bluuebunny/crossref_metadata_2025 huggingface dataset:
Acceptability and feasibility of using vaginal menstrual cups among schoolgirls in rural Nepal: a qualitative pilot study
Authors: Pokhrel Diksha , Bhattarai Sabina , Emgård Malin , von Schickfus Michael , Forsberg Birger C. , Biermann Olivia
Published: January 2021

Introduction

Menstrual hygiene management can be challenging in low-income settings and among school-aged girls due to traditional beliefs, lack of knowledge and information on best hygienic practices, and limited access to appropriate and affordable menstrual hygiene products. An alternative method for menstrual hygiene management, instead of sanitary pads or tampons, is the vaginal menstrual cup. As evidence on the use of menstrual cups is relatively limited, this study aimed to explore the acceptability and feasibility of using vaginal menstrual cups among school-aged girls in Thokarpa, Sindupalchowk, Nepal.

Methods

This is an exploratory study based on four focus group discussions with a purposive sample of 28 schoolgirls between 13 and 19 years of age who were provided with vaginal menstrual cups in Thokarpa, Sindupalchowk, Nepal. The data were collected between February and March 2019, i.e. approximately three months after the distribution of the menstrual cup. Participants were included in the study if they had started their menstruation and never given birth. Conventional content analysis was applied.

Results

Most participants perceived the menstrual cup positively. Not missing a single class in school due to problems related to menstrual hygiene management was described as a major benefit. The participants found using the menstrual cup easy and convenient, and described economic and environmental advantages of using it. Cleaning the menstrual cup did not cause any problems, according to the participants. Discomforts mentioned by the participants were: pain when inserting the menstrual cup, feeling the menstrual cup sticking out of the vagina, feeling a constant urge to urinate and leakage. Concerns were related to the size, shape and texture of the menstrual cup, and that it may “get stuck” in the vagina, while relatives were said to be concerned about the use of the menstrual cup leading to reduced fertility or losing virginity.

Conclusion

The use of vaginal menstrual cups for menstrual hygiene management among schoolgirls in Thokarpa, Sindupalchowk, Nepal, appears feasible and acceptable, as it involves practical, economic and environmental advantages. However, the scale-up of menstrual cups will require resolving described concerns and discomforts and fostering peer and family support.
No observed effect on brain vasculature of Alzheimer’s disease-related mutations in the zebrafish presenilin 1 gene
Authors: Barthelson Karissa , Newman Morgan , Nowell Cameron J. , Lardelli Michael
Published: January 2021

Previously, we found that brains of adult zebrafish heterozygous for Alzheimer’s disease-related mutations in their presenilin 1 gene (psen1, orthologous to human PSEN1) show greater basal expression levels of hypoxia responsive genes relative to their wild type siblings under normoxia, suggesting hypoxic stress. In this study, we investigated whether this might be due to changes in brain vasculature. We generated and compared 3D reconstructions of GFP-labelled blood vessels of the zebrafish forebrain from heterozygous psen1 mutant zebrafish and their wild type siblings. We observed no statistically significant differences in vessel density, surface area, overall mean diameter, overall straightness, or total vessel length normalised to the volume of the telencephalon. Our findings do not support that changes in vascular morphology are responsible for the increased basal expression of hypoxia responsive genes in psen1 heterozygous mutant brains.
LncRNA CBR3-AS1 regulates of breast cancer drug sensitivity as a competing endogenous RNA through the JNK1/MEK4-mediated MAPK signal pathway
Authors: Zhang Ming , Wang Yan , Jiang Longyang , Song Xinyue , Zheng Ang , Gao Hua , Wei Minjie , Zhao Lin
Published: January 2021

Background

Adriamycin (ADR) resistance is one of the main obstacles to improving the clinical prognosis of breast cancer patients. Long noncoding RNAs (lncRNAs) can regulate cell behavior, but the role of these RNAs in the anti-ADR activity of breast cancer remains unclear. Here, we aim to investigate the imbalance of a particular long noncoding RNA, lncRNA CBR3 antisense RNA 1 (CBR3-AS1), and its role in ADR resistance.

Methods

Microarray analysis of ADR-resistant breast cancer cells was performed to identify CBR3-AS1. CCK-8 and colony formation assays were used to detect the sensitivity of breast cancer cells to ADR. Dual-luciferase reporter, RNA pulldown, IHC and western blot analyses were used to verify the relationship between the expression of CBR3-AS1, miRNA and target genes. For in vivo experiments, the effect of CBR3-AS1 on breast cancer resistance was observed in a xenograft tumor model. The role of CBR3-AS1 in influencing ADR sensitivity was verified by clinical breast cancer specimens from the TCGA, CCLE, and GDSC databases.

Results

We found that CBR3-AS1 expression was significantly increased in breast cancer tissues and was closely correlated with poor prognosis. CBR3-AS1 overexpression promoted ADR resistance in breast cancer cells in vitro and in vivo. Mechanistically, we identified that CBR3-AS1 functioned as a competitive endogenous RNA by sponging miR-25-3p. MEK4 and JNK1 of the MAPK pathway were determined to be direct downstream proteins of the CBR3-AS1/miR-25-3p axis in breast cancer cells.

