bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic accuracy of cerebrospinal fluid biomarkers for the differential diagnosis of sporadic Creutzfeldt–Jakob disease: a (network) meta‐analysis
Authors: Rübsamen Nicole , Pape Stephanie , Konigorski Stefan , Zapf Antonia , Rücker Gerta , Karch André 
Published: January 2022

AbstractBackgroundThere are no systematic reviews of cerebrospinal fluid and blood biomarkers for sporadic Creutzfeldt–Jakob disease (sCJD) in specialized care settings that compare diagnostic accuracies in a network meta‐analysis (NMA).MethodsWe searched Medline, Embase, and Cochrane Library for diagnostic studies of sCJD biomarkers. Studies had to use established diagnostic criteria for sCJD and for diseases in the non‐CJD groups, which had to represent a consecutive population of patients suspected as a CJD case, as reference standard. Risk of bias was assessed with QUADAS‐2. We conducted individual biomarker meta‐analyses with generalized bivariate models. To investigate heterogeneity, we performed subgroup analyses based on QUADAS‐2 quality and clinical criteria. For the NMA, we applied a Bayesian beta‐binomial ANOVA model. The study protocol was registered at PROSPERO (CRD42019118830).ResultsOf 2976 publications screened, we included 16 studies, which investigated 14–3‐3β (n = 13), 14–3‐3γ (n = 3), neurofilament light chain (NfL, n = 1), neuron‐specific enolase (n = 1), p‐tau181/t‐tau ratio (n = 2), RT‐QuIC (n = 7), S100B (n = 3), t‐tau (n = 12), and t‐tau/Aβ42 ratio (n = 1). Excluded diagnostic studies had strong limitations in study design. In the NMA, RT‐QuIC (0.91; 95% CI [0.83, 0.95]) and NfL (0.93 [0.78, 0.99]) were the most sensitive biomarkers for the diagnosis of definite, probable, and possible sCJD cases. RT‐QuIC was the most specific biomarker (0.97 [0.89, 1.00]). Heterogeneity in accuracy estimates was high between studies.ConclusionsWe identified RT‐QuIC as the most accurate biomarker, partially confirming currently applied diagnostic criteria. The shortcomings identified in many diagnostic studies for sCJD biomarkers need to be addressed in future studies.
Epithelial miR‐215 negatively modulates Th17‐dominant inflammation by inhibiting CXCL12 production in the small intestine
Authors: Pareek Siddhika , Sanchenkova Xenia , Sakaguchi Taiki , Murakami Mari , Okumura Ryu , Kayama Hisako , Kawauchi Saya , Motooka Daisuke , Nakamura Shota , Okuzaki Daisuke , Kishimoto Tadamitsu , Takeda Kiyoshi 
Published: January 2022

AbstractMicroRNAs are a class of non‐coding short‐chained RNAs that control cellular functions by downregulating their target genes. Recent research indicates that microRNAs play a role in the maintenance of gut homeostasis. miR‐215 was found to be highly expressed in epithelial cells of the small intestine; however, the involvement of miR‐215 in gut immunity remains unknown. Here, we show that miR‐215 negatively regulates inflammation in the small intestine by inhibiting CXCL12 production. Mice lacking miR‐215 showed high susceptibility to inflammation induced by indomethacin, accompanied by an increased number of Th17 cells in the lamina propria of the small intestine. Our findings provide a rationale for targeting miR‐215 as a therapeutic intervention for inflammatory conditions in the small intestine.
Does “wearing off” of efficacy occur in galcanezumab‐treated patients at the end of the monthly treatment cycle? Post hoc analyses of four phase III randomized trials
Authors: Ailani Jessica , Kuruppu Dulanji K. , Rettiganti Mallikarjuna , Oakes Tina , Schroeder Krista , Wietecha Linda , Port Martha , Blumenfeld Andrew M. 
Published: January 2022

