bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defining benzodiazepine dependence: the confusion persists
Authors: Linsen SM , Zitman FG , Breteler MHM 
Published: July 2002

SummaryLittle consensus exists on the risk of benzodiazepine (BZD) dependence. We investigated how often BZD dependence and related concepts have been defined in the literature on BZD effects in humans. In addition, the definitions of BZD dependence were compared in order to assess the similarity of contents. From a total of 250 papers (published between 1988 and 1991) 51 provided 126 dependence-related definitions. Six studies referred to the DSM definitions and one to the WHO definition. The obsolete concept of addiction was frequently defined (n=13), with little consensus about its meaning. Psychological and physical dependence were defined fairly often (n=29), also with low levels of consensus. We conclude that the discussion on the risk of BZD dependence would be well-served by attempting to improve consensus first. This may lead to more meaningful data on the incidence, prevalence and relevant co-factors of BZD dependence. An outline for criteria for benzodiazepine dependence is presented.
The naloxone conjunctival test: an underused tool? A review of the available data
Authors: Auriacombe M , Cornish JW , Skoble L , O’Brien CP 
Published: July 2002

SummaryThere is currently no simple and morbidity-free procedure available to determine opiate dependence in patients. There is preliminary evidence, however, that the naloxone conjunctival test may be useful in this regard. This test consists of instilling a drop of saline solution of naloxone hydrochloride (an opiate-receptor antagonist) into the subject's eye. This causes significant homolateral mydriasis (anisocoria) in the eye of a chronic opioid-dependent subject and not in that of a non-dependent subject. We reviewed the international literature on the naloxone conjunctival test using the Medline database and a manual search of major scientific journals specialized in the field of substance abuse. Up to March 1995, we identified six articles dealing specifically with the use of opiate antagonist ophthalmic solutions in populations of chronic opioid addicts. Four of the articles reported the occurrence of mydriasis when a solution of naloxone is used in opioid addicts. Two of the articles reported that there was no differential change in pupil size when the naloxone solution is used; however, one study used a much weaker and the other a much stronger solution of naloxone than reported in the other studies. From our review of the literature, it appears that the naloxone conjunctival test holds great promise as a simple and morbidity-free method of testing for chronic opioid addiction and, therefore, it should be studied further and its usage eventually developed.
Cortisol-binding globulin levels in bipolar disorder
Authors: Vieta E , Gastó C , de Osaba MJ Martínez , Otero A , Nieto E , Pintor L , Blanch J , Vallejo J 
Published: July 2002

SummaryCortisol-binding globulin (CBG) is an alpha-1-glycoprotein with high affinity for cortiso that could be a potential biological marker of chronic stress, according to several previous studies. In order to examine CBG concentrations in bipolar disorder, we determined serum CBG levels by radioimmunoassay with monoclonal antibodies in a sample of 39 RDC bipolar I patients in remission and 21 healthy age-, sex- and weight-matched control subjects. Only lithium treatment was permitted. Plasma cortisol and serum lithium levels were also determined. Bipolar males showed statistically significant lower serum CBG levels than controls, whereas women showed very similar values. No correlation was found between CBG levels and cortisol or lithium concentrations. It is concluded that CBG levels are affected by chronic affective illness, even during remission periods, at least in bipolar males.
Clinical trials update: OPTIME‐CHF, PRAISE‐2, ALL‐HAT
Authors: Thackray Simon , Witte Klaus , Clark Andrew L. , Cleland John G.F. 
Published: July 2002

