bluuebunny/crossref_metadata_2025 huggingface dataset:
Long non-coding RNA LINC00930 targeting miR-6792-3p/ZBTB16 regulates the proliferation and EMT of pancreatic cancer
Authors: Mao Yingqing , Su Xian , Guo Qingsong , Yao Xihao , Zhao Qun , Guo Yibing , Wang Yao , Li Xiaohong , Lu Yuhua
Published: May 2024

Emerging evidence suggests the dysregulation of long non-coding RNAs (lncRNAs) involved in pancreatic cancer (PC). However, the function of LINC00930 in PC has not been elaborated. In this study, we found that LINC00930 was significantly down-regulated in PC cell lines and tissues, and associated with tumor size, lymphatic metastasis, TNM stage and poor prognosis. According to the bioinformatics database, the downregulation of LINC00930 was a common event in PC associated with prognosis and EMT. Overexpression of LINC00930 inhibited the aggressive cancer phenotypes including proliferation, metastasis and epithelial-mesenchymal transition (EMT) of PC in vitro and in vivo. Bioinformatics and dual-luciferase reporter assay indicated that miR-6792-3p could directly bind to LINC00930. Additionally, the Zinc finger and BTB domain containing 16 (ZBTB16) was significantly declined in PC, which was predicted to be the downstream gene of miR-6792-3p. MiR-6792-3p mimic rescued the decreased proliferation, metastasis and EMT caused by ZBTB16 in PC cells. The LINC00930/miR-6792-3p/ZBTB16 axis was associated with the malignant progression and process of PC. The relative expression of LINC00930 was negatively correlated with the expression of miR-6792-3p and was closely linked with ZBTB16 levels in PC. LINC00930 might serve as a potential prognostic biomarker and therapeutic target for PC.
A case-control study of the risk factors for fistula-in-ano in infants and toddlers
Authors: Sun Yanting , Liang Hongtao , Hao Shuang , Yin Lu , Pan Yibin , Wang Chen , Lu Jingen
Published: May 2024

Background

Limited data are available regarding the risk factors for fistula-in-ano (FIA) in infants and toddlers, potentially affecting their daily lives.

Objectives

The purpose of this study was to identify potential risk factors for FIA in infants and toddlers, in order to implement early preventive interventions, avoid disease progression, and develop therapeutic strategies.

Design and settings

A retrospective case-control study was conducted, comparing 41 infants and toddlers diagnosed with FIA with 41 healthy controls, between August 2020 and December 2021.

Independent variables

(a) maternal characteristics during pregnancy and delivery, (b) perinatal characteristics, dietary behaviors, and defecation-related behaviors in infants and toddlers, (c) family dietary behaviors.

Results

Mothers of infants and toddlers with FIA had given birth more times in the past, while the infants and toddlers themselves had less mealtime, a higher rate of exclusive breastfeeding, frequent loose stools, and a larger proportion of used wipes, experiencing perianal skin anomalies. The logistic regression analysis revealed that there are four significant risk factors associated with the development of FIA in infants and toddlers, including the number of previous deliveries by the mother (OR 6.327), defecation frequency score (OR 5.351), stool consistency score (OR 5.017), and cleaning with wipes after defecation (OR 8.089).

Conclusion

Based on our data, it appeared that FIA in infants and toddlers could be attributed to several factors. These included an increased number of previous deliveries by mothers, frequent loose stools, and repeated wipe use. To prevent the occurrence and worsening of the disease, it is important to improve the frequency and consistency of stooling and provide proper care. Further research is required to verify these findings in other clinical settings.
Computer-based facial recognition as an assisting diagnostic tool to identify children with Noonan syndrome
Authors: Huang Yulu , Sun Haomiao , Chen Qinchang , Shen Junjun , Han Jin , Shan Shiguang , Wang Shushui
Published: May 2024

Background

Noonan syndrome (NS) is a rare genetic disease, and patients who suffer from it exhibit a facial morphology that is characterized by a high forehead, hypertelorism, ptosis, inner epicanthal folds, down-slanting palpebral fissures, a highly arched palate, a round nasal tip, and posteriorly rotated ears. Facial analysis technology has recently been applied to identify many genetic syndromes (GSs). However, few studies have investigated the identification of NS based on the facial features of the subjects.

Objectives

This study develops advanced models to enhance the accuracy of diagnosis of NS.

Methods

A total of 1,892 people were enrolled in this study, including 233 patients with NS, 863 patients with other GSs, and 796 healthy children. We took one to 10 frontal photos of each subject to build a dataset, and then applied the multi-task convolutional neural network (MTCNN) for data pre-processing to generate standardized outputs with five crucial facial landmarks. The ImageNet dataset was used to pre-train the network so that it could capture generalizable features and minimize data wastage. We subsequently constructed seven models for facial identification based on the VGG16, VGG19, VGG16-BN, VGG19-BN, ResNet50, MobileNet-V2, and squeeze-and-excitation network (SENet) architectures. The identification performance of seven models was evaluated and compared with that of six physicians.

Results

All models exhibited a high accuracy, precision, and specificity in recognizing NS patients. The VGG19-BN model delivered the best overall performance, with an accuracy of 93.76%, precision of 91.40%, specificity of 98.73%, and F1 score of 78.34%. The VGG16-BN model achieved the highest AUC value of 0.9787, while all models based on VGG architectures were superior to the others on the whole. The highest scores of six physicians in terms of accuracy, precision, specificity, and the F1 score were 74.00%, 75.00%, 88.33%, and 61.76%, respectively. The performance of each model of facial recognition was superior to that of the best physician on all metrics.

