Combining Bayesian optimization and automation to simultaneously optimize reaction conditions and routes.

Reaching optimal reaction conditions is crucial to achieve high yields, minimal by-products, and environmentally sustainable chemical reactions. With the recent rise of artificial intelligence, there has been a shift from traditional Edisonian trial-and-error optimization to data-driven and automated approaches, which offer significant advantages. Here, we showcase the capabilities of an integrated platform; we conducted simultaneous optimizations of four different terminal alkynes and two reaction routes using an automation platform combined with a Bayesian optimization platform. Remarkably, we achieved a conversion rate of over 80% for all four substrates in 23 experiments, covering ca. 0.2% of the combinatorial space. Further analysis allowed us to identify the influence of different reaction parameters on the reaction outcomes, demonstrating the potential for expedited reaction condition optimization and the prospect of more efficient chemical processes in the future.

Exploring perceptions of self-stigma of substance use and current alcohol and marijuana use patterns among college students.

BACKGROUND: While research has examined the effect of stigma from others towards individuals with substance use disorders, few studies have examined the relationship between perceived self-stigma and engagement in substance use more broadly, especially among non-clinical samples. AIMS: The present study examined the relationships between perceptions of self-stigma if one were to develop a substance use disorder, consisting of negative self-esteem and negative self-efficacy, and alcohol or marijuana use behaviors and outcomes. METHOD: Participants (n = 2,243; 71.5% female) were college students within the U.S. recruited to participate in an online survey on substance use with a special focus on alcohol and marijuana. RESULTS: Results indicated no significant differences in stigma scores across individuals with different lifetime alcohol and marijuana use. Stigma ratings did differ between individuals with different profiles of last 30-day alcohol and marijuana use where, generally, individuals with lifetime use but no use in the last 30-day reported higher levels of self-stigma. Correlation analyses indicated that perceived impact of substance use disorder on sense of self-efficacy and self-esteem related negatively to nearly all observed factors of alcohol and marijuana use. CONCLUSIONS: Though self-stigma, and stigma more broadly, has been shown to have negative implications for people with substance use disorders, the present study suggests that for non-clinical populations there may be some protective association between perceived self-stigma and alcohol or marijuana use engagement. This is not to say that self-stigma is a positive clinical intervention. Rather, we interpret these findings to indicate that negative perceptions of substance use disorder on the sense of self may be associated with distinct alcohol and marijuana use behaviors among young adults.

A multidisciplinary approach to analyze the antimicrobial resistance in natural ecosystems.

Antimicrobial Resistance (AMR) poses a global threat to both human health and environmental well-being. Our study delved into Costa Rican wildlife reserves, uncovering a substantial human impact on these ecosystems and underscoring the imperative to pinpoint AMR hotspots. Embracing a One Health perspective, we advocated for a comprehensive landscape analysis that intricately intertwined geographic, climatic, forest, and human factors. This study illuminated the link between laboratory results and observed patterns of antimicrobial use, thereby paving the way for sustainable solutions. Our innovative methodology involved deploying open-ended questions to explore antimicrobial usage across livestock activities, contributing to establishing a comprehensive methodology. Non-invasive sampling in wildlife emerged as a critical aspect, shedding light on areas contaminated by AMR. Feline species, positioned at the apex of the food chain, acted as sentinels for environmental health due to heightened exposure to improperly disposed waste. Regarding laboratory findings, each sample revealed the presence of at least one antimicrobial resistance gene (ARG). Notably, genes encoding resistance to tetracyclines dominated (94.9%), followed by beta-lactams (75.6%), sulfonamides (53.8%), aminoglycosides (51.3%), quinolones (44.9%), phenicols (25.6%), and macrolides (20.5%). Genes encoding polymyxins were not detected. Moreover, 66% of samples carried a multi-resistant microbiome, with 15% exhibiting resistance to three antimicrobial families and 51% to four. The absence of a correlation between forest coverage and ARG presence underscored the profound human impact on wildlife reserves, surpassing previous estimations. This environmental pressure could potentially modify microbiomes and resistomes in unknown ways. As not all antimicrobial families encoding ARGs were utilized by farmers, our next step involved evaluating other human activities to identify the primary sources of contamination. This comprehensive study contributed crucial insights into the intricate dynamics of AMR in natural ecosystems, paving the way for targeted interventions and sustainable coexistence.

Characterisation of paediatric brain tumours by their MRS metabolite profiles.

