bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Emergency Department Evaluation With Public Insurance Use and Treatment Delays for ACL Injury
Authors: Zhu Angela S. , Morrissey Patrick , Byrne Rory A. , Albright J. Alex , Lemme Nicholas J. , Cruz Aristides I. , Owens Brett D.
Published: November 2023

Background:

Utilization of an emergency department (ED) visit for anterior cruciate ligament (ACL) injury is associated with high cost and diagnostic unreliability.

Hypothesis:

Patients initially evaluated at an ED for an ACL injury would be more likely to be from a lower income quartile, use public insurance, and experience a delay in treatment.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

Patients in the Rhode Island All Payers Claims Database who underwent ACL reconstruction (ACLR) between 2012 and 2021 were identified using the Current Procedure Terminology (CPT) code 29888. Patients were stratified into 2 cohorts based on CPT codes for ED or in-office services within 1 year of ACLR. A chi-square analysis was used to test for differences between cohorts in patient and surgical characteristics. Multivariable linear and logistic regression were used to determine how ED evaluation affected timing and outcome variables.

Results:

While adjusting for patient and operative characteristics, patients in the ED cohort were more likely to have Medicaid (29% vs 12.5%; P < .001) and be in the lowest income quartile (44.6% vs 32.1%; P < .001). ED visit and Medicaid status were associated with increased time to (1) diagnostic magnetic resonance imaging, adding 7.97 days on average (95% CI, 4.14-11.79 days; P < .001) and 8.40 days (95% CI, 3.44-13.37 days; P = .001), respectively; and (2) surgery, adding 20.30 days (95% CI, 14.10-26.49 days; P < .001) and 12.88 days (95% CI, 5.15-20.60 days; P = .001), respectively. Patients >40 years who were evaluated in the ED were 2.5 times more likely to require subsequent ACLR (odds ratio, 2.50 [95% CI, 1.01-6.21]; P = .049).

Conclusion:

In this study, patients who visited the ED within 1 year before ACLR were more likely to have a lower income, public insurance, increased time to diagnostic imaging, and increased time to surgery, as well as decreased postoperative physical therapy use and increased subsequent ACLR rates in the 40-49 years age-group.
Fetus In Fetu With Myelomeningocele
Authors: Zhim Meriem , Laasri Khadija , Naggar Amine , Rostoum Soufiane , Sfar Kaoutar , Allali Nazik , El Haddad Siham , Chat Latifa
Published: November 2023

Fetus in fetu is an uncommon medical anomaly characterized by the presence of a malformed fetus within the body of a living twin. Although the retroperitoneum is the most typical location, occurrences in the sacrococcygeal and dorsolumbar regions are rare. Ongoing debates center around its embryopathogenesis, debating whether it is a highly specialized teratoma or a result of parasitic twinning in a monozygotic monochorionic diamniotic pregnancy. Notably, distinguishing factors such as vertebral bodies and limbs are pivotal in discerning FIF from teratomas. Diagnostic imaging techniques are integral for preoperative diagnosis, with histopathological examination confirming the condition’s presence
Attitudes and Experiential Factors Associated with Completion of mt-sDNA Test Kit for Colorectal Cancer Screening
Authors: Finney Rutten Lila J. , Zhu Xuan , Treiman Katherine , Madson Gabriel , Southwell Brian , Helmueller Leah , Alam Shama , Gates Carlye , Squiers Linda
Published: November 2023

Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. Despite the availability of multiple screening options, CRC screening is underutilized. We conducted a survey of patients (n = 2973) who were prescribed the multi-target stool DNA (mt-sDNA) screening test (commercialized as Cologuard® and manufactured by Exact Sciences Corporation) to understand attitudes and experiences that influence test completion and likelihood of future test completion. Using exploratory factor analyses, we developed three scales: Perceived Effectiveness, Perceived Ease of Use, and Perceived Comfort.
Awareness and Perceptions of University Nursing Students in Samoa Towards Childhood Hearing Impairment and Hearing Healthcare: A Cross-Sectional Study
Authors: Kaspar Annette , Samuelu-Matthes Ma’atasesa , Driscoll Carlie , Pifeleti Sione
Published: November 2023

Introduction

Pacific Islands have among the highest prevalence of pediatric hearing impairment in the world. Given the limited availability of ear and hearing specialists in the Pacific region, the broader health professional community plays a vital role in the prevention of avoidable pediatric hearing impairment. Nurses emerge as one of the ideal candidates for task-sharing in the administration of ear and hearing care at the public and primary healthcare levels.

Objectives

The aim of this study is to evaluate the awareness and perceptions of university nursing students in Samoa to pediatric hearing impairment and hearing healthcare.

Methods

This study employed a cross-sectional study design. A 10-item questionnaire was administered to university nursing students in Samoa ( N = 100). The statements aimed to evaluate perceptions towards childhood hearing impairment, as well as awareness of causal factors of permanent childhood hearing loss and available hearing healthcare. Participants were required to provide a response based on the five-point Likert scale “Strongly Agree,” “Agree,” “Neutral/Don’t know,” “Disagree,” and “Strongly Disagree.”

Results

Overall, 79% of participants responded “Disagree/Strongly Disagree” to the item “Hearing loss is not that important because it does not kill.” Overall, 52% of respondents were aware of hearing impairment as a public health concern in Samoa. Early identification and intervention services for newborns with hearing impairment are nonexistent in Samoa, and awareness was low for the importance of early detection (62%) and amplification suitability for babies (49%). Overall, awareness was also low for causal factors of permanent sensorineural hearing loss.

