bluuebunny/crossref_metadata_2025 huggingface dataset:
Correction to: Evaluating the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in severely ill adults with COVID-19: A structured summary of a study protocol for a randomized controlled trial
Authors: Eckhardt Christina M. , Cummings Matthew J. , Rajagopalan Kartik N. , Borden Sarah , Bitan Zachary C. , Wolf Allison , Kantor Alex , Briese Thomas , Meyer Benjamin J. , Jacobson Samuel D. , Scotto Dawn , Mishra Nischay , Philip Neena M. , Stotler Brie A. , Schwartz Joseph , Shaz Beth , Spitalnik Steven L. , Eisenberger Andrew , Hod Eldad A. , Justman Jessica , Cheung Ken , Lipkin W. Ian , O’Donnell Max R.
Published: June 2020

An amendment to this paper has been published and can be accessed via the original article.
Comparative therapeutic index, lethal time and safety margin of various toxicants and snake antivenoms using newly derived and old formulas
Authors: Saganuwan Saganuwan Alhaji
Published: June 2020

Objective

The assessment of clinical efficacy and toxicity is very important in pharmacology and toxicology. The effects of psychostimulants (e.g. amphetamine), psychotomimetics (e.g. Cannabis sativus) and snake antivenoms are sometimes unpredictable even at lower doses, leading to serious intoxication and fatal consequences. Hence, there is need to re-assess some formulas for calculation of therapeutic index, lethal time and safety margin with a view to identifying therapeutic agents with remarkable toxicity potentials.

Results

The therapeutic index formula $$\left[ {T_{1} = 3\left( {W_{a} \times 10^{ - 4} } \right)} \right]$$

T
1

=
3

W
a

×

10

-
4

was derived from T1 = LD50/ED50 and ED50 = $$\frac{{LD_{50} }}{3} x W_{a} \times 10^{ - 4}$$

L

D
50

3

x

W
a

×

10

-
4

. Findings have shown that, therapeutic index is a function of death reversal (s), safety factor (10−4) and weight of animal (Wa). However, the new safety margin formula $$\left[ {MS = \sqrt[3]{{\frac{{LT_{50} }}{{LD_{50} }}}} \times \frac{1}{{ED_{99} }}} \right]$$

M
S
=

L

T
50

L

D
50

3

×

1

E

D
99

derived from LT50 = $$\frac{{LD_{50} }}{{D_{1}^{p} }}$$

L

D
50

D

1

p

and MS = $$\frac{{LD_{1} }}{{ED_{99} }}$$

L

D
1

E

D
99

shows that safety margin is a function of cube root of ratio between LT50 and LD50 and ED100th. Concentration (k) of toxicant at the receptor $$\left[ {K = \sqrt[3]{{\frac{{LT_{50} }}{{LD_{50} }}}} \times \frac{1}{{T^{n} }}} \right]$$

K
=

L

T
50

L

D
50

3

×

1

T
n

derived from D1 × Tn = K and LD1 = $$\sqrt[3]{{\frac{{LT_{50} }}{{LD_{50} }}}}$$

L

T
50

L

D
50

3

shows that therapeutic index, lethal time and safety margin is a function of drug or toxicant concentration at the receptor, the drug-receptor interaction and dose of toxicant or drug administered at a particular time.
SOCRATES: an online tool leveraging a social contact data sharing initiative to assess mitigation strategies for COVID-19
Authors: Willem Lander , Van Hoang Thang , Funk Sebastian , Coletti Pietro , Beutels Philippe , Hens Niel
Published: June 2020

Objective

Establishing a social contact data sharing initiative and an interactive tool to assess mitigation strategies for COVID-19.

Results

We organized data sharing of published social contact surveys via online repositories and formatting guidelines. We analyzed this social contact data in terms of weighted social contact matrices, next generation matrices, relative incidence and R$$_{0}$$0. We incorporated location-specific physical distancing measures (e.g. school closure or at work) and capture their effect on transmission dynamics. All methods have been implemented in an online application based on R Shiny and applied to COVID-19 with age-specific susceptibility and infectiousness. Using our online tool with the available social contact data, we illustrate that physical distancing could have a considerable impact on reducing transmission for COVID-19. The effect itself depends on assumptions made about disease-specific characteristics and the choice of intervention(s).
Ochratoxigenic fungi and Ochratoxin A determination in dried grapes marketed in Tunisia
Authors: Chebil Samir , Rjiba-Bahri Wafa , Oueslati Souheib , Ben Ismail Hanen , Ben-Amar Anis , Natskoulis Pantelis
Published: June 2020

Purpose

With the present work, we aimed to assess the occurrence of ochratoxigenic fungi and Ochratoxin A (OTA) in dried grapes from Tunisia.

Methods

Dried grapes samples (n = 90) were investigated for the presence of ochratoxigenic fungi, which were further characterized at the species level through amplification of the internal transcribed spacer (ITS) region and polymerase chain reaction (PCR) product sequencing. Fungal isolates were tested for their ochratoxigenic potential by high-performance liquid chromatography with fluorescence detection (HPLC-FLD), as well as dried grapes samples after an immunoaffinity column (IAC) clean-up procedure.

