bluuebunny/crossref_metadata_2025 huggingface dataset:
The Clinical Utility of Finding Unexpected Subclinical Spikes Detected by High-Density EEG During Neurodiagnostic Investigations
Authors: March Michael , Bar Omri , Chadehumbe Madeline , Catterall Kim , Mintz Mark
Published: September 2024

This study aimed to analyze the frequency of unexpected subclinical spikes (USCS) in pediatric patients who underwent high-density electroencephalogram (HD-EEG). Of the 4481 successful HD-EEG studies, 18.5% (829) were abnormal, and 49.7% of these abnormal studies showed SCS, of which 64.1% were USCS. USCS were found to be correlated with attention/concentration deficits and executive dysfunction, often accompanied by the dual psychiatric diagnosis of ADHD. MRI revealed abnormal findings in 32.6% of the subjects with USCS, such as abnormal signal or signal hyperintensity in brain parenchyma, temporal or arachnoid cysts, and vascular malformations. Moreover, the USCS group who received neuropsychiatric testing scored lower than the population mean on Full-Scale Intelligence Quotient, Working Memory Index, and Processing Speed Index. This study highlights the potential of USCS as biomarkers that can lead to changes in clinical management and outcomes, provide valuable information about pathophysiological mechanisms, and suggest potential treatment pathways.
Taking ‘nonsense’ seriously: Hoaxes, spoofs, and the epistemic cultures of geography
Authors: Hannah Matthew
Published: September 2024

The ‘Grievance Studies Affair’, a deceptive publishing project launched in 2017, offers a revealing lens through which to see beyond simplifying polarizations and establish more constructive relations among geography's wide range of ‘epistemic cultures’. This article places the Grievance Studies Affair in the context of other hoaxes and spoofs and draws upon speech act theory to pin down how such deceptive publications are supposed to work. The core of the argument concerns the epistemological interpretation of instances where writings purported by their authors to be ‘nonsense’ have nevertheless been seen by other scholars – even when it is clear that a hoax or spoof was intended – as sense-bearing, valuable, or potentially fruitful. These instances shed fresh light on two epistemological issues: the role of authorial intention in academic arguments, and how much we really need to know about other epistemic cultures to form serious judgments about them. Attending to these points can enhance the possibility of respectful and constructive conversations between epistemic cultures in geography.
The Relationship Between Perceived Social Support and Post-Traumatic Growth Among Medical Staff Three Weeks After the Policy Opening of COVID-19 Pandemic in China: Deliberate Rumination as Mediator
Authors: Ma Huihui , Zhang Yi , Li Hong , Jiang Tao
Published: September 2024

In the context of the Corona Virus Disease 2019 (COVID-19) pandemic, medical staff have experienced traumatic stress events. Research on post-traumatic growth (PTG) was limited. We aimed to assess the relationship between perceived social support and PTG among medical staff 3 weeks after the policy opening of COVID-19 pandemic in Nanjing, China and explore the mediating roles of deliberate rumination. A multicenter study including a total of 842 medical staff was conducted at two general hospitals from December 10, 2022, to December 25, 2022, in Nanjing, China. SPSS was used for statistical description and univariate analysis, and AMOS was used for structural equation modeling (SEM) to analyze the medicating effect of deliberate social support on PTG. In the SEM, the total effect of perceived social support on PTG was significant (β = .332, 95% CI [0.259, 0.408], p < .001). In addition, deliberate rumination played a mediating role between perceived social support and PTG, and the indirect effect of deliberate rumination between perceived social support and PTG was −.036 (95 % CI [−0.059, −0.018], p < .001). Perceived social support has significant direct and indirect effects on PTG. In the context of major public health emergencies, providing medical staff with more social support and guiding them to reflect positively could help medical staff achieve PTG after experiencing a traumatic event.
Social Inequalities in Loneliness: Disentangling the Contributions of Education, Income, and Occupation
Authors: Beller Johannes
Published: September 2024

Loneliness represents a serious health risk. However, studies investigating social inequalities in loneliness are rare. Thus, the current study investigates which socioeconomic groups are the most affected by loneliness. Data from the population-based German Aging Survey were used ( N = 3,784), with participants being 40+ years old. Education, income, and occupational prestige were used as socioeconomic indicators. It was found that loneliness scores were descriptively higher in groups with lower educational attainment, lower income and lower occupational prestige. In a linear regression analysis, significant socioeconomic differences in loneliness emerged only for income and occupational prestige. Thus, individuals with a low occupational position and those with low income are systematically more affected by loneliness than higher status groups. Material and occupational resources are likely to constitute major socio-structural explanatory variables for loneliness and should be further investigated as such by future studies.
Modeling Organizations’ Responses to Employee Disclosure at Work: An Organizational Economics Approach
Authors: Keays Daniel
Published: September 2024

Employee disclosure refers to the process of revealing personal information about oneself with others in a workplace setting. This type of disclosure also greatly influences organizational culture, policies, and workplace interactions. Modeling such disclosure scenarios using an organizational economics approach addresses communication challenges faced by businesses dealing with the respective disclosure(s). Further, it allows for uncovering the most effective ways to communicate disclosure procedures and policies to employees and employers. This, in turn, will lead to (a) improved corporate training practices for employee disclosure in business communication settings and (b) increased overall productivity measures for organizational members.
Enhancing Anesthesia Education and Clinical Practice: A Comprehensive Review of GASMAN Simulation Software
Authors: Chen Chao , Yang Shengfeng , Xiong Xinglong , Shi Yewei , Zhong Xingfeng , Shi Jing
Published: September 2024

