bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Figure 4 from Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages
Authors: Manara Maria Cristina , Manferdini Cristina , Cristalli Camilla , Carrabotta Marianna , Santi Spartaco , De Feo Alessandra , Caldoni Giulia , Pasello Michela , Landuzzi Lorena , Lollini Pier-Luigi , Salamanna Francesca , Dominici Sabrina , Fiori Valentina , Magnani Mauro , Lisignoli Gina , Scotlandi Katia
Published: February 2024

Supplementary Figure 4
Supplementary Figure 10 from Engagement of CD99 Activates Distinct Programs in Ewing Sarcoma and Macrophages
Authors: Manara Maria Cristina , Manferdini Cristina , Cristalli Camilla , Carrabotta Marianna , Santi Spartaco , De Feo Alessandra , Caldoni Giulia , Pasello Michela , Landuzzi Lorena , Lollini Pier-Luigi , Salamanna Francesca , Dominici Sabrina , Fiori Valentina , Magnani Mauro , Lisignoli Gina , Scotlandi Katia
Published: February 2024

Supplementary Figure 10
Data from M9657 Is a Bispecific Tumor-Targeted Anti-CD137 Agonist That Induces MSLN-Dependent Antitumor Immunity without Liver Inflammation
Authors: Xu Chunxiao , Zhou Xueyuan , Webb Lindsay , Yalavarthi Sireesha , Zheng Wenxin , Saha Somdutta , Schweickhardt Rene , Soloviev Maria , Jenkins Molly H. , Brandstetter Susanne , Belousova Natalya , Alimzhanov Marat , Rabinovich Brian , Deshpande Amit M. , Brewis Neil , Helming Laura
Published: February 2024

Abstract
The costimulatory receptor CD137 (also known as TNFRSF9 or 4-1BB) sustains effective cytotoxic T-cell responses. Agonistic anti-CD137 cancer immunotherapies are being investigated in clinical trials. Development of the first-generation CD137-agonist monotherapies utomilumab and urelumab was unsuccessful due to low antitumor efficacy mediated by the epitope recognized on CD137 or hepatotoxicity mediated by Fcγ receptors (FcγR) ligand–dependent CD137 activation, respectively. M9657 was engineered as a tetravalent bispecific antibody (mAb2) in a human IgG1 backbone with LALA mutations to reduce binding to FCγRs. Here, we report that M9657 selectively binds to mesothelin (MSLN) and CD137 with similar affinity in humans and cynomolgus monkeys. In a cellular functional assay, M9657 enhanced CD8+ T cell–mediated cytotoxicity and cytokine release in the presence of tumor cells, which was dependent on both MSLN expression and T-cell receptor/CD3 activation. Both FS122m, a murine surrogate with the same protein structure as M9657, and chimeric M9657, a modified M9657 antibody with the Fab portion replaced with an anti-murine MSLN motif, demonstrated in vivo antitumor efficacy against various tumors in wild-type and human CD137 knock-in mice, and this was accompanied by activated CD8+ T-cell infiltration in the tumor microenvironment. The antitumor immunity of M9657 and FS122m depended on MSLN expression density and the mAb2 structure. Compared with 3H3, a murine surrogate of urelumab, FS122m and chimeric M9657 displayed significantly lower on-target/off-tumor toxicity. Taken together, M9657 exhibits a promising profile for development as a tumor-targeting immune agonist with potent anticancer activity without systemic immune activation and associated hepatotoxicity.
Supplementary Figure S6 from Aberrant Upregulation of RUNX3 Activates Developmental Genes to Drive Metastasis in Gastric Cancer
Authors: Suda Kazuto , Okabe Atsushi , Matsuo Junichi , Chuang Linda Shyue Huey , Li Ying , Jangphattananont Nawaphat , Mon Naing Naing , Myint Khine Nyein , Yamamura Akihiro , So Jimmy Bok-Yan , Voon Dominic Chih-Cheng , Yang Henry , Yeoh Khay Guan , Kaneda Atsushi , Ito Yoshiaki
Published: February 2024

Higher WNT5A expression in gastric cancer patients is associated with advanced stage TCGA gastric cancer patient dataset was visualized by XENA software (UCSC, n=591). The RNA expression level of WNT5A between stage I (n=25) and stage IV (n=41) are shown; **, P < 0.01 by a two-tailed Student t test.
Supplementary Figure S1 from Aberrant Upregulation of RUNX3 Activates Developmental Genes to Drive Metastasis in Gastric Cancer
Authors: Suda Kazuto , Okabe Atsushi , Matsuo Junichi , Chuang Linda Shyue Huey , Li Ying , Jangphattananont Nawaphat , Mon Naing Naing , Myint Khine Nyein , Yamamura Akihiro , So Jimmy Bok-Yan , Voon Dominic Chih-Cheng , Yang Henry , Yeoh Khay Guan , Kaneda Atsushi , Ito Yoshiaki
Published: February 2024

