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Objectives: The measurement of fasting glucose is a common practice for lowering the risk of hyperglycemia before an oral glucose tolerance test (OGTT). In this study we analyze advantages and limitations of near-patient measurement of capillary fasting glucose with a portable glucometer or blood sampling and measurement of plasma glucose with laboratory instrumentation., Methods: The final study population consisted of 241 subjects (mean age: 36 ± 8 years; 97.9 % pregnant women) referred to our local phlebotomy center for an OGTT. Fasting glucose was measured in capillary blood using a near-patient glucometer (glucometer-based strategy) and in plasma with laboratory instrumentation using the hexokinase reference assay (laboratory-based strategy)., Results: The mean turnaround time from sample collection to obtaining the glucose value was longer with the laboratory-based strategy (32 min 8 vs. 8 s). The imprecision of the glucometer was higher than that of the laboratory assay (3.4 vs. 0.8 %). A negative bias of -3.3 % in fasting glucose was found with the glucometer compared to the laboratory measurement. The diagnostic accuracy, sensitivity and specificity of the glucometer for detecting fasting glucose values ≥7.0 mmol/L were 99.2 , 50.0 and 100.0 % compared to the laboratory assay. The glucometer-based strategy had an incremental cost of 0.17€ per patient compared to the laboratory-based strategy., Conclusions: Screening fasting glucose in capillary blood with a near-patient glucometer instead of measuring fasting plasma glucose with laboratory instrumentation allows faster patient management in the phlebotomy center but is associated with higher imprecision, inaccuracy, costs and avoidable finger pricks., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal events including an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord 1,2 . This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptaken glutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Autologous fat grafting is a widely used technique in plastic and reconstructive surgery for soft tissue augmentation. Despite its advantages, the primary limitation is the unpredictable retention rate of transplanted fat. Recent studies suggest that botulinum toxin type A (BTX-A) can enhance fat graft survival by promoting angiogenesis and muscle paralysis., Aims: This review explores the potential of BTX-A as an adjuvant in autologous fat grafting, providing insights into its mechanisms, benefits, and the need for further clinical validation., Patients/methods: A literature review was conducted using PubMed, Web of Science, MEDLINE, and Embase. Keywords related to BTX-A, fat grafting, fat graft survival, and angiogenesis were used. Comparative studies reporting histological changes following BTX-A application in fat grafting were included. Exclusion criteria involved case reports with fewer than three animals, reviews, and letters., Results: The initial search yielded 108 articles, with seven experimental studies meeting the criteria. These studies demonstrated that BTX-A enhances fat graft retention by promoting vascularization and adipose-derived stem cell differentiation. However, these results are mainly based on small animal models., Conclusions: While BTX-A shows promise in improving autologous fat grafting outcomes, its efficacy and safety in humans need validation through large-scale clinical trials. Translating these preclinical findings into human trials is crucial to establish standardized protocols and optimize clinical outcomes. Future research should focus on optimizing dosage and injection sites, conducting long-term follow-up studies, and performing multicenter trials to verify the findings., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Hypertension is a major risk factor for both stroke and cognitive impairment, but it is unclear whether it may specifically affect post-stroke cognitive impairment. We assessed the effect of hypertension and/or stroke on brain injury, cognitive outcome, and the brain transcriptomic profile. C57BL/6J mice (n = 117; 3-5 mo.) received s.c. infusion of either saline or angiotensin II followed by sham surgery or photothrombotic stroke targeting the prefrontal cortex seven days later. Cognitive function was assessed with the Barnes maze and RNA sequencing was used to quantify transcriptomic changes in the brain. Angiotensin II treatment produced spontaneous hemorrhaging after stroke. In the Barnes maze, hypertensive mice that received stroke surgery had an increased escape latency compared to other groups (day 3: hypertensive + stroke = 166.6 ± 6.0 s vs. hypertensive + sham = 122.8 ± 13.8 s vs. normotensive + stroke = 139.9 ± 10.1 s vs. normotensive + sham = 101.9 ± 16.7 s), consistent with impaired cognition. RNA sequencing revealed >1500 differentially expressed genes related to neuroinflammation in hypertensive + stroke vs. normotensive + stroke, which included genes associated with apoptosis, microRNAs, autophagy, anti-cognitive biomarkers and Wnt signaling. Overall, we show that the combination of hypertension and stroke resulted in greater learning impairment and brain injury., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The Menstrual Distress Questionnaire (MDQ) is a commonly used questionnaire that assesses various symptoms and distress associated with the menstrual cycle in women. However, the questionnaire has not been completely translated into Chinese with rigorous reliability and validity testing., Methods: This study translated the Menstrual Distress Questionnaire Form Cycle (MDQC) from English into Chinese: MDQCC in two stages. First, it was translated forward and backward using Jones' model; second, to test the validity and reliability, 210 Chinese-speaking women were recruited through online announcements and posters posted between June 2019 and May 2020. Expert validity, construct validity, convergent validity, and factorial validity were determined using content validity index (CVI), intraclass correlation coefficient (ICC), composite reliability (CR), and exploratory factor analysis, respectively. For concurrent criterion validity, MDQCC score was compared with three existing pain scales. Reliability was evaluated using internal consistency across items and two-week test-retest reliability over time., Results: The CVI for content validity was .92. Item-CVI for expert validities among the 46 items ranged from .50 - 1; scale-CVI for the eight subscales, from .87 - 1; ICC, from .650 - .897; and CRs, from .303 - .881. Pearson correlation coefficients between MDQCC and short-form McGill pain questionnaire, present pain intensity, and visual analog scale scores were .640, .519, and .575, respectively. Cronbach's α for internal consistency was satisfactory (.932). ICC for test-retest reliability was .852 for the entire MDQCC., Conclusion: MDQCC was valid and reliable for Mandarin Chinese-speaking women. It can be used to evaluate female psychiatric symptoms related to the menstrual cycle in future work.

Rice false smut disease, caused by the fungal pathogen Ustilaginoidea virens, significantly restricts both the production and quality of rice grains. However, the molecular mechanism underlying rice resistance against U. virens remain largely elusive. Transcriptome analysis of rice panicles infected with U. virens revealing the crucial role of genes involved in sakuranetin biosynthesis in conferring resistance to the pathogen. In vitro assays demonstrated that sakuranetin was most effective at inhibiting mycelial growth, spore germination, and host infection by U. virens. The expression of OsNOMT, the key enzyme in sakuranetin biosynthesis, is directly regulated by the transcription factor OsWRKY67. Furthermore, OsMPK6, a mitogen-activated protein kinase, interacts with and phosphorylates OsWRKY67, thereby modulating sakuranetin biosynthesis and resistance to U. virens. Moreover, the exogenous application of synthetic sakuranetin significantly reduces U. virens infection. Our findings reveal that the OsMPK6-OsWRKY67-OsNOMT signaling cascade plays a pivotal role in rice resistance to U. virens by regulating sakuranetin biosynthesis., (© 2024 The Author(s). New Phytologist © 2024 New Phytologist Foundation.)

