bluuebunny/crossref_metadata_2025 huggingface dataset:
Surgical margin status outcome of intraoperative indocyanine green fluorescence-guided laparoscopic hepatectomy in liver malignancy: a systematic review and meta-analysis
Authors: Tangsirapat Vorapatu , Kengsakul Malika , Udomkarnjananun Suwasin , Sookpotarom Paiboon , Rattanasakalwong Mati , Nuchanatanon Jantaluck , Kongon Panutchaya , Wongta Kitti
Published: June 2024

Background

Hepatectomy stands as a curative management for liver cancer. The critical factor for minimizing recurrence rate and enhancing overall survival of liver malignancy is to attain a negative margin hepatic resection. Recently, Indocyanine green (ICG) fluorescence imaging has been proven implemental in aiding laparoscopic liver resection, enabling real-time tumor identification and precise liver segmentation. The purpose of this study is to conduct a systematic review and meta-analysis to ascertain whether ICG-guided laparoscopic hepatectomy yields a higher incidence of complete tumor eradication (R0) resections.

Methods

The search encompassed databases such as PubMed, Cochrane Library database, Scopus, ScienceDirect, and Ovid in April 2024, in strict adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies involving patients with malignant liver lesions who underwent ICG-guided laparoscopic hepatectomy and reported R0 resection outcomes were eligible for inclusion in this review.

Results

In a total of seven studies, involving 598 patients, were included in the meta-analysis. The ICG demonstrated a significantly elevated R0 resection rate compared to the non-ICG group [98.6% (359/364) vs. 93.1% (339/364), odds ratio (OR) = 3.76, 95% confidence intervals (CI) 1.45–9.51, P = 0.005]. Notably, no heterogeneity was observed (I2 = 0%, P = 0.5). However, the subtype analysis focusing on hepatocellular carcinoma [98.2% (165/168) vs. 93.6% (161/172), OR = 3.34, 95% CI 0.94–11.91, P = 0.06) and the evaluation of margin distance (4.96 ± 2.41 vs. 2.79 ± 1.92 millimeters, weighted mean difference = 1.26, 95% CI -1.8-4.32, P = 0.42) revealed no apparent differences. Additionally, the incidence of overall postoperative complications was comparable between both groups, 27.6% (66/239) in the ICG group and 25.4% (75/295) in the non-ICG group (OR = 0.96, 95% CI 0.53–1.76, P = 0.9). No disparities were identified in operative time, intraoperative blood loss, postoperative blood transfusion, and length of hospital stay after the surgery.

Conclusions

The implementation of ICG-guided laparoscopic hepatectomy can be undertaken with confidence, as it does not compromise either intraoperative or postoperative events. Furthermore, the ICG-guided approach is beneficial to achieving a complete eradication of the tumor during hepatic resection.

Trial registration

PROSPERO registration number CRD42023446440.
Impact of health insurance on the use of oral health services in the Peruvian population 2015–2019
Authors: Ruiz Jorge Alfredo Herrera , Pisfil-Benites Nilthon , Azañedo Diego , Hernández-Vásquez Akram
Published: June 2024

Background

The high treatment cost of oral diseases is a barrier for accessing oral health services (OHS), particularly in low-income countries. Therefore, this study aimed to evaluate the impact of health insurance on the use of OHS in the Peruvian population from 2015 to 2019.

Methods

We conducted a prospective, longitudinal study of secondary data using the National Household Survey (ENAHO) 2015–2019 panel databases, which collected information from the same participants during each of the five years. The dependent variable was the use of OHS in the three months prior to the survey (yes/no). The independent variable was health insurance affiliation (four years or less/all five years). Both were measured by survey questions. Generalized estimating equation (GEE) Poisson regression models with robust standard errors were used to estimate the relative risk (RR) associated with use of OHS.

Results

We included 4064 individuals distributed in 1847 households, who responded to the survey during each of the five years. The adjusted GEE model showed that those who had health insurance during all five years without interruption were more likely to attend OHS than those who had insurance for four years or less (adjusted relative risk [aRR]: 1.30; 95%CI: 1.13–1.50). In addition, we carried out a sensitivity analysis by recategorizing the independent variable into three categories (never/some years/ all five years), which also showed (aRR: 1.45; 95%CI: 1.11–1.89) that participants with health insurance during all five years were more likely to have used OHS than those who never had insurance.

Conclusion

Therefore, in the Peruvian context, health insurance affiliation was associated with greater use of OHS. The panel data used derives from a subsample of consecutive nationally representative samples, which may have led to a loss of representativeness. Furthermore, the data was collected between 2015 and 2019, prior to the onset of the COVID-19 pandemic, and insurance conditions may have changed.
Reasons and experience for patients with amyotrophic lateral sclerosis using traditional Chinese medicine: a CARE-TCM based mixed method study
Authors: Jia Qiuyang , Song Yuebo , Zhang Chi , Li Mingxuan , Feng Luda , Sugimoto Kazuo , Zhang Xuebin , Liu Jia , Gao Ying
Published: June 2024

Background and aim

Traditional Chinese medicine (TCM) is widely used by patients with amyotrophic lateral sclerosis (ALS). However, their reasons and experience in using TCM have received insufficient attention. Therefore, we conducted a mixed method study to gain insights into this issue.

