bluuebunny/crossref_metadata_2025_split huggingface dataset:
Open-label, prospective phase 2 study to evaluate the efficacy and safety of camrelizumab combined with etoposide and cisplatin as neoadjuvant therapy in patients with neuroendocrine carcinoma of the cervix.
Authors: He Haixin , Yu Haijuan , Lin Cuibo , Lu Yongwei , Chen Jian 
Published: July 2024

TPS5624 Background: Camrelizumab, a humanized monoclonal antibody, specifically targets PD-1 to inhibit its interaction with PD-L1, thereby reactivating the T cell immune response against tumors. The NACI study demonstrated that, in the treatment of locally advanced cervical cancer, the combination of camrelizumab and neoadjuvant chemotherapy achieved an overall response rate (ORR) of 100%. Specifically, complete remission was observed in 4 patients (8.33%), while 44 patients (91.67%) experienced partial remission. This regimen significantly outperformed traditional treatments in efficacy, with manageable toxicity levels. Neuroendocrine carcinoma of the cervix (NECC) is a highly rare and aggressive malignancy characterized by its distinctive biological behavior, propensity for early lymph node and hematogenous metastasis, and limited effective treatment options, leading to a dismal prognosis. Although PD-1 inhibitors have shown promise in some NECC case reports, there is a notable absence of comprehensive, prospective clinical trials to substantiate their effectiveness. This study aims to assess the efficacy and safety of neoadjuvant chemo-immunotherapy in patients with NECC. Methods: This open-label, single-arm, prospective phase II study evaluates the antitumor efficacy and safety of camrelizumab in combination with etoposide and cisplatin in roughly 30 patients with NECC. Eligible participants are aged 18-75, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and histologically confirmed NECC, specifically targeting small cell and large cell neuroendocrine cervical carcinoma but excluding atypical and typical carcinoid tumors. Inclusion criteria stipulate that if NECC is present alongside other tumor types, the neuroendocrine carcinoma component must account for more than 60% of the tumor mass. The treatment protocol involves neoadjuvant chemo-immunotherapy, comprising two to three cycles of camrelizumab (200 mg, IV, day 1), cisplatin (75 mg/m², IV, day 1), and etoposide (100 mg/m², IV, days 1-3) administered every three weeks. Following this, patients achieving complete or partial response will proceed to radical surgery and adjuvant therapy, while those with stable or progressive disease, or considered unsuitable for surgery by gynecological oncologists, will transfer to concurrent chemoradiotherapy. The primary objective is to ascertain the objective response rate as per the Response Evaluation Criteria in Solid Tumors version 1.1. Secondary objectives include disease control rate, progression-free survival, overall survival, and evaluations of safety and tolerability. The study began on December 28, 2023, with ongoing enrollment. Clinical trial information: NCT05910177 .
SB221: A proof-of-concept study to assess the combination of SON-1010 (IL12-FHAB) and atezolizumab in patients with platinum-resistant ovarian cancer.
Authors: Chawla Sant P. , Gao Bo , Bampton Carolyn L. , Hamilton Brett , Cini John K. , Dexter Susan , Kenney Richard T. , Wenham Robert Michael 
Published: July 2024

