bluuebunny/crossref_metadata_2025 huggingface dataset:
Convexity subarachnoid hemorrhage revealed contralateral internal carotid artery dissection due to Eagle syndrome: a case report
Authors: Obara Kazuki , Furuta Takahiro , Yagi Chikako , Nakai Noriyoshi , Suzuki Junichiro , Katsuno Masahisa , Ito Yasuhiro
Published: October 2024

Background

Atraumatic localized convexity subarachnoid hemorrhage (cSAH) is an uncommon form of nonaneurysmal subarachnoid hemorrhage characterized by bleeding limited to the cerebral convexities. Ipsilateral cSAH can result from a variety of causes, such as internal carotid artery stenosis, obstruction, and dissection, although concomitant contralateral cSAH is exceptionally rare. In this case, the initial findings of cSAH led us to discovering contralateral internal carotid artery dissection (ICAD) and an elongated styloid process (ESP). ESP is recognized as a risk factor for ICAD, which is a hallmark of Eagle syndrome. This sequence of findings led to the diagnosis of Eagle syndrome, illustrating a complex and intriguing interplay between cerebrovascular conditions and anatomical variations.

Case presentation

A 47-year-old Japanese woman experienced acute onset of headache radiating to her neck, reaching its zenith approximately two hours after onset. Given the intractable nature of the headache and its persistence for three days, she presented to the emergency department. Neurological examination revealed no abnormalities, and the coagulation screening parameters were within normal ranges. Brain computed tomography (CT) revealed right parietal cSAH, while CT angiography (CTA) revealed ICAD and an ESP measuring 30.1 mm on the left side, positioned only 1.4 mm from the dissected artery. The unusual occurrence of contralateral cSAH prompted extensive and repeated imaging reviews that excluded reversible cerebral vasoconstriction syndrome (RCVS), leading to a diagnosis of left ICAD secondary to Eagle syndrome. The patient underwent conservative management, and the dissected ICA spontaneously resolved. The patient has remained recurrence-free for two and a half years.

Conclusions

Managing cSAH requires diligent investigation for ICAD, extending beyond its identification to explore underlying causes. Recognizing Eagle syndrome, though rare, as a potential etiology of ICAD necessitates the importance of evaluating ESPs. The method for preventing recurrent cervical artery dissection due to Eagle syndrome is controversial; however, conservative management is a viable option.
Kawasaki disease before and during the COVID-19 pandemic: a single-center comparative study in Switzerland
Authors: Epitaux Justine , Sekarski Nicole , Bressieux-Degueldre Sabrina
Published: October 2024

Background

Kawasaki disease is a rare systemic inflammatory syndrome that mainly affects children under five years of age and is the first cause of pediatric acquired cardiovascular disease. The pathogenesis is complex and a viral trigger is suspected, as well as genetic susceptibility. Multiple studies around the world have shown a decrease in the incidence of Kawasaki disease and have hypothesized that the different sanitary measures enforced in each country during the pandemic period could be responsible to a certain extent. The aim of this study is to evaluate the effects of the COVID-19 pandemic on the disease’s incidence, defining characteristics, coronary artery outcomes and management in a tertiary center in Switzerland.

Methods

This study is a retrospective analysis of children who have been diagnosed with Kawasaki disease that compares clinical, laboratory, SARS-CoV-2 exposure, and echocardiographic data as well as treatments before (January 1st 2017 to February 24th 2020) and during (February 25th 2020 to December 31st 2022) the COVID-19 pandemic in Switzerland. Statistical significance of differences in the compared parameters was assessed.

Results

Of the 90 patients included, 31 belonged to the first group and 59 belonged to the second group. There was a statistically significant (p < 0.05) increase in incidence during the pandemic period (5.91/100,000 children) of 88% compared to the pre-pandemic period (3.14/100,000 children). A lesser seasonal variation was observed during the pandemic. 30% of the patients in the pandemic group had an exposure to SARS-CoV-2. There was no other notable difference in demographic factors, clinical presentation, coronary outcome or administered treatment.

Conclusions

To the best of our knowledge, this is the first prolonged European study comparing Kawasaki disease before and during the COVID-19 pandemic. There was a significant increase in incidence in Kawasaki disease during the COVID-19 pandemic. In contrast, studies done in Japan, South Korea and the USA have shown a decrease in incidence. Differences in methodologies, genetics, ethnicities, environments, microbiome-altering behaviors, sanitary measures and SARS-CoV-2 spread are factors that should be considered. Further studies analyzing the differences between countries with increased incidence of Kawasaki disease could help better understand the relevance of such factors and provide more insight into the etiologies of this particular disease.
The intention of Egyptian healthcare workers to take the monkeypox vaccine: is urgent action required?
Authors: Ghazy Ramy Mohamed , Hussein Mai , Abdu Shymaa Mamdouh Mohamed , El-sayed Ellakwa Doha , Tolba Mahmoud M. , Youssef Naglaa , Mahboob Amira Saad , Abd ElHafeez Samar
Published: October 2024

Background

In light of the ongoing monkeypox (MPOX) epidemic, healthcare workers (HCWs) have been in contact with various diseases. Therefore, they should take appropriate preventive and control measures to maintain their health. This study assessed Egyptian HCWs’ intentions to take MPOX vaccines.

Methods

A cross-sectional survey was conducted using social media platforms between September 27 and November 4, 2022. An anonymous online survey using the 5C scale was conducted using convenience and snowball sampling methods to assess the five psychological antecedents of vaccination (i.e., confidence, constraints, complacency, calculation, and collective responsibility).

