bluuebunny/crossref_metadata_2025 huggingface dataset:
Incidence and Risk Factors Associated With Tuberculosis Treatment Outcomes Among Prisoners
Authors: Khan Amer Hayat , Sulaiman Syed Azhar Syed , Muttalif Abdul Razak Abdul , Hassali Mohamed Azmi Ahmad , Aftab Raja Ahsan , Khan Tahir Mehmood
Published: April 2019

Background

Prison represents an important setting for tuberculosis (TB) control. Higher TB rates have been reported in prison when compared with general population.

Aims and objective

The current study evaluates the incidence of TB among prison inmates from 4 states of Malaysia to identify factors associated with Mycobacterium tuberculosis infection and treatment outcomes.

Methodology

A multicenter, cross-sectional, retrospective study was conducted in the 11 prisons in 4 Malaysian states, which were selected based on high burdens of TB in Malaysia (Sabah, Sarawak, Pulau Pinang, and Selangor). Patients with confirmed TB were selected for the study based on tuberculin skin testing and further established by chest radiograph and positive sputum and culture test results.

Results

A total of 405 inmates were diagnosed as having TB, with most them being male inmates (n = 397; 98%). The mean ± SD age of TB inmates was 39.28 ± 10.12 years. The sample was ethnically diverse and consisted mostly of Malays (203; 50.1%) followed by Chinese (98; 24.2%), Indians (64; 15.8%), and other ethnicities (40; 9.9%). Of the total 405 TB inmates, most belonged to the Selangor state prison (n = 312; 77%), with an incidence rate of 755/100,000. The overall incidence of TB among 4 state prisons in Malaysia was 440/100,000. Treatment outcome for 279 (68.8%) TB inmates was successful, 31 (7.7%) were defaulters, 12 (3%) were transferred out, 34 (8.4%) died, and treatment of TB for 49 (12.1%) inmates was continued. On univariate analysis, patient sex (odds ratio [OR], 2.21; 95% confidence interval [CI], 0.2–6.8; P < 0.001), age group (OR, 1.65; CI, 1.08–2.53; P = 0.02), area (OR, 1.08; CI, 0.3–3.1; P < 0.001), pulmonary TB (OR, 1.96; CI, 1.2–3.1; P = 0.05), extrapulmonary TB (OR, 0.53; CI, 0.3–0.8; P = 0.015), and TB with diabetes mellitus (OR, 2.21; CI, 0.7–2.7; P = 0.01) were statistically significant as predictors of treatment outcomes. These variables were further analyzed on multivariate analysis, and patient age group (OR, 1.60; CI, 1.0–2.5; P = 0.02) was a more likely factor that affected treatment outcome.

Conclusion

Low TB treatment success rates and multiple factors affecting treatment outcomes refer to the fact that attention is needed in improving existing medical setup at prisons.
A Retrospective Chart Review on the Clinical Characteristics and Outcomes of Cancer Patients With Group C, F, or G β-Hemolytic Streptococcal Infections
Authors: Shahin Alexander V. , Saba Marian , Greene John N.
Published: April 2019

Background

Infection is a major cause of morbidity and mortality in cancer patients. Gram-positive bacteria account for more than half of all documented bacterial infections in cancer patients, and streptococci are the most frequent pathogen among them. Rarely, group C, F, and G β-hemolytic streptococci have been shown to cause human disease. In this study, we describe the clinical characteristics and outcomes of these infections in cancer patients.

Methods

We performed a retrospective chart review of 157 patients who tested positive for group C, F, or G Streptococcus at the Moffitt Cancer Center between February 2012 and June 2018. Of those 157 patients, 79 were diagnosed as having a true Streptococcus infection. The study population was identified by positive cultures obtained from the microbiology laboratory during the same period.

Results

Of those 79 patients, 67 (85%) had solid tumor malignancies. The leading underlying diseases among these patients were gynecologic cancers (18%), head and neck squamous cell carcinoma (16%), and colorectal cancer (13%). Group G infections (23%) were significantly more common in patients with hematologic malignancies compared with group C or F streptococcal infections (4%). Other bacteria were isolated in 56 patients, the most common being Streptococcus species, Staphylococcus species including methicillin-resistant Staphylococcus aureus, and Pseudomonas aeruginosa. Seventy-two (92%) patients received antibiotics as soon as an infection was suspected, with the most common treatment regimen being a combination of vancomycin and a β-lactam antibiotic to treat polymicrobial infections.

Conclusions

Group C, F, and G streptococci are common pathogens in patients with an underlying malignancy, particularly solid tumor malignancies. Their usual association with other pathogens furthers the need for combinatorial therapeutic strategies to combat polymicrobial infections.
Hepatic Candidiasis in an Immunocompetent Woman
Authors: Gottlieb Lindsey B. , Hashemi Alexandra , Dewar Robert , Salama Carlos
Published: April 2019

Pylephlebitis, or portal vein thrombus infection, is a rare condition that is often missed owing to the nonspecific nature of its signs and symptoms and an underappreciation of the clinical entity. Causative microbes are typically bacteria, although cases of candidal pylephlebitis have been described. Given the invasive technique required to culture the portal vein, antimicrobial selection typically relies on the assumption that the microbes isolated in blood culture are the same as those infecting the portal vein thrombus. We present a case of pylephlebitis in an immunocompetent patient with viridans streptococci and Bacteroides fragilis bacteremia subsequently found to have associated hepatic Candida abscesses. Our case highlights the need to proceed with caution when narrowing antimicrobial therapy for patients with pylephlebitis based on blood culture data alone. It also represents a rare exception to the teaching that hepatic Candida abscesses are only seen in individuals who are profoundly immunocompromised.
Empathy Huddles: Cultivating a Culture of Empathy
Authors: Turner Kevin , Locke Angela , Jones Tina , Carpenter Jacque
Published: April 2019

