bluuebunny/crossref_metadata_2025 huggingface dataset:
Freezing from the inside: Ice nucleation in Escherichia coli and Escherichia coli ghosts by inner membrane bound ice nucleation protein InaZ
Authors: Kassmannhuber Johannes , Mauri Sergio , Rauscher Mascha , Brait Nadja , Schöner Lea , Witte Angela , Weidner Tobias , Lubitz Werner
Published: May 2020

Ice nucleation (IN) active bacteria such as Pseudomonas syringae promote the growth of ice crystals more effectively than any material known. Using the specialized ice nucleation protein (INP) InaZ, P. syringae—the well studied epiphytic plant pathogen—attacks plants by frost damage and, likewise fascinating, drives ice nucleation within clouds when airborne in the atmosphere by linkage to the Earth’s water cycle. While ice nucleation proteins play a tremendous role for life on the planet, the molecular details of their activity on the bacterial membrane surface are largely unknown. Bacterial ghosts (BGs) derived from Escherichia coli can be used as simplified model systems to study the mode of action of InaZ. In this work, the authors used BGs to study the role of InaZ localization on the luminal side of the bacterial inner membrane. Naturally, P. syringae INPs are displayed on the surface of the outer membrane; so in contrast, the authors engineered an N-terminal truncated form of inaZ lacking the transport sequence for anchoring of InaZ on the outer membrane. This construct was fused to N- and C-terminal inner membrane anchors and expressed in Escherichia coli C41. The IN activity of the corresponding living recombinant E. coli catalyzing interfacial ice formation of supercooled water at high subzero temperatures was tested by a droplet-freezing assay and surface spectroscopy. The median freezing temperature (T50) of the parental living E. coli C41 cells without INP was detected at −20.1 °C and with inner membrane anchored INPs at a T50 value between −7 and −9 °C, demonstrating that the induction of IN from the inside of the bacterium by inner membrane anchored INPs facing the luminal inner membrane side is very similar to IN induced by bacterial INPs located at the outer membrane. Bacterial ghosts derived from these different constructs showed first droplet freezing values between −6 and −8 °C, whereas E. coli C41 BGs alone without carrying inner membrane anchored INPs exhibit a T50 of −18.9 °C. Sum frequency generation spectroscopy showed structural ordered water at the BG/water interface, which increased close to the water melting point. Together, this indicates that the more efficient IN of INP-BGs compared to their living parental strains can be explained by the free access of inner membrane anchored INP constructs to ultrapure water filling the inner space of the BGs.
A protein kinase A–regulated network encodes short- and long-lived cellular memories
Authors: Jiang Yanfei , AkhavanAghdam Zohreh , Li Yutian , Zid Brian M. , Hao Nan
Published: May 2020

Yeast use different PKA-dependent mechanisms to encode short- and long-term memories of stresses.
Overcoming autoinhibition
Authors: Foley John F.
Published: May 2020

Conformational changes in the C-terminal region of PLC-β2 caused by G proteins release autoinhibition.
Northern-sourced water dominated the Atlantic Ocean during the Last Glacial Maximum
Authors: Pöppelmeier F. , Blaser P. , Gutjahr M. , Jaccard S.L. , Frank M. , Max L. , Lippold J.
Published: May 2020

Increased carbon sequestration in the ocean subsurface is commonly assumed to have been one of the main causes responsible for lower glacial atmospheric CO2 concentrations. Remineralized carbon must have been stored away from the atmosphere for thousands of years, yet the water mass structure accommodating such increased carbon storage continues to be debated. Here, we present new sediment-derived bottom-water neodymium isotope records that allow fingerprinting of water masses and provide a more complete picture of the Atlantic Meridional Overturning Circulation geometry during the Last Glacial Maximum. These results suggest that the vertical and meridional structure of the Atlantic water mass distribution only experienced minor changes since the last ice age. In particular, we find no compelling evidence supporting glacial southern-sourced water substantially expanding to shallower depths and farther into the Northern Hemisphere than today, which had been previously inferred from stable carbon isotope (δ13C) reconstructions. We argue that depleted δ13C values observed in the deep Northwest Atlantic do not necessarily indicate the presence of southern-sourced water. Instead, these values may represent a northern-sourced water mass with lower than modern preformed δ13C values that were further modified downstream by increased sequestration of remineralized carbon, facilitated by a more sluggish glacial deep circulation, corroborating previous evidence.
Patient-centred and economic effectiveness of a decision aid for patients with age-related cataract in China: study protocol of a randomised controlled trial
Authors: Zheng Yingfeng , Qu Bo , Jin Ling , Wang Chunxiao , Zhong Yuxin , He Mingguang , Liu Yizhi
Published: May 2020

Introduction

The need for cataract surgery is on the rise due to our ageing population and high demands for greater visual functioning. Although the majority of patients want to participate in a shared decision-making process, no decision aid has been available to improve the quality of decision. The present study aims to determine whether a decision aid increases informed decision about cataract surgery.

