bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of implant position and of prosthetic characteristics on the occurrence of peri-implantitis: a retrospective study on periapical radiographs
Authors: Corbella Stefano , Morandi Benedetta , Calciolari Elena , Alberti Alice , Francetti Luca , Donos Nikolaos
Published: November 2023

Objective

The present retrospective study aimed to investigate the influence of malposition on the occurrence of peri-implantitis.

Materials and methods

The study included clinical records of systemically healthy patients with single and partial implant-supported rehabilitations and at least 1-year post-loading follow-up. The parameters collected included implant-related factors, patient-related factors, site-related factors, and prosthesis-related factors. The radiographic measurements were taken by using a dedicated software and the diagnosis of peri-implantitis was made based on all the available clinical and radiographic data. Descriptive statistics were provided for all variables. Following an exploratory approach, an implant-level analysis of factors influencing the occurrence of peri-implantitis was done through a multilevel multivariate logistic regression (mixed).

Results

A total of 180 implants belonging to 90 subjects were randomly selected. Malposition showed no statistically significant association with the occurrence of peri-implantitis. According to the multi-level analysis, the parameters that were significantly associated with peri-implantitis included presence / history of periodontitis (OR = 5.945, 95% CI: 1.093 – 32.334, P = 0.039) and presence of an emergence profile angle ≥ 45° (OR = 9.094, 95% CI: 2.017 – 40.995, P = 0.005).

Conclusions

Implant malposition, as defined following Buser’s criteria (2004), did not influence the occurrence of peri-implantitis in the selected cohort. Conversely, history of periodontitis and presence of a prosthetic emergence profile with an angle ≥ 45° were correlated to an increased risk of peri-implantitis.
Tenapanor for peritoneal dialysis patients with hyperphosphatemia: a phase 3 trial
Authors: Nakayama Masaaki , Kobayashi Shuhei , Kusakabe Miho , Ohara Meiko , Nakanishi Kaoru , Akizawa Tadao , Fukagawa Masafumi
Published: November 2023

Background

Tenapanor is a novel selective inhibitor of intestinal sodium/hydrogen exchanger 3 transporter. This is the first trial to assess the efficacy and safety of tenapanor in Japanese patients with hyperphosphatemia who are undergoing peritoneal dialysis.

Methods

This phase 3, open-label, multicenter, single-arm clinical trial targeted patients whose serum phosphorus was within 3.5–7.0 mg/dL with phosphate binders at screening. After phosphate binder washout, tenapanor was orally administered twice-daily, stepwise from 5 to 30 mg/dose for 16 weeks. The primary endpoint, mean change in serum phosphorus level, was evaluated at week 8. The 16-week treatment period was completed with tenapanor alone, and only one phosphate binder type was allowed for combined use after the primary endpoint.

Results

Of the 54 patients enrolled, 34 completed the study. At week 8, the primary endpoint, mean change in serum phosphorus level (last observation carried forward), was − 1.18 mg/dL (95% confidence interval: − 1.54, − 0.81 mg/dL) with tenapanor. From a baseline value of 7.65 mg/dL, serum phosphorus decreased to 6.14 and 5.44 mg/dL at weeks 8 and 16, respectively, and 46.3% and 76.5% of patients achieved serum phosphorus within 3.5–6.0 mg/dL at week 8 and week 16, respectively. The most common adverse event, diarrhea, occurred in 74.1% of patients; the severity of diarrhea was mild or moderate. Thus, the discontinuation percentage due to diarrhea was low at 5.6%.

Conclusions

Administration of tenapanor resulted in a sufficient reduction in serum phosphorus level at week 8 and was considered safe and tolerable.

Trial registration

NCT04766385.
Cutting edge of endoscopic ultrasound-guided fine-needle aspiration for solid pancreatic lesions
Authors: Ishikawa Takuya , Yamao Kentaro , Mizutani Yasuyuki , Iida Tadashi , Kawashima Hiroki
Published: November 2023

This article provides an extensive review of the advancements and future perspectives related to endoscopic ultrasound-guided tissue acquisition (EUS-TA) for the diagnosis of solid pancreatic lesions (SPLs). EUS-TA, including fine-needle aspiration (EUS-FNA) and fine-needle biopsy (EUS-FNB), has revolutionized the collection of specimens from intra-abdominal organs, including the pancreas. Improvements in the design of needles, collection methods, and specimen processing techniques have improved the diagnostic performance. This review highlights the latest findings regarding needle evolution, actuation number, sampling methods, specimen evaluation techniques, application of artificial intelligence (AI) for diagnostic purposes, and use of comprehensive genomic profiling (CGP). It acknowledges the rising use of Franseen and fork-tip needles for EUS-FNB and emphasizes that the optimal number of actuations requires further study. Methods such as the door-knocking and fanning techniques have shown promise for increasing diagnostic performance. Macroscopic on-site evaluation (MOSE) is presented as a practical rapid specimen evaluation method, and the integration of AI is identified as a potentially impactful development. The study also underscores the importance of optimal sampling for CGP, which can enhance the precision of cancer treatment. Ongoing research and technological innovations will further improve the accuracy and efficacy of EUS-TA.
Joint Developmental Trajectories of Conduct Problems and Hyperactivity/Inattention: Antecedent Risk Markers for Group Membership
Authors: Ross Hannah Mercedes Araminta , Girard Lisa-Christine
Published: November 2023