The mucociliary clearance (MC) system is a vital host defense against infection in the lung. MC system function is dependent on ciliary density, structure, and function and airway surface liquid (ASL) composition and hydration. Animal and human studies indicate that MC rate decreases with age which may contribute to the increased rates of pulmonary infection experienced by older people. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene encodes an anion channel on epithelial surfaces that plays a key role in maintaining ASL hydration. Failure or dysfunction of CFTR could result in the dehydration of airway mucus, depressing MC. Here we use two available databases including bulk (GTEx) and single-cell (CELLxGENE) sequencing data from the lung to determine if CFTR expression decreases with age. Bulk expression data and single-cell expression data from goblet, club, and respiratory basal cells all demonstrated patterns of decreasing CFTR expression with age. Ciliated airway cells did not. Secretory cells (including club and goblet cells) and basal cells are the largest source of CFTR expression in the airway. This indicates that changes in CFTR expression and ASL dehydration may contribute to the decreasing MC associated with aging., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Purpose: Analysis of circulating tumor DNA (ctDNA) may enable early identification of patients likely to relapse, presenting an opportunity for early interventions and improved outcomes. Tumor-naïve plasma-only approaches for molecular residual disease (MRD) assessment accelerate turnaround time, enabling rapid treatment decisions and ongoing surveillance., Experimental Design: Plasma samples were obtained from 80 study participants with stage II or III colorectal cancer (CRC) selected from CIRCULATE-Japan GALAXY. MRD status was assessed using a tumor-naïve ctDNA assay (xM) that integrates methylation and genomic variant data, delivering a binary call. MRD was assessed at 4 weeks post-surgery (landmark timepoint (LMT)) using methylation and genomic variant data and longitudinally (median 22.1 months) using only methylation data., Results: At LMT, 69/80 study participants were evaluable (36 recurrent; 33 non-recurrent). Of recurrent study participants, 22/36 had detectable ctDNA (MRD+) at LMT and 29/33 non-recurrent study participants had undetectable ctDNA (MRD-), yielding clinical sensitivity of 61.1% and specificity of 87.9%. Additionally, 74 study participants were evaluable for longitudinal performance with a clinical sensitivity of 83.3% and specificity of 89.5%. Median lead time from first MRD+ result to recurrence was 4.77 months overall, and 5.30 months for study participants with no adjuvant treatment. At 12 weeks post-surgery, MRD status strongly correlated with disease-free survival (DFS) [adj. HR 9.69], outperforming carcinoembryonic antigen (CEA) correlation [HR 2.13]., Conclusions: This tumor-naïve MRD assay demonstrated clinically meaningful performance at LMT and longitudinally, accurately predicting clinical recurrence. MRD status was a stronger prognostic biomarker to DFS compared to standard of care CEA.

Objectives: Four endemic human coronaviruses (HCoVs), HCoV-229E, HCoV-NL63, HCoV-HKU1, and HCoV-OC43, infect humans during childhood and cause the common cold. COVID-19 caused by SARS-CoV-2 leads to mild symptoms in children, possibly owing to the protection conferred by immunity developed during a previous HCoV infection. This study analyzed the seroreactivity of four endemic HCoVs and SARS-CoV-2 in children and adults., Methods: A total of 747 serum samples (from individuals aged 6 months to 69 years) were collected from 2015 to 2019 before the COVID-19 pandemic in Japan. The samples were tested for immunoglobulin G antibodies against the four endemic HCoVs and SARS-CoV-2 wild-type spike ectodomain proteins using enzyme-linked immunosorbent assay., Results: The seroprevalence of endemic HCoVs (except HCoV-229E) showed 90% positivity by 3-4 years old, whereas HCoV-229E seroprevalence was observed at 8 years old. Approximately 35% of the samples showed reactivity to SARS-CoV-2 and did not change with age. However, the children's group presented higher antibody levels than the adult group. The sample reactivity against SARS-CoV-2 did not confirm neutralization capability., Conclusions: The reactive samples against SARS-CoV-2 showed varying antibody levels among different age groups. These findings may contribute to a deeper understanding of the clinical symptoms of COVID-19 and coronavirus diseases., Competing Interests: The authors have no competing interests to declare., (© 2024 The Author(s).)

Background: Botulism is a rare and life-threatening disease caused by the potent botulinum neurotoxin (BoNT), which can be produced by Clostridium botulinum (C. botulinum) and related bacteria. Clinical manifestations, which include a symmetrical, descending muscular paralysis, generalized hypotonia, and potentially respiratory failure, are non-specific and diagnosis is challenging, especially when anamnesis does not reveal any typical risk factor, like honey consumption., Case Presentation: We present what is, to the best of our knowledge, the first documented case of infant botulism (IB) in Sicily and discuss its peculiarities and the challenges faced in the diagnostic-therapeutic process. The infant was exclusively breastfed and no history of consumption of possibly contaminated foods, like honey, was found. The signs observed at presentation included poor suction, hypotonia, and hyporeactivity. A detailed anamnesis motivated the suspicion of botulism, due to the occurrence of constipation and exposure to dust from home renovation works during the days before the onset of symptoms. The botulinum antitoxin was administered and the diagnosis was confirmed through fecal examination, detecting toxin-producing C. botulinum., Conclusion: IB should be considered in every infant with rapidly progressing hypotonia and a history of constipation. However rarely, transmission could occur through inhalation of dust particles containing the toxin, therefore it is important to explore all possible sources of exposure. In the case described, timely diagnosis and treatment determined the successful outcome, which highlights the importance of early intervention in managing IB., (© 2024. The Author(s).)

