bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal predictive probability designs for randomized biomarker-guided oncology trials
Authors: Zabor Emily C. , Kaizer Alexander M. , Pennell Nathan A. , Hobbs Brian P. 
Published: December 2022

IntroductionEfforts to develop biomarker-targeted anti-cancer therapies have progressed rapidly in recent years. With efforts to expedite regulatory reviews of promising therapies, several targeted cancer therapies have been granted accelerated approval on the basis of evidence acquired in single-arm phase II clinical trials. And yet, in the absence of randomization, patient prognosis for progression-free survival and overall survival may not have been studied under standard of care chemotherapies for emerging biomarker subpopulations prior to the submission of an accelerated approval application. Historical control rates used to design and evaluate emerging targeted therapies often arise as population averages, lacking specificity to the targeted genetic or immunophenotypic profile. Thus, historical trial results are inherently limited for inferring the potential “comparative efficacy” of novel targeted therapies. Consequently, randomization may be unavoidable in this setting. Innovations in design methodology are needed, however, to enable efficient implementation of randomized trials for agents that target biomarker subpopulations.MethodsThis article proposes three randomized designs for early phase biomarker-guided oncology clinical trials. Each design utilizes the optimal efficiency predictive probability method to monitor multiple biomarker subpopulations for futility. Only designs with type I error between 0.05 and 0.1 and power of at least 0.8 were considered when selecting an optimal efficiency design from among the candidate designs formed by different combinations of posterior and predictive threshold. A simulation study motivated by the results reported in a recent clinical trial studying atezolizumab treatment in patients with locally advanced or metastatic urothelial carcinoma is used to evaluate the operating characteristics of the various designs.ResultsOut of a maximum of 300 total patients, we find that the enrichment design has an average total sample size under the null of 101.0 and a total average sample size under the alternative of 218.0, as compared to 144.8 and 213.8 under the null and alternative, respectively, for the stratified control arm design. The pooled control arm design enrolled a total of 113.2 patients under the null and 159.6 under the alternative, out of a maximum of 200. These average sample sizes that are 23-48% smaller under the alternative and 47-64% smaller under the null, as compared to the realized sample size of 310 patients in the phase II study of atezolizumab.DiscussionOur findings suggest that potentially smaller phase II trials to those used in practice can be designed using randomization and futility stopping to efficiently obtain more information about both the treatment and control groups prior to phase III study.
The efficacy and safety of epidural morphine/hydromorphone in the treatment of intractable postherpetic neuralgia: A single-center, double-blinded, randomized controlled, prospective, and non-inferiority study
Authors: Yiping Sun , Jiayi Shen , Guang Hei , Yun Ji , Bingjie Ma , Xuehua Huang , Zhiyuan Yu , Pingchuan Ma , Ke Ma 
Published: December 2022

Objective: Postherpetic neuralgia (PHN) is a clinical puzzle, especially in patients who still suffered from moderate and severe pain after standard treatment. This single-center, double-blinded, randomized controlled, prospective, and non-inferiority study observed the safety and effectiveness of the epidural application of morphine or hydromorphone, trying to provide an alternative method for those patients with refractory PHN.Methods: Eighty PHN patients with a visual analogue scale (VAS) still greater than 50 mm after routine management were randomly divided into two groups according to 1:1, respectively. One group received epidural morphine (EMO group), and the other group received epidural hydromorphone (EHM group). VAS, the number of breakthrough pain, quality of life (QOL), and anxiety/depression assessment (GAD-7 and PHQ-9 scores) were also observed before treatment, at 1, 3, 7, 14, 21, 28, 60, and 90 days after treatment, as well as side effects. Opioid withdrawal symptoms (OWSs) were also measured from 3 to 28 days after treatment.Results: The EHM group was non-inferior to the EMO group in terms of the VAS decrease relative to baseline (VDRB) after 1-week treatment. The VAS of the two groups on all days after treatment was significantly lower than the corresponding baseline findings (p &lt; 0.05). The breakthrough pain (BTP) decreased significantly after treatment and lasted until 14 days after treatment (p &lt; 0.05). There was no significant difference in BTP between the two groups at each time point (p &gt; 0.05). In terms of the QOL, GAD-7, and PHQ-9 outcomes, those were significantly improved after treatment (p &lt; 0.05), and there was no difference between the two groups (p &gt; 0.05). No significant AE difference across the two groups was observed in this study. Few reports of OWS were found in this trial, and there were no significant differences between the two groups (p &gt; 0.05).Conclusion: EHM was non-inferior to EMO in terms of the VDRB after 1-week treatment. For patients with VAS still greater than 50 mm after standard treatment, short-term application of EMO or EHM can ameliorate intractable pain, improve the quality of life, and have no obvious side effects. Short-term epidural opioid application will not lead to the appearance of OWS.
The role of tetradecane in the identification of host plants by the mirid bugs Apolygus lucorum and Adelphocoris suturalis and potential application in pest management
Authors: Yin Haichen , Li Wenjing , Xu Min , Xu Dong , Wan Peng 
Published: December 2022

