bluuebunny/crossref_metadata_2025 huggingface dataset:
Ovarian clear cell cancer associated with Trousseau syndrome: A case report and literature review
Authors: You Yilin , Chen Xing , Jiang Yi , Cheng Wenjun
Published: November 2022

Rationale:

Trousseau syndrome is known as patients with tumors have a combination of multiple thrombi with systemic organ infarction. The incidence of ovarian clear cell cancer associated with Trousseau syndrome is relatively low. We report the case of a 41-year-old woman diagnosed with ovarian clear cell cancer with deep vein thrombosis and cerebral infarction who had a poor prognosis.

Patient concerns:

A 41-year-old woman was brought to our hospital with abdominal pain. Abdominal computerized tomography scan suggested large mass of ovarian origin which was considered an ovarian tumor with pelvic metastasis and peritoneal metastasis. Laboratory analyses indicated an elevated levels of serum tumor marker carbohydrate antigen 125 was 321.9 U/mL and the level of D-dimer was 16.71 mg/L.

Diagnosis:

The patient underwent pelvic mass aspiration was diagnosed with ovarian clear cell cancer. B-ultrasound revealed thrombosis of the lower limbs.

Interventions:

She underwent 2 neoadjuvant chemotherapies, along with anticoagulation therapy. However, it had a poor therapeutic effect, and the patient suffered from acute cerebral infarction that worsened.

Outcomes:

Chemotherapy and anticoagulation failed to stop the tumor and blood clot progression. The patient died 2 months after cerebral infarction without surgical treatment.

Lessons:

Gynecologists should be aware of the need for clinical suspicion of the risk of thrombosis during the treatment period of ovarian cancer and make careful decisions
Analysis of image quality by regulating beta function of BSREM reconstruction algorithm and comparison with conventional reconstructions in carcinoma breast studies of PET CT with BGO detector
Authors: Dwivedi Pooja , Sawant Viraj , Vajarkar Vishal , Vatsa Rakhee , Choudhury Sayak , Jha Ashish Kumar , Rangarajan Venkatesh
Published: November 2022

Background

The study aimed to evaluate the beta penalization factor of the BSREM reconstruction algorithm on a five-ring BGO-based PET CT system and compared it with conventional reconstructions.

Methods

Retrospective study involves 30 breast cancer patient data of 18F-fluorodeoxyglucose (18F-FDG) PET CT for reconstruction with OSEM, OSEM + PSF, and BSREM under variable β factors ranging from 200 to 600 in the steps of 50. Liver noise, lesion SUVmax, SBR, and SNR for each reconstruction were calculated. Quantitative parameters of each beta factor of BSREM were compared with OSEM and OSEM + PSF, using the Wilcoxon sign rank test with Bonferroni correction, a value of P < 0.002 was considered statistically significant. Visual scoring by two readers was also evaluated.

Results

Thirty lesions of mean size 1.91 ± 0.58 cm range (0.7–3.6 cm) were identified. Liver noise and SBR were reduced, whereas SNR was increased with an increasing β value of BSREM. In comparison with OSEM, liver noise was not significantly different from β200 and β250. SNR of OSEM was significantly lower than any other β factors and SBR of β factor less than 500 was significantly higher than OSEM. In comparison with OSEM + PSF, liver noise was not significantly different from β400 and β350–500 do not show a significant difference in SNR and SBR compared with OSEM + PSF. β350 scored highest under visual scoring with a moderate agreement.

Conclusion

The study quantitatively indicates the optimum beta range of β250–450 and the qualitative evaluation indicates that β350 is an optimum beta factor of BSREM in breast cancer cases for 18F-FDG WB-PET CT.
Building design for couple relationship maintenance in congregate dementia care
Authors: Ren Tori Hui , Strickfaden Megan
Published: November 2022

Objectives:

The main objectives of this article are to consider the relationships among couples, individuals, facility caregivers, and architectural design through 2 case studies that may influence maintaining couple relationships and the respective individuals’ quality of life.

Methods:

A phenomenological approach is taken through the case studies where the lived experiences of 2 couples—where each couple has one individual with and another without dementia—live in 2 different buildings. Multiple data collection methods included in-depth analysis of the building and grounds, interviews with residents and family members as well as facility caregivers and participant observations.

Results:

Both building designs featured suites with multiple rooms, independent living suites, and dementia care units to maintain couple-based routines as well as individuals’ needs. Having one suite located far away from the unit’s entrance hindered the spouse without dementia from maintaining connections outside the unit.

Conclusions:

The article highlights how building design can support as well as hinder the couple’s relationship maintenance and the individuals’ quality of life. We recommend considering building design opportunities for residents to maintain couple-based daily routines and for spousal residents to connect with the world outside the dementia care unit.
A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Trial of Radiopaque Islatravir-Eluting Subdermal Implants for Pre-exposure Prophylaxis Against HIV-1 Infection
Authors: Matthews Randolph P. , Zang Xiaowei , Barrett Stephanie E. , Koynov Athanas , Goodey Adrian , Heimbach Tycho , Weissler Vanessa L. , Leyssens Carlien , Reynders Tom , Xu Zhiqing , Rottey Sylvie , Vargo Ryan , Robertson Michael N. , Stoch S. Aubrey , Iwamoto Marian
Published: November 2022

Background:

Islatravir (MK-8591) is a deoxyadenosine analog in development for the treatment and prevention of HIV-1 infection. An islatravir-eluting implant could provide an additional option for pre-exposure prophylaxis (PrEP).

