bluuebunny/crossref_metadata_2025 huggingface dataset:
When epistemologies collide: Data science epistemology and organizational theory and research
Authors: Somers Mark John
Published: January 2025

This paper analyzes how enthusiasm for data science methods in organization science has masked divergences between data science and organization science epistemologies and the likely consequences of adopting some or all of the precepts of data science epistemology on the future direction of organization science theory and research. Possible outcomes are framed in terms of three scenarios: marginalization of data science within organization science, integration of data science and organization science epistemologies and methodologies, and bifurcation with some organization science scholars affirming the current epistemology and others adopting data science epistemology and methods. The paper concludes with suggestions to shape the conversations needed to set a path for the future of OS theory and research.
Pervasive horizontal transmission of Wolbachia in natural populations of closely related and widespread tropical skipper butterflies
Authors: Ribeiro Pedro , Butenko Anzhelika , Linke Daniel , Ghanavi Hamid Reza , Meier Joana Isabel , Wahlberg Niklas , Matos-Maraví Pável
Published: January 2025

Background

The endosymbiotic relationship between Wolbachia bacteria and insects has been of interest for many years due to their diverse types of host reproductive phenotypic manipulation and potential role in the host’s evolutionary history and population dynamics. Even though infection rates are high in Lepidoptera and specifically in butterflies, and reproductive manipulation is present in these taxa, less attention has been given to understanding how Wolbachia is acquired and maintained in their natural populations, across and within species having continental geographical distributions.

Results

We used whole genome sequencing data to investigate the phylogenetics, demographic history, and infection rate dynamics of Wolbachia in four species of the Spicauda genus of skipper butterflies (Lepidoptera: Hesperiidae), a taxon that presents sympatric and often syntopic distribution, with drastic variability in species abundance in the Neotropical region. We show that infection is maintained by high turnover rates driven mainly by pervasive horizontal transmissions, while also presenting novel cases of double infection by distantly related supergroups of Wolbachia in S. simplicius.

Conclusions

Our results suggest that Wolbachia population dynamics is host species-specific, with genetic cohesiveness across wide geographical distributions. We demonstrate that low coverage whole genome sequencing data can be used for an exhaustive assessment of Wolbachia infection in natural populations of butterflies, as well as its dynamics in closely related host species. This ultimately leads to a better understanding of the endosymbiotic population dynamics of Wolbachia and its effects on the host’s biology and evolution.
Analysis of the MYB gene family in tartary buckwheat and functional investigation of FtPinG0005108900.01 in response to drought
Authors: Li Jinbo , Yang Xin , Tian Bianling , Tian Tian , Meng Yu , Liu Fei
Published: January 2025

Tartary buckwheat (Fagopyrum tataricum) is an important crop used for edible food and medicinal usage. Drought annually brings reduction in crop yield and quality, causing enormous economic losses. Transcription factors are often involved in the regulation of plant responses to environmental stresses. In this study, we identified 233 MYB transcription factors in tartary buckwheat and classified them into 13 groups, including 1R, R2R3, 3R, 4R types. Gene structure and conserved motifs of these 233 FtMYBs suggested the relative conservation of these FtMYBs within each group. There is strong collinearity within the genomes of F. tataricum, with identifying syntenic gene pairs of FtMYB. Further, the expansion of FtMYB genes was attributed to whole genome duplication. The enrichment analysis of cis-acting elements in the FtMYB genes indicated that FtMYBs may participate in abiotic stress responses. The transcriptional changes of FtMYB genes in tartary buckwheat were then investigated using public data and qPCR. A number of FtMYB genes exhibited apparent transcript levels in the detected tissues and most of them disturbed their expression after the treatment of PEG6000 or natural treatment of tartary buckwheat seedlings. Some of the FtMYB genes showed a similar expression trend with qPCR validation. FtMYB gene FtPinG0005108900.01 were shown to activated by PEG6000 and natural drought treatment, and its encoded protein localizes to nucleus, revealing it as a typical transcription factor. Overexpression of FtPinG0005108900.01 increase the drought tolerance, and transcriptome analysis indicated that lignin synthesis other than flavonoid biosynthesis pathway was activated in the overexpressing plants following drought treatment. Our results provided detailed evolution and comparative genomic information of FtMYBs in tartary buckwheat and dissected the function of a FtMYB gene FtPinG0005108900.01 in response to drought.
A thematic analysis of UK COVID-19 vaccine hesitancy discussions on Twitter
Authors: Jameel Reeshma , Greenfield Sheila , Lavis Anna
Published: January 2025

Background

Following UK approval of the Pfizer-BioNTech and Oxford-AstraZeneca vaccines on 2/12/20 and 30/12/20 respectively, discussions about them emerged on the social media platform Twitter, (now ‘X’). Previous research has shown that Twitter/ X is used by the UK public to engage with public health announcements and that social media influences public opinions of vaccines, including COVID-19 vaccines, globally. This study explored discussions on Twitter posted in response to the UK government’s posts introducing the Pfizer-BioNTech and Oxford-AstraZeneca vaccines. The aim was to investigate vaccine hesitant views, and thereby identify barriers and facilitators to COVID-19 vaccine uptake in the UK.

