bluuebunny/crossref_metadata_2025 huggingface dataset:
WELLENS SYNDROME: TIMELY RECOGNITION AND SUCCESSFUL REVASCULARIZATION
Authors: Liberatore I , Terrinoni F , Commisso C , Patrizi R , Cittadini E , Palermo M , Granatelli A
Published: May 2024

Wellens syndrome is a condition characterized by clinical and instrumental signs suggestive of a critical proximal left anterior descending (LAD) coronary artery stenosis and requires early revascularization. Diagnostic criteria include T–wave changes in ECG during asymptomatic periods in patients with a history of chest pain, absence of significant cardiac enzyme movement, no ST–segment elevation, preserved R–wave, and no pathological Q waves. Early recognition of this syndrome is crucial, due to its 10–15% prevalence, allowing proper management and myocardial function recovery, avoiding potentially catastrophic outcomes. A 64–year–old male, with hypertension, undiagnosed diabetes, and family history of CAD, presented to our ER with sudden, brief chest pain radiating to the left upper limb. Similar episodes had occurred in the past week. The patient denied previous cardiovascular events and home therapy. ECG conducted by the attending cardiologist, during free chest pain period, showed biphasic T–wave in V1–V3 (a). Admission ECG resembled the ambulatory one. Lab results: Hb 14.7 g/dl, Troponin I 0.059 ng/ml (cut–off 0.034). Echocardiogram indicated distal septum akinesia. Urgent coronary angiography was performed, detecting subocclusive stenosis in the proximal–mid LAD. Successful revascularization was achieved by PTCA and implantation of 1 DES. (b) Subsequently, the patient was admitted to the Cardiac Intensive Care Unit for multiparametric monitoring. The ECG showed deeply negative T waves from V1 to V6. (c) No complications during hospitalization. Discharge ECG showed repolarization anomalies improvement. Echocardiography revealed preserved systolic function, without global or segmental anomalies in wall motion. Wellens syndrome is a manifestation of acute coronary syndrome that precedes an anterior wall MI. This condition can be identified by its characteristic T–wave patterns on ECG. Patients with this syndrome have severe LAD occlusion and require early coronary intervention. In chest pain episodes, the ECG appears normal, and troponin levels often remain within the normal range, which can potentially provide false reassurance. Wellens syndrome is a cardiac emergency requiring immediate attention; it is crucial for the physician to promptly identify the typical ECG signs of Wellens Syndrome, facilitating early coronary revascularization to prevent adverse patient outcomes.
TRANSIENT GLOBAL AMNESIA AND CONCOMITANT TAKOTSUBO CARDIOMYOPATHY: A CASE SERIES
Authors: Borsi L , Di Spigno F , Biagi A , Rusticali G , Turchio P , Tedeschi A , Aschieri D
Published: May 2024

Transient global amnesia (TGA) is a clinical syndrome characterized by the sudden onset of anterograde amnesia, accompanied by repetitive questioning lasting up to 24 hours with whole restoration and without compromise of other neurologic function. Case reports suggest that cardiac dysfunctions may also occur in patients TGA although until now, no study has systematically assessed this phenomenon. Several pathophysiologic mechanisms have been proposed, with particular emphasis on the role of the central and autonomic nervous systems and an increased sympathetic hyperactivity, likewise to Takotsubo Syndrome (TTS). A case series of two cases (one man and one woman) of TGA as a precocious display of concomitant Takotsubo cardiomyopathy was described.
ISCHEMIC MITRAL REGURGITATION: MV-TEER AS AN ALTERNATIVE TO SURGERY IN HEMODINAMICALLY UNSTABLE PATIENT
Authors: Leuzzi F , Esposito L , Cancro F , Attisano T , Pierri A , Maione A , Di Muro M , Ravera A , Citro R , Vigorito F , Galasso G , Baldi C
Published: May 2024

Background

Severe ischemic mitral regurgitation is a complication that develops in approximately 7% of patients with STEMI. It can be caused by the rupture of a papillary muscle or, more frequently, by unfavorable regional remodeling of the left ventricle, and is burdened by a mortality up to 50%. The optimal treatment is controversial, because of the high surgical risk of these patients; at the same time, conservative management is not able to manage the most compromised cases and is associated with an unfavorable prognosis. In these patients, percutaneous mitral valve repair with edge-to-edge technique (MV-TEER) can be considered a reasonable alternative.

Clinical History

A 62-year-old woman was admitted to the emergency room with a diagnosis of lateral STEMI; she was immediately transferred to the catheterization laboratory where a primary PCI on the circumflex branch, in a left-dominant coronary circulation, was performed. Despite a normal epicardial coronary flow, probably due to a no-reflow phenomenon, echocardiography revealed severe left ventricular dysfunction secondary to an inferior and posterolateral wall akinesia, which at the same time was responsible for a newly severe secondary mitral regurgitation (SMR). In the following day the patient developed the signs of cardiogenic shock associated with pulmonary edema unresponsive to conventional therapy. Given the patient’s worsening symptoms, the inefficacy of the medical therapy, the severe SMR and the high operative risk, the clinical case was evaluated in the heart team and the final decision was to proceed to MV-TEER with the MitraClip system. 7 days after the MI, the patient underwent successful TEER with the implantation of 2 G4 NTW® clips in A2/P2 position. The patient was discharged 11 days after TEER. At 6,12 and 18-months follow-up, the patient showed a mild residual SMR and reported a significant improvement of symptoms (NYHA Class I). The patient has never been hospitalized for decompensated heart failure and returned to a good quality of life.

