bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary antitumor activity of the combination of COM701 + BMS-986207 + nivolumab in patients with recurrent, metastatic MSS endometrial cancer.
Authors: Rasco Drew W. , Vaena Daniel A. , Fleming Gini F. , Dumbrava Ecaterina Elena , Yeku Oladapo O. , Sharma Manish , Papadopoulos Kyriakos P. , Sullivan Ryan J. , Gaillard Stephanie , Adewoye Adeboye H. , Moroney John William 
Published: June 2023

5595 Background: There is a high unmet medical need for the treatment of patients [pts] with microsatellite stable [MSS], recurrent, metastatic, endometrial cancer [EC]. We reported encouraging preliminary antitumor activity with the triple combination of COM701 + BMS-986207 + nivolumab in patients with platinum resistant epithelial ovarian cancer [1]. COM701 is a novel, 1st-in-class immune checkpoint inhibitor [ICI] that binds to PVRIG, a DNAM-1 axis member, leading to activation of T-and NK-cells; BMS-986207 is an ICI of TIGIT. Nivolumab is an ICI of PD-1. We hypothesized that in pts with EC, the triple combination would demonstrate antitumor activity with a favorable safety and tolerability profile. We present encouraging preliminary results. Methods: As part of an expansion cohort, we enrolled 9 patients [pts] with EC. All pts received COM701 20 mg/kg + BMS-986207 480 mg + nivolumab 480 mg all IV Q4W. Primary objectives were safety/tolerability, with secondary objective of antitumor activity in pts with EC. Key inclusion criteria: Age ≥ 18 yrs, measurable disease, MSS by IHC or genomic testing, ≤2 prior systemic cytotoxic therapies, prior PD-1/PD-L1 permissible. Key exclusion criteria: prior receipt of anti-PVRIG, anti-TIGIT. Investigator assessed responses were per RECIST v1.1, safety per CTCAE v5.0. Results: Median age 71yrs, median of 2 prior lines of therapy, prior PD-1/PD-L1 3/9 [33%]. All pts received prior cytotoxic therapy. Objective response rate (ORR) 2/9 [22%] pts; 2 pts with SD. Disease control rate [CR + PR + SD] 4/9 [44%]. There were 2 pts with confirmed PR; 1 of these pts was refractory to prior receipt of lenvatinib + pembrolizumab [best response assessment of progressive disease]. Treatment related AEs were reported in 6/9 [67%] pts, the majority 4/6 [67%] were Grade 1 [1 pt each with chills, pyrexia, back pain and pruritus, lipase increased]. No new safety signals are reported. Conclusions: The combination of COM701 + BMS-986207 + nivolumab demonstrates encouraging preliminary signal of antitumor activity in pts with EC including in a pt refractory to prior exposure to lenvatinib + pembrolizumab. The triplet combination has a favorable safety/tolerability profile. Additional data analyses and pt follow up are ongoing and will be presented at the conference. Data extract 01/24/2023. 1. Moroney JW, Yeku O et al. Triple blockade of the DNAM-axis with COM701 + BMS-986207 + nivolumab demonstrates preliminary antitumor activity in patients with platinum resistant OVCA. Annals of Oncology (2022) 16 (suppl_1): 100104-100104. 10.1016/iotech/iotech100104. Clinical trial information: NCT04570839 .
Seven-Year Follow-Up of the Phase III KEYNOTE-006 Study: Pembrolizumab Versus Ipilimumab in Advanced Melanoma
Authors: Robert Caroline , Carlino Matteo S. , McNeil Catriona , Ribas Antoni , Grob Jean-Jacques , Schachter Jacob , Nyakas Marta , Kee Damien , Petrella Teresa M. , Blaustein Arnold , Lotem Michal , Arance Ana , Daud Adil I. , Hamid Omid , Larkin James , Anderson James , Krepler Clemens , Grebennik Dmitri , Long Georgina V. 
Published: June 2023

