bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisions of clinical protocols using the Plan Do Check Act cycle improved outcomes of extremely preterm infants at 2 years
Authors: Saikusa Mamoru , Kinoshita Masahiro , Tsuda Kennosuke , Hisano Tadashi , Okada Junichiro , Iwata Sachiko , Fujino Hiroshi , Maeno Yasuki , Yamashita Yushiro , Iwata Osuke
Published: March 2021

Aim

Clinical quality improvement is often cumbersome due to established protocols. We aimed to investigate whether outcomes of preterm infants improve with protocol revisions using iteration cycles.

Methods

Preterm infants born <28 weeks gestation between January 2006 and December 2015 were retrospectively analysed. Protocols were revised using Plan Do Check Act cycle. Death and serious adverse events at term were reviewed in six‐monthly quality improvement meetings. Adverse outcome of death or motor/sensory impairments at two years was compared before and after two major protocol changes, which were implemented in January 2008 and January 2012.

Results

Based on the appraisal for period 2006–2007, strategies for surfactant, narcotics, parenteral nutrition, respiratory gas humidity and prophylactic indomethacin and antibiotics were changed for period 2008–2011. For period 2012–2015, stabilisation of infants was accelerated via very early catheterisation. Of 162 infants (84 males, 25.5 ± 1.5 weeks gestation) within the whole cohort, 63 developed adverse outcomes, which were fewer for periods 2008–2011 (p = 0.013) and 2012–2015 (p = 0.035) compared with period 2006–2007 (adjusted for gestational age, Apgar scores and sex).

Conclusion

Careful bottom‐up revisions of protocols using iteration cycles, accounting for local settings, successfully improved the outcomes of preterm infants.
‘We don't know what tomorrow will bring’: Parents' experiences of caring for a child with an undiagnosed genetic condition
Authors: Aldiss Susie , Gibson Faith , Geoghegan Sophie , Jewitt Anna , Elliott Tara Kerr , Williams Anna , Wray Jo , Oulton Kate
Published: March 2021

Background

Families and healthcare professionals caring for a sick or disabled child without a definitive diagnosis face unique challenges, particularly in relation to managing uncertainty, access to healthcare and coordination of care. There has been little research exploring the impact this has on families, their support needs or their experience of health services.

Methods

This qualitative interview study included interviews with 14 mothers of children with undiagnosed genetic conditions. Transcripts were analysed using thematic analysis.

Results

Four themes emerged, uncovering overlapping patterns in the data: (1) living with complexity amidst uncertainty—‘We don't know what tomorrow will bring’; (2) parental role—‘I do everything I can’; (3) parental role—‘Not coping is not an option’; and (4) support needs—‘There's lots of help that just isn't out there’.

Conclusions

The results clearly demonstrate the stresses faced when caring for a child with an undiagnosed genetic condition. Some themes are shared with the experience of other families caring for children with complex needs. However, parents were doing all they could for their child in the context of a life of uncertainty, with the absence of a clear diagnosis clearly causing additional stress that impacted on the whole family. Impact on their emotional and physical well‐being was evident; they described times of feeling stressed, worried and anxious. They were confused due to being overloaded with information and frustrated by a lack of care coordination. Parents did not appear to prioritize their own well‐being and held back their emotions to protect themselves and others. As a result, they had many unmet needs, particularly relating to emotional support.
Neuroimmunology in neurological and psychiatric disorders
Authors: Takeuchi Hideyuki
Published: March 2021

The central nervous system (CNS) has long been considered as an immunological privileged site where the surveillance of the immune system does not reach out. However, it is now recognized that this CNS homeostasis is collapsed by neuroinflammation such as influx of proinflammatory factors and cells, neuronal dysfunction, and glial activation. Currently, CNS neuroinflammation is considered as a main pathomechanism to mediate disease progression in not only neurotrauma and neuroinflammatory disorders but also neurodegenerative diseases including dementia. Moreover, growing evidence indicates that chronic CNS neuroinflammation is also involved in the pathogenesis of psychiatric disorders such as autism spectrum disorders, depression, and schizophrenia. This paper reviews the current proposed pathomechanisms and therapeutic strategies of neurological and psychiatric disorders from a point of view of chronic neuroinflammation.
Transfer Deep Learning for Reconfigurable Snapshot HDR Imaging Using Coded Masks
Authors: Alghamdi Masheal , Fu Qiang , Thabet Ali , Heidrich Wolfgang
Published: March 2021

High dynamic range (HDR) image acquisition from a single image capture, also known as snapshot HDR imaging, is challenging because the bit depths of camera sensors are far from sufficient to cover the full dynamic range of the scene. Existing HDR techniques focus either on algorithmic reconstruction or hardware modification to extend the dynamic range. In this paper we propose a joint design for snapshot HDR imaging by devising a spatially varying modulation mask in the hardware and building a deep learning algorithm to reconstruct the HDR image. We leverage transfer learning to overcome the lack of sufficiently large HDR datasets available. We show how transferring from a different large‐scale task (image classification on ImageNet) leads to considerable improvements in HDR reconstruction. We achieve a reconfigurable HDR camera design that does not require custom sensors, and instead can be reconfigured between HDR and conventional mode with very simple calibration steps. We demonstrate that the proposed hardware–software so lution offers a flexible yet robust way to modulate per‐pixel exposures, and the network requires little knowledge of the hardware to faithfully reconstruct the HDR image. Comparison results show that our method outperforms the state of the art in terms of visual perception quality.
Preoperative weight loss in women with obesity in gynaecologic oncology: A retrospective study
Authors: Aubrey Christa , Skeldon Matthew , Chapelsky Sarah , Giannakopoulos Nadia , Ghosh Sunita , Steed Helen , Pin Sophia
Published: March 2021