AbstractObjectiveThe purpose of this study was to propose a definition of “wearing off” at the individual patient‐level and determine the percentage of patients with migraine who experience “wearing off” of efficacy of galcanezumab at the end of a treatment cycle using this predefined threshold.BackgroundAnecdotal reports suggest that some patients may experience “wearing off” of efficacy during the last week of their calcitonin gene‐related peptide monoclonal antibody treatment cycle. A previous post hoc analysis of galcanezumab demonstrated consistent efficacy at each week throughout all monthly dosing intervals at the population‐level, but “wearing off” has not been assessed at the individual patient‐level.MethodsPost hoc analyses of clinical trial data from four galcanezumab phase III, randomized, placebo‐controlled studies in a total of 2680 patients with high‐frequency episodic migraine (EVOLVE‐1, EVOLVE‐2, and CONQUER studies) or chronic migraine (CM; REGAIN and CONQUER studies) were conducted. “Wearing off” was defined as an increase of greater than or equal to 2 weekly migraine headache days in the last week of the treatment cycle compared to the second week for at least 2 months. The analyses were conducted (1) in all patients and (2) in patients with a clinically meaningful response to treatment.ResultsThe percentage of patients meeting the threshold of “wearing off” was not statistically significantly different among the placebo, galcanezumab 120 mg, and galcanezumab 240 mg treatment groups, both in the total population and in patients with a clinically meaningful response (all ≤9.0%). Although the frequency of “wearing off” in patients with CM and prior preventive failures was numerically greater in the galcanezumab groups (8/89 or 9.0%) compared to placebo (3/95 or 3.2%), these differences were not statistically significant.ConclusionsConsistent with previous analyses at the population‐level that showed no evidence of decreased efficacy at the end of a treatment cycle, rates of individual patients meeting the threshold of “wearing off” in this analysis were low and similar among placebo, galcanezumab 120 mg, and galcanezumab 240 mg treatment groups.
Is nestin a diagnostic marker for combined hepatocellular–cholangiocarcinoma?
Authors: Sasaki M , Sato Y , Nakanuma Y 
Published: January 2022

Background and aimsThe type IV intermediate filament, nestin, may be a candidate diagnostic marker for combined hepatocellular–cholangiocarcinoma (cHCC–CCA). Therefore, the significance of nestin as a diagnostic marker for cHCC–CCA categorized by the World Health Organization (WHO) 2019 classification and its relationship with clinicopathological features were examined in the present study.Methods and resultsNestin expression was immunohistochemically assessed in the liver sections from 75 patients with cHCC–CCA, 22 with small duct‐type intrahepatic cholangiocarcinoma (iCCA), 20 with large duct‐type iCCA and 35 with hepatocellular carcinoma (HCC). Nestin expression and its relationship with clinicopathological features and genetic alterations were investigated in cHCC–CCA. Nestin expression was detected in significantly more patients with cHCC–CCA (66.7%) than in those with large duct‐type iCCA (5%) (P < 0.01), HCC (2.9%) (P < 0.01) and small duct‐type iCCA (40.9%) (P < 0.05). Nestin expression was partly associated with neural cell adhesion molecule (NCAM) and vimentin expression. Nestin expression was also observed in significantly more patients with small duct‐type iCCA than in those with large duct‐type iCCA and HCC (P < 0.01). Nestin‐positive cHCC–CCA was characterized by a smaller tumour size, the more frequent presence of cholangiolocellular carcinoma (CLC) components, a higher rate of p53 overexpression and a higher rate of multiple genetic alterations (P < 0.05). Furthermore, p53 overexpression was associated with a higher histological grade and multiple genetic alterations (P < 0.05) in nestin‐positive cHCC–CCA.ConclusionNestin may be a useful diagnostic marker for a specific subgroup of cHCC–CCA and small duct‐type iCCA associated with CLC components, p53 mutations and multiple genetic alterations, which are related to stemness and multipotent differentiation.
Direct and indirect effects of different dentifrices on the initial bacterial colonization of enamel in situ overnight
Authors: Rosenauer Tobias , Basche Sabine , Flemming Jasmin , Hannig Christian , König Belinda , Hannig Matthias 
Published: January 2022

