bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapy plus PD-1/PD-L1 inhibitor versus chemotherapy alone in first-line treatment for recurrent or advanced endometrial cancer: A systematic review and meta-analysis of randomized controlled trials.
Authors: de Liz Caio Dabbous , Maia Melissa , Alves Ana Caroline Fonseca , Silva Isadora Mamede Mendes da , Oliveira João Pedro , Oliveira Audrey Cabral Ferreira de 
Published: June 2024

e17597 Background: More recently, the standard of care for primary advanced or recurrent DNA mismatch repair deficient (MMRd)/microsatellite instability-high (MSI-H) endometrial carcinoma has become a combination of chemotherapy (CT) and PD-1/PD-L1 inhibitor. Whether this should also be applied to all-comers and MMRp/MSS population is still an open question. Methods: PubMed, Embase, and Cochrane database were searched for randomized controlled trials (RCTs) comparing first-line CT plus PD-1/PD-L1 inhibitor versus CT, with or without (w/w) placebo, for patients with primary advanced or recurrent endometrial cancer. The primary endpoints of interest were progression free survival (PFS), overall survival (OS), overall response rate (ORR), complete response rate (CRR), and adverse events (AE) grade ≥ 3. Heterogeneity was examined with I2 statistics, and a fixed-effects model was employed for analysis. Statistical analysis was performed using Review Manager Web. Results: We included 5 RCTs with 2460 patients, of whom 1143 (46.5%) received CT plus PD-1/PD-L1 inhibitor, and 1672 (68.0%) had MMRp/MSS tumors. Mean follow-up ranged from 7.9 to 28.3 months. The combination of CT plus anti-PD-1/PD-L1 demonstrated superiority in PFS (HR 0.72; 95% CI 0.65-0.80; p < 0.0001) and OS (HR 0.77; 95% CI 0.65-0.91; p=0.002), compared to CT w/w placebo in the all-comer population. In MMRd/MSI-H patients, PFS (HR 0.34; 95% CI 0.27-0.44; p < 0.00001) and OS (HR 0.37; 95% CI 0.24-0.59; p < 0.0001) were statistically significantly better in combination group. For patients with MMRp/MSS disease, PFS was improved (HR 0.76; 95% CI 0.68-0.86; p < 0.0001), but OS was not significantly different between groups (HR 0.92; 95% CI 0.74-1.14; p=0.44). CT plus PD-1/PD-L1 inhibitor also led to a higher ORR (OR 1.50; 95% CI 1.13-2.00; p=0.006) and CRR (OR 1.56; 95% CI 1.12-2.18; p=0.009) in MMRp/MSS patients. AE grade ≥ 3 were more often when immune checkpoint inhibitor was added (HR 1.46; 95% CI 1.23-1.75; p < 0.0001). Conclusions: These findings suggest that combining PD-1/PD-L1 inhibitor to CT improves PFS, but not OS, in first-line treatment for recurrent or advanced MMRp/MSS endometrial cancer, despite grater toxicity. It supports the hypothesis that the benefit seen in survival for all-comer population appears to be driven by MMRd/MSI-H patients. However, given the immaturity of OS data, it is possible that the higher rate of complete responses may translated into more cured patients in long-term follow-up.
Predictive analysis of placental site trophoblastic tumors (PSTT) and epithelioid trophoblastic tumors (ETT) using machine learning.
Authors: Alenezy Abdalwahab , Alshwayyat Sakhr Abdulsalam , Alshwayyat Mustafa , Alshwayyat Tala Abdulsalam 
Published: June 2024