Materials and methods

This study was conducted on the basis of the China Amyotrophic Lateral Sclerosis Registry of Patients with Traditional Chinese Medicine (CARE-TCM). Data were collected from Dongzhimen Hospital through a mixed method approach, including a questionnaire and a semi-structured interview. Patients with ALS who were using TCM when they were initially registered with CARE-TCM and who had been followed-up for over six months were recruited. The questionnaires’ outcomes were statistically outlined, and the interview transcripts were thematically analysed to identify themes and sub-themes.

Results

Fifty-two and sixteen patients were included in the questionnaire and semi-structured interview groups, respectively. Patients used TCM with the hope of regulating their body holistically to improve nonmotor symptoms and quality of life (QOL). Those who recognised TCM as ineffective tended to discontinue it after a three-month trial period. Although quality was a major concern, herbal medicine (HM) was the most frequently used modality among all participants (n = 52), with the majority (n = 44, 84.6%) continuing to use it. Patients emphasised in-person consultations as a crucial part of TCM treatment. However, the disability caused by disease often made this interaction unattainable.

Conclusion

Nonmotor symptoms and QOL hold substantial importance for patients with ALS using TCM. HM is a more suitable modality than other TCM treatment modalities, but patients are facing challenges in seeking HM treatment. It is necessary to promote the implementation of hierarchical diagnosis and treatment, thus making TCM more accessible.

Trial registration

ClinicalTrials.gov identifier: NCT04885374 (registered on May 13, 2021).
The role of dog therapy in clinical recovery and improving quality of life: a randomized, controlled trial
Authors: Mittly Veronika , Fáy Veronika , Dankovics Natália , Pál Vanda , Purebl György
Published: June 2024

Background

Any illness places a significant burden on patients, including deterioration in quality of life. Animal assisted therapy may be helpful in the rehabilitation process and in the treatment of patients to alleviate this phenomenon.

Methods

A randomized, controlled research was conducted in 2019 and 2020 in a rehabilitation center in Budapest. In our study, the control and experimental groups received the same therapy, but the rehabilitation treatment of the intervention group was complemented by dog therapy. Patients were evaluated by means of the short form Beck Depression Inventory, State-Trait Anxiety Inventory, Illness Intrusiveness Ratings Scale, Visual Analog Scale for pain and the WHO-5 Well-being Index. For statistical analysis paired T-test and ANCOVA was performed.

Results

58 participants in both groups took part in the research. Results confirm that both groups showed statistically significant improvement in all outcome measures, except for depression symptoms in dog therapy group. Quality of life of the participants improved significantly, their pain and anxiety levels were significantly reduced, they felt significantly less burdened by the disease in their daily lives. Therapeutic-dog sessions had a large effect on patients’ quality of life and anxiety.

Conclusions

There is a strong case for animal assisted therapy as a complementary therapy in the rehabilitation program, and it is proposed that consideration should be given to the application of this method on a larger scale within health care. The study was retrospectively registered at ISRCTN Registry (registration number: ISRCTN10208787) on 15/03/2022.
Targeted silencing of SOCS1 by DNMT1 promotes stemness of human liver cancer stem-like cells
Authors: Lou Lei , Deng Tingyun , Yuan Qing , Wang Lianghou , Wang Zhi , Li Xiang
Published: June 2024

Background

Human liver cancer stem-like cells (HLCSLCs) are widely acknowledged as significant factors in the recurrence and eradication of hepatocellular carcinoma (HCC). The sustenance of HLCSLCs’ stemness is hypothesized to be intricately linked to the epigenetic process of DNA methylation modification of genes associated with anticancer properties. The present study aimed to elucidate the stemness-maintaining mechanism of HLCSLCs and provide a novel idea for the clearance of HLCSLCs.

Methods

The clinical relevance of DNMT1 and SOCS1 in hepatocellular carcinoma (HCC) patients was evaluated through the GEO and TCGA databases. Cellular immunofluorescence assay, methylation-specific PCR, chromatin immunoprecipitation were conducted to explore the expression of DNMT1 and SOCS1 and the regulatory relationship between them in HLCSLCs. Spheroid formation, soft agar colony formation, expression of stemness-associated molecules, and tumorigenicity of xenograft in nude mice were used to evaluate the stemness of HLCSLCs.

Results

The current analysis revealed a significant upregulation of DNMT1 and downregulation of SOCS1 in HCC tumor tissues compared to adjacent normal liver tissues. Furthermore, patients exhibiting an elevated DNMT1 expression or a reduced SOCS1 expression had low survival. This study illustrated the pronounced expression and activity of DNMT1 in HLCSLCs, which effectively targeted the promoter region of SOCS1 and induced hypermethylation, consequently suppressing the expression of SOCS1. Notably, the stemness of HLCSLCs was reduced upon treatment with DNMT1 inhibitors in a concentration-dependent manner. Additionally, the overexpression of SOCS1 in HLCSLCs significantly mitigated their stemness. The knockdown of SOCS1 expression reversed the effect of DNMT1 inhibitor on the stemness of HLCSLCs. DNMT1 directly binds to the SOCS1 promoter. In vivo, DNMT1 inhibitors suppressed SOCS1 expression and inhibited the growth of xenograft.

