bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Short-Term Efficacy Between Endoscopic Submucosal Tunnel Dissection and Endoscopic Submucosal Dissection in Treatment of Wide Esophageal Squamous Cell Carcinoma of Early Stage
Authors: Li Yuan , Wang Keyi , Shi Yanyan , Zhu Jin , Cui Rongli , Zhang Hejun , Ding Shigang
Published: September 2019

Goal:

The goal of this study was to compare the efficacy and safety of endoscopic submucosal tunnel dissection (ESTD) with endoscopic submucosal dissection (ESD) for the removal of early-stage esophageal squamous cancer wider than or equal to one half the circumference of the esophagus.

Background:

Although ESD has been successfully applied for resection of early-stage esophageal cancer, there are still technical challenges and postoperative stenosis when it is applied to treat large lesions.

Patients and Methods:

A total of 40 patients with early-stage esophageal cancer wider than or equal to one half its circumference were enrolled in this study and randomly assigned to an ESTD or ESD group for treatment of esophageal superficial squamous cell carcinoma. All of the patients received oral steroids after endoscopic dissection. We then compared the 2 groups in terms of average operating time, dissection speed, en bloc resection rate, R0 resection rate, and complications during a 1-year follow-up period.

Results:

The dissection speed in the ESTD group was significantly faster than that in the ESD group (P=0.047). There were no significant differences in operating time, en bloc resection rates, or R0 resection rates between the ESTD and ESD group (P=0.319, 1.000, 1.000, respectively). There were also no significant differences in perforation, bleeding, or stenosis rates between the ESTD and ESD group (P=1.000, 0.748, 1.000, respectively).

Conclusion:

Both ESTD and ESD are safe and effective therapies for early-stage esophageal cancer wider than or equal to one half the esophageal circumference. The dissection speed of ESTD is faster than that of ESD.
Tracing Metacognition in Psychotherapy
Authors: Arnon-Ribenfeld Nitzan , Atzil-Slonim Dana , Bar-Kalifa Eran , Silber Yosef , Fisher Hadar , Peri Tuvia , Lysaker Paul H. , Hasson-Ohayon Ilanit
Published: September 2019

Deficits in metacognition have often been identified as a central feature in various forms of psychopathology. The current study explores changes in metacognition and symptoms during the process of psychodynamic-oriented psychotherapy conducted in a community setting among people with diverse psychological challenges. We examined the associations between metacognition and symptoms at both the within-client and the between-clients level. Nine good-outcome and nine poor-outcome cases of psychodynamic treatment were analyzed. In terms of metacognitive abilities, results showed that clients who were part of the good-outcome group had higher levels of decentration than did clients who were part of the poor-outcome group. In addition, clients' ability to understand the other's mind improved significantly only for clients in the good-outcome group. Furthermore, sessions in which clients' self-reflectivity was higher were followed by increased symptom levels (in the next session) beyond group (poor or good outcome group). Clinical implications regarding the improvement of metacognitive abilities and their associations with outcome measures are discussed.
Patterns, Predictors, and Prognostic Validity of Persistent Complex Bereavement Disorder Symptoms in Recently Bereaved Adults
Authors: Boelen Paul A. , Smid Geert E. , Mitima-Verloop Huibertha B. , de Keijser Jos , Lenferink Lonneke I.M.
Published: September 2019

Persistent complex bereavement (PCBD) was entered to DSM-5. No studies have yet examined the nature, prevalence, prognostic validity, and underlying mechanisms of PCBD symptom patterns in recently bereaved people. Knowledge on these issues could improve the early identification and treatment of disturbed grief. Latent class analysis was used to identify subgroups characterized by different PCBD symptom patterns among recently (≤6 months) bereaved adults (n = 476). In a subgroup (n = 251), we assessed associations of class membership with PCBD severity and functional impairment assessed 3 years later. Associations between class membership and sociodemographic and cognitive-behavioral variables were also examined. We identified a resilient (50.0%), separation distress (36.1%), and high PCBD symptoms (13.9%) class. Class membership had prognostic value as evidenced by associations with PCBD severity and functional impairment assessed 3 years later. Deaths of partners/children, unexpectedness of the loss, and maladaptive cognitions and avoidance behaviors were also associated with membership of the pervasive symptom classes.
Facilitating the Delivery of Cognitive Remediation in First-Episode Psychosis
Authors: Moura Bernardo Melo , Avila Alessia , Chendo Inês , Frade Patrícia , Barandas Rita , Vian João , Croca Marta , Roberto Alice , Almeida Carolina , Antunes Filipa , Linhares Ludgero , Crawford Joana , Ferreira Carla , Santos Jennifer , Abreu Manuela , Levy Pedro , Figueira Maria Luísa , Mendes Tiago
Published: September 2019