Conclusions

In summary, our findings demonstrate that CBR3-AS1 plays a critical role in the chemotherapy resistance of breast cancer by mediating the miR-25-3p and MEK4/JNK1 regulatory axes. The potential of CBR3-AS1 as a targetable oncogene and therapeutic biomarker of breast cancer was identified.
DYSMORPHIC features and adult short stature: possible clinical markers of KBG syndrome
Authors: Mattei Davide , Cavarzere Paolo , Gaudino Rossella , Antoniazzi Franco , Piacentini Giorgio
Published: January 2021

Background

Growth monitoring is an essential part of primary health care in children and short stature is frequently regarded as a relatively early sign of poor health. The association of short stature and dysmorphic features should always lead to exclude an underlying syndromic disorder.

Case presentation

We report the case of an Indian school-aged boy with dysmorphic features, intellectual disability and a clinical history characterized by seizures and hearing problems. Although his height was always included in the normal range for age and sex throughout childhood, he presented a short near-adult stature in relation to his mid-parent sex-adjusted target height. This is probably due to a rapidly progressive pubertal development.

Conclusions

In the presence of characteristic dysmorphic features, intellectual disability, seizures and hearing problems, KBG syndrome should always be considered. This emergent condition presents a wide spectrum of clinical phenotypes and is often associated with adult short stature.
Management of pediatric post-infectious neurological syndromes
Authors: Bozzola Elena , Spina Giulia , Valeriani Massimiliano , Papetti Laura , Ursitti Fabiana , Agostiniani Rino , Mascolo Cristina , Ruggiero Margherita , Di Camillo Chiara , Quondamcarlo Anna , Matera Luigi , Vecchio Davide , Memo Luigi , Villani Alberto
Published: January 2021

Background

Post-Infectious Neurological Syndromes (PINS) are heterogeneous neurological disorders with post or para-infectious onset. PINS diagnosis is complex, mainly related to the absence of any recognized guidelines and a univocal definition.

Aim of the study

To elaborate a diagnostic guide for PINS.

Materials and methods

We retrospectively analysed patients younger than 14 years old admitted to Bambino Gesù Children’s Hospital in Rome for PINS from December 2005 to March 2018. Scientific literature using PubMed as research platform was analysed: the key words “Post-Infectious Neurological Syndromes” were used.

Results

A polysymptomatic presentation occurred in a percentage of 88% of the children. Motor signs and visual disturbances the most observed symptoms/signs were the most detached, followed by fever, speech disturbances, sleepiness, headache and bradipsychism. Blood investigations are compatible with inflammation, as a prodromal illnesses was documented in most cases. Normal cerebral spinal fluid (CSF) characteristics has been found in the majority of the study population. Magnetic resonance imaging (MRI) was positive for demyelinating lesions. Antibiotics, acyclovir and steroids have been given as treatment.

Discussion

We suggest diagnostic criteria for diagnosis of PINS, considering the following parameters: neurological symptoms, timing of disease onset, blood and CSF laboratory tests, MRI imaging.

Conclusions

We propose criteria to guide clinician to diagnose PINS as definitive, probable or possible. Further studies are required to validate diagnostic criteria.
Author Correction: High-resolution analysis of cell-state transitions in yeast suggests widespread transcriptional tuning by alternative starts
Authors: Chia Minghao , Li Cai , Marques Sueli , Pelechano Vicente , Luscombe Nicholas M. , van Werven Folkert J.
Published: January 2021

An amendment to this paper has been published and can be accessed via the original article.
Efficacy of different spinal cord stimulation paradigms for the treatment of chronic neuropathic pain (PARS-trial): study protocol for a double-blinded, randomized, and placebo-controlled crossover trial
Authors: Ahmadi Rezvan , Campos Benito , Hajiabadi Mohammad Mehdi , Doerr-Harim Colette , Tenckhoff Solveig , Rasche Dirk , Unterberg Andreas , Vesper Jan , Bruckner Tom , Tronnier Volker
Published: January 2021

Background

Spinal cord stimulation (SCS) is an effective method to treat neuropathic pain; however, it is challenging to compare different stimulation modalities in an individual patient, and thus, it is largely unknown which of the many available SCS modalities is most effective. Specifically, electrodes leading out through the skin would have to be consecutively connected to different, incompatible SCS devices and be tested over a time period of several weeks or even months. The risk of wound infections for such a study would be unacceptably high and blinding of the trial difficult. The PARS-trial seizes the capacity of a new type of wireless SCS device, which enables a blinded and systematic intra-patient comparison of different SCS modalities over extended time periods and without increasing wound infection rates.

Methods

The PARS-trial is designed as a double-blinded, randomized, and placebo-controlled multi-center crossover study. It will compare the clinical effectiveness of the three most relevant SCS paradigms in individual patients. The trial will recruit 60 patients suffering from intractable neuropathic pain of the lower extremities, who have been considered for SCS therapy and were already implanted with a wireless SCS device prior to study participation. Over a time period of 35 days, patients will be treated consecutively with three different SCS paradigms (“burst,” “1 kHz,” and “1.499 kHz”) and placebo stimulation. Each SCS paradigm will be applied for 5 days with a washout period of 70 h between stimulation cycles. The primary endpoint of the study is the level of pain self-assessment on the visual analogue scale after 5 days of SCS.

