bluuebunny/crossref_metadata_2025 huggingface dataset:
Human body-fluid proteome: quantitative profiling and computational prediction
Authors: Huang Lan , Shao Dan , Wang Yan , Cui Xueteng , Li Yufei , Chen Qian , Cui Juan
Published: November 2019

Empowered by the advancement of high-throughput bio technologies, recent research on body-fluid proteomes has led to the discoveries of numerous novel disease biomarkers and therapeutic drugs. In the meantime, a tremendous progress in disclosing the body-fluid proteomes was made, resulting in a collection of over 15 000 different proteins detected in major human body fluids. However, common challenges remain with current proteomics technologies about how to effectively handle the large variety of protein modifications in those fluids. To this end, computational effort utilizing statistical and machine-learning approaches has shown early successes in identifying biomarker proteins in specific human diseases. In this article, we first summarized the experimental progresses using a combination of conventional and high-throughput technologies, along with the major discoveries, and focused on current research status of 16 types of body-fluid proteins. Next, the emerging computational work on protein prediction based on support vector machine, ranking algorithm, and protein–protein interaction network were also surveyed, followed by algorithm and application discussion. At last, we discuss additional critical concerns about these topics and close the review by providing future perspectives especially toward the realization of clinical disease biomarker discovery.
SCOT: Rethinking the classification of secondary structure elements
Authors: Brinkjost Tobias , Ehrt Christiane , Koch Oliver , Mutzel Petra
Published: November 2019

Motivation

Secondary structure classification is one of the most important issues in structure-based analyses due to its impact on secondary structure prediction, structural alignment and protein visualization. There are still open challenges concerning helix and sheet assignments which are currently not addressed by a single multi-purpose software.

Results

We introduce SCOT (Secondary structure Classification On Turns) as a novel secondary structure element assignment software which supports the assignment of turns, right-handed α-, 310- and π-helices, left-handed α- and 310-helices, 2.27- and polyproline II helices, β-sheets and kinks. We demonstrate that the introduction of helix Purity values enables a clear differentiation between helix classes. SCOT’s unique strengths are highlighted by comparing it to six state-of-the-art methods (DSSP, STRIDE, ASSP, SEGNO, DISICL and SHAFT). The assignment approaches were compared concerning geometric consistency, protein structure quality and flexibility dependency and their impact on secondary structure element-based structural alignments. We show that only SCOT’s combination of hydrogen bonds, geometric criteria and dihedral angles enables robust assignments independent of the structure quality and flexibility. We demonstrate that this combination and the elaborate kink detection lead to SCOT’s clear superiority for protein alignments. As the resulting helices and strands are provided in a PDB conform output format, they can immediately be used for structure alignment algorithms. Taken together, the application of our new method and the straight-forward visualization using the accompanying PyMOL scripts enable the comprehensive analysis of regular backbone geometries in proteins.

Availability and implementation

https://this-group.rocks

Supplementary information

Supplementary data are available at Bioinformatics online.
KofamKOALA: KEGG Ortholog assignment based on profile HMM and adaptive score threshold
Authors: Aramaki Takuya , Blanc-Mathieu Romain , Endo Hisashi , Ohkubo Koichi , Kanehisa Minoru , Goto Susumu , Ogata Hiroyuki
Published: November 2019

KofamKOALA is a web server to assign KEGG Orthologs (KOs) to protein sequences by homology search against a database of profile hidden Markov models (KOfam) with pre-computed adaptive score thresholds. KofamKOALA is faster than existing KO assignment tools with its accuracy being comparable to the best performing tools. Function annotation by KofamKOALA helps linking genes to KEGG resources such as the KEGG pathway maps and facilitates molecular network reconstruction.

Availability and implementation

KofamKOALA, KofamScan and KOfam are freely available from GenomeNet (https://www.genome.jp/tools/kofamkoala/).

Supplementary information

Supplementary data are available at Bioinformatics online.
Absence of TRIM32 Leads to Reduced GABAergic Interneuron Generation and Autism-like Behaviors in Mice via Suppressing mTOR Signaling
Authors: Zhu Jian-Wei , Zou Ming-Ming , Li Yi-Fei , Chen Wen-Jin , Liu Ji-Chuan , Chen Hong , Fang Li-Pao , Zhang Yan , Wang Zhao-Tao , Chen Ji-Bo , Huang Wenhui , Li Shen , Jia Wei-Qiang , Wang Qin-Qin , Zhen Xue-Chu , Liu Chun-Feng , Li Shao , Xiao Zhi-Cheng , Xu Guo-Qiang , Schwamborn Jens C , Schachner Melitta , Ma Quan-Hong , Xu Ru-Xiang
Published: November 2019

