bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune-related adverse events of anti-PD-1 immune checkpoint inhibitors: a single center experience
Authors: Sebestyén Enikő , Major Nóra , Bodoki Levente , Makai Attila , Balogh Ingrid , Tóth Gábor , Orosz Zsuzsanna , Árkosy Péter , Vaskó Attila , Hodosi Katalin , Szekanecz Zoltán , Szekanecz Éva 
Published: October 2023

ObjectivesImmune checkpoint inhibitors (ICIs) stimulate antitumor immune responses and, in parallel, they might trigger autoimmune and other immunopathological mechanisms eventually leading to immune-related adverse events (irAE). In our study, we assessed patients with malignancies who underwent anti-PD-1 treatment at the University of Debrecen, Clinical Center.Patients and methodsBetween June 2017 and May 2021, 207 patients started ICI treatment at our university. A total of 157 patients received nivolumab and 50 were treated with pembrolizumab. We looked for factors associated with the development of irAEs. In addition to correlation studies, we performed binary logistic regression analysis to determine, which factors were associated with irAEs. We also performed Forward Likelihood Ratio (LR) analysis to determine independent prognostic factors.ResultsAt the time of data analysis, the mean duration of treatment was 2.03 ± 0.69 years. ROC analysis determined that 9 or more treatment cycles were associated with a significantly higher risk of irAEs. A total of 125 patients received ≥9 treatment cycles. Three times more patients were treated with nivolumab than pembrolizumab. Of the 207 patients, 66 (32%) developed irAEs. Among the 66 patients who developed irAEs, 36 patients (55%) developed one, 23 (35%) developed two, while 7 (10%) developed three irAEs in the same patient. The most common irAEs were thyroid (33 cases), dermatological (25 cases), pneumonia (14 cases) and gastrointestinal complications (13 cases). Patients who developed irAEs received significantly more treatment cycles (21.8 ± 18.7 versus 15.8 ± 17.4; p=0.002) and were younger at the start of treatment (60.7 ± 10.8 versus 63.4 ± 10.1 years; p=0.042) compared to patients without irAEs. Pembrolizumab-treated patients developed more but less severe irAEs compared to those receiving nivolumab.ConclusionICI treatment is very effective, however, irAEs may develop. These irAEs might be related to the number of treatment cycles and the type of treated malignancy.
Early biochemical outcomes following neoadjuvant/adjuvant relugolix with stereotactic body radiation therapy for intermediate to high risk prostate cancer
Authors: Gallagher Lindsey , Xiao Jerry , Hsueh Jessica , Shah Sarthak , Danner Malika , Zwart Alan , Ayoob Marilyn , Yung Thomas , Simpson Tiffany , Fallick Mark , Kumar Deepak , Leger Paul , Dawson Nancy A. , Suy Simeng , Collins Sean P. 
Published: October 2023

IntroductionInjectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventionally fractionated radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following relugolix and SBRT for intermediate to high prostate cancer.MethodsRelugolix was initiated at least 2 months prior to SBRT. Interventions to improve adherence were not utilized. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone ≤ 20 ng/dL. Early PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and ≤ 0.2 ng/mL during the first 4 months post SBRT.ResultsBetween July 2021 and January 2023, 52 men were treated at Georgetown with relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were African American and 28.8% were obese (BMI ≥30 kg/m2). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were ≥ Grade Group 3. 44 patients were intermediate- and 8 were high-risk. Patients initiated relugolix at a median of 3.6 months prior to SBRT with a median duration of 6.2 total months. 92.3% of patients achieved profound castration during relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively.DiscussionRelugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. We observed a 96% testosterone suppresion rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients with localized prostate cancer can consistently and successfully follow an oral ADT protocol without daily reminders. Given relugolix’s potential benefits over injectable GnRH receptor agonists, its usage may be preferred in specific patient populations (fear of needles, prior cardiovascular events). Future studies should focus on boundaries to adherence in specific underserved populations.
Cytokine responses to SARS-COV2 infection in mother-infant dyads: a systematic review and meta-analysis
Authors: Jain Samhita , Allen Isabel Elaine , Song Dongli , Piao Xianhua 
Published: October 2023

