Purpose: In the era of precision medicine, target-therapy with monoclonal antibodies (mAb) has enabled new treatment options in patients affected by eosinophilic granulomatosis with polyangiitis (EGPA). Nevertheless, sometimes unsatisfactory results at a nasal level may be observed. The aim of this study is to describe reboot surgery as a potential adjuvant strategy in multi-operated, yet uncontrolled EGPA patients treated with Mepolizumab. Methods: We performed reboot surgery on EGPA patients with refractory CRSwNP. We obtained clinical data, nasal endoscopy, nasal biopsy, and symptom severity scores two months before surgery and 12 months after it. Computed tomography (CT) prior to surgery was also obtained. Results: Two patients were included in the study. Baseline sinonasal disease was severe. Systemic EGPA manifestations were under control, and the patients received previous mepolizumab treatment and previous surgery with no permanent benefits on sinonasal symptoms. Twelve months after surgery, nasal symptoms were markedly improved; endoscopy showed an absence of nasal polyps and there were fewer eosinophils at histology. Conclusions: We presented the first experience of two EGPA patients with refractory CRSwNP who underwent non-mucosa sparing (reboot) sinus surgery; our results support the possible adjuvant role of reboot surgery in this particular subset of patients. Eosinophilic granulomatosis with polyangiitis (EGPA) is an antineutrophil cytoplasmic antibody (ANCA), associated with systemic small-vessel vasculitis characterized by eosinophil-rich necrotizing granulomatous inflammation and hypereosinophilia . EGPA isThe standard systemic treatment for EGPA consists of oral corticosteroids (OCS) and immunosuppressants  . More refull or partial, according to whether a Draf III frontal senotomy is performed. The removal of diseased mucosa, in a particular subset of patients affected by recalcitrant drug-resisting type 2 CRSwNP, has proven to be more effective in obtaining disease control as compared to the standard mucosa-sparing technique, improving both recurrence free survival, quality of life outcomes, and the need for OCS treatment [The purpose of this study is to evaluate if non-mucosa sparing (reboot) ESS can have an adjuvant role in EGPA patients with refractory sinonasal disease. Reboot surgery, as described by Alsharif et al. , is clasreatment ,13. Thisreatment ,12.In the era of precision medicine and personalized treatments, we advocate that it is useful to investigate whether selected patients’ subsets  could benefit from this innovative surgical strategy.The study was approved by our Institutional Review Board (protocol number: ICH/320/21), and it followed the indications of the Declaration of Helsinki and its later amendments. All participants have signed informed consent for the collection and use of their clinical data. Two female patients, 56 and 59 years old, were referred to our Otorhinolaryngology Department. They received a diagnosis of EGPA, respectively, 6 and 3 years prior to referral and had been under treatment with Mepolizumab for 12 months since diagnosis, at dosage of 300 mg every 4 weeks. Both patients’ treatment was discontinued due to symptom control failure and lack of patient compliance. At referral, medical history was collected, the 22-item Sinonasal Outcome Test (SNOT-22) and a Visual Analogue Scale (VAS) for all nasal symptoms were determined. The Nasal Polyp Score (NPS) was assessed through a nasal endoscopy and the Lund-MacKay score (LM) with a maxillo-facial computed tomography (CT) scan. In addition, an ethmoidal mucosa biopsy was performed pre-operatively under local anesthesia . Both pa3/mL; patient #2 = 180 × 103/mL) and previous EGPA manifestations  were absent, demonstrating a stable control of systemic disease; even so, nasal symptoms were still severely affecting both patients , with the early recurrence of symptoms soon after the last procedure . At the time of referral, peripheral eosinophilia was within normal ranges , the query of whether reboot surgery has an adjuvant role in the context of patients with refractory sinonasal manifestations should be raised. To the best of our knowledge, this is the first study concerning the role of reboot surgery in EGPA patients with CRSwNP.Notably, our two cases frequently resorted to the use of OCS for otherwise uncontrollable sinonasal disease manifestations before the extended ESS. Indeed, most EGPA patients use a very high cumulative dose of systemic corticosteroids throughout the disease course, implying a significant burden of steroid-related side effects in this population. As a matter of fact, steroid-sparing strategies are also currently a focus of clinical investigations in patients with ANCA-associated vasculitis ,14,15. IUnfortunately, we were able to include only two patients in the study, so our results should be interpreted in the context of a clinical experience and are not suitable for drawing definitive conclusions. Moreover, patients were referred to our unit only for ENT surgical evaluation and follow-up, which by protocol lasted 1 year. Further investigations with larger patient cohorts, a control group receiving standard sinonasal surgery, and a longer follow-up are needed to define the potentially crucial role of reboot surgery in aiding the long-term control of sinonasal symptoms in locally uncontrolled EGPA patients.In the era of personalized medicine, targeted therapy will become the treatment of choice in systemic immune-mediated chronic conditions. However, in the case of a lack of complete response, clinicians should consider alternative therapeutic strategies. In EGPA patients, nasal involvement can behave independently of systemic disease control and might not respond to standard optimal therapies. We presented the first, albeit preliminary, experience of two EGPA patients treated with Mepolizumab, but still with suboptimal results at a nasal level, who underwent non-mucosa sparing (reboot) sinus surgery; our results support the possible adjuvant role of this approach in a particular subset of patients, with potential benefits in quality of life and ending the need to resort to OCS to treat refractory sinonasal disease manifestations. ENT surgeons need to re-elaborate their thinking about extended ESS (reboot), deviating from standard mucosa-sparing techniques that are likely to be ineffective, but further research is needed to draw definitive conclusions.


The co-evolutionary relationship between plants and microbes has led to complex mechanisms of offense and defense, primarily centering on the innate immune system of host plants countering the virulence determinants employed by pathogens . Both abThe molecular events occurring between plants and both ‘friendly’ and ‘hostile’ microbes trigger a range of highly dynamic plant cellular responses within the plant. These responses play a crucial role in pathogen recognition and the induction of appropriate signaling pathways for effective defense .Unraveling Plant-Microbe Interactions: From Ecology to Mechanisms, Volume II” encompasses various aspects of plant-microbe interactions and explores several intriguing questions. These include: why do certain microbes target specific plants while ignoring others? Is it due to the lack of necessary tools for infecting certain plants, or do some plants possess superior defense mechanisms to counteract such attacks? Is there a lack of attraction between the microbe and the plant? How do plants defend themselves in response to pathogen attacks? What mechanisms do they employ to recognize and counteract pathogens? How do plants interact with beneficial microorganisms? What are the molecular events and signaling pathways involved in establishing symbiotic relationships between plants and helpful microbes? Finally, how do plant pathogens respond to antagonistic microorganisms, and how does this response impact the effectiveness of biocontrol strategies?The Research Topic “Phytophthora  on the expression of resistance (R) genes regulated by the RNA-directed DNA methylation pathway (RdDM). Specifically, the authors studied the role of NO-dependent redox targets involved in the tuning of the R gene expression by complementary miRNA during the potato-avr P. infestans interaction. The researchers proposed that biphasic waves of NO released in response to P. infestans play a crucial role in the successful establishment of resistance to late blight in potato through the RdDM pathway controlling R gene expression.Philosoph et al. explored the response of cucumber plants to co-infection with two distinct pathogens: Pythium spinosum, a necrotrophic pathogen, and Cucumber green mottle mosaic virus (CGMMV), which belongs to a different kingdom and has a different lifestyle. An intriguing finding from their research is the rapid downregulation of host defense gene activity associated with defense against necrotrophic pathogens following the establishment of the virus in plants previously infected with Pythium. The study by Philisoph and colleagues provides valuable insights into the complex interactions and regulatory processes involved when plants face the challenge of co-infection by pathogens from different kingdoms and with distinct lifestyles.In their study, Epichloë, a fungal endophyte, is known to colonize cool-season grasses (Poaceae)  . Zhang eVerticillium wilt, a devastating disease affecting olive trees, poses significant challenges in olive-growing regions worldwide, and its control is notoriously difficult (Cardoni et al. employed a comprehensive approach. Using different olive varieties with varying degrees of susceptibility/tolerance to Verticillium wilt, the authors investigated multiple aspects, including root functional traits, expression of defense-related genes, root lignin content, and membrane permeability. Through their research, the authors successfully identified specific factors that influence the performance of olive trees when confronted with Verticillium invasion.The incidence of ifficult . In an eCandidatus Liberibacter asiaticus (Srivastava et al. present the knowledge, prospective methodology, and open questions remaining in this area of research.Finally, in their review article on the potential role of the microbiome in managing Hualongbin disease in citrus caused by siaticus , SrivastOverall, the articles included in this Research Topic further validate the extensive range of defense mechanisms that plants possess to safeguard themselves against various threats.All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.