Managing complex neurological patients challenges new nurses with minimal experience, which can interfere with their ability to relate empathetically to their patients. This article is the story of how 1 neuroscience unit’s experience with Empathy Huddles improved the staff’s ability to respond to their patients and families with empathy. The hospital collects quarterly patient satisfaction data using the Hospital Consumer Assessment of Healthcare Provider and Systems. In the third and fourth quarters of 2015, the unit’s patient satisfaction scores had declined significantly and remained low, in particular, the score for “how often did nurses listen carefully to you.” In February 2016, Empathy Huddles were implemented on the unit. Hospital Consumer Assessment of Healthcare Provider and Systems scores for this question were compared pre and post intervention. The top box response score was 46% preintervention (fourth quarter of 2015). After 2 quarters of Empathy Huddles, the top box score rose to 75% in the third quarter and 82% in the fourth quarter of 2016. The unit has maintained the top box score above 78%. In the fourth quarter of 2017, they achieved a top box score of 91%. Scores greater than 82% were sustained through the third quarter of 2018. Connecting was the overarching theme that emerged from interviews regarding Empathy Huddles. Interviewees described how Empathy Huddles helped them to connect empathetically with their patients, families, and each other. The huddles reminded staff to consider the day from the patients’ point of view and be mindful of their experiences.
Auditory Selective Attention Hindered by Visual Stimulus in Prelingually Deaf Children With Cochlear Implants
Authors: Chen Yuebo , Yue Zhenzhu , Liang Maojin , Liu Jinqun , Li Shao , Liu Jiahao , Zheng Yiqing
Published: April 2019

Objective:

To compare the influence of visual distractors on the performance of auditory selective attention between prelingually deaf children with a CI (cochlear implant) and children with normal-hearing.

Design:

Twenty-two patients who had a cochlear implant device (10 males and 12 females, aged 6.64 ± 0.99 yrs) and 16 normal-hearing children (6 males and 10 females, aged 6.09 ± 0.51 yrs) were recruited. Half of the auditory stimuli were presented together with visual stimuli, and participants were required to complete an auditory identification task. Reaction times and discriminability (d’) for these two groups were recorded and calculated.

Results:

The normal-hearing group had shorter mean reaction times than the CI group in detecting auditory targets. With visual distraction, the d’ of the normal-hearing group was significantly better than that of CI group (t = 2.649, p = 0.012), while no statistical significance was found between the two groups without visual distraction (t = 0.693, p = 0.493).

Conclusion:

Enhanced processing of visual stimuli interferes with auditory perception in CI users by occupying the capacity-limited attention.
Opting Out of a Time-of-Death Visit
Authors: Katzenberger Katherine S. , Nichols Michelle
Published: April 2019

Hospice patients die in various settings, including at home with family caregivers. Hospice offers a time-of-death visit to provide support and confirm death, a requirement in some states but not all. Few studies have been conducted among home hospice families exploring their experiences without a time-of-death visit. To better understand the family’s experience regarding the time of death of their loved one, we conducted an exploratory study using a hermeneutic phenomenological approach. Home hospice families who had experienced a death within the last 6 to 13 months and had not received a time-of-death visit were recruited. Seven interviews were conducted, and data were analyzed using an emergent thematic approach. Major themes included caregiver’s previous experience with death, caregiver support, final hours, and reasons for not selecting a time-of-death visit. Results showed families did well without a time-of-death visit when strong social support was present and conveyed the importance of allowing personal choice. Further research is needed to identify families in need of time-of-death visits and targeted support needs and to inform practice and policy guidelines.
Short-Stay Palliative Pain Management for Southwestern VA
Authors: Rumsey Christopher Michael
Published: April 2019

The increased demand for palliative care services has led to concerns surrounding workforce knowledge and resiliency, specifically with regard to palliative pain management for patients with life-limiting illnesses. Educational preparedness of nurses along with best processes and practices is necessary to promote optimal care for patients requiring palliative pain management. Through analyzing Veterans Administration Strategic Analytics for Improvement and Learning data, a deficiency in short-stay self-reported palliative patient pain management at the Southwestern Veterans Administration Medical Center, a level 1B, tertiary care referral center was defined. Best practices in the palliative care industry were then identified, and a quality improvement plan in the form of a nurse-driven palliative care pain education hands-on simulation was generated to promote excellence in care. Quality improvement for short-stay palliative pain management at the Southwestern Veterans Administration Medical Center was the end goal.
IgG4-positive Cell Quantification Distinguishes Between Inflammatory and Noninflammatory Diseases of the Orbit
Authors: Sweeney Adam R. , Keene Christopher D. , Cimino Patrick J. , Chang Shu-Hong
Published: April 2019

