bluuebunny/crossref_metadata_2025 huggingface dataset:
Anaesthesia and cancer recurrence: the influence of perioperative anaesthetic technique on cancer recurrence after surgery
Authors: Rahmani Lua S. , Abdelaatti Ahmed , Wall Thomas P. , Buggy Donal J.
Published: March 2023

Purpose of review

Cancer is a leading cause of death worldwide, and incidence is increasing. Excisional surgery is essential in approximately 70% of solid organ tumours. Emerging research in onco-anaesthesiology suggests that perioperative anaesthetic and analgesic techniques might influence long-term oncologic outcomes.

Recent findings

Prospective, randomized control trials (RCTs) demonstrate that perioperative regional and neuraxial anaesthetic techniques do not affect cancer recurrence. Ongoing trials are investigating the potential outcome benefits of systemic lidocaine. Retrospective studies indicate improved postoperative oncologic outcomes for certain types of breast cancer with higher intraoperative opioid dosage, nuancing available evidence on the effect of opioids. RCT evidence suggests that propofol has no beneficial effect compared with volatiles on breast cancer recurrence, although it remains unclear whether this applies to other cancer types.

Although regional anaesthesia definitively does not affect cancer recurrence, ongoing prospective RCTs with oncological outcomes as primary endpoints are awaited to establish if other anaesthetic or analgesic techniques influence cancer recurrence. Until such trials conclusively identify a causal relationship, insufficient evidence exists to recommend specific anaesthetic or analgesic techniques for tumour resection surgery based on altering the patient's risk of recurrence.
Absorbance Measurements From Normal-hearing Ears in the National Health and Nutrition Examination Survey, 2015–2016 and 2017–2020
Authors: Sun Jiayi , Horton Nicholas J. , Voss Susan E.
Published: March 2023

Objective:

To summarize absorbance and impedance angles from normal-hearing ears within the 2015–2016 and 2017–2020 US National Health and Nutrition Examination Surveys (NHANES).

Design:

Two publicly available NHANES datasets were analyzed. Ears meeting criteria for normal hearing and valid absorbance and impedance angle measurements were identified. Measurements were summarized via descriptive statistics within categories of age cohort, race/ethnicity cohort, sex (male, female), and ear (left, right).

Results:

A total of 7029 ears from 4150 subjects, ages 6 to 80 years, met inclusion criteria. Differences between subgroups within all categories (age, race/ethnicity, sex, and ear) were fractions of the sample SDs. The largest differences occurred between age cohorts younger than 20 years.

Conclusions:

The NHANES absorbance and impedance angle measurements are consistent with published literature. These results demonstrate that trained professionals, using the Titan instrument in a community setting inclusive of all demographics, produce comparable measurements to those in laboratory settings.
Applying TEC-VARIETY to Motivate and Engage Learners for Online Learning Success
Authors: Chen Weichao , Bonk Curtis J. , Sandars John
Published: March 2023

Learner motivation plays an essential role in overcoming barriers to achieve online learning success. Many health professions educators, however, are not familiar with evidence-based motivational principles and techniques that tap into learners' inner resources to promote online learning success. The TEC-VARIETY (T-Tone; E-Encouragement; C-Curiosity; V-Variety; A-Autonomy; R-Relevance; I-Interactivity; E-Engagement; T-Tension; and Y-Yielding products) framework provides evidence-based principles and techniques that motivate and engage learners. Health professions educators can identify and assemble appropriate activities to motivate and engage online learners. Educators are encouraged to use Design-Based Research to guide their adoption of TEC-VARIETY and evaluation of outcomes.
Clostridium difficile infection and immune checkpoint inhibitor–induced colitis in melanoma: 18 cases and a review of the literature
Authors: Vuillamy Chloé , Arnault Jean-Philippe , Fumery Mathurin , Mortier Laurent , Monestier Sandrine , Mansard Sandrine , Bens Guido , Duval-Modeste Anne-Bénédicte , Funck-Brentano Elisa , Jeudy Géraldine , Machet Laurent , Chaby Guillaume , Dadban Ali , Lok Catherine ,   Groupe de Cancérologie Cutanée de la Société Française de Dermatologie
Published: March 2023

Immunotherapy has become the standard of care for several types of cancer, such as melanoma. However, it can induce toxicity, including immune checkpoint inhibitor–induced colitis (CIC). CIC shares several clinical, histological, biological, and therapeutic features with inflammatory bowel disease (IBD). Clostridium difficile infection (CDI) can complicate the evolution of IBD. We aimed to characterize the association between CDI and CIC in patients treated with anti-CTLA-4 and anti-PD-1 for melanoma. Patients from nine centers treated with anti-CTLA-4 and anti-PD-1 for melanoma and presenting with CDI from 2010 to 2021 were included in this retrospective cohort. The primary endpoint was the occurrence of CIC. The secondary endpoints were findings allowing us to characterize CDI. Eighteen patients were included. Eleven were treated with anti-PD-1, four with anti-CTLA-4, and three with anti-PD-1 in combination with anti-CTLA-4. Among the 18 patients, six had isolated CDI and 12 had CIC and CDI. Among these 12 patients, eight had CIC complicated by CDI, three had concurrent CIC and CDI, and one had CDI followed by CIC. CDI was fulminant in three patients. Endoscopic and histological features did not specifically differentiate CDI from CIC. Nine of 11 patients required immunosuppressive therapy when CDI was associated with CIC. In nine cases, immunotherapy was discontinued due to digestive toxicity. CDI can be isolated or can complicate or reveal CIC. CDI in patients treated with immunotherapy shares many characteristics with CDI complicating IBD. Stool tests for Clostridium difficile should be carried out for all patients with diarrhea who are being treated with immunotherapy.
Increasing national trend of direct-acting antiviral discontinuation among people treated for HCV 2016–2021
Authors: Carson Joanne , Barbieri Sebastiano , Matthews Gail V. , Dore Gregory J. , Hajarizadeh Behzad
Published: March 2023

