bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functioning of a canopy-dominated intertidal community during emersion: highly productive but heterotrophic at the annual scale
Authors: Golléty Claire , Yearsley Jon , Migné Aline , Davoult Dominique 
Published: March 2024

AbstractIn order to address lack of data regarding coastal carbon budgets, we estimated the annual metabolic carbon budget of an intertidal rocky reef macroalgal community during emersion. This budget is based on direct in situ measurements during emersion and establishes the seasonal variations of the photosynthetic parameters of such a community. CO2 fluxes were measured hourly to study the response of community gross primary productivity (GPP) to irradiance and the variation of GPP and community respiration (CR) over the emersion period at different times of the year. These were combined together with existing monthly measures of GPP and CR hourly rates to model the variations of these fluxes as a function of irradiance and the tidal cycle throughout an entire calendar year. Daily, monthly and annual values of GPP, CR and net primary productivity (NPP) were calculated with a relatively low sensitivity to any of the parameters used. While GPP fluxes show comparable orders of magnitude to those measured in other systems, higher CR fluxes lead to a heterotrophic system during emersion, both under measured (NPP = −299 gC m−2 year−1) and theoretical irradiances (NPP = −119 gC m−2 year−1). This heterotrophy is directly linked to the light availability, varying according to combined daily, tidal and seasonal cycles, and to temperature at the seasonal scale. Measurements performed in situ at the community scale integrated interactions that are otherwise absent at the individual scale. This gives access to aspects of the functioning that cannot be otherwise identified.
An encoding of the $$\lambda $$-calculus in the String MultiSet Rewriting calculus
Authors: Bagossy Attila , Battyányi Péter 
Published: March 2024

AbstractIn this paper, we present an encoding of the $$\lambda $$
λ
-calculus in a multiset rewriting system and provide a few applications of the construction. For this purpose, we choose the calculus named String MultiSet Rewriting, which was introduced in Barbuti et al. (Electron Notes Theor Comput Sci 194:19–34, 2008) by Barbuti et al. With the help of our encoding, we give alternative proofs for the standardization and the finiteness of developments theorems in the $$\lambda $$
λ
-calculus.
Cardiac Rhabdomyomas Presenting with Critical Cardiac Obstruction in Neonates and Infants: Treatment Strategies and Outcome, A Single-Center Experience
Authors: Ng Li Yen , McGuinness Jonathan , Prendiville Terence , Franklin Orla , Walsh Mark , Kenny Damien , Nolke Lars , McMahon Colin J. 
Published: March 2024

AbstractCardiac rhabdomyomas are the most common benign pediatric heart tumor in infancy, which are commonly associated with tuberous sclerosis complex (TSC). Most rhabdomyomas are asymptomatic and spontaneously regress over time. However, some cases especially in neonates or small infants can present with hemodynamic instability. Surgical resection of the tumor, which has been the gold standard in alleviating obstruction, is not always possible and may be associated with significant morbidity and mortality. Recently, mammalian target of rapamycin inhibitors (mTORi) have been shown to be safe and effective in the treatment of TSC. We present the outcomes of neonates and an infant who received treatment for symptomatic rhabdomyomas at a tertiary cardiology center. Medical records were reviewed to obtain clinical, demographic, and outcome data. Six patients received interventions for symptomatic rhabdomyomas, median age at presentation was 1 day old (range from 1 to 121 days old), and 67% of the patients had a pathogenic mutation in TSC gene. One patient underwent surgical resection of solitary tumor at right ventricular outflow tract (RVOT) successfully. In the four patients with left ventricular outflow tract (LVOT) obstruction, two patients received combined therapy of surgical debulking of LVOT tumor, Stage I palliation procedure, and mTORi and two patients received mTORi therapy. One patient with RVOT obstruction underwent ductal stenting and received synergistic mTORi. Four of the five patients had good response to mTORi demonstrated by the rapid regression of rhabdomyoma size. 83% of patients are still alive at their latest follow-up, at two to eight years of age. One patient died on day 17 post-LVOT tumor resection and Hybrid stage one due to failure of hemostasis, in the background of familial factor VII deficiency. Treatment of symptomatic rhabdomyoma requires individualized treatment strategy based on the underlying pathophysiology, with involvement of multidisciplinary teams. mTORi is effective and safe in inducing rapid regression of rhabdomyomas. A standardized mTORi prescription and monitoring guide will ensure medication safety in neonates and infants with symptomatic cardiac rhabdomyoma. Although the majority of tumors responded to mTORi, some prove to be resistant. Further studies are warranted, ideally involving multiple international centers with a larger number of patients.
HLA class I NK-epitopes and KIR diversities in patients with multiple myeloma
Authors: Beelen Nicky A. , Molenbroeck Stefan J. J. , Groeneveld Lisette , Voorter Christien E. , Bos Gerard M. J. , Wieten Lotte 
Published: March 2024

