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AIM: Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. METHOD: We studied cross-sectionally 135 children with CZS aged 0 to 48 months, investigating sleep using the BISQ Questionnaire. Language development was assessed using the Early Language Milestone Scale, while motor development and cognitive and social ability were assessed using the Bayley Scales of Infant and Young Child Development 3rd edition. We also studied longitudinally a cohort of 16 children (initially aged 0 to 12 months) whom we followed for four years, assessing at one-year intervals. RESULTS: Sleep disturbances and language deficits were highly frequent in this population. In the 0–12 months group, a late bedtime and frequent nighttime awakenings were associated with poorer auditory expressive skills. At 13–24 months, nighttime awakenings were associated with poorer auditory expressive skills, while among 25–36-month-olds decreased auditory receptive skills were associated with longer sleep onset latency and reduced nighttime sleep duration. CONCLUSION: The brain alterations caused by Zika virus infection affect both sleep disturbances and delays in language development. It is possible that sleep disturbance may be a mediating factor in the pathway between CZS and delayed language development, as the three analyzed language skills showed a correlation with sleep parameters. [ABSTRACT FROM AUTHOR]

Nematodes of the genus Trichinella are important pathogens of humans and animals. This study aimed to enhance the genomic and transcriptomic resources for T. pseudospiralis (non-encapsulated phenotype) and T. spiralis (encapsulated phenotype) and to explore transcriptional profiles. First, we improved the assemblies of the genomes of T. pseudospiralis (code ISS13) and T. spiralis (code ISS534), achieving genome sizes of 56.6 Mb (320 scaffolds, and an N50 of 1.02 Mb) and 63.5 Mb (568 scaffolds, and an N50 value of 0.44 Mb), respectively. Then, for each species, we produced RNA sequence data for three key developmental stages (first-stage muscle larvae [L1s], adults, and newborn larvae [NBLs]; three replicates for each stage), analysed differential transcription between stages, and explored enriched pathways and processes between species. Stage-specific upregulation was linked to cellular processes, metabolism, and host–parasite interactions, and pathway enrichment analysis showed distinctive biological processes and cellular localisations between species. Indeed, the secreted molecules calmodulin, calreticulin, and calsyntenin—with possible roles in modulating host immune responses and facilitating parasite survival—were unique to T. pseudospiralis and not detected in T. spiralis. These insights into the molecular mechanisms of Trichinella–host interactions might offer possible avenues for developing new interventions against trichinellosis. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been a growing interest in the therapeutic potential of classical psychedelics like ayahuasca for mental health improvement. Naturalistic studies at ayahuasca retreats have shown (short-term) improvements in mental well-being but understanding the psychological mechanisms is crucial. We are interested in psychological processes such as resilience, self-compassion, and personality traits. Additionally, it is unclear whether changes are solely due to ayahuasca or influenced by the social setting. To address this, a control group participating in a breathwork session, similar to ayahuasca retreats, was included. Methods: In this observational study, individuals who attended an ayahuasca retreat (n = 69) and individuals who participated in a breathwork session (n = 30) completed an online survey one week before (baseline) and one, six, and twelve weeks after they entered the retreat/session. The survey included a series of questionnaires, i.e., the World Health Organisation-Five Well-Being Index, 14-item Resilience Scale, Self-Compassion Scale–Short Form, and Big Five Inventory-10. A linear mixed model (LMM) was used to analyze the outcome data. Results: It was shown that well-being, resilience, and self-compassion increased and remained stable over 12 weeks compared to baseline, regardless of group (ayahuasca or breathwork). Older participants generally reported higher resilience and self-compassion. Self-compassion was also higher in the ayahuasca group overall. Neuroticism decreased in both groups, with lower scores in the ayahuasca group. Agreeableness increased over time, also not influenced by group membership, while there were no changes in extraversion, conscientiousness, or openness. Discussion: Both interventions improved well-being, aligning with prior research. Importantly, this study unveils a novel finding: both interventions enhance resilience and self-compassion for up to three months, offering promise for conditions marked by low well-being, resilience, and self-compassion like depression and anxiety-related disorders. While acknowledging its limitations (e.g., self-selected sample, no specific information of the ayahuasca brew or the breathwork technique), it emphasizes the need for controlled studies with control groups, attention to social contexts in research on these interventions, and to assess other variables like depth of altered states of consciousness that might explain improvement in psychological processes and wellbeing. [ABSTRACT FROM AUTHOR]

The treatment of head and neck cancers (HNCs) encompasses a complex paradigm involving a combination of surgery, radiotherapy, and systemic treatment. Locoregional recurrence is a common cause of treatment failure, and few patients are suitable for salvage surgery. Reirradiation with conventional radiation techniques is challenging due to normal tissue tolerance limits and the risk of significant toxicities. Stereotactic body radiotherapy (SBRT) has emerged as a highly conformal modality that offers the potential for cure while limiting the dose to surrounding tissue. There is also growing research that shows that those with oligometastatic disease can benefit from curative intent local ablative therapies such as SBRT. This review will look at published evidence regarding the use of SBRT in locoregional recurrent and oligometastatic HNCs. [ABSTRACT FROM AUTHOR]

Simple Summary: Stereotactic body radiotherapy (SBRT) is a highly precise, non-invasive, and image-guided form of hypofractionated radiotherapy aimed at well-defined small targets. It is characterized by superior conformity of dose distribution, steep dose drop-off gradients, and short overall treatment time, which allow effective protection of surrounding normal tissue from high radiation doses, potentially resulting in lower toxicity and a more potent biological effect. Currently, SBRT is an established curative therapy for certain cancers and some benign tumors, as well as a valuable palliative option. There is limited experience with SBRT for de novo mucosal carcinoma of the head and neck. A systematic review of the literature and subsequent analysis of 124 patients from five studies treated between 2012 and 2020 confirmed that SBRT is an effective and relatively safe treatment for small tumor targets in de novo mucosal carcinoma of the head and neck. Standardization of SBRT practice and well-designed prospective clinical trials are highly needed. Stereotactic body radiotherapy (SBRT) is characterized by a high dose per fraction, well-defined small targets, superior dose conformity, and a steep off-target dose gradient. A literature search was conducted to examine the experience with SBRT as a curative treatment for newly diagnosed mucosal carcinoma of the head and neck (MCHN). Four retrospective case series and one prospective phase I clinical trial published between 2012 and 2020 described 124 patients. SBRT was mainly performed in older patients with different tumor sites. The median size of the planning target volumes ranged from 5.3 to 41 cm3. Different approaches were used to create margins. In two studies, limited elective nodal irradiation was performed. The equivalent doses used were 60–83.33 Gy delivered in five fractions. Considerable heterogeneity was observed in the radiation dose specification. The incidence of grade ≥3 late toxicity was 0–8.3%, with local and regional control ranging from 73% to 100%. Improved or stable quality of life after SBRT was reported in two studies. Curative-intent SBRT for de novo MCHN appears to be an effective and relatively safe treatment for small tumor targets, preferably without concomitant elective tissue irradiation. Standardization of SBRT practice and well-designed prospective clinical trials are needed to better define the role of SBRT in this setting. [ABSTRACT FROM AUTHOR]

