bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Feasibility of a Spanish Language Version of the Tobacco, Alcohol, Prescription Drug, and Illicit Substance Use (TAPS) Tool
Authors: Sanchez Katherine , Gryczynski Jan , Carswell Steven B. , Schwartz Robert P.
Published: July 2020

Objectives:

The Tobacco, Alcohol, Prescription drug, and illicit Substance use (TAPS) Tool is a validated two-stage screening and brief assessment in primary care for unhealthy substance use. We developed a Spanish language version of the TAPS Tool and conducted a small study of its feasibility, acceptability, and preliminary validity.

Methods:

Participants were adult primary care patients ages 18 or older with Spanish as their primary language (N = 10 for development/refinement using qualitative congnitive interviewing; N = 100 for the preliminary validation study). The Spanish language TAPS Tool was administered in both interviewer- and selfadministered tablet format (in random order). We examined disclosure of substance use on the TAPS by administration format, and compared it with established measures for identifying substance use and substance use disorders.

Results:

The Spanish language TAPS was feasible to use and participants reported high levels of acceptability. The rates of past 12-month substance use were 11% for tobacco, 28% for risky alcohol, 4% for illicit drugs, 1% for nonmedical prescription drugs and substance use disorders rates were 7% for tobacco, 2% for alcohol, and 1% for other substances. The selfadministered TAPS elicited 1, 3, and 1 additional disclosures of tobacco, risky, alcohol, and marijuana use than the interviewer-administered TAPS, respectively. Rates of disclosure on the TAPS were similar to those on established measures for past 12-month and 3-month time frames.

Conclusions:

The current study represents a starting point for expanding the availability of the TAPS Tool beyond its original English language version into Spanish. The Spanish language TAPS Tool could expand options for substance use screening in primary care settings with Spanish-dominant/preferred populations.

Trial registration:

The studies were registered with www.clinicaltrials.gov: NCT03879785, March 19, 2019.
LncRNA MEG8 promotes tumor progression of non-small cell lung cancer via regulating miR-107/CDK6 axis
Authors: Liu Ying , Li Lei , Shang Peng , Song Xiang
Published: July 2020

Mounting evidence has implicated the vital role of long noncoding RNAs (lncRNAs) in non-small cell lung cancer (NSCLC). This study aims to investigate the mechanism of lncRNA MEG8 on NSCLC progression. The mRNA expressions of MEG8 and miR-107 were examined in tumor and adjacent normal tissues from patients with NSCLC by qRT-PCR. Lung epithelial BEAS-2B cells were transfected with MEG8 overexpression plasmid, and NSCLC A549 and H1299 cells were transfected with MEG8 or miR-107 overexpression/knockdown plasmid to detect the function of MEG8 or miR-107 on cell activity. The function of MEG8 and miR-107 on cell proliferation, cell cycle changes, invasion and migration was separately determined by Cell counting kit-8 assay and 5-ethynyl-2’-deoxyuridine staining, flow cytometry, transwell and cell scratch test. Target sites for miR-107 and MEG8, miR-107 and CDK6 were determined and verified by a dual luciferase gene reporter assay. The expression levels of the Rb/E2F3 signal pathway related proteins (p21, p27, E2F3 and Rb) were inspected by Western blot. MEG8 was strongly expressed while miR-107 was lowly expressed in tumor tissues and cells. Overexpression of MEG8 potentiated cell proliferation, migration and invasion in BEAS-2B cells. Silencing MEG8 or overexpression of miR-107 clearly hindered cell progression in A549 and H1299 cells. Mechanistically, MEG8 and CDK6 can competitively bind to miR-107 and together regulate the progression of NSCLC. Additionally, silencing MEG8 or overexpression of miR-107 can inhibit the phosphorylation levels of Rb and E2F3. Evidence in this work indicated that MEG8 regulates miR-107/CDK6 axis to promote NSCLC progression by activating the Rb/E2F3 pathway.
Sequential habituation to space, object and stranger is differentially modulated by glutamatergic, cholinergic and dopaminergic transmission
Authors: Yeap Jie , Crouch Barry , Riedel Gernot , Platt Bettina
Published: July 2020

Novel object and social interaction tasks allow assessments of rodent cognition and social behavior. Here, we combined these tasks and defined unequivocal locations of interest. Our procedure, termed OF-NO-SI, comprised habituation to the open field (OF), novel object (NO) and social interaction (SI) stages. Habituation was measured within- and between-trials (10 minutes each, two per stage). Ambulation emerged as the appropriate proxy during the OF stage, but NO and SI trials were best quantified via direct exploration measures. We pharmacologically validated the paradigm using 5-month old C57BL/6J male mice, treated intraperitoneally with (1) 0.5 mg/kg scopolamine, (2) 0.05 mg/kg MK-801 and (3) 0.05 mg/kg SCH-23390 to block muscarinic (M1), NMDA, and D1 receptors, respectively, or (4) vehicle (distilled water). Activity and gross exploratory behavior were affected by all compounds cf. vehicle: scopolamine and MK-801 cohorts were hyperactive, while SCH-23390 caused hypo-locomotion throughout. Vehicle treated mice showed reliable habituation to all stages for time in interaction zone, directed exploration and number of visits. Exploration was severely impaired by scopolamine. MK-801 mostly affected within-session exploration but also increased exploration of the conspecific compared to the object. Interestingly, even though within-trial habituation was lacking in the SCH-23390 cohort, between-trial habituation was largely intact, despite reduced locomotion. Our data suggest that the OF-NO-SI task is a convenient and robust paradigm to measure habituation to different experimental settings and stimuli. It allows the dissociation of proxies related to activity and non-associative learning/memory, as revealed by distinct pharmacological treatment effects within- vs. between-trials.
Management of the Category II Fetal Heart Rate Tracing
Authors: ELLER ALEXANDRA G. , ESPLIN M. SEAN
Published: July 2020