Guo Q. et al.), increasing the interest in microbiota modulation as a potential treatment of certain conditions and diseases. However, findings from microbiota-related studies are ambiguous and sometimes difficult to reproduce, while defining what constitutes a “healthy microbiota” still remains a challenge  and gastrointestinal disorders. These studies highlight the emerging interest to develop strategies based on microbiota modulation in disease management and, due to the individual variation on human microbiota, underscore the importance of personalized approaches to promote overall health.Zhao et al. revealed that the success of these interventions is highly dependent on several factors such as dosage, frequency, delivery method and preparation method of donor stool, as well as differences in the microbiota of the selected donors. In particular, direct delivery to the gastrointestinal tract using more invasive routes like gastroscopy or colonoscopy is more likely to lead to significant improvements of IBS symptoms when compared with oral administration. This meta-analysis highlights the need for more standardized intervention processes for the use of fecal transplants when treating specific diseases like IBS.Fecal microbiota transplants have been studied since the 1980s with variying level of success. In the case of the irritable bowel syndrome (IBS), a meta-analysis conducted by Paul et al., the authors delve into the potential role of microbiome therapies in ameliorating biomarkers of inflammation and oxidative stress in patients living with T2D. Compared with individual probiotics, synbiotics, and other prebiotics, multi-strain probiotic combinations and prebiotics like resistant dextrin and inulin seem to be more effective in reducing inflammation and oxidative stress associated with T2D and could contribute to their management. This reduction in oxidative stress and inflammation may also alleviate liver damage .Microbiota modulation represents a promising strategy for improving health outcomes and managing metabolic disorders, particularly T2D and obesity. In a systematic review from Chen et al.). An intervention conducted by Yildrim et al. in children living with obesity, which evaluated the use of multi-strain synbiotic supplementation in combination with a standard diet and increased physical activity, observed significant improvements in anthropometric measurements, including body weight, BMI, and waist circumference. Both studies highlight the synergy between dietary modifications and synbiotics during weight loss, and emphasize the potential role of multi-strain probiotics and synbiotics as part of an effective weight-loss strategy in pediatric obesity.Positive effects of a multi-strain probiotic blend tested on children living with obesity have also been demonstrated, emphasizing how probiotic combinations can be used to reshape the gut microbiota and improve lipid metabolism and reduce body weight . Lactiplantibacillus pentosus P2020 was evaluated as potential preventive strategy for hyperuricemia  using Kunming mice as an animal model. Lactiplantibacillus pentosus P2020 administration was able to reduce serum uric acid levels and mitigate renal inflammation, potentially by regulating inflammatory pathways, enhancing uric acid excretion, and improving intestinal barrier function. In germ-free Fischer 344 rats inoculated with infant fecal microbiota, Rocha Martin et al. studied how Cutibacterium avidum P279 can modulate microbiota composition and activity, reducing H2-producing bacteria with a reduction in symptoms of infant colic. However, the efficacy of these probiotics must still be demonstrated in humans.However, it is not only the combination of different strains that have potential applications for promoting health. The consumption of particular single probiotic strains may confer benefits for the management of specific conditions, as was recognized in guidelines recently published by the World Gastroenterology Organization.Lakshmanan et al. studied the impact of a formulated fruit and vegetable supplement on gut microbiota composition and antioxidant capacity. Supplementation led to changes in microbiota composition and activity, with increased Faecalibacterium abundance and decreased Ruminococcus, along with higher production of short-chain fatty acids (SCFAs). These changes could potentially reduce pro-inflammatory responses and increase antioxidant capacity in healthy adults. In interleukin-10 knockout mice, dietary eggshell membrane supplementation demonstrated significant improvements in survival rates and mitigated gut dysbiosis, suggesting that this supplement might be explored in future studies as a dietary intervention for inflammatory bowel disease in humans . Interestingly, Beaumont et al. proposed that specific amino acids my be used as a novel type of prebiotics due to their selective use by intestinal bacteria and the positive impact on host health, or as synbiotics when combined with specific probiotics. Intermittent fasting (IF) is a dietary approach that has gained popularity in recent years. Mohr et al. evaluated IF as an alternative to daily caloric restriction in adults with overweight and obesity. The study compared one-day and two-day IF protocols combined with protein pacing. While both IF groups exhibited differences in fecal microbiome and plasma metabolome, the two-day IF group displayed distinct metabolic changes in plasma, such as increased levels of specific metabolites, including trimethylamine oxide, levulinic acid, 3-aminobutyric acid, citrate, isocitrate, and glucuronic acid. This research highlights the potential of IF to beneficially modulate microbiota composition and activity and suggests that varying fasting durations may be of interest for specific dietary intervention strategies.Various nutritional and dietary interventions have also been explored to understand their impact on microbiota modulation as an approach to manage different health conditions. Hardinsyah et al.. They hypothesized that salivary microbiome could be used as a diagnostic indicator for T2D. Although the relationship between the salivary microbiome and T2D is complex, with large individual variation in bacterial profiles, metabolic pathways, and oral health status, the authors highlight the potential of salivary microbiome profiling as a rapid, non-invasive test for detecting T2D. As microorganisms can respond quickly to changes in the human body, there is promise in the use of them as biological indicators, for both rapid diagnosis and monitoring the effectiveness of therapeutic interventions.Changes in the microbiome can also be used as novel diagnostic tools of specific diseases, as discussed by Microbiota modulation, as highlighted in our Research Topic, has great potential for improving health. It can positively impact conditions such as obesity, hyperuricemia, constipation, and T2D. The use of fecal microbiota transplants, probiotics, prebiotics, synbiotics, dietary supplements, and dietary interventions demonstrates the versatility of this approach. Future research should focus on refining specific microbial targets, personalized interventions, and addressing the interplay between diet, microbiota, and health. Additionally, exploringthe microbiome as diagnostic tool, and harnessing microbiota modulation in other less explored areas like cardiovascular health and mental wellbeing, are exciting future possibilities. These studies contribute to set the basis for innovative applications and open the door to new frontiers in microbiota-related research.CG-G: Writing—original draft, Writing—review & editing. HE-N: Writing—original draft, Writing—review & editing.


