bluuebunny/crossref_metadata_2025 huggingface dataset:
Juvenile social isolation immediately affects the synaptic activity and firing property of fast-spiking parvalbumin-expressing interneuron subtype in mouse medial prefrontal cortex
Authors: Okamura Kazuya , Yoshino Hiroki , Ogawa Yoichi , Yamamuro Kazuhiko , Kimoto Sohei , Yamaguchi Yasunari , Nishihata Yosuke , Ikehara Minobu , Makinodan Manabu , Saito Yasuhiko , Kishimoto Toshifumi
Published: August 2022

A lack of juvenile social experience causes various behavioral impairments and brain dysfunction, especially in the medial prefrontal cortex (mPFC). Our previous studies revealed that juvenile social isolation for 2 weeks immediately after weaning affects the synaptic inputs and intrinsic excitability of fast-spiking parvalbumin-expressing (FSPV) interneurons as well as a specific type of layer 5 (L5) pyramidal cells, which we termed prominent h-current (PH) cells, in the mPFC. However, since these changes were observed at the adult age of postnatal day 65 (P65), the primary cause of these changes to neurons immediately after juvenile social isolation (postnatal day 35) remains unknown. Here, we investigated the immediate effects of juvenile social isolation on the excitability and synaptic inputs of PH pyramidal cells and FSPV interneurons at P35 using whole-cell patch-clamp recording. We observed that excitatory inputs to FSPV interneurons increased immediately after juvenile social isolation. We also found that juvenile social isolation increases the firing reactivity of a subtype of FSPV interneurons, whereas only a fractional effect was detected in PH pyramidal cells. These findings suggest that juvenile social isolation primarily disturbs the developmental rebuilding of circuits involving FSPV interneurons and eventually affects the circuits involving PH pyramidal cells in adulthood.
Venous Thromboembolism Following Discharge from Hospital in Patients Admitted for Inflammatory Bowel Disease
Authors: Harvey Philip R , Coupland Benjamin , Mytton Jemma , De Silva Shanika , Trudgill Nigel J
Published: August 2022

Background and Aims

Patients admitted to hospital with inflammatory bowel disease[IBD] are at increased risk of venous thromboembolism[VTE]. This study aims to identify IBD patients at increased VTE risk on hospital discharge and to develop a risk scoring system to recognise them.

Methods

Hospital episode statistics data were used to identify all patients admitted with IBD as an emergency or electively for surgery. All patients with VTE within 90 days of hospital discharge were identified. A multilevel logistic regression model was used to identify patient- and admission-level factors associated with VTE. A scoring system to identify patients at higher risk for VTE was constructed.

Results

A total of 201 779 admissions in 101 966 patients were included. The rate of VTE within 90 days was 17.2 per 1000 patient-years at risk and was highest in patients admitted as an emergency who underwent surgery[36.9]. VTE was associated with: female sex (odds ratio 0.65 [95% confidence interval 0.53-0.80], p <0.001); increasing age [49–60 years] (4.67 [3.36-6.49], p <0.001); increasing length of hospital stay [>10 days] (3.80 [2.80-5.15], p <0.001); more than two hospital admissions in previous 3 months (2.23 [1.60-3.10], p <0.001); ulcerative colitis (1.48 [1.21-1.82], p <0.001); and emergency admission including surgery (1.59 [1.12-2.27], p = 0.010); or emergency admission not including surgery (1.59 [1.08-2.35], p = 0.019) compared with elective surgery. A score >12 in the VTE scoring system gave a positive predictive value [PPV] of VTE of 1%. The area under the curve [AUC] was 0.714 [95% CI 0.70-0.73].

Conclusion

IBD patients admitted to hospital with a prolonged length of stay, increasing age, male sex, or as an emergency were at increased risk of VTE following discharge. Higher-risk patients were identifiable by a VTE risk scoring system.
Time trends in incidence, treatment, and outcome in acute myocardial infarction in Norway 2013–19
Authors: Jortveit Jarle , Pripp Are Hugo , Langørgen Jørund , Halvorsen Sigrun
Published: August 2022

Aims

Acute myocardial infarction (AMI) is a common cause of morbidity and mortality. The aim of the present study was to assess time trends in the incidence, treatment, and outcome of AMI in a nationwide registry–based cohort of patients.

Methods and results

All patients with a first AMI registered in the Norwegian Myocardial Infarction Registry between 2013 and 2019 were included in this cohort study. The number of patients admitted to Norwegian hospitals with a first AMI decreased from 8933 in 2013 to 8383 in 2019. The proportion of patients with ST-elevation myocardial infarction (STEMI) was stable at 30% throughout the period, and the percentage of STEMI undergoing coronary angiography was stable at 87%. The proportion of patients with non-STEMI undergoing coronary angiography increased by 2.4% per year (95% confidence interval 1.6–3.3) from 58% in 2013 to 68% in 2019. More patients were discharged with secondary preventive medication at the end of study period. Age-adjusted 1-year mortality was reduced from 16.4% in 2013 to 15.1% in 2018. The changes over time were primarily seen in the oldest patient groups.