Methods

Online ethnography was used to collect responses (‘tweet replies’) to 14 Twitter posts published by officials or departments of the UK government on the dates the Pfizer-BioNTech and Oxford-AstraZeneca vaccines received approval from the Medicines and Healthcare products Regulatory Agency (2/12/20 and 30/12/20, respectively). 16,508 responses were collected and those expressing vaccine hesitancy were analysed using reflexive thematic analysis.

Results

Three themes that underpinned Twitter posters’ vaccine hesitancy were identified: (1) Concerns about vaccine development and safety, (2) Information, misinformation and disinformation, (3) Distrust: Politics and ‘Big Pharma’. From these themes, eight barriers and eight facilitators to UK COVID-19 vaccine uptake were identified.

Conclusion

This paper highlights key obstacles to COVID-19 vaccine acceptance in the UK based on views from Twitter and contributes to the emerging literature on the relationship between social media and the public response to COVID-19 vaccines. In so doing, this analysis offers insights that are useful for the development of vaccine communication strategies more broadly, both in and beyond future pandemics, to ensure that public concerns are addressed, and misinformation and disinformation are appropriately countered.
Occupational physical activity and cardiovascular disease mortality in the United States, 1988–2019
Authors: Xia Tong , Chen Liwei , Li Jian
Published: January 2025

Background

Although leisure time physical activity (LTPA) is a beneficial factor for cardiovascular disease (CVD) mortality, relationships between occupational physical activity (OPA) and CVD mortality are inconclusive. We aimed to examine prospective associations of OPA with CVD mortality using a large representative sample of adult workers in the United States (US), and explore how socioeconomic status (SES) may influence these associations.

Methods

This cohort study included US workers (≥ 18 years) participating in the 1988 National Health Interview Survey (NHIS) and passively followed until December 31, 2019. Time (minutes/week) on strenuous OPA (e.g., lifting, pushing, or pulling heavy objects) was assessed at baseline by a questionnaire and categorized into 4 groups [i.e., none, low, medium, and high]. CVD mortality was identified by International Classification of Diseases, Tenth Version (ICD–10) and collected by the National Death Index database. We examined the association of OPA with CVD mortality using multivariable Cox proportional hazard regressions, controlling for age, sex, race/ethnicity, marital status, education, annual household income, occupation type, and pre-existing cardiometabolic disorders.

Results

In 28,604 participants (46.2% women; mean age 37.86 years), adjusted hazard ratios (95% CIs) of none, low, medium, and high OPA groups were 1.39 (1.01–1.91), 1.00 (reference), 1.18 (0.83–1.66) and 1.58 (1.12–2.22) for CVD mortality. The associations were stronger in workers with low education level (i.e., high school or less) [estimates of none, low, medium, and high OPA groups were 1.74 (1.09–2.78, P = 0.02), 1.00, 1.49 (0.92–2.42), and 1.87 (1.16–3.00)] or annual household income <$30,000 [estimates of OPA groups were 1.73 (1.16–2.56), 1.00, 1.29 (0.83–2.01), and 1.73 (1.14–2.65)].

Conclusions

We observed that workers with either high or no strenuous OPA had higher CVD mortality compared to those with low strenuous OPA, demonstrating a U-shaped association in the US. This association was particularly pronounced among workers with lower SES.
Progression and mortality of patients with cystic fibrosis in China
Authors: Zhou Wangji , Wang Yaqi , Yang Yanli , Sun Yanyan , Cheng Chongsheng , Dai Jinrong , Meng Shuzhen , Chen Keqi , Zhao Yang , Liu Xueqi , Zhang Dingding , Liu Song , Zhu Weiguo , Liu Yaping , Xu Kai-Feng , Tian Xinlun
Published: January 2025

Background

Patients with cystic fibrosis (CF) are rare in China and differ significantly from the Caucasian populations in terms of clinical and genetic characteristics. However, the progression and mortality of Chinese patients with CF have not been well described.

Results

This study included all 67 patients from the Peking Union Medical College Hospital CF cohort, with a median followed up time of 5.2 years. Compared to patients diagnosed with CF in childhood, adult-diagnosed patients exhibit a lower proportion of pancreatic exocrine insufficiency (25.0% vs. 77.8%, P = 0.001) and a higher body mass index (19.6 vs. 17.7 kg/m2, P = 0.045). According to the mixed-effects model, for patients ≤ 30 years of age at diagnosis, FEV1% predicted decreased 1.17% per year. The generalized linear regression model showed that higher baseline FEV1% predicted and occurrence of pulmonary exacerbations were associated with the progression of patients with CF. The survival rates at 5 years and 10 years after the diagnosis were 96.7% and 80.6%, respectively. The log-rank test showed baseline FEV1% predicted < 50%, and high CF-ABLE and 3-year prognostic scores were associated with mortality in patients with CF in China.

