bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma biomarkers increase diagnostic confidence in patients with Alzheimer’s disease or frontotemporal lobar degeneration
Authors: Altomare Daniele , Libri Ilenia , Alberici Antonella , Rivolta Jasmine , Padovani Alessandro , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Borroni Barbara 
Published: May 2024

Abstract
Background
The recent development of techniques to assess plasma biomarkers has changed the way the research community envisions the future of diagnosis and management of Alzheimer’s disease (AD) and other neurodegenerative disorders. This work aims to provide real world evidence on the clinical impact of plasma biomarkers in an academic tertiary care center.

Methods
Anonymized clinical reports of patients diagnosed with AD or Frontotemporal Lobar Degeneration with available plasma biomarkers (Aβ42, Aβ42/Aβ40, p-tau181, p-tau231, NfL, GFAP) were independently assessed by two neurologists who expressed diagnosis and diagnostic confidence three times: (T0) at baseline based on the information collected during the first visit, (T1) after plasma biomarkers, and (T2) after traditional biomarkers (when available). Finally, we assessed whether clinicians’ interpretation of plasma biomarkers and the consequent clinical impact are consistent with the final diagnosis, determined after the conclusion of the diagnostic clinical and instrumental work-up by the actual managing physicians who had complete access to all available information.

Results
Clinicians assessed 122 reports, and their concordance ranged from 81 to 91% at the three time points. At T1, the presentation of plasma biomarkers resulted in a change of diagnosis in 2% (2/122, p = 1.00) of cases, and in increased diagnostic confidence in 76% (91/120, p < 0.001) of cases with confirmed diagnosis. The change in diagnosis and the increase in diagnostic confidence after plasma biomarkers were consistent with the final diagnosis in 100% (2/2) and 81% (74/91) of cases, respectively. At T2, the presentation of traditional biomarkers resulted in a further change of diagnosis in 13% (12/94, p = 0.149) of cases, and in increased diagnostic confidence in 88% (72/82, p < 0.001) of cases with confirmed diagnosis.

Conclusions
In an academic tertiary care center, plasma biomarkers supported clinicians by increasing their diagnostic confidence in most cases, despite a negligible impact on diagnosis. Future prospective studies are needed to assess the full potential of plasma biomarkers on clinical grounds.
Serum urate levels and neurodegenerative outcomes: a prospective cohort study and mendelian randomization analysis of the UK Biobank
Authors: Zhang Tingjing , An Yu , Shen Zhenfei , Yang Honghao , Jiang Jinguo , Chen Liangkai , Lu Yanhui , Xia Yang 
Published: May 2024

Abstract
Background
Previous studies on the associations between serum urate levels and neurodegenerative outcomes have yielded inconclusive results, and the causality remains unclear. This study aimed to investigate whether urate levels are associated with the risks of Alzheimer’s disease and related dementias (ADRD), Parkinson’s disease (PD), and neurodegenerative deaths.

Methods
This prospective study included 382,182 participants (45.7% men) from the UK Biobank cohort. Cox proportional hazards models were used to assess the associations between urate levels and risk of neurodegenerative outcomes. In the Mendelian randomization (MR) analysis, urate-related single-nucleotide polymorphisms were identified through a genome-wide association study. Both linear and non-linear MR approaches were utilized to investigate the potential causal associations.

Results
During a median follow-up period of 12 years, we documented 5,400 ADRD cases, 2,553 PD cases, and 1,531 neurodegenerative deaths. Observational data revealed that a higher urate level was associated with a decreased risk of ADRD (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.90, 0.96), PD (HR: 0.87, 95% CI: 0.82, 0.91), and neurodegenerative death (HR: 0.88, 95% CI: 0.83, 0.94). Negative linear associations between urate levels and neurodegenerative events were observed (all P-values for overall < 0.001 and all P-values for non-linearity > 0.05). However, MR analyses yielded no evidence of either linear or non-linear associations between genetically predicted urate levels and the risk of the aforementioned neurodegenerative events.

