bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory effect of adipose-derived stem cells in the treatment of pelvic organ prolapse
Authors: Wang Su , Gao Jian , Wang Maohuai , Chen Liquan , Zhang Xiaowei , Wang Xiaoyu 
Published: November 2019

Objective This study investigated the effect of recombinant human connective tissue growth factor (hCTGF) on rat adipose-derived stem cells (ADSCs) and explored the feasibility of using ADSCs to treat pelvic organ prolapse. Methods ADSCs were isolated from rat inguinal adipose tissue and characterized by flow cytometry and for osteogenic and adipogenic differentiation. ADSCs were treated with recombinant hCTGF and qRT-PCR was performed to detect collagen I and III expression on post-treatment days 7, 14, and 28. Osteogenic and adipogenic differentiation of ADSCs was performed to evaluate the effect of hCTGF. ADSCs were seeded in biological grafting materials, acellular porcine pericardium (APP) and acellular bovine pericardium (ABP), then implanted in the rat vagina. Histology was performed to observe inflammation among different groups. Results Collagen I and III expression in ADSCs was significantly increased, and the ability to differentiate into osteogenic and adipogenic lineages was diminished after hCTGF treatment. APP and ABP seeded with ADSCs significantly decreased inflammation and protected from degradation in vivo compared with APP and ABP only; ABP seeded with ADSCs had the lowest inflammation. Conclusion hCTGF regulates collagen I and III expression and induces ADSC differentiation in vitro. ADSCs decrease inflammation associated with APP and ABP in vivo.
Three-dimensional printing technologies in the fabrication of maxillofacial prosthesis: A case report
Authors: Cevik Pinar , Kocacikli Mustafa 
Published: November 2019

Purpose: Patients with maxillofacial deformities always seek for aesthetic prosthesis. Recently, three-dimensional printing technologies have been used for dental treatments on such patients. Case report: A 24-year-old man reported to the Department of Prosthodontics for replacement of his missing right ear induced by a trauma. A magnet-retained auricular prosthesis was planned for the patient. Three-dimensional scanning was performed on the healthy side by using a three-dimensional optical scanner and the data were mirrored. The mirrored image was then imported to a software and a virtual model of the future prosthesis was obtained for the defect side. A three-dimensional printer was used to fabricate a negative mold for the mirrored image by using additive manufacturing. Initially, an impression of the defect side was made; then, the cast model was obtained in a dental flask. Magnets of the prosthesis were inserted to the acrylic resin framework on the cast model. Room temperature vulcanized silicone elastomer was mixed and poured into the three-dimensionally fabricated mold. Then, the flask was placed over the negative mold firmly. After polymerization of the silicone, the auricular prosthesis was delivered to the patient and the patient was instructed to clean the prosthesis daily. Conclusions: Three-dimensional printing technology was used for the fabrication of the patient’s missing ear. This method eliminated the conventional laboratory steps and reduced the number of stages of the fabrication of a silicone prosthesis. The negative mold of the defect side allowed us a direct fabrication of the silicone prosthesis without a need for waxing or flasking procedures.
Weights of Fetal Membranes and Umbilical Cords: Correlation With Placental Pathology
Authors: Ma Lucy X , Levitan Daniel , Baergen Rebecca N 
Published: November 2019

