Scar pregnancy is a rare and potentially life-threatening condition that occurs when an embryo implants and grows within a previous cesarean section scar or other uterine scars. This unique form of ectopic pregnancy poses significant diagnostic and management challenges for healthcare providers. Scar pregnancies are associated with an increased risk of uterine rupture, massive hemorrhage, and other complications, underscoring the importance of early detection and appropriate management strategies . Scar pr


Discoid lupus erythematosus (DLE) is a chronic variant of cutaneous lupus erythematous developing on sun-exposed areas in multi-morphic forms making diagnosis challenging. Clinical suspicion and prompt treatment are necessary to avoid permanent disfigurement, progression to systemic involvement and poor quality of life. We report a case of delayed DLE diagnosis in a 45-year-old man who presented with a new skin lesion mimicking the early stages of mycosis fungoides that prompted further investigation. Histopathological examination confirmed DLE and appropriate treatment was initiated. However, the atypical clinical presentation led to disseminated DLE and refractory disease control, resulting in scarring and cosmetic disfigurement. Lupus erythematosus (LE) is an autoimmune disease existing on a spectrum of cutaneous and systemic manifestations. Discoid lupus erythematosus (DLE) is the most common variant of chronic cutaneous LE that can present in a variety of morphologies . UnderstA 45-year-old male presented with a new erythematous plaque on the left upper chest after an initial diagnosis of photodermatitis due to the presence of erythematous patches and plaques on the scalp . The newA 4-millimeter punch biopsy from lesional skin showed an orthokeratotic and mildly atrophic epidermis with extensive vacuolar degeneration of the basal layer. There was a dense superficial dermal lichenoid-type of lymphocytic inflammatory infiltrate with scattered melanophages and presence of colloid bodies . Marked Histopathological findings coupled with serological findings were corroborative of DLE and thus the patient was started on short-term oral steroids with prednisolone (20 mg daily), oral hydroxychloroquine (HCQ)  and high-potency topical steroid clobetasol propionate. Treatment included photoprotection recommendations.At a 6-week follow-up, new cutaneous lesions appeared on the back  and the Patient’s systemic evaluation was negative to date. The patient is under regular follow-up with dermatology and rheumatology.DLE renders difficulty in clinical suspicion and definitive diagnosis as skin lesions resemble common dermatoses. It can lead to permanent disfigurement with hair loss, dyspigmentation and scarring if not treated early or adequately controlled. The chronic nature of the disease imposes a psychological burden and high morbidity on patients, often requiring psychosocial support , 4. Diag


Neural oscillatory activity has emerged as a central Research Topic in neuroscience  and phase . Despite their conceptually clear-cut operationalization, analyses of these parameters are confronted with an inherent problem: For which frequency range should these parameters be calculated and how should this range be determined? Initially, a priori-defined frequency ranges centered on a prominent power peak were linked to behaviorally relevant functions , has the potential to overcome the above-mentioned limitations. Computation of PF allows definition of recording-specific frequency peaks based on the empirical data, which can be used to compare individuals and/or experimental conditions. Additionally, when paired with novel tools correcting for aperiodic signal components  and discrete perception . Correlation analyses revealed no systematic connection between individual alpha PF and the latency of neural markers of visual processing. These findings indicate that individual alpha PF does not systematically shift early sensory processing in time.Two of the four contributions to this Research Topic examine the link between individual alpha PF and visual processing. Strang et al. assessed if individual alpha-band PFs over occipitoparietal  and sensorimotor  areas are linked to autism spectrum disorders. EEG recordings of neurotypical participants during motor execution and movement observation revealed that individuals with slower sensorimotor PFs exhibited higher autism-spectrum traits. This finding adds important information about potential biomarkers, since research so far largely focused on the classical alpha rhythm. The work by Sponheim et al. recorded individual alpha-band PFs with MEG during rest and visual processing in participants with psychotic psychopathology, their biological siblings, and healthy controls. Alpha PF varied widely across participants and remained temporally stable across multiple months. Moreover, slowed alpha PF was linked to longer visual percept duration in participants with psychopathology, as well as to lower IQ estimates and higher symptom severity. This study shows how fundamental research can inspire a directed functional assessment of neural markers as indicators of clinical symptom severity.Two other contributions studied the link between PFs and trait variables related to neuropsychiatric disorders. The systematic and hypothesis-driven analysis of PF holds the potential to provide exciting and novel roles of neural oscillatory activity. It promises to strengthen the analysis of oscillatory power and phase by providing an empirically-informed frame of reference instead of rigid a priori defined frequency definitions. We hope that this Research Topic has increased the visibility of PF in the neuroscientific audience and motivated future research.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Cell, Gungabeesoon and colleagues1 demonstrated that a specific subpopulation of neutrophils, characterized by a distinct Sellhi (CD62Lhi) phenotype with an interferon gene signature, acutely accumulates in tumors during successful immunotherapy and is associated with better treatment outcome. These findings enhance our understanding of the neutrophil heterogeneity within the tumor context and highlight their potential in cancer immunotherapy.In a recent study published in Traditionally, neutrophil infiltration of tumor tissue has been primarily associated with tumor progression. However, the remarkable heterogeneity of neutrophils allows them to play multiple roles in this process. In addition to their typical pro-angiogenic and immunosuppressive functions, neutrophils can also have protective roles, such as direct cancer cell killing or stimulation of adaptive immune responses. Importantly, various anti-cancer therapies directly or indirectly (by modulation of tumor microenvironment), impact neutrophil responses and activity. Nevertheless, some immunotherapies fail to induce clinical responses in certain patients, prompting extensive efforts to understand the underlying mechanisms.1 analyzed neutrophil phenotypes expanded after successful immunotherapy. These cells had been previously overlooked in single-cell transcriptomic research due to unintended elimination during standard preparation of the sample. The authors observed that therapy-induced neutrophils expressed high levels of Sell transcripts, encoding the protein Selectin L . These neutrophils exhibited a more immature phenotype (CD101lo), associated with increased cytotoxicity and upregulated expression of genes responsible for regulation of neutrophil degranulation, suggesting their potential immunostimulatory activity. This aligns with prior observations indicating anti-tumoral properties of immature neutrophil populations.2Sellhi neutrophils also exhibited a distinct interferon (IFN) signature, including interferon regulatory factor 1 (IRF1), a crucial driver of their anti-tumor phenotype, and appeared to be essential for the successful therapy , was sustained in tumors after treatment, even as Sellhi neutrophils increased. SiglecFhi neutrophils were previously shown to have pro-tumorigenic properties.5 Here the authors showed that these neutrophils were characterized by multiple gene signatures that support their pro-tumorigenic roles, including expression of genes that promote tumor proliferation, remodeling of extracellular matrix, angiogenesis, suppression of antitumor immunity, and recruitment of myeloid cells, and thus reported to be responsible for metastasizing, sustained in tumors after treatment. Therefore, this study suggests that therapies should aim not only to expand anti-tumor neutrophils, but also to eliminate pro-tumor counterparts. Further human studies will be needed however to understand the dynamics of these populations in a relevant clinical setting following therapy. Human studies should also allow evaluating whether the abundance of these neutrophil populations predict progression and outcome in human cancers.The authors also noted that another population of neutrophils, Single-cell transcriptomics has revolutionized our understanding of neutrophil biology by unraveling the phenotypical and functional diversity of neutrophil subsets across various organs. The pursuit of selective strategies to therapeutically enhance beneficial neutrophil populations while concurrently eliminating tumor-supporting neutrophils remains a compelling approach in immunotherapy. Rather than complete depletion of neutrophils, successful immunotherapy should focus on modulating the tumor microenvironment to favor anti-cancer repolarization of neutrophils. This approach holds the potential to establish an effective strategy for achieving optimal anti-tumor responses and enhancing the outcomes of cancer patients.