Conclusions

We reported the progression and mortality of patients with CF in China, which was a rare and relatively unknown population in the past. Baseline FEV1% predicted is associated with progression and mortality. Pulmonary exacerbations can accelerate the decline in lung function. The CF-ABLE and 3-year prognostic scores are applicable for predicting poor prognosis in patients with CF in China.
Antibody-based delivery of interleukin-2 modulates the immunosuppressive tumor microenvironment and achieves cure in pancreatic ductal adenocarcinoma syngeneic mice
Authors: Carbone Carmine , De Luca Roberto , Puca Emanuele , Agostini Antonio , Caggiano Alessia , Priori Lorenzo , Esposito Annachiara , Ascrizzi Serena , Piro Geny , Salvatore Lisa , De Sanctis Francesco , Ugel Stefano , Corbo Vincenzo , Neri Dario , Tortora Giampaolo
Published: January 2025

Background

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly type of cancer, with an extremely low five-year overall survival rate. To date, current treatment options primarily involve various chemotherapies, which often prove ineffective and are associated with substantial toxicity. Furthermore, immunotherapies utilizing checkpoint inhibitors have shown limited efficacy in this context, highlighting an urgent need for novel therapeutic strategies. This study investigates the preclinical efficacy of an innovative targeted therapy based on antibody-cytokine fusion proteins, specifically interleukin-2 (IL-2), a pivotal driver of cell-mediated immunity, fused to L19 antibody, which selectively binds to extra domain B of fibronectin (EDB-FN1) expressed in the tumor microenvironment.

Methods

We tested the effectiveness of different immunocytokines through in vivo characterization in syngeneic C57BL/6J orthotopic mouse models of PDAC. Based on these results, we decided to focus on L19-IL2. To assess the efficacy of this immunocytokine we developed an ex-vivo immune-spheroid interaction platform derived from murine 3D pancreatic cultures, and telomerase reverse transcriptase (TERT) specific T-lymphocytes. Moreover, we evaluated the anti-cancer effect of L19-IL2 in combination with standard therapy in vivo experiments in PDAC mouse models. Tumor samples collected after the treatments were characterized for tumor infiltrating immune cell components by bulk RNA sequencing (RNA-seq) and spatial transcriptomics (Stereo-seq) analysis.

Results

The tumor-targeted L19-IL2 fusion protein demonstrated potent, dose-dependent anti-tumor activity in mice with pancreatic tumors resistant to standard chemotherapy. Spatial Transcriptomics (ST) and RNA-seq analyses indicated that L19-IL2 treatment induced a significant influx of immune cells into the tumor microenvironment, with these cells expressing activation markers like granzymes, perforins, and the IL-2 receptors.

Conclusions

Our results demonstrated that L19-IL2 enhances immune infiltration and cytotoxicity, remodeling the “cold” tumor microenvironment (TME) in PDAC. This innovative antibody-cytokine fusion protein improves therapeutic outcomes, paving the way for novel targeted treatment strategies in PDAC.
Immunoglobulin replacement therapy in patients with primary and secondary immunodeficiencies: impact of infusion method on immunoglobulin-specific perceptions of quality of life and treatment satisfaction
Authors: Mallick Rajiv , Hahn Noemi , Scalchunes Christopher
Published: January 2025

Background

Immunoglobulin replacement therapy (IgRT) is the current standard of care for primary antibody deficiency patients (majority of all primary immunodeficiency (PID) diseases), with growing real-world evidence supporting use for secondary immunodeficiency (SID) patients. Infusion methods and practices can affect patients’ satisfaction with their treatment and perception of their health-related quality of life.

Methods

An online survey of US patients with PID and SID was conducted. This research investigates primarily the impact of two IgRT infusion methods, intravenous immunoglobulin therapy (IVIG) and subcutaneous immunoglobulin (SCIG), on the patient reported outcome (PRO) Life Quality Index (LQI) tool. Patient reported infusion time efficiency, physical and mental health (PROMIS GPH-2 and PROMIS GMH-2 respectively), patient acceptability of their symptom state (PASS), upper extremity disability (Quick DASH) and general health perception (via the GHP) are also investigated.

Results

Responses of 990 patients (391 IVIG and 598 SCIG) were analyzed. The median total LQI score amongst SCIG patients (84.7) was higher than IVIG patients (81.9) (p < 0.001), and was significantly higher on 3 out of 4 sub-domains of the LQI. SCIG patients scored higher on items that are related to convenience and reported less interference with everyday life: “Are convenient”, “Are scheduled according to my convenience”, “Do not interfere with my work/school” and “Require very little time and cost”. However, there was no significant difference between the two patient cohorts on other, non-IG specific PROs (PASS, PROMIS GPH-2 and GMH-2 and Quick DASH). Patient reported time per infusion was lower for SCIG infusions than IVIG infusions (pre-infusion time; 22 min vs. 63 min, p < 0.001, infusion time; 120 min vs. 240 min, p < 0.001, post-infusion time; 9 min vs. 31 min, p < 0.001). IVIG patients also reported more interference with everyday life than SCIG patients (82 vs. 86, p < 0.001).