Setting:

Previous data support a threshold islatravir triphosphate concentration for PrEP of 0.05 pmol/106 cells in peripheral blood mononuclear cells. Prototype islatravir-eluting implants were previously studied to establish general tolerability and pharmacokinetics (PKs) of islatravir relative to the threshold level.

Methods:

In this randomized, double-blind, placebo-controlled, phase 1 trial, a next-generation radiopaque islatravir-eluting implant (48 mg, 52 mg, or 56 mg) or placebo implant was placed for a duration of 12 weeks in participants at low risk of HIV infection. Safety and tolerability, as well as PK for islatravir parent and islatravir triphosphate from plasma and peripheral blood mononuclear cells, were assessed throughout placement and 8 weeks after removal.

Results:

In total, 36 participants (8 active and 4 placebo per dose arm) were enrolled and completed this study. Implants were generally well tolerated, with no discontinuations due to an adverse event, and no clear dose-dependence in implant-related adverse events. No clinically meaningful relationships were observed for changes in laboratory values, vital signs, or electrocardiogram assessments. Mean islatravir triphosphate levels at day 85 (0.101–0.561 pmol/106 cells) were above the PK threshold for all dose levels.

Conclusion:

Islatravir administered using a subdermal implant has the potential to be an effective and well-tolerated method for administering PrEP to individuals at risk of acquiring HIV-1.
Impacts of assisted reproductive technology on perinatal outcomes and offspring health
Authors: Hong Jin , Sun Yi-Juan , Shu Yi-Min
Published: November 2022

Assisted reproductive technology (ART) has evolved rapidly over the last 40 years, offering hope to individuals and couples struggling with infertility. As technology continues to evolve, simulating a realistic female reproductive system environment has become a common goal for all types of ARTs, thereby reducing the impact of the artificial microenvironment on perinatal and offspring health. In this review, we provide a brief history of the development of each major ART and discuss the impact of ART on perinatal and offspring health. We also explore how the negative consequences of ART may be overcome and how its benefits can be maximized.
Advances in the pathophysiology of bipolar disorder
Authors: Wartchow Krista M. , Cordeiro Rafaela C. , Scaini Giselli
Published: November 2022

Purpose of review

Due to bipolar disorder clinical heterogeneity, a plethora of studies have provided new genetic, epigenetic, molecular, and cellular findings associated with its pathophysiology.

Recent findings

Genome-wide association studies and epigenetic evidence points to genotype–phenotype interactions associated with inflammation, oxidative stress, abnormalities in signaling pathways, hypothalamic–pituitary–adrenal axis, and circadian rhythm linked to mitochondrial dysfunction in bipolar disorder. Although the literature is constantly increasing, most of the genetic variants proposed as biomarkers remain to be validated by independent groups and use bigger samples and longitudinal approaches to enhance their power and predictive ability.

Regardless of which of the mechanisms described here plays a primary or secondary role in the pathophysiology of bipolar disorder, all of these interact to worsen clinical outcomes for patients. Identifying new biomarkers for early detection, prognosis, and response to treatment might provide novel targets to prevent progression and promote general well being.
Recent advances in sleep and depression
Authors: Mirchandaney Riya , Asarnow Lauren D. , Kaplan Katherine A.
Published: November 2022

Purpose of review

There is increasing interest in the connection between sleep disturbances and mood disorders. The purpose of this review is to summarize and evaluate current research on the role of sleep disturbance in the development of depression, as well as to describe recent advances in treatments that improve both sleep and depression symptoms.

Recent findings

Relevant publications included in this review cover a wide range of topics related to sleep and depression. Data from large longitudinal studies suggest that insomnia and evening circadian preference are unique risk factors for depression. Depression treatment studies indicate poorer outcomes for those with comorbid sleep disturbances. A few recent trials of cognitive behavioral therapy for insomnia and triple chronotherapy in unipolar depression have shown promising results.

Sleep disturbance is a modifiable risk factor in the development and maintenance of depression. In the context of current depression, although the data is mixed, some evidence suggests treating sleep disturbance can improve overall outcomes. Recent evidence also suggests that treating sleep disturbance may prevent the future depressive episodes.
Temperature regime during embryogenesis alters subsequent behavioural phenotypes of juvenile brown trout
Authors: Takatsu Kunio , Selz Oliver M. , Brodersen Jakob
Published: November 2022

Climate warming imposes a serious threat, especially to freshwater ecosystems in temperate and (sub)polar regions, which are often dominated by cold-adapted ectotherms. Although relatively intense warming during winter is common across the climatic regions, comparably little focus has been put on the organismal impacts of winter warming. Embryonic development, which is exceptionally susceptible to ambient temperature, occurs during winter in various freshwater ectotherms. Yet, our knowledge of the effects of increased temperature during embryogenesis on later life stages is limited. Using brown trout (
Salmo trutta
), we examined how a 1.5°C temperature increase from fertilization to hatching affects various traits at the onset of the free-swimming stage (i.e. a comparison between 3.5 and 5.0°C treatments). Although all hatchlings were kept at the same temperature (7.0°C) from hatching to the onset of the free-swimming stage for about two months, the temperature increase during embryogenesis substantially reduced key ecological behaviours, i.e. activity and exploration levels, at the onset of the free-swimming stage despite only marginal temperature effects on morphological and physiological traits at this stage. Given the importance of behavioural traits in early growth and survival, our study suggests a likely pathway through which subtle changes in mean winter temperature affect early fitness.
Biology and medicine in the landscape of quantum advantages
Authors: Cordier Benjamin A. , Sawaya Nicolas P. D. , Guerreschi Gian Giacomo , McWeeney Shannon K.
Published: November 2022