We explored the adherence to a home-delivered, computer-based, cognitive remediation protocol in a first-episode psychosis outpatient cohort. Seventeen patients underwent a cognitive training protocol for 6 months using an online platform accessible from their home under the supervision of a qualified neuropsychologist. Neuropsychological, psychopathological, and functional data were collected at baseline and postintervention, whereas qualitative appraisal of the intervention was assessed monthly. Overall, participants' evaluation of the program was positive. This was reflected in a good adherence rate with 12 (70%) of 17 patients completing 80% of the prescribed sessions. Exploratory analysis revealed significant improvements in sustained attention (p = 0.020) and verbal memory (p = 0.018). A decrease in negative symptoms and an improvement on the Clinical Global Impression were also found (p = 0.009). We believe these are encouraging results to further explore the adopted delivery approach, which could facilitate access to cognitive training earlier and to a larger group of patients.
The Genomic and Molecular Pathology of Prostate Cancer: Clinical Implications for Diagnosis, Prognosis, and Therapy
Authors: Faisal Farzana A. , Lotan Tamara L.
Published: September 2019

Prostate cancer (PCa) is the most common noncutaneous malignancy affecting American men and the second most common cause of cancer death. The traditional risk classification schemes for PCa are limited due to the vast clinical and molecular heterogeneity of the disease. Fortunately, recent advancements in sequencing technologies have provided us with valuable insight into the genomics of PCa. To date, a wide array of recurrent genomic alterations in PCa have been identified. Incorporating these distinct molecular subtypes of PCa into prediction models provides opportunities for improved risk stratification and ultimately better patient outcomes. In this review, we summarize the key molecular subtypes of PCa and focus on those genomic alterations that have clinical implications for diagnosis, prognosis, and therapeutic response.
The Effect of Stabilization Exercises Along With Self-care Training on Transverse Abdominal Activity, Pain, and Disability in Mothers With Low Back Pain Having Children With Cerebral Palsy
Authors: Ahmadizadeh Zahra , Ehsani Fatemeh , Samaei Syed Afshin , Mirmohammadkhani Majid
Published: September 2019

Objective

Many mothers of children with cerebral palsy experience low back pain, so the purpose of this study was to investigate the effect of stabilization exercises along with self-care training on transverse abdominal muscle activity, pain, disability, and depression in them.

Design

In this single-blinded randomized clinical trial, 32 mothers with cerebral palsy children were selected were randomly divided into two groups. Both groups received self-care training individually. For the experimental group, in addition to the self-care training, 24 sessions of stabilization exercises were held. Outcome measures included visual analog scale, Roland-Morris Disability Questionnaire, Persian version of Beck Depression Inventory-II, and ultrasonography.

Results

In the experimental group, the transverse abdominal muscle activity during abdominal hollowing exercises was significantly increased (P < 0.05). There was no significant difference between the two groups in pain, disability, and depression (P > 0.05).

Conclusions

Stabilization exercises could improve the voluntary activity of transverse abdominal muscle of mothers of children with cerebral palsy.
Logistic Regression Analysis of Risk Factors for Intracranial Infection After Multiple Traumatic Craniotomy and Preventive Measures
Authors: Yao Jing , Liu Dong
Published: September 2019

Background and Objective:

The aim of this study was to study the risk factors of intracranial infection after traumatic craniotomy in multiple trauma to provide references for clinical prevention and control of intracranial infection.

Methods:

A total of 34 multiple trauma patients treated with craniotomy and complicated with intracranial infection from February 2012 to December 2016 in the department of neurosurgery of our hospital were selected as infection group, and 60 multiple trauma patients who had not been infected after craniotomy during the same period were selected as control group. Related risk factors were screened by univariate analysis at first and analyzed by Logistic regression.

Results:

Of the 34 patients in the infection group, 13 cases were cured, 21 cases improved, whereas in the control group, 15 cases were cured and 45 cases improved. There was no significant difference in prognosis between the 2 groups (P > 0.05). Univariate analysis showed that surgical approach, surgical duration, postoperative cerebrospinal fluid leakage, and external drainage were important factors for intracranial infection after craniotomy (P < 0.05). Further Logistic regression analysis showed that postoperative external drainage, cerebrospinal fluid leakage, surgical time, and posterior fossa approaches were independent risk factors for intracranial infection after craniotomy.

Conclusion:

High attention should be paid to the risk factors of intracranial infection after craniotomy such as postoperative cerebrospinal fluid leakage, external drainage, surgical duration and approach, and taking effective preventive measures to reduce the incidence of intracranial infection after craniotomy in patients with multiple traumatic injuries.
The Development of a New Medical Instrument: Modified Tongue Depressor
Authors: Sahin Caner , Doğan Bora
Published: September 2019

In the oropharyngeal region examinations, the abeslang (tongue depressor) used to create a wider field of vision and press down the tongue to make the pharynx easier. In order to look under the tongue, the depressor is redesigned so that it can be examined under the tongue and transformed into a retractor by creating an angle in the body of the present invention. This technique is intended to be used in conjunction with new technology surgical procedures. Our invention consists of the stem (1), the body (2), the end (3) and the notch (4), and the angle (5) in the angled model. This model, which is more effective than the routine tongue depressors at the same time it will not make any difference regarding cost. It will also allow the use of new surgical techniques while at the same time ensuring the exclusion of language in operations.
Surgical Treatment for Facial Port Wine Stain by Prefabricated Expanded Cervical Flap Carried by Superficial Temporal Artery
Authors: Chen Sen , Li Yangqun , Yang Zhe , Ma Ning , Wang Weixin , Xu Lisi , Liu Qiyu
Published: September 2019

Background:

Port wine stain (PWS) is a congenital benign vascular malformation. Laser treatment is the main therapy for PWS. But some patients are not sensitive to it, and failed laser treatment will leave scars on face. Hence in this study, the authors used prefabricated flap carried by superficial temporal artery to treat PWS.

