bluuebunny/crossref_metadata_2025 huggingface dataset:
Using DNA to predict behaviour problems from preschool to adulthood
Authors: Gidziela Agnieszka , Rimfeld Kaili , Malanchini Margherita , Allegrini Andrea G. , McMillan Andrew , Selzam Saskia , Ronald Angelica , Viding Essi , von Stumm Sophie , Eley Thalia C. , Plomin Robert
Published: September 2021

Background

One goal of the DNA revolution is to predict problems in order to prevent them. We tested here if the prediction of behaviour problems from genome‐wide polygenic scores (GPS) can be improved by creating composites across ages and across raters and by using a multi‐GPS approach that includes GPS for adult psychiatric disorders as well as for childhood behaviour problems.

Method

Our sample included 3,065 genotyped unrelated individuals from the Twins Early Development Study who were assessed longitudinally for hyperactivity, conduct, emotional problems, and peer problems as rated by parents, teachers, and children themselves. GPS created from 15 genome‐wide association studies were used separately and jointly to test the prediction of behaviour problems composites (general behaviour problems, externalising, and internalising) across ages (from age 2 to 21) and across raters in penalised regression models. Based on the regression weights, we created multi‐trait GPS reflecting the best prediction of behaviour problems. We compared GPS prediction to twin heritability using the same sample and measures.

Results

Multi‐GPS prediction of behaviour problems increased from <2% of the variance for observed traits to up to 6% for cross‐age and cross‐rater composites. Twin study estimates of heritability, although to a lesser extent, mirrored patterns of multi‐GPS prediction as they increased from <40% to 83%.

Conclusions

The ability of GPS to predict behaviour problems can be improved by using multiple GPS, cross‐age composites and cross‐rater composites, although the effect sizes remain modest, up to 6%. Our approach can be used in any genotyped sample to create multi‐trait GPS predictors of behaviour problems that will be more predictive than polygenic scores based on a single age, rater, or GPS.
Report of a fulminant anti‐pan‐neurofascin‐associated neuropathy responsive to rituximab and bortezomib
Authors: Fels Miriam , Fisse Anna Lena , Schwake Carolin , Motte Jeremias , Athanasopoulos Diamantis , Grüter Thomas , Spenner Marie , Breuer Thomas , Starz Katharina , Heinrich David , Grond Martin , Keyvani Kathy , Appeltshauser Luise , Doppler Kathrin , Sommer Claudia , Ayzenberg Ilya , Schneider‐Gold Christiane , Gold Ralf , Pitarokoili Kalliopi , Labedi Adnan
Published: September 2021

Inflammatory neuropathies with pathogenic involvement of the nodes of Ranvier through autoantibodies have been increasingly characterized in the past years. The so‐called anti‐pan‐NF‐associated neuropathies caused by the simultaneous existence of anti‐Neurofascin‐186/‐140 and ‐155‐antibodies are extremely rare and cause life‐threatening symptoms. Therapeutic strategies are needed as symptoms may be life‐threatening and may not respond to standard first‐line CIDP treatment. We report a case of a 52‐year‐old male with a rare anti‐pan‐neurofascin (NF) (‐155, ‐186/‐140)‐associated neuropathy. The initial presentation was subacute with mild paresthesia leading to a fulminant “locked‐in”‐like syndrome requiring mechanical ventilation within the first eight weeks despite treatment with intravenous immunoglobulins. Nerve conduction studies revealed non‐excitable nerves with acute spontaneous activity in electromyography. High titers of anti‐Neurofascin‐155, −186/−140‐antibodies were detected in serum and cerebrospinal fluid. A combination of aggressive immunotherapy consisting of intravenous immunoglobulins, plasma exchange, rituximab and bortezomib resulted in clinical improvement with ambulation and non‐detectable anti‐neurofascin‐antibodies within the following 3 months. The follow‐up nerve conduction studies showed normalized amplitudes of the peripheral nerves with signs of reinnervation in electromyography. We conclude that an early aggressive immunotherapy consisting of a combination of rituximab and bortezomib could be considered as a therapeutic option for anti‐pan‐NF‐associated neuropathies.
Expedited Digital‐Analog Hybrid Method to Fabricate a 3D‐Printed Implant Overdenture
Authors: Scherer Michael D.
Published: September 2021

The present case report describes a technique to convert an interim mandibular complete dental prosthesis into a digitally designed and additively manufactured implant overdenture prosthesis. A patient had two dental implants placed, an interim complete denture, and a soft reline procedure completed. After implant osseointegration, existing healing abutments were removed, a functionally generated reline impression with polyvinyl siloxane impression material was made. Using an intraoral scanner, a 360‐degree optical scan was obtained of the relined interim prosthesis. A new prosthesis was digitally designed using the optical scan, additively manufactured, and housings picked‐up intraorally to create an implant‐retained overdenture.
Teen, Queer, and Asian: Lesbian, Gay, Bisexual, Transgender, Queer, Plus Asian American Students' Experiences in Schools
Authors: Gorse Michael Morgan , Bacolores John Paino , Cheung Jordan , De Pedro Kris Tunac
Published: September 2021

BACKGROUND

The experiences of youth with intersecting LGBTQ+ and Asian American (AA) identities have been largely unexplored. This study explored these experiences of LGBTQ+ AA California youth with mental health, school climate, and school victimization.