Conclusion

Models of computer-assisted facial recognition can improve the rate of diagnosis of NS. The models based on VGG19-BN and VGG16-BN can play an important role in diagnosing NS in clinical practice.
Development of the entrustable professional activity ‘medication reconciliation’ for clinical pharmacy
Authors: Bozic Ula , Witti Matthias J. , Ralf Schmidmaier , Fischer Martin R. , Zottmann Jan M. , Pudritz Yvonne M.
Published: May 2024

Background

Entrustable professional activities (EPAs) are observable process descriptions of clinical work units. EPAs support learners and tutors in assessment within healthcare settings. For use amongst our pharmacy students as well as pre-registration pharmacists we wanted to develop and validate an EPA for use in a clinical pharmacy setting at LMU University Hospital.

Methods

The development of the clinical pharmacy EPA followed a set pathway. A rapid literature review informed the first draft, an interprofessional consensus group consisting of pharmacists, nurses, and medical doctors refined this draft. The refined version was then validated via online survey utilising clinical pharmacists from Germany.

Results

We designed, refined and validated an EPA regarding medication reconciliation for assessment of pharmacy students and trainees within the pharmacy department at LMU University Hospital in Munich. Along with the EPA description an associated checklist to support the entrustment decision was created. For validation an online survey with 27 clinical pharmacists from all over Germany was conducted. Quality testing with the EQual rubric showed a good EPA quality.

Conclusions

We developed the first clinical pharmacy EPA for use in a German context. Medication reconciliation is a suitable EPA candidate as it describes a clinical activity performed by pharmacists in many clinical settings. The newly developed and validated EPA ‘Medication Reconciliation’ will be used to assess pharmacy students and trainees.
Question banks: credit? Or debit? A qualitative exploration of their use among medical students
Authors: Fisher James , Leahy Declan , Lim Jun Jie , Astles Emily , Salvatore Jacobo , Thomson Richard
Published: May 2024

Background

Online question banks are the most widely used education resource amongst medical students. Despite this there is an absence of literature outlining how and why they are used by students. Drawing on Deci and Ryan’s self-determination theory, our study aimed to explore why and how early-stage medical students use question banks in their learning and revision strategies.

Methods

The study was conducted at Newcastle University Medical School (United Kingdom and Malaysia). Purposive, convenience and snowball sampling of year two students were employed. Ten interviews were conducted. Thematic analysis was undertaken iteratively, enabling exploration of nascent themes. Data collection ceased when no new perspectives were identified.

Results

Students’ motivation to use question banks was predominantly driven by extrinsic motivators, with high-stakes exams and fear of failure being central. Their convenience and perceived efficiency promoted autonomy and thus motivation. Rapid feedback cycles and design features consistent with gamification were deterrents to intrinsic motivation. Potentially detrimental patterns of question bank use were evident: cueing, avoidance and memorising. Scepticism regarding veracity of question bank content was absent.

Conclusions

We call on educators to provide students with guidance about potential pitfalls associated with question banks and to reflect on potential inequity of access to these resources.
The mediating effect of pregnancy adaptation between family support and maternal-fetal bonding: a cross-sectional study
Authors: Wu Wan-Ru , Lee Li-Chun , Hung Chich-Hsiu , Huang Hui-Chuan
Published: May 2024

Background

Establishing a nurturing bond with the unborn child is essential for expectant mothers throughout pregnancy. While the influence of family support and pregnancy adaptation on maternal-fetal bonding is evident, these factors remain unexplored in the early stages of pregnancy. This study aims to elucidate the dynamic interaction between family support, pregnancy adaptation, and maternal-fetal bonding during the first trimester, explicitly investigating the mediating role of pregnancy adaptation.

Method

A cross-sectional design was conducted to recruit expectant mothers between 8 and 12 weeks of gestation without significant complications.

Results

Family support and pregnancy adaptation emerged as significant predictors of maternal-fetal bonding, and pregnancy adaptation mediated the relationship between family support and maternal-fetal bonding in the first trimester.

Conclusions

The study confirms the critical role of family support and pregnancy adaptation in facilitating maternal-fetal bonding during early pregnancy, with pregnancy adaptation fully mediating this relationship. Healthcare providers are encouraged to involve family members in early interventions, focusing on assessing family support and engaging them in education and activities to strengthen the emotional bond between the mother and her unborn child.
Quasi-static mechanical evaluation of canine cementless total hip replacement broaches: effect of tooth design on broach and stem insertion
Authors: Lawson Zachary T. , Hollenbeck Danielle L. , Silveira Catrina J. , Moreno Michael R. , Robbins Andrew B. , Saunders W. Brian
Published: May 2024

Background

Biomedtrix BFX® cementless total hip replacement (THR) requires the use of femoral broaches to prepare a press-fit envelope within the femur for subsequent stem insertion. Current broaches contain teeth that crush and remove cancellous bone; however, they are not particularly well-suited for broaching sclerotic (corticalized) cancellous bone. In this study, three tooth designs [Control, TG1 (additional V-grooves), TG2 (diamond tooth pattern)] were evaluated with a quasi-static testing protocol and polyurethane test blocks simulating normal and sclerotic bone. To mimic clinical broaching, a series of five sequential broach insertions were used to determine cumulative broaching energy (J) and peak loads during broach insertion. To determine the effect of broach tooth design on THR stem insertion, a BFX® stem was inserted into prepared test blocks and insertion and subsidence energy and peak loads were determined.

