bluuebunny/crossref_metadata_2025 huggingface dataset:
Monitoring air quality of Sharkia Governorate using remote sensing
Authors: Nagy Alaa , El-Zeiny Ahmed , Sowilem Mohamed , Moselhi Walaa , Elshaier Manal
Published: February 2024

Due to Sharkia population’s rapid growth, the crises of atmospheric pollutants are causing significant concern. These circumstances have positive and negative impacts on both environment and climate. This research aims to investigate and evaluate changes in land and air characteristics of the governorate using remotely sensed data from several satellites (Landsat, Aqua, Terra, and Sentinel-5P) in conjunction with geographic information system (GIS) techniques. Three multitemporal Landsat images were acquired in July 2002, 2012, and 2022, to monitor land use/land cover (LULC) changes during the past 20 years. In addition, aerosol optical depth (AOD) data were obtained daily over 2022, and Particulate Matter (PM2.5) was calculated and then averaged seasonally. Sentinel-5P was utilized for CO, NO2, and SO2 retrievals. Results showed that the governorate was continuously subjected to spatiotemporal changes in LULC during the whole study period. It was mainly occupied by vegetation with a total area of 3711.64, 3851.05, and 3794.59 km2 in 2002, 2012, and 2022, respectively. Seasonal means of PM2.5 followed this order: spring (77.59 µg/m3) > summer (50.76 µg/m3) > winter (49.29 µg/m3) > autumn (42.71 µg/m3). However, the winter season recorded the highest mean values for all gases, CO (946.58 µg/m3), NO2 (9.70 µg/m3), and SO2 (13.07 µg/m3). It was concluded that the southern region of the governorate is more vulnerable to environmental stresses, which can reduce biodiversity and ultimately affect the study area’s climate. In order to manage fragile ecosystems sustainably, this study recommends the creation of efficient land and air management information systems and regulations.
Dose Tapering and Discontinuation of Biologic DMARDs in Axial Spondyloarthritis: A Narrative Review (2023 SPARTAN Annual Meeting Proceedings)
Authors: Chaudhary Haseeb , Bittar Mohamad , Daoud Ansaam , Magrey Marina
Published: February 2024

Purpose of Review

Limited data is available for tapering or discontinuation of biologic therapy in patients with axSpA who are in disease remission. The current review concentrates on published studies regarding dose tapering or withdrawal of biologics in axSpA.

Recent Findings

Recent evidence in light of randomized controlled trials suggests that tapering of b-DMARDs is a feasible strategy to maintain remission or low disease activity in axSpA patients. TNF inhibitors were the studied biologics in most of these trials. The disease flare rates were comparable to those maintained on standard dose in most of these studies, although with variable tapering strategies and follow-up. Additionally, the duration of disease in remission prior to tapering, studied primary outcome, and flare definitions were heterogeneous. Female sex, HLA-B*27 negativity, high physician global score, and high CRP were negative predictors of successful tapering, but not consistently reported in all the trials. Although designed to address efficacy, there were no safety concerns with b-DMARD tapering. Withdrawal or complete discontinuation of biologics met with increased risk of flares compared to standard dosing.

Tapering of TNF inhibitors may be feasible in certain axSpA patients with an acceptable disease state; however, discontinuation is not currently recommended owing to increased risk of flare. Future studies with axSpA patients with longer remission duration prior to taper and different doses and types of b-DMARDs may provide more guidance.
Fungal Otitis Externa (Otomycosis) Associated with Aspergillus Flavus: A Case Image
Authors: MacDonald William W. , Wakely Paul E. , Kalmar John R. , Argyris Prokopios P.
Published: February 2024

A 48-year-old man presented with a chief complaint of intermittent right ear otorrhea of several-month duration, occasional otalgia and progressive unilateral hearing impairment. He also reported frequent episodes of headache and pressure in the sinuses and maxilla. Previous systemic treatment with antibiotics failed to alleviate the symptoms. A head/neck CT showed completely normal mastoid, middle ear and external auditory canal regions without any evidence of opacification or bone erosion. Otoscopic examination of the right ear disclosed aggregates of dried, brown, fibrillar material and debris occluding the external auditory canal and obstructing the otherwise intact tympanic membrane. Dilation of the external auditory canal or thickening of the tympanic membrane were not appreciated. The canal was debrided and the fibrillar material was placed in formalin. Histopathologic examination revealed numerous branching, septated fungal hyphae organized in densely-packed clusters. In other areas, the fungal hyphae abutted or were attached to lamellated collections of orthokeratin. As highlighted by GMS staining, the fungi were morphologically compatible with Aspergillus species. The clinicopathologic findings supported a diagnosis of fungal otitis externa, while the numerous anucleate squamous cells were compatible with colonization of an underlying, probably developing, cholesteatoma. Culture of material isolated from the external auditory canal confirmed the presence of Aspergillus flavus. In this illustrative case, we present the main clinical and microscopic characteristics of Aspergillus-related otomycosis developing in the setting of a tautochronous cholesteatoma.
New technologies in psychological intervention for adolescents with type I diabetes: a systematic review
Authors: Morales Paula , Valero-Moreno Selene , Pérez-Marín Marián
Published: February 2024

