bluuebunny/crossref_metadata_2025 huggingface dataset:
A pragmatic reevaluation of the efficacy of nonhuman primate optogenetics for psychiatry
Authors: Bliss-Moreau Eliza , Costa Vincent D , Baxter Mark G
Published: May 2022

Translational neuroscience is committed to generating discoveries in the laboratory that ultimately can improve human lives. Optogenetics has received considerable attention because of its demonstrated promise in rodent brains to manipulate cells and circuits. In a recent report, Tremblay et al. [28] introduce an open resource detailing optogenetic studies of the nonhuman primate (NHP) brain and make robust claims about the translatability of the technology. We propose that their quantitative (e.g. a 91% success rate) and theoretical claims are questionable because the data were analyzed at a level relevant to the rodent but not NHP brain. Injections were clustered within a few monkeys in a few studies in a few brain regions, and their definitions of success were not clearly relevant to human neuropsychiatric disease. A reanalysis of the data with a modified definition of success that included a behavioral and biological effect revealed a 62.5% success rate that was lower when considering only strong outcomes (53.1%). This calls into question the current efficacy of optogenetic techniques in the NHP brain and suggests that we are a long way from being able to leverage them in ‘the service of patients with neurological or psychiatric conditions’ as the Tremblay report claims.
Dramatic effects of COVID-19 public health measures and mass reverse migration on youth sexual and reproductive health in rural Uganda
Authors: Khan Sundus , Kemigisha Elizabeth , Turyakira Eleanor , Chaput Kathleen , Kabakyenga Jerome , Kyomuhangi Teddy , Manalili Kimberly , Brenner Jennifer L
Published: May 2022

Introduction

Youth (aged 10 to 24 years) comprise nearly one-third of Uganda’s population and often face challenges accessing sexual and reproductive health (SRH) services, with a disproportionately high incidence of negative SRH outcomes. Responding to COVID-19, Uganda implemented strict public health measures including broad public transportation, schooling, and business shut-downs, causing mass reverse-migration of youth from urban schools and workplaces back to rural home villages. Our study aimed to qualitatively describe the perceived unintended impacts of COVID-19 health measures on youth SRH in two rural districts.

Methods

Semi-structured focus group discussions (FGD) and key informant interviews (KII) with purposively selected youth, parents, community leaders, community health worker (CHW) coordinators and supervisors, health providers, facility and district health managers, and district health officers were conducted to explore lived experiences and impressions of the impacts of COVID-19 measures on youth SRH. Interviews were recorded, transcribed, and coded using deductive thematic analysis.

Results

Four COVID-19-related themes and three subthemes resulted from 15 FGDs and 2 KIIs (n=94). Public transportation shutdown and mandatory mask-wearing were barriers to youth SRH care-seeking. School/workplace closures and subsequent urban youth migration back to rural homes increased demand at ill-prepared, rural health facilities, further impeding care-seeking. Youth reported fear of discovery by parents, which deterred SRH service seeking. Lockdown led to family financial hardship, isolation, and overcrowding; youth mistreatment, gender-based violence, and forced marriage ensued with some youth reportedly entering partnerships as a means of escape. Idleness and increased social contact were perceived to lead to increased and earlier sexual activity. Reported SRH impacts included increased severity of infection and complications due to delayed care seeking, and surges in youth sexually transmitted infections, pregnancy, and abortion.

Conclusion

COVID-19 public health measures reportedly reduced youth care seeking while increasing risky behaviours and negative SRH outcomes. Investment in youth SRH programming is critical to reverse unintended pandemic effects and regain momentum toward youth SRH targets. Future pandemic management must consider social and health disparities, and mitigate unintended risks of public health measures to youth SRH.
Cross-species metabolomic analysis of tau- and DDT-related toxicity
Authors: Kalia Vrinda , Niedzwiecki Megan M , Bradner Joshua M , Lau Fion K , Anderson Faith L , Bucher Meghan L , Manz Katherine E , Schlotter Alexa Puri , Fuentes Zoe Coates , Pennell Kurt D , Picard Martin , Walker Douglas I , Hu William T , Jones Dean P , Miller Gary W
Published: May 2022

Exposure to the pesticide dichlorodiphenyltrichloroethane (DDT) has been associated with increased risk of Alzheimer's disease (AD), a disease also associated with hyperphosphorylated tau (p-tau) protein aggregation. We investigated whether exposure to DDT can exacerbate tau protein toxicity in Caenorhabditiselegans using a transgenic strain that expresses human tau protein prone to aggregation by measuring changes in size, swim behavior, respiration, lifespan, learning, and metabolism. In addition, we examined the association between cerebrospinal fluid (CSF) p-tau protein—as a marker of postmortem tau burden—and global metabolism in both a human population study and in C. elegans, using the same p-tau transgenic strain. From the human population study, plasma and CSF-derived metabolic features associated with p-tau levels were related to drug, amino acid, fatty acid, and mitochondrial metabolism pathways. A total of five metabolites overlapped between plasma and C. elegans, and four between CSF and C. elegans. DDT exacerbated the inhibitory effect of p-tau protein on growth and basal respiration. In the presence of p-tau protein, DDT induced more curling and was associated with reduced levels of amino acids but increased levels of uric acid and adenosylselenohomocysteine. Our findings in C. elegans indicate that DDT exposure and p-tau aggregation both inhibit mitochondrial function and DDT exposure can exacerbate the mitochondrial inhibitory effects of p-tau aggregation. Further, biological pathways associated with exposure to DDT and p-tau protein appear to be conserved between species.
Sleep pattern in the dromedary camel: a behavioral and polysomnography study
Authors: El Allali Khalid , Beniaich Younes , Farsi Hicham , M′hani Mohammed El Mehdi , Jabal Mohamed Sobhi , Piro Mohammed , Achaâban Mohamed Rachid , Ouassat Mohammed , Challet Etienne , Besson Mireille , Mounach Jamal , Pévet Paul , Satté Amal
Published: May 2022

Study Objectives

To investigate sleep patterns in the camel by combining behavioral and polysomnography (PSG) methods.