Results

Broach tooth design led to significant differences in broaching energy and peak broaching loads in test blocks of both densities. In low density test blocks, TG1 required the lowest cumulative broaching energy (10.76 ±0.29 J), followed by Control (12.18 ±1.20 J) and TG2 (16.66 ±0.78 J) broaches. In high density test blocks, TG1 required the lowest cumulative broaching energy (32.60 ±2.54 J) as compared to Control (33.25 ±2.16 J) and TG2 (59.97 ±3.07 J).  During stem insertion and subsidence testing, stem insertion energy for high density test blocks prepared with Control broaches was 14.53 ± 0.81 J, which was significantly lower than blocks prepared with TG1 (22.53 ± 1.04 J) or TG2 (19.38 ± 3.00 J) broaches. For stem subsidence testing in high density blocks, TG1 prepared blocks required the highest amount of energy to undergo subsidence (14.49 ± 0.49 J), which was significantly greater than test blocks prepared with Control (11.09 ±0.09 J) or TG2 (12.57 ± 0.81 J) broaches.

Conclusions

The additional V-grooves in TG1 broaches demonstrated improved broaching performance while also generating press-fit envelopes that were more resistant to stem insertion and subsidence. TG1 broaches may prove useful in the clinical setting; however additional studies that more closely simulate clinical broach impaction are necessary prior to making widespread changes to THR broaches.
Gastric emphysema and pneumatosis intestinalis in two common marmosets with duodenal dilation syndrome
Authors: Kawarai Shinpei , Sakai Yasuhiro , Iriki Atsushi , Yamazaki Yumiko
Published: May 2024

Background

Common marmosets (Callithrix jacchus) are widely used as primate experimental models in biomedical research. Duodenal dilation with chronic vomiting in captive common marmosets is a recently described life-threatening syndrome that is problematic for health control. However, the pathogenesis and cause of death are not fully understood.

Case presentation

We report two novel necropsy cases in which captive common marmosets were histopathologically diagnosed with gastric emphysema (GE) and pneumatosis intestinalis (PI). Marmoset duodenal dilation syndrome was confirmed in each case by clinical observation of chronic vomiting and by gross necropsy findings showing a dilated, gas-filled and fluid-filled descending duodenum that adhered to the ascending colon. A diagnosis of GE and PI was made on the basis of the bubble-like morphology of the gastric and intestinal mucosa, with histological examination revealing numerous vacuoles diffused throughout the lamina propria mucosae and submucosa. Immunostaining for prospero homeobox 1 and CD31 distinguished gas cysts from blood and lymph vessels. The presence of hepatic portal venous gas in case 1 and possible secondary bacteremia-related septic shock in case 2 were suggested to be acute life-threatening abdominal processes resulting from gastric emphysema and pneumatosis intestinalis.

Conclusions

In both cases, the gross and histopathological findings of gas cysts in the GI tract walls matched the features of human GE and PI. These findings contribute to clarifying the cause of death in captive marmosets that have died of gastrointestinal diseases.
Synergistic effects of Smac mimetic APG-1387 with anti-PD-1 antibody are attributed to increased CD3 + NK1.1 + cell recruitment secondary to induction of cytokines from tumor cells
Authors: Pan Wentao , Luo Qiuyun , Liang Eric , Shi Mude , Sun Jian , Shen Huimin , Lu Zhenhai , Zhang Lin , Yan Xianglei , Yuan Luping , Zhou Suna , Yi Hanjie , Zhai Yifan , Qiu Miao-zhen , Yang Dajun
Published: May 2024

Background

Immune checkpoint inhibitors are approved for the treatment of various tumors, but the response rate is not satisfactory in certain malignancies. Inhibitor of apoptosis proteins (IAP) ubiquitin-E3 ligase activity is involved in the regulation of immune responses. APG-1387 is a novel second mitochondria-derived activator of caspase (Smac) mimetic IAP inhibitor. The aim of this study was to explore the synergistic effect of APG-1387 when combined with anti-PD-1 antibody in a preclinical setting.

Methods

We utilized syngeneic mouse models of ovarian cancer (ID8), colon cancer (MC38), malignant melanoma (B16), and liver cancer (Hepa1-6) to assess the combination effect of APG-1387 and anti-PD-1 antibody, including immune-related factors, tumor growth, and survival. MSD V-PLEX validated assays were used to measure in vitro and in vivo cytokine release.

Results

In ID8 ovarian cancer and MC38 colon cancer models, APG-1387 and anti-PD1 antibody had synergistic antitumor effects. In the MC38 model, the combination of APG-1387 and anti-PD-1 antibody significantly inhibited tumor growth (P < 0.0001) and increased the survival rate of tumor-bearing animals (P < 0.001). Moreover, we found that APG-1387 upregulated tumor-infiltrating CD3 + NK1.1 + cells by nearly 2-fold, by promoting tumor cell secretion of IL-12. Blocking IL-12 secretion abrogated the synergistic effects of APG-1387 and anti-PD-1 antibody in both MC38 and ID8 models.

Conclusions

APG-1387 has the potential to turn “cold tumors” into hot ones by recruiting more CD3 + NK1.1 + cells into certain tumors. Based on these and other data, the safety and therapeutic effect of this combination will be investigated in a phase 1/2 trial in patients with advanced solid tumors or hematologic malignancies (NCT03386526).

Graphic abstract
Emergence of extensive drug resistance and high prevalence of multidrug resistance among clinical Proteus mirabilis isolates in Egypt
Authors: ElTaweel Maggi , Said Heba Shehta , Barwa Rasha
Published: May 2024

Background

Proteus mirabilis is an opportunistic pathogen that has been held responsible for numerous nosocomial and community-acquired infections which are difficult to be controlled because of its diverse antimicrobial resistance mechanisms.