TPS5629 Background: Recombinant interleukins (rIL) have had limited clinical success due to inefficient tumor targeting and short PK, requiring frequent dosing that leads to aberrant immunostimulation and toxicity. IL-12 potently activates T and NK cells to produce IFNγ and kill tumor cells, yet dosing strategies have failed to provide adequate therapeutic benefit in humans. We developed a novel platform that delivers immunomodulator(s) linked to a fully-human albumin binding (FHAB) domain (Cini, Front Immunol 2023). Single-chain native IL-12 genetically linked to the FHAB provides enhanced tumor targeting and retention through albumin binding to over-expressed FcRn, GP60, and SPARC in the tumor microenvironment (TME), with an improved PK profile, a dose-sparing effect that decreases the toxicity risk, and a broader therapeutic index. Tumor growth inhibition in an immunologically ‘cold’ B16-F10 mouse melanoma model showed the efficacy of IL12-FHAB compared with rIL-12, resulting in significant increases in activated NK, NKT, Th1, and cytotoxic CD8 T cells. SON-1010 is being studied clinically as monotherapy (study SB101) in advanced solid tumors and in healthy volunteers (study SB102) (Chawla, AACR 2023). Atezolizumab (Tecentriq), an anti-PD-L1 immune checkpoint inhibitor (ICI), has shown preliminary clinical activity in Phase 1 studies of patients with platinum-resistant ovarian cancer (PROC) (Liu, Gyn Onc 2019; Moroney, Clin Canc Res 2020). SON-1010 may ‘warm up’ the TME to improve ICI effectiveness in these immunologically-active tumors that have high levels of SPARC. Methods: Study SB221 is a Phase 1b/2a multicenter, dose-escalation and proof-of-concept study to assess the safety, tolerability, PK, PD, and efficacy of SON-1010 administered SC, either alone or in combination with a fixed dose of atezolizumab given IV (NCT05756907). The study is designed in Part 1 to rapidly establish the maximum tolerated dose (MTD) of the combination in patients with advanced solid tumors with up to 5 dose-escalation groups and to expand the dataset using patients with PROC to establish the Recommended Phase 2 Dose (RP2D). Once the likelihood of efficacy is shown in a Simon 2-stage design, this will be followed in Part 2 by an assessment of the potential for improved efficacy of the combination in patients with PROC over SON-1010 alone or the standard of care (SOC). The first dose-escalation cohorts have been enrolled and additional sites are being added to help with recruitment of patients with PROC. Combination of SON-1010 with an ICI offers a unique opportunity to use this extended PK version of IL-12 to augment the potential for tumor control in PROC, which represents a significant unmet medical need. Clinical trial information: NCT05756907 .
Approach to the Patient: New Era Emerges for Craniopharyngioma Management
Authors: Hayes Annabelle G , Jonker Benjamin , Teng Christina , Lemech Charlotte , Killen Andrew J , Sim Hao-Wen , McCormack Ann I 
Published: July 2024

Abstract
Papillary craniopharyngioma (PCP) and adamantinomatous craniopharyngioma (ACP) are distinct, slow-growing tumors of the suprasellar region. Their location, composition, and biology have historically evaded successful surgical radiation and medical therapy. Meanwhile compromise of critical structures either by tumor or treatments increase morbidity, impacting patient and carer quality of life. There has been a paradigm shift in the management of PCP, stemming from the discovery of BRAFV600E mutation in its tumorigenesis. Such a treatment breakthrough may soon be the case for ACP, changing the landscape of craniopharyngioma management. We use a case of ACP partially responding to ERK inhibitor therapy to demonstrate chronicity of disease progression and discuss modern management strategies highlighting the importance of access to tumor agnostic clinical trials, and future directions.
Racial and Ethnic Underserved Populations Prescription Analgesic Use Before and After Lower Extremity Amputation in US Medicare
Authors: Yang Seonkyeong , Wilson Debbie L. , Zhou Lili , Fernandes Deanna C. , Bell Melanie , Tan Tze-Woei , Kwoh Chian Kent , Chang Ching-Yuan , Huang Pei-Lin , Barker Paige C. , Yan Shunhua , Lo-Ciganic Wei-Hsuan 
Published: July 2024

BACKGROUND:
Racial disparities exist in access to health care and management of multiple health conditions including chronic pain; however, racial disparities in pre- and postoperative pain management in lower extremity amputation are not well-studied. Our objective was to examine the association between different racial and ethnic groups and prescription opioid and other analgesics use before and after lower extremity amputation. We hypothesize prescription opioid and other analgesic use among Black, Hispanic, and Native American US Medicare beneficiaries undergoing lower extremity amputations will be lower compared to White US Medicare beneficiaries.

METHODS:
This retrospective cohort study included a 5% national sample of all Medicare beneficiaries from 2011 to 2015 and 15% national sample of fee-for-service Medicare beneficiaries from 2016 to 2018 undergoing nontraumatic, lower extremity amputations. The exposure of interest was racial and ethnic group membership (ie, Black, Hispanic, Native American, White, and others—with others being the combination of the categories Asian and other) as provided in Medicare claims data. Using multivariable generalized estimating equations with a logistic link to account for repeated measurements over time, we estimated the odds of prescription opioid use within 6 months before and after lower extremity amputation across different racial and ethnic groups separately, adjusting for sociodemographic and health status factors (eg, Elixhauser index). Adjusted odds ratios (aORs) and 95% confidence intervals (95% CI) were reported.

