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Wenzhen Ge,1 Ning Wu,1 Chieh-I Chen,1 Timothy J Inocencio,1 Patrick R LaFontaine,2 Frank Seebach,3 Matthew Fury,4 James Harnett,1 Emily S Ruiz5 1Department of Health Economics and Outcomes Research, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 2Department of Global Health Economics & Outcomes Research, Sanofi, Cambridge, MA, USA; 3Department of Regulatory Affairs, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 4Department of Clinical Sciences, Oncology, Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA; 5Department of Dermatology, Dana-Farber Cancer Institute, Boston, MA, USACorrespondence: Wenzhen Ge, Regeneron Pharmaceuticals, Inc, 1 Rockwood Road, Sleepy Hollow, NY, 10591, Tel +1 914-847-7000, Email wenzhen.ge@regeneron.comBackground: Prior to the Food and Drug Administration approval of cemiplimab in 2018, the median overall survival (OS) for adult patients with advanced CSCC receiving systemic therapy was approximately 8 to 15 months. Limited real-world data are available on cemiplimab for this indication in the US.Patients and Methods: This retrospective cohort study included US patients with advanced CSCC initiating cemiplimab monotherapy in a real-world database (2018– 2021). A clinical trial–like sub-cohort was identified using select criteria. Time to treatment discontinuation (TTD), time to next treatment (TTNT), and OS were estimated using Kaplan–Meier methods. Cox proportional hazard models were used to examine prognostic factors associated with OS in the main cohort.Results: The main cohort included 622 patients (n = 240 in the trial-like cohort). In the main cohort, the median age was 78 years, 77.8% were male, 21.4% were immunocompromised/immunosuppressed, and 63.8% had metastatic CSCC. Median (95% CI) TTD and TTNT were 8.0 (6.6– 9.0) months and 16.4 (13.3– 21.0) months, respectively, in the main cohort. Median (95% CI) OS was 24.8 (21.8– 29.1) months in the main cohort (not reached in the trial-like cohort). In multivariable analyses, age < 60 years (hazard ratio [HR], 0.37), Eastern Cooperative Oncology Group performance status < 3– 4 (HR range, 0.13– 0.57), and primary CSCC location in the head and neck only versus extremities only (HR, 0.59) were associated with better OS. Similar OS was observed between patients who had immunosuppressing/immunocompromising conditions and those without.Conclusion: These findings confirm the effectiveness of cemiplimab among a heterogenous, real-world advanced CSCC patient population and substantiate the efficacy of cemiplimab observed in clinical trials.Keywords: cutaneous squamous cell carcinoma, cemiplimab, immune checkpoint inhibitor, real-world study, skin cancer

To address the issue of frequency stability in microgrids with limited communication resources and bandwidth, this paper proposed an event-triggered control method based on a cloud-edge collaborative architecture. Firstly, to address the limited communication resources, event-triggered detector is set up at the edge to upload state variables and update control instructions only when the frequency deviation exceeds a pre-set threshold. Secondly, a fractional-order PI–PD controller is designed at the cloud control center, which achieves higher control degrees of freedom and stronger robustness than traditional integer-order PID control schemes. Additionally, to obtain better control parameters, an optimized design method based on an improved Big Bang-Big Crunch method (BB-BC3) is proposed for the fractional-order PI–PD controller. At last, a simulation example is given to prove the validity of the proposed method. Simulation results show that compared to the integer-order PI–PD controller, the fractional-order PI–PD controller based on the BB-BC3 algorithm proposed in this paper reduces the peak value of the response curve by 5%, and shortens the setting time by 0.14 s. [ABSTRACT FROM AUTHOR]

There are many rotating spheroids in the universe, and many astronomers and physicists have used theoretical methods to study the characteristics of stellar gravity since Newton's time. This paper derives the solutions of eight scattering states (ϕ(0),χ(0),ϕ(1),χ(1),ϕ(2)$$ \Big({\phi}^{(0)},{\chi}^{(0)},{\phi}^{(1)},{\chi}^{(1)},{\phi}^{(2)} $$,χ(2),ϕ(3)$$ {\chi}^{(2)},{\phi}^{(3)} $$, andχ(3))$$ {\chi}^{(3)}\Big) $$ for the Dirac equation with positive‐energy E=im$$ E= im $$, and establishes the relationship between the differential scattering cross section σi(p,θ,φ)$$ {\sigma}_i\left(p,\theta, \varphi \right) $$ and the stellar density μ$$ \mu $$. It is found that: (1) For the eight scattering states, their average scattering cross‐sections σi‾$$ \overline{\sigma_i} $$ are proportional to μ2$$ {\mu}^2 $$, and depend on the star's radius, and the higher the stellar density μ$$ \mu $$, the greater the sensitivity of σi‾$$ \overline{\sigma i} $$ to the change of μ$$ \mu $$; (2) For the four scattering states χ(i),i=0,1,2,3$$ {\chi}^{(i)},i=0,1,2,3 $$, their average scattering amplitudes f‾(p,θ)$$ \overline{f}\left(p,\theta \right) $$ and σ‾(p,θ)$$ \overline{\sigma}\left(p,\theta \right) $$ depend on the mass m$$ m $$ of the particles; while for the other four scattering states ϕ(i)$$ {\phi}^{(i)} $$, i=0,1,2,3$$ i=0,1,2,3 $$, then f‾$$ \overline{f} $$ and σ‾$$ \overline{\sigma} $$ are independent of m$$ m $$. This study links the gravitational characteristics of stars with the scattering cross section, creating a new method for studying the gravitational characteristics, which helps to reveal the mystery of the gravity of rotating ellipsoidal stars. [ABSTRACT FROM AUTHOR]

