bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic efficacy and safety results of 177Lu-PSMA therapy in metastatic castration-resistant prostate cancer patients: first experience of a developing South Asian Country
Authors: Parveen Azra , Fatima Arzoo , Fatima Ismat , Khan Irfan U. , Shahid Abubaker 
Published: July 2023

Objective
Metastatic castration resistant-prostate cancer (mCRPC) is deadly condition that remains incurable despite various therapies. Initial studies have shown promising results with Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA) therapy for advanced prostate cancer. However, most of the published efficacy and safety data is retrospective. The purpose of the study was to prospectively evaluate the therapeutic efficacy and safety results of 177Lu-PSMA therapy in mCRPC patients after 2 cycles.

Methods
Twenty-five patients of mCRPC, treated with standard care treatment were enrolled for 2 cycles of 177Lu-PSMA therapy. Prostate-specific antigen (PSA), Eastern Cooperative Oncology Group (ECOG) performance status, Visual Analogue Score (VAS) and Analgesic Quantification Scale (AQS) for efficacy and hemoglobin, total leukocyte, platelets and serum creatinine for toxicity were recorded pre and post-therapy. Paired sample t-test was used for statistical analysis.

Results
Treated patients with mean PSA level of 157 ng/ml received mean dose of 6.84 GBq of 177Lu-PSMA. For PSA, partial response (PR) was seen in 11/25 (44%), stable disease (SD) in 8/25 (32%) and progressive disease (PD) in 6/25 (24%) patients. Grade 1 and 2 hemoglobin toxicity was seen in 5/25 (20%) and 6/25 (24%) patients respectively. No patient developed grade 3 or 4 bone marrow toxicities. Grade 1 and 2 nephrotoxicity was seen in 1 patient each. Statistically significant difference was seen in ECOG, VAS and AQS scores (P < 0.001). No significant nephrotoxicity was observed (P = 0.558).

Conclusion
Efficacy and safety of 177Lu-PSMA therapy after 2 cycles have shown significant PSA response and pain palliation in heavily pretreated mCRPC patients.
Pediatric Aerodigestive Medicine: Advancing Collaborative Care for Children With Oropharyngeal Dysphagia
Authors: Krasaelap Amornluck , Duncan Daniel R. , Sabe Ramy M. M. , Bhardwaj Vrinda , Lerner Diana G. , Gold Benjamin D. , Boesch Richard Paul , Faure Christophe , von Allmen Daniel , Williams Dana , Chiou Eric , DeBoer Emily , Hysinger Erik , Maybee Jennifer , Khlevner Julie , Larson Kara , Morris Kimberly , Jalali Lauren , McSweeney Maireade , Brigger Matthew T. , Greifer Melanie , Rutter Michael , Williams Nina , Subramanyan Ram Kumar , Ryan Matthew J. , Acra Sari , Pentiuk Scott , Friedlander Joel , Sobol Steven E. , Kaul Ajay , Dorfman Lev , Darbari Anil , Prager Jeremy D. , Rosen Rachel , Cocjin Jose T. , Mousa Hayat 
Published: July 2023

Objectives:
Aerodigestive disorders encompass various pathological conditions affecting the lungs, upper airway, and gastrointestinal tract in children. While advanced care has primarily occurred in specialty centers, many children first present to general pediatric gastroenterologists with aerodigestive symptoms necessitating awareness of these conditions. At the 2021 Annual North American Society for Pediatric Gastroenterology, Hepatology and Nutrition meeting, the aerodigestive Special Interest Group held a full-day symposium entitled, Pediatric Aerodigestive Medicine: Advancing Collaborative Care of Children with Aerodigestive Disorders. The symposium aimed to underline the significance of a multidisciplinary approach to achieve better outcomes for these complex patients.

Methods:
The symposium brought together leading experts to highlight the growing aerodigestive field, promote new scientific and therapeutic strategies, share the structure and benefits of a multidisciplinary approach in diagnosing common and rare aerodigestive disorders, and foster multidisciplinary discussion of complex cases while highlighting the range of therapeutic and diagnostic options. In this article, we showcase the diagnostic and therapeutic approach to oropharyngeal dysphagia (OPD), one of the most common aerodigestive conditions, emphasizing the role of a collaborative model.

