bluuebunny/crossref_metadata_2025 huggingface dataset:
Who is Reached by HIV Self-Testing? Individual Factors Associated With Self-Testing Within a Community-Based Program in Rural Malawi
Authors: Indravudh Pitchaya P. , Hensen Bernadette , Nzawa Rebecca , Chilongosi Richard , Nyirenda Rose , Johnson Cheryl C. , Hatzold Karin , Fielding Katherine , Corbett Elizabeth L. , Neuman Melissa
Published: June 2020

Introduction:

HIV self-testing (HIVST) is an alternative strategy for reaching population subgroups underserved by available HIV testing services. We assessed individual factors associated with ever HIVST within a community-based program.

Setting:

Malawi.

Methods:

We conducted secondary analysis of an end line survey administered under a cluster-randomized trial of community-based distribution of HIVST kits. We estimated prevalence differences and prevalence ratios (PRs) stratified by sex for the outcome: self-reported ever HIVST.

Results:

Prevalence of ever HIVST was 45.0% (475/1055) among men and 40.1% (584/1456) among women. Age was associated with ever HIVST in both men and women, with evidence of a strong declining trend across categories of age. Compared with adults aged 25–39 years, HIVST was lowest among adults aged 40 years and older for both men [34.4%, 121/352; PR 0.74, 95% confidence interval (CI): 0.62 to 0.88] and women (30.0%, 136/454; PR 0.71, 95% CI: 0.6 to 0.84). Women who were married, had children, had higher levels of education, or were wealthier were more likely to self-test. Men who had condomless sex in the past 3 months (47.9%, 279/582) reported a higher HIVST prevalence compared with men who did not have recent condomless sex (43.1%, 94/218; adjusted PR 1.37, 95% CI: 1.06 to 1.76). Among men and women, the level of previous exposure to HIV testing and household HIVST uptake was associated with HIVST.

Conclusions:

Community-based HIVST reached men, younger age groups, and some at-risk individuals. HIVST was lowest among older adults and individuals with less previous exposure to HIV testing, suggesting the presence of ongoing barriers to HIV testing.
Lung Ultrasound for the Diagnosis of Neonatal Respiratory Distress Syndrome
Authors: Wu Jiangfeng , Wang Yunlai , Zhao Anli , Wang Zhengping
Published: June 2020

Chest radiography is the primary imaging modality used for the assessment of neonatal respiratory distress syndrome (NRDS) in newborns. However, excessively exposing a growing neonate to harmful ionizing radiation may have long-term consequences. Some studies have shown that lung ultrasound (LUS) is helpful in the diagnosis of NRDS. A comprehensive search was carried out using PubMed, Embase, and the Cochrane Library to identify studies in which newborns with clinically suspected NRDS were assessed by LUS. Two investigators independently screened the literature and extracted the data. Any discrepancies were resolved via discussion with the senior author. Study quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies 2 tool, and pooled sensitivity and specificity of various LUS findings for diagnosing NRDS were determined. Summary receiver operating characteristic curve was used to assess the overall performance of LUS. Ten studies with a total of 887 neonates were included in this meta-analysis. There was significant heterogeneity across the included studies. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio for the diagnosis of NRDS using LUS were 0.92 (95% confidence interval [CI], 0.89–0.94), 0.95 (95% CI, 0.93–0.97), 20.23 (95% CI, 8.54–47.92), 0.07 (95% CI, 0.03–0.14), and 455.30 (95% CI, 153.01–1354.79), respectively. Furthermore, the summary receiver operating characteristic area under the curve was calculated to be 0.9888. The main LUS characteristics of NRDS include bilateral white lung, pleural line abnormalities, and lung consolidation. In summary, LUS is a highly valuable diagnostic technology that complements chest radiography in the diagnosis and follow-up monitoring of NRDS.
Two-stage Reconstruction Using a Free Jejunum/Ileum Flap After Total Esophagectomy
Authors: Iida Takuya , Yoshimatsu Hidehiko , Seto Yasuyuki , Mori Kazuhiko , Okazaki Mutsumi
Published: June 2020

Background

Reconstruction after esophagectomy is conventionally performed with a gastric conduit. However, in cases where a gastric conduit is unavailable, reconstructive procedures vary in terms of flap type, operative timing, and conduit route. Single-stage surgery is associated with a long operation time and high surgical stress, resulting in perioperative mortality. Recent advances in reconstructive microsurgery have made free intestinal flap transfer safe and reliable. Therefore, to overcome the shortcomings with previous methods, we performed 2-stage surgery involving free jejunum/ileum transfer for reconstruction after esophagectomy.

Patients and Methods

From 2010 to 2018, 42 free jejunum/ileum flaps were transferred for reconstruction after esophagectomy in 41 patients. The diagnosis was esophageal cancer in 38 patients. All operations were performed in 2 stages. In most cases, total esophagectomy was performed in the first operation. The cervical stump of the esophagus was sutured to the cervical skin, creating an esophagostomy in the left neck. About 4 to 7 weeks after the first operation, the second operation was performed. The free jejunum/ileum flap was transferred through the subcutaneous route. Microvascular anastomosis was performed with the internal mammary artery and internal mammary vein, transverse cervical artery, internal and external jugular veins (internal jugular vein and EJV, respectively), and cephalic vein. The mean follow-up duration was 20 months.