Discussion

Acute ischemic SMR complicated by hemodynamic instability is associated with a high risk of in-hospital mortality. The critical condition of these patients often represents a contraindication to cardiac surgery. In this specific setting, TEER is a valuable therapeutic option, as it might effectively reduce SMR, improving the hemodynamic condition and ultimately resulting in a better short- and mid-term survival compared to surgery.
DEVELOPMENT OF A HUB–SPOKE NETWORK FOR TRANSCATHTER AORTIC VALVE IMPLANTATION: THE INTERVENTIONAL CARDIOLOGY UNIT OF IRCCS SAN RAFFAELE HOSPITAL (OSR HUB–SPOKE)
Authors: Federico F , Zanda G , Ferri L , Martino G , Harris R , Ancona M , Vella C , Russo F , Bellini B , Ghizzoni G , Gentile D , Dallavalle F , Gentilini C , Bonfanti P , Corrado G , Chieffo A , Montorfano M
Published: May 2024

Background

The growing prevalence of aortic stenosis determined in recent years an increase in candidates for percutaneous aortic valve replacement (TAVI), bringing out a difficult access to this procedure. In order to reduce waiting lists and to guarantee the training of the Interventional Cardiologists of Centers not equipped with on–site cardiac surgery, we implemented a TAVI protocol with one Hub center, the Interventional Cardiology Unit of IRCCS San Raffaele Scientific Institute, Milan, and two participating Spoke Centers: the ASST–Franciacorta Chiari Center and Valduce Hospital, Como.The aim of this study is to report in hospital outcomes of patients treated using this model of Hub–Spoke Network.

Methods

Patients included in this model were selected in the Spoke center where baseline clinical evaluation with echocardiography and CT scan were performed (inclusion and exclusion criteria attached). The cases were then discussed with a multidisciplinary team on–line and the procedure planned (access, valve type size). Once the procedure was scheduled, the patients underwent a single day transport to the Hub Center where they underwent TAVI and a same day return to the Spoke Center. A bailout hospitalization in the Hub Center was available in case of major complication. All Spoke Centers patients who underwent TAVI procedures in our Center according to our protocol were included in this analysis. The primary study objective was in hospital major adverse cardiac events (all cause or cardiovascular mortality, stroke, myocardial infarction); secondary study objectives were technical success, prolonged recovery in Hub Center and major vascular complications.

Results

Since 2019, a total of 69 patients underwent TAVI with the Hub and Spoke model. Mean age was 83 years ± 6 and mean ejection fraction was 59% ± 7%. Two patients (2.9%) had a prolonged hospitalization in the Hub center for a major vascular complication and an intra–procedural cardiac arrest, successfully resuscitated. Technical success was reached in 97.1% of patients. One patient experimented an ischemic stroke after the return in the spoke center: in hospital MACE was than 1.4%.

Conclusion

Considering the growing prevalence of aortic stenosis, The Hub Spoke Model for TAVI guarantees reduction in waiting lists, "access to care" for patients referred to Spoke centers, involvement and improvement of skills of their Interventional Cardiologists, keeping a high level of safety and efficacy.
COMPLEX LEFT ATRIAL APPENDAGE CLOSURE USING 3D PRINTING SYSTEM IN A PATIENT WITH RECURRENT EMBOLISM AND PREVIOUS MITRAL PROSTHETIC VALVE IMPLANTATION
Authors: Tarantini R , Pignalosa L , Marconi S , Sanzo A , Vicini Scajola L , Quilico F , Magrini G , Savastano S , Baldi E , Petracci B , Vicentini A , Rordorf R
Published: May 2024

Background

To prevent stroke in patients with atrial fibrillation (AF), oral anticoagulation (OAC) is often prescribed especially for those with high risk (CHADS2–VASC score ≥ 2), however some patients present contraindications to OAC or they have persistent thrombosis. Left atrial appendage (LAA) closure (LAAc) has emerged as a safe and effective alternative to oral anticoagulation (OAC) for stroke prevention in patients with atrial fibrillation (AF).

Case Description

A 61–year–old woman was referred to our cardiology department for left atrial appendage (LAA) closure (LAAc). She had history of previous mitral valve surgery and replacement with mechanical prothesis (On–X 25/33 mm) and permanent atrial fibrillation (AF) with CHADS2–VASC score 4 and HAS–BLED score 2. The patient presented after a third episode of cardioembolic stroke and transesophageal echocardiography (TEE) revealed a thrombus within the LAA despite anticoagulation treatment. Due to multiple episodes of embolic stroke despite adequate oral anticoagulation, the patient was candidate for LAAc. In preparation for the procedure, TEE and computed tomography (CT) scan were performed to evaluate the anatomy, the size and the potential interference of the prosteshis ring with the LAA. Spontaneous echocontrast was present, the morphology was cauliflower with the ostium close to the mitral prosthesis ring. The anomalous anatomy of the patient increased the technical complexity of the intervention: thus, the procedure’s simulation on a 3D printed model resulted of great help in the choice of the most suitable device. The model was printed in deformable material mimicking the atrial wall mechanical behaviour. After written informed consent, the procedure was performed using a standard transvenous approach. Transseptal puncture was performed postero–inferiorly under TEE guidance and Watchman FLX 35 mm was successfully implanted without residual leak. No complications occurred during the procedure. At 1–month follow–up visit, imaging demonstrated complete LAA occlusion and correct placement of the device with an adequate compression and no residual leak.

