bluuebunny/crossref_metadata_2025 huggingface dataset:
A Reexamination of PLEDs in the Setting of Status Epilepticus
Authors: Boggs Jane
Published: December 2022

Serial EEG During Human Status Epilepticus: Evidence for PLED as an Ictal Pattern

Garzon E, Fernandes RM, Sakamoto AC

Neurology 2001;57:1175–1183

Objective

To analyze the relationship between periodic lateralized epileptiform discharges (PLED) and status epilepticus (SE), to evaluate the relationship between mortality and periodic patterns, and to determine whether a stereotypic sequence of EEG patterns exists during human SE.

Methods

The authors performed a prospective clinical and electrographic study comprising 62 episodes of SE, 55 patients, and 254 ictal/postictal EEG recordings. Serial daily EEG were obtained in all cases.

Results

Partial SE was the predominant clinical type. Four distinct ictal EEG patterns were identified: intermittent EEG seizures (IES), merging EEG seizures (MES), continuous ictal discharges (CID), and periodic epileptiform discharges (PED) which could be lateralized (PLED) or bilateral (PBED). IES was the most common ictal pattern. In the same record, only one combination of ictal patterns was observed corresponding to an association of PLED or PBED and MES pattern. Serial EEG demonstrated that approximately one-third of SE resolved before the second EEG, another one-third persisted and maintained the same ictal pattern throughout the entire evolution, and the final one-third showed variable ictal EEG patterns. PLED were also unequivocally associated with epileptic seizures, and in some patients were the initial ictal pattern.

Conclusion

PLED can be an ictal pattern; and, in contrast to previous observations, no stereotyped sequence of ictal EEG patterns was found. PLED/PBED were not a terminal ictal pattern in every case, and outcome was more related to age and etiology than to specific ictal EEG patterns.
Grafts of Encapsulated Fibroblasts Engineered to Release an Anticonvulsant Substance
Authors: Scharfman Helen
Published: December 2022

Grafts of Adenosine-releasing Cells Suppress Seizures in Kindling Epilepsy

Huber A, Padrun V, Deglon N, Aebischer P, Mohler H, Boison D

Proc Natl Acad Sci U S A 2001;98:7611–7616

Adenosine is an inhibitor of neuronal activity in the brain. The local release of adenosine from grafted cells was evaluated as an ex vivo gene therapy approach to suppress synchronous discharges and epileptic seizures. Fibroblasts were engineered to release adenosine by inactivating the adenosine-metabolizing enzymes adenosine kinase and adenosine deaminase. After encapsulation into semipermeable polymers, the cells were grafted into the brain ventricles of electrically kindled rats, a model of partial epilepsy. Grafted rats provided a nearly complete protection from behavioral seizures and a near-complete suppression of after discharges in electroencephalogram recordings, whereas the full tonic-clonic convulsions in control rats remained unaltered. Thus, the local release of adenosine resulting in adenosine concentrations <25 nM at the site of action is sufficient to suppress seizure activity and, therefore, provides a potential therapeutic principle for the treatment of drug-resistant partial epilepsies.
Widespread Neuronal Dysfunction in Temporal Lobe Epilepsy
Authors: Cascino Gregory D.
Published: December 2022

Reduced Extrahippocampal NAA in Mesial Temporal Lobe Epilepsy

Mueller SG, Suhy J, Laxer KD, Flenniken DL, Axelrad J, Capizzano AA, Weiner MW

Epilepsia 2002;43(10):1210–1216

Purpose

Structural and metabolic abnormalities in the hippocampal region in medial temporal lobe epilepsy (mTLE) are well described; less is known about extrahippocampal changes. This study was designed to characterize extrahippocampal metabolic abnormalities in mTLE with magnetic resonance spectroscopy in combination with tissue segmentation and volumetry of gray and white matter.

Methods

Multislice magnetic resonance spectroscopic imaging (1H-MRSI) in combination with tissue segmentation was performed on 16 patients with mTLE and 12 age-matched healthy volunteers. The data were analyzed by using a regression-analysis model that estimated the metabolite concentrations in 100% cortical gray and 100% white matter in the frontal lobe and nonfrontal brain. The segmented image was used to calculate the fraction of gray and white matter in these regions.

Results

mTLE had significantly lower N-acetyl aspartate (NAA) in ipsi- and contralateral frontal gray ( P = 0.03) and in ipsi- and contralateral nonfrontal white matter ( P = 0.008) compared with controls. Although there were no associated volumetric deficits in frontal gray and white matter, ipsilateral nonfrontal gray matter ( P = 0.003) was significantly smaller than that in controls.

Conclusions

mTLE is associated with extrahippocampal metabolic abnormalities and volumetric deficits, but these do not necessarily affect the same regions.
Childhood Temporal Lobectomy: Results of Extended Follow-Up
Authors: Marks William J.
Published: December 2022

Long-term Follow-up of Temporal Lobectomy in Children

Jarrar RG, Buchhalter JR, Meyer FB, Sharbrough FW, Laws E

Neurology 2002;59:1635–1637

Temporal lobectomy is an effective treatment for medically intractable seizures. The change in seizure status with prolonged postoperative follow-up is unclear. The authors followed up 37 patients who underwent first-time temporal lobectomy during childhood for at least 15 years. This study is the longest follow-up of children who have had a temporal lobectomy for intractable seizures. It demonstrates that seizure recurrence can increase with longer duration of follow-up.
Magnetic Resonance Imaging of Familial Temporal Lobe Epilepsy
Authors: Theodore William H.
Published: December 2022

Magnetic Resonance Imaging Evidence of Hippocampal Sclerosis in Asymptomatic, First-Degree Relatives of Patients with Familial Mesial Temporal Lobe Epilepsy

Kobayashi E, Li LM, Lopes-Cendes I, Cendes F

Arch Neurol 2002;59:1891–1894

Purpose

To investigate the presence of hippocampal atrophy (HA) and other magnetic resonance imaging (MRI) signs of hippocampal sclerosis (HS) in asymptomatic relatives of patients with familial mesial temporal lobe epilepsy (FMTLE).