Results

Black Aspergilli isolates were the dominant genre among the filamentous fungi found in dried grapes samples and were the only OTA-producing fungi encountered. Aspergillus niger aggregate were the most frequently found isolates reaching 70%, 80%, and 85% in dried grapes samples from regions of Kelibia, Sfax, and Rafraf, respectively, while covered 100% of the relevant mycobiota found in imported samples. Aspergillus carbonarius isolates were found only in Sfax’s and Kelibia’s samples, while uniseriate Aspergilli were found between 7 and 20% in dried grapes from Kelibia, Sfax, and the imported samples. The in vitro OTA production test showed that 88.9% of OTA-producing isolates belonged to A. carbonarius with OTA levels varying from 0.06 to 1.32 μg/g of Czapek Yeast Agar (CYA). The remaining OTA-producing fungi (11.1 %) belonged to A. niger aggregate group having a maximum OTA potential of 2.88 μg/g CYA, and no uniseriate Aspergilli isolate was able to produce OTA. All dried grapes samples were free of OTA presence.

Conclusion

According to the present study’s findings, no OTA contamination was recorded in the investigated samples from Tunisian market. Nevertheless, the presence of strong OTA producers A. carbonarius in samples originated from the two out of three studied Tunisian regions, as well the high incidences of Aspergillus niger aggregate group with an attested potential for OTA production in all samples, necessitates further research on Tunisian dried grapes. Additionally, a continuous analysis of staple food of the Mediterranean diet is imperative to insure the best quality for the consumers and prevent potential health problems.
The bacterial communities of Tuber aestivum: preliminary investigations in Molise region, Southern Italy
Authors: Monaco Pamela , Toumi Marwene , Sferra Gabriella , Tóth Erika , Naclerio Gino , Bucci Antonio
Published: June 2020

Purpose

Truffles are colonized by a complex microbial community of bacteria, yeasts, and filamentous fungi, whose role has not yet been fully understood. The main purpose of the research was to characterize the bacterial communities associated with Tuber aestivum Vittad. fruiting bodies collected from natural truffle grounds in the Molise region (Southern Italy). Despite it is one of the Italian richest areas of truffles, little is known about truffles in Molise.

Methods

Six ripe fruiting bodies of Tuber aestivum Vittad. and six soil samples were collected in July 2018 at Villa San Michele in the municipality of Vastogirardi, Molise region. Then, soil and truffle microbial communities were analyzed through 16S rRNA gene sequencing on the Illumina MiSeq platform and bioinformatics analyses.

Results

Consistently with previous studies, the main phyla retrieved in the investigated ascocarps were Proteobacteria and Actinobacteria, with the genus Bradyrhizobium particularly represented. Nevertheless, significant differences between soil and truffle microbiota and an unexpected heterogeneity across truffles were observed. It is likely that a specific recruitment of bacteria from soil to ascocarps occurs during the truffle formation and that local-scale factors play an important role in determining the structure of the investigated truffle microbial communities.

Conclusion

Although further analyses (based on a larger soil and truffle sample size and aimed at defining in more detail microbial diversity, soil physical and chemical properties, microclimatic conditions, and vegetation) are required to better understand which are these factors and how they could influence the composition of truffle bacterial communities, this study represents the starting point for a deepened characterization of this economically important product.
Sex differences in the first impressions made by girls and boys with autism
Authors: Cola Meredith L. , Plate Samantha , Yankowitz Lisa , Petrulla Victoria , Bateman Leila , Zampella Casey J. , de Marchena Ashley , Pandey Juhi , Schultz Robert T. , Parish-Morris Julia
Published: June 2020

Background

Individuals with autism spectrum disorder (ASD) are characterized by social communication challenges and repetitive behaviors that may be quickly detected by experts (Autism Res 10:653–62, 2017; American Psychiatric Association, Diagnostic and statistical manual of mental disorders, 2013). Recent research suggests that even naïve non-experts judge a variety of human dimensions using narrow windows of experience called “first impressions.” Growing recognition of sex differences in a variety of observable behaviors in ASD, combined with research showing that some autistic girls and women may “camouflage” outward symptoms, suggests it may be more difficult for naïve conversation partners to detect ASD symptoms in girls. Here, we explore the first impressions made by boys and girls with ASD and typically developing (TD) peers.

Methods

Ninety-three school-aged children with ASD or TD were matched on IQ; autistic girls and boys were additionally matched on autism symptom severity using the ADOS-2. Participants completed a 5-minute “get-to-know-you” conversation with a new young adult acquaintance. Immediately after the conversation, confederates rated participants on a variety of dimensions. Our primary analysis compared conversation ratings between groups (ASD boys, ASD girls, TD boys, TD girls).

Results

Autistic girls were rated more positively than autistic boys by novel conversation partners (better perceived social communication ability), despite comparable autism symptom severity as rated by expert clinicians (equivalent true social communication ability). Boys with ASD were rated more negatively than typical boys and typical girls by novel conversation partners as well as expert clinicians. There was no significant difference in the first impressions made by autistic girls compared to typical girls during conversations with a novel conversation partner, but autistic girls were rated lower than typical girls by expert clinicians.

Limitations

This study cannot speak to the ways in which first impressions may differ for younger children, adults, or individuals who are not verbally fluent; in addition, there were more autistic boys than girls in our sample, making it difficult to detect small effects.