Dear colleagues,Pediatric minimally invasive surgery (MIS) epitomizes a dynamic and continuously evolving field that encompasses a broad range of procedures. From fetoscopic interventions in the prenatal population to robotic-assisted bariatric surgeries in overweight adolescents, the spectrum of techniques and patients encountered in pediatric MIS reflects its inherent intricacy and the fascination it inspires.In the context of this particular Special Issue, our primary objective revolved around an extensive exploration of the expansive landscape of pediatric MIS. This comprehensive investigation encompassed a wide range of relevant aspects, including well-established procedures, pioneering and audacious concepts—even those yielding unfavorable outcomes, breakthrough technological advancements, potential hazards and challenges, contentious procedures, and invaluable insights drawn from our counterparts in the realms of general, thoracic, and visceral surgery.Our intention was to transcend a simple retrospective appraisal by eschewing the common narrative of “what has been accomplished thus far?”. Instead, our aim was to assemble a compendium of reports from pioneering colleagues from diverse medical disciplines. These individuals have forged innovatively ahead, propelling developments in minimally invasive surgical interventions in order to enhance the welfare of pediatric patients.We are pleased to say that our endeavors have borne fruit, and we believe that we have achieved our objective.To improve the wellbeing of pediatric patients even before their birth, Thomas Kohl delves into the study of fetal surgery, offering insights into both established and emerging minimally invasive approaches. Expanding upon this, Susanne Eva Brunner provides an exhaustive review comparing bimanual techniques and procedures in fetal surgery with single-instrument interventions. Additionally, Lidya-Olgu Durmaz sheds light on the use of minimally invasive techniques in fetal surgery for the treatment of gastroschisis.Regarding infants and congenital malformations, Anne-Sophie Holler describes the endoscopic magnetic-assisted anastomosing technique, specifically designed for the repair of esophageal atresia. Additionally, Julia Küppers presents an innovative approach termed “endoscopic percutaneous rectal anoplasty”, which has garnered considerable attention from the esteemed Alberto Pena, a prominent authority on anorectal malformation repair, prompting subsequent scholarly discourse. In a closely related context, Ulrike Metzger provides valuable insights into a recently modified approach involving transanal endoscopic-assisted pull-through colectomy targeted toward pediatric patients afflicted by high intestinal aganglionosis. These developments in pediatric surgical interventions offer promising avenues for improved outcomes and enhanced patient care.When it comes to general pediatric surgical procedures, this comprehensive compilation includes many notable contributions. Hanna Noemi Stundner Ladenhauf presents a meticulous evaluation of the minimally invasive approach in managing traumatic pancreatic ruptures, shedding light on its efficacy and potential benefits. Armin-Johannes Michel provides a detailed account of the thoracoscope-guided pericostal suture technique, showcasing its efficacy as a robust fixation method for closing congenital diaphragmatic hernias. The state-of-the-art of advancements in the field of minimally invasive repair of pectus excavatum (MIRPE) is expertly detailed by Frank-Martin Haecker, as he reveals the current developments and techniques employed in this realm. In a similar vein, Christian Tomuschat delves into the boundaries and limitations encountered in laparoscopic partial splenectomy, providing valuable insights into the challenges associated with this minimally invasive procedure.The domain of pediatric surgery encompasses not only general procedures but also extends to minimally invasive urological interventions. In this context, Frank-Martin Haecker contributes valuable insights by reporting on the combined antegrade and retrograde endoscopic injection technique into the bladder neck employed in children with neurogenic bladder disorders. Furthermore, Christian Kruppa presents a fascinating approach to vesicoscopic cross-trigonal ureteral reimplantation, specifically addressing vesicoureteral reflux. This innovative technique offers a compelling avenue for the treatment and resolution of this condition. These advancements in minimally invasive urological procedures within pediatric surgery hold great promise for enhanced patient outcomes and an improved quality of care.Mareike Grosshauser contributes an insightful examination of interdisciplinary knowledge transfer within the study of minimally invasive pediatric surgery. Similarly, Tatjana Tamara König delves into the topic of telementoring in the context of minimally invasive esophageal atresia repair, shedding light on the potential benefits and implications of this approach. Expanding our understanding, Andrea Schmedding presents a comprehensive nationwide assessment of the current landscape surrounding laparoscopic pediatric inguinal hernia surgery, drawing upon an extensive dataset. Furthermore, Małgorzata Sobol offers a unique perspective by focusing on the parental experience of minimally invasive surgery, specifically examining the role of parents’ time perspective as a predictive factor for their child’s postsurgical pain and emergence delirium, and the potential manifestation of post-traumatic stress disorder in parents.The integration of robotic-assisted surgery will be pivotal element in the future landscape of minimally invasive pediatric surgical procedures. Ewan Brownlee and Mark Slack delve into this paradigm-shifting subject, offering an insightful report on the novel Versius surgical robotic system developed by Cambridge Medical (CMR), exploring its potential utility within the pediatric population. In a related investigation, Marit Kayser presents an evaluation of the Versius system for pediatric surgery, employing inanimate models that simulate small infants and, thus, providing valuable insights into its feasibility and effectiveness. Within the pages of this publication, we also encounter a groundbreaking contribution by Jürgen Holzer, who provide the world’s inaugural account of a pediatric pyeloplasty performed using the Senhance® robotic system. This pioneering achievement marks a significant milestone in the application of robotic technology in the pediatric surgical domain. Additionally, Elisabeth Ammer explores the phenomenon of “robotic anxiety” and elucidate parents’ perception of robot-assisted pediatric surgery and its impact on their children. This investigation sheds light on the psychological aspects and human factors associated with the adoption of robotic systems in pediatric surgical contexts. Finally, Thomas Krebs offers a comprehensive review encompassing diverse aspects of robotic-assisted pediatric surgery. Our collective insights and synthesis of existing knowledge serve to enrich our understanding and foster advancements in this rapidly evolving field.Nevertheless, the possibilities of minimally invasive pediatric surgery transcend the traditional boundaries of abdominal and thoracic procedures. Within the field of pediatric orthopedics and orthopedic trauma, Karsten Krohn unveils a pioneering technique involving the dual pre-bending of an intramedullary nail to treat diametaphyseal fractures of the distal radius in children. This innovative approach not only renders the procedure and osteosynthesis less invasive but also holds promise for improved patient outcomes. Moreover, the use of resorbable implants presents an intriguing possibility for circumventing the need for subsequent explantation surgeries; this is an area explored by Christoph Roeder. Through a pilot study, he investigates the application of biodegradable intramedullary nailing, specifically for forearm fractures in the pediatric population. His findings shed light on the feasibility and potential benefits of this approach, paving the way for future advancements in pediatric orthopedic interventions. Similarly, Pascal Heye contributes to this line of inquiry by delving into the utilization of resorbable implants for osteosynthesis in pediatric cases. His research further expands our understanding of this evolving field, exploring possibilities for enhanced treatment modalities and improved patient outcomes. Furthermore, Mathis Wegner presents his insights into a minimally invasive orthosis designed to address a fixed equinus deformity following a modified transverse Vulpius procedure. This novel orthosis holds promise in rectifying this deformity while minimizing invasiveness, thus offering potential benefits to pediatric patients.These contributions to the knowledge of minimally invasive pediatric surgery collectively underscore the constant pursuit of innovative techniques and advancements aimed at optimizing patient care and improving long-term outcomes.This remarkable collection merits great attention, as it encompasses 27 pioneering works by surgeons who fearlessly expand the horizons of minimally invasive pediatric surgery.We thank all the contributors, and congratulate them on their excellent work.Best regards from Sankt Gallen, Switzerland and Kiel, Germany.Thomas Franz Krebs and Robert Bergholz.


Injection drug use using nonsterile equipment can lead to transmission of viral, bacterial, and fungal infections. Frontline healthcare workers (HCW) are at high risk for substance use disorder due to unprecedented job stress and access to injectable controlled substances. The Tennessee Department of Health (TDH) developed a collaborative investigative process to determine the risk of bloodborne pathogen (BBP) transmission from licensed HCWs engaging in drug diversion. This program recommends public health action and provides consultation to improve drug diversion programs.In 2019 TDH formed a drug diversion investigation team (DDIT) consisting of pharmacists, epidemiologists and medical directors from the HAI and HIV/STI/Viral Hepatitis programs. The DDIT responds to notification by the Health-Related Boards (HRB) of a licensed HCW under investigation for diversion of injectable products. The DDIT interviews the investigator and meets the facility drug diversion program to review drug diversion policies and processes. Based on the suspected method(s) and, if known, the individual’s Hepatitis B/C and HIV status, recommendations are made regarding the need for patient notification and testing.From 2020–2022 the DDIT received notification of 49 licensed HCWs under investigation for diversion of injectable products. Patient notification and testing was recommended in seven facilities for CDC Category A infection control breaches; in two cases, later HCW testing negated the need for further action. Among the 34 facilities queried, only five (14.7%) had existing policies for for-cause BBP testing. Other recommendations to improve diversion programs include infection prevention participation and releasing “not eligible for rehire” status to other facilities.The TDH DDIT facilitates communication with HRB on reported cases of injectable drug diversion. Joint investigations with facilities raise awareness of the risk of BBP transmission and improve facility diversion programs. Tennessee facilities are adding for-cause BBP testing to their investigation procedures. The TDH DDIT model receives mostly positive responses from facility and health system drug diversion teams and may be considered by other public health jurisdictions.All Authors: No reported disclosures