Secondary, exploratory endpoints include self-assessment of pain quality (as determined by painDETECT questionnaire), quality of life (as determined by Quality of Life EQ-5D-5L questionnaire), anxiety perception (as determined by the Hospital Anxiety and Depression Scale), and physical restriction (as determined by the Oswestry Disability Index).

Discussion

Combining paresthesia-free SCS modalities with wireless SCS offers a unique opportunity for a blinded and systematic comparison of different SCS modalities in individual patients. This trial will advance our understanding of the clinical effectiveness of the most relevant SCS paradigms.

Trial registration

German Clinical Trials Register, DRKS00018929. Registered on 14 January 2020.
Blocking drug efflux mechanisms facilitate genome engineering process in hypercellulolytic fungus, Penicillium funiculosum NCIM1228
Authors: Randhawa Anmoldeep , Pasari Nandita , Sinha Tulika , Gupta Mayank , Nair Anju M. , Ogunyewo Olusola A. , Verma Sandhya , Verma Praveen Kumar , Yazdani Syed Shams
Published: January 2021

Background

Penicillium funiculosumNCIM1228 is a non-model filamentous fungus that produces high-quality secretome for lignocellulosic biomass saccharification. Despite having desirable traits to be an industrial workhorse,P. funiculosumhas been underestimated due to a lack of reliable genetic engineering tools. Tolerance towards common fungal antibiotics had been one of the major hindrances towards development of reliable transformation tools against the non-model fungi. In this study, we sought to understand the mechanism of drug tolerance ofP. funiculosumand the provision to counter it. We then attempted to identify a robust method of transformation for genome engineering of this fungus.

Results

Penicillium funiculosumshowed a high degree of drug tolerance towards hygromycin, zeocin and nourseothricin, thereby hindering their use as selectable markers to obtain recombinant transformants. Transcriptome analysis suggested a high level expression of efflux pumps belonging to ABC and MFS family, especially when complex carbon was used in growth media. Antibiotic selection medium was optimized using a combination of efflux pump inhibitors and suitable carbon source to prevent drug tolerability. Protoplast-mediated andAgrobacterium-mediated transformation were attempted for identifying efficiencies of linear and circular DNA in performing genetic manipulation. After finding Ti-plasmid-basedAgrobacterium-mediated transformation more suitable forP. funiculosum, we improvised the system to achieve random and homologous recombination-based gene integration and deletion, respectively. We found single-copy random integration of the T-DNA cassette and could achieve 60% efficiency in homologous recombination-based gene deletions. A faster, plasmid-free, and protoplast-based CRISPR/Cas9 gene-editing system was also developed forP. funiculosum. To show its utility inP. funiculosum, we deleted the gene coding for the most abundant cellulase Cellobiohydrolase I (CBH1) using a pair of sgRNA directed towards both ends ofcbh1open reading frame. Functional analysis of ∆cbh1strain revealed its essentiality for the cellulolytic trait ofP. funiculosumsecretome.

Conclusions

In this study, we addressed drug tolerability ofP. funiculosumand developed an optimized toolkit for its genome modification. Hence, we set the foundation for gene function analysis and further genetic improvements ofP. funiculosumusing both traditional and advanced methods.
Improvement of sensory neuron growth and survival via negatively regulating PTEN by miR-21-5p-contained small extracellular vesicles from skin precursor-derived Schwann cells
Authors: Cong Meng , Shen Mi , Wu Xia , Li Yan , Wang Liting , He Qianru , Shi Haiyan , Ding Fei
Published: January 2021

Background

Patients with peripheral nerve injury (PNI) often suffer from hypoxic ischemic impairments, in particular when combined with vascular damage, causing neuronal dysfunction and death. Increasing attention has been paid on skin precursor-derived Schwann cells (SKP-SCs), and previous study has shown that SKP-SCs could promote sensory recovery after cell therapy for PNI, resembling the effect of naive SCs, and SKP-SC-derived extracellular vesicles (SKP-SC-EVs) are putatively supposed to be promising therapeutic agents for neural regeneration.

Methods

SKPs were induced to differentiate towards SCs with cocktail factors (N2, neuregulin-1β, and forskolin) in vitro. SKP-SC-EVs were isolated by exoEasy Maxi Kit and characterized by morphology and phenotypic markers of EVs. Rat sensory neurons from dorsal root ganglions (DRGs) were primarily cultured in regular condition or exposed to oxygen-glucose-deprivation (OGD) condition. SKP-SC-EVs were applied to DRGs or sensory neurons, with LY294002 (a PI3K inhibitor) added; the effect on neurite outgrowth and cell survival was observed. Moreover, microRNA (miR) candidate contained in SKP-SC-EVs was screened out, and miR-mimics were transfected into DRG neurons; meanwhile, the negative regulation of PTEN/PI3K/Akt axis and downstream signaling molecules were determined.

Results

It was shown that SKP-SC-EVs could improve the neurite outgrowth of DRGs and sensory neurons. Furthermore, SKP-SC-EVs enhanced the survival of sensory neurons after OGD exposure by alleviating neuronal apoptosis and strengthening cell viability, and the expression of GAP43 (a neuron functional protein) in neurons was upregulated. Moreover, the neuro-reparative role of SKP-SC-EVs was implicated in the activation of PI3K/Akt, mTOR, and p70S6k, as well as the reduction of Bax/Bcl-2 ratio, that was compromised by LY294002 to some extent. In addition, transferring miR-21-5p mimics into sensory neurons could partly protect them from OGD-induced impairment.

