bluuebunny/crossref_metadata_2025 huggingface dataset:
Distinct genomic signals of lifespan and life history evolution in response to postponed reproduction and larval diet inDrosophila
Authors: Hoedjes Katja M. , van den Heuvel Joost , Kapun Martin , Keller Laurent , Flatt Thomas , Zwaan Bas J.
Published: October 2019

Reproduction and diet are two major factors controlling the physiology of aging and life history, but how they interact to affect the evolution of longevity is unknown. Moreover, although studies of large-effect mutants suggest an important role of nutrient sensing pathways in regulating aging, the genetic basis of evolutionary changes in lifespan remains poorly understood. To address these questions, we analyzed the genomes of experimentally evolved Drosophila melanogaster populations subjected to a factorial combination of two selection regimes: reproductive age (early versus postponed), and diet during the larval stage (“low,” “control,” “high”), resulting in six treatment combinations with four replicate populations each. Selection on reproductive age consistently affected lifespan, with flies from the postponed reproduction regime having evolved a longer lifespan. In contrast, larval diet affected lifespan only in early-reproducing populations: flies adapted to the “low” diet lived longer than those adapted to control diet. Here, we find genomic evidence for strong independent evolutionary responses to either selection regime, as well as loci that diverged in response to both regimes, thus representing genomic interactions between the two. Overall, we find that the genomic basis of longevity is largely independent of dietary adaptation. Differentiated loci were not enriched for “canonical” longevity genes, suggesting that naturally occurring genic targets of selection for longevity differ qualitatively from variants found in mutant screens. Comparing our candidate loci to those from other “evolve and resequence” studies of longevity demonstrated significant overlap among independent experiments. This suggests that the evolution of longevity, despite its presumed complex and polygenic nature, might be to some extent convergent and predictable.
Nondestructive detection of apple crispness via optical fiber spectroscopy based on effective wavelengths
Authors: Ni Fupeng , Zhu Xiaowen , Gu Fang , Hu Yaohua
Published: October 2019

Crispness is regarded as a significant quality index for apples. Currently, destructive sensory evaluation is the accepted method used to detect apple crispness, making it essential to develop a method that can detect apple crispness in a nondestructive manner. In this study, spectroscopy was proposed as the nondestructive technique for detecting apples' crispness, ultimately obtaining a spectral reflectance curve between 450 nm and 1,000 nm. In order to simplify and improve modeling efficiency, successive projections algorithm (SPA) and x‐loading weights (x‐LW) methods were used to select the most effective wavelengths. Partial least squares (PLS) algorithm, radial basis neural networks (RBNN), and multilayer perceptron neural networks (MLPNN) methods were used to establish the models and to predict the crispness of “Fuji” and “Qinguan” apple varieties. Based on the full wavelength (FW), the prediction accuracy of the PLS model for “Fuji” and “Qinguan” apple varieties was 92.05% and 95.87%, respectively. The effective wavelengths selected via SPA for the “Fuji” apple variety were 450.41 nm, 476.80 nm, 677.75 nm, and 750.72 nm, and the effective wavelengths selected via x‐LW for the “Qinguan” apple variety were 542.51 nm, 544.79 nm, 676.96 nm, and 718.29 nm. The prediction accuracy of the PLS model based on effective wavelengths for “Fuji” and “Qinguan” apple varieties reached 91.31% and 96.41%, respectively. Compared with the RBNN model, the MLPNN model achieved better prediction results for both “Fuji” and “Qinguan” apples, with the prediction accuracy reaching 97.8% and 99.9%, respectively. Based on the above findings, effective wavelength selection and MLPNN modeling were able to detect apple crispness with the highest accuracy. Overall, it can be concluded that the less effective wavelengths are conducive to developing an instrument for crispness detection.
A Champion for the Unestablished
Authors: Rarrick Mohini P. B.
Published: October 2019

As a student in bioethics, I knew that The Hastings Center and its founders were the height of excellence in this field, and therefore I found them both intimidating and intriguing. When I began working there, Dan Callahan was supportive of my endeavors to provide a venue for students and other young writers to express their views on bioethics. I started my own blog called Bioethx under 25 that featured short essays by anyone who wished to submit, generally individuals who had a genuine philosophical interest but were not yet at the level of pursuing a Ph.D. Dan's support of my project culminated in his sponsorship of the Daniel Callahan Young Writer's Prize, an essay contest run through the blog. This was one of the many ways he demonstrated that making theoretical contributions to bioethics should not be limited to a select few.
Animals with Human Cells in Their Brains: Implications for Research
Authors: Maschke Karen J.
Published: October 2019

In “Human‐Animal Chimeras: The Moral Insignificance of Uniquely Human Capacities,” Julian Koplin argues against the views that all uniquely human traits have moral significance or that all the traits humans have in common with other animals “are morally insignificant.” He recommends instead the adoption of “a better framework for thinking about the moral status of part‐human beings,” one that emphasizes the “phenomenal value (or disvalue)” chimeric animals are likely “to enjoy (or suffer).” If the moral status of these chimeric animals is grounded in the phenomenal value of their interests—that is, their interests as nonhuman animals—current protections for animals used in research may be inadequate to protect those interests.
An advanced human error assessment approach: HEART and AV‐DEMATEL
Authors: Can Gülin F. , Delice Elif K.
Published: October 2019

