bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxaliplatin plus irinotecan vs irinotecan as second-line treatment in pancreatic cancer patients: a randomized–controlled open-label Phase II study
Authors: Zhang Hangyu , Tong Zhou , Liu Lulu , Fu Qihan , Zhu Xudong , Dai Xiaomeng , Bao Xuanwen , Fang Weijia , Zheng Yi , Zhao Peng
Published: February 2023

Background

Limited second-line therapeutic options are available for metastasis pancreatic cancer (mPC). We aimed to explore the efficacy and safety of oxaliplatin plus irinotecan (IROX) in mPC patients.

Methods

This is an open-label, Phase 2, randomized study of mPC patients (aged 18–75 years) who failed when using gemcitabine plus S-1 as first-line therapy. Block randomization with a block size of four was used to randomly assign patients (1:1) between October 2015 and December 2017 to receive either IROX (oxaliplatin 85 mg/m2 and irinotecan 160 mg/m2) or irinotecan monotherapy (irinotecan 180 mg/m2) until disease progression, unacceptable adverse events, or consent withdrawal. The primary end point was overall survival, and the secondary end points were progression-free survival, overall response rate, and adverse event rate.

Results

A total of 74 patients were enrolled in this study, including 44 males and 30 females, with an average age of 61 years. The median overall survival was 10.2 and 6.7 months (adjusted hazard ratio [HR], 0.7; 95% confidence interval [CI], 0.4–1.2; P = 0.20) and the median progression-free survival was 5.1 and 2.3 months (adjusted HR, 0.4; 95% CI, 0.2–0.6; P < 0.01) in the IROX group and irinotecan group, respectively. The overall response rates were 18.4% (7/38) in the IROX group and 5.5% (2/36) in the irinotecan group (P = 0.06). Grade 3–4 adverse events occurred in 34% (13/38) of patients in the IROX group and 19% (7/36) of patients in the irinotecan group (P = 0.15).

Conclusions

IROX had no significant survival benefit over irinotecan monotherapy in our study. However, IROX reduced the risk of disease progression by 60%, with acceptable toxicity.
Microbial Dynamics in Newly Diagnosed and Treatment Naïve IBD Patients in the Mediterranean
Authors: Rausch Philipp , Ellul Sarah , Pisani Anthea , Bang Corinna , Tabone Trevor , Marantidis Cordina Claire , Zahra Graziella , Franke Andre , Ellul Pierre
Published: February 2023

Background

Microbial communities have long been suspected to influence inflammatory processes in the gastrointestinal tract of patients with inflammatory bowel disease. However, these effects are often influenced by treatments and can rarely be analyzed in treatment-naïve onset cases. Specifically, microbial differences between IBD pathologies in new onset cases have rarely been investigated and can provide novel insight into the dynamics of the microbiota in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Fifty-six treatment-naïve IBD onset patients (67.3% CD, 32.7% UC) and 97 healthy controls were recruited from the Maltese population. Stool samples were collected after diagnosis but before administration of anti-inflammatory treatments. Fecal microbial communities were assessed via 16S rRNA gene sequencing and subjected to ecological analyses to determine disease-specific differences between pathologies and disease subtypes or to predict future treatment options.

Results

We identified significant differences in community composition, variability, and diversity between healthy and diseased individuals—but only small to no differences between the newly diagnosed, treatment-naïve UC and CD cohorts. Network analyses revealed massive turnover of bacterial interactions between healthy and diseased communities, as well as between CD and UC communities, as signs of disease-specific changes of community dynamics. Furthermore, we identified taxa and community characteristics serving as predictors for prospective treatments.

Conclusion

Untreated and newly diagnosed IBD shows clear differences from healthy microbial communities and an elevated level of disturbance, but only the network perspective revealed differences between pathologies. Furthermore, future IBD treatment is to some extent predictable by microbial community characteristics.
Morphology of pig nasal structure and modulation of airflow and basic thermal conditioning
Authors: Yuk Jisoo , Akash Mohammad Mehedi Hasan , Chakraborty Aneek , Basu Saikat , Chamorro Leonardo P , Jung Sunghwan
Published: February 2023

Mammals have presumably evolved to adapt to a diverse range of ambient environmental conditions through the optimized heat and mass exchange. One of the crucial biological structures for survivability is the nose, which efficiently transports and thermally preconditions the external air before reaching the internal body. Nasal mucosa and cavity help warm and humidify the inhaled air quickly. Despite its crucial role, the morphological features of mammal noses and their effect in modulating the momentum of the inhaled air, heat transfer dynamics, and particulate trapping remain poorly understood. Tortuosity of the nasal cavity in high-olfactory mammalian species, such as pigs and opossum, facilitates the formation of complex airflow patterns inside the nasal cavity, which leads to the screening of particulates from the inhaled air. We explored basic nasal features in anatomically realistic nasal pathways, including tortuosity, radius of curvature, and gap thickness; they show strong power-law correlations with body weight. Complementary inspection of tortuosity with idealized conduits reveals that this quantity is central in particle capture efficiency. Mechanistic insights into such nuances can serve as a tipping point to transforming nature-based designs into practical applications. In-depth characterization of the fluid–particle interactions in nasal cavities is necessary to uncover nose mechanistic functionalities. It is instrumental in developing new devices and filters in a number of engineering processes.
Supranational or cooperative? Rethinking the African Continental Free Trade Area Agreement Competition Protocol institutional design
Authors: Kigwiru Vellah Kedogo
Published: February 2023