Methods

A noninvasive PSG study was conducted over four nights on four animals. Additionally, video recordings were used to monitor the sleep behaviors associated with different vigilance states.

Results

During the night, short periods of sporadic sleep-like behavior corresponding to a specific posture, sternal recumbency (SR) with the head lying down on the ground, were observed. The PSG results showed rapid shifts between five vigilance states, including wakefulness, drowsiness, rapid eye movement (REM) sleep, non-REM (NREM) sleep, and rumination. The camels typically slept only 1.7 hours per night, subdivided into 0.5 hours of REM sleep and 1.2 hours of NREM sleep. Camels spent most of the night being awake (2.3 hours), ruminating (2.4 hours), or drowsing (1.9 hours). Various combinations of transitions between the different vigilance states were observed, with a notable transition into REM sleep directly from drowsiness (9%) or wakefulness (4%). Behavioral postures were found to correlate with PSG vigilance states, thereby allowing a reliable prediction of the sleep stage based on SR and the head position (erected, motionless, or lying down on the ground). Notably, 100% of REM sleep occurred during the Head Lying Down-SR posture.

Conclusions

The camel is a diurnal species with a polyphasic sleep pattern at night. The best correlation between PSG and ethogram data indicates that sleep duration can be predicted by the behavioral method, provided that drowsiness is considered a part of sleep.
Forced heirship and Jersey trusts—the Islamic perspective
Authors: Chien Nancy , Carter Lydia
Published: May 2022

Sharia law is very specific about how a deceased person’s estate is to be divided between their close relatives. For those of Islamic faith who wish to have more freedom in these cases where there is difficulty in freely passing wealth down to family members, the concept known as “forced heirship”, Jersey trusts law may provide one solution. Under Jersey trusts law, the settlor has complete freedom over how the property is to be held and who should benefit from the trust. Article 9 of the Trusts (Jersey) Law 1984 sets out that where a testator who would otherwise be subject to forced heirship provisions settles property on a Jersey law trust, all matters in respect of the trust shall be determined by Jersey law, even if there is another conflicting law at play. Article 9 also provides that no judgment of a foreign court will be given effect to the extent that it is inconsistent with Article 9. Jersey’s firewalls have not been tested specifically with regard to Sharia law forced heirship claims. However, they have been shown to be robust in respect of other foreign law claims. There are some practical constraints which could weaken the protection afforded by Article 9, e.g. where the assets are not located in Jersey so that a foreign court would have jurisdictional reach over the assets. As such, one should consider carefully how to draft the trust documents in order to mitigate such risks.
Decreasing susceptibility of bacteria to ampicillin/ sulbactam and third generation cephalosporins in urinary tract infections
Authors: Vallo Stefan , Wirth Patrick , Kukic Adnan , Nafez Omar , Neagoe Ladislau , Nestler Sebastian , Jones Jon
Published: May 2022

Background:

Urinary tract infections (UTIs) are among the most common bacterial infections worldwide and have become more difficult to treat over the years. Inappropriate antibiotic use has led to increased antibiotic resistance.

Materials and methods:

We examined 1921 urine culture samples from a single hospital and analyzed them for bacterial spectrum and antibiotic susceptibility. We further analyzed changes in the rates of detected bacteria and of the sensitivity of these uropathogens to antibiotics over the years.

Results:

In our hospital-based analysis, cystitis was the most frequently diagnosed UTI in women (76%) and men (79%). Escherichia coli (48%) was the most commonly identified uropathogen. Samples demonstrated an increase in the proportion of E. coli (p 
< 0.001) and a decrease in Enterococcus faecalis (p 
< 0.001) over the study time period. Antimicrobial susceptibility analysis showed an increase over time in the number of isolates with resistance to ampicillin/sulbactam (p 
< 0.001) and to third-generation cephalosporins cefotaxime (p 
= 0.043) and ceftazidime (p 
< 0.001).

Conclusions:

Ampicillin/sulbactam and third-generation cephalosporins are antibiotics frequently used in the treatment of UTIs. When selecting an optimal antimicrobial treatment regimen for patients with UTIs, it is imperative to understand regional and timedependent differences in the prevalence of various uropathogens and antimicrobial resistance patterns. Therefore, continuous surveillance of local pathogen and antimicrobial susceptibility patterns for frequently used antibiotics should be prioritized.
ONE-YEAR OUTCOMES OF METAMORPHOPSIA AND RETINAL DISPLACEMENT AFTER EPIRETINAL MEMBRANE SURGERY
Authors: Watanabe Amaka , Ishida Masahiro , Shibata Masaki , Fujimoto Taichi , Mizushima Akio , Takeyama Asuka , Imamura Yutaka
Published: May 2022

Purpose:

To examine 1-year outcomes of metamorphopsia and tangential retinal displacement after epiretinal membrane surgery and identify predictors for metamorphopsia score at 1 year and its improvement from baseline.