Conclusion
Although the prospective cohort study demonstrated that elevated urate levels were associated with a reduced risk of neurodegenerative outcomes, MR analyses found no evidence of causality.
Unusual phenotype in 35delG mutation: a case report
Authors: Yeral Cem , Seneldir Lutfu , Karakoc Arzu Hediye , Sap Aleyna , Yilmaz Oguz 
Published: May 2024

Abstract
Background
Mutations in the GJB2 gene, which encodes the protein connexin 26 and is involved in inner ear homeostasis, are identified in approximately 50% of patients with autosomal recessive nonsyndromic hearing loss, making it one of the primary causes of prelingual nonsyndromic hearing loss in various populations. The 35delG mutation, one of the most common mutations of the GJB2 gene, usually causes prelingual, bilateral mild to profound, nonprogressive sensorineural hearing loss.

Case presentation
We present an unusual case of an 18-year-old Turkish female with heterozygous 35delG mutation and postlingual, profound-sloping, progressive and fluctuating unilateral sensorineural hearing loss. The phenotype is different from the usual findings.

Conclusions
The 35delG mutation causing hearing loss may not always be reflected in the phenotype as expected and therefore may have different audiologic manifestations.
Resilient data-driven non-intrusive load monitoring for efficient energy management using machine learning techniques
Authors: Nutakki Mounica , Mandava Srihari 
Published: May 2024

AbstractThe integration of smart homes into smart grids presents numerous challenges, particularly in managing energy consumption efficiently. Non-intrusive load management (NILM) has emerged as a viable solution for optimizing energy usage. However, as smart grids incorporate more distributed energy resources, the complexity of demand-side management and energy optimization escalates. Various techniques have been proposed to address these challenges, but the evolving grid necessitates intelligent optimization strategies. This article explores the potential of data-driven NILM (DNILM) by leveraging multiple machine learning algorithms and neural network architectures for appliance state monitoring and predicting future energy consumption. It underscores the significance of intelligent optimization techniques in enhancing prediction accuracy. The article compares several data-driven mechanisms, including decision trees, sequence-to-point models, denoising autoencoders, recurrent neural networks, long short-term memory, and gated recurrent unit models. Furthermore, the article categorizes different forms of NILM and discusses the impact of calibration and load division. A detailed comparative analysis is conducted using evaluation metrics such as root-mean-square error, mean absolute error, and accuracy for each method. The proposed DNILM approach is implemented using Python 3.10.5 on the REDD dataset, demonstrating its effectiveness in addressing the complexities of energy optimization in smart grid environments.
Stable carbon isotope composition and intrinsic water use efficiency in plants along an altitudinal gradient on the eastern slope of Yulong Snow Mountain, China
Authors: Jiang Feng , Pu Tao , Xue Zi-Jing , Ma Yan-Wei , Shi Xiao-Yi , Shi Fu-Xi 
Published: May 2024

Abstract
Background
Stable carbon isotope composition (δ13Cp) can be used to estimate the changes in intrinsic water use efficiency (iWUE) in plants, which helps us to better understand plants’ response strategies to climate change. This study focused on the variations in δ13Cp and iWUE for the different life-form plants (i.e., herbs, shrubs, and trees) along an altitudinal gradient (3300, 3600, 3900, 4100, 4300, and 4500 m) on the eastern slope of Yulong Snow Mountain, southeastern margin of the Qinghai-Tibet Plateau. The response mechanisms of δ13Cp and iWUE for different life-form plants to altitude were thoroughly analyzed in this mountain ecosystem.

Results
The δ13Cp values of plants on the eastern slopes of Yulong Snow Mountain ranged from − 30.4‰ to − 26.55‰, with a mean of − 28.02‰, indicating a dominance of C3 plants. The δ13Cp and iWUE values varied among different life-form plants in the order of herbs > shrubs > trees, particularly in 3600, 3900, and 4300 m. The δ13Cp and iWUE values for herbs and shrubs increased with altitude and were mainly controlled by air temperature. The two parameters for trees exhibited a trend of initial decrease followed by an increase with altitude. Below 3900 m, the δ13Cp and iWUE values decreased with altitude, influenced by soil moisture. However, above 3900 m, the two parameters increased with altitude, mainly regulated by air temperature. In addition, iWUE was positively correlated with leaf P content but negatively correlated with leaf N:P ratio, especially for herbs and trees, suggesting that P plays a key role in modulating iWUE in this region.

