bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing equivalence of two doses of intravenous iron to treat iron deficiency in pregnancy: A randomised controlled trial
Authors: Froessler Bernd , Schubert Klaus Oliver , Palm Peter , Church Richard , Aboustate Natalie , Kelly Thu‐Lan , Dekker Gus A. , Hodyl Nicolette A.
Published: September 2022

Objective

To test the equivalence of two doses of intravenous iron (ferric carboxymaltose) in pregnancy.

Design

Parallel, two‐arm equivalence randomised controlled trial with an equivalence margin of 5%.

Setting

Single centre in Australia.

Population

278 pregnant women with iron deficiency.

Methods

Participants received either 500 mg (n = 152) or 1000 mg (n = 126) of intravenous ferric carboxymaltose in the second or third trimester.

Main outcome measures

The proportion of participants requiring additional intravenous iron (500 mg) to achieve and maintain ferritin >30 microg/L (diagnostic threshold for iron deficiency) at 4 weeks post‐infusion, and at 6 weeks, and 3‐, 6‐ and 12‐months postpartum. Secondary endpoints included repeat infusion rate, iron status, birth and safety outcomes.

Results

The two doses were not equivalent within a 5% margin at any time point. At 4 weeks post infusion, 26/73 (36%) participants required a repeat infusion in the 500‐mg group compared with 5/67 (8%) in the 1000‐mg group: difference in proportions, 0.283 (95% confidence interval [CI] 0.177–0.389). Overall, participants in the 500‐mg arm received twice the repeat infusion rate (0.81 [SD = 0.824] versus 0.40 [SD = 0.69], rate ratio 2.05, 95% CI 1.45–2.91).

Conclusions

Administration of 1000 mg ferric carboxymaltose in pregnancy maintains iron stores and reduces the need for repeat infusions. A 500‐ mg dose requires ongoing monitoring to ensure adequate iron stores are reached and sustained.
Spatial density estimate of the snow leopard,Panthera uncia, in the Central Tibetan Plateau, China
Authors: BIAN Xiaoxing , LIANG Xuchang , WECKWORTH Byron , JYAL Dorje , HULL Vanessa , YANG Le
Published: September 2022

Knowledge of large carnivore population abundance is essential for wildlife management and conservation, but these data are often difficult to obtain in inherently low‐density species. In particular, the snow leopard,Panthera uncia, an enigmatic cat occupying remote mountains in Central Asia, has received insufficient assessments of its population abundance because of logistical and methodological challenges. Here, we aimed to develop a robust density estimation of snow leopards based on 81 days of camera trapping within a contiguous and previously unsurveyed 1950 km2area of habitat on the Tibetan Plateau (Mayue Township, Shenzha County, Tibet Autonomous Region, China). By applying spatially explicit capture–recapture models, we produced an estimate of 1.40 (95%CI: 1.06–1.84) individuals per 100 km2. Results also suggested sex‐specific variation in the range of movement around activity centers, with male (N= 10, σ = 4.02) movement considerably greater than female (N= 8, σ = 1.84) movement. The findings can serve as a reliable baseline reference for assessing the population trends of this endangered felid species with future estimates. This study will provide context to contribute toward a better understanding of ecological factors shaping the distribution and abundance of snow leopards and the related conservation measures needed to sustain their long‐term survival on the Tibetan Plateau.
trans‐Cinnamaldehyde‐encapsulated zeolitic imidazolate framework‐8 nanoparticle complex solutions to inactivate Escherichia coli O157:H7 on fresh spinach leaves
Authors: Yang Xiaoying , Castell‐Perez Maria Elena , Moreira Rosana G. , Sevimli‐Yurttas Zeynep
Published: September 2022

This study synthesized and characterized ZIF‐8 nanoparticles encapsulated with trans‐cinnamaldehyde oil (TC) and evaluated their antimicrobial effectiveness against Escherichia coli O157:H7 on fresh spinach leaves. The antimicrobial activity of different mass ratios of TC‐encapsulated ZIF‐8 against E. coli O157:H7 (ATCC 43895) strain was assessed and the best mass ratio of 1:2 TC to ZIF‐8 identified. Spinach leaves were treated with (1) 0.5TC@ZIF‐8_PL nanoparticle complexes solution, (2) 200 ppm chlorine, (3) free TC, and (4) sterilized distilled water (control). All sample groups were rinsed for 1 min, dried in a biosafety cabinet, weighted, and packed in sterilized Whirl‐pkTM Stand‐Up sampling bags, and stored at 4°C for 15 days for shelf life studies. Samples were dipped into a solution of nanoparticles and another group was sprayed. The quality of spinach samples was assessed by monitoring changes in moisture content (MC), water activity (Aw), color, pH, texture (firmness and work), vitamin C content, total carotenoid, and chlorophyll content. Spinach leaves treated with 0.5TC@ZIF‐8_PL had less (p < 0.05) water, total chlorophyll, and total carotenoid losses, with minimal changes in pH. However, treatment did not prevent the color degradation (p > 0.05) and adversely affected spinach firmness. The spinach samples treated with 200 ppm chlorine and free TC had higher (p < 0.05) total chlorophyll degradation than the samples treated with the nanoparticles. The mass ratio of TC‐encapsulated ZIF‐8 must be readjusted to reduce potential toxicity issues while maintaining the antimicrobial properties.

