The intent of this study was to evaluate the program effectiveness of the Project P.A.T.H.S.  (Secondary 1 Curriculum) by analyzing 207 school-based program reports, in which program implementers were invited to write down five conclusions based on an integration of the subjective outcome evaluation data collected from the program participants and program implementers. Secondary data analyses were conducted and 1,855 meaningful units were extracted from 1,035 “aggregated” conclusions. Among them, about 27 and 18% were related to perceptions of the program and implementers, respectively, and most of them were positive in nature. About one-third was related to perceived effectiveness of the program, and most of them referred to enhancement of students' development in societal, familial, interpersonal, and personal aspects. However, difficulties encountered during program implementation (3.34%) and recommendations for improvement (18.11%) were also reported. The present study replicated the findings reported in previous studies and suggests that the Tier 1 Program of the Project P.A.T.H.S. is beneficial to the development of the program participants.


Innovative professional development approaches are needed to address the ongoing lack of women leaders in science, technology, engineering, and math (STEM) careers. Developed from the research on women who persist in engineering and computing professions and essential elements of women’s leadership development, the Leadership Lab for Women in STEM Program was launched in 2014. The Leadership Lab was created as a research-based leadership development program, offering 360-degree feedback, coaching, and practical strategies aimed at increasing the advancement and retention of women in the STEM professions. The goal is to provide women with knowledge, tools and a supportive learning environment to help them navigate, achieve, flourish, and catalyze organizational change in male-dominated and technology-driven organizations. This article describes the importance of creating unique development experiences for women in STEM fields, the genesis of the Leadership Lab, the design and content of the program, and the outcomes for the participants. Carrie Jenkins felt the presentation to senior management went really well. As a program manager for a mid-sized manufacturing company, she oversaw the largest engineering project the company had ever had. Senior management recognized her and her team for effectively completing the project on time and under budget and promoted her to senior project manager shortly thereafter. What the management team did not know was that 1 year earlier, she was actively engaged in an external job search.1, a 44-year-old engineering manager with 20 years of experience. After graduating with undergraduate and graduate degrees in biomedical engineering, she worked as a design engineer for a consumer products company. Outside of work, she was married with three children and struggled to juggle the constant demands of work and family. While she loved her work, her relationship with her manager, Jerry, was a source of constant stress. Jerry had a command-and-control leadership style and preferred to give orders rather than ask for input or engage in dialog. The advice he often gave Carrie was to adopt a more assertive style when presenting to management. He encouraged her to be dominating, such as pounding her fist to emphatically convey important points. Carrie followed his advice and became more authoritative in her style and highly directive with her associates. However, she never felt comfortable, and it wasn’t working well. Her team operated in silos and seemed to wait for her to make all the decisions, which was a constant source of frustration. After years of trying to motivate the team, she concluded that she was not a good fit for the company and began to look elsewhere.The vignette above is a true story about Carrie JenkinsIn the midst of her job search, her organization learned of a professional development program specifically for women in STEM fields and invited Carrie to attend. Through the experience, Carrie discovered that her preferred leadership style, which was collaborative and democratic, could work effectively. She developed a personal vision and discovered that her values and strengths overlapped well with the organization’s culture. She gained the confidence to be authentic in her approach. Great things began to happen. Her team trusted her more, became more unified, and performed at a higher level. Carrie became re-engaged and re-energized in her work and suspended her job search. A promotion to Program Manager came a few months after her graduation from the program. Carrie reflected upon her experience in this way: “The biggest eye-opener was that I needed to be true to myself and that I can be effective as myself, but I will never be effective trying to be someone else”.The Leadership Lab is a professional and leadership development program specifically for women in the science, technology, engineering, and math fields (STEM) just like Carrie Jenkins. In this article, we describe the origin and design of the program and discuss why this type of professional development is needed to advance and retain women in STEM professions. Finally, we highlight initial outcomes of the program.Women’s participation in the United States. labor force has grown exponentially over the past seven decades to the point where women comprised 47% of the workforce and 52% of professional and management occupations in Previous studies have identified obstacles that women must overcome to be successful in the STEM workplace. These barriers and biases have been summarized into the following categories: structural barriers within the educational system; individual and psychological factors; family influences and expectations; and perceptions of the STEM educational and the workplace experiences . Despiteimplicit bias or second-generation bias  understand the complex factors impacting women in male-dominated professions, (b) recognize the value women bring to the STEM workplace, (c) explore factors for leadership effectiveness, and (d) develop strategies and skills to flourish professionally and personally. Individual, relational, organizational, and socio-cultural factors impacting women’s effectiveness and success were explored throughout the program as illustrated in The program design included seven days of experiential learning, scheduled in three modules over three months. The first module focused on the bias, barriers, and opportunities facing women in STEM and the power of a personal vision. The second module addressed skill development in the areas of leadership and emotional intelligence. The third module focused on skills and strategies for leading the way forward. Topics covered during these modules included gender diversity in organizations, implicit bias, resonant leadership, emotional intelligence, self-efficacy, negotiations, leadership presence, and coaching. Participants completed assessments to encourage self-awareness, including a 360-degree report on emotional intelligence. They were paired with an executive coach and met three times over the course of the program. Coaches worked between residencies to help participants explore their passion, values, career aspirations, emotional triggers and developmental focus. Participants also practiced peer coaching in triads which served as a source of ideas, feedback and psychosocial support for team members. Peer coaching triads met three times during the program. On the final day of the program, the manager of each participant was invited to attend a graduation luncheon, where s/he hear a program summary and insights gleaned by the participants.To date, the program has been offered five times, with three cohort groups representing women in STEM generally and two cohorts representing women in manufacturing. Women participants were nominated and supported by their organizations. Participant work experience ranged from 5 to 25 years. The women represented a variety of positions such as Senior Quality Engineer, Engineering Program Manager and Project Manager for the STEM cohort and Global Environment and Sustainability Manager for the manufacturing cohorts.Over 50 women have completed the Leadership Lab in the past three years, and the feedback has been overwhelmingly positive. In participant feedback collected post-program through surveys and interviews, four themes were mentioned most by the participants: (a) job promotions, (b) heightened awareness of unconscious bias and how to mitigate it, (c) stories of personal transformation around self-efficacy and breaking counter-productive thinking and behavior, and (d) benefits received from coaching relationships.Participants have continued to stay connected with their cohort and with the faculty. Each cohort has created a medium to stay connected; several use Facebook groups, one uses a LinkedIn group, and another meets quarterly by video conference. From these connections, we know that the attendees have been retained in their professions, although a long-term study is needed to validate the impact of the program on retention. Based on participant testimonials, it was estimated that about 40% of the women had sought and received a promotion within 12 months of completing the program.Beyond positioning women for advancement, the program helps women to understand and address the barriers often characteristic of male-dominated workplaces and to know ways to better navigate the environment. Take Andrea, for example. She was a research engineer working for an aerospace organization. After 5 years, she felt stuck and did not feel as if she was going to advance. She applied to the Leadership Lab in hopes it would re-energize her and boost her career prospects. While in the program, Andrea applied for a project manager position, which had been a long-time career ambition and was offered the job. Prior to starting, she was contacted by two male managers at another division who invited her to meet. Andrea looked forward to it, thinking it would be good to get to know her new colleagues before working together. The managers had a different idea. Andrea recalled the experience:“Their message was, ‘we don’t think you’re the right person for this job. We think our candidate is better and she should have gotten the job.’ They kept pounding me telling me I shouldn’t have been chosen to be project manager. I sat there stunned at first. Then I stopped them and said, “Hold on. I haven’t even started in the role and you are saying that I’m not a good fit for it? I have a PhD in chemistry and am qualified. Before you say that I cannot do this job, let me do it but don’t complain before I even get started. One of them apologized to me a year later.”Participants report personal transformation especially in terms of deeper self -awareness, social awareness and self-efficacy. In Andrea’s case, she offered:“The program was an eye opener for me because I felt as if a veil was lifted and I finally saw how under-represented women are in my organization. We have 30 project managers and only 1 woman – me. When I give a presentation, they drill me with more questions. At first, I thought it was me, but my co-workers noticed it too. In meetings, men would take the seats at the table and women would sit behind them. I remember thinking this can’t happen anymore, so at the next meeting, I started sitting at the table. The program gave me courage and tools to manage those difficult situations.Before the Leadership Lab, I would not have had the guts to tell the two men what I thought as they criticized me for no reason. I would have listened, and then gone to my supervisor and let him deal with it. But I’m different now. I reflect on the situation and first have the difficult conversations before asking others for help. In the past, I would have waited for someone else to tell me about an open position and now I look for them.”An element of the program that participants highly valued was the executive and peer coaching each one experienced. One participant, Trisha, commented:“For me, this [coaching] was one of the most fulfilling aspects of the course. I learned that I haven’t had much coaching in my career. Receiving feedback from my peers, and a professional coach was awesome! From my peers, I loved having someone listen to me, repeat back what they heard so that I could hear how my words were interpreted, and give me honest feedback. From my coach, I received the greatest gift: someone who helped me articulate my dreams and goals, and bolstered my confidence in being able to achieve them by giving me tools and feedback that helped me realize that what I want is realistic and achievable.”Innovative professional development approaches are needed to address the ongoing lack of women leaders in science and technology-related fields. This article spotlights a new program designed as a research-based professional development immersion for women. The program aim is to equip women with the capability to navigate the complexities in non-traditional professions. While plans are in place to do more thorough long-term studies, early analysis of the program’s outcomes show increases in participant’s self-awareness, self-efficacy, and ability to persist and excel in their chosen profession. These provide encouraging signs of the intervention’s success in advancing and retaining women in STEM and in the manufacturing professions.EVO was the lead author. KB and DB also made significant contributions to this manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


L-Chrebp−/− mice). Hepatic ChREBP deficiency resulted in reduced mRNA levels of glycolytic and lipogenic enzymes, particularly in response to sucrose refeeding following fasting, a dietary regimen that elicits maximal lipogenesis. mRNA and protein levels of SREBP-1c, a master transcriptional regulator of lipogenesis, were also reduced in L-Chrebp−/− livers. Adeno-associated virus-mediated restoration of nuclear SREBP-1c in L-Chrebp−/− mice normalized expression of a subset of lipogenic genes, while not affecting glycolytic genes. Conversely, ChREBP overexpression alone failed to support expression of lipogenic genes in the livers of mice lacking active SREBPs as a result of Scap deficiency. Together, these data show that SREBP-1c and ChREBP are both required for coordinated induction of glycolytic and lipogenic mRNAs. Whereas SREBP-1c mediates insulin’s induction of lipogenic genes, ChREBP mediates glucose’s induction of both glycolytic and lipogenic genes. These overlapping, but distinct, actions ensure that the liver synthesizes FAs only when insulin and carbohydrates are both present.Lipogenesis in liver is highest in the postprandial state; insulin activates SREBP-1c, which transcriptionally activates genes involved in FA synthesis, whereas glucose activates carbohydrate-responsive element-binding protein (ChREBP), which activates both glycolysis and FA synthesis. Whether SREBP-1c and ChREBP act independently of one another is unknown. Here, we characterized mice with liver-specific deletion of ChREBP ( The liver plays a central role in coordinating carbohydrate and lipid metabolism. During fasting, the liver maintains blood glucose by breaking down glycogen (glycogenolysis) and by producing new glucose (gluconeogenesis). Upon feeding, the liver converts ingested glucose into glycogen (glycogenesis) and pyruvate (glycolysis). Glycogen serves as a short-term energy supply in liver and muscle. Pyruvate can enter the mitochondria and be converted into acetyl-CoA, which can enter the Krebs cycle to supply NADH for oxidative phosphorylation, or to produce citrate for FA synthesis. De novo lipogenesis, the pathway of converting acetyl-CoA into FAs, is highly regulated at multiple levels . ActivitInsulin’s stimulation of lipogenic gene expression is mediated by SREBP-1c, a transcription factor that activates all of the genes required for FA synthesis and the first enzyme in triglyceride (TG) synthesis . SREBP-1Srebp-1c or Scap. In these experiments, animals are fasted to provoke hunger and then fed or “refed” a high-carbohydrate/fat-free diet, so that postprandial physiological changes are accentuated  refeeding-induced increases in levels of hepatic lipogenic mRNAs and rates of FA synthesis , the lipogenic response to refeeding was completely abolished   . Althougfew days . The ina induced . Another tissues –31. The Chrebp−/− mice, we have produced and characterized a line of mice with liver-specific ChREBP deficiency (L-Chrebp−/− mice). In marked contrast to the fructose-intolerant Chrebp−/− mice, the L-Chrebp−/− mice consume and tolerate fructose-containing diets, suggesting that hepatic ChREBP deficiency does not contribute to dietary fructose intolerance. The creation of these mice also permitted the study of the interdependent roles of SREBP-1c and ChREBP in regulating the expression of glycolytic and lipogenic mRNAs in liver under basal and carbohydrate-induced states. Combined, our data show that both SREBP-1c and ChREBP are required for the maximal induction of postprandial lipogenesis with fructose feeding. These studies further define the molecular events that contribute to the development of hepatic steatosis associated with excess dietary fructose consumption, which has become epidemic in Westernized societies . Because the presence of the pgkneopA cassette causes inactivation of Chrebp (data not shown), we bred the Chrebp+/fneo mice with a strain of transgenic mice that express a Flp1 recombinase gene under the direction of the human ACTB promoter  to remove the frt-flanked pgkneopA cassette. The resulting Chrebp+/f mice were then intercrossed to produce mice homozygous for the floxed allele without the selection cassette (f/fChrebp ). f/fChrebp  mice were bred to Albumin-Cre transgenic mice  to derive mice homozygous for the floxed Chrebp allele and hemizygous for the Alb-Cre transgene . For brevity, we designate the f/f;Alb-CreChrebp mice as L-Chrebp−/− (liver-specific Chrebp knockout). Littermate f/fChrebp mice were used as controls for all of the experiments. To genotype mice, ear-punch DNA was prepared with a direct lysis kit (Viagen Biotech Inc.) and used for PCR with the primers, 5′-GAAAGGGGTTGGGATCCAAGGGTCC-3′ and 5′-GTGGCTGAGTGGATCATCTGTAAGACTGAT-3′. Ear-punch DNA of wild-type and floxed alleles produced PCR products of 300 and 350 bp, respectively.A conditional targeting vector was produced by the insertion of a cassette  immediatcassette . Three pAll animal experiments described in this work were approved and conducted under the oversight of the University of Texas Southwestern Institutional Animal Care and Use Committee. All mice were housed in colony cages in a room with a 12 h light/12 h dark cycle and were fed a standard chow diet . A high-sucrose diet with 60% (w/w) sucrose, 20% (w/w) casein protein, and 0% fat was purchased from MP Biomedicals (960238). For the fasting and refeeding experiments, mice were divided into three groups: nonfasted (N), fasted (F), and refed (R). The nonfasted group was fed the chow diet ad libitum, the fasted group was fasted for 12 h, and the refed group was fasted for 12 h and then refed with the high-sucrose diet for 12 h prior to study. The starting times for the fasting and refeeding experiments were staggered so that all mice were euthanized at the same time, which was at the end of dark cycle.Animals were euthanized with isoflurane, blood was obtained from the inferior vena cava in EDTA-coated tubes, and plasma was separated and stored at −80°C. Glycogen content of liver was measured with an assay kit from Biovision (K646-100). Plasma glucose, aspartate transaminase, and alanine transaminase concentrations were measured using the Vitros 250 chemistry analyzer . Plasma insulin concentration was measured with an ELISA kit from Crystal Chem, Inc. (90080).10-tagged protein containing amino acids 33-250 of mouse SREBP-1a. B-cells from an anti-SREBP-1 antibody-producing rabbit were then fused with the rabbit hybridoma fusion partner, 240E-1, to obtain hybridoma clone 20B12, as described  and subjected to real-time RT-PCR as previously described . All reause 36B4  or ApoB L-Chrebp−/− livers were used to synthesize first-strand cDNAs using the PrimeScript First Strand cDNA synthesis kit from Clontech (6110A), which were used as templates for PCR amplifications. Two PCR reactions were carried out with PfuUltra II polymerase (Agilent Technologies) using 5′ primers corresponding to the 5′ end of either ChREBP-α (5′-GTGGCCATGGCGCGCGCGCTGGCGGATC-3′) or ChREBP-β (5′-GACGCCATCTGCAGATCGCGTGGAGC-3′). Both reactions used the same 3′ primer, 5′-AGGATTATAATGGTCTCCCCAGGGTGCC-3′, corresponding to the common 3′ end of ChREBP-α and ChREBP-β. The abundance of the PCR product amplified by ChREBP-α primers was >10-fold higher than that of ChREBP-β primers. Both products were cloned into pCR2.1-TOPO vector and sequenced. The results confirmed that the PCR product of ChREBP-α primers in the L-Chrebp−/− livers encoded an aberrant ChREBP-α with an internal deletion of amino acid residues 301-826. Likewise, the PCR product of ChREBP-β primers encoded an aberrant ChREBP-β with the internal deletion of the same region. Because the aberrant ChREBP-β is expressed at an extremely low level in L-Chrebp−/− liver , only the aberrant ChREBP-α (designated as ChREBPΔ) was evaluated for activity.Total RNAs isolated from 2 centrifugation and stored at 5% (v/v) glycerol in phosphate-buffered saline at −80°C. AAVs were administered by tail vein injection and the mice were studied 1–2 weeks after the injection, as indicated in the figure legends.DNA fragments encoding ChREBPΔ or nuclear (n)SREBP-1c (amino acids 1-456) of mouse SREBP-1c were cloned into the pAAV-CAG-shuttle-WPRE vector (Applied Viromics), whose expression is under the control of cytomegalovirus enhancer and the chicken β-actin promoter. A DNA fragment encoding full-length mouse ChREBP-α was cloned into pAAV-TBG vector (Vector Biolabs), whose expression is under the control of the human thyroid hormone-binding globulin (TBG) promoter and microglobin/bikunin enhancer. The expression vectors were then packaged into liver-specific adeno-associated virus (AAV)-DJ  by largefloxed Chrebp allele (f/fChrebp) were generated by inserting one loxP site upstream of exon 9 and another loxP site immediately downstream of exon 15 . Cre-mediated recombination removed exons 9-15, which encode various functional domains of ChREBP, such as the proline-rich domain