bluuebunny/crossref_metadata_2025 huggingface dataset:
Baseline circulating stem-like cells predict survival in patients with metastatic breast Cancer
Authors: Lee Chun-Hui , Hsieh Jason Chia-Hsun , Wu Tyler Min-Hsien , Yeh Ting-Shiuan , Wang Hung-Ming , Lin Yung-Chan , Chen Jen-Shi , Lee Chia-Lin , Huang Wen-Kuan , Hung Tsung-Min , Yen Tzu-Tsen , Chan Sheng-Chieh , Chou Wen-Chi , Kuan Feng-Che , Hu Ching-Chih , Chang Pei-Hung
Published: December 2019

Background

Circulating tumor cells (CTCs) are associated with breast cancer prognosis. Research is limited regarding the role of circulating cancer stem-like cells (cCSCs) considering the treatment response and survival among patients with metastatic breast cancer. Accordingly, we performed this prospective study to clarify the prognostic significance of baseline cCSCs for metastatic breast cancer in terms of first-line chemotherapy.

Methods

Between April 2014 and January 2016, we prospectively enrolled 48 patients with stage IV breast invasive ductal carcinoma who underwent first-line chemotherapy. We identified and analyzed CTCs and cCSCs by using a protocol based on negative selection and flow cytometry before chemotherapy. CTCs were identified as EpCAM+Hoechst+CD45– cells and cCSCs as CD133+EpCAM+Hoechst+CD45– cells. cCSCs were expressed as a percentage of CTCs. The associations between CTCs, cCSCs, and the clinicopathological variables that were predictive of the treatment response and survival outcome were analyzed using univariate and multivariate analyses.

Results

We identified CTCs in all the enrolled patients, with a median number of 33.9/mL CTCs. CSCs were isolated in 97.9% of the patients; the median percentage of cCSCs was 14.7%. A high baseline level of cCSCs was correlated with an inferior tumor response rate (54.2% vs. 95.8%, p < 0.001), overall survival (OS; median: 27.7 months vs. not reached, p < 0.001), and progression-free survival (PFS; median: 5.7 vs. 18.0 months, p < 0.001). Multivariate analysis revealed that along with other clinical variables, baseline cCSCs remained an independent prognostic factor for OS and PFS.

Conclusions

Baseline cCSCs predict the treatment response as well as survival in patients with metastatic breast cancer undergoing first-line chemotherapy. Therefore, the measurement of cCSCs may assist in identifying early cancer treatment response and prognosis.
Correlation of prechemotherapy urinary megalin ectodomain (A-megalin) levels with the development of cisplatin-induced nephrotoxicity: a prospective observational study
Authors: Shoji Satoshi , Hosojima Michihiro , Kabasawa Hideyuki , Kondo Rie , Miura Satoru , Watanabe Satoshi , Aoki Nobumasa , Kaseda Ryohei , Kuwahara Shoji , Tanabe Naohito , Hirayama Yoshiaki , Narita Ichiei , Kikuchi Toshiaki , Kagamu Hiroshi , Saito Akihiko
Published: December 2019

Background

Cisplatin is a potent chemotherapeutic agent used to treat a variety of solid tumors. One of the major side effects of cisplatin is dose-limiting nephrotoxicity. We recently demonstrated that the renal uptake of cisplatin and resultant cisplatin-induced nephrotoxicity are mediated in part by megalin, an endocytic receptor in proximal tubule epithelial cells (PTECs). We also developed sandwich enzyme-linked immunosorbent assays to measure the megalin ectodomain (A-megalin) and full-length megalin (C-megalin) in urine using monoclonal antibodies against the amino- and carboxyl-termini of megalin, respectively. The present study examined the correlation of urinary megalin level with cisplatin-induced nephrotoxicity and its utility as a biomarker in patients with thoracic cancer.

Methods

This prospective observational study involved 45 chemotherapy-naïve patients scheduled to receive chemotherapy with ≥60 mg/m2 cisplatin for histologically diagnosed small cell lung cancer, non-small cell lung cancer, or malignant pleural mesothelioma. Before and after the first course of chemotherapy, we measured urinary A- and C-megalin and other markers of PTEC injury, such as N-acetyl-β-D-glucosaminidase, α1-microglobulin, β2-microglobulin, neutrophil gelatinase-associated lipocalin, and liver-type fatty acid-binding protein, and compared the values with the change in the estimated glomerular filtration rate (eGFR) and clinical risk factors for renal impairment.

Results

A negative correlation was found between baseline urinary A-megalin levels and change in eGFR (r = − 0.458, P = 0.002). According to Kaplan–Meier survival curves, eGFR decline was associated with the baseline urinary A-megalin quartile (P = 0.038). In addition, according to the hazard ratios (HRs) for eGFR decline > 10 mL/min/1.73 m2 calculated using a Cox proportional hazard model, the highest quartile had a significantly higher risk of eGFR decline compared with the lowest quartile (HR 7.243; 95% confidence interval 1.545–33.962). Other baseline urinary markers showed no correlation with eGFR decline.