Practical Application

Zeolitic imidazolate framework‐8 (ZIF‐8) nanoparticle complex can be used to encapsulate natural antimicrobials to inhibit growth of pathogens on fresh produce. A 2‐log reduction in populations of Escherichia coli O157:H7 on fresh spinach leaves was achieved using trans‐cinnamaldehyde at low concentrations. The results can be used to embed the compounds into polymeric films for antimicrobial packaging applications.
Classic psychedelics and alcohol use disorders: A systematic review of human and animal studies
Authors: Calleja‐Conde Javier , Morales‐García Jose Angel , Echeverry‐Alzate Víctor , Bühler Kora Mareen , Giné Elena , López‐Moreno Jose Antonio
Published: September 2022

Classic psychedelics refer to substances such as lysergic acid diethylamide (LSD), psilocybin, ayahuasca, and mescaline, which induce altered states of consciousness by acting mainly on 5‐HT2A receptors. Recently, the interest of psychedelics as pharmacological treatment for psychiatric disorders has increased significantly, including their use on problematic use of alcohol. This systematic review is aimed to analyse the last two decades of studies examining the relationship between classic psychedelics and alcohol consumption. We searched PubMed and PsycInfo for human and preclinical studies published between January 2000 to December 2021. The search identified 639 publications. After selection, 27 studies were included. Human studies (n = 20) generally show promising data and seem to indicate that classic psychedelics could help reduce alcohol consumption. Nevertheless, some of these studies present methodological concerns such as low number of participants, lack of control group or difficulty in determining the effect of classic psychedelics in isolation. On the other hand, preclinical studies (n = 7) investigating the effect of these compounds on voluntary alcohol consumption are scarce and show some conflicting data. Among these compounds, psilocybin seems to show the most consistent data indicating that this compound could be a potential candidate to treat alcohol use disorders. In the absence of understanding the biological and/or psychological mechanisms, more studies including methodological quality parameters are needed to finally determine the effects of classic psychedelics on alcohol consumption.
Measuring aerosols in the operating theatre and beyond using a real‐time sensor network
Authors: Hecker J. G. , He J. , Rochlin R. , Brannen C. , Teng S. , Glenn K. , Novosselov I.
Published: September 2022

The ability to measure and track aerosols in the vicinity of patients with suspected or confirmed COVID‐19 is highly desirable. At present, there is no way to measure and track, in real time, the sizes, dispersion and dilution/disappearance of aerosols that are generated by airway manipulations such as mask ventilation; tracheal intubation; bronchoscopy; dental and gastro‐intestinal endoscopy procedures; or by vigorous breathing, coughing or exercise. We deployed low‐cost photoelectric sensors in five operating theatres between surgical cases. We measured and analysed dilution and exfiltration of aerosols we generated to evaluate air handling and dispersion under real‐world conditions. These data were used to develop a model of aerosol persistence. We found significant variation between different operating theatres. Equipment placement near air vents affects air flows, impacting aerosol movement and elimination patterns. Despite these impediments, air exchange in operating theatres is robust and prolonged fallow time before theatre turnover may not be necessary. Significant concentrations of aerosols are not seen in adjoining areas outside of the operating theatre. These models and dispersion rates can predict aerosol persistence in operating theatres and other clinical areas and potentially facilitate quantification of risk, with obvious and far‐reaching implications for designing, evaluating and confirming air handling in non‐medical environments.
An algorithm for the management of traumatic abdominal wall hernia based on a 9‐year review
Authors: Wong Jessica , Peng Calvin , Shakerian Rose , Knowles Brett , Thomson Ben , Read David J.
Published: September 2022

Background

Traumatic abdominal wall hernia (TAWH) is a rare consequence of blunt abdominal trauma, usually in the setting of multitrauma, with little consensus or guidelines for management. We present a case series of patients with traumatic herniae over a 9‐year period and a suggested management algorithm.

Method

Retrospective review of all patients with TAWH from 1st January 2011 to 31st December 2019 at a Level 1 adult Major Trauma Centre. Clinical presentation, surgical intervention and complications and recurrence were analysed.

Results

Forty‐seven patients were found to have TAWH, 0.5% of all major trauma admissions. Thirty (63.8%) were repaired, 12 acutely, 11 semi‐acute and 7 delayed. All but 1 (fall>3 m) were transport associated, with a median Injury Severity Score (ISS) of 29. Follow‐up data for operative cases were available for all but one (97%). Seven (23.3%) cases had a recurrence, more common in the acute repair group (33.3%) compared to semi‐acute (18.2%), and elective group (14.3%).

Conclusion

TAWH is a rare but potentially serious consequence of blunt abdominal trauma. This series has favoured earlier repair for anterior TAWH, or all those undergoing a laparotomy for other reasons, and elective repair for lumbar or lateral TAWH that do not require a laparotomy for other conditions. We present our preferred algorithm for management, accepting that there are many available strategies in this heterogeneous group of injuries. Loss of follow up and recurrence are a concern, and clinicians are encouraged to develop processes to ensure that TAWH are not a ‘forgotten hernia’.
Paving the road to make chimeric antigen receptor‐T‐cell therapy effective against solid tumors
Authors: Adachi Keishi , Tamada Koji
Published: September 2022