Management of the category II fetal heart rate (FHR) tracing presents a common challenge in obstetrics. Up to 80% of women will have a category II FHR tracing at some point during labor. Here we propose a management algorithm to identify specific features of the FHR tracing that correlate with risk for fetal acidemia, target interventions to address FHR decelerations, and guide clinicians about when to proceed toward operative vaginal delivery or cesarean to achieve delivery before there is a high risk for significant fetal acidemia with potential for neurological injury or death.
Targeting multiple domains of residual cardiovascular disease risk in patients with diabetes
Authors: Patel Kershaw V. , Vaduganathan Muthiah
Published: July 2020

Purpose of review

There has been a recent resurgence of diabetes-related cardiovascular complications after years of steady improvement. This review highlights established and emerging contemporary secondary prevention approaches that lower the risk of atherosclerotic and nonatherosclerotic cardiovascular disease events among patients with diabetes.

Recent findings

Secondary prevention therapies modify residual risk targets, including cardiometabolic pathways, lipoproteins, thrombosis, and inflammation. Large-scale clinical trials of sodium-glucose cotransporter-2 inhibitors have demonstrated significant reductions in hospitalization for heart failure. Glucagon-like peptide-1 receptor agonists have reduced the risk of major adverse cardiovascular events. Recent clinical trials provide evidence supporting the use of nonstatin lipid-lowering therapies, novel antiplatelet and anticoagulant strategies, and antiinflammatory strategies in select cases.

Therapeutic approaches targeting multiple distinct pathways have been shown to improve cardiometabolic risk in diabetes. Individual patient characteristics and consideration of residual risk targets may help guide selection of comprehensive secondary prevention approaches.
Isolated systolic hypertension and 29-year cardiovascular mortality risk in Japanese adults aged 30--49 years
Authors: Hisamatsu Takashi , Miura Katsuyuki , Ohkubo Takayoshi , Kadota Aya , Kondo Keiko , Kita Yoshikuni , Hayakawa Takehito , Kanda Hideyuki , Okamura Tomonori , Okayama Akira , Ueshima Hirotsugu
Published: July 2020

Objective:

The prognostic implication of isolated systolic hypertension (ISH), defined as SBP at least 140 mmHg and DBP less than 90 mmHg, among young-to-middle-aged adults remains controversial. We examined the association of ISH with cardiovascular disease (CVD) risk in adults aged 30–49 years.

Methods:

In a prospective cohort of representative Japanese general populations from the NIPPON DATA80 (1980–2009), we studied 4776 participants (mean age, 39.4 years; 55.4% women) without clinical CVD or antihypertensive medication. Participants were classified as follows: normal blood pressure (BP) (SBP/DBP, <120/<80 mmHg), high-normal BP (120–129/<80 mmHg), elevated BP (130–139/80–89 mmHg), ISH, isolated diastolic hypertension (IDH) (<140/≥90 mmHg), and systolic--diastolic hypertension (SDH) (≥140/≥90 mmHg).

Results:

ISH was observed in 389 (8.1%) participants. During the 29-year follow-up, 115 participants died of CVD, 28 of coronary heart disease, and 49 of stroke. Cox proportional hazards models adjusted for demographics and CVD risk factors showed that participants with ISH had higher risk of CVD mortality than those with normal BP [hazard ratio (confidence interval), 4.10 (1.87–9.03)]. The magnitude of CVD mortality risk related to ISH was comparable with that related to IDH [3.38 (1.31–8.72)] and not as great as that related to SDH [5.41 (2.63–11.14)]. We found significant associations of ISH with coronary and stroke mortality. The association of ISH with CVD mortality was consistent across men and women and those aged 30–39 and 40–49 years.

Conclusion:

ISH among young-to-middle-aged Japanese adults was independently associated with higher risk of CVD mortality later in life.
The Impact of Coronavirus Disease 2019 Pandemic on U.S. and Canadian PICUs
Authors: Sachdeva Ramesh , Rice Tom B. , Reisner Brian , Brundage Nancy , Hulbert Cheryl , Kaminski Alex , Wetzel Randall C.
Published: July 2020

Objectives:

There are limited reports of the impact of the coronavirus disease 2019 pandemic focused on U.S. and Canadian PICUs. This hypothesis-generating report aims to identify the United States and Canadian trends of coronavirus disease 2019 in PICUs.

Design and Setting:

To better understand how the coronavirus disease 2019 pandemic was affecting U.S. and Canadian PICUs, an open voluntary daily data collection process of Canadian and U.S. PICUs was initiated by Virtual Pediatric Systems, LLC (Los Angeles, CA; http://www.myvps.org) in mid-March 2020. Information was made available online to all PICUs wishing to participate. A secondary data collection was performed to follow-up on patients discharged from those PICUs reporting coronavirus disease 2019 positive patients.