Methods:

Nine patients diagnosed with large-scaled PWS (occupying more than half of the cheek) from January 2008 to December 2017 were selected in the study. One of them did not finish the treatment. Eight patients completed all scheduled treatments. In the first stage, superficial temporal vessels were transferred to the donor site and then an expander was implanted. About 80 to 150 days later, PWS was removed and the prefabricated flap was used to repair the wound. All the 8 patients were followed-up for 10 months to 36 months.

Results:

Prefabricated flap survived well. All patients are satisfied with the appearance. The color and texture of prefabricated flap is similar to the surroundings.

Conclusion:

The combination of prefabricated flap and skin soft tissue expander not only extends the scale of flap but also enhances the efficacy of surgical treatment. It is a good candidate to treat PWS.
Novel Technique and Step-by-Step Construction of a Computer-Guided Stent for Mandibular Distraction Osteogenesis
Authors: Hany Hossam El-Dien , El Hadidi Yasser Nabil , Sleem Heba , Taha Moustafa , El Kassaby Marwa
Published: September 2019

Introduction:

Distraction osteogenesis is an integral part in management of mandibular defects associated with hemifacial microsomia and post-ankylotic mandibular defects. The most difficult part in distraction osteogenesis is the prediction of distraction vector and risk of injury to vital structures as inferior alveolar. The present study aimed to present 3-dimensionally constructed computer-guided splints in distraction osteogenesis to get an ideal vector and minimal risk of vital structures injury.

Material and Methods:

The technical note presents cases series of 6 patients who had computer-guided distraction osteogenesis surgery using prefabricated splints.

Results:

The distance between the virtual and physical pins and osteotomy was measured, and the deviation of the vector angle and osteotomy angle was also assessed. Average deviation in pin distance was 3 mm and in vector angle 13.5°. Average deviation in osteotomy distance was 2.6 mm and in osteotomy angle 14.4°. None of the cases had injury to vital structure. There was significant improvement (P = 0.0078) in the medial canthus–buccal commissure distance where the arithmetic mean improved from 59.6 (SD = 10.1) mm pre-distraction in the defective side to 67.1 (SD = 8) mm post-distraction. The degree of correction was 97% compared to the normal side.

Conclusion:

3D printed surgical stents were successful in transferring the virtual treatment plan of mandibular distraction osteogenesis into the surgical theatre with an acceptable margin of error and without injury to any vital structures
Subperiosteal Dissection in Orbital Blowout Fracture: Technical Tips Including the Use of Modified Periosteal Elevator
Authors: Nazimi Abd. Jabar , Rajaran Jothi Raamahlingam , Nordin Rifqah
Published: September 2019

Orbital blowout fractures are common. The same goes for its surgical complications when the efficiency of the dissection of entrapped or herniated intraorbital contents into the fracture could not be completely and safely dissected out. The authors describe a modification of the commonly used Howarth periosteal elevator for dissection of intraorbital content displacement or herniation on orbital blowout fracture. The instrument was modified by marking out the instrument from the tip into 10, 20, 25, 30, and 40 mm on both of its concave and convex surfaces to allow safe orbital soft tissue dissection and distance control. From the authors’ experience, these simple modifications from its original instrument design allow better intraoperative control and appreciation of any intact important intraorbital anatomical structures such as inferomedial strut and posterior ledge. At the same time of importantly getting complete orbital fracture dissection and visualization, it causes less trauma to surrounding soft tissue with the markings ensuring unnecessary orbital exploration or visualization. Dissection can be kept for optimum maneuverability at the required or intended location based on the preoperative scan or dimension of anatomical orbital implant.
Does the Lag Time Between Injury and Treatment Play a Role in Recovery of Inferior Alveolar Nerve Neurosensory Disturbances Following Mandibular Body Fracture?
Authors: Tabrizi Reza , Pourdanesh Freydoun , Khoshnik Paniz Lesan , Centenero Samir Aboul-Hosn
Published: September 2019

Background:

The lag time between injury and treatment (LTIT) plays an important role in reduction of complications in mandibular fractures. The aim of this study was to measure the effect of LTIT on recovery of the inferior alveolar nerve (IAN) neurosensory disturbances (NSDs) following surgical management of mandibular body fractures.

Methods:

This was a prospective cohort study. Patients who had a unilateral mandibular body fracture with paresthesia were studied. Paresthesia was evaluated by 2-point discrimination (TPD) test, brush stroke test and self-reporting before and 6 months after the surgical procedure.

Results:

Forty-five patients were studied. There was a correlation between LTIT and TPD test result and self-reported paresthesia at 6 months, postoperatively (P = 0.001). Fifteen patients (33.3%) had complete improvement in NSD 6 months after treatments (group 1) and 30 patients (group 2) had hyposthesia (N = 17, 37.77%) and paresthesia (N = 13, 28.88%). There was a significant difference in LTIT between groups 1 and 2 at 6 months postoperatively (P = 0.001). Cox regression model demonstrated the hazard ratio increased significantly for self-reported NSD when treatment was done 10 days after trauma (P = 0.001, confidence level = 95%).

