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In our article, we explore the transformative potential of Artificial Intelligence and Machine Learning in oculo-oncology, focusing on the diagnosis and management of ocular adnexal tumors. Delving into the intricacies of adnexal conditions such as conjunctival melanoma and squamous conjunctival carcinoma, the study emphasizes recent breakthroughs, such as Artificial Intelligence-driven early detection methods. While acknowledging challenges like the scarcity of specialized datasets and issues in standardizing image capture, the research underscores encouraging patient acceptance, as demonstrated in melanoma diagnosis studies. The abstract calls for overcoming obstacles, conducting clinical trials, establishing global regulatory norms and fostering collaboration between ophthalmologists and Artificial Intelligence experts. Overall, the article envisions Artificial Intelligence’s imminent transformative impact on ocular and periocular cancer diagnosis.

IntroductionThe Mnemonic Similarity Task (MST) is a widely used measure of individual tendency to discern small differences between remembered and presently presented stimuli. Significant work has established this measure as a reliable index of neurological and cognitive dysfunction and decline. However, questions remain about the neural and psychological mechanisms that support performance in the task.MethodsHere, we provide new insights into these questions by fitting seven previously-collected MST datasets (total N = 519), adapting a three-choice evidence accumulation model (the Linear Ballistic Accumulator). The model decomposes choices into automatic and deliberative components.ResultsWe show that these decomposed processes both contribute to the standard measure of behavior in this task, as well as capturing individual variation in this measure across the lifespan. We also exploit a delayed test/re-test manipulation in one of the experiments to show that model parameters exhibit improved stability, relative to the standard metric, across a 1 week delay. Finally, we apply the model to a resting-state fMRI dataset, finding that only the deliberative component corresponds to off-task co-activation in networks associated with long-term, episodic memory.DiscussionTaken together, these findings establish a novel mechanistic decomposition of MST behavior and help to constrain theories about the cognitive processes that support performance in the task.

BackgroundFor many young people, the transition from child to adult mental health services is a vulnerable time associated with treatment disengagement and illness progression. Providing service information and options to youth, appealing to them, and tailoring to their needs during this period could help overcome systematic barriers to a successful transition. We know little about how SMS text message–based interventions might be leveraged to support the motivational, informational, and behavioral needs of youth during this time. Ascertaining youth preferences for the content and functionality of an SMS text message service could inform prototype development. ObjectiveThis study investigated consensus preferences among youth on important content, technology features, and engagement supports to inform a transition-focused SMS text message service. MethodsA modified e-Delphi survey design was used to collect demographics, current levels of technology use, importance ratings on message content, preferred technical features, and barriers and enablers to engagement for youth in Canada aged 16-26 years who have accessed mental health services within the past 5 years. Survey items on content were categorized according to the information-motivation-behavioral skills (IMB) model. Survey items on technical features were categorized according to the persuasive system design (PSD) model. A predefined consensus rating matrix and descriptive statistics were used to characterize the sample. The high consensus threshold was 70%. ResultsA total of 100 participants, predominantly non-White (n=47, 47%), aged 20-26 years (n=59, 59%), and who had first accessed mental health services between the ages of 13 and 19 years (n=60, 60%), were selected. The majority (n=90, 90%) identified as daily SMS text message users. A high level of consensus on importance ratings was reported in 45% (9/20) of content items based on the IMB model. There were higher levels of consensus on importance ratings related to behavior domain items (3/3, 100%) than information domain items (4/9, 44%) or motivation domain items (2/8, 25%). A high level of consensus on importance ratings was reported in only 19% (4/21) of feature and functionality items based on the PSD model. Among PSD model categories, there was a high level of consensus on importance ratings in 8% (1/12) of the primary task support domain items and 100% (3/3) of the system credibility support domain items. None of the dialogue-support and social-support domain items met the high level of consensus thresholds. In total, 27% (27/100) of youth indicated that the most significant enabler for engaging with a transition-focused SMS text message intervention was the personalization of text messages. ConclusionsScientists developing next-generation SMS text messaging interventions for this population need to consider how levels of consensus on different features may impact feasibility and personalization efforts. Youth can (and should) play an integral role in the development of these interventions.

Cardiac arrest-induced global cerebral ischemia (GCI) results in profound cognitive impairment in survivors. Our prior work demonstrated persistent disruption of long-term potentiation (LTP) in hippocampal CA1 neurons, correlating with learning and memory deficits in a rodent model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Delayed inhibition of the Ca2+-permeable TRPM2 ion channel restored LTP post-CA/CPR, yet the mechanisms upstream of TRPM2 activation remain elusive. This study investigates CD38 as a potential regulator of TRPM2, highlighting a novel target to reverse hippocampal synaptic plasticity deficits after ischemia. We observe elevated levels of CD38 in activated astrocytes in the CA1 region of the hippocampus 7 days following CA/CPR in both male and female mice. Delayed inhibition of CD38 reverses hippocampal synaptic plasticity impairments at subacute timepoints after CA/CPR, phenocopying TRPM2 restoration of LTP. Our previous findings demonstrated that TRPM2 inhibition reverses the CA/CPR-induced enhancement of GABAA receptor (GABAAR) clustering, which contribute to ongoing LTP deficits. We, therefore, assessed the effect of CD38 on GABAergic inhibitory potentiation and find that inhibition of CD38 reverses GABAAR clustering in a TRPM2-dependent manner. In this study, we identify astroglial CD38 as a potential target and upstream regulator of the TRPM2 channel, offering a promising approach to restore hippocampal synaptic plasticity impairments following GCI through modulation of GABAergic signaling.