METHODS

Drawing from the 2016‐2017 California Healthy Kids Survey (N = 326,124), this study utilized secondary data analyses to examine mental health, school climate, and school victimization among students of specific AA ethnicities (eg, Cambodian, Hmong, Vietnamese) and LGBTQ+ identities. The participants in this study included 7th, 9th, and 11th graders from California public schools, with subsamples of lesbian or gay students (N = 13,291), bisexual students (N = 30,127), and transgender students (N = 7916).

RESULTS

The results indicated that Asian Indian, Cambodian, Hmong, Japanese, Korean, Laotian, and Other Asian LGBTQ+ students experienced more negative school climate and victimization compared to their Chinese, Filipino, Vietnamese, and white LGBTQ+ peers. For instance, 41.1% of Cambodian transgender students reported they were beaten up compared to 27.1% of white transgender students. Mental health differences between LGBTQ+ AA and LGBTQ+ white students were also found.

CONCLUSIONS

This study's findings can inform school administrators and teachers how to best support LGBTQ+ AA populations.
Evolutionary origin of a tetraploid Allium species on the Qinghai–Tibet Plateau
Authors: Li Minjie , Zheng Zeyu , Liu Juncheng , Yang Yongzhi , Ren Guangpeng , Ru Dafu , Zhang Shangzhe , Du Xin , Ma Tao , Milne Richard , Liu Jianquan
Published: September 2021

Extinct taxa may be detectable if they were ancestors to extant hybrid species, which retain their genetic signature. In this study, we combined phylogenomics, population genetics and fluorescence in situ hybridization (GISH and FISH) analyses to trace the origin of the alpine tetraploid Allium tetraploideum (2n = 4x = 32), one of the five known members in the subgenus Cyathophora. We found that A. tetraploideum was an obvious allotetrapoploid derived from ancestors including at least two closely related diploid species, A. farreri and A. cyathophorum, from which it differs by multiple ecological and genomic attributes. However, these two species cannot account for the full genome of A. tetraploideum, indicating that at least one extinct diploid is also involved in its ancestry. Furthermore, A. tetraploideum appears to have arisen via homoploid hybrid speciation (HHS) from two extinct allotetraploid parents, which derived in turn from the aforementioned diploids. Other modes of origin were possible, but all were even more complex and involved additional extinct ancestors. Our study together highlights how some polyploid species might have very complex origins, involving both HHS and polyploid speciation and also extinct ancestors.
An in vitro model for studies of attenuation of antibiotic‐inhibited growth of Aggregatibacter actinomycetemcomitans Y4 by polyamines
Authors: Wattimena Allan , Ganesan Sukirth M. , Kumar Purnima S. , Dabdoub Shareef M. , Walters John D.
Published: September 2021

Polyamines are ubiquitous polycationic molecules that are present in all prokaryotic and eukaryotic cells, and they serve as important modulators of cell growth, stress, and cell proliferation. Polyamines are present at high concentrations in the periodontal pocket and could potentially affect the stress response of periodontal bacteria to antibiotics. The effects of polyamines on inhibition of growth by amoxicillin (AMX), azithromycin (AZM), and doxycycline (DOX) were investigated with the Y4 strain of Aggregatibacter actinomycetemcomitans (Aa). Bacteria were grown in brain heart infusion broth under the following conditions: (1) Aa only, (2) Aa + polyamine mix (1 mM putrescine, 0.4 mM spermidine, and 0.4 mM spermine), (3) Aa + antibiotic, and (4) Aa + antibiotic + polyamines. Growth curve analysis, minimal inhibitory concentration determination, and transcriptomic studies were conducted. The presence of exogenous polyamines produced a small, but significant increase in Aa growth, and polyamines attenuated the inhibitory effects of AMX, AZM, and DOX on growth. Transcriptomic analysis revealed that polyamines upregulate expression of ribosomal biogenesis proteins and small subunits, attenuate the bacterial stress response to antibiotics, and modulate bacterial nutritional pathways in a manner that could potentially increase the virulence of Aa. In summary, the polyamine‐rich environment found in periodontal pockets appears to protect Aa and reduce its susceptibility to several antimicrobial agents in this in vitro model.
Wide‐field choroidal thickness and vascularity index in myopes and emmetropes
Authors: Yazdani Negareh , Ehsaei Asieh , Hoseini‐Yazdi Hosein , Shoeibi Nasser , Alonso‐Caneiro David , Collins Michael J
Published: September 2021

Purpose

To study regional variations in choroidal thickness (CT), luminal thickness and stromal thickness of the choroid, and choroidal vascularity index (CVI) in low myopic and emmetropic eyes using wide‐field optical coherence tomography (OCT).

Methods

Sixty‐nine healthy young adults between 20 and 38 years of age participated in this study, including 40 low myopes (mean ± SD spherical equivalent (MSE) refractive error: −3.00 ± 1.39 D, range: −6.00 to −0.62 D) and 29 emmetropes (MSE: −0.05 ± 0.09 D, range: −0.25 to +0.12 D). Wide‐field CT, luminal thickness, stromal thickness and CVI were measured across five eccentricities (fovea, parafovea, perifovea; near‐periphery and periphery) and four quadrants (nasal, temporal, inferior and superior), in vertical and horizontal meridians, while controlling for a range of extraneous factors potentially influencing the CT. Custom‐written software was used to segment and binarize the OCT images.