Mammalian target of rapamycin (mTOR) signaling plays essential roles in brain development. Hyperactive mTOR is an essential pathological mechanism in autism spectrum disorder (ASD). Here, we show that tripartite motif protein 32 (TRIM32), as a maintainer of mTOR activity through promoting the proteasomal degradation of G protein signaling protein 10 (RGS10), regulates the proliferation of medial/lateral ganglionic eminence (M/LGE) progenitors. Deficiency of TRIM32 results in an impaired generation of GABAergic interneurons and autism-like behaviors in mice, concomitant with an elevated autophagy, which can be rescued by treatment embryonically with 3BDO, an mTOR activator. Transplantation of M/LGE progenitors or treatment postnatally with clonazepam, an agonist of the GABAA receptor, rescues the hyperexcitability and the autistic behaviors of TRIM32−/− mice, indicating a causal contribution of GABAergic disinhibition. Thus, the present study suggests a novel mechanism for ASD etiology in that TRIM32 deficiency-caused hypoactive mTOR, which is linked to an elevated autophagy, leads to autism-like behaviors via impairing generation of GABAergic interneurons. TRIM32−/− mouse is a novel autism model mouse.
Mesophotic.org: a repository for scientific information on mesophotic ecosystems
Authors: Bongaerts Pim , Perez-Rosales Gonzalo , Radice Veronica Z , Eyal Gal , Gori Andrea , Gress Erika , Hammerman Nicholas M , Hernandez-Agreda Alejandra , Laverick Jack , Muir Paul , Pinheiro Hudson , Pyle Richard L , Rocha Luiz , Turner Joseph A , Booker Ryan
Published: November 2019

Mesophotic coral ecosystems (MCEs) and temperate mesophotic ecosystems (TMEs) occur at depths of roughly 30–150 m depth and are characterized by the presence of photosynthetic organisms despite reduced light availability. Exploration of these ecosystems dates back several decades, but our knowledge remained extremely limited until about a decade ago, when a renewed interest resulted in the establishment of a rapidly growing research community. Here, we present the ‘mesophotic.org’ database, a comprehensive and curated repository of scientific literature on mesophotic ecosystems. Through both manually curated and automatically extracted metadata, the repository facilitates rapid retrieval of available information about particular topics (e.g. taxa or geographic regions), exploration of spatial/temporal trends in research and identification of knowledge gaps. The repository can be queried to comprehensively obtain available data to address large-scale questions and guide future research directions. Overall, the ‘mesophotic.org’ repository provides an independent and open-source platform for the ever-growing research community working on MCEs and TMEs to collate and expedite our understanding of the occurrence, composition and functioning of these ecosystems.

Database URL: http://mesophotic.org/
AcetoBase: a functional gene repository and database for formyltetrahydrofolate synthetase sequences
Authors: Singh Abhijeet , Müller Bettina , Fuxelius Hans-Henrik , Schnürer Anna
Published: November 2019

Acetogenic bacteria are imperative to environmental carbon cycling and diverse biotechnological applications, but their extensive physiological and taxonomical diversity is an impediment to systematic taxonomic studies. Acetogens are chemolithoautotrophic bacteria that perform reductive carbon fixation under anaerobic conditions through the Wood–Ljungdahl pathway (WLP)/acetyl-coenzyme A pathway. The gene-encoding formyltetrahydrofolate synthetase (FTHFS), a key enzyme of this pathway, is highly conserved and can be used as a molecular marker to probe acetogenic communities. However, there is a lack of systematic collection of FTHFS sequence data at nucleotide and protein levels. In an attempt to streamline investigations on acetogens, we developed AcetoBase - a repository and database for systematically collecting and organizing information related to FTHFS sequences. AcetoBase also provides an opportunity to submit data and obtain accession numbers, perform homology searches for sequence identification and access a customized blast database of submitted sequences. AcetoBase provides the prospect to identify potential acetogenic bacteria, based on metadata information related to genome content and the WLP, supplemented with FTHFS sequence accessions, and can be an important tool in the study of acetogenic communities. AcetoBase can be publicly accessed at https://acetobase.molbio.slu.se.
Left atrial strain: a multi-modality, multi-vendor comparison study
Authors: Pathan Faraz , Zainal Abidin Hafisyatul Aiza , Vo Quang Ha , Zhou Hui , D’Angelo Tommaso , Elen Elen , Negishi Kazuaki , Puntmann Valentina O , Marwick Thomas H , Nagel Eike
Published: November 2019

Aims

Left atrial (LA) strain is a prognostic biomarker with utility across a spectrum of acute and chronic cardiovascular pathologies. There are limited data on intervendor differences and no data on intermodality differences for LA strain. We sought to compare the intervendor and intermodality differences between transthoracic echocardiography (TTE) and cardiac magnetic resonance (CMR) derived LA strain. We hypothesized that various components of atrial strain would show good intervendor and intermodality correlation but that there would be systematic differences between vendors and modalities.

Methods and results

We evaluated 54 subjects (43 patients with a clinical indication for CMR and 11 healthy volunteers) in a study comparing TTE- and CMR-derived LA reservoir strain (ƐR), conduit strain (ƐCD), and contractile strain (ƐCT). The LA strain components were evaluated using four dedicated types of post-processing software. We evaluated the correlation and systematic bias between modalities and within each modality. Intervendor and intermodality correlation was: ƐR [intraclass correlation coefficient (ICC 0.64–0.90)], ƐCD (ICC 0.62–0.89), and ƐCT (ICC 0.58–0.77). There was evidence of systematic bias between vendors and modalities with mean differences ranging from (3.1–12.2%) for ƐR, ƐCD (1.6–8.6%), and ƐCT (0.3–3.6%). Reproducibility analysis revealed intraobserver coefficient of variance (COV) of 6.5–14.6% and interobserver COV of 9.9–18.7%.