Methods

Antimicrobial susceptibility patterns of P. mirabilis isolates collected from different clinical sources in Mansoura University Hospitals, Egypt was determined. Moreover, the underlying resistance mechanisms and genetic relatedness between isolates were investigated.

Results

Antimicrobial susceptibility testing indicated elevated levels of resistance to different classes of antimicrobials among the tested P. mirabilis clinical isolates (n = 66). ERIC-PCR showed great diversity among the tested isolates. Six isolates (9.1%) were XDR while all the remaining isolates were MDR. ESBLs and AmpCs were detected in 57.6% and 21.2% of the isolates, respectively, where blaTEM, blaSHV, blaCTX−M, blaCIT−M and blaAmpC were detected. Carbapenemases and MBLs were detected in 10.6 and 9.1% of the isolates, respectively, where blaOXA−48 and blaNDM−1 genes were detected. Quinolone resistant isolates (75.8%) harbored acc(6')-Ib-cr, qnrD, qnrA, and qnrS genes. Resistance to aminoglycosides, trimethoprim-sulfamethoxazole and chloramphenicol exceeded 80%. Fosfomycin was the most active drug against the tested isolates as only 22.7% were resistant. Class I or II integrons were detected in 86.4% of the isolates. Among class I integron positive isolates, four different gene cassette arrays (dfrA17- aadA5, aadB-aadA2, aadA2-lnuF, and dfrA14-arr-3-blaOXA−10-aadA15) and two gene cassettes (dfrA7 and aadA1) were detected. While class II integron positive isolates carried four different gene cassette arrays (dfrA1-sat1-aadA1, estXVr-sat2-aadA1, lnuF- dfrA1-aadA1, and dfrA1-sat2).

Conclusion

P. Mirabilis ability to acquire resistance determinants via integrons may be held responsible for the elevated rates of antimicrobial resistance and emergence of XDR or even PDR strains limiting the available therapeutic options for management of infections caused by those strains.
Enhancing intraneural revascularization following peripheral nerve injury through hypoxic Schwann-cell-derived exosomes: an insight into endothelial glycolysis
Authors: Sun Jun , Zeng Qiuhua , Wu Zhimin , Li Zhangyu , Gao Qun , Liao Zhi , Li Hao , Ling Cong , Chen Chuan , Wang Hui , Zhang Baoyu
Published: May 2024

Background

Endothelial cell (EC)-driven intraneural revascularization (INRV) and Schwann cells-derived exosomes (SCs-Exos) both play crucial roles in peripheral nerve injury (PNI). However, the interplay between them remains unclear. We aimed to elucidate the effects and underlying mechanisms of SCs-Exos on INRV following PNI.

Results

We found that GW4869 inhibited INRV, as well as that normoxic SCs-Exos (N-SCs-Exos) exhibited significant pro-INRV effects in vivo and in vitro that were potentiated by hypoxic SCs-Exos (H-SCs-Exos). Upregulation of glycolysis emerged as a pivotal factor for INRV after PNI, as evidenced by the observation that 3PO administration, a glycolytic inhibitor, inhibited the INRV process in vivo and in vitro. H-SCs-Exos more significantly enhanced extracellular acidification rate/oxygen consumption rate ratio, lactate production, and glycolytic gene expression while simultaneously suppressing acetyl-CoA production and pyruvate dehydrogenase E1 subunit alpha (PDH-E1α) expression than N-SCs-Exos both in vivo and in vitro. Furthermore, we determined that H-SCs-Exos were more enriched with miR-21-5p than N-SCs-Exos. Knockdown of miR-21-5p significantly attenuated the pro-glycolysis and pro-INRV effects of H-SCs-Exos. Mechanistically, miR-21-5p orchestrated EC metabolism in favor of glycolysis by targeting von Hippel-Lindau/hypoxia-inducible factor-1α and PDH-E1α, thereby enhancing hypoxia-inducible factor-1α-mediated glycolysis and inhibiting PDH-E1α-mediated oxidative phosphorylation.

Conclusion

This study unveiled a novel intrinsic mechanism of pro-INRV after PNI, providing a promising therapeutic target for post-injury peripheral nerve regeneration and repair.

Graphical Abstract
Efficacy and safety of autologous or allogeneic mesenchymal stromal cells from adult adipose tissue expanded and combined with tricalcium phosphate biomaterial for the surgical treatment of atrophic nonunion of long bones: a phase II clinical trial
Authors: Orozco Delclós Lluís , Soler Rich Robert , Arriaza Loureda Rafael , Moreno García Alonso , Gómez Barrena Enrique
Published: May 2024

Background

Autologous bone grafting is the standard treatment for the surgical management of atrophic nonunion of long bones. Other solutions, such as bone marrow mesenchymal stem cells (BM-MSC) combined with phospho-calcium material, have also been used. Here we evaluate the safety and early efficacy of a novel procedure using autologous or allogenic adipose tissue mesenchymal stromal cells (AT-MSC) seeded in a patented tricalcium phosphate-based biomaterial for the treatment of bone regeneration in cases of atrophic nonunion.

Methods

This was a prospective, multicentric, open-label, phase 2 clinical trial of patients with atrophic nonunion of long bones. Biografts of autologous or allogenic AT-MSC combined with a phosphate substrate were manufactured prior to the surgical procedures. The primary efficacy was measured 6 months after surgery, but patients were followed for 12 months after surgery and a further year out of the scope of the study. All adverse events were recorded. This cohort was compared with a historical cohort of 14 cases treated by the same research team with autologous BM-MSC.

