bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel mouse model to study fracture healing of the proximal femur
Authors: Haffner‐Luntzer Melanie , Weber Birte , Lam Charles , Fischer Verena , Lackner Ina , Ignatius Anita , Kalbitz Miriam , Marcucio Ralph S. , Miclau Theodore 
Published: March 2020

AbstractThe majority of fractures, especially in elderly and osteoporotic patients, occurs in metaphyseal bone. However, only a few experimental models exist to study metaphyseal bone healing in mice. Currently used mouse models of metaphyseal fracture healing are either based on drill hole defects, lacking adequate biomechanical stimulation at the site of fracture and therefore endochondral ossification in the fracture callus, or are introduced into the distal part of the mouse femur stabilized by a locking plate, which is challenging due to the small specimen size. Therefore, the aim of the current study was to develop a new mouse model to study metaphyseal fracture healing of the proximal femur. We chose a combination between an open osteotomy and a closed intramedullary stabilization. A 24 G needle was inserted into the femur in a closed manner, then an osteotomy was made with a 0.4‐mm Gigli wire saw between the third and the lesser trochanter of the femur using an open approach. Fractured femurs were analyzed using microcomputed tomography and histology at days 14 and 21 after surgery. No animals were lost due to surgery or anesthesia. All animals displayed normal limb loading and a physiological gait pattern within the first three days after fracture. We found robust endochondral ossification during the fracture healing process with high expression of late chondrocyte and early osteogenic markers at day 14 (d14). By day 21 (d21), all fractures had a bony bridging score of 3 or more, indicating successful healing. Callus volume significantly decreased from d14 to d21, whereas high numbers of osteoclasts appeared at the fracture callus until d21, indicating that callus remodeling had already started at d21. In conclusion, we successfully developed a novel mouse model to study endochondral fracture healing of the proximal femur. This model might be useful for future studies using transgenic animals to unravel molecular mechanisms of osteoporotic metaphyseal fracture healing.
HELP YOUR WORKFORCE CLOSE THEIR POWER GAPS AND ACHIEVE EXPONENTIAL GROWTH
Authors: Caprino Kathy 
Published: March 2020

AbstractThe author notes that professionals long to be involved in initiatives that will generate great success and hope to experience personal reward and meaning doing that work. But in her experience and research in the past 15 years, she has observed that many are failing to experience the success and reward they need and want. She noticed some common, repetitive patterns emerging in terms of what professionals were dealing with in their careers and jobs and pulled back the lens to identify what’s at the heart of this widespread experience of unhappiness, disillusionment, and disengagement. The article proceeds from addressing a core question: “What is missing from the lives of professional men and women who feel they can’t experience the joy, success, reward and impact they deserve and want?” Seven specific career‐thwarting “power gaps” professionals face are identified and examined in detail: (1) not recognizing your special talents, abilities, and accomplishments; (2) communicating from fear not strength; (3) reluctance to ask for what you deserve; (4) isolating from influential support; (5) acquiescing instead of saying “STOP!” to mistreatment; (6) losing sight of your thrilling dream; and (7) allowing past trauma to shape and define you.
Binge watching: An exploration of the role of technology
Authors: Nanda Ambika Prasad , Banerjee Ranjan 
Published: March 2020

AbstractWatching television shows in quick succession on the Netflix and Amazon Prime platforms is on the rise. Although widespread, this binge watching behavior has received limited attention from marketing academics. The current study conceptualizes binge watching needs and examines their effect on the gratifications obtained from binge watching. We apply the lens of uses and gratifications (U&G) theory for model development and test the model empirically, using data from two cities in India. We add a new category of needs, namely technology‐related needs, to the existing psycho‐sociological‐related needs (named as content‐related needs in this paper) present in plain‐old‐television studies (POTS). We find that a technology‐related need—that is, modal experience (the presence of media content in various formats leading to superior experience)—significantly impacts gratification from binge watching. We also find a strong moderating effect of self‐control, used in previous studies of binge‐eating and binge‐shopping, in which the effect of modal experience, navigability and parasocial interaction need gratification is heightened for consumers who have low levels of self‐control. We build on these findings to suggest implications for marketers, advertisers, and consumer‐advocacy groups.
Classical homocystinuria: A common inborn error of metabolism? An epidemiological study based on genetic databases
Authors: Weber Hoss Giovana R. , Sperb‐Ludwig Fernanda , Schwartz Ida V. D. , Blom Henk J. 
Published: March 2020

