bluuebunny/crossref_metadata_2025 huggingface dataset:
Improvement of 1-Stage Comprehensive Operation Technique for Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome
Authors: Zhao Mingyu , Wu Lehao , Li Wuyan , Wang Qianwen , Wang Tailing , Wang Jiaqi
Published: August 2023

Background:

This retrospective case series presents the clinical results of a modified 1-stage comprehensive surgical method for blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).

Methods:

A total of 25 patients with BPES underwent a modified reverse Z-plastic surgery method to bisect the epicanthus into 2 unequal V-shaped flaps and suture them alternately. The medial canthus ligament was partially incised, shortened, and sutured; the outer canthus was opened with a V-Y flap. The gray line of the outer canthus was cut to extend the eyelid margin length. Ptosis was corrected using the orbicularis oculi–frontalis composite flap technique. We studied the inner intercanthal distance (IICD), interpupillary distance (IPD), horizontal palpebral fissure length (HPFL), marginal reflex distance 1 (MRD-1), IICD/IPD ratio, IICD/HPFL ratio, Vancouver Scar Scale, and overall postoperative satisfaction.

Results:

The 25 patients included 12 girls and 13 boys (mean age, 8.3 ± 6.8 years), 19 of whom had a family history of BPES. The mean IPD value was 50.15 ± 7.43 mm. IICD decreased from 39.38 ± 2.39 mm preoperatively to 31.64 ± 2.37 mm postoperatively, IICD/IPD from 0.8 ± 0.1 preoperatively to 0.6 ± 0.1 postoperatively (P < 0.05), and IICD/HPFL from 1.98 ± 0.33 preoperatively to 1.22 ± 0.10 postoperatively (P < 0.01). HPFL increased from 20.08 ± 3.53 mm preoperatively to 26.04 ± 1.36 mm postoperatively (P < 0.01), and MRD-1 from −1.12 ± 0.71 mm preoperatively to 3.24 ± 0.47 mm postoperatively (P < 0.01). The postoperative Vancouver Scar Scale score was 3.68 ± 1.07. Patient satisfaction was rated as 8.8 ± 1.08, with a relatively high overall satisfaction rate.

Conclusions:

The corrective effect on BPES was noticeable, improving the IICD/HPFL and IICD/IPD ratios. Postoperative scars were not evident, and patient satisfaction was high.

CLINICAL QUESTION/LEVEL OF EVIDENCE:

Therapeutic, IV.
Divergent Findings in the Diagnosis of ATTR-CM Using Common Cardiac Diagnostics and 99mTc-DPD Scintigraphy
Authors: Kunte Sophie C. , Schwarting Stéphanie K. , Holzgreve Adrien , Wöhrle Caroline , Unterrainer Marcus , Bartenstein Peter , Unterrainer Lena M.
Published: August 2023

A 77-year-old man presented with progressive deterioration of physical capacity after successful percutaneous coronary intervention of known chronic coronary syndrome. Transthoracic echocardiography revealed hypertrophy of the left ventricle, and electrocardiogram showed low QRS voltage in all leads. 99mTc-DPD scintigraphy was conducted to differentiate etiology such as amyloidosis and revealed increased cardiac tracer uptake in the left (grade 3) and right ventricle. Immunofixation showed no signs of paraproteinemia or Bence-Jones proteinuria. Thus, biventricular involvement of ATTR-cardiomyopathy was identified by 99mTc-DPD scintigraphy. This approach should be considered if hypertrophic phenotype is present in patients with persistent deterioration of physical capacity not attributable to coronary artery disease.
Decreased Utilization Rate of Grafts for Liver Transplantation After Implementation of Acuity Circle–based Allocation
Authors: Bekki Yuki , Myers Bryan , Tomiyama Koji , Imaoka Yuki , Akabane Miho , Kwong Allison J. , Melcher Marc L. , Sasaki Kazunari
Published: August 2023

Background.

The allocation system for livers began using acuity circles (AC) in 2020. In this study, we sought to evaluate the impact of AC policy on the utilization rate for liver transplantation (LT).

Methods.

Using the US national registry data between 2018 and 2022, LTs were equally divided into 2 eras: pre-AC (before February 4, 2020) and post-AC (February 4, 2020, and after). Deceased potential liver donors were defined as deceased donors from whom at least 1 organ was procured.

Results.

The annual number of deceased potential liver donors increased post-AC (from 10 423 to 12 259), approaching equal to that of new waitlist registrations for LT (n = 12 801). Although the discard risk index of liver grafts was comparable between the pre- and post-AC eras, liver utilization rates in donation after brain death (DBD) and donation after circulatory death (DCD) donors were lower post-AC (P < 0.01; 79.8% versus 83.4% and 23.7% versus 26.0%, respectively). Recipient factors, ie, no recipient located, recipient determined unsuitable, or time constraints, were more likely to be reasons for nonutilization after implementation of the AC allocation system compared to the pre-AC era (20.0% versus 12.3% for DBD donors and 50.1% versus 40.8% for DCD donors). Among non–high-volume centers, centers with lower utilization of marginal DBD donors or DCD donors were more likely to decrease LT volume post-AC.

Conclusions.