The three major standard therapies, that is, surgery, chemotherapy, and radiation therapy have conventionally been applied to the treatments for cancers and have saved many patients. In addition, for intractable, refractory, or advanced malignancies that cannot be cured by the three standard therapies, immunotherapy is an important subject of basic and clinical researches. Immune checkpoint inhibitor therapy (ICI) has shown significant therapeutic efficacies on some types of tumors in large‐scale randomized clinical trials, making a major impact on clinical oncology by scientifically proving and establishing the effectiveness of an immunotherapy. In 2018, ICI was awarded the Nobel Prize in Physiology or Medicine, and immunotherapy is now becoming the “fourth” standard therapy for cancers. Recently, adoptive cell therapies, in which genetically modified T cells with enhanced reactivity against tumors are infused into the patients, have been attracting considerable attention as a hopeful immunotherapy following ICI. Particularly, chimeric antigen receptor (CAR)‐T‐cell therapies demonstrate marked therapeutic efficacies against some hematologic malignancies, and have been approved in many countries. However, current CAR‐T‐cell therapy is considered to be little effective against solid tumors, which is one of the challenging issues to be overcome in CAR‐T‐cell therapy. In this review, we at first introduce CAR and CAR‐T cell, and then focus on the recent progress of CAR‐T‐cell therapy against solid tumors as well as the novel concept on a role of CAR‐T cells, aiming to further understandings of the novel cancer immunotherapies.
Hereditary spastic paraparesis presenting as cerebral palsy due to ADD3 variant with mechanistic insight provided by a Drosophila γ‐adducin model
Authors: Sanchez Marco Silvia Beatriz , Buhl Edgar , Firth Rose , Zhu Bangfu , Gainsborough Mary , Beleza‐Meireles Ana , Moore Sandra , Caswell Richard , Stals Karen , Ellard Sian , Kennedy Cameron , Hodge James J. L. , Majumdar Anirban
Published: September 2022

Cerebral palsy (CP) causes neurological disability in early childhood. Hypoxic‐ischaemic injury plays a major role in its aetiology, nevertheless, genetic and epigenetic factors may contribute to the clinical presentation. Mutations in ADD3 (encoding γ‐adducin) gene have been described in a monogenic form of spastic quadriplegic cerebral palsy (OMIM 601568). We studied a 16‐year‐old male with spastic diplegia. Several investigations including neurometabolic testing, brain and spine magnetic resonance imaging (MRI) and CGH‐Array were normal. Further, clinical genetics assessment and whole exome sequencing (WES) gave the diagnosis. We generated an animal model using Drosophila to study the effects of γ‐adducin loss and gain of function. WES revealed a biallelic variant in the ADD3 gene, NM_016824.5(ADD3): c.1100G > A, p.(Gly367Asp). Mutations in this gene have been described as an ultra‐rare autosomal recessive, which is a known form of inherited cerebral palsy. Molecular modelling suggests that this mutation leads to a loss of structural integrity of γ‐adducin and is therefore expected to result in a decreased level of functional protein. Pan‐neuronal over‐expression or knock‐down of the Drosophila ortholog of ADD3 called hts caused a reduction of life span and impaired locomotion thereby phenocopying aspects of the human disease. Our animal experiments present a starting point to understand the biological processes underpinning the clinical phenotype and pathogenic mechanisms, to gain insights into potential future methods for treating or preventing ADD3 related spastic quadriplegic cerebral palsy.
Efficacy and safety of 3‐n‐butylphthalide for the treatment of cognitive impairment: A systematic review and meta‐analysis
Authors: Zhou Qiulu , Han Chao , Xia Yun , Wan Fang , Yin Sijia , Li Yunna , Kou Liang , Chi Xiaosa , Hu Junjie , Sun Yadi , Wu Jiawei , Zou Wenkai , Huang Jinsha , Wang Tao
Published: September 2022

Background

Current evidence for the efficacy of pharmacological treatment in improving cognitive function is absent. Recent studies have reported that 3‐n‐butylphthalide (NBP) has a positive effect on improving cognitive impairment; however, its clinical efficacy and safety is unclear. Therefore, we conducted a meta‐analysis to assess its efficacy and safety for cognitive impairment.

Methods

We systematically searched the PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus databases, and two reviewers independently screened and extracted the data from included studies. We synthesized the data using the Review Manager Software version 5.3.

Results

We included six randomized clinical trials (RCTs), encompassing 851 patients with cognitive impairment. The results showed that NBP improved cognitive impairment. Specifically, the clinical efficacy was better than that in the control group, with better performance in improving the Mini‐Mental State Examination and the Montreal Cognitive Assessment scores, while decreasing the Alzheimer's Disease Assessment Scale‐Cognitive subscale and the Clinician's Interview‐Based Impression of Change plus caregiver input scores. There was no significant difference in the incidence of adverse events between both groups.

Conclusion

The NBP is effective and safe in improving cognitive impairment; however, more high‐quality RCTs are needed to confirm these findings.
Exploring metapopulation‐scale suppression alternatives for a global invader in a river network experiencing climate change
Authors: Healy Brian D. , Budy Phaedra , Yackulic Charles. B. , Murphy Brendan P. , Schelly Robert C. , McKinstry Mark C.
Published: September 2022