Conclusions

A borderline neutral/positive perception was found among our future nursing professionals to engage with pediatric hearing impairment in Samoa. Awareness regarding the causes of permanent childhood hearing impairment, as well as early identification and intervention services, could be integrated in the university curriculum.
Enhancing Equity in a Widening Participation Scheme for School Students
Authors: Kirkham EN , Rozwadowski S , Wijeyaratne M , Ferris L , Bennett J , Coyle M
Published: November 2023

OBJECTIVES

The Royal College of Surgeons (RCS) Diversity Review 2021 found that premedical school students from ethnic minority backgrounds were dissuaded from pursuing a surgical career. Gloucestershire is in the bottom 20% of disadvantaged counties; there is no widening participation (WP) scheme in the county. We implemented a fully inclusive WP scheme in Gloucester, with means of accessing virtual and face-to-face work experience, to enhance the equity of work experience.

METHODS

A three-stage project was conducted. Stage 1; two separate virtual Q and A sessions, to allow students to ask questions about life as a doctor. Stage 2; conversation between student and patient held virtually, to gain insight into working as a doctor to help determine whether medicine is the career for them. Stage 3; face-to-face work experience. Distribution sent to all 58 schools (state and private) in the county, targeted at secondary school children.

RESULTS

One hundred twenty-nine people attended the Q and A; 70 feedback responses received. Of the total, 86% female and 56% of ethnic minority background. 26% did not have an immediate family member that attended university, 10% had care-giving responsibilities. Eighty-one percent rated the session >8/10 for usefulness. Twenty-seven undertook the virtual conversation, feedback from 11; 91% female, 45% of ethnic minority background, and 27% did not have an immediate family member that attended university. All rated the session 10/10 for usefulness. 10 attended the face-to-face experience, 50% from an ethnic minority background.

CONCLUSION

The RCS Report identified barriers to aspiring students from less-privileged backgrounds pursuing a medical career. More needs to be done with WP schemes to promote equity. Targeted distribution of WP schemes to all schools, utilization of a variety of means of offering work experience, and accessibility to any school-aged student were aspects of our WP to improve exposure to the medical profession.
Acute Occlusion of a “Protected” Left Main Coronary Artery Manifesting as an Acute Coronary Syndrome with Heart Failure: How much Protected it is?
Authors: Jariwala Pankaj , Kulkarni Gururaj Pramod , Mishra Krushna Chandra , Jariwala Anusha
Published: November 2023

Despite the progress made in technological advancements, the utilization of stenting for both protected and unprotected left main coronary artery (LMCA) disease remains associated with elevated rates of long-term mortality and significant adverse clinical events, sometimes manifesting as cardiogenic shock. A considerable number of individuals retain the opportunity to receive catheter-based interventional therapy as a viable substitute for re-operative coronary artery bypass grafting (CABG). Despite the changed appearance, patients with acute blockage of the protected LMCA still have major adverse cardiac events (MACE) at a similar rate. Acute occlusion of the unprotected LMCA as an acute coronary syndrome (ACS) is uncommon, but that of the protected LMCA is relatively rare. We present a case of a post-CABG patient who developed ACS as a posterior wall myocardial infarction and acute left ventricular failure due to obstruction of a protected LMCA with substantial stenosis across its distal segment extending to the left circumflex (LCx) artery. The pharmaco-invasive management of the protected LMCA thrombotic occlusion with primary percutaneous coronary intervention resulted in significant patient improvement. These lesions are amenable to complex and high-risk coronary intervention with current technology, and the results have been quite encouraging in terms of long-term survival.
Earthquake response of reinforced concrete frames with infill and active external confinement: Tests and dataset
Authors: Kerby Charles , Monical Jonathan , Pujol Santiago
Published: November 2023

One option to retrofit reinforced concrete (RC) frames is the construction of infill walls. Infill increases lateral strength and stiffness but tends to reduce drift capacity relative to bare frames. Few studies have quantified the reductions in drift demand attributable to infills prior to failure. This report summarizes data from experiments designed to compare drift demands of frames with and without infill. Included data come from two experimental programs completed at Purdue University which focused on the in-plane dynamic response of reduced-scale, non-ductile RC frames to uniaxial simulated earthquake ground motions. 254 dynamic tests were conducted on bare frames, frames with masonry infill walls, and frames with timber infill walls. In 11 of 14 test series, active confinement was applied to columns using external post-tensioned reinforcement. The complete dataset is open-access online on Zenodo, DOI: 10.5281/zenodo.6954967.
The Sonographic Diagnosis and Clinical Management of a Fetal Sacrococcygeal Teratoma: A Case Report
Authors: Akbar Zahraa , Alenezi Hadeel
Published: November 2023

A sacrococcygeal teratoma (SCT) is one of the most common fetal extragonadal germ cell neoplasms and carries high risk of maternal and perinatal complications. An example of a fetal SCT, associated with polyhydramnios, is presented in this case report. An antenatal surveillance sonogram revealed an increase in the size of the teratoma size and the amniotic fluid index. The patient underwent Cesarean delivery and postnatally, the infant’s teratoma was surgically excised. The pathologic examination of the specimen revealed a benign mature teratoma. This case demonstrated the important role that serial sonography had in monitoring this fetal pathology. Prenatal fetal sonographic assessment can play an important role for patients who need counseling and surgical planning.
Being Agile: Transcendent Solutions to Enduring Problems in the Age of COVID-19
Authors: Jaiswal Rachana
Published: November 2023