Conclusion

In the period 2013–19 in Norway, we found a reduction in hospitalizations due to a first AMI. Both the percentage of patients undergoing coronary angiography as well as the percentage discharged with recommended secondary preventive therapy increased during the period, and the age-adjusted 1-year mortality after AMI decreased. A national AMI register provides important information about trends in incidence, treatment, and outcome, and may improve adherence to guideline recommendations.
Non-pharmacological factors for hypertension management: a systematic review of international guidelines
Authors: Maniero Carmela , Lopuszko Aleksandra , Papalois Kyriaki-Barbara , Gupta Ajay , Kapil Vikas , Khanji Mohammed Y
Published: August 2022

Lifestyle modifications are one of the cornerstones of hypertension prevention and treatment. We aimed to systematically review hypertension guidelines on their recommendations on non-pharmacological factors including lifestyle interventions, to highlight strength of evidence, similarities, and differences. This systematic review was registered with the international Prospective Register of Systematic Reviews (CRD42021288815). Publications in MEDLINE and EMBASE databases over 10 years since January 2010 to June 2020 were identified. We also included the search from websites of organizations responsible for guidelines development. Two reviewers screened the titles and abstracts to identify relevant guidelines. Two reviewers independently assessed rigour of guideline development using the AGREE II instrument, and one reviewer extracted recommendations. Of the identified guidelines, 10 showed good rigour of development (AGREE II ≥ 60%) and were included in the systematic review. The guidelines were consistent in most recommendations (reduced salt intake, weight, dietary patterns, increased physical activity and smoking cessation, and limiting alcohol intake). Some areas of disagreement were identified, regarding recommendations on novel psychological and environmental factors such as stress or air pollution, alcohol intake thresholds, meat, coffee and tea consumption and refined sugars. Current guidelines agree on the importance of lifestyle in the treatment and prevention of hypertension. Consensus on smoking cessation, limited salt intake, increased physical activity support their integration in management of hypertensive patients and in public health measurements in general population as preventative measurements. Further research into the role of environmental and psychological factors may help clarify future recommendations.
A Practical Guide to Design and Assess a Phylogenomic Study
Authors: Lozano-Fernandez Jesus
Published: August 2022

Over the last decade, molecular systematics has undergone a change of paradigm as high-throughput sequencing now makes it possible to reconstruct evolutionary relationships using genome-scale datasets. The advent of “big data” molecular phylogenetics provided a battery of new tools for biologists but simultaneously brought new methodological challenges. The increase in analytical complexity comes at the price of highly specific training in computational biology and molecular phylogenetics, resulting very often in a polarized accumulation of knowledge (technical on one side and biological on the other). Interpreting the robustness of genome-scale phylogenetic studies is not straightforward, particularly as new methodological developments have consistently shown that the general belief of “more genes, more robustness” often does not apply, and because there is a range of systematic errors that plague phylogenomic investigations. This is particularly problematic because phylogenomic studies are highly heterogeneous in their methodology, and best practices are often not clearly defined. The main aim of this article is to present what I consider as the ten most important points to take into consideration when planning a well-thought-out phylogenomic study and while evaluating the quality of published papers. The goal is to provide a practical step-by-step guide that can be easily followed by nonexperts and phylogenomic novices in order to assess the technical robustness of phylogenomic studies or improve the experimental design of a project.
The geometry of active shortening in the northwest Himalayas and the implications for seismic hazard
Authors: O’Kane Aisling , Copley Alex , Mitra Supriyo , Wimpenny Sam
Published: August 2022

Large thrust faults accommodate the convergence between India and Tibet along the southern margin of the Himalaya and have a history of producing great earthquakes that cause widespread damage. Along most parts of the Himalaya, there is geomorphological evidence that these thrusts can rupture to the surface in Mw >8 earthquakes. However, in the Himalayan state of Jammu & Kashmir (NW India), the thrust faults are blind and large-scale folding is the only expression of active deformation at the surface, making it difficult to assess the seismic hazard in this region. In this paper, we use field, satellite, and seismological observations to determine the fault geometry in Jammu & Kashmir. We then estimate the ground motions from potential earthquakes in the region using models of the seismic wavefield that would be generated if the thrust fault beneath Jammu & Kashmir were to rupture. We find that earthquakes that rupture the buried, shallow part of the locked Main Himalayan Thrust could generate peak ground velocities that are >3 times larger than earthquakes of the same magnitude on its deeper portions. We also model the ground motions that would result from the thrust fault geometries representative of different parts of the Himalayan arc. These simulations show that even seemingly minor variations in the shallow fault geometry can lead to large differences in the expected ground motions, highlighting the importance of accurately determining the shallow geometry of thrust faults along the margins of mountain ranges for estimating seismic hazard.
What’s Up, Latin America? Between Competition, Data and Consumer Protection
Authors: Canales Maria Paz , de Souza Michel Roberto
Published: August 2022

There is no doubt as to the growing importance of personal data to companies. Along with this fact, there is an exponential growth of data concentration on the hands of the biggest global technology companies. Regulators around the world are taking action in digital markets, either through legislation or judicial enforcement, to address the implications of data concentration. This article analyzes a true paradigm shift in the collaboration between antitrust, data protection and consumer authorities in handling the case of changes to WhatsApp’s privacy policy in Argentina, Brazil and Chile. We analyze how the institutional arrangements favored (or not) a more connected and integrated role of different authorities in the investigation of abuses of dominant position, which resulted in a stronger message for actors in the digital market. Institutional factors, such as operational and enforcement capabilities, are also analyzed with regard to the ability and effectiveness of the authorities in these countries to intervene. This article attempts to bring critical considerations in the evaluation of Latin American cases compared with international evolution to drive some useful lessons for future enforcement.
Better healthcare can reduce the risk of COVID-19 in-hospital post-partum maternal death: evidence from Brazil
Authors: Leung Char , Su Li , Simões e Silva Ana Cristina
Published: August 2022

Objective

COVID-19 in post-partum women is commonly overlooked. The present study assessed whether puerperium is an independent risk factor of COVID-19 related in-hospital maternal death and whether fatality is preventable in the Brazilian context.

