020

Objectives

As coronavirus disease 2019 (COVID‐19) continues to spread globally, we aimed to describe and compare changes in the immune and cardiovascular systems of patients with mild versus severe COVID‐19 at different time points during the course of disease.

Methods

One hundred and one patients diagnosed with COVID‐19 who underwent serial peripheral blood collection and chest computed tomography (CT) imaging were enrolled in this study and grouped by the severity of their illness. Changes in the immune and cardiovascular systems were analysed and compared between groups.

Results

The study included 43 women and 58 men, with a median age of 45 years (interquartile range [IQR], 16–71). We identified spleen shrinkage in 27.7% of study patients. Ratios of spleen volume to patient (skin) volume were compared, with evidence that severe patients had more splenic shrinkage than mild patients. Lymphopenia was observed in 65.3% of patients, and 27.3% of patients had persistently low levels of lymphocytes after discharge. Tachycardia occurred mainly during the first 2 days of hospitalisation, with increases in creatine kinase–myocardial band levels in 10 (9.9%) patients and arrhythmias in 16 (15.8%) patients.

Conclusions

In addition to pulmonary manifestations, our study demonstrated that other organ systems can also be affected during COVID‐19 infection, with evidence of immunosuppression and cardiovascular dysfunction, which may contribute to increased mortality rates in critically ill COVID‐19 patients.
The distribution of climbing chalk on climbed boulders and its impact on rock‐dwelling fern and moss species
Authors: Hepenstrick Daniel , Bergamini Ariel , Holderegger Rolf
Published: October 2020

Rock climbing is popular, and the number of climbers rises worldwide. Numerous studies on the impact of climbing on rock‐dwelling plants have reported negative effects, which were mainly attributed to mechanical disturbances such as trampling and removal of soil and vegetation. However, climbers also use climbing chalk (magnesium carbonate hydroxide) whose potential chemical effects on rock‐dwelling species have not been assessed so far. Climbing chalk is expected to alter the pH and nutrient conditions on rocks, which may affect rock‐dwelling organisms. We elucidated two fundamental aspects of climbing chalk. (a) Its distribution along nonoverhanging climbing routes was measured on regularly spaced raster points on gneiss boulders used for bouldering (ropeless climbing at low height). These measurements revealed elevated climbing chalk levels even on 65% of sampling points without any visual traces of climbing chalk. (b) The impact of climbing chalk on rock‐dwelling plants was assessed with four fern and four moss species in an experimental setup in a climate chamber. The experiment showed significant negative, though varied effects of elevated climbing chalk concentrations on the germination and survival of both ferns and mosses. The study thus suggests that along climbing routes, elevated climbing chalk concentration can occur even were no chalk traces are visible and that climbing chalk can have negative impacts on rock‐dwelling organisms.
Predation risk alters life history strategies in an oceanic copepod
Authors: Kvile Kristina Øie , Altin Dag , Thommesen Lotte , Titelman Josefin
Published: October 2020

The ubiquitous oceanic copepod Calanus finmarchicus is the major link between primary producers and important fish stocks in the North Atlantic Ocean and adjacent seas. Despite over a century of research on growth and development of this key species, the effect of predation risk on these processes remains elusive. We tested how food level and chemical cues from a fish predator influence growth and development of C. finmarchicus, using a predator naïve laboratory population. Copepods reached adult stage earlier both in response to high food and to predator cues in our experiment. High food also increased growth and lipid accumulation. In contrast, perceived predation risk triggered reduced size and lipid fullness, indicating a decoupling of growth and development rates. Our results demonstrate that chemical predator cues can influence life history strategies in C. finmarchicus, and suggest that present and future patterns in oceanic zooplankton size and population dynamics may also reflect differences in predation risk.
Human DNA extraction from highly degraded skeletal remains: How to find a suitable method?
Authors: Vinueza‐Espinosa Diana C. , Santos Cristina , Martínez‐Labarga Cristina , Malgosa Assumpció
Published: October 2020

Retrieving DNA from highly degraded human skeletal remains is still a challenge due to low concentration and fragmentation, which makes it difficult to extract and purify. Recent works showed that silica‐based methods allow better DNA recovery and this fact may be attributed to the type of bones and the quality of the preserved tissue. However, more systematic studies are needed to evaluate the efficiency of the different silica‐based extraction methods considering the type of bones. The main goal of the present study is to establish the best extraction method and the type of bone that can maximize the recovery of PCR‐amplifiable DNA and the subsequent retrieval of mitochondrial and nuclear genetic information. Five individuals were selected from an archaeological site located in Catalonia–Spain dating from 5th to 11th centuries AD. For each individual, five samples from different skeletal regions were collected: petrous bone, pulp cavity and cementum of tooth, and rib and limb bones. Four extraction methods were tested, three silica‐based (silica in‐suspension, HE column and XS plasma column) and the classical method based on phenol–chloroform. Silica in‐suspension method from petrous bone and pulp cavity showed the best results. However, the remains preservation will ultimately be the key to the molecular result success.
Deep neural network based anomaly detection in Internet of Things network traffic tracking for the applications of future smart cities
Authors: Reddy Dukka KarunKumar , Behera Himansu Sekhar , Nayak Janmenjoy , Vijayakumar Pandi , Naik Bighnaraj , Singh Pradeep Kumar
Published: October 2020

