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This study examined hybrid steel-concrete composite beams with flat and corrugated webs constructed from various steels for shear strength. Also examined the thickness and direction of double corrugated web. Six simply supported composite beams, each measuring 2000 mm in length, were constructed with concrete slabs measuring 350*70 mm and high-strength steel flanges measuring 80*6 mm. Three groups were divided according to web; the first group had two beams with carbon web (flat and corrugated), and the second group was the same as group one, but the web was galvanized. The last group consists of two beams with two corrugated galvanized webs that differ in their direction. The groups tested under two-point loads to check shear strength. From the result, three comparisons were made, according to the web’s material, that shear strength for carbon is better than galvanized in 50% and 42% for flat and corrugated, respectively. In terms of the corrugations’ shape, the corrugated web increased load capacity by 4.4% and 22% over the flat web in the first and second groups. The last comparison done on the direction of corrugated webs, the beam with two opposite corrugations increased shear strength by 4% more than the same-direction beam. To summarize it all, carbon is better than galvanized. Two equal-thick corrugated layers are stronger than one flat of the same thickness and improve its behavior.

Cutaneous melanoma tumors are heterogeneous and show diverse responses to treatment. Identification of robust molecular biomarkers for classifying melanoma tumors into clinically distinct and homogenous subtypes is crucial for improving the diagnosis and treatment of the disease. In this study, we present a classification of melanoma tumors into four subtypes with different survival profiles based on three distinct gene expression signatures: keratin, immune, and melanogenesis. The melanogenesis expression pattern includes several genes that are characteristic of the melanosome organelle and correlates with worse survival, suggesting the involvement of melanosomes in melanoma aggression. We experimentally validated the secretion of melanosomes into surrounding tissues by melanoma tumors, which potentially affects the lethality of metastasis. We propose a simple molecular decision tree classifier for predicting a tumor’s subtype based on representative genes from the three identified signatures. Key predictor genes were experimentally validated on melanoma samples taken from patients with varying survival outcomes. Our three-pattern approach for classifying melanoma tumors can contribute to advancing the understanding of melanoma variability and promote accurate diagnosis, prognostication, and treatment.

Bisphenol S (BPS) is a structural analog of the endocrine disruptor bisphenol A (BPA); it is the main BPA replacement in the plastics industry. Previous studies have shown that BPA and BPS exhibit similar effects on reproduction in fish and rodent species. BPS reportedly alters steroidogenesis in bovine granulosa cells. Luteinised granulosa cells collected from 59 women who were undergoing an in vitro fertilization procedure were cultured for 48 h in the presence or absence of BPS (10 nM, 100 nM, 1 µM, 10 µM or 50 µM). BPS exposure was investigated by assessing follicular fluids from these 59 women for their BPS content. Culture medium, cells, total messenger RNA (mRNA) and total protein extracted from the luteinised granulosa cells were examined for oestradiol and progesterone secretion, cellular proliferation, viability, gene expression, steroidogenic enzyme expression and cell signaling. BPS was measured in follicular fluids using mass spectrometry. Exposure of granulosa cells to 10 or 50 µM BPS for 48 h induced a 16% (p = 0.0059) and 64% (p < 0.0001) decrease, respectively, in progesterone secretion; 50 µM BPS decreased oestradiol secretion by 46% (p < 0.0001). Ten µM BPS also tended to reduce CYP11A1 protein expression by 37% (p = 0.0947) without affecting HSD3B1 and CYP19A1 expression. Fifty µM BPS increased ERRγ expression. Environmental levels of BPS (nanomolar range) did not induce changes in steroidogenesis in human granulosa cells. The effects of BPS were observed after only 48 h of BPS exposure. These acute effects might be similar to chronic effects of physiological BPS levels.

