bluuebunny/crossref_metadata_2025 huggingface dataset:
Binocular, accommodative and oculomotor alterations in multiple sclerosis
Authors: Piñero David P. , Gil‐Casas Amparo , Molina‐Martín Ainhoa
Published: December 2022

Multiple sclerosis (MS) is an acquired demyelinating and inflammatory neurodegenerative disease affecting the central nervous system (CNS). Clinical and subclinical ocular disturbances occur in almost all patients with MS. Among them, oculomotor, accommodative and binocular alterations have been reported in MS. Our research group has conducted a complete analysis of the visual and oculomotor function in several researches with MS patients conducted in the last 4 years, obtaining a characterization of some visual aspects of the patient with MS. Concerning the binocular function, several alterations have been detected in MS patients, with divergence at near distance and stereopsis the most affected parameters. Likewise, MS patients with previous optic neuritis present worse binocular vision. Symptomatology compatible with convergence insufficiency measured with the CISS (Convergence Insufficiency Symptom Survey) is frequently reported by MS patients, but not supported by signs that show clear trend to esophoria at near. This discrepancy between the signs and symptoms could be due to the peculiarities of the CISS questionnaire, including items that are also related to the cognitive function and other ocular abnormalities.

Oculomotor alterations have been reported also in patients with multiple sclerosis (MS), especially saccadic dysfunctions. The indirect analysis of horizontal saccades with the Developmental Eye Movement (DEM) and King‐Devick tests shows that are affected by MS, with more level of alteration if there has been a previous episode of optic neuritis. Similar findings have been also reported by other authors using objective eye tracking or video‐oculographic systems. Specifically, the most reported saccadic alterations in advanced MS and clinically isolated syndrome (CIS) are saccadic dysmetry (41.7%) and impaired smooth pursuit (42.3%), which relates to prolonged saccadic latency, no matter if they have suffered or not optic neuritis or internuclear ophthalmoplegia (INO). An increase in saccadic latency has been even found in children with MS. Saccadic initiation time (SI time) and average inter‐saccadic intervals (ISI) are also higher in patients with MS. Furthermore, the first cause of acquired pendular nystagmus is MS.

Finally, macular sensitivity measured by microperimetry has been found to be altered in MS patients, especially in eyes with previous optic neuritis. Likewise, a fixational instability characterized also my microperimetry is present in MS patients with optic neuritis, with more increase of the vertical axis of the fixation area than of the horizontal. The ratio of the disease also affects the patient fixation pattern.
Asymptomatic subjects at high genetic risk of developing Alzheimer's disease: An OCT study
Authors: López‐Cuenca Inés
Published: December 2022

One of the major genetic risk factors for developing Alzheimer's disease (AD) is having a first‐degree family history of the disease. Approximately 40% of affected individuals have a family history of AD, and epidemiological studies indicate that the risk of AD in an individual with an affected first‐degree relative is four to ten times higher in cognitively healthy subjects. In addition, epidemiological studies have shown that transmission of the sporadic form of AD is both maternal and paternal, being the risk higher when it is the mother the affected patient, as it was associated with worse cognitive performance and a more predictable age of onset of the pathology. Among the possible explanatory genetic mechanisms, evidence of an inherited predisposition to cerebral metabolic reductions and atrophy in subjects with maternal family history suggests alterations in mitochondrial DNA (mtDNA), which is fully maternally inherited in humans.

ApoE mediates another important genetic risk factor and this gene has been implicated in the modulation of Aβ metabolism and aggregation. The allele of APOE, ɛ4, increases the risk of AD threefold for each ɛ4 allele, and the risk is higher among people of European ancestry. Furthermore, ApoE ɛ4 has been reported to affect magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) and cognitive biomarkers, and may have intrinsic effects on brain function. Likewise, ApoE ɛ4 + elevated levels of amyloid beta (Aβ) proteins are associated with episodic memory impairment and high risk for clinical AD, and ApoE ɛ4 carriers are also more vulnerable to environmental factors.

There is a clear relationship between retinal and brain changes in AD. In preclinical stages, retinal changes have been reported on optical coherence tomography (OCT), as well as the existence of associations between quadrant‐specific retinal nerve fibre layer thickness and brain regions analysed by 3 T MRI. In addition, both family history of the disease (FH+) and ApoE ɛ4 genotype (ApoE ɛ4+) potentiate each other, contributing to the thinning of the cortex in the hippocampal region. Likewiss, a direct correlation has been observed between the volumes of brain areas measured by magnetic resonance imaging (MRI) and the thickness of specific retina regions using OCT in nondemented older adults.

All of these observations support the value of the retina as a biomarker of AD. It is known that signs of dementia can appear decades before clinically detectable symptoms. For all these reasons, interest in finding new biomarkers of the disease has focused on the earliest stages of AD, seeking less invasive and less expensive diagnostic methods for early diagnosis of the disease. OCT, unlike other methods such as AB determination in CSF or PET, is a reliable and inexpensive non‐invasive diagnostic method that allows us to detect retinal changes in individuals at high risk for AD in preclinical stages of the disease, contributing to both early diagnosis and follow‐up of these individuals.
Neuroprotection in ophthalmology. Targets in the most frequent diseases. A clinician's point of view
Authors: Pastor Jose C. , Pastor‐Idoate Salvador , López‐Paniagua Marina , Para Marta , Blazquez Francisco , Murgui Esther , Coco‐Martín Rosa M.
Published: December 2022

Objectives: To briefly review the most frequent ocular diseases in which a neuroprotective treatment would be needed and to present the results of a translational research based on the neuroprotective capacities of allogeneic bone marrow‐derived mesenchymal stem cells (MSCs) in an ocular disease that currently lacks treatment, the non‐arteritic acute anterior ischemic optic neuropathy. (NA‐AION) considered as an infarct of the optic nerve head.