BackgroundThe COVID-19 pandemic has affected a significant number of pregnant women worldwide, but studies on immune responses have presented conflicting results. This study aims to systematically review cytokine profiles in pregnant women with SARS-CoV-2 infection and their infants to evaluate immune responses and potential transplacental transfer of cytokines.Materials and methodsA comprehensive search of 4 databases was conducted to identify relevant studies. Inclusion criteria included studies measuring individual cytokines in pregnant women and/or their neonates. Studies were evaluated for quality, and data were extracted for analysis. Meta-analyses were performed using the random-effects model.ResultsSeventeen studies met the inclusion criteria, including data from 748 pregnant women and 287 infants. More than three of these studies evaluated data of 20 cytokines in maternal serum, and data of 10 cytokines was available from cord blood samples. Only the serum level of CXCL10 was significantly up-regulated in SARS-CoV-2 positive pregnant women (n = 339) compared to SARS-CoV-2 negative pregnant women (n = 409). Subset analysis of maternal samples (n = 183) collected during the acute phase of COVID-19 infection showed elevated CXCL10 and IFN-γ. No significant differences in cytokine levels were found between cord blood samples collected from infants born to mothers with (n = 97) and without (n = 190) COVID-19 during gestation. Subset analysis of cord blood samples collected during the acute phase of maternal infection was limited by insufficient data. The heterogeneity among the studies was substantial.ConclusionThe findings suggest that maternal cytokines responses to SARS-CoV-2 infection during pregnancy are not significantly dysregulated, except for CXCL10 and IFN-γ during the acute phase of illness. No evidence of increased cytokine levels in cord blood samples was observed, although this could be impacted by the time period between initial maternal infection and cord blood collection. These results provide some reassurance to parents and healthcare providers but should be interpreted cautiously due to study variations and limitations.
NFIA haploinsufficiency: case series and literature review
Authors: Dini Gianluca , Verrotti Alberto , Gorello Paolo , Soliani Luca , Cordelli Duccio Maria , Antona Vincenzo , Mencarelli Amedea , Colavito Davide , Prontera Paolo 
Published: October 2023

BackgroundNFIA-related disorder (OMIM #613735) is an autosomal dominant neurodevelopmental disorder characterized by a variable degree of cognitive impairment and non-specific dysmorphic features. To date, fewer than thirty patients affected by this disorder have been described.MethodsOur study included three children with NFIA haploinsufficiency recruited from three medical genetics centers. Clinical presentations were recorded on a standardized case report form.ResultsAll patients presented a variable degree of intellectual disability. None of the individuals in our cohort had urinary tract malformations. Three novel mutations, c.344G&gt;A, c.261T&gt;G, and c.887_888del are reported here.ConclusionNFIA haploinsufficiency can be suspected through careful observation of specific dysmorphisms, including macrocephaly and craniofacial abnormalities. Instrumental tests such as MRI and renal ultrasound provide further diagnostic clues, while genetic testing can confirm the diagnosis.
Herbal medicine for the treatment of chronic cough: a systematic review and meta-analysis
Authors: Lee Boram , Kwon Chan-Young , Suh Hyo-Weon , Kim Ye Ji , Kim Kwan-Il , Lee Beom-Joon , Lee Jun-Hwan 
Published: October 2023

Objectives: Chronic cough is a frequent condition worldwide that significantly impairs quality of life. Herbal medicine (HM) has been used to treat chronic cough due to the limited effectiveness of conventional medications. This study aimed to summarize and determine the effects of HM on patients with chronic cough.Methods: A comprehensive search of 11 databases was conducted to find randomized controlled clinical trials (RCTs) that reported the effects of HM for patients with chronic cough on 16 March 2023. The primary outcome was cough severity, and the secondary outcomes included cough-related quality of life, cough frequency, total effective rate (TER), and cough recurrence rate. The methodological quality of the included studies was assessed using the Cochrane risk of bias tool, and the certainty of the evidence for effect estimates was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations tool.Results: A total of 80 RCTs comprising 7,573 patients were included. When HM was used as an alternative therapy to conventional medication, there were inconsistent results in improving cough severity. However, HM significantly improved cough-related quality of life and TER and significantly lowered the cough recurrence rate compared with conventional medication. When used as an add-on therapy to conventional medication, HM significantly improved cough severity, cough-related quality of life, and TER and significantly lowered the recurrence rate. In addition, HM had a significantly lower incidence of adverse events when used as an add-on or alternative therapy to conventional medication. The subgroup analysis according to age and cause of cough also showed a statistically consistent correlation with the overall results. The certainty of the evidence for the effect of HM was generally moderate to low due to the risk of bias in the included studies.Conclusion: HM may improve cough severity and cough-related quality of life, and lower the cough recurrence rate and incidence of adverse events in patients with chronic cough. However, due to the high risk of bias and clinical heterogeneity of the included studies, further high-quality placebo-controlled clinical trials should be conducted using a validated and objective assessment tool.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023418736, CRD42023418736.
Effectiveness of an educational intervention about inhalation technique in healthcare professionals in primary care: a cluster randomized trial
Authors: Vázquez-González Noemí , Leiva-Fernández José , Cotta-Luque Víctor M. , Leiva-Fernández Francisca , Rius-Díaz Francisca , Martos-Crespo Francisco , Martín-Montañez Elisa , Barnestein-Fonseca Pilar 
Published: October 2023

