bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA MCF2L-AS1 aggravates proliferation, invasion and glycolysis of colorectal cancer cells via the crosstalk with miR-874-3p/FOXM1 signaling axis
Authors: Zhang Zhandong , Yang Wei , Li Ning , Chen Xiaobin , Ma Fei , Yang Jian , Zhang Yonglei , Chai XiaoFei , Zhang Bin , Hou Xinfang , Luo Suxia , Hua Yawei
Published: August 2020

Long non-coding RNAs (lncRNAs) regulate a series of biological processes, and their anomalous expression exerts critical roles in progression of multiple malignancies, including colorectal cancer (CRC). The present study was designed to provide new ideas and perspectives for the role of lncRNA MCF2L-AS1 and disclose the underlying mechanism in CRC. Herein, we observed that MCF2L-AS1 expression was enriched in CRC tissues and cell lines. Additionally, silencing of MCF2L-AS1 dramatically impeded cell proliferation, invasion and migration capacities of CRC, and distinctly attenuated the expression of invasion associated targets MMP-2 and MMP-9. Moreover, depletion of MCF2L-AS1 apparently restricted the glucose consumption and lactate production, and downregulated GLUT1 and LDHA expression. More importantly, we predicted and verified that MCF2L-AS1 acted as a molecular sponge for miR-874-3p and inversely regulated miR-874-3p expression. Interesting, FOXM1 was identified as direct target of miR-874-3p, and positively modulated by MCF2L-AS1 through sponging miR-874-3p. Mechanistically, MCF2L-AS1 accelerated cell proliferation, invasion and glycolysis through competitively binding to miR-874-3p, leading to enhance FOXM1 expression. Collectively, these outcomes highlighted that MCF2L-AS1 acted as a motivator by modulating the miR-874-3p/FOXM1 axis, thereby aggravating tumorigenesis and glycolysis progress of CRC, disclosing that MCF2L-AS1 may serve as a valuable and promising therapeutic strategy for CRC.
Rates of New Human Papillomavirus Detection and Loss of Detection in Middle-aged Women by Recent and Past Sexual Behavior
Authors: Paul Proma , Hammer Anne , Rositch Anne F , Burke Anne E , Viscidi Raphael P , Silver Michelle I , Campos Nicole , Youk Ada O , Gravitt Patti E
Published: August 2020

Background

Understanding the source of newly detected human papillomavirus (HPV) in middle-aged women is important to inform preventive strategies, such as screening and HPV vaccination.

Methods

We conducted a prospective cohort study in Baltimore, Maryland. Women aged 35–60 years underwent HPV testing and completed health and sexual behavior questionnaires every 6 months over a 2-year period. New detection/loss of detection rates were calculated and adjusted hazard ratios were used to identify risk factors for new detection.

Results

The new and loss of detection analyses included 731 women, and 104 positive for high-risk HPV. The rate of new high-risk HPV detection was 5.0 per 1000 woman-months. Reporting a new sex partner was associated with higher detection rates (adjusted hazard ratio, 8.1; 95% confidence interval, 3.5–18.6), but accounted only for 19.4% of all new detections. Among monogamous and sexually abstinent women, new detection was higher in women reporting ≥5 lifetime sexual partners than in those reporting <5 (adjusted hazard ratio, 2.2; 95% confidence interval, 1.2–4.2).

Conclusion

Although women remain at risk of HPV acquisition from new sex partners as they age, our results suggest that most new detections in middle-aged women reflect recurrence of previously acquired HPV.
Suppurative Intracranial Complications of Pediatric Sinusitis: A Single-Center Experience
Authors: Otto William R , Paden William Z , Connors Meghan , Joerger Torsten , Buzi Adva , Rizzi Mark , Huh Jimmy , Storm Phillip , Heuer Gregory , Kennedy Benjamin , McGuire Jennifer , Swami Sanjeev , Lang Shih-Shan
Published: August 2020

Background

Suppurative intracranial complications of sinusitis are rare events in children and can lead to harmful neurologic sequelae and significant morbidity. We sought to review the presentation and management of patients admitted at our hospital with these conditions.

Methods

This was a retrospective study of pediatric patients admitted to a quaternary children’s hospital from 2007 to 2019 for operative management of sinusitis with intracranial extension. Clinical characteristics, including surgical and microbiological data, were collected and analyzed.

Results

Fifty-four patients were included; the median age was 11.0 years, and there was a male predominance. Eighty-nine percent of patients had prior healthcare visits for the current episode of sinusitis; 46% of patients had an abnormal neurologic exam on admission. Epidural abscess and subdural empyema were the most common complications, and subdural empyema was associated with repeat surgical intervention. The dominant pathogens were Streptococcus anginosus group organisms (74%). The majority of patients completed treatment parenterally, with a median duration of therapy of 35 days. Neurological sequelae, including epilepsy or ongoing focal deficits, occurred in 22% of patients. History of seizure or an abnormal neurological exam at admission were associated with neurological sequelae.

Conclusions

Clinicians should consider intracranial complications of sinusitis in patients with symptoms of sinusitis for >1 week. Patients should undergo urgent neuroimaging, as neurosurgical intervention is essential for these patients. Subdural empyema was associated with repeat neurosurgical intervention. Neurological sequelae occurred in 22% of patients, and new onset seizure or an abnormal neurological exam at admission were associated with neurological sequelae.
Calibration of Chronic Lung Disease Severity as a Risk Factor for Respiratory Syncytial Virus Hospitalization
Authors: Choi Yoonyoung , Meissner H Cody , Hampp Christian , Park Haesuk , Brumback Babette , Winterstein Almut G
Published: August 2020

Background

Guidelines assume children with chronic lung disease (CLD) who require medical support within 6 months before the second respiratory syncytial virus (RSV) season remains at high risk of severe RSV disease. We determined the number of days since the last treatment (DSL) when the risk of RSV hospitalization among children with CLD becomes equivalent to the risk for those not qualified for immunoprophylaxis.

