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Background Chronic inflammatory responses initiated by lymphatic injury play a key role in the pathophysiology of secondary lymphedema. However, it is unclear if baseline inflammation or ethnic/racial variability in inflammatory responses increase lymphedema risk. Crown-like structures of the breast (CLS-B), consisting of macrophages engulfing necrotic adipocytes, are a marker of systemic inflammation and have been implicated in the pathogenesis of breast cancer, but their role in lymphedema development is unknown. Here we determine whether baseline differences in inflammation, characterized by the presence of CLS-B, contributed to lymphedema risk in a diverse cohort of patients treated with ALND. Methods Patients ≥ 18 years undergoing ALND were enrolled in a prospective lymphedema screening study. Body mass index (BMI) and volumetric arm measurements (perometer) were performed at baseline, postoperatively, and every 6 months. Breast tissue obtained at definitive surgery was assessed for CLS-B with CD-68 IHC stain in non-tumor breast tissue. Inflammation severity was determined by number of CLS-B/cm2, with the median used to differentiate between mild and severe inflammation. Lymphedema was defined as a relative arm volume change of ≥10%. Lymphedema incidence was assessed using competing risk analysis and compared between patients with and without CLS-B. Uni- and multivariable analysis was performed to identify factors associated with lymphedema development. Results Between 11/2016-03/2020, 304 ALND patients were enrolled; 281 had at least 6 months of follow-up and were included in the study. Eleven percent self-identified as Asian, 20% Black, 6% Hispanic, and 60% White. Median age was 48 years; median BMI was 26.3 kg/m2, with higher BMI observed in Black and Hispanic women compared to Asian and White women (p < 0.001). Overall, 54% had CLS-B, with severe inflammation (> 0.4 CLS-B/cm2) identified in 71 (25%) patients. CLS-B presence correlated with BMI (36% [BMI < 25], 63% [BMI 25-30], 70% [BMI > 30], p < 0.001) and varied across racial/ethnic groups, with a higher prevalence in Black and Hispanic women (68% [Black], 69% [Hispanic] vs 59% [Asian], 46% [White], p = 0.03) (Table). Inflammation severity did not differ by race/ethnicity (p = 0.11). At 2.1 years median follow-up (IQR 1.6-3.1), 66 women developed lymphedema, with a 2-year lymphedema rate of 21.3% (95% CI 16.4-26.8). Lymphedema incidence was higher among Black and Hispanic women, compared to Asian and White women (2-year rate: 33.8% [Black], 31% [Hispanic], 17.4% [Asian], 18.2% [White], p = 0.002), and was higher among women with CLS-B (2-year rate: 28.2% [CLS-B] vs 12.9% [no CLS-B], p = 0.02). On multivariable analysis, Black race (White [referent]: HR 2.85, 95% CI 1.4-5.8; p = 0.03), receipt of NAC (upfront surgery [referent]: HR 2.46, 95% CI 1.04-5.8, p = 0.04) and older age (HR 1.03, 95% CI 1.01-1.06 per 1-year increase; p = 0.009) were independently associated with lymphedema development, while CLS-B was not (HR 1.37, 95% CI 0.81-2.34, p = 0.2). Conclusions In a prospective cohort of patients treated with ALND, Black race, receipt of NAC, and increasing age, but not CLS-B, were independently associated with lymphedema risk. However, the higher CLS-B prevalence in Black women suggests that they may have a propensity for increased inflammation, which may in part be contributing to the higher lymphedema risk observed, but is likely not the only inflammatory mechanism that modulates risk. Table. Clinical characteristics of study cohort stratified by the presence of CLS-B Citation Format: Andrea V. Barrio, Giacomo Montagna, Varadan Sevilimedu, Ethan Gomez, Dilip Giri, Babak Mehrara, Monica Morrow. Does Breast Inflammation Contribute to Lymphedema Risk in Patients Treated with Axillary Lymph Node Dissection? [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-08-09.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

La lectura de la arquitectura de una ciudad permite entender rasgos de su historia, evolución y desarrollo. Especialmente si el lugar cuenta con obras de carácter paradigmático que afianza y aportan a la identidad de su colectivo. Este texto es la sintesis de un estudio, donde se analizaron dos viviendas construidas en Manta-Ecuador entre los años 1960 – 1980, para efectos al presente articulo, se opto por citar solo una. Se pretende demostrar el valor arquitectónico de la vivienda “Cevallos”, que evidencia su función como artefacto cultural, así como la innovación técnica que representa, de manera que la memoria de esta obra y su autor no se pierda. Se llevó a cabo la investigación en tres niveles: exploratorio, descriptivo y deductivo. La metodología aplicada incluye análisis descriptivo, crítico y fenomenológico en base a estudios afines al tema. Como resultado, se comprobó que Manta cuenta con obras arquitectónicas de carácter paradigmática, el problema es la carencia de su conocimiento, el 56% de los encuestados desconocían de su existencia influyendo de manera negativa, dejándolas en el olvido y consigo una muestra de identidad del lugar, en respuesta a la problemática se plantea una matriz para la calificación de una arquitectura paradigmática.

Arsenic is one of the most toxic elements in natural waters since prolonged exposure to this metalloid can cause chronic damage to health.

