bluuebunny/crossref_metadata_2025_split huggingface dataset:
Opioid therapy duration before naldemedine treatment is a significant independent risk of diarrhea: a retrospective cohort study
Authors: Okamoto Akiharu , Ikemura Kenji , Mizutani Eri , Iwamoto Takuya , Okuda Masahiro 
Published: February 2021

Abstract
Background
The most common adverse event (AE) associated with opioid analgesics is opioid-induced constipation (OIC). Naldemedine (NAL) is widely used for the treatment of OIC. However, diarrhea has been reported as the most common treatment-emergent AE of NAL, and little is known about the risk factors associated with the development of diarrhea during NAL administration. This study examined the risk factors for NAL-induced diarrhea via a retrospective chart review of hospitalized patients.

Methods
The data of 101 hospitalized adult patients who received NAL for the first time for the treatment of OIC at Mie University Hospital between June 2017 and December 2018 were extracted from electronic medical records. According to the inclusion and exclusion criteria, 70 of the 101 patients were enrolled in this study. Diarrhea was defined as “diarrhea” on the medical record within 2 weeks of NAL administration. Univariate and multivariate analyses were performed to identify risk factors for the development of diarrhea in patients receiving NAL.

Results
Twenty-two of the 70 patients enrolled (31%) developed diarrhea within 2 weeks of NAL administration. The median duration (range) of NAL treatment before diarrhea onset was 3 (1–12) days. Patients with diarrhea had a significantly longer duration of opioid therapy before NAL administration than patients without diarrhea (P=0.002). Multivariate logistic regression analysis indicated that the independent risk factors for the development of NAL-induced diarrhea were NAL administration after more than 17 days of opioid therapy (odds ratio [OR]=7.539; P=0.016) and pancreatic cancer (OR=6.217; P=0.025). In fact, the incidence of diarrhea in patients who were administered NAL within a day of opioid therapy was significantly lower than that in patients who were administered NAL after more than 17 days of opioid therapy (13% vs. 54%, P=0.030).

Conclusions
These results suggested that a prolonged duration of opioid therapy prior to NAL initiation is associated with increased incidence of diarrhea.
Pharmacist-physician collaborative care for outpatients with left ventricular assist devices using a cloud-based home medical management information-sharing system: a case report
Authors: Katada Yoshiki , Yonezawa Atsushi , Utsumi Momoe , Kitada Noriaki , Sato Yu-ki , Matsumura Katsuyuki , Sukeishi Asami , Nakagawa Shunsaku , Imai Satoshi , Nakagawa Takayuki , Minakata Kenji , Kanemitsu Hideo , Minatoya Kenji , Nomoto Shinichi , Matsubara Kazuo 
Published: February 2021

Abstract
Background
The standard anticoagulation therapy for patients implanted with left ventricular assist devices (LVADs) includes warfarin therapy. We developed a cloud-based home medical management information-sharing system named as LVAD@home. The LVAD@home system is an application designed to be used on iPad tablet computers. This system enables the sharing of daily information between a patient and care providers in real time. In this study, we reported cases of outpatients with LVADs using this system to manage anticoagulation therapy.

Case presentation
The patient, a man in his 40s with end-stage heart failure owing to non-ischemic dilated cardiomyopathy, underwent LVAD implantation and warfarin was started on postoperative day 1. He started to use LVAD@home to manage warfarin therapy after discharge (postoperative day 47). He sent his data to care providers daily. By using this system, the pharmacist observed his signs of reduced dietary intake 179 days after discharge, and after consulting the physician, told the patient to change the timing of the next measurement earlier than usual. On the next day, the prothrombin time-international normalized ratio increased from 2.0 to 3.0, and thus the dose was decreased by 0.5 mg. Four patients used this system to monitor warfarin therapy from October 2015 to March 2018. In these patients, the time in therapeutic range was 90.1 ± 1.3, which was higher than that observed in previous studies. Additionally, there were no thromboembolic events or bleeding events.