Conclusions

Sum up, SKP-SC-EVs could improve neurite outgrowth of DRG sensory neurons in physiological and pathological condition. Moreover, the in vitro therapeutic potential of SKP-SC-EVs on the survival and restoration of OGD-injured sensory neurons was evidenced to be associated with miR-21-5p contained in the small EVs and miR-21-5p/PTEN/PI3K/Akt axis.

Graphic abstract
CD9, a potential leukemia stem cell marker, regulates drug resistance and leukemia development in acute myeloid leukemia
Authors: Liu Yongliang , Wang Guiqin , Zhang Jiasi , Chen Xue , Xu Huailong , Heng Gang , Chen Jun , Zhao Yongchun , Li Jiatao , Ni Yuanli , Zhang Yingzi , Shan Juanjuan , Qian Cheng
Published: January 2021

Background

Leukemia stem cells (LSCs) are responsible for the initiation, progression, and relapse of acute myeloid leukemia (AML). Therefore, a therapeutic strategy targeting LSCs is a potential approach to eradicate AML. In this study, we aimed to identify LSC-specific surface markers and uncover the underlying mechanism of AML LSCs.

Methods

Microarray gene expression data were used to investigate candidate AML-LSC-specific markers. CD9 expression in AML cell lines, patients with AML, and normal donors was evaluated by flow cytometry (FC). The biological characteristics of CD9-positive (CD9+) cells were analyzed by in vitro proliferation, chemotherapeutic drug resistance, migration, and in vivo xenotransplantation assays. The molecular mechanism involved in CD9+ cell function was investigated by gene expression profiling. The effects of alpha-2-macroglobulin (A2M) on CD9+ cells were analyzed with regard to proliferation, drug resistance, and migration.

Results

CD9, a cell surface protein, was specifically expressed on AML LSCs but barely detected on normal hematopoietic stem cells (HSCs). CD9+ cells exhibit more resistance to chemotherapy drugs and higher migration potential than do CD9-negative (CD9−) cells. More importantly, CD9+ cells possess the ability to reconstitute human AML in immunocompromised mice and promote leukemia growth, suggesting that CD9+ cells define the LSC population. Furthermore, we identified that A2M plays a crucial role in maintaining CD9+ LSC stemness. Knockdown of A2M impairs drug resistance and migration of CD9+ cells.

Conclusion

Our findings suggest that CD9 is a new biomarker of AML LSCs and is a promising therapeutic target.
Higher anticoagulation targets and risk of thrombotic events in severe COVID-19 patients: bi-center cohort study
Authors:   for the CRICS TRIGGERSEP Group (Clinical Research in Intensive Care Sepsis Trial Group for Global EvaluationResearch in Sepsis), Helms Julie , Severac François , Merdji Hamid , Schenck Maleka , Clere-Jehl Raphaël , Baldacini Mathieu , Ohana Mickaël , Grunebaum Lélia , Castelain Vincent , Anglés-Cano Eduardo , Sattler Laurent , Meziani Ferhat
Published: January 2021

Background

Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (ICUs) from two centers of a French tertiary hospital were included in our cohort study. Patients were compared according to their anticoagulant treatment to evaluate the risk/benefit of prophylactic anticoagulation versus therapeutic anticoagulation. Medical history, symptoms, biological data and imaging were prospectively collected.

Results

One hundred and seventy-nine patients (73% men) were analyzed: 108 in prophylactic group and 71 in therapeutic group. Median age and SAPS II were 62 [IQR 51; 70] years and 47 [IQR 37; 63] points. ICU mortality rate was 17.3%. Fifty-seven patients developed clinically relevant thrombotic complications during their ICU stay, less frequently in therapeutic group (adjusted OR 0.38 [0.14–0.94], p = 0.04). The occurrences of pulmonary embolism (PE), deep vein thrombosis (DVT) and ischemic stroke were significantly lower in the therapeutic group (respective adjusted OR for PE: 0.19 [0.03–0.81]; DVT: 0.13 [0.01–0.89], stroke: 0.06 [0–0.68], all p < 0.05). The occurrence of bleeding complications was not significantly different between groups, neither were ICU length of stay or mortality rate. D-dimer levels were significantly lower during ICU stay, and aPTT ratio was more prolonged in the therapeutic group (p < 0.05).

Conclusion

Increasing the anticoagulation of severe COVID-19 patients to a therapeutic level might decrease thrombotic complications without increasing their bleeding risk.
Joint optimization of computing ratio and access points’ density for mixed mobile edge/cloud computing
Authors: Jing Tianqi , He Shiwen , Yu Fei , Huang Yongming , Yang Luxi , Ren Ju
Published: January 2021