Selective and concise construction of ring systems that are ubiquitous skeletons across chemistry, drugs and materials, is indispensable for human life. Of note, directed C−H annulation with alkynes for the expedient delivery of ring systems holds great importance, featuring step‐ and atom‐economy, mild conditions, and broad substrate scope. However, regioselectivity issues remained when using unsymmetrical alkynes for the directed C−H annulation. Herein, we summarized recent achievements towards solving this problem by developing directing groups, metal catalysts, and alkynes with versatile and traceless functionality that ensure the overall regioselectivity, enantioselectivity, efficiency, and synthetic application. We hope this concept will promote the further development of the precise construction of functional molecules using C−H annulation with unsymmetrical alkynes. [ABSTRACT FROM AUTHOR]

Planning for autonomous vehicles to merge into high‐density traffic flows within limited mileage is quite challenging. Specifically, the driving trajectory will inevitably have intersections with other vehicles whose driving intentions can't be directly observed. Herein, a two‐stage algorithm framework that is decomposed into the longitudinal and lateral planning processes for online merging planning is proposed. An improved particle filter is used to estimate the driving models of surrounding vehicles for predicting their future driving intentions. Based on Monte Carlo tree search (MCTS), different action spaces are evaluated for longitudinal merging gap selection and lateral interactive merging operation, while heuristic pruning is used to reduce the computation cost. Moreover, the coefficients related to the driving styles are introduced, and their influences on merging performance are analyzed. Finally, the proposed algorithm is implemented in a two‐lane simulation environment. The results show that the proposal has outperformed other baseline methods. [ABSTRACT FROM AUTHOR]

In this article, we consider the resilience problem in the presence of communication faults encountered in distributed secondary voltage and frequency control of an islanded alternating current microgrid. Such faults include the partial failure of communication links and some classes of data manipulation attacks. This practical and important yet challenging issue has been taken into limited consideration by existing approaches, which commonly assume that the measurement or communication between the distributed generations (DGs) is ideal or satisfies some restrictive assumptions. To achieve communication resilience, a novel adaptive observer is first proposed for each individual DG to estimate the desired reference voltage and frequency under unknown communication faults. Then, to guarantee the stability of the closed-loop system, voltage and frequency restoration, and accurate power sharing regardless of unknown communication faults, sufficient conditions are derived. Some simulation results are presented to verify the effectiveness of the proposed secondary control approach. [ABSTRACT FROM AUTHOR]

As an indispensable branch of machine learning (ML), reinforcement learning (RL) plays a prominent role in the decision-making process of autonomous driving (AD), which enables autonomous vehicles (AVs) to learn an optimal driving strategy through continuous interaction with the environment. This paper proposes a deep reinforcement learning (DRL)-based motion planning strategy for AD tasks in the highway scenarios where an AV merges into two-lane road traffic flow and realizes the lane changing (LC) maneuvers. We integrate the DRL model into the AD system relying on the end-to-end learning method. An improved DRL algorithm based on deep deterministic policy gradient (DDPG) is developed with well-defined reward functions. In particular, safety rules (SR), safety prediction (SP) module and trauma memory (TM) as well as the dynamic potential-based reward shaping (DPBRS) function are adopted to further enhance safety and accelerate learning of the LC behavior. For validation, the proposed DSSTD algorithm is trained and tested on the dual-computer co-simulation platform. The comparative experimental results show that our proposal outperforms other benchmark algorithms in both driving safety and efficiency. [ABSTRACT FROM AUTHOR]

In this article, we study the distributed resilient cooperative control problem for directed networked Lagrangian systems under denial-of-service (DoS) attacks. The DoS attacks will block the communication channels between the agents. Compared with the existing methods for the linear networked systems, the considered nonlinear networked Lagrangian systems with asymmetric channels under DoS attacks are more challenging and still not well explored. In order to solve this problem, a novel resilient cooperative control scheme is proposed by using the sampling control approach. Sufficient conditions are first derived in the absence of DoS attacks according to a multidimensional small-gain scheme. Then, in the presence of DoS attacks, the proposed resilient scheme works in a switching manner. Inspired by multidimensional small-gain techniques, the Lyapunov approach is used to analyze the closed-loop system, which enables us to establish sufficient stability conditions for the control gains in terms of the duration and frequency of the DoS attacks. [ABSTRACT FROM AUTHOR]

We propose a novel, computationally efficient, and robust light detection and ranging (LiDAR)-only odometry framework based on truncated least squares termed T-LOAM. Our method focuses on alleviating the impact of outliers to allow robust navigation in sparse, noisy, or cluttered scenarios where degeneration occurs. As preprocessing, the multiregion ground extraction and dynamic curved-voxel clustering methods are proposed to accomplish the segmentation of 3D point clouds and filter out unstable objects. A novel feature extraction module is tailored to discriminate four peculiar features: edge features, sphere features, planar features, and ground features. As frontend, a hierarchical feature-based LiDAR-only odometry performs precise motion estimates through the truncated least squares method for directly processing various features. The preprocessing model and motion estimation precision have been evaluated on the KITTI odometry benchmark as well as various campus scenarios. The experimental results have demonstrated the real-time capability and superior precision of the proposed T-LOAM over other state-of-the-art algorithms. [ABSTRACT FROM AUTHOR]

