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Ovarian cancer (OC) is highly lethal due to late detection and frequent recurrence. Initial treatments, comprising surgery and chemotherapy, lead to disease remission but are invariably associated with subsequent relapse. The identification of novel therapies and an improved understanding of the molecular and cellular characteristics of OC are urgently needed. Here, we conducted a comprehensive analysis of primary tumor cells and their microenvironment from 16 chemonaive and 10 recurrent OC patient samples. Profiling OC tumor biomarkers allowed for the identification of potential molecular targets for developing immunotherapies, while profiling the microenvironment yielded insights into its cellular composition and property changes between chemonaive and recurrent samples. Notably, we identified CD1d as a biomarker of the OC microenvironment and demonstrated its targeting by invariant natural killer T (iNKT) cells. Overall, our study presents a comprehensive immuno-profiling of OC tumor and microenvironment during disease progression, guiding the development of immunotherapies for OC treatment, especially for recurrent disease., Competing Interests: Y.-R.L., D.L., and L.Y. are inventors on patents relating to this manuscript. L.Y. is a scientific advisor to AlzChem and Amberstone Biosciences and a co-founder, stockholder, and advisory board member of Appia Bio. None of the declared companies contributed to or directed any of the writing of this manuscript., (© 2023 The Author(s).)

Herbivorous insects are exceptionally diverse, accounting for a quarter of all known eukaryotic species, but the genomic basis of adaptations that enabled this dietary transition remains poorly understood. Many studies have suggested that expansions and contractions of chemosensory and detoxification gene families-genes directly mediating interactions with plant chemical defenses-underlie successful plant colonization. However, this hypothesis has been challenging to test because the origins of herbivory in many insect lineages are ancient (>150 million years ago (mya)), obscuring genomic evolutionary patterns. Here, we characterized chemosensory and detoxification gene family evolution across Scaptomyza, a genus nested within Drosophila that includes a recently derived (<15 mya) herbivore lineage of mustard (Brassicales) specialists and carnation (Caryophyllaceae) specialists, and several nonherbivorous species. Comparative genomic analyses revealed that herbivorous Scaptomyza has among the smallest chemosensory and detoxification gene repertoires across 12 drosophilid species surveyed. Rates of gene turnover averaged across the herbivore clade were significantly higher than background rates in over half of the surveyed gene families. However, gene turnover was more limited along the ancestral herbivore branch, with only gustatory receptors and odorant-binding proteins experiencing strong losses. The genes most significantly impacted by gene loss, duplication, or changes in selective constraint were those involved in detecting compounds associated with feeding on living plants (bitter or electrophilic phytotoxins) or their ancestral diet (fermenting plant volatiles). These results provide insight into the molecular and evolutionary mechanisms of plant-feeding adaptations and highlight gene candidates that have also been linked to other dietary transitions in Drosophila., Competing Interests: Conflicts of interest statement The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Objective: Primary nitinol stenting (PNS) and drug-coated balloon (DCB) angioplasty are two of the most common endovascular interventions for femoropopliteal atherosclerotic disease. Although many prospective randomized controlled trials have compared PNS or DCB with plain balloon angioplasty (POBA), no studies have directly compared PNS against DCB therapy. The purpose of this network meta-analysis is to determine whether there is a significant difference in outcomes between PNS and DCB., Methods: The primary outcome measure was binary restenosis, the secondary outcome measures were target lesion revascularization (TLR) and change in the ankle-brachial index (ABI). Outcomes were evaluated at 6, 12, and 24 months. A literature review identified all randomized controlled trials published before March 2020 that compared DCB with POBA or PNS with POBA in the treatment of native atherosclerotic lesions of the femoropopliteal artery. Studies were excluded if they contained in-stent stenosis or tibial artery disease that could not be delineated out in a subgroup analysis. Network meta-analysis was performed using the network and mvmeta commands in STATA 14., Results: Twenty-seven publications covering 19 trials were identified; 8 trials compared PNS with POBA and 11 trials compared DCB with POBA. The odds of freedom from binary restenosis for patients treated with DCB compared with PNS at 6 months was 1.19 (95% confidence interval [CI], 0.63-2.22), at 12 months was 1.67 (95% CI, 1.04-2.68), and at 24 months was 1.36 (95% CI, 0.78-2.37). The odds of freedom from TLR for patients