AbstractMultiple myeloma (MM) is a hematological malignancy caused by the clonal expansion of malignant plasma cells in the bone marrow. Myeloma cells are susceptible to killing by natural killer (NK) cells, but NK cells fail to control disease progression, suggesting immunosuppression. The activation threshold of NK-effector function is regulated by interaction between KIRs and self-HLA class I, during a process called “education” to ensure self-tolerance. NK cells can respond to diseased cells based on the absence of HLA class I expression (“Missing-self” hypothesis). The HLA and KIR repertoire is extremely diverse; thus, the present study aimed to characterize potential variances in genotypic composition of HLA Class I NK-epitopes and KIRs between MM patients and healthy controls. Genotypic expression of KIR and HLA (HLA-C group-C1/C2 and Bw4 motifs (including HLA-A*23, A*24, A*32) were analyzed in 172 MM patients and 195 healthy controls. Compared to healthy controls, we did not observe specific KIR genes or genotypes, or HLA NK-epitopes with higher prevalence among MM patients. The presence of all three HLA NK-epitopes (C1+C2+Bw4+) was not associated with MM occurrence. However, MM patients were more likely to be C1-/C2+/Bw4+ (p = 0.049, OR 1.996). In line with this, there was a trend of increased genetic co-occurrence of Bw4 and KIR3DL1 in MM patients (p = 0.05, OR 1.557). Furthermore, MM patients were more likely to genetically express both C2/KIR2DL1 and Bw4/KIR3DL1 (p = 0.019, OR 2.453). Our results reveal an HLA NK-epitope combination that is associated with the occurrence of MM. No specific KIR genotypes were associated with MM.
Pharmacokinetics and pharmacodynamics of antibacterial peptide NZX in Staphylococcus aureus mastitis mouse model
Authors: Zheng Xueling , Yang Na , Mao Ruoyu , Hao Ya , Teng Da , Wang Jianhua 
Published: March 2024

Abstract
Staphylococcus aureus is associated with dairy mastitis, which causes serious economic losses to dairy farming industry. Antibacterial peptide NZX showed good antibacterial activity against S. aureus. This study aimed to evaluate pharmacokinetics and pharmacodynamics of NZX against S. aureus-induced mouse mastitis. NZX exhibited potent in vitro antibacterial activity against the test S. aureus strains (minimal inhibitory concentration (MIC): 0.23–0.46 μM), low mutant prevention concentration (MPC: 1.18–3.68 μM), and a long post antibiotic effect (PAE: 2.20–8.84 h), which was superior to those of lincomycin and ceftiofur. Antibacterial mechanisms showed that NZX could penetrate the cell membrane, resulting in obvious cell membrane perforation and morphological changes, and bind to intracellular DNA. Furthermore, NZX had a good stability in milk environment (retention rate: 85.36%, 24 h) than that in mammary homogenate (47.90%, 24 h). In mouse mastitis model, NZX (25–400 μg/gland) could significantly reduce the bacterial load of mammary tissue in a dose-dependent manner. In addition, NZX (100 μg/gland) could relieve the inflammatory symptoms of mammary tissue, and significantly decreased its pathological scores. The concentration–time curve of NZX (100 μg/gland) in the mammary tissue was plotted and the corresponding pharmacokinetic parameters were obtained by non-compartment model calculation. Those parameters of Tmax, T1/2, Cmax and AUC were 0.5 h, 35.11 h, 32.49 μg/g and 391 μg·h/g, respectively. Therefore, these results suggest that NZX could act as a promising candidate for treating dairy mastitis disease caused by S. aureus.