Results

A total of 12 patients with atrophic nonunion of long bones were included. The mean (SD) age was 41.2 (12.1) years and 66.7% were men. Bone healing was achieved in 10 of the 12 cases (83%) treated with the AT-MSC biografts, a percentage of healing similar (11 of the 14 cases, 79%) to that achieved in patients treated with autologous BM-MSC. Overall, two adverse events, in the same patient, were considered related to the procedure.

Conclusions

The results of this study suggest that AT-MSC biografts are safe for the treatment of bone regeneration in cases of atrophic nonunion and reach high healing rates.

Trial registration

Study registered with EUDRA-CT (2013-000930-37) and ClinicalTrials.gov (NCT02483364).
The biological function of the N6-Methyladenosine reader YTHDC2 and its role in diseases
Authors: Wu Xudong , Chen Hui , Li Kai , Zhang Hong , Li Kai , Tan Haoyu
Published: May 2024

N6-methyladenosine (m6A) stands as the most prevalent modified form of RNA in eukaryotes, pivotal in various biological processes such as regulating RNA stability, translation, and transcription. All members within the YT521-B homology (YTH) gene family are categorized as m6A reading proteins, capable of identifying and binding m6A modifications on RNA, thereby regulating RNA metabolism and functioning across diverse physiological processes. YTH domain-containing 2 (YTHDC2), identified as the latest member of the YTH family, has only recently started to emerge for its biological function. Numerous studies have underscored the significance of YTHDC2 in human physiology, highlighting its involvement in both tumor progression and non-tumor diseases. Consequently, this review aims to further elucidate the pathological mechanisms of YTHDC2 by summarizing its functions and roles in tumors and other diseases, with a particular focus on its downstream molecular targets and signaling pathways.
The effect of audit and feedback and implementation support on guideline adherence and patient outcomes in cardiac rehabilitation: a study protocol for an open-label cluster-randomized effectiveness-implementation hybrid trial
Authors: Michelsen Halldóra Ögmundsdóttir , Lidin Matthias , Bäck Maria , Duncan Therese Scott , Ekman Björn , Hagström Emil , Hägglund Maria , Lindahl Bertil , Schlyter Mona , Leósdóttir Margrét
Published: May 2024

Background

Providing secondary prevention through structured and comprehensive cardiac rehabilitation programmes to patients after a myocardial infarction (MI) reduces mortality and morbidity and improves health-related quality of life. Cardiac rehabilitation has the highest recommendation in current guidelines. While treatment target attainment rates at Swedish cardiac rehabilitation centres is among the highest in Europe, there are considerable differences in service delivery and variations in patient-level outcomes between centres. In this trial, we aim to study whether centre-level guideline adherence and patient-level outcomes across Swedish cardiac rehabilitation centres can be improved through a) regular audit and feedback of cardiac rehabilitation structure and processes through a national quality registry and b) supporting cardiac rehabilitation centres in implementing guidelines on secondary prevention. Furthermore, we aim to evaluate the implementation process and costs.

Methods

The study is an open-label cluster-randomized effectiveness-implementation hybrid trial including all 78 cardiac rehabilitation centres (attending to approximately 10 000 MI patients/year) that report to the SWEDEHEART registry. The centres will be randomized 1:1:1 to three clusters: 1) reporting cardiac rehabilitation structure and process variables to SWEDEHEART every six months (audit intervention) and being offered implementation support to implement guidelines on secondary prevention (implementation support intervention); 2) audit intervention only; or 3) no intervention offered. Baseline cardiac rehabilitation structure and process variables will be collected. The primary outcome is an adherence score measuring centre-level adherence to secondary prevention guidelines. Secondary outcomes include patient-level secondary prevention risk factor goal attainment at one-year after MI and major adverse coronary outcomes for up to five-years post-MI. Implementation outcomes include barriers and facilitators to guideline adherence evaluated using semi-structured focus-group interviews and relevant questionnaires, as well as costs and cost-effectiveness assessed by a comparative health economic evaluation.

Discussion

Optimizing cardiac rehabilitation centres’ delivery of services to meet standards set in guidelines may lead to improvement in cardiovascular risk factors, including lifestyle factors, and ultimately a decrease in morbidity and mortality after MI.

Trial registration

ClinicalTrials.gov. Identifier: NCT05889416. Registered 2023-03-23.
Diagnostic yield of exome and genome sequencing after non-diagnostic multi-gene panels in patients with single-system diseases
Authors: Wilke Matheus V. M. B. , Klee Eric W. , Dhamija Radhika , Fervenza Fernando C. , Thomas Brittany , Leung Nelson , Hogan Marie C. , Hager Megan M. , Kolbert Kayla J. , Kemppainen Jennifer L. , Loftus Elle C. , Leitzen Katie M. , Vitek Carolyn R. , McAllister Tammy , Lazaridis Konstantinos N. , Pinto e Vairo Filippo
Published: May 2024

