bluuebunny/crossref_metadata_2025 huggingface dataset:
The dynamic role of the Japanese property sector REITs in mixed-assets portfolio
Authors: Razak Muhammad Zaim
Published: January 2023

Purpose

This study examined the dynamic role of the Japanese property sector, particularly the real estate investment trusts (REITs), in mixed-asset portfolios of stocks and bonds, as well as office, retail, hotel and residential REITs.

Design/methodology/approach

Daily data were retrieved from 01 January 2008 to 31 December 2019. The sample time frame consisted of in-sample and out-of-sample periods. The dynamic conditional correlation-generalised autoregressive conditional heteroskedastic (DCC-GJRGARCH) model was deployed to obtain the forecast estimates of time-varying volatility of REITs and correlations with other assets. The estimates were employed to construct out-of-sample portfolios based on the three assets for daily investment. The five sets of portfolios with each individual property sector REITs, as well as a portfolio of stocks and bonds that served as a benchmark, were produced. The average utility for each set of portfolios was estimated and compared with the average utility of the benchmark portfolio. The average transaction cost (TC) for portfolio rebalancing was calculated as well.

Findings

The forecast of volatility estimates for each property sector revealed that each asset displayed a similar pattern with the differences in the volatility magnitude. Notably, hotel and retail REITs were more volatile than other property sector REITs. The property sector REITs exhibited a positive correlation with stocks but negatively linked with bonds. The results unveiled the diversification benefits of incorporating property sector REITs. The portfolio with property sector REITs had higher risk-adjusted returns and utility, compared to portfolio consisting of stocks and bonds. The benefits outweighed the TC for portfolio rebalancing.

Practical implications

This study highlights the importance of quantifying the conditional time-varying volatility and correlations of the property sector REITs with other asset returns, especially for investment decision, to select and include property sector REITs in mixed-asset portfolios. For fund managers seeking liquid assets in daily investment, this analysis suggests the inclusion of hotel and retail REITs to enhance REITs' portfolio performance.

Originality/value

This study is the first to investigate the dynamic characteristics of the volatility and correlation of each property sector REITs with other financial assets by employing the conditional framework that accounted for short- and long-run persistency in economic shocks. The reported outcomes shed light on the differences in the underlying properties that contribute to the variances in dynamic volatility of each sector REITs, as well as REITs' correlations with stocks and bonds. This application enables the authors to transmit the dynamics of variance-covariance matrix amongst each property sector REITs, stocks and bonds into asset allocation problem on a daily basis.
What drives team learning: core conditions and paths
Authors: Pinheiro Margarida , Rebelo Teresa , Lourenço Paulo Renato , Dimas Isabel
Published: January 2023

Purpose

The purpose of this study is to analyze the configurational effect of transformational leadership, team conflict, team cohesion and psychological safety on team learning.

Design/methodology/approach

The questionnaire and two different data sources (team members and team leaders) were used as data collection strategy. Based on a sample of 82 teams, qualitative comparative analysis in its fuzzy set variant was used to test the model.

Findings

The findings of this study reveal that three important paths explain team learning: the presence of transformational leadership, task cohesion and psychological safety with the absence of relationship conflict; the presence of transformational leadership, social and task cohesion and psychological safety; and the presence of transformational leadership, social and task cohesion with the absence of relationship and task conflict.

Originality/value

Overall, the findings suggest that the presence of transformational leadership, team cohesion and psychological safety and the absence of conflict are important conditions for team learning to occur, as well as that more than one configurations of antecedent factors drive team learning.
The interactive effects of intragroup cooperation and competition: toward a perspective of paradox
Authors: Ouyang Xi , Liu Zhiqiang , Gui Chenglin
Published: January 2023

Purpose

Underpinned by paradox theory, this study aims to investigate how and when intragroup cooperation and competition combine to drive individual creativity. It further examines how group goal orientation influences individuals’ creative processes by underscoring its effect on individuals' tendency to adopt a paradox lens.

Design/methodology/approach

A time-lagged survey was conducted with 85 leaders and 420 employees in Chinese high-tech companies that were actively engaged in innovative activities.

Findings

The results reveal that pure cooperation or pure competition exerts no significant influence on creativity, yet simultaneous high levels of cooperation and competition give rise to strong levels of creativity. This combined effect of cooperation and competition on employees' creativity could be explained by their changes in cognitive flexibility. Moreover, employees' flexible responses to high levels of cooperation and competition could be promoted when groups enact learning goals rather than performance goals.

Originality/value

This study provides a theoretical perspective on how cooperation and competition can be contingent upon each other. It also highlights the role of group learning goals when members strive to be creative in groups with high levels of competition and cooperation.
Automated detection of learning stages and interaction difficulty from eye-tracking data within a mixed reality learning environment
Authors: Ogunseiju Omobolanle Ruth , Gonsalves Nihar , Akanmu Abiola Abosede , Abraham Yewande , Nnaji Chukwuma
Published: January 2023

Purpose

Construction companies are increasingly adopting sensing technologies like laser scanners, making it necessary to upskill the future workforce in this area. However, limited jobsite access hinders experiential learning of laser scanning, necessitating the need for an alternative learning environment. Previously, the authors explored mixed reality (MR) as an alternative learning environment for laser scanning, but to promote seamless learning, such learning environments must be proactive and intelligent. Toward this, the potentials of classification models for detecting user difficulties and learning stages in the MR environment were investigated in this study.