Methods

The study cohort was assembled using Medicaid billing records from 1999 to 2010 linked to Florida and Texas birth certificate records. We developed DSL-trend discrete time logistic regression models within a survival analysis framework, adjusting for use of immunoprophylaxis, to compare the hospitalization risk of CLD infants at 4 age points to that of term infants at 1 month of age with siblings.

Results

The study cohort included 858 830 healthy term and 5562 preterm infants with CLD. Among 1-month-old term infants, the RSV hospitalization risk averaged across all covariate strata was 14.8 (95% confidence interval [CI], 13.5–16.1) per 1000 patient season-months. Risk for preterm CLD children reached the threshold derived from term infants when DSL was 76 (95% CI, 22–198.5), 52 (95% CI, 6.5–123), 35 (95% CI, 0–93.5), and 12 (95% CI, 0–61.5) at the respective ages of 12, 15, 17.2, and 21 months.

Conclusions

The 180-day threshold used to define CLD severity at season start can be shortened to 120 days, 90 days, and 60 days for children with CLD at age 15, 17.2, and 21 months, respectively.
GAMA + KiDS: empirical correlations between halo mass and other galaxy properties near the knee of the stellar-to-halo mass relation
Authors: Taylor Edward N , Cluver Michelle E , Duffy Alan , Gurri Pol , Hoekstra Henk , Sonnenfeld Alessandro , Bremer Malcolm N , Brouwer Margot M , Chisari Nora Elisa , Dvornik Andrej , Erben Thomas , Hildebrandt Hendrik , Hopkins Andrew M , Kelvin Lee S , Phillipps Steven , Robotham Aaron S G , Sifón Cristobál , Vakili Mohammadjavad , Wright Angus H
Published: August 2020

We use KiDS weak lensing data to measure variations in mean halo mass as a function of several key galaxy properties (namely stellar colour, specific star formation rate, Sérsic index, and effective radius) for a volume-limited sample of GAMA galaxies in a narrow stellar mass range [M* ∼ (2–5) × 1010 M⊙]. This mass range is particularly interesting, inasmuch as it is where bimodalities in galaxy properties are most pronounced, and near to the break in both the galaxy stellar mass function and the stellar-to-halo mass relation (SHMR). In this narrow mass range, we find that both size and Sérsic index are better predictors of halo mass than either colour or SSFR, with the data showing a slight preference for Sérsic index. In other words, we find that mean halo mass is more tightly correlated with galaxy structure than either past star formation history or current star formation rate. Our results lead to an approximate lower bound on the dispersion in halo masses among log M* ≈ 10.5 galaxies: We find that the dispersion is ≳0.3 dex. This would imply either that offsets from the mean SHMR are closely coupled to size/structure or that the dispersion in the SHMR is larger than what past results have suggested. Our results thus provide new empirical constraints on the relationship between stellar and halo mass assembly at this particularly interesting mass range.
Integrated dynamic wet spinning of core-sheath hydrogel fibers for optical-to-brain/tissue communications
Authors: Chen Guoyin , Wang Gang , Tan Xinrong , Hou Kai , Meng Qingshuo , Zhao Peng , Wang Shun , Zhang Jiayi , Zhou Zhan , Chen Tao , Cheng Yanhua , Hsiao Benjamin S , Reichmanis Elsa , Zhu Meifang
Published: August 2020

Hydrogel optical light-guides have received substantial interest for applications such as deep-tissue biosensors, optogenetic stimulation and photomedicine due to their biocompatibility, (micro)structure control and tissue-like Young's modulus. However, despite recent developments, large-scale fabrication with a continuous synthetic methodology, which could produce core-sheath hydrogel fibers with the desired optical and mechanical properties suitable for deep-tissue applications, has yet to be achieved. In this study, we report a versatile concept of integrated light-triggered dynamic wet spinning capable of continuously producing core-sheath hydrogel optical fibers with tunable fiber diameters, and mechanical and optical propagation properties. Furthermore, this concept also exhibited versatility for various kinds of core-sheath functional fibers. The wet spinning synthetic procedure and fabrication process were optimized with the rational design of the core/sheath material interface compatibility [core = poly(ethylene glycol diacrylate-co-acrylamide); sheath = Ca-alginate], optical transparency, refractive index and spinning solution viscosity. The resulting hydrogel optical fibers exhibited desirable low optical attenuation (0.18 ± 0.01 dB cm−1 with 650 nm laser light), excellent biocompatibility and tissue-like Young's modulus (<2.60 MPa). The optical waveguide hydrogel fibers were successfully employed for deep-tissue cancer therapy and brain optogenetic stimulation, confirming that they could serve as an efficient versatile tool for diverse deep-tissue therapy and brain optogenetic applications.
Ryanodine Receptor Type 2: A Molecular Target for Dichlorodiphenyltrichloroethane- and Dichlorodiphenyldichloroethylene-Mediated Cardiotoxicity
Authors: Truong Kim M , Feng Wei , Pessah Isaac N
Published: August 2020