Background

Though next-generation sequencing (NGS) tests like exome sequencing (ES), genome sequencing (GS), and panels derived from exome and genome data (EGBP) are effective for rare diseases, the ideal diagnostic approach is debated. Limited research has explored reanalyzing raw ES and GS data post-negative EGBP results for diagnostics. Results: We analyzed complete ES/GS raw sequencing data from Mayo Clinic's Program for Rare and Undiagnosed Diseases (PRaUD) patients to assess whether supplementary findings could augment diagnostic yield. ES data from 80 patients (59 adults) and GS data from 20 patients (10 adults), averaging 43 years in age, were analyzed. Most patients had renal (n=44) and auto-inflammatory (n=29) phenotypes. Ninety-six cases had negative findings and in four cases additional genetic variants were found, including a variant related to a recently described disease (RRAGD-related hypomagnesemia), a variant missed due to discordant inheritance pattern (COL4A3), a variant with high allelic frequency (NPHS2) in the general population, and a variant associated with an initially untargeted phenotype (HNF1A). Conclusion: ES and GS show diagnostic yields comparable to EGBP for single-system diseases. However, EGBP's limitations in detecting new disease-associated genes underscore the necessity for periodic updates.
Cartoon copyright recognition method based on character personality action
Authors: Li De , Wang Lingyu , Jin Xun
Published: May 2024

Aiming at the problem of cartoon piracy and plagiarism, this paper proposes a method of cartoon copyright recognition based on character personality actions. This method can be used to compare the original cartoon actions with the action characteristics of pirated or copied cartoons to identify whether there is piracy or plagiarism. Firstly, an image preprocessing scheme for character extraction is designed. GrabCut interactive image segmentation algorithm was used to obtain cartoon characters, and then binarization and morphological processing were performed on the results. Secondly, a feature extraction scheme based on character profile, moving character and character pose is designed. By extracting the perimeter and area of the character contour, the length-to-width ratio of the smallest rectangle and the inclination angle of the contour, the character contour features are obtained. The three-dimensional coordinates are established by the central point position of the cartoon character in the two-dimensional image and the change of the character's zoom in and out, and the character's motion angle characteristics are calculated. By skeletonizing a character to obtain the pose characteristics, and using deburring operation to remove redundant branches, then extract the skeleton joint angle information. Finally, feature fusion is performed on the extracted features. The experimental results show that the proposed method breaks the limitation of the conventional single feature based recognition, and can better extract the character features including contour feature, motion feature and pose feature through multi-feature based extraction, so as to protect the cartoon copyright.
SOFA in sepsis: with or without GCS
Authors: Wang Lu , Ma Xudong , Zhou Guanghua , Gao Sifa , Pan Wei , Chen Jieqing , Su Longxiang , He Huaiwu , Long Yun , Yin Zhi , Shu Ting , Zhou Xiang ,   China National Critical Care Quality Control Centre Group (China-NCCQC), Liu Yongjun , Kang Yan , Yan Jing , Chen Erzhen , Xiong Bin , Qin Bingyu , Qian Kejian , Fang Wei , Zhao Mingyan , Ma Xiaochun , Yu Xiangyou , Lin Jiandong , Yang Yi , Shen Feng , Li Shusheng , Zhang Lina , Wu Weidong , Duan Meili , Wan Linjun , Yang Xiaojun , Liu Jian , Wang Zhen , Xu Lei , Hu Zhenjie , Yang Congshan
Published: May 2024

Purpose

Sepsis is a global public health burden. The sequential organ failure assessment (SOFA) is the most commonly used scoring system for diagnosing sepsis and assessing severity. Due to the widespread use of endotracheal intubation and sedative medications in sepsis, the accuracy of the Glasgow Coma Score (GCS) is the lowest in SOFA. We designed this multicenter, cross-sectional study to investigate the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis.

Methods

First, 3048 patients with sepsis admitted to Peking Union Medical College Hospital (PUMCH) were enrolled in this survey. The data were collected from June 8, 2013 to October 12, 2022. Second, 18,108 patients with sepsis in the eICU database were enrolled. Third, 2397 septic patients with respiratory system ≥ 3 points in SOFA in the eICU database were included. We investigated the predictive efficiency of SOFA with or without GCS on ICU mortality in patients with sepsis in various ICUs of PUMCH, and then we validated the results in the eICU database.

Main results

In data of ICUs in PUMCH, the predictive efficiency of SOFA without GCS (AUROC [95% CI], 24 h, 0.724 [0.688, 0.760], 48 h, 0.734 [0.699, 0.769], 72 h, 0.748 [0.713, 0.783], 168 h, 0.781 [0.747, 0.815]) was higher than that of SOFA with GCS (AUROC [95% CI], 24 h, 0.708 [0.672, 0.744], 48 h, 0.721 [0.685, 0.757], 72 h, 0.735 [0.700, 0.757], 168 h, 0.770 [0.736, 0.804]) on ICU mortality in patients with sepsis, and the difference was statistically significant (P value, 24 h, 0.001, 48 h, 0.003, 72 h, 0.004, 168 h, 0.005). In septic patients with respiratory system ≥ 3 points in SOFA in the eICU database, although the difference was not statistically significant (P value, 24 h, 0.148, 48 h, 0.178, 72 h, 0.132, 168 h, 0.790), SOFA without GCS (AUROC [95% CI], 24 h, 0.601 [0.576, 0.626], 48 h, 0.625 [0.601, 0.649], 72 h, 0.639 [0.615, 0.663], 168 h, 0.653 [0.629, 0.677]) had a higher predictive efficiency on ICU mortality than SOFA with GCS (AUROC [95% CI], 24 h, 0.591 [0.566, 0.616], 48 h, 0.616 [0.592, 0.640], 72 h, 0.628 [0.604, 0.652], 168 h, 0.651 [0.627, 0.675]).