This study investigated joint trajectories of conduct problems and hyperactivity/inattention from age three to nine in a cohort of 7,507 children in Ireland (50.3% males; 84.9% Irish). The parent-reported Strengths and Difficulties Questionnaire was used to collect information on conduct problems (CP) and hyperactivity/inattention (HI). Information regarding risk markers was collected when participants were nine-months-old via parent report and standardised assessments. Using a person-centred approach (i.e., group-based multi trajectory modelling), six trajectories were identified: no CP/low HI, low-stable CP/HI, low-declining CP/stable HI, desisting co-occurring CP/HI, pure-increasing HI, and high chronic co-occurring CP/HI. Specific risk markers for group membership included: male sex; birth complications; perceived difficult temperament; lower primary caregiver age and education level, and higher stress level; prenatal exposure to smoking, and indicators of lower socioeconomic status. Primary caregiver-child bonding and having siblings were protective markers against membership in elevated groups. Results suggest support for both ‘pure’ HI and co-occurring trajectories of CP and HI emerging in toddlerhood. However, no support was found for a ‘pure’ CP trajectory, which may support the suggestion that children on a persistent CP trajectory will have coexisting HI. Intervention efforts may benefit from starting early in life and targeting multiple risk markers in families with fewer resources.
Cold atmospheric plasma: a sustainable approach to inactivating viruses, bacteria, and protozoa with remediation of organic pollutants in river water and wastewater
Authors: Hamza Ibrahim Ahmed , El-Kalliny Amer S. , Abd‑Elmaksoud Sherif , Marouf Mohamed A. , Abdel‑Wahed Mahmoud S. , El-Liethy Mohamed Azab , Hefny Mohamed Mokhtar
Published: November 2023

Innovative technologies are needed to enhance access to clean water and avoid waterborne diseases. We investigated the performance of cold atmospheric plasma (CAP), a clean and sustainable approach for microbial inactivation and total organic carbon (TOC) degradation in environmental water. Water matrices played a crucial role in the performance of CAP efficacy; for example, complete removal of ɸX174 from dH2O required 1 min of treatment, while ɸX174 reductions of ~ 2log10 and 4log10 were obtained after 10 min of CAP exposure in river water and wastewater samples, respectively. Similarly, after 10 min of CAP treatment, bacterial concentrations decreased by 3 log10 and 4 log10, in river and wastewater samples, respectively. In contrast, after 30 s of contact time, a 4 log10 reduction of bacteria was accomplished in dH2O. Complete removal of Acanthamoeba from dH2O was found after 30 min of CAP treatment, whereas it was not removed from surface water or wastewater at the same exposure time. Additionally, the approach successfully reduced TOC, and the degradation kinetics of TOC were represented by pseudo-first-order. CAP showed higher rates of TOC degradation in the final effluent of the wastewater treatment plant compared to surface water. The difference in CAP performance between river water and wastewater could be attributed to the bulk structure of humic acids in river water compared to small organic byproducts in the final effluent of WWTP. Overall, the findings reported here support the idea that CAP holds promise as a sustainable solution for controlling pathogens, removing organic water pollution, and integrating with traditional purification processes. Low-cost systems may advance CAP technology and increase its widespread use.
Gadolinium accumulation and its biochemical effects in Mytilus galloprovincialis under a scenario of global warming
Authors: Andrade Madalena , Soares Amadeu M. V. M. , Solé Montserrat , Pereira Eduarda , Freitas Rosa
Published: November 2023

Electrical and electronic equipment reaching the end of its useful life is currently being disposed of at such an alarmingly high pace that raises environmental concerns. Together with other potentially dangerous compounds, electronic waste contains the rare-earth element gadolinium (Gd), which has already been reported in aquatic systems. Additionally, the vulnerability of aquatic species to this element may also be modified when climate change related factors, like increase in temperature, are taken into consideration. Thus, the present study aimed to evaluate the toxicity of Gd under a scenario of increased temperature in Mytilus galloprovincialis mussels. A multi-biomarker approach and Gd bioaccumulation were assessed in mussels exposed for 28 days to 0 and 10 μg/L of Gd at two temperatures (control – 17 °C; increased – 22 °C). Results confirmed that temperature had a strong influence on the bioaccumulation of Gd. Moreover, mussels exposed to Gd alone reduced their metabolism, possibly to prevent further accumulation, and despite catalase and glutathione S-transferases were activated, cellular damage seen as increased lipid peroxidation was not avoided. Under enhanced temperature, cellular damage in Gd-exposed mussels was even greater, as defense mechanisms were not activated, possibly due to heat stress. In fact, with increased temperature alone, organisms experienced a general metabolic depression, particularly evidenced in defense enzymes, similar to the results obtained under Gd-exposure. Overall, this study underlines the importance of conducting environmental risk assessment taking into consideration anticipated climate change scenarios and exposures to emerging contaminants at relevant environmental concentrations.
Tricky Truths: How Should Alethic Pluralism Accommodate Racial Truths?
Authors: van der Merwe Ragnar , Msimang Phila
Published: November 2023

