Screening for Food Insecurity: A Curriculum for Medical Students.

Introduction: Food insecurity (FI) is defined as a lack of access to enough food for an active, healthy life. We sought to determine how a longitudinal FI screening curriculum impacts medical students' knowledge, attitudes, and behavior in screening for FI. Methods: This was a prospective, single-institution study. The curriculum consisted of three components completed over 3 years. We administered a survey to the intervention cohort before and after the curriculum and analyzed their written reflections. We also evaluated whether students screened for FI during an objective structured clinical exam (OSCE) and compared their performance to a control cohort, which did not receive the curriculum. Results: Preintervention, students felt screening for FI was important for physicians to do with their patients, but most felt uncomfortable addressing it in clinical settings. Postintervention, there was a statistically significant increase in mean scores for knowledge questions (45.24% vs 74.74%, P<.001, pre- and postintervention, respectively). Students also felt more confident in their abilities to screen and follow up about FI. Additionally, compared to the control cohort, the intervention cohort screened for FI more often during their OSCE (28.21% vs 10.71%, P<.001). Conclusion: A longitudinal curriculum using minimal curricular time can improve students' knowledge, attitudes, and behavior when screening for FI. Students who received the curriculum were more likely to recognize the need for and perform FI screening. Based on these findings, we anticipate that the curriculum will increase the likelihood of students identifying, screening for, and intervening in cases of FI in future clinical encounters.

Rewiring of master transcription factor cistromes during high-grade serous ovarian cancer development.

The transcription factors MECOM, PAX8, SOX17 and WT1 are candidate master regulators of high-grade serous 'ovarian' cancer (HGSC), yet their cooperative role in the hypothesized tissue of origin, the fallopian tube secretory epithelium (FTSEC) is unknown. We generated 26 epigenome (CUT&TAG, CUT&RUN, ATAC-seq and HiC) data sets and 24 profiles of RNA-seq transcription factor knock-down followed by RNA sequencing in FTSEC and HGSC models to define binding sites and gene sets regulated by these factors in cis and trans. This revealed that MECOM, PAX8, SOX17 and WT1 are lineage-enriched, super-enhancer associated master regulators whose cooperative DNA-binding patterns and target genes are re-wired during tumor development. All four TFs were indispensable for HGSC clonogenicity and survival but only depletion of PAX8 and WT1 impaired FTSEC cell survival. These four TFs were pharmacologically inhibited by transcriptional inhibitors only in HGSCs but not in FTSECs. Collectively, our data highlights that tumor-specific epigenetic remodeling is tightly related to MECOM, PAX8, SOX17 and WT1 activity and these transcription factors are targetable in a tumor-specific manner through transcriptional inhibitors.

Mantle cell lymphoma presenting as intussuscepting ascending colon mass.

Malignant lymphoma is a rare cause of gastrointestinal intussusception in adults, accounting for less than 1% of all cases of intussusception. This is a case of a South-East Asian woman in her 50s, presenting with intermittent abdominal pain, loose stools and weight loss. CT of the abdomen and pelvis showed an irregular mass causing ileocolic intussusception and she underwent emergency open right hemicolectomy with end ileostomy. Intraoperatively, her bowel was covered with lymphoma nodules, and bulky mesenteric nodules of small bowel and colon were seen. The histology shows mantle cell lymphoma, a rare subtype of B cell non-Hodgkin's lymphoma. She recovered well postoperatively and was started on chemotherapy (Nordic protocol) early.

Study and Implementation of a High-Quality True Sine Wave DC-to-AC Inverter for Solar Power Generation Systems.

True sine wave DC-to-AC inverters are becoming more and more important in solar power generation in order to raise the system's efficiency. A high-quality true sine wave DC-to-AC inverter can be built with a robust intelligent control method. This robust intelligent control method is comprised of improved sliding mode reaching law (ISMRL) and particle swarm optimization (PSO)-catfish effect (CE). The sliding mode reaching law is robust and insensitive to parameter variations and external disturbances. However, it has infinite system-state convergence times and steady-state errors. In addition, solar panels are often affected by partial shading, causing the output power-voltage characteristic curve to be multi-peaked. Such a situation causes misjudgment of the maximum power point tracking with conventional algorithms, which can neither obtain the global extremes nor establish high conversion efficiency. Therefore, this paper proposes an ISMRL based on PSO-CE applied to the tracking of maximum power in the case of partial shading of a solar power generation system. The ISMRL guarantees quick terminable time convergence, making it well-suited for digital implementation. In this paper, PSO-CE is used to find the global best solution of ISMRL, rejecting steady-state errors, slow convergence, and premature trapping in local optimums. Simulation and experimental results are verified using digital implementation based on a Texas Instruments digital signal processor to produce more accurate and better tracking control of true sine wave DC-to-AC inverter-based solar power generation systems.