Proliferative vitreoretinopathy (PVR) is the main cause of retinal detachment surgery failure. The epithelial-mesenchymal transition (EMT) induced by transforming growth factor (TGF-β2) plays an important role in the development of PVR. Artesunate has been widely studied as a treatment for ophthalmic diseases because of its antioxidant, anti-inflammatory, antiapoptotic and antiproliferative properties. The purpose of this study was to investigate the effects of artesunate on the TGF-β2-induced EMT in ARPE-19 cells and PVR development. We found that artesunate inhibited the proliferation and contraction of ARPE-19 cells after the EMT and the autocrine effects of TGF-β2 on ARPE-19 cells. Additionally, the levels of Smad3 and p-Smad3 were increased in clinical samples, and artesunate decreased the levels of Smad3 and p-Smad3 in ARPE-19 cells treated with TGF-β2. Artesunate also inhibited the occurrence and development of PVR in vivo. In summary, artesunate inhibits the occurrence and development of PVR by inhibiting the EMT in ARPE-19 cells. • A conformational activation of Smad signaling pathway in PVR disease. • Artesunate can decreased the activation of TGF/Smad signaling pathway. • Artesunate inhibits the epithelial-mesenchymal transition of ARPE-19 cells induced by TGF. • Artesunate can inhibits PVR progression in vivo. [ABSTRACT FROM AUTHOR]

Introduction: Although cutaneous squamous cell carcinoma (CSCC) is the second most common type of skin cancer, research describing the patient experience is limited. This study sought to create a conceptual model of non-metastatic disease, to assess patient-reported outcome (PRO) instruments commonly used in CSCC against this model, and to develop a patient-relevant measurement strategy for evaluating the benefit of new therapies., Methods: Researchers conducted a literature review, a review of patient blogs, and interviews with dermatologists to draft the conceptual model. A total of 22 patients with CSCC participated in 60-min phone interviews, which were subsequently transcribed, coded, and analyzed; the conceptual model was then updated. PRO instruments used in CSCC were assessed for content validity on the basis of this., Results: The CSCC patient experience includes physical symptoms, psychological impacts, and behavior changes. Existing PRO instruments were assessed against the conceptual model using targeted subdomains considered to be relevant for assessing clinical benefit. Four modules of the FACE-Q ® Skin Cancer instrument, plus de novo items developed for concepts not assessed by the FACE-Q ® [lesion symptoms, negative treatment effects (including symptomatic), and experience of care], provide the best coverage for the concepts of interest hypothesized to show the benefit of novel treatments., Conclusions: This research provides a comprehensive understanding of the experience of patients with non-metastatic CSCC, and the effects of its treatment. It also identifies unmet needs in a subgroup of patients reporting negative treatment experiences. Further cognitive debriefing and psychometric analysis of de novo items are warranted for applications in clinical research., (© 2024. The Author(s).)

Background: Stroke and traumatic intracranial hemorrhage (tICH) are major causes of disability worldwide, with stroke exerting significant negative effects on the brain, potentially elevating tICH risk. In this study, we investigated tICH risk in stroke survivors., Methods and Results: Using relevant data (2017-2019) from Taiwan's National Health Insurance Research Database, we conducted a population-based retrospective cohort study. Patients were categorized into stroke and nonstroke groups, and tICH risk was compared using a Cox proportional-hazards model. Among 164 628 patients with stroke, 1004 experienced tICH. Patients with stroke had a higher tICH risk than nonstroke counterparts (adjusted hazard ratio [HR], 3.49 [95% CI, 3.17-3.84]). Subgroup analysis by stroke type revealed higher tICH risk in hemorrhagic stroke survivors compared with ischemic stroke survivors (HR, 5.64 [95% CI, 4.97-6.39] versus 2.87 [95% CI, 2.58-3.18], respectively). Older patients (≥45 years) with stroke had a higher tICH risk compared with their younger counterparts (<45 years), in contrast to younger patients without stroke (HR, 7.89 [95% CI, 6.41-9.70] versus 4.44 [95% CI, 2.99-6.59], respectively). Dementia and Parkinson disease emerged as significant tICH risk factors (HR, 1.69 [95% CI, 1.44-2.00] versus 2.17 [95% CI, 1.71-2.75], respectively). In the stroke group, the highest tICH incidence density occurred 3 months after stroke, particularly in patients aged >65 years., Conclusions: Stroke survivors, particularly those with hemorrhagic stroke and those aged ≥45 years, face elevated tICH risk. Interventions targeting the high-risk period are vital, with fall injuries potentially contributing to tICH incidence.

Background: There is limited knowledge of how US managed care professionals view and prioritize quality metrics/performance measures, care models, alternative payment models, and clinical pathways in oncology settings., Objective: To characterize payor perspectives on, and the use of, oncology clinical pathways and performance measures in their reimbursement/access decision-making process., Methods: A survey was implemented via SurveyMonkey software and distributed electronically to a national sample of the Academy of Managed Care Pharmacy (AMCP) Market Insights Panel members from July 11 through August 5, 2022. The survey was created by a steering committee based on literature reviews of the current and future oncology care landscapes. The survey consisted of 47 questions, including those to establish respondents' position, responsibilities, and demographics. The results are presented as descriptive statistics for 7 key questions that covered the perceptions and use of quality metrics/performance measures, alternative payment models, and oncology care pathways as prioritized by the steering committee., Results: Among the 695 AMCP panel members who were sent the survey, 73 responded (response rate 10.5%), 54 were eligible to continue, and 31 completed the entire questionnaire; the low response rate may limit generalizability of the survey results. Specific oncology clinical and economic measures of performance were currently used (70%-88%) but generally received less endorsement for future use (39%-49%) except for chemotherapy during end of life, which was considered for future use by 80% of respondents but was only currently used by 31%. Benchmarking was the primary reason for the use of performance measures; only 27% used these to inform value-based agreements. Real-world data tracked by respondents' institutions primarily focused on managed care and pharmacy utilization (39%-85%), with patient-reported and clinical outcomes tracked by only 17%-34%. Almost one-third (31%) did not use clinical oncology pathways, and among those who did, fewer than half (48%) reported that their organization tracks whether treatment decisions agree with the oncology care pathways, and only 26% reported feedback to oncology providers on how often their treatment decisions agree with the pathways. When considering alternative payment models, patient-related components received lower rankings in importance than clinical relevance, actionability, and costs., Conclusions: Variation among payors regarding current trends in oncology care management, including on the importance of patient-centric outcomes and the use of oncology clinical pathways, suggests the need to focus on value-based health care and greater uptake of oncology clinical pathways.