Some alethic pluralists maintain that there are two kinds of truths operant in our alethic discourse: a realist kind and an anti-realist kind. In this paper, we argue that such a binary conception cannot accommodate certain social truths, specifically truths about race. Most alethic pluralists surprisingly overlook the status of racial truths. Douglas Edwards is, however, an exception. In his version of alethic pluralism—Determination Pluralism—racial truths are superassertible (anti-realist) true rather than correspondence (realist) true. We argue that racial truths exhibit features of both superassertibility (anti-realism) and correspondence (realism). This suggests a fuzzy boundary between realist and anti-realist kinds of truth. There may be a continuum rather than a dichotomy of truths. We conclude by sketching one way for alethic pluralists to accommodate such a notion.
Exploring the emotional and thematic matrix of dreams during war: the role of anxiety and depression
Authors: Kaźmierczak Izabela , Zajenkowska Anna , Bodecka-Zych Marta , Jasielska Dorota , Olechowska Anna , Molińska Weronika , Moniuszko Karolina
Published: November 2023

Dreams serve as a psychological space where the human mind grapples with burdensome issues, and war undoubtedly falls into that category. Inspired by Charlotte Beradt’s work on analyzing dreams during the Third Reich, we collected dreams from a sample of Polish individuals (N = 90) during the outbreak of war in March 2022. Our objective was to identify the most intense emotions conveyed through these dreams and investigate differences in both emotional intensity and dream content between individuals with high levels of anxiety and closely related depression, and those with lower levels of anxiety. We employed a mixed-method study design. The prevailing emotions observed in the dreams were surprise, fear, and sadness. Interestingly, the dreams of participants with higher levels of anxiety exhibited less surprise compared to the comparison group. Additionally, we found that dreams reported by individuals with higher levels of depression conveyed a greater sense of sadness than those in the comparison group. Content analysis revealed that anxious individuals’ dreams prominently featured horror, which evoked feelings of powerlessness rather than surprise. In contrast, the dreams of non-anxious individuals exhibited a dynamic narrative with numerous twists and turns, creating a simultaneous presence and absence of threats. Consequently, the resulting vagueness and uncertainty likely contributed to the element of surprise.
Stability of the Quermassintegral Inequalities in Hyperbolic Space
Authors: Sahjwani Prachi , Scheuer Julian
Published: November 2023

For the quermassintegral inequalities of horospherically convex hypersurfaces in the$$(n+1)$$(n+1)-dimensional hyperbolic space, where$$n\ge 2$$n≥2, we prove a stability estimate relating the Hausdorff distance to a geodesic sphere by the deficit in the quermassintegral inequality. The exponent of the deficit is explicitly given and does not depend on the dimension. The estimate is valid in the class of domains with upper and lower bound on the inradius and an upper bound on a curvature quotient. This is achieved by some new initial value-independent curvature estimates for locally constrained flows of inverse type.
An efficient 3D cell-based discrete fracture-matrix flow model for digitally captured fracture networks
Authors: Sun Lei , Li Mei , Abdelaziz Aly , Tang Xuhai , Liu Quansheng , Grasselli Giovanni
Published: November 2023

Complex hydraulic fracture networks are critical for enhancing permeability in unconventional reservoirs and mining industries. However, accurately simulating the fluid flow in realistic fracture networks (compared to the statistical fracture networks) is still challenging due to the fracture complexity and computational burden. This work proposes a simple yet efficient numerical framework for the flow simulation in fractured porous media obtained by 3D high-resolution images, aiming at both computational accuracy and efficiency. The fractured rock with complex fracture geometries is numerically constructed with a cell-based discrete fracture-matrix model (DFM) having implicit fracture apertures. The flow in the complex fractured porous media (including matrix flow, fracture flow, as well as exchange flow) is simulated with a pipe-based cell-centered finite volume method. The performance of this model is validated against analytical/numerical solutions. Then a lab-scale true triaxial hydraulically fractured shale sample is reconstructed, and the fluid flow in this realistic fracture network is simulated. Results suggest that the proposed method achieves a good balance between computational efficiency and accuracy. The complex fracture networks control the fluid flow process, and the opened natural fractures behave as primary fluid pathways. Heterogeneous and anisotropic features of fluid flow are well captured with the present model.
Molecular characterization of Newcastle disease virus obtained from Mawenzi live bird market in Morogoro, Tanzania in 2020–2021
Authors: Tsaxra John B. , Abolnik Celia , Kelly Terra R. , Chengula Augustino A. , Mushi James R. , Msoffe Peter L. M. , Muhairwa Amandus P. , Phiri Thandeka , Jude Rachel , Chouicha Nadira , Mollel Esther L. , Zhou Huaijun , Gallardo Rodrigo A.
Published: November 2023

Newcastle disease (ND) is among the most important poultry diseases worldwide. It is the major threat to poultry production in Africa and causes major economic losses for both local and commercial chickens. To date, half of ND class II genotypes have been reported in Africa (I, IV, V, VI, VII, XI, XIII, XIV, XVII, XVIII, and XXI). The information on the circulating NDV genotypes is still scarce despite the endemic nature of ND in most countries on the African continent.A total of 659 oro-cloacal swabs were collected from local chickens in Mawenzi live bird market located in Morogoro, Tanzania, between June 2020 and May 2021. Newcastle disease virus was detected by using reverse transcription real-time polymerase chain reaction (RT-qPCR) and conventional PCR followed by sequencing of PCR products. The prevalence of NDV in the surveilled live bird markets was 23.5%. Sequencing and phylogenetic analysis revealed the presence of sub-genotype VII.2. The detected sub-genotype VII.2 has phylogenetic links to Zambian NDV strains implying a Southeast dissemination of the virus, considering that it was first detected in Mozambique. This study underscores the need of active NDV surveillance to determine the distribution of this NDV genotype in the country and monitor its spread and contribution to the emergence of new ND viruses.
Using Bayesian Dynamic Borrowing to Maximize the Use of Existing Data: A Case-Study
Authors: Edwards Dawn , Best N. , Crawford J. , Zi L. , Shelton C. , Fowler A.
Published: November 2023