Methods

We invited first-degree, asymptomatic relatives of patients with FMTLE to participate in our MRI protocol. After informed consent, all participating individuals underwent an MRI examination. Hippocampal abnormality was determined by qualitative and volumetric analyses, using a standard protocol.

Results

We studied 52 asymptomatic individuals (27 men), with a mean age of 32 years (range, 7–71 years), from 11 families with FMTLE. Volumetric studies showed HA in 18 (34%) of 52 individuals: 11 had left HA, and seven had bilateral HA. In addition, careful visual analysis of T1- and T2-weighted images showed additional classic MRI signs of HS (such as abnormal T2 signal and/or abnormal internal structure) in 14 of these 18 individuals. There was no age difference between individuals with and without HA ( t test, P = 0.80).

Conclusions

Our findings indicate that MRI evidence of HS is not necessarily related to seizure severity and may occur in individuals who never had seizures. In addition, these observations strongly indicate that HS in FMTLE is not a consequence of recurrent seizures and is determined by a strong genetic predisposition. The determination of seizure severity in patients with FMTLE probably depends on the interaction of different factors, both genetic and environmental.
Radical Ideas about Seizure-Induced Neuronal Damage
Authors: Stafstrom Carl E.
Published: December 2022

Free Radical–Mediated Cell Damage After Experimental Status Epilepticus in Hippocampal Slice Cultures

Kovács R, Schuchmann S, Gabriel S, Kann O, Kardos J, Heinemann U

J Neurophysiol 2002:88:2909–2918

Generation of free radicals may have a key role in the nerve cell damage induced by prolonged or frequently recurring convulsions (status epilepticus). Mitochondrial function also may be altered because of production of free radicals during seizures. We therefore studied changes in field potentials (fp) together with measurements of extracellular, intracellular, and intramitochondrial calcium concentration ([Ca2+]e, [Ca2+]i, and [Ca2+]m, respectively), mitochondrial membrane potential (ΔΨ), nicotinamide adenine dinucleotide phosphate [NAD(P)H] autofluorescence, and dihydroethidium (HEt) fluorescence in hippocampal slice cultures by means of simultaneous electrophysiologic and microfluorimetric measurements. As reported previously, each seizure-like event (SLE) resulted in mitochondrial depolarization associated with a delayed increase in oxidation of HEt to ethidium, presumably indicating reactive oxygen species (ROS) production. We show here that repeated SLEs led to a decline in intracellular and intramitochondrial Ca2+ signals despite unaltered Ca2+ influx. Mitochondrial depolarization and the NAD(P)H signal became smaller during recurring SLEs. By contrast, the ethidium fluorescence increases remained constant or even increased from SLE to SLE. After about 15 SLEs, activity changed to continuous afterdischarges with steady depolarization of mitochondrial membranes. Staining with a cell-death marker, propidium iodide, indicated widespread cell damage after 2 hours of recurring SLEs. The free radical scavenger, α-tocopherol, protected the slice cultures against this damage and also reduced the ongoing impairment of NAD(P)H production. These findings suggest involvement of an ROS of mitochondrial origin in the epileptic cell damage and that free radical scavenging may prevent status epilepticus–induced cell loss.
Individual “alveolar phenotype” limits dimensions of lateral bone augmentation
Authors: Quirynen Marc , Lahoud Pierre , Teughels Wim , Cortellini Simone , Dhondt Rutger , Jacobs Reinhilde , Temmerman Andy
Published: December 2022

Aim

Alveolar ridge resorption following tooth extraction often renders a lateral bone augmentation inevitable. Some patients, however, suffer from severe early (during graft healing, Eres) and/or late (during follow‐up, Lres) graft resorption. We explored the hypothesis that the “individual phenotypic dimensions” may partially explain the degree of such resorptions.

Materials and Methods

Patients who underwent a guided bone regeneration (GBR) procedure were screened for inclusion according to the following criteria: (1) a relatively symmetrical maxillary arch; (2) an intact contra‐lateral alveolar bone dimension; (3) the availability of a pre‐operative cone‐beam CT (CBCT); (4) a CBCT taken immediately after GBR, and (5) at least one CBCT scan ≥6 months after surgery. CBCT scans from different timepoints were registered and imported into the Mimics software (Materialise, Leuven, Belgium). Bone dimensions of the contra‐lateral site of the augmentation, representing the “individual phenotypical dimension (IPD) of the alveolar crest”, were superimposed on the augmented site and registered accordingly. As such, Eres and Lres could be measured over time, in relation to the IPD (in two dimensions; per millimetre apically from the alveolar crest, in the centre of the GBR), as well as in three dimensions (the entire GBR, 2 mm away from the mesial, distal, and apical border for standardization).

Results

A total of 17 patients (23 augmented sites) were included. After Eres, the outline of the augmentation was in general located ±1 mm outside the IPD, but ≥1.5 years after GBR, it further moved towards the IPD (85% within 0.5 mm distance).