The current study addressed this research gap by analyzing mutual acculturation attitudes in relation to how strongly adolescents self-identify as (1) being Swiss, (2) having a migration background, and (3) the interaction of the two. The sample consisted of 319 adolescents in public secondary schools in three German-speaking cantons in Switzerland . Latent profile analyses resulted in three distinct mutual acculturation profiles. The first is a mutual integration profile , where minority and majority adolescents and schools are expected to integrate. The second is a multiculturalism profile , with slightly lower expectations in all dimensions. The third is a cultural distancing profile , which places particularly low expectations on majority adolescents and schools. Through an analysis of variance and a multiple logistic regression, those in the cultural distancing profile were found to identify significantly stronger as not having a migration background compared to those in the mutual integration profile. Thus, students having separation expectations toward minority students and non-involvement expectations toward schools and majority students are more likely to self-identify as not having a migration background than students having mutual integration expectations.Acculturation is a mutual process, meaning that members of minority as well as majority groups acculturate and thus experience cultural and psychological changes when having intercultural contact. This study assessed mutual acculturation attitudes in the school context through a four-dimensional measurement examining attitudes toward (1) migration background students' heritage culture maintenance and their (2) dominant culture adoption, (3) majority students' intercultural knowledge acquisition, and (4) schools' intercultural contact endorsement. Acculturation attitudes are commonly analyzed through minority and majority perspectives; however, the ways in which researchers categorize group members can differ significantly from how those members self-identify. This matters particularly for adolescents because they explore group identities and belongings. So far, adolescents'  Accordin Berry, , institun Berry,  and thein Berry, . The latn Berry, .mutual acculturation refers to how both minority and majority group members acculturate. Moreover, following an ecological perspective  being Swiss, as (2) having a migration background, and (3) the interaction of the two.Acculturation attitudes are commonly analyzed through minority and majority perspectives and group categorizations are essential to make diverse experiences and attitudes evident , and majority acculturation relates to the acculturation of individuals possessing the Swiss nationality as well as Swiss institutions.To clarify, the terms Connell, . Thus, tConnell, . Thus, Sad cultura, which mean “leading to a culture” , assimilation/melting pot , separation/segregation , and marginalization/exclusion , followed by 6 years of primary school (age 6–12), and 3 years of secondary school (age 12–15) with each canton having different names for the diverse school levels . The specific curriculums used to be defined by each canton independently. In 2014, however, the so-called Lehrplan21 was introduced for German-speaking and bilingual cantons: It defines a shared curriculum that should be implemented until 2021 . Thus, the log odds of self-identifying as not having a migration background were significantly higher in the cultural distancing profile than in the mutual integration profile, confirming the findings of the ANOVA. However, the results indicated no significant interaction between self-identification as being Swiss and as not having a migration background in relation to mutual acculturation profile membership . Adolescents in the mutual integration profile were indecisive concerning the adoption dimension , meaning that they agreed with the adoption of some issues and disagreed with the adoption of others. Because the final adoption score reflects the mid-point of the 4-point Likert answer scale, this pattern is still considered to be an integration pattern. The multiculturalism profile was defined by agreement with the heritage culture maintenance dimensions; however, this profile featured a tendency to agree with only the two majority dimensions and a tendency to disagree with the dominant culture adoption dimension. Multiculturalism refers to a society in which various distinct cultural groups are considered to be relevant and given the agreement concerning migration background students' heritage culture maintenance and the tendency to agree that majority students' intercultural knowledge acquisition and schools' intercultural contact endorsement are important, this pattern was defined as a multiculturalism pattern. Finally, the cultural distancing profile demonstrated a tendency to agree with the heritage culture maintenance dimension and a tendency to disagree with the dominant culture adoption dimension and disagreement with both majority dimensions. The three profiles found in this study resemble the three profiles found in the first year of the longitudinal data collection  and a non-involvement expectation toward majority group members and schools (instead of an integration expectation). Thus, there were exclusionary and distancing tendencies in the cultural distancing profile in that minority group adolescents were not expected to adopt dominant cultural characteristics in Switzerland while Swiss adolescents and Swiss schools were not expected to acquire intercultural knowledge and foster intercultural contact. Adolescents expecting minority group members to separate were more likely to self-identify as belonging to the national majority compared to adolescents expecting minority group members to integrate. This aligns with previous findings in Switzerland concerning students reproducing exclusionary and/or assimilationist practices  being Swiss, (2) having a migration background, and (3) the interaction of the two. Whereas, this study's focus lied on self-identification within national power structures, further research could assess national and ethnic self-identification and their combinations in a more nuanced way. Specifically, diverse ethnic self-identifications , binational identifications , as well as internal migration and therefore cantonal self-identifications  could be studied. Similarly, the mutual acculturation measurement assesses attitudes toward minority and majority groups to focus on social power structures. However, it could be further developed to measure mutual acculturation attitudes toward specific minority groups . This would allow to assess attitudes of specific minority groups toward other minority groups as well as attitudes of the majority group toward different minority groups. Stereotyping and discriminating attitudes can only be discovered through such specified data. Then, as adolescents' self-identifications develop over time, a longitudinal assessment would yield better understanding. Finally, further research is needed to assess self-identification within societal power structures and understand the impact of dominant societal narratives on not only adolescents' self-identification and development thereof but also concerning how self-identification might shape mutual acculturation attitudes or vice versa.mutual acculturation attitudes have so far not been studied in relation to national self-identification measures. This study addressed this research gap by examining adolescents' mutual acculturation attitudes in relation to whether they self-identified as being Swiss, as having a migration background, and the interaction of the two. With latent profile analyses, I identified three mutual acculturation profiles: (1) a mutual integration profile—where migration-background and Swiss adolescents and schools are expected to integrate—and (2) a multiculturalism profile—considering diverse cultural groups as well as intercultural knowledge and contact as important—as well as (3) a cultural distancing profile with separation expectations toward minority adolescents and non-involvement expectations toward majority adolescents and schools. Across the three profiles I found a general acceptance of cultural diversity. Moreover, the three profiles vary most concerning the two majority acculturation dimensions, indicating that the acculturation of majority group members and schools is a distinctive feature of the three patterns. Thus, the patterns clearly show the added value of a mutual acculturation framework, which combines minority, majority, and institutional acculturation. Concerning mutual acculturation attitudes and national self-identification, I found that those in the cultural distancing profile self-identified significantly stronger as not having a migration background than those in the mutual integration profile. However, as this was a cross-sectional study, the direction of this link is unclear and could be assessed by future studies.This study's main aim was to assess whether adolescents' mutual acculturation attitudes varied depending on their national self-identification. Mutual acculturation is a process by which members of minority and majority groups—the latter including national institutions—adjust to and change because of intercultural encounters. Minority and majority perspectives are frequently used to examine acculturation attitudes; however, researchers frequently distinguish between minority and majority group members based on concepts such as place of birth, nationality, migrant generation, or migration background. However, researchers may classify members of a group differently than the group's members self-identify. Adolescents' The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by Ethics Committee of the Faculty of Arts and Social Sciences of the University of Zurich. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.PS participated in the study design and data collection, performed the statistical analysis and data interpretation, and wrote the manuscript.


The establishment of the basic architecture of the brain requires the formation of connections between neuronal axons and dendrites, which results in the generation of functional neural circuits  gene variants associated with Galloway-Mowat syndrome (GAMOS) in Chinese children. GAMOS is a genetically heterogeneous, autosomal recessive disorder characterized by brain developmental impairment and presenting with microcephaly, developmental delay, and intellectual disability. Pathology in GAMOS type 4 (GAMOS4) results from defective TP53RK function. Interestingly, nephrotic syndromes are absent from patients in this study, in contrast to observations in previously reported GAMOS4 cases. This work improves mechanistic and diagnostic insights into the disease, highlights the potential impact of single gene mutations on neurodevelopment, and suggests the contribution of alternate factors to disease manifestation, reminiscent of the majority of neurodevelopment disorders.Here, through whole-exosome sequencing, Lee et al. describe how the presence of known mutations in the chromatin remodeler CHD8 gene may contribute toward brain alterations underlying autism spectrum disorder (ASD) presentation. Interestingly, this paper highlights the sex- and age-dependency of CHD8 mutations on synaptic and transcriptomic changes in mice. Specifically, the authors report that CHD8 mutations result in reductions in excitatory synaptic transmission in juvenile male mice, that correlated with ASD-like behaviors. However, mutations lead to increased excitatory transmission in female mice with comparatively normal behavior, suggesting that reductions in the neuronal excitatory-inhibitory balance may account for ASD development in a sex-dependent manner.Wei et al. describe how Parkinson's disease (PD) pathology may arise from mutations in the leucine-rich repeat kinase 2 (LRRK2) coding gene—one of the most common gene modifications in human PD patients . They provide first-hand evidence of the involvement of altered inhibitory synaptic vesicle exocytosis, reduced bouton density and impairment of inhibitory neurotransmission at the presynaptic domains of striatal neurons in neurological pathology observed in the zQ175 rodent HD model. The study emphasizes the importance of cellular function maintenance for optimal neurological health.Alterations to vesicle transport and synaptic trafficking lead to synaptic loss and plasticity changes linked to prodromal neurodegeneration  methylation, the most abundant internal RNA modification in eukaryotic cells, is strongly linked to learning and memory processes in the brain. Although the precise role of m6A RNA methylation is unclear, changes in m6A levels in the nervous system are associated with synaptic alteration in aging and neurodegenerative diseases. This review presents a link between m6A methylation and the function of the neurovascular unit, and its likely neuroprotective effects which may contribute to neurofunction recovery in neurodegenerative disease.Epigenetic modifications describe regulatory processes that control gene expression. Therefore, gene alterations depend not only on initial genetic variability in the DNA sequence but also on the nature of posttranscriptional RNA modifications. Shin and Lee investigated the effect of environmental-dependent, early-life stress associated with maternal separation on cognitive development in mouse pups. They observed that adolescent mice display varying alterations in cognition, dependent on their environmental context during exposure to neonatal maternal separation. This study therefore presents comprehensive early-life stress models that may provide the impetus for further understanding environmental contributions to neuropsychiatric conditions such as anxiety and depression.Besides genetic alterations, the impact of environmental factors on neurological function cannot be understated. Zhao et al. point to the role of ventral tegmental area projections to the basolateral amygdala in encoding anxiety, but not depressive-like behaviors, presenting a novel neural circuitry target for anxiety-specific treatment. This study emphasizes the importance of studying anxiety and depression as independent disorders involving unique brain circuitry. A deeper understanding of these distinct changes can promote the development of more effective, highly-targeted treatments with improved therapeutic outcomes and fewer side effects.In addition to their common standalone occurrence, psychiatric conditions often present as comorbidities of a range of neurological disorders. However, current treatment options are known to result in further neurological disturbance and new psychiatric side effects (Haddad and Dursun, The studies presented in this Research Topic highlight novel insights into the involvement of genetic and environmental factors in neurological function and pathology. We hope that these findings from experts within the field will contribute to enhancing our understanding and thus promoting further advancements in the prevention, diagnosis, and treatment of brain diseases.GC: Writing—original draft. XY: Writing—review and editing. SJ: Writing—review and editing, Writing—original draft.