An anomaly exposure system's foremost objective is to categorize the behavior of the system into normal and untruthful actions. To estimate the possible incidents, the administrators of smart cities have to apply anomaly detection engines to avert data from being jeopardized by errors or attacks. This article aims to propose a novel deep learning‐based framework with a dense random neural network approach for distinguishing and classifying anomaly from normal behaviors based on the type of attack in the Internet of Things. Machine learning algorithms have the improbability to explore the performance, compared with deep learning models. Distinctively, the examination of deep learning neural network architectures achieved enhanced computation performance and deliver desired results for categorical attacks. This article focuses on the complete study of experimentation performance and evaluations on deep learning neural network architecture for the recognition of seven categorical attacks found in the Distributed Smart Space Orchestration System traffic traces data set. The empirical results of the simulation model report that deep neural network architecture performs well through noticeable improvement in most of the categorical attack.
Locally produced personal protective equipment can offer hospital staff protection against Covid‐19 if combined with surgical masks and rigorous personal protective equipment cleaning routine
Authors: Pieterse Pieternella , Dickson Claire , Ndyetabula Lilian , Hardeman Megan , Scanlan Patricia
Published: October 2020

Locally made, washable and reusable personal protective equipment (PPE), used in combination with N95 masks that were reused safely, has proven to be a viable alternative to disposable gowns and caps for hospital staff in low‐ and middle‐income countries. Muhimbili University Hospital's children's cancer ward in Dar es Salaam, Tanzania, developed locally made PPE and created rigorous cleaning and disinfecting protocols, when the daily use of imported, disposable materials were not an option. These items continue to protect staff, children and parents. The novel PPE approach was able to prevent staff from becoming infected during the pandemic despite the fact that several parents, and subsequently their children, became infected with Covid‐19 during cancer treatment at the facility.
Socio‐economic inequality in maternal health care utilization in Sub‐Saharan Africa: Evidence from Togo
Authors: Atake Esso–Hanam
Published: October 2020

Introduction

Despite improvements in health care in Togo, the maternal mortality rate remains high, and regional antenatal care and facility‐based deliveries are limited. The aim of this study is to measure socioe‐conomic inequality in maternal health care (MHC) utilization during pregnancy and delivery.

Method

The data were obtained from the last two rounds of the 1998 and 2013 Togo Demographic and Health Survey. Concentration index, concentration curve and logistic regression were used to measure and examine socio‐economic inequality in antenatal care and facility‐based deliveries.

Results

The concentration indices for antenatal visits and facility‐based deliveries were 0.142 and 0.246 in 1998 and 0.129 and 0.159 in 2013, indicating inequality bias towards the rich in both. Household wealth status and women's education were the most significant contributors to inequality in antenatal visits and facility‐based deliveries. In 2013, household economic status contributed approximately 75.66% of the inequality in facility‐based deliveries, while mothers' education significantly contributed approximately 18.22% to the inequality in antennal visits. Additionally, universal health coverage should be considered as one of the main vehicles for reducing inequalities in the use of MHCs.

Conclusion

The results suggest that inequality in MHC utilization during pregnancy and delivery may be effectively reduced by improving the relevant strategies, in particular, those targeted at reducing poverty and illiteracy. School curricula need to be comprehensively addressed for ensuring essential sexual and reproductive education. Our results suggest that the use of MHC can be increased by broadening health insurance to include exemptions for poor and rural households.
Assessment on estimations of currency basket weights—With coefficient correction for common factor dominance
Authors: Wang Ping , Wang Peijie
Published: October 2020

This paper proposes an approach to correcting parameter misrepresentation under the dominance of a common factor, a customarily overlooked phenomenon. Meanwhile, it provides a general solution to a specific regression bias, namely coefficient correction for common factor dominance in econometrics, which is commonly encountered in the research on currency interactions and co‐movements and beyond. The RMB basket weights are then scrutinized exhaustively, going through all stages of the evolving RMB regime and reforms. Correct and sensible currency basket weights are derived accordingly. It has been found that only the introduction of the central parity regime in 2015 has changed the RMB exchange rate patterns notably. The RMB market behavior and patterns virtually did not change during the prior reforms that had widened the band of daily fluctuation in the RMB exchange rate against the US dollar from 0.3% through to 2%, given the band's unique link to the US dollar.
Therapeutic potential of α,β‐thujone through metabolic reprogramming and caspase‐dependent apoptosis in ovarian cancer cells
Authors: Lee Jin‐Young , Park Hahyun , Lim Whasun , Song Gwonhwa
Published: October 2020