Design/methodology/approach

The study adopted machine learning classifiers on eye-tracking data and think-aloud data for detecting learning stages and interaction difficulties during the usability study of laser scanning in the MR environment.

Findings

The classification models demonstrated high performance, with neural network classifier showing superior performance (accuracy of 99.9%) during the detection of learning stages and an ensemble showing the highest accuracy of 84.6% for detecting interaction difficulty during laser scanning.

Research limitations/implications

The findings of this study revealed that eye movement data possess significant information about learning stages and interaction difficulties and provide evidence of the potentials of smart MR environments for improved learning experiences in construction education. The research implication further lies in the potential of an intelligent learning environment for providing personalized learning experiences that often culminate in improved learning outcomes. This study further highlights the potential of such an intelligent learning environment in promoting inclusive learning, whereby students with different cognitive capabilities can experience learning tailored to their specific needs irrespective of their individual differences.

Originality/value

The classification models will help detect learners requiring additional support to acquire the necessary technical skills for deploying laser scanners in the construction industry and inform the specific training needs of users to enhance seamless interaction with the learning environment.
From efficiencies to transformation – tapping the full potential of process mining
Authors: Higgins Lisa , Marshall Anthony , Crysel Kirsten , Dencik Jacob
Published: January 2023

Purpose

Because of its effectiveness, process mining is rapidly becoming ubiquitous. A recent IBM Institute for Business Value (IBV) survey found that 65 percent of organizations report actively using process mining to improve processes. And in partnership with software-as-a-service (SaaS) providers to add even greater insight into their processes, 69 percent compare their organization’s data with other SaaS customers. And as many as 77 percent of supply chain executives say they are at least at the implementation stage of process and task mining.

Design/methodology/approach

The IBM Institute for Business Value and APQC, in cooperation with Oxford Economics, surveyed 2,000 C-level executives in first half of 2022 from 13 countries in all major geographies and across 22 industries. The IBV and APQC implemented an in-depth analysis of how organizations use benchmarking and process mining tools, the benefits they gain from use of these tools and how they anticipate using them in the future.

Findings

Big data and digital technologies also creates new possibilities for measuring performance and revealing process improvement opportunities through process mining ? a relatively new discipline that applies data science to discover, validate and improve workflows in real time.

Practical/implications

By utilizing data from IT systems to create a process model and then examining the end-to-end process, process mining enables root causes of variations from norms to be identified using specialized algorithms, and these insights enable management to see if processes are functioning as intended and identify new opportunities to optimize them.

Originality/value

More recently, the scope of process mining initiatives has widened to encompass more sophisticated mission-critical functions, notably human capital, cybersecurity and sales. Organizations that embrace process mining outperform others across key business measures, including profitability, innovation, agility, customer satisfaction and technological sophistication. 10;
Roots originating from different shoot parts are functionally different in running bamboo, Phyllostachys glauca
Authors: Wang Guangru , Yu Fen , Wu Hongyan , Hu Shuzhen , Wu Shujin , Pei Nancai , Shi Jianmin , Lambers Hans
Published: January 2023

Running bamboos are a group of clonal plants exhibiting rapid and widespread expansion. They possess two root subsystems, arising from different shoot parts, culm roots and rhizome roots. To date, it remains unclear what the functional differences are between the two root subsystems and what their relation is to the remarkably competitive ability of running bamboos.

A typical running bamboo, Phyllostachys glauca, which dominates in a highly heterogeneous habitat of limestone hills, was sampled to compare the morphology, architecture, anatomy, chemical composition, mechanics and nutrient acquisition of the two root subsystems to explore their differences in functional traits.

Compared with rhizome roots, culm roots possessed greater tensile strength, modulus of elasticity, stele diameter to root diameter ratio, root tissue density, root length density, rooting depth, basal diameter of shoot‐borne roots and more lignified cells. Culm roots also had a higher phosphorus (P) concentration (>0.4 mg g−1), which was nearly twice that of rhizome roots. By contrast, rhizome roots exhibited a greater specific root area, specific root length, cortex thickness to root radius ratio, total branch order and greater P‐uptake capacity than culm roots.

Our findings revealed distinct differences in functional traits between culm roots and rhizome roots in P. glauca. Culm roots are considered to primarily provide anchorage, but also function in resource acquisition and nutrient storage, while rhizome roots mainly play a role in resource acquisition. Except for the anchorage and resource acquisition of culm roots, the extra resource acquisition by rhizome roots and the high concentration of a limiting nutrient (P) in culm roots enhance the performance in a highly heterogeneous habitat which offers a physiological explanation for P. glauca dominating on limestone hills.

The functional differentiation between culm roots and rhizome roots provides insight into the mechanism underpinning the remarkable expansion of running bamboos and offers a new perspective to explain the strong competitive ability of clonal plants with dimorphic roots.

Read the free Plain Language Summary for this article on the Journal blog.
Marine protected areas' positive effect on fish biomass persists across the steep climatic gradient of the Mediterranean Sea
Authors: Frid Ori , Malamud Shahar , Di Franco Antonio , Guidetti Paolo , Azzurro Ernesto , Claudet Joachim , Micheli Fiorenza , Yahel Ruth , Sala Enric , Belmaker Jonathan
Published: January 2023

The positive effect of fully protected marine protected areas (MPAs) on marine biodiversity, and specifically on fishes, has been widely documented. In contrast, the potential of MPAs to mitigate the impact of adverse climatic conditions has seldom been investigated.

