bluuebunny/crossref_metadata_2025 huggingface dataset:
Color morphs of the fire salamander are discriminated at night by conspecifics and predators
Authors: Aguilar P. , Pérez i de Lanuza G. , Martínez‐Gil H. , Dajčman U. , Simčič T. , Pinho C. , Žagar A. , Megía‐Palma R.
Published: November 2023

The coexistence of multiple discrete color phenotypes (i.e. color polymorphism) has been studied in many diurnal species where environmental light allows most visual systems to chromatically discriminate color morphs. However, there is a large gap in our understanding of the discrimination thresholds and the function color polymorphisms play at night. We collected spectral data from the throats of red‐ and yellow‐morph males in a polymorphic population of the nocturnal amphibian Salamandra salamandra gallaica. We estimated the discriminability between morphs and their conspicuousness at night by fitting visual models of conspecifics and predators. We also collected morphological, behavioral and physiological data and assessed the abundance and activity patterns of each morph to explore their potential function. Visual models indicated that both conspecifics and predators can visually discriminate salamander color morphs under night‐light conditions. Assuming the potential role of yellow and red color patches as visual signals, putatively related to social signaling, we could suspect that these colors represent different adaptive optima. Red‐morph individuals had shorter bodies and lower body condition, but both morphs showed similar space use. In addition, both color morphs exhibited similar metabolic physiology, suggesting that the observed similarity in these traits may be better explained by the shared environmental conditions, rather than color. Finally, differences in the conspicuousness of red and yellow morphs could result in differential predation pressure.
Spatially segregated defects and IGF1‐responsiveness of hilar and peripheral biliary organoids from a model of Alagille syndrome
Authors: Iqbal Afshan , Van Hul Noemi , Belicova Lenka , Corbat Agustin A. , Hankeova Simona , Andersson Emma R.
Published: November 2023

Background & Aims

Alagille syndrome (ALGS) manifests with peripheral intrahepatic bile duct (IHBD) paucity, which can spontaneously resolve. In a model for ALGS, Jag1Ndr/Ndr mice, this occurs with distinct architectural mechanisms in hilar and peripheral IHBDs. Here, we investigated region‐specific IHBD characteristics and addressed whether IGF1, a cholangiocyte mitogen that is downregulated in ALGS and in Jag1Ndr/Ndr mice, can improve biliary outcomes.

Methods

Intrahepatic cholangiocyte organoids (ICOs) were derived from hilar and peripheral adult Jag1+/+ and Jag1Ndr/Ndr livers (hICOs and pICOs, respectively). ICOs were grown in Matrigel or microwell arrays, and characterized using bulk RNA sequencing, immunofluorescence, and high throughput analyses of nuclear sizes. ICOs were treated with IGF1, followed by analyses of growth, proliferation, and death. CellProfiler and Python scripts were custom written for image analyses. Key results were validated in vivo by immunostaining.

Results

Cell growth assays and transcriptomics demonstrated that Jag1Ndr/Ndr ICOs were less proliferative than Jag1+/+ ICOs. IGF1 specifically rescued survival and growth of Jag1Ndr/Ndr pICOs. Jag1Ndr/Ndr hICOs were the least proliferative, with lower Notch signalling and an enrichment of hepatocyte signatures and IGF uptake/transport pathways. In vitro (Jag1Ndr/Ndr hICOs) and in vivo (Jag1Ndr/Ndr hilar portal tracts) analyses revealed ectopic HNF4a+ hepatocytes.

Conclusions

Hilar and peripheral Jag1Ndr/Ndr ICOs exhibit differences in Notch signalling status, proliferation, and cholangiocyte commitment which may result in cholangiocyte‐to‐hepatocyte transdifferentiation. While Jag1Ndr/Ndr pICOs can be rescued by IGF1, hICOs are unresponsive, perhaps due to their hepatocyte‐like state and/or expression of IGF transport components. IGF1 represents a potential therapeutic for peripheral bile ducts.
Object detection: A novel AI technology for the diagnosis of hepatocyte ballooning
Authors: Zheng Tian‐Lei , Sha Jun‐Cheng , Deng Qian , Geng Shi , Xiao Shu‐Yuan , Yang Wen‐Jun , Byrne Christopher D. , Targher Giovanni , Li Yang‐Yang , Wang Xiang‐Xue , Wu Di , Zheng Ming‐Hua
Published: November 2023

Metabolic dysfunction‐associated fatty liver disease (MAFLD) has reached epidemic proportions worldwide and is the most frequent cause of chronic liver disease in developed countries. Within the spectrum of liver disease in MAFLD, steatohepatitis is a progressive form of liver disease and hepatocyte ballooning (HB) is a cardinal pathological feature of steatohepatitis. The accurate and reproducible diagnosis of HB is therefore critical for the early detection and treatment of steatohepatitis. Currently, a diagnosis of HB relies on pathological examination by expert pathologists, which may be a time‐consuming and subjective process. Hence, there has been interest in developing automated methods for diagnosing HB. This narrative review briefly discusses the development of artificial intelligence (AI) technology for diagnosing fatty liver disease pathology over the last 30 years and provides an overview of the current research status of AI algorithms for the identification of HB, including published articles on traditional machine learning algorithms and deep learning algorithms. This narrative review also provides a summary of object detection algorithms, including the principles, historical developments, and applications in the medical image analysis. The potential benefits of object detection algorithms for HB diagnosis (specifically those combined with a transformer architecture) are discussed, along with the future directions of object detection algorithms in HB diagnosis and the potential applications of generative AI on transformer architecture in this field. In conclusion, object detection algorithms have huge potential for the identification of HB and could make the diagnosis of MAFLD more accurate and efficient in the near future.
Earning Their Stripes? How Political Experience Shapes Gendered Policy Prioritization
Authors: Hargrave Lotte
Published: November 2023