treated with DCB compared with PNS at 6 months was 0.66 (95% CI, 0.12-3.80), at 12 months was 1.89 (95% CI, 1.04-3.45), and at 24 months was 1.68 (95% CI, 0.82-3.44). The mean increase in ABI for patients treated with PNS compared with DCB at 6 months was 0.06 higher (95% CI, -0.03 to 0.15), at 12 months was 0.05 higher (95% CI, 0.00-0.09), and at 24 months was 0.07 higher (95% CI, -0.01 to 0.14)., Conclusions: Both DCB and PNS demonstrated a lower rate of binary restenosis compared with POBA at the 6-, 12-, and 24-month timepoints. When comparing DCB with PNS through network meta-analysis, DCB had a statistically lower rate of a binary restenosis and TLR at the 12-month timepoint. This network meta-analysis demonstrates that both DCB and PNS are superior to POBA, and that PNS is a satisfactory substitute for DCB when paclitaxel is not desirable., (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Tunneled dialysis catheter (TDC) use has been associated with increased infectious complications and mortality in hemodialysis-dependent patients. Unfortunately, patients who undergo fistula revisions or creation of a new arteriovenous fistula frequently require a TDC during the postoperative period. Bovine carotid artery grafts (BCAGs) can be used as an early-access dialysis conduit to reduce TDC dependence. This study describes the performance of BCAGs that were cannulated early (<3 days) after implantation and associated clinical outcomes., Methods: BCAGs were implanted in 63 consecutive dialysis-dependent patients. Patients and dialysis centers were directly provided early cannulation instructions; 31 (49%) patients were cannulated early, and of the 31 patients cannulated early, 21 (68%) were cannulated during the first postoperative day. Early complications, primary patency, secondary patency, and TDC incidence were monitored through clinic visits, hospital records, and phone calls to dialysis centers., Results: The primary patency of BCAGs at 1 year in the early and late cannulation cohorts was 28% and 39%, respectively. The secondary patency of BCAGs at 1 year in the early and late cannulation cohorts was 74% and 77%, respectively. Early complications occurred in 11 (19%) patients who received a BCAG. There were no significant differences in complication rates between early and late cannulation patients. Of the 24 patients who underwent the operation without a pre-existing TDC, only three (13%) required TDC placement during the 30-day postoperative period., Conclusions: BCAGs can be cannulated early without increased complication rates or a negative impact on midterm patency. Early cannulation of BCAGs obviates the need for a TDC postoperatively in dialysis-dependent patients undergoing primary vascular access or fistula revision procedures., (Copyright © 2018 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Recent studies have reported successful arteriovenous (AV) fistula maturation rates between 40% and 80%, with older age, distal fistula location, and small vein diameter associated with greater failure rates. Our objective is to determine if these findings are consistent with the outcomes at our institution., Methods: A retrospective chart review was performed on patients who underwent upper extremity AV fistula creation at a single institution. Patient demographics and risk factors were analyzed, as well as fistula location and vein diameter based on preoperative ultrasound. Veins less than 2.5 mm were not used for fistula creation. Successful fistula maturation was defined as the fistula serving as the primary access for hemodialysis for 3 months or greater. Pearson Chi-Square, Fisher's Exact Test, and Mann-Whitney U-tests were used to determine significant associations., Results: Between January 2012 and December 2013, 146 fistulas were created in 136 patients. The median age was 68. Median body mass index (BMI) was 27.8. Ninety-one fistulas were created in men and 55 in women. Ninety-two percent of patients had hypertension, 57% had diabetes, and 33% had coronary artery disease. Sixty percent of fistulas created were brachiocephalic, 24% were basilic vein transpositions, and 16% were radiocephalic. Median vein diameter was 3.7 (range 2.5-8.8). Eighty-four percent of patients were on hemodialysis at the time of fistula creation, and 21% had a prior fistula. One hundred five fistulas were accessed for 3 months or more, resulting in a successful overall maturation rate of 72%. BMI greater than 29.5 (P = 0.026) negatively impacted successful fistula maturation, whereas age, fistula location, and vein size did not., Conclusions: We noted a successful overall maturation rate of 72% at our institution when veins at least 2.5 mm in diameter were used. Our sole negative significant predictor for fistula maturation was BMI greater than 29.5. Therefore, in our experience, age, sex, and fistula location should not be used to preclude patients with a vein diameter of at least 2.5 mm from consideration for AV fistula creation., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Sartorius myoplasty (SM) has been used as an adjunct for soft tissue coverage in vascular groin wound