Doulas have been instrumental in providing breastfeeding support to nursing mothers before and during the COVID-19 pandemic, as they can significantly impact a mother's ability to initiate and maintain breastfeeding. However, the COVID-19 pandemic, subsequent lockdowns, and social isolation created challenges for nursing mothers to access doulas' services, usually provided in person. In this study, we examined the role of doulas in providing breastfeeding support during the COVID-19 pandemic, exploring adaptation to COVID-19 guidelines and the challenges doulas face in providing breastfeeding support during the pandemic.A systematic review was conducted following the PRISMA guidelines. Thirteen scientific databases and twenty peer-reviewed journals were searched for journal articles published in English between January 2020 and March 2022 using key search terms . Studies evaluating the role of doulas in providing breastfeeding support during COVID-19, and the impact of COVID-19 Guidelines on doula services, were included. Two reviewers independently performed the risk of bias assessment and data extraction. Summative content analysis was used to analyze the data.The majority of studies were conducted in developed nations. This systematic review includes eight articles, four qualitative, one survey, two mixed-methods studies, and one prospective research study. Seven of the eight studies were conducted in the United States, and the eighth was conducted in multiple countries. These studies have three main themes: (1) virtual breastfeeding support provided by doulas during the pandemic; (2) remote social support provided by doulas to breastfeeding mothers during the pandemic; and (3) barriers to doula service delivery due to COVID-19 restrictions, primarily the exclusion of doulas as essential workers. The eight studies showed that doulas found innovative ways to serve the needs of birthing and nursing mothers during the difficulties brought on by the pandemic.Doulas provided breastfeeding support during the COVID-19 pandemic by utilizing innovative service delivery methods while navigating changes in COVID-19 guidance. However, system-level integration of doulas' work and the acknowledgment of doulas as essential healthcare providers are needed to enhance doula service delivery capacity, especially during a pandemic, to help improve maternal health outcomes. The restrictions on non-essential gatherings, social distancing, and redirection of public health infrastructure were just a few of the diverse, wide-ranging strategies to mitigate and control the spread of COVID-19 around the globe –5.Doulas are birth workers who care for birthing people and their newborns—usually trained or certified community members who can serve and provide culturally appropriate maternal and reproductive health care , 6, 7. TThe World Health Organization (WHO) recommends that newborns commence breastfeeding within an hour of birth, breastfeeding exclusively for the first half of their first year, and continue breastfeeding with the addition of complementary meals for at least two years . This reBreastfeeding support has inevitably changed due to COVID-19, with rates of exclusive breastfeeding among nursing mothers steadily declining , 19. DelThis systematic review examines the role of doulas in providing breastfeeding support during the COVID-19 pandemic and how community-based doula services adapted to changes in COVID-19 guidance to provide breastfeeding support during the pandemic.Cochrane Handbook for Systematic Reviews of Interventions [A systematic review was conducted in accordance with the PRISMA guidelines . Thirteeventions . There wGoogle Scholar and the Web of Science were utilized to collect references and citation searches. The authors established current awareness alerts in databases such as MEDLINE, Embase, Web of Science, and Google Scholar to locate recent work. The authors conducted an iterative search to increase sensitivity, address indexing difficulties, and leveraged the Web of Science to find essential and influential electronic health journals. Manual searches were conducted by checking the online table of contents and using the journals' search engines Table .A."doula" or "birth assistant" or "delivery companion" or "breastfeeding companion" or "childbirth companion" or "birth companion" or "birth partner" or "breastfeeding assistant" or "supportive companion" or "pregnant outreach" or "nursing companion" or "breastfeeding support" or "breastfeeding coach" or "all feeds."B."Breastfeed" or "human milk" or "infant nutrition" or "lactation" or "human lactation" or "breast milk" or "lactation" or "all feeds."C.“Coronavirus” or “SARS-CoV-2” or “COVID-19” or “corona virus or “pandemic” or “coronavirus pandemic” or “SARS-CoV-12 pandemic or "all feeds."The search terms used included the following.Authors obtained forty-three publications from 13 bibliographic databases, search engines, and manual searches. Following the database search, citations were added to Mendeley; duplicates were identified, eliminated, and then imported into Rayyan, where the remaining duplicates were deleted . The Critical Appraisal Skills Program (CASP) approach for systematic reviews was utilized to evaluate the quality of the publications . The titPapers that examined the role of community doulas in providing breastfeeding support to nursing mothers during the pandemicPapers that explored the role of community-based doula programs and delivery methods during the COVID-19 pandemicPapers that discussed how community-based doula services adapt to changes in COVID-19 guidance to provide breastfeeding support during the pandemic.Papers that explored how community-based doula care has impacted maternal health and service delivery during the COVID-19 pandemic.Inclusion and exclusion criteria were developed using the study research questions. Studies that used qualitative methods  and quantitative studies, mixed-method studies, and randomized-controlled trials were included. Also, full-text articles in English published in peer-reviewed journals between January 2020 and March 2022 were included. Other inclusion criteria were:ReviewsSecondary analyses Articles excluded were:In addition, papers in languages other than English, articles without full-text, papers that scored eight or less using the CASP tool, those not directly related to the topic or population of interest, and research conducted before January 2020 were excluded.The eight articles in this systematic review include four qualitative, one survey, two mixed-methods, and one prospective research study. Seven of the eight were conducted in the United States, and the eighth was conducted in multiple countries. Participants in these studies were birth workers, including doulas. The search identified forty-three publications: 15 in MEDLINE, 8 in EMBASE, 6 in CINAHL, 4 in PsycINFO, and 10 in the other databases  fear of exposure, (ii) limited access to their intended support systems, including doulas, and (iii) uncertainty about hospital restrictions and COVID guidelines on labor and delivery , 26, 31.Two studies included in this review examined the impact of hospital and clinic restrictions, including restrictions on the attendance of birthing support staff, including doulas. Oparah collected narratives of Black and Latinx birth workers , 29. In In examining Black and LatinX community-based doula work transitions in the United States during the Pandemic, Rivera (2021) found that doulas had to adapt to new ways of delivering services to keep themselves, their clients, and the community safe. Doulas reached their community and birthing clients through free virtual childbirth courses, including breastfeeding support .In an inThis review presented evidence that doulas played crucial roles in providing breastfeeding and other maternal health support to birthing people throughout the pandemic while utilizing innovative ways to adapt to COVID-19 guidelines and health system policies. Common themes in the literature were that the COVID-19 guidelines and health system policies relegating doulas to non-essential personnel substantially impacted their capacity to adequately assist their clients during the pandemic, especially in the areas of breastfeeding and emotional support , 25, 27.Doula activities during the COVID-19 pandemic have significant policy implications that can affect the workforce pathway and indicate ways the workforce could be improved or further mobilized. Given the proper recognition and support, doulas and birth workers can provide more appropriate services to pregnant and nursing mothers.Increasing access to high-quality care for all people giving birth, especially in underserved communities, through integrating doulas into the health systemRecognizing birth doulas as essential care team members in hospitals and other healthcare facilities and insurance companies covering doulas' servicesUsing the same guidelines for doulas and birthing workers as those used for other medical professionals during the pandemicSupporting laws to enhance the sustainability of care models that utilize community-based doulas.Areas for consideration include:Most articles in this systematic review focus on US doula activities during the COVID-19 pandemic. These recommendations reflect policies in the United States but may be adapted for use by doulas and policymakers worldwide.The studies included in this systematic review have demonstrated the value of doula care during the pandemic regardless of the COVID-19 guideline restrictions. Doula care can help close inequity gaps by improving access to patient-centered, culturally appropriate, customized treatment and advocacy in medical environments where such investments may not be present. Integration of doulas into collaborative maternity approaches strengthens the care team's response to birthing people.Future research should examine the work of doulas during the pandemic and studies that provide baseline data for advocacy policy implementation that will fully integrate doulas as essential to the healthcare workforce. Research should also focus on the perspectives of birthing people at risk for adverse maternal health outcomes, informing how doula care can help mitigate health disparities. It will also be vital to examine how doula services can be fully integrated into the health system and how that may correlate with health outcomes for birthing people and families, especially during a pandemic. Although there is preliminary evidence of the modifications made to the lactation field in response to COVID-19, more research into these modifications and their long-term effects is necessary.A significant limitation of this review is that most of the articles were studies conducted in the United States. It does not offer a comprehensive view of doulas in other countries and their approaches to providing care during a pandemic. Additionally, this review relied on the critical appraisal of individual studies, and the interpretation of results in each paper examined. Despite these limitations, this study contributes to the larger body of literature on doula care approaches during the COVID-19 pandemic by highlighting their role in supporting the maternal and child health continuum in emergency and non-emergency situations. Additionally, this review supports the calls for system-level integration of doulas' work and the need to recognize doulas as crucial healthcare professionals who can contribute to improving maternal health outcomes.Doulas provide their clients with vital maternal health services despite the hurdles presented by the COVID-19 pandemic. They use innovative service delivery methods to offer breastfeeding support while navigating changes in COVID-19 guidance. By deeming them non-essential and disregarding their role in advancing maternal health services during the pandemic, the healthcare system may have missed an opportunity to integrate a dependable workforce into the maternal health continuum that can assist in improving health outcomes for mothers and children. System-level integration of doulas' work and the acknowledgment of doulas as essential health care providers are needed to enhance doula service delivery capacity, especially during a pandemic, to sustain positive maternal health outcomes.