Breast cancer is the most common cancer worldwide, and advanced breast cancer with metastases is incurable mainly with currently available therapies. Therefore, it is essential to understand molecular characteristics during the progression of breast carcinogenesis. Here, we report a dataset of whole genomes from the human mammary epithelial cell system derived from a reduction mammoplasty specimen. This system comprises pre-stasis 184D cells, considered normal, and seven cell lines along cancer progression series that are immortalized or additionally acquired anchorage-independent growth. Our analysis of the whole-genome sequencing (WGS) data indicates that those seven cancer progression series cells have somatic mutations whose number ranges from 8,393 to 39,564  compared to 184D cells. These WGS data and our mutation analysis will provide helpful information to identify driver mutations and elucidate molecular mechanisms for breast carcinogenesis. They were clonally selected to yield seven HMEC lines ([Breast cancer is the most common cancer diagnosed among women in the United States (excluding skin cancers). It is the second leading cause of cancer death among women after lung cancer . It is cigenesis   to isolate gDNA from HMEC cultures. The quantity of the extracted gDNA was analyzed with an ND-1000 spectrophotometer . For WGS library construction, we used the TruSeq DNA library Prep Kit  according to the manufacturer’s instructions. For WGS, paired-end sequencing was performed on the Illumina HiSeq X Ten sequencing instrument, yielding ~150-bp short sequencing reads.Raw sequence reads were aligned to the human reference genome 19 using Burrows Wheelers Aligner , and duphttps://kobic.re.kr/kona) and Sequence Read Archive  public database with the accession number PRJKA220370 and PRJNA913438.The whole-genome data are available in the Korean Nucleotide Archive . Then, we performed the driver mutation analysis using the IntOGen cancer mutation browser  and obseIn this study, we generated WGS data and analyzed mutation profiles in the HMEC cancer progression series because genetic mutations are one of the most significant factors in determining breast cancer progression and therapeutic management . We hope


Rhinella marina) that is particularly successful in human-altered landscapes. There have been numerous investigations of the cane toad diet, but most of these studies identified prey items at lower taxonomic resolutions . We used higher resolution for prey identification and multiple dietary measures of prey consumption to assess the ecological role of cane toads in the urban landscape of southwest Florida. Prey taxa commonly considered urban pests dominated the diet of cane toads inhabiting golf course communities, and there were differences in prey consumed during the wet and dry seasons of this region. We provided a better understanding of the potential relationships between cane toads and their prey in the urban environment.Urban ecosystems provide habitat to many species, including invasive species such as the cane toad (Rhinella marina) inhabiting urbanized areas in southwest Florida to provide high taxonomic resolution of prey items, contrast toad diets between sampling seasons and sexes, and assess this invasive species’ ecological role in the urban landscape. A pest control agency collected cane toads from two golf course communities in Naples, Florida, USA during November–December 2018 (early dry season) and June–July 2019 (early wet season), and faunal stomach contents were quantified from a random subsample of 240 adult toads . Yellow-banded millipedes (Anadenobolus monilicornis), big-headed ants (Pheidole spp.), and hunting billbugs (Sphenophorus venatus vestitus) were the most frequently consumed prey items and had the highest total numbers and/or volume with corresponding highest indices of relative importance. There was considerable overlap in the seasonal prey importance values for each golf course community and little if any difference in the importance values between toad sexes in each community. Nonetheless, big-headed ants were the most important prey in both communities during the wet season, while yellow-banded millipedes were the most important dry season prey in one community and hunting billbugs the most important in the other. Despite limited spatiotemporal sampling effort, our results indicated that cane toad was consuming arthropod taxa considered pests in the urban ecosystem. Further studies are needed to investigate the potential effects of human activities and environmental variability on the cane toad diet and to determine whether cane toads act as a biological control for pest populations.We investigated the diet of cane toads ( Rhinella marina) is one such invasive species that has demonstrated an affinity to human habitation [Urban areas are often seen as ecologically inferior to their natural area counterparts; however, in the age of rapid urbanization, these developed areas have nonetheless become complex ecosystems inhabited by many species with their own adaptations to the novel urban conditions ,2. An adbitation ,10,11,12The cane toad is a large, toxic amphibian with a native range from southern Texas, USA and western Mexico, through Central America, and into central Brazil . This NeKnowledge of a species’ diet is crucial to understanding its interactions with other species and, in some cases, function in the urban ecosystems it may inhabit ,25. DextAnaxyrus terrestris). Rossi [There have been three diet studies for cane toads in Florida, all of which were conducted in urban ecosystems. Krakauer  characte). Rossi  focused The purpose of our study was to examine the dietary composition of cane toads inhabiting residential golf course communities in southwest Florida. The objectives were to provide fine-scale taxonomic resolution of prey items, contrast cane toad diets between sampling seasons and sexes, and assess this invasive species’ ecological role in the urban landscape.Our study was located in Naples, Collier County on the southwest coast of Florida, USA . Herein,A licensed pest control agency was contracted by the golf course communities to remove cane toads from their respective properties. Toads were collected by hand between 22:00 and 01:00 during November–December 2018 (early dry season) and June–July 2019 (early wet season). Captured toads were kept in ventilated buckets and later euthanized via cooling then freezing . We selet-test.For toad sexes, differences in SUL between seasonal collections in the golf course communities were analyzed with Welch’s ANOVA and Games–Howell post hoc tests using the Real Statistics Data Analysis Tools add-in  for MicrPercent frequency of occurrence (%F), number (%N), and volume (%V) of cane toad prey taxa were determined byi with equationA percent index of relative importance  was calCompound indices such as IRI reduce potential bias associated with the component diet measures ,53. ExamMultivariate analyses were performed on cane toad dietary compositions using PRIMER v6 software . AmbiguoR is an absolute measure of the separation between two or more groups, typically ranging between 0 (no separation of groups) and 1  was used to contrast diet composition between sampling seasons, allowing for differences between toad sexes, and between sexes allowing for differences between seasons. The ANOSIM statistic aration; ). Unlikeificant; ). Two-wap = 0.002) among seasonal sampling events with smaller females collected during the early dry season in golf course Community A , big-headed ants (Pheidole spp.), and hunting billbugs (Sphenophorus venatus vestitus) were the most frequently consumed prey items and had the highest total numbers and/or volume with corresponding highest indices of relative importance (combined IRI of 74%) for all taxonomic categories.A total of 13,961 prey items in 180 taxonomic categories  was identified from the stomachs of 239 cane toads . One of Labidura riparia) were also frequently consumed (62% F) during this season, but their lower contributions to prey volume and number resulted in lower relative importance (16% IRI). In contrast, yellow-banded millipedes were the dominant dry season prey  in golf course Community B with much lower contributions to the diet measures by hunting billbugs and a corresponding low relative importance (7% IRI). Big-headed ants were the most important early wet season prey in both golf course communities (49% IRI), owing to the high frequency of occurrence and the highest contributions to number of prey items but with relatively low-volume contributions. Yellow-banded millipedes in both communities and lepidopterans, primarily caterpillars, in Community B were also frequently consumed during the wet season and both taxa had the highest prey volume contributions but much lower numbers and corresponding relative importance. Additionally, Cuban May beetles (Phyllophaga bruneri) and scavenger scarab beetles (Hybosorus illigeri) were only consumed during the wet season in both communities.After resolving ambiguous taxonomic categories, there were 109 unique prey taxa , and 14 of these unambiguous taxa had an IRI > 1% for at least one of the seasonal cane toad collections in either of the golf course communities  in prey importance value percentages between sampling seasons. The low R value indicated moderate overlap with some separation in prey compositions. The SIMPER routine identified hunting billbugs as contributing the most to the seasonal diet dissimilarity in Community A with a much greater mean importance value percentage for this prey item in the early dry season (Camponotus floridanus) had higher mean percentages during the early wet season. Other distinctive prey items only consumed in the wet season included uneven billbugs  and Cuban May beetles. The average similarity value for prey taxa consumed in the early dry season (26.4%) was higher than that of the early wet season (18.9%), but these relatively low similarity values also indicate considerable variability in prey consumed by toads during each season.For golf course Community A, there was a significant difference  in prey importance value percentages between toad sexes in golf course Community A; however, the very low R value indicated strongly overlapping importance value compositions with little difference between sexes. Nonetheless, hunting billbugs were identified by the SIMPER routine as contributing the most to the dietary dissimilarity between toad sexes and males exhibited a greater mean Importance value percentage for this prey item  in prey importance value percentages between sampling seasons and the low R value indicated moderate overlap with some differences in prey compositions. The SIMPER routine identified yellow-banded millipedes as contributing the most to the seasonal dissimilarity in Community B and this prey item had a substantially greater mean importance value percentage during the early dry season (Asiomorpha coarctata), and shore earwigs also had higher importance value percentages during the early dry season but contributed less to the seasonal dissimilarity. Big-headed ants and lepidopterans had higher mean importance value percentages during the early wet season. Other prey items with distinctive wet season differences included Cuban May beetles, scavenger scarab beetles, darkling beetles (Platydema), and rover ants (Brachymyrmex). Average similarities were higher in the early dry season (23.5%) compared to the early wet season (11.5%), but dietary variability was indicated by the relatively low values.For golf course Community B, there was a significant difference  in prey importance value percentages between toad sexes in golf course Community B. The negligible R value indicated dietary compositions were barely separable with little if any differences in prey importance values between sexes. Furthermore, the borderline statistical significance should be interpreted cautiously owing to the relatively high number of replicates/permutations and their influence on significance levels. The SIMPER routine indicated some minor dietary differences by sex . Ideally, dietary investigations should employ at least one metric measuring amount (frequency and number), and one measuring the bulk of food items present in each sample [In addition to prey resolution, the choice of diet metrics may have influenced previous interpretations of cane toad diet. Most studies reported one or two diet metrics for prey taxa, such as frequency and/or number, and only a few measured the bulk (volume or mass) of food items . Only Pah sample . Reportih sample . As demoDespite individual variability and overlapping dietary compositions, cane toads exhibited significant seasonal differences in prey consumption in southwest Florida. Big-headed ants were the most important prey in both golf course communities during the early wet season and contributed the most to the differences for this season in both communities. Florida carpenter ants were also important wet-season prey in Community A. For regions with seasonal patterns of precipitation, cane toads ingested higher numbers of ants during the wet season in a coastal village of the Philippines  and withPrey compositions during the early dry season differed significantly from those in the early wet season for both golf course communities, but the importance of dry-season prey types also differed between communities. Hunting billbugs were the most important dry-season prey in Community A, while yellow-banded millipedes were more important in Community B, and both prey items contributed the most to the seasonal differences in the respective communities. The golf course communities in our study were relatively proximal to one another  so location does not appear to be a factor; however, different human activities may be affecting arthropod ecology, or our perception as such, within each community . HuntingYellow-banded millipedes, hunting billbug weevils, and bigheaded ants were the most important prey items for cane toads collected from golf course communities in southwest Florida. These arthropods are considered urban pests, but further studies are needed to determine whether cane toads provide any beneficial service with respect to the consumption of these nuisance taxa in the urban ecosystem. Our higher resolution for prey identification provided a better understanding of potential predator–prey relationships and their inferred use of habitats in the anthropogenically altered landscape. Furthermore, using multiple dietary metrics revealed size bias with the prey , and applying compound indices provided a balance for interpretations of prey importance. There were significant seasonal differences in prey importance for cane toads, possibly related to the behavior of toads and the ants consumed during the wet season, and a locational difference in dry season prey importance that could have resulted from pest management practices in the golf course communities or unintentional bias during toad collections. We recognize the limited spatiotemporal scope of sampling effort in the current study and suggest a more rigorous, multiannual sampling design to address the potential effects of human activities and environmental variability on cane toad diet in urban ecosystems.