Conclusions

Within the limitations of this study, the results indicate that the dimensions of a lateral bone augmentation are defined by the “individual phenotypic bone boundaries” of the patient.
Have extraction patterns in German adults with severe periodontitis changed between 2000 and 2010? Results from two cohort studies
Authors: Rug Joey , Holtfreter Birte , Völzke Henry , Kocher Thomas
Published: December 2022

Aim

The aim of this study was to evaluate whether extraction thresholds in persons with severe periodontitis have changed between 2000 and 2010 and whether potential shifts have contributed to the reported decrease in tooth extractions in German adults over the last decades.

Materials and Methods

Data from two German population‐based cohort studies in Northeast Germany (Studies of Health in Pomerania; SHIP‐START [baseline 1997–2001; 11‐year follow‐up] and SHIP‐TREND [baseline 2008–2012; 7‐year follow‐up]) were used. In SHIP‐START (SHIP‐TREND), 522 (478) participants with severe periodontitis according to the CDC/AAP case definition were included. Patterns of maximum probing depth (PD) and maximum clinical attachment level (CAL) for retained and extracted teeth were compared between SHIP‐START and SHIP‐TREND participants.

Results

No major differences in patterns of baseline maximum CAL of retained or extracted teeth were detected between SHIP‐START and SHIP‐TREND. Extraction thresholds were identified at the baseline at maximum CAL ≥6 and ≥9 mm. Tooth‐level incidence rates for extraction for baseline maximum CAL of 6 mm were comparable between SHIP‐START and SHIP‐TREND (17.1 vs. 15.9 events per 1000 person‐years).

Conclusions

After a decade, teeth in persons with severe periodontitis were still undergoing extraction with minor or moderate attachment loss. A change in extraction pattern did not contribute to the higher tooth retention rate.
First Language Literacy and Second Language Oracy: A Partial Replication of Foster and Skehan (1996)
Authors: Ryan Jonathon , Foster Pauline , Fester Anthea , Wang Yi , Field Jenny , Kearney Celine , Yap Jia Rong
Published: December 2022

This article responds to calls for greater inclusivity in second language acquisition research and, more specifically, to calls to explore further the impact of first language literacy on second language oracy (e.g., Tarone et al., 2009). We conducted a partial replication of Foster and Skehan's (1996) influential study of task complexity, planning time, and performance over measures of complexity, accuracy, and fluency. The initial study and others had provided robust evidence to suggest that planning time had a positive impact on task performance, particularly for more cognitively demanding tasks. We conducted our replication with adult second language learners with low first language literacy, most of whom were former refugees. Contrary to previous studies, the findings indicate little to no evidence that planning time led to improved linguistic performance. It is not immediately clear why this should be so, and our findings highlight the need for further research with this underrepresented group.
A case of febrile ulceronecrotic Mucha‐Habermann disease responsive to systemic corticosteroids
Authors: Rai Ekra , Kamzan Audrey , Boozalis Emily , Hogeling Marcia , Fong Kelly
Published: December 2022

Febrile ulceronecrotic Mucha‐Habermann disease (FUMHD) is a rare, potentially fatal subtype of pityriasis lichenoides et varioliformis acuta (PLEVA). Herein, we present a rare case of a 14‐year‐old male without significant past medical history who was diagnosed with FUMHD without a clear inciting factor. He was effectively treated with systemic corticosteroids with complete resolution of symptoms.
Measuring policy analytical capacity in renewable energy policy: Germany‐Japan‐US comparison
Authors: Sugiyama Masahiro , Muto Jun
Published: December 2022

Policy makers in the modern age must confront complex and expanding knowledge on a daily basis. It has been put forth that policy making requires increasingly higher levels of policy analytical capacity at the individual, organizational, and system levels. Analytical capacity can enable better policy design and facilitate policy learning. Previous studies mostly operationalized the concept at the individual or organizational level with survey instruments, but the lack of widely and regularly conducted surveys limits the applicability of this method. Here, we propose new indicators of policy analytical capacity at the system level, using publicly available data. Our metrics are based on the outputs such as academic journal publications, government and stakeholder publications, and think‐tank rankings. As an illustration, we apply this approach to the case of renewable energy policies in three countries: Germany, Japan, and the United States. Though each of the underlying metrics is susceptible to uncertainties and biases, a totality of the indicators presents a useful, proxy measurement of policy analytical capacity. The proposed approach can supplement the survey method by enabling longitudinal and geographical investigation into policy analytical capacity.
Highly religious young Catholics in Northern Ireland: Renewing the Catholic landscape?
Authors: Ganiel Gladys
Published: December 2022

This article explores findings from a 2022 survey of students associated with the Catholic Chaplaincy at Queen's University, Belfast. It is the first study to investigate the beliefs, practices, and experiences of highly religious young Catholics in Northern Ireland. It presents survey findings on beliefs, practices, and influences on faith; dynamics of increased religiosity; and views on Church teachings on same sex relationships, euthanasia, sexual relationships, and abortion. Women are more likely to disagree with Church teachings on these issues than men. The survey confirms the importance of family socialization but finds that a substantial minority experience religious change at university. Respondents prioritize renewal but disagree on how to prompt it: some advocate greater ‘openness’ to women, LGBTQ+, and others perceived as marginalized; and others feel ‘evangelization’ should be emphasized. ‘Post‐secular Catholicism’ is used as a foundation for reflections on religious persistence among Northern Ireland's young Catholics, raising questions about their potential role in renewing Ireland's Catholic landscape in light of the synodal process underway in the Church.
Revealing the spatiotemporal characteristics of the general public's panic levels during the pandemic crisis in China
Authors: Chen Yuanyi , Liu Yi , Yan Yingwei
Published: December 2022