IgG4-related ophthalmic disease (IgG4-ROD) is a rare inflammatory disorder often refractory to corticosteroids and prone to recurrence. IgG4-ROD may frequently lack the characteristic histopathological features seen in other organs. Thus, the criteria for diagnosis of IgG4-ROD relies on elevated IgG4 cells seen on biopsied tissue. Proposed threshold levels of IgG4 to diagnose IgG4-ROD are currently based on a limited understanding of this cell type’s presence in the orbit. This study seeks to describe the population of IgG4 in inflammatory and noninflammatory orbital tissues. A tertiary care center’s pathology database was searched with keywords “orbit” or “orbital” from 1995 to 2013. Specimens meeting the selection criteria were evaluated, and regions of highest inflammation were identified and immunostained with IgG4 and CD138 antibodies. Immunohistochemical quantification proceeded as previously established by the international consensus criteria. Eighteen cases without a history of orbital inflammation were included as controls and were evaluated as above. Specimens from 68 inflammatory and 18 noninflammatory orbits met the selection criteria. Pathologist interreader correlation coefficient on quantification was >0.70 (P<0.001). The mean IgG4+/high powered field (HPF) and IgG4+/CD138 was 10.3 and 0.1 in inflammatory tissues and 0.5 and 0.01 in noninflammatory tissues, respectively. The spearman rho correlation coefficient between IgG4/HPF and IgG4+/CD138+ was >0.95 (P<0.0001). The mean IgG4/HPF in our study reached previously proposed threshold values for diagnosis of IgG4-ROD, illustrating the need for further discussion regarding diagnostic criteria of IgG4-ROD.
Long-Term Follow-Up of Infants After a Brief Resolved Unexplained Event–Related Hospitalization
Authors: Ari Anne , Atias Yifat , Amir Jacob
Published: April 2019

Objective

A brief resolved unexplained event (BRUE) in infancy is a common reason for visiting the emergency department. However, little is known about the long-term outcomes of such an event. This study evaluates future mortality, morbidity, and/or developmental outcome after a BRUE.

Methods

A single-center retrospective study performed in 2009 to 2013 included 87 hospitalized infants (<1 year old) fitting the American Academy of Pediatrics' criteria of a lower-risk BRUE, with 2 exceptions: no time limit to duration of episode and no age limit of ≥60 days. Hospitalized infants were followed up for up to 5 years via a telephone questionnaire to assess mortality rates, developmental delay, neurological/cardiovascular morbidity, and future hospitalizations.

Results

Most infants (94%) who experienced a BRUE were hospitalized before 6 months of age. No cases of mortality occurred. In terms of developmental outcome, 1 child (1.15%) was diagnosed as having a global developmental delay and 12 (13.7%) with a language delay, similar to prevalence rates by age in the United States. Three children (3.4%) were diagnosed as having an autism spectrum disorder, with higher prevalence rates than the global average. Simple febrile and nonfebrile seizures were seen at a rate similar to the general population. None of the children developed cardiovascular disease. Rehospitalization occurred in 22% of cases: 90% for common acute pediatric causes and 10% for recurrent choking events secondary to gastroesophageal reflux disease.

Conclusions

Low-risk hospitalized infants younger than 1 year who experienced a BRUE seem to generally have an excellent prognosis.
Effects of Elastic Therapeutic Taping on Joint Position Sense of the Ankle in Stroke Survivors
Authors: Mohammadi Roghayeh , Abdollahi Khorasgani Mojtaba , Tabatabaei Maryamasadat , Grampurohit Namrata
Published: April 2019

Impairments in ankle joint position sense along with muscle weakness greatly affect the recovery of balance among stroke survivors. Elastic therapeutic taping has been studied in musculoskeletal conditions of the ankle to improve joint position sense and its effects in stroke are not known. The aims of the study were to investigate the differences in joint position sense between paretic and nonparetic ankles and to examine the effects of elastic therapeutic taping on joint position sense of the paretic ankle in stroke survivors. Sixteen chronic stroke survivors participated in a 2-day protocol of ankle elastic therapeutic taping on the paretic side. Active and passive joint position sense at the ankle was measured by Biodex Isokinetic III system on both the paretic and nonparetic sides before elastic therapeutic taping and only the paretic side after elastic therapeutic taping. The active and passive ankle joint position sense values were significantly (P < 0.001) lower on the paretic side than the nonparetic side before intervention. Joint position sense significantly (P < 0.001) improved for the paretic ankle after elastic therapeutic taping. Chronic stroke survivors were deficient in ankle joint position sense on the paretic side. Elastic therapeutic taping was effective in the short term to improve active and passive joint position sense.
The Hispanic Paradox in Patients With Liver Cirrhosis: Current Evidence From a Large Regional Retrospective Cohort Study
Authors: Atiemo Kofi , Mazumder Nikhilesh R. , Caicedo Juan C. , Ganger Daniel , Gordon Elisa , Montag Samantha , Maddur Haripriya , VanWagner Lisa B. , Goel Satyender , Kho Abel , Abecassis Michael , Zhao Lihui , Ladner Daniela
Published: April 2019

Background.

Despite lower socioeconomic status, Hispanics in the United States paradoxically maintain equal or higher average survival rates compared to non-Hispanic Whites (NHW).

Methods.

We used multivariable Cox regression to assess whether this “Hispanic paradox” applies to patients with liver cirrhosis using a retrospective cohort of twenty 121 patients in a Chicago-wide electronic health record database.

Results.