In this review we present characterization and synthetic chemistry guidelines for obtaining COOH-based alkoxysilanes aiming at SiO2 modification. Applications of these derivatized materials related to biology and medicine are also discussed.

IMPORTANCE: Risk factors for breast cancer–related lymphedema (BCRL) after axillary lymph node dissection (ALND) are poorly understood. OBJECTIVE: To evaluate rates of and risk factors associated with BCRL in a prospective cohort of women treated with ALND. DESIGN, SETTING, AND PARTICIPANTS: This prospective BCRL screening study performed at a tertiary cancer center enrolled women with breast cancer 18 years and older undergoing breast surgery and unilateral ALND in the primary setting or after sentinel lymph node biopsy. EXPOSURES: Risk of BCRL during the first 2 years after ALND and radiotherapy. MAIN OUTCOMES AND MEASURES: Patients were prospectively evaluated with arm volume (perometer) measurements, and BCRL was defined as a relative volume change of 10% or greater from baseline. Cumulative incidence of BCRL was assessed using competing risk analysis. Risk factors for BCRL were assessed on univariate and multivariable analyses. RESULTS: From November 2016 to March 2020, 304 patients were enrolled; 276 had at least 1 longitudinal measurement. Median (IQR) age was 48 (40-57) years; median (IQR) body mass index, calculated as weight in kilograms divided by height in meters squared, was 26.4 (22.5-31.2). Of the 276 patients included in the analysis, 29 (11%) self-identified as Asian, 55 (20%) as Black, 16 (6%) as Hispanic, 166 (60%) as White, and 10 (3%) as unknown race and ethnicity; 70% received neoadjuvant chemotherapy (NAC); 93% received nodal irradiation. The 24-month BCRL rate was 23.8% (95% CI, 17.9%-29.8%), with significant variation by race and ethnicity (24-month rate: 37.2% [Black], 27.7% [Hispanic], 22.5% [Asian], and 19.8% [White]; P = .004). The BCRL rates were also higher among patients receiving NAC vs up-front surgery (24-month rate: 29.3% vs 11.1%; P = .01). On multivariable analysis, Black race and Hispanic ethnicity (compared with White race) (odds ratio [OR], 3.88; 95% CI, 2.14-7.08 and OR, 3.01; 95% CI, 1.10-7.62, respectively; P

The epaulette shark, Hemiscyllium ocellatum, is a small, reef-dwelling, benthic shark that—using its paired fins—can walk, both in and out of water. Within the reef flats, this species experiences short periods of elevated CO2 and hypoxia as well as fluctuating temperatures as reef flats become isolated with the outgoing tide. Past studies have shown that this species is robust (i.e., respiratory and metabolic performance, behavior) to climate change-relevant elevated CO2 levels as well as hypoxia and anoxia tolerant. However, epaulette shark embryos reared under ocean warming conditions hatch earlier and smaller, with altered patterns and coloration, and with higher metabolic costs than their current-day counterparts. Findings to date suggest that this species has adaptations to tolerate some, but perhaps not all, of the challenging conditions predicted for the 21st century. As such, the epaulette shark is emerging as a model system to understand vertebrate physiology in changing oceans. Yet, few studies have investigated the kinematics of walking and swimming, which may be vital to their biological fitness, considering their habitat and propensity for challenging environmental conditions. Given that neonates retain embryonic nutrition via an internalized yolk sac, resulting in a bulbous abdomen, while juveniles actively forage for worms, crustaceans, and small fishes, we hypothesized that difference in body shape over early ontogeny would affect locomotor performance. To test this, we examined neonate and juvenile locomotor kinematics during the three aquatic gaits they utilize—slow-to-medium walking, fast walking, and swimming—using 13 anatomical landmarks along the fins, girdles, and body midline. We found that differences in body shape did not alter kinematics between neonates and juveniles. Overall velocity, fin rotation, axial bending, and tail beat frequency and amplitude were consistent between early life stages. Data suggest that the locomotor kinematics are maintained between neonate and juvenile epaulette sharks, even as their feeding strategy changes. Studying epaulette shark locomotion allows us to understand this—and perhaps related—species’ ability to move within and away from challenging conditions in their habitats. Such locomotor traits may not only be key to survival, in general, as a small, benthic mesopredator (i.e., movements required to maneuver into small reef crevices to avoid aerial and aquatic predators), but also be related to their sustained physiological performance under challenging environmental conditions, including those associated with climate change—a topic worthy of future investigation.

Background To promote ideal cardiovascular health, the American Heart Association recommends adhering to Life's Simple 7 (LS7)—achieving healthy targets for body mass index, physical activity, dietary intake, blood pressure, fasting plasma glucose, and cholesterol, along with smoking abstinence. Poorer achievement of LS7 (lower score) has been associated with the development of hypertension and cardiovascular disease. However, less is known about the associations between LS7 and specific biomarkers linked to cardiovascular health: aldosterone, CRP (C‐reactive protein), and IL‐6 (interleukin‐6). Methods and Results We analyzed 379 individuals (age 18–66 years) from the HyperPATH (International Hypertensive Pathotype), who were maintained on ≥200 mEq of sodium daily for 1 week. We calculated a 14‐point summative LS7 score according to participants' baseline data. Based on the range of LS7 score in this population (3–14), we classified participants as “inadequate” (3–6), “average” (7–10), and “optimal” (11–14). Regression analyses found that a higher LS7 score group was associated with lower levels of serum and urinary aldosterone ( P trend P trend =0.001, respectively), lower plasma renin activity ( P trend P trend =0.023). Being in the “optimal” LS7 score group was associated with lower serum CRP ( P trend =0.001) and IL‐6 ( P trend =0.001). Conclusions A higher LS7 score was associated with a lower activity of the renin‐angiotensin‐aldosterone system and lower levels of the inflammatory markers CRP and IL‐6. These findings offer a possible link between ideal cardiovascular health targets and biomarkers known to play a central role in the development of cardiovascular disease.