Objective: Overcrowding scores have been studied extensively in adult emergency departments (EDs), but few studies have determined utility in the pediatric setting. The objective of this study was to determine the association between a modified National Emergency Department Overcrowding Score (mNEDOCS) and established ED metrics in a large academic tertiary care pediatric ED., Methods: NEDOCS was modified to increase applicability in the pediatric setting by including the number of patients in resuscitation rooms instead of a number of patients on ventilators. Patient characteristics, ED disposition, ED length of stay (LOS), rate of left without being seen (LWBS), hospital LOS (HLOS), ED returns within 72 hours, and mNEDOCS were acquired retrospectively for every ED encounter in 2016-2019 using the electronic health record. Descriptive statistics, Spearman correlation, and multivariate analyses were calculated to evaluate the association between specific ED metrics and mNEDOCS., Results: Modified NEDOCS positively correlated with ED LOS, LWBS, and rate of 72-hour return visits. A negative correlation was found between mNEDOCS and HLOS. When controlling for select covariates, the odds of LWBS doubled with each increase in mNEDOCS category (odds ratio, 2.03; 95% confidence interval [CI], 2.00-2.06), ED LOS was associated with an increase of 27 minutes as mNEDOCS category increased ( β = 26.80; 95% CI, 26.44-27.16), and the odds of 72-hour return visits increased by 6% when mNEDOCS increased by one category (odds ratio, 1.06; 95% CI, 1.05-1.07). Hospital LOS was associated with a 100-minute decrease per increase in mNEDOCS category ( β = -99.85; 95% CI, -180.68 to -18.48) when controlling for covariates., Conclusion: Modified NEDOCS is positively associated with ED LOS, LWBS, and 72-hour return visits, consistent with adult data. Further investigation is needed to elucidate the association between mNEDOCS and HLOS. This study illustrates the utility of mNEDOCS as a measure of overcrowding in a pediatric ED., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Paediatric immune thrombocytopenia treatment was revolutionized with the advent of the thrombopoietin mimetics romiplostim and eltrombopag. For eltrombopag, dosing recommendations have been based on patients' ages (with dose reductions for those with hepatic impairment and for some of East Asian ethnicity) and titrated based on platelet counts and adverse drug reactions. However, it is clear that identical eltrombopag dosing for paediatric patients can result in variable side effects and platelet counts, raising the question as to whether variable eltrombopag plasma concentrations are responsible for these differing drug responses. Commentary on: Dong et al. Exploratory study on the individualized application of eltrombopag in paediatric immune thrombocytopenia guided by therapeutic drug monitoring. Br J Haematol 2024; 205:1930-1937., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: Intestinal ultrasound (IUS) is a noninvasive tool in ulcerative colitis (UC), but scoring systems have mostly been developed for adults, Crohn's disease, and flaring UC. Our aim was to evaluate the performance of bowel wall thickness (BWT) and four IUS scores in pediatric patients with newly diagnosed UC., Methods: Patients <18 years old with suspected UC were prospectively enrolled. Baseline IUS was done, and ulcerative colitis intestinal ultrasound score (UC-IUS), Milan criteria, simple pediatric activity ultrasound score (SPAUSS), and Civatelli Index were calculated. Mayo endoscopic segment subscore, pediatric ulcerative colitis activity index (PUCAI), and biomarkers were correlated with IUS using nonparametric and receiver operating characteristic analyses., Results: Fifty-two patients (56% male, median age 13.9 years, interquartile range [IQR] 11.2-16.3) with 206 colon segments were included. Patients who needed hospitalization (n = 27/52) had significantly worse IUS (BWT and all scores) compared to those not hospitalized. For all patients, IUS scores and BWT significantly correlated with baseline endoscopic, clinical, and biochemical disease activity (p = 0.32-0.67, p < 0.05). BWT (τ b  = 0.53), UC-IUS (τ b  = 0.55), and Milan (τ b  = 0.52) had the strongest endoscopic correlations. For differentiating between endoscopic disease severity, BWT, UC-IUS, and Milan, had the highest areas under the curve (0.89-0.93). Using BWT alone, a thinner cut-off had improved sensitivity while maintaining high specificity: ≥2.5 mm for moderate/severe endoscopic inflammation (sensitivity 66%; specificity 94%) and ≥3.5 mm for severe endoscopic inflammation (sensitivity 92%; specificity 86%)., Conclusions: BWT and all four IUS scores correlated well with endoscopic, clinical, and biochemical disease activity, and was another useful marker of severity in identifying patients needing hospitalization. Pediatric patients needed a thinner BWT cut-off, which should be accounted for when developing pediatric-specific scores. BWT alone may be just as clinically useful as composite US scores., (© 2024 The Author(s). Journal of Pediatric Gastroenterology and Nutrition published by Wiley Periodicals LLC on behalf of European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)

Background: Prospective multicenter data on the treatment and outcomes of children with cerebral sinovenous thrombosis (CSVT) are limited. We aimed to describe the clinical characteristics, treatment strategies, and outcomes of patients with a first-episode of provoked acute CSVT enrolled in the Kids-DOTT trial and compare these features with those of participants with non-CSVT venous thromboembolism (VTE)., Methods: This was a subgroup analysis from the Kids-DOTT trial, a multinational randomized clinical trial on duration of anticoagulation for provoked acute VTE in patients younger than 21 years. Patient and thrombus characteristics, treatments, and outcomes of patients diagnosed with CSVT were compared with those of patients with non-CSVT VTE., Results: CSVT was diagnosed in 75 of the 532 (14%), 25 of whom received 6 weeks of anticoagulant treatment and 50 received 3 or more months. When compared with non-CSVT VTE, CSVT was more likely to occur in neonates and young children, associated with infection in general and acute head/neck infection in particular, and less likely to be related to central venous catheter. No patient in either group developed symptomatic recurrent VTE or clinically relevant bleeding, and there was no significant difference in rates of complete thrombus resolution between the 2 treatment durations., Conclusion: CSVT is most common in neonates and young children and those with acute head and neck infections. A 6-week anticoagulation treatment course appears to be safe (no clinically relevant bleeding) and effective (no difference in symptomatic recurrent VTE) for provoked acute pediatric CSVT. Nevertheless, given the nature of a subpopulation analysis, these findings should be interpreted with caution., (© 2024 The Authors.)

The -N + (CH 3 ) 3 residue is present in acetylcholine (ACh) and in many of its analogues which are used as selective ACh agonist or antagonists for human therapy. The X-ray structures of four ACh derivatives show the presence of short and linear contacts between the C atoms of -N + (CH 3 ) 3 groups and lone pair possessing atoms. These contacts can be rationalized as tetrel bonds (TtBs) thanks to their geometric features. Interrogation of the Protein Data Bank suggests that similar -N + -C⋅⋅⋅nucleophile contacts affect the details of the binding of ACh and its derivatives to proteins. Quantum theory of atoms in molecules, noncovalent interaction plot, and natural bond orbital analyses consistently confirm that the -N + -C⋅⋅⋅nucleophile contacts observed in small molecule crystals and in substrate/protein complexes are attractive in nature and can be rationalized as TtBs. TtBs involving methyl groups of the -N + (CH 3 ) 3 moiety can be proposed as a new item in the palette of interactions allowing the compounds containing this pharmacophoric unit to bind to their target protein and/or to express their biological/pharmacological properties., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Few studies have investigated the associations between phthalate exposure and kidney function indicators in adults by simultaneously performing covariate-adjusted creatinine standardization, cumulative risk assessment, and mixture analysis. Thus, we applied these methods simultaneously to investigate the aforementioned associations in an adult population. This cross-sectional study analyzed data (N = 839) from a community-based arm of the Taiwan Biobank. The levels of 10 urinary phthalate metabolites were measured and calculated as the sum of the molar concentrations of the dibutyl phthalate metabolite (ΣDBPm) and di(2-ethylhexyl) phthalate (DEHP) metabolite (ΣDEHPm). The hazard index (HI) and daily intake (DI) were estimated by measuring the urinary levels of the phthalate metabolite. Kidney function biomarkers were assessed by measuring the following: blood urea nitrogen (BUN), uric acid, the albumin-to-creatinine ratio (ACR), and the estimated glomerular filtration rate (eGFR). Generalized linear models were implemented to examine the associations between exposure to individual phthalates, HI scores, and kidney function biomarkers. We also employed Bayesian kernel machine regression (BKMR) to analyze the relationships between exposure to various combinations of phthalates and kidney function. ΣDEHPm levels were significantly and positively associated with BUN and ACR levels, and ΣDBPm levels were positively associated with ACR levels. In addition, eGFR was negatively associated with ΣDBPm and ΣDEHPm levels. In the BKMR model, a mixture of 10 phthalate metabolites was significantly associated with BUN, uric acid, ACR, and eGFR results. Higher DI DEHP and higher DI DnBP values were significantly associated with lower eGFRs and higher ACRs, respectively. Higher DI DiBP and DI DEP values were significantly associated with higher uric acid levels. A higher HI was significantly associated with lower eGFRs and higher ACRs. Our results suggest that exposure to environmental phthalates is associated with impaired kidney function in Taiwanese adults., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This is an observational case report to detail a novel case of scleroderma renal crisis presenting as bilateral exudative retinal detachments in a patient with newly diagnosed systemic sclerosis. An otherwise healthy 58-year-old female presented primarily with vision complaints and was found to have malignant hypertension (230/120 mm Hg) and bilateral exudative retinal detachment on dilated fundus examination and macular OCT scan. Further history revealed sclerodactyly, mild dysphagia, and dyspnea. She was diagnosed with diffuse systemic sclerosis and Sjogren's syndrome complicated by an episode of scleroderma renal crisis based on initial medical workup. She was admitted to intensive care for management of refractory hypertension with IV antihypertensive therapy. Three months after treatment, her visual symptoms and ocular findings resolved. The presence of exudative retinal detachment among other signs of hypertensive retinopathy warrants thorough systemic screening for underlying causes of malignant hypertension, including systemic sclerosis. Treatment of the underlying disease with urgent antihypertensive therapy resolved the exudative retinal detachments and restored vision in the case of a scleroderma renal crisis., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Solitary fibrous tumor of the liver (SFTL) is an exceptionally rare mesenchymal tumor, with only 117 cases reported in the literature. While most SFTs are benign, some exhibit malignant behavior, including local recurrence and metastasis. This report presents two cases of SFTL with systemic metastases, both involving prior intracranial tumors. The first case, a 52-year-old woman, discovered a liver mass incidentally during a routine physical exam. Subsequent investigations revealed potential bone metastasis, and biopsy confirmed SFT. She received two TACE procedures, anlotinib targeted therapy, and radiotherapy for the iliac bone lesion, resulting in stable disease with reduction in lesion size. The second case, a 46-year-old man, presented with multiple liver, pelvic, and lung lesions following pelvic tumor resection, with pathology confirming SFT. He was treated with long-term anlotinib therapy, CyberKnife for hepatic, lung, and pelvic lesions, and radiofrequency ablation for hepatic lesions. Postoperative recovery was uneventful, with no tumor progression on follow-up. SFTL presents with atypical clinical and imaging features, and diagnosis requires pathological and genetic confirmation. Radical resection is preferred for solitary tumors, while comprehensive treatment, including surgery and long-term follow-up, is essential for cases with recurrence or metastasis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wei, Lo, Gao, Zhu, Sun and Li.)