Here, we assessed the effectiveness of MPAs, quantified as increasing fish biomass, across wide geographic and environmental gradients across the Mediterranean Sea. We performed underwater visual surveys within and outside MPAs to characterize fish assemblages in 52 rocky reef sites across an extent of over 3300 km. We used the steep spatial temperature gradient across the Mediterranean as a ‘space‐for‐time’ substitution to infer climate‐driven temporal changes.

We found that, as expected, Mediterranean MPAs increased fish biomass. At the same time, higher seawater temperatures are associated with decreased fish biomass, changes in species composition, and shifts towards more thermophilic species. Importantly, we found that the rate of decrease in fish biomass with temperature was similar between protected and fished sites.

Taken together, these results suggest that the capacity of MPAs to harbour higher fish biomass, compared to surrounding areas, is maintained across a broad temperature range. At the same time, MPAs will not be able to offset larger‐scale biotic alterations associated with climate change.

Policy implications. Our results suggest that sustained warming will likely reduce fish biomass in the Mediterranean Sea and shift community structure, requiring more conservative targets for fishery regulations. At the same time, protection from fishing will remain an important management tool even with future high‐water temperatures, and MPAs are expected to continue to provide local‐scale benefits to conservation and fisheries.
EXPERIENCING URBAN SMELLS WHEN WALKING: Kastamonu City Case
Authors: Çeven Elif Ayan , Belkayali Nur
Published: January 2023

Urban experiences are increasing in popularity every day. In these experiences sensory elements are significant, and a review of the urban environment, in which visual perceptions have prevailed in the past, would demonstrate that other senses are important as well. As Le Corbusier remarked, urban experiences can be achieved by walking with a wide perspective. In the present study scent walks were conducted to reveal the significance of the scent factor in urban experience. As a result of these walks, the existing scents in Kastamonu city, the role of the scents in urban memory, and their effects on individuals were determined, thus emphasizing the significance of scents for urban planning and design.
The development of ankylosing spondylitis in a patient with familial hemophilia
Authors: Cüre Osman , Ilkkilic Kadir
Published: January 2023

Hemophilia is a rare inherited disease which causes bleeding due to Factor VIII or Factor IX deficiency. It is usually X‐linked recessive and typically affects males. Arthropathy occurs as a result of cartilage damage and chronic synovitis due to recurrent intra‐articular bleeding in hemophilic patients and is mostly seen in the knee, shoulder, hip and ankle joints. There are many other diseases that cause chronic synovitis ankylosing spondylitis (AS), which is a subtype of spondyloarthropathies that cause chronic low back pain, more common in men younger than 45 years of age. In addition to axial involvement, peripheral arthritis, uveitis, enthesitis and dactylitis can be seen. Although the etiology is not fully known, genetic and environmental factors are responsible for the pathogenesis. In this study, we aimed to present congenital hemophilia and AS coexistence in a 22‐year‐old male patient.
Unprecedented long‐term survival in a patient with malignant pleural mesothelioma treated with subsequent systemic chemo‐ and immunotherapeutic regimens
Authors: Cerbone Luigi , Delfanti Sara , De Angelis Antonina M. , Crivellari Stefania , Boccuzzi Francesco , Cimorelli Angela , Bertolotti Marinella , Righi Luisella , Bertino Pietro , Grosso Federica
Published: January 2023

Pleural mesothelioma is a rare disease with a dismal prognosis and few therapeutic options. Until recently the median overall survival for a pleural mesothelioma patient was up to 2 years, with few exceptional cases of patients achieving a longer survival. Here, we report the clinical case of a patient whose survival spanned over 10 years. The patient underwent several systemic treatments, including three different chemotherapy lines (cisplatin‐pemetrexed, vinorelbine and platinum rechallenge) and two immunotherapy regimens using immune checkpoint inhibitors (anti CTLA‐4 tremelimumab and anti PD‐1 nivolumab). At the time this report was written, the patient was off‐treatment, asymptomatic and with a stable radiological disease. Our case demonstrates that a prolonged survival with a preserved quality of life may be reached in selected patients through the exploitation of the available treatments in an expertise setting.
A randomised controlled trial of the non‐inferiority of erector spinae plane block vs. thoracic paravertebral block for laparoscopic nephro‐ureterectomy
Authors: Xu Z.‐Z. , Li X. , Chen B.‐L. , Yang K.‐L. , Wang J. , Li X.‐Y. , Zhang H. , Wang D.‐X.
Published: January 2023

Erector spinae plane block and paravertebral block can provide analgesia for abdominal surgery. It is unclear whether erector spinae block is inferior to paravertebral block. We aimed to determine whether sufentanil dose and pain intensity (11‐point scale) to 24 h after erector spinae block exceeded those after paravertebral block by no more than 5 μg and 1 point, respectively. We randomly allocated 166 adults to 0.4 ml.kg−1 ropivacaine 0.375% before scheduled laparoscopic nephroureterectomy, 83 each to erector spinae or paravertebral injection. We measured incision pain and intra‐abdominal pain at rest and on movement 0.5 h, 2 h, 6 h, 18 h, 24 h and 48 h after surgery. Median (IQR [range]) cumulative sufentanil dose after erector spinae block was 15 (5–30 [0–105]) μg vs. 20 (10–50 [0–145]) μg after paravertebral block, median (95%CI) difference 5 μg (0–10), erector spinae non‐inferiority p < 0.001. Median (IQR [range]) pain were 1.5 (1.0–2.0 [0.0–5.3]) after erector spinae block vs. 2.0 (1.0–2.5 [0.0–6.0]) after paravertebral block, median (95% CI) difference 0.3 (0.0–0.5), erector spinae non‐inferiority p < 0.001. Adverse events did not differ between groups. Erector spinae block analgesia was not inferior to paravertebral block analgesia after laparoscopic nephroureterectomy.
Two‐pore channel protein TPC1 is a determining factor for the adaptation of proximal tubular phosphate handling
Authors: Just Armin , Mallmann Robert T. , Grossmann Sonja , Sleman Faten , Klugbauer Norbert
Published: January 2023