and the basic helix-loop-helix leucine zipper DNA-binding domain present in both ChREBP-α and ChREBP-β isoforms. To generate liver-specific deletion of ChREBP, f/fChrebp mice were bred to transgenic mice that express Cre recombinase driven from the hepatocyte-specific albumin promoter (Alb-Cre) . For brevity, we designate the liver-specific Chrebp knockout mice, L-Chrebp−/−. For all studies, we bred f/f;Alb-CreChrebp males with f/fChrebp females to obtain control f/fChrebp and L-Chrebp−/− littermates. L-Chrebp−/− mice were born at expected Mendelian ratios and were grossly indistinguishable from control littermates from birth to adulthood.Mice carrying the conditional Alb-Cre)  to generL-Chrebp−/− mice  was not detectable in control or L-Chrebp−/− livers, likely due to instability of the ChREBP-β protein . protein . A proteChrebp−/− mice, although they consume normal amounts of starch-containing chow diet, would not ingest high-sucrose/fructose diets and became moribund within a few days  complex carbohydrates in the form of starch], and then switched to a high-sucrose diet containing 60% (w/w) sucrose. As shown in L-Chrebp−/− , and Chrebp−/−  mice. However, the three groups of mice showed drastically different responses once they were switched to the 60% sucrose diet (high-sucrose diet). Consistent with our previous finding   and L-Chrebp−/−  mice was only slightly less than their daily intakes of chow diet . After 7 days of sucrose feeding, the control and L-Chrebp−/− mice only lost 2% and 5% of their initial body weights, respectively  . As a remoribund . The conectively . The datectively .L-Chrebp−/− mice to tolerate sucrose made it possible to explore the in vivo role of ChREBP in the hepatic response to refeeding of high-sucrose diet after fasting, a condition in which the glycolytic and lipogenic genes are maximally induced  (L-Chrebp−/− mice were fasted for 12 h (F) or fasted for 12 h and then refed for 12 h with a high-sucrose diet (R). Nonfasted (N) groups, which were fed chow diet ad libitum, are included as references. The phenotypic parameters and hepatic mRNA levels of the mice used in this experiment are summarized in supplemental Table S2A (nonfasted groups) and supplemental Table S2B . Plasma insulin concentrations were comparable in nonfasted control and L-Chrebp−/− mice. Fasting and refeeding caused similar degrees of fall and rise of plasma insulin in both groups of mice. Plasma glucose concentrations were slightly lower in L-Chrebp−/− mice. Relative to controls, the L-Chrebp−/− mice had elevated liver glycogen content. Similar accumulations of hepatic glycogen were observed previously in whole-body Chrebp−/− mice (L-Chrebp−/− mice to comparably low levels.The ability of the d state) . For thi−/− mice . FastingL-Chrebp−/− mice. The amount of ChREBP-α protein was reduced by fasting and restored upon refeeding in control mice (L-Chrebp−/− livers (L-Chrebp−/− mice exhibited reduced levels of nSREBP-1 protein in the nonfasted state (L-Chrebp−/− mice (L-Chrebp−/− mice were similar (nonfasted) or slightly higher (fasted or refed) than those of controls under the matched dietary conditions. In both strains, Insig-1 fell during fasting and rose with refeeding, whereas Insig-2 was elevated by fasting and repressed by refeeding, as reported previously , whereas ChREBP-β mRNA was elevated 11-fold. The postprandial inductions of ChREBP-α and ChREBP-β mRNA are consistent with previous studies  in L-Chrebp−/− livers was approximately 40% that of full-length ChREBP-α mRNA in controls. ChREBP-β (full-length or aberrant) mRNA was nearly undetectable in L-Chrebp−/− livers, consistent with the idea that ChREBP-β expression requires functional ChREBP-α  mRNA, on the other hand, was elevated by ∼2-fold in L-Chrebp−/− livers relative to that of controls , similar to that in livers of germline Chrebp−/− mice  . These i−/− mice .L-Chrebp−/− livers was 44% less than that measured in controls and partially explains the reduced SREBP-1 protein levels shown in L-Chrebp−/− mice.The level of SREBP-1c mRNA was increased by 46-fold  in sucrose-refed control mice . The indL-Chrebp−/− mice . These changes paralleled with levels of nSREBP-2 .In contrast, mRNAs encoding cholesterol biosynthetic enzymes, which are predominantly controlled by SREBP-2, i.e., HMG-CoA synthase and HMG-CoA reductase, were induced to comparable levels in sucrose-refed control and nSREBP-2 , confirmL-Chrebp−/− mice were paradoxically higher than those of control mice under all three dietary conditions . The increase of hepatic TG in the face of decreased hepatic lipogenesis was also observed in other studies of fructose-fed mice , the mice were subjected to fasting and refeeding with high-sucrose diet. As shown in L-Chrebp−/− mice was markedly reduced relative to that of refed control mice , which are direct targets of ChREBP, but not of SREBP-1c.L-Chrebp−/− mice -2, SCD-1, and G6PD mRNAs were restored to levels comparable to those of sucrose-refed control mice. The reduced expression of other mRNAs encoding lipogenic genes were either partially restored  or were not restored by AAV-nSREBP-1c . These data indicate that, in the absence of ChREBP, SREBP-1c alone is not sufficient to mediate the full refeeding-induced lipogenic response.Relative to those of controls, mRNAs encoding enzymes for FA synthesis and NADPH production were all reduced by 75% to 95% in the livers of AAV-GFP-injected −/− mice . In the L-Scap−/− mice)  –22. In leviously –22 . The expression of SREBP-1c mRNA and protein as well as lipogenic mRNAs were also restored by AAV-ChREBP-α . These data further support the hypothesis that the postprandial induction of SREBP-1c requires ChREBP, and that both transcription factors are required to coordinate the postprandial lipogenic response.To verify the efficacy of AAV-ChREBP-α, we administered the AAV-ChREBP-α to L-Chrebp−/− mice normalized the sucrose-induced stimulation of a subset of lipogenic genes, while not affecting any glycolytic genes. Conversely, in L-Scap−/− mice lacking all SREBPs, ChREBP failed to normalize the postprandial induction of lipogenic genes. Together with previous studies, these results demonstrate that SREBP-1c and ChREBP are both required for the coordinated induction of glycolytic and lipogenic mRNAs in response to excess carbohydrates. Whereas SREBP-1c mediates insulin’s induction of lipogenic genes, ChREBP mediates glucose’s induction of both glycolytic and lipogenic genes. This provides a potential mechanism to ensure that the liver will not synthesize FAs unless insulin and glucose are both present.The current results demonstrate an essential role for ChREBP in regulating glycolysis and lipogenesis in mouse liver and the interdependence of ChREBP and SREBP-1c for the coordinated maximal induction of lipogenesis by carbohydrates. Hepatic deletion of ChREBP reduced the basal levels of glycolytic and lipogenic mRNAs and prevented the induction of these genes in response to sucrose. Virally mediated restoration of nSREBP-1c in L-Chrebp−/− mice, in marked contrast, can adapt and tolerate sucrose feeding, which is consistent with a previous report . This restoration was likely mediated by direct binding of ChREBP to the ChoRE motifs in the promoter region of Srebp-1c to increase SREBP-1c mRNA and precursor protein   , suggestChrebp−/− mice fed with a high-fructose diet  are also required for normal rates of lipogenesis. LXRs are members of the nuclear receptor family of transcription factors that are activated by oxysterols and cholesterol intermediates , 59. LXRSrebp-1c, Chrebp-α, Chrebp-β, Fas, Abc-g5 (P = 0.06), and Abc-g8, were all reduced in L-Scap−/− mice . Administration of a synthetic LXR agonist, T0901317, to L-Scap−/− mice restored hepatic ABC-G5 and ABC-G8 mRNAs to levels similar to those in control mice, and partially restored SREBP-1c mRNA. The same T0901317 treatment, however, failed to restore the hepatic expression of Chrebp-α or Chrebp-β . This suggests that SREBP activity, independent of producing LXR agonists, supports ChREBP expression, at least under certain dietary conditions. Indeed, T0901317-mediated induction of ChREBP mRNA was also blunted in the livers of Srebp-1c−/− mice (data not shown). Thus, LXR’s regulation of ChREBP is mediated by the direct action of LXR on the Chrebp promoter (Previous studies , 62, 63 promoter  as well promoter , 58, 59.Chrebp and its glycolytic target genes was not different between sucrose-refed control and L-Scap−/− mice. The sucrose-mediated induction of Chrebp and its glycolytic target genes was also comparable between the livers of control and LXR-deficient mice (Srebp-1c and its lipogenic target genes by sucrose-refeeding was abolished in the absence of Scap . One pos et al.  only dels et al. , the cons et al. , 46. Thes et al.  suggestsIn summary, together with previous reports –7, 9, th


Objective The Sedgwick County Healthy Babies Healthy Start (HBHS) program provides community-based services  aimed at reducing racial/ethnic disparities in poor birth outcomes. The purpose of this study is to assess the effectiveness of the Sedgwick County HBHS program by comparing the birth outcomes of program participants who enrolled prenatally and those who did not participate while pregnant. Methods In this retrospective cohort study, we used data drawn from the Sedgwick County HBHS program. The sample included 280 clients who were enrolled in the Sedgwick County HBHS program between September 2014 and December 2015. We performed logistic regression analyses to assess the associations between enrollee type  and birth outcomes . Results The majority of the sample consisted of racial/ethnic minority women . After adjusting for covariates, women who enrolled in the Sedgwick County HBHS program prenatally were less likely than women who were not enrolled during pregnancy to have a preterm birth  and deliver a low birth weight infant . Conclusions for Practice Women, particularly minority women, who participate in the HBHS program experienced better birth outcomes than women who did not participate in the program during pregnancy. However, findings also suggest that interconceptional enrollees may stand to benefit from continued participation in the program. Healthy Start has three distinct program features  which have been shown to improve maternal and infant health outcomes. Our findings reveal that women who participated in the Sedgwick County Healthy Babies Healthy Start program had better birth outcomes than women who did not participate during their pregnancy. These findings have important implications for future initiatives focused on minority women.In the United States, preterm birth (birth at >37 weeks gestation) and low birth weight (weighing >2500 g at birth) are leading causes of infant mortality and morbidity , initiated in 1991, is the largest multilevel, federally-sponsored program to address racial and ethnic disparities in birth outcomes  of Sedgwick County HBHS program participants. Program staff exported participant data from their EHR database into a spreadsheet that included the data records of 433 women who were enrolled during the first phase of the Healthy Start grant year (September 2014–December 2015). Records for participants who were currently pregnant or had not delivered an