Background: Incorrect inhalation technique (IT) is an important issue for chronic obstructive pulmonary disease (COPD) patients and healthcare professionals. Studies in which counseling is carried out with healthcare professionals beforehand so that they can properly educate their patients are required. The objective of the present trial is to assess the improvement in the performance of the IT in subjects with COPD and prescribed inhaled therapy after the implementation of an educational intervention conducted by their general practitioners.Methods: A cluster randomized clinical trial was conducted. A total of 286 COPD patients received scheduled inhalation therapy from 27 general practices in seven primary care centers. A teach-back educational intervention was implemented for both healthcare professionals and patients. The primary outcome of this study was the performance of the correct inhalation technique. It is considered a good technique if all steps in the inhalation data sheet are correctly performed. The secondary outcomes were assessed using forced spirometry, the basal dyspnea index, the Medical Research Council dyspnea scale, St George’s Respiratory Questionnaire (SGRQ), and EuroQoL5D-5L for health-related quality of life. A one-year follow-up was conducted using an intention-to-treat analysis.Results: After the intervention, incorrect IT was observed in 92% of professionals and patients, with rates reaching 50% and 69.2%, respectively. The effectiveness in patients was significant, with a number needed to treat of 2.14 (95% CI 1.79–2.66). Factors related to correct IT in patients included the type of intervention, length of intervention (&gt;25 min), good pulmonary function, age (youngest &lt;=65, oldest &gt;83), and less limitation of activity due to dyspnea. There was no relation with the cluster.Conclusion: This study shows the effectiveness of direct inhaler technique training provided by a trained professional on an appropriate timescale (for example, a specific consultation for medication reviews), aiming to help subjects improve their performance using the teach-back method. This could be an encouraging intervention to improve medication adherence and health promotion in people with COPD.Clinical Trial Registration:clinicaltrials.gov, identifier ISRCTN93725230.
Pharmacokinetics and tissue distribution of four major bioactive components of Cynanchum auriculatum extract: a UPLC–MS/MS study in normal and functional dyspepsia rats
Authors: Sun Jia , Meng Xin , Huang Di , Gong Zipeng , Liu Chunhua , Liu Ting , Pan Jie , Lu Yuan , Zheng Lin 
Published: October 2023

Introduction:Cynanchum auriculatum (CA) is usually used to treat digestive disorders, such as anorexia, enteritis, dysentery, and indigestion. Functional dyspepsia (FD) is characterized by a group of symptoms associated with the gastroduodenal region. Recent pharmacological studies have demonstrated the efficacy of CA for treating FD. However, the pharmacokinetics (PK) and tissue distribution of CA in physiological and FD states is still unclear. The present study aimed to clarify the differences in PK parameters and tissue distribution of the four major active components of CA (baishouwu benzophenone, deacylmet-aplexigenin, qingyangshengenin, and syringic acid) under both physiological and FD states.Methods: For this, normal and FD rats were orally administered 10 mg/kg CA extract. Then, plasma and tissue (heart, liver, spleen, lung, kidney, brain, stomach, and small intestine) samples were obtained. The four active components of CA in rat plasma and tissues were quantified by developing and validating a fast and reliable ultra–high–performance liquid chromatography–mass spectrometry method.Results: The area under the plasma concentration–time curve from time zero to time t (AUC0-t) of baishouwu benzophenone was significantly lower in the FD group than in the normal group (p &lt; 0.01). The FD group had significantly lower (p &lt; 0.001) apparent volume of distribution and plasma clearance of qing-yangshengenin and significantly higher (p &lt; 0.05) AUC0-t of deacylmetaplexigenin and qingyangshengenin. The four active components were rapidly distributed into various tissues, and the main target organs of CA activity were the stomach and small intestine. In addition, baishouwu benzophenone, deacylmetaplexigenin, and qingyangshengenin could cross the blood-brain barrier, indicating that the brain may be another target organ in the treatment of FD.Discussion: These results indicate that the pathological state of FD alters the PK behavior and tissue distribution characteristics of baishouwu benzophenone, deacylmetaplexigenin, qingyangshengenin, and syringic acid in the CA extract, providing an experimental basis for the role of CA in FD treatment.
Characterization of neurocognitive deficits in patients with post-COVID-19 syndrome: persistence, patients’ complaints, and clinical predictors
Authors: Kozik Valeska , Reuken Philipp , Utech Isabelle , Gramlich Judith , Stallmach Zoe , Demeyere Nele , Rakers Florian , Schwab Matthias , Stallmach Andreas , Finke Kathrin 
Published: October 2023

