bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of zilucoplan in Japanese patients with generalized myasthenia gravis: A subgroup analysis of the phase III randomized RAISE study
Authors: Utsugisawa Kimiaki , Deguchi Kazushi , Konno Shingo , Masuda Masayuki , Minami Naoya , Murai Hiroyuki , Suzuki Shigeaki , Suzuki Yasushi , Tsujino Akira , Uzawa Akiyuki , Boroojerdi Babak , de la Borderie Guillemette , Brock Melissa , Duda Petra W. , Vanderkelen Mark , Howard James F. 
Published: September 2023

AbstractObjectivesRAISE (NCT04115293) was a randomized, multicenter, double‐blind, placebo‐controlled phase III study of zilucoplan, a macrocyclic peptide and complement component 5 inhibitor with a dual mechanism of action, in patients with acetylcholine receptor autoantibody‐positive generalized myasthenia gravis (MG). RAISE showed clinically meaningful and statistically significant improvements in MG‐specific outcomes in the overall population. Here, we assess efficacy and safety of zilucoplan in patients with generalized myasthenia gravis in the Japanese patients enrolled in RAISE.MethodsAdults with acetylcholine receptor autoantibody‐positive generalized MG (MGFA disease class II–IV) were randomized 1:1 to daily self‐administered subcutaneous zilucoplan 0.3 mg/kg or placebo injections for 12 weeks. The primary efficacy endpoint was change from baseline to week 12 in the MG Activities of Daily Living score. Safety was assessed by the incidence of treatment‐emergent adverse events. Efficacy and safety outcomes of a Japanese subgroup were prespecified.ResultsOverall, 16 Japanese patients were randomized to zilucoplan 0.3 mg/kg (n = 7) or placebo (n = 9). There was a clinically meaningful improvement in the MG Activities of Daily Living score at week 12 for zilucoplan versus placebo in the Japanese population, with least squares mean difference of −4.26 (95% confidence interval −7.40, −1.12), which was comparable with the overall population. The incidence of treatment‐emergent adverse events was similar in both treatment arms, with 57.1% and 55.6% of patients in the zilucoplan and placebo groups, respectively, experiencing treatment‐emergent adverse events.ConclusionsIn a subgroup of Japanese patients, zilucoplan showed clinically meaningful improvement in MG‐specific outcomes with a favorable safety profile, consistent with the overall RAISE population.
Repeated endoscopic ultrasound‐guided fine‐needle biopsy of solid pancreatic lesions after previous nondiagnostic or inconclusive sampling
Authors: Lisotti Andrea , Cominardi Anna , Conti Bellocchi Maria Cristina , Crinò Stefano Francesco , Larghi Alberto , Facciorusso Antonio , Arcidiacono Paolo Giorgio , De Angelis Claudio , Di Matteo Francesco Maria , Fabbri Carlo , Bertani Helga , Togliani Thomas , Rizzatti Gianenrico , Brancaccio Mario , Grillo Antonino , Fantin Alberto , Pezzoli Alessandro , D'Errico Francesca , Amato Arnaldo , Antonini Filippo , Montale Amedeo , Pisani Antonio , Forti Edoardo , Manno Mauro , Carrara Silvia , Petrone Maria Chiara , Binda Cecilia , Zagari Rocco Maurizio , Fusaroli Pietro ,   the REUBIO Study Group
Published: September 2023

