gebhart/patrepeval huggingface dataset:
Mixed‐effects models and the drug titration paradox (2023)

We read with interest the article of Kristensen et al.1 about overcoming the titration paradox. Their study highlighted how the pooled titration data from all individuals when graphed may indicate the wrong direction of the slope for the dose–response curve and, as we also illustrated,2 would show a flat dose–response when based on end-of-trial data. They demonstrate by means of simulation that the titration paradox may be overcome if longitudinal data from dose titration trials is analyzed using a population approach that accounts for interindividual variability and there is a clear causal relationship between the response and the dose at every timepoint. We appreciate the authors’ interest in this topic. We agree that in some situations a mixed effects model will be helpful in the analysis of data from titration studies. However, we recently showed that a linear mixed-effects model did not identify the correct underlying dose–response relationship in titration data during clinical anesthesia, because of the presence of the titration paradox in the individual data.3 Clearly, when the individual data show a titration paradox, a mixed-effects model, which only accounts for interindividual variability, will still not reveal the correct underlying pharmacology. As highlighted by Kristensen et al., the causal relationship must be clear. If the causal relationship between the measured effect and the titrated dose is confounded by other explanatory variables that were not available to be included in the analysis, a mixed effects model will not overcome the titration paradox. In our data, we believe that these explanatory variables were most likely the changing levels of surgical stimulus, blood loss, and other unmeasured confounders. We all agree that with classical dosing the measured effect is a function of the dose administered (i.e., the dose is the independent variable and the response the dependent variable). However, when the dose is titrated according to the measured effect, we believe that the response becomes the independent variable, and the titrated dose becomes the dependent variable. We would encourage authors to consider switching x–y axes of the dose–response curves to reflect this causal relationship when titration data are graphically displayed. No funding was received for this work. The authors declared no competing interests for this work.
Telematics will be useful in providing information (1996)

on which over the counter drug they had recom- mended and the reason for the recommendation.Table 1 gives the number and proportion of consultations at which information on prior use of an over the counter drug was elicited and at which a prescription was issued or an over the counter drug was recommended, or both.Over the counter drugs were recommended during 444 consultations, but the actual drug was stated in only 413.The six general practitioners varied considerably in their rates of recommending over the counter drugs (from 2.3% to 37.5%) and issuing prescriptions (from 30.6% to 78.2%).Recommending an over the counter drug seems to be a management option that is used in addition to, rather than instead of, issuing a prescription.Most recommendations (305/413) were for simple analgesics, especially paracetamol preparations (184/413).Medicines that have changed since 1990 from being available only on prescription to being available in pharmacies hardly featured (8/413).The main reason doctors gave for recommending over the counter drugs was that they were cheaper for some patients.Increasing patient autonomy or capacity for self care and potential savings in the practice's prescribing budget did not emerge as major reasons for recommending over the counter drugs.
BEET NECROTIC YELLOW VEIN VIRUS AND BEET SOILBORNE MOSAIC VIRUS: A PRELIMINARY STUDY OF RNAs REASSORTMENT (2014)

Beet necrotic yellow vein virus (BNYVV) and Beet soil-borne mosaic virus (BSBMV) (Benyviridae family) are distinct but closely related species possessing the same host range, vector and multipartite genome of four to five ssRNAs (+) that represent an interesting model to study plant-virus interactions. RNA-1 and -2 combination (helper strain) is essential for the infection and the replication of both viruses, while RNA-3 and -4 are accessory RNAs playing important roles in plant-virus and virusvector interactions, respectively. Previous work demonstrated on the one hand the ability of BNYVV/BSBMV helper strains to handle the replication and packaging of cognate small RNA segments, on the other hand, the availability of a functional exchange of genomic RNA-1 between both viral species. nterestingly, one of the two chimeric combinations induced a strong necrosis of the infected Chenopodium quinoa leading to a dead end for the recombinant virus. Such dramatic cell death or incompatible reaction could explain why no natural chimeras have ever been found in plant naturally infected with both viruses. As both viruses could co-exist in the same plant, a mixture of both genomic RNAs in the same cell should be avoided, particularly when the virus moves at a long distance. The unavailability of benyviridaes genomic RNA reassortment, in particular for RNA-1, has been tested in C. quinoa and Nicotiana benthamiana local and systemic host, respectively, using BNYVV/BSBMV full-length infectious cDNA clones and agroclones in a genetic reverse approach.
ChemInform Abstract: Diels—Alder Cycloaddition in Medicinal Chemistry (2016)