Background Nipple-sparing mastectomy is associated with a higher risk of mastectomy skin-flap necrosis than conventional skin-sparing mastectomy. There are limited prospective data examining modifiable intraoperative factors that contribute to skin-flap necrosis after nipple-sparing mastectomy. Methods Data on consecutive patients undergoing nipple-sparing mastectomy between April 2018 and December 2020 were recorded prospectively. Relevant intraoperative variables were documented by both breast and plastic surgeons at the time of surgery. The presence and extent of nipple and/or skin-flap necrosis was documented at the first postoperative visit. Necrosis treatment and outcome was documented at 8–10 weeks after surgery. The association of clinical and intraoperative variables with nipple and skin-flap necrosis was analysed, and significant variables were included in a multivariable logistic regression analysis with backward selection. Results Some 299 patients underwent 515 nipple-sparing mastectomies (54.8 per cent (282 of 515) prophylactic, 45.2 per cent therapeutic). Overall, 23.3 per cent of breasts (120 of 515) developed nipple or skin-flap necrosis; 45.8 per cent of these (55 of 120) had nipple necrosis only. Among 120 breasts with necrosis, 22.5 per cent had superficial, 60.8 per cent had partial, and 16.7 per cent had full-thickness necrosis. On multivariable logistic regression analysis, significant modifiable intraoperative predictors of necrosis included sacrificing the second intercostal perforator (P = 0.006), greater tissue expander fill volume (P < 0.001), and non-lateral inframammary fold incision placement (P = 0.003). Conclusion Modifiable intraoperative factors that may decrease the likelihood of necrosis after nipple-sparing mastectomy include incision placement in the lateral inframammary fold, preserving the second intercostal perforating vessel, and minimizing tissue expander fill volume.

Sequences of CAR T cells with mCD8 signal peptide annotated in orange, scFv annotated in red, myc tag annotated in highlighted gray, mCD28 transmembrane and intracellular annotated in purple, mZeta annotated in green, IRES annotated in pink, mIL12 annotated in black, and m4-1BB annotated in yellow.

(A) Media from in vitro co-culture of CAR T cells with EL4mCD19 tumor cells was assessed for IL12p70 on day 7 after CAR T cell treatment. Data shown is mean +/- s.e.m. of two independent experiments. (B) EL4mCD19 tumor bearing C57BL/6 mice, pretreated with 250mg/kg per mouse of cyclophosphamide day -3, treated i.v. with CAR T cells day 0. Significance determined bylong-rank Mantel-Cox Test, with 95% confidence interval (n=3 per group). *p=0.0224 m1928� compared to m1928� + cyclophosphamide and *p=0.0295 m19� compared to m19� + cyclophosphamide (C) Flow cytometry demonstrating CD25 expression on CAR T cells prior to injection in terms of percentage and representative flow cytometry plot (ns by ordinary one-way ANOVA). Data shown is mean +/- s.e.m. of three independent experiments (n=3 per group). (D) CAR T cells were co-cultured with EL4mCD19 tumor cells and assessed for cytotoxicity 4 hours later, using a luciferase killing assay. m1928�, m19�IL-12, and m1928�IL-12 CAR T cells showed significantly increased cytotoxicity compared to m19� CAR T cells at E:T ratios of 2:1, 1:1, and 0.5:1. There was no difference in tumor lysis between 19�12 and m1928�IL-12 CAR T cells (*p=

(A) CAR T cells were co-cultured with EL4mCD19 tumor cells and then assessed for cytotoxicity 4 hours later, using a luciferase killing assay. There was no difference in tumor lysis between CAR T cells and vex-GFP tagged CAR T cells (two-way ANOVA). Data shown is representative of two independent experiments. (B) Flow cytometry gating strategy to determine CD8+ and CD4+ ratio and PD-1, TIM-3, and LAG-3 inhibitory receptor expression.