Invasive species can dramatically alter ecosystems, but eradication is difficult, and suppression is expensive once they are established. Uncertainties in the potential for expansion and impacts by an invader can lead to delayed and inadequate suppression, allowing for establishment. Metapopulation viability models can aid in planning strategies to improve responses to invaders and lessen invasive species’ impacts, which may be particularly important under climate change. We used a spatially explicit metapopulation viability model to explore suppression strategies for ecologically damaging invasive brown trout (Salmo trutta), established in the Colorado River and a tributary in Grand Canyon National Park. Our goals were to estimate the effectiveness of strategies targeting different life stages and subpopulations within a metapopulation; quantify the effectiveness of a rapid response to a new invasion relative to delaying action until establishment; and estimate whether future hydrology and temperature regimes related to climate change and reservoir management affect metapopulation viability and alter the optimal management response. Our models included scenarios targeting different life stages with spatially varying intensities of electrofishing, redd destruction, incentivized angler harvest, piscicides, and a weir. Quasi‐extinction (QE) was obtainable only with metapopulation‐wide suppression targeting multiple life stages. Brown trout population growth rates were most sensitive to changes in age 0 and large adult mortality. The duration of suppression needed to reach QE for a large established subpopulation was 12 years compared with 4 with a rapid response to a new invasion. Isolated subpopulations were vulnerable to suppression; however, connected tributary subpopulations enhanced metapopulation persistence by serving as climate refuges. Water shortages driving changes in reservoir storage and subsequent warming would cause brown trout declines, but metapopulation QE was achieved only through refocusing and increasing suppression. Our modeling approach improves understanding of invasive brown trout metapopulation dynamics, which could lead to more focused and effective invasive species suppression strategies and, ultimately, maintenance of populations of endemic fishes.
Effects of interactions between anthropogenic stressors and recurring perturbations on ecosystem resilience and collapse
Authors: Keith David A. , Benson Doug H. , Baird Ian R. C. , Watts Laura , Simpson Christopher C. , Krogh Martin , Gorissen Sarsha , Ferrer‐Paris Jose R. , Mason Tanya J.
Published: September 2022

Insights into declines in ecosystem resilience and their causes and effects can inform preemptive action to avoid ecosystem collapse and loss of biodiversity, ecosystem services, and human well‐being. Empirical studies of ecosystem collapse are rare and hampered by ecosystem complexity, nonlinear and lagged responses, and interactions across scales. We investigated how an anthropogenic stressor could diminish ecosystem resilience to a recurring perturbation by altering a critical ecosystem driver. We studied groundwater‐dependent, peat‐accumulating, fire‐prone wetlands known as upland swamps in southeastern Australia. We hypothesized that underground mining (stressor) reduces resilience of these wetlands to landscape fires (perturbation) by diminishing groundwater, a key ecosystem driver. We monitored soil moisture as an indicator of ecosystem resilience during and after underground mining. After landscape fire, we compared responses of multiple state variables representing ecosystem structure, composition, and function in swamps within the mining footprint with unmined reference swamps. Soil moisture declined without recovery in swamps with mine subsidence (i.e., undermined), but was maintained in reference swamps over 8 years (effect size 1.8). Relative to burned reference swamps, burned undermined swamps showed greater loss of peat via substrate combustion; reduced cover, height, and biomass of regenerating vegetation; reduced postfire plant species richness and abundance; altered plant species composition; increased mortality rates of woody plants; reduced postfire seedling recruitment; and extirpation of a hydrophilic animal. Undermined swamps therefore showed strong symptoms of postfire ecosystem collapse, whereas reference swamps regenerated vigorously. We found that an anthropogenic stressor diminished the resilience of an ecosystem to recurring perturbations, predisposing it to collapse. Avoidance of ecosystem collapse hinges on early diagnosis of mechanisms and preventative risk reduction. It may be possible to delay or ameliorate symptoms of collapse or to restore resilience, but the latter appears unlikely in our study system due to fundamental alteration of a critical ecosystem driver.

Efectos de las interacciones entre los estresantes antropogénicos y las perturbaciones recurrentes sobre la resiliencia y el colapso de los ecosistemas
Learning from perpetrator replacement to remove crime opportunities and prevent poaching of the Sundarbans tiger
Authors: Uddin Nasir , Enoch Sam , Harihar Abishek , Pickles Rob S. A. , Ara Tasnim , Hughes Alice C.
Published: September 2022

Illegal wildlife trade (IWT) is one of the leading causes of the decline in high‐value species. Crime‐reduction strategies to counter IWT can have unintended effects, with crime displacement occurring when offenders react to such interventions. Despite the value of understanding how and why displacement occurs for informing conservation strategies, few examples are published. We explored a case of perpetrator replacement following an intervention and drew lessons for conservation strategies for high‐value species. Poaching and subsequent trade threaten the Sundarbans tiger (Panthera tigris). Pirate gangs were the dominant poachers from 1980 to 2017, but following an extensive campaign, the Sundarbans was declared pirate free in 2018. We interviewed 280 individuals, including 100 tiger poachers, from 26 administrative unions bordering the Sundarbans and used interviewee responses to compare the poaching situation during and after the pirate era. We analyzed the spatial distribution of tiger poachers among the unions and used crime script analysis of the dominant poacher type to identify intervention. Because pirates opportunistically poached tigers, the government's successful counter‐pirate campaign inadvertently removed the dominant tiger poaching type. However, a temporary reduction in poaching was rapidly cancelled out by the emergence of at least 32 specialist tiger‐poaching teams. With the risk of extortion and robbery from pirates gone, other groups increased the frequency of opportunistic and targeted tiger poaching. Based on expert interviews, we estimated that 341 tiger poachers of all types are active throughout the unions, with 79% of specialists concentrated in 27% of unions. The highly focused counter‐pirate campaign reduced motivations and opportunities for piracy but left intact the opportunity structure and trade connections for tiger poaching, and with insufficient enforcement officers trading has flourished. Interventions targeting opportunities for poaching by specialist tiger poachers include heightened surveillance and reporting mechanisms and alternative livelihood provision to disincentivize poaching.
A phase I, randomized, placebo‐controlled study of molnupiravir in healthy Japanese to support special approval in Japan to treat COVID‐19
Authors: Nakamura Keisuke , Fujimoto Katsukuni , Hasegawa Chihiro , Aoki Ikuo , Yoshitsugu Hiroyuki , Ugai Hiroyuki , Yatsuzuka Naoyoshi , Tanaka Yoshiyuki , Furihata Kenichi , Maas Brian M. , Wickremasingha Prachi K. , Duncan Kelly E. , Iwamoto Marian , Stoch Selwyn A. , Uemura Naoto
Published: September 2022

