bluuebunny/crossref_metadata_2025 huggingface dataset:
Non‐interventional, prospective, observational study on spasticity‐associated symptom control with nabiximols as add‐on therapy in patients with multiple sclerosis spasticity in Austria
Authors: Guger Michael , Hatschenberger Robert , Leutmezer Fritz
Published: March 2023

Background and purpose

Randomized controlled trials and observational studies of nabiximols oromucosal spray in patients with multiple sclerosis (MS) spasticity have shown improvement in a range of associated symptoms (pain, spasms, fatigue, bladder dysfunction, and sleep disturbances). This study evaluated the effectiveness and tolerability of add‐on nabiximols in the routine management of patients with MS spasticity in Austria, with a focus on spasticity‐associated symptoms.

Methods

This was an open, prospective, multicenter, observational, non‐interventional study of patients with MS spasticity receiving add‐on treatment with nabiximols oromucosal spray. Main endpoints were patient‐reported changes from baseline in the frequency (counts) or severity (mean Numerical Rating Scale [NRS] scores) of spasticity‐associated symptoms, and patient‐reported changes from baseline in impairment of daily activities due to spasticity, after 1 and 3 months of nabiximols treatment. No analyses were conducted for statistical significance.

Results

There were 55 patients in the effectiveness population, and 62 in the safety population. Patients reported clinically relevant reductions from baseline to month 3 in the average number of spasms/day (−68.2%) and number of urinary incontinence episodes (−69.3%) in the week prior to the clinic visit, and reductions in mean 0−10 NRS scores for sleep impairment (−47.2%), fatigue (−26.4%), pain (40.4%), and spasticity severity (39.0%). There was no change from baseline in daily activity impairment due to spasticity. The majority of patients were at least partly satisfied with add‐on nabiximols for spasticity‐associated symptoms. There were 31 adverse events (27 treatment related) reported in 19 patients, with no new safety signals.

Conclusions

Add‐on nabiximols improved the severity of MS spasticity and a range of spasticity‐associated symptoms during real‐world use in Austria. Nabiximols is an option for patients with MS spasticity who fail first‐line oral antispasticity treatment.
Forensic assessment instruments: Their reliability and applicability to criminal forensic issues
Authors: Rogers Richard , Tazi Kamar Y. , Drogin Eric Y.
Published: March 2023

Forensic evaluations have advanced considerably with the development of specialized measures validated on forensic and correctional samples. Prior to this progress, such evaluations relied heavily on extrapolations from general psychological tests to crucial, legally relevant questions. Since then, decades of empirical work have produced forensic assessment instruments (FAIs) addressing psycholegal standards in addition to forensically relevant instruments (FRIs) examining issues central to forensic practice (e.g., malingering) but not the standards themselves. This article provides a critical examination of the development, validation, and modern applications of six published FAIs that each address one of three broad criminal forensic issues (i.e., insanity, competency to stand trial, and Miranda abilities and waivers). Evaluations of the measures' reliability and validity particularly in forensic samples are highlighted. To complement FAIs, FRIs related to response styles are briefly explored. As a primary goal, forensic practitioners are provided with the knowledge and background about FAIs to enhance their criminal forensic practices.
A prospective study of psychological distress among patients with advanced cancer and their caregivers
Authors: Teo Irene , Ng Sean , Bundoc Filipinas Gines , Malhotra Chetna , Ozdemir Semra , Steel Jennifer L. , Finkelstein Eric A. ,   COMPASS Group
Published: March 2023

Background

Cancer can impact the psychological well‐being of both patients and their informal caregivers. We investigated the joint trajectories of psychological distress among Singaporean advanced cancer patients–caregiver dyads. We also examined predictors of trajectory group membership.

Methods

This study utilised data from 299 patients with advanced solid cancer and their caregivers over 33 months (12 times points). Group‐based trajectory modelling was used to examine the joint trajectories of patient anxiety, patient depression, caregiver anxiety and caregiver depression scores using the Hospital Anxiety and Depression Scale.

Results

Four joint trajectory groups were found: (1) Patient–caregiver low distress (27%), (2) patient–caregiver increasing distress (28.5%), (3) patient low‐ caregiver borderline distress (25%), (4) patient‐caregiver high distress (19.5%). Dyads where the patient is below 50 years of age were more likely to be in Group 4. Dyads where caregiver–patient emotional closeness was low were more likely to be in Groups 2 or 4 where dyads reported increasing/high distress. Dyads that reported financial inadequacy were more likely to be in Groups 2, 3 and 4, while dyads with caregivers who were employed were more likely to be in group 3.

Conclusions

A substantial proportion of patients and caregivers reported anxiety and/or depression that lasted or increased throughout the study duration. We found significant heterogeneity in how dyads experienced psychological distress, suggesting that efforts should consider dyadic differences when providing psychological support. Particular focus should be placed on identifying dyads that are at risk and who require additional support.
Prior irinotecan exposure does not preclude benefit to liposomal irinotecan in patients with metastatic pancreatic ductal adenocarcinoma
Authors: Yu Kenneth H. , Cockrum Paul , Surinach Andy , Lamarre Neil , Wang Shu , O'Reilly Eileen M.
Published: March 2023

Background

Subgroup analyses of the NAPOLI‐1 study identified that among patients who were irinotecan naïve prior to entering the clinical trial, a survival benefit was observed between the study arm and control arm. This treatment benefit was not observed among those previously exposed to irinotecan. This study sought to understand the impact of prior exposure to irinotecan on clinical outcomes among patients treated with liposomal irinotecan in the real‐world setting.