Conclusions

This is the first report demonstrating that prechemotherapy urinary A-megalin levels are correlated with the development of cisplatin-induced nephrotoxicity. This finding has clinical implications for the identification of patients at risk for cisplatin-induced nephrotoxicity and the development of possible prophylactic therapies.
Effectiveness of inpatient versus outpatient complex treatment programs in depressive disorders: a quasi-experimental study under naturalistic conditions
Authors: Driessen Martin , Schulz Philipp , Jander Silvia , Ribbert Hedda , Gerhards Stefanie , Neuner Frank , Koch-Stoecker Steffi
Published: December 2019

Background

Due to long waiting periods for outpatient psychotherapy and the high resource requirements of inpatient treatment, there is a need for alternative treatment programs for patients with depressive disorders. Thus, we investigated the effectiveness of the “Bielefeld OutpatientIntensive Treatment Program ofDepression” (BID) in comparison with a typical inpatient treatment program by using a prospective quasi-experimental observational study. We assumed (i) that both complex programs are effective in pre-post analyses after 6 weeks and (ii) that inpatient treatment is more effective compared with the outpatient program.

Methods

Four hundred patients with depressive psychopathology – a majority with depressive episodes (ICD-10 F3X) - took part in the BID and 193 in the inpatient program. Different self- (i.e., BDI) and expert measures (i.e., MADRS) of psychopathology at baseline (t1) and 6 weeks later (t2) were applied to examine treatment effects.

Results

Treatment effects were high in separate analyses of both groups with Cohen’sdranging from 1.10 to 1.76., while ANOVA comparative analyses did not reveal any significant differences between both treatment settings nor did a set of independent covariates analyzed here. Response rates of BDI (p = .002) and MADRS (p = .001) were higher in the outpatient group. Results indicate BID not to be inferior compared to an inpatient program, although diverging pathways to treatment, higher rates of clinical recurrent depressive disorders and severe episodes as well as lower rates of employment and partnership in the inpatient treatment group have to be considered.

Conclusion

Outpatient intensive treatment programs may represent a solution for patients needing more than a treatment session once per week but less than a complex inpatient or day clinic program.
The effectiveness of using a WeChat account to improve exclusive breastfeeding in Huzhu County Qinghai Province, China: protocol for a randomized control trial
Authors: Wu Qiong , Huang Yiwen , van Velthoven Michelle Helena , Wang Wei , Chang Suying , Zhang Yanfeng
Published: December 2019

Background

An exclusive breastfeeding rate in the first 6 months of life of at least 50% is one of the six World Health Organization global nutrition targets for 2025. However, the exclusive breastfeeding rate in China is quite low and decreasing which makes it urgent to explore effective ways to reverse the current downward trend. As mobile technologies have rapidly developed, mobile communication apps such as WeChat (one of the largest social networking platforms in China) are well accepted and have the potential to improve health behaviors in a convenient way. The current paper describes the study protocol of a WeChat intervention that aims to promote breastfeeding in rural areas in China.

Methods

The study is designed as a randomized controlled trial in rural Qinghai Province, China. Women who are 14–36 weeks pregnant will be randomized to routine antenatal and postnatal care, or routine care plus the WeChat breastfeeding education. pregnant women with a severe disease and complications of pregnancy or HIV-1 will be excluded. Breastfeeding knowledge and promotion information will be delivered to the intervention group through a WeChat official account from 3 months pregnancy to 6 months postpartum. The outcome assessments are conducted at baseline through face-to-face interviews, and at one week, 1 month, 3 months and 6 months postpartum by telephone interviews. The primary outcome is difference in the exclusive breastfeeding rate at 1 month, 3 months, and 6 months postpartum between the intervention group and the control group. Secondary outcomes include the overall duration of any and exclusive breastfeeding across the first 6 months postpartum; mothers’ knowledge of breastfeeding; the proportion of early initiation of breastfeeding; and the timing of the introduction of solid food to infants. Intention-to-treat-analysis will be used. Survival analysis will be used to compare the overall duration of any and exclusive breastfeeding between groups.

Discussion

This study is the first effort to promote exclusive breastfeeding through WeChat in China. Our results will provide scientific evidence for the effect of health education through WeChat on breastfeeding. Thereby this may offer a comprehensive intervention to promote exclusive breastfeeding in China and other settings.

Trial registration

Chinese Clinical Trial Registry –ChiCTR1800017364. Registered 26 July 2018. http://www.chictr.org.cn/showproj.aspx?proj=29325
Protecting our future generation: study protocol for a randomized controlled trial evaluating a sexual health self-care intervention with Native American youth and young adults
Authors: Lauren Tingey , Catherine Sutcliffe , Rachel Chambers , Hima Patel , Angelita Lee , Shauntel Lee , Laura Melgar , Anna Slimp , Anne Rompalo , Mariddie Craig , Charlotte Gaydos
Published: December 2019

Background

Disparities in sexually transmitted infections (STI) are an urgent problem among Native American youth and young adults which are not fully explained by different sexual or related behaviors. These sexual health disparities are more likely attributed to social environments and structural determinants such as a shortage of sexual healthcare providers, lower socioeconomic status, and access barriers to STI screening and treatment, including geographic isolation and confidentiality concerns. Innovative, non-clinic based alternatives to promote STI screening and treatment are essential for alleviating these disparities. Self-care, or the care taken by individuals towards their own health and well-being may be such a strategy. This study will assess the efficacy of a self-care intervention, called Protecting Our Future Generation, for increasing uptake of STI screening and impacting sexual risk and protective behaviors among Native American youth and young adults living in a reservation-based community in the Southwestern United States.