Conclusions
The cloud-based home management system can be applied to share real-time patient information of factors, including dietary intake that interact with warfarin. It can help to improve long-term anticoagulation outcomes in patients implanted with LVAD.
Study protocol: a pilot quasi-experimental trial of tele-rehabilitation and tele-drain care post-mastectomy
Authors: Asano Miho , Koh Gerald Choon-Huat , Madhukumar Preetha , Teng Gladys Yu Hui , Liew Petrina Li Ling , Nagalingam Saraswathi , Tan May Leng Mabel , Ng Yee Sien , Tan Benita Kiat Tee 
Published: February 2021

AbstractBackgroundBreast cancer is the leading cancer affecting women in Singapore. Its survivors commonly experience decline in physical function and quality of life post-mastectomy, due to their upper limb morbidity and wound issues. Rehabilitation can address the aforementioned issues. When rehabilitation is accessible and easy to adhere, it can optimize recovery.Home-based tele-rehabilitation guided by healthcare professionals and self-managed by patients can potentially optimize the patients’ adherence to rehabilitation and recovery. With that in mind, a team of breast cancer specialists (oncologists, nurses, and therapists) in Singapore has developed one of the first tele-rehabilitation systems for local women undergoing a unilateral mastectomy. To our knowledge, no such systems have been evaluated or proven effective as a treatment option among local breast cancer patients with acute disabilities.MethodsThis is a pilot quasi-experimental trial that aims to evaluate the feasibility of tele-rehabilitation and tele-drain care compared to usual care. Up to 40 patients (20 per group) will be recruited for this trial. They will be assigned to an intervention group that receives rehabilitation via a tele-rehabilitation system or a control group that receives rehabilitation in person at their clinic. The primary outcome of this trial is rehabilitation participation (i.e., the time spent on rehabilitation). The secondary outcomes are upper extremity functioning, perceived health, and quality of life.DiscussionAs part of this pilot trial, patients who opt in for the tele-rehabilitation will be asked to share their experience with and thoughts on the tele-rehabilitation system. With the evidence obtained from the tele-rehabilitation patients of this trial, we will be able to improve the current system for our future trial. Further, our additional data on rehabilitation participation, physical function, and quality of life will help us design a sufficiently powered future main trial.Trial registrationThe trial was approved by the National Healthcare Group’s Domain Specific Review Board (#2019/00283) and registered withwww.ClinicalTrials.gov(#NCT04269967) in February 2020.
Application of a simplified Grey Wolf optimization technique for adaptive fuzzy PID controller design for frequency regulation of a distributed power generation system
Authors: Padhy Sasmita , Panda Sidhartha 
Published: February 2021

AbstractA Simplified Grey Wolf Optimizer (SGWO) is suggested for resolving optimization tasks. The simplification in the original Grey Wolf Optimizer (GWO) method is introduced by ignoring the worst category wolves while giving priority to the better wolves during the search process. The advantage of the presented SGWO over GWO is a better solution taking less execution time and is demonstrated by taking unimodal, multimodal, and fixed dimension test functions. The results are also contrasted to the Gravitational Search Algorithm, the Particle Swarm Optimization, and the Sine Cosine Algorithm and this shows the superiority of the proposed SGWO technique. Practical application in a Distributed Power Generation System (DPGS) with energy storage is then considered by designing an Adaptive Fuzzy PID (AFPID) controller using the suggested SGWO method for frequency control. The DPGS contains renewable generation such as photovoltaic, wind, and storage elements such as battery and flywheel, in addition to plug-in electric vehicles. It is demonstrated that the SGWO method is superior to the GWO method in the optimal controller design task. It is also seen that SGWO based AFPID controller is highly efficacious in regulating the frequency compared to the standard PID controller. A sensitivity study is also performed to examine the impact of the unpredictability in the parameters of the investigated system on system performance. Finally, the novelty of the paper is demonstrated by comparing with the existing publications in an extensively used two-area test system.
A dynamic and mosaic basement membrane controls cell intercalation in Drosophila ovaries
Authors: Van De Bor Véronique , Loreau Vincent , Malbouyres Marilyne , Cerezo Delphine , Placenti Audrey , Ruggiero Florence , Noselli Stéphane 
Published: February 2021