To stay ahead of market movements and constantly changing stakeholder’s priorities, it is critical for industry moguls and employees to constantly scan for real-time insights into a highly volatile market. A profound shift towards digital transformation during the ongoing pandemic opened a new era of agility in the business sector and acted as an indispensable ingredient for redrafting plans and strategies in a new normal due to that the term “Agile” became a most popular buzzword in the corporate world. The turbulent market impacted every corner of the industry irrespective of size and type of business and compelled them to shift their focus from scale to pace. The pandemic forces us to expedite strategic plans according to the market change to be sustained and not being thrown out by subversive competitors. Therefore, it is recommended to develop tools and models to invigorate the organization from a volatile market through four steps from scratch continuous scanning, orienting the situation faced and finalizing strategy, and working on the action plan. Companies who are aligned with the time and their strategy will lead the market and get competitive advantages over the acute disruption and also be positioned at the top of the K-shaped recovery of the economy. This article is an attempt to provide an insight into agile practices and their managerial implications at the organizational level.
Investigating the prognostic value of digital mobility outcomes in patients with chronic obstructive pulmonary disease: a systematic literature review and meta-analysis
Authors: Buttery Sara C. , Williams Parris J. , Alghamdi Saeed M. , Philip Keir E.J. , Perkins Alexis , Kallis Constantinos , Quint Jennifer K. , Polkey Michael I. , Breuls Sofie , Buekers Joren , Chynkiamis Nikolaos , Delgado-Ortiz Laura , Demeyer Heleen , Frei Anja , Garcia-Aymerich Judith , Gimeno-Santos Elena , Koch Sarah , Megaritis Dimitrios , Polhemus Ashley , Troosters Thierry , Vogiatzis Ioannis , Watz Henrik , Hopkinson Nicholas S.
Published: November 2023

Background:

Reduced mobility is a central feature of COPD. Assessment of mobility outcomes that can be measured digitally (digital mobility outcomes (DMOs)) in daily life such as gait speed and steps per day is increasingly possible using devices such as pedometers and accelerometers, but the predictive value of these measures remains unclear in relation to key outcomes such as hospital admission and survival.

Methods:

We conducted a systematic review, nested within a larger scoping review by the MOBILISE-D consortium, addressing DMOs in a range of chronic conditions. Qualitative and quantitative analysis considering steps per day and gait speed and their association with clinical outcomes in COPD patients was performed.

Results:

21 studies (6076 participants) were included. Nine studies evaluated steps per day and 11 evaluated a measure reflecting gait speed in daily life. Negative associations were demonstrated between mortality risk and steps per day (per 1000 steps) (hazard ratio (HR) 0.81, 95% CI 0.75–0.88, p<0.001), gait speed (<0.80 m·s−1) (HR 3.55, 95% CI 1.72–7.36, p<0.001) and gait speed (per 1.0 m·s−1) (HR 7.55, 95% CI 1.11–51.3, p=0.04). Fewer steps per day (per 1000) and slow gait speed (<0.80 m·s−1) were also associated with increased healthcare utilisation (HR 0.80, 95% CI 0.72–0.88, p<0.001; OR 3.36, 95% CI 1.42–7.94, p=0.01, respectively). Available evidence was of low-moderate quality with few studies eligible for meta-analysis.

Conclusion:

Daily step count and gait speed are negatively associated with mortality risk and other important outcomes in people with COPD and therefore may have value as prognostic indicators in clinical trials, but the quantity and quality of evidence is limited. Larger studies with consistent methodologies are called for.
Relating mutational signature exposures to clinical data in cancers via signeR 2.0
Authors: Drummond Rodrigo D. , Defelicibus Alexandre , Meyenberg Mathilde , Valieris Renan , Dias-Neto Emmanuel , Rosales Rafael A. , da Silva Israel Tojal
Published: November 2023

Background

Cancer is a collection of diseases caused by the deregulation of cell processes, which is triggered by somatic mutations. The search for patterns in somatic mutations, known as mutational signatures, is a growing field of study that has already become a useful tool in oncology. Several algorithms have been proposed to perform one or both the following two tasks: (1) de novo estimation of signatures and their exposures, (2) estimation of the exposures of each one of a set of pre-defined signatures.

Results

Our group developed signeR, a Bayesian approach to both of these tasks. Here we present a new version of the software, signeR 2.0, which extends the possibilities of previous analyses to explore the relation of signature exposures to other data of clinical relevance. signeR 2.0 includes a user-friendly interface developed using the R-Shiny framework and improvements in performance. This version allows the analysis of submitted data or public TCGA data, which is embedded in the package for easy access.

Conclusion

signeR 2.0 is a valuable tool to generate and explore exposure data, both from de novo or fitting analyses and is an open-source R package available through the Bioconductor project at (https://doi.org/10.18129/B9.bioc.signeR).
Exome and genome sequencing to unravel the precise breakpoints of partial trisomy 6q and partial Monosomy 2q
Authors: Zhang Shuang , Cui Qianwei , Yang Shangying , Zhang Fangxia , Li Chunxia , Wang Xiaoguang , Lei Bo , Sheng Xunlun
Published: November 2023

Background

Patients with complex phenotypes and a chromosomal translocation are particularly challenging, since several potentially pathogenic mechanisms need to be investigated.