Wound healing is a complex and coordinated biological process easily influenced by various internal and external factors. Hydrogels have immense practical importance in wound nursing because of their environmental moisturising, pain-relieving, and cooling effects. As photo-crosslinkable biomaterials, gelatine methacryloyl (GelMA) hydrogels exhibit substantial potential for tissue repair and reconstruction because of their tunable and beneficial properties. GelMA hydrogels have been extensively investigated as scaffolds for cell growth and drug release in various biomedical applications. They also hold great significance in wound healing because of their similarity to the components of the extracellular matrix of the skin and their favourable physicochemical properties. These hydrogels can promote wound healing and tissue remodelling by reducing inflammation, facilitating vascularisation, and supporting cell growth. In this study, we reviewed the applications of GelMA hydrogels in wound healing, including skin tissue engineering, wound dressing, and transdermal drug delivery. We aim to inspire further exploration of their potential for wound healing. The skin is a multifunctional barrier organ that protects internal organs from potential environmental hazards . The proGelMA is a synthesised biomacromolecule with excellent biocompatibility and formability; it was first reported to be synthesised by Bulcke et al., in 2000 . Since tin situ photo-crosslinking properties make GelMA hydrogels particularly suitable for application in irregular wounds  and hydroxyl (–OH) groups on the side chains of gelatine are substituted by the methylacryloyl group . GelMA-dHAMMA hydrogels were found to promote fibroblast proliferation and α-smooth muscle actin expression. GelMA-dHAMMA has also been shown to promote wound collagen deposition and angiogenesis and accelerate tissue healing in rabbit full-thickness skin tissue defects  are competitive candidates because of their excellent biological characteristics .in vivo vascularisation. In a previous study, epidermal stem cell–derived EVs loaded with VH298 were encapsulated in GelMA hydrogels to enhance the angiogenic ability of diabetic wounds. GelMA hydrogels were shown to be convenient and adaptable delivery carriers for the sustained release of VH298-EVs, effectively promoting wound healing by locally improving blood supply and angiogenesis by increasing the HIF-1a level  delivery (Microneedles are one of the transdermal drug delivery techniques that usually release loaded drugs directly into the deep layer of the skin through tiny holes formed by puncture . Hydrogedelivery . The micIn conclusion, GelMA hydrogels have been widely used in many applications, ranging from wound dressings to 3D printing skin tissue engineering. They provide an ideal multistratified anisotropic scaffold for the growth of various cells such as fibroblasts, endothelial cells, and keratinocytes. They can also be used to prepare personalised multifunctional dressings by combining small molecules, metal nanoparticles, and cellular EVs via physical binding or chemical reactions. Therefore, the application prospects of GelMA hydrogels for wound healing are significant. However, the biosafety of GelMA-based hydrogels remains a major obstacle to their clinical applications. The release of unreacted methacryloyl monomers after photo-crosslinking is a potential risk. Furthermore, photo-crosslinking under UV radiation may damage cellular DNA . Additio


Impairments in cognitive and executive function of presumed cerebral microvascular origin are important and recently recognized neuropathological manifestations of vascular contributions to cognitive impairment and dementia (VCID) , 2. It hStudying WM continues to pose unique methodological and diagnostic challenges for aging research. WM is highly enriched in auto-fluorescent pigments that make rigorous immunohistochemical (IHC) approaches for mechanistic and diagnostic studies extremely challenging. Although astrocytes may degenerate in overt WM infarcts, the vulnerable glial subtypes in diffuse microvascular WM lesions remain essentially unknown. Admittedly, glial lineages are complex and relatively few specific markers are available. Furthermore, the expression of glial markers can change dramatically in regions of WM injury leading to nonspecific false positive staining . In addiTo provide rigorous access to human WM lesions, we recently developed a unique rapid autopsy brain procurement protocol using specimens donated by participants in the Adult Changes in Thought (ACT) study, a prospective, population-based study of aging and incident dementia among men and women in Seattle, Washington . This prA unique opportunity afforded by this rapid autopsy brain procurement protocol is access to fresh tissue samples for direct analysis of human penetrating microvessels. We have developed novel protocols to preserve these vessels for a wide range of physiological and molecular studies performed within 24 hours after procurement. Although cerebral microvascular disease is a common manifestation of aging, prior human and murine vascular and morphological studies were limited mostly to the middle cerebral artery and pial microvessels, and findings were extrapolated to WM penetrating microvessels. Moreover, despite growing interest in WM injury and MRI-defined WM hyperintensities in VCID and AD, vascular studies mostly lacked histopathological, neuroimaging or mechanistic correlation.We established the feasibility to study human penetrating WM arterioles in initial studies of aged human microvascular lesions with low ADNC . We founThe molecular mechanisms that mediate enhanced dysfunction of WM parenchymal arterioles when vascular dysfunction and ADNC coincide remain elusive. Analysis of human WM lesions and WM parenchymal arterioles , 7, as wTaken together WM injury and WM hyperintensities of presumed microvascular origin are of growing interest to aging and VCID researchers. A growing body of evidence supports that microvascular brain injury is accompanied by oxidative stress, astrogliosis, changes in the extracellular matrix , and quantitative MRI-defined abnormalities in prefrontal WM that involve disrupted integrity of axons and myelin. Mechanistic studies are needed to further define contributions of microvascular dysfunction to WM injury, particularly as it relates to the identities of the cell types and molecular signatures that could be harnessed to diagnostically discriminate among VCID, AD or mixed vascular/ADNC.