Methods: After extensive preclinical evaluation of safety in rabbits, a prospective, non‐randomized, phase II clinical trial (Eudra CT number 2016–003029‐40 and ClinicalTrials.gov NCT03173638) was approved. Five patients with acute unilateral NA‐AION diagnosed within the first 2 weeks after symptom onset were included. After informed consent, patients received an intravitreal injection of 0.05 ml containing 150 μl of isotonic medium composed of Ringer's lactate, 0.5% human albumin, and 5 mM glucose, with a cell concentration of 1.5 × 106 cells/ml. The injection was administered using a 25‐gauge needle via the pars plana after topical anaesthesia. Patients were followed on days 1, 7, 30, 90, 180 and 1 year after injection. Safety was defined as the absence of an inflammatory reaction. The best‐corrected visual acuity, visual evoked potentials (VEP) and retinal nerve fibre layer (RNFL) and ganglion cell layer (GCL) thicknesses were measured.

Results: No patients had signs of intraocular inflammation at any time. An epiretinal membrane (ERM) developed in one patient. One phakic patient had a retrolental aggregate that did not progress to cataract. Four patients had visual improvement and three had increased amplitudes on the VEP recordings after treatment. The RNFL and GCL thicknesses decreased significantly in parallel with the visible papillary atrophy that developed during the follow‐up period.

Conclusions: Despite development of an ERM in one patient and a possible cellular deposit in the retrolental space, the functional results are encouraging. A larger multicentre study of treated patients that includes a control group is currently running. The paracrine capacities of allergenic MSCs should be more extensively investigated in the clinic, taking advantage of their non‐immunogenicity, their ease of obtaining and their apparent safety.

Financial support: Funded by Strategic Action in Health of the Institute of Health Carlos III (PIC18/00018), the Department of Regional Health of the Castilla y Léon Government (GRS 1928/A/19), and the Department of Education of the Castilla y León Regional Government (Grant VA077P17).
autophagy response in chronic neuronal oxidative stress
Authors: Behl Christian
Published: December 2022

Age‐associated neurodegenerative diseases like Alzheimer's and Parkinson's disease (PD) but also glaucoma is generally accompanied by intracellular stress, malignant accumulations of dysfunctional proteins and a disturbance of the proteostasis. Over time adaptation and increased resilience are measures to make neurons more stable against age‐ and disease‐related challenges. The hippocampal cell line HT22 has been used to illustrate the adaptive ability in response to oxidative stress by enhancing autophagic activity via especially the process of BAG3‐mediated selective macroautophagy.

We extended the resistance protocol and generated a novel HT22 cell line that is resistant to thapsigargin, depleting intracellular Ca2+ stores and a potent inducer of ER stressor.

We observed a significantly increased LC3B‐II and p62 flux in thapsigargin‐resistant (TgR) compared with HT22‐WT | ells at both, basal and starved conditions. Intriguingly, when looking at the process of ER‐phagy manifold changes are occurring in TgR cells.

We suggest that the observed changes in autophagy‐related process, including ER‐phagy, may promote resistance against age‐related Ca2+ disturbance and Ca2+ stress in neuronal cells. Taken together, neuronal cell lines selected for a particular resistance allow molecular insights into neuronal adaptability.
Brain involvement in glaucoma: A new target in neuroprotection
Authors: Nucci Carlo
Published: December 2022

Glaucoma is one of the leading causes of blindness worldwide. The mechanisms underlying glaucomatous involvement of the central nervous system are still not completely known. It has been hypothesized that glaucomatous degeneration may be the result of anterograde transsynaptic neurodegeneration triggered by ganglion cells' death. However, it has been also postulated that in some cases it may be the consequence of neurodegenerative diseases of the central nervous system such as Alzheimer's' Disease. Autophagy and perfusion deficits have been also implicated in the etiopathogenesis of glaucoma. The introduction of new neuroimaging techniques may help to extend the knowledge about this disease, consent early diagnosis and could be a valuable tool for assessing the therapeutic efficacy of novel neuroprotective strategies.
ROCK inhibitors in glaucoma medical treatment
Authors: Oddone Francesco
Published: December 2022

Rho kinase inhibitors are a novel advancement in glaucoma medical treatment and have been recently approved for instruction in the market in fixed combination with the prostaglandin analogue Latanoprost. They have a novel mechanism of action based on their ability to improve humour aqueous outflow through the conventional trabecular meshwork pathway.

Rho family proteins are GTPases that localize in the intracellular side of plasma membrane and are activated by several plasma membrane signal receptors, including TGF‐β and hormones.