Cooperation between the mobile edge computing (MEC) and the mobile cloud computing (MCC) in offloading computing could improve quality of service (QoS) of user equipments (UEs) with computation-intensive tasks. In this paper, in order to minimize the expect charge, we focus on the problem of how to offload the computation-intensive task from the resource-scarce UE to access point’s (AP) and the cloud, and the density allocation of APs’ at mobile edge. We consider three offloading computing modes and focus on the coverage probability of each mode and corresponding ergodic rates. The resulting optimization problem is a mixed-integer and non-convex problem in the objective function and constraints. We propose a low-complexity suboptimal algorithm called Iteration of Convex Optimization and Nonlinear Programming (ICONP) to solve it. Numerical results verify the better performance of our proposed algorithm. Optimal computing ratios and APs’ density allocation contribute to the charge saving.
A new task offloading algorithm in edge computing
Authors: Zhang Zhenjiang , Li Chen , Peng ShengLung , Pei Xintong
Published: January 2021

In the last few years, the Internet of Things (IOT), as a new disruptive technology, has gradually changed the world. With the prosperous development of the mobile Internet and the rapid growth of the Internet of Things, various new applications continue to emerge, such as mobile payment, face recognition, wearable devices, driverless, VR/AR, etc. Although the computing power of mobile terminals is getting higher and the traditional cloud computing model has higher computing power, it is often accompanied by higher latency and cannot meet the needs of users. In order to reduce user delay to improve user experience, and at the same time reduce network load to a certain extent, edge computing, as an application of IOT, came into being. In view of the new architecture after dating edge computing, this paper focuses on the task offloading in edge computing, from task migration in multi-user scenarios and edge server resource management expansion, and proposes a multi-agent load balancing distribution based on deep reinforcement learning DTOMALB, a distributed task allocation algorithm, can perform a reasonable offload method for this scenario to improve user experience and balance resource utilization. Simulations show that the algorithm has a certain adaptability compared to the traditional algorithm in the scenario of multi-user single cell, and reduces the complexity of the algorithm compared to the centralized algorithm, and reduces the average response delay of the overall user. And balance the load of each edge computing server, improve the robustness and scalability of the system.
A fixed point theorem for generalized $(\psi ,\varphi )$-weak contractions in Branciari type generalized metric spaces
Authors: Xue Zhiqun , Lv Guiwen
Published: January 2021

In this paper, we obtain a new convergence theorem for fixed points of weak contractions in Branciari type generalized metric spaces under weaker conditions. The proof process of the theorem is new and different from that of other authors. An illustrative example of this theorem is to show how the new conditions extend known results.
Self-adaptive trajectory prediction for improving traffic safety in cloud-edge based transportation systems
Authors: Xie Bin , Zhang Kun , Zhao Yi , Zhang Yunchun , Cai Ying , Wang Tian
Published: January 2021

Intelligent transportation brings huge benefits to humans’ life and Industrial production in terms of vehicle control and traffic management. Now, the development of edge-cloud computing has once again promoted intelligent transportation into a new era. However, the development of intelligent transportation inevitably produces a large amount of data, which brings new challenges to data privacy protection and security. In this paper, we propose to develop an improved trajectory prediction framework based on the self-adaptive trajectory prediction model (SATP), which could significantly enhance traffic safety in transportation systems. The proposed framework is capable of guaranteeing the accurate trajectory prediction of moving target under different application scenarios. In particular, to reduce the size of original trajectory point data collected by sensors, the angle change and minimum description length (MDL) principle are first combined to remove the redundant points in raw trajectories. The obtained points can then be reduced for model using the two-step clustering method. To further enhance the prediction performance, we add the “self-transfer” to the original model to solve the problems that the state of original SATP model may be discontinuous. Furthermore, we propose to develop a trajectory complementation method based on Bezier curve to improve the prediction accuracy. Finally, by comparing the two-step clustering method with the commonly-used SinglePass and density-based clustering method (DBCM) algorithms, the proposed two-step clustering policy greatly reduce the time cost of clustering. At the same time, by comparing the improved SATP model with the original model, the results show that the improved SATP method can greatly improve the speed of prediction model.
Spatial and temporal scales of coral reef fish ecological research and management: a systematic map protocol
Authors: Lawrence Alice , Heenan Adel , Levine Arielle , Haddaway Neal R. , Powell Farrah , Wedding Lisa , Roche Ronan , Lawrence Peter , Szostek Claire , Ford Helen , Southworth Lucy , Pilly Sivajyodee Sannassy , Richardson Laura E. , Williams Gareth J.
Published: January 2021

Background

Coral reefs are rapidly changing in response to local and global stressors. Research to better understand and inform the management of these stressors is burgeoning. However, in situ studies of coral reef ecology are constrained by complex logistics and limited resources. Many reef studies are also hampered by the scale-dependent nature of ecological patterns, and inferences made on causal relationships within coral reef systems are limited by the scales of observation. This is because most socio-ecological studies are conducted at scales relevant to the phenomenon of interest. However, management often occurs across a significantly broader, often geopolitical, range of scales. While there is a critical need for incisive coral reef management actions at relevant spatial and temporal scales, it remains unclear to what extent the scales of empirical study overlap with the scales at which management inferences and recommendations are made. This systematic map protocol will evaluate this potential scale mismatch with the goal of raising awareness about the significance of effectively addressing and reporting the scales at which researchers collect data and make assumptions.