Results

A total of 399 HCWs with a mean age of 32.6 ± 5.7 participated in this study. Of them, 89.7% were female. The five C psychological antecedents of vaccination were as follows: 55.9% were confident about vaccination, 50.6% were complacent, 56.6% experienced constraints, 60.7% calculated the risk and benefit, and 58.4% had collective responsibility. Multivariate analysis showed that high income level and having information about MPOX were significant predictors of confidence in the MPOX vaccines (adjusted odds ratio ((AOR) = 4.19, 95% CI (1.12– 15.59), P = 0.032). Participants aged 31–45 years and 19–30 years showed significant association (AOR = 2.46, 95% CI (0.85–7.15), P = 0.096) and (AOR = 4.19, 95% CI (1.39–12.64), P = 0.011), respectively. Having an idea about the MPOX vaccines significantly predicted the complacency domain (AOR = 3.77, 95%CI (1.47–9.65, P = 0.006). Moreover, precollege/undergraduate education and having an idea about MPOX vaccination were significant predictors of the constraint domain (AOR = 1.81.95% CI (1.09–2.99, P = 0.020), (AOR = 2.70, 95% CI (1.05–6.95, P = 0.038), respectively). Female sex, having a diploma, postgraduate studies, and having an idea about MPOX vaccine significantly predicted calculation domain (AOR = 2.06, 95% CI (1.05–4.04, P = 0.035), (AOR = 3.98,95% CI (1.33–11.87, P = 0.013), (AOR = 2.02, 95% CI (1.25–3.26, P = 0.004) & (AOR = 2.75. 95% CI (1.05–7.18, P = 0.039), respectively. The only significant predictor of collective responsibility was having a diploma and postgraduate studies (AOR = 3.44, 95% CI (1.21–9.78, P = 0.020), (AOR = 1.90,95% CI (1.17–3.09, P = 0.009).

Conclusions

Efforts to control MPOX should focus on promoting protective measures such as the vaccination of HCWs as well as raising their awareness about the updated information regarding the virus and the approved vaccines.
Sex-specific differences of cardiopulmonary fitness and pulmonary function in exercise-based rehabilitation of patients with long-term post-COVID-19 syndrome
Authors: Garbsch René , Schäfer Hendrik , Kotewitsch Mona , Mooren Johanna M. , Waranski Melina , Teschler Marc , Vereckei Katalin , Böll Gereon , Mooren Frank C. , Schmitz Boris
Published: October 2024

Background

Post-COVID-19 Syndrome (PCS) entails a spectrum of symptoms, including fatigue, reduced physical performance, dyspnea, cognitive impairment, and psychological distress. Given the effectiveness of exercise-based rehabilitation for PCS, this study examined the efficacy of rehabilitation for PCS patients, focusing on sex-specific differences.

Methods

Prospective cohort study during inpatient rehabilitation. Cardiopulmonary exercise testing and spirometry were performed at admission and discharge. Questionnaires were used to assess fatigue, health-related quality of life, wellbeing, and workability for up to 6 months.

Results

145 patients (36% female, 47.1 ± 12.7 years; 64% male, 52.0 ± 9.1 years; p = 0.018) were referred to rehabilitation 262.0 ± 128.8 days after infection (female, 285.5 ± 140.6 days; male, 248.8 ± 112.0 days; p = 0.110). Lead symptoms included fatigue/exercise intolerance (81.4%), shortness of breath (74.5%), and cognitive dysfunction (52.4%). Women presented with higher relative baseline exercise capacity (82.0 ± 14.3%) than males (68.8 ± 13.3%, p < 0.001), but showed greater improvement in submaximal workload (p = 0.026). Men exhibited higher values for FEV1, FEV1/VC, PEF, and MEF and lower VC at baseline (p ≤ 0.038), while FEV1/VC improvement more in women (p = 0.027). Higher baseline fatigue and lower wellbeing was detected in women and correlated with impaired pulmonary function (p < 0.05). Disease perception including fatigue, health-related quality of life, wellbeing and workability improved with rehabilitation for up to six-month.

Conclusions

Rehabilitation improves cardiopulmonary fitness, pulmonary function and disease burden in women and men with long-term PCS. Women with PCS may benefit from intensified respiratory muscle training. Clinical assessment should include cardiopulmonary exercise testing and pulmonary function tests and fatigue assessments for all PCS patients to document limitations and tailor therapeutical strategies.
Differences between women and men in prolonged weaning
Authors: Röser Evelyn , Michels-Zetsche Julia D. , Ersöz Hilal , Neetz Benjamin , Höger Philipp , Trinkmann Frederik , Müller Michael M. , Klotz Laura , Kontogianni Konstantina , Winter Hauke , Dahlhoff Jana Christina , Krysa Sabine , Herth Felix J. F. , Trudzinski Franziska C.
Published: October 2024

Background

In recent years, the importance of sex as a factor influencing medical care has received increasing attention in the field of intensive care medicine. The objective of this study was to examine the influence of sex in prolonged weaning.

Methods

A retrospective analysis of patients undergoing prolonged weaning at Thoraxklinik, University Hospital Heidelberg between 12/08 and 12/23 was conducted. Patients with neuromuscular diseases were excluded from the analyses. The risk factors for weaning failure in men and women were identified through stepwise cox-regression analyses.