Bayesian Dynamic Borrowing (BDB) designs are being increasingly used in clinical drug development. These methods offer a mathematically rigorous and robust approach to increase efficiency and strengthen evidence by integrating existing trial data into a new clinical trial. The regulatory acceptability of BDB is evolving and varies between and within regulatory agencies. This paper describes how BDB can be used to design a new randomised clinical trial including external data to supplement the planned sample size and discusses key considerations related to data re-use and BDB in drug development programs. A case-study illustrating the planning and evaluation of a BDB approach to support registration of a new medicine with the Center for Drug Evaluation in China will be presented. Key steps and considerations for the use of BDB will be discussed and evaluated, including how to decide whether it is appropriate to borrow external data, which external data can be re-used, the weight to put on the external data and how to decide if the new study has successfully demonstrated treatment benefit.
War and Peace: Orthodox Icons and Putin's Politics of the Sacred
Authors: Adams Amy Singleton
Published: November 2023

This study examines twenty years of data about Vladimir Putin's ritualized encounters with icons as a form of symbolic political discourse on the “sacred” that ultimately devolved into Russia's violent escalation of the Russo-Ukraine War in February 2022. Theories of semiotics, the sacred, and studies on iconography reveal patterns of carefully curated engagement with the sacred images that draw on historical relationships among religiosity, power, and violence in Russia. The analysis shows how semiotic signalling through iconographical forms allow Putin to sacralize and strengthen his leadership within the sphere of domestic politics. It demonstrates how Putin's interaction with icons during annual visits to regional Christmas services re-sacralized Russian territory and reinforced national security priorities to a domestic audience. Turning to the international stage, this essay shows how Putin's “icon diplomacy” establishes “sacred” space beyond Russia's national borders. The metaphor of the iconographical image is realized in Ukraine, as both sides struggle to control the narrative of the sacred. The study demonstrates the relationship between violence and the sacred as it pertains to Putin's political lexicon and the importance of understanding this relationship in order to fathom his language of icons.
Seismic Imaging of the Westward Transition From Yakutat to Pacific Subduction in Southern Alaska
Authors: Millet Florian , Rondenay Stéphane , Bodin Thomas , Tape Carl
Published: November 2023

Alaska is located at the northernmost point of the interface between the Pacific plate and the North American continent. The subduction of the Pacific plate generates arc volcanoes along the Aleutian trench, which stops to the east at the Denali Volcanic Gap. This volcanic gap has been linked to the underthrusting of the Yakutat terrane, which might alter the thermal state of the mantle wedge and prevent melt formation. This implies that the limits of the volcanic activity should mirror the extent of the Yakutat subduction. However, the transition from the Pacific slab to the Yakutat terrane at depth is not fully understood. To investigate this issue, we processed a new composite seismic data set from six arrays deployed in the region from 2000 to 2018. We apply a multi‐mode 3D Kirchhoff migration to obtain high‐resolution 3D scattering images of the region. Our results highlight a sharp lateral boundary in the slab structure, with a 10 km Moho step, just offshore Anchorage, and a more gradual slab transition beneath the southern part of the Kenai peninsula. Our images from the Yakutat slab plunge down to 150 km depth are consistent with previous estimates of the Yakutat slab extent below the Alaska Range. Although the steeply dipping boundaries of the subducting Pacific lithospheres are not fully recovered, deep coherent signals from the Pacific slab are observed down to 150 km depth. These observations suggest that the crust is still partially uneclogitized at these depths in both slabs.
SMatStack to Enhance Noisy Teleseismic Seismic Phases: Validation and Application to Resolving Depths of Oceanic Transform Earthquakes
Authors: Fang Hongjian , Abercrombie Rachel E.
Published: November 2023

The depths of most moderate‐sized oceanic earthquakes are poorly constrained because of the lack of local recording stations and noisy teleseismic recordings. This hampers our understanding of slip behaviors along oceanic faults and the mechanical properties of the oceanic lithosphere. In this study, we develop a new method to enhance the weak body‐wave signals, particularly the depth phases, associated with earthquakes on oceanic transform faults using large‐aperture arrays in the teleseismic range. We simulate the enhanced teleseismic signals to refine the centroid depths of moderate‐sized earthquakes. We validate the new approach using synthetic waveforms and show it outperforms conventional methods when dealing with noisy signals. We obtain the depth estimates for three moderate‐sized earthquakes on the Chain transform fault in the equatorial Atlantic Ocean and find two of them are consistent with a local catalog derived using oceanic bottom seismometers. Application of the new method to the past decades of teleseismic recordings of moderate‐sized earthquakes on the large and slow‐slipping transform faults will provide significantly improved constraints on the width of the seismogenic zone, thus advancing our understanding of the rheology of oceanic lithosphere and earthquake processes in oceanic settings and, by comparison, their more dangerous continental counterparts. The new method is not limited to oceanic transform earthquakes, but can be easily adapted to other seismological studies in which noisy but coherent signals could be revisited for better usage.
Electron Backflow Motions in the Outer Electron Diffusion Region During Magnetic Reconnection
Authors: Xiong Q. Y. , Huang S. Y. , Yuan Z. G. , Jiang K. , Xu S. B. , Lin R. T. , Yu L.
Published: November 2023