The therapeutic potential of α,β‐thujone, a functional compound found in many medicinal plants of the Cupressaceae, Asteraceae, and Lamiaceae families, has been demonstrated, including in inflammation and cancers. However, its pharmacological functions and mechanisms of action in ovarian cancer remain unclear. We investigated the anticancer properties of α,β‐thujone in ES2 and OV90 human ovarian cancer cells and its effect on sensitization to cisplatin. α,β‐thujone inhibited cancer cell proliferation and induced cell death through caspase‐dependent intrinsic apoptotic pathways. Moreover, α,β‐thujone‐mediated endoplasmic reticulum stress was associated with the loss of mitochondrial functions and altered metabolic landscape of ovarian cancer cells. α,β‐Thujone attenuated blood vessel formation in transgenic zebrafish, implying it has significant antiangiogenic potential. In addition, α,β‐thujone sensitized ovarian cancer cells to cisplatin, causing synergistic pharmacological effects. Collectively, our results suggest that α,β‐thujone has therapeutic potential in human ovarian cancer and functions via regulating multiple intracellular stress‐associated metabolic reprogramming and caspase‐dependent apoptotic pathways.
MOF‐derived nickel−cobalt bimetal oxide nanostructures as a cooperative catalyst for the reduction of 4‐nitrophenol
Authors: Khan Aslam , Wei Dandi , Wang Zhuan , Su Xintai , Wang Jide , Alam Sultan , Wang Lu , Wu Ronglan , Maloletnev Anatoly S , Yang Chao
Published: October 2020

BACKGROUND

4‐Nitrophenol, as a representative hazardous contaminant, may pose potential risks to the environment in the process of production, storage, and use. Catalytic hydrogenation reduction offers a promising route to the removal of 4‐nitrophenol by its transformation into the less toxic and biodegradable 4‐aminophenol. In this work, nickel−cobalt bimetal oxide nanostructures were fabricated by the thermal decomposition of metal organic frameworks and cooperatively utilized for the catalytic reduction of 4‐nitrophenol.

RESULTS

The as‐fabricated oxide catalysts were characterized and analyzed with several physicochemical measurements, including X‐ray diffraction, scanning electron microscopy, transmission electron microscopy, X‐ray photoelectron spectroscopy, thermogravimetry, Fourier‐transform infrared spectroscopy, Raman spectroscopy, nitrogen adsorption, and electrochemical impedance spectroscopy. The catalytic reduction of 4‐nitrophenol was conducted in the presence of the as‐prepared oxide nanostructures with varying Ni/Co ratios to evaluate their catalytic activity. The optimal catalyst (Ni–Co–O) delivered the activity parameter of k’app = 12.0 min−1 mg−1, which was higher than either NiO (2.4 min−1 mg−1) or Co3O4 (3.6 min−1 mg−1). Moreover, the induction time of the 4‐nitrophenol reduction was significantly reduced by using the bimetal oxide catalyst. Based on the surface and electrochemistry analyses, the enhancement of catalytic activity for the Ni–Co bimetal oxide nanostructures was discussed.

CONCLUSION

The above results indicated that the cooperation of nickel with cobalt into bimetal oxide nanostructures exhibited an enhanced catalytic activity, which not only promoted the conversion rate of 4‐nitrophenol, but also shortened the reduction induction period.
Life cycle assessment of wheat production and wheat‐based crop rotations
Authors: Shrestha Prashansa , Karim Rifat A. , Sieverding Heidi L. , Archer David W. , Kumar Sandeep , Nleya Thandi , Graham Christopher J. , Stone James J.
Published: October 2020

In the northern Great Plains (NGP), wheat is the primary grain commodity. There is a need for the NGP to have a detailed analysis of environmental impacts for wheat‐based agricultural production systems to better understand regional agroecosystems. This article provides a cradle‐to‐field gate life cycle assessment (LCA) for NGP dryland wheat (Triticum aestivum L.) production. The environmental impacts for winter wheat production using crop rotation and agricultural intensification are quantified. Fourteen no‐till crop rotations ranging in duration from 2 to 6 yr were evaluated and compared using data from a historical 13‐yr replicated rotation study (>300 observations). Midpoint LCA categories chosen for this comparison are energy, agricultural land use, climate change potential, freshwater eutrophication, and freshwater ecotoxicity due to their direct links with agricultural management practices. The NGP farmers commonly use a fallow period every other year due to moisture limitations. This specific agricultural practice and allocations within rotations are critical considerations within agricultural LCAs. Two aspects of fallow considerations and a sensitivity analysis were also performed. The allocated midpoint impacts between crops in rotational studies averaged 0.31, 0.79, 0.62, and 0.63 kg CO2 eq. per unit of winter wheat when energy, economic, mass, and cereal unit allocations were used, respectively. Economic analysis of the studied experimental crop was performed; results demonstrated that crop insurance policies improved diversification economics by 20%. Agricultural diversification benefits and burdens were better represented by endpoint damage assessments than by midpoint impact analysis.
Contamination characteristics, source analysis, and ecological risk assessment of toxic metals and metalloid in agricultural soil in Yuzhong, China
Authors: Duan Kaixiang , Zhao Baowei , Zhang Songlin , Ma Yanlong
Published: October 2020