Our study population included 3279 (16%) Hispanics, 9150 (45%) NHW, 4432 (22%) African Americans, 529 (3%) Asians, and 2731 (14%) of other races/ethnic groups. Compared to Hispanics, NHW (hazard ratio [HR] 1.26; 95% confidence interval [CI], 1.16-1.37), African American (HR 1.26; 95% CI, 1.15-1.39), and other races/ethnic groups (HR 1.55; 95% CI, 1.40-1.71) had an increased risk of death despite adjustment for age, sex, insurance status, etiology of cirrhosis, and comorbidities. On stratified analyses, a mortality advantage for Hispanics compared to NHW was seen for alcohol cirrhosis (HR for NHW 1.35; 95% CI, 1.19-1.52), hepatitis B (HR for NHW 1.35; 95% CI, 0.98-1.87), hepatitis C (HR for NHW 1.21; 95% CI, 1.06-1.38), and nonalcoholic steatohepatitis (HR for NHW 1.14; 95% CI, 0.94-1.39). There was no advantage associated with Hispanic race over NHW in cases of hepatocellular carcinoma or cholestatic liver disease.

Conclusions.

Hispanic patients with cirrhosis experience a survival advantage over many other racial groups despite adjustment for multiple covariates.
Towards a multi-level and a multi-disciplinary approach to DNA oncovirus virulence
Authors: Alizon Samuel , Bravo Ignacio G. , Farrell Paul J. , Roberts Sally
Published: April 2019

One out of 10 cancers is estimated to arise from infections by a handful of oncogenic viruses. These infectious cancers constitute an opportunity for primary prevention through immunization against the viral infection, for early screening through molecular detection of the infectious agent, and potentially for specific treatments, by targeting the virus as a marker of cancer cells. Accomplishing these objectives will require a detailed understanding of the natural history of infections, the mechanisms by which the viruses contribute to disease, the mutual adaptation of viruses and hosts, and the possible viral evolution in the absence and in the presence of the public health interventions conceived to target them. This issue showcases the current developments in experimental tissue-like and animal systems, mathematical models and evolutionary approaches to understand DNA oncoviruses. Our global aim is to provide proximate explanations to the present-day interface and interactions between virus and host, as well as ultimate explanations about the adaptive value of these interactions and about the evolutionary pathways that have led to the current malignant phenotype of oncoviral infections.

This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.
Androgen-dmrt1positive feedback programs the rice field eel (Monopterus albus) sex transdifferentiation
Authors: Wen Bin , Qu Xiancheng , Pan Lisha , Gao Jianzhong , Wu Haowei , Wang Qian
Published: April 2019

The rice field eelMonopterus albusis a hermaphroditic protogynous fish species that undergoes sex reversal from female to male. However, the potential mechanisms underlying the process of sex transformation are still unclear. We analyzed and compared the gene sequence ofM. albus dmrt15′ upstream region and its potential transcription factor binding sites with other known species and examined thein vitroeffects of testosterone (T) on the expression levels ofdmrt1aandfoxl2in the ovotestis. Moreover, we cloned and analyzed the expression of genes encoding enzymes, 11β-hydroxylase (11β-h) and 11β-hydroxysteroid dehydrogenase (11β-hsd), involved in the production of 11-ketotestosterone (11-KT). The results showed that, compared with other fish species,M. albus dmrt15′ upstream region contained unique androgen response elements (AREs) with one on the sense strand and the other one on the antisense strand, indicating a crucial role for androgens in the transcriptional regulation ofdmrt1. The expression ofdmrt1awas induced but the expression offoxl2was inhibited by T manipulationin vitro, suggesting that blood androgen could activate the transcription ofdmrt1in the ovotestis. Moreover, the expression levels of11β-hand11β-hsd2were predominantly expressed in testis, much less in ovotestis, and barely in ovary, suggesting the production of 11-KT during sex reversal. Androgens are synthesized in large amounts during sex reversal, leading to the promotion ofdmrt1transcription, and thus, gonadal somatic cells transdifferetiation. Overall, androgen-dmrt1positive feedback programs theM. albussex reversal.
Fine-scale ecological and transcriptomic data reveal niche differentiation of an allopolyploid from diploid parents in Cardamine
Authors: Akiyama Reiko , Sun Jianqiang , Hatakeyama Masaomi , Lischer Heidi E.L. , Briskine Roman V. , Hay Angela , Gan Xiangchao , Tsiantis Miltos , Kudoh Hiroshi , Kanaoka Masahiro M. , Sese Jun , Shimizu Kentaro K. , Shimizu-Inatsugi Rie
Published: April 2019

Polyploidization, or whole genome duplication, is one of the major mechanisms of plant speciation. Allopolyploids (species that harbor polyploid genomes originating from hybridization of different diploid species) have been hypothesized to occupy a niche with intermediate, broader, or fluctuating environmental conditions compared with parental diploids. It remains unclear whether empirical data support this hypothesis and whether specialization of expression patterns of the homeologs (paralogous gene copies resulting from allopolyploidization) relates to habitat environments. Here, we studied the ecology and transcriptomics of a wild allopolyploid Cardamine flexuosa and its diploid parents C. hirsuta and C. amara at a fine geographical scale in their native area in Switzerland. We found that the diploid parents favored opposite extremes in terms of soil moisture, soil carbon-to-nitrogen ratios, and light availability. The habitat of the allopolyploid C. flexuosa was broader compared with those of its parental species and overlapped with those of the parents, but not at its extremes. In C. flexuosa, the genes related to water availability were overrepresented among those at both the expression level and the expression ratio of homeolog pairs, which varied among habitat environments. These findings provide empirical evidence for niche differentiation between an allopolyploid and its diploid parents at a fine scale, where both ecological and transcriptomic data indicated water availability to be the key environmental factor for niche differentiation.

