bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroprotection by WldS depends on retinal ganglion cell type and age in glaucoma
Authors: Risner Michael L. , Pasini Silvia , McGrady Nolan R. , D’Alessandro Karis B. , Yao Vincent , Cooper Melissa L. , Calkins David J. 
Published: June 2021

Abstract
Background
Early challenges to axonal physiology, active transport, and ultrastructure are endemic to age-related neurodegenerative disorders, including those affecting the optic nerve. Chief among these, glaucoma causes irreversible vision loss through sensitivity to intraocular pressure (IOP) that challenges retinal ganglion cell (RGC) axons, which comprise the optic nerve. Early RGC axonopathy includes distal to proximal progression that implicates a slow form of Wallerian degeneration. In multiple disease models, including inducible glaucoma, expression of the slow Wallerian degeneration (WldS) allele slows axon degeneration and confers protection to cell bodies.

Methods
Using an inducible model of glaucoma along with whole-cell patch clamp electrophysiology and morphological analysis, we tested if WldS also protects RGC light responses and dendrites and, if so, whether this protection depends upon RGC type. We induced glaucoma in young and aged mice to determine if neuroprotection by WldS on anterograde axonal transport and spatial contrast acuity depends on age.

Results
We found WldS protects dendritic morphology and light-evoked responses of RGCs that signal light onset (αON-Sustained) during IOP elevation. However, IOP elevation significantly reduces dendritic complexity and light responses of RGCs that respond to light offset (αOFF-Sustained) regardless of WldS. As expected, WldS preserves anterograde axon transport and spatial acuity in young adult mice, but its protection is significantly limited in aged mice.

Conclusion
The efficacy of WldS in conferring protection to neurons and their axons varies by cell type and diminishes with age.
“Don’t Phos Over Tau”: recent developments in clinical biomarkers and therapies targeting tau phosphorylation in Alzheimer’s disease and other tauopathies
Authors: Xia Yuxing , Prokop Stefan , Giasson Benoit I. 
Published: June 2021

AbstractPhosphorylation is one of the most prevalent post-translational modifications found in aggregated tau isolated from Alzheimer’s disease (AD) patient brains. In tauopathies like AD, increased phosphorylation or hyperphosphorylation can contribute to microtubule dysfunction and is associated with tau aggregation. In this review, we provide an overview of the structure and functions of tau protein as well as the physiologic roles of tau phosphorylation. We also extensively survey tau phosphorylation sites identified in brain tissue and cerebrospinal fluid from AD patients compared to age-matched healthy controls, which may serve as disease-specific biomarkers. Recently, new assays have been developed to measure minute amounts of specific forms of phosphorylated tau in both cerebrospinal fluid and plasma, which could potentially be useful for aiding clinical diagnosis and monitoring disease progression. Additionally, multiple therapies targeting phosphorylated tau are in various stages of clinical trials including kinase inhibitors, phosphatase activators, and tau immunotherapy. With promising early results, therapies that target phosphorylated tau could be useful at slowing tau hyperphosphorylation and aggregation in AD and other tauopathies.
“I try the one that they say is good.” - factors influencing choice of health care provider and pathways to diabetes care for Syrian refugees in Lebanon
Authors: Haderer Flora , Venables Emilie , van Olmen Josefien , Orcutt Miriam , Ghassibe-Sabbagh Michella , van den Boogaard Wilma 
Published: June 2021

Abstract
Background
Navigating health systems in host countries can be a challenge for refugees, particularly in a multi-provider system such as Lebanon. Syrian refugees in Lebanon face a high burden of Non-Communicable Diseases (NCDs) including diabetes mellitus. Evidence on how refugees navigate the health system is essential to improve provision of NCD services. We conducted a qualitative study amongst Syrian diabetes patients visiting Médecins Sans Frontières (MSF) clinics in one urban and one rural setting in Lebanon to explore factors influencing choice of and pathways to diabetes care.

Methods
In-depth interviews were conducted with male and female adult participants with DM type 1 or type 2 who were receiving treatment at MSF clinics. Participants were recruited using convenience sampling. Interviews were conducted in Arabic and directly transcribed and translated into English. Data were coded in NVivo and analyzed using an inductive thematic approach.

Results
A total of 29 in-depth interviews were conducted with 13 men and 16 women. Knowledge and understanding of diabetes management differed among participants. Syrian refugees in Lebanon gathered information about health services for diabetes largely from social networks of family and peers rather than through formal means. Pathways to care included different combinations of providers such as clinics, pharmacists and informal providers.

