bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genus zero Gopakumar-Vafa invariants from open strings
Authors: Collinucci Andrés , Sangiovanni Andrea , Valandro Roberto 
Published: September 2021

Abstract
We propose a new way to compute the genus zero Gopakumar-Vafa invariants for two families of non-toric non-compact Calabi-Yau threefolds that admit simple flops: Reid’s Pagodas, and Laufer’s examples. We exploit the duality between M-theory on these threefolds, and IIA string theory with D6-branes and O6-planes. From this perspective, the GV invariants are detected as five-dimensional open string zero modes. We propose a definition for genus zero GV invariants for threefolds that do not admit small crepant resolutions. We find that in most cases, non-geometric T-brane data is required in order to fully specify the invariants.
Innovative radiation oncology Together – Precise, Personalized, Human
Authors: Krug David , Hecht Markus , Ebert Nadja , Mäurer Matthias , Fleischmann Daniel F. , Fokas Emmanouil , Straube Christoph , Nicolay Nils Henrik , Hörner-Rieber Juliane , Schmitt Daniela , von Neubeck Cläre , Zamboglou Constantinos , Sperk Elena , Kaul David , Hess Julia , Corradini Stefanie , Seidel Clemens , Gani Cihan , Baues Christian , Frey Benjamin , Blanck Oliver , Gauer Tobias , Niyazi Maximilian 
Published: September 2021

Abstract
Purpose
Scientific and clinical achievements in radiation, medical, and surgical oncology are changing the landscape of interdisciplinary oncology. The German Society for Radiation Oncology (DEGRO) working group of young clinicians and scientists (yDEGRO) and the DEGRO representation of associate and full professors (AKRO) are aware of the essential role of radiation oncology in multidisciplinary treatment approaches. Together, yDEGRO and AKRO endorsed developing a German radiotherapy & radiation oncology vision 2030 to address future challenges in patient care, research, and education. The vision 2030 aims to identify priorities and goals for the next decade in the field of radiation oncology.

Methods
The vision development comprised three phases. During the first phase, areas of interest, objectives, and the process of vision development were defined jointly by the yDEGRO, AKRO, and the DEGRO board. In the second phase, a one-day strategy retreat was held to develop AKRO and yDEGRO representatives’ final vision from medicine, biology, and physics. The third phase was dedicated to vision interpretation and program development by yDEGRO representatives.

Results
The strategy retreat’s development process resulted in conception of the final vision “Innovative radiation oncology Together – Precise, Personalized, Human.” The first term “Innovative radiation oncology” comprises the promotion of preclinical research and clinical trials and highlights the development of a national committee for strategic development in radiation oncology research. The term “together” underpins collaborations within radiation oncology departments as well as with other partners in the clinical and scientific setting. “Precise” mainly covers technological precision in radiotherapy as well as targeted oncologic therapeutics. “Personalized” emphasizes biology-directed individualization of radiation treatment. Finally, “Human” underlines the patient-centered approach and points towards the need for individual longer-term career curricula for clinicians and researchers in the field.

Conclusion
The vision 2030 balances the ambition of physical, technological, and biological innovation as well as a comprehensive, patient-centered, and collaborative approach towards radiotherapy & radiation oncology in Germany.
Patterns of brain function associated with cannabis cue-reactivity in regular cannabis users: a systematic review of fMRI studies
Authors: Sehl Hannah , Terrett Gill , Greenwood Lisa-Marie , Kowalczyk Magdalena , Thomson Hannah , Poudel Govinda , Manning Victoria , Lorenzetti Valentina 
Published: September 2021

Abstract
Rationale
Regular cannabis use (i.e. ≥ monthly) is highly prevalent, with past year use being reported by ~ 200 million people globally.High reactivity to cannabis cues is a key feature of regular cannabis use and has been ascribed to greater cannabis exposure and craving, but the underlying neurobiology is yet to be systematically integrated.

Objectives
We aim to systematically summarise the findings from fMRI studies which examined brain function in cannabis users while exposed to cannabis vs neutral stimuli during a cue-reactivity fMRI task.