Direct assessments of executive functions (EFs) are increasingly used in research and clinical settings, with a central assumption that they assess "universal" underlying skills. Their use is spreading globally, raising questions about the cultural appropriateness of assessments devised in Western industrialized countries. We selectively reviewed multidisciplinary evidence and theory to identify sets of cultural preferences that may be at odds with the implicit assumptions of EF assessments. These preferences relate to motivation and compliance; cultural expectations for interpersonal engagement; contextualized vs. academic thinking; cultural notions of speed and time; the willingness to be silly, be incorrect, or do the opposite; and subject-matter familiarity. In each case, we discuss how the cultural preference may be incompatible with the assumptions of assessments, and how future research and practice can address the issue. Many of the cultural preferences discussed differ between interdependent and independent cultures and between schooled and unschooled populations. Adapting testing protocols to these cultural preferences in different contexts will be important for expanding our scientific understanding of EF from the narrow slice of the human population that has participated in the research to date. [ABSTRACT FROM AUTHOR]

Excessive daytime sleepiness is a common symptom of sleep disorders. Despite its prevalence, it remains difficult to define, detect, and address. The difficulties surrounding sleepiness have been linked to an ambiguous conceptualization, a large variety of scales and measures, and the overlap with other constructs, such as fatigue. The present study aims to investigate patients' descriptions of sleepiness-related daytime complaints and their phenomenology. We performed semi-directed interviews with patients diagnosed with obstructive sleep apnea (N = 15) or narcolepsy (N = 5). The interviewers took care of utilizing the participants' terminology when describing daytime complaints related to their sleep disorder. Various aspects of the daytime complaints were investigated, such as their description and temporality. The transcribed content was thematically analyzed using an eclectic coding system, yielding five themes. The participants used different interchangeable descriptors (tired, sleepy, fatigued, exhausted) to express their daytime complaints. They enriched their description with indexes of magnitude (ranging from 'not especially' to 'most gigantic, extreme'), oppositions to other states (using antipodes like energy, alertness, wakefulness, or rest), and indications of fluctuations over the day. Interestingly, the participants often used metaphors to express their experiences and their struggles. The lived experiences of the patients were found to not always align with common self-reported monitoring tools of sleepiness and to relate only in part with current conceptions. In practice, it is important to probe daytime complaints, such as daytime sleepiness, with a broader consideration, for example, by exploring antipodes, consequences, and time-of-day fluctuations. [ABSTRACT FROM AUTHOR]

The severity of COVID-19 is linked to an imbalanced immune response. The dysregulated metabolism of small molecules and bioactive lipids has also been associated with disease severity. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyze over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). This is the third publication in a series, and it reports the results of comprehensive lipidome profiling using targeted LC-MS/MS. We identified 1076 lipid features across 25 subclasses, including glycerophospholipids, sterols, glycerolipids, and sphingolipids, among which 531 lipid features were dramatically changed in the plasma of intensive care unit (ICU) patients compared to patients in the ward. Patients in the ICU showed 1.3–57-fold increases in ceramides, (lyso-)glycerophospholipids, diglycerides, triglycerides, and plasmagen phosphoethanolamines, and 1.3–2-fold lower levels of a cyclic lysophosphatidic acid, sphingosine-1-phosphates, sphingomyelins, arachidonic acid-containing phospholipids, lactosylceramide, and cholesterol esters compared to patients in the ward. Specifically, phosphatidylinositols (PIs) showed strong fatty acid saturation-dependent behavior, with saturated fatty acid (SFA)- and monosaturated fatty acid (MUFA)-derived PI decreasing and polystaturated (PUFA)-derived PI increasing. We also found ~4000 significant Spearman correlations between lipids and multiple clinical markers of immune response with |R| ≥ 0.35 and FDR corrected Q < 0.05. Except for lysophosphatidic acid, lysophospholipids were positively associated with the CD4 fraction of T cells, and the cytokines IL-8 and IL-18. In contrast, sphingosine-1-phosphates were negatively correlated with innate immune markers such as CRP and IL-6. Further indications of metabolic changes in moderate COVID-19 disease were demonstrated in recovering ward patients compared to those at the start of hospitalization, where 99 lipid species were altered (6 increased by 30–62%; 93 decreased by 1.3–2.8-fold). Overall, these findings support and expand on early reports that dysregulated lipid metabolism is involved in COVID-19. [ABSTRACT FROM AUTHOR]

Oropharyngeal squamous cell carcinoma (OPSCC), a subset of head and neck squamous cell carcinoma (HNSCC), involves the palatine tonsils, soft palate, base of tongue, and uvula, with the ability to spread to adjacent subsites. Personalized treatment strategies for Human Papillomavirus-associated squamous cell carcinoma of the oropharynx (HPV+OPSCC) are yet to be established. In this article, we summarise our current understanding of the pathogenesis of HPV+OPSCC, the intrinsic role of the immune system, current ICI clinical trials, and the potential role of small molecule immunotherapy in HPV+OPSCC. [ABSTRACT FROM AUTHOR]

Invasive fungal (IF) diseases are a leading global cause of mortality, particularly among immunocompromised individuals. The SARS-CoV-2 pandemic further exacerbated this scenario, intensifying comorbid IF infections such as mucormycoses of the nasopharynx. In the work reported here, it is shown that zygomycetes, significant contributors to mycoses, are sensitive to the natural product allicin. Inhibition of Mucorales fungi by allicin in solution and by allicin vapor was demonstrated. Mathematical modeling showed that the efficacy of allicin vapor is comparable to direct contact with the commercially available antifungal agent amphotericin B (ampB). Furthermore, the study revealed a synergistic interaction between allicin and the non-volatile ampB. The toxicity of allicin solution to human cell lines was evaluated and it was found that the half maximal effective concentration (EC50) of allicin was 25–72 times higher in the cell lines as compared to the fungal spores. Fungal allicin sensitivity depends on the spore concentration, as demonstrated in a drop test. This study shows the potential of allicin, a sulfur-containing defense compound from garlic, to combat zygomycete fungi. The findings underscore allicin's promise for applications in infections of the nasopharynx via inhalation, suggesting a novel therapeutic avenue against challenging fungal infections. [ABSTRACT FROM AUTHOR]

To date, the scientific literature on health variables for Escherichia coli antimicrobial resistance (AMR) has been investigated throughout several systematic reviews, often with a focus on only one aspect of the One Health variables: human, animal, or environment. The aim of this umbrella review is to conduct a systematic synthesis of existing evidence on Escherichia coli AMR in humans in the community from a One Health perspective. PubMed, EMBASE, and CINAHL were searched on "antibiotic resistance" and "systematic review" from inception until 25 March 2022 (PROSPERO: CRD42022316431). The methodological quality was assessed, and the importance of identified variables was tabulated across all included reviews. Twenty-three reviews were included in this study, covering 860 primary studies. All reviews were of (critically) low quality. Most reviews focused on humans (20), 3 on animals, and 1 on both human and environmental variables. Antibiotic use, urinary tract infections, diabetes, and international travel were identified as the most important human variables. Poultry farms and swimming in freshwater were identified as potential sources for AMR transmission from the animal and environmental perspectives. This umbrella review highlights a gap in high-quality literature investigating the time between variable exposure, AMR testing, and animal and environmental AMR variables. [ABSTRACT FROM AUTHOR]

