bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex difference for the risk of amputation in diabetic patients: A systematic review and meta-analysis
Authors: Fan Lei , Wu Xue-Jian
Published: March 2021

The risk of amputation is a sequelae of diabetic foot ulceration, which are significantly increased in diabetic patients and caused huge morbidly and mortality. However, whether the risk amputation in diabetic patients are differing in male and female remains inconclusive. We therefore conducted a systematic review and meta-analysis to assess the sex difference for the risk of amputation in diabetic patients. We systematically searched PubMed, EmBase, and the Cochrane library to identify eligible study from their inception up to November 2020. The diagnostic value of male patients on subsequent amputation risk were assessed by using sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic odds ratio (DOR), and area under the receiver operating characteristic curve (AUC). Twenty-two studies recruited a total of 33,686,171 diabetic patients were selected for quantitative analysis. The risk of amputation in male diabetic patients was greater than female diabetic patients (DOR: 1.38; 95%CI: 1.13–1.70;P<0.001). The sensitivity and specificity for male diabetic patients on the risk of amputation were 0.72 (95%CI: 0.72–0.73), and 0.51 (95%CI: 0.51–0.51), respectively. Moreover, the PLR and NLR of male diabetic patients for predicting amputation were 1.13 (95%CI: 1.05–1.22), and 0.82 (0.72–0.94), respectively. Furthermore, the AUC for male diabetic patients on amputation risk was 0.56 (95%CI: 0.48–0.63). This study found male diabetic patients was associated with an increased risk of amputation than female diabetic patients, and the predictive value of sex difference on amputation risk in diabetic patients was mild.
Explaining placebo effects in an online survey study: Does ‘Pavlov’ ring a bell?
Authors: Smits Rosanne M. , Veldhuijzen Dieuwke S. , Olde Hartman Tim , Peerdeman Kaya J. , Van Vliet Liesbeth M. , Van Middendorp Henriët , Rippe Ralph C. A. , Wulffraat Nico M. , Evers Andrea W. M.
Published: March 2021

Objectives

Despite the increasing knowledge about placebo effects and their beneficial impact on treatment outcomes, strategies that explicitly employ these mechanisms remain scarce. To benefit from placebo effects, it is important to gain better understanding in how individuals want to be informed about placebo effects (for example about the underlying mechanisms that steer placebo effects). The main aim of this study was to investigate placebo information strategies in a general population sample by assessing current placebo knowledge, preferences for different placebo explanations (built around well-known mechanisms involved in placebo effects), and attitudes and acceptability towards the use of placebo effects in treatment.

Design

Online survey.

Setting

Leiden, The Netherlands.

Participants

444 participants (377 completers), aged 16–78 years.

Main outcome measures

Current placebo knowledge, placebo explanation preferences, and placebo attitudes and acceptability.

Results

Participants scored high on current placebo knowledge (correct answers:M= 81.15%,SD= 12.75). Comparisons of 8 different placebo explanations revealed that participants preferred explanations based on brain mechanisms and positive expectations more than all other explanations (F(7, 368) = 3.618,p= .001). Furthermore, attitudes and acceptability for placebos in treatment varied for the type of the condition (i.e. more acceptant for psychological complaints) and participants indicated that physicians do not always have to be honest while making use of placebo effects for therapeutic benefit.

Conclusion

Our results brought forth new evidence in placebo information strategies, and indicated that explanations based on brain mechanisms and positive expectations were most preferred. These results can be insightful to construct placebo information strategies for both clinical context and research practices.
Assessment of content validity and psychometric properties of VISA-A for Achilles tendinopathy
Authors: Comins Jonathan , Siersma Volkert , Couppe Christian , Svensson Rene B. , Johansen Finn , Malmgaard-Clausen Nikolaj M. , Magnusson S. Peter
Published: March 2021

A recent COSMIN review found that the Victorian Institute of Sports Assessment–Achilles tendinopathy questionnaire (VISA-A) has flawed construct validity. The objective of the current study was to assess specifically the process of how VISA-A was constructed and validated, and whether the Danish version of VISA-A is a valid patient-reported outcome measure (PROM) for measuring the perceived impact of Achilles tendinopathy. The original item generation strategy for content validity and the process for confirming the scaling properties (construct validity) were examined. In addition, construct validity was evaluated directly using several psychometric methods (Rasch analysis, confirmatory factor analysis (CFA), and multivariable linear regression) in a cohort of 318 persons with Achilles tendinopathy with symptom duration groups ranging from less than 3 months to more than 1 year of chronicity, and a group of 120 healthy persons. We found that the item generation and item reduction in the original construction of VISA-A was based on literature review and clinician consensus with little or no patient involvement. We determined that 1) VISA-A consists of ambiguous conceptual item themes and thus lacks content validity, 2) there was no thorough investigation of the psychometric properties of the original version of VISA-A, which thus lacks construct validity, and 3) rigorous direct assessment of the psychometric properties of the Danish VISA-A revealed inadequate psychometric properties. In agreement with the COSMIN study, we conclude that when used as a single score, VISA-A is not an adequate scale for measuring self-reported impact of Achilles tendinopathy.
A genomic variant of ALPK2 is associated with increased liver fibrosis risk in HIV/HCV coinfected women
Authors: McIntosh Alec T. , Wei Renhuizi , Ahn Jaeil , Aouizerat Brad E. , Kassaye Seble G. , Augenbraun Michael H. , Price Jennifer C. , French Audrey L. , Gange Stephen J. , Anastos Kathryn M. , Goldman Radoslav
Published: March 2021