RESULTS:
Among 16,068 eligible beneficiaries who underwent major and minor amputations (mean age = 65.1 ± 12.7 years; female = 36.1%), 10,107 (62.9%) were White, 3462 (21.5%) were Black, 1959 (12.2%) were Hispanic, 247 (1.5%) were Native American, and 151 (2.9%) were beneficiaries of other races. During the 6 months before lower extremity amputation, Hispanic beneficiaries (aOR, 0.71, 95% CI, 0.65–0.78) and beneficiaries of other races (aOR, 0.60, 95% CI, 0.47–0.76) had significantly lower odds of using prescription opioids compared to White beneficiaries. Similarly, Hispanic beneficiaries (aOR, 0.78, 95% CI, 0.71–0.84) and beneficiaries of other races (aOR, 0.63, 95% CI, 0.51–0.78) were associated with lower odds of opioid use in the 6 months after amputation compared to White beneficiaries.

CONCLUSIONS:
Among fee-for-service Medicare beneficiaries, Hispanic and other (eg, Asian) fee-for-service Medicare beneficiaries had lower odds of prescription opioid use than their White counterparts before and after nontraumatic, lower extremity amputations. Efforts to determine the underlying reasons are needed to ensure equitable health care access.
Tsunamis versus extreme meteorological waves: Evidence from the 2004 Aegean Sea cyclone in Samos Island
Authors: Stiros Stathis 
Published: July 2024

In January 2004 a Mediterranean cyclone in the Aegean Sea seriously affected the north coast of Samos Island, damaged the harbour mole of a coastal village, and catapulted its building material along with heavy boulders to the inner harbour basin. This area was also affected by a 2020, magnitude 7.0 earthquake which produced localized tsunamis. The evidence from the 2004 cyclone, with boulders shifted from known positions and with known trajectories, can contribute to the debate for the causes of mobilization of coastal boulders because of storms, tsunamis, or their combination.
Self-Guided Approximate Linear Programs: Randomized Multi-Shot Approximation of Discounted Cost Markov Decision Processes
Authors: Pakiman Parshan , Nadarajah Selvaprabu , Soheili Negar , Lin Qihang 
Published: July 2024

Approximate linear programs (ALPs) are well-known models based on value function approximations (VFAs) to obtain policies and lower bounds on the optimal policy cost of discounted-cost Markov decision processes (MDPs). Formulating an ALP requires (i) basis functions, the linear combination of which defines the VFA, and (ii) a state-relevance distribution, which determines the relative importance of different states in the ALP objective for the purpose of minimizing VFA error. Both of these choices are typically heuristic; basis function selection relies on domain knowledge, whereas the state-relevance distribution is specified using the frequency of states visited by a baseline policy. We propose a self-guided sequence of ALPs that embeds random basis functions obtained via inexpensive sampling and uses the known VFA from the previous iteration to guide VFA computation in the current iteration. In other words, this sequence takes multiple shots at randomly approximating the MDP value function with VFA-based guidance between consecutive approximation attempts. Self-guided ALPs mitigate domain knowledge during basis function selection and the impact of the state-relevance-distribution choice, thus reducing the ALP implementation burden. We establish high-probability error bounds on the VFAs from this sequence and show that a worst-case measure of policy performance is improved. We find that these favorable implementation and theoretical properties translate to encouraging numerical results on perishable inventory control and options pricing applications, where self-guided ALP policies improve upon policies from problem-specific methods. More broadly, our research takes a meaningful step toward application-agnostic policies and bounds for MDPs. This paper was accepted by Chung Piaw Teo, optimization. Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2020.00038 .
Cardiac transplantation and dentistry
Authors: Abed Hassan , Kaka Shazia , Boyle Carole , Sherwin Emily 
Published: July 2024