High-Efficiency Flicker-Free LED Driver with Soft-Switching Feature.

A novel interleaved DC-DC buck converter is proposed to drive high-brightness light-emitting diodes (LEDs). The circuit configuration mainly consists of two buck converters, which are connected in parallel and use interleaved operation. Through interleaved operation, the power capability of the converter is doubled. Traditionally, two individual inductors are used in the two buck converters. The difference between conventional parallel-operated buck converters using two energy storage inductors and the proposed circuit is that the proposed circuit uses two small inductors and a coupled inductor that replace the two inductors of the buck converters. In this way, both buck converters can be designed to operate in discontinuous-current mode (DCM), even if the magnetizing inductance of the coupled inductor is large. Therefore, the freewheeling diodes can achieve zero-current switching off (ZCS). Applying the principle of conservation of magnetic flux, the magnetizing current is converted between the two windings of the coupled inductor. Because nearly constant magnetizing current continuously flows into the output, the output voltage ripple can be effectively reduced without the use of large-value electrolytic capacitors. In addition, each winding current can drop from positive to negative, and this reverse current can discharge the parasitic capacitor of the active switch to zero volts. In this way, the active switches can operate at zero-voltage switching on (ZVS), leading to low switching losses. A 180 W prototype LED driver was built and tested. Our experimental results show satisfactory performance.

Side-to-side versus end-to-side ileocolic anastomosis in right-sided colectomies: A cohort control study.

Aims: The three main types of anastomotic configurations following colorectal resection are Side-to-Side Anastomosis (S-S), End-to-Side Anastomosis (E-S) and End-to-End Anastomosis (E-E). This study aims to present results from a local cohort supplemented by a systematic review with meta-analysis of existing literature to compare the post-operative outcomes between E-S and S-S. Methods: A cohort study of patients who underwent right colectomy with E-S or S-S anastomosis, was conducted at the National University Hospital Singapore. Electronic databases Embase and Medline were systematically searched from inception to 21 August 2020, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Studies were included if they compared post-operative outcomes between E-S and S-S. Results: In the cohort study, 40 underwent E-S and 154 underwent S-S. Both post-operative ileus (12.5% vs. 29.2%, P = 0.041) and length of hospital stay (9.35 days vs. 14.04 days, P = 0.024) favoured E-S, but anastomotic bleed favoured S-S (15.0% vs. 3.2%, P = 0.004). Five studies were included in the meta-analysis with 860 E-S and 1126 S-S patients. Similarly, post-operative ileus (odds ratio [OR] =0.302; 95% confidence interval [CI]: 0.122-0.747; P = 0.010) and length of hospital stay (mean differences = ‒1.54 days; CI: ‒3.00 to ‒0.076 days; P = 0.039) favoured E-S. Additional sensitivity analysis including only stapled anastomosis showed a lower rate of anastomotic leak in E-S patients (OR = 0.185; 95% CI: 0.054-0.627; P = 0.007). Conclusions: This is the first systematic review to show that the E-S technique produces superior post-operative outcomes after right colectomy compared to S-S. However, the choice of anastomosis was largely surgeon dependent, but surgeon factors were not reported.

Predicting master transcription factors from pan-cancer expression data.

Critical developmental "master transcription factors" (MTFs) can be subverted during tumorigenesis to control oncogenic transcriptional programs. Current approaches to identifying MTFs rely on ChIP-seq data, which is unavailable for many cancers. We developed the CaCTS (Cancer Core Transcription factor Specificity) algorithm to prioritize candidate MTFs using pan-cancer RNA sequencing data. CaCTS identified candidate MTFs across 34 tumor types and 140 subtypes including predictions for cancer types/subtypes for which MTFs are unknown, including e.g. PAX8, SOX17, and MECOM as candidates in ovarian cancer (OvCa). In OvCa cells, consistent with known MTF properties, these factors are required for viability, lie proximal to superenhancers, co-occupy regulatory elements globally, co-bind loci encoding OvCa biomarkers, and are sensitive to pharmacologic inhibition of transcription. Our predictions of MTFs, especially for tumor types with limited understanding of transcriptional drivers, pave the way to therapeutic targeting of MTFs in a broad spectrum of cancers.