Introduction: Hemivertebrae are a common defect of vertebral formation, potentially resulting in debilitating congenital scoliosis and necessitating highly traumatic surgery. Virtual surgical planning (VSP) and 3D-printed patient-specific implants (PSIs) have increasingly been applied to complex spinal surgery, and offer a range of potential benefits. Research Question: We report the use of 3D-printed PSIs and VSP as part of a two-level anterior lumbar interbody fusion (ALIF) for the management of lateral hemivertebra and congenital scoliosis. Material and Methods: A 53-year-old male with chronic low-back pain, due to L4 hemivertebra and mild congenital scoliosis, presented with new-onset leg pain. CT revealed L4/5 and L5/S1 degeneration and foraminal stenosis. Given the complex anatomy and extensive multi-level osteophytosis, 3D-printed PSIs were designed, manufactured, and implanted as part of a two-level ALIF. Results: Excellent implant fit was achieved intraoperatively, confirmed via postoperative imaging. VSP assisted with navigating challenging bony and vascular anatomy. Three-month postoperative imaging demonstrated construct stability, early signs of bony fusion, with implant placement, spinal curvature, and disc height corrections closely matching the VSP. Clinically, the patient’s pain and functional impairment had effectively resolved by nine-month follow up, as demonstrated through subjective and objective measures. Discussion and Conclusions: Virtual surgical planning and 3D-printed PSIs can be useful surgical aids in the management of the often-complex cases involving hemivertebrae and congenital scoliosis. This case of congenital pathology adds to the growing reports of PSI application to a variety of complex spinal pathologies, with analyses showing a close match of the postoperative construct to the preoperative VSP. [ABSTRACT FROM AUTHOR]

This article explores the unique environmental ethos advocated by Dharma Drum Mountain (DDM), an international Buddhist spiritual, cultural, and education foundation founded by the late Chan Master Sheng Yen. It presents a critical reflection on orthodox models of Western environmental ethics and illuminates the constraints of mainstream critical approaches when confronted with the intricate ecological philosophies embedded in Buddhist traditions. Central to the DDM's model is the profound interweaving of spiritual cultivation with environmental consciousness, a stance that fosters a multidimensional dialogue that engages various ecological narratives. This approach not only resonates with aspects of Western environmental thought but is also firmly grounded in a distinct philosophical tradition that emphasizes spiritual growth as integral to genuine ecological engagement. In this article, it is argued that DDM's holistic initiatives necessitate an expanded, diversified environmental discourse that accommodates a spectrum of cultural and philosophical insights. Consequently, this examination serves a dual purpose: it provides an insight into DDM's environmental philosophy, and it can stimulate a paradigm shift while urging consideration beyond conventional boundaries and advocating for a spiritually inclusive approach to environmental awareness and preservation. [ABSTRACT FROM AUTHOR]

Current safety data on chemotherapy during pregnancy are based on studies which focus on the mother and do not explore reproductive health and fecundity potential within the exposed offspring. We designed this randomized ex vivo animal study to evaluate the effect of chemotherapy on the developing ovarian reserve in the exposed offspring. Specimens (100 postnatal day zero C57BL/6 mouse ovaries) were randomized to control or chemotherapy drug exposure and maintained in a hanging well organ culture. Murine ovarian reserve establishment mirrors activity seen in the human fetus but with a significant time shift of the transition to meiotic arrest to the postnatal period. Exposures included: doxorubicin, cyclophosphamide, paclitaxel, docetaxel, and cisplatin. Doxorubicin resulted in a significant loss of 95.2% (p < 0.0001) of oocyte density compared to controls. Cyclophosphamide also caused depletion of 50.5% (p < 0.0001) of oocyte density. Cisplatin, docetaxel, and paclitaxel all demonstrated unique phenotypical changes on the ovaries and their oocytes, without a significant decrease in oocyte density over a five-day exposure. Exposure to chemotherapy may result in profound loss of oogonia during the transition to mature oocytes. [ABSTRACT FROM AUTHOR]

Simple Summary: Oropharyngeal dysphagia (OD), malnutrition, sarcopenia, and frailty often co-occur with head-and-neck cancer (HNC) and may affect treatment outcomes, but the presence, severity, and consequences of these phenomena vary from patient to patient. It is a challenge to predict which patients have a higher risk of these phenomena, and early identification using a 'quick and easy' multi-domain screening may allow us to obtain a more holistic view of the patient's risk profile, enabling the prevention of complications and prehabilitation before the start of cancer treatment. The aim of our study was to identify the prevalence of the risk of OD, malnutrition, sarcopenia, and frailty and their co-occurrence in all newly diagnosed HNC patients. More than three quarters of the 128 patients were at risk for OD, malnutrition, sarcopenia, and/or frailty. The advanced cancer stage was related to an increased risk of OD and higher levels of distress. Background: Head-and-neck cancer (HNC) can give rise to oropharyngeal dysphagia (OD), malnutrition, sarcopenia, and frailty. Early identification of these phenomena in newly diagnosed HNC patients is important to reduce the risk of complications and to improve treatment outcomes. The aim of this study was (1) to determine the prevalence of the risk of OD, malnutrition, sarcopenia, and frailty; and (2) to investigate the relation between these phenomena and patients' age, performance status, and cancer group staging. Methods: Patients (N = 128) underwent multi-domain screening consisting of the Eating Assessment Tool-10 for OD, Short Nutritional Assessment Questionnaire and BMI for malnutrition, Short Physical Performance Battery and Hand Grip Strength for sarcopenia, and Distress Thermometer and Maastricht Frailty Screening Tool for frailty. Results: 26.2%, 31.0%, 73.0%, and 46.4% of the patients were at risk for OD, malnutrition, sarcopenia, or frailty, respectively. Patients with an advanced cancer stage had a significantly higher risk of OD and high levels of distress prior to cancer treatment. Conclusions: This study identified the risk profile of newly diagnosed HNC patients using a standardized 'quick and easy' multi-domain screening prior to cancer treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy is emerging as an improved systemic treatment for select patients with advanced unresectable hepatocellular carcinoma. An objective response is reported in 30% of patients, yet a complete response allowing for curative-intent surgery is rare. Locoregional therapies seem to show synergistic effects with immunotherapy, though this effect has not been scientifically reported. We report a cohort of patients showing a complete response to this combination immunotherapy + LRT and aim to present this as a proposed treatment approach for locally unresectable disease. We also report how liquid biopsy using ctDNA was cleared using this approach and discuss how this testing modality may assist patients with this type of disease. Background: Immunotherapy has emerged as an improved systemic treatment for select patients with advanced unresectable HCC. Objective response is reported in 30% of patients, yet complete response (pCR) allowing for curative-intent resection is rare. Locoregional therapies (LRTs) seem to show synergistic effects with immunotherapy, though this effect has not been scientifically reported. We report a cohort of patients showing pCR to immunotherapy + LRT as a proof of concept for the proposed treatment approach for locally unresectable HCC. Methods: Patients with unresectable HCC treated with immunotherapy as an intended destination therapy from 2016 to 2023 were included. The electronic health record was queried for oncologic information, locoregional therapies, surgical interventions, and long-term outcomes. Circulating tumor DNA (ctDNA) testing was obtained using Guardant360, and tumor mutational burden (TMB) was defined as the number of somatic mutations per megabase. Results: Ninety-six patients with advanced HCC received immunotherapy + LRT as a destination therapy. In total, 11 of 96 patients showed a complete response according to mRECIST criteria. Four of these (36.4%) ultimately underwent curative-intent resection. The median follow-up was 24.9 (IQR 15.6–38.3) months. Overall survival rates in those with complete response at 1, 3, and 5 years were 100%, 91%, and 81.8%, respectively, which were significantly improved compared to those of the cohort not achieving pCR (p < 0.001). All four patients undergoing immunotherapy + LRT followed by curative-intent hepatectomy have no evidence of disease (NED). Of those undergoing surgery, ctDNA was cleared in 75% (n = 3), providing an additional objective measurement of complete response. All four patients were TMB+ before beginning this treatment course, with three being TMB-, indicating stable and complete disease response. Conclusions: Immunotherapy + locoregional therapy can help downstage a significant proportion of patients with initially unresectable HCC, allowing for curative-intent surgery. The survival benefit associated with complete response seems durable up to 3 years after achieving this response. ctDNA measurement was converted from positive to negative in this cohort, providing additional indication of response. [ABSTRACT FROM AUTHOR]

