bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of myocardial perfusion scintigraphy in asymptomatic patients with diabetes mellitus at high cardiovascular risk: 5-year follow-up of the prospective multicenter BARDOT trial
Authors: Caobelli Federico , Haaf Philip , Haenny Gianluca , Pfisterer Matthias , Zellweger Michael J. ,   on behalf of the BARDOT Investigators
Published: April 2021

Abstract
Background
The Basel Asymptomatic High-Risk Diabetics’ Outcome Trial (BARDOT) demonstrated that asymptomatic diabetic patients with an abnormal myocardial perfusion scintigraphy (MPS) were at increased risk of major adverse cardiovascular events (MACEs) at 2-year follow-up. It remains unclear whether this finding holds true even for a longer follow-up.

Methods
Four hundred patients with type 2 diabetes, neither history nor symptoms of coronary artery disease (CAD), were evaluated clinically and with MPS. Patients were followed up for 5 years. Major adverse cardiovascular events (MACEs) were defined as all-cause death, myocardial infarction, or late coronary revascularization.

Results
At baseline, an abnormal MPS (SSS ≥ 4 or SDS ≥ 2) was found in 87 of 400 patients (22%). MACE within 5 years occurred in 14 patients with abnormal MPS (16.1%) and in 22 with normal scan (1.7%), p = 0.009; 15 deaths were recorded. Patients with completely normal MPS (SSS and SDS = 0) had lower rates of MACEs than patients with abnormal scans (2.5% vs. 7.0%, p = 0.032). Patients with abnormal MPS who had undergone revascularization had a lower mortality rate and a better event-free survival from MI and revascularization than patients with abnormal MPS who had either undergone medical therapy only or could not be revascularized (p = 0.002).

Conclusions
MPS may have prognostic value in asymptomatic diabetic patients at high cardiovascular risk over a follow-up period of 5 years. Patients with completely normal MPS have a low event rate and may not need retesting within 5 years. Patients with an abnormal MPS have higher event rates and may benefit from a combined medical and revascularization approach.
The development and maintenance of sex differences in dietary breadth and complexity in Bornean orangutans
Authors: Schuppli Caroline , Atmoko S. Suci Utami , Vogel Erin R. , van Schaik Carel P. , van Noordwijk Maria A. 
Published: April 2021

Abstract
Orangutans show a pronounced sexual dimorphism, with flanged males (i.e., males with fully grown secondary sexual characteristics) reaching twice the size of adult females. Furthermore, adult orangutans show sex-specific dispersal and activity patterns. This study investigates sex differences in adult foraging behavior and sheds light on how these differences develop in immatures. We analyzed 11 years of feeding data on ten adult female, seven flanged male, and 14 immature Bornean orangutans (Pongo pygmaeus wurmbii) at Tuanan in Central Kalimantan, Indonesia. We found that the diets of the adult females were significantly broader and required more processing steps before ingestion than the diets of flanged males. We also found evidence for a similar difference in overall diet repertoire sizes. For the immatures, we found that whereas females reached 100% of their mothers’ diet spectrum size by the age of weaning, males reached only around 80%. From the age of 4 years on (i.e., years before being weaned) females had significantly broader daily diets than males. We found no difference in daily or overall diet processing intensity of immature males and females but found preliminary evidence that immature males included fewer items of their mother’s diet in their own diets that were processing-intensive. Overall, our results suggest that by eating a broader variety and more complex to process food items, female orangutans go to greater lengths to achieve a balanced diet than males do. These behavioral differences are not just apparent in adult foraging behavior but also reflected in immature development from an early age on.

Significance Statement
In many species, males and females have different nutritional needs and are thus expected to show sex-specific foraging behavior. Sex differences in several aspects of foraging behavior have been found in various species, but it remains largely unclear when and how those develop during ontogeny, which is especially relevant for long-lived altricial species that learn foraging skills over many years. In our study, we analyzed a cross-sectional and longitudinal data set containing more than 750,000 feeding events of adult and immature Bornean orangutans (Pongo pygmaeus wurmbii). We found that adult females had significantly broader and more complex diets than males. We also found that these differences started to develop during infancy, suggesting that immature orangutans prepare for their sex-specific foraging niches long before those become physiologically relevant while they are still in constant association with their mothers and before being frequently exposed to other role models.
Laparoscopic Versus Open Liver Resection for Hepatocellular Carcinoma: A Case Controlled Study with Propensity Score Matching
Authors: Uemoto Yusuke , Taura Kojiro , Nishio Takahiro , Kimura Yusuke , Nam Nguyen Hai , Yoshino Kenji , Yoh Tomoaki , Koyama Yukinori , Ogiso Satoshi , Fukumitsu Ken , Ishii Takamichi , Seo Satoru , Uemoto Shinji 
Published: April 2021