ObjectivesRepeated endoscopic ultrasound (EUS)‐guided tissue acquisition represents the standard practice for solid pancreatic lesions after previous nondiagnostic or inconclusive results. Since data are lacking, we aimed to evaluate the diagnostic performance of repeated EUS fine‐needle biopsy (rEUS‐FNB) in this setting. The primary outcome was diagnostic accuracy; sample adequacy, sensitivity, specificity, and safety were secondary outcomes.MethodsConsecutive patients undergoing rEUS‐FNB for solid pancreatic lesions at 23 Italian centers from 2019 to 2021 were retrieved. Pathology on the surgical specimen, malignant histology together with ≥6‐month follow‐up, and benign pathology together with ≥12‐month follow‐up were adopted as gold standards.ResultsAmong 462 patients, 56.5% were male, with a median age of 68 (59–75) years, malignancy prevalence 77.0%. Tumor size was 26 (20–35) mm. Second‐generation FNB needles were used in 89.6% cases. Diagnostic accuracy, sensitivity, and specificity of rEUS‐FNB were 89.2%, 91.4%, and 81.7%, respectively (19 false‐negative and 12 false‐positive results). On multivariate analysis, rEUS‐FNB performed at high‐volume centers (odds ratio [OR] 2.12; 95% confidence interval [CI] 1.10–3.17; P = 0.03) and tumor size (OR 1.03; 95% CI 1.00–1.06; P = 0.05) were independently related to diagnostic accuracy. Sample adequacy was 94.2%. Use of second‐generation FNB needles (OR 5.42; 95% CI 2.30–12.77; P < 0.001) and tumor size >23 mm (OR 3.04; 95% CI 1.31–7.06; P = 0.009) were independently related to sample adequacy.ConclusionRepeated EUS‐FNB allowed optimal diagnostic performance after nondiagnostic or inconclusive results. Patients' referral to high‐volume centers improved diagnostic accuracy. The use of second‐generation FNB needles significantly improved sample adequacy over standard EUS‐FNB needles.
Changes in serotonin neurotransmission as assayed by microdialysis after acute, intermittent or chronic ethanol administration and withdrawal
Authors: Dahchour Abdelkader , Ward Roberta J. 
Published: September 2023

AbstractBackgroundThe serotonergic neurotransmitter system is involved in many ethanol‐induced changes, including many behavioural alterations, as well as contributing to alcohol dependence and its withdrawal.AimsThis review has evaluated microdialysis studies where alterations in the serotonin system, that is, serotonin, 5‐HT, or its metabolite 5‐hydroxyindoleacetic acid, 5‐HIAA, have been reported during different ethanol intoxication states, as well as in animals showing alcohol preference or not. Changes in 5‐HT receptors and the 5‐HT transporter are briefly reviewed to comprehend the significance of changes in microdialysate 5‐HT concentrations.Materials and methodsChanges in 5‐HT content following acute, chronic and during ethanol withdrawal states are evaluated. In addition, the serotoninergic system was assessed in animals that have been genetically selected for alcohol preference to ascertain whether changes in this monoamine microdialysate content may contribute to alcohol preference.Results and discussionChanges occurred in 5‐HT signalling in the limbic brain regions, increasing after acute ethanol administration in specific brain regions, particularly at higher doses, while chronic alcohol exposure essentially decreased serotonergic transmission. Such changes may play a pivotal role in emotion‐driven craving and relapse. Depending on the dosage, mode of administration and consumption rate, ethanol affects specific brain regions in different ways, enhancing or reducing 5‐HT microdialysate content, thereby inducing behavioural and cognitive functions and enhancing ethanol consumption.ConclusionMicrodialysis studies demonstrated that ethanol induces several alterations in 5‐HT content as well as its metabolites, 5‐HIAA and 5‐HTOL, not only in its release from a specific brain region but also in the modifications of its different receptor subtypes and its transporter.
Morphological differences between wild and hatchery‐reared Bloater (Coregonus hoyi) from Lake Michigan, USA
Authors: Honsey Andrew E. , Kao Yu‐Chun , Olds Chris , Bunnell David B. 
Published: September 2023

AbstractCoregonines (ciscoes and whitefishes) are economically, ecologically, and culturally important fishes that are distributed throughout the Northern Hemisphere. In the Laurentian Great Lakes, coregonines declined throughout the 19th and 20th centuries, and managers have prioritized their restoration. A key restoration tool is reintroduction via stocking. However, hatchery‐reared coregonines can display different morphologies than wild fish, which could affect their fitness. Unfortunately, our understanding of these differences is limited because previous work did not adequately remove allometric effects in morphological analyses. We compared morphologies between wild and hatchery‐reared Bloater (Coregonus hoyi) from the same stock using appropriate size corrections. Hatchery‐reared fish had shorter heads, shorter dorsal fins, and shallower bodies than wild fish. Moreover, some characters differed across wild fish collections. Our results improve our understanding of how artificial rearing can impact coregonine morphology, and we recommend future studies on what causes these differences and whether they impact fitness.
Pharmacological elevation of sphingosine‐1‐phosphate by S1P lyase inhibition accelerates bone regeneration after post‐traumatic osteomyelitis
Authors: Wagner Johannes M. , Wille Annalena , Fueth Maria , Weske Sarah , Lotzien Sebastian , Reinkemeier Felix , Wallner Christoph , Sogorski Alexander , Dittfeld Stephanie , Becerikli Mustafa , Schildhauer Thomas A. , Lehnhardt Marcus , Levkau Bodo , Behr Björn 
Published: September 2023