ChemInformVolume 47, Issue 49 Reviews ChemInform Abstract: Diels—Alder Cycloaddition in Medicinal Chemistry Laure C. Bouchez, Laure C. Bouchez Novartis Inst. Biomed. Res., Novartis Pharma AG, CH-4056 Basel, Switz.Search for more papers by this authorMarion Rusch, Marion Rusch Novartis Inst. Biomed. Res., Novartis Pharma AG, CH-4056 Basel, Switz.Search for more papers by this authorMarie-Helene Larraufie, Marie-Helene Larraufie Novartis Inst. Biomed. Res., Novartis Pharma AG, CH-4056 Basel, Switz.Search for more papers by this author Laure C. Bouchez, Laure C. Bouchez Novartis Inst. Biomed. Res., Novartis Pharma AG, CH-4056 Basel, Switz.Search for more papers by this authorMarion Rusch, Marion Rusch Novartis Inst. Biomed. Res., Novartis Pharma AG, CH-4056 Basel, Switz.Search for more papers by this authorMarie-Helene Larraufie, Marie-Helene Larraufie Novartis Inst. Biomed. Res., Novartis Pharma AG, CH-4056 Basel, Switz.Search for more papers by this author First published: 17 November 2016 https://doi.org/10.1002/chin.201649211AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume47, Issue49November, 2016 RelatedInformation
Everything Matters: The ReproNim Perspective on Reproducible Neuroimaging (2019)

There has been a recent major upsurge in the concerns about reproducibility in many areas of science. Within the neuroimaging domain, one approach is to promote reproducibility is to target the re-executability of the publication. The information supporting such re-executability can enable the detailed examination of how an initial finding generalizes across changes in the processing approach, and sampled population, in a controlled scientific fashion. ReproNim: A Center for Reproducible Neuroimaging Computation is a recently funded initiative that seeks to facilitate the "last mile" implementations of core re-executability tools in order to reduce the accessibility barrier and increase adoption of standards and best practices at the neuroimaging research laboratory level. In this report, we summarize the overall approach and tools we have developed in this domain.
Fringe Dielectrophoresis Nanoaperture Optical Trapping with Order of Magnitude Speed-Up for Unmodified Proteins (2023)

Single molecule analysis of proteins in an aqueous environment without modification (e.g., labels or tethers) elucidates their biophysics and interactions relevant to drug discovery. By combining fringe-field dielectrophoresis with nanoaperture optical tweezers we demonstrate an order of magnitude faster time-to-trap for proteins when the counter electrode is outside of the solution. When the counter electrode is inside the solution (the more common configuration found in the literature), electrophoresis speeds up the trapping of polystyrene nanospheres, but this was not effective for proteins in general. Since time-to-trap is critical for high-thoughput analysis, these findings are a major advancement to the nanoaperture optical trapping technique for protein analysis.
Confocal endomicroscopy: a novel maging technique forin vivohistology of cervical intraepithelial neoplasia (2007)

Optical imaging technologies, such as reflectance and fluorescence spectroscopy, have shown the potential to provide enhanced detection of changes in the uterine cervix at clinical examination. This review focuses on fluorescence confocal endomicroscopy that enables in vivo microscopic imaging of the cervical epithelium in histological detail in real time. The microscopic imaging technique may permit 'see-and-treat' workflows in colposcopy through high-resolution fluorescence imaging of cellular and subcellular detail from the surface and subepithelial layers of the cervical mucosa. The device may be used in conjunction with a conventional colposcope. Preliminary data from clinical studies suggest that the device can be used to visualize features of the cervical epithelium including the squamo-columnar junction, dermal papillae and endocervical glands. Moreover, the technique has the ability to detect and grade precancerous changes of the cervical epithelium in conditions, such as cervical intraepithelial neoplasia, where prediction using colposcopy may be problematic. The early detection and diagnosis of gynecological abnormalities through the collection of 'optical' biopsies or targeted mucosal excisional biopsies have the potential to improve patient management through early therapeutic intervention and 'see-and-treat' strategies.
Extended-Spectrum β-Lactamases in Klebsiella pneumoniae Bloodstream Isolates from Seven Countries: Dominance and Widespread Prevalence of SHV- and CTX-M-Type β-Lactamases (2003)