Aim

Two‐pore channels (TPCs) constitute a small family of cation channels expressed in endo‐lysosomal compartments. TPCs have been characterized as critical elements controlling Ca2+‐mediated vesicular membrane fusion and thereby regulating endo‐lysosomal vesicle trafficking. Exo‐ and endocytotic trafficking and lysosomal degradation are major mechanisms of adaption of epithelial transport. A prime example of highly regulated epithelial transport is the tubular system of the kidney. We therefore studied the localization of TPC protein 1 (TPC1) in the kidney and its functional role in the dynamic regulation of tubular transport.

Methods

Immunohistochemistry in combination with tubular markers were used to investigate TPC1 expression in proximal and distal tubules. The excretion of phosphate and ammonium, as well as urine volume and pH were studied in vivo, in response to dynamic challenges induced by bolus injection of parathyroid hormone or acid–base transitions via consecutive infusion of NaCl, Na2CO3, and NH4Cl.

Results

In TPC1‐deficient mice, the PTH‐induced rise in phosphate excretion was prolonged and exaggerated, and its recovery delayed in comparison with wildtype littermates. In the acid–base transition experiment, TPC1‐deficient mice showed an identical rise in phosphate excretion in response to Na2CO3 compared with wildtypes, but a delayed NH4Cl‐induced recovery. Ammonium‐excretion decreased with Na2CO3, and increased with NH4Cl, but without differences between genotypes.

Conclusions

We conclude that TPC1 is expressed subapically in the proximal but not distal tubule and plays an important role in the dynamic adaptation of proximal tubular phosphate reabsorption towards enhanced, but not reduced absorption.
Tissue‐specific effects of exercise as NAD+‐boosting strategy: Current knowledge and future perspectives
Authors: Walzik David , Jonas Wiebke , Joisten Niklas , Belen Sergen , Wüst Rob C. I. , Guillemin Gilles , Zimmer Philipp
Published: January 2023

Nicotinamide adenine dinucleotide (NAD+) is an evolutionarily highly conserved coenzyme with multi‐faceted cell functions, including energy metabolism, molecular signaling processes, epigenetic regulation, and DNA repair. Since the discovery that lower NAD+ levels are a shared characteristic of various diseases and aging per se, several NAD+‐boosting strategies have emerged. Other than pharmacological and nutritional approaches, exercise is thought to restore NAD+ homeostasis through metabolic adaption to chronically recurring states of increased energy demand. In this review we discuss the impact of acute exercise and exercise training on tissue‐specific NAD+ metabolism of rodents and humans to highlight the potential value as NAD+‐boosting strategy. By interconnecting results from different investigations, we aim to draw attention to tissue‐specific alterations in NAD+ metabolism and the associated implications for whole‐body NAD+ homeostasis. Acute exercise led to profound alterations of intracellular NAD+ metabolism in various investigations, with the magnitude and direction of changes being strongly dependent on the applied exercise modality, cell type, and investigated animal model or human population. Exercise training elevated NAD+ levels and NAD+ metabolism enzymes in various tissues. Based on these results, we discuss molecular mechanisms that might connect acute exercise‐induced disruptions of NAD+/NADH homeostasis to chronic exercise adaptions in NAD+ metabolism. Taking this hypothesis‐driven approach, we hope to inspire future research on the molecular mechanisms of exercise as NAD+‐modifying lifestyle intervention, thereby elucidating the potential therapeutic value in NAD+‐related pathologies.
Cranberry‐lingonberry juice affects the gut and urinary microbiome in children ‐ a randomized controlled trial
Authors: Hakkola Mikael , Vehviläinen Pekka , Muotka Janita , Tejesvi Mysore V. , Pokka Tytti , Vähäsarja Päivi , Hanni Anna‐Maija , Renko Marjo , Uhari Matti , Salo Jarmo , Tapiainen Terhi
Published: January 2023

The mechanism by which cranberry‐lingonberry juice (CLJ) prevents urinary tract infections (UTI) in children remains unknown. We hypothesized that it alters the composition of the gut or urinary microbiome. Altogether, 113 children with UTIs were randomly allocated to drink either CLJ or a placebo juice for 6 months. We collected urinary samples at 3 months and fecal samples at 3, 6 and 12 months and used next‐generation sequencing of the bacterial 16S gene. The children who consumed CLJ had a lower abundance of Proteobacteria (p = 0.03) and a higher abundance of Firmicutes phylum (p = 0.04) in their urinary microbiome at 3 months than did those in the placebo group. The abundance of Escherichia coli in the urinary microbiome was 6% in the CLJ group and 13% in the placebo group (p = 0.42). In the gut microbiome the abundance of Actinobacteria at 3 and 12 months was higher in the children receiving CLJ. The diversity of the urinary and gut microbiome did not differ between the groups. The children drinking CLJ had a different urinary and gut microbiome from those receiving a placebo juice. A healthy urinary microbiome may be important in preventing UTIs in children.
The neurovasculature as a target in temporal lobe epilepsy
Authors: Reiss Yvonne , Bauer Sebastian , David Bastian , Devraj Kavi , Fidan Elif , Hattingen Elke , Liebner Stefan , Melzer Nico , Meuth Sven G. , Rosenow Felix , Rüber Theodor , Willems Laurent M. , Plate Karl H.
Published: January 2023