GASMAN software, a simulation tool for inhalational anesthetics’ pharmacokinetics and pharmacodynamics, has become essential in both anesthesia education and clinical practice. This review explores its applications, highlighting its effectiveness in enhancing medical education and its impact on clinical anesthesia management. In educational settings, GASMAN software facilitates a deeper understanding of anesthetic pharmacology through interactive and visual simulations, thereby improving students’ learning outcomes and engagement. Clinically, it aids anesthesiologists in optimizing anesthetic dosing, enhancing patient safety, and supporting real-time decision-making during surgeries. Despite its advantages, GASMAN software faces limitations such as the absence of physiological feedback and the need for continuous data model updates. Future directions include technical enhancements, integration with advanced patient simulators, and broader dissemination through educational partnerships. This review emphasizes the significant contributions of GASMAN software to anesthesia education and clinical practice and suggests pathways for future improvements and wider adoption.
Sexual Dysfunction, Marital Adjustment, and Quality of Life Among Male Persons with Alcohol Dependence Syndrome Attending Tertiary Healthcare Institution in Northeast India: A Cross-Sectional Study
Authors: Sarkar Bubul , Ali Arif , Paul Fayaz Ahmad
Published: September 2024

Background:

Sexual dysfunction is one of the major problems associated with the chronic use of alcohol. Sexual dysfunction is also significantly associated with marital adjustment and quality of life.

Aim and Objectives:

To determine the prevalence of sexual dysfunction and its association with marital adjustment and quality of life among persons with alcohol dependence syndrome (ADS) and to compare with the healthy control group.

Materials and Methods:

The present study used a cross-sectional, comparative, and descriptive research design. A purposive sampling technique was used to select the sample of 128 (64 patients with ADS and 64 healthy control persons) between the ages of 21 and 50, from the Department of Addiction Medicine, LGB Regional Institute of Mental Health (LGBRIMH), Tezpur, Assam. Sociodemographic and clinical data sheet, the Arizona Sexual Experience Scale (ASEX), the Severity of Alcohol Dependence Questionnaire (SDAQ), the Alcohol Use Disorders Identification Test (AUDIT), the International Index of Erectile Dysfunction (IIED), and The Drug Abuse Screening Test scales (DAST) were used.

Results:

The study revealed a higher prevalence of sexual dysfunction in the ADS group (64%) compared to the healthy control group (35.9%) (Chi-square = 46.916; p < .001). Marital satisfaction was significantly lower in the ADS group than in the healthy control group (Fisher’s exact test = 76.932; p < .001). Quality of life was also diminished in the ADS group, particularly in the physical ( t = −5.310; p <.001), social ( t = −4.481; p < .001), and environmental domains ( t = −4.250; p < .001). Furthermore, sexual dysfunction exhibited a significant negative correlation with marital adjustment ( r = −0.676; p < .01) and all domains of quality of life [physical domain ( r = −0.235; p < .001), social domain ( r = −0.383; p < .001), and environmental domain ( r = −0.383; p < .001)].

Conclusion:

The prevalence of sexual dysfunction and erectile dysfunction was high in persons with alcohol dependence syndrome as compared to the healthy control group and it has a relationship with marital adjustment and quality of life. The findings highlight the importance of screening and evaluating sexual dysfunction in individuals with alcohol dependence. Comprehensive pharmacological and nonpharmacological services are warranted to address the unique needs of this population, promoting both recovery from alcohol dependence and improvement in overall quality of life.
Increased CCL2/CCR2 axis promotes tumor progression by increasing M2 macrophages in MYC/BCL2 double-expressor DLBCL
Authors: Kim Sehui , Jeong Hyein , Ahn Hyun Kyung , Han Bogyeong , Lee Ki-Chang , Song Young Keun , Lim Sojung , Yim Jeemin , Koh Jaemoon , Jeon Yoon Kyung
Published: September 2024

