bluuebunny/crossref_metadata_2025 huggingface dataset:
Pattern Detection in Multiple Genome Sequences with Applications: The Case of All SARS-CoV-2 Complete Variants
Authors: Xylogiannopoulos Konstantinos F.
Published: April 2021

Pattern detection and string matching are fundamental problems in computer science and the accelerated expansion of bioinformatics and computational biology have made them a core topic for both disciplines. The SARS-CoV-2 pandemic has made such problems more demanding with hundreds or thousands of new genome variants discovered every week, because of constant mutations, and the need for fast and accurate analyses. Medicines and, mostly, vaccines must be altered to adapt and efficiently address mutations. The need of computational tools for genomic analysis, such as sequence alignment, is very important, although, in most cases the resources and computational power needed is vast. The presented data structures and algorithms, specifically built for text mining and pattern detection, can help to address efficiently several bioinformatics problems. With a single execution of advanced algorithms, with limited space and time complexity, it is possible to acquire knowledge on all repeated patterns that exist in multiple genome sequences and this information can be used for further meta analyses. The potentials of the presented solutions are demonstrated with the analysis of more than 55,000 SARS-CoV-2 genome sequences (collected on March 10, 2021) and the detection of all repeated patterns with length up to 60 nucleotides in these sequences, something practically impossible with other algorithms due to its complexity. These results can be used to help provide answers to questions such as all variants common patterns, sequence alignment, palindromes and tandem repeats detection, genome comparisons, etc.
T1TAdb: the database of Type I Toxin-Antitoxin systems
Authors: Tourasse Nicolas J. , Darfeuille Fabien
Published: April 2021

Type I toxin-antitoxin (T1TA) systems constitute a large class of genetic modules with antisense RNA (asRNA)-mediated regulation of gene expression. They are widespread in bacteria and consist of an mRNA coding for a toxic protein and a noncoding asRNA that acts as an antitoxin preventing the synthesis of the toxin by directly basepairing to its cognate mRNA. The co- and post-transcriptional regulation of T1TA systems is intimately linked to RNA sequence and structure, therefore it is essential to have an accurate annotation of the mRNA and asRNA molecules to understand this regulation. However, most T1TA systems have been identified by means of bioinformatic analyses solely based on the toxin protein sequences, and there is no central repository of information on their specific RNA features. Here we present the first database dedicated to type I TA systems, named T1TAdb. It is an open-access web database (https://d-lab.arna.cnrs.fr/t1tadb) with a collection of ~1,900 loci in ~500 bacterial strains in which a toxin-coding sequence has been previously identified. RNA molecules were annotated with a bioinformatic procedure based on key determinants of the mRNA structure and the genetic organization of the T1TA loci. Besides RNA and protein secondary structure predictions, T1TAdb also identifies promoter, ribosome-binding, and mRNA-asRNA interaction sites. It also includes tools for comparative analysis, such as sequence similarity search and computation of structural multiple alignments, which are annotated with covariation information. To our knowledge, T1TAdb represents the largest collection of features, sequences, and structural annotations on this class of genetic modules.
Inhibiting Spinal Cord-Specific Hsp90 Isoforms Reveals a Novel Strategy to Improve the Therapeutic Index of Opioid Treatment
Authors: Duron David I. , Campbell Christopher S. , Chou Kerry , Tanguturi Parthasaradhireddy , Bejarano Paul , Gabriel Katherin A. , Bowden Jessica L. , Mishra Sanket , Brackett Christopher , Barlow Deborah , Houseknecht Karen L. , Blagg Brian S.J. , Streicher John M.
Published: April 2021

Opioid drugs like morphine are the gold standard for the treatment of chronic pain, but are limited by adverse side effects, such as tolerance, constipation, and reward/addiction. In our earlier work, we showed that Heat shock protein 90 (Hsp90) has a crucial role in regulating opioid signaling that differs between brain and spinal cord; Hsp90 inhibition in brain blocks opioid pain relief, while inhibition in the spinal cord enhances it. Building on these findings here, we injected the non-selective Hsp90 inhibitor KU-32 directly into the spinal cord of male and female CD-1 mice, showing that morphine anti-nociceptive potency was boosted by 1.9-3.5 fold in the pain models of tail flick, post-surgical paw incision, and HIV peripheral neuropathy. At the same time, morphine tolerance was reduced from 21 fold to 2.9 fold and established tolerance was rescued, while the potency of constipation and reward (as measured by conditioned place preference) was unchanged. These results demonstrate that spinal Hsp90 inhibition can improve the therapeutic index of morphine. However, we also found that systemic non-selective Hsp90 inhibition resulted in a brain-like effect, blocking opioid pain relief. We thus sought a way to circumvent the effects of brain Hsp90 inhibition by investigating the molecular Hsp90 isoforms active in regulating opioid signaling in both regions. Using selective small molecule inhibitors and CRISPR gene editing, we found that 3 Hsp90 isoforms regulated spinal cord opioid signaling (Hsp90α, Hsp90β, and Grp94) while our previous work showed only Hsp90α was active in brain. We thus hypothesized that a systemically delivered selective inhibitor to Hsp90β or Grp94 could selectively inhibit spinal cord Hsp90 activity, resulting in enhanced opioid pain relief and decreased side effects. We tested this hypothesis using intravenous delivery of KUNB106 (Hsp90β) and KUNG65 (Grp94), showing that both drugs enhanced morphine potency in tail flick and paw incision pain while rescuing anti-nociceptive tolerance. We also found that intravenous KUNA115 (Hsp90α) fully blocked morphine anti-nociception. Together, these results suggest that selective inhibition of spinal cord Hsp90 isoforms is a novel, translationally feasible strategy to improve the therapeutic index of opioids.
Reduced graphene oxide membrane as supporting film for high-resolution cryo-EM
Authors: Liu Nan , Zheng Liming , Xu Jie , Wang Jia , Hu Cuixia , Lan Jun , Zhang Xing , Zhang Jincan , Xu Kui , Cheng Hang , Yang Zi , Gao Xin , Wang Xinquan , Peng Hailin , Chen Yanan , Wang Hong-Wei
Published: April 2021