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. Immune checkpoint inhibitors have led to unprecedented prolongation of overall survival (OS) for patients with advanced melanoma. Five-year follow-up of KEYNOTE-006 showed pembrolizumab prolonged survival versus ipilimumab. Efficacy results with 7-year follow-up are presented. At data cutoff (April 19, 2021), median follow-up was 85.3 months (range, 0.03-90.8 months). Median OS was 32.7 months for pembrolizumab versus 15.9 months for ipilimumab (hazard ratio [HR], 0.70; 95% CI, 0.58 to 0.83); 7-year OS was 37.8% and 25.3%, respectively. OS HRs favored pembrolizumab regardless of BRAF status or prior BRAF/MEK-inhibitor treatment and prognostic characteristics (elevated lactate dehydrogenase, large tumor size, and brain metastasis). Median modified progression-free survival (mPFS) was 9.4 months for pembrolizumab versus 3.8 months for ipilimumab; 7-year mPFS was 23.8% and 13.3%, respectively. In patients who completed ≥94 weeks of pembrolizumab, the 5-year OS was 92.9% and the 5-year mPFS was 70.1%. The objective response rate with second-course pembrolizumab (n = 16) was 56% (95% CI, 30 to 80) and the 2-year mPFS was 62.5%. These findings confirm that pembrolizumab provides long-term survival benefit in advanced melanoma.
Those Were the Days and Then
Authors: Clough Patricia Ticineto 
Published: June 2023

Abstract
Remembering Stanley Aronowitz brings the author to reflect on the intersection of the personal and the political in academic departments and academic friendships. This intersection can become difficult, especially when colleagues are on the margins, politically and pedagogically, of a department and a discipline. The result can be the rupturing of friendships and the weakening of political alliances that had supported a critical stance toward the discipline and the department.
Natural antisense transcription of presenilin in sea urchin reveals a possible role for natural antisense transcription in the general control of gene expression during development
Authors: Bronchain Odile , Ducos Bertrand , Putzer Harald , Delagrange Marine , Laalami Soumaya , Philippe-Caraty Laetitia , Saroul Krystel , Ciapa Brigitte 
Published: June 2023

ABSTRACT
One presenilin gene (PSEN) is expressed in the sea urchin embryo, in the vegetal pole of the gastrula and then mainly in cilia cells located around the digestive system of the pluteus, as we recently have reported. PSEN expression must be accurately regulated for correct execution of these two steps of development. While investigating PSEN expression changes in embryos after expansion of endoderm with LiCl or of ectoderm with Zn2+ by whole-mount in situ hybridization (WISH) and quantitative PCR (qPCR), we detected natural antisense transcription of PSEN. We then found that Endo16 and Wnt5, markers of endo-mesoderm, and of Hnf6 and Gsc, markers of ectoderm, are also sense and antisense transcribed. We discuss that general gene expression could depend on both sense and antisense transcription. This mechanism, together with the PSEN gene, should be included in gene regulatory networks (GRNs) that theorize diverse processes in this species. We suggest that it would also be relevant to investigate natural antisense transcription of PSEN in the field of Alzheimer's disease (AD) where the role of human PSEN1 and PSEN2 is well known.
Dynamics and energetics of bottlenose dolphin (Tursiops truncatus) fluke-and-glide gait
Authors: Zhang Ding , Wang Yifan , Gabaldon Joaquin , Lauderdale Lisa K. , Miller Lance J. , Barton Kira , Shorter Kenneth Alex 
Published: June 2023