AbstractBackgroundSeveral studies have suggested that laparoscopic liver resection (LLR) is associated with fewer postoperative complications than open liver resection (OLR) for hepatocellular carcinoma (HCC). However, this issue remains controversial since the data may have been attributable to an imbalance in patients’ background.MethodsWe retrospectively analyzed 290 hepatectomies for HCC undertaken between 2011 and 2019. Liver resection difficulty was based on the 3 levels of the Institut Mutualiste Montsouris classification. Resection ratio was calculated using computed tomography volumetry. Patient characteristics were compared between the LLR and OLR groups. Propensity score matching (PSM) was adopted to adjust the imbalance between the cohorts, and the incidence of postoperative complications was compared.ResultsThe difficulty and resection ratio were significantly lower in LLR (n = 112) than in OLR (n = 178) (difficulty grade I/II/III: 84/10/18 vs. 43/39/96, p < 0.001; resection ratio: 11.4 ± 12.7 vs. 22.7 ± 17.2%, p < 0.001). The incidence of postoperative complications (Clavien–Dindo grade III or more) was lower in LLR (2.7% vs. 21.9%, p < 0.001), which was mainly attributable to fewer incidences of ascites and pleural effusion. PSM generated 68 well‐matched patients in each group. The lower incidence of postoperative complications in LLR was also maintained in the PSM cohort (2.9% vs. 16.2%, p = 0.017). On multivariate analysis, LLR was the independent predictor of postoperative complications (OR 0.184, 95% CI 0.051–0.672, p = 0.010).ConclusionThe present study demonstrated that a laparoscopic approach reduces the incidence of postoperative complications in liver resection for HCC.
Survival and treatment patterns of patients with relapsed or refractory multiple myeloma in France — a cohort study using the French National Healthcare database (SNDS)
Authors: Touzeau Cyrille , Quignot Nadia , Meng Jie , Jiang Heng , Khachatryan Artak , Singh Moushmi , Taieb Vanessa , Chauny Jean-Vannak , Désaméricq Gaëlle 
Published: April 2021

AbstractOver the past decade, several drugs have been approved for the treatment of relapsed or refractory multiple myeloma (RRMM). This retrospective study, using the French National Healthcare database (SNDS), describes the treatment patterns and outcomes of patients with RRMM treated in real-world clinical practice in France. Patients were adults, with a diagnosis of multiple myeloma, who initiated second-line (2L) treatment approved for use in France between 2014 and 2018; this included bortezomib, carfilzomib, daratumumab, ixazomib, lenalidomide, or pomalidomide. Data were analyzed overall, by first-line (1L) autologous stem cell transplant (ASCT) status and by lenalidomide treatment status at 2L. In total, 12987 patients with RRMM were included in the study (mean age 69.5 years); 27% received an ASCT at 1L, and 30% received a lenalidomide-sparing regimen at 2L. Overall, and among the ASCT and non-ASCT subgroups, most patients received a bortezomib-based regimen at 1L, whereas lenalidomide-based regimens were most common at 2L. Among patients who received a lenalidomide-sparing regimen at 2L, this was most often a proteasome inhibitor-based regimen. Mortality rate was 26.1/100 person-years, and median (95% confidence interval) survival from 2L initiation was 32.4 (31.2–33.6) months. Survival differed by various factors, shorter survival was reported in the non-ASCT group, those receiving a lenalidomide-sparing regimen at 2L, older patients (≥ 70 years), and those with multiple comorbidities. This analysis provides insight into the real-world use of approved novel MM treatments and highlights an ongoing unmet need to improve outcomes, particularly for selected patient groups.
Cartilaginous bending spring for preventing tympanic membrane graft medialisation in anterior or subtotal tympanic membrane perforations—how I do it
Authors: Mantsopoulos Konstantinos , Iro Heinrich , Hornung Joachim 
Published: April 2021

Abstract
Background
The reconstruction of anterior or subtotal tympanic membrane perforations is critical due to the risk of anterior graft medialisation and retraction or recurrent perforation.

Method
After reconstruction of the tympanic membrane by means of grafting, a rectangular cartilage strut (length 6 mm, breadth 2 mm, thickness 0.1 mm) is prepared using a cartilage knife and scalpel. This strut graft is placed between the cartilage graft and the promontory in the anterior inferior part of the middle ear cavity.