Insects have been consumed as food in diverse cultures worldwide, gaining recognition as a sustainable and nutritious food source. This systematic review aims to update information on the impact of insect consumption on human health based on human randomized controlled trials (RCTs) and allergenicity assessment studies. Following PRISMA guidelines, studies published in the last 10 years were analyzed. From one-thousand and sixty-three retrieved references, nine RCTs and five allergenicity studies were analyzed. Post-prandial amino acid levels increased after insect protein consumption. In comparison with other protein sources, insect protein showed no significant differences in the area under the curve (AUC) values for essential amino acids but tended to have lower peaks and peak later. In terms of muscle protein synthesis, there were no significant differences between insect protein and other protein sources. Glucose levels did not differ; however, insulin levels were lower after the consumption of insect-based products. The effects on inflammatory markers and microbiota composition were inconclusive and the studies did not show significant effects on appetite regulation. Allergenicity assessments revealed a sensitisation and cross-reactivity between insect allergens and known allergens. A partial reduction of cross-allergenicity was observed via thermal processing. Insect protein is an adequate protein source with promising health benefits; however, further research is needed to fully understand its potential and optimise its inclusion into the human diet. Edible insects are considered a valuable source of highly nutritious food . Eating Acheta domesticus and the mealworm Tenebrio molitor, as these are the species with greater potential to be used as human food  ,62. AddiCytokines belong to a broad family of proteins associated with inflammatory activity and an imbalance in the cytokine network leads to enhanced inflammation; therefore, cytokines are considered valuable as predictive biomarkers of disease activity. Among cytokines, tumor necrosis factor-alpha (TNF-α) is a principal cytokine, chiefly produced by macrophages, which acts as a potent inducer of other proinflammatory cytokines and chemokines, further enhancing the inflammatory response . In agreBifidobacterium following the consumption of an insect meal with cricket powder [Lactobacillus spp. is known to play a crucial role in maintaining gut health and Bifidobacterium is associated with various health benefits, including improved digestion and immune function [Lactobacillus spp., the increased abundance of Bifidobacterium observed in this study may be indicative of a beneficial shift in the gut microbiota. The authors suggested that the decrease in Lactobacillus could be due to the antimicrobial activity of chitin and chitosan present in cricket powder [Tenebrio Molitor showed an increase in both Bifidobacterium and Lactobacillus [The study conducted by Stull et al. (2018) reported some interesting findings regarding the effects of insect consumption on microbiota probiotics. While they observed a decrease in the levels of Lactobacillus spp., they found increased levels of t powder . Lactobafunction ,66. Despt powder . On the bacillus . These cSCFAs are metabolic by-products of gut bacteria fermentation and are known to have anti-inflammatory and immunomodulatory properties . They alA food allergy (FA) is an adverse reaction to a specific food antigen, normally harmless to the healthy population, which is mediated by immunological mechanisms and arises in individuals susceptible to that specific allergen . Immune The recent introduction of edible insects in Western countries as a novel food has raised preoccupations about their safety in terms of FAs. There were several reports of anaphylaxis following an ingestion of insects by subjects without previous allergic reactions toward insects ,74. TherAllergic reactions to edible insects can be associated with primary sensitization, either through environmental or occupational exposures . Indeed,Regarding food allergen cross-reactivity, crustaceans, such as shrimp, crab, crawfish, and lobster, are a frequent cause of adverse food reactions in allergic individuals . MoreoveGryllus bimaculatus in shrimp-allergic subjects [Gryllodes sigillatus in subjects allergic to shrimp, HDMs or mealworms [Imbrasia belina) and mold mite (Tyrophagus putrescentiae) extracts was observed [Tropomyosin belongs to a family of highly conserved proteins with multiple isoforms and is found in both muscle and non-muscle cells of all species of vertebrates and invertebrates. Allergenic tropomyosins are found in invertebrates, such as crustaceans, arachnids, insects, and mollusks; whereas, vertebrate tropomyosins are nonallergenic . In accosubjects , the measubjects ,37, and observed . The autobserved . Additioobserved .Tenebrio molitor), the field cricket (Gryllus bimaculatus), and the house cricket (Achaeta domesticus), in shrimps, such as the black tiger prawn (Penaeus monodon), the king prawn (Penaeus latisulcatus), and the giant freshwater prawn (M. rosenbergii), and in crabs, such as the blue swimming crab (Portunus pelagicus) [Gryllus bimaculatus), arginine kinase was previously identified as the major allergen responsible for the binding of cricket allergens with IgE in patients with shrimp allergies [Alphitobius diaperinus), mealworm larvae (Tenebrio molitor), cricket (Gryllodes sigillatus), grasshopper (Locusta migratoria) and silkworm larvae (Bombyx mori) proteins extracts [Arginine kinase, the other major invertebrate-pan-allergen, is a protein with a highly conserved amino acid sequence among various invertebrate species. Arginine kinase is widely distributed in various insects, such as the yellow mealworm (lagicus) . Many allagicus) . In agrelagicus) . Howeverlagicus) ,37, nor lagicus)  , hexamerin, α-amilase, and many others, such as apolipophorin III, the chemosensensoryprotein, the cockroach allergen-like protein, the receptor for activated protein kinase, the heat shock protein (HSP) 70, or the odorant-binding protein. These proteins have arisen as being very specific to edible insects and, despite this, are much less present in arthropods, mollusks, or nematodes; they share well-conserved amino acid sequences and highly similar quaternary structures ,82. The LCPs are a well-conserved group of proteins that play a key role in the deposition of the newly synthesized chitin chains forming the chitinous shell during the ecdysone-driven molt periods of insect larvae; they closely resemble some other pupal cuticle proteins. LCPs are abundantly represented in the yellow mealworm, most particularly as proteins A1A and A2B ,83. AccoTenebrio-molitor-induced food anaphylaxis [Gryllus bimaculatus as a minor allergen in prawn-allergic patient’ sera and hexamerin-like protein 2 (HLP2) mentioned as a new allergen found in crickets [Hexamerin and α-amilase are other proteins for which sensitization was detected in the patient with phylaxis   and the tropical oyster (Crassostrea belcheri) have been similarly pointed out [Another method was presented via the study of Verhoeckx et al. (2014)  involviny stable . In othented out ,80. Addinted out ,80.For now, according to current European food legislation on novel foods (EU Reg. 2015/2283), insects intended as an alternative source of food proteins for human consumption are considered novel foods. Since food allergens are mostly proteins, greater efforts in the analysis and identification of the potential allergenicity of these novel proteins should be a fundamental activity to ensure a high level of food safety for European consumers. Additionally, including allergenicity assessments as part of the risk assessment of novel food is crucial; they should be carried to the existing allergic population identified by the immunoglobulin E (IgE) cross-reactivity .The results of the studies reviewed contribute to our understanding of the nutritional and health implications of consuming insect protein. Insect protein ingestion leads to a higher area under the curve (AUC) for EAA and leucine compared to beef protein; it is similar to milk and soy protein. This suggests that insect protein can be a suitable alternative used to promote muscle protein synthesis. The presence of chitin in insect-based products may result in a slower digestion rate and a delayed release of the amino acids. Furthermore, the absorption of certain micronutrients, such as iron, may be dependent on the chitin content of the insect species. Regarding metabolic and inflammatory markers, glucose levels did not differ but insulin levels were significantly lower after consuming insect-based products compared to other protein sources. Inflammation markers showed mixed results, with lower levels of tumor necrosis factor observed after cricket consumption. While the reviewed studies provide promising insights into the potential metabolic and anti-inflammatory benefits of consuming edible insects, further research is needed. No significant differences were observed in terms of the desire to eat and the prospective food consumption between insect protein and other protein sources. The impact of insect protein on appetite regulation may be influenced by the specific amino acid composition; more data on the amino acid content of different insect species are needed to fully assess their value in comparison to other protein sources. On the other hand, a significant concern regarding the consumption of edible insects is cross-reactivity, which was observed between insect allergens and known allergens, such as shrimp and house dust mites. Tropomyosin and arginine kinase were two major pan-allergens found in invertebrates; they are associated with allergic reactions to edible insects, along with other minor insects allergens, such as larval cuticle proteins, hexamerin, α-amylase, and several other proteins. Food processing techniques can partially reduce cross-allergenicity in edible insects but the impact may vary. Further studies are certainly needed to explore these allergens and develop effective processing methods to reduce allergies. The strength of this systematic review was its contribution to our understanding of the effects of insect consumption on diverse aspects of human health based on human interventions, such as nutrient absorption, muscle protein synthesis, satiety, microbiota, metabolic, and inflammatory biomarkers. However, limitations existed, such as the reduced number of studies, the lack of participants in some cases, and the sparseness of the available results; due to frequently involving different insect species, creating comparisons was a hard task. More insect species should be investigated, along with a broader range of biomarkers and longer intervention periods, to gain a better understanding of the comprehensive effects of insect consumption on human health.


