bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexuality Transmitted Infections Risk and Interstate Sexual Networks among Men Who Have Sex with Men in New England
Authors: Ibanhes Fernando H. , Fenn Natalie , Le Brazidec Danielle , Napoleon Siena , Predmore Zachary , Skinner Alexandra , Zanowick-Marr Alex , Galipeau Drew , Raifman Julia , Dean Lorraine T. , Chan Philip A.
Published: April 2023

By investigating relationships between sexual mobility and STI risk factors among men who have sex with men, we found that past STI history, number of sexual partners, and substance use are associated with increased odds of interstate sexual encounters, suggesting that interjurisdictional approaches to STI prevention are needed.
Performance of a Provider-Assigned Functional Outcome Score in Critically Ill Children
Authors: Wilson Natalie E. , Su Felice , DaCar Allie , Chang Nathan , Kapphahn Kristopher , Schroeder Alan R. , Tawfik Daniel S. , Knight Lynda , Rasmussen Lindsey
Published: April 2023

Objectives:

Determine agreement between Pediatric Cerebral Performance Category (PCPC) scores integrated into clinical workflow and traditional investigator-assigned scores.

Design:

Longitudinal study.

Setting:

A single-center quaternary-care academic institution.

Subjects:

Children admitted to the PICU between November 2019 and April 2020.

Interventions:

Providers assigned PCPC scores as part of daily workflow. Investigators assigned scores using retrospective chart review.

Measurements and Main Results:

Of 803 patients admitted to the PICU, 782 survived and were included. Admission and discharge scores were recorded in 95% and 90% of patients, respectively. Agreement between provider- and investigator-assigned scores was excellent, with a weighted kappa of 0.87 (95% CI, 0.84–0.90) and 0.80 (95% CI, 0.76–0.84) for admission and discharge.

Conclusions:

Provider-assigned PCPC scores, documented as standard of care, are largely concordant with retrospective investigator-assigned scores. Measurement of cognitive functional status can be successfully integrated into daily provider workflow for use in the clinical, quality improvement, and research arenas.
Treatment of Esophageal Perforation: Endoscopic Vacuum-Assisted Closure
Authors: Barnett Grafton S. , Kimsey Kathryn M. , Shieh Hester F. , Smithers C. Jason , de Vries Jonathan M. , Mouch Jack , Wilsey Michael
Published: April 2023

Surgical repair of type C esophageal atresia (EA) with distal tracheoesophageal fistula (TEF) is complicated by an anastomotic leak in 10%–30% of cases with associated morbidity. A novel procedure in the pediatric population, endoscopic vacuum-assisted closure (EVAC), accelerates the healing of esophageal leaks by using the effects of VAC therapy, including fluid removal and stimulation of granulation tissue formation. We report 2 additional cases of chronic esophageal leak treated with EVAC in EA patients. The first is a patient with a previously repaired type C EA/TEF and left congenital diaphragmatic hernia complicated by an infected diaphragmatic hernia patch erosion into the esophagus and colon. Additionally, we discuss a second case using EVAC for early anastomotic leak following type C EA/TEF repair in a patient who was later found to have a distal congenital esophageal stricture.
A New Treatment Program: Focused Integrated Team-based Treatment Program for Bipolar Disorder (FITT-BD)
Authors: Sylvia Louisa G. , Tovey Roberta E. , Katz Douglas , Boccagno Chelsea , Stromberg Audrey R. , Peters Amy T. , Temes Christina M. , Gold Alexandra K. , Mow Jessica , Puvanich Nicha , Albury Evan A. , Stephan Nicole J. , Faria Caylin M. , Nierenberg Andrew A. , Kamali Masoud P.
Published: April 2023

Objective:

Bipolar disorder (BD) is complicated by a dynamic, chronic course along with multiple comorbid psychiatric and medical conditions, making it challenging for clinicians to treat and patients to thrive. To efficiently manage the complexity of BD and help patients recover, we developed a Focused Integrated Team-based Treatment Program for Bipolar Disorder (FITT-BD). The purpose of this paper is to describe how we developed this clinic and the lessons we learned.

Methods:

We developed FITT-BD by integrating strategies from stepped care, collaborative care, and learning health care systems. We describe the rationale, details, and lessons learned in developing FITT-BD.

Results:

By integrating stepped care, collaborative care, and a learning health care system approach, FITT-BD aims to reduce barriers to care, leverage the expertise of a multidisciplinary treatment team, ensure patient-centeredness, and use assessments to inform and continuously improve outcomes in real time. We learned that there are challenges in the creation of a web-based application that tracks the treatment of patients within a network of hospitals.

Conclusions:

The success of FITT-BD will be determined by the degree to which it can increase treatment access, improve treatment adherence, and help individuals with BD achieve their treatment goals. We expect that FITT-BD will improve outcomes in the context of ongoing clinical care.

Public Health Significance:

The treatment of BD is challenging and complex. We propose a new treatment model for BD: FITT-BD. We expect that this program will be a patient-centered approach that improves outcomes in the context of ongoing clinical care for patients with BD.
Recent Advances in the Treatment of Brachial Plexus Birth Injury
Authors: Zuo Kevin J. , Ho Emily S. , Hopyan Sevan , Clarke Howard M. , Davidge Kristen M.
Published: April 2023

Learning Objectives:

After studying this article, the participant should be able to: 1. Describe methods of clinical evaluation for neurologic recovery in brachial plexus birth injury. 2. Understand the role of different diagnostic imaging modalities to evaluate the upper limb. 3. List nonsurgical strategies and surgical procedures to manage shoulder abnormality. 4. Explain the advantages and disadvantages of microsurgical nerve reconstruction and distal nerve transfers in brachial plexus birth injury. 5. Recognize the prevalence of pain in this population and the need for greater sensory outcomes evaluation.

