bluuebunny/crossref_metadata_2025 huggingface dataset:
Noncanonical interactions of G proteins and β‐arrestins: from competitors to companions
Authors: Smith Jeffrey S. , Pack Thomas F.
Published: February 2021

G protein‐coupled receptors (GPCRs) canonically couple to specific Gα protein subtypes and β‐arrestin adaptor proteins to initiate cellular signaling events. G protein‐mediated signaling and β‐arrestin‐mediated signaling have broadly been considered separable. However, noncanonical interactions between G proteins and GPCRs are now appreciated that do not result in nucleotide exchange and classical G protein signaling. New findings also demonstrate direct interactions between G proteins and β‐arrestins that are required for certain signaling and physiological events. Further adding to the intrigue of these newly appreciated G protein:β‐arrestin complexes, only the Gαi subtype family members, and not Gαs, Gαq/11, or Gα12/13 subtypes, appear to form direct interactions with β‐arrestin. Here, we review the recent discovery and initial characterization of G protein:β‐arrestin complexes and describe how these complexes provide mechanistic insight into seemingly disparate observations. G protein:β‐arrestin complexes build upon other observations of noncanonical G protein and β‐arrestin signaling events to add an additional dimension to our understanding of GPCR signaling.
Clinicopathological analysis of low‐grade papillary Schneiderian carcinoma: report of five new cases and review of the literature
Authors: Zhai Changwen , Wang Huan , Li Shimin , Wang Dehui
Published: February 2021

Aims

Low‐grade papillary Schneiderian carcinoma (LGPSC) is a rare and newly described entity of the sinonasal tract. The aim of this study was to evaluate the clinicopathological and molecular characteristics in order to identify typical features for differential diagnosis.

Methods and results

Of the 3000 cases of sinonasal tumour studied during a period of 6 years, five cases were reviewed and diagnosed as LGPSC. All five patients were female (mean age, 47.8 years; range, 18–64 years) and had undergone multiple surgeries (3–10 surgeries). Both the sinonasal tract and the middle ear were involved in four patients. Nodal metastasis occurred in two patients, and one patient developed a distant metastasis to the left lung. Histologically, tumours had branched and crowded papillae with pushing boundaries. Tumour epithelia were multilayered and arranged in an orderly pattern without cilia. No malignant cytological features were observed in any of the cases. Immunohistochemical findings revealed a scattered distribution of Ki67‐positive cells and positive staining for epithelial membrane antigen, mainly in the outermost‐layer cells. Human papillomavirus (HPV) DNA was found in two patients and genotyped as HPV type 16. Sanger sequencing did not reveal any epidermal growth factor receptor or Kirsten rat sarcoma viral oncogene homologue gene mutation in the five cases.

Conclusions

We report on five new cases of LGPSC, and confirm LGPSC as a new sinonasal carcinoma that behaves aggressively with metastatic potential. The combination of clinical behaviour and typical histological features can distinguish LGPSC from sinonasal papilloma and other carcinomas.
Influence of botulinum toxin type A esthetic injections on facial expressions
Authors: Foissac Rémi , Benatar Marc J.
Published: February 2021

Background

Botulinum toxin type A (BoNT‐A) injection remains the leading medical cosmetic procedure worldwide, with a high rate of patient satisfaction. However, it still suffers from patients’ fear of being unable to transmit their emotions and of looking frozen from unnatural results.

Aim

This study aimed to determine whether BoNT‐A can decrease the intensity of emotions in facial expressions.

Patients/Methods

In this single‐center prospective study, 42 patient investigators assessed four patients’ facial expressions for six emotions and neutral faces, before and after injection of 36 IU or 48 IU of onabotulinumtoxinA, using photographs. Photographs were presented on a tablet to the investigators.

Results

There were no statistical differences between the before and after photographs for the intensity of emotions for all expressions (P > .05) except for the expression of surprise in the group of patients that received 48 IU of the injection (protocol with injection of the frontalis muscle). All patient investigators answered negatively to the question “Do you think that this patient has a ‘frozen face’?”.

Conclusion

This study shows that esthetic injection of BoNT‐A in the upper face has no negative effects on facial expressions and does not lead to the feared “frozen face” when it is injected with respect for best practice guidelines. This study can be used as an example for patients who have some reticences against BoNT‐A injection.
Simple Duplication Technique of Complete Denture Using an Intraoral Scanner
Authors: Oyamada Yutaro , Yonezawa Yu , Kondo Hisatomo
Published: February 2021

Various techniques have been applied to the fabrication of duplicate dentures. In this new method, after scanning the cameo and intaglio surfaces of the complete denture using an intraoral scanner, the two images were superimposed on the interocclusal image. The linear gap between cameo and intaglio surfaces was filled using free downloadable CAD software. The superimposed image was subsequently used as data for fabricating the duplicate complete denture with a 3D printer. Using the intraoral scanner, duplication of complete dentures could be performed without needing any complicated processes, laboratory scanners, or advanced CAD software.
Bariatric surgery and the risk of alcohol‐related cirrhosis and alcohol misuse
Authors: Mellinger Jessica L. , Shedden Kerby , Winder G. Scott , Fernandez Anne C. , Lee Brian P. , Waljee Jennifer , Fontana Robert , Volk Michael L. , Blow Frederic C. , Lok Anna S. F.
Published: February 2021

Background & Aims

Bariatric surgery is common, but alcohol misuse has been reported following these procedures. We aimed to determine if bariatric surgery is associated with increased risk of alcohol‐related cirrhosis (AC) and alcohol misuse.