HIV coinfection is associated with more rapid liver fibrosis progression in hepatitis C (HCV) infection. Recently, much work has been done to improve outcomes of liver disease and to identify targets for pharmacological intervention in coinfected patients. In this study, we analyzed clinical data of 1,858 participants from the Women’s Interagency HIV Study (WIHS) to characterize risk factors associated with changes in the APRI and FIB-4 surrogate measurements for advanced fibrosis. We assessed 887 non-synonymous single nucleotide variants (nsSNV) in a subset of 661 coinfected participants for genetic associations with changes in liver fibrosis risk. The variants utilized produced amino acid substitutions that either altered an N-linked glycosylation (NxS/T) sequon or mapped to a gene related to glycosylation processes. Seven variants were associated with an increased likelihood of liver fibrosis. The most common variant, ALPK2 rs3809973, was associated with liver fibrosis in HIV/HCV coinfected patients; individuals homozygous for the rare C allele displayed elevated APRI (0.61, 95% CI, 0.334 to 0.875) and FIB-4 (0.74, 95% CI, 0.336 to 1.144) relative to those coinfected women without the variant. Although warranting replication, ALPK2 rs3809973 may show utility to detect individuals at increased risk for liver disease progression.
Estimating the risk of aflatoxin-induced liver cancer in Tanzania based on biomarker data
Authors: Kimanya Martin E. , Routledge Michael N. , Mpolya Emmanuel , Ezekiel Chibundu N. , Shirima Candida P. , Gong Yun Yun
Published: March 2021

Evidence about the magnitude of the aflatoxin menace can help policy makers appreciate the importance of the problem and strengthen policies to support aflatoxin mitigation measures. In this study, we estimated aflatoxin-induced liver cancer risk in 2016 for Tanzania and used the information to estimate the health burden due to the aflatoxin exposure in the country. The burden of aflatoxin-induced liver cancer was assessed based on available aflatoxin biomarker data from a previous epidemiology study, hepatitis B virus infection prevalence and population size of Tanzania in 2016. The health burden due to aflatoxin-induced liver cancer was estimated using disability adjusted life years (DALYs). The aflatoxin exposures ranged from 15.0–10,926.0 ng/kg bw/day (median, 105.5 ng/kg bw/day). We estimated that in 2016 there were about 1,480 (2.95 per 100,000 persons) new cases of aflatoxin-induced liver cancer in Tanzania and assumed all of them would die within a year. These morbidity and mortality rates led to a total loss of about 56,247.63 DALYs. These results show, quantitatively, the cases of liver cancer and related deaths that could be avoided, and the healthy life years that could be saved, annually, by strengthening measures to control aflatoxin contamination in Tanzania.
Birdsong fails to support object categorization in human infants
Authors: Woodruff Carr Kali , Perszyk Danielle R. , Waxman Sandra R.
Published: March 2021

Recent evidence reveals a precocious link between language and cognition in human infants: listening to their native language supports infants’ core cognitive processes, including object categorization, and does so in a way that other acoustic signals (e.g., time-reversed speech; sine-wave tone sequences) do not. Moreover, language is not the only signal that confers this cognitive advantage: listening to vocalizations of non-human primates also supports object categorization in 3- and 4-month-olds. Here, we move beyond primate vocalizations to clarify the breadth of acoustic signals that promote infant cognition. We ask whether listening to birdsong, another naturally produced animal vocalization, also supports object categorization in 3- and 4-month-old infants. We report that listening to zebra finch song failed to confer a cognitive advantage. This outcome brings us closer to identifying a boundary condition on the range of non-linguistic acoustic signals that initially support infant cognition.
Parent mediated intervention programmes for children and adolescents with neurodevelopmental disorders in South Asia: A systematic review
Authors: Koly Kamrun Nahar , Martin-Herz Susanne P. , Islam Md. Saimul , Sharmin Nusrat , Blencowe Hannah , Naheed Aliya
Published: March 2021

Objective

Parent-mediated programmes have been found to be cost effective for addressing the needs of the children and adolescents with Neurodevelopmental Disorders (NDD) in high-income countries. We explored the impact of parent-mediated intervention programmes in South Asia, where the burden of NDD is high.

Methods

A systematic review was conducted using the following databases; PUBMED, MEDLINE, PsycINFO, Google Scholar and Web of Science. Predefined MeSH terms were used, and articles were included if published prior to January 2020. Two independent researchers screened the articles and reviewed data.

Outcomes measures

The review included studies that targeted children and adolescents between 1 and 18 years of age diagnosed with any of four specific NDDs that are commonly reported in South Asia; Autism Spectrum Disorder (ASD), Intellectual Disability (ID), Attention Deficit Hyperactivity Disorder (ADHD) and Cerebral Palsy (CP). Studies that reported on parent or child outcomes, parent-child interaction, parent knowledge of NDDs, or child activities of daily living were included for full text review.