Methods and analysis

A parallel randomised controlled trial (772 participants) will be conducted. The decision aid will be implemented among patients with any age-related cataract in Yuexiu District, which is socioeconomically representative of a major metropolitan region in Southern China. Participants will be randomly assigned to receive either a patient decision aid or a traditional booklet, and they will complete three surveys: (1) baseline assessment before the intervention (time point (T)1), 2 weeks (T2) and 1 year (T3) after the intervention. The control group receives a traditional booklet with standard general information developed by the National Eye Institute to help patients understand cataract, whereas the intervention group receives a patient decision aid that includes not only the standard general information, but also the quantitative risk information on the possible outcomes of cataract surgery as well as value clarification exercise. The primary study outcome is the informed decision, the percentage of patients who have adequate knowledge and demonstrate consistency between attitudes and intentions. Secondary outcomes include perceived importance of cataract surgery benefits/harms, decision conflict and confidence, anticipated regret and booklet utilisation and acceptability at 2 weeks, and surgical rates and a cost–utility estimate of the decision aid at 1 year.

Ethics and dissemination

Ethics approval was obtained from the Ethics Committee of Zhongshan Ophthalmic Center (reference number: 2019KYPJ090). Results will be published in peer-reviewed journals and presented at scientific meetings for academic audiences.

Trial registration number

NCT03992807.
Qualitative accounts from Syrian mental health professionals: shared realities in the context of conflict and forced displacement
Authors: Hamid Aseel , Scior Katrina , Williams Amanda C de C
Published: May 2020

Objectives

To explore the impact of the provision of care of forcibly displaced Syrian mental health professionals (MHPs) to Syrian clients in the community given shared experiences and backgrounds with clients.

Design

A qualitative study using thematic analysis of in-depth semistructured interviews to explore shared realities, self-disclosure and the impact of providing therapy.

Setting

Syrian MHPs operating in Gaziantep and Istanbul, Turkey, were interviewed.

Participants

Sixteen forcibly displaced Syrian MHPs (eight male, eight female) aged between 24 and 54 years (M=35, SD=8.3) who provided care to the displaced Syrian community in Turkey.

Results

All workers described having a shared reality with their clients as helpful in therapy and a smaller proportion described it as a vulnerability. All described their work with Syrian clients as fulfilling and most described it as distressing. Participants referred to self-care,supervision, peer-support and personal therapy as a means to cope.

Conclusions

This study provides the first insight into the shared experiences of the ongoing trauma, loss and violations resulting from the ongoing Syrian conflict from the perspective of Syrian MHPs, adding to the literature of the professional issues and ethical duty to protect health workers in conflict settings.
Cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) for chronic insomnia disorder (‘CANSLEEP’ trial): protocol for a randomised, placebo-controlled, double-blinded, proof-of-concept trial
Authors: Suraev Anastasia , Grunstein Ronald R , Marshall Nathaniel S , D'Rozario Angela L , Gordon Christopher J , Bartlett Delwyn J , Wong Keith , Yee Brendon J , Vandrey Ryan , Irwin Chris , Arnold Jonathon C , McGregor Iain S , Hoyos Camilla M
Published: May 2020

Introduction

Insomnia is a highly prevalent and costly condition that is associated with increased health risks and healthcare utilisation. Anecdotally, cannabis use is frequently reported by consumers to promote sleep. However, there is limited research on the effects of cannabis on sleep and daytime function in people with insomnia disorder using objective measures. This proof-of-concept study will evaluate the effects of a single dose of an oral cannabis-based medicine on sleep and daytime function in participants with chronic insomnia disorder.

Methods and analysis

A randomised, crossover, placebo-controlled, single-dose study design will be used to test the safety and efficacy of an oral oil solution (‘ETC120’) containing 10 mg Δ9-tetrahydrocannabinol (THC) and 200 mg cannabidiol (CBD) in 20 participants diagnosed with chronic insomnia disorder. Participants aged 35–60 years will be recruited over an 18-month period commencing August 2019. Each participant will receive both the active drug and matched placebo, in a counterbalanced order, during two overnight study assessment visits, with at least a 1-week washout period between each visit. The primary outcomes are total sleep time and wake after sleep onset assessed via polysomnography. In addition, 256-channel high-density electroencephalography and source modelling using structural brain MRI will be used to comprehensively examine brain activation during sleep and wake periods on ETC120 versus placebo. Next-day cognitive function, alertness and simulated driving performance will also be investigated.

Ethics and dissemination

Ethics approval was received from Bellberry Human Research Ethics Committee (2018-04-284). The findings will be disseminated in a peer-reviewed open-access journal and at academic conferences.

Trial registration number

ANZCTRN12619000714189.
Patients’ views on involving general practice in bowel cancer screening: a South Australian focus group study
Authors: Brown Lynsey , Moretti Cecilia , Roeger Leigh , Reed Richard
Published: May 2020

Objectives

To explore patients’ experiences of bowel cancer screening and its promotion, and perspectives on possible input from general practice for improving screening rates.

Design

Qualitative focus group study underpinned by a phenomenological approach.

Setting

Three general practice clinics in metropolitan South Australia.

Participants

Thirty active general practice patients, aged 50–74 years (60% female) who were eligible for the National Bowel Cancer Screening Program.

Findings

Factors affecting screening were described, with particular concerns regarding the nature of the test, screening process and culture. There were mixed views on the role for general practice in bowel cancer screening; some participants appreciated the current process and viewed screening as out of scope of primary care services, while others were in support of general practice involvement. Roles for general practice were proposed that comprised actions across the continuum from providing information through to reminders and the provision and collection of screening kits. With a view that multifaceted strategies are required to encourage participation, community-based solutions were suggested that centred on improving screening culture and education.

