bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase‐ and state‐dependent modulation of breathing pattern by preBötzinger complex somatostatin expressing neurons
Authors: de Sousa Abreu Raquel P. , Bondarenko Evgeny , Feldman Jack L. 
Published: November 2021

AbstractAs neuronal subtypes are increasingly categorized, delineating their functional role is paramount. The preBötzinger complex (preBötC) subpopulation expressing the neuropeptide somatostatin (SST) is classified as mostly excitatory, inspiratory‐modulated and not rhythmogenic. We further characterized their phenotypic identity: 87% were glutamatergic and the balance were glycinergic and/or GABAergic. We then used optogenetics to investigate their modulatory role in both anaesthetized and freely moving mice. In anaesthetized mice, short photostimulation (100 ms) of preBötC SST+ neurons modulated breathing‐related variables in a combinatory phase‐ and state‐dependent manner; changes in inspiratory duration, inspiratory peak amplitude (Amp), and phase were different at higher (≥2.5 Hz) vs. lower (<2.5 Hz) breathing frequency (f). Moreover, we observed a biphasic effect of photostimulation during expiration that is probabilistic, that is photostimulation given at the same phase in consecutive cycles can evoke opposite responses (lengthening vs. shortening of the phase). These unexpected probabilistic state‐ and phase‐dependent responses to photostimulation exposed properties of the preBötC that were not predicted and cannot be readily accounted for in current models of preBötC pattern generation. In freely moving mice, prolonged photostimulation decreased f in normoxia, hypoxia or hypercapnia, and increased Amp and produced a phase advance, which was similar to the results in anaesthetized mice when f ≥ 2.5 Hz. We conclude that preBötC SST+ neurons are a key mediator of the extraordinary and essential lability of breathing pattern.Key points
PreBötzinger complex (preBötC) SST+ neurons, which modulate respiratory pattern but are not rhythmogenic, were transfected with channelrhodopsin to investigate phase‐ and state‐dependent modulation of breathing pattern in anaesthetized and freely behaving mice in normoxia, hypoxia and hypercapnia.
In anaesthetized mice, photostimulation during inspiration increased inspiratory duration and amplitude regardless of baseline f, yet the effects were more robust at higher f.
In anaesthetized mice with low f (<2.5 Hz), photostimulation during expiration evoked either phase advance or phase delay, whereas in anaesthetized mice with high f (≥2.5 Hz) and in freely behaving mice in normoxia, hypoxia or hypercapnia, photostimulation always evoked phase advance.
Phase‐ and state‐dependency is a function of overall breathing network excitability.
The f‐dependent probabilistic modulation of breathing pattern by preBötC SST+ neurons was unexpected, requiring reconsideration of current models of preBötC function, which neither predict nor can readily account for such responses.
High‐definition transcranial direct current stimulation modulates performance and alpha/beta parieto‐frontal connectivity serving fluid intelligence
Authors: Arif Yasra , Spooner Rachel K. , Heinrichs‐Graham Elizabeth , Wilson Tony W. 
Published: November 2021