Conclusion

This is a clinical case that describes complex LAAc in a patient with mechanical prosthetic mitral valve. Simulating the patient’s anatomy with a 3D–printed model can be useful in complex LAAc procedures to guide prosthesis selection and device sizing reducing procedure time and the risk of failure.
MITRACLIP TREATMENT FOR CARDIOGENIC SHOCK DUE TO ACUTE MITRAL REGURGITATION IN A PATIENT WITH POSTINFARCTION PAPILLARY MUSCLE RUPTURE
Authors: Capodaglio I , Tofoni P , Lofiego C , Vagnarelli F , Patani F , Brugiatelli L , Maurizi K , Pietrucci F , Perna G , Marco M , Piva T , Dello Russo A , Di Eusanio M
Published: May 2024

A 85–year–old woman presented to ED with worsening dyspnea for 24 hours; no other related symptom. Her medical history included hypertension, dyslipidemia, type 2 DM and surgical coronary revascularization 13 years before for multiple critical coronary artery disease (LIMA to LAD and sequential SVG to PDA and OM branch). The ECG promptly revealed a subacute infero–lateral STEMI. Transthoracic echocardiography (TTE) showed inferior and postero–lateral wall akinesia with severely reduced left ventricle ejection fraction (LVEF), mildly reduced right ventricle systolic function and severe mitral regurgitation (MR) due to posterior papillary muscle (PM) rupture (Fig.1). Clinical scenario was complicated by pulmonary edema and cardiogenic shock treated with diuretics and sodium nitroprusside infusion, non–invasive ventilation and IABP insertion. Urgent coronary angiography revealed a thrombotic occlusion of the venous graft for OM branch. Surgical correction was excluded due to hemodynamic instability. Graft occlusion was treated with manual thromboaspiration, balloon dilatations and abciximab infusion. After an initial stabilization, transesophageal echocardiography (TEE) was performed confirming severe MR resulting from rupture of one head of a bifid posterior PM (red arrows, Fig.1) and prolapse of the anterior leaflet combined with restrictive systolic movement of the posterior leaflet due to wall motion abnormalities. 3 days later a transcatheter mitral valve edge–to–edge repair (MTEER) was performed using a MitraClip device (1 XTR clip and 1 NTR clip, Fig.2). TEE with 3D and TrueVue vision confirmed the correct placement of clips (Fig.3), a mild–to–moderate residual MR, absence of significant transmitral gradient and a mildly reduced LVEF. No clinical events were reported during recovery; patient was discharged after 2 weeks.

Conclusion

MTEER is an established therapy for reducing degenerative and functional MR. Little data is available on its use in the setting of PM rupture. This rare complication of AMI carries a mortality rate of 80% during the first week without surgical correction but more than half of patients are excluded because of prohibitive operative risk. TEER may be an alternative for these patients. In this case report we described the utility of MTEER in the setting of cardiogenic shock secondary to acute ischemic MR with papillary muscle partial rupture. This procedure can be useful with acceptable safety and procedural success.
VALVE–IN–VALVE TRANSCATHETER AORTIC VALVE REPLACEMENT: EL DORADO OR EXIT–STRATEGY?
Authors: Costantino M , Stolfi L , D‘Addeo G , Cortese F , Tucci M , Morea C , Veglia G , Magnante A
Published: May 2024

Introduction

The Valve–in–Valve Transcatheter Aortic Valve Replacement (ViV–TAVR) procedure is a valid alternative treatment to surgery.

Aim

This study evaluates, from a clinical and echocardiographic point of view, the immediate and one–year postprocedural outcome of the ViV–TAVR in case of dysfunction of a biological prosthesis at the aortic site.

Materials and Methods

Between 2021 and 2022, 17 consecutive patients with stenosis (64.71%) or aortic valve insufficiency (35.29%) underwent ViV–TAVR procedure and we evaluated them echocardiographically for 12 months.

Results

The implanted valves (10 of 20 mm, 5 of 23 mm, 1 of 26 mm and one of 29 mm in diameter) were Sapien XT type in 4 patients and Sapien 3 in 13 cases (of which 3 Ultra). We reported the Kaplan–Meier curve referring to one–year mortality in the presence/absence of coronary heart disease. Degeneration of bioprostheses in patients aged ≤ 70 years at the time of implantation occurred on average in 10.89±2.98 years, in patients aged >70 years in 7.88±2.23 years after implantation intervention. For all patients we calculated the mean change in end–diastolic volume (EDV) between the value at baseline, immediately after ViV–TAVR and at one–year follow–up. On patients who had bioprosthesis dysfunction with stenosis, we calculated the change in the mean transvalvular gradient (Gm) and Doppler Velocity Index (DVi) at baseline, immediately after ViV–TAVR and at follow–up.