AbstractBackgroundBiallelic pathogenic variants in CBS gene cause the most common form of homocystinuria, the classical homocystinuria (HCU). The worldwide prevalence of HCU is estimated to be 0.82:100,000 [95% CI, 0.39–1.73:100,000] according to clinical records and 1.09:100,000 [95% CI, 0.34–3.55:100,000] by neonatal screening. In this study, we aimed to estimate the minimal worldwide incidence of HCU.MethodsThe 25 most common pathogenic alleles of HCU were identified through a literature review. The incidence of HCU was estimated based on the frequency of these common pathogenic alleles in a large genomic database (gnomAD).ResultsThe minimum worldwide incidence of HCU was estimated to be ~0.38:100,000, and the incidence was higher in Europeans non‐Finnish (~0.72:100,000) and Latin Americans (~0.45:100,000) and lower in Africans (~0.20:100,000) and Asians (~0.02:100,000).ConclusionOur data are in accordance with the only published metanalysis on this topic. To our surprise, the observed incidence of HCU in Europeans was much lower than those described in articles exploring small populations from northern Europe but was similar to the incidence described on the basis of neonatal screening programs. In our opinion, this large dataset analyzed and its population coverage gave us greater precision in the estimation of incidence.
Trends in opioid prescribing in Estonia (2011‐2017)
Authors: Uusküla Anneli , Raag Mait , Kurvits Katrin , Laius Ott , Uusküla Maia , Oselin Kersti 
Published: March 2020

AbstractOur objective was to examine the trends and variation in opioid prescribing in Estonia from 2011 to 2017. This retrospective cross‐sectional study is based on a nationwide prescription medicines database. We stratified the analysis by treatment indication (cancer vs noncancer pain). Between 2011 and 2017, annual opioid prescribing rates increased by 67% (from 82.9 to 138.6 prescriptions per 1000 population). The annual number of prescriptions per patient did not change substantially (from 2.94 in 2011 to 2.87 in 2017), and was higher among cancer patients (5.07 vs 2.67 annual prescriptions per cancer and noncancer patients, respectively, in 2017). The use of the most potent opioids (morphine, fentanyl) was higher in noncancer than in cancer patients. The use of prescription opioids is low, and raises concern about the potential undertreatment of cancer pain, in parallel with misuse of opioids for either noncancer pain or diversion.
Beta human papillomaviruses infection and skin carcinogenesis
Authors: Bandolin Luigia , Borsetto Daniele , Fussey Jonathan , Da Mosto Maria Cristina , Nicolai Piero , Menegaldo Anna , Calabrese Luca , Tommasino Massimo , Boscolo‐Rizzo Paolo 
Published: March 2020

SummaryDuring the last decade, the worldwide incidence of keratinocyte carcinomas (KC) has increased significantly. They are now the most common malignancy, representing approximately 30% of all cancers. The role of ultraviolet (UV) radiation as a major environmental risk factor for skin cancers is well recognized. The aim of this review is to analyse the current understanding of the nature of beta‐human papillomavirus (HPV) and its association with KC and explore the implications for the management and prevention of these cancers. A comprehensive review of the literature on beta‐HPV and its association with KC was undertaken, the results reported in the form of a narrative review. A subgroup of HPV that infects the mucosal epithelia of the genital tract has been firmly associated with carcinogenesis. In addition, some HPV types with cutaneous tropism have been proposed to cooperate with UV in the development of KC. The first evidence for this association was reported in 1922 in patients with epidermodysplasia verruciformis (EV). Since then, epidemiological studies have highlighted the higher risk of skin cancer in patients with EV and certain cutaneous HPV types, and in vitro studies have elucidated molecular mechanisms and transforming properties of beta‐HPV. Furthermore, in vivo research conducted on transgenic mice models has shown the possible role of beta‐HPV in cutaneous carcinogenesis as a co‐factor with UV radiation and immunosuppression. There is good evidence supporting the role of beta‐HPV in the oncogenesis of KC. The high prevalence of beta‐HPV in human skin and the worldwide burden of KC makes the search for an effective vaccine relevant and worthwhile.
Use of bankruptcy methods for resolving interprovincial water conflicts over transboundary river: Case study of Indus River in Pakistan
Authors: Janjua Shahmir , Hassan Ishtiaq 
Published: March 2020