Methods

This retrospective observational study utilized a nationwide electronic health record (EHR)‐derived deidentified database. Data for adult patients with mPDAC treated with liposomal irinotecan‐based regimens between January 2016 and October 2020 were analyzed. Patient characteristics, overall survival (OS), and progression‐free survival (PFS) were assessed. Cox proportional hazard methods were used to calculate hazard ratios (HRs). HRs were adjusted for demographics and relevant clinical covariates.

Results

Six hundred and seventy‐five patients with mPDAC treated with a liposomal irinotecan‐based regimen were included. The unadjusted OS HR was 1.3 (95% CI: 1.1–1.6, p < 0.001) and unadjusted PFS was HR 1.4 (95% CI: 1.2–1.7, p < 0.001). After adjustment for baseline characteristics, the adjusted OS HR was 1.0 (95% CI: 0.8–1.3, p = 0.8836) and the adjusted PFS HR was 1.1 (95% CI: 0.8–1.4, p = 0.5626).

Conclusions

Prior irinotecan was not found to be a significant predictor of patient outcomes in those later treated with liposomal irinotecan. Thus, the results may inform the rationale for utilizing liposomal irinotecan combination therapy following prior irinotecan exposure in mPDAC, in particular where the prior irinotecan exposure was more distant in time.
Investigating the efficiency of lung multi‐disciplinary team meetings—A mixed methods study of eight lung multi‐disciplinary teams
Authors: Zasada Magdalena , Harris Jenny , Groothuizen Johanna , Aroyewun Eunice , Mendis Jeewaka , Taylor Cath , Hewish Madeleine
Published: March 2023

Background

Multidisciplinary team meetings (MDTMs), where treatment recommendations are discussed and agreed, are fundamental to effective cancer care. The increasing volume and complexity of caseloads has led to the need to transform MDTM pathways to improve efficiency and allow sufficient time for discussion of complex cases. Understanding of current functioning and inefficiencies is required to inform such transformation.

Methods

A mixed‐methods observational study of all lung cancer MDTMs in one UK cancer network over 12 weeks (n = 8 MDTs, 96 MDT meetings). Data were collected on meeting attendance and on each discussed case using a validated MDT tool. Semi‐structured interviews were conducted with a range of MDT members and cancer service managers to gain understanding of perceived influences on the efficiency of MDTMs.

Results

In total, 1671 case discussions were observed. Models of MDT working, including referral and diagnostic pathway management, varied within the network. Attendance was quorate in only 21% of the observed MDTMs, most often lacking palliative care specialists. Over a third (37%) of observed cases were repeat discussions pre‐diagnosis. Treatment recommendations were agreed in 48% of case discussions but deferred for a quarter (24%) of discussed cases, most commonly due to awaiting results. Information about patients' fitness for treatment and/or performance status score was available for 60% of cases discussed overall (30%–75% by MDT). Interviews (n = 56) identified addressing clinical and administrative workforce shortages, less reliance on the MDTM for pre‐diagnostic decision‐making and better availability of key clinical information about patients discussed in the MDTM as factors critical to improved MDT function.

Conclusions

Inefficiencies were prevalent in all MDTMs; improvements would require an individualised approach due to the variation in ways of working. Local, regional and national support is needed for lung MDTs to develop their diagnostic workforce and facilities, and clinical and administrative resource.
Competing risk model for prognostic comparison between clear cell type and common type hepatocellular carcinoma: A population‐based propensity score matching study
Authors: Zhong Xiao , Hu Xingwang , Fan Xue‐Gong
Published: March 2023

Background

Clear cell type hepatocellular carcinoma (HCC) is an uncommon neoplasm with an ambivalent prognosis compared to common type HCC.

Methods

First, patients with clear cell or common type HCC were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database, and their demographic and clinical characteristics were identified. Next, overall survival (OS), disease‐specific survival (DSS), and subgroup analysis of the two types of HCC were performed. Next, we utilized a competing risk model to focus on cancer‐caused death. Finally, propensity score matching (PSM) was employed to reduce the confounding factors based on the histopathological type, and sensitivity analysis was conducted.

Results

A total of 205 cases of clear cell type HCC and 29,954 cases of common type HCC were enrolled in our study. Patients with clear cell type HCC were older and predominantly female than those with common type HCC. OS and DSS were not significantly different between the two groups, and histopathological type was not a prognostic factor of HCC, as verified by the competing risk model. Patient characteristics adjusted by PSM and sensitivity analysis confirmed this conclusion. In subgroup analysis, patients with clear cell type HCC at grade III ~ IV and with lymph nodes metastasis had a better prognosis compared to common type HCC.