Mine lands contaminted with heavy metals pose environmental risks, and thus reclamation is paramount for improving soil, plant, animal, and ecosystem health. A metal-contaminated alluvial mine tailing, devoid of vegetation, received 224 ​Mg ​ha−1 of both lime and biosolids in 1998, and long-term reclamation success was quantified in 2019 with respect to soils, plants, and linkages to animals. Reclamation success was quantified using the Soil Management Assessment Framework (SMAF), in conjunction with bioavailable (0.01 ​M CaCl2 extractable) and plant-available (Mehlich-3 extractable) soil metal concentrations, X-ray absorption spectroscopy, plant metal concentrations, and plant quality characteristics. Results showed that all soil indicators were improved in successfully-reclaimed areas as compared to on-site degraded areas, including increases in soil aggregate stability, pH, plant-available P and K, soil organic C, potentially-mineralizable N, microbial biomass C and β-glucosidase activity and decreases in soil bulk density and electrical conductivity. Of indicators, unitless soil health scores were assigned based on the SMAF, with data suggesting that bulk density, wet aggregate stability, potentially- mineralizable N, microbial biomass C, pH, and electrical conductivity should be monitored in the future. The long-term effects of lime and biosolids application have improved soil physical, biological, and overall soil health. Plant metal concentrations have decreased by an order of magnitude since early reclamation, with most plant metal concentrations being tolerable for domestic livestock consumption. From an animal health perspective, feeding grasses from this site during latter parts of a growing season may need supplemental feed to provide greater protein and energy content, and to reduce potentially-harmful Cd concentrations from food chain bioaccumulation. However, a health concern exists based on soil bioavailable Cd and Zn concentrations that exceed ecological soil screening levels. Still, plants have stabilized the soil and acidity remains neutralized, leading to long-term improvements in soil health, with overall improved ecosystem health.

Background We investigated Leber hereditary optic neuropathy (LHON) families for variation in peripapillary retinal nerve fibre layer thickness and perfusion, and associated optic nerve dysfunction.Method A group of LHON-affected patients (n=12) and their asymptomatic maternal relatives (n=16) underwent examination including visual acuity (VA), visual-evoked-potential and optic nerve imaging including optical coherence tomography (OCT) and OCT angiography of the peripapillary retinal nerve fibre layer (RNFL). A control sample was also examined (n=10). The software imageJ was used to measure perfusion by assessing vessel density (VD), and statistical software ‘R’ was used to analyse data.Results The LHON-affected group (n=12) had significantly reduced peripapillary VD (median 7.9%, p=0.046). Overall, the LHON asymptomatic relatives (n=16) had no significant change in peripapillary VD (p=0.166), though three eyes had VD which fell below the derived normal range at 6% each, with variable VA from normal to blindness; LogMAR median 0, range 0–2.4. In contrast, RNFL thickness was significantly reduced in the LHON-affected group (median 51 µm, p=0.003), and in asymptomatic relatives (median 90 µm, p=0.01), compared with controls (median 101 µm). RNFL thinning had greater specificity compared with reduced perfusion for optic nerve dysfunction in asymptomatic carriers (92% vs 66%).Conclusion Overall, reduced peripapillary retinal nerve fibre layer perfusion was observed in those affected by LHON but was not reduced in their asymptomatic relatives, unlike RNFL thinning which was significantly reduced in both groups versus controls. The presence of RNFL changes was associated with signs of optic neuropathy in asymptomatic relatives.

Background: Infections lead to high mortality among patients on chronic dialysis; knowledge of multi-drug resistant infections is limited. The Centers for Disease Control and Prevention’s Emerging Infections Program (EIP) conducts laboratory- and population-based surveillance for carbapenem-resistant Enterobacterales (CRE) in 10 U.S. sites and carbapenem-resistant Acinetobacter baumannii (CRAB) in 9 U.S. sites. We investigated clinical characteristics, healthcare exposures, and outcomes of CRE and CRAB cases in persons on chronic dialysis from 2016-2021. Methods: Among EIP catchment-area residents on chronic dialysis, we defined a CRE case as the first isolation of Escherichia coli, Enterobacter cloacae complex, Klebsiella aerogenes (formerly Enterobacter aerogenes), Klebsiella oxytoca, Klebsiella pneumoniae, or Klebsiella variicola resistant to any carbapenem, from a normally sterile site or urine in a 30-day period. A CRAB case was defined as the first isolation of Acinetobacter baumannii complex resistant to any carbapenem (excluding ertapenem), from a normally sterile site or urine (or lower respiratory tract or wound since 2021) in a 30-day period. Medical records were reviewed. A case was considered colonized if the case culture had no associated infection type or colonization was documented in the medical record. Descriptive analyses, including analyses stratified by pathogen, were conducted. Results: Among 426 cases, 314 were CRE, and 112 were CRAB; most cases were male (235, 55.2%), Black (229, 53.8%), and 51-80 years old (320, 75.1%) (Table). An infection was associated with 363 (85.2%) case cultures; bloodstream infections (148; 40.8%), urinary tract infections (134; 36.9%), and pneumonia (17; 4.7%) were the most frequent. Overall, most cases had documented healthcare exposures (excluding outpatient dialysis) in the year before incident specimen collection, including: 366 (85.9%) hospitalizations, 235 (55.2%) surgeries, 209 (49.1%) long-term care facility stays, 54 (12.7%) long-term acute care facility stays. Additionally, 125 (29.3%) had an intensive care unit admission within the 7 days before incident specimen collection. Compared to CRE cases, a higher proportion of CRAB cases (a) had a long-term care facility stay (82/112 [73.2%] versus 127/314 [40.5%], P