Background:

Direct-acting antiviral (DAA) treatment discontinuation may negatively impact HCV elimination efforts. In Australia, DAA therapy is pharmacy dispensed, generally in 4-week amounts, with the approved duration (8–24 wk) and volume dispensed reported in pharmaceutical administrative data. This analysis assessed national HCV treatment discontinuation.

Methods:

Individuals commencing DAAs between 2016 and 2021 were assessed for treatment discontinuation. Individuals with a single dispensation of their entire treatment course were excluded. Treatment discontinuation was defined as ≥4 weeks of approved treatment duration not dispensed. Factors associated with treatment discontinuation were assessed using Cox regression. Factors associated with retreatment following treatment discontinuation were assessed using logistic regression.

Results:

Of 95,275 individuals who were treated, 88,986 were included in the analysis of whom 7532 (9%) discontinued treatment. Treatment discontinuation increased from 6% in the first half of 2016 to 15% in 2021. Longer treatment durations (vs. 8 wk) were associated with increased discontinuation risk (12 wk: adjusted HR = 3.23; 95% CI: 2.90, 3.59; p < 0.001, 16–24 wk: adjusted HR = 6.29; 95% CI: 5.55, 7.14; p < 0.001). Of individuals discontinuing treatment, 24% were retreated. Early discontinuation (4 wk treatment dispensed) increased the likelihood of retreatment (adjusted OR = 3.91; 95% CI: 3.44, 4.44; p < 0.001). Those with early discontinuation of glecaprevir/pibrentasvir 8 weeks (vs. sofosbuvir/velpatasvir 12 wk) had a lower likelihood of retreatment (adjusted OR = 0.62; 95% CI: 0.49, 0.79; p < 0.001). Initial treatment discontinuation was associated with an increased risk of retreatment discontinuation (adjusted HR = 4.41; 3.85, 5.05; p < 0.001).

Conclusions:

DAA treatment discontinuation increased over time corresponding to increasing treatment uptake through primary care among people who inject drugs. The use of simplified, short-duration therapies may reduce treatment discontinuation. Access to adherence support and retreatment will be essential for HCV elimination.
Acute rejection after liver transplantation with machine perfusion versus static cold storage: A systematic review and meta-analysis
Authors: Maspero Marianna , Ali Khaled , Cazzaniga Beatrice , Yilmaz Sumeyye , Raj Roma , Liu Qiang , Quintini Cristiano , Miller Charles , Hashimoto Koji , Fairchild Robert L. , Schlegel Andrea
Published: March 2023

Background and Aims:

Acute cellular rejection (ACR) is a frequent complication after liver transplantation. By reducing ischemia and graft damage, dynamic preservation techniques may diminish ACR. We performed a systematic review to assess the effect of currently tested organ perfusion (OP) approaches versus static cold storage (SCS) on post-transplant ACR-rates.

Approach and Results:

A systematic search of Medline, Embase, Cochrane Library, and Web of Science was conducted. Studies reporting ACR-rates between OP and SCS and comprising at least 10 liver transplants performed with either hypothermic oxygenated perfusion (HOPE), normothermic machine perfusion, or normothermic regional perfusion were included. Studies with mixed perfusion approaches were excluded. Eight studies were identified (226 patients in OP and 330 in SCS). Six studies were on HOPE, one on normothermic machine perfusion, and one on normothermic regional perfusion. At meta-analysis, OP was associated with a reduction in ACR compared with SCS [OR: 0.55 (95% CI, 0.33–0.91), p=0.02]. This effect remained significant when considering HOPE alone [OR: 0.54 (95% CI, 0.29–1), p=0.05], in a subgroup analysis of studies including only grafts from donation after cardiac death [OR: 0.43 (0.20–0.91) p=0.03], and in HOPE studies with only donation after cardiac death grafts [OR: 0.37 (0.14–1), p=0.05].

Conclusions:

Dynamic OP techniques are associated with a reduction in ACR after liver transplantation compared with SCS. PROSPERO registration: CRD42022348356.
THE WAY PATIENTS SEE FLOATERS
Authors: Ngo Wei Kiong , Keshet Yariv , Salcedo-Ledesma Alfredo , Walia Jay , Ledesma-Gil Gerardo , Spaide Richard F.
Published: March 2023

Purpose:

To investigate the use of dynamic widefield scanning laser ophthalmoscopy (SLO) and B-scan ultrasonography in imaging vitreous abnormalities in patients with complaints of floaters.

Methods:

Twenty-one patients underwent both dynamic SLO and B-scan ultrasonography to image their vitreous abnormalities. After reviewing these videos, patients graded each imaging technique on a scale of 1 to 10, based on how closely it represented their visual perception of floaters.