Dichlorodiphenyltrichloroethane (DDT) and its metabolite dichlorodiphenyl-dichloroethylene (DDE) are ubiquitously found in the environment and linked to cardiovascular diseases—with a majority of the work focused on hypertension. Studies investigating whether DDx can interact with molecular targets on cardiac tissue to directly affect cardiac function are lacking. Therefore, we investigated whether o,pʹ-DDT, p,pʹ-DDT, o,pʹ-DDE, or p,pʹ-DDE (DDx, collectively) can directly alter the function of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) by assessing their effect(s) on hiPSC-CMs Ca2+ dynamics. DDx (0.1–10 µM) affected hiPSC-CMs synchronous Ca2+ oscillation frequency in a concentration-dependent manner, with p,pʹ-DDT and p,pʹ-DDE also decreasing Ca2+ stores. HEK-RyR2 cells cultured under antibiotic selection to induce expression of wild-type mouse ryanodine receptor type 2 (RyR2) are used to further investigate whether DDx alters hiPSC-CMs Ca2+ dynamics through engagement with RyR2, a protein critical for cardiac muscle excitation-contraction coupling (ECC). Acute treatment with 10 µM DDx failed to induce Ca2+ release in HEK293-RyR2, whereas pretreatment with DDx (0.1–10 µM) for 12- or 24-h significantly decreased sarcoplasmic reticulum Ca2+ stores in HEK-RyR2 cells challenged with caffeine (1 mM), an RyR agonist. [3H]ryanodine-binding analysis using murine cardiac RyR2 homogenates further confirmed that all DDx isomers (10 µM) can directly engage with RyR2 to favor an open (leaky) confirmation, whereas only the DDT isomers (10 µM) modestly (≤10%) inhibited SERCA2a activity. The data demonstrate that DDx increases heart rate and depletes Ca2+ stores in human cardiomyocytes through a mechanism that impairs RyR2 function and Ca2+ dynamics.

Impact Statement

DDT/DDE interactions with RyR2 alter cardiomyocyte Ca2+ dynamics that may contribute to adverse cardiovascular outcomes associated with exposures.
Shilla Growth Guidance Compared With Magnetically Controlled Growing Rods in the Treatment of Neuromuscular and Syndromic Early-onset Scoliosis
Authors: Haapala Hermanni , Saarinen Antti J. , Salonen Anne , Helenius Ilkka
Published: August 2020

Study Design.

Retrospective review of consecutive series of patients treated at two institutions.

Objective.

The aim of this study was to compare the health-related quality of life (HRQoL) and surgical outcomes of Shilla growth guidance and magnetically controlled growing rod (MCGR) treatment in patients with syndromic and neuromuscular early-onset scoliosis (EOS).

Summary of Background Data.

Knowledge of the outcomes of Shilla instrumentation is limited.

Methods.

We identified 13 children treated with Shilla and 18 children treated with MCGR with syndromic or neuromuscular EOS (major curve ≥45 degree) before the age of 10 years with minimum 2-year follow-up. Outcome parameters included clinical data, radiographic as well as HRQoL outcomes (EOSQ-24 questionnaire).

Results.

Mean preoperative major curves were 64 degree (range, 45–108 degree) in the Shilla group and 58 degree (range, 45–85 degree) in the MCGR group (P = 0.151). At final follow-up, mean major curves were 31 degree (range, 9.4–54 degree ) and 30 degree (range, 16–53 degree), respectively (P = 0.392). The mean major curve correction was 45% in the Shilla group and 48% in the MCGR group during the follow-up (P = 0.383). Spinal (T1-S1) and T1-T12 growth were significantly better (P = 0.006 and 0.042) in the MCGR than in the Shilla group during the distraction period. At final follow-up, 11 (85%) children in the Shilla group and 17 (94%) in the MCGR group had achieved T1-T12 length of ≥18 cm (P = 0.202). There were significantly more surgical procedures in the MCGR group (mean 2.6 vs. 1.4, P = 0.034) with no difference in the number of complications (P = 0.768). EOSQ24 domains were similar at final follow-up.

Conclusion.

Shilla growth guidance provided similar correction of spinal deformity, equal number of complications, but with significantly less surgical procedures in patients treated for EOS when compared with MCGR instrumentation. MCGR provided with slightly better spinal growth during the distraction period. There were no significant differences between the quality of life assessments.

Level of Evidence: 3
Complete Tumor Regression by Liposomal Bortezomib in a Humanized Mouse Model of Multiple Myeloma
Authors: Deshantri Anil K. , Fens Marcel H.A.M. , Ruiter Ruud W.J. , Metselaar Josbert M. , Storm Gert , Mandhane Sanjay N. , Graat Gerard H.M. , Lentjes Eef G.W. , Yuan Huipin , de Bruijn Joost D. , Mutis Tuna , Martens Anton C.M. , Groen Richard W.J. , Schiffelers Raymond M.
Published: August 2020

Supplemental Digital Content is available in the text
Corneal Scheimpflug Densitometry in Photorefractive Keratectomy Candidates
Authors: Pakbin Mojgan , Khabazkhoob Mehdi , Pakravan Mohammad , Fotouhi Akbar , Jafarzadehpur Ebrahim , Aghamirsalim Mohamadreza , Hashemi Hassan
Published: August 2020

Purpose:

To describe the normative data of corneal densitometry in photorefractive Keratectomy (PRK) candidates by using a Scheimpflug camera.

Methods:

Five hundred twenty-two eyes of 261 PRK candidates that underwent comprehensive optometric and ophthalmic examinations were enrolled in this study. Corneal densitometry values were obtained using a Scheimpflug camera (Pentacam HR; Oculus Optikgeräte GmbH, Wetzlar, Germany) and displayed in grayscale units (GSU).