Methods

We will use the Collaboration for Environmental Evidence (CEE) systematic mapping guidelines to identify relevant studies using a framework-based synthesis to summarise the spatial and temporal scales of coral reef fish ecology research and the scales at which management inferences or recommendations are made. Using tested predefined terms, we will search for relevant published academic and grey literature, including bibliographic databases, web-based search engines, and organisational websites. Inclusion criteria for the evidence map are empirical studies that focus on coral reef fish ecological organisation and processes, those informing management interventions and policy decisions, and management documents that cite coral reef research for management decision-making. Study results will be displayed graphically using data matrices and heat maps. This is the first attempt to systematically assess and compare the scales of socio-ecological research conducted on coral reef systems with their management.
The prospective evaluation and risk factors of dysphagia after surgery in patients with oral cancer
Authors: Hasegawa Takumi , Yatagai Nanae , Furukawa Tatsuya , Wakui Emi , Saito Izumi , Takeda Daisuke , Kakei Yasumasa , Sakakibara Akiko , Nibu Ken-ichi , Akashi Masaya
Published: January 2021

Background

This prospective study investigated the change of swallowing ability using the Swallowing Ability Scale System (SASS) and swallowing-related quality of life (QOL) by Performance Status Scale for Head and Neck Cancer patients (PSS-H&N). This study also investigated the risk factors for postoperative dysphagia in patients who received reconstructive surgery for oral cancer.

Subjects and Methods

This study included 64 patients (33 men and 31 women) who underwent radical surgery with neck dissection and reconstructive surgery for oral cancers between July 2014 and February 2018. We evaluated risk factors for poor swallowing ability after treatment, including demographic factors, preoperative factors and perioperative factors, with univariate and multivariate analyses. The change of swallowing ability by the SASS and swallowing-related QOL by PSS-H&N were evaluated prospectively prior to the initiation of surgery within 1 week and at 1 and 3 months after treatment.

Results

Advanced T stage (T3, 4) (odds ratio (OR) = 79.71), bilateral neck dissection (OR = 20.66) and the resection of unilateral or bilateral suprahyoid muscles (OR = 17.00) were associated with poor swallowing ability after treatment. The scores for time for food intake and Eating in Public were associated with decrease of QOL in the poor group.

Conclusions

We propose that clinicians consider the risk factors identified in this study and pay close attention to the management of oral cancer patients with reconstructive surgery.

Graphical Abstract
Addressing the medicines access challenge through balance, evidence, collaboration and transparency: key take-away lessons of the 4th PPRI Conference
Authors: Vogler Sabine , Zimmermann Nina , Babar Zaheer-Ud-Din , Busse Reinhard , Espin Jaime , Mantel-Teeuwisse Aukje K. , Panteli Dimitra , Suleman Fatima , Wirtz Veronika J.
Published: January 2021

The 4th PPRI Conference, held in Vienna in October 2019, addressed issues related to equitable and affordable access to medicines. A multi-stakeholder audience from around the globe discussed solutions and best practice models for current challenges such as high-priced medicines, limitations of current pricing and reimbursement policies and tight budgets for health technologies. A multi-faceted approach (so-called balance, evidence, collaboration and transparency/BECT strategy) was also discussed. This includes an improved balance of different interests and policy areas, generation of relevant evidence, collaboration between countries and stakeholders, and transparency, and was considered as the most promising pathway for the future.
Health-Related Quality of Life Data in Cancer Clinical Trials for Drug Registration: The Value Beyond Reimbursement
Authors: Wasalski Erinne , Mehta Shashi
Published: January 2021

PURPOSE

A review of the literature was performed to evaluate how quality of life measures are collected, analyzed, and reported in cancer clinical trials intended to support drug registration.Health-related quality of life (HRQoL) data points are one of the patient-reported outcome (PRO) assessments used in clinical trials to evaluate the effects of treatments from the patient perspective. The use of PROs has gained focus in cancer clinical trials as more options become available for greater longevity of patients on treatment. Standardization of PRO data is evolving and involves unique challenges when used for assessing biologic and chemotherapeutic agents for the treatment of cancer.

METHODS

In this study, a review of literature published between 2009 and 2019 was conducted using PubMed, COCHRANE Library, and Medline. The research focus was on the current guidance, implementation, and reporting as well as highlighting the issues, and recommendations for the inclusion of HRQoL end points in cancer clinical trials intended for use in drug registration.

RESULTS

Although there exist many levels of guidance for HRQoL measures in cancer drug trials, challenges to operational implementation, the current inconsistent adherence to reporting standards, and the lack of consensus and understanding of analyses limit the value and potential of the resulting data collected.

CONCLUSION

The results of HRQoL data collected from cancer clinical trials can be difficult to interpret and apply to inform clinical decision making. Increased reporting and access to these data can provide opportunities for potential applications to improve translatability of HRQoL data collected in clinical trials into practice.
Squamous Cell Carcinoma of the Anus Incidence, Mortality, and Survival Among the General Population and Persons Living With HIV in Puerto Rico, 2000-2016
Authors: Ortiz-Ortiz Karen J. , Ramos-Cartagena Jeslie M. , Deshmukh Ashish A. , Torres-Cintrón Carlos R. , Colón-López Vivian , Ortiz Ana P.
Published: January 2021

PURPOSE

Squamous cell carcinoma of the anus (SCCA) is common among persons living with HIV (PLWH). We described SCCA incidence and survival among the general population and among PLWH in Puerto Rico (PR), along with mortality of anal cancer.