Measurements and Main Results:

To date, over 180 PICUs have responded detailing 530 PICU admissions requiring over 3,467 days of PICU care with 30 deaths. The preponderance of cases was in the eastern regions. Twenty-four percent of the patients admitted to the PICUs were over 18 years old. Fourteen percent of admissions were under 2 years old. Nearly 60% of children had comorbidities at admission with the average length of stay increasing by age and by severity of comorbidity. Advanced respiratory support was necessary during 67% of the current days of care, with 69% being conventional mechanical ventilation.

Conclusions:

PICUs have been significantly impacted by the pandemic. They have provided care not only for children but also adults. Patients with coronavirus disease 2019 have a high frequency of comorbidities, require longer stays, more ventilatory support than usual PICU admissions. These data suggest several avenues for further exploration.
Hip Abductor Strength and Lower Limb Load on Nonoperating Predict Functional Mobility in Women Patients With Total Hip Arthroplasty
Authors: Murao Masanobu , Nankaku Manabu , Hamada Ryota , Kawano Takumi , Goto Koji , Kuroda Yutaka , Ikeguchi Ryosuke , Matsuda Shuichi
Published: July 2020

Objective

The aim of this study was to identify which aspect of the preoperative lower limb functions is most likely to affect the functional mobility at 6 mos after total hip arthroplasty.

Design

The study subjects included 125 women who underwent total hip arthroplasty. Hip flexion and abduction angles, hip abductor and knee extensor strengths, and lower limb load were measured preoperatively. The Timed Up and Go test was performed 6 mos postoperatively. Then, patients were divided into fast or slow groups as per the comparison with the Timed Up and Go score of healthy women.

Results

Hip abductor strength and lower limb load on the nonoperative side were revealed as significant measurements that affected functional mobility after total hip arthroplasty according to stepwise multiple logistic regression analysis. Moreover, receiver operating characteristic curve analyses showed that the postoperative functional mobility was predicted by the lower limb load of the nonoperative side (cutoff point, 8.97 N/kg; sensitivity, 62.3%; specificity, 82.8%; and area under the curve, 77.5%).

Conclusions

This study revealed that patients with preoperative hip abductor strength of greater than 0.66 Nm/kg and lower limb load of greater than 8.97 N/kg on the nonoperative side could achieve better functional mobility at 6 mos postoperatively than healthy women of the same age group.
The Down Side of Prone Positioning
Authors: Le Minh Quan , Rosales Richard , Shapiro Lauren T. , Huang Laura Y.
Published: July 2020

The coronavirus 2019 pandemic has resulted in a surge of patients with acute respiratory distress syndrome. Prone positioning may be used in such patients to optimize oxygenation. Severe infections may leave survivors with significant functional impairment necessitating rehabilitation. Those who have experienced prolonged prone positioning are at increased risk for complications not typically associated with critical illness. This case report describes the course and clinical findings of a survivor of acute respiratory distress syndrome due to coronavirus 2019 who was prone positioned while in intensive care and subsequently admitted to an inpatient rehabilitation facility. Her related complications, as well as those described in the literature, are reviewed. Critical elements of a comprehensive rehabilitation treatment plan for those who have been prone positioned, including implementation of preventive strategies, as well as early recognition and treatment of related injuries, will be described.
Assessment of Severity in Chronic Thromboembolic Pulmonary Hypertension by Quantitative Parameters of Dual-Energy Computed Tomography
Authors: Tsutsumi Yoshinori , Iwano Shingo , Okumura Naoki , Adachi Shiro , Abe Shinji , Kondo Takahisa , Kato Katsuhiko , Naganawa Shinji
Published: July 2020

Objective

The objective of this study was to assess the correlation between dual-energy computed tomography quantitative parameters and hemodynamics in patients with chronic thromboembolic pulmonary hypertension.

Methods

Dual-energy computed tomography of 52 chronic thromboembolic pulmonary hypertension patients were evaluated retrospectively. The mean lung perfused blood volume (lung PBV) and the mean pulmonary artery (PA) enhancement measured at pulmonary parenchymal phase were compared with the hemodynamics by Spearman rank correlation coefficient (r
s) and receiver operating characteristic analysis.

Results

Lung PBV was correlated with mean pulmonary arterial pressure (r
s = 0.47, P < 0.001). Pulmonary artery enhancement was correlated with cardiac index (r
s = −0.49, P < 0.001) and pulmonary vascular resistance (r
s = 0.48, P < 0.001). The areas under the curves were 0.86 for lung PBV to predict mean pulmonary arterial pressure of >50 mm Hg and 0.86 for PA enhancement to predict pulmonary vascular resistance of >1000 dyne·s/cm5.