Results:

Of 261 participants, 187 (71.6%) were women. The mean age of the participants was 28.79 ± 5.02 years (range: 21–40 years). The mean entire corneal densitometry was 14.86 ± 2.37 GSU. According to corneal depth, maximum and minimum densitometry values were seen in the anterior (30.28 ± 7.42 GSU) and posterior (9.86 ± 2.08 GSU) layers, respectively (P < 0.001). Based on the annulus over the cornea, the highest and lowest densitometry values were seen in the 10- to 12-mm (21.31 ± 4.26 GSU) and 2- to 6-mm zones (13.26 ± 2.34 GSU), respectively. However, this difference was not seen after 35 years of age. Individuals aged 30 to 35 years showed higher corneal densitometry values compared with subjects aged 20 to 25 years old (P < 0.001). In generalized linear models, the corneal thickness was associated with the densitometry value in the central and posterior corneal layers. There were no significant differences in sex and refractive errors among participants.

Conclusions:

This study provided normal corneal densitometry data in PRK candidates. Corneal densitometry increased with age until 35 years of age and then decreased thereafter. This finding should be considered in patient selection for PRK and their postoperative examinations.
Concordance analysis of intrapartum cardiotocography between physicians and artificial intelligence-based technique using modified one-dimensional fully convolutional networks
Authors: Liu Li-Chun , Tsai Ya-Hui , Chou Yu-Ching , Jheng Ying-Chun , Lin Chi-Kang , Lyu Ning-Yuan , Chien Yueh , Yang Yi-Pin , Chang Kao-Jung , Chang Keng-Hao , Lee Yi-Liang , Wang Peng-Hui , Chu Ta-Wei , Chang Cheng-Chang
Published: August 2020

Background:

Cardiotocography is a common method of electronic fetal monitoring (EFM) for fetal well-being. Data-driven analyses have shown potential for automated EFM assessment. For this preliminary study, we used a novel artificial intelligence method based on fully convolutional networks (FCNs), with deep learning for EFM evaluation and correct recognition, and its possible role in evaluation of nonreassuring fetal status.

Methods:

We retrospectively collected 3239 EFM labor records from 292 deliveries and neonatal Apgar scores between December 2018 and July 2019 at a single medical center. We analyzed these data using an FCN model and compared the results with clinical practice.

Results:

The FCN model recognized EFM traces like physicians, with an average Cohen’s kappa coefficient of agreement of 0.525 and average area under the receiver operating characteristic curve of 0.892 for six fetal heart rate (FHR) categories. The FCN model showed higher sensitivity for predicting fetal compromise (0.528 vs 0.132) but a higher false-positive rate (0.632 vs 0.012) compared with clinical practice.

Conclusion:

FCN is a modern technique that may be useful for EFM trace recognition based on its multiconvolutional layered analysis. Our model showed a competitive ability to identify FHR patterns and the potential for evaluation of nonreassuring fetal status.
Prognosis After Weaning from Respiratory Extracorporeal Membrane Oxygenation
Authors: Yeo Hye Ju , Koo So-My , Han Junhee , Kim Junghyun , Hong Sang-Bum , Chung Chi Ryang , Park So Hee , Yong Park Seung , Sim Yun Su , Cho Young-Jae , Park Sunghoon , Kang Byung Ju , Oh Jin Young , Lee Sang-Min , Jung Jae-Seung , Chang Youjin , Yoo Jung-Wan , Cho Woo Hyun
Published: August 2020

Successful weaning from extracorporeal membrane oxygenation (ECMO) does not necessarily imply patient survival. We retrospectively analyzed 441 patients with acute respiratory failure from 16 hospitals in South Korea who underwent ECMO from January 2012 to December 2015. We evaluated the clinical factors associated with mortality after successful weaning from ECMO. Of all 441 patients, 245 (55.6%) were successfully weaned from ECMO. The majority of patients were initially supported with veno-venous ECMO (86.9%). Among those, 182 patients (41.3%) were discharged from hospital. Only 165 (37.4%) were alive after 6 months. Most cases of death occurred within the first month after weaning from ECMO (65%), and the most frequent reason for death was sepsis (76.2%). In the multivariate Cox regression analysis, patient age (per 10 years) (hazard ratio [HR] = 1.34, 95% CI = 1.12–1.61; p = 0.001), sequential organ failure assessment score (HR = 1.07, 95% CI = 1.02–1.13; p = 0.010), steroid (HR = 2.38, 95% CI = 1.27–4.45; p = 0.007), interstitial lung disease (HR = 1.20, 95% CI = 1.05–1.36; p = 0.006), and ECMO duration (per day) (HR = 1.02, 95% CI = 1.01–1.04; p < 0.001) were associated with the in-hospital mortality after weaning from ECMO. Furthermore, age (per 10 years) (HR = 1.45, 95% CI = 1.24–1.71; p < 0.001), steroid (HR = 2.19, 95% CI = 1.27–3.78; p = 0.005), and interstitial lung disease (HR = 1.16, 95% CI = 1.02–1.31; p = 0.021) were significantly associated with 6 month mortality. The prognosis after weaning from respiratory ECMO might be related to baseline conditions affecting the reversibility of the primary lung disease and to acquired infections.
Lessons From the Frontlines
Authors: Sagalowsky Selin Tuysuzoglu , Roskind Cindy Ganis , Fein Daniel M. , Teng David , Jamal Nazreen
Published: August 2020

The global pandemic novel coronavirus 2019 has upended healthcare and medical education, particularly in disease epicenters such as New York City. In this piece, we seek to describe the collective experiences and lessons learned by the New York City pediatric emergency medicine fellowship directors in clinical, educational, investigative, and psychological domains, in hopes of engendering conversation and informing future disaster response efforts.
The Inner Annulus Fibrosus Encroaches on the Nucleus Pulposus in the Injured Mouse Tail Intervertebral Disc
Authors: Wei Yulong , Tian Zuozhen , Tower Robert J. , E. Gullbrand Sarah , Yao Lutian , Shetye Snehal S. , Mauck Robert L. , Qin Ling , Zhang Yejia
Published: August 2020

Objective

The aim was to identify the source of cells within the center of the abnormal fibrocartilage tissue of the degenerative intervertebral disc after injury.