Molnupiravir (MK‐4482) is an oral prodrug of the antiviral ribonucleoside analog, N‐hydroxycytidine (NHC), which has activity against RNA viruses, including severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). We conducted a phase I safety and pharmacokinetic study of molnupiravir in healthy Japanese adult participants. A sample size larger than typically used in pharmacokinetic studies was implemented to collect additional safety data in the Japanese population to support special approval for emergency use in Japan. Single doses of molnupiravir up to 1600 mg and multiple doses of 400 and 800 mg administered every 12 h (q12h) for 5.5 days were generally well‐tolerated. NHC appeared rapidly in plasma and reached maximum concentration (Cmax), with a median time to Cmax (Tmax) between 1.00 and 2.00 h. Area under the concentration versus time curve from zero to infinity (AUC0–inf), area under the concentration versus time curve from zero to 12 h (AUC0–12), and Cmax of plasma NHC increased approximately dose proportionally. With q12h dosing, the geometric mean (GM) accumulation ratios for NHC AUC0–12 and Cmax were ~1 for 400 and 800 mg. Pharmacokinetics of NHC triphosphate (NHC‐TP), the active metabolite of NHC was assessed in peripheral blood mononuclear cells and also demonstrated roughly dose proportional pharmacokinetics. The GM accumulation ratios for NHC‐TP AUC0–12 and Cmax were ~2.5 for 400 and 800 mg. Following administration with food, only a modest reduction (24%) in plasma NHC Cmax with comparable AUC0–inf was seen, supporting administration without regard to food.
Interleukin‐1α and tumor necrosis factor α as an inducer for reactive‐oxygen‐species‐mediated NOD‐like receptor protein 1/NOD‐like receptor protein 3 inflammasome activation in mononuclear blood cells from individuals with chronic insomnia disorder
Authors: Aghelan Zahra , Karima Saeed , Khazaie Habibolah , Abtahi Seyed Hosein , Farokhi Ali Reza , Rostampour Masoumeh , Bahrehmand Fariborz , Khodarahmi Reza
Published: September 2022

Background and purpose

There is some evidence that cytokines may play an important role in sleep deprivation; however, the underlying mechanisms are still unknown. So, the present study aimed to evaluate the relationship between NOD‐like receptor protein 1 (NLRP1) and NOD‐like receptor protein 3 (NLRP3) inflammasome activation of blood cells and serum levels of cytokines in individuals with chronic insomnia disorder (CID).

Methods

Blood samples were collected from 24 individuals with CID and 24 healthy volunteers. The inflammasome activation was evaluated using real‐time polymerase chain reaction of NLRP1, NLRP3, apoptosis‐associated speck‐like protein containing a caspase‐recruitment domain (ASC) and caspase‐1; western blot of NLRP1 and NLRP3; caspase‐1 activity assay; and serum levels of interleukin‐1β (IL‐1β), IL‐18 and other cytokines using enzyme‐linked immunosorbent assay. Reactive oxygen species generation in blood cells were detected by flow cytometry assay. Also, magnetic resonance imaging scans were obtained on a Siemens Magnetom Avanto 1.5 T MRI whole‐body scanner using an eight‐channel head coil.

Results

Increased activity of NLRP1 and NLRP3 inflammasomes in blood cells, increased serum levels of pro‐inflammatory cytokines and decreased serum levels of IL‐10 and transforming growth factor β in individuals with CID were found. Significant correlation was observed between increased serum concentration of IL‐1β and the severity of insomnia in individuals with CID. The levels of reactive oxygen species in blood cells were found to be correlated with IL‐1α and tumor necrosis factor α concentrations in sera from individuals with CID. Moreover, the individuals with CID demonstrated increased right cerebellum cortex and lateral ventricle mean diffusivity bilaterally compared to controls.

Conclusions

This study provided new insights on the pathogenesis of CID and the effects of cytokines on inflammasome activation.
Validation of motor and functional scales for the evaluation of adult patients with 5q spinal muscular atrophy
Authors: Vázquez‐Costa Juan F. , Povedano Mónica , Nascimiento‐Osorio Andrés E. , Moreno Escribano Antonio , Kapetanovic Garcia Solange , Dominguez Raul , Exposito Jessica M. , González Laura , Marco Carla , Medina Castillo Julita , Muelas Nuria , Natera de Benito Daniel , Ñungo Garzón Nancy Carolina , Pitarch Castellano Inmaculada , Sevilla Teresa , Hervás David
Published: September 2022

Background and purpose

Mos scales currently used to evaluate spinal muscular atrophy (SMA) patients have only been validated in children. The aim of this study was to assess the construct validity and responsiveness of several outcome measures in adult SMA patients.

Methods

Patients older than 15 years and followed up in five referral centres for at least 6 months, between October 2015 and August 2020, with a motor function scale score (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb module [RULM]) were included. Bedside functional scales (Egen Klassification [EK2], Revised Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS‐R]) were also collected when available. Spearman's rho correlations (rs) and Bangdiwala's concordance test (B) were used to evaluate the scales' construct validity. Monthly slopes of change were used to calculate their responsiveness of the scales.