Objective: Aromatase inhibitors (AIs) are a class of medications used for adjuvant treatment of breast cancer. Recent case reports suggest that AIs may be associated with various ocular adverse events (AEs). This study evaluates the risk of ocular AEs in patients who take AIs., Method: Disproportionality analysis was performed using data from the U.S. Food and Drug Administration's Adverse Events Reporting System database from 2004 to 2022. All cases of vitreomacular traction, macular edema, retinal deposits, retinal artery occlusion, macular hole, retinal hemorrhage, uveitis, retinal tear, retinal detachment, dry eye disease, blepharitis, and optic neuropathy were searched for the 3 AIs anastrozole, letrozole, and exemestane. A search also was performed on trastuzumab as a control. Reported odds ratios (RORs) and corresponding 95% CIs were computed., Results: We identified 322 ocular AEs of interest for the 3 AIs and 55 for trastuzumab. Anastrozole had the most AEs (n = 163) and was found to have strong associations with vitreomacular traction (ROR = 665; 95% CI, 352-1255), macular edema (ROR = 37; 95% CI, 25-54), retinal deposits (ROR = 11; 95% CI, 2-77), and uveitis (ROR = 6; 95% CI, 4-9). Letrozole had strong associations with retinal deposits (ROR = 8, 95% CI, 1-57) and retinal artery occlusion (ROR = 6; 95% CI, 3-11). Exemestane had a strong association with macular holes (ROR = 10; 95% CI, 3-30)., Conclusion: Disproportionality analysis revealed an increased risk of ocular AEs with each of the AIs. This study calls for clinicians, especially oncologists and ophthalmologists, to be vigilant in patients who are on AI therapy, allowing them to provide prompt interventions to mitigate further ocular morbidities., (Copyright © 2023. Published by Elsevier Inc.)

Theory and research suggest that threats aroused by a given crisis lead to conspiracy beliefs. Although crises involve the arise of multiple threats (e.g., economic, safety, etc.) diversely affecting various needs and outcomes (i.e., cognition, emotion and behaviour), no research has yet focused on specific relations that different threats may have with the endorsement of conspiracy beliefs. In this study, we distinguished between health and economic threats aroused by the COVID-19 pandemic, and we tested their associations with conspiracy beliefs. Findings from two correlational studies conducted in Italy and Argentina showed that while COVID-19's economic threat was positively and consistently related to conspiracy beliefs, the relationship between COVID-19's health threat and conspiracy beliefs was negative and significant in the Italian sample and non-significant in the Argentinian sample. Results are discussed within the context of the effects of multiple threats elicited by crises on conspiracy beliefs., (© 2024 International Union of Psychological Science.)

Introduction: Caring for the dying can generate anxiety and emotional distress, particularly in nursing students, and perceived competence could play a crucial role in enabling nurses to perform their duties with greater confidence. Unfortunately, few studies describe the relationship between students' nursing attitudes and perceived self-efficacy in palliative care (PC). To overcome this gap, this survey aimed to assess the attitudes towards dying patients and the perceived competence of nursing students in palliative care at different universities in the south of Italy. Methods: A cross-sectional study was conducted from September 2022 to March 2023 involving nursing students from the three major Sicilian universities (Italy). The study included a survey investigating socio-demographic characteristics, palliative care training, knowledge about pain management, and previous experience with dying. Moreover, the Professional Competence of the Core Curriculum in Palliative Care Nursing (CCPCN) questionnaire and the Frommelt Attitudes Toward Care of the Dying-B Italian version (FATCOD-B-I) assessed competencies and emotional attitudes. Results: A total of 1913 nursing students were recruited, of which 71.3% were females, and 53.9% were in the age range of 18 to 21 years. In the multivariable analysis, practical PC training was a substantial factor in enhancing competencies (Adj-OR 2.78 [95% CI = 2.12-3.65]). Male students had higher competence odds (Adj-OR 1.38 [95% CI = 1.14-1.66]), and perceived knowledge strongly correlated with self-assessed competence. Advancement in academic years also positively influenced competence self-assessment (Adj-OR 1.98 [95% CI = 1.75-2.24]). Regarding emotional attitudes, a per-quartile increase in competence score was found to improve the attitude score (Adj-OR 1.24 [95% CI = 1.13-1.35]). Conclusions: Nursing students gain valuable experience during clinical experience. PC training and perceived knowledge of PC significantly increase nurses' competencies, and the latter seem to be strongly associated with attitudes. Thus, introducing palliative care education into nurses' core curricula could be a way to reduce anxiety and emotional distress in young students.

When people observe conflicting visual and proprioceptive cues about their static hand position, visuo-proprioceptive recalibration results. Recalibration also occurs during gradual or abrupt visuomotor adaptation, in response to both the cue conflict and sensory prediction errors experienced as the hand reaches to a target. Here we asked whether creating a cue conflict gradually vs. abruptly, or providing error feedback, affects recalibration in a static hand. We examined participants' responses to a 70 mm visuo-proprioceptive conflict, imposed by shifting the visual cue forward from the proprioceptive cue (static left hand). Participants pointed with their unseen right hand to indicate perceived bimodal and unimodal cue positions. Conflict was introduced gradually (groups 1 and 2) or abruptly (groups 3 and 4), with performance feedback present (groups 2 and 4) or absent (groups 1 and 3). For abrupt groups, most behavioral change occurred immediately after the conflict began. No-feedback groups (1 and 3) showed comparable magnitudes of overall recalibration, indicating that abrupt and gradual conflicts result in similar recalibration but with different timings. Motor adaptation was evident in the indicator hand with performance feedback (groups 2 and 4). However, performance on a static ruler task suggests proprioceptive recalibration also occurred despite the presence of feedback. Control groups confirmed accurate performance on the pointing task despite the visual cue shift. These findings highlight the distinct timing of recalibration mechanisms for gradual versus abrupt cue conflicts and potential smaller contribution of error mechanisms for a static conflict.