Design

Cross-breeding of mice with an inducible type II promoter collagen construct (Col2CreER) to Rosa26-TdTomato mice has been shown to result in Cre-recombinase activity and Tomato expression in inner annulus fibrosus cells after tamoxifen injection. To investigate the role of the inner annulus fibrosus in the intervertebral disc injury response, tail intervertebral discs of Col2CreER/tdTomato mice were punctured with a needle and examined 1–4 wks after injury. N-cadherin was examined by immunostaining.

Results

After the injury, the fibrocartilage in the degenerative intervertebral disc consisted of residual diseased nucleus pulposus cells and encroaching inner annulus fibrosus cells. The residual nucleus pulposus cells had lost their epithelial cell–like morphology and instead became oval shaped, with reduced adhesion to neighboring nucleus pulposus cells. This change in cellular morphology coincided with a loss of N-cadherin, which contributes to maintenance of healthy nucleus pulposus cell morphology. As expected, injured tail intervertebral discs showed reduced compressive properties as determined by biomechanical assessments.

Conclusions

The cellular composition of the degenerative intervertebral disc has been defined here, which is an important step in developing future treatments.
Familial Tuberculum Sellae Meningiomas
Authors: Zhou Peng , Wei Li , Shi Jia , Shao Naiyuan
Published: August 2020

Objectives:

The aim of this study was to study and explore the genetic mechanism of familial meningiomas through 3 cases of familial tuberculum sellae meningioma.

Methods:

A retrospective analysis of clinical data of 3 cases of familial tuberculum sellae meningioma patients, and the pathological results of types and immunohistochemical results of the 3 patients were compare.

Reults:

Three cases of postoperative pathology were meningiomas (mixed type), immunohistochemical examination showed that Vimentin, epithelial membrain antigen , and Ki67 were positive.

Conclusions:

The occurrence of meningiomas is associated with ≥1 chromosomal deletions, and the absence of certain tumor suppressor genes may be the genetic basis for the familial growth of meningiomas.
Cranioplasty for Skull Defect With Polypropylene Abdominal Wall Mesh
Authors: Abuzayed Bashar , Al-Abadi Husesein , Jamous Osama , Said Anas , Alawneh Khaled
Published: August 2020

Cranioplasty is a routine procedure in the practice in neurosurgery and craniofacial surgery. For the closure of the cranial defect, it may be difficult or impossible to split the bone sufficiently to obtain enough bone for complete closure of the defect in younger children. Thus, sometimes there is the need to use allografts, which may not be widely available in rural practice. We present 2 cases of cranioplasty with widely available and used polypropylene abdominal wall mesh. To add rigidity to the construct, the mesh was organized in a multilayered fashion. Postoperative follow-up showed good functional and cosmetic results.
Pre-Planned Cranioplasty Using Computer-Assisted Designed Temporalis Muscle Augmentation in Patients With Decompressive Craniectomy Involving Resection of the Temporalis Muscle
Authors: Park Gwangtae , Kim Jonghoon , Chang Chulhoon , Jung Youngjin
Published: August 2020

Background:

Decompressive craniectomy (DC) is the last-resort surgical procedure to reduce intracranial pressure and prevent secondary brain injury. Additional resection of the temporalis muscle and fascia can achieve a higher extracranial herniation volume compared to the standard DC technique at the expense of cosmetic problems for the patients. Various methods have been used to augment temporal fossa hollowing.

Methods:

To improve the cosmetic outcome, the authors report a patient who had a skull defect restored using a precisely shaped implant engineered via a computer using the opposite temporalis muscle as a mirror image. Polyether-ether-ketone cranioplasty was performed for the 52-year-old man with temporal hollowing after DC with resection of the temporalis muscle and fascia, due to a ruptured cerebral arteriovenous fistula.

Results:

The shape of the patient's surgical side was restored and not asymmetrical. The patient was very satisfied

Conclusion:

In the case of cranioplasty (CP) in patients with DC with resection of the temporalis muscle, CP with implants that include the opposite muscle may increase patient satisfaction without the risk of additional complications.
Bone Morophogenetic Protein Application as Grafting Materials for Bone Regeneration in Craniofacial Surgery: Current Application and Future Directions
Authors: Cicciù Marco , Fiorillo Luca , Cervino Gabriele , Habal Mutaz B.
Published: August 2020

Rebuilding atrophied alveolar ridges can present a significant challenge for the maxillofacial surgeons. A multitude of treatment options including guided bone regeneration, onlay block grafting, and distraction osteogenesis are today available as safe procedures.

The recent Food and Drug Administration approval of recombinant human bone morphogenetic proteins (rhBMPs) has given clinicians an added treatment option for reconstructing localized and large jaw defects. Currently, several patients have been successfully treated with the combination of bone graft and rhBMP-2 and the results have been documented as predictable and safe by clinical and radiologic examinations follow-up. In this study, a literature review was conducted using Medline, Medpilot, and Cochrane Database of Systematic Reviews. It was concentrated on manuscripts and overviews published in the last 20 years (2000–2020). The key terms employed were platelet-rich plasma, rhBMPs, and their combinations with the common scaffolds used for bone regeneration techniques. The results of clinical studies and animal trials were especially emphasized. The statements from the literature were compared with authors’ own clinical data.