T-cell receptor (TCR)–modified T-cell gene therapy can target a variety of extracellular and intracellular tumor-associated antigens, yet has had little clinical success. A potential explanation for limited antitumor efficacy is a lack of T-cell activation in vivo. We postulated that expression of proinflammatory cytokines in TCR-modified T cells would activate T cells and enhance antitumor efficacy. We demonstrate that expression of interleukin 18 (IL18) in tumor-directed TCR-modified T cells provides a superior proinflammatory signal than expression of interleukin 12 (IL12). Tumor-targeted T cells secreting IL18 promote persistent and functional effector T cells and a proinflammatory tumor microenvironment. Together, these effects augmented overall survival of mice in the pmel-1 syngeneic tumor model. When combined with sublethal irradiation, IL18-secreting pmel-1 T cells were able to eradicate tumors, whereas IL12-secreting pmel-1 T cells caused toxicity in mice through excessive cytokine secretion. In another xenograft tumor model, IL18 secretion enhanced the persistence and antitumor efficacy of NY-ESO-1–reactive TCR-modified human T cells as well as overall survival of tumor-bearing mice. These results demonstrate a rationale for optimizing the efficacy of TCR-modified T-cell cancer therapy through expression of IL18.See related commentary by Wijewarnasuriya et al., p. 732

Supplementary Data Figure Legends

(A) CAR T cells, day 5 after infusion, were characterized by flow cytometry in terms of percentage and representative plots. m1928�IL-12 CAR T cells expressed higher levels of inhibitory receptors, PD-1 (*p=0.0015) and LAG-3 (*p=0.0491) and showed a trend toward higher levels of TIM-3 (*p=0.1715). Data obtained is mean +/- s.e.m. of three independent experiments analyzed by unpaired t test. (B) Representative flow cytometry plots of PD-1, LAG-3, and TIM-3 inhibitory receptor expression of CAR T cells referenced in Figure 2B.

(A) B cells were assessed for CD80 expression by flow cytometry through peripheral blood. *p=0.048 unpaired t test of BM and *p=0.0233 unpaired t test of spleen. Data shown is mean +/- s.e.m. of two independent experiments. (B) Luminex data showing IL-4 secreting from EL4mCD19 tumor cells. Data shown is mean +/- s.e.m. of two independent experiments. *p=0.002 by unpaired t test. (C) Flow cytometry demonstrating lack of CD28 expression on CD28-/- T cells. Data shown is representative of two independent experiments. (D) CAR T cells were co-cultured with EL4mCD19 tumor cells and then assessed for cytotoxicity 4 hours later, using a luciferase killing assay. There was no difference in tumor lysis between CD28-/- or wildtype transduced CAR T cells. Data shown is mean +/- s.e.m. of two independent experiments.

Although clinical responses with CD19-targeting chimeric antigen receptor (CAR) T-cell treatment have been observed in patients with certain hematologic malignancies, high rates of disease relapse highlight the necessity to understand and improve mechanisms of CAR T-cell failure. Because T-cell dysfunction is thought to contribute to CAR T-cell treatment failure, understanding what mechanisms drive T cells into this dysfunctional state may aid optimal design of efficacious CAR T cells. Dysfunctional CAR T cells have been characterized as having upregulated inhibitory receptors and decreased cytolytic capabilities. Previous studies have identified a role for sustained CAR CD3ζ signaling in CAR T-cell dysfunction. Here, we demonstrate a mechanism that drives dysfunction in CAR T cells through excessive costimulation. Fully activated CD19-targeted CAR T cells were rendered dysfunctional upon stimulation with both endogenous CD28 stimulation and CAR-mediated CD28 costimulation. Costimulation-driven dysfunction of CAR T cells was demonstrated in a syngeneic immunocompetent mouse model, in which CAR T cells were activated with signals 1 (CD3ζ), 2 (CD28), and 3 (IL12). Thus, we show that CAR T-cell dysfunction can be driven through excessive CD28 and 4-1BB costimulation.See related article by Drakes et al., p. 743

Figure Legends

(A) CAR T cells, day 0 before infusion, were characterized by flow cytometry. Data shown is mean +/- s.e.m. of three independent experiments. "ns" (not significant) by unpaired t test. (B) Representative flow cytometry plots of CAR T cell CD8+ and CD4+ ratios day 5 after infusion referenced in Figure 2D. (C) Representative flow cytometry plots of PD-1, LAG-3, and TIM-3 inhibitory receptor expression of CD8+ CAR T cells referenced in Figure 2E. (D) CAR T cells, day 5 after infusion, were characterized by flow cytometry. m1928�IL-12 CAR T cells, gated on CD8+ T cells, expressed higher levels of double positive inhibitory receptors, LAG-3;TIM-3 (*p=0.0397) and LAG-3;PD-1 (*p=0.001), and showed a trend toward higher levels of TIM-3;PD-1 (*p=0.0563). Data obtained is mean +/- s.e.m. of three independent experiments analyzed by unpaired t test.