BMC Oral Health entitled ‘Patient-reported outcomes in dentistry’.Patient reported outcomes have become important, with instruments (patient reported outcomes measures - PROMs) being used to assess treatment success and patient satisfaction. In this editorial, the dental PROM context is presented, and submissions are invited for a special collection from  Historically, clinical dental research primarily relied on clinical inputs from dental professionals. Outcome assessment of dental treatments and oral care emerged on how long they last, whether failure or complications occur, healing rate, survival time assessment, long-term success, identification of risk and protective factors, effects of new materials and techniques, and evaluation of clinical parameters. These outcomes represent the clinician-observed impact of the oral condition or the dental intervention and are more or less objectively measurable . They arHowever, there were concerns that clinical outcomes do not adequately reflect the patients’ experience. Consequently, patient opinion and satisfaction are increasingly becoming important in healthcare research . A patieIn the dental field, PROMs have become essential in evaluating dental treatments’ success. One of the first socio-dental indicators on people`s well-being was the Social Impacts of Dental Disease (SIDD) scale . The SIDThe most widely used PROMs are questionnaires having multiple questions in order to capture specific or general oral conditions or diseases for use with younger and older populations . HoweverPROMs are relevant to all dental specialties, as they provide valuable information on how treatments affect patients’ physical, psychological, and social well-being. Measuring PROs allows for a patient-centered approach to dental care, where treatment success is defined by the patient’s perspective. Current research highlights the importance of using validated instruments and questionnaires , 7.PROMs can provide critical information to clinicians, researchers and policymakers, indicating how well a particular treatment works and how it can be improved considering the patient’s or caregiver’s point of view. Besides, professional training for dental students in most dental schools focus on clinical outcomes. But outcome assessment should be patient-centered and patient-oriented as required by personalized medicine to improve health outcomes for individual patients. More evidence of PROs in dentistry are needed for dental educators before integrating PROs into dental education.BMC Oral Health Collection on Patient-reported outcomes in dentistry. This special issue considers the patient as the center of attention for dental treatment success; it also focuses on patients’ perspectives and measures about dental care and the effect of treatments on their oral health and quality of life.It is essential for dental practitioners, researchers and educators to consider PROs in treatment planning, professional training and decision-making to provide more patient-centered care. This perspective introduces the


This review describes the role of modern preprosthetic surgery. The atrophic edentulous jaw can cause severe functional impairment for patients, leading to inadequate denture retention, reduced quality of life, and significant health problems. The aim of preprosthetic surgery is to restore function and form due to tooth loss arising from congenital deformity, trauma, or ablative surgery. Alveolar bone loss is due to disuse atrophy following tooth loss. The advent of dental implants and their ability to preserve bone heralded the modern version of preprosthetic surgery. Their ability to mimic natural teeth has overcome the age-old problem of edentulism and consequent jaw atrophy. Controversies with preprosthetic surgery are discussed: soft tissue versus hard tissue augmentation in the aesthetic zone, bone regeneration versus prosthetic tissue replacement in the anterior maxilla, sinus floor augmentation versus short implants in the posterior maxilla—interpositional bone grafting versus onlay grafts for vertical bone augmentation. Best results for rehabilitation are achieved by the team approach of surgeons, maxillofacial prosthodontists/general dentists, and importantly, informing patients about the available preprosthetic surgical options. This review article discusses the role of contemporary preprosthetic surgery in managing the consequences of tooth loss, which culminates in the loss of oral function and facial form, and as a result, quality of life and self-esteem are affected. The lack of denture stability causes difficulty when eating in public. Furthermore, these problems are compounded by facial changes, such as a decrease in lower facial height, drooping chin, inverted lips, peri-oral wrinkling, and drooling. The aim of preprosthetic surgery is to improve denture stability and mastication whilst reducing jaw resorption, mucosal irritation fibromata, and possible dysplasia.www.iaofr.org (accessed on 21 November 2023)”) was founded by John Cawood, Franz Härle, Eric Hjorting-Hansen, Hans de Koomen, Soren Hillerup, Hermann Sailer, Paul Stoelinga, Bill Terry, et al. [The term preprosthetic surgery was coined in the 1960s by Professor Hugo Obwegeser. Subsequently, in the 1980s, the International Research Group for Preprosthetic Surgery  to create enough bone volume. Guided bone regeneration is a well-documented technique and is effective in reducing bone defects that remain after implant placement. The aim of GBR is the establishment of a facial bone wall of sufficient thickness and height to support the soft tissues. Long-term GBR studies, in combination with implant placement, have demonstrated that thick and stable buccal bone walls can be achieved after lateral bone augmentation ,10. HoweEven if there is no bone defect and no need for a bone graft, there may be a need for soft tissue grafting to improve the thickness and contour of the facial mucosa. Grafting of the peri-implant soft tissues can be performed before, simultaneously with implant placement, during osseointegration of the implant, or after prosthetic reconstruction . InadequSoft tissue augmentation has also been proposed to re-establish buccal convexity. This approach can be considered when there is sufficient bone for complete embedment of the implant shoulder as well as when minor buccal bone defects causing soft tissue concavities are present ,14,15. TThe materials used for soft tissue grafting can be classified into three categories: (1) subepithelial connective tissue grafts harvested from the patients’ palates or tuberosities, (2) allografts, and (3) xenografts. Soft tissue substitutes (a volume-stable collagen matrix) resulted in similar stable peri-implant tissues, favorable aesthetics, and clinically negligible contour changes at 5 years post-loading than after using a subepithelial connective tissue graft . HoweverIn summary, bone augmentation is needed to reconstruct a deficient ridge to a form that will ensure that an aesthetic implant-supported restoration with a good aesthetic outcome can be fabricated. Soft tissue augmentation is needed to improve the functional and aesthetic outcomes if there is any compromise in soft tissue thickness or quantity. A major limitation of most studies is the lack of long-term results.This section focuses on dentoalveolar reconstruction in the anterior maxilla. Tissue defects in the aesthetic area can be compensated by prosthetic means like artificial gingiva. However, knowledge of surgical procedures, bone remodeling, and osseointegration helps us to find a regenerative solution. When analyzing long-term prognosis and aesthetical results, the use of autogenous bone grafting and alveolar ridge reconstruction is the first choice, provided that the patient is fit for surgery. The aim is that the alveolar bone is adequate in height and width as well as providing support for a natural gingiva covering.Replacement of the dentition in the anterior maxilla is demanding aesthetically, biologically, and biomechanically due to limited alveolar bone volume ,21. TrauThe buccal bone thickness in the anterior maxilla seldom exceeds one millimeter , and couIf the preoperative clinical and radiographic examination indicates insufficient alveolar bone volume, usually, two treatment options can be offered: prosthetic replacement with artificial gingiva (pink porcelain) or with a removable denture. In contrast, pre-implant bone reconstruction provides support for endosteal implants and support for the upper lip and a natural gingival appearance ,30,31,32In severe vertical discrepancies, distraction osteogenesis can be used for reconstruction in the anterior maxilla, but the result compared to onlay bone grafting in terms of bone gain and bone resorption is questionable . Zhao etMarginal soft tissue is also important in the reconstruction of the anterior maxilla. Bienz et al.  concludeImplant placement can also be challenging in the anterior maxilla because of limited interdental space and bone volume, especially in single tooth situations. D’haese et al.  and LaedProsthetic rehabilitation of the moderately atrophic posterior maxilla with an implant-supported restoration is traditionally solved by grafting of the sinus floor for accommodation of standard-length dental implants. This section presents the current knowledge, which indicates that situations of maxillary sinus floor augmentation can be avoided by the use of short implants.Maxillary sinus floor augmentation applying the lateral window technique and placement of a grafting material underneath the elevated Schneiderian membrane is frequently used to increase the alveolar ridge height of the atrophic posterior maxilla A,B. HighProsthetic rehabilitation in the atrophic posterior maxilla with a short implant has been proposed to preclude alveolar ridge augmentation . The defA comprehensive review of the literature identified three randomized controlled trials assessing implant treatment outcomes following single-crown restorations supported by short implants (6 mm) compared with standard length implants (≥11 mm) in conjunction with sinus floor augmentation ,73,74,75In the past, it has often been questioned whether a substantial vertical ridge augmentation with long-term stability is possible because a continuing jaw atrophy, especially in the absence of dental implants, was observed . This seTo be functional, a non-vascularized bone graft must first become integrated and then remodeled by the process of neoangiogenesis within the bone graft. The new blood vessels grow into the graft from the base of the bone defect. Traditionally, onlay bone grafts were mainly used prior to implant placement. According to the quarter classification of bone deficits in the site of a dental implant (Terheyden ), the reNeoangiogenesis