Conclusion

DNMT1 targets the promoter region of SOCS1, induces hypermethylation of its CpG islands, and silences its expression, thereby promoting the stemness of HLCSLCs.
Therapeutic efficacy and safety of artemether-lumefantrine for uncomplicated Plasmodium falciparum malaria treatment in Metehara, Central-east Ethiopia
Authors: Tesfaye Mahelet , Assefa Ashenafi , Hailgiorgis Henok , Gidey Bokretsion , Mohammed Hussein , Tollera Getachew , Tasew Geremew , Assefa Gudissa , Bekele Worku , Mamo Hassen
Published: June 2024

Background

Malaria remains a major global health problem although there was a remarkable achievement between 2000 and 2015. Malaria drug resistance, along with several other factors, presents a significant challenge to malaria control and elimination efforts. Numerous countries in sub-Saharan Africa have documented the presence of confirmed or potential markers of partial resistance against artemisinin, the drug of choice for the treatment of uncomplicated Plasmodium falciparum malaria. The World Health Organization (WHO) recommends regular surveillance of artemisinin therapeutic efficacy to inform policy decisions.

Methods

This study aimed to evaluate the therapeutic efficacy of artemether-lumefantrine (AL), which is the first-line treatment for uncomplicated P. falciparum malaria in Ethiopia since 2004. Using a single-arm prospective evaluation design, the study assessed the clinical and parasitological responses of patients with uncomplicated P. falciparum malaria in Metehara Health Centre, central-east Ethiopia. Out of 2332 malaria suspects (1187 males, 1145 females) screened, 80 (50 males, 30 females) were enrolled, followed up for 28 days, and 73 (44 males, 29 females) completed the follow up. The study was conducted and data was analysed by employing the per-protocol and Kaplan–Meier analyses following the WHO Malaria Therapeutic Efficacy Evaluation Guidelines 2009.

Results

The results indicated rapid parasite clearance and resolution of clinical symptoms, with all patients achieving complete recovery from asexual parasitaemia and fever by day (D) 3. The prevalence of gametocytes decreased from 6.3% on D0 to 2.5% on D2, D3, D7, and ultimately achieving complete clearance afterward.

Conclusion

The overall cure rate for AL treatment was 100%, demonstrating its high efficacy in effectively eliminating malaria parasites in patients. No serious adverse events related to AL treatment were reported during the study, suggesting its safety and tolerability among the participants. These findings confirm that AL remains a highly efficacious treatment for uncomplicated P. falciparum malaria in the study site after 20 years of its introduction in Ethiopia.
Therapeutic potential of exosomes derived from mesenchymal stem cells for treatment of systemic lupus erythematosus
Authors: Samavati Shima Famil , Yarani Reza , Kiani Sara , HoseinKhani Zohreh , Mehrabi Masomeh , Levitte Steven , Primavera Rosita , Chetty Shashank , Thakor Avnesh S. , Mansouri Kamran
Published: June 2024

Autoimmune diseases are caused by an imbalance in the immune system, producing autoantibodies that cause inflammation leading to tissue damage and organ dysfunction. Systemic Lupus Erythematosus (SLE) is one of the most common autoimmune diseases and a major contributor to patient morbidity and mortality. Although many drugs manage the disease, curative therapy remains elusive, and current treatment regimens have substantial side effects. Recently, the therapeutic potential of exosomes has been extensively studied, and novel evidence has been demonstrated. A direct relationship between exosome contents and their ability to regulate the immune system, inflammation, and angiogenesis. The unique properties of extracellular vesicles, such as biomolecule transportation, biodegradability, and stability, make exosomes a promising treatment candidate for autoimmune diseases, particularly SLE. This review summarizes the structural features of exosomes, the isolation/purification/quantification method, their origin, effect, immune regulation, a critical consideration for selecting an appropriate source, and their therapeutic mechanisms in SLE.
Association between metabolic score for insulin resistance and clinical outcomes: insights from the Tehran lipid and glucose study
Authors: Tamehri Zadeh Seyyed Saeed , Cheraghloo Neda , Masrouri Soroush , Esmaeili Farzad , Azizi Fereidoun , Hadaegh Farzad
Published: June 2024

Background

We aimed to assess the relationship between Metabolic Score for Insulin Resistance (METS-IR) and the incidence of coronary heart disease (CHD), stroke, mortality, diabetes, hypertension, and chronic kidney disease (CKD) in a population from the Middle East and North Africa (MENA) region.

Method

Individuals aged ≥ 20 years were enrolled. Cox proportional hazards regression models were applied to assess the association between METS-IR and incident CHD, stroke, all-cause mortality, diabetes, hypertension, and CKD.

Results

Over a median follow-up period of 9–18 years, 1080 (10.6%), 267 (2.6%), 1022 (9.6%), 1382 (16.4%), 2994 (58.5%), and 2002 (23.0%) CHD, stroke, all-cause mortality, diabetes, hypertension, and CKD events occurred, respectively. Compared to the lowest quartile (reference), the hazard ratios (HR) associated with the highest quartile of METS-IR were 1.527 (95% confidence interval [CI]: 1.208–1.930, P for trend 0.001), 1.393 (0.865–2.243, > 0.05), 0.841 (0.682–1.038, > 0.05), 3.277 (2.645–4.060, < 0.001), 1.969 (1.752–2.214, < 0.001), and 1.020 (0.874–1.191, > 0.05) for CHD, stroke, all-cause mortality, diabetes, hypertension, and CKD, respectively. METS-IR, as a continuous variable, was significantly associated with the risk of incident CHD [HR, 95% CI: 1.106, 1.034–1.184], diabetes [1.524, 1.438–1.616], and hypertension [1.321, 1.265–1.380]. These associations were also independent of metabolic syndrome (METS) and remained unchanged in a subgroup of individuals without METS and/or diabetes.