How does political experience affect the issues that men and women politicians prioritize? Gender stereotypical expectations dictate that women focus more on traditionally “feminine” policy areas. While past findings broadly support this, they do not examine how policy priorities shift with increased experience. Focusing on the United Kingdom, I argue that gender differences in the extent to which politicians raise issues traditionally associated with women will be most pronounced among junior politicians who lack experience in the eyes of the public and their colleagues, but will decline with increased political experience. To test this, I study parliamentary debates between 1997 and 2019 and leverage novel quantitative text approaches to measure politicians' issue priorities. I show that, among junior politicians, women talk significantly more about “feminine” issues, however this gap decreases markedly with increased seniority. These findings have important implications for the representation of women's voices and perspectives within the policymaking process.
Secrets of getting started: Regulation of the first committed step of peptidoglycan synthesis by protein phosphorylation in Enterococcus and other Gram‐positive bacteria
Authors: Winkler Malcolm E. , Joseph Merrin , Tsui Ho‐Ching T.
Published: November 2023

Regulation of the first committed step of peptidoglycan precursor synthesis by MurA‐enzyme homologs has recently taken center stage in many different bacteria. In different low‐GC Gram‐positive bacteria, regulation of this step has been shown to be regulated by phosphorylation of homologs of the IreB/ReoM regulatory protein by PASTA‐domain Ser/Thr‐protein kinases. In this issue, Mascari, Little, and Kristich determine this regulatory pathway and its links to resistance to cephalosporin β‐lactam antibiotics in the major human pathogen, Enterococcus faecalis (Efa). Unbiased genetic selections identified MurAA (MurA‐family homolog) as the downstream target of IreB regulation in the absence of the IreK Ser/Thr‐protein kinase. Physiological and biochemical approaches, including determination of MICs to ceftriaxone, Western blotting of MurAA cellular amounts, isotope incorporation into peptidoglycan sacculi, and thermal‐shift binding assays of purified proteins, demonstrated that unphosphorylated IreB, together with proteins MurAB (MurZ‐family homolog), and ReoY(Efa) negatively regulate MurAA stability and cellular amount by the ClpCP protease. Importantly, this paper supports the idea that ceftriaxone stimulates phosphorylation of IreB, which leads to increased cellular MurAA amount and precursor pathway flux required for E. faecalis cephalosporin resistance. Overall, findings in this paper significantly contribute to understanding variations of this central regulatory pathway in other low‐GC Gram‐positive bacteria.
Esophageal anatomy and physiology vary across spastic and non‐spastic phenotypes of disorders of esophagogastric junction outflow
Authors: Vahedi Farnoosh , Low Eric E. , Kaizer Alexander M. , Fehmi Syed Abbas , Hasan Aws , Chang Michael A. , Kwong Wilson , Krinsky Mary L. , Anand Gobind , Greytak Madeline , Yadlapati Rena
Published: November 2023

Background

Pathophysiologic mechanisms of disorders of esophagogastric junction (EGJ) outflow are poorly understood. We aimed to compare anatomic and physiologic characteristics among patients with disorders of EGJ outflow and normal motility.

Methods

We retrospectively evaluated adult patients with achalasia types 1, 2, 3, EGJ outflow obstruction (EGJOO) or normal motility on high‐resolution manometry who underwent endoscopic ultrasound (EUS) from January 2019 to August 2022. Thickened circular muscle was defined as ≥1.6 mm. Characteristics from barium esophagram (BE) and functional lumen imaging probe (FLIP) were additionally assessed.

Key Results

Of 71 patients (mean age 56.2 years; 49% male), there were 8 (11%) normal motility, 58 (82%) had achalasia (5 (7%) type 1, 32 (45%) classic type 2, 21 (30%) type 3 [including 12 type 2 with FEPs]), and 7 (7%) had EGJOO. A significantly greater proportion of type 3 achalasia had thickened distal circular muscle (76.2%) versus normal motility (0%; p < 0.001) or type 2 achalasia (25%; p < 0.001). Type 1 achalasia had significantly wider mean maximum esophageal diameter on BE (57.8 mm) compared to type 2 achalasia (32.8 mm), type 3 achalasia (23.4 mm), EGJOO (15.9 mm), and normal motility (13.5 mm). 100% type 3 achalasia versus 0% type 1 achalasia/normal motility had tertiary contractions on BE. Mean EGJ distensibility index on FLIP was lower for type 3 achalasia (1.2 mmHg/mm2) and EGJOO (1.2 mmHg/mm2) versus type 2 (2.3 mmHg/mm2) and type 1 achalasia (2.9 mmHg/mm2).

Conclusions

Our findings suggest distinct pathologic pathways may exist: type 3 achalasia and EGJOO may represent a spastic outflow phenotype consisting of a thickened, spastic circular muscle, which is distinct from type 1 and 2 achalasia consisting of a thin caliber circular muscle layer with more prominent esophageal dilation.
ZBTB20 mediates stress‐induced visceral hypersensitivity via activating the NF‐κB/transient receptor potential channel pathway
Authors: Luo Qing‐Qing , Cheng Li , Wang Bo , Chen Xin , Li Wen‐Ting , Chen Sheng‐Liang
Published: November 2023

Background

Psychological stress is a major trigger for visceral hypersensitivity (VH) in irritable bowel syndrome. The zinc finger protein ZBTB20 (ZBTB20) is implicated in somatic nociception via modulating transient receptor potential (TRP) channels, but its role in the development of VH is unclear. This study aimed to investigate the role of ZBTB20/TRP channel axis in stress‐induced VH.