The pathogenesis of myelocytomatosis oncogene (MYC) and B-cell lymphoma 2 (BCL2) double-expressor diffuse large B-cell lymphoma (DE-DLBCL) remains unclear. To investigate how MYC and BCL2 contribute to tumor aggressiveness, we analyzed tumors from 14 patients each with DE-DLBCL and non–DE-DLBCL using whole transcriptome sequencing. Validation was performed using publicly available data sets, tumor tissues from 126 patients, DLBCL cell lines, and a syngeneic mouse lymphoma model. Our transcriptome analysis revealed significantly elevated messenger RNA levels of C-C motif chemokine ligand 2 (CCL2) and C-C chemokine receptor type 2 (CCR2) in DE-DLBCLs when compared with non–DE-DLBCLs (adjusted P value < .05). Transcriptomic analysis of public data sets and immunohistochemistry corroborated these findings, indicating increased levels of M2 macrophages but a reduction in T-cell infiltration in DE-DLBCLs when compared with non–DE-DLBCLs (all P < .05). CCR2 expression was observed mainly in tumor-infiltrating macrophages and not in DLBCL cells. Increased expression of CCL2 and CCR2 was significantly associated with a poor prognosis in patients with DLBCL. In the in vitro analyses, MYChigh/BCL2high DLBCL cells showed higher CCL2 expression and secretion than MYClow/BCL2low cells. MYC and BCL2 increased CCL2 expression and secretion by upregulation of nuclear factor κB p65 in DLBCL cells, and CCL2 promoted M2 polarization of macrophages. In a mouse lymphoma model, CCL2 contributed to the immunosuppressive microenvironment and tumor growth of MYChigh/BCL2high tumors. We demonstrated that the increased CCL2/CCR2 axis confers aggressiveness to DE-DLBCL by increasing M2 polarization and can be a potential therapeutic target.
Identification of primary mediastinal B-cell lymphomas with higher clonal dominance and poorer outcome using 5′RACE
Authors: Camus Vincent , Viennot Mathieu , Viailly Pierre-Julien , Drieux Fanny , Veresezan Elena-Liana , Bobée Victor , Rainville Vinciane , Bohers Elodie , Sesques Pierre , Haioun Corinne , Durot Eric , Bayaram Michael , Rossi Cédric , Martin Laurent , Penther Dominique , Kaltenbach Sophie , Bruneau Julie , Paillassa Jérôme , Tournilhac Olivier , Gower Nicolas , Willaume Alexandre , Antier Chloé , Renaud Loïc , Lévêque Emilie , Decazes Pierre , Becker Stéphanie , Tonnelet David , Gaulard Philippe , Tilly Hervé , Molina Thierry Jo , Traverse-Glehen Alexandra , Donzel Marie , Ruminy Philippe , Jardin Fabrice
Published: September 2024

There is a scarcity of data on the tumor B-cell receptor (BCR) repertoire and lymphoid microenvironment in primary mediastinal B-cell lymphoma (PMBL). We applied 5ʹ rapid amplification of complimentary DNA ends (5′RACE) to tumor RNA samples from 137 patients with PMBL with available gene expression profiling and next-generation sequencing data. We obtained 5′RACE results for 75 of the 137 (54.7%) patients with the following clinical characteristics: median age (range), 33 years (18-64); female, 53.3%; performance status score 0 to 1, 86.7%; stage I to II, 57.3%; first-line treatment with anti-CD20 plus doxorubicin-based chemotherapy, 100%. Among the 60 biopsies that expressed a productive BCR, we highlighted a strong somatic hypermutation profile, defined as <98% identity to the germ line sequence, with 58 (96.7%) patients carrying mutated IgVH. We then identified a subgroup of 12 of the 75 patients (16%) with a worse prognosis (progression-free survival [PFS]: hazard ratio [HR], 17; overall survival [OS]: HR, 21) that was associated with the highest clonal dominance (HCD) status, defined as the dominant clonotype representing >81.1% and >78.6% of all complementarity-determining region 3 sequences for IgVH and IgVL, respectively. When compared with other patients, this subgroup had similar clinical characteristics but a greater median allele frequency for all somatic variants, a decreased BCR diversity, and greater expression of PDL1/PDL2 and MS4A1 genes, suggesting greater tumoral infiltration. We confirmed this poorer prognosis in a multivariate model and in an independent validation cohort in which 6 of 37 (16%) PMBL patients exhibited HCD (PFS: HR, 12; OS: HR, 17).
Antithrombotic efficacy and bleeding risks of vaccine-induced immune thrombotic thrombocytopenia treatments
Authors: Leung Halina H. L. , Ahmadi Zohra , Lee Brendan , Casey John , Ratnasingam Sumita , McKenzie Steven E. , Perdomo Jose , Chong Beng H.
Published: September 2024

Current guidelines for treating vaccine-induced immune thrombotic thrombocytopenia (VITT) recommend nonheparin anticoagulants and IV immunoglobulin (IVIg). However, the efficacy of these treatments remains uncertain due to case studies involving small patient numbers, confounding factors (eg, concurrent treatments), and a lack of animal studies. A recent study proposed danaparoid and heparin as potential VITT therapies because of their ability to disrupt VITT IgG-platelet factor 4 (PF4) binding. Here, we examined the effects of various anticoagulants (including unfractionated [UF] heparin, danaparoid, bivalirudin, fondaparinux, and argatroban), IVIg, and the FcγRIIa receptor-blocking antibody, IV.3. Our investigation focused on VITT IgG-PF4 binding, platelet activation, thrombocytopenia, and thrombosis. Danaparoid, at therapeutic doses, was the sole anticoagulant that reduced VITT IgG-PF4 binding, verified by affinity-purified anti-PF4 VITT IgG. Although danaparoid and high-dose UF heparin (10 U/mL) inhibited platelet activation, none of the anticoagulants significantly affected thrombocytopenia in our VITT animal model and all prolonged bleeding time. IVIg and all anticoagulants except UF heparin protected the VITT mice from thrombosis. Direct FcγRIIa receptor inhibition with IV.3 antibody is an effective approach for managing both thrombosis and thrombocytopenia in the VITT mouse model. Our results underscore the necessity of animal model investigations to inform and better guide clinicians on treatment choices. This study provides compelling evidence for the development of FcγRIIa receptor blockers to prevent thrombosis in VITT and other FcγRIIa-related inflammatory disorders.
A prospective study of the association between varicoceles and semen quality in men with infertility
Authors: Ogunjimi Moses Adebisi , Abudu Olalekan Abdul-Rafiu , Jeje Emmanuel Ajibola , Ojewola Rufus Wale , Arogundade Rasheed Ajani
Published: September 2024

Background

Male infertility is a global problem, and varicoceles are a common and treatable cause of male infertility. This study prospectively evaluated the effects of varicoceles on the fertility status and potential among Nigerian men. The consequences of the presence, location, and grades of varicoceles on the fertility status of infertile men with varicoceles were determined using a Doppler scrotal ultrasound scan and their seminal fluid parameters.