Results

A total of 785 patients were included, of whom 313 (39.9%) were women. 77.9% of the women and 75.4% of the men were successfully weaned from invasive ventilation. In group comparisons and multivariable analyses, sex was not found to be a risk factor for weaning failure. Cox regression analyses were performed separately for both sexes on the outcome of weaning failure, adjusting for relevant covariates. The results indicated that age ≥ 65 years (HR 2.38, p < 0.001) and the duration of IMV before transfer to the weaning centre (HR 1.01/day, p < 0.001) were independent risk factors in men. In women, however, the duration of IMV before transfer (HR 1.01, p < 0.001), previous non-invasive ventilation (HR 2.9, p 0.005), the presence of critical illness polyneuropathy (HR 1.82; p = 0.040) and delirium (HR 2.50, p = 0.017) were identified as relevant risk factors. In contrast delirium was associated with a favourable weaning outcome in men (HR 0.38, p = 0.020) and nosocomial pneumonia as a reason for prolonged weaning in women (HR 0.43; p = 0.032).

Conclusion

The analyses indicate that there are sex-based differences in the risk factors associated with weaning failure. Further studies, ideally prospective, should confirm these findings to assess whether sex is a factor that should be taken into account to improve weaning outcomes.
Elucidating the power of arginine restriction: taming type I interferon response in breast cancer via selective autophagy
Authors: Lamsal Apsana , Andersen Sonja Benedikte , Johansson Ida , Desgarnier Marie-Catherine Drigeard , Wolowczyk Camilla , Engedal Nikolai , Vietri Marina , Bjørkøy Geir , Giambelluca Miriam S. , Pettersen Kristine
Published: October 2024

Background

Type I interferons (IFN-I) are potent alarm factors that initiate cancer cell elimination within tumors by the immune system. This critical immune response is often suppressed in aggressive tumors, thereby facilitating cancer immune escape and unfavorable patient outcome. The mechanisms underpinning IFN-I suppression in tumors are incompletely understood. Arginase-1 (ARG1)-expressing immune cells that infiltrate tumors can restrict arginine availability by ARG1-mediated arginine degradation. We hypothesized that arginine restriction suppresses the IFN-I response in tumors.

Methods

Comprehensive, unbiased open approach omics analyses, various in vitro techniques, including microscopy, qPCR, immunoblotting, knock-down experiments, and flow cytometry were employed, as well as ex vivo analysis of tumor tissue from mice. Several functional bioassays were utilized to assess metabolic functions and autophagy activity in cancer cells.

Results

Arginine restriction potently induced expression of selective autophagy receptors, enhanced bulk and selective autophagy and strongly suppressed the IFN-I response in cancer cells in an autophagy-dependent manner.

Conclusion

Our study proposes a mechanism for how tumor-infiltrating immune cells can promote cancer immune escape by dampening the IFN-I response. We suggest ARG1 and autophagy as putative therapeutic targets to activate the IFN-I response in tumors.
Monocyte subsets in breast cancer patients under treatment with aromatase inhibitor and mucin-1 cancer vaccine
Authors: Knöbl Viktoria , Maier Lukas , Grasl Stefan , Kratzer Carmen , Winkler Felix , Eder Vanessa , Hayden Hubert , Sahagun Cortez Maria Amparo , Sachet Monika , Oehler Rudolf , Frantal Sophie , Fesl Christian , Zehetner Karin , Pfeiler Georg , Bartsch Rupert , Fitzal Florian , Singer Christian F. , Filipits Martin , Gnant Michael , Brostjan Christine
Published: October 2024

Background

Monocytes comprise subsets of classical, intermediate and non-classical monocytes with distinct anti- or pro-tumor effects in breast cancer (BC). They are modulated by estrogen, and can contribute to BC control by endocrine therapy in preclinical models.

Methods

To elucidate whether changes in monocyte subsets are associated with treatment and response, we investigated peripheral blood samples of 73 postmenopausal women with estrogen receptor (ER) positive BC, who received aromatase inhibitor therapy with or without the mucin-1 vaccine tecemotide in the ABCSG34 trial. Blood was retrieved at baseline, midterm and end of therapy, and was analyzed for the distribution and ER expression of monocyte subsets by flow cytometry.

Results

When 40 healthy, age-matched women were compared with BC patients before treatment start, ER levels of monocytes did not differ, yet patients presented with a higher frequency of classical and fewer non-classical monocytes. Endocrine therapy triggered a significant increase in ER levels in all monocyte subsets, without affecting subset distribution. Vaccination had no overall impact on subset frequency and ER expression. Yet, a shift from intermediate to classical monocytes during therapy correlated with changes in plasma cytokines and chemokines and was significantly associated with low residual cancer burden in vaccinated patients. Without tecemotide, baseline ER levels in classical monocytes were significantly higher in women with good response to endocrine therapy.

Conclusions

This study identified classical monocytes to be associated with ER positive BC and with patient response to neoadjuvant endocrine treatment and cancer vaccination.
“I managed to stand on my own. I saved my baby’s life.”: qualitative analysis of birth experiences from women living with HIV in Cape Town, South Africa
Authors: Weber Alison Z. , Jensen Destry , DiClemente-Bosco Kira , Tsawe Nokwazi , Knight Lucia , Myer Landon , Pellowski Jennifer A.
Published: October 2024

Background

There is growing recognition of obstetric violence in health facilities across the globe. With nearly one in three pregnant women living with HIV in South Africa, it is important to consider the influence of HIV status on birth experiences, including potential experience of obstetric violence as defined by the Respectful Maternity Care Charter. This qualitative analysis aims to understand the factors that shape birth experiences of women living with HIV, including experiences at the nexus of HIV status and obstetric violence, and how women react to these factors.