Brachial plexus birth injury (BPBI) results from closed traction injury to the brachial plexus in the neck during an infant’s vertex passage through the birth canal. Although spontaneous upper limb recovery occurs in most instances of BPBI, some infants do not demonstrate adequate motor recovery within an acceptable timeline and require surgical intervention to restore upper limb function. This article reviews major advances in the management of BPBI in the past decade that include improved understanding of shoulder pathology and its impact on observed motor recovery, novel surgical techniques, new insights in sensory function and pain, and global efforts to develop standardized outcomes assessment scales.
Effects of cannabis legalization on the use of cannabis and other substances
Authors: Assanangkornchai Sawitri , Kalayasiri Rasmon , Ratta-apha Woraphat , Tanaree Athip
Published: April 2023

Purpose of review

As more jurisdictions legalize cannabis for non-medical use, the evidence on how legalization policies affect cannabis use and the use of other substances remains inconclusive and contradictory. This review aims to summarize recent research findings on the impact of recreational cannabis legalization (RCL) on cannabis and other substance use among different population groups, such as youth and adults.

Recent findings

Recent literature reports mixed findings regarding changes in the prevalence of cannabis use after the adoption of RCL. Most studies found no significant association between RCL and changes in cannabis use among youth in European countries, Uruguay, the US, and Canada. However, some studies have reported increases in cannabis use among youth and adults in the US and Canada, although these increases seem to predate RCL. Additionally, there has been a marked increase in unintentional pediatric ingestion of cannabis edibles postlegalization, and an association between RCL and increased alcohol, vaping, and e-cigarette use among adolescents and young adults.

Overall, the effects of cannabis legalization on cannabis use appear to be mixed. Further monitoring and evaluation research is needed to provide longer-term evidence and a more comprehensive understanding of the effects of RCL.
Rapid opioid overdose response system technologies
Authors: Tay Wee Teck Joseph , Oteo Alberto , Baldacchino Alexander
Published: April 2023

Purpose of review

Opioid overdose events are a time sensitive medical emergency, which is often reversible with naloxone administration if detected in time. Many countries are facing rising opioid overdose deaths and have been implementing rapid opioid overdose response Systems (ROORS). We describe how technology is increasingly being used in ROORS design, implementation and delivery.

Recent findings

Technology can contribute in significant ways to ROORS design, implementation, and delivery. Artificial intelligence-based modelling and simulations alongside wastewater-based epidemiology can be used to inform policy decisions around naloxone access laws and effective naloxone distribution strategies. Data linkage and machine learning projects can support service delivery organizations to mobilize and distribute community resources in support of ROORS. Digital phenotyping is an advancement in data linkage and machine learning projects, potentially leading to precision overdose responses. At the coalface, opioid overdose detection devices through fixed location or wearable sensors, improved connectivity, smartphone applications and drone-based emergency naloxone delivery all have a role in improving outcomes from opioid overdose. Data driven technologies also have an important role in empowering community responses to opioid overdose.

This review highlights the importance of technology applied to every aspect of ROORS. Key areas of development include the need to protect marginalized groups from algorithmic bias, a better understanding of individual overdose trajectories and new reversal agents and improved drug delivery methods.
Historical DNA from a rediscovered nineteenth-century paratype reveals genetic continuity of a Bahamian hutia (
Geocapromys ingrahami
) population
Authors: LeFebvre Michelle J. , Mychajliw Alexis M. , Harris George B. , Oswald Jessica A.
Published: April 2023

Past and ongoing human activities have shaped the geographical ranges and diversity of species. New genomic techniques applied to degraded samples, such as those from natural history collections, can uncover the complex evolutionary consequences of human pressures and generate baselines for interpreting magnitudes of species loss or persistence relevant to conservation. Here we integrate mitogenomic data with historical records from a recently rediscovered Bahamian hutia (
Geocapromys ingrahami
; (FMP Z02816)) specimen at the Fairbanks Museum & Planetarium (Vermont, USA) to determine when and where the specimen was collected and to place it in a phylogenetic context with specimens that both predate (palaeontological) and postdate (archaeological) human arrival in The Bahamas. We determined that this specimen was part of the same population as the named holotype specimen in 1891 on East Plana Cay (EPC). Bahamian hutia populations were widely extirpated following European colonization. Today, EPC hosts the last remaining natural Bahamian hutia population. Mitogenomic data places the focal specimen within the southern Bahamian hutia population, which is now largely restricted to EPC. The results reveal previously undocumented genetic continuity among the EPC population for at least the past 500 years, highlighting how ‘dark’ museum specimens inform new conservation-relevant understandings of diversity.
Distinct healthy and atopic canine gut microbiota is influenced by diet and antibiotics
Authors: Sinkko Hanna , Lehtimäki Jenni , Lohi Hannes , Ruokolainen Lasse , Hielm-Björkman Anna
Published: April 2023