Results

Wide‐field CT, luminal thickness and stromal thickness, averaged across all participants, exhibited significant topographical variation, with the foveal (379 ± 8 µm, 200 ± 4 µm, 179 ± 4 µm, respectively) and peripheral (275 ± 8 µm, 161 ± 4 µm, 114 ± 4 µm, respectively) regions presenting the thickest and thinnest regions (all p < 0.001). Wide‐field CVI showed a progressively higher percentage (greater vascularity) with increasing eccentricity from the fovea towards the periphery (p < 0.001). Macular CT and stromal choroidal thickness were significantly thinner in myopes compared to emmetropes (p < 0.05). Myopes (55.7 ± 0.3%) showed a slightly higher CVI compared with emmetropes (54.4 ± 0.4%) (p < 0.05).

Conclusions

Low myopia in young adults was associated with significant choroidal thinning across the macular, but not extramacular regions, with this decrease in choroidal thickness mostly attributed to thinning in the stromal component of the choroid, rather than the luminal (vascular) component.
The wheat AGL6‐like MADS‐box gene is a master regulator for floral organ identity and a target for spikelet meristem development manipulation
Authors: Kong Xingchen , Wang Fang , Geng Shuaifeng , Guan Jiantao , Tao Shu , Jia Meiling , Sun Guoliang , Wang Zhenyu , Wang Ke , Ye Xingguo , Ma Jian , Liu Dengcai , Wei Yuming , Zheng Youliang , Fu Xiangdong , Mao Long , Lan Xiujin , Li Aili
Published: September 2021

The AGAMOUS‐LIKE6 (AGL6)‐like genes are ancient MADS‐box genes and are functionally studied in a few model plants. The knowledge of these genes in wheat remains limited. Here, by studying a ‘double homoeolog mutant’ of the AGL6 gene in tetraploid wheat, we showed that AGL6 was required for the development of all four whorls of floral organs with dosage‐dependent effect on floret fertility. Yeast two‐hybrid analyses detected interactions of AGL6 with all classes of MADS‐box proteins in the ABCDE model for floral organ development. AGL6 was found to interact with several additional proteins, including the G protein β and γ (DEP1) subunits. Analysis of the DEP1‐B mutant showed a significant reduction in spikelet number per spike in tetraploid wheat, while overexpression of AGL6 in common wheat increased the spikelet number per spike and hence the grain number per spike. RNA‐seq analysis identified the regulation of several meristem activity genes by AGL6, such as FUL2 and TaMADS55. Our work therefore extensively updated the wheat ABCDE model and proposed an alternative approach to improve wheat grain yield by manipulating the AGL6 gene.
Associations of cord metabolome and biochemical parameters with the neonatal deaths of cloned pigs
Authors: Ao Zheng , Wu Zhimin , Zhao Huaxing , Wu Zhenfang , Li Zicong
Published: September 2021

Neonatal cloned pigs generated via somatic cell nuclear transfer (SCNT) have high incidences of malformation and mortality. The mechanisms underlying the massive loss of cloned pig neonates remain unclear. We compared the cord serum metabolic profiles and biochemical indexes of SCNT‐derived piglets that died within 4 days (SCNT‐DW4), SCNT‐derived piglets that survived over 4 days (SCNT‐SO4) and artificial insemination (AI)‐generated piglets that survived over 4 days (AI‐SO4) to investigate the associations of serum metabolomics and biochemical indexes in umbilical cord (UC) sera at delivery with the neonatal loss of cloned pigs. Results showed that compared with SCNT‐SO4 and AI‐SO4 piglets, SCNT‐DW4 piglets had lower birth weight, placental indexes, placental vascularization scores, UC scores, vitality scores, serum glucose and levels but higher creatinine, urea nitrogen and uric acid levels in cord sera. Metabolomics analysis revealed alterations in lipid, glucose and purine metabolism in the cord sera of SCNT‐DW4 piglets. These results indicated that the disturbance of the cord serum metabolome might be associated with the low birth weight and malformations of cloned neonates. These effects were likely the consequences of the impaired placental morphology and function of SCNT‐derived piglets. This study provides helpful information regarding the potential mechanisms responsible for the neonatal death of cloned pigs and also offers an important basis for the design of effective strategies to improve the survival rate of these animals.
Concussion history in rugby union players is associated with depressed cerebrovascular reactivity and cognition
Authors: Owens Thomas S. , Calverley Thomas A. , Stacey Benjamin S. , Rose George , Fall Lewis , Tsukamoto Hayato , Jones Gareth , Corkill Robin , Tuaillon Edouard , Hirtz Christophe , Lehmann Sylvain , Marchi Nicola , Marley Christopher J. , Bailey Damian M.
Published: September 2021