Conclusions

This study revealed that the prognosis of clear cell type HCC is similar to common type HCC. Tumor differentiation grade and status of lymph node metastasis affect the prognosis of HCC.
Depleting the 19S proteasome regulatory PSMD1 subunit as a cancer therapy strategy
Authors: Adler Julia , Oren Roni , Shaul Yosef
Published: March 2023

Background

Proteasome inhibitors are in use in treating certain types of cancers. These drugs inhibit the catalytic activity of the 20S proteasome, shared by all the different proteasome complexes. Inhibitors of the 26S‐associated deubiquitinating activity explicitly inhibit the 26S proteasomal degradation of ubiquitinylated substrates. We have previously reported an alternative strategy that is based on reducing the 26S/20S ratio by depleting PSMD1, 6, and 11, the subunits of the 19S proteasome regulatory complex. Given the addiction of the many cancer types to a high 26S/20S ratio, the depletion strategy is highly effective in killing many aggressive cancer cell lines but not mouse and human immortalized and normal cells.

Methods

We used two aggressive cell lines, MDA‐MB‐231, a triple‐negative breast tumor cell line, and OVCAR8, a high‐grade ovary adenocarcinoma. Cell culture, mouse MDA‐MB‐231, OVCAR8 xenografts, and patient‐derived ovarian cancer xenograft (PDX) models were transduced with lentivectors expressing PSMD1 shRNA. Tumor size was measured to follow treatment efficacy.

Results

Using different experimental strategies of expressing shRNA, we found that PSMD1 depletion, either by expressing PSMD1 shRNA in an inducible manner or in a constitutive manner, robustly inhibited MDA‐MB‐231, and OVCAR8 xenograft tumor growth. Furthermore, the PSMD1 depletion strategy compromised the growth of the PDX of primary ovarian cancer.

Conclusion

Our results suggest that reducing the 26S/20S ratio might be a valuable strategy for treating drug‐resistant aggressive types of cancers.
Prognostic risk factor of major salivary gland carcinomas and survival prediction model based on random survival forests
Authors: Chen Yufan , Li Guoli , Jiang Wenmei , Nie Rong Cheng , Deng Honghao , Chen Yingle , Li Hao , Chen Yanfeng
Published: March 2023

Salivary gland malignancies are rare and are often acompanied by poor prognoses. So, identifying the populations with risk factors and timely intervention to avoid disease progression is significant. This study provides an effective prediction model to screen the target patients and is helpful to construct a cost‐effective follow‐up strategy. We enrolled 249 patients diagnosed with salivary gland tumors and analyzed prognostic risk factors using Cox proportional hazard univariable and multivariable regression models. The patients' data were split into training and validation sets on a 7:3 ratio, and the random survival forest (RSF) model was established using the training sets and validated using the validation sets. The maximally selected rank statistics method was used to determine a cut point value corresponding to the most significant relation with survival. Univariable Cox regression suggested age, smoking, alcohol consumption, untreated, neural invasion, capsular invasion, skin invasion, tumors larger than 4 cm, advanced T and N stage, distant metastasis, and non‐mucous cell carcinoma were risk factors for poor prognosis, and multivariable analysis suggested that female, aging, smoking, untreated, and non‐mucous cell carcinoma were risk factors. The time‐dependent ROC curve showed the AUC of the RSF prediction model on 1‐, 2‐, and 3‐year survival were 0.696, 0.779, and 0.765 respectively in the validation sets. Log‐rank tests suggested that the cut point 7.42 risk score calculated from the RSF was most effective in dividing patients with significantly different prognoses. The prediction model based on the RSF could effectively screen patients with poor prognoses.
A systematic review of neoadjuvant and definitive immunotherapy in locally advanced head and neck squamous cell carcinoma
Authors: Nindra Udit , Hurwitz Joshua , Forstner Dion , Chin Venessa , Gallagher Richard , Liu Jia
Published: March 2023

Background

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) require multi‐modality treatment. Immune checkpoint inhibitors (ICIs) are now standard of care in management of recurrent/metastatic HNSCC. However, its role in the definitive and neoadjuvant setting remains unclear.

Methods

A literature search was conducted that included all articles investigating ICI in untreated locally advanced (LA) HNSCC. Data was extracted and summarised and rated for quality using the Cochrane risk of bias tool.

Results

Of 1086 records, 29 met the final inclusion criteria. In both concurrent and neoadjuvant settings, the addition of ICI was safe and did not delay surgery or reduce chemoradiotherapy completion. In the concurrent setting, although ICI use demonstrates objective responses in all published trials, there has not yet been published data to with PFS or OS benefit. In the neoadjuvant setting, combination ICI resulted in superior major pathological response rates compared to ICI monotherapy without a significant increase adverse event profiles, but its value in improving survival is not clear. ICI efficacy appears to be affected by tumour characteristics, in particular PD‐L1 combined positive score, HPV status and the tumour microenvironment.