The blood–brain barrier (BBB) is a physiological barrier maintaining a specialized brain micromilieu that is necessary for proper neuronal function. Endothelial tight junctions and specific transcellular/efflux transport systems provide a protective barrier against toxins, pathogens, and immune cells. The barrier function is critically supported by other cell types of the neurovascular unit, including pericytes, astrocytes, microglia, and interneurons. The dysfunctionality of the BBB is a hallmark of neurological diseases, such as ischemia, brain tumors, neurodegenerative diseases, infections, and autoimmune neuroinflammatory disorders. Moreover, BBB dysfunction is critically involved in epilepsy, a brain disorder characterized by spontaneously occurring seizures because of abnormally synchronized neuronal activity. While resistance to antiseizure drugs that aim to reduce neuronal hyperexcitability remains a clinical challenge, drugs targeting the neurovasculature in epilepsy patients have not been explored. The use of novel imaging techniques permits early detection of BBB leakage in epilepsy; however, the detailed mechanistic understanding of causes and consequences of BBB compromise remains unknown. Here, we discuss the current knowledge of BBB involvement in temporal lobe epilepsy with the emphasis on the neurovasculature as a therapeutic target.
RNAi screening reveals a synthetic chemical–genetic interaction between ATP synthase and PFK1 in cancer cells
Authors: Kobayashi Hiroki , Takase Shohei , Nishimura Haruna , Matsumoto Ken , Harada Hironori , Yoshida Minoru
Published: January 2023

To meet cellular bioenergetic and biosynthetic demands, cancer cells remodel their metabolism to increase glycolytic flux, a phenomenon known as the Warburg effect and believed to contribute to cancer malignancy. Among glycolytic enzymes, phosphofructokinase‐1 (PFK1) has been shown to act as a rate‐limiting enzyme and to facilitate the Warburg effect in cancer cells. In this study, however, we found that decreased PFK1 activity did not affect cell survival or proliferation in cancer cells. This raised a question regarding the importance of PFK1 in malignancy. To gain insights into the role of PFK1 in cancer metabolism and the possibility of adopting it as a novel anticancer therapeutic target, we screened for genes that caused lethality when they were knocked down in the presence of tryptolinamide (TLAM), a PFK1 inhibitor. The screen revealed a synthetic chemical–genetic interaction between genes encoding subunits of ATP synthase (complex V) and TLAM. Indeed, after TLAM treatment, the sensitivity of HeLa cells to oligomycin A (OMA), an ATP synthase inhibitor, was 13,000 times higher than that of untreated cells. Furthermore, this sensitivity potentiation by TLAM treatment was recapitulated by genetic mutations of PFK1. By contrast, TLAM did not potentiate the sensitivity of normal fibroblast cell lines to OMA, possibly due to their reduced energy demands compared to cancer cells. We also showed that the PFK1‐mediated glycolytic pathway can act as an energy reservoir. Selective potentiation of the efficacy of ATP synthase inhibitors by PFK1 inhibition may serve as a foundation for novel anticancer therapeutic strategies.
Downregulated mitochondrial transcription factor A enhances mycoplasma infection to promote the metastasis of hepatocellular carcinoma
Authors: Wang Yinping , Wang Gang , Hong Xin , Zhao Jing , Wu Dan , Chen Lin , Liu Xiaoli , Kong Deyu , Huang Qichao , Xing Jinliang , Wang Nan , Zhao Yilin
Published: January 2023

Mycoplasma is widespread in various hosts and may cause various diseases in animals. Interestingly, the occurrence of mycoplasma infection was observed in many tumor types. However, the mechanism regulating its infection is far from clear. We unexpectedly found that the knockdown of mitochondrial transcription factor A (TFAM) remarkably enhanced mycoplasma infection in hepatocellular carcinoma (HCC) cells. More importantly, we found that mycoplasma infection facilitated by TFAM knockdown significantly promoted HCC cell metastasis. Mycoplasma infection was further found to be positively correlated with poor prognosis in patients with HCC. Mechanistically, the decreased TFAM expression upregulated the transcription factor Sp1 to increase the expression level of Annexin A2 (ANXA2), which was reported to interact with membrane protein of mycoplasma. Moreover, we found that mycoplasma infection enhanced by the TFAM downregulation promoted HCC migration and invasion by activating the nuclear factor‐κB signaling pathway. The downregulation of TFAM enhanced mycoplasma infection in HCC cells and promoted HCC cell metastasis. Our study contributes to the understanding of the pathological role of mycoplasma infection and provides supporting evidence that targeting TFAM could be a potential strategy for the treatment of HCC with mycoplasma infection.
Association of KMT2C/D loss‐of‐function variants with response to immune checkpoint blockades in colorectal cancer
Authors: Liu Ruiqi , Niu Yanling , Liu Chao , Zhang Xin , Zhang Jinku , Shi Min , Zou Wenbo , Gu Binbin , Zhu Honglin , Wang Danhua , Yuan Hongling , Li Wei , Zhao Dandan , Zheng Qiaosong , Liu Rong , Chen Weiping , Ma Tonghui , Zhang Yanqiao
Published: January 2023