Methods

Rats were subjected to water avoidance stress (WAS) for 10 consecutive days. Small interfering RNA (siRNA) targeting ZBTB20 was intrathecally administered. Inhibitors of TRP channels, stress hormone receptors, and nuclear factor kappa‐B (NF‐κB) were administered. Visceromotor response to colorectal distension was recorded. Dorsal root ganglia (DRGs) were dissected for Western blot, coimmunoprecipitation, and chromatin immunoprecipitation. The DRG‐derived neuron cell line was applied for specific research.

Key Results

WAS‐induced VH was suppressed by the inhibitor of TRPV1, TRPA1, or TRPM8, with enhanced expression of these channels in L6‐S2 DRGs. The inhibitor of glucocorticoid receptor or β2‐adrenergic receptor counteracted WAS‐induced VH and TRP channel expression. Concurrently, WAS‐induced stress hormone‐dependent ZBTB20 expression and NF‐κB activation in DRGs. Intrathecally injected ZBTB20 siRNA or an NF‐κB inhibitor repressed WAS‐caused effect. In cultured DRG‐derived neurons, stress hormones promoted nuclear translocation of ZBTB20, which preceded p65 nuclear translocation. And, ZBTB20 siRNA suppressed stress hormone‐caused NF‐κB activation. Finally, WAS enhanced p65 binding to the promoter of TRPV1, TRPA1, or TRPM8 in rat DRGs.

Conclusions and Inferences

ZBTB20 mediates stress‐induced VH via activating NF‐κB/TRP channel pathway in nociceptive sensory neurons.
Nonbinary fungal signals and calcium‐mediated transduction in plant immunity and symbiosis
Authors: Giovannetti Marco , Binci Filippo , Navazio Lorella , Genre Andrea
Published: November 2023

Chitin oligomers (COs) are among the most common and active fungal elicitors of plant responses. Short‐chain COs from symbiotic arbuscular mycorrhizal fungi activate accommodation responses in the host root, while long‐chain COs from pathogenic fungi are acknowledged to trigger defence responses. The modulation of intracellular calcium concentration – a common second messenger in a wide variety of plant signal transduction processes – plays a central role in both signalling pathways with distinct signature features. Nevertheless, mounting evidence suggests that plant immunity and symbiosis signalling partially overlap at multiple levels. Here, we elaborate on recent findings on this topic, highlighting the nonbinary nature of chitin‐based fungal signals, their perception and their interpretation through Ca2+‐mediated intracellular signals. Based on this, we propose that plant perception of symbiotic and pathogenic fungi is less clear‐cut than previously described and involves a more complex scenario in which partially overlapping and blurred signalling mechanisms act upstream of the unambiguous regulation of gene expression driving accommodation or defence responses.
Tensile forces in the neurovascular bundle: A contributor to orthodontic relapse?
Authors: Oki Dayton S. , Yamakawa Karyl‐Lin M. , Paranjapye Natasha A. , Meza Lucas R. , Wong Chester , Patel Zainab , Bollinger Jacqueline , Huang Greg J.
Published: November 2023

Objectives

The aim of this study is to investigate the neurovascular bundle (NVB) as a potential orthodontic relapse factor. The mechanical properties and the forces generated in the NVB after orthodontic extrusion are explored.

Materials and Methods

Six NVBs branching from the inferior alveolar nerve to the apices of the mandibular canines and premolars of mature pigs were harvested. Stress relaxation tests were conducted. A standard linear solid model (SLS) was utilized to simulate the orthodontic extrusion of a single rooted tooth with NVB length and cross‐sectional diameter of 3.6 and 0.5 mm, respectively, so the NVB was stretched 10% and 20% of its original length. The maximum force within the NVB was then calculated.

Results

Based on our data, the average Young's modulus before relaxation (), after relaxation () and the difference between Young's moduli before and after relaxation () were 324 ± 123, 173 ± 73 and 151 ± 52 kPa, respectively. The theoretical force within the NVB stretched to 10% and 20% strain was 3 and 5 mN, respectively.

Conclusion

The data from our study indicate that the NVB exhibits stress relaxation, a characteristic trait of viscoelastic materials. SLS model simulation predicted residual forces around 5 mN for elongation up to 20%. We observed strain hardening with additional elongation, which has the potential to cause forces to increase exponentially. Therefore, tensile forces in the NVB should not be ruled out as a contributor to orthodontic relapse, especially in adult patients who may have decreased adaptability of their NVB. Further preclinical and clinical models should be developed to further clarify what is the contribution of the NVB to orthodontic relapse.
Maternal factors in the origin of cleft lip/cleft palate: A population‐based case–control study
Authors: Ács Lili , Nemes Bálint , Nagy Krisztián , Ács Márton , Bánhidy Ferenc , Rózsa Noémi
Published: November 2023

Objectives

Orofacial clefts are among the most common birth defects, with an estimated worldwide incidence of around 1.5‐1.7 per 1000 live‐born babies. The most frequent form of orofacial clefts is cleft lip with or without cleft palate (CL ± CP). The role of environmental factors in the development of clefts is unclear in most patients, thus the aim of this study was to estimate possible maternal risk factors in the origin of CL ± CP.

Materials and Methods

1648 CL ± CP cases, 2654 matched controls and 57 231 population controls were evaluated from The Hungarian Case–Control Surveillance of Congenital Abnormalities. Maternal factors during the critical period in cases and controls were compared. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were estimated in a multivariable conditional logistic regression model.