Methods

We retrospectively studied the clinical data of post-partum/pregnant patients hospitalized with COVID-19 gathered from a national database that registered severe acute respiratory syndromes (SIVEP-Gripe) in Brazil. Logistic regressions were used to examine the associations of in-hospital mortality with obstetric status and with the type of public healthcare provider, adjusting for socio-demographic, epidemiologic, clinical and healthcare-related measures.

Results

As of 30 November 2021, 1943 (21%) post-partum and 7446 (79%) pregnant patients of age between 15 and 45 years with COVID-19 that had reached the clinical endpoint (death or discharge) were eligible for inclusion. Case-fatality rates for the two groups were 19.8% and 9.2%, respectively. After the adjustment for covariates, post-partum patients had almost twice the odds of in-hospital mortality compared with pregnant patients. Patients admitted to private (not-for-profit) hospitals, those that had an obstetric centre or those located in metropolitan areas were less likely to succumb to SARS-CoV-2 infection. Those admitted to the Emergency Care Unit had similar mortality risk to those admitted to other public healthcare providers.

Conclusion

We demonstrated that puerperium was associated with an increased odds of COVID-19-related in-hospital mortality. Only part of the risk can be reduced by quality healthcare such as non-profit private hospitals, those that have an obstetric centre or those located in urban areas.
U.S. Public Support for the U.S.-NATO Alliance
Authors: Lee Kyung Suk , Goidel Kirby
Published: August 2022

While previous research has thoroughly investigated the structure of Americans’ foreign policy beliefs, existing literature tells us far less about the determinants of public support for U.S. military alliances. In the following paper, we examine whether former President Donald Trump’s framing altered public support for the U.S.-North Atlantic Treaty Organization (NATO) military alliance. First, using survey data from the Chicago Council on Global Affairs, we show that support for NATO became polarized after 2016. Second, employing a survey experiment, we test two causal mechanisms that might explain these shifts: (1) a framing model positing that reframing the alliance to emphasize financial costs decreased public support and (2) a cue-taking model positing that opinion on NATO realigned to conform to (or reject) former President Trump’s stated positions. Our experimental results reveal that reframing the alliance decreased support for NATO while the presence of a partisan cue had little or no effect.
Design and analysis of feeder mechanism for buckling prevention in robotic catheterization
Authors: Baek Hyunwoo , Cheon Byungsik , You Jae Min , Kwon Dong-Soo
Published: August 2022

In this study, a novel two-degree-of-freedom active-feeder mechanism with a disposable roller module for buckling prevention of the catheter tube was developed and analyzed. The buckling phenomenon occurs when the flexible part cannot withstand a compressive force. Buckling can be prevented using additional parts that support the long flexible part along the tube; however, these passive-type buckling-prevention mechanisms cannot improve transmissibility in a rotational motion. By contrast, the active-type mechanism can transmit both translational and rotational motion but has a bulky structure due to additional motors, which makes placing the mechanism near the patient difficult. Therefore, to solve the afore-mentioned issues, a compact and clinically practicable design is proposed. The proposed feeder mechanism was developed using two driving-shaft modules that enable simultaneous translational and rotational feeding with the minimum number of motors. Furthermore, to minimize the deformation of the tube and obtain sufficient grip force to replicate surgeons’ operation, the analysis was conducted based on contact mechanics. The maximum insertion force and rotating torque were estimated and verified using the measured static friction coefficient. In addition, we formulated an accurate insertion length model based on the experimental results. Using the proposed feeder mechanism and accurate insertion model, the buckling prevention and elimination performance were verified through the experiment on the robot system.
Computational homogenization of additively manufactured lightweight structures with multiscale topology optimization
Authors: Kim Jae-Eun , Cho Nak-Kyun , Park Keun
Published: August 2022

Topology optimization (TO) is an optimal design method to obtain an efficient structure with minimal usage of material by satisfying two conflicting objectives of weight reduction and structural safety. Owing to the recent advances in additive manufacturing technology, TO has been developed in connection with the use of microscale lattices, of which complicated geometries require considerable computational loads to verify their structural performance. This study aims to develop an efficient computational method to analyze a complex TO model. Computational homogenization was then developed for efficient computation of the TO model that contains a number of microscale lattices. The proposed homogenization scheme was then applied to perform three-dimensional (3D) finite element analysis (FEA) on various TO models with three scales (i.e., macroscale, microscale, and multiscale TOs). The homogenized FEAs were conducted to verify the static and dynamic deformation behaviors of three optimized meta-sandwich beams, and their results and computational efficiency were compared with those from full solid FEAs. Experimental verification revealed that the proposed homogenized FEA provided more reliable results and better computational efficiency for the microscale and multiscale TO models, whereas the conventional solid FEA was advantageous for the macroscale TO model. To apply the proposed simulation strategy to a more complex 3D geometry, three TO models were calculated for a 3D block under a compression load. The simulation strategy combining the full solid and homogenized FEAs was then applied to analyze the static and dynamic deformation behaviors of various TO models, which provided reliable predictions of the experimentally observed behaviors within an acceptable computational time.
Market Maker Inventory, Bid–Ask Spreads, and the Computation of Option Implied Risk Measures
Authors: Eraker Bjørn , Osterrieder Daniela
Published: August 2022