1H-magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single-voxel MRS (point-resolved single-voxel spectroscopy sequence, 1.5 T: echo time [TE] 23-37 ms/135-144 ms, repetition time [TR] 1500 ms; 3 T: TE 37-41 ms/135-144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann-Whitney U-tests and Kruskal-Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours.

Printed graphene and its composite with copper for electromagnetic interference shielding applications.

Advances in mobile electronics and telecommunication systems along with 5G technologies have been escalating the electromagnetic interference (EMI) problem in recent years. Graphene-based material systems such as pristine graphene, graphene-polymer composites and other graphene-containing candidates have been shown to provide adequate EMI shielding performance. Besides achieving the needed shielding effectiveness (SE), the method of applying the candidate shielding material onto the object in need of protection is of enormous importance due to considerations of ease of application, reduced logistics and infrastructure, rapid prototyping and throughput, versatility to handle both rigid and flexible substrates and cost. Printing readily meets all these criteria and here we demonstrate plasma jet printing of thin films of graphene and its composite with copper to meet the EMI shielding needs. SE over 30 dB is achieved, which represents blocking over 99.9% of the incoming radiation. Graphene and its composite with copper yield higher green index compared to pure copper shields, implying reduced reflection of incoming electromagnetic waves to help reduce secondary pollution.

Systemic health effects of noise exposure.

Noise, any unwanted sound, is pervasive and impacts large populations worldwide. Investigators suggested that noise exposure not only induces auditory damage but also produces various organ system dysfunctions. Although previous reviews primarily focused on noise-induced cardiovascular and cerebral dysfunctions, this narrow focus has unintentionally led the research community to disregard the importance of other vital organs. Indeed, limited studies revealed that noise exposure impacts other organs including the liver, kidneys, pancreas, lung, and gastrointestinal tract. Therefore, the aim of this review was to examine the effects of noise on both the extensively studied organs, the brain and heart, but also determine noise impact on other vital organs. The goal was to illustrate a comprehensive understanding of the systemic effects of noise. These systemic effects may guide future clinical research and epidemiological endpoints, emphasizing the importance of considering noise exposure history in diagnosing various systemic diseases.

Quiste meniscal posterior a la sutura meniscal con monofilamento de polipropileno / Meniscal cyst after polypropylene monofilament suture

Introducción: la función del tejido meniscal es fundamental en la transmisión y distribución de cargas de la rodilla. En casos de lesión meniscal, la sutura es el tratamiento quirúrgico de elección, y pueden utilizarse diferentes materiales para realizarla. El objetivo del trabajo es analizar la aparición de quistes meniscales sintomáticos con el uso de sutura no reabsorbible del tipo monofilamento de polipropileno en un grupo de pacientes con lesiones en asa de balde y evaluar el material de sutura como causal de quiste.Materiales y métodos: se realizó un estudio retrospectivo de un grupo de pacientes con lesiones en asa de balde suturadas con material no reabsorbible del tipo monofilamento de polipropileno (MP) y sutura de alta resistencia de polietileno de ultra alto peso molecular UHMWPE (SAR) y se analizó la presencia de quiste meniscal sintomático como complicación. Los criterios de inclusión para este estudio fueron pacientes con lesiones en asa de balde a los cuales se les realizó sutura meniscal con técnicas combinadas con material de tipo no reabsorbible. Se excluyeron pacientes con lesiones que no fueran con patrón en asa de balde o a los cuales se les hizo sutura meniscal todo-adentro únicamente.Resultados: un total de veinticinco pacientes, quince de sexo masculino y diez de sexo femenino. La edad media del grupo evaluado fue de 27.8 años. El 72% fue suturado con sutura de alta resistencia (SAR) mientras que a un 28% se les realizó sutura con monofilamento de polipropileno (MP). El 92% de las lesiones se presentaron en el menisco interno. Se observaron tres pacientes con quistes meniscales sintomáticos asociados a la sutura MP, los cuales fueron tratados quirúrgicamente con buena evolución. Conclusión: identificamos en nuestra serie que la aparición de quistes sintomáticos se relaciona estrechamente con el uso de monofilamento de polipropileno (MP). Consideramos la utilización de hilos no reabsorbibles de alta resistencia (polietileno de ultra alto peso molecular UHMWPE) como la primera opción para realizar las suturas meniscales por la baja tasa de complicación y los buenos resultados. Nivel de Evidencia: IV