Background: Although tumor cells undergoing epithelial-mesenchymal transition (EMT) typically exhibit spindle morphology in experimental models, such histomorphological evidence of EMT has predominantly been observed in rare primary spindle carcinomas. The characteristics and transcriptional regulators of spontaneous EMT in genetically unperturbed non-spindled carcinomas remain underexplored., Methods: We used primary culture combined with RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq), and in situ RNA-seq to explore the characteristics and transcription factors (TFs) associated with potential spontaneous EMT in non-spindled breast carcinoma., Results: Our primary culture revealed carcinoma cells expressing diverse epithelial-mesenchymal traits, consistent with epithelial-mesenchymal plasticity. Importantly, carcinoma cells undergoing spontaneous EMT did not necessarily exhibit spindle morphology, even when undergoing complete EMT. EMT was a favored process, whereas mesenchymal-epithelial transition appeared to be crucial for secondary tumor growth. Through scRNA-seq, we identified TFs that were sequentially and significantly upregulated as carcinoma cells progressed through the EMT process, which correlated with increasing VIM expression. Once upregulated, the TFs remained active throughout the EMT process. ZEB1 was a key initiator and sustainer of EMT, as indicated by its earliest significant upregulation in the EMT process, its exact correlation with VIM expression, and the reversal of EMT and downregulation of EMT-upregulated TFs upon ZEB1 knockdown. The correlation between ZEB1 and vimentin expression in triple-negative breast cancer and metaplastic breast carcinoma tumor cohorts further highlighted its role. The immediate upregulation of ZEB2 following that of ZEB1, along with the observation that the knockdown of ZEB1 or ZEB2 downregulates both ZEB1 and ZEB2 concomitant with the reversal of EMT, suggests their functional cooperation in EMT. This finding, together with that of a lack of correlation of SNAI1, SNAI2, and TWIST1 expression with the mesenchymal phenotype, indicated EMT-TFs have a context-dependent role in EMT. Upregulation of EMT-related gene signatures during EMT correlated with poor patient outcomes, highlighting the biological importance of the model. Elevated EMT gene signatures and increased ZEB1 and ZEB2 expression in vimentin-positive compared to vimentin-negative carcinoma cells within the corresponding primary tumor tissue confirmed ZEB1 and ZEB2 as intrinsic, instead of microenvironmentally-induced, EMT regulators, and vimentin as an in vivo indicator of EMT., Conclusions: Our findings provide insights into the characteristics and transcriptional regulators of spontaneous EMT in primary non-spindled carcinoma., (© 2024. The Author(s).)

Adaptive metabolic switches are proposed to underlie conversions between cellular states during normal development as well as in cancer evolution. Metabolic adaptations represent important therapeutic targets in tumors, highlighting the need to characterize the full spectrum, characteristics, and regulation of the metabolic switches. To investigate the hypothesis that metabolic switches associated with specific metabolic states can be recognized by locating large alternating gene expression patterns, we developed a method to identify interspersed gene sets by massive correlated biclustering and to predict their metabolic wiring. Testing the method on breast cancer transcriptome datasets revealed a series of gene sets with switch-like behavior that could be used to predict mitochondrial content, metabolic activity, and central carbon flux in tumors. The predictions were experimentally validated by bioenergetic profiling and metabolic flux analysis of 13C-labeled substrates. The metabolic switch positions also distinguished between cellular states, correlating with tumor pathology, prognosis, and chemosensitivity. The method is applicable to any large and heterogeneous transcriptome dataset to discover metabolic and associated pathophysiological states. Significance: A method for identifying the transcriptomic signatures of metabolic switches underlying divergent routes of cellular transformation stratifies breast cancer into metabolic subtypes, predicting their biology, architecture, and clinical outcome., (©2024 The Authors; Published by the American Association for Cancer Research.)

Rationale: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency., Objective: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation., Methods: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years)., Results: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen's Kappa = 0.47 ± 0.07; P < 0.001). Nevertheless, self-reported and EHR-identified m/s-AECOPD events were both associated with higher BAL neutrophils (ß ± SEM: 3.0 ± 1.1 and 1.3 ± 0.5 per 10% neutrophil increase; P ≤ 0.018) and lymphocytes (0.9 ± 0.4 and 0.7 ± 0.3 per 10% lymphocyte increase; P ≤ 0.041). Exacerbation by either measure combined was associated with a larger estimated effect (3.7 ± 1.2 and 1.0 ± 0.5 per 10% increase in neutrophils and lymphocytes, respectively) but was not statistically significantly different compared to the self-report only approach. Among the 184 TEPS participants, there were fewer moderate to very severe respiratory exacerbations by self-report (n = 15 or 8%) or EHR-documentation (n = 9 or 5%), but a similar level of agreement as those with COPD was observed (Cohen's Kappa = 0.38 ± 0.07; P < 0.001)., Discussion: While there is modest agreement between self-reported and EHR-identified m/s-AECOPD, events are missed by relying on either method alone. However, m/s-AECOPD quantified by self-report or health records is associated with BAL neutrophilia and lymphocytosis., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: To determine anxiety and depression levels among pediatric acute care nurses and physicians before and after vaccine implementation during the coronavirus disease 2019 pandemic., Methods: Prospective cross-sectional study of emergency medicine and urgent care providers at a metropolitan quaternary pediatric emergency department, including 2 satellite emergency departments and 7 urgent care sites. Anxiety and depression symptoms were assessed using the Generalized Anxiety Disorder-7 and the Patient Health Questionnaire-2. Nurses and physicians were surveyed twice using the Generalized Anxiety Disorder-7 in May 2020 and March 2021 and once with the Patient Health Questionnaire-2 in March 2021., Results: In total, 189 surveys were completed in May 2020 (response rate 48%), and 243 surveys were completed in March 2021 (response rate 52%). Nurses reported higher Generalized Anxiety Disorder-7 scores compared to physicians for both years, though Patient Health Questionnaire-2 scores were similar. Mean Generalized Anxiety Disorder-7 scores decreased for both nurses and physicians between the 2 response periods. Amongst those who had a history of anxiety, chronic medical conditions, or were living with a high-risk individual, higher rates of anxiety were observed. Respondents endorsed the need for increased psychological support during a pandemic, with adequate and timely psychological support provided by the hospital, and stated their households were financially affected by the pandemic. Respondents reported fewer feelings of anxiety after self and public vaccination., Discussion: Study findings support increased psychological support for frontline nurses and physicians during a pandemic, particularly for those with a history of anxiety or chronic medical conditions, or those living with a high-risk individual., (Published by Elsevier Inc.)