Although the number of deceased potential liver donors has increased, overall liver utilization among deceased donors has decreased in the post-AC era. To maximize the donor pool for LT, future efforts should target specific reasons for liver nonutilization.
Bat activity correlated with migratory insect bioflows in the Pyrenees
Authors: Hawkes Will L. , Davies Kelsey , Weston Scarlett , Moyes Kelly , Chapman Jason W. , Wotton Karl R.
Published: August 2023

High altitude mountain passes in the Pyrenees are known to be important migratory hotspots for autumn migrating insects originating from large swathes of northern Europe. In the Pyrenees, prior research has focused on diurnal migratory insects. In this study, we investigate the nocturnal component of the migratory assemblage and ask if this transient food source is also used by bat species. Three seasons of insect trapping revealed 66 species of four different orders, 90% of which were Noctuid moths, including the destructive pestHelicoverpa armigera, otherwise known as the cotton bollworm. Acoustic bat detectors revealed that high activity ofNyctalusspp. andTadarida teniotisbats were closely synchronized with the arrival of the migratory moths, suggesting this food source is important for both resident and migratory bats to build or maintain energy reserves. Bats of theNyctalusspp.are likely migrating through the study site using fly-and-forage strategies or stopping over in the area, while residentT. teniotismay be exploiting the abundant food source to build fat stores for hibernation. This study shows that nocturnal migratory insects are abundant in the Pyrenees during autumn and interact during migration, not only with their co-migrant bats but also with resident bat species.
Intrinsic and extrinsic drivers of shape variation in the albatross compound bill
Authors: Tyler Joshua , Hocking David P. , Younger Jane L.
Published: August 2023

Albatross are the largest seabirds on Earth and have a suite of adaptations for their pelagic lifestyle. Rather than having a bill made of a single piece of keratin, Procellariiformes have a compound rhamphotheca, made of several joined plates. Drivers of the shape of the albatross bill have not been explored. Here we use three-dimensional scans of 61 upper bills from 12 species of albatross to understand whether intrinsic (species assignment & size) or extrinsic (diet) factors predict bill shape. Diet is a significant predictor of bill shape with coarse dietary categories providing higher
R
2
values than dietary proportion data. We also find that of the intrinsic factors, species assignment accounts for ten times more of the variation than size (72% versus 6.8%) and that there is a common allometric vector of shape change between all species. When considering species averages in a phylogenetic framework, there are significant Blomberg's
K
results for both shape and size (
K
= 0.29 & 1.10) with the first axis of variation having a much higher
K
value (
K
= 1.9), reflecting the split in shape at the root of the tree. The influence of size on bill shape is limited, with species assignment and diet predicting far more of the variation. The results show that both intrinsic and extrinsic factors are needed to understand morphological evolution.
Multi-locus genomic signatures of local adaptation to snow across the landscape in California populations of a willow leaf beetle
Authors: Keller Abigail G. , Dahlhoff Elizabeth P. , Bracewell Ryan , Chatla Kamalakar , Bachtrog Doris , Rank Nathan E. , Williams Caroline M.
Published: August 2023

Organisms living in mountains contend with extreme climatic conditions, including short growing seasons and long winters with extensive snow cover. Anthropogenic climate change is driving unprecedented, rapid warming of montane regions across the globe, resulting in reduced winter snowpack. Loss of snow as a thermal buffer may have serious consequences for animals overwintering in soil, yet little is known about how variability in snowpack acts as a selective agent in montane ecosystems. Here, we examine genomic variation in California populations of the leaf beetle
Chrysomela aeneicollis
, an emerging natural model system for understanding how organisms respond to climate change. We used a genotype–environment association approach to identify genomic signatures of local adaptation to microclimate in populations from three montane regions with variable snowpack and a coastal region with no snow. We found that both winter-associated environmental variation and geographical distance contribute to overall genomic variation across the landscape. We identified non-synonymous variation in novel candidate loci associated with cytoskeletal function, ion transport and membrane stability, cellular processes associated with cold tolerance in other insects. These findings provide intriguing evidence that variation in snowpack imposes selective gradients in montane ecosystems.
Immune challenge reduces daily activity period in free-living birds for three weeks
Authors: Lennon Rosie J. , Ronanki Shivani , Hegemann Arne
Published: August 2023

Non-lethal infections are common in free-living animals and the associated sickness behaviours can impact crucial life-history trade-offs. However, little is known about the duration and extent of such sickness behaviours in free-living animals, and consequently how they affect life-history decisions. Here, free-living Eurasian blackbirds,
Turdus merula
, were immune-challenged with lipopolysaccharide (LPS) to mimic a bacterial infection and their behaviour was monitored for up to 48 days using accelerometers. As expected, immune-challenged birds were less active than controls within the first 24 h. Unexpectedly, this reduced activity remained detectable for 20 days, before both groups returned to similar activity levels. Furthermore, activity was positively correlated with a pre-experimental index of complement activity, but only in immune-challenged birds, suggesting that sickness behaviours are modulated by constitutive immune function. Differences in daily activity levels stemmed from immune-challenged birds resting earlier at dusk than control birds, while activity levels between groups were similar during core daytime hours. Overall, activity was reduced by 19% in immune-challenged birds and they were on average almost 1 h less active per day for 20 days. This unexpected longevity in sickness behaviour may have severe implications during energy-intense annual-cycle stages (e.g. breeding, migration, winter). Thus, our data help to understand the consequences of non-lethal infections on free-living animals.
Pervasive genotype-by-environment interactions shape the fitness effects of antibiotic resistance mutations
Authors: Soley Jake K. , Jago Matthew , Walsh Calum J. , Khomarbaghi Zahra , Howden Benjamin P. , Lagator Mato
Published: August 2023