ABSTRACT
Basement membranes (BM) are extracellular matrices assembled into complex and highly organized networks essential for organ morphogenesis and function. However, little is known about the tissue origin of BM components and their dynamics in vivo. Here, we unravel the assembly and role of the BM main component, Collagen type IV (ColIV), in Drosophila ovarian stalk morphogenesis. Stalks are short strings of cells assembled through cell intercalation that link adjacent follicles and maintain ovarian integrity. We show that stalk ColIV has multiple origins and is assembled following a regulated pattern leading to a unique BM organisation. Absence of ColIV leads to follicle fusion, as observed upon ablation of stalk cells. ColIV and integrins are both required to trigger cell intercalation and maintain mechanically strong cell-cell attachment within the stalk. These results show how the dynamic assembly of a mosaic BM controls complex tissue morphogenesis and integrity.
Characterization of human bone marrow niches with metabolome and transcriptome profiling
Authors: Ayhan Selda , Nemutlu Emirhan , Uçkan Çetinkaya Duygu , Kır Sedef , Özgül Rıza Köksal 
Published: February 2021

ABSTRACT
Bone marrow (BM) niches are special microenvironments that work in harmony with each other for the regulation and maintenance of hematopoiesis. Niche investigations have thus far been limited to various model organisms and animal studies; therefore, little is known about different niches in healthy humans. In this study, a special harvesting method for the collection of BM from two different anatomical regions in the iliac crest of humans was used to investigate the presence of different niches in BM. Additionally, metabolomic and transcriptomic profiles were compiled using comparative ‘omics’ technologies, and the main cellular pathways and corresponding transcripts and metabolites were identified. As a result, we found that the energy metabolism between the regions was different. This study provides basic broad data for regenerative medicine in terms of the design of the appropriate microenvironment for in vitro hematopoietic niche modeling, and identifies the normal reference values that can be compared in hematological disease.
Circulating prostate cancer cells have differential resistance to fluid shear stress-induced cell death
Authors: Hope Jacob M. , Bersi Matthew R. , Dombroski Jenna A. , Clinch Andrea B. , Pereles Rebecca S. , Merryman W. David , King Michael R. 
Published: February 2021

ABSTRACT
Circulating tumor cells (CTCs) are exposed to fluid shear stress (FSS) of greater than 1000 dyn/cm2 (100 Pa) in circulation. Normally, CTCs that are exposed to FSS of this magnitude die. However, some CTCs develop resistance to this FSS, allowing them to colonize distant organs. We explored how prostate CTCs can resist cell death in response to forces of this magnitude. The DU145, PC3 and LNCaP human prostate cancer cell lines were used to represent cells of different metastatic origins. The cell lines were briefly treated with an average FSS of 3950 dyn/cm2 (395 Pa) using a 30 G needle and a syringe pump. DU145 cells had no change in cell viability, PC3 cells had some cell death and LNCaP cells exhibited significant cell death. These cell death responses correlated with increased cell membrane damage, less efficient membrane repair and increased stiffness. Additionally, FSS treatment prevented the LNCaP FSS-sensitive cell line from forming a growing tumor in vivo. This suggests that these properties play a role in FSS resistance and could represent potential targets for disrupting blood-borne metastasis.
Nuclear localization of p65 reverses therapy-induced senescence
Authors: Salunkhe Sameer , Mishra Saket V. , Nair Jyothi , Shah Sanket , Gardi Nilesh , Thorat Rahul , Sarkar Debashmita , Rajendra Jacinth , Kaur Ekjot , Dutt Shilpee 
Published: February 2021