Conclusions

Increasing levels of METS-IR were significantly associated with a greater risk of incident CHD, diabetes, and hypertension; therefore, this index can be a useful tool for capturing the risk of these clinical outcomes.
Iatrogenic non-coronary leaflet perforation as a complication after robotic mitral valve repair
Authors: Kalangos Afksendiyos , Zorman Yilmaz , Güler Emel Celiker , Shatelen Nataliia
Published: June 2024

Iatrogenic aortic regurgitation secondary to leaflet injury is a rare complication of mitral valve surgery. For the first time, we report a patient who had progressive aortic regurgitation due to non-coronary leaflet perforation after robotic mitral valve repair and required aortic valve repair 18 months after this initial surgery. As in our case, aortic regurgitation after mitral valve surgery may remain undiagnosed on intraoperative transesophageal echocardiography or undetected until the patient’s discharge due to gradual enlargement of very small perforations over the postoperative course.
The history of short-tailed whip scorpions: changes in body size and flagellum shape in Schizomida
Authors: Belojević Jelena , Mortier Meghana S. , Oberweiser Morgan M. , Braig Florian , Haug Joachim T. , Haug Carolin
Published: June 2024

Representatives of Schizomida, known as short-tailed whip scorpions, are an understudied group within Megoperculata. They are found subterraneanly in tropical and sub-tropical regions. They lack eyes, have superior mobility, and possess a flagellum which is relevant to their mating, but in general little is known about their general biology. Fossil representatives of Schizomida from a variety of time periods are available for study. Using 23 fossil specimens (14 of which are described here for the first time) and 86 extant individuals from the literature, changes in both body size and flagella shape in Schizomida were compared over time. Measurements of prosoma length and leg length were used as a proxy for body size, and a comparative size analysis was carried out. Individuals from the Cretaceous period were found to be significantly smaller than extant individuals, contrary to our expectations. For flagellum shape, images were used to create reconstructions, which were then analysed using an elliptic Fourier analysis followed by a principal component analysis. The morphological diversity of the male flagellum shape was found to have decreased between the Cretaceous and modern fauna. We discuss potential explanations for our findings, although a greater understanding of the general biology of Schizomida is required to properly interpret our results.
A growth selection system for sucrose synthases (SuSy): design and test
Authors: Bidart Gonzalo N. , Hyeuk Se , Alter Tobias Benedikt , Yang Lei , Welner Ditte Hededam
Published: June 2024

High throughput screening (HTS) methods of enzyme variants are essential for the development of robust biocatalysts suited for low impact, industrial scale, biobased synthesis of a myriad of compounds. However, for the majority of enzyme classes, current screening methods have limited throughput, or need expensive substrates in combination with sophisticated setups. Here, we present a straightforward, high throughput selection system that couples sucrose synthase activity to growth. Enabling high throughput screening of this enzyme class holds the potential to facilitate the creation of robust variants, which in turn can significantly impact the future of cost effective industrial glycosylation.
Quantitative gray matter volumetric analysis in schizophrenia: investigating the risk of violent behaviors through structural MRI
Authors: Li Yingna , Liang Wenzhou , Zhao Liying
Published: June 2024

Background

Extensive research has been dedicated to exploring the neurobiological underpinnings of schizophrenia, yet there has been comparatively less emphasis on investigating specific markers associated with violent behaviors within this condition.

Aim of the study

This study aimed to compare gray matter thickness and volume and investigate clinical markers for assessing violence risk in schizophrenia.

Results

We enrolled a total of 36 participants, comprising 19 patients with a documented history of violent behaviors in schizophrenia and 17 patients with no such history. Schizophrenia patients with a history of violence exhibited a significant reduction in cortical thickness in the left caudal-middle-frontal gyrus (2.540 ± 0.146 mm) compared to those without such history (2.757 ± 0.126 mm) (P = 0.0301). Similarly, the cortical volume in the right middle temporal gyrus was decreased in patients with a history of violence (15.579 ± 8.790 mm3) compared to non-violent patients (29.941 ± 13.585 mm3) (P = 0.0071). ROC analysis demonstrated promising diagnostic efficiency, with an AUC of 0.876 for left caudal-middle-frontal gyrus thickness (P = 0.000) and 0.794 for right middle temporal gyrus volume (P = 0.003).

Conclusions

Our findings highlight brain cortical assessments as potential diagnostic biomarkers to identify individuals at risk of violent behavior within the schizophrenia population.
The comovements of tail risks in time and frequency domains: evidence from US and emerging Asian stock markets
Authors: Baba Boubekeur
Published: June 2024

The study applies the wavelet local multiple correlations to investigate the level of comovements among the tail risks of US and emerging Asian stock markets in both time and frequency domains. Through this empirical investigation, we address the question of how the transmission of tail risk across the concerned stock markets is changing over specific timescales, varying from short term to long term. Empirical results from the multivariate time–frequency correlations show that the comovements of tail risks are distinctively higher during periods of economic and political turmoil in the short term. The multivariate long-term comovements are highly stable and extremely strong which can be taken as evidence of long-term integration. In contrast, the bivariate time–frequency correlations are remarkably weaker in the short term not only during periods of crises but over most of the sample period. The results of the bivariate analysis also highlight the instability of the long-term pairwise correlations of the tail risks, showing that it is susceptible to sudden changes, which indicates that the tail risks of the US and emerging Asian stock markets are actually not completely integrated in the long term. This finding also implies that the tail risks of US and emerging Asian stock markets are nonlinearly connected in the long term.
Two-dimensional transthoracic measure of mitral annulus in mitral valve prolapse and moderate to severe regurgitation: a method comparison analysis with three-dimensional transesophageal echocardiography
Authors: Berthelot-Richer Maxime , Vakulenko Halyna Viktorivna , Calleja Anna , Woo Anna , Thavendiranathan Paaladinesh , Poulin Frédéric
Published: June 2024

Background

Mitral annulus (MA) area is derived during transthoracic echocardiography (TTE) assuming of a circular shape using the MA diameter from the apical 4 chamber (A4c) view. Since the MA is not a circular structure, we hypothesized that an elliptical model using parasternal long-axis (PLAX) and apical 2 chamber (A2c) view measured MA diameters would have better agreement with 3-dimensional transesophageal echocardiography (3D TEE) measured MA in degenerative mitral valve disease (DMVD).

