bluuebunny/crossref_metadata_2025 huggingface dataset:
Delayed closure of macular hole secondary to Terson syndrome after vitrectomy
Authors: Sheng Yan , Sun Wen , Shen Ye
Published: August 2019

Rationale:

Macular hole (MH) is a rare complication of Terson syndrome. Delayed closure of persistent MH after pars plana vitrectomy (PPV) is occasionally reported in literature, none of them is MH secondary to Terson syndrome. We describe a case of MH secondary to Terson syndrome and delayed closure occurred after PPV, and we also study the characteristics of delayed closure of persistent MH by reviewing related literatures.

Patient concerns:

A 61-year-old man presented with vitreous hemorrhage in right eye following a subarachnoid hemorrhage due to spontaneous rupture of his right vertebral artery dissecting aneurysm. The visual acuity was hand motion in the right eye and 20/30 in the left eye. Fundus examination showed dense and diffuse vitreous hemorrhage in the right eye.

Diagnoses:

Terson syndrome was diagnosed according to his subarachnoid hemorrhage history and vitreous hemorrhages in right eye.

Interventions:

PPV combined with phacoemulsification and intraocular lens implantation was performed in his right eye, and internal limiting membrane (ILM) peeling was also performed due to a MH noted during the surgery.

Outcomes:

One week after PPV, optical coherence tomography (OCT) showed a persistent MH. Without any intervention, the MH became smaller and flattened, with the best corrected visual acuity (BCVA) improved to 30/200 at 1 month after surgery. Six months later, the MH completely closed with BCVA improved to 20/40. According to our literature review, there are 8 cases of the delayed MH closure, which includes idiopathic MH (4 eyes), traumatic MH (2 eyes), and vitreomacular traction (2 eyes). There is no report about delayed closure of MH secondary to Terson syndrome. The times for these delayed closure occurred following PPV were ranged from 1 to 28 months. Holes even with obviously raised edges after PPV may spontaneously close, just like the case presented here.

Lessons:

Delayed closure of persistent MH after PPV is rarely reported. The significance of this case is to suggest that similar patients should be monitored carefully by OCT, and additional surgery for the MH may be delayed, since delayed closure is possible. The exact mechanisms of delayed closure of persistent MH still need to be clarified.
Risk factors associated with hepatic osteopathy in HBV related cirrhosis measured by liver stiffness
Authors: Zhang Wei , Gong Hui , Su Zengcun , Zhang Xuping , Cao Shujuan
Published: August 2019

To investigate the differences in bone mineral density between patients with liver cirrhosis and healthy control, and to analyze the risk factors of hepatic osteoporosis in patients with HBV related liver cirrhosis.

A total of 189 patients with liver cirrhosis and 207 health controls were enrolled. The bone mineral density of lumbar spine and femoral neck was examined by dual energy X-ray absorptiometry. −2.0 <T value <−1.0 defined as osteopenia, T value ≤−2.0 defined as osteoporosis.

Bone mineral density in the cirrhotic group was significantly lower than that in the control group (lumbar: 1.02 ± 0.16 vs 1.08 ± 0.13, P < .001; femoral neck: 0.86 ± 0.14 vs 0.91 ± 0.14, P < .001). Both 2 groups showed a tendency that decrease bone density correlated with age and decrease body mass index (BMI). Multivariate correlation analysis showed that women (OR = 6.931, P = .002), age (OR = 1.096, P < .001), low BMI (OR = 0.874, P = .037), and high liver stiffness value (OR = 1.125, P = .046) were independent risk factors for osteopenia and low body weight (OR = 0.934, P = .006) and high liver stiffness value (OR = 1.246, P = .034) were independent risk factors for osteoporosis.

Our study shows that bone mineral density in patients with liver cirrhosis decreased significantly, especially in the elderly and low BMI patient. For HBV-related cirrhosis with risk factors, a regular bone density screening should be given, and timely intervention should be taken into consideration.
Rectal adenocarcinoma coexisting with incidentally found microscopic gastrointestinal stromal tumor
Authors: Xue Wangsheng , Li Yongbo , Wang Shuang , Yu Ke , Yu Jiaqi , Zhao Zeyun , Jiang Dan , Zhang Mingwei , Liu Tongjun , Wang Min
Published: August 2019

Rationale:

Adenocarcinoma coexists with adjacent microscopic gastrointestinal stromal tumor (micro-GIST) is rare, especially in the rectum, where the gastrointestinal stromal tumors (GISTs) have the lower incidence rate. It is easy to ignore the concurrent micro-GIST due to the untypical symptoms.

Patient concerns:

A 77-year-old male patient suffered from lower abdominal pain for 20 days and presented with per rectal bleeding for 10 days. He had the medical history of hypertension and diabetes for more than 25 years.

Diagnoses:

Endoscopy revealed that the patient had rectum adenocarcinoma and multiple rectum polyps. Besides, the gastrointestinal stromal tumor was diagnosed by the pathologist.

Interventions:

The patient underwent surgery of laparoscopic rectum resection and prophylactic ileostomy and took 6 courses of Capecitabine tablets orally.

Outcomes:

One year after surgery, the patient had no local relapse by the CT scan. However, not long after the CT examination, he died of cardiovascular disease.