The rising trend in non-communicable chronic inflammatory diseases coincides with changes in Western lifestyle. While changes in the human microbiota may play a central role in the development of chronic diseases, estimating the contribution of associated lifestyle factors remains challenging. We studied the influence of lifestyle—diet, antibiotic use, and residential environment with housing and family—on the gut microbiota of healthy and owner-reported atopic pet dogs, searching for associations between the lifestyle factors, atopy and microbiota. The results showed that atopic and healthy dogs had contrasting gut microbial composition. The gut microbiota also differed between two breeds, Labrador Retriever and Finnish Lapphund, selected for our study. Among all lifestyle factors studied, diet was most significantly associated with gut microbiota but only weakly with atopic symptoms. Thus, diet- and atopy-associated changes in the microbiota were not interrelated. Instead, the severity of symptoms was positively associated with the usage of antibiotics, which in turn was associated with the microbiota composition. Urban lifestyle was significantly associated with the increased prevalence of allergies but not with the gut microbiota. Our results from pet dogs supported previous evidence from humans, demonstrating that antibiotics, gut microbiota and atopic manifestation are interrelated. This congruence suggests that canine atopy might be a promising model for understanding the aetiology of human allergy.
Effects of domestication and captive breeding on reaction to moving objects: implications for avoidance behaviours of masu salmon
Oncorhynchus masou
Authors: Hasegawa Koh , Nakae Masanori , Miyamoto Kouta
Published: April 2023

Domestication and captive breeding can compromise the obstacle- and predator-avoidance capabilities of animals in the wild. Whereas previous studies only examined these effects in combination, here we examine them individually by comparing the abilities of wild, F1 (offspring of wild parents) and captive-bred (approx. F15) masu salmon
Oncorhynchus masou
to avoid a falling object under experimental conditions. Rates of avoidance failure were low (wild, 12.5%; F1, 10.7%; captive-bred, 8%) under light conditions, but increased under dark conditions (wild, 11.1%; F1, 32.1%; captive-bred, 60.0%). We attribute the elevated avoidance failure rate among F1 fish to the lack of learning opportunities in hatchery environments (i.e. domestication), and the further elevation of avoidance failure rate among captive-bred fish to the degradation of sensory organ function (i.e. captive breeding). These results imply reduced survival rates for F1 and captive-bred fish in the wild and are consistent with the low stocking efficiencies reported for captive-bred masu salmon.
Generalized higher-order Freud weights
Authors: Clarkson Peter A. , Jordaan Kerstin , Loureiro Ana
Published: April 2023

We discuss polynomials orthogonal with respect to a semi-classical generalized higher-order Freud weight

ω
(
x
;
t
,
λ
)
=

|

x

|

2
λ
+
1

exp
⁡
(
t

x
2

−

x

2
m

)
,

x
∈

R

,

with parameters

λ
>
−
1

,

t
∈

R

and

m
=
2
,
3
,
…

. The sequence of generalized higher-order Freud weights for

m
=
2
,
3
,
…

, forms a hierarchy of weights, with associated hierarchies for the first moment and the recurrence coefficient. We prove that the first moment can be written as a finite partition sum of generalized hypergeometric

 
1

F
m

functions and show that the recurrence coefficients satisfy difference equations which are members of the first discrete Painlevé hierarchy. We analyse the asymptotic behaviour of the recurrence coefficients and the limiting distribution of the zeros as

n
→
∞

. We also investigate structure and other mixed recurrence relations satisfied by the polynomials and related properties.
Life-history responses to temperature and seasonality mediate ectotherm consumer–resource dynamics under climate warming
Authors: Twardochleb Laura A. , Zarnetske Phoebe L. , Klausmeier Christopher A.
Published: April 2023

Climate warming is altering life cycles of ectotherms by advancing phenology and decreasing generation times. Theoretical models provide powerful tools to investigate these effects of climate warming on consumer–resource population dynamics. Yet, existing theory primarily considers organisms with simplified life histories in constant temperature environments, making it difficult to predict how warming will affect organisms with complex life cycles in seasonal environments. We develop a size-structured consumer–resource model with seasonal temperature dependence, parameterized for a freshwater insect consuming zooplankton. We simulate how climate warming in a seasonal environment could alter a key life-history trait of the consumer, number of generations per year, mediating responses of consumer–resource population sizes and consumer persistence. We find that, with warming, consumer population sizes increase through multiple mechanisms. First, warming decreases generation times by increasing rates of resource ingestion and growth and/or lengthening the growing season. Second, these life-history changes shorten the juvenile stage, increasing the number of emerging adults and population-level reproduction. Unstructured models with similar assumptions found that warming destabilized consumer–resource dynamics. By contrast, our size-structured model predicts stability and consumer persistence. Our study suggests that, in seasonal environments experiencing climate warming, life-history changes that lead to shorter generation times could delay population extinctions.
Striving for humane deaths for laboratory mice: hypobaric hypoxia provides a potential alternative to carbon dioxide exposure
Authors: Clarkson J. M. , Martin J. E. , Sparrey J. , Leach M. C. , McKeegan D. E. F.
Published: April 2023

