bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic value of cervical ligamentum flavum thickness as a morphological parameter to predict cervical stenosis
Authors: Jeong Hye-Won , Yi Jungmin , Lee Sooho , Park Sukhee , Kang Keum Nae , Lee Jonghyuk , Cho Hyung Rae , Kim Young Uk
Published: August 2021

One of major causes of cervical central stenosis (CCS) is thickened change of cervical ligament flavum (CLF). The association of a morphological parameter called cervical ligament flavum thickness (CLFT) with CCS has not been reported yet. Thus, the purpose of this research was to investigate the relationship between CCS and CFJT.

Data were obtained from 88 patients with CCS. A total of 87 normal controls also underwent cervical spine magnetic resonance imaging (CSMRI). All subjects underwent axial T2-weighted CSMRI. Using our picture archiving and communications system, thickness of ligament flavum of the cervical spine at C6/7 level was analyzed.

The mean CLFT was 1.41 ± 0.24 mm in normal subjects and 2.09 ± 0.39 mm in patients with CCS. The CCS group was found to have significantly (P < .001) higher rate of CLFT than normal subjects. ROC curves were used to assess the usefulness of CLFT as a predictor of CCS. In the CCS group, the best practical cut off-point of CLFT was 1.71 mm (sensitivity = 90.9%; specificity = 90.8%), with AUC of 0.94 (95% confidence interval: 0.90--0.98).

Greater CLFT values were associated with greater possibility of CCS. Thus, treating physician should carefully examine CLFT, as it can help diagnose CCS.
Cutoff point of neutrophil-to-lymphocyte ratio for predicting survival in nasopharyngeal carcinoma
Authors: Setakornnukul Jiraporn , Chanvimalueng Waipoj , Patumanond Jayanton , Thephamongkhol Kullathorn
Published: August 2021

Neutrophil-to-lymphocyte ratio (NLR) was reported as an independent prognostic factor in many studies, but its cutoff point was not yet concluded. We set forth to prove and validate cutoff point of NLR as a poor prognostic factor for overall survival (OS) in nonmetastatic nasopharyngeal carcinoma (NPC) patients.

Retrospective cohort of nonmetastatic NPC adult patients treated with intensity-modulated radiotherapy with curative aim at Siriraj hospital during 2007 to 2014 was enrolled. NLR was defined as absolute neutrophil count divided by absolute lymphocyte count. OS was the primary outcome. We explored our cutoff value by maximum concordance index (C-index) method, and we validated our cutoff and previously reported cutoff values by categorizing patients as NLR ≤ 3 or >3. Internal validation was done by bootstrapping method.

Four hundred sixty-three patients were included. The median follow-up time was 70.8 months. By the end of June 2019, 211 patients had died. In univariable analysis of OS by Cox model, an NLR value of 3 showed the highest C-index (0.548) with an HR of 1.43 (95% CI: 1.08–1.89). After adjustment for body mass index, overall staging, age, gender, and histology in multivariable analysis, an NLR >3 was still an independent prognostic factor of poor OS (HR = 1.34, 95% CI = 1.01–1.79). After internal validation, the resampling method shows no overfitting condition and corrected C-index was 0.547 for univariable analysis.

A cutoff point of NLR of 3 from routine blood test was found to be an independent poor prognostic factor among patients with nonmetastatic NPC. This prognostic factor could be included in clinical prediction model of NPC and this further prediction model would select high risk patients for intensive treatment.
Depression
Authors: Naguy Ahmed , Pridmore Saxby , Abuzeid Mohamed Y. , Thiguti Sri Haricharan , Alamiri Bibi
Published: August 2021

Burgeoning body of evidence from neuroscience is pouring in highlighting a potential association between gut microbiota with the pathophysiology of depression and anxiety. Manipulation of gut microbiota may be then useful to decode this role and to provide novel therapeutics for major depressive disorder (MDD), developing microbiota-related biomarkers to stratify patients at risk and to delineate more homogeneous biotypes of MDD.
Schizophrenia and Dental Health
Authors: Comparelli Anna , Stampatore Lorenzo , Costacurta Micaela , Pompili Maurizio
Published: August 2021

Schizophrenia is characterized not only by psychopathological symptoms but also by medical comorbidities. Among the latter, there are limited data on dental health. We conducted a systematic review with the primary aim of clarifying the extent of the relationship between dental diseases and schizophrenia. The second aim was to delineate an intervention program based on illness-related factors that influence dental health. The preferred reporting items for systematic reviews and meta-analyses statement for reporting systematic reviews was used. Only articles published in English language peer-reviewed journals were considered; we excluded case reports, meta-analyses, and systematic reviews, as well as studies that did not clearly report statistical analysis, diagnostic criteria, or the number of patients included. Twenty-one studies comprising 13,110 patients with schizophrenia and 9025 healthy controls were included. Negative symptomatology, long duration of illness, smoking habit, drug-induced xerostomia, and neuroinflammation are the most critical areas. We suggest an intervention program for prevention and treatment of dental diseases in schizophrenia.
Role of Social Media in Psychiatry During Pandemic
Authors: Memon Roha Saeed , Ullah Irfan , Shoib Sheikh , Qudrat Qudrat Ullah , de Filippis Renato
Published: August 2021

The COVID-19 pandemic brought with itself significant mental health challenges owing not only to the morbidity and mortality from the infection but also to mitigation strategies of social distancing and self-isolation. Indeed, in the absence of adequate pharmaceutical aids, quarantine and social distancing measures are taken to limit the spread of the SARS-CoV-2 virus. Thus, living in the world of social media, the average usage of social media could be expected to show a sharp rise as measures of social distancing and quarantine are adopted to contain the pandemic. In this context, social media could be thought of as an additional preventative resource aiding the containment of the pandemic by being a key network for communication during a crisis.