AbstractSustainable transboundary water governance is often challenged by conflicts between agents, which necessitates the design of cooperative and self‐enforcing alternatives to facilitate equitable water distribution. A pervasive and critical problem related to many transboundary rivers is that the total allocation or demand of riparian states is usually much more than that of the total available water. This problem is a major cause of disputes, both nationally and internationally. A key challenge concerns how to allocate the available water among riparian states with competing and often conflicting needs under an uncertain supply–demand gap. To address this pervasive allocation problem related to transboundary rivers, the bankruptcy method is used. The bankruptcy method distributes water among riparian states when their total demand exceeds the total available water. We investigate the utility of this method in the Indus River – a river that is shared among the four provinces of Pakistan, namely, Punjab, Sindh, Baluchistan and Khyber Pakhtunkhwa (KPK) – using five commonly used bankruptcy rules and the Shapely value. Two new bankruptcy rules namely the “groundwater‐based rule” and “the proposed rule” are also proposed to address the usage of groundwater: the land affected by salinity and the gross domestic product (GDP) of each province. Additionally, this paper introduces a new method to compare and contrast the bankruptcy rules, the Shapely value and the two proposed rules. The findings suggest that the groundwater‐based rule has the lowest dispersion and is the preferred method for water allocation in the Indus River Basin. The use of the bankruptcy rules, the Shapely value and the two proposed methods has the potential to address the supply–demand mismatches of shared rivers. The proposed framework for selecting the best rule is recommended as an effective tool to facilitate negotiation over practical water allocation within transboundary river basins.
Cerebrolysin ameliorates prefrontal cortex and hippocampus neural atrophy of spontaneous hypertensive rats with hyperglycemia
Authors: Aguilar‐Hernández Leonardo , Gómez‐Villalobos Maria de Jesús , Flores Gonzalo 
Published: March 2020

AbstractHyperglycemia of diabetes mellitus causes damage at the vascular level, which at the renal level represents diabetic nephropathy. In this pathology, there is arterial hypertension. In addition, several reports suggest that hyperglycemia and arterial hypertension affect interneuronal communication at the level of dendritic morphology. We studied these changes in an animal model with streptozotocin‐induced diabetes mellitus in the spontaneous hypertensive (SH) rat. Recent reports from our laboratory have demonstrated that cerebrolysin (CBL), a preparation of neuropeptides with protective and repairing properties, reduces dendritic deterioration in both pathologies, in separate studies. In the present study, we evaluated the effect of CBL using the animal model with hyperglycemia and arterial hypertension and assessed the dendritic morphology using a Golgi‐Cox staining procedure. Our results suggest that CBL ameliorated the reduction in the number of dendritic spines in the PFC and hippocampus caused by hyperglycemia in the SH rat. In addition, CBL also increased distal dendritic length in the PFC and hippocampus in hyperglycemic SH rats. Consequently, the CBL could be a therapeutic tool used to reduce the damage at the level of dendritic communication present in both pathologies.
Photodynamic therapy and laser‐assisted drug delivery and R0 excision in the treatment of an immunosuppressed patient showing multiple actinic keratosis and recurrent squamous cell carcinoma: A case report
Authors: Bigge Bianca , Ungerechts Gerd , Bigge Stefan 
Published: March 2020

AbstractWe report on a 73‐year‐old male patient with granulomatosis with polyangiitis (Wegener's granulomatosis) who developed increasingly growing lesions of actinic keratosis (AK) and squamous cell carcinoma (SCC) of the scalp under systemic immunomodulatory therapy with azathioprine for more than 8 years. The patient underwent a first‐line surgical therapy resulting in histologically confirmed R0 resection status followed by topical imiquimod treatment and cryotherapy. However, recurrence of AK/SCC progression could not be stopped sufficiently. Therefore, due to the difficult localization of the lesions at the head and the limitation of further surgical procedures, the patient was presented to our laser medicine department in order to consider complementary therapy options. The therapy approach was combining photodynamic therapy (PDT) with laser‐assisted drug delivery (LADD). PDT has been successful in treating field cancerization for decades, but it has limitations in the treatment of hyperkeratotic lesions. Pre‐treatment with LADD can be used to optimize the penetration depth of the prodrug 5‐aminolevulinic acid (BF‐200 ALA, Ameluz) and significantly increase the bioavailability as well as inducing an inflammatoric reaction. Following this therapeutic approach, we were able to achieve a stable disease over a follow‐up period of 2 years after six sessions of combined LADD + PDT.
Poisonous substances used to capture and kill the greater cane rat (Thryonomys swinderianus)
Authors: Essuman Edward K. , Duah Kingsley K. 
Published: March 2020