Higher RUNX3 expression in gastric cancer patients is associated with advanced stage and disease progression A, B, TCGA gastric cancer patient dataset visualized by XENA software (UCSC, n=591). Comparison of the mRNA expression of RUNX3 between normal tissues (n=38) and primary tumors (n=411) (A) as well as between stage Ia (n=17) and stage IV (n=49) (B) are shown; **, P < 0.01 and *, P < 0.05 by a two-tailed Student t test. C, TCGA gastric cancer patient dataset from microarray (cBioPortal) was obtained to determine RUNX3 mRNA expression in patients with disease-free (n=22) or with recurrence and disease progression (n=5); *, P < 0.05 by a two-tailed Student t test. D, comparison of survival data in RUNX3 high (red, n=349) or low (black, n=526) patients samples using microarrays obtained from KM-plotter database; P < 0.001.
FIGURE 2 from Aberrant Upregulation of RUNX3 Activates Developmental Genes to Drive Metastasis in Gastric Cancer
Authors: Suda Kazuto , Okabe Atsushi , Matsuo Junichi , Chuang Linda Shyue Huey , Li Ying , Jangphattananont Nawaphat , Mon Naing Naing , Myint Khine Nyein , Yamamura Akihiro , So Jimmy Bok-Yan , Voon Dominic Chih-Cheng , Yang Henry , Yeoh Khay Guan , Kaneda Atsushi , Ito Yoshiaki
Published: February 2024

RUNX3 drives metastasis in gastric cancer cells. A, Subcutaneous xenograft tumors were obtained by inoculation of 1 × 106 HGC-27 control and RUNX3 KO cells, respectively. Typical images are shown (n = 5). B, The weight of tumors was quantified; ****, P < 0.0001 by a two-tailed Student t test. C, Liver metastasis model by splenic inoculation of 1 × 106 HGC-27 cells. Representative images of tumors in liver metastasis in control, RUNX3 KO, and RUNX3 KO rescued with reintroduction of RUNX3 (RUNX3 OE) cells are shown (n = 5, respectively). D, Percentage of the metastatic tumor area in the liver tissue was measured using Image J and graphed (mean + SD); **, P < 0.01; *, P < 0.05 by a two-tailed Student t test. E, Representative images of tumor formation in spleen by inoculation of 1 × 106 HGC-27 cells in control and RUNX3 KO are shown (n = 5, respectively). F, The weight of tumors in spleen was quantified. G, Kaplan–Meier plots in liver metastasis models present overall survival for mice after inoculation of control and RUNX3 KO of HGC-27 cells; *, P < 0.05 by a two-tailed Student t test. H, Orthotopic transplantation model of 1 × 106 HGC-27 cells. Representative images of tumors in stomach (1 in blue, circled by dot line), peritoneal invasion (2, circled by dot line), and liver metastasis (3, indicated by an arrow head) in control, and also tumors in stomach (circled by dot line) in RUNX3 KO cells are shown (n = 5).
From Rare Disorders of Kidney Tubules to Acute Renal Injury: Progress and Prospective
Authors: Li Jiaying , Hou Fangxing , Lv Ning , Zhao Ruohuan , Zhang Lei , Yue Cai , Nie Min , Chen Limeng
Published: February 2024

Background: Acute kidney injury (AKI) is a severe condition marked by rapid renal function deterioration and elevated mortality, with traditional biomarkers lacking sensitivity and specificity. Rare tubulointerstitial diseases encompass a spectrum of disorders, primarily including monogenic diseases, immune-related conditions, and drug-induced tubulointerstitial diseases. The clinical manifestations vary from electrolyte and acid-base imbalances to kidney function insufficiency, which is associated with AKI in up to 20% of cases. Evidence indicated that rare tubulointerstitial diseases might provide new conceptual insights and perspectives for novel biomarkers and potential therapeutic strategies for AKI. Summary: Autosomal dominant tubulointerstitial kidney disease (ADTKD) and Fanconi syndrome (FS) are rare tubulointerstitial diseases. In ADTKD, UMOD and REN are closely related to AKI by affecting oxidative stress and tubuloglomerular feedback, which provide potential new biomarkers for AKI. Both rare tubulointerstitial diseases and AKI share etiologies and treatment responses. From the mechanism standpoint, rare tubulointerstitial diseases and AKI involve tubular transporter injury, initially manifesting as tubular dysfunction in tubulointerstitial disorder and progressing to AKI because of the programmed cell death with apoptosis, pyroptosis, or necroptosis of proximal tubule cells. Additionally, mitochondrial dysfunction has been identified as a common mechanism in both tubulointerstitial diseases and AKI induced by drugs, pSS, or monoclonal diseases. In the end, both AKI and FS patients and animal models responded well to the therapy of the primary diseases. Key Messages: In this review, we describe an overview of ADTKD and FS to identify their associations with AKI. Mitochondrial dysfunction contributes to rare tubulointerstitial diseases and AKI, which might provide a potential therapeutic target.
A Comprehensive Study on the Association between Plasma NOV/CCN3 Levels and Insulin Resistance in Childhood Obesity
Authors: Liu Yuesheng , Hao Lijun , Yin Chunyan , Li Min , Xiao Yanfeng
Published: February 2024