Proper transport of RNAs to synapses is essential for localized translation of proteins in response to synaptic signals and synaptic plasticity. Alzheimer's disease (AD) is a neurodegenerative disease characterized by accumulation of amyloid aggregates and hyperphosphorylated tau neurofibrillary tangles followed by widespread synapse loss. To understand whether RNA synaptic localization is impacted in AD, we performed RNA sequencing on synaptosomes and brain homogenates from AD patients and cognitively healthy controls. This resulted in the discovery of hundreds of mislocalized mRNAs in AD among frontal and temporal brain regions. Similar observations were found in an APPswe/PSEN1dE9 mouse model. Furthermore, major differences were observed among circular RNAs (circRNAs) localized to synapses in AD including two overlapping isoforms of circGSK3β, one upregulated, and one downregulated. Expression of these distinct isoforms affected tau phosphorylation in neuronal cells substantiating the importance of circRNAs in the brain and pointing to a new class of therapeutic targets.

No abstract available.

Background Depression and anxiety are common in adolescents and have increased over the last decade. During that period, smartphone usage has become ubiquitous.Objectives The study aim was to assess the association between problematic smartphone usage (PSU) and anxiety.Methods Using a prospective mixed methods cohort study design, students aged 13–16 year old from two schools were enrolled regarding their smartphone use, mood and sleep via a semistructured questionnaire at baseline and week 4. The primary outcome was symptoms of anxiety (Generalised Anxiety Disorder Questionnaire, GAD-7) and exposure was PSU (Smartphone Addiction Scale Short Version). A linear regression was fitted to assess the change in anxiety. Thematic analysis of free-text responses was conducted.Findings The sample included 69 participants that were enrolled and followed up between 28 March and 3 June 2022. Of those with PSU, 44.4% exhibited symptoms of moderate to severe anxiety compared with 26.4% of those without PSU. There was a linear association between change in symptoms of anxiety and PSU β=0.18 (95% CI 0.04 to 0.32, p=0.013). Several themes were found: both positive and negative effects of smartphones on relationships; negative effects on school performance and productivity; mixed effects on mood; a desire to reduce the amount of time spent on smartphones.Conclusions Increased anxiety, depression and inability to sleep were seen in participants as their PSU score increased over time. Participants reported both positive and negative effects of smartphones and almost all used strategies to reduce use.Clinical implications Interventions need to be developed and evaluated for those seeking support.

Abstract Introduction Cabotegravir plus rilpivirine (CAB + RPV) is the first complete long‐acting (LA) regimen recommended for maintaining HIV‐1 virological suppression. Cabotegravir And Rilpivirine Implementation Study in European Locations (CARISEL) is an implementation–effectiveness study examining the implementation of CAB+RPV LA administered every 2 months (Q2M) in European HIV centres. We present staff study participant (SSP) perspectives on the administration of CAB+RPV LA over 12 months. Methods Eighteen clinics were randomized to one of two implementation support packages: standard arm (Arm‐S) or enhanced arm (Arm‐E). Arm‐S included video injection training and provider/patient toolkits. Additionally, Arm‐E included skilled wrap‐around team meetings, face‐to‐face injection training and continuous quality improvement (CQI) calls. SSPs completed surveys on the acceptability, appropriateness and feasibility of CAB+RPV LA as an intervention and its implementation into their clinics, as well as barriers and facilitators to implementation. All surveys were completed at Month (M)1 (baseline), M5 and M12; data collection was completed by February 2022. Qualitative data were obtained from semi‐structured interviews at M1, M5 and M12. The primary objective was assessed via formal statistical comparisons between study arms of the Acceptability of Implementation Measure, Implementation Appropriateness Measure and Feasibility of Implementation Measure surveys (1–5 Likert scale ranging from 1 = “completely disagree” to 5 = “completely agree”). Equivalent measures anchored to CAB+RPV LA as a therapy were also assessed. Results Seventy SSPs completed surveys and interviews at M1, 68 at M5 and 62 at M12. Mean acceptability/appropriateness/feasibility scores were ≥3.8 (out of 5) at M12 for implementation‐ and intervention‐based measures. An analysis of covariance showed no significant differences between study arms for these outcomes. Although barriers were noted, most SSPs were not overly concerned that these would impact implementation; concern about these anticipated barriers also decreased over time. At M12, 90.3% (n = 56/62) of SSPs held a positive opinion about CAB+RPV LA implementation. Qualitative interviews and CQI calls highlighted three top practices that supported implementation: implementation planning; education about CAB+RPV LA clinical efficacy; and education around administering injections and managing pain/discomfort after injections. Conclusions CARISEL demonstrated that CAB+RPV LA dosed Q2M was successfully implemented across a range of European locations, with SSPs finding implementation highly acceptable, appropriate and feasible. ClinicalTrials.gov number NCT04399551