Introduction: The function of the meniscal tissue is fundamental in the transmission and distribution of knee loads. In cases of meniscal injury, suturing is the surgical treatment of choice, and different materials can be used to perform it. The aim of the work is to analyze the appearance of symptomatic meniscal cysts with the use of non-absorbable polypropylene monofilament suture in a group of patients with bucket handle injuries and to evaluate the suture material as a cause of the cyst. Materials and methods: a retrospective study was carried out on a group of patients with bucket-handle injuries sutured with non-absorbable polypropylene monofilament (MP) material and high-strength ultra-high molecular weight UHMWPE polyethylene (SAR) suture and the presence of a symptomatic meniscal cyst as a complication was analyzed. The inclusion criteria for this study were patients with bucket-handle injuries in whom meniscal suture was performed with combined techniques with non-resorbable material. Patients with injuries other than a bucket-handle pattern or who underwent all-in meniscal suturing only were excluded.Results: a total of twenty-five patients, fifteen males and ten females. The average age of the evaluated group was 27.8 years. 72% were sutured with high resistance suture (SAR) while 28% were sutured with polypropylene monofilament (MP). 92% of the injuries occurred in the medial meniscus. Three patients were observed with symptomatic meniscal cysts associated with the MP suture, which were treated surgically with good outcomes. Conclusion: we identified in our series that the appearance of symptomatic cysts is closely related to the use of polypropylene monofilament (MP). We consider the use of high-strength non-absorbable threads (ultra-high molecular weight polyethylene UHMWPE) as the first option to perform meniscal sutures due to the low complication rate and good results. Level of Evidence: IV

How to Accelerate R&D and Optimize Experiment Planning with Machine Learning and Data Science.

Accelerating R&D is essential to address some of the challenges humanity is currently facing, such as achieving the global sustainability goals. Today's Edisonian approach of trial-and-error still prevalent in R&D labs takes up to two decades of fundamental and applied research for new materials to reach the market. Turning around this situation calls for strategies to upgrade R&D and expedite innovation. By conducting smart experiment planning that is data-driven and guided by AI/ML, researchers can more efficiently search through the complex - often constrained - space of possible experiments and find or hit the global optima much faster than with the current approaches. Moreover, with digitized data management, researchers will be able to maximize the utility of their data in the short and long terms with the aid of statistics, ML and visualization tools. In what follows, we describe a framework and lay out the key technologies to accelerate R&D and optimize experiment planning.

Mpox "Monkeypox" Virus: The Importance of Inclusive Imagery to Prevent Disease Stigma.

Since the initial coverage of the monkeypox virus, there has been debate among physicians over how to responsibly communicate public health information without harming historically marginalized communities. On November 28, 2022, the World Health Organization (WHO) announced its plan to rename monkeypox "mpox" following growing concern regarding the stigmatizing nature of the disease's original name. We believe providers, and especially dermatologists, have an opportunity to further shape conversations about the virus to mitigate the same stigmas that were perpetuated by media coverage surrounding the HIV epidemic and contributed to the rise of anti-LGBTQ and HIV+ violence. Specifically, dermatologists have an opportunity to engage in conversations about the psychosocial impact of visible skin disease, advocating for healthcare equity by using both inclusive imagery and non-discriminatory language.J Drugs Dermatol. 2023;22(12):1235-1236. doi:10.36849/JDD.7482.

Reposicionamiento Labial. Caso Clínico

El reposicionamiento labial es un procedimiento quirúrgico mínimamente invasivo que se utiliza para tratar una sonrisa gingival, la cual, es una afección en la que una cantidad significativa de la encía queda expuesta cuando una persona sonríe y puede deberse a una variedad de factores, como un exceso de tejido gingival, un labio superior corto o músculos hiperactivos del labio superior, entre otros. El alargamiento clínico de la corona, por otro lado, consiste en eliminar el exceso de tejido gingival y, si es necesario, el tejido óseo para exponer una mayor parte de la corona natural del diente. Se reporta un caso clínico de paciente femenino de 31 años que presentó una sonrisa gingival provocada por hipermovilidad de labio superior y un exceso de tejido gingival localizado. El plan de tratamiento involucró una combinación de reposicionamiento labial y alargamiento de corona. Los resultados estéticos fueron significativos, con la sonrisa del paciente más equilibrada y proporcionada. Se redujo la cantidad de tejido gingival expuesto cuando la paciente sonreía y la longitud de los dientes fue más visible, lo que dio como resultado una sonrisa de aspecto más natural, además de aumentar su aceptación al sonreír.