Human activities have caused toxic metal pollution and ecological risks to agricultural soil. In this study, 291 topsoil samples, collected in the agricultural soil system of Yuzhong, China, were selected to study the toxic metals and metalloids contamination characteristics, source and ecological risk based on geostatistics, pollution index, and ecological risk index. The main distribution of As is adjacent to pasture land and mainly comes from animal husbandry; Pb was observed near a coal mining factory and the Yellow River and was derived from industry and transportation; Cd was similar to Pb and was mainly derived from industry, transportation, and agriculture; Cr was found near a cement plant and was derived from industry and transportation; and Hg was found near an urban area and was mainly from industry and domestic garbage. The ratio of these elements exceeding the soil background value reached 99.9%. Except for the excess amounts of Cd and Hg in some samples, Cr, Hg, and As were mostly below permissible limits. Moreover, the comprehensive potential ecological risk of toxic metals is mainly at medium level and below, whereas the risks of Cd and Hg are higher. Control of Cd and Hg is important to prevent soil pollution. This study explains the current contamination situation, the predominant contaminants and their sources, and provides emphasis and direction for agricultural soil remediation.
Acute and early HIV infection screening among men who have sex with men, a systematic review and meta‐analysis
Authors: Palmer Shaun , Dijkstra Maartje , Ket Johannes CF , Wahome Elizabeth W , Walimbwa Jeffrey , Gichuru Evanson , van der Elst Elise M , Schim van der Loeff Maarten F , de Bree Godelieve J , Sanders Eduard J
Published: October 2020

Introduction

Screening for acute and early HIV infections (AEHI) among men who have sex with men (MSM) remains uncommon in sub‐Saharan Africa (SSA). Yet, undiagnosed AEHI among MSM and subsequent failure to link to care are important drivers of the HIV epidemic. We conducted a systematic review and meta‐analysis of AEHI yield among MSM mobilized for AEHI testing; and assessed which risk factors and/or symptoms could increase AEHI yield in MSM.

Methods

We systematically searched four databases from their inception through May 2020 for studies reporting strategies of mobilizing MSM for testing and their AEHI yield, or risk and/or symptom scores targeting AEHI screening. AEHI yield was defined as the proportion of AEHI cases among the total number of visits. Study estimates for AEHI yield were pooled using random effects models. Predictive ability of risk and/or symptom scores was expressed as the area under the receiver operator curve (AUC).

Results

Twenty‐two studies were identified and included a variety of mobilization strategies (eight studies) and risk and/or symptom scores (fourteen studies). The overall pooled AEHI yield was 6.3% (95% CI, 2.1 to 12.4; I2 = 94.9%; five studies); yield varied between studies using targeted strategies (11.1%; 95% CI, 5.9 to 17.6; I2 = 83.8%; three studies) versus universal testing (1.6%; 95% CI, 0.8 to 2.4; two studies). The AUC of risk and/or symptom scores ranged from 0.69 to 0.89 in development study samples, and from 0.51 to 0.88 in validation study samples. AUC was the highest for scores including symptoms, such as diarrhoea, fever and fatigue. Key risk score variables were age, number of sexual partners, condomless receptive anal intercourse, sexual intercourse with a person living with HIV, a sexually transmitted infection, and illicit drug use. No studies were identified that assessed AEHI yield among MSM in SSA and risk and/or symptom scores developed among MSM in SSA lacked validation.

Conclusions

Strategies mobilizing MSM for targeted AEHI testing resulted in substantially higher AEHI yields than universal AEHI testing. Targeted AEHI testing may be optimized using risk and/or symptom scores, especially if scores include symptoms. Studies assessing AEHI yield and validation of risk and/or symptom scores among MSM in SSA are urgently needed.
HIV prevalence and incidence in a cohort of South African men and transgender women who have sex with men: the Sibanye Methods for Prevention Packages Programme (MP3) project
Authors: Sullivan Patrick S , Phaswana‐Mafuya Nancy , Baral Stefan D , Valencia Rachel , Zahn Ryan , Dominguez Karen , Yah Clarence S , Jones Jeb , Kgatitswe Lesego B , McNaghten AD , Siegler Aaron J , Sanchez Travis H , Bekker Linda‐Gail
Published: October 2020

Introduction

Men who have sex with men (MSM) and transgender women (TGW) are at increased risk for acquiring HIV, but there are limited HIV incidence data for these key populations in Africa. Understanding HIV prevalence and incidence provides important context for designing HIV prevention strategies, including pre‐exposure prophylaxis (PrEP) programmes. We describe HIV prevalence, awareness of HIV infection, HIV incidence and associated factors for a cohort of MSM and TGW in Cape Town and Port Elizabeth, South Africa.

Methods

From 2015 to 2016, MSM and TGW in Cape Town and Port Elizabeth were enrolled and prospectively followed for 12 months, receiving a comprehensive package of HIV prevention services. HIV testing was conducted at baseline and at follow‐up visits (targeted for three, six and twelve months). All HIV‐negative PrEP‐eligible participants were offered PrEP enrolment during the first four months of study participation. We determined HIV prevalence among participants at baseline, and incidence by repeat screening of initially HIV‐negative participants with HIV tests at three, six and twelve months.