Case presentation

Here, we combined exome and genome sequencing techniques to identify the precise breakpoints of heterozygous microduplications in the 6q25.3-q27 region and microdeletions in the 2q37.1-q37.3 region in a proband. The 5-year-old girl exhibited a severe form of congenital cranial dysinnervation disorder (CCDD) in addition to skeletal dysmorphism anomalies and severe intellectual disability. This is the second case affecting chromosomes 2q and 6q. The individual’s karyotype showed an unbalanced translocation 46,XX,del(2)t(2;6)(q37.1;q25.3), which was inherited from her unaffected father [46,XY,t(2;6)(q37.1;q25.3)]. We also obtained the precise breakpoints of a de novo heterozygous copy number deletion [del(2)(q37.1q37.3)chr2:g.232963568_24305260del] and a copy number duplication [dup(6)(q25.3q27)chr6:g.158730978_170930050dup]. The parental origin of the observed balanced translocation was not clear because the parents declined genetic testing.

Conclusion

Patients with a 2q37 deletion and 6q25.3 duplication may exhibit severe significant neurological and skeletal dysmorphisms, and the utilization of exome and genome sequencing techniques has the potential to unveil the entire translocation of the CNV and the precise breakpoint.
Surface topography and spectrophotometric assessment of white spot lesions restored with nano-hydroxyapatite-containing universal adhesive resin: an in-vitro study
Authors: Aref Neven S. , Alsdrani Rahaf M.
Published: November 2023

Background

White spot lesion (WSL) is a main shortcoming accompanied by orthodontic treatment. It impairs the esthetic, surface hardness, and surface texture of enamel. So, this study was conducted to analyze the surface characteristics and color change of white spot lesions treated with nano-hydroxyapatite (nHA)-enriched universal adhesive resin.

Materials and methods

Eighty sound human permanent molars crowns were sectioned into two halves, producing 160 specimens. 16 specimens were left untreated, and 144 specimens were artificially-demineralized to generate WSLs. The specimens were classified according to the treatment approach applied as follows: I; Sound enamel, Group II; artificially-created WSLs, Group III; ICON resin-restored WSLs, Group IV; Universal adhesive resin-restored WSLs, Group V; 0.5 wt% nHA-containing universal adhesive resin-restored WSLs, Group VI; 1 wt% nHA-containing universal adhesive resin- restored WSLs, and Group VII; 3 wt% nHA-containing universal adhesive resin-restored WSLs, Group VIII; 5 wt% nHA-containing universal adhesive resin-restored WSLs, Group IX; 7 wt% nHA-containing universal adhesive resin-restored WSLs, and Group X; 10 wt% nHA-containing universal adhesive resin-restored WSLs. Some surface characteristics and color changes were assessed. Data was collected and analyzed statistically using ANOVA and the Tukey test at p < 0.05.

Results

Surface microhardness of WSLs was significantly improved with all investigated ratios of nHA-containing universal adhesive (p < 0.0001), with the highest mean belonging to 10 wt% nHA-containing universal adhesive resin treated WSLs. All ratios of nHA-containing universal adhesive resin significantly reduced the surface roughness of WSLs (p < 0.0001). The investigated ratios of 1, 3, 5, 7, and 10 wt% nHA-containing universal adhesive resin treatment approach could mask the WSLs significantly (p < 0.0001).

Conclusions

Nano-hydroxyapatite-containing universal adhesive is a promising contemporary approach for the management of WSLs, coupled both the remineralizing concept and the minimally invasive resin infiltration.
Convergent evolution of the sensory pits in and within flatworms
Authors: Gąsiorowski Ludwik , Dittmann Isabel Lucia , Brand Jeremias N. , Ruhwedel Torben , Möbius Wiebke , Egger Bernhard , Rink Jochen C.
Published: November 2023

Background

Unlike most free-living platyhelminths, catenulids, the sister group to all remaining flatworms, do not have eyes. Instead, the most prominent sensory structures in their heads are statocysts or sensory pits. The latter, found in the family Stenostomidae, are concave depressions located laterally on the head that represent one of the taxonomically important traits of the family. In the past, the sensory pits of flatworms have been homologized with the cephalic organs of nemerteans, a clade that occupies a sister position to platyhelminths in some recent phylogenies. To test for this homology, we studied morphology and gene expression in the sensory pits of the catenulid Stenostomum brevipharyngium.

Results

We used confocal and electron microscopy to investigate the detailed morphology of the sensory pits, as well as their formation during regeneration and asexual reproduction. The most prevalent cell type within the organ is epidermally-derived neuron-like cells that have cell bodies embedded deeply in the brain lobes and long neurite-like processes extending to the bottom of the pit. Those elongated processes are adorned with extensive microvillar projections that fill up the cavity of the pit, but cilia are not associated with the sensory pit. We also studied the expression patterns of some of the transcription factors expressed in the nemertean cephalic organs during the development of the pits. Only a single gene, pax4/6, is expressed in both the cerebral organs of nemerteans and sensory pits of S. brevipharyngium, challenging the idea of their deep homology.