Conclusions

There was a view among participants that general practice could play a useful role in supporting the uptake of the National Bowel Cancer Screening Program, however participants saw a need for multiple strategies at different levels and under different jurisdictions.
Association between obesity-related anthropometric indices and multimorbidity among older adults in Shandong, China: a cross-sectional study
Authors: Zhang Jiao , Xu Lingzhong , Li Jiajia , Sun Long , Qin Wenzhe
Published: May 2020

Objectives

Whether the association between obesity-related anthropometric indices and multimorbidity differs by age among Chinese older adults (aged 65+) is unclear. We aimed to investigate the association between body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) with multimorbidity among the young-old (aged 65–79) and old-old (aged 80+) adults.

Design

Cross-sectional population-based study.

Setting

Shandong province on the eastern coast of China.

Participants

5493 subjects aged 65 years or above.

Measurements

Details on sociodemographics, lifestyle characteristics and chronic conditions were collected using a structured questionnaire. The respondents were assessed with anthropometric measurements including height, weight, WC, hip circumference.

Results

The overall prevalence of multimorbidity in older adults (aged 65+) was 35.2%. The BMI-obesity, WC-obesity and WHR-obesity rates were 7.4%, 57.5% and 80.4%, respectively. In the young-old adults (aged 65–79), the likelihood of multimorbidity was more than two times higher among the BMI-obese than the BMI-normal population (OR 2.08, 95% CI 1.66 to 2.60). Similar but less strong associations were found for the WC-obese and WHR-obese young-old population (OR 1.60, 95% CI 1.42 to 1.81; OR 1.31, 95% CI 1.10 to 1.56, respectively). For the old-old group (aged 80+), the BMI-obese, WC-obese and WHR-obese had a higher likelihood of having multimorbidity compared with the normal weight category (OR 2.10, 95% CI 0.96 to 4.57; OR 1.75, 95% CI 1.21 to 2.54; OR 2.15, 95% CI 1.18 to 3.93, respectively).

Conclusion

BMI-obesity, WC-obesity and WHR-obesity were associated with a greater risk of multimorbidity, and the associations were different between the young-old and the old-old adults. These age differences need to be considered in assessing healthy body weight in old age. These findings may be vital for public health surveillance, prevention and management strategies for multimorbidity in older adults.
Resuming elective surgical services in times of COVID-19 infection
Authors: Coimbra Raul , Edwards Sara , Coimbra Bruno Cammarota , Tabuenca Arnold
Published: May 2020

The consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been devastating to the healthcare system.

As the positive effects of social distancing, mandatory masking, and societal lockdown on the spread of the disease and its incidence in the community were documented, societal and financial pressures mounted worldwide, prompting efforts to “re-open” countries, states, communities, businesses, and schools. The same happened with hospital, which had to start developing strategies to resume elective surgery activities. This manuscript describes the pre-requisites as well as the strategies for resuming surgical activity, be it in the outpatient or inpatient setting.
Evaluating the presence of human pathogens in commercially frozen, biologically appropriate raw pet food sold in Italy
Authors: Bottari Benedetta , Bancalari Elena , Barera Annalisa , Ghidini Sergio , Gatti Monica
Published: May 2020

Background

Biologically appropriate raw food (BARF) diet is becoming more and more popular among pet owners in Europe. However, there are documented microbiological risks associated with raw feeding, and this study aimed to determine the presence of human pathogens in commercially frozen BARF products sold in Italy.

Methods

Salmonella species, Escherichia coli O157:H7, Listeria monocytogenes and Campylobacter species were identified. The general microbiological quality of BARF products and hygiene were also evaluated. Sample size was limited and therefore the study may not be representative of a larger sample.

Results

None of the tested samples showed total bacterial count (TBC) higher than the limit set to consider a sample unacceptable. However, 14 out of 21 samples showed TBC higher than the limit set to consider a sample marginally acceptable. A high percentage of samples were contaminated by the aforementioned pathogens, highlighting the need for pet owners to be aware of the risks of this feeding strategy both to themselves and to their pets.

Conclusions

Considering that BARF diet meals can be prepared at home using the hands, as well as tools and spaces that could be shared, guidelines on safer handling of these pet food products should be recommended by veterinarians and nutritionists.
Catalytic Lewis and Brønsted acid syn-diastereoselective benzylic substitutions of α-hydroxy-β-nitro- and α-hydroxy-β-azido-alkyl arenes
Authors: Hensienne Raphaël , Cusson Jean-Philippe , Chénard Étienne , Hanessian Stephen
Published: May 2020

A series of alkyl and alkenyl p-methoxy arenes containing α,β-disubstituted diamino and amino alcohol groups were synthesized from β-nitro and β-azido benzylic alcohols in the presence of AuCl3 as catalyst. The formation of predominantly syn-disubstituted products were rationalized on the basis of mechanistic considerations and transition state models relying on A1,3-allylic strain. The products could have utility in the design of medicinally relevant compounds and as chiral ligands for asymmetric catalysis. A new synthesis of (+)-sertraline (Zoloft) was achieved.
Control of annual ryegrass with spring-applied herbicides prior to seeding corn
Authors: Soltani Nader , Shropshire Christy , Sikkema Peter H.
Published: May 2020