Significance statement

Polyploidization, or whole genome duplication, is common in plants and may contribute to their ecological diversification. However, little is known about the niche differentiation of wild allopolyploids relative to their diploid parents and the gene expression patterns that may underlie such ecological divergence. We detected niche differentiation between the allopolyploid Cardamine flexuosa and its diploid parents C. amara and C. hirsuta along water availability gradient at a fine scale. The ecological differentiation was mirrored by the dynamic control of water availability-related gene expression patterns according to habitat environments. Thus, both ecological and transcriptomic data revealed niche differentiation between an allopolyploid species and its diploid parents.
Dopamine depletion affects vocal acoustics and disrupts sensorimotor adaptation in songbirds
Authors: Saravanan Varun , Hoffmann Lukas A , Jacob Amanda L , Berman Gordon J , Sober Samuel J
Published: April 2019

Dopamine is hypothesized to convey important error information in reinforcement learning tasks with explicit appetitive or aversive cues. However, during motor skill learning the only available feedback signal is typically an animal’s evaluation of the sensory feedback arising from its own behavior, rather than any external reward or punishment. It has previously been shown that intact dopaminergic signaling from the ventral tegmental area – substantia nigra compacta complex (VTA/SNc) is necessary for vocal learning in response to an external aversive auditory cue in songbirds. However, the role of dopamine in learning in the absence of explicit external cues is still unclear. Here we used male Bengalese finches (Lonchura striatavar.domestica) to test the hypothesis that dopamine signaling is necessary for self-evaluation driven sensorimotor learning. We combined 6-hydroxydopamine (6-OHDA) lesions of dopaminergic terminals within Area X, a songbird basal ganglia nucleus critical for vocal learning, with a headphones learning paradigm that shifted the birds’ auditory feedback and compared their learning to birds without lesions. We found that 6-OHDA lesions affected song behavior in two ways. First, over a period of days lesioned birds systemically lowered their pitch regardless of the presence or absence of auditory errors. Second, 6-OHDA lesioned birds also displayed severe deficits in sensorimotor learning as measured by their adaptive change in pitch in response to the pitch-shifted auditory error. Our results suggest roles for dopamine both in motor production and in auditory error processing during vocal learning.

Significance Statement

Dopamine has been hypothesized to convey a reward prediction error signal in learning tasks involving external reinforcement. However the role dopamine plays in tasks involving self-guided error correction in the absence of external reinforcement is much less clear. To address this question, we studied the role of dopamine in sensorimotor adaptation using male Bengalese finches, which spontaneously produce a complex motor behavior (song) and are capable of modulating their behavioral output in response to induced auditory errors. Our results reveal that in addition to conveying errors in motor performance, dopamine may also have a role in modulating effort and in choosing a corrective response to the auditory error.
Cas12a trans-cleavage can be modulated in vitro and is active on ssDNA, dsDNA, and RNA
Authors: Fuchs Ryan T. , Curcuru Jennifer , Mabuchi Megumu , Yourik Paul , Robb G. Brett
Published: April 2019

CRISPR-Cas12a (Cpf1) are RNA-guided nuclease effectors of acquired immune response that act in their native organisms by cleaving targeted DNA sequences. Like CRISPR-Cas9 RNA-guided DNA targeting enzymes, Cas12a orthologs have been repurposed for genome editing in non-native organisms and for DNA manipulationin vitro. Recent studies have shown that activation of Cas12a via guide RNA-target DNA pairing causes multiple turnover, non-specific ssDNA degradation intrans, after single turnover on-target cleavage incis. We find that the non-specifictransnuclease activity affects RNA and dsDNA in addition to ssDNA, an activity made more evident by adjustment of reaction buffer composition. The magnitude of thetransnuclease activity varies depending on features of the guide RNA being used, specifically target sequence composition and length. We also find that the magnitude oftransnuclease activity varies between the three most well-studied Cas12a orthologs and that the Cas12a fromLachnospiraceaebacterium ND2006 appears to be the most active.
Accelerated evolution of oligodendrocytes in human brain
Authors: Berto Stefano , Mendizabal Isabel , Usui Noriyoshi , Toriumi Kazuya , Chatterjee Paramita , Douglas Connor , Tamminga Carol , Preuss Todd M. , Yi Soojin V. , Konopka Genevieve
Published: April 2019

Recent discussions of human brain evolution have largely focused on increased neuron numbers and changes in their connectivity and expression. However, it is increasingly appreciated that oligodendrocytes play important roles in cognitive function and disease. Whether both cell-types follow similar or distinctive evolutionary trajectories is not known. We examined the transcriptomes of neurons and oligodendrocytes in the frontal cortex of humans, chimpanzees, and rhesus macaques. We identified human-specific trajectories of gene expression in neurons and oligodendrocytes and show that both cell-types exhibit human-specific upregulation. Moreover, oligodendrocytes have undergone accelerated gene expression evolution in the human lineage compared to neurons. The signature of acceleration is enriched for cell type-specific expression alterations in schizophrenia. These results underscore the importance of oligodendrocytes in human brain evolution.
Distinctions among real and apparent respiratory motions in human fMRI data
Authors: Power Jonathan D. , Silver Benjamin M. , Dubin Marc J. , Martin Alex , Jones Rebecca M.
Published: April 2019