AbstractThis is a summary of reports of presentation made at the American College of Cardiology 49th Scientific Sessions, Anaheim, 12–15 March 2000. Studies with a particular interest for heart failure physicians have been reviewed. OPTIME‐CHF: Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure. OPTIME‐CHF was a randomised‐controlled trial comparing a 48‐h infusion of Milrinone or standard therapy in 951 patients recruited over a 2‐year period. Patients were excluded if the investigator believed their clinical condition mandated inotropic therapy. Patients were randomised within 48 h of admission for an acute exacerbation of chronic heart failure to receive Milrinone or placebo infision for 48 h. Of the patients 43% were diabetics, 70% were receiving an angiotensin converting enzyme inhibitor, 25% were already on a beta‐Blocker, and 34% had atrial fibrillation. There was no significant difference between the two groups in length of hospital stay during the index admission, subsequent readmissions and days in hospital over the following 60 days. Subjective clinical assessment scores were also no different. There was an average admission rate over the next year of one per patient in both groups. However, there was a significant increase in the incidence of sustained hypotension in the Milrinone group, which accounted for all of the increased adverse event rates for the active therapy. The 60‐day mortality was 10% in both groups. This and previous trials of the oral formulation of Milrinone have now clearly demonstrated a lack of benefit with Milrinone in either during acute exacerbations of or in stable severe chronic heart failure [Packer M, Carver JR, Rodeheffer RJ et al. Effect of oral Milrinone on mortality in severe chronic heart failure. N Engl J Med 1991;325:1468–1475.]. Medium sized studies of Milrinone in patients with milder severities of heart failure also suggested an adverse impact on prognosis in the presence or absence of digoxin [DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral Milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N Engl J Med 1989;320:677–683.]. Whether Milrinone even has a role for the management of a haemodyamic crisis requiring inotropic therapy must also be questioned.
Evolutionary Implications of Habitat Choice
Authors: Porter Cody K , Akcali Christopher K 
Published: August 2020

Abstract

There is a growing realisation that habitat choice can have profound consequences for the processes of adaptation and speciation. Habitat choice may be a rapid and effective route by which individual and population fitness are increased, potentially playing a major role in adaptive evolution that has historically been solely attributed to natural selection. Recent research indicates that there may be complex interactions between habitat selection and other processes (i.e. natural selection, phenotypic plasticity) during adaptive evolution. Likewise, the use of alternative habitats by diverging lineages appears to be a major barrier to gene flow in nature, suggesting that habitat choice also plays a major role in the diversification of life. Although the available evidence is tantalising, much remains to be known about the true extent of habitat choice's role in the evolutionary process and the mechanisms underlying its evolutionary consequences.

Key Concepts

Habitat choice can be a cause (and a consequence) of adaptation.

Habitat choice may reduce or increase the scope for other processes to contribute to adaptation.

Habitat isolation is often a strong barrier to gene flow between diverging lineages.

Habitat isolation evolves early in the process of divergence.

Habitat isolation may have been a key contributor to the extraordinary diversity of herbivorous insects.

The specific mechanisms underlying individual dispersal and settlement decisions can greatly affect the evolutionary consequences of habitat choice.
Circadian Rhythms inNeurospora
Authors: Hurley Jennifer M 
Published: August 2020

AbstractCircadian rhythms are highly conserved, 24‐h physiological cycles that, through the ideal programming of behaviour, enhance fitness by ensuring many organismal functions are optimally synchronised with the appropriate phase of the day. Circadian rhythms are controlled via an intracellular, highly regulated, transcription‐translation based negative feedback loop, or ‘clock’, and this feedback loop directly or indirectly impacts a large portion of the genome. Over half a century, genetic and molecular analysis of the circadian system ofNeurospora crassahas uncovered a number of paradigms now seen to be universal in the operation of circadian rhythms. This article summarises what is currently understood about the mechanisms that underly circadian regulation inNeurosporaand highlights many of the contributionsNeurosporahas made to understanding these same mechanisms in higher eukaryotes.Neurospora crassais a key model system for eukaryotic clocks.TheNeurosporaclock comprises a transcription‐translation negative feedback loop.Intrinsic protein disorder is essential for clock function inNeurospora.TheNeurosporaclock extensively regulates physiological output.Circadian output is regulated at the transcriptional as well as posttranscriptional levels.TheNeurosporaclock is resistant to environmental effects while remaining sensitive to environmental cues.Light, temperature and metabolic conditions are all environmental cues that can impact the oscillations of the circadian system.
Biology of Green Sulfur Bacteria
Authors: Imhoff Johannes F 
Published: August 2020