The mirid bugs Apolygus lucorum and Adelphocoris suturalis are considered serious pests of many crops in China, the host plant recognition of these pests remains unclear. The current study investigated the vital odor cues of two mirid bugs and evaluated the role of olfactory recognition in host recognition. The GC-EAD response of mirid bugs to volatiles of their host plant Phaseolus vulgaris was tested. Tetradecane, 2-propyl-1-pentanol, and dodecanal elicited strong EAG responses by mirid bugs and were tested with field experiments. The results indicated tetradecane was significantly more attractive than other attractants, yielding 30.33 ± 2.19 mirid bugs trapped during 7 days. The selected response rates to tetradecane were above 60%, which was most attractive to female A. lucorum at 1.5 mg/ml. Among seven tetradecane derivatives, tetradecane and tetradecanoic acid were the most potent attractants to A. lucorum and A. suturalis. Tetradecane was present in the volatiles of 10 common hosts, and their difference in relative content was significant. The presence of tetradecane seemed relevant to the olfactory response intensity of two mirid bugs towards the different host plants. The artificial supplement of tetradecane increased the attractive effect of host plants. These results suggested that tetradecane plays a vital role in the olfactory selection by two mirid bugs, and it can be made into field baits as a novel ecological strategy to manage these pests with widely reported pesticide resistance. However, results suggested host recognition is not entirely dependent on odor cues. We demonstrated that A. suturalis and A. lucorum adults have similar olfactory recognition mechanisms to their hosts in long-distance host selection. While, the differences in host plant selection between the two pests should occur in close range due to differences in gustatory or tactile sensory organs of A. lucorum and A. suturalis.
Characterization and diagnostic value of the gut microbial composition in patients with minimal change disease
Authors: Zhang Yiding , Zhou Yukun , Cui Wen , Wang Zhihui , Wang Xuemei , Wu Feng , Wang Peipei , Wang Ting , Yu Wei , Wang Li , Shang Jin , Zhao Zhanzheng 
Published: December 2022