The fitness effects of antibiotic resistance mutations are a major driver of resistance evolution. While the nutrient environment affects bacterial fitness, experimental studies of resistance typically measure fitness of mutants in a single environment only. We explored how the nutrient environment affected the fitness effects of rifampicin-resistant
rpoB
mutations in
Escherichia coli
under several conditions critical for the emergence and spread of resistance—the presence of primary or secondary antibiotic, or the absence of any antibiotic. Pervasive genotype-by-environment (GxE) interactions determined fitness in all experimental conditions, with rank order of fitness in the presence and absence of antibiotics being strongly dependent on the nutrient environment. GxE interactions also affected the magnitude and direction of collateral effects of secondary antibiotics, in some cases so drastically that a mutant that was highly sensitive in one nutrient environment exhibited cross-resistance to the same antibiotic in another. It is likely that the mutant-specific impact of
rpoB
mutations on the global transcriptome underpins the observed GxE interactions. The pervasive, mutant-specific GxE interactions highlight the importance of doing what is rarely done when studying the evolution and spread of resistance in experimental and clinical work: assessing fitness of antibiotic-resistant mutants across a range of relevant environments.
The evolutionary ecology of fungal killer phenotypes
Authors: Travers-Cook Thomas J. , Jokela Jukka , Buser Claudia C.
Published: August 2023

Ecological interactions influence evolutionary dynamics by selecting upon fitness variation within species. Antagonistic interactions often promote genetic and species diversity, despite the inherently suppressive effect they can have on the species experiencing them. A central aim of evolutionary ecology is to understand how diversity is maintained in systems experiencing antagonism. In this review, we address how certain single-celled and dimorphic fungi have evolved allelopathic killer phenotypes that engage in antagonistic interactions. We discuss the evolutionary pathways to the production of lethal toxins, the functions of killer phenotypes and the consequences of competition for toxin producers, their competitors and toxin-encoding endosymbionts. Killer phenotypes are powerful models because many appear to have evolved independently, enabling across-phylogeny comparisons of the origins, functions and consequences of allelopathic antagonism. Killer phenotypes can eliminate host competitors and influence evolutionary dynamics, yet the evolutionary ecology of killer phenotypes remains largely unknown. We discuss what is known and what remains to be ascertained about killer phenotype ecology and evolution, while bringing their model system properties to the reader's attention.
Pulmonary Artery Pressures and Mortality during VA ECMO: An ELSO Registry Analysis
Authors: Owyang Clark G. , Rippon Brady , Teran Felipe , Brodie Daniel , Araos Joaquin , Burkhoff Daniel , Kim Jiwon , Tonna Joseph E.
Published: August 2023

Background

Systemic hemodynamics and specific ventilator settings have been shown to predict survival during venoarterial extracorporeal membrane oxygenation (VA ECMO). While these factors are intertwined with right ventricular (RV) function, the independent relationship between RV function and survival during VA ECMO is unknown.

Objectives

To identify the relationship between RV function with mortality and duration of ECMO support.

Methods

Cardiac ECMO runs in adults from the Extracorporeal Life Support Organization (ELSO) Registry between 2010 and 2022 were queried. RV function was quantified via pulmonary artery pulse pressure (PAPP) for pre-ECMO and on-ECMO periods. A multivariable model was adjusted for Society for Cardiovascular Angiography and Interventions (SCAI) stage, age, gender, and concurrent clinical data (i.e., pulmonary vasodilators and systemic pulse pressure). The primary outcome was in-hospital mortality.

Results

A total of 4,442 ECMO runs met inclusion criteria and had documentation of hemodynamic and illness severity variables. The mortality rate was 55%; non-survivors were more likely to be older, have a worse SCAI stage, and have longer pre-ECMO endotracheal intubation times (P < 0.05 for all) than survivors. Improving PAPP from pre-ECMO to on-ECMO time (Δ PAPP) was associated with reduced mortality per 10 mm Hg increase (OR: 0.91 [95% CI: 0.86-0.96]; P=0.002). Increasing on-ECMO PAPP was associated with longer time on ECMO per 10 mm Hg (Beta: 15 [95% CI: 7.7-21]; P<0.001).

Conclusions

Early improvements in RV function from pre-ECMO values were associated with mortality reduction during cardiac ECMO. Incorporation of Δ PAPP into risk prediction models should be considered.
Comprehensive identification of potentially functional genes for transposon mobility in theC. elegansgenome
Authors: Arata Yukinobu , Jurica Peter , Parrish Nicholas , Sako Yasushi
Published: August 2023