Results

A total of 1585 research articles were retrieved and 23 studies met inclusion criteria, including 9 Randomized Controlled Trials and 14 pre-post intervention studies. Of these, seventeen studies reported effectiveness, and six studies reported feasibility and acceptability of the parent-mediated interventions. Three studies demonstrated improved parent-child interaction, three studies demonstrated improved child communication initiations, five studies reported improved social and communication skills in children, four studies demonstrated improved parental knowledge about how to teach their children, and four studies reported improved motor and cognitive skills, social skills, language development, learning ability, or academic performance in children.

Conclusion

This systematic review of 23 studies demonstrated improvements in parent and child skills following parent-mediated intervention in South Asia. Additional evaluations of locally customized parent-mediated programmes are needed to support development of feasible interventions for South Asian countries.
Conservation genetics of the threatened plant species Physaria filiformis (Missouri bladderpod) reveals strong genetic structure and a possible cryptic species
Authors: Edwards Christine E. , Tessier Brooke C. , Swift Joel F. , Bassüner Burgund , Linan Alexander G. , Albrecht Matthew A. , Yatskievych George A.
Published: March 2021

Understanding genetic diversity and structure in a rare species is critical for prioritizing bothin situandex situconservation efforts. One such rare species isPhysaria filiformis(Brassicaceae), a threatened, winter annual plant species. The species has a naturally fragmented distribution, occupying three different soil types spread across four disjunct geographical locations in Missouri and Arkansas. The goals of this study were to understand: (1) whether factors associated with fragmentation and small population size (i.e., inbreeding, genetic drift or genetic bottlenecks) have reduced levels of genetic diversity, (2) how genetic variation is structured and which factors have influenced genetic structure, and (3) how much extant genetic variation ofP.filiformisis currently publicly protected and the implications for the development of conservation strategies to protect its genetic diversity. Using 16 microsatellite markers, we genotyped individuals from 20 populations ofP.filiformisfrom across its geographical range and one population ofPhysaria gracilisfor comparison and analyzed genetic diversity and structure. Populations ofP.filiformisshowed comparable levels of genetic diversity to its congener, except a single population in northwest Arkansas showed evidence of a genetic bottleneck and two populations in the Ouachita Mountains of Arkansas showed lower genetic variation, consistent with genetic drift. Populations showed isolation by distance, indicating that migration is geographically limited, and analyses of genetic structure grouped individuals into seven geographically structured genetic clusters, with geographic location/spatial separation showing a strong influence on genetic structure. At least one population is protected for all genetic clusters except one in north-central Arkansas, which should therefore be prioritized for protection. Populations in the Ouachita Mountains were genetically divergent from the rest ofP.filiformis; future morphological analyses are needed to identify whether it merits recognition as a new, extremely rare species.
Impact of socio-economic inequity in access to maternal health benefits in India: Evidence from Janani Suraksha Yojana using NFHS data
Authors: Mishra Prem Shankar , Veerapandian Karthick , Choudhary Prashant Kumar
Published: March 2021

Background

Caste plays a significant role in Indian society and it influences women to health care access in the community. The implementation of the maternal health benefits scheme in India is biased due to caste identity. In this context, the paper investigates access to Janani Suraksha Yojana (JSY) among social groups to establish that caste still plays a pivotal role in Indian society. Also, this paper aims to quantify the discrimination against Scheduled Castes/Scheduled Tribes (SCs/STs) in accessing JSY.

Methods

This paper uses a national-level data set of both NFHS-3 (2005–06) and NFHS-4 (2015–16). Both descriptive statistics and the Fairlie decomposition econometric model have been used to measure the explained and unexplained differences in access to JSY between SCs/STs and non-SCs/STs groups.

Results

Overall, the total coverage of JSY in India is still, 36.4%. Further, it is found that 72% of access to JSY is explained by endowment variables. The remaining unexplained percentage (28%) indicates that there is caste discrimination (inequity associated social-discrimination) against SCs/STs in access to JSY. The highest difference (54%) between SCs/STs and non-SCs/STs in access to JSY comes from the wealth quintile, with the positive sign indicating that the gap between the two social groups is widening.

Discussion and conclusion

It is necessary for the government to implement a better way to counter the caste-based discrimination in access to maternal health benefits scheme. In this regard, ASHA and Anganwadi workers must be trained to reduce the influence of dominant caste groups as well as they must be recruited from the same community to identify the right beneficiaries of JSY and in order to reduce inequity associated with social-discrimination.
A proteomics approach for the identification of cullin-9 (CUL9) related signaling pathways in induced pluripotent stem cell models
Authors: Ortolano Natalya A. , Romero-Morales Alejandra I. , Rasmussen Megan L. , Bodnya Caroline , Kline Leigh A. , Joshi Piyush , Connelly Jon P. , Rose Kristie L. , Pruett-Miller Shondra M. , Gama Vivian
Published: March 2021