AbstractObjectiveThe aim of this study was to investigate the direct and indirect influence of fluoridated toothpastes and fluoride‐free toothpaste with hydroxyapatite (HAP) as active ingredient on initial bacterial colonization on enamel in situ.MethodsFor this clinical‐experimental pilot study, eight subjects were instructed to brush their teeth with three different toothpastes (Elmex®: 1400 ppm AmF, Meridol®: 1400 ppm AmF +SnF2, Karex®: HAP), using each for two consecutive days. As a control, brushing without toothpaste was performed. To evaluate bacterial colonization, subject wore splints with buccally placed bovine enamel platelets overnight. Two modes were tested. In a first pass (regimen A), the splints were inserted after toothbrushing to examine the indirect effects of the dentifrices. In order to investigate the direct effects, the specimens were brushed in situ in a second pass (regimen B). Biofilm formation was visualized and quantified using fluorescence microscopy (DAPI and BacLight) and transmission electron microscopy (TEM).ResultsFor brushing regimen A (indirect effect of dentifrices), no statistical differences were detected between any of the tested dentifrices or the control. Likewise, no statistically significant differences were recorded for brushing regimen B (direct effect of dentifrices). Furthermore, no differences between the different brushing techniques were determined with regard to the ultrastructure of the overnight biofilm.ConclusionWithin the limitations of the present pilot study, it can be concluded that in patients with good oral hygiene, dentifrices and their chemical composition have no statistically significant effect on the initial bacterial colonization of enamel platelets in situ, irrespectively of the mode of application.
Present status and future directions – Guided endodontics
Authors: Connert Thomas , Weiger Roland , Krastl Gabriel 
Published: January 2022

AbstractLuxation injuries and other stimuli may lead to a pulp canal obliteration (PCO). Even though the apposition of tertiary dentine is a sign of a vital pulp, in some cases root canal treatment is indicated in the long term due to apical periodontitis or pulpitis. Depending on the extent of PCO, root canal treatment may be challenging even for experienced and well‐equipped endodontic specialists. The ‘guided endodontics’ (GE) technique was introduced 6 years ago as an alternative to conventional access cavity preparation for teeth with PCO and apical pathosis or irreversible pulpitis. Using three‐dimensional radiological imaging such as cone‐beam computed tomography and a digital surface scan, an optimal access to the orifice of the calcified root canal can be planned virtually with appropriate software. GE is implemented either with the help of templates analogous to guided implantology (= static navigation) or by means of dynamic navigation based on a camera‐marker system. GE has emerged as a field of research in the last 6 years with very promising laboratory‐based results regarding the accuracy of guided endodontic access cavities for both static and dynamic navigation. Clinical implementation seems to provide favourable results, but the evidence is mainly based on numerous case reports and a few case series. This narrative review aims to provide an update on the present status of GE and to identify relevant research areas that could contribute to further improvements of this technique.
Pulpotomy for treatment of complicated crown fractures in permanent teeth: A systematic review
Authors: Donnelly Aisling , Foschi Federico , McCabe Paul , Duncan Henry F. 
Published: January 2022