Recurrent contact and concussion in rugby union remains a significant public health concern given the potential increased risk of neurodegeneration in later life. This study determined to what extent prior‐recurrent contact impacts molecular‐hemodynamic biomarkers underpinning cognition in current professional rugby union players with a history of concussion. Measurements were performed in 20 professional rugby union players with an average of 16 (interquartile range [IQR] 13–19) years playing history reporting 3 (IQR 1–4) concussions. They were compared to 17 sex‐age‐physical activity‐and education‐matched non‐contact controls with no prior history of self‐reported concussion. Venous blood was assayed directly for the ascorbate free radical (A•−electron paramagnetic resonance spectroscopy) nitric oxide metabolites (NO reductive ozone‐based chemiluminescence) and select biomarkers of neurovascular unit integrity (NVU chemiluminescence/ELISA). Middle cerebral artery blood flow velocity (MCAv doppler ultrasound) was employed to determine basal perfusion and cerebrovascular reactivity (CVR) to hyper/hypocapnia (). Cognition was assessed by neuropsychometric testing. Elevated systemic oxidative‐nitrosative stress was confirmed in the players through increased A•−(p < 0.001) and suppression of NO bioavailability (p < 0.001). This was accompanied by a lower CVR range (;p = 0.045) elevation in neurofilament light‐chain (p = 0.010) and frontotemporal impairments in immediate‐memory (p = 0.001) delayed‐recall (p = 0.048) and fine‐motor coordination (p < 0.001). Accelerated cognitive decline subsequent to prior‐recurrent contact and concussion history is associated with a free radical‐mediated suppression of CVR and neuronal injury providing important mechanistic insight that may help better inform clinical management.
Comparison of intraocular pressure in healthy brachycephalic and nonbrachycephalic cats using the Icare® TONOVET Plus rebound tonometer
Authors: Kerdchuchuen Kamolchanok , Samathayanon Kingkarn , Phientong Pitchapa , Chattraphirat Suprapha , Jaturakan Orapun , Tuntivanich Nalinee
Published: September 2021

Objective

To compare intraocular pressure using the Icare® TONOVET Plus rebound tonometer in healthy brachycephalic and nonbrachycephalic cats.

Animals studied

Both eyes of 78 healthy cats were investigated in this study. Cats were divided into two groups: brachycephalic (n = 39) and nonbrachycephalic (n = 39).

Procedures

Nose position and muzzle ratio were photographically recorded and analyzed. Physical and ophthalmic examinations were performed. Intraocular pressure was measured using the Icare® TONOVET Plus rebound tonometry instrument. Quantitative mean values were statistically compared using an unpairedt‐test at a significance level ofp < .05.

Results

Mean values of the nose position and muzzle ratio were significantly lower in the brachycephalic group (20.14 ± 5.43%, 9.61 ± 3.29%) compared with the nonbrachycephalic group (29.21 ± 4.30%, 13.97 ± 6.01%). The mean intraocular pressure for brachycephalic cats (15.76 ± 0.50 mmHg) was significantly lower (p < .001) than for nonbrachycephalic cats (18.77 ± 0.49 mmHg).

Conclusions

Intraocular pressure was significantly lower in brachycephalic cats using the Icare® TONOVET Plus rebound tonometer. Intraocular pressure values obtained in this study could be used as a guideline for measurements obtained using this tonometry device in healthy brachycephalic and nonbrachycephalic cats.
Survival and racing performance after surgical treatment of rib fractures in foals
Authors: Velloso Álvarez Ana , Sandow Cole B. , Rodgerson Dwayne H. , Spirito Michael A.
Published: September 2021

Objective

To evaluate the short and long‐term outcomes of foals treated surgically for fractured ribs and variables that may affect outcome.

Study design

Retrospective.

Animals

Seventy‐three equine neonates with surgically repaired fractured ribs.

Methods

Medical records were reviewed to include sex, breed, the side of thorax affected, number of ribs fractured, co‐morbidities directly associated with rib fracture, and surgical technique used. Short‐term outcome was defined as survival to discharge. Long‐term outcome was whether or not they started a race. Race records of maternal siblings were obtained for comparison.

Results

Seventy‐three neonates underwent surgery for fractured ribs. Fifty‐seven neonates (78%) survived to discharge from the hospital. Rib fractures were more commonly observed in colts and in the left hemithorax (61% and 57%, respectively). Sex, side affected, number of ribs fractured, co‐morbidities, number of ribs repaired, and surgical technique did not affect the short‐ or long‐term outcomes. Thirty‐five of 57 (61%) foals treated surgically for rib fractures that survived to discharge started a race compared to 173 of 257 (67%) of maternal siblings that raced.

Conclusions

Short‐ and long‐term outcome were not affected by co‐morbidities, surgical technique, or number of fractured ribs.

Clinical significance

Neonates with surgically repaired fractured ribs had a good prognosis for survival and and those that survived had a similar chances of starting a race compared to maternal siblings.
Differential signalling induced by α7 nicotinic acetylcholine receptors in hippocampal dentate gyrus in vitro and in vivo
Authors: Cheng Qing , Lamb Patricia , Stevanovic Korey , Bernstein Briana J. , Fry Sydney A. , Cushman Jesse D. , Yakel Jerrel L.
Published: September 2021

The activation of α7 nicotinic acetylcholine receptors (nAChRs) has been shown to improve hippocampus‐dependent learning and memory. α7 nAChRs are densely expressed among several different cell types in the hippocampus, with high Ca2+ permeability, although it is unclear if α7 nAChRs mobilize differential signalling mechanisms among distinct neuronal populations. To address this question, we compared α7 nAChR agonist‐induced responses (i.e. calcium and cAMP changes) between granule cells and GABAergic neurons in the hippocampal dentate gyrus both in vitro and in vivo. In cultured organotypic hippocampal slices, we observed robust intracellular calcium and cAMP increases in dentate granule cells upon activation of α7 nAChRs. In contrast, GABAergic interneurons displayed little change in either calcium or cAMP concentration after α7 nAChR activation, even though they displayed much larger α7 nAChR current responses than those of dentate granule cells. We found that this was due to smaller α7 nAChR‐induced Ca2+ rises in GABAergic interneurons. Thus, the regulation of the Ca2+ transients in different cell types resulted in differential subsequent intracellular signalling cascades and likely the ultimate outcome of α7 nAChR activation. Furthermore, we monitored neuronal activities of dentate granule cells and GABAergic interneurons in vivo via optic fibre photometry. We observed enhancement of neuronal activities after nicotine administration in dentate granule cells, but not in GABAergic neurons, which was absent in α7 nAChR‐deficient granule cells. In summary, we reveal a mechanism for α7 nAChR‐mediated increase of neuronal activity via cell type‐specific intracellular signalling pathways.

