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Alcohol misuse ranks among the leading causes of preventable death worldwide. Therefore, discovering measures that can predict hazardous drinking is critical. The delay discounting paradigm—which assesses relative preference for immediate rewards over larger, later rewards—has frequently been used as a proxy for impulsive choice, but it does not capture how long someone is willing to wait for delayed rewards when the arrival time is uncertain. In contrast, a newer willingness‐to‐wait task measures how long someone is willing to wait for a delayed reward of uncertain timing before giving up. We hypothesized that performance in this willingness‐to‐wait task would be associated with drinking severity and that this task may even outperform delay discounting as a predictor of drinking severity. We pooled data from multiple studies of mostly college‐aged adult participants. Drinking severity was assessed with the Alcohol Use Disorders Identification Test. Willingness to wait under temporal uncertainty, but not delay discounting, was associated with severity of alcohol problems among participants who drank (n = 212). Individuals engaging in hazardous drinking were less willing to wait for rewards when delays were unknown than were individuals with low‐risk drinking habits. Thus, willingness to wait under temporal uncertainty may be an important predictor of problematic drinking. [ABSTRACT FROM AUTHOR]

Many wildlife species vary habitat selection across space, time, and behavior to maximize rewards and minimize risk. Multi‐scale research approaches that identify variation in wildlife habitat selection can highlight not only habitat preferences and risk tolerance but also movement strategies that afford coexistence or cause conflict with humans. Here, we examined how anthropogenic and natural features influenced coyote (Canis latrans) habitat selection in a mixed‐use, agricultural landscape in Mendocino County, California, USA. We used resource selection functions and hidden Markov models to test whether coyote selection for anthropogenic and natural features varied by time of day or by behavioral state (resting, foraging, and traveling). We found that coyotes avoided development, but, contrary to our expectations, coyotes selected for roads, agriculture, and areas with risk of human encounter and rifle use regardless of diel period or behavioral state. While traveling, coyotes increased selection for roads and avoided ruggedness, indicating that unpaved roads may enhance connectivity for coyotes in mixed‐use landscapes. Finally, we found that coyotes selected for mountain lion habitat when resting and at night, signifying that risk from natural predators was not a factor in habitat selection at coarse scales. Coyote habitat selection for places and times associated with human activity, without variation across scales, signals a potential for conflict if coyotes are perceived by people as a nuisance. [ABSTRACT FROM AUTHOR]

Objectives Methods Results Conclusion Clinical Significance To evaluate the color‐match with extracted natural teeth of three single‐shade universal composites, a group‐shade universal composite, and a highly translucent‐shade conventional composite.Twenty extracted human teeth were divided into light‐ and dark‐shade groups (n = 10, LSG and DSG). A preparation was restored with the 3 single‐shade universal composites, OMNICHROMA (OMC), Admira Fusion x‐tra U (AFU), and Essentia U (ESU); a highly translucent‐shade conventional composite, Tetric EvoCeram T (TEC‐T); and two shades of a group‐shade universal composite—Filtek Universal Restorative (FUR A1 and A4). Composites were photopolymerized, polished, and stored in water for 24 h. The ΔE00 value between the unprepared and restored surfaces was obtained using a spectrophotometer. Composite placement and measurements were repeated three times per tooth. Color differences were statistically analyzed with the within‐between‐subjects t‐test and repeated‐measures analysis of variance (ANOVA), followed by post hoc pairwise comparisons with a Bonferroni adjustment (α = 0.05).There were no statistically significant differences between OMC and FUR (A1 and A4). AFU and ESU showed significantly higher ΔE00 values than OMC and TEC‐T (p < 0.05). Single‐shade composites exhibited significantly higher ΔE00 values in the DSG than in the LSG except ESU (p < 0.05). None of the composites satisfied the criteria for an acceptable match (ΔE00 >1.8).OMC showed the same color matching ability as a group‐shade universal composite. A highly translucent‐shade conventional composite and OMC exhibited better color matching ability than other single‐shade composites. Overall, single‐shade universal composites performed better in lighter‐shaded teeth.Single‐shade universal composites have the potential to reduce chair time by eliminating shade selection in cavities with lighter‐shade teeth. Highly translucent incisal conventional composites also may be used if the appropriate shade of composite is not available. [ABSTRACT FROM AUTHOR]

Cannabinoid CB2 receptor agonists are in development as therapeutic agents, including for immune modulation and pain relief. Despite promising results in rodent preclinical studies, efficacy in human clinical trials has been marginal to date. Fundamental differences in ligand engagement and signalling responses between the human CB2 receptor and preclinical model species orthologues may contribute to mismatches in functional outcomes. This is a tangible possibility for the CB2 receptor in that there is a relatively large degree of primary amino acid sequence divergence between human and rodent. Here, we summarise CB2 receptor gene and protein structure, assess comparative molecular pharmacology between CB2 receptor orthologues, and review the current status of preclinical to clinical translation for drugs targeted at the CB2 receptor, focusing on comparisons between human, mouse and rat receptors. We hope that raising wider awareness of, and proposing strategies to address, this additional challenge in drug development will assist in ongoing efforts toward successful therapeutic translation of drugs targeted at the CB2 receptor. LINKED ARTICLES: This article is part of a themed issue Therapeutic Targeting of G Protein‐Coupled Receptors: hot topics from the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists 2021 Virtual Annual Scientific Meeting. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.14/issuetoc [ABSTRACT FROM AUTHOR]

Beside the well‐documented involvement of secondary somatosensory area, the cortical network underlying late somatosensory evoked potentials (P60/N60 and P100/N100) is still unknown. Electroencephalogram and magnetoencephalogram source imaging were performed to further investigate the origin of the brain cortical areas involved in late somatosensory evoked potentials, using sensory inputs of different strengths and by testing the correlation between cortical sources. Simultaneous high‐density electroencephalograms and magnetoencephalograms were performed in 19 participants, and electrical stimulation was applied to the median nerve (wrist level) at intensity between 1.5 and 9 times the perceptual threshold. Source imaging was undertaken to map the stimulus‐induced brain cortical activity according to each individual brain magnetic resonance imaging, during three windows of analysis covering early and late somatosensory evoked potentials. Results for P60/N60 and P100/N100 were compared with those for P20/N20 (early response). According to literature, maximal activity during P20/N20 was found in central sulcus contralateral to stimulation site. During P60/N60 and P100/N100, activity was observed in contralateral primary sensorimotor area, secondary somatosensory area (on both hemispheres) and premotor and multisensory associative cortices. Late responses exhibited similar characteristics but different from P20/N20, and no significant correlation was found between early and late generated activities. Specific clusters of cortical activities were activated with specific input/output relationships underlying early and late somatosensory evoked potentials. Cortical networks, partly common to and distinct from early somatosensory responses, contribute to late responses, all participating in the complex somatosensory brain processing. [ABSTRACT FROM AUTHOR]

Resting state functional magnetic resonance imaging (R‐fMRI) offers insight into how synchrony within and between brain networks is altered in disease states. Individual and disease‐related variability in intrinsic connectivity networks may influence our interpretation of R‐fMRI data. We used a personalized approach designed to account for individual variation in the spatial location of correlation maxima to evaluate R‐fMRI differences between Parkinson's disease (PD) patients who showed cognitive decline, those who remained cognitively stable and cognitively stable controls. We compared fMRI data from these participant groups, studied at baseline and 18 months later, using both network‐based statistics (NBS) and calculations of mean inter‐ and intra‐network connectivity within pre‐defined functional networks. The NBS analysis showed that PD participants who remained cognitively stable showed exclusively (at baseline) or predominantly (at follow‐up) increased intra‐network connectivity, whereas decliners showed exclusively reduced intra‐network and inter‐ (ventral attention and default mode) connectivity, in comparison with the control group. Evaluation of mean connectivity between all regions of interest (ROIs) within a priori networks showed that decliners had consistently reduced inter‐network connectivity for ventral attention, somatomotor, visual and striatal networks and reduced intra‐network connectivity for ventral attention network to striatum and cerebellum. These findings suggest that specific functional connectivity covariance patterns differentiate PD cognitive subtypes and may predict cognitive decline. Further, increased intra and inter‐network synchrony may support cognitive function in the face of PD‐related network disruptions. [ABSTRACT FROM AUTHOR]

Anti‐aging research has made significant strides in identifying treatments capable of extending lifespan across a range of organisms, from simple invertebrates to mammals. This review showcases the current state of anti‐aging interventions, highlighting the lifespan extensions observed in animal models through various treatments and the challenges encountered in translating these findings to humans. Despite promising results in lower organisms, the translation of anti‐aging treatments to human applications presents a considerable challenge. This discrepancy can be attributed to the increasing complexity of biological systems, species‐specific metabolic and genetic differences, and the redundancy of metabolic pathways linked to longevity. Our review focuses on analyzing these challenges, offering insights into the efficacy of anti‐aging mechanisms across species and identifying key barriers to their translation into human treatments. By synthesizing current knowledge and identifying gaps in translatability, this review aims to underscore the importance of advancing these therapies for human benefit. Bridging this gap is essential to assess the potential of such treatments in extending the human healthspan. [ABSTRACT FROM AUTHOR]