Human error assessment and reduction technique (HEART) is one of the most commonly used human error assessment approaches which computes human error probability (HEP) to prioritize errors related to human actions. HEART is a powerful tool considering error producing conditions (EPCs) which increase the HEP for generalized task versions named as generic task types (GTTs). HEART can give a solution including prevention of human‐related errors (HREs) and reduction of the HREs’ impacts via implementing additional controls. However, it has many shortcomings for real‐life error assessments. In this context, this study aims to improve effective usage of HEART through an advanced version of decision‐making trial and evaluation laboratory (AV‐DEMATEL). The reason to perform AV‐DEMATEL is to show the complex effect relations between main tasks (MTs), subtasks (STs), and EPCs in a process. For this aim, an integrated effect relation matrix is proposed for DEMATEL and importance weights of MTs, STs, and EPCs are computed based on this matrix. In addition, not only HREs are considered but also machine‐related errors (MREs) are taken into account to make error assessment for the process. The proposed approach also provides flexibility to categorize STs in different GTTs. Finally, a new term “process error probability” including HREs’ probabilities and MREs’ probabilities is recommended to compute error probability in an integrated manner for the process. To utilize the proposed approach, an example of a steam boiler daily control process is given.
Ectopic osteogenesis by type I collagen loaded with a novel synthesized PTH‐related peptide‐1 in vivo
Authors: Wang Yi , Wang Jianping , Zheng Jin , Yu Mingxia , Cai Lin , Zhang Shuwei , Li Jingfeng
Published: October 2019

This study aims to investigate the ability of parathyroid hormone (PTH)‐related peptide‐1/type I collagen (PTHrP‐1/Col‐I) scaffold material to induce ectopic osteogenesis in the quadriceps muscle pocket of Sprague–Dawley (SD) rats. A novel peptide PTHrP‐1 was derived from PTH and used at different concentrations (0, 0.1, 0.3, and 0.5 mg/ml) to induce ectopic osteogenesis. Radiographic examinations (X‐ray, CT, and 3D reconstruction), pathological observations (H&E, Masson, Von Kossa, ALP and TRAP staining), immunohistochemical staining (Col‐I, OCN and Runx‐2 in tissues), western blotting was used to determine the qualitative and quantitative analysis of related markers proteins. Results confirmed that the appropriate concentration of PTHrP‐1 can effectively enhance the osteogenic activity, thereby improving the positive results and protein expression of osteogenic markers (COL‐I, OCN, and Runx‐2) in the quadriceps muscle pocket of SD rats. Through qualitative and quantitative analysis, high concentration of PTHrP‐1 promotes osteogenic activity and active bone resorption. This study confirmed that PTHrP‐1 is a novel small molecule bioactive peptide, and the rat tail collagen scaffold is a good carrier of PTHrP‐1 with excellent biocompatibility. The PTHrP‐1/Col‐I composite scaffold material is an effective substitute for bone tissue engineering and can effectively induce and promote bone formation in the quadriceps muscle pocket of rats. In addition, the promoting ability for osteogenic differentiation of 0.3 mg/ml PTHrP‐1/Col‐I composite scaffold material group was significantly better than that of 0, 0.1 and 0.5 mg/ml PTHrP‐1/Col‐I composite scaffold material groups. Hence, the optimal concentration of PTHrP‐1 to promote ectopic osteogenesis is 0.3 mg/ml.
Design and fabrication of clinoptilolite–nanohydroxyapatite/chitosan–gelatin composite scaffold and evaluation of its effects on bone tissue engineering
Authors: Sadeghinia Ali , Soltani Somaieh , Aghazadeh Marziyeh , Khalilifard Javad , Davaran Soodabeh
Published: October 2019

The aim of this study was to synthesize an innovative composite scaffold, which structured of clinoptilolite–nanohydroxyapatite/chitosan–gelatin (CLN–nHA/CS–G) with enhanced attributes for utilization in the bone tissue engineering. This composite scaffold was prepared by blending the CLN, nHA, chitosan, and gelatin solution followed by a freeze‐drying step. The fabricated composite scaffolds were studied using BET, FTIR, XRD, and SEM techniques. The highly porous composite scaffolds with a pore size of 200 ± 100 μm were synthesized. Moreover, the effects of CLN and nHA on the physicochemical features of the scaffold such as density, swelling ratio, biomineralization, biodegradation, and mechanical behavior were studied. Compared with CS–G scaffold, the presence of CLN and nHA leads to an increased surface area, increased biomineralization, and low rate of degradation in simulated body fluid solution (SBF) and mechanical strength. Cytotoxicity of the CLN–nHA/CS–G scaffold was studied by MTT assay on human dental pulp stem cells (h‐DPSCs). The biological response of h‐DPSCs showed no toxicity and studied cells proliferated and attached on the pore surfaces of the scaffold. Results indicated that introducing CLN and nHA to composite improves the scaffold characteristics in a way that makes it suitable for bone tissue engineering.
Nanofilm generated non‐pharmacological anabolic bone stimulus
Authors: Talukdar Yahfi , Rashkow Jason T. , Patel Sunny , Lalwani Gaurav , Bastidas Juan , Khan Slah , Sitharaman Balaji
Published: October 2019

