bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase Ib/II Study of Lenvatinib and Pembrolizumab in Advanced Endometrial Carcinoma (Study 111/KEYNOTE-146): Long-Term Efficacy and Safety Update
Authors: Makker Vicky , Aghajanian Carol , Cohn Allen L. , Romeo Margarita , Bratos Raquel , Brose Marcia S. , Messing Mark , Dutta Lea , Dutcus Corina E. , Huang Jie , Schmidt Emmett V. , Orlowski Robert , Taylor Matthew H. 
Published: January 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. The open-label phase Ib/II Study 111/KEYNOTE-146 of daily lenvatinib 20 mg plus pembrolizumab 200 mg once every 3 weeks showed promising efficacy and tolerable safety in patients with previously treated advanced endometrial carcinoma (EC; primary data cutoff date: January 10, 2019). This updated analysis reports long-term follow-up efficacy and safety data from 108 patients with previously treated EC included in the primary analysis. End points included objective response rate, duration of response, progression-free survival, overall survival, and safety. Investigators performed tumor assessments per immune-related RECIST. At the updated data cutoff date (August 18, 2020), the median study follow-up duration was 34.7 months (95% CI, 30.9 to 41.2), the objective response rate was 39.8% (95% CI, 30.5 to 49.7), and the median duration of response was 22.9 months (95% CI, 10.2 to not estimable). The median progression-free survival and overall survival were 7.4 months (95% CI, 5.2 to 8.7) and 17.7 months (95% CI, 15.5 to 25.8), respectively. Treatment-related treatment-emergent adverse events of any grade occurred in 104 (96.3%) patients. The most common grade ≥ 3 treatment-related treatment-emergent adverse events were hypertension (33.3%), elevated lipase (9.3%), fatigue (8.3%), and diarrhea (7.4%). The results demonstrate extended efficacy and tolerability of lenvatinib plus pembrolizumab in this cohort of patients with previously treated advanced EC.
Patient-Reported Symptom Burden and Supportive Care Needs of Patients With Stage II-III Colorectal Cancer During and After Adjuvant Systemic Treatment: A Real-World Evidence Study
Authors: Cuthbert Colleen A. , O'Sullivan Dylan E. , Boyne Devon J. , Brenner Darren R. , Cheung Winson Y. 
Published: January 2023

PURPOSE: Patients with colorectal cancer (CRC) experience a range of physical and psychologic symptoms, and supportive care needs throughout the illness trajectory. We used patient-reported outcomes and administrative health data to describe symptom burden and supportive care needs during and after adjuvant treatment and determine factors associated with changes to symptom burden. METHODS: A retrospective population-based cohort study of patients who were newly diagnosed with stage II-III CRC in Alberta, Canada, between January 1, 2016, and January 31, 2019. Adults age 18 years or older who completed a patient-reported outcomes survey (Edmonton Symptom Assessment System) and supportive care needs (Canadian Problem Checklist) within 3 months after starting adjuvant treatment (during treatment) and > 7 months after starting treatment (after treatment) were included. Changes to symptom severity were stratified as stable, improved, or deteriorated. Multivariable logistic regression was used to evaluate factors associated with these changes. RESULTS: We included 303 patients (median age 60 years, 62% male, 84.5% stage III, 51.2% rectal v colon). Prevalent symptoms included tiredness (80.5%), pain (50.8%), and poor well-being (50%) during treatment, and tiredness (71.3%), pain (44.2%), and poor well-being (62.1%) after treatment. The results were heterogeneous with respect to improvements, stability, or deterioration. Pain worsened for 25% of the cohort, tiredness for 28%, and depression, anxiety, and well-being for 21%, 22%, and 31%, respectively. Deterioration of some symptoms was associated with older age, stage II, comorbidities, rural setting, and higher income. CONCLUSION: We demonstrated symptom severity was generally low and most symptoms remained stable or improved after treatment. Particular groups of patients were at greater risk for more severe and/or more persistent symptoms. Ongoing assessments and interventions to address physical and psychologic symptoms, and supportive care needs in patients with CRC during and after treatment are needed.
The AKT1-FOXO4 axis reciprocally regulates hemochorial placentation
Authors: Kozai Keisuke , Moreno-Irusta Ayelen , Iqbal Khursheed , Winchester Mae-Lan , Scott Regan L. , Simon Mikaela E. , Muto Masanaga , Parrish Marc R. , Soares Michael J. 
Published: January 2023