e17608 Background: The characteristics and outcomes of PSTT and ETT have not been well documented. To improve personalized care, machine learning was used to assess treatment effectiveness and develop accurate prognostic models. Gestational choriocarcinoma (GCC) was used as a control to emphasize the clinical features of PSTT and ETT. Methods: The Surveillance, Epidemiology, and End Results database provided the data used for this study’s analysis (2000–2019). Patients who met any of the following criteria were excluded: diagnosis not confirmed by histology, previous history of cancer or other concurrent malignancies, or unknown data. To identify prognostic variables, we conducted Cox regression analysis and constructed prognostic models using machine learning (ML) algorithms to predict the 5-year survival. Patient records were randomly divided into training (70 %) and validation (30 %) sets. A validation method incorporating the area under the curve (AUC) of the receiver operating characteristic curve was used to validate the accuracy and reliability of the ML models. Results: The study population comprised 725 patients. Among them, 139 patients had ETT, 107 had PSTT, and 479 had GCC. The median patient age was 37 years. Most of the patients were of white race (62.3%) and more than half were married (52.7%). The most common stage of primary tumor histology was distant metastasis, which occurred in 330 patients. The average tumor size was 6.13 cm. More than two-thirds of patients underwent chemotherapy (75.9%), 57.9% underwent surgery, and 4.3% underwent radiotherapy. There were no significant differences in survival between the different tumor groups. Multivariate Cox regression analysis revealed that older age, marital status, metastasis, and radiotherapy were poor prognostic factors, while surgery was a good prognostic factor. ML models revealed that the random forest classifier (RFC) accurately predicted the outcomes. The most important characteristics that influenced the model prediction performance were tumor size, years of diagnosis, race, and age. The performance metrics for all ML algorithms are summarized in Table. Conclusions: Our research sheds light on crucial aspects of clinical decision-making, emphasizing the significance of key factors affecting patient outcomes and offering hope for personalized treatment. Further research should explore the molecular markers and validate the generalizability of our findings. [Table: see text]
Participation of patients with gynecological cancer in phase 1 clinical trials: Experience from 2 NCI-Designated Comprehensive Cancer Centers.
Authors: Adkoli Anusha , Vera Krystle , Glennan Patrick , Yeung Kevin , Aguilar Demmie , Ghalib Mohammad , Chaudhary Imran , Maitra Radhashree , Girda Eugenia , Goel Sanjay 
Published: June 2024

e17610 Background: Phase 1 trials are intended to define the safety of novel therapeutics, yet they offer alternate options long before they are approved. There is limited data regarding access and participation in phase 1 trials for gynecologic oncology patients. The purpose of this study is to assess the efficacy of phase 1 trials and to study factors of demographics, tumor characteristics, and toxicities impacting this population group. Methods: This IRB approved study was conducted via retrospective chart review at the Rutgers Cancer Institute of New Jersey and the Montefiore Einstein Comprehensive Cancer Center. Relevant variables were collected for all gynecologic oncology patients enrolled in phase 1 trials between 2000-2022. Data analysis was completed in a primarily descriptive manner. Results: Of the 335 patients enrolled, 72.2% were < 65 years of age; diagnoses of the 335 patients included ovarian/fallopian tube/peritoneal/mullerian (58.0%), uterine (26.3%), cervical (15.2%), vaginal (0.3%), and vulvar (0.3%) cancers. Patients were 50.5% White, 24.2% Black, 18.2% Hispanic, and 6.6% Asian. Trend over-time analysis (enrollment between 2000-2011 compared to 2012-2022) showed that enrollment of White patients stayed stable (51.0/50.4%), Hispanic (16.0/21.6%) and Asian (3.1%/11.5%) increased, while enrollment decreased for Black patients (29.9/16.5%). Most patients had an ECOG performance status of 1 (74.0%). Prior number of regimens received by patients included 1-3 (52.0%), 4-7 (38.1%), and 8 or more (9.4%). The median number of prior lines was 3. Metastatic disease sites included lymph nodes (51.3%), abdominal/pelvic cavity (39.4%), lung (35.8%) and liver (34.0%). Highest grade hematologic toxicities were 3 or 4 in 18.2% of patients. For non-hematologic toxicities, 28% of patients experienced grade 3-5 events. Among non-hematologic adverse events, the most common grade 3-5 events were fatigue (1.2%), diarrhea (1.1%), vomiting (0.9%), and pain (0.9%). Only 3.9% had a dose limiting toxicity. Efficacy included complete response in 1.2%, partial response in 7.0%, stable disease in 40.2%, progressive disease in 37.8%, and not evaluable in 13.4%. Median OS was 37.9 weeks. There was no difference in OS between the races (p=0.11). Conclusions: Patients with gynecologic cancers often enrolled into phase 1 trials later in the course of their disease. Most patients had stable disease and although low grade toxicities were common, very few patients experienced a DLT, suggesting that phase 1 trials are tolerable and can be considered earlier in a patient’s clinical course. This illustrates the ongoing necessity to implement strategies to overcome disparities among patients participating in early phase clinical trials, especially given the similar OS experience.
Impact of Sugammadex Versus Neostigmine Reversal on Postoperative Recovery Time in Patients With Obstructive Sleep Apnea Undergoing Bariatric Surgery: A Double-Blind, Randomized Controlled Trial
Authors: Ajetunmobi Olawale , Wong David , Perlas Anahi , Rajaleelan Wesley , Wang Stella , Huszti Ella , Jackson Timothy , Chung Frances , Wong Jean 
Published: June 2024