Stimulus‐responsive nanomaterials have mainly been employed to ablate or destroy tissues or to facilitate controlled release of drugs or biologics. Herein, we demonstrate the potential of stimulus‐responsive nanomaterials to promote tissue regeneration via a non‐pharmacological and noninvasive strategy. Thin nanofilms of an optically‐absorbing organic dye or nanoparticle (single‐walled graphene nanoribbons [SWOGNR]) were placed over (without touching the skin) a rodent femoral fracture site. A nanosecond pulsed near‐infrared laser diode was employed to generate photoacoustic (PA) signals from the nanofilms. X‐ray micro‐computed tomography (microCT), histology, and mechanical testing results showed that daily PA stimulations of upto 45 min for 6 weeks (complete fracture healing) do not adversely affect bone regeneration and quality. Further, microCT and histological analysis showed 10 min daily stimulation for 2 weeks significantly increases bone quantity at the fracture sites of rats exposed to the nanoparticle‐generated PA signals. In these rats, up to threefold increase in bone volume to callus volume ratio and twofold increase in bone mineral density within the callus were noted, compared to rats that were not exposed to the photoacoustic signals. The results taken together indicate that nanofilm‐generated photoacoustic signals serve as an anabolic stimulus for bone regeneration. The results, in conjugation with the ability of these nanofilms to serve as PA contrast agents, present opportunities toward the development of integrated noninvasive imaging and noninvasive or invasive treatment strategies for bone loss due to disease or trauma.
Retracted: Upregulation of acetylcholinesterase caused by downregulation of microRNA‐132 is responsible for the development of dementia after ischemic stroke
Authors: Yang Fu‐wei , Wang Hao , Wang Chen , Chi Guo‐nan
Published: October 2019

MicroRNA‐132 (miR‐132) has been shown to participate in many diseases. This study aimed to understand the correlation between the level of miR‐132 and the severity of dementia post‐ischemic stroke. An online tool (www.mirdb.org) was used to find the miR‐132 binding site in acetylcholinesterase (ACHE) 3′‐untranslated region (UTR), followed by a luciferase reporter assay to validate ACHE as a miR‐132 target. A similar relationship between miR‐132 and ACHE was also established in cerebrospinal fluid samples collected from human subjects. A negative correlation was established between ACHE and miR‐132 by measuring the relative luciferase activity. Meanwhile, Western blot analysis and real‐time polymerase chain reaction were also conducted to compare the levels of ACHE messenger RNA and protein between two groups (dementia positive, n = 26 and dementia negative, n = 26) or among cells treated with miR‐132 mimics, ACHE small interfering RNA, and miR‐132 inhibitors. As shown in the results, miR‐132 can reduce the expression of ACHE. Further experiments were also carried out to study the effect of miR‐132 and ACHE on cell viability and apoptosis, and the results demonstrated that miR‐132 enhanced cell viability while suppressing apoptosis. In addition, ACHE reduced cell viability while promoting apoptosis. miR‐132 targeted ACHE and suppressed its expression. Additionally, miR‐132 and ACHE have been shown to affect the cell viability and apoptosis in the central nervous system.
miR‐205‐3p promotes proliferation and reduces apoptosis of breast cancer MCF‐7 cells and is associated with poor prognosis of breast cancer patients
Authors: Qiu Changhong , Huang Fei , Zhang Qing , Chen Wei , Zhang Huiting
Published: October 2019

Background

To study the expression of microribonucleic acid (miR)‐205 in breast cancer and its effects on the proliferation and apoptosis of breast cancer cells.

Methods

Breast cancer cell line MCF‐7 cells with stable expression of miR‐205‐3p were constructed. Cell proliferation, invasion, and apoptosis were detected via MTT assay, transwell assay, and flow cytometry, respectively. The expressions of Ezrin, LaminA/C, cleaved caspase‐3, Bcl‐2, and Bax were detected via Western blotting. The expressions of miR‐205‐3p in breast cancer tissues and para‐carcinoma tissues were detected via quantitative PCR (qPCR).

Results

In transfection group, cell proliferation and invasion capacities were increased significantly (P < 0.01), but apoptotic cells were significantly reduced (P < 0.01). In addition, the expressions of Ezrin, LaminA/C, and cleaved caspase‐3 in the transfection group were significantly decreased (P < 0.01), but the Bcl‐2/Bax ratio was significantly increased (P < 0.01). The miR‐205‐3p expression in tumor tissues of breast cancer patients was significantly higher than that in para‐carcinoma tissue, but Ezrin, LaminA/C, and cleaved caspase‐3 expressions in tumor tissues were remarkably declined (P < 0.01), while the Bcl‐2/Bax ratio was remarkably increased (P < 0.01). Moreover, the 5‐year survival of patients with high expression of miR‐205‐3p was significantly shorter than patients with normal or low expression (P < 0.01).

Conclusion

Highly expressed miR‐205‐3p can promote the proliferation and invasion and reduce the apoptosis of breast cancer cells, and the high expression of miR‐205‐3p can significantly reduce the survival time of patients.
Primary colonospheres maintain stem cell‐like key features after cryopreservation
Authors: Eini Leila , Naseri Marzieh , Karimi‐Busheri Feridoun , Bozorgmehr Mahmood , Ghods Roya , Madjd Zahra
Published: October 2019