Although single-particle cryogenic electron microscopy (cryo-EM) has been applied extensively for elucidating many crucial biological mechanisms at the molecular level, this technique still faces critical challenges, the major one of which is to prepare the high-quality cryo-EM specimen. Aiming to achieve a more reproducible and efficient cryo-EM specimen preparation, novel supporting films including graphene-based two-dimensional materials have been explored in recent years. Here we report a robust and simple method to fabricate EM grids coated with single- or few-layer reduced graphene oxide (RGO) membrane in large batch for high-resolution cryo-EM structural determination. The RGO membrane has decreased interlayer space and enhanced electrical conductivity in comparison to regular graphene oxide (GO) membrane. Moreover, we found that the RGO supporting film exhibited nice particle-absorption ability, thus avoiding the air-water interface problem. More importantly, we found that the RGO supporting film is particularly useful in cryo-EM reconstruction of sub-100 kDa biomolecules at near-atomic resolution, as exemplified by the study of RBD-ACE2 complex and other small protein molecules. We envision that the RGO membranes can be used as a robust graphene-based supporting film in cryo-EM specimen preparation.
Generation of guard cell RNA-seq transcriptomes during progressive drought and recovery using an adapted INTACT protocol forArabidopsis thalianashoot tissue
Authors: van Weringh Anna , Pasha Asher , Esteban Eddi , Gamueda Paul J. , Provart Nicholas J.
Published: April 2021

Drought is an important environmental stress that limits crop production. Guard cells (GC) act to control the rate of water loss. To better understand how GCs change their gene expression during a progressive drought we generated guard cell-specific RNA-seq transcriptomes during mild, moderate, and severe drought stress. We additionally sampled re-watered plants that had experienced severe drought stress. These transcriptomes were generated using the INTACT system to capture the RNA from GC nuclei. We optimized the INTACT protocol forArabidopsis thalianaleaf tissue, incorporating fixation to preserve RNA during nuclear isolation. To be able to identify gene expression changes unique to GCs, we additionally generated transcriptomes from all cell types, using a 35S viral promoter to capture the nuclei of all cell types in leaves. These data sets highlight shared and unique gene expression changes between GCs and the bulk leaf tissue. The timing of gene expression changes is different between GCs and other cell types: we found that only GCs had detectable gene expression changes at the earliest drought time point. The drought responsive GC and leaf RNA-seq transcriptomes are available in the Arabidopsis ePlant at the Bio-Analytic Resource for Plant Biology website.
Phosphorylation of phosphoglucomutase 1 on a peripheral site tunes its activity to regulate glycogen metabolism
Authors: Doello Sofía , Neumann Niels , Forchhammer Karl
Published: April 2021

Regulation of glycogen metabolism is of vital importance in organisms of all three kingdoms of life. Although the pathways involved in glycogen synthesis and degradation are well known, many regulatory aspects around the metabolism of this polysaccharide remain undeciphered. Here, we used the unicellular cyanobacteriumSynechocystisas a model to investigate how glycogen metabolism is regulated in nitrogen-starved dormant cells, which entirely rely on glycogen catabolism to resume growth upon nitrogen repletion. We identified phosphoglucomutase 1 (PGM1) as a key regulatory point in glycogen metabolism, and post-translational modification as an essential mechanism for controlling its activity. We could show that PGM1 is phosphorylated at a peripheral residue (Ser 47) during nitrogen starvation, which inhibits its activity. Inactivation of PGM1 by phosphorylation at Ser 47 prevents premature degradation of the glycogen stores and appears to be essential for survival ofSynechocystisin the dormant state. Remarkably, this regulatory mechanism seems to be evolutionary conserved in PGM1 enzymes, from bacteria to humans.