Background: For in vitro fertilization (IVF), mitochondrial DNA (mtDNA) levels in the trophectodermal (TE) cells of biopsied blastocysts have been suggested to be associated with the cells' developmental potential. However, scholars have reached differing opinions regarding the use of mtDNA levels as a reliable biomarker for predicting IVF outcomes. Therefore, this study aims to assess the association of mitochondrial copy number measured by mitoscore associated with embryonic developmental characteristics and ploidy., Methods: This retrospective study analyzed the developmental characteristics of embryos and mtDNA levels in biopsied trophectodermal cells. The analysis was carried out using time-lapse monitoring and next-generation sequencing from September 2021 to September 2022. Five hundred and fifteen blastocysts were biopsied from 88 patients undergoing IVF who met the inclusion criteria. Embryonic morphokinetics and morphology were evaluated at 118 h after insemination using all recorded images. Blastocysts with appropriate morphology on day 5 or 6 underwent TE biopsy and preimplantation genetic testing for aneuploidy (PGT-A). Statistical analysis involved generalized estimating equations, Pearson's chi-squared test, Fisher's exact test, and Kruskal-Wallis test, with a significance level set at P < 0.05., Results: To examine differences in embryonic characteristics between blastocysts with low versus high mitoscores, the blastocysts were divided into quartiles based on their mitoscore. Regarding morphokinetic characteristics, no significant differences in most developmental kinetics and observed cleavage dysmorphisms were discovered. However, blastocysts in mitoscore group 1 had a longer time for reaching 3-cell stage after tPNf (t3; median: 14.4 h) than did those in mitoscore group 2 (median: 13.8 h) and a longer second cell cycle (CC2; median: 11.7 h) than did blastocysts in mitoscore groups 2 (median: 11.3 h) and 4 (median: 11.4 h; P < 0.05). Moreover, blastocysts in mitoscore group 4 had a lower euploid rate (22.6%) and a higher aneuploid rate (59.1%) than did those in the other mitoscore groups (39.6-49.3% and 30.3-43.2%; P < 0.05). The rate of whole-chromosomal alterations in mitoscore group 4 (63.4%) was higher than that in mitoscore groups 1 (47.3%) and 2 (40.1%; P < 0.05). A multivariate logistic regression model was used to analyze associations between the mitoscore and euploidy of elective blastocysts. After accounting for factors that could potentially affect the outcome, the mitoscore still exhibited a negative association with the likelihood of euploidy (adjusted OR = 0.581, 95% CI: 0.396-0.854; P = 0.006)., Conclusions: Blastocysts with varying levels of mitochondrial DNA, identified through biopsies, displayed similar characteristics in their early preimplantation development as observed through time-lapse imaging. However, the mitochondrial DNA level determined by the mitoscore can be used as a standalone predictor of euploidy., (© 2024. The Author(s).)

Aim: To evaluate health-related quality of life (HRQoL) in cemiplimab-treated patients with locally advanced basal cell carcinoma (laBCC). Materials & methods: Eighty-four patients with laBCC received cemiplimab 350 mg every 3 weeks (up to 9 cycles). HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and each cycle. Mixed-effects repeated-measures models evaluated change from baseline across cycles. Results: Clinically meaningful improvement or maintenance was reported by 62-90% of patients on QLQ-C30 scales and by approximately 80% on Skindex-16 scales at Cycle 2, with consistent results at Cycle 9 except fatigue. Conclusion: Most cemiplimab-treated patients with laBCC reported improvement or maintenance of HRQoL with low symptom burden except fatigue. Clinical Trial Registration: ClinicalTrials.gov identifier NCT03132636, registered 28 April 2017.

Policy iteration (PI), an iterative method in reinforcement learning, has the merit of interactions with a little-known environment to learn a decision law through policy evaluation and improvement. However, the existing PI-based results for output-feedback (OPFB) continuous-time systems relied heavily on an initial stabilizing full state-feedback (FSFB) policy. It thus raises the question of violating the OPFB principle. This article addresses such a question and establishes the PI under an initial stabilizing OPFB policy. We prove that an off-policy Bellman equation can transform any OPFB policy into an FSFB policy. Based on this transformation property, we revise the traditional PI by appending an additional iteration, which turns out to be efficient in approximating the optimal control under the initial OPFB policy. We show the effectiveness of the proposed learning methods through theoretical analysis and a case study.

Background: Minimally invasive hemorrhoid surgeries like Doppler-Guided Hemorrhoidal Artery Ligation (DGHAL) and Stapled Hemorrhoidopexy (PPH) offer benefits over traditional methods. This study investigated public perceptions and attitudes towards these surgeries, exploring awareness, preferences, and influencing factors., Methods: A detailed questionnaire was disseminated to 2011 participants from various regions of Taiwan in December 2023, gathering data on demographics, understanding of minimally invasive surgery, and attitudes towards hemorrhoid surgery. Chi-square tests were used for analysis ( p  < 0.05)., Results: Hemorrhoid prevalence was similar across sexes and age groups. About 70 % preferred medical centers or district hospitals for surgery. Postoperative complications were a primary concern, with significant sex differences. Approximately 70 % preferred minimally invasive surgery if costs were below NT$50,000. Medical personnel showed higher awareness of minimally invasive surgery benefits. Most participants relied on personal networks and medical social media for information., Conclusions: The study revealed generally positive perceptions of minimally invasive hemorrhoid surgery, with cost being a significant factor. Knowledge gaps exist, particularly among non-medical personnel. Future initiatives should aim to enhance public awareness of minimally invasive surgery benefits, and policy considerations should address financial aspects of healthcare decisions., Competing Interests: The authors declare that they have no competing interests., (© 2024 The Authors. Published by Elsevier Inc.)