complications. However, the reliability of SM as a primary muscle flap has been questioned. The purpose of this study is to determine the reliability of SM performed by vascular surgeons in the management of vascular groin wound complications. A retrospective review was performed on all patients who underwent SM from 1997 to 2012. The three indications for SM were prophylactic, infection, and noninfectious wound complication. Failure of SM was defined as operative reintervention for bleeding, persistent wound drainage, or infection. A total of 99 patients underwent 103 SM procedures. The patients were 43 per cent male and 57 per cent female; the mean age was 69 years. The indication for SM was infectious in 62 cases (60%), prophylactic in 21 cases (20%), and noninfectious in the remaining 20 cases. Failure of SM occurred in 11 cases (11%). Of these, salvage bypass and/or salvage muscle flap was required in eight cases (73%). When salvage bypass was required, extra-anatomic obturator bypass was performed in 80 per cent of cases. Salvage wound coverage included rectus abdominus flap (60%), rotational flap (20%), and skin grafting (20%).Seventy-three per cent of failures came from the infectious wound group. The most common reason for SM failure was hemorrhage (45%). In 82 per cent of the cases, the sartorius muscle was still viable at reoperation and was used for continued muscle coverage. SM performed by the vascular surgeon provides reliable soft tissue coverage for vascular groin wound complications and should be used as the primary muscle flap in the majority of patients. In cases of SM failure, the vascular surgeon should consider other more extensive muscle flap options.

Enterocyte apoptosis in necrotizing enterocolitis is partly due to the elaboration of toxic intermediates of nitric oxide (NO), such as peroxynitrite (PN). Because p38 mitogen-activated protein kinase (MAPK) and serine-threonine kinase (AKT) are well-characterized pro- and anti-apoptotic mediators, respectively, we hypothesized that PN could induce enterocyte apoptosis via activation of p38 and deactivation of AKT. To test this hypothesis, the rat intestinal cell line, IEC-6, was treated with PN. PN caused phosphorylation of p38, its upstream activator, MKK3/6, and downstream effector, transcription factor ATF-2. PN-induced apoptosis was inhibited by the p38 inhibitor, SB202190, and by p38 siRNA. PN decreased AKT phosphorylation; this effect was abrogated by pre-treatment with SB202190 or p38 siRNA. PN exposure also increased the activity of the protein phosphatase 2A (PP2A). These data demonstrate that PN-mediated apoptosis depends on the p38 pathway and that p38 mediates deactivation of AKT survival pathways possibly by the involvement of PP2A.

Objective: The P300 event-related potential (ERP) is sometimes larger for individuals at low- compared to high-risk for alcoholism. These effects are inconsistent, and how P300 is affected by tobacco smoking in the context of alcoholism risk is unknown. The present study used P300 to examine the inter-relationship between alcoholism heritability and smoking status., Methods: P300 was elicited with a visual discrimination task from young adults at low- and high-risk for alcoholism. Half of the subjects in each risk category reported that they did not smoke cigarettes, and the other half reported that they smoked regularly, with equal numbers of male and female subjects assessed. ERPs were recorded, and subjects were instructed to respond only to an infrequently presented target stimulus that occurred in a series of standard and distracter stimuli., Results: P300 amplitude from the target stimuli was larger for the low-risk compared to high-risk subjects overall. However, smoking status demonstrated even stronger effects, with non-smokers producing consistently larger component amplitudes than smokers and accounting for more variance than alcoholism risk. These group factors also significantly affected P300 scalp topography. No reliable alcoholism risk or smoking group effects were obtained for the ERPs from the other stimuli., Conclusions: The findings suggest that P300 measures of alcoholism risk in young adults are moderated by smoking status. Theoretical implications are discussed.

Objectives: The effects of instructions to refrain from blinking on the P300 event-related brain potential (ERP) from auditory and visual stimuli were assessed., Methods: An oddball paradigm was employed in which young adult subjects (n = 20) silently counted the infrequent target stimuli and were given either no instructions or told "do not blink" in different conditions, with auditory and visual stimulus tasks employed for all subjects. ERPs were recorded from the midline electrodes, with amplitude and latency of the P300 and other components obtained., Results: P300 amplitude for both modalities and target/standard stimulus conditions was smaller and visual peak latency longer in the "do not blink" condition. Blink instructions did not directly affect the other components., Conclusions: Instructions to refrain from blinking can decrease P300 amplitude and can increase peak latency.