Quantum computing holds substantial potential for applications in biology and medicine, spanning from the simulation of biomolecules to machine learning methods for subtyping cancers on the basis of clinical features. This potential is encapsulated by the concept of a quantum advantage, which is contingent on a reduction in the consumption of a computational resource, such as time, space or data. Here, we distill the concept of a quantum advantage into a simple framework to aid researchers in biology and medicine pursuing the development of quantum applications. We then apply this framework to a wide variety of computational problems relevant to these domains in an effort to (i) assess the potential of practical advantages in specific application areas and (ii) identify gaps that may be addressed with novel quantum approaches. In doing so, we provide an extensive survey of the intersection of biology and medicine with the current landscape of quantum algorithms and their potential advantages. While we endeavour to identify specific computational problems that may admit practical advantages throughout this work, the rapid pace of change in the fields of quantum computing, classical algorithms and biological research implies that this intersection will remain highly dynamic for the foreseeable future.
Observations and models of across-wind flight speed of the wandering albatross
Authors: Richardson Philip L. , Wakefield Ewan D.
Published: November 2022

Wandering albatrosses exploit wind shear by dynamic soaring (DS), enabling rapid, efficient, long-range flight. We compared the ability of a theoretical nonlinear DS model and a linear empirical model to explain the observed variation of mean across-wind airspeeds of GPS-tracked wandering albatrosses. Assuming a flight trajectory of linked, 137° turns, a DS cycle of 10 s and a cruise airspeed of 16 m s
−1
, the theoretical model predicted that the minimum wind speed necessary to support DS is greater than 3 m s
−1
. Despite this, tracked albatrosses were observed in flight at wind speeds as low as 2 m s
−1
. We hypothesize at these very low wind speeds, wandering albatrosses fly by obtaining additional energy from updrafts over water waves. In fast winds (greater than 8 m s
−1
), assuming the same 10 s cycle period and a turn angle (TA) of 90°, the DS model predicts mean across-wind airspeeds of up to around 50 m s
−1
. In contrast, the maximum observed across-wind mean airspeed of our tracked albatrosses reached an asymptote at approximately 20 m s
−1
. We hypothesize that this is due to birds actively limiting airspeed by making fine-scale adjustments to TAs and soaring heights in order to limit aerodynamic force on their wings.
Estimating Zika virus attack rates and risk of Zika virus-associated neurological complications in Colombian capital cities with a Bayesian model
Authors: Charniga Kelly , Cucunubá Zulma M. , Walteros Diana M. , Mercado Marcela , Prieto Franklyn , Ospina Martha , Nouvellet Pierre , Donnelly Christl A.
Published: November 2022

Zika virus (ZIKV) is a mosquito-borne pathogen that caused a major epidemic in the Americas in 2015–2017. Although the majority of ZIKV infections are asymptomatic, the virus has been associated with congenital birth defects and neurological complications (NC) in adults. We combined multiple data sources to improve estimates of ZIKV infection attack rates (IARs), reporting rates of Zika virus disease (ZVD) and the risk of ZIKV-associated NC for 28 capital cities in Colombia. ZVD surveillance data were combined with post-epidemic seroprevalence data and a dataset on ZIKV-associated NC in a Bayesian hierarchical model. We found substantial heterogeneity in ZIKV IARs across cities. The overall estimated ZIKV IAR across the 28 cities was 0.38 (95% CrI: 0.17–0.92). The estimated ZVD reporting rate was 0.013 (95% CrI: 0.004–0.024), and 0.51 (95% CrI: 0.17–0.92) cases of ZIKV-associated NC were estimated to be reported per 10 000 ZIKV infections. When we assumed the same ZIKV IAR across sex or age group, we found important spatial heterogeneities in ZVD reporting rates and the risk of being reported as a ZVD case with NC. Our results highlight how additional data sources can be used to overcome biases in surveillance data and estimate key epidemiological parameters.
Simulations of surface charge density changes during the untreated solid tumour growth
Authors: Bory Prevez Henry , Soutelo Jimenez Argenis Adrian , Roca Oria Eduardo José , Heredia Kindelán José Alejandro , Morales González Maraelys , Villar Goris Narciso Antonio , Hernández Mesa Nibaldo , Sierra González Victoriano Gustavo , Infantes Frometa Yenia , Montijano Juan Ignacio , Cabrales Luis Enrique Bergues
Published: November 2022

Understanding untreated tumour growth kinetics and its intrinsic behaviour is interesting and intriguing. The aim of this study is to propose an approximate analytical expression that allows us to simulate changes in surface charge density at the cancer-surrounding healthy tissue interface during the untreated solid tumour growth. For this, the Gompertz and Poisson equations are used. Simulations reveal that the unperturbed solid tumour growth is closely related to changes in the surface charge density over time between the tumour and the surrounding healthy tissue. Furthermore, the unperturbed solid tumour growth is governed by temporal changes in this surface charge density. It is concluded that results corroborate the correspondence between the electrical and physiological parameters in the untreated cancer, which may have an essential role in its growth, progression, metastasis and protection against immune system attack and anti-cancer therapies. In addition, the knowledge of surface charge density changes at the cancer-surrounding healthy tissue interface may be relevant when redesigning the molecules in chemotherapy and immunotherapy taking into account their polarities. This can also be true in the design of completely novel therapies.
Biogeographic history of Palearctic caudates revealed by a critical appraisal of their fossil record quality and spatio-temporal distribution
Authors: Macaluso Loredana , Mannion Philip D. , Evans Susan E. , Carnevale Giorgio , Monti Sara , Marchitelli Domenico , Delfino Massimo
Published: November 2022