AbstractFluid intelligence (Gƒ) includes logical reasoning abilities and is an essential component of normative cognition. Despite the broad consensus that parieto‐prefrontal connectivity is critical for Gƒ (e.g. the parieto‐frontal integration theory of intelligence, P‐FIT), the dynamics of such functional connectivity during logical reasoning remains poorly understood. Further, given the known importance of these brain regions for Gƒ, numerous studies have targeted one or both of these areas with non‐invasive stimulation with the goal of improving Gƒ, but to date there remains little consensus on the overall stimulation‐related effects. To examine this, we applied high‐definition direct current anodal stimulation to the left and right dorsolateral prefrontal cortex (DLPFC) of 24 healthy adults for 20 min in three separate sessions (sham, left, and right active). Following stimulation, participants completed a logical reasoning task during magnetoencephalography (MEG). Significant neural responses at the sensor‐level were imaged using a beamformer, and peak task‐induced activity was subjected to dynamic functional connectivity analyses to evaluate the impact of distinct stimulation montages on network activity. We found that participants responded faster following right DLPFC stimulationvs. sham. Moreover, our neural findings followed a similar trajectory of effects such that left parieto‐frontal connectivity decreased following right and left DLPFC stimulation compared to sham, with connectivity following right stimulation being significantly correlated with the faster reaction times. Importantly, our findings are consistent with P‐FIT, as well as theneural efficiency hypothesis(NEH) of intelligence. In sum, this study provides evidence for beneficial effects of right DLPFC stimulation on logical reasoning.Key pointsLogical reasoning is an indispensable component of fluid intelligence and involves multispectral oscillatory activity in parietal and frontal regions.Parieto‐frontal integration is well characterized in logical reasoning; however, its direct neural quantification and neuromodulation by brain stimulation remain poorly understood.High‐definition transcranial direct current stimulation of dorsolateral prefrontal cortex (DLPFC) had modulatory effects on task performance and neural interactions serving logical reasoning, with right stimulation showing beneficial effects.Right DLPFC stimulation led to a decrease in the response time (i.e. better task performance) and left parieto‐frontal connectivity with a marginal positive association between behavioural and neural metrics.Other modes of targeted stimulation of DLPFC (e.g. frequency‐specific) can be employed in future studies.
α2δ‐2 is required for depolarization‐induced suppression of excitation in Purkinje cells
Authors: Beeson Kathleen A. , Westbrook Gary L. , Schnell Eric 
Published: November 2021

Abstractα2δ proteins (CACNA2D1–4) are required for normal neurological function and contribute to membrane trafficking of voltage‐gated calcium channels, through which calcium entry initiates numerous physiological processes. However, it remains unclear how α2δ proteins influence calcium‐mediated signalling to control neuronal output. Using whole‐cell recordings of mouse Purkinje cells, we show that α2δ‐2 is required for functional coupling of postsynaptic voltage‐dependent calcium entry with calcium‐dependent effector mechanisms controlling two different outputs, depolarization‐induced suppression of excitation and spike afterhyperpolarization. Our findings indicate an important role for α2δ‐2 proteins in regulating functional postsynaptic calcium channel coupling in neurons, providing new context for understanding the effects of α2δ mutations on neuronal circuit function and presenting additional potential avenues to manipulate α2δ‐mediated signalling for therapeutic gain.Key points
Calcium influx, via voltage‐dependent calcium channels, drives numerous neuronal signalling processes with precision achieved in part by tight coupling between calcium entry and calcium‐dependent effectors.
α2δ proteins are important for neurological function and contribute to calcium channel membrane trafficking, although how α2δ proteins influence postsynaptic calcium‐dependent signalling is largely unexplored.
Here it is shown that loss of α2δ‐2 proteins disrupts functional calcium coupling to two different postsynaptic calcium‐dependent signals in mouse Purkinje cell neurons, retrograde endocannabinoid signalling and the action potential afterhyperpolarization.
The findings provide new insights into the control of calcium coupling as well as new roles for α2δ‐2 proteins in neurons.
Porphyry copper deposit formation in arcs: What are the odds?
Authors: Richards Jeremy P. 
Published: November 2021