Introduction: Childhood obesity is a global health problem that is associated with various metabolic complications, such as insulin resistance, type 2 diabetes, dyslipidemia, and cardiovascular diseases. The mechanisms underlying the development of insulin resistance in childhood obesity are not fully understood. Nephroblastoma overexpressed gene (NOV), also known as CCN3, is a member of the CCN family of matricellular proteins that modulate cell proliferation, differentiation, adhesion, migration, and survival. Previous studies have shown that NOV/CCN3 is involved in glucose metabolism and insulin signaling in various tissues and cell types. However, the role of NOV/CCN3 in childhood obesity and insulin resistance remains unclear. Methods: In this study, we aimed to investigate the association between plasma NOV/CCN3 levels and insulin resistance in 58 obese and 43 non-obese children aged 6–12 years. We measured plasma NOV/CCN3 levels by enzyme-linked immunosorbent assay and assessed insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR). We also collected clinical and biochemical data, such as body mass index (BMI), waist circumference (WC), blood pressure (BP), fasting glucose (FG), fasting insulin (FI), lipid profile, and inflammatory markers. Results: We found that plasma NOV/CCN3 levels were significantly higher in obese children than in non-obese children (p < 0.001) and positively correlated with BMI (r = 0.42, p < 0.001), WC (r = 0.38, p < 0.001), BP (r = 0.35, p < 0.001), FG (r = 0.31, p < 0.001), FI (r = 0.45, p < 0.001), HOMA-IR (r = 0.48, p < 0.001), triglycerides (r = 0.28, p < 0.001), low-density lipoprotein cholesterol (r = 0.26, p < 0.001), and C-reactive protein (CRP) (r = 0.32, p < 0.001). Multiple linear regression analysis revealed that plasma NOV/CCN3 levels were independently associated with HOMA-IR after adjusting for age, sex, BMI, WC, BP, FG, FI, lipid profile, and CRP (β = 0.36, p < 0.001). Conclusion: These results suggest that plasma NOV/CCN3 levels are elevated in childhood obesity and are associated with insulin resistance, indicating that NOV/CCN3 may play a role in the pathogenesis of metabolic disorders in obese children.
Sunitinib for Metastatic Renal Cell Carcinoma: Real-World Data from the STAR-TOR Registry and Detailed Literature Review
Authors: Uhlig Annemarie , Bergmann Lothar , Bögemann Martin , Fischer Thomas , Goebell Peter J. , Leitsmann Marianne , Reichert Mathias , Rink Michael , Schlack Katrin , Trojan Lutz , Uhlig Johannes , Woike Michael , Strauß Arne
Published: February 2024

Introduction: We evaluated the effectiveness and safety profile of the tyrosine kinase inhibitor sunitinib in patients with advanced or metastatic renal cell carcinoma (a/mRCC) in a real-world setting. Methods: We analyzed data of adult a/mRCC patients treated with sunitinib. Data were derived from the German non-interventional post-approval multicenter STAR-TOR registry (NCT00700258). Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated using descriptive statistics and survival analyses for the entire cohort and patient subgroups. Results: A total of 116 study sites recruited 702 patients treated with sunitinib (73.1% male; median age 68.0 years; median Karnofsky index 90%) between November 2010 and May 2020. The most frequent histological subtype was clear cell RCC (81.6%). Sunitinib was administered as first-line treatment in 83.5%, as second line in 11.7%, and as third line or beyond in 4.8% of the patients. Drug-related AEs and serious AEs were reported in 66.3% and 13.9% of the patients, respectively (most common AE: gastrointestinal disorders; 39.7% of all patients). Conclusions: This study adds further real-world evidence of the persisting relevance of sunitinib for patients with a/mRCC who cannot receive or tolerate immune checkpoint inhibitors. The study population includes a high proportion of patients with unfavorable MSKCC poor-risk score, but shows still good PFS and OS results, while the drug demonstrates a favorable safety profile. The STAR-TOR registry is also registered in the database of US library of medicine (NCT00700258).
Demystifying Skeletal Dysplasias: A Practical Approach for the Pediatric Endocrinologist
Authors: Colares Neto Guido de Paula , Alves Crésio de Aragão Dantas
Published: February 2024

Background: Skeletal dysplasias encompass a group of genetic conditions associated with cartilaginous and bone tissue abnormalities, exhibiting a variable phenotype depending on the involved genes and mechanisms. Differential diagnosis is challenging as there are many skeletal dysplasias with similar phenotypes. Summary: In this review, we describe the physiology of skeletal development and the classification of skeletal dysplasias, followed by a practical approach to the workup of a child with suspected skeletal dysplasia. Diagnosis requires clinical, laboratory, and radiological evaluation to differentiate potential conditions in the patient. Genotyping has emerged as a confirmatory tool in many cases, enabling personalized treatment through a multidisciplinary approach and assessment of associated comorbidities. Key Messages: As skeletal dysplasias often present with short stature, proportionate or disproportionate, the pediatric endocrinologist plays a crucial role in initial investigative and diagnostic guidance. Identifying the critical clinical manifestations, conducting appropriate initial screening tests, and referring for multidisciplinary follow-up contribute to expeditious diagnosis and family support.
The Right to Language in School: Russian Sámi
Authors: Zmyvalova Ekaterina
Published: February 2024

This paper is about Sámi children’s right to learn their language in school in Russia (henceforth referred to as RtL). First, the core elements of this right are deduced from the international and regional instruments. These elements are legal recognition, non-discrimination, participation, appropriate education, and high-quality education. Then, the Russian legal acts are analysed to identify to what extent these elements are present in the Russian legal acts. The paper demonstrates that the five deduced elements of the RtL are found in the relevant Russian legal acts. However, the contents of some of these elements in the Russian legal acts are different from the contents of the corresponding elements deduced from the international and regional legal instruments. The paper also identifies challenges in the Russian legal acts that hinder the realisation of the RtL.
Hard-Target Reflection Laser Spectroscopy of Carbon Monoxide Gas Concentration for the Early Detection of Spontaneous Combustion of Coal
Authors: Somekawa Toshihiro , Manago Naohiro , Kurahashi Shinri , Shiina Tatsuo , Yogo Akifumi , Kuze Hiroaki
Published: February 2024