Four field experiments were conducted over a 2 yr period (2017 and 2018) in Ontario to determine the control of annual ryegrass (ARG) seeded in the fall of 2016 and 2017 (as a cover crop) with spring-applied glyphosate alone and in a tankmixure with clethodim, fluazifop-P-butyl, quizalofop-P-butyl, sethoxydim, or saflufenacil prior to seeding glyphosate-resistant corn. The doses of glyphosate needed to provide 50%, 80%, and 90% control of ARG were 439, 1757, and >2700 g a.e. ha−1 at 3 wk after treatment application (WAA); 526, 2105, and >2700 g a.e. ha−1 at 4 WAA; and 703, >2700, and >2700 g a.e. ha−1 at 6 WAA, respectively. Glyphosate (1350 g a.e. ha−1) controlled ARG 27%, 61%, 77%, 72%, and 68% at 1, 2, 3, 4, and 6 WAA, respectively. The tankmix of glyphosate (1350 a.e. ha−1) with clethodim (30 g a.i. ha−1), fluazifop-P-butyl (125 g a.i. ha−1), quizalofop-P-ethyl (36 g a.i. ha−1), sethoxydim (150 g a.i. ha−1), or saflufenacil (25 g a.i. ha−1) controlled ARG as much as 82%, 79%, 82%, 84%, and 81%, respectively. ARG control with the tankmixes of glyphosate (1350 a.e. ha−1) with the Group 1 herbicides evaluated increased corn yield as much as 66%. Additionally, reduced ARG interference with the tankmix of glyphosate (1350 a.e. ha−1) +saflufenacil (25 g a.i. ha−1) increased corn yield 69%. The best control of ARG was achieved with high doses of glyphosate alone and glyphosate (1350 g a.e. ha−1) tankmixed with a Group 1 herbicide or saflufenacil.
Impact of weed management practices on soil biological activity in corn and soybean field crops in Québec (Canada)
Authors: Samson-Brais Émile , Lucotte Marc , Moingt Matthieu , Tremblay Gilles , Paquet Serge
Published: May 2020

Repeated applications and combination of glyphosate-containing herbicides (GCH) with other herbicides are two weed management practices (WMP) used to compensate for GCH decreasing efficiency impacts in field crops. These practices may have serious impacts on soil functions because GCH affect soil biota and soil biological activity (SBA). Two field experiments, one with corn and one with soybean crops, were conducted during one growing season. SBA indicators, soil respiration (SR) and fluorescein diacetate (FDA) hydrolysis, were measured at two sampling times following six WMP. These WMP included one or two GCH applications (GCH alone or combined with other herbicides), applications of other herbicides only and mechanical weeding. WMP did not affect FDA neither for corn or soybean at either sampling times. In contrast, WMP affected SR in corn fields at both sampling times and SR in soybean field at the first sampling time. Repeating GCH applications and combining different herbicides led to lower SR, suggesting that these practices decreased SBA, whilst one single GCH application presented higher SR, suggesting that this practice stimulated SBA. Our study demonstrates that using GCH in combination with other herbicides or in multiple applications affects SBA in field conditions. Affecting soil functions and carbon cycle do bear serious weed management implications, and the choice of WMP should be taken into consideration to minimize their impacts on SBA for field crops sustainability.
Compex: a cubic germanium detector
Authors: Såmark-Roth A. , Cox D. M. , Eberth J. , Golubev P. , Rudolph D. , Sarmiento L. G. , Tocabens G. , Ginsz M. , Pirard B. , Quirin P.
Published: May 2020

The Compex detector is an electrically cooled, composite germanium detector that uses four coaxial, cubic-shaped, single-encapsulated germanium crystals. This novel detector allows for new heights in photon detection efficiency in decay spectroscopy setups using box-shaped vacuum chambers. Its spectroscopic performance and detection efficiency is evaluated by means of source measurements. Motivated by Compex’s unique cubic germanium crystals, the Lund scanning system has been developed. The constructed system is used to characterise the response as a function of interaction position within a Compex crystal. Sensitivity across the front face, pulse shapes, and rise times have been analysed. Future development and applications of the Compex detector are discussed.
Mathematical prediction of the time evolution of the COVID-19 pandemic in Italy by a Gauss error function and Monte Carlo simulations
Authors: Ciufolini Ignazio , Paolozzi Antonio
Published: May 2020

In this paper are presented mathematical predictions on the evolution in time of the number of positive cases in Italy of the COVID-19 pandemic based on official data and on the use of a function of the type of a Gauss error function, with four parameters, as a cumulative distribution function. We have analyzed the available data for China and Italy. The evolution in time of the number of cumulative diagnosed positive cases of COVID-19 in China very well approximates a distribution of the type of the error function, that is, the integral of a normal, Gaussian distribution. We have then used such a function to study the potential evolution in time of the number of positive cases in Italy by performing a number of fits of the official data so far available. We then found a statistical prediction for the day in which the peak of the number of daily positive cases in Italy occurs, corresponding to the flex of the fit, that is, to the change in sign of its second derivative (i.e., the change from acceleration to deceleration), as well as of the day in which a substantial attenuation of such number of daily cases is reached. We have also analyzed the predictions of the cumulative number of fatalities in both China and Italy, obtaining consistent results. We have then performed 150 Monte Carlo simulations to have a more robust prediction of the day of the above-mentioned peak and of the day of the substantial decrease in the number of daily positive cases and fatalities. Although official data have been used, those predictions are obtained with a heuristic approach since they are based on a statistical approach and do not take into account either a number of relevant issues (such as number of daily nasopharyngeal swabs, medical, social distancing, virological and epidemiological) or models of contamination diffusion.
Discriminative Analysis of Symptom Severity and Ultra-High Risk of Schizophrenia Using Intrinsic Functional Connectivity
Authors: Wang Lubin , Li Xianbin , Zhu Yuyang , Lin Bei , Bo Qijing , Li Feng , Wang Chuanyue
Published: May 2020