BACKGROUND:
Residual neuromuscular blockade can be associated with serious postoperative complications. Sugammadex is a newer neuromuscular blocking drug (NMBD) reversal agent that rapidly and completely reverses rocuronium. Whether sugammadex has any advantages over neostigmine in morbidly obese patients with obstructive sleep apnea (OSA) is unclear. We investigated whether sugammadex would reduce discharge time from the operating room (OR) compared with neostigmine in morbidly obese patients with OSA undergoing bariatric surgery.

METHODS:
This was a prospective, double-blinded randomized controlled superiority trial with 2 parallel groups. Patients were randomized 1:1 into reversal of NMBD with sugammadex or neostigmine. Our inclusion criteria were morbidly obese adult patients with OSA undergoing elective bariatric surgery under general anesthesia. Our exclusion criteria were allergy to rocuronium, sugammadex or neostigmine, malignant hyperthermia, hepatic or renal insufficiency, neuromuscular diseases, and an inability to give consent. The primary outcome was the time from administration of the NMBD reversal agent to discharge from the OR. Secondary outcomes included the time from administration of the NMBD reversal agent to the time the patient opened eyes to command, and the time to extubation. The Mann-Whitney test was used to compare the outcomes between treatment groups.

RESULTS:
We randomized 120 patients into 2 groups of 60 patients. Overall median body mass index (BMI) was 48.1 kg/m2 ([interquartile range, IQR]) [43.0–53.5]. The time from drug administration to discharge from OR was 13.0 minutes [10.0–17.0] in the sugammadex group and 13.5 minutes [11.0–18.3] in the neostigmine group (P = .27). The treatment effect estimate with a bootstrapped 95% confidence interval [CI] for time from admission to discharge from OR was −0.5 [−2.5 to 3]. No differences were observed in postoperative complications and other secondary outcomes.

CONCLUSIONS:
No difference was observed in OR discharge time in morbidly obese patients with OSA when sugammadex was administered instead of neostigmine.
Expanding Black and Indigenous Ecologies
Authors: Etherington Bonnie , Kumavie Delali 
Published: June 2024

Abstract
This issue navigates the intersections of Black and Indigenous ecologies. Colonial epistemologies still marginalize Black and Indigenous peoples in discussions about ecologies: they neglect Black and Indigenous peoples’ disproportionate environmental dispossession and the effects of environmental racism while “naturalizing” Black and Indigenous peoples as closer to the natural environment. The contributions to this issue draw on convergences between environmental inequality, sonic ecologies, and the legacies of colonialism to shape ongoing conversations. The issue traces historical as well as contemporary relationships and attends to the linkages and disruptions at work in Black and Indigenous ecologies, especially in the midst of climate change, which continues to affect those who are least responsible for the planet’s degradation. The articles in this issue make visible entwined histories in Black and Indigenous ecologies, as well as histories of oppression, that may trouble territorial boundaries and expand relationalities.
Sinophone Geopolitics and Postcolonial Materiality in Cold War Borneo
Authors: Liew Zhou Hau 
Published: June 2024