Results

Among socio‐demographic data, we have found significant differences between maternal employment. The proportion of unskilled mothers (6.5%) were higher in the CL ± CP group than in controls (3.5%). Medically recorded maternal anaemia, excessive vomiting and threatened abortion were associated with a higher risk of CL ± CP. An elevated risk was also found in various acute illnesses such as influenza (OR: 2.4, 95% CI: 3.0‐5.8), acute bronchitis (OR: 4.5, 95% CI: 1.6‐12.6) and urinary tract infections (OR: 3.5, 95% CI: 2.0‐6.0). Maternal migraine and essential hypertension occurred more frequently in the mothers of cases than in controls.

Conclusion

The findings of this study suggest that maternal diseases and lifestyle factors during the first trimester play a significant role in the development of CL ± CP.
TGF‐β1 Inhibits Osteoclast Differentiation and Abnormal Angiogenesis in Intervertebral Disc Degeneration: Evidence from RNA Sequencing and Animal Studies
Authors: Wang Keping , Wu Zuolong , Gong Chaoyang , Zhao Guanghai , Zhang Haihong
Published: November 2023

Objective

Mechanisms involved in developing intervertebral disc degeneration (IDD) are poorly understood, thus making developing effective therapies difficult. This study aimed to suggest a possible molecular mechanism, based on transcriptome sequencing‐identified transforming growth factor (TGF‐β), underlying the effects on bone homeostasis in IDD.

Methods

A mouse model for IDD was established. Transcriptome sequencing of nucleus pulposus tissue from mice (n = 3) identified differentially expressed mRNAs and key genes impacting bone homeostasis. A protein–protein interaction network pinpointed core genes. GO and KEGG analysis revealed gene functions. Expression levels of TGF‐β1, tartrate‐resistant acid phosphatase (TRAP), and cathepsin K (CTSK) were measured. Micro‐CT evaluated vertebral structures and vascular imaging. Western Blot measured expression levels of Vegf, Opn, MMP3, and MMP13. Safranin O‐Fast Green and TRAP staining were performed on intervertebral discs and endplates.

Results

Transcriptomic analysis found 1790 differentially expressed mRNAs in IDD mice. Twenty‐eight genes related to bone homeostasis in IDD were identified. TGF‐β1 was confirmed as the core gene. GO and KEGG showed TGF‐β1 regulates osteoclast markers like CTSK and TRAP through pathways including NF‐κB and MAPK. Experimental validation revealed lower TGF‐β1 expression in IDD mice than controls, and increased TRAP and CTSK expression. Micro‐CT showed decreased bone mass and intervertebral disc space in IDD mice. Vascular imaging showed increased vascular volume in IDD cartilaginous endplates. Western blot displayed increased VEGF and OPN levels, but decreased MMP3 and MMP13 in IDD mice. Safranin O‐fast green staining revealed severe IDD degeneration. However, TGF‐β1 injection improved bone parameters in IDD mice. In vitro experiments confirmed TGF‐β1 inhibits bone marrow macrophages differentiation into osteoclasts.

Conclusion

From our data, we conclude that TGF‐β1 repressed osteoclast differentiation and aberrant bone‐associated angiogenesis in cartilage endplates (EPs) to alleviate IDD, which may be instrumental for the therapeutic targeting of IDD.
Postoperative Prevalence and Risk Factors for Serum Hypokalemia in Patients with Primary Total Joint Arthroplasty
Authors: Pan Pin , Zhang Zitao , Zhang Xiaofeng , Jiang Qing , Xu Zhihong
Published: November 2023

Objective

Regular monitoring of serum potassium after a total joint arthroplasty (TJA) is a form of routine examination that can help detect abnormal serum potassium levels and reduce the incidences of adverse events that may occur on account of postoperative hypokalemia. Previous studies rarely discussed hypokalemia after joint replacement. In the present study, our primary goal was to investigate the incidence and possible risk factors of hypokalemia after a total hip and knee replacement procedure was performed.

Methods

This study included patients who underwent a unilateral total knee or hip arthroplasty in our department between April 2017 and March 2018. Serum potassium levels pre and post operation were collected and retrospectively analyzed. The differences in age, gender, body mass index (BMI), history of diseases, red blood cell (RBC), hemoglobin, hematocrit, glomerular filtration rate, ejection fraction, blood glucose, urine creatinine, urea nitrogen, intraoperative blood loss, operation time, drainage, preoperative potassium, surgery type, were compared between those patients diagnosed with hypokalemia and their non‐hypokalemia at different times post surgery. Thereafter, the risk factors of postoperative hypokalemia patients were analyzed using statistical procedure multiple logistic regression model.

Results

The risk of hypokalemia after TJA was 53.1%, while, that on the first, third, and fifth day after operation was 12.5%, 40.7%, and 9.6% respectively. The serum potassium level on the first, third, and fifth postoperative days was 3.84 ± 0.32, 3.59 ± 0.34, and 3.80 ± 0.32 mmol/l, respectively. However, the level on the third day appeared to be the lowest (p = 0.015) of them all. The independent risk factors for hypokalemia after a total hip and knee replacement were the level of preoperative serum potassium concentration (p = 0.011), preoperative red blood cells counts (p = 0.027), and history of diabetes (p = 0.007).