Methods

One hundred infertile males with clinical varicoceles (study group) and 100 infertile males without varicocele (control group) were recruited. Varicoceles were confirmed/excluded and graded with an ultrasound scan in each subject. They also all had a seminal fluid analysis to measure their fertility potential. The findings were compared and correlated in the two groups.

Results

Most subjects in the study group (67%) had bilateral varicoceles, 31% had isolated left varicoceles, and only 2% had isolated right varicoceles. The majority of the participants (61%) in the study group had secondary infertility, while the majority (63%) in the control group had primary infertility (p = 0.001). There were significant increases in the prevalence of azoospermia (p = 0.008) and oligospermia (p = 0.030) with the higher grades of left varicoceles.

Conclusion

Bilateral varicoceles were significantly present in males with infertility in the study group. Varicoceles were more common in males with secondary infertility, and higher grades of varicoceles were significantly more associated with azoospermia and severe oligospermia. We recommend the routine use of ultrasound scans to diagnose varicoceles for the optimal management of infertile male patients.
The storage time of cryopreserved human spermatozoa does not affect pathways involved in fertility
Authors: Stigliani Sara , Amaro Adriana , Reggiani Francesco , Maccarini Elena , Massarotti Claudia , Lambertini Matteo , Anserini Paola , Scaruffi Paola
Published: September 2024

Background

Cryopreservation of human spermatozoa is a widely used technique in the assisted reproduction technology laboratory for the storage of gametes for later use, for the fertility preservation and for sperm donation programs. Cryopreservation can cause damage to membrane, cytoskeletal, acrosome and increased oxidative stress, sperm DNA damage and transcriptome changes. To assess the impact of storage time on the transcriptome of frozen human spermatozoa, semen samples were collected from 24 normospermic donors of whom 13 had cryostored semen for a short-time (1 week) and 11 had cryostored semen for a long-time (median 9 years).

Results

RNA was extracted from each frozen-thawed sperm sample, randomized in pools, and analyzed by microarrays. Five transcripts were in higher abundance in the long-time respect to the short-time storage group. Functional annotation enrichment disclosed that that the length of cryostorage has no effect on critical pathways involved in sperm physiology and function.

Conclusions

The storage time of cryopreserved human spermatozoa does not affect pathways involved in fertility.
Analysis of genotyping data reveals the unique genetic diversity represented by the breeds of sheep native to the United Kingdom
Authors: Kerr Eleanor , Marr Melissa M. , Collins Lauren , Dubarry Katie , Salavati Mazdak , Scinto Alissa , Woolley Shernae , Clark Emily L.
Published: September 2024

Background

Sheep breeds native to the United Kingdom exhibit a striking diversity of different traits. Some of these traits are highly sustainable, such as seasonal wool shedding in the Wiltshire Horn, and are likely to become more important as pressures on sheep production increase in coming decades. Despite their clear importance to the future of sheep farming, the genetic diversity of native UK sheep breeds is poorly characterised. This increases the risk of losing the ability to select for breed-specific traits from native breeds that might be important to the UK sheep sector in the future. Here, we use 50 K genotyping to perform preliminary analysis of breed relationships and genetic diversity within native UK sheep breeds, as a first step towards a comprehensive characterisation. This study generates novel data for thirteen native UK breeds, including six on the UK Breeds at Risk (BAR) list, and utilises existing data from the publicly available Sheep HapMap dataset to investigate population structure, heterozygosity and admixture.

Results

In this study the commercial breeds exhibited high levels of admixture, weaker population structure and had higher heterozygosity compared to the other native breeds, which generally tend to be more distinct, less admixed, and have lower genetic diversity and higher kinship coefficients. Some breeds including the Wiltshire Horn, Lincoln Longwool and Ryeland showed very little admixture at all, indicating a high level of breed integrity but potentially low genetic diversity. Population structure and admixture were strongly influenced by sample size and sample provenance – highlighting the need for equal sample sizes, sufficient numbers of individuals per breed, and sampling across multiple flocks. The genetic profiles both within and between breeds were highly complex for UK sheep, reflecting the complexity in the demographic history of these breeds.

Conclusion

Our results highlight the utility of genotyping data for investigating breed diversity and genetic structure. They also suggest that routine generation of genotyping data would be very useful in informing conservation strategies for rare and declining breeds with small population sizes. We conclude that generating genetic resources for the sheep breeds that are native to the UK will help preserve the considerable genetic diversity represented by these breeds, and safe-guard this diversity as a valuable resource for the UK sheep sector to utilise in the face of future challenges.
Structural validation of two person-centred practice inventories PCPI-S and PCPI-C - French version
Authors: Mabire Cedric , Piccot-Crezollet Marie , Tyagi Vaibhav , McCormack Brendan , Pellet Joanie
Published: September 2024

Background

The shift towards person-centred care has become integral in achieving high-quality healthcare, focusing on individual patient needs, preferences, and values. However, existing instruments for measuring person-centred practice often lack theoretical underpinnings and comprehensive assessment. The Person-centred Practice Inventory – Staff (PCPI-S) and the Person-centred Practice Inventory – Care (PCPI-C) were developed in English to measure clinicians’ and patients’ experience of person-centred practice. The aim of this study was to investigate the psychometric properties of the French version of the PCPI-S and PCPI-C.