Because social media usage cannot be brought down to null considering the fact that it does have some positive aspects to it in terms of disposition of useful information, we could alternatively modify the reporting to be more responsible.

In conclusion, we could hypothesize that social media might surge responses for some adverse mental health conditions, increasing fear, anxiety, and panic responses, even spreading suicidal ideation and therefore impacting incidence of suicide in some way. Moreover, social media should be carefully handled, particularly during the pandemic, as social media engagement spiked. Indeed, suicide news, when not reported adequately, and most dangerous social media challenges could have devastating effects among youngest users.
Lessons From a Quality Improvement Project to Standardize the Process of Gastric Biopsy Culture for Helicobacter pylori
Authors: Bonilla Silvana , Bousvaros Athos , Cardini Jeff , Estrella-Pimentel Loida , Mitchell Paul D. , Goldshine Jana , Hirsch Rebecca , Jonas Maureen , Fox Victor
Published: August 2021

Background:

Despite expert recommendations, clinician’s adherence to pediatric societal clinical practice guidelines is variable, particularly with respect to the use of gastric biopsy culture in the initial diagnosis of Helicobacter pylori infection. In addition, the implementation of routine use of gastric biopsy culture has been challenging with several factors affecting the rate of successful primary H pylori culture.

Methods:

We conducted a quality improvement (QI) project with the aims of increasing the rate of successful primary culture. The QI project involved educational efforts among our gastroenterologists, endoscopy suite personnel, and laboratory personnel. We compared the frequency of gastric biopsy culture sent in patients with international classification of diseases 9th revision code 041.86, and 10th revision codes B96.81 evaluated by pediatric gastroenterologists at Boston Children’s Hospital during the 9 months before the QI intervention (February 1, 2019 to October 31, 2019) and 9 months after the QI intervention (November 1 2019 to July 31 2020). We also compared the rate of culture growth in patients with positive histology (culture positivity), and antimicrobial susceptibilities before and after November 1, 2019.

Results:

We observed an increased frequency of gastric biopsy acquisition by any gastroenterologist, obtained in 39% (28 of 71) preintervention patients compared with 67% (36 of 54) intervention patients (P = 0.004). There was an increase in the percentage of culture positivity across study periods from 21% (3 of 14) preintervention to 45% (5 of 11) postintervention (P = 0.39; 95% confidence interval, 0.64-7.00).

Conclusion:

Educational initiatives and collaborative work with staff physicians, endoscopy personnel, and hospital laboratory appear to be effective tools to increase usage of gastric biopsy culture as a diagnostic tool for H pylori infection and to increase culture positivity. Improving the surveillance of local resistance rates will improve the selection of the most effective primary treatment in specific geographic areas.
Prevalence of Diaphragmatic Dysfunction in the Long-Term Acute Care Setting and Its Effects on Ventilator Weaning Outcomes
Authors: Barchuk Alex , Barchuk Sofia A. , Roebken Curtis K. , Ahn Jaeil
Published: August 2021

Objective

To determine the prevalence of undiagnosed diaphragmatic dysfunction in a long-term acute care hospital setting in patients on prolonged mechanical ventilation and its association with weaning outcomes.

Design

This is a single-center, retrospective cohort study including 451 patients on prolonged mechanical ventilation admitted to a long-term acute care hospital facility between 2012 and 2017. Diaphragmatic dysfunction was assessed using fluoroscopy.

Results

Three hundred nineteen patients on prolonged mechanical ventilation were assessed for diaphragmatic dysfunction. Nine patients were diagnosed with diaphragmatic dysfunction before admission. Eighty (72.7%) without diaphragmatic dysfunction were successfully weaned and 30 (27.3%) failed to wean, whereas 51 participants (31.9%) with diaphragmatic dysfunction were successfully weaned and 109 (68.1%) failed to wean (P < 0.001). When analyzing days to wean, the median was 13 days for those with no diaphragmatic dysfunction, 19 days with unilateral diaphragmatic dysfunction, and 28 days with bilateral diaphragmatic dysfunction (P < 0.001). Weaning success was not statistically associated with generalized neuromuscular disorders, age, sex, body mass index, smoking history, or diabetes.

Conclusions

Diaphragmatic dysfunction was found to be strongly associated with time to wean and weaning success in the long-term acute care hospital setting. Very few patients despite being on prolonged mechanical ventilation were diagnosed with diaphragmatic dysfunction before long-term acute care hospital admission. Given this information, early diagnosis of diaphragmatic dysfunction among prolonged mechanical ventilation patients in the long-term acute care hospital setting is paramount in preventing secondary complications associated with mechanical ventilation.
Five Years With Dolutegravir Plus Lamivudine as a Switch Strategy: Much More Than a Positive Finding
Authors: Ciccullo Arturo , Borghi Vanni , Giacomelli Andrea , Cossu Maria Vittoria , Sterrantino Gaetana , Latini Alessandra , Giacometti Andrea , De Vito Andrea , Gennari William , Madeddu Giordano , Capetti Amedeo , d’Ettorre Gabriella , Mussini Cristina , Rusconi Stefano , Di Giambenedetto Simona , Baldin Gianmaria
Published: August 2021

Background:

Results from clinical trials and observational studies suggest that dolutegravir plus lamivudine could be an effective and well-tolerated option for simplification in HIV-1–positive patients. We aimed to assess long-time efficacy and safety in our multicenter cohort.