African countries are currently negotiating the African Continental Free Trade Area (AfCFTA) Competition Protocol (CP) to regulate competition in the created continental market. However, the most daunting task for the negotiators and African countries is which institutional design to adopt at the continental level, pitying against a supranational or cooperative institutional model. Drawing from a dearth of literature on institutional designs, I propose two factors that African countries should consider when deciding on the most appropriate institutional design for the AfCFTA CP. First are the benefits and costs of each institution design building on the experiences of existing regional competition regimes. Second is the institutional context in which the AfCFTA Continental Competition Regime (CCR) will be established, which constitutes African countries’ attitudes towards supranational institutions, preference heterogeneity, and power distributions. The findings of this article show that African countries should establish a less ambitious institution design that will attract business and political acceptance.
Wet-food diet promotes the recovery from surgery of castration and control of body weight in adult young cats
Authors: Bian Zhaowei , Jian Xiaoying , Liu Guanbao , Jian Shiyan , Wen Jiawei , Zhang Han , Lin Xinye , Huang Hongcan , Deng Jinping , Deng Baichuan , Zhang Lingna
Published: February 2023

Inappropriate dietary management may lead to delayed recovery from castration surgery and significant weight gain in cats after castration. Wet canned food often exhibits more advantageous characteristics than dry food (e.g., higher palatability and digestibility, and lower energy density). This study compared the effects of canned and dry food on surgical recovery and weight management in cats after castration. Eighteen healthy cats (weighed 4.33 ± 1.04 kg and aged 18-months old) were allocated to one of the two dietary treatments (N = 9/group), dry (CON) and canned food (CAN) balanced for sex and initial BW. Cats were fed ad libitum for 7 weeks, including one week before surgery (week 0) and 6 weeks after surgery (week 1–6). Daily dry matter intake (DMI), and weekly body weight (BW) and body condition score (BCS) was obtained. Feces were collected for measuring nutrient digestibility and concentrations of short-chain fatty acids (SCFA) and branched-chain fatty acids (BCFA). Physical pain and wound surface assessment were performed at week 1. Blood was also collected intermittently for measuring biochemical indices and untargeted metabolomics analysis. Results indicated that BW, BCS and daily DMI in CON group increased (P < 0.05) over time after castration, but were maintained relatively stable in CAN group. Cats in CAN group exhibited less pain-related behavior as reflected by lower score of comfort (P < 0.05) and vocalization (P < 0.10), improved wound surface assessment (P < 0.10), lower level of lipase (P < 0.10) and ratio of blood urea nitrogen/serum creatinine (BUN/SC; P < 0.05), and higher level of superoxide dismutase (SOD; P < 0.05) in week 1 than CON cats. Meanwhile, the CAN group had significantly higher concentration of immunoglobulin G (IgG) on days 5 and 7, and higher level of high-density lipoprotein cholesterol (HDL-C; P < 0.10) but lower triglyceride (TG; P < 0.05) than CON group on day 20 and 48. Fecal total and most individual SCFA increased significantly from week 1 to week 6 regardless of diet, but the increase of butyric acid over time only occurred in CON group (P < 0.05). Also, serum metabolomic analysis revealed differential metabolic pathways between the two groups. Overall, compared with the dry food, the canned food tested in our study promoted cat wound recovery by reducing pain and increasing immune and antioxidative capacity after sterilizing surgery, and helped to maintain healthy body condition in cats after castration.
Burn Injury From Smoking Electronic Cigarettes While on Supplemental Oxygen
Authors: Montoya Ana , Ozhathil Deepak , Hollowed Kathleen , Kahn Steven A
Published: February 2023

Many reports pertaining to burns from e-cigarette battery explosions exist, as do injuries from smoking conventional cigarettes while on home-oxygen therapy. However, literature regarding burn injuries from e-cigarettes while on oxygen therapy is limited. The heating coil of the device can rise to temperatures that facilitates ignition of oxygen. The purpose of this study is to describe and characterize this novel and under-reported mechanism of injury. This study was a descriptive review of 2013–2016 National Burn Repository (NBR) data, with a query for “oxygen,” “O2,” “electronic cigarettes,” and various permutations/abbreviations/misspellings. Demographics, injury characteristics, and outcomes were reported. Also, a Google search for lay-press articles and a PubMed/Scopus search using similar terms was conducted to find literature. Of approximately 60,000 NBR entries, 8 records of injury while smoking e-cigarettes on oxygen were found. Patients were predominantly male, 63 ± 9 years old, with 3.4% ± 4 TBSA burns, and LOS of 5.8 ± 7 days (an LOS O/E ratio of 1.5). Two patients sustained full-thickness burns (0.5% and 11% TBSA). Three were intubated, with mean of 3.33 ventilator-days. Most injuries occurred at home (88%). All patients survived. A google search revealed five lay-press articles. Only three partially relevant scientific articles were found to only mention the phenomenon, without granular data. Although uncommon, smoking e-cigarettes on supplemental oxygen can result in injury without a lithium-ion battery explosion. Limitations in the database may have resulted in underestimation of injuries. A paucity of relevant literature exists, necessitating more research. Patients who receive home-O2 should be warned about this potential danger.
The Impact of Systematic Insecticides Against Emerald Ash Borer on Phenology of Urban Ash Trees
Authors: Mwangola Dorah M , Kees Aubree M , Grosman Donald M , Aukema Brian H
Published: February 2023