Conclusion:

It seems that conduction of open reduction with internal rigid fixation shortly after mandibular fracture may shorten the recovery time of NSDs of the IAN following mandibular body fractures.
Diagnosis of Bilateral Calcifications of Temporomandibular Joint Disc by Image Fusion
Authors: Han Wei-Hua , Meng Juan-Hong , Li Gang , Ma Xu-Chen
Published: September 2019

The calcification of the articular disc is an uncommon lesion, usually discovered in hips, elbows, and shoulders, but rarely in temporomandibular joints (TMJ). The TMJ disc calcification may be related to pain and limitation of the mandibular mobility, however, most of the patients were asymptomatic. A 61-year-old female was referred to our hospital after a maxillofacial fist injury, bilateral TMJ disc calcifications were found accidentally by radiological examination. Here the significance of image fusion of cone-beam computed tomography and magnetic resonance imaging (MRI) in the diagnosis of this lesion was emphasized.
The Gladiator's Tears: Epiphora From Ancient Rome
Authors: Galassi Francesco M. , Habicht Michael E. , Killgrove Kristina , De Carolis Stefano , Polidoro Massimo , Haeusler Martin
Published: September 2019

This article examines the clinical presentation of epiphora in Ancient Rome through the historico-medical analysis of the literary evidence provided by the verses by the poet Juvenal in his Satire VI. A gladiator's ophthalmological problem is interpreted as epiphora caused by traumatic injuries to the craniofacial region, compatible with those described in the palaeopathological literature. This analysis also focuses on the history of epiphora in antiquity and its treatment.
Three-Dimensional Analysis of Cortical Bone Thickness in Individuals With Non-Syndromic Unilateral Cleft Lip and Palate
Authors: Ko Jaemin , Han Hae Jin , Hoffman William , Oberoi Snehlata
Published: September 2019

Purpose:

The aim of this study was to measure the cortical bone thickness of the infrazygomatic crest area in individuals with unilateral cleft lip and palate using cone beam computed tomography for placement of miniplates used for bone anchored maxillary protraction.

Materials and Methods:

CBCT scans were obtained from 31 non-syndromic UCLP children diagnosed with maxillary hypoplasia (17 males, 14 females, mean age: 11.9 years). 5 horizontal and 5 vertical reference planes were drawn at the infrazygomatic crest area. The cortical bone thickness at 25 intersection points on the cleft side and the non-cleft side was measured.

Results:

The mean cortical bone thickness of the 25 measured points was 1.19 mm on the cleft side and 1.17 mm on the non-cleft side with no significant difference. The greatest cortical bone thickness was found to be at the most superior, posterior point (H+6, V+0), which was 1.49 mm on the cleft side and 1.47 mm on the non-cleft side. The thinnest mean cortical bone thickness was measured at the most inferior, anterior point (H−2, V−8), which was 0.94 mm on the cleft side and 0.95 mm on the non-cleft side. There was no significant difference between males and females.
Experience of Replantation and Reconstruction in Total Scalp, Partial Forehead, and Ear Avulsions
Authors: Dadaci Mehmet , Yildirim Mehmet Emin Cem , Ince Bilsev
Published: September 2019

In this study, the authors present the challenges of replantation and management of 2 patients who have total scalp, partial forehead and ear avulsion. A 39-year-old male farmer was admitted to the emergency room with the total scalp, forehead, partial right eyebrow and upper eyelid amputation after his hair was catched by an agricultural machine. Anastomoses of 2 arteries and 2 veins in the occipital region were done first. Anastomosis of the right and left superficial temporal arteries and veins were performed end to end by turning the operating table without moving the head, followed by 1 vein anastomoses in the frontal region. Although anastomotic blood flow was observed by Doppler ultrasonography, there were changes suggesting necrosis in the frontal and both temporoparietal regions and later in the occipital region. Necrotic tissues began to be debrided tangentially from the 10th day. During serial debridement, it was observed that the necrotic tissue includes skin and connective tissue. At the end of the post-operative second month, surgical treatment was completed and 12 months after the surgery, the patient lives with the wig because of hair loss, but the patient is cosmetically satisfied. An 18-year-old female gatherer was admitted to the emergency room with the total scalp, both eyebrows, right upper eyelid and partial right ear avulsion, after her hair was catched by an agricultural machine. Totally, anastomoses of 4 arteries and 3 veins were performed. On the 10th post-operative day, necrotic skin findings appeared and serial debridement were performed and it was revealed that aponeurosis was fully intact. The defect areas of skin and connective tissue were repaired with STSG. Intact partial temporal scalp tissue was present. Scalp replantation should always be considered as the first choice, according to the similar tissue principle of tissue repair in plastic surgery if there is no contraindication. Additionally, performing multiple arterial and vein anastomoses, evaluating the patient position in the post-operative period for anastomosis and hemodynamic follow-up, avoiding aggressive debridement and early reconstruction may give the patient the chance of skin grafting which is the basis of the reconstructive ladder.
Rise and Regional Disparities in Buprenorphine Utilization in the United States
Authors: Pashmineh Amir Azar R. , Cruz-Mullane Alexandra , Podd Jaclyn C. , Lam Warren S. , Kaleem Suhail H. , Lockard Laura B. , Mandel Mark R. , Chung Daniel Y. , Davis Corey S. , Nichols Stephanie D. , McCall Kenneth L. , Piper Brian J.
Published: September 2019

Aims

Buprenorphine is an opioid partial-agonist used to treat Opioid Use Disorders (OUD). While several state and federal policy changes have attempted to increase buprenorphine availability, access remains well below optimal levels. This study characterized how buprenorphine utilization in the United States has changed over time and whether there are regional disparities in distribution.