We report on the hard-target reflection spectroscopy of carbon monoxide (CO) gas based on the technique of infrared tunable diode laser absorption spectroscopy aiming at developing a low-cost yet sensitive sensor for the early detection of spontaneous coal combustion. A narrow-band distributed feedback laser emitting around 2333.7 nm is used to monitor CO gas molecules contained in a 5 cm gas cell. The light diffusely backscattered from the surface of a lump of coal placed at the end of a 50 cm light path is detected with a photodiode in the coaxial transmitter/receiver setup. From the variation of the detected signal profile with the CO partial pressure in the cell, the detection limit of the current system is estimated to be about 30 parts per million per meter (ppm·m), which meets the sensitivity required for monitoring the self-heating of coal in mines, silos, or stockpiles.
Nonsuicidal self-injury and intersubjective recognition: ‘You can’t argue with wounds’
Authors: Steggals Peter , Graham Ruth , Lawler Steph
Published: February 2024

This article explores the relevance of intersubjective recognition and the ‘recognition theoretical turn’ to our understanding of nonsuicidal self-injury. While previous research has demonstrated that self-injury possesses an important social dimension alongside its intrapsychic characteristics, a major challenge for any social approach to self-injury has been to find a way to describe and analyse this dimension without reductively implying that self-injury is a form of ‘attention-seeking’, where this describes a pejorative accusation of social manipulation. One possible solution to this challenge lies in the concept of intersubjective recognition and the idea that what some have interpreted as ‘attention-seeking’ behaviour is perhaps better understood as recognition-seeking. As such, we draw on data from a 2016–2017 English pilot study to examine three basic questions: (1) does self-injury constitute, at least in some cases and amongst its many other observed intrapsychic and social functions, a form of recognition-seeking? (2) if so, how does self-injury work as a claim to recognition? and (3), how do we solve the apparent contradiction of using a stigmatic mark as a means of claiming a normative status? Our study suggests that one of self-injury’s intersubjective imperatives is the need to be listened to and taken seriously, to have one’s feelings and experiences confirmed by others as being legitimate and valid. As such, intersubjective recognition does appear to form a distinct part of the overdetermined complex of meanings and effects associated with self-injury and may be an important factor in a number of cases.
A Whale of a Blindspot: The “Effectiveness” of Bribes, Threats, and Socialization in the International Whaling Commission
Authors: Lobo Rafaella
Published: February 2024

This paper contributes to broader efforts to de-center and historicize IR theory by bringing into question dominant narratives about developing country behavior at the International Whaling Commission (IWC). This literature either neglects, or actively erases any possibility of developing country agency; different blindspots work to the same effect, whereby developing country behavior is assumed rather than investigated, and behavioral change, such as a decision to join the IWC, vote a certain way, or abide by the whaling moratorium, is driven mostly by exogenous factors—threats, bribes, and persuasion. If a developing country choosing a pro-whaling stance is evidence of vote-buying, and an anti-whaling stance is evidence of coercion or socialization, then great power agency is assumed to exist and matter without being demonstrated—and the possibility of agency is denied to most of the world. I use the case of Brazil, the last country to give up whaling in the American continent, to de-center and historicize important whaling-related decisions made from the 1950s–1990s. Brazil voted against the commercial whaling moratorium in 1982 but has since given up whaling and become a leader in whale conservation. The empirical analysis not only finds scant support for the dominant explanations, but it also challenges them on several grounds—and thus underscores the need for theoretical lenses that allow for developing countries’ agencies to be acknowledged. More than contributing to inclusive scholarship, taking alternative perspectives seriously is imperative for more just conservation practice, and more legitimate global governance.
Social Control and Homeless Encampments: Shifting the Role of Shelters Through Judicial Review
Authors: Flynn Alexandra
Published: February 2024

In Canadian cities, unaffordable housing and the lack of community supports have led to an increase in the number of encampments in public spaces. Municipal governments argue that short-term shelter spaces are a reasonable response to the ongoing, amplified housing crisis. However, shelters are an example of the many ‘every day’ regulatory approaches used by public officials in related to unhoused people referenced by Johnsen et al., do not provide legal tenure, and are often unsafe for people and their possessions.
Primary Well-Differentiated Neuroendocrine Tumor/Carcinoid of the Prostate: Case Report and Review of Literature
Authors: Alhamar Mohamed , Sethi Shenon , Reuter Victor E. , Fine Samson W.
Published: February 2024

Primary well-differentiated neuroendocrine tumor (WDNT)/carcinoid of the genitourinary tract is rare. Many WDNT reported in the prostate gland have been seen in close association with conventional prostatic adenocarcinoma and/or label for prostate-specific immunohistochemical markers and are best considered prostatic adenocarcinomas with “carcinoid-like” features. We present a case of primary WDNT/carcinoid incidentally detected in a 67-year-old man who underwent radical prostatectomy for Grade group 2 prostatic adenocarcinoma. Morphologically, the neuroendocrine (NE) lesion appeared distinct from the prostatic adenocarcinoma, labeled for NE markers, was negative for prostatic markers (NKX3.1, PSA, and ERG), and showed an overall low Ki-67 proliferation index (<1%). Follow-up was uneventful with no evidence of residual disease or metastasis.
Starting a New Revolution in Nursing
Authors: Grant Ernest J.
Published: February 2024