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Key points

α7 nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the central nervous system and regulate a variety of brain functions including learning and memory. Understanding the cellular signalling mechanisms of their activations among different neuronal populations is important for delineating their actions in cognitive function, and developing effective treatment strategies for cognitive deficits.

We report that α7 nAChR activation leads to Ca2+ and cAMP increases in granule cells (but not in GABAergic interneurons) in hippocampal dentate gyrus in vitro, a key region for pattern separation during learning.

We also found that nicotine enhanced granule cell (but not in GABAergic interneurons) activity in an α7 nAChR‐dependent manner via in vivo fibre photometry recording.

Based on our findings, we propose that differential responses to α7 nAChR activation between granule cells and GABAergic interneurons is responsible for the increase of excitation by α7 nAChR agonists in hippocampal circuits synergistically.
Measurement and Numerical Simulation of the Velocity Profile in the Thin Film of an Impinging Water Jet
Authors: Joppa Matthias , Bermuske Mike , Rüdiger Frank , Büttner Lars , Fröhlich Jochen , Czarske Juergen W.
Published: September 2021

Impinging circular free-surface water jets are used in challenging cooling and cleaning tasks. In order to develop simulation models for process optimization, validation data are required, which are currently not available. Therefore, the flow field of these jets is studied for the first time with the novel laser Doppler velocity profile sensor. The mean velocity field and fluctuations are measured within the stagnation and adjacent redirection region for radial coordinates up to three times the nozzle diameter. In the examined parameter range with jet velocities up to 17 m/s and nozzle diameters up to 5.2 mm, i.e., Reynolds numbers up to 69 500, thin films of a few hundred micrometers are formed, which hinder the measurement with common optical measuring systems. Based on the measurement results, a comparatively low-cost volume of fluid simulation model is developed and validated that presumes a relaminarized film flow. The profiles measured and the simulated flow show very good agreement. In the future, the simulation model provides a basis for process optimization and the innovative measurement technology used will prospectively provide further detailed insights into other flows with high velocity gradients.
Exploring Issues in Transnational Sport History
Authors: Lake Robert J. , Eaves Simon J.
Published: September 2021

Increasingly, sport has become an important lens through which to examine the historical influences of, and issues related to, transnational interactions and exchanges, yet the term “transnational” remains beset with disagreement regarding its precise meaning and definition. Commonly, transnational approaches to the historical study of sport provide opportunities to reach beyond “the nation,” whereby the nation–state is not positioned, necessarily, as the central category of analysis in discussions of cultural exchange between or across nations and borders. In such analyses, nonstate actors—essentially, those working outside of government influence—can move from the periphery to the center of focus. Challenging the dominant narrative of much historical research into globalization in sport that has tended to dwell on the negative, transnational approaches, as evidenced in this collection, offer new opportunities to consider positive, progressive, and co-operative aspects inherent to the connections and exchanges examined.
Splenic rupture as the presenting symptom in infective endocarditis: a rare and dangerous complication
Authors: Sen Gautam , Lewis Susan
Published: September 2021

Infective endocarditis remains a dangerous condition and carries a mortality risk of approximately 20%. Splenic rupture is a rare complication of endocarditis. A 60-year-old woman with a history of atrial fibrillation, mitral valve repair and severe mitral regurgitation was admitted with a fall and abdominal pain. Emergency laparotomy was performed leading to a diagnosis of splenic rupture, for which splenectomy was performed. Four months later, the patient represented with symptoms of a transient ischaemic attack. Transthoracic and transoesophageal echocardiogram confirmed a large vegetation on the anterior mitral valve leaflet. Treatment with antibiotics and re-do mitral valve surgery was performed. The cause of the initial splenic rupture was felt to have been secondary to undiagnosed infective endocarditis. It is imperative to consider endocarditis in a case of spontaneous splenic rupture particularly in high-risk patients such as those with previous valve surgery.
Accelerated balloon-retrograde transvenous obliteration (BRTO): an effective tool in the Arsenal against isolated gastric varices (IGV)
Authors: Deliwala Smit Sunil , Hussain Murtaza , Ponnapalli Anoosha , Igbinedion Samuel O , Bachuwa Ghassan , Bansal Anish
Published: September 2021

Gastric and oesophageal variceal bleeding poses high morbidity and mortality in cirrhosis. Amongst all types, isolated gastric varices (IGV) carry the highest propensity to bleed. Successful outcomes combine endoscopic and interventional radiology approaches using ligation, coils, glue or sclerosants. Transjugular intrahepatic portosystemic shunt success is only seen in a subset of patients, while balloon-retrograde transvenous obliteration (BRTO) has demonstrated high efficacy in preventing rebleeding and morbidity in patients with a myriad of anatomies and shunts. The American Association for the Study of Liver disease guidelines do not favour any particular modality; however, recent trials and meta-analyses support BRTO as the first-line therapy. Despite promising results, BRTO adoption is limited by procedural time, patient length-of-stay and equipment compatibilities hindering scalability in academic and community settings. To address these concerns, we present a successfully treated case of IGV with a revised technique called accelerated BRTO.
Cataract-causing G91del mutant destabilised βA3 heteromers formation linking with structural stability and cellular viability
Authors: Wang Huaxia , Tian Qing , Xu Jingjie , Xu Wanyue , Yao Ke , Chen Xiangjun
Published: September 2021