Results

Free jejunum/ileum transfer was performed as the first operation in 4 cases and as the second operation in 38 cases. A free jejunal flap was used in 36 cases and free ileal flap was used in 6 cases. The recipient arteries were the internal mammary artery in 38 cases and transverse cervical artery in 4 cases. The recipient veins were the internal mammary vein in 15 cases, cephalic vein in 13 cases, EJV in 10 cases, and internal jugular vein in 10 cases. The flaps survived in all cases, except 1 case (41/42, 97.6%). The complications were anastomotic leakage of the flap in 9 cases, respiratory complications in 10 cases, and ileus in 2 cases. Perioperative mortality was not noted.

Conclusions

Two-stage surgery using free jejunum/ileum flap transfer is a safe and reliable option for esophageal reconstruction in cases where gastric pull-up is unavailable.
Long Term Speech Outcomes Following Midface Advancement in Syndromic Craniosynostosis
Authors: Zimmerman Carrie E. , Sun James , Wes Ari M. , Vu Giap H. , Kalmar Christopher L. , Humphries Laura S. , Bartlett Scott P. , Cohen Marilyn A. , Swanson Jordan W. , Taylor Jesse A.
Published: June 2020

Midface advancement by distraction osteogenesis (DO) is commonly performed in patients with craniosynostosis for indications including midface hypoplasia, exorbitism, obstructive sleep apnea, class III malocclusion, and overall aesthetic facial deficiency.
1
There is evidence to suggest that maxillary LeFort I advancement increases the risk of velopharyngeal dysfunction in the cleft palate population,
2,3
yet few studies have investigated changes in speech following LeFort III or monobloc midface advancement in patients with syndromic craniosynostosis. The purpose of this study was to examine the effect of midface DO on speech as indicated by the Pittsburgh Weighted Speech Score in patients with Apert, Crouzon, and Pfeiffer Syndrome. Among 73 midface advancement cases performed during the study period, 19 cases met inclusion criteria. Overall, the highest post-advancement Pittsburgh Weighted Speech Score (PWSS) was significantly higher than the pre-advancement PWSS (0.52 versus 2.42, P = 0.01), indicating an acute worsening of VPI post-advancement. Specifically, the PWSS components nasal emission and nasality were significantly higher post-advancement than pre-advancement (nasal emission: 1.16 versus 0.21, P = 0.02) (nasality: 0.68 versus 0.05, P = 0.04). However, there was no significant difference between pre-advancement PWSS and the latest post-advancement PWSS (P = 0.31). Midface distraction is associated with an acute worsening of VPI post-operatively that is followed by improvement, and often resolution over time. Future work with additional patient accrual is needed to determine the effect of different advancement procedures and syndromes on VPI rates and profundity.
Trauma in Iraq's Wars: Assessment and Management of Craniofacial Injury
Authors: Al Bayati Mahmood J. , Samaha Georges J. , Al Bayati Ahmed J. , Kummoona Raja , Habal Mutaz B. , Thaller Seth R.
Published: June 2020

As the most prominent portion of the human body, the face embraces a multifaceted responsibility for functionality and survival while contributing to identity and self-image. Inopportunely, due to its distinctive anatomical location, the face as a unit is highly suspectable to trauma, particularly in warfare. As a result, facial injury creates a physical and psychological trauma that needs to be addressed immediately. In the following article, a detailed literature review was conducted to examine the interplay between facial injuries throughout multiple wars in Iraq and their management. The authors found a significant increase in facial injuries due to shell fragments corresponding with modern advances in warfare targeting mass casualties. The capacity to manage the magnitude and level of trauma observed in Iraq requires a substantial amount of resources and a systematic approach that unfortunately is unattainable in a country that is still struggling to rebuild after decades of oppression and war. Due to the circumstances, surgeons have to rely on training and experience to provide the best care for their patients and it is imperative that we continue to train our surgeons to rely on their skills and experience to ensure a high level of care with limited resources and lack of technology.
Pseudomonas yangonensis sp. nov., isolated from wound samples of patients in a hospital in Myanmar
Authors: Tohya Mari , Watanabe Shin , Teramoto Kanae , Tada Tatsuya , Kuwahara-Arai Kyoko , Mya San , Zin Khwar Nyo , Kirikae Teruo , Tin Htay Htay
Published: June 2020

Strains of a Gram-negative, aerobic, rod-shaped, non-spore-forming bacterium, designated MY50T, MY63 and MY101, were isolated from wound samples of three hospitalized patients in Yangon, Myanmar. Strains MY50T, MY63 and MY101 grew at temperatures of 4–44 °C, in media containing 1.0–7.0 % (w/v) NaCl and at pH 6.0–9.5. Phylogenetic analysis based on 16S rRNA gene and whole genome sequences showed that these strains belonged to the genus

Pseudomonas

and were part of the

Pseudomonas oleovorans

group and located close to

Pseudomonas guguanensis

and

Pseudomonas mendocina

. Whole-genome comparisons, using average nucleotide identity and digital DNA–DNA hybridization analyses, confirmed that strains MY50T, MY63 and MY101 were the same strain and they were a distinct species in the

P. oleovorans

group. Results of phenotypic characterization tests demonstrated that utilization of p-hydroxy-phenylacetic acid, glycerol, l-pyroglutamic acid and quinic acid could distinguish these strains from other species of the