The disjunct geographical range of many lineages of caudates points to a complex evolutionary and biogeographic history that cannot be disentangled by only considering the present-day distribution of salamander biodiversity. Here, we provide a critical reappraisal of the published fossil record of caudates from the Palearctic and quantitatively evaluate the quality of the group's fossil record. Stem-Urodela and Karauridae were widespread in the Palearctic in the Middle Jurassic, suggesting an earlier, unsampled diversification for this group. Cryptobranchidae reached Europe no later than the Oligocene, but this clade was subsequently extirpated from this continent, as well as from western and central Asia. The relatively recent appearance of hynobiids in the fossil record (Early Miocene) is most likely an artefact of a taphonomic bias against the preservation of high-mountain, stream-type environments which early members likely inhabited. Salamandroids first appear in Europe, expanding into Asia by the Miocene. The apparently enigmatic and disjunct distribution of extant caudate lineages is therefore explained by a wider past geographical range, as testified by the fossil record, which was fragmented during the late Cenozoic by a combination of tectonic (i.e. the uplift of the Tibetan Plateau) and climatic drivers, resulting in regional extirpations.
Eco-hydrological modelling of channel network dynamics—part 2: application to metapopulation dynamics
Authors: Bertassello Leonardo E. , Durighetto Nicola , Botter Gianluca
Published: November 2022

Temporal variations in the configuration of the flowing portion of stream networks are observed in the large majority of rivers worldwide. However, the ecological implications of river network expansions/retractions remain poorly understood, owing to the lack of computationally efficient modelling tools conceived for the long-term simulation of river network dynamics. Here, we couple a stochastic approach for the simulation of channel network expansion and retraction (described in a companion paper) with a dynamic version of a stochastic occupancy metapopulation model. The coupled eco-hydrological model is used to analyse the impact of pulsing river networks on species persistence under different hydroclimatic scenarios. Our results unveil the existence of a climate-dependent detrimental effect of network dynamics on species spread and persistence. This effect is enhanced by dry climates, where flashy expansions and retractions of the flowing channels induce metapopulation extinction. Survival probabilities are particularly reduced in settings where the spatial heterogeneity of network connectivity is pronounced. The analysis indicates that accounting for the temporal variability of the flowing river network and its connectivity is a fundamental prerequisite for analysing in-stream metapopulation dynamics.
When wax wanes: competitors for beeswax stabilize rather than jeopardize the honeyguide–human mutualism
Authors: Lloyd-Jones David J. , St Clair James J. H. , Cram Dominic L. , Yassene Orlando , van der Wal Jessica E. M. , Spottiswoode Claire N.
Published: November 2022

Many mutualisms are exploited by third-party species, which benefit without providing anything in return. Exploitation can either destabilize or promote mutualisms, via mechanisms that are highly dependent on the ecological context. Here we study a remarkable bird–human mutualism, in which wax-eating greater honeyguides (Indicator indicator) guide humans (Homo sapiens) to wild bees' nests, in an exchange of knowledge about the location of nests for access to the wax combs inside. We test whether the depletion of wax by mammalian and avian exploiter species either threatens or stabilizes the mutualism. Using camera traps, we monitored feeding visits to wax comb made available following honey harvests. We found that greater honeyguides face competition for wax from conspecifics and nine exploiter species, five of which were not previously known to consume wax. Our results support the hypothesis that heterospecific exploiters stabilize the mutualism, because wax depletion by these competitors probably limits feeding opportunities for conspecific exploiters, favouring the early-arriving individual that guided humans to the bees’ nest. These findings highlight the importance of the ecological context of species interactions and provide further evidence for how mutualisms can persist because of, and not in spite of, exploitation by third-party species.
Partial Activation of PPAR-γ by Synthesized Quercetin Derivatives Modulates TGF-β1-Induced EMT in Lung Cancer Cells
Authors: Ballav Sangeeta , Ranjan Amit , Basu Soumya
Published: November 2022