Conclusions

Since there is no morphological or molecular correspondence between the sensory pits of Stenostomum and the cerebral organs of nemerteans, we reject their homology. Interestingly, the major cell type contributing to the sensory pits of stenostomids shows ultrastructural similarities to the rhabdomeric photoreceptors of other flatworms and expresses ortholog of the gene pax4/6, the pan-bilaterian master regulator of eye development. We suggest that the sensory pits of stenostomids might have evolved from the ancestral rhabdomeric photoreceptors that lost their photosensitivity and evolved secondary function. The mapping of head sensory structures on plathelminth phylogeny indicates that sensory pit-like organs evolved many times independently in flatworms.
Attention-deficit/hyperactivity disorder symptoms and subsequent cardiometabolic disorders in adults: investigating underlying mechanisms using a longitudinal twin study
Authors: Dobrosavljevic Maja , Kuja-Halkola Ralf , Li Lin , Chang Zheng , Larsson Henrik , Du Rietz Ebba
Published: November 2023

Background

Emerging research suggests that attention-deficit/hyperactivity disorder (ADHD) increases the risk for cardiovascular (CVDs) and metabolic disorders (i.e., cardiometabolic disorders) in adulthood. Yet, available studies are scarce and have mainly been focused on individuals receiving clinical ADHD diagnoses. We aimed to investigate the prospective associations of ADHD symptoms in young and mid-adulthood with subsequent cardiometabolic disorders and the underlying mechanisms.

Methods

We studied 10,394 twins from the Swedish Twin Registry (STR), born between 1958 and 1985 without previous medical history of cardiometabolic disorders. They provided self-assessment of ADHD symptoms (score range 0–36) via a validated, DSM-IV-based scale in a web-based questionnaire/telephone interview within the Study of Twin Adults: Genes and Environment (STAGE), in 2005–2006 (aged 19–47 years), and were followed until the end of 2018 (33–59 years) to identify incident clinical diagnoses/medication prescriptions for cardiometabolic disorders acquired from Swedish national registers. We used Cox regression models to investigate the associations between ADHD symptoms score and cardiometabolic outcomes, with and without adjustment for relevant covariates, and a co-twin control design to study familial confounding.

Results

A one-unit increase in the level of ADHD symptoms was associated with a 2% increase in the rate of CVDs (hazard ratio [HR] = 1.02, 95% confidence interval 1.01–1.04) and a 3% increase in the rate of metabolic disorders (HR = 1.03, 1.02–1.05), after adjusting for birth year and sex. The associations were no longer significant after adjusting for educational attainment, lifestyle factors, and comorbid psychiatric disorders. The associations remained significant after adjusting for familial factors shared by dizygotic twin pairs but became nonsignificant after adjusting for factors shared by monozygotic twin pairs. However, the strength of the associations attenuated significantly in monozygotic twins compared to dizygotic twins for CVDs only, suggesting genetic confounding.

Conclusions

ADHD symptom score is associated with a higher risk for cardiometabolic disorders, which may be explained by lower educational attainment, adverse lifestyle factors, and psychiatric comorbidities. Moreover, the associations appear to be partly confounded by shared genetic factors, especially for CVDs. Further research is needed to investigate the identified associations at the level of individual cardiometabolic disorders and to follow-up participants until a more advanced older age.
P2X7 receptor activation leads to NLRP3-independent IL-1β release by human macrophages
Authors: Bockstiegel Judith , Engelhardt Jonas , Weindl Günther
Published: November 2023

Background

The purinergic receptor P2X7 plays a crucial role in infection, inflammation, and cell death. It is thought that P2X7 receptor stimulation triggers processing and release of the pro-inflammatory cytokine interleukin (IL)-1β by activation of the NLRP3 inflammasome; however, the underlying mechanisms remain poorly understood.

Methods

Modulation of IL-1β secretion was studied in THP-1 macrophages. Adenosine 5’-triphosphate (ATP), BzATP, nigericin and pharmacological inhibitors of P2X receptors, inflammatory caspases and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome were used to characterize signaling.

Results

In primed macrophages, IL-1β release was increased after P2X7 receptor activation by ATP and 2,3-O-(4-benzoylbenzoyl)-ATP (BzATP). Pharmacological inhibition or genetic knockout of NLRP3 does not completely inhibit IL-1β release in TLR2/1-primed macrophages. Increase in extracellular K+ as well as inhibition of caspase-1 or serine proteases maintained IL-1β release in macrophages stimulated with P2X7 receptor agonists at 50%.

Conclusions

Our findings suggest a previously unrecognized mechanism of P2X7 receptor mediated IL-1β release and highlight the existence of an NLRP3-independent pathway in human macrophages.
Improving the therapeutic efficacy of oncolytic viruses for cancer: targeting macrophages
Authors: Shen Zhen , Liu Xiyu , Fan Guixiang , Na Jintong , Liu Qiaoqiao , Lin Faquan , Zhang Zhikun , Zhong Liping
Published: November 2023

Oncolytic viruses (OVs) for cancer treatment are in a rapid stage of development, and the direct tumor lysis and activation of a comprehensive host immune response are irreplaceable advantages of cancer immunotherapy. However, excessive antiviral immune responses also restrict the spread of OVs in vivo and the infection of tumor cells. Macrophages are functionally diverse innate immune cells that phagocytose tumor cells and present antigens to activate the immune response, while also limiting the delivery of OVs to tumors. Studies have shown that the functional propensity of macrophages between OVs and tumor cells affects the overall therapeutic effect of oncolytic virotherapy. How to effectively avoid the restrictive effect of macrophages on OVs and reshape the function of tumor-associated macrophages in oncolytic virotherapy is an important challenge we are now facing. Here, we review and summarize the complex dual role of macrophages in oncolytic virotherapy, highlighting how the functional characteristics of macrophage plasticity can be utilized to cooperate with OVs to enhance anti-tumor effects, as well as highlighting the importance of designing and optimizing delivery modalities for OVs in the future.
Talniflumate abrogates mucin immune suppressive barrier improving efficacy of gemcitabine and nab-paclitaxel treatment in pancreatic cancer
Authors: Agostini Antonio , Guerriero Ilaria , Piro Geny , Quero Giuseppe , Roberto Luca , Esposito Annachiara , Caggiano Alessia , Priori Lorenzo , Scaglione Giulia , De Sanctis Francesco , Sistigu Antonella , Musella Martina , Larghi Alberto , Rizzatti Gianenrico , Lucchetti Donatella , Alfieri Sergio , Sgambato Alessandro , Bria Emilio , Bizzozero Laura , Arena Sabrina , Ugel Stefano , Corbo Vincenzo , Tortora Giampaolo , Carbone Carmine
Published: November 2023