CUL9 is a non-canonical and poorly characterized member of the largest family of E3 ubiquitin ligases known as the Cullin RING ligases (CRLs). Most CRLs play a critical role in developmental processes, however, the role of CUL9 in neuronal development remains elusive. We determined that deletion or depletion of CUL9 protein causes aberrant formation of neural rosettes, an in vitro model of early neuralization. In this study, we applied mass spectrometric approaches in human pluripotent stem cells (hPSCs) and neural progenitor cells (hNPCs) to identify CUL9 related signaling pathways that may contribute to this phenotype. Through LC-MS/MS analysis of immunoprecipitated endogenous CUL9, we identified several subunits of the APC/C, a major cell cycle regulator, as potential CUL9 interacting proteins. Knockdown of the APC/C adapter protein FZR1 resulted in a significant increase in CUL9 protein levels, however, CUL9 does not appear to affect protein abundance of APC/C subunits and adapters or alter cell cycle progression. Quantitative proteomic analysis of CUL9 KO hPSCs and hNPCs identified protein networks related to metabolic, ubiquitin degradation, and transcriptional regulation pathways that are disrupted by CUL9 deletion in both hPSCs. No significant changes in oxygen consumption rates or ATP production were detected in either cell type. The results of our study build on current evidence that CUL9 may have unique functions in different cell types and that compensatory mechanisms may contribute to the difficulty of identifying CUL9 substrates.
Revealing the high variability on nonconserved core and mobile elements of Austropuccinia psidii and other rust mitochondrial genomes
Authors: de Almeida Jaqueline Raquel , Riaño Pachón Diego Mauricio , Franceschini Livia Maria , dos Santos Isaneli Batista , Ferrarezi Jessica Aparecida , de Andrade Pedro Avelino Maia , Monteiro-Vitorello Claudia Barros , Labate Carlos Alberto , Quecine Maria Carolina
Published: March 2021

Mitochondrial genomes are highly conserved in many fungal groups, and they can help characterize the phylogenetic relationships and evolutionary biology of plant pathogenic fungi. Rust fungi are among the most devastating diseases for economically important crops around the world. Here, we report the complete sequence and annotation of the mitochondrial genome ofAustropuccinia psidii(syn.Puccinia psidii), the causal agent of myrtle rust. We performed a phylogenomic analysis including the complete mitochondrial sequences from other rust fungi. The genome composed of 93.299 bp has 73 predicted genes, 33 of which encoded nonconserved proteins (ncORFs), representing almost 45% of all predicted genes.A.psidiimtDNA is one of the largest rust mtDNA sequenced to date, most likely due to the abundance of ncORFs. Among them, 33% were within intronic regions of diverse intron groups. Mobile genetic elements invading intron sequences may have played significant roles in size but not shaping of the rust mitochondrial genome structure. The mtDNAs from rust fungi are highly syntenic. Phylogenetic inferences with 14 concatenated mitochondrial proteins encoded by the core genes placedA.psidiiaccording to phylogenetic analysis based on 18S rDNA. Interestingly,cox1, the gene with the greatest number of introns, provided phylogenies not congruent with the core set. For the first time, we identified the proteins encoded by threeA.psidiincORFs using proteomics analyses. Also, theorf208encoded a transmembrane protein repressed duringin vitromorphogenesis. To the best of our knowledge, we presented the first report of a complete mtDNA sequence of a member of the family Sphaerophragmiacea.
Effect of renin-angiotensin-aldosterone system inhibitors on Covid-19 patients in Korea
Authors: Park Jungchan , Lee Seung-Hwa , You Seng Chan , Kim Jinseob , Yang Kwangmo
Published: March 2021

Background

The effect of renin-angiotensin-aldosterone system (RAAS) inhibitors in coronavirus disease 19 (Covid-19) patients has not been fully investigated. We evaluated the association between RAAS inhibitor use and outcomes of Covid-19.

Methods

This study was a retrospective observational cohort study that used data based on insurance benefit claims sent to the Health Insurance Review and Assessment Service of Korea by May 15, 2020. These claims comprised all Covid-19 tested cases and the history of medical service use in these patients for the past five years. The primary outcome was all-cause mortality, and the rate of ventilator care was compared between the groups.

Results

From a total of 7,590 patients diagnosed with Covid-19, two distinct cohorts were generated based on RAAS inhibitors prescribed within 6 months before Covid-19 diagnosis. A total of 1,111 patients was prescribed RAAS inhibitors, and 794 patients were prescribed antihypertensive drugs, excluding RAAS inhibitors. In propensity-score matched analysis, 666 pairs of data set were generated, and all-cause mortality of the RAAS inhibitor group showed no significant difference compared with the non-RAAS inhibitor group (14.6% vs. 11.1%; hazard ratio [HR], 0.79; 95% confidence interval [CI], 0.54–1.15; p = 0.22). The rate of ventilator care was not significantly different between the two groups (4.4% vs. 4.1%; HR, 1.04; 95%CI, 0.60–1.79; p = 0.89).

Conclusions

RAAS inhibitor treatment did not appear to increase the mortality of Covid-19 patients compared with other antihypertensive drugs, suggesting that they may be safely continued in Covid-19 patients.
Spatiotemporal characteristics and driving forces of terrorist attacks in Belt and Road regions
Authors: Chen Lin , Mu Fengyun
Published: March 2021