Methods

The proposed study is a randomized controlled trial to test the efficacy of a self-care intervention compared to a control condition. Participants will be Native Americans ages 14–26 years old who have had vaginal or anal sex at least once in their lifetime. Participants will be randomized to the intervention which includes: 1) a sexual health self-assessment with embedded clinical prediction tool predicting STI positivity, and 2) personalized messaging with key steps to lower risk for STIs, or the control condition which includes: 1) a self-assessment about water, soda and sugar sweetened beverage consumption, and 2) personalized messaging to meet recommended daily intake. All participants will be offered a self-administered STI test. Participants will complete assessments at baseline, 3- and 6-months follow-up. The primary outcome measure is completion of STI screening.

Discussion

Protecting Our Future Generation is among the first self-care interventions uniquely focused on sexual health among a Native American population, who endure significant sexual health disparities and are under-represented in research. If efficacious, the intervention will be a model of sexual health self-care for Native American youth and young adults adaptable for use in healthcare and community-based settings.

Trial registration

Clinical Trials: http://clinicaltrials.gov; NCT03895320; Registered 03/28/2019.
Association between Helicobacter pylori infection and dental pulp reservoirs in Japanese adults
Authors: Iwai Komei , Watanabe Isao , Yamamoto Toshiro , Kuriyama Nagato , Matsui Daisuke , Nomura Ryota , Ogaya Yuko , Oseko Fumishige , Adachi Keiji , Takizawa Shigeta , Ozaki Etsuko , Koyama Teruhide , Nakano Kazuhiko , Kanamura Narisato , Uehara Ritei , Watanabe Yoshiyuki
Published: December 2019

Background

Helicobacter pylori(H. pylori) colonize the stomach and are considered an etiological agent of gastric cancer. The oral cavity is a transmission route to the stomach, but the exact site of colonization has not yet been explicated. Our study investigated the association betweenH. pyloriinfection and presence in oral samples.

Methods

Dental pulp, supragingival plaque, and saliva from 192 patients visiting the Dentistry’s outpatient clinic were collected for testing. TheH. pylori ureAgene was identified via Nested PCR. Urine anti-H. pyloriantibody test was utilized to detect infection.

Results

Twenty-five subjects were found to be antibody-positive. PCR analysis of dental pulp revealed that 23 subjects possessed theureAgene. Twenty-one subjects were positive for both antibodies and genes in dental pulp. PCR testing revealed that 2 subjects were positive in dental plaque but negative for saliva. The subjects positive forH. pyloriin dental pulp expressed clinical signs of severe dental caries.

Conclusions

H. pyloriinfected subjects expressedH. pyloriin samples from the oral cavity. The main reservoir for infection within the oral cavity was determined to be dental pulp. Moreover,H. pyloriare likely transmitted from dental caries to the root canal.
Use of a voluntary testing program to study the spatial epidemiology of Johne’s disease affecting dairy herds in Minnesota: a cross sectional study
Authors: Kanankege K. S. T. , Machado G. , Zhang L. , Dokkebakken B. , Schumann V. , Wells S. J. , Perez A. M. , Alvarez J.
Published: December 2019

Background

One of the key steps in the management of chronic diseases in animals including Johne’s disease (JD), caused byMycobacterium avium subsp. paratuberculosis(MAP), is the ability to track disease incidence over space and time. JD surveillance in the U.S. dairy cattle is challenging due to lack of regulatory requirements, imperfect diagnostic tests, and associated expenses, including time and labor. An alternative approach is to use voluntary testing programs. Here, data from a voluntary JD testing program, conducted by the Minnesota Dairy Herd Improvement Association, were used to: a) explore whether such a program provides representative information on JD-prevalence in Minnesota dairy herds, b) estimate JD distribution, and, c) identify herd and environmental factors associated with finding JD-positive cows. Milk samples (n = 70,809) collected from 54,652 unique cows from 600 Minnesota dairy herds between November 2014 and April 2017 were tested using a MAP antibody ELISA. Participant representativeness was assessed by comparing the number of JD-tested herds with the number of herds required to estimate the true disease prevalence per county based on official statistics from the National Agricultural Statistical Services. Multivariable logistic regression models, with and without spatial dependence between observations, were then used to investigate the association between herd status to JD (positive/negative), as indicated by milk ELISA results, and available covariates at the herd level.

Results

Within the study population, at least one test-positive cow was found in 414 of 600 (69%) herds. Results indicated that large herds that test frequently and herds located in loamy or silt soils are more likely to have at least one MAP test-positive cow. After adjusting for herd size, testing frequency, and soil type, there was no spatial dependence in JD risk between neighboring dairies within 5 to 20 km. Furthermore, the importance of collecting data on herd management, feed, and biosecurity for insightful interpretations was recognized. The study suggested that, although limited, the voluntary testing database may support monitoring JD status.

Conclusions

Results presented here help elucidate the spatial characteristics of JD in Minnesota and the study may ultimately contribute to the design and implementation of surveillance programs for the disease.
A review of the WHO malaria rapid diagnostic test product testing programme (2008–2018): performance, procurement and policy
Authors: Cunningham Jane , Jones Sophie , Gatton Michelle L. , Barnwell John W. , Cheng Qin , Chiodini Peter L. , Glenn Jeffrey , Incardona Sandra , Kosack Cara , Luchavez Jennifer , Menard Didier , Nhem Sina , Oyibo Wellington , Rees-Channer Roxanne R. , Gonzalez Iveth , Bell David
Published: December 2019