Conclusions

The analyzed echocardiographic parameters were improved after ViV–TAVR both in the immediate post–procedural and in the follow–up period.
Margaret Macdonald, Philosopher of Language
Authors: Spinney Oliver Thomas
Published: May 2024

I chart the philosophical development of neglected figure Margaret Macdonald and situate that development in the context of mid-century analytic philosophy more broadly. I examine Macdonald’s changing attitude towards verificationism, and show that these changing views led her, in 1950 and beyond, to a very thorough appreciation of language use as capable of being employed in the execution of distinctive kinds of performative act. I compare Macdonald’s views with the far better known work of J. L. Austin, and I emphasise the extent to which she has, despite her insightful contributions, been omitted from the history of philosophy.
Theranostics in Neuroendocrine Tumors
Authors: Mallak Nadine , O'Brien Sophia R. , Pryma Daniel A. , Mittra Erik
Published: May 2024

Neuroendocrine tumors (NETs) are rare tumors that develop from cells of the neuroendocrine system and can originate in multiple organs and tissues such as the bowels, pancreas, adrenal glands, ganglia, thyroid, and lungs. This review will focus on gastroenteropancreatic NETs (more commonly called NETs) characterized by frequent somatostatin receptor (SSTR) overexpression and pheochromocytomas/paragangliomas (PPGLs), which typically overexpress norepinephrine transporter. Advancements in SSTR-targeted imaging and treatment have revolutionized the management of patients with NETs. This comprehensive review delves into the current practice, discussing the use of the various Food and Drug Administration–approved SSTR-agonist positron emission tomography tracers and the predictive imaging biomarkers, and elaborating on 177Lu-DOTATATE peptide receptor radionuclide therapy including the evolving areas of posttherapy imaging practices and peptide receptor radionuclide therapy retreatment. SSTR-targeted imaging and therapy can also be used in patients with PPGL; however, this patient population has demonstrated the best outcomes from norepinephrine transporter-targeted therapy with 131I-metaiodobenzylguanidine. Metaiodobenzylguanidine theranostics for PPGL will be discussed, noting that in 2024 it became commercially unavailable in the United States. Therefore, the use and reported success of SSTR theranostics for PPGL will also be explored.
Transforming into a Learning Health System: A Quality Improvement Initiative
Authors: Chiem Jennifer L. , Hansen Elizabeth E. , Fernandez Nicolas , Merguerian Paul A. , Parikh Sanjay R. , Reece Kayla , Low Daniel K. , Martin Lynn D.
Published: May 2024

Background:

The Institute of Medicine introduced the Learning Healthcare System concept in 2006. The system emphasizes quality, safety, and value to improve patient outcomes. The Bellevue Clinic and Surgical Center is an ambulatory surgical center that embraces continuous quality improvement to provide exceptional patient-centered care to the pediatric surgical population.

Methods:

We used statistical process control charts to study the hospital’s electronic health record data. Over the past 7 years, we have focused on the following areas: efficiency (surgical block time use), effectiveness (providing adequate analgesia after transitioning to an opioid-sparing protocol), efficacy (creating a pediatric enhanced recovery program), equity (evaluating for racial disparities in surgical readmission rates), and finally, environmental safety (tracking and reducing our facility’s greenhouse gas emissions from inhaled anesthetics).

Results:

We have seen improvement in urology surgery efficiency, resulting in a 37% increase in monthly surgical volume, continued adaptation to our opioid-sparing protocol to further reduce postanesthesia care unit opioid administration for tonsillectomy and adenoidectomy cases, successful implementation of an enhanced recovery program, continued work to ensure equitable healthcare for our patients, and more than 85% reduction in our facility’s greenhouse gas emissions from inhaled anesthetics.

Conclusions:

The Bellevue Clinic and Surgical Center facility is a living example of a learning health system, which has evolved over the years through continued patient-centered QI work. Our areas of emphasis, including efficiency, effectiveness, efficacy, equity, and environmental safety, will continue to impact the community we serve positively.
Osteomyelitis and Pathologic Fracture of Mandible in Undiagnosed Osteopetrosis
Authors: Sahoo N.K , Jain Titiksha , Pawar Gaurav , Maheshwari Isha , Balagopal Athira
Published: May 2024

Osteopetrosis (OP) is a heterogeneous group of rare, heredity bone disorders with variable clinical features involving the bones of the body. OP is characterized by increased bone density, which is caused by aberrant osteoclast-mediated bone resorption. This syndromic disorder comes with a series of problems and, unless recognized and treated early, can lead to a multitude of further grave complications. We report a rare case of a female patient who reported chronic unhealed extraoral draining sinus present over the left submandibular region with pathologic fracture of the left mandibular angle, which, if, was diagnosed early with the identification of the osteopetrosis syndrome, could have been managed more conservatively.
A Novel Regulation on the Developmental Checkpoint Protein Sda that Controls Sporulation and Biofilm Formation inBacillus subtilis
Authors: He Yinghao , Qin Yuxuan , Greenwich Jennifer , Balaban Samantha , Darcera Migue Van Louis , Gozzi Kevin , Chai Yunrong
Published: May 2024