Conclusions

There is significant heterogeneity of ICI use in untreated LA HNSCC with multiple definitive concurrent and neoadjuvant protocols used. Resultantly, conclusions regarding the survival benefits of adding ICI to standard‐of‐care regimens cannot be made. Further trials and translational studies are required to elucidate optimal ICI sequencing in the definitive setting as well as better define populations more suited for neoadjuvant protocols.
Peripheral lymphocyte fluctuation as an indicator of severe immune‐related adverse events in patients treated with immune checkpoint inhibitors
Authors: Haraguchi Masafumi , Nakao Yasuhiko , Narita Syouhei , Matsumoto Kousuke , Fukushima Masanori , Sasaki Ryu , Honda Takuya , Miuma Satoshi , Miyaaki Hisamitsu , Nakao Kazuhiko
Published: March 2023

Aim

Immune checkpoint inhibitors (ICIs) have proven to be effective treatments for various cancers, but can also elicit immune‐related adverse events (irAEs). Given that severe irAEs can be life‐threatening, biomarkers that can predict the occurrence of irAEs are of paramount importance. ICIs affect the dynamics of lymphocytes, and alterations in these dynamics may play a role in the development and severity of irAEs. The aim of this study was to investigate the correlation between irAEs and changes in lymphocyte counts.

Methods

Information on irAEs was collected from 226 ICI cases from 2014 to 2020. We compared lymphocyte counts before treatment and at the onset of irAE and investigated the association between lymphocyte count fluctuations and the presence and severity of irAE, the course after steroid treatment, and overall survival.

Results

Of the 226 cases, 27 patients developed grade 3 or higher irAE. Compared to the other groups, the lymphocyte count in this group was significantly decreased at the time of irAE (p < 0.01). There was a trend toward a rapid increase in lymphocyte count in the steroid responder group compared to the non‐responder group. Regarding overall survival, patients with irAE had significantly longer survival than those without irAE (p = 0.0025). However, there was no association between changes in lymphocyte count and survival in patients with irAE.

Conclusion

The percentage change in lymphocyte count was found to correlate with the incidence of severe irAEs. Close monitoring of the patient's condition is crucial when the lymphocyte count decreases during ICI treatment.
MicroRNA‐17‐3p protects against excessive posthypoxic autophagy in H9C2 cardiomyocytes via PTEN–Akt–mTOR signaling pathway
Authors: He Yi , Zhang Dengwen , Zhang Qingqing , Cai Yin , Huang Chongfeng , Xia Zhengyuan , Wang Sheng
Published: March 2023

The activity of phosphatase and tensin homolog (PTEN) can be inhibited by miR‐17‐3p, which results in attenuating myocardial ischemia/reperfusion injury (IRI), however, the mechanism behind this phenomenon is still elusive. Suppression of PTEN leads to augmented protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling strength and constrained autophagy activation, which might be the one mechanism for the ameliorated myocardial IRI. Thus, we tested the hypothesis that miR‐17‐3p attenuated hypoxia/reoxygenation (H/R)‐mediated damage in cardiomyocytes by downregulating excessive autophagy via the PTEN–Akt–mTOR axis. The expression of miR‐17‐3p was remarkably increased after H/R treatment (6‐h hypoxia followed by 6‐h reoxygenation; H6/R6), which was concomitant with the increase of the release of lactic acid dehydrogenase (cell injury marker) and the enhancement LC3II/I ratio (autophagy markers) in H9C2 cardiomyocytes. Ectoexpression of miR‐17‐3p agomir led to remarkable augmentation of miR‐17‐3p expression and evidently attenuated H/R‐mediated cell damage and excessive autophagy. Furthermore, an increase in miR‐17‐3p expression elicited constrained phosphorylation of PTEN (Ser380) while enhanced the phosphorylation of Akt (Thr308, Ser473) and mTOR (Ser536) after H/R stimulation. In addition, pretreatment with LY‐294002 (an Akt selective inhibitor) and rapamycin (an mTOR selective inhibitor) significantly abrogated the protective function of miR‐17‐3p on H/R‐mediated cell damage and autophagy in H9C2 cardiomyocytes. Taken together, these observations indicated that the enhancement of the PTEN/Akt/mTOR axis and the consequent suppression of autophagy overactivation might represent an underlying mechanism by which miR‐17‐3p attenuated H/R‐mediated damage in H9C2 cells.
Exosomes in COVID‐19 infection: Focus on role in diagnosis, pathogenesis, immunity, and clinical trials
Authors: Aljuhani Alhanouf , Albalawi Omniah , Albalawi Rahaf , Alsalama Reem , Alatawi Safyah , Altemani Reem , Abdel‐Maksoud Mohamed S. , Elsherbiny Nehal
Published: March 2023

Since the end of 2019, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has spread as a new strain of coronavirus disease (COVID‐19) and progressed as a global pandemic. Exosomes are membrane‐bound vesicles released from almost all cells and are crucially involved in cell–cell communication. Interestingly, COVID‐19 viral particles produce exosomes that moderate communication between infected and uninfected cells. Hence, there is growing evidence highlighting the crucial implications of exosomes in COVID‐19 infection, transmission, intercellular spread, and reinfection. On the other hand, clinical trials have demonstrated mesenchymal stem cell‐derived exosomes as a promising therapeutic strategy for severely affected COVID‐19 patients. Also, convalescent plasma‐derived exosomes have been proposed for multiple efficacies in COVID‐19 patients. Furthermore, messenger RNAs (mRNA)‐loaded exosomes were superior to mRNA‐loaded lipid nanoparticles as a delivery system. Hence, exosomes can be used to safely induce SARS‐CoV‐2 immunity via their loading with mRNAs encoding immunogenic forms of SARS‐CoV‐2 spike and nucleocapsid proteins. Moreover, exosomes can be used as a nano‐delivery system for microRNA to alleviate cytokine storm and prevent the progression of organ failure in COVID‐19 patients. The present review summarizes state of the art concerning the role of exosomes in COVID‐19 infection and accompanying organ complications as well as the potential use of exosomes in COVID‐19 diagnosis, treatment, drug delivery, and vaccination. The review also sheds the light on the common biogenic pathway between the SARS‐CoV‐2 virus and exosomes. Additionally, the latest and current clinical trials using exosomes for COVID‐19 infection are summarized.
Unraveling the connection between calreticulin and myeloproliferative neoplasms via calcium signaling
Authors: Jaiswal Amit , Wang Zhiguo , Xudong Zhu , Ju Zhenyu
Published: March 2023