Magnetic reconnection is a fundamental physical process of rapidly converting magnetic energy into particles. The electron diffusion region (EDR) is the crucial region during magnetic reconnection. The outer EDR, which also plays a crucial role in magnetic reconnection, is responsible for energy conversion. In the outer EDR, the electrons are decelerated and return the energy to the magnetic field on the pileup region behind the reconnection front. In the present study, we used the fully kinetic particle‐in‐cell simulation and revealed that part of decelerated electrons in the outer EDR could even move back to the inner EDR. This phenomenon is caused by the dominant contribution from the magnetic tension force, and it suggests a magnetic Marangoni effect in space plasma, similar to the Marangoni effect in fluids. Our results potentially propose a brand‐new physical process and a novel mechanism in the EDR during magnetic reconnection.
Zonal Structure of Tropical Pacific Surface Salinity Anomalies Affects the Eastern and Central Pacific El Niños Differently
Authors: Guan Cong , Tian Feng , McPhaden Michael J. , Hu Shijian , Wang Fan
Published: November 2023

Maximum sea surface salinity (SSS) anomalies are found in the central Pacific during the eastern Pacific El Niño (EPEN) and located further westward during the central Pacific El Niño (CPEN), but whether these differences affect event strengths is unclear. By performing ocean general circulation model experiments via modifying freshwater flux anomalies, we find salinity effects on surface warming during both types are highly sensitive to zonal locations of SSS anomalies, with the strongest warming induced by the SSS anomalies near the international dateline. Further analysis reveals that vertical mixing and entrainment dominate this temperature sensitivity, with the strongest response to SSS anomalies occurring in the central Pacific. The central‐Pacific SSS anomalies increase EPEN warming by 0.15°C while the westward‐located SSS anomalies make little contribution to CPEN warming. Therefore, the distinct zonal structures of SSS anomalies facilitate stronger EPEN than the CPEN, increasing their difference in intensity by about 10%.
Temperature Thresholds for Carbon Flux Variation and Warming‐Induced Changes
Authors: Fu Congsheng , Wang Guiling , Yang Yuting , Wu Huawu , Wu Haohao , Zhang Haixia , Xia Ye
Published: November 2023

The response of net ecosystem exchange (NEE) to environmental changes is strongly nonlinear, characterized with threshold behaviors that are not well understood. Here, we investigated the threshold behaviors in the relationship between NEE and surface air temperature based on FLUXNET2015 observations, Community Land Model simulations, and Coupled Model Intercomparison Project Phase 6 (CMIP6) model outputs. An air temperature threshold of 16.4°C, corresponding to the maximum carbon sink (Tsink), was identified for all 205 FLUXNET2015 sites combined. For deciduous broadleaf and mixed forests, wetlands and wheat‐barley croplands, and rice‐maize‐soybean croplands, we identified a carbon‐source threshold (Tsource) of 6.8, 5.0, and 18.0°C, respectively, beyond which the ecosystem becomes less of a carbon source. Five cold climate types mainly encompassing these plant functional types showed a clear carbon‐source Tsource of 12.2°C. Six CMIP6 models project a threshold temperature increase of 1.0–2.8°C by the 2090s, which results primarily from a shift of the optimum temperature for gross primary production. Not accounting for the warming‐induced threshold changes may lead to an estimated time of the average summer air temperature passing Tsink that is earlier by 4.5–6.7 and 6.4–12.2 years at low (15°N–15°S) and high (≥60°S or ≥ 60°N) latitudes, respectively.
The long-term health outcomes, pathophysiological mechanisms and multidisciplinary management of long COVID
Authors: Li Jingwei , Zhou Yun , Ma Jiechao , Zhang Qin , Shao Jun , Liang Shufan , Yu Yizhou , Li Weimin , Wang Chengdi
Published: November 2023

There have been hundreds of millions of cases of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With the growing population of recovered patients, it is crucial to understand the long-term consequences of the disease and management strategies. Although COVID-19 was initially considered an acute respiratory illness, recent evidence suggests that manifestations including but not limited to those of the cardiovascular, respiratory, neuropsychiatric, gastrointestinal, reproductive, and musculoskeletal systems may persist long after the acute phase. These persistent manifestations, also referred to as long COVID, could impact all patients with COVID-19 across the full spectrum of illness severity. Herein, we comprehensively review the current literature on long COVID, highlighting its epidemiological understanding, the impact of vaccinations, organ-specific sequelae, pathophysiological mechanisms, and multidisciplinary management strategies. In addition, the impact of psychological and psychosomatic factors is also underscored. Despite these crucial findings on long COVID, the current diagnostic and therapeutic strategies based on previous experience and pilot studies remain inadequate, and well-designed clinical trials should be prioritized to validate existing hypotheses. Thus, we propose the primary challenges concerning biological knowledge gaps and efficient remedies as well as discuss the corresponding recommendations.
Coordinated proteome change precedes cell lysis and death in a mat-forming cyanobacterium
Authors: Zorz Jackie , Paquette Alexandre J , Gillis Timber , Kouris Angela , Khot Varada , Demirkaya Cigdem , De La Hoz Siegler Hector , Strous Marc , Vadlamani Agasteswar
Published: November 2023