Introduction Proper placental gross examination requires weighing the placental disc trimmed of fetal membranes and the umbilical cord. However, untrimmed placental weights are often reported, both in cases submitted for consultation and in publications. Thus, determining the contribution of membranes and cords to untrimmed placental weights would be helpful in estimating the true trimmed weight of placentas. We sought to report the average weights of membranes and cord in term placentas and to correlate these weights with common placental pathologies. Methods A total of 500 consecutive placentas delivered between 36 and 42 weeks gestational age were subjected to a modified grossing protocol, in which the weight of the trimmed and untrimmed placentas, fetal membranes, and umbilical cords were recorded. Acute chorioamnionitis, meconium, maternal vascular malperfusion, and fetal vascular malperfusion were included as pathologic correlates. Clinical data such as the presence of fetal hydrops, intrauterine growth restriction, intrauterine fetal demise, and maternal diabetes were also recorded. Results The mean weights of the trimmed placenta, fetal membranes, and umbilical cords were 442 g (180–805 g), 47.2 g (16–108 g), and 37.9 g (9–126 g), respectively. The fetal membranes and umbilical cord weights contributed a mean of 16% to the total untrimmed placental weight. Meconium was associated with heavier fetal membranes. Fetal vascular malperfusion was associated with longer umbilical cord and thus also with heavier umbilical cords. Maternal vascular malperfusion and intrauterine growth restriction were associated with lighter placentas. Discussion The trimmed placental disc weight may be estimated by subtracting 16% (ie, weight of the fetal membranes and umbilical cord) from the untrimmed placental weight, or alternatively by subtracting the mean weight of the membranes and umbilical cord. It is important to consider the effects of meconium, fetal and maternal vascular malperfusion, and intrauterine growth restriction on membrane and cord weights when estimating the trimmed placental disc weight.
Relationship Between Diurnal Cortisol Profile and Sleep Quality in Patients With Hepatocellular Carcinoma
Authors: Huang Tsai-Wei , Cheung Denise Shuk Ting , Xu Xinyi , Loh El-Wui , Lai Jun-Hung , Su Wei-Wen , Wu Shun-Sheng , Lin Chia-Chin 
Published: November 2019

Purpose: Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide. Sleep problems are common in HCC patients and may be attributable to disturbances in the circadian rhythm. Research into the role of circadian rhythms in sleep quality among HCC patients is lacking, however. This study investigated the relationship between the diurnal cortisol profile and sleep quality among HCC patients. We aimed to identify alterations in the diurnal cortisol profile in patients with HCC compared to healthy controls and investigate whether they were associated with poor sleep quality among HCC patients. Methods: Participants comprised 75 HCC patients and 33 healthy individuals. The Taiwanese version of the Pittsburgh Sleep Quality Index (PSQI-T) was administered to assess sleep quality. Saliva samples were collected on 3 consecutive days at five time points daily to measure diurnal cortisol levels. Results: In the HCC group, 89.3% of individuals were poor sleepers (PSQI-T > 5), whereas among healthy individuals, 30.3% were poor sleepers. While the healthy participants’ diurnal cortisol profile followed a typical pattern that peaked 30 min after waking and declined gradually throughout the day, the cortisol level in the HCC patients rebounded at bedtime. Higher cortisol levels were marginally correlated with poor sleep quality ( OR = 1.00007, p < .05). Conclusions: Our study suggests a potential association between disturbed circadian rhythm and poor sleep quality in HCC patients. Further investigation of the causal relationship between sleep and circadian rhythm is warranted.
Pilot study on a new intervention programme for geriatric hip fracture patient with sarcopenia
Authors: Cheung Mei Yan , Man Lok Chun , Ho Wing Hang Angela 
Published: November 2019

Introduction: Sarcopenia and osteoporosis increase the risk of fall, resulting in fragility fracture. Intervention programme on sarcopenic hip fracture was set up in our centre. Method: All patients aged ≥65 admitted to Caritas Medical Centre with operatively treated hip fracture and diagnosed with sarcopenia were included. Interventions include inpatient nursing education, dietary advice, therapist assessment and structured 12-week Geriatric Day Hospital (GDH) exercise programme. Those who are not eligible for GDH training were classified as control group. Changes in relative skeletal muscle mass index (RASM), muscle strength and functional scores were measured. Results: There were 11 intervention and 13 control patients. Both groups of patients were noted to have improvement in RASM, knee extension power of lower limbs and functional scores. Between-group analysis showed there was more improvement in injured limb extension power in the intervention group, although it is statistically insignificant (control group: 3.585 kg, intervention group: 5.827 kg, p = 0.147). There was no statistically significant difference in the 3-month change in RASM (control group: 0.581 kg/m2, intervention group: 0.347 kg/m2, p = 0.369) and functional scores. Conclusion: These sarcopenic hip fracture patients may be too frail to benefit from traditional exercise treatment for sarcopenia. However, more improvement in muscle strength was observed in the intervention group although not statistically significant. Intervention programme with exercise prescription in sarcopenic hip fracture patients may have the potential to improve the lower limb muscle strength. A more intensive and longer exercise training programme with incorporation into day rehabilitation model may be needed for these frail hip fracture patients.
FLT3 Inhibitor Resistant Cells Show Different Downstream Signaling Pathway Changes.
Authors: Kim Kyu-Tae , Piloto Obdulio , Small Donald 
Published: November 2019