Conclusions

First impressions made during naturalistic conversations with non-expert conversation partners could—in combination with clinical ratings and parent report—shed light on the nature and effects of behavioral differences between girls and boys on the autism spectrum.
Fast acquisition abdominal MRI study for the investigation of suspected acute appendicitis in paediatric patients
Authors: James Karl , Duffy Patrick , Kavanagh Richard G. , Carey Brian W. , Power Stephen , Ryan David , Joyce Stella , Feeley Aoife , Murphy Peter , Andrews Emmet , McEntee Mark F. , Moore Michael , Bogue Conor , Maher Michael M. , O’ Connor Owen J.
Published: June 2020

Objectives

To assess the diagnostic accuracy of fast acquisition MRI in suspected cases of paediatric appendicitis presenting to a tertiary referral hospital.

Materials and methods

A prospective study was undertaken between May and October 2017 of 52 children who presented with suspected appendicitis and were referred for an abdominal ultrasound. All patients included in this study received both an abdominal ultrasound and five-sequence MRI consisting of axial and coronal gradient echo T2 scans, fat-saturated SSFSE and a diffusion-weighted scan. Participants were randomised into groups of MRI with breath-holds or MRI with free breathing. A patient satisfaction survey was also carried out. Histopathology findings, where available, were used as a gold standard for the purposes of data analysis. Statistical analysis was performed, and p values < 0.05 were considered statistically significant.

Results

Ultrasound had a sensitivity and specificity of 25% and 92.9%, respectively. MRI with breath-hold had a sensitivity and specificity of 81.8% and 66.7%, respectively, whilst MRI with free breathing was superior with sensitivity and specificity of 92.3% and 84.2%, respectively. MRI with free breathing was also more time efficient (p < 0.0001). Group statistics were comparable (p < 0.05).

Conclusions

The use of fast acquisition MRI protocols, particularly free breathing sequences, for patients admitted with suspected appendicitis can result in faster diagnosis, treatment and discharge. It also has a statistically significant diagnostic advantage over ultrasound. Additionally, the higher specificity of MR can reduce the number of negative appendectomies performed in tertiary centres.
Imaging diagnosis of metastatic breast cancer
Authors: Pesapane Filippo , Downey Kate , Rotili Anna , Cassano Enrico , Koh Dow-Mu
Published: June 2020

Numerous imaging modalities may be used for the staging of women with advanced breast cancer. Although bone scintigraphy and multiplanar-CT are the most frequently used tests, others including PET, MRI and hybrid scans are also utilised, with no specific recommendations of which test should be preferentially used. We review the evidence behind the imaging modalities that characterise metastases in breast cancer and to update the evidence on comparative imaging accuracy.
Coinfections and their molecular consequences in the porcine respiratory tract
Authors: Saade Georges , Deblanc Céline , Bougon Juliette , Marois-Créhan Corinne , Fablet Christelle , Auray Gaël , Belloc Catherine , Leblanc-Maridor Mily , Gagnon Carl A. , Zhu Jianzhong , Gottschalk Marcelo , Summerfield Artur , Simon Gaëlle , Bertho Nicolas , Meurens François
Published: June 2020

Understudied, coinfections are more frequent in pig farms than single infections. In pigs, the term “Porcine Respiratory Disease Complex” (PRDC) is often used to describe coinfections involving viruses such as swine Influenza A Virus (swIAV), Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), and Porcine CircoVirus type 2 (PCV2) as well as bacteria likeActinobacillus pleuropneumoniae,Mycoplasma hyopneumoniaeandBordetella bronchiseptica. The clinical outcome of the various coinfection or superinfection situations is usually assessed in the studies while in most of cases there is no clear elucidation of the fine mechanisms shaping the complex interactions occurring between microorganisms. In this comprehensive review, we aimed at identifying the studies dealing with coinfections or superinfections in the pig respiratory tract and at presenting the interactions between pathogens and, when possible, the mechanisms controlling them. Coinfections and superinfections involving viruses and bacteria were considered while research articles including protozoan and fungi were excluded. We discuss the main limitations complicating the interpretation of coinfection/superinfection studies, and the high potential perspectives in this fascinating research field, which is expecting to gain more and more interest in the next years for the obvious benefit of animal health.
Mozambique’s response to cyclone Idai: how collaboration and surveillance with water, sanitation and hygiene (WASH) interventions were used to control a cholera epidemic
Authors: Lequechane Joaquim Domingos , Mahumane Arlete , Chale Falume , Nhabomba Crescêncio , Salomão Cristolde , Lameira Clemente , Chicumbe Sérgio , Semá Baltazar Cynthia
Published: June 2020

Cyclone Idai, which hit Mozambique in March 2019, was one of the worst climate-related natural disasters on record in the Southern Hemisphere causing massive destruction of housing and disruption to vital infrastructure including the electrical grid, communications and water supply. Almost two million people were affected with over 600 deaths, hundreds of thousands of people displaced accompanied by rapid spread of cholera. We describe emergency measures taken by the Government of Mozambique, in collaboration with multilateral partners, to establish a real-time disease surveillance system, implement interventions recommended by a Water, Sanitation and Hygiene (WASH) taskforce and rapidly scale up a massive community vaccination program to control a cholera epidemic.
Designing a tool to support patient and public involvement in research projects: the Involvement Matrix
Authors: Smits Dirk-Wouter , van Meeteren Karen , Klem Martijn , Alsem Mattijs , Ketelaar Marjolijn
Published: June 2020

Background

Interest in patient involvement in research is growing. Research should rather be ‘with’ or ‘by’ patients, and not only be ‘about’ or ‘for’ patients. Patients’ active involvement in research is not self-evident and special efforts have to be made. If we make efforts towards patient involvement, it could contribute to even more relevant projects with an even greater impact. In this paper we describe the process of development of a tool to support patient involvement in research projects.