Lessons:

Although micro-GIST may be noninvasive and asymptomatic, it may have the potential for transforming to malignancies. More attention should be paid to the patients diagnosed with gastrointestinal malignancy coexisting with micro-GIST.
Fetal giant right cervical cyst causing severe tracheal compression
Authors: Kang Yanming , Ma Yushan , Jiang Xiaoqin , Lin Xuemei , Zhao Fumin
Published: August 2019

Rationale:

Fetal giant cervical cyst (FGCC) is a rare congenital anomaly. Sometimes FGCC may extend into the mediastinum, and result in severe tracheal compression, which is a life-threatening event at birth.

Patient concerns:

We present a rare case of FGCC, which extended from the right neck into the superior mediastinum, and resulted in severe tracheal compression.

Diagnoses:

An FGCC was observed by ultrasonography and magnetic resonance imaging (MRI) at 27+4 weeks’ gestation (WG). Fetal MRI at 35+1 WG showed that the FGCC was 3.3 × 8.2 × 7.5 cm and extended from the right neck into the superior mediastinum. Severe tracheal compression was observed and the inside diameter of the narrowest section of tracheostenosis appeared thread-like and measured only 0.1 cm.

Interventions:

Cervical cyst reduction was performed prenatally under ultrasound guidance to alleviate the tracheal compression and maximize the chance of fetal survival 2 days before birth. At 36+3 WG, cesarean section was performed, and a female neonate was immediately delivered and intubated (3.5-mm tube) by an experienced anesthesiologist. Neonatal intralesional sclerotherapy and cystic component aspiration as guided by digital subtraction angiography were performed under general anesthesia. Anesthesia was maintained only with sevoflurane 3% in 2 L/min oxygen. Extubation was performed soon after surgery.

Outcome:

The neonate recovered uneventfully and was discharged 2 days postoperatively. After 140 days of follow-up, the neonate had recovered completely.

Lessons:

If an FGCC is suspected by abdominal ultrasound, a fetal MRI is recommended to assess the severity of tracheal compression before birth, if feasible. An anesthesiologist should assess the risk of intubation failure at birth according to those results. If fetal severe tracheal compression is detected and it may result in inability of intubation at birth, prenatal cervical cyst reduction under ultrasound guidance may be effective for alleviating tracheal compression at birth, if feasible. This could maximize the chance of fetal survival. Improvement of fetal short- and long-term outcomes is important.
A case report on an incidental discovery of congenital portosystemic shunt
Authors: Păcurar Daniela , Dijmărescu Irina , Dijmărescu Adrian Dumitru , Romaşcanu Mihai , Becheanu Cristina Adriana
Published: August 2019

Rationale:

Congenital portosystemic shunt (Abernethy malformation) is a rare entity causing the portal blood to drain directly into the systemic circulation, eluding the liver. These shunts arise through disturbances in the embryonic development.

Patient concerns:

A 9-year-old male patient was referred to our department for further evaluation of a vascular malformation which was diagnosed in another facility when the patient was 2 years old, following a routine abdominal ultrasound. The patient had no complaints and the physical examination was normal at all times.

Diagnosis:

Laboratory tests and esogastroduodenoscopy were normal. The abdominal ultrasound showed a side-to-side shunt between a short portal trunk and the inferior vena cava. A hepatic mass suggestive for focal noduar hyperplasia was seen in the left liver lobe. Abdominal angio-computed tomography (angio-CT) was performed and the ultrasonographic anomalies were confirmed. Multiple other vascular malformations were diagnosed—hepatic artery emerging from the superior mesenteric artery, with early division; hepatic veins forming a short common trunk before draining into the inferior vena cava; supranumerary right renal artery emerging from the aorta, tributary for the upper renal pole. Ecocardiography showed left superior vena cava persistence. The final diagnosis was Abernathy malformation type IB. In the meantime the patient was diagnosed with allergic asthma.

Interventions:

No surgical cure was pursued because the malformation was an incidental discovery.

Outcomes:

The patient was followed-up closely from the final diagnosis (when he was 9 years old) to present (he is currently 10 years old) with no change in his status—he remained asymptomatic.

Lessons:

Angio-CT should be the performed whenever a vascular malformation is suspected in order to establish a correct diagnosis, because portosystemic shunts carry a high risk of severe complications. Knowing that patients with portosystemic shunts may have pulmonary hypertension, respiratory complaints should be carefully evaluated—in this particular case, even though the most probable cause for the respiratory symptoms was pulmonary hypertension, it was ruled out by cardiac ultrasonography and further investigations confirmed the diagnosis of allergic asthma.
Association of C8orf4 expression with its methylation status, aberrant β-catenin expression, and the development of cervical squamous cell carcinoma
Authors: Lan Chong , Huan Da-Wei , Nie Xiao-Cui , Niu Ju-Min , Sun Jian-Hua , Huang Wen-Jing , Li Zhi-Han , Xu Hong-Tao
Published: August 2019