The vast majority of studies on discounting have focused on simple delayed outcomes, but most everyday decisions are more complicated. The present experiment focused on one such scenario, an iconic self‐control situation in which immediate gains are followed by delayed losses. The same participants were studied in all conditions to permit examination of individual differences in choice behavior using intercorrelations and factor analysis. Consistent with previous research, the hyperboloid model accurately described the form of the discounting function and discounting was not affected by the amount of the delayed loss when it was presented alone. However, replicating other studies, smaller delayed losses were discounted more steeply than larger ones when presented in combination with immediate gains. Exploratory factor analysis revealed two factors, one loading primarily on loss‐only conditions and the other loading primarily on conditions involving outcomes that combined gains and losses. These results imply that there are individual differences in how one combines gains and losses and that this characteristic of individual decision making might be an important predictor of decisions in the many everyday choice situations that involve complex outcomes. [ABSTRACT FROM AUTHOR]

The current study examined 98 participants' preferences for five pictorial stimuli. The researchers used a verbal multiple‐stimulus‐without‐replacement (VMSWO) preference assessment with each participant to identify high‐preference and low‐preference pictorial stimuli. Next, participants viewed each pictorial stimulus in a randomized order on a computer while using a hand dynamometer that measured the amount of force they exerted to increase or maintain the visual clarity of each image. The results indicate that over 75% of participants' force response ranks corresponded with participants' VMSWO high‐preference stimuli, VMSWO low‐preference stimuli, or both. The results of the current study provide further evidence for the use of conjugate schedules in the assessment of stimulus preference with potential for use as a reinforcer assessment. Implications along with directions for future research and limitations of the findings are discussed. [ABSTRACT FROM AUTHOR]

Background: Selective bromelain‐based enzymatic debridement (BED) has emerged as a valid alternative for the treatment of extensive burns, with Total Body Surface Area (TBSA) > 20%. Autologous skin grafting represents the procedure of choice but the scarcity of donor sites remains the main reconstructive challenge. The modified Meek micro‐grafting technique may represent a valid strategy to optimize the final outcome. Methods: A single‐cohort retrospective analysis was performed, involving nine burn patients (TBSA > 20%) who underwent both BED and subsequently modified Meek technique. Demographic and clinical data (mechanism of injury, surgical treatment, complications, necessity of re‐grafting, further surgery and esthetic outcome) were collected. Results: All patients had large burns of mixed and deep dermal thickness (first, second, and third degree). All burns were enzymatically debrided postadmission and covered by the modified Meek technique. Local infection due to poor general conditions was the main complication for all patients. All but two patients survived. The selectiveness of the enzymatic debridement and dermal preservation seemed to improve the quality of scars resulting from micro‐grafting. Evaluations performed at 12 ± 2 months postburn showed superior scar quality compared to areas treated with traditional (sheet/mesh) grafts. Conclusion: Combined BED and Meek techniques may provide an effective synergic combination for the treatment of extensive burns. Key messages: Combined bromelain‐based enzymatic debridement and Meek techniques may provide an effective synergic combination for the treatment of extensive burns, implying superior scar quality.Nine burn patients were evaluated, demographic, epidemiological and clinical data were collected.The selectiveness of the enzymatic debridement and dermal preservation seemed to improve the quality of scars resulting from micro‐grafting. [ABSTRACT FROM AUTHOR]

Objectives: To synthesize and appraise the evidence regarding the relationship between food insecurity and behaviours associated with dental caries development in adults and children in high‐income countries. Methods: A systematic review including observational studies assessing the association between food insecurity and selected dietary (free sugar consumption) and non‐dietary factors (tooth brushing frequency; use of fluoridated toothpaste; dental visiting; oral hygiene aids; type of toothbrush used; interdental cleaning frequency and mouthwash use) related to dental caries development in adults and children in high‐income countries. Studies specifically looking at food insecurity during the COVID‐19 pandemic were excluded. Searches were performed in MEDLINE, Embase, Global Health and Scopus from inception to 25 May 2023. Two authors screened the search results, extracted data and appraised the studies independently and in duplicate. Study quality was assessed using the Newcastle–Ottawa Scale (with modifications for cross‐sectional studies). Vote counting and harvest plots provided the basis for evidence synthesis. Results: Searches identified 880 references, which led to the inclusion of 71 studies with a total of 526 860 participants. The majority were cross‐sectional studies, conducted in the USA and reported free sugar consumption. Evidence for the association between food insecurity and free sugar intake from 4 cohort studies and 61 cross‐sectional studies including 336 585 participants was equivocal, particularly in the sugar‐sweetened beverage (SSB) consumption post‐hoc subgroup, where 20 out of 46 studies reported higher SSB consumption in food insecure individuals. There was consistent, but limited, evidence for reduced dental visiting in adults experiencing food insecurity compared to food secure adults from 3 cross‐sectional studies including 52 173 participants. The relationship between food insecurity and dental visiting in children was less clear (3 cross‐sectional studies, 138 102 participants). A single cross‐sectional study of 3275 children reported an association between food insecurity and reported failure to toothbrush the previous day. Conclusions: This review did not identify clear associations between food insecurity and behaviours commonly implicated in the development of dental caries that would explain why individuals experiencing food insecurity are more likely to have dental caries than those who have food security. There was some evidence of decreased dental visiting in adults experiencing food insecurity. Common methodological weaknesses across the evidence base related to the selection of participants or control of potentially confounding variables. Consequently, the quality of evidence for all outcomes was downgraded to very low. More research is needed to explore access to oral hygiene products and household environments conducive to habitual oral self‐care in food insecure populations. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Key points Gingival recession can be considered an undesirable condition that results in the exposure of the root surface. There are many techniques that can be employed to address gingival recession; however, they frequently involve a second surgical site. Other approaches have been introduced in the past to address this concern, and this case study discusses the use of a modified technique to achieve root coverage.A patient presented to the periodontics clinic with concerns regarding gingival recession. A modification to the semilunar technique was employed to address the recession, whereas double sling sutures were utilized to maintain the coronal repositioning of the flap.Maxillary central incisors initially presented with 2–3 mm of facial recession and root coverage was achieved by use of a modified surgical semilunar approach. No rebound noted over a 6‐month period, newly established gingival margin deemed clinically stable.This case study provides an alternative to addressing gingival recession in the maxillary anterior region, when <3 mm of recession is noted. Avoidance of a second surgical procedure and/or donor site is of particular benefit, as well as maintenance of the blood supply.Why is this case new information? There is insufficient evidence on the use of a modified wingspan incision design Phenotype modification with elimination of a second surgical site is most ideal for the patient. What are the keys to successful management of this case? Comprehensive diagnosis and proper case selection Meticulous flap management and adequate release to allow for repositioning without tension Appropriate use ofsuture and suturing technique. What are the primary limitations to success in this case? Thin periodontal phenotype Poor oral hygiene and plaque accumulation postoperatively Loss to follow‐up. [ABSTRACT FROM AUTHOR]

The VISTA enhancer database is a valuable resource for evaluating predicted enhancers in humans and mice. In addition to thousands of validated positive regions (VPRs) in the human and mouse genomes, the database also contains similar numbers of validated negative regions (VNRs). It is previously shown that the VPRs are on average half as long as predicted overlapping enhancers that are highly conserved and hypothesize that the VPRs may be truncated forms of long bona fide enhancers. Here, it is shown that like the VPRs, the VNRs also are under strong evolutionary constraints and overlap predicted enhancers in the genomes. The VNRs are also on average half as long as predicted overlapping enhancers that are highly conserved. Moreover, the VNRs and the VPRs display similar cell/tissue‐specific modification patterns of key epigenetic marks of active enhancers. Furthermore, the VNRs and the VPRs show similar impact score spectra of in silico mutagenesis. These highly similar properties between the VPRs and the VNRs suggest that like the VPRs, the VNRs may also be truncated forms of long bona fide enhancers. [ABSTRACT FROM AUTHOR]

Background Methods and Results Conclusion Key points While the nasal fossa and nasopalatine canal are recognized limitations for immediate implants in esthetic areas, the canalis sinuosus (CS) and its branches have been largely overlooked. Neglecting this anatomy can lead to sensory issues, pain, and implant failure underscores the necessity of meticulous pre‐surgical assessment and planning to mitigate risks and ensure implant success. This case highlights the need for comprehensive pre‐surgical evaluation and precise planning to minimize these complications and ensure successful implant outcomes in this scenario.A 41‐year‐old woman with a history of root perforation and external root resorption was referred for dental implant placement. Following clinical evaluation and computed tomography, the presence of an accessory canal of the CS was identified. After meticulous planning to avoid implant contact with this structure, ridge preservation was performed. After 6 months, the implant was successfully placed following guided osteotomy. The case demonstrates clinical and radiographic stability after 36 months of follow‐up.The correct diagnosis and planning, within a multidisciplinary team, can lead to successful implant placement in a challenging site with an anatomical variation. This study, to our knowledge, represents the first to propose an alternative treatment approach in the presence of CS in an esthetic region.Why is this case new information? This case emphasizes the importance of thorough pre‐surgical evaluation to mitigate potential complications related to the CS. It is the first, to our knowledge, to propose an alternative treatment approach in the presence of this anatomical variation in an esthetic region. What are the keys to successful management in this case? Comprehensive pre‐surgical evaluation, precise planning with detailed CBCT assessment to identify the CS, careful consideration of its anatomy during surgical intervention, knowledge of the limitations of tissue reconstructions, and precise clinical strategies to minimize associated complications. What are the primary limitations to success in this case? The need to position the implant with a safety margin from the CS led to implant positioning resulting in fenestration of the buccal bone plate, preventing its reconstruction due to the bone envelope's design, resulting in a discrepant gingival margin compared to the contralateral tooth, which did not allow for further crown lengthening due to a rather short root. [ABSTRACT FROM AUTHOR]