Non-small cell lung cancer (NSCLC) possess very low survival rate due to poor response to chemotherapy and late detection. Epithelial to mesenchymal transition (EMT) is regarded as a major contributor to drive metastasis during NSCLC progression. Towards this, transforming growth factor-beta 1 (TGF-β1) is the key driver that endows cancer cells with increased aggressiveness. Recently, our group synthesized a series of Schiff base quercetin derivatives (QDs) and ascertained their effectiveness on EMT markers of A549 cell line. Our study evidenced that EMT process was counteracted via the partial activation of a nuclear hormone receptor, Peroxisome proliferator-activated receptor (PPAR)-γ through QDs. Hence, here we extended our work to investigate the interplay between PPAR-γ partial activation by synthesized QDs, TGF-β1-induced EMT and migration in human lung cancer A549 cells. The results revealed that TGF-β1 played a critical role in suppressing PPAR-γ, which was markedly reversed and increased by partial agonists; QUE2FH and QUESH at both protein and transcriptional level. Compared to full agonists, rosiglitazone could not elevate PPAR-γ expression in the presence of TGF-β1 and had negligible effect on translocation of PPAR-γ to nucleus. The partial agonists not only stimulated PPAR-γ in balanced manner but also prevented the loss of E-cadherin and acquisition of TGF-β1-induced mesenchymal markers (Snail, Slug, Vimentin and Zeb-1). Subsequently, the effects were accompanied by attenuation of TGF-β1-induced migratory ability of A549 cells. Together, with the balanced activation profile of PPAR-γ ligands, our findings suggest that these novel partial agonists may serve as potential anti-cancer agents to impede metastasis.
Natural history of retinitis pigmentosa based on genotype, vitamin A/E supplementation, and an electroretinogram biomarker
Authors: Comander Jason , DiFranco Carol Weigel , Sanderson Kit , Place Emily , Maher Matthew , Zampaglione Erin , Zhao Yan , Huckfeldt Rachel , Bujakowska Kinga , Pierce Eric
Published: November 2022

A randomized clinical trial that began in 1984 was conducted to determine the efficacy of vitamin A and E supplementation to reduce the rate of disease progression in patients with retinitis pigmentosa (RP). Vitamin A was shown to provide benefit while vitamin E had an adverse effect. Although genetic testing was unavailable at that time, banked DNA samples now provide the opportunity to combine modern genetic classifications with this extensively phenotyped longitudinal cohort. We hypothesized that the beneficial effects of vitamin A would vary by genetic subtype, and that the electroretinogram (ERG) 30Hz cone flicker implicit time could serve as a biomarker to predict disease progression. Existing genetic solutions or usable DNA samples were available for 96% of subjects. The overall genetic solution rate was 587/765 (77%) of sequenced samples. Combining genetic solutions with ERG outcomes produced a coherent dataset describing the natural history of RP among patients with multiple genetic causes of disease. There were systematic differences in severity and progression seen among different genetic subtypes of RP, confirming and extending findings made for disease caused by mutations in the most common causative genes, includingUSH2A, RHO, RPGR, PRPF31, andEYS. Baseline 30Hz flicker implicit time was a strong predictor of progression rate. Analyses using additional data from the original trial in combination with using the implicit time as a predictive biomarker showed the deleterious effect of vitamin E on progression was still present, but surprisingly found that the effect of vitamin A progression in the cohort as a whole was not detectable. Adding additional subjects from later trials to increase power gave similar results. Subgroup analyses among the largest gene groups revealed a potential adverse effect of vitamin A supplementation in patients with disease due to mutations in theUSH2Agene and a trend toward benefit in patients with the p.Pro23His mutation in theRHOgene, based only on small groups. This study also demonstrated how genetic subtype and implicit time have significant predictive power for a patient’s rate of progression, which is useful prognostically. Validation of implicit time as a biomarker of disease progression, as demonstrated in this large cohort, may help with subject selection and endpoint selection in clinical trials for future experimental therapies. While vitamin E supplementation should still be avoided, these data do not support a generalized neuroprotective effect of vitamin A for all types of RP.
Rethinking Transfer Learning for Medical Image Classification
Authors: Peng Le , Liang Hengyue , Luo Gaoxiang , Li Taihui , Sun Ju
Published: November 2022

Transfer learning (TL) from pretrained deep models is a standard practice in modern medical image classification (MIC). However, what levels of features to be reused are problem-dependent, and uniformly finetuning all layers of pretrained models may be suboptimal. This insight has partly motivated the recentdifferentialTL strategies, such as TransFusion (TF) and layer-wise finetuning (LWFT), which treat the layers in the pretrained models differentially. In this paper, we add one more strategy into this family, calledTruncatedTL, which reuses and finetunes appropriate bottom layers and directly discards the remaining layers. This yields not only superior MIC performance but also compact models for efficient inference, compared to other differential TL methods. Our code is available at:https://github.com/sun-umn/TTL.
Exploring the longitudinal associations of functional network connectivity and psychiatric symptom changes in youth
Authors: Dall’Aglio Lorenza , Estévez-López Fernando , López-Vicente Mónica , Xu Bing , Agcaoglu Oktay , Boroda Elias , Lim Kelvin O. , Calhoun Vince D. , Tiemeier Henning , Muetzel Ryan L.
Published: November 2022

Background

Functional connectivity has been associated with psychiatric problems, both in children and adults, but inconsistencies are present across studies. Prior research has mostly focused on small clinical samples with cross-sectional designs.

Methods

We adopted a longitudinal design with repeated assessments to investigate associations between functional network connectivity (FNC) and psychiatric problems in youth (9- to 17-year-olds) from the general population. The largest single-site study of pediatric neurodevelopment was used: Generation R (N= 3,131). Psychiatric symptoms were measured with the Child Behavioral Checklist as broadband internalizing and externalizing problems, and its eight specific syndrome scales (e.g., anxious-depressed). FNC was assessed with two complementary approaches. First, static FNC (sFNC) was measured with graph theory-based metrics. Second, dynamic FNC (dFNC), where connectivity is allowed to vary over time, was summarized into 5 states that participants spent time in. Cross-lagged panel models were used to investigate the longitudinal bidirectional relationships of sFNC with internalizing and externalizing problems. Similar cross-lagged panel models were run for dFNC.