ABSTRACT
Intermittent locomotion composed of periods of active flapping/stroking followed by inactive gliding has been observed with species that inhabit both aerial and marine environments. However, studies on the energetic benefits of a fluke-and-glide (FG) gait during horizontal locomotion are limited for dolphins. This work presents a physics-based model of FG gait and an analysis of the associated cost of transport for bottlenose dolphins (Tursiops truncatus). New gliding drag coefficients for the model were estimated using measured data from free-swimming bottlenose dolphins. The data-driven approach used kinematic measurement from 84 h of biologging tag data collected from three animals to estimate the coefficients. A set of 532 qualifying gliding events were automatically extracted for estimation of the gliding drag coefficient. Next, data from 783 FG bouts were parameterized and used with the model-based dynamic analysis to investigate the cost benefits of FG gait. Experimental results indicate that FG gait was preferred at speeds of ∼2.2–2.7 m s−1. Observed FG bouts had an average duty factor of 0.45 and a gliding duration of 5 s. The average associated metabolic cost of transport (COT) and mechanical cost of transport (MECOT) of FG gait are 2.53 and 0.35 J m−1 kg−1, respectively, at the preferred speeds. This corresponded to a respective 18.9% and 27.1% reduction in cost when compared with model predictions of continuous fluking gait at the same average bout speed. Average thrust was positively correlated with fluking frequency and amplitude as animals accelerated during the FG bouts, whereas fluking frequency and amplitude were negatively correlated for a given thrust range. These results suggest that FG gait enhances the horizontal swimming efficiency of bottlenose dolphins and provides new insights into the gait dynamics of these animals.
Deep dives and high tissue density increase mean dive costs in California sea lions (Zalophus californianus)
Authors: Cole Mason R. , Ware Colin , McHuron Elizabeth A. , Costa Daniel P. , Ponganis Paul J. , McDonald Birgitte I. 
Published: June 2023

ABSTRACT
Diving is central to the foraging strategies of many marine mammals and seabirds. Still, the effect of dive depth on foraging cost remains elusive because energy expenditure is difficult to measure at fine temporal scales in wild animals. We used depth and acceleration data from eight lactating California sea lions (Zalophus californianus) to model body density and investigate the effect of dive depth and tissue density on rates of energy expenditure. We calculated body density in 5 s intervals from the rate of gliding descent. We modeled body density across depth in each dive, revealing high tissue densities and diving lung volumes (DLVs). DLV increased with dive depth in four individuals. We used the buoyancy calculated from dive-specific body-density models and drag calculated from swim speed to estimate metabolic power and cost of transport in 5 s intervals during descents and ascents. Deeper dives required greater mean power for round-trip vertical transit, especially in individuals with higher tissue density. These trends likely follow from increased mean swim speed and buoyant hinderance that increasingly outweighs buoyant aid in deeper dives. This suggests that deep diving is either a ‘high-cost, high-reward’ strategy or an energetically expensive option to access prey when prey in shallow waters are limited, and that poor body condition may increase the energetic costs of deep diving. These results add to our mechanistic understanding of how foraging strategy and body condition affect energy expenditure in wild breath-hold divers.
Comparative evaluation of the effects of lighting conditions on the shade selection of maxillary central incisor using visual methods
Authors: Kawade Rewa , Sathe Seema , Apte Aditee 
Published: June 2023

Background: The selection of shade of a tooth is a routine practice for a dentist, especially a prosthodontist, to make esthetically pleasing prostheses. The phenomenon of colour is a matter of perception by the eye. Every opaque object receives light, absorbs some of it and reflects the rest. A tooth being an opaque object, reflects some amount of light. The dominant wavelength of this reflected light is discerned by us as the colour of the tooth. Light has variable properties that influence our perception. Daylight is regarded as the standard source for the selection of the colour of a tooth. Conversely, the lack of optimal circumstances during different times of the day necessitates using artificial illuminants to select shade of a tooth. This study was carried out to compare the accuracy of a shade-matching light (SMILE LINE) to that of standard daylight. Methods: This study followed the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for cross-sectional studies. The study comprised 125 participants of ages ranging from 20 to 30 years. Five observers from the Department of Prosthodontics, Sharad Pawar Dental College (SPDC), Wardha selected the shade of the maxillary central incisor of 125 subjects under sunlight, dental operatory light, and shade-matching light. The statistical analysis was performed using the SPSS software, and Kappa statistics were used to compare the shades selected by the shade-matching light and dental operatory light with sunlight. Results: A strong correlation was discovered between the shades of tooth selected under the shade matching light and shades selected under sunlight for four out of five observers. Conclusions: The shade correcting device gives shades comparable to those selected under sunlight in ideal conditions making it useful as an alternative to sunlight for shade selection.
Outbreaks of COVID-19 in a tuberculosis treatment sanatorium on the Thailand-Myanmar border: a retrospective cohort analysis
Authors: Aung Htet Ko Ko , Swe Lei Lei , Saito Makoto , Lesseps Sophie , Janurian Naw , Tun Win Pa Pa , Maung Maung Banyar , Than Aung , Watthanaworawit Wanitda , Kaewphanderm Napaporn , Gornsawun Gornpan , Pyae Phyo Aung , Nosten François 
Published: June 2023