The existing crisis management research mostly reveals the patterns of the public's panic levels from the perspectives of public management, sociology, and psychology, only a few studies have revealed the spatiotemporal characteristics. Therefore, this study investigates the spatial distribution and temporal patterns and influencing factors on the general public's panic levels using the Baidu Index data from a geographic perspective. The results show that: (1) The public's panic levels were significantly correlated with the spatial distance between the epicenter and the region of investigation, and with the number of confirmed cases in different regions when the pandemic began to spread. (2) Based on the spatial distance between the epicenter and the region, the public's panic levels in different regions could be divided into three segments: core segment (0–500 km), buffer segment (500–1300 km), and peripheral segment (>1300 km). The panic levels of different people in the three segments were consistent with the Psychological Typhoon Eye Effect and the Ripple Effect can be detected in the buffer segment. (3) The public's panic levels were strongly correlated with whether the spread of the infectious disease crisis occurred and how long it lasted. It is suggested that crisis information management in the future needs to pay more attention to the spatial division of control measures. The type of crisis information released to the general public should depend on the spatial relationship associated with the place where the crisis breaks out.
Todavía no: Justicia, democracia y transición en América Latina
Authors: Benítez Jiménez Maira Ixchel , Guglielmucci Ana , Langa Martínez Laura , López López Érika Liliana , Antillón Najlis Ximena , Ruiz Tovar Ángel , Figueroa Romero Dolores , González Miguel , Saffon María Paula , Marchese Giulia , Vera Lugo Juan Pablo
Published: December 2022

Este libro se pregunta por qué todavía no ha sido posible la justicia en los países latinoamericanos, que afrontan nuevas olas de amnesia, impunidad, represión y violencia, sin que las heridas del pasado hayan sido reparadas aún. Los capítulos exploran cuáles han sido las secuelas de las apuestas programáticas de justicia transicional, más allá de los límites del derecho y la institucionalidad, para reconocer los cambios producidos en los lenguajes, las prácticas, los sentidos, las estrategias, los repertorios políticos y la vida de la gente que, con gran capacidad creativa y de resistencia, anhela superar el pasado violento y conseguir la paz en sus territorios.
Optic neuromyelitis after vaccination against SARS-CoV-2
Authors: Hernandez-Vega Melissa , Orozco-Narvaez Alejandro , Reyes-Vaca Jorge Guillermo , Rodriguez-Leyva Ildefonso
Published: December 2022

Neuromyelitis optica is an autoimmune demyelinating astrocytopathy of the central nervous system that primarily affects the optic nerve and spinal cord. It is considered a multifactorial disease associated with antibodies against aquaporin 4, with complement cascade activation and lymphocytic infiltration leading to axonal loss and causing significant morbidity and disability. In addition, cases of inflammatory diseases of the central nervous system have been described after vaccination against SARS-CoV-2, mainly acute disseminated encephalomyelitis. Also, a few cases of neuromyelitis optica spectrum disorder, mostly aquaporin 4+, have been reported. We describe a patient who developed symptoms suggestive of acute disseminated encephalomyelitis the next day after vaccination against SARS-CoV-2. Three months later, a longitudinally extensive transverse myelitis compatible with aquaporin 4+ neuromyelitis optica was successfully treated with an interleukin 6 inhibitor. There is no proven association and research is needed to establish whether optic neuromyelitis is related to vaccination; this is a single case report from which no conclusion can be drawn.
The matricellular protein CCN3 supports lung endothelial homeostasis and function
Authors: Betageri Kalpana R. , Link Patrick A. , Haak Andrew J. , Ligresti Giovanni , Tschumperlin Daniel J. , Caporarello Nunzia
Published: December 2022

Aberrant vascular remodeling contributes to the progression of many aging-associated diseases, including idiopathic pulmonary fibrosis (IPF), where heterogeneous capillary density, endothelial transcriptional alterations, and increased vascular permeability correlate with poor disease outcomes. Thus, identifying disease-driving mechanisms in the pulmonary vasculature may be a promising strategy to limit IPF progression. Here, we identified Ccn3 as an endothelial-derived factor that is upregulated in resolving but not in persistent lung fibrosis in mice, and whose function is critical for vascular homeostasis and repair. Loss and gain of function experiments were carried out to test the role of CCN3 in lung microvascular endothelial function in vitro through RNAi and the addition of recombinant human CCN3 protein, respectively. Endothelial migration, permeability, proliferation, and in vitro angiogenesis were tested in cultured human lung microvascular endothelial cells (ECs). Loss of CCN3 in lung ECs resulted in transcriptional alterations along with impaired wound-healing responses, in vitro angiogenesis, barrier integrity as well as an increased profibrotic activity through paracrine signals, whereas the addition of recombinant CCN3 augmented endothelial function. Altogether, our results demonstrate that the matricellular protein CCN3 plays an important role in lung endothelial function and could serve as a promising therapeutic target to facilitate vascular repair and promote lung fibrosis resolution.
Atorvastatin remodels lipid distribution between liver and adipose tissues through blocking lipoprotein efflux in fish
Authors: Li Rui-Xin , Chen Ling-Yun , Limbu Samwel M. , Yao Bing , Qian Yi-Fan , Zhou Wen-Hao , Chen Li-Qiao , Qiao Fang , Zhang Mei-Ling , Du Zhen-Yu , Luo Yuan
Published: December 2022