Chromosome 8 open reading frame 4 (C8orf4) is an activator of Wnt signaling pathway, and participates in the tumorigenesis and progression of many tumors. The expression levels of C8orf4 and β-catenin were assessed via immunohistochemical staining in 100 cervical squamous cell carcinoma (CSCC) tissues, 50 high-grade squamous intraepithelial lesions (HSILs), 50 low-grade squamous intraepithelial lesions (LSILs), and 50 normal cervical tissues. Bisulfite sequencing polymerase chain reaction analysis was used to examine the methylation status of the C8orf4 locus in CSCC and normal cervical tissues. The expression rates of C8orf4 and β-catenin were significantly higher in CSCCs or HSILs than in LSILs or normal cervical tissues (P < .05). C8orf4 expression was positively correlated with the poor differentiation of CSCCs (P = .009), and with aberrant expression of β-catenin in CSCCs (P = .002) and squamous intraepithelial lesions (P < .001). The methylation rate of C8orf4 in CSCCs was significantly lower than that in normal cervical tissues (P = .001). The Cancer Genome Atlas genomics data also confirmed that the mRNA expression of C8orf4 was positively associated with the copy number alteration of C8orf4 (correlation coefficient = 0.213, P < .001), and negatively correlated with the methylation level of C8orf4 (correlation coefficient = −0.408, P < .001). In conclusion, the expressions of C8orf4 and β-catenin were synergistically increased in CSCCs and HSILs and higher than those in LSILs and normal cervical tissues. The methylation level of C8orf4 is decreased in CSCCs and is responsible for the increased expression of C8orf4.
Assessing the Expression of Aquaporin 3 Antigen-Recognition Sites in Oral Squamous Cell Carcinoma
Authors: Udompatanakorn Chatchaphan , Yada Naomi , Matsuo Kou
Published: August 2019

Aquaporin 3 (AQP3) serves as a water and glycerol transporter facilitating epithelial cell hydration. Recently, the involvement of AQP3 in cancers has been reported. However, the immunohistochemical expression of AQP3 in carcinomas remains controversial. We hypothesized that differences in aquaporin 3 antigen recognition (AQP3 AR) may influence their expressions. Thus, our study aimed to assess the immunostaining patterns of 3 AQP3 AR sites in oral squamous cell carcinoma (OSCC) and to compare the adjacent areas of high-grade epithelial dysplasia (HG-ED) and normal oral mucosa (NOM). The study group included formalin-fixed OSCC samples (n=51) with adjacent regions of HG-ED (n=12) and NOM (n=51). The tissues were stained with anti-AQP3 antibodies (AR sites at amino acid (AA) 250-C terminus, AA180-228, and N terminus AA1-80) by immunohistochemistry. Our results showed that strong membranous immunostaining was observed for AQP3 AR sites at the AA250-C terminus and AA180-228 in all the samples for NOM and weak AQP3 immunostaining for both the AR sites in all the 12 samples for HG-ED. The invasive front of OSCC samples showed that AQP3 AR at the AA250-C terminus decreased in 42/51 samples (82.4%) and AA180-228 in 47/51 samples (92.2%). Conversely, in the AQP3 AR site at N terminus AA1-80, all samples of the NOM showed negative or slightly positive staining in the cytoplasm of the lower layers. AQP3 expression was increased in 12/12 cases (100%) and 46/51 cases (90.2%) in the HG-ED and invasive front of OSCC, respectively. AQP3 may be used as a biomarker for detecting malignant transformations. AQP3 AR site differences influence their immunohistochemical expression in OSCC.
Control of Nasal Tip Position: Quantitative Assessment of Columellar Strut versus Caudal Septal Extension Graft
Authors: Sawh-Martinez Rajendra , Perkins Kevin , Madari Sarika , Steinbacher Derek M.
Published: August 2019

Background:

Control and maintenance of nasal tip position are critical in rhinoplasty. Two frequent methods of exerting tip control are columellar strut and caudal septal extension graft. However, no quantitative data exist comparing the two methods over time. The purpose of this study was to analyze maintenance of tip projection and rotation following either columellar strut or septal extension graft.

Methods:

A retrospective cohort study of patients undergoing rhinoplasty was reviewed. Three-dimensional photogrammetric evaluation of patients with either columellar strut or septal extension graft to increase tip projection was performed. Anthropometric points were analyzed in a blinded fashion. Outcome variables were tip projection, nasal length, the Goode ratio, and tip rotation. Results were stratified based on technique and compared statistically.

Results:

One hundred six patients were included. Overall, 66 percent were female, with an average age of 34.5 years. A columellar strut was used in 42 percent of cases (n = 45), and a septal extension graft was used in 57 percent (n = 61). Analysis showed greater maintenance of tip rotation over time with the septal extension graft compared with the columellar strut [−1.01 percent change (p = not significant versus −5.08 percent change (p = 0.009)]. Tip projection, nasal length, and the Goode ratio decreased over time for both groups, but the differences were not statistically different.

Conclusions:

Nasal tip projection and rotation appear to decrease from the immediate postoperative position. In this study, both septal extension graft and columellar strut exhibit similar changes in tip projection with time; however, septal extension graft is better able to preserve tip rotation compared with the columellar strut.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, III.
Significant Radiation Dose Reduction Using a Novel Angiography Platform in Patients Undergoing Cryoballoon Pulmonary Vein Isolation
Authors: Schmidt Martin , Tesche Christian , Hapfelmeier Alexander , Finsterer Sebastian , Valassis Gregorius , Ebersberger Ullrich , Schlüter Mathis , Ziegler Martin , Kraemer Bjoern F.
Published: August 2019

Objectives:

Cryoballoon pulmonary vein isolation (cPVI) in patients with atrial fibrillation requires fluoroscopic guidance, causing a relevant amount of radiation exposure. Strategies to reduce radiation exposure in electrophysiologic procedures and specifically cPVI are of great importance. The aim of this study was to evaluate a possible reduction of radiation dose using the novel Azurion 7 F12 x-ray system compared with its predecessor Allura FD10.