Background: Tuberculosis (TB) is a chronic condition, with overlapping symptoms to those of coronavirus disease 2019 (COVID-19). There has been inconsistent evidence on whether TB is a predisposing factor for developing severe COVID-19. The aim of this report is to explore whether TB influences the severity of COVID-19. Methods: COVID-19 cases at two TB sanatoria on the Thailand-Myanmar border were reviewed. Demographic, clinical and laboratory data including TB treatment and co-morbidities, were analyzed. Characteristics and COVID-19 clinical outcomes were compared between two groups of patients: TB and those without TB (the caretakers and the medical personnel). Multivariable ordered logistic regression was conducted to compare the risk of severe COVID-19 between the two groups. Results: Between September 2021 and March 2022, 161 COVID-19 cases were diagnosed. Over half of the COVID-19 patients were infected with TB (n= 104, 64.6%), and the rest were not (n=57, 35.4%). The median (interquartile range) age was 48 (33.5-57.0) and 27 (23-33) years in the TB and in the non-TB COVID-19 patients, respectively. Before COVID-19 infection, 78.7% (122/155) of patients had received at least one dose of COVID-19 vaccine. The median cycle threshold value at diagnosis was not different between TB (18.5, IQR 16.1-32.3) and non-TB patients (18.8, 15.1-30.0). Fever, gastrointestinal symptoms and ageusia were more common in non-TB patients. Six patients (3.8%, 6/156) all from the TB group became severe of which five (3.2%, 5/156) required oxygen therapy. One TB patient died (1/104, 0.96%) of lung cancer. After adjustment for potential confounders, the final clinical severity was not different between the two groups (adjusted odds ratio 1.21, 95% confidence interval 0.45–3.28). Conclusions: TB was not associated with severe outcomes in the two TB sanatoria. The high uptake of COVID-19 vaccination and active screening could have impacted on disease progression and prevented unfavorable outcomes.
Post-traumatic stress and awareness in patient with traumatic lower limb surgery by neuraxial anesthesia: A randomized clinical trial
Authors: Hashemian Morteza , Zandrahimi Farshad , Mirafzal Amirhossein , Pakmanesh Hamid , Amirkhosravi Ladan 
Published: June 2023

Aim of the studyAnesthesia decreases brain cognitive function, memory and pain, and also leads to the loss of consciousness. In this study, midazolam and propofol-sedated trauma patients undergoing lower limb surgery were evaluated for stress levels after neuraxial anesthesia.Subject or material and methodsThis double-blind randomized clinical trial was conducted on patients with lower extremity fractures due to trauma, who were candidates of elective lower extremity orthopedic surgery. Patients were randomly divided into two groups of propofol-sedated patients (n=110) and midazolam-sedated patients (n=110) after neuraxial anesthesia. Then, all patients underwent spinal anesthesia using 3 ml of 0.5% bupivacaine (3 mg/kg). Propofol (25-75 µg/kg/minute) was infused, and 1-2 mg of midazolam was injected PRN until patients reached the score of 3 on the Modified Observers' Assessment of Alertness/ Sedation Scale (MOAA/S).ResultsPreoperative sedation/alertness scores of patients in the two groups did not differ significantly from one another. Penetrating memories in the midazolam group was higher than the propofol group (P<0.05). Personal relationship problem was more significant in the midazolam group than the propofol group (P<0.05). Inability in controlling emotional feelings was higher in the midazolam group compared to the propofol group (P<0.001).DiscussionOur findings indicated that a sub-hypnotic dose of propofol provided superior sedation and amnesia compared to midazolam. Aspects of stress, including penetrating memories, personal relationship problems, inability to control emotional feelings, and lack of depression during spinal anesthesia were better managed by propofol compared to midazolam.ConclusionsPropofol infusion was better in decreasing stress levels after surgery compared to midazolam.
A Decision Framework for Evaluating the Rocky Mountain Area Wildfire Dispatching System in Colorado
Authors: Belval Erin J. , Thompson Matthew P. 
Published: June 2023