AbstractBackgroundConsensus on the treatment of choice for complicated crown fractures of teeth is limited. Recent guidance recommends vital‐pulp‐therapy; however, the preferred type is not specified. Higher success rates for pulpotomy compared to pulp‐capping have been documented, which suggests pulpotomy may be a preferable option for complicated crown‐fractures.ObjectivesThe purpose of this systematic review was to determine the success rate of pulpotomy (partial and complete) on teeth that suffered complicated crown fractures. Participants: patients who have suffered a complicated crown fracture to an anterior permanent tooth. Intervention: pulpotomy (partial or complete). Comparator: pulp‐capping or root canal treatment. Outcome: combined clinical and radiographic success at or after 12 months.MethodsA systematic literature using key search terms was conducted using PubMed, Web of Science and Cochrane‐Central‐Register‐of‐Controlled‐Trials (CENTRAL) as well as a grey literature search from inception to May 2021 and without language restricted to English. Strict inclusion criteria were applied. A standardized tool with defined criteria to assess the risk of bias in each study was used. For non‐randomized comparative trials, the Robins‐I tool was used while the Newcastle‐Ottawa scale was used for non‐comparative non‐randomized studies.ResultsSeven retrospective clinical studies were included. The studies reported high success rates for pulpotomy with overall success ranges for partial or complete pulpotomy ranging from 75% to 96%. One study compared the success rates of pulpotomy to an alternative treatment option pulp capping (90.9% vs. 67%, respectively). Due to the lack of homogeneity in the included studies, a meta‐analysis was not possible.DiscussionThis review highlights the limited evidence based for the current guidance on treatment of complicated crown fractures. The findings of the review indicate high success rates for pulpotomy; however, there is a moderate risk of bias and small sample sizes in the included studies with the result that the overall results should be interpreted with caution.ConclusionWithin the limitations of this review, the benefits and high success rates reported for partial pulpotomy suggest this procedure, rather than pulp‐capping, should be considered as the treatment of choice for both immature and mature teeth that have suffered complicated crown‐fractures.
Impact of mixed bundling type on consumers’ value perception
Authors: Li Nan , Song Jae‐Do 
Published: January 2022

AbstractA discount through bundling can harm consumers’ perception of the reference price of, and willingness to pay for, the bundled products. This study investigates how types of bundling such as mixed‐leader and mixed‐joint bundling affect the value perception of a primary product. Three experiments were developed and used to test theoretical hypotheses. Data were collected and analyzed using multivariate analyses of variance and mediation analysis with the bootstrapping procedure. Results show that leader bundling is more efficient in protecting the value perception of the primary product than joint bundling. The bundling type effect is mediated by consumers’ discount attribution and is strengthened in a low product similarity scenario. Further, cognitive style and attention level significantly mediate the relationship between product similarity and consumers’ discount attribution, especially under leader bundling. These findings provide a deeper understanding of the bundling type effect. The moderating effects of product similarity show the conditions for the bundling type effect. Additionally, the mediating effect of discount attribution is very meaningful since attribution is the most frequently mentioned theory in bundling research, while no study has directly examined it to date. The findings also provide useful implications for retailers to design efficient bundling promotion.
Experiences and challenges faced by community mental health workers when providing care to people with mental health conditions: A qualitative descriptive study
Authors: Goh Yong‐Shian , Ow Yong Qing Yun Jenna , Soo Shuenn‐Chiang , Wan Po Ching Jennie , Ng Vincent Chee Keong 
Published: January 2022

AbstractThe global prevalence of mental health conditions and the associated wide treatment gaps have led to increased demand for quality mental healthcare services. In Singapore, despite a shift towards a joint provision of mental healthcare in hospitals and the community, experiences of mental healthcare teams in such hospital‐community partnerships have remained unclear. Through a qualitative descriptive approach, this study explored community mental health workers’ experiences and perceptions of working with partners from tertiary hospitals and other community organisations. Eighteen participants were individually interviewed with a semi‐structured question guide through video conferencing. This study was guided by the 32‐item checklist from the Consolidated Criteria for Reporting Qualitative Research. Data were subjected to Braun and Clark’s six‐step thematic analysis. Three themes emerged: (i) the need for supportive partners, due to institutional and legal challenges faced in the participants’ liaison with hospital partners and other community organisations; (ii) the need for a supportive organisation, whose presence and importance were revealed by the interviews; and (iii) the necessity of advanced training, identified by the participants as a contributor to their professional growth. The findings highlighted the importance of inter‐sectoral communication and positive effects of a robust organisational support system. Accordingly, hospitals and community mental healthcare organisations should consider strengthening networking and boosting case discussions through regular inter‐sectoral meetings that would prioritise the clients’ continuity of care. Furthermore, opportunities for advanced trainings should be created for community‐based mental healthcare workers.
How to culture limnoterrestrial heterotardigrades
Authors: Momeni Sogol , Fuentes‐González Jesualdo , Pienaar Jason 
Published: January 2022