Measurements

Buprenorphine weights distributed from 2007 to 2017 were obtained from the Drug Enforcement Administration. Data was expressed as the percent change and as the mg per person in each state. Separately, the formulations for prescriptions covered by Medicaid (2008 to 2018) were examined.

Findings

Buprenorphine distributed to pharmacies increased about seven-fold (476.8 to 3,179.9 kg) while the quantities distributed to hospitals grew five-fold (18.6 to 97.6 kg) nationally from 2007 to 2017. Buprenorphine distribution per person was almost 20-fold higher in Vermont (40.4 mg/person) relative to South Dakota (2.1 mg/person). There was a strong association between the number of waivered physicians per 100K population and distribution per state (r(49) = +0.76, p < .0005). The buprenorphine/naloxone sublingual film (Suboxone) was the predominant formulation (92.6% of 0.31 million Medicaid prescriptions) in 2008 but this accounted for less than three-fifths (57.3% of 6.56 million prescriptions) in 2018.

Conclusions

Although buprenorphine availability has substantially increased over the last decade, distribution was very non-homogenous across the US.
Electrophysiological network alterations in adults with copy number variants associated with high neurodevelopmental risk
Authors: Dima Diana C. , Adams Rachael , Linden Stefanie C. , Baird Alister , Smith Jacqueline , Foley Sonya , Perry Gavin , Routley Bethany C. , Magazzini Lorenzo , Drakesmith Mark , Williams Nigel , Doherty Joanne , van den Bree Marianne B.M. , Owen Michael J. , Hall Jeremy , Linden David E. J. , Singh Krish D.
Published: September 2019

Rare copy number variants associated with increased risk for neurodevelopmental and psychiatric disorders (referred to as ND-CNVs) are characterized by heterogeneous phenotypes thought to share a considerable degree of overlap. Altered neural integration has often been linked to psychopathology and is a candidate marker for potential convergent mechanisms through which ND-CNVs modify risk; however, the rarity of ND-CNVs means that few studies have assessed their neural correlates. Here, we used magnetoencephalography (MEG) to investigate resting-state oscillatory connectivity in a cohort of 42 adults with ND-CNVs, including deletions or duplications at 22q11.2, 15q11.2, 15q13.3, 16p11.2, 17q12, 1q21.1, 3q29, and 2p16.3, and 42 controls. We observed decreased connectivity between occipital, temporal and parietal areas in participants with ND-CNVs. This pattern was common across genotypes and not exclusively characteristic of 22q11.2 deletions, which were present in a third of our cohort. Furthermore, a data-driven graph theory framework enabled us to successfully distinguish participants with ND-CNVs from unaffected controls using differences in node centrality and network segregation. Together, our results point to alterations in electrophysiological connectivity as a putative common mechanism through which genetic factors confer increased risk for neurodevelopmental and psychiatric disorders.
OmicsX: a web server for integrated OMICS analysis
Authors: Pan Jianbo , Qian Jiang , Zhang Hui
Published: September 2019

High-throughput omic data sets like genomics, transcriptomics, proteomics, glycomics, lipitomics, metabolomics, and modified forms of the biological molecules have been generated to investigate biological mechanisms. Accordingly, bioinformatic methods and tools have been developed and applied to analyze the omics data for different purposes. However, a lack of comparison and integration tools impedes the deep exploration of multi-omics data. OmicsX is a user-friendly web server for integration and comparison of different omic datasets with optional sample annotation information. The tool includes modules for gene-wise correlation, sample-wise correlation, subtype clustering, and differential expression. OmicsX provides researchers the analysis results with visualization, searching, and data downloading, and help to suggest the biological indications from the comparison of different omic data.

Availability and implementation

http://bioinfo.wilmer.jhu.edu/OmicsX/
The scale-invariant, temporal profile of neuronal avalanches in relation to cortical γ–oscillations
Authors: Miller Stephanie R. , Yu Shan , Plenz Dietmar
Published: September 2019

Activity cascades are found in many complex systems. In the cortex, they arise in the form of neuronal avalanches that capture ongoing and evoked neuronal activities at many spatial and temporal scales. The scale-invariant nature of avalanches suggests that the brain is in a critical state, yet predictions from critical theory on the temporal unfolding of avalanches have yet to be confirmed in vivo. Here we show in awake nonhuman primates that the temporal profile of avalanches follows a symmetrical, inverted parabola spanning up to hundreds of milliseconds. This parabola constrains how avalanches initiate locally, extend spatially and shrink as they evolve in time. Importantly, parabolas of different durations can be collapsed with a scaling exponent close to 2 supporting critical generational models of neuronal avalanches. Spontaneously emerging, transient γ–oscillations coexist with and modulate these avalanche parabolas thereby providing a temporal segmentation to inherently scale-invariant, critical dynamics. Our results identify avalanches and oscillations as dual principles in the temporal organization of brain activity.