AbstractArc magmas globally are H2O-Cl-S–rich and moderately oxidized (ΔFMQ = +1 to +2) relative to most other mantle-derived magmas (ΔFMQ ≤ 0). Their relatively high oxidation state limits the extent to which sulfide phases separate from the magma, which would otherwise tend to deplete the melt in chalcophile elements such as Cu (highly siderophile elements such as Au and especially platinum-group elements are depleted by even small amounts of sulfide segregation). As these magmas rise into the crust and begin to crystallize, they will reach volatile saturation, and a hydrous, saline, S-rich, moderately oxidized fluid is released, into which chalcophile and any remaining siderophile metals (as well as many other water-soluble elements) will strongly partition. This magmatic-hydrothermal fluid phase has the potential to form ore deposits (most commonly porphyry Cu ± Mo ± Au deposits) if its metal load is precipitated in economic concentrations, but there are many steps along the way that must be successfully negotiated before this can occur. This paper seeks to identify the main steps along the path from magma genesis to hydrothermal mineral precipitation that affect the chances of forming an ore deposit (defined as an economically mineable resource) and attempts to estimate the probability of achieving each step. The cumulative probability of forming a large porphyry Cu deposit at any given time in an arc magmatic system (i.e., a single batholith-linked volcanoplutonic complex) is estimated to be ~0.001%, and less than 1/10 of these deposits will be uplifted and exposed at shallow enough depths to mine economically (0.0001%). Continued uplift and erosion in active convergent tectonic regimes rapidly remove these upper-crustal deposits from the geological record, such that the probability of finding them in older arc systems decreases further with age, to the point that porphyry Cu deposits are almost nonexistent in Precambrian rocks.A key finding of this paper is that most volcanoplutonic arcs above subduction zones are prospective for porphyry ore formation, with probabilities only falling to low values at late stages of magmatic-hydrothermal fluid exsolution, focusing, and metal deposition. This is in part because of the high threshold required in terms of grade and tonnage for a deposit to be considered economic. Thus, the probability of forming a porphyry-type system in any given arc segment is relatively high, but the probability that it will be a large economic deposit is low, dictated to a large extent by mineral economics and metal prices.
Sex differences in mortality among binational cohort of people with chronic kidney disease: population based data linkage study
Authors: De La Mata Nicole L , Rosales Brenda , MacLeod Grace , Kelly Patrick J , Masson Philip , Morton Rachael L , Wyburn Kate , Webster Angela C 
Published: November 2021

AbstractObjectiveTo evaluate sex differences in mortality among people with kidney failure compared with the general population.DesignPopulation based cohort study using data linkage.SettingThe Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which includes all patients receiving kidney replacement therapy in Australia (1980-2019) and New Zealand (1988-2019). Data were linked to national death registers to determine deaths and their causes, with additional details obtained from ANZDATA.ParticipantsOf 82 844 people with kidney failure, 33 329 were female (40%) and 49 555 were male (60%); 49 376 deaths (20 099 in female patients; 29 277 in male patients) were recorded over a total of 536 602 person years of follow-up.Main outcome measuresRelative measures of survival, including standardised mortality ratios, relative survival, and years of life lost, using general population data to account for background mortality (adjusting for country, age, sex, and year). Estimates were stratified by dialysis modality (haemodialysis or peritoneal dialysis) and for the subpopulation of kidney transplant recipients.ResultsFew differences in outcomes were found between male and female patients with kidney failure. However, compared with the general population, female patients with kidney failure had greater excess all cause deaths than male patients (female patients: standardised mortality ratio 11.3, 95% confidence interval 11.2 to 11.5, expected deaths 1781, observed deaths 20 099; male patients: 6.9, 6.8 to 6.9, expected deaths 4272, observed deaths 29 277). The greatest difference was observed among younger patients and those who died from cardiovascular disease. Relative survival was also consistently lower in female patients, with adjusted excess mortality 11% higher (95% confidence interval 8% to 13%). Average years of life lost was 3.6 years (95% confidence interval 3.6 to 3.7) greater in female patients with kidney failure compared with male patients across all ages. No major differences were found in mortality by sex for haemodialysis or peritoneal dialysis. Kidney transplantation reduced but did not entirely remove the sex difference in excess mortality, with similar relative survival (P=0.83) and years of life lost difference reduced to 2.3 years (95% confidence interval 2.2 to 2.3) between female and male patients.ConclusionsCompared with the general population, female patients had greater excess deaths, worse relative survival, and more years of life lost than male patients, however kidney transplantation reduced these differences. Future research should investigate whether systematic differences exist in access to care and possible strategies to mitigate excess mortality among female patients.
Epidemiology, management and the associated burden of mental health illness, atopic and autoimmune conditions, and common infections in alopecia areata: protocol for an observational study series
Authors: Harries Matthew , Macbeth Abby E , Holmes Susan , Thompson Andrew R , Chiu Wing Sin , Gallardo William Romero , Messenger Andrew G , Tziotzios Christos , de Lusignan Simon 
Published: November 2021