Transposons are mobile DNA elements that encode genes for their own mobility. Whereas transposon copies accumulate on the genome during evolution, many lose their mobile activity due to mutations. Here, we focus on transposon-encoded genes that are directly involved in the replication, excision, and integration of transposon DNA, which we refer to as “transposon-mobility genes”, in theCaenorhabditis elegansgenome. Among the 62,773 copies of retro- and DNA transposons in the latest assembly of theC. elegansgenome (VC2010), we found that the complete open reading frame structure was conserved in 290 transposon-mobility genes. Critical amino acids at the catalytic core were conserved in only 145 of these 290 genes. Thus, in contrast to the huge number of transposon copies in the genome, only a limited number of transposons are autonomously mobile. We conclude that the comprehensive identification of potentially functional transposon-mobility genes in all transposon orders of a single species can provide a basis of molecular analysis for revealing the developmental, aging, and evolutionary roles of transposons.
Pregnancy-Associated Bleeding and Genetics: Five Sequence Variants in the Myometrium and Progesterone Signaling Pathway are associated with postpartum hemorrhage
Authors: Westergaard David , Steinthorsdottir Valgerdur , Stefansdottir Lilja , Rohde Palle Duun , Wu Xiaoping , Geller Frank , Tyrmi Jaakko , Havulinna Aki S. , Navais Pol Sole , Flatley Christopher , Ostrowski Sisse Rye , Pedersen Ole Birger , Erikstrup Christian , Sørensen Erik , Mikkelsen Christina , Brun Mie Topholm , Jensen Bitten Aagaard , Brodersen Thorsten , Ullum Henrik ,   FinnGen,   Danish Blood Donor Study Genomic Consortium,   Estonian Biobank Research Team,   Nordic Collaboration for Womens and Reproductive Health, Magnus Per , Andreassen Ole A. , Njolstad Pål R. , Kolte Astrid Marie , Krebs Lone , Nyegaard Mette , Hansen Thomas Folkmann , Fenstra Bjarke , Daly Mark , Lindgren Cecilia M. , Thorleifsson Gudmar , Stefansson Olafur A. , Sveinbjornsson Gardar , Gudbjartsson Daniel F. , Thorsteinsdottir Unnur , Banasik Karina , Jacobsson Bo , Laisk Triin , Laivuori Hannele , Stefansson Kari , Brunak Søren , Nielsen Henriette Svarre
Published: August 2023

Bleeding in early pregnancy and postpartum hemorrhage (PPH) bear substantial risks, with the former closely associated with pregnancy loss and the latter being the foremost cause of maternal death, underscoring the severity of these complications in maternal-fetal health. Here, we investigated the genetic variation underlying aspects of pregnancy-associated bleeding and identified five loci associated with PPH through a meta-analysis of 21,512 cases and 259,500 controls. Functional annotation analysis indicated candidate genes,HAND2,TBX3, andRAP2C/FRMD7,at three loci and showed that at each locus, associated variants were located within binding sites for progesterone receptors (PGR). Furthermore, there were strong genetic correlations with birth weight, gestational duration, and uterine fibroids. Early bleeding during pregnancy (28,898 cases and 302,894 controls) yielded no genome-wide association signals, but showed strong genetic correlation with a variety of human traits, indicative of polygenic and pleiotropic effects. Our results suggest that postpartum bleeding is related to myometrium dysregulation, whereas early bleeding is a complex trait related to underlying health and possibly socioeconomic status.
Lessons learned from operationalizing the integration of nutrition-specific and nutrition-sensitive interventions in rural Ethiopia
Authors: Mersha Girmay Ayana , Tariku Eshetu Zerihun , Boynito Wanzahun Godana , Woldeyohaness Meseret , Wodajo Birhanu , Kebebe Tadese , Henauw Stefaan De , Abbeddou Souheila
Published: August 2023

Background

Undernutrition reduction requires coordinated efforts across sectors to address its causes. A multisectoral approach is important in diagnosing the problem and identifying solutions that would be implemented across different sectors.

The study aims to explore the experience of health and agriculture extension workers in integrating nutrition services provided to households with children under two years of age at community level.

Methods

A qualitative study has been conducted in agrarian areas of Ethiopia in 2021 at the end of a large intervention program to reduce stunting. In total, 28 key informant interviews were conducted with health- and agriculture-extension workers and mothers. A framework analysis approach was applied to manage and analyze data using NVivo version 12 software.

Results

Community-level joint intervention is a feasible approach to integrating nutrition services. Farm gardening and cooking demonstrations were practiced jointly with extension workers and households. Because of service integration, extension workers perceived an improved father’s role in supporting mothers in childcaring and feeding nutritious diets to children, and decreased severe cases of undernutrition. Integration of health and agriculture sectors for nutrition intervention was challenged by the high workload on extension workers, poor supervision and leadership commitment, lack of appropriate agricultural inputs, and absence of clarity on sector-specific roles. In some areas nutrition services are not owned by the health and agriculture sectors, and it was overlooked.

Conclusion

Integrating existing community-level platforms are key entry points to address undernutrition and promote key agriculture and health interventions in Ethiopia. Empowering extension workers through training, monitoring, and supervision is part of ensuring the sustainability of integration between sectors.
Evolution of Myocarditis Incidence at a Large Healthcare System Before and During COVID-19 Pandemic
Authors: Case Brian C. , Waksman Ori , Rappaport Hank , Zhang Cheng , Waksman Ron
Published: August 2023

Background

Myocarditis is a recognized complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Emerging studies further suggest an associated risk of myocarditis following administration of messenger RNA (mRNA) COVID-19 vaccinations. coronavirus disease 2019 (COVID-19) vaccinations. We investigated the incidence of myocarditis throughout the COVID-19 pandemic across a large healthcare system in the Washington, DC, metropolitan area.