Methods:

In February 2017, the Philips Azurion angiography system was introduced, combining the Allura Clarity radiation dose reduction technology with a more powerful generator, improved image resolution, and a large screen display. In 173 patients undergoing cPVI by a single experienced operator in our institution between December 2016 and April 2018, dose area products (cGy×cm2) and image quality were compared using Azurion 7 F12 or Allura FD10 angiography system.

Results:

A significant reduction in total radiation dose expressed as a dose area products of 524 (332; 821) cGy×cm2 on the Allura system compared with 309 (224; 432) cGy×cm2 on the Azurion system was observed (P<0.001). The number of imaging scenes recorded were 14.7 versus 13.9, and mean overall imaging quality scores (grading 4.85±0.4 with Azurion vs. 4.80±0.4 with Allura, P=0.38) and scores based on specific quality parameters were similar in both groups.

Conclusion:

Use of the new Azurion 7 F12 angiography system substantially reduced radiation doses compared with the previous generation reference system, Allura Clarity, without compromising imaging quality in patients undergoing cryoballoon pulmonary vein isolation.
LSD1-mediated enhancer silencing enables endocrine cell development through attenuation of retinoic acid signalling
Authors: Vinckier Nicholas K. , Patel Nisha A. , Wang Allen , Wang Jinzhao , Shih Hung-Ping , Wang Jianxun , Jhala Ulupi S. , Rosenfeld Michael G. , Benner Christopher W. , Sander Maike
Published: August 2019

Developmental progression depends on temporally defined changes in gene expression mediated by transient exposure of lineage intermediates to signals in the progenitor niche. To identify a possible contribution of cell-intrinsic epigenetic mechanisms to signal-induced transcriptional responses, we manipulated the signalling environment and activity of the histone demethylase LSD1 during stepwise differentiation of gut tube intermediates into pancreatic endocrine cells. Analysis of enhancer and transcriptome landscapes revealed that lineage progression and endocrine cell differentiation requires LSD1-mediated silencing of transiently active retinoic acid (RA)-induced enhancers. In the absence of LSD1, early RA-responsive enhancers remain partially active despite RA removal, resulting in perduring expression of RA-induced genes, and failure to progress in development. Our findings identify LSD1-mediated enhancer silencing as a cell-intrinsic epigenetic feedback mechanism by which the duration of the transcriptional response to a developmental signal is limited. Given LSD1’s requirement in numerous developmental contexts, the here-described mechanism would be broadly relevant.
Telomeric Double Strand Breaks Facilitate Formation of 5’ C-Rich Overhangs in G1 Human Cells
Authors: Nelson Christopher B , Al Turki Taghreed M , Taylor Lynn , Maranon David G , Muraki Keiko , Murnane John P. , Bailey Susan M
Published: August 2019

Telomeres are repetitive nucleoprotein complexes that protect chromosomal termini and prevent them from activating an inappropriate DNA damage response (DDR). Here, we characterized the human cellular response to targeted telomeric DSBs in telomerase positive and telomerase-independent alternative lengthening of telomeres (ALT) cells, specifically in G1. Telomeric DSBs in G1 human cells elicited early signatures of a DDR, however, localization of 53BP1, an important regulator of resection at broken ends, was not observed at telomeric break sites. Consistent with this finding and previously reported repression of classical nonhomologous end-joining (c-NHEJ) at telomeres, evidence for c-NHEJ was also lacking. Likewise, no evidence of homologous recombination (HR)-dependent repair of telomeric DSBs in G1 was observed. Rather, and supportive of rapid truncation events, telomeric DSBs in G1 human cells facilitated formation of extensively resected tracks of 5’ C-rich telomeric single-stranded (ss)DNA, a previously proposed marker of the recombination dependent ALT pathway. Indeed, induction of telomeric DSBs in human ALT cells also resulted in significant increases in 5’ C-rich (ss)telomeric DNA in G1, which rather than RPA, were bound by the complementary telomeric RNA, TERRA. These results suggest that targeting TERRA-mediated protection at damaged telomeres may represent a promising therapeutic strategy, particularly against ALT-positive cancers.
Alpha oscillations in the human brain implement distractor suppression independent of target selection
Authors: Wöstmann Malte , Alavash Mohsen , Obleser Jonas
Published: August 2019