Malaria rapid diagnostic tests (RDTs) emerged in the early 1990s into largely unregulated markets, and uncertain field performance was a major concern for the acceptance of tests for malaria case management. This, combined with the need to guide procurement decisions of UN agencies and WHO Member States, led to the creation of an independent, internationally coordinated RDT evaluation programme aiming to provide comparative performance data of commercially available RDTs. Products were assessed against Plasmodium falciparum and Plasmodium vivax samples diluted to two densities, along with malaria-negative samples from healthy individuals, and from people with immunological abnormalities or non-malarial infections. Three measures were established as indicators of performance, (i) panel detection score (PDS) determined against low density panels prepared from P. falciparum and P. vivax wild-type samples, (ii) false positive rate, and (iii) invalid rate, and minimum criteria defined. Over eight rounds of the programme, 332 products were tested. Between Rounds 1 and 8, substantial improvements were seen in all performance measures. The number of products meeting all criteria increased from 26.8% (11/41) in Round 1, to 79.4% (27/34) in Round 8. While products submitted to further evaluation rounds under compulsory re-testing did not show improvement, those voluntarily resubmitted showed significant increases in P. falciparum (p = 0.002) and P. vivax PDS (p < 0.001), with more products meeting the criteria upon re-testing. Through this programme, the differentiation of products based on comparative performance, combined with policy changes has been influential in the acceptance of malaria RDTs as a case-management tool, enabling a policy of parasite-based diagnosis prior to treatment. Publication of product testing results has produced a transparent market allowing users and procurers to clearly identify appropriate products for their situation, and could form a model for introduction of other, broad-scale diagnostics.
Association between micronutrient deficiency and acute respiratory infections in healthy adults: a systematic review of observational studies
Authors: Wang Min Xian , Koh Jiayun , Pang Junxiong
Published: December 2019

Background

Acute respiratory infections (ARI), including the common cold causes significant morbidity and economical losses globally. Micronutrient deficiency may increase ARI incidence risk and its associated duration and severity among healthy adults, but evidence are inconclusive. This study aims to systematically review all observations on the association between single micronutrient deficiency and ARI incidence, duration and severity in healthy adults.

Methods

Systematic literature searches were conducted in PubMed, Cochrane Library, Embase and Scopus databases. Eligible studies were assessed for the reporting and methodological quality. Adjusted summary statistics with their relevant 95% confidence intervals or interquartile ranges were extracted for the outcomes of interest.

Results

The literature search identified 423 unique studies. Of which, only eight studies were eligible and included in the final review. Only vitamin D deficiency (VDD) was observed among these eight studies. There were no eligible studies that focused on the association between other single micronutrient deficiency and ARI. The review found mixed observations on ARI incidence, and a lack of evidence on its associated severity to conclude the association between VDD and these outcomes. However, existing evidence consistently suggested that VDD is likely to lead to longer ARI duration (median duration in days: deficient group, 4 to 13; non-deficient groups, 2 to 8).

Conclusion

This review found that VDD may be associated to longer ARI duration, but its effect on ARI incidence and its associated severity among healthy adults remains inconclusive. This review also highlighted the lack of a consistent regional and/or global definition for micronutrient sufficiency, and that future studies should explore and conclude the association between other micronutrient deficiency and ARIs in healthy adults before considering supplementation for ARI prevention and management.
LncRNA LINRIS stabilizes IGF2BP2 and promotes the aerobic glycolysis in colorectal cancer
Authors: Wang Yun , Lu Jia-Huan , Wu Qi-Nian , Jin Ying , Wang De-Shen , Chen Yan-Xing , Liu Jia , Luo Xiao-Jing , Meng Qi , Pu Heng-Ying , Wang Ying-Nan , Hu Pei-Shan , Liu Ze-Xian , Zeng Zhao-Lei , Zhao Qi , Deng Rong , Zhu Xiao-Feng , Ju Huai-Qiang , Xu Rui-Hua
Published: December 2019

Background

Long noncoding RNAs (lncRNAs) play nonnegligible roles in the epigenetic regulation of cancer cells. This study aimed to identify a specific lncRNA that promotes the colorectal cancer (CRC) progression and could be a potential therapeutic target.

Methods

We screened highly expressed lncRNAs in human CRC samples compared with their matched adjacent normal tissues. The proteins that interact with LINRIS (Long Intergenic Noncoding RNA for IGF2BP2 Stability) were confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. The proliferation and metabolic alteration of CRC cells with LINRIS inhibited were tested in vitro and in vivo.

Results

LINRIS was upregulated in CRC tissues from patients with poor overall survival (OS), and LINRIS inhibition led to the impaired CRC cell line growth. Moreover, knockdown of LINRIS resulted in a decreased level of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), a newly found N6-methyladenosine (m6A) ‘reader’. LINRIS blocked K139 ubiquitination of IGF2BP2, maintaining its stability. This process prevented the degradation of IGF2BP2 through the autophagy-lysosome pathway (ALP). Therefore, knockdown of LINRIS attenuated the downstream effects of IGF2BP2, especially MYC-mediated glycolysis in CRC cells. In addition, the transcription of LINRIS could be inhibited by GATA3 in CRC cells. In vivo experiments showed that the inhibition of LINRIS suppressed the proliferation of tumors in orthotopic models and in patient-derived xenograft (PDX) models.

