bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBackgroundInfertility 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.MethodsFetal 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.ResultsMSY2 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.ConclusionsWe 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

AbstractBackgroundNeuraminidase (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.MethodsMouse 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).ResultsIn 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.ConclusionsNA 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

Abstract
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

AbstractBackgroundThe 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.ResultsHere, 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.ConclusionsExplanations 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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundSchaaf-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.ResultsTruncating 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.ConclusionsSYS 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

Abstract
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

Abstract
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.