Results:

The mean age of the patients (12 women and nine men) was 47.7 ± 18.5 years. The patients graded a median score of nine for SLO imaging (mean = 8.43) compared with a median score of 5 (mean = 4.95) for ultrasound (P = 0.001). Widefield SLO imaging demonstrated three-dimensional interconnectivity within the condensations of the formed vitreous that exhibited translational and rotational movements with eye saccades.

Conclusion:

Floaters are a common complaint, but it is difficult to know whether imaging findings of the vitreous correlate to what patients perceive. Widefield SLO seems to image vitreous abnormalities related to how patients perceive their own floaters better than B-scan ultrasonography. Despite the term “floaters”, the vitreous abnormalities in the videos seemed to be manifestations of a complex three-dimensional degeneration of the vitreous framework.
Association of ocular perfusion pressure and cerebrospinal fluid pressure with changes in diabetic retinopathy
Authors: Lin Zhong , Li Dong , Wen Liang , Wang Yu , Wang Feng Hua , Liang Yuan Bo
Published: March 2023

Purpose:

To investigate the association between mean ocular perfusion pressure (MOPP), estimated cerebrospinal fluid pressure (CSFP), and changes in diabetic retinopathy (DR) in a Northeastern Chinese population with type 2 diabetes.

Methods:

A total of 1322 subjects from the Fushun Diabetic Retinopathy Cohort Study were enrolled. Systolic blood pressure (SBP), diastolic blood pressure (DBP), and intraocular pressure (IOP) were recorded. MOPP was calculated by the following formula: MOPP = 2/3 [DBP + 1/3 (SBP − DBP)] – IOP, and CSFP was estimated according to the following formula: CSFP = 0.44 × body mass index + 0.16 × DBP − 0.18 × age − 1.91. New development, progression, and regression of DR were graded based on fundus photographs at baseline and during follow-up examinations with a mean interval of 21.2 months using the modified Early Treatment Diabetic Retinopathy Study criteria.

Results:

Increasing MOPP was associated with the incidence of DR in the multivariate model (per 1-mmHg increase: relative risk [RR], 1.06; 95% confidence interval [CI], 1.02–1.10; P = 0.007) and showed a borderline negative association with DR regression (per 1-mmHg increase: RR [95% CI]: 0.98 [0.97–1.00], P = 0.053). However, MOPP was not associated with progression of DR. CSFP was not associated with new development, progression, or regression of DR.

Conclusion:

The MOPP, but not the CSFP, was found to influence the development but not the progression of DR in this Northeastern Chinese cohort.
Scleral Suture Intraocular Lens Fixation under Microscope–Intraoperative Optical Coherence Tomography
Authors: Shi Jiemei , Cheng Tongjie , Zhao Hongmei , Fan Jinyu , Jiang Tianliang , Tang Ning , Li Yunyao , Wu Kaicheng , Shi Guohua , Jiang Chunhui
Published: March 2023

Purpose:

The aim of this study was to evaluate the accessibility and potential value of intraoperative optical coherence tomography (iOCT) during scleral suture intraocular lens (IOL) fixation.

Methods:

This was a prospective cohort study in the Department of Ophthalmology, Eye and ENT Hospital, Fudan University, China. Seven eyes with insufficient capsular support and undergoing two-point scleral suture IOL fixation were included. The potential value of iOCT was evaluated, as well as the safety and efficacy of the surgery.

Results:

Seven eyes were included. With a tailor-made iOCT, the structure of the anterior segment could be clearly visualised during the surgery. Intraoperatively, iOCT helped locate the proper place for fixation and access the position of the IOL. After an average 4.43-month follow-up, the spherical equivalent changed significantly (P < 0.001), but the intraocular pressure, best-corrected visual acuity, and endothelial cell density remained unchanged (P > 0.05). The IOL was well-centered with a horizontal and vertical tilt of 0.74 ± 0.60° and 1.13 ± 0.65°, and decentration of 0.28 ± 0.12 mm and 0.30 ± 0.13 mm. The estimated IOL-induced astigmatism was -0.11 dioptres (D) ± 0.46 D.

Conclusion:

Real-time high-resolution images of the anterior segment acquired by the iOCT helped the surgeon to achieve satisfactory results in scleral suture IOL fixation.
Adenotonsillectomy-related changes in systemic inflammation among children with obstructive sleep apnea
Authors: Huang Chung-Guei , Hsu Jen-Fu , Chuang Li-Pang , Li Hsueh-Yu , Fang Tuan-Jen , Huang Yu-Shu , Yang Albert C. , Lee Guo-She , Kuo Terry B.J. , Yang Cheryl C.H. , Lee Li-Ang , Chuang Hai-Hua
Published: March 2023

Background:

Adenotonsillar hypertrophy is the most common cause of pediatric obstructive sleep apnea (OSA). Although adenotonsillectomy considerably reduces OSA and systemic inflammation, whether and how systemic inflammation influences the effects of adenotonsillectomy on OSA has yet to be determined.

Methods:

This study investigated the associations between changes in anatomical variables, % changes in subjective OSA-18 questionnaire scores, % changes in 11 polysomnographic parameters, and % changes in 27 systemic inflammatory biomarkers in 74 children with OSA.