Methods:

M-CHARTS were used to measure metamorphopsia. Distances between the intersections of two sets of retinal vessels were measured with infrared or autofluorescence images. Predictors for metamorphopsia scores at 1 year after surgery and their differences from baseline were identified with multivariate regression analysis.

Results:

Ninety-two eyes of 90 consecutive patients were included. The vertical and horizontal distances continued expanding for 1 year (P < 0.001). Both vertical and horizontal metamorphopsia scores improved 3 months after surgery (P = 0.025 and P < 0.001, respectively), and horizontal scores continued improving for a year. Horizontal metamorphopsia scores correlated with retinal displacement more strongly than vertical scores. Higher metamorphopsia score at baseline is predictive for that at 1 year. Older age and being male are predictive for less improvement of the score at 1 year from baseline.

Conclusion:

Metamorphopsia correlates with tangential retinal displacement at 1 year after epiretinal membrane surgery. Horizontal metamorphopsia scores keep improving until 1 year postoperatively. Being male and older age are both independent predictors for poor improvement of metamorphopsia after epiretinal membrane surgery.
Clinical efficacy of high-intensity laser therapy (HILT) on lateral epicondylitis patients: A systematic review and meta-analysis
Authors: ElMeligie Mohamed Magdy , Gbreel Mohamed Ibrahim , Yehia Radwa Mohamed , Hanafy Abeer Farag
Published: May 2022

Objectives

Recently, high-intensity laser therapy (HILT) has been used in the therapeutic protocols for pain management. We aim to evaluate the clinical efficacy of HILT versus other different modalities for improving lateral epicondylitis (LE) symptoms.

Methodology

We conducted a systematic review and meta-analysis on prospective randomized controlled trials (RCTs) from PubMed, Embase, Scopus, Web of Science (WOS), and Science Direct till June 2021 using relevant keywords. We analyzed the data using Review Manager software (RevMan 5.4).

Results

Six RCTs with 344 patients were included. There is low-quality evidence that HILT generates a small reduction on pain intensity compared to a control group either during activity (MD = -0.98, 95% CI -1.6 to -0.35, P = 0.002) or during rest (MD = -0.98, 95% CI -1.68 to -0.09, P = 0.03). Also, there is low-quality evidence that HILT provides small improvements in quality of life (physical component) compared to control (MD = 9.76; 95% CI 2.69 to16.83, P < 0.0001).

Conclusion

HILT is an effective therapeutic modality to reduce pain and improve quality of life (SF-36 physical component) in patients suffering from persistent symptoms of LE. However, grip strength, hand function, and quality of life (SF-36) did not show significant differences between HILT and other therapies.
Effects of Patient Suicide on Professional Practice Among Mental Health Providers
Authors: Spruch-Feiner Aliza , Labouliere Christa D. , Brodsky Beth , Green Kelly L. , Brown Gregory K. , Vasan Prabu , Cummings Anni , Layman Deborah , Monahan Maureen F. , Galfalvy Hanga , Rahman Mahfuza , Kammer Jamie , Wainberg Milton L. , Nicholson Terriann , Leckman-Westin Emily , Finnerty Molly , Stanley Barbara
Published: May 2022

Introduction:

The loss of a patient to suicide has an enormous impact on clinicians, but few studies have examined its effects.

Method:

In this retrospective study, we compared clinicians who have and have not experienced a patient suicide using a survey of 2157 outpatient clinicians from 169 New York clinics to determine differences in their suicide prevention knowledge, practices, training, and self-efficacy.

Results:

Approximately 25% of the clinician respondents lost patients to suicide; psychiatrists, nurses/nurse practitioners, and those with more years of experience were disproportionately affected. After controlling for these demographic/professional differences, clinicians who had experienced patient suicide reported feeling that they had insufficient training, despite actually having more suicide prevention training, greater knowledge of suicide prevention practices, and feeling more comfortable working with suicidal patients than clinicians who had not lost a patient to suicide. There were no differences in self-efficacy or utilization of evidence-based clinical practices.

Conclusions:

Controlling for demographic/professional differences, clinicians who experienced a patient suicide had more training, knowledge, and felt more comfortable working with suicidal patients. It is critical that sufficient training be available to clinicians, not only to reduce patient deaths, but also to help clinicians increase their comfort, knowledge, skill, and ability to support those bereaved by suicide loss.
Fresh Frozen Rib Cartilage Grafts in Revision Rhinoplasty: A 9-Year Experience
Authors: Rohrich Rod J. , Abraham Jasson , Alleyne Brendan , Bellamy Justin , Mohan Raja
Published: May 2022

Background:

Revision rhinoplasty is undoubtedly one of the most challenging procedures in facial plastic surgery. The complexity is compounded when there is a paucity of native septal cartilage to perform the required framework reconstruction. Harvest of autologous costal cartilage can result in increased operative times and possible secondary-site complications such as contour irregularity, poor scarring, and even pneumothorax.