Significance statement

In this study, we identified phosphoglucomutase 1 (PGM1) as a central metabolic valve that regulates the utilization of the glycogen reserves. We showed that post-translational modification of PGM1 via phosphorylation at a peripheral residue is a key, evolutionary-conserved regulatory mechanism that controls PGM1 activity and the mobilization of the glycogen stores.
Deep mutational scanning of the plasminogen activator inhibitor-1 functional landscape
Authors: Huttinger Zachary M. , Haynes Laura M. , Yee Andrew , Kretz Colin A. , Siemieniak David R. , Lawrence Daniel A. , Ginsburg David
Published: April 2021

The serine protease inhibitor (SERPIN) plasminogen activator inhibitor-1 (PAI-1) is a key regulator of the fibrinolytic system, inhibiting the serine proteases tissue- and urokinase-type plasminogen activator (tPA and uPA, respectively). Missense variants may render PAI-1 non-functional through misfolding, leading to its turnover as a protease substrate, or to a more rapid transition to the latent/inactive state. Deep mutational scanning was performed to evaluate the impact of amino acid sequence variation on PAI-1 inhibition of uPA using an M13 filamentous phage display system. The effects of single amino acid substitutions on PAI-1’s functional inhibition of its canonical target proteases, tPA and uPA, have been determined for only a small fraction of potential mutations. To construct a more comprehensive dataset, a mutagenized PAI-1 library, encompassing ∼70% of potential single amino acid substitutions, was displayed on M13 filamentous phage. From this library, the relative effects of 27% of all possible missense variants on PAI-1 inhibition of urokinase-type plasminogen activator were determined using high-throughput DNA sequencing with 826 missense variants demonstrating conserved inhibitory activity and 1137 resulting in loss of PAI-1 function. Comparison of these deep mutational scanning results to predictions from PolyPhen-2 and SIFT demonstrate the limitations of these algorithms, consistent with similar reports for other proteins. Comparison to common human PAI-1 gene variants present in the gnomAD database is consistent with evolutionary selection against loss of PAI-1 function. These findings provide insight into structure-function relationships for PAI-1 and other members of the SERPIN superfamily.
The mode of expression divergence in Drosophila fat body is infection-specific
Authors: Ramirez-Corona Bryan A. , Fruth Stephanie , Ofoegbu Oluchi , Wunderlich Zeba
Published: April 2021

Transcription is controlled by interactions of cis-acting DNA elements with diffusible trans-acting factors. Changes in cis or trans factors can drive expression divergence within and between species, and their relative prevalence can reveal the evolutionary history and pressures that drive expression variation. Previous work delineating the mode of expression divergence in animals has largely used whole-body expression measurements in one condition. Because cis-acting elements often drive expression in a subset of cell types or conditions, these measurements may not capture the complete contribution of cis-acting changes. Here, we quantify the mode of expression divergence in the Drosophila fat body, the primary immune organ, in several conditions, using two geographically distinct lines of D. melanogaster and their F1 hybrids. We measured expression in the absence of infection and in infections with Gram-negative S. marcescens or Gram-positive E. faecalis bacteria, which trigger the two primary signaling pathways in the Drosophila innate immune response. The mode of expression divergence strongly depends on the condition, with trans-acting effects dominating in response to Gram-negative infection and cis-acting effects dominating in Gram-positive and preinfection conditions. Expression divergence in several receptor proteins may underlie the infection-specific trans effects. Before infection, when the fat body has a metabolic role, there are many compensatory effects, changes in cis and trans that counteract each other to maintain expression levels. This work shows that within a single tissue, the mode of expression divergence varies between conditions and suggests that these differences reflect the diverse evolutionary histories of host–pathogen interactions.
Trajectory mapping of the early Drosophila germline reveals controls of zygotic activation and sex differentiation
Authors: Li Yi-Ru , Lai Hsiao Wen , Huang Hsiao Han , Chen Hsing-Chun , Fugmann Sebastian D. , Yang Shu Yuan
Published: April 2021

Germ cells in Drosophila melanogaster are specified maternally shortly after fertilization and are transcriptionally quiescent until their zygotic genome is activated to sustain further development. To understand the molecular basis of this process, we analyzed the progressing transcriptomes of early male and female germ cells at the single-cell level between germline specification and coalescence with somatic gonadal cells. Our data comprehensively cover zygotic activation in the germline genome, and analyses on genes that exhibit germline-restricted expression reveal that polymerase pausing and differential RNA stability are important mechanisms that establish gene expression differences between the germline and soma. In addition, we observe an immediate bifurcation between the male and female germ cells as zygotic transcription begins. The main difference between the two sexes is an elevation in X Chromosome expression in females relative to males, signifying incomplete dosage compensation, with a few select genes exhibiting even higher expression increases. These indicate that the male program is the default mode in the germline that is driven to female development with a second X Chromosome.
Awareness of errors and feedback in human time estimation
Authors: Bader Farah , Wiener Martin
Published: April 2021

Behavioral and electrophysiology studies have shown that humans possess a certain self-awareness of their individual timing ability. However, conflicting reports raise concerns about whether humans can discern the direction of their timing error, calling into question the extent of this timing awareness. To understand the depth of this ability, the impact of nondirectional feedback and reinforcement learning on time perception were examined in a unique temporal reproduction paradigm that involved a mixed set of interval durations and the opportunity to repeat every trial immediately after receiving feedback, essentially allowing a “redo.” Within this task, we tested two groups of participants on versions where nondirectional feedback was provided after every response, or not provided at all. Participants in both groups demonstrated reduced central tendency and exhibited significantly greater accuracy in the redo trial temporal estimates, showcasing metacognitive ability, and an inherent capacity to adjust temporal responses despite the lack of directional information or any feedback at all. Additionally, the feedback group also exhibited an increase in the precision of responses on the redo trials, an effect not observed in the no-feedback group, suggesting that feedback may specifically reduce noise when making a temporal estimate. These findings enhance our understanding of timing self-awareness and can provide insight into what may transpire when this is disrupted.
Sleep strengthens integration of spatial memory systems
Authors: Noack Hannes , Doeller Christian F. , Born Jan
Published: April 2021