Background: Minimal change disease (MCD) is one of the most common causes of primary nephrotic syndrome with high morbidity. This study aimed to explore the typical alterations of gut microbiota in MCD and establish a non-invasive classifier using key gut microbiome. We also aimed to evaluate the therapeutic efficiency of gut microbiota intervention in MCD through animal experiments.Methods: A total of 222 stool samples were collected from MCD patients and healthy controls at the First Affiliated Hospital of Zhengzhou University and Shandong Provincial Hospital for 16S rRNA sequencing. Optimum operational taxonomic units (OTUs) were obtained for constructing a diagnostic model. MCD rat models were established using doxorubicin hydrochloride for exploring the therapeutic efficiency of gut microbial intervention through fecal microbiota transplantation (FMT).Results: The α-diversity of gut microbiota decreased in MCD patients when compared with healthy controls. The relative abundance of bacterial species also changed significantly. We constructed a diagnostic model based on eight optimal OTUs and it achieved efficiency of 97.81% in discovery cohort. The high efficiency of diagnostic model was also validated in the patients with different disease states and cross-regional cohorts. The treatment partially recovered the gut microbial dysbiosis in patients with MCD. In animal experiments, likewise, the gut microbiota changed sharply in MCD rats. However, gut microbial interventions did not reduce urinary protein or pathological kidney damage.Conclusion: Gut Microbiota shifts sharply in both patients and rats with MCD. Typical microbial changes can be used as biomarkers for MCD diagnosis. The gut microbiota compositions in patients with MCD tended to normalize after treatment. However, the intervention of gut microbiota seems to have no therapeutic effect on MCD.
Water use strategies of Ferula bungeana on mega-dunes in the Badain Jaran Desert
Authors: Qin Jie , Si Jianhua , Jia Bing , Zhao Chunyan , Zhou Dongmeng , He Xiaohui , Wang Chunlin , Zhu Xinglin 
Published: December 2022

In desert ecosystems, ephemeral plants have developed specialized water use strategies in response to long-term natural water stress. To examine the water use strategies of desert ephemeral plants under natural extreme drought conditions, we investigated the water absorption sources, water potential, hydraulic conductivity, and water use efficiency of Ferula bungeana at different elevations on the slopes of mega-dunes in the Badain Jaran Desert, Inner Mongolia, during a period of extreme drought. We found that the water utilized by F. bungeana was mostly absorbed from the 0–60 cm soil layers (80.47 ± 4.28%). With progression of the growing season, the source of water changed from the 0–30 cm soil layer to the 30-60 cm layer. The water potentials of the leaves, stems, and roots of F. bungeana were found to be characterized by clear diurnal and monthly variation, which were restricted by water availability and the hydraulic conductivity of different parts of the plant. The root hydraulic conductivity of F. bungeana was found to be considerably greater than that of the canopy, both of which showed significant diurnal and monthly variation. The water use efficiency of F. bungeana under extreme drought conditions was relatively high, particularly during the early and late stages of the growing season. Variations in water availability led to the regulation of water uptake and an adjustment of internal water conduction, which modified plant water use efficiency. These observations tend to indicate that the water use strategies of F. bungeana are mainly associated with the growth stage of plants, whereas the distribution pattern of plants on mega-dunes appeared to have comparatively little influence. Our findings on the water use of ephemeral plants highlight the adaptive mechanisms of these plants in desert habitats and provide a theoretical basis for selecting plants suitable for the restoration and reconstruction of desert ecosystems.
Effect of mindfulness on online impulse buying: Moderated mediation model of problematic internet use and emotional intelligence
Authors: Vihari Nitin Simha , Sinha Nishit Kumar , Tyagi Akansha , Mittal Saurabh 
Published: December 2022

IntroductionOnline impulse buying behavior is an unplanned urge to buy a product or service in an online setting and it has several negative consequences for customers, such as guilt and financial distress, and e-commerce firms, such as higher returns and customer complaints. Evidently, it is important to examine the various psychological processes which may assist in a better understanding, therefore addressing the high prevalence of online impulse buying. This study builds upon self-regulation theory to explore how mindfulness influences online impulse buying, and examines problematic internet use as a mediator in the relationship between mindfulness and online impulse buying. Further, this study investigates how emotional intelligence as a moderator plays the role of a suppressant on the adverse impact of problematic Internet use which fuels online impulse buying.MethodA total of 598 individuals working with various servicebased industries responded to the questionnaire. Multiple regression and moderated mediation analysis was used using SPSS and AMOS for analyzing the data.ResultProblematic internet use mediates the relationship between mindfulness and online impulse buying behavior. Emotional intelligence negatively moderates the relationship between problematic internet use and online impulse buying behavior.DiscussionThis study findings outlined the inverse relationship of mindfulness &amp; online impulse buying, along with the mediating effect of problematic internet use between mindfulness and online impulse buying. Further, this study showed how emotional intelligence played an important role as a moderator by suppressing the adverse impact of problematic Internet use and preventing online impulse buying. The study offers implications to online marketers in regulating the unplanned purchase process—while minimizing uninhibited buying behavior that leads to regret, and the subsequent intention to return products. Further, social and theoretical implications are discussed.
Supporting the inclusion and retention of autistic students: Exploring teachers' and paraeducators' use of evidence-based practices in public elementary schools
Authors: Locke Jill , Hernandez Alyssa M. , Joshi Mahima , Hugh Maria L. , Bravo Alice , Osuna Anthony , Pullmann Michael David 
Published: December 2022