Background/aims

Congenital cataracts, which are genetically heterogeneous eye disorders, result in visual loss in childhood around the world. CRYBA1/BA3 serves as an abundant structural protein in the lens, and forms homomers and heteromers to maintain lens transparency. In previous study, we identified a common cataract-causing mutation, βA3-glycine at codon 91 (G91del) (c.271–273delGAG), which deleted a highly conserved G91del and led to perinuclear zonular cataract. In this study, we aimed to explore the underlying pathogenic mechanism of G91del mutation.

Methods

Protein purification, size-exclusion chromatography, spectroscopy and molecular dynamics simulation assays were used to investigate the effects on the heteromers formation and the protein structural properties of βA3-crystallin caused by G91del mutation. Intracellular βA3-G91del overexpression, MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide) and cell apoptosis were used to investigate the cellular functions of βA3-G91del.

Results

βA3-crystallin and βB2-crystallin could form heteromers, which have much more stable structures than βA3 homomers. Interestingly, βA3/βB2 heteromers improved their resistance against the thermal stress and the guanidine hydrochloride treatment. However, the pathogenic mutation βA3-G91del destroyed the interaction with βB2, and thereby decreased its structural stability as well as the resistance of thermal or chemical stress. What’s more, the βA3-G91del mutation induced cell apoptosis and escaped from the protection of βB2-crystallin.

Conclusions

βA3/βB2 heteromers play an indispensable role in maintaining lens transparency, while the βA3-G91del mutation destabilises heteromers formation with βB2-crystallin, impairs cellular viability and induces cellular apoptosis. These all might contribute to cataract development.
Diarrhoea and preadmission antibiotic exposure in COVID-19: a retrospective cohort study of 1153 hospitalised patients
Authors: Mateen Bilal Akhter , Samanta Sandip , Tullie Sebastian , O’Neill Sarah , Cargill Zillah , Kelly Gillian , Brennan Ewen , Patel Mehul , Al-Agil Mohammad , Galloway James , Teo James , Shawcross Debbie L , Kent Alexandra J , Hayee Bu'Hussain
Published: September 2021

Objective

The aims of this study were to describe community antibiotic prescribing patterns in individuals hospitalised with COVID-19, and to determine the association between experiencing diarrhoea, stratified by preadmission exposure to antibiotics, and mortality risk in this cohort.

Design/methods

Retrospective study of the index presentations of 1153 adult patients with COVID-19, admitted between 1 March 2020 and 29 June 2020 in a South London NHS Trust. Data on patients’ medical history (presence of diarrhoea, antibiotic use in the previous 14 days, comorbidities); demographics (age, ethnicity, and body mass index); and blood test results were extracted. Time to event modelling was used to determine the risk of mortality for patients with diarrhoea and/or exposure to antibiotics.

Results

19.2% of the cohort reported diarrhoea on presentation; these patients tended to be younger, and were less likely to have recent exposure to antibiotics (unadjusted OR 0.64, 95% CI 0.42 to 0.97). 19.1% of the cohort had a course of antibiotics in the 2 weeks preceding admission; this was associated with dementia (unadjusted OR 2.92, 95% CI 1.14 to 7.49). After adjusting for confounders, neither diarrhoea nor recent antibiotic exposure was associated with increased mortality risk. However, the absence of diarrhoea in the presence of recent antibiotic exposure was associated with a 30% increased risk of mortality.

Conclusion

Community antibiotic use in patients with COVID-19, prior to hospitalisation, is relatively common, and absence of diarrhoea in antibiotic-exposed patients may be associated with increased risk of mortality. However, it is unclear whether this represents a causal physiological relationship or residual confounding.
Remote evaluations of violence against women and girls interventions: a rapid scoping review of tools, ethics and safety
Authors: Seff Ilana , Vahedi Luissa , McNelly Samantha , Kormawa Elfriede , Stark Lindsay
Published: September 2021

Although programmes and policies targeting violence against women and girls (VAWG) have increased in the past decade, there is a paucity of evidence on the effectiveness of these interventions. To expand this evidence base, researchers increasingly employ remote data collection (RDC)—including online surveys, mobile applications and telephone interviews—in their evaluations. Although RDC allows for evaluations without in-person interactions—which are restricted during crises such as the COVID-19 pandemic— information about these methods is necessary to understand their potential usefulness and limitations. This scoping review examines remote evaluations of VAWG interventions to describe the landscape of RDC methods, reflect on safety and ethical considerations, and offer best practices for RDC in VAWG research. Fourteen studies met eligibility criteria, with seven, five, and two studies employing telephone interviews, online surveys, and mobile applications, respectively. Studies commonly stated that participants were asked to use a safe email or device, but the method for verifying such safety was rarely specified. Best practices around safety included creating a ‘quick escape’ button for online data collection to use when another individual was present, explaining to participants how to erase browsing history and application purchases, and asking participants to specify a safe time for researchers to call. Only eight studies established referral pathways for respondents as per best practice. None of the eligible studies took place in low/middle-income countries (LMICs) or humanitarian settings, likely reflecting the additional challenges to using RDC methods in lower resource settings. Findings were used to create a best practice checklist for programme evaluators and Institutional Review Boards using RDC for VAWG interventions. The authors found that opportunities exist for researchers to safely and effectively use RDC methodologies to gather VAWG data, but that further study is needed to gauge the feasibility of these methods in LMICs and humanitarian settings.
Implementation of a non-emergent medical transportation programme at an integrated health system
Authors: Lyons Patrick G , Ramsey Brett A , Welker Michael , Guinn Megan , Ernest Janice K , Kosydor Ali , Maddox Thomas M
Published: September 2021