Conclusions

In severe sepsis, it is realistic and feasible to discontinue the routine GCS for SOFA in patients with a respiratory system ≥ 3 points, and even better predict ICU mortality.
Tibiofemoral articulation and axial tibial rotation of the knee after a cruciate retaining total knee arthroplasty
Authors: Li Guoan , Zhou Chaochao , Li Sophia , Yu Jia , Foster Timothy , Bedair Hany
Published: May 2024

Purpose

Numerous research has reported that total knee arthroplasty (TKA) cannot reproduce axial tibial rotations of normal knees. The objective of this study was to measure the tibiofemoral articular contact motions and axial tibial rotations of TKA knees to investigate the mechanism causing the knee kinematics change of after TKAs.

Methods

Eleven patients with unilateral cruciate retaining (CR) TKA were tested for measurements of knee motion during a weight-bearing flexion from 0° to 105° using an imaging technique. The tibiofemoral contact kinematics were determined using the contact points on medial and lateral surfaces of the tibia and femoral condyles. Axial tibial rotations were calculated using the differences between the medial and lateral articulation distances on the femoral condyles and tibial surfaces at each flexion interval of 15°.

Results

On femoral condyles, articular contact distances are consistently longer on the medial than on the lateral sides (p < 0.05) up to 60° of flexion, corresponding to internal tibial rotations (e.g., 1.3° ± 1.0° at 15–30° interval). On tibial surfaces, the articular contact point on the medial side moved more posteriorly than on the lateral side at low flexion angles, corresponding to external tibial rotations (e.g., −1.4° ± 1.8° at 15–30° interval); and more anteriorly than on the lateral sides at mid-range flexion, corresponding to internal tibial rotations (e.g., 0.8° ± 1.7° at 45–60° interval). At higher flexion, articular motions on both femoral condyles and tibial surfaces caused minimal changes in tibial rotations.

Conclusions

These results indicate that the axial tibial rotations of these TKA knees were mainly attributed to asymmetric articulations on the medial and lateral femoral condyles and tibial surfaces. The data can help understand the mechanisms causing axial tibial rotations of TKA knees and help improve implant designs for restoration of normal knee kinematics.
Balancing Hormone Therapy: Mitigating Adverse Effects of Androgen-Deprivation Therapy and Exploring Alternatives in Prostate Cancer Management
Authors: Gudenkauf Lisa M. , Gray Struan , Gonzalez Brian D. , Sachdeva Ashwin , Autio Karen
Published: May 2024

Androgen-deprivation therapy (ADT) is well established as the standard of care in metastatic prostate cancer (PCa) management; however, ADT has significant adverse effects (AEs) that must be addressed. This review aims to highlight opportunities to mitigate AEs of ADT and explore alternatives in PCa management. Specifically, we discuss behavioral and pharmacologic strategies for mitigating ADT AEs as well as ADT-sparing approaches for hormone-sensitive and castration-resistant PCa. Equipped with effective mitigation strategies and possible alternatives, clinicians and researchers can optimize health-related quality of life for patients currently receiving ADT for PCa and consider treatments that spare patients from AEs of ADT.
Effects of Tirzepatide vs Semaglutide on β-Cell Function, Insulin Sensitivity, and Glucose Control During a Meal Test
Authors: Mather Kieren J , Mari Andrea , Heise Tim , DeVries J Hans , Hua Ming , Urva Shweta , Coskun Tamer , Haupt Axel , Heine Robert J , Pratt Edward , Thomas Melissa K , Milicevic Zvonko
Published: May 2024

Context

In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood.

Objective

This work aimed to evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data.

Methods

A 28-week double–blind, randomized, placebo-controlled trial of patients with type 2 diabetes treated with metformin was conducted at 2 clinical research centers in Germany. Interventions included tirzepatide 15 mg, semaglutide 1 mg, and placebo. Main outcome measures included glycemic control, model-derived β-cell function indices including insulin secretion rate (ISR) at 7.2–mmol/L glucose (ISR7.2), β-cell glucose sensitivity (β-CGS), insulin sensitivity, and estimated hepatic insulin-to-glucagon ratio.

Results

Tirzepatide significantly reduced fasting glucose and MMTT total glucose area under the curve (AUC) vs semaglutide (P < .01). Incremental glucose AUC did not differ significantly between treatments; therefore, greater total glucose AUC reduction with tirzepatide was mainly attributable to greater suppression of fasting glucose. A greater reduction in total ISR AUC was achieved with tirzepatide vs semaglutide (P < .01), in the context of greater improvement in insulin sensitivity with tirzepatide (P < .01). ISR7.2 was significantly increased with tirzepatide vs semaglutide (P < .05), showing improved β-CGS. MMTT-derived β-CGS was increased but not significantly different between treatments. Both treatments reduced fasting glucagon and total glucagon AUC, with glucagon AUC significantly reduced with tirzepatide vs semaglutide (P < .01). The estimated hepatic insulin-to-glucagon ratio did not change substantially with either treatment.

Conclusion

These results suggest that the greater glycemic control observed for tirzepatide manifests as improved fasting glucose and glucose excursion control, due to improvements in ISR, insulin sensitivity, and glucagon suppression.
“A Story We're Telling”
Authors: Luckert Erika
Published: May 2024

This essay suggests that our understanding of writing workshop pedagogy has been limited by a divide between composition and creative writing, and by the ways we've narrated this pedagogy in our respective fields, leaving us with little knowledge of what actually happens in writing workshops. To open new possibilities within workshop pedagogy, the author argues, we need to tell our workshop stories differently: not as method or myth, but as a complex classroom scene.
Minorities Face Delays to Pancreatic Cancer Treatment Regardless of Diagnosis Setting
Authors: Fallon John , Standring Oliver , Vithlani Nandan , Demyan Lyudmyla , Shah Manav , Gazzara Emma , Hartman Sarah , Pasha Shamsher , King Daniel A. , Herman Joseph M. , Weiss Matthew J. , DePeralta Danielle , Deutsch Gary
Published: May 2024

Introduction

Our analysis was designed to characterize the demographics and disparities between the diagnosis of pancreas cancer during emergency presentation (EP) and the outpatient setting (OP) and to see the impact of our institutions pancreatic multidisciplinary clinic (PMDC) on these disparities.