Past studies have consistently shown functional dysconnectivity of large-scale brain networks in schizophrenia. In this study, we aimed to further assess whether multivariate pattern analysis (MVPA) could yield a sensitive predictor of patient symptoms, as well as identify ultra-high risk (UHR) stage of schizophrenia from intrinsic functional connectivity of whole-brain networks. We first combined rank-based feature selection and support vector machine methods to distinguish between 43 schizophrenia patients and 52 healthy controls. The constructed classifier was then applied to examine functional connectivity profiles of 18 UHR individuals. The classifier indicated reliable relationship between MVPA measures and symptom severity, with higher classification accuracy in more severely affected schizophrenia patients. The UHR subjects had classification scores falling between those of healthy controls and patients, suggesting an intermediate level of functional brain abnormalities. Moreover, UHR individuals with schizophrenia-like connectivity profiles at baseline presented higher rate of conversion to full-blown illness in the follow-up visits. Spatial maps of discriminative brain regions implicated increases of functional connectivity in the default mode network, whereas decreases of functional connectivity in the cerebellum, thalamus and visual areas in schizophrenia. The findings may have potential utility in the early diagnosis and intervention of schizophrenia.
BONE ORTHOTROPIC REMODELING AS A THERMODYNAMICALLY-DRIVEN EVOLUTION
Authors: MARTIN M. , LEMAIRE T. , HAIAT G. , PIVONKA P. , SANSALONE V.
Published: May 2020

In this paper, we present and discuss a model of bone remodeling set up in the framework of the theory of generalized continuum mechanics which was first introduced by DiCarlo et al. [Sur le remodelage des tissus osseux anisotropes, Comptes Rendus Mécanique 334(11):651–661, 2006]. Bone is described as an orthotropic body experiencing remodeling as a rotation of its microstructure. Thus, the complete kinematic description of a material point is provided by its position in space and a rotation tensor describing the orientation of its microstructure. Material motion is driven by energetic considerations, namely by the application of the Clausius–Duhem inequality to the microstructured material. Within this framework of orthotropic remodeling, some key features of the remodeling equilibrium configurations are deduced in the case of homogeneous strain or stress loading conditions. First, it is shown that remodeling equilibrium configurations correspond to energy extrema. Second, stability of the remodeling equilibrium configurations is assessed in terms of the local convexity of the strain and complementary energy functionals hence recovering some classical energy theorems. Eventually, it is shown that the remodeling equilibrium configurations are not only highly dependent on the loading conditions, but also on the material properties.
Industry 4.0 in a Small Commodity-Based Economy: A Vehicle for Stimulating Innovation
Authors: King Graham S. , Rameshwar Jason R. , Syan Chanan S.
Published: May 2020

Innovation is fundamental for companies to exploit changes in their environment and maintain a competitive advantage. Access to information and the ability to quickly utilise available resources are key enablers for in-company innovation. Both of these are elements associated with Industry 4.0, which can now be identified as a facilitator of innovation. The Industry 4.0 framework integrates evolutionary advances in manufacturing, production technologies, information technology, Internet of Things (IoT), distributed processing power, and visualization tools, which facilitate organizations to more effectively create enhanced value propositions for their customers, encouraging innovation in processes and products. Three local firms are analyzed, and opportunities for innovation are clearly identified in the process of transitioning to Industry 4.0 through reconfigured value chains; the creation of a cluster to facilitate the development of innovative cloud-based solutions; and product configurator and an augmented reality interactive display.
Better Classifier Calibration for Small Datasets
Authors: Tuomo Alasalmi , Suutala Jaakko , Röning Juha , Koskimäki Heli
Published: May 2020

Classifier calibration does not always go hand in hand with the classifier’s ability to separate the classes. There are applications where good classifier calibration, i.e., the ability to produce accurate probability estimates, is more important than class separation. When the amount of data for training is limited, the traditional approach to improve calibration starts to crumble. In this article, we show how generating more data for calibration is able to improve calibration algorithm performance in many cases where a classifier is not naturally producing well-calibrated outputs and the traditional approach fails. The proposed approach adds computational cost but considering that the main use case is with small datasets this extra computational cost stays insignificant and is comparable to other methods in prediction time. From the tested classifiers, the largest improvement was detected with the random forest and naive Bayes classifiers. Therefore, the proposed approach can be recommended at least for those classifiers when the amount of data available for training is limited and good calibration is essential.
Still No Substantial Evidence to Use Prophylactic Antibiotic at Operative Vaginal Delivery: Systematic Review and Meta-Analysis
Authors: Berhan Yifru , Kirba Sisay , Gebre Achamyelesh
Published: May 2020