Background Coproduction is defined as patients and clinicians collaborating equally and reciprocally in healthcare and is a crucial concept for quality improvement (QI) of health services. Learning Health Networks (LHNs) provide insights to integrate coproduction with QI efforts from programmes from various health systems.Objective We describe interventions to develop and maintain patient and family partner (PFP) coproduction, measured by PFP-reported and programme-reported scales. We aim to increase percentage of programmes with PFPs reporting active QI work within their programme, while maintaining satisfaction in PFP-clinician relationships.Methods Conducted in the Cystic Fibrosis Learning Network (CFLN), an LHN comprising over 30 cystic fibrosis (CF) programmes, people with CF, caregivers and clinicians cocreated interventions in readiness awareness, inclusive PFP recruitment, onboarding process, partnership development and leadership opportunities. Interventions were adapted by CFLN programmes and summarised in a change package for existing programmes and the orientation of new ones. We collected monthly assessments for PFP and programme perceptions of coproduction and PFP self-rated competency of QI skills and satisfaction with programme QI efforts. We used control charts to analyse coproduction scales and run charts for PFP self-ratings.Results Between 2018 and 2022, the CFLN expanded to 34 programmes with 52% having ≥1 PFP reporting active QI participation. Clinicians from 76% of programmes reported PFPs were actively participating or leading QI efforts. PFPs reported increased QI skills competency (17%–32%) and consistently high satisfaction and feeling valued in their work.Conclusions Implementing system-level programmatic strategies to engage and sustain partnerships between clinicians and patients and families with CF improved perceptions of coproduction to conduct QI work. Key adaptable strategies for programmes included onboarding and QI training, supporting multiple PFPs simultaneously and developing financial recognition processes. Interventions may be applicable in other health conditions beyond CF seeking to foster the practice of coproduction.

Summary: Highly pathogenic avian influenza (HPAI) viruses have spread at an unprecedented scale, leading to mass mortalities in birds and mammals. In 2023, a transatlantic incursion of HPAI A(H5N5) viruses into North America was detected, followed shortly thereafter by a mammalian detection. As these A(H5N5) viruses were similar to contemporary viruses described in Eurasia, the transatlantic spread of A(H5N5) viruses was most likely facilitated by pelagic seabirds. Some of the Canadian A(H5N5) viruses from birds and mammals possessed the PB2-E627K substitution known to facilitate adaptation to mammals. Ferrets inoculated with A(H5N5) viruses showed rapid, severe disease onset, with some evidence of direct contact transmission. However, these viruses have maintained receptor binding traits of avian influenza viruses and were susceptible to oseltamivir and zanamivir. Understanding the factors influencing the virulence and transmission of A(H5N5) in migratory birds and mammals is critical to minimize impacts on wildlife and public health.

Summary: Patients with tuberous sclerosis complex (TSC) develop multi-organ disease manifestations, with kidney angiomyolipomas (AML) and cysts being one of the most common and deadly. Early and regular AML/cyst detection and monitoring are vital to lower TSC patient morbidity and mortality. However, the current standard of care involves imaging-based methods that are not designed for rapid screening, posing challenges for early detection. To identify potential diagnostic screening biomarkers of AML/cysts, we performed global untargeted metabolomics in blood samples from 283 kidney AML/cyst-positive or -negative TSC patients using mass spectrometry. We identified 7 highly sensitive chemical features, including octanoic acid, that predict kidney AML/cysts in TSC patients. Patients with elevated octanoic acid have lower levels of very long-chain fatty acids (VLCFAs), suggesting that dysregulated peroxisome activity leads to overproduction of octanoic acid via VLCFA oxidation. These data highlight AML/cysts blood biomarkers for TSC patients and offers valuable metabolic insights into the disease.

Summary: Background: Autistic people are a high-risk group for self-harm and suicide. There are no evidence-based suicide prevention interventions developed specifically for autistic people. We undertook a pilot feasibility randomised controlled trial of autism adapted safety plans (AASP) to reduce self-harm and suicide for autistic people. Methods: This study took place in the United Kingdom and followed a randomised, two-arm, controlled design. Autistic adults (n = 53, mean age = 39, gender = 49% female, 29% not male or female) were recruited via third sector organisations and self-referral between 11.8.21 and 19.10.22. Participants were randomised without stratification to usual care with or without AASP. The AASP was completed by the autistic adults together with someone trained to support them. Research staff who completed follow-up assessments were blind to participant allocation. Primary outcomes were feasibility and acceptability. Participants were assessed at baseline, 1 and 6 months. Primary data were analysed under the intention to treat principle. Study protocol is published. The trial is closed to new participants. This study is registered with the ISRCTN registry, ISRCTN70594445. Findings: 53 participants consented, 49 were randomised to either AASP with usual care (n = 25) or usual care (n = 24). 68% of participants in the AASP arm were satisfied with the AASP and 41% rated it as useable. Feedback on the AASP and research methods were positive with suggested adaptations to some outcome measures. Retention and completion of outcomes measures in both arms was excellent, as was fidelity of delivery of the AASP. Interpretation: Study progression criteria were met, suggesting that the parameters of a future definitive trial of clinical and cost effectiveness of AASP to reduce self-harm and suicide in autistic adults are achievable, with minor recommended adaptions to outcome measures and AASP. Future research should explore the use of AASP in routine clinical practice. Funding: This study is funded by the NIHR [Public Health Research Programme (NIHR129196)].