Biofilm formation byBacillus subtilisis triggered by an unusually simple environmental sensing mechanism. Certain serine codons, the four TCN codons (N for A, T, C, or G), in the gene for the biofilm repressor SinR caused lowered SinR translation and subsequent biofilm induction during transition from exponential to stationary growth. Global ribosome profiling showed that ribosomes pause when translating the four UCN (U for T on the mRNA) serine codons on mRNA, but not the two AGC/AGU serine codons. We proposed a serine codon hierarchy (AGC/AGT vs TCN) in that genes enriched in the TCN serine codons may experience reduced translation efficiency when serine is limited. In this study, we designed an algorithm to score all protein-coding genes inB. subtilisNCIB3610 based on the serine codon hierarchy. We generated a short list of 50 genes that could be subject to regulation by this novel mechanism. We further investigated one such gene from the list,sda, which encodes a developmental checkpoint protein regulating both sporulation and biofilm formation. We showed that synonymously switching the TCN serine codons to AGC insdaled to delayed biofilm formation and sporulation. This engineered strain also outgrew strains with other synonymously substitutedsdaalleles (TCN) in competition assays for biofilm formation and sporulation. Lastly, we showed that the AGC serine codon substitutions insdaelevated the Sda protein levels. This serine codon hierarchy-based novel signaling mechanism could be exploited by bacteria in adapting to stationary phase and regulating important biological processes.

Importance

Genome-wide ribosome profiling inBacillus subtilisshows that under serine limitation, ribosomes pause on the four TCN (N for A, C, G, and T), but not AGC/AGT serine codons, during translation at a global scale. This serine codon hierarchy (AGC/T vs TCN) differentially influences translation efficiency of genes enriched in certain serine codons. In this study, we designed an algorism to score all 4000+ genes in theB. subtilisgenome and generated a list of 50 genes that could be subject to this novel serine codon hierarchy-mediated regulation. We further investigated one such gene,sda, encoding a developmental check point protein. We show thatsdaand cell developments controlled by Sda are also regulated by this novel mechanism.
Correcting model misspecification in relationship estimates
Authors: Jewett Ethan M. ,   the 23andMe Research Team
Published: May 2024

1.

Abstract

The datasets of large genotyping biobanks and direct-to-consumer genetic testing companies contain many related individuals. Until now, it has been widely accepted that the most distant relationships that can be detected are around fifteen degrees (approximately 8thcousins) and that practical relationship estimates have a ceiling around ten degrees (approximately 5thcousins). However, we show that these assumptions are incorrect and that they are due to a misapplication of relationship estimators. In particular, relationship estimators are applied almost exclusively to putative relatives who have been identified because they share detectable tracts of DNA identically by descent (IBD). However, no existing relationship estimator conditions on the event that two individuals share at least one detectable segment of IBD anywhere in the genome. As a result, the relationship estimates obtained using existing estimators are dramatically biased for distant relationships, inferring all sufficiently distant relationships to be around ten degrees regardless of the depth of the true relationship. Existing relationship estimators are derived under a model that assumes that each pair of related individuals shares a single common ancestor (or mating pair of ancestors). This model breaks down for relationships beyond 10 generations in the past because individuals share many thousands of cryptic common ancestors due to pedigree collapse. We first derive a corrected likelihood that conditions on the event that at least one segment is observed between a pair of putative relatives and we demonstrate that the corrected likelihood largely eliminates the bias in estimates of pairwise relationships and provides a more accurate characterization of the uncertainty in these estimates. We then reformulate the relationship inference problem to account for the fact that individuals share many common ancestors, not just one. We demonstrate that the most distant relationship that can be inferred using IBD may be 200 degrees or more, rather than ten, extending the time-to-common ancestor from approximately 300 years in the past to approximately 3,000 years in the past or more. This dramatic increase in the range of relationship estimators makes it possible to infer relationships whose common ancestors lived before historical events such as European settlement of the Americas, the Transatlantic Slave Trade, and the rise and fall of the Roman Empire.
Methyltransferase DNMT3B promotes colorectal cancer cell proliferation by inhibiting PLCG2
Authors: Ji Yong , Wang Yang , Zou Jiacheng , Liu Guanghao , Xia Mingyu , Ren Jun , Wang Daorong
Published: May 2024

Background

Aberrant DNA methylation patterns in the promoter region of PLCG2 have been associated with dysregulated signaling pathways and cellular functions. Its role in colorectal cancer cells is still unknown.

Methods

qRT-PCR was used to examine DNMT3B expression in colorectal cancer. Western blot and immunohistochemistry were used to analyze DNMT3B and PLCG2 protein levels in colorectal tissues and cell lines. The cell counting kit-8 and colony experiments were used to identify the proliferation of colorectal cancer cells. Methylation-specific PCR (MSP) and bisulfite-sequencing PCR (BSP) was used to measure DNA methylation levels.

Results

DNMT3B is overexpressed in colorectal cell in TCGA datasets and Kaplan-Meier plots. DNMT3B is significantly overexpressed in tumor tissues compared to adjacent non-tumor tissues. Western blotting results demonstrated high expression of DNMT3B in tumor tissues.

Compared to normal colonic epithelial cells, colorectal cancer cell lines exhibited elevated levels of PLCG2 methylation. oePLCG2 effectively prevented the in vivo xenograft tumor growth of colorectal cancer.