Immune checkpoint inhibitors (ICIs) have become important treatment strategies, yet responses vary among patients and predictive biomarkers are urgently needed. Mutations in KMT2C and KMT2D lead to increased levels of genomic instability. Therefore, we aimed to examine whether KMT2C/D mutations might be a predictor of immunotherapeutic efficacy. Here, we investigated the associations of KMT2C/D loss‐of‐function (LOF) variants with tumor mutation burden (TMB), MSI‐H, PD‐L1 expression, the levels of tumor‐infiltrating leukocytes (TILs), and clinical response to ICIs. It was found that KMT2C/D LOF variants were associated with higher TMB. Compared with the non‐LOF group, the proportion of patients with MSI‐H tumors was larger in the LOF group. PD‐L1 expression was higher in the LOF group only for colorectal cancer in both the Chinese and The Cancer Genome Atlas cohorts. Importantly, KMT2C/D LOF variants were associated with decreased regulatory T cells and increased levels of CD8+ T cells, activated NK cells, M1 macrophages, and M2 macrophages in colorectal cancer. However, there was no significant association between KMT2C/D LOF and TILs levels in other cancer types. Consistently, the results showed that KMT2C/D LOF variants were associated with prolonged overall survival only in colorectal cancer (p = 0.0485). We also presented that patients with KMT2C/D LOF mutations exhibited a better clinical response to anti‐PD‐1 therapy in a Chinese colorectal cancer cohort (p = 0.002). Taken together, these results suggested that KMT2C/D LOF variants could be a useful predictor for ICIs efficacy in colorectal cancer. In addition, the predictive value of KMT2C/D LOF variants was consistent with their association with TILs levels.
Clinical utility of Todai OncoPanel in the setting of approved comprehensive cancer genomic profiling tests in Japan
Authors: Kage Hidenori , Shinozaki‐Ushiku Aya , Ishigaki Kazunaga , Sato Yusuke , Tanabe Masahiko , Tanaka Shota , Tanikawa Michihiro , Watanabe Kousuke , Kato Shingo , Akagi Kiwamu , Uchino Keita , Mitani Kinuko , Takahashi Shunji , Miura Yuji , Ikeda Sadakatsu , Kojima Yasushi , Watanabe Kiyotaka , Mochizuki Hitoshi , Yamaguchi Hironori , Kawazoe Yoshimasa , Kashiwabara Kosuke , Kohsaka Shinji , Tatsuno Kenji , Ushiku Tetsuo , Ohe Kazuhiko , Yatomi Yutaka , Seto Yasuyuki , Aburatani Hiroyuki , Mano Hiroyuki , Miyagawa Kiyoshi , Oda Katsutoshi
Published: January 2023

Comprehensive cancer genome profiling (CGP) has been nationally reimbursed in Japan since June 2019. Less than 10% of the patients have been reported to undergo recommended treatment. Todai OncoPanel (TOP) is a dual DNA–RNA panel as well as a paired tumor–normal matched test. Two hundred patients underwent TOP as part of Advanced Medical Care B with approval from the Ministry of Health, Labour and Welfare between September 2018 and December 2019. Tests were carried out in patients with cancers without standard treatment or when patients had already undergone standard treatment. Data from DNA and RNA panels were analyzed in 198 and 191 patients, respectively. The percentage of patients who were given therapeutic or diagnostic recommendations was 61% (120/198). One hundred and four samples (53%) harbored gene alterations that were detected with the DNA panel and had potential treatment implications, and 14 samples (7%) had a high tumor mutational burden. Twenty‐two samples (11.1%) harbored 30 fusion transcripts or MET exon 14 skipping that were detected by the RNA panel. Of those 30 transcripts, 6 had treatment implications and 4 had diagnostic implications. Thirteen patients (7%) were found to have pathogenic or likely pathogenic germline variants and genetic counseling was recommended. Overall, 12 patients (6%) received recommended treatment. In summary, patients benefited from both TOP DNA and RNA panels while following the same indication as the approved CGP tests. (UMIN000033647).
Genetic variations predicting progression with docetaxel and novel androgen‐receptor pathway inhibitors
Authors: Shiota Masaki , Akamatsu Shusuke , Sekine Yuya , Kimura Hiroko , Narita Shintaro , Fujimoto Naohiro , Terada Naoki , Blas Leandro , Habuchi Tomonori , Kamoto Toshiyuki , Momozawa Yukihide , Eto Masatoshi
Published: January 2023