Mutations in the form of insertions and deletions (INDEL) in the calreticulin gene lead to essential thrombocythemia (ET) which is characterized by the formation of thrombosis. However, the connection between calreticulin INDEL and ET remains largely elusive. Through combined molecular dynamics simulation, clustered regularly interspaced short palindromic repeats (CRISPR) and calcium imaging studies on the wild type and mutated isoforms of calreticulin, the mechanism underlying the calreticulin INDEL induced ET was investigated at the molecular level. Our results demonstrate that mutations in exon‐9 could lead to significant conformational variations of calreticulin structure and thereby reducing its interaction with calcium ions due to decreased electrostatic contributions. The consequence of mutations on calreticulin's structural integrity was revealed by identifying the key residues and their roles in calcium binding. Furthermore, mutations implemented by CRISPR‐Cas9 in exon‐9 showed diminished calcium signaling in HEK‐293T cells, which agree well with our in‐silico findings. The current study might help in understanding the variations of molecular interactions between calreticulin's exon‐9 and calcium ions during physiological and pathological conditions. The results might also provide useful information for designing novel therapeutic approaches targeting ET.
The roles of ATP‐binding cassette transporter A1 and its substrate cholesterol in head and neck cancers
Authors: Sanli Fatma , Karatas Omer F.
Published: March 2023

Head and neck cancer (HNC), which is among the deadliest malignancies, is the seventh most common cancer worldwide. How cholesterol homeostasis is linked to human cancers has long been a source of curiosity. One of the few proteins that are involved in cholesterol homeostasis is ATP‐binding cassette transporter A1 (ABCA1), which is broadly expressed in numerous tissues. ABCA1 increases cholesterol efflux, inhibits cholesterol deposition in cells, and modulates anticancer activities. Therefore, it is not surprising that decreased ABCA1 activity and altered cholesterol homeostasis are implicated in the patho‐physiology of HNCs. In this review, we focus on the role of cholesterol metabolism in the patho‐physiology and progression of HNCs, with an emphasis on biological effects of ABCA1 transporters. We also review therapeutic approaches targeting cholesterol metabolism, as well as how combining such approaches with existing anticancer treatments may have synergistic effects and therefore open up new therapeutic avenues.
Looking but not seeing the cap: The case for PROGRESS‐CTO
Authors: Tarantini Giuseppe , Cardaioli Francesco
Published: March 2023

Key Points

Chronic total occlusion (CTO) procedures are a well‐established treatment strategy for selected patients with chronic coronary disease. Proximal cap ambiguity is one of the key aspects impacting procedural success and final results.

In this issue of CCI, data from a large multicenter prospective registry confirmed that proximal cap ambiguity is related to worse procedural outcomes, more aggressive procedural techniques, and higher rates of procedural complications.

Proximal cap ambiguity should be considered for patients' selection and procedural planning. Further analysis will be needed to test different imaging modalities for a clearer cap visualization.
Angiography‐derived functional assessment of left main coronary stenoses
Authors: Yuasa Sonoka , Lauri Francesco Maria , Mejia‐Renteria Hernan , Liontou Catherine , Lee Hyun‐Jong , Tanigaki Toru , Nakayama Masafumi , Warisawa Takayuki , Uchiyama Takashi , Matsuo Hitoshi , Davies Justin E. , Sato Takao , Escaned Javier
Published: March 2023

Objectives

We aimed to evaluate the diagnostic accuracy of quantitative flow ratio (QFR) in left main (LM) coronary stenoses, using Fractional Flow Reserve (FFR) as reference.

Background

QFR has demonstrated a high accuracy in determining the functional relevance of coronary stenoses in non‐LM. However, there is an important paucity of data regarding its diagnostic value in the specific anatomical subset of LM disease.

Methods

This is a retrospective, observational, multicenter, international, and blinded study including patients with LM stenoses. Cases with significant ostial LM disease were excluded. QFR was calculated from conventional angiograms at blinded fashion with respect to FFR.

Results

Sixty‐seven patients with LM stenoses were analyzed. Overall, LM had intermediate severity, both from angiographic (diameter stenosis [%DS] 43.8 ± 11.1%) and functional perspective (FFR 0.756 ± 0.105). Mean QFR was 0.733 ± 0.159. Correlation between QFR and FFR was moderate (r = 0.590). Positive and negative predictive value, sensitivity and specificity were 85.4%, 64%, 85.4%, and 69.6% respectively. Classification agreement of QFR and FFR in terms of functional stenosis severity was 78.1%. Area under the receiver operating characteristics of QFR using FFR as reference was 0.82 [95% confidence interval [CI], 0.71−0.93], and significantly better than angiographic evaluation including %DS (area under the receiver‐operating characteristic curve [AUC] 0.45 [95% CI, 0.32−0.58], p < 0.001) and minimum lumen diameter (AUC 0.60 [95% CI, 0.47−0.74], p < 0.001).