Methods:

A retrospective review was conducted of the senior author’s (R.J.R.) patients from 2011 to 2020 who underwent primary or revision rhinoplasty. Inclusion criteria consisted of patients with fresh frozen off-the-shelf cartilage used in revision rhinoplasty only with a minimum of 6 months’ follow-up. Outcomes for evaluation were warping, resorption, displacement, and infection.

Results:

The authors identified 226 patients who underwent open rhinoplasty with the use of fresh frozen rib cartilage grafts and met inclusion criteria. The mean follow-up period was 12.18 months (range, 6 months to 8 years). The majority of patients had undergone one prior rhinoplasty procedure (54 percent); however, 4 percent of patients had undergone four or more prior procedures on their nose. The overall infection rate was 2.7 percent (n = 6), with the majority successfully managed with antibiotics alone (2.3 percent).

Conclusions:

The results in revision rhinoplasty are significantly enhanced with the creation of a stable nasal framework using off-the-shelf, easily accessible, specifically tailored fresh frozen cadaveric rib grafts. The long-term outcomes and complication rate in this 9-year retrospective study demonstrates the safety of fresh frozen rib graft in comparison to autologous or irradiated rib graft.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Actual prosthetic usage in relation to functional outcomes and wearing time in individuals with below-elbow amputation
Authors: Salminger Stefan , Gstoettner Clemens , Sturma Agnes , Mayer Johannes A , Papst Helmut , Aszmann Oskar C
Published: May 2022

Background:

Wearing time of a prosthesis is regarded as an indicator for success of prosthetic rehabilitation. However, prostheses are frequently worn for esthetic purposes only. Although different supervised measurements to assess prosthetic dexterity are used, it is not clear how performance in such tests translates into actual use in everyday life.

Objectives:

To evaluate the actual daily use of the prosthetic device in patients with below-elbow amputations by recording the number of grasping motions.

Study design:

Observational study.

Methods:

Upper extremity function was evaluated using different objective and timed assessments in five unilateral patients with below-elbow amputations. In addition, patients reported daily wearing time, and the number of performed prosthetic movements over a period of at least three months was recorded.

Results:

The patients achieved a mean Southampton Hand Assessment Procedure score of 66.60 ± 18.64 points. The average blocks moved in the Box and Block Test were 20.80 ± 7.46, and the mean score in the Action Research Arm Test was 37.20 ± 5.45. The mean time for the Clothespin-Relocation Test was 26.90 ± 11.61 seconds. The patients reported a wearing time of an average of 12.80 ± 3.11 hours per day. The mean number of prosthetic motions performed each day was 257.23 ± 192.95 with a range from 23.07 to 489.13.

Conclusions:

Neither high functionality nor long wearing times necessitated frequent use of a prosthesis in daily life. However, frequent daily motions did translate into good functional scores, indicating that regular device use in different real-life settings relates to functionality.
Using theoretical frameworks to examine fall history and associated prosthetic mobility in people with nondysvascular lower limb amputation
Authors: Clemens Sheila , Gaunaurd Ignacio , Raya Michele , Kirk-Sanchez Neva , Klute Glenn , Gailey Robert
Published: May 2022

Background:

Over a million people live with lower limb amputation (LLA) in the United States, and many of them will experience a fall in the next year. The aim of this study was to use existing theoretical frameworks in an attempt to organize the complex interactions of reported fall history and prosthetic mobility in community-ambulating people with LLA.

Methods:

Self-reported fall rate and fall circumstances were recorded in a cross-section of people with unilateral LLA due to nondysvascular causes. Self-report and performance-based standardized outcome measures assessed prosthetic mobility and balance confidence. All variables were considered and appropriately placed within a proposed International Classification of Functioning, Disability, and Health framework while using a fall-type classification framework to classify fall circumstances.

Results:

Information from 69 participants was analyzed. The reported fall rate was at 46%, with those with transfemoral amputation reporting significantly more falls than those with transtibial amputation (P = 0.001). Tripping over an object was the most common cause (62.5%), and fallers reported significantly lower perceived prosthetic mobility than nonfallers (P = 0.001). Despite reporting high levels of balance confidence, results indicate that all groups of fallers and nonfallers are at increased fall risk according to performance-based prosthetic mobility score cutoffs.

Conclusions:

Community-dwelling people with nondysvascular LLA are at increased fall risk. Classifying fall-related variables using theoretical frameworks provides a means to structure more informative fall risk surveys for people with LLA in an attempt to identify those at greater risk for falling and its potential detrimental effects.
Magnetoencephalography Language Mapping Using Auditory Memory Retrieval and Silent Repeating Task
Authors: Ji Zhengwei , Song Ryan R. , Swan Ashley Robb , Angeles Quinto Annemarie , Lee Roland R. , Huang Mingxiong
Published: May 2022

Purpose:

The study aims to (1) examine the spatiotemporal map of magnetoencephalography-evoked responses during an Auditory Memory Retrieval and Silent Repeating (AMRSR) task, and determine the hemispheric dominance for language, and (2) evaluate the accuracy of the AMRSR task in Wernicke and Broca area localization.

Methods:

In 30 patients with brain tumors and/or epilepsies, the AMRSR task was used to evoke magnetoencephalography responses. We applied Fast VEctor-based Spatial–Temporal Analyses with minimum L1-norm source imaging method to the magnetoencephalography responses for localizing the brain areas evoked by the AMRSR task.