Conclusion

LINRIS is an independent prognostic biomarker for CRC. The LINRIS-IGF2BP2-MYC axis promotes the progression of CRC and is a promising therapeutic target.
Amplified intracellular Ca2+ for synergistic anti-tumor therapy of microwave ablation and chemotherapy
Authors: Dou Jian-ping , Wu Qiong , Fu Chang-hui , Zhang Dong-yun , Yu Jie , Meng Xian-wei , Liang Ping
Published: December 2019

Background

Developing new strategies to reduce the output power of microwave (MW) ablation while keeping anti-tumor effect are highly desirable for the simultaneous achievement of effective tumor killing and avoidance of complications. We find that mild MW irradiation can significantly increase intracellular Ca2+ concentration in the presence of doxorubicin hydrochloride (DOX) and thus induce massive tumor cell apoptosis. Herein, we designed a synergistic nanoplatform that not only amplifies the intracellular Ca2+ concentration and induce cell death under mild MW irradiation but also avoids the side effect of thermal ablation and chemotherapy.

Results

The as-made NaCl–DOX@PLGA nanoplatform selectively elevates the temperature of tumor tissue distributed with nanoparticles under low-output MW, which further prompts the release of DOX from the PLGA nanoparticles and tumor cellular uptake of DOX. More importantly, its synergistic effect not only combines thermal ablation and chemotherapy, but also obviously increases the intracellular Ca2+ concentration. Changes of Ca2+ broke the homeostasis of tumor cells, decreased the mitochondrial inner membrane potential and finally induced the cascade of apoptosis under nonlethal temperature. As such, the NaCl–DOX@PLGA efficiently suppressed the tumor cell progression in vivo and in vitro under mild MW irradiation for the triple synergic effect.

Conclusions

This work provides a biocompatible and biodegradable nanoplatform with triple functions to realize the effective tumor killing in unlethal temperature. Those findings provide reliable solution to solve the bottleneck problem bothering clinics about the balance of thermal efficiency and normal tissue protection.
Molecular analysis of the effects of steroid hormones on mouse meiotic prophase I progression
Authors: Burks Deion M. , McCoy Margaret R. , Dutta Sudipta , Mark-Kappeler Connie J. , Hoyer Patricia B. , Pepling Melissa E.
Published: December 2019

Background

Infertility is linked to depletion of the primordial follicle pool consisting of individual oocytes arrested at the diplotene stage of meiotic prophase I surrounded by granulosa cells. Primordial germ cells, the oocyte precursors, begin to differentiate during embryonic development. These cells migrate to the genital ridge and begin mitotic divisions, remaining connected, through incomplete cytokinesis, in clusters of synchronously dividing oogonia known as germ cell cysts. Subsequently, they enter meiosis, become oocytes and progress through prophase I to the diplotene stage. The cysts break apart, allowing individual oocytes to be surrounded by a layer of granulosa cells, forming primordial follicles each containing a diplotene arrested oocyte. A large number of oocytes are lost coincident with cyst breakdown, and may be important for quality control of primordial follicle formation. Exposure of developing ovaries to exogenous hormones can disrupt cyst breakdown and follicle formation, but it is unclear if hormones affect progression of oocytes through prophase I of meiosis.

Methods

Fetal ovaries were treated in organ culture with estradiol, progesterone, or both hormones, labeled for MSY2 or Synaptonemal complex protein 3 (SYCP3) using whole mount immunocytochemistry and examined by confocal microscopy. Meiotic prophase I progression was also followed using the meiotic surface spread technique.

Results

MSY2 expression in oocytes was reduced by progesterone but not estradiol or the hormone combination. However, while MSY2 expression was upregulated during development it was not a precise marker for the diplotene stage. We also followed meiotic prophase I progression using antibodies against SYCP3 using two different methods, and found that the percent of oocytes at the pachytene stage peaked at postnatal day 1. Finally, estradiol and progesterone treatment together but not either alone in organ culture increased the percent of oocytes at the pachytene stage.

Conclusions

We set out to examine the effects of hormones on prophase I progression and found that while MSY2 expression was reduced by progesterone, MSY2 was not a precise diplotene stage marker. Using antibodies against SYCP3 to identify pachytene stage oocytes we found that progesterone and estradiol together delayed progression of oocytes through prophase I.
Microglial activation by microbial neuraminidase through TLR2 and TLR4 receptors
Authors: Fernández-Arjona María del Mar , Grondona Jesús M. , Fernández-Llebrez Pedro , López-Ávalos María Dolores
Published: December 2019

Background

Neuraminidase (NA) is a sialidase present, among various locations, in the envelope/membrane of some bacteria/viruses (e.g., influenza virus), and is involved in infectiveness and/or dispersion. The administration of NA within the brain lateral ventricle represents a model of acute sterile inflammation. The relevance of the Toll-like receptors TLR2 and TLR4 (particularly those in microglial cells) in such process was investigated.

Methods

Mouse strains deficient in either TLR2 (TLR2-/-) or TLR4 (TLR4-/-) were used. NA was injected in the lateral ventricle, and the inflammatory reaction was studied by immunohistochemistry (IBA1 and IL-1β) and qPCR (cytokine response). Also, microglia was isolated from those strains and in vitro stimulated with NA, or with TLR2/TLR4 agonists as positive controls (P3C and LPS respectively). The relevance of the sialidase activity of NA was investigated by stimulating microglia with heat-inactivated NA, or with native NA in the presence of sialidase inhibitors (oseltamivir phosphate and N-acetyl-2,3-dehydro-2-deoxyneuraminic acid).