The development of efﬁcient and repeatable protocols for biobanking and prolonged storage of cancer stem cells (CSCs), with minimum alterations in biological function, is valuable and desired, particularly for retrospective analysis and clinical applications. In particular, data regarding the effect of cryopreservation on CSCs's functional features is scarce. In this regard, few studies have been shown that 3D spheroid structures, which enriched for CSCs, can keep their biological phenotype and genetic profiles. Here, for the first time, we present data on cryopreservation of CT‐26 colonospheres, with the focus on essential stem cell‐like properties after thawing. Tumor biopsy‐derived colonospheres were frozen in standard freezing media (90% fetal bovine serum + 10% dimethyl sulfoxide) and stored in liquid nitrogen for 10 months. Then, cryopreservation effect on preservation of CSCs‐related features was verified using real‐time polymerase chain reaction for evaluation of stemness genes and flow cytometry for the putative colorectal CSC surface biomarkers. The self‐renewal capacity of thawed spheres was also compared with their fresh counterparts using serial formation assay. Finally, tumorigenic capacity of both groups was evaluated in immunocompetence mouse model. Our data indicated that postthawed colonospheres had high viability without drastic alteration in biological and structural features and maintained self‐renewal potential after sequential passages. Real‐time analysis showed that both fresh and frozen colonospheres displayed similar expression pattern for key stemness genes: SOX2 and OCT4. Cryopreserved spheroids expressed CD133, CD166, and DCLK1 CSCs surface biomarkers at elevated levels when compared with parental as non‐cryopreserved counterparts. Our electron scanning microscopy micrographs clearly demonstrated that postthawed colonospheres retain their integrity and cell surface morphology and characteristics. We also found that both fresh and frozen spheroids were equally tumorigenic. This study represented an effective strategy for reliable storage of intact CT‐26 colonospheres; this can provide researchers with a functionally reliable repository of murine colorectal CSCs for their future CSCs projects.
Comparative evaluation of two immunoassays for serological diagnosis of hepatitis E
Authors: Sampedro Antonio , Casanovas Isabel , Ceballos Julian , Rodriguez‐Granger Javier , Cobo Fernando , Navarro Jose Maria
Published: October 2019

Serological testing for immunoglobulin M (IgM) antibodies to Hepatitis E virus (HEV) is useful for diagnosing acute hepatitis E. Our aim was to evaluate the performance of chemiluminescence immunoassay (HEV IgM; Vircell, Granada, Spain) in comparison with a manual enzyme immunoassay (Anti‐HEV virus; Wantai, Beijing, China) for anti‐HEV IgM detection. Seventeen HEV‐RNA positive and 69 HEV‐RNA negative sera were tested by both assays. Virclia sensitivity was 94.1%, whereas that of the enzyme immunosorbent assay (EIA) was 76.5%; specificity was 98.5% and 97.1% for Virclia and EIA, respectively. Differences between both assays were not statistically significant. Virclia HEV IgM showed excellent performance and can be a good alternative to conventional enzyme immunoassays for the detection of IgM against HEV.
Meltwater discharge during the Holocene from the Wilkes subglacial basin revealed by beryllium isotope analysis of marine sediments
Authors: Behrens Bethany , Miyairi Yosuke , Sproson Adam D. , Yamane Masako , Yokoyama Yusuke
Published: October 2019

Understanding Antarctic Ice Sheet dynamics related to global climate change is of scientific and societal interest as the future behaviour of the ice sheet under the currently changing climate is unknown. We present beryllium‐10 (10Be) analysis of a high‐resolution marine sediment core from the Adélie Basin near the eastern Wilkes Land margin, which is susceptible to marine ice sheet instability due to the low‐lying nature and down‐sloping trough of the Wilkes Subglacial Basin. Combined with a newly constructed age model using compound specific radiocarbon dates, the data reveal three events associated with high meteoric 10Be at ca. ~10 ka, ca. ~6.5 ka and from ca. ~4 ka. We interpret these high meteoric 10Be events to be derived from the deposition of 10Be released from the ice sheet during meltwater discharge. In particular, the shift to higher meteoric 10Be concentration at~4 ka may correspond to changes in climate patterns at this time. Copyright © 2019 John Wiley & Sons, Ltd.
Recurrence risk evaluation in T1N1M0/T2N0M0/T3N0M0 gastric cancer with TP53 codon 72 polymorphisms
Authors: Ohmori Yukimi , Nomura Takashi , Fukushima Norimasa , Takahashi Fumiaki , Iwaya Takeshi , Koeda Keisuke , Nishizuka Satoshi S. ,   Members of the Northern Japan Gastric Cancer Study Consortium
Published: October 2019

Background

Postoperative adjuvant chemotherapy is not indicated for T1N1M0/T2N0M0/T3N0M0 gastric cancer. However, approximately 10% to 30% of these patients experience recurrence and metastasis.

Methods

Among 658 patients with gastric cancer who received gastrectomy with curative intent, 130 T1N1M0/T2N0M0 and 73 T3N0M0 patients were enrolled. Overall survival (OS) and relapse‐free survival (RFS) were analyzed based on TP53 codon 72 polymorphisms Arg/Arg, Arg/Pro, and Pro/Pro. The hazard ratio (HR) for each subgroup was compared by TP53 codon 72 polymorphisms.

Results

Of the 189 patients for whom polymorphism analysis results were available, the 5‐ and 10‐year OS was 84.9% and 65.1%, respectively. The 5‐ and 10‐year RFS was 81.8% and 65.4%, respectively. When the study cohort was divided into two groups according to polymorphism status (ie, “Arg/Arg and Arg/Pro” vs Pro/Pro), both the OS (HR, 2.799; 95% confidence interval [CI], 1.071‐7.315; P = .036) and RFS (HR, 2.639; 95% CI, 1.025‐6.794; P = .044) of the Pro/Pro group were significantly lower than those for the Arg/Arg and Arg/Pro groups across the entire observation period.

Conclusions

The TP53 codon 72 Pro/Pro polymorphism may isolate a relatively high‐risk patient group in T1N1M0/T2N0M0/T3N0M0 gastric cancer.
The role of preoperative albumin‐bilirubin grade for oncological risk stratification in liver transplant patients with hepatocellular carcinoma
Authors: Kornberg Arno , Witt Ulrike , Schernhammer Martina , Kornberg Jennifer , Müller Katharina , Friess Helmut , Thrum Katharina
Published: October 2019

Background and Objectives

Albumin‐bilirubin (ALBI) score was shown to correlate with liver function and tumor recurrence after hepatectomy for hepatocellular carcinoma (HCC). The aim of this study was to assess the prognostic value of ALBI grade in liver transplantation (LT) patients with HCC.