Killing is often an unavoidable and necessary procedure for laboratory mice involved in scientific research, and providing a humane death is vital for public acceptance. Exposure to carbon dioxide (CO
2
) gas is the most widely used methodology despite well proven welfare concerns. Consequently, the continued use of CO
2
and its globally permitted status in legislation and guidelines presents an ethical dilemma for users. We investigated whether killing with hypobaric hypoxia via gradual decompression was associated with better welfare outcomes for killing laboratory mice. We compared the spontaneous behaviour of mice exposed to CO
2
, decompression or sham conditions, and used analgesic or anxiolytic interventions to determine their relative welfare impact. Gradual decompression resulted in longer times to unconsciousness and death and the pharmacological interventions support the notion of a minimally negative animal experience, while providing further evidence for pain and anxiety associated with exposure to CO
2
. Decompression resulted in moderate ear haemorrhage, but our welfare assessment suggests this may happen when mice are unconscious. Hence, gradual decompression could be the basis of significant refinement for killing laboratory mice. Future work should corroborate behaviour with neurobiological markers of loss of consciousness to verify the conscious phase of concern for animal welfare.
Range restricted old and young lineages show the southern Western Ghats to be both a museum and a cradle of diversity for woody plants
Authors: Gopal Abhishek , Bharti D. K. , Page Navendu , Dexter Kyle G. , Krishnamani Ramanathan , Kumar Ajith , Joshi Jahnavi
Published: April 2023

The Western Ghats (WG) mountain chain is a global biodiversity hotspot with high diversity and endemicity of woody plants. The latitudinal breadth of the WG offers an opportunity to determine the evolutionary drivers of latitudinal diversity patterns. We examined the spatial patterns of evolutionary diversity using complementary phylogenetic diversity and endemism measures. To examine if different regions of the WG serve as a museum or cradle of evolutionary diversity, we examined the distribution of 470 species based on distribution modelling and occurrence locations across the entire region. In accordance with the expectation, we found that the southern WG is both a museum and cradle of woody plant evolutionary diversity, as a higher proportion of both old and young evolutionary lineages are restricted to the southern WG. The diversity gradient is likely driven by high geo-climatic stability in the south and phylogenetic niche conservatism for moist and aseasonal sites. This is corroborated by persistent lineage nestedness at almost all evolutionary depths (10–135 million years), and a strong correlation of evolutionary diversity with drought seasonality, precipitation and topographic heterogeneity. Our results highlight the global value of the WG, demonstrating, in particular, the importance of protecting the southern WG—an engine of plant diversification and persistence.
Increased male-induced harm in response to female-limited selection: interactive effects between intra- and interlocus sexual conflict?
Authors: Romero-Haro Ana Ángela , Pérez-Rodríguez Lorenzo , Tschirren Barbara
Published: April 2023

Interlocus sexual conflict (IRSC) occurs because of shared interactions that have opposite effects on male and female fitness. Typically, it is assumed that loci involved in IRSC have sex-limited expression and are thus not directly affected by selective pressures acting on the other sex. However, if loci involved in IRSC have pleiotropic effects in the other sex, intersexual selection can shape the evolutionary dynamics of conflict escalation and resolution, as well as the evolution of reproductive traits linked to IRSC loci, and vice versa. Here we used an artificial selection approach in Japanese quail (
Coturnix japonica
) to test if female-limited selection on reproductive investment affects the amount of harm caused by males during mating. We found that males originating from lines selected for high female reproductive investment caused more oxidative damage in the female reproductive tract than males originating from lines selected for low female reproductive investment. This male-induced damage was specific to the oviduct and not found in other female tissues, suggesting that it was ejaculate-mediated. Our results suggest that intersexual selection shapes the evolution of IRSC and that male-induced harm may contribute to the maintenance of variation in female reproductive investment.
Diagnostic performance of plasma Aβ1-42, Aβ1-40and pTau181in the LUMIPULSE automated platform for the detection of Alzheimer disease
Authors: Arranz Javier , Zhu Nuole , Rubio-Guerra Sara , Rodríguez-Baz íñigo , Carmona-Iragui María , Barroeta Isabel , Illán-Gala Ignacio , Santos-Santos Miguel , Fortea Juan , Lleó Alberto , Tondo Mireia , Alcolea Daniel
Published: April 2023

BACKGROUND

Recently-developed blood markers for Alzheimer’s (AD) detection have high accuracy but usually require ultra-sensitive analytic tools not commonly available in clinical laboratories.

METHODS

We analyzed plasma samples from 367 consecutive participants in the SPIN cohort, comprising 302 euploid participants (67 cognitively unimpaired, 136 participants with mild cognitive impairment, and 99 with dementia) and 65 with Down Syndrome (46 non-demented and 19 with AD dementia). Participants were classified according to CSF biomarkers status using the AT(N) system. Plasma Aβ1–42, Aβ1–40and pTau181were measured in the fully-automated LUMIPULSE platform. We used ANOVA to compare plasma biomarkers concentrations between AT(N) groups, evaluated Spearman’s correlation between plasma and CSF and performed ROC analyses to assess their diagnostic accuracy to detect AD.

RESULTS

Plasma pTau181concentration was higher in A+T+ than A+T- and A-T-, and in A+T- and A-T+ than A-T-. The plasma Aβ1–42/Aβ1–40ratio was lower in A+T+ and A+T- compared to A-T-. pTau181and the Aβ1–42/Aβ1–40ratio showed moderate correlation between plasma and CSF (Rho=0.66 and 0.65, respectively). The areas under the ROC curve (AUC) to discriminate A+T+ from A-T- participants were 0.91 for pTau181and 0.86 for Aβ1–42/Aβ1–40. The combination of both measures yielded an AUC=0.94. Chronic kidney disease (CKD) was related to increased plasma biomarker concentrations, but ratios were not significantly affected.