Conclusion

Regular monitoring of serum potassium concentration should be performed post TJA. We need to pay more attention to the patient's preoperative potassium levels along with their red blood cell counts especially in patients diagnosed with type 2 diabetes mellitus.
A Novel Multiple Screw Distraction Reducer System in the Treatment of Scoliosis with a Severe Rib Hump
Authors: Deng Zhipeng , Wang Liang , Liu Limin , Wang Lei , Yang Xi , Song Yueming
Published: November 2023

Objectives

The treatment of scoliosis with a severe rib hump remains a major challenge. Traditional vertebral rotation techniques are not satisfactory, and thoracoplasty has many pulmonary complications that limit its application. A novel surgical device, the multiple screw distraction reducer (MSDR) system, provides longitudinal distraction during the corrective operation while at the same time providing lateral translation and axial derotation, which may facilitate the correction of a rib hump. This study was performed to investigate the effectiveness of the MSDR system for adolescent idiopathic scoliosis (AIS) with a severe rib hump.

Methods

This was a case‐matched study of patients with retrospectively collected data from our hospital between January 2017 and December 2021. Sixty‐eight patients who underwent one‐stage posterior pedicle screw‐instrumented spinal fusion were matched by the Cobb angle of the main curve and rib hump. All patients underwent a minimum of 2 years of follow‐up. The patients were divided into two groups: the MSDR group (using the MSDR system, n = 34) and the DVR group (using direct vertebral derotation, n = 34). The patients were evaluated for the height of the rib hump, deformity correction, complications, and SRS‐30 scores. The unpaired Student's t‐test and Pearson's χ2‐test were used to compare the outcome measures between the two groups. Multiple linear regression analysis was used to examine the variables that affected the correction of a rib hump.

Results

The rib hump was 30.21 ± 6.21 mm versus 29.35 ± 6.52 mm (p = 0.583) preoperatively and 9.18 ± 4.06 mm versus 13.82 ± 5.54 mm (p < 0.001) at the last follow‐up in the MSDR and DVR groups, respectively. The correction rates were 70.83% and 53.56%, respectively (p < 0.001). Preoperatively, the main thoracic curve was 58.43° ± 7.97° and 57.84° ± 6.32° (p = 0.736) and was corrected to 10.92° ± 5.47° and 19.14° ± 5.32° (p < 0.001) at last follow‐up in the MSDR and DVR group, respectively. Thoracic kyphosis was restored from 18.24° ± 5.19° and 17.98° ± 5.28° (p = 0.836) in the MSDR and DVR group to 24.59° ± 4.41° and 19.32° ± 4.96° (p < 0.001), respectively. Correction of apical vertebra rotation and translation in the main thoracic curve were significantly better in the MSDR group than in the DVR group (p < 0.05). There was no significant difference in the Lenke type, implant density, estimated blood loss, or follow‐up duration between the two groups, whereas the operation time in the DVR group was significantly less than that in the MSDR group. There were only two minor pulmonary complications in the MSDR group. At the last follow‐up, the MSDR group scored higher in terms of appearance and satisfaction (p < 0.05).

Conclusion

The MSDR system, enabling better coronal alignment, thoracic kyphosis, and axial derotation, could be a safe and effective technique for severe rib hump correction in AIS.
Effect of SGLT2 inhibitors on cardiovascular events in patients with atrial fibrillation: A systematic review and meta‐analysis of randomized controlled trials
Authors: Zheng Shiyue , Lai Yiwei , Jiang Chao , He Liu , Zhao Zixu , Li Wenjie , Tang Ribo , Sang Caihua , Long Deyong , Du Xin , Ma Changsheng , Dong Jianzeng
Published: November 2023

Background

Sodium‐glucose cotransporter 2 inhibitors (SGLT2i) is reported to reduce incident atrial fibrillation (AF) in patients with or without diabetes; however, its cardiovascular (CV) benefit for AF patients remains unclear.SS

Aims

To investigate the effect of SGLT2i on the incidence of CV events in patients with AF.

Methods

Six randomized controlled trials (RCTs) assessing the effects of SGLT2i on CV outcomes in patients with or without AF were included (PROSPERO: CRD 42023431535). The primary endpoint was the composite outcome of heart failure (HF) hospitalization and CV death. Additionally, we assessed the effects of treatment in prespecified subgroups on HF hospitalization, CV death, and all‐cause mortality.

Results

Among 38,529 participants from all trials, 5018 patients with AF were treated with SGLT2i. The follow‐up period of these trials ranged from 2.3 to 3.3 years. SGLT2i treatment was significantly associated with the risk reduction of primary endpoint in patients with AF (risk ratio [RR] 0.81, 95% confidence interval [CI] 0.74–0.88; p < 0.001), consistent with the finding in the general population (p for interaction = 0.76). SGLT2i was also associated with a consistent reduction in the risk of HF hospitalization in patients with AF (RR 0.76, 95% CI 0.69–0.84; p < 0.001) or not (RR 0.72, 95% CI 0.64–0.80; p < 0.0001), with no statistical difference between them (p for interaction = 0.41). Meta‐regression further revealed no significant association between the prevalence of HF with reduced ejection fraction or diabetes and the effect size of SGLT2i.