To retrospectively review the efficacy of short term supervised medical weight loss for women with obesity, body mass index (BMI ≥40 kg/m2) in gynaecologic oncology, and the associated perioperative and pathologic outcomes. A retrospective study of a dedicated preoperative weight loss clinic for gynaecologic oncology patients from March to December 2019. Statistical analysis was performed with McNemar's test for correlated proportions, Pearson's correlation tests for continuous variables, and paired t‐tests to compare means. Generalized estimating equations (GEE) were used to determine the factors associated with weight loss over time. A P‐value of <.05 was used for statistical significance. Review of cases up‐graded after surgery was performed by a gynaecologic pathologist. There were a total of 49 women included in the study. The most common referral reason was endometrioid carcinoma or hyperplasia of the endometrium (77.6%). Mean initial weight was 130.2 kg, and corresponding mean BMI 48.1 kg/m2. Patients attended on average nine preoperative weight loss visits. A significant difference between initial weight and weight at surgery was demonstrated, from 129.6 to 118.0 kg (8.4% weight loss) (P < .0001). This difference persisted to their post‐surgical visit, with an additional mean loss of 1.89 kg (9.4% weight loss) (P = .044). The majority (92.1%) of patients with endometrial pathology had surgical management, and of these 85.7% were minimally invasive. Preoperative weight loss is a feasible option in gynaecologic oncology patients. Greater understanding of clinical significance, follow‐up, and ideal target population for this intervention is needed.
Drought, fire and grazing precursors to large‐scale pine forest decline
Authors: Connor Simon E. , Araújo João , Boski Tomasz , Gomes Ana , Gomes Sandra D. , Leira Manel , Freitas Maria da Conceição , Andrade Cesar , Morales‐Molino César , Franco‐Múgica Fátima , Akindola Rufus B. , Vannière Boris
Published: March 2021

Aim

Temperate forests are currently facing multiple stresses due to climate change, biological invasions, habitat fragmentation and fire regime change. How these stressors interact with each other influences how, when and whether ecosystems recover, or whether they adapt or transition to a different ecological state. Because forest recovery or collapse may take longer than a human lifetime, predicting the outcomes of different stressor combinations remains difficult. A clearer vision of future forest trajectories in a changing world may be gained by examining collapses of forests in the past. Here, we use long‐term ecological data to conduct a post‐mortem examination of the decline of maritime pine forests (Pinus pinaster Ait.) on the SW Iberian Peninsula 7000–6500 years ago.

Location

Portugal and Spain.

Methods

We compared four palaeoecological records—two with pine declines and two without—using a multiproxy approach. Bioclimatic differences between the four sites were explored. Proxies for past vegetation and disturbance (fire and grazing) were compared with independent palaeoclimatic records. We performed functional traits analysis and used phase plots to examine the causes of pine decline.

Results

The pine decline represents a critical transition in SW Iberia, which lies close to maritime pine's bioclimatic limits. Prolonged drought likely killed trees and suppressed the fires that normally stimulate pine germination and pinewood recovery. Increased grazing pressure facilitated the rapid spread of resprouter shrubs. These competed with pine trees and ultimately replaced them. Our data highlight complex interactions between climate, fire, grazing and forest resilience.

Main Conclusions

The pine decline occurred at least a century after post‐fire resprouters overtook obligate seeders in the vegetation, constituting an early‐warning signal of forest loss. Fire suppression, resprouter encroachment and grazing may threaten the persistence of Mediterranean forests as droughts become more frequent and extreme.
Metformin and health outcomes: An umbrella review of systematic reviews with meta‐analyses
Authors: Li Xue , Celotto Stefano , Pizzol Damiano , Gasevic Danijela , Ji Meng‐Meng , Barnini Tommaso , Solmi Marco , Stubbs Brendon , Smith Lee , López Sánchez Guillermo F. , Pesolillo Gabriella , Yu Zengli , Tzoulaki Ioanna , Theodoratou Evropi , Ioannidis John P.A. , Veronese Nicola , Demurtas Jacopo
Published: March 2021

Background

The objective was to capture the breadth of outcomes that have been associated with metformin use and to systematically assess the quality, strength and credibility of these associations using the umbrella review methodology.

Methods

Four major databases were searched until 31 May 2020. Meta‐analyses of observational studies and meta‐analyses of randomized controlled trials (RCTs) (including active and placebo control arms) were included.

Results

From 175 eligible publications, we identified 427 different meta‐analyses, including 167 meta‐analyses of observational studies, 147 meta‐analyses of RCTs for metformin vs placebo/no treatment and 113 meta‐analyses of RCTs for metformin vs active medications. There was no association classified as convincing or highly suggestive from meta‐analyses of observational studies, but some suggestive/weak associations of metformin use with a lower mortality risk of CVD and cancer. In meta‐analyses of RCTs, metformin was associated with a lower incidence of diabetes in people with prediabetes or no diabetes at baseline; lower ovarian hyperstimulation syndrome incidence (in women in controlled ovarian stimulation); higher success for clinical pregnancy rate in poly‐cystic ovary syndrome (PCOS); and significant reduction in body mass index in people with type 1 diabetes mellitus, in women who have obesity/overweight with PCOS and in obese/overweight women. Of 175 publications, 166 scored as low or critically low quality per AMSTAR 2 criteria.