We present empirical evidence showing that option-implied risk measures (OIRMs) are substantially impacted by bid–ask spreads in underlying options. Asking prices are more sensitive to shocks than bids, leading to highly skewed distributions of spreads. We derive and estimate a model of market making that empirically matches these asymmetric responses as well as the time-series properties of bid–ask spreads. Using these estimates to obtain bias-corrected option quotes, we compute several popular OIRMs. We find that fear and risk premia associated with market events that affect the center of the return distribution or unpredictable return jumps are on average overstated when relying on option mid-quotes, whereas risk associated with return-tail events is larger once the bias has been corrected.
Photometric variability in star-forming galaxies as evidence for low-mass AGN and a precursor to quenching
Authors: Cleland Cressida , McGee Sean L
Published: August 2022

We measure the optical variability in ∼16 500 low-redshift (z ∼ 0.1) galaxies to map the relations between active galactic nucleus (AGN) activity and galaxy stellar mass, specific star formation rate, half-light radius, and bulge-to-total ratio. To do this, we use a reduced χ2 variability measure on >10 epoch light curves from the Zwicky Transient Facility and combine with spectroscopic data and derive galaxy parameters from the Sloan Digital Sky Survey. We find that below the stellar mass of 1011 M⊙, galaxies classed as star-forming via the Baldwin–Phillips–Terlevich diagram have higher mean variabilities than AGN or composite galaxies. Revealingly, the highest mean variabilities occur in star-forming galaxies in a narrow range of specific star formation rate: −11 < log(sSFR/yr−1) < −10. In very actively star-forming galaxies [log(sSFR/yr−1) > −10], the reduced variability implies a lack of instantaneous correlation with star formation rate. Our results may indicate that a high level of variability, and thus black hole growth, acts as a precursor for reduced star formation, bulge growth, and revealed AGN-like emission lines. These results add to the mounting evidence that optical variability can act as a viable tracer for low-mass AGNs and that such AGNs can strongly affect their host galaxy.
On the response of a star cluster to a tidal perturbation
Authors: Martinez-Medina Luis A , Gieles Mark , Gnedin Oleg Y , Li Hui
Published: August 2022

We study the response of star clusters to individual tidal perturbations using controlled N-body simulations. We consider perturbations by a moving point mass and by a disc, and vary the duration of the perturbation as well as the cluster density profile. For fast perturbations (i.e. ‘shocks’), the cluster gains energy in agreement with theoretical predictions in the impulsive limit. For slow disc perturbations, the energy gain is lower, and this has previously been attributed to adiabatic damping. However, the energy gain due to slow perturbations by a point-mass is similar to, or larger than that due to fast shocks, which is not expected because adiabatic damping should be almost independent of the nature of the tides. We show that the geometric distortion of the cluster during slow perturbations is of comparable importance for the energy gain as adiabatic damping, and that the combined effect can qualitatively explain the results. The half-mass radius of the bound stars after a shock increases up to ∼7 per cent for low-concentration clusters, and decreases ∼3 per cent for the most concentrated ones. The fractional mass loss is a non-linear function of the energy gain, and depends on the nature of the tides and most strongly on the cluster density profile, making semi-analytic model predictions for cluster lifetimes extremely sensitive to the adopted density profile.
Effectiveness of school-based nutrition intervention components on fruit and vegetable intake and nutrition knowledge in children aged 4–12 years old: an umbrella review
Authors: Verdonschot Angeliek , Follong Berit M , Collins Clare E , de Vet Emely , Haveman-Nies Annemien , Bucher Tamara
Published: August 2022

Context

School-based nutrition interventions can support healthy eating in children.

Objective

To identify components of school-based nutrition interventions and synthesize the impact on consumption of fruits and vegetables (FV) and nutrition knowledge (NK) in children aged 4–12 y.

Data sources

Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and PICOS inclusion criteria, relevant systematic reviews and/or meta-analyses, written in English, published between 2010 and August 2020, across 6 databases were identified.

Data extraction

Two reviewers independently performed data extraction and assessed the study quality.

Data analysis

The JBI Critical Appraisal Instrument for Systematic Reviews and Research Syntheses was used to assess review quality, and the Grading of Recommendations Assessment, Development, and Evaluation approach was used to rate strength of evidence.

Results

From 8 included reviews, 7 intervention components were identified: FV provision, gaming/computer-delivered, curriculum, experiential learning, reward/incentives, nudging, and caregiver involvement. FV provision had the greatest effect on F intake, gaming/computer-delivered on V intake, and curriculum on NK.

Conclusion

FV provision and gaming/computer-delivered components showed, overall, some positive effect on FV intake, as did the curriculum component on NK. More evidence evaluating single-component effectiveness that considers the setting and context of nutrition interventions is required to strengthen the evidence base.