Activated Rho then activates Rho‐associated protein kinases which further transmit the stimulus to downstream effectors. The whole pathway is involved in several cellular activities, including actin cytoskeleton organization, cell adhesion and motility, proliferation and apoptosis, and remodelling of the ECM. ROCKs mediate pro‐fibrotic processes in many tissues and pathological conditions. In cultured human TM cells, exposure to a ROCK inhibitor caused retraction and rounding of cell bodies, as well as disruption of actin bundles and impaired focal adhesion formation. ROCKs have been associated when administered topically to a reduction in episcleral venous pressure that might contribute to their ocular hypotensive effects.

MERCURY‐3, was a prospective, randomized, double‐masked, active‐controlled study to assess the efficacy, safety, and tolerability of the ROCK inhibitor netarsudil 0.02% in fixed combination with latanoprost 0.005% compared with the fixed combination of bimatoprost 0.03%/timolol 0.5%.

The results of the study showed non inferiority of the netarsudil fixed combination despite a slightly worse local tolerability profile.

Current management approaches aim to reduce IOP but do not tackle the principal site of increased outflow resistance that is the TM. ROCK inhibition shows for the first time the ability for directly modulating the TM permeability and represents a new clinical treatment for glaucoma.
Bilateral recurrent choroidal neovascularization in AZOOR
Authors: Follonosa Alejandro
Published: December 2022

We present a case of acute zonal occult outer retinopathy (AZOOR) in a 61‐year‐old man who presented associated recurrent choroidal neovascularization as a complication in both eyes; he was managed with several intravitreal anti vascular endothelial growth factor (anti‐VEGF) injections in both eyes as well as with Prednisone and Methotrexate, which in improved the disease control.
brain mechanism of sight recovery
Authors: Röder Brigitte
Published: December 2022

Patients who were born with total bilateral cataracts and who were treated late in life show permanent deficits in visual acuity and other basic visual functions. Some higher visual functions are more (face identity processing, coherent motion processing) and other higher order visual functions (biological motion processing, visual exploration) are less impaired than expected from the visual acuity loss. Moreover, the integration of the late available visual input with the intact sensory inputs (hearing, touch) seems to be partially altered. The present talk will focus on new behavioural, electrophysiological and both functional and structural brain imaging results aiming to uncover the neural mechanisms of sight recovery in patients who had suffered from an extended period of blindness before they underwent cataract removal surgery.
novel insights into neuronal and vascular damage glaucoma
Authors: Di Polo Adriana
Published: December 2022

Despite decades of clinical and basic research, we still do not understand the factors that cause retinal ganglion cell death and loss of vision in glaucoma patients. This keynote lecture will provide insights into new mechanisms that lead to early neuronal and neurovascular dysregulation in glaucoma. Several pathological changes associated with retinal ganglion cell damage will be discussed including dendritic retraction and synapse loss, metabolic deficits, and loss of neurovascular coupling. The role of pericytes in retinal capillary function will be presented, including newly identified inter‐pericyte tunnelling nanotubes, and their impact on retinal ganglion cell viability. These new data will highlight therapeutic opportunities to alleviate key pathological processes and restore visual function in glaucoma and other optic neuropathies.
what can we learn from rare eye diseases
Authors: Bremond‐Gignac Dominique
Published: December 2022

Rare eye diseases are considered if the prevalence is lower than 1/2000 in the general population and are usually recognized in paediatric ophthalmologic practices. Even if not all ophthalmologists see these ocular diseases, the model mostly genetic, can be useful to treat other ocular anomalies in pathologies that are more common. We will expose new insights in congenital aniridia, a congenital panocular disorder characterized by complete or partial iris hypoplasia and foveal hypoplasia, resulting in nystagmus and reduced visual acuity. High‐resolution foveal imaging by spectral‐domain optical coherence tomography (SD‐OCT) may improve the diagnosis. Moreover, Leber congenital amaurosis is a new model for gene therapy and opens new therapeutic options. We will also provide update for congenital anterior segment malformations, vernal keratoconjunctivitis, albinism and OVCR in children.
How nurses use National Early Warning Score and Individual Early Warning Score to support their patient risk assessment practice: A fieldwork study
Authors: Langkjaer Caroline S. , Bundgaard Karin , Bunkenborg Gitte , Nielsen Pernille B. , Iversen Kasper K. , Bestle Morten H. , Bove Dorthe G.
Published: December 2022

Aim

To explore and describe how the National Early Warning Score (NEWS) and Individual Early Warning Score (I‐EWS) are used and how they support nurses' patient risk assessment practice.

Design

A qualitative observational fieldwork study drawing on ethnographical principles was performed in six hospitals in two regions of Denmark in 2019.

Methods

Data were generated from participant observations and informal interviews with 32 nurses across 15 different wards in the hospitals. A total of 180 h of participant observation was performed. The observations lasted between 1.5 and 8 h and were conducted during day or evening shifts.

Results

NEWS and I‐EWS supported nurses' observations of patients, providing useful knowledge for planning patient care, and prompting critical thinking. However, the risk assessment task was sometimes delegated to less experienced staff members, such as nursing students and healthcare assistants. The Early Warning Score (EWS) systems were often adapted by nurses according to contextual aspects, such as the culture of the speciality in which the nurses worked and their levels of competency. In some situations, I‐EWS had the effect of enhancing nurse autonomy and responsibility for decision‐making in relation to patient care.

Conclusions

EWS systems support nurses' patient risk assessment practice, providing useful information. I‐EWS makes it easier to factor the heterogeneity of patients and the clinical situation into the risk assessments. The delegation of risk assessment to other, less experienced staff members pose a risk to patient safety, which needs to be addressed in the ongoing debate regarding the shortage of nurses.