Abstract
This essay reads the Taiwanese Malaysian author Chang Kuei-hsing’s 1998 novel Elephant Herd from an ecological perspective. A novel about the Sarawak communist insurgency (1963–90)—an important but underrepresented conflict during the Cold War in Asia—Elephant Herd reappraises the legacies of this conflict through its ecological impact on the Bornean landscape and peoples. It critiques existing historical recollections of this period, which take the perspectives of either the colonial British government and its subsequent Malaysian inheritors or the largely ethnic Chinese leftist insurgents who sought to establish an independent Borneo state. The novel argues for a postcolonial remapping of Borneo beyond colonial statecraft and Cold War geopolitics in this contested territory, which are narrated through Chinese civilizational and Malay and British national narratives of place. It does so by staging a transformation of the settler Sinophone subject in Borneo, manifesting encounters in the Borneo rainforest that reveal the Indigenous experience of this insurgency and the cost of state-making projects in Borneo through environmental ruins such as elephant tusks. The novel concludes by proposing a postcolonial Bornean identity that begins from the perspective of the Indigenous Iban people, whose voices reframe the Sinophone narrator’s assumptions about land, history, and place beyond a settler point of view.
Endovascular Treatment of Spetzler-Martin Grade III Arteriovenous Malformations: A Single-Center 12 years' Experience Stratified by the Spetzler-Martin Modified Scale
Authors: de Oliveira Souza Natália Vasconcellos , Lamiraux Tabata , Vencato da Silva Felipe , Lima Vinicius Moreira , Rouchaud Aymeric , Saleme Suzana , Mounayer Charbel 
Published: June 2024

BACKGROUND AND OBJECTIVES:
Limited evidence exists for endovascular first-line treatment of Spetzler-Martin (SM) grade III brain arteriovenous malformations (AVMs). In this article, we sought to evaluate advanced endovascular techniques for treating SM III AVMs across different sizes, eloquence, and patterns of venous drainage.

METHODS:
Data from AVMs SM III treated between January 2010 and January 2022 were collected: size (S), eloquence (E), drainage (V), angioarchitecture features (arterial and venous aneurysms, venous drainage, and venous stenosis), treatment strategy (single arterial, double arterial, venous, both arterial and venous, and transvenous endovascular embolization with selective temporary flow arrest [TFATVE]), neoadjuvant treatment, and number of previous embolization sessions. AVMs were classified according to the modified SM grade as follows: small (S1V1E1/III-), medium/deep (S2V1E0/III), medium/eloquent (S2V0E1/III+), and large (S3V0E0). Treatment complications (hemorrhagic and ischemic), clinical discharge and 6-month outcomes (modified Rankin Scale 0-2, mRS), and angiographic occlusion rates were recorded.

RESULTS:
A total of 91 AVMs (62.6% ruptured, 72.5% S1V1E1, 7% S2V1E0, 19.7% S2V0E1, and 0% S3V0E0) in 91 patients (mean age 37 ± 15.8 years) were included. Treatment techniques included single arterial approach (28.6%), double arterial technique (30.8%), single venous strategy (9.9%), TFATVE (10.9%), and arterial and venous combined (19.8%). The angiographic occlusion rate was 91.2% (90.9% S1V1E1, 100% S2V1E0, and 88.9% S2V0E1) for all techniques, and 100% for the transvenous technique, isolated or combined with transarterial embolization. Minor complication (mRS 0-2), major complication (mRS >2), and mortality rate were 16.5%, 2.2%, and 3.4%, respectively. Overall, treatment morbimortality (mRS >2) was 3% (2/66) for S1V1E1, 0% for S2V1E0, and 16.7% (3/18) for S2V0E1.