Head motion estimates in functional magnetic resonance imaging (fMRI) scans appear qualitatively different with sub-second image sampling rates compared to the multi-second sampling rates common in the past. Whereas formerly the head appeared still for much of a scan with brief excursions from baseline, the head now appears to be in constant motion, and motion estimates often seem to divulge little information about what is happening in a scan. This constant motion has been attributed to respiratory oscillations that do not alias at faster sampling rates, and investigators are divided on the extent to which such motion is “real” motion or only “apparent” pseudomotion. Some investigators have abandoned the use of motion estimates entirely due to these considerations. Here we investigate the properties of motion in several fMRI datasets sampled at rates between 720-1160 ms, and describe 5 distinct kinds of respiratory motion: 1) constant real respiratory motion in the form of head nodding most evident in vertical position and pitch, which can be very large; 2) constant pseudomotion at the same respiratory rate as real motion, occurring only in the phase encode direction; 3) punctate real motions occurring at times of very deep breaths; 4) a low-frequency pseudomotion in only the phase encode direction following very deep breaths; 5) slow modulation of vertical and anterior-posterior head position by the respiratory envelope. We reformulate motion estimates in light of these considerations and obtain good concordance between motion estimates, physiologic records, image quality measures, and events evident in the fMRI signals.

Highlights

- Examines several fast-TR datasets with sampling rates of 720-1160 ms

- Identifies 7 kinds of motion in fMRI scans, 5 of them related to respiration

- Identifies 2 forms of pseudomotion occurring only in phase encode direction

- Pseudomotion is a function of soft tissue mass, not lung volume

- Reformulates motion estimates to draw out particular kinds of motion
Identification of a basal stem cell subpopulation in the prostate via functional, lineage tracing and single-cell RNA-seq analyses
Authors: Wang Xue , Xu Haibo , Cheng Chaping , Ji Zhongzhong , Zhao Huifang , Sheng Yaru , Li Xiaoxia , Wang Jinming , Shu Yu , He Yuman , Fan Liancheng , Dong Baijun , Xue Wei , Chua Chee Wai , Wu Dongdong , Gao Wei-Qiang , Zhu Helen He
Published: April 2019

The basal cell compartment in many epithelial tissues such as the prostate, bladder, and mammary gland are generally believed to serve as an important pool of stem cells. However, basal cells are heterogenous and the stem cell subpopulation within basal cells is not well elucidated. Here we uncover that the core epithelial-to-mesenchymal transition (EMT) inducer Zeb is exclusively expressed in a prostate basal cell subpopulation based on both immunocytochemical and cell lineage tracing analysis. The Zeb1+prostate epithelial cells are multipotent prostate basal stem cells (PBSCs) that can self-renew and generate functional prostatic glandular structures with all three epithelial cell types at the single-cell level. Genetic ablation studies reveal an indispensable role for Zeb1 in prostate basal cell development. Utilizing unbiased single cell transcriptomic analysis of over 9000 mouse prostate basal cells, we find that Zeb1+basal cell subset shares gene expression signatures with both epithelial and mesenchymal cells and stands out uniquely among all the basal cell clusters. Moreover, Zeb1+epithelial cells can be detected in mouse and clinical samples of prostate tumors. Identification of the PBSC and its transcriptome profile is crucial to advance our understanding of prostate development and tumorigenesis.
A Theoretical Model of Telomere Length Regulation
Authors: Ishii Haruhiko
Published: April 2019

Telomere length is maintained by a negative feedback mechanism that inhibits the telomerase activity when the telomere is sufficiently long. A prevailing explanation is that the negative feedback is caused by a mechanism that “counts” the number of regulatory protein molecules that are bound to the telomere. However, how such protein counting is accomplished is not clear. In this paper, I introduce a simple theoretical model to consider how the telomerase inhibition can depend on the telomere length. I show that this model is able to explain some key features of regulation of telomere length. While the real telomeres are more complex, this simple model may capture the essence of the mechanism.
KofamKOALA: KEGG ortholog assignment based on profile HMM and adaptive score threshold
Authors: Aramaki Takuya , Blanc-Mathieu Romain , Endo Hisashi , Ohkubo Koichi , Kanehisa Minoru , Goto Susumu , Ogata Hiroyuki
Published: April 2019

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

Availability

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

Contact

ogata@kuicr.kyoto-u.ac.jp
A Comprehensive Molecular Portrait of Human Urine-derived Renal Progenitor Cells
Authors: Rahman Md Shaifur , Wruck Wasco , Spitzhorn Lucas-Sebastian , Bohndorf Martina , Martins Soraia , Asar Fatima , Ncube Audrey , Erichsen Lars , Graffmann Nina , Adjaye James
Published: April 2019

Background

Human urine is now recognised as a non-invasive source of stem cells with regeneration potential. These cells are mesenchymal stem cells but their detailed molecular and cellular identities are poorly defined. Furthermore, unlike the mouse, the gene regulatory network driving self-renewal and differentiation into functional renal cellsin vitroremain unresolved.

Methods

We isolated urine stem cells from 10 individuals from both genders and distinct ages, characterized them as renal progenitor cells and explored the gene regulatory network sustaining self-renewal.