To achieve the strategic goals of the Belt and Road Initiative (BRI), it is necessary to deepen our understanding of terrorist attacks in BRI countries. First, we selected data for terrorist attacks in BRI regions from 1998 to 2017 from the Global Terrorism Database and analyzed their time distribution using trend analysis and wavelet analysis. Then, we used honeycomb hexagons to present the spatial distribution characteristics. Finally, based on the Fragile States Index, we used GeoDetector to analyze the driving forces of the terrorist attacks. The following conclusions were obtained: (1) During 1998–2017, the number of events was the highest on Mondays and the lowest on Fridays. In addition, the incidence of events was high between Monday and Thursday but was the lowest on Fridays and Saturdays. The number of events was the largest in January, May, July, and November and was the lowest in June and September; the incidence of terrorist attacks from April to May and July to August was high. (2) Terrorist attacks showed a 10-year cycle during the study period. Terrorist attacks in the last 10 years of the study period were broader in scope and higher in number compared with the previous 10 years. In addition, China, Russia, Saudi Arabia, and northeastern Europe saw many new terrorist attacks during the latter 10 years. (3) The number of terrorist attacks by bombing/explosion was the largest, followed by armed attack; assassination, kidnapping, and infrastructure attacks were the least frequent. The core areas of the terrorist attacks were Iraq, Israel, Afghanistan, Pakistan, and India. (4) The driving force analysis revealed that the indicators “security apparatus,” “human flight and brain drain,” and “external intervention” contributed the most to BRI terrorist attacks.
Ecological momentary interventions for mental health: A scoping review
Authors: Balaskas Andreas , Schueller Stephen M. , Cox Anna L. , Doherty Gavin
Published: March 2021

Background

The development of mobile computing technology has enabled the delivery of psychological interventions while people go about their everyday lives. The original visions of the potential of these “ecological momentary interventions” were presented over a decade ago, and the widespread adoption of smartphones in the intervening years has led to a variety of research studies exploring the feasibility of these aspirations. However, there is a dearth of research describing the different dimensions, characteristics, and features of these interventions, as constructed.

Objective

To provide an overview of the definitions given for “ecological momentary interventions” in the treatment of common mental health disorders, and describe the set of technological and interaction possibilities which have been used in the design of these interventions.

Methods

A systematic search identified relevant literature published between 2009 and 2020 in the PubMed, PsycInfo, and ACM Guide to the Computing Literature databases. Following screening, data were extracted from eligible articles using a standardized extraction worksheet. Selected articles were then thematically categorized.

Results

The search identified 583 articles of which 64 met the inclusion criteria. The interventions target a range of mental health problems, with diverse aims, intervention designs and evaluation approaches. The studies employed a variety of features for intervention delivery, but recent research is overwhelmingly comprised of studies based on smartphone apps (30 of 42 papers that described an intervention). Twenty two studies employed sensors for the collection of data in order to provide just-in-time support or predict psychological states.

Conclusions

With the shift towards smartphone apps, the vision for EMIs has begun to be realised. Recent years have seen increased exploration of the use of sensors and machine learning, but the role of humans in the delivery of EMI is also varied. The variety of capabilities exhibited by EMIs motivates development of a more precise vocabulary for capturing both automatic and human tailoring of these interventions.
The impact of heart failure on patients and caregivers: A qualitative study
Authors: McHorney Colleen A. , Mansukhani Sonal G. , Anatchkova Milena , Taylor Natalie , Wirtz Heidi S. , Abbasi Siddique , Battle Lynwood , Desai Nihar R. , Globe Gary
Published: March 2021

Background

Heart failure is rising in prevalence but relatively little is known about the experiences and journey of patients and their caregivers. The goal of this paper is to present the symptom and symptom impact experiences of patients with heart failure and their caregivers.

Methods

This was a United States-based study wherein in-person focus groups were conducted. Groups were audio recorded, transcribed and a content-analysis approach was used to analyze the data.

Results

Ninety participants (64 patients and 26 caregivers) were included in the study. Most patients were female (52.0%) with mean age 59.3 ± 8 years; 55.6% were New York Heart Association Class II. The most commonly reported symptoms were shortness of breath (81.3%), fatigue/tiredness (76.6%), swelling of legs and ankles (57.8%), and trouble sleeping (50.0%). Patients reported reductions in social/family interactions (67.2%), dietary changes (64.1%), and difficulty walking and climbing stairs (56.3%) as the most common adverse disease impacts. Mental-health sequelae were noted as depression and sadness (43.8%), fear of dying (32.8%), and anxiety (32.8%). Caregivers (mean age 55.5 ± 11.2 years and 52.0% female) discussed 33 daily heart failure impacts, with the top three being reductions in social/family interactions (50.0%); being stressed, worried, and fearful (46.2%); and having to monitor their “patience” level (42.3%).

Conclusions

There are serious unmet needs in HF for both patients and caregivers. More research is needed to better characterize these needs and the impacts of HF along with the development and evaluation of disease management toolkits that can support patients and their caregivers.
Converting melanoma-associated fibroblasts into a tumor-suppressive phenotype by increasing intracellular Notch1 pathway activity
Authors: Shao Hongwei , Moller Mecker , Cai Long , Prokupets Rochelle , Yang Cuixia , Costa Connor , Yu Kerstin , Le Nga , Liu Zhao-Jun
Published: March 2021