Results

The study included 79 SMA patients, followed up for a mean of 16 months. All scales showed strong correlations with each other (rs > 0.70). A floor effect in motor function scales was found in the weakest patients (HFMSE < 5 and RULM < 10), and a ceiling effect was found in stronger patients (HFMSE > 60 and RULM > 35). The ALSFRS‐R (B = 0.72) showed a strong ability to discriminate between walkers, sitters and non‐sitters, and the HFMSE (B = 0.86) between walkers and sitters. The responsiveness was low overall, although in treated patients a moderate responsiveness was found for the ALSFRS‐R and HFMSE in walkers (0.69 and 0.61, respectively) and for EK2 in sitters (0.65) and non‐sitters (0.60).

Conclusions

This study shows the validity and limitations of the scales most frequently used to assess adult SMA patients. Overall, bedside functional scales showed some advantages over motor scales, although all showed limited responsiveness.
The UV‐induced uptake of melanosome by skin keratinocyte is triggered by α7 nicotinic acetylcholine receptor‐mediated phagocytosis
Authors: Guo Maggie Suisui , Wu Qiyun , Dong Tina Tingxia , Tsim Karl Wah Keung
Published: September 2022

The melanosome is an organelle that produces melanin for skin pigmentation, which is synthesized by epidermal melanocytes, subsequently transported and internalized by epidermal keratinocytes. Exposure to ultraviolet (UV) from sunlight radiation is a major stimulator of melanosome uptake by keratinocytes. Acetylcholine (ACh) is known to be released by keratinocytes under UV exposure, which regulates melanin production in melanocytes by participating in which has been named as ‘skin synapse’. Here, the role of cholinergic molecules, i.e. ACh and α7 nicotinic acetylcholine receptor (nAChR), in regulating melanosome uptake through phagocytosis by keratinocytes was illustrated. In cultured keratinocytes (HaCaT cells), the fluorescent beads at different sizes imitating melanosomes, or melanosomes, were phagocytosed under UV exposure. The UV‐induced phagocytosis in keratinocytes was markedly increased by applied ACh, an acetylcholinesterase (AChE) inhibitor or an α7 nAChR agonist. By contrast, the antagonist of α7 nAChR was able to fully block the UV‐induced phagocytosis, suggesting the role of α7 nAChR in this event. The intracellular Ca++ mobilization was triggered by UV exposure, accounting for the initiation of phagocytosis. The blockage of UV‐mediated Ca++ mobilization, triggered by BAPTA‐AM or α7 nAChR antagonist, resulted in a complete termination of phagocytosis. Besides, the phosphorylation of cofilin, as well as expression and activation of RhoA, accounting for phagocytosis was induced by UV exposure: the phosphorylation was blocked by BAPTA‐AM or α7 nAChR antagonist. The result suggests that the cholinergic system, especially α7 nAChR, is playing a regulatory role in modulating melanosome uptake in keratinocytes being induced by UV exposure.
Targeting glucose‐6‐phosphate dehydrogenase by 6‐AN induces ROS‐mediated autophagic cell death in breast cancer
Authors: Li Yin , Zheng Fangxu , Zhang Yupeng , Lin Zhoujun , Yang Juan , Han Xiao , Feng Ya , Pei Xiaolin , Li Fei , Liu Qiao , Yan Lizhong , Li Tianjiao , Zhang Yifan , Li Ding , Fu Zhenkun , Wang Changjun , Sun Qiang , Li Chenggang
Published: September 2022

Dysregulation of G6PD involved in the pentose phosphate pathway (PPP) is known to promote tumorigenesis. The PPP plays a pivotal role in meeting the anabolic demands of cancer cells. However, the detailed underlying molecular mechanisms of targeting the G6PD‐regulated PPP in breast cancer remain unclear. In this study, we aimed to elucidate the molecular pathways mediating the effects of G6PD on cancer progression. Clinical sample analysis found that the expression of G6PD in breast cancer patients was higher than that in normal controls, and patients with higher G6PD expression had poor survival. Gene knockdown or inhibition of G6PD by 6‐AN in MCF‐7 and MDA‐MB‐231 cells significantly decreased cell viability, migration, and colony formation ability. G6PD enzyme activity was inhibited by 6‐AN treatment, which caused a transient upregulation of ROS. The elevated ROS was independent of cell apoptosis and thus associated with abnormal activated autophagy. Accumulated ROS levels induced autophagic cell death in breast cancer. Inhibition of G6PD suppresses tumour growth in preclinical models of breast cancer. Our results indicate that targeting the G6PD‐regulated PPP could restrain tumours in vitro and in vivo, inhibiting G6PD caused cell death by over‐activating autophagy, therefore leading to inhibited proliferation and tumour formation.
The coordination of green–brown food webs and their disruption by anthropogenic nutrient inputs
Authors: Zelnik Yuval R. , Manzoni Stefano , Bommarco Riccardo
Published: September 2022

Aim

Our goal was to quantify nitrogen flows and stocks in green–brown food webs in different ecosystems, how they differ across ecosystems and how they respond to nutrient enrichment.

Location

Global.

Time period

Contemporary.

Major taxa studied

Plants, phytoplankton, macroalgae, invertebrates, vertebrates and zooplankton.

Methods

Data from >500 studies were combined to estimate nitrogen stocks and fluxes in green–brown food webs in forests, grasslands, brackish environments, seagrass meadows, lakes and oceans. We compared the stocks, fluxes and metabolic rates of different functional groups within each food web. We also used these estimates to build a dynamical model to test the response of the ecosystems to nutrient enrichment.