Results

Small longitudinal relationships between dFNC and certain syndrome scales were observed, especially for baseline syndrome scales (i.e., rule-breaking, somatic complaints, thought problems, and attention problems) predicting connectivity changes. However, no association between any of the psychiatric problems (broadband and syndrome scales) with either measure of FNC survived correction for multiple testing.

Conclusion

We found no or very modest evidence for longitudinal associations between psychiatric problems with dynamic and static FNC in this population-based sample. Differences in findings may stem from the population drawn, study design, developmental timing and sample sizes.
Association of childhood vaccination with family planning, healthcare access, and women education: analysis of Nepal, Senegal and Zambia
Authors: Castillo-Zunino Francisco , Hester Kyra A , Keskinocak Pinar , Nazzal Dima , Freeman Matthew C
Published: November 2022

Background Childhood vaccination, family planning, healthcare access, and women's empowerment are goals targeted by the Sustainable Development Goals (SDG). Barriers to healthcare access impede vaccination, and tackling goals holistically could create larger gains than siloed efforts. We studied Nepal, Senegal, and Zambia to test the association between childhood vaccinations and other SDG indicators to identify clustered deprivations. We quantified how children with few - or no - vaccines and their mothers were vulnerable in other SDG areas. Methods We analyzed Demographic and Health Surveys (DHS) from Nepal, Senegal, and Zambia. Through ordinal logistic regressions, controlling for household/mother's characteristics, we identified strong predictors of the number of vaccine doses one-year-old children received. Through bootstrapping and optimal propensity scores matching, we compared children with no or few childhood doses (0-2 doses in early 2000s, or 0-4 in late 2010s) to children who received eight doses (DTP1-3, MVC1, Pol1-3, and BCG vaccines). Findings Mothers of children who received eight doses were 14-30% more likely than mothers of children with few or no doses to have accessed a health facility in the last year (95% CIs were 16-44% in Nepal 2001, -5% to 33% Nepal 2016, 3-26% Senegal 2005, 1-31% Senegal 2019, 9-38% Zambia 2001-02, 7-36% Zambia 2018), knew on average 0.7-1.5 more contraceptive methods (0.9-2.0 Nepal 2005, 0.1-1.5 Nepal 2016, 0.6-1.7 Senegal 2005, 0.2-1.7 Senegal 2019, 0.1-1.4 Zambia 2001-02, 0.5-1.4 Zambia 2018), and had 10-22% higher literacy rates (12-32% Nepal 2001, -7% to 36% Nepal 2016, 10-26% Senegal 2005, -3 to 22% Senegal 2019, -4% to 28% Zambia 2001-02, 5-36% Zambia 2018). Interpretation Children with few or no vaccine doses and their mothers were behind in access to family planning, healthcare, and education compared to fully vaccinated children and their mothers. Such differences can further impede immunizations; therefore, integrated education and health services are needed to improve vaccination outcomes.
Streptococcus pyogenescolonization in children aged 24-59 months in The Gambia: Impact of Live Attenuated Influenza Vaccine and associated serological responses
Authors: Keeley Alexander J. , Groves Danielle , Armitage Edwin P. , Senghore Elina , Jagne Ya Jankey , Sallah Hadijatou J. , Drammeh Sainabou , Angyal Adri , Hornsby Hailey , de Crombrugghe Gabrielle , Smeesters Pierre , Rossi Omar , Carducci Martina , Peno Chikondi , Bogaert Debby , Kampmann Beate , Marks Michael , Shaw Helen A. , Turner Claire E. , de Silva Thushan I.
Published: November 2022

Background

Immunity toStreptococcus pyogenesin high burden settings is poorly understood. We exploredS. pyogenesnasopharyngeal colonization after intranasal live attenuated influenza vaccine (LAIV) among Gambian children aged 24-59 months, and resulting serological response to 7 antigens.

Methods

A post-hoc analysis was performed in 320 children randomized to receive LAIV at baseline (LAIV group) or not (control).S. pyogenescolonization was determined by quantitative Polymerase Chain Reaction (qPCR) on nasopharyngeal swabs from baseline (D0), day 7 (D7) and day 21 (D21). Anti-streptococcal IgG was quantified, including a subset with paired serum pre/postS. pyogenesacquisition.

Results

The point prevalence ofS. pyogenescolonization ranged from 7-13%. In children negative at D0,S. pyogeneswas detected at D7 or D21 in 18% of LAIV group and 11% of control group participants (p=0.12). The odds ratio (OR) for colonization over time was significantly increased in the LAIV group (D21 vs D0 OR 3.18, p=0.003) but not in the control group (OR 0.86, p=0.79). The highest IgG increases following asymptomatic colonization were seen for M1 and SpyCEP proteins.