Cancer is the second most common fatal disease leading to death worldwide. Metastatic growth in distant organs is the main reason for increased cancer mortality . Cancer in vivo mouse models targeting cancer stem cells and their signaling pathways  which are effective in treating pancreatic cancer. The article focuses on the mode of action of bioactive plant metabolites from TCM against various signaling pathways such as Wnt and Notch, which regulate cancer stem cells in pancreatic cancer. Zhang et al. explain the inhibition of cancer stem cell signaling pathways involved in epithelial to mesenchymal transition, migration, metastasis and apoptosis of pancreatic cancer cells by the plant metabolites.The exploration of plant derived drugs as potential therapeutic interventions against cancer stem cells and metastasis is an exciting area of research that complement existing cancer therapies and improve patient outcomes. Koklesova et al. describes how nanoparticles specifically designed to target cancer stem cells in tumor, serve as carriers for targeted delivery of plant-based drugs. Several Nano-drugs developed to target and treat the different types of cancer and their subsequent CSCs are discussed. Plant metabolite-based nanoparticles are modified to specifically target cancer stem cells, which helps in reducing the risk of tumor recurrence and the manifestation of metastases. Zhao et al. describe the anti-metastatic effect of thymoquinone in pancreatic cancer and its sensitivity to gemcitabine by regulating collagen. In pancreatic cancer cells, thymoquinone promotes apoptosis, inhibits tumor cell migration, invasion and metastasis, and sensitizes pancreatic cancer cells to gemcitabine. Furthermore, the study shows that thymoquinone stimulates cellular matrix production via TGFβ/Smad pathways.Targeted therapies for the heterogeneous population of cancer tumors and multidrug resistance associated with cancer stem cells are still not effectively established. The review article by Mazurakova et al.). In the systemic review article, Mazurakova et al. detail the effect of flavonoids on breast cancer stem cells to combat therapy resistance and cancer proliferation. The accumulation of breast cancer stem cells (BCSCs) after chemotherapy, prevents further effective treatment of breast cancer patients. Therefore, it is also postulated that eradication of BCSCs in combination with standard cytotoxic drugs and flavonoids specifically targeting CSCs in breast cancer tumor is essential for successful treatment.Studies show that flavonoids have an anticancer effect against various types of cancer. Flavonoids can induce apoptosis and autophagic cell death of breast cancer cells, inhibit cancer proliferation and overcome drug resistance of cancer tumors (This Research Topic provides new data and detailed reviews on plant-derived compounds that target cancer stem cells and inhibit metastasis through various mechanisms of action by modulating self-renewal pathways, suppressing EMT, affecting the tumor microenvironment and disrupting signaling pathways essential for cancer cell migration, invasion and survival. Thus, plant metabolites are promising for developing innovative therapeutic strategies against cancer stem cells and metastasis. Prospective research is inevitable to successfully translate research findings into clinical trials by addressing challenges such as safety, bioavailability, formulation and standardization of herbal medicines. These findings and reviews demonstrate how phytomedicines targeting cancer stem cells significantly reduce metastasis and subsequent mortality. These prospective and innovative findings, if clinically established, are promising and can pave the way to new vistas for cancer therapy.


Advances and Challenges of Non-Invasive Brain Stimulation in Age-Related Neurodegenerative Diseases”, highlighting the significance of aging as a risk factor for neurodegenerative diseases, the limited effectiveness of current treatments and the potential of non-invasive brain stimulation.This editorial summarizes the contributions of the Frontiers Research Topic “Aging is a major risk factor for neurodegenerative diseases. Neuronal losses during aging can lead to cognitive decline, particularly when combined with accumulation of toxic proteins. Treatment options for these conditions are limited. Noninvasive brain stimulation (NiBS) techniques, such as transcranial magnetic stimulation (TMS) and transcranial current stimulation (TCS), can modulate brain networks and enhance cognitive functions in both healthy individuals and neurodegenerative patients. The effects of NiBS can persist even after the stimulation ends. However, a comprehensive understanding of its biological mechanisms and clinical applications is still lacking, which poses challenges. This topic aims to explore NiBS as an innovative therapeutic tool, specifically discussing its advances and challenges in treating age-related neurodegeneration.He et al. promoted that spinal cord stimulation (SCS) is a promising treatment for disorders of consciousness (DoC). This study analyzed 66 DoC patients who received SCS treatment to investigate the association between postoperative cerebrospinal fluid (CSF) protein levels and consciousness improvement. Patients with permanent electrodes had higher CSF protein levels than those with temporary percutaneous electrodes. Moreover, elevated CSF protein levels were linked to reduced sagittal diameter and poor outcomes at 3 months. The findings propose that reducing the influence of electrode pads on anatomical changes may improve treatment outcomes. CSF protein levels could serve as potential biomarkers of postoperative outcomes and deserve further exploration.A study conducted by Ni et al.) evaluated the effects of various repetitive TMS (rTMS) stimulation procedures on upper limb function and brain functional network characteristics in stroke patients. The study involved 36 stroke patients who were assigned to either receive 1 Hz stimulation in the contralesional hemisphere and 10 Hz stimulation in the affected hemisphere, or solely 10 Hz stimulation in the affected hemisphere. The results demonstrated that rTMS treatment improved upper limb motor function, enhanced brain network connections, and reduced activation of isolated brain areas. Depending on the specific brain network states, optimal rTMS treatment plans could be suggested for precise rehabilitation.Another study  explores the effects of continuous theta burst stimulation (cTBS) on enhancing language abilities in patients with aphasia. The researchers focused on targeting the right posterior superior temporal gyrus (pSTG), a region acknowledged for its critical role in semantic processing. This article presents findings from a randomized controlled trial involving 34 aphasic patients who underwent either cTBS or sham stimulation, followed by speech and language therapy. The study aimed to uncover whether cTBS applied to the right pSTG could promote language recovery and elucidate the underlying brain mechanisms. The results showed promising effects of cTBS, manifesting as improved language performance and modulation of brain activity and connectivity in specific regions. Overall, this research offers valuable insights into potential therapeutic interventions for language rehabilitation in individuals with aphasia.Another study  investigates the effects of brain stimulation on two different age groups: middle-aged adults (40–60 years) and older adults (65 years and above). The researchers aimed to understand how tDCS impacts behavior and brain function differently in these two groups. Additionally, behavioral assessments and neurophysiological measurements were performed. This research provides valuable insights into age-specific brain stimulation effects and its potential applications for cognitive enhancement.One article  explores the potential therapeutic effects of two brain stimulation techniques, median nerve stimulation (MNS) and rTMS, on patients with prolonged disorders of consciousness (pDOC). In a rigorously conducted trial, 75 eligible patients with pDOC were randomly assigned to one of three groups: (1) rTMS + sham-MNS; (2) MNS + sham-rTMS; or (3) MNS + rTMS. The primary outcome was the change in the Coma Recovery Scale-Revised (CRS-R) score after treatment. Findings showed that the combined MNS + rTMS intervention yielded significantly greater improvements in Glasgow Coma Scale (GCS) scores and somatosensory evoked potentials, compared to the other two groups. This research offers valuable insights into the potential benefits of combining brain stimulation modalities to enhance consciousness recovery in patients with pDOC.Another article  and elderly adults (65–80 years). They aimed to measure the impact of stimulation on motor skills and cortex responsiveness. The study revealed significant age-related differences, indicating that ccPAS enhances action performance and corticomotor excitability more effectively in young adults compared to elderly adults. These findings offer valuable insights into the age-specific effects of brain stimulation and its potential applications for cognitive enhancement. By delving into this research, the researcher can gain deeper understanding of how brain stimulation techniques may differ in their outcomes based on age, contributing to advancements in neurostimulation and its implications for age-related cognitive functions.In a study conducted by Naparstek et al.) presents a comprehensive review of the potential uses of transcutaneous vagus nerve stimulation (tVNS), a non-invasive neuromodulation technique, in the context of cognitive aging. The authors have compiled a thorough review and provided valuable commentary on the existing literature, shedding light on the effectiveness of tVNS in enhancing various cognitive functions in older adults. Through this review, researchers can uncover the promising applications of tVNS for memory, attention, and executive functions in the aging population. This review not only synthesizes the current knowledge on tVNS but also suggests pathways for future research, offering new insights into innovative therapeutic approaches for addressing age-related cognitive decline.Another study (YG: Writing—original draft. WW: Writing—review and editing. JZ: Writing—review and editing.