Key points
• NZX could kill S. aureus by dual mechanism involved in membrane and DNA disruption
• NZX could relieve S. aureus-induced mouse mastitis
• Pharmacokinetic parameters of NZX in mouse mammary gland were obtained
Automatic estimation of hallux valgus angle using deep neural network with axis-based annotation
Authors: Takeda Ryutaro , Mizuhara Hiroyasu , Uchio Akihiro , Iidaka Toshiko , Makabe Kenta , Kasai Taro , Omata Yasunori , Yoshimura Noriko , Tanaka Sakae , Matsumoto Takumi 
Published: March 2024

Abstract
Objectives
We developed the deep neural network (DNN) model to automatically measure hallux valgus angle (HVA) and intermetatarsal angle (IMA) on foot radiographs. The objective is to assess the accuracy of the model by comparing to the manual measurement of foot and ankle surgeons.

Materials and methods
A DNN was developed to predict the bone axes of the first proximal phalanx and all metatarsals from the first to the fifth in foot radiographs. The dataset used for model development consisted of 1798 radiographs collected from a population-based cohort and patients at our foot and ankle clinic. The retrospective validation cohort comprised of 92 radiographs obtained from 92 consecutive patients visiting our foot and ankle clinic. The mean absolute error (MAE) between automatic measurements by the model and the median of manual measurements by three foot and ankle surgeons was compared to 3° using one-tailed t-test and was also compared to the inter-rater difference in manual measurements among the three surgeons using two-tailed paired t-test.

Results
The MAE for HVA was 1.3° (upper limit of 95% CI 1.6°), and this was significantly smaller than the inter-rater difference of 2.0 ± 0.2° among the surgeons, demonstrating the superior accuracy of the model. In contrast, the MAE for IMA was 0.8° (upper limit of 95% CI 1.0°) that showed no significant difference from the inter-rater difference of 1.0 ± 0.1° among the surgeons.

Conclusion
Our model demonstrated the ability to measure the HVA and IMA with an accuracy comparable to that of specialists.
Neuropathy of the suprascapular and axillary nerves in rotator cuff arthropathy: a prospective electrodiagnostic study
Authors: Lopiz Yaiza , Rodríguez-González Alberto , Martín-Albarrán Susana , Herzog Raul , García-Fernández Carlos , Marco Fernando 
Published: March 2024

Abstract
Purpose
Prevalence of axillary (AN) and/or suprascapular (SSN) neuropathy in rotator cuff tear arthropathy (RCTA) is unknown. We aimed to prospectively evaluate for preoperative neurodiagnostic abnormalities in order to determine their prevalence, location, and influence on reverse shoulder arthroplasty (RSA) outcomes.

Methods
Patients who underwent RSA for RCTA were prospectively included. An electromyography and nerve conduction study were performed pre and post-surgery. Clinical situation: VAS, Relative Constant-Murley Score (rCMS) and ROM over a minimum of two years follow-up.

Results
Forty patients met the inclusion criteria; mean follow-up was 28.4 months (SD 4.4). Injuries in RCTA were present in 83.9% (77.4% in AN and 45.2% in SSN). There were no differences on preoperative VAS, ROM, and rCMS between patients with and without preoperative nerve injuries. Four acute postoperative neurological injuries were registered under chronic preoperative injuries. Six months after RSA, 69% of preoperative neuropathies had improved (82.14% chronic injuries and 77.7% disuse injuries). No differences in improvement between disuse and chronic injuries were found, but patients with preoperative neuropathy that had not improved at the postoperative electromyographic study at six months, scored worse on the VAS (1.44 vs 2.66; p .14) and rCMS (91.6 vs 89.04; p .27).

Conclusions
The frequency of axillary and suprascapular neuropathies in RCTA is much higher than expected. Most of these injuries improve after surgery, with almost complete neurophysiological recovery and little functional impact on RSA. However, those patients with preoperative neuropathies and absence of neurophysiological improvement six months after surgery have lower functional results.
Risk factors of early disease progression and decreased survival for multiple myeloma patients after upfront autologous stem cell transplantation
Authors: Hsu Te-Lin , Tsai Chun-Kuang , Liu Chun-Yu , Yeh Chiu-Mei , Lin Fen-Lan , Hsiao Liang-Tsai , Liu Yao-Chung , Chien Sheng-Hsuan , Wang Hao-Yuan , Ko Po-Shen , Lin Ting-An , Chen Wen-Chun , Chen Po-Min , Liu Jin-Hwang , Gau Jyh-Pyng , Liu Chia-Jen 
Published: March 2024

