bluuebunny/crossref_metadata_2025 huggingface dataset:
bsAS, an antisense long non-coding RNA, essential for correct wing development through regulation of blistered/DSRF isoform usage
Authors: Pérez-Lluch Sílvia , Klein Cecilia C. , Breschi Alessandra , Ruiz-Romero Marina , Abad Amaya , Palumbo Emilio , Bekish Lyazzat , Arnan Carme , Guigó Roderic
Published: December 2020

Natural Antisense Transcripts (NATs) are long non-coding RNAs (lncRNAs) that overlap coding genes in the opposite strand. NATs roles have been related to gene regulation through different mechanisms, including post-transcriptional RNA processing. With the aim to identify NATs with potential regulatory function during fly development, we generated RNA-Seq data inDrosophiladeveloping tissues and foundbsAS, one of the most highly expressed lncRNAs in the fly wing.bsASis antisense tobs/DSRF, a gene involved in wing development and neural processes.bsASplays a crucial role in the tissue specific regulation of the expression of thebs/DSRF isoforms. This regulation is essential for the correct determination of cell fate duringDrosophiladevelopment, asbsASknockouts show highly aberrant phenotypes. Regulation ofbsisoform usage bybsASis mediated by specific physical interactions between the promoters of these two genes, which suggests a regulatory mechanism involving the collision of RNA polymerases transcribing in opposite directions. Evolutionary analysis suggests thatbsASNAT emerged simultaneously to the long-short isoform structure ofbs, preceding the emergence of wings in insects.
Physiological and genetic convergence supports hypoxia resistance in high-altitude songbirds
Authors: Xiong Ying , Fan Liqing , Hao Yan , Cheng Yalin , Chang Yongbin , Wang Jing , Lin Haiyan , Song Gang , Qu Yanhua , Lei Fumin
Published: December 2020

Skeletal muscle plays a central role in regulating glucose uptake and body metabolism; however, highland hypoxia is a severe challenge to aerobic metabolism in small endotherms. Therefore, understanding the physiological and genetic convergence of muscle hypoxia tolerance has a potential broad range of medical implications. Here we report and experimentally validate a common physiological mechanism across multiple high-altitude songbirds that improvement in insulin sensitivity contributes to glucose homeostasis, low oxygen consumption, and relative activity, and thus increases body weight. By contrast, low-altitude songbirds exhibit muscle loss, glucose intolerance, and increase energy expenditures under hypoxia. This adaptive mechanism is attributable to convergent missense mutations in theBNIP3Lgene, andMETTL8gene that activatesMEF2Cexpression in highlanders, which in turn increases hypoxia tolerance. Together, our findings from wild high-altitude songbirds suggest convergent physiological and genetic mechanisms of skeletal muscle in hypoxia resistance, which highlights the potentially medical implications of hypoxia-related metabolic diseases.
Presence of pathogenic Leptospira spp. in the reproductive system and fetuses of wild boars (Sus scrofa) in Italy
Authors: Cilia Giovanni , Bertelloni Fabrizio , Piredda Ivana , Ponti Maria Nicoletta , Turchi Barbara , Cantile Carlo , Parisi Francesca , Pinzauti Paolo , Armani Andrea , Palmas Bruna , Noworol Malgorzata , Cerri Domenico , Fratini Filippo
Published: December 2020

Leptospirosis is a re-emerging and globally spread zoonosis caused by pathogenic genomospecies of Leptospira. Wild boar (Sus scrofa) are an important Leptospira host and are increasing in population all over Europe. The aim of this investigation was to evaluate Leptospira spp. infection in the reproductive systems of wild boar hunted in two Italian regions: Tuscany and Sardinia. From 231 animals, reproductive system tissue samples (testicles, epididymides, uteri) as well as placentas and fetuses were collected. Bacteriological examination and Real-Time PCR were performed to detect pathogenic Leptospira (lipL32 gene). Leptospires were isolated from the testicles and epididymides of one adult and two subadult wild boar. Four isolates from the two subadult males were identified as Leptospira interrogans serogroup Australis by MLST, whereas Leptospira kirschneri serogroup Grippotyphosa was identified from the adult testicles and epididymis. Using Real-Time PCR, 70 samples were positive: 22 testicles (23.16%) and 22 epididymides (23.16%), 10 uteri (7.35%), 3 placentas (6.66%), and 13 fetuses (28.88%). Amplification of the rrs2 gene identified L. interrogans and L. kirschneri species. The results from this investigation confirmed that wild boar represent a potential source of pathogenic Leptospira spp. Isolation of Leptospira serogroups Australis and Grippotyphosa from the male reproductive system and the positive Real-Time PCR results from both male and female samples could suggest venereal transmission, as already demonstrated in pigs. Furthermore, placentas and fetuses were positive for the lipL32 target, and this finding may be related to a possible vertical transmission of pathogenic Leptospira.
Serodiagnostic antigens of Clonorchis sinensis identified and evaluated by high-throughput proteogenomics
Authors: Cho Pyo Yun , Lee Ji-Yun , Kim Tae Im , Song Jin-Ho , Hong Sung-Jong , Yoo Won Gi , Tsuboi Takafumi , Ha Kwon-Soo , Jung Jae-Wan , Takeo Satoru , Han Eun-Taek , Sripa Banchob , Hong Sung-Tae , Chai Jong-Yil , Nam Ho-Woo , Pak Jhang Ho , Kim Tong-Soo
Published: December 2020