Objectives: Given the evolving cannabis marketplace (e.g., products, marketing strategies), this study examined online cannabis marketing practices over time. Methods: In 2022 and 2023, researchers assessed website content (e.g., age verification, sales, delivery, warnings, ad content, promotional strategies) among 175 randomly-selected cannabis retailers’ websites across 5 US cities (Denver, Colorado; Seattle, Washington; Portland, Oregon; Las Vegas, Nevada; Los Angeles [LA], California, n=∼35/city). Analyses compared data from 2022 vs. 2023 and considered regulatory factors across cities. Results: Similar to 2022, in 2023, 76.6 % required age verification for site entry, 85.1 % used social media promotion, and 90.9 % offered online sales (82.4 % of which required age verification and 34.6 % offered delivery). There were significant (p 90 % in Denver, Las Vegas, LA), allowed discounts/price promotions (100 % in Denver and Las Vegas), or required health warnings (48–60 % in Seattle and LA vs.

Background: Epidermolysis bullosa (EB) is a rare, incurable genodermatosis that presents with blistering and skin fragility. Complications can be localised or generalised, limited to the skin or have systemic effects resulting in death. Caring for a child with this painful condition can have a profound effect on the quality of life of parents and the family. There is currently no published research on the lived experience of parents caring for a child with EB in a resource-limited environment in Africa. Method: This qualitative research used interpretative phenomenological analysis with the aim of understanding the lived experiences of parents caring for children with EB. Semi-structured interviews were conducted with 13 participants between May 2022 and October 2023. Guba’s framework of trustworthiness was used to ensure rigour. Results: Seven experiential themes with associated sub-themes were identified. The themes were (1) grappling with understanding EB, (2) the psychological experience, (3) living with the responsibility, (4) barriers to feeling supported, (5) changing relational dynamics, (6) experience of healthcare professionals and (7) parental needs. Conclusion: Parents caring for children with EB face emotional, physical, psychosocial and financial challenges. Addressing parents’ needs and concerns will go a long way in decreasing this burden. A biopsychosocial approach with an awareness of cultural context is essential for family-centred holistic EB care. Contribution: This is the first study in Africa that focussed on the lived experiences of parents caring for a child with EB.

Aims To investigate if estrogen agents as an adjunct to antipsychotic medication are effective at treating psychosis in post-and perimenopausal females. Methods A digital search focusing on controlled clinical trials was conducted. Studies were assessed for quality using the Cochrane Risk of Bias tool and GRADE system. The Joanna Briggs Institute (JBI) tools were used to critically appraise articles. The total Positive and Negative Symptom Scale (PANSS) scores were synthesised using a meta-analysis. Results Of the studies obtained (n = 11), two used estrogen HT as an augmentation agent, and nine used the SERM Raloxifene. Quality review and critical appraisal found inconsistencies in data and publication bias favouring trials that include Raloxifene. Meta-analysis results indicate Raloxifene plus antipsychotic did perform better than placebo [Std diff in means total = 0.340 (95% CI) p = 0.001] with a small effect size (g = 0.3392). Conclusion Though research appears promising, recommendations for the use of estrogen agent augmentation cannot be made at this time as more clinical trials that include a diverse range of treatments are needed.

OBJECTIVES:. The COVID-19 pandemic precipitated a significant transformation of scientific journals. Our aim was to determine how critical care (CC) journals and their impact may have evolved during the COVID-19 pandemic. We hypothesized that the impact, as measured by citations and publications, from the field of CC would increase. DESIGN:. Observational study of journal publications, citations, and retractions status. SETTING:. All work was done electronically and retrospectively. SUBJECTS:. The top 18 CC journals broadly concerning CC, and the top 5 most productive CC journals on the SCImago list. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. For the top 18 CC journals and specifically Critical Care Medicine (CCM), time series analysis was used to estimate the trends of total citations, citations per publication, and publications per year by using the best-fit curve. We used PubMed and Retraction Watch to determine the number of COVID-19 publications and retractions. The average total citations and citations per publication for all journals was an upward quadratic trend with inflection points in 2020, whereas publications per year spiked in 2020 before returning to prepandemic values in 2021. For CCM total publications trend downward while total citations and citations per publication generally trend up from 2017 onward. CCM had the lowest percentage of COVID-related publications (15.7%) during the pandemic and no reported retractions. Two COVID-19 retractions were noted in our top five journals. CONCLUSIONS:. Citation activity across top CC journals underwent a dramatic increase during the COVID-19 pandemic without significant retraction data. These trends suggest that the impact of CC has grown significantly since the onset of COVID-19 while maintaining adherence to a high-quality peer-review process.