Conclusions

Observational evidence on metformin seems largely unreliable. Randomized evidence shows benefits for preventing diabetes and in some gynaecological and obstetrical settings. However, almost all meta‐analyses are of low or critically low quality according to AMSTAR 2 criteria.
Trophic ecology of the arboreal and ground ant communities in forests and savannas of central Brazil
Authors: Vieira Jésica , Camarota Flávio , Vasconcelos Heraldo L.
Published: March 2021

1. The trophic ecology of organisms is often mediated by habitat characteristics. Ants are key organisms of most food webs, and their diet can be plastic depending on the relative availability of different nutrients.

2. Using stable isotope analysis, we investigated whether there were differences in the trophic position (δ15N) and/or in the relative importance of different carbon sources (δ13C) between the arboreal and ground‐dwelling ant communities inhabiting two adjacent and contrasting habitats (savannas and semideciduous forests).

3. Arboreal species on average occupied lower trophic positions (lower δ15N) than did the ground‐dwelling species, as probably in the arboreal stratum there is a prevalence of genera whose species rely heavily on plant and insect exudates. However, regardless of the foraging/nesting strata, there was no difference in mean δ15N between the savanna and forest communities, indicating that differences between these two habitats in the relative availability of sources of protein and carbohydrates for ants are either small or non‐significant.

4. The savanna ant community presented a greater δ13C than did the forest community, as expected, given the high abundance of C4 grasses in savannas. However, the difference in δ13C between the two communities was relatively small, as few savanna species derived most of their carbon from C4‐based food webs.

5. Overall, our study provided important insights into the trophic ecology of ant communities inhabiting contrasting natural habitats, such as different vegetation strata and adjacent forests and savannas.
High‐fat diet during adulthood interacts with prenatal stress, affecting both brain inflammatory and neuroendocrine markers in male rats
Authors: Berry Alessandra , Mazzelli Monica , Musillo Chiara , Riva Marco Andrea , Cattaneo Annamaria , Cirulli Francesca
Published: March 2021

Prenatal stress (PNS) affects foetal programming and, through an interaction with subsequent challenges, can increase vulnerability to mood and metabolic disorders. We have previously shown that, following PNS, adult male rats are characterized by increased vulnerability to a metabolic stressor experienced at adulthood (8‐week‐high‐fat diet—HFD). In this study, we specifically assessed whether PNS might interact with an adult metabolic challenge to induce an inflammatory phenotype. Changes in the expression levels of inflammatory (Il‐1β, Tnf‐α, Il‐6) and of stress response mediators (Nr3c1, Fkbp5) as well as of mood and metabolic regulators (Bdnf, Ghs‐R) were investigated in the hippocampus, prefrontal cortex and hypothalamus, brain regions involved in the pathogenesis of depression and prone to inflammation in response to stress. Overall, PNS reduced the expression of Bdnf and Tnf‐α, while HFD administered at adulthood counteracted this effect suggesting that PNS impinges upon the same pathways regulating responses to a metabolic challenge at adulthood. Furthermore, HFD and PNS affected the expression of both Nr3c1 and Fkbp5, two neuroendocrine mediators involved in the response to stress, metabolic challenges and in the modulation of the emotional profile (as shown by the correlation between Fkbp5 and the time spent in the open arms of the elevated plus‐maze). Overall, these results indicate that the same metabolic and neuroendocrine effectors engaged by PNS are affected by metabolic challenges at adulthood, providing some mechanistic insight into the well‐known comorbidity between mood and metabolic disorders.
Not that clean: Aquaculture‐mediated translocation of cleaner fish has led to hybridization on the northern edge of the species' range
Authors: Faust Ellika , Jansson Eeva , André Carl , Halvorsen Kim Tallaksen , Dahle Geir , Knutsen Halvor , Quintela María , Glover Kevin A.
Published: March 2021

Translocation and introduction of non‐native organisms can have major impacts on local populations and ecosystems. Nevertheless, translocations are common practices in agri‐ and aquaculture. Each year, millions of wild‐caught wrasses are transported large distances to be used as cleaner fish for parasite control in marine salmon farms. Recently, it was documented that translocated cleaner fish are able to escape and reproduce with local wild populations. This is especially a challenge in Norway, which is the world's largest salmon producer. Here, a panel of 84 informative SNPs was developed to identify the presence of nonlocal corkwing wrasse (Symphodus melops) escapees and admixed individuals in wild populations in western Norway. Applying this panel to ~2000 individuals, escapees and hybrids were found to constitute up to 20% of the local population at the northern edge of the species’ distribution. The introduction of southern genetic material at the northern edge of the species distribution range has altered the local genetic composition and could obstruct local adaptation and further range expansion. Surprisingly, in other parts of the species distribution where salmon farming is also common, few escapees and hybrids were found. Why hybridization seems to be common only in the far north is discussed in the context of demographic and transport history. However, the current lack of reporting of escapes makes it difficult to evaluate possible causes for why some aquaculture‐dense areas have more escapees and hybrids than others. The results obtained in this study, and the observed high genomic divergence between the main export and import regions, puts the sustainability of mass translocation of nonlocal wild wrasse into question and suggests that the current management regime needs re‐evaluation.
Phenological stage of tundra vegetation controls bidirectional exchange of BVOCs in a climate change experiment on a subarctic heath
Authors: Baggesen Nanna , Li Tao , Seco Roger , Holst Thomas , Michelsen Anders , Rinnan Riikka
Published: March 2021