Conclusions:
The aerodigestive field has made significant progress and continues to grow due to a unique multidisciplinary, collaborative model of care for these conditions. Despite diagnostic and therapeutic challenges, the multidisciplinary approach has enabled and greatly improved efficient, high-quality, and evidence-based care for patients, including those with OPD.
Place of Death for Young Adults With Chronic Illness
Authors: Gustafson Carolina M. , Higgins Melinda , Wood Kathryn A. , Song Mi-Kyung 
Published: July 2023

Background
Little is known about where young adults with chronic illness die in the United States and factors associated with place of death.

Objectives
This study aimed to examine place of death and factors associated with place of death for young adults with chronic illness using the most recent national data.

Methods
Our sample (N = 405,535) from the National Center for Health Statistics Division of Vital Statistics death certificate data (2003–2018) included young adults (age 18–39 years) who died from chronic conditions common in childhood or young adulthood. Conditions were grouped by underlying pathophysiology (oncological, cardiovascular, neuromuscular, metabolic, hematological/immunological, renal, chromosomal/congenital, gastrointestinal, and respiratory). Place of death was dichotomized into acute care (inpatient, outpatient/emergency room, and dead on arrival) or nonacute care (home, hospice, nursing home/long-term care, other, and unknown). Examined factors were gender, year of death, age, race (White, Black, Asian/Pacific Islander, American Indian/Alaskan Native), cause of death, and city of residence population (100,000 or greater and under 100,000). Descriptive statistics and logistic regression were used to examine factors related to place of death.

Results
Over half of young adults died in acute care settings. Young adults who were Asian/Pacific Islander or Black or who died from a respiratory or renal cause of death were most likely to die in an acute care setting. Rates of acute care death decreased over the studied years.

Discussion
Many young adults died in an acute care setting. Race and cause of death were the most influential factors associated with place of death. Young adults with an oncological cause of death were less likely to die in an acute care setting than patients with other underlying causes. This may indicate that specific care needs or preferences at the end of life may differ in certain disease populations and may affect place of death. Previous research has shown similar results in other developmental populations; however, given the complex psychosocial concerns that often arise during young adulthood, further research is needed to describe how the young adult status may specifically affect place of death.
The Association of Pediatric Emergency Medicine Physicians' Self-Identified Skills in Suicide Risk Assessment and Management With Training in Mental Health
Authors: Cervantes Paige E. , Tay Ee Tein , Knapp Katrina , Wiener Ethan , Seag Dana E. M. , Richards-Rachlin Shira , Baroni Argelinda , Horwitz Sarah M. 
Published: July 2023

Objective
Because changes to pediatric emergency medicine (PEM) education may help address barriers to youth suicide risk screening programs, this study aimed to understand the impact of formal training in areas that likely include suicide-related practices, developmental-behavioral pediatrics (DBP) and adolescent medicine (AM), on PEM physician-perceived level of training, attitudes, and confidence assessing and managing youth suicide risk.

Methods
Twenty-seven PEM attendings and trainees completed an online survey and were divided into 2 groups: those who had completed DBP and AM rotations (DBP/AM+; n = 20) and those who had not completed either rotation (DBP/AM−; n = 7). We compared perceived level of training, attitudes, and confidence in assessing and managing suicide risk across groups. We also examined the relationship between perceived level of training and confidence. Finally, we conducted exploratory analyses to evaluate the effect of an additional formal rotation in child psychiatry.

Results
The DBP/AM+ and DBP/AM− groups did not differ on perceived level of training or on attitudes and confidence in suicide risk assessment or management. Perceived level of training in assessment and management predicted confidence in both assessing and managing suicide risk. Additional training in child psychiatry was not associated with increased perceived level of training or confidence.