The regulation of cholesterol metabolism in fish is still unclear. Statins play important roles in promoting cholesterol metabolism development in mammals. However, studies on the role of statins in cholesterol metabolism in fish are currently limited. The present study evaluated the effects of statins on cholesterol metabolism in fish. Nile tilapia ( Oreochromis niloticus) were fed on control diets supplemented with three atorvastatin levels (0, 12, and 24 mg/kg diet, ATV0, ATV12, and ATV24, respectively) for 4 wk. Intriguingly, the results showed that both atorvastatin treatments increased hepatic cholesterol and triglyceride contents mainly through inhibiting bile acid synthesis and efflux, and compensatorily enhancing cholesterol synthesis in fish liver ( P < 0.05). Moreover, atorvastatin treatment significantly inhibited hepatic very-low-density lipoprotein (VLDL) assembly and thus decreased serum VLDL content ( P < 0.05). However, fish treated with atorvastatin significantly reduced cholesterol and triglycerides contents in adipose tissue ( P < 0.05). Further molecular analysis showed that atorvastatin treatment promoted cholesterol synthesis and lipogenesis pathways, but inhibited lipid catabolism and low-density lipoprotein (LDL) uptake in the adipose tissue of fish ( P < 0.05). In general, atorvastatin induced the remodeling of lipid distribution between liver and adipose tissues through blocking VLDL efflux from the liver to adipose tissue of fish. Our results provide a novel regulatory pattern of cholesterol metabolism response caused by atorvastatin in fish, which is distinct from mammals: cholesterol inhibition by atorvastatin activates hepatic cholesterol synthesis and inhibits its efflux to maintain cholesterol homeostasis, consequently reduces cholesterol storage in fish adipose tissue.
Solving Multispecies Lotka–Volterra Equations by the Daftardar-Gejji and Jafari Method
Authors: Batiha Belal , Ghanim Firas , Alayed O. , Hatamleh Ra’ed , Heilat Ahmed Salem , Zureigat Hamzeh , Bazighifan Omar
Published: December 2022

In this article, we apply the Daftardar-Gejji and Jafari method (DJM) to solve the multispecies Lotka–Volterra equation. A comparison between the DJM, differential transformation method (DTM), the variational iteration method (VIM), and Adomian decomposition method (ADM) shows that the DJM is a reliable and powerful method for solving nonlinear equations. The efficiency and applicability of this method are confirmed by considering some examples. The proposed procedure provides better results in comparison to some existing methods.
Long-Term Outcomes after Rotational Atherectomy for Calcified Chronic Total Occlusion versus Nonchronic Total Occlusion Coronary Lesions
Authors: Elbasha Karim , Mankerious Nader , Alawady Mohamed , Ibrahim Ghada , Abdullah Radwa , Abdel-Wahab Mohamed , Hemetsberger Rayyan , Toelg Ralph , Richardt Gert , Allali Abdelhakim
Published: December 2022

Background. The role of rotational atherectomy (RA) in contemporary percutaneous coronary intervention (PCI) is expanding to include certain chronic total occlusion (CTO) lesions. However, the long-term outcome of RA in CTOs is still unclear. Objective. To investigate in-hospital and long-term outcomes after RA for CTO compared to non-CTO calcified lesions. Moreover, this report evaluates the role of the elective RA approach in calcified CTOs. Methods and Results. This study enrolled 812 patients (869 lesions; CTO, n = 80 versus non-CTO, n = 789). The mean age of the study population was 73.1 ± 8.6 years, the baseline characteristics were comparable in both groups. Balloon-resistant CTO lesions represented the main indication for RA in CTO patients (61.2%). The mean J-CTO score was 2.42 ± 0.95. The angiographic success rate was lower in CTO patients (88.8% vs 94.9%; p = 0.022). In-hospital major adverse cardiac events (MACE) rate was comparable in both groups (CTO 8.8% vs 7.0% in non-CTO;p = 0.557). At two-year follow-up, a higher target lesion failure (TLF) was observed in CTO group (25.5% vs 15.1%, log rank p = 0.041), driven by higher cardiac mortality while the clinically driven target lesion revascularisation (TLR) was comparable between the study groups. Elective RA for CTO had a shorter procedural time and lower rate of dissection (7.5% vs 25%; p = 0.030) compared to bail-out RA with similar long-term outcomes. Conclusion. Compared to non-CTO, RA for CTO can be performed with a high procedural success rate and comparable in-hospital outcomes. Apart from higher cardiac mortality in the CTO group, the long-term outcomes are comparable in both groups. Elective RA is a feasible and beneficial approach to be used in CTO intervention.
IFT20 Confers Paclitaxel Resistance by Triggering β-arrestin-1 to Modulate ASK1 Signaling in Breast Cancer
Authors: Qiu Ni , Jin Huan , Cui Lulu , Zhan Yong-tao , Xia Hao-ming , Jiang Ming , Zhou Jie , Liang Hong-ling , Ao Xiang , He Zhi-min , Li Hong-sheng
Published: December 2022

System paclitaxel-based chemotherapy is the first-line treatment regimen of defense against breast cancer, but inherent or acquired chemotherapy resistance remains a major obstacle in breast cancer therapy. Elucidating the molecular mechanism of chemoresistance is essential to improve the outcome of patients with breast cancer. Here, we demonstrate that intraflagellar transport 20 (IFT20) is positively associated with shorter relapse-free survival in patients with system paclitaxel-based chemotherapy. High-expressed IFT20 in breast cancer cells increases resistance to cell death upon paclitaxel treatment; in contrast, IFT20 knockdown enhances apoptosis in breast cancer cells in response to paclitaxel. Mechanistically, IFT20 triggers β-arrestin-1 to bind with apoptosis signal-regulating kinase 1 (ASK1) and promotes the ubiquitination of ASK1 degradation, leading to attenuating ASK1 signaling and its downstream JNK cascades, which helps cells to escape from cell death during paclitaxel treatment. Our results reveal that IFT20 drives paclitaxel resistance through modulating ASK1 signaling and identifies IFT20 as a potential molecular biomarker for predicting the response to paclitaxel therapeutic in breast cancer.