The continued threat of emerald ash borer (Agrilus planipennis; EAB) to North American ash trees (Fraxinus spp.) has necessitated the use of systemic insecticide treatments as a primary control strategy against EAB in urban centers. Altered tree phenology due to systemic insecticides could mediate nontarget effects on other insect species, such as seed weevils or leaf-feeders, but whether such injections alter phenological events has not been studied. This study assessed the effects of systemic injections of emamectin benzoate or azadirachtin relative to untreated controls on the spring and fall phenology of mature green ash trees in Saint Paul, MN, USA from fall 2017 to spring 2019. EAB was first detected in this area in 2009. Trees showed minor, visible signs of EAB infestation at study initiation, but not mortality. We examined six phenological events: bud swelling, budburst, flowering, leaf out, leaf color change, and leaf abscission using a visual survey protocol. The timing of phenological events was similar across the different treatments for all but two of events; budburst and flowering. Budburst and flowering occurred 7 d and 5 d earlier, respectively, in treated trees than untreated trees. Given symptoms observed, we posit that delays in these events in untreated trees were due to infestations of EAB and the treatments of emamectin benzoate or azadiractin simply preserved the original phenology. The results from this study suggest that systemic insecticides may mitigate changes in ash tree phenology such as delayed leaf out that may be early symptoms of emerald ash borer.
Cockroaches as Trojan Horses for Control of Cockroach Aggregations With Baits
Authors: Hamilton Jamora A , Wada-Katsumata Ayako , Schal Coby
Published: February 2023

Gel bait formulations of insecticides have been shown to be highly effective in managing German cockroach (Blattella germanica L. [Blattodea: Ectobiidae]) populations. Three potential reasons for this are high palatability of baits, the use of slow-acting insecticides, and their horizontal transfer within aggregations, a phenomenon known as ‘secondary mortality’. Our objective was to determine whether horizontal transfer can go beyond secondary, to tertiary and quaternary effects, and to compare various gel baits with different active ingredients. We fed adult females a bait and recorded their bait consumption, moribundity, and mortality. Groups of first instars were then exposed to the dead females and their feces, secondary mortality was quantified, and a new cohort of nymphs was then exposed to the feces and dead nymphs (for tertiary mortality); this process was repeated for quaternary mortality. This design did not distinguish among the major mechanisms of horizontal transfer of insecticides, namely coprophagy and contact with feces, exposure to regurgitated fluids, and cannibalism and necrophagy of nymphs. All the tested baits caused 100% mortality of the adult females that directly fed on the bait and high secondary mortality (average of >85%) within 48 hr. Baits containing either dinotefuran, emamectin benzoate, fipronil, or indoxacarb caused tertiary mortality (average of 15–70%), but only the fipronil and indoxacarb baits caused some quaternary mortality. The relative importance of secondary, tertiary, and quaternary transfer of the active ingredient remains to be determined in field populations of the German cockroach.
The Human Cost of Collusion: Health Effects of a Mexican Insulin Cartel
Authors: Barkley Aaron
Published: February 2023

Despite recent attention to the role of competition in determining health outcomes in developed nations, little is known about how market power impedes access to quality care in lower-income countries. This paper studies the effects of policy changes that stopped collusion among firms supplying insulin to one of Mexico’s largest health care providers. I document increased insulin utilization and decreased diabetes complications and mortality following the sudden drop in insulin prices caused by the cartel’s collapse. These adverse health outcomes expand the assessment of damages caused by the cartel. The findings highlight the importance of market design policies in health markets, particularly for low- and middle-income countries.
Precision Ephemerides for Gravitational-wave Searches – IV. Corrected and refined ephemeris for Scorpius X-1
Authors: Killestein T L , Mould M , Steeghs D , Casares J , Galloway D K , Whelan J T
Published: February 2023

Low-mass X-ray binaries have long been theorized as potential sources of continuous gravitational-wave radiation, yet there is no observational evidence from recent LIGO/Virgo observing runs. Even for the theoretically ‘loudest’ source, Sco X-1, the upper limit on gravitational-wave strain has been pushed ever lower. Such searches require precise measurements of the source properties for sufficient sensitivity and computational feasibility. Collating over 20 yr of high-quality spectroscopic observations of the system, we present a precise and comprehensive ephemeris for Sco X-1 through radial velocity measurements, performing a full homogeneous re-analysis of all relevant data sets and correcting previous analyses. Our Bayesian approach accounts for observational systematics and maximizes not only precision, but also the fidelity of uncertainty estimates – crucial for informing principled continuous-wave searches. Our extensive data set and analysis also enables us to construct the highest signal-to-noise ratio, highest resolution phase-averaged spectrum of a low-mass X-ray binary to date. Doppler tomography reveals intriguing transient structures present in the accretion disc and flow driven by modulation of the accretion rate, necessitating further characterization of the system at high temporal and spectral resolution. Our ephemeris corrects and supersedes previous ephemerides, and provides a factor three reduction in the number of templates in the search space, facilitating precision searches for continuous gravitational-wave emission from Sco X-1 throughout the upcoming LIGO/Virgo/KAGRA O4 observing run and beyond.
Orienting to Pedagogical Service
Authors: Kim Catrina S
Published: February 2023