Background

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. This is due to its aggressive course, late diagnosis and its intrinsic drugs resistance. The complexity of the tumor, in terms of cell components and heterogeneity, has led to the approval of few therapies with limited efficacy. The study of the early stages of carcinogenesis provides the opportunity for the identification of actionable pathways that underpin therapeutic resistance.

Methods

We analyzed 43 Intraductal papillary mucinous neoplasms (IPMN) (12 Low-grade and 31 High-grade) by Spatial Transcriptomics. Mouse and human pancreatic cancer organoids and T cells interaction platforms were established to test the role of mucins expression on T cells activity. Syngeneic mouse model of PDAC was used to explore the impact of mucins downregulation on standard therapy efficacy.

Results

Spatial transcriptomics showed that mucin O-glycosylation pathway is increased in the progression from low-grade to high-grade IPMN. We identified GCNT3, a master regulator of mucins expression, as an actionable target of this pathway by talniflumate. We showed that talniflumate impaired mucins expression increasing T cell activation and recognition using both mouse and human organoid interaction platforms. In vivo experiments showed that talniflumate was able to increase the efficacy of the chemotherapy by boosting immune infiltration.

Conclusions

Finally, we demonstrated that combination of talniflumate, an anti-inflammatory drug, with chemotherapy effectively improves anti-tumor effect in PDAC.
Optimizing percutaneous vertebroplasty: extra-facet puncture for osteoporotic vertebral compression fractures
Authors: Zheng Huo-Liang , Li Bo , Jiang Qin-Yu , Jiang Lei-Sheng , Zheng Xin-Feng , Jiang Sheng-Dan
Published: November 2023

Purpose

To assess the safety and efficacy of the extra-facet puncture technique applied in unilateral percutaneous vertebroplasty (PVP) for treating osteoporotic vertebral compression fractures.

Methods

Demographics (age, gender, body mass index and underlying diseases) were recorded for analyzing. Visual analog scale (VAS) and Oswestry Disability Index (ODI) scores as well as their corresponding minimal clinically important difference (MCID) were used to evaluate clinical outcomes. The segmental kyphotic angle, the vertebral compression ratio and bone cement distribution pattern were evaluated by the plain radiographs. The facet joint violation (FJV) was defined by the postoperative computed tomography scan. Binary logistic regression analysis was performed to investigate relationships between multiple risk factors and residual back pain.

Results

VAS and ODI scores in both traditional puncture group and extra-facet puncture group were significantly decreased after PVP surgery (p < 0.05). However, no significant difference was observed between the two groups according to VAS and ODI scores. The proportion of patients achieving MCID of VAS and ODI scores was higher in extra-facet puncture group as compared to traditional puncture group within a month (p < 0.05). Finally, multivariate logistic regression analysis showed that FJV (odds ratio 16.38, p < 0.001) and unilateral bone cement distribution (OR 5.576, p = 0.020) were significant predictors of residual back pain after PVP surgery.

Conclusions

Extra-facet puncture percutaneous vertebroplasty can decrease the risk of FJV and it also has the advantage of more satisfied bone cement distribution.
CSPG4 CAR-redirected Cytokine Induced Killer lymphocytes (CIK) as effective cellular immunotherapy for HLA class I defective melanoma
Authors: Giraudo Lidia , Cattaneo Giulia , Gammaitoni Loretta , Iaia Ilenia , Donini Chiara , Massa Annamaria , Centomo Maria Laura , Basiricò Marco , Vigna Elisa , Pisacane Alberto , Picciotto Franco , Berrino Enrico , Marchiò Caterina , Merlini Alessandra , Paruzzo Luca , Poletto Stefano , Caravelli Daniela , Biolato Andrea Michela , Bortolot Valentina , Landoni Elisa , Ventin Marco , Ferrone Cristina R. , Aglietta Massimo , Dotti Gianpietro , Leuci Valeria , Carnevale-Schianca Fabrizio , Sangiolo Dario
Published: November 2023

Background

Even acknowledging the game-changing results achieved in the treatment of metastatic melanoma with the use of immune checkpoint inhibitors (ICI), a large proportion of patients (40–60%) still fail to respond or relapse due to the development of resistance. Alterations in the expression of Human Leukocyte Antigen class I (HLA-I) molecules are considered to play a major role in clinical resistance to ICI. Cellular immunotherapy with HLA-independent CAR-redirected lymphocytes is a promising alternative in this challenging setting and dedicated translational models are needed.

Methods

In this study, we propose an HLA-independent therapeutic strategy with Cytokine Induced Killer lymphocytes (CIK) genetically engineered with a Chimeric Antigen Receptor (CAR) targeting the tumor antigen CSPG4 as effector mechanism. We investigated the preclinical antitumor activity of CSPG4-CAR.CIK in vitro and in a xenograft murine model focusing on patient-derived melanoma cell lines (Mel) with defective expression of HLA-I molecules.