Conclusions
The DBP and AM rotations were not associated with higher perceived levels of suicide risk training or greater confidence; however, perceived level of training predicted physician confidence, suggesting continued efforts to enhance formal PEM education in mental health would be beneficial.
Perceived and Enacted HIV-Related Stigma in Eastern and Southern Sierra Leone: A Psychometric Study of an HIV Stigma Scale
Authors: Yendewa George A. , Kpaka Rashid A. , Sellu Edmond , Yendewa Sahr A. , Massaquoi Samuel P.E. , Cummings Peterlyn E. , Ghazzawi Manal , Barrie Umaru , Dubé Karine , Lakoh Sulaiman , James Peter B. , Salata Robert A. , Babawo Lawrence S. 
Published: July 2023

ABSTRACTBackgroundHIV stigma continues to hinder the care of people with HIV (PWH), especially in low-resource settings. We aimed to adapt and validate a concise HIV stigma scale for perceived HIV stigma in Sierra Leone.MethodsWe enrolled participants in two HIV clinics in Eastern and Southern Sierra Leone in 2022. We assessed perceived stigma using a 12-item adaptation of Berger’s HIV Stigma Scale and enacted stigma using select USAID indicators. We used ordinal logistic regression to identify predictors of perceived stigma and Pearson’s correlation to examine associations between perceived and enacted stigma.Results624 PWH were enrolled. The final adapted 6-item HIV stigma scale demonstrated acceptable internal consistency (Cronbach’s α = 0.72) and a four-factor solution accounting for 84.8% of variance: concern about public attitude (2 items), personalized stigma (2 items), negative self-image (1 item), and disclosure concerns (1 item). The prevalence of perceived HIV stigma was 68.6%, with disclosure concerns as the most prominent contributor. Enacted HIV stigma was reported by only 6.7% of participants, with partner/spousal abandonment and workplace stigma being the most common discriminatory experiences. Employment (β = 0.525, p <0.001), residence in Eastern Sierra Leone (β = 3.215, p < 0.001), and experiencing enacted stigma (β = 0.804, p < 0.001) were significantly associated with perceived stigma. Having a family member or friend with HIV (β = -0.499, p < 0.001), and HIV disclosure (β = -0.710, p < 0.001) were protective against perceived stigma. Enacted stigma strongly correlated with partner abandonment and family isolation (r = 0.223, p < 0.001).ConclusionWe found high levels of perceived HIV stigma, underscoring the need for targeted interventions to combat stigma and promote inclusivity for PWH in Sierra Leone.
Knowledge of Female Genital Cutting among health and social care professionals in Francophone Belgium: A cross-sectional survey
Authors: O’Neill Sarah , Richard Fabienne , Alexander Sophie , Godin Isabelle 
Published: July 2023

AbstractBackgroundThe provision of optimal, equitable and gender-sensitive health care to women and girls with FGM/C is challenging. Research indicates that health professionals in receiving countries lack knowledge, confidence and competence in managing FGM/C. In order to develop policies that are suitable to the wide heterogeneity of women from FGM/C practising groups, it is paramount to identify what appropriate care might consist of and what are the knowledge gaps of health and social-care providers. No previous research has specifically addressed the knowledge and practices of health professionals in Francophone Belgium and the bi-lingual Brussels region.MethodsAn anonymous questionnaire with 24 questions was developed targeting healthcare and social-care professionals. The questionnaire was distributed between 6 May and 30 August 2021via professional organisations for midwifery, social work, GPs, infectious disease specialists, internal medicine, paediatricians and gynaecologists. The results are presented as frequencies, differences in proportions between groups were tested with Pearson’s Chi-square, when applicable. Correlations were tested by the Pearson correlation coefficient. The threshold of statistical significance is 5%.Results460 individuals filled in the questionnaire of which 42% were medical doctors, 6% nurses, 27% midwives and 25% non-medical professionals (social workers and psychologists). 55% of non-medical professionals had provided support for women with FGM/C. Almost 40% of health professionals knew that there were 4 types of FGM and were able to correctly describe them, 15% were unable to correctly describe any of the 4 types. Those who had already provided care for FGM/C were more numerous to know that there were 4 types (52%). Two health professionals had received requests to perform FGM/C. Twenty-seven midwives and medical doctors had received requests for re-infibulation.ConclusionGrowing numbers of health and social care professionals are providing care for women with FGM/C. However, knowledge of FGM/C is suboptimal. Continuous professional training is crucial.
Modeling the impact of Malakit intervention: one more step towards malaria elimination in the Guiana Shield?
Authors: Lambert Yann , Métras Raphaëlle , Sanna Alice , Galindo Muriel , Hiwat Helene , Marchesini Paola , Vreden Stephen , Suárez-Mutis Martha Cecilia , Mesones Lapouble Oscar , Adenis Antoine , Nacher Mathieu , Boëlle Pierre-Yves , Poletto Chiara , Douine Maylis 
Published: July 2023