Background. Postpartum maternal infection is still a common problem worldwide, mainly due to obstetric risk factors. The use of prophylactic antibiotic at operative vaginal delivery (OVD), taking it as a standalone risk factor, has been controversial. The purpose of this review was to rigorously evaluate the association of OVD with postpartum infection and shed light on such highly controversial issue. Methods. A computer-based literature search was done mainly in the databases of PUBMED, HINARI health research, and the Cochrane library. Systematic review and meta-analysis were done by including 14 articles published between 1990 and August 2019. Results. The average absolute risk of postpartum infection at OVD from seven large cohort studies was 1%. Few studies showed a weak association of OVD with postpartum infection without being adjusted to perineal wound, but the pooled meta-analysis showed statistically significant association with non-OVD. In the included randomized trial, 97% of the study participants had perineal wound for whom repairs were performed; the risks of maternal infection and perineal wound breakdown were comparable, and maternal infections other than perineal wound infection did not show significant difference between prophylactic antibiotic and placebo groups. The majority of included studies demonstrated a strong association of postpartum infection and perineal wound dehiscence with episiotomy and perineal tear. Conclusion. Both the relative and absolute risks of postpartum infection at OVD are extremely low unless accompanied by episiotomy and 3rd/4tht degree perineal tear. From previous studies, there is no substantial evidence to use prophylactic antibiotic at OVD, but episiotomy and perineal tear.
Associations of Small Fiber Neuropathy with Geriatric Nutritional Risk Index and Arterial Stiffness in Hemodialysis
Authors: Kuo Mei-Chuan , Huang Jiun-Chi , Wu Pei-Yu , Mai Hsiu-Chin , Chen Szu-Chia , Chiu Yi-Wen , Chang Jer-Ming , Chen Hung-Chun
Published: May 2020

Background. Peripheral neuropathy is a common neurological complication in uremic patients, and quantitative sensory testing (QST) is effective for diagnosis of small fiber neuropathy. Malnutrition and arterial stiffness are prevalent in patients undergoing hemodialysis (HD). The associations of small fiber neuropathy with nutritional status and arterial stiffness remain uncertain in maintenance HD patients. Methods. A total of 152 HD patients were included. Geriatric nutritional risk index (GNRI), an indicator of nutritional status, was calculated by serum albumin and actual and ideal body weight. Arterial stiffness was defined as brachial-ankle pulse wave velocity baPWV>1400 cm/s. Small fiber neuropathy was assessed by an abnormal QST threshold of cold and warm sensation in patients’ hands or feet. Multivariate forward logistic regression analysis was performed to examine the associations among abnormal QST threshold, GNRI, and arterial stiffness. Results. baPWV and prevalence of abnormal QST threshold were significantly higher in diabetic patients. Multivariate logistic analyses revealed that older age (OR, 1.081; 95% CI, 1.026–1.139, p=0.003) and male gender (OR, 4.450; 95% CI, 1.250–15.836, p=0.021) were associated with abnormal warm threshold of hands. Furthermore, diabetes (OR, 3.966; 95% CI, 1.351–11.819, p=0.012) and lower GNRI (per 1 unit increase, OR, 0.935, 95% CI, 0.887–0.985, p=0.012) were associated with abnormal cold threshold of feet. Arterial stiffness (OR, 5.479, 95% CI, 1.132–22.870, p=0.020) and higher calcium-phosphorus product (OR, 1.071, 95% CI, 1.013–1.132, p=0.015) were associated with abnormal warm threshold of feet. Conclusions. Lower GNRI and arterial stiffness were significantly associated with small fiber neuropathy in patients undergoing HD. Malnutrition risk and vascular factors might play important roles in small fiber neuropathy among patients undergoing HD.
Analysis of Acrylamide in Dried Blood Spots of Lung Cancer Patients by Ultrahigh-Performance Liquid Chromatography Tandem Mass Spectrometry
Authors: Harahap Yahdiana , Elysia Camilla , Starlin Zenshiny , Jayusman Achmad Mulawarman
Published: May 2020

Acrylamide (AA) is a carcinogenic substance found in food, cigarette smoke and in an environment exposed to acrylamide. This study aims to analyze AA levels in dried blood spot (DBS) samples of lung cancer patients with smoking record, without smoking record, and also in the negative blank. Analysis of AA levels was determined by liquid chromatography tandem mass spectrometry (LC-MS/MS) and DBS extraction using protein precipitation techniques. Mass detection was done using positive electron spray ionization (ESI) and multiple reaction monitoring (MRM) type with m/z values of 71.99 > 55.23 for acrylamide and m/z 260.16 > 116.04 for propranolol as the internal standard. AA levels in lung cancer patients with smoking record is in the range of 4.670 μg/mL to 11.986 μg/mL. AA levels in lung cancer patients without smoking record is in the range of 2.041 μg/mL to 12.702 μg/mL. Data on AA levels on negative blanks is in the range of 2.72 μg/mL to 3.51 μg/mL. The results of the independent sample t-test (p>0.05) showed that AA levels in patients with smoking record and those without smoking record did not differ significantly. Then, the Mann-Whitney test was performed between the lung cancer group and the negative blank group and a significant difference was found between the two groups (p<0.05).
Mechanisms of Floor Heave in Roadways Adjacent to a Goaf Caused by the Fracturing of a Competent Roof and Controlling Technology
Authors: Liu Shuaigang , Bai Jianbiao , Wang Xiangyu , Wu Bowen , Wu Wenda
Published: May 2020

In traditional sequential single-wing mining practices, one-entry longwall mining systems make it challenging to efficiently and smoothly transfer mining equipment during a continuous mining sequence. In two-entry longwall systems, the headgate of the current panel and the tailgate of the next panel are excavated parallel to one another, effectively creating space for the transfer of mining equipment. The tailgate of the panel, however, is subjected to high-mining-induced stresses, causing severe floor heave, which seriously affects the efficiency of coal production. In this paper, field measurements and numerical simulation methods are used to reveal the mechanism of floor heave induced by the rupture and instability of a competent roof. The results show that the positional relationship between the adjacent tailgate and the longwall face is divided into three stages. Throughout the three stages, the area in which the coal pillar is not horizontally displaced moves from the center of the pillar to the goaf, and the area of peak vertical stress within the coal pillar shifts from the center of the pillar to the side nearest to the tailgate. Field studies suggest that the proposed technologies can effectively control floor heave in the tailgates of two-entry longwall mining systems.
A Comprehensive Biological and Clinical Perspective Can Drive a Patient-Tailored Approach to Multiple Myeloma: Bridging the Gaps between the Plasma Cell and the Neoplastic Niche
Authors: Solimando Antonio Giovanni , Vacca Angelo , Ribatti Domenico
Published: May 2020