Supplementary Figures 1-8

Background Language barriers play significant roles in quality of healthcare. Limited studies have examined the relationships between Spanish language and quality of intrapartum care. The objective was to determine the association between primary Spanish language and quality of intrapartum care so as to further inform best practices for non-English speaking patients in the labor and delivery setting. Methods We used the 2016 Listening to Mothers in California survey data, which included a statewide representative sample of women who gave birth in hospitals. Our analytical sample included 1202 Latina women. Multivariable logistic regression was used to examine the association between primary language (monolingual English vs. monolingual Spanish vs. bilingual Spanish/English) and perceived discrimination due to language, perceived pressure for medical interventions, and mistreatment during labor, adjusting for maternal sociodemographics and other maternal and neonatal factors. Results Over one-third of the study population spoke English (35.6%), less than one-third spoke Spanish (29.1%), and greater than one-third spoke bilingual Spanish/English (35.3%). Overall, 5.4% of Latina women perceived discrimination due to language spoken, 23.1% perceived pressure for any medical intervention, and 10.1% experienced either form of mistreatment. Compared to English-speakers, Spanish-speakers were significantly more likely to report discrimination due to language (aOR 4.36; 95% CI 1.15–16.59), but were significantly less likely to experience pressure for certain medical interventions (labor induction or cesarean delivery) during labor (aOR 0.34; 95% CI 0.15–0.79 for induction; aOR 0.44; 95% CI 0.18–0.97 for cesarean delivery). Bilingual Spanish/English-speakers also significantly reported discrimination due to language to a lesser extent than monolingual Spanish-speakers (aOR 3.37; 95% CI 1.12–10.13). Any form of Spanish language (monolingual or bilingual) was not significantly associated with mistreatment. Conclusions Spanish language may contribute to experiences of discrimination during intrapartum care among Latina women. Future research is needed to explore perceptions of pressure, discrimination and mistreatment, among patients with limited English proficiency.

What does One Health want? Despite its touted interdisciplinarity, to date there has been limited engagement with the social sciences and humanities – in particular with streams of critical social theory that enable a response to this question. In this paper we draw on the critical social sciences to consider how One Health is defined, conceptualized, and positioned, and discuss what we see as vital challenges within One Health that both limit its potential for meaningful change and contribute to a potential for ongoing harm – namely, medicalization, anthropocentrism, and colonial-capitalism. We then advance three areas in the critical social sciences that hold potential for addressing these challenges – feminist, posthuman, and anti-colonial approaches. By doing so we seek to encourage a deeper transdisciplinarity within One Health – one that is open to a genuine engagement with insights from critical social theory and a re-orientation towards more creative and radical re-imaginings in the service of wellbeing for diverse peoples, animals, other beings, and the land.

Background Lithopedion is a term that refers to a fetus that has calcified or changed to bone. The calcification may involve the fetus, membranes, placenta, or any combination of these structures. It is an extremely rare complication of pregnancy and can remain asymptomatic or present with gastrointestinal and/or genitourinary symptoms. Case presentation A 50-year-old Congolese refugee with a nine-year history of retained fetus after a fetal demise was resettled to the United States (U.S.). She had chronic symptoms of abdominal pain and discomfort, dyspepsia, and gurgling sensation after eating. She experienced stigmatization from healthcare professionals in Tanzania at the time of the fetal demise and subsequently avoided healthcare interaction whenever possible. Upon arrival to the U.S., evaluation of her abdominal mass included abdominopelvic imaging which confirmed the diagnosis of lithopedion. She was referred to gynecologic oncology for surgical consultation given intermittent bowel obstruction from underlying abdominal mass. However, she declined intervention due to fear of surgery and elected for symptom monitoring. Unfortunately, she passed away due to severe malnutrition in the context of recurrent bowel obstruction due to the lithopedion and continued fear of seeking medical care. Conclusion This case demonstrated a rare medical phenomenon and the impact of medical distrust, poor health awareness, and limited access to healthcare among populations most likely to be affected by a lithopedion. This case highlighted the need for a community care model to bridge the gap between the healthcare team and newly resettled refugees.

Ca11As10, tetragonal, I4/mmm (no. 139), a = 11.2532(1) Å, c = 16.2351(4) Å, and V = 2055.92(6) Å3, Z = 4, R gt (F) = 0.0347, wR ref (F 2) = 0.0931, T = 150 K.

Delayed single- and few-electron emissions plague dual-phase time projection chambers, limiting their potential to search for light-mass dark matter. This paper examines the origins of these events in the XENON1T experiment. Characterization of the intensity of delayed electron backgrounds shows that the resulting emissions are correlated, in time and position, with high-energy events and can effectively be vetoed. In this work we extend previous S2-only analyses down to a single electron. From this analysis, after removing the correlated backgrounds, we observe rates < 30 events/(electron*kg*day) in the region of interest spanning 1 to 5 electrons. We derive 90% confidence upper limits for dark matter-electron scattering, first direct limits on the electric dipole, magnetic dipole, and anapole interactions, and bosonic dark matter models, where we exclude new parameter space for dark photons and solar dark photons., 20 pages, 17 figures