ABSTRACT
Hemochorial placentation involves the differentiation of invasive trophoblast cells, specialized cells that possess the capacity to exit the placenta and invade into the uterus where they restructure the vasculature. Invasive trophoblast cells arise from a well-defined compartment within the placenta, referred to as the junctional zone in rat and the extravillous trophoblast cell column in human. In this study, we investigated roles for AKT1, a serine/threonine kinase, in placental development using a genome-edited/loss-of-function rat model. Disruption of AKT1 resulted in placental, fetal and postnatal growth restriction. Forkhead box O4 (Foxo4), which encodes a transcription factor and known AKT substrate, was abundantly expressed in the junctional zone and in invasive trophoblast cells of the rat placentation site. Foxo4 gene disruption using genome editing resulted in placentomegaly, including an enlarged junctional zone. AKT1 and FOXO4 regulate the expression of many of the same transcripts expressed by trophoblast cells, but in opposite directions. In summary, we have identified AKT1 and FOXO4 as part of a regulatory network that reciprocally controls critical indices of hemochorial placenta development.
TMJ Disorders in Athletes
Authors: Starr Carter L. , McGrew Christopher 
Published: January 2023

Abstract
Temporomandibular joint dysfunction is common in both the general population and athletes with a much higher incidence in women than in men. We review current research on temporomandibular joint disorders, discuss relevant risk factors, manifestations of temporomandibular disorders in athletes, and treatment options. Certain sports, particularly contact sports, pose an increased risk for problems with the temporomandibular joint. The stress of athletic performance also may be a contributing factor. Mouthguards should be encouraged for prevention of injury and physical therapy is the most effective treatment.
The Mode of Endurance Exercise Influences Changes in EEG Resting-State Graphs among High-Level Cross-Country Skiers
Authors: BÜCHEL DANIEL , TORVIK PER ØYVIND , LEHMANN TIM , SANDBAKK ØYVIND , BAUMEISTER JOCHEN 
Published: January 2023

ABSTRACT

Purpose
Acute bouts of exercise influence the communication and organization of brain networks, with exercise intensity and volume regarded as key moderators. However, differences in coordination demands and limb involvement between exercise modes may also affect the communication and organization of brain networks after exercise and should be considered additionally. This study aimed to investigate the effect of mode on exercise-induced changes in electroencephalogaphy (EEG) resting-state networks comparing running (RUN) and cross-country skating (XC).

Methods
Fifteen male, highly trained participants were tested for peak oxygen uptake (V̇O2peak) during RUN (65.3 mL·min−1·kg−1) and XC (63.5 mL·min−1·kg−1) followed by incremental protocols at 50%, 70%, and 90% of speed at V̇O2peak in both modes on the treadmill. After each exercise bout, 5-min resting-state EEG assessments using 64 channels were performed. Upon graph theory, small world index (SWI), clustering coefficient (CC), and path length (PL) were assessed in theta, alpha-1 and alpha-2 frequency bands. Repeated-measures ANOVA was applied to analyze the influence of exercise intensity and mode on modulations in brain network efficiency.

Results
Main effects of mode on SWI (P = 0.047), CC (P < 0.001), and PL (P = 0.031) in the alpha-2 network indicated stronger modulations in network efficiency after XC. Main effects of exercise intensity in the theta network indicated modulated SWI (P < 0.001), CC (P < 0.001), and PL (P = 0.003) after exercise at 90% of V̇O2peak speed. Physiological outcomes (heart rate, blood lactate concentration, and rating of perceived exertion) were influenced by intensity solely.