IntroductionEducators in public schools are required to serve students in their least restrictive environment. While many evidence-based practices (EBPs), defined as practices and strategies shown by research to have meaningful effectson outcomes for autistic students are documented in the literature, less is known about EBP use among educators in public schools.MethodsEighty-six general and special education teachers and para educators completed a survey about familiarity, training, and EBP use for included autistic children.ResultsAcross roles, educators reported familiarity (98.8%), use (97.7%), and training (83.7%) in reinforcement. They reported the least familiarity with behavioral momentum (29.1%), training in both video modeling and peer-mediated instruction and intervention (18.6%), and use of video modeling (14.0%). Follow-up interviews (n = 80) highlighted mixed understanding of EBP definitions and use.DiscussionImplications for inclusive education are discussed including autism-specific EBP training within pre-service teacher preparation programs.
Segmental abnormalities of superior longitudinal fasciculus microstructure in patients with schizophrenia, bipolar disorder, and attention-deficit/hyperactivity disorder: An automated fiber quantification tractography study
Authors: Xu Feiyu , Jin Chengliang , Zuo Tiantian , Wang Ruzhan , Yang Ying , Wang Kangcheng 
Published: December 2022

IntroductionSuperior longitudinal fasciculus (SLF) is a white matter (WM) tract that connects the frontal, parietal and temporal lobes. SLF integrity has been widely assessed in neuroimaging studies of psychiatric disorders, such as schizophrenia (SZ), bipolar disorder (BD), and attention-deficit/hyperactivity disorder (ADHD). However, prior studies have revealed inconsistent findings and comparisons across disorders have not been fully examined.MethodsHere, we obtained data for 113 patients (38 patients with SZ, 40 with BD, 35 with ADHD) and 94 healthy controls from the UCLA Consortium for Neuropsychiatric Phenomic LA5c dataset. We assessed the integrity of 20 major WM tracts with a novel segmentation method by automating fiber tract quantification (AFQ). The AFQ divides each tract into 100 equal parts along the direction of travel, with fractional anisotropy (FA) of each part taken as a characteristic. Differences in FA among the four groups were examined.ResultsCompared to healthy controls, patients with SZ showed significantly lower FA in the second half (51–100 parts) of the SLF. No differences were found between BD and healthy controls, nor between ADHD and healthy controls. Results also demonstrated that patients with SZ showed FA reduction in the second half of the SLF relative to patients with BP. Moreover, greater FA in patients in SLF was positively correlated with the manic-hostility score of the Brief Psychiatry Rating scale.DiscussionThese findings indicated that differences in focal changes in SLF might be a key neurobiological abnormality contributing to characterization of these psychiatric disorders.
The effect of malaria on childhood anemia in a quasi-experimental study of 7,384 twins from 23 Sub-Saharan African countries
Authors: Starck Tim , Dambach Peter , Rouamba Toussaint , Tinto Halidou , Osier Faith , Oldenburg Catherine E. , Adam Maya , Bärnighausen Till , Jaenisch Thomas , Bulstra Caroline A. 
Published: December 2022