CONCLUSION

The feasibility and performance of plasma-based biomarker measurements on an automated platform showed high diagnostic accuracy and hold great promise for the diagnostic process of AD.

What is already known on this topic

Blood biomarkers have shown high accuracy to detect AD pathophysiology. The feasibility of those biomarkers in different platforms and the influence of comorbidities in their concentrations needs to be studied.

What this study adds

We analyze the feasibility and diagnostic performance of AD biomarkers measured in a fully-automated platform and assess how comorbidities affect their concentrations.

How this study might affect research, practice, or policy

The measurement of plasma AD biomarkers in an automated platform yields high accuracy to detect AD pathophysiology and would be easy to implement. Plasma AD biomarker concentrations are increased in chronic kidney disease, and in this context, the use of ratios would be more reliable.
Suboptimal Sleep Duration is Associated with Poorer Neuroimaging Brain Health Profiles
Authors: Clocchiatti-Tuozzo Santiago , Rivier Cyprien , Renedo Daniela , Torres Lopez Victor M , Geer Jacqueline , Miner Brienne , Yaggi Henry , de Havenon Adam , Payabvash Sam , Sheth Kevin N , Gill Thomas M , Falcone Guido J
Published: April 2023

Background

Cardiovascular health optimization during middle age benefits brain health. The American Heart Association’s Life’s Simple 7 recently added sleep duration as a key determinant of cardiovascular health becoming the Life’s Essential 8. We tested the hypothesis that suboptimal sleep duration is associated with poorer neuroimaging brain health profiles in asymptomatic middle-aged adults.

Methods

We conducted a prospective MRI neuroimaging study in middle-aged persons without stroke, dementia, or multiple sclerosis enrolled in the UK Biobank. Self-reported sleep duration was categorized as short (<7 hours), optimal (7-<9 hours), or long (≥9 hours). Evaluated neuroimaging markers of brain health included white matter hyperintensities (presence and volume) and diffusion tensor imaging metrics (fractional anisotropy and mean diffusivity) evaluated in 48 distinct neuroanatomical regions. We used multivariable logistic and linear regression models, as appropriate, to test for association between sleep duration and neuroimaging markers of brain health.

Results

We evaluated 39,502 middle-aged persons (mean age 55, 53% female). Of these, 28,712 (72.7%) had optimal, 8,422 (21.3%) short, and 2,368 (6%) long sleep. Compared to optimal sleep, short sleep was associated with higher risk (OR 1.11; 95% CI 1.05-1.17; P<0.001) and larger volume (beta=0.06, SE=0.01; P<0.001) of white matter hyperintensities, while long sleep was associated with higher volume (beta=0.04, SE=0.02; P=0.01) but not higher risk (P>0.05) of white matter hyperintensities. Short (beta=0.03, SE=0.01; P=0.004) and long sleep (beta=0.07, SE=0.02; P<0.001) were associated with worse fractional anisotropy, while only long sleep associated with worse mean diffusivity (beta=0.05, SE=0.02; P=0.005).

Conclusions

Among middle-aged adults without clinically observed neurological disease, suboptimal sleep duration is associated with poorer neuroimaging brain health profiles. Because the evaluated neuroimaging markers precede stroke and dementia by several years, our findings support early interventions aimed at correcting this modifiable risk factor.
A study of gene expression in the living human brain
Authors: Liharska Lora E. , Park You Jeong , Ziafat Kimia , Wilkins Lillian , Silk Hannah , Linares Lisa M. , Thompson Ryan C. , Vornholt Eric , Sullivan Brendan , Cohen Vanessa , Kota Prashant , Feng Claudia , Cheng Esther , Johnson Jessica S. , Rieder Marysia-Kolbe , Huang Jia , Scarpa Joseph , Polanco Jairo , Moya Emily , Hashemi Alice , Levin Matthew A. , Nadkarni Girish N. , Sebra Robert , Crary John , Schadt Eric E. , Beckmann Noam D. , Kopell Brian H. , Charney Alexander W.
Published: April 2023

A goal of medical research is to determine the molecular basis of human brain health and illness. One way to achieve this goal is through observational studies of gene expression in human brain tissue. Due to the unavailability of brain tissue from living people, most such studies are performed using tissue from postmortem brain donors. An assumption underlying this practice is that gene expression in the postmortem human brain is an accurate representation of gene expression in the living human brain. Here, this assumption – which, until now, had not been adequately tested – is tested by comparing human prefrontal cortex gene expression between 275 living samples and 243 postmortem samples. Expression levels differed significantly for nearly 80% of genes, and a systematic examination of alternative explanations for this observation determined that these differences are not a consequence of cell type composition, RNA quality, postmortem interval, age, medication, morbidity, symptom severity, tissue pathology, sample handling, batch effects, or computational methods utilized. Analyses integrating the data generated for this study with data from earlier landmark studies that used tissue from postmortem brain donors showed that postmortem brain gene expression signatures of neurological and mental illnesses, as well as of normal traits such as aging, may not be accurate representations of these gene expression signatures in the living brain. By using tissue from large cohorts living people, future observational studies of human brain biology have the potential to (1) determine the medical research questions that can be addressed using postmortem tissue as a proxy for living tissue and (2) expand the scope of medical research to include questions about the molecular basis of human brain health and illness that can only be addressed in living people (e.g., “What happens at the molecular level in the brain as a person experiences an emotion?”).
A generalizable functional connectivity signature characterizes brain dysfunction and links to rTMS treatment response in cocaine use disorder
Authors: Zhao Kanhao , Fonzo Gregory A. , Xie Hua , Oathes Desmond J. , Keller Corey J. , Carlisle Nancy , Etkin Amit , Garza-Villarreal Eduardo A , Zhang Yu
Published: April 2023