Impact

The findings of this study can help ward nurses, hospital managers and policymakers to develop and improve strategies for improved person‐centred nursing care.
Novel methodology for the evaluation of symptoms reported by patients with newly diagnosed atrial fibrillation: Application of natural language processing to electronic medical records data
Authors: Reynolds Matthew R. , Bunch Thomas Jared , Steinberg Benjamin A. , Ronk Christopher J. , Kim Hankyul , Wieloch Mattias , Lip Gregory Y. H.
Published: December 2022

Introduction

Understanding symptom patterns in atrial fibrillation (AF) can help in disease management. We report on the application of natural language processing (NLP) to electronic medical records (EMRs) to capture symptom reports in patients with newly diagnosed (incident) AF.

Methods and Results

This observational retrospective study included adult patients with an index diagnosis of incident AF during January 1, 2016 through June 30, 2018, in the Optum datasets. The baseline and follow‐up periods were 1 year before/after the index date, respectively. The primary objective was identification of the following predefined symptom reports: dyspnea or shortness of breath; syncope, presyncope, lightheadedness, or dizziness; chest pain; fatigue; and palpitations. In an exploratory analysis, the incidence rates of symptom reports and cardiovascular hospitalization were assessed in propensity‐matched patient cohorts with incident AF receiving first‐line dronedarone or sotalol. Among 30 447 patients with an index AF diagnosis, the NLP algorithm identified at least 1 predefined symptom in 9734 (31.9%) patients. The incidence rate of symptom reports was highest at 0–3 months post‐diagnosis and lower at >3–6 and >6–12 months (pre‐defined timepoints). Across all time periods, the most common symptoms were dyspnea or shortness of breath, followed by syncope, presyncope, lightheadedness, or dizziness. Similar temporal patterns of symptom reports were observed among patients with prescriptions for dronedarone or sotalol as first‐line treatment.

Conclusion

This study illustrates that NLP can be applied to EMR data to characterize symptom reports in patients with incident AF, and the potential for these methods to inform comparative effectiveness.
Leadless cardiac ventricular pacing using helix fixation: Step‐by‐step guide to implantation
Authors: Laczay Balint , Aguilera Jose , Cantillon Daniel J.
Published: December 2022

Introduction

Leadless cardiac pacemakers are an alternative modality to traditional transvenous pacemaker systems. Recently receiving Food and Drug Administration approval, the AVEIR VR leadless pacemaker system provides a helix based active fixation leadless pacemaker system. This step‐by‐step review will cover patient selection, preprocedural planning, device implantation technique, implant site evaluation, troubleshooting, short‐ and long‐term complications as well as future directions for leadless pacing.

Methods

We collected and reviewed cases from primary operators to provide a step‐by‐step review for implanters.

Results

Our paper provides a guide to patient selection, pre‐procedural planning, device im plantation technique, implant site evaluation, troubleshooting, short‐ and long‐term complications as well as future directions for leadless pacing.

Conclusion

The helix based active fixation leadless pacemaker system is a safe and efficacious way to provide pacing support to patients and provides an alternative to transvenous pacing systems. Our review provides a step‐by‐step guide to implantation.
Socioeconomic and sex inequalities in parent‐reported adolescent mental ill‐health: time trends in four British birth cohorts
Authors: McElroy Eoin , Tibber Marc , Fearon Pasco , Patalay Praveetha , Ploubidis George B.
Published: December 2022

Background

Studies using symptom‐based screeners have suggested that mental ill‐health has increased in adolescents in recent decades, however, few studies have tested the equivalence of their instruments, which is critical for inferring changes in prevalence. In addition, little research has explored whether socioeconomic position (SEP) and sex inequalities in adolescent mental health have changed over time.

Methods

Using structural equation modelling, we explored SEP and sex differences in harmonised parent reports of emotional and behavioural problems, using data from four UK birth cohorts: the 1958 National Child Development Study (NCDS'58; n = 10,868), the 1970 British Cohort Study (BCS'70; n = 8,242), the 1991–92 Avon Longitudinal Study of Parents and Children (ALSPAC'91; n = 5,389), and the 2000–01 Millennium Cohort Study (MCS'01; n = 9,338).

Results

Compared with the two earliest cohorts, members of MCS'01 had higher latent mean scores on emotional problems (both sexes), and lower scores on behavioural problems (females only). The associations between four indicators of SEP and emotional problems were strongest in MCS'01, with housing tenure having the strongest association. All four SEP indicators were associated with behavioural problems in each cohort, with housing tenure again more strongly associated with problems in the MCS'01. Mediation analyses suggested that the increase in emotional problems occurred despite broadly improving socioeconomic conditions.