Background: With its minimally invasive approach, laparoscopic surgery has transformed the medical landscape. As the demand for these procedures escalates, there is a pressing need for adept surgeons trained in laparoscopic techniques. However, current training often falls short of catering to medical school education. This study evaluates the impact of a custom-designed laparoscopic training workshop on medical students' surgical skills and career aspirations., Methods: This prospective experimental study was conducted at the E-Da hospital in Kaohsiung City, Taiwan. Medical students from Taiwanese medical schools undergoing Clerk 5, Clerk 6, and Postgraduate Year 1 and 2 were invited to participate. Medical students (n = 44) underwent an endoscopic skill training workshop consisting of lectures, box training, and live tissue training. The trainees performed multiple tasks before and after training using our objective evaluation system. The primary outcome was assessed before and after training through a questionnaire assessing the influence of training on students' interest in surgery as a career. The secondary outcome measured improvement in skill acquisition, comparing the task completion time pre- and post-workshop. For the primary outcome, descriptive statistics were used to summarize the questionnaire responses, and paired t-tests were performed to determine significant changes in interest levels post-workshop. For the secondary outcome, paired t-tests were used to compare the time recorded pre- and post-training., Results: Post-training, participants exhibited significant proficiency gains, with task completion times reducing notably: 97 s (p = 0.0015) for Precision Beads Placement, 88.5 s (p < 0.0001) for Beads Transfer Exercise, 95 s (p < 0.0001) for Precision Balloon Cutting, and 137.8 s (p < 0.0001) for Intracorporeal Suture. The primary outcome showcased an increased mean score from 8.15 pre-workshop to 9.3 post-workshop, indicating a bolstered interest in surgery as a career. Additionally, post-training sentiment analysis underscored a predominant inclination toward surgery among 88% of participants., Conclusion: The custom-designed laparoscopic workshop significantly improved technical skills and positively influenced students' career aspirations toward surgery. Such hands-on training workshops can play a crucial role in medical education, bridging the gap between theoretical knowledge and practical skills and potentially shaping the future of budding medical professionals., (© 2024. The Author(s).)

Background: A phase 2 cemiplimab study (NCT03132636) demonstrated a 24.1% objective response rate in patients diagnosed with metastatic basal cell carcinoma (mBCC) who were not candidates for continued hedgehog inhibitor (HHI) therapy due to intolerance to previous HHI therapy, disease progression while receiving HHI therapy, or having not better than stable disease on HHI therapy after 9 months. Here, health-related quality of life (QoL) for this patient population is reported., Methods: Adult patients with mBCC were treated with intravenous cemiplimab at a dose of 350 mg every 3 weeks for 5 treatment cycles of 9 weeks/cycle then 4 treatment cycles of 12 weeks/cycle. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life-Core 30 (QLQ-C30) and Skindex-16 questionnaires at baseline and Day 1 of each cycle. Across Cycles 2 to 9, the overall change from baseline was analyzed using a mixed model with repeated measures. Responder analyses determined clinically meaningful improvement or deterioration (changes ≥10 points) or maintenance across all scales., Results: Patients reported low symptom burden and moderate-to-high functioning at baseline. Maintenance for QLQ-C30 global health status (GHS)/QoL and across all functioning and symptom scales was indicated by overall mean changes from baseline. Clinically meaningful improvement or maintenance was reported at Cycle 2 for GHS/QoL (77%), functioning scales (77% to 86%), and symptom scales (70% to 93%), with similar proportions of improvement or maintenance at Cycles 6 and 9, excluding fatigue. On the Skindex-16, clinically meaningful improvement or maintenance was reported across the emotional, symptom, and functional subscales, in 76%-88% of patients at Cycle 2, which were generally maintained at Cycles 6 and 9. Overall mean changes from baseline showed maintenance across these subscales., Conclusions: The majority of patients treated with cemiplimab reported improvement or maintenance in GHS/QoL and functioning while maintaining a low symptom burden., (© 2024 Regeneron and The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Objectives : To evaluate the effect of intrauterine infusion and hysteroscopic injection of autologous platelet-rich plasma (PRP) in patients with a persistent thin endometrium (EM) undergoing euploid frozen embryo transfer (EFET) cycles. Methods : This prospective case-control study enrolled 116 infertile women with thin EM (<7 mm) who underwent hormone replacement therapy (HRT) for EFET. These women had experienced at least one previous unsuccessful EFET cycle, which either resulted in the cancellation of the cycle or failure of pregnancy. A total of 55 women received an intrauterine infusion of PRP before FET, 38 received a hysteroscopic injection of PRP, and 23 received standard HRT treatment without PRP (control group). Only euploid embryos were transferred in these cycles. The primary outcomes were the implantation rate (IR) and clinical pregnancy rate (CPR) after EFET. Results : After receiving intrauterine infusion and hysteroscopic injection of PRP, 78.2% and 55.3% of patients, respectively, showed an EM thickness exceeding 7 mm, followed by embryo transfer. The hysteroscopic injection group demonstrated significantly higher IR (52%), a higher trend of CPR (52%), and a higher live birth rate (38%) than the control group (18%, 22%, and 4%). Conclusions : Intrauterine infusion and hysteroscopic injection of autologous PRP may be effective methods to increase EM thickness in HRT cycles. According to our results, both methods could increase EM thickness, while hysteroscopic injection appeared to provide more significant assistance in increasing IR, CPR, and live birth rate after EFET in patients with persistent thin EM.