Results:

Fifty-six (75.6%) boys and 18 (24.4%) girls with the mean age of 7.4 ± 2.2 years and apnea-hypopnea index (AHI) of 14.2 ± 15.9 events/h were included in the statistical analysis. The mean period between before and after adenotonsillectomy was 5.6 ± 2.6 months. After adenotonsillectomy, the OSA-18 score, eight of 11 polysomnographic parameters, and 20 of 27 inflammatory biomarkers significantly improved (all p < 0.005). Notably, there were significant associations between change in tonsil size and % change in AHI (r = 0.23), change in tonsil size and % changes in interleukin-8 (IL-8) (r = 0.34), change in tonsil size and % change in and IL-10 (r = -0.36), % change in IL-8 and % change in C-C chemokine ligand 5 (CCL5) (r = 0.30), and % change in CCL5 and % change in AHI (r = 0.38) (all p < 0.005). Interestingly, % change in IL-8 and % change in CCL5 serially mediated the relationship between change in tonsil size and % change in AHI (total effect: β = 16.672, standard error = 8.274, p = 0.048).

Conclusion:

These preliminary findings suggest that systemic inflammation is not only a complication of OSA but also that it mediates the surgical effects, which may open avenues for potential interventions to reduce tonsil size and OSA severity through the regulation of IL-8 and CCL5.
Bosnian Paternal War Orphans
Authors: Kravić Nermina , Pajević Izet , Hasanović Mevludin , Karahasanović Nejla , Voracek Martin , Baca-Garcia Enrique , Dervic Kanita
Published: March 2023

More research on the medium- and long-term effects of childhood exposure to war, including orphanhood, is needed. We compared 50 orphans1 who lost their father during the war in Bosnia and Herzegovina (1992–1995) and 50 age- and sex-matched adolescents from two-parent families during 2011–2012 in terms of sociodemographic characteristics, behavioral/emotional problems, depression, resilience, maternal mental health, and perceived social support. The two groups differed on sociodemographic factors, that is, number of children, family composition, income, school grades, and refugeehood. Paternal war orphans did not differ in terms of adolescent mental health and resilience from their nonorphaned peers, controlling for sociodemographic variables. The mothers of orphans had comparably more posttraumatic psychopathology. As for perceived resources for social support, orphans identified those comparably more often among distant relatives and in the community, that is, religious officials and mental health professionals, and less often among siblings, paternal grandparents, paternal and maternal uncles/aunts, school friends and teachers. Our findings suggest that contextual factors may play an important role in orphans' postwar mental health.
Weber’s Law of perception is a consequence of resolving the intensity of natural scintillating light and sound with the least possible error
Authors: Pednekar Shourav , Krishnadas Arun , Cho Byunggu , Makris Nicholas C.
Published: March 2023

Efficient resolution of natural light and sound intensity is essential for organisms, systems and machines that rely on visual and auditory sensory perception to survive or function effectively in their environment. This resolution obeys Weber’s Law when the smallest resolvable change, a just-noticeable-difference, grows in direct proportion to the stimulus. Here, Weber’s Law is found to be a consequence of attaining the theoretical minimum mean-square error possible, the Cramer–Rao lower bound, in resolving the intensity of naturally scintillating light and sound. The finding is based on statistics from thousands of measurements of naturally scintillating environmental light and sound signals. Remarkably, just-noticeable-differences in light and sound intensity measured over decades of psychophysical experiments with artificial sources are also found to approximately attain the respective Cramer–Rao lower bounds. Human intensity resolution is in this way optimally adapted to the natural scintillation of light and sound. Pattern recognition by simple matched-filter correlation between measured and hypothetical images cancels natural scintillation. For intensity perception obeying Weber’s Law, this is found to be advantageous and statistically optimal because perceived scintillation is independent of the underlying signal pattern. A small visual patch change or acoustic signature truncation is shown to be lost in natural signal-dependent fluctuations if perception with constant intensity resolution is attempted.
Simulation and social network analysis provide insight into the acquisition of tool behaviour in hybrid macaques
Authors: Reeves Jonathan S. , Tan Amanda , Malaivijitnond Suchinda , Luncz Lydia V.
Published: March 2023

The pathways through which primates acquire skills are a central focus of cultural evolution studies. The roles of social and genetic inheritance processes in skill acquisition are often confounded by environmental factors. Hybrid macaques from Koram Island (Thailand) provide an opportunity to examine the roles of inheritance and social learning to skill acquisition within a single ecological setting. These hybrids are a cross between tool-using Burmese long-tailed (
Macaca fascicularis aurea
) and non-tool-using common long-tailed macaques (
Macaca fascicularis fascicularis
). This population provides an opportunity to explore the roles of social learning and inheritance processes while being able to exclude underlying ecological factors. Here, we investigate the roles of social learning and inheritance in tool use prevalence within this population using social network analysis and simulation. Agent-based modelling (ABM) is used to generate expectations for how social/asocial learning and inheritance structure the patterning in a social network. The results of the simulation show that various transmission mechanisms can be differentiated based on associations between individuals in a social network. The results provide an investigative framework for discussing tool use transmission pathways in the Koram social network. By combining ABM, network analysis, and behavioural data from the field we can investigate the roles social learning and inheritance play in tool acquisition of wild primates.
High taxonomic diversity and miniaturization in benthic communities under persistent natural CO
2
disturbances
Authors: González-Delgado Sara , Wangensteen Owen S. , Sangil Carlos , Hernández Celso A. , Alfonso Beatriz , Soto Ana Z. , Pérez-Portela Rocío , Mariani Stefano , Hernández José Carlos
Published: March 2023