A huge variety of extended-spectrum beta-lactamases (ESBLs) have been detected during the last 20 years. The majority of these have been of the TEM or SHV lineage. We have assessed ESBLs occurring among a collection of 455 bloodstream isolates of Klebsiella pneumoniae, collected from 12 hospitals in seven countries. Multiple beta-lactamases were produced by isolates with phenotypic evidence of ESBL production (mean of 2.7 beta-lactamases per isolate; range, 1 to 5). SHV-type ESBLs were the most common ESBL, occurring in 67.1% (49 of 73) of isolates with phenotypic evidence of ESBL production. In contrast, TEM-type ESBLs (TEM-10 type, -12 type, -26 type, and -63 type) were found in just 16.4% (12 of 73) of isolates. The finding of TEM-10 type and TEM-12 type represents the first detection of a TEM-type ESBL in South America. PER (for Pseudomonas extended resistance)-type beta-lactamases were detected in five of the nine isolates from Turkey and were found with SHV-2-type and SHV-5-type ESBLs in two of the isolates. CTX-M-type ESBLs (bla(CTX-M-2) type and bla(CTX-M-3) type) were found in 23.3% (17 of 73) of isolates and were found in all study countries except for the United States. We also detected CTX-M-type ESBLs in four countries where they have previously not been described-Australia, Belgium, Turkey, and South Africa. The widespread emergence and proliferation of CTX-M-type ESBLs is particularly noteworthy and may have important implications for clinical microbiology laboratories and for physicians treating patients with serious K. pneumoniae infections.
Point Spread Function (PSF) noise filter strategy for geiger mode LiDAR (2013)

LiDAR is an efficient optical remote sensing technology that has application in geography, forestry, and defense. The effectiveness is often limited by signal-to-noise ratio (SNR). Geiger mode avalanche photodiode (APD) detectors are able to operate above critical voltage, and a single photoelectron can initiate the current surge, making the device very sensitive. These advantages come at the expense of requiring computationally intensive noise filtering techniques. Noise is a problem which affects the imaging system and reduces the capability. Common noise-reduction algorithms have drawbacks such as over aggressive filtering, or decimating in order to improve quality and performance. In recent years, there has been growing interest on GPUs (Graphics Processing Units) for their ability to perform powerful massive parallel processing. In this paper, we leverage this capability to reduce the processing latency. The Point Spread Function (PSF) filter algorithm is a local spatial measure that has been GPGPU accelerated. The idea is to use a kernel density estimation technique for point clustering. We associate a local likelihood measure with every point of the input data capturing the probability that a 3D point is true target-return photons or noise (background photons, dark-current). This process suppresses noise and allows for detection of outliers. We apply this approach to the LiDAR noise filtering problem for which we have recognized a speed-up factor of 30-50 times compared to traditional sequential CPU implementation.
Estimating the nutritive value of cereal crop residues: Implications for developing feeding standards for draught animals (1989)

Reviews analytical methods for the determination of the nutritive value of crop residues. Gives example on the accuracy of different methods in determining digestibility and of the factors affecting it. Highlights different management practices for feeding cereal crop residues to draught animals.
Structure and function of an N‐acetyltransferase from the human pathogen Acinetobacter baumannii isolate BAL_212 (2022)