Conclusion

Vendor derived ƐR, ƐCD, and ƐCT demonstrates modest to excellent intervendor and intermodality correlation depending on strain component examined. There are systematic differences in measurements depending on modality and vendor. These differences may be addressed by future studies, which, examine calibration of LA geometry/higher frame rate imaging, semi-quantitative approaches, and improvements in reproducibility.
Gut Microbiota: From the Forgotten Organ to a Potential Key Player in the Pathology of Alzheimer’s Disease
Authors: Seo Dong-Oh , Holtzman David M
Published: November 2019

More than 300 years ago, Antony van Leewenhoeck first described observing single-celled microorganisms, which he termed “animalcules,” examining his saliva under a microscope. Although the idea of the coexistence of microorganisms in our body is not new, we have only recently been able to investigate their ecological relationship to our body, with the development of high-throughput molecular techniques. The diverse microorganism communities residing in our guts are established and maintained by complex interactions among microorganisms and their host. Notably, their alteration has been implicated in influencing various diseases including neurological diseases. Alzheimer’s disease (AD) is the most common cause of dementia characterized by a progressive decline in memory and thinking severe enough to interfere with daily life. Despite the great progress in linking genetic risk factors with AD pathogenesis, treatments targeted at AD pathology and its modifiers have not yet resulted in a disease-modifying therapy. There is mounting evidence that the gut microbiota interacts with AD pathogenesis by disrupting neuroinflammation and metabolic homeostasis—the gut microbiota has gone from being the forgotten organ to a potential key player in the AD pathology.
Trochodendron aralioides, the first chromosome-level draft genome in Trochodendrales and a valuable resource for basal eudicot research
Authors: Strijk Joeri S , Hinsinger Damien D , Zhang Fengping , Cao Kunfang
Published: November 2019

Background

The wheel tree (Trochodendron aralioides) is one of only 2 species in the basal eudicot order Trochodendrales. Together with Tetracentron sinense, the family is unique in having secondary xylem without vessel elements, long considered to be a primitive character also found in Amborella and Winteraceae. Recent studies however have shown that Trochodendraceae belong to basal eudicots and demonstrate that this represents an evolutionary reversal for the group. Trochodendron aralioides is widespread in cultivation and popular for use in gardens and parks.

Findings

We assembled the T. aralioides genome using a total of 679.56 Gb of clean reads that were generated using both Pacific Biosciences and Illumina short-reads in combination with 10XGenomics and Hi-C data. Nineteen scaffolds corresponding to 19 chromosomes were assembled to a final size of 1.614 Gb with a scaffold N50 of 73.37 Mb in addition to 1,534 contigs. Repeat sequences accounted for 64.226% of the genome, and 35,328 protein-coding genes with an average of 5.09 exons per gene were annotated using de novo, RNA-sequencing, and homology-based approaches. According to a phylogenetic analysis of protein-coding genes, T. aralioides diverged in a basal position relative to core eudicots, ~121.8–125.8 million years ago.

Conclusions

Trochodendron aralioides is the first chromosome-scale genome assembled in the order Trochodendrales. It represents the largest genome assembled to date in the basal eudicot grade, as well as the closest order relative to the core-eudicots, as the position of Buxales remains unresolved. This genome will support further studies of wood morphology and floral evolution, and will be an essential resource for understanding rapid changes that took place at the base of the Eudicot tree. Finally, it can further genome-assisted improvement for cultivation and conservation efforts of the wheel tree.
Extinction risk and conservation of critically endangered angel sharks in the Eastern Atlantic and Mediterranean Sea
Authors: Lawson Julia M , Pollom Riley A , Gordon Cat A , Barker Joanna , Meyers Eva K M , Zidowitz Heike , Ellis Jim R , Bartolí Álex , Morey Gabriel , Fowler Sarah L , Alvarado David Jiménez , Fordham Sonja V , Sharp Rowland , Hood Ali R , Dulvy Nicholas K
Published: November 2019

Understanding the details of local and regional extinctions allows for more efficient allocation of conservation activities and resources. This involves identifying where populations persist, where populations may still be present, and where populations may be locally extinct. Three threatened angel sharks occur in the Eastern Atlantic and Mediterranean Sea: Sawback Angelshark (Squatina aculeata), Smoothback Angelshark (Squatina oculata), and Angelshark (Squatina squatina). Population sizes and geographic ranges of these species have been reduced due to overfishing and habitat loss, placing them among the world s most threatened chondrichthyans. We revise distribution maps, review global status, and present a Conservation Strategy to protect and restore these angel shark populations by minimizing fishing mortality, protecting critical habitat, and mitigating human disturbance. Updated distributions reveal that a halving of the geographic extent may have occurred for all three species, with potential declines of 51% for Sawback Angelshark, 48% for Smoothback Angelshark, and 58% for Angelshark. While 20 national and international management measures are now in place for Angelshark, only half of these include the other two species. We encourage further conservation action to adopt and develop this Conservation Strategy to restore angel shark populations to robust levels and safeguard them throughout their range.
Aortic calcifications on routine preoperative chest X-ray and perioperative stroke during cardiac surgery: a nested matched case–control study
Authors: Knol Wiebe G , Bogers Ad J J C , Braun Loes M M , van Rosmalen Joost , Bekker Margreet W A , Krestin Gabriel P , Budde Ricardo P J
Published: November 2019

OBJECTIVES

Perioperative stroke in cardiac surgery is most often embolic in origin. Preoperative chest X-ray (CXR) is routinely used amongst others to screen for relevant aortic calcification, a potential source of embolic stroke. We performed a nested matched case–control study to examine the relationship between aortic calcifications on CXR and the occurrence of embolic stroke.