In oncology, the expanding use of multi-gene panels to explore familial cancer predisposition and tumor genome analysis has led to increased secondary findings discoveries (SFs) and has given rise to important medical, ethical, and legal issues. The American College of Medical Genetics and Genomics published a policy statement for managing SFs for a list of genes, including 25 cancer-related genes. Currently, there are few recommendations in Europe. From June 2016 to May 2017, the French Society of Predictive and Personalized Medicine (SFMPP) established a working group of 47 experts to elaborate guidelines for managing information given on the SFs for genes related to cancers. A subgroup of ethicists, lawyers, patients’ representatives, and psychologists provided ethical reflection, information guidelines, and materials (written consent form and video). A subgroup with medical expertise, including oncologists and clinical and molecular geneticists, provided independent evaluation and classification of 60 genes. The main criteria were the “actionability” of the genes (available screening or prevention strategies), the risk evaluation (severity, penetrance, and age of disease onset), and the level of evidence from published data. Genes were divided into three classes: for class 1 genes (n = 36), delivering the information on SFs was recommended; for class 2 genes (n = 5), delivering the information remained questionable because of insufficient data from the literature and/or level of evidence; and for class 3 genes (n = 19), delivering the information on SFs was not recommended. These guidelines for managing SFs for cancer-predisposing genes provide new insights for clinicians and laboratories to standardize clinical practices.

Purpose To compare the outcomes of distal neurotomy (DN) versus proximal neurotomy (PN) for the surgical management of painful neuromas in amputees and non-amputees, whether used in passive or active treatment. Methods A retrospective study was conducted on patients who underwent surgery for painful traumatic neuromas between 2019 and 2022. DN with neuroma excision was performed at the level of the injury or amputation. PN was performed using a separate proximal approach without neuroma excision. Outcomes included a Numerical Rating Scale (NRS) score and Patient-Reported Outcomes Measurement Information System (PROMIS) scores, as well as patients’ subjective assessments. Results A total of 33 patients were included: 17 amputees and 16 non-amputees. They totalized 43 neuromas treated by DN in 21 cases and PN in 22 cases. At the median follow-up time of 13 months, there were significant decreases in all NRS and PROMIS scores in the whole series. The decrease in limb pain scores was not significantly different between groups, except for the decrease in pain interference and patient satisfaction which were higher in the DN group. Sub-group analyses found the same significant differences in amputees. Targeted muscle reinnervation (TMR) was associated with a higher decrease in PROMIS scores. Conclusion DN seemed to give better results in amputees but there were confusing factors related to associated lesions. In other situations, the non-inferiority of PN was demonstrated. PN could be of interest for treating neuromas of superficial sensory nerves, for avoiding direct revision of a well-fitted stump and in conjunction with TMR.

Background Pregnancy is a period of transition with important physical and emotional changes. Even in uncomplicated pregnancies, these changes can affect the quality of life (QOL) of pregnant women, affecting both maternal and infant health. The objectives of this study were to describe the quality of life during uncomplicated pregnancy and to assess its associated socio-demographic, physical and psychological factors in developed countries. Methods A systematic review was performed according to the PRISMA guidelines. Searches were made in PubMed, EMBASE and BDSP (Public Health Database). Two independent reviewers extracted the data. Countries with a human development index over 0.7 were selected. The quality of the articles was evaluated on the basis of the STROBE criteria. Results In total, thirty-seven articles were included. While the physical component of QOL decreased throughout pregnancy, the mental component was stable and even showed an improvement during pregnancy. Main factors associated with better QOL were mean maternal age, primiparity, early gestational age, the absence of social and economic problems, having family and friends, doing physical exercise, feeling happiness at being pregnant and being optimistic. Main factors associated with poorer QOL were medically assisted reproduction, complications before or during pregnancy, obesity, nausea and vomiting, epigastralgia, back pain, smoking during the months prior to conception, a history of alcohol dependence, sleep difficulties, stress, anxiety, depression during pregnancy and sexual or domestic violence. Conclusions Health-related quality of life refers to the subjective assessment of patients regarding the physical, mental and social dimensions of well-being. Improving the quality of life of pregnant women requires better identification of their difficulties and guidance which offers assistance whenever possible.

Reciprocal deletion and duplication of the 16p11.2 region is the most common copy number variation (CNV) associated with autism spectrum disorders. We generated cortical organoids from skin fibroblasts of patients with 16p11.2 CNV to investigate impacted neurodevelopmental processes. We show that organoid size recapitulates macrocephaly and microcephaly phenotypes observed in the patients with 16p11.2 deletions and duplications. The CNV dosage affects neuronal maturation, proliferation, and synapse number, in addition to its effect on organoid size. We demonstrate that 16p11.2 CNV alters the ratio of neurons to neural progenitors in organoids during early neurogenesis, with a significant excess of neurons and depletion of neural progenitors observed in deletions. Transcriptomic and proteomic profiling revealed multiple pathways dysregulated by the 16p11.2 CNV, including neuron migration, actin cytoskeleton, ion channel activity, synaptic-related functions, and Wnt signaling. The level of the active form of small GTPase RhoA was increased in both, deletions and duplications. Inhibition of RhoA activity rescued migration deficits, but not neurite outgrowth. This study provides insights into potential neurobiological mechanisms behind the 16p11.2 CNV during neocortical development.