Conclusions
Syrian refugees with diabetes in Lebanon face considerable challenges in navigating the health care system due to their vulnerable status and limited knowledge of the host country systems. To ensure access to care for diabetes, efforts need to be made to support patients’ orientation in the Lebanese health system.
Antibody-drug conjugates for the treatment of lymphoma: clinical advances and latest progress
Authors: Chu Yurou , Zhou Xiangxiang , Wang Xin 
Published: June 2021

AbstractAntibody-drug conjugates (ADCs) are a promising class of immunotherapies with the potential to specifically target tumor cells and ameliorate the therapeutic index of cytotoxic drugs. ADCs comprise monoclonal antibodies, cytotoxic payloads with inherent antitumor activity, and specialized linkers connecting the two. In recent years, three ADCs, brentuximab vedotin, polatuzumab vedotin, and loncastuximab tesirine, have been approved and are already establishing their place in lymphoma treatment. As the efficacy and safety of ADCs have moved in synchrony with advances in their design, a plethora of novel ADCs have garnered growing interest as treatments. In this review, we provide an overview of the essential elements of ADC strategies in lymphoma and elucidate the up-to-date progress, current challenges, and novel targets of ADCs in this rapidly evolving field.
Standardized post-resuscitation damage assessment of two mechanical chest compression devices: a prospective randomized large animal trial
Authors: Ruemmler Robert , Stein Jakob , Duenges Bastian , Renz Miriam , Hartmann Erik Kristoffer 
Published: June 2021

Abstract
Background
Mechanical chest compression devices are accepted alternatives for cardiopulmonary resuscitation (CPR) under specific circumstances. Current devices lack prospective and comparative data on their specific cardiovascular effects and potential for severe thoracic injuries.

Objectives
To compare CPR effectiveness and thoracic injuries of two mechanical chest compression devices in pigs.

Study design
Prospective randomised trial.

Animals
Eighteen male German landrace pigs.

Methods
Ventricular fibrillation was induced in anaesthetised and instrumented pigs and the animals were randomised into two intervention groups. Mechanical CPR was initiated by means of LUCAS™ 2 (mCCD1) or Corpuls™ cpr (mCCD2) device. Advanced life support was applied for a maximum of 10 cycles and animals achieving ROSC were monitored for 8 h. Ventilation/perfusion measurements were performed and blood gas analyses were taken. Thoracic injuries were assessed via a standardised damage score.

Results
Five animals of the mCCD1 group and one animal of the mCCD2 group achieved ROSC (p = 0.048). Only the mCCD1 animals survived until the end of the monitoring period (p < 0.01). MCCD1 animals showed less pulmonary shunt (p = 0.025) and higher normal V/Q (p = 0.017) during CPR. MCCD2 animals showed significantly more severe thoracic injuries (p = 0.046).

Conclusion
The LUCAS 2 device shows superior resuscitation outcomes and less thoracic injuries compared to Corpuls cpr when used for experimental CPR in juvenile pigs. Researchers should be aware that different mCCDs for experimental studies may significantly influence the respective outcome of resuscitation studies and affect comparability of different trials. Controlled human and animal CPR studies and a standardised post-resuscitation injury evaluation could help to confirm potential hazards.

Trial registration
Trial approval number: G16–1-042-E4.
Prevalence of SARS-CoV-2 infection in Italian pediatric population: a regional seroepidemiological study
Authors: Comar Manola , Benvenuto Simone , Lazzerini Marzia , Fedele Giorgio , Barbi Egidio , Amaddeo Alessandro , Risso Francesco Maria , Strajn Tamara , Di Rocco Paola , Stefanelli Paola , Rezza Giovanni 
Published: June 2021

Abstract
Background
Data on the effective burden of the SARS-CoV-2 pandemic in pediatric population are very limited, mostly because of the higher rate of asymptomatic or paucisymptomatic cases among children. Updated data on COVID-19 prevalence are needed for their relevance in public health and for infection control policies. In this single-centre cross-sectional study we aimed to assess prevalence of SARS-CoV-2 infection through IgG antibodies detection in an Italian pediatric cohort.

Methods
The study was conducted in January 2021 among both inpatients and outpatients referring to Research Institute for Maternal and Child Health “Burlo Garofolo” in Trieste, Friuli Venezia-Giulia, Italy, who needed for blood test for any reason. Collected samples were sent to Italian National Institute of Health for analysis through chemiluminescent immunoassay (CLIA).