Conclusions

The treatment effects of SGLT2i were associated with a lower incidence of CV events, especially HF hospitalization, in patients with AF.
Unveiling the potential of machine learning in schizophrenia diagnosis: A meta‐analytic study of task‐based neuroimaging data
Authors: Wang Xuan , Yan Chao , Yang Peng‐yuan , Xia Zheng , Cai Xin‐lu , Wang Yi , Kwok Sze Chai , Chan Raymond C.K.
Published: November 2023

The emergence of machine learning (ML) techniques has opened up new avenues for identifying biomarkers associated with schizophrenia (SCZ) using task‐related fMRI (t‐fMRI) designs. To evaluate the effectiveness of this approach, we conducted a comprehensive meta‐analysis of 31 t‐fMRI studies using a bivariate model. Our findings revealed a high overall sensitivity of 0.83 and specificity of 0.82 for t‐fMRI studies. Notably, neuropsychological domains modulated the classification performance, with selective attention demonstrating a significantly higher specificity than working memory (β = 0.98, z = 2.11, P = 0.04). Studies involving older, chronic patients with SCZ reported higher sensitivity (P <0.015) and specificity (P <0.001) than those involving younger, first‐episode patients or high‐risk individuals for psychosis. Additionally, we found that the severity of negative symptoms was positively associated with the specificity of the classification model (β = 7.19, z = 2.20, P = 0.03). Taken together, these results support the potential of using task‐based fMRI data in combination with machine learning techniques to identify biomarkers related to symptom outcomes in SCZ, providing a promising avenue for improving diagnostic accuracy and treatment efficacy. Future attempts to deploy ML classification should consider the factors of algorithm choice, data quality and quantity, as well as issues related to generalization.
Committed to staying single: Adapting the investment model of commitment processes to study singlehood
Authors: Beauparlant Emily T. , Machia Laura V. , Oh Jeewon
Published: November 2023

In the current work, we adapt the investment model of commitment processes for single adults. Across two cross‐sectional studies using undergraduate and internet samples (total N = 647), we tested whether the same factors that predict relationship commitment (investment, satisfaction, and quality of alternatives) also predict commitment to singlehood. In line with this theoretical model, we found that singlehood satisfaction and investment in singlehood were each positively associated with commitment to singlehood, whereas the quality of alternatives to singlehood was negatively associated with commitment to singlehood. We also found that a person's expected satisfaction and planned investment were each associated with commitment to singlehood, whereas subjective norms were not associated with commitment to singlehood. In addition, we tested whether commitment to singlehood was positively associated with well‐being, but these associations were nonsignificant. Our findings provide initial evidence for the appropriateness of the investment model for understanding commitment to being single.
Medication adherence in pediatric kidney transplantation: How to build a bridge over troubled water
Authors: Dobbels Fabienne , Wray Jo
Published: November 2023

Adhering to the immunosuppressive regimen remains one of the biggest challenges for children and adolescents after kidney transplantation. The first paper on nonadherence, co‐authored by Dr. Fine, appeared in Pubmed over 45 years ago. Since then, many clinicians and researchers tried to better understand nonadherence and are looking for effective ways to support young people in implementing the complex medication regimen in their daily lives. As a tribute to Dr. Fine, we conducted a comprehensive review providing an overview of adherence‐enhancing interventions in the field of pediatric kidney transplantation, thereby focusing on strategies that not only are effective but can also be embedded in daily clinical practice successfully and sustainably. This overview is preceded by a discussion about how to find out who is in need of supportive interventions. We will also argue that interventions should already start before pediatric kidney transplantation and discuss how to decide whether or not a young patient with nonadherence‐induced graft loss should undergo retransplantation. We hope this comprehensive overview will rekindle the hope that we can finally turn the tide and beat one of pediatric kidney transplantation's main enemies.
Identifying a core protein signature of small extracellular vesicles derived from B‐cell precursor acute lymphoblastic leukaemia
Authors: Saidu Nathaniel Edward Bennett , Aarsund Miriam , Sørensen Eva , Stensland Maria , Nyman Tuula Anneli , Ulvmoen Aina , Wu Yunjie , Inngjerdingen Marit
Published: November 2023

Acute paediatric leukaemia is diagnosed and monitored via bone marrow aspirate assessment of blasts as a measure of minimal residual disease. Liquid biopsies in the form of blood samples could greatly reduce the need for invasive bone marrow aspirations, but there are currently no blood markers that match the sensitivity of bone marrow diagnostics. Circulating extracellular vesicles (EVs) represent candidate biomarkers that may reflect the blast burden in bone marrow, and several studies have reported on the utility of EVs as biomarkers for adult haematological malignancies. Increased levels of EVs have been reported for several haematological malignancies, and we similarly report here elevated EV concentrations in plasma from paediatric BCP‐ALL patients. Plasma EVs are very heterogeneous in terms of their cellular origin, thus identifying a cancer selective EV‐marker is challenging. Here, we undertook a reductionistic approach to identify protein markers selectively associated to plasma EVs derived from BCP‐ALL patients. The EV proteome of primary BCP‐ALL cell‐derived EVs were compared against EVs from healthy donor B cells and the BCP‐ALL cell line REH, and further against EVs isolated from plasma of healthy paediatric donors and paediatric BCP‐ALL patients. With this approach, we identified a signature of 6 proteins (CD317, CD38, IGF2BP1, PCNA, CSDE1, and GPR116) that were specifically identified in BCP‐ALL derived EVs only and not in healthy control EVs, and that could be exploited as diagnostic biomarkers.
Fluidity in capability: Longitudinal assessments of suicide capability using ecological momentary assessments
Authors: Bayliss Luke T. , Hughes Christopher D. , Lamont‐Mills Andrea , du Plessis Carol
Published: November 2023

Introduction

Suicide capability is posited to facilitate the movement from ideation‐to‐action. Emerging evidence suggests capability comprises both trait‐ and state‐like facets. This study examined fluctuations in and associations of acquired, dispositional, practical, and perceived capabilities, and suicidal mental imagery, and suicidal ideation.