Gender self-identification (transgender) is not permitted in most Asian countries. In Taiwan, individuals recognized as transgender must meet requirements mandated by the Gender Recognition Act. Currently, lifting the requirement for proof of sex-reassignment surgery is pending. The aim of this study was to survey a large sample of Taiwanese to gain a better understanding of the general population's attitudes toward gender self-identification. A self-report survey, entitled "Opinions of Gender Self-Identification," collected demographic information and responses (agree = 1, disagree = 0) to 14 statements about transgender women and women's safety, personal rights, and the law; one statement discussed rights of transgender men to give birth; total scores ranged from 0 to 14. The online survey was distributed to non-government organizations across Taiwan and the Taiwanese islands and was available between April 16 and 30, 2022. Most of the 10,158 respondents were female (77.4%); ages of respondents ranged from 15 to > 65 years. The mean total score was 0.95 ± 2.27, indicating respondents strongly disagreed with support for transgender females; 91.56% disagreed with all statements. Although there were significant differences in scores between parents and non-parents, and those ≤ 35 years versus ≥ 36 years (p < .01), all strongly disagreed with gender self-identification. Given the majority of respondents were females, survey findings should be regarded with caution. Public acceptance of gender self-identification requires support from its residents. Our findings suggest that gender self-identification has not begun to approach even a moderate level of public support among survey respondents., (© 2024. The Author(s).)

Purpose: Nursing students feel stressed during pediatric clinical practicum due to limited communication encounters with hospitalized children. The purpose of this study was to describe junior nursing college students' experiences of communicating with children during pediatric clinical practicums., Design and Methods: A qualitative phenomenological research design was used. Purposive sampling was used to recruit 18 junior nursing college students who completed their pediatric clinical practicum. Data were collected using semi-structured interviews and were analyzed using Colaizzi's seven-step method for data analysis., Results: Three themes emerged from the data. (1) Difficulties in communicating during initial practicum: fear, rejection, self-doubt of communication abilities, and unfamiliarity with the application of communication techniques posed frustrations among nursing students. (2) Efforts to learn during practicum: self-empowerment, seeking a diverse support system, adjusting communication methods, and striving to establish good relationships allowed nursing students to adapt to the pediatric curriculum. (3) Effective communication at the later stages of practicum: mastering fundamental communication techniques and exercising pediatric therapeutic communication techniques allowed nursing students to feel accomplished., Conclusions: Junior nursing college students initially encountered difficulties and frustration when communicating with children during their pediatric clinical practicum. This study serves as a guide for educators of pediatric nursing to design courses on communication with hospitalized children., Practice Implications: These findings could be used to develop foundation courses on communicating with children for first-time pediatric nursing practicum students; for example, formulating a course on therapeutic play for children that encompasses communication techniques, pediatric ward simulation, and introduction to therapeutic play., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: Since use of major cutaneous surgeries/reconstructions among patients with cutaneous squamous cell carcinoma (CSCC) is not well described, we sought to quantify major cutaneous surgeries/reconstructions among patients with CSCC who were newly diagnosed and for those treated with systemic therapy, stratified by immune status. Methods: We used the Optum ® Clinformatics ® Data Mart database (2013-2020) and Kaplan-Meier estimators to assess risk of surgeries/reconstructions. Results: 450,803 patients were identified with an incident CSCC diagnosis, including 4111 patients with CSCC who initiated systemic therapy. The respective 7-year risks of major cutaneous surgeries/reconstructions were 10.9% (95% CI: 10.7-11.0) and 21.8% (95% CI: 17.6-25.8). Overall risk of major cutaneous surgeries/reconstructions was higher in patients who were immunocompromised than those who were immunocompetent. Conclusion: Approximately one in nine patients with CSCC will undergo ≥1 major cutaneous surgeries/reconstructions within 7 years of diagnosis; the risk increases in patients who initiate systemic therapy and among those who are immunocompromised.

Sod culture (SC) and conventional agriculture (CA) represent two distinct field management approaches utilized in the cultivation of tea plants in Taiwan. In this study, we employed gas exchange and chlorophyll fluorescence techniques to assess the impact of SC and CA methods on the photosynthetic machinery of Camellia sinensis cv. TTES No.12 (Jhinhsuan) in response to variable light intensities across different seasons. In spring, at photosynthetic photon flux densities (PPFD) ranging from 800 to 2,000 μmol photon m -2 s -1 , the net photosynthesis rate (Pn, 10.43 μmol CO 2 m -2 s -1 ), stomatal conductance (Gs, 126.11 mmol H 2 O m -2 s -1 ), electron transport rate (ETR, 137.94), and ΔF/Fm' and Fv/Fm (50.37) values for plants grown using SC were comparatively higher than those cultivated under CA. Conversely, the non-photochemical quenching (NPQ) values for SC-grown plants were relatively lower (3.11) compared to those grown under CA at 800 to 2,000 PPFD in spring. Additionally, when tea plants were exposed to PPFD levels below 1,500 μmol photon m - 2 s - 1 , there was a concurrent increase in Pn, Gs, ETR, and NPQ. These photosynthetic parameters are crucial for devising models that optimize cultivation practices across varying seasons and specific tillage requirements, and for predicting photosynthetic and respiratory responses of tea plants to seasonally or artificially altered light irradiances. The observed positive impacts of SC on maximum photosynthetic rate (Amax), Fv/Fm, Gs, water-use efficiency (WUE), and ETR suggest that SC is advantageous for enhancing the productivity of tea plants, thereby offering a more adaptable management model for tea gardens., (© 2024. The Author(s).)