Objectives

To implement a unified non-emergency medical transportation (NEMT) service across a large integrated healthcare delivery network.

Methods

We assessed needs among key organisational stakeholders, then reviewed proposals. We selected a single NEMT vendor best aligned with organisational priorities and implemented this solution system-wide.

Results

Our vendor’s hybrid approach combined rideshares with contracted vehicles able to serve patients with equipment and other needs. After 6195 rides in the first year, we observed shorter wait times and lower costs compared with our prior state.

Discussion

Essential lessons included (1) understanding user and patient needs, (2) obtaining complete, accurate and comprehensive baseline data and (3) adapting existing workflows—rather than designing de novo—whenever possible.

Conclusions

Our implementation of a single-vendor NEMT solution validates the need for NEMT at large healthcare organisations, geographical challenges to establishing NEMT organisation-wide, and the importance of baseline data and stakeholder engagement.
Association between serum phosphate and mortality in critically ill patients: a large retrospective cohort study
Authors: Chen Yang , Luo Mengdi , Xu Huange , Zhao Weiwei , He Qing
Published: September 2021

Objectives

This research aims to explore the impact of serum phosphate on the mortality of critically ill patients.

Design

A retrospective large cohort study.

Setting

Our data were extracted from a publicly accessible database named ‘Multiparameter Intelligent Monitoring in Intensive Care Database III’.

Participants

27 131 patients were included by clear definitions of selection and exclusion criteria.

Interventions

We used initial phosphate at admission as a design variable. Patients were divided into six groups with different serum phosphate levels and five groups at different intensive care unit (ICU) departments.

Primary and secondary outcomes

28-day and 90-day mortality were primary outcomes. All-cause mortality and length of stay ICU were secondary outcomes.

Results

Patients with very-high-normal serum phosphate, hypophosphataemia and hyperphosphataemia had worse outcomes. And the relationship between serum phosphate and the probability of 28-day or 90-day mortality had a linear relationship. After adjustment for potential confounders, hypophosphataemia and hyperphosphataemia were not significantly associated with 28-day or 90-day mortality. Nevertheless, at the medical ICU, hyperphosphataemia was associated with increased 28-day or 90-day mortality (HR=0.64, 95% CI 0.48 to 0.84, p=0.0017; HR=0.72, 95% CI 0.57 to 0.91, p=0.0067, respectively), using group 2 (≥2.5 mg/dL and <3.0 mg/dL) as the reference group.

Conclusions

Patients with very-high-normal serum phosphate also had worse outcomes, it might be necessary to re-evaluate the definitions of the normal reference range for serum phosphate. Hypophosphataemia and hyperphosphataemia are not the independent risk factors of 28-day or 90-day ICU mortality, which leads us to consider whether phosphate monitoring is not a necessary measure in critically ill patients. But hyperphosphataemia was associated with increased 28-day or 90-day mortality at the medical ICU, which emphasises the potential importance of early diagnosis and treatment of hyperphosphataemia for the patients who were admitted to the medical ICU.
Insight into the process of postpartum care utilisation and in-home support among vulnerable women in the Netherlands: an in-depth qualitative exploration
Authors: Laureij Lyzette T , van der Hulst Marije , Lagendijk Jacqueline , Been Jasper V , Ernst-Smelt Hiske E , Franx Arie , Lugtenberg Marjolein
Published: September 2021

Objective

To gain insight into the process of postpartum care utilisation and in-home support among vulnerable women.

Design, method, participants and setting

A qualitative interview study was conducted among 23 pregnant and postpartum vulnerable women in the Netherlands, following a grounded theory approach. Women were determined as vulnerable by their healthcare providers. Theoretical sampling of participants was applied and was alternated by data analysis to include information-rich cases until saturation was achieved.

Results

A conceptual framework of postpartum care utilisation was generated consisting of three phases: pregnancy, early postpartum period and late postpartum period. Within these phases, information provision, parenting self-efficacy and social network were identified as overarching themes. Perceived inadequate information on content of postpartum care posed a major barrier to forming realistic expectations during pregnancy and hindered its utilisation. Low self-efficacy facilitated postpartum care utilisation. All women experienced increased self-efficacy during and after postpartum care. Support from a social network influenced expectations regarding the added value of postpartum care during pregnancy, and lowered actual utilisation during the postpartum period. The costs of postpartum care and the role of the maternity care assistant acted as general barriers or facilitators influencing the three overarching themes and therefore postpartum care utilisation indirectly.