Systematic Review Registration

PROSPERO, registration no.: CRD42020152394.
The Phase II Study of Panitumumab in Chemotherapy-Naïve Frail or Elderly Patients with RAS Wild-type Colorectal Cancer: OGSG 1602 Final Results
Authors: Terazawa Tetsuji , Kato Takeshi , Goto Masahiro , Ohta Katsuya , Satake Hironaga , Noura Shingo , Kagawa Yoshinori , Kawakami Hisato , Hasegawa Hiroko , Yanagihara Kazuhiro , Shingai Tatsushi , Nakata Ken , Kotaka Masahito , Hiraki Masayuki , Konishi Ken , Nakae Shiro , Sakai Daisuke , Kurokawa Yukinori , Shimokawa Toshio , Tsujinaka Toshimasa , Satoh Taroh
Published: August 2022

Background

We previously reported the response rate of a phase II OGSG1602 study on panitumumab in chemotherapy-naive frail or elderly patients with RAS wild-type unresectable colorectal cancer (CRC) [Terazawa T, Kato T, Goto M, et al. Oncologist. 2021;26(1):17]. Herein, we report a survival analysis.

Methods

Patients aged ≥65 years and considered unsuitable for intensive chemotherapy or aged ≥76 years were enrolled. Primary tumors located from the cecum to the transverse colon were considered right-sided tumors (RSTs); those located from the splenic flexure to the rectum were considered left-sided tumors (LSTs).

Results

Among the 36 enrolled patients, 34 were included in the efficacy analysis, with 26 and 8 having LSTs and RSTs, respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.0 [95% CI, 5.4-10.0] and 17.5 months (95% CI, 13.8-24.3), respectively. Although no significant differences existed in PFS between patients with LST and RST {6.6 (95% CI, 5.4-11.5) vs. 4.9 months [95% CI, 1.9-not available (NA), P = .120]}, there were significant differences in OS [19.3 (95% CI, 14.2-NA) vs.12.3 months (95% CI, 9.9-NA), P = .043].

Conclusion

Panitumumab showed favorable OS in frail or elderly patients with RAS wild-type CRC and no prior exposure to chemotherapy. Panitumumab may be optimal for patients with LSTs (UMIN Clinical Trials Registry Number UMIN000024528).
In Reply to the Comment on “The Relationship Between Frailty and Emotional Health in Older Patients With Advanced Cancer”
Authors: Gilmore Nikesha , Culakova Eva , Mohile Supriya
Published: August 2022

This letter to the editor responds to comments on an article that reported on the prevalence of frailty, anxiety, depression, and distress and the relationships between frailty and emotional health in older patients with advanced cancer.
Factors Associated With Physical Activity Levels in Patients With Breast Cancer
Authors: Marell Paulina S , Vierkant Robert A , Olson Janet E , Herrmann Joerg , Larson Nicole , LeBrasseur Nathan K , D’Andre Stacy D , Cheville Andrea L , Barksdale Toure , Loprinzi Charles L , Couch Fergus , Ruddy Kathryn J
Published: August 2022

Physical activity (PA) is associated with improvement in breast cancer treatment-related symptoms and survival, yet most breast cancer survivors do not meet national PA guidelines. This study aimed to identify characteristics of participants that were associated with an increased likelihood of meeting PA guidelines. Adults with breast cancer seen at Mayo Clinic (Rochester, MN) were surveyed regarding their PA participation, and those who self-reported at least 150 minutes of moderate and/or strenuous aerobic PA weekly on average were considered to be “meeting guidelines”. Three thousand participants returned PA data. Younger age, completion of the survey 7-12 years after diagnosis, absence of recurrence, no bilateral mastectomy, absence of metastatic disease, and lower BMI at the time of survey completion were associated with PA participation (P < .05 in univariate and multivariate analyses). Findings were similar when a threshold of 90 minutes was applied. These results may inform the development of targeted PA-facilitating interventions.
Antibiotic Exposure Does Not Impact Immune Checkpoint Blockade Response in MSI-H/dMMR Metastatic Colorectal Cancer: A Single-Center Experience
Authors: Serpas Higbie Victoria , Rogers Jane , Hwang Hyunsoo , Qiao Wei , Xiao Lianchun , Dasari Arvind , Mola-Rudd Kerri , Morris Van K , Wolff Robert A , Raghav Kanwal , Huey Ryan , Parseghian Christine , Willis Jason , Kopetz Scott , Overman Michael J , Johnson Benny
Published: August 2022

Background

Immune checkpoint blockade (ICB) has improved outcomes for patients with microsatellite instability high (MSI-H)/deficient mismatch repair (dMMR) tumors. However, not all MSI-H/dMMR patients will exhibit the same ICB efficacy. Previous studies suggest that concomitant antibiotic use while receiving ICB may result in poorer outcomes. We aimed to evaluate this association in patients with MSI-H/dMMR metastatic colorectal cancer (mCRC).

Materials and Methods

A single-site, retrospective review of 57 patients with MSI-H/dMMR mCRC that received ICB was completed. Data collected included patient demographics, ICB information, and antibiotic use. Antibiotic exposure was considered from 90 days prior to ICB through 6 weeks after initiation. Primary endpoint was overall response rate (ORR).

Results

The majority of patients received pembrolizumab (27 [47%]) or nivolumab (17 [30%]) monotherapy as their ICB agent. Of the 57 patients, 19 (33.3%) had antibiotic exposure from 90 days prior to ICB initiation through 6 weeks after initiation with most (13 [68%]) having antibiotic use in the 30 days preceding ICB initiation. Similar ORRs were seen in both groups (P-value > .99). No difference was observed in OS (P-value .29) or PFS (P-value .36) between groups.