Type I diabetes mellitus (T1D) is a condition typically diagnosed during adolescence. The diagnosis of T1D, combined with the typical changes that occur during this developmental period, can have an impact on the psychopathology of adolescents. The aim of this study is to evaluate the effectiveness of a psychological intervention incorporating new technologies in managing psychopathological aspects among adolescents with T1D. A systematic search was carried out using the PRISMA method in the ProQuest and Web of Science databases, resulting in the screening of 209 studies, of which nine were included. Two evaluators independently and blindly selected and assessed the studies, demonstrating an excellent level of agreement. The age range of participants in the included studies varied from 12 to 21, with the common factor being a T1D diagnosis. The studies examined various variables, such as adherence to treatment, quality of life, and symptoms of depression and anxiety. Many of the studies indicated improvements in these aspects. However, it is crucial to note that the overall quality of the studies was low. Consequently, there is a need for further research on psychological interventions incorporating new technologies, and there is room for improvement in the design quality of such studies. While acknowledging the current limitations, the future of interventions for T1D is intricately linked to advancements in the development and integration of new technologies.
Lipoamide Attenuates Hypertensive Myocardial Hypertrophy Through PI3K/Akt-Mediated Nrf2 Signaling Pathway
Authors: Cao Hongjuan , Zhao Lina , Yuan Yao , Liao Chunyan , Zeng Weidan , Li Aiyue , Huang Quanfeng , Zhao Yueyao , Fan Yubing , Jiang Liu , Song Dandan , Li Sha , Zhang Bei
Published: February 2024

The process of myocardial hypertrophy in hypertension can lead to excessive activation of oxidative stress. Lipoamide (ALM) has significant antioxidant and anti-inflammatory effects. This study aimed to investigate the effects of ALM on hypertension-induced cardiac hypertrophy, as well as explore its underlying mechanisms. We evaluated the effects of ALM on spontaneously hypertensive rats and rat cardiomyocytes treated with Ang II. We found that ALM was not effective in lowering blood pressure in SHR, but it attenuated hypertension-mediated cardiac fibrosis, oxidative stress, inflammation, and hypertrophy in rats. After that, in cultured H9C2 cells stimulated with Ang II, ALM increased the expression of antioxidant proteins that were decreased in the Ang II group. ALM also alleviated cell hypertrophy and the accumulation of ROS, while LY294002 partially abrogated these effects. Collectively, these results demonstrate that ALM could alleviate oxidative stress in cardiac hypertrophy, potentially through the activation of the PI3K/Akt-mediated Nrf2 signaling pathway.

Graphical Abstract
DNA barcoding of Australian cereal cyst nematode populations with comments on likely origin and taxonomy (Tylenchoidea: Heterodera)
Authors: Huston Daniel C. , Khudhir Manda , Lewis John , Collins Sarah , Jain Akshita , Hodda Mike
Published: February 2024

A species of Heterodera has been known to parasitise cereals in Australia since the 1930s. It caused significant yield losses across Australia’s cereal growing regions until resistance breeding largely brought it under control, although it still occurs occasionally, especially in South and Western Australia. Australian cereal cyst nematode has long been considered to represent Heterodera avenae. However, in 2002 the name Heterodera australis was proposed for Australian cereal cyst nematode, as it could be distinguished from all non-Australian populations of H. avenae via biochemical and molecular methods. This new species proposal came with speculation that both H. avenae and H. australis might occur in Australia, and that H. australis might represent a native species. The name H. australis has generally not been accepted by Australian scientists, nor the notion that it is native. There remains some uncertainty as to the validity of H. australis and whether more than one species of cereal cyst nematode occur in Australia. Using a molecular barcoding approach (COI, 18S, ITS, 28S) we examined the species composition of cyst nematodes present in soil samples collected between 1989–2023 from Australian cereal growing regions. We find only one species of Heterodera parasitising cereals and, based on phylogenetic analyses, accept the validity of H. australis as the name best representative of this species. We also argue that, based on presently available evidence, H. australis is not native and was most likely introduced into Australia from Asia in the 1850s, rather than from Europe as has been generally assumed.
Predictive, preventive and personalised approach as a conceptual and technological innovation in primary and secondary care of inflammatory bowel disease benefiting affected individuals and populations
Authors: Arosa Laura , Camba-Gómez Miguel , Golubnitschaja Olga , Conde-Aranda Javier
Published: February 2024

Inflammatory bowel disease (IBD) is a global health burden which carries lifelong morbidity affecting all age groups in populations with the disease-specific peak of the age groups ranging between 15 and 35 years, which are of great economic importance for the society. An accelerating incidence of IBD is reported for newly industrialised countries, whereas stabilising incidence but increasing prevalence is typical for countries with a Westernised lifestyle, such as the European area and the USA. Although the aetiology of IBD is largely unknown, the interplay between the genetic, environmental, immunological, and microbial components is decisive for the disease manifestation, course, severity and individual outcomes. Contextually, the creation of an individualised patient profile is crucial for the cost-effective disease management in primary and secondary care of IBD. The proposed pathomechanisms include intestinal pathoflora and dysbiosis, chronic inflammation and mitochondrial impairments, amongst others, which collectively may reveal individual molecular signatures defining IBD subtypes and leading to clinical phenotypes, patient stratification and cost-effective protection against health-to-disease transition and treatments tailored to individualised patient profiles—all the pillars of an advanced 3PM approach. The paradigm change from reactive medical services to predictive diagnostics, cost-effective targeted prevention and treatments tailored to individualised patient profiles in overall IBD management holds a promise to meet patient needs in primary and secondary care, to increase the life-quality of affected individuals and to improve health economy in the area of IBD management. This article analyses current achievements and provides the roadmap for future developments in the area in the context of 3P medicine benefiting society at large.
Recognizing and detecting COVID-19 in chest X-ray images using constrained multi-view spectral clustering
Authors: El Hajjar Sally , Dornaika Fadi , Abdallah Fahed
Published: February 2024