Methods:

This was a retrospective study enrolling HIV-1–infected, virologically suppressed patients switching to dolutegravir + lamivudine. We performed survival analysis to evaluate time to virological failure (VF, defined by a single HIV-RNA ≥1000 copies/mL or by 2 consecutive HIV-RNA ≥ 50 copies/mL) and treatment discontinuation (defined as the interruption of either 3TC or dolutegravir), assessing predictors via Cox regression analyses.

Results:

Seven-hundred eighty-five patients were considered for the analysis: 554 were men (70.6%), with a median age of 52 years (interquartile range 45–58 years). Estimated probabilities of maintaining virological suppression at weeks 96, 144, and 240 were 97.7% (SD ±0.6), 96.9% (SD ±0.8), and 96.4% (SD ±0.9), respectively. A non-B HIV subtype (P = 0.014) and a previous VF (P = 0.037) resulted predictors of VF. We did not observe differences in probability of VF in people living with HIV with an M184V resistance mutation (P = 0.689); however, in a deeper analysis, M184V mutation was a predictor of VF (P = 0.038) in patients with time of virological suppression <88 months. Estimated probabilities of remaining on study regimen at 96, 144, and 240 weeks were 82.9% (SD ±1.4), 79.7% (SD ±1.6) and 74.3% (SD ±2.2), respectively.

Conclusions:

Our findings show the long-term efficacy and tolerability of dolutegravir plus lamivudine in virologically suppressed patients.
Shining light on a deep-sea bacterial symbiont population structure with CRISPR
Authors: Perez Maëva , Angers Bernard , Young C. Robert , Juniper S. Kim
Published: August 2021

Many foundation species in chemosynthesis-based ecosystems rely on environmentally acquired symbiotic bacteria for their survival. Hence, understanding the biogeographic distributions of these symbionts at regional scales is key to understanding patterns of connectivity and predicting resilience of their host populations (and thus whole communities). However, such assessments are challenging because they necessitate measuring bacterial genetic diversity at fine resolutions. For this purpose, the recently discovered clustered regularly interspaced short palindromic repeats (CRISPR) constitutes a promising new genetic marker. These DNA sequences harboured by about half of bacteria hold their viral immune memory, and as such, might allow discrimination of different lineages or strains of otherwise indistinguishable bacteria. In this study, we assessed the potential of CRISPR as a hypervariable phylogenetic marker in the context of a population genetic study of an uncultured bacterial species. We used high-throughput CRISPR-based typing along with multi-locus sequence analysis (MLSA) to characterize the regional population structure of the obligate but environmentally acquired symbiont species Candidatus Endoriftia persephone on the Juan de Fuca Ridge. Mixed symbiont populations of Ca. Endoriftia persephone were sampled across individual Ridgeia piscesae hosts from contrasting habitats in order to determine if environmental conditions rather than barriers to connectivity are more important drivers of symbiont diversity. We showed that CRISPR revealed a much higher symbiont genetic diversity than the other housekeeping genes. Several lines of evidence imply this diversity is indicative of environmental strains. Finally, we found with both CRISPR and gene markers that local symbiont populations are strongly differentiated across sites known to be isolated by deep-sea circulation patterns. This research showed the high power of CRISPR to resolve the genetic structure of uncultured bacterial populations and represents a step towards making keystone microbial species an integral part of conservation policies for upcoming mining operations on the seafloor.
Genomics of Ochrobactrum pseudogrignonense (newly named Brucella pseudogrignonensis) reveals a new bla OXA subgroup
Authors: Li Shu-Yuan , Huang Yin-En , Chen Jhih-Yang , Lai Chung-Hsu , Mao Yan-Chiao , Huang Yao-Ting , Liu Po-Yu
Published: August 2021

Ochrobactrum pseudogrignonense(newly namedBrucella pseudogrignonensis) is an emerging pathogen in immunodeficient and immunocompetent patients. Most documented cases associated withOchrobactrumare frequently catheter-related and exhibit wide-spectrum β-lactam resistance. Misidentification of this pathogen using commercial bacterial identification kits is common. We identified a case ofO. pseudogrignonenseinfection associated with cholelithiasis. TheO. pseudogrignonensegenome was sequenced and reconstructed using a Nanopore and Illumina hybrid strategy. A novelblaOXA-919divergent from existing OXA members was identified and subsequent analysis revealed its existence in all availableO. pseudogrignonensegenomes, which forms a new phylogenetic subgroup distinct from other OXA clusters. Further analysis demonstrated the presence of the novelblaOXA-919in the chromosome of several otherOchrobactrumspecies. Our study indicated thatOchrobactrumchromosomes may be a reservoir ofblaOXA-919β-lactamases.
Adaptive response to wine selective pressures shapes the genome of a Saccharomyces interspecies hybrid
Authors: Lairón-Peris María , Castiglioni Gabriel L. , Routledge Sarah J. , Alonso-del-Real Javier , Linney John A. , Pitt Andrew R. , Melcr Josef , Goddard Alan D. , Barrio Eladio , Querol Amparo
Published: August 2021