AbstractPosttraumatic osteomyelitis and the ensuing bone defects are a debilitating complication after open fractures with little therapeutic options. We have recently identified potent osteoanabolic effects of sphingosine‐1‐phosphate (S1P) signalling and have now tested whether it may beneficially affect bone regeneration after infection. We employed pharmacological S1P lyase inhibition by 4‐deoxypyrodoxin (DOP) to raise S1P levels in vivo in an unicortical long bone defect model of posttraumatic osteomyelitis in mice. In a translational approach, human bone specimens of clinical osteomyelitis patients were treated in organ culture in vitro with DOP. Bone regeneration was assessed by μCT, histomorphometry, immunohistology and gene expression analysis. The role of S1P receptors was addressed using S1PR3 deficient mice. Here, we present data that DOP treatment markedly enhanced osteogenesis in posttraumatic osteomyelitis. This was accompanied by greatly improved osteoblastogenesis and enhanced angiogenesis in the callus accompanied by osteoclast‐mediated bone remodelling. We also identified the target of increased S1P to be the S1PR3 as S1PR3−/− mice showed no improvement of bone regeneration by DOP. In the human bone explants, bone mass significantly increased along with enhanced osteoblastogenesis and angiogenesis. Our data suggest that enhancement of S1P/S1PR3 signalling may be a promising therapeutic target for bone regeneration in posttraumatic osteomyelitis.
Sexual and gender minority health‐related content in geriatric fellowships
Authors: Burton Carl Henry , van Zuilen Maria H. , Primbas Angela , Young Megan E. , Swartz Kristine , Colburn Jessica , Kumar Chandrika , Klomhaus Alexandra , Chippendale Ryan , Streed Carl G. 
Published: September 2023

AbstractIntroductionDespite a growing number of older lesbian, gay, bisexual transgender, and queer (LGBTQ) adults in the United States, education on care for this vulnerable population has historically been inadequate across all levels of training. This research assessed the extent of LGBTQ education in geriatric medicine fellowship curricula across the United States.MethodsWe designed a survey to anonymously collect information from geriatric medicine fellowship programs on LGBTQ curricular content. Eligible participants included all 160 fellowship directors on record with the American Geriatrics Society. The survey addressed demographics of the fellowship program, current state of inclusion of LGBTQ content in didactic curricula and in clinical settings, and other available training opportunities.ResultsOut of those contacted, 80 (50%) completed the survey. Of the programs surveyed, 60 (75%) were housed in internal medicine, 19 (24%) were in family medicine, and one was in their own department. Forty‐seven fellowships (59%) reported some formal didactic session (e.g., lecture or case based), with the majority of these programs (72%) featuring 1–2 h of formal instruction. Forty‐five programs (56%) reported offering no formal clinical experiences. There was less than 50% coverage for all surveyed topics in the required curriculum (range 46% for discrimination to 9% for gender affirming care). Time and lack of expertise were cited as the main barriers to content inclusion.ConclusionsCurricular content regarding care for LGBTQ older adults is inadequate in geriatric medicine fellowships. Faculty development of current educators and providing standardized guidelines and curricula are steps toward addressing this deficit.
Comparison of fine‐needle aspiration techniques
Authors: Dufour Jason P. , Allers Carolina , Schiro Faith , Falkenstein Kathrine P. , Gregoire Kayleigh K. , Glover Colin D. , Chamel Alayna N. , Woods Adrienne , Phillippi Jonah P. , Gideon Taylor M. , Kaur Amitinder 
Published: September 2023

AbstractBackgroundFine‐needle aspiration (FNA) has been reported since 1912 beginning with the use of trocars and other specialized instruments that were impractical. Since then, FNA has proven to be a successful alternative technique to excisional biopsy for some assays despite a few limitations.MethodsIn this study, we compared four different techniques for FNA in rhesus macaques by evaluating total live cells recovered and cell viability using a standard 6 mL syringe and 1.5‐inch 22‐gauge needle.ResultsTechnique B which was the only technique in which the needle was removed from the syringe after collection of the sample to allow forced air through the needle to expel the contents into media followed by flushing of the syringe and needle resulted in the highest total cell count and second highest cell viability in recovered cells.ConclusionBased on our results, Technique B appears to be the superior method.
White matter abnormalities mediate the association between masticatory dysfunction and cognition among older adults
Authors: Hedberg Linn , Kumar Abhishek , Skott Pia , Smedberg Jan‐Ivan , Seiger Åke , Sandborgh‐Englund Gunilla , Nordin Love Engström , Kåreholt Ingemar , Tzortzakakis Antonios , Westman Eric , Trulsson Mats , Ekman Urban 
Published: September 2023