METHODS

Among all consecutive patients undergoing cardiac surgery in our hospital between January 2014 and July 2017, we selected all patients with perioperative embolic stroke (cases). Controls, all patients without perioperative stroke, were matched on age, sex and type of surgery. All preoperative CXRs were scored for aortic calcifications (none, mild, severe) in the ascending aorta, arch, aortic knob and descending aorta.

RESULTS

Out of the 3038 eligible patients, 27 cases were detected and 78 controls were selected. In the stroke group, mild-to-severe calcifications were found least often in the ascending aorta [9% of patients, 95% confidence interval (CI) 1–29%] and most frequently in the aortic knob (63% of patients, 95% CI 44–78%). The distribution of aortic calcification was comparable in cases versus controls.

CONCLUSIONS

Calcification burden was comparable between the cases and their matched controls. In our study population, CXR findings on aortic calcification were not related to the risk of embolic stroke. In these patients, the correlation between findings on the preoperative CXR and the risk of stroke might, therefore, be too weak to use the CXR directly for the assessment of the safety of manipulating the ascending aorta during surgery.
𝒦-convergence as a new tool in numerical analysis
Authors: Feireisl Eduard , Lukáčová-Medviďová Mária , Mizerová Hana
Published: November 2019

We adapt the concept of $\mathscr{K}$-convergence of Young measures to the sequences of approximate solutions resulting from numerical schemes. We obtain new results on pointwise convergence of numerical solutions in the case when solutions of the limit continuous problem possess minimal regularity. We apply the abstract theory to a finite volume method for the isentropic Euler system describing the motion of a compressible inviscid fluid. The result can be seen as a nonlinear version of the fundamental Lax equivalence theorem.
How It Can Save the World
Authors: Bardell Alex
Published: November 2019

Today is an exciting time in the world of technology, writes Alex Bardell MBCS, Sustainable Technology Advocate, Enterprise Architect and member of the BCS Green IT Specialist Group. We have an array of ideas establishing themselves as viable products, but is this drive for innovation sustainable?
Trust and Responsibility the Fujitsu Way
Authors: Hamilton Johanna
Published: November 2019

In a suburb of Kawasaki, on the outskirts of Tokyo, a gentle Pacific breeze rustles ancient cherry trees, scattering their red and golden leaves across ponds of Koi carp. Is this the site of the 900-year-old Daishi Temple? No, writes Johanna Hamilton AMBCS, this is the very first Fujitsu factory.
What is the Future of the Chief Sustainability Officer?
Authors: Bardell Alex
Published: November 2019

There is a business function to deliver sustainability either as an individual or as a team, writes Alex Bardell MBCS of the Green IT Specialist Group – but with increased awareness of environmental issues, is this role still required?
New BCS Office: Grand Opening
Authors: Melsom Blair
Published: November 2019

BCS London was officially opened by the Lord Mayor of the City of London, Alderman Peter Estlin on 21st October 2019. Blair Melsom AMBCS attended to find out more
Cyber Attacks and How to Buy Time
Authors: Folini Christian
Published: November 2019

Author of the ModSecurity Handbook and co-lead of the OWASP ModSecurity Core Rule Set project, Christian Folini explains why open source software is the most e ective way to add security to web application services
Can AI Overcome the Project Delivery Problem?
Authors: Skinner Lloyd J
Published: November 2019

Project management is a complex business, involving many technical processes and human variables. Lloyd J. Skinner, Chief Executive Officer at Greyfly, asks whether artificial intelligence is the project panacea we’ve been waiting for.
Prediction of dolutegravir pharmacokinetics and dose optimization in neonates via physiologically based pharmacokinetic (PBPK) modelling
Authors: Bunglawala Fazila , Rajoli Rajith K R , Mirochnick Mark , Owen Andrew , Siccardi Marco
Published: November 2019

Background

Only a few antiretroviral drugs (ARVs) are recommended for use during the neonatal period and there is a need for more to be approved to increase treatment and prophylaxis strategies. Dolutegravir, a selective integrase inhibitor, has potential for treatment of HIV infection and prophylaxis of transmission in neonates.

Objectives

To model the pharmacokinetics of dolutegravir in neonates and to simulate a theoretical optimal dosing regimen.

Methods

The physiologically based pharmacokinetic (PBPK) model was built incorporating the age-related changes observed in neonates. Virtual neonates between 0 and 28 days were simulated. The model was validated against observed clinical data for raltegravir and midazolam in neonates, prior to the prediction of dolutegravir pharmacokinetics.

Results

Both raltegravir and midazolam passed the criteria for model qualification, with simulated data within 1.8-fold of clinical data. The qualified model predicted the pharmacokinetics for several multidose regimens of dolutegravir. Regimen 6 involved 5 mg doses with a 48 h interval from Day 1–20, increasing to 5 mg once daily on Week 3, yielding AUC and Ctrough values of 37.2 mg·h/L and 1.3 mg/L, respectively. These exposures are consistent with those observed in paediatric patients receiving dolutegravir.