Spatial memory comprises different representational systems that are sensitive to different environmental cues, like proximal landmarks or local boundaries. Here we examined how sleep affects the formation of a spatial representation integrating landmark-referenced and boundary-referenced representations. To this end, participants (n = 42) were familiarized with an environment featuring both a proximal landmark and a local boundary. After nocturnal periods of sleep or wakefulness and another night of sleep, integration of the two representational systems was tested by testing the participant's flexibility to switch from landmark-based to boundary-based navigation in the environment, and vice versa. Results indicate a distinctly increased flexibility in relying on either landmarks or boundaries for navigation, when familiarization to the environment was followed by sleep rather than by wakefulness. A second control study (n = 45) did not reveal effects of sleep (vs. wakefulness) on navigation in environments featuring only landmarks or only boundaries. Thus, rather than strengthening isolated representational systems per se, sleep presumably through forming an integrative representation, enhances flexible coordination of representational subsystems.
Visual object recognition is facilitated by temporal community structure
Authors: Kakaei Ehsan , Aleshin Stepan , Braun Jochen
Published: April 2021

Humans and others primates are highly attuned to temporal consistencies and regularities in their sensory environment and learn to predict such statistical structure. Moreover, in several instances, the presence of temporal structure has been found to facilitate procedural learning and to improve task performance. Here we extend these findings to visual object recognition and to presentation sequences in which mutually predictive objects form distinct clusters or “communities.” Our results show that temporal community structure accelerates recognition learning and affects the order in which objects are learned (“onset of familiarity”).
Short-term memory reactivation of a weak CS–US association promotes long-term memory persistence in conditioned odor aversion
Authors: Tovar-Díaz Jorge , Morín Jean-Pascal , Ríos-Carrillo Jorge Eduardo , Sánchez de Jesús Hilda , Roldán-Roldán Gabriel
Published: April 2021

In conditioned odor aversion (COA), the association of a tasteless odorized solution (the conditioned stimulus [CS]) with an intraperitoneal injection of LiCl (the unconditioned stimulus [US[), which produces visceral malaise, results in its future avoidance. The strength of this associative memory is mainly dependent on two parameters, that is, the strength of the US and the interstimuli interval (ISI). In rats, COA has been observed only with ISIs of ≤15 min and LiCl (0.15 M) doses of 2.0% of bodyweight, when tested 48 h after acquisition (long-term memory [LTM]). However, we previously reported a robust aversion in rats trained with ISIs up to 60 min when tested 4 h after acquisition (short-term memory [STM]). Since memories get reactivated during retrieval, in the current study we hypothesized that testing for STM would reactivate this COA trace, strengthening its LTM. For this, we compared the LTM of rats trained with long ISIs or low doses of LiCl initially tested for STM with that of rats tested for LTM only. Interestingly, rats conditioned under parameters sufficient to produce STM, but not LTM, showed a reliable LTM when first tested for STM. These observations suggest that under suboptimal training conditions, such as long ISIs or low US intensities, a CS–US association is established but requires reactivation in the short-term in order to persist in the long-term.
Crystal structure and Hirshfeld surface analysis of 2-{[7-acetyl-8-(4-chlorophenyl)-4-cyano-6-hydroxy-1,6-dimethyl-5,6,7,8-tetrahydroisoquinolin-3-yl]sulfanyl}-N-(4-chlorophenyl)acetamide
Authors: Akkurt Mehmet , Marae Islam S. , Mague Joel T. , Mohamed Shaaban K. , Bakhite Etify A. , Al-Waleedy Safiyyah A. H.
Published: April 2021

In the title molecule, C28H25Cl2N3O3S, the heterocyclic portion of the tetrahydroisoquinoline unit is planar while the cyclohexene ring adopts a twist-boat conformation. The two 4-chlorophenyl groups extend away from one side of this unit while the hydroxyl and acetyl groups extend away from the opposite side and form an intramolecular O—H...O hydrogen bond. The crystal packing consists of layers parallel to the bc plane. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H...H (37.3%), Cl...H/H...Cl (17.6%), O...H/H...O (11.1%), C...H/H...C (10.9%) and N...H/H...N (9.7%) interactions.
WMS: Revenue Model Innovation for Gaming Solutions
Authors: Sawhney Mohanbir , Goodman Pallavi , Broit Ori
Published: April 2021