The number of cardiac transplants carried out each year within the UK is increasing. With this rise in numbers, it is important that dental professionals are aware of both pre- and post-operative considerations for these patients. This paper considers the practical elements of managing these patients, outlining important aspects of history taking, treatment planning, and safe pain and anxiety management options. CPD/Clinical Relevance: The unilateral sagittal split osteotomy may present an alternative method for removing impacted mandibular third molar teeth in certain situations.
THE POTENTIAL IMPACT OF A SINGLE-SURGEON APPROACH COMPARED TO A DUAL SURGEON APPROACH ON THE REDISLOCATION RATE FOLLOWING OPEN REDUCTION IN THE MANAGEMENT OF DEVELOPMENTAL DYSPLASIA OF THE HIP IN CHILDREN
Authors: Clarke M. , Segura M. , Cox D. , Horner M. , Kiely N. , Williams D. 
Published: July 2024

IntroductionDevelopmental dysplasia of the hip (DDH) can be managed through a variety of different surgical approaches from closed reduction to simple tenotomies of the adductors and through to osteotomies of the femur and pelvis. The rate of redislocation following open reduction for the treatment of DDH may be affected by the number of intraoperative surgeons.Materials and methodsWe performed a retrospective cohort analysis of 109 patients who underwent open reduction with or without bony osteotomies as a primary intervention between 2013 and 2023. We measured the number of redislocations and number of operating surgeons (either 1 or 2 operating surgeons) to assess for any correlation. 109 patients were identified and corresponded to 121 primary hip operations, the mean age at operation was 82.2 months (range 6 to 739 months). During the 10-year period 7 hip redislocations were identified.ResultsOf the 7 redislocated hips, the rate of redislocation was found to be higher in patients who had undergone surgery via a single surgeon (5 redislocations) compared to the dual surgeon cohort (2 redislocations), though this did not reach statistical significance. Redislocation was more common in female patients and right laterality 7.2% and 8.7% respectively, though this again did not reach statistical significance.ConclusionsWe conclude that a single surgeon approach, female gender and right laterality are potential risk factors for redislocation following open reduction. Further investigation utilising a larger sample size would be required to appropriately explore these potential risk factors further.
ROTATIONAL AND ANGULAR MALALIGNMENT FOLLOWING TITANIUM ELASTIC NAILING SYSTEM AND HIP SPICA CAST FOR FEMUR DIAPHYSEAL FRACTURES IN FOUR- TO SIX-YEAR-OLD CHILDREN: A RANDOMIZED PROSPECTIVE STUDY
Authors: Singh A. , Raulo B. C. , Das P. B. , Dash A. , Zeon N. 
Published: July 2024

Femoral shaft fractures are fairly common injuries in paediatric age group. The treatment protocols are clear in patients of age less than 4 years and greater than 6 years. The real dilemma lies in the age group of 4–6 years. The aim of this study is to find whether a conservative line should be followed, or a more aggressive surgical intervention can provide significantly better results in these injuries.This study was conducted in a tertiary care hospital in Bhubaneswar, India from January 2020 to March 2021. A total of 40 patients with femur shaft fractures were included and randomly divided in two treatment groups. Group A were treated with a TENS nail while group B were treated with skin traction followed by spica cast. They were regularly followed up with clinical and radiological examination to look out for signs of healing and any complications. TENS was removed at 4–9 months’ time in all Group A patients.Group A patients had a statistically significant less hospital stay, immobilisation period, time to full weight bearing and radiological union. Rotational malunions were significantly lower in Group A (p-value 0.0379) while there was no statistically significant difference in angular malunion in coronal and sagittal plane at final follow up. Complications unique to group A were skin necrosis and infection.We conclude that TENS is better modality for treatment of shaft of femur fractures in patients of 4–6 years age as they significantly reduce the hospital stay, immobilization period and rotational malalignment.
THE USE OF A TIBIA REDUCTION DEVICE IN THE TREATMENT OF FRACTURES UNDERGOING TIBIAL NAILING AT A DISTRICT GENERAL HOSPITAL: A PARALLEL CASE SERIES
Authors: Hossain T. , Kimberley C. , Starks I. , Barlow T. , Barlow D. 
Published: July 2024