Methods

Pre‐LT available independent predictors of recurrence‐free survival (RFS) and microvascular tumor invasion (MVI) were determined in 123 patients with HCC.

Results

Posttransplant HCC recurrence rates were 10.5%, 15.9%, and 68.2% in ALBI grade 1, 2, and 3, respectively (P < .001). Along with serum α‐fetoprotein (AFP) and C‐reactive protein (CRP) levels, ALBI grades 1 or 2 was identified as an independent predictor of RFS (hazard ratio, 3.52; 95% confidence interval [CI], 1.577‐7.842; P = .002). Furthermore, ALBI grade 3 proved to be the strongest indicator of MVI (odds ratio, 11.59; 95% CI, 3.412‐39.381; P < .001). A novel oncological risk score‐based on AFP, CRP, and ALBI grade provided the best discriminative capacity (c‐statistic 0.806) in selecting liver recipients with low oncological risk profile.

Conclusion

Preoperative ALBI grade seems to be valuable for refinement of oncological risk stratification at LT for HCC.
Marine heat waves, climate change, and failed spawning by coastal invertebrates
Authors: Shanks Alan L. , Rasmuson Leif K. , Valley Jenna R. , Jarvis Marley A. , Salant Carly , Sutherland David A. , Lamont Eleanor I. , Hainey MacKenna A. H. , Emlet Richard B.
Published: October 2019

To investigate the timing and intensity of winter spawning by coastal invertebrates, we enumerated embryos in plankton samples collected in daily time series from January to March of 2014 (79 d), 2015 (73 d), and 2016 (74 d). Samples were collected near the mouth of the Coos Bay estuary in Oregon. We enumerated several hundred different morphologically distinct types of embryos and larvae representing at least five phyla. Forty‐three embryo types were abundant enough (abundance > 500 over the time series) to enable statistical analysis. Twenty of these types were identified using genetic barcoding of which there were four nemerteans, four gastropods, four chitons, five polychaetes, and two echinoderms. In winter 2014, hydrographic conditions were similar to average historical values. Conditions in 2015 and 2016 were characterized by marine heat waves (MHWs). In 2015, the “warm blob”—anomalously warm water in the Northeastern Pacific—affected conditions and in 2016, there was a strong El Niño. In 2015 and 2016, winter spawning intensity was orders of magnitude lower than in 2014 and many taxa failed to spawn (11 and 24 in 2015 and 2016, respectively); spawning appears to have been adversely impacted by the MHWs. The MHW of 2015 has been attributed to anthropogenic global climate change while the 2016 El Niño may have been strengthened by climate change. The frequency, intensity, and duration of MHW are projected to increase dramatically with global warming, which may adversely affect reproduction and recruitment by numerous marine taxa.
Evaluation of Safety and Efficacy of Laser Hair Removal With the Long‐Pulsed 755 nm Wavelength Laser: A Two‐Center Study With 948 Patients
Authors: Russe Elisabeth , Purschke Martin , Herold Manfred , Sakamoto Fernanda H. , Wechselberger Gottfried , Russe‐Wilflingseder Katharina
Published: October 2019

Background and Objectives

Laser hair removal is the most common laser therapy and the third most commonly performed procedure with more than one million treatments in United States in 2016. This retrospective study was conducted to assess long‐term efficacy and safety of the 755 nm laser for hair removal.

Study Design/Materials and Methods

Nearly, 3,606 laser treatments were performed with the long‐pulsed 755 nm wavelength laser equipped with an epidermal cooling device between 1997 and 2005 and were followed till 2013. Standardized assessments were conducted by two treating physicians and patients at two follow‐up intervals. At first follow‐up, clearance was assessed by two physicians and clearance and satisfaction by patients. At the second follow‐up, patients were assessed if hair clearance sustained compared with the first follow‐up.

Results

Nine hundred and forty‐eight patients with Fitzpatrick skin types I–IV were treated with a total of 3,606 laser treatments in this study. The mean age at the beginning of the study was 35 years (±11), 95.1% of patients were female (n = 902) and 4.9% male (n = 46). Five hundred and seventy‐four patients received a minimum of three treatments and an average of 5.31 (3–16) treatments on axilla, back, bikini, breast, abdomen, face, lower extremity, or upper extremity region. First, follow‐up was conducted 3.9 (±1.5) years after the final laser treatment. Seventy‐four percent of these patients received 75–100% clearance as reported by the physician and 48% clearance as reported by the patient. Fifty‐two percent of patients reported slower hair growth and 42% change in hair texture. Ninety percent of patients treated on axilla, 82% treated on the bikini area, and 79% treated on lower extremities experienced 75% or more clearance after three treatments. Facial, as well as breast and abdomen treatments, only showed a 66% and 62%, respectively, after three treatments. For these locations, five and more treatments were needed to achieve a quote of 79% (face) or 80% (breast and abdomen) for a 75–100% clearance. Upper extremity and back treatments did not have enough physician ratings to draw conclusions. Long‐term adverse events were minimal and were all located on the face (one patient scar, four patients herpes infection). Second follow‐up of 173 patients was conducted after 11.5 years (±2.0) and 87.9% of patients reported that their improvement sustained.