In 2014 WMS Gaming, a manufacturer and seller of slot machines to casinos, was considering a redesign of its existing revenue model. As technology evolved and customer demand for gaming solutions intensified, new and innovative revenue models were being adopted in other technology markets. Most notably, the subscription revenue model, in which customers paid a monthly subscription fee rather than a large upfront fee, was becoming widely adopted in the software industry. Product manager Dayna Stone had the task of evaluating several revenue models and recommending one that most suited WMS's business needs and at the same time took customer needs and wishes into consideration. Complicating this decision were several factors that would have to be kept in mind. Americans' love of gaming had led to a mushrooming of casinos, which meant increased competition for casino dollars. Yet the financial crisis of 2008 and its aftermath had weakened demand for casinos. In addition, casinos, depending on the type of customers they attracted, differed in their appetite for innovation and maintenance of their slot machines. Students will step into the shoes of Dayna Stone as she undertakes the task of weighing these factors and selecting the right revenue model.
Kheyti: Product and Business Development at an AgTech Social Enterprise
Authors: Sawhney Mohanbir , Saumya
Published: April 2021

In early 2017, after launching its successful “Greenhouse-in-a-Box” pilot project in India with fifteen smallholder farmers, Kheyti, a non-profit agricultural technology (AgTech) social enterprise, was struggling with several decisions in developing and growing its business. Kheyti was launched in 2015 to help smallholder farmers battle poverty and income variability by providing affordable technologies bundled with services. Over eighteen months, the team had developed a low-cost and modular greenhouse product to which it added financing, inputs, training, and market linkages to create a comprehensive “full-stack” solution for small farmers. The pilot project was a success in many ways, but Saumya, Kheyti's co-founder and head of product, was concerned that it revealed shortcomings that could severely affect the viability and scalability of Kheyti's solution.

Saumya had some important decisions to make. Should Kheyti redesign the product from scratch, or find other ways to reduce the cost for early adopters? Should it rely on upfront revenues from sales of the greenhouse, or consider developing an innovative financing or contract farming model? Kheyti's dwindling cash reserves meant that these decisions were urgent and critical. The path chosen now would determine whether the startup would move beyond the pilot stage and achieve its vision of serving 1 million farmers by 2025.
Chlorhexidine Adoption in Nigeria
Authors: Palamountain Kara , Calkins Tim
Published: April 2021

It is January 2017, and Nikki Tyler, market access advisor at the U.S. Agency for International Development's Center for Accelerating Innovation and Impact, must recommend an actionable strategy for how to use the $10 million contributed by global donors and foundations to scale up the use of chlorhexidine in Nigeria. It was clear that chlorhexidine, a substance applied to newborns' umbilical cord stumps to prevent infection, could reduce infant mortality significantly. However, changing behavior would be an enormous challenge. This case gives students an appreciation for the importance and complexity of global health issues, along with an understanding of key analytic techniques for approaching a complex market situation. Students quickly learn that there are no easy answers to encouraging chlorhexidine's greater use. To develop a plan, it is essential to complete detailed analyses, study insights and motivations, and ultimately compare different possible solutions, considering efficiency and efficacy.
Cause and Effect: Performance Attribution in Commercial Real Estate
Authors: Furfine Craig
Published: April 2021

In April 2015, Shannon Enberg, Managing Director of Real Assets at the United Kingdom Telecom and Technology Pension Scheme (UKTTPS), received a startling memo from the fund's board of directors. In a nutshell, the board sought to reduce the fund's multimillion-pound annual expenditure on management fees by asking all managing directors to drastically cut the number of private managers being used to manage UKTTPS assets. Enberg was told to cut the number of her external managers in half, but given the illiquidity of her private equity investments in commercial property, she would be allowed to make the decision to rehire each manager (or not) as each of her investments matured. UKTTPS had two investments in closed-end property funds that had just liquidated their final holdings at the end of 2014. Both managers had new funds being raised that could recycle the investment proceeds, but now that she was being forced to cut back, Enberg wondered whether either was really worth rehiring.
CEMEX: Information Technology, an Enabler for Building the Future
Authors: Walker Russell
Published: April 2021

The case examines the role of IT in CEMEX, a giant Mexican building materials manufacturer in an industry categorized by low margins and high costs. In the early 1990s, CEMEX made significant investments in its IT systems, resulting in a data-based management operation that put it at the forefront of the industry. As the company grew through acquisitions, it integrated IT through “The CEMEX Way,” a set of standardized processes, organizations, and systems implemented on a common IT platform.

In 2007, when CEMEX acquired Rinker, a major Australian concrete company, aligning Rinker with CEMEX IT systems was critical to quickly streamline operations and realize efficiencies. The CIO of CEMEX had developed a new integration process called Processes & IT (P&IT) that he was considering using for the Rinker integration. However, P&IT required additional resources, including significant upfront fixed costs and investment in new personnel teams at a time when the company was already struggling with the integration of another acquisition. CEMEX could either align Rinker to The CEMEX Way or use the opportunity to invest significantly more in evolving to the new P&IT approach that focused on business process management.
Uber China
Authors: Tybout Alice M.
Published: April 2021

Uber China is a strategy pricing case that examines the role of customer acquisition tactics and brand positioning in entering the tantalizingly large Chinese market. The case adopts the perspective of an outside observer looking at Uber's efforts to compete in China from its entry in 2013 to its exit through its acquisition by Didi Chuxing, the highly dominant industry leader in China's ride-sharing market. After laying out the market opportunity, consumer and competitive landscape, and the various acquisition-related moves of Uber and the other major players, the case asks students to conduct a postmortem on Uber's failure in China. Specifically, they must consider what drew Uber to the opportunity in China and what it might have done differently in terms of positioning and customer acquisition to compete more effectively. First and foremost a pricing-related discussion, the case illustrates the relationship between pricing and acquisition tactics and brand positioning and the use of both in market entry and penetration.
Pregnancy outcomes following different protocols of controlled ovarian hyperstimulation in couples undergoing intrauterine insemination
Authors: Taiyeb Ahmed M. , Haji Azheen I. , Ibraheem Zaid O. , Alsakkal Ghada S.
Published: April 2021