Cancer-associated fibroblasts (CAFs) play a crucial role in cancer progression, drug resistance and tumor recurrence. We have recently shown that the Notch pathway determines the tumor-regulatory role of experimentally created ‘CAFs’. Here, we examined the status of Notch signaling in human melanoma-associated fibroblasts (MAFs) versus their normal counterparts and tested whether manipulation of the Notch pathway activity in MAFs alters their tumor-regulatory function. Using tissue microarrays, we found that MAFs exhibit decreased Notch pathway activity compared with normal fibroblasts in adjacent and non-adjacent skin. Consistently, MAFs isolated from human metastatic melanoma exhibited lower Notch activity than did normal human fibroblasts, demonstrating that Notch pathway activity is low in MAFs. We then investigated the effect of increasing Notch pathway activity in MAF on melanoma growth in co-cultures and in a mouse co-graft model. We found that activation of the Notch pathway in MAFs significantly restricted melanoma cell growth in vitro and suppressed melanoma skin growth and tumor angiogenesis in vivo. Our study demonstrates that the Notch signaling is inhibited in MAFs. Increase of Notch pathway activity can confer tumor-suppressive function on MAFs. Thus, targeting melanoma by activating Notch signaling in MAF may represent a novel therapeutic approach.
Open data and injuries in urban areas—A spatial analytical framework of Toronto using machine learning and spatial regressions
Authors: Vaz Eric , Cusimano Michael D. , Bação Fernando , Damásio Bruno , Penfound Elissa
Published: March 2021

Injuries have become devastating and often under-recognized public health concerns. In Canada, injuries are the leading cause of potential years of life lost before the age of 65. The geographical patterns of injury, however, are evident both over space and time, suggesting the possibility of spatial optimization of policies at the neighborhood scale to mitigate injury risk, foster prevention, and control within metropolitan regions. In this paper, Canada’s National Ambulatory Care Reporting System is used to assess unintentional and intentional injuries for Toronto between 2004 and 2010, exploring the spatial relations of injury throughout the city, together with Wellbeing Toronto data. Corroborating with these findings, spatial autocorrelations at global and local levels are performed for the reported over 1.7 million injuries. The sub-categorization for Toronto’s neighborhood further distills the most vulnerable communities throughout the city, registering a robust spatial profile throughout. Individual neighborhoods pave the need for distinct policy profiles for injury prevention. This brings one of the main novelties of this contribution. A comparison of the three regression models is carried out. The findings suggest that the performance of spatial regression models is significantly stronger, showing evidence that spatial regressions should be used for injury research. Wellbeing Toronto data performs reasonably well in assessing unintentional injuries, morbidity, and falls. Less so to understand the dynamics of intentional injuries. The results enable a framework to allow tailor-made injury prevention initiatives at the neighborhood level as a vital source for planning and participatory decision making in the medical field in developed cities such as Toronto.
Ruxolitinib with resminostat exert synergistic antitumor effects in Cutaneous T-cell Lymphoma
Authors: Karagianni Fani , Piperi Christina , Mpakou Vassiliki , Spathis Aris , Foukas Periklis G. , Dalamaga Maria , Pappa Vasiliki , Papadavid Evangelia
Published: March 2021

Background

The combination of JAK/STAT and HDAC inhibitors exerted beneficial effects in haematological malignancies, presenting promising therapeutic CTCL targets. We aim to investigate the efficacy of JAK1/2i ruxolitinib in combination with HDACi resminostat in CTCL in vitro.

Material & methods

Non-toxic concentrations of ruxolitinib and/or resminostat were administered to MyLa (MF) and SeAx (SS) cells for 24h. Cytotoxicity, cell proliferation and apoptosis were estimated through MTT, BrdU/7AAD and Annexin V/PI assay. Multi-pathway analysis was performed to investigate the effect of JAK1/2i and/or HDACi on JAK/STAT, Akt/mTOR and MAPK signalling pathways.

Results

Both drugs and their combination were cytotoxic in MyLa (p<0.05) and in SeAx cell line (p<0.001), inhibited proliferation of MyLa (p<0.001) and SeAx (p<0.001) at 24h, compared to untreated cells. Moreover, combined drug treatment induced apoptosis after 24h (p<0.001) in MyLa, and SeAx (p<0.001). The combination of drugs had a strong synergistic effect with a CI<1. Importantly, the drugs’ combination inhibited phosphorylation of STAT3 (p<0.001), Akt (p<0.05), ERK1/2 (p<0.001) and JNK (p<0.001) in MyLa, while it reduced activation of Akt (p<0.05) and JNK (p<0.001) in SeAx.

Conclusion

The JAKi/HDACi combination exhibited substantial anti-tumor effects in CTCL cell lines, and may represent a promising novel therapeutic modality for CTCL patients.
Using RE-AIM to examine the potential public health impact of an integrated collaborative care intervention for weight and depression management in primary care: Results from the RAINBOW trial
Authors: Lewis Megan A. , Wagner Laura K. , Rosas Lisa G. , Lv Nan , Venditti Elizabeth M. , Steinman Lesley E. , Weiner Bryan J. , Goldhaber-Fiebert Jeremy D. , Snowden Mark B. , Ma Jun
Published: March 2021

Background

An integrated collaborative care intervention was used to treat primary care patients with comorbid obesity and depression in a randomized clinical trial. To increase wider uptake and dissemination, information is needed on translational potential.

Methods

The trial collected longitudinal, qualitative data at baseline, 6 months (end of intensive treatment), 12 months (end of maintenance treatment), and 24 months (end of follow-up). Semi-structured interviews (n = 142) were conducted with 54 out of 409 randomly selected trial participants and 37 other stakeholders, such as recruitment staff, intervention staff, and clinicians. Using a Framework Analysis approach, we examined themes across time and stakeholder groups according to the RE-AIM (Reach, Effectiveness, Adoption, Implementation, and Maintenance) framework.