Methods

Data were collected in a Midwife Obstetric Unit in Gugulethu, Cape Town, South Africa, through 26 in-depth interviews with women living with HIV at 6–8 weeks postpartum. Interviews included questions about labor and early motherhood, ART adherence, and social contexts. We combined template style thematic analysis and matrix analysis to refine themes and subthemes.

Results

Participants described a range of social and structural factors they felt influenced their birth experiences, including lack of resources and institutional policies. While some participants described positive interactions with healthcare providers, several described instances of obstetric violence, including being ignored and denied care. Nearly all participants, even those who described instances of obstetric violence, described themselves as strong and independent during their birth experiences. Participants reacted to birth experiences by shifting their family planning intentions, forming attitudes toward the health facility, and taking responsibility for their own and their babies’ safety during birth.

Conclusions

Narratives of negative birth experiences among some women living with HIV reveal a constellation of factors that produce obstetric violence, reflective of social hierarchies and networks of power relations. Participant accounts indicate the need for future research explicitly examining how structural vulnerability shapes birth experiences for women living with HIV in South Africa. These birth stories should also guide future intervention and advocacy work, sparking initiatives to advance compassionate maternity care across health facilities in South Africa, with relevance for other comparable settings.
Clinical symptoms, comorbidities and health outcomes among outpatients infected with the common cold coronaviruses versus influenza virus
Authors: Iyadorai Thevambiga , Lim Sin How , Wong Pui Li , Sii Hoe Leong , P’ng Chun Keat , Ee Soon Sean , Tan Maw Pin , Hanafi Nik Sherina , Ng Kim Tien , Chook Jack Bee , Takebe Yutaka , Chan Kok-Gan , Singh Sarbhan , Sam I-Ching , Tee Kok Keng
Published: October 2024

Background

Common cold coronaviruses (ccCoVs) and influenza virus are common infectious agents causing upper respiratory tract infections (RTIs). However, clinical symptoms, comorbidities, and health effects of ccCoV infection remain understudied.

Methods

A retrospective study evaluated 3,935 outpatients with acute upper RTI at a tertiary teaching hospital. The presence of ccCoV and influenza virus was determined by multiplex molecular assay. The demographic, clinical symptoms, and health outcomes were compared between patients with ccCoV (n = 205) and influenza (n = 417) infections. Multivariable logistic regression was employed to evaluate predictors and health outcomes over a one-year follow-up.

Results

Sore throat, nasal discharge, headache, and myalgia were more predominant in ccCoV infection; fever was common in influenza. Most patients reported moderate symptoms severity (49.8% ccCoV, 56.1% influenza). Subsequent primary care visits with symptoms of RTI within a year were comparable for both infections (27.3% ccCoV vs. 27.6% influenza). However, patients with influenza reported increased primary care visits for non-RTI episodes and all-cause hospital admission. Baseline comorbidities were associated with increased primary care visits with symptoms of RTI in either ccCoV (adjusted odds ratio [aOR] 2.5; 95% confidence interval [CI] 1.1–5.9; P = 0.034) or influenza (OR 1.9; 95% CI 1.1–3.1; P = 0.017) infections, due probably to the dysregulation of the host immune response following acute infections. In patients infected with influenza infection, dyslipidemia was a predictor for subsequent primary care visits with symptoms of RTI (unadjusted OR 1.8; 95% CI 1.0–3.0; P = 0.040).

Conclusions

Both influenza and ccCoV infection pose significant disease burden, especially in patients with comorbidities. The management of comorbidities should be prioritized to mitigate poor health outcomes in infected individuals.
Radio-opaque contrast agents for liver cancer targeting with KIM during radiation therapy (ROCK-RT): an observational feasibility study
Authors: Plant Natalie , Mylonas Adam , Sengupta Chandrima , Nguyen Doan Trang , Silvester Shona , Pryor David , Greer Peter , Lee Yoo Young , Ramachandran Prabhakar , Seshadri Venkatakrishnan , Trada Yuvnik , Khor Richard , Wang Tim , Hardcastle Nicholas , Keall Paul
Published: October 2024

Background

This observational study aims to establish the feasibility of using x-ray images of radio-opaque chemoembolisation deposits in patients as a method for real-time image-guided radiation therapy of hepatocellular carcinoma.

Methods

This study will recruit 50 hepatocellular carcinoma patients who have had or will have stereotactic ablative radiation therapy and have had transarterial chemoembolisation with a radio-opaque agent. X-ray and computed tomography images of the patients will be analysed retrospectively. Additionally, a deep learning method for real-time motion tracking will be developed. We hypothesise that: (i) deep learning software can be developed that will successfully track the contrast agent mass on two thirds of cone beam computed tomography (CBCT) projection and intra-treatment images (ii), the mean and standard deviation (mm) difference in the location of the mass between ground truth and deep learning detection are ≤ 2 mm and ≤ 3 mm respectively and (iii) statistical modelling of study data will predict tracking success in 85% of trial participants.

Discussion

Developing a real-time tracking method will enable increased targeting accuracy, without the need for additional invasive procedures to implant fiducial markers.

Trial registration

Registered to ClinicalTrials.gov (NCT05169177) 12th October 2021.
Right thoracotomy with central cannulation for valve surgery: 10 years of experience
Authors: Sharma Anil , Dixit Sunil , Sharma Mohit , Mittal Sourabh , Shah Apurva , Goyal Shefali
Published: October 2024

Background

The aim of this study is to report the early outcomes of valvular heart surgeries performed via the right thoracotomy approach. While thoracotomy with femoro-femoral bypass is an established method for minimally invasive open-heart surgeries, thoracotomy with conventional cannulation is still being explored. In our center, we conducted 958 valvular heart surgery cases using the right anterolateral thoracotomy approach with central cannulation and data were analyzed.