Methods

Seventy-six patients with moderate-to-severe DMVD had 2D TTE and 3D TEE performed. MA area was measured retrospectively using semi-automatic modeling of 3D data (3D TEEsa) and considered as the reference method. MA diameters were measured using different 2D TTE views. MA area was calculated using assumptions of a circular or an elliptical shape. 2D TTE derived and 3D TEEsa. MA areas were compared using linear regression and Bland-Altman analysis.

Results

The median MA area measured at 3D TEEsa was 1,386 (1,293–1,673) mm2. With 2D TTE, the circular model using A4c view diameter resulted in a small systematic underestimation of MA area (6%), while the elliptical model using PLAX and A2c diameters resulted in 25% systematic underestimation. The standard deviations of the distributions of inter-method differences were wide for all 2D TTE methods (265–289 mm2) when compared to 3D TEEsa, indicating imprecision.

Conclusions

When compared with 3D TEEsa modeling of the MA as the reference, the assumption of a circular shape using A4c TTE view diameter was the method with the least systematic error to assess MA area in DMVD and moderate to severe regurgitation.
A phase 3 global study of telisotuzumab vedotin versus docetaxel in previously treated patients with c-Met 0verexpressing, EGFR wildtype, locally advanced/metastatic nonsquamous NSCLC (TeliMET NSCLC-01).
Authors: Lu Shun , Goldman Jonathan W. , TANIZAKI JUNKO , Akamatsu Hiroaki , Xia Summer , Ratajczak Christine , Li Martha , Bolotin Ellen , Seraj Jabed , Lugini Antonio
Published: June 2024

TPS8656

Background: Non-small cell lung cancer (NSCLC) encompasses over two-thirds of lung cancer diagnoses, most presenting as advanced disease. c-Met (MET protein) is overexpressed in NSCLC. In this study, we investigate telisotuzumab vedotin (Teliso-V), a first-in-class antibody-drug conjugate composed of a c-Met–targeting antibody (telisotuzumab) and a microtubule polymerization inhibitor (cytotoxin monomethyl auristatin E). Interim efficacy analysis of the Phase 2 LUMINOSITY study (NCT03539536) of Teliso-V monotherapy showed an objective response rate (ORR) of 37% (95% CI: 24–51) in previously treated patients (pts) with c-Met overexpressing epidermal growth factor receptor (EGFR) wildtype (WT) nonsquamous NSCLC and 52% (95% CI: 31–73) in the high c-Met overexpressing group (Camidge DR et al. J Clin Oncol. 2022;40(16_suppl):9016). Methods: This randomized, open-label, global Phase 3 study (NCT04928846) evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of Teliso-V monotherapy compared with docetaxel in pts with locally advanced/metastatic c-Met overexpressing EGFR WT nonsquamous NSCLC who have progressed on prior therapy. Enrollment began in May 2022. To be eligible across global sites, pts must be ≥18 years old with c-Met overexpressing (ie, ≥25% tumor cells at 3+ intensity by IHC assay [anti-MET clone SP44; Roche Tissue Diagnostics]) locally advanced/metastatic EGFR WT NSCLC, with ECOG score ≤1. Pts must have progressed on at least one prior line of therapy, which can include no more than one line of prior chemotherapy, and must be naïve to c-Met–targeted antibodies and docetaxel. Target enrollment is 698 pts. Pts will be randomized 1:1 to Teliso-V (1.9 mg/kg every 2 weeks) and docetaxel (control, 75 mg/m2 every 3 weeks). Treatment continues until disease progression or discontinuation criteria are met. Co-primary endpoints are progression-free survival by independent central review and overall survival. Secondary endpoints include ORR, duration of response, and patient-reported outcomes. Safety, adverse events (AEs), drug discontinuation or dosing modification due to AEs, and tolerability will be assessed. Previously presented at the 2023 ESMO Congress, Final Publication Number: 1501TiP, Antonio Lugini et al. - Reused with permission. Clinical trial information: NCT04928846 .
Poly(ADP-Ribose) Polymerase Inhibitor Development: Promising Strategies to Move Beyond Approved Indications
Authors: Torrado Carlos , Plummer Ruth , Yap Timothy A.
Published: June 2024

Biomarker-based patient selection and rational combinations show promise in expanding the use of PARP inhibitors
Seven years of Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP): Rate of Acceptance and Variation of Diagnostic Approaches Across Different Continents
Authors: Williams Michelle D , Liu Zhiyan , Rossi Esther Diana , Agarwal Shipra , Ryška Aleš , Ghuzlan Abir Al , Bychkov Andrey , Baloch Zubair , Chernock Rebecca , Chiosea Simion L , Cipriani Nicole A , Erkilic Suna , Fridman Michael , Hang Jen-Fan , Harahap Agnes Stephanie , Jung Chan Kwon , Kakudo Kennichi , Khalil Moosa , Khanafshar Elham , Kumarasinghe Priyanthi , Lloyd Ricardo , Nguyen Truong Phan-Xuan , Ocal Idris Tolgay , Prasad Manju L , Pusztaszeri Marc , Rana Chanchal , Sadow Peter , Sajed Dipti P , Seethala Raja , Tallini Giovanni , Vuong Huy Gia , Yegen Gülçin , LiVolsi Virginia A , Nikiforov Yuri E
Published: June 2024

Context

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced as a new entity replacing the diagnosis of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (PTC). Significant variability in the incidence of NIFTP diagnosed in different world regions has been reported.