Nondisplaced femoral neck fractures are sometimes misdiagnosed by radiographs, which may deteriorate into displaced fractures. However, few efficient artificial intelligent methods have been reported. We developed an automatic detection method using deep learning networks to pinpoint femoral neck fractures on radiographs to assist physicians in making an accurate diagnosis in the first place. Our proposed accurate automatic detection method, called the direction-aware fracture-detection network (DAFDNet), consists of two steps, namely region-of-interest (ROI) segmentation and fracture detection. The first step removes the noise region and pinpoints the femoral neck region. The fracture-detection step uses a direction-aware deep learning algorithm to mark the exact femoral neck fracture location in the region detected in the first step. A total of 3840 femoral neck parts in anterior–posterior (AP) pelvis radiographs collected from the China Medical University Hospital database were used to test our method. The simulation results showed that DAFDNet outperformed the U-Net and DenseNet methods in terms of the IOU value, Dice value, and Jaccard value. Our proposed DAFDNet demonstrated over 94.8% accuracy in differentiating non-displaced Garden type I and type II femoral neck fracture cases. Our DAFDNet method outperformed the diagnostic accuracy of general practitioners and orthopedic surgeons in accurately locating Garden type I and type II fracture locations. This study can determine the feasibility of applying artificial intelligence in a clinical setting and how the use of deep learning networks assists physicians in improving correct diagnoses compared to the current traditional orthopedic manual assessments. [ABSTRACT FROM AUTHOR]

We developed an improved, robust synthesis of a series of pillar[6]arenes with a varying number (0–3) of quinone moieties in the ring. This easy-to-control variation yielded a gradually less electron-rich cavity in going from zero to three quinone units, as shown from the strength of host–guest interactions with silver ions. Such macrocycle-Ag2 complexes themselves were shown to display an unprecedented, sharp distinction between terminal alkynes, which strongly bound to such complexes, and internal alkynes, internal alkenes and terminal alkenes, which do hardly bind. [ABSTRACT FROM AUTHOR]

Bone morphogenetic protein (BMP) gene delivery to Lewis rat lumbar intervertebral discs (IVDs) drives bone formation anterior and external to the IVD, suggesting the IVD is inhospitable to osteogenesis. This study was designed to determine if IVD destruction with a proteoglycanase, and/or generating an IVD blood supply by gene delivery of an angiogenic growth factor, could render the IVD permissive to intra-discal BMP-driven osteogenesis and fusion. Surgical intra-discal delivery of naïve or gene-programmed cells (BMP2/BMP7 co-expressing or VEGF165 expressing) +/- purified chondroitinase-ABC (chABC) in all permutations was performed between lumbar 4/5 and L5/6 vertebrae, and radiographic, histology, and biomechanics endpoints were collected. Follow-up anti-sFlt Western blotting was performed. BMP and VEGF/BMP treatments had the highest stiffness, bone production and fusion. Bone was induced anterior to the IVD, and was not intra-discal from any treatment. chABC impaired BMP-driven osteogenesis, decreased histological staining for IVD proteoglycans, and made the IVD permissive to angiogenesis. A soluble fragment of VEGF Receptor-1 (sFlt) was liberated from the IVD matrix by incubation with chABC, suggesting dysregulation of the sFlt matrix attachment is a possible mechanism for the chABC-mediated IVD angiogenesis we observed. Based on these results, the IVD can be manipulated to foster vascular invasion, and by extension, possibly osteogenesis. [ABSTRACT FROM AUTHOR]

Simple Summary: Genome-wide DNA methylation profiling has emerged as an important diagnostic tool that complements histopathology for characterizing central nervous system (CNS) tumors. The literature describing its application in Asian countries is limited. We report the feasibility and utility of adopting such profiling for children with diagnosed CNS tumors in Hong Kong. The study included samples of 97 patients with CNS embryonal or high-grade neuroepithelial tumors (HGNETs). In our DNA methylation-profiled cohort, 67% of results correlated with the diagnosis and assigned molecular subgroup and 12% of results led to revision/reassignment of diagnosis. Patient outcomes correlated significantly with methylation-based subgroups. In addition, novel clinical–histologic–molecular associations were described. Taken together, epigenomic profiling enabled clinically relevant refinement of disease classification of pediatric CNS tumors. The availability of such methodology in Asia sets the stage for international collaborations in molecularly driven trials. This paper examines the link between CNS tumor biology and heterogeneity and the use of genome-wide DNA methylation profiling as a clinical diagnostic platform. CNS tumors are the most common solid tumors in children, and their prognosis remains poor. This study retrospectively analyzed pediatric patients with CNS embryonal tumors in Hong Kong between 1999 and 2017, using data from the territory-wide registry and available formalin-fixed paraffin-embedded tumor tissue. After processing archival tumor tissue via DNA extraction, quantification, and methylation profiling, the data were analyzed by using the web-based DKFZ classifier (Molecular Neuropathology (MNP) 2.0 v11b4) and t-SNE analysis. Methylation profiles were deemed informative in 85 samples. Epigenetic data allowed molecular subgrouping and confirmed diagnosis in 65 samples, verified histologic diagnosis in 8, and suggested an alternative diagnosis in 12. This study demonstrates the potential of DNA methylation profiling in characterizing pediatric CNS embryonal tumors in a large cohort from Hong Kong, which should enable regional and international collaboration in future pediatric neuro-oncology research. [ABSTRACT FROM AUTHOR]

The prognosis of colorectal cancer patients with peritoneal metastases is very poor. Intraperitoneal drug delivery systems, like supramolecular hydrogels, are being developed to improve local delivery and intraperitoneal residence time of a cytostatic such as mitomycin C (MMC). In this study, we evaluate the effect of intraperitoneal hydrogel administration on anastomotic healing. Forty-two healthy Wistar rats received a colonic end-to-end anastomosis, after which 6 animals received an intraperitoneal injection with saline, 18 with unloaded hydrogel and 18 with MMC-loaded hydrogel. After 7 days, animals were euthanized, and the anastomotic adhesion and leakage score were measured as primary outcome. Secondary outcomes were bursting pressure, histological anastomosis evaluation and body weight changes. Twenty-two rats completed the follow-up period (saline: n = 6, unloaded hydrogel: n = 10, MMC-loaded hydrogel: n = 6) and were included in the analysis. A trend towards significance was found for anastomotic leakage score between the rats receiving saline and unloaded hydrogel after multiple-comparison correction (p = 0.020, α = 0.0167). No significant differences were found for all other outcomes. The main reason for drop-out in this study was intestinal blood loss. Although the preliminary results suggest that MMC-loaded or unloaded hydrogel does not influence anastomotic healing, the intestinal blood loss observed in a considerable number of animals receiving unloaded and MMC-loaded hydrogel implies that the injection of the hydrogel under the studied conditions is not safe in the current rodent model and warrants further optimalisation of the hydrogel. [ABSTRACT FROM AUTHOR]