Cocaine use disorder (CUD) is a prevalent substance abuse disorder, and repetitive transcranial magnetic stimulation (rTMS) has shown potential in reducing cocaine cravings. However, a robust and replicable biomarker for CUD phenotyping is lacking, and the association between CUD brain phenotypes and treatment response remains unclear. Our study successfully established a cross-validated functional connectivity signature for accurate CUD phenotyping, using resting-state functional magnetic resonance imaging from a discovery cohort, and demonstrated its generalizability in an independent replication cohort. We identified phenotyping FCs involving increased connectivity between the visual network and dorsal attention network, and between the frontoparietal control network and ventral attention network, as well as decreased connectivity between the default mode network and limbic network in CUD patients compared to healthy controls. These abnormal connections correlated significantly with other drug use history and cognitive dysfunctions, e.g., non-planning impulsivity. We further confirmed the prognostic potential of the identified discriminative FCs for rTMS treatment response in CUD patients and found that the treatment-predictive FCs mainly involved the frontoparietal control and default mode networks. Our findings provide new insights into the neurobiological mechanisms of CUD and the association between CUD phenotypes and rTMS treatment response, offering promising targets for future therapeutic development.
A novel multimodal approach to improve upper extremity function after moderate-to-severe stroke
Authors: Sethi Amit , Pascual-leone Alvaro , Santarnecchi Emiliano , Almalki Ghaleb , Krishnan Chandramouli
Published: April 2023

Background

Interventions to recover upper extremity (UE) function after moderate-to-severe stroke are limited. Transcranial random noise stimulation (tRNS) is an emerging non-invasive technique to improve neuronal plasticity and may potentially augment functional outcomes when combined with existing interventions, such as functional electrical stimulation (FES).

Objective

The objective of this study was to investigate the feasibility and preliminary efficacy of combined tRNS and FES-facilitated task practice to improve UE impairment and function after moderate-to-severe stroke.

Methods

Fourteen individuals with UE weakness were randomized into one of two groups: 1) tRNS with FES-facilitated task practice, or 2) sham-tRNS with FES-facilitated task practice. Both groups involved 18 intervention sessions (3 per week for 6 weeks). We evaluated number of sessions completed, adverse effects, participant satisfaction, and intervention fidelity between two therapists. UE impairment (Fugl-Meyer Upper Extremity, FMUE), function (Wolf Motor Function Test, WMFT), participation (Stroke Impact Scale hand score, SIS-H), and grip strength were assessed at baseline, within 1 week and 3 months after completing the intervention.

Results

All participants completed the 18 intervention sessions. Participants reported minimal adverse effects (mild tingling in head). The two trained therapists demonstrated 93% adherence and 96% competency with the intervention protocol. FMUE and SIS-H improved significantly more in the tRNS group than in the sham-tRNS group at both timepoints (p≤0.05), and the differences observed exceeded the clinically meaningful differences for these scores. The WMFT and paretic hand grip strength improved in both groups after the intervention (p≤0.05), with no significant between group differences.

Conclusion

Our findings show for the first time that combining tRNS and FES-facilitated task practice is a feasible and promising approach to improve UE impairment and function after moderate-to-severe stroke.
Anxiety due to Long COVID is partially driven by activation of the tryptophan catabolite (TRYCAT) pathway
Authors: Al-Hakeim Hussein Kadhem , Abed Anwar Khairi , Almulla Abbas F. , Moustafa Shatha Rouf , Maes Michael
Published: April 2023

This study examines whether activation of the tryptophan catabolite (TRYCAT) pathway is associated with anxiety symptoms due to Long COVID. We selected 90 participants, 60 Long COVID patients and 30 individuals without any symptoms following acute CIVID-19 infection. Using cluster analysis and the Hamilton Anxiety Rating scale (HAMA) score, the pure HAMA anxiety score, serum tryptophan (TRP) and kynurenine (KYN), the KYN/TRP ratio (all measured during Long COVID), and oxygen saturation (SpO2) (measured during the acute phase of COVID-19), we were able to classify Long COVID patients into two distinct clusters with an adequate silhouette cohesion and separation index (0.58): cluster 1 (n=61) and cluster 2 (n=29). Cluster 2 patients had lower SpO2 and TRP levels, as well as higher KYN, KYN/TRP ratio, and HAMA scores than cluster 1. Regression analysis revealed that the KYN/TRP ratio explained 14.4% of the variance in the HAMA score (F=14.81, df=1/88, p=0.001). In addition, regression analysis revealed that SpO2 partially explained the variance in serum TRP (r=0.396, p=0.005), KYN/TRP ratio (r=-0.248, p=0.018), and the HAMA score (r=-0.279, p=0.008). The current data imply that decreased SpO2 during the acute phase of COVID-19 infection is predictive of anxiety caused by Long COVID. Our data reveal that around 32% of Long COVID patients have elevated IDO activity in association with elevated anxiety.
Transformer based deep learning denoising of single and multi-delay 3D Arterial Spin Labeling
Authors: Shou Qinyang , Zhao Chenyang , Shao Xingfeng , Jann Kay , Helmer Karl G. , Lu Hanzhang , Wang Danny JJ
Published: April 2023

Purpose

To present a Swin Transformer-based deep learning (DL) model for denoising of single-delay and multi-delay 3D arterial spin labeling (ASL) and compare its performance with convolutional neural network (CNN) methods.