During industrial processes, yeasts are exposed to harsh conditions, which eventually lead to adaptation of the strains. In the laboratory, it is possible to use experimental evolution to link the evolutionary biology response to these adaptation pressures for the industrial improvement of a specific yeast strain. In this work, we aimed to study the adaptation of a wine industrial yeast in stress conditions of the high ethanol concentrations present in stopped fermentations and secondary fermentations in the processes of champagne production. We used a commercialSaccharomyces cerevisiae × S. uvarumhybrid and assessed its adaptation in a modified synthetic must (M-SM) containing high ethanol, which also contained metabisulfite, a preservative that is used during wine fermentation as it converts to sulfite. After the adaptation process under these selected stressful environmental conditions, the tolerance of the adapted strain (H14A7-etoh) to sulfite and ethanol was investigated, revealing that the adapted hybrid is more resistant to sulfite compared to the original H14A7 strain, whereas ethanol tolerance improvement was slight. However, a trade-off in the adapted hybrid was found, as it had a lower capacity to ferment glucose and fructose in comparison with H14A7. Hybrid genomes are almost always unstable, and different signals of adaptation on H14A7-etoh genome were detected. Each subgenome present in the adapted strain had adapted differently. Chromosome aneuploidies were present inS. cerevisiaechromosome III and inS. uvarumchromosome VII–XVI, which had been duplicated. Moreover,S. uvarumchromosome I was not present in H14A7-etoh and a loss of heterozygosity (LOH) event arose onS. cerevisiaechromosome I. RNA-sequencing analysis showed differential gene expression between H14A7-etoh and H14A7, which can be easily correlated with the signals of adaptation that were found on the H14A7-etoh genome. Finally, we report alterations in the lipid composition of the membrane, consistent with conserved tolerance mechanisms.
Threat imminence reveals links among unfolding of anticipatory physiological response, cortical-subcortical intrinsic functional connectivity, and anxiety
Authors: Abend Rany , Ruiz Sonia G. , Bajaj Mira A. , Harrewijn Anita , Linke Julia O. , Atlas Lauren Y. , Pine Daniel S.
Published: August 2021

Excessive expression of threat-anticipatory defensive responses is central in anxiety. Animal research indicates that anticipatory responses are dynamically organized by threat imminence and rely on conserved circuitry. Insight from translational work on threat imminence could guide mechanistic research mapping abnormal function in this circuitry to aberrant defensive responses in anxiety. Here, we initiate such research.

Fifty pediatric anxiety patients and healthy-comparisons (33 females) completed a threat-anticipation task whereby cues signaled delivery of highly-painful (threat) or non-painful (safety) heat. Temporal changes in skin-conductance indexed defensive responding as function of threat imminence. Resting-state functional connectivity data were used to identify intrinsic-function correlates of anticipatory response within a specific functional network derived from translational research.

Results indicate that anxiety was associated with greater increase in anticipatory response as threats became more imminent. Magnitude of increase in threat-anticipatory responses corresponded to intrinsic connectivity within a cortical-subcortical circuit; importantly, more severe anxiety was associated with greater connectivity between ventromedial prefrontal cortex and hippocampus and basolateral amygdala, a circuit implicated in animal models of anxiety. These findings link basic-translational and clinical research, highlighting aberrant intrinsic function in conserved defensive circuitry as potential pathophysiological mechanism in anxiety.
Toward Using Twitter for PrEP-Related Interventions: An Automated Natural Language Processing Pipeline for Identifying Gay or Bisexual Men in the United States
Authors: Klein Ari Z. , Meanley Steven , O’Connor Karen , Bauermeister José A. , Gonzalez-Hernandez Graciela
Published: August 2021

Background

Pre-exposure prophylaxis (PrEP) is highly effective at preventing the acquisition of Human Immunodeficiency Virus (HIV). There is a substantial gap, however, between the number of people in the United States who have indications for PrEP and the number of them who are prescribed PrEP. While Twitter content has been analyzed as a source of PrEP-related data (e.g., barriers), methods have not been developed to enable the use of Twitter as a platform for implementing PrEP-related interventions.

Objective

Men who have sex with men (MSM) are the population most affected by HIV in the United States. Therefore, the objective of this study was to develop and assess an automated natural language processing (NLP) pipeline for identifying men in the United States who have reported on Twitter that they are gay, bisexual, or MSM.

Methods

Between September 2020 and January 2021, we used the Twitter Streaming Application Programming Interface (API) to collect more than 3 million tweets containing keywords that men may include in posts reporting that they are gay, bisexual, or MSM. We deployed handwritten, high-precision regular expressions on the tweets and their user profile metadata designed to filter out noise and identify actual self-reports. We identified 10,043 unique users geolocated in the United States, and drew upon a validated NLP tool to automatically identify their ages.