Methods

Retrospective observational analysis of obese adults with employer‐sponsored insurance administrative claims from 2008 to 2016. Subjects with diagnosis codes for bariatric surgery were included. Primary outcome was risk of AC. Secondary outcome was risk of alcohol misuse. Bariatric surgery was divided into before 2008 and after 2008 to account for patients who had a procedure during the study period. Cox proportional hazard regression models using age as the time variable were used with interaction analyses for bariatric surgery and gender.

Results

A total of 194 130 had surgery from 2008 to 2016 while 209 090 patients had bariatric surgery prior to 2008. Age was 44.1 years, 61% women and enrolment was 3.7 years. A total of 4774 (0.07%) had AC. Overall risk of AC was lower for those who received sleeve gastrectomy and laparoscopic banding during the study period (HR 0.4, P <.001; HR 0.43, P =.02) and alcohol misuse increased for Roux‐en‐Y and sleeve gastrectomy recipients (HR 1.86 and 1.35, P <.001, respectively). In those who had surgery before 2008, women had increased risk of AC and alcohol misuse compared to women without bariatric surgery (HR 2.1 [95% CI: 1.79‐2.41] for AC; HR 1.98 [95% CI 1.93‐2.04]).

Conclusions

Bariatric surgery is associated with a short‐term decreased risk of AC but potential long‐term increased risk of AC in women. Post‐operative alcohol surveillance is necessary to reduce this risk.
The polymict carbonaceous breccia Aguas Zarcas: A potential analog to samples being returned by the OSIRIS‐REx and Hayabusa2 missions
Authors: Kerraouch Imene , Bischoff Addi , Zolensky Michael E. , Pack Andreas , Patzek Markus , Hanna Romy D. , Fries Marc D. , Harries Dennis , Kebukawa Yoko , Le Loan , Ito Motoo , Rahman Zia
Published: February 2021

On April 23, 2019, a meteorite fall occurred in Aguas Zarcas, Costa Rica. According to the Meteoritical Bulletin, Aguas Zarcas is a brecciated CM2 chondrite dominated by two lithologies. Our X‐ray computed tomography (XCT) results show many different lithologies. In this paper, we describe the petrographic and mineralogical investigation of five different lithologies of the Aguas Zarcas meteorite. The bulk oxygen isotope compositions of some lithologies were also measured. The Aguas Zarcas meteorite is a breccia at all scales. From two small fragments, we have noted five main lithologies, including (1) Met‐1: a metal‐rich lithology; (2) Met‐2: a second metal‐rich lithology which is distinct from Met‐1; (3) a brecciated CM lithology with clasts of different petrologic subtypes; (4) a C1/2 lithology; and (5) a C1 lithology. The Met‐1 lithology is a new and unique carbonaceous chondrite which bears similarities to CR and CM chondrite groups, but is distinct from both based on oxygen isotope data. Met‐2 also represents a new type of carbonaceous chondrite, but it is more similar to the CM chondrite group, albeit with a very high abundance of metal. We have noted some similarities between the Met‐1 and Met‐2 lithologies and will explore possible genetic relationships. We have also identified a brecciated CM lithology with two primary components: a chondrule‐poor lithology and a chondrule‐rich lithology showing different petrologic subtypes. The other two lithologies, C1 and C1/2, are very altered and possibly related to the CM chondrite group. In this article, we describe all the lithologies in detail and attempt a classification of each in order to understand the origin and the history of formation of the Aguas Zarcas parent body.
An act of performance: Exploring residents’ decision‐making processes to seek help
Authors: Jansen Iris , Stalmeijer Renée E. , Silkens Milou E. W. M. , Lombarts Kiki M. J. M. H.
Published: February 2021

Context

Residents are expected to ask for help when feeling insufficiently confident or competent to act in patients’ best interests. While previous studies focused on the perspective of supervisor‐resident relationships in residents’ help‐seeking decisions, attention for how the workplace environment and, more specifically, other health care team members influence these decisions is limited. Using a sociocultural lens, this study aimed to explore how residents’ decision‐making processes to seek help are shaped by their workplace environment.

Methods

Through a constructivist grounded theory methodology, we purposively and theoretically sampled 18 residents: 9 juniors (postgraduate year 1/2) and 9 seniors (postgraduate year 5/6) at Amsterdam University Medical Centers. Using semi‐structured interviews, participating residents’ decision‐making processes to seek help during patient care delivery were explored. Data collection and analysis were iterative; themes were identified using constant comparative analysis.

Results

Residents described their help‐seeking decision‐making processes as an ‘act of performance’: they considered how asking for help could potentially impact their assessments. They described this act of performance as the product of an internal ‘balancing act’ with at its core the non‐negotiable priority for providing safe and high‐quality patient care. With this in mind, residents weighed up demonstrating the ability to work independently, maintaining credibility and becoming an accepted member of the health care team when deciding to seek help. This ‘balancing act’ was influenced by sociocultural characteristics of the learning environment, residents’ relationships with supervisors and the perceived approachability of other health care team members.