Conclusions

AsymptomaticS. pyogenescolonization appears modestly increased by LAIV, and may be immunologically significant. LAIV could be used to study influenza-S. pyogenesinteractions.
A Multi-Laboratory Evaluation of Commercial Monkeypox Molecular Tests
Authors: Erster Oran , Levy Itzchak , Kabat Areej , Menasheh Batya , Levy Virginia , Assraf Hadar , Azar Roberto , Ben-Zvi Haim , Bridenstein Rita , Bondar Olga , Fadeela Ayman , Keren-Naus Ayelet , Peretz Avi , Roif-Kaminsky Diana , Saleh Lolu , Schreiber Lisita , Schwartz Orna , Shaked Pninit , Sorek Nadav , Strauss Merav , Steinberg Rachel , Treygerman Orit , Zisman-Rozen Simona , Yshai Ruth , Tejman-Yarden Noa , Mendelson Ella , Sofer Danit
Published: November 2022

In this report, we describe the first national scale multi-laboratory evaluation of commercial quantitative PCR kits for detection of Monkeypox virus (MPXV) DNA. The objective of this study was to assess the performance of two kits by different diagnostic laboratories across Israel. A panel of 10 standardized samples was tested simultaneously using the Novaplex (15 laboratories) and Bio-Speedy (seven laboratories) kits. An in-house assay based on previously published tests was used as reference. Comparison of the results showed high intra-assay consistency between laboratories, with small variations for most samples.

The sensitivity of the two kits was similar to that of the in-house assay, with an analytical detection limit of less than ten copies per reaction. Significant differences were observed, however, in the Cq values and relative fluorescence (RF), between the assays. The RF signal of the in-house and Bio-Speedy assay ranged between 5,000 and 10,000 RFU, while the signal in the Novaplex assay was less than 600 RFU. Due to the kit measurement protocol, the Cq values of the Bio-Speedy kit were 5-7.5 cycles lower than those of the In-house assay. On the contrary, the Cq values of the Novaplex kit were significantly higher than those of the in-house assay, with differences of 3-5 cycles per sample.

Our results suggest that while all assays were similar in their overall sensitivity, direct comparison of Cq values between them may be misleading. Additionally, the low fluorescence obtained with the Novaplex kit may be problematic with marginal or “noisy” samples. Diagnostic laboratories should therefore consider all these aspects when choosing a specific MPX detection assay.
Handheld chromatic pupillometry can reliably detect functional glaucomatous damage in eyes with high myopia
Authors: Finkelstein Maxwell T. , Nongpiur Monisha E. , Husain Rahat , Perera Shamira A. , Baskaran Mani , Wong Tina T , Aung Tin , Milea Dan , Najjar Raymond P.
Published: November 2022

Purpose

To assess pupillary light responses (PLRs) in eyes with high myopia and evaluate the ability of handheld chromatic pupillometry (HCP) to identify glaucomatous functional loss in eyes with high myopia.

Design

Cross-sectional study with prospective data collection.

Methods

Participants included 28 emmetropes (EM), 24 high myopes without glaucoma (HM), and 17 high myopes with confirmed glaucoma (HMG), recruited at the Singapore National Eye Center. Monocular PLRs were evaluated using a custom-built handheld pupillometer that recorded changes in horizontal pupil radius in response to 9 seconds of exponentially increasing blue (469.1nm) and red (640.1nm) lights. Fifteen pupillometric features were compared between groups. A logistic regression model (LRM) was used to distinguish HMG eyes from non-glaucomatous eyes (EM and HM).

Results

All pupillometric features were similar between EM and HM groups. Phasic constriction to blue (P<0.001) and red (P=0.006) lights, and maximum constriction to blue light (P<0.001) were reduced in HMG compared to EM and HM. Pupillometric features of melanopsin function (PIPR AUC 0-12s (P<0.001) and PIPR 6s (P=0.01) to blue light) were reduced in HMG. Using only three pupillometric features, the LRM could classify glaucomatous from non-glaucomatous eyes with an AUC of 0.89 (95%CI: 0.77–1.00), sensitivity 94.1% (82.4%–100.0%) and specificity 78.8% (67.3%–90.4%).

Conclusions

PLRs to ramping-up light stimuli are unaltered in highly myopic eyes without other diagnosed ocular conditions. Conversely, HCP can distinguish glaucomatous functional loss in highly myopic eyes and may be a useful tool to detect/confirm the presence of glaucoma in patients with high myopia.
Evolving SARS-CoV-2 virulence among hospital and university affiliates in Spain and Greater Boston
Authors: Amer Fares , Lan Fan-Yun , Gil-Conesa Mario , Sidossis Amalia , Bruque Daniel , Iliaki Eirini , Buley Jane , Nathan Neetha , Bruno-Murtha Lou Ann , Carlos Silvia , Kales Stefanos N. , Fernandez-Montero Alejandro
Published: November 2022

Background

The COVID-19 pandemic caused by the SARS-CoV-2 virus greatly affected healthcare workers and healthcare systems. It also challenged schools and universities worldwide negatively affecting in-person education. We conducted this study is to assess the evolution of SARs-CoV-2 virulence over the course of the pandemic.

Methods

A combined cohort of affiliates from the University of Navarra, two hospitals in Spain, and one healthcare system in the Greater Boston area was followed prospectively from March 8th, 2020, to January 31st, 2022 for diagnosis with COVID-19 by PCR testing and related sequelae. Follow-up time was divided into four periods according to distinct waves of infection during the pandemic. Severity of COVID-19 was measured by case-hospitalization rate. Descriptive statistics and multivariable-adjusted statistics using the Poisson mixed-effects regression model were applied.

Results

For the last two periods of the study (January 1stto December 15th, 2021 and December 16th, 2021 to January 31st, 2022) and relative to the first period (March 8thto May 31st, 2020), the incidence rate ratios (IRRs) of hospitalization were 0.08 (95% CI, 0.03-0.17) and 0.03 (95% CI, 0.01-0.15), respectively.