Introduction: A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort., Methods: This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior to the start of ICI initiation and an on-treatment blood sample 15-180 days post ICI initiation. TF was calculated via an ensemble algorithm that utilizes TF estimates derived from variants and copy number information. Patients with molecular response (MR) were defined as patients with a ≥ 50% decrease in TF between tests. In the subset of patients with rw-imaging data between 2 and 18 weeks of ICI initiation, the predictive value of MR in addition to rw-imaging was compared to a model of rw-imaging alone., Results: The evaluable cohort (N = 86) was composed of 14 solid cancer types. Patients received either ICI monotherapy (38.4%, N = 33) or ICI in combination with chemotherapy (61.6%, N = 53). Patients with MR had significantly longer rw-overall survival (rwOS) (hazard ratio (HR) 0.4, P = 0.004) and rw-progression free survival (rwPFS) (HR 0.4, P = 0.005) than patients with molecular non-response (nMR). Similar results were seen in the ICI monotherapy subcohort; HR 0.2, P = 0.02 for rwOS and HR 0.2, P = 0.01 for rwPFS. In the subset of patients with matched rw-imaging data (N = 51), a model incorporating both MR and rw-imaging was superior in predicting rwOS than rw-imaging alone (P = 0.02)., Conclusions: xM used for TRM is a novel serial quantitative TF algorithm that can be used clinically to evaluate ICI therapy efficacy., (© 2024. The Author(s).)

Purpose: This exploratory study aimed to examine brain injury videos on YouTube to determine who posted about brain injury, content categories of videos, and how brain injury was represented., Methods: A mixed methods approach was used. Brain injury videos on YouTube were collected in November 2022 and analysed quantitatively and qualitatively using descriptive statistics and content analysis. Visual data analysis was used to generate visual descriptions of a representative sample of the videos, and these were thematically analysed alongside the video transcripts., Results: The sample of 100 YouTube videos consisted of educational, lived experience, and promotional videos. Medical organisations and hospitals were the predominant source of videos. An overarching theme of "Video tells a story" was generated from eighteen visual descriptions and transcripts which contained three major themes: (a) we choose how the story is told, (b) recovery is a process, and (c) it changed my life., Conclusion: YouTube may have a storytelling role for both people with a brain injury wishing to share their story and for health professionals wishing to communicate information about brain injury. This research may have clinical implications for the integration of YouTube in brain injury rehabilitation and the use of YouTube for health communication.

Primary encephaloceles are congenital mesodermal defects that result in brain tissue protruding through the skull. These defects most commonly occur occipitally but can be present anywhere in the calvarium. Meningoencephaloceles are a subclassification that includes herniation of the meninges. Basal meningoencephaloceles with cleft palate defects are the rarest form, with very few reports discussing anesthetic implications. We report a case of a giant basal meningoencephalocele that involves the nasal and oral cavities with a risk of thecal sac rupture., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 International Anesthesia Research Society.)

Objectives: The uptake of cochlear implants among adults who could benefit (based on pure-tone audiometry) in developed countries is estimated to be less than 10%. Concerns about potential surgical complications, fear of losing residual hearing, and limited awareness about the benefits of this intervention contribute to the low adoption rate. To enhance quality of life and improve the uptake of cochlear implants, it is essential to have a clear understanding of their benefits., Design: This umbrella review aims to summarize the major benefits of cochlear implant usage in adults, by synthesizing findings from published review articles. A comprehensive search of databases including MEDLINE, EMBASE, PsycINFO, and Google Scholar, was conducted. The search was limited to English-language review articles published between 1990 and 2022, focusing on cochlear implant outcomes in at least 5 adults (aged ≥18 years). Two independent reviewers screened titles, abstracts, and full-text articles, and conducted a quality assessment using the Joanna Briggs Checklist for Systematic Reviews and Research Syntheses., Results: Forty-two articles were included in this review. There were 15 systematic reviews with meta-analysis, 25 systematic reviews without meta-analysis, and 2 systematic scoping reviews. All 42 articles underwent quality assessment using the Joanna Briggs Institute Checklist for Systematic Reviews and Research Syntheses, of which 40% (n = 17) satisfied 9 out of 11 quality criteria. This umbrella review shows that cochlear implants are associated with improvements in speech perception and recognition as well as improved quality of life and cognition. These benefits are observed in a significant proportion of adults undergoing the procedure, highlighting its effectiveness as a viable intervention for individuals with severe to profound hearing loss., Conclusions: The potential benefits of cochlear implantation appear to outweigh the risks and complications associated with the procedure. It is recommended that adults with severe to profound hearing loss in particular, engage in informed discussions with healthcare professionals to consider cochlear implantation as a viable treatment option., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Insufficient exercise affects the health of patients who have implantable cardioverter defibrillators (ICD). The purpose of this study was to investigate the correlations between exercise self-efficacy (ESE) and its associated psychological factors in ICD recipients., Methods: This cross-sectional study included individuals who had undergone ICD implantation at the cardiology department of a medical centre in Taiwan. A face-to-face survey was conducted. The survey questionnaire included questions regarding the participants' demographics, perceived health (PH), ICD shock-related anxiety (ICD-SRA), self-care self-efficacy (SSE), perceived exercise benefit (PE-benefit), perceived exercise barrier (PE-barrier), and ESE. Data were analysed using SPSS 20.0 Software. Stepwise multiple regression analyses were also performed to evaluate the predictive effects of the aforementioned factors on ESE., Results: A total of 52 ICD recipients were enrolled. ESE was negatively correlated with ICD-SRA (r = -0.511; p < 0.01) and PE-barrier (r = -0.563; p < 0.01), but positively correlated with SSE (r = 0.339; p < 0.05) and PE-benefit (r = 0.464; p < 0.01). The stepwise multiple regression analysis revealed that PE-barrier, PE-benefit, and ICD-SRA effectively predicted ESE in the participants., Conclusions: ESE may be improved by overcoming PE-barrier, ICD-SRA and enhancing PE-benefit. Consequently, improving ESE may enhance the health benefits of exercise., Competing Interests: All authors report no conflicts of interest, (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Acute promyelocytic leukemia is a rare form of acute myeloid leukemia in which immature promyelocytes abnormally proliferate in the bone marrow. In most cases, the disease is characterised by the translocation t(15;17) (q24;q21), which causes the formation of PML::RARA, an oncogenic fusion protein responsible for blocking myeloid differentiation and survival advantage. Here, we present a case of acute promyelocytic leukemia with two unusual features: basophilic differentiation and a three-way translocation involving chromosomes 12, 15 and 17. In the few cases reported, basophilic differentiation was associated with a poor prognosis. In contrast, our patient responded promptly to the standard treatment with all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) and obtained complete remission. To our knowledge, this is the first report of basophilic acute promyelocytic leukemia with the three-way translocation t(12;17;15) (p13; q24;q21).