Conclusions

PLCG2 is identified as a key downstream regulatory protein of DNMT3B in colorectal cancer. DNMT3B Inhibits PLCG2 transcription through methylation of the PLCG2 promoter region. DNMT3B controls colorectal cancer cell proliferation through the PLCG2, which is useful for creating therapeutic approaches that target PLCG2 expression for the treatment of colorectal cancer.
Macrophage Infiltration and ITGB2 Expression in ESCC: A Novel Correlation
Authors: Huang Tao , Wei Longqian , Liu Jun , Zhou Huafu
Published: May 2024

Esophageal squamous cell carcinoma (ESCC), one of the most prevalent and deadliest malignancies today, still presents significant limitations in the application and efficacy of immunotherapy. In this study, we comprehensively utilized high-throughput sequencing, gene chips, single-cell sequencing, and various bioinformatics analysis methods to uncover, for the first time, a positive correlation between the infiltration level of macrophages and the expression of ITGB2 in ESCC.ITGB2 is overexpressed in ESCC and holds immense potential as a prognostic marker for ESCC. As ESCC progresses, the expression of ITGB2 increases within infiltrating macrophages. We also proposed for the first time that the expression of ITGB2 in macrophages continues to increase as macrophages shift towards a pro-tumor phenotype. We found that evaluating the immune therapy response in ESCC patients using ITGB2 is feasible, and higher expression of ITGB2 correlates with increased feasibility of targeting macrophages. Additionally, we identified three miRNAs associated with aberrant expression of ITGB2, providing references for further exploration of upstream molecules of ITGB2.
Implemented Interventions in Preventing Surgical Site Infection in Pediatric Appendicitis Patients: A Scoping Review
Authors: Hebballi Nutan B. , Sutyak Krysta , Broussard Maryam , Doughty Caroline , Garcia Elisa , Lally Kevin P. , Blakely Martin L. , Tsao KuoJen
Published: May 2024

Objective

Surgical site infections (SSIs), especially deep/organ-space SSIs, are common and serious complications following appendectomy. This review aimed to explore the interventions that have been implemented to reduce the risk of SSIs in pediatric appendicitis patients.

Methods

A literature search was performed using PubMed, Cochrane, and Embase databases of studies in English published between January 01, 1973, and April 30, 2023. Studies on pediatric patients (≤ 18 years) with appendicitis that described any interventions aimed at reducing SSIs and reported SSIs as an outcome were included.

Results

A total of 56 studies were included in the final scoping review. The interventions included antibiotic stewardship, clinical practice guidelines/pathways, different surgical approaches, timing of appendectomy, irrigation or lavage, use of peritoneal drains, timing of wound closure and management, parenteral nutrition, pain management, and outpatient management.

Conclusion

A wide variety of interventions have been studied in pediatric appendicitis patients to reduce the SSI rates. Very few publications have studied low-cost, widely available intraoperative interventions to reduce deep/organ-space SSIs.
Substrate stiffness regulates collective colony expansion of the social bacteriumMyxococcus xanthus
Authors: Faiza Nuzhat , Welch Roy , Patteson Alison
Published: May 2024

Many cellular functions depend on the physical properties of the cell’s environment. Many bacteria have different types of surface appendages to enable adhesion and motion on a variety of surfaces.Myxococcus xanthusis a social soil bacterium with two distinctly regulated modes of surface motility, termed the social motility mode driven by type iv pili and the adventurous motility mode based on focal adhesion complexes. How bacteria sense different surfaces and subsequently coordinate their collective motion remains largely unclear. Using polyacrylamide hydrogels of tunable stiffness, we found that wild-typeM. xanthusspreads faster on stiffer substrates. Here, we show using motility mutants that disrupt adventurous motility suppresses this substrate-stiffness response, suggesting focal-adhesion-based adventurous motility is substrate-stiffness dependent. We also show that modifying surface adhesion by the addition of adhesive ligands, chitosan, increases the amount ofM. xanthusflairs, a characteristic feature of adventurous motility. Taken together, we hypothesize a central role ofM. xanthusadventurous motility as a driving mechanism for surface and surface stiffness sensing.
Unveiling the Molecular Mechanisms of the Type-IX Secretion System’s Response Regulator: Structural and Functional Insights
Authors: Saran Anshu , Kim Hey-Min , Manning Ireland , Hancock Mark A. , Schmitz Claus , Madej Mariusz , Potempa Jan , Sola Maria , Trempe Jean-François , Zhu Yongtao , Davey Mary Ellen , Zeytuni Natalie
Published: May 2024