Methods

This is a retrospective observational study based on prospectively collected data from patients who underwent valvular heart surgery at our center spanning from April 2013 to April 2023. The data encompass demographics, procedures, operative techniques, post-operative morbidity, mortality, and a 1-month follow-up.

Results

Our study revealed no procedure-related mortality. No patient required conversion to median sternotomy. Smooth cannulation and satisfactory exposure were achieved in all patients. The study encompassed a wide age range, from 14 to 68 years, with 618 female patients (64.5%) and 340 male patients (35.5%). The average cross-clamp time ranged from 38 to 90 min, the duration of cardio-pulmonary bypass ranged from 45 to 105 min, post-operative extubation ranged from 3 to 8 h, the average drain volume ranged from 100 to 350 ml, and the incision size ranged from 5 to 7 cm.

Conclusions

Our data demonstrate that conventional cannulation via the right antero-lateral thoracotomy approach for valvular heart disease is a viable alternative to reduce the side effects associated with sternotomy and femoral cannulation. This procedure is safe, reproducible, and provides the same level of treatment quality.
Puerarin: a hepatoprotective drug from bench to bedside
Authors: He Yi-Xiang , Liu Meng-Nan , Wu Hao , Lan Qi , Liu Hao , Mazhar Maryam , Xue Jin-Yi , Zhou Xin , Chen Hui , Li Zhi
Published: October 2024

Pueraria is a time-honored food and medicinal plant, which is widely used in China. Puerarin, the main component extracted from pueraria, has a variety of pharmacological characteristics. In recent years, puerarin has received increasing attention for its significant hepatoprotective effects, such as metabolic dysfunction-associated steatotic liver disease, alcohol-related liver disease, and hepatic carcinoma. This paper explores the pharmacological effects of puerarin on various liver diseases through multiple mechanisms, including inflammation factors, oxidative stress, lipid metabolism, apoptosis, and autophagy. Due to its restricted solubility, pharmacokinetic studies revealed that puerarin has a low bioavailability. However, combining puerarin with novel drug delivery systems can improve its bioavailability. Meanwhile, puerarin has very low toxicity and high safety, providing a solid foundation for its further. In addition, this paper discusses puerarin's clinical trials, highlighting its unique advantages. Given its excellent pharmacological effects, puerarin is expected to be a potential drug for the treatment of various liver diseases.
Clarifying the association of CSF Aβ, tau, BACE1, and neurogranin with AT(N) stages in Alzheimer disease
Authors: Lehmann Sylvain , Schraen-Maschke Susanna , Buée Luc , Vidal Jean-Sébastien , Delaby Constance , Hirtz Christophe , Blanc Frédéric , Paquet Claire , Allinquant Bernadette , Bombois Stéphanie , Gabelle Audrey , Hanon Olivier ,   for the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: October 2024

Background

Current AT(N) stratification for Alzheimer’s disease (AD) accounts for complex combinations of amyloid (A), tau proteinopathy (T) and neurodegeneration (N) signatures. Understanding the transition between these different stages is a major challenge, especially in view of the recent development of disease modifying therapy.

Methods

This is an observational study, CSF levels of Tau, pTau181, pTau217, Aβ38/40/42, sAPPα/β, BACE1 and neurogranin were measured in the BALTAZAR cohort of cognitively impaired patients and in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Biomarkers levels were related to the AT(N) framework. (A) and (T) were defined in BALTAZAR with CSF Aβ42/40 ratio and pTau217 respectively, and in ADNI with amyloid and tau PET. (N) was defined using total CSF tau in both cohorts.

Results

As expected, CSF Aβ42 decreased progressively with the AD continuum going from the A-T-N- to the A + T + N + profile. On the other hand, Tau and pTau181 increased progressively with the disease. The final transition from A + T + N- to A + T + N + led to a sharp increase in Aβ38, Aβ42 and sAPP levels. Synaptic CSF biomarkers BACE1 and neurogranin, were lowest in the initial A + T-N- stage and increased with T + and N + . CSF pTau181 and total tau were closely related in both cohorts.

Conclusions

The early transition to an A + phenotype (A + T-N-) primarily impacts synaptic function. The appearance of T + and then N + is associated with a significant and progressive increase in pathological Alzheimer's disease biomarkers. Our main finding is that CSF pTau181 is an indicator of N + rather than T + , and that N + is associated with elevated levels of BACE1 protein and beta-amyloid peptides. This increase may potentially fuel the amyloid cascade in a positive feedback loop. Overall, our data provide further insights into understanding the interconnected pathological processes of amyloid, tau, and neurodegeneration underlying Alzheimer's disease.
Integrated large-scale metagenome assembly and multi-kingdom network analyses identify sex differences in the human nasal microbiome
Authors: Ju Yanmei , Zhang Zhe , Liu Mingliang , Lin Shutian , Sun Qiang , Song Zewei , Liang Weiting , Tong Xin , Jie Zhuye , Lu Haorong , Cai Kaiye , Chen Peishan , Jin Xin , Zhang Wenwei , Xu Xun , Yang Huanming , Wang Jian , Hou Yong , Xiao Liang , Jia Huijue , Zhang Tao , Guo Ruijin
Published: October 2024

Background

Respiratory diseases impose an immense health burden worldwide. Epidemiological studies have revealed extensive disparities in the incidence and severity of respiratory tract infections between men and women. It has been hypothesized that there might also be a nasal microbiome axis contributing to the observed sex disparities.