ABSTRACT
Senescence is the arrest of cell proliferation and is a tumor suppressor phenomenon. In a previous study, we have shown that therapy-induced senescence of glioblastoma multiforme (GBM) cells can prevent relapse of GBM tumors. Here, we demonstrate that ciprofloxacin-induced senescence in glioma-derived cell lines and primary glioma cultures is defined by SA-β-gal positivity, a senescence-associated secretory phenotype (SASP), a giant cell (GC) phenotype, increased levels of reactive oxygen species (ROS), γ-H2AX and a senescence-associated gene expression signature, and has three stages of senescence –initiation, pseudo-senescence and permanent senescence. Ciprofloxacin withdrawal during initiation and pseudo-senescence reinitiated proliferation in vitro and tumor formation in vivo. Importantly, prolonged treatment with ciprofloxacin induced permanent senescence that failed to reverse following ciprofloxacin withdrawal. RNA-seq revealed downregulation of the p65 (RELA) transcription network, as well as incremental expression of SMAD pathway genes from initiation to permanent senescence. Ciprofloxacin withdrawal during initiation and pseudo-senescence, but not permanent senescence, increased the nuclear localization of p65 and escape from ciprofloxacin-induced senescence. By contrast, permanently senescent cells showed loss of nuclear p65 and increased apoptosis. Pharmacological inhibition or genetic knockdown of p65 upheld senescence in vitro and inhibited tumor formation in vivo. Our study demonstrates that levels of nuclear p65 define the window of reversibility of therapy-induced senescence and that permanent senescence can be induced in GBM cells when the use of senotherapeutics is coupled with p65 inhibitors.
Importin α phosphorylation promotes TPX2 activation by GM130 to control astral microtubules and spindle orientation
Authors: Guo Haijing , Wei Jen-Hsuan , Zhang Yijun , Seemann Joachim 
Published: February 2021

ABSTRACT
Spindle orientation is important in multiple developmental processes as it determines cell fate and function. The orientation of the spindle depends on the assembly of a proper astral microtubule network. Here, we report that the spindle assembly factor TPX2 regulates astral microtubules. TPX2 in the spindle pole area is activated by GM130 (GOLGA2) on Golgi membranes to promote astral microtubule growth. GM130 relieves TPX2 inhibition by competing for importin α1 (KPNA2) binding. Mitotic phosphorylation of importin α at serine 62 (S62) by CDK1 switches its substrate preference from TPX2 to GM130, thereby enabling competition-based activation. Importin α S62A mutation impedes local TPX2 activation and compromises astral microtubule formation, ultimately resulting in misoriented spindles. Blocking the GM130–importin α–TPX2 pathway impairs astral microtubule growth. Our results reveal a novel role for TPX2 in the organization of astral microtubules. Furthermore, we show that the substrate preference of the important mitotic modulator importin α is regulated by CDK1-mediated phosphorylation.
Cutaneous tactile sensitivity before and after tail loss and regeneration in the leopard gecko (Eublepharis macularius)
Authors: Bradley Stefanie S. , Howe Erika , Bent Leah R. , Vickaryous Matthew K. 
Published: February 2021

ABSTRACT
Amongst tetrapods, mechanoreceptors on the feet establish a sense of body placement and help to facilitate posture and biomechanics. Mechanoreceptors are necessary for stabilizing the body while navigating through changing terrains or responding to a sudden change in body mass and orientation. Lizards such as the leopard gecko (Eublepharis macularius) employ autotomy – a voluntary detachment of a portion of the tail – to escape predation. Tail autotomy represents a natural form of significant (and localized) mass loss. Semmes–Weinstein monofilaments were used to investigate the effect of tail autotomy (and subsequent tail regeneration) on tactile sensitivity of each appendage of the leopard gecko. Prior to autotomy, we identified site-specific differences in tactile sensitivity across the ventral surfaces of the hindlimbs, forelimbs and tail. Repeated monofilament testing of both control (tail-intact) and tail-loss geckos had a significant sensitization effect (i.e. decrease in tactile threshold, maintained over time) in all regions of interest except the palmar surfaces of the forelimbs in post-autotomy geckos, compared with baseline testing. Although the regenerated tail is not an exact replica of the original, tactile sensitivity is shown to be effectively restored at this site. Re-establishment of tactile sensitivity on the ventral surface of the regenerate tail points towards a (continued) role in predator detection.
Risk factors for major external structural birth defects among children in Kiambu County, Kenya: a case-control study
Authors: Agot George N. , Mweu Marshal M. , Wang'ombe Joseph K. 
Published: February 2021