Background: Patients with early HER2-positive breast cancer (BC) and residual disease after HER2-targeted neoadjuvant chemotherapy (NAC) are at high risk of recurrence. It is estimated that 10-30% of HER2-positive breast cancers change HER2 status after trastuzumab alone, but the effects of adding pertuzumab on this phenomenon and clinical outcomes remain unclear. We previously reported a high rate (~50%) of HER2 status change after HP in a small subset of patients. Herein, we present an updated analysis incorporating pathological review of additional cases.Methods: We identified patients with HER2-positive BC who received NAC with pertuzumab and trastuzumab (NAC-HP) followed by surgery at our institution between September 1, 2013 to November 1, 2019. Patients with HER2 status performed either at MSKCC or outside institutions were included. Change in HER2 status on residual disease from baseline was evaluated. We defined HER2 positivity as immunohistochemistry (IHC) IHC3+ or IHC0-2+ FISH amplified (ratio ≥ 2 or ratio < 2 and HER2 copy number ≥ 6 signals/cell). HER2-low was defined as IHC 1+ or 2+, FISH non-amplified. Disease free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Differences between patients with concordant and discordance HER2 status were assessed using the log-rank test.Results: Of 525 patients receiving NAC with HP, 229 (44%) patients had residual disease post NAC-HP. Among these 229 patients, 141 had both pre and post NAC-HP HER2 status available and were included in this analysis. HER2 status on biopsy specimens was determined at MSKCC in 35/141 (25%) and at external institution in 106/141 (75%). The majority of patients (84%) received dose-dense AC-THP; the remainder received TCHP or other HP-based regimens. Most (96%) of patients continued HP after surgery, and 2 patients received T-DM1. Of the 141 patients, 84/141(60%) were found to be HER2 concordant, while 57 (40%) were found to be HER2 discordant. In 13/57 (23%) patients, HER2 expression was lost (IHC 0), while in 44/57 (77%) patients, HER2-low profile was detected (IHC 1+ in 31, and IHC 2+, FISH non-amplified in 13). Further details are reported in the table. Patients with HER2 discordance after NAC-HP had similar survival outcome compared with patients who remained HER2 concordant (5-years DFS: 92.3% versus 88.7%, p=0.49 and 5-yr OS 93.6% versus 88.4%, p=0.70).Conclusions: In a single center cohort, discordant HER2 status after NAC-HP appeared frequently without statistically significant impact on survival outcome, although this finding may be due to the small size and hence low statistical power. Of these, HER2-low profile is the most frequent post treatment HER2 status change. This raises the possibility that patients with change in HER2 status may have heterogenous expression of HER2 at baseline, and HER2-loss or low sub-clones survive as residual disease due to the selection pressure of HP. Alternatively, anti-HER2 therapy may suppress HER2 expression in surviving cells. These findings could inform studies of tailored approaches in the post-neoadjuvant setting based on the biological profile of residual disease. Pre NAC-HP HER2 statusNPost NAC-HP HER2 statusNDiscordantN=57IHC 3+: 19IHC0: 4IHC1+: 9IHC2+ FISH not ampl: 6IHC 0-2+ FISH ampl: 38IHC0: 9IHC1+: 22IHC2+ FISH not ampl: 7Concordant N= 84IHC 3+: 59IHC 3+: 47IHC 0- 2+ FISH ampl: 12IHC 0-2+ FISH ampl: 25IHC 3+: 4IHC 0- 2+ FISH ampl: 21 Citation Format: Emanuela Ferraro, Anton Safonov, Hanna Y Wen, Edi Brogi, Mithat Gonan, Andrea V. Barrio, Pedram Razavi, Sarat Chandarlapaty, Shanu Modi, Andrew D. Seidman, Larry Norton, Mark E. Robson, Chau T. Dang. Clinical implication of HER2 status change after neoadjuvant chemotherapy with Trastuzumab and Pertuzumab (HP) in patients with HER2-positive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-06.

Increased risk of intestinal dysfunction has been reported in patients after Clostridioides difficile infection (CDI). Enteric glial cells (EGCs), a component of the enteric nervous system (ENS), contribute to gut homeostasis. Previous studies showed that adenosine receptors, A2A and A2B, modulate inflammation during CDI. However, it is unknown how these receptors can modulate the EGC response to the C. difficile toxins (TcdA and TcdB). We investigated the effects of these toxins on the expression of adenosine receptors in EGCs and the role of these receptors on toxin-induced EGC death. Rat EGCs line were incubated with TcdA or TcdB alone or in combination with adenosine analogues 1h prior to toxins challenge. After incubation, EGCs were collected to evaluate gene expression (adenosine receptors and proinflammatory markers) and cell death. In vivo, WT, A2A, and A2B KO mice were infected with C. difficile, euthanized on day 3 post-infection, and cecum tissue was processed. TcdA and TcdB increased A2A and A3 transcripts, as well as decreased A2B. A2A agonist, but not A2A antagonist, decreased apoptosis induced by TcdA and TcdB in EGCs. A2B blocker, but not A2B agonist, diminished apoptosis in EGCs challenged with both toxins. A3 agonist, but not A3 blocker, reduced apoptosis in EGCs challenged with TcdA and TcdB. Inhibition of protein kinase A (PKA) and CREB, both involved in the main signaling pathway driven by activation of adenosine receptors, decreased EGC apoptosis induced by both toxins. A2A agonist and A2B antagonist decreased S100B upregulation induced by C. difficile toxins in EGCs. In vivo, infected A2B KO mice, but not A2A, exhibited a decrease in cell death, including EGCs and enteric neuron loss, compared to infected WT mice, reduced intestinal damage and decreased IL-6 and S100B levels in cecum. Our findings indicate that upregulation of A2A and A3 and downregulation of A2B in EGCs and downregulation of A2B in intestinal tissues elicit a protective response against C. difficile toxins. Adenosine receptors appear to play a regulatory role in EGCs death and proinflammatory response induced by TcdA and TcdB, and thus may be potential targets of intervention to prevent post-CDI intestinal dysmotility.