BackgroundYoung children in Sub-Saharan Africa (SSA), particularly those from resource-limited settings, are heavily burdened by anemia and malaria. While malaria infected children frequently become anemic (hemoglobin &lt; 110 g/L), anemia is a strongly multifactorial disease with many other risk factors than malaria. Due to the complex and often overlapping contributors to anemia, it remains challenging to isolate the true impact of malaria on population level hemoglobin concentrations.MethodsWe quantified the malaria-induced effect on hemoglobin levels in children under 5 years of age, leveraging data from 7,384 twins and other multiples, aged 6 to 59 months, from 57 nationally representative Demographic and Health Surveys (DHSs) from 23 SSA countries from 2006 to 2019. The quasi-experimental twin fixed-effect design let us minimize the impact of potential confounders that do not vary between twins.ResultsOur analyses of twins revealed a malaria-induced hemoglobin decrease in infected twins of 9 g/L (95% CI -10; -7, p&lt;0.001). The relative risk of severe anemia was higher (RR = 3.01, 95% CI 1.79; 5.1, p&lt;0.001) among malaria positive children, compared to malaria negative children. Conversely, malaria positive children are only half as likely to be non-anemic (RR = 0.51, 95% CI 0.43; 0.61, p&lt;0.001).ConclusionEven after rigorous control for confounding through a twin fixed-effects study design, malaria substantially decreased hemoglobin levels among SSA twins, rendering them much more susceptible to severe anemia. This effect reflects the population-level effect of malaria on anemia.
Improving Initial Medication Adherence to cardiovascular disease and diabetes treatments in primary care: Pilot trial of a complex intervention
Authors: Corral-Partearroyo Carmen , Sánchez-Viñas Alba , Gil-Girbau Montserrat , Peñarrubia-María María Teresa , Aznar-Lou Ignacio , Serrano-Blanco Antoni , Carbonell-Duacastella Cristina , Gallardo-González Carmen , Olmos-Palenzuela Maria del Carmen , Rubio-Valera Maria 
Published: December 2022

IntroductionThe Initial Medication Adherence (IMA) intervention is a multidisciplinary and shared decision-making intervention to improve initial medication adherence addressed to patients in need of new treatments for cardiovascular diseases and diabetes in primary care (PC). This pilot study aims to evaluate the feasibility and acceptability of the IMA intervention and the feasibility of a cluster-RCT to assess the effectiveness and cost-effectiveness of the intervention.MethodsA 3-month pilot trial with an embedded process evaluation was conducted in five PC centers in Catalonia (Spain). Electronic health data were descriptively analyzed to test the availability and quality of records of the trial outcomes (initiation, implementation, clinical parameters and use of services). Recruitment and retention rates of professionals were analyzed. Twenty-nine semi-structured interviews with professionals (general practitioners, nurses, and community pharmacists) and patients were conducted to assess the feasibility and acceptability of the intervention. Three discussion groups with a total of fifteen patients were performed to review and redesign the intervention decision aids. Qualitative data were thematically analyzed.ResultsA total of 901 new treatments were prescribed to 604 patients. The proportion of missing data in the electronic health records was up to 30% for use of services and around 70% for clinical parameters 5 months before and after a new prescription. Primary and secondary outcomes were within plausible ranges and outliers were barely detected. The IMA intervention and its implementation strategy were considered feasible and acceptable by pilot-study participants. Low recruitment and retention rates, understanding of shared decision-making by professionals, and format and content of decision aids were the main barriers to the feasibility of the IMA intervention.DiscussionInvolving patients in the decision-making process is crucial to achieving better clinical outcomes. The IMA intervention is feasible and showed good acceptability among professionals and patients. However, we identified barriers and facilitators to implementing the intervention and adapting it to a context affected by the COVID-19 pandemic that should be considered before launching a cluster-RCT. This pilot study identified opportunities for refining the intervention and improving the design of the definitive cluster-RCT to evaluate its effectiveness and cost-effectiveness.Clinical trial registrationClinicalTrials.gov, identifier NCT05094986.