In principle, selective attention is the net result of target selection and distractor suppression. The way in which both mechanisms are implemented neurally has remained contested. Neural oscillatory power in the alpha frequency band (~10 Hz) has been implicated in the selection of to-be-attended targets, but there is lack of empirical evidence for its involvement in the suppression of to-be-ignored distractors. Here, we use electroencephalography (EEG) recordings of N = 33 human participants (males and females) to test the pre-registered hypothesis that alpha power directly relates to distractor suppression and thus operates independently from target selection. In an auditory spatial pitch discrimination task, we modulated the location (left vs right) of either a target or a distractor tone sequence, while fixing the other in the front. When the distractor was fixed in the front, alpha power relatively decreased contralaterally to the target and increased ipsilaterally. Most importantly, when the target was fixed in the front, alpha lateralization reversed in direction for the suppression of distractors on the left versus right. These data show that target-selection–independent alpha power modulation is involved in distractor suppression. While both lateralized alpha responses for selection and for suppression proved reliable, they were uncorrelated and distractor-related alpha power emerged from more anterior, frontal cortical regions. Lending functional significance to suppression-related alpha oscillations, alpha lateralization at the individual, single-trial level was predictive of behavioral accuracy. These results fuel a renewed look at neurobiological accounts of selection-independent suppressive filtering in attention.

Significance statement

Although well-established models of attention rest on the assumption that irrelevant sensory information is filtered out, the neural implementation of such a filter mechanism is unclear. Using an auditory attention task that decouples target selection from distractor suppression, we demonstrate that two sign-reversed lateralized alpha responses reflect target selection versus distractor suppression. Critically, these alpha responses are reliable, independent of each other, and generated in more anterior, frontal regions for suppression versus selection. Prediction of single-trial task performance from alpha modulation after stimulus onset agrees with the view that alpha modulation bears direct functional relevance as a neural implementation of attention. Results demonstrate that the neurobiological foundation of attention implies a selection-independent alpha oscillatory mechanism to suppress distraction.
Metabolic rate is negatively linked to adult survival but does not explain latitudinal differences in songbirds
Authors: Boyce Andy J. , Mouton James C. , Lloyd Penn , Wolf Blair O. , Martin Thomas E.
Published: August 2019

Survival rates vary dramatically among species and predictably across latitudes, but causes of this variation are unclear. The rate of living hypothesis posits that physiological damage from metabolism causes species with faster metabolic rates to exhibit lower survival rates. However, whether increased survival commonly observed in tropical and south temperate latitudes is associated with slower metabolic rate remains unclear. We compared metabolic rates and annual survival rates across 46 species that we measured, and 147 species from literature data across northern, southern, and tropical latitudes. High metabolic rates were associated with lower survival but latitude had substantial direct effects on survival independent of metabolism. The inability of metabolic rate to explain latitudinal variation in survival suggests 1) that species may evolve physiological mechanisms that mitigate physiological damage from cellular metabolism, and 2) a larger role of extrinsic environmental, rather than intrinsic metabolic, causes of latitudinal differences in mortality.
The Effects of Genotype × Phenotype Interactions on Silver Nanoparticle Toxicity in Organotypic Cultures of Murine Tracheal Epithelial Cells
Authors: Nicholas Tyler P. , Haick Anoria K. , Workman Tomomi W. , Griffith William C. , Nolin James D. , Kavanagh Terrance J. , Faustman Elaine M. , Altemeier William A.
Published: August 2019

Silver nanoparticles (AgNP) are used in multiple applications but primarily in the manufacturing of antimicrobial products. Previous studies have identified AgNP toxicity in airway epithelial cells, but noin vitrostudies to date have used organotypic cultures as a high-contentin vitromodel of the conducting airway to characterize the effects of interactions between host genetic and acquired factors, or gene × phenotype interactions (G×P), on AgNP toxicity. In the present study, we derived organotypic cultures from primary murine tracheal epithelial cells (MTEC) to characterize nominal and dosimetric dose-response relationships for AgNP-induced barrier dysfunction, glutathione (GSH) depletion, reactive oxygen species (ROS) production, lipid peroxidation, and cytotoxicity across two genotypes (A/J and C57BL/6J mice), two phenotypes (“Normal” and “Type 2 [T2]-Skewed”), and two exposures (an acute exposure of 24 h and a subacute exposure of 4 hours, every other day, over 5 days [5×4 h]). We characterized the “T2-Skewed” phenotype as anin vitromodel of chronic respiratory diseases, which was marked by increased sensitivity to AgNP-induced barrier dysfunction, GSH depletion, ROS production, lipid peroxidation, and cytotoxicity, suggesting that asthmatics are a sensitive population to AgNP exposures in occupational settings. This also suggests that exposure limits, which should be based upon the most sensitive population, should be derived usingin vitroandin vivomodels of chronic respiratory diseases. This study highlights the importance of considering dosimetry as well as G×P effects when screening and prioritizing potential respiratory toxicants. Suchin vitrostudies can be used to inform regulatory policy aimed at special protections for all populations.
A Mac2-positive progenitor-like microglial population survives independent of CSF1R signaling in adult mouse brain
Authors: Zhan Lihong , Sohn Peter Dongmin , Zhou Yungui , Li Yaqiao , Gan Li
Published: August 2019