Results

Based on manually distinguishing true and false positive self-reports in the tweets or profiles of 1000 of the 10,043 users identified by our automated pipeline, our pipeline has a precision of 0.85. Among the 8756 users for which a United States state-level geolocation was detected, 5096 (58.2%) of them are in the 10 states with the highest numbers of new HIV diagnoses. Among the 6240 users for which a county-level geolocation was detected, 4252 (68.1%) of them are in counties or states considered priority jurisdictions by the Ending the HIV Epidemic (EHE) initiative. Furthermore, the majority of the users are in the same two age groups as the majority of MSM in the United States with new HIV diagnoses.

Conclusions

Our automated NLP pipeline can be used to identify MSM in the United States who may be at risk for acquiring HIV, laying the groundwork for using Twitter on a large scale to target PrEP-related interventions directly at this population.
COMORBIDITY ANALYSIS: OVERLAPPING SEMICIRCLES WITH WIGNER LAW AND RANDOM MATRIX THEORY
Authors: Nolasco-Jáuregui O. , Quezada-Téllez L. A. , Salazar-Flores Y. , Díaz-Hernández Adán
Published: August 2021

In December 2019 COVID-19 appeared as a new pandemic that has claimed the lives of millions of people around the world. This article presents a regional analysis of COVID-19 in Mexico. Due to the comorbidities of Mexican society, the new pandemic implies a higher risk for the population. The study period runs from April 12 to October 5, 2020 (761 665 Patients). In this proposal we apply a unique methodology of random matrix theory in the moments of a probability measure that appears as the limit of the empirical spectral distribution by the Wigner semicircle law. The graphical presentation of the results is done with Machine Learning methods in the SuperHeat maps. With this is possible to analyze the behavior of patients who tested positive for COVID-19 and their comorbidities. We conclude that the most sensitive comorbidities in hospitalized patients are the following three: COPD, Other Diseases and Renal Diseases.
Evaluation of GENECUBE® HQ SARS-CoV-2 for anterior nasal samples and saliva samples with a new rapid examination protocol
Authors: Naito Asami , Kiyasu Yoshihiko , Akashi Yusaku , Sugiyama Akio , Michibuchi Masashi , Takeuchi Yuto , Notake Shigeyuki , Nakamura Koji , Ishikawa Hiroichi , Suzuki Hiromichi
Published: August 2021

Introduction

GENECUBE® is a rapid molecular identification system, and previous studies demonstrated that GENECUBE® HQ SARS-CoV-2 showed excellent analytical performance for the detection of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) with nasopharyngeal samples. However, other respiratory samples have not been evaluated.

Methods

This prospective comparison between GENECUBE® HQ SARS-CoV-2 and reference real-time reverse transcriptase polymerase chain reaction (RT-PCR) was performed for the detection of SARS-CoV-2 using anterior nasal samples and saliva samples. Additionally, we evaluated a new rapid examination protocol using GENECUBE® HQ SARS-CoV-2 for the detection of SARS-CoV-2 with saliva samples. For the rapid protocol, in the preparation of saliva samples, purification and extraction processes were adjusted, and the total process time was shortened to approximately 35 minutes.

Results

For 359 anterior nasal samples, the total-, positive-, and negative concordance of the two assays was 99.7% (358/359), 98.1% (51/52), and 100% (307/307), respectively. For saliva samples, the total-, positive-, and negative concordance of the two assays was 99.6% (239/240), 100% (56/56), and 99.5% (183/184), respectively. With the new protocol, total-, positive-, and negative concordance of the two assays was 98.8% (237/240), 100% (56/56), and 98.4% (181/184), respectively. In all discordance cases, SARS-CoV-2 was detected by additional molecular examinations.

Conclusion

GENECUBE® HQ SARS-CoV-2 provided high analytical performance for the detection of SARS-CoV-2 in anterior nasal samples and saliva samples.
Use of HIV Recency Assays for HIV Incidence Estimation and Non-Incidence Surveillance Use Cases: A systematic review
Authors: Facente Shelley N. , Agyei Lillian , Maher Andrew D. , Mahy Mary , Dalal Shona , Lowrance David , Grebe Eduard , Marsh Kimberly
Published: August 2021

Introduction

HIV assays designed to detect recent infection, also known as “recency assays,” are often used to estimate HIV incidence in a specific country, region, or subpopulation, alone or as part of recent infection testing algorithms (RITAs). Recently, many countries and organizations have become interested in using recency assays within case surveillance systems and routine HIV testing services, and in measuring other indicators beyond incidence, generally referred to as “non-incidence surveillance use cases.”

Methods

To identify best methodological and field implementation practices for the use of recency assays to estimate HIV incidence and trends in recent infections for key populations or specific geographic areas, we undertook: 1) a global Call for Information released from WHO/UNAIDS; and 2) a systematic review of the literature to: (a) assess the field performance characteristics of commercially available recency assays, (b) understand the use of recency testing for surveillance in programmatic and laboratory settings, and (c) review methodologies for implementing recency testing for both incidence estimation and non-incidence use cases.

Results and discussion

Among the 90 documents ultimately reviewed, 65 (88%) focused on assay/algorithm performance or methodological descriptions, with high-quality evidence of accurate age- and sex- disaggregated HIV incidence estimation at national or regional levels in general population settings, but not at finer geographic levels for prevention prioritization. The remaining 25 documents described field-derived incidence (n=14) and non-incidence (n=11) use cases, including integrating RITAs into routine surveillance and assisting with molecular genetic analyses, but evidence was generally weaker or only reported on what was done, without validation data or findings related to effectiveness of recency assays when used for these purposes.