Results

We successfully generated CSPG4-CAR.CIK from patients with metastatic melanoma and reported their intense activity in vitro against a panel of CSPG4-expressing patient-derived Mel. The melanoma killing activity was intense, even at very low effector to target ratios, and not influenced by the expression level (high, low, defective) of HLA-I molecules on target cells. Furthermore, CAR.CIK conditioned medium was capable of upregulating the expression of HLA-I molecules on melanoma cells. A comparable immunomodulatory effect was replicated by treatment of Mel cells with exogenous IFN-γ and IFN-α. The antimelanoma activity of CSPG4-CAR.CIK was successfully confirmed in vivo, obtaining a significant tumor growth inhibition of an HLA-defective Mel xenograft in immunodeficient mice.

Conclusions

In this study we reported the intense preclinical activity of CSPG4-CAR.CIK against melanoma, including those with low or defective HLA-I expression. Our findings support CSPG4 as a valuable CAR target in melanoma and provide translational rationale for clinical studies exploring CAR-CIK cellular immunotherapies within the challenging setting of patients not responsive or relapsing to immune checkpoint inhibitors.
Effects of SARS-CoV-2 infection on embryological outcomes in assisted reproductive technology during the Omicron epidemic
Authors: Mao Yuling , Yao Yachao , Du Hongzi , Wang Zheng , Zhou Xueliang , Zeng Ming , Wang Chunyan , Liu Hanyan , Luo Yang , Hong Honghai , Liu Jianqiao , Li Lei
Published: November 2023

Background

The influence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on assisted reproductive technology (ART) has received increasing attention. It has been reported that the SARS-CoV-2 RiboNucleic Acid (RNA) cannot be detected in follicular fluid and granulosa cells. However, the detection rate of SARS-CoV-2 RNA in immature oocytes and blastocysts has still unknown. Moreover, the effect of SARS-CoV-2 infection on embryological outcomes in ART during the Omicron epidemic is limited.

Methods

A prospective study was performed to explore the detection rate of viral RNA in biological specimens from patients who tested positive for SARS-CoV-2 RNA and the effects of SARS-CoV-2 infection on embryological outcomes. A total of 211 patients underwent transvaginal oocyte retrieval at the Third Affiliated Hospital of Guangzhou Medical University between December 13, 2022 and December 30, 2022. Prior to transvaginal oocyte retrieval, 61 individuals tested positive for SARS-CoV-2 RNA within 24 h. Follicular fluid was preserved during oocyte retrieval. Granular cells were collected after degranulation (Intracytoplasmic sperm injection only). Immature oocytes were collected at the end of the ICSI. Unavailable blastocysts were collected on day 6 (D6). The TIANLONG SARS-CoV-2 RT-PCR-Kit was used to detect SARS-CoV-2 RNA in all samples. The COVID-19 and Non COVID-19 groups were contrasted in the following areas: fertilization rate, 2PN rate, Day 3 (D3) available embryos rate, D3 good-quality embryos rate, blastocyst formation rate, good-quality blastocyst formation rate.

Results

All samples were negative except for an immature oocytes sample that was positive for SARS-CoV-2 viral RNA with a detection rate of 6.67%. Whether in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), the rate of fertilization, 2PN, D3 available embryos, D3 good-quality embryos, blastocyst formation, good-quality blastocyst formation was not significantly negative different between the COVID-19 and the Non COVID-19 groups. Our findings were validated by an overview of the embryological outcome from the cycles before SARS- Cov-2 infection from the same patient.

Conclusions

Except for immature oocytes, none of the follicular fluid, granulosa cells, or blastocysts samples contained viral RNA. In addition, SARS-CoV-2 infection had no detrimental effects on the embryological outcomes of ART.
Erythropoietic protoporphyria: case reports for clinical and therapeutic hints
Authors: Tumminelli Cristina , Burlo Francesca , Pastore Serena , Severini Giovanni Maria , Berti Irene , Marchini Stefano , Zanon Davide , De Martino Eleonora , Tommasini Alberto
Published: November 2023

Background

Erythropoietic protoporphyria is a rare disorder which represents an important health problem in children, causing painful photosensitivity. Little is known on the correlation between genetic profile and clinical manifestations. The standard of care for Erythropoietic protoporphyria is based on avoiding sun and using sun protections, but recent literature has suggested that cimetidine may have a role in improving sun sensitivity. Herein we report our case series describing the successful use of cimetidine and analyzing potential phenotype-genotype correlations.

Case presentation

This case series describes five patients presented to our Rheumatology Service complaining sun sensitivity. Blood exams and genetic analysis were consistent with the diagnosis of erythropoietic protoporphyria. Four of 5 patients received cimetidine in addition to standard therapies and the effect of treatment was evaluated by Erythropoietic Protoporphyria - Quality of Life questionnaire.