Machine learning, particularly classification algorithms, has been widely employed for diagnosing COVID-19 cases. However, these methods typically rely on labeled datasets and analyze a single data view. With the vast amount of patient data available without labels, this paper addresses the novel challenge of unsupervised COVID-19 diagnosis. The goal is to harness the abundant data without labels effectively. In recent times, multi-view clustering has garnered considerable attention in the research community. Spectral clustering, known for its robust theoretical framework, is a key focus. However, traditional spectral clustering methods generate only nonlinear data projections, necessitating additional clustering steps. The quality of these post-processing steps can be influenced by various factors, such as initialization procedures and outliers. This paper introduces an enhanced version of the recent “Multiview Spectral Clustering via integrating Nonnegative Embedding and Spectral Embedding” method. While retaining the benefits of the original technique, the proposed model integrates two essential constraints: (1) a constraint for ensuring the consistent smoothness of the nonnegative embedding across all views and (2) an orthogonality constraint imposed on the columns of the nonnegative embedding matrix. The effectiveness of this approach is demonstrated using COVIDx datasets. Additionally, the method is evaluated on other image datasets to validate its suitability for this study.
Implementation of a Mentoring Program for Mentee-Mentor Satisfaction: A Longitudinal Pilot Study
Authors: David Michael C. , Pitman Melissa A.
Published: February 2024

Introduction

Mentoring is a unique educational workplace relationship that can support both the mentee and mentor’s skill, knowledge, social, and emotional needs. The primary aim of this longitudinal pilot study was to implement a formal mentoring program to assess its effect on mentee and mentor satisfaction.

Methods

Data was collected from two hospitals in New South Wales, Australia in late 2018 and early 2019. Junior doctors (mentees) and senior medical staff (mentors) were asked to complete pre-, mid-, and oost-program surveys, with questions relevant to mentee-mentor satisfaction, interactions, and participation. Mixed-effects ordinal logistic regression models were used to assess the program effect on mentee-mentor satisfaction, while Fishers’ exact test was used to evaluate mentee-mentor interactions and participation.

Results

Although there was evidence of upwards trends in the proportion of mentees and mentors who reported their satisfaction in the program as excellent and rated their work satisfaction as being very influenced by the program, both trends were statistically non-significant. While our study was likely underpowered, high participation rates provide promising evidence of the program’s acceptability and feasibility.

Conclusion

Though not reaching statistical significance, study results suggest that the implementation of a mentoring program has the potential to increase satisfaction levels among its participants, be they mentees or mentors. It is recommended that future studies recruit larger samples thereby having sufficient statistical power. Furthermore, causality should be explored in more detail through a multi-site randomized controlled trial design.
Open pit limit optimization considering the pumped storage benefit after mine closure: a case study
Authors: Liu Feiyue , Yang Ke , Yang Tianhong , Deng Wenxue , Li Hua , Yang Lingyue
Published: February 2024

Repurposing a closed mine as lower reservoir is a cost-effective way for the construction of pumped storage hydropower (PSH) plant. This method can eliminate the expenses of mine reclamation, reservoir construction, and land acquisition, resulting in significant cost savings and benefits for the PSH project, known as the PSH benefit. The construction of PSH plants within a closed mine is divided into surface mode and semi-underground mode in this paper. Through a general comparison of two in-situ cases, the finding highlight that the surface mode can achieve a larger potential installed capacity and lower construction cost. Furthermore, the PSH benefit is quantified and internalized as an economic parameter in the ultimate pit limit (UPL) optimization by allocating it into unit ore. Taken an undisclosed open-pit iron mine as example, the UPL is optimized by considering the PSH benefit. The internalized PSH benefit is calculated to be 6.59 CN¥/t when the installed capacity is 2000 MW, and ore amount within the optimized UPL is increased by 1.4%. The results indicated that the PSH benefit does influence the shape and size of UPL, but not significantly. Besides, converting several bottoms in a single open-pit into lower and upper reservoirs presents more challenges for UPL optimization, which further explorations is needed.
Neuroendokrine Tumoren der Lunge: State of the Art
Authors: Kiesewetter-Wiederkehr Barbara , Melhorn Philipp , Raderer Markus
Published: February 2024