Clonorchiasis caused by Clonorchis sinensis is endemic in East Asia; approximately 15 million people have been infected thus far. To diagnose the infection, serodiagnostic tests with excellent functionality should be performed. First, 607 expressed sequence tags encoding polypeptides with a secretory signal were expressed into recombinant proteins using an in vitro translation system. By protein array-based screening using C. sinensis-infected sera, 18 antigen candidate proteins were selected and assayed for cross-reactivity against Opisthorchis viverrini-infected sera. Of the six antigenic proteins selected, four were synthesized on large scale in vitro and evaluated for antigenicity against the flukes-infected human sera using ELISA. CsAg17 antigen showed the highest sensitivity (77.1%) and specificity (71.2%). The sensitivity and specificity of the bacterially produced CsAg17-28GST fusion antigen was similar to those of CsAg17 antigen. CsAg17 antigen can be used to develop point-of-care serodiagnostic tests for clonorchiasis.
A novel circulating tamiami mammarenavirus shows potential for zoonotic spillover
Authors: Moreno Hector , Rastrojo Alberto , Pryce Rhys , Fedeli Chiara , Zimmer Gert , Bowden Thomas A. , Gerold Gisa , Kunz Stefan
Published: December 2020

A detailed understanding of the mechanisms underlying the capacity of a virus to break the species barrier is crucial for pathogen surveillance and control. New World (NW) mammarenaviruses constitute a diverse group of rodent-borne pathogens that includes several causative agents of severe viral hemorrhagic fever in humans. The ability of the NW mammarenaviral attachment glycoprotein (GP) to utilize human transferrin receptor 1 (hTfR1) as a primary entry receptor plays a key role in dictating zoonotic potential. The recent isolation of Tacaribe and lymphocytic choriominingitis mammarenaviruses from host-seeking ticks provided evidence for the presence of mammarenaviruses in arthropods, which are established vectors for numerous other viral pathogens. Here, using next generation sequencing to search for other mammarenaviruses in ticks, we identified a novel replication-competent strain of the NW mammarenavirus Tamiami (TAMV-FL), which we found capable of utilizing hTfR1 to enter mammalian cells. During isolation through serial passaging in mammalian immunocompetent cells, the quasispecies of TAMV-FL acquired and enriched mutations leading to the amino acid changes N151K and D156N, within GP. Cell entry studies revealed that both substitutions, N151K and D156N, increased dependence of the virus on hTfR1 and binding to heparan sulfate proteoglycans. Moreover, we show that the substituted residues likely map to the sterically constrained trimeric axis of GP, and facilitate viral fusion at a lower pH, resulting in viral egress from later endosomal compartments. In summary, we identify and characterize a naturally occurring TAMV strain (TAMV-FL) within ticks that is able to utilize hTfR1. The TAMV-FL significantly diverged from previous TAMV isolates, demonstrating that TAMV quasispecies exhibit striking genetic plasticity that may facilitate zoonotic spillover and rapid adaptation to new hosts.
New features on the survival of human-infective Trypanosoma rangeli in a murine model: Parasite accumulation is observed in lymphoid organs
Authors: Ferreira Luciana de Lima , Araújo Fernanda Fortes de , Martinelli Patricia Massara , Teixeira-Carvalho Andrea , Alves-Silva Juliana , Guarneri Alessandra Aparecida
Published: December 2020

Trypanosoma rangeli is a non-pathogenic protozoan parasite that infects mammals, including humans, in Chagas disease-endemic areas of South and Central America. The parasite is transmitted to a mammalian host when an infected triatomine injects metacyclic trypomastigotes into the host′s skin during a bloodmeal. Infected mammals behave as parasite reservoirs for several months and despite intensive research, some major aspects of T. rangeli-vertebrate interactions are still poorly understood. In particular, many questions still remain unanswered, e.g. parasite survival and development inside vertebrates, as no parasite multiplication sites have yet been identified. The present study used an insect bite transmission strategy to investigate whether the vector inoculation spot in the skin behave as a parasite-replication site. Histological data from the skin identified extracellular parasites in the dermis and hypodermis of infected mice in the first 24 hours post-infection, as well as the presence of inflammatory infiltrates in a period of up to 7 days. However, qPCR analyses demonstrated that T. rangeli is eliminated from the skin after 7 days of infection despite being still consistently found on circulating blood and secondary lymphoid tissues for up to 30 days post-infection. Interestingly, significant numbers of parasites were found in the spleen and mesenteric lymph nodes of infected mice during different periods of infection and steady basal numbers of flagellates are maintained in the host′s bloodstream, which might behave as a transmission source to insect vectors. The presence of parasites in the spleen was confirmed by fluorescent photomicrography of free and cell-associated T. rangeli forms. Altogether our results suggest that this organ could possibly behave as a T. rangeli maintenance hotspot in vertebrates.
Rapid and robust patterns of spontaneous locomotor deficits in mouse models of Huntington’s disease
Authors: Heikkinen Taneli , Bragge Timo , Bhattarai Niina , Parkkari Teija , Puoliväli Jukka , Kontkanen Outi , Sweeney Patrick , Park Larry C. , Munoz-Sanjuan Ignacio
Published: December 2020

Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by severe disruption of cognitive and motor functions, including changes in posture and gait. A number of HD mouse models have been engineered that display behavioral and neuropathological features of the disease, but gait alterations in these models are poorly characterized. Sensitive high-throughput tests of fine motor function and gait in mice might be informative in evaluating disease-modifying interventions. Here, we describe a hypothesis-free workflow that determines progressively changing locomotor patterns across 79 parameters in the R6/2 and Q175 mouse models of HD. R6/2 mice (120 CAG repeats) showed motor disturbances as early as at 4 weeks of age. Similar disturbances were observed in homozygous and heterozygous Q175 KI mice at 3 and 6 months of age, respectively. Interestingly, only the R6/2 mice developed forelimb ataxia. The principal components of the behavioral phenotypes produced two phenotypic scores of progressive postural instability based on kinematic parameters and trajectory waveform data, which were shared by both HD models. This approach adds to the available HD mouse model research toolbox and has a potential to facilitate the development of therapeutics for HD and other debilitating movement disorders with high unmet medical need.
Directions in abusive language training data, a systematic review: Garbage in, garbage out
Authors: Vidgen Bertie , Derczynski Leon
Published: December 2020

Data-driven and machine learning based approaches for detecting, categorising and measuring abusive content such as hate speech and harassment have gained traction due to their scalability, robustness and increasingly high performance. Making effective detection systems for abusive content relies on having the right training datasets, reflecting a widely accepted mantra in computer science: Garbage In, Garbage Out. However, creating training datasets which are large, varied, theoretically-informed and that minimize biases is difficult, laborious and requires deep expertise. This paper systematically reviews 63 publicly available training datasets which have been created to train abusive language classifiers. It also reports on creation of a dedicated website for cataloguing abusive language datahatespeechdata.com. We discuss the challenges and opportunities of open science in this field, and argue that although more dataset sharing would bring many benefits it also poses social and ethical risks which need careful consideration. Finally, we provide evidence-based recommendations for practitioners creating new abusive content training datasets.
Risk factors associated with weight gain after kidney transplantation: A cohort study
Authors: Forte Cristina Carra , Pedrollo Elis Forcellini , Nicoletto Bruna Bellincanta , Lopes Jéssica Blatt , Manfro Roberto Ceratti , Souza Gabriela Corrêa , Leitão Cristiane Bauermann
Published: December 2020

Background

Renal transplantation is the best modality of renal replacement therapy for patients with end-stage renal disease. However, it is associated with weight gain and metabolic abnormalities, which adversely impact transplant outcomes.

Objective

The objective of this study was to identify the risk factors of one-year weight gain after renal transplantation.

Methods

A retrospective cohort study was conducted with 374 patients that underwent kidney transplantation between January 2006 and July 2013. Clinical and laboratory variables were collected from electronic records, and the outcome of interest was weight gain during the first year after renal transplantation. The data were reported as mean ± standard deviation, median (interquartile range) or number of subjects (%). The association between variables were assessed via chi-square test and ANOVA. For analysis of risk factors related to the outcomes of interest, multivariable logistic regression models were used.

Results

There were 181 (48.4%) female patients, 334 (89.3%) with white ethnicity and the mean age was 44.4 ± 12.8 years. The mean BMI pre-transplant was 24.7 ± 4.1 kg/m2, and 35 (9.9%) patients were classified as obese; 119 (33.6%) as overweight; 187 (52.8%) as normal weight; and 13 (3.7%) as malnourished. After one year of follow-up, the mean BMI was 26.2 ± 5.0 kg/m2, and 61 (17.3%) patients were classified as obese; 133 (37.8%) as overweight; 148 (42.0%) as normal weight; and 10 (2.8%) as malnourished. Weight gain was observed in 72.7% patients, and the average increase was 7.12 ± 5.9 kg. The female gender, lower pre-transplant body weight, lower number of hospitalizations, and a kidney received from a living donor were associated with weight gain by more than 5% in the first year post-transplant.

Conclusion

Female gender and lower pre-transplant body weight were independently associated with weight gain by more than 5% in the first year after kidney transplantation; lower rates of hospitalization and donation from living donors were also risk factors for this outcome.
Correlation analysis of the proportion of monocytic myeloid-derived suppressor cells in colorectal cancer patients
Authors: Shirasuna Kenna , Ito Masayuki , Matsuda Takashi , Enomoto Tsuyoshi , Ohara Yusuke , Yamamoto Masayoshi , Nishijima Satomi , Ohkohchi Nobuhiro , Kuromitsu Sadao
Published: December 2020

Monocytic myeloid-derived suppressor cells (mMDSCs) are a class of immunosuppressive immune cells with prognostic value in many solid tumors. It is reported that the proportion of mMDSCs in the peripheral blood can be a predictive marker for response to cancer immunotherapy. In this study, we performed a correlation analysis of the proportion of mMDSCs in freshly-drawn peripheral blood, levels of plasma proteins, and demographic factors in colorectal cancer (CRC) patients, to find factors that could be used to predict mMDSC proportions. Freshly-drawn mMDSCs were measured using flow cytometry on peripheral blood mononuclear cells (PBMCs) from healthy donors (n = 24) and CRC patients (n = 78). The plasma concentrations of 29 different cytokines, chemokines, growth factors, and enzymes were measured using a multiplex assay or enzyme-linked immunosorbent assay. Correlation analysis to find mMDSC-associated factors was conducted using univariate and multivariate models. In univariate correlation analysis, there were no plasma proteins that were associated with mMDSC proportions in CRC patients. In multivariate analysis, considering all variables including age, sex, and plasma proteins, levels of inducible nitric acid synthase (iNOS) (p = 0.013) and platelet-derived growth factor (PDGF)-BB (p = 0.035) were associated with mMDSC proportion in PBMCs (mMDSC proportion [%] = 0.2929 − 0.2389 * PDGF-BB + 0.3582 * iNOS) (p < 0.005, r = 0.32). Measuring the plasma concentrations of iNOS and PDGF-BB may be useful in predicting the proportion of mMDSCs in CRC patients’ peripheral blood. Further research is required to establish and validate these predictive factors.