This essay considers the Society for Music Theory’s valuations of research, service, and pedagogy in light of Sara Ahmed’s (2006) reflections on orientation and labor. Ahmed’s description of the philosopher’s writing table turns attention to the domestic labor that creates the conditions for the very work of philosophizing; by bringing this analysis to bear on Stephen Lett’s “Making a Home of The Society for Music Theory, Inc.” (2023), this article brings the following question to the fore: What sorts of labor are “relegated to the background” of the SMT members’ own “writing tables”? This article thus extends Lett’s metaphor of the SMT’s homemaking practices, questions the meaning of service through the lens of pedagogy and research, and highlights the role of academic contingent labor within this network.
Who Does the Society for Music Theory Gather?
Authors: VanHandel Leigh
Published: February 2023

An important question in Stephen Lett’s provocative article is K’eguro Macharia’s, “Who is gathered by your invitation?” (2021). Lett outlines how the founders of the Society for Music Theory staked out territory for the discipline to establish theorists as separate from composers, musicologists, and pedagogues, and how they assessed who was to be invited by determining what theory as a discipline was and what it was to be. He then discusses how others have been (and still are) invited or excluded based on principles present since the founding of the society and offers suggestions for how to make SMT as an institution more welcoming by using the ideas of homemaking and world-building. My response addresses two topics: first, that the narrow view of the discipline of music theory present at its inception created an anti-pedagogy bias that exists to this day; and second, that this narrow view is perpetuated by graduate programs, which can and should be changed in order to achieve the goal of diversification of the discipline and its members.
Integrative analysis of ferroptosis regulators for clinical prognosis based on deep learning and potential chemotherapy sensitivity of prostate cancer
Authors: Guo Tuanjie , Yuan Zhihao , Wang Tao , Zhang Jian , Tang Heting , Zhang Ning , Wang Xiang , Chen Siteng
Published: February 2023

Exploring useful prognostic markers and developing a robust prognostic model for patients with prostate cancer are crucial for clinical practice. We applied a deep learning algorithm to construct a prognostic model and proposed the deep learning-based ferroptosis score (DLFscore) for the prediction of prognosis and potential chemotherapy sensitivity in prostate cancer. Based on this prognostic model, there was a statistically significant difference in the disease-free survival probability between patients with high and low DLFscore in the The Cancer Genome Atlas (TCGA) cohort (P < 0.0001). In the validation cohort GSE116918, we also observed a consistent conclusion with the training set (P = 0.02). Additionally, functional enrichment analysis showed that DNA repair, RNA splicing signaling, organelle assembly, and regulation of centrosome cycle pathways might regulate prostate cancer through ferroptosis. Meanwhile, the prognostic model we constructed also had application value in predicting drug sensitivity. We predicted some potential drugs for the treatment of prostate cancer through AutoDock, which could potentially be used for prostate cancer treatment.
Virgin territory
Authors: McKenzie Christopher
Published: February 2023

The British Virgin Islands has recently introduced a substantial number of reforms in relation to trusts and estates. These have been made in addition to those innovations relating to variation, reservation of powers and the jurisdiction’s firewall offering, which are considered in earlier articles in this periodical.1 These further reforms include those enabling foreign grants of representation to be resealed in the jurisdiction, the reintroduction of ‘the old rule in Hastings–Bass’ and refinements to the territory’s highly popular private trust company offering.
FIRE Mimics a 14-3-3–Binding Motif to PromotePhytophthora palmivoraInfection
Authors: Evangelisti Edouard , Guyon Alex , Shenhav Liron , Schornack Sebastian
Published: February 2023

The oomycete Phytophthora palmivora infects a wide range of tropical crops worldwide. Like other filamentous plant pathogens, it secretes effectors to colonize plant tissues. Here, we characterize FIRE, an RXLR effector that contains a canonical mode I 14-3-3 phospho-sensor–binding motif that is conserved in effectors of several Phytophthora species. FIRE is phosphorylated in planta and interacts with multiple 14-3-3 proteins. Binding is sensitive to the R18 14-3-3 inhibitor. FIRE promotes plant susceptibility and co-localizes with its target around haustoria. This work uncovers a new type of oomycete effector target mechanism. It demonstrates that substrate mimicry for 14-3-3 proteins is a cross-kingdom effector strategy used by both prokaryotic and eukaryotic plant pathogens to suppress host immunity.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Luck, an Inquisitive Mind, and Opportunities: Lessons Learned: A Blinded Study of Pulse Oximetry before It Became a Standard of Care
Authors: Coté Charles J.
Published: February 2023

A Single-blind Study of Pulse Oximetry in Children. By CJ Coté, EA Goldstein, MA Cote, DC Hoaglin, and JF Ryan. Anesthesiology 1988; 68:184–8. Reprinted with permission.