Conclusions

Compared with FFR, QFR has acceptable diagnostic performance in determining the functional relevance of LM stenosis, being better than conventional angiographic assessment. Nonetheless, caution should be taken when applying functional angiography techniques for the assessment of LM stenosis given its particular anatomical characteristics.
In vivo evaluation of intravascular lithotripsy in a healthy porcine coronary model
Authors: Yin Jiasheng , Wang Rui , Chen Han , Lu Hao , Yang Zhuoran , Xu Fei , Zang Tongtong , Liu Chengpeng , Shen Li , Ge Junbo
Published: March 2023

Objectives

In this study, we aimed to investigate the vascular response to an intravascular lithotripsy (IVL) shockwave balloon in a healthy porcine coronary artery model.

Background

IVL is a novel clinical technique for modifying heavily calcified atherosclerotic plaques.

Methods

A total of 24 porcine coronary arteries were treated with IVL or plain old balloon angioplasty (POBA). Histology, histomorphometry, quantitative coronary angiography analysis (QCA), and optical coherence tomography (OCT) were performed postprocedure and at 1‐month follow‐up (1M‐FU).

Results

There was no significant difference in the late lumen loss and diameter stenosis (determined by QCA) and the minimal lumen area (evaluated by OCT) of the IVL and POBA groups at 1M‐FU. Pathological analysis revealed that the lumen and neointima areas were similar between the two groups. However, the medial and adventitial layers were more prominent in the IVL than in the POBA group. The injury score and inflammation of the media and adventitia increased dramatically in the IVL group postprocedure and at 1M‐FU. At 1M‐FU, media fibrin deposition and adventitial fibrosis were also significantly increased in the IVL group. However, there was no significant difference in neointima fibrin deposition, endothelialization, and thrombosis between both groups. Layered separation of the media and adventitia was observed in the IVL group.

Conclusion

The findings indicate that the IVL balloon did not cause serious intimal hyperplasia and endothelial damage compared with the effects of POBA in the healthy coronary artery. However, shock waves may cause unique damage to the vascular media and adventitia in the coronary artery, which was not observed in the peripheral artery.
Calcified coronary nodule: Tip of the iceberg on a road full of thorns
Authors: Grines Cindy L. , Tummala Pradyumna E.
Published: March 2023

Key Points

Nodular coronary calcium (NC) is infrequent, is associated with advanced age and chronic kidney disease and may be responsible for acute coronary syndromes.

NC leads to a greater incidence of stent malapposition and target lesion revascularization, and intravascular imaging often shows recurrence of the calcified nodule within the stent.

Clinical outcomes are worse after stenting lesions with calcified nodules, but randomized studies are necessary to determine the best management strategy.
PROTOCOL: Evaluating the application and effectiveness of precision teaching: A systematic review and meta‐analysis
Authors: Vostanis Athanasios , Thompson Paul A. , Padden Ciara , Rizos Konstantinos , Langdon Peter E.
Published: March 2023

Precision Teaching is a behavior measurement system that emphasizes the development of behavioral repertoires and utilizes Standard Celeration Charts as its primary tool. This system has been applied across various areas, including mainstream and special education, and has successfully improved academic, motor, communication, and other skills. While previous systematic reviews have highlighted important aspects of Precision Teaching, a more comprehensive evaluation is needed to consider all its different applications and recent developments in conceptualizing it. Therefore, this systematic review and meta‐analysis will assess the effectiveness of Precision Teaching in accelerating human behavior, identify all the areas of its application, and review the technical aspects of its implementation. The review aims to provide a comprehensive understanding of the system and its potential benefits for individuals in different settings.
Malocclusions and oral dysfunctions: A comprehensive epidemiological study on 359 schoolchildren in France
Authors: Borsa Leslie , Estève Déborah , Charavet Carole , Lupi Laurence
Published: March 2023

Objectives

The purpose was to conduct a comprehensive study of malocclusions and oral dysfunctions on 11‐year‐old children and to study the risk factors associated with malocclusions.

Material and Methods

A cross‐sectional descriptive epidemiological survey was conducted among 359 children in France. A clinical examination was conducted, and orthodontic and oral functional data were collected. In addition, the need for orthodontic treatment was evaluated using the criteria defined by of the French National Authority for Health (HAS). Finally, a univariate and multivariate analysis was performed to assess the risks associated with malocclusions.

Results

Most children (88%) exhibited a malocclusion, regardless of gender (p = .912). The examination of oral functions identified a large number of swallowing (87%) and respiration (42.7%) disorders. The presence of malocclusion was statistically linked to the low position of the tongue at rest (p < .001), abnormal swallowing (p = .03), and improper mouth breathing (p = .001). After a multivariate analysis, the type of respiration (odds ratio [OR] = 3.2 [1.4–7.3]) and the position of tongue at rest (OR = 3.43 [1.7–7.1]) were the two most prominent factors in the prediction of emerging malocclusion.