Conclusions
The present study demonstrates that an acute bout of coordinatively challenging endurance exercise may affect brain networks differently compared with running. Future studies may consider exercise mode as a potential moderator in the acute interaction between exercise and the brain.
Diagnostic accuracy of magnetic resonance imaging to evaluate axillary lymph node status in breast cancer patients receiving neoadjuvant chemotherapy
Authors: Bansal Gaurav Jyoti , Jaipal Amarta , Wu Genie K C , Syed Ayesha 
Published: January 2023

Objectives: Axillary lymph node status is an important prognostic factor for breast cancer patients. This study aimed to assess the accuracy of MRI in assessing the axillary nodal status in breast cancer patients receiving neo-adjuvant chemotherapy (NACT). Methods: Data were retrospectively collected for 88 patients between 2011 and 2016 from the hospital records. All patients had baseline MRI, followed by the end of neoadjuvant chemotherapy MRI. Patient demographics, cancer type, grade, stage, receptor status, and the number of positive lymph nodes identified on the baseline and preoperative MRI were recorded. The imaging results were compared to post-operative histopathological lymph node findings. The median patient age of the patients was 54 years (32–77 years) Results: There were 67 (76.1%) patients with histologically proven positive axillary lymph nodes on baseline MRI. The overall conversion from abnormal to normal axillary nodes following chemotherapy (ypN0) was 38.8% (26 patients out of 67). The sensitivity and specificity of MRI for predicting axillary status was 68.85 and 85.71%, respectively, with an overall MRI diagnostic accuracy of 73.07%. Conclusion: MRI has low sensitivity and diagnostic accuracy in predicting axillary nodal status in breast cancer patients receiving neoadjuvant chemotherapy. Given the low NPV of MRI of the axilla, a negative MRI does not obviate the need for definitive axillary surgery. Advances in knowledge: In its current state, MRI cannot obviate the need for axillary surgery in patients receiving NACT. Long: short axis ratio (L: S) of the axillary lymph node is not a good predictor of axillary metastases.
Pharmacy students' empathy and its determinants: a systematic review
Authors: Pratiwi Hening , Ari Kristina Susi , Wahyuni Widayanti Anna , Suryo Prabandari Yayi 
Published: January 2023

Background: Empathy in the context of healthcare is an immersion experience to comprehend patients' viewpoints, feelings, and emotions, without passing judgment, to ensure they receive the necessary treatment to feel comfortable. Empathy for others must be possessed by healthcare professionals and healthcare students as healthcare professionals’ candidates, including the pharmacy student. This study aimed to identify and assess the determinants related to pharmacy students' empathy. Methods: Three electronic databases were used for the first searches. We used peer-reviewed original papers, full text, must assess determinants that are associated with pharmacy students' empathy, and only be focused on pharmacy students (first to the fourth year) as healthcare professionals candidates. We utilized Joanna Briggs Institute Critical Appraisal Checklists to observe the quality of published publications and reduce bias. Results: This review examined 14 papers that reported on determinants connected to pharmacy students' empathy. Nine studies evaluated the association between sex and the level of empathy, seven studies reported educational intervention, four studies discussed the year of study, two studies explained the type of school, four studies evaluated experience, and others determinants that discussed in the included studies were career preference, intercultural sensitivity, stigma, altruism, grit, self-awareness, marital status, and family income Conclusions: Educational intervention, experience, gender or sex, type of school, year of study, intercultural sensitivity, career preference, altruism, grit, self-awareness, marital status, and family income, can all have a positive impact on increased empathy among pharmacy students. We acknowledge that the included studies are heterogeneous, indicating that additional studies are necessary before reaching any firm conclusions. More research is needed to properly understand how empathy can be improved with the most effective pharmacy educational strategies. Higher levels of evidence are also required in studies to address the potential bias caused using self-report questionnaires, as well as other potential biases and inaccuracies.
3D-printing of porous structures for reproduction of a femoral bone
Authors: Alessandri Giulia , Santi Gian Maria , Martelli Paolo , Guidotti Eleonora , Liverani Alfredo 
Published: January 2023