The onset of COVID-19 and the murder of George Floyd shed light on social justice inequities, disparities in health care and the continuing rise of racism within society. Studies conducted by the American Nurses Foundation also revealed acts of racism within the nursing profession. The creation of the National Commission to Address Racism in Nursing and the American Nurses Association's issuance of an apology through its Racial Reckoning work have begun a revolution within the nursing profession to address this phenomenon. This commentary will provide a brief overview of collaborative initiatives currently underway and address ways in which nurses can do their part to obliterate racism from the nursing profession.
The conundrum of the habitual workplace: In search of access to justice for transport workers in the European Union
Authors: Carballo Piñeiro Laura
Published: February 2024

EU private international law regulations are articulated around the ‘habitual place of work’ factor, which does not fit well with the fact that not only are these workers mobile, but their place of work is also mobile. This article critically examines the proxy to this concept developed by the Court of Justice to provide transport workers with access to justice. There are some caveats to the chosen factual approach, in particular its complexity as well as the disregard for the collective dimension of employment relationships, since it can only be undertaken on a case-by-case basis. Moreover, this factual approach does not fit well to all transport sectors. The application of this approach considering the transport worker's domicile/habitual residence might enhance the said access to justice. A similar factual approach is employed in the Posting Drivers in the Road Transport Sector Directive which further compromises worker protection in this sector.
Advanced waveform analysis of the photoplethysmogram signal using complementary signal processing techniques for the extraction of biomarkers of cardiovascular function
Authors: Mathieu Aristide Jun Wen , Pascual Miquel Serna , Charlton Peter H , Volovaya Maria , Venton Jenny , Aston Philip J , Nandi Manasi , Alastruey Jordi
Published: February 2024

Introduction

Photoplethysmogram signals from wearable devices typically measure heart rate and blood oxygen saturation, but contain a wealth of additional information about the cardiovascular system. In this study, we compared two signal-processing techniques: fiducial point analysis and Symmetric Projection Attractor Reconstruction, on their ability to extract new cardiovascular information from a photoplethysmogram signal. The aim was to identify fiducial point analysis and Symmetric Projection Attractor Reconstruction indices that could classify photoplethysmogram signals, according to age, sex and physical activity.

Methods

Three datasets were used: an in-silico dataset of simulated photoplethysmogram waves for healthy male participants (25–75 years old); an in-vivo dataset containing 10-min photoplethysmogram recordings from 57 healthy subjects at rest (18–39 or > 70 years old; 53% female); and an in-vivo dataset containing photoplethysmogram recordings collected for 4 weeks from a single subject, in daily life. The best-performing indices from the in-silico study (5/48 fiducial point analysis and 6/49 Symmetric Projection Attractor Reconstruction) were applied to the in-vivo datasets.

Results

Key fiducial point analysis and Symmetric Projection Attractor Reconstruction indices, which showed the greatest differences between groups, were found to be consistent across datasets. These indices were related to systolic augmentation, diastolic peak positioning and prominence, and waveform variability. Both fiducial point analysis and Symmetric Projection Attractor Reconstruction techniques provided indices that supported the classification of age and physical activity, but not sex.

Conclusions

Both fiducial point analysis and Symmetric Projection Attractor Reconstruction techniques demonstrated utility in identifying cardiovascular differences between individuals and within an individual over time. Future research should investigate the potential utility of these techniques for extracting information on fitness and disease, to support healthcare-decision making.
Business Expansion Through Cor Theory: The Case of Cafe Lola
Authors: Ji Yuze ‘Crystal’ , Cain Lisa
Published: February 2024

Lin Jerome, J.D. and Alexandra Lourdes, Ph.D. have established an entrepreneurial empire in Las Vegas, Nevada. Their impressive portfolio includes The Refined Agency, Café Lola, Saint Honoré Doughnuts & Beignets, and Pizza Anonymous. According to the Conservation of Resources (COR) theory, businesses are more likely to put resources and effort into interactions that they consider worthwhile and that can generate more value in the future when considering business expansion. By examining how The Refined Agency, Café Lola, Saint Honoré Doughnuts & Beignets, and Pizza Anonymous relate to and support one another, this case study investigates the application of the Conservation of Resources (COR) theory from a business perspective. Thoughtful discussions on next steps for these entrepreneurs and their benchmark social media marketing efforts are discussed.
Tax Administration Reform: End of Tax Disputes in India?
Authors: Deb Rajat Deb
Published: February 2024