Oxygen saturation determined by pulse oximetry was monitored in 152 pediatric surgical patients divided into two groups. In one group, the oximeter data and alarms were available (N = 76) to the anesthesia team, and, in the other group, these data were unavailable (N = 76). A trained observer recorded all intraoperative hypoxic episodes and informed the anesthesia team of all major events (i.e., oxygen saturation 85% or less for 30 s or more; Pao
2, approximately 52 mmHg). Thirty-five major events occurred: 24 in the unavailable group, and 11 in the available group (P = 0.021). A greater number of major events occurred in children 2 yr or younger (P = 0.013). Hypoxic events diagnosed by the oximeter, but not by the anesthesiologist, were more frequent in the unavailable group (13) than in the available group (5; P = 0.0495). American Society of Anesthesiologists (Schaumburg, Illinois) Physical Status III and IV patients were more likely to suffer a major event (P = 0.009 available, 0.006 unavailable). The pulse oximeter diagnosed hypoxemia before the signs and symptoms of hypoxemia were apparent (i.e., before observed cyanosis or bradycardia). Major hypoxic events were unrelated to duration of anesthesia. Major events were evenly distributed among induction, maintenance, and awakening from anesthesia; a greater number of hypoxic events occurred during induction in the unavailable group (P = 0.031). No morbidity was documented in any patient who suffered a hypoxic event. More patients experienced borderline oxygenation in room air at the end of anesthesia (90% saturation or less) in the unavailable group (12 of 60) than in the available group (3 of 57; P = 0.009). The authors conclude that pulse oximetry, in contrast to changes in vital signs, does provide an early warning of developing hypoxemia in anesthetized children.
Addressing the National Crisis Facing Black and Latina Women, Birthing People, and Infants: The Maternal and Child Health Equity Summit
Authors: Krishnamoorthi Mahima , Balbierz Amy , Laraque-Arena Danielle , Howell Elizabeth A.
Published: February 2023

To address the national crisis of maternal and infant health disparities, especially outcomes experienced by Black and Latina women and birthing people, The New York Academy of Medicine, the Icahn School of Medicine at Mount Sinai, the Blavatnik Family Women’s Health Research Institute, and the University of Pennsylvania Health System and Perelman School of Medicine hosted the Maternal and Child Health Equity Summit. The primary purpose of the summit was to disseminate findings to a national audience of two National Institutes of Health–funded mixed-methods studies that investigated the contribution of hospital quality to disparities in maternal and infant Health in New York City (R01MD007651 and R01HD078565). In addition, the summit showcased factors in maternal and infant health inequity from leading diverse experts in both fields and identified outstanding challenges to reducing maternal and infant morbidity and mortality disparities and strategies to address them. Summit presenters and participants identified five primary areas of focus in proposed clinical actions and approaches for maternal and neonatal health care based on discussions during the summit: 1) quality and standardization of care; 2) adjustment of care strategy based on patient-reported experience; 3) health care professional and institutional accountability to patients; 4) commitment to building trust; and 5) anti-racism practices in education, training, and hiring. Recommendations from this conference should inform hospital care and public policy changes and frame a national agenda to address perinatal health disparities for Black, Indigenous, and other women and birthing people of color.
Fluorescein Mapping in Vulvar Paget Disease
Authors: Wagar Matthew K. , Zhang Ran Catherine , Weisman Paul , Spencer Ryan J. , Kushner David M.
Published: February 2023

BACKGROUND:

Vulvar Paget disease often requires extensive and, in some cases, multiple resections to treat. A fluorescein-mapping procedure followed by a staged vulvectomy may be an effective technique to tailor resection and identify clinically occult lesions.

TECHNIQUE:

We describe a two-step procedure; first, intravenous fluorescein sodium is injected, and the vulva is illuminated with a Wood's lamp. Representative biopsies are obtained and correlated on final pathology with the extent of disease to develop a final plan for excision. Second, using fluorescein to identify the confirmed areas of disease, the appropriate excisional procedure is performed once mapping biopsy pathology is known.

EXPERIENCE:

We describe our experience with eight patients with vulvar Paget disease undergoing fluorescein mapping biopsies and staged vulvectomy. Using intravenous fluorescein sodium, all patients were found to have Paget disease beyond the visible margins of their gross lesions. No patients experienced a recurrence of Paget disease within a median follow-up time of 32 months, comparable with other directed methods of surgical resection.

CONCLUSION:

We report a technique for the injection of fluorescein sodium for the visualization of vulvar Paget disease capable of providing accurate surgical margins and identification of occult satellite lesions with a high degree of safety and a favorable cost profile. This staged approach to vulvectomy could offer improved accuracy of resection for vulvar Paget disease with few drawbacks.
Combination toripalimab and bevacizumab for an elderly urothelial carcinoma patient with brain metastasis who failed rapidly after radiotherapy: a case report and literature review
Authors: Qu Fanjie , Yan Xin , Yu Weiwei
Published: February 2023

Brain metastasis is a rare refractory event in patients with urothelial carcinoma. Platinum-based chemotherapy is the recommended first-line standard therapy for all metastasis urothelial carcinoma patients eligible for cisplatin or carboplatin. Patients ineligible for platinum may receive immunotherapy. No clear evidence exists that UC with brain metastasis is sensitive to immunotherapy, and the optimal treatment for patients with BM is uncertain. We evaluated the safety and efficacy of combined immunotherapy and antivascular therapy in an elderly patient with urothelial carcinoma with brain metastasis, and summarize the currently available evidence. First, she underwent a left nephrectomy and left ureterectomy and recovered well postoperatively. The postoperative pathologic findings were consistent with urothelial carcinoma. Approximately 2 years later, the patient developed impaired limb movement on the right side and underwent MRI, which revealed lesions in the left frontal lobe and suggested brain metastasis. The brain metastasis responded to local radiotherapy but progressed again in a short time. Then, the patient was administered toripalimab at 240 mg combined with bevacizumab at 300 mg every 3 weeks. After 1cycle of treatment, the patient achieved a quick response, and symptoms improved significantly. Repeat evaluation imaging demonstrated that the lesions in the brain and lung were significantly smaller and evaluation showed partial response. The treatment was well tolerated and the patient remained in partial response until the last follow-up by July 2022, 6 months after the initiation of treatment. This case suggests that immune checkpoint blockade combined with antivascular therapy might be a new possibility for patients with metastatic urothelial carcinoma, including brain metastases.
Instruments Assessing Cognitive Impairment in Survivors of Critical Illness and Reporting of Race Norms: A Systematic Review
Authors: Raman Rameela , DesAutels Spencer J. , Lauck Alana M. , Scher Alexa M. , Walden Rachel L. , Kiehl Amy L. , Collar Erin M. , Ely E. Wesley , Pandharipande Pratik P. , Jackson James C.
Published: February 2023

OBJECTIVE:

To conduct a systematic review to summarize cognitive instruments being used in long-term outcome studies of survivors of adult critical illness, as well as evaluate whether these measures are reported as using patient demographic norms, specifically race norms.