Metabarcoding techniques have revolutionized ecological research in recent years, facilitating the differentiation of cryptic species and revealing previously hidden diversity. In the current scenario of climate change and ocean acidification, biodiversity loss is one of the main threats to marine ecosystems. Here, we explored the effects of ocean acidification on marine benthic communities using DNA metabarcoding to assess the diversity of algae and metazoans. Specifically, we examined the natural pH gradient generated by the Fuencaliente CO
2
vent system, located near La Palma Island (Canary Islands). High-resolution COI metabarcoding analyses revealed high levels of taxonomic diversity in an acidified natural area for the first time. This high number of species arises from the detection of small and cryptic species that were previously undetectable by other techniques. Such species are apparently tolerant to the acidification levels expected in future oceans. Hence and following our results, future subtropical communities are expected to keep high biodiversity values under an acidification scenario, although they will tend toward overall miniaturization due to the dominance of small algal and invertebrate species, leading to changes in ecosystem functions.
Transcriptional profiling of the response to starvation and fattening reveals differential regulation of autophagy genes in mammals
Authors: Galves Margarita , Sperber Michal , Amer-Sarsour Fatima , Elkon Ran , Ashkenazi Avraham
Published: March 2023

Nutrient deprivation (starvation) induced by fasting and hypercaloric regimens are stress factors that can influence cell and tissue homeostasis in mammals. One of the key cellular responses to changes in nutrient availability is the cell survival pathway autophagy. While there has been much research into the protein networks regulating autophagy, less is known about the gene expression networks involved in this fundamental process. Here, we applied a network algorithm designed to analyse omics datasets, to identify sub-networks that are enriched for induced genes in response to starvation. This enabled us to identify two prominent active modules, one composed of key stress-induced transcription factors, including members of the Jun, Fos and ATF families, and the other comprising autophagosome sub-network genes, including ULK1. The results were validated in the brain, liver and muscle of fasting mice. Moreover, differential expression analysis of autophagy genes in the brain, liver and muscle of high-fat diet-exposed mice showed significant suppression of GABARAPL1 in the liver. Finally, our data provide a resource that may facilitate the future identification of regulators of autophagy.
Characterization, and in vitro antibacterial activity of sulfated  polysaccharides from freshwater algae Cladophora crispata

Authors: jasem mohanad , Merai Abd- Alwahab , Nizam Adnan Ali
Published: March 2023

Barada River is characterized by an abundant growth of freshwater algae. Algae have been emerged as a new source for bioactive compounds, in this research Cladophoracrispata was cultivated in the outdoor method, and algae sulfated Polysaccharides (SPs) were extracted by ultrasonic-assisted extraction methods. After extraction, Gel filtration was used to purify the crude SPs; SPs compounds were determined and selected and we investigated the effect of SPs as antibacterial agents. the purified extract gave two fractions (F1 and F2).  The chemical components of both crude and purified SPs were then determind. The highest carbohydrate content (74.12%) and protein content (4.02%) was found in the crude extract, while the highest sulfate content (12.17%) was found in F2, and the highest uronic content (18.46%) was found in F1. Fourier transforms infrared Spectroscopy (FT-IR) was used for confirmed that the crud and fractions consist of sugar, uronic acids, protein unite, and sulfate groups. Both  F1, and F2 was found to consist of rhamnose, galactose, xylose, and ribose based on the High performance liquid chromatography (HPLC) separation. Each fraction showed an inhibitory effect on the gram-positive and gram-negative bacteria. F2 has the lowest minimum inhabit concentration (MIC) value against Enterobacteraerogenes and Staphylococcusaureus; where its MIC values were  28 and 10 (mg/ml) respectively. Algae polysaccharides had the most important interest due to their antibacterial properties, which is makes them included in pharmacy and food applications.
Acute hemorrhagic necrotizing encephalopathy associated with COVID-19 in a patient with liver cirrhosis
Authors: Singh Sweta , Singh Uday Shanker
Published: March 2023

COVID-19 emerging as a global pandemic is a complex disease presenting with multiorgan involvement.AHNE is a rarely reported phenomenon post COVID-19 infection but is a rapidly progressing, fatal, haemorrhagic necrosis of the CNS parenchyma. Here,we present a very interesting case of a cirrhotic male patient with acute hemorraghic necrotizing encephalopathy with COVID-19 infection. Diagnosis of AHNE requires a multimodality approach and high index of suspicion in a patient suffering from SARS CoV-2.Timely intervention and diagnosis may lead to a favourable outcome in the diagnosed cases.Future detailed studies in this direction may give an insight on this rare but important disease entity.
Nephrogenic diabetes insipidus in a geriatric patient affected by SARS-CoV-2: complexity of a diagnosis, complexity of a virus
Authors: Corich Maria Ada , Niero Michele , Ferretti Elisabetta , De Colle Paolo , Bernardi Stella , Ceschia Giuliano , Sanson Gianfranco , Zanetti Michela
Published: March 2023