Conclusions

Lung PBV and PA enhancement could be indicators of hemodynamics.
Combined Use of an Innervated Radial Forearm Flap and Labia Minora Peripheral Skin Graft for Total Upper Lip Reconstruction
Authors: Kitamura Yutaro , Oki Masanao , Kurita Masakazu , Okazaki Mutsumi
Published: July 2020

The repair of a total lip defect and reconstruction of the vermilion border of the lip is challenging. Here, the authors report the successful functional and esthetic reconstruction of an injured upper lip using a free radial forearm flap and labia minora peripheral skin graft. A 43-year-old woman accidentally fell, resulting in a full-thickness wound in her entire upper lip. One month after the injury, the upper lip was reconstructed with an innervated free radial forearm flap. Six months postoperatively, a Semmes-Weinstein monofilament pressure esthesiometer indicated good recovery of neurosensory function with a value of 2.83. Nine months after the injury, the vermilion border, white roll, and philtrum were reconstructed. The vermilion border was reconstructed using a labia minora peripheral skin graft. The philtrum was reproduced using pigmented skin harvested from the vicinity of the labia minora, and the white roll was reconstructed 3-dimensionally by turning the dermis beneath the skin. Satisfactory results were obtained. The combined use of an innervated free radial forearm flap and labia minora peripheral skin graft may be an option for repairing extensive upper lip defects.
Foreign Body Reaction to Poly-D-L-Lactic Acid Resorbable Plates Used in Craniofacial Surgery
Authors: Cen Nicholas , Davis Matthew J. , Abu-Ghname Amjed , Davies Lesley W. , Patel Kalyani R. , Buchanan Edward P.
Published: July 2020

Resorbable surgical materials are often used in the pediatric population to provide fixation in the growing skeleton. Although foreign body reactions to poly-D-L-lactic acid (PDLLA) plates and screws have been previously reported in other fields, to date PDLLA polymers have been well-tolerated in the setting of craniofacial surgery. The authors report a case of a previously healthy 4-month-old patient with Crouzon syndrome who underwent a frontal-orbital advancement with resorbable PDLLA plates and screws and subsequently experienced extensive foreign body reactions and wound healing complications.
Do Measures of Muscular Fitness Modify the Effect of Intra-abdominal Pressure on Pelvic Floor Support in Postpartum Women?
Authors: Nygaard Ingrid E. , Shaw Janet M. , Wang Jie , Sheng Xiaoming , Yang Meng , Niederauer Stefan , Hitchcock Robert
Published: July 2020

Objective

This study aimed to determine whether measures of muscular fitness modify the effect of intra-abdominal pressure (IAP) during lifting on pelvic floor support.

Methods

Participants, primiparous women 1 year after vaginal delivery, underwent the Pelvic Organ Prolapse Quantification examination, measurement of IAP via a vaginal sensor while lifting a weighted car seat, pelvic floor muscle force assessment using an instrumented speculum, grip strength using a hand dynamometer, and trunk flexor endurance by holding an isometric contraction while maintaining a 60-degree angle to the table. We dichotomized pelvic floor support as worse (greatest descent of the anterior, posterior, or apical vagina during maximal strain at or below the hymen) versus better (all points above the hymen).

Results

Of 825 participants eligible after delivery, 593 (71.9%) completed a 1-year study visit. Mean (SD) age was 29.6 (5.0) years. One year postpartum, 55 (9.3%) demonstrated worse support. There were no differences in IAP during lifting or in other measures of pelvic floor loading between women with better and worse support. In multivariable analyses, neither grip strength nor pelvic floor muscle force modified the effect of IAP on support. In women with trunk flexor endurance duration ≥13 minutes, the odds of worse support increased significantly as IAP increased. No fitness measure modified the effect of other measures of pelvic floor loading on support.

Conclusions

Primiparous women with higher IAP during lifting and greater muscular fitness did not have reduced odds of worse pelvic floor support compared with those with lower IAP at the same muscular fitness.
Rubisco proton production can drive the elevation of CO2within condensates and carboxysomes
Authors: Long Benedict M. , Förster Britta , Pulsford Sacha B. , Price G. Dean , Badger Murray R.
Published: July 2020

Membraneless organelles containing the enzyme Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) are a common feature of organisms utilizing CO2concentrating mechanisms (CCMs) to enhance photosynthetic carbon acquisition. In cyanobacteria and proteobacteria, the Rubisco condensate is encapsulated in a proteinaceous shell, collectively termed a carboxysome, while some algae and hornworts have evolved Rubisco condensates known as pyrenoids. In both cases, CO2fixation is enhanced compared with the free enzyme. Previous mathematical models have attributed the improved function of carboxysomes to the generation of elevated CO2within the organelle via a co-localized carbonic anhydrase (CA), and inwardly diffusing HCO3-which has accumulated in the cytoplasm via dedicated transporters. Here we present a novel concept in which we consider the net of two protons produced in every Rubisco carboxylase reaction. We evaluate this in a reaction-diffusion, compartment model to investigate functional advantages these protons may provide Rubisco condensates and carboxysomes, prior to the evolution of HCO3-accumulation. Our model highlights that diffusional resistance to reaction species within a condensate allows Rubisco-derived protons to drive the conversion of HCO3-to CO2via co-localized CA, enhancing both condensate [CO2] and Rubisco rate. Protonation of Rubisco substrate (RuBP) and product (PGA) plays an important role in modulating internal pH and CO2generation. Application of the model to putative evolutionary ancestors, prior to contemporary cellular HCO3-accumulation, revealed photosynthetic enhancements along a logical sequence of advancements, via Rubisco condensation, to fully-formed carboxysomes. Our model suggests that evolution of Rubisco condensation could be favored under low CO2and low light environments.
Unlocking the Predictive Power of Heterogeneous Data to Build an Operational Dengue Forecasting System
Authors: Manore Carrie , Fairchild Geoffrey , Ziemann Amanda , Parikh Nidhi , Kempfert Katherine , Martinez Kaitlyn , Castro Lauren , Osthus David , Siraj Amir , Conrad Jessica , Generous Nicholas , Del Valle Sara
Published: July 2020