Infectious and toxicological risks are the main potential hazards that operators of Human Milk Banks (HMBs) encounter and must eliminate. HMBs are trying to implement procedures that allow to manage and sanitize human milk without altering significantly its nutritional and biologically protective components, obtaining a product characterized by a valid balance between safety and biological quality. The history of human milk processing is linked to the origins of HMBs themselves. And although other forms of sterilization were used originally, pasteurization soon became the recognized most effective means for sanitizing milk: all the milk that arrives at the HMB must be pasteurized. Holder pasteurization (HoP) is the most used methodology, and it is performed using low temperature and long time (+62.5°C for 30 min). With HoP some bioactive milk components are lost to varying degrees, but many other precious bioactive compounds are completely or partially preserved. To improve the quality of human milk processed by HMBs, maintaining in the meantime the same microbiological safety offered by HoP, new technologies are under evaluation. At present, High-Temperature Short-Time pasteurization (HTST) and High-Pressure Processing are the most studied methodologies. HTST is already utilized in some HMBs for daily practical activity and for research purposes. They seem to be superior to HoP for a better preservation of some nutritional and biologically protective components. Freeze-drying or lyophilization may have advantages for room temperature storage and transportation. The aim of this study is to evaluate the advancement regarding the processing of DHM with a literature search from 2019 to 2022. The effects of the new technologies on safety and quality of human milk are presented and discussed. The new technologies should assure microbiological safety of the final product at least at the same level as optimized HoP, with an improved preservation of the nutritional and bioactive components of raw human milk.

Abstract Infectious etiologies have previously been proposed as causes of both melanoma and non‐melanoma skin cancer. This exploratory overview explains and presents the evidence for the hypothesis that a microorganism excreted in infected ruminant animal feces, Mycobacterium avium subspecies paratuberculosis (MAP), is the cause of some cases of cutaneous melanoma (CM). Occupational, residential, and recreational contact with MAP‐contaminated feces, soil, sand, and natural bodies of water may confer a higher rate of CM. Included in our hypothesis are possible reasons for the differing rates and locations of CM in persons with white versus nonwhite skin, why CM develops underneath nails and in vulvar skin, why canine melanoma is an excellent model for human melanoma, and why the Bacille Calmette‐Guérin (BCG) vaccine has demonstrated efficacy in the prevention and treatment of CM. The pathogenic mechanisms and etiologic aspects of MAP, as a transmittable agent underlying CM risk, are carefully deliberated in this paper. Imbalances in gut and skin bacteria, genetic risk factors, and vaccine prevention/therapy are also discussed, while acknowledging that the evidence for a causal association between MAP exposure and CM remains circumstantial.

One primary goal of laboratory animal welfare science is to provide a comprehensive severity assessment of the experimental and husbandry procedures or conditions these animals experience. The severity, or degree of suffering, of these conditions experienced by animals are typically scored based on anthropocentric assumptions. We propose to (a) assess an animal’s subjective experience of condition severity, and (b) not only rank but scale different conditions in relation to one another using choice-based preference testing. The Choice-based Severity Scale (CSS) utilizes animals’ relative preferences for different conditions, which are compared by how much reward is needed to outweigh the perceived severity of a given condition. Thus, this animal-centric approach provides a common scale for condition severity based on the animal’s perspective. To assess and test the CSS concept, we offered three opportunistically selected male rhesus macaques (Macaca mulatta) choices between two conditions: performing a cognitive task in a typical neuroscience laboratory setup (laboratory condition) versus the monkey’s home environment (cage condition). Our data show a shift in one individual’s preference for the cage condition to the laboratory condition when we changed the type of reward provided in the task. Two additional monkeys strongly preferred the cage condition over the laboratory condition, irrespective of reward amount and type. We tested the CSS concept further by showing that monkeys’ choices between tasks varying in trial duration can be influenced by the amount of reward provided. Altogether, the CSS concept is built upon laboratory animals’ subjective experiences and has the potential to de-anthropomorphize severity assessments, refine experimental protocols, and provide a common framework to assess animal welfare across different domains.

Abstract Introduction Consumer‐oriented health information technologies (CHIT) such as the patient portal have a growing role in care delivery redesign initiatives such as the Learning Health System. Care partners commonly navigate CHIT demands alongside persons with complex health and social needs, but their role is not well specified. Methods We assemble evidence and concepts from the literature describing interpersonal communication, relational coordination theory, and systems‐thinking to develop an integrative framework describing the care partner's role in applied CHIT innovations. Our framework describes pathways through which systematic engagement of the care partner affects longitudinal work processes and multi‐level outcomes relevant to Learning Health Systems. Results Our framework is grounded in relational coordination, an emerging theory for understanding the dynamics of coordinating work that emphasizes role‐based relationships and communication, and the Systems Engineering Initiative for Patient Safety (SEIPS) model. Cross‐cutting work systems geared toward explicit and purposeful support of the care partner role through CHIT may advance work processes by promoting frequent, timely, accurate, problem‐solving communication, reinforced by shared goals, shared knowledge, and mutual respect between patients, care partners, and care team. We further contend that systematic engagement of the care partner in longitudinal work processes exerts beneficial effects on care delivery experiences and efficiencies at both individual and organizational levels. We discuss the utility of our framework through the lens of an illustrative case study involving patient portal‐mediated pre‐visit agenda setting. Conclusions Our framework can be used to guide applied embedded CHIT interventions that support the care partner role and bring value to Learning Health Systems through advancing digital health equity, improving user experiences, and driving efficiencies through improved coordination within complex work systems.