Methods

This retrospective analysis of patients admitted from 2017-2022. Myocarditis cases were temporally divided into two cohorts based on year of admission (pre-pandemic 2017-2019; pandemic 2020-2022), which were compared for overall myocarditis incidence. The primary endpoint was in-hospital mortality.

Results

The cohort included 573 myocarditis patients (pre-pandemic=208, pandemic=365). From 2017-2019, the total number and rate of myocarditis cases was consistent. Overall cases of myocarditis increased during the pandemic (97, 126, 142 patients in 2020, 2021, 2022, respectively). Interestingly, the rate of myocarditis cases not related to COVID-19 or the vaccines stayed consistent (0.0674%, 0.0676%, 0.0807%), but the rate of myocarditis related to COVID-19 or the vaccines myocarditis increased each year (0.0210%, 0.0416%, 0.0480%). In-hospital mortality was similar between the two pre-pandemic and pandemic cohorts (5.35% versus 7.7%, 0.276).

Conclusion

Among hospitalized patients, during the COVID-19 pandemic, the incidence of myocarditis increased as compared to the pre-pandemic era. It appears this increase is associated with either the SARS-CoV-2 infection or COVID-19 vaccination. In-hospital outcomes did not differ during the pandemic, but ongoing research is needed to evaluate the long-term impact of myocarditis during the pandemic.
Cardiovascular risk in treated hypertensive patients with isolated diastolic hypertension and isolated low diastolic blood pressure
Authors: Chang Wei-Lun , Chen Ying-Fan , Lee Yu-Hsuan , Shiu Ming-Neng , Chang Po-Yin , Guo Chao-Yu , Huang Chi-Jung , Chiang Chern-En , Chen Chen-Huan , Chuang Shao-Yuan , Cheng Hao-Min
Published: August 2023

Background

The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure (SBP) on major adverse cardiovascular events (MACE) is uncertain. This study examined whether isolated diastolic hypertension (IDH) and isolated low DBP (ILDBP) were associated with MACE in treated patients.

Methods

7582 hypertensive patients with on-treatment SBP <130 mmHg from the Systolic Blood Pressure Intervention Trial (SPRINT) were categorized based on average DBP: <60 mmHg (n=1031; ILDBP), 60–79 mmHg (n=5432), ≥80 mmHg (n=1119; IDH). MACE risk was estimated using Cox proportional hazards models. The analysis was supplemented by a meta-analysis involving 10106 SPRINT and four cohort participants.

Results

Median age of the SPRINT participants was 67.0 years, and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed MACE. The incidence of MACE was 3.9 cases per 100 person-years for ILDBP, 1.9 cases for DBP 60–79 mmHg, and 1.8 cases for IDH. ILDBP was associated with 1.32-fold increased MACE risk (hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.05–1.66), whereas IDH was not (HR: 1.18, 95% CI: 0.87–1.59). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all p-values for interaction >0.05). The meta-analysis indicated increased MACE risk in ILDBP (HR: 1.26, 95% CI: 1.05–1.52) compared with DBP 60–79 mmHg.

Conclusions

In treated patients with normalized SBP, excessively low DBP was associated with increased MACE risk, while IDH was not. Further research is required for ILDBP management.
Effectiveness and cost-effectiveness of a culturally tailored Behavioural Activation intervention (DiaDeM) for treating Depression in Type 2 Diabetes: Protocol for a parallel arm, multi-country, randomised controlled trial in South Asia
Authors: Siddiqui Faraz , Aslam Faiza , Ahmed Naveed , Afaq Saima , Khan Asima , Keding Ada , Walker Simon , Jennings Hannah Maria , Zavala Gerardo A , Ekers David , Fottrell Edward , Hewitt Catherine , Haq Zia Ul , Siddiqi Najma ,   DiaDeM Global Health Research Group
Published: August 2023

Background

The co-occurrence of depression among individuals with type 2 diabetes is a recognised global health problem and can lead to poorer health outcomes for both conditions. Behavioural activation is an evidence-based brief, low-cost psychological therapy which can be delivered by trained non-specialists, and is useful in treating depression, particularly in low-resource settings. The aim of this study is to test the effectiveness and cost-effectiveness of culturally adapted behavioural activation for depression in people with both depression and type 2 diabetes in two South Asian countries - Bangladesh and Pakistan.

Methods

A parallel arm, multi-country randomised controlled trial will be conducted in urban health care facilities providing diabetes services. We will recruit 604 adults in total, and randomise them using a 1:1 allocation ratio to receive culturally adapted behavioural activation (DiaDeM), or optimised usual care. DiaDeM comprises six sessions of behavioural activation with a trained non-mental health facilitator, conducted face-to-face and/or remotely. Optimised usual care includes information on depression, pharmacological and non-pharmacological treatment options for depression and details for accessing help locally. Participants in both arms will be followed up at 6- and 12-months post-randomisation. The primary outcome is the severity of depressive symptoms at 6 months, measured using the 9-item Patient Health Questionnaire (PHQ-9). Secondary outcomes include diabetes control, measured using glycosylated haemoglobin. An embedded process evaluation will evaluate the quality of intervention delivery and explore mechanisms of change and the contextual factors associated with the implementation and observed outcomes of DiaDeM. An economic evaluation will gauge DiaDeM’s cost-effectiveness and estimate the impact of diabetes and depression on economic outcomes.

