bluuebunny/crossref_metadata_2025 huggingface dataset:
A DSM-5 AMPD and ICD-11 compatible measure for an early identification of personality disorders in adolescence – LoPF-Q 12-18 latent structure and short form
Authors: Zimmermann Ronan , Steppan Martin , Zimmermann Johannes , Oeltjen Lara , Birkhölzer Marc , Schmeck Klaus , Goth Kirstin
Published: May 2022

The LoPF-Q 12-18 (Levels of Personality Functioning Questionnaire) was designed for clinical use and to promote early detection of personality disorder (PD). It is a self-report measure with 97 items to assess personality functioning in adolescents from 12 years up. It operationalizes the dimensional concept of personality disorder (PD) severity used in the Alternative DSM-5 Model for Personality Disorders and the ICD-11. In this study, we investigated the factorial structure of the LoPF-Q 12-18. Additionally, a short version was developed to meet the need of efficient screening for PD in clinical and research applications.

To investigate the factorial structure, several confirmatory factor analysis models were compared. A bifactor model with a strong general factor and four specific factors showed the best nominal fit (CFI = .91, RMSEA = .04, SRMR = .07).

The short version was derived using the ant colony optimization algorithm. This procedure resulted in a 20-item version with excellent fit for a hierarchical model with four first order factors to represent the domains and a secondary higher order factor to represent personality functioning (CFI = .98, RMSEA = .05, SRMR = .04). Clinical validity (effect size d= 3.1 between PD patients and controls) and clinical utility (cutoff ≥ 36 providing 87.5% specificity and 80.2% sensitivity) for detecting patients with PD were high for the short version. Both, the long and short LoPF-Q 12-18 version are ready to be used for research and diagnostic purposes.
A single closed head injury in mice induces chronic, progressive white matter atrophy and increased phospho-tau expressing oligodendrocytes
Authors: Havlicek David F. , Furhang Rachel , Nikulina Elena , Smith-Salzberg Bayle , Lawless Siobhán , Sevarin Sasha A. , Mallaboeva Sevara , Nayab Fizza , Seifert Alan C. , Crary John F. , Bergold Peter J.
Published: May 2022

Traumatic brain injury (TBI) acutely damages the brain; this injury can evolve into chronic neurodegeneration. While much is known about the chronic effects arising from multiple mild TBIs, far less is known about the long-term effects of a single moderate to severe TBI. We found that a single moderate closed head injury to mice induces diffuse axonal injury within 1-day post-injury (DPI). At 14 DPI, injured animals have atrophy of ipsilesional cortex, thalamus, and corpus callosum, with bilateral atrophy of the dorsal fornix. Atrophy of the ipsilesional corpus callosum is accompanied by decreased fractional anisotropy and increased mean and radial diffusivity that remains unchanged between 14 and 180 DPI. Injured animals increased density of phospho-tau immunoreactive (pTau+) cells in the ipsilesional cortex and thalamus, and bilaterally in corpus callosum. Between 14 and 180 DPI, atrophy occurs in the ipsilesional ventral fornix, contralesional corpus callosum, and bilateral internal capsule. Diffusion tensor MRI parameters remain unchanged in white matter regions with delayed atrophy. Between 14 and 180 DPI, pTau+cell density increases bilaterally in corpus callosum, but decreases in cortex and thalamus. The location of pTau+cells within the ipsilesional corpus callosum changes between 14 and 180 DPI; density of all cells increases including pTau+or pTau-cells. Greater than 90% of the pTau+cells are in the oligodendrocyte lineage in both gray and white matter. Density of thioflavin-S+cells in thalamus increases by 180 DPI. These data suggest a single closed head impact produces multiple forms of chronic neurodegeneration. Gray and white matter regions proximal to the impact site undergo rapid atrophy. More distal white matter regions undergo chronic, progressive white matter atrophy with an increasing density of oligodendrocytes containing pTau. These data suggest that the chronic neurodegeneration arising from a single moderate CHI differs greatly from the chronic traumatic encephalopathy produced by multiple mild head injuries.

Highlights

Gray and white matter atrophy begins within 14 days after a single closed head injury

White matter atrophy progresses between 14 and 180 days post injury with minimal changes in diffusion tensor MRI parameters.

CHI increases the density of oligodendrocytes with perinuclear accumulation of phosphorylated tau

Thioflavin-S+cells increase in thalamus at 180 days post injury
Periostin+stromal cells guide lymphovascular invasion by cancer cells
Authors: Null Jamie L. , Kim Dae Joong , McCann James V. , Pramoonjago Patcharin , Fox Jay W. , Kumar Pankaj , Edatt Lincy , Pecot Chad V. , Dudley Andrew C.
Published: May 2022