Cyanobacteria form dense multicellular communities that experience transient conditions in terms of access to light and oxygen. These systems are productive but also undergo substantial biomass turnover through cell death, supplementing heightened heterotrophic respiration. Here we use metagenomics and metaproteomics to survey the molecular response of a mat-forming cyanobacterium undergoing mass cell lysis after exposure to dark and anoxic conditions. A lack of evidence for viral, bacterial, or eukaryotic antagonism contradicts commonly held beliefs on the causative agent for cyanobacterial death during dense growth. Instead, proteogenomics data indicated that lysis likely resulted from a genetically programmed response triggered by a failure to maintain osmotic pressure in the wake of severe energy limitation. Cyanobacterial DNA was rapidly degraded, yet cyanobacterial proteins remained abundant. A subset of proteins, including enzymes involved in amino acid metabolism, peptidases, toxin-antitoxin systems, and a potentially self-targeting CRISPR-Cas system, were upregulated upon lysis, indicating possible involvement in the programmed cell death response. We propose this natural form of cell death could provide new pathways for controlling harmful algal blooms and for sustainable bioproduct production.
Narrative medicine pinpoints loss of autonomy and stigma in Parkinson’s disease
Authors: Florijn Barend W. , Kloppenborg Raoul , Kaptein Ad A. , Bloem Bastiaan R.
Published: November 2023

Parkinson’s disease characteristics can create a self-perceived sense of stigmatization and disapproval by others, thereby affecting self-perceived autonomy. This study investigated the metaphors related to the loss of autonomy and stigma in stories and drawings of Parkinson’s disease. We compare a contemporary first-person illness narrative and -drawing from a person with Parkinson’s disease, with two novels (Jonathan Franzen’sThe Correctionsand Claudia Piñeiro’s Elena Knows), a graphic novel(Peter Dunlap-Shohl’sMy Degeneration: A Journey Through Parkinson’s), a non-fiction book (Oliver Sacks’Awakenings) and a first-person illness narrative (John Palfreman’sThe Bright Side of Parkinson’s). Metaphors in the patient narrative, novels, and non-fiction work were reviewed and a list of themes or categorizations common to 2 of the metaphors was generated. Parkinson’s disease metaphors indicate a ‘Parkinson’s prism’ thereby depicting extreme experiences (24.4%) like a ‘fall by mischance’, a ‘tantrum of selfish misery’ or a ‘bottomless darkness and unreality’ (Table 1). Both novels signify a sense of ‘betrayal and disconnection’ in the Parkinson’s disease experience while non-fiction of Parkinsonism depicts aspacein which one feels ‘caged and deprived’. This makes the Parkinson’s disease narrative a chaos story that could influence the decision to initiate treatment and treatment adherence. We conclude that narrative medicine can help to focus the medical consultations with affected individuals on issues that matter most to them, thereby improving self-perceived autonomy and stigma. As such, it is a critical component of the much-needed move towards personalized medicine in Parkinson’s disease, achieved through the reciprocity of thinking with stories.
The effect of immunomodulatory drugs on aortic stenosis: a Mendelian randomisation analysis
Authors: Ciofani Jonathan L. , Han Daniel , Nazarzadeh Milad , Allahwala Usaid K. , De Maria Giovanni Luigi , Banning Adrian P. , Bhindi Ravinay , Rahimi Kazem
Published: November 2023

There are currently no approved pharmacological treatment options for aortic stenosis (AS), and there are limited identified drug targets for this chronic condition. It remains unclear whether inflammation plays a role in AS pathogenesis and whether immunomodulation could become a therapeutic target. We evaluated the potentially causal association between inflammation and AS by investigating the genetically proxied effects of tocilizumab (IL6 receptor, IL6R, inhibitor), canakinumab (IL1β inhibitor) and colchicine (β-tubulin inhibitor) through a Mendelian randomisation (MR) approach. Genetic proxies for these drugs were identified as single nucleotide polymorphisms (SNPs) in the gene, enhancer or promoter regions of IL6R, IL1β or β-tubulin gene isoforms, respectively, that were significantly associated with serum C-reactive protein (CRP) in a large European genome-wide association study (GWAS; 575,531 participants). These were paired with summary statistics from a large GWAS of AS in European patients (653,867 participants) to then perform primary inverse-variance weighted random effect and sensitivity MR analyses for each exposure. This analysis showed that genetically proxied tocilizumab was associated with reduced risk of AS (OR 0.56, 95% CI 0.45–0.70 per unit decrease in genetically predicted log-transformed CRP). Genetically proxied canakinumab was not associated with risk of AS (OR 0.80, 95% CI 0.51–1.26), and only one suitable SNP was identified to proxy the effect of colchicine (OR 34.37, 95% CI 1.99–592.89). The finding that genetically proxied tocilizumab was associated with reduced risk of AS is concordant with an inflammatory hypothesis of AS pathogenesis. Inhibition of IL6R may be a promising therapeutic target for AS management.
Effects of climatic and environmental factors on mosquito population inferred from West Nile virus surveillance in Greece
Authors: Ferraccioli Federico , Riccetti Nicola , Fasano Augusto , Mourelatos Spiros , Kioutsioukis Ioannis , Stilianakis Nikolaos I.
Published: November 2023