Background: Coronavirus Disease-19 (COVID-19) has an important impact on the kidney, however, the involvement of the last part of the nephron has not been previously documented.
Methods: We present the case of a 71 years old man with respiratory failure in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pneumonia who, after about 20 days of hospitalization, presented the typical symptoms of diabetes insipidus. The water deprivation test led to the diagnosis of nephrogenic diabetes insipidus.
The analysis of the underlying cause was complex because of the patient’s pharmacological and medical history. In particular, potential alternative causes for nephrogenic diabetes insipidus including urinary tract infection and previous lithium therapy had to be ruled out.
Results: The sequence of pathognomonic events typical of diabetes insipidus associated with anamnestic, clinical and laboratory evidences strongly supported the diagnosis of nephrogenic diabetes insipidus due to SARS-CoV-2, rather than to other etiologies.
Conclusions: The collecting duct could represent a target for SARS-CoV-2 infection, directly or indirectly as a result of lesions of upstream portions of the nephron which would cascade into the distal segment. Other molecules, besides angiotensin 2 converting enzyme, might be involved in facilitating the viral aggression. The complexity of the geriatric patient shows the importance of a comprehensive approach which integrates a careful monitoring of clinical signs and symptoms,  laboratory and instrumental tests. This is especially important in the context of SARS-CoV-2 infection and in the management of its unexpected complications.
Safety and Immunogenicity of the NVX-CoV2373 Vaccine as a Booster in Adults Previously Vaccinated with the BBIBP-CorV Vaccine: An Interim Analysis
Authors: Toback Seth , Marchese Anthony M. , Warren Brandy , Ayman Sondos , Zarkovic Senka , ElTantawy Islam , Mallory Raburn M. , Rousculp Matthew , Almarzooqi Fahed , Piechowski-Jozwiak Bartlomiej , Bonilla Maria-Fernanda , Bakkour Agyad Ebrahim , Hussein Salah Eldin , Kaabi Nawal Al
Published: March 2023

This phase 3 observer-blind, randomized, controlled study was conducted in adults ≥18 years of age to assess the safety and immunogenicity of NVX-CoV2373 as a heterologous booster compared to BBIBP-CorV when utilized as a homologous booster. Approximately 1,000 participants were randomly assigned in a 1:1 ratio to receive a single dose of NVX-CoV2373 or BBIBP-CorV after prior vaccination with 2 or 3 doses of BBIBP-CorV. Solicited adverse events (AEs) were collected for 7 days after vaccination. Unsolicited AEs were collected for 28 days following the booster dose and serious adverse and adverse events of special interest (AESI) were collected throughout the study. For this interim analysis, anti-spike IgG and neutralizing antibodies against SARS-CoV-2 were measured at baseline, day 14, and day 28. The study achieved its primary non-inferiority endpoint and also demonstrated statistically higher neutralization responses of approximately 6-fold when NVX-CoV2373 was utilized as a heterologous booster compared with BBIBP-CorV as a homologous booster. Both vaccines had an acceptably low reactogenicity profile and no new safety concerns were found. Heterologous boosting with NVX-CoV2373 was a highly immunogenic and safe vaccine regimen in those previously vaccinated with BBIBP-CorV.
Rich Oleocanthal and Oleacein Extra Virgin Olive Oil and Inflammatory and Antioxidant Status in people with Obesity and Prediabetes. The APRIL Study: a Randomised, Controlled Crossover Study
Authors: Ruiz-Garcia Ignacio , Ortíz-Flores Rodolfo , Badia Rocío , Garcia-Borrego Aranzazu , García-Fernández María , Lara Estrella , Martín-Montañez Elisa , García-Serrano Sara , Valdés Sergio , Gonzalo Montserrat , Tapia-Guerrero María-José , Fernández-García José-Carlos , Sánchez-García Alicia , Muñoz-Cobos Francisca , Calderón-Cid Miguel , El-Bekay Rajaa , Covas María-Isabel , Rojo-Martínez Gemma , Olveira Gabriel , Romero-Zerbo Silvana-Yanina , Bermudez-Silva Francisco-Javier
Published: March 2023

Oleocanthal and oleacein are olive oil phenolic compounds with well known anti-inflammatory and anti-oxidant properties. The main evidence, however, is provided by experimental studies. Few human clinical trials have examined the health benefits of olive oils rich in these polyphenols. Our aim was to assess the health properties of rich oleocanthal and oleacein extra virgin olive oil (EVOO), compared to those of common olive oil (OO), in people with prediabetes and obesity. This was a randomised, double-blind, crossover trial done in people aged 40-65 years with obesity (BMI 30-40 kg/m2) and prediabetes (HbA1c 5.7-6.4%). The intervention consisted in substituting for 1 month the oil used for food, both raw and cooked, by EVOO or OO. No hypocaloric diet or changes in physical activity were recommended. The primary outcome was the inflammatory status. Secondary outcomes were the oxidative status, body weight, metabolic status and lipid profile. An ANCOVA model adjusted for age, sex and treatment administration sequence was used for the statistical analysis. 91 patients were enrolled (33 men and 58 women) and finished the trial. A decrease in interferon-γ was observed after EVOO treatment, reaching inter-treatment differences (P=0.041). Total antioxidant status increased and lipid and organic hydroperoxides decreased after EVOO treatment, the changes reaching significance compared to OO treatment (P<0.05). Decreases in weight, BMI and blood glucose (p<0.05) were found after treatment with EVOO and not with OO. In conclusion, treatment with EVOO rich in oleocanthal and oleacein differentially improved oxidative and inflammatory status in people with obesity and prediabetes.
Factors influencing the commissioning and implementation of health and social care interventions for people with dementia: commissioner and stakeholder perspectives
Authors: Tucker Rachael , Vickers Robert , Adams Emma , Burgon Clare , Lock Juliette , Goldberg Sarah , Gladman John , Masud Tahir , Orton Elizabeth , Timmons Stephen , Harwood Rowan H
Published: March 2023

Background

Despite several interventions demonstrating benefit to people living with dementia and their caregivers, few have been translated and implemented in routine clinical practice. There is limited evidence of the barriers and facilitators for commissioning and implementing health and social care interventions for people living with dementia. The aim of the current study was to explore the barriers and facilitators to commissioning and implementing a dementia friendly exercise and physical activity-based intervention (PrAISED (Promoting Activity, Stability and Independence in Early Dementia and Mild Cognitive Impairment)) in practice.