Conclusion

There is an urgent need to address the rising burden of depression and chronic physical illnesses, such as type 2 diabetes. Interventions such as DiaDeM, which are culturally relevant and rely on a task-sharing approach, offer a potentially low-cost treatment within existing health services. If found to be effective and cost-effective, DiaDeM may be scaled up to address the mental health ‘treatment gap’ and improve mental and physical health outcomes for people with diabetes in South Asia.

Trial registration

ISRCTN40885204. Trial registered on 11th April 2023
Mitigating Pathogenesis for Target Discovery and Disease Subtyping
Authors: Strobl Eric V. , Lasko Thomas A. , Gamazon Eric R.
Published: August 2023

Treatments ideally mitigate pathogenesis, or the detrimental effects of the root causes of disease. However, existing definitions of treatment effect fail to account for pathogenic mechanism. We therefore introduce theTreated Root causal Effects(TRE) metric which measures the ability of a treatment to modify root causal effects. We leverage TREs to automatically identify treatment targets and cluster patients who respond similarly to treatment. The proposed algorithm learns a partially linear causal model to extract the root causal effects of each variable and then estimates TREs for target discovery and down-stream subtyping. We maintain interpretability even without assuming an invertible structural equation model. Experiments across a range of datasets corroborate the generality of the proposed approach.
Comprehensive Analysis of Lung Cancer Classification Using Gaussian Process Classifier: Unveiling Exceptional Performance and Clinical Implications
Authors: Santos Dheiver Francisco
Published: August 2023

In this analysis, the performance of the Gaussian Process Classifier (GPC) was evaluated for classifying instances of lung cancer using various metrics. The GPC model achieved impressive results, with accuracy ranging from approximately 83.87% to 96.67%. Precision values ranged from 75.86% to 96.79%, recall values ranged from 83.87% to 96.67%, and F1-score values ranged from 81.09% to 96.36%. These metrics highlight the GPC model’s exceptional performance in accurately classifying lung cancer cases. The findings from this analysis have significant implications for improving lung cancer diagnosis, treatment planning, and ultimately enhancing patient outcomes.
Sexually dimorphic leading-edge serrations evolved in silent swallows
Authors: Hasegawa Masaru
Published: August 2023

Leading-edge serrations are specialized feather structures, mitigating acoustic noise during foraging flight in owls, and have been extensively studied and applied to man-made noise-reducing structures. Similar structures occur in other avian species, such as swallows, although the ecological functions of the serrations in these species remain unclear. I conducted macroevolutionary analyses of hirundines (subfamily: Hirundininae), in which leading-edge serrations evolved multiple times, to examine their evolution in relation to vocal activity. I found that silent hirundines showed a higher probability of possessing leading-edge serrations, indicating that leading-edge serrations of swallows serve some functions associated with acoustics as in owls. I also found that silent vocal activity accompanied loss of song, a well-known acoustic sexual signal, but not with sexual plumage dimorphism, indicating that not sexual selection in general but sexual selection on acoustic traits matters. These findings explain sexually dimorphic leading-edge serrations, a unique characteristic in these diurnal visually-foraging birds: stealth males rather than noisy males would be favored. Although leading-edge serrations in hirundines would serve acoustic functions like nocturnal birds such as owls, they might serve a unique sexual function.
Risk of opioid-related mortality associated with buprenorphine versus methadone: A systematic review of observational studies
Authors: Lim Jihoon , Farhat Imen , Douros Antonios , Ouizzane Soukaina , Panagiotoglou Dimitra
Published: August 2023

Introduction

Buprenorphine and methadone are effective treatments of opioid use disorder (OUD) and can reduce drug-related mortality. While observational studies have compared head-to-head buprenorphine and methadone, this evidence has not been previously synthesized. Our study aims to systematically review the available evidence on the comparative effectiveness of buprenorphine and methadone in people with OUD, thereby rigorously assessing the methodological quality of individual studies.

Methods

We searched Medline, Embase, PsycINFO, and Web of Science for all relevant articles published between 1978 and April 8, 2023. Observational studies directly comparing the risk of drug-related mortality between buprenorphine and methadone among people with OUD were eligible. We assessed the overall risk of bias using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool.

Results

Our systematic review included seven studies. There was mixed evidence of comparative mortality risk, with heterogeneity across study region, time, and treatment status (on treatment vs. discontinued). Three studies reported no difference, and four reported findings in favour of buprenorphine. Based on ROBINS-I, three studies had a moderate risk of bias, two had a severe risk, and two had a critical risk. Major sources of biases were residual confounding and selection bias along with presence of prevalent user bias, informative censoring, and left truncation.

Conclusions

Due to methodological limitations of the observational studies, generalizability of their findings remains unknown. Therefore, to provide a more accurate comparative safety profile for these two medications, further observational studies with methodological rigour are warranted.
Factors associated with severe acute respiratory syndrome-related coronavirus 2 infection in unvaccinated children and young adults
Authors: Silverberg Sarah L. , Shulha Hennady P. , McMillan Brynn , He Guanyuhui , Lee Amy , Márquez Ana Citlali , Bartlett Sofia R. , Gill Vivek , Abu-Raya Bahaa , Bettinger Julie A. , Cabrera Adriana , Coombs Daniel , Gantt Soren , Goldfarb David M. , Sauvé Laura , Krajden Mel , Morshed Muhammad , Sekirov Inna , Jassem Agatha N. , Sadarangani Manish
Published: August 2023

BACKGROUND

Pediatric COVID-19 cases are often mild or asymptomatic, which has complicated estimations of disease burden using existing testing practices. We aimed to determine the age-specific population seropositivity and risk factors of SARS-CoV-2 seropositivity among children and young adults during the pandemic in British Columbia (BC).