Cancer cell dissemination to the sentinel lymph node associates with poor patient outcomes, particularly in breast cancers. How cancer cells egress the primary tumor upon interfacing with the lymphatic vasculature is complex and driven by dynamic interactions between cancer cells and stromal cells including cancer associated fibroblasts (CAFs). The matricellular protein periostin can distinguish CAF subtypes in breast cancer and is associated with increased desmoplasia and disease recurrence in patients. However, since periostin is secreted, periostin-expressing CAFs are difficult to characterize in situ, limiting our understanding of their specific contribution to cancer progression. Here, we used in vivo genetic labelling and ablation to lineage trace periostin+cells and characterize their function(s) during tumor growth and metastasis. We report that periostin-expressing CAFs are spatially found at periductal and perivascular margins, are enriched at lymphatic vessel peripheries, and are differentially activated by highly-metastatic cancer cells versus low-metastatic counterparts. Surprisingly, genetically depleting periostin+CAFs slightly accelerated primary tumor growth but impaired intratumoral collagen organization and inhibited lymphatic, but not lung, metastases. Periostin ablation in CAFs impaired their ability to deposit aligned collagen matrices and inhibited cancer cell invasion through collagen and across lymphatic endothelial cell monolayers. Thus, highly-metastatic cancer cells mobilize periostin-expressing CAFs in the primary tumor site which promote collagen remodeling and collective cell invasion within lymphatic vessels and ultimately to sentinel lymph nodes.

Significance Statement

Metastatic disease causes the majority of cancer-related deaths but is challenging to treat as it is a complex multi-step process driven by heterotypic cell interactions. Cancer-associated fibroblasts (CAFs) are abundant in most solid tumors and display pro-tumorigenic and pro-metastatic functions, but extensive molecular diversity among CAFs has yielded contradictory results in previous attempts to target this population. Therefore, there is a need to identify markers of CAF subpopulations that promote or inhibit metastasis and functionally characterize them to understand their contributions during tumor progression. Our work identifies a population of CAFs, marked by expression of the matricellular protein periostin, that remodel the ECM to promote the escape of cancer cells into lymphatic vessels thereby driving colonization of proximal lymph nodes.
Epigenetic Age and Lung Cancer Risk in the CLUE II Prospective Cohort Study
Authors: Michaud Dominique S. , Chung Mei , Zhao Naisi , Koestler Devin C. , Lu Jiayun , Platz Elizabeth A. , Kelsey Karl T.
Published: May 2022

Background

Epigenetic age, a robust marker of biological aging, has been associated with obesity, low-grade inflammation and metabolic diseases. However, few studies have examined associations between different epigenetic age measures and risk of lung cancer, despite great interest in finding biomarkers to assist in risk stratification for lung cancer screening.

Methods

A nested case-control study of lung cancer from the CLUE II cohort study was conducted using incidence density sampling with 1:1 matching of controls to lung cancer cases (n=208 matched pairs). Prediagnostic blood samples were collected in 1989 (CLUE II study baseline) and stored at −70°C. DNA was extracted from buffy coat and DNA methylation levels were measured using Illumina MethylationEPIC BeadChip Arrays. Three epigenetic age acceleration (i.e., biological age is greater than chronological age) measurements (Horvath, Hannum and PhenoAge) were examined in relation to lung cancer risk using conditional logistic regression.

Results

We did not observe associations between the three epigenetic age acceleration measurements and risk of lung cancer overall; however, inverse associations for the two Hannum age acceleration measures (intrinsic and extrinsic) were observed in men and among younger participants, but not in women or older participants. We did not observe effect modification by time from blood draw to diagnosis.

Conclusion

Findings from this study do not support a positive association between three different biological age acceleration measures and risk of lung cancer. Additional studies are needed to address whether epigenetic age is associated with lung cancer in never smokers.
Omicron and vaccines: An analysis on the decline in COVID-19 mortality
Authors: Larrauri Blas J. , Malbrán Alejandro , Larrauri José A.
Published: May 2022

The SARS-CoV-2 virus emerged in December 2019 infecting more than 430 million people worldwide and causing almost 6 million deaths until February 2022. Rapid vaccination efforts during this period coincided with a reduction in the mortality rate of the virus. A new genetic COVID-19 variant named Omicron appeared and widely spread by the end of 2021, after which the COVID-19 mortality rate showed a marked, albeit temporary, decline. The potential relationship between vaccines and omicron infection on the mortality rate of COVID-19 is analyzed in this article using online data from public sources from countries with relatively high incidence of infection. Mortality and incidence rates were compared before and after Omicron became the prevalent source of COVID-19 cases, as well as the effect of vaccination during these periods. Infection rates were higher during Omicron than in the pre-Omicron period (4.16% vs. 2%, respectively), whereas mortality rates showed the opposite trend both in deaths over population (0.021% vs. 0.171%) and deaths over positive cases (0.27% vs. 1.07%, respectively). The results suggest that vaccines, while significantly reducing mortality, did not prevent Omicron infection; and that during the Omicron period mortality decreased by a low aggressiveness of this variant.

Key Messages

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Vaccines do not appear to have prevented Omicron infection.

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Infection rates were higher during the Omicron period than before it.

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Mortality rates were lower during the Omicron period than before it.

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Vaccines reduced mortality rates during both pre- and Omicron periods.