Results

Among 292 participants enrolled, HIV prevalence was high (43%; 95% CI: 38 to 49) and awareness of HIV status was low (50%). The 167 HIV‐negative participants who were followed prospectively for 144.7 person‐years; nine incident HIV infections were documented. Overall annual incidence was 6.2% (CI: 2.8 to 11.8) and did not differ by city. Annual HIV incidence was significantly higher for younger (18 to 19 years) MSM and TGW (MSM: 21.8% (CI: 1.2 to 100); TGW: 31.0 (CI: 3.7, 111.2)). About half of participants started PrEP during the study; the annual incidence of HIV among 82 (49%) PrEP starters was 3.6% (CI: 0.4, 13.1) and among those who did not start PrEP was 7.8% (CI: 3.1, 16.1).

Conclusions

HIV incidence was high among MSM and TGW in the context of receiving a comprehensive package of prevention interventions and offering of PrEP. PrEP uptake was high; the observed incidence of HIV in those who started PrEP was about half the incidence of HIV in those who did not. Future implementation‐oriented studies should focus on decisions to start and continue PrEP for those at highest risk, including young MSM.
Growth factors produced by bone marrow stromal cells on nanoroughened titanium–aluminum–vanadium surfaces program distal MSCs into osteoblasts via BMP2 signaling
Authors: Berger Michael B. , Bosh Kyla B. , Jacobs Thomas W. , Joshua Cohen D. , Schwartz Zvi , Boyan Barbara D.
Published: October 2020

Statement of Clinical Significance: There remains the need to develop materials and surfaces that can increase the rate of implant osseointegration. Though osteoanabolic agents, like bone morphogenetic protein (BMP), can provide signaling for osteogenesis, the appropriate design of implants can also produce an innate cellular response that may reduce or eliminate the need to use additional agents to stimulate bone formation. Studies show that titanium implant surfaces that mimic the physical properties of osteoclast resorption pits regulate cellular responses of bone marrow stromal cells (MSCs) by altering cell morphology, transcriptomes, and local factor production to increase their differentiation into osteoblasts without osteogenic media supplements required for differentiation of MSCs on tissue culture polystyrene (TCPS). The goal of this study was to determine how cells in contact with biomimetic implant surfaces regulate the microenvironment around these surfaces in vitro. Two different approaches were used. First, unidirectional signaling was assessed by treating human MSCs grown on TCPS with conditioned media from MSC cultures grown on Ti6Al4V biomimetic surfaces. In the second set of studies, bidirectional signaling was assessed by coculturing MSCs grown on mesh inserts that were placed into culture wells in which MSCs were grown on the biomimetic Ti6Al4V substrates. The results show that biomimetic Ti6Al4V surface properties induce MSCs to produce factors within 7 days of culture that stimulate MSCs not in contact with the surface to exhibit an osteoblast phenotype via endogenous BMP2 acting in a paracrine signaling manner.
Surgical Management in Tracheobronchopathia Osteochondroplastica: A Case Study
Authors: Dharia Ishaan , Bielamowicz Steven
Published: October 2020

Tracheobronchopathia Osteochondroplastica is a benign condition characterized by osseous and cartilaginous submucosal growths of the tracheobronchial tree. This is a case report of an individual that was to undergo elective surgery using general anesthesia with endotracheal tube intubation. However, the anesthesiologist encountered a large osseous mass of the precricoid region and could not be intubated. This case report describes the technique for removal of the obstructing lesion using a Sonopet ultrasonic aspirator. Laryngoscope, 131:E911–E913, 2021
A New Device for Fine‐Needle Aspiration Cytology Consisting of a Vibrating Linear Resonant Actuator
Authors: Taguchi Atsushi , Kojima Tsuyoshi , Okanoue Yusuke , Kagoshima Hiroki , Hasebe Koki , Yamamoto Hirotaka , Hori Ryusuke
Published: October 2020

Objective

To evaluate the efficacy of a new device for fine‐needle aspiration cytology (FNAC) consisting of a vibrating linear resonant actuator (LRA).

Study Design

Prospective clinical study.

Methods

The LRA frequency was optimized by visualization of the needle motion using a high‐speed camera. The FNAC device consists of a vibrating motor fixed to the stopper of a 5‐ml syringe and piston. Upon insertion of the syringe needle into a thyroid nodule (with the stopper attached to the syringe piston), sufficient negative pressure with 1‐ml suction was maintained. Subsequently, samples were obtained using vibration generated by an LRA or an eccentric rotating mass (ERM). Surgically resected thyroid specimens from 10 patients were evaluated. The number of follicular groups required for adequate diagnosis and the number of larger follicular groups were counted. Next, 254 thyroid nodules from 187 patients were also evaluated by FNAC. The inadequacy rate was determined, and final cytology was classified according to thyroid Bethesda categories.

Results

The optimized LRA frequency was 155 Hz. Both the LRA and ERM devices resulted in sufficient amounts of diagnostic material and achieved low inadequacy rates. The number of large follicular groups obtained was significantly greater with the LRA device compared with the ERM device.

Conclusions

The vibrating device using an LRA for thyroid FNAC resulted in sufficient amounts of thyroid follicular groups and achieved low inadequacy rates. In addition, the LRA device allowed for collection of larger follicular groups sufficient to diagnose appropriate thyroid Bethesda categories.