Data registration

Patient data were registered in an anonymization system at Tsukuba Clinical Research & Development Organization (T-CReDO).
Electromyographic evidence of reduced emotion mimicry in individuals with a history of non-suicidal self-injury
Authors: Ziebell Laura , Collin Charles , Mazalu Monica , Rainville Stéphane , Weippert Madyson , Skolov Misha
Published: December 2020

Engaging in facial emotion mimicry during social interactions encourages empathy and functions as a catalyst for interpersonal bonding. Decreased reflexive mirroring of facial expressions has been observed in individuals with different non-psychotic disorders, relative to healthy controls. Given reports of interpersonal relationship difficulties experienced by those who engage in non-suicidal self-injury (NSSI), it is of interest to explore facial emotion mimicry in individuals with a history of this behaviour (HNSSI). Among other things, this will enable us to better understand their emotion regulation and social interaction challenges. Surface facial electromyography (fEMG) was used to record the reflexive facial mimicry of 30 HNSSI and 30 controls while they passively observed a series of dynamic facial stimuli showing various facial expressions of emotion. Beginning with a neutral expression, the stimuli quickly morphed to one of 6 prototypic emotional expressions (anger, fear, surprise, disgust, happiness, or sadness). Mimicry was assessed by affixing surface electrodes to facial muscles known to exhibit a high degree of electrical activity in response to positive and negative emotions: the corrugator supercilii and the zygomaticus major. HNSSI participants, relative to controls, exhibited significantly less electrical activity in the corrugator muscle in response to viewing angry stimuli, and significantly less of an expected relaxation in muscle activity in response to viewing happy stimuli. Mirroring these results, greater endorsement of social influence as a motivator for engaging in NSSI was associated with less mimicry, and greater endorsement of emotion regulation as a motivator was associated with greater incongruent muscle response when viewing happy faces. These findings lend support to the theory that social interaction difficulties in HNSSI might be related to implicit violations of expected social rules exhibited through facial mimicry nonconformity.
Borrelia burgdorferi and Borrelia miyamotoi seroprevalence in California blood donors
Authors: Brummitt Sharon I. , Kjemtrup Anne M. , Harvey Danielle J. , Petersen Jeannine M. , Sexton Christopher , Replogle Adam , Packham Andrea E. , Bloch Evan M. , Barbour Alan G. , Krause Peter J. , Green Valerie , Smith Woutrina A.
Published: December 2020

The western blacklegged tick, Ixodes pacificus, an important vector in the western United States of two zoonotic spirochetes: Borrelia burgdorferi (also called Borreliella burgdorferi), causing Lyme disease, and Borrelia miyamotoi, causing a relapsing fever-type illness. Human cases of Lyme disease are well-documented in California, with increased risk in the north coastal areas and western slopes of the Sierra Nevada range. Despite the established presence of B. miyamotoi in the human-biting I. pacificus tick in California, clinical cases with this spirochete have not been well studied. To assess exposure to B. burgdorferi and B. miyamotoi in California, and to address the hypothesis that B. miyamotoi exposure in humans is similar in geographic range to B. burgdorferi, 1,700 blood donor sera from California were tested for antibodies to both pathogens. Sampling was from high endemic and low endemic counties for Lyme disease in California. All sera were screened using the C6 ELISA. All C6 positive and equivocal samples and nine randomly chosen C6 negative samples were further analyzed for B. burgdorferi antibody using IgG western blot and a modified two ELISA test system and for B. miyamotoi antibody using the GlpQ ELISA and B. miyamotoi whole cell sonicate western blot. Of the 1,700 samples tested in series, eight tested positive for antibodies to B. burgdorferi (0.47%, Exact 95% CI: 0.20, 0.93) and two tested positive for antibodies to B. miyamotoi (0.12%, Exact 95% CI: 0.01, 0.42). There was no statistically significant difference in seroprevalence for either pathogen between high and low Lyme disease endemic counties. Our results confirm a low frequency of Lyme disease and an even lower frequency of B. miyamotoi exposure among adult blood donors in California; however, our findings reinforce public health messaging that there is risk of infection by these emerging diseases in the state.
Participation in community-based health care interventions (CBHIs) and its association with hypertension awareness, control and treatment in Indonesia
Authors: Sujarwoto Sujarwoto , Maharani Asri
Published: December 2020

Background

Little attention has been paid to whether CBHIs improve awareness, treatment and control of hypertension in the contexts of low- and middle- income countries (LMICs). This study therefore aims to examine participation in CBHIs for non-communicable diseases (NCDs) and its association with awareness, treatment, and control of hypertension among Indonesians.