Conclusions

The significantly higher LQI scores for patients receiving SCIG than those receiving IVIG confirms existing evidence that substitution of SCIG for IVIG may favorably impact immunoglobulin specific perceptions of quality of life and treatment satisfaction for appropriately selected patients. Our evidence on infusion times indicates similar improvement may be possible on infusion time efficiency.
The technical expert/clinical user/patient panel (TECUPP): centering patient and family perspectives in patient-reported measure development
Authors: Marsolais Elizabeth , Anhang Price Rebecca , Berdahl Carl T. , Shenk Anton , Schulson Lucy , O’Hanlon Claire E.
Published: January 2025

Patient and caregiver perspectives are increasingly incorporated into health care research and policymaking, but their inclusion in the quality measure development process often is not robust. We describe a stakeholder panel model for incorporating patient/caregiver voices in the development of patient-reported measures, the Technical Expert/Clinical User/Patient Panel (TECUPP) model. This model is characterized by significant or equal representation of people with lived experience of the disease or condition (as patients or caregivers) to the clinicians and others with technical expertise who typically comprise technical expert panels. We report key design features of the TECUPP model and how we used this model to develop survey-based patient experience measures of timeliness of cancer diagnosis. We describe benefits and challenges of using the TECUPP model and considerations to guide others who might use it as part of developing patient-centered quality measures, based on our experience convening a TECUPP to inform development of a patient-reported measure on timeliness of cancer diagnosis. Benefits include creating space for significant contributions from patients/caregivers and development of a shared understanding of patient experiences and observability of measure domains between clinicians and patients/caregivers. Challenges include time management and managing conversations outside the project scope. Measure development efforts implementing this model should consider recruiting diverse individuals, scheduling short and frequent meetings, enabling participation from all TECUPP members, developing accessible pre-read materials, anchoring meetings with patient stories, and encouraging multiple communication modes. The TECUPP model promotes discussion and understanding by patients/caregivers and clinicians/measure experts helpful for development of survey-based patient-reported measures.
Evaluating the reliability of a microperimetry-based method for assessing visual function in the junctional zone of geographic atrophy lesions
Authors: Alibhai A. Yasin , Moult Eric M. , Jamil Muhammad Usman , Raza Khadija , Morales Marco U. , Ribeiro Ramiro , Baumal Caroline R. , Fujimoto James G. , Waheed Nadia K.
Published: January 2025

Purpose

To assess the repeatability of a microperimetry methodology for quantifying visual function changes in the junctional zone of eyes with geographic atrophy (GA) in the clinical trial context.

Methods

A post hoc analysis of the OAKS phase III trial was conducted, which enrolled patients with GA secondary to age-related macular degeneration. Microperimetry using a standard 10 − 2 fovea centered grid was performed at baseline and follow-up visits. GA regions were traced on fundus autofluorescence (FAF) images. Two graders independently registered baseline microperimetry images with baseline FAF images in a sampling of 30 eyes from the OAKS study. Agreement between the two graders’ assessments of mean sensitivity and the number of scotomatous points within a ± 250 𝜇m GA junctional zone was assessed.

Results

The intraclass correlation (ICC) and coefficient of repeatability (CoR) for the mean junctional zone sensitivity were 0.987 and 0.214 dB, respectively. The ICC and CoR for the total number of scotomatous points within the junctional zone were 0.991 and 1.42, respectively.

Conclusions

The repeatability of the methodology and its compatibility with standard MP acquisitions appear to make it well-suited for identifying and analyzing retinal sensitivity within high-risk areas of the retina.

We present a microperimetry-based methodology for assessing visual function changes in the junctional zone of geographic atrophy lesions using a standard 10 − 2 fovea centered grid in a clinical trial context. The approach’s repeatability and compatibility with standard microperimetry grids may make it useful for assessing the effects of GA therapeutics.
Application of Mendelian randomization analysis to explore causal associations of aspirin use with bone mineral density and risk of fracture
Authors: Liu Qi-Pei
Published: January 2025

Objective

Previous observational studies on the association between aspirin use, bone mineral density (BMD), and fracture risk have yielded controversial results. This study explored the causal relationship between aspirin use, BMD, and fracture risk using Mendelian randomization (MR).

Methods

Summary data for aspirin use and BMD of five different body parts (femoral neck, lumbar spine, forearm, heel, and ultra distal forearm) and fractures were obtained from the integrative epidemiology unit open genome-wide association studies database for bidirectional MR analysis. An appropriate model was chosen based on Cochran's Q test, with inverse variance-weighted as the primary method for MR analysis, supplemented by the weighted-median and MR-Egger methods. MR-Egger and MR-PRESSO were used to test for horizontal pleiotropy and exclude significant outliers that could bias the results. Various sensitivity analyses, including leave-one-out analysis, were conducted to ensure the robustness of the findings.

Results

Aspirin use significantly increased lumbar spine BMD (odds ratio [OR] = 4.660; 95% confidence interval [CI]: 1.365–15.906; P = 0.014). No significant causal association was found between aspirin use and fracture risk (beta = 59.951; 95% CI: -265.189–385.091; P = 0.718). No significant reverse causality was observed.

Conclusion

This study indicates that aspirin use does not significantly affect fracture risk but has a significant protective effect on lumbar spine BMD, revealing a potential benefit of aspirin against osteoporosis.
From gaming to reality: effectiveness of skills transfer from competitive sandbox gaming environment to near and far contexts
Authors: Zhong Yuchun , Fryer Luke Kutszik , Zheng Shiyue , Shum Alex , Chu Samuel Kai Wah
Published: January 2025