Background: 3D-printing has shown potential in several medical advances because of its ability to create patient-specific surgical models and instruments. In fact, this technology makes it possible to acquire and study physical models that accurately reproduce patient-specific anatomy. The challenge is to apply 3D-printing to reproduce the porous structure of a bone tissue, consisting of compact bone, spongy bone and bone marrow. Methods: An interesting approach is presented here for reproducing the structure of a bone tissue of a femur by 3D-printing porous structure. Through the process of CT segmentation, the distribution of bone density was analysed. In 3D-printing, the bone density was compared with the density of infill. Results: The zone of compact bone, the zone of spongy bone and the zone of bone marrow can be recognized in the 3D printed model by a porous density additive manufacturing method. Conclusions: The application of 3D-printing to reproduce a porous structure, such as that of a bone, makes it possible to obtain physical anatomical models that likely represent the internal structure of a bone tissue. This process is low cost and easily reproduced.
Experiences of the International In-Training Examination (I-ITE) by Rwandan pediatric residents – a survey-study describing candidate feedback
Authors: Cartledge Peter Thomas , Umuhoza Christian , McCall Natalie 
Published: January 2023

Background: The University of Rwanda is the only African residency to have implemented the pediatric International In-Training Examination (I-ITE) as a tool to monitor resident knowledge acquisition. The objective of this study was to better understand the acceptance and relevance of this exam to residents from this setting and their perceptions regarding this assessment tool. Methods: A retrospective, survey-study was undertaken to describe candidate feedback. Immediately on completing the I-ITE residents provided feedback by filling in an electronic questionnaire comprised of four closed Likert questions and an open text box for free-text feedback. Participants were pediatric residents from the University of Rwanda, the only university in Rwanda with a pediatric residency program. Quantitative analysis of the Likert questions was undertaken descriptively using SPSS. Free-text feedback was coded and analysed employing a phenomenological approach, with coding and analysis undertaken by two researchers. Results: Eighty-four residents completed a total of 213 I-ITE sittings during the five exam cycles undertaken during the study period. The survey was completed after 206 of the 213 exam sittings, giving a response rate of 97%. Five themes emerged from the qualitative analysis; 1) undertaking the I-ITE was a positive experience; 2) exam content; 3) formative nature of the assessment; 4) challenges to completing the exam; 5) practicalities to undertaking the exam. Conclusion: Qualitative feedback demonstrates that the I-ITE, a standardized, and independent exam, produced by the American Board of Pediatrics, was valued and well accepted by Rwanda pediatric residents. Its formative nature and the breadth and quality of the questions were reported to positively contribute to the residents' formative development.
Environmental surveillance for Salmonella Typhi as a tool to estimate the incidence of typhoid fever in low-income populations.
Authors: Uzzell Christopher B. , Troman Catherine M. , Rigby Jonathan , Raghava Mohan Venkata , John Jacob , Abraham Dilip , Srinivasan Rajan , Nair Satheesh , Meschke John Scott , Elviss Nicola , Kang Gagandeep , Feasey Nicholas A. , Grassly Nicholas C. 
Published: January 2023

Background: The World Health Organisation recommends prioritised use of recently prequalified typhoid conjugate vaccines in countries with the highest incidence of typhoid fever. However, representative typhoid surveillance data are lacking in many low-income countries because of the costs and challenges of diagnostic clinical microbiology. Environmental surveillance (ES) of Salmonella Typhi in sewage and wastewater using molecular methods may offer a low-cost alternative, but its performance in comparison with clinical surveillance has not been assessed. Methods: We developed a harmonised protocol for typhoid ES and its implementation in communities in India and Malawi where it will be compared with findings from hospital-based surveillance for typhoid fever. The protocol includes methods for ES site selection based on geospatial analysis, grab and trap sample collection at sewage and wastewater sites, and laboratory methods for sample processing, concentration and quantitative polymerase chain reaction (PCR) to detect Salmonella Typhi. The optimal locations for ES sites based on digital elevation models and mapping of sewage and river networks are described for each community and their suitability confirmed through field investigation. We will compare the prevalence and abundance of Salmonella Typhi in ES samples collected each month over a 12-month period to the incidence of blood culture confirmed typhoid cases recorded at referral hospitals serving the study areas. Conclusions: If environmental detection of Salmonella Typhi correlates with the incidence of typhoid fever estimated through clinical surveillance, typhoid ES may be a powerful and low-cost tool to estimate the local burden of typhoid fever and support the introduction of typhoid conjugate vaccines. Typhoid ES could also allow the impact of vaccination to be assessed and rapidly identify circulation of drug resistant strains.
The genome sequence of the dark-saddled leucozona, Leucozona laternaria (Muller, 1776)
Authors: Falk Steven ,   University of Oxford and Wytham Woods Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective, Chua Physilia ,   Darwin Tree of Life Consortium
Published: January 2023