Summary: Background: Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) and Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) improve cardiorenal outcomes in patients with type 2 diabetes. Equitable use of SGLT2i and GLP-1 RA has the potential to reduce racial and ethnic health disparities. We evaluated trends in pharmacy dispensing of SGLT2i and GLP-1 RA by race and ethnicity. Methods: Retrospective cohort study of patients (≥18 years) with type 2 diabetes using 2014–2022 electronic health record data from six US care delivery systems. Entry was at earliest pharmacy dispensing of any type 2 diabetes medication. We used multivariable logistic regression to evaluate the association between pharmacy dispensing of SGLT2i and GLP1-RA and race and ethnicity. Findings: Our cohort included 687,165 patients (median 6 years of dispensing data; median 60 years; 0.3% American Indian/Alaska Native (AI/AN), 16.6% Asian, 10.5% Black, 1.4% Hawaiian or Pacific Islander (HPI), 31.1% Hispanic, 3.8% Other, and 36.3% White). SGLT2i was lower for AI/AN (OR 0.80, 95% confidence interval 0.68–0.94), Black (0.89, 0.86–0.92) and Hispanic (0.87, 0.85–0.89) compared to White patients. GLP-1 RA was lower for AI/AN (0.78, 0.63–0.97), Asian (0.50, 0.48–0.53), Black (0.86, 0.83–0.90), HPI (0.52, 0.46–0.57), Hispanic (0.69, 0.66–0.71), and Other (0.78, 0.73–0.83) compared to White patients. Interpretation: Dispensing of SGLT2is, and GLP-1 RAs was lower in minority group patients. There is a need to evaluate approaches to increase use of these cardiorenal protective drugs in patients from racial and ethnic minority groups with type 2 diabetes to reduce adverse cardiorenal outcomes and improve health equity. Funding: Patient-Centered Outcomes Research Institute and National Institutes of Health.

Mounting evidence indicates that blueberry consumption is associated with a variety of health benefits. It has been suggested that regular consumption of blueberries can support and/or protect against cardiovascular disease and function, pre-diabetes and type 2 diabetes, and brain and cognitive function in individuals with health conditions and age-related decline. Further, mechanistic investigations highlight the role of blueberry anthocyanins in mediating these health benefits, in part through interactions with gut microbiota. Also, nutritional interventions with blueberries have demonstrated the ability to improve recovery following exercise-induced muscle damage, attributable to anti-inflammatory effects. Despite these advancements in blueberry health research, research gaps persist which affects the generalizability of findings from clinical trials. To evaluate the current state of knowledge and research gaps, a blueberry health roundtable with scientific experts convened in Washington, DC (December 6–7, 2022). Discussions centered around five research domains: cardiovascular health, pre-diabetes and diabetes, brain health and cognitive function, gut health, and exercise recovery. This article synthesizes the outcomes of a blueberry research roundtable discussion among researchers in these domains, offering insights into the health benefits of blueberries and delineating research gaps and future research directions.

Summary: The ancestral gamete fusion protein, HAP2/GCS1, plays an essential role in fertilization in a broad range of taxa. To identify factors that may regulate HAP2/GCS1 activity, we screened mutants of the ciliate Tetrahymena thermophila for behaviors that mimic Δhap2/gcs1 knockout phenotypes in this species. Using this approach, we identified two new genes, GFU1 and GFU2, whose products are necessary for membrane pore formation following mating type recognition and adherence. GFU2 is predicted to be a single-pass transmembrane protein, while GFU1, though lacking obvious transmembrane domains, has the potential to interact directly with membrane phospholipids in the cytoplasm. Like Tetrahymena HAP2/GCS1, expression of GFU1 is required in both cells of a mating pair for efficient fusion to occur. To explain these bilateral requirements, we propose a model that invokes cooperativity between the fusion machinery on apposed membranes of mating cells and accounts for successful fertilization in Tetrahymena’s multiple mating type system.

Summary: Early modern humans lived as hunter-gatherers for millennia before agriculture, yet the genetic adaptations of these populations remain a mystery. Here, we investigate selection in the ancient hunter-gatherer-fisher Jomon and contrast pre- and post-agricultural adaptation in the Japanese archipelago. Building on the successful validation of imputation with ancient Asian genomes, we identify selection signatures in the Jomon, particularly robust signals from KITLG variants, which may have influenced dark pigmentation evolution. The Jomon lacks well-known adaptive variants (EDAR, ADH1B, and ALDH2), marking their emergence after the advent of farming in the archipelago. Notably, the EDAR and ADH1B variants were prevalent in the archipelago 1,300 years ago, whereas the ALDH2 variant could have emerged later due to its absence in other ancient genomes. Overall, our study underpins local adaptation unique to the Jomon population, which in turn sheds light on post-farming selection that continues to shape contemporary Asian populations.

Five scholarly practitioners in an educational leadership for social justice doctoral program share their intentional, community-minded pivots during a global pandemic that disrupted their Dissertations in Practice (DiP). Embodying their Ed.D. program's CPED framework (Carnegie Project on the Education Doctorate, 2019), the authors, at varying stages in the dissertation process, sought inventive solutions to COVID-19-related challenges that included the development of a new topic and research questions, adjusting study settings and participant pools, and embracing new methodologies to account for virtual-only approaches. Although uncertain how the global health crises would impact their DiP, by fostering a shared sense of community, the authors became critical friends, supporting each other in their personal, professional, and academic lives. Each narrative highlights the potential of oppositional praxis of threading identities of practice, reflection, and research--to respond creatively to the needs of their diverse research communities with compassion, vision, and agility.