The gut microbiota, including bacteria, archaea, fungi, and viruses, compose a diverse mammalian gut environment and are highly associated with host health. Bacteriophages, the viruses that infect bacteria, are the primary members of the gastrointestinal virome, known as the phageome. However, our knowledge regarding the gut phageome remains poorly understood. In this review, the critical role of the gut phageome and its correlation with mammalian health were summarized. First, an overall profile of phages across the gastrointestinal tract and their dynamic roles in shaping the surrounding microorganisms was elucidated. Further, the impacts of the gut phageome on gastrointestinal fitness and the bacterial community were highlighted, together with the influence of diets on the gut phageome composition. Additionally, new reports on the role of the gut phageome in the association of mammalian health and diseases were reviewed. Finally, a comprehensive update regarding the advanced phage benchwork and contributions of phage-based therapy to prevent/treat mammalian diseases was provided. This study provides insights into the role and impact of the gut phagenome in gut environments closely related to mammal health and diseases. The findings provoke the potential applications of phage-based diagnosis and therapy in clinical and agricultural fields. Future research is needed to uncover the underlying mechanism of phage–bacterial interactions in gut environments and explore the maintenance of mammalian health via phage-regulated gut microbiota. [ABSTRACT FROM AUTHOR]

Ants belonging to the genus Solenopsis are highly significant invasive pests worldwide. The control of these insects has historically relied on the use of synthetic insecticides, which, unfortunately, has led to a range of ecological repercussions. In light of these challenges and the limited availability of registered products for managing these pests, our study set out to synthesize and assess the insecticidal properties of carvacrol derivatives. The lethal and sublethal effects caused by these derivatives were compared to the essential oil of Lippia gracilis (50.7% carvacrol) and to the base molecule—carvacrol. Carvacryl benzoate was the most toxic derivative to Solenopsis sp., with an LD50 of 3.20 μg/ mg. This compound was about 2 and 7.6 times more toxic than carvacrol at the doses needed to kill 50 and 90% of populations, respectively. The workers of Solenopsis sp. showed a rapid reduction in survival when exposed to carvacrol (LT50 = 8.43 h) and carvacryl benzoate (LT50 = 8.87 h). Insects treated with sublethal doses of the compounds did not show significant effects on self-cleaning, allogrooming and aggregation, with the exception of those treated with L. gracilis essential oil. The oil increased self-cleaning and reduced allogrooming and aggregation. Ants treated with carvacrol and carvacryl benzoate travelled greater distances and had higher movement speeds when compared to the control. These compounds exhibited decreased meanders and angular velocities. When live workers were exposed to dead individuals at the LD90 of the compounds, carvacryl benzoate was the derivative that most reduced survival due to horizontal transfer. These findings underscore the considerable potential of carvacrol derivatives, specifically carvacryl benzoate, as an alternative approach to managing ants of the Solenopsis genus. [ABSTRACT FROM AUTHOR]

Simple Summary: Instead of extensive conventional surgical resection, early-stage colorectal cancers are now often primarily treated using specialized local resection techniques, such as the endoscopic submucosal dissection (ESD). Sometimes after ESD a regular surgical resection is still needed. However, the impact of ESD on this surgery has not been well studied yet. This study aimed to investigate if ESD affected the safety and outcome of completion surgery. Outcomes of two groups of patients were compared: one consisting of patients who only had an upfront surgical resection and another consisting of patients who had an ESD followed by a surgical resection. Results showed that safety and outcome of surgery were similar in both groups. This means that ESD does not significantly increase negative outcomes of surgery. This knowledge empowers doctors to perform ESD as a first treatment option for early-stage colorectal cancers. T1 colorectal cancers (T1CRC) are increasingly being treated by endoscopic submucosal dissection (ESD). After ESD of a T1CRC, completion surgery is indicated in a subgroup of patients. Currently, the influence of ESD on surgical morbidity and mortality is unknown. The aim of this study was to compare 90-day morbidity and mortality of completion surgery after ESD to primary surgery. The completion surgery group consisted of suspected T1CRC patients from a multicenter prospective ESD database (2014–2020). The primary surgery group consisted of pT1CRC patients from a nationwide surgical registry (2017–2019). Patients with rectal or sigmoidal cancers were selected. Patients receiving neoadjuvant therapy were excluded. Propensity score adjustment was used to correct for confounders. In total, 411 patients were included: 54 in the completion surgery group (39 pT1, 15 pT2) and 357 in the primary surgery group with pT1CRC. Adverse event rate was 24.1% after completion surgery and 21.3% after primary surgery. After completion surgery 90-day mortality did not occur, though one patient died in the primary surgery group. After propensity score adjustment, lymph node yield did not differ significantly between the groups. Among other morbidity-related outcomes, stoma rate (OR 1.298 95%-CI 0.587-2.872, p = 0.519) and adverse event rate (OR 1.162; 95%-CI 0.570-2.370, p = 0.679) also did not differ significantly. A subgroup analysis was performed in patients undergoing rectal surgery. In this subgroup (37 completion and 136 primary surgery), these morbidity outcomes also did not differ significantly. In conclusion, this study suggests that ESD does not compromise morbidity or 90-day mortality of completion surgery. [ABSTRACT FROM AUTHOR]

In this study, we develop an innovative method that assists computer-aided diagnosis in the determination process of the exact location of the femoral neck junction in plain radiographs. Our algorithm consists of two phases, i.e., coarse prediction and fine matching, which are implemented by supervised deep learning method and unsupervised clustering, respectively. In coarse prediction, standard masks are first produced by a specialist and trained in our proposed feature propagation network (FPU-Net) with supervised learning on the femoral neck dataset. In fine matching, the standard masks are first classified into different categories using our proposed three parameters with unsupervised learning. The predicted mask from FPU-Net is matched with each category of standard masks by calculating the values of intersection of union (IOU), and finally the predicted mask is substituted by the standard mask with the largest IOU value. A total of 4320 femoral neck parts in anterior–posterior (AP) pelvis radiographs collected from China Medical University Hospital database were used to test our method. Simulation results show that, on the one hand, compared with other segmentation methods, the method proposed in this paper has a larger IOU value and better suppression of noise outside the region of interest; on the other hand, the introduction of unsupervised learning for fine matching can help in the accurate localization segmentation of femoral neck images. Accurate femoral neck segmentation can assist surgeons to diagnose and reduce the misdiagnosis rate and burden. [ABSTRACT FROM AUTHOR]

In this study, we use real-world data to explore trends in antibiotic use in a dynamic cohort of long-term care (LTC) residents. A cross-sectional retrospective analysis of pharmacy medication supply records of 3459 LTC residents was conducted from 31 May 2016 to 31 May 2019. The primary outcome was the monthly prevalence of residents with an antibiotic episode. Secondary outcomes were the type of antibiotic used and duration of use. Over the three-year study period, residents were supplied 10460 antibiotics. On average, 18.9% of residents received an antibiotic monthly. Antibiotic use decreased slightly over time with a mean of 168/1000 (95% CI 146–177) residents using at least one antibiotic per month in June 2016 to 148/1000 (95% CI 127–156) in May 2019. The total number of antibiotic days per 100 resident days remained relatively constant over the study period: 8.8 days in 2016–2017, 8.4 in 2017–2018 and 6.4 in 2018–2019. Prolonged durations exceeding 100 days were seen for a small percentage of residents. We found extensive antibiotic use, which is a recognized contributor to antimicrobial resistance development, underscoring the necessity for quality treatment guidelines in this vulnerable population. [ABSTRACT FROM AUTHOR]