AbstractMultiple myeloma (MM) stands as the second most prevalent hematological malignancy, constituting approximately 10% of all hematological malignancies. Current guidelines recommend upfront autologous stem cell transplantation (ASCT) for transplant-eligible MM patients. This study seeks to delineate factors influencing post–ASCT outcomes in MM patients. Our cohort comprised 150 MM patients from Taipei Veterans General Hospital, with progression-free survival (PFS) as the primary endpoint and overall survival (OS) as the secondary endpoint. A Cox proportional hazards model was employed to discern potential predictive factors for survival. ASCT age ≥ 65 (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.08–3.47) and the presence of extramedullary disease (HR 2.53, 95% CI 1.53–4.19) negatively impacted PFS. Conversely, treatment response ≥ VGPR before ASCT (HR 0.52, 95% CI 0.31–0.87) and total CD34+ cells collected ≥ 4 × 106 cells/kg on the first stem cell harvesting (HR 0.52, 95% CI 0.32–0.87) were positively associated with PFS. For OS, patients with ISS stage III (HR 2.06, 95% CI 1.05–4.04), the presence of extramedullary disease (HR 3.92, 95% CI 2.03–7.58), light chain ratio ≥ 100 before ASCT (HR 7.08, 95% CI 1.45–34.59), post–ASCT cytomegalovirus infection (HR 9.43, 95% CI 3.09–28.84), and a lower conditioning melphalan dose (< 140 mg/m2; HR 2.75, 95% CI 1.23–6.17) experienced shorter OS. In contrast, post–ASCT day + 15 absolute monocyte counts (D15 AMC) > 500/µl (HR 0.36, 95% CI 0.17–0.79) and post–ASCT day + 15 platelet counts (D15 PLT) > 80,000/µl (HR 0.48, 95% CI 0.24–0.94) were correlated with improved OS. Significantly, early PLT and AMC recovery on day + 15 predicting longer OS represents a novel finding not previously reported. Other factors also align with previous studies. Our study provides real-world insights for post–ASCT outcome prediction beyond clinical trials.
Ruxolitinib Adherence in Myelofibrosis and Polycythemia Vera: the “RAMP” Italian multicenter prospective study
Authors: Palandri F. , Auteri G. , Abruzzese E. , Caocci G. , Bonifacio M. , Mendicino F. , Latagliata R. , Iurlo A. , Branzanti F. , Garibaldi B. , Trawinska M. M. , Cattaneo D. , Krampera M. , Mulas O. , Martino E. A. , Cavo M. , Vianelli N. , Impera S. , Efficace F. , Heidel F. , Breccia M. , Elli E. M. , Palumbo G. A. 
Published: March 2024

AbstractRuxolitinib is beneficial in patients with myelofibrosis (MF) and polycythemia vera (PV). Information on ruxolitinib adherence is scant. The Ruxolitinib Adherence in Myelofibrosis and Polycythemia Vera (RAMP) prospective multicenter study (NCT06078319) included 189 ruxolitinib-treated patients. Patients completed the Adherence to Refills and Medications Scale (ARMS) and Distress Thermometer and Problem List (DTPL) at the earliest convenience, after registration in the study, and at later timepoints. At week-0, low adherence (ARMS > 14) and high distress (DT ≥ 4) were declared by 49.7% and 40.2% of patients, respectively. The main reason for low adherence was difficult ruxolitinib supply (49%), intentional (4.3%) and unintentional (46.7%) non-take. In multivariable regression analysis, low adherence was associated to male sex (p = 0.001), high distress (p < 0.001), and treatment duration ≥ 1 year (p = 0.03). Over time, rates of low adherence and high distress remained stable, but unintentional non-take decreased from 47.9% to 26.0% at week-48. MF patients with stable high adherence/low distress were more likely to obtain/maintain the spleen response at week-24. Low adherence to ruxolitinib represents an unmet clinical need that require a multifaceted approach, based on reason behind it (patients characteristics and treatment duration). Its recognition may help distinguishing patients who are truly refractory and those in need of therapy optimization.
Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)
Authors: Huang Xiao , Bao Huihui , Ding Congcong , Li Junpei , Cao Tianyu , Liu Lishun , Wei Yaping , Zhou Ziyi , Zhang Nan , Song Yun , Chen Ping , Jiang Chongfei , Xie Liling , Qin Xianhui , Zhang Yan , Li Jianping , Sun Ningling , Tang Genfu , Wang Xiaobin , Wang Hong , Huo Yong , Cheng Xiaoshu ,   for the Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy) Trial Investigators
Published: March 2024

Abstract
Background
While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes.

Methods
This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment.

Results
The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0–1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2–1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering.

Conclusions
This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg.