IntroductionCognitive symptoms persisting beyond 3 months following COVID-19 present a considerable disease burden. We aimed to establish a domain-specific cognitive profile of post-COVID-19 syndrome (PCS). We examined the deficits’ persistence, relationships with subjective cognitive complaints, and clinical variables, to identify the most relevant cognitive deficits and their predictors.MethodsThis cross-sectional study examined cognitive performance and patient-reported and clinical predictors of cognitive deficits in PCS patients (n = 282) and socio-demographically comparable healthy controls (n = 52).ResultsOn the Oxford Cognitive Screen-Plus, the patient group scored significantly lower in delayed verbal memory, attention, and executive functioning than the healthy group. In each affected domain, 10 to 20% of patients performed more than 1.5 SD below the control mean. Delayed memory was particularly affected, with a small effect of hospitalization and age. Attention scores were predicted by hospitalization and fatigue.DiscussionThus, PCS is associated with long-term cognitive dysfunction, particularly in delayed memory, attention, and executive functioning. Memory deficits seem to be of particular relevance to patients’ experience of subjective impairment. Hospitalization, fatigue, and age seem to predict cognitive deficits, while time since infection, depression, and pre-existing conditions do not.
An 18-week model of Parent–Child Interaction Therapy: clinical approaches, treatment formats, and predictors of success for predominantly minoritized families
Authors: Jent Jason F. , Rothenberg William A. , Peskin Abigail , Acosta Juliana , Weinstein Allison , Concepcion Raquel , Dale Chelsea , Bonatakis Jessica , Sobalvarro Cindy , Chavez Felipa , Hernandez Noelia , Davis Eileen , Garcia Dainelys 
Published: October 2023

IntroductionDisruptive behavior disorders are among the most prevalent pediatric mental health referrals for young children. However, families from historically minoritized social identities have experienced disparities in treatment access, retention, and outcomes. Evidence-based interventions such as Parent–Child Interaction Therapy (PCIT) have been found to be effective in reducing children’s disruptive behaviors in minoritized families. However, variable treatment length as a result of skill-based graduation criteria (e.g., observed caregiver verbalizations) may slow and/or hinder treatment progress, particularly for families where expected treatment verbalizations are less linguistically relative (e.g., no exact English to Spanish translations) and/or culturally familiar. Time-limited PCIT has been proposed as a strategy for promoting equity in treatment completion and outcomes amongst minoritized families, because treatment progression and/ or completion is not contingent upon caregiver linguistic skill demonstration.MethodsThe current study evaluated the overall effectiveness of an 18-week model of PCIT and examined predictors of retention and treatment outcomes. Participants (N = 488 dyads) included predominantly racially, ethnically, linguistically, and socioeconomically diverse children aged two to eight years, and their caregivers.ResultsOverall findings indicate that the 18-week PCIT model is an effective intervention for reducing children’s externalizing and internalizing behaviors and improving caregiver parenting skills for most treatment completers. Despite advances in treatment completion, some caregiver social identities and PCIT treatment characteristics were predictive of lower completion rates and/or less optimal treatment outcomes.DiscussionOverall, this study provides strong support for widely disseminating use of the 18-week model of PCIT for most families served. Clinical implications and considerations for continued treatment inequity are discussed.
Research on the impact of basic psychological needs satisfaction on career adaptability of Chinese college students
Authors: Xu Min , Lu Haidong , Guo Qi 
Published: October 2023

IntroductionWith social changes, the realization of smooth and satisfactory employment of college students is an issue that requires deep thought. Basic psychological needs satisfaction play an important role as a guiding factor that affects students’ career adaptability. This study aims to explore the relationship and mechanism between the satisfaction of students’ basic psychological needs satisfaction and their career adaptability.MethodsA survey is conducted among students from six different universities across the country, using the Basic Psychological Needs Satisfaction Scale, the Career Adaptability Scale, the Career Decision Self-Efficacy Scale, and the Career Outcome Expectations Scale.ResultsThe satisfaction of basic psychological needs, career decision self-efficacy, and career outcome expectations are all significantly positively correlated with career adaptability.Career decision self-efficacy plays a partial mediating role between basic psychological needs satisfaction and career adaptability among college students. The moderated mediation model found that career outcome expectations play a regulatory role in the effect of career decision self-efficacy on career adaptability.DiscussionCollege students’ basic psychological need satisfaction can positively predict career adaptability directly and indirectly affect career adaptability through career decision self-efficacy, and career outcome expectations have a moderating role between career decision self-efficacy and career adaptability.