Methods

The tool development was done in a co-creation of experience experts (patients and their parents/relatives) together with researchers. We used a participatory method in an iterative process comprising three consecutive stages. First, the purpose for the tool was explored, using focus groups. Second, the main ingredients and conceptualization for the tool were determined, using a narrative review. Third, the so-called Involvement Matrix was formalized and finalized using various expert panels.

Results

A conversation tool was developed, through which researchers and patients could discuss and explain their roles of involvement in a research project. This tool was formalized and visualized as a ‘matrix’. The so-called Involvement Matrix describes five roles (i.e., Listener, Co-thinker, Advisor, Partner, and Decision-maker) and three phases (i.e., Preparation, Execution, and Implementation) and includes a user’s guide.

Conclusion

The Involvement Matrix can be used prospectively to discuss about possible roles of patients in different phases of projects, and retrospectively to discuss whether roles were carried out satisfactorily. Sharing experiences with the Involvement Matrix and evaluating its impact are the next steps in supporting patient involvement in research.
Down syndrome and oral health: mothers’ perception on their children’s oral health and its impact
Authors: AlJameel AlBandary H. , Watt Richard G. , Tsakos Georgios , Daly Blánaid
Published: June 2020

Background

Individuals with Down syndrome exhibit particular oro-facial characteristics that may increase their risk of oral health problems. However, there is little research on the oral health of children and adults with Down syndrome and the way that oral health may affect Quality of Life (QoL). This study explored mothers’ perceptions of the oral health problems experienced by their children with Down syndrome and how these reported problems impacted the lives of the children and their families.

Methods

The study involved 20 in-depth, semi-structured interviews with mothers of children and adolescents aged 12–18 years with Down syndrome attending special care centres in Riyadh, Saudi Arabia.

Results

The predominant oral-health related problem reported by mothers was difficulty in speaking. Mothers also reported that tooth decay and toothache were problems that had undesirable effects on different aspects of their children’s QoL including: performing daily activities, emotional wellbeing, and social relationships. Poor oral health and functional problems had direct and indirect impacts on the family’s QoL as well.

Conclusion

Mothers perceived an array of QoL impacts from oral conditions, which affected their child with Down syndrome and the wider family.
Recovery from stroke: current concepts and future perspectives
Authors: Grefkes Christian , Fink Gereon R.
Published: June 2020

Stroke is a leading cause of acquired, permanent disability worldwide. Although the treatment of acute stroke has been improved considerably, the majority of patients to date are left disabled with a considerable impact on functional independence and quality of life. As the absolute number of stroke survivors is likely to further increase due to the demographic changes in our aging societies, new strategies are needed in order to improve neurorehabilitation. The most critical driver of functional recovery post-stroke is neural reorganization. For developing novel, neurobiologically informed strategies to promote recovery of function, an improved understanding of the mechanisms enabling plasticity and recovery is mandatory.

This review provides a comprehensive survey of recent developments in the field of stroke recovery using neuroimaging and non-invasive brain stimulation. We discuss current concepts of how the brain reorganizes its functional architecture to overcome stroke-induced deficits, and also present evidence for maladaptive effects interfering with recovery. We demonstrate that the combination of neuroimaging and neurostimulation techniques allows a better understanding of how brain plasticity can be modulated to promote the reorganization of neural networks. Finally, neurotechnology-based treatment strategies allowing patient-tailored interventions to achieve enhanced treatment responses are discussed. The review also highlights important limitations of current models, and finally closes with possible solutions and future directions.
Rapidly progressive COVID-19 viral pneumonia: a report of two patients with a focus on imaging findings
Authors: Zarrintan Armin , Javadrashid Reza , Tarzamni Mohammad Kazem , Zarrintan Anita , Falahatian Masih , Mirza-Aghazadeh-Attari Mohammad
Published: June 2020

Background

The novel coronavirus causes viral pneumonia characterized by lower respiratory tract symptoms and 19severe inflammatory response syndrome. Studies have suggested that the virus has a clinical course with the stepwise progression of clinical signs and symptoms and radiologic alterations.

Case presentation

In the present case report, we discuss two patients who presented with mild symptoms and CT imaging not suggestive of COVID-19, but subsequently had a rapid deterioration, with severe involvement happening in CT imaging. One of the patients survived the initial deterioration, but the other passed away.