Mosquito-borne diseases’ impact on human health is among the most prominent of all communicable diseases. With limited pool of tools to contrast these diseases, public health focus remains preventing mosquito-human contacts. Applying a hierarchical spatio-temporal Bayesian model on West Nile virus (WNV) surveillance data from Greece, we aimed to investigate the impact of climatic and environmental factors on Culex mosquitoes’ population. Our spatio-temporal analysis confirmed climatic factors as major drivers of WNV-transmitting-Culex mosquitoes population dynamics, with temperature and long periods of moderate-to-warm climate having the strongest positive effect on mosquito abundance. Conversely, rainfall, high humidity, and wind showed a negative impact. The results suggest the presence of statistically significant differences in the effect of regional and seasonal characteristics, highlighting the complex interplay between climatic, geographical and environmental factors in the dynamics of mosquito populations. This study may represent a relevant tool to inform public health policymakers in planning preventive measures.
Causal effects of genetically determined blood metabolites on multiple myeloma: a Mendelian randomization study
Authors: Ren Jialin , Wu Min
Published: November 2023

Previous studies have shown that metabolites play an important role in phenotypic regulation. However, the causal relationship between metabolites and multiple myeloma has not been adequately investigated. Here, we attempt to explore the causal effects of genetically determined blood metabolites on multiple myeloma. The large-scale public blood metabolites and multiple myeloma datasets from independently published genome-wide association studies (GWAS) were used to explore the causal relationship between each genetically determined blood metabolite and multiple myeloma through inverse variance weighted (IVW), weighted median, MR-Egger and mode-based estimation methods. Sensitivity tests were performed to evaluate the stability and reliability of the results by MR-Egger regression and leave-one-out methods. Metabolic pathway analysis was further explored using filtered data. Statistical analyses were all performed in R. Among 452 metabolites, ten known metabolites and three unknown metabolites had significant causal relationship with multiple myeloma (P < 0.05). Four known metabolites, 3-methyl-2-oxovalenate, oxidized bilirubin, isovalerylcarnitine and glutamine carnitine, reached statistical significance in IVW models. Metabolic pathways analysis identified four significant pathways. The occurrence of multiple myeloma may have a causal relationship with these four metabolites, and there are four metabolic pathways that are also related to the occurrence of multiple myeloma. This can provide new ideas for exploring early screening and treatment of multiple myeloma.
Single-cell RNA sequencing revealed potential targets for immunotherapy studies in hepatocellular carcinoma
Authors: Xie Zhouhua , Huang Jinping , Li Yanjun , Zhu Qingdong , Huang Xianzhen , Chen Jieling , Wei Cailing , Luo Shunda , Yang Shixiong , Gao Jiamin
Published: November 2023

Hepatocellular carcinoma (HCC) is a solid tumor prone to chemotherapy resistance, and combined immunotherapy is expected to bring a breakthrough in HCC treatment. However, the tumor and tumor microenvironment (TME) of HCC is highly complex and heterogeneous, and there are still many unknowns regarding tumor cell stemness and metabolic reprogramming in HCC. In this study, we combined single-cell RNA sequencing data from 27 HCC tumor tissues and 4 adjacent non-tumor tissues, and bulk RNA sequencing data from 374 of the Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) samples to construct a global single-cell landscape atlas of HCC. We analyzed the enrichment of signaling pathways of different cells in HCC, and identified the developmental trajectories of cell subpopulations in the TME using pseudotime analysis. Subsequently, we performed transcription factors regulating different subpopulations and gene regulatory network analysis, respectively. In addition, we estimated the stemness index of tumor cells and analyzed the intercellular communication between tumors and key TME cell clusters. We identified novel HCC cell clusters that specifically express HP (HCC_HP), which may lead to higher tumor differentiation and tumor heterogeneity. In addition, we found that the HP gene expression-positive neutrophil cluster (Neu_AIF1) had extensive and strong intercellular communication with HCC cells, tumor endothelial cells (TEC) and cancer-associated fibroblasts (CAF), suggesting that clearance of this new cluster may inhibit HCC progression. Furthermore, ErbB signaling pathway and GnRH signaling pathway were found to be upregulated in almost all HCC tumor-associated stromal cells and immune cells, except NKT cells. Moreover, the high intercellular communication between HCC and HSPA1-positive TME cells suggests that the immune microenvironment may be reprogrammed. In summary, our present study depicted the single-cell landscape heterogeneity of human HCC, identified new cell clusters in tumor cells and neutrophils with potential implications for immunotherapy research, discovered complex intercellular communication between tumor cells and TME cells.
Bibliometric Analysis: Analysis of Government Social Media Innovations from 2012 to 2023
Authors: Iqbal Kholidin Muhammad
Published: November 2023