P. oleovorans

group. These genetic and phenotypic characteristics suggest that they should be classified as representing a novel species, under the proposed name Pseudomonas yangonensis sp. nov. The type strain is MY50T (=LMG 31602T,=JCM 33396T), with a DNA G+C content of 62.82 mol%.
Actinomarinicola tropica gen. nov. sp. nov., a new marine actinobacterium of the family Iamiaceae, isolated from South China Sea sediment environments
Authors: He Yuan-Qiu , Chen Rou-Wen , Li Cun , Shi Song-Biao , Cui Lin-Qing , Long Li-Juan , Tian Xin-Peng
Published: June 2020

A novel marine actinobacterium, strain SCSIO 58843T, was isolated from the sediment sample collected from the South China Sea. Strain SCSIO 58843T was Gram-stain-positive, aerobic and rod shaped. The whole-cell hydrolysis of amino acids contained dd-DAP, alanine, glutamic acid, glycine and aspartic acid. The main menaquinone was MK-9(H8). The major fatty acids were C17 : 1
 ω8c and C17 : 0. The major phospholipids were diphosphatidylglycerol (DPG), phosphatidylinositol (PI), phospatidylcholine (PC) and phosphatidylinositolmannoside (PIM). The G+C content of the genomic DNA was 72.5 %. Phylogenetic analysis of the 16S rRNA gene sequences showed that strain SCSIO 58843T formed a new lineage in the family

Iamiaceae

and had the highest similarity of 93.8 % with

Iamia majanohamensis

DSM 19957T. Strain SCSIO 58843T can be distinguished from these known genera in the family

Iamiaceae

by polyphasic data analyses, and represents a novel genus and novel species, for which Actinomarinicola tropica gen. nov., sp. nov is proposed with the type strain SCSIO 58843T(=KCTC 49408T=CGMCC 1.17503T).
Echinicola soli sp. nov., isolated from alkaline saline soil
Authors: Xing Ya-Ting , Xu Lian , Wang Hai-Tao , Huang Xiao-Xian , Wang Shuai , Sun Ji-Quan
Published: June 2020

Strains of

Echinicola

, thought to play vital roles in the environment for their high enzyme production capacity during decomposition of polysaccharides, are ubiquitous in hypersaline environments. A Gram-negative, non-spore forming, gliding, aerobic bacterial strain, designated LN3S3T, was isolated from alkaline saline soil sampled in Tumd Right Banner, Inner Mongolia, northern PR China. Strain LN3S3T grew at 10–40 °C (optimum, 30 °C), pH 5.0–9.0 (optimum, pH 8.0) and with 0–12.5 % NaCl (optimum, 2.0 %). A phylogenetic tree based on the 16S rRNA gene sequences showed that strain LN3S3T clustered with

Echinicola rosea

JL3085T and

Echinicola strongylocentroti

MEBiC08714T, sharing 97.0, 96.7 and <96.50 % of 16S rRNA gene sequence similarities to

E. rosea

JL3085T,

E. strongylocentroti

MEBiC08714T and all other type strains. MK-7 was the major respiratory quinone, while phosphatidylethanolamine, two unidentified phospholipids, an unidentified aminophospholipid, an unidentified lipid and two unidentified aminolipids were the major polar lipids. Its major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0 and summed feature 3 (C16 : 1
 ω7c and/or C16 : 1
 ω6c). The genome consisted of a circular 5 550 304 bp long chromosome with a DNA G+C content of 44.0 mol%. The average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA–DNA hybridization (dDDH) values of strain LN3S3T to

E. rosea

JL3085T and

E. strongylocentroti

MEBiC08714T were 82.5 and 81.5 %, 87.5 and 86.0 %, and 39.1 and 35.1 %, respectively. Based on physiological, genotypic and phylogenetic analyses, strain LN3S3T could be discriminated from its phylogenetic relatives. Echinicola soli sp. nov. is therefore proposed with strain LN3S3T (=CGMCC 1.17081T=KCTC 72458T) as the type strain.
Productive herpesvirus lytic replication in primary effusion lymphoma cells requires S-phase entry
Authors: Hollingworth Robert , Stewart Grant S. , Grand Roger J.
Published: June 2020

Gammaherpesviruses establish lifelong latent infection in B lymphocytes and are the causative agent of several B-cell malignancies and lymphoproliferative disorders. While a quiescent latent infection allows these pathogens to evade immune detection, initiation of an alternative lifecycle stage, known as lytic replication, is an essential step in the production and dissemination of infectious progeny. Although cessation of cellular proliferation is an eventual consequence of lytic induction, exactly how gammaherpesviruses manipulate the cell cycle prior to amplification of viral DNA remains under debate. Here we show that the onset of Kaposi's sarcoma-associated herpesvirus (KSHV) lytic reactivation in B cells leads to S-phase accumulation and that exit from G1 is required for efficient viral DNA replication. We also show that lytic replication leads to an S-phase-specific activation of the DNA damage response (DDR) that is abrogated when lytic replication is restricted to G0/G1. Finally, we observe that expression of early lytic viral genes results in cellular replication stress with increased stalling of DNA replication forks. Overall, we demonstrate that S-phase entry is important for optimal KSHV replication, that G1 arresting compounds are effective inhibitors of viral propagation, and that lytic-induced cell-cycle arrest could occur through the obstruction of cellular replication forks and subsequent activation of the DDR.
Induction of adaptive immune responses against antigens incorporated within the capsid of simian virus 40
Authors: Saika Kikue , Kato Masahiko , Sanada Hideaki , Matsushita Sho , Matsui Masanori , Handa Hiroshi , Kawano Masaaki
Published: June 2020