Methods

A multi-centred cross-sectional study was conducted in six hospitals in French-speaking Switzerland. Construct validity of the PCPI-S and the PCPI-C was evaluated by using confirmatory factor analysis and McDonald’s Omega coefficient was used to determine the internal consistency.

Results

A sample of 558 healthcare professionals and 510 patients participated in the surveys. Psychometric analyses revealed positive item scores and acceptable factor loadings, demonstrating the meaningful contribution of each item to the measurement model. The Omega coefficient indicated acceptable to excellent internal consistency for the constructs. Model fit statistics demonstrated good model fit for the PCPI-S and PCPI-C.

Conclusions

The findings support the construct validity and internal consistency of the PCPI-S and PCPI-C in assessing person-centred practice among healthcare professionals and patients in French-speaking Switzerland. This validation offers valuable tools for evaluating person-centred care in hospital settings.
Surveillance of tick-borne pathogens in domestic dogs from Chad, Africa
Authors: Haynes Ellen , Garrett Kayla B. , Grunert Ryan K. A. , Bryan John A. , Sidouin Metinou , Oaukou Philip Tchindebet , Ngandolo Bongo Nare Richard , Yabsley Michael J. , Cleveland Christopher A.
Published: September 2024

Background

Tick-borne pathogens are understudied among domestic animals in sub-Saharan Africa but represent significant threats to the health of domestic animals and humans. Specifically, additional data are needed on tick-borne pathogens in Chad, Africa. Surveillance was conducted among domestic dogs in Chad for selected tick-borne pathogens to measure (1) the prevalence of antibodies against Anaplasma spp., Borrelia burgdorferi, and Ehrlichia spp.; (2) the prevalence of infections caused by Hepatozoon spp., Ehrlichia canis, Anaplasma platys, and Babesia spp.; and (3) associations of pathogens with demographic, spatial, and temporal factors. Blood samples were collected from domestic dogs at three time points (May 2019, November 2019, June 2020) across 23 villages in southern Chad.

Results

Of the 428 dogs tested with the IDEXX SNAP 4Dx test in May 2019, 86% (n = 370, 95% CI = 83–90%) were positive for antibodies to Ehrlichia spp., 21% (n = 88, 95% CI = 17–25%) were positive for antibodies to Anaplasma spp., and 0.7% (n = 3, 95% CI = 0.1–2%) were positive for antibodies to Borrelia burgdorferi. Four different pathogens were detected via PCR. Hepatozoon spp. were most commonly detected (67.2–93.4%, depending on the time point of sampling), followed by E. canis (7.0-27.8%), A. platys (10.1–22.0%), and Babesia vogeli (0.4–1.9%). Dogs were coinfected with up to three pathogens at a single time point, and coinfections were most common in May 2019 compared to November 2019 and May 2020.

Conclusions

Overall, this study provides new data about the epidemiology of tick-borne pathogens in domestic dogs in Chad, with potential implications for dog and human health.
Mechanism of norcantharidin intervention in gastric cancer: analysis based on antitumor proprietary Chinese medicine database, network pharmacology, and transcriptomics
Authors: Zhai Yiyan , Zhang Fanqin , Zhou Jiying , Qiao Chuanqi , Jin Zhengsen , Zhang Jingyuan , Wu Chao , Shi Rui , Huang Jiaqi , Gao Yifei , Guo Siyu , Wang Haojia , Chai Keyan , Zhang Xiaomeng , Wang Tieshan , Sheng Xiaoguang , Liu Xinkui , Wu Jiarui
Published: September 2024

Background

Combining antitumor proprietary Chinese medicine (pCm) with radiotherapy and chemotherapy can effectively improve tumor cure rates and enhance patients’ quality of life. Gastric cancer (GC) severely endangers public health. Despite satisfactory therapeutic effects achieved by using antitumor pCm to treat GC, its underlying mechanism remains unclear.

Objective

To integrate existing research data, construct a database of antitumor pCm, and study the intervention mechanisms in GC by focusing on their monomer components.

Methods

We constructed an antitumor pCm database based on China’s medical insurance catalog, and employed network pharmacology, molecular docking methods, cell experiments, transcriptomics, and bioinformatics to investigate the intervention mechanisms of effective pCm components for GC.

Results

The study built an antitumor pCm database including 55 pCms, 171 Chinese herbal medicines, 1955 chemical components, 2104 targets, and 32 disease information. Network pharmacology and molecular docking technology identified norcantharidin as an effective component of antitumor pCm. In vitro experiments showed that norcantharidin effectively inhibited GC cell proliferation, migration, and invasion; blocked the G2/M cell cycle phase; and induced GC cell apoptosis. Transcriptomic results revealed that norcantharidin affected biological processes, such as cell adhesion, migration, and inflammatory responses by influencing PI3K-AKT, NF-κB, JAK-STAT, TNF-α signaling pathways, and EMT-related pathways. Core molecules of norcantharidin involved in GC intervention include SERPINE1, SHOX2, SOX4, PRDM1, TGFR3, TOX, PAX9, IL2RB, LAG3, and IL15RA. Additionally, the key target SERPINE1 was identified using bioinformatics methods.