AbstractBackgroundMasticatory parameters, such as reduced number of teeth and posterior contacts, have been shown to be associated with reduced cognitive status. The underlying mechanisms that affect these associations, are however, not well understood.ObjectivesThe study aims to investigate the association between masticatory dysfunction and cognition and explore the mediating effect of brain structure.MethodsIn this cross‐sectional study, 45 older adults with subjective masticatory dysfunction (mean age 72.3 ± 4.0 years) were included. Mini‐Mental State Examination score <25, brain trauma, neurological disease, neurodegenerative disorders, depression or poor Swedish language skills were criteria for exclusion. Cognitive functions (executive function and episodic memory) and masticatory dysfunction defined by functional occluding status (FOS; the number of occluding units and number of remaining teeth) were analysed with partial correlation models. Structural magnetic resonance imaging was performed on 28 feasible participants. Multiple regression analyses were performed to evaluate the predictive value of brain structure and white matter hypointensities (WM‐hypo) on cognitive functions. A mediation analysis was applied to assess significant predictor/s of the association between FOS and cognition.ResultsBoth episodic memory and executive functions were positively correlated with FOS. WM‐hypo predicted cognitive status (executive function, p ≤ .01). WM‐hypo mediated 66.6% (p = 0.06) of the association between FOS and executive functions.ConclusionAssociations between FOS and cognitive functions are reported, where FOS, a potential modifiable risk factor, was related to both episodic memory and executive functions. The mediating effect of WM‐hypo on the association between FOS and executive functions highlights the impact of the vascularisation of the brain on the link between mastication and cognition. The present study provides increased knowledge that bridges the gap between masticatory dysfunction and cognition.
Maternal involvement and adolescents' psychological and academic adjustment after COVID‐19 return‐to‐school: A one‐year longitudinal study
Authors: Zhou Tong , Kong Xiaoxue , Bian Xiaohua , Wang Shuotian , Liu Junsheng , Schmidt Louis A. 
Published: September 2023

AbstractThe current study examined the idea that maternal involvement during the COVID‐19 school closure period could contribute to the development of adolescents' daily routines, which could ultimately associate with their psychological and academic adjustment after return‐to‐school. Data were collected from 520 Chinese adolescents (Mage = 12.75 years, SDage = 1.48 years) and their mothers during the COVID‐19 school closure and one year after return‐to‐school. Results indicated that maternal involvement in both education and leisure activities predicted more consistent adolescents' daily routines during the school closure period and then contributed to their more consistent daily routines after return‐to‐school, resulting in less psychological maladjustment and better academic outcomes. Findings highlight the importance of maternal involvement and daily routines in the context of COVID‐19.
Whole genome sequencing analysis demonstrates therapy‐induced echinocandin resistance in Candida auris isolates
Authors: Spruijtenburg Bram , Ahmad Suhail , Asadzadeh Mohammad , Alfouzan Wadha , Al‐Obaid Inaam , Mokaddas Eiman , Meijer Eelco F. J. , Meis Jacques F. , de Groot Theun 
Published: September 2023

AbstractCandida auris is an emerging, multidrug‐resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance is rarely found. Previously, immunocompromised patients from Kuwait with C. auris colonisation or infection were treated with echinocandins, and within days to months, resistance was reported in urine isolates. To determine whether the development of echinocandin resistance was due to independent introductions of resistant strains or resulted from intra‐patient resistance development, whole genome sequencing (WGS) single‐nucleotide polymorphism (SNP) analysis was performed on susceptible (n = 26) and echinocandin‐resistant (n = 6) isolates from seven patients. WGS SNP analysis identified three distinct clusters differing 17–127 SNPs from two patients, and the remaining isolates from five patients, respectively. Sequential isolates within patients had a maximum of 11 SNP differences over a time period of 1–10 months. The majority of isolates with reduced susceptibility displayed unique FKS1 substitutions including a novel FKS1M690V substitution, and nearly all were genetically related, ranging from only three to six SNP differences compared to susceptible isolates from the same patient. Resistant isolates from three patients shared the common FKS1S639F substitution; however, WGS analysis did not suggest a common source. These findings strongly indicate that echinocandin resistance is induced during antifungal treatment. Future studies should determine whether such echinocandin‐resistant strains are capable of long‐term colonisation, cause subsequent breakthrough candidiasis, have a propensity to cross‐infect other patients, or remain viable for longer time periods in the hospital environment.
Methods of Immobilization after Achilles Tendon Rupture Repair: A Comparative Study in Rat Model
Authors: Wang Tianliang , Wu Wenjie , Gu Jiaxiang , Hou Ruixing 
Published: September 2023