Level of Evidence

2 Laryngoscope, 131:E1393–E1399, 2021
Barriers to Voice Therapy Attendance in a Language‐Diverse Population
Authors: Lim Kah Whye Ryan , Zambare Wini , Rubin Batsheva R. , Tracy Lauren F.
Published: October 2020

Objectives/Hypothesis

Voice therapy is an effective treatment for many voice disorders, but success depends on attendance and adherence. Many factors hinder treatment attendance, and language discordance with the provider may present an additional obstacle to attending therapy. This study evaluates factors associated with voice therapy attendance at a language‐diverse, safety‐net hospital.

Study Design: Retrospective chart review.

Methods

Retrospective review of adult patients referred to speech language pathology for treatment of voice disorders from January, 2018 to April, 2019. Primary spoken language, interpreter collaboration, and patient demographics were obtained from medical records. Multivariate analysis compared patient factors with voice therapy attendance versus nonattendance.

Results

Of 422 patients, 219 (52%) attended at least one therapy session, whereas 203 (48%) did not attend (n = 120) or schedule therapy (n = 83). In multivariate analysis, only the association between public insurance and nonattendance was statistically significant (P = .016). After adjusting for interpreter use and interval between referral and first appointment, patients with private health insurance were 2.35 times more likely to attend therapy compared to those with public insurance (95% confidence interval: 1.18–4.71). Non‐English language; interpreter collaboration; distance from hospital; and patient demographics, including age, gender, ethnicity, and birthplace, did not significantly correlate with attendance.

Conclusions

In a culturally and language‐diverse cohort of dysphonic patients, individuals with public health insurance were significantly less likely to attend voice therapy. Language‐discordant therapy and interpreter collaboration was not a statistically significant barrier to therapy attendance. Additional investigation is warranted to optimize allocation of voice therapy resources for those with public health insurance and for diverse speakers of all languages.

Level of Evidence

4 Laryngoscope, 131:1835–1839, 2021
Thermo‐Mechanical Fractional Injury Enhances Skin Surface‐ and Epidermis‐ Protoporphyrin IX Fluorescence: Comparison of 5‐Aminolevulinic Acid in Cream and Gel Vehicles
Authors: Foged Camilla , Haedersdal Merete , Bik Liora , Dierickx Christine , Phillipsen Peter A. , Togsverd‐Bo Katrine
Published: October 2020

Background and Objectives

Thermo‐mechanical fractional injury (TMFI) impacts the skin barrier and may increase cutaneous drug uptake. This study investigated the potential of TMFI in combination with 5‐aminolevulinic acid (ALA) cream and gel formulations to enhance Protoporphyrin IX (PpIX) fluorescence at the skin surface and in the skin.

Study Design/Materials and Methods

In healthy volunteers (n = 12) a total of 144 test areas were demarcated on the upper back. Test areas were randomized to (i) TMFI (6 milliseconds, 400 µm at a single pass) or no pretreatment and (ii) 20% ALA in cream or gel formulations. Skin surface PpIX fluorescence was quantified by PpIX fluorescence photography and photometry in 30‐minute intervals until 3 hours. PpIX fluorescence microscopy quantified separate PpIX fluorescence in the epidermis, and in superficial‐, mid‐, and deep‐ dermis from punch biopsies sampled after 3 hours of ALA incubation. Local skin reactions (LSR) and pain intensities (numerical rating scale 0–10) were evaluated immediately, at 3 hours and 14 days after the intervention.

Results

TMFI exposure before photosensitizer application significantly increased skin surface PpIX fluorescence, both for ALA cream (TMFI‐ALA‐cream 7848 arbitrary units [AU] vs. ALA‐cream 5441 AU, 3 hours, P < 0.001) and ALA gel (TMFI + ALA‐gel 4591 AU vs. ALA‐gel 3723 AU, 3 hours, P < 0.001). The TMFI‐mediated increase in PpIX fluorescence was similar for ALA‐cream and ‐gel formulations (P = 0.470) at the skin surface. In the epidermis, PpIX fluorescence intensities increased from combination treatment with TMFI and ALA‐cream (TMFI + ALA‐cream 421 AU vs. ALA‐cream 293 AU, P = 0.034) but not from combination with TMFI and ALA‐gel (TMI + ALA‐gel 264 AU vs. ALA‐gel 261 AU, P = 0.791). Dermal fluorescence intensities (superficial‐, mid‐, or deep dermis) were unaffected by TMFI pretreatment in both ALA‐cream and ALA‐gel exposed skin (P = 0.339). ALA‐cream generally induced higher PpIX fluorescence intensities than ALA‐gel (skin surface P < 0.001 and epidermis P < 0.03). TMFI induced low pain intensities (median 3) and mild LSR that were resolved at 14 days follow‐up.