Topic: The COVID‐19 pandemic affected adolescents' physical and psychological health. There must be specific services to cater to the needs of adolescents during COVID‐19 in Indonesia. Lessons learned from previous pandemics will be beneficial for nurses and other health professionals to prepare services for future pandemics. Purpose: This mixed‐method study aimed to examine 459 Indonesian adolescents' health, literacy, preventive measures, and preferred health services during the COVID‐19 pandemic. This study also examines sociodemographics, respondent characteristics, health information sources, and media choices. Results: A total of 47.5% of adolescents knew about COVID‐19, 26.8% experienced physical health changes, and 61.7% considered wearing masks. Adolescent health information came from teachers (26.6%) and the Internet (32.9%). Psychological changes showed 67.8% irritation. Indonesians preferred online counseling (53.8%) and WhatsApp (45.8%) for pandemic health services. COVID‐19 literacy did not affect physical or mental health (p > 0.05). Conclusions: Most adolescents reported mental and physical health changes during COVID‐19. Our data suggest that adolescents' strong COVID−19 knowledge did not prevent anxiety and other psychological difficulties. The longitudinal studies could be utilized if pandemic demands social and physical distance. The government, as well as nurses, might utilize WhatsApp‐based remote online treatment for health services. Key points: Adolescents experienced physical and psychological changes during the COVID‐19 pandemic. Irritability is the most common change. There was no correlation between COVID‐19 literacy and physical and psychological wellness.Adolescents preferred online counseling and WhatsApp counseling as part of health services during the COVID‐19 pandemic.If there is a recurrence of a pandemic that necessitates social distancing, akin to COVID‐19, the government should contemplate including remote online counseling through WhatsApp as a component of their healthcare services delivery. [ABSTRACT FROM AUTHOR]

In April 2023, the National Cancer Institute offered a roadmap for cancer research to achieve Cancer Moonshot goals. To reach these goals requires making progress for all cancers, not just those that are most common. Achieving progress against rare cancers, as well as common cancers, requires involvement of large clinical research networks. In 2020, the Patient‐Centered Outcomes Research Institute (PCORI) launched an initiative on Conducting Rare Disease Research using PCORnet, the National Patient‐Centered Clinical Research Network. The purpose of this commentary is to introduce the broader community of cancer researchers to the PCORnet NET‐PRO study (comparing the effects of different treatment approaches for neuroendocrine tumors on patient‐reported outcomes) thereby demonstrating how researchers can use the PCORnet infrastructure to conduct large‐scale patient‐centered studies of rare cancers. Achieving progress against rare cancers requires involvement of large clinical research networks. This commentary showcases the NET‐PRO study (comparing the effects of different treatment approaches for neuroendocrine tumors on patient‐reported outcomes) to demonstrate how cancer researchers can conduct large‐scale patient‐centered studies of rare cancers using PCORnet. [ABSTRACT FROM AUTHOR]

A novel approach to melanoma diagnosis—in vivo molecular skin fluorescence imaging (mSFI)—was developed to identify premalignant changes in the form of tissue remodeling related to melanoma development in humans by imaging the proximal microenvironment of lesions. The method was tested using a fluorescent peptide (ORL‐1) which binds to αvβ3 integrin, a molecule associated with invasive melanoma development. A cut off score of 7 was established, differentiating melanomas from nonmelanoma nevi with 100% sensitivity, and 95.7% specificity, while identifying dysplastic nevi with the potential for melanoma development. Summary In vivo molecular skin fluorescent imaging (mSFI) differentiates between concerning and non‐concerning nevi identifying microenvironmental tissue remodeling changes associated with melanoma development. This method has the potential to improve pigmented lesion assessment during clinical evaluation, consequently improving the selection of lesions for biopsy. [ABSTRACT FROM AUTHOR]

Whereas multifocality typically concerns papillary thyroid carcinoma (PTC) without specification of intrathyroidal metastatic or independent nature of tumor foci, the designation of the latter as Multi‐UniFocal (MUF) may be relevant for select cases. A case series involving multifocal thyroid lesions with divergent histopathological morphology and/or molecular profile, with molecular evaluation of multiple individual tumor foci per patient based on a next‐generation sequencing approach, was retrospectively reviewed. Twenty‐five patient cases with multifocal thyroid lesions suggestive of MUF, with 2–6 (median 3) tumor foci per patient, were described. Tumor lesions comprised diverse histopathology, including PTC, (E)FVPTC, NIFTP, FA, FTC, and oncocytic. Morphologically similar and/or diverse tumor foci harbored different molecular alterations (suggestive of non‐shared clonality); with(out) coexistent similar foci harboring identical molecular alterations; or (partly) shared molecular alterations. MUF was associated with chronic lymphocytic thyroiditis in almost half of the cases. The recognition of MUF may justify the independent clinical consideration per individual tumor focus; as separate lesions albeit within a multifocal context. The potential clinical relevance and prognostic value of MUF remain to be further established. [ABSTRACT FROM AUTHOR]

Background: Agreement exists about most of the clinical features of erosive tooth wear, though no evidence supports their validity in diagnosing the condition. Objective: This study aimed to determine the accuracy of clinical signs for diagnosing erosive tooth wear in a young adult general population. Methods: We conducted a cross‐sectional study of dental students. In the first session, two examiners independently determined the presence of erosive tooth wear based on glazed enamel surfaces, morphological changes on non‐occlusal surfaces, flattening of convex areas, or any type of concavity. In the second session, one examiner recorded the presence of clinical signs according to the Tooth Wear Evaluation System. The diagnostic accuracy of each clinical sign, both alone and combined, was assessed by calculating their sensitivity and specificity for detecting erosive tooth wear and performing multivariate logistic regression models. Results: Of the 147 participants (78 women and 69 men; median age, 22 years) we included, 76.2% had erosive tooth wear. The single clinical signs with greatest balance between the sensitivity and specificity were 'convex areas flatten' (63% and 71%, respectively) and 'dull surface' (47% and 89%, respectively). Multivariate logistic regression revealed that 'preservation of the enamel cuff' (odds ratio, 22) and the combination of 'smooth silky shining, silky glazed appearance, and dull surface' (odds ratio, 68) had the best predictive values. Conclusions: The most accurate clinical signs for detecting early erosive tooth wear were dull surface, flattened convex areas and preservation of the enamel cuff. [ABSTRACT FROM AUTHOR]

Objective: Onset and exacerbation of autoimmune, inflammatory or steroid‐responsive conditions have been reported following the remission of Cushing syndrome, leading to challenges in distinguishing a new condition versus expected symptomatology following remission. We describe a case of a 42‐year‐old man presenting with new‐onset sarcoidosis diagnosed 12 months following the surgical cure of Cushing syndrome and synthesise existing literature reporting on de novo conditions presenting after Cushing syndrome remission. Methods: A scoping review was conducted in Medline, Epub, Ovid and PubMed. Case reports and case series detailing adult patients presenting with new‐onset conditions following Cushing syndrome remission were included. Results: In total, 1641 articles were screened, 138 full‐text studies were assessed for eligibility, and 43 studies were included, of which 84 cases (including our case) were identified. Most patients were female (85.7%), and the median reported age was 39.5 years old (IQR = 13). Thyroid diseases were the most commonly reported conditions (48.8%), followed by sarcoidosis (15.5%). Psoriasis, lymphocytic hypophysitis, idiopathic intracranial hypertension, multiple sclerosis, rheumatoid arthritis, lupus and seronegative arthritis were reported in more than one case. The median duration between Cushing remission and de novo condition diagnosis was 4.1 months (IQR = 3.75). Of those patients, 59.5% were receiving corticosteroid therapy at the time of onset. Conclusion: Our scoping review identified several cases of de novo conditions emerging following the remission of Cushing syndrome. They occurred mostly in women and within the year following remission. Clinicians should remain aware that new symptoms, particularly in the first year following the treatment of Cushing syndrome, may be manifestations of a wide range of conditions aside from adrenal insufficiency or glucocorticoid withdrawal syndrome. [ABSTRACT FROM AUTHOR]