Genetic variations represented by single‐nucleotide polymorphisms (SNPs) could be helpful for choosing an effective treatment for patients with prostate cancer. This study investigated the prognostic and predictive values of SNPs associated with the prognoses of pharmacotherapy for prostate cancer through their pharmacological mechanisms. Patients treated with docetaxel or androgen receptor pathway inhibitors (ARPIs), such as abiraterone and enzalutamide, for castration‐resistant prostate cancer were included. The SNPs of interest were genotyped for target regions. The prognostic and predictive values of the SNPs for time to progression (TTP) were examined using the Cox hazard proportional model and interaction test, respectively. Rs1045642 in ABCB1, rs1047303 in HSD3B1, rs1856888 in HSD3B1, rs523349 in SRD5A2, and rs34550074 in SLCO2A1 were differentially associated with TTP between docetaxel chemotherapy and ARPI treatment. In addition to rs4775936 in CYP19A1, rs1128503 in ABCB1 and rs1077858 in SLCO2B1 might be differentially associated with TTP between abiraterone and enzalutamide treatments. Genetic predictive models using these SNPs showed a differential prognosis for treatments. This study identified SNPs that could predict progression as well as genetic models that could predict progression when patients were treated with docetaxel versus ARPI and abiraterone versus enzalutamide. The use of genetic predictive models is expected to be beneficial in selecting the appropriate treatment for the individual patient.
The influence of periodontitis case definition on the association between periodontal disease and glycaemic status
Authors: Alhassani Ahmed A.
Published: January 2023

Objective

The association between periodontitis and glycaemic control is complex, and often described as ‘bidirectional’. Although epidemiological studies have examined this relationship extensively, a disagreement on periodontitis case definition still exists. This study aimed to assess the influence of case definition on the association between periodontal disease and glycaemic status.

Methods

The study is a secondary analysis of data from the United States National Health and Nutrition Examination Survey (NHANES), 2009–2014 cycles. The association between periodontitis and glycated haemoglobin (HbA1c) was assessed using different periodontitis case definitions: the definition by the Centers for Disease Control and Prevention and the American Academy of Periodontology (CDC/AAP), Community Periodontal Index (CPI), ≥1 site with ≥3 mm clinical attachment loss (CAL) and ≥4 mm probing depth (PD), ≥1 site with ≥4 mm CAL and ≥4 mm PD, the 5th European Workshop definitions, Machtei et al. ‘established periodontitis’, the 2017 World Workshop classification, and self‐reported periodontitis. The associations between periodontitis and HbA1c were compared across the case definitions.

Results

There was substantial variability in prevalence estimates of periodontitis, and in the strength of association between periodontitis and HbA1c when different case definitions were applied. The CDC/AAP and stage III/IV periodontitis were consistently significantly associated with elevated HbA1c. For stage III/IV, the adjusted odds ratios of prediabetes and diabetes HbA1c were 1.19 and 1.76, respectively.

Conclusion

Comprehensive periodontitis case definitions that account for CAL and PD, such as the CDC/AAP and the 2017 classification, seem to better detect the association between periodontal disease and HbA1c.
Natural history of nonfunctioning pituitary macroadenomas followed without intervention: A retrospective cohort study
Authors: Ayalon‐Dangur Irit , Robenshtok Eyal , Duskin‐Bitan Hadar , Tsvetov Gloria , Gorshtein Alex , Akirov Amit , Shimon Ilan
Published: January 2023

Objective

The treatment strategy for nonfunctioning pituitary adenomas (NFPA) includes surgery, radiotherapy, medical treatment, or follow‐up. Prior series of patients with NFPAs followed without intervention include small numbers of patients with macroadenomas. This study investigated the natural history of patients with macroadenomas followed without treatment.

Design and patients

Retrospective cohort study included patients>18 years, with a diagnosis of NFPA ≥ 10 mm who were naïve to surgery or medical treatment and followed more than 12 months after diagnosis. Patients with chiasmal threat were excluded. Follow‐up terminated if the patient underwent surgery, received cabergoline or was lost to follow‐up.

Measurements

Data collected included evaluation of tumour characteristics and size by MRI, symptoms including visual disturbances, and hormonal levels. Tumour growth was defined as maximal diameter increase of ≥2 mm.

Results

The cohort included 49 patients (30 males, mean age 68.0 ± 12.0 years). At diagnosis, the average tumour size was 17.8 ± 5.9 mm. Mean follow‐up time was 4.9 ± 4.9 years. Increase in tumour size occurred in 16 patients (33%), with an average growth of 5.1 ± 4.4 mm. Reduction in tumour size occurred in 10 patients (20%), with a mean decrease of 3.5 ± 1.3 mm. Twenty‐three patients remained with stable tumours. Overall, 33 patients (67%) were observed without any intervention; 3 patients were operated and 13 were treated with cabergoline. None of the parameters including age, gender, baseline tumour size, invasiveness, visual disturbances, or hypopituitarism at diagnosis, predicted tumour growth.

Conclusion

Observation of NFPAs without surgery or medical therapy is a reasonable approach in selected patients. In our study, no parameter predicted tumour growth.
When the microbiome helps the brain‐current evidence
Authors: Drljača Jovana , Milošević Nataša , Milanović Maja , Abenavoli Ludovico , Milić Nataša
Published: January 2023