Significance Statement

The most common framework for understanding the temporal organization of brain activity is that of oscillations, or ‘brain waves’. In oscillations, distinct physiological frequencies emerge at well-defined temporal scales, dividing brain activity into time segments underlying cortex function. Here, we identify a fundamentally different temporal parsing of activity in cortex. In awake Macaque monkeys, we demonstrate the motif of an inverted parabola that governs the temporal unfolding of brain activity in the form of neuronal avalanches. This symmetrical motif is scale-invariant, that is, it is not tied to time segments, and exhibits a scaling exponent close to 2, in line with prediction from theory of critical systems. We suggest that oscillations provide a transient regularity in an otherwise scale-invariant temporal organization pervading cortical activity at numerous scales.
An improved Xer-cise technology for the generation of multiple unmarked mutants in Mycobacteria
Authors: Boudehen Yves-Marie , Wallat Maximillian , Rousseau Philippe , Neyrolles Olivier , Gutierrez Claude
Published: September 2019

Xer-cise is a technique using antibiotic resistance cassettes flanked by dif sites allowing spontaneous and accurate excision from bacterial chromosomes with a high frequency through the action of the cellular recombinase XerCD. Here, we report a significant improvement of Xer-cise in Mycobacteria. Zeocin-resistance cassettes flanked by variants of the natural Mycobacterium tuberculosis dif site were constructed and shown to be effective tools to construct multiple unmarked mutations in M. tuberculosis and in the model species Mycobacterium smegmatis. The dif site variants harbor mutations in the central region and can therefore not recombine with the wild type or other variants, resulting in mutants of increased genetic stability. The herein described method should be generalizable to virtually any transformable bacterial species.

Method summary

dif-ZeoR-dif cassettes are used to replace non-essential genes in mycobacterial genome through recombineering. Spontaneous excision of the cassette is carried out under the action of the recombinase XerCD, resulting in unmarked deletions. Subsequent rounds of mutagenesis using cassettes flanked by a range of dif site variants allow construction of multiple mutants in which the different dif sites cannot recombine which each other, yielding stable genetic constructs.
ADNP promotes neural differentiation by modulating Wnt/β-catenin signaling
Authors: Sun Xiaoyun , Peng Xixia , Cao Yuqing , Zhou Yan , Sun Yuhua
Published: September 2019

ADNP (Activity Dependent Neuroprotective Protein) is proposed as a neuroprotective protein whose aberrant expression has been frequently linked to neural developmental disorders, including the Helsmoortel-Van der Aa syndrome. However, its role in neural development and pathology remains unclear. Using mESC (mouse embryonic stem cell) directional neural differentiation as a model, we show that ADNP is required for ESC neural induction and neuronal differentiation by maintaining Wnt signaling. Mechanistically, ADNP functions to maintain the proper protein levels of β-Catenin through binding to its armadillo domain which prevents its association with key components of the degradation complex: Axin and APC. Loss of ADNP promotes the formation of the degradation complex and hyperphosphorylation of β-Catenin by GSK3β and subsequent degradation via ubiquitin-proteasome pathway, resulting in down-regulation of key neuroectoderm developmental genes. We further show that ADNP plays key role in cerebellar neuron formation. Finally, adnp gene disruption in zebrafish embryos recapitulates key features of the mouse phenotype, including the reduced Wnt signaling, defective embryonic cerebral neuron formation and the massive neuron death. Thus, our work provides important insights into the role of ADNP in neural development and the pathology of the Helsmoortel-Van der Aa syndrome caused by ADNP gene mutation.
AFM based elasticity of intestinal epithelium correlate with barrier function under drug action
Authors: Tejeda-Mora H. , Stevens L. , Gröllers M. , Katan A. , van de Steeg E. , van der Heiden M.
Published: September 2019

Over the past few years, atomic force microscopy (AFM) has developed as a mature research tool for measuring the nanomechanical properties of tissue, cells and biological structures. The force spectroscopy mode of AFM allows the local elasticity of biological samples to be measured. The mechanical properties of cells are highly affected by homeostatic changes observed during disease. In the case of the intestine, the aetiology for some conditions is still unclear. To improve the clinical translation of pre-clinical models, a new and different approach could be to study cellular behaviour in health and disease from a mechanical point of view. Specifically, knowledge of changes in epithelial membranes in response to drugs is useful for interpreting both drug action and disease development. Here, we used human intestinal Caco-2 cells as a first step to record epithelial membrane elasticity measurements at the nanoscale using AFM. Three different drugs were selected to influence intestinal epithelium integrity by specifically targeting different functional aspects of the membrane, such as permeability and support. Results indicate a relationship between measured cell elasticity and cell viability markers, such as cellular toxicity and membrane barrier functions. Our work represents a proof-of-concept that cells suffer a particular change in elastic properties depending upon the mechanism of action of an applied drug. The following may provide an efficient approach for diagnosing intestinal pathologies and testing drugs for clinical use.