Objective

To investigate the rate of adoption of NIFTP, change in practice patterns, and uniformity in applying diagnostic criteria among pathologists practicing in different regions.

Methods

Two surveys distributed to pathologists of the International Endocrine Pathology Discussion Group with multiple-choice questions on NIFTP adoption into pathology practice and whole slide images of 5 tumors to collect information on nuclear score and diagnosis. Forty-eight endocrine pathologists, including 24 from North America, 8 from Europe, and 16 from Asia/Oceania completed the first survey and 38 the second survey.

Results

A 94% adoption rate of NIFTP by the pathologists was found. Yet, the frequency of rendering NIFTP diagnosis was significantly higher in North America than in other regions (P = .009). While the highest concordance was found in diagnosing lesions with mildly or well-developed PTC-like nuclei, there was significant variability in nuclear scoring and diagnosing NIFTP for tumors with moderate nuclear changes (nuclear score 2) (case 2, P < .05). Pathologists practicing in North America and Europe showed a tendency for lower thresholds for PTC-like nuclei and NIFTP than those practicing in Asia/Oceania.

Conclusion

Despite a high adoption rate of NIFTP across geographic regions, NIFTP is diagnosed more often by pathologists in North America. Significant differences remain in diagnosing intermediate PTC-like nuclei and respectively NIFTP, with more conservative nuclear scoring in Asia/Oceania, which may explain the geographic differences in NIFTP incidence.
Lower Independent Self-Care Readiness Persists Over Time in Teens With Type 1 Diabetes and Executive Function Challenges
Authors: Vitale Rebecca J , Tinsley Liane J , Volkening Lisa K , Laffel Lori M
Published: June 2024

Purpose

Management of type 1 diabetes is complex and benefits from adequate executive function (EF) (planning, organization, problem-solving). Teens with diabetes and executive dysfunction may have challenges with the acquisition of self-care skills.

Methods

Over 18 months, parents of teens with type 1 diabetes aged 13 to 17 completed the Diabetes Family Responsibility Questionnaire (DFRQ) and Readiness for Independent Self-Care Questionnaire (RISQ) every 6 months. Parents assessed teen EF, completing the Behavior Rating Inventory of Executive Function (BRIEF). T-score ≥60 defined EF challenges. EF, demographic, and diabetes treatment variables predicted RISQ score over time using longitudinal mixed modeling with false discovery rate adjustment.

Results

There were 169 teen participants (54% male) aged 15.9 ± 1.3 years, diabetes duration 8.4 ± 3.7 years, and A1c 8.6 ± 1.2%. About a third (31.4%) of teens had parent-reported BRIEF Global Executive Composite (GEC) scores ≥60. After adjusting for age, sex, and DFRQ, those with GEC <60 had a RISQ score 4.1 points higher than those with GEC ≥60, P = .016. Metacognition index (MI; adjusted for age,sex, and DFRQ) predicted RISQ while behavioral regulation index (adjusted for age, continuous glucose monitor use, DFRQ, and A1c) did not; those with MI <60 had a RISQ score 5.3 points higher than those with MI ≥60, P < .001. In all models, older teen age (P < .05) and less parental involvement (P < .001) predicted higher RISQ score.

Conclusion

EF skills, especially metacognition, appear important for the acquisition of self-care behaviors in teens with type 1 diabetes. Evaluating EF during adolescence may identify teens needing extra support during the transition process.
Glycodeoxycholic Acid Inhibits Primary Bile Acid Synthesis With Minor Effects on Glucose and Lipid Homeostasis in Humans
Authors: Meessen Emma C E , Majait Soumia , Ay Ümran , Olde Damink Steven W , Romijn Johannes A , Holst Jens J , Hartmann Bolette , Kuipers Folkert , Nieuwdorp Max , Schaap Frank G , Groen Albert K , Kemper E Marleen , Soeters Maarten R
Published: June 2024

Background

Bile acids play vital roles in control of lipid, glucose, and energy metabolism by activating Takeda G protein-coupled receptor 5 and Farnesoid X receptor, the latter promoting production of the endocrine-acting fibroblast growth factor 19 (FGF19). Short-term administration of single bile acids has been reported to enhance plasma levels of GLP-1 and to enhance energy expenditure. However, prolonged bile acid supplementation (eg, of chenodeoxycholic acid for gallstone dissolution) has been reported to have adverse effects.

Study design

In this proof-of-concept study, we assessed the safety and metabolic effects of oral glycine-conjugated deoxycholic acid (GDCA) administration at 10 mg/kg/day using regular and slow-release capsules (mimicking physiological bile acid release) over 30 days in 2 groups of each 10 healthy lean men, respectively.