Methods

Qualitative semi-structured interviews were conducted with stakeholders from a range of backgrounds including individuals from universities, research centres, the voluntary and community sector, health and social care, and local government in England. The Consolidated Framework for Intervention Research (CFIR) was used to guide the design and analysis. Fourteen participants took part, including commissioning managers, service managers, partnership managers, charity representatives, commercial research specialists, academics/researchers, and healthcare professionals.

Results

Data were represented in 33 constructs across the five CFIR domains. Key barriers included cost/financing, the culture of commissioning, and available resources. Key facilitators included the adaptability of the intervention, cosmopolitanism/partnerships and connections, external policy and incentives, and the use of already existing (and untapped) workforces. Participants identified a need for greater support for people diagnosed with dementia and their caregivers immediately post dementia diagnosis.

Conclusion

Several barriers and facilitators for commissioning and implementing health and social care interventions for people with dementia were identified which need to be addressed. Recommended actions to facilitate the commissioning and implementation of dementia friendly services are: 1) map out local needs, 2) evidence the intervention including effectiveness and cost-effectiveness, 3) create/utilise networks with stakeholders, and 4) plan required resources.
Incorporating efficacy data from initial trials into subsequent evaluations: Application to vaccines against respiratory syncytial virus
Authors: Warren Joshua L. , Sundaram Maria , Pitzer Virginia E. , Omer Saad B. , Weinberger Daniel M.
Published: March 2023

Background

When a randomized controlled trial fails to demonstrate statistically significant efficacy against the primary endpoint, a potentially costly new trial would need to be conducted to receive licensure. Incorporating data from previous trials might allow for the conduct of more efficient follow-up trials to demonstrate efficacy, speeding the availability of effective vaccines.

Methods

Based on the outcomes from a failed trial of a maternal vaccine against respiratory syncytial virus (RSV), we simulated data for a new Bayesian group-sequential trial. The data were analyzed either ignoring data from the previous trial (i.e., weakly informative prior distributions) or using prior distributions that incorporate the historical data into the analysis. We evaluated scenarios where the efficacy in the new trial was the same, greater than, or less than the efficacy in the original trial. For each scenario, we evaluated the statistical power and type I error rate for estimating the vaccine effect following interim analyses.

Results

If a stringent threshold is used to control the type I error rate, the analyses that incorporated historical data had a small advantage over trials that did not. If control of type I error is less important (e.g., in a post-licensure evaluation), the incorporation of historical data can provide a substantial boost in efficiency.

Conclusions

Due to the need to control the type I error rate in trials used to license a vaccine, the incorporation of historical data provides little additional benefit in terms of stopping the trial early. However, these statistical approaches could be promising in evaluations that use real-world evidence following licensure.
Exposome approaches to assessing the association between urban land use environment and depressive symptoms in young adulthood: a FinnTwin12 cohort study
Authors: Wang Zhiyang , M.Whipp Alyce , Heinonen-Guzejev Marja , Júlvez Jordi , Kaprio Jaakko
Published: March 2023

Background

Depressive symptoms lead to a serious public health burden and are considerably affected by the environment. Land use, describing the urban living environment, has an impact on mental health, but complex relationship assessment is rare.

Objectives

We aimed to examine the complicated association between urban land use and depressive symptoms among young adults with differential land use environments, by applying multiple models, as an exposome study.

Methods

We included 1804 individual twins from the FinnTwin12 cohort, living in urban areas in 2012. There were 8 types of land use exposures in 3 buffer radii. The depressive symptoms were assessed through General Behavior Inventory (GBI) in young adulthood (mean age: 24.1). First, K- means clustering was performed to distinguish participants with differential land use environments. Then, linear elastic net penalized regression and eXtreme Gradient Boosting (XGBoost) were used to reduce dimensions or prioritize for importance and examine the linear and nonlinear relationships.

Results

Two clusters were identified with notable differences in the percentage of high-density residential, low-density residential, and natural land use. One is more typical of city centers, and another of suburban areas. A heterogeneous pattern in results was detected from the linear elastic net penalized regression model among the overall sample and the two separated clusters. Agricultural residential land use in a 100 m buffer contributed to GBI most (coefficient: 0.097) in the “suburban” cluster among 11 selected exposures. In the “city center” cluster, none of the land use exposures was associated with GBI. From the XGBoost models, we observed that ranks of the importance of land use exposures on GBI and their nonlinear relationships are also heterogeneous in the two clusters.