Conclusion

Norcantharidin, as an effective component of anti-tumor pCm, exerts its therapeutic effects on GC by influencing biological processes such as cell adhesion, migration, and inflammation. This study provides a foundation and research strategy for the post-marketing re-evaluation of antitumor pCms.
Neonatal Marfan syndrome: a case report of a novel fibrillin 1 mutation, with genotype-phenotype correlation and brief review of the literature
Authors: Pugnaloni Flaminia , De Rose Domenico Umberto , Digilio Maria Cristina , Magliozzi Monia , Braguglia Annabella , Valfrè Laura , Toscano Alessandra , Dotta Andrea , Di Pede Alessandra
Published: September 2024

Background

Neonatal Marfan syndrome (nMFS) is a rare condition characterized by severe phenotype and poor prognosis. nMFS is caused by mutations in a specific region of the fibrillin 1 gene (FBN1). Prompt recognition of typical signs of neonatal presentation, such as characteristic facial anomalies with senile appearance, arthrogryposis, and campto-arachnodactyly, is fundamental for performing an early cardiological examination. This usually reveals rapidly progressive cardiovascular disease due to severe atrioventricular valve dysfunction.

Case presentation

Herein, we report the case of an early-onset cardiac failure in a neonate with Marfan syndrome, with a brief review of the literature of cases with cardiac involvement in neonatal age. Clinical exome sequencing identified the novel heterozygous de novo missense variant c.3152T > G in FBN1 gene (NM_000138.4), causing the aminoacidic change p.Phe1051Cys. Phenotype-genotype correlation led to a multidisciplinary diagnostic and management workflow.

Conclusion

The prompt recognition of a typical phenotype such as that of Marfan syndrome should lead to a detailed evaluation and close follow-up of cardiac morphology and function. Indeed, multi-disciplinary evaluation based on genotype-phenotype correlations of nMFS cases is essential to finding out the best medical and surgical approach, predicting the relevant impact on patient prognosis, and adequately counseling their families.
Isolated external jugular thrombophlebitis secondary to acute pharyngitis: a case report and a review of the literature
Authors: Ezeh Uche C. , Tesema Naomi , Hasnie Sukaina , Kahn Philip J. , April Max M.
Published: September 2024

Background

External Jugular Thrombophlebitis (EJT) is a rare clinical phenomenon with few reports in the literature, especially in the pediatric population. This is a report of an unusual case of right-sided EJT in a pediatric patient secondary to acute pharyngitis with sinusitis most prominent on the left side.

Case presentation

A 13-year-old presented to the emergency department with worsening upper respiratory infectious (URI) symptoms and facial swelling, cough, throat pain, and emesis. The patient had traveled to Switzerland and received amoxicillin for strep throat 6 weeks before this hospitalization. Physical examination revealed nasal purulence, allodynia over the right side of the face without overlying erythema, and oropharyngeal exudate. CT scan revealed left-sided predominate sinusitis and right external jugular vein thrombosis. Blood cultures confirmed the presence of group A streptococcus infection. Treatment included IV antibiotics, non-steroidal anti-inflammatory drugs (NSAIDs), IV steroids, and anticoagulation. Follow-up imaging demonstrated improvement in thrombosis, cellulitis, and sinus disease. The patient was discharged on antibiotics for 6 weeks and anticoagulation for 10 weeks. Follow-up imaging at 6 months revealed no EJT, and medications were discontinued.

Conclusions

EJT is a rare condition, and to our knowledge, no reports of EJT with sinusitis most pronounced on the contralateral side have been published. Physicians will benefit from noting clinical signs of EJT such as facial edema, headache, erythema, and palpable neck mass, especially if these symptoms occur with URI symptoms refractory to treatment. The use of anticoagulation is controversial for internal jugular vein thrombosis, and while no guidelines for EJT exist, anticoagulation is likely not necessary save for severe complications.
Anisakis extracellular vesicles elicit immunomodulatory and potentially tumorigenic outcomes on human intestinal organoids
Authors: Bellini Ilaria , Scribano Daniela , Ambrosi Cecilia , Chiovoloni Claudia , Rondón Silvia , Pronio Annamaria , Palamara Anna Teresa , Pietrantoni Agostina , Kashkanova Anna , Sandoghdar Vahid , D’Amelio Stefano , Cavallero Serena
Published: September 2024

Background

Anisakis spp. are zoonotic nematodes causing mild to severe acute and chronic gastrointestinal infections. Chronic anisakiasis can lead to erosive mucosal ulcers, granulomas and inflammation, potential tumorigenic triggers. How Anisakis exerts its pathogenic potential through extracellular vesicles (EVs) and whether third-stage infective larvae may favor a tumorigenic microenvironment remain unclear.

Methods

Here, we investigated the parasite's tumorigenic and immunomodulatory capabilities using comparative transcriptomics, qRT-PCR and protein analysis with multiplex ELISA on human intestinal organoids exposed to Anisakis EVs. Moreover, EVs were characterized in terms of shape, size and concentration using classic TEM, SEM and NTA analyses and advanced interferometric NTA.