Method

Seventy‐five adults (48 females, Mage = 36.53 years) with lived experience of suicidal ideation and/or attempt responded to four prompts per day for 2 weeks that assessed suicide capability and suicidal ideation. Mean‐squared successive differences and probability of acute change indices and multilevel models were used for analyses.

Results

All facets of suicide capability fluctuated. Acquired and dispositional capabilities were trait‐like, with practical and perceived capabilities being state‐like. Suicidal mental imagery was the only facet of suicide capability that distinguished participants with a suicide attempt in the past 12 months from participants with a suicide attempt more than 1 year ago and suicide ideators. Suicidal mental imagery was associated with concurrent suicidal ideation and predictive of next assessment suicidal ideation.

Conclusion

Suicidal mental imagery may be uniquely associated with suicide capability. This study suggests there are trait‐ and state‐like facets of capability that can combine to potentially ready an individual to engage in suicidal behaviors.
Social integration in the activity peer group in sport and non‐sport organized activities: Links with depressive symptoms in adolescence
Authors: White‐Gosselin Charles‐Étienne , Poulin François , Denault Anne‐Sophie
Published: November 2023

Organized activities can provide a conducive context for various social processes that may prevent internalizing problems. Some types of organized activities, such as team sports, seem particularly favorable to these positive experiences. The aim of this 4‐year longitudinal study is to describe the changes in the feeling of social integration into the organized activity peer group and to examine whether this social process predicts depressive symptoms in adolescence. Team sports also are proposed to promote a high sense of social integration. A total of 292 adolescents (62% female) were followed annually from ages 14 to 17. The type of main organized activity practiced and the feeling of social integration into the activity peer group was measured each year. Depressive symptoms were self‐reported at the beginning and end of this period. Latent growth analyses showed that social integration into the organized activity peer group was high and decreasing during adolescence. Social integration was higher in team sports compared to individual sports and non‐sport activities as a whole. Finally, a high and sustained level of social integration during adolescence was associated with a low level of depressive symptoms at the end of adolescence, controlling for important covariates. These results suggest that organized activities, particularly team sports, provide a favorable context for developing a feeling of social integration, and that this may protect against depressive symptoms.
The novel allele, HLA‐B*15:627 was identified by next‐generation sequencing in a Chinese cord blood donor
Authors: Tao Sudan , You Xuan , Wang Fang , Zhang Wei , Zhu Faming
Published: November 2023

HLA‐B*15:627 shows one nucleotide substitution G to A at position 601 compared with HLA‐B*15:02:01:01.
Does Technological Intensity Matter for Global Cross‐Border Mergers and Acquisitions in Manufacturing, 1998–2018?
Authors: Huang Xiaodong , Yeung Godfrey , Du Debin
Published: November 2023

Despite being a key feature of the globalising world since the 1980s, the patterns and relationships between acquirer and target firms in cross‐border mergers and acquisitions (M&As) have only gained attention in recent years. By examining the data between 1998 and 2018 through multinomial logistic regression models, this paper investigates the goodness of match on technological intensity (the closeness of technological capabilities) between acquirer and target firms and the effects of geographical, cultural and institutional proximity in global cross‐border M&As in manufacturing sectors. Our results suggest that firms are more likely to acquire overseas counterparts with similar levels of technological intensity in manufacturing. Moreover, geographical proximity is significant in the M&As of target firms in low‐tech and medium‐low‐tech sectors, while cultural and institutional proximity matter for cross‐border M&As among medium‐high‐tech and high‐tech firms. High‐tech acquirer firms in advanced economies tend to acquire their high‐tech counterparts located in larger economies, while technological intensity is more important for high‐tech acquirer firms based in non‐advanced economies, as the closeness of technological knowledge with potential target firms allows them to generate potential synergies and overcome cultural gaps and foreignness in distant host countries.
Risk factors for positive follow‐up blood cultures in Gram‐negative bacteremia among immunocompromised patients with neutropenia
Authors: Ranganath Nischal , Yetmar Zachary A. , Saleh Omar Abu , Tande Aaron J. , Shah Aditya S.
Published: November 2023

Introduction

Gram‐negative bacillary bloodstream infection (GN‐BSI) is a frequent clinical challenge among immunocompromised hosts and is associated with a high mortality. The utility of follow‐up blood cultures (FUBCs) for GN‐BSI in this population, particularly in the setting of neutropenia, is poorly defined.

Methods

We conducted a single‐center, retrospective cohort study between the period of July 2018 and April 2022 to investigate the utility of FUBCs and delineate risk factors for positive cultures among neutropenic patients with monomicrobial GN‐BSI. Univariate logistic regression was performed to assess risk factors associated with positive FUBCs.

Results

Of 206 patients, 98% had FUBCs performed, and 9% were positive. Risk factors for positive FUBCs included multidrug‐resistant GN infection (OR 3.26; 95% confidence interval [CI] 1.22–8.72) and vascular catheter source (OR 4.82; CI 1.76–13.17). Among patients lacking these risk factors, the prevalence of positive FUBCs was low (2.8%) and the negative predictive value was 92%. Those with positive and negative FUBCs had similar rates of all‐cause mortality (16.7% vs. 16.6%; p = .942) and microbiologic relapse (11.1% vs. 6.0%; p = .401) within 90‐days of treatment completion. However, positive FUBCs were associated with prolonged hospitalization and longer duration of antimicrobial therapy.

Conclusion

Positive FUBCs were infrequent in neutropenic patients with GN‐BSI, and their occurrence did not significantly impact mortality or microbiologic relapse. Risk factors for positive FUBCs included multidrug resistant Gram‐negative infection and vascular catheter source. Prospective studies will be necessary to elucidate the benefits and risks of FUBCs when managing GN‐BSI in patients with underlying immune compromise.