The objectives of this study were to measure the chlorophyll fluorescence (ChlF) parameters of Barbula indica (Hook.) Spreng and Conocephalum conicum (L.) Dumort subjected to various light intensities (LI) as a reflection of their adaptability to their habitats. The electron transport rate (ETR) of all plants under 500 μmol m -2  s -1 photosynthetic photon flux density (PPFD) was significantly higher than other LI treatments, implying that these plants could be grown under a specific and optimal light intensity adapted to 500 PPFD conditions. As LI increased from 50 to 2,000 PPFD, we observed in all plants increased non-photochemical quenching (NPQ) and photo-inhibitory quenching (q I ) and decreased photosystem II efficiency (ΦPSII), potential quantum efficiency of PSII (F v /F m ), actual PSII efficiency (ΔF/F m '%), and F v /F m %. In addition, energy-dependent quenching (q E ), the light protection system (q E  + q Z  + q T ), and q I increased as ΦPSII decreased and photo-inhibition% increased under 1000, 1500, and 2000 PPFD conditions, suggesting that these plants had higher photo-protective ability under high LI treatments to maintain higher photosynthetic system performance. B. indica plants remained photochemically active and maintained higher q E under 300, 500, and 1000 PPFD, whereas C. conicum q Z  + q T exhibited higher photo-protection under 500, 1000, and 1500 PPFD conditions. These ChlF indices can be used for predicting photosynthetic responses to light induction in different bryophytes and provide a theoretical basis for ecological monitoring., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: The objective was to investigate the relationships among disease characteristics, sarcopenia risk, bone function, sleep quality, depressive symptoms, and health-related quality of life in menopausal women. Additionally, we also examined the potential mediating role of coping in the relationship between these factors and health outcomes for individuals with osteoporosis., Methods: In a cross-sectional approach, 201 participants were referred by a physician from the Family Medicine Department during their outpatient visits at a general hospital in Southern Taiwan. Data collection involved structured one-on-one interviews, and the analysis included descriptive and inferential statistics, along with a structural equation modeling., Results: The participants' bone function was strongly positively related to coping, physical and mental quality of life (QOL), and negatively related to sleep quality and depressive symptoms. The duration of osteoporosis was positively related to pain, sarcopenia risk, sleep quality, but negatively related to bone function, physical and mental QOL. This structural framework explains 36% of the variance in depressive symptoms, 25% in sleep disturbances, 54% in mental QOL, and 72% in physical QOL. The best-fit structural equation modeling showed that physical function, exercise, sarcopenia, pain, and coping were significant predictors of depressive symptoms, with coping acting as a mediator in these relationships., Conclusion: Individuals who employed more active coping strategies exhibited fewer depressive symptoms, better sleep quality, and superior physical and mental QOL. Further, individuals with osteoporosis had lower pain levels, less sarcopenia risk, and higher engaged in exercise presentation improved physical and mental QOL. Future longitudinal research holds the promise of providing deeper insights into these complex relationships., Competing Interests: Declaration of competing interest Hui-Ling Lai, Chun-I Chen, Yu-Ching Lin, Liu-Chun Lu and Chiung-Yu Huang declare that they have no conflict of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of interest Dr Stratigos reports advisory board or steering committee roles for Janssen, Regeneron Pharmaceuticals, Inc, Roche, and Sanofi; and research support from AbbVie, Bristol Myers Squibb, LEO Pharma, Pfizer, Genesis Pharma, and Novartis. Dr Sekulic reports advisory roles for Regeneron Pharmaceuticals, Inc and Roche. Dr Peris reports advisory board roles for AbbVie, LEO Pharma, Janssen, Almirall, Eli Lilly, Galderma, Novartis, Pierre Fabre, Sun Pharma, and Sanofi, outside the submitted work. Dr Bechter reports advisory board roles for Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, and Ultimovacs. Dr Prey reports no conflict of interest. Dr Lewis reports grants and personal fees from Regeneron Pharmaceuticals, Inc, and is now an employee of Regeneron Pharmaceuticals, Inc. Dr Basset-Seguin is a consultant and investigator for Regeneron Pharmaceuticals, Inc, Sanofi, and Sun Pharma. Dr Chang reports advisory roles for Castle, Feldan, Merck, and Regeneron Pharmaceuticals, Inc; and research funding from Regeneron Pharmaceuticals, Inc, Merck, Novartis, and Galderma. Dr Dalle reports research grants and travel fees from Bristol Myers Squibb and Merck Sharp & Dohme; and reports that their spouse is an employee of Sanofi with stock options. Dr Fernández Orland declares no conflict of interest. Dr Licitra reports institutional grants and personal fees from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Debiopharm International SA, Eisai, Novartis, and Roche; institutional grants from Celgene International, Exelixis, Hoffmann-La Roche, IRX Therapeutics, Medpace, Merck Serono, and Pfizer; and personal fees from Sobi, Ipsen, Incyte Biosciences Italy SRL, Doxa Pharma, Amgen, Nanobiotics SA, GSK, AccMed, Medical Science Foundation G. Lorenzini, Associazione Sinapsi, Think 2 IT, Aiom Servizi, Prime Oncology, WMA Congress Education, Fasi, DueCi Promotion SRL, MI&T, Net Congress & Education, PRMA Consulting, Kura Oncology, Health & Life SRL, and Immuno-Oncology Hub. Dr Robert reports grants, personal fees, and advisory board roles for Bristol Myers Squibb, Pierre Fabre, Novartis, Amgen, Merck, Roche, Merck Sharp & Dohme, Sanofi, Biothera, and Ultimovacs. Dr Ulrich reports advisory board and speaker roles for Roche, Sanofi, Regeneron Pharmaceuticals, and Sun Pharma. Dr Hauschild reports institutional funding and personal fees from Amgen, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Merck & Co, Philogen, Pierre Fabre, Provectus, Regeneron Pharmaceuticals, Inc, Roche, Sanofi Genzyme, and Novartis; and consultancy fees from OncoSec, Almirall Hermal, and Sun Pharma. Dr Migden reports advisory roles for and travel fees from Regeneron Pharmaceuticals, Inc, and Sun Pharmaceuticals; an advisory role for Rakuten Medical; and research funding from Regeneron Pharmaceuticals, Inc, and PellePharm. Dr Dummer reports intermittent, project-focused consultant and advisory roles for Novartis, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron Pharmaceuticals, Inc, Alligator, MaxiVAX SA, and touchIME outside the submitted work. Drs Yoo, Inocencio, Chen, Seebach, Lowy, and Fury are employees and shareholders of Regeneron Pharmaceuticals, Inc. Mr Okoye is also an employee and shareholder of Regeneron Pharmaceuticals, Inc. Dr Bassukas reports non-financial support from Leo Pharma and Novartis, and institutional grants from Leo Pharma. Dr Loquai reports personal fees from Roche, Sun Pharma, Bristol Myers Squibb, Merck Sharp & Dohme, Merck, Novartis, Pierre Fabre, Kyowa Kirin, Almirall Hermal, and BioNTech. Dr De Giorgi reports no conflict of interest. Dr Eroglu reports advisory board fees from Regeneron Pharmaceuticals, Inc, Novartis, Pfizer, Genentech, Eisai, OncoSec, and Natera; and research grants from Novartis, Pfizer, and Boehringer Ingelheim. Dr Gutzmer reports documentation fees to their institution from Regeneron Pharmaceuticals, Inc; personal fees and non-financial support from Amgen, Bristol Myers Squibb, Roche Pharma, Merck Serono, Pierre Fabre, Sanofi, and Regeneron Pharmaceuticals, Inc; grants, personal fees, and non-financial support from Novartis; grants and personal fees from Pfizer; grants from Johnson & Johnson; and personal fees from Merck Sharp & Dohme, Almirall Hermal, Sun Pharma, 4SC, and Immunocore. Dr Ulrich reports grants and personal fees from Sanofi, Bristol Myers Squibb, Novartis, and Merck Sharp & Dohme; and personal fees from Roche, medac, and Sun Pharma. Dr Puig reports personal fees and non-financial support from Sanofi, Regeneron Pharmaceuticals, Inc, and Pfizer; grants from Avene; non-financial support from MAVIG, FotoFinder, 3Gen, AbbVie, Eli Lilly, and Merck Sharp & Dohme; grants, personal fees, and non-financial support from ISDIN, La Roche-Posay, and Roche; grants and personal fees from Sun Pharma, Leo Pharma, and Almirall; and personal fees from Ojer Pharma and Pierre Fabre. Dr LaFontaine reports employment at Sanofi and holds shares or stock in the company.