Results

Anisakis EVs showed classic shape features and a median average diameter of around 100 nm, according to NTA and iNTA. Moreover, a refractive index of 5–20% of non-water content suggested their effective biological cargo. After treatment of human intestinal organoids with Anisakis EVs, an overall parasitic strategy based on mitigation of the immune and inflammatory response was observed. Anisakis EVs impacted gene expression of main cytokines, cell cycle regulation and protein products. Seven key genes related to cell cycle regulation and apoptosis were differentially expressed in organoids exposed to EVs. In particular, the downregulation of EPHB2 and LEFTY1 and upregulation of NUPR1 genes known to be associated with colorectal cancer were observed, suggesting their involvement in tumorigenic microenvironment. A statistically significant reduction in specific mediators of inflammation and cell-cycle regulation from the polarized epithelium as IL-33R, CD40 and CEACAM1 from the apical chambers and IL-1B, GM-CSF, IL-15 and IL-23 from both chambers were observed.

Conclusions

The results here obtained unravel intestinal epithelium response to Anisakis EVs, impacting host’s anthelminthic strategies and revealing for the first time to our knowledge the host-parasite interactions in the niche environment of an emerging accidental zoonosis. Use of an innovative EV characterization approach may also be useful for study of other helminth EVs, since the knowledge in this field is very limited.

Graphical Abstract
The Israeli anesthesiology workforce crisis: a reassessment survey
Authors: Wimpfheimer Ariel , Ginosar Yehuda , Fein Shai , Goldberger Esty , Weissman Charles ,   the Israel Anesthesiology Workforce Study Group, Abd-Al-Halim Haled , Abu-Rais Hakeem , Berkenstadt Chaim , Chernoy Ilya , Armaly Maruan , Duvdivani Yaakov , Eidelman Leonid , Fine Shai , Fredman Brian , Gadulov Yulia , Goldik Zeev , Gozal Yaakov , Haituv Zoya , Izakson Alex , Katz Yaakov , Matot Idit , Mubada Noam , Pizov Reuven , Raz Aeyal , Revaz Gefen , Reznikof Igor , Rigzny Nogzar , Rudin Michael , Rukinglass Vladimir , Sabatnitzki Albert , Segal Eran , Siton Eric , Somri Mustafa , Tome Riad , Turban Jacob , Weksler Nathan , Wilner Dafna , Witchelevsky Yossi , Zlotnik Alex
Published: September 2024

Background

Anesthesiologists provide crucial anesthesiology services in the operating room and non-operating room locations. Combined with an aging and growing Israeli population, there is an increasing demand for anesthesiology services. A previous study performed in 2005 showed that most anesthesiologists are immigrant physicians with few Israeli medical school graduates. Since then, physician immigration decreased, many have retired and demand for anesthesia services has increased while insufficient numbers of new anesthesiologists were trained, leading to a shortage, limiting surgeries and other procedures in many hospitals. The present study examined the composition of the Israeli anesthesiology workforce in 2021and compared it to the 2005 workforce.

Methods

A cross-sectional survey of demographic and professional information about each Israeli hospital anesthesiologists was solicited from 34 anesthesiology department chairs responsible for 36 Israeli acute care hospitals.

Results

There are 1313 anesthesiologists in the 36 hospitals, resulting in a ratio of 14.2 anesthesiologists per 100,000 population. 22.6% of anesthesiologists will reach retirement age over the next ten years. The proportion of female anesthesiologists was 28.7%. While Israeli medical school graduates increased to 18.1% from 12.2% in 2005, non-Israeli citizens and non-permanent residents comprised 8.5% of the workforce.

Conclusions

Despite growth in the ratio of anesthesiologists per population, a workforce shortage is expected to worsen over the next ten years due to retirements, shortened call hours, and the Yatziv reform which bans graduates of certain overseas medical schools from obtaining Israeli Medical Licenses. The current workforce has compensated for the existing shortage of anesthesiologists by enlisting non-Israeli trainees from overseas. Yet, it is crucial to maintain and enlarge the local Israeli workforce to forestall a worsening shortage.
Possibility of the optimum monitoring and evaluation (M&E) production frontier for risk-informed health governance in disaster-prone districts of West Bengal, India
Authors: Mukherjee Moumita , Batta Anuj
Published: September 2024

An efficient M&E system in public healthcare is crucial for achieving universal health coverage in low- and middle-income countries, especially when the need for service remains unmet due to the exposure of the population to disaster risks and uncertainties. Current research has conducted exploratory and predictive analyses to estimate the determinants of sustainable M&E solutions for ensuring uninterrupted access during and after disasters. The aim was to estimate the efficiency of reaching a higher M&E production frontier via the Cobb‒Douglas model and stochastic frontier model as the basic theoretical and empirical frameworks. The research followed a deductive approach and used a stratified purposive sampling method to collect data from different layers of health and disaster governance in a flood-prone rural setting in the Malda, South 24 Parganas and Purulia districts in West Bengal, India. The present mixed-method study revealed multiple challenges in healthcare seeking during disasters and how a well-structured M&E system can increase system readiness to combat these challenges. The stochastic frontier model estimated the highest M&E frontier producing the most attainable M&E effectiveness through horizontal convergence between departments, enhanced coordination, the availability of frontline health workers at health centers, the adoption of learned innovation and the outsourcing of the evaluation component to external evaluators to improve M&E process quality. Although the study has several limitations, it shows the potential to increase technical and allocative efficiency through building skills in innovative techniques and applying them in process implementation. In the future, research on strategy improvement followed by real-world evidence-based policy advocacy is needed to increase the impact of M&E on access to healthcare services.
Deep Learning Features Can Improve Radiomics-Based Prostate Cancer Aggressiveness Prediction
Authors: Rodrigues Nuno M. , Almeida José Guilherme de , Rodrigues Ana , Vanneschi Leonardo , Matos Celso , Lisitskaya Maria V. , Uysal Aycan , Silva Sara , Papanikolaou Nickolas
Published: September 2024

PURPOSE

Emerging evidence suggests that the use of artificial intelligence can assist in the timely detection and optimization of therapeutic approach in patients with prostate cancer. The conventional perspective on radiomics encompassing segmentation and the extraction of radiomic features considers it as an independent and sequential process. However, it is not necessary to adhere to this viewpoint. In this study, we show that besides generating masks from which radiomic features can be extracted, prostate segmentation and reconstruction models provide valuable information in their feature space, which can improve the quality of radiomic signatures models for disease aggressiveness classification.