METHODS

We conducted two cross-sectional serosurveys: phase 1 enrolled children and adults <25 years between November 2020-May 2021 and phase 2 enrolled children <10 years between June 2021-May 2022 in BC. Participants completed electronic surveys and self-collected finger-prick dried blood spot (DBS) samples. Samples were tested for immunoglobulin G antibodies against ancestral spike protein (S). Descriptive statistics from survey data were reported and two multivariable analyses were conducted to evaluate factors associated with seropositivity.

RESULTS

A total of 2864 participants were enrolled, of which 95/2167 (4.4%) participants were S-seropositive in phase 1 across all ages, and 61/697 (8.8%) unvaccinated children aged under ten years were S-seropositive in phase 2. Overall, South Asian participants had a higher seropositivity than other ethnicities (13.5% vs. 5.2%). Of 156 seropositive participants in both phases, 120 had no prior positive SARS-CoV-2 test. Young infants and young adults had the highest reported seropositivity rates (7.0% and 7.2% respectively vs. 3.0-5.6% across other age groups).

CONCLUSION

SARS-CoV-2 seropositivity among unvaccinated children and young adults was low in May 2022, and South Asians were disproportionately infected. This work demonstrates the need for improved diagnostics and reporting strategies that account for age-specific differences in pandemic dynamics and acceptability of testing mechanisms.
Knowledge, Stigma and Prevalence of HBV among two populations from Nepal: a cross-sectional study
Authors: Hogan Sam , McBride Kate A , Dixit Sameer , Page Andrew
Published: August 2023

Background

Hepatitis B virus (HBV) remains a public health issue in many developing nations, including Nepal. In Nepal the vaccination program was implemented in 2002-3 and aimed to reduce national prevalence of HBV. This study investigated socio-demographic, behavioural, and health service factors associated with HBV infection in low (Pokhara) and high (Dolpa) prevalence populations.

Methods

A serosurvey of 400 participants from within each population was conducted (final N = 799). The study combined a blood-draw to ascertain HBV status and a questionnaire that included demographic questions and items on knowledge of HBV, behavioural, and social factors associated with the risk of HBV infection. The blood draws were used to confirm HBV status as well as identify any previous infections from which participants may have recovered.

Results

There were 8/399 (2.01%, 95% CI 0.87%, 3.91%) current HBV infections among participants from Dolpa, compared with 2/400 (0.5%, 95% CI0.06%, 1.79%) among participants from Pokhara. The average age of each of the cohorts was relatively high, indicating an unclear association between vaccination programs and the low prevalence observed in this study. There was evidence from both sites there had been previous infections within the community as many of the participants indicated some level of protection from HBV either through vaccination or past infection (Dolpa 58/399, Pokhara 21/400) and recent cases who had recovered (Dolpa 4/399, Pokhara 3/400). Due to the relatively low prevalence of active cases of HBV, no meaningful associations between demographic, behavioural, and healthcare factors could be calculated. In both samples low level of knowledge of HBV and stigma towards people with HBV was evident.

Conclusions

This study found a low prevalence of HBV infection in both low and putatively high prevalence populations. However, knowledge of how HBV can be spread was quite low in each of the groups, indicating participants are managing to avoid infections while not necessarily being cautious around behaviours representing the greatest infection risk. There was also evidence of stigma being associated with having an active HBV infection, which may reduce the willingness of individuals to seek diagnosis or treatment.
Alterations in pathogen-specific cellular and humoral immunity associated with acute peripheral facial palsy of infectious origin
Authors: Mohammad Leyla , Fousse Mathias , Wenzel Gentiana , Flotats-Bastardas Marina , Faßbender Klaus , Dillmann Ulrich , Schick Bernhard , Zemlin Michael , Gärtner Barbara C. , Sester Urban , Schub David , Schmidt Tina , Sester Martina
Published: August 2023

Background and Objectives

Peripheral facial palsy (PFP) is a common neurologic symptom which can be triggered by pathogens or autoimmunity as well as trauma, tumors, cholesteatoma and further local conditions disturbing the peripheral section of the nerve. In general, its cause is often difficult to identify, remaining unknown in over two thirds of cases. As we have previously shown that the quantity and quality of pathogen-specific T cells change during active infections, we hypothesized that such changes also may help to identify the causative pathogen in PFPs of unknown origin.

Methods

Pathogen-specific T cells were quantified in blood samples of 55 patients with PFP and 23 healthy controls after stimulation with antigens from varicella-zoster virus (VZV), herpes-simplex viruses (HSV) or borrelia. T cells were further characterized by expression of the inhibitory surface molecule CTLA-4, and markers for differentiation (CD27) and proliferation (Ki67). Pathogen-specific antibody responses were analyzed using ELISA. Results were compared with conventional diagnostics.