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The sharp decrease in mortality rates during the Omicron period seems to be due to the low virulence of Omicron strains rather than vaccine efficacy.
Epigenetic plasticity via adaptive DNA hypermethylation and clonal expansion underlie resistance to oncogenic pathway inhibition in pancreatic cancer
Authors: Godfrey Laura K. , Forster Jan , Liffers Sven-Thorsten , Schröder Christopher , Köster Johannes , Henschel Leonie , Ludwig Kerstin U. , Trajkovic-Arsic Marija , Behrens Diana , Scarpa Aldo , Lawlor Rita T. , Witzke Kathrin E. , Sitek Barbara , Johnsen Steven A. , Rahmann Sven , Horsthemke Bernhard , Zeschnigk Michael , Siveke Jens T.
Published: May 2022

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with poor prognosis. Drug resistance is the major cause for therapeutic failure in PDAC patients with progressive disease. The mechanisms underlying resistance formation are complex and remain poorly understood.

To gain insights into molecular changes during the formation of resistance to oncogenic MAPK pathway inhibition we utilized short-term passaged primary tumor cells from ten PDACs of genetically engineered mice. We followed gain and loss of resistance upon MEKiexposure and withdrawal by longitudinal integrative analysis of whole genome sequencing, whole genome bisulfite sequencing, RNA-sequencing and mass spectrometry data.

We found that resistant cell populations under increasing MEKitreatment evolved by the expansion of a single clone but were not a direct consequence of known resistance-conferring mutations. Rather, resistant cells showed adaptive DNA hypermethylation of 209 and hypomethylation of 8 genomic sites, most of which overlap with regulatory elements known to be active in murine PDAC cells. Both DNA methylation changes and MEKiresistance were transient and reversible upon drug withdrawal. The effector caspaseCASP3is one of the 114 genes for which transcriptional downregulation inversely correlated with the methylation status of the associated DNA region. CASP3 inactivation in resistant cells led to attenuation of drug-induced apoptosis which could be reversed by DNA methyltransferase inhibition with remarkable sensitivity exclusively in the resistant cells.

Overall, our data provide a context for characterization and targeting of epigenetically mediated resistance mechanisms in PDAC.
Scientific hypothesis generation process in clinical research: a secondary data analytic tool versus experience study protocol
Authors: Jing Xia , Patel Vimla L. , Cimino James J. , Shubrook Jay H. , Zhou Yuchun , Liu Chang , De Lacalle Sonsoles
Published: May 2022

Background

Scientific hypothesis generation is a critical step in scientific research that determines the direction and impact of any investigation. Despite its vital role, we have limited knowledge of the process itself, hindering our ability to address some critical questions.

Objective

To what extent can secondary data analytic tools facilitate scientific hypothesis generation during clinical research? Are the processes similar in developing clinical diagnoses during clinical practice and developing scientific hypotheses for clinical research projects? We explore the process of scientific hypothesis generation in the context of clinical research. The study is designed to compare the role of VIADS, our web-based interactive secondary data analysis tool, and the experience levels of study participants during their scientific hypothesis generation processes.

Methods

Inexperienced and experienced clinical researchers are recruited. In this 2×2 study design, all participants use the same data sets during scientific hypothesis-generation sessions, following pre-determined scripts. The inexperienced and experienced clinical researchers are randomly assigned into groups with and without using VIADS. The study sessions, screen activities, and audio recordings of participants are captured. Participants use the think-aloud protocol during the study sessions. After each study session, every participant is given a follow-up survey, with participants using VIADS completing an additional modified System Usability Scale (SUS) survey. A panel of clinical research experts will assess the scientific hypotheses generated based on pre-developed metrics. All data will be anonymized, transcribed, aggregated, and analyzed.

Results

This study is currently underway. Recruitment is ongoing via a brief online survey 1. The preliminary results show that study participants can generate a few to over a dozen scientific hypotheses during a 2-hour study session, regardless of whether they use VIADS or other analytic tools. A metric to assess scientific hypotheses within a clinical research context more accurately, comprehensively, and consistently has also been developed.

Conclusion

The scientific hypothesis-generation process is an advanced cognitive activity and a complex process. Clinical researchers can quickly generate initial scientific hypotheses based on data sets and prior experience based on our current results. However, refining these scientific hypotheses is much more time-consuming. To uncover the fundamental mechanisms of generating scientific hypotheses, we need breakthroughs that capture thinking processes more precisely.
Shared genetic etiology and causality between COVID-19 and venous thromboembolism: evidence from genome-wide cross trait analysis and bi-directional Mendelian randomization study
Authors: Huang Xin , Yao Minhao , Tian Peixin , Wong Jason Y.Y. , Li Zilin , Liu Zhonghua , Zhao Jie V.
Published: May 2022