Conclusions
The differentiated responses of water availability for different life-form plants to a higher altitudinal gradient are regulated by air temperature, soil moisture, and leaf P content in the Yulong Snow Mountain. These results provide valuable insights into understanding the water–carbon relationships in high-altitude ecosystems.
Teaching prudent antibiotic use on the go: a descriptive report on development, utilization and listener satisfaction of an educational podcast format for medical students and young professionals
Authors: Schneider Sandra , Bergmann Clara , Becker Felicia , Risse Lukas , Isner Caroline , Stocker Hartmut , Feufel Markus A. , Röhrig Alina , Kurzai Oliver , Lâm Thiên-Trí , Hagel Stefan , Pletz Mathias W. , Gastmeier Petra , Wiese-Posselt Miriam 
Published: May 2024

Abstract
Background
An important component in fostering the responsible use of antibiotics is training of new and future prescribers in this interdisciplinary topic. Because podcasts are playing an increasing role in medical education, we aimed to develop and evaluate a podcast format with practice and guideline-oriented learning content on antibiotic therapy for medical students and young medical professionals.

Methods
We developed the concept for the podcast with the direct involvement of medical students and medical experts with teaching experience. We used video conferencing when recording the episodes in order to have quick, easy, and nationwide access to the experts involved. We released an episode every 2 to 4 weeks on the popular podcast platforms. The podcast was promoted through mailing lists, social and print media, and at conferences. The evaluation of episodes was based on user data provided by the platforms and an anonymous feedback questionnaire linked to each episode in the podcast notes.

Results
Between December 2021 and December 2022 19 episodes of InfectEd: der Antibiotika-Podcast were released. The mean duration of an episode was 91 min. By March 9, 2023, a total of 38,829 downloads and streams had been recorded. The majority of users listened to the podcast on a mobile device. The average playing time per episode was 65%. The feedback questionnaire was completed 135 times. 60.7% of respondents were female, 38.5% male. The majority of respondents were in their twenties and thirties (66.7%). 31.1% were medical students, 25.9% were residents, and 25.2% were specialists. Listeners were asked to rate episodes on a scale from 1 to 6, where 1 was “very good” and 6 was “insufficient.” Ratings did not differ significantly between female and male respondents or between medical students and others. 118 respondents (87.4%) reported an increase in knowledge. Free-text feedback frequently emphasized clinical and also exam relevance.

Conclusion
Our podcast format, developed with a user-centered approach, was broadly distributed and has been well accepted by both medical students and physicians alike. It provides a large number of learners with low-threshold access to current, guideline-orientated content and could be a useful supplement to conventional teaching formats.
Highly immunosuppressive myeloid cells correlate with early relapse after allogeneic stem cell transplantation
Authors: Notarantonio Anne-Béatrice , Bertrand Allan , Piucco Romain , Fievet Ghislain , Sartelet Hervé , Boulangé Laura , de Isla Natalia , De Carvalho Bittencourt Marcelo , Hergalant Sébastien , Rubio Marie-Thérèse , D’Aveni Maud 
Published: May 2024

Abstract
Background
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only curative treatment for myeloid malignancies such as some acute myeloid leukemias (AML) and high-risk myelodysplastic syndromes (MDS). It aims to eradicate the malignant clone using immunocompetent donor cells (graft-versus-leukemia effect, GVL). Unfortunately, relapse is the primary cause of transplant failure mainly related on HLA loss or downregulation and upregulation of inhibitory ligands on blasts which result in donor immune effector dysfunctions.

Methods
Between 2018 and 2021, we conducted a monocentric prospective study including 61 consecutive patients transplanted for AML or high-risk MDS. We longitudinally investigated immune cells at days + 30, + 90 and + 180 post-transplant from bone marrow and peripheral blood. We assessed the dynamics between myeloid derived suppressor cells (MDSCs) and T-cells.