Results

At baseline, participants and other stakeholders reported being skeptical of the collaborative care approach related to some RE-AIM dimensions. However, over time they indicated greater confidence regarding the potential for future public health impact. They also provided information on barriers and actionable information to enhance program reach, effectiveness, adoption, implementation, and maintenance.

Conclusions

RE-AIM provided a useful framework for understanding how to increase the impact of a collaborative and integrative approach for treating comorbid obesity and depression. It also demonstrates the utility of using the framework as a planning tool early in the evidence-generation pipeline.
Effect of conditional deletion of cytoplasmic dynein heavy chain DYNC1H1 on postnatal photoreceptors
Authors: Dahl Tiffanie M. , Reed Michelle , Gerstner Cecilia D. , Ying Guoxin , Baehr Wolfgang
Published: March 2021

Cytoplasmic dynein (dynein 1), a major retrograde motor of eukaryotic cells, is a 1.4 MDa protein complex consisting of a pair of heavy chains (DYNC1H1) and a set of heterodimeric noncatalytic accessory components termed intermediate, light intermediate and light chains. DYNC1H1 (4644 amino acids) is the dynein backbone encoded by a gene consisting of 77 exons. We generated a floxed Dync1h1 allele that excises exons 24 and 25 and truncates DYNC1H1 during Six3Cre-induced homologous recombination. Truncation results in loss of the motor and microtubule-binding domain. Dync1h1F/F;Six3Cre photoreceptors degenerated rapidly within two postnatal weeks. In the postnatal day 6 (P6) Dync1h1F/F;Six3Cre central retina, outer and inner nuclear layers were severely disorganized and lacked a recognizable outer plexiform layer (OPL). Although the gene was effectively silenced by P6, DYNC1H1 remnants persisted and aggregated together with rhodopsin, PDE6 and centrin-2-positive centrosomes in the outer nuclear layer. As photoreceptor degeneration is delayed in the Dync1h1F/F;Six3Cre retina periphery, retinal lamination and outer segment elongation are in part preserved. DYNC1H1 strongly persisted in the inner plexiform layer (IPL) beyond P16 suggesting lack of clearance of the DYNC1H1 polypeptide. This persistence of DYNC1H1 allows horizontal, rod bipolar, amacrine and ganglion cells to survive past P12. The results show that cytoplasmic dynein is essential for retina lamination, nuclear positioning, vesicular trafficking of photoreceptor membrane proteins and inner/outer segment elaboration.
Minimally invasive versus open radical resection surgery for hilar cholangiocarcinoma: Comparable outcomes associated with advantages of minimal invasiveness
Authors: Tang Wei , Qiu Jian-Guo , Deng Xin , Liu Shan-Shan , Cheng Luo , Liu Jia-Rui , Du Cheng-You
Published: March 2021

Background

Minimally invasive surgery (MIS) provides a new approach for patients with hilar cholangiocarcinoma (HCCA). However, whether it can achieve similar outcomes to traditional open surgery (OS) remains controversial.

Methods

To assess the safety and feasibility of MIS for HCCA, a systematic review and meta-analysis was performed to compare the outcomes of MIS with OS. Seventeen outcomes were assessed.

Results

Nine studies involving 382 patients were included. MIS was comparable in blood transfusion rate, R0 resection rate, lymph nodes received, overall morbidity, severe morbidity (Clavien–Dindo classification > = 3), bile leakage rate, wound infection rate, intra-abdominal infection rate, days until oral feeding, 1-year overall survival, 2-year overall survival and postoperative mortality with OS. Although operation time was longer (mean difference (MD) = 93.51, 95% confidence interval (CI) = 64.10 to 122.91, P < 0.00001) and hospital cost (MD = 0.68, 95% CI = 0.03 to 1.33, P = 0.04) was higher in MIS, MIS was associated with advantages of minimal invasiveness, that was less blood loss (MD = -81.85, 95% CI = -92.09 to -71.62, P < 0.00001), less postoperative pain (MD = -1.21, 95% CI = -1.63 to -0.79, P < 0.00001), and shorter hospital stay (MD = -4.22, 95% CI = -5.65 to -2.80, P < 0.00001).

Conclusions

The safety and feasibility of MIS for HCCA is acceptable in selected patients. MIS is a remarkable alternative to OS for providing comparable outcomes associated with a benefit of minimal invasiveness and its application should be considered more.
A view from China: Reflecting back on James Elkins’ Chinese Landscape Painting
Authors: Yingchun Zang
Published: March 2021

In this article, the author, a scholar based in China, reflects on James Elkins’ book Chinese Landscape Painting. She notes that the development of Chinese art has a complete history. As a cultural system that has grown and developed in a long and relatively isolated state, it has formed a unique philosophical aesthetic thought and a unique form of artistic expression. Chinese landscape painting is a part of this complex and rich cultural system, and it would be meaningless to discuss Chinese landscape painting in isolation from this ever-changing cultural ecology.
Noi credevamo (We Believed): Story and history of emotions
Authors: Patat Alejandro
Published: March 2021