(1) Background: Percutaneous microwave ablation (MWA) is an accepted treatment of non-operative liver cancer. This study compares the ablation zones of four commercially available 2.45 GHz MWA systems (Emprint, Eco, Neuwave, and Solero) in an ex vivo porcine liver model. (2) Methods: Ex vivo porcine livers (n = 85) were obtained. Two ablation time setting protocols were evaluated, the manufacturer's recommended maximum time and a 3 min time, performed at the manufacturer-recommended maximum power setting. A total of 236 ablation samples were created with 32 (13.6%) samples rejected. A total of 204 samples were included in the statistical analysis. (3) Results: For single-probe protocols, Emprint achieved ablation zones with the largest SAD. Significant differences were found in all comparisons for the 3 min time setting and for all comparisons at the 10 min time setting except versus Neuwave LK15 and Eco. Emprint produced ablation zones that were also significantly more spherical (highest SI) than the single-probe ablations from all other manufacturers. No statistical differences were found for ablation shape or SAD between the single-probe protocols for Emprint and the three-probe protocols for Neuwave. (4) Conclusions: The new Emprint HP system achieved large and spherical ablation zones relative to other 2.45 GHz MWA systems. [ABSTRACT FROM AUTHOR]

Lithium-ion batteries (LIBs) are widely used in electrical vehicles (EVs), but safety issues with LIBs still occur frequently. State of charge (SOC) and state of health (SOH) are two crucial parameters for describing the state of LIBs. However, due to inconsistencies that may occur among hundreds to thousands of battery cells connected in series and parallel in the battery pack, these parameters can be difficult to estimate accurately. To address this problem, this paper proposes a joint SOC and SOH estimation method based on the nonlinear state space reconstruction (NSSR) and long short-term memory (LSTM) neural network. An experiment testbed was set up to measure the SOC and SOH of battery packs under different criteria and configurations, and thousands of charging/discharging cycles were recorded. The joint estimation algorithms were validated using testbed data, and the errors for SOC and SOH estimation were found to be within 2.5% and 1.3%, respectively, which is smaller than the errors obtained using traditional Ah-Integral and LSTM-only algorithms. [ABSTRACT FROM AUTHOR]

Not only leaves but also other plant organs and structures typically considered as carbon sinks, including stems, roots, flowers, fruits and seeds, may exhibit photosynthetic activity. There is still a lack of a coherent and systematized body of knowledge and consensus on the role(s) of photosynthesis in these "sink" organs. With regard to fruits, their actual photosynthetic activity is influenced by a range of properties, including fruit anatomy, histology, physiology, development and the surrounding microclimate. At early stages of development fruits generally contain high levels of chlorophylls, a high density of functional stomata and thin cuticles. While some plant species retain functional chloroplasts in their fruits upon subsequent development or ripening, most species undergo a disintegration of the fruit chloroplast grana and reduction in stomata functionality, thus limiting gas exchange. In addition, the increase in fruit volume hinders light penetration and access to CO2, also reducing photosynthetic activity. This review aimed to compile information on aspects related to fruit photosynthesis, from fruit characteristics to ecological drivers, and to address the following challenging biological questions: why does a fruit show photosynthetic activity and what could be its functions? Overall, there is a body of evidence to support the hypothesis that photosynthesis in fruits is key to locally providing: ATP and NADPH, which are both fundamental for several demanding biosynthetic pathways (e.g., synthesis of fatty acids); O2, to prevent hypoxia in its inner tissues including seeds; and carbon skeletons, which can fuel the biosynthesis of primary and secondary metabolites important for the growth of fruits and for spreading, survival and germination of their seed (e.g., sugars, flavonoids, tannins, lipids). At the same time, both primary and secondary metabolites present in fruits and seeds are key to human life, for instance as sources for nutrition, bioactives, oils and other economically important compounds or components. Understanding the functions of photosynthesis in fruits is pivotal to crop management, providing a rationale for manipulating microenvironmental conditions and the expression of key photosynthetic genes, which may help growers or breeders to optimize development, composition, yield or other economically important fruit quality aspects. [ABSTRACT FROM AUTHOR]

Leaf-cutting ants are important pests of agricultural and forest crops. Currently, few insecticides are registered for the control of these insects. Natural bioactive molecules can serve as models for the synthesis of new insecticidal compounds. Such ant killer products must be sustainable and efficient, considering not only lethal effects, but also sublethal effects, which can interfere with behavior and communication between colony members. In this study, we analyzed the toxicity of the monoterpene thymol and its derivatives, as well as the sublethal effects of these compounds on the behavior of the leaf-cutting ant Acromyrmex balzani. These effects were compared with the conventional synthetic insecticide deltamethrin. Although deltamethrin showed higher toxicity (LD50 = 0.87 × 10−5 µg/mg), all other tested compounds increased ant mortality, with thymyl chloroacetate being the most toxic derivative (LD50 = 1.41 µg/mg), followed by thymol (LD50 = 2.23 µg/mg). These three most toxic compounds interfered differentially in the behavior of ants. Thymyl chloroacetate caused increased self-cleaning and reduced allogrooming, which may be related to an attempt to avoid contamination between nestmates. In general, thymol caused greater avoidance among ants, reduced walking speed and caused disorientation in workers. On the other hand, thymyl chloroacetate (LD30) considerably increased the walking speed of the group, without changing the orientation of the individuals. Such changes may interfere with basic activities such as foraging and altering colony cohesion via different mechanisms. Thus, despite the desirable effects of deltamethrin on ant control, this insecticide is highly toxic and should be discontinued soon. Our results show that thymol and its structural modification in thymyl chloroacetate may represent potential ant killers to be used in the management of A. balzani. [ABSTRACT FROM AUTHOR]

A projected rise in patients with complex health needs and a rapidly ageing population will place an increased burden on the healthcare system. Care coordination can bridge potential gaps during care transitions and across the care continuum to facilitate care integration and the delivery of personalised care. Despite having a national strategic vision of improving care integration across different levels of care and community partners, there is no consolidation of evidence specifically on the salient dimensions of care coordination in the Singapore healthcare context. Hence, this scoping review aims to uncover the key themes that facilitate care coordination for patients with chronic conditions in Singapore to be managed in the community while illuminating under-researched areas in care coordination requiring further exploration. The databases searched were PubMed, CINAHL, Scopus, Embase, and Cochrane Library. Results from Google Scholar were also included. Two independent reviewers screened articles in a two-stage screening process based on the Cochrane scoping review guidelines. Recommendation for inclusion was indicated on a three-point scale and rating conflicts were resolved through discussion. Of the 5792 articles identified, 28 were included in the final review. Key cross-cutting themes such as having standards and guidelines for care programmes, forging stronger partnerships across providers, an interoperable information system across care interfaces, strong programme leadership, financial and technical resource availabilities and patient and provider-specific factors emerged. This review also recommends leveraging these themes to align with Singapore's national healthcare vision to contain rising healthcare costs. [ABSTRACT FROM AUTHOR]