inside autogenous block grafts is enhanced by “creeping substitution” which involves “bone-cutting cones” similar to the remodeling of compact bone . It has With onlay grafts, the need for primary coverage causes soft tissue tension when mobilizing the flap, which can result in wound dehiscence with partial or complete loss of the bone graft, which has been reported as high as 33–40%  On the oCoverage of an onlay bone block or vertical guided bone regeneration (GBR) site requires the buccal tissue to be moved crestally, advanced over the graft in a palatal or lingual direction, and finally further stretched down apically to engage the pristine lingual/palatal mucosal margin. This triple flap mobilization usually ends with a palatal or lingual shift of the mucogingival border . The fixBone graft resorption is usually a surface resorption at denuded bone surfaces. During interpositional grafting, the lingual/palatal soft tissues stay attached to the transported bone segment . Only thHowever, the limitations of interpositional grafting should be mentioned. When scar tissue or the rigid palatal mucoperiosteum allows only limited movements of the bone transport segment, distraction osteogenesis may be a better option . The thiThe principles of sandwich grafting of the atrophic mandible have been described in the era of classical preprosthetic surgery . The edeIn the mandible after sandwich osteoplasty, the reported height gain was 8.4 mm in the edentulous atrophic jaw and 4.8 mm in the partially dentate atrophic jaw posteriorly . ImplantModern preprosthetic surgery aims to provide functional and facial aesthetic rehabilitation for patients with complex situations. Preprosthetic surgery should assist general dentists and maxillofacial prosthodontists in a team approach in providing a not-always optimal but always adapted and responsible treatment concept.According to According to According to According to Considering these results, it seems the age-old problem of resorption of the edentulous alveolar bone that plagued our forefathers  has been


Integral membrane proteins are involved in a plethora of biological processes including cellular signalling, molecular transport, and catalysis. Many of these functions are mediated by non-covalent interactions with other proteins, substrates, metabolites, and surrounding lipids. Uncovering such interactions and deciphering their effect on protein activity is essential for understanding the regulatory mechanisms underlying integral membrane protein function. However, the detection of such dynamic complexes has proven to be challenging using traditional approaches in structural biology. Native mass spectrometry has emerged as a powerful technique for the structural characterisation of membrane proteins and their complexes, enabling the detection and identification of protein-binding partners. In this review, we discuss recent native mass spectrometry-based studies that have characterised non-covalent interactions of membrane proteins in the presence of detergents or membrane mimetics. We additionally highlight recent progress towards the study of membrane proteins within native membranes and provide our perspective on how these could be combined with recent developments in instrumentation to investigate increasingly complex biomolecular systems. Integral membrane proteins comprise approximately one-third of the human proteome  and undeUnderstanding how endogenous binding partners and drugs impact the structures and function of membrane proteins is a key step towards elucidating protein structure–function relationships. Advances in experimental and computational techniques have enabled access to hitherto elusive knowledge of membrane proteins’ working mechanisms and their interactions with other biomolecules. These methodological advancements range from developments in membrane protein crystallisation  and soluBy integrating native MS alongside other structural techniques, deep insights into the relationship between protein sequence, structure, dynamics, and function can be derived. The ease of coupling native MS with ion-mobility and hydrogen-deuterium exchange MS enables access to information regarding protein folding, conformation, and dynamics . SimilarThere has been a multitude of excellent, in-depth reviews focused on the study of membrane protein structure by native MS ,31–33. Hn-dodecyl β-D-maltoside) and LMNG  are often considered the preferred detergents for protein extraction and purification from cellular membranes as they create a stable environment for proteins [A fundamental challenge associated with handling membrane proteins outside of their cellular context is to maintain their native fold in aqueous buffers. This is often achieved using detergents, which mimic the phospholipid bilayer ,35. Deteproteins . Howeverproteins ,40. Therproteins ,42. TablExcitingly, new detergents with modified headgroups, linkers, and chain configurations continue to emerge. A notable example in this regard is the development of a ‘tailored’ OGD-based detergent that combines the membrane solubilisation and protein extraction efficacy of DDM with the ease of protein release from C8E4 micelles . SynthesDetergent-purified proteins can also be reconstituted into other membrane mimetics, such as bicelles, amphiphilic polymers, liposomes and nanodiscs, for native MS analyses ,46. HoweAlthough the use of native MS in probing the interactions of membrane proteins has been well described in recent reviews ,33, hereWhile native MS (not coupled with doing multiple rounds of MS/MS), does not provide localisation information on covalent modifications to proteins, it can still play a role in the characterisation of individual proteoforms. Such measurements can enable the effects of PTMs on protein interactions to be directly identified. For example, Harvey et al.  employedn), known as native top-down MS, can enable the identification and characterisation of specific proteoforms and post-translational modifications. In an elegant study, Ro et al. [On the other hand, coupling native MS with tandem MS (MSo et al.  recentlyA more common application of native MS is in the investigation of non-covalent biomolecular interactions, such as protein–protein interactions. Fantin et al.  comparedLipids can influence the structure and function of membrane proteins. For example, while some oligomeric membrane proteins contain strongly bound inter-subunit interfaces, other weakly oligomerise and readily dissociate into monomers or lower oligomeric forms upon extraction from their native lipid environment. It has been suggested  that in Another interesting area of research is the interaction of membrane proteins with drugs or antibiotics. Using native MS, the antibiotic chlorhexidine was shown to induce a change in the oligomeric state of the chlorhexidine efflux pump AceI . Chlorhe+. Such ions have been previously shown to regulate the assembly of several membrane protein complexes [+ binding in the presence of antagonists and suppressed Na+ binding in the presence of agonists. This result is consistent with previous structural studies that showed the presence of an allosteric Na+ binding pocket in inactive conformations of Class A GPCRs, which is absent in the active conformations. For GCGR, a more stable conformation was observed in NaCl/Tris buffer compared to ammonium acetate, as indicated by the lower charge state distribution and enhanced binding of the stabilising negative allosteric modulator, NNC0666, observed in the former buffer. These results highlight the applicability of native MS to study membrane proteins from physiologically relevant salt buffers. More recently, another native MS approach was developed to interrogate the propensity of β1-adrenergic receptor coupling to Gs and Gi. Upon capturing the G-protein-coupling complexes in presence of different ligands, it was observed that endogenous zinc ions specifically stabilise the complexes between G-proteins and receptors. Overall, this study uncovered a novel role for metal ions in modulating the selectivity of G-protein coupling [One type of interaction that is challenging to observe by native MS is the binding of proteins to non-volatile salt ions, such as Naomplexes . In natiomplexes . Neverthomplexes . This apomplexes  to studycoupling .To probe the interactions with ligands, in one study Gray et al.  combinedWhen using even the most ‘native-like’ membrane mimetic, there is always a risk of experimental artefacts caused by the extraction of the protein from its native membrane environment. Recently, membrane proteins and their complexes have been released into the mass spectrometer directly from their native membrane, marking a significant shift towards native MS of membrane proteins in the most native-like contexts. In 2018, Chorev et al.  used natIn a very recent study, Chen et al.  ejected Despite the numerous advantages and a recently published protocol , the praNative MS is a versatile and rapid technique for obtaining non-covalent interactions of membrane proteins that are often difficult or outright intractable to other techniques. It can be used to study membrane proteins in a varied range of membrane mimetic systems, notably in their own native lipid bilayer. Advances in the synthesis and commercialisation of mild and native MS-compatible detergents will continue to be relevant for investigating protein–drug/lipid binding where highly purified samples are required. Increasing the repertoire of activation regimes that enables release of intact oligomers from lipid bilayer nanodiscs will allow selective disruptions of the nanodiscs with minimal dissociation of the encapsulated protein complexes. Such an advance will pave the way for releasing intact proteins from more complex biological membranes and tissues for which strong lipid–protein interactions must be overcome.Recent advances in native MS have enabled protein assemblies to be released from intact lens tissue . For sucIn the modern era of structural biology, native MS has emerged as a powerful tool for defining the molecular sociology of a variety of membrane protein targets including transporters, channels, and receptors. Starting off with detergents and membrane mimetics, this area of research is now going through a transformational period towards more native environments.Although still in its infancy, analysis of complexes directly from native membranes by native MS has already managed to capture several key signalling events. However, the full potential and widespread use of this approach are yet to happen.In addition to optimising sample preparation strategies, there is a clear need for new instrumentation, which combines sensitivity, dynamic mass range, resolution, and access to diverse ion activation techniques including HCD, ECD, ETD, IRMPD and UVPD.