Conclusion

We suggest that the clinical course of the virus may be rapidly progressive in some patients, and special attention should be paid to patients being treated for the virus outside of the hospital as an outpatient.
Potential of peel extracts of Punica granatum and Citrus aurantifolia on alloxan-induced diabetic rats
Authors: Ramya Sivasangari , Narayanan Vijayanand , Ponnerulan Boomibalagan , Saminathan Eswaran , Veeranan Uthirapandi
Published: June 2020

Background

Peel is one of the major by-products in fruit processing industry. Fruit products (non-edible parts) are also considered as waste products and often discarded in the environment. Fruit peels are now serving as one of the primary sources for isolation and extraction of secondary metabolites in pharmaceutical industry. The present investigation was carried out to screen the phytochemical constituents and HPTLC analysis of peel extracts of Punica granatum and Citrus aurantifolia and their antidiabetic potential in alloxan-induced diabetic rats.

Results

Among the different solvent extracts, methanol solvent extract was found to possess more amounts of secondary metabolites. In addition, HPTLC analysis of the plant samples revealed the presence of 13 peaks in both the plants by using gallic acid as marker. Different biochemical parameters such as blood glucose, cholesterol, protein, urea, creatinine, and triglycerides level were subjected for estimation by collecting the blood samples from the treated diabetic rats after 21 days. A sharp decline in blood glucose, cholesterol, triglycerides, creatinine, and urea level was noticed when methanolic extracts of Punica granatum and Citrus aurantifolia were given to experimental animals when compared with negative control. However, protein and weight of the animal were found to be enhanced when treated with methanolic extracts of both the plants.

Conclusion

It can be concluded that fruit peels of both the plants exhibited antidiabetic potential on alloxan-induced diabetic rats which can be attributed to wide range of active pool of secondary metabolites. Further, screening and isolation of secondary metabolites along with their mode of action is required for effective use of plant-based drugs as antihyperglycemic agent.

Graphical abstract
Services for self-harm: progress and promise?
Authors: Kapur Nav
Published: June 2020

This editorial considers whether the quality of care for people who present to clinical services in the UK following self-harm has improved or stagnated. Some real progress has been made in the areas of service provision and research, and self-harm has never had a higher priority in policy terms. However, major gaps remain. We need to enhance people's experience of services and improve access to high-quality assessment and aftercare.
Workflow Differences Affect Data Accuracy in Oncologic EHRs: A First Step Toward Detangling the Diagnosis Data Babel
Authors: Diaz-Garelli Franck , Strowd Roy , Lawson Virginia L. , Mayorga Maria E. , Wells Brian J. , Lycan Thomas W. , Topaloglu Umit
Published: June 2020

PURPOSE

Diagnosis (DX) information is key to clinical data reuse, yet accessible structured DX data often lack accuracy. Previous research hints at workflow differences in cancer DX entry, but their link to clinical data quality is unclear. We hypothesized that there is a statistically significant relationship between workflow-describing variables and DX data quality.

METHODS

We extracted DX data from encounter and order tables within our electronic health records (EHRs) for a cohort of patients with confirmed brain neoplasms. We built and optimized logistic regressions to predict the odds of fully accurate (ie, correct neoplasm type and anatomic site), inaccurate, and suboptimal (ie, vague) DX entry across clinical workflows. We selected our variables based on correlation strength of each outcome variable.

RESULTS

Both workflow and personnel variables were predictive of DX data quality. For example, a DX entered in departments other than oncology had up to 2.89 times higher odds of being accurate ( P < .0001) compared with an oncology department; an outpatient care location had up to 98% fewer odds of being inaccurate ( P < .0001), but had 458 times higher odds of being suboptimal ( P < .0001) compared with main campus, including the cancer center; and a DX recoded by a physician assistant had 85% fewer odds of being suboptimal ( P = .005) compared with those entered by physicians.

CONCLUSION

These results suggest that differences across clinical workflows and the clinical personnel producing EHR data affect clinical data quality. They also suggest that the need for specific structured DX data recording varies across clinical workflows and may be dependent on clinical information needs. Clinicians and researchers reusing oncologic data should consider such heterogeneity when conducting secondary analyses of EHR data.
EGFR activation attenuates the mechanical threshold for integrin tension and focal adhesion formation
Authors: Rao Tejeshwar C. , Ma Victor Pui-Yan , Blanchard Aaron , Urner Tara M. , Grandhi Shreya , Salaita Khalid , Mattheyses Alexa L.
Published: June 2020

Mechanical forces, growth factors and the extracellular matrix all play crucial roles in cell adhesion. To understand how epidermal growth factor receptor (EGFR) impacts the mechanics of adhesion, we employed tension gauge tether (TGT) probes displaying the integrin ligand cRGDfK and quantified integrin tension. EGF exposure significantly increased spread area, cell circularity, integrated integrin tension, mechanical rupture density, radial organization and size of focal adhesions in Cos-7 cells on TGT surfaces. These findings suggest that EGFR regulates integrin tension and the spatial organization of focal adhesions. Additionally, we found that the mechanical tension threshold for outside-in integrin activation is tunable by EGFR. Parallel genetic and pharmacologic strategies demonstrated that these phenotypes are driven by ligand-dependent EGFR signaling. Our results establish a novel mechanism whereby EGFR regulates integrin activation and cell adhesion, providing control over cellular responses to the environment.