Results:

The Fast-VEctor-based Spatial–Temporal Analysis found consistent activation in the posterior superior temporal gyrus around 300 to 500 ms, and another activation in the frontal cortex (pars opercularis and/or pars triangularis) around 600 to 900 ms, which were localized to the Wernicke area (BA 22) and Broca area (BA 44 and BA 45), respectively. The language-dominant hemispheric laterization elicited by the AMRSR task was comparable with the result from an Auditory Dichotic task result given to the same patient, with the exception that AMRSR is more sensitive on bilateral language laterization cases on finding the Wernicke and Broca areas.

Conclusions:

For all patients who successfully finished the AMRSR task, Fast-VEctor-based Spatial–Temporal Analysis could establish accurate and robust localizations of Broca and Wernicke area and determine hemispheric dominance. For subjects with normal auditory functionality, the AMRSR paradigm evaluation showed significant promise in providing reliable assessments of cerebral language dominance and language network localization.
Heme Oxygenase-1 Promoter (GT)n Alleles and Neurocognitive Functioning in Thai Youth with Perinatally-Acquired HIV: A Pilot Study
Authors: Santoro Anthony F. , Aurpibul Linda , Kolson Dennis , Ferraris Christopher M. , Aghvinian Maral , Garcia-Mesa Yoelvis , Lui Jun , Dirajlal-Fargo Sahera , Robbins Reuben N.
Published: May 2022

Background

Heme oxygenase-1 (HO-1) gene promoter (GT)n dinucleotide repeat length variations may modify HIV-associated neurocognitive impairment (HIV-NCI) risk. Among adults, short HO-1 (GT)n alleles associate with greater HO-1 antioxidant enzyme inducibility and lower rates of HIV-NCI. This pilot study examined associations between HO-1 (GT)n alleles and neurocognitive outcomes in a sample of Thai youth (13-23 years) with perinatally-acquired HIV (PHIV) and demographically-matched HIV-negative controls.

Methods

Participants completed neurocognitive testing and provided blood samples for DNA extraction and sequencing of HO-1 promoter (GT)n dinucleotide repeat lengths. Allele lengths were assigned based on number of (GT)n repeats: <27 Short (S); 27-34 Medium (M); >34 Long (L). Relationships between HO-1 (GT)n repeat lengths and neurocognitive measures were examined, and differences by HO-1 (GT)n allele genotypes were explored.

Results

Nearly half (48%) of all HO-1 (GT)n promoter alleles were short. Longer repeat length of participants’ longest HO-1 (GT)n alleles significantly associated with poorer processing speed (Total sample:r=-.36,p=.01; PHIV only:r=-.69,p<.001). Compared to peers and controlling for covariates, SS/SM genotypes performed better in processing speed, and SS genotypes performed worse in working memory.

Conclusions

A high frequency of short HO-1 (GT)n alleles was found among these Thai youth, as previously observed in other cohorts of people of Asian ancestry. In contrast to previous adult studies, the presence of a short allele alone did not associate with better neurocognitive performance, suggesting additional modifying effects among the different alleles. Research is needed to determine whether HO-1 (GT)n promoter genotypes differentially influence neurocognitive functioning across the lifespan and different ethnic backgrounds.
Speed and accuracy of whole-genome nanopore sequencing for differential Neisseria gonorrhoeae strain detection in samples collected prospectively from a sexual health clinic
Authors: Phillips LT , Witney AA , Furegato M , Laing KG , Zhou L , Sadiq ST
Published: May 2022

Background

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a continuing global health challenge. Limitations to current national surveillance systems for reporting AMR trends, alongside reduction in culture-based diagnostics and susceptibility testing, has led to an increasing need for rapid diagnostics and identification of circulating N. gonorrhoeae strains. We investigated nanopore based sequencing time and depth needed to accurately identify closely related N. gonorrhoeae isolates, compared to Illumina MiSeq sequencing.

Methods

N. gonorrhoeae strains prospectively collected from a London Sexual Health clinic were sequenced on both Illumina MiSeq and Oxford Nanopore Technologies (ONT) MinION platforms. Accuracy was determined by comparing variant calls at 68 nucleotide positions representing 37 pre-characterised resistance associated markers in N. gonorrhoeae. Accuracy at varying MinION sequencing depths were determined through retrospective analysis of time-stamped reads.

Results

Of the 22 MinION-MiSeq sequence pairs that reached sufficient depth of coverage for comparison, overall agreement of variant call positions passing quality control criteria was 185/185 (95% CI: 98.0-100.0), 502/503 (95% CI: 98.9-99.9) and 564/565 (95% CI: 99.0-100.0) at 10x, 30x and 40x MinION depth, respectively. Isolates found to be genetically closely related by MiSeq, that is within one yearly evolutionary distance of ≤5 single nucleotide polymorphisms, were accurately identified as such via MinION.

Conclusion

Nanopore based sequencing shows utility for use as a rapid surveillance tool to correctly detect closely related N. gonorrhoeae strains, with just 10x sequencing depth, taking a median sequencing time of 29 minutes. This highlights its potential utility for tracking local gonorrhoea transmission and AMR markers.
WHO TARGETS FOR CERVICAL CANCER CONTROL BY 2030: A BASELINE ASSESSMENT IN SIX AFRICAN COUNTRIES
Authors: Stefan D Cristina , Dangou Jean-Marie , Barango Prebo , Mahamadou Issimouha Dille , Kapambwe Sharon
Published: May 2022

Aim

We present and analyze the findings of a survey of the readiness of the healthcare systems in Eswatini, Guinea, Malawi, Rwanda, Uganda and Zambia, to implement the necessary measures for attaining the targets for cervical cancer control, set by WHO, by the year 2030.