Conclusions

HIV recency assays have been widely validated for estimating HIV incidence in age- and sex-specific populations at national and sub-national regional levels; however, there was a lack of evidence validating the accuracy and effectiveness of using recency assays for non-incidence surveillance use cases. The evidence identified through this review will be used in forthcoming technical guidance on the use of HIV recency assays for surveillance use cases by WHO and UNAIDS; further evidence on methodologies and effectiveness of non-incidence use cases is needed.
Intestinal function and transit associate with gut microbiota dysbiosis in cystic fibrosis
Authors: Marsh Ryan , Gavillet Helen , Hanson Liam , Ng Christabella , Mitchell-Whyte Mandisa , Major Giles , Smyth Alan R , Rivett Damian , van der Gast Christopher
Published: August 2021

Background

Most people with cystic fibrosis (pwCF) suffer from gastrointestinal symptoms and are at risk of gut complications. Gut microbiota dysbiosis is apparent within the CF population across all age groups, with evidence linking dysbiosis to intestinal inflammation and other markers of health. This pilot study aimed to investigate the potential relationships between the gut microbiota and gastrointestinal physiology, transit, and health.

Study Design

Faecal samples from 10 pwCF and matched controls were subject to 16S rRNA sequencing. Results were combined with clinical metadata and MRI metrics of gut function to investigate relationships.

Results

pwCF had significantly reduced microbiota diversity compared to controls. Microbiota compositions were significantly different, suggesting remodelling of core and rarer satellite taxa in CF. Dissimilarity between groups was driven by a variety of taxa, including Escherichia coli, Bacteroides spp., Clostridium spp., and Faecalibacterium prausnitzii. The core taxa were explained primarily by CF disease, whilst the satellite taxa were associated with pulmonary antibiotic usage, CF disease, and gut function metrics. Species-specific ordination biplots revealed relationships between taxa and the clinical or MRI-based variables observed.

Conclusions

Alterations in gut function and transit resultant of CF disease are associated with the gut microbiota composition, notably the satellite taxa. Delayed transit in the small intestine might allow for the expansion of satellite taxa resulting in potential downstream consequences for core community function in the colon.

Highlights

Faecal microbiota significantly differs between pwCF and healthy controls

Key SCFA producers contributed to microbiota dissimilarity between groups

Pulmonary antibiotic treatment heavily impacted gut microbiota

Intestinal physiology and transit impacted satellite microbiota composition
Enhanced neutrophil extracellular trap formation in COVID-19 is inhibited by the PKC inhibitor ruboxistaurin
Authors: Dowey Rebecca , Cole Joby , Thompson A A Roger , Huang Chenghao , Whatmore Jacob , Iqbal Ahmed , Bradley Kirsty L , McKenzie Joanne , Hull Rebecca C , Lawrie Allan , Condliffe Alison M , Kiss-Toth Endre , Sabroe Ian , Prince Lynne R
Published: August 2021

Neutrophil extracellular traps (NETs) are web-like DNA and protein lattices which are expelled by neutrophils to trap and kill pathogens, but which cause significant damage to the host tissue. NETs have emerged as critical mediators of lung damage, inflammation and thrombosis in COVID-19 and other diseases, but there are no therapeutics to prevent or reduce NETs that are available to patients. Here, we show that neutrophils isolated from hospitalised patients with COVID-19 produce significantly more NETs in response to LPS compared to cells from healthy control subjects. A subset of patients were captured at follow-up clinics (3-4 month post-infection) and while LPS-induced NET formation is significantly lower at this time point, it remains elevated compared to healthy controls. LPS- and PMA-induced NETs were significantly inhibited by the protein kinase C (PKC) inhibitor ruboxistaurin. Ruboxistaurin-mediated inhibition of NETs in healthy neutrophils reduces NET-induced epithelial cell death. Our findings suggest ruboxistaurin could reduce proinflammatory and tissue-damaging consequences of neutrophils during disease, and since it has completed phase III trials for other indications without safety concerns, it is a promising and novel therapeutic strategy for COVID-19.
Monitoring socioeconomic inequalities across HIV knowledge, attitudes, behaviours and prevention in 18 sub-Saharan African countries
Authors: Hamidouche Mohamed , Ante-Testard Pearl Anne , Baggaley Rachel , Temime Laura , Jean Kévin
Published: August 2021

Objectives

Socioeconomic inequalities in HIV prevention services coverage constitute important barriers to global prevention targets, especially in sub-Saharan Africa (SSA). We aimed at monitoring these inequalities from population-based survey data in 18 SSA countries between 2010 and 2018.

Methods

We defined eight HIV indicators aimed at capturing uptake of HIV prevention services among adult participants. Country-specific wealth-related inequalities were measured using the Relative and Slope Index of Inequalities (RII and SII, respectively) and then pooled using random-effects meta-analyses. We compared inequalities between African regions using the Wilcoxon rank-sum test.