Results
One hundred sixty-nine patients were included in the study, with a median age of 10.5 ± 4.1 years, an equal distribution for sex (49.7% female patients), and a 55.6% prevalence of comorbidities. Prevalence of anti-SARS-CoV-2 trimeric Spike protein IgG antibodies was 9.5% (n = 16), with a medium titre of 482.3 ± 387.1 BAU/mL. Having an infected cohabitant strongly correlated with IgG positivity (OR 23.83, 95% CI 7.19–78.98, p < 0.0001), while a cohabitant healthcare worker wasn’t associated with a higher risk (OR 1.53, 95% CI 0.4–5.86, p 0.46). All of the 5 patients who had previously tested positive to a nasopharyngeal swab belonged to the IgG positive group, with a 3-month interval from the infection at most.

Conclusion
We assessed a 9.5% SARS-CoV-2 seroprevalence in a pediatric cohort from Friuli Venezia-Giulia region in January 2021, showing a substantial increase after the second peak of the pandemic occurred starting from October 2020, compared to 1% prevalence observed by National Institute of Statistics (ISTAT) in July 2020.
Efficacy of pediatric integrative manual therapy in positional plagiocephaly: a randomized controlled trial
Authors: Pastor-Pons Iñaki , Lucha-López María Orosia , Barrau-Lalmolda Marta , Rodes-Pastor Iñaki , Rodríguez-Fernández Ángel Luis , Hidalgo-García César , Tricás-Moreno Jose Miguel 
Published: June 2021

Abstract
Background
Positional plagiocephaly frequently affects healthy babies. It is hypothesized that manual therapy tailored to pediatrics is more effective in improving plagiocephalic cranial asymmetry than just repositioning and sensory and motor stimulation.

Methods
Thirty-four neurologically healthy subjects aged less than 28 weeks old with a difference of at least 5 mm between cranial diagonal diameters were randomly distributed into 2 groups. For 10 weeks, the pediatric integrative manual therapy (PIMT) group received manual therapy plus a caregiver education program, while the controls received the same education program exclusively. Cranial shape was evaluated using anthropometry; cranial index (CI) and cranial vault asymmetry index (CVAI) were calculated. Parental perception of change was assessed using a visual analogue scale (− 10 cm to + 10 cm).

Results
CVAI presented a greater decrease in PIMT group: 3.72 ± 1.40% compared with 0.34 ± 1.72% in the control group (p = 0.000). CI did not present significant differences between groups. Manual therapy led to a more positive parental perception of cranial changes (manual therapy: 6.66 ± 2.07 cm; control: 4.25 ± 2.31 cm; p = 0.004).

Conclusion
Manual therapy plus a caregiver education program improved CVAI and led to parental satisfaction more effectively than solely a caregiver education program.

Trial registration
Trial registration number: NCT03659032; registration date: September 1, 2018. Retrospectively registered.
Association between maternal iron supplementation and newborn birth weight: a quantile regression analysis
Authors: Shi Guoshuai , Zhang Zhuo , Ma Lu , Zhang Binyan , Dang Shaonong , Yan Hong 
Published: June 2021

Abstract
Objective
Our study aimed to explore the association between maternal iron supplementation and newborn birth weight (BW) in Shaanxi Province using quantile regression (QR).

Method
The data used in this study were derived from a large cross-sectional survey of a population in Shaanxi Province, Northwest China. A total of 28,209 women and their infants were selected using a stratified multistage random sampling method. The effect of iron supplementation on the newborn BW was assessed by a multiple linear regression model and QR.

Results
A total of 5.15% of the women took iron supplements during pregnancy. Multiple linear regression showed that the iron supplementation during pregnancy had positive effects on the BW, with an average increase of 43.07 g (β = 43.07, t = 3.55, and p < 0.001). The QR showed that the iron supplementation during pregnancy was associated with an increased newborn BW from very low to higher percentiles (quantiles: 0 ~ 0.40), with the β ranging from 136.51 to 43.86. As the percentiles of the BW increased, the neonatal BW gain gradually declined in the iron supplementation group compared with the group that did not receive iron supplementation (quantiles: 0 ~ 0.40, with the β ranging from 136.51 to 43.86). Iron supplementation was more effective among women who suffered from anemia during pregnancy (β = 45.84, t = 2.05, and p = 0.04; quantiles: 0 ~ 0.15, 0.30, 0.80, with β ranging from 150.00 to 39.29) than it was in any other group (β = 38.18, t = 2.62, and p = 0.009; quantiles: 0 ~ 0.15, with β ranging from 133.33 to 28.32).