Methods

Institutional review board-approved retrospective review of our institutional cancer registry and PMDC databases identified patients diagnosed/treated for pancreatic ductal adenocarcinoma between 2014 and 2022. Chi-square tests were used for categorical variables, and one-way ANOVA with a Bonferroni correction was used for continuous variables. Statistical significance was set at p < 0.05.

Results

A total of 286 patients met inclusion criteria. Eighty-nine patients (31.1%) were underrepresented minorities (URM). Fifty-seven (64.0%) URMs presented during an EP versus 100 (50.8%) non-URMs (p = 0.037). Forty-one (46.1%) URMs were reviewed at PMDC versus 71 (36.0%) non-URMs (p = 0.10). No differences in clinical and pathologic stage between the cohorts (p = 0.28) were present. URMs took 22 days longer on average to receive treatment (66.5 days vs. 44.8 days, p = 0.003) in the EP cohort and 18 days longer in OP cohort (58.0 days vs. 40.5 days, p < 0.001) compared with non-URMs. Pancreatic Multidisciplinary Clinic enrollment in EP cohort eliminated the difference in time to treatment between cohorts (48.3 days vs. 37.0 days; p = 0.151).

Results

Underrepresented minorities were more likely to be diagnosed via EP and showed delayed times to treatment compared with non-URM counterparts. Our PMDC alleviated some of these observed disparities. Future studies are required to elucidate the specific factors that resulted in these findings and to identify solutions.
Stage 2 Registered Report: Anomalous perception in a Ganzfeld condition - A meta-analysis of more than 40 years investigation
Authors: Tressoldi Patrizio E. , Storm Lance
Published: May 2024

This meta-analysis is an investigation into anomalous perception (i.e., conscious identification of information without any conventional sensorial means). The technique used for eliciting an effect is the Ganzfeld condition (a form of sensory homogenization that eliminates distracting peripheral noise). The database consists of studies published between January 1974 and December 2020 inclusive. The overall effect size estimated both with a frequentist and a Bayesian random-effect model, were in close agreement yielding an effect size of approximately .08 (.04 -.12). This result passed four publication bias tests and seems not contaminated by questionable research practices. Trend analysis carried out with a cumulative meta-analysis and a meta-regression model with year of publication as a covariate, did not indicate sign of decline of this effect size. The moderators’ analyses show that the selected participants’ effect size was almost three-times that obtained by non-selected participants and that tasks that simulate telepathic communication show a two-fold effect size for tasks requiring the participants to guess a target. The Stage 1 Registered Report can be accessed here: https://doi.org/10.12688/f1000research.24868.3
Acceso a la administración de justicia contencioso-administrativa: descentralización de competencias y creación de juzgados virtuales para litigios electrónicos
Authors: Mejía Guerrero Nicolás Guillermo , Salamanca Giral Nicolás David
Published: May 2024

La estructura institucional de la jurisdicción contencioso-administrativa, al centralizar ciertas competencias en el Consejo de Estado como juez de única instancia, constituye una barrera para garantizar el efectivo acceso a la administración de justicia de la población rural. Particularmente en tres grupos considerados sujetos de especial protección constitucional ocurre este fenómeno: campesinos, indígenas y comunidades. De otra parte, la actualización de la administración de justicia a través de nuevas tecnologías presenta retrasos y dificultades a partir de los ejes sobre los que opera el Plan de Justicia Digital, sobre todo en materia de litigio electrónico y su aplicación en regiones apartadas. En síntesis, a la ruralidad colombiana se le dificulta la garantía de acceso a la administración de justicia a través de barreras físicas —centralización de las competencias— y tecnológicas —deficiencias y lentitud en el plan de justicia digital—.
Like Stars: How Firms Learn at Scientific Conferences
Authors: Baruffaldi Stefano , Poege Felix
Published: May 2024

Scientific conferences are an underexplored channel by which firms can learn from science. We provide empirical evidence that firms learn from scientific conferences in which they participate but also that this is conditional on intense participation. Using data from conference papers in computer science since the 1990s, we show that corporate investments in participation are both frequent and highly skewed, with some firms contributing to a given conference scientifically, some as sponsors, and some doing both. We use direct flights as an instrumental variable for the probability that other scientists participate in the same conference as a firm, altering the knowledge set to which the firm is exposed. We find that a firm’s use of scientists’ knowledge increases when they participate in the same conferences. Greater participation efforts, where the firm seeks the spotlight by both sponsoring the conference and contributing to its scientific discourse, foretell research collaborations and a stronger learning effect. Such learning is disproportionately concentrated among the most prominent firms and scientists rather than benefitting those without alternative interaction channels. Therefore, on average, firms learn from scientists that they encounter at conferences, but the substantial heterogeneity of the effect reflects the influence of reputation mechanisms in social interactions.

This paper was accepted by Ashish Arora, entrepreneurship and innovation.

Funding: S. Baruffaldi acknowledges financial support from the Swiss Science National Foundation (Reference No.: P2ELP1-161847).

Supplemental Material: The online appendix and data files are available at https://doi.org/10.1287/mnsc.2022.01373 .