Conclusions

Dolutegravir pharmacokinetics were successfully simulated in the neonatal PBPK model. The predictions suggest that during the first 3 weeks of life a 5 mg dose administered every 48 h may achieve plasma exposures needed for therapy and prophylaxis.
Characterization of water intake and water efficiency in beef cattle1,2
Authors: Ahlberg Cashley M , Allwardt Kristi , Broocks Ashley , Bruno Kelsey , Taylor Alexandra , Mcphillips Levi , Krehbiel Clint R , Calvo-Lorenzo Michelle , Richards Chris J , Place Sara E , Desilva Udaya , Vanoverbeke Deborah L , Mateescu Raluca G , Kuehn Larry A , Weaber Robert , Bormann Jennifer , Rolf Megan M
Published: November 2019

In the future, water may not be as readily available due to increases in competition from a growing human population, wildlife, and other agricultural sectors, making selection for water efficiency of beef cattle increasingly important. Substantial selection emphasis has recently been placed on feed efficiency in an effort to reduce production costs, but no emphasis has been placed on making cattle more water efficient due to lack of data. Thus, the objective of this study was to calculate water efficiency metrics for cattle and evaluate their relationship to growth, feed intake (FI), and feed efficiency. Individual daily FI and water intake (WI) records were collected on 578 crossbred steers over a 70-d test period. Animals with low water intake ate less feed, had lower gains, and were more water efficient (as defined by water to gain ratio, W/G, and residual water intake, RWI). However, the amount of water consumed by animals had minimal phenotypic relationship with feed efficiency (residual feed intake [RFI], R2 = 0.1050 and feed to gain ratio (F/G) ratio R2 = 0.0726). Cattle that had low DMI consumed less water, had lower gains, had lower RFI, and had higher F/G. The level of feed consumed had minimal relationship with water efficiency. WI, W/G, RWI, and ADG had moderate heritability estimates of 0.39, 0.39, 0.37, and 0.37, respectively. High heritability estimates were observed for DMI and RFI (0.67 and 0.65, respectively). Feed to gain had a low heritability estimate of 0.16. WI had a strong positive genetic correlation with W/G (0.99) and RWI (0.88), thus selecting for decreased WI should also make cattle more water efficient. The genetic correlation between WI and ADG was 0.05; thus, selecting for low WI cattle should have little effect on growth. There is a low to moderate genetic correlation between WI and DMI (0.34). RWI has a positive genetic correlation with W/G ratio (0.89) and F/G ratio (0.42) and is negatively genetically correlated with RFI (−0.57). Water to gain and F/G had a strong positive genetic correlation (0.68). RFI has a positive genetic correlation with W/G ratio (0.37) and F/G (0.88). Minimal antagonisms seem to be present between WI and ADG, although it should be noted that standard errors were large and often not significantly different from zero due to the small sample size. However, care should be taken to ensure that unintended changes do not occur in DMI or other production traits and incorporation of WI into a selection index would likely prove to be the most effective method for selection.
Factors Associated with Attrition of Adult Participants in a Longitudinal Database: A National Institute on Disability, Independent Living, and Rehabilitation Research Burn Model System Study
Authors: Bamer Alyssa M , McMullen Kara , Gibran Nicole , Holavanahalli Radha , Schneider Jeffrey C , Carrougher Gretchen J , Wiechman Shelley , Wolfe Audrey , Amtmann Dagmar
Published: November 2019

Participant attrition in longitudinal studies can lead to substantial bias in study results, especially when attrition is nonrandom. A previous study of the Burn Model System (BMS) database prior to 2002 identified participant and study-related factors related to attrition. The purpose of the current study was to examine changes in attrition rates in the BMS longitudinal database since 2002 and to revisit factors associated with attrition. Individuals 18 years and older enrolled in the BMS database between 2002 and 2018 were included in this study. Stepwise logistic regression models identified factors significantly associated with attrition at 6, 12, and 24 months postburn injury. The percentage of individuals lost to follow-up was 26% at 6 months, 33% at 12 months, and 42% at 24 months. Factors associated with increased risk of loss to follow-up across two or more time points include male sex, lower TBSA burn size, being unemployed at the time of burn, shorter duration of acute hospital stay, younger age, not having private health insurance or workers’ compensation, and a history of drug abuse. Retention levels in the BMS have improved by at least 10% at all time points since 2002. The BMS and other longitudinal burn research projects can use these results to identify individuals at high risk for attrition who may require additional retention efforts. Results also indicate potential sources of bias in research projects utilizing the BMS database.
Role of arthroscopy for the diagnosis and management of post-traumatic hip pain: a prospective study
Authors: Alfikey Arafat , El-Bakoury Ahmed , Karim Mahmoud Abdel , Farouk Hazem , Kaddah Mohamed Abdelhalem , Abdelazeem Ahmed Hazem
Published: November 2019