Methods

A questionnaire with 129 questions with preset answer options was completed in 2020, by ministries of health program coordinators for non-communicable diseases, cancer control and/or reproductive health, and by WHO country offices, in the six countries selected.

Results

The findings on demographics, burden of disease, governance and management, laboratory services, equipment, supplies and medicines, as well as on personnel and training will be presented here.

The burden of cervical cancer in the countries studied is considerable, based on the IARC estimations. The incidence of the disease is augmented by the high prevalence of HIV infection, in most of the countries surveyed. Most of the population live in rural areas, where access to the health services is far from ideal. Facilities for screening with HPV tests and for histopathology are limited. One pathologist covers the diagnostic needs of between 0.5 million and 4 million inhabitants. Most other categories of health professionals are under-represented, and the capacity to train them is inadequate.

Conclusions

Strong country commitment and leadership, innovative solutions and extensive international cooperation would be needed to attain the targets of cervical cancer control set by WHO, in these countries.
Effect of a 12-mo milk-based micronutrient-fortified drink intervention on children: a systemic analysis of placebo-controlled study dataset
Authors: Lomore Karan , Gangwar Vani , Rizvi Samreen , Venkatesh KV
Published: May 2022

Background

Nutritional deficiencies have many immediate and long-term effects on physical and cognitive development outcomes, with the children not achieving their full potential. A milk-based health drink fortified with micronutrients as a part of a daily balanced diet can promote physical and cognitive growth in children by increasing macronutrients and micronutrients availability in the body. The systematic analysis aims to quantify the effect of a formulated health drink on children’s physical, clinical, and cognitive development outcomes.

Methods

The dataset used in the analysis was obtained from literature and consisted of 900 children between 7 to 12 years of age. These children were distributed equally into the Control group (no micronutrient-fortified health drink is given), Group I (micronutrient-fortified health drink in water), and Group II (micronutrient-fortified health drink in the toned milk).

Results

The analysis shows that micronutrient-fortified health drinks in water (by 2.1-fold) and toned milk (by 2.5-fold) improve the height gain velocities and anthropometric and body composition parameters. It helped children achieve healthy IAP growth percentiles compared to the control group. The analysis also shows a 1.6- and 2-fold change in the cognitive tests grades in groups I & II, respectively, compared to the control group.

Conclusions

The analysis indicates that two servings of 33g micronutrient-fortified health drink in water and toned milk for a year significantly improved the gain velocities of anthropometric and body composition parameters, reduced time taken to complete the physical activity task, reduced the number of anaemia and morbidity cases among groups, and improved the scoring grades in cognitive assessment test in studied children population. The IAP data benchmarking clearly indicated that a micronutrient fortified milk-protein-based powder significantly improved children’s overall growth with better health.
Determinants of maternal morbidity during pregnancy in urban Bangladesh: Negative binomial regression approach
Authors: Hossain Zakir , Afroz Nilima , Sharmin Sabina , Sharmin Sayema , Kabir Enamul
Published: May 2022

Aim

To investigate the prevalence of maternal morbidity during pregnancy and its determinants among the women from urban areas of Bangladesh.

Methods

The secondary data were used and extracted from the latest Bangladesh Urban Health Survey (BUHS) 2013. Several statistical models: Poisson, negative binomial (NB) and mixed Poisson were adapted and compared to explore the best model for investigating potential determinants of maternal morbidity. Pearson chi-square statistic was used for the detection of overdispersion in the data.

Results

Overall 13.5% of the urban women in Bangladesh suffered from at least two pregnancy complications. The study detected the overdispersion existing in the maternal morbidity count data and found the NB regression as the best choice for analyzing the data because of its smallest Akaike information criterion. Administrative division (Rangpur:p=0.003, IRR=1.34, 95% CI: 1.11 to 1.63; Sylhet:p=0.006, IRR=1.42, 95% CI: 1.11 to 1.82), wanted pregnancy (p<0.001, IRR=0.80, 95% CI: 0.71 to 0.90), place of delivery (p<0.001, IRR=0.60, 95% CI: 0.54 to 0.66) and wealth index (Rich:p<0.001, IRR=0.74, 95% CI: 0.66 to 0.84) were found to be statistically significant determinants for maternal morbidity during pregnancy among the urban women in Bangladesh.

Conclusions

The urban women in Bangladesh with unwanted pregnancy, from poor/middle income group; and living in Rangpur and Sylhet divisional cities have higher risk of maternal morbidity during pregnancy. The women already suffering from major pregnancy related complications visit health centre to give birth. Study findings may help the government and relevant authorities to take necessary steps for reducing maternal morbidity and mortality due to pregnancy related complications.
The role of dynamic DNA methylation in liver transplant rejection in children
Authors: Ningappa Mylarappa , Shao Xiaojian , Ashokkumar Chethan , Xu Qingyong , Zeevi Adriana , Grundberg Elin , Pastinen Tomi , Sindhi Rakesh
Published: May 2022

Background

Transcriptional regulation of liver transplant (LT) rejection may reveal novel predictive and therapeutic targets.