Conclusions

The long‐pulsed 755 nm alexandrite laser is a safe and efficacious treatment for the reduction of unwanted body hair with permanent results and high patient satisfaction. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
Evaluation of suitable reference genes for normalization of quantitative reverse transcription PCR analyses in Clavibacter michiganensis
Authors: Jiang Na , Lyu Qingyang , Han Sining , Xu Xin , Walcott Ronald R. , Li Jianqiang , Luo Laixin
Published: October 2019

Clavibacter michiganensis, the causal agent of bacterial canker of tomato, is a Gram‐positive bacterium and a model for studying plant diseases. The real‐time quantitative reverse transcription PCR (real‐time qRT‐PCR) assay is widely used to quantify gene expression in plant pathogenic bacteria. However, accurate quantification of gene expression requires stably expressed reference genes that are consistently expressed during the experimental conditions of interest. The use of inappropriate reference genes leads to a misinterpretation of gene expression data and false conclusions. In current study, we empirically assessed the expression stability of six housekeeping genes (gyrB, rpoB, tufA, bipA, gapA, and pbpA) of C. michiganensis under five experimental conditions using two algorithms, geNorm and NormFinder. C. michiganensis expressed gyrB, bipA, and gapA stably when growing in nutrient‐rich broth (TBY broth and modified M9 broth). We concluded that pbpA, tufA, and gyrB were suitable reference genes in C. michiganensis—tomato interaction studies. We also recommended bipA and rpoB to be used to study bacterial gene expression under nutrient‐poor conditions. Finally, gyrB, pbpA, and rpoB can be used to normalize the quantification of C. michiganensis gene expression while the bacterium is in the viable but nonculturable (VBNC) state. This study identified the most suitable reference genes depending on the experimental conditions for calibrating real‐time qRT‐PCR analyses of C. michiganensis and will be useful in studies that seek to understand the molecular interactions between C. michiganensis and tomato.
Role of putrescine in ovary and embryo development in fruit bat Cynopterus sphinx during embryonic diapause
Authors: Anuradha  , Banerjee Arnab , Krishna Amitabh
Published: October 2019

The aim of this study was to evaluate the effect of putrescine on ovarian activity and the rate of embryonic development in Cynopterus sphinx during delayed development. The result showed the presence of a rate‐limiting enzyme, ornithine decarboxylase‐1, in both ovary and utero‐embryonic unit of C. sphinx suggests a synthesis of putrescine in these sites. The corpus luteum showed increased, whereas utero‐embryonic unit showed decreased production of putrescine during delayed development as compared with the normal development. The bat treated in vivo with putrescine during delayed development showed increase in progesterone and estradiol synthesis, correlated with increased expression of luteinizing hormone receptor, steroidogenic acute receptor protein, and 3β‐hydroxysteroid dehydrogenase through extracellular signal‐regulated kinase (ERK1/2)‐mediated pathway in the ovary; but showed increase in the weight and expression of progesterone receptor (PR), B‐cell lymphoma 2, proliferating cell nucleus antigen, and vascular endothelial growth factor proteins in utero‐embryonic unit. The in vitro treatment of putrescine showed stimulatory whereas treatment with an inhibitor of putrescine, 2‐difluoromethylornithine caused an inhibitory effect on ovarian progesterone synthesis and cell proliferation, and cell survival in the utero‐embryonic unit. In conclusion, the putrescine showed two separate roles during embryonic diapause, high concentration of putrescine in the ovary may support corpus luteum and basal synthesis of progesterone, whereas a low level of putrescine causes retarded embryonic development by inhibiting cell proliferation in the utero‐embryonic unit. The bat treated with putrescine either directly promotes cell proliferation, cell survival, and angiogenic activities or acts indirectly increasing PR on utero‐embryonic unit thereby activating development in delayed embryo in C. sphinx.
Does asymptomatic bacteriuria increase the risk of adverse events or modify the efficacy of intradetrusor onabotulinumtoxinA injections?
Authors: Aharony Shachar , Przydacz Mikolaj , Van Ba Ornella L. , Corcos Jacques
Published: October 2019

Aim

To assess the impact of asymptomatic bacteriuria (ASB) on the safety and efficacy of intradetrusor onabotulinumtoxinA injections in patients with overactive bladder and neurogenic detrusor overactivity.

Methods

We reviewed the medical records of patients who had received onabotulinumtoxinA between 2009 and 2014. Safety analysis was based on the appearance of urinary tract infections (UTIs), hematuria, and need for hospitalization because of related adverse event(s) in the month after injection. Patients who underwent urodynamic study before and 3 months after the first onabotulinumtoxinA treatment were included in efficacy analysis. Changes in maximal cystometric capacity (MCC), bladder compliance (BC), maximal detrusor pressure at maximal involuntary detrusor contraction (Pdetmax), and detrusor leak point pressure (DLPP) were assessed.

Results

Totally, 183 patients underwent 457 injection sessions. ASB was found in 38.8% (185) of urine cultures taken before injections. After treatment, 49 patients (with or without ASB) developed UTI. Urosepsis did not occur. The odds ratio of UTI in patients with ASB was 16.48. The efficacy cohort, consisting of 83 patients, showed that ASB had no significant effect on any of the efficacy parameters (MCC‐risk ratio [RR]: 0.93, 95% confidence interval [CI]: 0.72‐1.21; BC‐RR: 0.88, 95% CI: 0.62‐1.24; Pdetmax‐RR: 0.9, 95% CI: 0.69‐1.21; DLPP‐RR: 1.69, 95% CI: 0.72‐3.97).