Conclusions

Our findings suggest that parent reports of adolescent emotional problems, but not behavioural problems, have risen in recent generations and this trend is not solely due to reporting styles. A failure to address widening social inequalities may result in further increases in mental ill‐health amongst disadvantaged young people.
A cross‐sectional study reveals a chronic low‐grade inflammation in achalasia
Authors: Ma Li‐Yun , Liu Zu‐Qiang , Chen Wei‐Feng , Yao Lu , Zhong Yun‐Shi , Zhang Yi‐Qun , Ma Li‐Li , Qin Wen‐Zhen , Hu Jian‐Wei , Cai Ming‐Yan , Zhang Zhen , Lin Sheng‐Li , Hu Hao , Zhou Ping‐Hong , Li Quan‐Lin
Published: December 2022

Background and Aim

Immune‐mediated neuroinflammation has been proposed to underlie the loss of lower esophageal sphincter (LES) myenteric neurons in achalasia. However, the immune status and key pathogenic immune subpopulations remain unclear. This study aims to evaluate the inflammatory status of patients with achalasia and their correlation with clinical characteristics, and further explore the key pathogenic subpopulations.

Methods

We investigated the complete blood cell count and inflammatory markers in a large population of patients with achalasia (n = 341) and healthy controls (n = 80). The subpopulations of lymphocytes were analyzed by flow cytometry. Immunofluorescence was used to determine immune cell infiltration in the LES. Transcriptome changes of the key subpopulation were determined by RNA sequencing analysis.

Results

NLR, MLR, CRP, globulin, IL‐6 and IL‐10 were significantly elevated in patients with achalasia. MLR and globulin were positively correlated with disease duration. The absolute count and percentage of CD8+ T cells in peripheral blood and its infiltration around ganglion in the LES were significantly increased in achalasia. Transcriptome analysis indicated that CD8+ T cells were activated and proliferative. In addition to multiple inflammatory pathways, regulation of neuroinflammatory response pathway was also significantly up‐regulated in achalasia. GSEA analysis revealed a close association with autoimmune diseases.

Conclusions

Patients with achalasia suffered from chronic low‐grade inflammation with dysregulated immune cells and mediators associated with disease duration. CD8+ T cells might be the key pathogenic subpopulation of achalasia. Our results provide an important immune cell signature of the pathogenesis of achalasia.
Sorbitol induces flower bud formation via the MADS‐box transcription factor EjCAL in loquat
Authors: Xu Hong‐Xia , Meng Dong , Yang Qing , Chen Ting , Qi Meng , Li Xiao‐Ying , Ge Hang , Chen Jun‐Wei
Published: December 2022

Sorbitol is an important signaling molecule in fruit trees. Here, we observed that sorbitol increased during flower bud differentiation (FBD) in loquat (Eriobotrya japonica Lindl.). Transcriptomic analysis suggested that bud formation was associated with the expression of the MADS‐box transcription factor (TF) family gene, EjCAL. RNA fluorescence in situ hybridization showed that EjCAL was enriched in flower primordia but hardly detected in the shoot apical meristem. Heterologous expression of EjCAL in Nicotiana benthamiana plants resulted in early FBD. Yeast‐one‐hybrid analysis identified the ERF12 TF as a binding partner of the EjCAL promoter. Chromatin immunoprecipitation‐PCR confirmed that EjERF12 binds to the EjCAL promoter, and β‐glucuronidase activity assays indicated that EjERF12 regulates EjCAL expression. Spraying loquat trees with sorbitol promoted flower bud formation and was associated with increased expression of EjERF12 and EjCAL. Furthermore, we identified EjUF3GaT1 as a target gene of EjCAL and its expression was activated by EjCAL. Function characterization via overexpression and RNAi reveals that EjUF3GaT1 is a biosynthetic gene of flavonoid hyperoside. The concentration of the flavonoid hyperoside mirrored that of sorbitol during FBD and exogenous hyperoside treatment also promoted loquat bud formation. We identified a mechanism whereby EjCAL might regulate hyperoside biosynthesis and confirmed the involvement of EjCAL in flower bud formation in planta. Together, these results provide insight into bud formation in loquat and may be used in efforts to increase yield.
A culturally adapted parenting intervention for the Chilean context: Qualitative indicators of participant satisfaction and contextual and cultural relevance
Authors: Parra‐Cardona Rubén , Retamal Viviana Muñoz , Fajuri Paulina Peña , Rioseco Luz Cantizano , Mitchell Raúl Perry , Molina María Luisa Correa , Buenabad Nancy Amador
Published: December 2022

Parent training (PT) interventions constitute an empirically demonstrated alternative to promote effective parenting practices and prevent child behavioral and mental health problems. However, the dissemination of evidence‐based PT interventions across Latin America remains scarce. This qualitative study had the primary objective of evaluating the level of acceptability of a culturally adapted version of the PT intervention known as GenerationPMTO©, adapted for the Chilean context. According to qualitative reports provided by 24 Chilean caregivers exposed to the culturally adapted parenting intervention, the intervention was perceived by caregivers as useful for their parenting practices, as well as contextually and culturally relevant. Current qualitative findings indicate that the culturally adapted PT intervention holds promise for larger dissemination in the Chilean context.
The role of children's hospices in perinatal palliative care and advance care planning: The results of a national British survey
Authors: Tatterton Michael J. , Fisher Megan J. , Storton Helen , Walker Charlotte
Published: December 2022

Introduction

Perinatal palliative care services are increasingly available globally, offering a range of clinical and psychological support services to families during pregnancy, in the neonatal period and following the death of a baby with a life‐limiting or life‐threatening condition. Little is understood about the role of children's hospice care and how it contributes to effective perinatal palliative care.

Design

The study aims to answer the question “what is the role of children's hospices in the provision of perinatal palliative care and advance care planning in the United Kingdom?”