SUMMARYFemaleAedes aegyptimosquitoes undergo multiple rounds of reproduction, known as gonotrophic cycles. These cycles span the period from blood meal intake to oviposition. Understanding how reproductive success is maintained across gonotrophic cycles allows for the identification of molecular targets to reduce mosquito population growth. Odorant receptor co-receptor (orco) encodes a conserved insect-specific transmembrane ion channel that complexes with tuning odorant receptors (ORs) to form a functional olfactory receptor.orcoexpression has been identified in the male and female mosquito germline, but its role is unclear. We report anorco-dependent, maternal effect reduction in fertility after the first gonotrophic cycle. This decline was rescued by repairing theorcomutant locus. Eggs deposited byorcomutant females are fertilized but the embryos reveal developmental defects, reduced hatching, and changes in ion channel signaling gene transcription. We present an unexpected role for an olfactory receptor pathway in mosquito reproduction.HIGHLIGHTSLoss of theorcoolfactory co-receptor promotes female mosquito fertility decline.After their first reproductive cycle completes,Ae. aegypti orcomutant females produce embryos with disrupted development and reduced hatching.CRISPR/Cas9-mediated repair of theorcomutation rescues the fertility defect.Gene expression profiling of embryos fromorcomutant females supports a role for ion channel signaling in mosquito development.

We present simulated galaxy spectral energy distributions (SEDs) from the far ultraviolet through the far infrared, created using hydrodynamic simulations and radiative transfer calculations, suitable for the validation of SED modeling techniques. SED modeling is an essential tool for inferring star formation histories from nearby galaxy observations, but is fraught with difficulty due to our incomplete understanding of stellar populations, chemical enrichment processes, and the non-linear, geometry dependent effects of dust on our observations. Our simulated SEDs will allow us to assess the accuracy of these inferences against galaxies with known ground truth. To create the SEDs, we use simulated galaxies from the NIHAO suite and the radiative transfer code SKIRT. We explore different sub-grid post-processing recipes, using color distributions and their dependence on axis ratio of galaxies in the nearby universe to tune and validate them. We find that sub-grid post-processing recipes that mitigate limitations in the temporal and spatial resolution of the simulations are required for producing FUV to FIR photometry that statistically reproduce the colors of galaxies in the nearby universe. With this paper we release resolved photometry and spatially integrated spectra for our sample galaxies, each from a range of different viewing angles. Our simulations predict that there is a large variation in attenuation laws among galaxies, and that from any particular viewing angle that energy balance between dust attenuation and reemission can be violated by up to a factor of 3. These features are likely to affect SED modeling accuracy.

BackgroundBeginning in March 2020, health care systems in the United States restricted the number of support people who could be present during pregnancy-related care to reduce the spread of COVID-19. We aimed to describe how SisterWeb, a community-based doula organization that employs Black, Pacific Islander, and Latinx doulas in San Francisco, California, adapted to the COVID-19 pandemic.MethodsAs part of process and outcome evaluations conducted through an academic-community partnership, we interviewed SisterWeb doulas, mentors, and leaders in 2020, 2021, and 2022 (n=26 interviews). We identified preliminary themes using the Rapid Assessment Process and then conducted thematic analysis of data related to COVID-19.ResultsSisterWeb leadership remained committed to safeguarding doulas by shifting to virtual support until doulas were onboarded as benefitted employees. Doulas reported hospital policies impacted clients' pregnancy-related care. Initially, doulas adapted to virtual support by connecting with clients more frequently through phone and text. When permitted to meet in person, doulas adjusted to client preference. Finally, as the pandemic impacted doulas' well-being, they turned to mentors for emotional support.Discussion and health equity implicationsThis analysis contributes to a growing body of literature describing doulas' experiences during the pandemic. By shifting to virtual support, SisterWeb leaders prioritized the health, safety, and financial stability of doulas, who were members of communities disproportionately impacted by COVID-19. Our findings suggest that public health guidance, organizational COVID-19 precautions, and hospital policies hindered SisterWeb's goal of ensuring clients receive equitable medical care. In addition, we found that emotional support for doulas is vital to their work.

We present a catalogue of dynamical properties for 2368 late-type galaxies from the MaNGA survey. The latter complements the catalogue of photometric properties for the same sample based on deep optical DESI photometry processed with AutoProf. Rotation curves (RCs), extracted by model fitting H$\alpha$ velocity maps from the MaNGA Data Analysis Pipeline, extend out to 1.4 (1.9) R$_{e}$ for the primary (secondary) MaNGA samples. The RCs and ancillary MaNGA Pipe3D data products were used to construct various fundamental galaxy scaling relations that are also compared uniformly with similar relations from NIHAO zoom-in simulations. Simulated NIHAO galaxies were found to broadly reproduce the observed MaNGA galaxy population for $\log (M_*/{\rm M_{\odot}) > 8.5}$. Some discrepancies remain, such as those pertaining to central stellar densities and the diversity of RCs due to strong feedback schemes. Also presented are spatially-resolved scatters for the velocity-size-stellar mass (VRM$_*$) structural relations using MaNGA and NIHAO samples. The scatter for these relations in the galaxian interiors is a consequence of the diversity of inner RC shapes, while scatter in the outskirts is dictated by the large range of stellar surface densities which itself is driven by sporadic star formation. The detailed spatially-resolved scatter analysis highlights the complex interplay between local and global astrophysical processes and provides a strong constraint to numerical simulations., Comment: 21 pages, 13 Figures, Accepted for publication in MNRAS