The current published literature regarding the role of hip arthroscopy in the diagnosis and management of post-traumatic hip pain is still limited. Therefore, we conducted the present prospective study to determine the value of hip arthroscopy in the diagnosis and management of various causes of hip pain after traumatic conditions. The present study included a prospective cohort of 17 patients with symptomatic post-traumatic hip pain. It was conducted between July 2013 and May 2018. The mean age was 22 (19–29) years and the mean follow-up was 24 (r: 7–36) months. Prior to surgery, every eligible patient underwent assessment of functional status using the Modified Harris Hip Score, Oxford hip score (OHS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) score. All patients underwent arthroscopic management for their diagnosed pathologies. The most commonly encountered diagnosis was labral tear (58.8%), followed by ligamentum teres tear (35.3%) and loose intra-articular fragments (29.4%). In addition, 52.9% of the patients had associated CAM lesion and 11.8% had associated Pincer lesion. The mHSS, OHS and WOMAC score showed significant improvement in the post-operative period (P < 0.001), all the 17 patients had 100% Patient Acceptable Symptomatic State; only one patient did not achieve minimal clinical importance difference. One case underwent labral debridement for failed labral repair (5.8%), another patient developed maralgia paraesthetica (5.8%). In conclusion, hip arthroscopy is a useful and effective minimally invasive procedure for the diagnosis and management of selected patients with post-traumatic hip pain. Moreover, hip arthroscopy was safe technique with no reported serious adverse events.
The Nature of the Rome Statute of the International Criminal Court (and its Amended Jurisdictional Scheme)
Authors: Galand Alexandre Skander
Published: November 2019

This article shows that in the 20 years following the adoption of the Rome Statute of the International Criminal Court its nature has surfed on three waves. Building upon the Court’s case law on the principle of legality and the immunity of state officials from non-party states, it shows that the Statute was initially conceived to be of universal nature, transcending the interests of all states. However, following a series of pushbacks, the Court revised this case law to rightly acknowledge that its Statute is first of all a multilateral treaty regulating the conduct committed in the territory and by nationals of its states parties. Yet, this second wave maintained the potential for the Statute to be universally applicable when the Court’s jurisdiction is based on ad hoc declarations of acceptance or Security Council referrals. However, the journey to amend the Statute to define the crime of aggression and new war crimes might have made the prospects for universal application dependent upon universal ratification. This article argues that this third wave certainly evinces a novel shift towards state consent, but that direct and indirect forms of consent can still premise the Court’s jurisdiction over situations concerning states which have not ratified the Statute or its amendments.
Radiotherapy for local recurrence of non-small-cell lung cancer after lobectomy and lymph node dissection—can local recurrence be radically cured by radiation?
Authors: Terada Yukihiro , Isaka Mitsuhiro , Harada Hideyuki , Konno Hayato , Kojima Hideaki , Mizuno Tetsuya , Murayama Shigeyuki , Takahashi Toshiaki , Ohde Yasuhisa
Published: November 2019

Background

There is no standard therapeutic approach for local recurrence of non-small cell lung cancer (NSCLC) after complete resection. We investigated the outcomes of radiotherapy (RT) for patients with local recurrence.

Methods

We reviewed 46 patients who underwent curative-intent RT for local recurrence after lobectomy or pneumonectomy accompanied with mediastinal lymph node dissection between 2002 and 2014. We analyzed overall survival (OS), progression-free survival (PFS), local control, tumour response and the re-recurrence pattern.

Results

Among the 46 patients, 16 received concurrent chemotherapy. The median follow-up period was 48 months. The response rate was 91%. The 5-year OS and local control rates were 47.9 and 65.3%, respectively, and the 5-year PFS rate was 22.8%. Female sex and complete response to radiation were favourable prognostic factors. Of the 33 patients with recurrence after radiation, 32 (97%) had distant metastasis.

Conclusions

Although RT for local recurrence has high efficacy, distant relapse after radiation remains a major issue. Therefore, combination systemic therapy for local recurrence at any site should be further investigated. Since it is difficult to achieve a radical cure for local recurrence using RT, further study, for the administration of post-operative adjuvant therapy, is recommended.
Musth and its effects on male–male and male–female associations in Asian elephants
Authors: Keerthipriya P , Nandini S , Gautam Hansraj , Revathe T , Vidya T N C
Published: November 2019

Musth is an annual, asynchronous, rut-like phenomenon observed in male elephants. We examined whether musth is a roving strategy, and whether musth provides a temporary advantage to young males through increased access to female groups. We collected long-term data on the musth status, associations, and locations of male elephants in the Kabini population in southern India. We sighted older males more frequently in musth than younger males. We found a greater turnover of musth than non-musth males in the study area, suggesting that musth is a roving strategy, enabling males to travel widely and away from their non-musth range. Contrary to our expectation, young (15–30 years old) males spent a smaller proportion of their musth time than their non-musth time associating with females, and associated with similarly sized female groups irrespective of musth status. Old (> 30 years old) males spent only a slightly higher proportion of their musth time than non-musth time with female groups, but associated with larger female groups during musth. Although old males in musth associated with young non-musth males more often in the presence, than in the absence, of females, young males in musth were never sighted with old non-musth males in the presence of females. Therefore, the payoff from musth, as a strategy to gain access to females, was age-specific; musth in old males allowed for increased association with females, while musth in young males restricted their access to females. There was no spatial avoidance between musth and non-musth adult males at scales larger than immediate associations. Our results suggest that musth seems to be primarily a roving strategy for old males to find and associate with females and not a strategy for young males to gain a temporary advantage over old males, within the broad age-classes that we examined.
Borderline Estrogen Receptor–Positive Breast Cancers in Black and White Women
Authors: Benefield Halei C , Allott Emma H , Reeder-Hayes Katherine E , Perou Charles M , Carey Lisa A , Geradts Joseph , Sun Xuezheng , Calhoun Benjamin C , Troester Melissa A
Published: November 2019

Background

Some breast tumors expressing greater than 1% and less than 10% estrogen receptor (ER) positivity (ER-borderline) are clinically aggressive; others exhibit luminal biology. Prior ER-borderline studies included few black participants.