Clomiphene citrate (CC), letrozole and cetrorelix acetate are frequently used agents in controlled ovarian hyperstimulation (COH). However, these three agents have not yet been compared to one another regarding their pregnancy outcomes. The present study was designed to retrospectively compare pregnancy outcomes among the three aforementioned agents. This study involved infertile couples with an infertility duration of at least 2 years, ages 18 to 42 years and who were referred to have their first intrauterine insemination (IUI) treatment cycle. All patients underwent COH with recombinant follicle‐stimulating hormone (rFSH) plus CC (n = 118), letrozole (n = 81), or cetrorelix acetate (n = 62), followed by IUI. Using the one‐way multivariate analysis of covariance to control female patients’ ages, patients stimulated with cetrorelix acetate/rFSH or CC/rFSH had higher numbers of preovulatory follicles than women stimulated with letrozole/rFSH (P < .02), whereas women stimulated with cetrorelix acetate/rFSH had a thicker endometrium than women stimulated with CC/rFSH (P < .0005). Biochemical pregnancy rates were similar among the three protocols of COH. However, women stimulated with letrozole/rFSH showed clinical pregnancy rates higher than those stimulated with CC/rFSH (P = .003) or cetrorelix acetate/rFSH (P = .03) and subclinical abortion rates lower than those stimulated with CC/rFSH or cetrorelix acetate/rFSH (P = .009). Of the different protocols of COH, the odds of having a clinical pregnancy was 3.1 times greater for women stimulated with letrozole/rFSH than women stimulated with CC/rFSH (P = .004) and 2.8 times greater for women stimulated with letrozole/rFSH than women stimulated with cetrorelix acetate/rFSH (P = .03). Our observations show that increased numbers of preovulatory follicles or endometrium thickness do not necessarily improve pregnancy outcomes, because pregnancy outcomes are also subjected to the type of COH used agent. In this regard, letrozole produced fewer preovulatory follicles and did not significantly increase endometrium thickness, but significantly improved pregnancy outcomes in comparison to CC and cetrorelix acetate.
Reassessing the magnitude of housing price declines and the use of leverage in the Depressions of the 1890s and 1930s
Authors: Rose Jonathan D.
Published: April 2021

This paper presents the first repeat sales index for residential housing in any U.S. city spanning the late 19th and early 20th centuries, covering Baltimore from 1880 to 1953. Compared to previous data, the index shows larger declines in housing prices during the Depressions of the 1890s and 1930s. I also find higher leverage entering into those periods than previously understood. I conclude that negative equity in the 1930s was a bigger problem than implied by existing data, rationalizing the extent of foreclosures that occurred.
Dosimetric and clinical outcomes of SpaceOAR in men undergoing external beam radiation therapy for localized prostate cancer: A systematic review
Authors: Babar Mustufa , Katz Alan , Ciatto Michael
Published: April 2021

SpaceOAR, an absorbable polyethylene glycol hydrogel, increases the space between the prostate and rectum to reduce the radiation received by the rectum during prostate cancer radiation therapy. The objective of this systematic review was to evaluate controlled studies on the dosimetric and clinical outcomes of SpaceOAR in men undergoing external beam radiation therapy for localized prostate cancer. Eight studies were included in the review. All of the studies showed SpaceOAR to reduce the radiation dose volume to the rectum over numerous dosimetry levels. Of the four studies that assessed toxicity, one reported SpaceOAR to significantly decrease acute Grade 1 diarrhoea and two reported SpaceOAR to significantly decrease late Grade 1 and Grade ≥2 rectal toxicities. Two studies assessed cumulative incidence of toxicity at 3 years in which one reported SpaceOAR to significantly decrease urinary incontinence and Grade ≥1 and Grade ≥2 rectal toxicities, and the other reported SpaceOAR to significantly decrease Grade 1 diarrhoea and Grade 2 proctitis. Moreover, one study reported that fewer SpaceOAR patients experienced 10‐point declines in bowel quality of life at 3 years, but another study reported no significant difference in 10‐point declines in bowel quality of life between the SpaceOAR and control groups at 5 years. With the current research available, SpaceOAR may be beneficial to those who did not meet the standard rectal dose‐volume criteria, have higher risk factors of developing rectal toxicities post‐radiation, or wish to decrease the length and costs of radiotherapy by increasing the dose of radiation per fraction.
Association between deficient levels of circulating vitamin D, dietary intake of vitamin D, calcium and retinol, and risk of colorectal cancer in an Iranian population: A case control study
Authors: Abbasnezhad Amir , Falahi Ebrahim , Ghavamzadeh Saeid , Beiranvand Ramin , Talaiezadeh Abdolhassan , Hasanvand Amin , Angali Kambiz Ahmadi , Choghakhori Razieh
Published: April 2021

Aim

We aimed to assess the association between deficient levels of circulating vitamin D, dietary intake of vitamin D, calcium and retinol, and risk of colorectal cancer in an Iranian population.