Acinetobacter baumannii is a Gram-negative bacterium commonly found in soil and water that can cause human infections of the blood, lungs, and urinary tract. Of particular concern is its prevalence in health-care settings where it can survive on surfaces and shared equipment for extended periods of time. The capsular polysaccharide surrounding the organism is known to be the major contributor to virulence. The structure of the K57 capsular polysaccharide produced by A. baumannii isolate BAL_212 from Vietnam was recently shown to contain the rare sugar 4-acetamido-4,6-dideoxy-d-glucose. Three enzymes are required for its biosynthesis, one of which is encoded by the gene H6W49_RS17300 and referred to as VioB, a putative N-acetyltransferase. Here, we describe a combined structural and functional analysis of VioB. Kinetic analyses show that the enzyme does, indeed, function on dTDP-4-amino-4,6-dideoxy-d-glucose with a catalytic efficiency of 3.9 x 10<sup>4</sup> M<sup>-1</sup> s<sup>-1</sup> (±6000), albeit at a reduced value compared to similar enzymes. Three high-resolution X-ray structures of various enzyme/ligand complexes were determined to resolutions of 1.65 Å or better. One of these models represents an intermediate analogue of the tetrahedral transition state. Differences between the VioB structure and those determined for the N-acetyltransferases from Campylobacter jejuni (PglD), Caulobacter crescentus (PerB), and Psychrobacter cryohalolentis (Pcryo_0637) are highlighted. Taken together, this investigation sheds new insight into the Type I sugar N-acetyltransferases.
Identification of a new heterozygous point mutation in the COL1A2 gene leading to skipping of exon 9 in a patient with joint laxity, hyperextensibility of skin and blue sclerae (1998)

A heterozygous deletion of exon 9 in the COL1A2 - mRNA of a patient with symptoms of both the Ehlers - Danlos - Syndrome and the Osteogenesis Imperfecta is described. In the genomic DNA of the patient, exon 9 is homozygously present. We identified a novel heterozygous point mutation in the splice donor site of intron 9, leading to a G→A substitution in position +5. This mutation leads to heterozygous skipping of exon 9 in the COL1A2 - mRNA of this patient. The deletion results in a shortened (by 18 amino acids) but in frame l2(1) chain, which probably leads to the formation of abberantly processed triple helices. Hum Mutat 12:138, 1998. © 1998 Wiley-Liss, Inc.
ChemInform Abstract: A Mild and Selective Method for N‐Boc Deprotection. (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
[Preventive effect of captopril on the development of genetic hypertension in SHR rats (author's transl)]. (1981)

Captopril, an inhibitor of the angiotensin-converting enzyme, is very effective in preventing the development of genetic hypertension in SHR rats. This effect results from early, overall lowering of local vascular resistances and, consequently, suppression of the age-related increase in total peripheral resistance. Contrary to that of dihydralazine and atenolol, it persists for up to 12 weeks after the drug is discontinued. Captopril may act by inhibiting the angiotensin-converting enzyme present in the vascular wall, with subsequent temporary arrest of the vascular lesions associated with progressive genetic hypertension.
Differential Reward Coding in the Subdivisions of the Primate Caudate during an Oculomotor Task (2012)

The basal ganglia play a pivotal role in reward-oriented behavior. The striatum, an input channel of the basal ganglia, is composed of subdivisions that are topographically connected with different cortical and subcortical areas. To test whether reward information is differentially processed in the different parts of the striatum, we compared reward-related neuronal activity along the dorsolateral-ventromedial axis in the caudate nucleus of monkeys performing an asymmetrically rewarded oculomotor task. In a given block, a target in one position was associated with a large reward, whereas the other target was associated with a small reward. The target position-reward value contingency was switched between blocks. We found the following: (1) activity that reflected the block-wise reward contingency emerged before the appearance of a visual target, and it was more prevalent in the dorsal, rather than central and ventral, caudate; (2) activity that was positively related to the reward size of the current trial was evident, especially after reward delivery, and it was more prevalent in the ventral and central, rather than dorsal, caudate; and (3) activity that was modulated by the memory of the outcomes of the previous trials was evident in the dorsal and central caudate. This multiple reward information, together with the target-direction information, was represented primarily by individual caudate neurons, and the different reward information was represented in caudate subpopulations with distinct electrophysiological properties, e.g., baseline firing and spike width. These results suggest parallel processing of different reward information by the basal ganglia subdivisions defined by extrinsic connections and intrinsic properties.
Proliferative Vitreoretinopathy: A Review (2018)