Predicting an infectious disease can help reduce its impact by advising public health interventions and personal preventive measures. While availability of heterogeneous data streams and sensors such as satellite imagery and the Internet have increased the opportunity to indirectly measure, understand, and predict global dynamics, the data may be prohibitively large and/or require intensive data management while also requiring subject matter experts to properly exploit the data sources (e.g., deriving features from fundamentally different data sets). Few efforts have quantitatively assessed the predictive benefit of novel data streams in comparison to more traditional data sources, especially at fine spatio-temporal resolutions. We have combined multiple traditional and non-traditional data streams (satellite imagery, Internet, weather, census, and clinical surveillance data) and assessed their combined ability to predict dengue in Brazil’s 27 states on a weekly and yearly basis over seven years. For each state, we nowcast dengue based on several time series models, which vary in complexity and inclusion of exogenous data. We also predict yearly cumulative risk by municipality and state. The top-performing model and utility of predictive data varies by state, implying that forecasting and nowcasting efforts in the future may be made more robust by and benefit from the use of multiple data streams and models. One size does not fit all, particularly when considering state-level predictions as opposed to the whole country. Our first-of-its-kind high resolution flexible system for predicting dengue incidence with heterogeneous (and still sometimes sparse) data can be extended to multiple applications and regions.
Mapping the evolution of T cell states during response and resistance to adoptive cellular therapy
Authors: Bachireddy Pavan , Azizi Elham , Burdziak Cassandra , Nguyen Vinhkhang N , Ennis Christina , Choo Zi-Ning , Li Shuqiang , Livak Kenneth J. , Neuberg Donna S , Soiffer Robert J , Ritz Jerome , Alyea Edwin P , Pe’er Dana , Wu Catherine J
Published: July 2020

Immune therapies have transformed the cancer therapeutic landscape but fail to benefit most patients. To elucidate the underlying mechanisms by which T cells mediate elimination of leukemia, we generated a high-resolution map of longitudinal T cell dynamics within the same tumor microenvironment (TME) during response or resistance to donor lymphocyte infusion (DLI), a widely used immunotherapy for relapsed leukemia. We analyzed 87,939 bone marrow-derived single T cell transcriptomes, along with chromatin accessibility and single T cell receptor clonality profiles, by developing novel machine learning tools for integrating longitudinal and multimodal data. We found that pre-treatment enrichment and post-treatment rapid, durable expansion of ‘terminal’ (TEX) and ‘precursor’ (TPEX) exhausted subsets, respectively, defined DLI response. A contrasting, heterogeneous pattern of T cell dysfunction marked DLI resistance. Unexpectedly, TPEXcells that expanded in responders did not arise from the infusion product but instead from both pre-existing and novel clonotypes recruited to the TME. Our unbiased dissection of the TME using a Bayesian method, Symphony, defined the T cell circuitry underlying effective human anti-leukemic immune responses that may be broadly relevant to other exhaustion antagonists across cancers. Finally, we provide a general analysis paradigm for exploiting temporal single-cell genomic profiling for deep understanding of therapeutic scenarios beyond oncology.
Intestinal-epithelial LSD1 controls cytoskeletal-mediated cell identity including goblet cell effector responses required for gut inflammatory and infectious diseases
Authors: Parmar Naveen , Burrows Kyle , Lindholm Håvard T. , Zwiggelaar Rosalie T. , Martín-Alonso Mara , Fosslie Madeleine , Vallance Bruce , Dahl John Arne , Zaph Colby , Oudhoff Menno J.
Published: July 2020

Infectious and inflammatory diseases in the intestine remain a serious threat for patients world-wide. Reprogramming of the intestinal epithelium towards a protective effector state is important to manage inflammation and immunity. The role of epigenetic regulatory enzymes within these processes is not yet defined. Here, we use a mouse model that has an intestinal-epithelial specific deletion of the histone demethylaseLsd1(cKO mice), which maintains the epithelium in a fixed reparative state. Challenge of cKO mice with chemical-induced colitis, bacteria-induced colitis, and a helminth infection model all resulted in increased pathogenesis. Mechanistically, we discovered that LSD1 directly controls genes that facilitate cytoskeletal organization, and that this is relevant for epithelial attachment as well as for goblet-cell specific effector responses.This study therefore identifies intestinal-epithelial epigenetic regulation by LSD1 as a critical element in host protection from inflammation and infection.
Weed communities and wheat yield are modified by cropping systems and climate conditions
Authors: Seipel Tim , Ishaq Suzanne L. , Menalled Fabian D.
Published: July 2020