Microglia are the resident myeloid cells in the central nervous system (CNS). The majority of microglial population relies on Csf1r signaling for survival and maintenance. However, a small subset of microglia in the murine brain can survive without Csf1r signaling, and reestablishes homeostasis after Csf1r signaling returns. Using single-cell RNA-seq, we characterized the heterogeneous microglial populations under Csf1r inhibition, including microglia lacking homeostatic markers and populations with elevated markers of monocytes, granulocytes and dendritic cells. Importantly, Mac2 is distinctively expressed in a subset of Csf1r-independent microglia cells, which were highly proliferative and shared striking similarities with those of microglial progenitors in yolk sac and early embryos. Lineage-tracing revealed that the Mac2+ population is of microglial origin and does not come from periphery monocytes. In non-treated mouse brains, Mac2+ microglia exhibited progenitor transcriptomic signature indistinguishable from those survived csf1r inhibition, supporting Mac2+ progenitor-like cells are present among homeostatic microglia.
Non-apoptotic caspase activation sustains ovarian somatic stem cell functions by modulating Hedgehog-signalling and autophagy
Authors: Galasso Alessia , Iakovleva Daria , Baena-Lopez Luis Alberto
Published: August 2019

There is increasing evidence associating the activity of caspases with the regulation of basic cellular functions beyond apoptosis. Accordingly, the dysregulation of these novel non-apoptotic functions often sits at the origin of neurological disorders, metabolic defects, autoimmunity, and cancer. However, the molecular interplay between caspases and the signalling networks active in non-apoptotic cellular scenarios remains largely unknown. Our work show that non-apoptotic caspase activation is critical to modulate Hedgehog-signalling and autophagy in ovarian somatic cells from bothDrosophilaand humans under moderate stress. We also demonstrate that these novel caspase functions are key to sustain stem cell proliferation and differentiation without inducing apoptosis. Finally, we molecularly link these caspase-dependent effects to the fine-tuning of the Hedgehog-receptor, Patched. Together, these findings confer a pro-survival role to the caspases, as opposed to the widely held apoptotic function assigned to these enzymes.
Evolution of plasticity in production and transgenerational inheritance of small RNAs under dynamic environmental conditions
Authors: Silva Willian T.A.F. , Otto Sarah P. , Immler Simone
Published: August 2019

In a changing environment, small RNAs (sRNAs) play an important role in the post-transcriptional regulation of gene expression and can vary in abundance depending on the conditions experienced by an individual (phenotypic plasticity) and its parents (non-genetic inheritance). Many sRNAs are unusual in that they can be produced in two ways, either using genomic DNA as the template (primary sRNAs) or existing sRNAs as the template (secondary sRNAs). Thus, organisms can evolve rapid plastic responses to their current environment by adjusting the amplification rate of sRNA templates. sRNA levels can also be transmitted transgenerationally by the direct transfer of either sRNAs or the proteins involved in amplification. Theory is needed to describe the selective forces acting on sRNA levels, accounting for the dual nature of sRNAs as regulatory elements and templates for amplification and for the potential to transmit sRNAs and their amplification agents to offspring. Here, we develop a model to study the dynamics of sRNA production and inheritance in a fluctuating environment. We tested the selective advantage of mutants capable of sRNA-mediated phenotypic plasticity within resident populations with fixed levels of sRNA transcription. Even when the resident was allowed to evolve an optimal constant rate of sRNA production, plastic amplification rates capable of responding to environmental conditions were favored. By contrast, mechanisms allowing sRNA transcripts or amplification agents to be inherited were favored primarily when parents and offspring face similar environments and when selection acts before the optimal level of sRNA can be reached within the organism. Our study provides a clear set of testable predictions for the evolution of sRNA-related mechanisms of phenotypic plasticity and transgenerational inheritance.
Secondary evolve and re-sequencing: an experimental confirmation of putative selection targets without phenotyping
Authors: Burny Claire , Nolte Viola , Nouhaud Pierre , Dolezal Marlies , Schlötterer Christian
Published: August 2019

Evolve and re-sequencing (E&R) studies investigate the genomic responses of adaptation during experimental evolution. Because replicate populations evolve in the same controlled environment, consistent responses to selection across replicates are frequently used to identify reliable candidate regions that underlie adaptation to a new environment. However, recent work demonstrated that selection signatures can be restricted to one or a few replicate(s) only. These selection signatures frequently have a weak statistical support, and given the difficulties of functional validation, additional evidence is needed before considering them as candidates for functional analysis. Here, we introduce an experimental procedure to validate candidate loci with weak or replicate-specific selection signature(s). Crossing an evolved population from a primary E&R experiment to the ancestral founder population reduces the frequency of candidate alleles that have reached a high frequency. We hypothesize that genuine selection targets will experience a repeatable frequency increase after the mixing with the ancestral founders if they are exposed to the same environment (secondary E&R experiment). Using this approach, we successfully validate two overlapping selection targets, which showed a mutually exclusive selection signature in a primary E&R experiment of Drosophila simulans adapting to a novel temperature regime. We conclude that secondary E&R experiments provide a reliable confirmation of selection signatures that are either not replicated or show only a low statistical significance in a primary E&R experiment. Such experiments are particularly helpful to prioritize candidate loci for time-consuming functional follow-up investigations.
Carbon dots for efficient siRNA delivery and gene silencing in plants
Authors: Schwartz Steven. H. , Hendrix Bill , Hoffer Paul , Sanders Rick A. , Zheng Wei
Published: August 2019