A long-due Indian direct tax administrative reform for removing the taxpayers’ plight and widening the tax base gained momentum by introducing the faceless assessments and appeals scheme coupled with taxpayers’ tax charter. Following a descriptive approach, the study assesses whether the reform would end the tax disputes. Albeit, ideally, any tax system should be simple, efficient, transparent, and free from conflicts. The Indian taxation saga indicates an infamous tug-of-war between the taxpayers and the revenue-seeking tax officers. Serving strange tax demand notices and retrospective amendments of the tax laws created a phobia of ‘tax terrorism’ in honest taxpayers’ minds. Considering this, the government followed the digital route with no physical interaction between the taxpayers and tax officers for tax assessments and appeals. Moreover, fixing the responsibilities of the taxpayers and tax officers would minimize tax disputes substantially if addressing the apprehensions and teething problems appropriately, addressing the apprehensions and teething problems.
Venous and arterial thrombosis in patients with VEXAS syndrome
Authors: Kusne Yael , Ghorbanzadeh Atefeh , Dulau-Florea Alina , Shalhoub Ruba , Alcedo Pedro E. , Nghiem Khanh , Ferrada Marcela A. , Hines Alexander , Quinn Kaitlin A. , Panicker Sumith R. , Ombrello Amanda K. , Reichard Kaaren , Darden Ivana , Goodspeed Wendy , Durrani Jibran , Wilson Lorena , Olteanu Horatiu , Lasho Terra , Kastner Daniel L. , Warrington Kenneth J. , Mangaonkar Abhishek , Go Ronald S. , Braylan Raul C. , Beck David B. , Patnaik Mrinal M. , Young Neal S. , Calvo Katherine R. , Casanegra Ana I. , Grayson Peter C. , Koster Matthew J. , Wu Colin O. , Kanthi Yogendra , Patel Bhavisha A. , Houghton Damon E. , Groarke Emma M.
Published: February 2024

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, caused by somatic mutations in UBA1, is an autoinflammatory disorder with diverse systemic manifestations. Thrombosis is a prominent clinical feature of VEXAS syndrome. The risk factors and frequency of thrombosis in VEXAS syndrome are not well described, due to the disease’s recent discovery and the paucity of large databases. We evaluated 119 patients with VEXAS syndrome for venous and arterial thrombosis and correlated their presence with clinical outcomes and survival. Thrombosis occurred in 49% of patients, mostly venous thromboembolism (VTE; 41%). Almost two-thirds of VTEs were unprovoked, 41% were recurrent, and 20% occurred despite anticoagulation. The cumulative incidence of VTE was 17% at 1 year from symptom onset and 40% by 5 years. Cardiac and pulmonary inflammatory manifestations were associated with time to VTE. M41L was positively associated specifically with pulmonary embolism by univariate (odds ratio [OR]: 4.58, confidence interval [CI] 1.28-16.21, P = .02) and multivariate (OR: 16.94, CI 1.99-144.3, P = .01) logistic regression. The cumulative incidence of arterial thrombosis was 6% at 1 year and 11% at 5 years. The overall survival of the entire patient cohort at median follow-up time of 4.8 years was 88%, and there was no difference in survival between patients with or without thrombosis (P = .8). Patients with VEXAS syndrome are at high risk of VTE; thromboprophylaxis should administered be in high-risk settings unless strongly contraindicated.
The 50% and 95% effective dose of remimazolam tosilate for anaesthesia induction in sleep disorders patients undergoing laparoscopic cholecystectomy: an up-and-down sequential allocation trial
Authors: Xiao Yue , Cao Yanan , Pu Jie , Guo Chendong , Yi Yanzi , Deng Youming , Hu Yimin
Published: February 2024

Purpose

Previous reports argue that preoperative sleep conditions of patients can influence the dosage of general anaesthesia drugs. Therefore, we aimed to investigate the dose-effect relationship of preoperative sleep disorders on the induction of general anaesthesia with remimazolam tosilate and calculate the Median effective (ED50) and 95% effective (ED95) dosages.

Methods

Included in our study were 56 patients who underwent laparoscopic cholecystectomy at our hospital. A separate group of 27 patients with sleep disorders (SD group) and 29 patients without sleep disorders (NSD group) using the Pittsburgh Sleep Quality Index (PSQI) were also included. According to the Dixon ‘up-and-down’ design, patients received remimazolam at preselected concentrations starting at 0.2 mg/kg. After the administration of remimazolam, loss of consciousness was observed. By observing whether consciousness disappeared within a minute, we adjusted the dose of remimazolam by 0.1 mg/kg (up and down) in the following patient. The Median effective dose (ED50), 95% effective dose (ED95), and 95% confidence interval (CI) of remimazolam for effective sedation were calculated.

Results

The ED50 of remimazolam was 0.226 mg/kg (95%CI 0.221–0.232 mg/kg) in the SD group and 0.191 mg/kg (95%CI, 0.183–0.199 mg/kg) in the NSD group. The ED95 of remimazolam was 0.237 mg/kg (95%CI 0.231–0.262 mg/kg) in the SD group and 0.209 mg/kg (95%CI 0.200–0.254 mg/kg) in the NSD group.