Neuroendokrine Neoplasien (NEN) machen zirka ein Fünftel aller Lungenmalignome aus, meist liegt dabei das kleinzellige Bronchuskarzinom (SCLC) vor. Die gut differenzierten neuroendokrinen Tumoren (NET) der Lunge (auch als Lungenkarzinoide bezeichnet) sind hingegen selten. Die Prognose ist im Allgemeinen günstig, mit 10-Jahres-Überlebensraten von zirka 60 % für typische Karzinoide (NET G1) und 20 % für atypische Karzinoide (NET G2) im metastasierten Stadium. Klinisch gesehen können NET der Lunge – wenn auch selten – hormonelle Syndrome aufweisen (beispielsweise Karzinoidsyndrom oder Cushing-Syndrom). Interessanterweise haben diese Tumoren eine niedrige Mutationsrate, wobei am häufigsten Epigenetik-relevante Gene mutiert sind. Zu den Behandlungsstrategien von Lungen-NET gehören die chirurgische Resektion (als potenziell kurative Intervention im lokalisierten Stadium), ein Watch-and-wait-Vorgehen in ausgewählten Fällen und systemische Therapieoptionen. Everolimus ist die einzige zugelassene systemische Therapie und führte in der Placebo-kontrollierten Zulassungsstudie zu einer Verlängerung des progressionsfreien Überlebens (PFS; medianes PFS 9,2 Monate unter Everolimus versus 3,6 Monate in der Placebo-Kohorte). Trotz fehlender formeller Zulassung in dieser Indikation sind Somatostatinanaloga eine weitere von den Leitlinien empfohlene Therapie und können (wie die Peptidrezeptor-Radionuklidtherapie) eingesetzt werden, sofern ein Somatostatin-Rezeptorbesatz vorliegt. Weitere systemische Behandlungsoptionen sind vor allem Chemotherapien, z. B. Temozolomid- oder Oxaliplatin-basierte Kombinationen, während Immuntherapien und molekular gematchte Therapien bisher keine relevanten Effekte gezeigt haben.
Evolution and Development
Authors: Love Alan C.
Published: February 2024

The intersection of development and evolution has always harbored conceptual issues, but many of these are on display in contemporary evolutionary developmental biology (evo-devo). These issues include: (1) the precise constitution of evo-devo, with its focus on both the evolution of development and the developmental basis of evolution, and how it fits within evolutionary theory; (2) the nature of evo-devo model systems that comprise the material of comparative and experimental research; (3) the puzzle of how to understand the widely used notion of 'conserved mechanisms'; (4) the definition of evolutionary novelties and expectations for how to explain them; and (5) the demand of interdisciplinary collaboration that derives from investigating complex phenomena at key moments in the history of life, such as the fin-limb transition. This Element treats these conceptual issues with close attention to both empirical detail and scientific practice to offer new perspectives on evolution and development. This title is also available as Open Access on Cambridge Core.
The impact of military demobilisation on rising Irish migration to London, c.1750–1850
Authors: Crymble Adam
Published: February 2024

Irish soldiers demobilised in London after major eighteenth- and early nineteenth-century wars were an important but overlooked source of unintentional Irish migrants to the capital. Their migration was linked to the centralised military pension system, which meant that servicemen in English regiments had to present themselves for a medical examination at Chelsea or Greenwich hospitals — both in the London area. A lack of provision available to then get these often very disabled and wounded men back home to Ireland meant that many stayed semi-permanently or permanently in London, and their presence can be measured decades later in the 1841 census. This challenges current understandings about the Irish diaspora in Britain by highlighting the role of the government in shepherding Irish men across the Irish Sea.
Onboarding
Authors: Moser Klaus , Souček Roman , Galais Nathalie , Roth Colin
Published: February 2024

Die erfolgreiche Einführung und Integration neuer Mitarbeiterinnen und Mitarbeiter, auch als „Onboarding“ bezeichnet, ist für jede Organisation von zentraler Bedeutung und eine Kernaufgabe der Personalarbeit. Gelingt sie, dann werden nicht nur Fehler, Unfälle und Stress vermieden, sondern auch Lernprozesse initiiert sowie die Entwicklung von Commitment und Teamgeist der Mitarbeiterinnen und Mitarbeiter gefördert.
Dieses Buch macht deutlich, dass das Onboarding schon bei der Rekrutierung beginnt und je nach Zielgruppe ganz unterschiedliche Schwerpunkte gesetzt werden müssen. Als wesentliche Maßnahmen, die zu einer gelungenen Integration neuer Beschäftigter beitragen können, werden beschrieben: realistische Tätigkeitsvorschau, die Verwendung informeller Rekrutierungsmethoden, die Integration durch Führungskräfte und Teammitglieder, Schulungs- und Orientierungsprogramme, Paten- und Mentoringsysteme, Coaching und Supervision, Traineeprogramme, Teamentwicklung, der Einsatz von Social Media und finanzielle Anreize. Es werden jeweils Grundprinzipien, Wirkmechanismen, Evaluationsergebnisse und Fallbeispiele vorgestellt. Zudem werden deren Einordnung in die Organisationsstrategie, aber auch die Grenzen von Methoden zur Integration neuer Beschäftigter diskutiert.
Für die 2. Auflage wurden die Praxisbeispiele neu aufbereitet und erweitert, insbesondere die Ausführungen zu Migration und Social Media überarbeitet und die wissenschaftliche Literatur aktualisiert.
Frictional Aging of Single‐Asperity Nanoindentation Contacts in Quartz and Calcite
Authors: Badt Nir Z. , Goldsby David L. , Pharr George M. , Walker Christopher C.
Published: February 2024