Conclusion

Our data show no association of lower response rates or survival in those MSI-H/dMMR patients with mCRC who receive antibiotics around the initiation of ICB. This information needs to be confirmed in a larger prospective cohort.
Metal Saturated Cumulates from Siberia — Lunar Basalt Analogues?
Authors: Ballhaus Chris , Leitzke Felipe P , Fonseca Raúl O C , Nagel Thorsten , Kuzmin Dmitri , El Goresy Ahmed
Published: August 2022

It is not well known which chemical differentiation pathways basaltic melts will take when they are iron metal saturated. Thermodynamically, the pathway seems predictable. So long as Fe metal is a stable liquidus phase and relative oxygen fugacity (fO2) is not subject to major fluctuations, the activity of FeO (aFeOmelt) is buffered by the iron–wüstite (IW) equilibrium 2Femetal + O2 → 2FeOmelt. Metallic Fe also stabilizes olivine through the equilibrium 2Femetal + O2 + SiO2 melt → Fe2SiO4 olivine. That equilibrium tends to suppress the enrichment in bulk SiO2 when Fe saturated basaltic melts differentiate. We document the differentiation history of tholeiitic cumulates from the Siberian craton that carry up to 30 modal % metallic Fe. Our study is complemented by differentiation experiments at two redox states, one set in Fe metal capsules at 1.6 log units below IW (IW-1.6) and a second set in graphite capsules at IW + 1.5. Iron saturated differentiation pathways do not show enrichments in FeO nor in bulk SiO2 because olivine remains stable along the entire liquid line of descent. By contrast, melts equilibrated at IW + 1.5, that is, outside metallic Fe saturation, crystallize pigeonite as first silicate and follow a normal (terrestrial) differentiation pathway involving marked SiO2 enrichment. The Fe-saturated path duplicates in detail the liquid line of descent we derive for the cumulates. Iron-saturated experiments have limited applicability to the Earth because there are so few terrestrial basalts saturated with metallic Fe; however, they might apply to the Moon. Many lunar basalts appear to have been saturated with an Fe-Ni phase during their emplacement on the lunar surface, and potentially during generation within the lunar mantle.
Model-assisted ideotyping reveals trait syndromes to adapt viticulture to a drier climate
Authors: Dayer Silvina , Lamarque Laurent J , Burlett Régis , Bortolami Giovanni , Delzon Sylvain , Herrera José C , Cochard Hervé , Gambetta Gregory A
Published: August 2022

Climate change is challenging the resilience of grapevine (Vitis), one of the most important crops worldwide. Adapting viticulture to a hotter and drier future will require a multifaceted approach including the breeding of more drought-tolerant genotypes. In this study, we focused on plant hydraulics as a multi-trait system that allows the plant to maintain hydraulic integrity and gas exchange rates longer under drought. We quantified a broad range of drought-related traits within and across Vitis species, created in silico libraries of trait combinations, and then identified drought tolerant trait syndromes. By modeling the maintenance of hydraulic integrity of current cultivars and the drought tolerant trait syndromes, we identified elite ideotypes that increased the amount of time they could experience drought without leaf hydraulic failure. Generally, elites exhibited a trait syndrome with lower stomatal conductance, earlier stomatal closure, and a larger hydraulic safety margin. We demonstrated that, when compared with current cultivars, elite ideotypes have the potential to decrease the risk of hydraulic failure across wine regions under future climate scenarios. This study reveals the syndrome of traits that can be leveraged to protect grapevine from experiencing hydraulic failure under drought and increase drought tolerance.
Rhamnosyltransferases involved in the biosynthesis of flavone rutinosides in Chrysanthemum species
Authors: Wu Qing-Wen , Wei Min , Feng Ling-Fang , Ding Li , Wei Wu-Ke , Yang Jin-Fen , Lin Xiao-Jing , Liang Hui-Lin , Zhan Ruo-Ting , Ma Dong-Ming
Published: August 2022

Linarin (acacetin-7-O-rutinoside), isorhoifolin (apigenin-7-O-rutinoside), and diosmin (diosmetin-7-O-rutinoside) are chemically and structurally similar flavone rutinoside (FR) compounds found in Chrysanthemum L. (Anthemideae, Asteraceae) plants. However, their biosynthetic pathways remain largely unknown. In this study, we cloned and compared FRs and genes encoding rhamnosyltransferases (RhaTs) among eight accessions of Chrysanthemum polyploids. We also biochemically characterized RhaTs of Chrysanthemum plants and Citrus (Citrus sinensis and Citrus maxima). RhaTs from these two genera are substrate-promiscuous enzymes catalyzing the rhamnosylation of flavones, flavanones, and flavonols. Substrate specificity analysis revealed that Chrysanthemum 1,6RhaTs preferred flavone glucosides (e.g. acacetin-7-O-glucoside), whereas Cs1,6RhaT preferred flavanone glucosides. The nonsynonymous substitutions of RhaTs found in some cytotypes of diploids resulted in the loss of catalytic function. Phylogenetic analysis and specialized pathways responsible for the biosynthesis of major flavonoids in Chrysanthemum and Citrus revealed that rhamnosylation activity might share a common evolutionary origin. Overexpression of RhaT in hairy roots resulted in 13-, 2-, and 5-fold increases in linarin, isorhoifolin, and diosmin contents, respectively, indicating that RhaT is mainly involved in the biosynthesis of linarin. Our findings not only suggest that the substrate promiscuity of RhaTs contributes to the diversity of FRs in Chrysanthemum species but also shed light on the evolution of flavone and flavanone rutinosides in distant taxa.
Expanding Footprints: The Impact of Passenger Transportation on Corporate Locations
Authors: Lin Yatang , Qin Yu , Sulaeman Johan , Yan Jubo , Zhang Jialiang
Published: August 2022