SUMMARY: Lip repositioning is a minimally invasive surgical procedure used to treat a gummy smile, which is a condition in which a significant amount of the gum is exposed when a person smiles and may be due to a variety of factors, such as excess gum tissue, a short upper lip or overactive muscles of the upper lip, among others. Clinical crown lengthening, on the other hand, involves removing excess gingival tissue and, if necessary, bone tissue to expose more of the natural crown of the tooth. Clinical case: A clinical case of a 31-year-old female patient who presented a gummy smile caused by hypermobility of the upper lip and an excess of localized gingival tissue is reported. The treatment plan involved a combination of lip repositioning and crown lengthening. The aesthetic results were significant, with the patient's smile more balanced and displayed. The amount of the patient's exposed gum tissue when smiled was reduced and the length of the teeth was more visible, resulting in a more natural-looking smile, as well as increasing their acceptance of smiling.

Mechanical-acoustical analogy: From laboratory to home during the COVID-19 pandemic.

A clear comprehension of the oscillatory nature of sound for acoustics undergraduate students is of paramount importance. In this paper, two online experiments were implemented to aid teaching of the oscillatory nature of sound through the analogy between a mechanical mass-spring model and a Helmholtz resonator. The study was conducted among undergraduate students taking a science course in the Electronic and Electrical Engineering career curriculum. These in-class experiments were conducted during the COVID-19 pandemic via the Zoom platform. Students measured the Helmholtz resonant frequency of a plastic bottle with a smartphone application and compared its oscillatory behavior with that of a conventional harmonic oscillator under a professor-student collaborative environment. The results of this study suggest that, with careful experiment design, students can effectively benefit from the use of common technology tools, which, in turn, poses these methodologies as a rather satisfactory alternative to face-to-face laboratory sessions.

PLIN5 interacts with FATP4 at membrane contact sites to promote lipid droplet-to-mitochondria fatty acid transport.

Cells adjust their metabolism by remodeling membrane contact sites that channel metabolites to different fates. Lipid droplet (LD)-mitochondria contacts change in response to fasting, cold exposure, and exercise. However, their function and mechanism of formation have remained controversial. We focused on perilipin 5 (PLIN5), an LD protein that tethers mitochondria, to probe the function and regulation of LD-mitochondria contacts. We demonstrate that efficient LD-to-mitochondria fatty acid (FA) trafficking and ß-oxidation during starvation of myoblasts are promoted by phosphorylation of PLIN5 and require an intact PLIN5 mitochondrial tethering domain. Using human and murine cells, we further identified the acyl-CoA synthetase, FATP4 (ACSVL4), as a mitochondrial interactor of PLIN5. The C-terminal domains of PLIN5 and FATP4 constitute a minimal protein interaction capable of inducing organelle contacts. Our work suggests that starvation leads to phosphorylation of PLIN5, lipolysis, and subsequent channeling of FAs from LDs to FATP4 on mitochondria for conversion to fatty-acyl-CoAs and subsequent oxidation.

Sustaining Recovery: What Does it Take to Remain in Long-term Recovery?

Background: Understanding the complexities of establishing and sustaining recovery from substance addiction and the dynamic individual processes that occur will assist addiction treatment professionals in fostering sustained recovery behavior in clients. With the estimated 22 million individuals in recovery from addiction in the United States, this exploration is timely and extends our understanding of recovery. Objectives: The objective of the study was to answer the research question: "What do individuals in recovery identify as their primary needs throughout the process of recovery from substance use?" Results: 403 adults in early, middle and late stages of recovery from drugs or alcohol and were asked to write in-depth responses to questions about factors leading to their recovery. Content analysis revealed several major themes: a) relationships, b) recovery community, c) thriving, d) goal-focused, e) people, places, and things, f) recovery tools, g) professional support, h) rock bottom, and i) abstinence. Chi-square analyses indicated that the recovery stage is significantly associated with what participants reported they believe they need to sustain recovery. Radial charts depict recovery community is a more reported needed factor for participants in long-term recovery than in early recovery. Conclusions: The results of this study highlight differences in the experiences of those in early recovery and those in late recovery. This demonstrates the dynamic nature of the recovery process and informs addiction treatment professionals of the multidimensional nature of recovery.