AbstractThe greater cane rat, as it is commonly known, is often called grasscutter (in Ghana, Nigeria and other regions of West Africa). Even though is highly patronized as a delicacy by a majority of Ghanaians (akrantie—Twi language) mostly in the rural areas, the persistent reports on people being poisoned as a result of eating food prepared with grasscutter which has been captured/killed by the use of poison are deterring people from consuming the grasscutter meat despite its high protein content. The objective of this study was, therefore, to investigate the actual ingredients that are used in the formulation of poison to capture grasscutter for human consumption. Questionnaires were administered to participants (farmers) who are involved in grasscutter hunting to solicit the ingredient they formulate to poison the grasscutter in their hunting. To prove the activeness of these ingredients, the main ingredient used in formulating the poison to capture the grasscutters were tested on two male grasscutters and these were yellow oleander root (Cascabela thevetia; syn: Thevetia peruviana) powder and carbofuran. The findings of the experimental trial revealed that the grasscutter that was fed with yellow oleander root powder did not die but showed some signs of intoxication and staggered each time it tried to move. However, the grasscutter fed with carbofuran died within 10 hr of being poisoned. Majority of the participants attested to the fact that the use of poison increases their chance of capturing the grasscutter, especially in the dry season since the poison is not washed away by the rainwater. However, consuming grasscutter poisoned with either yellow oleander root power or carbofuran could be detrimental to human health.
On generalized Q-systems
Authors: Bajnok Zoltán , Granet Etienne , Jacobsen Jesper Lykke , Nepomechie Rafael I. 
Published: March 2020

Abstract
We formulate Q-systems for the closed XXZ, open XXX and open quantum- group-invariant XXZ quantum spin chains. Polynomial solutions of these Q-systems can be found efficiently, which in turn lead directly to the admissible solutions of the corresponding Bethe ansatz equations.
One-loop universality of holographic codes
Authors: Dong Xi , Marolf Donald 
Published: March 2020

Abstract
Recent work showed holographic error correcting codes to have simple universal features at O(1/G). In particular, states of fixed Ryu-Takayanagi (RT) area in such codes are associated with flat entanglement spectra indicating maximal entanglement between appropriate subspaces. We extend such results to one-loop order (O(1) corrections) by controlling both higher-derivative corrections to the bulk effective action and dynamical quantum fluctuations below the cutoff. This result clarifies the relation between the bulk path integral and the quantum code, and implies that i) simple tensor network models of holography continue to match the behavior of holographic CFTs beyond leading order in G, ii) the relation between bulk and boundary modular Hamiltonians derived by Jafferis, Lewkowycz, Maldacena, and Suh holds as an operator equation on the code subspace and not just in code-subspace expectation values, and iii) the code subspace is invariant under an appropriate notion of modular flow. A final corollary requires interesting cancelations to occur in the bulk renormalization-group flow of holographic quantum codes. Intermediate technical results include showing the Lewkowycz-Maldacena computation of RT entropy to take the form of a Hamilton-Jacobi variation of the action with respect to boundary conditions, corresponding results for higher-derivative actions, and generalizations to allow RT surfaces with finite conical angles.
Microwave Ablation in the Proximity of Surgical Clips: Is there a Safety Issue?
Authors: Liebl Martin , Schulze-Hagen Maximilian , Zimmermann Markus , Pedersoli Federico , Kuhl Christiane , Bruners Philipp , Isfort Peter 
Published: March 2020

Abstract
Purpose
The purpose of this study was to evaluate the heat generation of surgical clips within the target area of MWA and the influences on the ablation volume.

Materials and Methods
In bovine liver tissue, 42 ex vivo microwave ablations (60 W; 180 s) were performed. During ablation, the temperature was measured continuously at 4 points of interest (POI), in a distance of 7.5 and 15 mm on each side of the microwave antenna, with a titanium surgical placed at one 7.5-mm POI. Ablation volumes containing large vessels (n = 10) were excluded. For every POI, the mean temperature of 32 ablations was calculated. The mean temperatures were compared between the 4 POI and statistically analyzed using the Student’s t test.