ClinicalTrials.gov Identifier
NCT03472508 (Registration Date: March 21, 2018).
MSUT2 regulates tau spreading via adenosinergic signaling mediated ASAP1 pathway in neurons
Authors: Xu Hong , Qiu Qi , Hu Peng , Hoxha Kevt’her , Jang Elliot , O’Reilly Mia , Kim Christopher , He Zhuohao , Marotta Nicholas , Changolkar Lakshmi , Zhang Bin , Wu Hao , Schellenberg Gerard D. , Kraemer Brian , Luk Kelvin C. , Lee Edward B. , Trojanowski John Q. , Brunden Kurt R. , Lee Virginia M.-Y. 
Published: March 2024

AbstractInclusions comprised of microtubule-associated protein tau (tau) are implicated in a group of neurodegenerative diseases, collectively known as tauopathies, that include Alzheimer’s disease (AD). The spreading of misfolded tau “seeds” along neuronal networks is thought to play a crucial role in the progression of tau pathology. Consequently, restricting the release or uptake of tau seeds may inhibit the spread of tau pathology and potentially halt the advancement of the disease. Previous studies have demonstrated that the Mammalian Suppressor of Tauopathy 2 (MSUT2), an RNA binding protein, modulates tau pathogenesis in a transgenic mouse model. In this study, we investigated the impact of MSUT2 on tau pathogenesis using tau seeding models. Our findings indicate that the loss of MSUT2 mitigates human tau seed-induced pathology in neuron cultures and mouse models. In addition, MSUT2 regulates many gene transcripts, including the Adenosine Receptor 1 (A1AR), and we show that down regulation or inhibition of A1AR modulates the activity of the “ArfGAP with SH3 Domain, Ankyrin Repeat, and PH Domain 1 protein” (ASAP1), thereby influencing the internalization of pathogenic tau seeds into neurons resulting in reduction of tau pathology.
Survival and hormone production of isolated mouse follicles in three-dimensional artificial scaffolds after stimulation with bpV(HOpic)
Authors: Keckstein Philip , Dittrich Ralf , Bleisinger Nathalie , Hoffmann Inge , Beckmann Matthias W. , Gebhardt Albrecht , Schmid Benjamin , Keckstein Simon 
Published: March 2024

Abstract
Purpose
To preserve fertility before gonadotoxic therapy, ovarian tissue can be removed, cryopreserved, and transplanted back again after treatment. An alternative is the artificial ovary, in which the ovarian follicles are extracted from the tissue, which reduces the risk of reimplantation of potentially remaining malignant cells. The PTEN inhibitor bpV(HOpic) has been shown to activate human, bovine and alpacas ovarian follicles, and it is therefore considered a promising substance for developing the artificial ovary. The purpose of this study was to examine the impact of different scaffolds and the vanadate derivative bpV(HOpic) on mice follicle survival and hormone secretion over 10 days.

Methods
A comparative analysis was performed, studying the survival rates (SR) of isolated mice follicle in four different groups that differed either in the scaffold (polycaprolactone scaffold versus polyethylene terephthalate membrane) or in the medium—bpV(HOpic) versus control medium. The observation period of the follicles was 10 days. On days 2, 6, and 10, the viability and morphology of the follicles were checked using fluorescence or confocal microscopy. Furthermore, hormone levels of estrogen (pmol/L) and progesterone (nmol/L) were determined.

Results
When comparing the SR of follicles among the four groups, it was observed that on day 6, the study groups utilizing the polycaprolactone scaffold with bpV(HOpic) in the medium (SR: 0.48 ± 0.18; p = 0.004) or functionalized in the scaffold (SR: 0.50 ± 0.20; p = 0.003) exhibited significantly higher survival rates compared to the group using only the polyethylene terephthalate membrane (SR: 0). On day 10, a significantly higher survival rate was only noted when comparing the polycaprolactone scaffold with bpV(HOpic) in the medium to the polyethylene terephthalate membrane group (SR: 0.38 ± 0.20 versus 0; p = 0.007). Higher levels of progesterone were only significantly associated with better survival rates in the group with the polycaprolactone scaffold functionalized with bpV(HOpic) (p = 0.017).

Conclusion
This study demonstrates that three-dimensional polycaprolactone scaffolds improve the survival rates of isolated mice follicles in comparison with a conventional polyethylene terephthalate membrane. The survival rates slightly improve with added bpV(HOpic). Furthermore, higher rates of progesterone were also partly associated with improved survival.