Conclusions

This study suggests that sociocultural forces influence residents to experience help‐seeking as an act of performance. Especially, a safe learning environment resulting from constructive relationships with supervisors and the approachability of other health care team members lowered the barriers to seek help. Supervisors could address these barriers by having regular conversations with residents about when to seek help.
Serotonin contributes to the in vitro production of a biomimetic enamel‐like material from reprogrammed oral epithelial keratinocytes
Authors: Bazina Fayrouz , Brouxhon Sabine M. , Graham Uschi M. , Kyrkanides Stephanos
Published: February 2021

Objectives

To evaluate the role of serotonin in the development of a biomimetic enamel‐like material in vitro.

Setting and Sample population

Immortalized murine oral keratinocytes raised from adult mouse mucosa were cultured in vitro. In addition, specimens incorporating molar tooth buds harvested from mice were included in our studies.

Materials and Methods

We used cell‐based scaffold‐free tissue engineering to assemble three‐dimensional (3D) organoids into complex tissue constructs that closely emulate the complexity of adult enamel. We also analysed mouse molar specimens using immunohistochemistry for serotonin expression as well as its cognate receptor.

Results

TGF‐β1–reprogrammed murine oral keratinocytes formed organoids that laid down an amelogenin‐rich protein matrix when grown as three‐dimensional (3D) cultures in the presence of serotonin. Following mineralization, the newly formed crystals were densified under pressure and vacuum to produce a biomimetic enamel‐like material that demonstrated parallel alignment of hydroxyapatite crystals with some interspaced residual organoid matter into enamel prism‐like structures conferring size, mechanical properties comparable to tooth enamel, including light translucency. Serotonin expression was localized by immunohistochemistry proximal to the enamel organ of developing molar buds. Moreover, serotonin HTRb2 receptor expression was localized on ameloblasts within the enamel organ proximal to the area where serotonin was immunolocalized.

Conclusions

Our results demonstrate that serotonin is inductive in the development of a biomimetic enamel‐like material from reprogrammed oral epithelial keratinocytes in vitro. The facileness of harvesting adult somatic cells together with the versatility of our approach offers exciting opportunities to address regenerative challenges linked to lost enamel.
Dental caries and depression in pregnant women: The role of oral health self‐perception as mediator
Authors: Cademartori Mariana G. , Demarco Flavio F. , Freitas da Silveira Mariangela , Barros Fernando C. , Corrêa Marcos B.
Published: February 2021

Objective

This study investigated the role of oral health self‐perception as mediator of association between dental caries and depression among pregnant women from the 2015 Pelotas Birth Cohort Study, Brazil.

Materials and Methods

Overall, 2,496 pregnant women participated of this oral health sub‐study. Data related to demographic and socioeconomic conditions, lifetime and current depression, and oral health self‐perception were collected. Participants were also assessed for dental caries (DMF‐T index). Depression was assessed using the Edinburgh Postnatal Depression Scale. For analysis, six outcomes related to dental caries experience were considered. Causal mediation analysis was performed using parametric regression models.

Results

When it was assumed that all subjects had poor perception about oral health, it was observed that the presence of moderate/severe depressive signals and symptoms was higher in subjects with dental caries experience (OR 1.13; CI 95% 1.06–1.20), with severity of untreated dental caries (OR 2.08; CI 95% 1.16–3.78), untreated dental caries (OR 1.18; 95% CI 1.07–1.29), tooth loss (OR 1.08; 95% CI 1.02–1.14), and filled tooth (OR 1.07; 95% CI 1.02–1.16).

Conclusions

Our findings show the effect of dental caries on depression is mediated by self‐perception about oral health in pregnant women.
Prevalence of Problematic Use of Opioids in Patients with Chronic Noncancer Pain: A Systematic Review with Meta‐analysis
Authors: Jantarada Cláudia , Silva Catarina , Guimarães‐Pereira Luís
Published: February 2021

Background and Objective

Opioid prescription for chronic noncancer pain is associated with problematic use. We aimed to review and summarize the evidence on the prevalence of problematic use of opioids in adults with chronic noncancer pain and investigate whether the prevalence rates were changing over time.

Databases and Data Treatment

A systematic review of the literature was undertaken following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. We systematically searched the literature in the electronic databases MEDLINE, SCOPUS, and Web of Science and studies with adult participants with chronic noncancer pain using opioids with indication of one or more of the following terms about problematic opioid use: abuse, misuse, addiction, dependence, problematic use, and aberrant behavior/use were eligible for data extraction. Meta‐analysis was performed to estimate the pooled prevalence rates using a random‐effects model, and subanalysis was conducted.

Results

Our search identified a total of 784 potentially relevant studies. After a thorough evaluation, 19 papers, mostly from the United States, were included in our qualitative and quantitative synthesis. The majority of the data came from speciality pain clinics. The estimated prevalence of problematic use of opioids in adults with chronic noncancer pain was 36.3% (95% confidence interval: 27.4 to 45.2%; I2 = 99.64%). Problematic opioid use was mostly identified using the questionnaire method. Thirteen studies (68%) presented a low risk of bias.