Esports or competitive video gaming has been increasingly utilized to enhance essential twenty-first century skills. However, there is limited evidence on the extent to which the skills acquired from a gaming environment can be transferred to other settings. This study employed an experimental design to investigate the effectiveness of a competitive sandbox game environment in enabling the transfer of the 4Cs skills to both near and far tasks, in contrast with a non-game environment. A cohort of 110 students from a university were randomly allocated to both conditions for the 4Cs skills training. The skills transferability was measured through self-reports, observations, and interviews. The findings indicated no significant differences in the transfer of creativity, critical thinking, and communication skills in near and far settings following both training environments. Interestingly, a competitive gaming environment significantly facilitated the transfer of collaboration skills to near tasks evidenced by performance-based assessments. Moreover, although the hypotheses 1c and 3c were not statistically supported, the small to medium effect size suggests that there were practical differences between the groups in self-reported collaboration skills in near and far tasks. Additionally, analysis of individual interviews with 41 participants indicated that the successful transference was attributed to an array of scaffolds (i.e., mentorship, collaborative problem-solving environment, autonomy, and guided checklists) while the failure to detect positive effects was explained by various constraints (i.e., unfamiliarity with game rules, limited time, lack of practice, and established cognitive patterns). These findings add new insights into the literature on game-based learning and transfer of learning and inform researchers to further investigate the longitudinal effect of skills transfer and retention in both academic and professional spheres.
Transcatheter closure of multiple ventricular septal ruptures after acute myocardial infarction: a case report highlighting the role of 3D transthoracic echocardiography
Authors: Ardini Tengku Winda , Sarastri Yuke , Purba Joy Wulansari , Taufik Yasdika Imam , Asriri Suci , Nasution Ali Nafiah
Published: January 2025

Background

Post-infarct ventricular septal rupture (PI-VSR) is a rare complication of acute myocardial infarction (AMI) but has very serious implications. Managing PI-VSR using transcatheter closure (TCC) presents varying challenges depending on the patient’s condition. The aim of this study is to present a highly challenging case of multiple VSRs as a complication of AMI.

Case presentation: A 59-year-old male was admitted with symptoms of shortness of breath, dyspnea on exertion, orthopnea, and swelling of the lower extremities. He had typical chest pain related to infarction 2 weeks before his admission. On electrocardiogram (ECG) examination, evidence of an old myocardial infarction in the infero-antero-lateral regions was seen. Echocardiography showed mild mitral and tricuspid regularities. The left ventricular (LV) systolic function was mildly compromised, with a global ejection fraction of 44%. There was also a left-to-right VSR shunt in the apical region of the LV. Multiple defects as outlined by 3D transthoracic echocardiography (TTE)—the largest measuring 17 mm. Given the high risks of open-heart surgery, a percutaneous closure of the VSR was carried out using a 21 mm atrial septal defect (ASD) occluder. The device was satisfactorily placed, and there was an improvement in the clinical condition of the patient. He was discharged after his 8-day stay in the hospital.

Conclusion

Our study emphasizes that echocardiography with 3D imaging provides a more detailed view of the size and shape of the rupture and serves as a valuable modality for guiding the percutaneous transcatheter VSR closure procedure.
Attitudes towards mental health professionals in social media: infodemiology study
Authors: Battle Harriet , Álvarez-Mon Miguel Ángel , Lara-Abelenda Francisco J. , Perez-Araluce Rafael , Pinto da Costa Mariana
Published: January 2025

Background

Negative perceptions of mental health professionals can deter individuals from seeking mental healthcare. Given the high burden of mental health globally, it is essential to understand attitudes towards mental health professionals. Social media platforms like Twitter/X provide valuable insights into the views of the general population.

Aims

This study aimed to use social media to investigate the (a) public perceptions (positive or negative) of mental health professionals, (b) changes in these perceptions over time and (c) engagement levels with tweets about mental health professionals over time.

Method

We collected all tweets posted in English between 2007 and 2023, containing key terms such as ‘mental health’, ‘psychology’, ‘psychologist’, ‘psychiatry’, ‘psychiatrist’, ‘neurology’ and ‘neurologist’. A total of 1500 tweets were manually classified into categories, which were used in conjunction with semi-supervised machine learning to categorise a large data-set.

Results

For most key terms, there was a higher frequency of positive perceptions compared with negative, with this trend improving over time. However, tweets containing ‘psychiatrist’ exhibited a higher proportion of negative perceptions (n = 4872, 39.52% negative v. n = 1972, 15.99% positive before 2020). After 2020, the gap narrowed, yet negative perceptions continued to dominate (n = 5505, 36.10% negative v. n = 3472, 22.77% positive).

Conclusions

Overall, positive perceptions of mental health and mental health professionals increased over time. However, ‘psychiatrist’ had a consistently higher proportion of negative perceptions. This study underscores the need to improve public perception of psychiatrists, and demonstrates the potential of using Twitter/X to better understand public attitudes and reduce stigma associated with accessing mental health services.
Intranasal Delivery of a Ghrelin Mimetic Engages the Brain Ghrelin Signaling System in Mice
Authors: Poelman Renée , Le May Marie V , Schéle Erik , Stoltenborg Iris , Dickson Suzanne L
Published: January 2025

Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor (GHSR), promotes food intake and other feeding behaviors, and stimulates growth hormone (GH) release from the pituitary. Growth hormone secretagogues (GHS), such as GHRP-6 and MK-0677, are synthetic GHSR ligands that activate orexigenic neuropeptide Y neurons that coexpress agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus when administered systemically. Systemic GHRP-6 also stimulates GH release in humans and rats. Thus, GHS and ghrelin have therapeutic relevance in patients who could benefit from its orexigenic and/or GH-releasing effects. This study examined whether intranasal delivery of ghrelin, GHRP-6, or MK-0677 engages the brain ghrelin signaling system.