Traditionally, biogenic volatile organic compound (BVOC) emissions are often considered a unidirectional flux, from the ecosystem to the atmosphere, but recent studies clearly show the potential for bidirectional exchange. Here we aimed to investigate how warming and leaf litter addition affect the bidirectional exchange (flux) of BVOCs in a long‐term field experiment in the Subarctic. We also assessed changes in net BVOC fluxes in relation to the time of day and the influence of different plant phenological stages. The study was conducted in a full factorial experiment with open top chamber warming and annual litter addition treatments in a tundra heath in Abisko, Northern Sweden. After 18 years of treatments, ecosystem‐level net BVOC fluxes were measured in the experimental plots using proton‐transfer‐reaction time‐of‐flight mass spectrometry (PTR–ToF–MS). The warming treatment increased monoterpene and isoprene emissions by ≈50%. Increasing temperature, due to diurnal variations, can both increase BVOC emission and simultaneously, increase ecosystem uptake. For any given treatment, monoterpene, isoprene, and acetone emissions also increased with increasing ambient air temperatures caused by diurnal variability. Acetaldehyde, methanol, and sesquiterpenes decreased likely due to a deposition flux. For litter addition, only a significant indirect effect on isoprene and monoterpene fluxes (decrease by ~50%–75%) was observed. Litter addition may change soil moisture conditions, leading to changes in plant species composition and biomass, which could subsequently result in changes to BVOC emission compositions. Phenological stages significantly affected fluxes of methanol, isoprene and monoterpenes. We suggest that plant phenological stages differ in impacts on BVOC net emissions, but ambient air temperature and photosynthetically active radiation (PAR) also interact and influence BVOC net emissions differently. Our results may also suggest that BVOC fluxes are not only a response to changes in temperature and light intensity, as the circadian clock also affects emission rates.
Investigating the vascularization capacity of a decellularized dental pulp matrix seeded with human dental pulp stem cells: in vitro and preliminary in vivo evaluations
Authors: Alghutaimel H. , Yang X. , Drummond B. , Nazzal H. , Duggal M. , Raïf E.
Published: March 2021

Aim

To investigate the vascularization capacity of a decellularized dental pulp matrix (DDP) of bovine origin seeded with human dental pulp stem cells (hDPSCs) in vitro and to present preliminary in vivo findings.

Methodology

Bovine dental pulps were decellularized and then analysed using histological staining and DNA quantification. The resultant DDPs were characterized using immunohistochemical staining for the retention of vascular endothelial growth factor A (VEGF‐A) and fibroblast growth factor 2 (FGF‐2). Furthermore, DDPs were recellularized with hDPSCs and analysed histologically. The expression of markers involved in angiogenesis by hDPSCs colonizing the DDPs was assessed in vitro. A preliminary in vivo study was then conducted in which hDPSCs‐seeded and unseeded DDPs were inserted in debrided human premolars root slices and implanted subcutaneously in immunodeficient mice. Samples were retrieved after 30 days and analysed using histological and immunohistochemical staining. The independent samples t‐test, analysis of variance and a Kruskal–Wallis test were used to analyse the quantitative data statistically depending on the group numbers and normality of data distribution. The difference between the groups was considered significant when the P‐value was less than 0.05.

Results

Acellular dental pulp matrices were generated following bovine dental pulp decellularization. Evaluation of the developed DDPs revealed a significant DNA reduction (P < 0.0001) with preservation of the native histoarchitecture and vasculature and retention of VEGF‐A and FGF‐2. Upon recellularization of the DDPs with hDPSCs, the in vitro analyses revealed cell engraftment with progressive repopulation of DDPs’ matrices and vasculature and with enhanced expression of markers involved in angiogenesis. In vivo implantation of root slices with hDPSCs‐seeded DDPs revealed apparent vascularization enhancement as compared to the unseeded DDP group (P < 0.0001).

Conclusions

The developed decellularized dental pulp matrix had pro‐angiogenic properties characterized by the retention of native vasculature and angiogenic growth factors. Seeding of hDPSCs into the DDP led to progressive repopulation of the vasculature, enhanced expression of markers involved in angiogenesis in hDPSCs and improved in vivo vascularization capacity. The se suggest that a combination of DDP and hDPSCs have the potential to provide a promising vascularization promoting strategy for dental pulp regeneration.
Changes in liver fibrosis in patients with chronic hepatitis C after successful direct‐acting antiviral therapy
Authors: Sadeghi Anahita , Amiri Roya , Akbarpour Elham , Mirminachi Babak , Sharifi Amir‐Houshang , Merat Shahin
Published: March 2021

Introduction and Objectives

After successful treatment of hepatitis C virus (HCV) infection with direct‐acting antivirals (DAAs), the stage of liver fibrosis decreases over time. Here, we aimed to assess the changes in the liver fibrosis stage using transient elastography (TE) after successful DAA therapy in HCV‐infected cirrhotic patients who were referred to Shariati hospital from 2016 to 2017.

Material and Methods

In this observational cohort, all HCV‐infected cirrhotic patients who were treated with a combination of sofosbuvir/daclatasvir, had sustained virologic response (SVR), and had undergone pre‐ and post‐treatment TE, were enrolled. The primary outcome was the changes in TE parameters six months after the end of treatment compared with baseline.