Main findings

GDCA increased postprandial total bile acid and FGF19 concentrations while suppressing those of the primary bile acids chenodeoxycholic acid and cholic acid. Plasma levels of 7α-hydroxy-4-cholesten-3-one were reduced, indicating repressed hepatic bile acid synthesis. There were minimal effects on indices of lipid, glucose, and energy metabolism. No serious adverse events were reported during GDCA administration in either capsule types, although 50% of participants showed mild increases in plasma levels of liver transaminases and 80% (regular capsules) and 50% (slow-release capsules) of participants experienced gastrointestinal adverse events.

Conclusion

GDCA administration leads to elevated FGF19 levels and effectively inhibits primary bile acid synthesis, supporting therapy compliance and its effectiveness. However, effects on lipid, glucose, and energy metabolism were minimal, indicating that expanding the pool of this relatively hydrophobic bile acid does not impact energy metabolism in healthy subjects.
Settler Shock: Colonial Fetishism and the Disavowal of Violence in Contemporary Canada
Authors: Weiss Joseph
Published: June 2024

This article draws on an analysis of the consistent phenomenon of “settler shock”—the persistent invocations of surprise expressed by settler Canadians whenever there are reports of historical or ongoing violence against Indigenous Peoples—to articulate the dynamics of colonial fetishism and settler disavowal. It demonstrates how these expressions of shock are not, as they might appear, authentic responses to genuinely unknown events but rather are part of a system of discourses that conceal the violence of settler colonialism by erasing its continuities, displacing its violence into the past, and removing Indigenous subjects from the circle of “legitimate” citizens against whom military violence would be prohibited. In particular, it considers different forms of colonial disavowal—one that hinges on time, the other on political status—demonstrating how the fetishism of land as colonial property is the stabilizing force on which colonial disavowal rests. It ends by suggesting, however, that settler colonialism can never, in truth, be stabilized.
From Dazzle to Diesel
Authors: Bergère Clovis , Kraidy Marwan M.
Published: June 2024

The rise of Turkish television drama series—or dizi as they are known in Turkey—is one of the most notable media phenomena of the past decade in francophone West Africa, particularly Guinea. This is taking place at a time when Turkey has significantly ramped up its economic, political, and cultural investments in Africa, with countries such as Guinea, rich in natural resources and with geostrategic sea access, rapidly emerging as new targets for Turkey's outsized ambitions. This article asks what we can learn about the global circulation of Turkish modernity—a unique blend of tantalizing consumerism and piety conceptualized as “neo-Ottoman cool”—in francophone West Africa by analyzing the hugely popular dizi alongside public debates on Turkey's investments in energy, transportation, energy, culture, or construction. Drawing on Joseph Tonda's notion of éblouissement (dazzlement), it argues that Guineans, like other West Africans, encounter the dazzling images of Istanbul's rich and famous that permeate dizi in stark contrast with Turkish investments in floating power plants and public transport or the Turkish-built Abdul Hamid II Mosque in Bambeto, a popular quarter of Conakry. The article proposes the phrase dazzle-to-diesel to account for the constant oscillation between blinding power and toxic fumes that accompanies encounters with neo-Ottoman cool in West Africa.
Open Microsurgical Cerebral Aneurysm Treatment After Failed Endovascular Therapy: An Evaluation of Aneurysm Treatment Frequencies in All Neurovascular Centers Across Austria and the Czech Republic Over 20 Years
Authors: Griessenauer Christoph J. , Dodier Philippe , Stroh Nico H. , Mercea Petra A. , Bavinzski Gerhard , Dorfer Christian , Rössler Karl , Gruber Andreas , Gmeiner Matthias , Thomé Claudius , Leber Klaus A. , Wolfsberger Stefan , Baghban Mustafa , Al-Schameri Rahman , Kral Michael , Thakur Som , Lunzer Manuel , Popadic Branko , Sherif Camillo , Juráň Vilém , Smrčka Martin , Netuka David , Štekláčová Anna , Lipina Radim , Hrbáč Tomáš , Večeřa Zdeněk , Fiedler Jiří , Grubhoffer Marek , Hrabálek Lumír , Krahulík David , Koller Lukas , Kretschmer Thomas , Přibáň Vladimír , Mraček Jan , Sameš Martin , Hejčl Aleš , Klener Jan , Šroubek Jan , Petr Ondra
Published: June 2024

BACKGROUND AND OBJECTIVES:

Endovascular treatment of cerebral aneurysms has tremendously advanced over the past decades. Nevertheless, aneurysm residual and recurrence remain challenges after embolization. The objective of this study was to elucidate the portion of embolized aneurysms requiring open surgery and evaluate whether newer endovascular treatments have changed the need for open surgery after failed embolization.

METHODS:

All 15 cerebrovascular centers in Austria and the Czech Republic provided overall aneurysm treatment frequency data and retrospectively reviewed consecutive cerebral aneurysms treated with open surgical treatment after failure of embolization from 2000 to 2022. All endovascular modalities were included.

RESULTS:

On average, 1362 aneurysms were treated annually in the 2 countries. The incidence increased from 0.006% in 2005 to 0.008% in 2020 in the overall population. Open surgery after failed endovascular intervention was necessary in 128 aneurysms (0.8%), a proportion that remained constant over time. Subarachnoid hemorrhage was the initial presentation in 70.3% of aneurysms. The most common location was the anterior communicating artery region (40.6%), followed by the middle cerebral artery (25.0%). The median diameter was 6 mm (2-32). Initial endovascular treatment included coiling (107 aneurysms), balloon-assist (10), stent-assist (4), intrasaccular device (3), flow diversion (2), and others (2). Complete occlusion after initial embolization was recorded in 40.6%. Seventy-one percent of aneurysms were operated within 3 years after embolization. In 7%, the indication for surgery was (re-)rupture and, in 88.3%, reperfusion. Device removal was performed in 16.4%. Symptomatic intraoperative and postoperative complications occurred in 10.2%. Complete aneurysm occlusion after open surgery was achieved in 94%.