Results

These cells express pluripotency-associated proteins-TRA-1-60, TRA-1-81, SSEA4, C-KIT and CD133. Expression of pluripotency-associated proteins enabled rapid reprogramming into iPSCs using episomal-based plasmids without pathway perturbations. Transcriptome analysis revealed expression of a plethora of nephrogenesis-related genes such asSIX2, OSR1, CITED1, NPHS2, NPHS1, PAX2, SALL1, AQP2, EYA1, SLC12A1andUMOD. As expected, the cells transport Albumin by endocytosis. Based on this, we refer to these cells as urine derived renal progenitor cells-UdRPCs. Associated GO-term analysis of UdRPCs and UdRPC-iPSCs underlined their renal identity and functionality. Upon differentiation by WNT activation using the GSK3β-inhibitor (CHIR99021), transcriptome and KEGG pathway analysis revealed upregulation of WNT-associated genes-AXIN2, JUN and NKD1.Protein interaction network identified JUN- a downstream target of the WNT pathway in association with STAT3, ATF2 and MAPK1 as a putative regulator of self-renewal and differentiation in UdRPCs. Furthermore, like pluripotent stem cells, self-renewal is maintained by FGF2-driven TGFβ-SMAD2/3 pathway.

Conclusion

Thisin vitromodel and the data presented should lay the foundation for studying nephrogenesis in man.

Significance Statement

Human urine is a non-invasive source of stem cells with regeneration potential. Here, we investigated the cellular and molecular identities, and the gene regulation driving self-renewal and differentiation of these cellsin vitro. These cells express pluripotency-associated markers enabling easy reprogramming. Based on the expression of renal associated genes, proteins and functionality, we refer to these cells as urine derived renal progenitor cells-UdRPCs. CHIR99021-induced differentiation of UdRPCs activated WNT-related genes-AXIN2, JUN and NKD1.Protein interaction network identified JUN as a putative regulator of differentiation whereas self-renewal is maintained by FGF2-driven TGFβ-SMAD2/3. Our data will enhance understanding of the molecular identities of UdRPCs, and enable the generation of renal disease modelsin vitroand eventually kidney-associated regenerative therapies.
The design of novel metronidazole benzoate structures: exploring stoichiometric diversity
Authors: Santiago de Oliveira Yara , Saraiva Costa Wendell , Ferreira Borges Poliana , Silmara Alves de Santana Maria , Ayala Alejandro Pedro
Published: April 2019

The use of supramolecular synthons as a strategy to control crystalline structure is a crucial factor in developing new solid forms with physicochemical properties optimized by design. However, to achieve this objective, it is necessary to understand the intermolecular interactions in the context of crystal packing. The feasibility of a given synthon depends on its flexibility to combine the drug with a variety of coformers. In the present work, the imidazole–hydroxy synthon is investigated using as the target molecule benzoylmetronidazole [BZMD; systematic name 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl benzoate], whose imidazole group seems to be a suitable acceptor for hydrogen bonds. Thus, coformers with carboxylic acid and phenol groups were chosen. According to the availability of binding sites presented in the coformer, and considering the proposed synthon and hydrogen-bond complementarity as major factors, different drug–coformer stoichiometric ratios were explored (1:1, 2:1 and 3:1). Thirteen new solid forms (two salts and eleven cocrystals) were produced, namely BZMD–benzoic acid (1/1), C13H13N3O4·C7H6O2, BZMD–β-naphthol (1/1), C13H13N3O4·C10H8O, BZMD–4-methoxybenzoic acid (1/1), C13H13N3O4·C8H8O3, BZMD–3,5-dinitrobenzoic acid (1/1), C13H13N3O4·C7H4N2O6, BZMD–3-aminobenzoic acid (1/1), C13H13N3O4·C7H7NO2, BZMD–salicylic acid (1/1), C13H13N3O4·C7H6O3, BZMD–maleic acid (1/1) {as the salt 1-[2-(benzoyloxy)ethyl]-2-methyl-5-nitro-1H-imidazol-3-ium 3-carboxyprop-2-enoate}, C13H14N3O4
+·C4H3O4
−, BZMD–isophthalic acid (1/1), C13H13N3O4·C8H6O4, BZMD–resorcinol (2/1), 2C13H13N3O4·C6H6O2, BZMD–fumaric acid (2/1), C13H13N3O4·0.5C4H4O4, BZMD–malonic acid (2/1), 2C13H13N3O4·C3H2O4, BZMD–2,6-dihydroxybenzoic acid (1/1) {as the salt 1-[2-(benzoyloxy)ethyl]-2-methyl-5-nitro-1H-imidazol-3-ium 2,6-dihydroxybenzoate}, C13H14N3O4
+·C7H5O4
−, and BZMD–3,5-dihydroxybenzoic acid (3/1), 3C13H13N3O4·C7H6O4, and their crystalline structures elucidated, confirming the robustness of the selected synthon.
A triangular palladium(II) supramolecular coordination complex based on 1,4-bis(1H-imidazol-1-yl)benzene and (2,2′-bipyridyl)palladium(II) nitrate: synthesis and crystal structure
Authors: Daran Jean-Claude , Gimeno Nicolas , Gouygou Maryse , Volkman Jérôme
Published: April 2019