MATERIALS AND METHODS

We perform 2,244 experiments with deep learning features extracted from 13 different models trained using different anatomic zones and characterize how modeling decisions, such as deep feature aggregation and dimensionality reduction, affect performance.

RESULTS

While models using deep features from full gland and radiomic features consistently lead to improved disease aggressiveness prediction performance, others are detrimental. Our results suggest that the use of deep features can be beneficial, but an appropriate and comprehensive assessment is necessary to ensure that their inclusion does not harm predictive performance.

CONCLUSION

The study findings reveal that incorporating deep features derived from autoencoder models trained to reconstruct the full prostate gland (both zonal models show worse performance than radiomics only models), combined with radiomic features, often lead to a statistically significant increase in model performance for disease aggressiveness classification. Additionally, the results also demonstrate that the choice of feature selection is key to achieving good performance, with principal component analysis (PCA) and PCA + relief being the best approaches and that there is no clear difference between the three proposed latent representation extraction techniques.
Familial Nonautoimmune Hyperthyroidism Due to a TSH Receptor Gene Pathogenic Variant
Authors: Takahashi Sawako , Nishihara Eijun , Fukata Shuji , Miyauchi Akira , Akamizu Takashi
Published: September 2024

Familial nonautoimmune hyperthyroidism (NAH) is a rare type of autosomal dominant hyperthyroidism caused by constitutively active pathogenic variants of the thyrotropin receptor (TSHR) gene. Although affected family members present with varied levels of hyperthyroid features, even when the same pathogenic variant is present, total thyroidectomy followed by radioiodine therapy is recommended for long-term management. Herein, we present the case of an 18-year-old proband and her family members with NAH (TSHR-I640V), who presented with diverse thyroid dysfunctions: fluctuations between euthyroid and subclinical hyperthyroidism, mild hyperthyroidism, and overt hyperthyroidism. Almost all affected adult family members, except the proband, showed no progression of hyperthyroidism or thyroid enlargement. A family history of thyrotropin receptor antibodies (TRAb)-negative hyperthyroidism is important for the identification of NAH in adults before TSHR genetic testing can be performed. Ablative therapy is not necessary when familial NAH presents with late-onset mild hyperthyroidism without coexisting diseases.
Rewriting the Literary Past: D. H. Lawrence and Geoff Dyer’s Antibiography
Authors: Koenig Andrew
Published: September 2024

Why do memoirists, in order to find themselves, find it necessary to rewrite their favorite authors? This article explores this question by analyzing D. H. Lawrence and Geoff Dyer and tracing Dyer’s conflicted attitude to memoir and rewriting back to Lawrence, specifically his Study of Thomas Hardy. If by now the book market is awash in antibiographical rewrites, that is because rewriting first asserted itself as a contrarian impulse, a radically different way of thinking about the canon that has become second nature.
Beyond Chatbot-K: On Large Language Models, “Generative AI,” and Rise of Chatbots—An Introduction
Authors: Goodlad Lauren M. E. , Stone Matthew
Published: September 2024

This essay introduces the history of the “generative AI” paradigm, including its underlying political economy, key technical developments, and sociocultural and environmental effects. In concert with this framing it discusses the articles, thinkpieces, and reviews that make up part 1 of this two-part special issue (along with some of the content for part 2). Although large language models (LLMs) are marketed as scientific wonders, they were not designed to function as either reliable interactive systems or robust tools for supporting human communication or information access. Their development and deployment as commercial tools in a climate of reductive data positivism and underregulated corporate power overturned a long history in which researchers regarded chatbots as “misaligned” affordances for safe or reliable public use. While the technical underpinnings of these much-hyped systems are guarded as proprietary secrets that cannot be shared with researchers, regulators, or the public at large, there is ample evidence to show that their development depends on the expropriation and privatization of human-generated content (much of it under copyright); the expenditure of enormous computing resources (including energy, water, and scarce materials); and the hidden exploitation of armies of human workers whose low-paid and high-stress labor makes “AI” seem more like human “intelligence” or communication. At the same time, the marketing of chatbots propagates a deceptive ideology of “frictionless knowing” that conflates a person's ability to leverage a tool for producing an output with that person's active understanding and awareness of the relevant information or truth claims therein. By contrast, the best digital infrastructures for human writing enable human users by amplifying and concretizing their interactive role in crafting trains of contemplation and rendering this situated experience in shareable form. The essay concludes with reflections on alternative pathways for developing AI—including communicative tools—in the public interest.
Build Word Gyms, Not Word Factories
Authors: Booten Kyle
Published: September 2024

This article argues that it is essential to design algorithmic systems that help us think instead of thinking for us. The aim of the article is to give some sense of how broad and diverse is the design space of interactive systems that use computation to challenge writers to be stronger and more limber.