The potential to reconstruct these large bone defects with a growth factor thus limiting or even avoiding a secondary harvest site is exciting and it represents a new frontier in the field of surgery. This study data confirm how there are excellent documents about the possible combination of using substitute materials and growth factor for treating large and minor craniofacial bone defects.
Relationship Between Health Care Spending and Clinical Outcomes in Bariatric Surgery
Authors: Chhabra Karan R. , Ghaferi Amir A. , Yang Jie , Thumma Jyothi R. , Dimick Justin B. , Tsai Thomas C.
Published: August 2020

Objective:

To evaluate sources of 90-day episode spending variation in Medicare patients undergoing bariatric surgery and whether spending variation was related to quality of care.

Summary of Background Data:

Medicare's bundled payments for care improvement-advanced program includes the first large-scale episodic bundling program for bariatric surgery. This voluntary program will pay bariatric programs a bonus if 90-day spending after surgery falls below a predetermined target. It is unclear what share of bariatric episode spending may be due to unnecessary variation and thus modifiable through care improvement.

Methods:

Retrospective analysis of fee-for-service Medicare claims data from 761 acute care hospitals providing inpatient bariatric surgery between January 1, 2011 and September 30, 2016. We measured associations between patient and hospital factors, clinical outcomes, and total Medicare spending for the 90-day bariatric surgery episode using multivariable regression models.

Results:

Of 64,537 patients, 46% underwent sleeve gastrectomy, 22% revisited the emergency department (ED) within 90 days, and 12.5% were readmitted. Average 90-day episode payments were $14,124, ranging from $12,220 at the lowest-spending quintile of hospitals to $16,887 at the highest-spending quintile. After risk adjustment, 90-day episode spending was $11,447 at the lowest quintile versus $15,380 at the highest quintile (difference $3932, P < 0.001). The largest components of spending variation were readmissions (44% of variation, or $2043 per episode), post-acute care (19% or $871), and index professional fees (15% or $450). The lowest spending hospitals had the lowest complication, ED visit, post-acute utilization, and readmission rates (P < 0.001).

Conclusions and Relevance:

In this retrospective analysis of Medicare patients undergoing bariatric surgery, the largest components of 90-day episode spending variation are readmissions, inpatient professional fees, and post-acute care utilization. Hospitals with lower spending were associated with lower rates of complications, ED visits, post-acute utilization, and readmissions. Incentives for improving outcomes and reducing spending seem to be well-aligned in Medicare's bundled payment initiative for bariatric surgery.
Surgical Outcomes After Neoadjuvant Chemoradiation Followed by Curative Surgery in Patients With Esophageal Cancer
Authors: von Holzen Urs , Schmidt Sven , Hayoz Stefanie , Steffen Thomas , Grieder Felix , Bartsch Detlef , Schnider Annelies , Knoefel Wolfram-Trudo , Piessen Guillaume , Kettelhack Christoph , Marti Walter R. , Schäfer Markus , Függer Reinhold , Köigsrainer Alfred , Gloor Beat , Furrer Markus , Gérard Marie-Aline , Hawle Hanne , Walz Martin K. , Alesina Piero , Ruhstaller Thomas
Published: August 2020

Objective:

To assess the impact of surgical technique in regard to morbidity and mortality after neoadjuvant treatment for esophageal cancer.

Background:

The SAKK trial 75/08 was a multicenter phase III trial (NCT01107639) comparing induction chemotherapy followed by chemoradiation and surgery in patients with locally advanced esophageal cancer.

Methods:

Patients in the control arm received induction chemotherapy with cisplatin and docetaxel, followed by concomitant chemoradiation therapy with cisplatin, docetaxel, and 45Gy. In the experimental arm, the same regimen was used with addition of cetuximab. After completion of neoadjuvant treatment, patients underwent esophagectomy. The experimental arm received adjuvant cetuximab. Surgical outcomes and complications were prospectively recorded and analyzed.

Results:

Total of 259 patients underwent esophagectomy. Overall complication rate was 56% and reoperation rate was 15% with no difference in complication rates for transthoracic versus transhiatal resections (56% vs 54%, P = 0.77), nor for video assisted thoracic surgeries (VATS) versus open transthoracic resections (67% vs 55%, P = 0.32). There was a trend to higher overall complication rates in squamous cell carcinoma versus adenocarcinoma (65% vs 51%, P = 0.035), and a significant difference in ARDS in squamous cell carcinoma with 14% versus 2% in adenocarcinoma (P = 0.0002). For patients with involved lymph nodes, a lymph node ratio of ≥0.1 was an independent predictor of PFS (HR 2.5, P = 0.01) and OS (HR 2.2, P = 0.03).

Conclusions:

This trial showed no difference in surgical complication rates between transthoracic and transhiatal resections. For patients with involved lymph nodes, lymph node ratio was an independent predictor of progression free survival and overall survival.
Lithium Use During Pregnancy in a Patient With Bipolar Disorder and Multiple Sclerosis
Authors: Lorettu Liliana , Carpita Barbara , Nivoli Alessandra , Milia Paolo , De Iorio Giovanni , Cremone Ivan Mirko , Dell'Osso Liliana
Published: August 2020

Although lithium is widely used as a first-line treatment for mood disorders, its mood-stabilizing effects remain not fully understood. A growing body of data are stressing that lithium seems to show broader properties, including neuroprotective effects. Lithium's ability to inhibit glycogen synthase kinase 3β, an enzyme that participates in the phosphorylation of τ, a microtubule-associated protein, stimulated interest in its possible therapeutic role in Alzheimer disease and other neurodegenerative disorders. Preliminary data also support exploration of lithium's potential therapeutic role in multiple sclerosis, an autoimmune disorder that is associated with co-occurring mood disorders. Lithium is associated with teratogenic risks to the developing fetus; however, recently revised downward estimates of its teratogenic risk of causing fetal cardiac malformation suggest that its potential therapeutic benefit to both mothers with bipolar disorder and their offspring should be considered in at least some cases. A 43-year-old woman previously diagnosed with bipolar disorder and MS was treated with lithium and thyroid hormone supplementation as her sole medications during her pregnancy. The patient remained euthymic throughout her pregnancy and over the course of her 5-year follow-up evaluations on this medication regimen. In addition to her stable mood, there has been no symptomatic progression or relapse of her MS, and her daughter continues to develop normally.