Methods

Using the Carolina Breast Cancer Study (phase I: 1993–1996; 2: 1996–2001; 3: 2008–2013), a population-based study that oversampled black women, we compared ER-borderline (n = 217) to ER-positive (n = 1885) and ER-negative (n = 757) tumors. PAM50 subtype and risk of recurrence score (ROR-PT, incorporates subtype, proliferation, tumor size) were measured. Relative frequency differences (RFD) were estimated using multivariable linear regression. Disease-free interval (DFI) was evaluated by ER category and endocrine therapy receipt, overall and by race, using Kaplan Meier and Cox models. Statistical tests were two-sided.

Results

ER-borderlines were more frequently basal-like (RFD = +37.7%, 95% confidence interval [CI] = 27.1% to 48.4%) and high ROR-PT (RFD = +52.4%, 95% CI = 36.8% to 68.0%) relative to ER-positives. Having a high ROR-PT ER-borderline tumor was statistically significantly associated with black race (RFD = +26.2%, 95% CI = 9.0% to 43.3%). Compared to ER-positives, DFI of ER-borderlines treated with endocrine therapy was poorer but not statistically significantly different (hazard ratio [HR] = 2.03, 95% CI = 0.89% to 4.65%), whereas DFI was statistically significantly worse for ER-borderlines without endocrine therapy (HR = 3.33, 95% CI = 1.84% to 6.02%). However, black women with ER-borderline had worse DFI compared to ER-positives, even when treated with endocrine therapy (HR = 2.77, 95% CI = 1.09% to 7.04%).

Conclusions

ER-borderline tumors were genomically heterogeneous, with survival outcomes that differed by endocrine therapy receipt and race. Black race predicted high-risk ER-borderlines and may be associated with poorer endocrine therapy response.
Pararectal angiomyxoma: a diagnostic dilemma
Authors: Dalvi Abhay N , Garale Mahadeo N , Churiwala Jayati J , Landge Avinash , Husain Sakina , Rewatkar Ajinkya
Published: November 2019

Clinical diagnosis of pararectal masses remains a challenge to this day. Despite the availability of advanced imaging facilities, we often fail to reach a definitive diagnosis and have to resort to surgery. We describe a case of a 60-year-old female with a painless perianal swelling gradually increasing in size for 6 months with spontaneous reduction on assuming a supine position. Clinical examination of this patient was suggestive of a pelvic floor hernia. However, radiological investigations were suggestive of an ischiorectal abscess. In view of lack of radiological corroboration of clinical findings, patient underwent diagnostic laparoscopy which ruled out a hernia. A wide local excision of the mass was performed, which on histopathology with immunohistochemistry examination revealed an aggressive pararectal angiomyxoma.
To furcate or not to furcate: the dance between vessel number and diameter in leaves
Authors: Rosell Julieta A , Olson Mark E
Published: November 2019

This article comments on:

Lechthaler S, Colangeli P, Gazzabin M, Anfodillo T. 2019. Axial anatomy of the leaf midrib provides new insights into the hydraulic architecture and cavitation patterns of Acer pseudoplatanus leaves. Journal of Experimental Botany 70, 6195–6202.
Viability of tDCS in Military Environments for Performance Enhancement: A Systematic Review
Authors: Feltman Kathryn A , Hayes Amanda M , Bernhardt Kyle A , Nwala Emmanuel , Kelley Amanda M
Published: November 2019

Introduction

Transcranial electrical stimulation (tES) as a method of cognitive enhancement in both diseased and healthy individuals has gained popularity. Its potential for enhancing cognition in healthy individuals has gained the interest of the military. However, before it being implemented into military training or operational settings, further work is needed to determine its efficacy and safety. Although a considerable amount of literature exists, few studies have specifically evaluated its use in enhancing cognition relative to operational, military tasks. Therefore, in a first step to evaluate its efficacy, we completed a systematic literature review of studies using transcranial direct current stimulation (tDCS), a type of tES, to enhance cognitive processes in healthy individuals.

Methods

A systematic literature review was conducted to identify literature published between 2008 and 2018 that used a method of tES for cognitive enhancement. As part of a larger literature review effort, 282 articles were initially retrieved. These were then screened to identify articles meeting predetermined criteria, to include those using various methods of tES, resulting in 44 articles. Next, the articles were screened for those using tDCS or high-definition tDCS, resulting in 34 articles for review and information extraction.

Results

Of the 34 articles reviewed, 28 reported some degree of enhancement (eg, improved accuracy on tasks and reduced reaction times). Areas of cognitive enhancements included executive functioning, creativity/cognitive flexibility, attention/perception, decision-making, memory, and working memory. However, the precise outcomes of enhancement varied given the range in tasks that were used to assess the constructs. Additionally, the stimulation parameters in terms of intensity applied, duration of stimulation, and brain region targeted for stimulation varied.