Abstract
Receptor tyrosine kinase FLT3 plays an important role in leukemogenesis, especially in acute myeloid leukemia (AML). Tyrosine kinase inhibitors (TKI) targeting wild-type and mutant FLT3 have been developed and shown to have activity in clinical trials. However, as seen with Gleevac in CML, prolonged incubation with TKIs can select for resistant clones that may contribute to disease progression. To study resistance to TKIs against FLT3 we developed FLT3 inhibitor resistant cell lines by co-culturing MOLM14 and BaF3/ITD cells, expressing FLT3/ITD mutants with increasing concentrations of the FLT3 inhibitor CEP-701. The resulting cell lines, MOLM14(R) and BaF3/ITD(R) are resistant to CEP-701 induced cytotoxicity. MOLM14(R) is also resistant to other selective FLT3 TKIs including CEP-5214 and PKC412. In contrast, BaF3/ITD(R) cells were still sensitive to CEP5214 and PKC412. Western blot analysis reveals that CEP-701, CEP-5214 and PKC412 all still inhibit FLT3 in MOLM14(R) cells implying selection of a clone no longer dependent on FLT3 signaling. FLT3 phosphorylation is not inhibited by CEP-701 in BaF3/ITD(R) cells but is still inhibited by CEP-5214 and PKC412. Thus the BaF3/ITD(R) cells appear to remain FLT3-dependent. Sequencing of FLT3 from the resistant clones showed that the resistance was not the result of drug resistance mutations in FLT3/ITD. To investigate possible mechanisms of resistance in FLT3-dependent and FLT3-independent FLT3 inhibitor resistant cells, we examined pathways downstream of FLT3. Previously, we and others reported that constitutive FLT3 activation results in specific changes in gene expression in myeloid leukemic cells. As expected for cells with continued FLT3/ITD activation, Western blot analysis of BaF3/ITD(R) cells treated with CEP-701 show that they maintain activation of Erk/MAPK, Akt, and STAT5 pathways and induction of FLT3 dependent genes including Pim-1 and cMyc. In the apparently FLT3-independent MOLM-14(R) clones, inhibition of FLT3 activity resulted in decreased phosphorylation of downstream Akt and Stat5. However, we found Erk/MAPK phosphorylation and cMyc expression were not decreased in response to FLT3 TKI. This implies that whatever pathway has been selected for the ability to grow in this inhibitor is still feeding into this part of the downstream signaling pathway normally activated by FLT3/ITD. Thus, BaF3/ITD(R) FLT3-dependent and MOLM-14(R) FLT3 independent cells differ in response to several FLT3 inhibitors that results from the differences in their mechanisms of resistance.
Targeting BCR-Independent Proliferation of CLL Cells
Authors: Erik Slinger , Kater Arnon P. , Thijssen Rachel , Eldering Eric 
Published: November 2019