AbstractZoologists have long tried to culture the limnoterrestrial heterotardigrades associated with bryophytes and lichens without success. By carefully observing heterotardigrades in the genera Echiniscus, Pseudechiniscus, and Viridiscus over many months, we determined that these organisms feed on chloroplasts and cytoplasm from the cells of moss (typically moss protonema), and on the single‐celled green algae associated with the moss (typically Chlorella vulgaris). We also determined that the cryptogams they associate with, and hence the heterotardigrades themselves, spend more time in a dried state than do most eutardigrades, which are more easily cultured. Taking these observations into account, we varied food, water, and desiccation cycle conditions with the aim of developing a viable culturing protocol for heterotardigrades. We used this experimentally derived protocol to maintain laboratory cultures of the tardigrades Echiniscus sp., Pseudechiniscus aff. P. ramazzotti and Viridiscus viridianus, which regularly produced new eggs and hatchlings. Both moss and algae from their natural habitats were used as food sources, and a small layer of rain or spring water was added every morning and allowed to partially evaporate overnight. Furthermore, the organisms were more likely to lay eggs on a dense mat of moss protonema, grown by inserting tips of moss branches into a solidified KCM–agar medium. The medium also provided a walking substrate for the tardigrades, and possibly a source of cations. Crucially, the cultures were allowed to dry out completely every 10 days for a period of at least 3 days. Moss in the culture dish significantly improved the chances of the tardigrades coming out of their desiccation‐resistant states successfully. The ability to culture heterotardigrades makes these organisms available for modern genomics and other studies with implications for understanding desiccation resistance mechanisms beyond those studied in a few model eutardigrade species.
Analysing interactions in online discussions through social network analysis
Authors: Ye Dan , Pennisi Svoboda 
Published: January 2022

AbstractBackgroundOnline discussion is one of the commonly used tools to enhance students' interactions and engagements in online courses, but it is not clear how social presence in online discussions impacts students' learning and what kinds of interactions we should encourage. Social network analysis provides a new methodology to investigate how social interactions in online discussions influence learning.ObjectivesThe study aims to identify students' online discussion interaction patterns and investigate how they are related to students' learning performance in an asynchronous course.MethodsStudents who enrolled in an asynchronous undergraduate course were invited to participate in this study. Participants' online discussion participation data were collected from six online discussions from an asynchronous online course. Data were analysed using social network analysis methods as well as correlation and regression analysis.Results and ConclusionsWe found that statistically significant positive correlations existed between learning performance and out‐degree and closeness, respectively, which provided evidence to support that social interactions in online discussions have positive correlations with learning. We also found that out‐closeness contributes to students' learning performance. The results of the study imply that knowledge construction occurs mainly in the centre of the outgoing network. By interpreting this study's results with the social construction of knowledge model, we conclude that knowledge construction mainly happens in reading and commenting on others' posts by internalizing and integrating external useful information from others.ImplicationsWhile numerous studies have emphasized the importance of interactions in online discussions or collaborative learning, there are limited studies on what kind of interactions we should encourage and what role students play in knowledge construction. The results of this study provide evidence that knowledge construction happens when students are reading and commenting on others' posts, which includes a hidden process of integrating external useful information into their own understanding. Practical strategies are provided to encourage students to be expansive and actively reach out to other students.