Simian virus 40 (SV40) is a monkey polyomavirus. The capsid structure is icosahedral and comprises VP1 units that measure 45 nm in diameter. Five SV40 VP1 molecules form one pentamer subunit, and a single icosahedral subunit comprises 72 pentamers; a single SV40 VP1 capsid comprises 360 SV40 VP1 molecules. In a previous study, we showed that an influenza A virus matrix protein 1 (M1) CTL epitope inserted within SV40 virus-like particles (VLPs) induced cytotoxic T lymphocytes (CTLs) without the need for an adjuvant. Here, to address whether SV40 VLPs induce adaptive immune responses against VLP-incorporated antigens, we prepared SV40 VLPs containing M1 or chicken ovalbumin (OVA). This was done by fusing M1 or OVA with the carboxyl terminus of SV40 VP2 and co-expressing them with SV40 VP1 in insect cells using a baculovirus vector. Intraperitoneal (i.p.) or intranasal administration of SV40 VLPs incorporating M1 induced the production of CTLs specific for the M1 epitope without the requirement for adjuvant. The production of antibodies against SV40 VLPs was also induced by i.p. administration of SV40 VLPs in the absence of adjuvant. Finally, the administration of SV40 VLPs incorporating OVA induced anti-OVA antibodies in the absence of adjuvant; in addition, the level of antibody production was comparable with that after i.p. administration of OVA plus alum adjuvant. These results suggest that the SV40 capsid incorporating foreign antigens can be used as a vaccine platform to induce adaptive immune responses without the need for adjuvant.
Moonstruck sleep: Synchronization of Human Sleep with the Moon Cycle under Natural Conditions
Authors: Casiraghi Leandro , Spiousas Ignacio , Dunster Gideon , McGlothlen Kaitlyn , Fernández-Duque Eduardo , Valeggia Claudia , de la Iglesia Horacio O.
Published: June 2020

As humans transitioned from hunter-gatherer to agricultural to highly urbanized post-industrial communities they progressively created environments that isolated sleep from its ancestral regulators, including the natural light-dark cycle. A prominent feature of this isolation is the availability of artificial light during the night, which delays the onset of sleep and shortens its duration. Before artificial light, moonlight was the only source of natural light sufficient to stimulate activity during the night; still, evidence for the modulation of sleep timing by lunar phases under natural conditions is controversial. Here we use data collected with wrist actimeters that measure daily sleep to show a clear synchronization of nocturnal sleep timing with the lunar cycle in participants who live in environments that range from a rural setting without access to electricity to a highly urbanized post-industrial one. The onset of sleep is delayed and sleep duration shortened as much as 1.5 hours on nights that precede the full moon night. Our data suggests that moonlight may have exerted selective pressure for nocturnal activity and sleep inhibition and that access to artificial evening light may emulate the ancestral effect of early-night moonlight.
Characteristics and Outcomes of Hospitalized Young Adults with Mild Covid-19
Authors: Sharma Arvind Kumar , Ahmed Asrar , Baig Vaseem Naheed , Dhakad Prahalad , Dalela Gaurav , Kacker Sudhanshu , Panwar Vasim Raja , Panwar Raja Babu , Gupta Rajeev
Published: June 2020

Background

Stormy course has been reported among hospitalized adults with covid-19 in high- and middle-income countries. To assess clinical outcomes in consecutively hospitalized patients with mild covid-19 in India we performed a study.

Methods

We developed a case registry of successive patients admitted with suspected covid-19 infection to our hospital (n=501). Covid-19 was diagnosed using reverse transcriptase polymerase chain reaction (RT-PCR). Demographic, clinical, investigations details and outcomes were recorded. Descriptive statistics are presented.

Results

Covid-19 was diagnosed in 234 (46.7%) and data compared with 267 (53.3%) negative controls. Mean age of covid-9 patients was 35.1±16.6y, 59.4% were <40y and 64% men. Symptoms were in less than 10% and comorbidities were in 4-8%. History of BCG vaccination was in 49% cases vs 10% controls. Cases compared to controls had significantly greater white cell (6.96+1.89 vs 6.12+1.69×109 cells/L) and lower lymphocyte count (1.98+0.79 vs 2.32+0.91×109 cells/L). No radiological and electrocardiographic abnormality was observed. All these were isolated or quarantined in the hospital and observed. Covid-19 patients received hydroxychloroquine and azithromycin according to prevalent guidelines. One patient needed oxygen support while hospital course was uncomplicated in the rest. All were discharged alive. Conversion to virus negative status was in 10.2±6.4 days and was significantly lower in age >40y (9.1±5.2) compared to 40-59y (11.3±6.1) and ≥60y (16.4±13.3) (p=0.001).

Conclusions

This hospital-based registry shows that mildly symptomatic or asymptomatic young covid-19 patients have excellent prognosis.

What is already known on this subject?

High rates of morbidity and mortality following hospitalization for covid-19 has been reported from most developed countries.

In most developing countries covid-19 patients with mild disease are also hospitalized due to lack of home isolation. Clinical outcome of such patients has not been well studied.

What this study adds?

We performed a clinical registry of successive young patients with mild covid-19 hospitalized with minimal symptoms and comorbidities.