The evolution of fault friction during the interseismic period affects the mechanics of a future earthquake on the same fault patch. Frictional aging has been previously tied to time‐dependent contact area growth through observations made on rock analogs. However, our understanding of the processes that control frictional aging is limited and is dependent on experiments that explore only numerous mechanisms. We conduct slide‐hold‐slide experiments with a dual‐axis nanoindenter on single‐crystal surfaces of quartz and calcite. Our results show that frictional aging in diamond‐quartz contacts is independent of time and contact area, in stark contradiction to past experiments done on quartz‐quartz contacts in rocks. Diamond‐calcite contacts show modest frictional aging, but still well below previous reported values from calcite‐calcite contacts. These results suggest that frictional aging of like‐on‐like minerals may be of chemical origin, as suggested in recent studies with atomic force microscopy and molecular dynamics simulations.
Impacts of North Atlantic Model Biases on Natural Decadal Climate Variability
Authors: Huo Wenjuan , Drews Annika , Martin Torge , Wahl Sebastian
Published: February 2024

Increasing the horizontal resolution of an ocean model is frequently seen as a way to reduce the model biases in the North Atlantic, but we are often limited by computational resources. Here, a two‐way nested ocean model configuration (VIKING10) that consists of a high‐resolution (1/10°) component and covers the northern North Atlantic, is embedded in a 1/2° ocean grid as part of the global chemistry‐climate model, FOCI (called FOCI‐VIKING10). This configuration yields a significantly improved path of the North Atlantic current (NAC), which here reduces the North Atlantic cold bias by ∼50%. Compared with the coarse‐resolution, non‐eddying model, the improved thermal state of upper ocean layers and surface heat fluxes in a historical simulation based on FOCI‐VIKING10 are beneficial for simulating the subdecadal North Atlantic Oscillation (NAO) variability (i.e., a period of 8 years). A northward drift of the NAO‐forced ocean thermal anomalies as seen in observations and the eddying FOCI‐VIKING10, provide a lagged ocean feedback to the NAO via changes in the net surface heat flux, leading to the NAO periodicity of 8 years. This lagged feedback and the 8 years variability of the NAO cannot be captured by the non‐eddying standard FOCI historical simulation. Furthermore, the argumentative responses of the North Atlantic to the 11‐year solar cycle are re‐examined in this study. The reported solar‐induced NAO‐like responses are confirmed in the 9‐member ensemble mean based on FOCI but with low robustness among individual members. A lagged NAO‐like response is only found in the nested eddying simulation but absent from the non‐eddying reference simulation, suggesting North Atlantic biases importantly limit climate model capability to realistically solar imprints in North Atlantic climate.
Simultaneous inhibition of PI3K and PAK in preclinical models of neurofibromatosis type 2-related schwannomatosis
Authors: Nagel Anna , Huegel Julianne , Petrilli Alejandra , Rosario Rosa , Victoria Berta , Hardin Haley M , Fernandez-Valle Cristina
Published: February 2024

Neurofibromatosis Type 2 (NF2)-related schwannomatosis is a genetic disorder that causes development of multiple types of nervous system tumors. The primary and diagnostic tumor type is bilateral vestibular schwannoma. There is no cure or drug therapy for NF2. Recommended treatments include surgical resection and radiation, both of which can leave patients with severe neurological deficits or increase the risk of future malignant tumors. Results of our previous pilot high-throughput drug screen identified phosphoinositide 3-kinase (PI3K) inhibitors as strong candidates based on loss of viability of mouse merlin-deficient Schwann cells (MD-SCs). Here we used novel human schwannoma model cells to conduct combination drug screens. We identified a class I PI3K inhibitor, pictilisib and p21 activated kinase (PAK) inhibitor, PF-3758309 as the top combination due to high synergy in cell viability assays. Both single and combination therapies significantly reduced growth of mouse MD-SCs in an orthotopic allograft mouse model. The inhibitor combination promoted cell cycle arrest and apoptosis in mouse merlin-deficient Schwann (MD-SCs) cells and cell cycle arrest in human MD-SCs. This study identifies the PI3K and PAK pathways as potential targets for combination drug treatment of NF2-related schwannomatosis.
Postnatal growth and neurodevelopment at 2 years’ corrected age in extremely low birthweight infants
Authors: Nyakotey David A. , Clarke Angelica M. , Cormack Barbara E. , Bloomfield Frank H. , Harding Jane E. ,   on behalf of the ProVIDe Study Group,   Steering Group, Bloomfield Frank H. , Jiang Yannan , Crowther Caroline A. , Cormack Barbara E. ,   Investigators, Bloomfield Frank , Broadbent Roland , McCaffrey Frances , Lynn Adrienne , Spencer Carole , Ellis Nicola , Graham Trish , Hewson Michael , Patel Harshad , Gibson Mel , Wilkes Natalie , Nair Arun , Harris Deborah , Streifler Nicola , Edwards Stephanie , Sisterson Rebecca , Akehurst Kimberly , Meyer Mike , de Monteverde Aiza , Yu Audrey , Tapnio Cristina , Alexander Tanith , Cormack Barbara , Huth Sabine , Liley Helen , Bates Suzanne , Jacobs Sue , Argus Brenda , Twitchell Emily
Published: February 2024

Background

Faltering postnatal growth in preterm babies is associated with adverse neurodevelopment. However, which growth reference is most helpful for predicting neurodevelopment is unknown. We examined associations between faltering growth and developmental delay in extremely low birthweight (ELBW) infants.

Methods

We categorized faltering growth (z-score decrease ≥0.8 for weight/length, >1 for head circumference) between birth, 4 weeks, 36 weeks’ postmenstrual age and 2 years’ corrected age using fetal (Fenton, UK-WHO and Olsen) and healthy preterm (INTERGROWTH-21st) references. Associations between faltering growth and developmental delay were examined using binary logistic regression and area under the receiver operating curve (AUC).