infant during the 15-month time period were excluded. The resulting analytic sample included 280 clients. Two-hundred and twenty-two clients were ‘prenatal enrollees’ who enrolled in the program while pregnant and participated in the program a minimum of 3 months prior to delivery. Fifty-six clients were ‘interconceptional enrollees’ who enrolled in the program within 3 months after a delivery. During intake, the Sedgwick County HBHS medical providers complete interconceptional enrollment and assessment forms with interconceptional enrollees. The interconceptional enrollment and assessment forms were designed by the Sedgwick County HBHS EHR provider in conjunction with HRSA to ensure the collection of data necessary for HRSA grant reporting requirements.This study was reviewed and approved by the Institutional Review Board at the Kansas Department of Health and Environment.The primary outcome measures were low birth weight (LBW) and preterm birth (PTB). LBW was measured with a dichotomous variable indicating whether birthweight was less than 2500 g . PTB was also measured with a dichotomous variable indicating whether a birth occurred at less than 37 weeks gestation . The predictor variable was a dichotomous variable representing timing of enrollment .Covariates included employment status , insurance status , and chronic health condition . Other demographic characteristics included age , race/ethnicity , primary language spoken , marital status , and highest level of education completed .p < .05 level. Statistical analyses were conducted using SPPS Version 21.Percentages were calculated to summarize the demographic characteristics of women included in the present study. Chi square analyses were conducted to evaluate potential differences between women who were enrolled in the HBHS program prenatally and women who were not . Demographic variables that were statistically significant were included as covariates in the logistic regression models. Two logistic regressions were conducted to assess associations between timing of enrollment , preterm birth and low birth weight. Covariates included in the regression models were employment status, insurance status and chronic health condition. All statistical tests were two-tailed with significance accepted at the As shown in Table As shown in Table Table t(7) = 1.13, p = .99.Logistic regression results indicated that after adjusting for employment status and chronic health conditions, women who were enrolled in the HBHS program prenatally were five times less likely than women who were not enrolled in the HBHS program during pregnancy to deliver preterm . The regression model demonstrated high predictive accuracy (88.6%) and good fit, t(6) = 2.71, p = .84.After adjusting for employment status and chronic health conditions, women who were enrolled in the HBHS program prenatally were also three times less likely than women who were not enrolled in the program during pregnancy to deliver a low birthweight infant . The regression model demonstrated high predictive accuracy (94.1%) and good fit, The findings from this study suggest that the provision of maternal care coordination and home visitation in an integrated model during pregnancy may favorably impact women’s birth outcomes. The majority of the women participating in the Sedgwick County HBHS program were non-Hispanic black and Hispanic. Considering that babies being born preterm/LBW account for 33.1% of infant deaths among non-Hispanic blacks and 23.3% of infant deaths among Hispanics(Kansas Department of Health and Environment Several limitations should be considered in interpreting the study findings. First, there are limitations regarding the comparison of the two groups. In the interest of understanding differences in outcomes based on timing of enrollment, we compared the birth outcomes of prenatal enrollees and interconceptional enrollees. However, birth outcomes for interconceptional enrollees were based on retrospective self-reported information gathered by a medical provider during program intake. In many cases, the Sedgwick County HBHS program is not able to obtain all records for interconceptional enrollees. In contrast, outcomes for prenatal enrollees were gathered from records obtained while the client was enrolled in the Sedgwick County HBHS program. It is possible that interconceptional women, who enrolled in Sedgwick County HBHS after a recent birth, may have been subject to recall bias. Second, prenatal enrollees were overrepresented in the study sample which could have influenced the findings. Third, the small sample size limits our ability to generalize findings to a larger population of Healthy Start participants. Finally, HBHS provides a set of multifaceted interventions, and it was not possible to tease apart which specific intervention contributed to the study’s findings. Although we did not focus on process, we attempted to provide some insight into program delivery characteristics using available data.Despite study limitations, our findings contribute to the empirical literature on the benefits of enrollment in HBHS programs using an integrated model on birth outcomes among racially and ethnically diverse clients. High-risk racial/ethnic minority women, in particular, stand to benefit from this program. This has specific implications for Sedgwick County, KS which is challenged by high preterm birth rates. The present study also offers important insights into the interconception client population who may enter into the program with more health risks and less support. It is important to recognize that interconceptional clients may stand to benefit from long-term participation in the HBHS program. For example, by providing interconception care services to women in a non-Medicaid expansion state, HBHS is able to fill important gaps in access. Future longitudinal studies are needed that follow women over time to study temporality between HBHS participation and birth outcomes. Future studies should also consider employing rigorous methods to assess HBHS program dosage and intended program outcomes. Moreover, future studies should not only consider examining the effects of each program component on clients’ health and birth outcomes, but also how they may differentially impact outcomes among program participants. Future program design can be enhanced by research identifying the most important aspects of the integrated model that contribute to favorable outcomes.


Mhttp://quake.geo.berkeley.edu/cnss/, an official website of the Northern California Earthquake Data Centre, USA. Each datum comprised the earthquake occurrence date, time of the earthquake occurrence, epicenter’s coordinates, focal depth and magnitude. The Gutenberg-Richter’s relationship being the longest observed empirical relationship in seismology, analysis of variance and time series were used to analyze the seismicity of the study area. Annual distributions of earthquake occurrence based on magnitude variations with the limit 0 MF-value for the period of 1966–1975, 1976–1985, 1986–1995, 1996–2005, 2006–2015, and the entire period of investigation ranging from 1966 to 2015 were determined so as to investigate the variations of these parameters on earthquake occurrence over time. The histograms of earthquake occurrence against magnitude of earthquakes for the selected years , and the decadal frequency distributions of earthquake occurrence were also plotted. The focal depth occurrence for each magnitude bins  were grouped into shallow, intermediate, and deep depths ranging from 0 to 70, 71 to 300, and 301 to 700 km as being used in seismology. The neural network analysis was also applied to the magnitude of the earthquake. The network uses a time series magnitude data as input with the output being the magnitude of the following day. If the nature of the earthquakes time series is stochastic, modeling and prediction is possible. The earthquake data sets presented in this article can further be adopted in the study of seismicity pattern, b-value using series of models, earthquake prediction and variations of earthquake parameters on African and/or Arabian plates. When this approach is integrated with other technique(s), it can provide insights to stability of African lithospehric plates especially the coastal region of Africa.This article evaluates the occurrence of 0  Specifications TableValue of the data•Can be used to study the seismicity pattern in African and/or Western Asia region.•b-value estimation using integrated models in African – Western Asia seismology.Can be used for •Can be used to study the effect of earthquake occurrence on African and/or Arabian lithospheric plates.•Can be used to estimate the time scale dependence of earthquake parameters in subregions of Africa   and Midd•Can be used to forecast the earthquake occurrence in African and/or Western Asia region.•Can be integrated with other computational approach for earthquake interpretation.•Can be used to further explain the stability of African lithospheric plates.•For educational purposes on seismically active zones in African – Asian region.•Can be correlated with other earthquake data for seismic activity studies in coastal region of Africa and Middle East.•Can be employed in the study of seismic activities around the equator when integrated with other techniques such as aeromagnetic data and geographic information system approach.•It can provide insights to further exploration of aseismic zones being affected by tremors in Africa especially Nigeria.1MThe data in this article contains the record of earthquake occurrence in African – Western Asia region. The seismic events were recorded by the seismographs of the Northern California Earthquake Data Centre, USA. The data were obtained for the 0 to 60° E , focal db-value which varied from 0.2 to 2.0, and generally found around 1. This is the measure of stress on the lithospheric plates, because lower b-values indicate that the stress is optimum in the investigated region. Generally, very low b-values are found in case of immediate aftershocks and higher values are found in case of swarm. There are two mostly used methods in estimation of b-values: least square and maximum likelihood methods Ma-values) and tectonic character  for the period of 50 years (1966–2015). Globally, GR equation has been applied to earthquake data for the estimation of b-values and related parameters, but few reports from African continent are available in the literature An earthquake is caused by a sudden slip along a fault zone. It has been recognized as one of the most destructive of all natural hazards which can severely destroy the entire vicinity in seconds without an explicit warning N is the cumulative number of earthquakes of magnitude ≥ M, a characterizes the seismicity level of a region, which represents the M > 0 earthquake. b defines the tectonic character, which is a function of the accumulated stress of a region. In addition, a and b are constants that vary in space and time.The GR law has remained one of the oldest empirical relationships that are still relevant in seismology till date. The relationship is based on power scaling relationship, which relates the frequency and the magnitude of earthquake together in order to predict the degree of stress on the lithospheric