Discussion

As a hypothesis-generating study, we found heterogeneous linear and nonlinear relationships between urban land use environment and depressive symptoms under different contexts in pluralistic exposome analyses.
Looking under the lamp-post: quantifying the performance of contact tracing in the United States during the SARS-CoV-2 pandemic
Authors: Bayly Henry , Stoddard Madison , Van Egeren Debra , Murray Eleanor J , Raifman Julia , Chakravarty Arijit , White Laura F
Published: March 2023

Contact tracing forms a crucial part of the public-health toolbox in mitigating and understanding emergent pathogens and nascent disease outbreaks. Contact tracing in the United States was conducted during the pre-Omicron phase of the ongoing COVID-19 pandemic. This tracing relied on voluntary reporting and responses, often using rapid antigen tests (with a high false negative rate) due to lack of accessibility to PCR tests. These limitations, combined with SARS-CoV-2’s propensity for asymptomatic transmission, raise the question “how reliable was contact tracing for COVID-19 in the United States”? We answered this question using a Markov model to examine the efficiency with which transmission could be detected based on the design and response rates of contact tracing studies in the United States. Our results suggest that contact tracing protocols in the U.S. are unlikely to have identified more than 1.65% (95% uncertainty interval: 1.62%-1.68%) of transmission events with PCR testing and 0.88% (95% uncertainty interval 0.86%-0.89%) with rapid antigen testing. When considering an optimal scenario, based on compliance rates in East Asia with PCR testing, this increases to 62.7% (95% uncertainty interval: 62.6%-62.8%). These findings highlight the limitations in interpretability for studies of SARS-CoV-2 disease spread based on U.S. contact tracing and underscore the vulnerability of the population to future disease outbreaks, for SARS-CoV-2 and other pathogens.
Population genetic structure and range limits ofProstanthera cineolifera(Lamiaceae), a vulnerable shrub with a patchy distribution
Authors: Palsson Ruth L. , Telford Ian R.H. , Bruhl Jeremy J. , Andrew Rose L.
Published: March 2023

Integrating molecular data is essential for clarifying the distributions and genetic structures of species that have histories of misidentification and misapplication of names. There has been confusion about the species limits of the VulnerableProstanthera cineoliferawith respect to morphologically similar specimens in the Hunter Valley, New South Wales Australia and morphologically dissimilar specimens in the Lower Hawkesbury Valley New South Wales and from northeastern New South Wales. To test the species limits ofP. cineoliferaand related taxa specimens were collected from across the range and augmented with herbarium specimens. We used morphometric analysis of 18 morphological characters across 51 operational taxonomic units. Using the DArTseq reduced representation sequencing platform, 9,559 single-nucleotide polymorphisms (SNPs) across 122 individuals were recovered for molecular analysis. Both morphological and molecular analyses produced three concordant clusters (1)P. cineolifera, (2) a group sharing similarities withP. sp. Hawkesbury (B.J.Conn 2591), and (3) a group allied withP. lanceolataandP. ovalifolia. These results indicate that the specimens form northeastern New South Wales are more likely to beP. lanceolata, notP. cineolifera, and that specimens from the Lower Hawkesbury are of an undescribed species with the phrase nameP. sp. Hawkesbury (B.J.Conn 2591). WithinP. cineoliferathere was pronounced genetic differentiation among populations. Little evidence of inbreeding was observed, but the newly recognised, more isolated populations had the lowest genetic diversity. This study provides new information about the range of the species and its genetic structure that informs the conservation priorities for this species.
Phospho-seq: Integrated, multi-modal profiling of intracellular protein dynamics in single cells
Authors: Blair John D. , Hartman Austin , Zenk Fides , Dalgarno Carol , Treutlein Barbara , Satija Rahul
Published: March 2023

Cell signaling plays a critical role in regulating cellular behavior and fate. While multimodal single-cell sequencing technologies are rapidly advancing, scalable and flexible profiling of cell signaling states alongside other molecular modalities remains challenging. Here we present Phospho-seq, an integrated approach that aims to quantify phosphorylated intracellular and intranuclear proteins, and to connect their activity with cis-regulatory elements and transcriptional targets. We utilize a simplified benchtop antibody conjugation method to create large custom antibody panels for simultaneous protein and scATAC-seq profiling on whole cells, and integrate this information with scRNA-seq datasets via bridge integration. We apply our workflow to cell lines, induced pluripotent stem cells, and 3-month-old brain organoids to demonstrate its broad applicability. We demonstrate that Phospho-seq can define cellular states and trajectories, reconstruct gene regulatory relationships, and characterize the causes and consequences of heterogeneous cell signaling in neurodevelopment.
A role for N6-methyldeoxyadenosine inC. elegansmitochondrial genome regulation
Authors: Grub Lantana K. , Held James P. , Hansen Tyler J. , Schaffner Samantha H. , Canter Marleigh R. , Malagise Evi M. , Patel Maulik R.
Published: March 2023

Epigenetic modifications provide powerful means for transmitting information from parent to progeny. As a maternally inherited genome that encodes essential components of the electron transport chain, the mitochondrial genome (mtDNA) is ideally positioned to serve as a conduit for the transgenerational transmission of metabolic information. Here, we provide evidence that mtDNA ofC. eleganscontains the epigenetic mark N6-methyldeoxyadenosine (6mA). Bioinformatic analysis of SMRT sequencing data and methylated DNA IP sequencing data reveal thatC. elegansmtDNA is methylated at high levels in a site-specific manner. We further confirmed that mtDNA contains 6mA by leveraging highly specific anti-6mA antibodies. Additionally, we find that mtDNA methylation is dynamically regulated in response to antimycin, a mitochondrial stressor. Further, 6mA is increased innmad-1mutants and is accompanied by a significant decrease in mtDNA copy number. Our discovery paves the way for future studies to investigate the regulation and inheritance of mitochondrial epigenetics.