Background: Immunohistochemistry (IHC) and in situ hybridization (ISH) remain standard biomarkers for therapeutic decisions in human epidermal growth factor 2 (HER2)-positive breast cancers (BCs); however, they are insufficient to explain the heterogeneous anti-HER2 response., Methods: We aimed to investigate the correlation of in situ HER2 RNA expression (isHRE), using RNAscope, with HER2 biomarkers and the impact of isHRE on the pathological complete response (pCR) rates of 278 patients with HER2 IHC/fluorescence ISH (FISH)-positive BC receiving neoadjuvant chemotherapy and anti-HER2 targeted treatment (NCTT)., Results: We validated HER2 RNAscope scoring as a semiquantitative method to determine isHRE and showed a positive correlation between RNAscope scores and pCR rates, with particularly different rates between patients with a score of 5 versus 1-4 BCs (66.7% vs. 15.9%, p < 0.0001). There were higher RNAscope scores and pCR rates in patients with HER2 IHC 3 + versus IHC 2+/FISH + BCs and HER2 RNAscope scores and pCR rates showed similar non-linear positive correlations with HER2 copy numbers and HER2/centromere 17 ratios. Moreover, in each HER2-positive IHC/FISH category, higher pCR rates were observed in patients with RNAscope scores of 5 versus 1-4 BC. Patients achieving pCR had BCs with notably higher HER2 RNAscope scores. Multivariate analysis identified HER2 RNAscope 5 as a strong pCR predictor [odds ratio = 10.865, p < 0.001]. The combined impact of multivariate analysis-defined pCR predictors demonstrated that a higher pCR rate was observed in patients with a score of 5 versus a score of 1-4 BCs regardless of the status of hormone receptor and mono-or dual anti-HER2 blockade., Concusions: Our results demonstrated that high isHRE (RNAscope score 5) is a strong pCR predictor in patients with HER2-positive BCs receiving NCTT, highlighting the complementary role of isHRE in stratifying HER2 status in tissue. Such stratification is relevant to anti-HER2 therapeutic efficacy, particularly using the cutoff of score 1-4 versus 5., (© 2024. The Author(s).)

Automated online cognitive assessments are set to revolutionise clinical research and healthcare. However, their applicability for Parkinson's Disease (PD) and REM Sleep Behavioural Disorder (RBD), a strong PD precursor, is underexplored. Here, we developed an online battery to measure early cognitive changes in PD and RBD. Evaluating 19 candidate tasks showed significant global accuracy deficits in PD (0.65 SD, p = 0.003) and RBD (0.45 SD, p = 0.027), driven by memory, language, attention and executive underperformance, and global reaction time deficits in PD (0.61 SD, p = 0.001). We identified a brief 20-min battery that had sensitivity to deficits across these cognitive domains while being robust to the device used. This battery was more sensitive to early-stage and prodromal deficits than the supervised neuropsychological scales. It also diverged from those scales, capturing additional cognitive factors sensitive to PD and RBD. This technology offers an economical and scalable method for assessing these populations that can complement standard supervised practices., (© 2024. The Author(s).)

Purpose: To present an oral anesthesia protocol for in-office oculoplastic surgery and to compare safety outcomes and patient and physician experiences to ambulatory surgery center (ASC)-based surgery with intravenous sedation or general anesthesia., Methods: A prospective study was performed on consecutive patients undergoing surgery at an oculofacial plastic surgery practice. Surgery was performed in an in-office setting using our standardized oral sedation protocol or at an ASC with intravenous sedation or general anesthesia. Preoperative and postoperative surveys were conducted by patients and physicians to compare surgical experience, safety, and efficacy of our oral sedation protocol for in-office surgery in the ASC setting., Results: Two hundred and fifty-three patients (167 in-office and 86 at ASC) underwent surgery between March and November 2022. There was no significant difference in how patients or physicians rated their experience between the 2 locations. A significantly higher proportion of ASC patients would have rather had surgery in-office (34.9% vs. 19.2%; p = 0.006). A significantly higher number of physicians in the office setting would have rather performed surgery at the ASC than the reverse (12.7% vs. 2.3%, respectfully; p = 0.007). There were no safety complications reported in either setting., Conclusions: Within our patient cohort, the presented oral sedation protocol provided safe and effective anesthesia for in-office oculoplastic surgery that is comparable to an ASC., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

The popularity of social media platforms, such as Instagram, has given rise to a surge in photo editing and filtering practices among users. Understanding the underlying psychological factors that drive individuals to employ filters is crucial in comprehending the impact of such behavior on self-perception and online interactions. This study aims to investigate the influence of self-esteem on the importance attributed to the use of Instagram filters, with a particular focus on the mediating role played by the fear of negative evaluation. A sample of participants ( N  = 2,657) from diverse demographic backgrounds has been recruited to complete a series of questionnaires measuring self-esteem, fear of negative evaluation, and Instagram filter usage patterns. Mediation analysis has been employed to assess the extent to which the fear of negative evaluation mediates the relationship between self-esteem and filter usage importance. In line with the hypotheses, the results revealed that participants self-esteem negatively predicted fear of negative evaluation, which in turn had a positive effect on use of filters. Furthermore, fear of negative evaluation fully mediated the relationship between self-esteem and use of filters. Overall, the implications of this research extend to both theoretical and practical domains. The findings can contribute to the existing literature on self-esteem, social media behavior, and body image by shedding light on the factors influencing digital self-presentation., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lo Destro.)

Moiré patterns caused by aliasing between the camera's sensor and the monitor can severely degrade image quality. Image demoiréing is a multi-task image restoration method that includes texture and color restoration. This paper proposes a new multibranch wavelet-based image demoiréing network (MBWDN) for moiré pattern removal. Moiré images are separated into sub-band images using wavelet decomposition, and demoiréing can be achieved using the different learning strategies of two networks: moiré removal network (MRN) and detail-enhanced moiré removal network (DMRN). MRN removes moiré patterns from low-frequency images while preserving the structure of smooth areas. DMRN simultaneously removes high-frequency moiré patterns and enhances fine details in images. Wavelet decomposition is used to replace traditional upsampling, and max pooling effectively increases the receptive field of the network without losing the spatial information. Through decomposing the moiré image into different levels using wavelet transform, the feature learning results of each branch can be fully preserved and fed into the next branch; therefore, possible distortions in the recovered image are avoided. Thanks to the separation of high- and low-frequency images during feature training, the proposed two networks achieve impressive moiré removal effects. Based on extensive experiments conducted using public datasets, the proposed method shows good demoiréing validity both quantitatively and qualitatively when compared with the state-of-the-art approaches.

Adducts between OsO 4 and Lewis bases exert a role in important oxidation processes such as epoxidation and dihydroxylation. It has been shown that the attractive interaction driving the formation of these adducts is a σ-hole bond involving the metal as the electrophilic species; the term Osme Bond (OmB) was proposed for designating it. Here some new adducts between OsO 4 and various bases have been characterized through single crystal x-ray diffraction (XRD) and computational studies (density functional theory, DFT), confirming the existence of a robust correlation between σ-hole interaction energy and deformation of the tetrahedral geometry of OsO 4 . Also, some adducts formed by RuO 4 with nucleophiles were investigated computationally., (© 2024 Wiley‐VCH GmbH.)

Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing. We validate the performance with 80 pairs of deep and shallow-coverage whole-genome sequencing and whole-genome bisulfite sequencing data., (© 2024. The Author(s).)