Results

Patients with PFP were more often HSV-seropositive than controls (p=0.0003), whereas VZV-and borrelia-specific antibodies did not differ between groups. Although the quantity and general phenotypical characteristics of antigen-specific T cells did not differ either, expression of CTLA-4 and Ki67 was highly increased in VZV-specific T cells of 9 PFP patients, of which 5 showed typical signs of cutaneous zoster. In the remaining 4 patients, a causal relationship with VZV was possible but remained unclear by clinical standard diagnostics. A similar CTLA-4- and Ki67-expression profile was also found in a patient with acute neuroborreliosis.

Discussion

In conclusion, the high prevalence of HSV-seropositivity among PFP-patients may indicate an underestimation of HSV-involvement in PFP, even though HSV-specific T-cell characteristics seem insufficient to identify HSV as a causative agent. In contrast, striking alterations in VZV- and borrelia-specific T-cell phenotype and function may allow identification of VZV- and borrelia-triggered PFPs thus bearing the potential to improve specificity of the clinical diagnosis.
A non-canonical mechanism of GPCR activation
Authors: Powers Alexander S. , Khan Aasma , Paggi Joseph M. , Latorraca Naomi R. , Souza Sarah , Di Salvo Jerry , Lu Jun , Soisson Stephen M. , Johnston Jennifer M. , Weinglass Adam B. , Dror Ron O.
Published: August 2023

The goal of designing safer, more effective drugs has led to tremendous interest in molecular mechanisms through which ligands can precisely manipulate signaling of G-protein-coupled receptors (GPCRs), the largest class of drug targets. Decades of research have led to the widely accepted view that all agonists—ligands that trigger GPCR activation—function by causing rearrangement of the GPCR’s transmembrane helices, opening an intracellular pocket for binding of transducer proteins. Here we demonstrate that certain agonists instead trigger activation of free fatty acid receptor 1 by directly rearranging an intracellular loop that interacts with transducers. We validate the predictions of our atomic-level simulations by targeted mutagenesis; specific mutations which disrupt interactions with the intracellular loop convert these agonists into inverse agonists. Further analysis suggests that allosteric ligands could regulate signaling of many other GPCRs via a similar mechanism, offering rich possibilities for precise control of pharmaceutically important targets.
Lymphotoxin-β Promotes Bone Colonization and Osteolytic Outgrowth of Indolent Bone Metastatic cells of Breast Cancer
Authors: Wang Xuxiang , Zhang Tengjiang , Zheng Bingxin , Lu Youxue , Liang Yong , Xu Guoyuan , Zhao Luyang , Tao Yuwei , Song Qianhui , You Huiwen , Hu Haitian , Li Xuan , Sun Keyong , Li Tianqi , Zhang Zian , Wang Jianbin , Lan Xun , Pan Deng , Fu Yang-Xin , Yue Bin , Zheng Hanqiu
Published: August 2023

Bone metastatic relapse is a lethal consequence of breast cancer, occurring years after initial diagnosis. By analyzing single-cell transcriptomes of bone-seeding tumor cells andin vivobarcoded cDNA library screening, LTβ (lymphotoxin-β) is identified as a key factor highly expressed in early-stage bone metastatic cells, associated with poor bone metastasis-free survival, and capable of promoting dormancy reactivation in multiple breast cancer models. Mechanistically, tumor-derived LTβ activates NF-κB2 signaling in osteoblasts to express CCL2/5, facilitating tumor cell seeding and accelerating osteoclastogenesis. Both processes contribute to the reactivation of dormancy and metastatic outgrowth. Blocking LTβ signaling with a decoy receptor significantly suppressed bone colonization and metastatic progression, whereas clinical sample analysis revealed significantly higher LTβ expression in bone metastases than in primary tumors. Our findings highlight LTβ as a bone niche-induced factor that promotes tumor cell seeding and dormancy reactivation, underscoring its potential as a therapeutic target for preventing bone metastatic relapse in patients with breast cancer.
Genotype x Environment interaction and the evolution of sexual dimorphism: adult nutritional environment mediates selection and expression of sex-specific genetic variance inD. melanogaster
Authors: De Lisle Stephen P.
Published: August 2023

Sexual conflict plays a key role in the dynamics of adaptive evolution in sexually reproducing populations, and theory suggests an important role for variance in resource acquisition in generating or masking sexual conflict over fitness and life history traits. Here, I used a quantitative genetic genotype x environment experiment inDrosophila melanogaster, to test the theoretical prediction that variance in resource acquisition mediates variation in sex-specific component fitness. Holding larval conditions constant, I found that adult nutritional environments characterized by high protein content resulted in reduced survival of both sexes compared to an environment of lower protein content, and lower male reproductive success. Despite reduced mean fitness of both sexes in high protein environments, I found a sex*treatment interaction for the relationship between resource acquisition and fitness; estimates of the adaptive landscape indicate males were furthest from their optimum resource acquisition level in high protein environments, and females were furthest in low protein environments. Expression of genetic variance in resource acquisition and survival was highest for each sex in the environment it was best adapted to, although the treatment effects on expression of genetic variance eroded in the path from resource acquisition to total fitness. Cross-sex genetic correlations were strongly positive for resource acquisition, survival, and total fitness, and negative for mating success, although estimation error was high for all. These results demonstrate that environmental effects on resource acquisition can have predictable consequences for the expression of sex-specific genetic variance, but also that these effects of resource acquisition can erode through the life history.