IntroductionIn response to reducing cigarette nicotine content, people who smoke could attempt to compensate by using more cigarettes or by puffing on individual cigarettes with greater intensity. Such behaviors may be especially likely under conditions where normal nicotine content (NNC) cigarettes are not readily accessible. The current within-subject, residential study investigated whether puffing intensity increased with very low nicotine content (VLNC) cigarette use, relative to NNC cigarette use, when no other nicotine products were available.Aims and methodsSixteen adults who smoke daily completed two four-night hotel stays in Charleston, South Carolina (United States) in 2018 during which only NNC or only VLNC cigarettes were accessible. We collected the filters from all smoked cigarettes and measured the deposited solanesol to estimate mouth-level nicotine delivery per cigarette. These estimates were averaged within and across participants, per each 24-h period. We then compared the ratio of participant-smoked VLNC and NNC cigarette mouth-level nicotine with the ratio yielded by cigarette smoking machines (when puffing intensity is constant).ResultsAverage mouth-level nicotine estimates from cigarettes smoked during the hotel stays indicate participants puffed VLNC cigarettes with greater intensity than NNC cigarettes in each respective 24-h period. However, this effect diminished over time (p < .001). Specifically, VLNC puffing intensity was 40.0% (95% CI: 29.9, 53.0) greater than NNC puffing intensity in the first period, and 16.1% (95% CI: 6.9, 26.0) greater in the fourth period.ConclusionAverage puffing intensity per cigarette was elevated with exclusive VLNC cigarette use, but the extent of this effect declined across four days.ImplicationsIn an environment where no other sources of nicotine are available, people who smoke daily may initially attempt to compensate for cigarette nicotine reduction by puffing on individual cigarettes with greater intensity. Ultimately, the compensatory behavior changes required to achieve usual nicotine intake from VLNC cigarettes are drastic and unrealistic. Accordingly, people are unlikely to sustain attempts to compensate for very low cigarette nicotine content.

INTRODUCTION: Malawi is rapidly closing the gap in achieving the UNAIDS 95-95-95 targets, with 90% of people living with HIV in Malawi aware of their status. As we approach epidemic control, interventions to improve coverage will become more costly. There is, therefore, an urgent need to identify innovative and low-cost strategies to maintain and increase testing coverage without diverting resources from other HIV services. The objective of this study is to model different combinations of facility-based HIV testing modalities and determine the most cost-effective strategy to increase the proportion of men and youth testing for HIV. METHODS: A data-driven individual-based model was parameterized with data from a community-representative survey (socio-demographic, health service utilization and HIV testing history) of men and youth in Malawi (data collected August 2019). In total, 79 different strategies for the implementation of HIV self-testing (HIVST) and provider-initiated-testing-and-counselling at the outpatient department (OPD) were evaluated. Outcomes included percent of men/youth tested for HIV in a 12-month period, cost-effectiveness and human resource requirements. The testing yield was assumed to be constant across the scenarios. RESULTS: Facility-based HIVST offered year-round resulted in the greatest increase in the proportion of men and youth tested in the OPD (from 45% to 72%-83%), was considered cost-saving for HIVST kit priced at $1.00, and generally reduced required personnel as compared to the status quo. At higher HIVST kit prices, and more relaxed eligibility criteria, all scenarios that considered year-round HIVST in the OPD remained on the cost-effectiveness frontier. CONCLUSIONS: Facility-based HIVST is a cost-effective strategy to increase the proportion of men/youth tested for HIV in Malawi and decreases the human resource requirements for HIV testing in the OPD-providing additional healthcare worker time for other priority healthcare activities.

Bringing effective, research-based literacy interventions into the classroom is challenging, especially given the cultural and linguistic diversity of today's classrooms. We examined the promise of Assessment-to-Instruction (A2i) technology redesigned to be used at scale to support teachers' implementation of the individualized student instruction (ISI) intervention from kindergarten through third grade. In seven randomized controlled trials, A2i and ISI have demonstrated efficacy. However, the research version of A2i was not scalable. In order to bring A2i to scale in schools serving linguistically diverse students, we carried out the current study across two phases. This study represents both an exploration of what it takes to bring an educational intervention to scale (Phase 1) and a quasi-experiment on the literacy outcomes of learners whose teachers used the technology (Phase 2). We integrated assessments of vocabulary, word decoding, and reading comprehension; revised the A2i algorithms to account for the constellation of skills English learners (ELs) bring to the classroom; updated the user interfaces and added new graphic features; and improved bandwidth and stability of the technology. Findings were mixed, including several non-significant results, a marginally significant intent-to-treat effect on word reading in kindergarten and first grade for English monolingual students and ELs, and one significant interaction effect, which suggested ELs and students with less developed reading skills in second and third grade benefitted most from the intervention. With some caution, we conclude that A2i demonstrates potential to be used at scale and promise of effectiveness for improving code-focused skills for diverse learners.