STATEMENT OF SIGNIFICANCE

We present evidence that epithelial membrane suffers a particular change in elastic properties depending upon the mechanism of action of an applied drug. These changes can be monitored over time using AFM technology and may provide an alternative and efficient approach for diagnosing intestinal pathologies and testing drugs for clinical use.
Ultra-Conserved Elements and morphology reciprocally illuminate conflicting phylogenetic hypotheses in Chalcididae (Hymenoptera, Chalcidoidea)
Authors: Cruaud Astrid , Delvare Gérard , Nidelet Sabine , Sauné Laure , Ratnasingham Sujeevan , Chartois Marguerite , Blaimer Bonnie B. , Gates Michael , Brady Seán G. , Faure Sariana , van Noort Simon , Rossi Jean-Pierre , Rasplus Jean-Yves
Published: September 2019

Recent technical advances combined with novel computational approaches promised the acceleration of our understanding of the tree of life. However, when it comes to hyperdiverse and poorly known groups of invertebrates, studies are still scarce. As published phylogenies will be rarely challenged by future taxonomists, careful attention must be paid to potential analytical bias. We present the first molecular phylogenetic hypothesis for the family Chalcididae, an emblematic group of parasitoid wasps, with a representative sampling (144 ingroups and 7 outgroups) that covers all described subfamilies and tribes and 82% of the known genera. Analyses of 538 Ultra-Conserved Elements (UCEs) with supermatrix (RAxML and IQTREE) and gene-tree reconciliation approaches (ASTRAL, ASTRID) resulted in highly supported topologies in overall agreement with morphology but reveal conflicting topologies for some of the deepest nodes. To resolve these conflicts, we explored the phylogenetic tree space with clustering and gene genealogy interrogation methods, analyzed marker and taxon properties that could bias inferences and performed a thorough morphological analysis (130 characters encoded for 40 taxa representative of the diversity). This joint analysis reveals that UCEs enable attainment of resolution between ancestry and convergent /divergent evolution when morphology is not informative enough, but also shows that a systematic exploration of bias with different analytical methods and a careful analysis of morphological features is required to prevent publication of artefactual results. We highlight a GC-content bias for ML approaches, an artefactual mid-point rooting of the ASTRAL tree and a deleterious effect of high percentage of missing data on gene tree reconciliation methods. Based on the results we propose a new classification of the family into eight subfamilies and 10 tribes that lay the foundation for future studies on the evolutionary history of Chalcididae.
Designing of a mini-core that effectively represents 3004 diverse accessions of rice
Authors: Kumar Angad , Kumar Shivendra , Prasad Manoj , Thakur Jitendra K.
Published: September 2019

Genetic diversity provides foundation for plant breeding and genetic research. As part of the 3K Rice Genome Project, over 3000 rice genomes were recently sequenced. We added four Indian rice accessions to it and made original panel of 3004 accessions. However, large set of germplasms are difficult to preserve and evaluate. Construction of core and mini-core collections is an efficient method for managing genetic resources. This study aims to designing of mini-core comprised of 520 accessions representing original panel. The designed mini-core captured most of the SNPs and represented all phenotypes and geographical regions. The mini-core was validated using different statistical analyses and had representation from all major groups including japonica, indica, aus/boro and aromatic/basmati. GWAS analyses with mini-core panel efficiently reproduced the marker-traits association identified among original 3004 panel. Expression analysis of trait-associated genes highlights the relevance of such mini-core panel. Haplotype analysis could also validate our mini-core panel. Apart from mini-core, we identified few regional and varietal specific marker-trait associations which were not evident in original panel. In this era of large-scale sequencing projects, such a strategy of designing mini-core will be very useful.

One-sentence summary

Designing of mini-core as manageable association panel that efficiently mirroring the large and diverse collection of 3004 rice accessions.
Physical activity and risks of breast and colorectal cancer: A Mendelian randomization analysis
Authors: Papadimitriou Nikos , Dimou Niki , Tsilidis Konstantinos K , Banbury Barbara , Martin Richard M , Lewis Sarah J , Kazmi Nabila , Robinson Timothy M , Albanes Demetrius , Aleksandrova Krasimira , Berndt Sonja I , Bishop D Timothy , Brenner Hermann , Buchanan Daniel D , Bueno-de-Mesquita Bas , Campbell Peter T , Castellví-Bel Sergi , Chan Andrew T , Chang-Claude Jenny , Ellingjord-Dale Merete , Figueiredo Jane C , Gallinger Steven J , Giles Graham G , Giovannucci Edward , Gruber Stephen B , Gsur Andrea , Hampe Jochen , Hampel Heather , Harlid Sophia , Harrison Tabitha A , Hoffmeister Michael , Hopper John L , Hsu Li , Huerta José María , Huyghe Jeroen R , Jenkins Mark A , Keku Temitope O , Kühn Tilman , Vecchia Carlo La , Marchand Loic Le , Li Christopher I , Li Li , Lindblom Annika , Lindor Noralane M , Lynch Brigid , Markowitz Sanford D , Masala Giovanna , May Anne M , Milne Roger , Monninkhof Evelyn , Moreno Lorena , Moreno Victor , Newcomb Polly A , Offit Kenneth , Perduca Vittorio , Pharoah Paul D P , Platz Elizabeth A , Potter John D , Rennert Gad , Riboli Elio , Sánchez Maria-Jose , Schmit Stephanie L , Schoen Robert E , Severi Gianluca , Sieri Sabina , Slattery Martha L , Song Mingyang , Tangen Catherine M , Thibodeau Stephen N , Travis Ruth C , Trichopoulou Antonia , Ulrich Cornelia M , van Duijnhoven Franzel JB , Van Guelpen Bethany , Vodicka Pavel , White Emily , Wolk Alicja , Woods Michael O , Wu Anna H , Peters Ulrike , Gunter Marc J , Murphy Neil
Published: September 2019

Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomization analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.59, 95% confidence interval [CI]: 0.42 to 0.84, P-value=0.003) and colorectal cancer (OR: 0.66, 95% CI: 0.53 to 0.82, P-value=2*E-4). We found similar magnitude inverse associations by breast cancer subtype and by colorectal cancer anatomical site. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.