The case supports consideration of balancing lithium's mood-stabilizing benefit with its known teratogenic risk during pregnancy. The case also supports exploration of possible additional benefit in the context of MS co-occurring with bipolar disorder.
Key themes in recent research on interpersonal functioning in borderline personality disorder
Authors: Michael John , van Baal Simon
Published: August 2020

Purpose of review

We provide an overview of new ideas and directions of research on interpersonal functioning in borderline personality disorder (BPD).

Recent findings

We highlight the following key themes emerging in recent and ongoing research: investigation of the cognitive and motivational mechanisms which underpin impairments of interpersonal functioning in BPD, tracking BPD across the lifespan with earlier interventions and longitudinal studies, expansion of the scope of interest to family members of individuals with BPD and to people in the general population with levels of BPD traits, and investigating BPD online, not only by using internet-based testing platforms but also by studying the social media use of individuals with BPD.

The concise discussion of recent research on BPD provided here, together with the identification of key themes emerging from this work, provides a snapshot of ongoing work devoted to better understanding interpersonal functioning in borderline personality disorder.
Three-dimensionally preserved ‘Stage IIIb’ fossil down feather supports developmental modularity in feather evolution
Authors: Roy Arindam , Miller Case V. , Pittman Michael , Kaye Thomas G. , Peretti Adolf
Published: August 2020

We describe a unique three-dimensionally preserved fossil down feather from the Late Cretaceous of Myanmar. It’s morphology is highly congruent with Stage IIIb of the widely accepted Prum and Brush model of feather evolution-development. This makes the new specimen the first evidence of this developmental stage in the fossil record. The Stage IIIb diagnosis is robustly supported by the absence of a central rachis and by its paired barbules emanating from radially positioned barbs that are attached to a short calamus. Prum and Brush’s model hypothesises a bifurcation in the evolution-development pathway at Stage III. Stage IIIa involves rachis development and branching into barbs. Stage IIIb involves branching of the barbs from the calamus and then further branching of the barbules from the barbs. These two pathways then converge into Stage IIIa+b where feathers produce a rachis, barbs and barbules in nested order, finally leading to Stage IV. Evolution-development studies on the morphogenesis of feathers have unequivocally shown that such feather branching can be controlled by BMP, Noggin, Shh and several other proteins. Therefore, molecular crosstalk can convert a barb into a rachis and vice versa. The topology of this down feather, consistent with specific patterns of modular protein-protein signalling already observed, provides the first definitive evidence that such signalling was responsible for the evolution of a diverse inventory of feather morphologies in non-avialan dinosaurs and early birds since the middle Jurassic.
Novel two-component system-like elements reveal functional domains associated with restriction-modification systems and paraMORC ATPases in bacteria
Authors: Bellieny-Rabelo Daniel , Pretorius Willem JS , Moleleki Lucy N
Published: August 2020

Background

Two-component systems (TCS) are essential machineries allowing for efficient signal recognition and transmission in bacterial cells. The majority of TCSs utilized by bacteria are composed by a sensor histidine kinase (HK) and a cognate response regulator (RR). In the present study, we report two newly predicted protein domains — Response_reg_2 (PF19192) and HEF_HK (PF19191) — in bacteria which exhibit high structural similarity, respectively, with typical domains of RRs and HKs.

Results

Additionally, the genes encoding for the novel predicted domains exhibit a 91.6% linkage observed across 644 genomic regions recovered from 628 different bacterial strains. The remarkable adjacent co-localization between genes carrying Response_reg_2 and HEF_HK in addition to their conserved structural features, which are highly similar to those from well-known HKs and RRs, raises the possibility of Response_reg_2 and HEF_HK integrating a new TCS in bacteria. The genomic regions in which these predicted two-component systems-like are located additionally exhibit an overrepresented presence of restriction-modification (R-M) systems especially the type II R-M. Among these, there is a conspicuous presence of C-5 cytosine-specific DNA methylases which may indicate a functional association with the newly discovered domains. The solid presence of R-M systems and the presence of the GHKL family domain HATPase_c_3 across most of the HEF_HK-containing genes are also indicative that these genes are evolutionarily related to the paraMORC family of ATPases.

Conclusions

The present study uncovered two novel protein conserved domains and raised the possibility of a TCS-like system undertaking a regulatory role mechanistically linked to R-M systems in a large variety of bacterial lineages.
Fine-scale landscape genetics unveiling contemporary asymmetric movement of red panda (Ailurus fulgens) in Kangchenjunga landscape, India
Authors: Dalui Supriyo , Khatri Hiren , Singh Sujeet Kumar , Basu Shambadeb , Ghosh Avijit , Mukherjee Tanoy , Sharma Lalit Kumar , Singh Randeep , Chandra Kailash , Thakur Mukesh
Published: August 2020