Methods

This study used data from the 2014 Indonesia Family Life Survey (IFLS), drawn from 30,351 respondents aged 18 years and older. Participation in CBHIs was measured by respondents’ participation in CBHIs for NCDs (Posbindu PTM and Posbindu Lansia) during the 12 months prior to the survey. Logistic regressions were used to identify the relationships between participation in CBHIs for NCDs and awareness, treatment, and control of blood pressure among respondents with hypertension.

Results

The age-adjusted prevalence of hypertension was 31.2% and 29.2% in urban and rural areas, respectively. The overall age-adjusted prevalence was 30.2%. Approximately 41.8% of respondents with hypertension were aware of their condition, and only 6.6% of respondents were receiving treatment. Participation in CBHIs for NCDs was associated with 50% higher odds of being aware and 118% higher odds of receiving treatment among adults with hypertension. There was no significant association between participation in CBHIs for NCDs and controlled hypertension.

Conclusion

Our data emphasise the importance of CBHIs for NCDs to improve the awareness and treatment of hypertension in the Indonesian population.
Determinants of cigarette/bidi smoking among youth male in rural Mymensingh of Bangladesh: A cross-sectional study
Authors: Rahman K. M. Mustafizur , Tareque Md. Ismail
Published: December 2020

Background

Smoking cigarette/bidi, is a serious health threat, causes preventable premature morbidity and mortality. Higher prevalence of smoking among the youth hampers a country’s development, as the youth are the main drivers of socio-economic development. An effective understanding of factors associated with youth smoking is precious to prevent youth smoking. This study aims to identify the determinants of smoking cigarette/bidi among the youth male of the rural areas of Mymensingh district in Bangladesh.

Methods

The primary data from the project “Knowledge, awareness and practices among youth smokers in Trishal Upazila under Mymensingh district: A micro-survey study”, funded by the Research and Extension Center, Jatiya Kabi Kazi Nazrul Islam University, Bangladesh was utilized in the current study. The data consists of 385 youth males aged 15–24 years who were interviewed face-to-face from the rural areas of Mymensingh district in Bangladesh. Univariate distribution, chi-square tests, and binary logistic regression model were employed to identify the factors associated with smoking cigarette/bidi among the youth male.

Results

The prevalence of smoking cigarette/bidi among the youth male is 40.3% [95% CI: 35.0%-45.0%]. Age, occupation, monthly income, family’s monthly income, cigarette/bidi smoking status of father, brother and close friends, and knowledge about harmfulness of smoking are revealed as the determinants of cigarette/bidi smoking. For instance, the odds of being smoker increases with the increase in age (Odds ratio [OR]: 1.33 [1.17–1.51]). Business owner is less likely (OR: 0.15 [0.03–0.68]) to smoke than the day labourer. Having smoker fathers (OR: 2.51 [1.39–4.53]), smoker brothers (OR: 2.88 [1.39–5.96]), smoker friends (OR: 9.85 [5.85–1.27]) are significantly associated with smoking cigarette/bidi.

Conclusion

As the first study, it provides the determinants of cigarette/bidi smoking among youth male of the rural areas of Mymensingh district in Bangladesh. Relevant authorities are suggested to consider the study’s findings and recommendations to revise the existing smoking policies so that smoking among youth can be prevented for future development of the country.
In vitro and in vivo characterization of Recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia
Authors: Gonçalves Diogo , Rignol Guylène , Dellugat Pierre , Hartmann Guido , Sarrazy Garcia Stephanie , Stavenhagen Jeffrey , Santarelli Luca , Gouze Elvire , Czech Christian
Published: December 2020

Achondroplasia is a rare genetic disorder caused by mutations in the Fibroblast Growth Factor receptor 3 (FGFR3). These mutations lead to aberrant increase of inhibitory signaling in proliferating chondrocytes at the growth plate. Recifercept is a potential treatment for this disease using a decoy approach to sequester FGFR3 ligands subsequently normalizing activation of the mutated FGFR3 receptor. Recifercept binds to FGF isoformsin vitroand in cellular model systems and reduces FGFR3 signaling. In addition, in a transgenic mouse model of achondroplasia, Recifercept restores reduced body weight and long bone growth in these mice. These data suggest that Recifercept treatment could lead to clinical benefits in children treated with this molecule.
Non-invasive myocardial work is reduced during transient acute coronary occlusion
Authors: Sabatino Jolanda , De Rosa Salvatore , Leo Isabella , Spaccarotella Carmen , Mongiardo Annalisa , Polimeni Alberto , Sorrentino Sabato , Di Salvo Giovanni , Indolfi Ciro
Published: December 2020

Background

During ischemia a close relationship exists between sub-endocardial blood flow and myocardial function. Strain parameters can capture an impairment of regional longitudinal function but are load dependent. Recently, a novel non-invasive method to calculate Myocardial Work (MW) showed a strong correlation with invasive work measurements.

Our aim was to investigate the ability of non-invasive MW indices to identify the ischaemic risk area during transient acute coronary occlusion (TACO).

Methods and results

The study population comprises 50 individuals with critical coronary stenosis (CCS). Echocardiography recordings were obtained before coronary angiography, during TACO and after revascularization to measure global longitudinal strain (GLS), Myocardial Work Index (MWI), Myocardial Constructive Work (MCW), Myocardial Wasted work (MWW), Myocardial work efficiency (MWE).