AbstractBackgroundMalaria elimination in mobile and hard-to-reach populations calls for new, tailored interventions. In the Guiana Shield countries, the malaria burden is high in the population working in illegal gold mining. Between April 2018 and March 2020, we implemented Malakit, a new intervention targeting gold miners, and relying on the distribution of kits for self-diagnosis and self-treatment. In this study, we evaluate the impact of Malakit on malaria transmission.MethodsWe fitted a mathematical model of malaria transmission to surveillance data from Brazil and Suriname, and to prevalence data from cross-sectional surveys, to estimate the change in treatment coverage and reproduction number between the pre-intervention (2014-2018) and intervention (2018-2020) periods.ResultsModel results show that treatment coverage of symptomatic all-species malaria infections increased from 26.4% (95%CrI 22.8, 30.3) prior intervention to 55.1% (95%CrI 49.9, 60.8) during the intervention, leading to a decrease of the reproduction number from 1.19 to 0.86. We estimate that on average 6943 all-species malaria infections were averted during the intervention, corresponding to a 48.7% reduction in incidence and 43.9% reduction in total infection prevalence.DiscussionMalakit had a significant impact on malaria transmission by improving the access to treatment of the population working in illegal gold mining in French Guiana. Building on the regional efforts of the past twenty years, Malakit contributed to another step towards malaria elimination in the Guiana Shield.
Hostile attribution bias shapes neural synchrony in the left ventromedial prefrontal cortex during ambiguous social narratives
Authors: Lyu Yizhou , Su Zishan , Neumann Dawn , Meidenbauer Kimberly L. , Leong Yuan Chang 
Published: July 2023

AbstractHostile attribution bias refers to the tendency to interpret social situations as intentionally hostile. While previous research has focused on its developmental origins and behavioral consequences, the underlying neural mechanisms remain underexplored. Here, we employed functional near infrared spectroscopy (fNIRS) to investigate the neural correlates of hostile attribution bias. While undergoing fNIRS, participants listened to and provided attribution ratings for 21 hypothetical scenarios where a character’s actions resulted in a negative outcome for the listener. Ratings of hostile intentions were averaged to obtain a measure of hostile attribution bias. Using intersubject-representational similarity analysis, we found that participants with similar levels of hostile attribution bias exhibited higher levels of neural synchrony during narrative listening, suggesting shared interpretations of the scenarios. This effect was localized to the left ventromedial prefrontal cortex (VMPFC), and was particularly prominent in scenarios where the character’s intentions were highly ambiguous. We then grouped participants into high and low bias groups based on a median split of their hostile attribution bias scores. A similarity-based classifier trained on the neural data classified participants as having high or low bias with 76% accuracy, indicating that the neural time courses during narrative listening was systematically different between the two groups. Furthermore, hostile attribution bias correlated negatively with attributional complexity, a measure of one’s tendency to consider multifaceted causes when explaining behavior. Our study sheds light on the neural mechanisms underlying hostile attribution bias and highlights the potential of using fNIRS to develop non-intrusive and cost-effective neural markers of this socio-cognitive bias.Significance StatementInferring the intentions from behavior is crucial for adaptive social functioning. A predisposition towards interpreting intentions as hostile is a significant predictor of interpersonal conflict and aggressive tendencies. Using fNIRS, we found that individual differences in hostile attribution bias shaped neural synchrony in the VMPFC while processing real-world social situations. Additionally, we were able to distinguish between participants with high and low hostile attribution bias from neural activity time courses. These results reveal how subjective interpretations of social situations are influenced by hostile attribution bias and reflected in the temporal dynamics of the VMPFC. Our findings lay the groundwork for future studies aimed at understanding the neurobiological basis of socio-cognitive biases, as well as interventions aimed at mitigating these biases.
MARK2 phosphorylates KIF13A at a 14-3-3 binding site to polarize vesicular transport of transferrin receptor within dendrites
Authors: Han Yue , Li Min , Zhao Bingqing , Wang Huichao , Liu Yan , Liu Zhijun , Xu Jiaxi , Yang Rui 
Published: July 2023