Implications:

IFT20 drives paclitaxel resistance through modulating ASK1 signaling and IFT20 may act as a potential molecular biomarker for predicting the response to paclitaxel therapeutic in breast cancer.
Targeting ULK1 Decreases IFNγ-Mediated Resistance to Immune Checkpoint Inhibitors
Authors: Fenton Sarah E. , Zannikou Markella , Ilut Liliana , Fischietti Mariafausta , Ji Chunni , Oku Chidera V. , Horvath Curt M. , Le Poole I. Caroline , Bosenberg Marcus , Bartom Elizabeth T. , Kocherginsky Masha , Platanias Leonidas C. , Saleiro Diana
Published: December 2022

Immune checkpoint inhibitors (ICI) have transformed the treatment of melanoma. However, the majority of patients have primary or acquired resistance to ICIs, limiting durable responses and patient survival. IFNγ signaling and the expression of IFNγ-stimulated genes correlate with either response or resistance to ICIs, in a context-dependent manner. While IFNγ-inducible immunostimulatory genes are required for response to ICIs, chronic IFNγ signaling induces the expression of immunosuppressive genes, promoting resistance to these therapies. Here, we show that high levels of Unc-51 like kinase 1 (ULK1) correlate with poor survival in patients with melanoma and overexpression of ULK1 in melanoma cells enhances IFNγ-induced expression of immunosuppressive genes, with minimal effects on the expression of immunostimulatory genes. In contrast, genetic or pharmacologic inhibition of ULK1 reduces expression of IFNγ-induced immunosuppressive genes. ULK1 binds IRF1 in the nuclear compartment of melanoma cells, controlling its binding to the programmed death-ligand 1 promoter region. In addition, pharmacologic inhibition of ULK1 in combination with anti-programmed cell death protein 1 therapy further reduces melanoma tumor growth in vivo. Our data suggest that targeting ULK1 represses IFNγ-dependent immunosuppression. These findings support the combination of ULK1 drug-targeted inhibition with ICIs for the treatment of patients with melanoma to improve response rates and patient outcomes.

Implications:

This study identifies ULK1, activated downstream of IFNγ signaling, as a druggable target to overcome resistance mechanisms to ICI therapy in metastatic melanoma.
Infiltration of Tumors Is Regulated by T cell–Intrinsic Nitric Oxide Synthesis
Authors: Cunha Pedro P. , Bargiela David , Minogue Eleanor , Krause Lena C.M. , Barbieri Laura , Brombach Carolin , Gojkovic Milos , Marklund Emilia , Pietsch Sandra , Foskolou Iosifina , Branco Cristina M. , Veliça Pedro , Johnson Randall S.
Published: December 2022

Nitric oxide (NO) is a signaling molecule produced by NO synthases (NOS1–3) to control processes such as neurotransmission, vascular permeability, and immune function. Although myeloid cell–derived NO has been shown to suppress T-cell responses, the role of NO synthesis in T cells themselves is not well understood. Here, we showed that significant amounts of NO were synthesized in human and murine CD8+ T cells following activation. Tumor growth was significantly accelerated in a T cell–specific, Nos2-null mouse model. Genetic deletion of Nos2 expression in murine T cells altered effector differentiation, reduced tumor infiltration, and inhibited recall responses and adoptive cell transfer function. These data show that endogenous NO production plays a critical role in T cell–mediated tumor immunity.
Infectious Keratitis in Corneal Graft following Astigmatic Keratotomy: A Case Report and Literature Review
Authors: AlKharashi Majed , Otaif Wael , Al-Essa Rakan S.
Published: December 2022

Femtosecond laser-assisted astigmatic keratotomy (FSAK) is recognized as a safe and effective therapeutic option for addressing high corneal astigmatism in corneal transplants. Although the incidence of corneal infection after FSAK in corneal transplants is very low, early detection and treatment is necessary to optimize visual outcomes and prevent devastating sequelae. This report describes a rare case of an early-onset infectious keratitis occurring in a corneal transplant after FSAK. A 38-year-old man with previous history of penetrating keratoplasty and FSAK presented to emergency department with deep corneal infiltration at the FASK incision site along with a decline in his baseline best corrected visual acuity 1 month after FSAK. Corneal scraping was performed, and topical fortified antibiotic eyedrops were started. Culture results showed no growth. Three weeks later, the corneal infiltrate resolved with residual scarring at the FSAK incision site, and the patient regained his baseline best corrected visual acuity with no sequelae.
COVID-19: Ventilatorassoziierte Pneumonien und multiresistente Erreger bei beatmeten Patienten
Authors: Knoch Johannes
Published: December 2022