None of the patients developed complications and all were discharged alive.
“Characteristics and stability of sensorimotor activity driven by isolated-muscle group activation in a human with tetraplegia”
Authors: Nickl Robert W. , Anaya Manuel A. , Thomas Tessy M. , Fifer Matthew S. , Candrea Daniel N. , McMullen David P , Thompson Margaret C. , Osborn Luke E. , Anderson William S. , Wester Brock A. , Tenore Francesco V. , Crone Nathan E. , Cantarero Gabriela L. , Celnik Pablo A.
Published: June 2020

Understanding cortical movement representations and their stability can shed light on robust brain-machine interface (BMI) approaches to decode these representations without frequent recalibration. Here, we characterize the spatial organization (somatotopy) and stability of the bilateral sensorimotor map of forearm muscles in an incomplete-high spinal-cord injury study participant implanted bilaterally in the primary motor and sensory cortices with Utah microelectrode arrays (MEAs).

We built the map by recording multiunit activity (MUA) and surface electromyography (EMG) as the participant executed (or attempted) contractions of 2 wrist muscles on each side of the body. To assess stability, we repeatedly mapped and compared left--wrist--extensor-related activity throughout several sessions, comparing somatotopy of active electrodes and neural signals both at the within-electrode (multiunit) and cross-electrode (network) levels.

Body maps showed significant activation in motor and sensory cortical electrodes, with fractured, intermixed representations of both intact and paralytic muscles. Within electrodes, firing strength stability decreased with time, with higher stability observed in sensory cortex than in motor, and in the contralateral hemisphere than in the ipsilateral. However, we observed no differences at network level, and no evidence of decoding instabilities for wrist EMG, either across timespans of hours or days, or across recording area. These results demonstrate first-time construction of a bilateral human sensorimotor map with MEAs. Further, while map stability differs between brain area and hemisphere at multiunit/electrode level, these differences are nullified at ensemble level.
The use of germicidal ultraviolet light, vaporised hydrogen peroxide and dry heat to decontaminate face masks and filtering respirators contaminated with a SARS-CoV-2 surrogate virus
Authors: Ludwig-Begall Louisa F. , Wielick Constance , Dams Lorène , Nauwynck Hans , Demeuldre Pierre-Francois , Napp Aurore , Laperre Jan , Haubruge Eric , Thiry Etienne
Published: June 2020

Background

In the context of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the supply of personal protective equipment remains under severe strain. To address this issue, re-use of surgical face masks and filtering facepiece respirators has been recommended; prior decontamination is paramount to their re-use.

Aim

We aim to provide information on the effects of three decontamination procedures on porcine respiratory coronavirus (PRCV)-contaminated masks and respirators, presenting a stable model for infectious coronavirus decontamination of these typically single-use-only products.

Methods

Surgical masks and filtering facepiece respirator coupons and straps were inoculated with infectious PRCV and submitted to three decontamination treatments, UV irradiation, vaporised H2O2, and dry heat treatment. Viruses were recovered from sample materials and viral titres were measured in swine testicle cells.

Findings

UV irradiation, vaporised H2O2 and dry heat reduced infectious PRCV by more than three orders of magnitude on mask and respirator coupons and rendered it undetectable in all decontamination assays.

Conclusion

This is the first description of stable disinfection of face masks and filtering facepiece respirators contaminated with an infectious SARS-CoV-2 surrogate using UV irradiation, vaporised H2O2 and dry heat treatment. The three methods permit demonstration of a loss of infectivity by more than three orders of magnitude of an infectious coronavirus in line with the FDA policy regarding face masks and respirators. It presents advantages of uncomplicated manipulation and utilisation in a BSL2 facility, therefore being easily adaptable to other respirator and mask types.
The upper respiratory tract microbiome of indigenous Orang Asli in north-eastern Peninsular Malaysia
Authors: Cleary D. W. , Morris D. E. , Anderson R. A. , Jones J. , Alattraqchi A. G. , Rahman N. I. A. , Ismail S. , Razali M. S. , Mohd Amin R. , Abd Aziz A. , Esa N. K. , Amiruddin S. , Chew C. H. , Amat Simin M. H. , Abdullah R. , Yeo C. C. , Clarke S. C.
Published: June 2020

Background

Microbiome research has focused on populations that are predominantly of European descent, and from narrow demographics that do not capture the socio-economic and lifestyle differences which impact human health. This limits our understanding of human-host microbiota interactions in their broadest sense. Here we examined the airway microbiology of the Orang Asli, the indigenous peoples of Malaysia. In addition to exploring the carriage and antimicrobial resistance of important respiratory pathobionts, we also present the first investigation of the nasal microbiomes of these indigenous peoples, in addition to their oral microbiomes.

Results

A total of 130 participants were recruited to the study from Kampung Sungai Pergam and Kampung Berua, both sites in the north-eastern state of Terengganu in Peninsular Malaysia. High levels ofStaphylococcus aureuscarriage were observed, particularly in the 18-65 age group (n=17/36; 47.2% 95%CI: 30.9-63.5). The highest carriage of pneumococci was in the <5 and 5 to 17 year olds, with 57.1% (4/7) and 49.2% (30/61) respectively. Sixteen pneumococcal serotypes were identified, the most common being the non-vaccine type 23A (14.6%) and the vaccine type 6B (9.8%). The nasal microbiome was significantly more diverse in those aged 5-17 years compared to 50+ years (p = 0.023). In addition, samples clustered by age (PERMANOVA analysis of the Bray-Curtis distance,p= 0.001). Hierarchical clustering of Bray-Curtis dissimilarity scores revealed six microbiome types. The largest cluster (n=28; 35.4%) had a marked abundance ofCorynebacterium.