This article has an associated First Person interview with the first author of the paper.
FAT10 localises in dendritic cell aggresome-like induced structures and contributes to their disassembly
Authors: Schregle Richard , Mueller Stefanie , Legler Daniel F. , Rossy Jérémie , Krueger Wolfgang A. , Groettrup Marcus
Published: June 2020

Dendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of polyubiquitylated proteins that form transiently during DC maturation. DALIS scatter randomly throughout the cytosol and serve as antigen storage sites synchronising DC maturation and antigen presentation. Maturation of DCs is accompanied by the induction of the ubiquitin-like modifier FAT10 (also known as UBD), which localises to aggresomes, structures that are similar to DALIS. FAT10 is conjugated to substrate proteins and serves as a signal for their rapid and irreversible degradation by the 26S proteasome similar to, yet independently of ubiquitin, thereby contributing to antigen presentation. Here, we have investigated whether FAT10 is involved in the formation and turnover of DALIS, and whether proteins accumulating in DALIS can be modified through conjunction to FAT10 (FAT10ylated). We found that FAT10 localises to DALIS in maturing DCs and that this localisation occurs independently of its conjugation to substrates. Additionally, we investigated the DALIS turnover in FAT10-deficient and -proficient DCs, and observed FAT10-mediated disassembly of DALIS. Thus, we report further evidence that FAT10 is involved in antigen processing, which may provide a functional rationale as to why FAT10 is selectively induced upon DC maturation.
TPC2-mediated Ca2+ signaling is required for axon extension in caudal primary motor neurons in zebrafish embryos
Authors: Guo Chenxi , Webb Sarah E. , Chan Ching Man , Miller Andrew L.
Published: June 2020

The role of two-pore channel type 2 (TPC2, encoded by tcpn2)-mediated Ca2+ release was recently characterized in zebrafish during establishment of the early spinal circuitry, one of the key events in the coordination of neuromuscular activity. Here, we extend our study to investigate the in vivo role of TPC2 in the regulation of caudal primary motor neuron (CaP) axon extension. We used a combination of TPC2 knockdown with a translation-blocking morpholino antisense oligonucleotide (MO), TPC2 knockout via the generation of a tpcn2dhkz1a mutant line of zebrafish using CRISPR/Cas9 gene-editing and pharmacological inhibition of TPC2 via incubation with bafilomycin A1 (an H+-ATPase inhibitor) or trans-ned-19 (an NAADP receptor antagonist), and showed that these treatments attenuated CaP Ca2+ signaling and inhibited axon extension. We also characterized the expression of an arc1-like transcript in CaPs grown in primary culture. MO-mediated knockdown of ARC1-like in vivo led to attenuation of the Ca2+ transients in the CaP growth cones and an inhibition of axon extension. Together, our new data suggest a link between ARC1-like, TPC2 and Ca2+ signaling during axon extension in zebrafish.
Association among helicobacter pylori infection, gastrin level and colorectal cancer in patients aged 50 years and over
Authors: Luan Chunyan , Liu Zhigang , Li Yongzhu , Dong Tao
Published: June 2020

Objectives: To study the correlations among helicobacter pylori infection, gastrin and colorectal cancer in patients aged over 50 years old.

Methods: In this study, the patients diagnosed with colorectal cancer treated in the department of digestion of our hospital together with the healthy subjects undergoing colonoscopy for health examination without pathologic findings from August 2016 to July 2019 were enrolled in colorectal cancer or control group. The blood sample was taken in fasting state, and anti-H. pylori IgG and anti-CagA antibodies as well as the level of serum gastrin were measured for all the participants. In addition, the information of each participant including age, gender, obesity, smoking history, alcohol consumption, diabetes mellitus was recorded and analyzed.

Results: Four hundred and twenty-eight patients were enrolled in the colorectal group and 207 healthy subjects were enrolled in the control group. There were not significant differences in the positive rate of Ig G and Cag A and family history between the two groups (p>0.05), but there were significant differences in gastrin level, obesity, smoking history, alcohol consumption and diabetes mellitus between the two groups (p<0.05). In addition, the multivariable analysis showed that obesity, smoking history, alcoholism and diabetes mellitus have the strongest influence on the formation of colorectal cancer, while the level of gastrin didn’t show the influence.

Conclusions: No significant correlations among H. pylori infection, the level of gastrin, and the occurrence of CRC in patients with a minimum age of 50 years, suggesting elder colorectal cancer patients may have a different carcinogenic mechanism from those younger patients.

doi: https://doi.org/10.12669/pjms.36.5.1993

How to cite this:Luan C, Liu Z, Li Y, Dong T. Association among helicobacter pylori infection, gastrin level and colorectal cancer in patients aged 50 years and over. Pak J Med Sci. 2020;36(5):899-903. doi: https://doi.org/10.12669/pjms.36.5.1993

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Correlation of serum levels of Vitamin D3 with serum parathormone in nursing mothers and infants 1-6 months’ age from South Punjab, Pakistan
Authors: Mustafa Ghulam , Khalid Muhammad , Ahmed Ijaz , Abu Talib Muhammad
Published: June 2020

Background and Objective: Parathormone (PTH) and serum Vitamin D3 (VD3) share a complex interplay where increased VD3 leads to a negative response on parathormone level. Our objective was to determine the correlation of parathormone (PTH) and Vitamin D3 (VD3) levels in nursing mothers and infants 1-6 months’ age from South Punjab, Pakistan.