Understanding the impact of biological and environmental stresses on crop performance is essential to secure the long-term sustainability of agricultural production. How cropping systems modify weed communities and wheat yield in response to predicted climate conditions is unknown. We tested the effect of warmer, and warmer and drier conditions on weed biomass, weed community characteristics, and winter wheat yields in three contrasting cropping systems: a no-till chemically managed system, a tilled organic system, and an organic system that used grazing to reduce tillage. Weed communities in the organic systems were more diverse and more variable than the no-till conventional system, though the grazed organic and no-till conventional systems had more similar relative species abundance. Cropping system affected weed biomass and weed species composition recorded in 0.75 m2split-plots, with the most biomass recorded in grazed organic system (38 g ±23.4 SE) compared to the tilled-organic (17 g ±10.3 SE) and no-till chemically managed systems (<1 g ±0.02). Climate conditions had relatively minor impacts on weed communities compared with cropping systems. Wheat yield was highest in the no-till conventional system but declined in response to warmer and drier conditions despite its low weed biomass. Yield was lower in the tilled organic and grazed organic cropping system but declines in warmer and drier conditions were more variable among years. In the Northern Great Plains, predicted climate scenarios have the potential to alter weed communities and reduce wheat yield, and designing resilient cropping systems is essential to mitigate these negative impacts.
Switch-like control of helicase processivity by single-stranded DNA binding protein
Authors: Stekas Barbara , Honda Masayoshi , Spies Maria , Chemla Yann R.
Published: July 2020

Helicases utilize the energy of NTP hydrolysis to translocate along single-stranded nucleic acids (NA) and unwind the duplex. In the cell, helicases function in the context of other NA-associated proteins which regulate helicase function. For example, single-stranded DNA binding proteins are known to enhance helicase activity, although the underlying mechanisms remain largely unknown. F. acidarmanus XPD helicase serves as a model for understanding the molecular mechanisms of Superfamily 2B helicases, and previous work has shown that its activity is enhanced by the cognate single-stranded DNA binding protein RPA2. Here, single-molecule optical trap measurements of the unwinding activity of a single XPD helicase in the presence of RPA2 reveal a mechanism in which XPD interconverts between two states with different processivities and transient RPA2 interactions stabilize the more processive state, activating a latent “processivity switch” in XPD. These findings provide new insights on mechanisms of helicase regulation by accessory proteins.
Influence of Fluorination on Single-Molecule Unfolding and Rupture Pathways of a Mechanostable Protein Adhesion Complex
Authors: Yang Byeongseon , Liu Haipei , Liu Zhaowei , Doenen Regina , Nash Michael A.
Published: July 2020

Fluorination of proteins by cotranslational incorporation of non-canonical amino acids is a valuable tool for enhancing biophysical stability. Despite many prior studies investigating the effects of fluorination on equilibrium stability, its influence on non-equilibrium mechanical stability remains unknown. Here, we used single-molecule force spectroscopy (SMFS) with the atomic force microscope (AFM) to investigate the influence of fluorination on unfolding and unbinding pathways of a mechanically ultrastable bacterial adhesion complex. We assembled modular polyproteins comprising the tandem dyad XModule-Dockerin (XMod-Doc) bound to a globular Cohesin (Coh) domain. By applying tension across the binding interface, and quantifying single-molecule unfolding and rupture events, we mapped the energy landscapes governing the unfolding and unbinding reactions. We then used sense codon suppression to substitute trifluoroleucine (TFL) in place of canonical leucine (LEU) globally in XMod-Doc, or selectively within the Doc subdomain of a mutant XMod-Doc. Although TFL substitution thermally destabilized XMod-Doc, it had little effect on XMod-Doc:Coh binding affinity at equilibrium. When we mechanically dissociated global TFL-substituted XMod-Doc from Coh, we observed the emergence of a new unbinding pathway with a lower energy barrier. Counterintuitively, when fluorination was restricted to Doc, we observed mechano-stabilization of the non-fluorinated neighboring XMod domain. These results suggest that intramolecular deformation networks can be modulated by fluorination, and further highlight significant differences between equilibrium thermostability, where all constructs were destabilized, and non-equilibrium mechanostability, where XMod was strengthened. Future work is poised to investigate the influence of non-natural amino acids on mechanically-accelerated protein unfolding and unbinding reaction pathways.
Denisovan introgression has shaped the immune system of present-day Papuans
Authors: Vespasiani Davide M. , Jacobs Guy S. , Cook Laura E. , Brucato Nicolas , Leavesley Matthew , Kinipi Christopher , Ricaut Francois-Xavier , Cox Murray P. , Romero Irene Gallego
Published: July 2020

Modern humans have substantially admixed with multiple archaic hominins. Papuans, in particular, owe up to 5% of their genome to Denisovans, a sister group to Neanderthals, whose remains have only been identified in Siberia and Tibet. Unfortunately, the biological and evolutionary significance of these introgression events remain poorly understood. Here we investigate the function of archaic alleles of both Denisovan and Neanderthal ancestry characterised within a previously published set of 56 genomes from individuals of Papuan genetic ancestry living in the island of New Guinea. By comparing the distribution of archaic and modern human variants, we are able to assess the consequences of archaic admixture across a multitude of different cell types and functional elements. We detect a consistent signal across Denisovan variants of strong involvement in immune-related processes throughout our analyses. Archaic alleles are often located within cis-regulatory elements and transcribed regions of the genome, suggesting that they are capable of contributing to a wide range of cellular regulatory processes. We identify 3,538 high-confidence Denisovan variants that fall within annotated cis-regulatory elements and have the potential to alter the affinity of multiple transcription factors to their cognate DNA motifs, highlighting a likely mechanism by which introgressed DNA can impact phenotypes in present-day humans. Lastly, we experimentally validate these predictions by testing the regulatory potential of five Denisovan variants segregating at high frequency within Papuan individuals, and find that two are associated with a significant reduction of transcriptional activities in plasmid reporter assays relative to modern human alleles. Together, these data provide support for the hypothesis that, despite their broadly deleterious nature, archaic alleles actively contribute to modern human phenotypic diversity to this day, and might have facilitated early adaptation to non-African environments.
IN-UTERO MOTHER-TO-CHILD SARS-CoV-2 TRANSMISSION: viral detection and fetal immune response
Authors: Fenizia Claudio , Biasin Mara , Cetin Irene , Vergani Patrizia , Mileto Davide , Spinillo Arsenio , Gismondo Maria Rita , Perotti Francesca , Callegari Clelia , Mancon Alessandro , Cammarata Selene , Beretta Ilaria , Nebuloni Manuela , Trabattoni Daria , Clerici Mario , Savasi Valeria
Published: July 2020