AbstractGreen sulfur bacteria, the Chlorobiaceae, have gained much attention because of unique structures of the photosynthetic apparatus and the presence of chlorosomes as very powerful light antenna that can capture minute amounts of light. This has important ecological consequences, because the efficient light‐harvesting determines the ecological niche of these bacteria at the lowermost part of stratified environments where the least of light is available. The oxidation of sulfide as their outmost important photosynthetic electron donor involves the deposition of elemental sulfur globules outside the cells and separates the process of sulfide oxidation to sulfate into two parts. This is the basis for stable syntrophic associations between green sulfur bacteria and sulfur‐ and sulfate‐reducing bacteria in which the sulfur compounds are recycled. The green sulfur bacteria are distantly related to other bacteria and systematically members of the Chlorobiaceae family withChlorobium,Chlorobaculum,ProsthecochlorisandChloroherpetonas representative genera.Green sulfur bacteria depend on light for life due to their obligate phototrophic metabolism.Green sulfur bacteria are most efficient in photosynthesis due to the presence of light‐harvesting organelles, the chlorosomes, which are filled with bacteriochlorophyll molecules.Green sulfur bacteria are offsprings of one of the most ancient bacterial lineages performing biosynthesis of bacteriochlorophyll and photosynthesis.Green sulfur bacteria inhabit the lowermost light‐receiving part of the chemocline in the stratified environment due to their high sensitivity to oxygen, high tolerance to the toxic sulfide and highly efficient light capture.Green sulfur bacteria are important drivers of oxidation of reduced sulfur compounds in the stratified, sulfide‐containing environment receiving low irradiation.
mRNA Stability
Authors: Kaberdin Vladimir 
Published: August 2020

AbstractThe steady‐state level of a messenger ribonucleic acid (mRNA) is determined by both its rate of synthesis and degradation. The degradation of mRNA is an important tool employed by cells to control gene expression and to adjust the level of protein synthesis in response to physiological needs or environmental signals. The degradation of mRNA in all organisms is mastered by a rather restricted number of enzymes with major (endo‐ and exoribonucleases) and ancillary (e.g. RNA helicases) functions. Some of these enzymes are phylogenetically conserved across the three domains of life – bacteria, archaea and eukarya. Moreover, the main components of the RNA decay machinery can associate with each other to form multienzyme complexes, which makes it possible to coordinate and control mRNA decayin vivo.The stability of individual mRNAs varies and is dependent on intrinsic properties of transcripts (i.e. specific structure and sequence) and action oftrans‐encoded regulatory factors.The enzymes and ancillary factors involved in mRNA decay in pro‐ and eukaryotic organisms can associate with each other to form multienzyme complexes such as degradosomes or exosomes.Mechanisms of mRNA decay in pro‐ and eukaryotes share many common steps.Pro‐ and eukaryotic cells use specific mechanisms to eliminate defective mRNAs.Numerous noncoding RNAs control mRNA decay in pro‐ and eukaryotes.
Eukaryotic Recombination: Initiation by Double‐Strand Breaks
Authors: Lalwani Kiran , Goodenow Donna , Richardson Christine 
Published: August 2020

Abstract

A double‐strand break (DSB) in one deoxyribonucleic acid (DNA) double helix, caused by DNA damaging agents such as ionising radiation or normal metabolic processes, can stimulate repair through multiple pathways. Homologous recombination (HR) utilises a second unbroken DNA double helix containing homologous sequences as a donor of genetic information to restore the intact DNA structure, while nonhomologous end joining (NHEJ) relegates broken DNA ends together with little to no homology. Deficiency in these repair pathways can cause genome instability can drive carcinogenesis. DSB stimulated repair can cause illegitimate HR between heterologous chromosome of the ligation of ends of DNA from heterologous chromosomes.

Exogenous and endogenous agents can cause deoxyribonucleic acid (DNA) breaks leading to genome instability.

Repair of double‐strand breaks (DSB) in eukaryotes occurs by either homology‐dependent or homology‐independent mechanisms.

Homologous recombination (HR) facilitates high‐fidelity repair of DSBs and other plausible DNA damage.

Site‐specific DSBs within the genome are used to study the explicit mechanism involved in the DSB repair.

Unlike other model organisms, HR in higher eukaryotes requires additional protein factors.

Mutations in HR proteins can increase predisposition to cancer.
Nematomorpha (Horsehair Worms)
Authors: Poinar George 
Published: August 2020

Abstract

The worldwide phylum Nematomorpha, that parasitise aquatic and terrestrial invertebrates, is a relict group unrelated to any other living or extinct phylum. One genus,
Nectonema
, is marine, while the remaining genera occur in freshwater or inside terrestrial hosts. Hairworms have two or more hosts in their life cycle. Upon hatching, the microscopic free‐living larvae are passively ingested by and encyst inside paratenic invertebrate hosts without further development. When the paratenic host is eaten by a larger invertebrate, it leaves its cyst and enters the body cavity of the new host where it may grow to an adult. If the second host is not suitable for development, the hairworm larva can encyst again and wait to be ingested by a final host. There is no direct economic or medical importance of hairworms and the long, slender adults are rarely noticed except when emerging from their final host.