Methods
A systematic search of PsycINFO, PubMed and Scopus databases was pre-registered in PROSPERO (CRD42020171750) and conducted following PRISMA guidelines. Eighteen studies met inclusion/exclusion criteria. Samples comprised 918 participants (340 female) aged 16–38 years. Of these, 603 were regular cannabis users, and 315 were controls.

Results
The literature consistently reported greater brain activity in cannabis users while exposed to cannabis vs neutral stimuli in three key brain areas: the striatum, the prefrontal (anterior cingulate, middle frontal) and the parietal cortex (posterior cingulate/precuneus) and additional brain regions (hippocampus, amygdala, thalamus, occipital cortex). Preliminary correlations emerged between cannabis craving and the function of partially overlapping regions (amygdala, striatum, orbitofrontal cortex ).

Conclusions
Exposure to cannabis-cues may elicit greater brain function and thus trigger cravings in regular cannabis users and thus trigger cannabis craving. Standardised and longitudinal assessments of cannabis use and related problems are required to profile with greater precision the neurobiology of cannabis cue-reactivity, and its role in predicting cravings and relapse.
Eltrombopag treatment of patients with secondary immune thrombocytopenia: retrospective EHR analysis
Authors: Patwardhan Pallavi , Landsteiner Adrienne , Lal Lincy S. , Geevarghese Lincy , Le Lisa , Nandal Savita , Cuker Adam 
Published: September 2021

AbstractImmune thrombocytopenia (ITP) may occur in isolation (primary) or in association with a predisposing condition (secondary ITP [sITP]). Eltrombopag is a well-studied treatment for primary ITP, but evidence is scarce for sITP. We evaluated real-world use of eltrombopag for sITP using electronic health records. Eligible patients had diagnoses of ITP and a qualifying predisposing condition, and eltrombopag treatment. We described patient characteristics, treatment patterns, platelet counts, and thrombotic and bleeding events. We identified 242 eligible patients; the most common predisposing conditions were hepatitis C and systemic lupus erythematosus. Average duration of eltrombopag treatment was 6.1 months. Most (81.4%) patients achieved a platelet count ≥ 30,000/µL at a mean of 0.70 months, 70.2% reached ≥ 50,000/µL at a mean of 0.95 months, and 47.1% achieved a complete response of > 100,000/µL at a mean of 1.43 months after eltrombopag initiation. At eltrombopag discontinuation, 105 patients (43%) experienced a treatment-free period for a mean 3.3 months. Bleeding events occurred with similar frequency before and during eltrombopag treatment whereas thrombotic events were less frequent during eltrombopag treatment. Our results suggest similar rates of platelet response with eltrombopag in patients with sITP as compared with primary ITP. In addition, a treatment-free period is possible for a substantial minority of patients.
Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays
Authors: Ding James , Frantzeskos Antonios , Orozco Gisela 
Published: September 2021

AbstractGenetic studies, including genome-wide association studies, have identified many common variants that are associated with autoimmune diseases. Strikingly, in addition to being frequently observed in healthy individuals, a number of these variants are shared across diseases with diverse clinical presentations. This highlights the potential for improved autoimmune disease understanding which could be achieved by characterising the mechanism by which variants lead to increased risk of disease. Of particular interest is the potential for identifying novel drug targets or of repositioning drugs currently used in other diseases. The majority of autoimmune disease variants do not alter coding regions and it is often difficult to generate a plausible hypothetical mechanism by which variants affect disease-relevant genes and pathways. Given the interest in this area, considerable effort has been invested in developing and applying appropriate methodologies. Two of the most important technologies in this space include both low- and high-throughput genomic perturbation using the CRISPR/Cas9 system and massively parallel reporter assays. In this review, we introduce the field of autoimmune disease functional genomics and use numerous examples to demonstrate the recent and potential future impact of these technologies.
Late relapsing germ cell tumors with elevated tumor markers
Authors: Che Yue , Lusch Achim , Winter Christian , Große Siemer Robert , Buddensieck Carolin , Albers Peter , Hiester Andreas 
Published: September 2021

Abstract
Purpose
Late relapsing germ cell tumors (LR-GCT) are considered a rare distinct biologic entity as their clinical presentation and response to treatment is different to early recurrences. While serum tumor markers (AFP and ß-HCG) play an important role at the time of first diagnosis to correctly classify prognosis and treatment of germ cell tumors, they may not have the same significance in a late relapse situation.