Compared to baseline, we found a significant reduction of GLS (p = 0.005), MWI, MCW and MWE (p<0.001) during TACO.

Conclusions

The non-invasive measurement of MW parameters is a sensitive and early marker of myocardial ischemia during TACO.
A human-based assisted reproduction protocol for the menstruating spiny mouse, Acomys cahirinus
Authors: McKenna Jarrod , Bellofiore Nadia , Catt Sally , Pangestu Mulyoto , Temple-Smith Peter
Published: December 2020

The Egyptian or Common spiny mouse (A. cahirinus) is the first rodent species to show human-like menstruation and spontaneous decidualisation. We consider from these, and its other, human-like characteristics that this species will be a more useful and appropriate small animal model for human reproductive studies. Based on this, there is a need to develop specific laboratory-based assisted reproduction protocols including superovulation, in-vitro fertilisation, embryo cryopreservation and transfer to expand and make this model more relevant. Because standard rodent superovulation has not been successful in the spiny mouse, we have selected to test a human protocol. Female spiny mice will receive a subcutaneous GnRH agonist implant and be allowed to recover. Menstrual cycle lengths will then be allowed to stabilize prior to ovarian stimulation. After recovery, females will be injected IP once a day for 4 days with a FSH analogue, to induce follicular growth, and on day 5 will be injected IP with a hCG analogue to trigger ovulation. Females will either be culled 36hrs after trigger to collect oocytes or immediately paired with a stud male and two cell embryos collected 48hrs later. Mature oocytes will be inseminated using fresh spiny mouse spermatozoa and all in-vitro grown and in-vivo collected two cell embryos will be cryopreserved using methods developed in a close spiny mouse relative, the Mongolian gerbil. For embryo transfer, vitrified embryos will be rapidly warmed and non-surgically transferred to surrogate mice. Surrogates will be monitored until pregnancy is apparent (roughly 30 days) and then left undisturbed until birth, 38–40 days after transfer. By successfully developing robust assisted reproduction protocols in A. cahirinus we will be able to use this rodent as a more effective model for human reproduction.
Rural-to-urban migration, discrimination experience, and health in China: Evidence from propensity score analysis
Authors: Deng Zihong , Law Yik Wa
Published: December 2020

This research examines how rural-to-urban migration influences health through discrimination experience in China after considering migration selection bias. We conducted propensity score matching (PSM) to obtain a matched group of rural residents and rural-to-urban migrants with a similar probability of migrating from rural to urban areas using data from the 2014 China Family Panel Studies (CFPS). Regression and mediation analyses were performed after PSM. The results of regression analysis after PSM indicated that rural-to-urban migrants reported more discrimination experience than rural residents, and those of mediation analysis revealed discrimination experience to exert negative indirect effects on the associations between rural-to-urban migration and three measures of health: self-reported health, psychological distress, and physical discomfort. Sensitivity analysis using different calipers yielded similar results. Relevant policies and practices are required to respond to the unfair treatment and discrimination experienced by this migrant population.
Social and financial efficiency: Institutional characteristics of the partner organizations of Pakistan Poverty Alleviation Fund
Authors: Ali Zulfiqar , Ullah Ikram , Nazir Naila , Asif Muhammad , Azeem Muhammad
Published: December 2020

Efficiency analysis of the Partner Organizations can benefit all the microfinance sector's key stakeholders to benchmark the current scene and formulate optimal policy agenda. This study seeks to measure the partner organizations of the Pakistan Poverty Alleviation Fund's social and financial efficiency and to identify causes and sources of their inefficiencies. A non-parametric technique known as Data Envelopment Analysis is applied to investigate the Partner Organizations' efficiency throughout 2005–2015. The required data was obtained from the database of the Mix-Market and Pakistan Microfinance Network. The social and financial efficiency was estimated assuming Constant Return to Scale, Variable Return to Scale, and with respect to the Operational Scale of the Partner Organizations. Results revealed that the partner organizations are more scale efficient (median = 75%) than pure technically efficient (median = 55%). Further, graphical representations show a decreasing linear trend and negative serial correlation in the percentage of efficient partner organizations. The model fit results show that institutional characteristics that influence partner organizations' efficiencies significantly include their age, Operational Self-Sufficiency, personnel, loan officers, assets and debt. Finally, the diagnostic tests for endogeneity, heteroskedasticity, heterogeneity, and cross-sectional dependence were performed.
Tracing the active genetic diversity of Microcystis and Microcystis phage through a temporal survey of Taihu
Authors: Pound Helena L. , Wilhelm Steven W.
Published: December 2020