This cross-sectional study compares clinician and artificial intelligence (AI) chatbot responses to patient vignettes used to identify bias in medical decisions. This study aimed to evaluate AI chatbot responses to clinical questions previously tested in large samples of clinicians to examine established biases in medicine related to gender, race and ethnicity, and socioeconomic status (SES) through published vignettes.Artificial intelligence (AI) chatbots transformed how we access information provided by large language models. However, AI models may carry inherent bias, often mirroring the systematic inequalities present in our society.STROBE) reporting guideline. This study was deemed exempt from the institutional review board at Stanford University. Informed consent was waived because the study did not involve human participants. We selected 19 clinical vignettes in cardiology, emergency medicine, rheumatology, and dermatology. A full list of references can be found in the eReferences in This cross-sectional study followed the Strengthening the Reporting of Observational Studies in Epidemiology (The 4In this cross-sectional study, we observed that AI chatbots provided different recommendations based on a patient’s gender, race and ethnicity, and SES in certain clinical scenarios. We found both overlapping and unique differences in responses among the AI chatbots and between the AI chatbots and physicians. The presence of bias among clinicians and clinical risk algorithms has historically caused disparities in clinical care and led to poorer health outcomes for some marginalized populations. While AI chatbots have shown proficiency in various medical tasks, including passing the United States Medical Licensing Examination, interpreting laboratory tests, and answering patient questions, neither chatbot is approved for medical applications.5 Differences in AI chatbot recommendations have not been fully explored, and their impact is unclear. These differences may be shown to propagate or counter biases that clinicians have, the impact of AI-based tools on health disparities may vary in different clinical situations. However, these tools are being adopted by patients and clinicians, making further research especially urgent.Limitations include a small number of vignettes tested and different assessment scales used per vignette following the original studies’ approaches. Although AI chatbots are promising tools in medicine, our findings underscore the need for careful application of early adoption. Prior studies have suggested that using AI in medicine could contribute to treatment inequities in marginalized racial and ethnic groups.


Endoscopic ultrasound (EUS) has entered its golden age. The benefits of providing refined diagnosis and advanced therapeutic procedures by EUS are numerous and widely appreciated by clinicians worldwide –3.Just 20 years ago, EUS diagnosis was based mainly on radial mechanical echoendoscopes with no electronic image enhancement functions . On the Since then, EUS has gone through years of exciting and unrelenting scientific and technologic advancements. The biggest improvements were introduced by image enhancement techniques with ultrasound contrast agents and elastography allowing better detection and characterization of the lesions of interest.Frontiers in Medicine about advancements in the EUS diagnosis of pancreatobiliary diseases, image enhanced EUS for the diagnosis of gallbladder lesions is presented. Differential diagnosis between benign and malignant gallbladder tumors can be challenging in order to select the candidates for surgery. Contrast-enhanced harmonic EUS (CH-EUS) has been previously reported to be useful for the diagnosis of gallbladder tumors  and accuracy (90%) . Data inThe usefulness of liquid-based cytology to increase the diagnostic yield of EUS-guided tissue acquisition is also discussed. Several techniques have been used in this regard, including fine needle biopsy with histology needles, rapid onsite cytopathology evaluation, and guidance by CH-EUS. A recent meta-analysis showed a pooled diagnostic sensitivity of 85% with CH-EUS-fine needle aspiration and 75% with standard EUS- fine needle aspiration . HoweverEUS is also a great tool for pancreatic cancer screening in conjunction with magnetic resonance imaging . InteresFinally yet importantly, bibliometric analysis of EUS publications is presented. Compared to previous EUS literature scans , an updaPF wrote the editorial. MT and YY reviewed the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.


They validated their initial findings by targeted metabolomic analyses in two different cohorts with similarly increased cardiovascular risk, from the United States (n = 2149) and Europe (n = 833) undergoing cardiac evaluation. This follow-up analysis strengthened their original findings by revealing that the association of erythritol not only remained significant but was independent of age, sex, and other established risk factors. This suggests the additional operation of other than metabolic mechanisms. Indeed both in vitro and in vivo studies in human whole blood and mice revealed an erythritol-elicited increase in platelet adhesion and clot formation (Fig. 1 Their subsequent pilot study showed that a single dose of 30 g erythritol results in prolonged excessive plasma erythritol elevation for over 48 h. The recorded concentrations remained well above the threshold, which increased platelet reactivity and thrombocyte reactivity in vitro,1 suggesting a prolonged thrombotic risk arising from exogenous erythritol.Abnormal vascular function and coagulation represent other central drivers of cardiovascular disease onset and development.3 At present, controlled trials did not detect detrimental effects of erythritol ingestion in healthy humans,5 but specific trials on vascular function and coagulation in healthy and diseased humans are lacking.While these studies support a novel conceptual framework of erythritol-induced promotion of thrombus formation leading to excess cardiovascular risk, several limitations need to be addressed. There is not only a lack of standardization of erythritol measurements but also of the preanalytical conditions. The observed prolonged elevation of erythritol upon dietary intake raises the question of whether simple overnight fasting conditions suffice for the interpretation of baseline concentrations; moreover, the kinetics of erythritol elimination might substantially differ between healthy and metabolically compromised people. Importantly, their in vitro procedures raised the platelet concentrations creating artificial experimental conditions. Also, the mice experiments showing enhanced clot formation upon erythritol injection do not necessarily mirror thrombosis risk in humans. Thus, a direct analysis of platelet activation in humans upon erythritol might better reflect real-life conditions. Further questions arise: to what extent do different conditions affect the relative contributions of exogenous versus endogenous sources to the total circulating erythritol concentration, particularly could people with increased cardiovascular risk produce more erythritol? One might speculate that altered hepatic metabolism in humans with type 2 diabetes, who are at higher risk of fatty liver disease, might at least contribute to the described effects. Of note, epidemiological and cohort studies cannot exclude reverse causality because people with an unfavorable metabolic profile are more prone to consume sugar-free meals to avoid weight gain or hyperglycemia, even before cardiovascular disease diagnosis.Taken together, Witkowski and colleagues shed light on one of the widely-used non-nutritive sweeteners and provide novel evidence for the potentially deleterious effects of erythritol on platelet function. At the same time, these findings raise new questions calling for sufficiently powered double-blind, randomized controlled trials addressing the safety as well as mechanistic studies examining the Janus-head-like features of erythritol. Importantly, the evidence derived from the current study should already suffice for the authorities to re-evaluate their policy statements regarding the cardiovascular and metabolic risks of artificial sweeteners.


Advanced Materials (2023) 10.1002/adma.202306834Owing to the absence of appropriate helical templates, circularly polarized organic ultralong room temperature phosphorescence with a high dissymmetry factor remains a formidable challenge in contemporary research. A team of Qiang Zhao and Yanqing Lu proposes an effective tactic to enable the high dissymmetry factor by employing a circularly polarized phosphorescent system composed of meticulously designed phosphorescent polymers and self-assembled chiral helical superstructures. Specifically, multiple interactions among polymer chains can strictly restrict molecular motions of phosphorescent molecules, thereby inhibiting the non-radiative relaxation pathways and resulting in the emission decay time of 735 ms. The self-organized periodic helical superstructures serve as an ideal medium for enhancing chirality, giving rise to the attained dissymmetry factor of 1.49 and surpassing previous records by two orders of magnitude. The creatively explored system displays remarkable photo-thermal stability and demonstrates the potential applications of photoprogramming photonics. These findings would create a brilliant outlook of the optical multiplexing-based information encryption, and establish the intimate connection between circularly polarized phosphorescent materials and the evolving field of optical information technologies toward the cutting-edge photonic applications and beyond.