Results

In septofimbria and hypothalamus, IBA1-positive and IL-1β-positive cell counts increased after NA injection in wild type (WT) mice. In TLR4-/-mice, such increases were largely abolished, while were only slightly diminished in TLR2-/-mice. Similarly, the NA-induced expression of IL-1β, TNFα, and IL-6 was completely blocked in TLR4-/-mice, and only partially reduced in TLR2-/-mice. In isolated cultured microglia, NA induced a cytokine response (IL-1β, TNFα, and IL-6) in WT microglia, but was unable to do so in TLR4-/-microglia; TLR2 deficiency partially affected the NA-induced microglial response. When WT microglia was exposed in vitro to heat-inactivated NA or to native NA along with sialidase inhibitors, the NA-induced microglia activation was almost completely abrogated.

Conclusions

NA is able to directly activate microglial cells, and it does so mostly acting through the TLR4 receptor, while TLR2 has a secondary role. Accordingly, the inflammatory reaction induced by NA in vivo is partially dependent on TLR2, while TLR4 plays a crucial role. Also, the sialidase activity of NA is critical for microglial activation. These results highlight the relevance of microbial NA in the neuroinflammation provoked by NA-bearing pathogens and the possibility of targeting its sialidase activity to ameliorate its impact.
The evolution of a bat population with white-nose syndrome (WNS) reveals a shift from an epizootic to an enzootic phase
Authors: Frank Craig L. , Davis April D. , Herzog Carl
Published: December 2019

Background

White-nose Syndrome (WNS) is a mycosis caused by a cutaneous infection with the fungus Pseudogymnoascus destructans (Pd). It produces hibernation mortality rates of 75–98% in 4 bats: Myotis lucifugus, M. septentrionalis, M. sodalis, and Perimyotis subflavus. These high mortality rates were observed during the first several years after the arrival of P. destructans at a hibernation site. Mortality is caused by a 60% decrease in torpor bout duration, which results in a premature depletion of depot fat prior to spring.

Results

Little is known about the long-term effects of Pd on torpor and mortality, thus we conducted a 9-year study on M. lucifugus at 5 of the hibernation sites where Pd first appeared in North America during the winter of 2007–08. The M. lucifugus hibernating at one of these sites one year after the arrival of Pd (2008–09) had: a) a mean torpor bout duration of 7.6 d, b) no depot fat reserves by March, and c) an apparent over-winter mortality rate of 88%. The M. lucifugus hibernating at this same site 6–9 years after the arrival of Pd, in contrast, had: a) a mean torpor bout duration of 14.7 d, b) depot fat remaining in March, and c) an apparent mortality rate of 50%. The number of M. lucifugus hibernating at 2 of these sites has consistently increased since 2010 and is now more than 3.0-fold higher than the number remaining after the winter of 2008–09.

Conclusions

These findings indicate that this population of M. lucifugus has evolved mechanisms to hibernate well in the presence of Pd, thus reducing over-winter mortality.
Assesment and interpretation of negative forelimb allometry in the evolution of non-avian Theropoda
Authors: Palma Liberona José A. , Soto-Acuña Sergio , Mendez Marco A. , Vargas Alexander O.
Published: December 2019

Background

The origin of birds is marked by a significant decrease in body size along with an increase in relative forelimb size. However, before the evolution of flight, both traits may have already been related: It has been proposed that an evolutionary trend of negative forelimb allometry existed in non-avian Theropoda, such that larger species often have relatively shorter forelimbs. Nevertheless, several exceptions exist, calling for rigorous phylogenetic statistical testing.

Results

Here, we re-assessed allometric patterns in the evolution of non-avian theropods, for the first time taking into account the non-independence among related species due to shared evolutionary history.

We confirmed a main evolutionary trend of negative forelimb allometry for non-avian Theropoda, but also found support that some specific subclades (Coelophysoidea, Ornithomimosauria, and Oviraptorosauria) exhibit allometric trends that are closer to isometry, losing the ancestral negative forelimb allometry present in Theropoda as a whole.

Conclusions

Explanations for negative forelimb allometry in the evolution of non-avian theropods have not been discussed, yet evolutionary allometric trends often reflect ontogenetic allometries, which suggests negative allometry of the forelimb in the ontogeny of most non-avian theropods. In modern birds, allometric growth of the limbs is related to locomotor and behavioral changes along ontogeny. After reviewing the evidence for such changes during the ontogeny of non-avian dinosaurs, we propose that proportionally longer arms of juveniles became adult traits in the small-sized and paedomorphic Aves.
A quick and efficient hydroponic potato infection method for evaluating potato resistance and Ralstonia solanacearum virulence
Authors: Wang Huijuan , Hu Jinxue , Lu Yao , Zhang Mancang , Qin Ning , Zhang Ruize , He Yizhe , Wang Dongdong , Chen Yue , Zhao Cuizhu , Coll Núria S. , Valls Marc , Chen Qin , Lu Haibin
Published: December 2019

Background

Potato, the third most important crop worldwide, plays a critical role in human food security. Brown rot, one of the most destructive potato diseases caused by Ralstonia solanacearum, results in huge economic losses every year. A quick, stable, low cost and high throughout method is required to meet the demands of identification of germplasm resistance to bacterial wilt in potato breeding programs.