Conclusions

Our findings suggest that postpartum care utilisation among vulnerable women may be improved by considering the particular phase and relevant themes applying to individual women, and adapt care accordingly. We recommend to provide comprehensive, understandable information and to emphasise the gains of postpartum care in improving self-efficacy for vulnerable women. Moreover, involving a woman’s social network in postpartum care may add value to this care for this population.
Lag times in the publication of network meta-analyses: a survey
Authors: Tonin Fernanda S , Araujo Ariane G , Fachi Mariana M , Ferreira Vinicius L , Pontarolo Roberto , Fernandez-Llimos Fernando
Published: September 2021

Objective

We assessed the extent of lag times in the publication and indexing of network meta-analyses (NMAs).

Study design

This was a survey of published NMAs on drug interventions.

Setting

NMAs indexed in PubMed (searches updated in May 2020).

Primary and secondary outcome measures

Lag times were measured as the time between the last systematic search and the article submission, acceptance, online publication, indexing and Medical Subject Headings (MeSH) allocation dates. Time-to-event analyses were performed considering independent variables (geographical origin, Journal Impact Factor, Scopus CiteScore, open access status) (SPSS V.24, R/RStudio).

Results

We included 1245 NMAs. The median time from last search to article submission was 6.8 months (204 days (IQR 95–381)), and to publication was 11.6 months. Only 5% of authors updated their search after first submission. There is a very slightly decreasing historical trend of acceptance (rho=−0.087; p=0.010), online publication (rho=−0.080; p=0.008) and indexing (rho=−0.080; p=0.007) lag times. Journal Impact Factor influenced the MeSH allocation process, but not the other lag times. The comparison between open access versus subscription journals confirmed meaningless differences in acceptance, online publication and indexing lag times.

Conclusion

Efforts by authors to update their search before submission are needed to reduce evidence production time. Peer reviewers and editors should ensure authors’ compliance with NMA standards. The accuracy of these findings depends on the accuracy of the metadata used; as we evaluated only NMA on drug interventions, results may not be generalisable to all types of studies.
Patterns of sexual violence against adults and children during the COVID-19 pandemic in Kenya: a prospective cross-sectional study
Authors: Rockowitz Sarah , Stevens Laura M , Rockey James C , Smith Lisa L , Ritchie Jessica , Colloff Melissa F , Kanja Wangu , Cotton Jessica , Njoroge Dorothy , Kamau Catherine , Flowe Heather D
Published: September 2021

Objectives

This study examined patterns of sexual violence against adults and children in Kenya during the COVID-19 pandemic to inform sexual violence prevention, protection, and response efforts.

Design

A prospective cross-sectional research design was used with data collected from March to August 2020.

Setting

Kenya.

Participants

317 adults, 224 children.

Main measures

Perpetrator and survivor demographic data, characteristics of the assault.

Results

Bivariate analyses found that children were more likely than adults to be attacked during daytime (59% vs 44%, p<0.001) by a single perpetrator rather than multiple perpetrators (31% vs 13%, p<0.001) in a private as opposed to a public location (66% vs 45%, p<0.001) and by someone known to the child (76% vs 58%, p<0.001). Children were violated most often by neighbours (29%) and family members (20%), whereas adults were equally likely to be attacked by strangers (41%) and persons known to them (59%). These variables were entered as predictors into a logistic regression model that significantly predicted the age group of the survivor, χ2(5, n=541)=53.3, p<0.001.

Conclusions

Patterns of sexual violence against adult and child survivors during the COVID-19 pandemic are different, suggesting age-related measures are needed in national emergency plans to adequately address sexual violence during the pandemic and for future humanitarian crises.
Implementation of patient-centred care: which system-level determinants matter from a decision maker’s perspective? Results from a qualitative interview study across various health and social care organisations
Authors: Leidner Carmen , Vennedey Vera , Hillen Hendrik , Ansmann Lena , Stock Stephanie , Kuntz Ludwig , Pfaff Holger , Hower Kira Isabel
Published: September 2021

Objectives

The healthcare system is characterised by a high degree of complexity and involves various actors at different institutional levels and in different care contexts. To implement patient-centred care (PCC) successfully, a multidimensional consideration of influencing factors is required. Our qualitative study aims to identify system-level determinants of PCC implementation from the perspective of different health and social care organisations (HSCOs).

Design

A qualitative study using n=20 semistructured face-to-face interviews with n=24 participants was carried out between August 2017 and May 2018. Interview data were analysed based on concepts of qualitative content analysis using an inductive and deductive approach.

Setting and participants

Interviews were conducted with clinical and managerial decision makers from multiple HSCOs in the model region of Cologne, Germany. Participants were recruited via networks of practice partners and cold calling.

Results

This study identified various determinants on the system level that are associated with PCC implementation. Decision makers described external regulations as generating an economically controlled alignment of the healthcare system. The availability and qualification of staff resources and patient-related incentives of financial resources were identified as an eminent requirement for providers to deliver PCC. Participants considered the strict separation of financing and delivery of healthcare into inpatient and outpatient sectors to be a barrier to PCC. Interorganisational collaboration and information exchange were identified as facilitators of PCC, as they enable continuous patient care cycles.

Conclusion

The results showed the necessity of enforcing paradigm changes at the system level from disease-centredness to patient-centredness while aligning policy and reimbursement decisions directly with patient needs and values. A systematic, long-term planned strategy that extends across all organisations is lacking, rather each organisation seeks its own possibilities to implement PCC activities under external restrictions.

Trial registration number

DRKS00011925