Harmful algal blooms are commonly thought to be dominated by a single genus, but they are not homogenous communities. Current approaches, both molecular and culture-based, often overlook fine-scale variations in community composition that can influence bloom dynamics. We combined homology-based searches (BLASTX) and phylogenetics to distinguish and quantifyMicrocystishost and phage members across a summer season during a 2014Microcystis-dominated bloom that occurred in Lake Tai (Taihu), China. We found 47 different genotypes of theMicrocystis-specific DNA-dependent RNA polymerase (rpoB), which included several morphospecies.Microcystis flos-aquaeandMicrocystis wesenbergiiaccounted for ~86% of totalMicrocystistranscripts, while the more commonly studiedMicrocystis aeruginosaonly accounted for ~7%.Microcystisgenotypes were classified into three temporal groups according to their expression patterns across the course of the bloom: early, constant and late. AllMicrocystismorphospecies were present in each group, indicating that expression patterns were likely dictated by competition driven by environmental factors, not phylogeny. We identified three primaryMicrocystis-infecting phages based on the viral terminase, including a novelSiphoviridaephage that may be capable of lysogeny. Within our dataset,Myoviridaephages consistent with those infectingMicrocystisin a lytic manner were positively correlated to the early host genotypes, while theSiphoviridaephages were positively correlated to the late host genotypes, when theMyoviridaephages express putative genetic markers for lysogeny. The expression of genes in the microcystin-encodingmcycassette was estimated usingmcyA, which revealed 24Microcystis-specific genotypes that were negatively correlated to the early host genotypes. Of all environmental factors measured, pH best described the temporal shift in theMicrocystiscommunity genotypic composition, promoting hypotheses regarding carbon concentration mechanisms and oxidative stress. Our work expounds on the complexity of HAB events, using a well-studied dataset to highlight the need for increased resolution of community dynamics.
Factors associated with psychological distress during the coronavirus disease 2019 (COVID-19) pandemic on the predominantly general population: A systematic review and meta-analysis
Authors: Wang Yeli , Kala Monica Palanichamy , Jafar Tazeen H.
Published: December 2020

Background

The Coronavirus Disease 2019 (COVID-19) outbreak has escalated the burden of psychological distress. We aimed to evaluate factors associated with psychological distress among the predominantly general population during the COVID-19 pandemic.

Methods

We searched PubMed, EMBASE, Scopus, Cochrane Library, PsycINFO, and World Health Organization COVID-19 databases (Dec 2019–15 July 2020). We included cross-sectional studies that reported factors associated with psychological distress during the COVID-19 pandemic. Primary outcomes were self-reported symptoms of anxiety and depression. Random-effects models were used to pool odds ratios (OR) and 95% confidence intervals (CI). The protocol was registered in PROSPERO (#CRD42020186735).

Findings

We included 68 studies comprising 288,830 participants from 19 countries. The prevalence of anxiety and depression was 33% (95% CI: 28%-39%) and 30% (26%-36%). Women versus men (OR: 1.48 [95% CI: 1.29–1.71; I2 = 90.8%]), younger versus older (< versus ≥35 years) adults (1.20 [1.13–1.26]; I2 = 91.7%), living in rural versus urban areas (1.13 [1.00–1.29]; I2 = 82.9%), lower versus higher socioeconomic status (e.g. lower versus higher income: 1.45 [1.24–1.69; I2 = 82.3%]) were associated with higher anxiety odds. These factors (except for residential area) were also associated with higher depression odds. Furthermore, higher COVID-19 infection risk (suspected/confirmed cases, living in hard-hit areas, having pre-existing physical or mental conditions) and longer media exposure were associated with higher odds of anxiety and depression.

Interpretation

One in three adults in the predominantly general population have COVID-19 related psychological distress. Concerted efforts are urgently needed for interventions in high-risk populations to reduce urban-rural, socioeconomic and gender disparities in COVID-19 related psychological distress.
Helicobacter pylori diversification during chronic infection within a single host generates sub-populations with distinct phenotypes
Authors: Jackson Laura K. , Potter Barney , Schneider Sean , Fitzgibbon Matthew , Blair Kris , Farah Hajirah , Krishna Uma , Bedford Trevor , Peek Richard M. , Salama Nina R.
Published: December 2020

Helicobacter pylorichronically infects the stomach of approximately half of the world’s population. Manifestation of clinical diseases associated withH.pyloriinfection, including cancer, is driven by strain properties and host responses; and as chronic infection persists, both are subject to change. Previous studies have documented frequent and extensive within-host bacterial genetic variation. To define how within-host diversity contributes to phenotypes related toH.pyloripathogenesis, this project leverages a collection of 39 clinical isolates acquired prospectively from a single subject at two time points and from multiple gastric sites. During the six years separating collection of these isolates, this individual, initially harboring a duodenal ulcer, progressed to gastric atrophy and concomitant loss of acid secretion. Whole genome sequence analysis identified 1,767 unique single nucleotide polymorphisms (SNPs) across isolates and a nucleotide substitution rate of 1.3x10-4substitutions/site/year. Gene ontology analysis identified cell envelope genes among the genes with excess accumulation of nonsynonymous SNPs (nSNPs). A maximum likelihood tree based on genetic similarity clusters isolates from each time point separately. Within time points, there is segregation of subgroups with phenotypic differences in bacterial morphology, ability to induce inflammatory cytokines, and mouse colonization. Higher inflammatory cytokine induction in recent isolates maps to shared polymorphisms in the Cag PAI protein, CagY, while rod morphology in a subgroup of recent isolates mapped to eight mutations in three distinct helical cell shape determining (csd) genes. The presence of subgroups with unique genetic and phenotypic properties suggest complex selective forces and multiple niches within the stomach during chronic infection.
The latency-associated transcript locus of herpes simplex virus 1 is a virulence determinant in human skin
Authors: Vanni Emilia A. H. , Foley Joseph W. , Davison Andrew J. , Sommer Marvin , Liu Dongmei , Sung Phillip , Moffat Jennifer , Zerboni Leigh , Arvin Ann M.
Published: December 2020