Conclusion
Our experience shows that using a U-shaped cartilage strut to sustain the tympanic reconstruction effectively prevents the medialisation of the graft and recurrent perforations.
FMRI-based prediction of naltrexone response in alcohol use disorder: a replication study
Authors: Bach Patrick , Weil Georg , Pompili Enrico , Hoffmann Sabine , Hermann Derik , Vollstädt-Klein Sabine , Kiefer Falk , Mann Karl , Sommer Wolfgang H. 
Published: April 2021

AbstractPharmacological treatment in alcohol use disorder suffers from modest effect sizes. Efforts have been undertaken to identify patient characteristics that help to select individuals that benefit from pharmacological treatment. Previous studies indicated that neural alcohol cue-reactivity (CR) might provide a marker that identifies patients, which benefit from naltrexone treatment.We investigated the reproducibility of the association between ventral striatum (VS) activation and naltrexone (NTX) treatment response by analyzing data from a recent longitudinal clinical trial inN = 44 abstinent treatment-seeking alcohol-dependent patients. A follow-up was conducted over 3 months. We computed the percentage of significant voxels in VS and tested main effects and interactions with NTX treatment on relapse risk using Cox Regression models.We found a significant interaction effect between pre-treatment cue reactivity in the VS and NTX treatment on time to first heavy relapse (Hazard Ratio = 7.406, 95% CI 1.17–46.56,p = 0.033), such that the patient group with high VS activation (defined by a mean split) showed a significant medication effect (Hazard Ratio = 0.140, 95% CI 0.02–0.75,p = 0.022) with a number needed to treat of 3.4 [95% CI 2.413.5], while there was no significant effect in the group with low VS activation (Hazard Ratio = 0.726,p = 0.454).Thus, using an independent sample we replicated the previously described positive association between VS activation and NTX efficacy. Although our results should be considered cautiously in light of the small sample size, our results support the potential of neural alcohol CR as a tool for precision medicine approaches in alcohol dependence.
RFC1 AAGGG repeat expansion masquerading as Chronic Idiopathic Axonal Polyneuropathy
Authors: Tagliapietra Matteo , Cardellini Davide , Ferrarini Moreno , Testi Silvia , Ferrari Sergio , Monaco Salvatore , Cavallaro Tiziana , Fabrizi Gian Maria 
Published: April 2021

Abstract
Background
A biallelic intronic AAGGG repeat expansion in the Replication Factor C subunit 1 (RFC1) gene has been recently associated with Cerebellar Ataxia, Neuropathy, Vestibular Areflexia Syndrome, a disorder often presenting as a slowly evolving sensory neuropathy at the onset. “Chronic Idiopathic Axonal Polyneuropathy” (CIAP) is a common indolent axonal neuropathy of adulthood which remains without an identifiable cause despite thorough investigations.

Methods
We screened 234 probands diagnosed with CIAP for a pathogenic biallelic RFC1 AAGGG repeat expansion. Patients were selected from 594 consecutive patients with neuropathy referred to our tertiary-care center for a sural nerve biopsy over 10 years.

Results
The RFC1 AAGGG repeat expansion was common in patients with pure sensory neuropathy (21/40, 53%) and less frequent in cases with predominantly sensory (10/56, 18%, P < 0.001) or sensorimotor (3/138, 2%, P < 0.001) neuropathy. The mutation was associated with sensory ataxia (τb = 0.254, P < 0.001), autonomic disturbances (35% vs 8%, Prevalence Odds Ratio—POR 6.73 CI 95% 2.79–16.2, P < 0.001), retained deep tendon reflexes (score 18.0/24 vs 11.5/24, R = 0.275, P < 0.001). On pathology, we observed absent/scant regenerative changes (τb = − 0.362, P < 0.001), concomitant involvement of large (100% and 99%, n.s.), small myelinated (97% vs 81%, POR 7.74 CI 95% 1.03–58.4, P = 0.02) and unmyelinated nerve fibers (85% vs 41%, POR 8.52 CI 95% 3.17–22.9, P < 0.001). Cerebellar or vestibular involvement was similarly rare in the two groups.

Conclusions
This study highlights the frequent occurrence of the RFC1 AAGGG repeat expansion in patients diagnosed with CIAP and characterizes the clinical and pathological features of the related neuro(no)pathy.
Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer
Authors: Rachner Tilman D. , Kasimir-Bauer Sabine , Goebel Andy , Erdmann Kati , Hoffmann Oliver , Rauner Martina , Hofbauer Lorenz C. , Kimmig Rainer , Bittner Ann-Kathrin 
Published: April 2021

Abstract
Background
Neuropilin-1 (NRP-1) is a transmembrane protein that acts as a multifunctional non-tyrosine kinase receptor with an established role in development and immunity. NRP-1 also regulates tumor biology, and high expression levels of tissue NRP-1 have been associated with a poor prognosis. Recently, ELISA-based quantification of soluble NRP-1 (sNRP-1) has become available, but little is known about the prognostic value of sNRP-1 in malignancies.