Results

Here, we study the nasal microbiome of healthy young adults in the largest cohort to date with 1593 individuals, using shotgun metagenomic sequencing. We compile the most comprehensive reference catalog for the nasal bacterial community containing 4197 metagenome-assembled genomes and integrate the mycobiome, to provide a valuable resource and a more holistic perspective for the understudied human nasal microbiome. We systematically evaluate sex differences and reveal extensive sex-specific features in both taxonomic and functional levels in the nasal microbiome. Through network analyses, we capture markedly higher ecological stability and antagonistic potentials in the female nasal microbiome compared to the male’s. The analysis of the keystone bacteria reveals that the sex-dependent evolutionary characteristics might have contributed to these differences.

Conclusions

In summary, we construct the most comprehensive catalog of metagenome-assembled-genomes for the nasal bacterial community to provide a valuable resource for the understudied human nasal microbiome. On top of that, comparative analysis in relative abundance and microbial co-occurrence networks identify extensive sex differences in the respiratory tract community, which may help to further our understanding of the observed sex disparities in the respiratory diseases.
Superior temporal sulcus folding, functional network connectivity, and autistic-like traits in a non-clinical population
Authors: Nenadić Igor , Schröder Yvonne , Hoffmann Jonas , Evermann Ulrika , Pfarr Julia-Katharina , Bergmann Aliénor , Hohmann Daniela Michelle , Keil Boris , Abu-Akel Ahmad , Stroth Sanna , Kamp-Becker Inge , Jansen Andreas , Grezellschak Sarah , Meller Tina
Published: October 2024

Background

Autistic-like traits (ALT) are prevalent across the general population and might be linked to some facets of a broader autism spectrum disorder (ASD) phenotype. Recent studies suggest an association of these traits with both genetic and brain structural markers in non-autistic individuals, showing similar spatial location of findings observed in ASD and thus suggesting a potential neurobiological continuum.

Methods

In this study, we first tested an association of ALTs (assessed with the AQ questionnaire) with cortical complexity, a cortical surface marker of early neurodevelopment, and then the association with disrupted functional connectivity. We analysed structural T1-weighted and resting-state functional MRI scans in 250 psychiatrically healthy individuals without a history of early developmental disorders, in a first step using the CAT12 toolbox for cortical complexity analysis and in a second step we used regional cortical complexity findings to apply the CONN toolbox for seed-based functional connectivity analysis.

Results

Our findings show a significant negative correlation of both AQ total and AQ attention switching subscores with left superior temporal sulcus (STS) cortical folding complexity, with the former being significantly correlated with STS to left lateral occipital cortex connectivity, while the latter showed significant positive correlation of STS to left inferior/middle frontal gyrus connectivity (n = 233; all p < 0.05, FWE cluster-level corrected). Additional analyses also revealed a significant correlation of AQ attention to detail subscores with STS to left lateral occipital cortex connectivity.

Limitations

Phenotyping might affect association results (e.g. choice of inventories); in addition, our study was limited to subclinical expressions of autistic-like traits.

Conclusions

Our findings provide further evidence for biological correlates of ALT even in the absence of clinical ASD, while establishing a link between structural variation of early developmental origin and functional connectivity.
Genetically engineered human induced pluripotent stem cells for the production of brain-targeting extracellular vesicles
Authors: Tang Fan , Dong Tao , Zhou Chengqian , Deng Leon , Liu Hans B. , Wang Wenshen , Liu Guanshu , Ying Mingyao , Li Pan P.
Published: October 2024

Background

Extracellular vesicles (EVs) are cell-secreted membrane vesicles that have become a promising, natural nanoparticle system for delivering either naturally carried or exogenously loaded therapeutic molecules. Among reported cell sources for EV manufacture, human induced pluripotent stem cells (hiPSCs) offer numerous advantages. However, hiPSC-EVs only have a moderate ability for brain delivery. Herein, we sought to develop a stable hiPSC line for producing EVs with substantially enhanced brain targeting by genetic engineering to overexpress rabies viral glycoprotein (RVG) peptide fused to the N terminus of lysosomal associated membrane protein 2B (RVG-Lamp2B) which has been shown capable of boosting the brain delivery of EVs via the nicotinic acetylcholine receptor.

Methods

An RVG-Lamp2B-HA expression cassette was knocked into the AAVS1 safe harbor locus of a control hiPSC line using the CRISPR/Cas9-assisted homologous recombination. Western blot was used to detect the expression of RVG-Lamp2B-HA in RVG-edited hiPSCs as well as EVs derived from RVG-edited hiPSCs. Uptake of EVs by SH-SY5Y cells in the presence of various endocytic inhibitors was analyzed using flow cytometry. Biodistribution and brain delivery of intravenously injected control and RVG-modified EVs in wild-type mice were examined using ex vivo fluorescent imaging.

Results

Here we report that an RVG-Lamp2B-HA expression cassette was knocked into the AAVS1 safe harbor locus of a control hiPSC line using the CRISPR/Cas9-assisted homologous recombination. The RVG-edited iPSCs have normal karyotype, express pluripotency markers, and have differentiation potential. Expression of RVG-Lamp2B-HA was detected in total cell extracts as well as EVs derived from RVG-edited (vs. control) hiPSCs. The RVG-modified EVs enter neuronal cells via distinct endocytic pathways, compared with control EVs. The biodistribution study confirmed that EVs derived from RVG-edited hiPSCs possess higher brain delivery efficiency.