Disclaimer

Where authors are identified as personnel of the International Agency for Research on Cancer / World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.
Genome reconfiguration prior to mitosis shapes the generation of adaptive immunity
Authors: Chan Wing Fuk , Coughlan Hannah D. , Zhou Jie H.S. , Keenan Christine R. , Bediaga Naiara G. , Hodgkin Phillip D. , Smyth Gordon K. , Johanson Timothy M. , Allan Rhys S.
Published: September 2019

During cellular differentiation chromosome conformation is altered to support the lineage-specific transcriptional programs required for cell identity. When these changes occur in relation to cell cycle, division and time is unclear. Here we followed B lymphocytes as they differentiated from a naïve, quiescent state into antibody secreting plasma cells. Unexpectedly, we found that gene-regulatory chromosome reorganization occurred prior to the first division, in late G1 phase and that this configuration is maintained as the cells rapidly cycle during clonal expansion. A second wave of architectural changes also occurred later as cells differentiated into plasma cells and this was associated with increased time in G1 phase. These data provide an explanation for how lymphocyte fate is imprinted prior to the first division and suggest that chromosome reconfiguration is spatiotemporally separated from DNA replication and mitosis to ensure the implementation of a gene regulatory program that controls the differentiation process required for the generation of immunity.

One Sentence Summary

Discrete waves of genome reorganization, spatiotemporally separated from DNA replication and mitosis, control cell differentiation.
Does higher sampling rate (Multiband + SENSE) benefit the detection of task correlated BOLD for cognitive neuroscience applications at 3T?
Authors: Bhandari Ritu , Kirilina Evgeniya , Caan Matthan , Suttrup Judith , de Sanctis Teresa , De Angelis Lorenzo , Keysers Christian , Gazzola Valeria
Published: September 2019

Multiband (MB) or Simultaneous multi-slice (SMS) acquisition schemes allow the acquisition of MRI signals from more than one spatial coordinate at a time. Commercial availability has brought this technique within the reach of many neuroscientists and psychologists. Most early evaluation of the performance of MB acquisition employed resting state fMRI or the most basic tasks. In this study, we tested whether the advantages of using MB acquisition schemes generalize to group analyses using a cognitive task more representative of typical cognitive neuroscience applications. Twenty-three subjects were scanned on a Philips 3T scanner using five sequences up to eight-fold acceleration with MB-factors 1 to 4, SENSE factors up to 2 and corresponding TRs of 2.45s down to 0.63s, while they viewed (i) movies showing complex actions with hand object interactions and (ii) control movies without hand object interaction. Using random effects group-level, voxel-wise analysis we found that all sequences were able to detect the basic action observation network known to be recruited by our task. The highest t-values were found for sequences with MB4 acceleration. For the MB1 sequence, a 50% bigger voxel volume was needed to reach comparable t-statistics. The group-level t-values for resting state networks (RSNs) were also highest for MB4 sequences. Here the MB1 sequence with larger voxel size did not perform comparable to the MB4 sequence. Altogether, we can thus recommend the use of MB4 (and SENSE 1.5 or 2) on a Philips scanner when aiming to perform group-level analyses using cognitive block design fMRI tasks and voxel sizes in the range of cortical thickness (e.g. 2.7mm isotropic). While results will not be dramatically changed by the use of multiband, our results suggest that MB will bring a moderate but significant benefit.
Structural Diversity of B-Cell Receptor Repertoires along the B-cell Differentiation Axis in Humans and Mice
Authors: Kovaltsuk Aleksandr , Raybould Matthew I. J. , Wong Wing Ki , Marks Claire , Kelm Sebastian , Snowden James , Trück Johannes , Deane Charlotte M.
Published: September 2019

Most current analysis tools for antibody next-generation sequencing data work with primary sequence descriptors, leaving accompanying structural information unharnessed. We have used novel rapid methods to structurally characterize the paratopes of more than 180 million human and mouse B-cell receptor (BCR) repertoire sequences. These structurally annotated paratopes provide unprecedented insights into both the structural predetermination and dynamics of the adaptive immune response. We show that B-cell types can be distinguished based solely on these structural properties. Antigen-unexperienced BCR repertoires use the highest number and diversity of paratope structures and these patterns of naïve repertoire paratope usage are highly conserved across subjects. In contrast, more differentiated B-cells are more personalized in terms of paratope structure usage. Our results establish the paratope structure differences in BCR repertoires and have applications for many fields including immunodiagnostics, phage display library generation, and “humanness” assessment of BCR repertoires from transgenic animals.