Conclusions

Erythropoietic protoporphyria usually manifests in early childhood after a short sun exposure. Skin manifestations are the main reason for investigations, although sometimes they can be more subtle, leading to a significant diagnostic delay. Skin diseases in children can have profound effects on their family and social relationships. A treatment with cimetidine appears to be an excellent therapeutic option in children with Erythropoietic protoporphyria.
Effect of wearing peripheral focus-out glasses on emmetropization in Chinese children aged 6–8 years: study protocol for a 2-year randomized controlled intervention trial
Authors: Shen Li , He Wennan , Yang Weiming , Yan Weili , Yang Chenhao
Published: November 2023

Background

Myopia is one of the most common eye diseases causing visual impairment and blindness, and the high prevalence in adolescents remains a major public health concern. Based on clinical studies using optical defocus to regulate ocular growth and refractive changes through visual feedback, we hypothesize that early wearing of peripheral myopic defocusing spectacles in children with high risk of myopia may slow the process of emmetropization and even prevent the onset of myopia by inducing more peripheral myopic defocus. The aim of this study is to investigate whether the wearing of peripheral focus-out glasses can be effective in delaying emmetropization in non-myopic children aged 6–8 years.

Methods

The study is a 2-year randomized controlled trial. A total of 160 subjects will be randomized into the experimental group or the control group. The experimental group will be fitted with direct emmetropia with focus-out glasses (DEFOG) to guide the emmetropization process. The control group will not receive any treatment and will serve as a blank control group. The primary aim is to determine whether non-myopic children wearing DEFOG lenses are superior to those who do not receive any intervention on the progression of cycloplegic objective refraction over 2 years.

Discussion

This is the first randomized controlled trial aiming at myopic prevention by non-invasive intervention in non-myopic children. This study aims to initially investigate whether wearing peripheral focus-out glasses can effectively delay the process of emmetropization in children aged 6–8 years with high risk of myopia, which might give potential clues for further exploration on early prevention of myopia.

Trial registration

ClinicalTrials.gov NCT05689567. Registered on 10 January 2023.
Impact of carbonization conditions and adsorbate nature on the performance of activated carbon in water treatment
Authors: Karume Ibrahim , Bbumba Simon , Tewolde Simon , Mukasa Is’harq Z. T. , Ntale Muhammad
Published: November 2023

The physical and chemical structure of activated carbon (AC) varies with the carbonization temperature, activation process and time. The texture and toughness of the starting raw material also determine the morphology of AC produced. The Brunauer-Emmet-Teller surface area (SBET) is small for AC produced at low temperatures but increases from 500 to 700 °C, and generally drops in activated carbons synthesized > 700 °C. Mild chemical activators and low activator concentrations tend to generate AC with high SBET compared to strong and concentrated oxidizing chemicals, acids and bases. Activated carbon from soft starting materials such as cereals and mushrooms have larger SBET approximately twice that of tough materials such as stem berks, shells and bones. The residual functional groups observed in AC vary widely with the starting material and tend to reduce under extreme carbonization temperatures and the use of highly concentrated chemical activators. Further, the adsorption capacity of AC shows dependency on the size of the adsorbate where large organic molecules such as methylene blue are highly adsorbed compared to relatively small adsorbates such as phenol and metal ions. Adsorption also varies with adsorbate concentration, temperature and other matrix parameters.
Understanding factors associated with the trajectory of subjective cognitive complaints in groups with similar objective cognitive trajectories
Authors: Cacciamani Federica , Bercu Ariane , Bouteloup Vincent , Grasset Leslie , Planche Vincent , Chêne Geneviève , Dufouil Carole ,   for the MEMENTO Cohort Study Group
Published: November 2023

Background

Cognitive complaints are often regarded as an early sign of Alzheimer’s disease (AD) but may also occur in several other conditions and contexts. This study examines the correlates of cognitive complaint trajectories over a 5-year period in individuals who shared similar objective cognitive trajectories.

Methods

We analyzed a subsample (n = 1748) of the MEMENTO cohort, consisting of individuals with subjective cognitive decline or mild cognitive impairment at baseline. Participants were stratified based on their latent MMSE trajectory over a 5-year period: “high and increasing,” “subtle decline,” and “steep decline.” Within each of the three strata, we used a latent-class longitudinal approach to identify distinct trajectories of cognitive complaints. We then used multiple logistic regressions to examine the association between these complaint trajectories and several factors, including AD biomarkers (blood pTau/Aβ42 ratio, cortical thickness, APOE genotype), anxiety, depression, social relationships, a comorbidity-polypharmacy score, and demographic characteristics.

Results

Among participants with high and increasing MMSE scores, greater baseline comorbidity-polypharmacy scores (odds ratio (OR) = 1.30, adjusted p = 0.03) were associated with higher odds of moderate and increasing cognitive complaints (as opposed to mild and decreasing complaints). Baseline depression and social relationships also showed significant associations with the complaint pattern but did not survive correction for multiple comparisons. Among participants with subtle decline in MMSE scores, greater baseline depression (OR = 1.76, adjusted p = 0.02) was associated with higher odds of moderate and increasing cognitive complaints (versus mild and decreasing). Similarly, baseline comorbidity-polypharmacy scores and pTau/Aβ42 ratio exhibited significant associations, but they did not survive correction. Among participants with a steep decline in MMSE scores, greater baseline comorbidity-polypharmacy scores increased the odds of moderate complaints (versus mild, OR = 1.38, unadjusted p = 0.03, adjusted p = 0.32), but this effect did not survive correction for multiple comparisons.

Conclusions

Despite similar objective cognitive trajectory, there is heterogeneity in the subjective perception of these cognitive changes. This perception was explained by both AD-related and, more robustly, non-AD-related factors. These findings deepen our understanding of the multifaceted nature of subjective cognitive complaints in individuals at risk for dementia and underscore the importance of considering a range of factors when interpreting cognitive complaints.