Government social media innovation is a trend carried out as an effort to respond to needs in the era of technological development and as an effort to improve services, especially in the public sector. Therefore, government social media innovation has become one of the research topics developed in recent years. As research on the topic of government social media innovation continues to develop, stakeholders need an up-to-date perspective on government social media innovation research. The aim of this research is to provide an objective and accurate summary of government social media innovation research using 194 documents taken from the Scopus database and analyzed using a bibliometric approach. Research was analyzed by publication per year, country of contributor, subject area, author, affiliation, and source. This research uses the CiteSpace application to analyze connectivity trends on related topics using keywords and reference nodes. The results of this research are useful for identifying clusters and research in communities such as royal colleges, sustainable development, public service delivery, and other clusters. This research can contribute to the body of knowledge quantitatively and accurately in terms of contributing to the knowledge map regarding government social media innovation and can be used as material for research reviews on similar topics and developed in the future.
Complete C4-C5 Dislocation Secondary to Shallow Water Diving in a Child: A Case-Based Update
Authors: Matos Luís Eduardo Oliveira , Figueiredo Gabriel Sá , Monteiro Matheus Brasil Câmara , Esmeraldo Mateus Aragão , Ponte Keven Ferreira da , Cristino-Filho Gerardo , Leal Paulo Roberto Lacerda
Published: November 2023

Introduction Pediatric spinal cord injury (PSCI) is rare, especially secondary to shallow water diving, with only a few cases recorded in the literature. Due to the low standardization in the diagnosis and treatment of this condition, each of these cases requires a personalized approach.

Case Description A 10-year-old female patient presented with tetraparesis and C5 sensory level secondary to spinal trauma due to shallow water diving. Computed tomography (CT) revealed complete C4-C5 dislocation, which led to a neurosurgical approach preceded by an intraoperative manual maneuver to reduce the dislocation. Following complete surgical reduction of the dislocation, the patient presented immediate significant neurological improvement.

Conclusion Children need to be warned about diving, as SCI due to shallow water diving has a poor neurological outcome. Despite that, early diagnosis, stabilization, and surgical approach can lead to immediate significant neurological improvement. Considering the peculiarities of pediatric patients and the existence of varying care techniques in the literature, more studies comparing surgical and nonsurgical outcomes are fundamental.
Assessment of the Benefit of Intraoperative Cortical Stimulation in Patients with Lesions within Eloquent Brain Regions
Authors: Garcia Luiz Alberto Otoni , Giannetti Alexandre Varella
Published: November 2023

Objective The present study sought to evaluate the benefits of intraoperative cortical stimulation (CS) for reducing morbidity in neurosurgery.

Method A total of 56 patients were submitted to neurosurgical procedure with the aid of CS. Initially, surgical exposure and planned resection were based on anatomy and imaging exams, which were followed by CS. According to the findings, the patients were divided into two groups. In group 1 the previous surgical strategy had to be altered, while in group 2 the surgical planning did not suffer any interference. Patients were also divided into subgroups according to the underlying disease: gliomas or other etiologies. Transient and definitive deficits occurrence were compared between groups 1 and 2 and subgroups of etiologies. The real benefit of CS technique was calculated by a specific formula.

Results There were 20 patients (37.5%) whose surgical strategy was changed based on CS findings. Furthermore, 65% of group 1 patients had transient deficit, in comparison to 30.5% of patients in group 2 (p = 0.013). As for the definitive deficit, it occurred in 15.0% of group 1 patients versus 8.3% of patients in group 2 (p = 0.643). Definitive deficits with no statistical difference (p = 0.074) were found in 17.2% of patients with gliomas, while none were found in the other etiologies subgroup. The rate of real benefit of intraoperative CS was 30.4%. Considering the subgroups of gliomas and other etiologies, the benefit rates were 25.7% and 38.1%, respectively.

Conclusions The surgical decision was influenced by CS in 35.7% of the cases and prevented definitive deficit in 30% of patients.
Racing Performance and Sale Result in 145 Thoroughbreds after Arthroscopic Removal of Osteochondral Fragments from the Lateral Femoral Trochlear Ridge as a Yearling (2012–2015)
Authors: Kerbert Maria P. , Freeland Russell B. , Verhaar Nicole , Baker William T.
Published: November 2023

Objectives The lateral trochlear ridge (LTR) of the femur is the most common predilection site for osteochondritis dissecans (OCD) in the equine stifle. The objective was to investigate the relationship between lesion size, racing performance, and sale result of Thoroughbreds with LTR OCD following arthroscopic removal as a yearling.

Methods In this retrospective study, medical records of 145 Thoroughbreds from one equine hospital that underwent surgery for LTR OCD were reviewed; the length and depth of the lesions were measured on preoperative radiographs. Horses were allocated to group S if they were presented to a public yearling sale post-surgery, and horses in group NS were not. Each horse from group S was matched with two control horses from the same sale (group C). Influence of lesion size on racing performance and sale result was analyzed. Racing performance and sale results were compared between different categories of OCD lesion sizes and between the groups.

Results Lesion length and depth did not affect racing performance and did not differ between group S and group NS. However, group S did perform significantly better than group NS. When comparing groups S and C, there were no significant differences in racing performance and sale result.

Conclusion Thoroughbreds that had arthroscopic surgery for LTR OCD as a yearling and were presented on a public yearling sale performed comparable to Thoroughbreds that showed similar potential as a yearling. Sale result is not significantly affected in our study.