Biallelic loss‐of‐function mutation of NUP210L, encoding a testis‐specific nucleoporin, has been reported in an infertile man whose spermatozoa show uncondensed heads and histone retention. Mice with a homozygous transgene intronic insertion in Nup210l were infertile but spermatozoa had condensed heads. Expression from this insertion allele is undefined, however, and residual NUP210L production could underlie the milder phenotype. To resolve this issue, we have created Nup210lem1Mjmm, a null allele of Nup210l, in the mouse. Nup210lem1Mjmm homozygotes show uniform mild anomalies of sperm head morphology and decreased motility, but nuclear compaction and histone removal appear unaffected. Thus, our mouse model does not support that NUP210L loss alone blocks spermatid nuclear compaction. Re‐analyzing the patient's exome data, we identified a rare, potentially pathogenic, heterozygous variant in nucleoporin gene NUP153 (p.Pro485Leu), and showed that, in mouse and human, NUP210L and NUP153 colocalize at the caudal nuclear pole in elongating spermatids and spermatozoa. Unexpectedly, in round spermatids, NUP210L and NUP153 localisation differs between mouse (nucleoplasm) and human (nuclear periphery). Our data suggest two explanations for the increased phenotypic severity associated with NUP210L loss in human compared to mouse: a genetic variant in human NUP153 (p.Pro485Leu), and inter‐species divergence in nuclear pore function in round spermatids. [ABSTRACT FROM AUTHOR]

Aim: Multidisciplinary teams (MDT) are commonly involved in the care of patients with cancer. How frequently dissent occurs within MDT has not been studied. This study aimed to determine how frequently dissent was documented in cancer MDT meetings at our institution, the reasons for this, and the opinions of MDT members on how dissent should be documented and communicated. Methods: A retrospective review of records from cancer MDT meetings at our institution from 2016 to 2020 was performed to identify cases where dissent was documented and the reasons for this. MDT members were invited to complete an online survey assessing their perceptions of how frequently dissent occurred, how comfortable they felt voicing dissenting opinions, and their opinions on how dissent should be documented and communicated. Results: Dissent was recorded in 30 of 7737 MDT case discussions (0.39%). The incidence of dissent varied from 0 to 1.2% between cancer streams. The most common reason for dissent involved the role of surgery. 27% of survey respondents felt either very or somewhat uncomfortable voicing dissenting opinions. Only 3% felt that dissent should not be documented, and none that it should not be communicated in some way, although there were wide ranging of views on how this should occur. Conclusion: Dissent was rarely documented within cancer MDT meetings at our institution, likely due to underreporting. Measuring the incidence of dissent within an MDT may be a useful performance metric. MDT should develop policies for how dissent should be managed, documented, and communicated. [ABSTRACT FROM AUTHOR]

Background: Studies aimed to assess risk factors for pelvic organ prolapse (POP) recurrence following colpocleisis with nonconclusive results. Objective: To investigate risk factors for POP recurrence following colpocleisis. Search Strategy: MEDLINE, PUBMED, Embase, Web of Science, and Cochrane databases were systematically searched. Selection Criteria: Experimental and non‐experimental studies investigating POP recurrence following colpocleisis. Data Collection and Analysis: We assessed the association between preoperative and postoperative physical examination findings, demographics and medical history, and the risk of recurrence following colpocleisis. Main Results: A total of 954 studies were identified, of which five studies comprising 2978 patients were eligible for analysis. Both preoperative and postoperative genital hiatus length were significantly longer in the recurrence group (mean difference [MD] 0.48, 95% confidence interval [CI] 0.01–0.94, P = 0.04, I2 = 0% and MD 1.15, 95% CI 0.50–1.81, P = 0.005, I2 = 0%; respectively). Preoperative total vaginal length (TVL) did not differ between groups (MD 0.05, 95% CI –0.40 to 0.50, P = 0.83, I2 = 6%), postoperative TVL was found significantly longer in the recurrence group (MD 0.07, 95% CI –0.03 to 1.38, P = 0.04, I2 = 68%). Both preoperative and postoperative perineal body did not differ between groups. Women with a previous POP surgery were more likely to experience recurrence following colpocleisis (relative risk 2.09, 95% CI 1.18–3.69, P = 0.01, I2 = 0%). Patient's age and previous hysterectomy did not affect recurrence rates. Conclusion: Wider preoperative and postoperative genital hiatus as well as longer post‐operative TVL and previous POP surgery were associated with a higher risk for recurrence following colpocleisis, highlighting the importance of appropriate patient selection and surgical technique in minimizing this risk. Synopsis: Wider genital‐hiatus and previous POP surgery were identified as risk factors for recurrent prolapse following colpocleisis, highlighting the importance of patient selection and surgical technique. [ABSTRACT FROM AUTHOR]

We examine whether cigarettes serve as substitutes for electronic nicotine delivery systems (ENDS) among ENDS users and demonstrate methodological extensions of data from a cross‐price purchase task to inform policies and interventions. During a clinical laboratory study, n = 19 exclusive ENDS users and n = 17 dual cigarette/ENDS users completed a cross‐price purchase task with cigarettes available at a fixed price while prices of own‐brand ENDS increased. We estimated cross‐price elasticity using linear models to examine substitutability. We defined five additional outcomes: nonzero cross‐price intensity (purchasing cigarettes if ENDS were free), constant null demand (not purchasing cigarettes at any ENDS price), cross‐product crossover point (first price where participants purchased more cigarettes than ENDS), dual‐demand score (percentage of prices where both products were purchased), and dual‐use break point (minimum relative price to force complete substitution). The cross‐price elasticity results indicated that cigarettes could serve as substitutes for ENDS among ENDS users on average, but this average effect masked substantial heterogeneity in profiles of demand (here, a measure of the drug's reinforcement potential). Policies and regulations that increase ENDS prices appear unlikely to steer most exclusive ENDS users toward cigarette use, as most would not purchase cigarettes at any ENDS price, but they could prompt some dual users to substitute cigarettes completely while others remain dual users. This heterogeneity in consumer responses suggests additional indices of cross‐product demand are useful to characterize the anticipated and unanticipated effects of tobacco price policies more fully. [ABSTRACT FROM AUTHOR]

Behavioral momentum theory (BMT) provides a theoretical and methodological framework for understanding how differentially maintained operant responding resists disruption. A common way to test operant resistance involves contingencies with suppressive effects, such as extinction or prefeeding. Other contingencies with known suppressive effects, such as response‐cost procedures arranged as point‐loss or increases in response force, remain untested as disruptive events within the BMT framework. In the present set of three experiments, responding of humans was maintained by point accumulation programmed according to a multiple variable‐interval (VI) VI schedule with different reinforcement rates in either of two components. Subsequently, subtracting a point following each response (Experiment 1) or increasing the force required for the response to be registered (Experiments 2 and 3 decreased response rates, but responding was less disrupted in the component associated with the higher reinforcement rate. The point‐loss contingency and increased response force similarly affected response rates by suppressing responding and human persistence, replicating previous findings with humans and nonhuman animals when other types of disruptive events (e.g., extinction and prefeeding) were investigated. The present findings moreover extend the generality of the effects of reinforcement rate on persistence, and thus BMT, extending the analysis of resistance to two well‐known manipulations used to reduce responding in the experimental analysis of behavior. [ABSTRACT FROM AUTHOR]

Drinking alcoholic beverages stimulates food intake and contributes to the passive overconsumption of dietary energy. As protein is the most satiating of all the macronutrients, increased levels in snacks taken with alcohol have the potential to minimize excess energy consumption. We hypothesized that swapping consumption from retail‐available standard protein (SP) snacks to higher protein (HP) snack foods would increase satiety and reduce acute food energy intake in social drinkers. A randomized single‐blind crossover trial with 19 healthy participants aged 19–31 years was conducted. Participants attended two separate testing sessions, where they ingested white wine (30 g alcohol) and were offered ad libitum access to either HP snacks with a protein‐fortified dip or SP snacks with a dip. There were no significant differences in mean food mass, food energy intake, or subjective appetite ratings between the high and SP snacks (all p >.05). Mean protein intake was significantly increased with HP snacks compared with standard snacks (p <.001). Plasma glucose median incremental area under the curve and mean peak were significantly higher with the SP snacks (all p <.05) but remained within the reference range. This study demonstrated that consumption of a higher amount of protein after a moderate alcohol dose does not result in a change in food mass and energy intake or promote satiety in healthy young adults. The potential for a simple swap to different snack types is unlikely to bring substantial benefits to social drinkers and reduce passive energy consumption. [ABSTRACT FROM AUTHOR]