Results

A total of 442 eligible subjects received DAA therapy. Overall, the SVR rate was 96.6%. Of these, 149 patients had completed the protocol and were enrolled. The mean age of patients was 56.1 ± 10.3 years and the predominant sex was male (77.9%). The median (Q1‐Q3) liver stiffness (LS) value at baseline was 26.3 kPa (18.1‐38 kPa), which significantly decreased to 20.9 kPa (12‐29.7 kPa) [z = −8.45, P‐value < .001]. Also, the liver steatosis of patients with baseline CAP ≥ 220 dB/m had a significant response to treatment [z = −2.3, P‐value = .023]. Based on multivariate analysis, a higher baseline liver fibrosis stage was the only determinant of LS values improvement in our study.

Conclusion

Successful HCV eradication in patients with liver fibrosis results in significant improvement in LS, even in cirrhotic patients.
Biogeography of Neotropical mastiff bats: A case of multiple dispersals between the Caribbean and mainland
Authors: Loureiro Livia O. , Engstrom Mark D. , Lim Burton K.
Published: March 2021

Aim

Bats are the only group of mammals with extant native species present throughout the islands of the Antilles, Central America, and South America. Here, we test competing hypotheses of species diversification in mastiff bats and deepen our understanding of the dominant biogeographical processes involved in evolution and distribution in the Neotropics. We estimated the number of dispersals between the major geographic areas and whether vicariant events, such as the Andean uplift in the Miocene/Pliocene and Pleistocene glaciations, disrupted gene flow.

Location

South America, Central America, and Caribbean.

Taxon

Molossus, Neotropical mastiff bats.

Methods

We used the phylogeny derived from a Genotype by Sequencing approach to test different biogeographical models in the Neotropics. Bayesian inference with molecular and geological calibration points was also used to estimate the age of major lineage divergences withinMolossusand to infer speciation events.

Results

Most diversification withinMolossusoccurred relatively recently and over a short period of time during the Pleistocene. The best‐fit model, dispersal‐extinction cladogenesis, showed that anagenetic dispersal, sympatric speciation, and vicariance all appear to have been involved in the evolutionary history of the Neotropics. Divergence times suggest that geological and paleo‐climatic events were important factors inMolossusdiversification.

Main conclusions

Pleistocene refugia in South America and the formation of the Panama Isthmus are likely to have played an important role in speciation withinMolossus, while the Caribbean species are the result of at least two independent dispersal events to the archipelago from South America and Central America, coinciding with low sea levels during the Pleistocene.
Nemolizumab is associated with a rapid improvement in atopic dermatitis signs and symptoms: subpopulation (EASI ≥ 16) analysis of randomized phase 2B study
Authors: Silverberg J.I. , Pinter A. , Alavi A. , Lynde C. , Bouaziz J.‐D. , Wollenberg A. , Murrell D.F. , Alpizar S. , Laquer V. , Chaouche K. , Ahmad F. , Armstrong J.M. , Piketty C.
Published: March 2021

Background

Nemolizumab is a humanized anti‐IL‐31 receptor blocker in phase 3 for atopic dermatitis (AD).

Objective

Analyse onset of action of nemolizumab 30 mg and compare efficacy and safety vs placebo (SC q4wk plus loading dose) in moderate‐to‐severe AD.

Methods

Post hoc analysis of patients with Eczema Area and Severity Index (EASI) scores ≥ 16 from a phase 2b trial of moderate‐to‐severe AD. Endpoints were change in EASI score at week 16, peak pruritus numeric rating scale (PP‐NRS), Investigator’s Global Assessment (IGA), changes in sleep and responders with ≥ 4‐point improvement on PP‐NRS.

Results

There was a significantly greater itch relief apparent by Day 2 (−22.8% vs –12.3% PP‐NRS; P = 0.005) which continued to improve through week 16 (−68.5% vs −30.9% PP‐NRS; P < 0.001). At week 16, PP‐NRS ≥ 4‐point response of itch was observed in 68.0% nemolizumab vs 15.9% placebo patients (P ≤ 0.001). There was also a rapid improvement of sleep disturbance with nemolizumab 30 mg, with a significant separation from placebo by Day 3 (−26.6% vs –9.0%; P < 0.001) which further improved till week 16 (−76.0% vs −36.5%; P < 0.001). Also for the EASI score a separation between groups in favour of nemolizumab was observed by week 1 (P ≤ 0.001), which increased through week 16 (−68.6% vs. −42.6%; P = 0.002). Finally, the degree of response was greater in nemolizumab‐treated patients; clinically relevant reductions of 75% EASI were observed in 50.0% of nemolizumab patients versus 15.9% of placebo patients, while 90% reductions were reported for 36.0% and 6.8% of patients, respectively (P < 0.001 for both). IGA success (score of 0/1) was 32.0% for nemolizumab vs 6.8% for placebo (P = 0.002).

Nemolizumab was safe and well‐tolerated in this population; nasopharyngitis and upper respiratory tract infection were the most common adverse events.