Conclusions

ASB is common among patients who are candidates for intradetrusor onabotulinumtoxinA treatment. ASB increases the risk of UTI, but does not heighten the risk of urosepsis, hospitalization, or therapy failure. This study should lead to the reconsideration of current recommendations.
Reasons for cessation of clean intermittent catheterization after spinal cord injury: Results from the Neurogenic Bladder Research Group spinal cord injury registry
Authors: Patel Darshan P. , Herrick Jennifer S. , Stoffel John T. , Elliott Sean P. , Lenherr Sara M. , Presson Angela P. , Welk Blayne , Jha Amitabh , Myers Jeremy B. ,   for the Neurogenic Bladder Research Group (NBRG.org)
Published: October 2019

Introduction

Clean intermittent catheterization (CIC) is recommended for bladder management after spinal cord injury (SCI) since it has the lowest complication rate. However, transitions from CIC to other less optimal strategies, such as indwelling catheters (IDCs) are common. In individuals with SCI who stopped CIC, we sought to determine how individual characteristics affect the bladder‐related quality of life (QoL) and the reasons for CIC cessation.

Methods

The Neurogenic Bladder Research Group registry is an observational study, evaluating neurogenic bladder‐related QoL after SCI. From 1479 participants, those using IDC or urinary conduit were asked if they had ever performed CIC, for how long, and why they stopped CIC. Multivariable regression, among participants discontinuing CIC, established associations between demographics, injury characteristics, and SCI complications with bladder‐related QoL.

Results

There were 176 participants who had discontinued CIC; 66 (38%) were paraplegic and 110 (63%) were male. The most common reasons for CIC cessation among all participants were inconvenience, urinary leakage, and too many urine infections. Paraplegic participants who discontinued CIC had higher mean age, better fine motor scores, and lower educational attainment and employment. Multivariable regression revealed years since SCI was associated with worse bladder symptoms (neurogenic bladder symptom score), ≥4 urinary tract infections (UTIs) in a year was associated with worse satisfaction and feelings about bladder symptoms (SCI‐QoL difficulties), while tetraplegia was associated better satisfaction and feelings about bladder symptoms (SCI‐QoL difficulties).

Conclusions

Tetraplegics who have discontinued CIC have an improved QoL compared with paraplegics. SCI individuals who have discontinued CIC and have recurrent UTIs have worse QoL.
Add‐on effects of tadalafil in tamsulosin‐treated patients with small benign prostatic enlargement: A randomized, placebo‐controlled, double‐blind, crossover study
Authors: Negoro Hiromitsu , Goto Takayuki , Akamatsu Shusuke , Terada Naoki , Kobayashi Takashi , Matsui Yoshiyuki , Yamamoto Takashi , Omura Tomohiro , Yonezawa Atsushi , Matsubara Kazuo , Ogawa Osamu
Published: October 2019

Aim

To assess the add‐on effects of tadalafil in patients with a relatively small benign prostatic enlargement (BPE) treated with tamsulosin.

Methods

From September 2014 to July 2018, we prospectively studied patients (aged 50 years or more) attending our hospital who had received tamsulosin for small BPE (20–40 mL) for 4 weeks at least and still had residual lower urinary tract symptoms (LUTS) with total International Prostate Symptom Scores (IPSS) of at least 8 and IPSS‐quality of life scores at least 3. We randomized eligible patients into two groups: one of which received tadalafil 5 mg once daily for 6 weeks, followed by placebo for 6 weeks, and the other of which received placebo followed by tadalafil in the same manner. The patients were reviewed at our outpatient clinic after 2, 6, 8, and 12 weeks.

Results

There were 13 patients in the tadalafil‐placebo and 13 in the placebo‐tadalafil group. Their median ages (range) were 70 (65‐85) and 73 (50‐80) years, prostatic volumes (median) 30.0 (22.0‐39.7) and 32.0 (20.1‐39.5) mL, and total IPSS (median) 17 (10‐27) and 16 (10‐24), respectively. The primary endpoints, namely mean changes of total IPSS from baseline, were 1.85 on placebo and −3.42 on tadalafil; this difference is statistically significant (difference: −1.57; 95% confidence interval: −3.00, −0.69; P = .032). We encountered no adverse effects.

Conclusions

Add‐on of tadalafil for symptomatic patients with small BPE treated with tamsulosin appears to be effective and safe.
A Novel, Non‐opioid Treatment for Chronic Pelvic Pain in Women with Previously Treated Endometriosis Utilizing Pelvic‐Floor Musculature Trigger‐Point Injections and Peripheral Nerve Hydrodissection
Authors: Plavnik Kathy , Tenaglia Amy , Hill Charity , Ahmed Tayyaba , Shrikhande Allyson
Published: October 2019

Background

Endometriosis is the abnormal growth of uterine tissue outside the uterine cavity that can cause chronic pain, dysmenorrhea, and dyspareunia. Although the disease is common and nonmalignant in nature, the symptoms can severely impact function and quality of life. Treatment options for endometriosis are limited and not well understood despite a growing need.

Objective

To determine the effectiveness of pelvic‐floor musculature trigger‐point injections and peripheral nerve hydrodissection in treating endometriosis symptoms, associated pain, and pelvic functionality.

Design

Retrospective longitudinal study case series.

Setting

Private practice.

Patients

Sixteen female patients with biopsy‐confirmed endometriosis.

Interventions

Ultrasound‐guided pelvic‐floor trigger‐point injections and peripheral nerve hydrodissection performed once a week for 6 weeks.

Main Outcome Measurements

Pelvic pain intensity as measured pretreatment and posttreatment by the 0 to 10 Visual Analogue Scale (VAS) and the Functional Pelvic Pain Scale (FPPS).