Effective compounds and doses were selected based on increased food intake after intranasal application in mice. Only GHRP-6 (5 mg/kg) increased food intake without adverse effects, prompting detailed analysis of meal patterns, neuronal activation in the arcuate nucleus (via Fos mapping) and neurochemical identification of c-fos messenger RNA (mRNA)-expressing neurons using RNAscope. We also assessed the effect of intranasal GHRP-6 on serum GH levels.

Intranasal GHRP-6 increased food intake by increasing meal frequency and size. Fos expression in the arcuate nucleus was higher in GHRP-6–treated mice than in saline controls. When examining the neurochemical identity of c-fos-mRNA–expressing neurons, we found coexpression with 63.5 ± 1.9% Ghsr mRNA, 79 ± 6.8% Agrp mRNA, and 11.4 ± 2.5% Ghrh mRNA, demonstrating GHRP-6's ability to engage arcuate nucleus neurons involved in food intake and GH release. Additionally, intranasal GHRP-6 elevated GH serum levels. These findings suggest that intranasal GHRP-6, but not ghrelin or MK-0677, can engage the brain ghrelin signaling system.
Subjunctive: A Manifesto About Language, Territory, and the Yet to Come
Authors: Garza Cristina Rivera
Published: January 2025

Mexican-American author Cristina Rivera Garza gives us the language of the future in the subjunctive, which “lays the groundwork for the irruption. . . . The subjunctive is the smuggler who crosses the border of the future bearing unknown cargo.”
Medical Therapy Alone for Ommaya Reservoir–Associated Bacterial Meningitis: When It Works and When It Fails
Authors: Tuohy Kyle , Dowd Richard , Ali Ayesha , Badani Aarav , Sichinga Krishana , Zacharia Brad E. , Mansouri Alireza , Aregawi Dawit , Glantz Michael
Published: January 2025

BACKGROUND AND OBJECTIVES:

Administration of intraventricular chemotherapy through Ommaya reservoir is indicated for certain forms of leptomeningeal disease. However, ventricular reservoirs carry a substantial risk of infection. The conventional approach to managing reservoir-associated infections involves removal of the reservoir and systemic antibiotic therapy, but this strategy necessitates additional procedures to remove and subsequently replace the device. We evaluated the success rate of standardized, multimodal medical therapy alone in treating reservoir-associated meningitis and factors associated with the need for device removal.

METHODS:

We used the International Neoplastic Meningitis Academic Registry Consortium database to identify patients at our institution with reservoir-associated bacterial meningitis. A standardized antibiotic regimen of oral rifampin, intraventricular vancomycin, and another intravenous antibiotic based on the infecting organism was used to treat infections for 10 to 14 days. We evaluated the rate of infection clearance and factors associated with success of therapy without reservoir removal.

RESULTS:

Forty-eight infections in 33 patients (5.79% of all patients) were identified. Before infection, reservoirs were accessed a median of 6 (1-14) times. Infections were eradicated without reservoir removal in 39 of 48 patients (81.3%). Cerebrospinal fluid (CSF) leak/local wound infection was the only factor associated with the need for reservoir removal (odds ratio = 18.3 [3.68-141], P < .001) on multivariate analysis, and 98.0% of patients without this characteristic were cured with medical therapy alone. Other characteristics such as age, myelosuppression, tumor histology, number of reservoir accesses, concurrent systemic chemotherapy, or infecting organism were not predictive of reservoir removal. Random forest and gradient boost machine learning models further confirmed CSF leak/local wound infection to be the most important predictor of removal.

CONCLUSION:

Most patients who develop a reservoir-associated infection can be successfully treated with a standardized antibiotic regimen alone, without additional surgery for reservoir removal and subsequent replacement. However, CSF leak/reservoir site infection is strongly associated with failure of medical therapy and warrants early device removal.
Impact of Revascularization Timing on Clinical Outcomes of Symptomatic Moyamoya Disease: A Systematic Review and Multivariate Analysis
Authors: Edelbach Brandon , Lopez-Gonzalez Miguel Angel
Published: January 2025

BACKGROUND AND OBJECTIVES:

Despite a substantial body of literature describing the efficacy of revascularization compared with conventional management of moyamoya disease (MMD), the impact of the timing of revascularization relative to stroke onset remains inadequately characterized. The aim of this review was to synthesize existing research to guide clinicians in the optimal timing of revascularization in symptomatic MMD.

METHODS:

A comprehensive literature review was performed to identify studies reporting on timing of revascularization. Studies were divided into revascularization within 3 months of stroke, between 3 and 6 months of stroke, or >6 months from stroke event.

RESULTS:

A total of 3049 cases and 3151 treated cerebral hemispheres were included. There were 91 individuals (2.98%) in the 3 months to intervention cohort, 152 (4.92%) individuals in the 3 to 6 months to the intervention cohort, and 2806 (92.0%) individuals in the >6 months to the intervention cohort. The average follow-up time was 43.8 ± 35.19 months. Clinical improvement was reported in 83.4% of cases overall. The 3-to-6-month poststroke preoperative interval has the highest frequency of clinical improvement (90.2%), followed by the >6-month preoperative interval (83.4%). The preoperative interval of <3 months had the lowest frequency of clinical improvement (76.5%). Comparison of average treatment effect in the treated demonstrated reduced frequency of improved clinical outcome (Mean difference: −22.6, SE: 9.15, P = .013) and increased frequency of worse clinical outcome (Mean difference: 20.1, SE: 7.38, P = .006) in the <3 months cohort. The >6 months cohort was found to be associated with a reduced frequency of worse clinical outcome (Mean difference −1.81, SE: 0.349, P = .001).