Conclusions

In the SD group, the ED50 and ED95 of remimazolam during anaesthesia induction were 0.226 and 0.237 mg/kg, respectively. The induction dose of remimazolam in the SD group was significantly higher than that in the NSD group.
High serum proteinase-3 levels predict poor progression-free survival and lower efficacy of bevacizumab in metastatic colorectal cancer
Authors: Furuya Kei , Nakajima Masao , Tsunedomi Ryouichi , Nakagami Yuki , Xu Ming , Matsui Hiroto , Tokumitsu Yukio , Shindo Yoshitaro , Watanabe Yusaku , Tomochika Shinobu , Maeda Noriko , Iida Michihisa , Suzuki Nobuaki , Takeda Shigeru , Hazama Shoichi , Ioka Tatsuya , Hoshii Yoshinobu , Ueno Tomio , Nagano Hiroaki
Published: February 2024

Background

To improve the prognosis of patients with metastatic colorectal cancer (mCRC), investigating predictive biomarkers of their prognosis and chemotherapeutic responsiveness is necessary. This study aimed to analyze the clinical significance of serum proteinase-3 (PRTN3) as a predictor for prognosis and chemosensitivity, especially to bevacizumab therapy, in mCRC.

Methods

This single-center retrospective observational study enrolled 79 patients with mCRC in our hospital and 353 patients with colorectal cancer in the TCGA database. Preoperative serum PRTN3 levels were measured using an enzyme-linked immunosorbent assay. The clinicopathological characteristics and prognosis according to serum PRTN3 levels were then evaluated. PRTN3 expression in tumor and stromal cells was evaluated immunohistochemically. The impact of PRTN3 levels on angiogenesis and bevacizumab sensitivity was evaluated using the tube formation assay.

Results

Serum PRTN3 levels were an independent poor prognostic factor for progression-free survival (PFS) (hazard ratio, 2.082; 95% confidence interval, 1.118-3.647; P=0.010) in patients with mCRC. Similarly, prognostic analysis with TCGA data sets showed poorer overall survival in patients with PRTN3 expression than that in patients without PRTN3 expression, especially in patients with stage IV. Immunohistochemical analysis of resected specimens revealed that stromal neutrophils expressed PRTN3, and their expression level was significantly correlated with serum PRTN3 levels. Interestingly, the effectiveness of first-line chemotherapy was significantly poorer in the high serum PRTN3 level group. High serum PRTN3 was significantly associated with poor PFS (hazard ratio, 3.027; 95% confidence interval, 1.175–7.793; P=0.0161) in patients treated with bevacizumab, an anti-angiogenic inhibitor. The tube formation assay revealed that PRTN3 administration notably augmented angiogenesis while simultaneously attenuating the anti-angiogenic influence exerted by bevacizumab therapy.

Conclusions

Serum PRTN3 levels could be a novel predictive biomarker of PFS of first-line chemotherapy, especially for bevacizumab therapy, in patients with mCRC
Cytokine profile in first-episode drug-naïve major depressive disorder patients with or without anxiety
Authors: Liang Jun , Xu Yayun , Gao Wenfan , Sun Yanhong , Zhang Yuanyuan , Shan Feng , Xia Qingrong
Published: February 2024

Objective

It is known that cytokines play a role in both depression and anxiety. This study aimed to compare the levels of multiple cytokines in patients with first-episode drug-naive major depressive disorder (MDD) with or without anxiety and analyze the correlation between the level of depression or anxiety and the serum cytokine levels.

Methods

The study involved 55 patients with first-episode drug-naive MDD. To assess anxiety symptoms, the 14-item HAMA was used. MDD patients were divided into two groups: 23 MDD patients without anxiety and 32 MDD patients with anxiety. The measurement of 37 cytokines was conducted. Serum cytokine levels between patients with MDD without anxiety and anxiety were compared. In multiple linear regression models, the relationship between the group and abnormal cytokines was explored. The receiver operating characteristic (ROC) curve analysis was performed to estimate diagnostic performance of serum cytokines in discriminating MDD patients with anxiety from MDD patients without anxiety. A correlation was evaluated between the scores of HAMD or HAMA and the serum cytokine levels.

Results

In MDD patients with anxiety, IL-17 C and CCL17 levels were significantly lower than in MDD patients without anxiety (all P < 0.05). Multiple measurements were corrected with Benjamini-Hochberger corrections, but none of these differences persisted (all P > 0.05). The results of multiple linear regression models revealed that after controlling for other independent variables, group was not a significant independent predictor of serum IL-17 C or CCL17 (all P > 0.05). The AUC values of IL-17 C and CCL17 were 0.643 and 0.637, respectively, in discriminating MDD patients with anxiety from MDD patients without anxiety. The results of partial correlation analyses showed the scores of HAMD were negatively correlated with the IL-17 C (r = -0.314, P = 0.021) levels with sex as a covariate.

Conclusions

The findings suggest that there is a potential absence of disparity in the levels of circulating cytokines among individuals diagnosed with first-episode drug-naïve MDD, regardless of the presence or absence of comorbid anxiety.
Process evaluation of school-based high-intensity interval training interventions for children and adolescents: a systematic review and meta-analysis of randomized controlled trials
Authors: Liu Yong , Wadey Curtis A. , Barker Alan R. , Williams Craig A.
Published: February 2024

Background

Several systematic reviews have been published to investigate the effectiveness of high-intensity interval training (HIIT) in schools. However, there has been limited attention given to understanding the functioning of the intervention processes, which is of paramount importance for interpreting and translating the intervention effectiveness. The aim of this systematic review is to determine the extent to which process evaluation is measured in school-based HIIT interventions and to explore the effects of process evaluation and intervention characteristics on cardiorespiratory fitness (CRF), body composition, muscular strength, and blood pressure.