Background: As sequencing is becoming more broadly available, virus discovery continues. Small DNA viruses contribute to up to 60% of the overall virus load in pigs. Porcine circoviruses (PCVs) are small DNA viruses with a single‐stranded circular genome. They are common in pig breeds and have not been properly addressed for their potential risk in xenotransplantation. Whereas PCV1 is non‐pathogenic in pigs, PCV2 has been associated with various disease manifestations. Recently two new circoviruses have been described, PCV3 and PCV4. While PCV4 is currently present mainly in Asia, PCV3 is widely distributed, and has been identified in commercial pigs, wild boars, and pigs generated for xenotransplantation. In one case PCV3 was transmitted by pigs to baboons via heart transplantation. PCV3 pathogenicity in pigs was controversial initially, however, the virus was found to be associated with porcine dermatitis and nephropathy syndrome (PDNS), reproductive failure, and multisystemic inflammation. Inoculation studies with PCV3 infectious clones confirmed that PCV3 is pathogenic. Most importantly, recently discovered human circoviruses (CV) are closely related to PCV3. Methods: Literature was evaluated and summarized. A dendrogram of existing circoviruses in pigs, humans, and other animal species was created and assessed at the species level. Results: We found that human circoviruses can be divided into three species, human CV1, CV2, and CV3. Human CV2 and CV3 are closest to PCV3. Conclusions: Circoviruses are ubiquitous. This communication should create awareness of PCV3 and the newly discovered human circoviruses, which may be a problem for blood transfusions and xenotransplantation in immune suppressed individuals. [ABSTRACT FROM AUTHOR]

Objective: Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant salivary gland tumor. Although multiple reviews have been published on salivary gland malignancies, it has been a decade since the last dedicated systematic review pertaining to CXPA alone was published. This study examines molecular factors in CXPA diagnosis. Data Sources: MEDLINE, CINAHL, Embase, Scopus, Web of Science (BIOSIS), Cochrane CENTRAL, Health Collection (Informit), OpenDOAR, and GreyNet International. Review Methods: Systematic review and meta‐analysis from inception to October 31, 2022 for all English language studies pertaining to "carcinoma ex pleomorphic adenoma." Predicted incidence of each biomarker was calculated with meta‐analysis. Comparison against pleomorphic adenoma (PA) and salivary duct carcinoma (SDC) when reported within the same study are performed. Risk of bias performed with JBI tool for prevalence studies. Results: Of 19151 unique studies undergoing abstract screening, 55 studies (n = 1322 patients) underwent data analysis. Biomarkers with >3 studies were p53, HER2, AR, EGFR, PLAG1, ERBB, ER, PR, HMGA2, p16, p63, a‐SMA, RAS, PTEN, PDL1, BRAF, PIK3CA, and c‐kit. Highest incidence was seen in AR, EGFR, p16, and p53. Significant differences were demonstrated compared with PA and SDC. There was high heterogeneity and overall high risk of bias within studies. Conclusion: Molecular factors are an area of interest in the diagnosis of CXPA. Our study results support examining CXPA as a discrete cohort in future targeted therapy trials. Laryngoscope, 134:1042–1053, 2024 [ABSTRACT FROM AUTHOR]

Objective: A childhood cancer diagnosis is a traumatic experience for patients and their families. However, little is known about the effect on grandparents. We aimed to investigate the negative psychosocial impact, coping strategies, and positive outcomes of grandparents of childhood cancer patients in Switzerland. Methods: We collected data using a semi‐structured interview guide and applied qualitative content analysis. Results: We conducted 20 interviews with 23 grandparents (57% female; mean age = 66.9 years; SD = 6.4; range = 57.0–82.4) of 13 affected children (69% female; mean age = 7.5 years; SD = 6.1; range = 1.0–18.9) between January 2022 and April 2023. The mean time since diagnosis was 1.0 years (SD = 0.5; range = 0.4–1.9). Grandparents were in shock and experienced strong feelings of fear and helplessness. They were particularly afraid of a relapse or late effects. The worst part for most was seeing their grandchild suffer. Many stated that their fear was always present which could lead to tension and sleep problems. To cope with these negative experiences, the grandparents used internal and external strategies, such as accepting the illness or talking to their spouse and friends. Some grandparents also reported positive outcomes, such as getting emotionally closer to family members and appreciating things that had previously been taken for granted. Conclusions: Grandparents suffer greatly when their grandchild is diagnosed with cancer. Encouragingly, most grandparents also reported coping strategies and positive outcomes despite the challenges. Promoting coping strategies and providing appropriate resources could reduce the psychological burden of grandparents and strengthen the whole family system. [ABSTRACT FROM AUTHOR]

Objective: Elective neck dissection (END) improves outcomes among clinically node‐negative patients with oral cavity squamous cell carcinoma (OCSCC). However, END is of questionable value, considering the potentially higher comorbidities and operative risks in elderly patients. Methods: A retrospective review of all patients older than 65 years of age who were treated for OCSCC at a tertiary care centre between 2005 and 2020 was conducted. Results: Fifty‐three patients underwent primary tumour resection alone, and 71 had simultaneous END. Most primary tumours were located on the mobile tongue. The patients who did not undergo END had a higher mean age (81.2 vs. 75.1 years, P < 0.00001), significantly shorter surgeries, and shorter hospitalizations. Occult cervical metastases were found in 24% of the patients who underwent END. The two groups showed no significant differences in overall survival or recurrence rates. Similar results were shown in a subpopulation analysis of patients older than 75 years. Conclusion: Foregoing END in elderly patients with no clinical evidence of neck metastases did not result in lower survival rates or higher recurrence rates. [ABSTRACT FROM AUTHOR]

Aims: The invasive pattern in HPV‐associated endocervical adenocarcinoma (HPVA) has prognostic value. Non‐destructive (pattern A) HPVA has excellent prognosis mirroring adenocarcinoma in‐situ (AIS). However, the rare occurrence of ovarian spread in these tumours suggests aggressiveness in a subset of patients with these otherwise indolent lesions. We hypothesise that AIS/pattern A HPVA with ovarian metastases are biologically different than metastatic destructively invasive HPVA. Methods and results: Samples from patients with HPVA and synchronous or metachronous metastases were retrieved and reviewed to confirm diagnosis and determine the Silva pattern in the primary lesion. For each case, normal tissue, cervical tumour and at least one metastasis underwent comprehensive sequencing using a 447‐gene panel. Pathogenic single‐nucleotide variants and segmental copy‐number alterations (CNA), tumour mutational burden and molecular signatures were evaluated and compared between primary and metastases and among invasive pattern categories. We identified 13 patients: four had AIS/pattern A primaries, while nine had pattern B/C tumours. All AIS/pattern A lesions had metastasis only to ovary; 50% of patients with ovarian involvement, regardless of invasive pattern, also had involvement of the endometrium and/or fallopian tube mucosa by HPVA. In the ovary, AIS/pattern A HPVA showed deceptive well‐differentiated glands, often with adenofibroma‐like appearance. Conversely, pattern C HPVAs consistently showed overt infiltrative features in the ovary. Sequencing confirmed the genetic relationship between primary and metastatic tumours in each case. PIK3CA alterations were identified in three of four AIS/pattern A HPVAs and three of eight pattern B/C tumours with sequenced metastases. Pattern C tumours showed a notably higher number of CNA in primary tumours compared to pattern A/B tumours. Only one metastatic AIS/pattern A HPVA had a novel pathogenic variant compared to the primary. Conversely, five of eight pattern B/C tumours with sequenced metastases developed novel pathogenic variants in the metastasis not seen in the primary. All four AIS/pattern A patients were alive and free of disease at 31, 47, 58 and 212 months after initial diagnosis. Conversely, cancer‐related death was documented in five of nine pattern B/C patients with follow‐up at 7, 20, 20, 43 and 87 months. Conclusion: Morphologically and genomically, AIS/pattern A HPVA with secondary ovarian involvement appears distinct from destructively invasive tumours. In at least a subset of these cases, ovarian spread appears to occur via trans‐Mullerian superficial extension, different from the stromal and lymphatic vascular spread typical of more aggressive tumours (pattern C). These differences may explain the indolent outcome observed in the rare subset of patients with AIS/pattern A HPVA and ovarian metastasis. Our data underscore the potential for conservative surgical management approaches to pattern A HPVA. [ABSTRACT FROM AUTHOR]

Aim: The gut microbiota has emerged as a new intervention target for sarcopenia. Prior studies in humans have focused on the association between gut microbiota and skeletal muscle quantity, while the evidence on muscle function and quality is lacking. This study aimed to identify gut microbiota genera associated with skeletal muscle function, quantity, and quality in a general population of Japanese adults. Methods: This cross‐sectional study included 164 participants aged 35–80 years, women and men recruited from urban areas of Japan. Fecal samples were collected and analyzed using 16S rRNA gene amplicon sequencing. Skeletal muscle function was measured using handgrip strength and leg extension power (LEP), while skeletal muscle mass was estimated using bioelectrical impedance analysis. Phase angle was used as a measure of skeletal muscle quality. Multivariate linear regression analysis stratified by age group was used to examine the association between the dominant genera of the gut microbiota and skeletal muscle variables. Results: A significant association was found between Bacteroides and Prevotella 9 with LEP only in the ≥60 years group. When both Bacteroides and Prevotella 9 were included in the same regression model, only Bacteroides remained consistently and significantly associated with LEP. No significant associations were observed between skeletal muscle mass, handgrip strength, and phase angle and major gut microbiota genera. Conclusions: In this study, we observed a significant positive association between Bacteroides and leg muscle function in older adults. Further studies are required to elucidate the underlying mechanisms linking Bacteroides to lower‐extremity muscle function. Geriatr Gerontol Int 2024; 24: 53–60. [ABSTRACT FROM AUTHOR]