Results

In 327 infants, Olsen charts identified the highest prevalence of faltering growth (weight 37%, length 63%, head 45%). Agreement in classification was higher amongst fetal references (kappa coefficient, ĸ = 0.46–0.94) than between INTERGROWTH-21st and fetal references (ĸ = 0.10–0.81). Faltering growth in all measures between 4–36 weeks (odds ratio, OR 2.0–4.7) compared with other time intervals (OR 1.7–2.7) were more strongly associated with developmental delay, particularly motor delay (OR 2.0–4.7). All growth references were poorly predictive of developmental delay at 2 years (AUC ≤ 0.62).

Conclusions

Faltering postnatal growth in ELBW infants is associated with, but is poorly predictive of, developmental delay at 2 years.

Impact

In babies born preterm, different growth references result in wide variation in categorization of faltering postnatal growth.

Faltering growth in weight, length, and head circumference from 4 weeks to 36 weeks’ postmenstrual age are associated with developmental delay at 2 years’ corrected age, particularly motor delay.

However, postnatal growth is a poor predictor of later developmental delay in extremely low birthweight infants irrespective of the growth reference used.
Time-sensitive changes in the maternal brain and their influence on mother-child attachment
Authors: Nehls Susanne , Losse Elena , Enzensberger Christian , Frodl Thomas , Chechko Natalia
Published: February 2024

Pregnancy and the postpartum period are characterized by an increased neuroplasticity in the maternal brain. To explore the dynamics of postpartum changes in gray matter volume (GMV), magnetic resonance imaging was performed on 20 healthy postpartum women immediately after childbirth and at 3-week intervals for 12 postpartum weeks. The control group comprised 20 age-matched nulliparous women. The first 6 postpartum weeks (constituting the subacute postpartum period) are associated with decreasing progesterone levels and a massive restructuring in GMV, affecting the amygdala/hippocampus, the prefrontal/subgenual cortex, and the insula, which approach their sizes in nulliparous women only around weeks 3–6 postpartum. Based on the amygdala volume shortly after delivery, the maternal brain can be reliably distinguished from the nulliparous brain. Even 12 weeks after childbirth, the GMV in the dorsomedial prefrontal cortex, and the cortical thickness of the subgenual and lateral prefrontal cortices do not reach the pre-pregnancy levels. During this period, a volume decrease is seen in the cerebellum, the thalamus, and the dorsal striatum. A less hostile behavior toward the child at 6–12 weeks postpartum is predicted by the GMV change in the amygdala, the temporal pole, the olfactory gyrus, the anterior cingulate, the thalamus and the cerebellum in the same period. In summary, the restructuring of the maternal brain follows time-dependent trajectories. The fact that the volume changes persist at 12 weeks postpartum indicates that the maternal brain does not fully revert to pre-pregnancy physiology. Postpartum neuroplasticity suggests that these changes may be particularly significant in the regions important for parenting.
A literature review on prosthetically designed guided implant placement and the factors influencing dental implant success
Authors: Nulty Adam
Published: February 2024

This is an extensive review of the literature on prosthetically designed implant planning with particular regard to the factors influencing dental implant success. Electronic searches on PubMed and the Cochrane Central Register of Controlled Trials and manual searches were performed. The author selected the studies according to the inclusion and exclusion criteria. Meta-analysis of implant placement accuracy and a qualitative review of potential influencing factors were performed.

This literature review will explore prosthetically designed implant placement and its influence on dental implant success. By examining the factors that impact implant outcomes, this review aims to provide clinicians with a comprehensive understanding of the key considerations and best practices in achieving successful implant placements. Ultimately, this knowledge can contribute to enhancing patient care and the long-term success of dental implant treatments.
Predicting DNA structure using a deep learning method
Authors: Li Jinsen , Chiu Tsu-Pei , Rohs Remo
Published: February 2024

Understanding the mechanisms of protein-DNA binding is critical in comprehending gene regulation. Three-dimensional DNA structure, also described as DNA shape, plays a key role in these mechanisms. In this study, we present a deep learning-based method, Deep DNAshape, that fundamentally changes the current k-mer based high-throughput prediction of DNA shape features by accurately accounting for the influence of extended flanking regions, without the need for extensive molecular simulations or structural biology experiments. By using the Deep DNAshape method, DNA structural features can be predicted for any length and number of DNA sequences in a high-throughput manner, providing an understanding of the effects of flanking regions on DNA structure in a target region of a sequence. The Deep DNAshape method provides access to the influence of distant flanking regions on a region of interest. Our findings reveal that DNA shape readout mechanisms of a core target are quantitatively affected by flanking regions, including extended flanking regions, providing valuable insights into the detailed structural readout mechanisms of protein-DNA binding. Furthermore, when incorporated in machine learning models, the features generated by Deep DNAshape improve the model prediction accuracy. Collectively, Deep DNAshape can serve as versatile and powerful tool for diverse DNA structure-related studies.
Motility and tumor infiltration are key aspects of invariant natural killer T cell anti-tumor function
Authors: Tian Chenxi , Wang Yu , Su Miya , Huang Yuanyuan , Zhang Yuwei , Dou Jiaxiang , Zhao Changfeng , Cai Yuting , Pan Jun , Bai Shiyu , Wu Qielan , Chen Sanwei , Li Shuhang , Xie Di , Lv Rong , Chen Yusheng , Wang Yucai , Fu Sicheng , Zhang Huimin , Bai Li
Published: February 2024