IntroductionAlopecia areata (AA) is a common cause of immune-mediated non-scarring hair loss. Links between AA and common mental health, autoimmune and atopic conditions, and common infections have previously been described but remain incompletely elucidated and contemporary descriptions of the epidemiology of AA in the UK are lacking.Methods and analysisRetrospective study series using a large population-based cohort (5.2 million) from the Oxford Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database, exploring four themes: AA epidemiology, mental health comorbidities, autoimmune/atopic associations and common infections.In the epidemiology theme, we will describe the incidence and point prevalence of AA overall and by age, sex and sociodemographic factors. Healthcare utilisation (primary care visits and secondary care referrals) and treatments for AA will also be assessed. In the mental health theme, we will explore the prevalence and incidence of mental health conditions (anxiety, depressive episodes, recurrent depressive disorder, adjustment disorder, agoraphobia, self-harm and parasuicide) in people with AA compared with matched controls. We will also explore the mental health treatment patterns (medication and psychological interventions), time off work and unemployment rates. Within the autoimmune/atopic associations theme, we will examine the prevalence of atopic (atopic dermatitis, allergic rhinitis, asthma) and autoimmune conditions (Crohn’s disease, ulcerative colitis, coeliac disease, type 1 diabetes, Hashimoto’s thyroiditis, Graves’ disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus (SLE), polymyalgia rheumatica, Sjögren’s syndrome, psoriasis, vitiligo, multiple sclerosis, pernicious anaemia) in people with AA compared with matched controls. We will also estimate the incidence of new-onset atopic and autoimmune conditions after AA diagnosis. Within the common infections theme, we will examine the incidence of common infections (respiratory tract infection, pneumonia, acute bronchitis, influenza, skin infection, urinary tract infection, genital infections, gastrointestinal infection, herpes simplex, herpes zoster, meningitis, COVID-19) in people with AA compared with matched controls.Ethics and disseminationThe Health Research Authority decision tool classed this a study of usual practice, ethics approval was not required. Study approval was granted by the RCGP RSC Study Approval Committee. Results will be disseminated through peer-reviewed publications.Observational study registration numberNCT04239521.
High-risk factors for adverse pregnancy outcomes in systemic lupus erythaematosus: a retrospective study of a Chinese population
Authors: Jiang Meng , Chang Yanling , Wang You , Fu Qiong , Lin Sihan , Wu Jiayue , Di Wen 
Published: November 2021

ObjectiveTo clarify high-risk factors for adverse pregnancy outcomes (APOs) in systemic lupus erythaematosus (SLE).DesignA retrospective chart review study.SettingData were collected in a tertiary medical centre, Shanghai, China, from November 2010 to December 2018.ParticipantsA total of 513 pregnancies with SLE were retrospectively analysed. Twenty-seven patients who underwent artificial abortions due to personal reasons were excluded.Primary outcome measuresAPOs were primary outcomes, including foetal loss, premature birth, small for gestational age (SGA), asphyxia neonatorum, composite foetal APOs and hypertensive disorders of pregnancy (HDP). Multivariable logistic regression and Spearman correlation analysis were performed to determine the risk factors for APOs in SLE.ResultsRisk factors for foetal loss included prepregnancy hypertension, hypocomplementaemia-C3, anticardiolipin antibodies-IgM positivity and disease flares during pregnancy. Risk factors for premature birth included disease flares, use of immunosuppressive agents and HDP. Moreover, twin pregnancy, disease flares and HDP were risk factors for SGA, and prepregnancy hypertension was an independent risk factor for asphyxia neonatorum. Independent risk factors for composite foetal APOs included twin pregnancy, prepregnancy hypertension, disease flares during pregnancy, HDP, hypocomplementaemia-C3 and the use of immunosuppressive agents. Risk factors for SLE complicated with HDP included prepregnancy hypertension, renal disorders and thrombocytopaenia. Conversely, the use of aspirin was a protective factor against foetal loss and premature birth. The ds-DNA value had a low diagnostic value for APOs, whereas the extent of complement reduction may predict the incidence of composite foetal APOs and foetal loss. Proteinuria occurring in the first 20 gestational weeks may lead to APOs.ConclusionEstablished risk factors for each APO were identified in this study. Indicators with more predictive significance have been screened out from conventional indicators, which may help clinicians predict the pregnancy outcome of patients with SLE more accurately and minimise the incidence of APOs.
Vaccination against COVID-19 and society’s return to normality in England: a modelling study of impacts of different types of naturally acquired and vaccine-induced immunity
Authors: Song Fujian , Bachmann Max O 
Published: November 2021