AbstractNeurons regulate the microtubule-based transport of certain vesicles selectively into axons or dendrites to ensure proper polarization of function. The mechanism of this polarized vesicle transport is still not fully elucidated, though it is known to involve kinesins, which drive anterograde transport on microtubules. Here we explore how the kinesin-3 family member KIF13A is regulated such that vesicles containing transferrin receptor (TfR) travel only to dendrites. In experiments involving live-cell imaging, knockout of KIF13A, BioID assay, we found that the kinase MARK2 phosphorylates KIF13A at a 14-3-3 binding motif, strengthening interaction of KIF13A with 14-3-3 such that it dissociates from TfR-containing vesicles, which therefore cannot enter axons. Overexpression of KIF13A or knockout of MARK2 leads to axonal transport of TfR-containing vesicles. These results suggest a novel kinesin-based mechanism for polarized transport of vesicles to dendrites.SignificanceOur findings suggest that at least one type of vesicles, those containing transferrin receptor, travel exclusively to dendrites and are excluded from axons because the kinase MARK2 phosphorylates the kinesin KIF13A to promote its separation from vesicles at the proximal axon, preventing vesicle transport into axons, such that they travel only to dendrites. Future studies should explore how this mechanism of polarized vesicle transport supports neuronal function.
Identifying Selectivity Filters in Protein Biosensor for Ligand Screening
Authors: Sahil Mohammad , Singh Jayanti , Sahu Subhankar , Pal Sushant , Yadav Ajit , Anand Ruchi , Mondal Jagannath 
Published: July 2023

AbstractSpecialized sensing mechanisms in bacteria enable the identification of cognate ligands with remarkable selectivity in highly xenobiotic-polluted environments, where these ligands are utilized as energy sources. Here, via an integrated all-atom computer simulation, biochemical assay and isothermal titration calorimetry approaches we determine the molecular basis of MopR, a phenol biosensor’s complex selection process of ligand entry. Our results reveal a set of strategically placed selectivity filters along the ligand entry pathway of MopR. These filters act as checkpoints, screening diverse aromatic ligands at the protein surface based on their chemical features and sizes. Ligands meeting specific criteria are allowed to enter the sensing site in an orientation-dependent manner. Sequence and structural analyses demonstrate the conservation of this ligand entry mechanism across the sensor class, with individual amino acids along the selectivity filter path playing a critical role in ligand selection. Together, this investigation highlights the importance of interactions with the ligand entry pathway, in addition to interactions within the binding pocket, for achieving ligand selectivity in biological sensing. The findings enhance our understanding of ligand selectivity in bacterial phenol biosensors and provide insights for the rational expansion of the biosensor repertoire, particularly for the biotechnologically relevant class of aromatic pollutants.
An interpretable deep learning framework for genome-informed precision oncology
Authors: Ren Shuangxia , Cooper Gregory F , Chen Lujia , Lu Xinghua 
Published: July 2023

AbstractCancers result from aberrations in cellular signaling systems, typically resulting from driver somatic genome alterations (SGAs) in individual tumors. Precision oncology requires understanding the cellular state and selecting medications that induce vulnerability in cancer cells under such conditions. To this end, we developed a computational framework consisting of two components: 1) A representation-learning component, which learns a representation of the cellular signaling systems when perturbed by SGAs, using a biologically-motivated and interpretable deep learning model. 2) A drug-response-prediction component, which predicts the response to drugs by leveraging the information of the cellular state of the cancer cells derived by the first component. Our cell-state-oriented framework significantly enhances the accuracy of genome-informed prediction of drug responses in comparison to models that directly use SGAs as inputs. Importantly, our framework enables the prediction of response to chemotherapy agents based on SGAs, thus expanding genome-informed precision oncology beyond molecularly targeted drugs.