Venous thromboembolism (VTE) occurs in up to one third patients with COVID-19. VTE and COVID-19 may share a common genetic architecture, which has not been clarified yet. To fill this gap, we leveraged summary-level genetic data from the latest COVID-19 host genetics consortium and UK Biobank and examined the shared genetic etiology and causal relationship between COVID-19 and VTE. The cross-trait analysis identified 8, 11, and 7 shared loci between VTE and severe COVID-19, COVID-19 hospitalization, SARS-CoV-2 infection respectively, in 13 genes involved in coagulation and immune function and enriched in the lung. Co-localization analysis identified eight shared loci in ABO, ADAMTS13 and FUT2 genes. Bi-direction Mendelian randomization suggested that VTE was associated with higher risks of all COVID-19 related traits, and SARS-CoV-2 infection was associated with higher risk of VTE. Our study provided timely evidence and novel insights into the genetic etiology between COVID-19 and VTE.
Somatic hypermutation patterns in immunoglobulin variable regions are established independently of the local transcriptional landscape
Authors: Schoeberl Ursula E. , Fitz Johanna , Froussios Kimon , Valieris Renan , Ourailidis Iordanis , Makharova Marina , Bauer Bernd , Neumann Tobias , Wiedemann Eva-Maria , Steininger Monika , Garcia Adriana Cantoran , Mastrovito Marialaura , Mouquet Hugo , Da Silva Israel Tojal , Pavri Rushad
Published: May 2022

Somatic hypermutation (SHM) of immunoglobulin variable (V) regions modulates antibody-antigen affinity is initiated by activation-induced cytidine deaminase (AID) on single-stranded DNA (ssDNA). Transcription is essential for SHM and AID target genes harbor activating chromatin marks and RNA polymerase II (Pol II) stalling, leading to the model that these features favor higher rates of mutagenesis. However, whether such relationships exist within V regions is undetermined. Here, we directly compared SHM and nascent transcription across four V regions and 275 non-immunoglobulin SHM targets at single-nucleotide resolution using precision run-on sequencing (PRO-seq). Although locales of Pol II enrichment and zones of Pol II stalling were detected within V regions, their correlation with SHM was not statistically significant. Moreover, SHM was robust against major reductions of activating epigenetic marks and transcription. This data suggests that SHM patterns and spectra are established independently of specific local nascent transcriptional features.
The Survival Analysis of Veterans’ Administration Lung Cancer Dataset
Authors: Amaka Ewuru Deborah , Etikan İlker
Published: May 2022

AIM

This study will describe the notion about survival analysis and the variability between diverse methods and test statistics used in analyzing survival data.

METHODS

This study will be using the Veterans’ Administrative Lung Cancer dataset(R Dataset) of 137 patients having advanced inoperable Lung cancer, carried out by the US Veterans Administration. Out of 137 male patients, 69 patients received the Standard test while 68 patients received Chemotherapy test and 64 patients died in each treatment group while only 9 patients were alive (censored) at the end of the study. This dataset will be analyzed using the SPSS version to determine whether there is a statistically remarkable difference between the survival distributions of the cell types of Lung cancer using Life tables, and also between the Standard test and Chemotherapy test treatment groups using Kaplan Meier method. Various covariates were also analyzed to find out if they have any effect on the death of the male patients with advanced inoperable lung cancer using Cox-Regression.

RESULTS

The Wilcoxon (Gehan) statistic from Life table method shows a p-value of 0.000 less than the 95% confidence level indicating that there is a statistical significance between the Lung cancer cell types. The three statistical tests of Kaplan-Meier method which include Log Rank (Mantel-Cox) test, Breslow (Generalized Wilcoxon) and Tarone Ware tests showed that the survival distribution between the two Lung cancer treatment groups are equal using an alpha level of 0.05.The Standard test and the Chemotherapy test drug treatment show the same effect on the survival time of the patients, no treatment is more beneficial than the other. Cox Regression result showed that Squamous cell type2(4), Adeno-carcinoma cell type (1), Small cell type (3) and karnofsky score are statistically significant while Large cell type2 (2), prior therapy, age, diagnosis time and the treatment group were found not significant.

CONCLUSION

The treatment difference does not show any remarkable effect on the survival time of male patients with Lung Cancer.
Male mate preference against tail-elongated females in the barn swallow
Authors: Hasegawa Masaru , Arai Emi
Published: May 2022

The function of female ornamentation in the context of (inter)sexual selection attracts keen attention these days, but empirical field studies are mostly based on indirect measures such as mating patterns; direct evidence of male mate preference on female ornamentation while controlling for confounding factors is needed. Here we performed model presentation experiments to study male mate preference in the barn swallowHirundo rustica, a model species of sexual selection. Female barn swallows have somewhat shorter tails than males, but their tails are still long and costly. Although many correlational and experimental studies of live females have focused on long tails in female barn swallows over the last three decades, direct behavioral tests of male mate preference are lacking. By using a sequential model presentation experiment, in which we repeated the trials with the same males, we found that males significantly reduced the number of pairing displays when they were presented with tail-elongated female models compared to control female models. Interaction between treatment and male tail length was far from significant. The observed pattern is inconsistent with the prevailing view that costly female ornamentation is maintained via male preference for more ornamented females. Rather, the observed pattern is consistent with the sexual mimicry hypothesis, in which females can avoid sexual (and social) harassment by mimicking males.
The 5-Hydroxytryptaminergic Neurons in the Dorsal Raphe Nucleus and Different 5-HT Receptors are Implicated in Mediating the Awakening from Sevoflurane Anesthesia
Authors: Ma HaiXiang , Gu LeYuan , Wang YuLing , Xu Qing , Yu Qian , Lian XiTing , Shao WeiHui , Liu Lu , Gu JiaXuan , Shen Yue , Zhang HongHai
Published: May 2022