The Initiation of RNA interference (RNAi) by topically applied double stranded RNA (dsRNA) has potential applications for plant functional genomics, crop improvement and crop protection. The primary obstacle for the development of this technology is efficient delivery of RNAi effectors. The plant cell wall is a particularly challenging barrier to the delivery of macromolecules. Many of the transfection agents that are commonly used with animal cells produce nanocomplexes that are significantly larger than the size exclusion limit of the plant cell wall. Utilizing a class of very small nanoparticles called carbon dots, a method of delivering siRNA into the model plantNicotiana benthamianaand tomato is described. Low-pressure spray application of these formulations with a spreading surfactant resulted in strong silencing ofGFPtransgenes in both species. The delivery efficacy of carbon dot formulations was also demonstrated by silencing endogenous genes that encode two sub-units of magnesium chelatase, an enzyme necessary for chlorophyll synthesis. The strong visible phenotypes observed with the carbon dot facilitated delivery were validated by measuring significant reductions in the target gene transcript and/or protein levels. Methods for the delivery of RNAi effectors into plants, such as the carbon dot formulations described here, could become valuable tools for gene silencing in plants with practical applications in plant functional genomics and agriculture.
High-resolution QTL mapping with Diversity Outbred mice identifies genetic variants that impact gut microbiome composition
Authors: Schlamp Florencia , Zhang David Y , Beltrán Juan Felipe , Cosgrove Elissa J , Simecek Petr , Edwards Matthew , Goodrich Julia K , Ley Ruth E , Pack Allan , Churchill Gary A , Clark Andrew G
Published: August 2019

The composition of the gut microbiome is impacted by a complex array of factors, from nutrient composition and availability, to physical factors like temperature, pH, and flow rate, as well as interactions among the members of the microbial community. Many of these factors are affected by the host, raising the question of how host genetic variation impacts microbiome composition. Though human studies confirm this type of role for host genetics, its overall importance is still a subject of debate and remains difficult to study. The mouse model, by allowing the strict control of genetics, nutrition, and other environmental factors, has provided an excellent opportunity to extend this work, and the Diversity Outbred (DO) mice in particular present a chance to pinpoint host genetic variants that influence microbiome composition at different levels of generality. Here, we apply 16S rRNA gene sequencing to fecal samples of 247 DO male mice to estimate heritability and perform taxon-specific QTL mapping of microbial relative abundances revealing an increasingly heterogeneous picture of host function and microbial taxa at the host-microbiome interface. We present the first report of significant heritability of phylum Tenericutes in mice, and find novel QTL-spanning genes involved in antibacterial pathways, immune and inflammatory disease, and lipid metabolism.
Machine Learning Models of Breast Cancer Risk Prediction
Authors: Islam Md. Mohaimenul , Poly Tahmina Narin
Published: August 2019

Breast cancer is the most common cancer in women both in the developed and less developed world. Early detection based on clinical features can greatly increase the chances for successful treatment. Our goal was to construct a breast cancer prediction model based on machine learning algorithms. A total of 10 potential clinical features like age, BMI, glucose, insulin, HOMA, leptin, adiponectin, resistin, and MCP-1 were collected from 116 patients. In this report, most commonly used machine learning model such as decision tree (DT), random forest (RF), K-nearest neighbors (KNN), support vector machine (SVM), logistic regression (LR), and artificial neural network (ANN) models were tested for breast cancer prediction. A repeated 10-fold cross-validation model was used to rank variables on the randomly split dataset. The accuracy of DT, RF, SVM, LR, ANN, and KNN was 0.71, 0.71, 0.77, 0.80, 0.81, and 0.86 respectively. However, The KNN model showed most higher accuracy with area under receiver operating curve, sensitivity, and specificity of 0.95, 0.80, 0.91. Therefore, identification of breast cancer patients correctly would create care opportunities such as monitoring and adopting intervention plans may benefit the quality of care in long-term.
Development of the mandibular curve of Spee and maxillary compensating curve: A finite element model
Authors: Marshall Steven D. , Kruger Karen , Franciscus Robert G. , Southard Thomas E.
Published: August 2019

The curved planes of the human dentition seen in the sagittal view, the mandibular curve of Spee and the maxillary compensating curve, have clinical importance to modern dentistry and potential relevance to the craniofacial evolution of hominins. However, the mechanism providing the formation of these curved planes is poorly understood. To explore this further, we use a simplified finite element model, consisting of maxillary and mandibular “blocks”, developed to simulate tooth eruption, and forces opposing eruption, during simplified masticatory function. We test our hypothesis that curved occlusal planes develop from interplay between tooth eruption, occlusal load, and mandibular movement.

Our results indicate that our simulation of rhythmic chewing movement, tooth eruption, and tooth eruption inhibition, applied concurrently, results in a transformation of the contacting maxillary and mandibular block surfaces from flat to curved. The depth of the curvature appears to be dependent on the radius length of the rotating (chewing) movement of the mandibular block. Our results suggest mandibular function and maxillo-mandibular spatial relationship may contribute to the development of human occlusal curvature.
Intestinal parasitic infection among household contacts of primary cases, a comparative cross-sectional study
Authors: Feleke Berhanu Elfu , Beyene Melkamu Bedimo , Feleke Teferi Elfu , Jember Tadesse Hailu , Abera Bayeh
Published: August 2019

Background

Intestinal parasitic infection affects 3.5 billion people in the world and mostly affecting the low socio-economic groups. The objectives of this research were to estimate the prevalence and determinants of intestinal parasitic infection among family members of known intestinal parasite infected patients.