Conclusions

Nemolizumab resulted in very rapid, sustained improvements of inflammation, pruritus and sleep in patients with EASI ≥ 16 at baseline.
Connecting Provider to home: A home‐based social intervention program for older adults
Authors: Moreno Gerardo , Mangione Carol M. , Tseng Chi‐Hong , Weir Melanie , Loza Rosaneli , Desai Lisa , Grotts Jonathan , Gelb Eve
Published: March 2021

Objective

Patients with multiple medical conditions and complex social issues are at risk for high utilization and poor outcomes. The Connecting Provider to Home program deployed teams of a social worker and a community health worker (CHW) to support patients with social issues and access to primary care. Our objectives were to examine the impact of the program on utilization and satisfaction with care among older adults with complex social and medical issues.

Design

Retrospective quasi‐experimental observational study with matched comparator group.

Setting

Community‐based program in Southern California.

Participants

Four hundred twenty community dwelling adults.

Intervention

Community‐based healthcare program delivered by a social worker and CHW team for older adults with complex medical and social needs.

Measurements

Acute hospitalization and emergency department (ED) visits in the 12 months preceding and following enrollment in the pilot program. A “difference‐in‐difference” analysis using a matched comparator group was conducted. Comparator group data of patients receiving usual care were obtained. Surveys were conducted to assess patient satisfaction and experiences with the program.

Results

The mean age of patients was 74 years, and the program demonstrated statistically significant reductions in acute hospitalizations and ED use compared with 700 comparator patients. Pre/post‐acute hospitalizations and ED visits were reduced in the intervention group. The average per patient per year reduction in acute hospitalizations was −0.66, whereas the average per patient reduction in ED use was −0.57. Patients enrolled in the program reported high levels of satisfaction and rated the program favorably.

Conclusions

A care model with a social worker and CHW can be linked to primary care to address patient social needs and potentially reduce utilization of healthcare services and enhance patient experiences with care.
Root developmental responses to phosphorus nutrition
Authors: Liu Dong
Published: March 2021

Phosphorus is an essential macronutrient for plant growth and development. Root system architecture (RSA) affects a plant's ability to obtain phosphate, the major form of phosphorus that plants uptake. In this review, I first consider the relationship between RSA and plant phosphorus‐acquisition efficiency, describe how external phosphorus conditions both induce and impose changes in the RSA of major crops and of the model plant Arabidopsis, and discuss whether shoot phosphorus status affects RSA and whether there is a universal root developmental response across all plant species. I then summarize the current understanding of the molecular mechanisms governing root developmental responses to phosphorus deficiency. I also explore the possible reasons for the inconsistent results reported by different research groups and comment on the relevance of some studies performed under laboratory conditions to what occurs in natural environments.
SIZ1 negatively regulates aluminum resistance by mediating the STOP1–ALMT1 pathway in Arabidopsis
Authors: Xu Jiameng , Zhu Jiayong , Liu Jiajia , Wang Junxia , Ding Zhaojun , Tian Huiyu
Published: March 2021

Sensitive to proton rhizotoxicity 1 (STOP1) functions as a crucial regulator of root growth during aluminum (Al) stress. However, how this transcription factor is regulated by Al stress to affect downstream genes expression is not well understood. To explore the underlying mechanisms of the function and regulation of STOP1, we employed a yeast two hybrid screen to identify STOP1‐interacting proteins. The SUMO E3 ligase SIZ1, was found to interact with STOP1 and mainly facilitate its SUMO modification at K40 and K212 residues. Simultaneous introduction of K40R and K212R substitutions in STOP1 enhances its transactivation activity to upregulate the expression of aluminum‐activated malate transporter 1 (ALMT1) via increasing the association with mediator 16 (MED16) transcriptional co‐activator. Loss of function of SIZ1 causes highly increased expression of ALMT1, thus enhancing Al‐induced malate exudation and Al tolerance. Also, we found that the protein level of SIZ1 is reduced in response to Al stress. Genetic evidence demonstrates that STOP1/ALMT1 is epistatic to SIZ1 in regulating root growth response to Al stress. This study suggests a mechanism about how the SIZ1–STOP1–ALMT1 signaling module is involved in root growth response to Al stress.
Quality of Life in patients with nonalcoholic fatty liver disease: Structure and related factors focusing on illness uncertainty
Authors: Ozawa Naoki , Sato Kazuki , Sugimura Ayumi , Maki Shigeyoshi , Tanaka Taku , Yamamoto Kenta , Ito Takanori , Ishizu Yoji , Kuzuya Teiji , Honda Takashi , Ishigami Masatoshi , Fujishiro Mitsuhiro , Ishikawa Tetsuya , Ando Shoko
Published: March 2021

Aim

Patients with nonalcoholic fatty liver disease (NAFLD) have a low quality of life (QOL) and illness uncertainty. This study examined the structure of QOL and associated factors, including illness uncertainty, among individuals with NAFLD.

Methods

A cross‐sectional survey was conducted using a self‐administered questionnaire for outpatients with NAFLD. QOL was measured using the Short Form‐8. Dietary habits, physical activity level, illness uncertainty, health locus of control, and knowledge of NAFLD were assessed. Path analysis was used to study the associated factors of QOL and their structure, including uncertainty of disease.

Results

Path analysis of 168 NAFLD patients indicated that a high Physical Component Summary score on the Short Form‐8—representing physical QOL—was predicted by a body mass index <25 kg/m2 and high educational level. A high Mental Component Summary score—representing mental QOL—was predicted by being male, good dietary habits, low illness uncertainty, and presence of consultants. The model showed satisfactory goodness‐of‐fit without being rejected by the chi‐square test (goodness‐of‐fit index = .947, adjusted goodness‐of‐fit index = .917, comparative fit index = .967, root mean square error of approximation = 0.023).