Patients and methods
Thirty-seven patients with LR-GCT with elevated serum tumor markers were identified in our database. Twenty-six patients underwent primary surgical resection of the late relapsing tumor. Eleven patients received salvage chemotherapy and a post-chemotherapy residual tumor resection. Serum tumor markers, histological findings and oncological outcome were analyzed.

Results
In the histopathological specimen, viable cancer was found in 20 cases (54%) and teratoma was found in 16 cases (43%). In nine cases (24%), a somatic-type malignant transformation was present. In 19 of 37 patients (51.4%), the late relapse specimen presented a histological type of GCT, which was not present in the primary histology. Twenty-two patients (59.5%) were included in follow-up analysis. Mean and median follow-up time was 62.2 and 53 months, respectively. Seventeen patients (77.3%) suffered a relapse or had progressive disease after LR therapy. Five patients (22.7%) have been relapse-free after LR therapy (mean FU 61.6 months). Ten patients died of disease during follow-up (45.5%) and had a mean time from LR to death of 66.4 months. Eleven patients were alive at last follow-up (mean FU 62.2 months). Relapse and survival rate were similar between patients who received primary resection of LR tumor and patients who received salvage chemotherapy followed by surgery.

Conclusion
Patients with a late relapsing germ cell tumor and elevated markers have a poor prognosis and a high risk for another relapse independent on primary treatment. The histological type and aggressiveness of a late relapsing tumor cannot be predicted with serum tumor marker levels at the time of diagnosis of LR. In up to 54% of cases, primary histology did not coincide with LR histology. Therefore, we propose primary surgical resection of a late relapsing tumor if a complete resection is feasible in order to gain exact histology and tailor further treatment.
Salvage of limb salvage in oncological reconstructions of the lower limb with megaprosthesis: how much to push the boundaries?
Authors: Innocenti Matteo , Muratori Francesco , Foschi Lorenzo , Bartolini Saverio , Scorianz Maurizio , Scoccianti Guido , Campanacci Domenico Andrea 
Published: September 2021

Abstract
Introduction
Megaprosthesis represent the most commonly used limb salvage method after musculoskeletal tumor resections. Nevertheless, they are burdened by high complication rate, requiring several surgical revisions and eventually limb amputation. The aims of this study were to evaluate the effect of rescuing the limb with subsequent revisions on complication rates (a), incidence of amputations (b), and whether complications reduce functional outcome after the first surgical revision (c).

Materials and methods
We retrospectively reviewed 444 lower limb megaprosthesis implanted for primary musculoskeletal tumors or metastatic lesions, from February 2000 to November 2017. 59 patients received at least one revision megaprosthesis surgery. MSTS score was used to assess final functional results. Complication-revision-amputation free survival rates were calculated both at 5 and 10 years of follow-up.

Results
Complication free survival, revision free survival and amputation free survival at 10 years were 47% and 53%, 61% and 67%, 90% and 86% among all 444 patients and the group of 59 revised patients, respectively. The incidence of further complications after the first complication was 26% in the group treated with no subsequent revision surgeries and 51% in the group with at least one revision surgery. We found a trend of inverse linear relationship between the number of complications needing subsequent revision surgeries and the final MSTS.

Conclusion
The number of further revision surgeries after limb salvage with megaprosthesis increases the incidence of complications. Repeated surgical revisions, in particular after infection, increase the amputation rate. The most frequent causes of failure were structural failures and infections. MSTS score was superior for patients undergoing limb salvage than amputees. However, MSTS progressively decreased with multiple revisions becoming inferior to the functional score of an amputated patient.
Racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing for sensorineural hearing loss
Authors: Florentine Michelle M. , Rouse Stephanie L. , Stephans Jihyun , Conrad David , Czechowicz Josephine , Matthews Ian R. , Meyer Anna K. , Nadaraja Garani S. , Parikh Rajan , Virbalas Jordan , Weinstein Jacqueline E. , Chan Dylan K. 
Published: September 2021