Popular press coverage of the Medicare Part D coverage gap is based largely on research conducted using retrospective analyses of administrative claims data. These datasets are incomplete because they lack information about methods of obtaining medication that are commonly used by seniors, including free samples, generic drug discount programs, over-the-counter substitution, and patient assistance programs. As a result, evidence about the effects of 100% cost sharing on seniors is limited and suboptimal. Although the current deficit of information about the coverage gap is not entirely unexpected because the Medicare Part D program is relatively new, reliance on claims-based analyses to inform questions that claims data cannot possibly address accurately has tended to mislead and politicize rather than produce constructive policy guidance. Numerous important health policy questions remain unaddressed. These questions are becoming especially important as optimal approaches to providing health care to seniors are the subject of an increasingly vigorous debate.


Parents frequently purchase and inquire about smartwatch devices to monitor child behaviors and functioning. This pilot study examined the feasibility and accuracy of using smartwatch monitoring for the prediction of disruptive behaviors.N = 10) aged 7–10 years hospitalized for the treatment of disruptive behaviors. The study team completed continuous behavioral phenotyping during study participation. The machine learning protocol examined severe behavioral outbursts  for preparing the training data. Supervised machine learning methods were trained with cross-validation to predict three behavior states—calm, playful, and disruptive.The study enrolled children (The participants had a 90% adherence rate for per protocol smartwatch use. Decision trees derived conditional dependencies of heart rate, sleep, and motor activity to predict behavior. A cross-validation demonstrated 80.89% accuracy of predicting the child's behavior state using these conditional dependencies.This study demonstrated the feasibility of 7-day continuous smartwatch monitoring for children with severe disruptive behaviors. A machine learning approach characterized predictive biomarkers of impending disruptive behaviors. Future validation studies will examine smartwatch physiological biomarkers to enhance behavioral interventions, increase parental engagement in treatment, and demonstrate target engagement in clinical trials of pharmacological agents for young children. Evidence-based interventions such as parent–child interaction therapy (PCIT) reduce behavioral and emotional symptoms in children by improving parent–child relationships through the implementation of specific rules taught over a multiweek period  the effectiveness of PCIT is contingent upon parents making a concerted effort to remember the rules imparted by a provider in engaging with their children and (2) families from rural areas and under-represented populations are less likely to have access to and utilize evidence-based therapies when it is available , there is an opportunity to improve access and effectiveness of behavioral interventions in children and adolescents, including PCIT. Smartwatches measure individual functioning in real time and provide opportunities to identify point-of-care smartwatch biomarkers in young children that can provide prompts for parents of child's impending behavioral outbursts. Accessible digital tools may have the promise of increasing parental engagement for improved outcomes.The growth in children's smartwatch market  is largely driven by parental interest to track their child's functioning  aged 7–10 years were enrolled in this IRB-approved study conducted during May 2020 through December 2020. Registered nurses (RNs) of the Mayo Clinic Child and Adolescent Psychiatry inpatient unit continuously assessed and annotated behavior for 24 hours daily during hospitalization , heart rate (beats per minute), and sleep (including duration and sequence of sleep stages) data through the Garmin Connect mobile application. The smartwatch minute-level data were aggregated and collected through Fitabase. Each participant and family had an abbreviated PCIT training intervention during hospitalization.Calm  indicated that the child was sedentary while performing routine activities such as reading, lying down, watching movie, talking/interacting with others, or doing their daily homework. Playful  indicated that the child was engaged in a nondisruptive activity of elevated heart rate such as exercising , playing a sport , or playing with other children .Inpatient RNs annotated behavior states as either calm, playful, or disruptive using the behavior code described in Disruptive (behavior codes 9–11) indicated that the child showed uncontrolled aggression/behavior  warranting intensive behavioral interventions, time-outs, or restraint for safety. For each of the calm, playful, and disruptive phenotypic annotations on a given day, the corresponding average heart rate in the preceding 60 minutes and the durations of sleep stages from the previous night were captured with the smartwatches (see ches see .Decision trees were trained to use heart rate (60-minute average) and sleep data to predict calm, playful, or impending disruptive behaviors  across the three behavior phenotypes. The Garmin vivosmart4 smartwatch provides three levels of intensity of motor activity . Notably, when participants were characterized as calm, there was no difference (p > 0.8) between the mean heart rate during the 60-minute calm period and the overall resting heart rate . However, the durations of REM, light, and deep sleep stages were different between participants who exhibited disruptive behavior versus those who did not  if the duration of light sleep exceeded 4 hours, and there were no significant associations with the total sleep duration or duration of awake, deep, and REM sleep.The Garmin vivosmart4 watch provides the duration and sequence of sleep stages   with an accuracy of 80.89%.Prior research has demonstrated parental acceptance -approved features  are becoming ubiquitous across all ages for wellness monitoring and improved health-related outcomes. Cardiology practice has adopted the use of smartwatch devices for monitoring and assessment of remote cardiac monitoring  are underway to establish benchmarks and the utility of wearable devices for monitoring, decision support, augmented interventions, and predictive models. Valid and accessible digital biomarkers will have great utility for future pharmacological trials for young children.This study has limitations. First, an inpatient monitoring study did not present specific behavioral triggers in outpatient settings . Biomarker thresholds and accuracies of predicted behavior states may vary between patients based on parents' perception of what constitutes disruptive behavior versus nearly homogeneous annotations of disruptive behavior marked by trained nurses. Second, only one smartwatch brand was used and additional studies with trackers from other vendors  are needed. Third, the study used data from hours with complete measurements, hence the impact of time gaps in measurements is yet to be understood.Fourth, it is possible that more computationally intensive algorithms may outperform prediction performance of decision trees with larger sample sizes and duration of observation. Fifth, although the study psychiatrists and medical records did not identify any medication-related side effects in the sample, the potential impact of concurrent psychotropic medications on physiological measures (including sleep disturbances) is unknown as it is highly possible that the threshold of biomarkers varies with time and improves behavior states.Therefore, larger studies with longer duration of observation and treatment modalities are needed to further develop and refine time-series algorithms to predict impending disruptive behavior in children. Finally, digital biomarkers derived in this study need validation in an outpatient setting to guide the development of a technology-enhanced version of behavioral interventions such as PCIT.There is a critical societal need to better understand and leverage scalable remote technologies to foster healthy parenting practices within the framework of traditional evidence-based behavioral therapies such as PCIT. This feasibility study demonstrates the capability to introduce precision target-based  technologies using smartwatch-derived biomarkers to improve effectiveness of psychosocial interventions in young children by predicting disruptive behavior in children before manifestation. Such biomarkers when successful could be utilized in delivering precision care to children and families through remote care capabilities—thereby addressing barriers to accessing specialty pediatric behavior clinics.


Acculturation refers to the process of change that occurs when people of different cultural backgrounds are in enduring first-hand contact  intersect to impact acculturation experiences in educational settings.While some papers focus on specific demographic groups, there is room for more research that considers Longitudinal studies could provide insights into how acculturation attitudes and experiences evolve over time, especially in relation to educational outcomes.Most of the papers employ cross-sectional designs. Comparative studies could provide insights into how cultural and national contexts influence acculturation processes in education.The papers focus on various geographical contexts. how educational policies impact acculturation processes. Future research could explore the role of policies in facilitating or hindering acculturation in schools.While the papers discuss individual and group experiences, there is a gap in the examination of technology in acculturation within educational settings remains underexplored. Research could focus on how digital platforms and online education impact acculturation experiences.In an increasingly digital world, the role of In summary, while the current Research Topic provides valuable insights into the relationship between acculturation and education, it also opens up multiple avenues for further exploration. These new directions could significantly enrich the academic discourse and have practical implications for educators, policymakers, and researchers alike.EM: Conceptualization, Writing—original draft. NL: Writing—review & editing. CW: Writing—review & editing. DB: Writing—review & editing.