Results
The mean maximum temperatures at the side of the clip were 88.76 °C/ 195 s and 52.97 °C/ 195 s and at the side without clip 78.75 °C/ 195 s and 43.16 °C/ 195 s, respectively, at POI 7.5 mm and POI 15 mm. The maximum difference of mean temperatures for POI 7.5 mm was 12.91 °C at 84 s (p = 0.022) and for POI 15 mm 9.77 °C at 195 s (p = 0.009). No significant changes in size and shape of the ablation zone could be determined.

Conclusions
Our study demonstrated significantly higher temperatures adjacent to surgical clips. Also, the temperatures distal to the titanium clip were higher compared to the control location without clip. These findings suggest an increased risk of thermal damage to surrounding tissues during MWA, especially in case of immediate contact to surgical clips.
Phase 1 study of napabucasin, a cancer stemness inhibitor, in patients with advanced solid tumors
Authors: Kawazoe Akihito , Kuboki Yasutoshi , Bando Hideaki , Fukuoka Shota , Kojima Takashi , Naito Yoichi , Iino Shuichi , Yodo Yasuhide , Doi Toshihiko , Shitara Kohei , Yoshino Takayuki 
Published: March 2020

Abstract
Purpose
Napabucasin is a cancer stemness inhibitor that targets a number of oncogenic pathways, including signal transducer and activator of transcription 3 (STAT3). Phase 1/2 studies suggest tolerability and anti-tumor activity in various types of cancer; a Phase 3 study of napabucasin plus standard therapy in colorectal cancer is ongoing. This is a Phase 1 dose-escalation study in patients with advanced solid tumors, and the first study of napabucasin in Japanese patients.

Methods
Patients received napabucasin 480, 960, or 1440 mg daily in 28-day cycles until disease progression or intolerable toxicity. Primary objectives were to determine dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and the pharmacokinetic (PK) profile of napabucasin. Blood samples were taken for PK analysis on Days 1, 2, 8, and 15 of Cycle 1, and Days 29 and 30 of Cycle 2. Secondary objectives were to assess napabucasin antitumor activity, and the relationship between biomarkers and antitumor activity. JapicCTI-No: JapicCTI-132152.

Results
Enrolled were 14 patients (480 mg [n = 3], 960 mg [n = 4], 1440 mg [n = 7]). One patient experienced a DLT (Grade 3, anorexia). MTD was 1440 mg/day. Most common drug-related adverse events were diarrhea (n = 9), nausea (n = 4), vomiting (n = 3), and anorexia (n = 3). Napabucasin showed a similar PK profile to previous studies and no abnormal accumulation was observed. Following treatment, two patients had stable disease; the remaining 12 had progressive disease.

Conclusion
Napabucasin was well-tolerated at doses up to 1440 mg/day in Japanese patients with advanced solid tumors; the PK profile was comparable to that reported previously.
Fungal Kti12 proteins display unusual linker regions and unique ATPase p-loops
Authors: Krutyhołowa Rościsław , Reinhardt-Tews Annekathrin , Chramiec-Głąbik Andrzej , Breunig Karin D. , Glatt Sebastian 
Published: March 2020

AbstractKti12 (Kluyveromyces lactis toxin insensitive 12) is an evolutionary highly conserved ATPase, crucial for the tRNA-modification activity of the eukaryotic Elongator complex. The protein consists of an N-terminal ATPase and a C-terminal tRNA-binding domain, which are connected by a flexible linker. The precise role of the linker region and its involvement in the communication between the two domains and their activities remain elusive. Here, we analyzed all available Kti12 protein sequences and report the discovery of a subset of Kti12 proteins with abnormally long linker regions. These Kti12 proteins are characterized by a co-occurring lysine to leucine substitution in their Walker A motif, previously thought to be invariable. We show that the K14L substitution lowers the affinity to ATP, but does not affect the catalytic activity of Kti12 at high ATP concentrations. We compare the activity of mutated variants of Kti12 in vitro with complementation assays in vivo in yeast. Ultimately, we compared Kti12 to other known p-loop ATPase family members known to carry a similar deviant Walker A motif. Our data establish Kti12 of Eurotiomycetes as an example of eukaryotic ATPase harboring a significantly deviating but still functional Walker A motif.