DATA SOURCES:

A comprehensive search was conducted in PubMed (National Center for Biotechnology Information), Excerpta Medica dataBASE (Ovid), Psychological Information Database (ProQuest), and Web of Science (Clarivate) for English language studies published since 2002.

STUDY SELECTION:

Studies were eligible if the population included adult ICU survivors assessed for postdischarge cognitive outcomes.

DATA EXTRACTION:

Two independent reviewers screened abstracts, examined full text, and extracted data from all eligible articles.

DATA SYNTHESIS:

A total of 98 articles (55 unique cohorts: 22 general ICU, 14 Acute respiratory distress syndrome/Acute respiratory failure/Sepsis, 19 COVID-19 and other subpopulations) were eligible for data extraction and synthesis. Among general ICU survivors, the majority of studies (n = 15, 68%) assessed cognition using multiple instruments, of which the most common was the Mini-Mental State Examination. Only nine of the 22 studies (41%) explicitly reported using patient demographic norms for scoring neuropsychological cognitive tests. Of the nine, all reported using age as a norming characteristic, education was reported in eight (89%), sex/gender was reported in five (55%), and race/ethnicity was reported in three (33%). Among Acute respiratory distress syndrome/Acute respiratory failure/Sepsis survivors, norming characteristics were reported in only four (28%) of the 14 studies, of which all reported using age and none reported using race/ethnicity.

CONCLUSIONS:

Less than half of the studies measuring cognitive outcomes in ICU survivors reported the use of norming characteristics. There is substantial heterogeneity in how studies reported the use of cognitive instruments, and hence, the prevalence of the use of patient norms may be underestimated. These findings are important in the development of appropriate standards for use and reporting of neuropsychological tests among ICU survivors.
DNA methylation of GITR, OX40, 4-1BB, CD27, and CD40 correlates with BAP1 aberrancy and prognosis in uveal melanoma
Authors: Hoffmann Friederike , Fröhlich Anne , Sirokay Judith , de Vos Luka , Zarbl Romina , Dietrich Jörn , Strieth Sebastian , Landsberg Jennifer , Dietrich Dimo
Published: February 2023

Uveal melanoma represents an aggressive tumor that responds mostly poorly to established melanoma treatments. Comprehensive methylation profiling of the next-generation immunotherapeutic target genes, for example, members of the tumor necrosis factor receptor superfamily, might allow for the development of companion predictive biomarkers. We have analyzed CpG sites within the immune checkpoint genes GITR, OX40, 4-1BB, CD27, and CD40 probed by the Illumina Infinium HumanMethylation450 BeadChip in N = 80 uveal melanomas included in The Cancer Genome Atlas with regard to BAP1 aberrancy, mRNA expression, and overall survival. In all analyzed immune checkpoint genes, BAP1 aberrancy was associated with decreased CpG methylation levels. We identified specific CpG sites that significantly correlated with BAP1 aberrancy, mRNA expression levels, and overall survival. Our results suggest epigenetic regulation of the analyzed immune checkpoint genes via DNA methylation in uveal melanoma and provide rationale for methylation testing in biomarker programs in clinical trials.
Lagged acute respiratory outcomes among children related to ambient pollutant exposure in a high exposure setting in South Africa
Authors: Phaswana Shumani , Wright Caradee Y , Garland Rebecca M , Khumalo Thulie N , Naidoo Rajen N
Published: February 2023

Background:

Acute ambient air pollution impacts on the respiratory health of children may be lagged across time. We determined the short-term lagged effects of particulate matter (PM2.5), sulphur dioxide (SO2), and oxides of nitrogen (NOx) on the respiratory health of children living in low-income communities.

Methods:

A school-based study was conducted using a repeated measures design, across summer and winter, in four schools in each of four suburbs in the Vaal Triangle, South Africa. Data for PM2.5, NOx, and SO2 were obtained from monitoring stations within close proximity of the schools. Over 10 school days in each phase, grade 4 children completed a symptoms log and lung function tests. Parents completed a child respiratory questionnaire. Generalized estimation equations models adjusted for covariates of interest in relation to lung function outcomes and air pollutants including lag effects of 1–5 days.

Results:

Daily PM2.5, NOx, and SO2 median concentration levels were frequently higher than international standards. Among the 280 child participants (mean age 9 years), the prevalence of symptoms based on probable asthma was 9.6%. There was a consistent increased pollutant-related risk for respiratory symptoms, except for NOx and shortness of breath. Lung function, associated with pollutant fluctuations across the different lags, was most pronounced for peak expiratory flow rate (PEFR) for PM2.5 and SO2. A preceding 5-day average SO2 exposure had the largest loss (7.5 L/minute) in PEFR.