Others comprisedCorynebacteriumwithDolosigranulum, two clusters were definable by the presence ofMoraxella, one with and the other withoutHaemophilus, a small grouping ofDelftia/ Ochrobactumprofiles and one withStreptococcus. NoStaphylococcusprofiles were observed. In the oral microbiomesStreptococcus, NeisseriaandHaemophiluswere dominant. Lower levels ofPrevotella, Rothia, Porphyromonas, VeillonellaandAggregatibacterwere also among the eight most observed genera.

Conclusions

We present the first study of Orang Asli airway microbiomes and pathobiont microbiology. Key findings include the prevalence of pneumococcal serotypes that would be covered by pneumococcal conjugate vaccines if introduced into a Malaysian national immunisation schedule, and the high level ofS. aureuscarriage. The dominance ofCorynebacteriumin the airway microbiomes is particularly intriguing given its’ consideration as a potentially protective commensal with respect to acute infection and respiratory health.
Relationship between input connectivity, morphology and orientation tuning of layer 2/3 pyramidal cells in mouse visual cortex
Authors: Weiler Simon , Nilo Drago Guggiana , Bonhoeffer Tobias , Hübener Mark , Rose Tobias , Scheuss Volker
Published: June 2020

Neocortical pyramidal cells (PCs) display functional specializations defined by their excitatory and inhibitory circuit connectivity. For layer 2/3 (L2/3) PCs, little is known about the detailed relationship between their neuronal response properties, dendritic structure and their underlying circuit connectivity at the level of single cells. Here, we ask whether L2/3 PCs in mouse primary visual cortex (V1) differ in their functional intra- and interlaminar connectivity patterns, and how this relates to differences in visual response properties. Using a combined approach, we first characterized the orientation and direction tuning of individual L2/3 PCs within vivo2-photon calcium imaging. Subsequently, we performed excitatory and inhibitory synaptic input mapping of the same L2/3 PCs in brain slices using laser scanning photostimulation (LSPS).

Our data from this structure-connectivity-function analysis show that the sources of excitatory and inhibitory synaptic input are different in their laminar origin and horizontal location with respect to cell position: On average, L2/3 PCs receive more inhibition than excitation from within L2/3, whereas excitation dominates input from L4 and L5. Horizontally, inhibitory input originates from locations closer to the horizontal position of the soma, while excitatory input arises from more distant locations in L4 and L5. In L2/3, the excitatory and inhibitory inputs spatially overlap on average. Importantly, at the level of individual neurons, PCs receive inputs from presynaptic cells located spatially offset, vertically and horizontally, relative to the soma. These input offsets show a systematic correlation with the preferred orientation of the postsynaptic L2/3 PCin vivo. Unexpectedly, this correlation is higher for inhibitory input offsets within L2/3 than for excitatory input offsets. When relating the dendritic complexity of L2/3 PCs to their orientation tuning, we find that sharply tuned cells have a less complex apical tree compared to broadly tuned cells. These results indicate that the spatial input offsets of the functional input connectivity are linked to orientation preference, while the orientation selectivity of L2/3 PCs is more related to the dendritic complexity.
Internal timing-related dopaminergic dynamics can be explained by reward-prediction errors
Authors: Hamilos Allison E. , Assad John A.
Published: June 2020

Dopaminergic neurons (DANs) exhibit complex dynamics across a variety of behavioral contexts, often in ways that seem task-specific and even incompatible with results across different paradigms. Dopaminergic signaling during timing tasks has been a prime example. In behavioral timing, dopaminergic dynamics predict the initiation of self-timed movement via a seconds-long ramp up of activity prior to movement onset, similar to ramping seen in visuospatial reward approach and multi-step, goal-directed behaviors. By contrast, in perceptual timing, DANs exhibit more complex dynamics whose direction of modulation seems to be theoppositeof that observed in behavioral timing. Mikhael et al. (2022) recently proposed a formal model in which dopaminergic dynamics encode reward expectation in the form of an “ongoing” reward-prediction error (RPE) that arises from resolving uncertainty of one’s position in the value landscape (i.e., one’s spatial-temporal distance to reward delivery/omission). Here, we show that application of this framework recapitulates and reconciles the seemingly contradictory dopaminergic dynamics observed in behavioralvsperceptual timing. These results suggest a common neural mechanism that broadly underlies timing behavior: trial-by-trial variation in the rate of the internal “pacemaker,” manifested in DAN signals that reflect stretching or compression of the derivative of the subjective value function relative to veridical time. In this view, faster pacemaking is associated with relatively high amplitude dopaminergic signaling, whereas slower pacemaking is associated with relatively low levels of dopaminergic signaling, consistent with findings from pharmacological and lesion studies.
20 years of African Neuroscience: Waking a sleeping giant
Authors: Maina MB , Ahmad U , Ibrahim HA , Hamidu SK , Nasr FE , Salihu AT , Abushouk AI , Abdurrazak M , Awadelkareem MA , Amin A , Imam A , Akinrinade ID , Yakubu AH , Azeez IA , Yunusa GM , Adamu AA , Ibrahim HB , Bukar AM , Yaro AU , Prieto-Godino LL , Baden T
Published: June 2020