The gut microbiota‐brain axis has been recognized as a network of connections that provides communication between the gut microflora and both central and autonomic nervous system. The gut microbiota alteration has been targeted for therapy in various neurodegenerative and psychiatric disbalances. Psychobiotics are probiotics that contribute beneficially to the brain function and the host mental health as a result of an interaction with the commensal gut bacteria, although their mechanism of action has not been completely revealed. In this state‐of‐art review, the findings about the potential therapeutic effects of the psychobiotics alone or in combination with conventional medicine in the treatment of neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, as well as in some psychiatric diseases like depression, schizophrenia, and bipolar disorder, have been summarized. The evidence of the psychobiotics therapeutic outcomes obtained in preclinical and clinical trials have been given respectively for the observed neurodegenerative and psychiatric disorders.
Hydroxychloroquine for treatment of non‐hospitalized adults with COVID‐19: A meta‐analysis of individual participant data of randomized trials
Authors: Mitjà Oriol , Reis Gilmar , Boulware David R. , Spivak Adam M. , Sarwar Ammar , Johnston Christine , Webb Brandon , Hill Michael D. , Smith Davey , Kremsner Peter , Curran Marla , Carter David , Alexander Jim , Corbacho Marc , Lee Todd C. , Hullsiek Katherine Huppler , McDonald Emily G. , Hess Rachel , Hughes Michael , Baeten Jared M. , Schwartz Ilan , Metz Luanne , Richer Lawrence , Chew Kara W. , Daar Eric , Wohl David , Dunne Michael
Published: January 2023

Hydroxychloroquine (HCQ) was initially promoted as an oral therapy for early treatment of coronavirus disease 2019 (COVID‐19). Conventional meta‐analyses cannot fully address the heterogeneity of different designs and outcomes of randomized controlled trials (RCTs) assessing the efficacy of HCQ in outpatients with mild COVID‐19. We conducted a pooled analysis of individual participant data from RCTs that evaluated the effect of HCQ on hospitalization and viral load reduction in outpatients with confirmed COVID‐19. We evaluated the overall treatment group effect by log‐likelihood ratio test (−2LL) from a generalized linear mixed model to accommodate correlated longitudinal binary data. The analysis included data from 11 RCTs. The outcome of virological effect, assessed in 1560 participants (N = 795 HCQ, N = 765 control), did not differ significantly between the two treatment groups (−2LL = 7.66; p = 0.18) when adjusting for cohort, duration of symptoms, and comorbidities. The decline in polymerase chain reaction positive tests from day 1 to 7 was 42.0 and 41.6 percentage points in the HCQ and control groups, respectively. Among the 2037 participants evaluable for hospitalization (N = 1058 HCQ, N = 979 control), we found no significant differences in hospitalization rate between participants receiving HCQ and controls (odds ratio 0.995; 95% confidence interval 0.614–1.610; −2LL = 0.0; p = 0.98) when adjusting for cohort, duration of symptoms, and comorbidities. This individual participant data meta‐analysis of 11 HCQ trials that evaluated severe acute respiratory syndrome‐coronavirus 2 viral clearance and COVID‐19 hospitalization did not show a clinical benefit of HCQ. Our meta‐analysis provides evidence to support the interruption in the use of HCQ in mild COVID‐19 outpatients to reduce progression to severe disease.
Concomitant nivolumab‐associated Grover disease and bullous pemphigoid in a patient with metastatic renal cell carcinoma
Authors: Khazaeli Mahyar , Grover Raminder , Pei Susan
Published: January 2023

Immune checkpoint inhibitor (ICI)‐induced bullous pemphigoid (BP) and Grover disease (GD) are uncommon, and concomitant GD and BP is rarer still. We report a third case of concomitant BP and GD associated with nivolumab with emphasis on the clinical, histopathologic and immunofluorescence findings as well as differential diagnoses. A 73‐year‐old male with metastatic renal cell carcinoma on nivolumab developed erythematous scaly papules on the trunk with biopsy showing suprabasal acantholysis with dyskeratosis, consistent with GD. Subsequently, he developed widespread lesions on arms, legs, trunk, and scrotum with new vesiculobullae and urticarial lesions. Biopsy of a vesicle showed subepidermal blister with numerous eosinophils and neutrophils, and immunofluorescence and serological studies were supportive of BP. He continued to have clinically apparent GD that was confirmed on repeat biopsy. The patient was diagnosed with concomitant GD and BP induced by nivolumab and successfully treated with dupilumab. The relationship between ICI‐induced GD and BP is not well understood; it has been suggested that T‐cell activation against the BP180 antigen expressed on surface of tumor cells may predispose susceptible individuals to BP. Subsequent ICI‐induced GD may create keratinocyte injury needed to expose additional proteins to reactivated and autoreactive T‐cells, leading to autoimmunity. An important differential diagnosis is bullous GD, which can be distinguished by negative immunofluorescence and serological studies.
Beyond the Genome: Genetically Modified Crops in Africa and the Implications for Genome Editing
Authors: Rock Joeva Sean , Schnurr Matthew A. , Kingiri Ann , Glover Dominic , Stone Glenn Davis , Ely Adrian , Fischer Klara
Published: January 2023

Genome editing — a plant‐breeding technology that facilitates the manipulation of genetic traits within living organisms — has captured the imagination of scholars and professionals working on agricultural development in Africa. Echoing the arrival of genetically modified (GM) crops decades ago, genome editing is being heralded as a technology with the potential to revolutionize breeding based on enhanced precision, reduced cost and increased speed. This article makes two interventions. First, it identifies the discursive continuity linking genome editing and the earlier technology of genetic modification. Second, it offers a suite of recommendations regarding how lessons learned from GM crops might be integrated into future breeding programmes focused on genome editing. Ultimately, the authors argue that donors, policy makers and scientists should move beyond the genome towards systems‐level thinking by prioritizing the co‐development of technologies with farmers; using plant material that is unencumbered by intellectual property restrictions and therefore accessible to resource‐poor farmers; and acknowledging that seeds are components of complex and dynamic agroecological production systems. If these lessons are not heeded, genome‐editing projects are in danger of repeating mistakes of the past.