Methods

An electronic survey was sent to all 54 children's hospices in the United Kingdom between May and June 2022.

Results

Thirty hospices responded, representing 54% of the sector. All regions of all four counties are represented. Numbers of referrals to hospices for perinatal palliative care have increased significantly over the last 5 years. Hospices provide a range of services for families and babies, usually from the point of diagnosis or recognition of a life‐limiting or life‐threatening condition, underpinned with counseling and emotional support. Hospices worked with a range of professionals and services, most commonly fetal medicine and neonatal services. Advance care plans were an important element of effective perinatal palliative care, strengthening parent–professional and interprofessional relationships.

Conclusion

Children's hospice services play an important and growing role in the perinatal care of babies and families following the diagnosis or recognition of a life‐limiting or life‐threatening condition. The family‐centered approach to care, from a broad, biopsychosocial perspective means that hospices make a unique and meaningful contribution to both the clinical and psychological needs of families.

Clinical relevance

The family‐centered approach to care, from a broad, biopsychosocial perspective means that hospices make an important contribution to both the clinical needs of babies, and psychological needs of families antenatally, in the neonatal period and after death.
A pulse check on recent developments in time series econometrics
Authors: Chan Felix , Oxley Les
Published: December 2022

This article motivates and summarizes the contributions of the special issues on Recent Developments in Time Series Econometrics.
Hypertension treatment in patients with sleep apnea from the European Sleep Apnea Database (ESADA) cohort – towards precision medicine
Authors: Svedmyr Sven , Hedner Jan , Bonsignore Maria Rosaria , Lombardi Carolina , Parati Gianfranco , Ludka Ondrej , Zou Ding , Grote Ludger ,   the European Sleep Apnea Database (ESADA) study group (full collaborator list in E‐supplement)
Published: December 2022

We recruited 5,970 hypertensive patients with obstructive sleep apnea (OSA) on current antihypertensive treatment from the European Sleep Apnea Database (ESADA) cohort. The group was subdivided into those receiving monotherapy (n = 3,594) and those receiving dual combined therapy (n = 2,376). We studied how major OSA confounders like age, gender, and body mass index as well as the degree of sleep apnea modified office systolic and diastolic blood pressure. Beta‐blockers alone or in combination with a diuretic were compared with other antihypertensive drug classes. Monotherapy with beta‐blocker was associated with lower systolic blood pressure, particularly in non‐obese middle‐aged males with hypertension. Conversely, the combination of a beta‐blocker and a diuretic was associated with lower systolic and diastolic blood pressure in hypertensive patients with moderate–severe OSA. Systolic blood pressure was better controlled in female patients using this combined treatment. Our cross‐sectional data suggest that specific clinical characteristics and type of antihypertensive medication influence the degree of blood pressure control in hypertensive OSA patients. Controlled trials are warranted.
Direct and indirect genetic effects of a social supergene
Authors: Arsenault Samuel V. , Riba‐Grognuz Oksana , Shoemaker DeWayne , Hunt Brendan G. , Keller Laurent
Published: December 2022

Indirect genetic effects describe phenotypic variation that results from differences in the genotypic composition of social partners. Such effects represent heritable sources of environmental variation in eusocial organisms because individuals are typically reared by their siblings. In the fire antSolenopsis invicta, a social supergene exhibits striking indirect genetic effects on worker regulation of colony queen number, such that the genotypic composition of workers at the supergene determines whether colonies contain a single or multiple queens. We assessed the direct and indirect genetic effects of this supergene on gene expression in brains and abdominal tissues from laboratory‐reared workers and compared these with previously published data from field‐collected prereproductive queens. We found that direct genetic effects caused larger gene expression changes and were more consistent across tissue types and castes than indirect genetic effects. Indirect genetic effects influenced the expression of many loci but were generally restricted to the abdominal tissues. Further, indirect genetic effects were only detected when the genotypic composition of social partners differed throughout the development and adult life of focal workers, and were often only significant with relatively lenient statistical cutoffs. Our study provides insight into direct and indirect genetic effects of a social supergene on gene regulatory dynamics across tissues and castes in a complex society.
SUMOylation regulates pre‐mRNA splicing to overcome DNA damage in fungi
Authors: Jian Yunqing , Chen Xia , Sun Kewei , Liu Zunyong , Cheng Danni , Cao Jie , Liu Jianzhao , Cheng Xiaofei , Wu Liang , Zhang Feng , Luo Yuming , Hahn Matthias , Ma Zhonghua , Yin Yanni
Published: December 2022

Pathogenic fungi are subject to DNA damage stress derived from host immune responses during infection. Small ubiquitin‐like modifier (SUMO) modification and precursor (pre)‐mRNA splicing are both involved in DNA damage response (DDR). However, the mechanisms of how SUMOylation and splicing coordinated in DDR remain largely unknown.

Combining with biochemical analysis, RNA‐Seq method, and biological analysis, we report that SUMO pathway participates in DDR and virulence in Fusarium graminearum, a causal agent of Fusarium head blight of cereal crops world‐wide. Interestingly, a key transcription factor FgSR is SUMOylated upon DNA damage stress.

SUMOylation regulates FgSR nuclear‐cytoplasmic partitioning and its phosphorylation by FgMec1, and promotes its interaction with chromatin remodeling complex SWI/SNF for activating the expression of DDR‐related genes. Moreover, the SWI/SNF complex was found to further recruit splicing‐related NineTeen Complex, subsequently modulates pre‐mRNA splicing during DDR.