In the last ten years, Noi credevamo (We Believed) () has been the subject of a very careful criticism interested not only in its historical-ideological implications but also in its semiotic specificities. The purpose of this article is to summarize the cardinal points of these two positions and to add to them some critical observations that have not been noted so far. On the one hand, it is a matter of highlighting how, as a historical film, the work is connected with the history of emotions, a recent historiographical trend that aims to detect the narrative devices of ideological propaganda and the diffusion of feelings since the late eighteenth century. On the other hand, the article proposes a new interpretation of Mario Martone’s film, starting with the analysis of phenomena that are not only historical but also technical and structural.
Zavattini: Il Neo-Realismo e il Nuovo Cinema Latino-americano Volumi I–II, David Brancaleone (2019)
Authors: Valecce Anastasia
Published: March 2021

Review of: Zavattini: Il Neo-Realismo e il Nuovo Cinema Latino-americano Volumi I–II, David Brancaleone (2019)

Vol. I, Parma: Diabasis, 486 pp.,

ISBN 978-8-88103-935-7, p/bk, €24.00

Vol. II, Parma: Diabasis 794 pp.,

ISBN 978-8-88103-937-1, e-book, free
Indro Montanelli e il cinema: Un contadino toscano candidato all’Oscar, Rinaldo Vignati (2019)
Authors: Leavitt Charles L.
Published: March 2021

Review of: Indro Montanelli e il cinema: Un contadino toscano candidato all’Oscar, Rinaldo Vignati (2019)

Milan and Udine: Mimesis Edizioni, 264 pp.,

ISBN 978-8-85755-616-1, p/bk, €22.00
Lourenço Marques and Lisbon in João Albasini’s chronicles
Authors: Falconi Jessica
Published: March 2021

The Mozambique-born journalist João dos Santos Albasini (1876–1922) is one of the most well-known names of the colonial periodical press of the Portuguese Empire. Furthermore, he is often mentioned in historiographical accounts on the birth and development of literary culture in colonial Mozambique. Albasini lived during the period of development of the port facilities in Lourenço Marques and as it underwent deep transformations in its social relations. As a main project of the capital city’s growth, the development of the port and the railways dominated urban life and the landscape, which is reflected peculiarly in Albasini’s life and writing. This article is a case study of the relationship between the colonial periodical press and port cities through analyses of a selection of his chronicles published in the newspapers O Africano (The African) (1908–18) and O Brado Africano (The African Cry) (1918–75).
From Lisbon to Macau: The conquest of the air as seen by the Portuguese press in a comparative approach1
Authors: Costa Cátia Miriam , Pestana Olívia
Published: March 2021

In 1924, two well-known Portuguese servicemen made the first flight between Lisbon and Macau. The press of the time not only followed this adventure but also supported it, playing an active role as it unfolded. This article presents a comparison of the content of news published in two Portuguese newspapers, the Diário de Lisboa and Comércio do Porto, one based in Lisbon and the other in Porto, between 1 April and 30 June that year, the period during which the trip took place. The aim is to analyse the involvement of these periodicals in this project, which assumes journalistic characteristics, but also their commitment to raise funds and their role in the mobilization of the public and as intermediaries between the pilots and public authorities.
Corruption and economic competitiveness: What Greece can tell us
Authors: Rontos Kostas , Syrmali Maria-Eleni , Vavouras Ioannis , Salvati Luca
Published: March 2021

Under the assumption that economic competitiveness has a significant impact on the overall level of corruption in a given country, the present study evaluates the influence that a wide array of national reforms related to the pillars of structural competitiveness has on corruption in the case of Greece. In order to inform national and regional policies against corruption, three indices were calculated that express: (1) the impact of each specific reform on corruption; (2) the required reform effort and (3) the efficiency of the reform index, taking into consideration the competitiveness gap between Greece and Switzerland – the country with the best performance worldwide in terms of competitiveness. These indicators may indicate which reforms have the highest payoff in terms of corruption abatement, which are less costly to undertake and which deliver the greatest reduction in corruption per required effort, respectively. The empirical results of this study suggest that in a number of areas the associated reforms may translate into lower levels of corruption. Under this conceptual framework, institutions seem to be of high importance as they have a substantial impact as far as the reduction of corruption is concerned, with relatively low reform effort. Therefore, a comprehensive policy reform referring to the pillars of structural competitiveness is expected to deliver lower levels of corruption in Greece, allowing the substantial increase of its competitiveness and hence its faster convergence with the more advanced economies in the European Union.
Trauma expressed pathologically: Unpacking the use of tuberculosis as a metaphor in Ritwik Ghatak’s Meghe Dhaka Tara
Authors: Gupta Neha
Published: March 2021

In this article, I unravel the use of tuberculosis as a metaphor in Ritwik Ghatak's Meghe Dhaka Tara (The Cloud-Capped Star), and locate it within the indices of loss Ghatak uses in the film to designate the tragic and brutal partition of the Bengal Presidency in 1947. Nita’s illness – which was both her tragedy and salvation – had to be a careful selection; it had to be semiotically proximate to the other meanings and metaphors imputed to Nita. To establish the salience of the use of tuberculosis, I underscore the link between the perception of tuberculosis and the ‘being’ of the protagonist (Nita) it sublimates. I further demonstrate that tuberculosis is the most apt disease, because the metaphors that the disease has been imbued with assimilate into the larger symbolic register that Ghatak uses in the film. I posit that Nita – ‘also’, and perhaps more acutely – suffers from the imperatives of tuberculosis – the characteristics associated with the disease in the popular imagination – rather than the mere pathological condition caused by the pathogen, mycobacterium tuberculosis.