Proliferative vitreoretinopathy (PVR) is the most common cause for failure of rhegmatogenous retinal detachment repair and is characterized by the growth and contraction of cellular membranes within the vitreous cavity and on both sides of the retinal surface as well as intraretinal fibrosis. Currently, PVR is thought to be an abnormal wound healing response that is primarily driven by inflammatory, retinal, and RPE cells. At this time, surgery is the only management option for PVR as there is no proven pharmacologic agent for the treatment or prevention of PVR. Laboratory research to better understand PVR pathophysiology and clinical trials of various agents to prevent PVR formation are ongoing.
Wireless Modification of the Intraoperative Examination Monitor for Awake Surgery -Technical Note- (2011)

The dedicated intraoperative examination monitor for awake surgery (IEMAS) was originally developed by us to facilitate the process of brain mapping during awake craniotomy and successfully used in 186 neurosurgical procedures. This information-sharing device provides the opportunity for all members of the surgical team to visualize a wide spectrum of the integrated intraoperative information related to the condition of the patient, nuances of the surgical procedure, and details of the cortical mapping, practically without interruption of the surgical manipulations. The wide set of both anatomical and functional parameters, such as view of the patient's mimic and face movements while answering the specific questions, type of the examination test, position of the surgical instruments, parameters of the bispectral index monitor, and general view of the surgical field through the operating microscope, is presented compactly in one screen with several displays. However, the initially designed IEMAS system was occasionally affected by interruption or detachment of the connecting cables, which sometimes interfered with its effective clinical use. Therefore, a new modification of the device was developed. The specific feature is installation of wireless information transmitting technology using audio-visual transmitters and receivers for transfer of images and verbal information. The modified IEMAS system is very convenient to use in the narrow space of the operating room.
Hitchhikers need free vehicles! (2016)

As a means for improving the maturity of the data analysis methods used in the search-based software testing field, this paper presents the need for shared repositories of well-documented statistical analysis code and replication data. In addition to explaining the benefits associated with using these repositories, the paper gives suggestions (e.g., the testing of analysis code) for improving the study of data arising from experiments with randomized algorithms.
Simultaneous Reduction Techniques of Nitrous and Nitrogen Oxides from Fluidized-Bed Coal Combustor. (1995)

気泡流動層石炭燃焼装置からの亜酸化窒素 (N2O) と窒素酸化物 (NOx) の同時低減法について, 内径が約16cmのベンチスケール装置を使って実験的に評価・検討した.まず赤泥, 酸化カルシウム, 水酸化カルシウムおよび酸化マグネシウムなどの微粉粒子を石炭と一緒またはサイクロン直前の煙道に供給して接触効果を調べた.結果として, これらの粒子はN2O分解の効果が少ない一方でNOxの増加をもたらした.炉頂にプロパンガスを吹き込み過剰空気で燃焼する排ガス加熱法の場合もNOx発生量が増加した.2段燃焼法はN2OとNOxの同時低減に効果的であったが, 低減率は40%以下であった.2段燃焼の効果を高めるための新しい燃焼法として, 1次燃焼部を空気不足状態に保ったまま2次燃焼部にプロパンガスとプロパンガスの量論空気量よりも少ない空気とを吹き込み, さらに3次空気をフリーボード上部に吹き込む改良型3段燃焼法を検討した.この方式ではフリーボードの最高温度が925℃程度でN2Oの低減率が85%以上にも達し, さらにNOx発生量も2段燃焼法より少なくなった.したがって, ここで新しく提案した改良型3段燃焼法は現時点で最良の同時低減法といえる.
Total hCG Versus Free β-hCG Combined with Alpha-fetoprotein for Down Syndrome Screening in Taiwan (2007)

The measurement of free beta-hCG is more beneficial than total hCG in serum screening for Down syndrome during the second trimester of pregnancy.
Direct additive genetics and maternal effect contribute to the risk of Tourette disorder (2023)

Our results demonstrate genetic maternal effect contributes to the risk of CTD. Failure to account for maternal effect results in an incomplete understanding of the genetic risk architecture of CTD, as the risk for CTD is impacted by maternal effect which is above and beyond the risk from transmitted genetic effect.