The aim of this work is to improve the understanding of the effect of the cooling rate on the microstructure of high-entropy alloys, with a focus on high-entropy alloy coatings, by using a combined computational and experimental validation approach. CoCrFeMnNi0.8V coatings were deposited on a steel substrate with high velocity oxy-air-fuel spray with the employment of three different deposition temperatures. The microstructures of the coatings were studied and compared with the microstructure of the equivalent bulk high-entropy alloy fabricated by suction casting and powder fabricated by gas atomization. According to the results, the powder and the coatings deposited by low and medium temperatures consisted of a BCC microstructure. On the other hand, the microstructure of the coating deposited by high temperature was more complex, consisting of different phases, including BCC, FCC and oxides. The phase constitution of the bulk high-entropy alloy included an FCC phase and sigma. This variation in the microstructural outcome was assessed in terms of solidification rate, and the results were compared with Thermo-Calc modelling. The microstructure can be tuned by the employment of rapid solidification techniques such as gas atomization, as well as subsequent processing such as high velocity oxy-air-fuel spray with the use of different spray parameters, leading to a variety of microstructural outcomes. This approach is of high interest for the field of high-entropy alloy coatings. [ABSTRACT FROM AUTHOR]

The packaging nets used for bell peppers act as a form of protection. However, the manufacturing is based on polymers that cause serious environmental problems. The effects of nets made of biodegradable materials, such as poly(lactic) acid (PLA), poly(butylene adipate-co-terephthalate) (PBAT), and cactus stem residues, were evaluated on four different colors of 'California Wonder' bell peppers stored over a 25-day storage period under controlled and ambient temperature conditions. Compared to commercial polyethylene nets, the bell peppers kept in the biodegradable nets did not show notable differences with respect to color, weight loss, total soluble solids, and titratable acidity. However, there were significant differences (p < 0.05) in terms of phenol content, carotenoids (orange bell peppers), anthocyanins, and vitamin C, with an overall tendency to show a higher content in those kept in PLA 60%/PBTA 40%/cactus stem flour 3% compared to commercial packaging. In addition, the same net notably reduced the development of bacteria, fungi, and yeasts during the storage of red, orange, and yellow bell peppers. As postharvest packaging for bell peppers, this net could be considered a viable option for the storage of this product. [ABSTRACT FROM AUTHOR]

Enhancement in chemisorption is one of the active research areas in carbon materials. To remedy the thermally degraded chemisorption occurring at high temperatures, we report a comprehensive study of kink structures in free-standing monoatomic carbon nanowires upon heating. Our Monte Carlo simulation considers multi-monoatomic carbon chains laterally interacting by van der Waals forces. Our study reveals that carbon nanowires maintain their linearity regardless of chain length at low temperatures, but this is not the case at high temperatures. Disordered kink structure is observed in short carbon chains, especially above the Peierls transition temperature. A severe kink structure may increase the possibility of attaching negatively charged atoms, thereby contributing to the development of next-generation materials for chemisorption at high temperatures. We have also provided an important indication that any physical property of the finite-length carbon chain predicted by ab initio calculation should reconsider the atomic rearrangement due to thermal instability at high temperatures. [ABSTRACT FROM AUTHOR]

Desmoplastic small round cell tumor is a very rare and highly aggressive soft tissue sarcoma, usually presenting with multiple intra-abdominal tumors in young males. Patients present with advanced disease and the overall survival is dismal. Multiple studies report relatively favorable outcomes with multimodal treatment consisting of chemotherapy, surgery and radiotherapy. If resection is feasible, complete cytoreductive surgery is the cornerstone of surgical treatment. The benefit of hyperthermic intraperitoneal chemotherapy in addition to cytoreductive surgery is unclear, and few studies have evaluated this option. We sought to identify the role of hyperthermic intraperitoneal chemotherapy in patients with intra-abdominal desmoplastic small round cell tumor. Our review of the available literature revealed no clear survival benefit in performing hyperthermic intraperitoneal chemotherapy after cytoreductive surgery. [ABSTRACT FROM AUTHOR]

This study proposed wavelet-based approaches to characterise random vibration road excitations for durability prediction of coil springs. Conventional strain-life approaches require long computational time, while the accuracy of the vibration fatigue methods is unsatisfactory. It is therefore a necessity to establish an accurate fatigue life prediction model based on vibrational features. Wavelet-based methods were applied to determine the low-frequency energy and multifractality of road excitations. Strain-life models were applied for fatigue life evaluation from strain histories. ANFIS modelling was subsequently adopted to associate the vibration features with the fatigue life of coil springs. Results showed that the proposed wavelet-based methods were effective to determine the signal energy and multifractality of vibration signals. The established vibration-based models showed good fatigue life conservativity with a data survivability of more than 90%. The highest Pearson coefficient of 0.955 associated with the lowest RMSE of 0.660 was obtained by the Morrow-based model. It is suggested that the low-frequency energy and multifractality of the vibration signals can be used as fatigue-related features in life predictions of coil springs under random loading. Finally, the proposed model is an acceptable fatigue life prediction method based on vibration features, and it can reduce the dependency on strain data measurement. [ABSTRACT FROM AUTHOR]

This work details an effective dynamic chemical etching technique to fabricate ultra-sharp tips for Scanning Near-Field Microwave Microscopy (SNMM). The protruded cylindrical part of the inner conductor in a commercial SMA (Sub Miniature A) coaxial connector is tapered by a dynamic chemical etching process using ferric chloride. The technique is optimized to fabricate ultra-sharp probe tips with controllable shapes and tapered down to have a radius of tip apex around ∼1 μ m. The detailed optimization facilitated the fabrication of reproducible high-quality probes suitable for non-contact SNMM operation. A simple analytical model is also presented to better describe the dynamics of the tip formation. The near-field characteristics of the tips are evaluated by finite element method (FEM) based electromagnetic simulations and the performance of the probes has been validated experimentally by means of imaging a metal-dielectric sample using the in-house scanning near-field microwave microscopy system. [ABSTRACT FROM AUTHOR]

Reported here is the synthesis of a macrocycle with equatorial coordination sites for the construction of self-assembled metallacages. The macrocycle is prepared via a post-modification on the equator of biphen[n]arene. Utilizing this macrocycle as a ligand, three prismatic cages and one octahedral cage were synthesized by regulating the geometric structures and coordination number of metal acceptors. The multi-cavity configuration of prismatic cage was revealed by single-crystal structure. We prove that a macrocycle with equatorial coordination sites can be an excellent building block for synthesizing structure-diverse metallacages. Our results provide a typical example and a general method for the design and synthesis of metallacages. [ABSTRACT FROM AUTHOR]