Agenesis and hypoplasia affecting multiple flexor tendons within the same hand represent an exceedingly uncommon occurrence, with no previous studies addressing this condition. This report details a 4-year-old girl with agenesis of the right third and fourth fingers, who sought consultation due to the inability to flex her seemingly unaffected second and fifth fingers. Ultrasound examination revealed substantial thinning of the flexor tendons in the second to fifth digits, with a notable absence of attachment to the middle phalanx. In addition to flexor tendon hypoplasia, hypoplasia of the third and fourth middle phalanges was observed. Hand deformities featuring both finger agenesis and flexor tendon hypoplasia across multiple fingers were exceptionally rare. In such instances, ultrasound, in conjunction with radiography, emerges as the recommended initial imaging tool for comprehensive evaluation of both the phalangeal bones and flexor tendons.

Background: Several studies have demonstrated that iDAScore is more accurate in predicting pregnancy outcomes in cycles without preimplantation genetic testing for aneuploidy (PGT-A) compared to KIDScore and the Gardner criteria. However, the effectiveness of iDAScore in cycles with PGT-A has not been thoroughly investigated. Therefore, this study aims to assess the association between artificial intelligence (AI)-based iDAScore (version 1.0) and pregnancy outcomes in single-embryo transfer (SET) cycles with PGT-A., Methods: This retrospective study was approved by the Institutional Review Board of Chung Sun Medical University, Taichung, Taiwan. Patients undergoing SET cycles (n = 482) following PGT-A at a single reproductive center between January 2017 and June 2021. The blastocyst morphology and morphokinetics of all embryos were evaluated using a time-lapse system. The blastocysts were ranked based on the scores generated by iDAScore, which were defined as AI scores, or by KIDScore D5 (version 3.2) following the manufacturer's protocols. A single blastocyst without aneuploidy was transferred after examining the embryonic ploidy status using a next-generation sequencing-based PGT-A platform. Logistic regression analysis with generalized estimating equations was conducted to assess whether AI scores are associated with the probability of live birth (LB) while considering confounding factors., Results: Logistic regression analysis revealed that AI score was significantly associated with LB probability (adjusted odds ratio [OR] = 2.037, 95% confidence interval [CI]: 1.632-2.542) when pulsatility index (PI) level and types of chromosomal abnormalities were controlled. Blastocysts were divided into quartiles in accordance with their AI score (group 1: 3.0-7.8; group 2: 7.9-8.6; group 3: 8.7-8.9; and group 4: 9.0-9.5). Group 1 had a lower LB rate (34.6% vs. 59.8-72.3%) and a higher rate of pregnancy loss (26% vs. 4.7-8.9%) compared with the other groups (p < 0.05). The receiver operating characteristic curve analysis verified that the iDAScore had a significant but limited ability to predict LB (area under the curve [AUC] = 0.64); this ability was significantly weaker than that of the combination of iDAScore, type of chromosomal abnormalities, and PI level (AUC = 0.67). In the comparison of the LB groups with the non-LB groups, the AI scores were significantly lower in the non-LB groups, both for euploid (median: 8.6 vs. 8.8) and mosaic (median: 8.0 vs. 8.6) SETs., Conclusions: Although its predictive ability can be further enhanced, the AI score was significantly associated with LB probability in SET cycles. Euploid or mosaic blastocysts with low AI scores (≤ 7.8) were associated with a lower LB rate, indicating the potential of this annotation-free AI system as a decision-support tool for deselecting embryos with poor pregnancy outcomes following PGT-A., (© 2024. The Author(s).)