We present a genome assembly from an individual female Leucozona laternaria (the dark-saddled leucozona; Arthropoda; Insecta; Diptera; Syrphidae). The genome sequence is 614 megabases in span. Most of the assembly (99.69%) is scaffolded into five chromosomal pseudomolecules including the assembled X sex chromosome. The mitochondrial genome has also been assembled and is 18.3 kilobases in length. Gene annotation of this assembly on Ensembl has identified 11,677 protein coding genes.
Low-frequency broadband multilayer microwave metamaterial absorber based on resistive frequency selective surfaces
Authors: Lan Hao Wen , Li Zhi Ming , Weng Xiao Long , Qi Lun , Li Kai , Zhou Zhang Rong , Wu Xue Yu , Bi Mei 
Published: January 2023

Herein, a low-frequency broadband multilayer metamaterial absorber
(MMA) based on resistive
frequency selective surfaces
(RFSSs) is proposed, which consists of a three-layer RFSS, three-layer
polymethacrylimide (PMI) foam substrates, and a copper film. The
proposed absorber has the advantages of ultra-broadband absorption
with absorptivity more than 90% ranging from 1.91 to 20.78 GHz,
which covers the entire S, C, X, and Ku bands with the thickness of

0.102

λ

L

(where

λ

L

corresponds to the wavelength of the
lowest operating frequency). The absorption performance can keep good
stability in a wide angular range for both TE and TM modes. Moreover,
a prototype of the proposed MMA is fabricated and experimentally
measured to demonstrate its excellent performance. The experimental
results show excellent consistency with numerical simulations.
Numerical study of transmissive liquid crystal Pancharatnam–Berry gratings with small periods
Authors: Liu Sha , Yu Hao , Jiang Miao , Feng Jun , Wei Qi-Huo 
Published: January 2023

Advances in patterning molecular orientations in liquid crystals have made possible the fabrications of various high-quality flat optical elements, ranging from gratings to beam shaping devices. These devices are based on modulating the Pancharatnam–Berry (PB) phase. It is well known that the diffraction efficiency for liquid crystal PB optical elements decreases for large diffraction angles. Here we study this issue using numerical simulations based on finite-difference time-domain algorithms and show that the optical efficiency formula commonly used for liquid crystal gratings deviates significantly from numerical results and is inaccurate for small grating periods because of its assumption that light beams do not diffract inside the liquid crystal films. We show that, for large diffraction angles, the polarization of the diffracted beam is generally elliptically polarized, and we further show that, by using liquid crystal materials with larger birefringence

Δ
n
∼

0.4

, the diffraction efficiency for a grating period of 0.8 µm can go above 90%, which can be used for various flat optical elements with numerical aperture

∼

0.7

.
Monolithic Yb3+-doped thin film lithium niobate microring laser fabricated by photolithography-assisted chemo-mechanical etching technology
Authors: Ma Yu , Zhou Junxia , Fang Zhiwei , Zhou Yuan , Huang Ting , Zhu Yiran , Wang Zhe , Liu Jian , Liu Zhaoxiang , Wu Rongbo , Wang Min , Zhang Haisu , Cheng Ya 
Published: January 2023

We demonstrate an on-chip microring laser on

Y
b

3
+

-doped thin film lithium niobate (Yb:TFLN) fabricated by photolithography-assisted chemo-mechanical etching technology. Multiwavelength laser emissions around 1025 nm from the microring resonator pumped by a 980 nm laser diode are observed with the lasing threshold of 10 mW. Experimentally, up to 14 longitudinal modes are obtained from the fabricated Yb:TFLN microring laser, and this on-chip microring laser is a promising light source for multiple wavelength channels in optical communications and biosensors.