CONCLUSION:

The findings of this meta-analysis suggest that, in cases where it is clinically feasible to delay revascularization following an acute neurological event in patients with MMD, postponing intervention is warranted.
FGFR2 directs inhibition of WNT signaling to regulate anterior fontanelle closure during skull development
Authors: Bobzin Lauren , Nickle Audrey , Ko Sebastian , Ince Michaela , Huang Aaron , Bhojwani Arshia , Roberts Ryan , Merrill Amy E.
Published: January 2025

The calvarial bones of the infant skull are linked by transient fibrous joints known as sutures and fontanelles, which are essential for skull compression during birth and expansion during postnatal brain growth. Genetic conditions caused by pathogenic variants in FGFR2, such as Apert, Pfeiffer, and Crouzon syndromes, result in calvarial deformities due to premature suture fusion and a persistently open anterior fontanelle (AF). In this study, we investigated how Fgfr2 regulates AF closure by leveraging mouse genetics and single-cell transcriptomics. We find that AF cells, marked by the tendon/ligament factor SCX, are spatially organized into ecto- and endocranial domains that selectively differentiate into ligament, bone, and cartilage to form the posterior frontal suture. We show that AF cell differentiation is non-autonomously regulated by FGFR2 signaling in osteogenic front cells of the frontal bones, which regulate WNT signaling in neighboring AF cells by expressing the secreted WNT inhibitor Wif1. Upon loss of Fgfr2, Wif1 expression is downregulated, and AF cells fail to form the posterior frontal suture. This study identifies an FGF-WNT signaling circuit that that directs suture formation within the AF during postnatal development.
Perceptions of communicable disease surveillance system attributes among key informants at primary healthcare centers in Jeddah, Saudi Arabia
Authors: Alshehri Mohammed H , Alzahrani Khalid M , Alshehri Ahlam D , Alghamdi Nawaf M , MohammedHussain Abdullah M
Published: January 2025

Background Communicable disease surveillance systems (CDSSs) are essential for the timely identification and response to health threats, particularly in cities such as Jeddah, which serve as major gateways for international travelers and pilgrims. This study examined key informants’ perceptions of CDSS attributes at primary healthcare centers (PHCCs) in Jeddah, Saudi Arabia. Methods A cross-sectional study was conducted from November 2017 to March 2018 at 45 PHCCs. Key informants completed a validated electronic questionnaire using a seven-point Likert scale to evaluate their perceptions of CDSS attributes, including timeliness, usefulness, simplicity, acceptability, and flexibility. A sensitivity analysis was performed to assess the effect of neutral responses on the findings. Results Of the 42 eligible key informants, 40 participated, yielding a 95% response rate. The CDSS was perceived as timely by 69% of participants, whereas lower proportions rated it as useful (42%), simple (36%), acceptable (24%), and flexible (27%). No substantial associations were found between perceptions and variables such as years of experience, family medicine specialization, or CDSS training. Key informants highlighted staffing gaps (85%) and the need for electronic system implementation (95%) as primary areas for improvement. Conclusion While the CDSS demonstrated relative strength in timeliness, substantial improvements are required in other attributes. The findings underscore the importance of enhanced electronic systems, adequate staffing, and effective training programs. Further quantitative assessments are needed to validate these perceptions and inform improvements at local and national levels.
O polskie duchowieństwo w Gdańsku. Uwagi na marginesie petycji z 3 czerwca 1945 r. w sprawie przywrócenia parafii pw. św. Stanisława BM we Wrzeszczu i ustanowienia polskiego przedstawiciela w kurii biskupiej
Authors: Gucewicz Daniel
Published: January 2025

Po zdobyciu Gdańska przez Armię Czerwoną w marcu 1945 r. rozpoczął się napływ polskich osadników, należących w swej masie do Kościoła rzymskokatolickiego i w nowym miejscu poszukujących kościołów, w których mogliby realizować swoje potrzeby duchowe. W wielu parafiach spotykali jednak lokalnych księży diecezji gdańskiej, pochodzenia niemieckiego bądź pomorskiego, którzy choć w większości znali język polski, to przybyszom częściej kojarzyli się ze znienawidzonymi okupantami. Z kolei napływający do Gdańska polscy księża natrafiali na opór biskupa gdańskiego Carla Marii Spletta, który z początku nie włączał ich w struktury diecezjalne (choć nie był przeciwny ich osiedlaniu się i podejmowaniu pracy duszpasterskiej). Pretekstem do podjęcia rozważań na temat sytuacji duszpasterskiej w Gdańsku w połowie 1945 r. jest edytowana w aneksie petycja z czerwca 1945 r. polskich wiernych z Wrzeszcza, domagających się interwencji polskich władz w działalność biskupa: przywrócenia polskiej parafii przy nieczynnym kościele św. Stanisława BM (zamienionym przez Niemców w 1939 r. w garaż) i ustanowienia polskiego przedstawiciela w kurii biskupiej. Wiele wskazuje na to, że inicjatywa nie była oddolna, lecz zainicjowana przez czynniki polityczne (PPS) w ramach działań władz miasta zmierzających do jego jak najszybszej polonizacji, z czym łączyło się usunięcie wszystkich Niemców, w tym osób duchownych. Treść dokumentu współgrała przy tym z kampanią prasową atakującą Kościół katolicki za pomocą antyniemieckich resentymentów, która przygotowała grunt polityczny pod aresztowanie bp. Spletta, a następnie zerwanie konkordatu.
Oral and intestinal manifestations of giant cell arteritis
Authors: Pernet Mathieu , Moi Laura , Serra Fulvia , Garin Nicolas
Published: January 2025