This article investigates how transportation networks shape firms’ geographic footprint by reducing monitoring costs of distant investments. Exploiting the staggered expansions of China’s passenger high-speed rail (HSR) network, we document that the amount of intercity investment between a pair of cities increases by 45% with the introduction of an HSR line connecting the cities. We enhance the causal inference by applying high-dimensional fixed effects, and focusing on city pairs that are “accidentally” connected in the network. The HSR effect is the strongest in industries that require on-site monitoring, as well as for controlling stakes in large distant investments.
Decomposing Long Bond Returns: A Decentralized Theory
Authors: Carr Peter , Wu Liuren
Published: August 2022

Classic bond pricing centralizes bond valuation across all maturities by specifying the dynamics of the short-term interest rate. This article develops a decentralized theory that prices each bond based purely on the near-term behavior of the bond’s own yield. The theory levers the domain expertise of an investor on a particular bond and allows the investor to make pricing and investment analysis on the bond without the shackles of an ambitious centralizing mandate. The theory decomposes the short-term return on a bond with respect to the variation of its own yield. Imposing no dynamic arbitrage on the return decomposition leads to a simple pricing equation relating the bond yield to the market pricing and conditional mean and variance forecasts of the yield’s near-term change. The article illustrates the theory’s applications in decentralized investment of a single bond and in the construction and investment of decentralized butterfly bond portfolios.
Protective effect of cilostazol and verapamil against thioacetamide-induced hepatotoxicity in rats may involve Nrf2/GSK-3β/NF-κB signaling pathway
Authors: Elsisi Alaa E , Elmarhoumy Esraa H , Osman Enass Y
Published: August 2022

Background

Verapamil (VER) and cilostazol (Cilo) are mostly used as cardiovascular drugs; they have beneficial effects on different organs toxicities.

Aim

we investigated whether the Nuclear factor erythroid 2-related factor 2 (Nrf2), Glycogen synthase kinase-3β (GSK-3β), and Nuclear factor-kappa B (NF-κB) pathway involved in the protective role of these drugs against Thioacetamide (TAA) induced hepatotoxicity.

Method

male rats were randomized divided into five groups, each group (n = 10): control, TAA, VER+TAA, Cilo+TAA, and VER+Cilo+TAA groups. Hepatotoxicity induced in rats by TAA injection once on the 7th day of the experiment.

Results

TAA-induced hepatotoxicity indicated by a significant elevated in serum markers (Alanine aminotransferases (ALT), Aspartate aminotransferases (AST), and bilirubin), oxidative stress markers (Malondialdehyde (MDA), and Nitric oxide (NO)), and protein levels markers (NF-κB, and S100 calcium-binding protein A4 (S100A4)). Also, TAA decreased Nrf2, and increased GSK-3β genes expression. Histopathological alterations in the liver also appeared as a response to TAA injection. On the other hand VER and/or Cilo significantly prevented TAA-induced hepatotoxicity in rats through significantly decreased in ALT, AST, bilirubin, MDA, NO, NF-κB, and S100A4 protein levels. Also, they increased Nrf2 and decreased GSK-3β genes expression which caused improvement in the histopathological changes of the liver.

Conclusion

the addition of verapamil to cilostazol potentiated the hepatoprotective activity, and inhibited the progression of hepatotoxicity caused by TAA through the Nrf2/GSK-3β/NF-κBpathway and their activity on oxidative stress, inflammation, and NF-κB protein expression.
Scrub typhus seroprevalence from an eastern state of India: findings from the state-wide serosurvey
Authors: Parai Debaprasad , Pattnaik Matrujyoti , Kshatri Jaya Singh , Rout Usha Kiran , Peter Annalisha , Nanda Rashmi Ranjan , Sahoo Subrat Kumar , Mansingh Asit , Choudhary Hari Ram , Dash Girish Chandra , Praharaj Ira , Bhattacharya Debdutta , Pati Sanghamitra
Published: August 2022

Background

Scrub typhus is a mite-borne infectious disease caused primarily by the obligate intracellular bacteria Orientia tsutsugamushi, which is transmitted by chigger mites. The objective of this study was to determine the prevalence of scrub typhus among adults in Odisha, an eastern state of India.

Methods

A descriptive cross-sectional study was conducted to analyse 1840 serum samples from five districts (Khordha, Cuttack, Ganjam, Malkangiri and Sundargarh) of Odisha collected during 2020–2021. Both immunoglobulin G (IgG) and IgM antibodies against scrub typhus were tested using commercial enzyme-linked immunosorbent assay kits. Point estimates of the 95% confidence interval and adjusted odds ratio were calculated.