Methods: This study is a secondary data analysis of previously conducted cross sectional study which was conducted at the Department of Pediatric Medicine, Nishtar Medical University, Multan, during August 2010 to June 2011. Study included 67 infants 1-6 months of age and 60 nursing mothers. A venous blood sample was drawn for estimation of VD3, calcium, phosphate, alkaline phosphatase, parathormone and albumin. Spearman correlation coefficient was calculated to determine the inverse correlation between PTH and VD3 levels.

Results: Mean age (in days) of the infants was 83±53.7 days whereas maternal mean age was 25.53 ± 4.12 years. Median VD3 level in infants was 20.90 ng/ml (IQR – 49.5). Median serum PTH levels were 20.90 pg/ml (IQR – 26.17). Median VD3 level in nursing mothers was 21.0 ng/ml (IQR 7.2– 43.8). Median maternal serum PTH levels were 20.89 pg/ml (IQR 2.9 – 232.4). Substantial negative relation between VD3 and parathormone in infants and mothers was not evident (r = - 0.027, p-value 0.83) and (r = 0.156, p-value 0.23) respectively. A significant positive association between infant and maternal VD3 was observed (rs –0.55, p-value < 0.001).

Conclusion: Our study affirms that the customary negative correlation between VD3 and parathormone levels does not exist.

doi: https://doi.org/10.12669/pjms.36.5.2150

How to cite this:Mustafa G, Khalid M, Ahmed I, Talib MA. Correlation of serum levels of Vitamin D3 with serum parathormone in nursing mothers and infants 1-6 months’ age from South Punjab, Pakistan. Pak J Med Sci. 2020;36(5):1015-1019. doi: https://doi.org/10.12669/pjms.36.5.2150

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Assessment of cell free mitochondrial DNA as a biomarker of disease severity in different viral infections
Authors: Ali Zain , Waseem Shahid , Anis Riffat Aysha , Anees Mariam
Published: June 2020

Objective: Cell Free mitochondrial DNA (CF mt-DNA) has emerged as a novel biomarker to investigate disease pathophysiology of different infections. The present study was designed to elucidate the association between CF mt-DNA, IL-6 and viral load in HIV, HBV and HCV infections and predict its role as a potential biomarker to assess the disease severity in viral infections.

Methods: Total 120 blood samples were collected from January 2018 to December 2018 of HIV, HBV and HCV patients and healthy controls (30 samples in each group). DNA and RNA were extracted from the serum to determine the levels of CF mt-DNA and viral load, respectively. IL-6 from the serum of infected individuals was quantified with ELISA.

Results: HCV patients showed the highest levels of CF mt-DNA, IL-6 and viral load, followed by HBV and HIV. Significant correlation was found between CF mt-DNA and IL-6 among the HBV patients (p=0.017). However, no significant correlation of CF mt-DNA was observed with IL-6 in HIV and HCV or with the viral load in any of the three infections.

Conclusion: Elevated CF mt-DNA indicates its role in severity of viral infections. Independence of CF mt-DNA expression from viral load and IL-6 in case of HIV and HCV suggests involvement of other inflammatory pathways regulating CF mt-DNA elevation.

doi: https://doi.org/10.12669/pjms.36.5.2476

How to cite this:Ali Z, Waseem S, Anis RA, Anees M. Assessment of cell free mitochondrial DNA as a biomarker of disease severity in different viral infections. Pak J Med Sci. 2020;36(5):860-866. doi: https://doi.org/10.12669/pjms.36.5.2476

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Technology of catering products
Authors: Dzyuba Grigoriy , Baranov Boris , Myasnikova Elena , Zhubreva Tat'yana , Sokolov Aleksandr
Published: June 2020

The tutorial discusses the processes occurring in the product under the influence of different treatments and factors that affect the quality of the finished product. Given the normative and technological documentation, as well as its use in the public catering enterprises. Includes laboratory work on the preparation and processing of semi-finished products, dishes, products and drinks.
Meets the requirements of Federal state educational standards of higher education of the last generation.
For students of educational institutions of higher education specializing in training 19.03.04 "production Technology and organization of public catering".
A Classical Logic of Existence and Essence
Authors: Galvan Sergio , Giordani Alessandro
Published: June 2020

The purpose of this paper is to provide a new system of logic for existence and essence, in which the traditional distinctions between essential and accidental properties, abstract and concrete objects, and actually existent and possibly existent objects are described and related in a suitable way. In order to accomplish this task, a primitive relation of essential identity between different objects is introduced and connected to a first order existence property and a first order abstractness property. The basic idea is that possibly existent objects are completely determinate and that essentially identical objects are just different individuations of the same individual essence. Accordingly, essential properties are defined as properties that are invariant with respect to this kind of identity, while abstract objects are determined by being characterized by essential properties only. Once such ideas are implemented, a number of classical intuitions about objects, their essence, and their way of existence can be consistently interpreted.
New Exact Algorithm for the Vehicle Routing Problem with Stochastic Demands
Authors: Florio Alexandre M. , Hartl Richard F. , Minner Stefan
Published: June 2020