Single-cell transcriptomics identifies gene expression networks driving differentiation and tumorigenesis in the human fallopian tube.

The human fallopian tube harbors the cell of origin for the majority of high-grade serous "ovarian" cancers (HGSCs), but its cellular composition, particularly the epithelial component, is poorly characterized. We perform single-cell transcriptomic profiling of around 53,000 individual cells from 12 primary fallopian specimens to map their major cell types. We identify 10 epithelial subpopulations with diverse transcriptional programs. Based on transcriptional signatures, we reconstruct a trajectory whereby secretory cells differentiate into ciliated cells via a RUNX3high intermediate. Computational deconvolution of advanced HGSCs identifies the "early secretory" population as a likely precursor state for the majority of HGSCs. Its signature comprises both epithelial and mesenchymal features and is enriched in mesenchymal-type HGSCs (p = 6.7 × 10-27), a group known to have particularly poor prognoses. This cellular and molecular compendium of the human fallopian tube in cancer-free women is expected to advance our understanding of the earliest stages of fallopian epithelial neoplasia.

Transcription factors in epithelial ovarian cancer: histotype-specific drivers and novel therapeutic targets.

Transcription factors (TFs) are major contributors to cancer risk and somatic development. In preclinical and clinical studies, direct or indirect inhibition of TF-mediated oncogenic gene expression profiles have proven to be effective in many tumor types, highlighting this group of proteins as valuable therapeutic targets. In spite of this, our understanding of TFs in epithelial ovarian cancer (EOC) is relatively limited. EOC is a heterogeneous disease composed of five major histologic subtypes; high-grade serous, low-grade serous, endometrioid, clear cell and mucinous. Each histology is associated with unique clinical etiologies, sensitivity to therapies, and molecular signatures - including diverse transcriptional regulatory programs. While some TFs are shared across EOC subtypes, a set of TFs are expressed in a histotype-specific manner and likely explain part of the histologic diversity of EOC subtypes. Targeting TFs present with unique opportunities for development of novel precision medicine strategies for ovarian cancer. This article reviews the critical TFs in EOC subtypes and highlights the potential of exploiting TFs as biomarkers and therapeutic targets.

Short-term impact of surgically induced menopause on cognitive function and wellbeing in women at high risk for ovarian cancer following risk-reducing bilateral salpingo-oophorectomy.

OBJECTIVE: Risk-reducing bilateral salpingo-oophorectomy (RRSO) is an effective strategy to prevent pelvic serous carcinoma for women at high risk of developing ovarian cancer; however, it results in premature menopause. Data is lacking to adequately counsel these women about potential effects of premature menopause on cognition and quality of life. METHODS: A prospective study in premenopausal women at high risk of ovarian cancer to determine changes in cognition over time after RRSO and the impact of hormone therapy (HT) on cognition. Participants were surveyed before and after surgery using the Functional Assessment of Cancer Therapy-Cognitive questionnaire and questions regarding domains of wellbeing at 6, 12 and 18 months. Data was tested for changes across time using mixed model regression and logistic regression. RESULTS: Fifty-seven women were included. Sixty-three percent of participants used HT. At 6 months postoperatively, perceived cognitive impairment declined by 5.5 points overall (4.4 in non-HT users and 6 in HT users), P = 0.003. The other domains of cognition assessed did not change significantly over time and the use of HT did not impact scores. Sleep disruption was common in this cohort and was not mitigated by HT. Self-reported depression improved after RRSO (P = 0.004). CONCLUSION: Women at high risk of ovarian cancer who choose RRSO may experience declines in cognition within the first 6 months of surgical menopause. HT may cause small declines in perceived cognitive impairment at 6 months after RRSO. Women can expect more sleep disruption after menopause, which is not mitigated by HT.

Video Summary:http://links.lww.com/MENO/A697.

Neoadjuvant therapy in locally advanced colon cancer: a meta-analysis and systematic review.