Understanding the function and dysfunction of the brain remains one of the key challenges of our time. However, an overwhelming majority of brain research is carried out in the Global North, by a minority of well-funded and intimately interconnected labs. In contrast, with an estimated one neuroscientist per million people in Africa, news about neuroscience research from the Global South remains sparse. Clearly, devising new policies to boost Africa’s neuroscience landscape is imperative. However, the policy must be based on accurate data, which is largely lacking. Such data must reflect the extreme heterogeneity of research outputs across the continent’s 54 countries distributed over an area larger than USA, Europe and China combined. Here, we analysed all of Africa’s Neuroscience output over the past 21 years. Uniquely, we individually verified in each of 12,326 publications that the work was indeed performed in Africa and led by African-based researchers. This step is critical: previous estimates grossly inflated figures, because many of Africa’s high-visibility publications are in fact the result of internationally led collaborations, with most work done outside of Africa. The remaining number of African-led Neuroscience publications was 5,219, on average only ~5 per country and year. From here, we extracted metrics such as the journal and citations, as well as detailed information on funding, international collaborations and the techniques and model systems used. We link these metrics to demographic data and indicators of mobility and economy. For reference, we also extracted the same metrics from 220 randomly selected publications each from the UK, USA, Australia, Japan and Brazil. Our unique dataset allows us to gain accurate and in-depth information on the current state of African Neuroscience research, and to put it into a global context. This in turn allows us to make actionable recommendations on how African research might best be supported in the future.
Mathematical modeling of ventilator-induced lung inflammation
Authors: Minucci Sarah , Heise Rebecca L. , Valentine Michael S. , Kamga Gninzeko Franck J. , Reynolds Angela M.
Published: June 2020

Respiratory infections, such as the novel coronavirus (SARS-COV-2) and other lung injuries, damage the pulmonary epithelium. In the most severe cases this leads to acute respiratory distress syndrome (ARDS). Due to respiratory failure associated with ARDS, the clinical intervention is the use of mechanical ventilation. Despite the benefits of mechanical ventilators, prolonged or misuse of these ventilators may lead to ventilation-associated/ventilation-induced lung injury (VILI). Damage caused to epithelial cells within the alveoli can lead to various types of complications and increased mortality rates. A key component of the immune response is recruitment of macrophages, immune cells that differentiate into phenotypes with unique pro- and/or anti-inflammatory roles based on the surrounding environment. An imbalance in pro- and anti-inflammatory responses can have deleterious effects on the individual’s health. To gain a greater understanding of the mechanisms of the immune response to VILI and post-ventilation outcomes, we develop a mathematical model of interactions between the immune system and site of damage while accounting for macrophage polarization. Through Latin hypercube sampling we generate a virtual cohort of patients with biologically feasible dynamics. We use a variety of methods to analyze the results, including a random forest decision tree algorithm and parameter sensitivity with eFAST. Analysis shows that parameters and properties of transients related to epithelial repair and M1 activation and de-activation best predicted outcome. Using this new information, we hypothesize inter-ventions and use these treatment strategies to modulate damage in select virtual cases.
Sustained attention and vigilance deficits associated with HIV and a history of methamphetamine dependence
Authors: Pocuca Nina , Young Jared W. , MacQueen David A. , Letendre Scott , Heaton Robert K. , Geyer Mark A. , Perry William , Grant Igor , Minassian Arpi ,   the Translational Methamphetamine AIDS Research Center (TMARC)
Published: June 2020

Background

Human immunodeficiency virus (HIV)-associated neurocognitive disorders persist in the era of antiretroviral therapy (ART). One factor that is elevated among persons with HIV (PWH) and independently associated with neurocognitive impairment is methamphetamine dependence (METH+). Such dependence may further increase cognitive impairment among PWH, by delaying HIV diagnosis (and thus, ART initiation), which has been posited to account for persistent cognitive impairment among PWH, despite subsequent treatment-related viral load suppression (VLS; ≤50 copies of the virus per milliliter in plasma or cerebrospinal fluid). This study examined the independent and combined (additive versus synergistic) effects of HIV and history of METH+ on the sustained attention and vigilance cognitive domain, while controlling for VLS.

Methods

Participants included 205 (median age=44 years; 77% males; HIV-/METH-n=67; HIV+/METH -n=49; HIV-/METH+n=36; HIV+/METH+n=53) individuals enrolled in the Translational Methamphetamine AIDS Research Center, who completed Conners’ and the 5- Choice continuous performance tests (CPTs).

Results

METH+ participants exhibited deficits in sustained attention and vigilance; however, these effects were not significant after excluding participants who had a positive urine toxicology screen for methamphetamine. Controlling for VLS, PWH did not have worse sustained attention and vigilance, but consistently displayed slower reaction times across blocks, relative to HIV-participants. There was no HIV x METH interaction on sustained attention and vigilance.

Conclusions

Recent methamphetamine use among METH+ people and detectable viral loads are detrimental to sustained attention and vigilance. These findings highlight the need for prompt diagnosis of HIV and initiation of ART, and METH use interventions.
Massively parallel functional testing ofMSH2missense variants conferring Lynch Syndrome risk
Authors: Jia Xiaoyan , Burugula Bala Bharathi , Chen Victor , Lemons Rosemary M. , Jayakody Sajini , Maksutova Mariam , Kitzman Jacob O.
Published: June 2020