Conclusions:

Lagged declines in daily lung function and increased odds of having respiratory symptoms were related to increases in PM2.5 and SO2 among a school-based sample of children.
Ambient exposures to selected volatile organic compounds and the risk of prostate cancer in Montreal
Authors: Goldberg Mark S. , Zapata-Marin Sara , Labrèche France , Ho Vikki , Lavigne Eric , Valois Marie-France , Parent Marie-Elise
Published: February 2023

Background:

Little is known about environmental factors that may increase the risk of prostate cancer. We estimated associations between incident prostate cancer and environmental concentrations of five ambient volatile organic compounds (VOCs): benzene; n-decane; ethylbenzene; hexane; and 1,2,4-trimethylbenzene.

Methods:

This study is based on a population-based case-control study of incident prostate cancer (PROtEuS) in men ≤ 75 years of age living in Montreal, Canada, in 2005 to 2012. We included 1172 cases and 1177 population controls. We had personal information, lifetime residential addresses, occupational exposures, and a variety of area-wide covariables. We inferred concentrations of the five VOCs using Bayesian geostatistical models using data from a dense environmental survey conducted in Montreal in 2005 to 2006. We used different sets of adjustments to estimate odds ratios (OR) and confidence intervals.

Results:

We found nonlinear associations such that the ORs increased monotonically and then either flattened or fell off with increased exposures. The model that contained other environmental variables and contextual variables led to lower ORs and results were similar when we restricted analyses to controls recently screened or tested for prostate cancer or cases with low- or high-grade tumors. A change from the 5th to 25th percentile in mean environmental benzene levels led to an adjusted OR of 2.00 (95% confidence interval = 1.47, 2.71).

Conclusion:

We found positive associations between prostate cancer and concentrations of benzene and ethylbenzene, independently of previous testing for prostate cancer or tumor grade, suggesting that exposure to certain ambient VOCs may increase incidence.
Autologous Minimally Manipulated Homologous Adipose Tissue (AMHAT) for Treatment of Nonhealing Diabetic Foot Ulcers
Authors: Armstrong David G. , Harris Steven G. , Rasor Zachary , Zelen Charles M. , Kim Jeehee , Swerdlow Mark , Isaac Adam L.
Published: February 2023

Background:

Diabetic foot complications are increasingly burdensome for patients, clinicians, and society. Development of innovative therapies to support good quality basic care is a priority among those with an interest in this area. One of these involves scanning and printing tissues to match and conform to a defect (so-called 3D printing).

Methods:

A single-arm pilot study of ten consecutive patients with a history of a chronic diabetic foot ulcer (DFU), treated with autologous minimally manipulated homologous adipose tissue (AMHAT), dispensed by a specialized 3D bioprinter, Dr. INVIVO, was performed. Patients with nonhealing DFUs present for more than 4 weeks and refractory to standard-of-care therapies were included. Wounds were treated with a single application of AMHAT, and then followed up weekly for up to 12 weeks, or until the wounds healed. The primary outcome measure was complete epithelialization of the wound up to 12 weeks after the treatment. Secondary outcome measures included wound size and/or volume reduction, assessment of ulcer grade, and time to closure.

Results:

Five wounds were healed by 5 weeks and one at 8 weeks. The mean percent area reduction at 12 weeks was 78.3% (SD: 33.23). Complete closure was achieved in 60% of wounds. The mean time to closure in these wounds was 49.1 days (95% CI, 29.9–68.3). No adverse events were reported.

Conclusions:

Single treatment of bioprinted AMHAT appears to be a safe and potentially effective treatment modality for patients with chronic DFUs. Further studies are warranted to explore the full potential of 3D bioprinting for tissue repair in this high-risk population.
Lactose Stabilization Prolongs In Vivo Retention of Cross-linked Fish Collagen Subcutaneous Grafts in Nude Mice
Authors: Yamaoka Hisayo , Yamaoka Keiko , Watanabe Shigekazu , Tanaka Hideyuki , Hosoyamada Makoto , Komuro Yuzo
Published: February 2023

Background:

Bovine-derived collagen gel has been used in the medical field as an injection formulation, but there are concerns about cross-infection such as bovine spongiform encephalopathy. In this study, we attempted to use fish as a safe alternative to bovine collagen.

Objective:

Fish collagen has not been used in clinical settings, so we examined its potential by comparing its properties with those of bovine-derived collagen.

Methods:

Collagen was extracted from the ventral skin of flatfish. It was cross-linked with 1%, 3%, or 5% of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC) and treated with 1%, 5%, or 10% of lactose. Hydroxyproline contents and Young’s modulus (elasticity) were measured. In addition, these were injected under the back of BALB/c nude mice and the amount of hydroxyproline was observed. Histological examination of the samples was also conducted.

Results:

The amount of hydroxyproline in fish collagen was 3.3 ± 0.3 μg/mg. The 3% collagen gel treated with 5% EDC and 5% lactose had the highest Young’s modulus and was closest to the bovine-derived collagen injection formulation. When injected into mice, it was retained in vivo for about 90 days.