Results

Here we present a novel R. solanacearum hydroponic infection assay on potato plants grown in vitro. Through testing wilt symptom appearance and bacterial colonization in aerial part of plants, we found that the optimum conditions for in vitro potato infection were using an OD600 0.01 bacterial solution suspended with tap water for infection, broken potato roots and an open container. Infection using R. solanacearum strains with differential degree of aggressivity demonstrated that this infection system is equally efficient as soil-drench inoculation for assessment of R. solanacearum virulence on potato. A small-scale assessment of 32 potato germplasms identified three varieties highly resistant to the pathogen, which indicates this infection system is a useful method for high-throughout screening of potato germplasm for resistance. Furthermore, we demonstrate the utility of a strain carrying luminescence to easily quantify bacterial colonization and the detection of latent infections in hydroponic conditions, which can be efficiently used in potato breeding programs.

Conclusions

We have established a quick and efficient in vitro potato infection system, which may facilitate breeding for new potato cultivars with high resistance to R. solanacearum.
Is deliberate hypotension a safe technique for orthopedic surgery?: a systematic review and meta-analysis of parallel randomized controlled trials
Authors: Jiang Jia , Zhou Ran , Li Bo , Xue Fushan
Published: December 2019

Background

Deliberate hypotension has been shown to reduce the intraoperative bleeding and the need for allogeneic blood transfusion, and improve the surgical field, but there is still controversy on its clinical safety. This systematic review was designed to assess the safety and benefits of deliberate hypotension for orthopedic surgery.

Methods

The review met the requirements of the PRISMA guidelines. The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, ISI Web of Science, ScienceDirect, and four Chinese databases (China National Knowledge Infrastructure, Wanfang, vip citation database, and updated version of China Biology Medicine disc from January 1, 2000 to January 1, 2019) were searched. All parallel randomized controlled trials comparing the effects of using deliberate hypotension with not using deliberate hypotension on clinical outcomes of patients undergoing orthopedic surgery were selected. The primary outcome was overall mortality. The secondary outcomes were the intraoperative blood loss, blood transfusion volume, and serious adverse postoperative events.

Results

A total of 30 studies with 36 comparisons (1454 participants) were included in meta-analysis. Two studies with 120 participants reported overall mortality and the result was zero (low-quality evidence). The use of deliberate hypotension reduced the intraoperative blood loss (mean difference, − 376.7; 95% CI − 428.1 to − 325.3; I2 = 94%; 29 studies, 36 comparisons, and 1398 participants; low-quality evidence) and blood transfusion volume (mean difference, − 242.5; 95% CI − 302.5 to − 182.6; I2 = 95%; 13 studies, 14 comparisons, and 544 participants; low-quality evidence). Six studies with 286 participants reported the occurrence of serious adverse postoperative events and the result was zero (low-quality evidence). Subgroup analyses according to age groups, controlled mean artery pressure levels, types of orthopedic surgeries, different combinations of other blood conservative method, and hypotensive methods mostly did not explain heterogeneity; significant differences were identified in almost all subgroups.

Conclusions

Based on the available evidence, it is still unclear whether or not deliberate hypotension is a safe technique for orthopedic surgery due to limited studies with very small sample size, though it may decrease the intraoperative blood loss and blood transfusion volume irrespective of age groups, controlled mean artery pressure levels, types of surgeries, hypotensive methods, or different combinations of other blood conservation strategies.

Trial registration

PROSPERO CRD42016045480.
Murine patellar tendon transplantation requires transosseous cerclage augmentation — development of a transplantation model for investigation of systemic and local drivers of healing
Authors: Frankewycz Borys , Cimino Daniel , Andarawis-Puri Nelly
Published: December 2019

Background

Tendon injuries are common musculoskeletal injuries that heal with scar tissue formation, often achieving reduced biomechanical and functional properties. The murine patellar tendon is a research tool that holds potential for investigating tendon healing and can be useful for exploring therapeutic strategies. Since healing is a complex process that results from the collaboration between the systemic and local tissue environment, a murine tendon transplantation model that can be applied to transgenic mice and genetic mutants would allow isolation of systemic versus local tendon factors in driving effective tendon healing. Preliminary studies have shown that transplantation with simple tendon sutures results in a proximalization of the patellar bone due to the involuntary quadriceps muscle force leading to tearing of the graft and failure of the knee extensor mechanism. To avoid this elongation of the graft, two cerclage techniques for murine patellar tendon transplantation were introduced and validated.

Methods

Three developed surgical techniques (no-cerclage-augmentation (NCA)), transfascial suture cerclage with encirclement of the patellar tendon (TFSC), and dual-cerclage-augmentation with a transosseous bone-to-bone cerclage through the patella bone and an additional musculotendinous cerclage (DCA)) were compared at 4 and 8 weeks macroscopically in regards to graft continuity, cerclage integrity, gap formation, and radiologically by measuring the patello-tibial distance and using a patella bone position grading system.

Results

The NCA group showed complete failure at 5–7 days after surgery. The TFSC has led to 69% functional failure of the cerclage. In contrast, the DCA with a has led to 78% success with improvement in patellar bone position and a similar patello-tibial distance to the naïve contralateral murine knees over the time period of 8 weeks.