There is a broad spectrum of diseases labeled as multiple myeloma (MM). This is due not only to the composite prognostic risk factors leading to different clinical outcomes and responses to treatments but also to the composite tumor microenvironment that is involved in a vicious cycle with the MM plasma cells. New therapeutic strategies have improved MM patients’ chances of survival. Nevertheless, certain patients’ subgroups have a particularly unfavorable prognosis. Biological stratification can be subdivided into patient, disease, or therapy-related factors. Alternatively, the biological signature of aggressive disease and dismal therapeutic response can promote a dynamic, comprehensive strategic approach, better tailoring the clinical management of high-risk profiles and refractoriness to therapy and taking into account the role played by the MM milieu. By means of an extensive literature search, we have reviewed the state-of-the-art pathophysiological insights obtained from translational investigations of the MM-bone marrow microenvironment. A good knowledge of the MM niche pathophysiological dissection is crucial to tailor personalized approaches in a bench-bedside fashion. The discussion in this review pinpoints two main aspects that appear fundamental in order to gain novel and definitive results from the biology of MM. A systematic knowledge of the plasma cell disorder, along with greater efforts to face the unmet needs present in MM evolution, promises to open a new therapeutic window looking out onto the plethora of scientific evidence about the myeloma and the bystander cells.
Efficacy and Safety of Bushenjiangya‐Optimized Granule for Left Ventricular Diastolic Dysfunction in Hypertensive Patients: A Double‐Blind, Randomized, Placebo‐Controlled Trial
Authors: Gao Qun , Cui Xiao-yun , Dong Fei , Fan Wen-ying , Li Pin-hui , Liu Jing , Lu Jin-jin , Meng Yan , Qu Wen-bai , Zhou Kun , Lin Qian
Published: May 2020

Objective. The study aimed to evaluate the efficacy and safety of Bushenjiangya‐optimized (BSJYO) granule on left ventricular diastolic dysfunction (LVDD) in hypertensive (HTN) patients. Methods. 120 patients diagnosed with HTN plus LVDD were randomly assigned to the BSJYO granule group and placebo group, and all patients received basal western medicine (WM) treatment. After eight weeks of treatment, we evaluated echocardiography, traditional Chinese medicine (TCM) syndromes, 24‐hour ambulatory blood pressure, liver and kidney functions, and adverse events. Major adverse cardiovascular events (MACEs) were collected at 6‐month follow‐up. Results. Compared with pretreatment, E/Ea (Doppler‐derived index of filling pressure and worsening LVDD) significantly decreased significantly after 8 weeks of treatment in the BSJYO granule plus basal WM group (10.52 ± 1.87 vs. 9.49 ± 1.49, P < 0.01), alongside reductions in significantly effective response (SER), effective response (ER), and total effective response (TER = SER + ER) in TCM symptom scores (21.59% vs. 71.70%, P < 0.01). There were no differences between treatment groups in kidney and liver function, early adverse events, or MACE. Conclusion. BSJYO granule plus basal WM is an effective and safe therapy for HTN patients with LVDD.
EGFR Blockade Reverts Resistance to KRASG12C Inhibition in Colorectal Cancer
Authors: Amodio Vito , Yaeger Rona , Arcella Pamela , Cancelliere Carlotta , Lamba Simona , Lorenzato Annalisa , Arena Sabrina , Montone Monica , Mussolin Benedetta , Bian Yu , Whaley Adele , Pinnelli Marika , Murciano-Goroff Yonina R. , Vakiani Efsevia , Valeri Nicola , Liao Wei-Li , Bhalkikar Anuja , Thyparambil Sheeno , Zhao Hui-Yong , de Stanchina Elisa , Marsoni Silvia , Siena Salvatore , Bertotti Andrea , Trusolino Livio , Li Bob T. , Rosen Neal , Di Nicolantonio Federica , Bardelli Alberto , Misale Sandra
Published: May 2020

Most patients with KRASG12C–mutant non–small cell lung cancer (NSCLC) experience clinical benefit from selective KRASG12C inhibition, whereas patients with colorectal cancer bearing the same mutation rarely respond. To investigate the cause of the limited efficacy of KRASG12C inhibitors in colorectal cancer, we examined the effects of AMG510 in KRASG12C colorectal cancer cell lines. Unlike NSCLC cell lines, KRASG12C colorectal cancer models have high basal receptor tyrosine kinase (RTK) activation and are responsive to growth factor stimulation. In colorectal cancer lines, KRASG12C inhibition induces higher phospho-ERK rebound than in NSCLC cells. Although upstream activation of several RTKs interferes with KRASG12C blockade, we identify EGFR signaling as the dominant mechanism of colorectal cancer resistance to KRASG12C inhibitors. The combinatorial targeting of EGFR and KRASG12C is highly effective in colorectal cancer cells and patient-derived organoids and xenografts, suggesting a novel therapeutic strategy to treat patients with KRASG12C colorectal cancer.