Background: Giant cell arteritis (GCA) is the most common primary vasculitis in individuals over 50 years of age. GCA typically affects large- and medium-sized arteries and is classically associated with cranial manifestations of ischaemia, such as headaches (notably in the temporal region), jaw claudication and visual symptoms that can lead to blindness. Extracranial symptoms are less frequently reported and are related to involvement of the thoracic and abdominal aorta and its main branches. Classic diagnostic tools (such as temporal artery ultrasonography and temporal artery biopsy) can be negative in extracranial GCA. Case description: We report a difficult diagnosis of GCA in a 75-year-old woman who developed painful tongue ulcers that responded to prednisone treatment. However, a comprehensive diagnostic work-up did not lead to a certain diagnosis of GCA and corticosteroids were stopped after one month. A few months later, the patient suffered from mechanical ileus secondary to ischaemic stenosis of the small bowel. Pathological examination of the small bowel resection, and a second FDG-PET/CT, led to the diagnosis of extracranial GCA. Conclusions: We present a case of CGA which sequentially affected cranial and extracranial arteries and illustrate pitfalls in the diagnosis of this polymorph condition.
A Contribuição da Territorialização na Atenção Básica na Formação Médica: Um Relato de Experiência
Authors: Carlos Júnior Toebe Silva  , Gabriela Tatibana Fukuya  , Paulo Gabriel da Silva Mota  , Roger dos Santos Felix  , Prado Bárbara Grassi
Published: January 2025

Trata- se de um relato de experiência de acadêmicos de Medicina da Universidade Federal de Rondonópolis, atuando em uma Unidade de Saúde da Família em Rondonópolis, Brasil, em 2021. Objetivando-se compreender o processo de territorialização e a sua contribuição no desenvolvimento do processo educativo de alunos de Medicina, durante suas práticas na Atenção Primária, os autores colheram as informações do território de abrangência da unidade por meio de busca ativa. Ao longo as atividades realizadas, os alunos obtiveram um íntimo contato com o processo de territorialização e suas etapas, além de perceberem a necessidade de esse processo ser uma ação contínua e multidisciplinar. Porém, apesar das ações desenvolvidas, identificaram-se dificuldades, principalmente relacionadas à falta de Agentes Comunitários de Saúde na unidade onde atuaram. A despeito disso, a experiência desses discentes com a territorialização da Atenção Básica permitiu-lhes entender a relevância de tal processo, aproximando-os dos usuários e do serviço de saúde e fortalecendo a integração ensino-serviço-comunidade, o que implicou positivamente em suas formações.
Ascensão E Queda Da Unasul: Ideologia, Política Externa E Integração Regional A Partir Dos Casos Da Argentina E Brasil | Rise And Fall Of Unasur: Ideology, Foreign Policy And Regional Integration Based On The Cases Of Argentina And Brazil
Authors: Corrêa Tammy Eduarda
Published: January 2025

RESUMO
Este artigo tem como objetivo analisar e identificar sob uma perspectiva histórico-comparada o que explica a ascensão e declínio da Unasul. O estudo examina o período de 2008 a 2022 e caracteriza-o através das particularidades políticas e ideológicas na América do Sul, especialmente no que tange à consonância de políticas externas, abrangidas pela alternância dos fenômenos da onda rosa e da onda conservadora. A principal hipótese é que a convergência e a divergência ideológica influenciam o contexto sul-americano nas tendências e nos tipos de cooperação regional. Duas nações determinantes para a análise são a Argentina e o Brasil que, através das transições de governo e ideologias no poder, influenciam em mudanças quanto ao tipo de interação e integração regional através de suas políticas externas. Em consequência, é percebido um processo de esvaziamento da Unasul sob críticas de viés político-ideológico.
Palavras-chave: Unasul; Política Externa; Ideologia.
 
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ABSTRACT
This article aims to analyze and identify, through a historical-comparative perspective, what explains the rise and decline of Unasur. The study examines the period from 2008 to 2022 and characterizes it through the political and ideological particularities of South America, especially regarding the consonance of foreign policies, encompassed by the alternation of the pink tide and conservative wave phenomena. The main hypothesis is that ideological convergence and divergence influence the South American context in terms of trends and types of regional cooperation. Two decisive nations for the analysis are Argentina and Brazil, which, through government transitions and ideologies in power, influence changes in the type of interaction and regional integration through their foreign policies. As a result, a process of emptying of Unasur is perceived under criticism of political-ideological bias.
Keywords: Unasur; Foreign Policy; Ideology.