Methods

In this retrospective case‐control study that was conducted between 2012 and 2015, 278 first incident colorectal cancer cases (colon cancer = 103; rectal cancer = 175), and 278 sex and age matched healthy controls (HCs) were recruited. Serum 25(OH)D, dietary vitamin D, and calcium intake were assessed. Logistic regression was used to estimate the odds ratio (OR) between studied factors and colorectal cancer. Estimates of OR were calculated according to both bivariate analyses based on the matching factors and multivariate analyses, with additional adjustment for potential confounders.

Results

A strong inverse linear dose‐response association was seen between serum 25(OH)D and colorectal cancer (P for trend = .002). In comparison to serum 25(OH)D more than 40 nmol/L, lower serum concentrations were significantly associated with an increased OR of colorectal cancer. When analyzing anatomical subsites separately, lower circulating 25(OH)D was associated with higher OR for both colon and rectum cancers. Dietary vitamin D and calcium intake were not associated with colorectal cancer. Interaction analysis between serum 25(OH)D and the amount of calcium intake demonstrated that the lowest level of both factors was associated with an increased OR of colorectal cancer. The highest OR of colorectal cancer that was associated with lowest circulating 25(OH)D was stronger at the highest retinol intakes.

Conclusion

This study demonstrated an inverse strong association between 25(OH)D concentration and colorectal cancer in an Iranian population.
The impact of microfinance on poverty and income inequality in developing countries
Authors: Subramaniam Yogeeswari , Masron Tajul Ariffin , Wahab Mastura A. , Mia Md Aslam
Published: April 2021

Economic growth in developing countries provides an opportunity to accelerate progress towards the UN Sustainable Development Goals (SDGs). However, in reality, the number of people living in extreme poverty remains unacceptably high. Utilising the experiences of 34 developing countries for the period 2009 to 2016, the role of microfinance on poverty in these countries is examined. The results imply that the degree to which the existing forms of microfinance effectively reduce extreme poverty is less workable in developing countries, particularly when the hardcore poor are likely being deprived of receiving access to microfinance. It is suggested that governments may need to revise the structure and strategy of microfinance to be more hardcore poor oriented. The hardcore poor have needs beyond pure monetary assistance. More hand‐holding types of assistance are needed as most are also poor in respect of literacy, assets, and skills.
Vaginal NOTES surgery in patients with prior hysterectomy: A first case series
Authors: Vanhooren Emma , Baekelandt Jan
Published: April 2021

This is a first feasibility on vaginal natural orifice transluminal endoscopic surgery (vNOTES) in patients with prior hysterectomy. Our aim was to gain initial experience on performing vNOTES surgery on prior hysterectomy cases, whereby the main concern is that pelvic adhesions may impede safe transvaginal access. Between January 2017 and February 2020, a single surgeon (J.B.) performed vNOTES surgery on nine patients with a history of hysterectomy. Conventional laparoscopic instruments were inserted transvaginally through a vNOTES port. No abdominal incisions were made. Patient data and perioperative data were analyzed. Mean operating time was 38 minutes and there were no operative complications. Postoperative pain scores were low. The mean size of the adnexal cysts that were removed was 26 mm. In this study, vNOTES surgery was successfully performed in nine patients with prior hysterectomy. Following the IDEAL principles, it is important to report on our initial findings of this IDEAL stage 1 study. The results warrant further investigation in IDEAL stage 2 studies but do not validate the widespread use of this approach.
The effect of high‐dose, short‐term caffeine intake on the renal clearance of calcium, sodium and creatinine in healthy adults
Authors: Reuter Stephanie E. , Schultz Hayley B. , Ward Michael B. , Grant Crystal L. , Paech Gemma M. , Banks Siobhan , Evans Allan M.
Published: April 2021

The consumption of caffeine has been linked to osteoporosis, believed to be due to enhanced bone resorption as a result of increased calcium excretion in the urine. However, the amount of calcium in the urine may not necessarily reflect the true effect of caffeine on calcium clearance. This study therefore examined the impact of high‐dose, short‐term caffeine intake on renal clearance of calcium, sodium and creatinine in healthy adults. In a double‐blind clinical study, participants chewed caffeine (n = 12) or placebo (n = 12) gum for 5 minutes at 2‐hour intervals over a 6‐hour treatment period (800 mg total caffeine). Caffeine increased renal calcium clearance by 77%. Furthermore, the effect was positively correlated with sodium clearance and urine volume, suggesting that caffeine may act through inhibition of sodium reabsorption in the proximal convoluted tubule. This study confirmed that caffeine does increase renal calcium clearance and fosters further investigation into safe consumption of caffeine.
Prenatal tobacco and postbirth second‐hand smoke exposure and dental caries in children
Authors: Dearing Bianca A. , Katz Ralph V. , Weitzman Michael
Published: April 2021

Objectives

Second‐hand smoke (SHS) exposure has been identified as a risk factor for several childhood health problems including dental caries. The purpose of this study was to examine the association of postbirth SHS exposure and dental caries and to determine whether the association is independent of prenatal tobacco exposure, sugar consumption and dental utilization.