In this manuscript, a comprehensive study is presented on Fe-based electrocatalysts with mono, bi, and tri-metallic compositions, emphasizing the influence of processing-structure correlations on the electrocatalytic activity for the oxygen reduction reaction (ORR) in the alkaline medium. These electrocatalysts were synthesized through the mixing of transition metal phthalocyanines (TM-Pc) with conductive carbon support, followed by controlled thermal treatment at specific temperatures (600 °C and 900 °C). An extensive analysis was conducted, employing various techniques, including X-ray Absorption Spectroscopy (XAS), Transmission Electron Microscopy (TEM), and X-ray Diffraction (XRD), providing valuable insights into the structural characteristics of the synthesized nanoparticles. Importantly, an increase in the Fe-Pc weight percentage from 10% to 30% enhanced the ORR activity, although not proportionally. Furthermore, a comparative analysis between mono, bi, and tri-metallic samples subjected to different functionalization temperatures highlighted the superior electrocatalytic activity of electrocatalysts functionalized at 600 °C, particularly Fe 600 and Fe-Ni-Cu 600. These electrocatalysts featured E on values of 0.96 V vs. RHE and E 1/2 values of 0.9 V vs. RHE, with the added benefit of reduced anionic peroxide production. The potential of these Fe-based electrocatalysts to enhance ORR efficiency is underscored by this research, contributing to the development of more effective and sustainable electrocatalysts for energy conversion technologies.

Amyotrophic Lateral Sclerosis (ALS) is a progressive disease with prevalent mitochondrial dysfunctions affecting both upper and lower motor neurons in the motor cortex, brainstem, and spinal cord. Despite mitochondria having their own genome (mtDNA), in humans, most mitochondrial genes are encoded by the nuclear genome (nDNA). Our study aimed to simultaneously screen for nDNA and mtDNA genomes to assess for specific variant enrichment in ALS compared to control tissues. Here, we analysed whole exome (WES) and whole genome (WGS) sequencing data from spinal cord tissues, respectively, of 6 and 12 human donors. A total of 31,257 and 301,241 variants in nuclear-encoded mitochondrial genes were identified from WES and WGS, respectively, while mtDNA reads accounted for 73 and 332 variants. Despite technical differences, both datasets consistently revealed a specific enrichment of variants in the mitochondrial Control Region (CR) and in several of these genes directly associated with mitochondrial dynamics or with Sirtuin pathway genes within ALS tissues. Overall, our data support the hypothesis of a variant burden in specific genes, highlighting potential actionable targets for therapeutic interventions in ALS.

Lignin, flavonoids, melatonin, and stilbenes are plant specialized metabolites with diverse physiological and biological functions, supporting plant growth and conferring stress resistance. Their biosynthesis requires O-methylations catalyzed by 5-hydroxyconiferaldehyde O-methyltransferase (CAldOMT; also called caffeic acid O-methyltransferase, COMT). CAldOMT was first known for its roles in syringyl (S) lignin biosynthesis in angiosperm cell walls and later found to be multifunctional. This enzyme also catalyzes O-methylations in flavonoid, melatonin, and stilbene biosynthetic pathways. Phylogenetic analysis indicated the convergent evolution of enzymes with OMT activities towards the monolignol biosynthetic pathway intermediates in some gymnosperm species that lack S-lignin and Selaginella moellendorffii, a lycophyte which produces S-lignin. Furthermore, neofunctionalization of CAldOMTs occurred repeatedly during evolution, generating unique O-methyltransferases (OMTs) with novel catalytic activities and/or accepting novel substrates, including lignans, 1,2,3-trihydroxybenzene, and phenylpropenes. This review summarizes multiple aspects of CAldOMTs and their related proteins in plant metabolism and discusses their evolution, molecular mechanism, and roles in biorefineries, agriculture, and synthetic biology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

This study endeavored to overcome the physiological barriers hindering optimal bioavailability in ophthalmic therapeutics by devising drug delivery platforms that allow therapeutically effective drug concentrations in ocular tissues for prolonged times. Thermosensitive drug delivery platforms were formulated by blending poloxamers (F68 and F127) with low-molecular-weight hyaluronic acid (HA) in various concentrations and loaded with hydrocortisone (HC). Among the formulations examined, only three were deemed suitable based on their desirable gelling properties at a temperature close to the eye's surface conditions while also ensuring minimal gelation time for swift ocular application. Rheological analyses unveiled the ability of the formulations to develop gels at suitable temperatures, elucidating the gel-like characteristics around the physiological temperature essential for sustained drug release. The differential scanning calorimetry findings elucidated intricate hydrogel-water interactions, indicating that HA affects the water-polymer interactions within the gel by increasing the platform hydrophilicity. Also, in vitro drug release studies demonstrated significant hydrocortisone release within 8 h, governed by an anomalous transport mechanism, prompting further investigation for optimized release kinetics. The produced platforms offer promising prospects for efficacious ocular drug delivery, addressing pivotal challenges in ocular therapeutics and heralding future advancements in the domain.

Purpose Giant hiatus hernia (GHH) repair is undertaken electively in symptomatic patients, to prevent complications such as gastric volvulus and subsequent mortality. Advances in laparoscopy and perioperative care have reduced the risk of GHH repair, and improvement in quality of life (QoL) has become an important outcome measure. In our unit, we have been assessing QoL in all the operated as well as non-operated patients with GHH, using the "Quality of Life in Reflux and Dyspepsia" (QOLRAD) questionnaire. We sought to evaluate differences in QoL between patients who were managed conservatively for GHH and those who underwent GHH repair over a two-year period. Methods All patients seen in the Upper Gastrointestinal Tertiary Unit in Lancashire Teaching Hospitals NHS Trust with GHH between January 2015 and December 2022 were identified from a prospectively kept database. QOLRAD scores were analyzed and compared between conservatively and operatively managed patients using the Mann-Whitney U test. Demographic and operative outcome data were also collected. Results Eighty-seven patients with GHH were included. QoL of 51 patients improved significantly after elective surgery. Five out of 36 patients, who were initially treated conservatively, elected to have repair during their follow-up period. These 5 Patients had a lower initial QOLRAD score in comparison to those whose management remained conservative (2.72 vs 5.05, Mann Whitney U test p=0.034), and their QOLRAD scores also improved significantly after the operation. QOLRAD scores in conservatively managed patients remained stable over a two-year follow-up period. Conclusion Objectively calculated low QoL may be a more useful tool than subjective symptoms in selecting patients for elective repair of GHH., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Elniel et al.)

Background: It is extremely rare for Lyme borreliosis to present solely with features of increased intracranial pressure. The treatment of pediatric Lyme neuroborreliosis with oral versus intravenous antibiotics remains controversial., Methods: Case report and literature review., Results: A 13-year-old male presented with five days of binocular diplopia, several weeks of headache, and a history of multiple tick bites six weeks prior. His examination showed a left eye abduction deficit and bilateral optic disc edema. Magnetic resonance imaging (MRI) of the brain with contrast showed tortuosity of the optic nerves, prominence of the optic nerve sheaths, and enhancement of the left fifth and bilateral sixth cranial nerves. Lumbar puncture showed an elevated opening pressure and a lymphocytic pleocytosis. Lyme IgM and IgG antibodies were positive in the serum and cerebrospinal fluid. The patient was treated with intravenous ceftriaxone for two days empirically followed by doxycycline by mouth for 19 days. Symptoms began improving after 48 hours. The strabismus resolved after two weeks, and the papilledema improved slowly with complete resolution at six months., Conclusions: Lyme neuroborreliosis can present as isolated intracranial hypertension in the pediatric population; it can be differentiated from idiopathic intracranial hypertension on MRI, and lumbar puncture and can be confirmed with serum antibody testing. Oral doxycycline can be considered for Lyme neuroborreliosis in children., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)