Interpretation

The virulence of COVID-19 and immunity of our populations evolved over time, resulting in a decrease in case severity. We found the case-hospitalization rate decreased more than 90% in our cohort despite an increase in incidence.
Exploring Views of Technology to Inform Maternal and Child Health Interventions for Black Birthing People
Authors: Jaeke Elisha , Olson Jessica , Blackwell Dalvery , Aboagye Sophia , Taylor Reiauna , Zusevics Kaija L , Stolley Melinda
Published: November 2022

Background

Black birthing people experience disproportionately higher rates of morbidity and mortality, and poorer infant health outcomes than all other racial and ethnic groups. Statewide in Wisconsin, an alarming disparity exists between Black and Non-Hispanic White (NHW) breastfeeding initiation rates (54% and 87%, respectively). For the last fourteen years, the African American Breastfeeding Network (AABN) has operated in Milwaukee County, where 70% of the state’s Black population lives. AABN’s mission is to improve maternal health and champion breastfeeding equity for Black birthing families. In 2018, AABN received more referrals than could be served by their team of doulas, lactation consultants, and advocates, leading our team to pursue ways to expand their reach through technology-based approaches. With the onset of COVID-19, the need for telehealth support increased drastically, as referrals for AABN services tripled. In this study, we explore the use of technology to support Black birthing families in Wisconsin and beyond, in the hopes of expanding the capacity of organizations like AABN.

Methods

A survey was conducted amongst 21 Black women who were pregnant or had given birth in the last year, regarding perceptions of technology. Women were split equally into three focus groups to discuss survey results further and provide context. Focus groups were recorded, transcribed, and coded for themes.

Results

Participants were “Likely” to use their phone or the internet to look for general or health-related information, but only “Somewhat Likely” to trust either general or health-related information. Participants were “Somewhat Likely” to trust the information on the phone or the internet as much as their healthcare provider (doctor, nurse, doula) in person. In the focus groups, all participants agreed that the phone or the internet was the first place looked to for information, ahead of consulting a healthcare professional. A comprehensive list of desired features was generated to guide the development of a resource to support AABN.

Conclusions

Study findings support exploring mobile technology-based approaches for breastfeeding support and education. Participants emphasized that to be relevant for them, a telehealth resource would need to: 1) Build meaningful connections between patients and providers, 2) Treat diverse opinions with trust and respect, and 3) Offer multiple sources and formats for information that can be easily cross-referenced.
Machine Learning for Antibiotic Stewardship in the Treatment of Stapholycoccus Bacterial Infections
Authors: Brokowski Trevor J. , Chiang Jeffrey N.
Published: November 2022

Antibiotic resistance is one of the leading issues in modern healthcare due to the inability to treat common infections with available antibiotics. Many of the mechanisms of resistance have been caused by the inappropriate prescription of antibiotics to treat illnesses such as the cold or flu or the over-prescription of broad-spectrum antibiotics. Epitomizing this problem is the Staphylococcus bacteria where certain strains have become resistant to penicillin-related drugs and Vancomycin, one of the treatments for MRSA. To address this, we developed machine learning models to predict antibiotic activity and susceptibility using a patient’s entire available electronic health record. We selected patients who were suspected of having a staph infection from the Medical Information Mart for Intensive Care III (MIMIC-III) data set and utilized their microbiological culture results to identify the number of patients that were prescribed an inappropriate antibiotic and then propose suitable alternatives. In our test set, we identified that empiric prescriptions had an efficiency rate of 40 percent (the rate at which an antibiotic that would provide activity was prescribed), and the other 60 percent of cases were not susceptible to the prescribed antibiotic or the antibiotic that they were given was not tested for susceptibility against their infection. Our best models identified antibiotic susceptibility with AUROCs up to 0.9 and raw specificity up to 0.7. The models were also able to propose suitable alternatives in all but 10 cases. Overall these results demonstrate the need for implementing clinical decision support systems advising clinicians during the prescription process, and our further work will address this issue.
Persistent alveolar type 2 dysfunction and lung structural derangement in post-acute COVID-19
Authors: Rendeiro André F. , Ravichandran Hiranmayi , Kim Junbum , Borczuk Alain C. , Elemento Olivier , Schwartz Robert E.
Published: November 2022

SARS-CoV-2 infection can manifest as a wide range of respiratory and systemic symptoms well after the acute phase of infection in over 50% of patients. Key questions remain on the long-term effects of infection on tissue pathology in recovered COVID-19 patients. To address these questions we performed multiplexed imaging of post-mortem lung tissue from 12 individuals who died post-acute COVID-19 (PC) and compare them to lung tissue from patients who died during the acute phase of COVID-19, or patients who died with idiopathic pulmonary fibrosis (IPF), and otherwise healthy lung tissue. We find evidence of viral presence in the lung up to 359 days after the acute phase of disease, including in patients with negative nasopharyngeal swab tests. The lung of PC patients are characterized by the accumulation of senescent alveolar type 2 cells, fibrosis with hypervascularization of peribronchial areas and alveolar septa, as the most pronounced pathophysiological features. At the cellular level, lung disease of PC patients, while distinct, shares pathological features with the chronic pulmonary disease of IPF. which may help rationalize interventions for PC patients. Altogether, this study provides an important foundation for the understanding of the long-term effects of SARS-CoV-2 pulmonary infection at the microanatomical, cellular, and molecular level.