Conclusions

The conclusions to be drawn from this systematic literature review include the identification of a brain region for targeting with stimulation to enhance a broad range of cognitive constructs applicable to military tasks, as well as stimulation parameters for duration and intensity. The dorsolateral prefrontal cortex was most frequently targeted in the studies that found enhanced performance across several cognitive constructs. Stimulation intensities of 2 mA and durations of 20 minutes or longer appeared frequently as well. Although several parameters were identified, further work is required before this type of technology can be recommended for operational use.
Weight Loss Intervention Impact on the Physical Fitness Test Scores of Air Force Service Members
Authors: Pebley Kinsey , Beauvais Alexis , Gladney Leslie A , Kocak Mehmet , Klesges Robert C Klesges , Hare Marion , Richey Phyllis A , Johnson Karen C , Hryshko-Mullen Ann , Talcott G Wayne , Krukowski Rebecca A
Published: November 2019

Introduction

Overweight and obesity are a major public health concern in the United States, including among active duty military personnel. Approximately 51% of active duty personnel are classified as overweight and 15% are classified as obese. This may impact military readiness. The current study aimed to determine if a weight loss intervention impacted fitness test scores among Air Force personnel.

Materials and Methods

From 2014 to 2016, 204 Air Force members with overweight/obesity were randomized into either a Self-paced or counselor-initiated arm in a weight loss program. Study procedures were approved by the Institutional Review Board of the 59th Medical Wing in San Antonio and were acknowledged by the Institutional Review Board at the University of Tennessee Health Science Center. Fitness test scores from before, during, and after the intervention were used to determine if the intervention resulted in improvements in overall fitness test ratings and scores on individual components of the test.

Results

Participants who lost at least 5% of their weight had better fitness ratings during the intervention compared to individuals who did not lose 5%. However, in the overall sample, fitness ratings worsened from preintervention to during the intervention, and from during to postintervention. Participants with overweight had better aerobic scores pre- and postintervention as well as better abdominal circumference scores and better fitness test ratings preintervention, during the intervention and postintervention compared to participants with obesity.

Conclusions

Behavioral weight management interventions that achieve 5% weight loss may help improve military fitness test ratings.
HaloTag-based conjugation of proteins to barcoding-oligonucleotides
Authors: Yazaki Junshi , Kawashima Yusuke , Ogawa Taisaku , Kobayashi Atsuo , Okoshi Mayu , Watanabe Takashi , Yoshida Suguru , Kii Isao , Egami Shohei , Amagai Masayuki , Hosoya Takamitsu , Shiroguchi Katsuyuki , Ohara Osamu
Published: November 2019

Highly sensitive protein quantification enables the detection of a small number of protein molecules that serve as markers/triggers for various biological phenomena, such as cancer. Here, we describe the development of a highly sensitive protein quantification system called HaloTag protein barcoding. The method involves covalent linking of a target protein to a unique molecule counting oligonucleotide at a 1:1 conjugation ratio based on an azido–cycloalkyne click reaction. The sensitivity of the HaloTag-based barcoding was remarkably higher than that of a conventional luciferase assay. The HaloTag system was successfully validated by analyzing a set of protein-protein interactions, with the identification rate of 44% protein interactions between positive reference pairs reported in the literature. Desmoglein 3, the target antigen of pemphigus vulgaris, an IgG-mediated autoimmune blistering disease, was used in a HaloTag protein barcode assay to detect the anti-DSG3 antibody. The dynamic range of the assay was over 104-times wider than that of a conventional enzyme-linked immunosorbent assay (ELISA). The technology was used to detect anti-DSG3 antibody in patient samples with much higher sensitivity compared to conventional ELISA. Our detection system, with its superior sensitivity, enables earlier detection of diseases possibly allowing the initiation of care/treatment at an early disease stage.
Regioselective formation of RNA strands in the absence of magnesium ions
Authors: Motsch Sebastian , Tremmel Peter , Richert Clemens
Published: November 2019

The oligomerization of ribonucleotides can produce short RNA strands in the absence of enzymes. This reaction gives one of two regioisomeric phosphodiester linkages, a 2′,5′- or a 3′,5′-diester. The former, non-natural linkage is detrimental for duplex stability, and is known to form preferentially in oligomerizations occurring in homogeneous solution with preactivated nucleotides in the presence of magnesium cations. We have studied ribonucleotide oligomerization with in situ activation, using NMR as monitoring technique. Unexpectedly, the known preference for 2′,5′-linkages in the oligomerization of AMP was reversed in the absence of magnesium ions at slightly basic pH. Further, oligomerization was surprisingly efficient in the absence of Mg2+ salts, producing oligomers long enough for duplex formation. A quantitative systems chemistry analysis then revealed that the absence of magnesium ions favors the activation of nucleotides, and that the high concentration of active species can compensate for slower coupling. Further, organocatalytic intermediates can help to overcome the unfavorable regioselectivity of the magnesium-catalyzed reactions. Our findings allay concerns that RNA may have been difficult to form in the absence of enzymes. They also show that there is an efficient path to genetic material that does not require mineral surfaces or cations known to catalyze RNA hydrolysis.