Aim: To measure the association between cannabis use disorder (CUD) and adverse cardiovascular disease (CVD) outcomes. Design and Setting: We conducted a matched, population‐based retrospective cohort study involving five linked administrative health databases from Alberta, Canada. Participants: We identified participants with CUD diagnosis codes and matched them to participants without CUD codes by gender, year of birth and time of presentation to the health system. We included 29 764 pairs (n = 59 528 individuals in total). Measurements: CVD events were defined by at least one incident diagnostic code within the study period (1 January 2012–31 December 2019). Covariates included comorbidity, socio‐economic status, prescription medication use and health service use. Using mortality‐censored Poisson regression models, we computed survival analyses for time to incident CVD stratified by CUD status. In addition, we calculated crude and stratified risk ratios (RRs) across various covariates using the Mantel–Haenszel technique. Findings: The overall prevalence of documented CUD was 0.8%. Approximately 2.4% and 1.5% of participants in the CUD and unexposed groups experienced an incident adverse CVD event (RR = 1.57; 95% confidence interval = 1.40–1.77). CUD was significantly associated with reduced time to incident CVD event. Individuals who appeared to have greater RRs for incident CVD were those without mental health comorbidity, who had not used health‐care services in the previous 6 months, who were not on prescription medications and who did not have comorbid conditions. Conclusions: Canadian adults with cannabis use disorder appear to have an approximately 60% higher risk of experiencing incident adverse cardiovascular disease events than those without cannabis use disorder. [ABSTRACT FROM AUTHOR]

Background and Aims: Non‐alcoholic fatty liver disease (NAFLD) has been linked to type 2 diabetes (T2D), but also to hypothyroidism. Nevertheless, the relationship between thyroid function and NAFLD in diabetes is less clear. This study investigated associations between free thyroxine (fT4) or thyroid‐stimulating hormone (TSH) and NAFLD in recent‐onset diabetes. Methods: Participants with recent‐onset type 1 diabetes (T1D, n = 358), T2D (n = 596) or without diabetes (CON, n = 175) of the German Diabetes Study (GDS), a prospective longitudinal cohort study, underwent Botnia clamp tests and assessment of fT4, TSH, fatty liver index (FLI) and in a representative subcohort 1H‐magnetic resonance spectroscopy. Results: First, fT4 levels were similar between T1D and T2D (p =.55), but higher than in CON (T1D: p <.01; T2D: p <.001), while TSH concentrations were not different between all groups. Next, fT4 correlated negatively with FLI and positively with insulin sensitivity only in T2D (ß = −.110, p <.01; ß =.126, p <.05), specifically in males (ß = −.117, p <.05; ß =.162; p <.01) upon adjustments for age, sex and BMI. However, correlations between fT4 and FLI lost statistical significance after adjustment for insulin sensitivity (T2D: ß = −.021, p = 0.67; males with T2D: ß = −.033; p =.56). TSH was associated positively with FLI only in male T2D before (ß =.116, p <.05), but not after adjustments for age and BMI (ß =.052; p =.30). Conclusions: Steatosis risk correlates with lower thyroid function in T2D, which is mediated by insulin resistance and body mass, specifically in men, whereas no such relationship is present in T1D. [ABSTRACT FROM AUTHOR]

Aim: This qualitative evidence synthesis was performed to establish a conceptual model of oral health in dependent adults that defines the construct of oral health and describes its interrelationships based on dependent adults' and their caregivers' experiences and views. Methods: Six bibliographic databases were searched: MEDLINE, Embase, PsycINFO, CINAHL, OATD, and OpenGrey. Citations and reference lists were manually searched. A quality assessment of included studies was conducted independently by two reviewers using the Critical Appraisal Skills Programme (CASP) checklist. The 'best fit' framework synthesis method was applied. Data were coded against an a priori framework and data not captured by this framework were thematically analyzed. To assess the confidence of the findings from this review, the Confidence in the Evidence from Reviews of Qualitative research (GRADE‐CERQual) approach was used. Results: Twenty‐seven eligible studies were included from 6126 retrieved studies. Four themes were generated to further understand oral health in dependent adults: oral health status, oral health impact, oral care, and oral health value. Conclusion: This synthesis and conceptual model offer a better understanding of oral health in dependent adults and subsequently provide a starting point to guide establishment of person‐centred oral care interventions. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of mortality and person‐years of life lost from cancer among US men and women. Early detection has been shown to be associated with reduced lung cancer mortality. Our objective was to update the American Cancer Society (ACS) 2013 lung cancer screening (LCS) guideline for adults at high risk for lung cancer. The guideline is intended to provide guidance for screening to health care providers and their patients who are at high risk for lung cancer due to a history of smoking. The ACS Guideline Development Group (GDG) utilized a systematic review of the LCS literature commissioned for the US Preventive Services Task Force 2021 LCS recommendation update; a second systematic review of lung cancer risk associated with years since quitting smoking (YSQ); literature published since 2021; two Cancer Intervention and Surveillance Modeling Network‐validated lung cancer models to assess the benefits and harms of screening; an epidemiologic and modeling analysis examining the effect of YSQ and aging on lung cancer risk; and an updated analysis of benefit‐to‐radiation‐risk ratios from LCS and follow‐up examinations. The GDG also examined disease burden data from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Formulation of recommendations was based on the quality of the evidence and judgment (incorporating values and preferences) about the balance of benefits and harms. The GDG judged that the overall evidence was moderate and sufficient to support a strong recommendation for screening individuals who meet the eligibility criteria. LCS in men and women aged 50–80 years is associated with a reduction in lung cancer deaths across a range of study designs, and inferential evidence supports LCS for men and women older than 80 years who are in good health. The ACS recommends annual LCS with low‐dose computed tomography for asymptomatic individuals aged 50–80 years who currently smoke or formerly smoked and have a ≥20 pack‐year smoking history (strong recommendation, moderate quality of evidence). Before the decision is made to initiate LCS, individuals should engage in a shared decision‐making discussion with a qualified health professional. For individuals who formerly smoked, the number of YSQ is not an eligibility criterion to begin or to stop screening. Individuals who currently smoke should receive counseling to quit and be connected to cessation resources. Individuals with comorbid conditions that substantially limit life expectancy should not be screened. These recommendations should be considered by health care providers and adults at high risk for lung cancer in discussions about LCS. If fully implemented, these recommendations have a high likelihood of significantly reducing death and suffering from lung cancer in the United States. [ABSTRACT FROM AUTHOR]

Background and Aim: Our prior research revealed that the tumor enhancement ratio (TER) on triphasic abdominal contrast‐enhanced MDCT (CE‐MDCT) scans was a prognostic factor for patients with stages I–III colon cancer. Building upon this finding, the present study aims to investigate the proteomic changes in colon cancer patients with varying TER values. Methods: TER was analyzed on preoperative triphasic CE‐MDCT scans of 160 stages I–III colon cancer patients. The survival outcomes of those in the low‐TER and high‐TER groups were compared. Proteomic analysis on colon cancer tissues was performed by mass spectrometry (MS) and verified by immune‐histological chemistry (IHC) assays. In vivo, mouse xenograft models were employed to test the function of target proteins identified through the MS. CE‐MDCT scans were conducted on mice xenografts, and the TER values were compared. Results: Patients in the high‐TER group had a significantly worse prognosis than those in the low‐TER group. Proteomic analysis of colon cancer tissues revealed 153 differentially expressed proteins between the two groups. A correlation between TER and the abundance of α‐SMA protein in tumor tissue was observed. IHC assays further confirmed that α‐SMA protein expression was significantly increased in high‐TER colon cancer, predominantly in cancer‐associated fibroblasts (CAFs) within the cancer stroma. Moreover, CAFs promoted the growth of CRC xenografts in vivo and increased TER. Conclusions: Our study identified the distinct protein changes in colon cancer with low and high TER for the first time. The presence of CAFs may promote the growth of colon cancer and contribute to an increased TER. [ABSTRACT FROM AUTHOR]

Background and purpose: Biallelic mutation/expansion of the gene RFC1 has been described in association with a spectrum of manifestations ranging from isolated sensory neuro(no)pathy to a complex presentation as cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS). Our aim was to define the frequency and characteristics of small fiber neuropathy (SFN) in RFC1 disease at different stages. Methods: RFC1 cases were screened for SFN using the Neuropathic Pain Symptom Inventory and Composite Autonomic Symptom Score 31 questionnaires. Clinical data were retrospectively collected. If available, lower limb skin biopsy samples were evaluated for somatic epidermal and autonomic subepidermal structure innervation and compared to healthy controls (HCs). Results: Forty patients, median age at onset 54 years (interquartile range [IQR] 49–61) and disease duration 10 years (IQR 6–16), were enrolled. Mild‐to‐moderate positive symptoms (median Neuropathic Pain Symptom Inventory score 12.1/50, IQR 5.5–22.3) and relevant autonomic disturbances (median Composite Autonomic Symptom Score 31 37.0/100, IQR 17.7–44.3) were frequently reported and showed scarce correlation with disease duration. A non‐length‐dependent impairment in nociception was evident in both clinical and paraclinical investigations. An extreme somatic denervation was observed in all patients at both proximal (fibers/mm, RFC1 cases 0.0 vs. HCs 20.5, p < 0.0001) and distal sites (fibers/mm, RFC1 cases 0.0 vs. HCs 13.1, p < 0.0001); instead only a slight decrease was observed in cholinergic and adrenergic innervation of autonomic structures. Conclusions: RFC1 disease is characterized by a severe and widespread somatic SFN. Skin denervation may potentially represent the earliest feature and drive towards the suspicion of this disorder. [ABSTRACT FROM AUTHOR]