Materials and methods
We measured sNRP-1 in the serum of 509 patients with primary early breast cancer (BC) at the time of diagnosis using ELISA.

Results
Mean serum values of sNRP-1 were 1.88 ± 0.52 nmol/l (= 130.83 ± 36.24 ng/ml). SNRP-1 levels weakly correlated with age, and were higher in peri- and postmenopausal patients compared to premenopausal patients, respectively (p < 0.0001). Low levels of sNRP-1 were associated with a significant survival benefit compared to high sNRP-1 levels at baseline (p = 0.005; HR 1.94; 95%CI 1.23–3.06). These findings remained significant after adjustment for tumor stage including lymph node involvement, grading, hormone receptor, HER2 status, and age (p = 0.022; HR 1.78; 95%CI 1.09–2.91).

Conclusion
Our findings warrant further investigations into the prognostic and therapeutic potential of sNRP-1 in BC.
Endoscopic cardial constriction with band ligation in the treatment of refractory gastroesophageal reflux disease: a preliminary feasibility study
Authors: Li Zhi-Tong , Ji Feng , Han Xin-Wei , Zhang Rui , Chen Li-Dong , Li Chun-Xia , Yuan Li-Li , Wang Zhong-Gao , Liu Kang-Dong 
Published: April 2021

Abstract
Background
Gastroesophageal reflux disease (GERD) is a common digestive disease, could cause extra-esophageal symptoms. Peroral endoscopic cardial constriction with band ligation (PECC-b) is a minimally invasive method for the treatment of GERD in recent years. The goals of this study were to evaluate the clinical efficacy of PECC-b to treat gastroesophageal reflux-related symptoms.

Methods
A retrospective study of patients undergoing PECC-b between January 2017 and December 2018 at a single institution was conducted. All patients confirmed GERD by endoscopy, esophageal PH-impedance monitoring, esophageal manometry and symptom questionnaires. The outcome measures included reflux-related scores, patients’ satisfaction and drug independence after 12 months following surgery.

Results
A total of 68 patients, with follow-up of 12 months post surgery, were included in the final analysis. The symptom scores were all significantly decreased as compared with preoperation (P < 0.05). The esophageal symptom scores showed a better improvement than extra-esophageal symptoms (P < 0.001). Fifty-three (77.9%) patients achieved complete drug therapy independence and 52 (76.5%) patients were completely or partially satisfied with the symptom relief following surgery.

Conclusions
The PECC-b is a safe, effective and recommended approach for the control of GERD-related symptoms. Further multicenter prospective studies are required to confirm these outcomes.
Oral health–related quality of life of patients with oral chronic graft-versus-host disease
Authors: Stolze Juliette , Boor Marlou , Hazenberg Mette D. , Brand Henk S. , Raber-Durlacher Judith E. , Laheij Alexa M. G. A. 
Published: April 2021

Abstract
Purpose
Symptoms of oral chronic graft-versus-host-disease (cGVHD) may significantly affect the oral health–related quality of life (OHRQoL). This study aimed to assess the OHRQoL in patients with oral cGVHD and to examine whether oral cGVHD symptoms, mucosal cGVHD, and salivary gland function correlated with OHRQoL.

Methods
Patients referred to the oral cGVHD outpatient clinic were included. Severity of oral mucosal cGVHD, oral cGVHD symptoms, and OHRQoL was assessed by the NIH OMS, NIH OSS, and OHIP-14, respectively. Unstimulated and stimulated whole salivary flow rates were determined and categorized into “hyposalivation,” “normal salivary flow,” and “hypersalivation.”

Results
Of 56 included patients, 80% had mild, moderate, or severe oral mucosal cGVHD. Mean total score of OHRQoL was 16.5 (±11.7), negatively affected by functional problems. Patients reported highest scores regarding oral sensitivity and xerostomia. Significant correlations were found between severity of oral pain and OHRQoL and between oral sensitivity and OHRQoL. No correlation was found between oral mucosal cGVHD and OHRQoL. Patients with hyposalivation, normal salivary flow, and hypersalivation reported equal levels of OHRQoL.