BACKGROUND: The role of perioperative or neoadjuvant chemotherapy for locally advanced colon cancer is unclear. Emerging evidence such as the FOXTROT trial is challenging the conventional norm of upfront operation for these patients. However, these trials have yet to reach statistical significance. METHODS: MEDLINE, Embase, Cochrane Library, China Knowledge Resource Integrated Database (CNKI) and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) and observational studies of patients with locally advanced colon cancer were included. The intervention arm was neoadjuvant chemotherapies while the comparator arm was adjuvant chemotherapies. Studies which reported outcomes of interests included overall survival, disease-free survival, R0 resection rate, perioperative complications and adverse effects of chemotherapy were chosen. RESULTS: We identified five eligible randomized trials and two observational studies, including 29,504 patients. Neoadjuvant therapies exhibited statistically significant improvement in overall survival [hazard ratio (HR) =0.76, 95% confidence interval (CI): 0.65-0.89, P=0.0005], and disease-free survival (HR =0.74, 95% CI: 0.58-0.95, P=0.02). R0 resection rate fell slightly short of significance [odds ratio (OR) =1.86, 95% CI: 0.95-3.62, P=0.07]. Risk of peri-operative complications did not differ between groups when examining abdominal infection [risk ratio (RR) =1.14, 95% CI: 0.59-2.18, P=0.70] and anastomotic leakage (RR =0.83, 95% CI: 0.53-1.31, P=0.42). No statistical differences in complications from chemotherapy were reported. CONCLUSIONS: This meta-analysis highlights the potential survival benefit of neoadjuvant chemotherapy compared to adjuvant chemotherapy for locally advanced colon cancer, without an increase in surgical morbidity. Neoadjuvant or perioperative approaches may be considered an alternative to upfront surgery followed by chemotherapy for locally advanced colon cancer.

Kamikawa Double-Flap Reconstruction After Minimally Invasive Ivor-Lewis Esophagectomy.

Despite the high incidence of reflux esophagitis, there are few reports of antireflux modifications for minimally invasive Ivor-Lewis esophagectomy. We present the case of a 63-year-old man with mid-thoracic esophageal squamous cell carcinoma who underwent minimally invasive Ivor-Lewis esophagectomy after neoadjuvant chemoradiotherapy. Laparoscopic dissection, gastric tube creation, and mobilization was performed. Thoracoscopic esophageal dissection, subcarinal, paraesophageal and diaphragmatic lymphadenectomy were performed, followed by esophagogastric anastomosis with double seromuscular flap reconstruction to recreate the lower esophageal sphincter. The operation was completed in 618 minutes with 200 mL blood loss and the patient recovered uneventfully. A morphologic sphincter was seen on postoperative contrast study.

Ultrasound guided transversus abdominis plane (TAP) block utilization in multimodal pain management after open gynecologic surgery.

Transversus abdominis plane (TAP) block is a peripheral nerve block directed at the nerves in the anterior abdominal wall. We sought to determine whether TAP block reduces post-operative narcotic use or length of stay after open gynecologic surgery. Among 98 women who underwent an open hysterectomy between July 2016 - July 2017 by a gynecologic oncologist, 73 (74.5%) received a TAP block. The majority of patients who received a TAP block had a vertical incision (86.3%) while the majority of patients who did not receive TAP block had a transverse incision (64%). More patients in the TAP block group underwent cancer debulking compared to the no TAP block group (65.7% versus 8%). The two groups did not differ in post-operative pain scores on day 1, 2, or 3, cumulative narcotic use by post-operative day 3, length of stay, or ileus. We found TAP block after vertical skin incision results in comparable pain scores, narcotic use, and length of stay compared to patients undergoing transverse incisions without TAP block.

Survival outcomes following primary tumor resection for patients with incurable metastatic colorectal carcinoma: Experience from a single institution.

OBJECTIVE: Palliative primary tumor resection (PTR) has been used for preventing and treating tumor-related complications. We aimed to determine whether PTR can increase overall survival (OS) in patients with unresectable metastatic colorectal cancer (CRC). METHODS: A retrospective review of a prospectively collected database in a single center was performed. Patients diagnosed with metastatic CRC from January 2004 to December 2014 were included. Patients who had attained curative resection or had disease recurrence were excluded. All patients were discussed at a multidisciplinary tumor board where subsequent treatment decisions were made. RESULTS: Altogether 408 patients were analyzed. Of these 145 received PTR with palliative chemotherapy (PC; group A), 110 received PC only (group B), 52 received PTR only (group C), while 101 received neither PTR nor PC (group D). Undergoing PTR led to statistically significant improvement in OS (22.7 months vs 12.1 months vs 6.9 months vs 2.7 months, P < 0.001). We performed subgroup analyses to control for potential confounders and found that the influence of PTR on OS persisted. With multivariate analysis, the predictors of poor OS were no PTR (hazards ratio [HR] 2.32, 95% confidence interval [CI] 1.82-2.96, P < 0.001), no PC (HR 4.25, 95% CI 3.27-5.33, P < 0.001) and the presence of peritoneal metastases (HR 1.37, 95% CI 1.06-1.78, P = 0.018). Diversion surgery did not lead to a statistical difference in OS. CONCLUSIONS: The absences of PTR and PC, and peritoneal metastases are independently associated with decreased OS in patients with unresectable metastatic CRC. Randomized controlled trials are needed to verify this observation.