Results

The sample consisted of 358,591 participants (66% women). Despite variability between countries and indicators, the meta-analysis revealed significant levels of relative and absolute inequalities in 6 out of 8 indicators: HIV-related knowledge, positive attitudes toward people living with HIV (PLHIV), condom use at last sexual intercourse, participation to prevention of mother-to-child transmission programs, medical male circumcision and recent HIV testing. The largest inequalities were reported in condom use, with condom use reported 5 times more among the richest versus the poorest (RII=5.02, 95% Confidence interval, CI: 2.79-9.05) and in positive attitudes toward PLHIV, with a 32-percentage point difference between the richest and poorest (SII=0.32, 95% CI: 0.26-0.39). Conversely, no significant inequalities were observed in multi-partnership and HIV seropositivity among youth. Overall, inequalities tended to be larger in West and Central vs. East and Southern African countries.

Conclusions

Despite efforts to scale-up HIV-prevention programs, socioeconomic inequalities remain substantial over the continuum of HIV primary and secondary prevention in several SSA countries.
Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients
Authors: Kaur Gagandeep , Maremanda Krishna P , Campos Michael , Chand Hitendra S , Li Feng , Hirani Nikhil , Haseeb M.A. , Rahman Irfan
Published: August 2021

Background

Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts.

Results

Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and ∼2.95 × 1010 particles/mL. Lung-derived exosomes were ∼146.04 nm in size and ∼2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls.

Conclusions

Overall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.
Inherited basis of visceral, abdominal subcutaneous and gluteofemoral fat depots
Authors: Agrawal Saaket , Wang Minxian , Klarqvist Marcus D. R. , Shin Joseph , Dashti Hesam , Diamant Nathaniel , Choi Seung Hoan , Jurgens Sean J. , Ellinor Patrick T. , Philippakis Anthony , Ng Kenney , Claussnitzer Melina , Batra Puneet , Khera Amit V.
Published: August 2021

For any given level of overall adiposity – as commonly quantified by body mass index (BMI) within clinical practice – individuals vary considerably in fat distribution. We and others have noted that increased visceral fat (VAT) is associated with increased cardiometabolic risk, while gluteofemoral fat (GFAT) may be protective. Familial partial lipodystrophy (FPLD) – often caused by rare variants in the LMNA gene – represents an extreme example of this paradigm, leading to a severe shift to visceral fat with subsequent insulin resistance and adverse metabolic profile. By contrast, the inherited basis of body fat distribution in the broader population is not fully understood. Here, we studied up to 38,965 UK Biobank participants with VAT, abdominal subcutaneous (ASAT), and GFAT volumes precisely quantified using abdominal MRI. Because genetic associations with these raw depot volumes were largely driven by variants known to affect BMI, we next studied six phenotypes of local adiposity: VAT adjusted for BMI (VATadjBMI), ASATadjBMI, GFATadjBMI, VAT/ASAT, VAT/GFAT, and ASAT/GFAT. We identify 178 unique loci associated with at least one adiposity trait, including 29 newly-identified loci. Rare variant association studies extend prior evidence of association for PDE3B as an important modulator of fat distribution. Sex-specific analyses of local adiposity traits noted overall higher estimated heritability in females, increased effect sizes for identified loci, and 25 female-specific associations. Individuals in the extreme tails of fat distribution phenotypes were highly enriched for predisposing common variants, as quantified using polygenic scores. Taking GFATadjBMI as an example, individuals with extreme values were 3.8-fold (95%CI 2.8 to 5.2) more likely to have a polygenic score within the top 5% of the distribution. These results – using more precise and BMI-independent measures of local adiposity – confirm fat distribution as a highly heritable trait with important implications for cardiometabolic health outcomes.
The efficacy and safety of bamlanivimab treatment against COVID-19: A meta-analysis
Authors: Xiang Huai-rong , He Bei , Li Yun , Cheng Xuan , Zhang Qi-zhi , Peng Wen-xing
Published: August 2021

Background

Bamlanivimab is routinely used in the treatment of coronavirus disease 2019 (COVID-19) in worldwide. We performed a meta-analysis to investigate the efficacy and safety of bamlanivimab treatment in patients with COVID-19.

Methods

We searched articles from Web of Science, PubMed, Embase, the Cochrane Library and MedRxiv between 30 January 2020 and August 5, 2021. We selected randomized clinical trials (RCTs) and observational studies with a control group to assess the efficiency of bamlanivimab in treating patients with COVID-19.

Results

Our meta-analysis retrieved 3 RCTs and 7 cohort studies including 14461 patients. Bmlanivimab may help outpatients to prevent hospitalization or emergency department visit (RR 0.41 95%CI 0.29 to 0.58), reduce ICU admission (RR 0.47 95%CI 0.23 to 0.92) and mortality (RR 0.32 95%CI 0.13 to 0.77) from the disease. The combination of bamlanivimab and etesevimab may had a greater potential for positive treatment outcome.

Conclusion

Bamlanivimab has demonstrated clinical efficacy on mild or moderate ill patients with COVID-19 to prevent hospitalization, reduce severity and mortality from the disease. Combinations of two or more monoclonal antibody increase the effect. Well-designed clinical trials to identify the clinical and biochemical characteristics in COVID-19 patients’ population that could benefit from bamlanivimab are warranted in the future.

Key points

Question

Can bamlanivimab treat COVID-19 patients? What are the factors that have great impact on the treatment outcome?

Findings

In this meta-analysis that retrieved 3 RCTs and 7 cohort studies and included 14461 adults, Bmlanivimab may help outpatients to prevent hospitalization or emergency department visit (RR 0.41 95%CI 0.29 to 0.58), reduce ICU admission (RR 0.47 95%CI 0.23 to 0.92) and mortality (RR 0.32 95%CI 0.13 to 0.77) from the disease.