Conclusions

Nurses need to work closely with NAFLD patients as consultants, providing adequate information about the causes, treatments, and dietary habits, and focusing on the individual's perception of health. This could reduce illness uncertainty and contribute to the improvement of QOL.
Protective effects of berberine in a rat model of polycystic ovary syndrome mediated via the PI3K/AKT pathway
Authors: Yu Jia , Ding Caifei , Hua Zhoujia , Jiang Xuejuan , Wang Chenye
Published: March 2021

Background

Ber, a Chinese herbal monomer has been reported to exhibit an array of pharmacological activities related to the lowering of blood glucose and the treatment of polycystic ovarian syndrome (PCOS). In the present study, we aimed to elucidate the effect of berberine (Ber) on a rat model of PCOS mediated via the PI3K/AKT signaling pathway.

Methods

A PCOS animal model was induced with the administration of letrozole, and animals were then randomized into untreated or Ber and metformin hydrochloride treated groups. After administration, fasting blood glucose, HOMA‐IR, fasting insulin (FINS) values, and the serum hormone levels were measured in PCOS rats. The ovarian tissues were stained with hematoxylin and eosin and terminal deoxynucleotidyl transferase‐mediated dUTP‐biotin nick end labeling (TUNEL) for pathological and apoptosis examination. Moreover, the effect of Ber on the proliferation and apoptosis of granulosa cells was detected by CCK‐8 assays and flow cytometry. The influence of Ber on granulosa cells was confirmed by blockade of the PI3K/AKT pathway. In addition, the modulatory effect of the blockade of the PI3K/AKT pathway on the expression of related proteins was demonstrated via western blotting.

Results

We found that Ber was able to restore the serum hormone levels and improve IR in a PCOS rat model. The morphological lesions and apoptosis of the ovary were also restored by the Ber treatment. Blockade of the PI3K/AKT pathway attenuated the influences of Ber on the proliferation and apoptosis of granulosa cells.

Conclusion

The beneficial effects of Ber on PCOS included alterations of the serum hormone levels, recovery of morphological lesions in the ovary, improvement of insulin resistance, and cell viability and inhibition of apoptosis, which were all mediated through the PI3K/AKT pathway.
Metabolomics of gingival crevicular fluid to identify biomarkers for periodontitis: A systematic review with meta‐analysis
Authors: Baima Giacomo , Corana Matteo , Iaderosa Giovanni , Romano Federica , Citterio Filippo , Meoni Gaia , Tenori Leonardo , Aimetti Mario
Published: March 2021

The present systematic review aimed to examine periodontitis‐specific biomarkers in the gingival crevicular fluid (GCF) that could have a diagnostic relevance, and to provide a qualitative assessment of the current literature. Metabolites are reliable indicators of pathophysiological statuses, and their quantification in the GCF can provide an outlook of the changes associated with periodontitis and have diagnostic value. Relevant studies identified from PubMed, Embase, Cochrane Library, and Scopus databases were examined to answer the following PECO question: “In systemically healthy individuals, can concentration of specific metabolites in the GCF be used to discriminate subjects with healthy periodontium (H) or gingivitis from patients with periodontitis (P) and which is the diagnostic accuracy?” Quality of included studies was rated using a modified version of the QUADOMICS tool. Meta‐analysis was conducted whenever possible. After the screening of 1,554 titles, 15 studies were selected, with sample size ranging from 30 to 93 subjects. Eleven studies performed targeted metabolomics analysis and provided data for 10 metabolites. Among the most consistent markers, malondialdehyde levels were found higher in the P group compared with H group (SMD = 2.86; 95% CI: 1.64, 4.08). Also, a significant increase of 8‐hydroxy‐deoxyguanosine, 4‐hydroxynonenal, and neopterin was detected in periodontally diseased sites, while glutathione showed an inverse trend. When considering data from untargeted metabolomic analysis in four studies, more than 40 metabolites were found significantly discriminant, mainly related to amino acids and lipids degradation pathways. Notably, only one study reported measures of diagnostic accuracy. Several metabolites were differentially expressed in GCF of subjects across different periodontal conditions, having a major potential for investigating periodontal pathophysiology and for site‐specific diagnosis. Oxidative stress‐related molecules, such as malondialdehyde and 8‐hydroxy‐deoxyguanosine, were the most consistently associated to periodontitis (PROSPERO CRD42020188482).
Through the 21st century looking glass: Liberalism, democracy, and populism in a pre‐Yugoslav Serbia
Authors: Guzina Dejan
Published: March 2021

An often underrated but significant debate among Serbian intellectuals is how best to interpret Serbia's political development from the late nineteenth to the early twentieth centuries. Conventional, mainstream understanding is that this period culminated in the golden era of Serbian democracy that lasted from 1903 to 1914. I identify this approach as a liberal‐national interpretation of this period. On their part, Serbian critical historians envision this period in terms of failed modernisation that led to the development of Serbian populism and ethnic nationalism. Even though these depictions involve opposing historical framings of Serbia's past, they both reproduce an ideological picture of the Serbian past rooted within a binary civic/ethnic nationalism framework that constrains analyses of this period to either a modernising civic era or a period that fostered the foundations for ethnic nationalism. Moreover, I argue that, at the discursive level, the debate is not about the past at all. It is primarily about interpreting the contemporary Serbian political system, the role Serbian intellectuals play in it, and whether successful democratisation in a Serbian society could be organised on the principles of further expansion, centralisation, and national homogenisation.
3D morphometric quantification of maxillae and defects for patients with unilateral cleft palate via deep learning‐based CBCT image auto‐segmentation
Authors: Wang Xiaoyu , Pastewait Matthew , Wu Tai‐Hsien , Lian Chunfeng , Tejera Beatriz , Lee Yan‐Ting , Lin Feng‐Chang , Wang Li , Shen Dinggang , Li Song , Ko Ching‐Chang
Published: March 2021

Objective

This study aimed to quantify the 3D asymmetry of the maxilla in patients with unilateral cleft lip and palate (UCP) and investigate the defect factors responsible for the variability of the maxilla on the cleft side using a deep‐learning‐based CBCT image segmentation protocol.