Results

Of 1840 participants, the prevalence of IgG positivity was 1034 (56.19%) and that of IgM was 523 (28.42%). The majority of participants were in the 18–45 y age group (53.7%). Cuttack had the highest IgG positivity (64.54%) and Malkangiri had the lowest (29.32%). The highest and lowest positivity for IgM were found in Malkangiri (40.84%) and Cuttack (25.30%), respectively.

Conclusions

With an increasing number of infections detected in the state, scrub typhus is emerging as a public health threat. Increasing awareness among the general public and healthcare professionals through health education campaigns regarding scrub typhus is essential. Early detection of the disease through the establishment of a laboratory surveillance system is required to control the transmission of scrub typhus.
Can helminth and malaria infections affect sex ratio at birth in sub-Saharan Africa? Ideas and hypothesis
Authors: Abdoli Amir
Published: August 2022

The sex ratio (ratio of boys to girls) at birth (SRB) is about 1.05 (about 105 males to 100 females) under normal conditions and could be an indicator for monitoring demographic changes. Generally, in comparison with female fetuses, the male fetus is biologically weaker and more vulnerable to prenatal events. SRB is influenced by various factors, such as maternal malnourishment. Remarkably, maternal malnourishment and less energy intake are pivotal factors for declining SRB in humans. As estimates, the SRB is below the normal range in sub-Saharan Africa (1.03) than the normal range (1.05). On the other hand, both malaria and helminth infections are hyperendemic in sub-Saharan Africa and both diseases are associated with maternal malnourishment. Hence, an important question arises, could declining SRB in sub-Saharan Africa be influenced by malaria and helminth infections? Cumulative evidence suggests that malaria and helminth infections could influence SRB by induction of maternal malnourishment. This hypothesis provides new ideas about the variation of SRB in some regions of the world where helminths and malaria are endemic.
Development of Screening Assays for Pathogen Virulence and Resistance to Phytophthora Root Rot and Wilting Complex in Raspberry
Authors: Sapkota Sanjib , Burlakoti Rishi R. , Dossett Michael , Punja Zamir K.
Published: August 2022

Phytophthora root rot and wilting complex (PRRW) of red raspberry, caused primarily by Phytophthora rubi, is an economically important disease in British Columbia (BC) and in raspberry producing regions globally. Reliable, rapid, and efficient screening methods are lacking for evaluating germplasm for potential disease resistance in raspberry breeding programs as well as for screening pathogen isolates for virulence. The objective of this study was to compare various screening methods for efficiency and rapidity in inducing symptoms of disease to identify the most suitable approach. We compared several intact plant root inoculation (IPRI) assays, detached stem assays, and an intact plant stem inoculation (IPSI) assay. A virulent isolate of P. rubi was inoculated in two commercial cultivars: ‘Chemainus’ (susceptible to PRRW) and ‘Cascade Bounty’ (moderately resistant to PRRW). For IPRI assays, days to first symptom development, plant wilt progression, and root assessment were recorded. For detached stem tissue and IPSI assays, days to first visible lesions and lesion size were assessed. Experiments were arranged in a completely randomized design with three replications in each experiment. Three IPRI assays produced reliable symptoms in both cultivars. Among the detached stem assays, a node inoculation method performed better than other methods. Detached stem assays are useful for rapid pathogenicity testing of P. rubi, whereas IPRI assays are better for screening germplasm for disease resistance. Overall, this study identified several assays that can be used for conducting studies on pathogen phenotypic diversity (pathogenicity and virulence tests) and screening raspberry cultivars, germplasm, and breeding materials for response to PRRW.
RETRACTED: Trehalose improves palmitic acid‐induced apoptosis of osteoblasts by regulating SIRT3‐medicated autophagy via the AMPK/mTOR/ULK1 pathway
Authors: Cao Lili , Zhou Siming , Qiu Xueshan , Qiu Shui
Published: August 2022

Accumulation of lipid substances decreased the activity of osteoblasts. Trehalose is a typical stress metabolite to form a protective membrane on cell surface which has been demonstrated to regulate lipid metabolism. This activity of Trehalose indicates the potential effect of osteoporosis treatment. Our study aimed to determine the therapeutic effect of Trehalose in high fat‐induced osteoporosis. We used palmitic acid (PA) to mimic the state of high fat and observed the apoptosis ratio of osteoblasts increased. After adding Trehalose, the apoptosis ratio decreased obviously. Autophagy is a regulatory means involved in the process of apoptosis. We detected the autophagy protein and found that the expression of Beclin‐1, Atg5, and LC3 II increased, and p62 decreased after Trehalose treatment. When adding an autophagy inhibitor (3‐MA), the expression of Beclin‐1, Atg5, and LC3 II decreased, and p62 increased. These results indicated autophagy was an important factor involved in the preventive effect of Trehalose in PA‐induced apoptosis. SIRT3 is a mitochondrial gene that can inhibit apoptosis, which has been reported to promote autophagy. We used SIRT3‐siRNA to silence the expression of SIRT3 and found the effect of Trehalose was counteracted. The apoptosis ratio increased and the expression of Beclin‐1, Atg5, and LC3 II decreased, p62 increased. Additionally, we also fed the mice with a high‐fat diet (HFD) and intragastrical Trehalose. The results showed that Trehalose could inhibit the bone mass loss with HFD. Our study revealed the effect and mechanism of Trehalose in the treatment of osteoporosis.