Conclusions

Our study presents an alarming estimate regarding the prevalence of problematic use of opioids among patients with noncancer pain. These results deserve special attention from health care professionals and health authorities.
A field study using different technologies to detect calving at a large‐scale hungarian dairy farm
Authors: Horváth András , Lénárt Lea , Csepreghy Anna , Madar Márta , Pálffy Mátyás , Szenci Ottó
Published: February 2021

The objective of this study was to investigate three different calving detection systems in order to assess and compare their efficiency. The study was conducted at a large‐scale dairy farm involving 54 Holstein‐Friesian dairy cows and heifers. Animals were fitted with multiple devices: a rumination measuring device (Ruminact® (RA)), an intravaginal thermometer (Vel’Phone® (VP)) and a tail movement sensor (Moocall® (MC)) 5 to 7 days before expected calving and were removed after parturition. RA detects rumination time (RT) and calculates it in 2‐hr intervals. VP detects a decrease in vaginal temperature that might indicate calving within 48 hr and the drop in temperature resulting from the expulsion of the device at calving (EXP message). MC detected increased tail movements and if they persisted for one hour, 1HA message was sent. If they continued during the subsequent hour, then 2HA message was sent. Messages sent by MC within 4 hr before calving (C4) were selected retrospectively as true positives for the prediction of calving, using the significant changes in RT as a baseline. All other messages were categorized as false positive. The mean value of RT decreased in a non‐significant manner between interval −22 and −4 before calving. Significant decrease of RT was detectable between the two intervals of −4 and −2 before calving (24.7 ± 18.6 min/2 hr and 14.0 ± 13.0 min/2 hr, respectively). There was no significant difference between RT of primiparous and multiparous animals. EXP messages were accurate (positive predictive value 100%) indicators of the onset of calving. We received on average 12.7 ± 15.2 messages/animal (11.0 ± 10.1 and 16.6 ± 22.2 for cows and heifers, respectively). Positive predictive value was 12.6%. The number of false‐positive messages was significantly higher in heifers. All three automatic systems could be used in a large‐scale farm environment.
“We have to create our own community”: Addressing HIV/AIDS among Men who have Sex with Men (MSM) in the Neuropolis
Authors: Hassan Neil R. , Tucker Andrew
Published: February 2021

The inclusion of Men who have Sex with Men (MSM) in global health policies has resulted in significant resource prioritisations in order to treat and prevent the Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS). MSM policy inclusions and health prioritisations, however, are primarily motivated by an epidemiological understanding of male same‐sex sexual behaviours, based on biological risks associated with HIV infection. Owing to South Africa's high HIV rates and MSM policy prioritisations, we aimed to examine experiences of engagement in urban MSM‐targeted HIV interventions. Qualitative interviews were conducted with participants (n = 20) who previously engaged in MSM‐HIV interventions, across a variety of historically marginalised “township” spaces in Cape Town, South Africa. Interviews were audio‐recorded with the consent of all participants, transcribed verbatim, and verified, and anonymised using alpha‐numeric codes. Data were analysed for core themes and in this paper we describe interactions between biological and social risks that shape city life for MSM in diverse township spaces. When positioned against the background of the Neuropolis, a recent sociological intervention by Des Fitzgerald, Nikolas Rose and Ilina Singh, our results portray urban life among MSM as a form of biological citizenship: (1) constructed by experiences that are constitutive of biosocial stressors, based on (2) health‐seeking attitudes and behaviours, and (3) reinforced through socio‐spatial engagements in peer‐led and community‐based HIV interventions. We conclude by offering critical insight into recent calls for the development of comprehensive and localised peer‐led health programmes as a current void in the geographies of health and sexualities in the global south.
Simulation of Hyperelasticity by Shape Estimation
Authors: Matte Christopher-Denny , Kwok Tsz-Ho
Published: February 2021

The simulation of complex geometries and non-linear deformation has been a challenge for standard simulation methods. There has traditionally been a trade-off between performance and accuracy. With the popularity of additive manufacturing and the new design space it enables, the challenges are even more prevalent. Additionally, multiple additive manufacturing techniques now allow hyperelastic materials as raw material for fabrication and multi-material capabilities. This allows designers more freedom but also introduces new challenges for control and simulation of the printed parts. In this paper, a novel approach to implementing non-linear material capabilities is devised with negligible additional computations for geometry-based methods. Material curves are fitted with a polynomial expression, which can determine the tangent modulus, or stiffness, of a material based on strain energy. The moduli of all elements are compared to determine relative shape factors used to establish an element’s blended shape. This process is done dynamically to update a material’s stiffness in real-time, for any number of materials, regardless of linear or non-linear material curves.
Cutting down the hematopoietic tree: E-cadherin reveals a landscape of differentiating basophils and mast cells
Authors: Dahlin Joakim S.
Published: February 2021

GATA-2–mediated E-cadherin expression marks early progenitors primed to the basophil and mast cell lineages in mouse hematopoiesis (see the related Research Article by

Wanet
et al
.