Wildlife management in rapid changing landscapes requires critical planning through cross cutting networks, and understanding of landscape features, often affected by the anthropogenic activities. The present study demonstrates fine-scale spatial patterns of genetic variation and contemporary gene flow of red panda (Ailurus fulgens) populations with respect to landscape connectivity in Kangchenjunga Landscape (KL), India. The study found about 1309.54 Km2area suitable for red panda in KL-India, of which 62.21% area fell under the Protected Area network. We identified 24 unique individuals from 234 feces collected at nine microsatellite loci. The spatially explicit and non-explicit Bayesian clustering algorithms evident to exhibit population structuring and supported red panda populations to exist in meta-population frame work. In concurrence to the habitat suitability and landscape connectivity models, gene flow results supported a contemporary asymmetric movement of red panda by connecting KL- India in a crescent arc. We demonstrate the structural-operational connectivity of corridors in KL-India that facilitated red panda movement in the past. We also seek for cooperation in Nepal, Bhutan and China to aid in preparing for a comprehensive monitoring plan for the long-term conservation and management of red panda in trans-boundary landscapes.
KRSA: Network-based Prediction of Differential Kinase Activity from Kinome Array Data
Authors: DePasquale Erica A. K. , Alganem Khaled , Bentea Eduard , Nawreen Nawshaba , McGuire Jennifer L. , Naji Faris , Hilhorst Riet , Meller Jaroslaw , McCullumsmith Robert E.
Published: August 2020

Motivation

Phosphorylation by serine-threonine and tyrosine kinases is critical for determining protein function. Array-based approaches for measuring multiple kinases allow for the testing of differential phosphorylation between conditions for distinct sub-kinomes. While bioinformatics tools exist for processing and analyzing such kinome array data, current open-source tools lack the automated approach of upstream kinase prediction and network modeling. The presented tool, alongside other tools and methods designed for gene expression and protein-protein interaction network analyses, help the user better understand the complex regulation of gene and protein activities that forms biological systems and cellular signaling networks.

Results

We present the Kinome Random Sampling Analyzer (KRSA), a web-application for kinome array analysis. While the underlying algorithm has been experimentally validated in previous publications, we tested the full KRSA application on dorsolateral prefrontal cortex (DLPFC) in male (n=3) and female (n=3) subjects to identify differential phosphorylation and upstream kinase activity. Kinase activity differences between males and females were compared to a previously published kinome dataset (11 female and 7 male subjects) which showed similar patterns to the global phosphorylation signal. Additionally, kinase hits were compared to gene expression databases forin silicovalidation at the transcript level and showed differential gene expression of kinases.

Availability and implementation

KRSA as a web-based application can be found athttp://bpg-n.utoledo.edu:3838/CDRL/KRSA/. The code and data are available athttps://github.com/kalganem/KRSA.

Supplementary information

Supplementary data are available online.
Imaging the Transmembrane and Transendothelial Sodium Gradients in Gliomas
Authors: Khan Muhammad H. , Walsh John J. , Mihailović Jelena M. , Mishra Sandeep K. , Coman Daniel , Hyder Fahmeed
Published: August 2020

High sodium (Na+) in extracellular (Na+e) and blood (Na+b) compartments and low Na+in intracellular milieu (Na+i) produce strong transmembrane (ΔNa+mem) and weak transendothelial (ΔNa+end) gradients respectively, which reflect cell membrane potential (Vm) and blood-brain barrier (BBB) integrity. We developed a sodium (23Na) magnetic resonance spectroscopic imaging (MRSI) method using an intravenously-administered paramagnetic contrast agent to measure ΔNa+memand ΔNa+end.In vitro23Na-MRSI established that the23Na signal is strongly shifted by the agent compared to biological factors.In vivo23Na-MRSI showed Na+iremained unshifted and Na+bwas more shifted than Na+e, and these together created weakened ΔNa+memand enhanced ΔNa+endin rat gliomas. Specifically, RG2 and U87 tumors maintained weakened ΔNa+mem(i.e., depolarizedVm) implying an aggressive state for proliferation, and RG2 tumors displayed elevated ΔNa+endsuggesting altered BBB integrity.23Na-MRSI will allow explorations of perturbed Na+homeostasisin vivofor the tumor neurovascular unit.
Bidirectional interconversion between mutually exclusive tumorigenic and drug-tolerant melanoma cell phenotypes
Authors: Zhang Yuntian , Belote Rachel L , Urquijo Marcus A , Hansen Maike M. K. , Hejna Miroslav , Moustafa Tarek E. , Liu Tong , Lange Devin , Vand-Rajabpour Fatemeh , Chang Matthew , Lohman Brian K. , Stubben Chris , Zhang Xiaoyang , Weinberger Leor S. , VanBrocklin Matthew W , Grossman Douglas , Lex Alexander , Kulkarni Rajan , Zangle Thomas , Judson-Torres Robert L.
Published: August 2020

Human cancers can exhibit phenotype switching, resulting in cells that are more metastatic or that are more tolerant to treatment. However, the relationship between these aggressive states is not well understood. We investigated the dynamics of phenotypic switching in human melanoma cells by monitoring the fluorescent activity from a transgenic reporter of BRN2 promoter activation. Melanoma cells exhibit heterogeneous BRN2 expression patterns that are reestablished upon isolation and clonal outgrowth. Specifically, stable BRN2 expression was generally inherited over multiple generations while undergoing occasional bidirectional interconversion. We found that BRN2 low cells were required for tumor initiation and metastasis in animal engraftment assays but were more sensitive to targeted BRAF inhibition. In contrast, the BRN2 high state was not tumorigenic, but entry into this state was uniform and persistent among cells tolerant to targeted BRAF therapy. Single-cell RNA sequencing analyses revealed core programs exclusive to either the BRN2 high or low cells, each of which is present inex vivotumors, demonstrating the physiological relevance of these states. Our findings emphasize that one challenge of effectively targeting phenotype switching in melanoma as a therapeutic strategy could be balancing distinct aggressive phenotypes so that sensitizing tumors to BRAF inhibition does not inadvertently lead to further dissemination.

Teaser

Unraveling melanoma’s shape-shifting behavior: insights into how cancer cells swap between metastasis and drug evasion.