Conclusion

This epidemiological survey reveals a high prevalence of dental malocclusions and functional disorders. Oral respiration and the low position of the tongue at rest are the most important factors in the prediction of a malocclusion.
How to explain stock returns of utility companies from an environmental, social and corporate governance perspective
Authors: López‐Cabarcos M. Ángeles , Santos‐Rodrigues Helena , Quiñoá‐Piñeiro Lara , Piñeiro‐Chousa Juan
Published: March 2023

Sustainability is a major challenge in today's business world, making environmental, social and governance criteria an indispensable tool for business management and investment decisions. Using 2020 data of 47 companies from the STOXX Europe Total Market Utilities Index and qualitative comparative analysis, this study aims to analyse how the combination of CO2 equivalent emissions, sustainability compensation incentives, environmental investments, environment management training, and policy fair competition leads to utility companies' stock market returns. Two subsample models (electricity and non‐electricity utilities) have been considered in the study. The results point to the absence of CO2 equivalent emissions, the absence of incentives, and the presence of environmental investment as key variables to lead to stock market returns. The findings provide relevant information for managers and practitioners of utilities industry to achieve improvements in the environmental, social and governance management practices, maintaining profitability in financial markets and facilitating decision‐making for investors.
A double boost 9‐level switched capacitor‐based multilevel inverter for photovoltaic applications
Authors: Agarwal Ritika , Gupta Krishna Kumar , Singh Shakti
Published: March 2023

A self‐balancing 9‐level inverter is proposed in this paper. To generate a 9‐level voltage with a gain of two requires a single DC source, eight power switches, three capacitors, and two diodes. Without additional circuitry, the voltages of the capacitors in the proposed topology can achieve inherent balance. The peak‐inverse‐voltage (PIV) of six power switches equals or less than the source voltage, and the other two are twice. As power switches are complementary, the proposed topology requires fewer gate drivers. Furthermore, the self‐balancing capability of capacitors' voltage helps in simple control complexity. The description of topology, mode of operation, modulation strategy, and design of the capacitor of proposed topology are presented. The advantages of the proposed inverter are examined by comparing it with switched capacitor multilevel inverters (MLIs). Finally, a 9‐level prototype is built to verify the theoretical analysis and the practical efficacy of the proposed inverter.
Local and landscape environmental heterogeneity drive ant community structure in temperate seminatural upland grasslands
Authors: Pérez‐Sánchez Antonio J. , Schibalski Anett , Schröder Boris , Klimek Sebastian , Dauber Jens
Published: March 2023

Environmental heterogeneity is an important driver of ecological communities. Here, we assessed the effects of local and landscape spatial environmental heterogeneity on ant community structure in temperate seminatural upland grasslands of Central Germany. We surveyed 33 grassland sites representing a gradient in elevation and landscape composition. Local environmental heterogeneity was measured in terms of variability of temperature and moisture within and between grasslands sites. Grassland management type (pasture vs. meadows) was additionally included as a local environmental heterogeneity measure. The complexity of habitat types in the surroundings of grassland sites was used as a measure of landscape environmental heterogeneity. As descriptors of ant community structure, we considered species composition in terms of nest density, community evenness, and functional response traits. We found that extensively grazed pastures and within‐site heterogeneity in soil moisture at local scale, and a high diversity of land cover types at the landscape scale affected ant species composition by promoting higher nest densities of some species. Ant community evenness was high in wetter grasslands with low within‐site variability in soil moisture and surrounded by a less diverse landscape. Fourth‐corner models revealed that ant community structure response to environmental heterogeneity was mediated mainly by worker size, colony size, and life history traits related with colony reproduction and foundation. We discuss how within‐site local variability in soil moisture and low‐intensity grazing promote ant species densities and highlight the role of habitat temperature and humidity affecting community evenness. We hypothesize that a higher diversity of land cover types in a forest‐dominated landscape buffers less favorable environmental conditions for ant species establishment and dispersal between grasslands. We conclude that spatial environmental heterogeneity at local and landscape scale plays an important role as deterministic force in filtering ant species and, along with neutral processes (e.g., stochastic colonization), in shaping ant community structure in temperate seminatural upland grasslands.
Spatial–temporal variations in vegetation with changing water stress in the Kongqi River basin, China
Authors: Zhang Haoyue , Wang Xu‐Sheng , Zhang Jun , Gu Xiaofan , Yin Lihe , Yeh Pat J.‐F.
Published: March 2023