Results

Pretreatment, the mean VAS score was 6.0 (standard deviation [SD] 2.7), and posttreatment the mean VAS score was 2.9 (SD 2.6); P < .05, 95% confidence interval (CI) 1.16 to 4.97. The mean total FPPS score before treatment was 14.4 (SD 5.2) and posttreatment it was 9.1 (SD 5.8); P < .05, 95% CI 1.34 to 9.28. Analysis of the subcategories within the FPPS indicated that the improvement was statistically significant in the categories of intercourse, sleeping, and working. In the category of intercourse, the mean change in score after treatment was 1.3 (P < .05, 95% CI 0.26‐2.31). In the category of sleeping, the mean change in score after treatment was 1.2 (P < .05, 95% CI 0.32‐1.99). In the category of working, the mean change in score after treatment was 0.9 (P < .05, 95% CI 0.18‐1.53).

Conclusions

Analysis suggests that the treatment was effective at relieving pain related to endometriosis; it also reflected promise in improving overall pelvic function, particularly in relation to intercourse, working, and sleeping.
The value of tumor markers in men with metastatic prostate cancer undergoing [177Lu]Lu‐PSMA therapy
Authors: Yordanova Anna , Linden Paula , Hauser Stefan , Feldmann Georg , Brossart Peter , Fimmers Rolf , Essler Markus , Holdenrieder Stefan , Ahmadzadehfar Hojjat
Published: October 2019

Background

Currently, prostate‐specific membrane antigen‐radioligand therapy (PSMA‐RLT) is considered a last‐line treatment option in advanced castration‐resistant prostate cancer. Despite these patients' poor prognosis, accurate estimation of their overall survival (OS) is essential to determine whether benefits exist from the treatment and whether the loss of valuable time and unnecessary side effects can be avoided. The aim of the present study is to evaluate whether various biochemical markers can predict OS in men undergoing PSMA‐RLT and whether the changes assessed after PSMA‐RLT correlate with the OS.

Methods

The tested tumor markers in this retrospective analysis were alkaline phosphatase (ALP), bone‐specific alkaline phosphatase (BAP), prostate‐specific antigen (PSA), lactate dehydrogenase (LDH), chromogranin A, and pro‐gastrin‐releasing peptide (pro‐GRP). For the evaluation, we performed blood tests before each PSMA‐RLT cycle and during follow‐up visits (which were 2‐3 months apart). All patients were followed up until their deaths. To test the correlations between the tumor markers and survival, we conducted the logrank tests and the multivariate Cox proportional‐hazards regression model. The significance level was set at P < .05.

Results

The study included 137 patients who received a total of 487 PSMA‐RLT cycles between January 2015 and November 2017. Of the tested biochemical tumor markers, baseline ALP (120 U/L cut‐off), LDH (248 U/L cut‐off), and PSA (first quartile cut‐off) correlated significantly with survival post‐PSMA‐RLT (P < .001 for ALP and LDH, and P = .007 for PSA). Stable and/or decreased values in most of the initially abnormal parameters were associated with significantly better OS; these parameters were ALP (P = .009), LDH (P = .005), PSA (P < .001), and pro‐GRP (P = .013). The BAP and ALP responses also correlated significantly with survival in patients with bone metastases (P = .002 and P < .001, respectively). Furthermore, there was a strong correlation of the kinetic patterns of PSA, ALP, BAP, and LDH with the survival, showing that patients with steadily increasing markers had the shortest OS.

Conclusion

Along with the established tumor marker PSA, ALP, LDH, BAP, and pro‐GRP were correlated with the OS post‐PSMA‐RLT in the univariate and multivariate analyses.
What are the statistical implications of treatment non‐compliance in cluster randomized trials: A simulation study
Authors: Moerbeek Mirjam , Schie Sander van
Published: October 2019

Subjects in randomized controlled trials do not always comply to the treatment condition they have been assigned to. This may cause the estimated effect of the intervention to be biased and also affect efficiency, coverage of confidence intervals, and statistical power. In cluster randomized trials non‐compliance may occur at the subject level but also at the cluster level. In the latter case, all subjects within the same cluster have the same compliance status. The purpose of this study is to investigate the statistical implications of non‐compliance in cluster randomized trials. A simulation study was conducted with varying degrees of non‐compliance at either the cluster level or subject level. The probability of non‐compliance depends on a covariate at the cluster or subject level. Various realistic values of the intraclass correlation coefficient and cluster size are used. The data are analyzed by intention to treat, as treated, per protocol and the instrumental variable approach. The results show non‐compliance may result in downward biased estimates of the intervention effect and an under‐ or overestimate of its standard deviation. The coverage of the confidence intervals may be too small, and in most cases, empirical power is too small. The results are more severe when the probability of non‐compliance increases and the covariate that affects compliance is unobserved. It is advocated to avoid non‐compliance. If this is not possible, compliance status and covariates that affect compliance should be measured and included in the statistical model.
Analysis of longitudinal adherence data: Hitting the target with consistency
Authors: Watson David , Nickel Amanda
Published: October 2019

Typical descriptions of partial adherence summarize to what extent a patient follows a prescribed treatment plan. Another aspect of adherence relates to how consistently a patient behaves. We distinguish these two notions as “adherence target” and “adherence consistency.” Most research on adherence focuses on the former concept, but the latter can be a useful idea in assessing patients' compliance. Quantifying these two notions goes beyond typical summaries of center and spread, because they may be related to each other. That is, the mean is often related to the standard deviation via the variance function. Our approach defines a parameter that measures consistency separate from the adherence target. For exponential dispersion or quasi‐likelihood families, the parameter corresponds to the dispersion parameter. Assessing adherence consistency to medical treatment requires longitudinal data, which can be collected with new technology. Two examples from pediatric medicine demonstrate that detangling the notion of consistency from the adherence target is useful.