Results

We found surprising symmetries between the green and brown channels across ecosystems, in their stocks, fluxes and consumption coefficients and mortality rates. We also found that nitrogen enrichment, either organic or inorganic, can disrupt this balance between the green and brown channels.

Main conclusions

Linking green and brown food webs reveals a previously hidden symmetry between herbivory and detritivory, which appears to be a widespread property of natural ecosystems but can be disrupted by anthropogenic nitrogen additions.
Factors associated with patient empowerment in Spanish adults with type 2 diabetes: A cross‐sectional analysis
Authors: Duarte‐Díaz Andrea , González‐Pacheco Himar , Rivero‐Santana Amado , Ramallo‐Fariña Yolanda , Perestelo‐Pérez Lilisbeth , Peñate Wenceslao , Carrion Carme , Serrano‐Aguilar Pedro ,   INDICA Team
Published: September 2022

Objective

The aim of the present study is to identify factors associated with patient empowerment in people living with type 2 diabetes mellitus (T2DM) in the Canary Islands (Spain).

Methods

Secondary cross‐sectional analysis was carried out of data obtained in the INDICA study: A 24‐month cluster randomized‐controlled trial evaluating the effectiveness of educational interventions supported by new technology decision tools for T2DM patients. Sociodemographic variables, clinical data (years since diagnosis, glycated haemoglobin level, creatine, triglycerides, waist hip index, body mass index and number of comorbidities), diabetes knowledge (DIATEK), affective outcomes (Beck Depression Inventory‐II, the State subscale of the State‐Trait Anxiety Inventory and The Diabetes Distress Scale) and diabetes‐related quality of life (The Audit of Diabetes‐Dependent Quality of life) were assessed as potential correlates of patient empowerment, assessed using the Diabetes Empowerment Scale‐Short Form. Multilevel mixed linear regression models on patient empowerment were developed.

Results

The analysis included the baseline data of 2334 patients. Results showed that age (B = −0.14; p < .001), diabetes knowledge (B = 0.61; p < .001) and state‐anxiety (B = −0.09; p < .001) are significantly associated with patient empowerment. Sex, education level, living alone, employment status, country of birth, time since diagnosis, number of comorbidities, glycated haemoglobin level, depression and distress were not independently associated with patient empowerment in the multivariate analyses.

Conclusion

Younger age, lower state‐anxiety and greater diabetes‐specific knowledge are important correlates of patient empowerment. In line with the results of the INDICA study, interventions based on patient‐centred care might be effective in improving patient empowerment in adults with T2DM. Understanding the factors associated with empowerment may help clinicians and policymakers to identify high‐risk groups, prioritize resources and target evidence‐based interventions to better support people with T2DM to be actively involved in their own care.

Patient or Public Contribution

Patients with T2DM were actively involved in the design of the INDICA study. Two patient associations were included as part of the research team and actively participated in designing the interventions and selecting outcome measures.
Survivor‐led guidelines for conducting trauma‐informed psychological therapy assessments: Development and modified Delphi study
Authors: Sweeney Angela , White Sarah , Kelly Katie , Faulkner Alison , Papoulias Stan , Gillard Steve
Published: September 2022

Background

Psychological therapy assessments are a key point at which a person is accepted into a service or referred on. There is evidence of service users experiencing harm, dropping out of services and potentially experiencing poor outcomes because of inadequate assessment practices. Approaches to assessment tend to be developed by individual services, with a lack of research identifying what makes a good assessment.

Methods

This survivor‐led study, based in England, aimed to generate guidelines for conducting trauma‐informed psychological therapy assessments. The study was guided by a Service User Advisory Group and a Clinician Advisory Group. The study was conducted in three key stages: (i) identifying, modelling and drafting guideline content (ii) modified Delphi study and (iii) guideline finalization. Stage 1 was informed by literature reviews, qualitative research, data workshops with Advisory Groups and an expert consultation. Fifty‐nine people with relevant experiences then participated in a single‐stage modified Delphi (Stage 2). The guidelines were finalized through an analysis of Delphi open comments and a final expert consultation (Stage 3).

Results

The guidelines evolved through each stage of the process, and all items were deemed important by >90% of Delphi participants. The final trauma‐informed guidelines contain eight principles, including ‘focus on relationships’, ‘from systems to people’ and ‘healing environments’.

Conclusions

Experiential knowledge was key in generating the guidelines and conceptualizing content, with a consequent focus on areas, such as recognizing power differentials, understanding oppression as trauma and the relational aspects of assessments. Future research should focus on guideline implementation and investigate whether this impacts service user dropout, engagement with therapy, and outcomes.

Patient or Public Contribution

This study is an example of survivor research, with several authors, including the study lead, identifying as survivors. We consider the ways in which our identities as survivor researchers impacted the study findings.
High nest failure but better nestling quality for early breeders in an alpine population of Northern Wheatear (Oenanthe oenanthe)
Authors: Sander Martha Maria , Jähnig Susanne , Lisovski Simeon , Mermillon Camille , Alba Riccardo , Rosselli Domenico , Chamberlain Dan
Published: September 2022