Novel optical sensors, remote/proximal sensing , LiDAR, and automated analyses of below-ground development offer the possibility to infer plant physiological status and growth. However, there are limitations to such ‘indirect’ approaches to gauging plant physiology. These methodologies that are appropriate for the rapid high temporal screening of a number of crop varieties over a wide spatial scale do still require ‘calibration’ or ‘validation’ with direct empirical measurement of plant physiological status. The use of deep-learning and artificial intelligence approaches may enable the effective synthesis of large multivariate datasets to more accurately quantify physiological characters rapidly in high numbers of replicate plants. Advances in automated data collection and subsequent data processing represent an opportunity for plant phenotyping efforts to fully integrate fundamental physiological data into vital efforts to ensure food and agro-economic sustainability.Plant physiological status is the interaction between the plant genome and the prevailing growth conditions. Accurate characterization of plant physiology is, therefore, fundamental to effective plant phenotyping studies; particularly those focused on identifying traits associated with improved yield, lower input requirements, and climate resilience. Here, we outline the approaches used to assess plant physiology and how these techniques of direct empirical observations of processes such as photosynthetic CO Plant physiology is central to photosynthetic performance, growth, and resilience to abiotic stress ,2. Physi2 via photosynthesis, capability to counteract photo-oxidative stress, and the efficient uptake/use of water. Quantification of the photosynthetic, oxidative, and water status of plants requires detailed and time-consuming measurements by highly trained personnel. While it may not be possible to measure these attributes directly, many phenotyping approaches can indirectly infer or estimate these parameters rapidly. After outlining the traditional approaches to quantifying plant ecophysiology, we then describe the theoretical basis and application of rapid screening phenomic approaches that gauge plant ecophysiological status.Concerns regarding the pressures imposed by climate change, population growth, and the loss of productive agricultural land area has led to an expansion in plant phenomic research in recent years. However, the development of plant phenotyping has been impaired by a number of constraints at different scales: the ability to automate large numbers of morphological measurements at high temporal resolution, processing of large volumes of morphological/genetic data, and the capacity to perform detailed physiological analyses. Plant phenotyping efforts are focused towards the identification and development of more productive and climate resilient crop genotypes. Crop productivity and climate resilience are largely determined by the potential to assimilate CO2 uptake and transpiration  and [H2O] in the air entering and then exiting the cuvette after passing over the leaf are measured. The delta values of [CO2] and [H2O] are then used to calculate parameters such as photosynthesis (PN), stomatal conductance (Gs), and the internal sub-stomatal concentration of CO2 within the leaf (Ci), as shown in [2] outside the leaf (Ca), photosynthetic photon flux density (PPFD), temperature, relative humidity, leaf-to-air vapour pressure deficit, and velocity of air flow can be controlled within the leaf cuvette. This enables rapid manipulation of cuvette conditions to quantify responses to specific factors influencing photosynthesis and the exchange of gases between the leaf and the external atmosphere. Many plant photosynthesis systems also include the capacity to simultaneously measure chlorophyll fluorescence (ChlF) parameters alongside leaf gas exchange. Plant photosynthetic leaf gas exchange systems utilize infra-red gas analyzers to quantify fluxes of COshown in  and the Ca, and leaf-to-air vapour pressure deficit are utilized within the leaf cuvette, each leaf requires a period of time to adjust to those cuvette conditions, precluding the ability to take large numbers of measurements at the same time/conditions in phenotyping trials of multiple genotypes. Less time-consuming instantaneous point measurements of leaf gas exchange parameters can be performed without using controlled cuvette conditions. Such measurements where PPFD and temperature track ‘ambient’ conditions do not require the same adjustment period for the leaf, but variations in ambient conditions, diminishes comparability between measurements, and may render any phenotypic or treatment effect indiscernible    .PN–Ci curve characteristic of a C3 plant Michaelis–Menten enzymatic reaction. Photosynthesis is limited by the availability of CO2 at the initial part of the curve, and this represents the maximum rate of carboxylation of ribulose-1,5-bisphosphate carboxylase/oxygenase (RubisCO) (Vcmax). At higher levels of [CO2], PN is no longer limited by substrate availability, but the regeneration of ribulose-1,5-bisphosphate (RuBP) (Jmax). The parameters Vcmax and Jmax are critical components of crop and climate models  in the leaf cuvette and dynamically measure the concurrent effect on PN. These response curves are known as RACiR curves, standing for “Rapid A-Ci Response”  ramping speed between varieties) , chemical signals of drought, or leaf-to air vapour pressure deficit enables quantification of stomatal physiological responsiveness /[R680 + R430]), structural insensitive pigment index (SIPI = [R800 − R445]/[R800 − R680]), or simple pigment ratio index (SRPI = R430/R680) /[R531 + R570]) also gauges carotenoid–chlorophyll ratios, and the short-term de-epoxidation state of the xanthophyll cycle ) )  correlat/R1455]) .Foliar water content is important in plant responses to salinity and monitoring the vegetation fire risk. The WI is sensitive to salinity stress in barley . A numbeRED) and near-infrared (RNIR) wavelength bands [NIR/RRED]/[RNIR + RRED]) quantifies the difference between visible and near-infrared reflectance to gauge the amount of green vegetation cover over an area of land . A. A157]. Vcmax Jmax, chlorophyll content, and nitrogen concentration for several species of plant from maize [Partial least square regression  is curreom maize  to tropiom maize . For a mom maize  and Grzyom maize .The variables combined during partial least square regression represent a latent feature that acts as intermediary input data to a successive linear regression. An interesting feature of the partial least square regression approach relies on the capacity to interpret directly the feature learnt through the computed weight, also called ‘loading values’ in this case. These values may identify a direct link between the reflectance combination and the specific indicator of plant physiological status . Other standard machine learning methods such as support vector machine, artificial neural networks, or random forest have, to a lesser degree, been employed for plant phenotyping, but mainly in the classification of plant biotic stress (for a more detailed review see ).Deep learning is a machine learning technique that attempts to tackle the problem of the transferability of the features learned to different contexts such as crop species, climate, or agricultural treatments. As in partial least square regression, these models learn internal features but the number of layers is significantly larger. We may visualize a deep learning model as a stack of multiple layers of single machine learning models, where each succeeding layer uses the output from the previous layer as input. As the number of stacked layers increase, the features learned can then be generalized to more diverse contexts . Such meIn particular, a deep convolutional neural network (DCNN) is an appropriate method to deal with image data, since the connection between the layers is structured to extract spatially local features . Hence, The abstractions reached by deep learning models expand their applications over the class or value estimation. For instance, generative adversarial networks have also been used in plant phenotyping for data augmentation . Instead2 may enable more rapid assessment of photosynthetic, photorespiratory, and metabolic respiratory fluxes of carbon. Future technological developments in LED and sensor technologies will improve the availability, expand the application, and reduce the costs of plant phenotyping and digital agriculture technologies. Partial least squares regression, deep-learning, and artificial intelligence technologies may enable the use of multi-variate data sources to accurately infer plant physiological performance. The rapidly developing nature of these technologies may alleviate the ‘physiological bottleneck’ that has constrained the application of phenotyping efforts to enhance future food security in a hotter drier world.Plant physiological function forms the basis of productivity and resilience to abiotic stress. Traits such as the rate of photosynthesis, the capacity to dissipate excess energy, protective antioxidants, stomatal control, and the uptake of water/nutrients are central to plant growth rate, tolerance to abiotic stress, and water/nutrient usage. The characterization of physiological attributes associated with desirable traits is essential to successful plant phenotyping, to identify and then develop crop varieties with higher yields, lower input requirements , and improved climate resilience. However, phenotyping efforts are constrained by the difficulties associated with accurate direct measurement of plant physiological processes, specifically those related to photosynthetic leaf gas exchange, ChlF, plant water relations, and below-ground processes. The use of low-cost optical sensors, remote/proximal sensing of spectral reflectance, SiF, and LiDAR offers the potential to rapidly assess plant physiological status at high temporal resolution over wide spatial scales. However, given the indirect nature of many of these measurements, empirical physiological data are still a necessity. Developments in leaf gas exchange technologies such as the integration of carbon isotopic analysis of CO