The lack of functional evidence for the majority of missense variants limits their clinical interpretability, and poses a key barrier to the broad utility of carrier screening. In Lynch Syndrome (LS), one of the most highly prevalent cancer syndromes, nearly 90% of clinically observed missense variants are deemed “variants of uncertain significance” (VUS). To systematically resolve their functional status, we performed a massively parallel screen in human cells to identify loss-of-function missense variants in the key DNA mismatch repair factorMSH2. The resulting functional effect map is substantially complete, covering 94% of the 17,746 possible variants, and is highly concordant (96%) with existing functional data and expert clinicians’ interpretations. The large majority (89%) of missense variants were functionally neutral, perhaps unexpectedly in light of its evolutionary conservation. These data provide ready-to-use functional evidence to resolve the ∼1,300 extant missense VUSs inMSH2, and may facilitate the prospective classification of newly discovered variants in the clinic.
Sex differences in the progression from NAFL to NASH: a functional meta-analysis of transcriptomic studies
Authors: Català-Senent José F. , Hidalgo Marta R. , Berenguer Marina , Parthasarathy Gopanandan , Malhi Harmeet , Malmierca-Merlo Pablo , de la Iglesia-Vayá María , García-García Francisco
Published: June 2020

Background & aims

Sex differences in non-alcoholic fatty liver disease (NAFLD) are well known and yet, most of the studies available in the literature do not include this factor when analysing the data. Here we present a functional meta-analysis of NAFLD studies to detect the molecular mechanisms involved in its progression, distinguishing any differences relative to patient sex.

Methods

We systematically reviewed the Gene Expression Omnibus (GEO) database functional Gene Ontology (GO) terms detailed in transcriptomic studies, following the PRISMA statement guidelines. For each study, we compared the progression from steatosis (NAFL) to steatohepatitis (NASH) in premenopausal women and men using a dual strategy: a gene-set analysis and a pathway activity analysis. The functional results of all the studies were integrated in a meta-analysis.

Results

A total of 114 abstracts were reviewed and 7 studies, which included 323 eligible patients, were finally analysed. The meta-analyses highlighted significant functions in both sexes. In premenopausal women, the overrepresented functions referred to DNA regulation, vinculin binding, IL-2 responses, negative regulation of neuronal death, and the transport of ions and cations. In men, they referred to the negative regulation of IL-6 and the establishment of planar polarity involved in neural tube closure.

Conclusions

Our meta-analysis of this transcriptomic data provides a powerful approach to identify sex differences in the progression from NAFL to NASH. We detected relevant biological functions and molecular terms that were affected differently between premenopausal women and men. Changes in the immune responsiveness between men and women with NAFLD suggested that women have a more immune tolerant milieu while men have an impaired liver regenerative response.

Introductory Statement

Progression from NAFL to NASH differently affects cellular functions in women and men. Here we systematically reviewed publicly available transcriptomic data and then performed a meta-analysis to find these affected functions. Thus, we identified 13 biological functions implicated in the progression of NAFLD that were differentially affected by sex.

Graphical abstract
The psychological effects of COVID-19 on frontline healthcare workers and how they are coping: a web-based, cross-sectional study from Pakistan
Authors: Salman Muhammad , Raza Muhammad Husnnain , Ul Mustafa Zia , Khan Tahir Mehmood , Asif Noman , Tahir Humera , Shehzadi Naureen , Hussain Khalid
Published: June 2020

Background

High level stress is expected when crises starts affecting people’s lives and communities which is witnessed in the past epidemics. Infectious diseases outbreaks like the ongoing COVID19 pandemic have negative impact on healthcare workers’ (HCWs) mental health, which needs to be investigated. Therefore, we aimed to assess the psychological impact of COVID-19 on frontline HCWs and their coping strategies.

Methods

A web-based, cross-sectional study was conducted among HCWs of the Punjab province of Pakistan. The generalized anxiety scale (GAD-7), patient health questionnaire (PHQ-9) and Brief-COPE were used to assess anxiety, depression and coping strategies.

Results

The mean age of respondents (N = 398) was 28.67 ± 4.15 years, with majority of medical doctors (52%). The prevalence of anxiety and depression were 21.4% and 21.9%, respectively. There was no significant difference of anxiety and depression scores among doctors, nurses and pharmacists. Females had significantly higher anxiety (p = 0.003) and depression (p = 0.001) scores than males. Moreover, HCWs performing duties in COVID-19 ICU had significantly higher anxiety score than those from isolation wards (p = 0.020) and other departments (p = 0.014). Depression, not anxiety, score were higher among those who did not receive the infection prevention training. Most frequently adopted coping strategy was religious coping (5.98 ± 1.73) followed by acceptance (5.59 ± 1.55) and coping planning (4.91 ± 1.85).

Conclusion

A considerable proportion of HCWs are having generalized anxiety and depression during the ongoing COVID-19 pandemic. Our findings call for interventions to mitigate mental health risks in HCWs.
Strength of attention-sampling parietal EEG theta rhythm is linked to impaired inhibition in adult ADHD
Authors: Juurmaa Kristiina , Palomäki Jussi , Cowley Benjamin Ultan
Published: June 2020

Attention-deficit hyperactivity disorder (ADHD) in adults is understudied, especially regarding neural mechanisms such as oscillatory control of attention sampling. We report an EEG study of such cortical oscillations, in ADHD-diagnosed adults taking a continuous performance test that measures the ability to sustain attention and inhibit impulsivity for a prolonged period of time.

We recorded 53 adults (28f, 25m, aged 18-60), and 18 matched healthy controls, using 128-channel EEG. We analysed features with established links to neural correlates of attention: event-related (de)synchronisation (ERS), alpha and theta frequency band activation, and stimulus-locking indices; in frontal and parietal scalp regions.

Test performance distinguished healthy controls from ADHD adults. The ADHD group manifested significantly less parietal 4 Hz theta ERS during correct inhibition trials, in addition to having greater sensitivity to targets in stimulus-locking measures.

Our results suggest that ADHD adults have impaired attention sampling in relational categorisation tasks.