Our findings reveal a novel function of SUMOylation in DDR by regulating a transcription factor to orchestrate gene expression and pre‐mRNA splicing to overcome DNA damage during the infection of F. graminearum, which advances the understanding of the delicate regulation of DDR by SUMOylation in pathogenic fungi, and extends the knowledge of cooperation of SUMOylation and pre‐mRNA splicing in DDR in eukaryotes.
Above‐ and belowground interplay: Canopy CO2 uptake, carbon and nitrogen allocation and isotope fractionation along the plant‐ectomycorrhiza continuum
Authors: Scartazza Andrea , Sbrana Cristiana , D'Andrea Ettore , Matteucci Giorgio , Rezaie Negar , Lauteri Marco
Published: December 2022

In forests, mycorrhizal fungi regulate carbon (C) and nitrogen (N) dynamics. We evaluated the interplay among ectomycorrhizas (ECM), ecosystem C fluxes, tree productivity, C and N exchange and isotopic fractionation along the soil‐ECM‐plant continuum in a Mediterranean beech forest. From bud break to leaf shedding, we monitored: net ecosystem exchange (NEE, a measure of the net exchange of C between an ecosystem and the atmosphere), leaf area index, stem growth, N concentration, δ13C and δ15N in rhizosphere soil, ectomycorrhizal fine root tips (ERT), ECM‐free fine root portions (NCR) and leaves. Seasonal changes in ERT relative biomass were strictly related to NEE and mimicked those detected in the radial growth. The analysis of δ13C in ERT, leaves and NCR highlighted the impact of canopy photosynthesis on ERT development and an asynchronous seasonal C allocation strategy between ERT and NCR at the root tips level. Concerning N, δ15N of leaves was negatively related to that of ERT and dependent on seasonal 15N differences between ERT and NCR. Our results unravel a synchronous C allocation towards ERT and tree stem driven by the increasing NEE in spring‐early summer. Moreover, they highlighted a phenology‐dependent 15N fractionation during N transfer from ECM to their hosts. This evidence, obtained in mature beech trees under natural conditions, may improve the knowledge of Mediterranean forests functionality.
Dye Degradation and Sulfur Oxidation of Methyl Orange and Thiophenol via Newly Designed Nanocomposite GQDs/NiSe‐NiO Photocatalyst Under Homemade LED Light
Authors: Srivastava Shivangi , Yadav Rajesh K. , Pande Poorn Prakash , Singh Satyam , Chaubey Surabhi , Singh Pooja , Gupta Sarvesh Kumar , Gupta Shivani , Kim Tae Wu , Tiwary Dhanesh
Published: December 2022

Photocatalytic processes triggered by graphene‐based photocatalysts under solar light have sparked interest as a new sort of instrument for solar chemical synthesis. Herein we investigated self‐assembled graphene quantum dots (GQDs)/NiSe‐NiO composite photocatalyst for organic transformation as well as dye degradation. The synthesized GQDs/NiSe‐NiO composite photocatalyst has an excellent suitable band gap, high molar extinction coefficient, low toxicity and chemical/thermal stability. The GQDs/NiSe‐NiO composite photocatalyst emerges as a new standard for sulfur oxidation and dye degradation reactions under homemade LED light with high yield.
Using climate‐driven adaptive evolution to guide seed sourcing for restoration in a diverse North American herb‐shrub species
Authors: Johnson Richard C. , Love Stephen L. , Carver Daniel , Irish Brian M.
Published: December 2022

Seeds zones are bounded geographic areas to guide seed sourcing for landscape scale restoration. Yet seed zones based on plant adaptative traits are lacking for most restoration species. Sulfur‐flower buckwheat (Eriogonum umbellatum Torr) includes herbs, subshrubs, and shrubs adapted to a range of ecological regions within North America. Its widespread occurrence and diversity make it a suitable model species to explore seed zone development based on evolutionary plant adaptations. Within a common garden, 69 populations from diverse seed sources and 13 taxonomic varieties were evaluated for 17 phenological, morphological, and production traits in 2016 and 2017. Analyses of variance showed taxonomic varieties and seed source locations differed for all plant traits. Linear correlation revealed source locations with warmer mean temperature and more precipitation generally had later phenology, larger umbels, more leaf area, higher leaf dry weight, and more seed and shoot dry weight production. Canonical correlation strongly linked seed source climates at source locations with plant traits evaluated in the common garden, suggesting climate‐driven adaptive evolution. Canonical variates 1 and 2, explaining 60% of the variation, were used to develop regression models that predicted their values from climate variables across the study area. Using geographic information technology these were mapped into 12 seed zones representing 1.31 million km2 in the Western United States. These zones were designed to provide guidance to practitioners when sourcing sulfur‐flower buckwheat for restoration projects. We expect this methodology can be successfully applied to other species to develop seed zones based on adaptive evolution.
Environmental considerations in the European Union's pharmaceuticals legislation: Key instruments and their challenges in addressing global manufacturing supply chains
Authors: Kittery Anita , Miettinen Mirella
Published: December 2022