Climate change is leading to the advancement of spring conditions, resulting in an earlier snowmelt and green‐up, with highest rates of change in highly seasonal environments, including alpine habitats. Migratory birds breeding at high elevations need to time their arrival and lay dates accurately with this advancement, but also with the annually variable spring conditions at their breeding sites, to maximize nest survival probabilities and reproductive output. Nest survival probability and mean nestling mass were analysed in relation to lay date and habitat conditions in an alpine population of the migratory Northern WheatearOenanthe oenanthecollected over six consecutive breeding seasons in the Western Italian Alps. This open grassland species showed the lowest nest survival probability in years with an early onset of spring conditions. Within‐season, nest survival was highest when breeding late, at lower elevations, and when grass cover and grass height were higher. Both across‐ and within‐season, severe weather conditions may indirectly lead to higher early season nest failure rates by increasing predation risk. By contrast, mean nestling mass, and thus the quality of the fledglings, was lower when breeding late. This might be driven by a mismatch with the peak in food abundance. Breeding early is thus generally advantageous in terms of chick quality in our high‐elevation population, but reproductive success is limited by the risk of nest failure that is higher in early springs and early in the season. This trade‐off between breeding early and late may thus allow Northern Wheatears to maximize fitness under highly variable spring conditions. However, climate change may cause disruption to this trade‐off, and shifts in phenology could become a threat for migratory alpine birds that might not be able to keep track of advancing spring conditions.
Effects of adding quinoa flour on the composite wheat dough: a comprehensive analysis of the pasting, farinograph and rheological properties
Authors: Zhang Yu , Wang Xiaoxuan , Guan Xiao
Published: September 2022

Refined wheat breads are popular staples worldwide. Although they have desirable texture, they generally attribute to a high glycaemic index value. Adding whole‐grain flour to produce composite breads with both slower starch digestibility and ideal texture worth investigation. The present study investigated the pasting, farinographic and viscoelastic properties of the quinoa flour (QF)‐wheat flour (WF) composite dough. QF addition reduced the peak, final, breakdown and setback viscosities of the composite flour, indicating that starch gelatinisation was inhibited and retrogradation was slowed. QF addition increased G′ and G′′, while decreased tan δ (G′′/G′), exhibiting that the elasticity prevailed over viscosity for the composite dough. Farinograph analysis showed that when QF addition exceeded 20%, the stability time decreased and weakening degree increased sharply. Although creep‐recovery tests showed that 40% of QF addition exhibited the highest resistance to deformation, it disrupted the gluten network and brought negative effects on the composite dough. Taken these together, the composite wheat dough containing 20% of QF exhibited ideal rheological properties comprehensively. These results might be useful to develop and optimise mixed‐grain breads with lower glycaemic index.
Plastic response to disruptions: Significant redesign of supply chains
Authors: Hughes Molly M. , Zhou Zenan , Zinn Walter , Knemeyer A. Michael
Published: September 2022

A plastic response is a type of resilient response to disruption whereby a supply chain is significantly redesigned. This is in contrast to the most common responses to disruption emphasized in the extant resilience literature, in which restoration of a supply chain to its pre‐disruption state is typically the focus. Researching plastic responses is important because they differ greatly from restoration. A plastic response is a new way to operate, thus requiring implementation of major changes to the supply chain. Accordingly, a foundational premise is adopted to characterize a plastic response as (1) a significant redesign, (2) due to a pressing need, (3) requiring most or all of the following: acquisition of new skills, investment in new assets and leadership support, (4) a permanent new way to operate. Additionally, eight propositions are offered to serve as bases for further research. These relate to two fundamental issues: when are plastic responses most likely to be exercised and how to enable plastic responses. The propositions were developed through qualitative data analysis and informed by change management theory. The data were collected from in‐depth interviews with global corporations in a variety of industries. Theoretical contributions and managerial implications are offered at the end.
First identification of Nocardia seriolaeGapA adhesion function and its three B‐cell epitopes with cell‐binding activity
Authors: Guo Jiajing , Yue Xiaozhen , Chang Jiaojiao , Zhang Zhenyuan , Li Jinnian , Liu Xuelan
Published: September 2022

Fish nocardiosis mainly caused by Nocardia seriolae (N. seriolae) is a serious threat to aquaculture. Bacterial adhesion to host cells mediated by adhesin is an initial step of pathogenesis. But it is not clear whether glyceraldehyde‐3‐phosphate dehydrogenase (GapA) is an adhesin of N. seriolae. Here, recombinant GapA protein (rGapA) was prokaryotic expressed, and its role in the bacterial adhesion to Ctenopharyngodon idella kidney cells was investigated by indirect immunofluorescence, protein‐binding assay and adhesion inhibition assay. The results showed that an obvious green fluorescence was observed on the surface of the cells co‐incubated with rGapA protein; the cytomembrane proteins of the cells pretreated with rGapA could react with anti‐rGapA antibody; and the antibody significantly inhibited the adhesion ability of the bacteria. Subsequently, B‐cell linear epitopes of GapA protein were identified by using a immunoinformatics approach combined with peptide ELISA and Western blot for the first time. It was found that four predicted epitopes (Ep58‐69, Ep139‐150, Ep186‐197, Ep318‐329) could all react with anti‐rGapA antibody and obviously inhibit the immunoreactivity between rGapA and anti‐rGapA antibody, and they were confirmed as indeed B‐cell linear epitopes of the protein. Furthermore, flow cytometry analysis found the percentage of positive cells co‐incubated with FITC‐labelled epitope peptides (Ep139‐150, Ep186‐197, Ep318‐329) was significantly higher than those in the FITC‐labelled Ep58‐69, unrelated control peptide and cell control. Collectively, GapA is an adhesin of N. seriolae, and epitope peptides (Ep139‐150, Ep186‐197, Ep318‐329) possess cell‐binding activity, which are potential candidates for developing a multiple epitopes‐based adhesin vaccine against fish nocardiosis.