Background:Although major external structural birth defects continue to occur globally, the greatest burden is shouldered by resource-constrained countries largely with no surveillance systems. To the best of our knowledge, few studies have been published on the risk factors for these defects in developing countries. The objective of this study was to identify the risk factors for major external structural birth defects among children in Kiambu County, Kenya.Methods:A hospital-based case-control study was used to identify the risk factors for major external structural birth defects in Kiambu County. A structured questionnaire was used to gather information retrospectively on exposure to environmental teratogens, multifactorial inheritance, and sociodemographic-environmental factors during the study participants' last pregnancies. Descriptive analyses (means, standard deviations, medians, and ranges) were used to summarize continuous variables, whereas, categorical variables were summarized as proportions and percentages in frequency tables. Afterward, logistic regression analyses were conducted to estimate the effects of the predictors on major external structural birth defects in the county.Results:From the multivariable analyses, maternal age ≤34 years old, (aOR: 0.41; 95% CI: 0.18-0.91; P=0.03), and preceding siblings with history of birth defects (aOR: 5.21; 95% CI; 1.35-20.12; P =0.02) were identified as the significant predictors of major external structural birth defects.Conclusions:Maternal age ≥35 years old, and siblings with a history of birth defects were identified as the risk factors for major external structural birth defects in Kiambu County, Kenya. This pointed to a need to create awareness among couples against delaying childbearing beyond 35 years of age and the need for clinical genetic services for women of reproductive age with history of births affected by congenital anomalies.
The PINS Trial: a prospective randomized clinical trial comparing a traditional versus an emollient skincare regimen for the care of pin-sites in patients with circular frames
Authors: Ferguson David , Harwood Paul , Allgar Victoria , Roy Anu , Foster Patrick , Taylor Martin , Moulder Elizabeth , Sharma Hemant 
Published: February 2021

Aims Pin-site infection remains a significant problem for patients treated by external fixation. A randomized trial was undertaken to compare the weekly use of alcoholic chlorhexidine (CHX) for pin-site care with an emollient skin preparation in patients with a tibial fracture treated with a circular frame. Methods Patients were randomized to use either 0.5% CHX or Dermol (DML) 500 emollient pin-site care. A skin biopsy was taken from the tibia during surgery to measure the dermal and epidermal thickness and capillary, macrophage, and T-cell counts per high-powered field. The pH and hydration of the skin were measured preoperatively, at follow-up, and if pin-site infection occurred. Pin-site infection was defined using a validated clinical system. Results Out of 116 patients who were enrolled in the study, 23 patients (40%) in the CHX group and 26 (44%) in the DML group had at least one bad or ugly pin-site infection. This difference was not statistically significant (p = 0.71). There was no significant relationship between pH or hydration of the skin and pin-site infection. The epidermal thickness was found to be significantly greater in patients who had a pin-site infection compared with those who did not (p = 0.01). Skin irritation requiring a change of treatment occurred in four patients (7%) using CHX, and none using DML. Conclusion We found no significant difference in the incidence of pin-site infection between the CHX and DML treatment groups. Dermol appeared to offer a small but significant advantage in terms of tolerability. We did not find a significant association between patient or treatment related factors and pin-site infection. It is therefore difficult to make specific recommendations based upon these results. The use of either cleaning agent appears to be appropriate. Cite this article: Bone Joint J 2021;103-B(2):279–285.