plate in a region. The GR equation The descriptive analysis has also been found useful in the evaluation of earthquake occurrence in a region. This ranged from description of earthquake occurrence by plotting the graphs of frequencies of earthquakes against their coordinates Furthermore, in earthquake predictions, several phenomena have been considered by researchers. The considered parameters are electromagnetic fields, seismicity pattern, unusual cloud and weather parameters, unusual emanation of hydrogen and radon gases from the subsurface (e.g. groundwater or soil), animal behaviours The neural network developed in this article uses only time series magnitude data as input with the output being the magnitude of the following day. Time series is defined as a sequence of values documented in chronological order over time. Occurrence of previous events may be extremely valuable in prediction of its behaviours in the future. As reported by 2African-Arabian or Western Asia region constitutes all the countries presented in Generally, Arabian and African continent are made up of a PreCambrian basement of crystalline meta-sedimentary, igneous and meta-igneous rocks . This cr3The magnitude of an earthquake is determined based on the information received by the seismograph. The Richter magnitude involves measuring the amplitude of the largest recorded wave at a specific distance from the seismic source. The magnitude of earthquake and its implications are presented in M ≤ 0.9 earthquakes showed total events of 154, 1 ≤ M ≤ 1.9 earthquakes showed total events of 2347, 2 ≤ M ≤ 2.9 earthquakes showed total events of 17640, 3 ≤ M ≤ 3.9 earthquakes showed total events of 33010, 4 ≤ M ≤ 4.9 earthquakes showed total events of 20922, 5 ≤ M ≤ 5.9 earthquakes showed total events of 3388, 6 ≤ M ≤ 6.9 earthquakes showed total events of 216, 7 ≤ M ≤ 7.9 earthquakes showed total events of 18, and 8 ≤ M ≤ 8.9 earthquakes being the least recorded event occurred once in 1969. M ≤ 5.9. Seismic events were recorded yearly within this range, which varied from as low as 2 events in 2012 for 3 ≤ M ≤ 3.9 to very high events of 3314 in 2008 for the same range of magnitude.The annual distributions of seismic activities based on the magnitude of earthquakes are presented in M ≤ 3.9 earthquakes were most frequent, with the total events of 33010. In M ≤ 4.9, with the total events of 2199 and 3302 respectively. However, M ≤ 3.9, with the total events of 8062, 13392, and 9496 respectively. The decadal frequency distribution of earthquake occurrence plotted in The data sets were further explored by constructing the histograms of frequency of earthquake occurrence against the magnitude for the period of 50 years (1966–2015) a, and 10The focal depths of the earthquake data sets were also analyzed. The focus of an earthquake is the actual point where the rocks break in the subsurface. The depths of the focus are categorized as shallow (0–70 km), intermediate (71–300 km), and deep depth (301–700 km below the earth surface) respectively b-value. However, the a-value (seismicity level) was estimated by substituting the known parameters into the GR equation. The magnitude of completeness (MC) of the earthquake catalogue was also determined for each period. The MC is referred to as the threshold magnitude which is the magnitude above which all earthquakes were recorded.The frequency-magnitude distributions of earthquake occurrences for the period of 50 years (1966–2015) and 10-year interval covering the entire investigated period were produced through the GR relation Eq. . This waa-value, b-value, MC value and Adjusted R-square (Adj. R-square) value of each analysis being displayed on each graph. The Adj. R-square is a corrected goodness of fit (model accuracy). It is calculated by dividing the residual mean square of error by the total mean square error. The complete data sets during the period of 1966–2015 revealed that the b-value of the study area is 0.61, a-value is 6.01, MC is 1.85, and Adj. R-square is 0.84 respectively. The analysis across the five (5) decades showed that the b-value fluctuates from 0.45 (during the first decade) to 0.65 (during the fourth decade), a-value from 4.40 (during the first decade) to 5.60 (during the fourth decade). The MC varied from 1.80 to 2.00.The GR plots for the period of 1966–2015, 1966–1975, 1976–1985, 1986–1995, 1996–2005, 2006–2015 were presented as F-tests to statistically analyze or test the equality of means. The test was named after Sir Ronald Fisher. The F-test is the ratio of two variances (measure of dispersion), being the square of standard deviation. The ANOVA results of the data sets covering the period of 1966–2015, and five decades  are presented in F-values recorded for the periods of 1966–2015  is 430.73, 1966–1975 is 267.62, 1976–1985 is 322.91, 1986–1995 is 527.75, 1996–2005 is 535.97, and 2006–2015 is 405.09 respectively.Statistical analysis involving the Analysis of Variance (ANOVA) was carried out on the magnitude of the earthquakes. This analysis is used to determine the difference in the mean of sets of data or groups. The ANOVA uses y(t) and past values from a second time series x(t) using a nonlinear autoregressive with exogenous input (NARX). The second task is to only predict future values from the past values of such time series using a nonlinear autoregressive (NAR) input. The third task is to predict future values from the previous values without having knowledge of previous values using input–output model instead of NARX. The magnitudes of the earthquake were imported, validated and tested such that 70% of the data were used for the training while 15% each will be used for validation and testing of the dataset. The graphical interfaces of the treated data were presented from The earthquake forecasting approach from historic seismic data is prevalent nowadays The qualitative and quantitative approach employed in this article can be beneficial in the study of stability of the African lithospheric plates. The data sets can be reexamined to estimate the time scale dependence of earthquake parameters in subregions of Africa and/or Middle East. The approach presented in this article can provide insights to researchers on further explorations of aseismic zones being affected by tremors in Africa such as Nigeria


ARID1A) was frequently mutated in cancers. The modulation mechanism of ARID1A for PI3K/AKT signaling in gastric cancer (GC) remains elusive. Here, we found that depletion of endogenous ARID1A enhanced the in vitro proliferation, colony formation, cellular growth, nutrient uptake and in vivo xenograft tumor growth of GC cells. PI3K/AKT activation by ARID1A-silencing was profiled using a phospho-protein antibody array. The phosphorylation of PDK1, AKT, GSK3β and 70S6K, and the protein and mRNA expressions of PI3K and PDK1, were upregulated by ARID1A-silencing. Chromatin immunoprecipitation and luciferase reporter assay revealed that ARID1A-involved SWI/SNF complex inhibited PIK3CA and PDK1 transcription by direct binding to their promoters. Serial deletion mutation analyses revealed that the ARID1A central region containing the HIC1-binding domain, but not the ARID DNA-binding domain and the C-terminal domain, was essential for the inhibition of GC cell growth, PI3K/AKT pathway phosphorylation and its transcriptional modulation activity of PIK3CA and PDK1. The proliferation, cellular growth and glucose consumption of ARID1A-deficient GC cells were efficiently prohibited by allosteric inhibitors mk2206 and LY294002, which targeting AKT and PI3K, respectively. Both inhibitors also downregulated the phosphorylation of PI3K/AKT pathway in ARID1A-deficient GC cells. Such cells were sensitized to the treatment of LY294002, and AT7867, another inhibitor of AKT and p70S6K. The administration of LY294002 alone inhibited the in vivo growth of ARID1A- deficient GC cells in mouse xenograft model. Our study provides a novel insight into the modulatory function and mechanism of ARID1A in PI3K/AKT signaling in GC.The tumor suppressor gene AT-rich interactive domain-containing protein 1A ( Recently, a novel tumor suppressor AT-rich interactive domain-containing protein 1A (ARID1A) has been found to be frequently mutated in human cancers, including 8–27% of GCs [ARID1A encodes BRG1-associated factor 250 a (BAF250a), a noncatalytic subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin-remodeling complex [Gastric cancer (GC) is the fourth and sixth most common cancer in men and women, respectively. The estimated incidence of GC is around 952,000 cases worldwide, along with 723,000 deaths, according to GLOCOCAN statistics in 2012  and SMAD3 transcription and tumor growth in gynecologic cancers [E2F1 [CCNE1 [c-MYC [ARID1A silencing increased the migration and invasion abilities of liver cancer cells [oft agar . Silencie effect , 21. ARI cancers . ARID1A rs [E2F1 , CCNE1 [1 [CCNE1  and c-MY1 [c-MYC , 28. ARIer cells . We founer cells .ARID1A mutation in cancer tended to occur in a synergistic fashion with PIK3CA [ARID1A in glioma, ovarian and colon cancer cells upregulated the phosphorylation of AKT and P70S6K [h PIK3CA , 29–32. d P70S6K –35. Despin vitro and in vivo. We performed a phosphorylation profiling of PI3K/AKT signaling in GC cells with ARID1A depletion and identified the direct transcriptional targets of ARID1A in PI3K/AKT pathway. We also mapped the essential region of ARID1A protein in the transcriptional regulation of its target genes. We analyzed the in vitro and in vivo drug responses of GC cells with ARID1A depletion.In the present study, we analyzed the ARID1A functions in GC cell proliferation, cellular growth and nutrient consumption ARID1A in GC cell lines MGC-803, AGS, HGC-27 and/or SGC-7901 using a siRNA or shRNAs. The siRNA remained as effective till 5 days post-transfection  and heavier (p = 0.04) tumors than the controls with luciferase silencing  of dy array . The phody array . These rt Figure . InteresARID1A increased p-AKTS473 in Hela cells  and SMAD3, were decreased in HGC-27 with ARID1A silencing  significantly downregulated the proliferation of 293FT cells  (aa 1017–1108), a HIC1-binding domain (aa 1355–1424)/Gln domain (aa 1327–1404) , a glucon Figure . Overexps Figure  and the s Figure . PTEN haS Figure  and 4E aS Figure , suggesty Figure . Overexp Figures . We failARID1A deficiency. Given that PIK3CA mutation occurs frequently in a synergistic fashion with ARID1A, we focused on the drug effectiveness of small inhibitors against PIK3CA, as well as p-AKT, which is a “hub” target of diverse tumorigenic signaling. Although the drug sensitivity of ARID1A-deficiency has been analyzed in ovarian cancer cell lines [in vivo effectiveness of PI3K/AKT inhibitors for GC cells with ARID1A depletion has been addressed.The above findings suggested that PI3K, PDK1 or p-AKT might be the therapeutic targets of GCs with ll lines , no in vARID1A was silenced in HGC-27 and SGC-7901 cells, which were treated with mk2206, an allosteric inhibitor that inhibits Akt phosphorylation. p-AKTS473 and cell growth were obviously upregulated by ARID1A depletion but were suppressed by mk2206 treatment   than in ARID1A-intact cells (1.615)   than the control cells with native ARID1A (LogIC50 = 1.772)   and HGC-27  to AT7867, an