Objectives: This case series would like to highlight hypophosphatemia related to ferric carboxymaltose and its adverse clinical consequences. Background: Intravenous iron supplementation is a good alternative to oral iron replacement in iron deficiency anaemia due to its ability to correct iron deficit with minimal infusions without incurring the gastrointestinal side effects of oral iron replacement. Ferric carboxymaltose is one common formula for intravenous iron supplementation. However, an increasingly recognised adverse side‐effect of intravenous ferric carboxymaltose is hypophosphatemia. There has been increasing reports and studies highlighting hypophosphatemia related to intra‐venous iron therapy. Though initially thought to be transient and asymptomatic, recent studies have shown that persistent hypophosphatemia in iron therapy can result in debilitating disease including myopathy, fractures and osteomalacia. Methods: A retrospective analysis of all patients who had ferric carboxymaltose was performed. Results: We highlight 3 cases where hyposphatemia affected the clinical outcomes. Conclusion: With the increased use of IV iron it is important to be aware of the high potential for hypophosphatemia secondary to ferric carboxymaltose. [ABSTRACT FROM AUTHOR]

Vertebral fractures (VFs) are the hallmark of osteoporosis, being one of the most frequent types of fragility fracture and an early sign of the disease. They are associated with significant morbidity and mortality. VFs are incidentally found in one out of five imaging studies, however, more than half of the VFs are not identified nor reported in patient computed tomography (CT) scans. Our study aimed to develop a machine learning algorithm to identify VFs in abdominal/chest CT scans and evaluate its performance. We acquired two independent data sets of routine abdominal/chest CT scans of patients aged 50 years or older: a training set of 1011 scans from a non‐interventional, prospective proof‐of‐concept study at the Universitair Ziekenhuis (UZ) Brussel and a validation set of 2000 subjects from an observational cohort study at the Hospital of Holbæk. Both data sets were externally reevaluated to identify reference standard VF readings using the Genant semiquantitative (SQ) grading. Four independent models have been trained in a cross‐validation experiment using the training set and an ensemble of four models has been applied to the external validation set. The validation set contained 15.3% scans with one or more VF (SQ2‐3), whereas 663 of 24,930 evaluable vertebrae (2.7%) were fractured (SQ2‐3) as per reference standard readings. Comparison of the ensemble model with the reference standard readings in identifying subjects with one or more moderate or severe VF resulted in an area under the receiver operating characteristic curve (AUROC) of 0.88 (95% confidence interval [CI], 0.85–0.90), accuracy of 0.92 (95% CI, 0.91–0.93), kappa of 0.72 (95% CI, 0.67–0.76), sensitivity of 0.81 (95% CI, 0.76–0.85), and specificity of 0.95 (95% CI, 0.93–0.96). We demonstrated that a machine learning algorithm trained for VF detection achieved strong performance on an external validation set. It has the potential to support healthcare professionals with the early identification of VFs and prevention of future fragility fractures. © 2023 UCB S.A. and The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). [ABSTRACT FROM AUTHOR]

Human and nonhuman primate mother–infant dyads engage in face‐to‐face interactions critical for optimal infant development. In semi‐free‐ranging rhesus macaques (Macaca mulatta), maternal primiparity and infant sex influence the expression of nonverbal face‐to‐face mother–infant interactions. However, whether similar patterns of variation exist in laboratory‐housed macaques or human mothers is not well understood. Comparing both species would yield information regarding the translational validity of macaques to humans in this important social/developmental domain. In this pilot study, we first compared semi‐free‐ranging (n = 39) and laboratory‐housed (n = 20) macaques, finding that laboratory‐housed dyads, first‐time mothers, and mothers of sons engaged in higher rates of face‐to‐face interactions regardless of housing. After translating the nonhuman primate coding scheme for use in a small but diverse group of human mother–infant dyads (N = 27; 44.4% African American, 18.5% American Indian, 7.4% Asian/Asian American, and 29.6% White), we found that, like macaques, human mothers of sons engaged in more face‐to‐face interactions; however, experienced (vs. first‐time) mothers engaged in more interactions. Macaques and humans also engaged in species–specific interactions with their infants. We conclude that components of caregiver–infant nonverbal face‐to‐face interactions are translatable across human and nonhuman primate species and represent an exciting avenue for future caregiving work. [ABSTRACT FROM AUTHOR]

Mechanistic insight into ageing may empower prolonging the lifespan of humans; however, a complete understanding of this process is still lacking despite a plethora of ageing theories. In order to address this, we investigated the association of lifespan with eight phenotypic traits, that is, litter size, body mass, female and male sexual maturity, somatic mutation, heart, respiratory, and metabolic rate. In support of the somatic mutation theory, we analysed 15 mammalian species and their whole‐genome sequencing deriving somatic mutation rate, which displayed the strongest negative correlation with lifespan. All remaining phenotypic traits showed almost equivalent strong associations across this mammalian cohort, however, resting heart rate explained additional variance in lifespan. Integrating somatic mutation and resting heart rate boosted the prediction of lifespan, thus highlighting that resting heart rate may either directly influence lifespan, or represents an epiphenomenon for additional lower‐level mechanisms, for example, metabolic rate, that are associated with lifespan. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate nursing students' experiences of communication in a multilingual and multicultural clinical environment. Background: Effective communication in a healthcare setting plays a crucial role in patient care. Yet, since universities, globally, have experienced an increase in the enrolment of both local and international students in various degree programmes, student populations have become increasingly multilingual and multicultural. This study was conducted in a multilingual country where many languages are not spoken by all citizens, which results in nursing students experiencing varied outcomes. Design: A qualitative, explorative, descriptive research design was used. Methods: Sixteen nursing students enrolled in either the Bachelor of Nursing Science (Clinical, Honours) or the Diploma in Nursing Science. Data were collected by means of in‐depth, semi‐structured interviews with a sample of 16 nursing students who were selected through convenience sampling. Data were analysed using thematic analysis. Results: The study revealed four themes: aspects that complicate communication; interesting aspects about communication; the need for communication assistance; and the need for policy intervention, which is key to addressing challenges in multilingual clinical environments. [ABSTRACT FROM AUTHOR]

Steep delay and shallow probability discounting are associated with myriad problem behaviors; thus, it is important to understand factors that influence the degree of discounting. The present study evaluated the effects of economic context and reward amount on delay and probability discounting. Two hundred thirteen undergraduate psychology students completed four delay‐ or probability‐discounting tasks. Participants were exposed to hypothetical narratives involving four bank amounts ($750, $12,000, $125,000, and $2,000,000). The delayed/probabilistic amount was $3,000 for the two smaller bank amounts and $500,000 for the two larger bank amounts. The discounting tasks included five delays to, or probabilities of, receipt of the larger amount. The area under the empirical discounting function was calculated for each participant. Participants discounted delayed and uncertain outcomes more when the bank amount was smaller than the outcome (i.e., the economic context was low). Participants discounted the delayed larger amounts less than delayed smaller amounts, even when the relative economic context was the same. In contrast, probability discounting did not differ across magnitudes, which suggests that economic context may attenuate the magnitude effect in probability discounting. The results further highlight the importance of considering the economic context in delay and probability discounting. [ABSTRACT FROM AUTHOR]

Stimulus overselectivity describes strong control by one stimulus element at the expense of other equally relevant elements. Research suggests that control by underselected stimuli emerges following extinction of the overselected stimulus ("revaluation") and the emergence is larger when overselectivity is greater. We compared such revaluation effects with a control compound or condition in two experiments. Human participants chose between compound S+ and S‐ stimuli. Then, to assess control by compound‐stimulus elements, participants chose between individual elements in a testing phase without feedback. The S+ element chosen most often (the overselected element) underwent revaluation, during which choice of that element was extinguished and choice of a novel element reinforced. Thereafter, participants completed a retesting phase. Revaluation reduced choice of the overselected element. Choice of the underselected element decreased for participants with low overselectivity but increased for participants with high overselectivity. This was not the case for a control compound that did not undergo revaluation (Experiments 1 and 2) or in a control condition in which the overselected element continued to be reinforced during revaluation (Experiment 2). These findings suggest that overselectivity levels may modulate revaluation effects, and they also highlight the importance of the contingency change in postrevaluation changes in stimulus control. [ABSTRACT FROM AUTHOR]