Conclusion

Given the present study design, TMFI, in combination with the standardized application of 20% ALA cream and gel formulations, significantly enhanced skin surface PpIX fluorescence compared to no pretreatment. Additionally, TMFI increased epidermal PpIX fluorescence combined with 20% ALA cream vehicle. Thus, TMFI pretreatment and formulation characteristics exert influence on PpIX fluorescence intensities in normal skin. Lasers Surg. Med. © 2020 Wiley Periodicals LLC
Further delineation of autosomal recessive intellectual disability syndrome caused by homozygous variant of the NSUN2 gene in a chinese pedigree
Authors: Sun Songyang , Chen Lin , Wang Yuchuan , Wang Jian , Li Niu , Wang Xike
Published: October 2020

Background

The enzyme NOP2/Sun RNA methyltransferase 2 (NSUN2) catalyzes the methylation of cytosine to 5‐methylcytosine (m5C) at position 34 of tRNA(Leu; CAA) precursors containing introns that play a vital role in spindle assembly during mitosis and chromosome segregation. Biallelic variants in the NSUN2 gene cause a rare intellectual disability that has been identified only in a few Middle Eastern patients. Affected individuals usually have other deformities, including developmental delay, short stature, microcephaly, and facial dysmorphism. The aim of this study was to identify the genetic cause of three female patients from a Chinese pedigree, who presented with similar phenotype consisting of the above clinical features.

Methods

Whole‐exome sequencing (WES) was used to screen for causal variants in the genome, and the candidate variants were subsequently verified using Sanger sequencing.

Results

WES revealed a previously unreported homozygous nonsense variant (NM_017755.5: c.1004T>A, p.Leu335*) in exon 9 of NSUN2, which was consistent with the clinical phenotype of the patients and co‐segregated with the disease in their family. A comparison of this phenotype with that of patients in published reports uncovered several novel clinical features related to NSUN2 variations, including feeding difficulties, slender hands and fingers, severely restricted finger mobility, hallux valgus, varus foot, and elevated α‐hydroxybutyrate dehydrogenase (HBDH).

Conclusions

These are the first findings of a non‐consanguineous Chinese pedigree with a homozygous NSUN2 variant. We expanded the phenotypic spectrum associated with NSUN2 variations.
A new algorithm for fractional differential equation based on fractional order reproducing kernel space
Authors: Zhang Ruimin , Lin Yingzhen
Published: October 2020

This paper develops an effective and new method to solve a class of fractional differential equations. The method is based on a fractional order reproducing kernel space. First, depending on some theories, a fractional order reproducing kernel spaceWα[0, 1] is constructed. The fractional order reproducing kernel space is a very suitable space to solve a class of fractional differential equations. Then, we calculate the reproducing kernelRy(x) of the spaceWα[0, 1] skilfully in §3. And convergence order and time complexity of this algorithm are discussed. We prove that the approximate solutionunof (1.1) converges to its exact solutionuis not less than the second order. The time complexity of the algorithm is equal to the polynomial time of the third degree. Finally, three experiments support the algorithm strongly from the aspect of theory and technique.
Bi‐objective optimization of catheter positions for high‐dose‐rate prostate brachytherapy
Authors: van der Meer Marjolein C. , Bosman Peter A.N. , Niatsetski Yury , Alderliesten Tanja , van Wieringen Niek , Pieters Bradley R. , Bel Arjan
Published: October 2020

Purpose

Bi‐objective simultaneous optimization of catheter positions and dwell times for high‐dose‐rate (HDR) prostate brachytherapy, based directly on dose‐volume indices, has shown promising results. However, optimization with the state‐of‐the‐art evolutionary algorithm MO‐RV‐GOMEA so far required several hours of runtime, and resulting catheter positions were not always clinically feasible. The aim of this study is to extend the optimization model and apply GPU parallelization to achieve clinically acceptable computation times. The resulting optimization procedure is compared with a previously introduced method based solely on geometric criteria, the adapted Centroidal Voronoi Tessellations (CVT) algorithm.

Methods

Bi‐objective simultaneous optimization was performed with a GPU‐parallelized version of MO‐RV‐GOMEA. This optimization of catheter positions and dwell times was retrospectively applied to the data of 26 patients previously treated with HDR prostate brachytherapy for 8–16 catheters (steps of 2). Optimization of catheter positions using CVT was performed in seconds, after which optimization of only the dwell times using MO‐RV‐GOMEA was performed in 1 min.

Results

Simultaneous optimization of catheter positions and dwell times using MO‐RV‐GOMEA was performed in 5 min. For 16 down to 8 catheters (steps of 2), MO‐RV‐GOMEA found plans satisfying the planning‐aims for 20, 20, 18, 14, and 11 out of the 26 patients, respectively. CVT achieved this for 19, 17, 13, 9, and 2 patients, respectively. The P‐value for the difference between MO‐RV‐GOMEA and CVT was 0.023 for 16 catheters, 0.005 for 14 catheters, and <0.001 for 12, 10, and 8 catheters.

Conclusions

With bi‐objective simultaneous optimization on a GPU, high‐quality catheter positions can now be obtained within 5 min, which is clinically acceptable, but slower than CVT. For 16 catheters, the difference between MO‐RV‐GOMEA and CVT is clinically irrelevant. For 14 catheters and less, MO‐RV‐GOMEA outperforms CVT in finding plans satisfying all planning‐aims.
MR properties of 19F C3F8 gas in the lungs of healthy volunteers: and apparent diffusion coefficient at 1.5T and at 3T
Authors: Maunder Adam , Chan Ho‐Fung , Hughes Paul J. C. , Collier Guillhem , Norquay Graham , Rodgers Oliver , Thelwall Peter , Robb Fraser , Rao Madhwesha , Wild Jim M.
Published: October 2020

Purpose

To measure the transverse relaxation time () and apparent diffusion coefficient (ADC) of 19F‐C3F8 gas in vivo in human lungs at 1.5T and 3T, and to determine the representative distribution of values of these parameters in a cohort of healthy volunteers.