Conclusion

Taken together, we have established stable, genetically engineered hiPSCs for producing EVs with RVG expression, offering the improved ability for brain-targeted drug delivery.
Vasoactive intestinal peptide promotes secretory differentiation and mitigates radiation-induced intestinal injury
Authors: Agibalova Tatiana , Hempel Anneke , Maurer H. Carlo , Ragab Mohab , Ermolova Anastasia , Wieland Jessica , Waldherr Ávila de Melo Caroline , Heindl Fabian , Giller Maximilian , Fischer Julius Clemens , Tschurtschenthaler Markus , Kohnke-Ertel Birgit , Öllinger Rupert , Steiger Katja , Demir Ihsan Ekin , Saur Dieter , Quante Michael , Schmid Roland M. , Middelhoff Moritz
Published: October 2024

Background

Vasoactive intestinal peptide (VIP) is a neuronal peptide with prominent distribution along the enteric nervous system. While effects of VIP on intestinal motility, mucosal vasodilation, secretion, and mucosal immune cell function are well-studied, the direct impact of VIP on intestinal epithelial cell turnover and differentiation remains less understood. Intestinal stem and progenitor cells are essential for the maintenance of intestinal homeostasis and regeneration, and their functions can be modulated by factors of the stem cell niche, including neuronal mediators. Here, we investigated the role of VIP in regulating intestinal epithelial homeostasis and regeneration following irradiation-induced injury.

Methods

Jejunal organoids were derived from male and female C57Bl6/J, Lgr5-EGFP-IRES-CreERT2 or Lgr5-EGFP-IRES-CreERT2/R26R-LSL-TdTomato mice and treated with VIP prior to analysis. Injury conditions were induced by exposing organoids to 6 Gy of irradiation (IR). To investigate protective effects of VIP in vivo, mice received 12 Gy of abdominal IR followed by intraperitoneal injections of VIP.

Results

We observed that VIP promotes epithelial differentiation towards a secretory phenotype predominantly via the p38 MAPK pathway. Moreover, VIP prominently modulated epithelial proliferation as well as the number and proliferative activity of Lgr5-EGFP+ progenitor cells under homeostatic conditions. In the context of acute irradiation injury in vitro, we observed that IR injury renders Lgr5-EGFP+ progenitor cells more susceptible to VIP-induced modulations, which coincided with the strong promotion of epithelial regeneration by VIP. Finally, the observed effects translate into an in vivo model of abdominal irradiation, where VIP showed to prominently mitigate radiation-induced injury.

Conclusions

VIP prominently governs intestinal homeostasis by regulating epithelial progenitor cell proliferation and differentiation and promotes intestinal regeneration following acute irradiation injury.
[18F]TFB PET/CT misses intense [124I]iodine-avid metastases after redifferentiation therapy in metastatic thyroid cancer
Authors: Backhaus Philipp , Pentlow Keith S. , Ho Alan L , Mauguen Audrey , Fagin James A , Pillarsetty Naga Vara Kishore , Lyashchenko Serge K. , Burnazi Eva , Ghossein Ronald A. , Chhabra Shalini , Abusamra Murad , Larson Steven M. , Schöder Heiko , O’Donoghue Joseph , Weber Wolfgang , Grewal Ravinder K.
Published: October 2024

Background

Fluorine 18-labelled tetrafluoroborate ([18F]TFB) is a substrate for the sodium/iodide symporter. In thyroid cancer, [18F]TFB-PET/CT may be an alternative to iodine imaging to evaluate the extent of disease, eligibility for radioiodine treatment, and success of redifferentiation therapies. We report the results of a pilot study to determine tumor uptake of [18F]TFB and compare its properties to [124I]IodinePET/CT in patients with metastatic thyroid cancer.

Methods

Five patients were included in a prospective study. All patients received PET/CT 1 h after injection of 356 ± 12 MBq [18F]TFB and were given 230 ± 9 MBq [124I]Iodine orally on the same day, followed by PET/CT after 48 h. Before redifferentiation therapy, patients underwent an additional baseline [124I]Iodine PET/CT. Cases were analyzed by two board-certified specialists. Detection rates and Spearman correlation for [18F]TFB and [124I]Iodine were calculated.

Results

Three patients had poorly differentiated thyroid cancer and received trametinib in a redifferentiation trial. Two patients had papillary thyroid cancer and did not receive redifferentiation therapy. Of the 33 lesions seen before/without redifferentiation therapy, 19 (58%) were visible on [18F]TFB and 30 (91%) on [124I]Iodine imaging. In the patients who underwent redifferentiation therapy, 48 lesions were newly seen on [124I]Iodine PET/CT with a median SUVmax of 3.3 (range, 0.4–285.0). All of these lesions were [18F]TFB-negative.

Conclusion

[18F]TFB failed to predict radioactive iodine uptake in patients with poorly differentiated thyroid cancer who underwent redifferentiation therapy with trametinib. It is unclear whether such discrepancies may also occur in other redifferentiation therapies or may even be encountered in redifferentiation-naïve thyroid cancer.

Trial registration number

NCT03196518, registered on June 22, 2017.
Heparin does not improve myocardial glucose metabolism suppression in [18 F]FDG PET/CT in patients with low β-hydroxybutyrate level
Authors: Hartikainen Suvi , Vepsäläinen Ville , Laitinen Tiina , Hedman Marja , Laitinen Tomi , Tompuri Tuomo
Published: October 2024

Background

Inadequate myocardial glucose metabolism suppression (GMS) can hamper interpretation of cardiac [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). Use of β-hydroxybutyrate (BHB) measurement before [18F]FDG injection has been proposed for predicting adequate GMS. However, limited information is available on BHB measurement in guiding preparations for [18F]FDG-PET/CT. The purpose of this study was to evaluate if point-of-care measured BHB is useful in guiding heparin premedication for cardiac [18F]FDG-PET/CT.