Results
Among the 61 patients, 45 did not relapse over the first 12 months while 16 relapsed during the first year post-transplant. Through months 1 to 6, comparison with healthy donors revealed an heterogenous increase in MDSC frequency. In all recipients, the predominant MDSC subset was granulocytic with no specific phenotypic relapse signature. However, in relapsed patients, in vitro and in vivo functional analyses revealed that MDSCs from peripheral blood were highly immunosuppressive from day + 30 onwards, with an activated NLRP3 inflammasome signature. Only circulating immunosuppressive MDSCs were statistically correlated to circulating double-positive Tim3+LAG3+ exhausted T cells.

Conclusion
Our simple in vitro functional assay defining MDSC immunosuppressive properties might serve as an early biomarker of relapse and raise the question of new preventive treatments targeting MDSCs in the future.
Trial registrationNCT03357172
Deciphering metabolic heterogeneity in retinoblastoma unravels the role of monocarboxylate transporter 1 in tumor progression
Authors: Tang Junjie , Liu Yaoming , Wang Yinghao , Zhang Zhihui , Nie Jiahe , Wang Xinyue , Ai Siming , Li Jinmiao , Gao Yang , Li Cheng , Cheng Chao , Su Shicai , Chen Shuxia , Zhang Ping , Lu Rong 
Published: May 2024

Abstract
Background
Tumors exhibit metabolic heterogeneity, influencing cancer progression. However, understanding metabolic diversity in retinoblastoma (RB), the primary intraocular malignancy in children, remains limited.

Methods
The metabolic landscape of RB was constructed based on single-cell transcriptomic sequencing from 11 RB and 5 retina samples. Various analyses were conducted, including assessing overall metabolic activity, metabolic heterogeneity, and the correlation between hypoxia and metabolic pathways. Additionally, the expression pattern of the monocarboxylate transporter (MCT) family in different cell clusters was examined. Validation assays of MCT1 expression and function in RB cell lines were performed. The therapeutic potential of targeting MCT1 was evaluated using an orthotopic xenograft model. A cohort of 47 RB patients was analyzed to evaluate the relationship between MCT1 expression and tumor invasion.

Results
Distinct metabolic patterns in RB cells, notably increased glycolysis, were identified. This metabolic heterogeneity correlated closely with hypoxia. MCT1 emerged as the primary monocarboxylate transporter in RB cells. Disrupting MCT1 altered cell viability and energy metabolism. In vivo studies using the MCT1 inhibitor AZD3965 effectively suppressed RB tumor growth. Additionally, a correlation between MCT1 expression and optic nerve invasion in RB samples suggested prognostic implications.

Conclusions
This study enhances our understanding of RB metabolic characteristics at the single-cell level, highlighting the significance of MCT1 in RB pathogenesis. Targeting MCT1 holds promise as a therapeutic strategy for combating RB, with potential prognostic implications.
Mechanisms maintaining right ventricular contractility-to-pulmonary arterial elastance ratio in VA ECMO: a retrospective animal data analysis of RV–PA coupling
Authors: Bachmann Kaspar F. , Moller Per Werner , Hunziker Lukas , Maggiorini Marco , Berger David 
Published: May 2024

Abstract
Background
To optimize right ventricular–pulmonary coupling during veno-arterial (VA) ECMO weaning, inotropes, vasopressors and/or vasodilators are used to change right ventricular (RV) function (contractility) and pulmonary artery (PA) elastance (afterload). RV–PA coupling is the ratio between right ventricular contractility and pulmonary vascular elastance and as such, is a measure of optimized crosstalk between ventricle and vasculature. Little is known about the physiology of RV–PA coupling during VA ECMO. This study describes adaptive mechanisms for maintaining RV–PA coupling resulting from changing pre- and afterload conditions in VA ECMO.

Methods
In 13 pigs, extracorporeal flow was reduced from 4 to 1 L/min at baseline and increased afterload (pulmonary embolism and hypoxic vasoconstriction). Pressure and flow signals estimated right ventricular end-systolic elastance and pulmonary arterial elastance. Linear mixed-effect models estimated the association between conditions and elastance.