Methods

Swin Transformer and CNN-based spatial denoising models were developed for single-delay ASL. The models were trained on 59 subjects (104 scans) and tested on 44 subjects (57 scans) from 3 different vendors. Spatiotemporal denoising models were developed using another dataset (6 subjects, 10 scans) of multi-delay ASL. A range of input conditions was tested for denoising single and multi-delay ASL respectively. The performance was evaluated using similarity metrics, spatial signal-to-noise ratio (SNR) and quantification accuracy of cerebral blood flow (CBF) and arterial transit time (ATT).

Results

Swin Transformer outperformed CNN-based networks, whereas pseudo-3D models showed better performance than 2D models for denoising single-delay ASL. The similarity metrics and image quality (SNR) improved with more slices in pseudo-3D models, and further improved when using M0 as input but introduced greater biases for CBF quantification. Pseudo-3D models with 3 slices as input achieved optimal balance between SNR and accuracy, which can be generalized to different vendors. For multi-delay, spatiotemporal denoising models had better performance than spatial-only models with reduced biases in fitted CBF and ATT maps.

Conclusions

Swin Transformer DL models provided better performance than CNN methods for denoising both single and multi-delay 3D ASL data. The proposed model offers flexibility to improve image quality and/or reduce scan time for 3D ASL to facilitate its clinical use.
A Mixed Methods System for the Assessment of Post Exertional Malaise in Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Stussman Barbara , Calco Brice , Norato Gina , Gavin Angelique , Chigurupati Snigdha , Nath Avindra , Walitt Brian
Published: April 2023

Background

A central feature of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is post exertional malaise (PEM), which is an acute worsening of symptoms after a physical, emotional and/or mental exertion. PEM is also a feature of Long COVID. Dynamic measures of PEM have historically included scaled questionnaires which have not been validated in ME/CFS. To enhance our understanding of PEM and how best to measure it, we conducted semi-structured qualitative interviews (QIs) at the same intervals as Visual Analog Scale (VAS) measures after a Cardiopulmonary Exercise Test (CPET).

Methods

Ten ME/CFS and nine healthy volunteers participated in a CPET. For each participant, PEM symptom VAS (7 symptoms) and semi-structured QIs were administered at six timepoints over 72 hours before and after a single CPET. QI data were used to plot the severity of PEM at each time point and identify the self-described most bothersome symptom for each patient. QI data were used to determine the symptom trajectory and peak of PEM. Performance of QI and VAS data were compared to each other using Spearman correlations.

Results

QIs documented that each ME/CFS volunteer had a unique PEM experience, with differences noted in the onset, severity, trajectory over time, and most bothersome symptom. No healthy volunteers experienced PEM. Scaled QI data were able to identify PEM peaks and trajectories, even when VAS scales were unable to do so due to known ceiling and floor effects. QI and VAS fatigue data corresponded well prior to exercise (baseline, r=0.7) but poorly at peak PEM (r=0.28) and with the change from baseline to peak (r=0.20). When the most bothersome symptom identified from QIs was used, these correlations improved (r=.0.77, 0.42. and 0.54 respectively) and reduced the observed VAS scale ceiling and floor effects.

Conclusion

QIs were able to capture changes in PEM severity and symptom quality over time in all the ME/CFS volunteers, even when VAS scales failed to do so. Information collected from QIs also improved the performance of VAS. Measurement of PEM can be improved by using a quantitative-qualitative mixed model approach.

Disclaimer

This research/work/investigator was supported (in part) by the Division of Intramural Research of the National Institutes of Health, NINDS. The content is solely the responsibility of the author(s) and does not necessarily represent the official views of the National Institutes of Health.
WITHDRAWN: Evaluation of Fourier Transform Infrared spectroscopy (IR Biotyper) as a complement to Whole genome sequencing (WGS) to characteriseEnterobacter cloacae,Citrobacter freundiiandKlebsiella pneumoniaeisolates recovered from hospital sinks
Authors: Aranega-Bou P , Cornbill C , Rodger G , Bird M , Moore G , Roohi A , Hopkins KL , Hopkins S , Ribeca P , Stoesser N , Lipworth SI
Published: April 2023

Withdrawal statement

The authors have withdrawn their manuscript due to becoming aware of methodology issues related to the curation of the training set used to determine cut-off values for Biotyper cluster assignation and lack of replicate measurements on different days for the isolates analysed. It is therefore unclear whether the conclusions of the manuscript are founded and no further work is possible to correct these issues as the instrument is no longer available to the authors. If you have any questions, please contact the corresponding author.
Estimation of Near-kink Reproduction Numbers During the Emergent Variants of the COVID-19 Pandemic: Log-quadratic and Forward-imputation Approach
Authors: Nakamoto Ichiro
Published: April 2023

Background

Sketching the major portraits of the COVID-19 epidemic when variants of the pathogen emerge is critical to inform the dynamics of disease transmission, reproduction (i.e., the average counts of individuals of secondary infections generated by an index individual infected by the virus) strength of the pathogen, and countermeasure strategies. Multiple approaches, including log-linear, EpiEstim (an R package generally utilized to estimate the evolution traits of epidemics), and near-log-linear techniques, have been exploited to evaluate the principal parameters such as basic and effective reproduction numbers of an epidemic outbreak.