Abstract
The clinical success of PI3K and Btk inhibitors that block upstream BCR signals, has been primarily attributed to inhibition of adhesion and migration of CLL cells. However, the effects of these inhibitors on the proliferative capacity of CLL cells is largely unknown. Interestingly, in vitro BCR triggering does not induce proliferation of CLL cells. Instead, we have found that activated T cell-derived signals, specifically CD40L and IL-21, initiate CLL proliferation in vitro and can be traced in CLL lymph node samples from patients [Pascutti et al., Blood 2013]. Targeting the underlying signaling pathways may be clinically relevant, and therefore we aimed to characterize the molecular mechanisms underlying antigen-independent proliferation.
In the present study we applied CD40L/IL-21 stimulation to induce proliferation, and tested various specific kinase inhibitors for blocking potential. Surprisingly, the Btk inhibitor ibrutinib significantly suppressed CD40L/IL-21-induced proliferation (Figure 1). Similarly, inhibition of PI3Kδ with idelalisib dampened proliferation. While neither ibrutinib nor idelalisib affected CD40L-induced NF-kB or IL-21 induced STAT3 phosphorylation, both compounds efficiently blocked downstream ERK1/2 phosphorylation. Impact of idelalisib and ibrutinib was non-synergistic, suggesting that PI3K and Btk are acting in concert. In contrast with the inhibitory effects of the two compounds above, no effect of CD40L/IL-21 induced proliferation was observed following inhibition of SYK activity with R406 (tamatinib). This strongly suggests a role for PI3K and Btk signaling independent of BCR-signaling.
We demonstrate that antigen-independent proliferation completely depends on downstream CDK4-activity, which can be blocked by the CDK4-inhibitor PD0332991.
IL-21 signaling is absolutely required for antigen-independent proliferation as treatment with the pan-JAK inhibitor INCB abrogates proliferation. Moreover, immunohistochemical staining of lymph nodes from CLL patients indicated the presence of phospho-STAT3 in CLL cells at lymph node sites, suggesting a contribution of JAK/STAT signaling to in vivo proliferation.
In conclusion, our data strongly suggest that non-BCR signals contribute to proliferation of CLL cells. Since the most recent clinical data point to development of resistance against ibrutinib, targeting non-BCR pathways may offer additional venues for treatment.
Figure 1. CD40L/IL-21 induced proliferation can be inhibited with kinase inhibitors that target kinases involved in BCR-signaling Figure 1. CD40L/IL-21 induced proliferation can be inhibited with kinase inhibitors that target kinases involved in BCR-signaling

Disclosures
No relevant conflicts of interest to declare.
Markers of autoimmunity in immune thrombocytopenia: prevalence and prognostic significance
Authors: Hollenhorst Marie A. , Al-Samkari Hanny , Kuter David J. 
Published: November 2019

Key Points
There is a high prevalence of autoimmune markers in patients with ITP. An increased risk of thrombosis was observed in patients with ITP with a positive lupus anticoagulant or antinuclear antibody.
Zebra leaf 15, a receptor-like protein kinase involved in moderate low temperature signaling pathway in rice
Authors: Feng Ping , Shi Junqiong , Zhang Ting , Zhong Yuqin , Zhang Lisha , Yu Guoling , Zhang Tianquan , Zhu Xiaoyan , Xing Yadi , Yin Wuzhong , Sang Xianchun , Ling Yinghua , Zhang Changwei , Yang Zhenglin , He Guanghua , Wang Nan 
Published: November 2019

Abstract
Background
Zebra leaf mutants are an important resource for studying leaf colour in rice. In most such mutants, the zebra leaf phenotype results from defective chloroplast biogenesis. The molecular mechanism by which zebra leaves develop remains unclear, so additional zebra-leaf mutants need to be identified.

Results
We isolated a novel rice zebra-leaf mutant, named zebra leaf 15 (z15), which showed transversely striped leaves with yellow-green or white-green sectors, in which chloroplast structure was disturbed. Transmission electron microscopy revealed that the structure of various organelles was impaired in yellow/white sectors. Z15, a single-copy gene in the rice genome, encodes a receptor-like protein kinase. Subcellular localization analysis indicates that Z15 and z15 are localized on the plasma membrane. The expression of Z15 is induced by moderate low temperature (18 °C). The mutation of Z15 influenced the expression of two downstream genes, OsWRKY71 and OsMYB4, that were responsive to moderate low temperature. The results show that Z15 plays a crucial role in the early stages of the response to moderate low temperature in rice.