The self-assembly of ditopic bis(1H-imidazol-1-yl)benzene ligands (L
H) and the complex (2,2′-bipyridyl-κ2
N,N′)bis(nitrato-κO)palladium(II) affords the supramolecular coordination complex tris[μ-bis(1H-imidazol-1-yl)benzene-κ2
N
3:N
3′]-triangulo-tris[(2,2′-bipyridyl-κ2
N,N′)palladium(II)] hexakis(hexafluoridophosphate) acetonitrile heptasolvate, [Pd3(C10H8N2)3(C12H10N4)3](PF6)6·7CH3CN, 2. The structure of 2 was characterized in acetonitrile-d
3 by 1H/13C NMR spectroscopy and a DOSY experiment. The trimeric nature of supramolecular coordination complex 2 in solution was ascertained by cold spray ionization mass spectrometry (CSI–MS) and confirmed in the solid state by X-ray structure analysis. The asymmetric unit of 2 comprises the trimetallic Pd complex, six PF6
− counter-ions and seven acetonitrile solvent molecules. Moreover, there is one cavity within the unit cell which could contain diethyl ether solvent molecules, as suggested by the crystallization process. The packing is stabilized by weak inter- and intramolecular C—H...N and C—H...F interactions. Interestingly, the crystal structure displays two distinct conformations for the L
H ligand (i.e. syn and anti), with an all-syn-[Pd] coordination mode. This result is in contrast to the solution behaviour, where multiple structures with syn/anti-L
H and syn/anti-[Pd] are a priori possible and expected to be in rapid equilibrium.
Financial services and ethical hazards: antecedents of repeated ethical violation
Authors: Cheng Chia-Yi , Ho Tzu-Ping
Published: April 2019

Purpose

Prior studies have extensively explored individual examples of unethical behavior in sales organizations but focused little on repeated violation (RV) of ethical codes, particularly when managers develop salesforces. Based on social learning theory (SLT), the authors propose a multilevel model of RV antecedents and suggest that organizational influence (social cues and modeling) and individual factors (observer characteristics and behavioral outcomes) affect RV, especially with increasing recruitment of salespeople.

Design/methodology/approach

Using data from a leading financial company in Taiwan, the authors analyzed 1,231 records of salespeople’s misbehavior through logistic regression and average marginal effects.

Findings

Modeling in the organization (i.e. peer misconduct), observer characteristics (i.e. experience concerning job tenure and prior violations) and behavioral outcomes (i.e. information concealment violations) were all found to affect the likelihood of RV, and the interactional effect of organizational size was confirmed.

Research limitations/implications

This study contributes to ethical decision-making theory by explaining aspects of RV through SLT. Its multilevel model, integrated with organizational strategy theories, adds an SLT-focused paradigm into unethical behavior research by considering vicarious learning and self-learning, alongside the reciprocal determinism of cognition, behavior, and environment.

Practical implications

Managers should consider socially based patterns of violation when initiating a sales business plan. The chances of RV are increased by unethical models in the organization and offenders’ potential for violations, which is reinforced by social environment.

Originality/value

This study clarified the key drivers of RV decision-making using SLT and identified an effective sales development strategy to maintain an ethically responsible salesforce.
The effect of others’ outcome valence on spontaneous gift-giving behavior
Authors: Hwang Jaewon , Chu Wujin
Published: April 2019

Purpose

In social networking services gift giving, the decision to send a gift is often initiated by spontaneous news about others, who may have recently experienced fortune or misfortune. The purpose of this paper is to show that the valence of the other’s event can affect the empathy experienced by the giver and that the level of empathy affects gift selection behavior.

Design/methodology/approach

Study 1 investigated the relationship between empathy and valence of other’s event and the underlying mechanism of changes in self-esteem. Study 2 explored how different levels of empathies lead to different gift selection behavior. Study 3 replicated the results of Study 2 using a different measurement approach.

Findings

Across the three studies, findings consistently suggest that the empathy arising from unexpected news of the others’ fortune was lower compared to that of the others’ misfortune because of threats to self-esteem. In addition, greater empathy prompted gift givers to spend more time and effort in gift selection.

Practical implications

Understanding how valence of event experienced by others might motivate givers to engage in selecting a gift online can help retailers increase predictive insights for recommendations.

Originality/value

While past research focused on ritual gift giving, this research examined spontaneous gift giving. The study is also unique in that the empathy gap between the giver and the receiver is a result of the changes in the psychological state of the giver.
Adoption of e-government services by small municipalities
Authors: Chen Yu-Che , Kim Yunseung
Published: April 2019

Purpose

The purpose of this paper is to fill the research gap in online information and service adoption by small public organizations. According to the US Census, small municipalities with populations of 5,000 or less constitute 76 percent of all municipalities. Moreover, although these governments can benefit most from e-government adoption, their e-government activities are rarely studied.

Design/methodology/approach

The primary data collection is a state-wide survey of small municipalities along with collecting data on websites and other government documents. The data analysis utilized logistic regression for adoption decisions.

Findings

The findings suggest a distinct set of factors influencing e-government adoption by small municipalities as opposed to large ones. Moreover, management support for open access to government is critical for both e-government information and transaction services while transaction services are also driven by administrative capacity and citizen demand.

Originality/value

This study is original in several ways. First, it is comprehensive in incorporating capacity and network factors along with motivation for management support. Second, it focuses on small municipalities that are important but less studied. At last, it provides a rich understanding of the distinction between information and transaction e-government services.
Technology application and police management: issues and challenges
Authors: Liou Kuotsai Tom
Published: April 2019

Purpose

The purpose of this paper is to examine critical issues and challenges that are related to the application of technology to improve the management of police organizations.

Design/methodology/approach

First, the study reviews the background of the police service model, the development of police-related technology and the relationship between these technologies and police performance measures. Based on the analysis of managerial concepts, the study provides discussions about risks of technology and human factors, resource limitation, professional attitude and culture, privacy concerns, citizen video and social media, and public trust.

Findings

The study concludes with suggestions to examine police technology application from a broad perspective to address not only technology operational issues but also related organization, management, community and policy concerns.

Originality/value

Findings of this study contribute to the understanding of technology application, contribution and limitation in public management.