Modern-day palliative chemotherapy for metastatic colorectal cancer: does colonic resection affect survival?

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) with surgically incurable metastases would be recommended for palliative chemotherapy (PC). The role of surgical intervention is debatable with no conclusive evidence for routine primary tumour resection (PTR) or stoma creation. We aimed to study if surgical intervention conferred a survival benefit in patients with mCRC who received upfront systemic therapy. METHODS: A retrospective review of a prospectively collected database in a single centre was performed. Patients diagnosed with mCRC from January 2004 to December 2014 were included. We excluded patients who had an upfront surgical intervention, had no treatment with systemic therapy or had attained curative resection. The decision for surgery was based on the outcome of a multidisciplinary tumour board. Demographic, clinicopathological, treatment and follow-up data were collected. Univariate and multivariate analyses were performed. RESULTS: Out of 408 patients with mCRC with incurable metastases, we analysed 124 patients who had upfront PC. Twenty-nine had PC + PTR (group A), 10 had PC + stoma (group B) and 85 had PC only (group C). Undergoing PTR led to significant improvement in overall survival (OS; 30.8 versus 13.4 versus 11.0 months, P < 0.001). With multivariate analysis, undergoing PTR and receiving biologics were independent good prognostic variables. Surgical resection was safe with minimal complications. CONCLUSIONS: PTR was found to increase OS while stoma creation had no impact on OS. The benefits and safety of undergoing PTR may be a result of selection bias. Further prospective studies are required to confirm the observations of this study.

Extent of field change in colorectal cancers with BRAF mutation.

INTRODUCTION: Sporadic colorectal cancers with BRAF mutations constitute two distinct subgroups of colorectal cancers. Recent studies have linked the presence of the BRAF mutation to a familial inheritance pattern. This was a proof-of-concept study that aimed to examine: (a) the extent of field change in sporadic colorectal cancers with BRAF mutation; and (b) the extent of resection margins required and the pattern of DNA mismatch repair protein loss in these tumours. METHODS: Eight microsatellite instability-high tumours with positive BRAF mutation from an existing histopathological database were selected for BRAF mutation and mismatch repair protein analysis. RESULTS: All the resection margins were negative for BRAF mutation. Three tumours had loss of MLH1 and PMS2 expressions, and five tumours had no protein loss. Six peritumoral tissues were negative and one was positive for BRAF mutation. CONCLUSION: The results suggest that any early field change effect is restricted to the immediate vicinity of the tumour and is not a pan-colonic phenomenon. Current guidelines on resection margins are adequate for BRAF mutation-positive colorectal cancers. Any suggestion of a hereditary link to these tumours is likely not related to germline BRAF gene mutations. The pattern of protein loss reinforces previous findings for the two subgroups of BRAF mutation-positive colorectal cancers.

Hypertrophy changes 3D shape of hiPSC-cardiomyocytes: Implications for cellular maturation in regenerative medicine.

Advances in the use of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes for heart regeneration and in vitro disease models demand a greater understanding of how these cells grow and mature in 3-dimensional space. In this study, we developed an analysis methodology of single cardiomyocytes plated on 2D surfaces to assess their 3D myofilament volume and its z-height distribution, or shape, upon hypertrophic stimulation via phenylephrine (PE) treatment or long-term culture ("aging"). Cardiomyocytes were fixed and labeled with α-actinin for confocal microscopy imaging to obtain z-stacks for 3D myofilament volume analysis. In primary neonatal rat ventricular myocytes (NRVMs), area increased 72% with PE, while volume increased 31%. In hiPSC-cardiomyocytes, area increased 70% with PE and 4-fold with aging; however, volume increased significantly only with aging by 2.3-fold. Analysis of z-height myofilament volume distribution in hiPSC-cardiomyocytes revealed a shift from a fairly uniform distribution in control cells to a basally located volume in a more flat and spread morphology with PE and even more so with aging, a shape that was akin to all NRVMs analyzed. These results suggest that 2D area is not a sufficient measure of hiPSC-cardiomyocyte growth and maturation, and that changes in 3D volume and its distribution are essential for understanding hiPSC-cardiomyocyte biology for disease modeling and regenerative medicine applications.