Methods

A comprehensive search was conducted in SPORT Discus (EBSCOhost), Web of Science, Scopus, Medline (Ovid) and Cochrane Central Register of Controlled Trials. The extent to which process evaluation is measured was narratively reported, alongside with the guidance of process evaluation of complex interventions by UK Medical Research Council. Meta-analyses and meta-regressions were conducted to determine the effects of process evaluation and intervention characteristics to the intervention outcomes.

Results

The literature search identified 77 studies reporting on 45 school-based HIIT interventions. In total, five interventions reported process evaluation in a section or in a separate study, and only one intervention adopted a process evaluation framework. On average, 6 out of 12 process evaluation measures were reported in all interventions. Subgroup analyses did not indicate any beneficial treatment effects for studies with process evaluation group, whereas all pooled data and studies without process evaluation group showed significant improvement for CRF and body composition.

Conclusion

Process evaluation is frequently omitted in the literature of school-based HIIT in children and adolescents. Although reporting of process evaluation measures may not directly associate with better intervention outcomes, it allows accurate interpretation of intervention outcomes, thereby enhancing the generalisability and dissemination of the interventions.
Online public concern about allergic rhinitis and its association with COVID-19 and air quality in China: an informative epidemiological study using Baidu index
Authors: Yu Yi , Zhang Qinzhun , Yao Xinmeng , Wu Jinghua , He Jialu , He Yinan , Jiang Huaqiang , Lu Dongxin , Ye Chengyin
Published: February 2024

Background

Allergic rhinitis is a common health concern that affects quality of life. This study aims to examine the online search trends of allergic rhinitis in China before and after the COVID-19 epidemic and to explore the association between the daily air quality and online search volumes of allergic rhinitis in Beijing.

Methods

We extracted the online search data of allergic rhinitis-related keywords from the Baidu index database from January 23, 2017 to June 23, 2022. We analyzed and compared the temporal distribution of online search behaviors across different themes of allergic rhinitis before and after the COVID-19 pandemic in mainland China, using the Baidu search index (BSI). We also obtained the air quality index (AQI) data in Beijing and assessed its correlation with daily BSIs of allergic rhinitis.

Results

The online search for allergic rhinitis in China showed significant seasonal variations, with two peaks each year in spring from March to May and autumn from August and October. The BSI of total allergic rhinitis-related searches increased gradually from 2017 to 2019, reaching a peak in April 2019, and declined after the COVID-19 pandemic, especially in the first half of 2020. The BSI for all allergic rhinitis themes was significantly lower after the COVID-19 pandemic than before (all p values < 0.05). The results also revealed that, in Beijing, there was a significant negative association between daily BSI and AQI for each allergic rhinitis theme during the original variant strain epidemic period and a significant positive correlation during the Omicron variant period.

Conclusion

Both air quality and the interventions used for COVID-19 pandemic, including national and local quarantines and mask wearing behaviors, may have affected the incidence and public concern about allergic rhinitis in China. The online search trends can serve as a valuable tool for tracking real-time public concerns about allergic rhinitis. By complementing traditional disease monitoring systems of health departments, these search trends can also offer insights into the patterns of disease outbreaks. Additionally, they can provide references and suggestions regarding the public’s knowledge demands related to allergic rhinitis, which can further be instrumental in developing targeted strategies to enhance population-based disease education on allergic diseases.
Susceptibility of AutoML mortality prediction algorithms to model drift caused by the COVID pandemic
Authors: Kagerbauer Simone Maria , Ulm Bernhard , Podtschaske Armin Horst , Andonov Dimislav Ivanov , Blobner Manfred , Jungwirth Bettina , Graessner Martin
Published: February 2024

Background

Concept drift and covariate shift lead to a degradation of machine learning (ML) models. The objective of our study was to characterize sudden data drift as caused by the COVID pandemic. Furthermore, we investigated the suitability of certain methods in model training to prevent model degradation caused by data drift.

Methods

We trained different ML models with the H2O AutoML method on a dataset comprising 102,666 cases of surgical patients collected in the years 2014–2019 to predict postoperative mortality using preoperatively available data. Models applied were Generalized Linear Model with regularization, Default Random Forest, Gradient Boosting Machine, eXtreme Gradient Boosting, Deep Learning and Stacked Ensembles comprising all base models. Further, we modified the original models by applying three different methods when training on the original pre-pandemic dataset: (1) we weighted older data weaker, (2) used only the most recent data for model training and (3) performed a z-transformation of the numerical input parameters. Afterwards, we tested model performance on a pre-pandemic and an in-pandemic data set not used in the training process, and analysed common features.

Results

The models produced showed excellent areas under receiver-operating characteristic and acceptable precision-recall curves when tested on a dataset from January-March 2020, but significant degradation when tested on a dataset collected in the first wave of the COVID pandemic from April-May 2020. When comparing the probability distributions of the input parameters, significant differences between pre-pandemic and in-pandemic data were found. The endpoint of our models, in-hospital mortality after surgery, did not differ significantly between pre- and in-pandemic data and was about 1% in each case. However, the models varied considerably in the composition of their input parameters. None of our applied modifications prevented a loss of performance, although very different models emerged from it, using a large variety of parameters.

Conclusions

Our results show that none of our tested easy-to-implement measures in model training can prevent deterioration in the case of sudden external events. Therefore, we conclude that, in the presence of concept drift and covariate shift, close monitoring and critical review of model predictions are necessary.