Conclusions

This study shows that a bone-to-bone cerclage is necessary to maintain a desired graft length in murine patellar tendon models. This surgery technique can serve for future graft trans- and implantations in the murine patellar tendon.
Schaaf-Yang syndrome shows a Prader-Willi syndrome-like phenotype during infancy
Authors: Negishi Yutaka , Ieda Daisuke , Hori Ikumi , Nozaki Yasuyuki , Yamagata Takanori , Komaki Hirofumi , Tohyama Jun , Nagasaki Keisuke , Tada Hiroko , Saitoh Shinji
Published: December 2019

Background

Schaaf-Yang syndrome (SYS) is a newly recognized imprinting related syndrome, which is caused by a truncating variant in maternally imprintedMAGEL2located in 15q11-q13.Yet, precise pathomechanism remains to be solved. We sequencedMAGEL2in patients suspected Prader-Willi syndrome (PWS) to delineate clinical presentation of SYS. We examined 105 patients with clinically suspected PWS but without a specific PWS genetic alteration. Sanger sequencing of the entireMAGEL2gene and methylation-specific restriction enzyme treatment to detect the parent of origin were performed. Clinical presentation was retrospectively assessed in detail.

Results

Truncating variants inMAGEL2were detected in six patients (5.7%), including a pair of siblings. All truncating variants in affected patients were on the paternally derived chromosome, while the healthy father of the affected siblings inherited the variant from his mother. Patients withMAGEL2variants shared several features with PWS, such as neonatal hypotonia, poor suck, and obesity; however, there were also unique features, including arthrogryposis and a failure to acquire meaningful words. Additionally, an episode of neurological deterioration following febrile illness was confirmed in four of the six patients, which caused severe neurological sequalae.

Conclusions

SYS can be present in infants suspected with PWS but some unique features, such as arthrogryposis, can help discriminate between the two syndromes. An episode of neurological deterioration following febrile illness should be recognized as an important complication.
Intramedullary reaming modality for management of postoperative long bone infection: a prospective randomized controlled trial in 44 patients
Authors: Finelli Carlos Augusto , dos Reis Fernando Baldy , Fernandes Helio Alvachian , Dell’Aquila Adriana , Carvalho Rogério , Miki Natalia , Franciozi Carlos , Abdalla Rene , Salles Mauro José Costa
Published: December 2019

Background

Studies addressing the management of intramedullary infection are mainly retrospective and with a limited number of cases. Reaming can be performed using either conventional reaming or using the reamer/irrigator/aspirator (RIA) system. Until now there have been no comparative prospective studies between these two methods. We aimed to compare the efficacy of RIA with conventional reaming followed by insertion of antibiotic-loaded cement, for the treatment of intramedullary nail infection of long bones. We assessed the rate of remission between groups after two-year follow-up and identified microorganisms using tissue cultures and sonication of explanted intramedullary nail (IMN).

Methods

A noninferiority, randomized clinical trial was carried out between August 2013 and August 2015 involving 44 patients of whom a locked IMN implant of the femur and/or tibia was retrieved and who all met the clinical and radiological criteria for IMN-associated osteomyelitis. Patients were randomized into two groups: RIA alone versus conventional reaming followed by antibiotic-loaded cement insertion. Both groups also underwent six-weeks of antibiotic treatment according to the results of the antibiogram. Patients were evaluated after 1, 3, 6, 12 and 24 months for radiological and clinical follow-up.

Results

After 24 months, the rate of infection remission was similar between the two groups, 87% in the RIA group and 95.5% in the conventional reaming group (p = 0.60). Among four patients who had recurrence of infection, the time to reappearance of symptoms varied from 20 days to twenty-two months. Staphylococcus aureus and coagulase-negative Staphylococci were isolated in 23 (40.4%) and 13 (22.9%) patients, respectively. Interestingly, we identified 20% (9/45) of polymicrobial infection.

Conclusion

This study concludes that the RIA system alone, is noninferior to conventional reaming followed by antibiotic cement spacer in the treatment of IMN infection. However, RIA shows greater efficacy in the collection of infected medullary bone tissue, mainly in cases of infected retrograde nail of the femur.

Trial registration

ISRCTN82233198. Retroactively registered on July 29, 2019.
Standardization of early drain removal following pancreatic resection: proposal of the “Ottawa pancreatic drain algorithm”
Authors: Smith Heather , Balaa Fady K. , Martel Guillaume , Abou Khalil Jad , Bertens Kimberly A.
Published: December 2019

Background

Early drain removal after pancreatic resection is encouraged for individuals with low postoperative day 1 drain amylase levels (POD1 DA) to mitigate associated morbidity. Although various protocols for drain management have been published, there is a need to assess the implementation of a standardized protocol.

Methods

The Ottawa pancreatic drain algorithm (OPDA), based on POD1 DA and effluent volume, was developed and implemented at our institution. A retrospective cohort analysis was conducted of all patients undergoing pancreatic resection January 1, 2016-October 30, 2017, excluding November and December 2016 (one month before and after OPDA implementation).

Results

42 patients pre-implementation and 53 patients post-implementation were included in the analysis. The median day of drain removal was significantly reduced after implementation of the OPDA (8 vs. 5 days; p = 0.01). Early drain removal appeared safe with no difference in reoperation or readmission rate after protocol implementation (p = 0.39; p = 0.76). On subgroup analysis, median length of stay was significantly shorter following OPDA implementation for patients who underwent DP and did not develop a postoperative pancreatic fistula (POPF) (6 vs 10 days, p = 0.03). Although the incidence of both surgical site infection and POPF were reduced following the intervention, neither reached statistical significance (38.1 to 28.3%, p = 0.31; and 38.1 to 28.3%, p = 0.31 respectively).

Conclusions

Implementing the OPDA was associated with earlier drain removal and decreased length of stay in patients undergoing distal pancreatectomy who did not develop POPF, without increased morbidity. Standardizing drain removal may help facilitate early drain removal after pancreatic resection at other institutions.