AbstractUnderstanding racial and ethnic disparities in diagnostic rates of genetic testing is critical for health equity. We sought to understand the extent and cause of racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing (CGT) for sensorineural hearing loss (SNHL). We performed a retrospective cohort study at two tertiary children’s hospitals on a diverse cohort of 240 consecutive pediatric patients (76% publicly insured, 82% non-White) with SNHL of unknown etiology who underwent CGT. Definite and possible genetic diagnoses were assigned for each patient, representing the likelihood of a genetic cause of hearing loss. Associations between diagnostic rates were examined. 3.8 ± 2.1 variants were detected per patient; this frequency did not vary between White/Asian and Hispanic/Black cohorts. Overall, 82% of variants were variants of uncertain significance (VUS). Compared with White and Asian subjects, variants identified among Hispanic and Black children were less likely to be classified as pathogenic/likely pathogenic (15% vs. 24%, p < 0.001), and Hispanic and Black children were less likely to have a definite genetic diagnosis (10% vs. 37%, p < 0.001). The adjusted odds ratio for definite genetic diagnosis in Black and Hispanic children compared with White and Asian children was 0.19. Expanding genetic diagnostic criteria to include predicted deleterious VUSs reduced these disparities between White/Asian and Hispanic/Black children, with comparable molecular diagnostic rates (41% vs. 38%, p = 0.72). However, in silico predictions are insufficiently valid for clinical use. Increased inclusion of underrepresented groups in genetic hearing-loss studies to clinically validate these variants is necessary to reduce racial and ethnic disparities in diagnostic efficacy of comprehensive genetic testing.
A randomized controlled trial of stapled versus ultrasonic transection in distal pancreatectomy
Authors: Landoni Luca , De Pastena Matteo , Fontana Martina , Malleo Giuseppe , Esposito Alessandro , Casetti Luca , Marchegiani Giovanni , Tuveri Massimiliano , Paiella Salvatore , Pea Antonio , Ramera Marco , Borin Alex , Giardino Alessandro , Frigerio Isabella , Girelli Roberto , Bassi Claudio , Butturini Giovanni , Salvia Roberto 
Published: September 2021

AbstractBackgroundThe pancreatic transection method during distal pancreatectomy is thought to influence postoperative fistula rates. Yet, the optimal technique for minimizing fistula occurrence is still unclear. The present randomized controlled trial compared stapled versus ultrasonic transection in elective distal pancreatectomy.MethodsPatients undergoing distal pancreatectomy from July 2018 to July 2020 at two high-volume institutions were considered for inclusion. Exclusion criteria were contiguous organ resection and a parenchymal thickness > 17 mm on intraoperative ultrasound. Eligible patients were randomized in a 1:1 ratio to stapled transection (Endo GIA Reinforced Reload with Tri-Staple Technology®) or ultrasonic transection (Harmonic Focus® + or Harmonic Ace® + shears). The primary endpoint was postoperative pancreatic fistula. Secondary endpoints included overall complications, abdominal collections, and length of hospital stay.ResultsOverall, 72 patients were randomized in the stapled transection arm and 73 patients in the ultrasonic transection arm. Postoperative pancreatic fistula occurred in 23 patients (16%), with a comparable incidence between groups (12% in stapled transection versus 19% in ultrasonic dissection arm,p = 0.191). Overall complications did not differ substantially (35% in stapled transection versus 44% in ultrasonic transection arm,p = 0.170). There was an increased incidence of abdominal collections in the ultrasonic dissection group (32% versus 14%,p = 0.009), yet the need for percutaneous drain did not differ between randomization arms (p = 0.169). The median length of stay was 8 days in both groups (p = 0.880). Intraoperative blood transfusion was the only factor independently associated with postoperative pancreatic fistula on logistic regression analysis (OR 4.8, 95% CI 1.2–20.0,p = 0.032).ConclusionThe present randomized controlled trial of stapled versus ultrasonic transection in elective distal pancreatectomy demonstrated no significant difference in postoperative pancreatic fistula rates and no substantial clinical impact on other secondary endpoints.
Plant root development: is the classical theory for auxin-regulated root growth false?
Authors: Edelmann Hans G. 
Published: September 2021