Malalignment is a common complication following tibial surgery, occurring in 10% of fractures. This is associated with prolonged healing time and non-union. It occurs due to inability to maintain a satisfactory reduction. A reduction device, such as the Staffordshire Orthopaedic Reduction Machine (STORM), permits the surgeon to manipulate the fracture and hold it reduced.A retrospective parallel case series was undertaken of all patients undergoing tibial nails over a six-year period from 2014 to 2021. Patient demographics were obtained from medical records. Operative times obtained from the theatre IT system and included the time patient entered theatre and surgical start and finish times for each case.Anteroposterior and lateral long leg post-operative radiographs were reviewed. Angulation was measured in both coronal and sagittal planes, by two separate orthopaedic surgeons. A reduction was classified to be ‘mal-aligned’ if the angle measured was greater than 5 degrees. One tailed unpaired t-test was used to compare alignment in each plane. Bony union was assessed on subsequent radiographs and was determined according to the Radiographic Union Score for Tibial Fractures31 patients underwent tibial nail during the time period. 8 patients were lost to follow up and were excluded. Of the remaining 23 patients, the STORM device was utilised in 11.The overall mean alignment was acceptable across all groups at 2.17° in the coronal plane and 2.56° in the saggital plane. Analysing each group individually demonstrated an improved alignment when STORM was utilised: 1.7° (1°–3°) vs 2.54° (0°–5°) for the coronal plane and 1.6° (0°–3°) vs 3.31° (0°–9°) in the saggital plane. This difference was significant in saggital alignment (p=0.03) and showed a positive trend in coronal alignment, although was not significant (p=0.08)The time in theatre was shorter in the control group with a mean of 113 minutes (65 to 219) in comparison to STORM with a mean of 140 minutes (105 to 180), an increased theatre time of 27 minutes (p=0.04).This study demonstrates that STORM can be used in the surgical treatment of tibial fractures resulting in improved fracture alignment with a modest increase in theatre time.
Las Funciones ejecutivas en el marco de la Neuroeducación.
Authors: Parrado Torres Henry Giovanni 
Published: July 2024

El auge de las neurociencias y su inclusión en los sistemas escolares abren un sendero inédito hacía la transformación del rol docente, que debe conducir a los educadores a la deconstrucción de sus prácticas educativas, a la actualización de sus propuestas metodológicas y al perfeccionamiento de sus didácticas. Un maestro que conoce como aprende el cerebro, los procesos que se encuentran inmersos y la forma idónea de estimularlo, hace más eficientes y significativos los ambientes de enseñanza, mejora los aprendizajes de sus estudiantes y forma individuos con mayor potencial emocional, social y humano. Acorde a lo anterior y validando la importancia de estos argumentos, el presente artículo hace un reconocimiento y análisis minucioso de las intervenciones centradas en las funciones ejecutivas desarrolladas en contextos educativos del 2018 en adelante, con la intención de identificar de forma holística e integradora los distintos factores, acciones y características que hacen de estos programas de estimulación propuestas exitosas, a fin de obtener orientaciones, sugerencias o criterios que permitan a los lectores y el escritor moldear propuestas educativas en función de la neuroeducación y continuar evidenciando la necesidad de su inserción edificante en los sistemas educativos actuales, los cuales apuntan hacia una camino de calidad, en el cual la neuroeducación puede ser una gran aliada.
Modeling and simulation of optical system error transmission in the laser tracker
Authors: Qiao Xiaoxu , Wang Xiaodong , Gong Jianguo , Luo Yi 
Published: July 2024

The optical system of the laser tracker utilizes plane mirrors to construct a reflective path, reducing its size and weight. However, maintaining the alignment of the laser with the ideal optical axis during its propagation in the optical system poses significant challenges in the design, fabrication, and assembly of the optical system. This paper explores the principle of error propagation during the assembly process of the optical system and improves the accuracy of the output laser through a numerical simulation and optimization methods. A general error model for the optical system is established to understand the principle of error propagation. A Monte Carlo numerical simulation and sensitivity analysis are used to study the influence of various errors on the accuracy of the output laser. The machining errors are optimized using a simulated annealing method to balance the manufacturing difficulty and system accuracy. The assembly process is also optimized to reduce the degrees of freedom and the number of optical parts required, and verified by experiments. The experimental results indicate that the average position error of the output laser is 15.743 µm, and the average angle error is 1.427′′. This study provides what we believe is a novel approach and methodology for the design and alignment of optical systems.