).
The Benefits of Exporting: Engineered Extracellular Vesicles as Promising Vaccine Candidates against Enteric Fever
Authors: Rodrigues Marcio L.
Published: February 2021

The immunological potential of extracellular vesicles produced by Gram-negative bacteria, the so-called outer-membrane vesicles (OMVs), can be improved by genetic engineering, resulting in vesicles containing multiple immunogens. The potential of this approach for the development of a vaccine candidate for enteric fever was recently demonstrated by Gasperini and colleagues.
Identification of Potential Regulatory Domains within the MreC and MreD Components of the Cell Elongation Machinery
Authors: Rohs Patricia D. A. , Qiu Jeanna M. , Torres Grasiela , Smith Mandy D. , Fivenson Elayne M. , Bernhardt Thomas G.
Published: February 2021

Cell shape in bacteria is largely determined by the cell wall structure that surrounds them. The multiprotein machine called the Rod system (elongasome) has long been implicated in rod shape determination in bacilli.
Paroxysmal kinesigenic dyskinesia: a diagnostic challenge
Authors: Dayasiri Kavinda , Weerapperuma Nilushika , Wright Juliana , Anand Geetha
Published: February 2021

A 10-year-old girl presented with a month long history of episodic limb movements. She had a normal neurological examination and after thorough investigation, she was thought to have possible tics. Anxiety was reported as being a trigger. Unusually, these ‘tics’ were not directly witnessed during hospital visits. Eighteen months after the initial presentation, the clinician observed dystonic posturing after the child stood up from having been seated during a consultation. Paroxysmal kinesigenic dyskinesia (PKD) was then suspected and confirmed on genetic testing. She was successfully treated with carbamazepine. In hindsight, it became apparent that her anxiety was related to a fear of uncontrolled movements, rather than it being a trigger. The abnormal involuntary movements in PKD are precipitated by sudden voluntary movement. Lack of recognition of this typical feature, normal examination and/or features such as coexisting anxiety can lead to misdiagnosis or delayed diagnosis of this easily treatable condition.
Effect of Instrumental Activities of Daily Living habituation due to routinising therapy in patients with frontotemporal dementia
Authors: Nakanishi Kosuke , Yamaga Takayoshi
Published: February 2021

We examined whether Instrumental Activities of Daily Living (IADL) improves with routinising therapy for a patient with frontotemporal dementia (FTD) living in a group home. The patient exhibited symptoms of agitation, apathy, disinhibition, irritability and stereotyped behaviour. The care staff experienced long-term care burden and the patient was spending time idly. An occupational therapist, in collaboration with care staff, evaluated the patient and routinised the household chores included in IADL. Consequently, a routine of household chores was established, reducing behavioural and psychological symptoms of dementia and long-term care burden, and the quality of life (QOL) of the patient improved. The results suggested that routinising IADL of the patient with FTD reduced long-term care burden and improved QOL of the patient.
Case of laparoscopic-assisted anorectoplasty performed with temporary umbilical loop colostomy for high anorectal malformation (rectovesical fistula): a three-stage minimally invasive surgery
Authors: Isa Hideki , Miyagi Hisayuki , Ishii Daisuke , Hirasawa Masatoshi
Published: February 2021

This is the first report of three-stage laparoscopic-assisted anorectoplasty (LAARP) with temporary umbilical loop colostomy aiming for minimally invasive surgery in a boy with high anorectal malformation. The procedure was performed safely and resulted in small inconspicuous wounds. LAARP with temporary umbilical loop colostomy was a sufficiently useful therapeutic approach to high anorectal malformation.
Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects
Authors: Adam M Gordian , Beyer Georg , Christiansen Nicole , Kamlage Beate , Pilarsky Christian , Distler Marius , Fahlbusch Tim , Chromik Ansgar , Klein Fritz , Bahra Marcus , Uhl Waldemar , Grützmann Robert , Mahajan Ujjwal M , Weiss Frank U , Mayerle Julia , Lerch Markus M
Published: February 2021

Objective

Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management.

Design

We conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines. A signature to distinguish CP from controls (n=160) was identified using gas chromatography-mass spectrometry and liquid chromatography‐tandem mass spectrometry on ethylenediaminetetraacetic acid (EDTA)-plasma and validated in independent cohorts.

Results

A Naive Bayes algorithm identified eight metabolites of six ontology classes. After algorithm training and computation of optimal cut-offs, classification according to the metabolic signature detected CP with an area under the curve (AUC) of 0.85 ((95% CI 0.79 to 0.91). External validation in two independent cohorts (total n=502) resulted in similar accuracy for detection of CP compared with non-pancreatic controls in EDTA-plasma (AUC 0.85 (95% CI 0.81 to 0.89)) and serum (AUC 0.87 (95% CI 0.81 to 0.95)).

Conclusions

This is the first study that identifies and independently validates a metabolomic signature in plasma and serum for the diagnosis of CP in large, prospective cohorts. The results could provide the basis for the development of the first routine laboratory test for CP.
Myeloid neoplasms in the setting of chronic lymphocytic leukaemia/chronic lymphocytic leukaemia-like disease: a clinicopathological study of 66 cases comparing cases with prior history of treatment to those without
Authors: Luedke Catherine , Zhao Yue , McCracken Jenna , Maule Jake , Yang Lian-He , Jug Rachel , Galeotti Jonathan , Siddiqi Imran , Gong Jerald , Lu Chuanyi Mark , Wang Endi
Published: February 2021

Aims

Myeloid neoplasms occur in the setting of chronic lymphocytic leukaemia (CLL)/CLL-like disease. The underlying pathogenesis has not been elucidated.

Methods

Retrospectively analysed 66 cases of myeloid neoplasms in patients with CLL/CLL-like disease.