Although many bacterial lipases and PHA depolymerases have been identified, cloned, and characterized, there is very little information on the potential application of lipases and PHA depolymerases, especially intracellular enzymes, for the degradation of polyester polymers/plastics. We identified genes encoding an intracellular lipase (LIP3), an extracellular lipase (LIP4), and an intracellular PHA depolymerase (PhaZ) in the genome of the bacterium Pseudomonas chlororaphis PA23. We cloned these genes into Escherichia coli and then expressed, purified, and characterized the biochemistry and substrate preferences of the enzymes they encode. Our data suggest that the LIP3, LIP4, and PhaZ enzymes differ significantly in their biochemical and biophysical properties, structural-folding characteristics, and the absence or presence of a lid domain. Despite their different properties, the enzymes exhibited broad substrate specificity and were able to hydrolyze both short- and medium-chain length polyhydroxyalkanoates (PHAs), para-nitrophenyl (pNP) alkanoates, and polylactic acid (PLA). Gel Permeation Chromatography (GPC) analyses of the polymers treated with LIP3, LIP4, and PhaZ revealed significant degradation of both the biodegradable as well as the synthetic polymers poly(ε-caprolactone) (PCL) and polyethylene succinate (PES). [ABSTRACT FROM AUTHOR]

The evaluation of serological responses to COVID-19 is crucial for population-level surveillance, developing new vaccines, and evaluating the efficacy of different immunization programs. Research and development of point-of-care test technologies remain essential to improving immunity assessment, especially for SARS-CoV-2 variants that partially evade vaccine-induced immune responses. In this work, an impedimetric biosensor based on the immobilization of the recombinant trimeric wild-type spike protein (S protein) on zinc oxide nanorods (ZnONRs) was employed for serological evaluation. We successfully assessed its applicability using serum samples from spike-based COVID-19 vaccines: ChAdOx1-S (Oxford–AstraZeneca) and BNT162b2 (Pfizer–BioNTech). Overall, the ZnONRs/ spike-modified electrode displayed accurate results for both vaccines, showing excellent potential as a tool for assessing and monitoring seroprevalence in the population. A refined outcome of this technology was achieved when the ZnO immunosensor was functionalized with the S protein from the P.1 linage (Gamma variant). Serological responses against samples from vaccinated individuals were acquired with excellent performance. Following studies based on traditional serological tests, the ZnONRs/spike immunosensor data reveal that ChAdOx1-S vaccinated individuals present significantly less antibody-mediated immunity against the Gamma variant than the BNT162b2 vaccine, highlighting the great potential of this point-of-care technology for evaluating vaccine-induced humoral immunity against different SARS-CoV-2 strains. [ABSTRACT FROM AUTHOR]

Implant infections caused by Staphylococcus aureus are difficult to treat due to biofilm formation, which complicates surgical and antibiotic treatment. We introduce an alternative approach using monoclonal antibodies (mAbs) targeting S. aureus and provide evidence of the specificity and biodistribution of S.-aureus-targeting antibodies in a mouse implant infection model. The monoclonal antibody 4497-IgG1 targeting wall teichoic acid in S. aureus was labeled with indium-111 using CHX-A"-DTPA as a chelator. Single Photon Emission Computed Tomography/computed tomographyscans were performed at 24, 72 and 120 h after administration of the 111In-4497 mAb in Balb/cAnNCrl mice with a subcutaneous implant that was pre-colonized with S. aureus biofilm. The biodistribution of this labelled antibody over various organs was visualized and quantified using SPECT/CT imaging, and was compared to the uptake at the target tissue with the implanted infection. Uptake of the 111In-4497 mAbs at the infected implant gradually increased from 8.34 %ID/cm3 at 24 h to 9.22 %ID/cm3 at 120 h. Uptake at the heart/blood pool decreased over time from 11.60 to 7.58 %ID/cm3, whereas the uptake in the other organs decreased from 7.26 to less than 4.66 %ID/cm3 at 120 h. The effective half-life of 111In-4497 mAbs was determined to be 59 h. In conclusion, 111In-4497 mAbs were found to specifically detect S. aureus and its biofilm with excellent and prolonged accumulation at the site of the colonized implant. Therefore, it has the potential to serve as a drug delivery system for the diagnostic and bactericidal treatment of biofilm. [ABSTRACT FROM AUTHOR]

Bacteriophages are viruses that infect bacteria and archaea and are classified as virulent or temperate phages based on their life cycles. A temperate phage, also known as a lysogenic phage, integrates its genomes into host bacterial chromosomes as a prophage. Previous studies have indicated that temperate phages are beneficial to their susceptible bacterial hosts by introducing additional genes to bacterial chromosomes, creating a mutually beneficial relationship. This article reviewed three primary ways temperate phages contribute to the bacterial pathogenicity of foodborne pathogens, including phage-mediated virulence gene transfer, antibiotic resistance gene mobilization, and biofilm formation. This study provides insights into mechanisms of phage–bacterium interactions in the context of foodborne pathogens and provokes new considerations for further research to avoid the potential of phage-mediated harmful gene transfer in agricultural environments. [ABSTRACT FROM AUTHOR]

Background: In various cancer types, the first step towards extended metastatic disease is the presence of lymph node metastases. Imaging methods with sufficient diagnostic accuracy are required to personalize treatment. Lymph node metastases can be detected with ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI), but this method needs validation. Here, a workflow is presented, which is designed to compare MRI-visible lymph nodes on a node-to-node basis with histopathology. Methods: In patients with prostate, rectal, periampullary, esophageal, and head-and-neck cancer, in vivo USPIO-enhanced MRI was performed to detect lymph nodes suspicious of harboring metastases. After lymphadenectomy, but before histopathological assessment, a 7 Tesla preclinical ex vivo MRI of the surgical specimen was performed, and in vivo MR images were radiologically matched to ex vivo MR images. Lymph nodes were annotated on the ex vivo MRI for an MR-guided pathological examination of the specimens. Results: Matching lymph nodes of ex vivo MRI to pathology was feasible in all cancer types. The annotated ex vivo MR images enabled a comparison between USPIO-enhanced in vivo MRI and histopathology, which allowed for analyses on a nodal, or at least on a nodal station, basis. Conclusions: A workflow was developed to validate in vivo USPIO-enhanced MRI with histopathology. Guiding the pathologist towards lymph nodes in the resection specimens during histopathological work-up allowed for the analysis at a nodal basis, or at least nodal station basis, of in vivo suspicious lymph nodes with corresponding histopathology, providing direct information for validation of in vivo USPIO-enhanced, MRI-detected lymph nodes. [ABSTRACT FROM AUTHOR]

Simple Summary: Traditionally, local treatment of lung cancers mainly consists of three branches: surgical resection, radiotherapy, and percutaneous ablation. With the advent of new technologies such as electromagnetic navigation bronchoscopy and robotic bronchoscopy, transbronchial therapies are being developed. This gives substantial hope to high-risk patients, especially those who have had prior chest radiation exposure or frail patients who could not tolerate surgery, as they would otherwise be excluded from the currently established forms of local treatment. In addition, demand for local ablation is also rising due to an increasing incidence of multiple synchronous lung cancers arising in the same patient. In this review, we discuss state-of-the-art transbronchial techniques for lung cancer treatment. The demand for parenchyma-sparing local therapies for lung cancer is rising owing to an increasing incidence of multifocal lung cancers and patients who are unfit for surgery. With the latest evidence of the efficacy of lung cancer screening, more premalignant or early-stage lung cancers are being discovered and the paradigm has shifted from treatment to prevention. Transbronchial therapy is an important armamentarium in the local treatment of lung cancers, with microwave ablation being the most promising based on early to midterm results. Adjuncts to improve transbronchial ablation efficiency and accuracy include mobile C-arm platforms, software to correct for the CT-to-body divergence, metal-containing nanoparticles, and robotic bronchoscopy. Other forms of energy including steam vapor therapy and pulse electric field are under intensive investigation. [ABSTRACT FROM AUTHOR]