Methods

Mapping of ADC at lung inflation levels of functional residual capacity (FRC) and total lung capacity (TLC) was performed with inhaled 19F‐C3F8 (eight subjects) and 129Xe (six subjects) at 1.5T. mapping with 19F‐C3F8 was performed at 1.5T (at FRC and TLC) for 8 subjects and at 3T (at TLC for seven subjects).

Results

At both FRC and TLC, the 19F‐C3F8 ADC was smaller than the free diffusion coefficient demonstrating airway microstructural diffusion restriction. From FRC to TLC, the mean ADC significantly increased from 1.56 mm2/s to 1.83 mm2/s (P = .0017) for 19F‐C3F8, and from 2.49 mm2/s to 3.38 mm2/s (P = .0015) for 129Xe. The posterior‐to‐anterior gradient in ADC for FRC versus TLC in the superior half of the lungs was measured as 0.0308 mm2/s per cm versus 0.0168 mm2/s per cm for 19F‐C3F8 and 0.0871 mm2/s per cm versus 0.0326 mm2/s per cm for 129Xe. A consistent distribution of 19F‐C3F8 values was observed in the lungs, with low values observed near the diaphragm and large pulmonary vessels. The mean across volunteers was 4.48 ms at FRC and 5.33 ms at TLC for 1.5T, and 3.78 ms at TLC for 3T.

Conclusion

In this feasibility study, values of physiologically relevant parameters of lung microstructure measurable by MRI (, and ADC) were established for C3F8 in vivo lung imaging in healthy volunteers.
Crispr‐Cas9 in der Anwendung – wo wir heute stehen
Authors: Schneider Sabine
Published: October 2020

Die Entwicklung eines bakteriellen Immunsystems zu einem Werkzeug für die Gentechnik hat nicht nur die biologische und medizinische Forschung revolutioniert. Das Werkzeug hat zudem das Potenzial, Erbkrankheiten zu heilen. Wo steht die Forschung fast acht Jahre, nachdem Crispr‐Cas9 erstmals beschrieben wurde?
Supervised segmentation framework for evaluation of diffusion tensor imaging indices in skeletal muscle
Authors: Secondulfo Laura , Ogier Augustin C. , Monte Jithsa R. , Aengevaeren Vincent L. , Bendahan David , Nederveen Aart J. , Strijkers Gustav J. , Hooijmans Melissa T.
Published: October 2020

Diffusion tensor imaging (DTI) is becoming a relevant diagnostic tool to understand muscle disease and map muscle recovery processes following physical activity or after injury. Segmenting all the individual leg muscles, necessary for quantification, is still a time‐consuming manual process. The purpose of this study was to evaluate the impact of a supervised semi‐automatic segmentation pipeline on the quantification of DTI indices in individual upper leg muscles. Longitudinally acquired MRI datasets (baseline, post‐marathon and follow‐up) of the upper legs of 11 subjects were used in this study. MR datasets consisted of a DTI and Dixon acquisition. Semi‐automatic segmentations for the upper leg muscles were performed using a transversal propagation approach developed by Ogier et al on the out‐of‐phase Dixon images at baseline. These segmentations were longitudinally propagated for the post‐marathon and follow‐up time points. Manual segmentations were performed on the water image of the Dixon for each of the time points. Dice similarity coefficients (DSCs) were calculated to compare the manual and semi‐automatic segmentations. Bland‐Altman and regression analyses were performed, to evaluate the impact of the two segmentation methods on mean diffusivity (MD), fractional anisotropy (FA) and the third eigenvalue (λ3). The average DSC for all analyzed muscles over all time points was 0.92 ± 0.01, ranging between 0.48 and 0.99. Bland‐Altman analysis showed that the 95% limits of agreement for MD, FA andλ3ranged between 0.5% and 3.0% for the transversal propagation and between 0.7% and 3.0% for the longitudinal propagations. Similarly, regression analysis showed good correlation for MD, FA andλ3(r= 0.99,p< 60; 0.0001). In conclusion, the supervised semi‐automatic segmentation framework successfully quantified DTI indices in the upper‐leg muscles compared with manual segmentation while only requiring manual input of 30% of the slices, resulting in a threefold reduction in segmentation time.
Leverage centrality analysis of infrastructure networks
Authors: Berberler Murat Erşen
Published: October 2020

Leverage centrality is a novel centrality measure proposed to identify the critical nodes that are highly influential within the network. Leverage centrality considers the extent of connectivity of a node relative to the connectivity of its neighbors. The leverage centrality of a node in a network is determined by the extent to which its direct neighbors rely on that node for information. In this paper, leverage centralities of the nodes of infrastructure networks are computed and critical nodes within the network are identified.