The Type-IX secretion system (T9SS) is a nanomachinery utilized by bacterial pathogens to facilitate infection. The system is regulated by a signaling cascade serving as its activation switch. A pivotal member in this cascade, the response regulator protein PorX, represents a promising drug target to prevent the secretion of virulence factors. Here, we provide a comprehensive characterization of PorX bothin vitroandin vivo. First, our structural studies revealed PorX harbours a unique enzymatic effector domain, which, surprisingly, shares structural similarities with the alkaline phosphatase superfamily, involved in nucleotide and lipid signaling pathways. Importantly, such pathways have not been associated with the T9SS until now. Enzymatic characterization of PorX’s effector domain revealed a zinc-dependent phosphodiesterase activity, with active site dimensions suitable to accommodate a large substrate. Unlike typical response regulators that dimerize via their receiver domain upon phosphorylation, we found that zinc can also induce conformational changes and promote PorX’s dimerization via an unexpected interface. These findings suggest that PorX can serve as a cellular zinc sensor, broadening our understanding of its regulatory mechanisms. Despite the strict conservation of PorX in T9SS-utilizing bacteria, we demonstrate that PorX is essential for virulence factors secretion inPorphyromonas gingivalisand affects metabolic enzymes secretion in the non-pathogenicFlavobacterium johnsoniae, but not for the secretion of gliding adhesins. Overall, this study advances our structural and functional understanding of PorX, highlighting its potential as a druggable target for intervention strategies aimed at disrupting the T9SS and mitigating virulence in pathogenic species.
Efficiency enhancement techniques in finite element analysis: navigating complexity for agile design exploration
Authors: Haider Aun
Published: May 2024

Purpose

This paper aims to comprehensively explore techniques for reducing solution time in finite element analysis (FEA), addressing the critical need for expediting computations to facilitate agile design exploration within project timelines.

Design/methodology/approach

Drawing from a wide array of literature sources, this paper synthesizes and analyzes various methodologies used to enhance the efficiency of FEA. Techniques are scrutinized in terms of their applicability, effectiveness and potential limitations.

Findings

The review signifies application of linear assumptions across multiple facets of analysis and delves into matrix order reduction strategies, geometry simplification, symmetry exploitation, submodeling and mesh attribute control. It reveals how these techniques can effectively reduce computational burdens while maintaining acceptable levels of accuracy.

Research limitations/implications

While this review provides a comprehensive overview of existing efficiency enhancement techniques in FEA, it acknowledges inherent limitations of any synthesis-based study. Future research should focus on refining these methodologies.

Practical implications

The insights provided in this paper offer practical guidance for structural engineers and researchers seeking to optimize FEA workflows. By implementing these techniques, practitioners can expedite solution times and enhance their ability to explore design alternatives efficiently ultimately leading to cost savings and more robust structures.

Originality/value

This review contributes to the existing literature by offering a comprehensive synthesis of efficiency enhancement techniques in FEA. By highlighting the originality and value of each discussed methodology, this paper provides a roadmap for future research and practical implementation in the field of structural engineering.
Multidisciplinary analysis and structural optimization for the aeroelastic sizing of a UAV wing using open-source code integration
Authors: Benaouali Abdelkader , Boutemedjet Abdelwahid
Published: May 2024

Purpose

This paper aims to propose a structural sizing approach of an unmanned aerial vehicle (UAV) wing that takes into account the aeroelasticity effects through a fluid–structure interaction analysis.

Design/methodology/approach

The sizing approach proposed in this study is an iterative process, each iteration of which consists of two sub-loops, a multidisciplinary analysis (MDA) loop followed by a structural optimization loop. The MDA loop seeks the aeroelastic equilibrium between aerodynamic forces and structural displacements using a fixed-point iteration scheme. Once the equilibrium is reached, the converged pressure loads are used for the structural optimization, which aims to find the structural thicknesses that minimize the wing weight under failure criteria. The two sub-loops are run sequentially in an iterative process until the mass is converged. The analysis models are implemented in open-source software, namely, PANUKL for aerodynamics and MYSTRAN for structures, while the whole process is automated with Python and integrated in the open-source optimization framework OpenMDAO.

Findings

The approach was applied to the design of the Predator MQ-1 wing. The results of the MDAs show the convergence of the wing deformations to the flight shape after few iterations. At the end of the aeroelastic sizing loop, the result is a structurally sized wing with minimal weight considering the aeroelasticity effects.

Originality/value

The approach proposed takes into account the wing aero-structural coupling effects while sizing its structure instead of a fixed load distribution. In addition, the approach is fully based on open-source codes, which are freely available for public use and can be fully reproducible.
Responsible innovation and sustainable competitive advantage: is big data the missing link?
Authors: Riaz Adil , Ali Fouzia Hadi
Published: May 2024

Purpose

This study aims to examine the influence of organizational flexibility (OF) and shared vision (SV) on sustainable competitive advantage (SCA) with the mediation role of responsible innovation (RI) in the manufacturing industry of a developing country. Furthermore, big data analytics capability (BDAC) serves as a moderator between RI and SCA.

Design/methodology/approach

The study's hypotheses are investigated using the structural equation modeling (SEM) method. Through simple random sampling, information was gathered from 247 owners/managers of manufacturing SMEs.

Findings

The results elucidate that OF and SV significantly determine RI and SCA. Moreover, RI significantly mediates between SV, OF and SCA. Besides, RI significantly determines SCA. BDAC significantly leads to SCA. Finally, BDAC significantly moderates between RI and SCA.

Research limitations/implications

RI is crucial for manufacturing small and medium-sized enterprises (SMEs) to gain SCA and BDAC is important to address the changing demands of consumers for environment-friendly products. This study gives the public an overview of the different degrees to which SMEs are embracing RI and BDAC; with more environment-friendly initiatives, the natural environment will become more sustainable. Environmental sustainability will benefit each individual living in society.