AbstractOne of the longest standing theories and, therein-based, regulation-model of plant root development, posits the inhibitory action of auxin (IAA, indolylacetic acid) on elongation growth of root cells. This effect, as induced by exogenously supplied IAA, served as the foundation stone for root growth regulation. For decades, auxin ruled the day and only allowed hormonal side players to be somehow involved, or in some way affected. However, this copiously reiterated, apparent cardinal role of auxin only applies in roots immersed in solutions; it vanishes as soon as IAA-supplied roots are not surrounded by liquid. When roots grow in humid air, exogenous IAA has no inhibitory effect on elongation growth of maize roots, regardless of whether it is applied basipetally from the top of the root or to the entire residual seedling immersed in IAA solution. Nevertheless, such treatment leads to pronounced root-borne ethylene emission and lateral rooting, illustrating and confirming thereby induced auxin presence and its effect on the root — yet, not on root cell elongation. Based on these findings, a new root growth regulatory model is proposed. In this model, it is not IAA, but IAA-triggered ethylene which plays the cardinal regulatory role — taking effect, or not — depending on the external circumstances. In this model, in water- or solution-incubated roots, IAA-dependent ethylene acts due to its accumulation within the root proper by inhibited/restrained diffusion into the liquid phase. In roots exposed to moist air or gas, there is no effect on cell elongation, since IAA-triggered ethylene diffuses out of the root without an impact on growth.
Influences on the excitation behavior of lightweight planetary gearboxes
Authors: Theling Julian , Brimmers Jens , Brecher Christian 
Published: September 2021

AbstractOne of the main cost drivers in mechanical engineering is material. In order to reduce costs, but also to reduce CO2 emissions in mobile applications, increasing efforts are being made to reduce the mass of components. In gear development, power density as the ratio of transmittable power to gear weight has become one of the key quality criteria. However, saving material usually also leads to lower stiffness of the components. In combination with higher specific powers and the associated higher forces, higher deformations and displacements occur in the gear unit. The gear unit is more elastic overall.Within this paper a measuring cell is presented which allows to measure the influence of elastic deformations and additional misalignments on the excitation behavior. By means of this measuring cell, the influence of certain misalignments and different ring gear rim thicknesses are investigated. The results show modulated excitations and sidebands which are excited depending on the misalignment.
Automation of gearbox design
Authors: Fürst Marius , Götz Joshua , Otto Michael , Stahl Karsten 
Published: September 2021

AbstractIn order to respond to a shortened development time of today’s transmission systems, the automation of certain steps in the design process is essential for ensuring an efficient development process. Computer-aided tools are widely used for analyzing given design configurations because standardized methods are available to evaluate the load carrying capacity of all key components of a simple gear train, namely bearings, shafts and gears. At an early stage of development, requirements and restrictions need to be synthesized to design concepts. During this step, engineers typically rely on their experience and proven practice. Design optimization usually is achieved through an iterative and time-consuming process of analyzing and tuning towards an optimization objective. In this paper a time-saving, automated and systematic method for the design of weight optimized helical gearboxes is proposed. The underlying method has been derived from both, norms and guidelines, which exist for the design and layout of shafts, bearings and gear wheel bodies. Starting with only few input parameters, a detailed shaft geometry with different diameter sections can be derived. A discrete set of values from standard tables and rolling bearing catalogs represents the method’s framework for all realizable shaft diameters in each section. A mixed integer nonlinear optimization problem results from the interdependence between these distinct values. For this purpose, a systematic iterative approach has been developed and implemented in an established design program for gearbox systems. The algorithm uses the results drawn from an analytical calculation of the shaft load carrying capacity to directly adjust the shaft’s diameter and length values. The dimensioning of the wheel body, the service life calculation of rolling element bearings and the selection of specific machine elements are embedded in a systematic sequence. As a result, the model is capable to work out a weight-optimized gearbox that consists of gear meshes, shafts and bearings, taking all three components into consideration at a time.