Herpes simplex virus 1 (HSV-1) infects skin and mucosal epithelial cells and then travels along axons to establish latency in the neurones of sensory ganglia. Although viral gene expression is restricted during latency, the latency-associated transcript (LAT) locus encodes many RNAs, including a 2 kb intron known as the hallmark of HSV-1 latency. Here, we studied HSV-1 infection and the role of the LAT locus in human skin xenografts in vivo and in cultured explants. We sequenced the genomes of our stock of HSV-1 strain 17syn+ and seven derived viruses and found nonsynonymous mutations in many viral proteins that had no impact on skin infection. In contrast, deletions in the LAT locus severely impaired HSV-1 replication and lesion formation in skin. However, skin replication was not affected by impaired intron splicing. Moreover, although the LAT locus has been implicated in regulating gene expression in neurones, we observed only small changes in transcript levels that were unrelated to the growth defect in skin, suggesting that its functions in skin may be different from those in neurones. Thus, although the LAT locus was previously thought to be dispensable for lytic infection, we show that it is a determinant of HSV-1 virulence during lytic infection of human skin.
Signal peptide of HIV-1 envelope modulates glycosylation impacting exposure of V1V2 and other epitopes
Authors: Upadhyay Chitra , Feyznezhad Roya , Cao Liwei , Chan Kun-Wei , Liu Kevin , Yang Weiming , Zhang Hui , Yolitz Jason , Arthos James , Nadas Arthur , Kong Xiang-Peng , Zolla-Pazner Susan , Hioe Catarina E.
Published: December 2020

HIV-1 envelope (Env) is a trimer of gp120-gp41 heterodimers, synthesized from a precursor gp160 that contains an ER-targeting signal peptide (SP) at its amino-terminus. Each trimer is swathed by ~90 N-linked glycans, comprising complex-type and oligomannose-type glycans, which play an important role in determining virus sensitivity to neutralizing antibodies. We previously examined the effects of single point SP mutations on Env properties and functions. Here, we aimed to understand the impact of the SP diversity on glycosylation of virus-derived Env and virus neutralization by swapping SPs. Analyses of site-specific glycans revealed that SP swapping altered Env glycan content and occupancy on multiple N-linked glycosites, including conserved N156 and N160 glycans in the V1V2 region at the Env trimer apex and N88 at the trimer base. Virus neutralization was also affected, especially by antibodies against V1V2, V3, and gp41. Likewise, SP swaps affected the recognition of soluble and cell-associated Env by antibodies targeting distinct V1V2 configurations, V3 crown, and gp41 epitopes. These data highlight the contribution of SP sequence diversity in shaping the Env glycan content and its impact on the configuration and accessibility of V1V2 and other Env epitopes.
The nature of feedback in higher education studio-based piano learning and teaching with the use of digital technology1
Authors: Hamond Luciana , Himonides Evangelos , Welch Graham
Published: December 2020

The aim of the current research was to investigate the nature of feedback when a digital technology system was introduced in the higher education (HE) piano studio alongside three teacher and student pairs in Brazil. Data were collected by using video-recorded observations of lessons, participant interviews, and also data related to the use of a specific technology. A thematic analysis of the resultant data suggests that participants used verbal and non-verbal feedback in three areas of lesson focus: music (score), performance (e.g. dynamics, articulation), and technology (Musical Instrument Digital Interface [MIDI] parameters). The application of technology seems to allow the focus of the lesson to become clearer, making students more aware of their performances and their learning processes. Data suggest that the engagement with technology varied across the three observed cases. There seems to be a valuable use for technology-mediated feedback; this could, in turn, optimize more traditional pedagogical approaches in HE piano learning and teaching, and also enrich private practice.
Teaching Music Online in Higher Education: 2020 conference report
Authors: Merrick Brad , Johnson Carol
Published: December 2020

Faced with the state of emergency restrictions due to the global COVID-19 pandemic, the 2020 Teaching Music Online in Higher Education conference was adaptively modified to exist as a synchronous, online event. Embracing the opportunity to model online music pedagogy in its online format, organizers transformed the conference to utilize live-streaming, video recordings and other online active learning strategies. A total of 143 tertiary music instructors and graduate students from 66 institutions located around the world took part in the conference at a time of unprecedented restriction on face-to-face learning and travel restrictions. This report is both important and timely, as it provides insights into components that were found to be both necessary and fundamental to the success of the event for music researchers, teachers and other delegates in attendance. Key areas related to organization, communication, structure, protocols and activities were explored through learning analytics and a conference evaluation. Strategies and recommendations are included to assist others who wish to create and present an online conference that exemplifies online pedagogy principles.
Neuropsychological Syndrome and long term effects of Exposure to Organophosphate Pesticides in Humans
Authors: Zameer Dr.Maida , Siddique Dr. Sunbal , Baig Dr.Maria
Published: December 2020

Organophosphorous compounds, the anticholinesterases, produce significant morbidity and mortality in Pakistan. Neuropsychological assessment was traditionally carried out to assess the extent of impairment to a particular skill and to attempt to determine the area of the brain which may have been damaged following brain injury or neurological illness. With the advent of neuroimaging techniques, location of space-occupying lesions can now be more accurately determined through this method, so the focus has now moved on to the assessment of cognition and behaviour, including examining the effects of any brain injury or neuropathological process that a person may have experienced.