There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require programming skills. Here we present iLINCS ( http://ilincs.org ), an integrative web-based platform for analysis of omics data and signatures of cellular perturbations. The platform facilitates mining and re-analysis of the large collection of omics datasets (>34,000), pre-computed signatures (>200,000), and their connections, as well as the analysis of user-submitted omics signatures of diseases and cellular perturbations. iLINCS analysis workflows integrate vast omics data resources and a range of analytics and interactive visualization tools into a comprehensive platform for analysis of omics signatures. iLINCS user-friendly interfaces enable execution of sophisticated analyses of omics signatures, mechanism of action analysis, and signature-driven drug repositioning. We illustrate the utility of iLINCS with three use cases involving analysis of cancer proteogenomic signatures, COVID 19 transcriptomic signatures and mTOR signaling. There are only a few platforms that integrate multiple omics data types, bioinformatics tools, and interfaces for integrative analyses and visualization that do not require programming skills. Here the authors present an integrative web-based platform for analysis of omics data and signatures of cellular perturbations.

To describe the epidemiology and patterns of gymnastics-related Head & Neck trauma injuries using the NEISS database from 2001 to 2020. Cross-sectional analysis of a national database. Gymnastics-related ED visits between 2001 and 2020 were queried from the NEISS database. Bivariate chi-squared analyses were used to compare injury demographics, location, type, and disposition. Fracture location was identified using the narrative description of each case and were divided into subtypes for further analysis. 1455 gymnastics-related head and neck traumatic injuries were identified. The majority were in females (65.8%). The most common presenting age group was pediatric (≤18 years) (92.7%), and the largest racial group was Caucasian (51.5%). Of all location subtypes, facial injuries were the most common presenting injury type overall (45.2%). Regarding injury types, lacerations were most common (36.8%), followed by dental injury (30.7%) and fractures (21.2%). The most common location of head and neck fractures was the nose (45.8%), followed by cervical spine (16.7%) and orbit (13.3%). The majority (95.7%) of gymnastics-related head and neck traumatic injuries presenting to the ED were treated and discharged. This study characterizes gymnastics-related head and neck injuries which is a topic that is under-studied. The findings from this study are helpful for gymnasts and those who care for them including providers, coaches and guardians, and this data may help inform future guidelines for treatment and injury prevention.

Purpose Transdisciplinarity has been described as a fusion of theories, methods, and expertise across disciplinary boundaries to address complex, global problems. This approach has coincided with an increase in US medical schools offering masters degrees along with an MD degree to equip medical students to practice in complex, interconnected health systems. This study focused on medical schools that graduate the most dual degree students per year and explored the alignment of such programs with a transdisciplinary approach. Methods We identified 19 allopathic medical schools that annually graduated an average of 10 or more dual-degree students from 2015–2020. We surveyed these schools and asked participants to describe the reason(s) their institutions offered dual-degree programs. Two authors coded the narrative responses from the survey. Results Responses were received from 17 of the 19 schools. The analysis of participants’ responses regarding their institutions’ purpose for offering dual programs revealed several themes associated with a transdisciplinar y approach to training. The most common themes were expand skill sets beyond a medical degree (73%), provide opportunity for interdisciplinary collaboration (67%), expand career interest and goals (60%), develop leaders (53%), enhance residency applications (47%) and further the institution’s vision and mission (45%). Conclusions This study is the first comprehensive evaluation of MD/Masters programs in the United States that includes a summary of the medical schools with the largest dual degree programs and their reasons for offering them. The findings support the hypothesis that allopathic medical schools recognize the need for a transdisciplinary approach to prepare students for the complexities in healthcare. These programs provide students with opportunities for additional areas of expertise, leadership development, enhancement of competitiveness for residency application, and interdisciplinary collaboration. Medical schools without dual-degree programs may consider developing these programs to provide benefits to students and institutions.