Background: COVID-19 is a novel cause of acute respiratory distress syndrome (ARDS) that leads patients to intensive care unit (ICU) admission requiring invasive ventilation, who consequently are at risk of developing of ventilator-associated pneumonia (VAP). The aim of this study was to assess the incidence, antimicrobial resistance, risk factors, and outcome of VAP in ICU COVID-19 patients in invasive mechanical ventilation (MV). Methods: Observational prospective study including adult ICU admissions between January 1, 2021, and June 31, 2021, with confirmed COVID-19 diagnosis were recorded daily, including demographics, medical history, ICU clinical data, etiology of VAPs, and the outcome. The diagnosis of VAP was based on multi-criteria decision analysis which included a combination of radiological, clinical, and microbiological criteria in ICU patients in MV for at least 48 h. Results: Two hundred eighty-four COVID-19 patients in MV were admitted in ICU. Ninety-four patients (33%) had VAP during the ICU stay, of which 85 had a single episode of VAP and 9 multiple episodes. The median time of onset of VAP from intubation were 8 days (IQR, 5–13). The overall incidence of VAP was of 13.48 episodes per 1000 days in MV. The main etiological agent was Pseudomonas aeruginosa (39.8% of all VAPs) followed by Klebsiella spp. (16.5%); of them, 41.4% and 17.6% were carbapenem resistant, respectively. Patients during the mechanical ventilation in orotracheal intubation (OTI) had a higher incidence than those in tracheostomy, 16.46 and 9.8 episodes per 1000-MV day, respectively. An increased risk of VAP was reported in patients receiving blood transfusion (OR 2.13, 95% CI 1.26–3.59, p = 0.005) or therapy with Tocilizumab/Sarilumab (OR 2.08, 95% CI 1.12–3.84, p = 0.02). The pronation and PaO2/FiO2 ratio at ICU admission were not significantly associated with the development of VAPs. Furthermore, VAP episodes did not increase the risk of death in ICU COVID-19 patients. Conclusions: COVID-19 patients have a higher incidence of VAP compared to the general ICU population, but it is similar to that of ICU ARDS patients in the pre-COVID-19 period. Interleukin-6 inhibitors and blood transfusions may increase the risk of VAP. The widespread use of empirical antibiotics in these patients should be avoided to reduce the selecting pressure on the growth of multidrug-resistant bacteria by implementing infection control measures and antimicrobial stewardship programs even before ICU admission.
Serum Sclerostin Levels and Mortality in Hemodialysis Patients: An 8-Year Prospective Study
Authors: Nakagawa Yosuke , Komaba Hirotaka , Wada Takehiko , Takahashi Hiroo , Takahashi Yuichiro , Hyodo Toru , Hida Miho , Suga Takao , Kakuta Takatoshi , Fukagawa Masafumi
Published: December 2022

Introduction: Sclerostin is an osteocyte-derived inhibitor of bone formation and is increased in kidney failure. Sclerostin might be involved in the pathogenesis of vascular calcification, but few studies have examined the association between sclerostin and mortality in hemodialysis patients. Methods: We analyzed a prospective cohort of 654 patients undergoing maintenance hemodialysis. The primary exposure variable was the baseline serum sclerostin level measured at study enrollment. The primary outcome was 8-year all-cause mortality. Mortality risk was assessed using Cox regression models adjusted for potential confounders. Results: During a median follow-up of 7.6 years (interquartile range, 4.1–8.0 years), 229 of the 654 participants died. In a univariate analysis, serum sclerostin levels were not associated with mortality (HR per doubling, 0.94; 95% CI, 0.76–1.17). This result was unchanged after adjustment for age, sex, dialysis vintage, diabetes, prior cardiovascular disease, and body mass index (HR per doubling, 0.92; 95% CI, 0.72–1.17). Similar results were obtained for cardiovascular mortality. Conclusion: Serum sclerostin levels were not associated with mortality in maintenance hemodialysis patients. Further research is required to determine the role of sclerostin in vascular calcification and cardiovascular disease in kidney failure.
The Mediating Role of Work Engagement in the Effect of Leader-Member Exchange on Job Performance
Authors: ÖZBEZEK B. Dilek , EGE Tayfur
Published: December 2022

Today, in order for businesses to sustain their presence and gain a competitive advantage in the sector in which they operate, their employees must be able to achieve a high level of performance consistently. Although there are many factors affecting job performance, a leader-member exchange is an important concept used to explain the relationship between manager and employee. This study aims to determine to what extent leader-member exchange affects job performance levels and to determine the mediating role of work engagement in this interaction. The research population of this study consists of business employees operating in the textile sector in Gaziantep 5th Organized Industrial Region. The sample size reached for this study is 284 participants. The data obtained from the participants by the face-to-face survey was tested by performing explanatory and confirmatory factor analysis, descriptive statistics, correlation, and bootstrap regression analysis. The results of conceptual and empirical studies clearly show that there is a statistically significant relation between leader-member exchange and job performance. However, work engagement has a partial mediating role in the relation between job performance and leader-member exchange.
Unequal outcomes: The effects of the COVID-19 pandemic on mental health and wellbeing among Hispanic/Latinos with varying degrees of ‘Belonging’
Authors: Baxter Tatiana , Shenoy Sunil , Lee Hyeon-Seung , Griffith Taylor , Rivas-Baxter Angelica , Park Sohee
Published: December 2022

Background:

The COVID-19 pandemic has brought disparities in mental and physical health faced by ethnic minorities to the forefront. In the U.S., Hispanic/Latino communities are plagued by elevated rates of psychiatric conditions and trauma. Exacerbating this burden, common discourse often implicates Hispanic/Latino ethnicity as a causal factor, despite clear evidence of systemic causes, including lack of access to resources, and discrimination.