Objective

This study focuses on the kink corner (i.e., sharp alternation of direction of the transmission curve) presenting differentiated log-quadratic traits where more infectious variants of viruses emerge at the diminishing transmission phase of an infectious disease.

Methods

A novel log-quadratic trending framework was proposed to project potentially unidentified cases (i.e., forward imputing approximately one week ahead) of COVID-19 around the kink, where the transmission of the pandemic initially lowered and accelerated subsequently, and exercised with the updated framework of classic EpiEstim and Log-linear model. I first compared the performance near the kink using the proposed technique versus the two traditional models taking into account a variety of levels of transmissibility, data distribution (Weibull, Gamma, and Lognormal distributions), and reporting rates (0.2, 0.4, 0.6, 0.8 and 1.0 respectively). Thereafter I utilized the revised framework on the outbreak data of four settings including Bulgaria, Japan, Poland, and South Korea from June to August 2022.

Results

The proposed framework reduced the estimation bias versus traditional EpiEstim and log-linear methods near the kink. The coverage estimates of 95% confidence intervals improved. The proposed forward-imputation method implied generally a consistent ascending trend of effective reproduction number estimation applying to a precipitous transition from diminishing to diverging scenarios versus the irregular zigzagging outcomes in classic methods when more contagious variants of the virus were present in the absence of effective vaccines.

Conclusions

The log-quadratic correction accounting for transmissibility, data distribution, reporting rates, sliding windows, and generation intervals improved the basic and effective reproduction numbers estimation at the kink corner versus the classic EpiEstim and log-linear models by refined amendment of curve fitting. This is of concern when essentially the fundamental transmission traits of a pandemic alter expeditiously and countermeasures are needed at the earlier variant phases of the transiting climax with the advancement of the pandemic.
Is Covid-19 Mortality “Like the Flu”? A Cumulative Death Rates Comparison
Authors: Wrigley-Field Elizabeth , Himmelstern Jessie
Published: April 2023

It has been common both to make and to resist comparisons that equate the Covid-19 pandemic to influenza. We take the comparison between Covid-19 and flu seriously by asking how many years of influenza and pneumonia deaths are needed for cumulative deaths to those two causes to equal the cumulative toll of the Covid-19 pandemic between March 2020 and February 2023—that is, three years of pandemic deaths. We find that in one state alone—Hawaii—three years of Covid-19 mortality is equivalent to influenza and pneumonia mortality in the three years preceding the Covid-19 pandemic. For all other states, at least nine years of flu and pneumonia are needed to match Covid-19; for the United States as a whole, seventeen years are needed; and for four states, more than 21 years (the maximum observable) are needed. These results provide an easy-to-understand calibration of flu as a heuristic for Covid-19, and vice versa.
Bifrontal transcranial direct current stimulation normalises learning rate adjustment in low mood
Authors: Sarrazin Verena , Overman Margot , Mezossy-Dona Luca , Browning Michael , O’Shea Jacinta
Published: April 2023

Background

Transcranial direct current stimulation (tDCS) applied to dorsolateral prefrontal cortex has mild to moderate antidepressant effects. Little is known about the mechanisms of action. Other antidepressant treatments have been shown to act in part by reducing negative biases, which are thought to play a causal role in the maintenance of depression. Negative biases are hypothesized to stem from aberrant reinforcement learning processes, more precisely from overestimation of the informativeness of negative outcomes. The aim of this study was to test whether bifrontal tDCS might normalise such aberrant reinforcement learning processes in depressed mood.

Methods

85 community volunteers with low mood received tDCS during (or before) the performance of a reinforcement learning task that manipulated the informativeness (volatility) of positive and negative outcomes. In two sessions participants received real or sham tDCS in counter-balanced order. Baseline performance (sham tDCS) was compared to a sample of healthy individuals (n = 40) to identify the effect of low mood on task performance. The impact of tDCS on task performance was assessed by contrasting real and sham tDCS.

Results

Low mood was characterised by decreased adjustment of loss relative to win learning rates in response to changes in informativeness. Bifrontal tDCS applied during task performance normalised this deficit by increasing the adjustment of loss learning rates to informativeness. Bifrontal tDCS applied before task performance had no effect indicating that the stimulation effect is cognitive state dependent.

Conclusions

Our study provides preliminary evidence that bifrontal tDCS can normalise aberrant reinforcement learning processes in low mood. Crucially, this was only the case if stimulation was applied during task performance, suggesting that combining tDCS with a concurrent cognitive manipulation might increase the functional impact on cognitive functions and potentially on emotional symptoms. Future studies are needed to test if the effect on learning processes might have a beneficial effect on mood itself.