Results

Of these, 33 patients (group 1) had received treatment for CLL/CLL-like disease, while the other 33 patients (group 2) had either concurrent diagnoses or untreated CLL/CLL-like disease before identifying myeloid neoplasms. The two categories had distinct features in clinical presentation, spectrum of myeloid neoplasm, morphology, cytogenetic profile and clinical outcome. Compared with group 2, group 1 demonstrated a younger age at the diagnosis of myeloid neoplasm (median, 65 vs 71 years), a higher fraction of myelodysplastic syndrome (64% vs 36%; OR: 3.1; p<0.05), a higher rate of adverse unbalanced cytogenetic abnormalities, including complex changes, −5/5q- and/or −7/7q- (83% vs 28%; OR: 13.1; p<0.001) and a shorter overall survival (median, 12 vs 44 months; p<0.05).

Conclusions

Myeloid neoplasm in the setting of CLL/CLL-like disease can be divided into two categories, one with prior treatment for CLL/CLL-like disease and the other without. CLL-type treatment may accelerate myeloid leukaemogenesis. The risk is estimated to be 13-fold higher in patients with treatment than those without. The causative agent could be attributed to fludarabine in combination with alkylators, based on the latency of myeloid leukaemogenesis and the cytogenetic profile.
Pandemic prioritarianism
Authors: Nielsen Lasse
Published: February 2021

Prioritarianism pertains to the generic idea that it matters more to benefit people, the worse off they are, and while prioritarianism is not uncontroversial, it is considered a generally plausible and widely shared distributive principle often applied to healthcare prioritisation. In this paper, I identify social justice prioritarianism, severity prioritarianism and age-weighted prioritarianism as three different interpretations of the general prioritarian idea and discuss them in light of the effect of pandemic consequences on healthcare priority setting. On this analysis, the paper arrives at the following three conclusions: (1) that we have strong prioritarian reasons for special concern about the vulnerable and socially disadvantaged in reference to pandemic effects, (2) that severity of illness is an important factor in identifying the worse off in priority setting but that this must not over-ride the special priority to the socially disadvantaged and (3) that the maximisation rationale of the age-weighted view runs against the core prioritarian idea, and the age-weighted prioritarianism is thus unfitting as a prioritarian response to the COVID-19 case.
Assessment of risk compensation following use of the dapivirine vaginal ring in southwestern Uganda
Authors: Kusemererwa Sylvia , Abaasa Andrew , Kabarambi Anita , Onyango Martin , Mugisha Joseph Okello
Published: February 2021

Objectives

Participation in HIV prevention trials could trigger risk compensation among participants. We evaluated potential risk compensation following use of a vaginal ring microbicide by women in a phase III trial in southwestern Uganda.

Methods

We used markers of sexual risk behaviour documented on standardised questionnaires, tested for STIs at baseline and quarterly for 2 years. Risk compensation was defined as a significant increase (trend p<0.05) in the proportion of women reporting risky sexual behaviour or a diagnosed STI between baseline and end of follow-up.

Results

Between September 2013 and December 2016, 197 women (active arm: n=132 and placebo: n=65) were enrolled at the Masaka site. There were decreases in all markers of sexual risk behaviour with statistically significant decreases in only the proportion of women reporting ≥2 sexual partners, p=0.026 and those diagnosed withTrichomonas vaginalisp<0.001 and orNeisseria gonorrhoeaep<0.001

Conclusions

No evidence of risk compensation was observed in this trial.

Trial registration number

NCT01539226.
Identifying patients at risk of post-discharge complications related to COVID-19 infection
Authors: Hall Jocelin , Myall Katherine , Lam Jodie L , Mason Thomas , Mukherjee Bhashkar , West Alex , Dewar Amy
Published: February 2021

SARS-CoV-2 infection is a multisystem disease with post-discharge sequelae. We report early follow-up data from one UK hospital of the initial 200 hospital inpatients with slow recovery from the condition. At 4 weeks post-discharge, 321/957 survivors (34%) had persistent symptoms. A structured outpatient clinical assessment protocol was designed, and outcomes from the first 200 patients seen 4–6 weeks post-discharge are presented here. In 80/200 (40%), we identified at follow-up a cardiorespiratory cause of breathlessness, including persistent parenchymal abnormality (64 patients), pulmonary embolism (four patients) and cardiac complications (eight patients). These findings occurred both in patients who had intensive care unit (ICU) admissions and those who had been managed on the ward, although patients requiring ICU admissions were more likely to have a significant cardiorespiratory cause found for their breathlessness, risk ratio 2.8 (95% CI 1.5 to 5.1).
Essential role of smooth muscle Rac1 in severe asthma-associated airway remodelling
Authors: Dilasser Florian , Rose Lindsay , Hassoun Dorian , Klein Martin , Rousselle Morgane , Brosseau Carole , Guignabert Christophe , Taillé Camille , Dombret Marie Christine , Di Candia Leonarda , Heddebaut Nicolas , Bouchaud Gregory , Pretolani Marina , Magnan Antoine , Loirand Gervaise , Sauzeau Vincent
Published: February 2021

Background

Severe asthma is a chronic lung disease characterised by inflammation, airway hyperresponsiveness (AHR) and airway remodelling. The molecular mechanisms underlying uncontrolled airway smooth muscle cell (aSMC) proliferation involved in pulmonary remodelling are still largely unknown. Small G proteins of the Rho family (RhoA, Rac1 and Cdc42) are key regulators of smooth muscle functions and we recently demonstrated that Rac1 is activated in aSMC from allergic mice. The objective of this study was to assess the role of Rac1 in severe asthma-associated airway remodelling.