Purpose

To test the role of differential DNA methylation in children with biopsy-proven acute cellular rejection (rejectors, R) after LT.

Methods

Paired peripheral blood DNA samples were obtained before and after LT from 17 children, including 4R and 13 non-rejector (NR), and assayed with MethylC capture sequencing (MCC-Seq) approach covering 5 million CpGs in immune-cell specific regulatory elements. Differentially methylated CpGs (DMCs) were identified using generalized linear regression models adjusting for sex and age and merged into differentially methylated regions (DMR) comprising 3 or more DMCs.

Results

Contrasting R vs NR, we identified 2238 DMCs in post-LT and 2620 DMCs in pre-LT samples, which clustered in 216 and 282 DMRs respectively. DMCs associated with R were enriched in enhancers and depleted in promoters. The proportion of hypomethylated versus hypermethylated DMRs increased from 22% to 48% (p<0.0001) in pre-LT vs. post-LT DMCs, respectively. The highest-ranked biological processes enriched in post-LT DMCs were antigen processing and presentation via MHC class I, MHC class I complex, and peptide binding (p<7.92E-17), respectively. Top-ranked DMRs mapped to genes which mediate B-cell receptor signaling (ADAP1) or regulate several immune cells(ARRB2)(p<3.75E-08). DMRs in MHC class I genes were enriched for SNPs which bind TFs, affect gene expression and splicing, or alter peptide-binding amino acid sequences.

Conclusions

Dynamic methylation in distal regulatory regions reveals known transplant-relevant MHC-dependent rejection pathways, and identifies novel loci for future mechanistic evaluations in pediatric transplant subcohorts.
N-terminal mutant Huntingtin deposition correlates with CAG repeat length and disease onset, but not neuronal loss in Huntington’s disease
Authors: Layburn Florence E. , Tan Adelie Y. S. , Mehrabi Nasim F. , Curtis Maurice A. , Tippett Lynette J. , Riguet Nathan , Aeschbach Lorène , Lashuel Hilal A. , Dragunow Mike , Faull Richard L. M. , Singh-Bains Malvindar K.
Published: May 2022

Huntington’s disease (HD) is caused by a CAG repeat expansion mutation in the gene encoding the huntingtin (Htt) protein, with mutant Htt protein subsequently forming aggregates within the brain. Mutant Htt is a current target for novel therapeutic strategies for HD, however, the lack of translation from preclinical research to disease-modifying treatments highlights the need to improve our understanding of the role of Htt protein in the human brain. This study aims to undertake a high-throughput screen of 12 candidate antibodies against various sequences along the Htt protein to characterize Htt distribution and expression in post-mortem human brain tissue microarrays (TMAs).

Immunohistochemistry was performed on middle temporal gyrus TMAs comprising of up to 28 HD and 27 age-matched control cases, using 12 antibodies specific to various sequences along the Htt protein. From this study, six antibodies directed to the Htt N-terminus successfully immunolabelled human brain tissue. The Htt aggregates and Htt protein expression levels for the six successful antibodies were subsequently quantified with high-throughput analysis. Htt aggregates were detected in HD cases using antibodies MAB5374, MW1, and EPR5526, despite no change in overall Htt protein expression compared to control cases, suggesting a redistribution of Htt into aggregates in HD. Significant associations were found between the number of Htt aggregates and both age of disease onset, and CAG repeat length in HD. However, the number of Htt aggregates did not correlate with the degree of striatal degeneration or the degree of cortical neuron loss. Together, these results suggest that longer CAG repeat lengths correlate with Htt aggregation in the HD human brain, and Htt cortical aggregate deposition is associated with the onset of clinical symptoms. This study also reinforces that antibodies MAB5492, MW8, and 2B7 which have been utilized to characterize Htt in animal models of HD are not specific for Htt in human brain tissue, thereby highlighting the need for validated means of Htt detection to support drug development for HD.
Genomic patterns of malignant peripheral nerve sheath tumour (MPNST) evolution correlate with clinical outcome and are detectable in cell-free DNA
Authors: Cortes-Ciriano I , Steele CD , Piculell K , Al-Ibraheemi A , Eulo V , Bui MM , Chatzipli A , Dickson BC , Borcherding DC , Feber A , Galor A , Hart J , Jones KB , Jordan JT , Kim RH , Lindsay D , Miller C , Nishida Y , Proszek P , Serrano J , Sundby RT , Szymanski JJ , Ullrich NJ , Viskochil D , Wang X ,   Genomics of MPNST (GeM) Consortium, Snuderl M , Park PJ , Flanagan AM , Hirbe AC , Pillay N , Miller DT
Published: May 2022