Identifying dominant water stress on vegetation growth over the arid basins is essential to better understand ecosystems and water interactions, which are fundamental in managing regional water resources. The Kongqi River basin is an ecologically sensitive area with limited water resources in the northern part of Tarim Basin in northwest China. How is the spatial distribution of vegetation controlled by natural conditions and anthropogenic regulation of water resources is a concern for ecology system protection. This study explores the spatio–temporal variations in the remote‐sensing vegetation index across the basin and identifies water stress forces with the Mann–Kendall trend test and linear regression analysis. Results show that the controls of vegetation change are different among geomorphological units over the past 20 years. In the northern mountains, the increasing vegetation trend mainly responds to climate change, particularly to increased precipitation. In contrast, in the plain area, the vegetation change is controlled by changes in hydrologic and anthropogenic water stresses. A significant rise in surface water and groundwater utilization counteracts the negative effect of the increasing hydrologic water stress in the upstream oasis. However, the increasing anthropogenic water stress contributed to more than 50% of vegetation decay in the downstream area during 2004–2015. The ecological water conveyance beginning in 2016 has promoted vegetation restoration, but the effect decreased with distance to the upstream area and showed a delay in response. This study provides evidence for ecological consequence of anthropogenic water stress that is beneficial to improve water resources management and ecosystem restoration.
Heart failure with reduced ejection fraction and atrial fibrillation: a Sub‐Saharan African perspective
Authors: Mboweni Nonkanyiso , Maseko Muzi , Tsabedze Nqoba
Published: March 2023

Cardiovascular diseases are a well‐established cause of death in high‐income countries. In the last 20 years, Sub‐Saharan Africa (SSA) has seen one of the sharpest increases in cardiovascular disease‐related mortality, superseding that of infectious diseases, including HIV/AIDS, in South Africa. This increase is evidenced by a growing burden of heart failure and atrial fibrillation (AF) risk factors. AF is a common comorbidity of heart failure with reduced ejection fraction (HFrEF), which predisposes to an increased risk of stroke, rehospitalizations, and mortality compared with patients in sinus rhythm. AF had the largest relative increase in cardiovascular disease burden between 1990 and 2010 in SSA and the second highest (106.4%) increase in disability‐adjusted life‐years (DALY) between 1990 and 2017. Over the last decade, significant advancements in the management of both HFrEF and AF have emerged. However, managing HFrEF/AF remains a clinical challenge for physicians, compounded by the suboptimal efficacy of guideline‐mandated pharmacotherapy in this group of patients. There may be an essential role for racial differences and genetic influence on therapeutic outcomes of HFrEF/AF patients, further complicating our overall understanding of the disease and its pathophysiology. In SSA, the lack of accurate and up‐to‐date epidemiological data on this subgroup of patients presents a challenge in our quest to prevent and reduce adverse outcomes. This narrative review provides a contemporary overview of the epidemiology of HFrEF/AF in SSA. We highlight important differences in the demographic and aetiological profile and the management of this subpopulation, emphasizing what is currently known and, more importantly, what is still unknown about HFrEF/AF in SSA.
Analysis of DNA methylation markers for tissue identification in individuals with different clinical phenotypes
Authors: Silva Deborah S. B. S. , Ecker Haley , Walcott Johnisa , Weeden Rebecca , Medina Adriana , Gorson Juliette M.
Published: March 2023

Deoxyribonucleic acid (DNA) methylation patterns can be used to identify the type of tissue or body fluid found at a crime scene. However, tissue‐related methylation levels have not been analyzed in individuals with different illnesses and medical conditions in forensic‐specific studies. The primary goal of this study was to investigate if certain clinical phenotypes can alter the methylation levels of CpG sites in genes involved in tissue typing. Four studies with focus on DNA methylation analysis on individuals with different clinical conditions were selected from the Gene Expression Omnibus database. Then, a list of 137 CpG sites was compiled for further investigation. Statistical tests were performed to compare the beta‐values results obtained for the control groups and the individuals affected by medical conditions. For each study, CpG sites that presented significant statistical differences between patients and control group were identified and it was possible to notice that DNA methylation levels can be affected in sites with potential forensic use. Although the observed DNA methylation variation (less than 10% difference) in this study would likely not cause any issues in body fluid identification, the results are important to show that this type of analysis should be taken into consideration when investigating and further validating body fluid markers. The CpG sites identified in this study should be further investigated by future studies on body fluids identification, and due to the significant difference in methylation levels in samples from affected individuals, caution must be taken before including these sites in tissue identification investigations.
Parental dieting impacts inpatient treatment outcomes for adolescents with restrictive eating disorders
Authors: Duck Sarah Ann , Guarda Angela S. , Schreyer Colleen C.
Published: March 2023

Objective

Parental feeding practices and disordered eating are potential risk factors for the development of disordered eating in children and adolescents. This study measured the relationship between parental dieting behaviours and inpatient treatment outcomes for adolescents with restrictive eating disorders (EDs).

Method

Parents of adolescents with restrictive EDs (N = 45) admitted to a specialty integrated inpatient‐partial hospital meal‐based ED treatment programme completed questionnaires assessing parental eating and exercise behaviours. Adolescent clinical data, including percentage median body mass index (%mBMI) at admission and discharge and rate of weight gain, were abstracted from the electronic medical record.

Results

Adolescents whose parents reported dieting had a slower rate of weight gain (3.47 lbs./week) compared to participants whose parents were not dieting (4.54 lbs./week; p = 0.017). Additionally, participants whose parents reported dieting had a lower %mBMI at programme discharge (M = 93.56) than participants whose parents did not report dieting (M = 95.99; p = 0.033).

Conclusion

Parental dieting behaviours may impact an adolescent's response to inpatient ED treatment. Findings suggest a need to assess parental dieting behaviour, and when appropriate, provide additional psychoeducation regarding the potential risks of weight or shape‐focussed dialogue and the benefits of modelling adaptive meal behaviours.