METHODS

PR HIV/AIDS Surveillance Program and the PR Central Cancer Registry databases were linked (2000-2016). Incidence rates (IRs) and trends (annual percent change [APC]) in SCCA and mortality rates and trends for anal cancer were estimated. Relative survival and relative excess risk (RER) of death were calculated.

RESULTS

From 2000 to 2016, 991 individuals in PR were diagnosed with anal cancer; 73% of cases were SCCA 9.1% of SCCA and 1.5% of non-SCCA cases were in PLWH ( P < .0001). SCCA incidence was higher among PLWH than the general population (IR = 27.7/100,000). Among PLWH, SCCA incidence (per 100,000) was the highest among men who have sex with men (IR = 60.5). From 2001-2016, SCCA incidence increased among the general population (APC: 4.90, P < .05); however, no significant change was observed among PLWH (APC = 0.19 and P = .96). The APC for anal cancer mortality in the general population was positive (3.9%) from 2000 to 2016, but not significant ( P > .05). The 5-year relative survival of SCCA was 56.9% among PLWH and 66.8% among the general population. In multivariate analysis, the RER of death for SCCA 5 years postdiagnosis was affected by stage at diagnosis (distant: RER = 7.6, 95% CI, 2.36 to 24.25) but not by PLWH status (RER = 1.4, 95% CI, 0.67 to 3.01).

CONCLUSION

Our findings highlight the relevance of anal cancer screening in PLWH and HPV vaccination in both PLWH and the general population in PR, which could have an impact on the disease trend in the next few decades.
Multisector Collaborations and Global Oncology: The Only Way Forward
Authors: Blanchard Charmaine , Lubuzo Buhle , Asirwa Frederick Chite , Dlamini Xolisile , Msadabwe-Chikuni Susan C. , Mwachiro Michael , Shyirambere Cyprien , Ruhangaza Deo , Milner Dan A. , Van Loon Katherine , DeBoer Rebecca , Mtshali Phangisile , Dugan Ute , Baker Ellen , Shulman Lawrence N.
Published: January 2021

PURPOSE

At the 12th meeting of AORTIC (African Organization for Research and Training in Cancer) in Maputo, Mozambique, held between November 5 and November 8, 2019, a special workshop was organized to focus on the need for collaboration and coordination between governments and health systems in Africa with academic, industry, association, and other nongovernmental organizations to effect sustainable positive change for the care of patients with cancer.

METHODS

Representatives from seven different projects in Africa presented implementation science and demonstration projects of their to date efforts in cancer system improvement including patient access, South-South partnerships, in-country specialized training, palliative care consortium, treatment outcomes, and focused pathology and diagnostic capacity building. Key partners of the various projects served as moderators and commentators during the session.

RESULTS

From across all the presentations, lessons learned and exemplary evidence of the value of partnerships were gathered and summarized.

CONCLUSION

The concluding synthesis of the presentations determined that with the broad needs across cancer requiring in-depth expertise at each point on a patient’s journey, no single organization can effect change alone. Multipartner collaborations not only should be the norm but should also be coordinated so that efforts are not duplicated and maximum patient access to cancer diagnosis and care is achieved.
Incidence and Predictors of Mental Health Outcomes Among Survivors of Adolescent and Young Adult Cancer: A Population-Based Study Using the IMPACT Cohort
Authors: De Riddhita , Sutradhar Rinku , Kurdyak Paul , Aktar Suriya , Pole Jason D. , Baxter Nancy , Nathan Paul C. , Gupta Sumit
Published: January 2021

PURPOSE

Risk and predictors of long-term mental health outcomes in survivors of adolescent and young adult (AYA) cancers are poorly characterized. Mental health is consequently neglected in long-term follow-up.

METHODS

We identified all AYA in Ontario, Canada age 15-21 years when diagnosed with one of six common cancers between 1992-2012 using a population-based database, and compared them with matched controls. Linkage to provincial healthcare data allowed analysis of rates of outpatient (family physician and psychiatrist) visits for psychiatric indications and time to severe psychiatric events (emergency room visit, hospitalization, and suicide). Demographic-, disease-, and treatment-related predictors of adverse outcomes, including treatment setting (adult v pediatric), were examined.

RESULTS

Among 2,208 survivors and 10,457 matched controls, 5-year survivors experienced higher rates of outpatient mental health visits than controls (671 visits per 1,000 person-years v 506; adjusted rate ratio [RR] 1.3; 95% CI, 1.1 to 1.5; P = .006). Risk of a severe psychiatric episode was also increased among survivors (adjusted hazard ratio [HR], 1.2; 95% CI, 1.1 to 1.4, P = .008). Risk of a psychotic disorder–associated severe event was doubled in survivors (HR, 2.0, 95% CI, 1.3 to 2.4; P = .007) although absolute risk remained low (15-year cumulative incidence 1.7%; 95% CI, 1.0 to 2.7). In multivariable analysis, survivors treated in adult centers experienced substantially higher outpatient visit rates compared with those treated in pediatric settings (RR 1.8; 95% CI, 1.0 to 3.1; P = .04).