Malignant peripheral nerve sheath tumour (MPNST) is an aggressive soft-tissue sarcoma that arises in peripheral nerves. MPNST occurs either sporadically or in people with neurofibromatosis type 1 (NF1), a common cancer predisposition syndrome caused by germline pathogenic variants in NF1. Although MPNST is the most common cause of death and morbidity for individuals with NF1, the molecular underpinnings of MPNST pathogenesis remain unclear. Here, we report the analysis of whole-genome sequencing, multi-regional exome sequencing, transcriptomic and methylation profiling data for 95 MPNSTs and precursor lesions (64 NF1-related; 31 sporadic) from 77 individuals. Early events in tumour evolution include biallelic inactivation of NF1 followed by inactivation of CDKN2A and in some cases also TP53 and polycomb repressive complex 2 (PRC2) genes. Subsequently, both sporadic and NF1-related MPNSTs acquire a high burden of somatic copy number alterations (SCNAs). Our analysis revealed distinct pathways of tumour evolution and immune infiltration associated with inactivation of PRC2 genes and H3K27 trimethylation (H3K27me3) status. Tumours with loss of H3K27me3 evolve through extensive chromosomal losses with retention of chromosome 8 heterozygosity followed by whole genome doubling and chromosome 8 amplification. These tumours show lower levels of immune cell infiltration with low cytotoxic activity and low expression of immune checkpoints. In contrast, tumours with retention of H3K27me3 evolve through extensive genomic instability in the absence of recurrent alterations and exhibit an immune cell-rich phenotype. Specific SCNAs detected in both tumour samples and cell-free DNA (cfDNA) act as a surrogate for loss of H3K27me3 and immune infiltration, and predict prognosis. Our results suggest that SCNA profiling of tumour or cfDNA could serve as a biomarker for early diagnosis and to stratify patients into prognostic and treatment-related subgroups.
HIV integration in the human brain is linked to microglial activation and 3D genome remodeling
Authors: Plaza-Jennings Amara L. , Valada Aditi , O’Shea Callan , Iskhakova Marina , Hu Benxia , Javidfar Behnam , Hutta Gabriella Ben , Lambert Tova , Murray Jacinta , Kassim Bibi , Chandrasekaran Sandhya , Chen Benjamin K. , Morgello Susan , Won Hyejung , Akbarian Schahram
Published: May 2022

Exploration of genome organization and function in the HIV infected brain is critical to aid in the development of treatments for HIV-associated neurocognitive disorder (HAND) and HIV cure strategies. Here, we generated a resource comprised of single nuclei transcriptomics, complemented by cell-type-specific Hi-C chromosomal conformation (‘3D genome’) and viral integration site sequencing (IS-seq) in frontal brain tissues from individuals with HIV encephalitis (HIVE), HIV-infected people without encephalitis (HIV+), and HIV uninfected (HIV-) controls. We observed profound 3D genomic reorganization of open/repressive (A/B) compartment structures encompassing 6.4% of the HIVE microglial genome that was associated with transcriptomic reprogramming, including down-regulation of homeostasis and synapse-related functions and robust activation of interferon signaling and cell migratory pathways. HIV RNA was detected in 0.003% of all nuclei in HIVE brain, predominantly in the most activated microglia where it ranked as the second most highly expressed transcript. Microglia from HIV+ brains showed, to a lesser extent, similar transcriptional alterations. IS-seq recovered 1,221 insertion events in glial nuclei that were enriched for chromosomal domains newly mobilized into a permissive chromatin environment in HIVE microglia. Brain and peripheral myeloid cell integration revealed a preference overall for transcription-permissive chromatin, but robust differences in the frequency of recurrent insertions, intergenic integration, and enrichment for pre-integration complex-associated factors at integration sites. Our resource highlights critical differences in the genomic patterns of HIV infection in brain versus blood and points to a dynamic interrelationship between inflammation-associated 3D genome remodeling and successful integration in brain.
Enhanced cognitive interference during visuomotor tasks may cause eye-hand dyscoordination
Authors: Singh Tarkeshwar , Rizzo John R , Bonnet Cédrick , Semrau Jennifer , Herter Troy M
Published: May 2022

In complex visuomotor tasks, such as cooking, people make many saccades to continuously search for items before and during reaching movements. These tasks require use of short-term memory and task-switching (e.g., switching search between vegetables and spices). Cognitive load may affect visuomotor performance by increasing the demands on mental processes mediated by the prefrontal cortex, but mechanisms remain unclear. It is also unclear how patients with neurological injuries, e.g., stroke survivors, manage greater cognitive loads during visuomotor tasks. Using the Trail-Making Test, we have previously shown that stroke survivors make many more saccades, which are associated limb movements that are less smooth and slower. In this test, participants search for and make reaching movements towards twenty-five numbers and letters. It has a simple variant (Trails-A), and a cognitively challenging variant (Trails-B) that requires alphanumeric switching. The switching makes the task gradually harder as the Trails-B trial progresses (greater cognitive load). Here, we show that stroke survivors and healthy controls made many more saccades and had longer fixations as the Trails-B trial progressed. In addition, reaching speed slowed down for controls in Trails-B. We propose a mechanism where enhanced cognitive load may reduce inhibition from the prefrontal cortex and disinhibit the ocular motor system into making more saccades. These additional saccades may subsequently slow down motor function by disrupting the visual feedback loops used to control limb movements. These findings augment our understanding of the mechanisms that underpin cognitive interference dynamics when visual, ocular, and limb motor systems interact in visuocognitive motor tasks.

NEW & Noteworthy

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We used a neuropsychological test called the Trails-Making-test and analyze patterns of eye and reaching movements in controls and stroke survivors. We characterized how gaze and reaching movements change within a trial in the easier Trails-A and the more cognitively challenging Trails-B variant that requires alphanumeric switching. We found that as the Trails-B trial progressed participants made more saccadic eye movements and longer fixations, likely because of greater cognitive load.