Results

155 patients (82 male) had followed a high-fat, low-carbohydrate diet and fasted for at least twelve hours. For the first 63 patients, BHB was measured, but it was not used to guide premedication. For the subsequent 92 patients, heparin 50 IU/kg was injected intravenously 15–20 min before [18F]FDG injection if the BHB level was low (< 0.35 mmol/l). Cardiac [18F]FDG uptake pattern was evaluated visually and [18F]FDG uptake in the myocardium and blood pool were measured. Median BHB level was 0.4 (range 0.1–5.8) mmol/l. Eighty-eight patients (57%) reached a BHB level higher than 0.35 mmol/l. 112 patients (72%) had adequate GMS. In the high BHB group, 74 patients (84%) had adequate GMS, whereas of those with low BHB, only 38 (57%) had adequate GMS (p < 0.001). In the low BHB group, the prevalence of inadequate GMS was comparable in patients with and without heparin (44% vs. 42%, p = 0.875).

Conclusions

While high BHB predicts adequate GMS, unfractionated heparin does not improve GMS in patients with low BHB.
DOA-informed switching independent vector extraction and beamforming for speech enhancement in underdetermined situations
Authors: Ueda Tetsuya , Nakatani Tomohiro , Ikeshita Rintaro , Araki Shoko , Makino Shoji
Published: October 2024

This paper proposes novel methods for extracting a single Speech signal of Interest (SOI) from a multichannel observed signal in underdetermined situations, i.e., when the observed signal contains more speech signals than microphones. It focuses on extracting the SOI using prior knowledge of the SOI’s Direction of Arrival (DOA). Conventional beamformers (BFs) and Blind Source Separation (BSS) with spatial regularization struggle to suppress interference speech signals in such situations. Although Switching Minimum Power Distortionless Response BF (Sw-MPDR) can handle underdetermined situations using a switching mechanism, its estimation accuracy significantly decreases when it relies on a steering vector determined by the SOI’s DOA. Spatially-Regularized Independent Vector Extraction (SRIVE) can robustly enhance the SOI based solely on its DOA using spatial regularization, but its performance degrades in underdetermined situations. This paper extends these conventional methods to overcome their limitations. First, we introduce a time-varying Gaussian (TVG) source model to Sw-MPDR to effectively enhance the SOI based solely on the DOA. Second, we introduce the switching mechanism to SRIVE to improve its speech enhancement performance in underdetermined situations. These two proposed methods are called Switching weighted MPDR (Sw-wMPDR) and Switching SRIVE (Sw-SRIVE). We experimentally demonstrate that both surpass conventional methods in enhancing the SOI using the DOA in underdetermined situations.
Analysing the robustness of finger vein recognition: cross-dataset reliability and vein utility
Authors: Arican Tugce , Veldhuis Raymond , Spreeuwers Luuk
Published: October 2024

Finger vein recognition is an emerging biometric trait known for its privacy features. Despite the remarkable performance of deep learning methods like convolutional neural networks on challenging finger vein datasets, their reliability and robustness need further examination. This study evaluates the robustness of three recognition methods—the traditional Miura Method, a supervised convolutional neural network, and an unsupervised convolutional auto-encoder—through the challenging and more realistic scenario of cross-dataset comparisons. We also analyse the reliability of these methods in terms of sample quality. We introduce a novel vein quality metric to measure vein clarity and complexity and compare it against an existing image quality metric, natural image quality evaluator. Our findings reveal differences in how these recognition methods utilise finger vein images for comparisons, highlighting the need for robust recognition techniques in more realistic scenarios. In addition, our vein quality metric effectively detects defective images, reducing the zero false-match rate from 34.98% to 8.18% on the SDUMLA-HMT dataset. These results indicate the need for metrics more focussing on finger vein image characteristics for effective quality assessment for finger vein images.
$$\text {CO}_2$$-based methane: an overlooked solution for the energy transition
Authors: Servin-Balderas Ivonne , Wetser Koen , ter Heijne Annemiek , Buisman Cees , Hamelers Bert
Published: October 2024

Background

Fossil fuels can be replaced with electricity and hydrogen. However, the implementation and use of these low-carbon energy carriers require a sociotechnical transition. This transition might not be completed in time.

Main text

$$\text {CO}_2$$

CO
2

-based methane is a substitute for natural gas that is less carbon-intensive. This methane is synthesized by capturing $$\text {CO}_2$$

CO
2

from air and by performing water electrolysis to produce hydrogen. $$\text {CO}_2$$

CO
2

-based methane is compatible with our current fossil-based society. An analysis of the substitution of natural gas with different energy carriers will be performed, and the results will be compared. The effects of $$\text {CO}_2$$

CO
2

-based methane, hydrogen, and electricity will be evaluated for energy storage, high-temperature level heat production, and residential heating. The multi-level perspective will be applied to assess these energy carriers in the context of our society.

Conclusions

$$\text {CO}_2$$

CO
2

-based methane is the least energy efficient energy carrier among those analyzed. Nevertheless, this type of methane supports the acceleration of the energy transition.

Highlights

CO2-based methane is a valuable, renewable, and carbon-neutral energy carrier that supports a timely energy transition.

The implementation of hydrogen and electricity requires more modifications to our current sociotechnical society than the implementation of CO2-based methane.

The urgency of reducing CO2 emissions is not being considered adequately in the current societal discussion, and a multi-level perspective analysis should provide valuable results that account for the temporal aspect.