Meaning

In COVID-19 pandemic, the use of bamlanivimab may be warranted. Combinations of two or more monoclonal antibody increase the effect.
Long-term precision editing of neural circuits in mammals using engineered gap junction hemichannels
Authors: Ransey Elizabeth , Chesnov Kirill , Thomas Gwenaëlle E. , Wisdom Elias , Almoril-Porras Agustin , Bowman Ryan , Rodriguez Tatiana , Adamson Elise , Walder-Christensen Kathryn K. , Hughes Dalton , Schwennesen Hannah , Mague Stephen D. , Colón-Ramos Daniel , Hultman Rainbo , Bursac Nenad , Dzirasa Kafui
Published: August 2021

The coordination of activity between brain cells is a key determinant of neural circuit function; nevertheless, approaches that selectively regulate communication between two distinct cellular components of a mammalian circuit remain sparse. To address this gap, we developed a novel class of gap junctions by selectively engineering two connexin proteins found inMorone americana(white perch fish): connexin34.7 (Cx34.7) and connexin35 (Cx35). By iteratively exploiting protein mutagenesis, a novelin vitroassay of connexin docking, and computational modeling of connexin hemichannel interactions, we uncovered a pattern of structural motifs that contribute to hemichannel docking compatibility. Targeting these motifs, we designed Cx34.7 and Cx35 hemichannels that dock with each other, but not with themselves, nor with other major connexins expressed in the mammalian central nervous system. We validated these hemichannelsin vivousingC. elegansand mice, demonstrating that they can facilitate communication across neural circuits composed of pairs of distinct cell types and modify behavior accordingly. Thus, we establish a potentially translational approach, ‘Long-termintegration ofCircuits using connexins’ (LinCx), for context-precise circuit-editing with unprecedented spatiotemporal specificity in mammals.
Genome-wide characterization of the R2R3-MYB transcription factors in pepper (Capsicum spp.) unveils the role of CaMYB101 as repressor in anthocyanin biosynthesis
Authors: Liu Ying , Wu Yi , Wang Zicheng , Zhang Shiya , Liu Xintong , Tikunov Yury , Visser Richard G.F. , Schouten Rob E. , Marcelis Leo F.M. , Zhang Zhao , Bovy Arnaud
Published: August 2021

Fruit colour is one of the most important commercial traits of pepper (Capsicum spp.), a major horticultural crop worldwide. Some pepper accessions temporarily accumulate anthocyanins during fruit development and gradually lose them upon fruit ripening. Meanwhile, anthocyanin biosynthesis gradually stops. However, how this process is exactly regulated is still largely unknown. R2R3-MYB is one of the largest plant transcription factor families, and it is considered the most important regulator for the biosynthesis of anthocyanins and other flavonoids. Although R2R3-MYBs are widely studied in many plants, research in pepper has been limited. In this study, we performed a genome-wide analysis of R2R3-MYBs across three cultivated pepper species (C. annuum, C. baccatum, and C. chinense ) involving identification, chromosome localization, gene structure analysis, phylogenetic analysis and collinearity analysis. Candidate R2R3-MYB repressors were further identified based on repression motifs. An R2R3-MYB gene, CaMYB101, was selected based on its high homology with anthocyanin biosynthesis repressors in tomato and petunia as well as its high expression level in fruit when purple pigmentation started to discolour. By using virus-induced gene silencing, CaMYB101 was characterized as an anthocyanin biosynthesis repressor. To our knowledge, CaMYB101 is the first transcriptional repressor associated with anthocyanin biosynthesis identified in pepper.
Top-down, knowledge-based genetic reduction of yeast central carbon metabolism
Authors: Postma Eline D. , Couwenberg Lucas G.F. , van Roosmalen Roderick N. , Geelhoed Jordi , de Groot Philip A. , Daran-Lapujade Pascale
Published: August 2021

Saccharomyces cerevisiae, whose evolutionary past includes a whole-genome duplication event, is characterised by a mosaic genome configuration with substantial apparent genetic redundancy. This apparent redundancy raises questions about the evolutionary driving force for genomic fixation of ‘minor’ paralogs and complicates modular and combinatorial metabolic engineering strategies. While isoenzymes might be important in specific environments, they could be dispensable in controlled laboratory or industrial contexts. The present study explores the extent to which the genetic complexity of the central carbon metabolism (CCM) in S. cerevisiae, here defined as the combination of glycolysis, pentose phosphate pathway, tricarboxylic acid cycle and a limited number of related pathways and reactions, can be reduced by elimination of (iso)enzymes without major negative impacts on strain physiology. Cas9-mediated, groupwise deletion of 35 from the 111 genes yielded a ‘minimal CCM’ strain, which despite the elimination of 32 % of CCM-related proteins, showed only a minimal change in phenotype on glucose-containing synthetic medium in controlled bioreactor cultures relative to a congenic reference strain. Analysis under a wide range of other growth and stress conditions revealed remarkably few phenotypic changes of the reduction of genetic complexity. Still, a well-documented context-dependent role of GPD1 in osmotolerance was confirmed. The minimal CCM strain provides a model system for further research into genetic redundancy of yeast genes and a platform for strategies aimed at large-scale, combinatorial remodelling of yeast CCM.