This article analyses how two key instruments of European Union pharmaceuticals legislation—good manufacturing practices and environmental risk assessment of pharmaceuticals—address known risks posed by the release of pharmaceuticals in the environment to human health and the environment and identifies the challenges that they face in regulating global manufacturing supply chains. The analysis reveals that these instruments fail to address the environmental challenges posed by pharmaceuticals within global manufacturing supply chains. Based on these findings, we propose to revise European pharmaceuticals legislation by expanding the scope and information requirements of both human and veterinary environmental risk assessment and increasing its weight in the risk–benefit analysis for human pharmaceuticals; by including direct environmental requirements for certain prioritized pharmaceuticals; and by integrating environmental considerations and related verification mechanisms into good manufacturing practices.
What drives local communities to engage in climate change mitigation activities? Examining the rural–urban divide
Authors: Zeigermann Ulrike , Kammerer Marlene , Böcher Michael
Published: December 2022

The National Climate Initiative (NKI) in Germany provides a strong incentive for local governments to apply for funding to engage in climate protection activities. Yet, the latest evaluation of the NKI confirms that there is a great disparity in the distribution of funding across regions. Taking this regional fragmentation as a starting point, we ask the following: How can we explain disparity in the amount of funding across counties and cities? We draw on climate policy literature pointing to the role of socioeconomic and political determinants and the settlement structure to answer this question. We study all 400 cities and counties to test hypotheses concerning disparity in the likelihood and amount of climate funding, using data from the German Ministry for the Environment and further regional statistics. Running different multilevel regression models, we show that local climate funding is more likely in cities and more urbanized counties than in rural counties with less population and oftentimes also with less young and educated people. We argue that despite the increasing number of local governments getting active in climate protection in Germany, there is important unused potential for climate change mitigation in rural counties. Therefore, we conclude by proposing a new research agenda focusing on climate change mitigation in rural areas.
Severe COVID‐19 patients show a dysregulation of the NLRP3 inflammasome in circulating neutrophils
Authors: Leal Vinicius N. C. , Andrade Milena M. S. , Teixeira Franciane M. E. , Cambui Raylane A. G. , Roa Mariela E. G. V. , Marra Letícia G. , Yamada Suemy M. , Alberca Ricardo W. , Gozzi‐Silva Sarah C. , Yendo Tatiana M. , Netto Lucas C. , Duarte Alberto J. S. , Sato Maria N. , Pontillo Alessandra
Published: December 2022

SARS‐CoV‐2 triggers inflammasome‐dependent release of pro‐inflammatory cytokine IL‐1β and pyroptosis, therefore, contributes to the huge inflammatory response observed in severe COVID‐19 patients. Less is known about the engagement of inflammasome in neutrophils, main players in tissue injury and severe infection. We studied the activation of the inflammasome in neutrophils from severe COVID‐19 patients and assessed its consequence in term of cells contribution to disease pathogenesis. We demonstrated that NLRP3 inflammasome is dramatically activated in neutrophils from severe COVID‐19 patients and that the specific inhibition of NLRP3 reverts neutrophils' activation. Next, the stimulation of severe patients' neutrophils with common NLRP3 stimuli was not able to further activate the inflammasome, possibly due to exhaustion or increased percentage of circulating immature neutrophils. Collectively, our results demonstrate that the NLRP3 inflammasome is hyperactivated in severe COVID‐19 neutrophils and its exhaustion may be responsible for the increased susceptibility to subsequent (and possibly lethal) infections. Our findings thus include a novel piece in the complex puzzle of COVID‐19 pathogenesis.
Mass spectrometry in sports drug testing—Analytical approaches and the athletes' exposome
Authors: Thevis Mario , Görgens Christian , Guddat Sven , Thomas Andreas , Geyer Hans
Published: December 2022

Test methods in anti‐doping, most of which rely on the most modern mass spectrometric instrumentation, undergo continuous optimization in order to accommodate growing demands as to comprehensiveness, sensitivity, retrospectivity, cost‐effectiveness, turnaround times, etc. While developing and improving analytical approaches is vital for appropriate sports drug testing programs, the combination of today's excellent analytical potential and the inevitable exposure of humans to complex environmental factors, specifically chemicals and drugs at the lowest levels, has necessitated dedicated research, particularly into the elite athlete's exposome. Being subjected to routine doping controls, athletes frequently undergo blood and/or urine tests for a plethora of drugs, chemicals, corresponding metabolic products, and various biomarkers. Due to the applicable anti‐doping regulations, the presence of prohibited substances in an athlete's organism can constitute an anti‐doping rule violation with severe consequences for the individual's career (in contrast to the general population), and frequently the question of whether the analytical data can assist in differentiating scenarios of ‘doping’ from ‘contamination through inadvertent exposure’ is raised. Hence, investigations into the athlete's exposome and how to distinguish between deliberate drug use and potential exposure scenarios have become a central topic of anti‐doping research, aiming at supporting and consolidating the balance between essential analytical performance characteristics of doping control test methods and the mandate of protecting the clean athlete by exploiting new strategies in sampling and analyzing specimens for sports drug‐testing purposes.
Identification of two novel HLA alleles, HLA‐A*03:344:02 and ‐DQB1*04:02:24 in Russian individuals
Authors: Loginova Maria , Smirnova Daria , Paramonov Igor , Belyaev Andrey
Published: December 2022

The novel HLA alleles HLA‐A*03:344:02 and ‐DQB1*04:02:24 have synonymous mutations.