Significance:

The efficacy of KRASG12C inhibitors in NSCLC and colorectal cancer is lineage-specific. RTK dependency and signaling rebound kinetics are responsible for sensitivity or resistance to KRASG12C inhibition in colorectal cancer. EGFR and KRASG12C should be concomitantly inhibited to overcome resistance to KRASG12C blockade in colorectal tumors.

See related commentary by Koleilat and Kwong, p. 1094.

This article is highlighted in the In This Issue feature, p. 1079
Response Rate and Prognostic Impact of Salvage Chemotherapy after Nivolumab in Patients with Advanced Gastric Cancer
Authors: Arigami Takaaki , Matsushita Daisuke , Okubo Keishi , Yanagita Shigehiro , Ehi Katsuhiko , Sasaki Ken , Noda Masahiro , Kita Yoshiaki , Mori Shinichiro , Kurahara Hiroshi , Uenosono Yoshikazu , Ishigami Sumiya , Natsugoe Shoji
Published: May 2020

Objective: Nivolumab is recommended as a third-line treatment in patients with unresectable advanced or recurrent gastric cancer. Although recent studies have demonstrated the prognostic impact of salvage chemotherapy after immune checkpoint inhibitors in several malignancies, its clinical significance remains unclear in patients with gastric cancer. This study aimed to investigate tumor response to subsequent chemotherapy after nivolumab in patients with advanced gastric cancer and assess the prognostic effect of salvage chemotherapy. Methods: We retrospectively enrolled 31 patients with unresectable advanced or recurrent gastric cancer receiving nivolumab. Results: Twenty-two and nine patients received nivolumab as third-line and fourth- to sixth-line treatments, respectively. The objective response rate (ORR) and disease control rate (DCR) to nivolumab were 20.0% (4/20) and 55.0% (11/20), respectively. Eleven patients received salvage chemotherapy after nivolumab. The ORR and DCR to salvage chemotherapy were 37.5% (3/8) and 75.0% (6/8), respectively. The median progression-free survival and overall survival following salvage chemotherapy were 285 and 360 days, respectively. Conclusion: Our preliminary study indicates that nivolumab exposure may enhance subsequent chemosensitivity in patients with advanced gastric cancer.
Short-Term Psychodynamic Psychotherapy for Functional Somatic Disorders: A Meta-Analysis of Randomized Controlled Trials
Authors: Abbass Allan , Town Joel , Holmes Hannah , Luyten Patrick , Cooper Angela , Russell Leo , Lumley Mark A. , Schubiner Howard , Allinson Jenny , Bernier Denise , De Meulemeester Celine , Kroenke Kurt , Kisely Steve
Published: May 2020

Introduction: Functionalsomatic disorders (FSD) are common and costly, thereby driving the need for the development of effective brief treatment options. Short-term psychodynamic psychotherapy (STPP) is one candidate treatment method. Objective: To review and meta-analyze, where possible, randomized controlled trials (RCTs) of STPP for FSD. Methods: Following a systematic search of the literature, we performed a meta-analysis of available RCT groups to determine the effects of STPP on a range of outcomes after treatment, and medium- and long-term follow-ups. Results: In meta-analyses of 17 RCTs, STPP significantly outperformed minimal treatment, treatment as usual, or waiting list controls on somatic symptom measures at all time frames, with small to large magnitude effect sizes. Descriptive reviews of 5 RCTs suggest that STPP performed at least as well as other bona fide psychological therapies. Limitations of this meta-analysis include small samples of studies and possible publication bias. Conclusions: STPP is a valid treatment option for diverse FSD conditions resulting in somatic symptom reductions that persist over time. STPP should be included in FSD treatment guidelines.
Extracorporeal Photopheresis in Graft-versus-Host Disease
Authors: Drexler Beatrice , Buser Andreas , Infanti Laura , Stehle Gregor , Halter Joerg , Holbro Andreas
Published: May 2020

Background and Summary: Extracorporeal photopheresis (ECP) is a leukapheresis-based procedure used in the therapy of acute and chronic graft-versus-host disease (aGvHD, cGvHD) and other diseases. Based on the substantial efficacy and the excellent safety profile in the absence of immunosuppression ECP has established itself as a major treatment form for steroid-refractory GvHD. Here we review the current literature on ECP as a treatment option for patients with aGvHD as well as cGvHD. Key Messages: ECP is a well-established second-line therapy for cGvHD. Its role in the treatment of aGvHD is less clear but also points towards an effective second-line therapy option. In the future ECP could play a role in the prevention of GvHD. More experimental and randomized controlled trials are needed to define the best patient selection criteria, settings, and therapy regimens for GvHD.
Enumeration of the minimal node cutsets based on necessary minimal paths
Authors: Lamalem Yasser , Housni Khalid , Mbarki Samir
Published: May 2020

Reliability evaluation is an important research field for a complex network. The most popular methods for such evaluation often use Minimal Cuts (MC) or Minimal paths (MP). Nonetheless, few algorithms address the issue of the enumeration of all minimal cut sets from the source node s to the terminal node t when only the nodes of the network are subject to random failures. This paper presents an effective algorithm which enumerates all minimal node cuts sets of a network. The proposed algorithm runs in two steps: The first one is used to generate a subset of paths, called necessary minimal paths, instead of all minimal paths. Whereas, the second step stands to build all minimal cutsets from the necessary minimal paths.