In order to explore the mechanism of general anesthesia emergence, based on the common clinical phenomenon-delayed emergence, we explore the role of 5-hydroxytryptamine (5-HT) neurons in the dorsal raphe nucleus in promoting awakening from sevoflurane anesthesia in mice model. In this study, C57BL/6J male mice were selected to specifically activate or inhibit 5-HT neurons in the dorsal raphe nucleus (DRN) and different 5-HT receptors by intraperitoneal, lateral ventricle, intranuclear or DRN injection of agonists/antagonists and optogenetics during the sevoflurane anesthesia to record and observe the anesthesia induction and emergence time of mice. Through intraventricular infusion and intranuclear microinjection of 5-HT and the agonists or antagonists of different 5-HT receptors, our data showed that 5-HT and 5-HT1A and 2A/C receptors, especially 5-HT1A receptor, are involved in the regulation of delayed awakening mediated by DRN 5-HT neurons. This can provide a reliable theoretical basis as well as potential targets for clinical intervention to prevent delayed emergence and some postoperative risks.

Graphical Abstract
Single-Cell Transcriptome Analyses Reveal the Cell Diversity and Developmental Features of Human Gastric and Metaplastic Mucosa
Authors: Tsubosaka Ayumu , Komura Daisuke , Katoh Hiroto , Kakiuchi Miwako , Onoyama Takumi , Yamamoto Asami , Abe Hiroyuki , Seto Yasuyuki , Ushiku Tetsuo , Ishikawa Shumpei
Published: May 2022

The stomach is an important digestive organ with a variety of biological functions. However, due to the complexity of its cellular and glandular composition, the precise cellular biology has yet to be elucidated. In this study, we conducted single-cell RNA sequence analysis of the human stomach and constructed a 137,610-cell dataset, the largest cell atlas reported to date. By integrating this single-cell analysis with spatial cellular distribution analysis, we were able to clarify novel aspects of the developmental and tissue homeostatic ecosystems in the human stomach. We identified LEFTY1+ as a potential stem cell marker in both gastric and intestinal metaplastic glands. We also revealed skewed distribution patterns for PDGFRA+BMP4+WNT5A+ fibroblasts that play pivotal roles in, or even precede, the phenotypic changes from gastric to metaplastic mucosa. Our extensive dataset will function as a fundamental resource in investigations of the stomach, including studies on development, aging, and carcinogenesis.
Subtle cognitive impairments in memory, attention, and executive functioning in patients with post-COVID syndrome and their relationships with clinical variables and subjective complaints
Authors: Kozik V. , Reuken P. , Utech I. , Gramlich J. , Stallmach Z. , Demeyere N. , Rakers F. , Schwab M. , Stallmach A. , Finke K.
Published: May 2022

Background and objectives

Cognitive symptoms persisting beyond three months following COVID-19 present a considerable disease burden. We aimed to establish a domain-specific cognitive profile of post-COVID syndrome (PCS) and relationships with subjective cognitive complaints and clinical variables to provide relevant information for the understanding of cognitive dysfunction and its predictors in a clinical cohort with PCS.

Methods

In this cross-sectional study, we compared cognitive performance on the clinically viable Oxford Cognitive Screen-Plus between a large post-COVID cohort (n= 282) and a socio-demographically matched healthy control group (n= 52). We assessed group differences in terms of fatigue and depression as well as relationships between cognitive dysfunction and clinical and patient-reported outcomes.

Results

On a group-level, patients scored significantly lower on delayed verbal memory (non-parametric effect sizer= .13), attention (r= .1), and executive functioning (r=.1) than healthy controls. In each of these domains, 10-20% of patients performed more than 1.5 SD below the healthy control mean. Delayed Memory was particularly affected and a small proportion of its variance was explained by hospitalisation (β= -.72,p< .01) and age (β= -.03,p< .05; R2adj. = .08). Attention scores were significantly predicted by hospitalisation (β= -.78,p< .01) and fatigue (β= -.04,p< .05; R2adj. = .06).

Discussion

PCS is associated with long-term cognitive dysfunction, particularly in delayed verbal memory, attention, and executive functioning. Deficits in delayed memory performance seem to be of particular relevance to patients’ subjective experience of impairment. Initial disease severity, current level of fatigue, and age seem to predict cognitive performance, while time since infection, depression, and pre-existing conditions do not. Longitudinal data are needed to map long-term course of cognitive dysfunction in PCS.
Involvement of nucleus accumbens D2-MSN projections to the ventral pallidum in anxious-like behavior
Authors: Correia Raquel , Domingues Ana Verónica , Coimbra Bárbara , Vieitas-Gaspar Natacha , Sousa Nuno , Pinto Luísa , Rodrigues Ana João , Soares-Cunha Carina
Published: May 2022

The nucleus accumbens (NAc) is a crucial brain region for emotionally-relevant behaviors. The NAc is mainly composed of medium spiny neurons (MSN) expressing either dopamine receptor D1 (D1-MSNs) or D2 (D2-MSNs). D1-MSNs project to the ventral tegmental area (VTA) and ventral pallidum (VP), while D2-MSNs project only to the VP. In this work, we selectively manipulated D1-MSN projections to the VP and VTA, and D2-MSN projections to the VP during classical anxiety behavioral paradigms in naïve mice.