Originality/value

This study adds value to the existing literature by focusing on predictors that affect SCA. Using dynamic capability theory, this initial study examines the influence of SV and OF on SCA and RI as mediators. Furthermore, BDAC is used as a moderating variable between RI and SCA. Managers, students and researchers can benefit from this study.
Topological optimization in 3D-magnetostatics: development of adjoint methods using the equations of magnetic moments
Authors: Michel Sophie , Messine Frederic , Poirier Jean-René
Published: May 2024

Purpose

The purpose of this paper is mainly to develop the adjoint method within the method of magnetic moment (MMM) and thus, to provide an efficient new way to solve topology optimization problems in magnetostatic to design 3D-magnetic circuits.

Design/methodology/approach

First, the MMM is recalled and the optimization design problem is reformulated as a partial derivative equation-constrained optimization problem where the constraint is the Maxwell equation in magnetostatic. From the Karush–Khun–Tucker optimality conditions, a new problem is derived which depends on a Lagrangian parameter. This problem is called the adjoint problem and the Lagrangian parameter is called the adjoint parameter. Thus, solving the direct and the adjoint problems, the values of the objective function as well as its gradient can be efficiently obtained. To obtain a topology optimization code, a semi isotropic material with penalization (SIMP) relaxed-penalization approach associated with an optimization based on gradient descent steps has been developed and used.

Findings

In this paper, the authors provide theoretical results which make it possible to compute the gradient via the continuous adjoint of the MMMs. A code was developed and it was validated by comparing it with a finite difference method. Thus, a topology optimization code associating this adjoint based gradient computations and SIMP penalization technique was developed and its efficiency was shown by solving a 3D design problem in magnetostatic.

Research limitations/implications

This research is limited to the design of systems in magnetostatic using the linearity of the materials. The simple examples, the authors provided, are just done to validate our theoretical results and some extensions of our topology optimization code have to be done to solve more interesting design cases.

Originality/value

The problem of design is a 3D magnetic circuit. The 2D optimization problems are well known and several methods of resolution have been introduced, but rare are the problems using the adjoint method in 3D. Moreover, the association with the MMMs has never been treated yet. The authors show in this paper that this association could provide gains in CPU time.
Key barriers and mitigation strategies towards sustainable prefabricated construction – a case of developing economies
Authors: Jayawardana Janappriya , Sandanayake Malindu , Jayasinghe Supun , Kulatunga Asela , Zhang Guomin
Published: May 2024

Purpose

The present study aims to identify significant barriers to adopting prefabricated construction (PFC) in developing economies using a study in Sri Lanka and develop an integrated strategy framework to mitigate and overcome the obstacles.

Design/methodology/approach

The research process included a comprehensive literature review, a pilot study, a questionnaire survey for data collection, statistical analysis and a qualitative content analysis.

Findings

Ranking method revealed that all 23 barriers were significant. Top significant barriers include challenges in prefabricated component transportation, high capital investment costs and lack of awareness of the benefits of PFC among owners/developers. Factor analysis clustered six barrier categories (BCs) that fit the barrier factors, explaining 71.22% of the cumulative variance. Fuzzy synthetic evaluation revealed that all BCs significantly influence PFC adoption in Sri Lanka. Finally, the proposed mitigation strategies were mapped with barriers to complete the integrated framework.

Practical implications

The study outcomes are relevant to construction industry stakeholders of Sri Lanka, who are keen to enhance construction efficiencies. The implications can also benefit construction industry stakeholders and policymakers to formulate policies and regulations and identify mitigation solutions.

Originality/value

The study provides deeper insights into the challenges to adopting prefabrication in South Asian countries such as Sri Lanka. Furthermore, the integrated framework is a novel contribution that can be used to derive actions to mitigate barriers in developing economies.
Citizens’ role and digitalisation in the participatory budgeting to create public value: the case of Rome
Authors: Santolamazza Valentina , Mattei Giorgia , Grandis Fabio Giulio
Published: May 2024

Purpose

In recent years, the public sector has faced the challenge of digitalisation. This has significantly impacted the relationships between citizens and public organisations and, thus, it widely affects participatory processes, such as participatory budgeting (PB); in fact, digital tools (DTs) have emerged as a solution, increasing citizen engagement whilst improving efficiency, reducing costs and saving time. This contribution analyses PB in Rome, which is also implemented with DTs, seeking to understand how DTs impact citizens’ role in creating public value.

Design/methodology/approach

The study is based on a qualitative approach, precisely by analysing a descriptive and exploratory single case study of PB’s first adoption in Rome in 2019. The information is obtained from multiple sources and examined through document analysis.

Findings

In the Roman context, DTs in PB primarily facilitated cost-effective information sharing, offering citizens basic participation. Unfortunately, the potential for more interactive DTs was overlooked, failing to enhance citizen engagement in critical phases like deliberation, evaluation or monitoring. Therefore, the tools did not fully support citizens becoming co-creators of public value instead of just users in governance.

Originality/value

The novelty of this study lies in exploring the difference between the use of DTs that assist citizens/users in improving service quality and those that support citizens in creating a public and shared value. It ventures further to assess various tiers of participation, meditating on the digital elements that stimulate active engagement and value creation instead of simply expanding the participant pool or process efficiency.