Conclusions
We identified a novel zebra-leaf mutant (z15) that impaired chloroplast structure in rice, LOC_Os05g12680, encoding a receptor-like protein kinase. Further study indiceted that Z15 plays a crucial role in the early stages of the response to moderate low temperature in rice.
Deletion of the fungus specific protein phosphatase Z1 exaggerates the oxidative stress response in Candida albicans
Authors: Szabó Krisztina , Jakab Ágnes , Póliska Szilárd , Petrényi Katalin , Kovács Katalin , Issa Lama Hasan Bou , Emri Tamás , Pócsi István , Dombrádi Viktor 
Published: November 2019

Abstract
Background
Candida albicans is an opportunistic pathogen which is responsible for widespread nosocomial infections. It encompasses a fungus specific serine/threonine protein phosphatase gene, CaPPZ1 that is involved in cation transport, cell wall integrity, oxidative stress response, morphological transition, and virulence according to the phenotypes of the cappz1 deletion mutant.

Results
We demonstrated that a short-term treatment with a sublethal concentration of tert-butyl hydroperoxide suppressed the growth of the fungal cells without affecting their viability, both in the cappz1 mutant and in the genetically matching QMY23 control strains. To reveal the gene expression changes behind the above observations we carried out a global transcriptome analysis. We used a pilot DNA microarray hybridization together with extensive RNA sequencing, and confirmed our results by quantitative RT-PCR. Novel functions of the CaPpz1 enzyme and oxidative stress mechanisms have been unraveled. The numbers of genes affected as well as the amplitudes of the transcript level changes indicated that the deletion of the phosphatase sensitized the response of C. albicans to oxidative stress conditions in important physiological functions like membrane transport, cell surface interactions, oxidation-reduction processes, translation and RNA metabolism.

Conclusions
We conclude that in the wild type C. albicans CaPPZ1 has a protective role against oxidative damage. We suggest that the specific inhibition of this phosphatase combined with mild oxidative treatment could be a feasible approach to topical antifungal therapy.
Persistent and sporadic Listeria monocytogenes strains do not differ when growing at 37 °C, in planktonic state, under different food associated stresses or energy sources
Authors: Taylor Alexander J. , Stasiewicz Matthew J. 
Published: November 2019

Abstract
Background
The foodborne pathogen Listeria monocytogenes causes the potentially lethal disease listeriosis. Within food-associated environments, L. monocytogenes can persist for long periods and increase the risk of contamination by continued presence in processing facilities or other food-associated environments. Most research on phenotyping of persistent L. monocytogenes’ has explored biofilm formation and sanitizer resistance, with less data examining persistent L. monocytogenes’ phenotypic responses to extrinsic factors, such as variations in osmotic pressure, pH, and energy source availability. It was hypothesized that isolates of persistent strains are able to grow, and grow faster, under a broader range of intrinsic and extrinsic factors compared to closely related isolates of sporadic strains.

Results
To test this hypothesis, 95 isolates (representing 74 isolates of 20 persistent strains and 21 isolates of sporadic strains) from a series of previous studies in retail delis, were grown at 37 °C, in (i) stress conditions: salt (0, 5, and 10% NaCl), pH (5.2, 7.2, and 9.2), and sanitizer (benzalkonium chloride, 0, 2, and 5 μg/mL) and (ii) energy sources: 25 mM glucose, cellobiose, glycogen, fructose, lactose, and sucrose; the original goal was to follow up with low temperature experiments for treatments where significant differences were observed. Growth rate and the ability to grow of 95 isolates were determined using high-throughput, OD600, growth curves. All stress conditions reduced growth rates in isolates compared to control (p < 0.05). In addition, growth varied by the tested energy sources. In chemically defined, minimal media there was a trend toward more isolates showing growth in all replicates using cellobiose (p = 0.052) compared to the control (glucose) and fewer isolates able to grow in glycogen (p = 0.02), lactose (p = 2.2 × 10− 16), and sucrose (p = 2.2 × 10− 16). Still, at least one isolate was able to consistently grow in every replicate for each energy source.

Conclusions
The central hypothesis was rejected, as there was not a significant difference in growth rate or ability to grow for retail deli isolates of persistent strains compared to sporadic strains for any treatments at 37 °C. Therefore, these data suggest that persistence is likely not determined by a phenotype unique to persistent strains grown at 37 °C and exposed to extrinsic stresses or variation in energy sources.