Results
At no extracorporeal flow, end-systolic elastance increased from 0.83 [0.66 to 1.00] mmHg/mL at baseline by 0.44 [0.29 to 0.59] mmHg/mL with pulmonary embolism and by 1.36 [1.21 to 1.51] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Pulmonary arterial elastance increased from 0.39 [0.30 to 0.49] mmHg/mL at baseline by 0.36 [0.27 to 0.44] mmHg/mL with pulmonary embolism and by 0.75 [0.67 to 0.84] mmHg/mL with hypoxic pulmonary vasoconstriction (p < 0.001). Coupling remained unchanged (2.1 [1.8 to 2.3] mmHg/mL at baseline; − 0.1 [− 0.3 to 0.1] mmHg/mL increase with pulmonary embolism; − 0.2 [− 0.4 to 0.0] mmHg/mL with hypoxic pulmonary vasoconstriction, p > 0.05). Extracorporeal flow did not change coupling (0.0 [− 0.0 to 0.1] per change of 1 L/min, p > 0.05). End-diastolic volume increased with decreasing extracorporeal flow (7.2 [6.6 to 7.8] ml change per 1 L/min, p < 0.001).

Conclusions
The right ventricle dilates with increased preload and increases its contractility in response to afterload changes to maintain ventricular–arterial coupling during VA extracorporeal membrane oxygenation.
Secondary ileal lymph node metastases from rectal cancer: a case report
Authors: Ando Makoto , Takemura Nobuyuki , Oikawa Ryo , Yoshizaki Yuhi , Inagaki Fuyuki , Mihara Fuminori , Kiyomatsu Tomomichi , Yamada Kazuhiko , Kokudo Norihiro 
Published: May 2024

Abstract
Background
Colorectal cancer can invade adjacent organs, but rarely metastasizes to the regional lymph nodes (LNs) of the invaded organ. Herein, we report a case of rectal cancer invading the ileum and metastasized to the regional ileal LNs.

Case presentation
A 77-year-old male presented abdominal pain and anorexia, diagnosed with rectal cancer invading the small intestine and concurrently metastasized to the regional LN of the intestine and liver. High anterior resection and partial resection of the small intestine was performed, then, the patient was referred to our hospital for chemotherapy. We performed 17 cycles of systemic chemotherapy that achieved a partial reduction in size of the LN, followed by an ileocecal resection with ileal mesentery resection for regional LNs removal. Histopathological analysis of the resected ileal LNs and six liver lesions revealed a moderately differentiated tubular adenocarcinoma. The patient was discharged on postoperative day 18. Cancer recurrences developed in the lungs 5 months after the surgery, then to the liver and peritoneum, and further surgery and chemotherapy were performed. Despite the challenging presentation, the patient survived for 40 months after the first surgery.

Conclusions
We report a rare case of a surgical resection of a secondary ileal LN metastasis from rectal cancer. The patient survives for a relatively long time after surgical resection. When colorectal cancer invades the small intestine, clinicians should consider the possibility of secondary LN metastasis in the invaded site.
HIF-1α facilitates glioma proliferation and invasion by activating pyroptosis signaling axis
Authors: Wang Xin-Wei , Fu Hao , Zhang Ya-Min 
Published: May 2024

Abstract
Background
HIF-1α is thought to be a novel regulator which contributes to carcinogenesis. However, the mechanism underlying the effect of HIF-1α in gliomas remains largely unknown.

Methods
In the research, we demonstrate that HIF-lα mRNA and protein levels are elevated in glioma cells. The colony formation assays, transwell assays, and wound-healing assays showed that overexpression of HIF-1α promoted proliferation and invasion of glioma cells.

Results
Overexpression of HIF-lα also increased the expression of inflammatory factors related to pyrolysis (TNF-α, IL-10, and IL-1β) and protein related to pyrolysis signal pathway (NLRP3, ASC, caspase-1, GSDMD, and GSDME).

Conclusions
Therefore, we speculate that HIF-1α promotes the proliferation and invasion of glial cells by regulating pyrolysis pathway. These results might provide a novel strategy and target for treatment of glioma.