ObjectivesTo project impacts of mass vaccination against COVID-19, and investigate possible impacts of different types of naturally acquired and vaccine-induced immunity on future dynamics of SARS-CoV-2 transmission from 2021 to 2024 in England.DesignDeterministic, compartmental, discrete-time Susceptible-Exposed-Infectious-Recovered (SEIR) modelling.ParticipantsPopulation in England.InterventionsMass vaccination programmes.Outcome measuresDaily and cumulative number of deaths from COVID-19.ResultsIf vaccine efficacy remains high (85%), the vaccine-induced sterilising immunity lasts ≥182 days, and the reinfectivity is greatly reduced (by ≥60%), annual mass vaccination programmes can prevent further COVID-19 outbreaks in England. Under optimistic scenarios, with annual revaccination programmes, the cumulative number of COVID-19 deaths is estimated to be from 130 000 to 150 000 by the end of 2024. However, the total number of COVID-19 deaths may be up to 431 000 by the end of 2024, under scenarios with compromised vaccine efficacy (62.5%), short duration of natural and vaccine immunity (365/182 days) and small reduction in reinfectivity (30%). Under the assumed scenarios, more frequent revaccinations are associated with smaller total numbers and lower peaks of daily deaths from COVID-19.ConclusionsUnder optimistic scenarios, mass immunisation using efficacious vaccines may enable society safely to return to normality. However, under plausible scenarios with low vaccine efficacy and short durability of immunity, COVID-19 could continue to cause recurrent waves of severe morbidity and mortality despite frequent vaccinations. It is crucial to monitor the vaccination effects in the real world, and to better understand characteristics of naturally acquired and vaccine-induced immunity against SARS-CoV-2.
Hospital management of major stroke types in Chinese adults: a population-based study of 20 000 hospitalised stroke cases
Authors: Qin Haiqiang , Turnbull Iain , Chen Yiping , Wright Neil , Liu Liping , Pei Pei , Tang Wei , Xiang Shengping , Guo Yu , Zhao Xingquan , Clarke Robert , Li Liming , Wang Yongjun , Chen Zhengming 
Published: November 2021

ObjectivesTo compare hospital treatments for major stroke types in Chinese adults by stroke pathological types, sex, age, calendar year, hospital tier, region and other factors.DesignCross-sectional analysis of medical records retrieved from 20 229 stroke cases in the China Kadoorie Biobank.SettingTen diverse areas (five urban, five rural) in China.ParticipantsFirst-incident stroke cases who were recruited during an 11-year follow-up of 0.5M participants in the China Kadoorie Biobank.MethodsElectronic copies of medical records of stroke cases were retrieved for clinical adjudication by local neurologists. Stroke cases were classified as ischaemic stroke (IS) (including lacunar infarction (LACI) and non-LACI (non-LACI)), intracerebral haemorrhage (ICH), subarachnoid haemorrhage (SAH) and unspecified stroke types.ResultsAmong 20 299 first-ever stroke cases, 17 306 (85%) had IS, 7123 had non-LACI, 6690 had LACI, 3493 had silent LACI, 2623 (13%) had ICH and 370 (2%) had SAH. Among IS cases, antiplatelet treatment was used by 64% (65% non-LACI, 66% LACI, 56% silent LACI), lipid-lowering by 50% (52% non-LACI, 53% LACI, 43% silent LACI) and blood pressure-lowering by ~42% of all IS types, with positive trends in the use of these treatments by calendar year and hospital tier. Among ICH cases, 53% used blood pressure-lowering and 10% used lipid-lowering treatments, respectively. In contrast, traditional Chinese medicines (TCMs) were used by 59% of IS (50% non-LACI, 62% LACI, 74% silent LACI), 38% of ICH and 30% of SAH cases, with positive trends by calendar year and by hospital tier.ConclusionsAmong IS cases, use of antiplatelet and lipid-lowering medications increased in recent years, but use of TCM still exceeded use of blood pressure-lowering treatment. In contrast, blood pressure-lowering treatment was widely used for ICH, but only half of all ICH cases used blood pressure-lowering treatment.