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Anti‐dumping policy in Japan: From passive to active and self‐disciplined anti‐dumping actions
Authors: Shibayama Chisato
Published: November 2023

While Japan's anti‐dumping (AD) legislation has a long history, the use of AD policies in Japan was limited until the 2010s. This study analyses the evolution of Japan's AD policy over more than 100 years and its background across four periods: (1) from the AD Law's enactment in 1920 to the establishment of the General Agreement on Tariffs and Trade (GATT); (2) from the establishment of GATT to 1990, when no investigation or taxation was conducted; (3) from 1991 to 2008, a period of trial‐and‐error in AD procedures; and (4) the period after 2009 when the legal system and procedures were improved, and AD measures were being used more. In addition, we discuss the characteristics of industries that applied for AD. The reasons for the low number of AD measures in Japan vary by period and are driven by the circumstances of the prevailing times.
B‐cell leukemia in an adult sheep
Authors: Furtado Adriana P. , Fry Lindsay M. , Piel Lindsay M. W. , Bastos Reginaldo G. , Schneider David A. , Varvil Mara S.
Published: November 2023

B‐cell leukemia is a rare form of hematologic neoplasia in sheep, especially in adult animals. We present a case report of a 5‐year‐old WhiteFace Sheep wether with suspected acute lymphoblastic leukemia. The patient, a second‐generation relative of ewes experimentally inoculated with atypical scrapie, exhibited acute lethargy and loss of appetite. Laboratory investigation revealed marked leukocytosis, lymphocytosis, and abnormal serum chemistry panel results. Microscopic examination of blood and bone marrow smears exhibited a high percentage of large neoplastic cells with lymphoid characteristics. Histopathologic analysis of the spleen, liver, lungs, and other organs confirmed the presence of widespread tissue infiltration by neoplastic cells. Immunohistochemical labeling demonstrated strong intracytoplasmic labeling for CD20, consistent with B‐cell neoplasia. Flow cytometric analysis confirmed the B‐cell lineage of the neoplastic cells. Screening for bovine leukemia virus, which can experimentally cause leukemia in sheep, yielded a negative result. In this case, the diagnosis of B‐cell leukemia was supported by a comprehensive panel of diagnostic evaluations, including cytology, histopathology, immunohistochemistry, and immunophenotyping. This case report highlights the significance of accurate diagnosis and classification of hematologic neoplasia in sheep, emphasizing the need for immunophenotyping to aid in the diagnosis of B‐cell leukemia. It also emphasizes the importance of considering spontaneous leukemia as a differential diagnosis in sheep with lymphoid neoplasia, especially in the absence of circulating infectious diseases.
Efficacy of morning versus afternoon aerobic exercise training on reducing metabolic syndrome components: A randomized controlled trial
Authors: Morales‐Palomo Felix , Moreno‐Cabañas Alfonso , Alvarez‐Jimenez Laura , Mora‐Gonzalez Diego , Ortega Juan F. , Mora‐Rodriguez Ricardo
Published: November 2023

A supervised intense aerobic exercise program improves the health of individuals with metabolic syndrome (MetS). However, it is unclear whether the timing of training within the 24 h day would influence those health benefits. The present study aimed to determine the influence of morning vs. afternoon exercise on body composition, cardiometabolic health and components of MetS. One hundred thirty‐nine individuals with MetS were block randomized into morning (AMEX; n = 42) or afternoon (PMEX; n = 59) exercise training groups, or a non‐training control group (Control; n = 38). Exercise training was comprised of 48 supervised high‐intensity interval sessions distributed over 16 weeks. Body composition, cardiorespiratory fitness (assessed by ), maximal fat oxidation (FOmax), blood pressure and blood metabolites were assessed before and after the intervention. Compared with the non‐training Control, both exercise groups improved similarly body composition (–0.7% fat loss; P = 0.002), waist circumference (–2.1 cm; P < 0.001), diastolic blood pressure (–3.8 mmHg; P = 0.004) and (3.5 mL kg−1  min−1; P < 0.001) with no differences between training groups. AMEX, in comparison with PMEX, reduced systolic blood pressure (–4% vs. –1%; P = 0.019), plasma fasting insulin concentration (–12% vs. –5%; P = 0.001) and insulin resistance (–14% vs. –4%; P = 0.006). Furthermore, MetS Z score was further reduced in the AMEX compared to PMEX (–52% vs. –19%; P = 0.021) after training. In summary, high‐intensity aerobic exercise training in the morning in comparison to training in the afternoon is somewhat more efficient at reducing cardiometabolic risk factors (i.e. systolic blood pressure and insulin sensitivity).

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Key points

The effect of exercise time of day on health promotion is an area that has gained interest in recent years; however, large‐scale, randomized‐control studies are scarce.

People with metabolic syndrome (MetS) are at risk of developing cardiometabolic diseases and reductions in this risk with exercise training can be precisely gauged using a compound score sensitive to subtle evolution in each MetS component (i.e. Z score).

Supervised aerobic exercise for 16 weeks (morning and afternoon), without dietary restriction, improved cardiorespiratory and metabolic fitness, body composition and mean arterial pressure compared to a non‐exercise control group.

However, training in the morning, without changes in exercise dose or intensity, reduced systolic blood pressure and insulin resistance further compared to when training in the afternoon.

Thus, high‐intensity aerobic exercise training in the morning is somewhat more efficient in improving the health of individuals with metabolic syndrome.