Key Clinical Message: This study aimed to characterize the clinical features, developmental milestones, and the natural history of Pelizaeus–Merzbacher disease (PMD) associated with PLP1 gene duplications. The study examined 16 PMD Patients ranging in age from 7 to 48 years, who had a documented PLP1 gene duplication. The study examined and analyzed the medical and developmental histories of the subjects utilizing a combination of resources that included medical history questionnaires, medical record reviews, and a 31‐point functional disability scale that had been previously validated. The data extracted from the medical records and questionnaires for analysis included information related to medical and developmental histories, level of ambulation and cognition, and degree of functional disability. The summation of findings among the study population demonstrated that the presenting symptoms, developmental milestones achieved, and progression of symptoms reported are consistent with many previous studies of patients with PLP1 duplications. All patients exhibited onset within the first year of life, with nystagmus predominating as the first symptom noticed. All patients exhibited delays in both motor and language development; however, many individuals were able to meet several developmental milestones. They exhibited some degree of continued motor impairment with none having the ability to walk independently. All patients were able to complete at least some of the cognition achievements and although not all were verbal, a number were able to use communication devices to complete these tasks. A critical tool of the study was the functional disability scale which provided a major advantage in helping quantify the clinical course of PMD, and for several, we were able to gather this information at more than one point in time. These reported findings in our cohort contribute important insight into the clinical heterogeneity and potential underlying mechanisms that define the molecular pathogenesis of the disease. This is one of only a small number of natural history studies examining the clinical course of a cohort of patients with PLP1 duplications within the context of a validated functional disability scoring system. This study is unique in that it is limited to subjects with PLP1 gene duplications. This study demonstrated many commonalities to other studies that have characterized the features of PMD and other PLP1‐related disorders but also provide significant new insights into the evolving story that marks the natural history. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is a severe zoonotic mosquito‐borne disease that represents an important threat to human and animal health, with major public health and socioeconomic impacts. This disease is endemic throughout many African countries and the Arabian Peninsula. This systematic review with meta‐analysis was conducted to determine the RVF prevalence in humans, mosquitoes and other animal species in Africa. The review also provides contemporary data on RVF case fatality rate (CFR) in humans. In this systematic review with meta‐analysis, a comprehensive literature search was conducted on the PubMed, Embase, Web of Science and Global Index Medicus databases from January 2000 to June 2022 to identify relevant studies. Pooled CFR and prevalence estimates were calculated using the random‐effects model. Subgroup analysis and sensitivity analysis were performed, and the I2‐statistic was used to investigate a potential source of heterogeneity. A total of 205 articles were included in the final analysis. The overall RVF CFR in humans was found to be 27.5% [95% CI = 8.0–52.5]. The overall pooled prevalence was 7.8% [95% CI = 6.2–9.6] in humans and 9.3% [95% CI = 8.1–10.6] in animals, respectively. The RVF prevalence in individual mosquitoes ranged from 0.0% to 25%. Subgroup analysis showed substantial heterogeneity with respect to geographical regions and human categories. The study shows that there is a correspondingly similar prevalence of RVF in human and animals; however, human CFR is much higher than the observed prevalence. The lack of a surveillance programme and the fact that this virus has subclinical circulation in animals and humans could explain these observations. The implementation of a One Health approach for RVF surveillance and control would be of great interest for human and animal health. [ABSTRACT FROM AUTHOR]

Background: Accurately estimating baseline kidney function is essential for diagnosing acute kidney injury (AKI) in patients with chronic kidney disease (CKD). We developed and evaluated novel equations to estimate baseline creatinine in patients with AKI on CKD. Methods: We retrospectively analysed 5649 adults with AKI out of 11 254 CKD patients, dividing them evenly into derivation and validation groups. Using quantiles regression, we created equations to estimate baseline creatinine, considering historical creatinine values, months since measurement, age, and sex from the derivation dataset. We assessed performance against back‐estimation equations and unadjusted historical creatinine values using the validation dataset. Results: The optimal equation adjusted the most recent creatinine value for time since measurement and sex. Estimates closely matched the actual baseline at AKI onset, with median (95% confidence interval) differences of just 0.9% (−0.8% to 2.1%) and 0.6% (−1.6% to 3.9%) when the most recent value was within 6 months to 30 days and 2 years to 6 months before AKI onset, respectively. The equation improved AKI event reclassification by an additional 2.5% (2.0% to 3.0%) compared to the unadjusted most recent creatinine value and 7.3% (6.2% to 8.4%) compared to the CKD‐EPI 2021 back‐estimation equation. Conclusion: Creatinine levels drift in patients with CKD, causing false positives in AKI detection without adjustment. Our novel equation adjusts the most recent creatinine value for drift over time. It provides more accurate baseline creatinine estimation in patients with suspected AKI on CKD, which reduces false‐positive AKI detection, improving patient care and management. Summary at a Glance: Chronic kidney disease (CKD) increases patients' risk of acute kidney injury (AKI). Estimated baseline creatinine is required to diagnose AKI. However, CKD complicates estimation of baseline creatinine levels. Kidney function declines in CKD, leading to a rise in creatinine levels, which means patients without recent creatinine values may be wrongly diagnosed with AKI. In this study of 5649 adults with AKI on CKD, using conventional approaches for comparison, we developed and validated new equations with better accuracy and reclassification performance to estimate baseline creatinine in patients with AKI on CKD. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer (PCa) is a clinically heterogeneous disease. The creation of an expression‐based subtyping model based on prostate‐specific biological processes was sought. Methods: Unsupervised machine learning of gene expression profiles from prospectively collected primary prostate tumors (training, n = 32,000; evaluation, n = 68,547) was used to create a prostate subtyping classifier (PSC) based on basal versus luminal cell expression patterns and other gene signatures relevant to PCa biology. Subtype molecular pathways and clinical characteristics were explored in five other clinical cohorts. Results: Clustering derived four subtypes: luminal differentiated (LD), luminal proliferating (LP), basal immune (BI), and basal neuroendocrine (BN). LP and LD tumors both had higher androgen receptor activity. LP tumors also had a higher expression of cell proliferation genes, MYC activity, and characteristics of homologous recombination deficiency. BI tumors possessed significant interferon γactivity and immune infiltration on immunohistochemistry. BN tumors were characterized by lower androgen receptor activity expression, lower immune infiltration, and enrichment with neuroendocrine expression patterns. Patients with LD tumors had less aggressive tumor characteristics and the longest time to metastasis after surgery. Only patients with BI tumors derived benefit from radiotherapy after surgery in terms of time to metastasis (hazard ratio [HR], 0.09; 95% CI, 0.01–0.71; n = 855). In a phase 3 trial that randomized patients with metastatic PCa to androgen deprivation with or without docetaxel (n = 108), only patients with LP tumors derived survival benefit from docetaxel (HR, 0.21; 95% CI, 0.09–0.51). Conclusions: With the use of expression profiles from over 100,000 tumors, a PSC was developed that identified four subtypes with distinct biological and clinical features. Plain language summary: Prostate cancer can behave in an indolent or aggressive manner and vary in how it responds to certain treatments.To differentiate prostate cancer on the basis of biological features, we developed a novel RNA signature by using data from over 100,000 prostate tumors—the largest data set of its kind.This signature can inform patients and physicians on tumor aggressiveness and susceptibilities to treatments to help personalize cancer management. Data from over 100,000 prostate tumors and multiple cohorts were used to create and validate an expression‐based signature that can subtype prostate cancer on the basis of biological features and treatment susceptibilities. [ABSTRACT FROM AUTHOR]

Background: Narrow diameter implants (NDIs) are used in cases of limited mesio‐distal space, or if the alveolar ridge does not allow placement of a standard diameter implant. Purpose: The aim of this prospective case series study is to present the 5‐year clinical‐, radiological‐, and patient‐reported outcome measures (PROMs) of patients with partial edentulism in the anterior area of the jaws requiring the placement of two narrow diameter implants to support a 3‐ or 4‐unit fixed partial denture (FPD). Materials and Methods: Thirty partially edentulous patients missing 3 or 4 adjacent teeth in the anterior area of the jaws were included in the study. Two titanium–zirconium tissue‐level NDIs were placed in each patient in healed anterior sites (60 implants). A conventional loading protocol was performed to provide a FPD. Implant survival, success, marginal bone‐level changes (MBL), clinical parameters, buccal bone stability with CBCT, adverse events and PROMs were recorded. Results: The survival and success rates for the implants were 100%. The mean MBL (±SD) after prosthesis delivery, and 5‐year follow‐up (mean 58.8 months; range: 36–60) was 0.12 ± 0.22 and 0.52 ± 0.46 mm, respectively. Decementation and screw loosening were the most frequent prosthetic complications, yielding a prosthetic survival and success rates of 100% and 80%, respectively. Patient satisfaction was high with a mean (±SD) score of 89.6 ± 15.1. Conclusions: The use of tissue‐level titanium–zirconium NDIs supporting splinted multi‐unit FPDs in the anterior area seems to be a safe and predictable treatment option after a 5‐year follow‐up period. [ABSTRACT FROM AUTHOR]