Methods and results

Immunofluorescence analysis in human bronchial biopsies revealed an increased Rac1 activity in aSMC from patients with severe asthma compared with control subjects. Inhibition of Rac1 by EHT1864 showed that Rac1 signalling controlled human aSMC proliferation induced by mitogenic stimuli through the signal transducer and activator of transcription 3 (STAT3) signalling pathway. In vivo, specific deletion of Rac1 in SMC or pharmacological inhibition of Rac1 by nebulisation of NSC23766 prevented AHR and aSMC hyperplasia in a mouse model of severe asthma. Moreover, the Rac1 inhibitor prevented goblet cell hyperplasia and epithelial cell hypertrophy whereas treatment with corticosteroids had less effect. Nebulisation of NSC23766 also decreased eosinophil accumulation in the bronchoalveolar lavage of asthmatic mice.

Conclusion

This study demonstrates that Rac1 is overactive in the airways of patients with severe asthma and is essential for aSMC proliferation. It also provides evidence that Rac1 is causally involved in AHR and airway remodelling. Rac1 may represent as an interesting target for treating both AHR and airway remodelling of patients with severe asthma.
Push-pull type Co(III)corroles: Synthesis, electronic structure and electrochemical catalysis
Authors: Niu Yingjie , Zhu Weihua , Mack John , Dubazana Nadine , Nyokong Tebello , Fu Bo , Xu Haijun , Liang Xu
Published: February 2021

The rational design and preparation of three A2B type Co(III)triarylcorroles with push- and pull-substituents are reported. The structure-property relationships were identified by comparing their optically spectroscopic and electrochemical properties to trends predicted in DFT and TD-DFT calculations. The results demonstrate that the Co(III)triarylcorroles are highly efficient catalysts for electrocatalyzed hydrogen evolutions (HERs) and oxygen reductions (ORRs), and that their reactivity can be modulated by changing the meso-B-substituent of the Co(III)Corroles.
The facile preparation of porphyrin based hierarchical micro/nano assemblies and their visible light photocatalytic activity
Authors: Zhang Dingwa , Huang Xueren , Huang Jiangen , Li Yuting , Cai Jinhua
Published: February 2021

Porphyrin nanostructures are widely used in the field of visible light catalysis due to their superior light absorption properties and good controllability in size, shape and function. In this paper, the development of various morphologies in three types of porphyrins with three different phenyl substituents (designated as H2TTP, H2TPP and H2TCPP, respectively) is demonstrated. The formation mechanism proposed was based on the evolution of morphology as functions of molecular structure and solvent mixture. These nano/micro assemblies are well characterized by SEM, IR, UV-vis, X-ray diffraction and photoelectric conversion. The photocatalytic oxidation reactions under visible light irradiation of 1,5-dihydroxynaphthalene (DHN) in water is utilized to evaluate the photoactivity of the as-prepared porphyrin assemblies. The photocatalytic results indicate that the obtained porphyrin assemblies exhibit enhanced visible-light photocatalytic activity. In addition, the photocatalyst is easy to separate and recover, and has good stability. The possible photocatalytic degradation mechanism of DHN by the porphyrins nanopolyhedron photocatalyst was also proposed.
Zinc-Doped Carbon Dots as Effective Blue-Light-Activated Antibacterial Agent
Authors: Liu Dongning , Yang Mingxi , Liu Xinchan , Yu Weixian
Published: February 2021

In view of the emergence and infection of drug-resistant bacteria, it is of great significance to develop new antibacterial materials. Carbon dots (CDs), which are carbon nanoparticles with surface passivation of abundant functional groups, have photoluminescent and photocatalytic properties like conventional nanoscale semiconductors but with low toxicity and good biocompatibility. This study was designed to investigate the antimicrobial effects of zinc-doped carbon dots (Zn-CDs) in combination with blue light. Analysis of conducted antibacterial tests on Staphylococcus aureus (S. aureus) and Streptococcus mutans (S. mutans) showed the bactericidal effect of reactive oxygen species (ROS) which was produced by excited Zn-CDs by 10[Formula: see text]min excitation of blue light. In addition, we also explored the cell cytotoxicity of Zn-CDs. This work indicated that the Zn-CDs not only were low cytotoxicity with the 80% of the relative increment rate of cells, but possessed the capability of photo-induced inhibition of bacteria growth and biofilm formation. Therefore, the CDs have great potential in serving as a new kind of photocatalyst, which can be applied to the photodynamic antibacterial treatment for reducing the possibilities of the development of microbial resistances.
Anatomy of Distal Articular Surface of Hamate Bone, A Cadaveric Study
Authors: Anantavorasakul Navapong , Sutthiwongkit Thanat , Kittithamvongs Piyabuth , Malungpaishrope Kanchai , Uerpairojkit Chairoj
Published: February 2021

Background: Hemi-hamate arthroplasty is one of the treatment options for dorsal proximal interphalangeal joint fracture dislocation. Many studies reported favorable outcomes. However, some long term studies demonstrated the degenerative change of PIP joint. The articular mismatch of the hemi-hamate autograft might play an important role of this complication.