This paper considers the vehicle routing problem with stochastic demands under optimal restocking. We develop an exact algorithm that is effective for solving instances with many vehicles and few customers per route. In our experiments, we show that in these instances, solving the stochastic problem is most relevant (i.e., the potential gains over the deterministic equivalent solution are highest). The proposed branch-price-and-cut algorithm relies on an efficient labeling procedure, exact and heuristic dominance rules, and completion bounds to price profitable columns. Instances with up to 76 nodes could be solved in less than five hours, and instances with up to 148 nodes could be solved in long runs of the algorithm. The experiments also allowed new findings on the problem. The solution to the stochastic problem is up to 10% less costly than the deterministic equivalent solution. Opening new routes reduces restocking costs and in many cases results in solutions with less transportation costs. When the number of routes is not fixed, the optimal solutions under detour-to-depot and optimal restocking are nearly equivalent. However, when the number of routes is limited and the expected demand along a route is allowed to exceed the vehicle capacity, optimal restocking may be significantly more cost-effective than the detour-to-depot policy.
Tracking sub-nanometer thermal structural changes with speckle interferometry
Authors: Saif Babak , Greenfield Perry , Bluth Marcel , Feinberg Lee , Wyant J. C. , Keski-Kuha Ritva
Published: June 2020

Based on our results of the James Webb Space Telescope (JWST) center-of-curvature tests where we were able to measure dynamic amplitudes of Zernike terms to the order of a few picometers, we have applied the same approach to determine if it is possible to measure the accuracy of higher-order Zernike terms as a function of time rather than frequency, i.e., static measurements in place of measuring the amplitude of frequency components. We have applied this approach to data taken for the JWST backplane structure test article (BSTA) in 2006 and find that we can measure effects at the sub-nanometer level, as small as 50 pm for Zernike terms over 30. We conclude that these results show it will be possible to use these techniques to ensure that the optics and support structure for large space telescopes can meet the necessary stability requirements for detecting spectral signatures of life on Earth-like extra-solar planets.
Evaluation of transdermal drug delivery using terahertz pulsed imaging
Authors: Wang Jiarui , Lindley-Hatcher Hannah , Liu Kai , Pickwell-MacPherson Emma
Published: June 2020

Transdermal drug delivery (TDD) is widely used for painless dosing due to its minimally invasive nature compared to hypodermic needle injection and its avoidance of the gastrointestinal tract. However, the stratum corneum obstructs the permeation of drugs into skin. Microneedle and nanoneedle patches are ways to enhance this permeation. In this work, terahertz (THz) imaging is utilized to compare the efficacy of different TDD methods including topical application and via a needle patch. Our work shows the feasibility and potential of using THz imaging to quantify and evaluate different transdermal application methods.
Sensorless adaptive-optics optical coherence tomographic angiography
Authors: Camino Acner , Zang Pengxiao , Athwal Arman , Ni Shuibin , Jia Yali , Huang David , Jian Yifan
Published: June 2020

Optical coherence tomographic angiography (OCTA) can image the retinal blood flow but visualization of the capillary caliber is limited by the low lateral resolution. Adaptive optics (AO) can be used to compensate ocular aberrations when using high numerical aperture (NA), and thus improve image resolution. However, previously reported AO-OCTA instruments were large and complex, and have a small sub-millimeter field of view (FOV) that hinders the extraction of biomarkers with clinical relevance. In this manuscript, we developed a sensorless AO-OCTA prototype with an intermediate numerical aperture to produce depth-resolved angiograms with high resolution and signal-to-noise ratio over a 2 × 2 mm FOV, with a focal spot diameter of 6 µm, which is about 3 times finer than typical commercial OCT systems. We believe these parameters may represent a better tradeoff between resolution and FOV compared to large-NA AO systems, since the spot size matches better that of capillaries. The prototype corrects defocus, astigmatism, and coma using a figure of merit based on the mean reflectance projection of a slab defined with real-time segmentation of retinal layers. AO correction with the ability to optimize focusing in arbitrary retinal depths – particularly the plexuses in the inner retina – could be achieved in 1.35 seconds. The AO-OCTA images showed greater flow signal, signal-to-noise ratio, and finer capillary caliber compared to commercial OCTA. Projection artifacts were also reduced in the intermediate and deep capillary plexuses. The instrument reported here improves OCTA image quality without excessive sacrifice in FOV and device complexity, and thus may have potential for clinical translation.
Absolute laser ranging by time-of-flight measurement of ultrashort light pulses [Invited]
Authors: Kim Wooram , Jang Jaeyoung , Han Seongheum , Kim Seungman , Oh Jeong Seok , Kim Byung Soo , Kim Young-Jin , Kim Seung-Woo
Published: June 2020

Ultrashort pulse lasers are emerging as an advanced tool of distance
measurement, with their unique temporal and spectral characteristics
being extended to diverse principles of absolute ranging and
instrumentation. Here, a systematic methodology is presented for
absolute ranging by means of the time-of-flight measurement of
ultrashort light pulses using dual-comb asynchronous optical sampling.
Based on an elaborate uncertainty analysis, influencing system
parameters such as the pulse duration, repetition rate, and averaging
time are optimized to achieve a sub-µm measurement accuracy. The
absolute ranging system developed in this study demonstrates a
combined standard uncertainty of 0.986 µm for a 0.5 ms averaging over
a distance range of 3.0 m, with a further reduction to 0.056 µm when
the averaging time is increased to 0.5 s. The outstanding performance
leads to unprecedented multitarget applications: machine feed control
with thermal error compensation in real time as well as the
nondestructive inspection of multilens assembly in a production
line.