Hairworms (Nematomorpha) are a unique group of invertebrate parasites.

Hairworm adults are free‐living and occur in fresh or saltwater.

After hatching, the microscopic larvae enter and encyst in invertebrates and vertebrates.

Final development occurs in large invertebrates that consume the paratenic hosts.

Most final hosts are killed when the hairworms emerge.

Hairworms are an ancient group, with fossils dating back to the mid‐Cretaceous.
Serum levels of cell adhesion molecules in patients with neuromyelitis optica spectrum disorder
Authors: Chang Bao‐Luen , Ro Long‐Sun , Chen Chiung‐Mei , Lo Yen‐Shi , Lyu Rong‐Kuo , Kuo Hung‐Chou , Liao Ming‐Feng , Chang Chun‐Wei , Chang Hong‐Shiu , Huang Ching‐Chang , Wu Yih‐Ru , Chu Chun‐Che , Weng Yi‐Ching , Chang Kuo‐Hsuan 
Published: August 2020

AbstractObjectivesBlood–brain barrier (BBB) disruption is a critical pathological process involved in neuromyelitis optica spectrum disorder (NMOSD). Here, we characterized the profile of five cell adhesion molecules in patients with NMOSD.MethodsWe measured levels of cell adhesion molecules, including ICAM‐1, ICAM‐2, VCAM‐1, PECAM‐1, and NCAM‐1, in the serum of 28 patients with NMOSD, 24 patients with multiple sclerosis (MS), and 25 healthy controls (HCs).ResultsICAM‐2 levels (median: 394.8 ng/mL) were increased in patients with NMOSD compared with MS (267.1 ng/mL, P = 0.005) and HCs (257.4 ng/mL, P = 0.007), and VCAM‐1 and ICAM‐1 levels were higher in patients with NMOSD (641.9 ng/mL and 212.7 ng/mL, respectively) compared with HCs (465 ng/mL [P = 0.013] and 141.8 ng/mL [P = 0.002], respectively). However, serum PECAM‐1 levels were lower in patients with NMOSD (89.62 ng/mL) compared with MS (106.9 ng/mL, P = 0.015) and HCs (107.2 ng/mL, P = 0.007). Receiver operating characteristic curve analysis revealed that PECAM‐1 (area under the curve (AUC): 0.729) and ICAM‐2 (AUC: 0.747) had adequate abilities to distinguish NMOSD from MS, and VCAM‐1 (AUC: 0.719), PECAM‐1 (area under the curve: 0.743), ICAM‐1 (AUC: 0.778), and ICAM‐2 (AUC: 0.749) exhibited potential to differentiate NMOSD and HCs. Serum levels of PECAM‐1 also demonstrated a negative correlation with Kurtzke Expanded Disability Status Scale scores in patients with NMOSD.InterpretationOur results reveal possible BBB breakdown signals specifically observed in NMOSD and highlight the potential role of cell adhesion molecules as biomarkers of this disease.
Altered coupling between resting‐state glucose metabolism and functional activity in epilepsy
Authors: Wang Jingjuan , Shan Yi , Dai Jindong , Cui Bixiao , Shang Kun , Yang Hongwei , Chen Zhongwei , Shan Baoci , Zhao Guoguang , Lu Jie 
Published: August 2020

AbstractObjectiveAltered functional activities and hypometabolism have been found in medial temporal lobe epilepsy patients with hippocampal sclerosis (mTLE‐HS). Hybrid PET/MR scanners provide opportunities to explore the relationship between resting‐state energy consumption and functional activities, but whether repeated seizures disturb the bioenergetic coupling and its relationship with seizure outcomes remain unknown.Methods18F‐FDG PET and resting‐state functional MRI (rs‐fMRI) scans were performed with hybrid PET/MR in 26 patients with mTLE‐HS and in healthy controls. Energy consumption was quantified by 18F‐FDG standardized uptake value ratio(SUVR) relative to cerebellum. Spontaneous neural activities were estimated using regional homogeneity (ReHo), fractional amplitude of low frequency fluctuations (fALFF) from rs‐fMRI. Between‐group differences in SUVR and rs‐fMRI derived metrics were evaluated by two‐sample t test. Voxel‐wise spatial correlations were explored between SUVR and ReHo, fALFF across gray matter and compared between groups. Furthermore, the relationships between altered fALFF/SUVR and ReHo/SUVR coupling and surgical outcomes were evaluated.ResultsBoth the patients and healthy controls showed significant positive correlations between SUVR and rs‐fMRI metrics. Spatial correlations between SUVR and fMRI‐derived metrics across gray matter were significantly higher in patients with mTLE‐HS compared with healthy controls (fALFF/SUVR, P < 0.001; ReHo/SUVR, P = 0.022). Higher fALFF/SUVR couplings were found in patients who had Engel class IA after surgery than all other (P = 0.025), while altered ReHo/SUVR couplings (P = 0.097) were not.ConclusionThese findings demonstrated altered bioenergetic coupling across gray matter and its relationship with seizure outcomes, which may provide novel insights into pathogenesis of mTLE‐HS and potential biomarkers for epilepsy surgery planning.
Novel CAPN1 mutations extend the phenotypic heterogeneity in combined spastic paraplegia and ataxia
Authors: Lai Lu‐Lu , Chen Yi‐Jun , Li Yun‐Lu , Lin Xiao‐Hong , Wang Meng‐Wen , Dong En‐Lin , Wang Ning , Chen Wan‐Jin , Lin Xiang 
Published: August 2020