Risk of Radiation Dermatitis in Patients With Skin of Color Who Undergo Radiation to the Breast or Chest Wall With and Without Regional Nodal Irradiation.

PURPOSE: Acute radiation dermatitis (ARD) is common after radiation therapy for breast cancer, with data indicating that ARD may disproportionately affect Black or African American (AA) patients. We evaluated the effect of skin of color (SOC) on physician-reported ARD in patients treated with radiation therapy. METHODS AND MATERIALS: We identified patients treated with whole breast or chest wall ± regional nodal irradiation or high tangents using 50 Gy in 25 fractions from 2015 to 2018. Baseline skin pigmentation was assessed using the Fitzpatrick scale (I = light/pale white to VI = black/very dark brown) with SOC defined as Fitzpatrick scale IV to VI. We evaluated associations among SOC, physician-reported ARD, late hyperpigmentation, and use of oral and topical treatments for RD using multivariable models. RESULTS: A total of 325 patients met eligibility, of which 40% had SOC (n = 129). On multivariable analysis, Black/AA race and chest wall irradiation had a lower odds of physician-reported grade 2 or 3 ARD (odds ratio [OR], 0.110; 95% confidence interval [CI], 0.030-0.397; P = .001; OR, 0.377; 95% CI, 0.161-0.883; P = .025), whereas skin bolus (OR, 8.029; 95% CI, 3.655-17.635; P = 0) and planning target volume D0.03cc (OR, 1.001; 95% CI, 1.000-1.001; P = .028) were associated with increased odds. On multivariable analysis, SOC (OR, 3.658; 95% CI, 1.236-10.830; P = .019) and skin bolus (OR, 26.786; 95% CI, 4.235-169.432; P = 0) were associated with increased odds of physician-reported late grade 2 or 3 hyperpigmentation. There was less frequent use of topical steroids to treat ARD and more frequent use of oral analgesics in SOC versus non-SOC patients (43% vs 63%, P < .001; 50% vs 38%, P = .05, respectively). CONCLUSIONS: Black/AA patients exhibited lower odds of physician-reported ARD. However, we found higher odds of late hyperpigmentation in SOC patients, independent of self-reported race. These findings suggest that ARD may be underdiagnosed in SOC when using the physician-rated scale despite this late evidence of radiation-induced skin toxicity.

Invaginación Apendicular en preescolar: Reporte de un caso y revisión de la literatura / Appendicular invagination in a pre-school child; a case-report and literature review

La invaginación intestinal sucede cuando un segmento del intestino se introduce en otro. La presentación apendicular es menos común, afectando principalmente a lactantes. Frecuentemente, se comprueba durante el intraoperatorio. El tratamiento es la desinvaginación, seguido de la exéresis del apéndice. De no lograrse, se prefiere la resección amplia o una hemicolectomía derecha. Se presenta en caso de una niña de 4 años que acudió por dolor abdominal, hiporexia, vómitos y sensación de alza térmica; la ecografía mostró conglomeración de asas intestinales e imagen redondeada. En cirugía se encontró invaginación apendicular que compromete el ciego, se resecó la masa hasta el inicio del colon ascendente. Se realizó una ileostomía sin fístula mucosa; el estudio anatomo-patológico informó necrosis del apéndice cecal. Tres meses después se restituyó el tránsito intestinal. La Intususcepción apendicular tiene síntomas inespecíficos. En Perú, puede llegar a ser mortal. Una historia clínica detallada con evaluación minuciosa ofrece un acertado diagnóstico y un tratamiento oportuno.

SUMMARY Intestinal invagination occurs when an intestinal segment is introduced into another segment. The appendicular presentation is less common and affects predominantly infants. The diagnosis is corroborated during the surgical intervention which consists of de-invagination followed by surgical removal of the appendix, if the latter is not possible then a wide resection or right hemicolectomy is indicated. We present the case of a 4-year-old girl who attended with a history of abdominal pain, anorexia, vomiting and fever; an abdominal ultrasound showed intestinal agglomeration and a rounded mass. The surgical findings included appendicular invagination that affected the cecum, the lesion was resected until the ascending colon. An ileostomy was performed, the anatomopathological findings indicated necrosis of the appendix. Three months later the normal intestinal transit was restored. Appendicular intussusception has non-specific symptoms and could be mortal in Peru. A detailed clinical history may help in diagnosing and offering proper treatment.