We found that optogenetic activation of D1-MSN to VP or VTA did not trigger significant anxious-like behaviors. Interestingly, optical activation of D2-MSN-VP projections significantly increased anxious-like behavior in all of the tests performed. This phenotype was associated with a decrease in the activity of VP putative GABAergic neurons. Importantly, pre-treating D2-MSN-VP animals with the GABA modulator diazepam prevented the optically-triggered anxious-like behavior.

Overall, our results suggest that D2-MSN-VP projections contribute for the development of anxious-like behavior, through modulation of GABAergic activity in the VP.
Lactate supply overtakes glucose when neural computational and cognitive loads scale up
Authors: Dembitskaya Yulia , Piette Charlotte , Perez Sylvie , Berry Hugues , Magistretti Pierre J , Venance Laurent
Published: May 2022

The neural computational power is determined by neuroenergetics, but how and which energy substrates are allocated to various forms of memory engram is unclear. To solve this question, we asked whether neuronal fueling by glucose or lactate scales differently upon increasing neural computation and cognitive loads. Here, using electrophysiology, two-photon imaging, cognitive tasks and mathematical modeling, we show that both glucose and lactate are involved in engram formation, with lactate supporting long-term synaptic plasticity evoked by high stimulation load activity patterns and high attentional load in cognitive tasks, and glucose being sufficient for less demanding neural computation and learning tasks. Overall, these results demonstrate that glucose and lactate metabolisms are differentially engaged in neuronal fueling depending on the complexity of the activity-dependent plasticity and behavior.

One sentence summary

Neuronal fueling by lactate versus glucose scales differently according to engram level and memory load.
A case of microsatellite instability-high clinically advanced castration-resistant prostate cancer showing a remarkable response to pembrolizumab sustained over at least 18 months
Authors: Shimizu Kosuke , Sano Takeshi , Mizuno Kei , Sunada Takuro , Makita Noriyuki , Hagimoto Hiroki , Goto Takayuki , Sawada Atsuro , Fujimoto Masakazu , Ichioka Kentaro , Ogawa Osamu , Kobayashi Takashi , Akamatsu Shusuke
Published: May 2022

Defective DNA mismatch repair genes can lead to microsatellite instability (MSI)-high status in prostate cancer (PC). Accumulation of replication errors in DNA leads to the production of abundant neoantigens, which could be targets for immune checkpoint inhibitors (CPIs). However, the incidence of MSI-high PC is low, and not all patients show a satisfactory therapeutic response to CPIs. Here, we present the case of a patient with MSI-high castration-resistant PC who showed a remarkable and durable response to pembrolizumab. The patient was resistant to abiraterone, docetaxel, and cabazitaxel and was suffering from multiple tumor-associated or treatment-related complications, such as urinary tract infection, infective endocarditis, and uncontrollable prostatic hemorrhage. Soon after the start of pembrolizumab therapy, the patient showed a dramatic decrease in prostate-specific antigen from 35.67 ng/mL to an undetectable level and a remarkable reduction in the size of a massive prostate mass and lymph node metastases, with an absence of treatment-related complications. Specimens from the transurethral resection of prostate cancer during cabazitaxel treatment for control of prostate bleeding and also that from the prostate biopsy at initial diagnosis revealed MSI-high status. Immunohistochemistry showed loss of MSH2 and MSH6, and whole-exome sequencing revealed an approximate tumor mutation burden of 61 mutations/Mb as well as biallelic loss of MSH2. Pembrolizumab could show a significant effect even in a heavily treated patient with MSI-high advanced PC. Accumulation of detailed clinical and genomic information of cases of MSI-high PC treated with pembrolizumab is necessary for optimal patient selection.
Customer power, perceived behavioral control, and life insurance salespeople's reactions to customer sexual harassment
Authors: Lin Yi-Ling , Tseng Lu-Ming
Published: May 2022

Purpose

Sexual harassment is often the result of the abuse of power by perpetrators over victims. This study investigated the effects of customer reward power, customer coercive power, perceived behavioral control (PBC), and personal factors on full-time life insurance salespeople's intentions to report customer sexual harassment.

Design/methodology/approach

This study collected quantitative data through questionnaire surveys. A total of 743 valid questionnaires were collected.

Findings

Two types of customer sexual harassment (quid pro quo and hostile work environment) were evaluated. PBC was found to be the most influential factor affecting whistleblowing intentions. Regression analysis indicated that customer reward power significantly affected whistleblowing intentions toward quid pro quo customer sexual harassment. The male salespeople experienced stronger customer coercive power than did the female salespeople.