Delphacodes kuscheli Fennah (Hemiptera: Delphacidae) is the main planthopper vector of Mal de R ıo Cuarto virus (MRCV), a Fijivirus that severely affects maize production in Argentina. The effect of several nutritional sources on the virulence of Beauveria bassiana s.l. CEP147 (Balsamo-Crivelli) Vuillemin (Hypocreales: Cordycipitaceae) against this planthopper was evaluated with the aim to select some of them to be incorporated in future mass production studies. Ten agar-agar 2% media were used. Media were supplemented with 10 g of sucrose and 4% flour of either amaranth, chia, flax, oat bran, parboiled rice, poppy, quinoa, or wheat germ. Sabouraud dextrose agar with 1% yeast extract (SDAY) was used as control, and sucrose agar medium supplemented with 2% chitin was used as a possible inductor of enzymatic activity. We evaluated the effect of each medium on colony growth, conidial yield, viability, size, adherence, hydrophobicity, protease activity, cumulative mortality, and median survival time (MST). Principal component analysis indicated that conidial viability and adherence explained the most of the total variance, indicating that these variables can be used as indicators of fungal virulence. Medium supplemented with chia flour not only increased conidial viability (100%) and adherence (0.09 A550) with respect to the control medium, but also produced high D. kuscheli mortality (91.7%), with the lowest MST (5.2 days).We suggest that chia flour, which is rich in carbohydrates, proteins, vitamins, andminerals, might be incorporated as a nutritional supplement to solid substrates in order to increase the virulence of B. bassiana s.l. CEP147 against this and other pests. However, future studies are necessary to evaluate the effectiveness of this nutritional source on solid-state fermentation., Puede accederse a los datos utilizados para este artículo haciendo clic en "Documentos relacionados"., Centro de Investigaciones en Fitopatología, Facultad de Ciencias Naturales y Museo

BACKGROUND: Racial disparities are evident in multiple aspects of the perioperative care of breast cancer patients, but data examining if such differences translate to clinical and patient-reported outcomes are limited. This study examined the impact of race on perioperative outcomes in autologous breast reconstruction. METHODS: A retrospective cohort study including all breast cancer patients who underwent immediate autologous breast reconstruction at a single institution from 2010 to 2017 was conducted. Self-reported race was used to classify patients into 3 groups: white, African American, and other. The primary and secondary endpoints were occurrence of any major complications within 30 days of surgery and patient-reported outcomes (measured with the BREAST-Q), respectively. Regression models were constructed to identify factors associated with the outcomes. RESULTS: Overall, 404 patients, including 259(64%) white, 63(16%) African American, and 82(20%) patients from other minority groups, were included. African American patients had a significantly higher proportion of preoperative comorbidities. Postoperatively, African American patients had a higher incidence of 30-day major complications (p = 0.004) and were more likely to return to the operating room (p = 0.006). Univariable analyses examining complications demonstrated that race was the only factor associated with 30-day major complications (p = 0.001). Patient-reported outcomes were not statistically different at each time point through 3 years postoperatively. CONCLUSIONS: African American patients continue to present with increased comorbidities and may be more likely to experience major complications following immediate autologous breast reconstruction. However, patient-reported satisfaction or physical wellbeing outcomes may not differ between groups.

Reseña de Los pre-textos de La Florida del Inca. Por Inca Garcilaso de la Vega de José Miguel Martínez Torrejón (ed).

Objectives The aims of this study were to experimentally inoculate cats with Cryptosporidium felis oocysts and compare fecal detection by fluorescent antibody assay (FA) and quantitative PCR (qPCR), and document clinical signs associated with infection. Methods Cryptosporidium felis oocysts were concentrated from the feces of a naturally infected cat and orally inoculated into six cats that tested negative for C felis by an FA and fecal flotation (FF). Cats were observed daily for the presence of clinical signs consistent with infection. Fecal samples from all cats on days 0 and 9, and one sample per cat (days 18–21), were evaluated by all assays. On day 31, two cats negative for C felis by FF and FA were administered methylprednisolone acetate and all assays were repeated on days 34, 36 and 38. Samples from all cats were tested by FF and FA on days 41, 43, 45 and 48. Results A total of 41 samples were tested, 25 of which were compared by FA and qPCR. Cryptosporidium felis was detected in 2/25 (8%) and in 19/25 (76%) samples by FA and by qPCR, respectively; the other 16 samples were tested by FF and FA. None of the cats was positive for C felis by FF or FA in samples collected on days 0, 9 or 18–21. One, five and six samples tested positive by qPCR on days 0, 9 and 18–21, respectively. The cats administered methylprednisolone acetate tested positive for C felis by FA on day 36 and by qPCR on days 31, 34, 36 and 38. None of the cats showed clinical signs of disease. Conclusions and relevance Clinical signs were not recognized in any of the cats for the duration of the study. FA was insensitive compared with qPCR for detecting cats with subclinical C felis infection.

Culturally and linguistically diverse (CALD) refugees and immigrants in the United States (U.S.) face barriers to accessing health care, and are more likely to have worse health outcomes as it rela...