Conclusions:

Fish collagen has a low denaturation temperature and is unstable and easily biodegrades in mammalian organisms. However, it is possible to approach the properties of conventional mammalian collagen by cross-linking and lactose treatment, suggesting that fish collagen can be used as a scaffold for cells in regenerative medicine.
Full versus Baby Dose Aspirin for Antithrombotic Prophylaxis in Free Tissue Transfer: Does Size Matter?
Authors: Karamanos Efstathios , Hazboun Rajaie , Saad Noah , Bialowas Christie , Wang Howard , Cromack Douglas
Published: February 2023

Background:

The postoperative prophylactic use of aspirin is a common practice among plastic surgeons after free tissue transfer. The use of baby aspirin (81 mg) has become more popular due to previously published literature in other fields. We hypothesized that a full dose daily aspirin is nonsuperior to a baby dose daily aspirin in preventing arterial thrombosis in free tissue transfer.

Methods:

All patients undergoing free tissue transfer of the extremities from 2008 to 2020 were retrospectively reviewed. They were divided into two groups based on the postoperative dose of aspirin administered (full versus baby dose). The decision to administer full or baby dose was based on the surgeon’s preference. Primary outcome was revision of the arterial anastomosis. Secondary outcomes included flap complications.

Results:

A total of 183 patients were identified. Out of those, 78 patients received full dose aspirin postoperatively, whereas 105 received a baby dose of aspirin. Patients who received baby aspirin did not have a higher incidence of returning to the operating room for revision of their arterial anastomosis [7.6% versus 7.7%; adjusted odds ratio, 0.93 (95% confidence interval, 0.28‐3.11); adjusted P, 0.906]. No differences were found between the two groups in complete and partial flap loss, wound dehiscence, or infection. None of the patients experienced any aspirin-related gastrointestinal complications.

Conclusions:

In patients undergoing free tissue transfer, thrombosis of the arterial anastomosis is rare. Administration of a full dose of aspirin postoperatively was not superior to a baby dose of aspirin in preventing arterial-related complications.
Abnormal Platelet Counts and Clonal Hematopoiesis in the General Population
Authors: Kamphuis Priscilla , van Bergen Maaike G.J.M. , van Zeventer Isabelle A. , de Graaf Aniek O. , Dinmohamed Avinash G. , Salzbrunn Jonas B. , Schuringa Jan Jacob , van der Reijden Bert A. , Huls Gerwin , Jansen Joop H.
Published: February 2023

Clonal hematopoiesis (CH) is defined by the presence of somatic mutations that may cause clonal expansion of hematopoietic cells. Here, we investigated the association between platelet count abnormalities, CH and consequences on overall survival and the development of hematological malignancies. Individuals with thrombocytopenia (n = 631) or thrombocytosis (n = 178) ≥60 years, and their age- and sex-matched controls, were selected within the population-based Lifelines cohort (n = 167,729). Although the prevalence of CH was not increased in thrombocytopenia cases compared with their controls (37.9% vs 39.3%; P = 0.639), mutations in spliceosome genes (SF3B1, SRSF2, U2AF1) were significantly enriched in thrombocytopenia cases (P = 0.007). Overall, CH in combination with thrombocytopenia did not impact on survival, but thrombocytopenia in combination with multiple mutated genes (hazard ratio [HR] = 2.08, 95% confidence interval [CI], 1.24-3.50; P = 0.006), mutations in TP53 (HR = 5.83, 95% CI, 2.49-13.64; P < 0.001) or spliceosome genes (HR = 2.69, 95% CI, 1.29-5.63; P = 0.009) increased the risk of death. The prevalence of CH in thrombocytosis cases was higher compared with controls (55.8% vs 37.7%; P < 0.001). Especially mutations in JAK2 (P < 0.001) and CALR (P = 0.003) were enriched in individuals with thrombocytosis. The presence of CH in individuals with thrombocytosis did not impact on overall survival. However, during follow-up of 11 years 23% of the individuals with thrombocytosis and CH were diagnosed with hematological malignancies. From these, 81% were diagnosed with myeloproliferative disease and 76% carried driver mutations JAK2, CALR, or MPL.
NORMAL PERIPHERAL CHOROIDAL THICKNESS MEASURED BY WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY
Authors: Funatsu Ryoh , Sonoda Shozo , Terasaki Hiroto , Shiihara Hideki , Mihara Naohisa , Horie Juun , Sakamoto Taiji
Published: February 2023

Purpose:

Choroidal stasis plays an important role in the pathogenesis of many conditions and leads to choroidal thickening. However, the normal peripheral choroidal thickness (PCT) pattern remains unknown. This study investigated PCT and associated factors using ultrawidefield optical coherence tomography in healthy eyes.

Methods:

This cross-sectional study included 120 healthy eyes (57 males; age, 52.0 ± 20.5 years). We used choroidal thickness maps created by ultrawidefield optical coherence tomography (viewing angle, 200°) with real-shape correction. The peripheral area was defined from 60° to 100° and further separated vertically and horizontally. The PCT and the correlations between PCT and subjects' characteristics were examined.

Results:

The PCT were 227.1 ± 57.0 µm, 199.6 ± 53.9 µm, 196.6 ± 57.1 µm, and 148.0 ± 38.2 µm in supratemporal, infratemporal, supranasal, and infranasal areas, respectively. The thickest peripheral sector was most frequently observed in supratemporal (69.2%). The PCT negatively correlated with age in all regions (P-values < 0.001) and axial length in supratemporal, supranasal, and infranasal areas (P-values ≤ 0.003). The temporal PCT was thicker on the side contiguous with the posterior pole Haller's vessels (P-values ≤ 0.020).

Conclusion:

The PCT is associated with age, axial length, and the running pattern of Haller's vessels.