inhibitor against AKT and p70S6K  Figure . In HGC-) Figure . ARID1A K Figure  and 6D.ARID1A-depletion were significantly shrunk by LY294002 treatment comparing with mock controls after 8 days of administration (p = 0.041 at 8th day and p = 0.043 at 9th day)  Figure . HoweverARID1A-deficiency.These observations suggested that mk2206 and LY294002 targeting PI3K/AKT signaling could effectively suppress the proliferation of GC cells with ARID1A gene emerges as a bona fide tumor suppressor, while its function and molecular mechanism in GC remains elusive. Although ARID1A has been observed to regulate GC cell proliferation by in vitro experiments [in vivo evidence was established to date. Here we verified the tumorigenesis role of ARID1A knockdown in GC by in vivo xenograft mouse model and in vitro proliferation analyses. Another interesting finding was that ARID1A depletion enhanced cellular nutrient uptake and increased average cell size, suggesting ARID1A deficiency enhanced tumorous metabolism processes other than accelerating cell cycle, suppressing apoptosis, triggering EMT and increasing cancer cell migration/invasion [eriments , 21, no invasion , 27, 40.ARID1A depletion using an antibody array and Western blot. The increased phosphorylations of AKT, PDK1, TSC2, mTORC1 and p70S6K were in line with the enhanced cellular growth of GC cells. The increased phosphorylation of GSK3β was in agreement with the upregulation of glucose consumption, while the phosphorylation of p27 Kip1 and p21 Cip1, two cell cycle inhibitors, were related with accelerated cell cycle. The upregulated phosphorylation of BCL2 were associated with an inhibition of apoptosis [S166 indicated a suppression of p53 function [S134/S136 and 14-3-3 contributed to GC cell survival. These results suggested that the activation of PI3K/AKT pathway by ARID1A depletion contributed to multiple cellular alterations including uncontrolled cell cycle, increased survival ability and enhanced nutrient uptake, which had been addressed with additional experiments in current study.In current study, we profiled and verified the phosphorylation of PI3K/AKT pathway in GC cells with poptosis . Increasfunction . The incARID1A deficiency has been observed, no direct link was established between ARID1A, a transcriptional regulator, and PI3K/AKT pathway, a typical pathway by phosphorylation cascade [PIK3CA and PDK1 were the direct transcriptional targets of the ARID1A-involved SWI/SNF complex. Furthermore, we found that the negative regulation function of ARID1A for PIK3CA and PDK1 was independent of its N-terminus containing the ARID domain, the LXXLL motifs and its C-terminal fragment containing the GR-binding domain, but interestingly relied on the central region containing the HIC1-interaction domain. ARID domain was known to mediate the binding of ARID1A to DNA sequence in a non-specific fashion [et al identified that GR-dependent transcriptional activation was reduced slightly by the deletion of the ARID DNA-binding domain but was dramatically reduced by the deletion of its C-terminal GR-binding domain (aa 1637 to 2285) [et al reported that the C-terminus (aa 1759 to 2285) of ARID1A, the same fragment as ARID1A-C3 in our study, interacted with p53 to regulate the transcription of p21, a downstream target gene of p53 [et al [E2F1 transcription through the recruitment of SWI/SNF complex by a direct interaction with ARID1A [ARID1A is one of the 9 to 12 subunits of SWI/SNF chromatin remodeling complexes which contributed to nucleosome remodeling and transcriptional regulation of a broad profile of target genes , 36. Alt cascade , 39, 43. fashion . Nie Z eain aa 16 to 2285 e of p53 . Althoug3 [et al , however3 [et al , which ih ARID1A . ARID1A/ARID1A-deficiency showed some in vitro sensitivities to PI3K/AKT inhibitors [in vivo responsiveness of GC cells with ARID1A-deficiency effectiveness of PI3K/AKT inhibitors has been addressed. We analyzed the effects of chemical inhibitors against PI3K/AKT signaling in vitro and in vivo. Mk2206 and LY294002, which respectively targeting p-AKTS473 and PI3K, were effective to downregulate GC cell proliferation, glucose consumption and cellular growth (cell size) conferred by ARID1A depletion. Accordingly, the PI3K/AKT signaling was downregulated by mk2206 or LY294002. The drug sensitivity of ARID1A-deficient GC cells was increased for the treatment of LY294002 and AT7867, another inhibitor against AKT and p70S6K. The administration of LY294002 alone inhibited the in vivo growth of the xenograft tumors with ARID1A silencing, comparing with the cells with native ARID1A.As described above, the transcriptional mechanism of ARID1A would be addressed to deal with the heterogeneity of different cancers and physiological and pathological variations. Although ovarian cancer cell lines with hibitors , no in vARID1A confers an increased proliferation, cellular growth and nutrient consumption of GC cells, companied with an activation of PI3K/AKT signaling. PIK3CA and PDK1 were the direct transcriptional targets of the ARID1A-involved SWI/SNF complex. The central region containing the HIC1-binding domain of ARID1A was essential for its transcriptional regulation of downstream targets. ARID1A deficiency and the activation of PI3K/AKT were hazard factors of GC patients and associated with poor prognosis. MK2206 and LY294002 were effective to suppress the proliferation of GC cells with ARID1A deficiency by downregulating activated PI3K/AKT signaling. Our study provides a novel insight into the function and mechanism of ARID1A in the modulation of PI3K/AKT signaling in GC.Taken together, our study revealed that deficient 2. Hela and HEK293FT were cultured in DMEM supplemented with 10% FBS. The cell lines were authenticated on August, 2014.GC cell lines HGC-27 and MGC-803 were purchased from the Cell Bank of Shanghai Institutes for Biological Sciences, China. SGC-7901 was generously provided by Dr. Jian-Jun Du at Huashan Hospital, Fudan University. AGS was a gift by Dr. Qing-Hua Zhang at the Shanghai University of Traditional Chinese Medicine. GC cells were cultured in RPM1640 media supplemented with 10% FBS in a humidified incubator at 37°C and 5% COARID1A gene was cloned as described previously [The eviously . The shReviously . Lentivieviously . The priImmunoblotting analysis was performed as previously described . All antARID1A silencing according to the procedure established previously [Immunofluorescence was performed to monitor the proliferation of GC cells after eviously .ARID1A) using the Extraction Buffer . Next, 25 μg proteins of each sample were labeled with 30 μg biotin in 4% N,N-Dimethylformamide solution. The reaction was stopped after 2 hours of incubation at room temperature. The labeled proteins were diluted with 6 mL Coupling Solution . The antibody arrays were blocked with the Blocking Reagent  at room temperature for 45 min and then rinsed 10 times with Milli-Q water. The diluted labeling products were incubated with the antibody arrays at 4°C overnight. The array slides were washed with Milli-Q water as above. The conjugated proteins on the array slides were detected with Cy3-streptavidin (0.5 μg/mL) solution. The slides were scanned using a microarray scanner GenePix 4000B with software GenePix Pro 6.0 . The raw data was treated with the Grubbs' algorism and outliers in each six-repeat data point of an antibody were excluded. The data was average for each antibody and all data were normalized using the average against beta-actin. The phosphorylation ratio = phospho/unphospho. The phosphorylation fold change = (phosphorylation sh2-ARID1A)/(phosphorylation sh-Luciferase). The proteins with a fold change ≥ 1.8 were reported in t test and a p value < 0.05 was considered as statistically significant.The experiment was performed by Wayen Biotechnologies (Shanghai), Inc., using the Full Moon AKT/PKB phospho antibody array containing 216 antibodies against the corresponding proteins of AKT/PKB pathway . There are 93 paired antibodies, which react with a phosphorylated site and a paired non-phosphorylated site. Proteins were extracted from SGC-7901 or HGC-27 cells stably transfected with sh-Luciferase or sh2  with a Beckman Flow Cytometer . Cells in suspension were fixed by adding 2.5 mL 70% alcohol and incubated at 4°C overnight. Alcohol was aspirated with centrifugation and the cells were washed with PBS/1% BSA triple times and suspended with 50 μg/mL propidium iodide and 0.1 mg/mL RNase. After incubation at 37°C for 40 min, the cells were washed by adding 3 mL PBS/1% BSA. Finally, the cells were re-suspended with 1 mL PBS and analyzed by a cytometer.Cell cycle alteration by Total RNA isolation and qPCR were performed as previously described . PrimersColony formation assay was performed as describe previously .ARID1A siRNAs were synthesized as previously reported [Plasmid or siRNA transfection using lipofectamine (Life Technologies - Invitrogen) and OPTI-MEM reduced serum media (Life Technologies - Invitrogen) was performed as described previously . The celreported . The siRCell proliferation was analyzed using a BrdU Cell Proliferation ELISA Kit  as previously described .6). First, 1 mL of culture medium of each sample was added into a test tube and a standard sample in another tube was prepared by adding 950 μL of water and 50 μL of the Glucose Standard solution into the tube. The reactions were started at zero time by adding 2 mL of the Assay Reagent to each tube at an interval of 30–60 seconds. The tubes were incubated at 37°C for 30 min. The reactions were stopped by adding 2 mL of 12 N H2SO4 into each tube at 30–60 seconds intervals. The absorbance of each tube against the reagent blank at 540 nm was measured using a microplate spectrophotometer. The glucose concentration was calculated as: mg glucose = (ΔA540 of Test) (mg glucose in Standard)/ΔA540 of Standard. The glucose consumption was:  – (glucose concentration at test).Cells were seeded in culture dishes and the media were changed after 6 h. The cells were further incubated for 24 h, and the culture media were collected and used for glucose measurement using a Glucose Assay kit . The assay was performed according to the manufacturer's instructions. The glucose consumption and lactate production were normalized by cell counts (per 10Cell proliferation was measured using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay as previously described . AlternaPIK3CA and PDK1 was amplified using normal human genomic DNA, and inserted into pGL3 luciferase reporter vector  [PIK3CA were cloned, including −1889 to +1 , −1276 to +1 and −516 to +1. The promoter region from −1325 to +1  of PDK1 was cloned for analysis. The primers were deposited in The promoter regions of , China) . Three pChIP assay was performed using an antibody against BRG1 or IgG as a negative control with an EZ-ChIP kit (Upstate Biotechnology) according to the manufacturer's instruction and previous reports , 48. The4 per well) were seeded on a 96-well plate and treated with different concentrations of drug chemicals for 72 hrs at 37°C. The concentrations of LY294002 and AT7867  were 0, 0.01, 0.1, 1, 10 and 100 μM. Twenty μL of MTT solution (5 mg/mL)  was added to each well and the cells were incubated for 4 hrs at 37°C. Finally, 150 μL DMSO was added and allowed to dissolve for 10 min. The absorbance was monitored at 490 nm using a microplate spectrophotometer.Gastric cancer cells (1–2 × 106) mixed with equal volume of Matrigel  were injected subcutaneously into both flanks of each mouse. When the tumor volume reached 100 mm3, the mice were injected intraperitoneally of LY294002  every day with a dosage of 30 mg/kg (body weight). The control group was injected with 1 × PBS (pH 7.4). Tumor diameters were measured using a caliper every two days and the tumor volume was calculated using the formula: V (mm3) = (width)2 × length/2. The mice were executed 30 days after cell inoculation. The tumors were isolated from the bodies and weighed, followed by fixation with 4% neutral paraformaldehyde. All experimental procedures were conducted according to the guidelines of the Animal Experimental Ethics Committee of Shanghai Medical College of Fudan University.The BK nude mice  were 4–5 weeks old at the beginning of the study. These mice were purchased from Shanghai Laboratory Animal Center, Shanghai, China, and allowed to acclimate for 5 days in the animal facility before further intervention. Cells (5 × 10t test. Drug sensitivity statistics was performed using GraphPad Prism 6 and the concentration was Log transformed and the divergence of LogIC50 was evaluated with an F-test. A p value < 0.05 was considered as statistically significant. All statistical tests were two-sided.Differential significance was calculated using unpaired Student's