Dysfunction of invariant natural killer T (iNKT) cells contributes to immune resistance of tumors. Most mechanistic studies focus on their static functional status before or after activation, not considering motility as an important characteristic for antigen scanning and thus anti-tumor capability. Here we show via intravital imaging, that impaired motility of iNKT cells and their exclusion from tumors both contribute to the diminished anti-tumor iNKT cell response. Mechanistically, CD1d, expressed on macrophages, interferes with tumor infiltration of iNKT cells and iNKT-DC interactions but does not influence their intratumoral motility. VCAM1, expressed by cancer cells, restricts iNKT cell motility and inhibits their antigen scanning and activation by DCs via reducing CDC42 expression. Blocking VCAM1-CD49d signaling improves motility and activation of intratumoral iNKT cells, and consequently augments their anti-tumor function. Interference with macrophage-iNKT cell interactions further enhances the anti-tumor capability of iNKT cells. Thus, our findings provide a direction to enhance the efficacy of iNKT cell-based immunotherapy via motility regulation.
CAR-T cell therapy targeting surface expression of TYRP1 to treat cutaneous and rare melanoma subtypes
Authors: Jilani Sameeha , Saco Justin D. , Mugarza Edurne , Pujol-Morcillo Aleida , Chokry Jeffrey , Ng Clement , Abril-Rodriguez Gabriel , Berger-Manerio David , Pant Ami , Hu Jane , Gupta Rubi , Vega-Crespo Agustin , Baselga-Carretero Ignacio , Chen Jia M. , Shin Daniel Sanghoon , Scumpia Philip , Radu Roxana A. , Chen Yvonne , Ribas Antoni , Puig-Saus Cristina
Published: February 2024

A major limitation to developing chimeric antigen receptor (CAR)-T cell therapies for solid tumors is identifying surface proteins highly expressed in tumors but not in normal tissues. Here, we identify Tyrosinase Related Protein 1 (TYRP1) as a CAR-T cell therapy target to treat patients with cutaneous and rare melanoma subtypes unresponsive to immune checkpoint blockade. TYRP1 is primarily located intracellularly in the melanosomes, with a small fraction being trafficked to the cell surface via vesicular transport. We develop a highly sensitive CAR-T cell therapy that detects surface TYRP1 in tumor cells with high TYRP1 overexpression and presents antitumor activity in vitro and in vivo in murine and patient-derived cutaneous, acral and uveal melanoma models. Furthermore, no systemic or off-tumor severe toxicities are observed in an immunocompetent murine model. The efficacy and safety profile of the TYRP1 CAR-T cell therapy supports the ongoing preparation of a phase I clinical trial.
Using the heme peroxidase APEX2 to probe intracellular H2O2 flux and diffusion
Authors: Eid Mohammad , Barayeu Uladzimir , Sulková Kateřina , Aranda-Vallejo Carla , Dick Tobias P.
Published: February 2024

Currently available genetically encoded H2O2 probes report on the thiol redox state of the probe, which means that they reflect the balance between probe thiol oxidation and reduction. Here we introduce the use of the engineered heme peroxidase APEX2 as a thiol-independent chemogenetic H2O2 probe that directly and irreversibly converts H2O2 molecules into either fluorescent or luminescent signals. We demonstrate sensitivity, specificity, and the ability to quantitate endogenous H2O2 turnover. We show how the probe can be used to detect changes in endogenous H2O2 generation and to assess the roles and relative contributions of endogenous H2O2 scavengers. Furthermore, APEX2 can be used to study H2O2 diffusion inside the cytosol. Finally, APEX2 reveals the impact of commonly used alkylating agents and cell lysis protocols on cellular H2O2 generation.
Mapping the global distribution of C4 vegetation using observations and optimality theory
Authors: Luo Xiangzhong , Zhou Haoran , Satriawan Tin W. , Tian Jiaqi , Zhao Ruiying , Keenan Trevor F. , Griffith Daniel M. , Sitch Stephen , Smith Nicholas G. , Still Christopher J.
Published: February 2024

Plants with the C4 photosynthesis pathway typically respond to climate change differently from more common C3-type plants, due to their distinct anatomical and biochemical characteristics. These different responses are expected to drive changes in global C4 and C3 vegetation distributions. However, current C4 vegetation distribution models may not predict this response as they do not capture multiple interacting factors and often lack observational constraints. Here, we used global observations of plant photosynthetic pathways, satellite remote sensing, and photosynthetic optimality theory to produce an observation-constrained global map of C4 vegetation. We find that global C4 vegetation coverage decreased from 17.7% to 17.1% of the land surface during 2001 to 2019. This was the net result of a reduction in C4 natural grass cover due to elevated CO2 favoring C3-type photosynthesis, and an increase in C4 crop cover, mainly from corn (maize) expansion. Using an emergent constraint approach, we estimated that C4 vegetation contributed 19.5% of global photosynthetic carbon assimilation, a value within the range of previous estimates (18–23%) but higher than the ensemble mean of dynamic global vegetation models (14 ± 13%; mean ± one standard deviation). Our study sheds insight on the critical and underappreciated role of C4 plants in the contemporary global carbon cycle.
Amyloid-β aggregates activate peripheral monocytes in mild cognitive impairment
Authors: Juul-Madsen Kristian , Parbo Peter , Ismail Rola , Ovesen Peter L. , Schmidt Vanessa , Madsen Lasse S. , Thyrsted Jacob , Gierl Sarah , Breum Mihaela , Larsen Agnete , Andersen Morten N. , Romero-Ramos Marina , Holm Christian K. , Andersen Gregers R. , Zhao Huaying , Schuck Peter , Nygaard Jens V. , Sutherland Duncan S. , Eskildsen Simon F. , Willnow Thomas E. , Brooks David J. , Vorup-Jensen Thomas
Published: February 2024