Pregnancy is known to increase the risk of severe illnesses in response to viral infections. Therefore, the impact of SARS-CoV-2 infection during gestational ages might be detrimental and the potential vertical transmission should be thoroughly studied.

Herein, we investigated whether SARS-CoV-2 vertical transmission is possible and, in case, whether this results in a fetal involvement. Additionally, we analyzed the role of the antibody and the inflammatory responses in placenta and plasma from SARS-CoV-2-positive pregnant women and fetuses.

31 SARS-CoV-2 pregnant women were enrolled. Real-time PCR was performed to detect the virus on maternal and newborns’ nasopharyngeal swabs, vaginal swabs, maternal and umbilical cord plasma, placenta and umbilical cord biopsies, amniotic fluids and milk. Maternal and umbilical cord plasma, and milk were tested for specific anti-SARS-CoV-2 antibodies. RNA expression quantification of genes involved in the inflammatory response was performed on four selected placentas. On maternal and umbilical cord plasma of the same subjects, secreted cytokines/chemokines were quantified.

SARS-CoV-2 is found in at-term placentae and in the umbilical cord blood, in the vaginal mucosa of pregnant women and in milk. Furthermore, we report the presence of specific anti-SARS-CoV-2 IgM and IgG antibodies in the umbilical cord blood of pregnant women, as well as in milk specimens. Finally, a specific inflammatory response is triggered by SARS-CoV-2 infection in pregnant women at both systemic and placental level, and in umbilical cord blood plasma.

Our data strongly support the hypothesis that in-utero vertical transmission is possible in SARS-CoV-2 positive pregnant women. This is essential for defining proper obstetric management of COVID-19 pregnant women, or putative indications for mode and timing of delivery.
Analysis of electrical circuits supplied by sequence of impulses
Authors: Georgiev Zhivko , Trushev Ivan
Published: July 2020

Purpose

This paper aims to analyze transient and steady state processes in series resistive capacitive-circuits when the supplied voltage is a sequence of periodic rectangular pulses. The purpose is to obtain an analytical formula for the capacitor voltage at any instant of time, both for the transient and the steady-state processes.

Design/methodology/approach

The main approach is to use a combination of differential and recurrence equations.

Findings

An analytical expression (formula) for obtaining the capacitor voltage at any instant of time has been found.

Originality/value

The results obtained are new. They are much more convenient to use than the results obtained by the Fourier series. The exposed approach can also be used in other circuits and other forms of the supplied voltage.
Family planning and budgeting for human rights in India
Authors: Weigelt Thibault , Sharma Erica
Published: July 2020

Purpose

The purpose of this paper is to analyse the budget of the Indian family planning programme from a human rights perspective. Family planning services play an important role in the realisation of the reproductive rights of women. In India, the family planning programme is one of the largest in the world with thousands of patients, mostly women, accessing services every year. Although the Indian legal system guarantees the right to health, Indian women from marginalised sections of society still battle inadequate services and the absence of health care that respects their right to reproductive autonomy and choice. Therefore, the question is: in the presence of a strong legal framework, what are the factors that contribute to this phenomenon?

Design/methodology/approach

The authors have gathered data from the project implementation plans at the state level comparing year-wise expenditure for family planning against overall expenditure for reproductive, maternal and child health expenditure. The data are then compared to the number of women using sterilisation to suggest a relationship between both. Finally, the article relies on desk research to review scholarship on the Indian family planning programme and applicable human rights obligations.

Findings

The paper finds that social-economic rights such as the right to health are applicable to government spending and budgeting. It also finds current spending in the NHM is insufficient to guarantee women’s reproductive rights as the vast majority of resources are spend on sterilisation, thus limiting women’s ability to choose the number and spacing of children.

Research limitations/implications

The data used in this research bears one limitation: the propensity of the government to change the guidelines as to how States should present their budgets in the project implementation plans. The authors have adjusted the data so that it remains comparable. However, the adjustment was not possible for all expenditure data, which is why the current study is limited to the family planning programme alone.

Practical implications

The paper argues that to be human rights compliant, health budgets of the NHM need to be geared towards the specific needs of women in terms of family planning. Finally, the article briefly outlines the role played by human rights and human rights litigation in impacting government budgets.