Conclusions
Iron supplementation during pregnancy is associated with an increased newborn BW, and the effect was more obvious in the newborns with the lower BW and newborns whose mothers suffered from anemia during pregnancy.
Circulating immune cell populations related to primary breast cancer, surgical removal, and radiotherapy revealed by flow cytometry analysis
Authors: Cattin Sarah , Fellay Benoît , Calderoni Antonello , Christinat Alexandre , Negretti Laura , Biggiogero Maira , Badellino Alberto , Schneider Anne-Lise , Tsoutsou Pelagia , Pellanda Alessandra Franzetti , Rüegg Curzio 
Published: June 2021

Abstract
Background
Advanced breast cancer (BC) impact immune cells in the blood but whether such effects may reflect the presence of early BC and its therapeutic management remains elusive.

Methods
To address this question, we used multiparametric flow cytometry to analyze circulating leukocytes in patients with early BC (n = 13) at the time of diagnosis, after surgery, and after adjuvant radiotherapy, compared to healthy individuals. Data were analyzed using a minimally supervised approach based on FlowSOM algorithm and validated manually.

Results
At the time of diagnosis, BC patients have an increased frequency of CD117+CD11b+ granulocytes, which was significantly reduced after tumor removal. Adjuvant radiotherapy increased the frequency of CD45RO+ memory CD4+ T cells and CD4+ regulatory T cells. FlowSOM algorithm analysis revealed several unanticipated populations, including cells negative for all markers tested, CD11b+CD15low, CD3+CD4−CD8−, CD3+CD4+CD8+, and CD3+CD8+CD127+CD45RO+ cells, associated with BC or radiotherapy.

Conclusions
This study revealed changes in blood leukocytes associated with primary BC, surgical removal, and adjuvant radiotherapy. Specifically, it identified increased levels of CD117+ granulocytes, memory, and regulatory CD4+ T cells as potential biomarkers of BC and radiotherapy, respectively. Importantly, the study demonstrates the value of unsupervised analysis of complex flow cytometry data to unravel new cell populations of potential clinical relevance.
Temperature and food sources influence subadult development and blood-feeding response of Culicoides obsoletus (sensu lato) under laboratory conditions
Authors: Van den Eynde Claudia , Sohier Charlotte , Matthijs Severine , De Regge Nick 
Published: June 2021

Abstract
Background
Culicoides obsoletus (s.l.) is the most abundant Culicoides species in northern Europe and an important vector of bluetongue virus and Schmallenberg virus. Nevertheless, information on its subadult life stages remains scarce and no laboratory-reared colony exists.

Methods
C. obsoletus (s.l.) adults were collected in Belgium and transferred to the laboratory in an attempt to establish a laboratory-reared colony. C. obsoletus (s.l.) were reared from eggs to adults at different temperatures (28 °C, 24 °C, 20/16 °C) and under different food regimes.

Results
The most suitable temperature for rearing seemed to be 24 °C for most developmental parameters, but resulted in a biased 3:1 male/female sex ratio. The latter could be optimized to a 1:1 sex ratio when a 20/16 °C day/night temperature gradient was applied, but rearing at these low temperature conditions resulted in significantly lower egg hatching and pupation rates and a longer subadult development time. Independent of the rearing temperature, adding dung as an additional food source during larval development resulted in a significantly higher adult emergence rate and a decrease in subadult development time. Furthermore, blood-feeding rates of field-collected C. obsoletus (s.l.) were compared for different blood sources and feeding systems. The overall blood-feeding success was low and only successful with cotton pledgets (2.7% blood-fed midges) and through a membrane system with chicken skin (3.5% blood-fed midges). Higher feeding rates were obtained on cattle blood compared to sheep blood.

Conclusions
These results will help us to determine the necessary conditions to rear a viable laboratory colony of this important vector species, although further optimization is still required.