The peripheral immune system is important in neurodegenerative diseases, both in protecting and inflaming the brain, but the underlying mechanisms remain elusive. Alzheimer’s Disease is commonly preceded by a prodromal period. Here, we report the presence of large Aβ aggregates in plasma from patients with mild cognitive impairment (n = 38). The aggregates are associated with low level Alzheimer’s Disease-like brain pathology as observed by 11C-PiB PET and 18F-FTP PET and lowered CD18-rich monocytes. We characterize complement receptor 4 as a strong binder of amyloids and show Aβ aggregates are preferentially phagocytosed and stimulate lysosomal activity through this receptor in stem cell-derived microglia. KIM127 integrin activation in monocytes promotes size selective phagocytosis of Aβ. Hydrodynamic calculations suggest Aβ aggregates associate with vessel walls of the cortical capillaries. In turn, we hypothesize aggregates may provide an adhesion substrate for recruiting CD18-rich monocytes into the cortex. Our results support a role for complement receptor 4 in regulating amyloid homeostasis.
Meiotic recombination dynamics in plants with repeat-based holocentromeres shed light on the primary drivers of crossover patterning
Authors: Castellani Marco , Zhang Meng , Thangavel Gokilavani , Mata-Sucre Yennifer , Lux Thomas , Campoy José A. , Marek Magdalena , Huettel Bruno , Sun Hequan , Mayer Klaus F. X. , Schneeberger Korbinian , Marques André
Published: February 2024

Centromeres strongly affect (epi)genomic architecture and meiotic recombination dynamics, influencing the overall distribution and frequency of crossovers. Here we show how recombination is regulated and distributed in the holocentric plant Rhynchospora breviuscula, a species with diffused centromeres. Combining immunocytochemistry, chromatin analysis and high-throughput single-pollen sequencing, we discovered that crossover frequency is distally biased, in sharp contrast to the diffused distribution of hundreds of centromeric units and (epi)genomic features. Remarkably, we found that crossovers were abolished inside centromeric units but not in their proximity, indicating the absence of a canonical centromere effect. We further propose that telomere-led synapsis of homologues is the feature that best explains the observed recombination landscape. Our results hint at the primary influence of mechanistic features of meiotic pairing and synapsis rather than (epi)genomic features and centromere organization in determining the distally biased crossover distribution in R. breviuscula, whereas centromeres and (epi)genetic properties only affect crossover positioning locally.
Artificial-goosebump-driven microactuation
Authors: Zhang Mingchao , Pal Aniket , Lyu Xianglong , Wu Yingdan , Sitti Metin
Published: February 2024

Microactuators provide controllable driving forces for precise positioning, manipulation and operation at the microscale. Development of microactuators using active materials is often hampered by their fabrication complexity and limited motion at small scales. Here we report light-fuelled artificial goosebumps to actuate passive microstructures, inspired by the natural reaction of hair bristling (piloerection) on biological skin. We use light-responsive liquid crystal elastomers as the responsive artificial skin to move three-dimensionally printed passive polymer microstructures. When exposed to a programmable femtosecond laser, the liquid crystal elastomer skin generates localized artificial goosebumps, resulting in precise actuation of the surrounding microstructures. Such microactuation can tilt micro-mirrors for the controlled manipulation of light reflection and disassemble capillary-force-induced self-assembled microstructures globally and locally. We demonstrate the potential application of the proposed microactuation system for information storage. This methodology provides precise, localized and controllable manipulation of microstructures, opening new possibilities for the development of programmable micromachines.
Bragg glass signatures in PdxErTe3 with X-ray diffraction temperature clustering
Authors: Mallayya Krishnanand , Straquadine Joshua , Krogstad Matthew J. , Bachmann Maja D. , Singh Anisha G. , Osborn Raymond , Rosenkranz Stephan , Fisher Ian R. , Kim Eun-Ah
Published: February 2024

The Bragg glass phase is a nearly perfect crystal with glassy features predicted to occur in vortex lattices and charge-density-wave systems in the presence of disorder. Detecting it has been challenging, despite its sharp theoretical definition in terms of diverging correlation lengths. Here we present bulk probe evidence supporting a Bragg glass phase in the systematically disordered charge-density-wave material of PdxErTe3. We do this by using comprehensive X-ray data and a machine-learning-based analysis tool called X-ray diffraction temperature clustering (X-TEC). We establish a diverging correlation length in samples with moderate intercalation over a wide temperature range. To enable this analysis, we introduced a high-throughput measure of inverse correlation length that we call peak spread. The detection of Bragg glass order and the resulting phase diagram advance our understanding of the complex interplay between disorder and fluctuations. Moreover, the use of our analysis technique to target fluctuations through a high-throughput measure of peak spread can revolutionize the study of fluctuations in scattering experiments.