To observe the choices of conventional disease modifying antirheumatic drugs (cDMARDs) and biologic DMARDs (bDMARDs) in the management of rheumatoid arthritis (RA) in Australian routine clinical practice, to assess treatment survival and determine the effect of cDMARDs/bDMARDs on disease activity. Routinely collected, deidentified clinical data was sourced from 20 Australian rheumatology practices. RA patients aged ≥18 years, who had received cDMARDs/bDMARDs and a recorded subsequent visit, were included. A linear mixed model was used to determine the change over time and the percentage reduction in disease activity was summarized. 12,526 RA patients were included: 72% females, mean age 62 years. cDMARDs and bDMARDs were used in 92% and 30% of patients, respectively. The most commonly prescribed cDMARD was methotrexate (76% patients); median time to stopping treatment was 337 months [95% CI: 279–ND]. Etanercept was the most commonly prescribed bDMARD (12% patients); median time to stopping treatment was 79 months [95% CI: 57–93]. Of 5,341 patients with a first change in medication (cDMARD or bDMARD), 87% had therapy escalation and 13% deescalation. Reduction in DAS28-ESR, 6-month post-DMARDs initiation ranged from 3%, adalimumab, to 14%, leflunomide and tocilizumab. In this large Australian cohort of unselected community RA patients, the choices of cDMARDs/bDMARDs are aligned with current international guidelines. High-quality clinical research underpins our knowledge of the efficacy of various rheumatoid arthritis (RA) therapies –4. RandoRCTs are conducted on carefully selected groups of patients under strict clinical conditions; therefore, it is unclear how the efficacy and safety signals observed in the RCTs will translate into the uncontrolled, relatively unselected environment of routine clinical practice.There are limited routine clinical practice data available that assess the uptake of new treatments in RA patients , 6. SuchThe OPAL-QUMI  consortium  is a poiCEDAR is a multicentre, longitudinal, observational study. The primary objective of the study was to identify the choices of cDMARDs/bDMARDs being made over time for the management of RA in Australian patients. The secondary objectives were to assess the survival of RA patients on treatment and the effects of cDMARDs/bDMARDs on disease activity.The study which was approved by the University of New South Wales Human Research Ethics Committee (reference number HC12094) was conducted in accordance with local guidelines, as set out in the National Statement on Ethical Conduct in Human Research.Patients diagnosed with RA, aged ≥ 18 years, who had received any medication, including cDMARDs, bDMARDs, corticosteroids, or NSAIDs, either as monotherapy or in addition to their stable previous therapy, and who also had subsequent follow-up visits as well as a change in cDMARDs/bDMARDs recorded were eligible to be included in the study. Patients who requested their data not to be collected for research purposes were excluded from the analyses.The study was conducted by the OPAL-QUMI using the clinical software program Audit4 (described previously) . DeidentParameters collected included demographics (gender and age), diagnosis , disease measures (including DAS28-ESR), tender joint count (TJC), swollen joint count (SJC), and laboratory observations  and medications .However, being point of care clinical data, there are parameters missing for some analyses  in these cases; we have highlighted/defined the number of patients included.Medication change was analyzed in 9 prespecified categories: methotrexate monotherapy, combination of >1 cDMARDs, combination of methotrexate and leflunomide, monotherapy of cDMARDs other than methotrexate, monotherapy of bDMARDs, combination of bDMARDs plus methotrexate, combination of bDMARDs plus cDMARDs other than methotrexate, combination of bDMARDs and >1 cDMARDs, and no cDMARDs/bDMARDs therapy. Treatment escalation was defined as a new cDMARDs/bDMARDs being introduced and treatment deescalation was defined as the cessation of cDMARDs/bDMARDs.Treatment survival was defined as the number of months from the first prescription of the drug until the last known date taking the drug. Survival on treatment was analyzed for the most frequently recorded cDMARDs  and bDMARDs . The number of patients on other biologics was too small for any meaningful analyses to be carried out. Government subsidized bDMARDs sequentially became available in Australia for etanercept in 2003, adalimumab in 2004, abatacept in 2008, and tocilizumab in 2010. Hence, data for tocilizumab, in particular, was over a shorter timeframe in this study. The EULAR response criteria were defined according to van Gestel et al., 1996  were provided for continuous variables and frequency counts for categorical variables. The median and distribution of treatment survival were estimated using Kaplan-Meier methodology. A linear mixed model was used to determine change over time and all medications with adequate sample size were included. The assumptions of the linear mixed model were that the observations are normally distributed with a constant variance and independence. The assumptions were assessed graphically.A total of 12,526 RA patients were screened: 72% females, mean age 62 years (range 18–100 years). Demographics and disease characteristics for the bDMARDs and bDMARDs groups are presented in n = 11,511) of patients had at least one cDMARD, 30%  had at least one bDMARD, 58%  had an oral corticosteroid, and 30%  had at least one NSAID (mainly meloxicam and celecoxib). The most commonly prescribed cDMARDs and bDMARDs were methotrexate  and etanercept , respectively, with all prescribed cDMARDs and bDMARDs presented in Ninety-two percent  had their treatment escalated and 681 (13%) had their treatment deescalated. The most common first therapeutic RA medication changes were treatment escalations from monotherapy methotrexate, monotherapy cDMARDs other than methotrexate, and monotherapy bDMARDs .Two thousand one hundred and eighty-four patients had a second change in their medication; 1,244 (57%) had their treatment escalated and 940 (43%) had their treatment deescalated. The most common treatment changes in RA medications at a second change are shown in Over a 6-month period, the change in disease activity was assessed following the commencement of a DMARD. Statistically significant, although clinically modest, reductions in mean DAS28-ESR were observed for methotrexate (9.4%), hydroxychloroquine (9.6%), leflunomide (13.8%), sulfasalazine (12.9%), etanercept (8.9%), and tocilizumab (13.9%). A reduction in DAS28-ESR (3.4%) was also observed with adalimumab; however, this was not statistically significant .EULAR responses at 6 months were analyzed for 9 medications (as combination or monotherapy): methotrexate, hydroxychloroquine, leflunomide, sulfasalazine, etanercept, adalimumab, tocilizumab, abatacept, and rituximab, with the remaining medications not having sufficient data to record a EULAR response .This study describes the use of cDMARDs/bDMARDs and medication survival in a large cohort of unselected community RA patients. Conventional DMARD usage reflected the contemporary treatment paradigm with methotrexate, hydroxychloroquine, leflunomide, and sulfasalazine being the predominant cDMARDs used. Over one-quarter of patients in this study used leflunomide, which is a higher rate of usage than what has been observed in Europe and North America , 11. ThiTreatment survival was long for all the studied cDMARDs. Methotrexate had the longest treatment survival and appeared to be fulfilling a role as an anchor medication, as it was also the most commonly used medication. The median time on treatment was shorter for bDMARDs compared to cDMARDs. This may be because, in Australia, patients must fail to respond to at least 2 cDMARDs prior to accessibility to government funded bDMARDs. Accordingly, the patient group receiving bDMARDs in Australia are selected as nonresponders and therefore may represent a group with more refractory disease compared to the unselected group of patients receiving cDMARDs. It is to be expected that the response rates in this more refractory group might therefore be reduced. Nevertheless, the bDMARD median survival rates were similar to those seen in an Italian registry cohort .Australian rheumatologists appear to closely follow the EULAR treatment guidelines for use of medications in the treatment of RA . At the The modest reductions in DAS28-ESR over 6 months for the bDMARDs in the OPAL patient cohort appear to be lower than what might have been expected based on previously reported RCTs –18 and oThere are limitations in the ability to make comparisons between drugs in this study. Rather than being randomly allocated, medications were selected based on individual patient comorbidities and clinician perceptions of different medication efficacy/risk profiles. In addition, Australian government rules, which restrict funding support for bDMARDs until there is a documented failure to respond to at least 2 cDMARDs, may also play a role [In conclusion, this longitudinal study in a large cohort of unselected community-based RA patients from OPAL clinics identified that medication choices in the Australian rheumatology clinics were in keeping with international guidelines. One exception was that there appeared to be less use of initial combination cDMARDs therapy. Treatment survival was long in all DMARDs groups studied. The first RA medication changes were escalations from monotherapy methotrexate, cDMARDs other than methotrexate, and bDMARDs. Improvements in disease activity were seen in all DMARDs studied. Initiation of cDMARDs/bDMARDs was associated with disease activity reduction 6 months after commencement of treatment.