Graphical abstract
Recent aspects on epidemiology, clinical disease, and genetic diversity of Toxoplasma gondii infections in Australasian marsupials
Authors: Dubey Jitender P. , Murata Fernando H. A. , Cerqueira-Cézar Camila K. , Kwok Oliver C. H. , Su Chunlei , Grigg Michael E. 
Published: June 2021

AbstractBackgroundToxoplasma gondiiinfections are common in humans and animals worldwide. Among all intermediate hosts ofT. gondii, captive marsupials from Australia and New Zealand are highly susceptible to clinical toxoplasmosis. However, most free-range marsupials establish chronicT. gondiiinfection. Infected marsupial meat may serve as a source ofT. gondiiinfection for humans. Differences in mortality patterns in different species of kangaroos and other marsupials are not fully understood. Lifestyle, habitat, and the genotype ofT. gondiiare predicted to be risk factors. For example, koalas are rarely exposed toT. gondiibecause they live on treetops whereas wallabies on land are frequently exposed to infection.MethodsThe present review summarizes worldwide information on the prevalence of clinical and subclinical infections, epidemiology, and genetic diversity ofT. gondiiinfecting Australasian marsupials in their native habitat and among exported animals over the past decade. The role of genetic types ofT. gondiiand clinical disease is discussed.ResultsFatal toxoplasmosis has been diagnosed in captive Australasian marsupials in Argentina, Chile, China, Germany, Hungary, Japan, Spain, Turkey, and the USA. Most deaths occurred because of disseminated toxoplasmosis. Genetic characterization ofT. gondiistrains isolated from fatal marsupial infections identified Type III as well as atypical, nonclonal genotypes. Fatal toxoplasmosis was also diagnosed in free-ranging wombats (Vombatus ursinus) in Australia. Genetic characterization of DNA amplified directly from host tissues of subclinical culled kangaroos at slaughter identified many mixed-strain infections with both atypical and recombinant genotypes ofT. gondii.ConclusionsMost Australasian marsupials in their native land, Australia and New Zealand, have high prevalence ofT. gondii, and kangaroo meat can be a source of infection for humans if consumed uncooked/undercooked. The genotypes prevalent in kangaroos in Australia and New Zealand were genetically distinct from those isolated or genotyped from most macropods in the USA and other countries. Thus, clinical toxoplasmosis in marsupials imported from Australia is most likely to occur from infections acquired after importation.Graphical Abstract
Mosquito vector proteins homologous to α1-3 galactosyl transferases of tick vectors in the context of protective immunity against malaria and hypersensitivity to vector bites
Authors: Ramasamy Ranjan 
Published: June 2021

AbstractBackgroundAn epitope, Galα1-3Galβ1-4GlcNAc-R, termed α-gal, is present in glycoconjugates of New World monkeys (platyrrhines) and other mammals but not in hominoids and Old World monkeys (catarrhines). The difference is due to the inactivation of α1-3 galactosyl transferase (α1-3 GT) genes in catarrhines. Natural antibodies to α-gal are therefore developed in catarrhines but not platyrrhines and other mammals. Hypersensitivity reactions are commonly elicited by mosquito and tick vector bites. IgE antibodies against α-gal cause food allergy to red meat in persons who have been exposed to tick bites. Three enzymes synthesising the terminal α1-3-linked galactose in α-gal, that are homologous to mammalian α and β1-4 GTs but not mammalian α1-3 GTs, were recently identified in the tick vectorIxodes scapularis. IgG and IgM antibodies to α-gal are reported to protect against malaria because mosquito-derived sporozoites of malaria parasites express α-gal on their surface. This article explores the possibility that the α-gal in sporozoites are acquired from glycoconjugates synthesised by mosquitoes rather than through de novo synthesis by sporozoites.MethodsThe presence of proteins homologous to the three identified tick α1-3 GTs and mammalian α1-3 GTs in two important mosquito vectors,Aedes aegyptiandAnopheles gambiae, as well asPlasmodiummalaria parasites, was investigated by BLASTp analysis to help clarify the source of the α-gal on sporozoite surfaces.ResultsAnopheles gambiaeandAe. aegyptipossessed several different proteins homologous to the threeI. scapularisproteins with α1-3 GT activity, but not mammalian α1-3 GTs. The putative mosquito α1-3 GTs possessed conserved protein domains characteristic of glycosyl transferases. However, the genusPlasmodiumlacked proteins homologous to the threeI. scapularisproteins with α1-3 GT activity and mammalian α1-3 GTs.ConclusionsThe putative α1-3 GTs identified in the two mosquito vectors may synthesise glycoconjugates containing α-gal that can be transferred to sporozoite surfaces before they are inoculated into skin during blood feeding. The findings merit further investigation because of their implications for immunity against malaria, hypersensitivity to mosquito bites, primate evolution, and proposals for immunisation against α-gal.Graphical Abstract