Methods: We studied the anatomy of distal articular surface of the hamate bone in embalmed hamate bones. The anatomy of distal articular surface and dimensions of the hamate bone were measured and recorded.

Results: Seventy hamate bones were dissected out from embalmed cadavers and included in this study. The mean angle of the 4th metacarpal articulation was 85.54 degrees (SD = 3.53) and mean angle of the 5th metacarpal articulation was 95.51 degrees (SD = 3.57). The inter-articular ridge was approximately 5 degrees radial inclination.

Conclusions: The inter-articular ridge of distal articular surface was approximately 5 degrees radial inclination. In order to minimize the graft mismatch, we recommend making the bone cut with the saw blade tilted to radial side 5 degrees to achieve better alignment of inter-articular ridge of the graft.
The Myth of the New Cold War
Authors: Shuyong Guo , Boran Li
Published: February 2021

With the changes of international order and the deterioration of China–US relations, it has been argued that a new Cold War is approaching. However, this view does not comprehensively consider the differences between the current world and the world during the Cold War era. In fact, the political and economic basis of a new Cold War is far from mature, and China and America have gained abundant experiences of risk management. In addition, China is also very different from the Soviet Union. All of these elements determined that China and US will not necessarily have a new Cold War. However, some potential risks that may push China and US crash with each other should be carefully considered.
A Novel Voltammetric Approach For The Quantification of Aflatoxin B1 Using a Bismuth-Modified Electrode
Authors: Hernández-Hernández Aldahir A. , Castañeda-Ovando Araceli , Mendoza-Huizar Luis H. , Franco-Guzmán Miriam , Meneses-Pimentel Karla X. , Galán Vidal Carlos A. , Páez-Hernández María E. , Álvarez Romero G. A.
Published: February 2021

Aflatoxins are high-toxic secondary metabolites of Aspergillus fungus, which contaminate food at trace levels. Promising voltammetric methods were developed using mercury electrodes, however, they have negative effects on the environment. This work proposes the development and optimization of a differential pulse voltammetric methodology for the quantification of Aflatoxin B1 through bismuth film electrodes by the reduction of aflatoxin. Aflatoxin B1 reduction is controlled by its diffusion towards the electrode’s surface. Optimal conditions for the preparation of the bismuth film and differential pulse voltammetry were obtained by Box-Behnken experimental designs, considering the maximization of the Aflatoxin B1 cathodic peak current. The LOD and LOQ resulted to be 11.2 ng l−1and 37.3 ng l−1respectively. The values for the reproducibility and repeatability as %RSD, using a 38.46 ng l−1solution of Aflatoxin B1 for the measurements, were 5.3% and 4.6%, respectively. The proposed methodology was statistically validated using certified Aflatoxin B1 standard solutions and milk samples successfully analyzed, demonstrating that the proposed methodology represents a novel, low-cost, environmentally-friendly approach for the quantification of Aflatoxin B1.
Stability of Atomically Dispersed Fe–N–C ORR Catalyst in Polymer Electrolyte Fuel Cell Environment
Authors: Ahluwalia R. K. , Wang X. , Osmieri L. , Peng J-K , Cetinbas C. F. , Park J. , Myers D. J. , Chung H. T. , Neyerlin K. C.
Published: February 2021

We have investigated the durability of a platinum group metal (PGM-)free Fe–N–C catalyst in which the Fe sites are atomically dispersed (AD), and found it to be quite stable in standard accelerated stress test (AST) cycles normally used for low-PGM catalysts: a square wave with 0.6 V lower potential limit (LPL)—0.95 V upper potential limit (UPL) with 3-s holds at UPL and LPL in H2/N2, at 1.5 atm, 80 °C and 100% RH. Considering the metrics normally employed to characterize the durability of the low-PGM catalysts after 30,000 AST cycles, this PGM-free catalyst lost <50% catalyst activity, <50% H2/air performance at 0.8 V, and 40 mV at 1.5 A cm−2. However, it is less stable in H2/air, losing ∼50% catalyst activity after just 7.5 h of polarization measurements (load cycles). In combined cycles, the majority of the loss in catalyst activity occurred during the load cycles in H2/air rather than AST cycles in H2/N2. We have concluded that, unlike low-PGM catalysts that lose electrochemically active surface area (ECSA) through potential cycling-induced processes, (AD)Fe–N–C catalysts degrade by processes associated with the presence of oxygen.
Review—Aptamer-Based Electrochemical Sensing Strategies for Breast Cancer
Authors: Sunday Christopher Edozie , Chowdhury Mahabubur
Published: February 2021

The importance of developing molecular diagnostic aimed at detecting low concentrations of protein biomarkers, that are present in early stages of breast cancer cannot be over emphasised. This is driven in large part by the need to fabricate minimally- or non-invasive, portable, rapid and less expensive testing technologies. In this context, the capability of electrochemical methods combined with the customizability of aptamers to specifically bind various targets in complex biological fluids has realized significant impact. Aptamers are relatively less sensitive to temperature variations, and their small 3-dimensional nucleic acid structure supports specific binding with target molecules. Consequent upon these clinically favorable properties, different aptamer-based electrochemical sensing strategies have been fabricated over the decades, and various transducing techniques are classified based on the signals generated. Here we review the recent advances of these strategies for the next generation of breast cancer diagnostics, with emphasis on their challenges, possible solutions and diagnostic prospects.