In recent years, the state of Colorado has experienced extreme wildfire events that have degraded forest and watershed health and devastated human communities. With expanding human development and a changing climate, wildfire activity is likely to increase, and wildfire management agencies will be challenged to sustain landscapes and the ecosystem services they provide. A critical element of the United States’ federal-, state-, and local-level multiagency wildfire response is the interagency dispatching system, which facilitates the ordering, mobilization, and tracking of firefighting resources to and from wildfire incidents—a role that is likely to increase in both importance and workload in the future. Given increasing demands, it is worth considering ways to improve efficiencies, capacity, and capability within the current Colorado dispatching system. With this, the Rocky Mountain Coordinating Group (RMCG) and the Rocky Mountain Area Fire Executive Council (RMA-FEC) sought to reorganize the dispatching system, beginning with exploration of changes to dispatching zone boundaries and the number and location of dispatching centers throughout the state. Here we describe a multiyear research–management partnership with the RMCG and RMA-FEC to apply a structured decision-making process to guide this reorganization effort. We highlight the steps used in a participatory process that involved local decision makers and included iteratively revising and clarifying the problem statement, developing objectives and translating them into measurable attributes, building a multiobjective optimization model to generate and compare alternatives, and communicating a recommended alternative that was ultimately adopted. To conclude, we discuss insights from our experience and highlight opportunities for similar work to support efficient wildfire management elsewhere in the United States. History: This paper has been accepted for the Decision Analysis Special Issue on Decision Analysis to Advance Environmental Sustainability. Funding: This research was supported by the U.S. Department of Agriculture Forest Service.
Common Institutional Ownership and Product Market Threats
Authors: Kini Omesh , Lee Sangho , Shen Mo 
Published: June 2023

The common ownership of firms can have anticompetitive effects by incentivizing collusive outcomes that maximize joint surpluses of the commonly held firms or procompetitive effects through enhanced knowledge spillovers. Using a difference-in-differences regression methodology that exploits mergers between financial institutions as exogenous shocks to common ownership, our baseline results suggest that higher common ownership leads to greater product market fluidity (a text-based metric of competition) and generally leads to more product development and higher investments. These findings suggest that, on average, common ownership spurs dynamism in product spaces rather than tacit collusion between cross-held competitors. This is especially true in economic environments in which it is easier to take advantage of knowledge spillovers. However, common ownership can also inhibit product market competition and dynamism, especially in industries more prone to quasi-monopoly outcomes in product spaces. Implementing a one-size-fits-all regulatory policy limiting common ownership may be harmful in industries with strong spillover opportunities. This paper was accepted by Victoria Ivashina, finance. Supplemental Material: The online appendix and data are available at https://doi.org/10.1287/mnsc.2023.4830 .
Patient experiences of people with leg ulcers during the COVID-19 pandemic
Authors: Cipolletta Sabrina , Amato Guglielmo 
Published: June 2023

Background: The COVID-19 pandemic affected the care of people with chronic leg ulcers (CLUs). Aims: To understand how people with CLUs perceived illness, health care and the public health emergency during the second wave of the COVID-19 pandemic. Methods: Twenty people attending a wound care clinic in Northern Italy participated in semi-structured interviews and a thematic analysis was conducted using the software Atlas.ti 9. Findings: Results show that most of the participants evaluated their healthcare experience as positive but differed in their perceptions of the changes brought about by the pandemic according to their varied illness experiences and perceived social support. Participants were grouped in four trajectories that provided insight into the construction of personalised support strategies for people with CLUs. Conclusion: These results may help inform healthcare interventions and policies in the care of long-term conditions such as CLUs during a widespread emergency in future.