Aims:

To parse apart Hispanic/Latino ethnicity from determinants of wellbeing (such as trauma, financial status, and loneliness), we examined mental and physical health during COVID-19 via an online, anonymous survey available in both English and Spanish.

Methods:

We examined wellbeing across three participant groups, including two groups of Hispanic/Latino adults with varying degrees of ‘belonging’ to the dominant culture in their country of residence: Hispanic/Latino individuals living in Spanish-speaking and/or Central or Latin American countries (Group 1), Hispanic/Latino individuals living in the U.S. (Group 2), and non-Hispanic/Latino individuals living in the U.S. (Group 3).

Results:

Results demonstrated there were significant differences between groups in specific aspects of wellbeing. Most importantly, results showed Hispanic/Latino ethnicity does not significantly predict psychosocial wellbeing or psychosis risk, and identified several predictors of these outcomes, including U.S. residence, trauma, loneliness, and age.

Conclusion:

Our results demonstrate that Hispanic/Latino ethnicity itself is not a causal factor of poor psychosocial wellbeing or elevated psychosis risk and instead identify several social and systemic causal factors commonly faced by Hispanic/Latino Americans. We suggest that language reporting on minority mental health acknowledge systemic factors as contributing to poor outcome rather than referring to ethnicity as if it were a causal factor.
Age, Gender and One’s Perception of Discrimination Against Men Versus Women in Korea
Authors: Lee Yeon Jung , Na Jinkyung , Kim Bo Kyung
Published: December 2022

The present research investigated whether and (if so) how one’s perception of gender discrimination would vary as a function of age and gender in Korea. Since gender-related conflicts have escalated in Korea especially among younger adults, we predicted that (1) there would be gender differences in one’s perception of gender discrimination in Korea and (2) such differences would be particularly large among younger adults. Consistent with the predictions, we found that Korean men underestimated discrimination against women and overestimated discrimination against men, relative to Korean women. Also, such tendency was more pronounced among younger men than among older men without significant differences in sexism between them. Moreover, young men claimed that men were at least as discriminated against as women in Korea unlike other groups who believed that discrimination against women was larger than discrimination against men. Our data also suggest that such perception of gender discrimination among younger Korean men is possibly due to their beliefs that social atmosphere in Korea is disadvantageous to their gender. We further showed that gender differences in perception of gender discrimination were associated with corresponding differences in emotional reactions (i.e., anger) to gender discrimination.
Economic Value of Tourism Through Human Capital Gains
Authors: Buckley Ralf
Published: December 2022

Leisure tourism can be analyzed as a mechanism to rebuild human capital depleted by work. Human capital is an essential input to human economies, and possesses a corresponding economic value. Therefore, tourism possesses an economic value additional to expenditure and multipliers, which can be seen as investments in increasing human capital as an asset. Calculating the financial value of human capital gains is likely to prove a more powerful political tool for the tourism sector, than current political perceptions as discretionary leisure.
Juneau, Alaska’s Successful Response to COVID-19: A Case Study of Adaptive Leadership in a Complex System
Authors: Powell James E. , Orttung Robert W. , Topkok Sean Asikłuk , Akselrod Hana , Little Joseph , Wilcox Peggy
Published: December 2022

Juneau, Alaska, kept COVID-19 deaths lower than in other similar jurisdictions. We argue that adaptive leadership—the early decisions and actions of Juneau’s leaders, effective communications, and emergent new collaborative structures—in the context of municipal ownership of key assets enabled Juneau’s success. The result of 61 interviews and follow-up research, this case study contributes a better understanding of which institutional design, communication, and collaborative factors mattered in responding to the pandemic. Adaptive leadership provides a better explanation for Juneau’s success than alternatives that focus on its isolation, home-rule status, and socio-economic structure.
In Silico Prediction of Human Clinical Pharmacokinetics with ANDROMEDA by Prosilico: Predictions for an Established Benchmarking Data Set, a Modern Small Drug Data Set, and a Comparison with Laboratory Methods
Authors: Fagerholm Urban , Hellberg Sven , Alvarsson Jonathan , Spjuth Ola
Published: December 2022

There is an ongoing aim to replace animal and in vitro laboratory models with in silico methods. Such replacement requires the successful validation and comparably good performance of the alternative methods. We have developed an in silico prediction system for human clinical pharmacokinetics, based on machine learning, conformal prediction and a new physiologically-based pharmacokinetic model, i.e. ANDROMEDA. The objectives of this study were: a) to evaluate how well ANDROMEDA predicts the human clinical pharmacokinetics of a previously proposed benchmarking data set comprising 24 physicochemically diverse drugs and 28 small drug molecules new to the market in 2021; b) to compare its predictive performance with that of laboratory methods; and c) to investigate and describe the pharmacokinetic characteristics of the modern drugs. Median and maximum prediction errors for the selected major parameters were ca 1.2 to 2.5-fold and 16-fold for both data sets, respectively. Prediction accuracy was on par with, or better than, the best laboratory-based prediction methods (superior performance for a vast majority of the comparisons), and the prediction range was considerably broader. The modern drugs have higher average molecular weight than those in the benchmarking set from 15 years earlier ( ca 200 g/mol higher), and were predicted to (generally) have relatively complex pharmacokinetics, including permeability and dissolution limitations and significant renal, biliary and/or gut-wall elimination. In conclusion, the results were overall better than those obtained with laboratory methods, and thus serve to further validate the ANDROMEDA in silico system for the prediction of human clinical pharmacokinetics of modern and physicochemically diverse drugs.