ObjectiveThe Achilles tendon (AT) is the most frequently ruptured in the human body. Literature describing different immobilization methods' impact on tendon healing after AT repair is lacking. We compare plaster cast, splint, and K‐wire to determine which is the most stable and has the fewest complications.MethodsSixty rats aged 5–6 months were selected to establish Achilles tendon injury in two hind legs model. After suturing the ends of the AT together with a modified “Kessler” method (Prolene 5–0). The skin incision was interrupted and sutured with 1–0 thread. Rats were divided into three immobilization methods (plaster cast group, splint group, and K‐wire group). In plaster cast group, the hind leg was cast with plaster in the extended position of the hip and knee joints, and the ankle joint was at 150°. Splint and K‐wire group used splints and 0.8‐mm K‐wires, separately. The fixed period was 4 weeks. The incidence of stability and complications (death, necrosis of the legs, necrosis of the skin, and incisional infection) were recorded. Differences were detected using the chi‐square test.ResultsWithin 4 weeks observation, K‐wires showed better stability (90%) compared with the other two ways (40% in plaster cast group, 65% in splint group; p < 0.05). Rats immobilized with K‐wires (10%) suffered significantly lower complications compared with plaster cast and splint group (15%; p < 0.05).ConclusionK‐wire has better stability, lower complication rate than other methods. Immobilization with K‐wire may be a promising tool in future clinical Achilles tendon rupture applications.
Application of behavioral economic strategies to enhance recruitment into a pediatric randomized clinical trial for postoperative pain relief: A randomized clinical trial
Authors: Karthic Anitra , Orgil Zandantsetseg , Tram Nguyen K. , Rice‐Weimer Julie , Stevens Jack , Olbrecht Vanessa A. 
Published: September 2023

AbstractIntroductionA major challenge in conducting clinical trials is recruitment. Trial under‐enrollment leads to underpowered studies. Behavioral economics offers strategies that may enhance trial recruitment.This study assessed the impact of behavioral economic strategies versus a standard biological approach to recruit children into a randomized clinical trial assessing a biofeedback‐based virtual reality intervention for postoperative pain management. We hypothesized the behavioral economics‐informed approach would increase enrollment into the future trial, intention to adhere to therapy, acceptability of the intervention, and perceived efficacy while decreasing perception of treatment burden and risk.MethodsThis single‐center, prospective, randomized trial recruited patients 12‐18 years old undergoing surgery requiring postoperative admission and narcotic administration. Patient‐parent dyads were randomized to watch a behavioral economics‐informed (n = 64) or standard biological (n = 66) recruitment video about a study designed to assess impact of a virtual reality pain management intervention.ResultsThere was no difference in rates of intention to enroll in the study between groups (behavioral economics: 75%, control: 79%, p = 0.744) or in median response scores to questions regarding intention to adhere to therapy (4.0 [3.0, 4.0] vs. 4.0 [3.0, 4.0], p=0.084), acceptability of therapy (4.0 [3.0, 4.0] vs. 4.0 [3.0, 4.0], p = 0.376), perceptions of treatment burden (3.0 [3.0, 4.0] vs. 4.0 [3.0, 4.0], p=0.251), and efficacy (3.0 [3.0, 4.0] vs. 3.0 [3.0, 4.0], p = 0.914). Patients in the behavioral economics group were less likely to perceive risk associated with virtual reality versus the control group (behavioral economics: 2.0 [1.0, 2.0], control: 2.0 [2.0, 3.0], p = 0.023).DiscussionA behavioral economics‐informed video did not increase patients’ intentions to enroll into a clinical trial assessing the impact of virtual reality intervention for postoperative pain management.ConclusionEither approach would be sufficient for patient recruitment for this type of clinical trial since the overall intention to enroll rate was 77%.