Behavioral  and emotional  problems were showed to be associated with the prenatal environment. Changes in placental DNA methylation was identified as a relevant potential mechanism of such association.We aimed to explore the associations between placental DNA methylation and child behavior in order to explore pathways that could link prenatal exposures to child behavior.Data including 441 children of 3 years of age from the EDEN mother-child cohort. Child behavior assessed using the Strengths and Difficulties Questionnaire (SDQ). Both hypotheses-driven and exploratory analyses (including epigenome-wide association studies (EWAS) and differentially methylated regions (DMR) analyses) were conducted. The analyses were adjusted for confounding and technical factors and estimated placental cell composition. All the p-values were corrected using a false discovery rate (FDR) procedure for multiple tests.cg26703534 (AHRR), was significantly associated with emotional problems (pFDR = 0.03). In the exploratory analyses, cg09126090 (pFDR = 0.04) and cg10305789  were significantly associated with peer-relationship problems and 33 DMRs were significantly associated with at least one of the SDQ subscales. Placental DNA methylation showed more associations with internalizing than externalizing symptoms, especially among girls. DMRs tented to include highly methylated CpGs.In the hypothesis-driven analysis, This study investigated for the first time the associations between placental DNA methylation and internalizing and externalizing symptoms in preschoolers. Further analyses, such as consortium meta-analyses would be necessary to confirm and extend our results.None Declared


This could be due to the primary surgical oncologist informed by MD-PALS members being able to better identify key EOL issues surrounding the patient and hence better equipped to conduct a quality GOC discussion during a surgical admission.We established a multidisciplinary palliative surgical intervention (MD-PALS) team comprising healthcare providers of various subspecialties involved in the care of these patients. We then performed a single-centre prospective cohort study recruiting advanced cancer patients who received palliative interventions, comparing the outcomes of those cared for under the newly established MD-PALS team and those who received usual care.6 Future research should delve deeper into investigating and validating the other potential benefits of MD-PALS teams. Robust and rigorous studies will be essential in refining team structures and processes, ensuring the model is optimized to cater to the unique needs of palliative surgical oncology patients.Our study highlights the positive impact of multidisciplinary specialist providers’ involvement in the care of palliative surgical oncology patients, leading to enhanced GOC discussions. MD-PALS teams hold the potential to become the cornerstone of a ‘Community of Practice’, fostering interdisciplinary collaboration and seamless communication between team members, patients, and their families, ensuring the comprehensive and holistic management of the multifaceted challenges faced by these patients.


This editorial reports from seven international working groups from the US and Europe as follow-up of the Eight Kraepelin Symposium in Munich, LMU, recruiting former and recently recruited ones. It covers basic research investigating the consequences of genetic and environmental factors on psychosis in the translation in preventing psychosis in children of parents with severe mental illness. Secondary prevention aims to avoid further episodes having foci on translation of new mechanisms targeting family communication, patterns of cannabis use or targeting cognitive biases in metacognitive training. Translation in later phases of psychoses refer to translating the knowledge, its evidence and meta-analysis. Novel foci include psychoeducational groups for close relatives of patients with borderline personality disorder and lifestyle behaviors combined with metabolic disturbances in a transdiagnostic psychiatric sample. Recently, metacognitive training gained importance being an important addition to family therapy and cognitive behavioral therapy. Strategies that proved their effectiveness are to be implemented in standard treatment as well as strategies implemented to train professionals in effective crisis and family management.In the nineteenth century, Emil Krapelin  pioneereThis special supplement related to the Eighth Kraepelin Symposium—Translation in Psychiatry and Psychotherapy—A Life-long Necessity  covers tTranslation from mechanism to mental health practices covers basic research in psychological targets in trauma and its translation in mental health practices . TranslaThe vulnerability–stress-coping model (2–3.5) is our conceptual framework guiding psychoeducational and family therapy focusing on the interaction between biological vulnerability, protective personal and environmental factors Garosi et al. and the real world FACE-SZ cohort  investigWright et al.  investigBighelli et al.  investigNovel foci include psychoeducational groups for close relatives of patients with borderline personality (BPD). Pitschel-Walz et al.  evaluateIn summary, the vulnerability-stress-coping model provides valuable targets for treatment stressing psychoeducation, family therapy and cognitive behavioral therapy (CBT) and recently MCT proved their effectiveness in meta-analysis. Psychoeducation, communication, and problem-solving skills are the main tools for relapse prevention. Novel trends refer to pioneering psychoeducational groups in borderline personality disorder, cannabis patterns in first episodes and predictive capability for weight gain during treatment in a transdiagnostic sample.Primary intervention is to focus on psychological targets in trauma in children of parents with PHSMI and there should be visiting and complex community programs, residential treatments and online help. Further research, as well as more training for professionals on effective crisis and family management seems necessary.


Case reports are vital components of scientific literature, providing essential insights into rare or unique medical conditions, diagnostic dilemmas, and therapeutic challenges . There hClinical case reports correspond to articles with the lowest level of evidence on the hierarchy of various research study types . HoweverMedical literature is often dominated by observational studies involving larger patient cohorts, leaving rare and unusual cases underrepresented. Case reports fill this gap by presenting detailed accounts of such unique situations that can be useful for other clinicians . Within The diverse range of respiratory diseases often presents diagnostic challenges due to overlapping clinical features. Case reports detailing unique diagnostic dilemmas and the strategies used to resolve them offer valuable learning opportunities for healthcare professionals . By sharCase reports can provide early evidence of the effectiveness of novel therapies or management strategies for different conditions . In instPneumocystis jiroveceii pneumonia, which exhibited a positive response to endobronchial Watanabe spigot and blood coagulation factor XIII supplementation . In the same way, others atipical respiratory infection are exposed in this Research Topic. Sun et al. described a chronic respiratory condition due to Fusobacterium nucleatum in pleural effusion associated with squamous cell carcinoma. Similarly, Yuan et al. presented a case with Actinomyces graevenitzii, Zhang et al. illustrated an abnormal Streptococcus pneumoniae thoracic image presentation, Peng et al. showed a hypervirulent Klebsiella pneumonia, and Liu and Gao described an infection with Chlamydia psittaci in severe pneumonia cases. All these cases had a positive clinical resolution after identification of the pathogen by molecular sequencing. Unfortunately, molecular diagnostics by next-generation sequencing is not a procedure accessible at the most respiratory centers in the world. In this context, these published cases are important to propose management of rare infection cases in respiratory field.For example, in this Research Topic, we present unusual cases that can provide valuable insights for clinicians facing similar challenges in their practice. One of the cases reported highlights a refractory pneumothorax secondary to human immunodeficiency virus -associated Zuccatosta et al.). The absence of cartilaginous support involvement allowed for successful bronchoscopic treatment, resulting in complete and permanent resolution of the stenosis . Other rare conditions are described in the biliobronchial fistula after cholecystectomy surgery case , a Kartagener síndrome with DNAH9 mutation case , an anomalous systemic arterial supply to the left lower lung lobe , an epithelioid hemangioendothelioma in main bronchus , and tracheal lobular capillary hemangioma . These reports offer important clinical knowledge and potential solutions for managing complex respiratory conditions.Another intriguing cases involved abnormalities in the thoracic anatomy. A post-COVID-19 tracheal stenosis with fibrotic bridges, leading to significant respiratory distress (Finally, this type of evidence serve as powerful teaching tools, especially in medical education . They prDespite representing the lowest level of evidence, clinical case reports continue to be among the most significant sources of knowledge in the biomedical field. They offer valuable insights into unusual disease presentations and the benefits of employing unconventional approaches in treatment . MoreoveRT-C: Writing – original draft, Writing – review & editing. ST: Writing – original draft, Writing – review & editing.


Pseudomonas aeruginosa PAO1 biofilm cell clusters. These P. aeruginosa cell clusters are in vitro models of the chronic P. aeruginosa infections found in adult cystic fibrosis patients, which display resistance to antibiotic treatments, leading to exacerbated morbidity and mortality. This resistance has been partially attributed to periphery sequestration, where antibiotics are unable to penetrate biofilm cell clusters. The underlying physical phenomena driving this periphery sequestration have not been definitively established. This paper introduces mathematical models to account for two proposed physical phenomena driving periphery sequestration: biofilm matrix attachment and volume-exclusion due to variable biofilm porosity. An antibiotic accumulation model which incorporated these phenomena was able to better fit observed periphery sequestration data compared to previous models.A spatiotemporal model for antibiotic accumulation in bacterial biofilm microcolonies which leverages heterogenous porosity and attachment site profiles replicated the periphery sequestration phenomena reported in prior experimental studies on  To solve the time-dependent governing equations for dynamic concentration profiles, the method-of-lines technique was incorporated into the same solver system. Additionally, a variable liquid-interface concentration boundary replaced the constant concentration BC for this dynamic solver due to the observed dynamic BC in the literature data. Relative antibiotic concentrations were inferred from Tseng et al using WebPlotDigitizer (To solve the steady-state form of governing equations used in this paper for equilibrium concentration profiles, a finite-differences solver based on spatial discretization along with the Newton-Raphson technique for the resulting set of non-linear equations was implemented in python in the SPYDER IDE, with code available on Github (igitizer .Supplement 1