CONCLUSION

Survivors of AYA cancer are at substantially increased risk of adverse mental health outcomes, with those treated in adult centers at particular risk. Although absolute incidence was low, survivors were at increased risk of psychotic disorder–associated severe events. Long-term mental health surveillance is warranted, as is research into effective interventions during or after cancer treatment.
Ceramides mediate positional signals in Arabidopsis thaliana protoderm differentiation
Authors: Nagata Kenji , Ishikawa Toshiki , Kawai-Yamada Maki , Takahashi Taku , Abe Mitsutomo
Published: January 2021

The differentiation of distinct cell types in appropriate patterns is a fundamental process in the development of multicellular organisms. In Arabidopsis thaliana, protoderm/epidermis differentiates as a single cell layer at the outermost position. However, little is known about the molecular nature of the positional signals that achieve correct epidermal cell differentiation. Here, we propose that very-long-chain fatty acid-containing ceramides (VLCFA-Cers) mediate positional signals by stimulating the function of ARABIDOPSIS THALIANA MERISTEM LAYER1 (ATML1), a master regulator of protoderm/epidermis differentiation, during lateral root development. We show that VLCFA-Cers, which are synthesized predominantly in the outermost cells, bind to the lipid-binding domain of ATML1. Importantly, this cell type-specific protein-lipid association alters the activity of ATML1 protein and consequently restricts its expression to the protoderm/epidermis through a transcriptional feedback loop. Furthermore, establishment of a compartment, enriched with VLCFA-containing sphingolipids, at the outer lateral membrane facing the external environment may function as a determinant of protodermal cell fate. Taken together, our results indicate that VLCFA-Cers play a pivotal role in directing protoderm/epidermis differentiation by mediating positional signals to ATML1.

This article has an associated ‘The people behind the papers’ interview.
Control of SRC molecular dynamics encodes distinct cytoskeletal responses by specifying signaling pathway usage
Authors: Kerjouan Adèle , Boyault Cyril , Oddou Christiane , Hiriart-Bryant Edwige , Grichine Alexei , Kraut Alexandra , Pezet Mylène , Balland Martial , Faurobert Eva , Bonnet Isabelle , Coute Yohann , Fourcade Bertrand , Albiges-Rizo Corinne , Destaing Olivier
Published: January 2021

Upon activation by different transmembrane receptors, the same signaling protein can induce distinct cellular responses. A way to decipher the mechanisms of such pleiotropic signaling activity is to directly manipulate the decision-making activity that supports the selection between distinct cellular responses. We developed an optogenetic probe (optoSRC) to control SRC signaling, an example of a pleiotropic signaling node, and we demonstrated its ability to generate different acto-adhesive structures (lamellipodia or invadosomes) upon distinct spatio-temporal control of SRC kinase activity. The occurrence of each acto-adhesive structure was simply dictated by the dynamics of optoSRC nanoclusters in adhesive sites, which were dependent on the SH3 and Unique domains of the protein. The different decision-making events regulated by optoSRC dynamics induced distinct downstream signaling pathways, which we characterized using time-resolved proteomic and network analyses. Collectively, by manipulating the molecular mobility of SRC kinase activity, these experiments reveal the pleiotropy-encoding mechanism of SRC signaling.
Association between 18F-FDG metabolic activity and programmed death ligand-1 (PD-L1) expression using 22C3 immunohistochemistry assays in non-small cell lung cancer (NSCLC) resection specimens
Authors: Zhao Long , Liu Jinjun , Wang Huoqiang , Shi Jingyun
Published: January 2021

Objective:

This study sought to investigate the association between 18F-fludeoxyglucose (18F-FDG) uptake in positron emission tomography/CT (PET/CT) scans and different programmed death ligand-1 (PD-L1) expression conditions in non-small cell lung cancer (NSCLC).

Methods:

From October 2017 to December 2019, NSCLC was retrospectively identified in 419 consecutive patients who underwent 18F-FDG PET/CT scans and PD-L1 expression tests using the PD-L1 22C3 assay. The association between clinicopathological characteristics and PD-L1 expression was assessed.

Results:

The frequency of PD-L1-positive tumours was 38.2% (160/419) in NSCLC. In NSCLC, the multivariate analysis showed a high maximum standardised uptake value (SUVmax) (p < 0.0001) and an EGFR wild type genotype (p = 0.027) was significantly associated with PD-L1-positivity. In adenocarcinoma (ADC), the multivariate analysis showed that a high SUVmax (p < 0.0001) was significantly associated with PD-L1-positivity. In NSCLC and ADC, a Mann–Whitney U test showed significant differences between groups with PD-L1 high expression and PD-L1 low expression levels in terms of SUVmax (p = 0.011 and p = 0.013, respectively). The results of the receiver operating characteristic curve analysis showed that the area under the curve of the SUVmax was 0.767 (95% CI, 0.720–0.814; p < 0.0001) and 0.712 (95% CI, 0.651–0.774; p < 0.0001) in NSCLC and ADC, respectively.

Conclusion:

The study demonstrates that the SUVmax was significantly associated with PD-L1 expression in NSCLC and ADC. The SUVmax was significantly different between the PD-L1 high and low expression conditions, as quantified using a PD-L1 22C3 assay.

Advances in knowledge:

This study provides direct evidence that SUVmax as a metabolic biomarker may help select patients with NSCLC likely to benefit from pembrolizumab.
Introduction: Angloclassical?
Authors: Nikolaou Paschalis
Published: January 2021

Introduction