CONCLUSION:

Open surgery remains a rare indication for cerebral aneurysms after failed endovascular embolization even in the age of novel endovascular technology, such as flow diverters and intrasaccular devices. Regardless, it is mostly performed for ruptured aneurysms initially treated with primary coiling that are in the anterior circulation.
Λαϊκή πίστη και τελετουργίες για την Παναγία και τους αγίους στη Βοιωτία
Authors: Στούκης Γεώργιος
Published: June 2024

Η συγκεκριμένη διατριβή είναι μια λαογραφική μελέτη, που ανήκει στο πεδίο της θρησκευτικής Λαογραφίας. Συνδυάζει την αρχειακή και βιβλιογραφική έρευνα με την επιτόπια, και μελετά τις λαϊκές θρησκευτικές τελετουργίες που αναφέρονται στην Παναγία και τους αγίους, τόσο τους τοπικούς, όσο και τους οικουμενικά τιμώμενους, στην σύγχρονη Βοιωτία, με αναφορές και στη διαχρονική πορεία τους. Καλύπτει, επίσης, ένα βιβλιογραφικό κενό επειδή μέχρι τώρα από την έρευνα που έγινε εντοπίστηκαν πολλά δημοσιεύματα για επιμέρους ζητήματα σχετικά με την λαϊκή θρησκευτική πίστη και λατρεία στη Βοιωτία, αλλά δεν υπήρξε σύνθεση του διάσπαρτου αυτού υλικού. Εξετάζονται θέματα γύρω από τους ιερείς και τη θέση τους, τον κύκλο του χρόνου, τις θρησκευτικές παραδόσεις, την τοπική εκκλησία, τις αφιερωματικές πρακτικές, τις πράξεις για άμεση επαφή του ανθρώπου με το θείο, τα πανηγύρια, τις λατρευτικές-λειτουργικές πράξεις. Η μελέτη ολοκληρώνεται με τα συμπεράσματα, όπου γίνεται συγκεφαλαίωση των νέων δεδομένων που η διατριβή έφερε στο φως, και των νέων ερμηνευτικών στοιχείων που παρουσιάζει για τη λαϊκή λατρευτική παράδοση και την πίστη των Βοιωτών για την Παναγία και τους αγίους, ως συμβολή στην μελέτη της παραδοσιακής και της σύγχρονης λαϊκής θρησκευτικής συμπεριφοράς τους.
Case Report: Concomitant presence of two STIs in a male patient
Authors: Rusia Kaveri , Madke Bhushan , Kashikar Yash
Published: June 2024

Background The spirochaete Treponema pallidum subsp. pallidum, which causes the infectious disease syphilis, can be spread through sexual contact or perinatal transmission. In recent years, cases of syphilis have increased, especially among individuals engaging in behaviour that makes them more vulnerable (condomless sex and multiple sexual partners). Condylomata acuminata (external genital warts) is one of the most common viral sexually transmitted infections (STIs). Individuals who are behaviourally vulnerable are also highly prone to two or more STIs. Our case exemplifies the occurrence of two STIs in a young man who was behaviourally vulnerable to acquiring STIs. Case We report a case of a 21-year-old year old heterosexual man presenting with concomitant primary syphilis and genital warts. He presented with a painless genital ulcer and warty growths on his glans penis. Examination showed a painless indurated ulcer and multiple genital warts. Serology was positive for quantitative Venereal disease research laboratory test (1:16 titre). The patient was diagnosed with two concomitant STIs. He was treated as per the latest Centers for Disease Control and Prevention (CDC) guidelines for primary syphilis and podophyllin resin for genital warts. After four weeks, the genital ulcer showed complete healing and there was a significant reduction of genital warts. Conclusions Individuals with multiple sexual partners engaging in sexual activity without the use of prevention tools are at a greater chance of acquiring two or more STIs. To reduce concomitant transmission, preventive measures against genital ulcer diseases like syphilis, herpes, and chancroid, such as early identification and treatment, and condom distribution, must be strengthened as part of national STI prevention. Patients with two or more STIs should be followed regularly to assess the progress of infection and should be offered timely medical treatment.
Case Report: Sebaceous carcinoma of the eyelid
Authors: Bhawani Jayashree , Shukla Samarth , Acharya Sourya , Vagha Sunita , Jagtap Miheer
Published: June 2024

Sebaceous carcinoma is an extremely rare malignant disease and it is more aggressive when it occurs in the eyelids and orbit. It can mimic several benign lesions, resulting in diagnostic delay. We present a case of sebaceous carcinoma in a 50-year-old male who presented with complaints of swelling of the upper eyelid, which was followed by appearance of an ulcerative growth over the eyelid. Magnetic resonance imaging (MRI) reports showed an ulcerated mass in the left periorbital and orbital region appearing heterogeneously hyperintense. Fine needle aspiration cytology (FNAC) showed malignant epithelial differentiation which was followed by exenteration of the eyeball. Histopathology showed the rare diagnosis of sebaceous carcinoma. The disease has a poor prognosis as the entity is associated with increased morbidity and if not detected early it can metastasize to other organs which may be fatal sometimes.