Originality/value

India’s family planning programme has been examined from a performance and medical standpoint, focussing on medical indicators such as total fertility rate, unmet needs for family planning, amongst others. Academic scholarship has investigated through statistical analysis patterns of contraceptive use and contraceptive mix. What is absent, however, is an assessment of the programme from a right-based perspective by looking at the human rights obligations of India and their normative implications for the Indian family programme.
Comparison of modular and traditional UK housing construction: a bibliometric analysis
Authors: Nazir Falaq , Edwards David John , Shelbourn Mark , Martek Igor , Thwala Wellington Didibhuku Didibhuku , El-Gohary Hatem
Published: July 2020

Purpose

Housing completions in the UK have fallen to 125,000 annually, while government targets have risen to 300,000. This dramatic shortfall raises concerns as to whether current traditional construction approaches remain appropriate. This study aims to compare the traditional approach with modular construction, with a view to assessing whether a shift in construction systems offers the potential to alleviate the UK's domestic housing crisis.

Design/methodology/approach

A comprehensive interpretivist review of the available relevant literature is undertaken on construction methods within the UK; advantages and disadvantages. A bibliometric analysis is conducted to extract trends and findings relevant to the comparison at hand. The database is Web of Science; the analysis software is the VOS viewer.

Findings

The research illustrates that the UK housing market is in a state of crisis. A toxic combination of a rising UK population combined falling rates of housing delivery has resulted in an ever-widening housing supply gap. The construction industry’s capacity to meet this observed dearth in supply is further exacerbated by a number of chronic factors such as: falling participation in the construction sector workforce; lowering skill levels; reducing profitability; time to delivery pressures; and cost blow-outs.

Originality/value

While much information on the various construction methods are available, including comparative material, this study is the first to assemble the various comparative parameters regarding traditional and modular UK residential construction in one place. Thus, this study provides a definitive assessment of the relative advantages and disadvantages of these forms of construction.
Policing partnerships to address youth antisocial behavior: How parental risk‐taking shapes child outcomes
Authors: Mazerolle Lorraine , Cardwell Stephanie M. , Antrobus Emma , Piquero Alex R.
Published: July 2020

Research Summary

Partnerships are an integral part of the working life of police, yet not a lot is known about how such partnerships work to deter and control crime problems. This article explores the impact of a Third Party Policing Partnership involving police and schools coming together to engage with parents to address their child's truancy and antisocial behavior. We report on results from an embedded behavioral economics experiment within the Ability School Engagement Program (ASEP) Trial. ASEP involved 102 young people who were chronically truant from school and randomly allocated to the experimental partnership program (ASEP) or the business‐as‐usual condition. We find that riskier choices made by parents increase the incidence of child self‐reported antisocial behavior (SRASB). Our results show parents in the ASEP condition had greater gains in knowledge of the education laws relative to control. There was a backfire effect for parents in the control group: Their gains in knowledge of the laws led their children to have higher levels of SRASB.

Policy Implications

Policing partnerships are an important part of the future of policing. Police partnerships with schools are a promising approach for engaging parents and young people in a manner that clearly and fairly explains to parents their legal obligations for their child's school attendance. While we do not find that ASEP modified parental risk‐taking behavior, we do find that the ASEP intervention created an insulating effect from the negative outcomes of the business‐as‐usual condition, in which school principals delivered ad hoc bad news to parents about their child's antisocial behavior in a way that was not procedurally just. Policing partnerships are likely to deter antisocial behavior when police work with third party partners who have some type of legislative responsibility. This legislative medium creates opportunities for the police and third parties to better engage and communicate legal responsibilities and the consequences of noncompliance.
Top executives’ early‐life experience and financial disclosure quality: impact from the Great Chinese Famine
Authors: Yao Shouyu , Wang Zhuoqun , Sun Mengyue , Liao Jing , Cheng Feiyang
Published: July 2020

This study investigates the impact of top executives’ Great Chinese Famine experience on firm financial disclosure quality. We find firms led by top executives who experienced the great famine in early life are less likely to conduct fraudulent financial reporting. The famine effect is more pronounced in state‐owned enterprises (SOEs), smaller‐cap, lower‐profitability level firms and firms with weaker external monitoring. Further evidence suggests that top executives with great famine experience show greater tendency to implement secured debt structure, effective internal control and spend less on entertainment and travel costs, which in turn reduce the likelihood of fraudulent financial reporting.
Oral contraceptives and the serotonin 4 receptor: a molecular brain imaging study in healthy women
Authors: Larsen S. V. , Köhler‐Forsberg K. , Dam V. H. , Poulsen A. S. , Svarer C. , Jensen P. S. , Knudsen G. M. , Fisher P. M. , Ozenne B. , Frokjaer V. G.
Published: July 2020

Objective

Sex steroid hormones potently shape brain functions, including those critical to maintain mental health such as serotonin signaling. Use of oral contraceptives (OCs) profoundly changes endogenous sex steroid hormone levels and dynamics. Recent register‐based studies show that starting an OC is associated with increased risk of developing depression. Here, we investigate whether use of OCs in healthy women is associated with a marker of the serotonin system in terms of serotonin 4 receptor (5‐HT4R) brain imaging.

Methods

[11C]SB207145‐PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5‐HT4R binding in a latent variable model based on 5‐HT4R binding across cortical and subcortical regions.

Results

We demonstrate that OC users have 9–12% lower global brain 5‐HT4R binding potential compared to non‐users. Univariate region‐based analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (−12.8% (95% CI [−21.0; −3.9], Pcorrected = 0.03).

Conclusion

We show that women who use OCs have markedly lower brain 5‐HT4R binding relative to non‐users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5‐HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.