Methods

NHANES 2013‐2014 and 2015‐2016 were used to examine the research question in 1733 children, 4‐11 years old with full primary or mixed dentition and serum cotinine levels below 10 ng/mL. Weighted multivariable logistic regression models were developed to examine the independent association between SHS exposure and the prevalence of (i) any dental caries experience and (ii) any decayed teeth.

Results

Children exposed to postbirth SHS differed from children not exposed regarding decayed teeth prevalence in the total sample (OR = 1.80, 95% CI: 1.20, 2.71) and mixed dentition (OR = 1.86, 95% CI: 1.20, 2.90) after confounder adjustment. However, no association was found in the primary dentition or between SHS exposure and total caries experience.

Conclusions

The findings partially show that postbirth SHS is associated with dental caries in children. However, the inconsistencies in findings across the three samples and between the two outcome measures, dental caries experience and decayed teeth prevalence raise questions regarding the validity of the hypothesis. Further, the findings suggest that postbirth SHS is likely a marker for true causes of dental caries and the association is likely confounded with other factors associated with dental caries.
Validation of the French version of the Cannabis Use Disorder Identification Test—Revised and comparison with the Cannabis Abuse Screening Test for screening cannabis use disorder in a psychiatric sample
Authors: Luquiens Amandine , Berger‐Viergat Aurélie , Larrieu Agathe , Artigaud Laura , Fener Clémentine , Adamson Simon , Laprévote Vincent , Rolland Benjamin
Published: April 2021

Introduction

Several questionnaires have been developed for screening cannabis use disorder in clinical populations, but very few studies have compared the screening abilities of the different instruments. Here, we aimed to confirm the psychometric properties of a French version of the Cannabis Use Disorder Identification Test—Revised (CUDIT‐R), and to compare its screening abilities with those of the Cannabis Abuse Screening Test (CAST), in subjects consulting in mental health settings.

Methods

Two hundred and thirteen cannabis smokers who sought treatment for any type of mental disorder, recruited in four French centres, completed the French CUDIT‐R (CUDIT‐R‐Fr) and the full version of the CAST, and were assessed for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria of cannabis use disorder by an addiction specialist. They were retested with the CUDIT‐R‐Fr after approximately a week. The factorial construct validity, internal consistency and test–retest reliability of the CUDIT‐R‐Fr were assessed. The compared sensitivity and specificity of the CAST and CUDIT‐R‐Fr were explored, using the clinician assessment as the reference.

Results

The French CUDIT‐R showed a good internal consistency (Cronbach's alpha = 0.89) and an excellent test–retest reliability (ρ = 0.97). The sensitivity and specificity for screening cannabis use disorder were 0.81 and 0.77 for the CUDIT‐R, and 0.92 and 0.63 for the CAST, respectively.

Conclusions

Based on the recommended cut‐offs, the CAST appeared more sensitive, while the CUDIT‐R was more specific, for screening cannabis use disorder in a population of cannabis users with heterogeneous types of mental health disorders.
World language programming and leadership in K–12 Massachusetts public schools
Authors: Ritz Catherine , Sherf Nicole
Published: April 2021

This large‐scale study used a survey to collect data on K–12 world language programming in Massachusetts public schools. Building off work by Pufahl and Rhodes (2011), this study focused on world language programs, program types, and languages offered, as well as student exclusion, program leadership, and the Seal of Biliteracy. The study resulted in 188 districts represented in the final data set, which was analyzed using descriptive statistics. Results indicate comparable findings to national data in terms of program and language offerings, with shifts in program type. Data further revealed patterns of student exclusion and trends in offering the Seal of Biliteracy. Although programs are most often led by a world language specialist, school principals are more likely responsible for teacher evaluation. Survey data were collected at the beginning of school closures due to COVID‐19, capturing a picture of K–12 world language education and a point of comparison for future research.
Living on the edge: A continental‐scale assessment of forest vulnerability to drought
Authors: Peters Jennifer M. R. , López Rosana , Nolf Markus , Hutley Lindsay B. , Wardlaw Tim , Cernusak Lucas A. , Choat Brendan
Published: April 2021

Globally, forests are facing an increasing risk of mass tree mortality events associated with extreme droughts and higher temperatures. Hydraulic dysfunction is considered a key mechanism of drought‐triggered dieback. By leveraging the climate breadth of the Australian landscape and a national network of research sites (Terrestrial Ecosystem Research Network), we conducted a continental‐scale study of physiological and hydraulic traits of 33 native tree species from contrasting environments to disentangle the complexities of plant response to drought across communities. We found strong relationships between key plant hydraulic traits and site aridity. Leaf turgor loss point and xylem embolism resistance were correlated with minimum water potential experienced by each species. Across the data set, there was a strong coordination between hydraulic traits, including those linked to hydraulic safety, stomatal regulation and the cost of carbon investment into woody tissue. These results illustrate that aridity has acted as a strong selective pressure, shaping hydraulic traits of tree species across the Australian landscape. Hydraulic safety margins were constrained across sites, with species from wetter sites tending to have smaller safety margin compared with species at drier sites, suggesting trees are operating close to their hydraulic thresholds and forest biomes across the spectrum may be susceptible to shifts in climate that result in the intensification of drought.