Setting and sample population

Cone beam computed tomography (CBCT) images of 60 patients with UCP were acquired. The samples in this study consisted of 39 males and 21 females, with a mean age of 11.52 years (SD = 3.27 years; range of 8‐18 years).

Materials and methods

The deep‐learning‐based protocol was used to segment the maxilla and defect initially, followed by manual refinement. Paired t‐tests were performed to characterize the maxillary asymmetry. A multiple linear regression was carried out to investigate the relationship between the defect parameters and those of the cleft side of the maxilla.

Results

The cleft side of the maxilla demonstrated a significant decrease in maxillary volume and length as well as alveolar length, anterior width, posterior width, anterior height and posterior height. A significant increase in maxillary anterior width was demonstrated on the cleft side of the maxilla. There was a close relationship between the defect parameters and those of the cleft side of the maxilla.

Conclusions

Based on the 3D volumetric segmentations, significant hypoplasia of the maxilla on the cleft side existed in the pyriform aperture and alveolar crest area near the defect. The defect structures appeared to contribute to the variability of the maxilla on the cleft side.
Comparison of Ultrasound‐Guided Type‐II Pectoral Nerve Block and Rhomboid Intercostal Block for Pain Management Following Breast Cancer Surgery: A Randomized, Controlled Trial
Authors: Ciftci Bahadir , Ekinci Mursel , Basim Pelin , Celik Erkan Cem , Tukac Ismail Cem , Zenciroglu Mahmut , Atalay Yunus Oktay
Published: March 2021

Purpose

Although breast‐conserving surgery‐axillary dissection (BCS‐AD) is a minimally invasive surgery, patients may suffer from moderate‐to‐severe pain. Several regional techniques can be used for pain control. The type II pectoral nerve block (PECS II) and the rhomboid intercostal block (RIB) are interfascial plane blocks that have been reported to provide effective analgesia after breast surgery. This study aims to compare the analgesic efficacy of the PECS II block and the RIB after breast surgery.

Patients and Methods

Ninety female patients aged 18 to 65 years with American Society of Anesthesiologists (ASA) classes I and II physical status who underwent unilateral BCS‐AD surgery were included. Patients were divided into three groups (n = 30 in each): the PECS II group, the RIB group, or the control group. PECS II block and RIB were performed with 30 mL 0.25% bupivacaine. Ibuprofen 400 mg IV 3 × 1 was given in the postoperative period. A patient control analgesia device included a dose of 10 µg/mL fentanyl, which was prepared and connected to the patients.

Results

There were no statistical differences between groups in terms of demographical data. Postoperative fentanyl consumption was significantly lower in the PECS II and RIB groups than the control group. The need for rescue analgesia use was significantly higher in the control group than the other groups. At all times, visual analog scale scores were significantly lower in the PECS II and RIB groups than the control group.

Conclusions

The PECS II block and the RIB provide similar effective analgesia after BCS‐AD.
Combination of Pain Location and Pain Duration is Associated with Central Sensitization‐Related Symptoms in Patients with Musculoskeletal Disorders: A Cross‐Sectional Study
Authors: Tanaka Katsuyoshi , Nishigami Tomohiko , Mibu Akira , Imai Ryota , Manfuku Masahiro , Tanabe Akihito
Published: March 2021

Objectives

Increased evidence indicates that pain location affects central sensitization (CS)‐related symptoms. In addition, pain location and pain duration may be intricately related to CS‐related symptoms. However, these factors have been investigated separately. This study aimed to investigate the association between CS‐related symptoms and pain location and/or pain duration in patients with musculoskeletal disorders.

Methods

Six hundred thirty‐five participants with musculoskeletal disorders were included in this cross‐sectional study. All participants were assessed for pain location, pain duration, central sensitization inventory (CSI), EuroQol‐5 dimension, and brief pain inventory. The participants were categorized into 3 groups based on pain location (spinal, limb, and both spinal and limb pain) and into 2 groups based on pain duration (acute and chronic pain).

Results

The interaction between pain location and pain duration were not significant on CSI score (P > 0.05). The odds ratio for higher CSI score (≥ 40) in patients with both spinal and limb pain vs. those with spinal or limb pain was 2.64 (P < 0.01) and that in patients with chronic pain vs. those with acute pain was 1.31 (P = 0.52). In addition, the prevalence of higher CSI scores in the combination of chronic and “both spinal and limb” pain was high (23.1%, adjusted residual = 4.48).

Conclusions

Pain location independently influenced CSI scores, and the combination of both spinal and limb pain and chronic pain indicated high CSI scores. The combination of pain location and pain duration is an important clue that points to CS‐related symptoms.