Conclusion
Results demonstrate that the OHRQoL was mostly negatively affected by complaints of oral pain and oral sensitivity and less by the severity of oral mucosal cGVHD assessed by the NIH OMS score. Special attention of (oral) health care professionals for patients with oral cGVHD is mandatory to alleviate their symptoms and improve OHRQoL.
Lights Out on graphs
Authors: Berman Abraham , Borer Franziska , Hungerbühler Norbert 
Published: April 2021

AbstractWe model the Lights Out game on general simple graphs in the framework of linear algebra over the field $$\mathbb{F}_{2}$$

F
2

. Based upon a version of the Fredholm alternative, we introduce a separating invariant of the game, i.e., an initial state can be transformed into a final state if and only if the values of the invariant of both states agree. We also investigate certain states with particularly interesting properties. Apart from the classical version of the game, we propose several variants, in particular a version with more than only two states (light on, light off), where the analysis relies on systems of linear equations over the ring $$\mathbb{Z}_{n}$$

Z
n

. Although it is easy to find a concrete solution of the Lights Out problem, we show that it is NP-hard to find a minimal solution. We also propose electric circuit diagrams to actually realize the Lights Out game.
One-step CZT electroplating from alkaline solution on flexible Mo foil for CZTS absorber
Authors: Marchi C. , Panzeri G. , Pedrazzetti L. , Khalil M. I. , Lucotti A. , Parravicini J. , Acciarri M. , Binetti S. , Magagnin L. 
Published: April 2021

AbstractIn this work, Cu-Zn-Sn (CZT) is co-electrodeposited onto a flexible Mo substrate exploiting an alkaline bath (pH 10). The plating solution is studied by cyclic voltammetry, highlighting the effects of potassium pyrophosphate (K4P2O7) and EDTA-Na2 on the electrochemical behavior and stability of the metallic ionic species. The optimized synthesis results in a homogeneous precursor layer, with composition Cu 44 ± 2 at. %, Zn 28 ± 1 at. %, and Sn 28 ± 2 at. %. Soft and reactive annealing are employed respectively to promote intermetallic phase formation and sulfurization of the precursor to obtain CZTS. Microstructural (XRD, Raman), morphological (SEM), and compositional (EDX, XRF) characterization is carried out on CZT and CZTS films, showing a minor presence of secondary phases. Finally, photo-assisted water splitting tests are performed considering a CZTS/CdS/Pt photoelectrode, showing a photocurrent density of 1.01 mA cm−2 at 0 V vs. RHE under 1 sun illumination.
Graphical abstract
Pyrrolizidine alkaloids cause cell cycle and DNA damage repair defects as analyzed by transcriptomics in cytochrome P450 3A4-overexpressing HepG2 clone 9 cells
Authors: Abdelfatah Sara , Naß Janine , Knorz Caroline , Klauck Sabine M. , Küpper Jan-Heiner , Efferth Thomas 
Published: April 2021

AbstractPyrrolizidine alkaloids (PAs) are a large group of highly toxic chemical compounds, which are found as cross-contaminants in numerous food products (e.g., honey), dietary supplements, herbal teas, and pharmaceutical herbal medicines. PA contaminations are responsible for serious hepatotoxicity and hepatocarcinogenesis. Health authorities have to set legal limit values to guarantee the safe consumption of plant-based nutritional and medical products without harmful health. Toxicological and chemical analytical methods are conventionally applied to determine legally permitted limit values for PAs. In the present investigation, we applied a highly sensitive transcriptomic approach to investigate the effect of low concentrations of five PAs (lasiocarpine, riddelliine, lycopsamine, echimidine, and monocrotaline) on human cytochrome P450 3A4-overexpressing HepG2 clone 9 hepatocytes. The transcriptomic profiling of deregulated gene expression indicated that the PAs disrupted important signaling pathways related to cell cycle regulation and DNA damage repair in the transfected hepatocytes, which may explain the carcinogenic PA effects. As PAs affected the expression of genes that involved in cell cycle regulation, we applied flow cytometric cell cycle analyses to verify the transcriptomic data. Interestingly, PA treatment led to an arrest in the S phase of the cell cycle, and this effect was more pronounced with more toxic PAs (i.e., lasiocarpine and riddelliine) than with the less toxic monocrotaline. Using immunofluorescence, high fractions of cells were detected with chromosome congression defects upon PA treatment, indicating mitotic failure. In conclusion, the tested PAs revealed threshold concentrations, above which crucial signaling pathways were deregulated resulting in cell damage and carcinogenesis. Cell cycle arrest and DNA damage repair point to the mutagenicity of PAs. The disturbance of chromosome congression is a novel mechanism of Pas, which may also contribute to PA-mediated carcinogenesis. Transcriptomic, cell cycle, and immunofluorescence analyses should supplement the standard techniques in toxicology to unravel the biological effects of PA exposure in liver cells as the primary target during metabolization of PAs.Graphical abstract