To describe our use of intervention mapping as a systematic method to adapt an evidence-based physical activity and nutrition program to reflect the needs of rural Latinas.An intervention mapping process involving six steps guided the adaptation of an evidence based physical activity and nutrition program, using a community-based participatory research approach. We partnered with a community advisory board of rural Latinas throughout the adaptation process.Mujeres Fuertes y Corazones Saludables, within the context of the rural community. A pilot study will be conducted with overweight, sedentary, middle-aged, Spanish-speaking Latinas. Outcome measures will assess change in weight, physical fitness, physical activity, and nutrition behavior.A needs assessment and logic models were used to ascertain which program was the best fit for adaptation. Once identified, we collaborated with one of the developers of the original program  during the adaptation process. First, essential theoretical methods and program elements were identified, and additional elements were added or adapted. Next, we reviewed and made changes to reflect the community and cultural context of the practical applications, intervention strategies, program curriculum, materials, and participant information. Finally, we planned for the implementation and evaluation of the adapted program, The intervention mapping process was feasible and provided a systematic approach to balance fit and fidelity in the adaptation of an evidence-based program. Collaboration with community members ensured that the components of the curriculum that were adapted were culturally appropriate and relevant within the local community context. Obesity, physical inactivity, and diet are associated with increased risk of, and morbidity and mortality from, a range of chronic diseases and certain cancers . In 2015www.thecommunityguide.org). In order to enhance the potential to promote change, behavior change programs need to address differing social and cultural contexts across communities. Implementing an evidence-based intervention (EBI) often involves adaptation in order to fit the local context, including cultural, socioeconomic, and rural/urban factors, to resonate with the local community and enhance effectiveness [One approach to promoting physical activity and healthy eating is the use of individually adapted behavior change programs, which are recommended in The Community Guide  approach and involved community members in the adaptation process to ensure that the evidence-based program was both sensitive and relevant to the local community. For this project, we created a community advisory board (CAB), consisting of five Latinas representing various constituencies in the community . A community member who has worked with one of the researchers for many years invited Latinas living in the community to participate in the project and to be a member of the CAB. In concert with the principles of CBPR, researchers and community members shared equitably in the decision-making process and were involved in all phases of the adaptation and research process.The study took place in a town of nearly 16,000 residents within a rural, agricultural county of Washington State with a population density of 52 people per square mile and Rural-Urban Commuting Area Code (RUCA) of 4.2, meaning a large rural area. In 2010, 82% of the town residents were Latino, 30.5% were foreign born, 73% spoke a language other than English in the home, and 49% had not earned a high school diploma . The medWe describe our application and results for each of the 6 steps in the invervention mapping.Four focus groups were held with Latinas in the community over the course of a year (2011–2012) to elicit their perspectives on determinants of physical activity and healthy eating and to gather intervention ideas. Convenience sampling was used to recruit participants. Latinas who participated in two informal walking groups in the community were invited to participate in a focus group after the completion of a walking group session. All Latinas in each of the two walking groups  agreed to participate. The trained facilitator who held the groups in Spanish took notes during each of the 45-min focus groups. A qualitative researcher identified key determinants from the notes and from a discussion with facilitator. Women whose children had participated in a research study assessing an after school physical activity program were invited to participate in a focus group. Two focus groups were held in English with eight women in one group and six in the second group. The qualitative researcher who led the groups took notes during the groups and identified key determinants from these notes.The focus group resulted in some key findings, such as exercising in a group was a motivator to engage in physical activity. Participants were uncomfortable exercising or walking for exercise in public places, for example in parks. Additionally, participants identified involving family members in exercise and exercising as a family as important. Barriers identified included lack of time, lack of places to be active, and lack of opportunities to be active. Some stated that language was a barrier to using traditional exercise facilities. They wanted to exercise regularly; however, most did not exercise regularly and did not feel confident that they could start and maintain a routine of regular exercise. Participants identified several barriers to healthy eating, including limited access to affordable healthy foods, lack of time, and lack of knowledge in how to prepare healthy meals. Some expressed the belief that healthy foods are tasteless and that they would need to give up the foods they enjoyed in order to be healthy. They voiced interest in an exercise program that included information on healthy eating and, in particular, included cooking classes with healthy recipes.In 2014, we conducted environmental audits, using the Nutrition Environment Measures Survey (NEMS)  to assesThis step involved creating a series of logic models, a visual depiction of the strategies and activities that will lead to change . From a First, we created a logic model of the problem . Next, logic models of change were created  for the three identified evidence-based programs. An additional logic model was developed to delineate how to promote physical activity and healthy eating in this local community. Next, we completed a side-by-side comparison of the logic models to determine which of the three EBIs was the best fit for adaptation considering determinants addressed, behavior change strategies, culture, core elements that cannot be changed, content, delivery, level of evidence, and degree of adaptation needed.Based on this step, SWHH was identified as the most suitable program to adapt for this community of rural Latinas. Pasos Adelante was not suitable, as some of the elements that would need to be adapted were core elements of the program. The culturally tailored aerobics intervention did not address many of the determinants for physical activity and healthy eating identified by the local community. Additionally, it had different performance objectives with the main focus of the program being 60-min classes of vigorous activity delivered three times a week for six months. In comparison, the SWHH program addressed many of the same determinants for physical activity and healthy eating ; it contained similar performance objectives with a focus on both moderate physical activity and healthy eating; and, its core elements  matched key elements needed for the community to change. Thus, SWHH most closely matched the community’s matrix of change and, therefore, would involve the least amount of adaptation to meet this local community’s needs. An example of matching change and performance objectives and behavioral outcomes into a matrix is depicted in Table The developers shared the SWHH curriculum (detailed class-by-class guide) and program leader training manual. Both the CAB members and researchers reviewed the curriculum from a broad perspective looking for key determinants. Next, we identified theoretical methods and program elements or practical applications that needed to be added or adapted . For exaIn this step, the researchers held a series of meetings with the CAB members to examine the class guides (curriculum), participant information sheets, recipes, and the presentation of ideas and messages (including images) and to provide feedback on necessary adaptations to align the curriculum with the local community resources, needs, and culture . This feThe adaptations to the contextual and structural elements took the form of developing and integrating new participant information sheets (handouts), adding additional content to existing information sheets, replacing recipes, increasing exercise options, updating images, and translating all participant materials into Spanish. Each of the individual adaptations fell into at least one of the six adaptation domains: (1) Accessibility, (2) Nutrition Knowledge, 3) Health Knowledge, (4) Skills and Strategies, (5) Address Barriers, and (6) Cultural Relevance  flyers, newspaper advertisements, and radio announcements. Members of the CAB will distribute recruitment materials throughout the community  and attend local events to advertise the program and recruit participants. Inclusion criteria include Spanish-speaking Latinas, ages 40–70 years, inactive (exercise two days or less per week), BMI ≥ 24, and live in the local community. Individuals who meet these criteria will then be screened using the Physical Activity Readiness Questionnaire (PAR-Q), and those with a positive response will require health care provider permission to participate. Exclusion criteria include pregnancy and presence of a health condition precluding moderate to vigorous physical activity.The main outcomes for evaluating the adapted program are weight, cardiorespiratory fitness, physical activity, and dietary behavior. These will be measured at two time points: pre-program (T1) and post-program (T2). Table Process evaluation will occur frequently and in multiple forms throughout the study. After each class, participants and leaders will complete a feedback survey to assess fidelity and feasibility of implementing the adaptations. The leader feedback examines the percentage of participants actively taking part in the exercise, class flow, and feasibility of covering added information during each class. For participants, feedback allows them to share any barriers they face in the class and to reflect on the appropriateness of the adaptations and their receptiveness towards the class curriculum. A mid-program evaluation will be given to the participants to gain further insight into their experiences with the classes. At the start of each class, attendance will be recorded. If necessary, participants will be contacted outside of class by one of the leaders to determine the reason for any reported absences or trends in tardiness. The principal investigator and program leaders will meet each week by phone to address any unanticipated challenges that arise and identify solutions. Results of this pilot study evaluation will be reported separately once completed.We found it feasible to use the intervention mapping process to engage the local community and guide the adaptation of an evidence-based program aimed at obesity prevention through the promotion of physical activity and healthy eating. Intervention mapping employed in this unique way enabled the study team to identify core aspects of the curriculum that needed adaptation while retaining the essential core programmatic evidence-based elements. The adaptations were designed to enhance group cohesion and support for incorporating positive daily nutrition and physical activity based changes within participants’ lives, taking into account the cultural and geographic context. Collaboration with the CAB ensured that the aspects of the curriculum that were adapted were culturally appropriate and relevant to the local community. By collaborating with one of the developers of the original program, we were able to ensure that we maintained the core essential elements and did not alter the underlying logic of the intervention. The intervention mapping process allowed for a systematic and thorough examination of the community context and the program, and served as an effective approach for striking a balance between adaptation to the local context and fidelity to the original program.Cultural adaptation is essential in order to reach and engage diverse cultural communities. A meta-analysis of cultural adaptation studies found that programs were most effective in their treatment implementation when they had a greater number of cultural adaptations targeted to the background and traditions of the population . HoweverWhile cultural adaption is critical given the diversity within the US, adaptation of EBIs beyond cultural considerations have become increasingly important. Adaptation enhances the relevance of a program, increases a program’s reach into the community and alignment with local resources, and addresses barriers and facilitators unique to the community . Other dThere is an inherent tension between fidelity and adaptation, and various approaches for bridging this divide have been used. Despite ongoing debate, maintaining the fidelity of an intervention through the retention of essential core elements has been shown to produce program outcomes that are more similar to those of the original study . There iOur use of intervention mapping as a systematic approach for the adaptation of an EBI provided a guide for a deep dive into the community context and a comprehensive examination of all aspects of the EBI, including implementation and evaluation. This use of intervention mapping contributes to the growing body of research on intervention adaptation by demonstrating that intervention mapping can be re-appropriated and effectively applied to the intervention adaptation process using a community-engaged approach within a community-based setting.