AbstractObjectiveRecessive mutations in the CAPN1 gene have recently been identified in spastic paraplegia 76 (SPG76), a complex hereditary spastic paraplegia (HSP) that is combined with cerebellar ataxia, resulting in an ataxia‐spasticity disease spectrum. This study aims to assess the influence of CAPN1 variants on the occurrence of SPG76 and identify factors potentially contributing to phenotypic heterogeneity.MethodsWe screened a cohort of 240 unrelated HSP families for variants in CAPN1 using high‐throughput sequencing analysis. We described in detail the clinical and genetic features of the SPG76 patients in our cohort and summarized all reported cases.ResultsSix unreported CAPN1‐associated families containing eight patients with or without cerebellar ataxia were found in our cohort of HSP cases. These patients carried three previously reported homozygous truncating mutations (p.V64Gfs*103, c.759+1G>A, and p.R285*), and three additional novel compound heterozygous missense mutations (p.R481Q, p.P498L, and p.R618W). Lower limbs spasticity, hyperreflexia, and Babinski signs developed in about 94% of patients, with ataxia developing in 63% of cases. In total, 33 pathogenic mutations were distributed along the three reported functional domains of calpain‐1 protein, encoded by CAPN1, with no hotspot region. A comparison of gender distribution between the two groups indicated that female SPG76 patients were significantly more likely to present with complicated HSP than male patients (P = 0.015).InterpretationOur study supports the clinically heterogeneous inter‐ and intra‐family variability of SPG76 patients, and demonstrates that gender and calpain‐1 linker structure may contribute to clinical heterogeneity in SPG76 cases.
Centromedian thalamic responsive neurostimulation for Lennox‐Gastaut epilepsy and autism
Authors: Kwon Churl‐Su , Schupper Alexander J. , Fields Madeline C. , Marcuse Lara V. , La Vega‐Talbott Maite , Panov Fedor , Ghatan Saadi 
Published: August 2020

AbstractThe RNS System is not approved in patients under 18, although a critical need for novel treatment modalities in this vulnerable population persist. We present two pediatric patients with drug‐resistant epilepsy secondary to Lennox‐Gastaut Syndrome (LGS) and autism spectrum disorder (ASD) treated with the RNS System. Both patients have experienced 75–99% clinical seizure reductions in >1 year of follow‐up. We illustrate that children with diffuse onset, multifocal epilepsy, including frontal and thalamic circuits thought to exist in the generation of LGS seizures, can be treated with responsive neurostimulation safely and effectively, targeting thalamic networks, and avoiding palliative disconnections and resections.
Synthesis of Pyridothiazepines via a 1,5‐Dipolar Cycloaddition Reaction between Pyridinium 1,4‐Zwitterionic Thiolates and Activated Allenes
Authors: Cheng Bin , Zhang Xinping , Li Hui , He Yixuan , Li Yun , Sun Haiyan , Wang Taimin , Zhai Hongbin 
Published: August 2020

AbstractThe synthesis of pyridothiazepines has been achieved via a 1,5‐dipolar cycloaddition reaction between pyridinium 1,4‐zwitterionic thiolates and activated allenes conducted under thermal conditions. Meanwhile, a ring‐contraction reaction of the resulting pyridothiazepine derivatives via the extrusion of 3‐thioxoacrylates has also been described.magnified image