CONCLUSION:
Although morbidity is non-negligible, endovascular treatment of SM grade III lesions with advanced techniques offers up to 100% rates of cure, which is of high interest, especially for ruptured deep-seated eloquent AVMs with high reruptured rates, and less amenable to microsurgery techniques.
A silver lining: did COVID-19 accelerate the road to gender equality?
Authors: Atherton Andrew 
Published: June 2024

Background/Aims As part of a larger study on gender inequality in the NHS, this study examined the impact of the COVID-19 pandemic on gender equality in NHS leadership. The aim was to investigate whether the pandemic facilitated conditions that better enabled workplace promotions for female leaders. Methods A qualitative modified grounded theory approach was used to study the perspectives of NHS leaders on issues impacting gender equality and career opportunities for women. The research sample consisted of 11 senior NHS managers. Data were collected using a questionnaire and in-depth interviews. Thematic analysis was used to identify key themes. Results The immediacy of the pandemic created critical job assignments which enabled female leaders to demonstrate their ability to perform in complex operational situations. The pandemic promoted cultural changes that influenced new ways of working which were seen as more suited to the needs of female employees, such as remote working or working part time. Conclusions The study challenges the ethos of presenteeism which exists in the NHS and highlights how the pandemic presented opportunities to overcome some of the barriers to advancement for female leaders. The normalisation of new ways of working, opportunities to gain operational experience and new methods of networking are all factors that could help aspiring female executives.
Adenosine, lidocaine, and magnesium therapy augments joint tissue healing following experimental anterior cruciate ligament rupture and reconstruction
Authors: Morris Jodie L. , Letson Hayley L. , McEwen Peter C. , Dobson Geoffrey P. 
Published: June 2024

AimsAdenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.MethodsMale (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.ResultsDespite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased.ConclusionAt 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials.Cite this article: Bone Joint Res 2024;13(6):279–293.
Non-typhoidal Salmonella contributes to gastrointestinal infections in Morogoro: Evidence from patients attending Morogoro regional referral hospital in Tanzania
Authors: Cuco Anacleta , Mkupasi Ernatus , Mzula Alexanda , Mdegela Robinson 
Published: June 2024

Introduction
Salmonella is one of the most common causes of food-borne outbreaks and infection worldwide. Non-typhoidal Salmonella (NTS) infections are common and remain a significant public health problem among important bacterial foodborne diseases. The current study aimed to establish the Non typhoidal Salmonella infection and antimicrobial resistance status among selected patients at Morogoro Regional Referral Hospital (MRRH), Morogoro Region, Tanzania, to inform clinical care management and public health interventions.

Methodology
A cross-sectional study was conducted using medical records and samples were collected from hospitalised and outpatients between October and December 2021. A total of 153 participants were enrolled in the study and 132 consented to being sampled. The collected samples were analysed using standard microbiological techniques. The isolates were subjected to molecular genotyping, where Polymerase Chain Reaction (PCR) was performed targeting the 16S rDNA gene. PCR products were then submitted for sequencing to establish phylogenetic relatedness. Antimicrobial susceptibility testing and resistance genes screening were also conducted.

Results
The phylogenetic analysis identified two Salmonella serovars; Salmonella Enteritidis and Salmonella Typhimurium. The isolates were from four adults and seven children patients. The isolates were tested against six antimicrobial agents: tetracycline, trimethoprim, gentamycin, ciprofloxacin, ampicillin and cefotaxime. Further antimicrobial assays were performed by screening 10 antimicrobial resistance genes using PCR. Overall, the highest resistance was observed in ampicillin (100%), whereas the lowest resistance was recorded for ciprofloxacin and gentamicin (9.1%). In addition, four (36.4%) of the isolates were resistant to cefotaxime and three (27.3%) to tetracycline and trimethoprim. The isolates also exhibit the presence of resistance genes for sulfamethoxazole 1&2, tetracycline (tet) A&B, Beta-lactamase CTXM, Beta-lactamase TEM, Beta-lactamase SHV, Gentamycine, Acra and acc3-1 in different occurrences. The overall prevalence of Salmonella species in Morogoro region was 8.3% (11/132) with Salmonella Enteritidis and Salmonella Typhimurium being the only serovars detected from adults and children stool samples.

Conclusion
Our investigation showed that both children and adults had been exposed to Salmonella spp. However, the occurrence of NTS was higher in children (5.3% (7/132) compared to adults (3.0% (4/132). To stop zoonotic infections and the development of antimicrobial resistance in the community, this calls for Infection Prevention and Control (IPC) and stewardship programmes on rational use of antimicrobials in both health facilities and at the community level.