Originality/value

Not every society views customer power and customer sexual harassment in the same manner. By examining Taiwan's life insurance salespeople and including the concept of customer power, this study broadens the understanding of whistleblowing intentions toward the two types of customer sexual harassment.
NoPaperForms: enrolment engine for the education sector
Authors: Mital Amita , Panwar Archana , Jawalgi Yuvaraj
Published: May 2022

Learning outcomes

Discussion of the case will enable students to identify the cornerstones of industry development using simple frameworks like PESTLE and five forces that shape strategy. They will be able to identify critical success factors and evaluate how a firm gets competitive advantage. They will also be able to assess whether the advantage is sustainable for the firms and along which dimensions they have only competitive parity. The issues of contemporary firms growing through the use of network strategies is also highlighted and students will learn to appreciate the role of platforms and connectivity for gaining sustainable advantage.

Case overview/synopsis

This case describes the growth strategy of NoPaperForms, a start-up in the domain of enrolment automation for higher education in India. Naveen Goyal, the founder CEO sensed an opportunity in this growing industry segment and acquired it from the founder, Vishal Shah in 2017. The ultimate objective of an educational institute was to attract talent, Goyal evolved a comprehensive enrolment solution starting with the time a prospective student made an inquiry for enrolment till the time he/she paid for enrolment. It was a complete panel, bundled and packaged in a single system taking care of lead management, lead nurturing, application management, fee payment, post-application management and enrolment. He developed it into a unique blend of a customer relationship management (CRM), which was unique in the country. At this juncture, Goyal was exploring growth avenues. On the client side, he had the alternatives of focusing on the B2C segment or diversifying from B2B to B2C. Geographically, he had the options of expanding to tier II and tier III cities, which were the next growth hubs. The option of growing internationally was also on the cards. The purpose of the case is to analyse the opportunities in the education technology sector, specific to student enrolment and leverage the competencies of the firm to detail the future strategy of the firm.

Complexity academic level

The case can be used in a MBA program for a course in Strategic Management in the module of strategy formulation after fundamental concepts and theories of Strategic Management have been discussed.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 11: Strategy.
The effectiveness in international mediation of international organizations
Authors: Zhang Aoyuan , Qi Haixia
Published: May 2022

Purpose

This study aims to explore the factors whereby some international organizations (IOs) are more effective than others in international mediation and proposes three types of hypotheses through combining quantitative and qualitative analysis. First, IOs with greater institutional capabilities for gathering, exchanging and disseminating conflict-related information are more likely to mediate effectively. IO bias is another factor of influence in this regard. Second, IOs with greater institutional capabilities for deploying field missions and guaranteeing agreement are more likely to mediate effectively and maintain durable peace. Third, IOs with higher amounts of leverage are more likely to mediate effectively.

Design/methodology/approach

The study establishes two data sets: one on interstate conflict; the other on intrastate conflict, thus to cover as many research samples as possible and avoid sampling bias.

Findings

Results of the statistical analysis indicate that no matter interstate or intrastate conflict, IOs with higher institutional capabilities for diplomatic interventions are more likely to bring conflict parties to an agreement and thereafter maintain short-term peace. IOs with higher institutional capabilities for economic sanctions are similarly effective. Furthermore, IOs with greater institutional capabilities for field mission deployment mediate more effectively, whether in facilitating peace agreements or maintaining short-term and long-term peace after the agreement. IO bias and preference, however, have no significant impact on mediation effectiveness.

Research limitations/implications

This study has made no in-depth explorations of such existing and important research areas as different third-party comparisons of the mediation effect.

Practical implications

This paper attempts to make some contributions to the topic of mediation effectiveness through applying a bargaining model to the research and performing a statistical analysis based on both an interstate conflict data set and an intrastate conflict data set.

Originality/value

This paper provides an in-depth causal analysis and thoroughgoing comparison of the effectiveness of IOs in both interstate conflicts and intrastate conflicts.
Work engagement among different types of solo self-employed: the mediating role of intrinsic job resources
Authors: Gevaert Jessie , Vanroelen Christophe , Stas Lara , De Moortel Deborah
Published: May 2022

Purpose

The ideal-typical entrepreneur presents him/herself in the neoliberal iconography as an autonomous and pro-active individual who is highly engaged with his/her vocation. Nevertheless, empirical research on the actual work engagement of the self-employed is scarce. In addition, phenomena like “necessity self-employment” and “economically dependent self-employment” raise concerns about the potential eudaimonic well-being outcomes of these self-employed. In this study, it was therefore investigated to what extent necessity self-employment and economically dependent self-employment are associated to work engagement and whether this relation is mediated by intrinsic job resources.

Design/methodology/approach

The authors used data from the 2015 European Working Conditions Survey (EWCS) involving 5,463 solo self-employed participants. For analyzing the data, structural equation modeling (SEM) with the Lavaan package was used.

Findings

Both necessity self-employment and economically dependent self-employment were linked to poor work engagement, however, intrinsic job resources mediated both effects.

Originality/value

While previous studies have shown differences in hedonic well-being between opportunity/necessity entrepreneurs, and economically (in)dependent entrepreneurs, this study considers their distinct profiles regarding eudaimonic well-being. Eudaimonic well-being was deemed particularly relevant because of its implications for other outcomes such as life satisfaction, psychological well-being, ill-health, business performance and persistence in self-employment.
Managing stressors, stress and strain faced by facility managers
Authors: Ling Florence YY , Mok Elsie Kai Ying
Published: May 2022

Purpose

This study aims to investigate how to manage the stressors that facility managers (FMs) face with the aim of reducing their stress and strain levels.