Methods and materials

A comparative cross-sectional study design was implemented in the urban and rural settings of mecha district. The data were collected from August 2017 to March 2019 from intestinal parasitic infected patient household members. Epi-info software was used to calculate the sample size, 4531 household members were estimated to be included. Data were collected using interview technique and colleting stool samples from each household contact of intestinal parasite patients. Descriptive statistics were used to estimate the prevalence of intestinal parasites among known contacts of intestinal parasites patients/family members. Binary logistic regression was used to identify the determinant factors of intestinal parasitic infection among family members.

Results

The prevalence of intestinal parasite among household contacts of parasite-infected family members was 86.14 % [95% CI: 86.14 % - 87.15 %].Hookwormparasitic infection was the predominant type of infection (18.8%). Intestinal parasitic infection was associated with sex, environmental sanitation, source of water, habit of playing with domestic animals, the presence of chicken in the house, the presence of household water filtering materials, overcrowding, personal hygiene, residence, and substandard house, role in the household, source of light for the house, floor materials, trimmed fingernails, family size, regular hand washing practice, barefoot.

Conclusion

The prevalence of intestinal parasites was high among household contacts of primary confirmed cases.
A Signal Demodulation-based Method for the Early Detection of Cheyne-Stokes Respiration
Authors: Guyot Pauline , Djermoune El-Hadi , Chenuel Bruno , Bastogne Thierry
Published: August 2019

Cheyne-Stokes respiration (CSR) is a sleep-disordered breathing characterized by recurrent central apneas alternating with hyperventilation exhibiting a crescendo-decrescendo pattern of tidal volume. This respiration is reported in patients with heart failure, stroke or damage in respiratory centers. It increases mortality for patients with severe heart failure as it has adverse impacts on the cardiac function. Early stage of CSR, also called periodic breathing, is often undiagnosed as it only provokes hypopneas instead of apneas, which are much more difficult to detect. This paper demonstrates the proof of concept of a new method devoted to the early detection of CSR. The proposed approach relies on a signal demodulation technique applied to ventilation signals measured on 15 patients with chronic heart failure whose respiration goes from normal to severe CSR. Based on a modulation index and its instantaneous frequency, oscillation zones are detected and classified into three categories: CSR, periodic breathing and no abnormal pattern. The modulation index is used as an efficient biomarker to quantify the severity of the pathology for each patient. Results show high correlation with experts’ annotations with sensitivity and specificity values of 87.1% and 89.8% respectively. A final decision leads to a classification which is confirmed by the experts’ conclusions.
Predictive model for corrosion hazard of buried metallic structure caused by stray current in the subway
Authors: Wang Chengtao , Li Wei , Wang Yuqiao , Yang Xuefeng , Xu Shaoyi , Li Kunpeng , Zhao Yunyun
Published: August 2019

Purpose

The purpose of this paper is to predict quantitative level of stray current leaking to the buried metallic structure by establishing convolution neural network (CNN) model.

Design/methodology/approach

First, corrosion experimental system of buried metallic structure is established. The research object of this paper is the polarization potential within 110 min, CNN model is used to predict the quantitative level of stray current leakage using the data from corrosion experimental system further. Finally, results are compared with the method using BP neural network.

Findings

Results show that the CNN model has better predictive effect and shorter prediction time than the BP model, the accuracy of which is 82.5507 per cent, and the prediction time is shortened by more than 10 times.

Originality/value

The established model can be used to forecast the level of stray current leakage in the subway system effectively, which provides a new theoretical basis for evaluating the stray current corrosion hazard of buried metallic structure.
Festival loyalty to a South African literary arts festival: action speaks louder than words!
Authors: Kruger Martinette
Published: August 2019

Purpose

The purpose of this paper is to fill the gap in the literature by focusing on the profile and loyalty of visitors to a literary arts festival in South Africa. In addition, this research advocates that festivals can influence visitors’ supplementary behavioural intentions and actions beyond loyalty in the form of literary arts appreciation, purchases and tourism.

Design/methodology/approach

A visitor survey was conducted at one of the oldest literary arts festivals in the country where a total of 391 completed self-administered questionnaires were obtained. The statistical analyses comprised three factor analyses (motives to attend the festival, satisfaction with the festival offering elements and behavioural intentions) as well as structural equation modelling, to establish the relationship between the motives, evaluation of the “festivalscapes”, behavioural intentions and loyalty.

Findings

The findings confirmed that literary arts festival loyalty is the principle behavioural intention that will occur after attending a literary arts festival. However, the results demonstrated that literary arts festivals also have the potential to increase and stimulate supplementary behavioural intentions in the form of greater awareness of the arts, increased purchasing behaviour of literary works, increased travel to support the literary arts and greater personal involvement.

Practical implications

Festivals, irrespective of the art form that they showcase, therefore, play a significant role in encouraging and increasing purchasing behaviour, which is vital to the viability and continuation of the arts industry.

Originality/value

This is one of the first studies to research the literary arts festival market in South Africa, thereby making a distinct contribution by expanding the literature on the needs of this neglected market and the aspects that influence loyalty to these types of festivals.