Design/methodology/approach

Using the job demands-resources (JD-R) model, stressors are operationalized from job demands, job resources and personal resources constructs. A structured questionnaire was used to collect data from FMs based in Singapore.

Findings

FMs have significantly high levels of stress, but they are able to manage this well. Job demands that cause stress and strain are those relating to insufficient time to complete the work and difficulties in handling the work. The lack of job resources in terms of lack of organizational support and inadequate stress mitigation programs are associated with high levels of stress and strain.

Research limitations/implications

The limitations are the relatively small sample size and absence of a database of FMs in Singapore, and correlation is not causation when determining the association between stressors and stress and strain.

Practical implications

Based on the recommendations, employers and FMs may manage the specific stressors identified so that FMs’ stress and strain levels are under control to enable them to work optimally.

Originality/value

This research discovered that the JD-R model is moderated by certain features of facilities management and FMs. When these features are present, FMs are predisposed to more stressors, and higher stress and strain. For the facilities management profession, the discovery is that there are significantly more job demands: for in-house FMs compared to those working for outsourced firms; for FMs who need to carry out estate and asset management, landlord activities and facility planning compared to FMs who focus on operations and maintenance; and for FMs who work longer than five days compared to those who work a five-day week.
Governance and culture within employee-owned companies
Authors: Van Doel Richard M. , Howell George
Published: May 2022

Purpose

The purpose of this paper is to examine the type of governance dominant within employee-owned companies established as an Employee Stock Ownership Plan (ESOPs) and to ascertain if governance follows the agency or stewardship theory of governance.

Design/methodology/approach

A sequential mixed method (Quantitative/Qualitative) research design was used with a convenience sample of employee-owned companies who were members of The ESOP Association (TEA). The Stewardship Climate Scale (SCS) was used as the quantitative instrument and structured interviews were used as the qualitative instrument.

Findings

A majority (96%) of ESOPs participating in the study self-identified as stewardship governance, only 6 of the 154 companies (4%) self-identified as having agency governance.

Research limitations/implications

There is a potential of self-report bias based on the use of convenience sampling which should be minimized based on the large number of participants. The study was not able to examine the relationship between stewardship and productivity.

Originality/value

This is the first large scale research study examining governance within employee-owned companies.
Perspectives on the potential of Mangiferin as a nutraceutical: a review
Authors: Jamwal Deepti , Saini Priyanka , Tomar Pushpa C. , Ghosh Arpita
Published: May 2022

Purpose

The aim of this study is to provide a review of the research studies that took place in the previous years regarding Mangiferin and its potential use in the treatment of various disorders such as diabetes, cardiovascular diseases, cancer and human immunodeficiency virus.

Design/methodology/Approach

Mangiferin can be easily extracted from the plant at a very low cost to treat some common as well as deadly diseases, which will be a miracle in herbal treatment. In support of this, the recent related articles were considered to understand the bioactive compound “Mangiferin” to treat lifestyle diseases. Various review articles and research papers were collected from international and national journals, and internet sources were also being used to compile the current manuscript.

Findings

Mangiferin has been shown to have the potential to mitigate many life style diseases such as diabetes, obesity, hypertension, fatty liver, atherosclerosis, dyslipidemia and diabetes-related end-organ complications such as retinopathy, neuropathy and nephropathy.

Originality/value

In this comprehensive review, this study evaluates Mangiferin and its lifestyle disease-modifying properties for nutraceuticals purposes.
Social media exposure assessment: influence on attitudes toward generic vaccination during the COVID-19 pandemic
Authors: Sitar-Taut Dan-Andrei , Mican Daniel
Published: May 2022

Purpose

Even though social media (SM) has been explored in-depth, its role remains unclear regarding short- and long-term preventive attitudes in global health emergencies. To fill this gap, the Stimulus-Organism-Response framework aims to clarify the social media exposure mission in acknowledging risk perception and triggering preventive attitudes and behaviors toward COVID-19 and general vaccination.

Design/methodology/approach

The authors conducted an explanatory-predictive study on 480 Romanian students, using partial least squares structural equation modeling, and performed model evaluation, multi-group, model selection, and importance-performance map analyses.

Findings

The study provides insights in understanding significant relationships and drivers explaining and predicting attitudes towards vaccines. The main relationships are between fear and risk perception; risk and preventive attitudes and behaviors; and vaccination degree and attitudes to vaccines. The most important factor is the vaccination degree and media exposure is the most performant.

Practical implications

Developing and applying regulations and communication strategies for quality mass information may positively increase attitudes toward vaccines by indirectly enforcing the main drivers.

Social implications

Organizations, authorities, and opinion leaders must have a coherent supportive presence in media.

Originality/value

This study filled the literature gap by building a generic theoretical and empirical proven framework that investigates the mediated effect towards vaccines of all media types by COVID-19 experience and vaccination degree.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/OIR-11-2021-0621